JP2017019754A - Elastase inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an elastase inhibitor that has high elastase inhibitory effect.SOLUTION: An elastase inhibitor comprises ginger extract and acetyl hexapeptide.SELECTED DRAWING: None

Description

  The present invention relates to an elastase inhibitor.

One of the effects that can be obtained by applying cosmetics to the skin is to suppress skin aging. Regarding the causes of skin aging, the effects of aging, drying, oxidation, sunlight (ultraviolet rays) and the like are cited as main factors. Skin aging is recognized by a decrease in collagen and elastin in the skin dermis, a decrease in mucopolysaccharides such as hyaluronic acid, and cell damage by ultraviolet rays.
Among them, elastin cross-links each other and contributes to the elasticity of the tissue, but elastin is denatured and destroyed by overexpression of elastin, which is an elastin-degrading enzyme, due to UV exposure and aging. It is thought to lead to a decline in sex. Therefore, suppressing the activity of elastase is important in terms of giving skin elasticity and elasticity and preventing skin aging.

  Patent Document 1 (Japanese Patent Application Laid-Open No. 9-87136) discloses blending an extract of P. niruri L. belonging to the genus Phyllanthuss of the Euphorbiaceae family into a skin external preparation, and such It describes that an external preparation for skin can be used as an elastase inhibitor.

  Patent Document 2 (Japanese Patent Application Laid-Open No. 2000-119189) effectively uses a plant selected from shrimp, hydrolyzed almonds, walnut mushrooms, clove, ages, hawthorn and birch, or an extract, steam distillate, and pressed product. Techniques relating to elastase inhibitors as ingredients are described.

JP-A-9-87136 JP 2000-119189 A

  However, due to the recent increase in consumer health and beauty awareness, skin cosmetics having a better anti-aging effect against aging have been demanded. In this regard, the techniques described in Patent Documents 1 and 2 still have room for improvement in terms of providing a more excellent elastase inhibitor.

  The present inventors have found that an elastase inhibitory activity including a ginger extract and an acetyl hexapeptide can provide excellent elastase inhibitory activity.

  The present invention provides an elastase inhibitor comprising a pepper extract and an acetyl hexapeptide.

  Moreover, this invention provides the skin cosmetics containing the elastase inhibitor in this invention mentioned above.

  According to the present invention, an elastase inhibitor having an excellent elastase inhibitory effect can be obtained.

The elastase inhibitor in this embodiment is a composition containing a Tokyo extract and an acetyl hexapeptide.
Hereinafter, each component will be described with specific examples. Each component can be used alone or in combination of two or more.

The ginger used in the elastase inhibitor of the present embodiment is a rhizome of Zingiber officinale Roscoe.
The pepper extract is obtained from one or two or more sites (hereinafter referred to as “original”) selected from the whole plant of each plant or its leaves, flowers, bark, roots, branches and the like. Specifically, after the raw material is dried or pulverized without drying, it is extracted with a solvent at room temperature or under heating, or extracted with an extractor such as a Soxhlet extractor to extract the ginger extract. Can be obtained.

Here, the solvent used for extraction is not limited, for example, water; monohydric alcohols such as methanol, ethanol and propanol; polyhydric alcohols such as propylene glycol, 1,3-butylene glycol and glycerin; ethyl acetate and the like Liquid fatty acid lower alkyl esters of organic solvents other than those described above, such as hexane, ethyl ether, acetone, etc .; castor oil, liquid paraffin, soybean oil, isopropyl myristate, lower fatty acid triglycerides, sunflower oil, neopentyl glycol dicaprate, squalane By extracting with an oil such as tris [2- (2-ethoxyethoxy) ethyl] phosphate, a pepper extract can be obtained. One or more of these solvents can be used.
As the extraction solvent, one or more selected from the group consisting of polyhydric alcohols such as 1,3-butylene glycol and glycerin, water, ethanol and squalane are preferably used.

  As a specific example of a preferable method for extracting from the active ingredient, there is a method of cutting and pulverizing a dried active ingredient, and using one or more selected from polyhydric alcohol, water, ethanol, and squalane as a solvent. Can be mentioned.

  The obtained ginger extract may be used as it is, but it may be further subjected to dilution, concentration, filtration or the like if necessary.

  The content of the ginger extract in the elastase inhibitor in this embodiment is preferably 0.00001 to 5 mass in terms of evaporation residue with respect to the entire elastase inhibitor from the viewpoint of stably obtaining excellent elastase inhibitory activity. % (Hereinafter also simply referred to as “%”), and 0.0001 to 1% by mass is more preferable from the viewpoint of improving the elastase inhibitory activity effect.

The elastase inhibitor in the present embodiment includes acetylhexapeptide together with the ginger extract. Specifically, acetyl hexapeptide is a kind of synthetic hexapeptide, which is known as a peptide that acts on muscle contraction, and is acetylhexapeptide-8 having the following amino acid sequence shown in Sequence 1.
Ac-Glu-Glu-Met-Gln-Arg-Arg-NH ₂
Ac: Acetyl group Glu: L-α-glutamyl group Met: L-methionyl group Gln: L-glutaminyl group Arg: L-arginyl group

  The present inventors have surprisingly found that elastase inhibitory activity can be improved by combining a yeast extract having an elastase inhibitory effect with an acetylhexapeptide which has no elastase inhibitory effect.

  As the acetyl hexapeptide, for example, a commercially available product can be used. A specific example of a commercially available product is Argireline (registered trademark) manufactured by Lipotec and purchased from Centerchem (Norwalk, CT).

  The content of acetyl hexapeptide in the elastase inhibitor in the present embodiment is preferably 0.00001 to 0.5%, more preferably 0.0001 to 0.1%, still more preferably with respect to the entire elastase inhibitor. The content of 0.0005 to 0.01% is preferable from the viewpoint of improving the elastase inhibitory activity.

  In the elastase inhibitor according to the present embodiment, the mass ratio of the content of the yeast extract (evaporation residue) to the content of acetyl hexapeptide (shower extract / acetyl hexapeptide) improves the elastase inhibitory activity effect. From the viewpoint, 0.01 to 2000 is preferable, 0.08 to 500 is more preferable, and 0.2 to 200 is more preferable.

  In the elastase inhibitor of this embodiment, in addition to the above active ingredients, components that are usually blended, for example, purified water, alcohol, chelating agents, various oil agents, surfactants, emulsifiers, thickeners, preservatives, antioxidants Agents, solvents, medicinal ingredients, powders, pigments, fragrances and the like can be blended.

  In this embodiment, the elastase inhibitor excellent in the elastase inhibitory activity can be obtained by using a combination of a yeast extract and an acetyl hexapeptide. In addition, according to this embodiment, for example, it is possible to obtain an elastase inhibitor having excellent elastase inhibitory activity while being excellent in safety.

<Skin cosmetic>
The skin cosmetic in the present embodiment contains the aforementioned elastase inhibitor.
The content of the elastase inhibitor in the skin cosmetic is preferably 0.00002 to 6%, from the viewpoint of improving the elastase inhibitory activity effect and the stickiness at the time of application and after application, and is preferably 0.00011-1. 0.5% is more preferable, and 0.001 to 0.6% is more preferable.
From the same viewpoint, the content of the ginger extract (evaporation residue) in the skin cosmetic is preferably 0.00001 to 5%, more preferably 0.0001 to 1%, and 0.0005 to 0.5. % Is more preferable.
Furthermore, from the same viewpoint, the content of acetyl hexapeptide in the skin cosmetic is preferably 0.00001 to 0.5%, more preferably 0.0001 to 0.1%, and 0.0005 to 0.01%. Is more preferable.

  In the present embodiment, the mass ratio of the content of the ginger extract (evaporation residue) to the content of the acetyl hexapeptide in the skin cosmetic (the ginger extract / acetyl hexapeptide) is a viewpoint that improves the elastase inhibitory activity effect. And from the point which the stickiness at the time of application | coating and after application | coating is suppressed, 0.01-2000 are preferable, 0.08-500 are more preferable, 0.2-200 are more preferable, 10-100 are still more preferable.

  In the skin cosmetic of the present embodiment, in addition to the components described above, components usually blended in the skin cosmetic, such as purified water, alcohol, chelating agents, various oils, surfactants, emulsifiers, thickeners, Preservatives, antioxidants, solvents, medicinal ingredients, powders, pigments, fragrances, elastase inhibitors other than the elastase inhibitors of this embodiment described above, keratinization improvers, UV absorbers, UV protection agents, collagen, moisturizing An agent, an anti-inflammatory agent, an antioxidant and the like can be added. Preferred examples of other components will be described later with specific examples.

  The skin cosmetic of the present embodiment can be used by applying it to the skin, preferably a site other than the scalp, more preferably any of the face, body, limbs and the like.

  Skin cosmetics of this embodiment are skin lotions such as lotions, lotions, emulsions, beauty creams, base cosmetics, sunscreen cosmetics, packs, massage cosmetics, etc .; as external medicines such as creams containing various drugs Among these, lotions and emulsions are preferable, and emulsions are more preferable from the viewpoint of more effectively expressing the elastase inhibitory effect.

  When the skin cosmetic of the present embodiment is an emulsion, it preferably further has an α-gel structure. Since the skin cosmetic has an α-gel structure, it is possible to moisturize the skin by suppressing the transpiration of the skin, and in addition to the elastase inhibitory effect of the elastase inhibitor of the present embodiment, a further excellent aging An inhibitory effect can be obtained.

From the viewpoint of forming an α-gel structure in the skin cosmetic, for example, it is preferable that the skin cosmetic further includes the following components (A) to (E).
(A) An organic compound having two or more hydroxyl groups, an inorganic value of 220 to 450, and an organic value of 300 to 1000,
(B) an organic compound having one hydroxyl group and having an inorganic value of 100 to 200 and an organic value of 280 to 700;
(C) Ceramides,
(D) One or more compounds selected from the group consisting of nonionic surfactants having a polyoxyethylene group of HLB 10 or higher, ionic surfactants and sphingosine salts, and (E) water.

Component (A) is an organic compound having two or more hydroxyl groups, and has an inorganic value of 220 to 450 and an organic value of 300 to 1000. Component (A) is an organic compound having an inorganic value of 220 to 340 and an organic value of 380 to 840 from the viewpoint of forming an α-gel structure in combination with components (B), (C) and (D). An organic compound having an inorganic value of 250 to 340 and an organic value of 380 to 700 is more preferable.
In this specification, the inorganic value and the organic value are respectively an organic conceptual diagram (Akira Fujita, prediction of organic compounds and an organic conceptual diagram, chemistry area Vol. 11, No. 10 (1957), P. 719. The value of the inorganic value and organic value calculated | required based on -725).

  Specific examples of the component (A) include those represented by the following general formula (1).

(In the general formula (1), Z ¹ represents a structure having two or more hydroxyl groups in a glycerin, sorbitan, sorbitol or sucrose residue, Y ¹ represents an ester bond group or an ether bond group, R represents a hydrocarbon group having 14 to 22 carbon atoms, and n represents a number of 1 to 2.

  In the general formula (1), the hydrocarbon group having 14 to 22 carbon atoms represented by R is preferably a linear hydrocarbon group, for example, a linear alkyl group such as a myristyl group, a palmityl group, a stearyl group, or a behenyl group. A palmitoyl group, an oleyl group, and the like.

  Examples of the compound represented by the general formula (1) include glycerin monofatty acid ester, sorbitan monofatty acid ester, sorbitan difatty acid ester, sorbitol monofatty acid ester, sorbitol difatty acid ester, sucrose monofatty acid ester, glycerin monoalkyl ether, and the like. Can be mentioned.

As component (A), from the viewpoint of forming an α-gel structure in combination with components (B), (C) and (D), glycerin monofatty acid ester, glycerin monoalkyl ether, sorbitan monofatty acid ester and sorbitan difatty acid 1 or more types chosen from the group which consists of ester are preferable, and glycerol mono-fatty acid ester or glycerol monoalkyl ether is more preferable.
Among these, glyceryl monofatty acid ester includes glyceryl monopalmitate (inorganic value 260, organic value 380), glyceryl monostearate (inorganic value 260, organic value 420), glyceryl monobehenate (inorganic value 260). And at least one selected from organic values 500).
As the glycerin monoalkyl ether, monocetyl glyceryl ether (inorganic value 220, organic value 380) and monostearyl glyceryl ether (inorganic value 220, organic value 420) are preferable.
The sorbitan monofatty acid ester is preferably at least one selected from sorbitan monostearate (inorganic value 445, organic value 480).
The sorbitan difatty acid ester is preferably sorbitan distearate (inorganic value 340, organic value 840).
In addition, from the same viewpoint, the component (A) is more preferably glyceryl monobehenate or monocetyl glyceryl ether.

  Component (A) can be used alone or in combination of two or more thereof, and from the viewpoint of improving elastase inhibitory activity and moisturizing properties and improving anti-aging effect, the content in skin cosmetics is skin cosmetics. Preferably it is 0.05 mass% or more with respect to the whole, 0.1 mass% or more is more preferable, 0.3 mass% or more is further more preferable, 0.6 mass% or more is further more preferable, and it is easy to extend. From the viewpoint of improving the thickness, it is preferably 10% by mass or less, preferably 6% by mass or less, more preferably 3.5% by mass or less, and further preferably 1.5% by mass or less. The content of the component (A) is preferably 0.05 to 10% by mass, more preferably 0.1 to 6% by mass, and 0.3 to 3.5% by mass with respect to the entire skin cosmetic. Is more preferable, and 0.6 to 1.5% by mass is even more preferable.

The component (B) used in the present embodiment is an organic compound having one hydroxyl group and having an inorganic value of 100 to 200 and an organic value of 280 to 700.
Component (B) is an organic compound having an inorganic value of 100 to 182 and an organic value of 300 to 520 from the viewpoint of forming an α-gel structure in combination with components (A), (C) and (D). Is preferred.
Specific examples of the component (B) include one or more compounds selected from higher alcohols having 12 to 22 carbon atoms and sterols, and from the viewpoint of forming an α-gel, those having 12 to 22 carbon atoms. Higher alcohols are preferred.

  As the higher alcohol, those having 14 to 22 carbon atoms are preferable, and those having 16 to 18 carbon atoms are more preferable. The carbon chain constituting the higher alcohol may be either a straight chain or a branched chain, and a straight chain is preferable. Examples of the higher alcohol include myristyl alcohol (inorganic value 100, organic value 280), cetanol (inorganic value 100, organic value 320), stearyl alcohol (inorganic value 100, organic value 360), behenyl alcohol ( Inorganic value 100, organic value 440), oleyl alcohol (inorganic value 102, organic value 360), and the like.

  Examples of sterols include cholesterol (inorganic value 182 and organic value 520) and phytosterol. Phytosterol is a general term for plant sterols such as β-sitosterol, campesterol, stigmasterol, and brassicasterol, and the composition thereof is not limited.

  Component (B) can be used alone or in combination of two or more thereof, from the viewpoint of improving the anti-aging effect, from the viewpoint of improving the feeling of finger tightness and the skin covered with the cosmetic after application. The content in the skin cosmetic is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, still more preferably 0.3% by mass or more, based on the entire skin cosmetic. Is more preferably 5% by mass or more, and preferably 10% by mass or less, more preferably 6% by mass or less, still more preferably 3.5% by mass or less, from the viewpoint of improving ease of stretching. 5 mass% or less is still more preferable. The content of the component (B) is preferably 0.05 to 10% by mass, more preferably 0.1 to 6% by mass, and 0.3 to 3.5% by mass with respect to the entire skin cosmetic. Is more preferable, and 0.5 to 1.5% by mass is even more preferable.

As the ceramide of component (C) used in the present embodiment, one or more selected from (I) naturally-derived ceramide and (II) pseudo-ceramide are preferable. For example, JP 2013-53146 A The ceramide described in 1 is preferred.
Among these, as a specific example of (I) naturally derived ceramide (hereinafter also referred to as “natural ceramide”), ceramide types 1 to 7 (for example, J. Lipid Res., 24: 759 (1983), FIG. 2). And porcine and human ceramides described in FIG. 4 of J. Lipid. Res., 35: 2069 (1994)). Furthermore, these N-alkyl bodies (for example, N-methyl body) are also included.

  These ceramides can be either natural or non-natural (D (-)) optically active or non-natural (L (+)) optically active. Mixtures may be used. The configuration of the above compound may be a natural configuration, a non-natural configuration other than that, or a mixture thereof. Of these, compounds of CERAMIDE1, CERAMIDE2, CERAMIDE3, CERAMIDE5, CERAMIDE6II (above, INCI, 8th Edition) and those represented by the following formula are preferable.

  These may be any of natural extracts and synthetic products, and commercially available products can be used. Examples of such commercially available ceramides include Ceramide I, Ceramide III, Ceramide IIIA, Ceramide IIIB, Ceramide IIIC, Ceramide VI (above, manufactured by Cosmo Farm), Ceramide TIC-001 (manufactured by Takasago Fragrance Co., Ltd.), CERAMIDE II (manufactured by Quest International), DS-Ceramide VI, DS-CLA-Phytoceramide, Phytoceramide, DS-ceramide Y3S (manufactured by DOOSAN), and CERAMIDE2 (manufactured by Sederma).

(II) As pseudo-ceramide, N- (hexadecyloxyhydroxypropyl) -N-hydroxyethylhexadecanamide, N- (hexadecyloxyhydroxypropyl) -N-hydroxyethyldecanamim represented by the following formula: N- (hexadecyloxyhydroxypropyl) -N-hydroxyethylhexadecanamide is preferable.

  Component (C) can be used alone or in combination of two or more thereof, from the viewpoint of improving the anti-aging effect and from the viewpoint of improving the feeling of finger tightness and the feeling that the skin after application is covered with cosmetics. The content in the skin cosmetic is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, still more preferably 0.5% by mass or more, based on the entire skin cosmetic. % Or more is more preferable, and from the viewpoint of improving ease of stretching, it is preferably 15% by mass or less, more preferably 10% by mass or less, further preferably 7% by mass or less, and further more preferably 3% by mass or less. preferable. Further, the content of the component (C) is preferably 0.05 to 15% by mass, more preferably 0.1 to 10% by mass, and further 0.5 to 7% by mass with respect to the entire skin cosmetic. Preferably, 1 to 3% by mass is even more preferable.

  Component (D) used in the present embodiment is one or more compounds selected from nonionic surfactants having a polyoxyethylene group of HLB 10 or higher, ionic surfactants, and sphingosine salts.

  Among the components (D), the nonionic surfactant has a polyoxyethylene group and has a hydrophilicity of HLB 10 or more, preferably HLB 12.5 to 15.5. Nonionic surfactants used as component (D) include, for example, polyoxyethylene hydrogenated castor oil (HLB14), polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate, alkyl polyoxyethylene glyceryl, polyoxy An ethylene alkyl ether etc. are mentioned. Among these, at least one selected from polyoxyethylene hydrogenated castor oil and polyoxyethylene sorbitan monostearate is preferable.

  In addition, among the component (D), examples of the ionic surfactant include an anionic surfactant, a cationic surfactant, and an amphoteric surfactant. Examples of the anionic surfactant include fatty acid salts having 12 to 24 carbon atoms such as sodium laurate, potassium palmitate and arginine stearate; alkyl sulfate salts such as sodium lauryl sulfate and potassium lauryl sulfate; polyoxyethylene lauryl sulfate Alkyl ether sulfate ester salts such as triethanolamine; N-acyl sarcosine salts such as sodium lauroyl sarcosine; fatty acid amide sulfonates such as sodium N-stearoyl-N-methyltaurine and sodium N-myristoyl-N-methyltaurine; mono Alkyl phosphates such as sodium stearyl phosphate; polyoxyethylene alkyl ethers such as sodium polyoxyethylene oleyl ether sodium and polyoxyethylene stearyl ether sodium phosphate Long-chain sulfosuccinate such as sodium di-2-ethylhexylsulfosuccinate; monosodium N-lauroyl glutamate, sodium N-stearoyl-L-glutamate, arginine N-stearoyl-L-glutamate, sodium N-stearoyl glutamate And long-chain N-acyl glutamates such as sodium N-myristoyl-L-glutamate. Of these, fatty acid salts having 12 to 24 carbon atoms, fatty acid amide sulfonates, polyoxyethylene alkyl ether phosphates, and long-chain N-acyl glutamates are preferred, and N-stearoyl-N-methyl taurate sodium, N- Stearoyl-L-glutamate arginine and sodium polyoxyethylene stearyl ether phosphate are more preferred.

  The cationic surfactant is preferably a quaternary ammonium salt, for example, an alkyltrimethylammonium salt such as stearium trimethylammonium chloride or lauryltrimethylammonium chloride; a dialkyldimethylammonium salt, a trialkylmethylammonium salt, an alkylamine salt, etc. Is mentioned.

  Further, examples of the amphoteric surfactant include alkyl dimethylamine oxide, alkyl carboxy betaine, alkyl sulfo betaine, amide amino acid salt, and alkyl amide propyl betaine, and alkyl amide propyl betaine is preferable.

  Among the compounds of component (D) used in the present embodiment, sphingosine salts are composed of sphingosines and acidic substances. As sphingosines, naturally occurring sphingosines or synthetic products having the same structure, and derivatives thereof (hereinafter referred to as natural sphingosines) or pseudo-sphingosines having a sphingosine structure (hereinafter referred to as pseudo-sphingosines). ) Is preferred.

  Specific examples of natural sphingosine include natural sphingosine, dihydrosphingosine, phytosphingosine, sphingadienin, dehydrosphingosine, dehydrophytosphingosine, and N-alkyl isomers thereof (for example, N-methyl). . These sphingosines may be either natural (D (+)) optically active, non-natural (L (-)) optically active, natural or unnatural. Mixtures may be used. The relative configuration of the above compound may be a natural configuration, a non-natural configuration other than that, or a mixture thereof. Further, PHYTOSPHINGOSINE (INCI name: 8th Edition) and those represented by the following formula are preferable.

  These may be any of natural extracts and synthetic products, and commercially available products can be used. Examples of commercially available natural sphingosine include D-Sphingosine (4-Sphingenine) (manufactured by SIGMA-ALDRICH), DS-phytosphingosine (manufactured by DOOSAN), and phytosphingosine (manufactured by Cosmo Farm).

  Specific examples of pseudo-sphingosine include pseudo-sphingosine (i) to (iv) represented by the following formula, and 1- (2-hydroxyethylamino) -3-isostearyloxy-2-propanol.

  The sphingosine is preferably at least one selected from the group consisting of natural sphingosine, phytosphingosine and pseudo-sphingosine, more preferably pseudo-sphingosine, and pseudo-sphingosine (ii), 1 More preferred is-(2-hydroxyethylamino) -3-isostearyloxy-2-propanol.

  Acidic substances that constitute salts with these natural sphingosine, phytosphingosine, and pseudo-sphingosine include acidic amino acids such as glutamic acid and aspartic acid; inorganic acids such as phosphoric acid and hydrochloric acid; monocarboxylic acids such as acetic acid; succinic acid And dicarboxylic acids such as citric acid, lactic acid and malic acid. Among these, succinic acid of natural sphingosine, phytosphingosine, or pseudo-sphingosine (preferably pseudo-sphingosine (ii), 1- (2-hydroxyethylamino) -3-isostearyloxy-2-propanol) One or more selected from the group consisting of salts, lactates and glutamates are preferred, more preferably natural sphingosine, phytosphingosine, or pseudo-sphingosine glutamate.

  Component (D) is preferably an anionic surfactant or sphingosine salt from the viewpoint of forming an α-gel structure in combination with components (A), (B) and (C), and a stable emulsion in a small amount. From the viewpoint of obtaining, sodium N-stearoyl-N-methyltaurine, sodium polyoxyethylene stearyl ether phosphate, arginine N-stearoyl-L-glutamate, glutamate of phytosphingosine, and glutamate of pseudo-sphingosine are more preferable.

  Component (D) can be used alone or in combination of two or more in skin cosmetics. From the viewpoint of improving the anti-aging effect, the feeling of tightness, and the feeling that the skin after application is covered with cosmetics. From the viewpoint of improving storage stability, the content in the skin cosmetic is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, more preferably 0.15% by mass relative to the entire skin cosmetic. % By mass or more is more preferable, 0.3% by mass or more is more preferable, and from the viewpoint of improving ease of stretching and storage stability, it is preferably 5% by mass or less, more preferably 3% by mass or less, 2.2 mass% or less is further more preferable, and 0.8 mass% or less is further more preferable. In addition, the content of the component (D) is preferably 0.05 to 5% by mass, more preferably 0.1 to 3% by mass, and 0.15 to 2.2% by mass with respect to the entire skin cosmetic. Is more preferable, and 0.3-0.8 mass% is still more preferable. In addition, when a component (D) is an ionic surfactant and sphingosine salts, content of these components in skin cosmetics shows the mass of acid conversion. Hereinafter, the same applies to the case of indicating the mass of the component (D).

  In the present embodiment, the total content of the components (A), (B), (C) and (D) in the skin cosmetic is such that the anti-aging effect is improved, the feeling of finger tightness and the skin after application are familiar. From the viewpoint of enhancing the feeling of being covered with cosmetics, it is preferably 1.5% by mass or more, more preferably 2% by mass or more, still more preferably 3% by mass or more, and is easy to stretch. From the viewpoint of improving the thickness, it is preferably 22% by mass or less, more preferably 16% by mass or less, and further preferably 6.5% by mass or less. The total content of the components (A), (B), (C) and (D) is preferably 1.5 to 22% by mass, more preferably 2 to 16% by mass with respect to the entire skin cosmetic. Preferably, 3 to 6.5% by mass is more preferable.

  Ingredient (E) is water. The water content can be, for example, the remainder excluding components other than water in the skin cosmetic.

  In this embodiment, when skin cosmetics contain component (A)-(E), it is more preferable to combine each preferable component of the component mentioned above as component (A)-(E), and preferable content. . More preferably, component (A) is glyceryl monobehenate or monocetyl glyceryl ether, component (B) is cetanol, and component (C) is N- (hexadecyloxyhydroxypropyl) -N-hydroxyethyl. Hexadecanamide, a combination in which component (D) is stearoyl glutamate or sphingosine salts.

  The skin cosmetic of this embodiment can further contain an oily component other than those described above. For example, hydrocarbon oils such as liquid paraffin, squalane and petrolatum; ether oils such as cetyldimethylbutyl ether, ethylene glycol dioctyl ether and glycerol monooleyl ether; octyldodecyl myristate, isopropyl palmitate, butyl stearate, di-2 adipate -Ester oils such as ethylhexyl, neopentyl glycol dicaprate, and trioctanoin; higher fatty acids such as stearic acid, behenic acid, and isomyristic acid; dimethylpolysiloxane, cyclic dimethylpolysiloxane, methylphenylpolysiloxane, amino-modified silicone, carboxy Silicone oil such as modified silicone, alcohol-modified silicone, alkyl-modified silicone, polyether-modified silicone, fluorine-modified silicone; B alkyl ethyl phosphate, perfluoroalkyl polyoxyethylene phosphoric acid, a perfluoropolyether, such as fluorine-based oils such as polytetrafluoroethylene. The content of these oily components is preferably 0 to 20% by mass with respect to the entire skin cosmetic.

  Moreover, the skin cosmetic of this embodiment is an active ingredient and additive used for normal cosmetics, for example, C1-C6 monohydric alcohols, such as ethanol; ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol Polyhydric alcohols such as dipropylene glycol, polypropylene glycol, 1,3-butylene glycol, and glycerin; amino acids, peptides, and amino acid derivatives such as trimethylglycine and N-amidino-L-proline; ascorbic acid, nicotinamide, Water-soluble vitamins such as nicotinic acid; Abou extract, licorice extract, aloe extract, horsetail extract, tea extract, cucumber extract, clove extract, carrot extract, hamamelis extract, placenta extract, yeast extract, seaweed extract , Marronnier extract, yuzu extract, lemon extract, asunaro extract, royal jelly extract, eucalyptus extract, tuberose polysaccharide, asunaro extract, rice bran extract, etc .; plant hydroxide, potassium hydroxide, sodium hydroxide, triethanolamine, carbonate Bases such as sodium; acids such as citric acid, tartaric acid, lactic acid, phosphoric acid, succinic acid and adipic acid; carboxyvinyl polymer, sodium alginate, carrageenan, carboxymethylcellulose, hydroxyethylcellulose, guar gum, xanthan gum, carboxymethylchitosan, sodium hyaluronate , Oxazoline-modified silicone, N, N-dimethylaminoethyl methacrylate diethyl sulfate / N, N-dimethylacrylamide / polymethacrylate glycol glycol copolymer Thickeners; moisturizers such as 2- (2-hydroxyethoxy) ethylguanidine succinate; preservatives such as phenoxyethanol and methyl paraoxybenzoate; fragrances, etc. it can.

The skin cosmetic of the present embodiment can be produced by a normal method. For example, an oil phase component including components (A) to (D) (in the case of including an oil component, components (A) to (D) and an oil component) is heated and stirred, dissolved, and then heated (E ) Containing the aqueous phase component, followed by cooling with stirring to produce the product.
Further, when the component (D) is an ionic surfactant and a sphingosine salt, the component (D) may be blended as an ionic surfactant and a sphingosine salt. It is good also as a component (D) by mix | blending as a component, mix | blending a base with a water phase component, and neutralizing by mixing a water phase and an oil phase.

  The skin cosmetic obtained as described above is α-gel (α-type crystal), and precipitation of crystals (γ-type crystal) is suppressed. The α-gel can be confirmed by structural analysis by X-ray. The α-type structure is a hexagonal system, and the lipophilic group is oriented perpendicular to the surface of the hydrophilic base layer, and a sharp single diffraction peak appears in the vicinity of a Bragg angle of 21 to 23 °. is there.

The skin cosmetic of the present embodiment preferably has a viscosity at 25 ° C. of 1000 mPa · s to 300,000 mPa · s, more preferably 2500 mPa · s to 100,000 mPa · s, from the viewpoint of improving the elongation. More preferably, it is 5000 mPa · s to 70000 mPa · s.
In the present embodiment, the viscosity is measured by, for example, VISCOMETER TVB-10 (manufactured by Toki Sangyo Co., Ltd.). And a viscosity is measured from the conditions which can measure a low viscosity, and when it exceeds the upper limit of the viscosity on the conditions, it changes to the conditions which can measure a high viscosity next, and is measured. Specific examples of measurement conditions are shown below.
Viscosity: 250 mPa · s or more and less than 2500 mPa · s: Rotor No. M2, rotation speed 12rpm,
Viscosity 2500 mPa · s or more and less than 20000 mPa · s: Rotor No. M3, 6 rpm,
Viscosity: 20000 mPa · s or more and less than 160000 mPa · s: Rotor No. TB, 5 rpm
Viscosity: 160,000 mPa · s or more and less than 400,000 mPa · s: Rotor No. TC, 5rpm

(Examples 1 and 2, Comparative Examples 1 and 2)
The elastase activity inhibitory effect of the elastase inhibitor containing the ginger extract and the acetyl hexapeptide at the concentrations shown in Table 1 was evaluated. The ginger extract was prepared by the method described in Production Example 1 below. As the acetyl hexapeptide, Argireline (registered trademark) manufactured by Lipotec and purchased from Centerchem (Norwalk, CT) was used.

(Manufacture example 1) Manufacture of a pepper extract A shrimp was shredded, 50 vol% ethanol 500mL was added to 50 g, and it was immersed at room temperature for 2 days. A Tokyo extract obtained by filtering this was used as a Tokyo extract. When the obtained ginger extract was concentrated, the evaporation residue was 2.59 g.

(Test Example 1) Elastase (NEP) Inhibition Test of Cultured Human Fibroblasts Using Dulbecco's Modified Eagle's Medium (DMEM), 2.5 × 10 ⁴ dermal fibroblasts in a 96-well plate Sowing. On the day after sowing, the sample of the yeast extract and acetyl hexapeptide of Production Example 1 were added to the evaluation concentrations shown in Table 1 in the medium and irradiated with ultraviolet rays. After 48 hours, the culture supernatant was removed, and 10 μL of Buffer A (0.1 M Tris (: tris (hydroxymethyl) aminomethane) -HCl, pH 7.2, 1% NP-40, 0.01% SDS (: Sodium Dodecyl Sulfate)) and 30 μL of Buffer B (0.3 M NaCl, 0.1 M MES (: 2-Morpholinoethanesulfonic acid, monohydrate)) were added and incubated at 4 ° C. with shaking to lyse the cells. After 1 hour, the sample of each of the above examples diluted to 60 μL with Buffer B was added to each well to the evaluation concentration shown in Table 1 in the medium, and 2 μL of 10 mM NEP fluorescent substrate was added to the well. Incubated with. After 1 hour, 2 μL of 100 μM Phosphoramidon and 2 μL of 25 mU / mL Leucine aminopeptidase M were added to each well and further incubated at 37 ° C. After 15 minutes, the fluorescence at an excitation wavelength of 355 nm and a fluorescence wavelength of 430 nm was measured using a plate reader, and neutral endopeptidase (NEP) activity was measured. The results are shown in Table 1.

  From Table 1, it can be seen that in Examples 1 and 2, the NEP activity is suppressed as compared with Comparative Examples 1 and 2 because the combination of the yeast extract and the acetylhexapeptide is used.

(Examples 3-7 and Comparative Examples 3-4)
The oil-in-water emulsion compositions having the compositions shown in Tables 2 to 4 were produced and used as skin cosmetics for each example. The skin cosmetics obtained in Examples 3 to 6 and Comparative Examples 3 and 4 were evaluated for the presence or absence of formation of an α-gel structure by structural unfolding with X-rays. The skin cosmetics obtained in Example 3 and Comparative Examples 3 and 4 were evaluated for wrinkle improvement effects. These evaluation results are also shown in Table 2 and Table 3.

(Method for manufacturing skin cosmetics)
The oil phase components including the components (A) to (D ′) were dissolved by heating and mixing at 80 to 95 ° C. with propeller stirring (300 rpm). A water phase component containing the component (E) heated and mixed at 80 ° C. was added thereto to emulsify, and then cooled to 25 ° C. with propeller stirring (300 rpm) to obtain a skin cosmetic. In the obtained cosmetic, the component (D ′) is neutralized with all or part of L-arginine and potassium hydroxide to become N-stearoyl-L-glutamate of the component (D). Conceivable.

  In Example 7 (formulation example), all the components listed in Table 4 were combined and heated to 80 ° C., dissolved, and then cooled to 25 ° C. with propeller stirring (300 rpm) to obtain a lotion.

(Evaluation method)
(1) Evaluation of wrinkle improvement effect 16 females in their 40s to 50s who are worried about wrinkles (Cosmetic Society Wrinkle Grade), each cosmetic 0.15mL twice daily in the morning and evening, 8 per half face Applied for a week. Before starting the test and after 8 weeks of continuous wrinkles on the bare skin (washed face and cosmetics removed) in an environment with a temperature of 20-22 ° C / humidity of 45-55%. Compliant) and scored based on the wrinkle grade table. The evaluation was carried out by two professional evaluators engaged in cosmetic development and regularly evaluating wrinkles, and evaluated in 0.5 increments. About this wrinkle score, the average wrinkle score change amount (Δ) obtained by averaging the changes after 16 weeks of continuous use from 16 panelists was judged based on the following criteria, and the wrinkle improvement effect was evaluated.
Improvement: Wrinkle score change amount (Δ) is Δ ≦ −0.4
Slight improvement: wrinkle score change (Δ) is −0.4 <Δ ≦ −0.2
No change: wrinkle score change amount (Δ) is −0.2 <Δ ≦ 0
Deterioration: Wrinkle score change amount (Δ) is 0 <Δ

Structural analysis by X-ray: From the wide-angle X-ray diffraction peak of 2θ = 10-30 °, the method of Wilson and Ott (Wilson, DA and Ott, E., J. Chem. Phys. , 2, 231-238 (1934)), the crystal structure was determined. In Tables 2 and 3, the evaluation of the crystal structure is shown by the following criteria.
A: α-type structure was confirmed.
B: α-type structure is not confirmed.

  From Table 2 and Table 3, it was confirmed that all of the skin cosmetics of Examples 3 to 6 have an α-gel structure. Further, from Table 2, in Comparative Examples 3 and 4 containing either one of the yeast extract and the acetyl hexapeptide, no wrinkle improving effect was observed, but in combination with the yeast extract and the acetyl hexapeptide. The skin cosmetic of Example 3 used showed a wrinkle improving effect.

Claims (6)

  An elastase inhibitor comprising a salmon extract and an acetyl hexapeptide.   The elastase inhibitor according to claim 1, comprising 0.00001 to 5% by mass of the ginger extract as an evaporation residue with respect to the whole elastase inhibitor.   The mass ratio (shower extract / acetylhexapeptide) of the content of the yeast extract (evaporation residue) to the content of the acetylhexapeptide in the elastase inhibitor is 0.01 to 2,000. Or the elastase inhibitor according to 2.   A skin cosmetic comprising the elastase inhibitor according to any one of claims 1 to 3.   The skin cosmetic according to claim 4, which has an α-gel structure. The following components (A) to (E):
(A) An organic compound having two or more hydroxyl groups, an inorganic value of 220 to 450, and an organic value of 300 to 1000,
(B) an organic compound having one hydroxyl group and having an inorganic value of 100 to 200 and an organic value of 280 to 700;
(C) Ceramides,
(D) one or more compounds selected from the group consisting of nonionic surfactants having a polyoxyethylene group of HLB 10 or higher, ionic surfactants and sphingosine salts, and (E) water, The skin cosmetic according to claim 4 or 5, wherein the total content of the components (A), (B), (C) and (D) with respect to the entire cosmetic is 1.5 to 22% by mass.