JP2014040381A - External skin treatment composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an external skin treatment composition having a branched structure with a sterically-bulky chemical structure; achieving high transdermal absorption in a water soluble compound having skin whitening or rough skin-improvement effect; and having high stability as a formulation and excellent use feeling.SOLUTION: An external skin treatment composition is characterized by containing 1) ursolic acid phosphate and/or a salt thereof and 2) alkylene glycol alginate, where it is more preferable that the alkylene glycol alginate is propylene glycol alginate and isostearic acid and 2-ethylhexyl isononanoate are contained.

Description

The present invention relates to an external composition for skin, and more particularly, to an external composition for skin containing a whitening or roughening component.

Triterpenes are found in plants that are the source of most herbal medicines, such as ginseng plants such as ginseng, fungi such as chorei and sarnococcoli, and have many triterpene skeletons to date Has been isolated and purified. Among these triterpene compounds, triterpenic acids having a carboxyl group have a melanin production inhibitory action, an anti-inflammatory action, and a collagen fiber bundle structure restructuring action (see, for example, Patent Document 1 and Patent Document 2). It is formulated as a useful cosmetic and food ingredient. However, since many compounds having a triterpene skeleton are highly hydrophobic compounds, the solubility in aqueous components is extremely low, and when used as a cosmetic ingredient, there are restrictions on the amount and formulation. There were many. In particular, ursolic acid and ursolic acid derivatives are known to exhibit various biological activities such as wrinkle improving action, skin beautifying action, antioxidant action, melanin production inhibiting action, and anti-inflammatory action. It was difficult to formulate until the above effect was fully exhibited.

For this reason, as a result of derivatization aimed at improving solubility, ursolic acid phosphate ester was found. Ursolic acid phosphate ester is a whitening effect (for example, see Patent Document 3), a rough skin improving effect (for example, see Patent Document 4), and a technique for containing cosmetics at a high concentration (for example, Patent Document 5). Is reported and is very useful. However, the water-solubility is increased by phosphorylation, so that the surface active ability is increased, resulting in problems such as poor emulsification, stability over time, deterioration of high-temperature stability, and feeling of use (particularly stickiness) in emulsion compositions and the like. There was a need for a solution.

On the other hand, as an attempt to achieve a higher whitening or rough skin improvement effect, studies have been made to improve skin permeability or storage (Patent Document 6) by devising prescription ingredients. In addition, it has been reported that skin permeability is controlled by a method using hydroxylated phospholipid or the like (Patent Document 7). However, even in these methods, in the case of a compound having a sterically bulky branched structure and a water-soluble compound, skin permeation is limited or low in effectiveness, and a high whitening or roughening effect is obtained. It was a difficult situation. Therefore, a formulation and a dosage form that can realize high transdermal absorption of these compounds have been demanded.

JP-A-11-005727 Japanese Patent Laid-Open No. H9-143050 International Publication No. WO2006-132033 JP 2007-24464A JP 2007-308385 A JP 2007-332115 A JP 2008-115109 A

Even for compounds that have a three-dimensionally bulky branched structure and are water-soluble and have a whitening or rough skin-improving effect, they can achieve high transdermal absorbability and are highly stable as preparations, and are easy to use. In addition, an object of the present invention was to provide an excellent skin external composition.

In view of such a situation, the present inventors pay attention to emulsifiers, surfactants and oils, which have a great influence on the effects of transdermal absorption and formulation stability, and use these raw materials that can be used in the cosmetics field. As a result of investigation and diligent research aiming at a new composition for external use on the skin, it was found that a new composition for external use on the skin as shown below can solve the problem and completed the present invention. That is, the present invention is as follows.

<1> An external composition for skin comprising 1) ursolic acid phosphate and / or salt thereof, and 2) alginic acid alkylene glycol ester.
<2> The external composition for skin according to <1>, wherein the alginic acid alkylene glycol ester is alginate propylene glycol ester.
<3> The external composition for skin according to <1> or <2>, comprising isostearic acid.
<4> The external composition for skin according to any one of <1> to <3>, comprising 2-ethylhexyl isononanoate.

According to the present invention, even a compound having a three-dimensionally bulky branched structure and water-soluble whitening or rough skin can achieve high transdermal absorbability and is stable as a preparation. It is possible to provide an external composition for skin having high properties and excellent usability.

<Ursoleic acid phosphate ester and / or salt thereof used in the present invention>
Ursolic acid phosphoric acid ester and / or its salt is formed by phosphorylating at least one of the hydroxyl groups of ursolic acid having a hydroxyl group. The ursolic acid having a hydroxyl group can be applied without particular limitation as long as it is used in the field of skin external preparations such as cosmetics. Induction of ursolic acid to a phosphate ester may be performed in accordance with a generally known phosphorylation method. For example, ursolic acid is treated with 1 to 3 equivalents of diethyl-N, N-diethyl phosphoramidate in the presence of tetrazole, reacted with t-butyl hydroperoxide to form methyl phosphate of ursolic acid, It can be produced by reacting bromotrimethylsilane. Ursolic acid phosphate obtained by treating ursolic acid by such a method has the structure shown above (Chemical Formula 1). The ursolic acid phosphate ester thus obtained can be converted into a salt by reacting with an alkali usually used in pharmaceuticals and cosmetics. Examples of such salts include alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium and magnesium, organic amine salts such as ammonium salts, triethanolamine salts, and triethylamine salts, lysine salts, Preferred examples include basic amino acid salts such as arginine salts, and potassium salts are more preferred. The ursolic acid phosphate ester or salt thereof thus obtained becomes highly soluble in an aqueous carrier, and its drug activity is significantly improved compared to the original triterpenic acid. When the ursolic acid phosphate of the present invention is contained in a skin external preparation or the like, the content thereof is 0.001 to 1% by mass, preferably 0.01 to 0.1% by mass, based on the total amount of the skin external preparation. Is appropriate. This is because if the amount is too small, the drug activity may not be expressed, and if the amount is too large, the drug activity may reach its peak.

<Alginic acid alkylene glycol ester used in the present invention>
Alginic acid alkylene glycol esters are also available on the market, and any alginic acid alkylene glycol ester can be used without particular limitation as long as it is used in an external composition for skin. The alkylene glycol of the alginic acid alkylene glycol ester preferably has 2 to 4 carbon atoms. Specifically, ethylene glycol, propylene glycol, 1,3-butanediol and the like can be preferably exemplified, and propylene glycol can be particularly preferably exemplified from the balance between hydrophilicity and lipophilicity. These alginic acid alkylene glycol esters are all known compounds, and their production methods are already known. As a method for producing such an alginic acid alkylene glycol ester, a salt of alginic acid such as sodium alginate and a corresponding monohalide of alkylene glycol can be reacted in the presence of an alkali. For example, a propylene glycol alginate can be produced by reacting sodium alginate and 1-chloro-2-propanol in a hydrous alcohol in the presence of potassium carbonate or the like. In the composition for external use of the skin of the present invention, one kind of alginic acid alkylene glycol ester may be contained alone, or two or more kinds may be contained in combination. The total amount of the skin external composition is preferably 0.01 to 3% by mass, more preferably 0.1 to 2% by mass.

<Isostearic acid used in the present invention>
Some isostearic acids are already on the market, and any isostearic acid can be used without particular limitation as long as it is used in a composition for external use on the skin. In the external composition for skin of the present invention, isostearic acid is preferably contained in an amount of 0.01 to 3% by mass, more preferably 0.1 to 1% by mass.

<2-ethylhexyl isononanoate used in the present invention>
There are some commercially available products of 2-ethylhexyl isononanoate, and any of them can be used without particular limitation as long as it is used in a composition for external use on the skin. In the composition for external use of the skin of the present invention, 2-ethylhexyl isononanoate is preferably contained in an amount of 1 to 20% by mass, more preferably 5 to 15% by mass.

The external composition for skin referred to in the present invention is not particularly limited as long as it is externally administered to the skin. For example, cosmetics including quasi-drugs, skin external goods and the like can be suitably exemplified. Of these, cosmetics are particularly preferred. In addition, the external composition for skin of the present invention can take any of the conventionally known emulsion dosage forms, essence dosage forms, cream dosage forms, and powder-containing dosage forms. As the cosmetic, any of basic cosmetics, hair cosmetics, and makeup cosmetics can be applied, but it is particularly preferable to apply to basic cosmetics.

In the composition for external use of the skin of the present invention, in addition to the above-mentioned components, optional components usually used in cosmetics and external preparations for skin can be contained. Examples of such optional ingredients include macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, and hardened coconut oil. Oil, wax, liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum, oil, wax, liquid wax, liquid paraffin, squalane, bean wax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin , Hydrocarbons such as microcrystalline wax, higher fatty acids such as oleic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid, cetyl alcohol, stearyl alcohol, isostearyl alcohol, Higher alcohols such as alcohol, octyldodecanol, myristyl alcohol, cetostearyl alcohol, cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, diacid malate Isostearyl, ethylene glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, glycerin tri-2-ethylhexanoate, tri-2-ethylhexanoate trimethylolpropane, triisostearin Synthetic ester oils such as acid trimethylolpropane, tetra-2-ethylhexanoic acid pentane erythritol, dimethylpolysiloxane, methylphenylpolysiloxane, diphenyl Linear polysiloxanes such as polypolysiloxane, cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexanesiloxane, amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, fluorine-modified Oil agents such as silicone oils such as modified polysiloxanes such as polysiloxane, fatty acid soap (sodium laurate, sodium palmitate, etc.), anionic surfactants such as potassium lauryl sulfate, alkyl sulfate triethanolamine ether, stearyl trimethyl chloride Cationic surfactants such as ammonium, benzalkonium chloride, laurylamine oxide, betaine surfactants (alkyl betaines, amide betaines, sulfobetaines, etc.) ), Imidazoline-based amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), amphoteric surfactants such as acylmethyltaurine, sorbitan fatty acid esters (sorbitan monoester) Stearate, sorbitan sesquioleate, etc.)
Glycerin fatty acids (such as glyceryl monostearate), propylene glycol fatty acid esters (such as propylene glycol monostearate), hydrogenated castor oil derivatives, glycerin alkyl ethers, POE sorbitan fatty acid esters (POE sorbitan monooleate, monostearic acid) Polyoxyethylene sorbitan, etc.), POE sorbite fatty acid esters (POE-sorbite monolaurate, etc.), POE glycerin fatty acid esters (POE-glycerin 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.), Te Tronics, POE castor oil / hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), nonionic surfactants such as sucrose fatty acid ester, alkyl glucoside, polyethylene glycol, glycerin, 1,3-butylene glycol Erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4-hexylene glycol, 1,2-he Polyhydric alcohols such as sundiol, 1,2-octanediol, moisturizing ingredients such as sodium pyrrolidonecarboxylate, lactic acid, sodium lactate, guar gum, quince seed, carrageenan, galactan, gum arabic, pectin, mannan, starch, xanthan gum , Curdlan, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, methylhydroxypropylcellulose, chondroitin sulfate, dermatan sulfate, glycogen, heparan sulfate, hyaluronic acid, sodium hyaluronate, tragacanth gum, keratan sulfate, chondroitin, mucoitin sulfate, hydroxyethyl guar gum, carboxy Methyl guar gum, dextran, keratosulfate, locust bean gum, succinoglucan, caronic acid, chitin, Thickeners such as tosan, carboxymethyl chitin, agar, polyvinyl alcohol, polyvinyl pyrrolidone, carboxy vinyl polymer, alkyl-modified carboxy vinyl polymer, sodium polyacrylate, polyethylene glycol, bentonite, surface may be treated, mica, Powders such as talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, silicic anhydride (silica), aluminum oxide, barium sulfate, surface may be treated, bengara, yellow iron oxide, black iron oxide, Cobalt oxide, ultramarine, bitumen, titanium oxide, zinc oxide inorganic pigments, surface may be treated, pearlescent agents such as titanium mica, fish phosphorus foil, bismuth oxychloride, red may be raked 202, Red 228, Red 226, Yellow 4, Blue 40 No. 4, Yellow No. 5, Red No. 505, Red No. 230, Red No. 223, Orange No. 201, Red No. 213, Yellow No. 204, Yellow No. 203, Blue No. 1, Green No. 201, Purple No. 201, Red No. 204 Organic dyes such as polyethylene powder, polymethyl methacrylate, nylon powder, organic powders such as organopolysiloxane elastomers, paraaminobenzoic acid UV absorbers, anthranilic acid UV absorbers, salicylic acid UV absorbers, cinnamon Acid UV absorber, benzophenone UV absorber, sugar UV absorber, 2- (2′-hydroxy-5′-t-octylphenyl) benzotriazole, 4-methoxy-4′-t-butyldibenzoylmethane ultraviolet absorbing agents and the like, ethanol, lower alcohols such as isopropanol, vitamin a or a derivative thereof, vitamin B Hydrochloride, vitamin _{B 6} tripalmitate, vitamin _{B 6} dioctanoate, vitamin _{B 2} or derivatives thereof, vitamin _{B 12,} vitamin B such as vitamin _{B 15} or a derivative thereof, alpha-tocopherol, beta-tocopherol, .gamma.-tocopherol, Preferable examples include vitamin E such as vitamin E acetate, vitamin D, vitamin H, pantothenic acid, panthetin, pyrroloquinoline quinone and the like.

<Production Example of Composition for External Use of Skin of the Present Invention>
The composition for external use of the skin of the present invention was prepared according to the formulation shown below. That is, after (A) of Example 1 in Table 1 was heated and dissolved at 60 ° C., the mixture was stirred and mixed at 5000 rpm for 5 minutes in an emulsifier while adding (B) to (A), and the aqueous phase 1 was prepared. Then, (C) was heated and dissolved at 80 ° C., and then gradually added to the aqueous phase 1 and stirred and mixed at 3000 rpm for 10 minutes in an emulsifier. Thereafter, the stirring and mixing in the emulsifier was reduced to 1000 rpm and cooled to 30 ° C., whereby the composition for external use in skin of Example 1 was obtained.

<External skin composition of the present invention>
Example 2 was prepared by substituting ursolic acid phosphoric acid ester with ursolic acid phosphoric acid potassium salt for Example 1. Further, compared to Examples 1 and 2, Examples 3 and 4 in which propylene glycol alginate was substituted with ethylene glycol ester having similar chemical structure, Examples 5 and 6 in which propylene glycol alginate was increased, and Comparative Examples 1 and 2 Comparative Examples 3 and 4 (increase with potassium hydroxide as neutralizing agent) in which propylene glycol alginate was substituted with alkyl-modified carboxyvinyl polymer as another polymer emulsifier, sorbitan as propylene glycol alginate with nonionic surfactant Comparative Examples 5 and 6 substituted with stearic acid ester and POE sorbitan stearic acid ester were also prepared. Further, compared to Examples 1 and 2, Comparative Examples 7 and 8 in which isostearic acid was omitted, Examples 7 and 8 and Comparative Examples 9 and 10 in which the amount of isostearic acid was increased, and Comparative Examples 11 and 12 in which isostearic acid was replaced with stearic acid. In Examples 9 and 10 in which 2-ethylhexyl isononanoate was increased, Comparative Examples 13 and 14 in which 2-ethylhexyl isononanoate was substituted with glycerin tri-2-ethylhexanoate as a polar oil, and cetyl isooctanoate as a polar oil were used. Comparative Examples 15 and 16 and Comparative Examples 17 and 18 in which isostearic acid and 2-ethylhexyl isononanoate were omitted were similarly prepared. It shows in Tables 1-3.

<Test Example 1 Evaluation of transdermal absorbability of external composition for skin>
Six panels of 1 cm × 1 cm were provided on the inner part of the forearm of 10 panelists, and 7 μL of the test sample, which was the above-prepared skin external composition, was applied to each panel and allowed to stand at 20 ° C. for 1 hour, followed by tetrahydrofuran (THF) The skin was wiped off with a cotton wool impregnated with 100% of this cotton, and this cotton wool was extracted three times with 100 ml of THF, and the recovered amount of ursolic acid phosphate ester or ursolic acid phosphate potassium salt in the extract was quantified by high performance liquid chromatography. . The recovery rate was defined as transdermal absorbability (the lower the value, the higher the transdermal absorbability). Each test sample was evaluated twice, and the averages are shown in Tables 1-3.

<Test Example 2 Appearance, color and odor evaluation of composition for external use on skin>
After preparing the test sample, it was stored at 50 ° C. One week after the preparation, appearance, color and odor were evaluated. However, on the day before the evaluation, the test sample stored at 50 ° C. was stored at 20 ° C. for 24 hours and evaluated. In terms of appearance, the absolute evaluation was evaluated by comparing the color and odor with those separately stored at 5 ° C. The criteria for each evaluation are shown below. The results are shown in Tables 1-3.

[Appearance evaluation]
0: Emulsified neatly.
1: Although emulsified, the emulsified particles are enlarged and the transparency is enhanced.
2: Emulsification failure is observed (less than 5% of the total).
3: Emulsification is broken and oil is separated.

[Color and smell evaluation]
0: Same as stored at 5 ° C.
1: A slight difference is seen compared with a 5 degreeC storage goods. It is a level that cannot be understood unless it is compared with products stored at 5 ° C.
2: A difference is seen compared with a 5 degreeC storage goods. Even if it is not compared with a product stored at 5 ° C., it can be easily understood.
3: Discoloration or odor change is remarkable. It is not suitable as a composition for external use on the skin.

<Test Example 3 Skin feel evaluation of composition for external use>
A questionnaire was conducted regarding the feeling of use of the composition for external use on the skin. The evaluation criteria are shown below. In addition, Tables 1 to 3 show the most frequent results for five people.
A: There is no stickiness and it is a very good feeling.
B: Although it feels a little sticky, it is a relatively good feeling.
C: A feeling of stickiness is felt and the feeling of use is bad.
D: A feeling of stickiness is considerably felt, and it is a very bad feeling of use. It is not suitable as a composition for external use on the skin.

From the results of Tables 1 to 3, according to the present invention, even in a compound having a three-dimensionally bulky branched structure having an effect of improving skin whitening or roughening the skin and having a high solubility, it is highly transdermal. It can be seen that a composition for external use on skin that can be absorbed, has high stability as a preparation, and has an excellent usability.

The present invention relates to an external preparation for skin, and more specifically, can be applied to an external preparation for skin containing a whitening or rough skin improving component.

Claims (4)

An external composition for skin comprising 1) ursolic acid phosphate and / or a salt thereof, and 2) an alginic acid alkylene glycol ester.
The composition for external use on skin according to claim 1, wherein the alginic acid alkylene glycol ester is alginate propylene glycol ester. The composition for external use according to claim 1 or 2, comprising isostearic acid. The external composition for skin according to any one of claims 1 to 3, comprising 2-ethylhexyl isononanoate.