JP2018108953A - Corneocyte thickening agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an external composition (corneocyte thickening agent) having the effect of thickening corneocytes and giving skin resilience and a puffy feeling.SOLUTION: The corneocyte thickening agent contains higher fatty acid, higher fatty acid salt, and higher alcohol.SELECTED DRAWING: None

Description

  The present invention relates to a keratinocyte thickening agent.

  Many people, especially women, have a desire to “become beautiful skin” at any age, and multiple products and methods have been proposed to fulfill this desire. In particular, aging causes skin softness to decrease, and there is a persistent desire to improve this and restore skin softness.

  The stratum corneum located in the outermost layer of the skin has biologically important functions such as a barrier function and a moisturizing function. As its structure is often compared to blocks and mortar, it is composed of flat corneocytes corresponding to blocks and intercellular lipids corresponding to mortar filling them. Intercellular lipids have a lamellar structure composed of ceramide, cholesterol, free fatty acids, etc., and the barrier function varies greatly due to quantitative or qualitative changes in these lipids, disorder of orientation, etc. It is said to play an important role mainly in the barrier function of the stratum corneum. On the other hand, the keratinocytes are filled with keratin fibers and contain the natural moisturizing factor NMF mainly composed of free amino acids and lactic acid that play an important role in the moisturizing function. It is said that it plays an important role. In addition, keratinocytes are enveloped in a membrane-like structure called a cornified envelope (CE) in which various proteins such as involucrin and loricrin are cross-linked and insolubilized.

  Due to advances in biometric technology, it has recently become possible to non-invasively measure and identify the amount of substances that make up the skin using an in vivo confocal Raman microscope. According to such an in vivo confocal Raman microscope, a moisture profile in the depth method in the stratum corneum, epidermis, or dermis is drawn, and the thickness of the stratum corneum can be evaluated. In addition, a library of components (for example, keratin, ceramide, NMF, water, etc.) constituting the skin is stored in advance in this device, and the amount in the skin can be determined by selecting it during skin measurement. It is also possible to measure (Non-Patent Documents 1 to 3).

Mariko Egawa et al., Acta Derm Venereol 2007; 87: 4-8 Motoji Takahashi “Progress in skin measurement and transdermal absorption of substances”, Drug Delivery System 22-24, 2007 Hiroshi Suzuki “In vivo confocal Raman spectroscopic analysis of skin changes after hand cream application”, COSMETICS STAGE Vol.9, No.6, 2015

  An object of this invention is to provide the agent (keratinocyte thickening agent) which has the effect | action which thickens a keratinocyte and softens skin softly.

  The inventors of the present invention have made extensive studies in order to achieve the above-mentioned object.Unexpectedly, a composition prepared by mixing a saponified product and a higher alcohol, which has been conventionally used as a soap, into a corneocyte. It has been found that it has the effect of thickening and softening the skin.

  The present invention has been completed based on this finding, and has the following embodiments.

(I) A keratinocyte thickening agent (I-1) A keratinocyte thickening agent containing a higher fatty acid, a higher fatty acid salt, and a higher alcohol.
(I-2) The content of higher fatty acid is 5 to 25% by mass, the content of higher fatty acid salt is 2 to 10% by mass, and the content of higher alcohol is 0.5 to 8% by mass. 1) The keratinocyte thickening agent as described.
(I-3) The higher fatty acid and the higher fatty acid of the higher fatty acid salt are the same or different and are saturated or unsaturated fatty acids having 14 to 18 carbon atoms, as described in (I-1) or (I-2) A keratinocyte thickening agent.
(I-4) The keratinocyte thickening agent according to any one of (I-1) to (I-3), wherein the higher alcohol is a saturated or unsaturated monohydric alcohol having 14 to 18 carbon atoms.
(I-5) A keratinocyte thickening agent according to any one of (I-1) to (I-4), wherein the saponification rate is 20 to 40%, preferably about 30%.
(I-6) The keratinocyte thickening agent according to any one of (I-1) to (I-5), which further contains a liquid saturated glycol.
(I-7) The keratinocyte thickening agent described in (I-6), wherein the content of the liquid saturated glycol is 0.5 to 60% by mass.
(I-8) The liquid saturated glycol is at least one selected from the group consisting of propylene glycol, dipropylene glycol, 1,3-butylene glycol, and polyethylene glycol, (I-6) or (I-7) A keratinocyte thickening agent according to any one of the above.
(I-9) The keratinocyte thickening agent according to any one of (I-1) to (I-8), which is an O / W emulsion composition.
(I-10) The keratinocyte thickening agent according to any one of (I-1) to (I-9), which is an external preparation for skin.

  In the above, “keratinocyte thickening agent” can also be referred to as “skin softener”.

(II) Method for producing keratinocyte thickening agent (II-1) Using at least a higher fatty acid, an alkali, and a higher alcohol as raw materials, and a step of mixing them and a step of standing (I-1) A method for producing a keratinocyte thickening agent according to any one of to (I-10).
(II-2) The compounding amount of higher fatty acid is 8-30% by mass, the compounding amount of alkali is 0.2-5% by mass, and the content of higher alcohol is 0.5-8% by mass, (II- 1) The manufacturing method as described.
(II-3) The production method as described in (II-1) or (II-2), wherein the amount of the alkali is 4 to 8 parts by mass with respect to 100 parts by mass of the higher fatty acid.
(II-4) The higher fatty acid and the higher fatty acid of the higher fatty acid salt are the same or different, and are saturated or unsaturated fatty acids having 14 to 18 carbon atoms. (II-1) to (II-3) The manufacturing method described in any one.
(II-5) The production method according to any one of (II-1) to (II-4), wherein the higher alcohol is a saturated or unsaturated monohydric alcohol having 14 to 18 carbon atoms.
(II-6) The production method according to any one of (II-1) to (II-5), which is a method for producing a keratinocyte thickening agent having a saponification rate of 20 to 40%, preferably about 30%.
(II-7) The production method according to any one of (II-1) to (II-6), further comprising a step of blending a liquid saturated glycol.
(II-8) The production method according to (II-7), wherein the blending amount of the liquid saturated glycol is 0.5 to 60% by mass.
(II-9) The liquid saturated glycol is at least one selected from the group consisting of propylene glycol, dipropylene glycol, 1,3-butylene glycol, and polyethylene glycol, (II-7) or (II-8) The manufacturing method described in any one of.
(II-10) The keratinocyte thickening agent is an O / W type emulsion composition, and preferably has a step of mixing at 70 to 90 ° C., any of (II-1) to (II-9) Manufacturing method to be described.
(II-11) The standing step is a step of leaving the mixture (emulsion) of the higher fatty acid, alkali, and higher alcohol obtained in the mixing step at 5 to 40 ° C. (II- 1) The production method according to any one of (II-11).
(II-12) The production method according to any one of (II-1) to (II-11), wherein the keratinocyte thickening agent is an external preparation for skin, and has a step of preparing the form for external use.

  Similarly to the above, “keratinocyte thickening agent” can also be referred to as “skin softener”.

  In the production method of the present invention, the raw materials such as the higher fatty acid, alkali, and higher alcohol are prepared by mixing together a composition containing a higher fatty acid and a higher alcohol and a composition in which an alkali is dissolved in a solvent. Emulsified. For this reason, in the above, a mixing process can also be paraphrased as an emulsification process.

(III) A cosmetic method for thickening keratinocytes and increasing skin flexibility (III-1) A keratinocyte thickening agent described in any one of (I-1) to (I-10) above is applied to the skin of a subject. A cosmetic method comprising thickening keratinocytes to increase skin flexibility, comprising a step of applying.
(III-2) The cosmetic method according to (III-1), wherein the cosmetic method is a method for improving skin symptoms caused by aging.
(III-3) (III-1) or (III-2), wherein the cosmetic method is a cosmetic method for improving at least one skin symptom selected from the group consisting of age-induced skin hardening and dryness. Beauty method described in.

  According to the keratinocyte thickening agent of the present invention, it is applied to skin having symptoms such as aging, which causes the skin to become hard or dry, thereby improving these symptoms and softening the skin. , Can give a plump feeling. Specifically, the keratinocyte thickening agent of the present invention easily penetrates into keratinocytes, and increases the amount of components in the keratinocytes (for example, the amount of bound keratin water), thereby increasing the thickness of keratinocytes. Thus, the flexibility of the skin can be increased, and a fluffy feeling can be imparted to the skin.

(I) Keratinocyte thickener The keratinocyte thickener of the present invention is characterized by containing a higher fatty acid, a higher fatty acid salt, and a higher alcohol. In addition, “keratinocyte thickening agent” can be restated as “skin softener”.

(A) Higher fatty acid In the present invention, the higher fatty acid is not limited, but is preferably a saturated or unsaturated fatty acid having 14 to 18 carbon atoms. Such fatty acids include myristic acid (14: 0), pentadecylic acid (15: 0), palmitic acid (16: 0), palmitoleic acid (16: 1), margaric acid (17: 0), stearic acid (18: 0), oleic acid (18: 1), vaccenic acid (18: 1), linoleic acid (18: 2), linolenic acid (18: 3), and eleostearic acid (18: 3) . The numbers in parentheses after the chemical names indicate the number of carbon atoms of the fatty acid and the latter the number of double bonds. From the viewpoint of good use feeling in addition to the keratinocyte thickening action, saturated fatty acids having 16 to 18 carbon atoms are more preferable, and palmitic acid, stearic acid, and margaric acid are particularly preferable.

  Although the content rate of these higher fatty acids in the keratinocyte thickening agent of this invention is not restrict | limited, Usually, it is about 5-25 mass%. Preferably it is 7-20 mass%, More preferably, it is 7-11 mass%.

(B) Higher fatty acid salt As described later, higher fatty acid salt is produced by alkali reacting with higher fatty acid used as a raw material in the production process. It may be present and its origin is not particularly limited.

  The higher fatty acid constituting the higher fatty acid salt is not limited, but is preferably a saturated or unsaturated fatty acid having 14 to 18 carbon atoms. Such fatty acids include myristic acid (14: 0), pentadecylic acid (15: 0), palmitic acid (16: 0), palmitoleic acid (16: 1), margaric acid (17: 0), as in the above higher fatty acids. ), Stearic acid (18: 0), oleic acid (18: 1), vaccenic acid (18: 1), linoleic acid (18: 2), linolenic acid (18: 3), and eleostearic acid (18: 3). From the viewpoint of good use feeling in addition to the keratinocyte thickening action, saturated fatty acids having 16 to 18 carbon atoms are more preferable, and palmitic acid, stearic acid, and margaric acid are particularly preferable.

  Examples of higher fatty acid salts include alkali metal salts (fatty acid sodium, fatty acid potassium, etc.) of the above higher fatty acids, alkaline earth metal salts (eg, fatty acid magnesium, fatty acid calcium, fatty acid barium, etc.), and ammonia salts (fatty acid ammonium). , Higher fatty acids and amines, hydroxylamines, imines, guanidines, amine oxides, alkanolamines, alkoxylated amines, and alkylamines (diethanolamine, triethanolamine, isopropanolamine, diisopropanolamine, Triisopropanolamine, aminobutanol, aminoethylpropanediol, aminomethylpropanol, aminomethylpropanediol, isopropylamine, methylethanolamine, diisopropyl Min, dipropylenetriamine, glucamine, N- methylglucamine, morpholine, tromethamine), cocamine compounds, soyamine acids, oleamine acids, stearamine compounds can be exemplified the reaction product of an organic amine such as Kuoteruniumu class. Preferred are alkali metal salts or alkaline earth metal salts of fatty acids, and more preferred are fatty acid sodium salts or fatty acid potassium which are alkali metal salts of fatty acids.

  Although the content rate of these higher fatty acid salts in the keratinocyte thickener of this invention is not restrict | limited, Usually, it is about 2-10 mass%. Preferably it is 2-9 mass%, More preferably, it is 3-9 mass%.

(C) Higher alcohol In the present invention, the higher alcohol is not limited, but is preferably a saturated or unsaturated monovalent alcohol having 14 to 18 carbon atoms. Such higher alcohols include myristyl alcohol, pentadecyl alcohol, cetanol, cetosallyl alcohol, palmitoleyl alcohol, 1-heptadecanol, stearyl alcohol, isostearyl alcohol, elaidyl alcohol, oleyl alcohol, linoleyl alcohol, and lisinoleyl. Mention may be made of fatty alcohols such as alcohols or synthetic alcohols. From the viewpoint of good usability in addition to the keratinocyte thickening action, it is preferably a saturated monohydric alcohol having 16 to 18 carbon atoms, particularly preferably cetanol, cetosallyl alcohol, palmitoleyl alcohol, 1-hepta. Decanol, stearyl alcohol, isostearyl alcohol, oleyl alcohol.

  Although the content rate of these higher alcohols in the keratinocyte thickening agent of this invention is not restrict | limited, Usually, it is about 0.5-8 mass%. Preferably it is 1-8 mass%, More preferably, it is 1-3 mass%.

(D) Liquid saturated glycol The keratinocyte thickening agent of the present invention may contain liquid saturated glycol. The liquid saturated glycol acts as a moisturizer or softener on the skin. Examples of such liquid saturated glycol include, but are not limited to, at least one selected from the group consisting of propylene glycol, dipropylene glycol, 1,3-butylene glycol, and polyethylene glycol. Preferred are propylene glycol, dipropylene glycol and polyethylene glycol, and more preferred are propylene glycol and polyethylene glycol. Although it does not restrict | limit, the range of 0.5-60 mass% can be mentioned as a content rate of the liquid saturated glycol in the keratinocyte thickening agent of this invention. Preferably 1-60 mass%, More preferably, 5-60 mass% can be mentioned.

(E) Other components The keratinocyte thickening agent of the present invention is limited to the above (A) to (C) as long as it does not hinder the effect of the present invention to increase the thickness of the keratinocytes and enhance the flexibility of the skin. In addition to the components or the components (A) to (D), other components may be contained. Examples of such components include humectants, thickeners, surfactants, oily components, antioxidants, antiseptic / bactericides, powder components, fragrances, pigments, water, and the like.

  Examples of humectants include, but are not limited to, glycerin; saccharides such as sorbitol, xylitol, and trehalose; sodium pyrrolidonecarboxylate, lactic acid bacteria fermented rice, hyaluronic acid and its derivatives (for example, hyaluronic acid having a molecular weight of several thousand to several million or its Salts, acetylated hyaluronic acid, propylene glycol hyaluronate, hydroxypropyltrimonium hyaluronate), mucopolysaccharides (eg chondroitin and its derivatives, heparin and its derivatives), elastin and its derivatives, collagen and its derivatives, hydrolysis Silk protein, lactic acid, urea, higher fatty acid octyldodecyl, phytosterol, soybean phospholipid, cholesteryl isostearate, seaweed extract, collagen derived from seafood and its derivatives, various amino acids and their Et derivatives (such as trimethyl glycine, etc.), luffa extract, Byakkyuu extract, soybean milk fermented liquor, natto extract, and the like rice-derived extract and fermented product.

  Thickeners are not limited, but include, for example, components derived from brown algae, green algae, or red algae such as alginic acid, agar, carrageenan, and fucoidan; polysaccharides such as beech extract, pectin, locust bean gum, aloe polysaccharide; xanthan gum, tragacanth gum Gums such as guar gum; cellulose derivatives such as carboxymethyl cellulose and hydroxyethyl cellulose; synthetic polymers such as polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer, acrylic acid / methacrylic acid copolymer; polyglutamic acid and its derivatives; glucosyl trehalose And sugar compounds mainly composed of hydrolyzed hydrogenated starch.

  The surfactant is not limited, but for example, polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene cured Nonionic surfactants such as castor oil and polyoxyethylene sorbitol fatty acid ester; fatty acid salt, alkyl sulfate, alkylbenzene sulfonate, polyoxyethylene alkyl ether sulfate, polyoxyethylene fatty amine sulfate, polyoxyethylene alkylphenyl Ether sulfate, polyoxyethylene alkyl ether phosphate, α-sulfonated fatty acid alkyl ester salt, polyoxyethylene alkyl phenyl ether Anionic surfactants such as ruphosphates; quaternary ammonium salts, primary to tertiary aliphatic amine salts, trialkylbenzylammonium salts, alkylpyridinium salts, 2-alkyl-1-alkyl-1-hydroxyethyls Cationic surfactants such as imidazolinium salt, N, N-dialkylmorphonium salt, polyethylene polyamine fatty acid amide salt; N, N-dimethyl-N-alkyl-N-carboxymethylammoniobetaine, N, N, N And amphoteric surfactants such as -trialkyl-N-alkyleneammoniocarboxybetaine and N-acylamidopropyl-N ', N'-dimethyl-N'-β-hydroxypropylammoniosulfobetaine. In addition, stevia derivatives such as enzyme-treated stevia, lecithin and its derivatives, lactic acid bacteria fermented rice, lactic acid bacteria fermented germinated rice, lactic acid bacteria fermented cereals (wheat, beans, millet, etc.), beech extract etc. You can also

  Examples of the oil component include, but are not limited to, hydrocarbons such as liquid paraffin, petrolatum, paraffin wax, and squalane.

  Antioxidants include, but are not limited to, for example, butylhydroxyanisole, butylhydroxytoluene, propyl gallate, vitamin E and its derivatives, vitamin C (ascorbic acid) and its derivatives, ubidecaquinone (ubiquinone), rutin, rutin glucoside, white Examples of the extract include a coconut extract, a rice extract, a purple extract, a birch extract, a hamamelis extract, a oolong tea extract, a black bean hydrolyzed extract, a peony extract, a beech cucumber extract, and a sorghum extract.

  Examples of the antiseptic / bactericidal agent include, but are not limited to, paraoxybenzoates such as urea, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate, phenoxyethanol, dichlorophene, hexachlorophene, hydrochloric acid Examples include chlorhexidine, benzalkonium chloride, salicylic acid, ethanol, undecylenic acid, phenols, jamal (imidazolidene urea), dry bark, propolis extract, and methylisothiazolinone.

  Examples of powder components include, but are not limited to, sericite, titanium oxide, talc, kaolin, bentonite, zinc oxide, magnesium carbonate, magnesium oxide, zirconium oxide, barium sulfate, silicic anhydride, mica, 6- or 12-nylon. There are powder, polyethylene powder, silk powder, cellulosic powder, powder of cereals (rice, wheat, corn, millet, etc.), powder of beans (soybean, red beans, etc.).

  Further, if necessary, other physiologically active ingredients (fibroblast activator, whitening agent, skin aging prevention / roughness improving agent, etc.) may be blended within a range not impeding the effects of the present invention.

  The fibroblast activator is not limited, but for example, bilberry leaf extract, polyamine, aloe extract, cuckoo extract, chlorella extract, placenta extract, sugar maple tree sap, royal jelly, yeast extract, mucopolysaccharide fluid, dairy extract, soybean extract, Whey etc. can be mentioned.

  Examples of the whitening agent include, but are not limited to, t-cycloamino acid derivatives, kojic acid and its derivatives, vitamin C (ascorbic acid) and its derivatives, hydroquinone or its derivatives, ellagic acid and its derivatives, nicotinic acid and its derivatives, resorcinol Derivatives, tranexamic acid and derivatives thereof, 4-methoxysalicylic acid potassium salt, magnolignan (5,5'-dipropyl-biphenyl-2,2'-diol), 4-HPB (rhodenol, 4- (4-hydroxyphenyl)- 4-butanol)), hydroxybenzoic acid and its derivatives, vitamin E and its derivatives, α-hydroxy acid, AMP (adenosine monophosphate, adenosine monophosphate), placenta extract, suha akuhi extract, yukinoshita extract, rice bran Extract or its hydrolyzate, white coconut extract Or hydrolyzate thereof, fermented white coconut, peony extract or hydrolyzate thereof, lactic acid bacteria fermented rice, lactic acid bacteria fermented rice, lactic acid bacteria fermented cereals (wheat, legumes, millet), murasakixikibu extract, lotus seed extract Or hydrolyzate thereof, fermented lotus seed, extract of party ginseng, pearl hydrolyzate, fermented pearl seed, fermented royal jelly, fermented sake lees, Pandanus amaryllifolius Roxb. Examples thereof include an extract of a sea flava (Arcangelicia flava Merrilli) and a chamomile extract.

  The skin aging prevention / roughness improving component is not limited, for example, coral grass extract, rice leaf extract or hydrolyzate thereof, eggplant (water eggplant, long eggplant, Kamo eggplant, rice eggplant etc.) extract or Hydrolyzate thereof, extract of seaweed such as catamen giraffe, extract of marine flowering plant such as sea eel, jellyfish water, rice extract or hydrolyzate thereof, rice fermentation extract, germinated rice extract or hydrolyzate thereof Germinated rice fermented product, black bean extract or hydrolyzate thereof, collagen derived from animal or fish and derivatives thereof, elastin and derivatives thereof, intercellular lipids such as ceramide, glycyrrhizic acid and derivatives thereof (dipotassium salt, etc.), t- Cycloamino acid derivative, vitamin A and its derivative, t-cycloamino acid derivative, vitamin A and its derivative, vitamin E and its derivative (d, l-α-toco Sodium eryl phosphate), allantoin, α-hydroxy acids, diisopropylamine dichloroacetate, γ-amino-β-hydroxybutyric acid, coenzyme Q-10, α-lipoic acid, ergothioneine, allantoin, diisopropylamine dichloroacetate, γ-amino- β-hydroxybutyric acid, gentian extract, licorice extract, carrot extract, aloe extract, beetle extract, anaosa extract, zizyphus joazeiro extract, beech extract, beetle aloe extract, mannenrou extract, ginkgo biloba Extract, Horsetail extract, Safflower extract, Panax ginseng extract, Horseshoe extract, Jasmine extract, Astragalus extract, Mango extract, Cherimoya extract, Mangosteen extract, Tabebuia impetigenosa Extracts, yeast extract, eggshell membrane extract protein, deoxyribonucleic acid potassium salt, lotus seed fermented liquid, pollen cargo extract and the like can be mentioned.

  As will be described later, the keratinocyte thickening agent of the present invention is produced using higher fatty acids and alkalis as raw materials, and as a result, contains a part of higher fatty acids in a saponified state. The saponification rate of the keratinocyte thickening agent of the present invention is not limited, but can be in the range of 20 to 40%. Preferably it is 20 to 35%, more preferably 25 to 35%, particularly preferably about 30%.

  The keratinocyte thickening agent of the present invention comprises the above-mentioned components (A) to (C) and, if necessary, the (D) component and / or the (E) component, and a desired shape (solid, Semi-solid [gel, cream, ointment, etc.] and liquid [emulsion, lotion, etc.]). An emulsion, particularly an O / W emulsion, is preferred, and a creamy external composition can be more preferably prepared. The external composition may be included in any category of pharmaceuticals, quasi drugs, and cosmetics. Preferred are quasi-drugs for external use and cosmetics, and more preferred are cosmetics.

  Although it does not restrict | limit as a form as a pharmaceutical for external use or a quasi-drug, For example, a cream, an ointment, a plaster, a poultice, a lotion, an emulsion, a liquid, an aerosol, etc. can be mentioned. Creams and emulsions are preferred. Although it does not restrict | limit as a form as cosmetics, For example, as a skin care cosmetics, a lotion, a cosmetic liquid, a pack, a massage cream, an emulsion, a moisture cream, a vanishing cream, a cleansing cream, a lip balm etc. can be mentioned. Massage cream, milky lotion, moisture cream, burnishing cream and cleansing cream are preferred.

(II) Method for producing keratinocyte thickener The keratinocyte thickener of the present invention containing at least the components (A) to (C) described above uses at least a higher fatty acid, an alkali, and a higher alcohol as raw materials. It can prepare through the process of mixing these, and the process of leaving still.

  The kind of higher fatty acid and higher alcohol used here is as described in the above (I), and the above description can be used.

  As the amount of the higher fatty acid used for the production, as described above, the proportion of the higher fatty acid contained in the keratinocyte thickening agent after preparation is usually about 5 to 25% by mass, preferably 7 to 20% by mass. Preferably, it is 7 to 11% by mass, and the saponification rate in that case is 20 to 40%, preferably 20 to 35%, more preferably 25 to 35%, and as long as it is particularly limited. It is not limited. When the total amount of production raw materials is 100% by mass, the proportion of higher fatty acids to be used is usually 8 to 30% by mass. Preferably it is 10-30 mass%, More preferably, it is 10-15 mass%.

  The amount of higher alcohol used in the production is not limited, but when the total amount of raw materials for production is 100% by mass, as described in (I), usually mention about 0.5 to 8% by mass. Can do. Preferably it is 1-8 mass%, More preferably, it is 1-3 mass%.

  The alkali used for the production is a substance that exhibits a pH of 7 or more when it is made into an aqueous solution, and is a substance that reacts with the higher fatty acid to produce the above-mentioned higher fatty acid salt as a saponified product.

  The alkali includes both inorganic alkalis and organic alkalis. Examples of the inorganic alkali include alkali metal or alkaline earth metal hydroxide salts (for example, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, etc.), alkali metal carbonates or bicarbonates ( For example, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate), alkali metal phosphates (eg, sodium phosphate, potassium phosphate), ammonia inorganic salts (eg, ammonium hydroxide, ammonium phosphate, carbonic acid) Or ammonium bicarbonate). Examples of the organic alkali include amines, hydroxylamines, imines, guanidines, amine oxides, alkanolamines, alkoxylated amines, and alkylamines (diethanolamine, triethanolamine, isopropanolamine, diisopropanolamine). , Triisopropanolamine, aminobutanol, aminoethylpropanediol, aminomethylpropanol, aminomethylpropanediol, isopropylamine, methylethanolamine, diisopropylamine, dipropylenetriamine, glucamine, N-methylglucamine, morpholine, tromethamine), Examples include cocamines, soiamines, oleamines, stearamines, quaterniums and the like. An inorganic alkali is preferable. More preferred are alkali metal or alkaline earth metal hydroxide salts, alkali metal carbonates, bicarbonates, or phosphates, with alkali metal hydroxide salts being particularly preferred.

  Although it does not restrict | limit as an amount of the alkali used for manufacture, When the total amount of a manufacturing raw material is 100 mass%, about 0.5-5 mass% can be mentioned normally. Preferably it is 0.5-2 mass%, More preferably, it is 0.6-2 mass%.

  Further, the ratio of the alkali to 100 parts by mass of the higher fatty acid used as a production raw material is not limited, but the saponification rate is 20 to 40%, preferably 20 to 35%, more preferably 25 to 35%. Although it is not limited as long as it is limited, specifically, for example, 0.5 to 5 parts by mass, preferably 0.5 to 2 parts by mass, and more preferably 0.6 to 2 parts by mass. be able to.

  Further, when the keratinocyte thickening agent of the present invention contains liquid saturated glycol and / or other optional components as other components, the keratinocyte thickening agent of the present invention contains liquid saturated glycol and / or other components in addition to the above components. It is manufactured by blending optional components. The kind of liquid saturated glycol is as above-mentioned, The quantity can mention about 0.5-60 mass% normally, when the total amount of a manufacturing raw material is 100 mass%. Preferably it is 1-60 mass%, More preferably, it is 5-60 mass%.

  The production method of the present invention basically includes a step of blending and mixing these components as raw materials as described above. Mixing is the shape of the keratinocyte thickening agent to be manufactured (solid, liquid, semi-solid), formulation (cream, ointment, plaster, lotion, emulsion, liquid, aerosol), administration route (internal use, external use) In addition, depending on its use (pharmaceuticals, quasi-drugs, and cosmetics), it can be carried out according to the usual method. Since the preferred embodiment of the keratinocyte thickening agent of the present invention is an emulsion, more preferably a cream, particularly an O / W cream external preparation for skin, preferably an emulsion, more preferably a cream, especially O. According to the manufacturing method of / W type cream, it can prepare through the emulsification process by mixing.

  The mixing step (emulsification step) can be carried out according to a conventional method such as heating the raw material to a predetermined temperature and then stirring and emulsifying under a predetermined condition using a mixer such as a homogenizer, a homomixer, or a stirrer. . More specifically, a mixture of a higher fatty acid and a higher alcohol that has been heated and dissolved in advance, and an alkali that has also been previously heated and dissolved in a solvent, for example, using the above-mentioned mixer A method of stirring and mixing can be mentioned, and thus a keratinocyte thickening agent having a desired emulsion form can be prepared. Although not limited, such a mixing step is preferably performed in a heated state. Although the temperature in particular is not restrict | limited, Preferably it is 60-90 degreeC, Preferably it is 70-90 degreeC, More preferably, 75-85 degreeC can be illustrated. The emulsion thus obtained can then be cooled (preferably about 30 to 35 ° C. or less) to prepare an emulsion composition in which emulsification is stable.

  The keratinocyte thickening agent of the present invention is subjected to a standing step after emulsification preparation. The standing step is an important step in obtaining the keratinous thickening action and the feeling of soft and plump skin in the emulsion composition prepared above. Such a standing step may be performed under the condition that the above-described effects and actual feelings can be obtained, but can be usually performed by standing at a temperature of 5 to 40 ° C. Preferably, it is allowed to stand under a temperature condition of 10 to 30 ° C. Although it does not restrict | limit the period to leave still, Preferably it is 5-28 days, More preferably, it is 7-21 days.

(III) Cosmetic method The present invention applies the above-mentioned keratinocyte thickening agent of the present invention to a subject whose skin flexibility has decreased due to aging or the like, thereby increasing the keratinocyte thickness of the subject's skin. The present invention relates to a cosmetic method that increases skin flexibility and provides a plump feeling. Note that the method targeted by the present invention is a cosmetic method, not a treatment method for humans.

  For example, a subject whose amount of water, NMF, etc. in the keratinocytes has decreased due to aging or the like has a skin deterioration symptom in which the skin is soft and dry, such as skin is hard and dry, and there is no plump feeling. have.

  The subject is not particularly limited, but is preferably a person having the above-mentioned skin deterioration symptoms due to aging. In general, if both men and women are over 30 years old, there is a possibility of becoming the subject. Preferably it is 40 years old or more, More preferably, it is 45 years old or more, More preferably, it is 50 years old or more.

  The keratinocyte thickening agent of the present invention varies depending on its form, but when it has a form such as a plaster, ointment, cream, liniment, lotion, milky lotion, liquid, aerosol, etc., the pharmaceutical preparation for external use, quasi-drug and cosmetics Can be used by applying or spraying to the skin of the desired site of the subject. Moreover, when external medicine, a quasi-drug, and cosmetics have the form of a poultice, it can be used by sticking the external medicine, a quasi-drug, and a cosmetic to the skin of a desired part of a subject. Application to the skin may be performed once or a plurality of times a day, and examples thereof include a method of applying in the morning and evening (before going to bed). Thus, it is possible to suppress (prevent) or improve the occurrence of skin deterioration symptoms possessed by subjects whose skin flexibility has decreased due to aging or the like.

  Hereinafter, the present invention will be described based on experimental examples and examples. However, the experimental examples and examples are examples of the present invention, and the present invention is not limited to these experimental examples and examples.

Experimental Example 1 Evaluation of the effect on keratinocyte thickness External composition for skin (cream) comprising the composition shown in Table 2 (Examples 1 to 4), and external composition for skin comprising the composition shown in Table 3 (cream) Comparative Example 1) was applied to human skin to measure the thickness of the keratinocytes, and the keratinocyte thickening action of each external composition for skin was evaluated.

(1) Preparation of test sample (external composition for skin) Compositions (Examples 1 to 4) described in Table 2 were prepared as follows.
1. Each component of the A phase described in Table 1 is mixed in the ratio described in the table and heated to 80 ° C.
2. Subsequently, each component of B phase is mixed in the ratio of Table 1, and it heats to 80 degreeC.
3. Next, the mixture of the phase B components is added to the mixture of the phase A components, and the mixture is stirred at 80 ° C.
4). Subsequently, this is stirred while cooling to 30 degreeC (natural cooling), and the emulsion composition (cream form) (test sample) which consists of a composition of Table 2 is prepared.
5). Each prepared emulsified composition is allowed to stand for 20 days in the dark at 25 ° C. and stored.

  In addition, all the compounding quantities of Tables 1 and 2 mean mass%.

On the other hand, in Comparative Example 1, each component described in Table 3 was mixed in the blending amount (mass%) to prepare a creamy (W / O cream) test sample (external composition for skin). Specifically, it was prepared according to the following method. In Table 3, “PCA-Na” is “dl-pyrrolidonecarboxylate sodium solution”.
Moreover, the process of 3-6 of the following method was performed on 75 degreeC conditions.

1. Each component belonging to A described in Table 3 is weighed and mixed with stirring at 75 ° C. (composition A).
2. Similarly, the components belonging to B, C and D described in Table 3 are weighed and mixed at 75 ° C. with stirring (compositions B to D).
3. When the composition A becomes uniform, the composition B is added little by little to emulsify (composition AB).
4). To the composition AB thus prepared, the composition C is added with stirring to prepare the composition ABC.
5). While stirring composition ABC thus prepared, composition D is added to prepare composition ABCD.
6). This is homogenized with a homomixer.
7). While stirring, cool to 35 ° C.
8). The prepared emulsified composition is allowed to stand for 20 days in the dark at 25 ° C. and stored.

  The preparations of Examples 1 to 4 and Comparative Example 1 were all performed in a room temperature environment except for the matters described.

(2) Experimental method According to the following procedure, a test sample (Examples 1 to 4 and Comparative Example 1) was applied to the inner side of the human forearm (test site), and the thickness of the keratinocytes at the skin test site was measured before and after application. The thickening effect on the keratinocytes of the test sample was evaluated.

(2-1) Application method (i) The inside of the forearm (test site) of a human (n = 3) is exposed to the laboratory environment (room temperature 22 ° C., relative humidity 64%) for 20 minutes to acclimatize to the indoor environment.
(Ii) A test sample is applied at a ratio of 10 mg to the 2 cm × 2 cm image inside the forearm. Apply by lightly rubbing 3-4 times with your finger to adjust to the skin. Allow to stand for 30 minutes in an indoor environment (room temperature).
(Iii) Lightly hold the test site with a tissue (tissue off) so that there is no test sample (cream) remaining on the skin surface, and use for measurement.

(2-2) Measurement method The thickness of the keratinocytes at the test site is measured before and after application of the test sample under conditions of room temperature 22 ° C and relative humidity 64% in vivo confocal Raman spectroscope (Model 3510, RiverD International BV). ) (Measurement wavelength 671 nm, output 15.1 mW). Specifically, place the test site on the measurement stage, irradiate the test site with laser light from an in vivo confocal Raman spectrometer, measure the corneal depth (μm) distribution of water content, Calculated. The keratinocyte thickness (μm) is the water content value (mass%) (vertical axis) with respect to the skin depth (2-30 μm) (horizontal axis) measured with an in vivo confocal Raman spectroscope, every 2 μm skin depth. The inflection point can be obtained by plotting as shown in FIG. 3 and FIG. 4 of Non-Patent Document 3, and the skin depth (μm) at the inflection point can be obtained.

(3) Determination method The measured value (keratin cell thickness) before application of each test sample and the measured value (keratin cell thickness) after application are statistically processed to determine whether there is a significant difference at a significance level of 5% ( Student-t test.

(4) Experimental results The results are shown in Tables 2 and 3.

  The case where the measured value after application had a significant difference with respect to the value before the measurement was marked with ◯, and the case where there was no significant difference was marked with x.

  As shown in Tables 2 and 3, the W / O type cream of Comparative Example 1, which was expected to increase the keratinocyte thickness, showed no change in the keratinocyte thickness before and after its application. It was recognized that the keratinocyte thickness of the composition for external use of skin (Examples 1 to 4) significantly increased by its application. In this experiment, there is no change in the number of stratum corneum, and the amount of water contained in the stratum corneum is used as an index. It has been found that the thickness of the horny layer increases, that is, the amount of water held in the horny layer (keratinocytes) increases, and the thickness of each keratinocyte increases.

Experimental Example 2 Evaluation of Effect on Skin Flexibility 0.5 g of the composition for external use of skin of Example 1 and Comparative Example 1 prepared in Experimental Example 1 was applied to the face of a cosmetic evaluation panel (n = 10) and applied. After 30 minutes, the skin softness and plumpness were evaluated in five levels according to the following indicators.

[index]
5: Good 4: Slightly good 3: Neither of them 2: Slightly bad 1: Bad

  The evaluation points of each panel were summed up and judged from the total value as follows.

◯: 90 points or more Δ: 80 points or more and less than 90 points ×: less than 80 points As a result, Example 1 was ○, and Comparative Example 1 was ×.

Formulation Example An external skin composition (cream) having the composition described in Table 4 was prepared as a keratinocyte thickening agent. Specifically, first, the components of the phase A described in Table 4 are taken at the ratio shown in Table 4 and heated to 80 ° C. Next, the components of phase B are taken at the ratios shown in Table 4 and heated to 80 ° C. Next, the mixture of the phase B components is added to the mixture of the phase A components and stirred at 80 ° C. Next, this was stirred while being cooled to 30 ° C. (natural cooling) to prepare an emulsified composition (cream) having the composition shown in Table 5. Next, as a standing step, Formulation Example 1 was allowed to stand at 10 ° C. for 30 days, Formulation Example 8 was allowed to stand at 30 ° C. for 5 days, and the other formulation examples were allowed to stand at 20 ° C. for 25 days.

Claims (6)

  A keratinocyte thickening agent containing a higher fatty acid, a higher fatty acid salt, and a higher alcohol.   The keratinocyte thickening according to claim 1, wherein the content of the higher fatty acid is 5 to 25% by mass, the content of the higher fatty acid salt is 2 to 10% by mass, and the content of the higher alcohol is 0.5 to 8% by mass. Agent.   The keratinocyte thickening agent according to claim 1 or 2, wherein the higher fatty acid and the higher fatty acid of the higher fatty acid salt are the same or different and are saturated or unsaturated fatty acids having 14 to 18 carbon atoms.   The keratinocyte thickening agent according to any one of claims 1 to 3, wherein the higher alcohol is a saturated or unsaturated monohydric alcohol having 14 to 18 carbon atoms.   The keratinocyte thickening agent according to any one of claims 1 to 4, wherein the saponification rate is 20 to 40%.   The manufacturing method of the keratinocyte thickening agent in any one of Claims 1-5 which has the process of mixing these using a higher fatty acid, an alkali, and a higher alcohol as a raw material, and the process of leaving still.