JP2010030931A - Skin care preparation for external use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for preventing the occurrence of melanogenesis after ultraviolet irradiation without performing a physical treatment method that imposes heavy burden on the skin such as a laser or chemical peeling treatment. <P>SOLUTION: The method for preventing the occurrence of pigmentation after ultraviolet irradiation comprises using a skin care preparation for external use comprising one or two or more selected between (1) a component selected from among triterpene acid, a derivative thereof and/or a salt thereof and (2) an antioxidant. Preferably, the antioxidant is: vitamin A, a derivative thereof and a salt thereof; vitamin B, a derivative thereof and a salt thereof; a vitamin D, a derivative thereof and a salt thereof; vitamin E, a derivative thereof and a salt thereof; dibutylhydroxytoluene, butylhydroxyanisole and a salt thereof; ferulic acid, caffeic acid; and the like. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a skin external preparation such as cosmetics (including quasi-drugs), and more particularly to a skin external preparation suitable for cosmetics useful for preventing pigmentation.

Appropriate exposure to ultraviolet rays has been considered important for the body by activating the immune system to increase the resistance of the whole body or skin and improving blood circulation. However, exposure to excessive UV rays has been shown to lead to skin cancer caused by genetic mutations, including samban, which is an inflammation accompanied by blisters (blisters). It is supposed to be. In addition, exposure to ultraviolet rays causes pigmentation that appears to be localized or inhomogeneous, causing liver spots and senile pigment spots that impair the beauty of the appearance. Yes.

For the treatment of wrinkles and spots such as liver spots and senile pigment spots that are generated or deteriorated by exposure to ultraviolet rays, in addition to medical treatment methods such as laser or chemical peeling, tranexamic acid, vitamin C derivatives, Ascorbic acid, arbutin, kojic acid and the like are used as internal or external preparations (see, for example, Patent Document 1). Laser treatment or chemical peeling is expected as an effective treatment method for wrinkle and stain treatment, but it has been reported that symptoms worsen due to poor physical condition of the patient. Recently, there are some medical institutions that refrain from these treatment methods because the burden on patients' normal skin is large. Further, in the treatment aimed at improving pigmentation using the whitening agent, although a certain therapeutic effect is recognized, even if any whitening agent is used, it is a severe pigmentation by a single treatment, a stain, Or the effect of making a wrinkle inconspicuous, which is a change in three-dimensional shape, is not recognized. For severe spots and wrinkles that are difficult to treat, there are physical treatment methods such as laser treatment combined with treatment methods that use chemical substances or treatment methods that combine multiple chemical substances. Although being implemented, at present, further improvement of the therapeutic effect is desired.

  Triterpenic acids such as ursolic acid, oleic acid and derivatives thereof are wrinkle improving / skin-beautifying (for example, see Patent Document 2), antioxidant action, melanin production inhibitory action (for example, see Patent Document 3), Techniques that exhibit various biological activities such as inflammatory effects and are incorporated into external preparations for skin such as cosmetics are known. In particular, ursolic acid has undergone structural transformation aimed at improving solubility in oily or aqueous components, and these derivatives are known to exhibit various biological activities. Phosphorylated ursolic acid obtained by phosphorylating one of the hydroxyl groups of ursolic acid is a compound having significantly improved solubility in oily or aqueous components as compared with ursolic acid. And a rough skin improving action (see, for example, Patent Document 5). However, it is not known to use such a component in combination with a component having an antioxidant action, and it is not known that a synergistic effect with the whitening component can be obtained by such a combination.

  Antioxidant action has been confirmed in compounds having various chemical structures, and is incorporated not only in industrial products but also in various products such as foods and cosmetics for the purpose of preventing product deterioration. Furthermore, the compound having an antioxidant action is an injury to tissues, cells, genes and the like caused by active oxygen (for example, see Non-Patent Document 1), a melanin production inhibitory effect (for example, see Patent Document 6), an anti-inflammatory action It is known to exhibit various biological activities represented by preventing (see, for example, Non-Patent Document 2). In particular, the natural product α-tocopherol (vitamin E) derivative contained in plants has been clarified in connection with being an essential factor for reproductive function, and various studies have been conducted. It has been proven to have high antioxidant activity and safety, and is now widely used in foods and cosmetics.

  Antioxidants are formulated as an active ingredient that is expected to be effective and effective in cosmetics and quasi-drugs, and are intended for spots and wrinkles such as liver spots and senile pigment spots that are generated or worsened by ultraviolet irradiation. The treatment that we did is carried out. In addition, the above-mentioned medical treatment methods such as laser treatment or a combination of chemical peeling and a topical skin preparation containing an antioxidant have been implemented, but severe spots and wrinkles were noticeable. It is not recognized as effective.

  On the other hand, a topical skin preparation containing terpenic acid, a derivative thereof and an antioxidant is not known, and it is administered immediately after being irradiated with ultraviolet rays for the purpose of preventing pigmentation due to sunburn. In addition, it suppresses the occurrence of pigmentation itself by using such a form of use, and enables pigmentation by ultraviolet irradiation without significant burden on the skin such as chemical peeling or laser treatment. There is no known suppression.

JP-A-5-139950 JP-A-11-005727 JP-A-9-143050 WO2006132033 JP 2007-24464A Japanese Patent Laid-Open No. 06-072845 Development technology for anti-aging, whitening and moisturizing cosmetics, CMC Publishing, supervised by Masato Suzuki Paula Grammas, Landan Hamdheydari et. Al., Bioorg. Med. Chem., 319, 1047-1052, 2004).

The present invention has been made under such circumstances, and provides a means for preventing the occurrence of pigmentation after ultraviolet irradiation.

In view of such circumstances, the present inventors have prevented the occurrence of pigmentation after ultraviolet irradiation without performing a physical treatment with a heavy burden on the skin such as laser or chemical peeling treatment. As a result of earnest efforts, 1) a component selected from triterpenic acid, triterpenic acid derivatives and salts thereof, and 2) an external preparation containing an antioxidant is excellent in such action. And found out that the invention was completed. That is, the present invention is as follows.
<1> 1) a topical skin containing 1 or 2 or more selected from 1) a component selected from triterpenic acid, a derivative thereof and / or a salt thereof; and 2) an antioxidant. Agent.
<2> The skin external preparation according to <1>, wherein the triterpenic acid derivative is obtained by phosphorylating at least one hydroxyl group of triterpenic acid.
<3> The external preparation for skin according to claim 1 or 2, wherein the triterpenic acid derivative is ursolic acid and / or a salt thereof.
<4> The antioxidants include vitamins A, derivatives thereof and salts thereof, vitamins B, derivatives thereof and salts thereof, vitamins D, derivatives thereof and salts thereof, vitamins E, derivatives thereof and the like. <1> to <4>, which are one or more selected from the following salts: dibutylhydroxytoluene and butylhydroxyanisole and salts thereof, ferulic acid and caffeic acid, derivatives thereof and salts thereof The external preparation for skin according to any one of the above.
<5> The external preparation for skin according to <4>, wherein the antioxidant is tocophenol.
<6> The external preparation for skin according to <5>, wherein the tocopherol is δ-tocopherol.
<7> 0.001% by mass to 5% by mass of the ursolic acid, a derivative thereof and / or a salt thereof with respect to the total amount of the external preparation for skin, any of <1> to <6> The external preparation for skin according to any one of the above.
<8> The skin external preparation according to any one of <1> to <7>, wherein the antioxidant is contained in an amount of 0.001% by mass to 10% by mass with respect to the total amount of the external preparation for skin.
<9> Any one of <1> to <8>, wherein α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine is contained with respect to the total amount of the external preparation for skin. The skin external preparation described in 1.
<10> The external preparation for skin according to any one of <1> to <9>, which is a cosmetic (including quasi-drugs).
<11> The topical skin preparation according to any one of <1> to <10>, which is to be administered immediately after receiving ultraviolet irradiation for the purpose of preventing pigmentation due to sunburn.

According to the present invention, it is possible to provide means for preventing the occurrence of pigmentation after ultraviolet irradiation.

(1) Triterpenic acid and triterpenic acid derivative, which are essential components of the skin external preparation of the present invention The skin external preparation of the present invention contains a component selected from triterpenic acid, a derivative thereof and / or a salt thereof as an essential component. It is characterized by that. The triterpenic acid derivative can be applied without particular limitation as long as it is used in the field of skin external preparations such as cosmetics, and examples thereof include ursolic acid, oleanolic acid, and betulinic acid. Of these, ursolic acid is particularly preferred. Examples of the triterpenic acid derivative include triterpenic acid esters and amides. Among them, ursolic acid hydrocarbon ester having 1 to 20 carbon atoms or ursolic acid phosphoric acid ester is particularly preferable. It can illustrate suitably. Examples of the hydrocarbon ester having 1 to 20 carbon atoms include fats such as methyl ester, ethyl ester, hexyl ester, cyclohexyl ester, octyl ester, isooctyl ester, lauryl ester, cetyl ester, stearyl ester, isostearyl ester, and oleyl ester. Preferred examples include hydrocarbon group esters having aromatic rings such as aromatic esters, benzyl esters, and phenethyl esters. Such a component can be derived from ursolic acid according to a conventional method such as reacting a halogenated hydrocarbon in the presence of an alkali. The triterpenic acid ester is obtained by using a commercially available triterpenic acid as a starting material, converting it to a sodium salt using sodium hydride, and then reacting a halogenated hydrocarbon. For example, triterpenic acid phosphate is obtained by treating commercially available triterpenic acid with 1 to 3 equivalents of diethyl-N, N-diethyl phosphoramidate in the presence of tetrazole to convert t-butyl hydroperoxide. After reacting to make methyl phosphate of triterpenic acid, it can be further synthesized by acting trimethylsilyl bromide. These salts can be used without 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 metals 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 alginic acid salt. Such an ingredient exhibits an anti-inflammatory action, a melanin production inhibitory action, an action of promoting the reconstruction of the collagen fiber bundle structure by light irradiation, and the like for the skin. Working together with the agent, the damage received by the skin by the irradiation of ultraviolet rays is erased before inflammation occurs, and the effect of preventing serious symptoms from appearing is achieved. In order to achieve such an effect, the total amount of one or more selected from the above-mentioned triterpenic acid, derivatives thereof and / or salts thereof is 0.001% by mass to 5% by mass. Is preferable, and it is more preferable to contain 0.1 mass%-3 mass%. This is because if the amount is too small, the above-described effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

(2) Antioxidant as an essential component of the skin external preparation of the present invention The skin external preparation of the present invention is characterized by containing an antioxidant. Antioxidants include vitamins A, their derivatives and their salts, vitamins B, their derivatives and their salts, vitamins D, their derivatives and their salts, vitamins E, their derivatives and their salts, Examples include dibutylhydroxytoluene and butylhydroxyanisole and salts thereof, ferulic acid and caffeic acid, derivatives and salts thereof, among which α, β, γ, δ-tocopherol and the like The salt of can preferably be illustrated. Most preferred among these tocopherols are δ-tocopherol and its salts. Examples of physiologically acceptable salts include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, organic amine salts such as triethanolamine and triethylamine, ammonium salts, and arginine. Preferred examples include basic amino acid salts such as lysine and the like. Such an ingredient exhibits an antioxidant action, an anti-inflammatory action, a melanin production inhibitory action, etc. on the skin, but in the external preparation for skin of the present invention, it works together with the above-mentioned triterpenic acid and triterpenic acid derivative and is irradiated with ultraviolet rays. The damage received by the skin is erased before inflammation occurs, and the effect of preventing serious symptoms from occurring is achieved. In order to exhibit such an effect, it is preferable to contain 0.001% by mass to 10% by mass in total of one or more selected from the above antioxidants. It is more preferable to contain 0.01 mass%-5 mass%. This is because if the amount is too small, the above-described effect may not be achieved, and if the amount is too large, the effect may reach its peak and the degree of freedom of the system may be impaired.

(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 usually administered externally to the skin, such as cosmetics containing quasi-drugs, external preparations for skin, sundries for skin use, etc. Preferred examples can be given. Among these, cosmetics are particularly preferable. This is because, in cosmetics, reachability to the dermis is desired, and there are many active ingredients that are difficult to reach the dermis. Preferred examples of such cosmetics include lotions such as cosmetics, emulsions, essences, creams, pack cosmetics, facial cleansing cosmetics, cleansing cosmetics and the like. Further, the dosage form is not particularly limited as long as it is known in the cosmetics field, and is preferably exemplified for lotion preparations, oil-in-water preparations, water-in-oil emulsion preparations, composite emulsion emulsion preparations and the like. it can.

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, palm oil, palm oil, liquid Lanolin, hydrogenated palm oil, hydrogenated oil, molasses, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax and other oils, waxes; liquid paraffin, squalane, pristane, ozokerite, Hydrocarbons such as paraffin, ceresin, petrolatum, 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 -Le, Isosteari Higher alcohols such as alcohol, behenyl alcohol, octyl decanol, myristyl alcohol, cetostearyl alcohol; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, sebacic acid Di-2-ethylhexyl, cetyl lactate, diisostearyl malate, ethylene glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, glycerin tri-2-ethylhexanoate Synthetic ester oils such as trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentane erythritol tetra-2-ethylhexanoate; dimethylpolysiloxane, methylphenylpoly Chain polysiloxanes such as Loxane and diphenylpolysiloxane; Cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and dodecamethylcyclohexanesiloxane; Amino-modified polysiloxane, polyether-modified polysiloxane, and alkyl-modified polysiloxane , Oil agents such as silicone oils such as modified polysiloxane such as fluorine-modified polysiloxane; anionic surfactants such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, triethanolamine alkyl sulfate ; Cationic surfactants such as stearyltrimethylammonium chloride, 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 (such as glyceryl monostearate), propylene glycol fatty acid esters (such as propylene glycol monostearate), hardened castor oil derivatives, glycerin alkyl ether POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbite fatty acid esters (POE-sorbitol monolaurate, etc.), POE glycerin fatty acid ester Tells (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, Non-ionic surfactants such as hydrogenated castor oil derivatives (POE castor oil, POE hydrogenated castor oil, etc.), sucrose fatty acid ester, alkyl glucoside; polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol , Sorbitol, xylitol, maltitol, propylene Ricol, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4-hexanediol, 1,2-hexanediol, 1,2-octanediol, etc. Moisturizing ingredients such as sodium pyrrolidone carboxylate, lactic acid, sodium lactate; surface treated mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, silicic anhydride (Silica), powders such as aluminum oxide and barium sulfate; inorganic pigments such as bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, zinc oxide, which may be treated on the surface PAR; agents whose surface may be treated, such as titanium mica, fish phosphorus foil, bismuth oxychloride; red 202 which may be laked, red Color 228, Red 226, Yellow 4, Blue 404, Yellow 5, Red 505, Red 230, Red 223, Orange 201, Red 213, Yellow 204, Yellow 203, Blue 1 No., green 201, purple 201, red 204, etc .; organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, organopolysiloxane elastomer; paraaminobenzoic acid UV absorbers; Anthranilic acid UV absorbers; salicylic acid UV absorbers; cinnamic acid UV absorbers; benzophenone UV absorbers; sugar UV absorbers; 2- (2′-hydroxy-5′-t-octylphenyl) UV absorbers such as benzotriazole and 4-methoxy-4'-t-butyldibenzoylmethane; lower grades such as ethanol and isopropanol Alcohols; vitamin A or derivatives thereof, vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or a derivative thereof, vitamin B such as vitamin B12, vitamin B15 or a derivative thereof; Preferable examples include vitamins such as vitamin H, pantothenic acid, panthetin, and pyrroloquinoline quinone; and antibacterial agents such as phenoxyethanol.

  Among such optional components, α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine is particularly preferable. Such a component may contain a free form or a salt form. These salts can be used without any particular limitation as long as they are used in skin external preparations, for example, alkali salts such as sodium salts and potassium salts, calcium salts, magnesium salts, etc. Preferred examples include alkaline earth metal salts, ammonium salts, triethylamine salts, triethanolamine salts, organic amine salts such as monoethanolamine salts, and basic amino acid salts such as lysine salts and alginates. Moreover, as long as it is a salt with an acid, mineral acid salts, such as hydrochloride, phosphate, sulfate, and nitrate, and organic acid salts, such as carbonate, citrate, and tartrate, can be preferably exemplified. 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. As an elution solvent for silica gel column chromatography, a chloroform-methanol mixed liquid system can be preferably exemplified. The structure of such α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine is shown in Formula 1. In addition, as a salt of such a component, any salt used in an external preparation for skin can be used without any particular limitation. For example, alkali metal salts such as sodium salt and potassium salt, alkaline earth such as calcium salt and magnesium salt, etc. Preferred examples include metal amine salts, ammonium salts, triethylamine salts, triethanolamine salts, organic amine salts such as monoethanolamine salts, and basic amino acid salts such as lysine salts and alginates. Α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine can be produced and used by the above method, but diα, ε-bis (γ-N- (carbon number). 10-30) 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; α, ε-bis (γ-N-lauroylglutamyl) lysine) can be preferably exemplified. In addition, such a component can easily form a lipid bilayer membrane dispersion system (vesicle; nisome), and by including one or both of the essential components in such a form, the reachability of the skin can be improved. I can do it. In order to exert such an action, the total amount of one or more selected from α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine is used for the total amount of vesicles. On the other hand, it is preferable to contain 1% by mass, more preferably 5% by mass, and 50% by mass as the upper limit, and more preferably 10% by mass. This is because there may be a case where a stable vesicle is not formed when there are too many or too few components. In the form of a vesicle, an active ingredient having a hydrophobic portion is contained between the lipid biphasic phases, and the affinity between the outer side of the biphasic layer and the stratum corneum is used as a transporter that allows the active ingredient to reach the dermis. I can work. At this time, α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine itself also has a function of strengthening the barrier structure in the dermis, so the double effect of the vesicle material and the active ingredient Play. In the external preparation for skin of the present invention, the α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine may be contained in the form of vesicles, or in a form compatible with the oil phase. It can also be contained. When contained in a form compatible with the oil phase, the preferred content of α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine is 0 with respect to the total amount of the external preparation for skin. 0.01 to 10% by mass, and more preferably 0.05 to 5% by mass. Even when it is contained in the form of a vesicle, this content is followed, and it is preferable to adjust the blending amount of the vesicle so as to be within the range of the content. The α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine thus obtained has an affinity for the stratum corneum component, and because of this property, it is an active ingredient in a skin external preparation. Work as an excellent vehicle. In such an encapsulated form, it is preferable to encapsulate ursolic acid and ursolic acid derivative having a small content among the essential two components. In order to create an encapsulated nitrosome, it is preferable that ceramides coexist for the purpose of reinforcing the lipid bilayer membrane. Other than ceramides, phytosterols such as sitosterol and campesterol, (poly) glycerin fatty acid esters such as diglycerin monooleate, polyhydric alcohols such as glycerin And the like can be preferably exemplified as the iosome-forming component.

式１（但し、式中Ｒ１、Ｒ２はそれぞれ独立に炭素数１０〜３０のアシル基を表す。）

Formula 1 (wherein R 1 and R 2 each independently represents an acyl group having 10 to 30 carbon atoms)

As the ceramide, it is known that there are usually seven types of type 1 to type 7, and any of them can be used. Among them, type 2 is particularly preferable, and N-stearoyl dihydroxysphingosine is particularly preferable. Such ceramides have commercial products, and such commercial products can be purchased and used. Among such commercially available products, as a good example, “Ceramide I” (Cosmo Farm Co., Ltd.), which is type 1, N- (27-octadecanoyloxy-heptacosanoyl-)-phytosphingosine, is used. ), “Ceramide TIC-001” (manufactured by Takasago Fragrance Co., Ltd.) containing N-stearoyl dihydroxysphingosine of type 2, and “Ceramide III” containing N-stearoyl phytosphingosine of type 3 ( "Ceramide IIIA" (manufactured by Cosmo Farm), type 3 N-linoleoylphytosphingosine (Cosmo Farm), type 3 N-oleoyl phytosphingosine "Ceramide IIIB" (Cosmo Farm), type 6 N-2-hydroxystearoylphytosphingosine To, "Ceramide VI" (manufactured by Cosmo Pharm) and the like can be preferably exemplified. These can contain only the seed | species, and can also be made to contain in combination of 2 or more type. These can contain only the seed | species, and can also contain it in combination of 2 or more type. In the vesicle of the present invention, such a component has an action of reinforcing the vesicle structure produced by the α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine. In order to exhibit such an effect, it is preferable to contain 1% by mass, more preferably 5% by mass, and 50% by mass as an upper limit, and more preferably 10% by mass with respect to the total amount of vesicles. Even if there are too many such components, there may be cases where the above-mentioned effect is not achieved. The vesicle (Niosome) can be adjusted according to a conventional method using a microfluidizer or an extruder. The total content of ceramide is 10: 1 to 1:10 with respect to the total content of α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine. It is preferable that the ratio is 5: 1 to 1: 5.
The external preparation for skin of the present invention can be produced by treating the above-mentioned optional components and essential components according to a conventional method.

  Hereinafter, the present invention will be described in more detail with reference to examples.

  A vesicle dispersion was prepared according to the formulation shown below. That is, each of the components (a) and (b) is heated to 70 ° C. and dissolved uniformly, and while stirring, (a) is gradually added with (b), subjected to an extruder treatment to adjust the particle size, and a vesicle dispersion is obtained. It was. In the same manner, a comparative vesicle in which potassium ursolate phosphate was replaced with water was also prepared.

  Using the vesicle dispersion 1, a skin external preparation which is the skin external preparation of the present invention was prepared. That is, the emulsion which is the skin external preparation of this invention was produced according to the prescription shown below. That is, the components (A) were mixed and heated to 80 ° C. On the other hand, each component of (B) was heated to 80 degreeC. The mixture of (B) was added to the mixture of (A) and stirred to emulsify, and further (C) was added to neutralize, and then the mixture was stirred and cooled to 30 ° C. to prepare emulsion 1 (cosmetics). In the same manner, Comparative Example 1 in which vesicle dispersion 1 was replaced with comparative vesicle 1, Comparative Example 2 in which δ-tocophenol was replaced with water, vesicle dispersion in comparative vesicle 1 and δ-tocopherol Comparative Example 3 in which the water was replaced with water was also produced.

<Test Example 1>
The effect of preventing pigmentation was examined using a panel (n = 1) having the property of causing inflammation after ultraviolet irradiation and causing the inflammation site to cause pigmentation. That is, a 1.5 cm × 1.5 cm part is divided into two upper and lower parts on the inner side of the forearm, and a total of six parts are provided in three parts, and parts 1 to 5 are irradiated with ultraviolet rays twice the amount of minimal erythema (MED). For 1-4, 40 μL each of Emulsion 1 and Comparative Examples 1-3 were administered immediately after irradiation, with site 5 serving as an irradiation control and site 6 serving as an untreated control. 24 hours after irradiation, the degree of erythema was determined according to the criteria of drainage (-: no reaction, ±: false positive reaction, +: reaction with clear erythema, ++: reaction with edema), and 10 days thereafter Later, the difference in L value from an untreated site, which is an index of pigmentation, was measured with a Konica Minolta color difference meter CR400. The results are shown in Table 3. This confirmed the combined effect of potassium ursolate phosphate and δ-tocopherol. It can be seen that pigmentation can be suppressed by this combination effect.

<Test Example 2>
The effect of improving pigmentation was examined using a paneler (n = 1) having the property of causing inflammation after ultraviolet irradiation and causing the inflammation site to cause pigmentation. That is, a 1.5 cm × 1.5 cm part is divided into two upper and lower parts on the inner side of the forearm, and a total of six parts are provided in three parts, and parts 1 to 5 are irradiated with ultraviolet rays twice the amount of minimal erythema (MED). After confirming that the sites 1 to 5 were pigmented to the same extent after the day, 40 μL of the emulsion 1 and Comparative Examples 1 to 3 were respectively administered to the sites 1 to 4, and the site 5 was used as an irradiation control. Site 6 served as an untreated control. Seven days after sample administration, the difference in L value from the untreated site, which is an index of pigmentation, was measured with a Konica Minolta color difference meter CR400. The results are shown in Table 4. From this, it can be seen that no pigmentation improvement effect is observed in any sample.

  In the same manner as in Example 1, a dispersion 2 was prepared, and using this, an emulsion 2 (cosmetics) that was an external preparation for skin of the present invention was prepared. Evaluation according to Test Example 1 of this product showed an erythema level of ± and ΔL of 0.74.

  In the same manner as in Example 1, a vesicle dispersion 3 was prepared, and using this, an emulsion 3 (cosmetics), which is an external preparation for skin of the present invention, was prepared. Evaluation according to the test example of this product showed an erythema level of ± and ΔL of 0.62.

  Emulsion 4 (cosmetics) was produced with the same formulation combination as emulsion 1 and without making a vesicle dispersion. The evaluation according to Test Example 1 of this product was that the erythema level was + and ΔL was 0.90. It can be seen that it is preferable to use a vesicle dispersion.

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

Claims (11)

A skin external preparation characterized by containing one or more selected from 1) triterpenic acid, a derivative thereof and / or a salt thereof, and 2) an antioxidant. The external preparation for skin according to claim 1, wherein the triterpenic acid derivative is obtained by phosphorylating at least one hydroxyl group of triterpenic acid. The skin external preparation according to claim 1 or 2, wherein the triterpenic acid derivative is ursolic acid and / or a salt thereof. The antioxidants include vitamins A, derivatives thereof and salts thereof, vitamins B, derivatives thereof and salts thereof, vitamins D, derivatives thereof and salts thereof, vitamins E, derivatives thereof and salts thereof, 5. One or more selected from dibutylhydroxytoluene and butylhydroxyanisole and salts thereof, ferulic acid and caffeic acid, derivatives thereof and salts thereof, according to any one of claims 1 to 4. The skin external preparation as described. The external preparation for skin according to claim 4, wherein the antioxidant is tocophenol. The skin external preparation according to claim 5, wherein the tocopherol is δ-tocopherol. The ursolic acid, a derivative thereof and / or a salt thereof is contained in an amount of 0.001% by mass to 5% by mass with respect to the total amount of the external preparation for skin, according to any one of claims 1 to 6. Topical skin preparation. The skin external preparation according to any one of claims 1 to 7, wherein the antioxidant is contained in an amount of 0.001 mass% to 10 mass% with respect to the total amount of the external skin preparation. It contains α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine with respect to the total amount of the external preparation for skin, and the external preparation for skin according to any one of claims 1-8. Agent. It is a cosmetic (however, including a quasi-drug), The skin external preparation as described in any one of Claims 1-9 characterized by the above-mentioned. The skin external preparation according to any one of claims 1 to 10, which should be administered immediately after receiving ultraviolet irradiation for the purpose of preventing pigmentation due to sunburn.