JP2015134741A - External preparation for skin, and cosmetic composition and quasi drug composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an external preparation for skin whose active ingredient smoothly penetrates the horny layer and epidermis in the skin, and which exhibits an excellent percutaneous absorption ability.SOLUTION: An external preparation for skin is characterized by containing two or more kinds of surfactant which forms a hydrophobic aggregate under the moisture content environment of at least one with a moisture content of 15% or more and 40% or less, and forms a hydrophilic aggregate under the moisture content environment of at least one with a moisture content of 65% or more and 75% or less.

Description

  The present invention relates to an external preparation for skin with improved transdermal absorbability. The present invention also relates to a composition for providing an external preparation for skin with improved transdermal absorbability.

  The skin is an important tissue that defines the living body and the outside world. When the skin is damaged, it means that the protective wall of the living body is broken, which may cause serious damage to the living body. In that sense, it is necessary to quickly remove the z-damage in the skin. However, in order for a drug for removing the damage to reach the skin, the protective wall function of the skin becomes an obstacle. For this reason, various means for promoting percutaneous absorption have been developed.

  For example, a method using a card house or network structure constructed by an oily gel (Patent Document 1), a method using ultrasonic waves as a driving force for percutaneous absorption (Patent Document 2), N-methyl-2-pyrrolidone, etc. A method using a solvent (Patent Document 3), a method using a transdermal absorption promoting component such as lauroyl sarcosine (Patent Document 4), a liposome having an inner aqueous phase inside a sphere having a phospholipid bilayer structure, Examples thereof include a method in which a drug is encapsulated in an internal aqueous phase of niosome and blended in a skin external preparation (Patent Document 5, Patent Document 6).

  Other technologies that use bicontinuous cubic liquid crystals to enable the inclusion of silicone oils and polar oils (Patent Document 7) and application techniques for oil-based cleansing using a microemulsion phase (Patent Document 8) are known. It has been.

JP 2000-103722 A JP 11-335271 A JP-A-10-265379 Japanese Patent Application Laid-Open No. 09-169637 JP 2004-143080 A International Publication No. 2008/149601 Pamphlet JP 2005-132797 A JP 2005-194249 A

  This invention makes it a subject to provide the new skin external preparation with improved transdermal absorbability.

  The inventors of the present invention have advanced research in order to solve the above-described problems, and have focused on the layer configuration constituting the skin. Human skin is composed of the stratum corneum, epidermis, and dermis in this order from the outside, and the stratum corneum is an environment with low water content and high hydrophobicity, while the epidermis is an environment with high water content and high hydrophilicity. is there. Therefore, in the conventionally proposed technique, it is considered that the active ingredient is not sufficiently penetrated in either the stratum corneum or the epidermis.

Based on the above findings, the present inventors have come up with the idea that the above problem can be solved if there is a structure whose structure can change from hydrophobic to hydrophilic depending on the moisture environment. As a result of further intensive studies in consideration of the idea and the moisture environment of the skin, among a plurality of types of surfactant composites, at least one moisture content environment of a moisture content of 15% or more and 40% or less A complex that forms a hydrophobic aggregate underneath and that forms a hydrophilic aggregate under a moisture content environment of at least one of the moisture content of 65% or more and 75% or less smoothes the stratum corneum and epidermis in the skin The present invention was completed by discovering that a skin external preparation containing the complex has excellent transdermal absorption ability.

The first embodiment of the present invention is a skin external preparation containing a plurality of types of surfactants,
The plurality of types of surfactants form a hydrophobic aggregate in a moisture content environment of at least one of a moisture content of 15% or more and 40% or less, and at least one of a moisture content of 65% or more and 75% or less. An external preparation for skin characterized by forming a hydrophilic aggregate in a point moisture content environment.

The hydrophobic aggregate formed by the plurality of types of surfactants is preferably a cubic liquid crystal phase, and the hydrophilic aggregate formed by the plurality of types of surfactants is preferably a D phase.
The plurality of types of surfactants are 1) one or more selected from the group consisting of α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine and salts thereof, and 2 1) One or more selected from the group consisting of glycerin fatty acid ester, polyglycerin fatty acid ester and pyroglutamic acid glycerin fatty acid ester.

Moreover, it is preferable that the plurality of types of surfactants can further form micelles.
Moreover, it is preferable that the ratio of 1) component and 2) component of said multiple types of surfactant is 3: 4-6: 1.

  On the other hand, in the process of completing the above invention, the present inventors show that the surfactant complex that can form a hydrophobic aggregate and a hydrophilic aggregate depending on the water environment is very unstable. I also found. And the technique which can preserve | save the complex of the said surfactant stably was also discovered.

The second embodiment of the present invention is:
A cosmetic composition or a quasi-pharmaceutical composition comprising a plurality of types of surfactants and a polyhydric alcohol, wherein the plurality of types of surfactants are at least one of a moisture content of 15% or more and 40% or less. A hydrophobic aggregate is formed under a water content environment of at least one, and a hydrophilic aggregate is formed under a water content environment of at least one point out of a water content of 65% to 75%. It is a composition or a quasi-drug composition.

According to the first embodiment of the present invention, an external preparation for skin having improved transdermal absorbability can be provided. In particular, when an external preparation for skin is applied to the skin, it penetrates in the order of the stratum corneum and the epidermis. Therefore, the complex containing the surfactant is hydrophobic in an environment such as the stratum corneum with a low water content. By forming an aggregate having a high hydrophilicity and an aggregate having a high hydrophilicity in an environment such as the epidermis having a high water content, a skin external preparation with a significantly improved transdermal absorbability of the active ingredient is obtained.
In addition, according to the second embodiment of the present invention, a cosmetic composition or a quasi-drug composition in which the storage stability of the complex is improved can be provided.

1 is a diagram showing a three-component phase diagram of three components of 1) bis (γ-N-lauroylglutamyl) lysine sodium salt, 2) glyceryl monooleate, and water in an embodiment of the present invention. It is a graph which shows the result of the permeability evaluation of the whole surface layer in a permeability test.

The first embodiment of the present invention is an external preparation for skin with improved transdermal absorbability, and contains a plurality of types of surfactants. The plural types of surfactants are characterized in that their forms are changed in the existing water environment.
More specifically, the plurality of types of surfactants form a hydrophobic aggregate in a moisture environment of at least one of a moisture content of 15% or more and 40% or less, and a moisture content of 65% or more and 75%. %, The hydrophilic aggregate is formed under a water content environment of at least one point.

  Human skin is composed of the stratum corneum, epidermis, and dermis in this order from the outside, and the stratum corneum has a low water content and high hydrophobicity, while the epidermis has a high water content and high hydrophilicity. It has become. Therefore, in the conventionally proposed technique, it is considered that the active ingredient is not sufficiently permeated in either the stratum corneum or the epidermis. In view of this, the present inventors have formulated a material that forms a hydrophobic aggregate in the stratum corneum, which is a highly hydrophobic environment, and forms a hydrophilic aggregate in the epidermis, which is a highly hydrophilic environment, in the cosmetic. It was conceived that the percutaneous absorbability of the active ingredient was improved by blending together. And it discovered that the material which forms a hydrophobic aggregate in such a highly hydrophobic environment and forms a hydrophilic aggregate in a highly hydrophilic environment can be formed by a specific plurality of surfactants. .

  In the first embodiment of the present invention, a plurality of types of surfactants are used. In the present embodiment, the plurality of types of surfactants form a complex, and the complex forms a hydrophobic aggregate in a moisture environment of at least one of a moisture content of 15% or more and 40% or less, In addition, a hydrophilic aggregate is formed in a moisture content environment of at least one point of a moisture content of 65% or more and 75% or less.

Since the composite forms a hydrophobic aggregate in a moisture content environment of at least one of a moisture content of 15% or more and 40% or less, it forms a hydrophobic assembly in the stratum corneum having a similar moisture content environment. The active ingredient taken into the hydrophobic aggregate is absorbed through the skin together with the hydrophobic aggregate. The upper limit is preferably 35% or less, and more preferably 30% or less.
On the other hand, since the composite forms a hydrophilic aggregate in a moisture environment of at least one point in a moisture content of 65% or more and 75% or less, the hydrophilic assembly is in a skin having a similar moisture content environment. And the active ingredient taken into the hydrophilic assembly is percutaneously absorbed together with the hydrophilic assembly. The upper limit is preferably 73% or less, and more preferably 70% or less.
The external preparation for skin in the first embodiment of the present invention has excellent transdermal absorbability for such reasons.

  The plurality of surfactants in the first embodiment of the present invention change their form depending on the water content environment. Specifically, at least 1) an amphiphile that easily forms a hexagonal liquid crystal phase in the aqueous phase. And 2) an amphiphilic substance that easily forms a lamellar liquid crystal phase in the aqueous phase. The present inventors have found that the composite of the above 1) and 2) components changes its composition into a hydrophobic aggregate and a hydrophilic aggregate depending on the moisture content environment.

1) As an amphiphilic substance that easily forms a hexagonal liquid crystal phase in an aqueous phase, α, ε-bis (γ-N- (10 to 30 carbon atoms) acylglutamyl) lysine and salts thereof are preferable. More preferable specific examples include α, ε-bis (γ-N-lauroylglutamyl) lysine sodium salt (“Perisea L-30” manufactured by Asahi Kasei Chemicals).
The acyl group having 10 to 30 carbon atoms may be a straight chain or a branched structure. Specifically, a decanoyl group, a lauroyl group, a myristoyl group, a palmitoyl group, a stearoyl group, a behenoyl group, Examples include isostearoyl group, oleoyl group, linoloyl group and the like. The number of carbon atoms is more preferably 10-18.
Examples of the salt include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, and the like.

2) Examples of amphiphilic substances that easily form a lamellar liquid crystal phase in the aqueous phase include glycerin surfactants and phospholipids.
Examples of the glycerin surfactant include glycerin fatty acid ester, polyglycerin fatty acid ester, pyroglutamic acid glycerin fatty acid ester, and the like.
Examples of the glyceryl fatty acid ester include glyceryl oleate, glyceryl stearate, glyceryl isostearate, glyceryl palmitate, glyceryl myristate, and glyceryl laurate.
Examples of polyglycerin fatty acid esters include diglyceryl oleate, triglyceryl oleate, tetraglyceryl oleate, polyglyceryl oleate-5, polyglyceryl oleate, tetraglyceryl dioleate, hexaglyceryl tetraoleate, diglyceryl stearate, Examples include triglyceryl stearate, diglyceryl isostearate, triglyceryl isostearate, diglyceryl palmitate, triglyceryl palmitate, diglyceryl myristate, triglyceryl myristate, diglyceryl laurate, and triglyceryl laurate.
Examples of pyroglutamic acid glycerin fatty acid ester include pyroglutamic acid glyceryl oleate, pyroglutamic acid glyceryl stearate, pyroglutamic acid isostearic acid glyceryl pyroglutamate palmitate glyceryl pyroglutamate myristate pyrophosphate, glyceryl pyroglutamate laurate.
Examples of phospholipids include lecithin, hydrogenated lecithin, hydroxylated lecithin, lysolecithin, phosphatidylcholine, phosphatidylethanolamine, and the like.

In the embodiment of the present invention, the components 1) and 2) are usually contained in a total amount of 0.001% by mass or more, preferably 0.01% by mass or more, in the skin external preparation. More preferably, it is contained by mass% or more. On the other hand, it is usually 5% by mass or less, preferably 3% by mass or less, and more preferably 1% by mass or less.
In addition, the content ratio (mass ratio) of the above 1) and 2) components is such that the ratio of the above 1) component and 2) component is usually from 1: 2 to 6: 1, and from 2: 3 to 5: 1. It is preferable that the ratio is 3: 4 to 4: 1, more preferably 1: 1 to 3: 1.

In an embodiment of the present invention, the hydrophobic aggregate formed by the components 1) and 2) is usually a cubic liquid crystal phase, and the hydrophilic aggregate is usually a D phase.
3 components including water when 1) α, ε-bis (γ-N-lauroylglutamyl) lysine sodium salt (Perisea) and 2) glyceryl monooleate are preferred embodiments of the present invention A three-component phase diagram is shown in FIG.
In an embodiment of the present invention, the complex formed by 1) α, ε-bis (γ-N-lauroylglutamyl) lysine sodium salt (Perisea), 2) glyceryl monooleate is within the range of the dotted line shown in FIG. , The form is changed to a hydrophobic aggregate or a hydrophilic aggregate depending on the amount of water.
Further, in this embodiment, as shown in FIG. 1, micelles are formed in a moisture amount environment of at least one point out of a moisture amount of about 75% or more. Specifically, it is preferable to form micelles in a moisture content environment of at least one point of a moisture content of 75% to 80%. Micelles are also highly hydrophilic aggregates, which are preferable because the percutaneous absorption of the active ingredient is good even in an environment where the amount of water is much higher.

  In this embodiment, the formation of the cubic liquid crystal phase, the D phase and the micelle can be confirmed by, for example, observation with a polarizing microscope and X-ray diffraction data.

The external preparation for skin according to the embodiment of the present invention usually contains an active ingredient. The composite formed by the above components 1) and 2) can be percutaneously absorbed in the stratum corneum and epidermis in a state of containing the active ingredient.
Examples of these active ingredients include whitening ingredients, anti-inflammatory ingredients, plant extracts and the like.

The whitening component is not particularly limited as long as it is generally used for pharmaceuticals, cosmetics and the like. For example, 4-n-butylresorcinol, ascorbic acid glucoside, 3-O-ethylascorbic acid, tranexamic acid, arbutin, 2-[(triphenylmethyl) oxy] ethanol, 1- (triphenylmethyl) piperidine, N -(P-Toluyl) cysteic acid, N- (p-methoxybenzoyl) cysteic acid and the like. Some of these whitening components are already on the market, or they can be obtained by synthesis. For example, 3-O-ethylascorbic acid can be synthesized by a known method described in JP-A-8-134055. There are also commercially available products (“VC ethyl” manufactured by Nippon Seika Co., Ltd.), and these can be obtained and used. 2-[(Triphenylmethyl) oxy] ethanol and 1- (triphenylmethyl) piperidine are disclosed in Patent Document WO 2010-074052 as N- (p-toluyl) cysteic acid and N- (p-methoxybenzoyl). Cysteinic acid can be synthesized according to the disclosure since its synthesis method is disclosed in WO2010-058730.
Content of the whitening component in a skin external preparation is 0.01-30 mass% normally, 0.1-10 mass% is preferable and 1-5 mass% is more preferable.

The plant extract is not particularly limited as long as it is generally used for pharmaceuticals, cosmetics and the like. For example, akebi extract, asunaro extract, asparagus extract, avocado extract, achacha extract, almond extract, arnica extract, aloe extract, apricot extract, ginkgo biloba extract, fennel extract, ages extract, enmiso extract, oxon extract, agar extract, auren Extract, ginseng extract, hypericum extract, nettle extract, orange extract, oyster extract, cuckoo extract, chamomile extract, carrot extract, kawara mugi extract, licorice extract, kiwi extract, cucumber extract, guava extract, cucumber extract, gardenia extract, kumazasa extract, clara Extract, walnut extract, grapefruit extract, black rice extract, chlorella extract, mulberry extract, ghetto extract, gentian Kiss, Genno pepper extract, Black tea extract, Burdock extract, Rice extract, Rice fermented extract, Rice bran fermented extract, Rice germ oil, Cowberry extract, Salvia extract, Soap extract, Sasa extract, Hawthorn extract, Sansha extract, Salamander extract, Shiitake extract, Giant extract, lion extract, perilla extract, linden extract, citrus extract, peony extract, ginger cucumber extract, ginger root extract, birch extract, cedar extract, stevia extract, stevia fermented product, crocodile extract, hawthorn essence, elderberry extract, yarrow Extract, mint extract, sage extract, mallow extract, nematode extract, assembly extract, Sorakuhi extract, Daiou extract, soybean extract , Tiso extract, thyme extract, dandelion extract, tea extract, clove extract, chimpi extract, bonito tea extract, pepper extract, touki extract, citrus extract, tonin extract, spruce extract, dokudami extract, tomato extract, natto extract, carrot extract, garlic Extract, Novara extract, Hibiscus extract, Bakumondo extract, Lotus extract, Parsley extract, Birch extract, Hamamelis extract, Butterberry extract, Cypress extract, Biwa extract, Buffalo dandelion extract, Buffalo extract, Bukcho extract, Butcher bloom extract, Grape extract, Grape seed extract , Loofah extract, safflower extract, peppermint extract, bodaiju extract, button extract, hop extract, pine extract, maroonnier extract, mizubasho Extract, Mukuroji Extract, Melissa Extract, Mozuku Extract, Peach Extract, Cornflower Extract, Eucalyptus Extract, Yukinoshita Extract, Yuzu Extract, Lily Extract, Yokuinin Extract, Artemisia Extract, Lavender Extract, Green Tea Extract, Apple Extract, Rooibos Tea Extract, Ganoderma Extract, Lettuce Extract , Lemon extract, forsythia extract, forsythia extract, rose extract, rosemary extract, roman chamomile extract, royal jelly extract, bitumen extract and the like.
Content of the plant extract in a skin external preparation is 0.01-30 mass% normally, 0.1-10 mass% is preferable, and 1-5 mass% is more preferable.

Examples of the anti-inflammatory component include clarinone, grabridine, glycyrrhizic acid, glycyrrhetinic acid, and the like, and preferred are glycyrrhizic acid and its salt, glycyrrhetinic acid alkyl and its salt, and glycyrrhetic acid and its salt.
Content of the anti-inflammatory component in a skin external preparation is 0.01-30 mass% normally, 0.1-10 mass% is preferable and 1-5 mass% is more preferable.

In the external composition for skin according to this embodiment, in addition to the above-mentioned components, components that are usually used in cosmetics and external pharmaceuticals for skin can be contained. Examples of such optional components include hydrocarbons such as liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum, microcrystalline wax, oleic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behen. Acids, higher fatty acids such as undecylenic acid, cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, higher alcohols such as cetostearyl alcohol, dimethylpolysiloxane, methylphenylpolysiloxane, diphenylpolysiloxane Cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexanesiloxane, etc. Siloxane, amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxanes, oils such silicone oils of modified polysiloxanes and fluorine-modified polysiloxanes,
Fatty acid soap (sodium laurate, sodium palmitate, etc.), anionic surfactants such as potassium lauryl sulfate, alkylsulfuric triethanolamine ether, cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide , Betaine surfactants (alkyl betaines, amide betaines, sulfobetaines, etc.), imidazoline amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), acyls Amphoteric surfactants such as methyl taurine, sorbitan fatty acid esters (sorbitan monostearate, sorbitan sesquioleate, etc.), propylene glycol fatty acid esters (propylene glycol monostearate) Etc.), 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-sorbite monolaurate, etc.), POE Glycerin fatty acid esters (POE-glycerol monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE2-octyldodecyl ether, etc.), POE alkyl phenyl ethers (POE) Nonylphenyl ether, etc.), Pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics, POE Machine oil, hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), sucrose fatty acid esters, nonionic surfactants such as alkyl glucosides,
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 Polyhydric alcohols such as 1,2-hexanediol and 1,2-octanediol,
Moisturizing ingredients such as sodium pyrrolidonecarboxylate, lactic acid, sodium lactate,
Gua gum, quince seed, carrageenan, galactan, arabic gum, pectin, mannan, starch, xanthan gum, curdlan, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, methylhydroxypropylcellulose, chondroitin sulfate, dermatan sulfate, glycogen, heparan sulfate, hyaluronic acid, Sodium hyaluronate, gum tragacanth, keratan sulfate, chondroitin, mucoitin sulfate, hydroxyethyl guar gum, carboxymethyl guar gum, dextran, kerato sulfate, locust bean gum, succinoglucan, carolinic acid, chitin, chitosan, carboxymethyl chitin, agar, polyvinyl alcohol , Polyvinylpyrrolidone, carboxyvinyl polymer, alkyl-modified carboxy Vinyl polymers, sodium polyacrylate, polyethylene glycol, a thickener such as bentonite,
The surface may be treated, powders such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, barium sulfate, etc. may be treated. , Bengala, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, zinc oxide inorganic pigments, pearls such as titanium mica, fish phosphorus foil, bismuth oxychloride, etc. whose surface may be treated Agents, which may be raked Red 202, Red 228, Red 226, Yellow 4, Blue 404, Yellow 5, Red 505, Red 230, Red 223, Orange 201, Organic dyes such as red 213, yellow 204, yellow 203, blue 1, green 201, purple 201, red 204, polyethylene powder, polymethyl methacrylate, Nylon powder, organic powders such as organopolysiloxane elastomers,
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 ' UV absorbers such as -t-octylphenyl) benzotriazole, 4-methoxy-4'-t-butyldibenzoylmethane,
Lower alcohols such as ethanol and isopropanol,
Vitamin A or derivatives thereof, vitamin B ₆ hydrochloride, vitamin B ₆ tripalmitate, vitamin B ₆ dioctanoate, vitamin B ₂ or derivatives thereof, vitamin Bs such as vitamin B ₁₂ , vitamin B ₁₅ 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 and the like can be preferably exemplified.

<External preparation for skin>
In the external preparation for skin according to this embodiment, the complex formed by the above components 1) and 2) changes its form depending on the moisture environment, and improves the percutaneous absorption of the active ingredient. Therefore, it is preferable to use as a pharmaceutical, a quasi-drug, a cosmetic, and a skin external miscellaneous product, and a cosmetic is particularly preferable.

  The skin external preparation according to this embodiment can take any of the conventionally known emulsion dosage forms, essence dosage forms, cream dosage forms, and powder-containing dosage forms.

  The skin external preparation in this embodiment is not particularly limited in its production method as long as it can form a complex with the components 1) and 2) above. When a person skilled in the art prepares the skin external preparation according to this embodiment, There is no difficulty.

The second embodiment of the present invention relates to a cosmetic composition or quasi-drug composition in which the storage stability of the complex comprising the components 1) and 2) is improved. The present inventors have found that the complex comprising the components 1) and 2) exhibits excellent storage stability in a polyhydric alcohol.
As the polyhydric alcohol, those used in cosmetics and quasi drugs can be used, such as polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, Examples include dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4-hexylene glycol, 1,2-hexanediol, 1,2-octanediol and the like.
In the second embodiment of the present invention, the content of the polyhydric alcohol in the cosmetic composition or quasi-pharmaceutical composition is preferably 50% by mass or more, and more preferably 70% by mass or more.

EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, the scope of the present invention is not limited only to a specific Example.
<Experimental Examples 1-6, Comparative Experimental Example>
Each component was mixed in the ratio (mass%) shown in Table 1, and the composition which concerns on each experiment example was obtained. The state of the two types of amphiphiles in each composition was determined by observing the obtained composition with a polarizing microscope and confirming X-ray diffraction data. The results are also shown in Table 1. From this result, it can be seen that a composite formed by a combination of specific surfactants forms a cubic liquid crystal phase under a water content of 20% by mass and a D phase under a water content of 70% by mass.

<Test Example 1 Transdermal absorbability evaluation A of composition>
Centaureidine was blended as an active ingredient in the compositions according to Experimental Examples 1 to 7 and Comparative Experimental Example. Specifically, the composition according to Experimental Examples 1A to 7A and Comparative Experimental Example A was obtained by changing to 10% by mass of water and adding 10% by mass of a 0.01% aqueous solution of centauridine.
Evaluation of transdermal absorbability was performed by the following method. 6 parts of 1cm x 1cm are provided in the inner part of the forearm of 10 panelists, 7μL of the test sample, which is the composition prepared above, is applied to each panel and left at 20 ° C for 1 hour, then impregnated with tetrahydrofuran (THF) The skin was wiped off with the absorbent cotton soaked, this absorbent cotton was extracted three times with 100 ml of THF, and the recovered amount of centaureidine derived from Achillea millefolium extract was quantified by high performance liquid chromatography. The transdermal absorbability was evaluated by setting the first applied THF as 100% and reducing the recovery rate from the percutaneous absorbability (the higher the value, the higher the transdermal absorbability). Each test sample was evaluated twice and the average is shown in Table 2.

<Test Example 2 Transdermal absorbability evaluation B of composition>
Each component was mixed by the ratio (mass%) shown in Table 3, and the composition which concerns on each Experimental example 1B-6B was obtained.
Evaluation of transdermal absorbability was performed in the same manner as in Test Example 1. Each test sample was evaluated twice and the average is shown in Table 3. From Table 3, it can be seen that even in the case of a composition containing a polyhydric alcohol, the phase state changes depending on the amount of water.

<Test Example 3 Composition Stability Test>
Each component was mixed by the ratio (mass%) shown in Table 4, and the composition concerning Experimental example C and Comparative experimental example C was obtained.
These prepared compositions were stored at 50 ° C., and after 6 days, stored at 20 ° C. for 24 hours, and the appearance was evaluated. The evaluation criteria are shown below.
<Standard>
0: Uniform transparent appearance.
1: Uniform but translucent appearance.
2: The entire appearance is opaque.
3: There are transparent, translucent and opaque parts, and the appearance is uneven.

<Test Example 4 Effect of Improvement in Skin Roughness of Composition>
The application site | part of the composition was created in the upper arm inner side part of five panelists. A rough skin condition was created by applying a 0.5% aqueous solution of sodium lauryl sulfate (SLS) to this application site for 24 hours. Next, the compositions of Experimental Example C and Comparative Experimental Example C were applied twice a day for a week.
After application of SLS, the application site after application of the composition for one week was photographed with a 50 × video microscope, and the image was taken into a personal computer. Both images were compared, and the improvement condition of rough skin was evaluated according to the following criteria by five skilled evaluation documents. An average value of the evaluation results of five evaluators with respect to five panelists was obtained and used as a rough skin improvement score of the composition. The results are shown below. A higher score value indicates that the composition is more excellent in improving rough skin.

-Evaluation criteria-
5 points that the skin roughness is remarkably improved,
4 points that have been improved,
3 points that are slightly improved,
2 points that are slightly improved,
No improvement at all
-Evaluation results-
Experimental Example C 4.8
Comparative Experimental Example C 3.4

<Test Example 5 Penetration test>
Compositions A (20) to E (20) having a water content of 20% were prepared with the compositions shown in Table 5 below. Further, compositions A (70) to E (70) having a water content of 70% were prepared with the compositions shown in Table 6 below.
Palmitic acid, ceramide, and cholesterol were heated and cooled at 120 ° C. to obtain an intercellular lipid model. Next, what mixed the intercellular lipid model and the said sample by 1: 1 was used for the measurement of a differential calorimeter (DSC), and the value of the enthalpy of the endothermic peak around 52 degreeC obtained is shown in Table 5.
The fluctuation of the intercellular lipid model, that is, the affinity with the intercellular lipid was evaluated based on the size of the intercellular lipid enthalpy. That is, the smaller the value, the higher the affinity between the composition and the intercellular lipid.

  Next, the penetration test of the epidermis was carried out using a commercially available three-dimensional cultured epidermis (manufactured by Japan Tissue Engineering Co., Ltd.) in which the stratum corneum is immature and considered to be only the epidermis living cell layer. As a marker, calcein, a hydrophilic fluorescent probe, was added to Composition A (70) to Composition E (70) prepared above so that the final concentration was 30 mmol / L, and the epidermis was applied 12 hours after application of each composition. Permeability was evaluated by the amount of calcein that permeated and reached the receiver solution. The results are shown in Table 6.

Finally, using a commercially available cultured skin model with a mature stratum corneum (manufactured by Japan Tissue Engineering Co., Ltd.), the following amphiphile aggregates 1 and 2 containing calcein were applied from the outside of the epidermis. After 24 hours, the amount of calcein leaking inside the epidermis was measured.
The results are shown in FIG.
Amphiphilic substance assembly 1; bis (γ-N-lauroylglutamyl) lysine sodium salt 50: diglyceryl oleate 50 (mass ratio)
Amphiphilic substance aggregate 2; bis (γ-N-lauroylglutamyl) lysine sodium salt 20: diglyceryl oleate 80 (mass ratio)

  From these results, a hydrophobic aggregate is formed in a water amount environment of at least one point out of a water amount of 15% or more and 40% or less, and the water amount of at least one point out of a water amount of 65% or more and 75% or less A surfactant complex that forms a hydrophilic aggregate under the environment has extremely high permeability to the entire epidermis, and is useful as a vehicle for carrying an active ingredient in an external preparation for skin.

Claims (7)

A skin external preparation containing a plurality of types of surfactants,
The plurality of types of surfactants form a hydrophobic aggregate in a moisture content environment of at least one of a moisture content of 15% or more and 40% or less, and at least one of a moisture content of 65% or more and 75% or less. A topical skin preparation characterized by forming a hydrophilic aggregate in a point moisture content environment.   The skin external preparation according to claim 1, wherein the hydrophobic aggregate formed by the plurality of types of surfactants is a cubic liquid crystal phase, and the hydrophilic aggregate formed by the plurality of types of surfactants is a D phase. .   The plural kinds of surfactants are 1) one or more selected from the group consisting of α, ε-bis (γ-N- (C10-30) acylglutamyl) lysine and salts thereof, and 2) glycerin. The skin external preparation of Claim 1 or 2 containing 1 or more types selected from the group which consists of fatty acid ester, polyglycerol fatty acid ester, and pyroglutamic acid glycerol fatty acid ester.   The external preparation for skin according to claim 3, wherein the ratio of the 1) component to the 2) component is from 3: 4 to 6: 1.   The skin external preparation according to any one of claims 1 to 4, wherein the plurality of types of surfactants can further form micelles. A cosmetic composition containing a plurality of types of surfactants and a polyhydric alcohol,
The plurality of types of surfactants form a hydrophobic aggregate in a water amount environment of at least one of a water amount of 15% or more and 40% or less, and in an environment of a water amount of 65% or more and 75% or less. A cosmetic composition characterized by forming a hydrophilic aggregate. A quasi-drug composition comprising a plurality of types of surfactants and a polyhydric alcohol,
The plurality of types of surfactants form a hydrophobic aggregate in a water amount environment of at least one of a water amount of 15% or more and 40% or less, and in an environment of a water amount of 65% or more and 75% or less. A quasi-drug composition characterized in that it forms a hydrophilic aggregate.