JP6863548B2 - Cosmetic base for improving skin condition and its screening method - Google Patents

Description

The present invention relates to a method for screening a cosmetic base.

As the base of external preparations for skin such as cosmetics, there are various compounding ingredients and dosage forms.
The base usually plays the role of a matrix holding the active ingredient, or plays a role of producing a feeling such as smoothness and refreshing feeling when applied to the skin. That is, it is not expected to have an effect on the skin by itself.

One of the main dosage forms of cosmetics is the oil-in-water (O / W) emulsifier type. It consists of an emulsion in which the dispersed phase is oil and the continuous phase is water. In general, since the properties of emulsions strongly show the properties of continuous phases, oil-in-water emulsions dissolve in water, spread well, and provide cosmetics with a refreshing feel. Therefore, it is widely used as a base for cosmetics such as milky lotions and creams.

By the way, in healthy skin, there are gaps between cells of the stratum corneum that hold intercellular lipids, and the stratum corneum has a cage shape (Non-Patent Document 1). Such a state is a basket weave (Basket w)
eave) Also called the stratum corneum. On the other hand, in abnormal skin due to dermatitis, xerosis, etc., the stratum corneum cells are in a state of being adhered without gaps (compact stratum corneum).
In the compact stratum corneum, cell adhesion factors are present on the entire surface of the stratum corneum cells, and the stratum corneum cells adhere firmly to each other on the surface, whereas in the basket weave stratum corneum, the cells adhere only to the margins of the stratum corneum cells. It is known that a factor exists and forms a gap as a result of adhesion between the ends of stratum corneum cells (Non-Patent Documents 2 and 3). It is disclosed that cell adhesion factor is detected from a stratum corneum sample exfoliated and collected from a subject to evaluate epidermal turnover and skin condition (Patent Document 1).

JP-A-2007-199053

New Dermatology (Hiroshi Shimizu, Nakayama Shoten), p.38 Journal of Dermatological Science 57 (2010) 192-198 Journal of Dermatology 37 (2010) 873-881

As described above, conventionally, the base has been required to have a role of a matrix and a role of producing a feeling of use, and it has not been expected to have an action effect on the skin by itself.
However, if the base of the cosmetic itself has an effect on the skin, it is not a mere matrix but has added value. In addition, if a base having a skin condition improving action can be adopted as an action on the skin, the range of prescription design of cosmetics will be expanded.
In view of such a situation, it is an object of the present invention to provide a cosmetic base which itself exerts a skin condition improving effect and is suitable for skin condition improving applications. Further, in searching for such a base, it is also an object to provide a non-invasive and simple screening method.

As a result of diligent research to solve the above problems, the present inventors promoted the formation of basket weave-like stratum corneum in the skin, and in such skin, the stratum corneum water content and skin flexibility. , It has been found that the skin condition such as skin color improvement, component storage / permeability improvement, and texture is improved, and the present invention relating to a cosmetic base for skin condition improvement has been completed.
In addition, unlike normal skin, the present inventors did not observe the formation of basket stratum corneum in the three-dimensional cultured skin model, but when the oil-in-water emulsion was applied, the corners were densely packed at the initial stage of culture. It has been found that the formation of the basket weave stratum corneum is promoted from the layer, and the skin model has a stratum corneum structure close to that of normal skin, and the present invention relating to the screening method has also been completed.

That is, the present invention is as follows.
[1] A cosmetic base for improving skin condition, which is characterized by being an oil-in-water emulsifier type.
[2] The cosmetic base for improving skin condition according to [1], which contains a polyhydric alcohol.
[3] The improvement of the skin condition is selected from the group consisting of an increase in the amount of water in the stratum corneum, an improvement in skin flexibility, an improvement in skin color, an improvement in component retention / permeability, and an improvement in texture, according to [1] or [2]. Cosmetic base for improving skin condition.
[4] A cosmetic containing the skin condition improving cosmetic base according to any one of [1] to [3] as a skin condition improving ingredient.
[5] A method for screening a cosmetic base for improving skin condition, using the formation of a basket weave stratum corneum in cultured skin as an index.
[6] The screening method according to [5], which comprises a step of evaluating the basket weave stratum corneum formation by observing a cross section of the cultured skin or detecting a stratum corneum protein in the cultured skin. [7] The improvement of the skin condition is selected from the group consisting of an increase in the amount of water in the stratum corneum, an improvement in skin flexibility, an improvement in skin color, an improvement in component retention / permeability, and an improvement in texture, according to [5] or [6]. Screening method.

INDUSTRIAL APPLICABILITY The present invention provides a cosmetic base that itself exerts a skin condition improving effect. In addition, a screening method that can easily search for a cosmetic base for improving skin condition is provided.

Cross-sectional photograph (HE staining) of a three-dimensional cultured skin model to which the bases of Examples and Comparative Examples were applied. The graph which shows the water content of the stratum corneum before and after the continuous use of the base of Example 3. The graph which shows the stratum corneum flexibility before and after continuous use of the base of Example 3. FIG. Video microscope photographs of the skin surface before and after continuous use of the base of Example 3. Confocal laser scanning micrographs of desmoglein 1 immunostained stratum corneum cells before and after continuous use of the base of Example 3. The graph which shows the number of detected pixels of desmoglein 1 per stratum corneum cell before and after continuous use of the base of Example 3. FIG. Comparison of skin light diffusivity before and after continuous use of the base of Example 3. (A) Graph showing haze, (b) Optical microscope bright-field photograph (black circle is placed in the center of the image to make it easier to see the difference). A graph showing the correlation between the brightness of skin color and the basket weave stratum corneum. A graph showing the correlation between stratum corneum flexibility and basket weave stratum corneum. A graph showing the correlation between stratum corneum flexibility and basket weave stratum corneum. Cross-sectional photographs of a three-dimensional cultured skin model to which pigment was added before and after continuous use of the base of Example 3.

<Cosmetic base for improving skin condition of the present invention>
The cosmetic base for improving skin condition of the present invention is characterized by being an oil-in-water emulsifier type.
Here, the oil emulsifier type in water is not limited to a simple O / W type emulsion, _{and may be a composite emulsion such as (O 1} + O ₂ ) / W type or (W / O) / W type.
The emulsion particles are not particularly limited, but those having an average particle size of 0.1 to 10 μm are preferable because they have excellent basket weave stratum corneum forming ability and a good skin condition improving effect can be obtained.

The cosmetic base for improving skin condition of the present invention is usually composed of a formulation containing an oil phase component, an aqueous phase component, and a surfactant.
The oil phase component is usually composed of an oil component, and the oil component is not limited to a so-called oil agent, but is a component that is suspended in water at 25 to 65 ° C. and allowed to stand for 1 hour and then phase-separated from water (excluding surfactants). Point to.
Oily components that can be blended in the cosmetic base for improving skin condition of the present invention include oils such as polar oils, non-polar oils, silicone oils, natural fats and oils, and hydrocarbon oils; ultraviolet rays such as ultraviolet absorbers and ultraviolet scattering agents. Protective agents: Oil-soluble vitamins such as vitamin A and vitamin E can be mentioned.
The cosmetic base for improving skin condition of the present invention contains an oil agent in an amount of preferably 1 to 70% by mass, more preferably 3 to 50% by mass, still more preferably 5 to 40% by mass, based on the whole base. By using an oil-in-water emulsifier type containing an oil agent in the internal phase in such a range, the basket weave stratum corneum forming ability is further enhanced.

Among the oils, polar oils include isopropyl myristate, cetyl octanate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, and dimethyloctanoic acid. Hexyldecyl, cetyl lactate, myristyl lactate, lanolin acetate, isocetyl stearate, isosetyl isostearate, cholesteryl 12-hydroxystearyl, ethylene glycol di-2-ethylhexylate, dipentaerythritol fatty acid ester, N-alkylglycol monoisostearate, Neopentyl glycol dicaprate, diisostearyl malate, glycerin di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexylate, trimethylolpropane tri-2-ethylhexylate, pentanerythritol tetra-2-ethylhexylate, tri-2 -Glyceryl ethylhexanate, Trimethylolpropane triisostearate, Cetyl 2-ethylhexanoate, 2-Ethylhexyl palmitate, Glycerin trimyristate, Glyceride tri-2-heptylundecanoic acid, Methyl ester of castor oil fatty acid, Oleic acid oil , Cetostearyl alcohol, acetoglyceride, 2-heptyl undecyl palmitate, diisobutyl adipate, N-lauroyl-L-glutamic acid-2-octyldodecyl ester, di-2-heptyl undecyl adipate, ethyl laurate, sebatic acid Di-2-ethylhexyl, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebatate, 2-ethylhexyl succinate, ethyl acetate, butyl acetate, amyl acetate, triethyl citrate, Examples thereof include octylmethoxycinnamate.

Examples of the non-polar silicone oil include cyclopentasiloxane, decamethylcyclopentasiloxane, caprylylmethicone, dimethicone, (dimethicone / vinyldimethicone) crosspolymer, (dimethicone / phenylvinyldimethicone) crosspolymer and the like.
Examples of the polar silicone oil include diphenylsiloxyphenyl trimeticone and the like.
Natural fats and oils include avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat germ oil, southern ka oil, castor oil, flaxseed oil, saflower. Oil, cotton seed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, cinnamon oil, Japanese millet oil, jojoba oil, germ oil, triglycerin, glycerin trioctanoate, glycerin triisopalmitate, etc. Can be mentioned.
Examples of the hydrocarbon oil include isododecane, isohexadecane, squalane, petrolatum, hydrogenated poly (C6-12 olefin), hydrogenated polyisobutene and the like.

The aqueous phase component is not particularly limited as long as it is a water-soluble component in addition to water, and examples thereof include polyhydric alcohols and higher alcohols. The higher alcohol refers to an alcohol having 16 to 22 carbon atoms, preferably 18 to 22 carbon atoms.

The cosmetic base for improving skin condition of the present invention preferably contains a polyhydric alcohol among the aqueous phase components. By containing the polyhydric alcohol, the basket weave stratum corneum forming ability is further enhanced.
The polyhydric alcohol is not particularly limited as long as it is divalent or higher, but trihydric or higher is preferable. Specifically, divalent alcohols (eg, ethylene glycol, propylene glycol, trimethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, tetramethylene glycol, 2,3-butylene glycol, pentamethylene glycol). , 2-Buten-1,4-diol, hexylene glycol, octylene glycol, etc.; trivalent alcohol (eg, glycerin, trimethylolpropane, etc.); tetravalent alcohol (eg, 1,2,6-hexanetriol, etc.) Etc. Pentaerythritol, etc.); pentavalent alcohol (eg, xylitol, etc.); hexavalent alcohol (eg, sorbitol, mannitol, etc.); polyhydric alcohol polymer (eg, diethylene glycol, dipropylene glycol, triethylene glycol, polypropylene glycol, etc.) Tetraethylene glycol, diglycerin, polyethylene glycol, triglycerin, tetraglycerin, polyglycerin, etc.); divalent alcohol alkyl ethers (eg, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol mono) Phenyl ether, ethylene glycol monohexyl ether, ethylene glycol mono2-methylhexyl ether, ethylene glycol isoamyl ether, ethylene glycol benzyl ether, ethylene glycol isopropyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, etc.); 2 Valuable alcohol alkyl ethers (eg, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol butyl ether, diethylene glycol methyl ethyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, propylene Glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, propylene glycol isopropyl ether, dipropylene glycol methyl ether, dipropylene glycol ethyl ether, dipropylene glycol butyl ether, etc. ); Divalent alcohol ether ester (eg, ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether acetate, ethylene glycol monophenyl ether acetate, ethylene glycol diazibate, ethylene glycol dissuccinate, diethylene glycol mono). Ethyl ether acetate, diethylene glycol monobutyl ether acetate, propylene glycol monomethyl ether acetate, propylene glycol monoethyl ether acetate, propylene glycol monopropyl ether acetate, propylene glycol monophenyl ether acetate, etc.); Alcohol, batyl alcohol, etc.);
Sugar alcohols (eg, sorbitol, martitol, maltotriose, mannitol, sucrose, erythritol, glucose, fructose, starch-degrading sugar, maltose, xylitos, starch-degrading sugar-reducing alcohol, etc.); glyceroli; tetrahydrofurfuryl alcohol; POE-tetrahydrofurfuryl alcohol; POP-butyl ether; POP / POE-butyl ether; tripolyoxypropylene glycerin ether; POP-glycerin ether; POP-glycerin ether phosphoric acid; POP / POE-pentaneerythritol ether and the like. One type or a combination of two or more types can be combined.
Of these, glycerin, diglycerin, dipropylene glycol, and polyethylene glycol having a molecular weight of 600 or less are more preferable.
The cosmetic base for improving skin condition of the present invention contains a polyhydric alcohol in an amount of preferably 1 to 40% by mass, more preferably 5 to 40% by mass, still more preferably 10 to 30% by mass, based on the whole base. Particularly preferably, it contains 15 to 30% by mass.

The higher alcohol is usually an aliphatic alcohol, which may or may not be branched and may be saturated or unsaturated. Also, it is preferably a monohydric alcohol. For example, bacil alcohol, setanol, palmitrail alcohol, heptadecanol, 1-heptadecanol, stearyl alcohol, isostearyl alcohol, ellaidyl alcohol, oleyl alcohol, linoleil alcohol, elelide linoleil alcohol, linolenyl alcohol, Elyde linolenic alcohol, ricinorail alcohol, nonadecil alcohol, arachidyl alcohol, heneicosanol, behenyl alcohol, and elcil alcohol are mentioned, and behenyl alcohol, stearyl alcohol, and arachidyl alcohol are particularly preferable. In addition, these one kind or two or more kinds can be combined.
The cosmetic base for improving skin condition of the present invention contains a higher alcohol, preferably 0 to 5% by mass, more preferably 0.1 to 5% by mass, still more preferably 0.5 to 3% by mass, based on the whole base. Contains% by mass.

Examples of the surfactant include anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, silicone-based surfactants, and the like, and are not particularly limited.
In the cosmetic base for improving skin condition of the present invention, the surfactant is preferably 0.1 to 7% by mass, more preferably 0.5 to 5% by mass, still more preferably 1 to 1% by mass based on the whole base. Contains 5% by mass.

Examples of the anionic surfactant include fatty acid sulphates (eg, sodium laurate, sodium palmitate, etc.); higher alkyl sulfates (eg, sodium lauryl sulfate, potassium lauryl sulfate, etc.); alkyl ether sulfates (eg, sodium lauryl sulfate, etc.). POE lauryl sulfate triethanolamine, POE sodium lauryl sulfate, etc.); N-acylsarcosic acid (eg, sodium lauroyl sarcosin, etc.); higher fatty acid amide sulfonate (eg, N-myristoyl-N-methyltaurine sodium, coconut oil fatty acid, etc.) Methyl taurid sodium, lauryl methyl taurid sodium, etc.); Phosphate ester salts (POE oleyl ether phosphate sodium, POE stearyl ether phosphoric acid, etc.); Sulfon succinates (eg, di-2-ethylhexyl sulfosuccinate sodium, monolauroyl, etc.) Monoethanolamide polyoxyethylene sodium sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate, etc.); Alkylbenzene sulfonate (eg, sodium linadodecylbenzene sulfonate, linadodecylbenzene sulfonate triethanolamine, linadodecylbenzene sulfonic acid, etc.); Higher fatty acid ester sulfate ester salts (eg, cured coconut oil fatty acid sodium glycerin sulfate, etc.); N-acylglutamate (eg, N-lauroyl glutamate monosodium, N-stearoyl glutamate disodium, N-myristoyl-L-glutamate monosodium) Etc.); Sulfated oil (eg, funnel oil, etc.); POE alkyl ether carboxylic acid; POE alkyl allyl ether sulfonate; α-olefin sulfonate; higher fatty acid ester sulfonate; secondary alcohol sulfate ester salt; higher Examples thereof include fatty acid alkylolamide sulfate ester salt; sodium lauroyl monoethanolamide succinate; N-palmitoyl aspartate ditriethanolamine; sodium caseinate and the like.

Examples of the cationic surfactant include alkyltrimethylammonium salts (eg, stearyltrimethylammonium chloride, lauryltrimethylammonium chloride, etc.); alkylpyridinium salts (eg, cetylpyridinium chloride, etc.); distearyldimethylammonium chloride dialkyldimethylammonium salts; Polychloride (N, N'-dimethyl-3
, 5-Methylene piperidinium); alkyl quaternary ammonium salt; alkyldimethylbenzylammonium salt; alkylisoquinolinium salt; dialkylmoriphonium salt; POE alkylamine; alkylamine salt; polyamine fatty acid derivative; amyl alcohol fatty acid derivative Benzalkonium chloride; benzethonium chloride and the like.

Examples of the amphoteric tenside include imidazoline-based amphoteric tenside agents (for example, 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazolin sodium, 2-cocoyl-2-imidazolinium hydroki. Side-1-carboxyethyroxy disodium salt, etc.); Betaine-based surfactants (eg, 2-heptadecyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkyl betaine, amide betaine) , Sulfobetaine, etc.) and the like.

Examples of the nonionic surfactant include sorbitan fatty acid esters (for example, sorbitan monooleate, sorbitan monostearate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesqui). Oleate, sorbitan trioleate, penta-2-ethylhexylate diglycerol sorbitan, tetra-2-ethylhexylate diglycerol sorbitan, etc.); glycerin fatty acids (for example, monocotton seed oil fatty acid glycerin, monoerucate glycerin, sesquioleate glycerin, mono Glycerin stearate, α, α'-glycerin pyroglutamate oleate, glycerin monostearate, malic acid, etc.); propylene glycol fatty acid esters (for example, propylene glycol monostearate, etc.); POE castor oil / cured castor oil derivative (POE) Himasi oil, POE-hardened Himashima oil, etc.); Examples thereof include oil-based substances such as glycerin alkyl ether.
Also, as hydrophilic ones, for example, polyglycerin fatty acid esters (for example, polyglyceryl monooleate, polyglyceryl monostearate, etc.); POE sorbitan fatty acid esters (for example, POE sorbitan monooleate, POE sorbitan monostearate, etc.). POE sorbitan tetraoleate, etc.); POE sorbit fatty acid esters (eg, POE sorbit monolaurate, POE sorbit monooleate, POE sorbit pentaoleate, POE sorbit monostearate, etc.); POE glycerin fatty acid esters (eg, POE glycerin fatty acid esters, etc.) POE glycerin monostearate, POE glycerin monoisostearate, POE monooleate such as POE glycerin triisostearate); POE fatty acid esters (eg, POE distearate, POE monostearate, POE monodiolate, ethylene glycol distearate, etc.) POE alkyl ethers (eg, POE lauryl ether, POE oleyl ether, POE stearyl ether, POE-behenyl ether, POE-2-octyldodecyl ether, POE cholestanol ether, etc.); POE alkylphenyl ethers (eg, POE nonyl) Phenyl ether, etc.); Pluronic type (eg, Pluronic, etc.); POE / POP alkyl ethers (eg, POE / POP cetyl ether, POE / POP-2-decyltetradecyl ether, POE / POP monobutyl ether, POE / POP Hydrogenated lanolin, POE / POP glycerin ether, etc.); Tetra POE / Tetra POP
Ethylenediamine condensates (eg, Tetronic, etc.); POE castor oil hardened castor oil derivatives (eg, POE castor oil, POE hardened castor oil, POE hardened castor oil monoisostearate, POE hardened castor oil triisostearate, POE Hardened castor oil monopyroglutamic acid monoisostearic acid diester, POE hardened castor oil maleic acid, etc.; POE castor lanolin derivatives (eg, POE sorbit honeybee, etc.); alkanolamides (eg, coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, etc.) , Fatty acid isopropanolamide, etc.); POE propylene glycol fatty acid ester; POE alkylamine; POE fatty acid amide; sucrose fatty acid ester; alkyl glucoside; alkyl ethoxydimethylamine oxide; trioleyl phosphate and the like.

The cosmetic base for improving skin condition of the present invention may optionally contain other ingredients usually used for a cosmetic base as long as the effects of the present invention are not impaired. Such optional components include, for example, moisturizers, preservatives, powder components, metal ion sequestering agents, lower alcohols, monosaccharides, oligosaccharides, polysaccharides, amino acids, organic amines, polymer emulsions, pH adjusters, antioxidants, etc. Examples include organic modified clay minerals.

Moisturizers include, for example, polyethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, xylitol, sorbitol, martitol, chondroitin sulfate, hyaluronic acid, mucoitin sulfate, caronic acid, atelocollagen, cholesteryl-12-hydroxystearate. , Sodium lactate, bile acid salt, dl-pyrrolidone carboxylate, short chain soluble collagen, diglycerin (EO) PO adduct, Izayoi rose extract, Xylitol extract, melilot extract and the like.
Examples of the preservative include ethylparaben, butylparaben and the like.

Examples of the powder component include inorganic powders (for example, talc, kaolin, mica, silk mica (serisite), white mica, gold mica, synthetic mica, red mica, black mica, permiculite, magnesium carbonate, calcium carbonate, silicic acid. Aluminum, barium silicate, calcium silicate, magnesium silicate, strontium silicate, metal tungate, magnesium, silica, zeolite, barium sulfate, calcined calcium sulfate (baked sekko), calcium phosphate, fluoroapatite, hydroxyapatite, ceramic powder , Metal soaps (eg zinc myristate, calcium palmitate, aluminum stearate), boron nitride, etc.; Organic powders (eg polyamide resin powder (nylon powder), polyethylene powder, polymethyl methacrylate powder, polystyrene powder, styrene And acrylic acid copolymer resin powder, benzoguanamine resin powder, polytetrafluorinated ethylene powder, cellulose powder, etc.; inorganic white pigments (eg, titanium dioxide, zinc oxide, etc.); inorganic red pigments (eg, iron oxide (eg, iron oxide) Bengala), iron titanate, etc.); Inorganic brown pigments (eg, γ-iron oxide, etc.); Inorganic yellow pigments (eg, yellow iron oxide, ocher, etc.); Inorganic black pigments (eg, black iron oxide, low) (Titanium oxide, etc.); Inorganic purple pigments (eg, mango violet, cobalt violet, etc.); Inorganic green pigments (eg, chromium oxide, chromium hydroxide, cobalt titanate, etc.); Inorganic blue pigments (eg, ultramarine, etc.) Navy blue, etc.); Pearl pigments (eg, titanium oxide coated mica, titanium oxide coated bismuth oxychloride, titanium oxide coated talc, colored titanium oxide coated mica, bismuth oxychloride, fish scale foil, etc.); Metal powder pigments (eg, aluminum powder, Copper powder, etc.); Organic pigments such as zirconium, barium or aluminum lake (eg, Red 201, Red 202, Red 204, Red 205, Red 220, Red 226, Red 228, Red 405, Organic pigments such as Orange 203, Orange 204, Yellow 205, Yellow 401, and Blue 404, Red 3, Red 104, Red 106, Red 227, Red 230, Red 401, Red 505, orange 205, yellow 4, yellow 5, yellow 202, yellow 203, green 3, blue 1, etc.); natural pigments (eg, chlorophyll, β-carotene, etc.) and the like.

Examples of the metal ion sequestering agent include 1-hydroxyethane-1,1-diphosphonic acid, 1-hydroxyethane-1,1-diphosphonic acid tetrasodium salt, disodium edetate, trisodium edetate, and tetrasodium edetate. , Sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, phosphoric acid, citric acid, ascorbic acid, succinic acid, edetic acid, trisodium ethylenediaminehydroxyethyl triacetate and the like.

Examples of the lower alcohol include ethanol, propanol, isopropanol, isobutyl alcohol, t-butyl alcohol and the like.

Examples of the simple sugar include tricarbose (eg, D-glycerylaldehyde, dihydroxyacetone, etc.); tetracarbose (eg, D-erythulose, D-elittlerose, D-treose, erythritol, etc.); , L-arabinose, D-xylulose, L-lyxose, D-arabinose, D-ribose, D-libulose, D-xylulose, L-xylulose, etc.; -Bushicose, D-galactose, D-fructose, L-galactose, L-mannose, D-tagatose, etc.); Seven-carbon sugar (eg, aldoheptose, heprose, etc.); Eight-carbon sugar (eg, octulose, etc.); For example, 2-deoxy-D-ribose, 6-deoxy-L-galactose, 6-deoxy-L-mannose, etc.; amino sugars (eg, D-glucosamine, D-galactosamine, sialic acid, aminouronic acid, muramic acid, etc.) ); Uronic acid (for example, D-glucuronic acid, D-mannuronic acid, L-glulonic acid, D-galacturonic acid, L-isulonic acid, etc.) and the like.

Examples of oligosaccharides include sucrose, gunthianose, umbelliferose, lactose, planteos, isolikunoses, α, α-trehalose, raffinose, lycnoses, umbilicin, stachyose velvas and the like.
Examples of polysaccharides include cellulose, quince seed, chondroitin sulfate, starch, galactan, dermatan sulfate, glycogen, Arabic gum, heparan sulfate, hyaluronic acid, tragant gum, keratane sulfate, chondroitin, xanthan gum, mucoitin sulfate, guagam, dextran, and keratosulfate. , Locust bean gum, succinoglucan, caronic acid and the like.

Examples of amino acids include neutral amino acids (eg, threonine, cysteine, etc.); basic amino acids (eg, hydroxylysine, etc.) and the like. Examples of the amino acid derivative include acyl sarcosine sodium (lauroyl sarcosine sodium), acyl glutamate, acyl β-alanine sodium, glutathione, pyrrolidone carboxylic acid and the like.

Examples of the organic amine include monoethanolamine, diethanolamine, triethanolamine, morpholine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-methyl-1-propanol and the like. Can be mentioned.

Examples of the polymer emulsion include an acrylic resin emulsion, an ethyl polyacrylate emulsion, an acrylic resin liquid, a polyacrylic alkyl ester emulsion, a polyvinyl acetate resin emulsion, and a natural rubber latex.

Examples of the pH adjuster include buffers such as lactic acid-sodium lactate, citric acid-sodium citrate, and succinic acid-sodium succinate.
Examples of vitamins include vitamins A, B1, B2, B6, C, E and their derivatives, pantothenic acid and its derivatives, biotin and the like.

Examples of the antioxidant include tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, gallic acid esters and the like.
Examples of the antioxidant aid include phosphoric acid, citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, kephalin, hexametaphosphate, phytic acid, ethylenediaminetetraacetic acid and the like.

Organically modified clay minerals include, for example, smectite-based (hectorite, bentonite, montmorillonite, etc.), kaolinite, illite, marine clay mineral (sea mud), desert rose clay mineral, pascalite, and other clay minerals, as well as quaternary amine groups. Examples thereof include those modified by a carboxyl group or the like. Examples of commercially available products include "Benton 38V (dimethyl distearyl ammonium-modified hectorite)" (manufactured by Elementis). These are generally used as oil emulsifier type stabilizers in water.

The cosmetic base for improving skin condition of the present invention can be prepared by a usual procedure of oil emulsification in water.

The cosmetic base of the present invention improves the state in which the stratum corneum cells adhere tightly to each other in the skin (compact stratum corneum), and forms a basket weave stratum corneum showing a cage state in which there are gaps between the stratum corneum cells. Facilitate. As shown in Examples described later, in the skin on which the basket weave stratum corneum is formed, the water content of the stratum corneum increases, the skin flexibility is improved, the skin color is improved, and the component retention and permeability are improved. Since the skin condition is improved such as the texture is improved, the cosmetic base of the present invention is suitable for the skin condition improving application. By improving the skin condition, it is possible to suppress the aging of the skin, improve the make-up paste, and give the impression that the skin looks beautiful. The improvement of skin color means that the soft focus effect (blurring effect) gives a good impression of the skin color and texture, and that the skin color becomes brighter (brightness increases). The texture refers to the morphology of the skin surface, and is the fineness of the skin pattern consisting of skin grooves (fine and shallow grooves that run vertically, horizontally and radially on the skin surface) and skin hills (small ridges surrounded by skin grooves). Good or bad is evaluated by roughness and adjustment / distortion.

The skin condition improving cosmetic base of the present invention can be suitably blended in cosmetics as a skin condition improving ingredient. At this time, other optional ingredients can be added to the cosmetics together.
In the production of such cosmetics, other optional ingredients may be added to the skin condition improving cosmetic base of the present invention, or both when emulsifying and preparing the skin condition improving cosmetic base of the present invention. It may be mixed.
Other optional components include, for example; anti-inflammatory agents (eg, glycyrrhizinic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokithiol, zinc oxide, allantin, etc.); whitening agents (eg, placenta extract, yukinoshita extract, arbutin, etc.) ); Various extracts (eg, Oubaku, Ouren, Shikon, Shakuyaku, Senburi, Birch, Sage, Biwa, Carrot, Aloe, Zeniaoi, Iris, Grape, Yokuinin, Hechima, Yuri, Saffron, Senkyu, Shokyu, Otogirisou, Ononis , Carrots, peppers, tinctures, tinctures, seaweeds, etc.), activators (eg, royal jelly, photosensitizers, cholesterol derivatives, etc.); blood circulation promoters (eg, nonylate valenylamide, nicotinic acid benzyl ester, nicotinic acid β-butoxyethyl ester) , Capsaicin, Zingeron, Cantaristinki, Ictamoll, Tannic acid, α-Bornooleol, Tocopherol nicotinate, Inositol hexanicotinate, Cyclanderate, Cinnaridine, Trazoline, Acetylcholine, Verapamil, Cepharantin, γ-Oryzanol, etc.); Agents (eg, sulfur, thiantoll, etc.); Anti-inflammatory agents (eg, tranexamic acid, thiotaurine, hypotaurine, etc.) and the like.

<Screening method of the present invention>
The screening method of the present invention is a basket weave in cultured skin.
Weave) This is a screening method for a cosmetic base for improving skin condition, using the formation of the stratum corneum as an index.
Since this screening method is performed in vitro using cultured skin, screening can be performed non-invasively without collecting a skin sample from the subject.
The cultured skin used for screening may be one obtained by culturing skin collected from a living body, or one cultivated and constructed as a three-dimensional cultured skin model.
When using cultured skin collected from a living body and cultured, it is preferable that the stratum corneum is in an immature state.
As the three-dimensional cultured skin model, those cultured and constructed from normal human epidermal keratinocytes having a stratum granulosum, a stratum spinosum, and a stratum spinosum from the basal layer of the basic epidermal structure can be preferably used, for example, a commercially available EPI. -200 kits (Mattek) etc. can be used.
Unlike normal skin, cultured skin with immature stratum corneum and three-dimensional cultured skin model have a compact stratum corneum instead of basket weave stratum corneum, but a cosmetic base having a skin condition improving effect. Based on the fact that basket weave stratum corneum formation is promoted by applying the above and that there is a correlation between basket weave stratum corneum formation and skin condition, the formation can be used as an index for screening.
The term "improvement of skin condition" as used herein refers to an increase in the amount of water in the stratum corneum, an improvement in skin flexibility, an improvement in skin color, an improvement in component retention / permeability, and / or an improvement in texture.

As an example of a specific screening procedure, a test sample is added to cultured skin precultured according to a conventional method, and after further culturing at room temperature for 4 to 48 hours, basket weave stratum corneum formation in the cultured skin is evaluated. ..

Evaluation of basket weave stratum corneum formation can be performed by observing the cross section of the cultured skin. For example, a section of the cultured skin after completion of the culture may be prepared by a conventional method, stained with hematoxylin eosin (HE) or the like, and then observed with an optical microscope or the like.
In this case, in the section prepared from paraffin embedding, the distance from the top to the bottom of the stratum corneum (corneal layer distance) is preferably 110% or more, more preferably 120, with respect to the stratum corneum distance in the case of no treatment. When it is% or more, it can be judged that the test sample promotes basket weave stratum corneum formation. Alternatively, the observation image of only the stratum corneum portion of the HE-stained image is cut out, and after binarization processing, the ratio of the number of white pixels (corresponding to the gap between the stratum corneum cells) to the total number of pixels is calculated to calculate the angle. The ratio of the gap in the entire layer is calculated, and when the ratio is preferably 15% or more, more preferably 25% or more, still more preferably 40% or more, it is determined that the test sample promotes basket weave stratum corneum formation. be able to.

It is also possible to evaluate basket weave stratum corneum formation by detecting stratum corneum proteins in cultured skin. For example, the stratum corneum protein may be detected from the stratum corneum sample collected by performing tape stripping on the surface of the cultured skin after the completion of the culture, and more preferably, the distribution thereof is acquired by an image. Examples of the stratum corneum protein include cell adhesion proteins, stratum corneum substances, stratum corneum cell constituents, etc., preferably a stratum corneum cell adhesion factor (corneodesmosome), and more preferably desmoglein, which is a constituent protein thereof. ..
As the detection method, for example, the method described in JP-A-2007-199053 by immunostaining of stratum corneum protein is preferable.
In this case, for example, it is observed whether the distribution of the fluorescently detected stratum corneum protein is unevenly distributed on the entire surface of the stratum corneum cells or on the marginal portion of the stratum corneum cells, and when it is unevenly distributed on the marginal portion. , The test sample can be determined to promote basket weave stratum corneum formation. Alternatively, when a stratum corneum protein such as desmoglein is reduced due to the progress of degradation, for example, as in JP-A-2007-199053, the number of pixels of the stratum corneum protein detected by fluorescence per stratum corneum cell is determined. When counted, preferably 90% or less, more preferably 80% or less of the untreated case, it can be determined that the test sample promotes basket weave stratum corneum formation.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples as long as the gist thereof is not exceeded.

<Manufacturing example>
The oil-in-water emulsifier-type compositions of Examples 1 to 4 were produced according to the formulations shown in Table 1. That is, after each of the A component, the B component, and the C component was heated and dissolved, the A component and then the B component were gradually added to the C component with stirring and emulsified to obtain an oil-in-water emulsified composition. The content of the polyhydric alcohol is 10.0% in Example 1 and 18.0% in Examples 2 to 4. Regarding the type of oil, Examples 1 to 3 contained seed oil of Medfoam, which is a polar oil, but Example 4 changed this to squalane, which is a non-polar oil.
A water-in-oil emulsifier type composition of Comparative Example 1 was produced according to the formulation shown in Table 2. That is, after each of the D component and the E component was heated and dissolved, the E component was gradually added to the D component with stirring and emulsified to obtain a water emulsified composition in oil.
In addition, Vaseline (manufactured by Taiyo Pharmaceutical Co., Ltd.) was prepared as Comparative Example 2.

<Test Example 1> In vitro screening using a 3D cultured skin model A test was conducted using a commercially available 3D cultured skin model (EPI-200 kit, Mattek). The skin model is cultured according to the method of using the kit, and 100 μL of the compositions of Examples 1 to 5 and Comparative Examples 1 and 2 are added as test substances in each cup (on the stratum corneum) of the skin model at room temperature. The cells were cultured for 4 to 48 hours. After completion of the culture, the cultured skin model was washed with PBS (-), fixed with a 10% neutral buffered formalin solution, embedded in paraffin, and tissue sections were prepared as usual. In addition, as a control, an untreated skin model was also cultured in the same manner to prepare tissue sections. Each tissue section prepared was stained with hematoxylin eosin (HE), and the tissue structure of the stratum corneum was observed by optical microscope observation (Fig. 1). The stratum corneum distance was measured using imaging of the stained stratum corneum, and the ratio to the untreated stratum corneum was calculated (Table 3). Further, in the image of the binarized stratum corneum portion, the ratio of the number of white pixels to the total number of pixels was calculated and used as the ratio of the gap to the entire stratum corneum (Table 3).

As shown in FIGS. 1 and 3, in the untreated skin model (control), the stratum corneum cells adhered without gaps, whereas the skin to which the oil-in-water emulsifier-type composition of Examples 1 to 4 was added was added. In the model, it was confirmed that the gap between the stratum corneum cells was formed and the distance between the stratum corneum was increased, and the formation of the basket weave stratum corneum was promoted. In particular, Examples 2 to 4 containing 18.0% by mass of the polyhydric alcohol had a larger proportion of gaps in the stratum corneum than Example 1 containing 10% by mass, and the formation of the basket weave stratum corneum proceeded. There was. In the skin model to which the water-in-oil emulsifier type composition of Comparative Example 1 and Vaseline of Comparative Example 2 were added, the formation of the basket weave stratum corneum was not observed as in the untreated control skin model.
From these results, it was shown that the oil-in-water emulsifier-type base is effective in forming the basket weave stratum corneum, and it is more preferable to contain a specific amount of polyhydric alcohol.

<Test Example 2> Continuous use test of an oil-in-water emulsifier-type base for humans The oil-in-water emulsion formulation of Example 3 was used twice a day for 22 female subjects in their 30s and 40s for one month continuously. I got it. Before continuous use and after continuous use for 1 month, the water content of the stratum corneum was measured by Skion-200, and the flexibility of the stratum corneum was measured by using Venustron using the frequency change (Δf) under a load of 2 g on the outward path as an index. In addition, the texture of the skin surface (sharpness of the skin groove and the shape of the skin hill) was observed using a video microscope, and the expert scored 5 levels (deterioration, slightly worse, no change, slightly improved, improved). Evaluated in. In addition, immunostaining of desmoglein 1 in the stratum corneum cells collected by tape stripping from the same subject was performed, and the state of formation of the basket weave stratum corneum was examined using the presence status as an index.

For immunostaining of desmoglein 1, Japanese Patent Application Laid-Open No. 2007-199053 and Y. Naoe et al. Journal of Dermatological Science 57 (2010) 192-198 were referred to.
Specifically, using a commercially available adhesive tape, the stratum corneum cells on the cheek of the subject were peeled off and collected using the tape, the tape was attached to a slide glass, and the adhesive tape was removed by treating with xylene for half a day. .. Desmoglein 1 immunostaining was performed on the stratum corneum cells attached to the slide glass. The immunostaining was performed using Anti-Desmogrein 1, Mouse-Mono [Dsg1-P23] (Progen 65110) as the primary antibody and Alexa Fluor 488 Goat Anti-mouse IgG (Invitrogen A-11001) as the secondary antibody. The stained stratum corneum specimen was observed with a confocal laser scanning microscope.

FIG. 2 shows the results of the water content of the stratum corneum (average of all subjects). It can be seen that the water content of the stratum corneum increased by the continuous use of the oil-in-water emulsifier type composition of Example 3 for one month.
FIG. 3 shows the results of stratum corneum flexibility (average of all subjects). Since the larger the absolute value of the frequency change Δf [Hz] on the vertical axis, the higher the flexibility, the flexibility of the stratum corneum was improved by the continuous use of the oil-in-water emulsifier type composition of Example 3 for one month. I understand.
FIG. 4 shows an image of the skin surface of one subject. Table 4 shows the results of texture condition evaluation using a 5-point score. It can be seen that the texture condition (sharpness of the skin groove and the shape of the skin hill) was improved by continuous use of the oil-in-water emulsifier type composition of Example 3 for one month.

FIG. 5 shows an imaging of immunostained stratum corneum cells of one subject, desmoglein 1. Further, with reference to Japanese Patent Application Laid-Open No. 2007-199053, the result of counting the number of pixels per fluorescently detected desmoglein 1 per stratum corneum cell is shown in FIG. 6 (average of all subjects). Desmoglein 1, which was present on the entire cell surface before the one-month continuous use of the oil-in-water emulsifier-type composition of Example 3, was decomposed and remained only at the cell margin after the one-month continuous use. The situation was observed, and it was confirmed that the expression level of desmoglein 1 per stratum corneum cell was significantly reduced after continuous use as compared with before continuous use. It is considered that the formation of the basket weave stratum corneum was promoted by the continuous use of the oil-in-water emulsifier type composition of Example 3 for one month.

<Test Example 3> Examination of light diffusivity of basket weave stratum corneum A three-dimensional skin model is cultured in the same manner as in Test Example 1, and 100 μL of the composition of Example 3 is placed in each cup (on the stratum corneum) of the skin model. They were added one by one and cultured at room temperature for 24 hours to form a basket weave stratum corneum. For comparison, an unadded composition was also prepared to prepare an immature stratum corneum (compact stratum corneum).
The haze meter NDH5000 (manufactured by Nippon Denshoku Kogyo Co., Ltd.) was used to measure the total light transmittance, diffusion transmittance, and parallel transmittance of the prepared sample, and haze (Haze (%) = diffusion transmittance). / Total light transmittance x 100%) was calculated. The results are shown in FIG. 7 (a).
In addition, the transmitted diffused light was directly photographed with an optical microscope (bright field) in the prepared sample. The results are shown in FIG. 7 (b).

The three-dimensional cultured skin model in which the basket weave stratum corneum was formed showed significantly higher haze than the three-dimensional cultured skin model of the compact stratum corneum, and was shown to be excellent in light diffusivity (FIG. 7 (a)). ). Further, it can be seen from the photographed image of the transmitted diffused light that the basket weave stratum corneum is superior in light diffusing property as compared with the compact stratum corneum (FIG. 7 (b)).
From these results, it was shown that the formation of the basket weave stratum corneum improves the light diffusivity of the skin, and the soft focus effect (blurring effect) may improve the color and texture of the skin.

<Test Example 4> Examination of correlation between basket weave stratum corneum and skin color brightness For 41 female subjects in their 50s to 60s, L * values were measured with a spectrophotometer.
Horn layer cells were collected from the same subject by tape stripping, and immunostaining of desmoglein 1 of the stratum corneum cells was performed in the same manner as in Test Example 2. From the obtained immunostained images, the ratio of the number of pixels showing desmoglein 1 was calculated with respect to the total number of pixels remaining after removing the portion where the stratum corneum cells did not exist. The smaller this value is, the more the decomposition of Corneodesmosome is progressing, that is, the higher the degree of basket weave stratum corneum formation.
Correlation analysis between the L * value and the above ratio was performed using analysis software (JMP ver. 10.0 (manufactured by SAS)).

The results are shown in FIG. It was shown that the higher the degree of basket weave stratum corneum formation, the larger the L * value and the lighter the skin color, as the decomposition of Corneodesmosome progressed. From this result, it was clarified that the formation of the basket weave stratum corneum improves the brightness of the skin color.

<Test Example 5> Examination of correlation between basket weave stratum corneum and stratum corneum flexibility (1)
For 93 female subjects in their 20s to 70s, the flexibility of the stratum corneum was measured by Venustron using the frequency change (Δf) under a load of 2 g on the outward path as an index.
Horn layer cells were collected from the same subject by tape stripping, and immunostaining of desmoglein 1 of the stratum corneum cells was performed in the same manner as in Test Example 2. Each subject was ranked by observing whether the degree of degradation of desmoglein 1 was used as an index, that is, whether the corneodesmosome remaining in the stratum corneum cells was unevenly distributed in the marginal region. The smaller this rank is, the higher the degree of the Corneodesmosome is unevenly distributed in the marginal portion, that is, the higher the degree of basket weave stratum corneum formation.
Correlation analysis between the frequency change (Δf) value and the above rank was performed using analysis software (JMP ver. 10.0 (manufactured by SAS)).

The results are shown in FIG. It was shown that the higher the degree of basket weave stratum corneum formation, the larger the absolute value of the frequency change (Δf) value, and the higher the stratum corneum flexibility, as the decomposition of the corneodesmosome progressed. From this result, it was clarified that the formation of the basket weave horny layer improves the horny layer flexibility.

<Test Example 6> Examination of correlation between basket weave stratum corneum and stratum corneum flexibility (2)
For 98 female subjects in their 20s to 60s, the flexibility of the stratum corneum was measured by Venustron using the frequency change (Δf) under a 2 g load on the outward path as an index.
Horn layer cells were collected from the same subject by tape stripping, and immunostaining of desmoglein 1 of the stratum corneum cells was performed in the same manner as in Test Example 2. From the obtained immunostained image, the ratio of the number of pixels showing desmoglein 1 to the total number of pixels was calculated in the same manner as in Test Example 4.
Correlation analysis between the frequency change (Δf) value and the ratio was performed using analysis software (JMP ver. 10.0 (manufactured by SAS)).

The results are shown in FIG. It was shown that the higher the degree of basket weave stratum corneum formation, the larger the absolute value of the frequency change (Δf) value, and the higher the stratum corneum flexibility, as the decomposition of the corneodesmosome progressed. From this result, it was clarified that the formation of the basket weave horny layer improves the horny layer flexibility.

<Test Example 7> Examination of component retention and permeability of basket weave horny layer Similar to Test Example 3, samples of basket weave horny layer and compact horny layer were prepared using a three-dimensional skin culture model.
To the prepared sample, 100 μL of a dye (0.05% toluidine blue solution) was added and cultured at 37 ° C. After 3 hours, the tissue was collected, frozen and embedded in an OCT compound, and tissue sections were prepared as usual. By observing with an optical microscope, the localization state of the pigment in the epidermis was observed.

The results are shown in FIG. It can be seen that the three-dimensional cultured skin model in which the basket weave stratum corneum is formed has a larger pigment retention in the stratum corneum than the three-dimensional cultured skin model of the compact stratum corneum. In addition, the three-dimensional cultured skin model of the compact stratum corneum did not show pigment penetration into the epidermis layer, but the three-dimensional cultured skin model that formed the basket weave stratum corneum confirmed that the pigment penetrated into the epidermis layer. Was done. From this result, it was shown that the formation of the basket weave stratum corneum may improve the retention and permeability of the active ingredient in the skin.

INDUSTRIAL APPLICABILITY The present invention provides a cosmetic base that itself exerts a skin condition improving effect. In addition, a screening method that can easily search for a cosmetic base for improving skin condition is provided. It is very useful in industry because it adds value to the cosmetic base itself and expands the range of prescription designs for cosmetics.

Claims (2)

A screening method for a cosmetic base for improving skin condition, using basket weave stratum corneum formation in cultured skin as an index.
A method comprising the step of evaluating the basket weave stratum corneum formation by observing a cross section of the cultured skin. The screening method according to claim 1 , wherein the improvement in skin condition is selected from the group consisting of an increase in water content in the stratum corneum, an improvement in skin flexibility, an improvement in skin color, an improvement in component retention / permeability, and an improvement in texture.

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