JP4989119B2 - Skin external preparation suitable for vesicle system - Google Patents

Description

  The present invention relates to a skin external preparation, and more particularly to a skin external preparation suitable for a vesicle dispersion preparation.

  The role of the skin in the living body is the boundary that separates the body and the outside of the body, and therefore, it is an important protective organ that prevents foreign invasion from the outside. While such a protective function prevents the living body from entering a foreign body, it also prevents absorption of a medicinal component that is desired to be delivered transdermally, which is a pharmacokinetic obstacle. For this reason, it can be said that development of means for promoting transdermal absorption of various active ingredients has been desired. Examples of methods for promoting percutaneous absorption that have been studied so far include a method using the solvent effect of polyhydric alcohol (see, for example, Patent Document 1), and polyglycerin-modified silicone is used as a percutaneous absorption enhancer. There are a method (for example, see Patent Document 2), a method using a liposome (for example, see Patent Document 3), and the like. The liposome preparation is a means for mainly containing a water-soluble active ingredient in an inner aqueous phase surrounded by a phospholipid bilayer membrane and promoting percutaneous absorption of the water-soluble active ingredient. There is a vesicle dispersion system in which an oil-soluble active ingredient is contained between lipid bilayer membranes of vesicles that are particles of only lipid bilayer membranes having no phase (see, for example, Patent Document 4). This system can enhance the percutaneous absorption of oil-soluble active ingredients, but there are limitations on the lipids that form a stable vesicle dispersion, and it is applied to hair cosmetics such as rinses slightly. Only. This is because the surfactant that forms a stable vesicle dispersion is a cationic surfactant and is highly irritating to the skin when applied in a form that does not wash off transcutaneously. That is, it can be said that development of a vesicle dispersion preparation capable of transdermal administration is desired.

  On the other hand, α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine is a gemini-type surfactant and is commercially available as a cosmetic raw material, but it has a phosphorylcholine structure. It has never been known to form stable vesicle dispersions in the presence of polymers or copolymers. It is known that such a polymer or copolymer has a water retention effect and a supplement / strengthening effect of the stratum corneum barrier function based thereon (see, for example, Patent Document 5, Patent Document 6, and Patent Document 7), The vesicle stabilizing action of was not known at all. In addition, a skin external preparation in the form of a vesicle dispersion containing 1) α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine and 2) a polymer or copolymer having a phosphorylcholine structure. Is not known at all.

JP 2005-206570 A JP 2003-183117 A JP 2004-143080 A WO2004 / 004676 JP 2005-281253 A JP 2005-189011 A JP 2005-8592 A

  The present invention has been made under such circumstances, and an object of the present invention is to provide a vesicle dispersion preparation capable of transdermal administration.

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 vesicle-dispersed 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) said polymer or copolymers having a phosphorylcholine structure, polymethacryloylacetones oxyethyl 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 skin external preparation according to any one of (1) to (4), further comprising a saturated aliphatic higher alcohol .
(6) One or two or more types selected from the components shown in the following group A are contained in the dispersed vesicle, (1) to (5) Topical skin preparation.
(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

  According to the present invention, a vesicle dispersion preparation capable of transdermal administration can be provided.

(1) α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine which is an essential component of the external preparation for skin of the present invention is α, ε-bis (γ -N- (C10-30) acylglutamyl) lysine is contained as an essential component. Such a component may contain a free form or may be contained in the form of a salt. 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. The acyl group has 10 to 30 carbon atoms. Such an acyl group may be linear, branched or cyclic, and may be saturated or unsaturated. good. Specific examples of the acyl group include, for example, decanoyl group, lauroyl group, myristoyl group, palmitoyl group, stearoyl group, behenoyl group, isostearoyl group, oleoyl group, linoloyl group, etc. Particularly preferred. Α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine has two acyl groups, and the two acyl groups may be the same or different. May be. α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine can be produced, for example, by the following procedure. That is, glutamic acid is reacted with acyl chloride in the presence of an alkali such as triethylamine to obtain N-acyl glutamic acid. Thereafter, it can be produced by condensing lysine at a molar ratio of 2: 1 in the presence of a peptide synthesis reagent such as DCC. The reaction product thus obtained can be purified by silica gel column chromatography or the like. Preferred examples of the elution solvent for silica gel column chromatography include a chloroform-methanol mixed solution system. The structure of such α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine is shown in Formula 1.

Formula 1 (wherein, R 1 and R 2 each independently represents an alkyl group or an 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, 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.

(2) Polymer or copolymer having a phosphorylcholine structure, which is an essential component of the external preparation for skin of the present invention, is characterized in that it contains a polymer or copolymer having a phosphorylcholine structure. The polymer having a phosphorylcholine structure is preferably a polymer or copolymer having (meth) acryloyloxyethyl phosphorylcholine as a constituent monomer, and the copolymer is a copolymer with an ester of (meth) acrylic acid (having 4 to 20 carbon atoms). Can be suitably exemplified. Such polymers or copolymers already exist on the market, and such commercial products can be purchased and used. Examples of such commercially available products include “Lipidure HM” (manufactured by Nippon Oil & Fats Co., Ltd.), which is polymethacryloyloxyethyl phosphorylcholine, and “Lipidure PMB” (Nippon Oil Co., Ltd.) which is a methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer “Lipidure NR” (manufactured by NOF Corporation), which is a methacryloyloxyethyl phosphorylcholine / stearyl methacrylate copolymer, is a preferred example. Such a component may contain only one species, or may contain two or more species in combination. Such components have the effect of imparting stability to the formed vesicle dispersion. In order to express such an action, the polymer or copolymer having the phosphorylcholine structure is preferably contained in a total amount of 0.01 to 5% by mass, more preferably 0.05 to 1% by mass. . If the amount is too small, the above effects may not be achieved. If the amount is too large, the usability may be impaired, for example, stickiness or a feeling of coating may be felt after use. By containing such a component, the skin barrier function can be improved, and in combination with the moisturizing action of the aforementioned α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine, exceptional skin Improvement effects can also be realized as secondary effects.

(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 preferable content of the oil-soluble active ingredient is 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.

<Production Example 1>
2 l of 50% ethanol was added to 500 g of Lamiaceae rosemary leaves, heated to reflux for 3 hours, cooled to room temperature, filtered to remove insolubles, concentrated under reduced pressure, and lyophilized. This is dispersed in water, liquid-liquid extracted with 200 ml of normal hexane and 200 ml of 5% aqueous sodium hydroxide solution, the aqueous phase is taken, neutralized by adding 1N hydrochloric acid thereto, and ethyl acetate is added thereto to liquid-liquid. Extraction was performed, the ethyl acetate layer was taken, washed twice with water, and then concentrated under reduced pressure to obtain 16 g of Extract 1 containing 0.56M ursolic acid.

<Production Example 2>
1 L of 50% ethanol was added to 200 g of the above-ground part of Asteraceae Achillea millet, heated to reflux for 3 hours, cooled to room temperature, insolubles were removed by filtration, concentrated under reduced pressure, and lyophilized. This was liquid-liquid extracted with 200 ml of water and 200 ml of ethyl acetate, and then the ethyl acetate layer was taken and concentrated under reduced pressure. This was dispersed in water, charged to a column packed with Diaion HP-20, washed with 3 liters of water, washed with water, and then leached with 1 liter of ethanol to elute the adsorbate, and the elution solution was concentrated under reduced pressure. 3.8 g of extract 2 containing 0.73M of centauridine was obtained.

<Production Example 3>
2 l of 50% ethanol was added to 300 g of pulverized fruit of Acedaraceae, and the mixture was heated to reflux for 3 hours, cooled to room temperature, filtered to remove insolubles, concentrated under reduced pressure, and lyophilized. This was liquid-liquid extracted with 200 ml of water and 200 ml of ethyl acetate, and then the ethyl acetate layer was taken and concentrated under reduced pressure. This was dispersed in water, charged to a column packed with Diaion HP-20, washed with 3 liters of water, washed with water, and then leached with 1 liter of ethanol to elute the adsorbate, and the elution solution was concentrated under reduced pressure. 14.2 g of extract 3 containing 1.43M escin was obtained.

<Production Example 4>
500 ml of 50% ethanol was added to 100 g of lily family Bakumondo bulbs, heated under reflux for 3 hours, cooled to room temperature, filtered to remove insoluble materials, concentrated under reduced pressure, and then freeze-dried. This was liquid-liquid extracted with 200 ml of water and 200 ml of ethyl acetate, and then the ethyl acetate layer was taken and concentrated under reduced pressure. This was dispersed in water, charged to a column packed with Diaion HP-20, washed with 3 liters of water, washed with water, and then leached with 1 liter of ethanol to elute the adsorbate, and the elution solution was concentrated under reduced pressure. 2.1 g of extract 4 containing 0.45M of methyl ophiopogononone B was obtained.

<Production Example 5>
500 g of birch bark was cut into pieces, 2 l of 50% ethanol was added thereto, heated to reflux for 3 hours, cooled to room temperature, insolubles were removed by filtration, concentrated under reduced pressure, and lyophilized. This was liquid-liquid extracted with 200 ml of water and 200 ml of ethyl acetate, and then the ethyl acetate layer was taken and concentrated under reduced pressure. This was dispersed in water, charged to a column packed with Diaion HP-20, washed with 3 liters of water, washed with water, and then leached with 1 liter of ethanol to elute the adsorbate, and the elution solution was concentrated under reduced pressure. 7.5 g of Extract 5 containing 0.41 M betulinic acid and 0.94 M betulin was obtained.

  Moreover, in the external preparation for skin of this invention, since a vesicle dispersion system is employ | adopted suitably, since it has the effect | action which suppresses the association of this vesicle, it is preferable to contain a phospholipid or a ceramide. As the phospholipid, lecithin, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, or a lyso form thereof is preferable, and lysolecithin is particularly preferable. Such components include commercial products, and such commercial products can be purchased and used. For example, “Resinol SH50” (manufactured by Nippon Surfactant Co., Ltd.) can be exemplified. As the ceramide, any of types 1 to 7 can be suitably used, and types 2 to 3 are particularly preferable. As such a ceramide, a commercially available product exists, and such a commercially available product can be purchased and used. As such commercially available products, there are “Ceramide III”, “Ceramide IIIA”, “Ceramide IIIB”, etc. manufactured by Cosmo Farm as type 3 ceramides, and as type 2 ceramides, manufactured by Takasago International Corporation. “Ceramide TIC-100” exists, and as other types of ceramides, type 6 “Ceramide VI” (manufactured by Cosmo Farm), type 1 “Phytoceramide I” (manufactured by Cosmo Farm) and the like can be preferably exemplified. Such a component has an effect of improving the stability of the vesicle. In order to exhibit such an effect, the total amount of the component is changed to the α, ε-bis (γ-N- (C10-30). ) Acylglutamyl) It is preferably contained in a mass ratio of 1: 1 to 1: 100 with respect to the total amount of lysine. The total amount of the external preparation for skin is preferably 0.0005 mass as the lower limit. %, More preferably, it is 0.1 mass%, More preferably, it is 0.5 mass%. As an upper limit, Preferably it is 10 mass%, More preferably, it is 5 mass%, More preferably, it is 1 mass%. This is because if the amount is too small, the stability of the vesicle may not be maintained, and if it is too large, the vesicle may not be contained in the vesicle and may be precipitated as an insoluble matter. Moreover, considering the blending of ceramide into a skin external preparation from a different viewpoint, ceramide is a highly crystalline substance, and in an ordinary emulsification system, the upper limit of the blending is 0.05% by mass. It is said that the upper limit of the liquid crystal emulsion system of polyglycerin fatty acid ester and polyhydric alcohol which can contain the most ceramide is 0.3% by mass. On the other hand, in the vesicle dispersion which is a preferred form of the external preparation for skin of the present invention, ceramide can be contained in an amount of 0.5% by mass or more without causing crystals to precipitate.

  The skin external preparation of the present invention preferably contains a saturated aliphatic higher alcohol in order to stabilize the vesicle structure. Suitable examples of such higher alcohols include cetyl alcohol, stearyl alcohol, and behenyl alcohol. Such a component may contain only one species, or may contain two or more species in combination. The preferred content is preferably 0.1% by mass, more preferably 0.2% by mass as the lower limit, and more preferably 3% as the upper limit with respect to the total amount of the external preparation for skin. % By mass, more preferably 1% by mass.

  In the external preparation for skin of the present invention, from the viewpoint of strengthening the bimolecular association structure of the bilayer membrane of the vesicle, it is preferable to contain 10% by mass or more, more preferably 12% by mass or more of polyhydric alcohol. . The polyhydric alcohol is not particularly limited as long as it is used in a skin external preparation. For example, 1,3-butanediol, glycerin, diglycerin, dipropylene glycol, 1,2-pentanediol, 1 , 2-hexanediol, isoprene glycol, polyethylene glycol and the like. Such a component can contain only one species or a combination of two or more species. The upper limit of this component is the total amount, and is preferably 25% by mass and more preferably 20% by mass with respect to the total amount of the external preparation for skin.

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. Examples of such optional ingredients include 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, and hardened coconut oil. Oil, wax, oils such as beeswax, molasses, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax; , 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 acylmethyltaurine; sorbitan fatty acid esters (sorbitan) Monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (eg, glyceryl monostearate), propylene glycol fatty acid esters (eg, propylene glycol monostearate), 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 glycerol 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 derivatives (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 B 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; , Vitamins such as pantothenic acid, pantethine, etc .; phenoxyethanol, etc. Such as antimicrobial agents can be preferably exemplified.

  The external preparation for skin of the present invention can be produced by treating these components according to a conventional method. The external preparation for skin of the present invention is not particularly limited as long as it is externally applied to the skin. For example, basic cosmetics such as lotions, essences, emulsions, creams, packs, foundations, under-makeups, Makeup cosmetics such as control colors, highlights, UV protective cosmetics such as sun care milk and sun care cream, cleaning products such as rinses, shampoos, body shampoos, cosmetics for hair such as hair creams and hair packs, antifungals Skin external medicines, anti-inflammatory skin external medicines, steroid skin external medicines, external skin disinfectants, skin external goods, and the like can be suitably exemplified, among which cosmetics are preferable, and basic cosmetics are particularly preferable. In the basic cosmetics, the active ingredient can be efficiently transdermally absorbed, and the vesicle itself has a protective effect on the skin barrier function, and can suppress the increase in TEWL (transcutaneous water dispersion loss). .

  Hereinafter, the present invention will be described in more detail with reference to examples, but it goes without saying that the present invention is not limited to such examples.

  In accordance with the formulation shown below, a cosmetic that is an external preparation for skin of the present invention was prepared. That is, the ingredients of (a) and (b) were heated to 80 ° C., and (b) was gradually added to a under stirring, followed by stirring and cooling to obtain a milky cosmetic 1. It was revealed from observation with a polarizing microscope that the emulsion cosmetic was a vesicle dispersion. At the same time, Comparative Example 1 in which “Lipidure HM” was replaced with water and Comparative Example 2 in which “Perisea L-30” was replaced with decaglycerin monooleate were also produced.

  About the said cosmetics 1, the comparative example 1, and the comparative example 2, stability was investigated by the severe test. The severe test conditions were stored for 4 months in an aging box at 40 ° C. = − 10 ° C. This aging box keeps 40 ° C for 24 hours, then cools it down to -10 ° C over 24 hours, maintains it at -10 ° C for 24 hours, and then repeats the cycle of raising the temperature to 40 ° C over 24 hours. It is. After storage for the period, the sample was stored at 20 ° C. for 12 hours and observed. The observation items were the presence / absence of separation, the presence / absence of crystal precipitation, and the average particle diameter in five fields of view under the microscope. Since the comparative example 2 recognized the isolation | separation state of the transparent aqueous phase and the cloudy precipitation phase at the time of completion | finish of storage, these observations were not performed. The results are shown in Table 2. This shows that the cosmetic of the present invention is excellent in stability.

<Test Example 2>
The inhibitory effect of TEWL was examined using the inner forearm of the panel. The inner part of the forearm is stripped 15 times with surgical tape to create a rough skin of the model. Four 2cm x 4cm parts are created here, and TEWL is measured using "Tevameter" (integral). Then, after the treatment with each cosmetic, TEWL (unit: mg / cm ² ) was measured again at an interval of 10 minutes. One site served as an untreated control. The results are shown in Table 3. From this, it can be seen that cosmetic 1 which is an external preparation for skin of the present invention has an excellent TEWL suppressing effect.

  In the same manner as cosmetic 1 in Example 1, cosmetics 2 to 4 which are external preparations for skin of the present invention were produced according to the following formulation. The results of evaluation according to the method of Test Example 1 are shown in Table 5. It turns out that these have the same effect as cosmetics 1.

  In the same manner as the cosmetic 1 of Example 1, cosmetics 5 and 6 which are external preparations for skin of the present invention were produced according to the following formulation. The results of evaluation according to the method of Test Example 1 are shown in Table 7. It turns out that these have the same effect as cosmetics 1.

  In the same manner as the cosmetic 1 of Example 1, cosmetics 7 to 14 which are external preparations for skin of the present invention were produced according to the following formulation. The results of evaluation according to the method of Test Example 1 are shown in Table 9. It turns out that these have the same effect as cosmetics 1.

  The present invention can be applied to external preparations for skin such as cosmetics.

Claims (6)

1. A vesicle-dispersed skin external preparation containing 1) 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. The skin external preparation described in 1. In the polymer or the copolymer having a phosphorylcholine structure, polymethacryloylacetones oxyethyl phosphorylcholine, butyl methacrylate methacryloyloxyethyl phosphorylcholine Turkey lincomycin polymer, one or two or more kinds selected from stearyl methacrylate, methacryloyloxyethyl phosphorylcholine Turkey lincomycin polymers and salts thereof The external preparation for skin according to claim 1 or 2, wherein the preparation is external. Further characterized in that it contains the ceramide and / or phospholipid, skin external preparation according to any one of claims 1 to 3. The skin external preparation according to any one of claims 1 to 4 , further comprising a saturated aliphatic higher alcohol . The skin external application according to any one of claims 1 to 5, wherein the dispersed vesicle contains one or more selected from the components shown in the following group A. Agent.
(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