JP2016027034A - Composition for external use - Google Patents

Abstract

An object of the present invention is to provide a composition for external use with a novel composition that has an excellent collagen production-promoting effect and can suppress, prevent, and improve age-related wrinkles, sagging, and the like. (A) the following formula (1); or 1) or a pharmaceutically acceptable salt thereof. [Selection figure] None

Description

  The present invention relates to a composition for external use.

  Skin aging manifests itself as surface morphology changes such as wrinkles, tarmi, dullness, and spots. These changes are caused by a decrease in the ability of epidermal cells to proliferate with age, thinning of the epidermis, thickening of the stratum corneum, a decrease in collagen fibers in the dermis, and the like.

  Collagen is the main protein that constitutes the connective tissue of animals and occupies nearly 30% of the total protein of the human body. Since the main function of collagen is in the formation of a skeletal structure of living tissue, it is widely distributed in skin, cartilage tissue, cornea, heart, liver, etc. as the main component constituting the skeletal structure of animal tissue form. Collagen acts specifically on cell adhesion, cell differentiation and proliferation, and also has a role as a regulator of cell function. Collagen loss is caused by corneal disorders such as corneal ulcers, arthritis ( It may cause various diseases such as osteoarthritis and osteoarthritis), joint disorders such as rheumatism, and inflammatory diseases.

  In the dermal extracellular matrix of the skin, collagen fibers maintain a network morphology by forming a mesh-like bundle. Collagen fibers become thick and linear fiber bundles when they mature and proliferate and crosslink formation proceeds, giving moderate elasticity in young skin. However, in aging skin, collagen fibers in the dermal extracellular matrix are remarkably reduced, and the inherent elasticity is lost. As a result, wrinkles and tarmi are formed on the skin. Changes in the structure of collagen fiber bundles in hairless mice due to photoaging have been examined in detail (see Non-Patent Document 1). Collagen fiber bundles are formed so that wrinkles are formed in hairless mice irradiated with UVB and coincide with the formation of wrinkles. It has been shown that the structure collapses and skin elasticity decreases. It is also known that collagen is excellent in water retention function.

  The aging of the skin can be suppressed and improved to some extent by cosmetics, pharmaceuticals, etc. (see Non-Patent Document 2), for example, cosmetics containing hyaluronic acid and the collagen, moisturizing action and film forming action Herbal medicine extracts and cosmetics containing chemically synthesized substances are used. Attempts have also been made to promote the production of hyaluronic acid and collagen by improving the metabolism of the skin itself.

  Examples of components that promote collagen production include, for example, retinoic acid (see Non-patent Document 3), three amino acids composed of glycine, proline, and alanine (see Patent Document 1), licorice, Sohakuhi, aloe, sugina, goldfish , Plant extracts such as agar, moth, and gentian (see Patent Document 2), TGF-β, ascorbic acids, collagen degradation products (see Patent Document 3), and the like are known. Furthermore, specific peptides having specific amino acid sequences can be obtained by using low-molecular-weight betaine in combination with ascorbic acids (see Patent Document 4) or by using δ-tocopheryl retinoate in combination (see Patent Document 5). It has also been reported that when used in combination (see Patent Document 6), the collagen synthesis promoting action is enhanced.

  Patent Document 7 describes a gelling agent composed of a specific lipid peptide, but there is no specific description of a composition for external use using this gelling agent. There is no description or suggestion that the peptide has an effect of promoting collagen production.

JP-A-7-194375 JP 2001-206835 A JP 2000-309521 A JP 2005-239645 A JP 2005-263794 A JP 2008-1661 A International Publication No. 2010/013555

Fragrance Journal 4, p36-37, 1998 Edited by Takeo Mitsui, New Cosmetic Science, 2nd edition, Nanzan-do, 2001, p. 42-50 R. Marks et al., British Journal of Dermatology, 122, 91-98, 1990.

  Under such circumstances, the present invention provides an anti-aging composition for anti-aging that has an excellent collagen production-promoting effect and can suppress, prevent, and improve wrinkles, tarmi and the like associated with aging. The purpose is to provide.

The invention for solving the above-mentioned problem, that is, the gist of the present invention is as follows.
<1> (A) The following formula (1)

（式中、Ｒ^１は、炭素数９〜１９の、飽和脂肪族基又は1個の不飽和結合を有する脂肪族基である。ｍは、０又は１である。）で表される脂質ペプチド又はその薬学的に許容される塩（以下、「（Ａ）成分」ともいう）を含む、抗老化用の外用組成物。
＜２＞ビタミンＣ類をさらに含む、＜１＞記載の外用組成物。
＜３＞皮膚のシワ若しくはタルミを抑制、改善又は予防するための、＜１＞又は＜２＞記載の外用組成物。
＜４＞肌のハリ・弾力の低下を抑制、改善又は予防するための、＜１＞又は＜２＞記載の外用組成物。
＜５＞コラーゲン産生促進のための、＜１＞〜＜４＞のいずれか記載の外用組成物。＜６＞（Ａ）下記式（１）

（式中、Ｒ^１は、炭素数９〜１９の、飽和脂肪族基又は1個の不飽和結合を有する脂肪族基である。ｍは、０又は１である。）で表される脂質ペプチド又はその薬学的に許容される塩を用いる、コラーゲン産生促進方法。

(Wherein R ¹ is a saturated aliphatic group having 9 to 19 carbon atoms or an aliphatic group having one unsaturated bond. M is 0 or 1.) Or the external composition for anti-aging containing the pharmaceutically acceptable salt (henceforth "(A) component").
<2> The composition for external use according to <1>, further comprising vitamin C.
<3> The composition for external use according to <1> or <2>, for suppressing, improving or preventing skin wrinkles or talmi.
<4> The composition for external use according to <1> or <2> for suppressing, improving or preventing a decrease in skin elasticity and elasticity.
<5> The composition for external use according to any one of <1> to <4>, for promoting collagen production. <6> (A) Formula (1) below

(Wherein R ¹ is a saturated aliphatic group having 9 to 19 carbon atoms or an aliphatic group having one unsaturated bond. M is 0 or 1.) Or the collagen production promotion method using the pharmaceutically acceptable salt thereof.

  The composition for external use of the present invention has an excellent collagen production promoting effect, and can suppress / prevent / improve wrinkles, tarmi and the like accompanying aging. Moreover, the composition for external use of this invention is excellent also in cell growth promotion ability, and can suppress the aging by the deterioration of skin effectively by activating a cell. As described above, the external composition of the present invention is an external composition for anti-aging with a novel structure that is excellent in collagen production promoting effect and cell activation effect. Moreover, since (A) component also has an effect | action as a gelatinizer, the composition for external use of this invention can be made into a suitable form as needed. Since it has such properties, the composition for external use of the present invention is widely used in cosmetics, quasi-drugs and / or pharmaceuticals as an anti-aging external composition having a collagen production promoting effect and a cell activation effect. Can do.

FIG. 1 is a view showing the collagen production promoting effect of an external composition which is one of the embodiments of the present invention. FIG. 2 is a diagram showing the cell growth promoting effect of the composition for external use which is one of the embodiments of the present invention.

  Hereinafter, the present invention will be described in detail.

<External composition>
The composition for external use of this invention contains the lipid peptide represented by following formula (1), or its pharmacologically acceptable salt ((A) component). By including the component (A), the composition for external use of the present invention can have a collagen production promoting effect and a cell activation effect, and can be in a gel form. According to the composition for external use of the present invention, it is possible to suppress, improve and prevent a decrease in the elasticity and elasticity of the skin, and to suppress, prevent and improve wrinkles, tarmi and a tangled line. In addition, the skin can be kept smooth by the collagen production promoting effect and the like, and the texture and plumpness of the skin can be maintained and improved. In addition, the composition for external use of this invention may contain various arbitrary components for the purpose of improving the effect of this invention other than (A) component. Hereinafter, (A) component, a solvent, and arbitrary components are demonstrated.

  Here, the “collagen production promoting effect” refers to an effect of increasing the amount of collagen produced when an external composition is allowed to act on cells or skin, compared to the case where the external composition is not allowed to act. means. In addition, the “cell activation effect” means an effect of further promoting cell proliferation when an external composition is allowed to act on cells as compared to the case where the external composition is not allowed to act. In a specific embodiment, fibroblasts, particularly skin fibroblasts are used as the cells.

[(A) component]
Component (A) is a lipid peptide represented by the following formula (1) or a pharmaceutically acceptable salt thereof, consisting of a lipid-soluble long-chain lipid moiety (alkylcarbonyl group) and a peptide. It consists of parts. Furthermore, the peptide moiety is composed of histidine or glycine-histidine.

In the above formula, R ¹ is a saturated aliphatic group having 9 to 19 carbon atoms or an aliphatic group having one unsaturated bond. m is 0 or 1.

R ¹ is a saturated aliphatic group having 11 to 17 carbon atoms or an aliphatic group having one unsaturated bond from the viewpoint of the collagen production promoting effect and cell activation effect of the externally applied composition of the present invention. A saturated aliphatic group having 11 to 17 carbon atoms is more preferable, and a linear saturated aliphatic group having 11 to 17 carbon atoms is more preferable.

Examples of R ¹ include a nonyl group, a decanyl group (capryl group), an undecanyl group, a dodecanyl group (lauryl group), a tridecanyl group, a tetradecanyl group (mistyl group), a pentadecanyl group, a hexadecanyl group (palmityl group), and a heptadecanyl group. , Octadecanyl group (stearyl group), nonadecanyl group, nonenyl group, decenyl group, undecenyl group, dodecenyl group, tridecenyl group, tetradecenyl group, pentadecenyl group, hexadecenyl group, heptadecenyl group, octadecenyl group, nanodecenyl group and the like. Among these, tetradecanyl group (myristyl group), hexadecanyl group (palmityl group), and octadecanyl group (stearyl group) are preferable from the viewpoint of collagen production promoting effect and cell activation effect of the external composition of the present invention.

  As the preferred component (A) in the composition for external use of the present invention, when m is 0, N-nonyloyl histidine, N-decanoyl histidine, N-undecanoyl histidine, N-lauroyl histidine, N-tri Decanoyl histidine, N-mistoyl histidine, N-pentadecanoyl histidine, N-palmitoyl histidine, N-heptadecanoyl histidine, N-stearoyl histidine, N-nonadecanoyl histidine, N-icosanoyl histidine, etc. Can be mentioned.

  When m is 1, N-nonyloylglycinyl histidine, N-decanoyl glycinyl histidine, N-undecanoyl glycinyl histidine, N-lauryl glycinyl histidine, N-tridecanoyl glycinyl histidine, N -Mistoyl glycinyl histidine, N-pentadecanoyl glycinyl histidine, N-palmitoyl glycinyl histidine, N-heptadecanoyl glycinyl histidine, N-stearoyl glycinyl histidine, N-nonadecanoyl glycinyl histidine, N -Icosanoyl glycinyl histidine etc. are mentioned.

  In addition, as a histidine part in (A) component, either L or R optically active histidine can be used. Since the composition for external use of the present invention is suitably used for cosmetics, medicines, quasi drugs, etc., it is particularly preferable to use a lipid peptide having L-form histidine present in the living body.

  Examples of the pharmaceutically acceptable salt of the lipid peptide represented by the above formula (1) include alkali metal salts such as lithium salt, sodium salt, potassium salt and calcium salt as salts corresponding to the carboxyl group of histidine. However, examples of the salt corresponding to the imidazole group of histidine include inorganic acid salts such as hydrochloride, sulfate, and phosphate, and organic acid salts such as acetate, carbonate, citrate, and succinate.

  The lipid peptide and its pharmaceutically acceptable salt, which are the component (A) described above, can be produced by methods known to those skilled in the art. For example, by the peptide solid phase synthesis method, amino acids constituting the lipid peptide are linked, and the N-terminal of the amino acid at the terminal position when viewed from the solid phase is reacted with the fatty acid serving as the lipid portion, and if necessary, the salt It can manufacture by setting it as the form of this. Moreover, (A) component can be manufactured by starting from a fatty acid by a liquid phase method, connecting an amino acid to this, and making it into the salt form as needed.

  In this invention, (A) component may be used individually by 1 type, and may be used in combination of 2 or more types arbitrarily. The content of the component (A) in the entire external composition of the present invention (in 100% by weight) is usually 0.0001 to 5% by weight from the viewpoint of collagen production promotion effect, cell activation effect and the like. It is preferable that the amount is .0005 to 3% by weight, and more preferably 0.001 to 1.5% by weight.

[solvent]
The composition for external use of the present invention contains water, alcohol, hydrophilic organic solvent, fatty acid, higher fatty acid ester, glyceride or hydrophobic organic solvent, or a miscible mixed solvent thereof. When the component (A) is added to these solvents at a specific ratio, gelation occurs, and an external composition having an appropriate viscosity and good skin compatibility can be obtained.

  The solvent preferably functions as a base or carrier in the composition for external use, and is an aqueous solvent such as water, liquid paraffin, squalane, petrolatum, gelled hydrocarbon (such as plastibase), ozokerite, α-olefin oligomer, light fluid Hydrocarbons such as paraffin; methyl polysiloxanes such as polymethylsilsesquioxane, cross-linked methyl polysiloxane, highly polymerized methyl polysiloxane, cyclic silicone, alkyl-modified silicone, cross-linked alkyl-modified silicone, amino-modified silicone, polyether Modified silicone, polyglycerol modified silicone such as lauryl dimethicone polyglycerol-3 crosspolymer, crosslinked polyether modified silicone, crosslinked alkyl polyether modified silicone, silicone / alkyl chain co-modified polyether modified Silicone oils such as silicone, silicone-alkyl chain co-modified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicone, phenyl-modified silicone, silicone resin; cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol Higher alcohols such as; cellulose derivatives such as ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose; polyvinylpyrrolidone; carrageenan; polyvinyl butyrate; polyethylene glycol; dioxane; butylene glycol adipic acid polyester; isopropyl myristate, octyldodecyl myristate, Isopropyl palmitate, cetyl palmitate, Esters such as octyl luminate, isononyl isononanoate, pentaerythritol tetra-2-ethylhexanoate, glyceryl tri-2-ethylhexanoate, jojoba oil; polysaccharides such as dextrin, maltodextrin; ethanol, isopropanol, etc. Alcohol etc. are mentioned. Of these, aqueous solvents are preferred, with water being particularly preferred. When the external composition of the present invention contains water, the amount of the composition can be appropriately selected in consideration of the feeling on the skin and the effects of the present invention. 0.001 to 99.5% by weight, preferably 0.01 to 90% by weight, more preferably 0.1 to 60% by weight, and most preferably 1 to 20% by weight.

[Optional ingredients]
The external composition of the present invention preferably further contains vitamins in addition to the component (A) for the purpose of improving the effects of the present invention. In addition, a vitamin may be used individually by 1 type, respectively, and 2 or more types may be used in arbitrary combinations. In addition to these, bactericides, polyhydric alcohols, glycol ethers, thickeners and the like may be used as optional components as long as the effects of the present invention are not impaired. In addition, when the compound specifically illustrated as each component overlaps, it should just be contained as any component.

(Vitamins)
Examples of the vitamins include retinol derivatives such as retinol, retinol acetate, and retinol palmitate, retinal, retinoic acid, methyl retinoic acid, ethyl retinoic acid, retinol retinoic acid, d-δ-tocopheryl retinoate, and α-tocotic acid. Vitamin A such as ferryl retinoate and β-tocopheryl retinoate; provitamin A such as β-carotene, α-carotene, γ-carotene, δ-carotene, lycopene, zeaxanthin, cryptoxanthin and echinone; δ-tocopherol , Α-tocopherol, β-tocopherol, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, δ-tocopherol, tocopherol nicotinate, etc .; Riboflavin, flavin mononucleoti Vitamin B2 such as flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, sodium riboflavin 5'-phosphate, riboflavin tetranicotinate; nicotinic acids such as methyl nicotinate, nicotinic acid, nicotinamide; Ascorbyl stearate, L-ascorbyl dipalmitate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, Vitamin Cs such as ascorbic acid glucoside and 3-O-ethylascorbic acid; methyl hesperidin, ergocalciferol, cholecalci Vitamin Ds such as erol; Vitamin Ks such as phylloquinone and farnoquinone; dibenzoylthiamine, dibenzoylthiamine hydrochloride, thiamine hydrochloride, thiaminecetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monolin Acid salt, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate, thiamine triphosphate monophosphate, etc. Vitamin B1 of vitamin B6 such as pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5'-phosphate pyridoxal, pyridoxamine hydrochloride, cyanocobalamin, hydroxocobalamin, deoxya Vitamin B12 such as nosylcobalamin; folic acid such as folic acid, pteroylglutamic acid; pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-pantethein, D-panthetin, coenzyme A, pantothenyl ether Pantothenic acids such as biotin; biotins such as biotin and biocytin; and other vitamin-like agents such as carnitine, ferulic acid, α-lipoic acid, orotic acid, and γ-oryzanol. Among these, from the viewpoint that the effect of enhancing the collagen production promoting effect of the composition for external use of the present invention is high, ascorbyl stearate, L-ascorbyl dipalmitate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), Vitamin Cs such as ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, and ascorbyl glucoside are preferred, and L-ascorbic acid is more preferred. In vitamin C, a part of the vitamin C derivative is converted into vitamin C by an enzyme in the living body and acts. For example, it is considered that ascorbic acid glucoside is decomposed into ascorbic acid and glucose in vivo, and ascorbic acid acts to enhance the collagen production promoting effect.

  When the vitamins are blended, the amount used can be appropriately selected in consideration of the feeling on use on the skin, the collagen production promoting effect, and the cell activation effect. It is 0001-30 weight%, Preferably it is 0.0005-25 weight%, More preferably, it is 0.001-20 weight%.

(Fungicide)
The composition for external use of the present invention can contain 1,2-alkanediol as a fungicide. The 1,2-alkanediol used in the present invention includes the following formula (2):

R ² —CH (OH) —CH ₂ —OH (2)

1,2-alkanediol represented by the following formula.

In the above formula, R ² is an alkyl group having 2 to 8 carbon atoms. This alkyl group may be linear or branched.

  Examples of the 1,2-alkanediol contained in the composition for external use of the present invention include 1,2-butanediol, 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, 1, Examples include 2-octanediol and 1,2-decanediol. Of these, 1,2-hexanediol and 1,2-octanediol are preferable, and 1,2-octanediol is more preferable.

  The content of 1,2-alkanediol in the entire composition for external use of the present invention (in 100% by weight) is preferably 0.01 to 15% by weight from the viewpoint of antibacterial properties, and 0.1 to 10%. More preferably, it is% by weight.

  The composition for external use of the present invention can contain a quaternary ammonium salt type fungicide as a fungicide. The quaternary ammonium salt fungicide used in the present invention includes the following formula (3):

で表される第４級アンモニウム塩が挙げられる。

The quaternary ammonium salt represented by these is mentioned.

In the above formula (3), ^{R 3} and ^{R 4} are each independently an alkyl group having 1 to 3 carbon atoms. R ⁵ is a group represented by the following formula (4). R ⁶ is an alkyl group or alkenyl group having 1 to 4 carbon atoms. X ⁻ is a chloride ion or a bromide ion.

In the above formula (4), ^{R 7} is an alkyl group having 1 to 4 carbon atoms. n is an integer of 3 to 60.

R ⁷ is preferably a methyl group, and n is preferably an integer of 9 to 41. As the quaternary ammonium salt type bactericide contained in the composition for external use of the present invention, R ⁵ in the formula (3) is a polyoxypropylene group which is a polymer of 9 units to 41 units of oxypropylene, For example, polyoxypropylene chloride (9) methyldiethylammonium chloride, polyoxypropylene chloride (25) methyldiethylammonium chloride, polyoxypropylene chloride (40) methyldiethylammonium chloride and the like are preferable. Examples of these commercially available products include Emcol CC-9, 36, 42 manufactured by Witco Chemical Company and Adeka Coal EC-CC-9, 36, 42 manufactured by Asahi Denka Kogyo Co., Ltd. In addition to these, cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride and the like can also be mentioned as preferable examples.

  Of these, cetylpyridinium chloride, benzalkonium chloride, and benzethonium chloride are preferred from the viewpoint of antibacterial properties and safety.

  The composition for external use of this invention can use a slightly water-soluble active disinfectant as a disinfectant. Here, the slightly water-soluble active fungicide means a substance having a disinfecting / antibacterial ability, which has a solubility in water at 25 ° C. of less than 1% by weight (w / v). This sparingly water-soluble active disinfectant is roughly classified into phenolic substances and alcoholic substances.

  Examples of the phenolic substance include triclosan, triclocarbanilide, methyl paraben, ethyl paraben, propyl paraben, isopropyl methyl phenol, and the like. Examples of alcohol-based substances include dodecyl alcohol and decyl alcohol.

  The slightly water-soluble active fungicide may be composed of a single substance, may be composed of a mixture of a plurality of phenolic substances, or may be composed of a mixture of a plurality of alcoholic substances. It may be configured such that a phenolic substance and an alcoholic substance are mixed.

  The composition for external use of this invention can use what is used as a disinfectant of cosmetics, a quasi-drug, or a pharmaceutical without limitation as another disinfectant. For example, decalinium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, alkyldiaminoethylglycine hydrochloride, cetylpyridinium chloride, sodium benzoate, chlorobutanol, salicylic acid, gluconic acid, thymol, hexachlorophene, berberine, terbinafine hydrochloride, lysozyme chloride, Salicylic acid, salicylate, sulfur or sulfur compounds, hinokitiol, triclosan, trichlorocarbanilide, halocarban, chlorophenesine, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl paraoxybenzoate, paraoxybenzoic acid Propyl, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, and biguanide compounds, etc. Include that at least one Chi.

  Among these other disinfectants, from the viewpoint of antibacterial properties and safety, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, decalinium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, chloride Cetylpyridinium and thymol are preferred. In addition, content of the other disinfectant in the external composition of this invention is a density | concentration of 0.0001-1 weight% in the whole external composition of this invention (in 100 weight%).

(Polyhydric alcohol)
The composition for external use of this invention can contain a polyhydric alcohol. As the polyhydric alcohol that can be included in the composition for external use of the present invention, those used in cosmetics, quasi drugs or pharmaceuticals can be used without limitation. For example, glycols (ethylene glycol, diethylene glycol, propylene glycol, isopropylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol, 1,3-butylene glycol, pentylene glycol, etc.), glycerin, diglycerin, triglycerin, polyglycerin Sorbitol, alkanediol (propanediol, 3-methyl-1,3-butanediol, pentanediol, etc.) and the like. Among these, from the viewpoint of formulation considering the feeling of use and the like, propylene glycol, dipropylene glycol, 1,3-butylene glycol, pentylene glycol, glycerin, diglycerin, sorbitol, alkanediol (propanediol, pentanediol, Hexanediol) and the like, and dipropylene glycol, 1,3-butylene glycol, and pentylene glycol are more preferable. These polyhydric alcohols can be used alone or in combination of two or more.

  The content of the polyhydric alcohol in the composition for external use of the present invention is preferably 0.01% by weight or more, more preferably 0.1% by weight or more in the entire composition for external use of the present invention (100% by weight), and 0 More preferably, it is 5% by weight or more. Moreover, 97 weight% or less is preferable in the whole external composition (100 weight%) of this invention, 50 weight% or less is more preferable, and 30 weight% or less is still more preferable. If it is the said range, in addition to the effect of this invention, a moisturizing force and a favorable usability | use_condition can be provided to an external composition.

(Glycol ether)
The composition for external use of this invention can contain glycol ether. As a glycol ether used for the composition for external use of this invention, what is used for cosmetics, a quasi-drug, or a pharmaceutical can be used without a restriction | limiting. For example, ethylene glycol based glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, and ethylene glycol monopropyl ether; diethylene glycol based glycols such as diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, and diethylene glycol monopropyl ether Ethers; propylene glycol-based glycol ethers such as propylene glycol monoethyl ether and propylene glycol monopropyl ether; and dipropylene glycol-based glycol ethers such as dipropylene glycol monoethyl ether and dipropylene glycol monopropyl ether Is mentioned. Among these, ethylene glycol and diethylene glycol glycol ethers are preferred, ethylene glycol monomethyl ether and diethylene glycol monoethyl ether are more preferred, and diethylene glycol monoethyl ether is particularly preferred. These polyhydric alcohols can be used alone or in combination of two or more.

  The content of the glycol ether in the external composition of the present invention is preferably 0.01% by weight or more, more preferably 0.1% by weight or more, based on the entire external composition of the present invention (in 100% by weight). 5% by weight or more is more preferable. Moreover, 97 weight% or less is preferable in the whole external composition of this invention (in 100 weight%), 75 weight% or less is more preferable, and 50 weight% or less is further more preferable. If it is the said range, in addition to the effect of this invention, a moisturizing force and a favorable usability | use_condition can be provided to an external composition.

(Thickener)
The composition for external use of this invention can contain a thickener. Thereby, it can be set as the external composition which is familiar with skin and excellent in a usability | use_condition.

  As such thickeners, those used as thickeners for cosmetics, quasi drugs or pharmaceuticals can be used without limitation. For example, guar gum, locust bean gum, carrageenan, xanthan gum, dextran, methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, sodium alginate, propylene glycol alginate, dextran , Polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, alkyl methacrylate copolymer, sodium polyacrylate, polyethylene glycol, bentonite, dextrin fatty acid ester, pectin, (hydroxyacrylate) (Acryloyldimethyltaurine Na) copolymer, dimethyl distearyl ammonium hectorite, (acryloyl dimethyl taurine ammonium / vinyl pyrrolidone) copolymer, (acryloyl dimethyl taurine ammonium behenes-25 methacrylate) cross copolymer, (acryloyl dimethyl taurine ammonium / steale methacrylate) -25) Cross polymers, polyethylene glycol distearate, ethylene glycol triisostearate, polyoxyethylene (20) methylglucoside triisostearate, and the like. Among these, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, xanthan gum, alkyl methacrylate methacrylate copolymer (hydroxyethyl acrylate / acryloyldimethyltaurine Na) More preferred are copolymers and (acryloyldimethyltaurate ammonium / vinylpyrrolidone) copolymers. These thickeners may be used alone or in any combination of two or more.

  The content of the thickener in the external composition of the present invention is preferably 0.0001 to 20% by weight, more preferably 0.001 to 10% by weight in the entire external composition of the present invention (in 100% by weight). 0.05 to 5% by weight is more preferable. If content of a thickener is the said range, it can be set as the composition for external use which is familiar with skin and excellent in a usability | use_condition.

(Other ingredients)
In addition to the above-described components, the composition for external use of the present invention has an ultraviolet scattering component, an ultraviolet absorbing component, a component having a DNA damage preventing and / or repairing action in addition to the above-described components. 1 type or 2 types of whitening component, anti-inflammatory component, cell activation component, astringent component, antioxidant component, anti-aging component, moisturizing component, keratin softening component, blood circulation promoting component, sebum adsorbing component, hair growth component You may mix | blend combining a seed | species or more. These components are not particularly limited as long as they can be used in the fields of pharmaceuticals, quasi drugs, cosmetics, and the like, and arbitrary components can be appropriately selected and used. Moreover, what corresponds to the following several components shall be added as a component of arbitrary efficacy among them.

  Examples of the ultraviolet scattering component include inorganic compounds such as zinc oxide, titanium oxide, iron oxide, cerium oxide, zirconium oxide, titanium silicate, zinc silicate, anhydrous silicic acid, cerium silicate, hydrous silicic acid, and the like. These inorganic compounds are coated with inorganic powders such as hydrous silicic acid, aluminum hydroxide, mica and talc, or compounded with resin powders such as polyamide, polyethylene, polyester, polystyrene, nylon, and silicon oil and fatty acids. The thing etc. which processed with aluminum salt etc. are mentioned. Of these, inorganic compounds such as zinc oxide, titanium oxide and iron oxide, and those inorganic compounds coated with inorganic powder such as aluminum hydroxide, hydrous silicic acid, mica and talc, and silicon oil are preferable. In the case of blending an ultraviolet scattering component, the amount used can be appropriately selected in consideration of the feeling of use and effects on the skin, but is preferably 0.001 to 35% by weight, for example, based on the total amount of the external composition of the present invention. Is 0.1 to 25% by weight.

  Examples of the ultraviolet absorbing component include 2-methoxyhexyl paramethoxycinnamate, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, 2,4,6-tris [4- (2- Ethylhexyloxycarbonyl) anilino] -1,3,5-triazine, dimethoxybenzylideneoxoimidazolidinepropionate 2-ethylhexyl, 2,4-bis-[{4- (2-ethylhexyloxy) -2-hydroxy} -phenyl] -6- (4-methoxyphenyl) -1,3,5-triazine and the like. When the ultraviolet absorbing component is blended, the amount used can be appropriately selected in consideration of the feeling of use and effects on the skin, but it is preferably 0.01 to 20% by weight, for example, with respect to the total composition for external use of the present invention. Is 0.1 to 15% by weight.

  Examples of the whitening component include hydroquinone, placenta, arbutin, kojic acid, ellagic acid, phytic acid, tranexamic acid, 4-n-butylresorcinol, chamomile extract, vitamin A or a derivative thereof, pantothenic acid or a derivative thereof, and the like. And the like. Furthermore, a plant component having a whitening effect may be used as a whitening component. Examples of such plant components include Iris (Iris), Almond, Aloe, Ginkgo, Oolong Tea, Ages, Ogon, Ouren, Hypericum, Adriatic, Seaweed, Cuckoo, Gardenia, kujin, chlorella, goby wheat, rice, rice haiga, oryzanol, rice bran, saishin, salamander, perilla, peonies, senkyu, sakuhakuhi, soybeans, natto, tea, touki, daikinsen, garlic, hamamelis, safflower, safflower, buttonpi, yokui Toki, Amethyst, Acaciatic, Acebi Warabi, Inohaki, Enoki, Oyster (Diospyros kaki), Cattle, Black Bean, Gentian, Genzin, Salsa, Sweet Bean Shouma, Juju, Sage, Zenko, Daikon, Azalea, Tsu Ingredients derived from horsetail, tocin, nigaki, parsley, holly, hops, malbahagi, clove, licorice, grapefruit and the like. Preferably, Iris (Iris), Aloe, Ginkgo, Oolong tea, Ages, Ogon, Oulen, Hypericum, Olysam, Seaweed, Cuckoo, Gardenia, Kujin, Gobaishi, Wheat, Rice, Rice bran, Saishin, Salamander, Perilla, Peonies, Senkyu , Sakuhakuhi, Tea, Toki, Toki-Senka, Hamelis, Safflower, Buttonpi, Yokuinin, Amethyst, Acalysia, Enoki, Oyster (Diospyros kaki), Cattle, Black Bean, Gentian, Salsa, Soyagen, Juju, Sage, Zenko, Daikon, Tsuji It is a component derived from Tsukuhashigi, Toshin, Nigaki, Parsley, Holly, Hop, Clove, Licorice, Grapefruit, and Toki, and more preferably Iris (Iris), Aloe, Ginkgo, Ages, Ogon, Oure , Hypericum, gardenia, cucumber, rice, rice bran, saishin, peony, senkyu, sakuhakuhi, tea, touki, kansen, hamamelis, safflower, buttonpi, amethyst, asenyaku, enoki, oyster (Diospyros kaki), sage, daikon , Parsley, hops, licorice, grapefruit and yokuinin-derived components. Among these, Iris root extract, which is a component derived from Iris (iris), brown algae extract, Calaf comb extract, and aloe extract, which are components derived from seaweed, are more preferable. When these plant components are used in the composition for external use of the present invention, the form of the plant component is not particularly limited, but can be usually used in the form of a plant extract (plant extract), an essential oil or the like. In addition, the inside of () in the said plant component is the scientific name of the plant, an alias, or a crude drug name. When the whitening component described above is blended in the external composition of the present invention, the amount used can be appropriately selected in consideration of the feeling of use and effects on the skin, but for example 0.0003 relative to the entire external composition. -10 wt%, preferably 0.01-5 wt%. When the plant extract is used, the amount used is 0.00001 to 20% by weight, preferably 0.0001 to 15% by weight, more preferably 0. 001 to 10% by weight.

  Examples of the anti-inflammatory component include allantoin, calamine, tranexamic acid, glycyrrhizic acid or a derivative thereof or a salt thereof, glycyrrhetinic acid or a derivative thereof or a salt thereof, zinc oxide, guaiazulene, tocopherol acetate, pyridoxine hydrochloride, menthol, camphor , Turpentine oil, indomethacin, salicylic acid or a derivative thereof. Preferred is glycyrrhizic acid or a derivative thereof or a salt thereof (for example, dipotassium glycyrrhizinate), glycyrrhetinic acid or a derivative thereof or a salt thereof, or zinc oxide. When an anti-inflammatory component is blended, the amount used can be appropriately selected in consideration of the feeling of use and effects on the skin, but it is, for example, 0.0003 to 10% by weight, preferably with respect to the entire external composition of the present invention. Is 0.01 to 5% by weight.

  Examples of the cell activation component include amino acids such as γ-aminobutyric acid and ε-aminocaproic acid: α-hydroxy acids such as glycolic acid and lactic acid: tannin, flavonoids, saponins, allantoin, and photosensitizer 301. It is done. When the cell activating component is blended, the amount used can be appropriately selected in consideration of the feeling of use and effects on the skin. For example, 0.0003 to 10% by weight relative to the total composition for external use of the present invention, Preferably it is 0.01 to 5 weight%.

  Examples of the astringent component include metal salts such as alum, chlorohydroxyaluminum, aluminum chloride, allantoin aluminum salt, zinc sulfate, and potassium aluminum sulfate; organic acids such as tannic acid, citric acid, lactic acid, and succinic acid. it can. When blending an astringent component, the amount used can be appropriately selected in consideration of the feeling of use and effects on the skin, but for example 0.0003 to 10% by weight, preferably based on the total composition for external use of the present invention. 0.01 to 5% by weight.

  Examples of the antioxidant component include butylhydroxyanisole, dibutylhydroxytoluene, sodium hydrogensulfite, sodium pyrosulfite, flavonoid, glutathione, glutathione peroxidase, glutathione-S-transferase, catalase, superoxide dismutase, thioredoxin, taurine, thiotaurine, Examples include hypotaurine, L-cysteine hydrochloride, astaxanthin and the like. When the antioxidant component is blended, the amount used can be appropriately selected in consideration of the feeling of use and effects on the skin, but it is preferably, for example, 0.00001 to 10% by weight, preferably based on the total composition for external use of the present invention. Is 0.0001 to 5 wt%, more preferably 0.001 to 5 wt%.

  Examples of the anti-aging component include pangamic acid, ursolic acid, turmeric extract, sphingosine derivative, silicon, silicic acid, N-methyl-L-serine, mevalonolactone, and the like. When blending an anti-aging component, the amount used can be appropriately selected in consideration of the feeling of use and effects on the skin, but for example 0.0003 to 10% by weight, preferably with respect to the total composition for external use of the present invention. Is 0.01 to 5% by weight.

  Examples of the moisturizing component include amino acids such as alanine, serine, leucine, isoleucine, threonine, glycine, trimethylglycine, proline, hydroxyproline, glucosamine, and theanine; polyhydric alcohols such as glycerin; sugar alcohols such as sorbitol Phospholipids such as lecithin and hydrogenated lecithin; NMF-derived components such as lactic acid, sodium pyrrolidonecarboxylate, and urea; plant-derived components such as lavender oil and red ginseng extract. When the moisturizing component is blended, the amount used can be appropriately selected in consideration of the feeling of use and effects on the skin, but it is, for example, 0.1 to 10% by weight, preferably, based on the total composition for external use of the present invention. 0.5 to 5% by weight.

  Examples of the keratin soft component include lanolin, urea, phytic acid, lactic acid, lactate, glycolic acid, salicylic acid, malic acid, citric acid, and the like. When the keratin soft component is blended, the amount used can be appropriately selected in consideration of the feeling of use and effects on the skin, but for example 0.0001 to 50% by weight relative to the total composition for external use of the present invention, Preferably it is 0.001 to 50 weight%, More preferably, it is 0.05 to 25 weight%.

  Examples of the blood circulation promoting component include plants (e.g., ginseng, ashitaba, arnica, ginkgo, fennel, entomop, dutch oak, chamomile, roman chamomile, carrot, gentian, burdock, rice, hawthorn, shitake, hawthorn, cherries, Senkyu, assembly, thyme, clove, chimpi, spruce, spruce, spruce, carrot, garlic, butcher bloom, grapes, buttons, maronier, melissa, yuzu, yokuinin, rosemary, rosehip, chimpi, spruce, spruce, peach, apricot , Walnuts, corn); tocopherol nicotinate, glucosyl hesperidin, hesperidin. When the blood circulation promoting component is blended, the amount used can be appropriately selected in consideration of the feeling of use and effects on the skin, but is preferably, for example, 0.00001 to 10% by weight, preferably based on the total composition for external use of the present invention. Is 0.0001 to 5 wt%, more preferably 0.001 to 5 wt%. The amount used in the case of using a plant-derived component is 0.00001 to 20% by weight, preferably 0.0001 to 15% by weight, and more preferably 0, in terms of an extract such as an extract, based on the whole composition for external use. 0.001 to 10% by weight.

  Examples of the sebum adsorbing component include talc, mica, hydroxyapatite, zinc oxide, aluminum silicate, and the like. Of these, mica, hydroxyapatite, and zinc oxide are preferable, and mica is particularly preferable. When the sebum adsorbing component is blended, the amount used can be appropriately selected in consideration of the feeling of use and effects on the skin, but for example, 0.001 to 35% by weight, preferably with respect to the total composition for external use of the present invention. Is 0.1 to 25% by weight.

  Examples of the hair-restoring ingredients include procyanidins, dipotassium glycyrrhizinate, capronium chloride, cephalanthin, menthol, hinokitiol, L-hydroxyproline, acetylhydroxyproline, fucoidan, capsicum tincture, cephalanthin, sultianin, symphunginicin, flavonosteroid, minoxidil, FGF 10, Enmiso extract (extract), assembly extract (extract), beetle extract (extract), amachazuru extract (extract), hypericum extract (extract), gentian extract (extract), sage extract (extract) , Peppermint extract (extract), hop extract (extract), yokuinin extract (extract), persimmon leaf extract (extract), ginger extract (extract), carrot extract (extract), bo Schima wallichii extract (extract), moutan bark extract (extract), and the like Jiyu extract (extract).

  In addition to the above-described components, the composition for external use of the present invention may be appropriately mixed with components usually used in the fields of pharmaceuticals, quasi drugs, cosmetics, etc., depending on the use or dosage form. . The ingredients that can be blended are not particularly limited, but for example, additives such as surfactants, preservatives, pH adjusters, chelating agents, stabilizers, irritation reducers, colorants, dispersants, fragrances, etc. Can do. In addition, these components can be mix | blended individually by 1 type or in combination of 2 or more types. Moreover, these usage-amounts can be suitably determined in the range which does not impair the effect of this invention from a conventionally well-known range.

  Examples of the surfactant include sorbitan esters such as sorbitan stearate, PEG sorbitan stearate, sorbitan monooleate, sorbitan monoisostearate and sorbitan monolaurate; POE-sorbitan monooleate; polyoxyethylene cured castor Oil (HCO-10); glycerin fatty acid esters such as glycerin monooleate, glycerin monostearate, and glycerin monomyristate; glycerin alkyl ethers such as monoisostearyl glyceryl ether and monomyristyl glyceryl ether; stearic acid polyglyceride, isostearin Polyglyceryl-10, diglyceryl monostearate, decaglyceryl decastearate, decaglyceryl decaisostearate, and diglyceride Various nonionic surfactants such as polyglycerin fatty acid esters such as rildiisostearate: or naturally derived surfactants such as lecithin, hydrogenated lecithin, saponin, surfactin sodium, cholesterol, bile acids, etc. Can do.

  Examples of the preservative include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and paraoxybenzoic acid. Examples include benzyl, methyl paraoxybenzoate, and phenoxyethanol.

  Examples of the pH adjuster include inorganic acids (hydrochloric acid, sulfuric acid, etc.), organic acids (lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, sodium succinate, etc.), inorganic bases (potassium hydroxide, water, etc.). Sodium oxide), organic bases (triethanolamine, diisopropanolamine, triisopropanolamine, etc.).

  Examples of the chelating agent include ethylenediaminetetraacetic acid (edetic acid), ethylenediaminetetraacetate (sodium salt (sodium edetate: Japanese Pharmacopoeia, EDTA-2Na, etc.), potassium salt, etc.), phytic acid, gluconic acid, polyphosphorus An acid, metaphosphoric acid, etc. are mentioned. Of these, sodium edetate is preferable.

  Examples of the stabilizer include magnesium sulfate, sodium polyacrylate, dibutylhydroxytoluene, butylhydroxyanisole and the like.

  Examples of the irritation reducing agent include licorice extract, gum arabic, polyvinylpyrrolidone, sodium alginate and the like.

  Examples of the colorant include inorganic pigments and natural pigments.

  Examples of the dispersant include sodium pyrophosphate, sodium hexametaphosphate, polyvinyl alcohol, polyvinyl pyrrolidone, methyl vinyl ether / maleic anhydride crosslinked copolymer, and organic acid.

[pH]
The composition for external use of the present invention may usually have a liquidity of pH 2.0 to 9.0, but preferably has a pH of 3.0 from the viewpoint of low irritation to skin and mucous membranes and good skin feeling. It is -8.5, More preferably, it is pH 3.5-8.0.

[Property / Formulation]
The property of the composition for external use of the present invention is not particularly limited, and may be liquid, fluid, or semi-solid. Examples of the preparation form include liquids, suspensions, emulsions, creams, emulsions, ointments, gels, liniments, lotions, and sheets obtained by impregnating a nonwoven fabric with a chemical. . Of these, emulsions, creams, emulsions, ointments, gels, and lotions are preferred, and creams, emulsions, ointments, and gels are particularly preferred.

  In addition, as a container filled with the external composition of this invention, a well-known container can be used without a restriction | limiting. The material of the container is not particularly limited. For example, the container can be provided by filling a container made of a material such as polyethylene terephthalate, polyethylene naphthalate, polyarylate, polycarbonate, polyethylene, or polypropylene, or glass. As the container, a container made of polyethylene terephthalate, polyethylene naphthalate, or polyarylate is particularly preferable.

<Method for producing composition for external use>
The manufacturing method in particular of the composition for external use of this invention is not restrict | limited, It can manufacture by selecting (A) component, the arbitrary component mentioned above, and another component suitably, and mixing in a solvent. For example, in order to obtain a gel-like composition, it is necessary to heat the mixture once to 60 ° C. to 95 ° C. and then leave it at room temperature or the like.

  The composition for external use of the present invention has an excellent collagen production promoting effect and cell activation effect, and can suppress, improve, and prevent wrinkles, tarmi and the like accompanying aging, and has an unprecedented new composition. It is. Moreover, the composition for external use of this invention can suppress, improve, and prevent the fall of the elasticity and elasticity of skin. Furthermore, since the component (A) also has an action as a gelling agent, the composition for external use of the present invention can be in an appropriate form as necessary. Because of such characteristics, the external composition of the present invention is an anti-aging external composition, an external composition for promoting collagen production and cell utilization, and an external composition for anti-wrinkle and tarmi. It can be suitably used in the quasi-drug and pharmaceutical fields.

<Collagen production promoter>
The collagen production promoter of this invention contains the lipid peptide represented by the said Formula (1), or its pharmaceutically acceptable salt ((A) component). The collagen production promoter of the present invention is used as an external composition for collagen production by arbitrarily blending components that are usually used in cosmetics, quasi-drugs, pharmaceuticals, etc., as long as the collagen production promotion effect is not impaired. be able to. The collagen production promoter of the present invention can also be used effectively as a composition for preventing or treating joint disorders, a composition for preventing or treating inflammatory diseases, and the like. The description of the component (A) in the external composition of the present invention can be applied to the description of the component (A) contained in the collagen production promoter of the present invention. Moreover, the collagen production promoter of this invention can be manufactured by mix | blending (A) component and another component in accordance with a conventional method. The collagen production promoter of the present invention can suppress / prevent / improve wrinkles, talmi, etc. associated with aging, cosmetics for aging care, quasi-drugs and pharmaceuticals, joint disorders, inflammatory diseases, etc. It can be used widely and suitably for medicaments for the prevention or treatment of.

<Cell activator>
The cell activator of the present invention comprises the lipid peptide represented by the formula (1) or a pharmaceutically acceptable salt thereof (component (A)). The cell activator of this invention can mix | blend suitably the component normally used for cosmetics, a quasi-drug, a pharmaceutical, etc. suitably in the range which does not impair the effect of this invention. The description of the component (A) in the composition for external use of the present invention can be applied to the description of the component (A) contained in the cell activator of the present invention. Moreover, the cell activator of this invention can be manufactured by mix | blending (A) component and another component in accordance with a conventional method. The cell activator of the present invention can suppress / prevent / improve wrinkles, talmi and the like accompanying aging, and can be widely and suitably used for aging care cosmetics, quasi drugs and pharmaceuticals.

<Cosmetics>
The cosmetic of the present invention has a collagen production promoting effect and a cell activation effect. Therefore, it can be widely and suitably used as a cosmetic for suppressing / preventing / improving wrinkles, tarmi and the like accompanying aging and a cosmetic for aging care.

<Quasi-drugs and pharmaceuticals>
The quasi drug / pharmaceutical of the present invention contains the collagen production promoter or cell activator of the present invention. Therefore, the quasi-drug / pharmaceutical of the present invention is excellent in collagen production promoting effect or cell activation effect, and can be suitably used as an external preparation. It can also be used effectively as a medicament for preventing or treating joint disorders, a medicament for preventing or treating inflammatory diseases, and the like.

<Collagen production promotion method>
The present invention also includes a method for promoting collagen production using the component (A) that is excellent in the collagen production promoting effect. For example, collagen production in cells constituting the skin can be promoted by using a composition for external use, cosmetics and pharmaceuticals containing the component (A). Thereby, suppression, prevention, and improvement of wrinkles, tarmi, etc. accompanying aging can be realized.

Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.
[Preparation of composition for external use]
According to the formulations shown in Tables 1 and 2 below, compositions for external use (test preparations) for Examples and Comparative Examples were prepared by a conventional method. The unit of numerical values in each table is weight (%) unless otherwise specified. Each external composition was subjected to the following tests and evaluated.

[Test example]
<Collagen production test>
Collagen production tests were carried out according to the following methods using the compositions for external use of Comparative Examples and Examples prepared according to the formulations shown in Table 1 below.
Each external composition was subjected to a collagen production test as follows. Human normal skin-derived fibroblasts (NHDF) were cultured in 48-well culture plates. More specifically, the cells were seeded at a density of 1.0 × 10 ⁴ cells / well and cultured at 37 ° C. in an environment of 5% carbon dioxide gas and 95% air for 2 days. As a culture solution, 400 μl each of a medium containing 10% by weight of fetal bovine serum (FBS) in Dulbecco's Modified Eagle Medium (DMEM) was used. Subsequently, the medium was replaced with a culture medium to which a small amount of FBS was added, that is, a DMEM medium containing 0.5% FBS, and further cultured for 6 hours. Thereafter, the culture solution was removed, and the test samples shown in Table 1 below were replaced with 400 μl of 0.5% FBS-containing DMEM medium dissolved at the respective concentrations and cultured. On the other hand, 400 μl of 0.5% FBS-containing DMEM medium to which no test sample was added was used as a control. After culturing for 3 days, the culture solution is collected, and the concentration of type I collagen secreted in the culture solution is quantified by an enzyme-linked immunoassay (Anti-Human Procollagen type C-peptide EIA Kit; manufactured by Takara Bio Inc.). The quantitative value was calculated as the amount of collagen per cell. Based on this quantitative result, the amount of collagen in each test culture solution (external composition) was calculated with the amount of type I collagen in the control culture solution as 100%. The results are shown in Table 1 and FIG.

Ｐａｌ−ＧＨ ： Ｐａｌｍｉｔｏｙｌ Ｄｉｐｅｐｔｉｄｅ−１８（ＩＮＣＩ名）

Pal-GH: Palmitoyl Dipeptide-18 (INCI name)

  As shown in Table 1 and FIG. 1, the composition for external use of the Examples had an effect of promoting collagen production. From this, it is thought that the composition for external use of an Example has an anti-wrinkle effect.

<Proliferation promotion test of skin fibroblasts>
Using the compositions for external use of Comparative Examples and Examples prepared according to the formulation described in Table 2 below, a skin fibroblast proliferation promotion test was performed according to the following method.
Human normal skin-derived fibroblasts (NHDF; CRL-2089) were cultured in 96-well culture plates. More specifically, the cells were seeded at a density of 1.0 × 10 ⁴ cells / well and cultured at 37 ° C. in an environment of 5% carbon dioxide gas and 95% air for 24 hours. As a culture solution, a medium containing 10% by weight of fetal bovine serum (FBS) in Dulbecco's Modified Eagle Medium (DMEM) was used in an amount of 100 μl per well. Thereafter, the culture solution was removed, and the test samples shown in the following table were replaced with 100 μl of serum-free medium dissolved at each concentration and cultured. Moreover, what added 100 microliters of serum-free culture media which do not add a test sample was used as control. After further culturing for 24 hours, the number of viable cells in each well was measured by the NR (Neutral Red) method. Based on the measurement results, the percentage of the number of living cells in each test sample addition group when the number of living cells in the control was 100% was defined as the cell growth rate (%). The results are shown in Table 2 and FIG.

Ｐａｌ−ＧＨ ： Ｐａｌｍｉｔｏｙｌ Ｄｉｐｅｐｔｉｄｅ−１８（ＩＮＣＩ名）

Pal-GH: Palmitoyl Dipeptide-18 (INCI name)

  As shown in Table 2 and FIG. 2, the compositions for external use of Examples had a skin fibroblast proliferation promoting effect (cell activation effect).

  A skin external preparation (formulation examples 1 to 13) having the following composition was prepared by a conventional method.

  Formulation Example 1: Whitening serum

  Formulation example 2: Whitening milky lotion

  Formulation Example 3: Whitening Cream

  Formulation Example 4: Spray cosmetic

  Formulation Example 5: Skin preparation

  Formulation Example 6: Sunscreen

  Formulation Example 7: Whitening emulsion

  Formulation Example 8: Whitening Cream

  Formulation Example 9: Whitening serum

  Formulation Example 10: Aging Care Cream

  Formulation Example 11: Aging Care Essence

  Formulation Example 12: Whitening serum

  Formulation Example 13: External hair restorer

Claims (6)

(A) The following formula (1)

(Wherein R ¹ is a saturated aliphatic group having 9 to 19 carbon atoms or an aliphatic group having one unsaturated bond. M is 0 or 1.) Or the external composition for anti-aging containing the pharmaceutically acceptable salt thereof.   The composition for external use according to claim 1, further comprising vitamin C.   The composition for external use according to claim 1 or 2, for suppressing, improving or preventing skin wrinkles or talmi.   The composition for external use of Claim 1 or 2 for suppressing, improving or preventing the fall of the elasticity and elasticity of skin.   The external composition of any one of Claims 1-4 for collagen production promotion. (A) The following formula (1)

(Wherein R ¹ is a saturated aliphatic group having 9 to 19 carbon atoms or an aliphatic group having one unsaturated bond. M is 0 or 1.) Or the collagen production promotion method using the pharmaceutically acceptable salt thereof.

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