Skin elasticity improving agents and topical skin preparations

Abstract

The objective is to provide a skin elasticity improving agent that can improve symptoms such as wrinkles, sagging, and loss of firmness in the skin by improving skin elasticity. [Solution] A skin elasticity improving agent containing one or both of tocopherol nicotinate and tocotrienol nicotinate as active ingredients.

Description

Technical Field

[0001] The present invention relates to a skin elasticity improver and a skin external preparation.

Background Art

[0002] Skin tissue is composed of cells such as epidermal cells and skin fibroblasts, and extracellular matrix (ECM) such as type I collagen, elastin, fibrillin-1, and tropoelastin. The extracellular matrix, also called the intercellular matrix, intercellular substance, or extracellular matrix, is a substance that fills the extracellular space and supports skin tissue. The production amount of the extracellular matrix (ECM) decreases due to factors such as ultraviolet rays, humidity, washing, stress, eating habits, and aging, resulting in a decrease in skin elasticity. And due to the decrease in skin elasticity, symptoms such as skin wrinkles, sagging, and loss of firmness appear.

[0003] So far, various methods have been studied to improve skin wrinkles, sagging, etc. For example, Patent Document 1 discloses a skin external preparation or cosmetic for improving wrinkles containing (a) niacinamide, (b) a polyphenol-containing plant extract such as soybean and sesame, and (c) an oil-soluble active ingredient such as vitamin E or its derivative. Also, Patent Document 2 discloses a method for improving wrinkles by massaging while applying a skin external preparation containing (A) niacinamide, (B) edelweiss extract, and (C) odoricoso extract to the face.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, Patent Document 1 improves wrinkles by increasing the skin's moisture content in addition to improving skin elasticity, and there is room for improvement from the perspective of improving skin elasticity. Furthermore, Patent Document 2 states that the effect is significantly reduced if the topical agent is not massaged while applied to the skin, but there is a need for an agent that can provide sufficient wrinkle improvement without relying on external factors such as massage, so that the effect can be obtained even if the user does not have massage skills.

[0006] The present invention aims to provide a skin elasticity improving agent that can improve symptoms such as wrinkles, sagging, and loss of firmness in the skin by improving skin elasticity. [Means for solving the problem]

[0007] The inventors of the present invention conducted diligent research to solve the above problems and, as a result, discovered that skin elasticity can be improved by using one or both of tocopherol nicotinate and tocotrienol nicotinate as active ingredients, thus completing the present invention. In other words, the present invention includes the following:

[0008] [1] A skin elasticity improving agent containing either or both tocopherol nicotinate and tocotrienol nicotinate as active ingredients. [2] The aforementioned improvement in skin elasticity is due to an increase in extracellular matrix-related gene expression and extracellular matrix A skin elasticity improving agent described in [1], which is due to the promotion of protein synthesis. [3] The skin elasticity improving agent according to [2], wherein the improvement in skin elasticity is further due to the promotion of fiber formation. [4] The skin elasticity improving agent according to [2] or [3], wherein the extracellular matrix-related gene is one or more selected from the group consisting of type I collagen gene, lysyl oxidase gene, fibrillin-1 gene, tropoelastin gene, and emylin-1 gene. [5] The skin elasticity improving agent according to [3], wherein the extracellular matrix protein is type I collagen and the fibers are type I collagen fibers. [6] A skin elasticity improving agent according to any one of [1] to [5], wherein the total content of tocopherol nicotinate and tocotrienol nicotinate is 85% by weight or more and 100% by weight or less. [7] A topical skin preparation for improving skin elasticity, containing a skin elasticity improving agent as described in any of [1] to [6]. [8] A cosmetic composition or a pharmacopoeia for external use, as described in [7]. [9] A method for improving skin elasticity, comprising the step of applying a topical skin preparation described in [7] or [8] to the skin surface. [Effects of the Invention]

[0009] According to the present invention, a skin elasticity improving agent can be provided that can improve symptoms such as wrinkles, sagging, and loss of firmness of the skin by improving skin elasticity. Preferably, the present invention can provide a topical skin preparation for improving skin elasticity. [Brief explanation of the drawing]

[0010] [Figure 1] This graph shows the relative expression levels of type I collagen mRNA in the evaluation of ECM-related gene expression in Examples 1 and 2 and Comparative Examples 1 to 3. [Figure 2] This graph shows the relative expression levels of lysyl oxidase mRNA in the evaluation of ECM-related gene expression in Examples 1 and 2 and Comparative Examples 1 to 3. [Figure 3]It is a graph showing the expression level (relative value) of fibrillin-1 mRNA in the evaluation of ECM-related gene expression in Examples 1 and 2 and Comparative Examples 1 to 3. [Figure 4] It is a graph showing the expression level (relative value) of tropoelastin mRNA in the evaluation of ECM-related gene expression in Examples 1 and 2 and Comparative Examples 1 to 3. [Figure 5] It is a graph showing the expression level (relative value) of emilin-1 mRNA in the evaluation of ECM-related gene expression in Examples 1 and 2 and Comparative Examples 1 to 3. [Figure 6] It is a graph showing the amount of type I collagen in the evaluation of promotion of type I collagen synthesis in Examples 3-1 to 3-6 and Comparative Examples 4 and 5-1 to 5-5. [Figure 7] It is a graph showing the amount of type I collagen in the evaluation of promotion of type I collagen synthesis in Examples 4-1 to 4-6 and Comparative Examples 6 and 7-1 to 7-5. [Figure 8] It is a fluorescence staining image of type I collagen fibers (photograph substituting for drawing) in the evaluation of promotion of type I collagen fiber formation in Example 5 and Comparative Examples 8 to 10. [Figure 9] It is a graph showing the amount (relative value) of type I collagen fiber bundles in the evaluation of promotion of type I collagen fiber formation in Example 5 and Comparative Examples 8 to 10. [Figure 10] It is a fluorescence staining image of elastic fibers (photograph substituting for drawing) in the evaluation of promotion of elastic fiber formation in Example 6 and Comparative Examples 11 to 13.

Modes for Carrying Out the Invention

[0011] Hereinafter, embodiments of the present invention will be described in detail. The description of the constituent elements described below is an example (representative example) of the embodiments of the present invention, and the present invention is not specifically limited to these contents as long as it does not exceed the gist thereof.

[0012] 1. Skin elasticity improver A first embodiment of the present invention is a skin elasticity improving agent containing one or both of tocopherol nicotinate and tocotrienol nicotinate as active ingredients. The skin elasticity improving agent according to this embodiment can improve symptoms such as wrinkles, sagging, and loss of firmness of the skin by exhibiting its skin elasticity improving effect. In this specification, skin elasticity improvement is a concept that includes both maintaining and improving skin elasticity. Furthermore, improvement of symptoms such as wrinkles, sagging, and loss of firmness of the skin is a concept that includes alleviation and cure of such symptoms. The target population for skin elasticity improving agents is not particularly limited, as long as improvement in skin elasticity is desired, for example, mammals, specifically humans. There are no restrictions on the age, sex, etc. of the target population.

[0013] 1-1. Active Ingredients The active ingredient of the skin elasticity improving agent according to this embodiment is either or both tocopherol nicotinate and tocotrienol nicotinate, preferably tocopherol nicotinate. When the active ingredient is both tocopherol nicotinate and tocotrienol nicotinate, any mixing ratio of these is arbitrary.

[0014] Tocopherol nicotinate is one or more selected from α-, β-, γ-, and δ-tocopherol nicotinate, and when two or more of these are used, the combination and ratio are arbitrary. Of these, α-tocopherol nicotinate is preferred from the viewpoint of ease of manufacture, availability, and skin elasticity improvement effect. Furthermore, tocopherol may be either the d-isomer (natural type) or the dl-isomer (synthetic type), but the dl-isomer is preferred from the viewpoint of ease of manufacture, availability, and skin elasticity improvement effect. In other words, a particularly preferred embodiment of tocopherol nicotinate is dl-α-tocopherol nicotinate.

[0015] The tocotrienol nicotinate is one or more selected α-, β-, γ-, and δ-tocotrienol nicotinate esters, and when two or more of these are used, the combination and ratio are arbitrary. Of these, from the viewpoint of ease of manufacture, availability, and skin elasticity improvement effect, the tocotrienol nicotinate ester is preferably α-tocotrienol nicotinate ester. Furthermore, the tocotrienol may be either the d-isomer (natural type) or the dl-isomer (synthetic type), but from the viewpoint of ease of manufacture, availability, and skin elasticity improvement effect, the dl-isomer is preferred. That is, a particularly preferred embodiment of the tocotrienol nicotinate ester is dl-α-tocotrienol nicotinate ester.

[0016] The tocopherol nicotinate and tocotrienol nicotinate used in this embodiment are either known or can be easily produced by methods similar to known manufacturing methods. Furthermore, commercially available products may be used as tocopherol nicotinate and tocotrienol nicotinate.

[0017] In the skin elasticity improving agent according to this embodiment, the content of the active ingredients tocopherol nicotinate and tocotrienol nicotinate is not particularly limited, but from the viewpoint of ensuring a sufficient skin elasticity improving effect, it is usually 85% by weight or more, preferably 90% by weight or more, and more preferably 95% by weight or more. Furthermore, the content of the active ingredients in the skin elasticity improving agent is The limit is not particularly limited, and is usually 100% by weight or less, but may be 99% by weight or less or 98% by weight or less.

[0018] Based on the results of the examples described later, the inventors of this invention surmise the following mechanism by which the active ingredient exerts its skin elasticity-improving effect.

[0019] The active ingredients in this embodiment, tocopherol nicotinate and / or tocotrienol nicotinate, increase the expression of extracellular matrix (ECM)-related genes and promote the synthesis of ECM proteins. Preferred ECM-related genes whose expression is increased by the skin elasticity improving agent include, but are not limited to, type I collagen genes, lysyl oxidase genes, fibrin-1 genes, tropoelastin genes, and emilin-1 genes. Furthermore, preferred ECM proteins whose synthesis is promoted by the skin elasticity improving agent include, but are not limited to, one or more selected from the group consisting of type I collagen, lysyl oxidase, fibrin-1, tropoelastin, and emilin-1.

[0020] As a method for evaluating the increased expression of ECM-related genes, as shown in the examples described later, a method can be employed in which the skin elasticity improving agent according to this embodiment is added to a skin model such as normal human dermal fibroblasts (NHDF), cultured for about 24 or 48 hours, and then the expression levels of ECM mRNA such as type I collagen mRNA and lysyl oxidase mRNA are measured by real-time PCR (RT-PCR) using, for example, the StepOne Real-Time PCR System (Thermo Fisher Scientific).

[0021] As a method for evaluating the promotion of ECM protein synthesis, as shown in the examples described later, a method can be employed in which the skin elasticity improving agent according to this embodiment is added to a skin model such as normal human dermal fibroblasts (NHDF), cultured for about 24 or 48 hours, and then the amount of ECM protein is measured by ELISA.

[0022] Furthermore, the active ingredient in this embodiment not only promotes the synthesis of ECM proteins, but preferably also promotes fiber formation from ECM proteins. Examples of fibers whose formation is promoted include collagen fibers and elastic fibers mainly composed of fibrillin-1, and the active ingredient in this embodiment is particularly effective in promoting the formation of type I collagen fibers. In this specification, the concept of promoting fiber formation includes promoting the formation of fibers themselves, increasing the size of individual fibers to promote the formation of thicker and longer fibers, and promoting the density of fibers to promote the formation of thick fiber bundles.

[0023] In other words, in this embodiment, first, the skin elasticity improving agent promotes the synthesis of ECM proteins, increasing the amount of type I collagen, which is the raw material for type I collagen fibers; fibrillin-1, tropoelastin, emylin-1, etc., which are the raw materials for elastic fibers; and lysyl oxidase, an enzyme that cross-links these fibers, in the skin cells. Preferably, the skin elasticity improving agent ensures that there is a sufficient amount of ECM proteins, which are the raw materials for type I collagen fibers and / or elastic fibers, as well as cross-linking enzymes, in the skin cells, thereby promoting the formation of type I collagen fibers and / or elastic fibers. As a result, fiber formation proceeds predominantly, and a high skin elasticity improvement effect is obtained.

[0024] As a method for evaluating the promotion of fibrous formation, as shown in the examples described later, a method can be employed in which the skin elasticity improving agent according to this embodiment is added to a skin model such as normal human dermal fibroblasts (NHDF), cultured for about 7 days, and then tissue sections of the skin model are stained by immunofluorescence staining and observed with a fluorescence microscope. In the fluorescence stained image obtained by fluorescence microscopy observation, the results can be compared with those obtained when the skin model was cultured without the skin elasticity improving agent (control). If the number of fibers, fiber size, fiber bundle size, etc., increase compared to the previous state, it is considered that fiber formation has been promoted. In addition, the amount of fiber bundles can be quantified and evaluated using image processing software based on the fluorescence intensity of the fluorescent stained image.

[0025] Thus, the skin elasticity enhancer according to this embodiment exhibits a skin elasticity improvement effect by promoting ECM protein synthesis, preferably by promoting the expression of ECM-related genes, thereby promoting fiber formation from increased ECM proteins. Therefore, the skin elasticity enhancer according to this embodiment can also be described in terms of its effect as an ECM-related gene expression enhancer, an ECM protein synthesis enhancer, or an ECM protein synthesis and fiber formation enhancer.

[0026] 1-2. Other ingredients The skin elasticity improving agent according to this embodiment may contain other components as needed, as long as they do not hinder the effects of the present invention. Other ingredients include known wrinkle-improving agents such as nicotinamide and vitamin E, as well as known excipients, fragrances, colorants, emulsifiers, stabilizers, thickeners, enzymes, preservatives, lubricants, surfactants, binders, absorption enhancers, adsorbents, humectants, solubilizers, and preservatives. Furthermore, if the skin elasticity improving agent according to this embodiment contains other components, the amount thereof is not particularly limited, but may be 1% by weight or more or 2% by weight or more, and is usually 15% by weight or less, preferably 10% by weight or less, and more preferably 5% by weight or less.

[0027] 1-3. Method for manufacturing a skin elasticity improving agent The method for producing the skin elasticity improving agent according to this embodiment is not particularly limited and can be produced by mixing the active ingredient and other ingredients in a known manner. In this case, the order in which the ingredients are mixed is not particularly limited and all ingredients may be mixed at once or in any order. Alternatively, if no other ingredients are added to the skin elasticity improving agent, commercially available tocopherol nicotinate, tocotrienol nicotinate, or mixtures thereof can be used as is as a skin elasticity improving agent.

[0028] 2. Topical skin preparations A second embodiment of the present invention is a topical skin preparation for improving skin elasticity, comprising a skin elasticity improving agent according to the first embodiment of the present invention. Based on the effects of the skin elasticity improving agent, the topical skin preparation of this embodiment can improve symptoms such as wrinkles, sagging, and loss of firmness of the skin.

[0029] The amount of skin elasticity improving agent in a topical skin preparation is not particularly limited, but from the viewpoint of ensuring a sufficient skin elasticity improving effect, it is usually 0.001% by weight or more, preferably 0.1% by weight or more, and more preferably 1% by weight or more. From the viewpoint of preventing excessive coloring, odor, etc., it is usually 35% by weight or less, preferably 30% by weight or less, and more preferably 25% by weight or less.

[0030] Preferred examples of topical skin preparations include cosmetic compositions and pharmaceutical topical compositions. The specific embodiments of the topical skin preparation according to this embodiment will be described below, specifically for cases where the preparation is a cosmetic composition and a pharmaceutical topical composition.

[0031] 2-1. Cosmetic Compositions The topical skin preparation according to this embodiment can be made into a cosmetic composition by mixing the skin elasticity improving agent according to the first embodiment of the present invention with a base or carrier commonly used in cosmetics, and additives as needed.

[0032] 2-1-1. Substrate or carrier The base or carrier may include hydrocarbons such as liquid paraffin, squalane, gelling hydrocarbons (such as Plastibase), ozokerite, α-olefin oligomers, and light liquid paraffin; methylpolysiloxane, cross-linked methylpolysiloxane, highly polymerized methylpolysiloxane, cyclic silicone, alkyl-modified silicone, cross-linked alkyl-modified silicone, amino-modified silicone, polyether-modified silicone, polyglycerin-modified silicone, cross-linked polyether-modified silicone, cross-linked alkyl polyether-modified silicone, silicone-alkyl chain-comodified polyether-modified silicone, silicone-alkyl chain-comodified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicone, phenyl-modified silicone, and silicone resins; cellulose derivatives such as ethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose; polyvinylpyrrolidone; carrageenan; polyvinyl butyrate; and polyethylene glycol. Examples include: dioxane; butylene glycol adipic acid polyester; esters such as isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, pentaerythritol tetra-2-ethylhexanoate, and triethylhexanoin; polysaccharides such as dextrin and maltodextrin; lower alcohols such as ethanol and isopropanol; glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether; polyhydric alcohols such as polyethylene glycol, propylene glycol, 1,3-butylene glycol, glycerin, and isoprene glycol; and aqueous bases such as water. The base or carrier can be used individually or in any combination and ratio of two or more types.

[0033] 2-1-2. Additives The cosmetic composition may contain known additives added to cosmetics, such as surfactants, thickeners, pH adjusters, chelating agents, stabilizers, irritation reducers, preservatives, colorants, dispersants, fragrances, pearlescent agents, etc., to the extent that they do not impair the effects of the present invention. Additives can be used individually or in any combination and ratio of two or more.

[0034] Examples of surfactants include sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan diglycerol penta-2-ethylhexyl sorbitan, and sorbitan tetra-2-ethylhexyl diglycerol sorbitan; propylene glycol fatty acid esters such as propylene glycol monostearate; hydrogenated castor oil derivatives such as polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (HCO-60), and polyoxyethylene hydrogenated castor oil 80; and polyoxyethylene (20) monolauryl sorbitan. Examples include polyoxyethylene sorbitan fatty acid esters such as sorbitan (polysorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate 80), and polyoxyethylene (20) sorbitan isostearate; polyoxyethylene monococonut oil fatty acid glyceryl; glycerin alkyl ethers; alkyl glucosides; polyoxyalkylene alkyl ethers such as polyoxyethylene cetyl ether; amines such as stearylamine and oleylamine; silicone-based surfactants such as polyoxyethylene methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone; and others.

[0035] Examples of thickening agents include guar gum, locust bean gum, carrageenan, and xanthan gum. Examples of additives include xanthan gum, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, alkyl acrylate methacrylate copolymer, polyethylene glycol, bentonite, (hydroxyethyl acrylate / sodium acryloyldimethyltaurate) copolymer, (ammonium acryloyldimethyltaurate / vinylpyrrolidone) copolymer, etc. Of these, preferred additives are xanthan gum, alkyl acrylate methacrylate copolymer, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyethylene glycol, carboxyvinyl polymer, (hydroxyethyl acrylate / sodium acryloyldimethyltaurate) copolymer, and (ammonium acryloyldimethyltaurate / vinylpyrrolidone) copolymer.

[0036] Examples of pH adjusters include inorganic acids such as hydrochloric acid and sulfuric acid; organic acids such as lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, and sodium succinate; organic acids such as potassium hydroxide and sodium hydroxide; and organic bases such as triethanolamine, diisopropanolamine, and triisopropanolamine.

[0037] Examples of chelating agents include EDTA, NTA, DTPA, GLDA, HEDTA, GEDTA, TTHA, HIDA, and DHEG.

[0038] Examples of stabilizers include sodium polyacrylate, dibutylhydroxytoluene, and butylhydroxyanisole.

[0039] Examples of irritation-reducing agents include licorice extract and sodium alginate.

[0040] Examples of preservatives include para-hydroxybenzoic acid esters such as methylparaben, ethylparaben, propylparaben, and butylparaben, as well as benzoin, sodium dehydroacetate, hinokitiol, and phenoxyethanol.

[0041] Examples of colorants include inorganic pigments and natural dyes.

[0042] Examples of dispersants include glyceryl stearate, glyceryl oleate, sorbitan stearate, sorbitan oleate, polyoxyethylene alkyl ethers, polyethylene glycol fatty acid esters, and sorbitan fatty acid esters.

[0043] Examples of fragrances include natural fragrances and synthetic fragrances.

[0044] Examples of pearlescent luster imparting agents include ethylene glycol distearate, ethylene glycol monostearate, and triethylene glycol distearate.

[0045] 2-1-3. Other active ingredients The cosmetic composition may contain other active ingredients, to the extent that they do not impair the effects of the present invention. These other active ingredients may overlap with other ingredients in the skin elasticity improving agent according to the first embodiment of the present invention.

[0046] Other specific examples of active ingredients include those commonly used in cosmetics, such as antioxidants; anti-aging ingredients; anti-inflammatory ingredients; whitening ingredients; cell-activating ingredients; vitamins; blood circulation promoting ingredients; moisturizing ingredients; ingredients that prevent and / or repair DNA damage; anti-glycation ingredients; peptides or their derivatives; amino acids or their derivatives; hydroquinone glycosides or their esters; etc. Other active ingredients can be used individually or in any combination of two or more. It can be used in combination and in ratio.

[0047] Antioxidant components include those derived from plants (e.g., grapes, ginseng, comfrey, etc.); proanthocyanidins; ascorbic acid and its derivatives; glucosyl hesperidin; ergothioneine; sodium bisulfite; superoxide dismutase; hypotaurine; astaxanthin; tocopherol or its derivatives; dibutylhydroxytoluene; and others.

[0048] Examples of anti-aging ingredients include hydrolyzed soy protein, kinetin, nicotinamide, retinol, retinoic acid, retinal, or retinoids such as their derivatives.

[0049] Examples of anti-inflammatory components include those derived from plants (e.g., comfrey); allantoin; glycyrrhizic acid or its derivatives; zinc oxide; pyridoxine hydrochloride; tocopherol acetate; salicylic acid or its derivatives; ε-aminocaproic acid; and others.

[0050] Examples of whitening ingredients include ascorbic acid or its derivatives; hydroquinone or its derivatives; kojic acid; ellagic acid; phytic acid; butylresorcinol; pantothenic acid or its derivatives; tranexamic acid; cysteine; vitamin E or its derivatives such as tocopherol and tocotrienol; and plant-derived ingredients with whitening properties (e.g., plant extracts).

[0051] Examples of cell-activating components include those derived from plants (e.g., bilberry); amino acids such as ε-aminocaproic acid; vitamins such as thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acid; α-hydroxy acids such as glycolic acid and lactic acid; flavonoids; allantoin; retinol acetate; retinol palmitate; and others.

[0052] Examples of vitamins include vitamin B2s such as riboflavin, flavin adenine dinucleotide, and riboflavin sodium phosphate; nicotinic acids such as nicotinamide; vitamin Cs (ascorbic acid or its derivatives) such as sodium ascorbate phosphate, magnesium ascorbate phosphate, ascorbate glucoside, tetra-2-hexyldecanoate ascorbyl, ascorbate palmitate, calcium ascorbate, and sodium ascorbate; vitamin B1s such as thiamine hydrochloride, thiamine nitrate, benfotiamine, fursultiamine hydrochloride, and bisbentiamine; vitamin B6s such as pyridoxine hydrochloride and pyridoxal; vitamin B12s such as cyanocobalamin, mecobalamin, and hydroxocobalamin; folic acids such as folic acid; pantothenic acids such as pantothenic acid, calcium pantothenate, and pantothenyl alcohol (panthenol); and biotins such as biotin and biocitin. In addition, other vitamin-like factors such as carnitine, ferulic acid, orotic acid, and γ-oryzanol may be used as substitutes for vitamins.

[0053] Examples of blood circulation-promoting ingredients include those derived from plants (e.g., ginseng, angelica tree, arnica, ginkgo, fennel, laurel, watercress, chamomile, Roman chamomile, carrot, gentian, burdock, rice, hawthorn, shiitake mushroom, hawthorn, juniper, cinnamon, gentian, thyme, clove, dried tangerine peel, angelica, peach kernel, spruce, carrot, garlic, butcher's broom, grape, peony, horse chestnut, lemon balm, yuzu, coix seed, rosemary, rosehip, peach, apricot, walnut, corn); glucosyl hesperidin; and others.

[0054] Moisturizing ingredients include those derived from plants (e.g., cogongrass); alanine, serine, and royl monoxide. Amino acids or their derivatives such as cin, isoleucine, threonine, glycine, proline, hydroxyproline, glucosamine, and theanine; proteins, peptides or their hydrolysates such as collagen, gelatin, and elastin; polyhydric alcohols such as glycerin, 1,3-butylene glycol, propylene glycol, polyethylene glycol, dipropylene glycol, and diglycerin; sugar alcohols such as sorbitol; phospholipids such as lecithin and hydrogenated lecithin; hyaluronic acid (high molecular weight or natural type; the same applies to moisturizing ingredients below), sodium hyaluronate, hydrolyzed hyaluronic acid, cationized hyaluronic acid, acetylated hyaluronic acid, or salts thereof; mucopolysaccharides such as heparin and chondroitin; NMF-derived components such as lactic acid, sodium pyrrolidone carboxylate, and urea; polyglutamic acid; MPC polymer (e.g., LIPID Examples include polymers having phospholipid polar groups such as URE (registered trademark), polyoxypropylene methyl glucoside, trimethylglycine (betaine), hydroxyethyl urea, acrylic acid / acrylamide / dimethyldiallylammonium chloride copolymer, sorbitol, etc.

[0055] Components that have a preventive and / or repair effect on DNA damage include components derived from animals (e.g., Artemia); components derived from plants (e.g., cat's claw); nucleic acid components such as DNA, DNA salts, RNA, and RNA salts; and so on.

[0056] Examples of anti-glycation components include plant extracts (e.g., Budreja axillaris leaf extract; evening primrose extract; Amla fruit, juice, or extracts thereof) (Japanese Patent Publication No. 2006-028090, Japanese Patent Publication No. 2006-62989, etc.); l-arginine, l-lysine, hydrolyzed casein (Japanese Patent Publication No. 2001-039816); hydrolyzable tannins (Japanese Patent Publication No. Hei 9-40519); carnosine ("Latest Skin Diagnostic Manual for Beauty," Fragrance Journal Co., Ltd., published August 15, 2006); and others.

[0057] Examples of peptides or their derivatives include keratin-degrading peptides, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin-degrading peptides, collagen-degrading peptides, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin-degrading peptides, conchiolin-degrading peptides, hydrolyzed conchiolin, silk protein-degrading peptides, hydrolyzed silk, sodium lauroyl hydrolyzed silk, soy protein-degrading peptides, hydrolyzed soy protein, wheat protein, wheat protein-degrading peptides, hydrolyzed wheat protein, casein-degrading peptides, and acylated peptides (such as palmitoyl oligopeptides, palmitoyl pentapeptides, and palmitoyl tetrapeptides).

[0058] Examples of amino acids or their derivatives include betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine, leucine, isoleucine, valine, histidine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosine, and creatine.

[0059] Examples of hydroquinone glycosides or their esters include α-arbutin, arbutin, and its esters.

[0060] 2-1-4. Forms of cosmetic compositions The form of the cosmetic composition is not particularly limited, but in terms of function, examples include basic cosmetics such as lotions, emulsions, creams, serums, sunscreens, masks, hand creams, body lotions, and body creams; cleansing cosmetics such as facial cleansers, makeup removers, and body shampoos; and makeup products such as foundations, makeup bases, lip balms, lipsticks, and blushes. Examples include cosmetic products such as quad cosmetics. Such cosmetic compositions can be manufactured according to conventional methods. These cosmetic compositions can also be sealed in containers such as bottles, bags, cans, spray cans, atomizers, and boxes.

[0061] 2-2. Compositions for external use of pharmaceuticals The topical skin preparation according to this embodiment can be mixed with a pharmaceutical active ingredient, a base or carrier commonly used in topical pharmaceutical compositions, and additives as needed to form a topical pharmaceutical composition. In this specification, "pharmaceutical" is a concept that includes both pharmaceuticals and quasi-drugs.

[0062] 2-2-1. Base or carrier The base or carrier may be a solvent such as water, physiological saline, isopropanol, concentrated glycerin, ethanol, propylene glycol, or macrogol 400; synthetic oils such as medium-chain triglycerides and hard fats; coconut oil, palm oil, palm kernel oil, safflower oil, olive oil, castor oil, avocado oil, sesame oil, tea oil, evening primrose oil, wheat germ oil, macadamia nut oil, hazelnut oil, kukui nut oil, rosehip oil, meadowfoam oil, peach kernel oil, tea tree oil, peppermint oil, corn oil, rapeseed oil, sunflower oil, wheat germ oil, linseed oil, cottonseed oil, soybean oil, peanut oil, rice bran oil, squalane, etc., or hydrogenated oils thereof; liquid paraffin (mineral oil), heavy liquid isoparaffin Examples include oily bases such as fins, light liquid isoparaffins, α-olefin oligomers, polyisobutene, hydrogenated polyisobutene, polybutene, squalane, olive-derived squalane, squalene, and triethylhexanoin; higher fatty acids such as isostearic acid, behenic acid, undecylenic acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, erucic acid, docosahexaenoic acid, eicosapentaenoic acid, isohexadecanoic acid, anteisohenicosanoic acid, long-chain branched fatty acids, dimer acids, or hydrogenated dimer acids; and polyhydric alcohols such as propylene glycol, polyethylene glycol, glycerin, 1,3-butylene glycol, isoprene glycol, and dipropylene glycol. The base or carrier can be used individually or in any combination and ratio of two or more types.

[0063] 2-2-2. Additives The topical pharmaceutical composition may contain known additives, such as suspending agents, thickeners, gelling agents, emulsifiers, etc., to the extent that they do not impair the effects of the present invention. Furthermore, the components exemplified as additives that may be included in the cosmetic composition can also be used. Additives may be used individually or in any combination and ratio of two or more.

[0064] Ingredients that can be used as suspending agents, thickeners, or gelling agents include gum arabic, aluminum monostearate, or water-soluble polymers [e.g., methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carmellose, carmellose sodium, carmellose calcium, povidone, carboxyvinyl polymer (Carbopol 941; manufactured by Noveon, Inc., etc.; also known as carbomer)].

[0065] Examples of emulsifiers include polyoxyl 40 stearate, sorbitan sesquioleate, polysorbate 80, sodium lauryl sulfate, lauromacrogol, acacia gum, cholesterol, stearic acid, glyceryl monostearate, povidone, polyglycerin fatty acid esters (e.g., "Ryoto Polyglycerides" manufactured by Mitsubishi Chemical Corporation), sucrose fatty acid esters (e.g., "Ryoto Sugar Esters" manufactured by Mitsubishi Chemical Corporation), sorbitan fatty acid esters, propylene glycol fatty acid esters, calcium stearoyl lactylate, soy lecithin, egg yolk lecithin, and polysorbate.

[0066] 2-2-3. Other active ingredients Furthermore, the topical pharmaceutical composition may contain other active ingredients, to the extent that they do not impair the effects of the present invention. Note that these other active ingredients may overlap with other components in the skin elasticity improving agent according to the first embodiment of the present invention. Other specific examples of active ingredients include those listed as other active ingredients that may be included in a cosmetic composition.

[0067] 2-2-4. Forms of topical pharmaceutical compositions The form of the topical pharmaceutical composition is not particularly limited and includes, for example, liquids, suspensions, emulsions, creams, ointments, gels, liniments, lotions, poultices, etc. These preparations can be manufactured in accordance with the methods described in the General Provisions of the 17th Revised Japanese Pharmacopoeia.

[0068] 2-3. Labeling of topical skin preparations for improving skin elasticity The topical skin preparation according to this embodiment may be sold with a label indicating that it is a topical skin preparation used to improve skin elasticity. For example, the label may be "for improving skin elasticity" or "intended to improve skin elasticity," or it may be a label based on the effects resulting from improved skin elasticity, such as "for wrinkle improvement," "for sagging improvement," or "for firmness improvement," or it may be a label relating to the mechanism of skin elasticity improvement, such as "for promoting ECM-related gene expression," "for promoting ECM synthesis," or "for promoting ECM synthesis and fiber formation."

[0069] 3. Methods for improving skin elasticity A third embodiment of the present invention is a method for improving skin elasticity, which includes an application step of applying a topical skin preparation according to the second embodiment of the present invention to the skin surface. The area to which the topical skin preparation is applied is not particularly limited, and examples include the face, neck, hands and feet, and body, with the face or neck being preferred. The amount and frequency of application of topical skin preparations should be appropriately selected according to skin condition, application area, age, weight, etc. For example, a standard dose is within the range of 1 mg of the active ingredient applied per day, and it is usually sufficient to apply it directly to the skin surface once a day or in several divided doses. The skin elasticity improvement method according to this embodiment may include, as necessary, optional steps such as a massage step or a steaming step, in addition to the application step. [Examples]

[0070] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples unless it exceeds the gist of the invention.

[0071] <Example 1: Evaluation of ECM-related gene expression> Tocopherol nicotinate (manufactured by Mitsubishi Chemical Corporation; dl-α-tocopherol nicotinate; hereinafter referred to as "EN") was used as a skin elasticity improving agent.

[0072] Normal human dermal fibroblasts (NHDF) are measured in 2.0 × 10⁻⁶ units. 4 Cells were seeded at a cell density of cells / well, and a 50 μM EN solution was added as a test sample. The cells were then cultured at 37°C for 24 hours. Total RNA was extracted from the cultured NHDF, and the expression levels of type I collagen mRNA, lysyl oxidase mRNA, fibrillin-1 mRNA, tropoelastin mRNA, and emylin-1 mRNA were measured using a real-time PCR instrument (StepOne Real-Time PCR System, Thermo Fisher Scientific). The expression levels of each mRNA were determined as relative values, with the mRNA expression level in the system without the addition of a skin elasticity improving agent (Comparative Example 1) set to 1.0. The results are shown in Table 1 and Figures 1-5.

[0073] <Example 2: Evaluation of ECM-related gene expression> The expression levels of each mRNA were determined in the same manner as in Example 1, except that the concentration of EN in the test sample was set to 100 μM. The results are shown in Table 1 and Figures 1-5.

[0074] <Comparative Example 1: Evaluation of ECM-related gene expression> The expression levels of each mRNA were determined in the same manner as in Example 1, except that the test sample containing a skin elasticity improving agent was not added (control). The results are shown in Table 1 and Figures 1-5.

[0075] <Comparative Example 2: Evaluation of ECM-related gene expression> Vitamin E (dl-α-tocopherol; hereinafter referred to as "VE") was used as a skin elasticity improving agent. The expression levels of each mRNA were determined in the same manner as in Example 1, except that a VE concentration of 100 μM solution was used as the test sample. The results are shown in Table 1 and Figures 1-5.

[0076] <Comparative Example 3: Evaluation of ECM-related gene expression> Nicotinic acid (hereinafter referred to as "NA") was used as a skin elasticity improving agent. The expression levels of each mRNA were determined in the same manner as in Example 1, except that a solution with an NA concentration of 100 μM was used as the test sample. The results are shown in Table 1 and Figures 1-5.

[0077] [Table 1]

[0078] Table 1 and Figures 1-5 show that in Examples 1 and 2, where a skin elasticity improving agent containing EN was applied, the expression of type I collagen mRNA, lysyl oxidase mRNA, fibrillin-1 mRNA, tropoelastin mRNA, and emylin-1 mRNA increased compared to the control (Comparative Example 1). In particular, the expression of type I collagen mRNA, lysyl oxidase mRNA, and fibrillin-1 mRNA increased with the increase in the concentration of EN in the test sample. Consequently, expression levels also increased, and it was confirmed that the expression levels of type I collagen mRNA and lysyl oxidase mRNA, in particular, increased significantly.

[0079] On the other hand, in Comparative Example 2, which used a skin elasticity improving agent containing VE, the expression levels of type I collagen mRNA and lysyl oxidase mRNA were similar to those of the control (Comparative Example 1). Although fibrillin-1 mRNA expression levels were higher than in the control group, the level of mRNA expression was not as high as in Examples 1 and 2. Furthermore, tropoelastin mRNA and emylin-1 mRNA expression levels were lower than in the control group.

[0080] In Comparative Example 3, which used a skin elasticity improving agent containing NA, it was found that the expression levels of type I collagen mRNA, lysyl oxidase mRNA, and tropoelastin mRNA were lower than in the control (Comparative Example 1). Although the expression level of tropoelastin mRNA was higher than in the control, the degree of mRNA expression was not as high as in Examples 1 and 2.

[0081] Based on these results, it was suggested that skin elasticity improving agents containing EN as an active ingredient have the effect of promoting the synthesis of type I collagen, lysyl oxidase, fibrillin-1, tropoelastin, and emylin-1.

[0082] <Examples 3-1 to 3-6: Evaluation of Type I Collagen Synthesis Promotion 1> EN is used as a skin elasticity improving agent. Normal human dermal fibroblasts (NHDF) are measured in 2.0 × 10⁻⁶ units. 4 Cells were seeded at a cell density of cells / well, and test samples were added, consisting of solutions with EN concentrations of 6.3 μM, 12.5 μM, 25 μM, 50 μM, 100 μM, or 200 μM, respectively. The cells were then cultured at 37°C for 48 hours. After culturing, the NHDF was centrifuged, and the amount of type I collagen in the supernatant was measured by ELISA using a plate reader (Spark 10M, Tecan Japan). The results are shown in the table. This is shown in Figures 2 and 6.

[0083] <Comparative Example 4: Evaluation of Type I Collagen Synthesis Promotion 1> The amount of collagen was measured in the same manner as in Example 3-1, except that the test sample containing a skin elasticity improving agent was not added (control). The results are shown in Table 2 and Figure 6.

[0084] <Comparative Example 5-1~5-5: Evaluation of Type I Collagen Synthesis Promotion 1> VE is used as a skin elasticity improving agent. The amount of collagen was measured in the same manner as in Example 3-1, except that solutions with VE concentrations of 12.5 μM, 25 μM, 50 μM, 100 μM, or 200 μM were used as test samples. The results are shown in Table 2 and Figure 6.

[0085] [Table 2]

[0086] <Examples 4-1 to 4-6: Evaluation of Type I Collagen Synthesis Promotion 2> EN is used as a skin elasticity improving agent. Normal human dermal fibroblasts (NHDF) are measured in 2.0 × 10⁻⁶ units. 4 Cells were seeded at a cell density of cells / well, and test samples were added, consisting of solutions with EN concentrations of 6.3 μM, 12.5 μM, 25 μM, 50 μM, 100 μM, or 200 μM, respectively. The cells were then cultured at 37°C for 48 hours. After culturing, the NHDF was centrifuged, and the amount of type I collagen in the supernatant was measured by ELISA using a plate reader (Spark 10M, Tecan Japan). The results are shown in the table. This is shown in Figures 3 and 7.

[0087] <Comparative Example 6: Evaluation of Type I Collagen Synthesis Promotion 2> The amount of collagen was measured in the same manner as in Example 4-1, except that the test sample containing a skin elasticity improving agent was not added (control). The results are shown in Table 3 and Figure 7.

[0088] <Comparative Example 7-1~7-5: Evaluation of Type I Collagen Synthesis Promotion 2> VE is used as a skin elasticity improving agent. The amount of collagen was measured in the same manner as in Example 4-1, except that solutions with VE concentrations of 12.5 μM, 25 μM, 50 μM, 100 μM, or 200 μM were used as test samples. The results are shown in Table 3 and Figure 7.

[0089] [Table 3]

[0090] Tables 2-3 and Figures 6-7 show that in Examples 3-1 to 3-6 and 4-1 to 4-6, where a skin elasticity improving agent containing EN was applied, the amount of type I collagen in NHDF increased compared to the control (Comparative Examples 4 and 6). Furthermore, it was found that the increase in type I collagen increased as the EN concentration in the test sample increased. Therefore, these examples demonstrate that skin elasticity agents containing EN have a high type I collagen synthesis promoting effect.

[0091] On the other hand, in Comparative Examples 5-1 to 5-5, which used skin elasticity improving agents containing VE, the amount of type I collagen was lower than in the control (Comparative Example 4). Furthermore, the amount of collagen decreased as the VE concentration in the test sample increased. In other words, it was shown that VE inhibits type I collagen synthesis at high concentrations.

[0092] In Comparative Examples 7-1 to 7-5, which used skin elasticity improving agents containing NA, the amount of type I collagen was similar to that of the control (Comparative Example 6). This indicates that NA has little effect in promoting the synthesis of type I collagen.

[0093] <Example 5: Evaluation of Type I Collagen Fiber Formation Promotion> Normal human dermal fibroblasts (NHDF) are measured in 2.0 × 10⁻⁶ units. 4 Cells were seeded at a cell density of cells / well, and after adding the test sample obtained in Example 2, they were cultured at 37°C for 7 days. Subsequently, immunofluorescence staining of type I collagen, which constitutes type I collagen fibers, was performed, and fluorescence observation was carried out at 200x magnification using a fluorescence microscope (BZ-X800, Keyence). The obtained fluorescent stained images are shown in Figure 8. Furthermore, the amount of type I collagen fiber bundles was determined by processing the fluorescent stained images using image processing software and calculating the fluorescence amount as a relative value, with the fluorescence amount in the system without the skin elasticity improving agent (Comparative Example 8) set to 100%. The results are shown in Table 4 and Figure 9.

[0094] <Comparative Example 8: Evaluation of Type I Collagen Fiber Formation Promotion> Except for setting the test sample without the skin elasticity improving agent (control), fluorescence observation of type I collagen fibers and quantification of fluorescence levels were performed in the same manner as in Example 5. The obtained fluorescence stained images are shown in Figure 8, and the determined amount of type I collagen fiber bundles are shown in Table 4 and Figure 9.

[0095] <Comparative Example 9: Evaluation of Type I Collagen Fiber Formation Promotion> Fluorescence observation and quantification of fluorescence levels of type I collagen fibers were performed in the same manner as in Example 5, except that the test sample from Comparative Example 2 was used. The obtained fluorescence stained images are shown in Figure 8, and the determined amount of type I collagen fiber bundles are shown in Table 4 and Figure 9.

[0096] <Comparative Example 10: Evaluation of Type I Collagen Fiber Formation Promotion> Fluorescence observation and quantification of fluorescence levels of type I collagen fibers were performed in the same manner as in Example 5, except that the test sample from Comparative Example 3 was used. The obtained fluorescence stained images are shown in Figure 8, and the determined amount of type I collagen fiber bundles are shown in Table 4 and Figure 9.

[0097] [Table 4]

[0098] Table 4 and Figure 9 show that in Example 5, where a skin elasticity improving agent containing EN as the active ingredient was applied, the amount of type I collagen fibers was significantly higher compared to the control (Comparative Example 8), and the thickness and length of individual fibers, as well as the thickness of fiber bundles, also increased significantly. In other words, it was shown that the skin elasticity improving agent containing EN has a significantly higher effect in promoting type I collagen fiber formation.

[0099] On the other hand, in Comparative Example 9, which used a skin elasticity improving agent containing VE, and Comparative Example 10, which used a skin elasticity improving agent containing NA, the formation of type I collagen fibers was less advanced than in Example 5. These results indicate that both VE and NA have a low effect in promoting type I collagen fiber formation.

[0100] <Example 6: Evaluation of the promotion of elastic fiber formation> Normal human dermal fibroblasts (NHDF) are measured in 2.0 × 10⁻⁶ units. 4 Cells were seeded at a cell density of cells / well, and the test sample obtained in Example 2 was added. The cells were then cultured at 37°C for 7 days. Subsequently, immunofluorescence staining for fibrillin-1, the main component of elastic fibers, was performed, and fluorescence observation was carried out at 200x magnification using a fluorescence microscope (BZ-X800, Keyence). The resulting fluorescent stained images are shown in Figure 10.

[0101] <Comparative Example 11: Evaluation of the promotion of elastic fiber formation> Except for the condition (control) in which no test sample containing a skin elasticity improving agent was added, the actual results were as follows: Fluorescence observation of elastic fibers was performed in the same manner as in Example 6. The obtained fluorescent stained images are shown in Figure 10.

[0102] <Comparative Example 12: Evaluation of the promotion of elastic fiber formation> Fluorescence observation of elastic fibers was performed in the same manner as in Example 6, except that the test sample from Comparative Example 2 was used. The obtained fluorescent stained images are shown in Figure 10.

[0103] <Comparative Example 13: Evaluation of the promotion of elastic fiber formation> Fluorescence observation of elastic fibers was performed in the same manner as in Example 6, except that the test sample from Comparative Example 3 was used. The obtained fluorescent stained images are shown in Figure 10.

[0104] As shown in Figure 10, in Example 6, where a skin elasticity improving agent containing EN was applied, the amount of elastic fibers was greater compared to the control (Comparative Example 11), and the thickness and length of individual fibers, as well as the thickness of fiber bundles, were also increased, confirming the effect of the skin elasticity improving agent containing EN on promoting elastic fiber formation.

[0105] In Comparative Example 13, which used a skin elasticity improving agent containing NA, the formation of elastic fibers was similar to that in Example 6. Furthermore, in Comparative Example 12, which used a skin elasticity improving agent containing VE, the formation of elastic fibers was similar to that of the control (Comparative Example 11).

[0106] The following are examples of formulations for cosmetic compositions and pharmaceutical external compositions for improving skin elasticity, which are topical skin preparations of the present invention.

[0107] <Example prescription 1: Lotion> Skin elasticity improving agent (active ingredient: EN) 2.0% by weight 1,3-Butylene glycol 5.0% by weight Methylparaben 0.3% by weight Glycerin 15.0% by weight Phenoxyethanol 0.5% by weight Carboxyvinyl polymer 9.0% by weight Potassium hydroxide 0.4% by weight Purified water (appropriate amount) Total 100.0% by weight

[0108] <Prescription Example 2: Cream> Skin elasticity improving agent (active ingredient: EN) 2.0% by weight Glycerin 10.0% by weight Ethanol 0.4% by weight Squalane 5.0% by weight Cetanol 3.0% by weight Beeswax 3.0% by weight Arginine 0.3% by weight Fragrance (appropriate amount) Purified water (appropriate amount) Total 100.0% by weight

Claims

1. A type I collagen fiber formation promoter containing either or both tocopherol nicotinate and tocotrienol nicotinate as active ingredients.

2. The type I collagen fiber formation promoter according to claim 1, wherein the promotion of type I collagen fiber formation is due to increased expression of extracellular matrix-related genes and promotion of extracellular matrix protein synthesis.

3. The type I collagen fiber formation promoter according to claim 2, wherein the aforementioned type I collagen fiber formation promotion is further due to the promotion of fiber formation.

4. The type I collagen fiber formation promoter according to claim 2 or 3, wherein the extracellular matrix-related gene is one or more selected from the group consisting of type I collagen gene, lysyl oxidase gene, fibrillin-1 gene, tropoelastin gene, and emylin-1 gene.

5. The type I collagen fiber formation promoter according to claim 3, wherein the extracellular matrix protein is type I collagen and the fiber is a type I collagen fiber.

6. A type I collagen fiber formation promoter according to any one of claims 1 to 5, wherein the total content of tocopherol nicotinate and tocotrienol nicotinate is 85% by weight or more and 100% by weight or less.

7. A topical skin preparation for improving skin elasticity, comprising a type I collagen fiber formation promoter according to any one of claims 1 to 6.

8. A topical skin preparation according to claim 7, which is a cosmetic composition or a topical pharmaceutical composition.

9. A method for improving skin elasticity (excluding medical procedures performed on humans), comprising the step of applying the topical skin preparation described in claim 7 or 8 to the skin surface.

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