JP2010030926A - Skin care preparation for external use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a more excellent means for preventing melanogenesis, more concretely, to provide an excellent skin care preparation for external use for preventing melanogenesis that can replace a laser treatment, chemical peeling or the like. <P>SOLUTION: The skin care preparation for external use comprises as its ingredient a combination of (1) a triterpene acid phosphate ester and/or a salt thereof and (2) a component selected from among glycyrrhetinic acid, an acid derivative thereof and/or a salt thereof. The employment of the constitution permits replacement of a laser treatment or chemical peeling by the cosmetic. <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 systemic or skin resistance and improving blood circulation. However, exposure to excessive UV rays has been shown to lead to skin cancer caused by genetic mutations, including inflammation of samban with blisters (blown bubbles), and more attention is paid to sun protection. It has become like. In addition, exposure to ultraviolet rays causes pigmentation that appears localized or inhomogeneous, and causes stains, wrinkles, liver spots, and senile pigment spots that impair the aesthetic appearance, and therefore prevent or treat them. Interest is high, especially among women.

For treatment of stains, wrinkles, liver spots, senile pigment spots, etc. that are generated or deteriorated by exposure to ultraviolet rays, in addition to physical treatment methods such as laser and 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 and chemical peeling are expected as effective treatment methods for spot or wrinkle treatment, but it has been reported that symptoms worsen due to poor physical condition of the patient, and in addition, normal treatment of patients Due to the heavy burden on the skin, some medical institutions have refrained from these treatment methods recently. In addition, in the treatment for pigmentation after ultraviolet irradiation using the above-described whitening agent, a certain therapeutic effect is observed, but in any use of the whitening agent, severe pigmentation is caused by single treatment, a stain, or The effect of making the wrinkles completely inconspicuous, which is a change in the three-dimensional shape, has not been recognized. For such pigmentation troubles that are difficult to treat, there is a combination therapy that carefully uses physical treatment methods such as laser treatment, or combines physical treatment methods with treatments with chemicals such as whitening agents. Although it has been implemented, the effect of preventing pigmentation troubles is not sufficient. In such a background, there is a need for better means for preventing pigmentation.

  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 anti-inflammatory action, and it is not known that a synergistic effect with the whitening component can be obtained by such a combination.

  Glycyrrhetinic acid and its derivatives are the main components of “liquorice”, a perennial plant that grows naturally in southern Siberia, western China and Eastern Europe, and as an anti-inflammatory analgesic, allergic rhinitis, rhinitis, gastric ulcer It is used for treatment. Other biological activities include anti-inflammatory action (see, for example, Patent Document 6), antiviral action (see, for example, Patent Document 7), and melanin production inhibitory effect (see, for example, Patent Document 8). In addition, skin roughness improving action (see, for example, Patent Document 9) is known, and application to cosmetics based on these activities is being made.

  Since glycyrrhetinic acid is not highly soluble in an aqueous component, various studies have been made to increase the solubility in an aqueous component by structure conversion and salt formation. In particular, dipotassium glycyrrhizinate in which a glycoside of glycyrrhetinic acid is a potassium salt is a compound with significantly improved solubility in aqueous components, and is widely used as a skin external preparation including cosmetics and quasi drugs. Yes.

In fact, this is a therapeutic single treatment or physical treatment method using a topical skin preparation containing dipotassium glycyrrhizinate, which treats spots and wrinkles such as liver spots and senile pigment spots that are generated or worsened by ultraviolet irradiation. -Combination treatment combined with the treatment has been carried out, but no effect has been observed to make severe spots / wrinkles inconspicuous.

  On the other hand, an external preparation for skin containing dipotassium glycyrrhizinate, ursolic acid, and derivatives thereof is not known, and this is administered immediately after being irradiated with ultraviolet rays for the purpose of preventing pigmentation due to sunburn. In addition, it is possible to suppress the occurrence of pigmentation itself by using such a mode, and without irradiating ultraviolet rays without a heavy burden on the skin such as chemical peeling or laser treatment. It is not known at all to suppress the pigmentation caused by.

JP-A-5-139950 JP-A-11-005727 JP-A-9-143050 WO2006132033 JP 2007-24464A JP-A-06-100451 JP-T-2006-527185 Japanese Patent Application Laid-Open No. 07-149622 Japanese Patent Laid-Open No. 06-135821

  The present invention has been made under such circumstances, and an object of the present invention is to provide a better means for preventing pigmentation. Specifically, it is intended to provide a superior external preparation for skin that can prevent pigmentation and can be substituted for laser treatment or chemical peeling.

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) containing a phosphate selected from triterpenic acid and / or a salt thereof, and 2) a component selected from glycyrrhetinic acid, an acid derivative thereof and / or a salt thereof. It was found that the external preparation for skin was excellent in such action, and the present invention was completed. That is, the present invention is as follows.
<1> 1) a topical skin containing 1) a phosphate of triterpenic acid and / or a salt thereof; and 2) a component selected from glycyrrhetinic acid, an acid derivative thereof and / or a salt thereof. Agent.
<2> The external preparation for skin according to <1>, wherein the triterpenic acid is ursolic acid.
<3> The external preparation for skin according to any one of <1> or <2>, wherein the glycyrrhetinic acid derivative is glycyrrhizic acid, stearyl glycyrrhetinate and / or a salt thereof.
<4> The phosphoric acid ester of triterpenic acid 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, any of <1> to <3> The external preparation for skin according to any one of the above.
<5> 0.001% by mass to 5% by mass of the glycyrrhetinic acid, a derivative thereof, and a salt thereof with respect to the total amount of the external preparation for skin, any one of <1> to <4> The skin external preparation described in 1.
<6> Any one of <1> to <5>, characterized by containing α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine with respect to the total amount of the external preparation for skin. The external preparation for skin according to Item.
<7> The external preparation for skin according to <6>, wherein the α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine forms a vesicle.
<8> The external preparation for skin according to any one of <1> to <7>, which is a cosmetic (however, including quasi-drugs).
<9> The external preparation for skin according to any one of <1> to <8>, which is used for preventing pigmentation.
<10> The external preparation for skin according to any one of <1> to <9>, which is used immediately after ultraviolet irradiation.

  The external preparation for skin of the present invention is excellent in the effect of preventing pigmentation. By using the external preparation for skin of the present invention immediately after ultraviolet irradiation, subsequent pigmentation can be sufficiently prevented.

(1) Triterpenic acid phosphate ester and / or salt thereof, which is an essential component of the skin external preparation of the present invention The skin external preparation of the present invention is selected from phosphoric ester of triterpenic acid and / or a salt thereof. A component is contained as an essential component. The phosphate of triterpenic acid has a structure in which at least one of the hydroxyl groups of triterpenic acid having a hydroxyl group is phosphorylated. The triterpenic acid having a hydroxyl group can be applied without particular limitation as long as it is used in the field of external preparations for skin such as cosmetics. For example, ursolic acid, oleanolic acid, betulinic acid Asian acids and the like can be preferably exemplified, and ursolic acid can be particularly preferably exemplified among these.

The phosphate ester of triterpenic acid can be obtained by phosphorylating triterpenic acid by a generally known method. For example, a phosphoric acid ester of ursolic acid is prepared by treating commercially available ursolic acid with 1 to 3 equivalents of diethyl-N, N-diethyl phosphoramidate in the presence of tetrazole. It can be synthesized by reacting butyl hydroperoxide to make methyl phosphate of ursolic acid and then further reacting with 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 components express an anti-inflammatory action, a melanin production-inhibiting action, a collagen fiber bundle structure restructuring promotion action by light irradiation, and the like on the skin. In the external preparation for skin of the present invention, glycyrrhetic acid described later Working together with the derivative, the damage received by the skin by ultraviolet irradiation is erased before inflammation occurs, and the effect of preventing serious symptoms from appearing is achieved. In order to exert such effects, the total amount of one or more selected from the phosphoric esters of triterpenic acid and / or their salts is 0.001% by mass to 5% by mass. It is preferable to contain 0.01% by mass to 3% by 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) Glycyrrhetic acid and glycyrrhetinic acid derivative, which are essential components of the external preparation for skin of the present invention, The external skin preparation of the present invention comprises a component selected from a glycyrrhetinic acid derivative and a salt thereof. Examples of the glycyrrhetinic acid derivative include glycyrrhizic acid glycoside glycyrrhizin, ester of glycyrrhizic acid, amide, acylated glycyrrhetinic acid, alkyl ether, and the like. Among these, glycyrrhizic acid and / or physiologically An acceptable salt can be preferably exemplified. 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. Most preferred among these salts is the potassium salt. This is because it is already known that there are many examples of use and safety is high. Such an ingredient exhibits an anti-inflammatory action, a melanin production inhibitory action, a rough skin improving action, etc. on the skin, but in the external preparation for skin of the present invention, it works together with the phosphate ester of triterpenic acid 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 achieve such an effect, it is preferable to contain one or more selected from the above-mentioned glycyrrhetinic acid, glycyrrhetinic acid derivatives and salts thereof in a total amount of 0.001% by mass to 5% by mass. . 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.

  Further, the content ratio (mass) of the phosphate ester of triterpenic acid and / or a salt thereof and glycyrrhetic acid, a glycyrrhetic acid derivative and / or a salt thereof is preferably 20: 1 to 1:20, more preferably 5 : 1-1: 5.

(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 derivatives thereof, vitamin B such as vitamin B12, vitamin B15 or derivatives thereof; α-tocopherol , Β-tocopherol, γ-tocopherol, vitamin E such as vitamin E acetate, vitamin D, vitamin H, pantothenic acid, panthetin, vitamins such as pyrroloquinoline quinone, etc .; phenoxyethanol, etc. The antibacterial agent is preferably exemplified.

  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.

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 content ratio (mass) of α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine and ceramide in the vesicle is preferably 5: 1 to 1: 5, more preferably 3: 1. ~ 1: 3.

In the external preparation for skin of the present invention, ursolic acid is preferable as triterpenic acid, and ursolic acid phosphate is particularly preferable.
Moreover, when the skin external preparation of this invention contains a vesicle, it is also preferable to make this vesicle contain glycerin fatty acid ester, polyglycerin fatty acid ester, pyroglutamic acid glycerin fatty acid ester. It is also preferable to contain phytosterol such as sitosterol.

  The skin external preparation of the present invention is preferably a skin external preparation for preventing pigmentation. In particular, it is preferable to use a skin external preparation for use immediately after the ultraviolet irradiation. This is because an excellent effect of preventing pigmentation can be obtained by combining the essential components. In particular, by using it immediately after ultraviolet irradiation, subsequent pigmentation can be extremely effectively prevented.

  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 of A and B is heated to 70 ° C. and dissolved uniformly, and under stirring, a is gradually added to B, and this is subjected to an extruder treatment to adjust the particle size to obtain a vesicle dispersion. 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 (A) 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 glycyrrhetinic acid was replaced with water, vesicle dispersion was replaced with comparative vesicle 1, and glycyrrhetinic acid was replaced with water. Comparative Example 3 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. From this, the combined effect of potassium ursolate phosphate and glycyrrhetinic acid was confirmed. 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, according to the following formulation, emulsion 2 (cosmetics), which is an external preparation for skin of the present invention, was prepared. The evaluation according to Test Example 1 was that the erythema level was ± and the ΔL value was 0.60. It was confirmed that the same effect was expressed with a glycyrrhetic acid derivative.

  Similarly to Example 1, vesicle dispersion 2 (Table 6) was prepared, and using this, emulsion 3 (cosmetics), which is an external preparation for skin of the present invention, was prepared. The evaluation according to Test Example 1 of this product was an erythema level of ± and a ΔL value of 0.91.

  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 an erythema level of ± and ΔL of 1.48. It can be seen that it is preferable to use a vesicle dispersion system.

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

Claims (10)

An external preparation for skin comprising 1) a phosphate ester of triterpenic acid and / or a salt thereof, and 2) a component selected from glycyrrhetinic acid, an acid derivative thereof and / or a salt thereof. The external preparation for skin according to claim 1, wherein the triterpenic acid is ursolic acid. The external preparation for skin according to claim 1 or 2, wherein the glycyrrhetinic acid derivative is glycyrrhizic acid, stearyl glycyrrhetinate and / or a salt thereof. The phosphoric acid ester of triterpenic acid 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 3. Topical skin preparation. It contains 0.001 mass%-5 mass% of the said glycyrrhetinic acid, its derivative (s), and their salts with respect to the skin external preparation whole quantity, The skin external application as described in any one of Claims 1-4 characterized by the above-mentioned. Agent. It contains α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine with respect to the total amount of the external preparation for skin, according to any one of claims 1 to 5, Skin external preparation. The external preparation for skin according to claim 6, wherein the α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine forms vesicles. The skin external preparation according to any one of claims 1 to 7, which is a cosmetic (however, including quasi-drugs). The external preparation for skin according to any one of claims 1 to 8, which is used for prevention of pigmentation. The skin external preparation as described in any one of Claims 1-9 for using immediately after ultraviolet irradiation.