JP2007161610A - Cosmetic for improving skin barrier function - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a technique for quickly lowering the once increased TEWL (transepidermal water loss) to break out vicious cycle to the skin. <P>SOLUTION: The invention provides a skin care preparation containing (1) one or more compounds selected from ursolic acid, its salt and its ester and (2) a dimer acid diester. The one or more compounds selected from ursolic acid, its salt and its ester preferably contain benzyl ursolate, the dimer acid diester is preferably di(phytosteryl/isostearyl/cetyl/stearyl/behenyl) dimer dilinoleate, and the diester preferably further contains a polyhydric alcohol ester of alginic acid. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an external preparation for skin, and more particularly to an external preparation for skin suitable as a cosmetic.

  Ursolic acid is a kind of triterpenic acid, and ursolic acid or its ursolic acid derivatives such as methyl ester, stearyl ester, oleyl ester, and benzyl ester have various effects on the skin, and thus are useful raw materials for cosmetics. ing. Examples of the action on the skin include an action on dryness of the scalp (see, for example, Patent Document 1), a hair growth action (see, for example, Patent Document 2), an improvement effect on wrinkles (for example, see Patent Document 3), The effect | action with respect to a stress-related skin disease (for example, refer patent document 4) etc. are known.

  On the other hand, dimer acid diesters are viscous oily components developed as oily components to replace lanolin, which are difficult to use due to problems such as the possibility of developing sensitization, and are also excellent in water retention. (For example, refer to Patent Document 5 and Patent Document 6) Such components have the effect of improving the adhesion and moist feeling of oil gel cosmetics and emulsified cosmetics, and adding an excellent feel to the cosmetic dosage form. However, the combination of dimer acid diester and ursolic acid or its derivatives was not known at all, and this combination was synergistically significant for skin with enhanced transdermal water dispersion (TEWL). It was not known at all to have an improvement effect. In particular, TEWL, which is significantly enhanced under stress, usually takes a long time to recover, and its prognosis is not preferable, but the combination of dimer acid diester and ursolic acid or its derivative is as follows. As described, there was a significant improvement and there was no such report.

  On the other hand, skin disorders accompanied by a marked increase in TEWL is one of the phenomena that has been increasing rapidly in recent years. Along with a marked increase in TEWL, the skin barrier function is remarkably lowered, which further increases the sensitivity of the skin itself. It is a phenomenon of increasing. In the sensitive skin and chemical hypersensitivity fields which have been increasing in recent years, it is said that there are not a few cases in which symptoms deteriorated due to repeated vicious circles, starting from the above-mentioned decrease in barrier function. It is also said that one of the causes of the decrease in the skin barrier function that is the origin of this is a marked increase in the sympathetic nerve on the living body side against an excessively stressed state. Since the increase in TEWL also leads to further increase in sympathetic nerve, it is important for skin improvement to end this vicious circle, and the development of such a technique has been desired.

JP 2004-277406 A JP 2004-182627 A JP 2002-255781 A JP 2002-97135 A JP 2004-269396 A JP 2005-255525 A

  The present invention has been made under such circumstances, and it is an object of the present invention to provide a technique for quickly reducing TEWL once enhanced so that it does not form a vicious circle with respect to the skin.

In view of such a situation, the present inventors, as a result of repeated earnest research efforts, seeking a technique for rapidly reducing TEWL, which has been enhanced once, so as not to form a vicious circle on the skin, It has been found that an external preparation for skin containing 1) one or more selected from ursolic acid, a salt thereof and an ester thereof, and 2) a diester of dimer acid is excellent in such action, and has completed the invention. . That is, the present invention is as follows.
(1) A topical skin preparation comprising 1) one or more selected from ursolic acid, a salt thereof and an ester thereof, and 2) a diester of dimer acid.
(2) The skin external preparation according to (1), which contains at least benzyl ursolate as at least one selected from the ursolic acid, salts thereof and esters thereof.
(3) The skin external preparation according to (1) or (2), wherein the diester of the dimer acid is dimer linoleic acid di (phytosteryl, isostearyl, cetyl, stearyl, behenyl).
(4) The external preparation for skin according to any one of (1) to (3), further comprising a polyhydric alcohol ester of alginic acid.
(5) The external preparation for skin according to any one of (1) to (4), wherein the polyhydric alcohol ester of alginic acid is a propylene glycol ester of alginic acid.
(6) The external preparation for skin according to any one of (1) to (5), which is in the form of an oil-in-water emulsifier.
(7) The external preparation for skin according to any one of (1) to (6), which is a cosmetic for humans with enhanced transdermal water dispersion loss (TEWL).

  According to the present invention, once enhanced TEWL can rapidly reduce this without forming a vicious circle with respect to the skin.

(1) Ursolic acid or a derivative thereof which is an essential component of the external preparation for skin of the present invention The external preparation for skin of the present invention contains at least one selected from ursolic acid, a salt thereof and an ester thereof as an essential component It is characterized by containing as. The salt of ursolic acid can be used without particular limitation as long as it is an alkali salt that is usually known in cosmetics. For example, alkali metal salts such as sodium salt and potassium salt, alkaline earth such as calcium and magnesium, and the like. Preferred examples include organic amine salts such as metal salts, ammonium salts, triethanolamine salts and triethylamine salts, and basic amino acid salts such as lysine salts and arginine salts. The ursolic acid ester is preferably an aliphatic or aromatic ester having 1 to 30 carbon atoms. For example, as an aliphatic ester, methyl ester, ethyl ester, hexyl ester, 2-ethylhexyl Preferred examples include esters, lauryl esters, stearyl esters, behenyl esters, isostearyl esters, oleyl esters and the like, and aromatic esters include benzyl esters, phenethyl esters, cinnamyl esters, and the like. Such an ester can be produced by reacting an alcohol forming an ester with a halogenating reagent such as thionyl chloride, converting it to a halide, and then condensing with ursolic acid in the presence of an alkali. A production example is shown below.

<Production Example 1>
4.5 g of ursolic acid is dissolved in 100 ml of dimethylformamide, 1 g of potassium carbonate is added thereto, the temperature is raised to 80 ° C., 1 ml of methyl iodide is added dropwise thereto, and the mixture is reacted for 3 hours at 80 ° C. After distillation, the residue was purified by silica gel column chromatography (elution solvent: chloroform) to obtain 2.7 g of ursolic acid methyl ester.

<Production Example 2>
4.5 g of ursolic acid and stearyl chloride obtained by reacting 3 g of stearyl alcohol and 2 ml of thionyl chloride were treated in the same manner as in Production Example 1 to obtain 3.9 g of ursolic acid stearyl ester.

<Production Example 3>
4.5 g of ursolic acid and oleyl chloride obtained by reacting 3 g of oleyl alcohol and 2 ml of thionyl chloride were treated in the same manner as in Production Example 1 to obtain 3.2 g of oleic acid oleyl ester.

<Production Example 4>
4.5 g of ursolic acid and 1.5 ml of benzyl chloride were treated in the same manner as in Production Example 1 to obtain 2.4 g of ursolic acid benzyl ester.

  The skin external preparation of the present invention can contain such ursolic acid, a salt of ursolic acid, and an ester of ursolic acid alone or in combination of two or more. In particular, a preferred form in the external preparation for skin of the present invention is a form containing only ursolic acid benzyl ester. This component works with dimer acid diesters described later on the skin with enhanced TEWL, reconstructs the barrier mechanism in the skin, and eliminates the vicious circle of reduced skin barrier function and enhanced sympathetic nerve. Play. In order to exert such an action, at least one selected from ursolic acid, salts thereof and esters thereof is 0.01 to 5% by mass, more preferably 0.05%, based on the total amount of the external preparation for skin. It is preferable to contain -1 mass%. This is because even if the amount is too large, there are cases where it is difficult to dissolve and mix, and if it is too small, there may be cases where the effect is not achieved.

(2) Dimer acid diester which is an essential component of the skin external preparation of the present invention The skin external preparation of the present invention is characterized by containing a dimer acid diester as an essential component. Dimer acid is an aliphatic dibasic acid having 36 carbon atoms (having a double bond) obtained by dimerizing an unsaturated fatty acid having 18 carbon atoms. The unsaturated fatty acid having 18 carbon atoms is preferably mainly composed of oleic acid and linoleic acid obtained from plants such as soybean, and the structure of dimer acid is dimer oleic acid or dimer linoleic acid. Dimer acid is commercially available as “dimer acid”, and a commercially available product can be used in the present invention. However, a commercially available product is a mixture of a large number of compounds, but has one cyclic structure in the molecular structure. The main component is an aliphatic dibasic acid having 36 carbon atoms. Such dimer acid can be directly converted into a diester, or used in the form of a hydrogenated product obtained by partially or completely inducing unsaturated bonds partially or completely by hydrogenation. You can also. Preferred examples of the alcohol moiety constituting the dimer of dimer acid include higher alcohols usually used in cosmetics, dimer alcohol obtained by reducing dimer acid, and the like. The higher alcohols include cholesterol and aliphatic cyclic alcohols such as phytosterols. As a method for condensing dimer acid and alcohol into a diester, it can be produced by halogenating dimer acid with thionyl chloride or the like and then condensing in the presence of alkali. Among the diesters of such dimer acids, preferred examples include diisostearyl dimerdilinoleate, diisostearyl hydrogenated dimerisolinoleate, diphytosteryl dimerdilinoleate, diphytosteryl hydrogenated dimerlinoleate. Dimerlinoleic acid dimer dilinoleyl, hydrogenated dimer dilinoleic acid dibehenyl, dimer dilinoleic acid dimer dilinoleyl, hydrogenated dimer dilinoleic acid dimer dilinoleyl and the like, and mixed alcohol esters such as die It is also preferable to take a form like dimerginoleate (phytosteryl, isostearyl, cetyl, stearyl, behenyl). There are commercially available diesters of such dimer acids, and such commercially available products can be purchased and used. Examples of such commercially available products include prandour (manufactured by Nippon Seika Co., Ltd .; Plandool-S, Plandool-H), hydrogenated, which is dimer linoleic acid di (phytosteryl, isostearyl, cetyl, stearyl, behenyl). Rasplan PI-DA (LUSPLAN PI-DA; manufactured by Nippon Seika Co., Ltd.) which is isostearyl dimerlinoleate / phytosteryl, Rusplan DD-DA5 (LUSPLAN DD-DA5) which is hydrogenated dimerlinoleic acid dimerlinoleyl; (Nippon Seika Co., Ltd.), hydrogenated dimer dilinoleic acid dimer dilinoleil, Rusplan DD-DA7 (LUSPLANDD-DA7; manufactured by Nippon Seika Co., Ltd.) and the like can be preferably exemplified.

  In the external preparation for skin of the present invention, the dimer acid diester acts together with the ursolic acid, its salt, and its ester to reconstruct the skin barrier function of the skin where TEWL is enhanced, and promptly apply TEWL. It works to make a transition to the steady state. In order to exert such an action, such dimer acid diesters may contain only one species, or may contain two or more species in combination. In order to exert such an action, the dimer acid diester is preferably contained in an amount of 0.1 to 10% by mass, more preferably 0.2 to 1%, based on the total amount of the external preparation for skin. % By mass. This is because if the amount is too small, the above-described effects may not be exhibited, and if the amount is too large, the feeling of use may be lost or the stability of the preparation may be affected.

(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 skin external preparation of the present invention is not particularly limited as long as it is externally administered to the skin, and examples thereof include cosmetics, skin external medicines, and skin external goods. Further, the dosage form may be any combination of solubilization, microemulsion, emulsification system and dispersion system. Particularly preferred are emulsifier type cosmetics, among which oil-in-water emulsifier type cosmetics. This is because the dimer acid contains water and builds a stronger barrier layer on the skin, which makes it easier to break rough skin and a vicious cycle of stimulating factors. In such emulsification, emulsification using a water-soluble polymer is preferable, and examples of the water-soluble polymer include alginic acid, polyhydric alcohol esters of alginic acid, and salts thereof.

  Here, the polyhydric alcohol constituting the polyhydric alcohol ester of alginic acid can be used without particular limitation as long as it is used in an external preparation for skin, and has 2 to 4 carbon atoms. Are preferred, and those having no ether bond are preferred. Specifically, propylene glycol, glycerin, 1,3-butanediol, ethylene glycol and the like can be preferably exemplified, and propylene glycol can be particularly preferably exemplified from the balance between hydrophilicity and lipophilicity. All of these polyhydric alcohol esters of alginic acid are known compounds, and their production methods are already known. As a method for producing such an ester of a polyhydric alcohol of alginic acid, a reaction of a salt of alginic acid such as sodium alginate and the corresponding monohalide of polyhydric alcohol can be exemplified. For example, in the case of a propylene glycol ester of alginic acid, sodium alginate and 1-chloro-2-propanol may be reacted in the presence of potassium carbonate in a hydrous alcohol, or in the case of glyceryl alginate, 1-chloro-propanol in the above reaction can be prepared by treating in the same manner instead of 1-chloro-2,3-propanediol. Some of these esters are already on the market, and such commercial products can be purchased and used. As a suitable commercially available product, for example, as long as it is propylene glycol ester of alginic acid, “Kimiloid LLV”, “Kimiloid LV”, “Kimiloid MV”, “Kimiloy HV”, “Kimiroid BF” sold by Kimika Co., Ltd. "," Kimiloid NLSK "and the like. These differ in viscosity and degree of esterification. Particularly preferred for use as the emulsified composition of the present invention is “Chimiloid NLSK”. In the emulsified composition of the present invention, the polyhydric alcohol ester of alginic acid has an action of stably emulsifying and dispersing the oil component. These esters of polyhydric alcohols of alginic acid can contain only one species or can be contained in combination of two or more. The preferable content of the polyhydric alcohol ester of alginic acid in the external preparation for skin of the present invention is 0.1 to 5% by weight in total with respect to the total amount of external preparation for skin, more preferably 0.8%. 2-2% by weight. Moreover, when the polyhydric alcohol of alginic acid is contained, it is more preferable to contain alginic acid and / or a salt thereof in combination. In such a case, the preferable content of alginic acid and / or a salt thereof is 0.1 to 5% by mass, and more preferably 0.3 to 1% by mass. Such a component can be used by partially constructing a crosslinked structure by adding a salt such as calcium chloride or magnesium chloride if desired. By containing these, the micelles of the emulsion and the solubilized product can be stabilized and allowed to exist on the 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. Such optional ingredients include, for example, macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, hydrogenated coconut oil Oil, wax, oil such as beeswax, canola wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax, liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum , Hydrocarbons such as microcrystalline wax; higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid; cetyl alcohol, stearyl alcohol, isostearyl Higher alcohols such as alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, cetostearyl alcohol; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, malic acid Diisostearyl, di-2-ethylhexanoic acid ethylene glycol, dicaprate neopentyl glycol, di-2-heptylundecanoic acid glycerin, tri-2-ethylhexanoic acid glycerin, tri-2-ethylhexanoic acid trimethylolpropane, tri Synthetic ester oils such as trimethylolpropane isostearate and pentane erythritol tetra-2-ethylhexanoate; dimethylpolysiloxane, methylphenylpoly Linear polysiloxanes such as oxane and diphenylpolysiloxane; cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and dodecamethylcyclohexanesiloxane; amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, Oil agents such as silicone oils such as modified polysiloxanes such as fluorine-modified polysiloxanes; Anionic surfactants such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, triethanolamine ether of alkyl sulfates; Cationic surfactants such as stearyltrimethylammonium, benzalkonium chloride, laurylamine oxide; imidazoline-based amphoteric surfactants (2-cocoyl-2-imida Zolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine surfactants (alkyl betaine, amide betaine, sulfobetaine, etc.), and amphoteric surfactants such as acylmethyltaurine; sorbitan fatty acid esters (sorbitan) Monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (glyceryl monostearate, etc.), propylene glycol fatty acid esters (propylene glycol monostearate, etc.), hardened castor oil derivatives, glycerin alkyl ethers, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbite fatty acid esters (POE-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 alkyl phenyl ethers (POE nonylphenyl) Ethers, etc.), Pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics, POE castor oil / hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), Nonionic surfactants such as sucrose fatty acid ester and alkyl glucoside; polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene Polyhydric alcohols such as recall, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4-hexanediol, 1,2-hexanediol, 1,2-octanediol; sodium pyrrolidonecarboxylate Moisturizing ingredients such as lactic acid and sodium lactate; powders such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, barium sulfate, etc. whose surface may be treated Body, the surface may be treated, inorganic pigments such as bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, zinc oxide; surface may be treated, mica Pearl agents such as titanium, fish phosphorus foil, bismuth oxychloride; red 202 which may be raked, 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; para-aminobenzoic acid UV absorbers; anthranils Acid UV absorbers; salicylic acid UV absorbers; cinnamic acid UV absorbers; benzophenone UV absorbers; sugar UV absorbers; 2- (2′-hydroxy-5′-t-octylphenyl) benzo Ultraviolet absorbers such as triazole 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- Preferred examples include vitamins such as tocopherol, γ-tocopherol, vitamin E acetate and the like, vitamins D, vitamin H, pantothenic acid, panthetin, pyrroloquinoline quinone, and the like; and antibacterial agents such as phenoxyethanol. The skin external preparation can be manufactured by this invention by processing these components in accordance with a conventional method.

  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 these examples.

  According to the formulation shown below, a cosmetic 1 in the form of an oil-in-water emulsifier, which is an external preparation for skin of the present invention, was produced. That is, ingredients (a), (b), and (c) were heated to 80 ° C., and (b) was gradually added to a with stirring. Thereafter, (c) was also added to form a cross-link, and stirring and cooling were performed to obtain Cosmetics 1.

<Test Example 1>
Four parts of 2cm x 4cm were made on the inner side of the forearm of a volunteer paneler (n = 5), and these parts were stripped 10 times with adhesive tape, and then a 2 mass% sodium lauryl sulfate aqueous solution was applied for 24 hours. And a rough skin vicious circle model was created. That is, this model is a model in which rough skin with poor recoverability is created by exposing the skin to irritant stress for a long time by removing the barrier layer of the skin and applying inflammatory stress to the skin. This can be confirmed by the TEWL value after creating rough skin. As described above, TEWL was measured with a tevameter (manufactured by Integral Co., Ltd.), and after confirming that there was no difference between the parts, cosmetic 1 was applied to one part and the plan of cosmetic 1 was applied to one part. The cosmetic of Comparative Example 1 in which Dole H was replaced with water was applied, and the cosmetic of Comparative Example 2 in which ursolic acid benzyl ester of Cosmetic 1 was replaced with water was applied to one site. The remaining 1 site was not treated. After this treatment was continued once a day, TEWL of each part was again measured with a tevameter. The results are shown in Table 1. From this, it can be seen that Cosmetic 1 exhibits an excellent skin barrier function restructuring action due to the synergistic action of Plandol H and ursolic acid benzyl ester.

  In the same manner as in cosmetic 1 of Example 1, cosmetic 2 as an external preparation for skin of the present invention was produced according to the formulation shown in Table 3 below. In the evaluation of the method of Test Example 1, this was changed from TEWL of 35.2 to 19.2 after the test was completed, and the effect of the present invention was confirmed.

  In the same manner as in cosmetic 1 of Example 1, cosmetic 3 as an external preparation for skin of the present invention was produced according to the formulation shown in Table 4 below. In the evaluation of the method of Test Example 1, the TEWL, which was 34.6 at the beginning, changed to 18.5 after the test was completed, and the effect of the present invention was confirmed.

  In the same manner as cosmetic 1 in Example 1, cosmetic 4 as an external preparation for skin of the present invention was produced according to the formulation shown in Table 5 below. In the evaluation of the method of Test Example 1, the TEWL, which was 35.1 at the beginning, changed to 17.5 after the test was completed, and the effect of the present invention was confirmed.

  In the same manner as cosmetic 1 in Example 1, cosmetic 5 as an external preparation for skin of the present invention was produced according to the formulation shown in Table 6 below. In this evaluation, in the evaluation of the method of Test Example 1, TEWL, which was 34.8 at the beginning, changed to 15.9 after the test was completed, and the effect of the present invention was confirmed.

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

Claims (7)

1) One or more types selected from ursolic acid, a salt thereof, and an ester thereof, and 2) a dimer acid diester, an external preparation for skin. The external preparation for skin according to claim 1, comprising at least benzyl ursolate as at least one selected from ursolic acid, salts thereof and esters thereof. The external preparation for skin according to claim 1 or 2, wherein the diester of dimer acid is dimer linoleic acid di (phytosteryl, isostearyl, cetyl, stearyl, behenyl). The skin external preparation according to any one of claims 1 to 3, further comprising a polyhydric alcohol ester of alginic acid. The external preparation for skin according to any one of claims 1 to 4, wherein the polyhydric alcohol ester of alginic acid is a propylene glycol ester of alginic acid. It is an oil-in-water emulsifier form, The skin external preparation in any one of Claims 1-5 characterized by the above-mentioned. The external preparation for skin according to any one of claims 1 to 6, which is a cosmetic for humans having enhanced transdermal water dispersion (TEWL).