Epidermal keratinocyte growth stimulator, skin turnover promoter, skin metabolism promoter, topical skin composition, epidermal keratinocyte growth stimulation method, skin turnover promoting method, and skin metabolism promoting method

Abstract

To provide preparations that can prevent deterioration of skin metabolism function caused by various factors such as aging and ultraviolet disorders, a decrease in the speed of epidermal turnover, and deterioration of the skin environment caused thereby, and thereby can prevent skin aging phenomena such as fine wrinkles and dullness of the skin, and aging odor, scalp odor and the like.SOLUTION: An epidermal keratinocyte growth stimulator, a skin turnover promoter, a skin metabolism promoter, or a topical skin composition containing them, characterized by containing as an active ingredient a lactone compound represented by formula (I), wherein they are used for preventing and / or improving at least one symptom selected from the group consisting of fine wrinkles of skin, darkening, lost texture, degraded firmness, pigmentation, tone-down of skin, stiff skin, rough skin, aging odor, and scalp odor. (In the formula, R is an alkyl group having 2 to 9 carbon atoms).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an epidermal keratinocyte proliferation promoter, a skin turnover promoter, a skin metabolism promoter, an external skin composition, a method for promoting epidermal keratinocyte proliferation, a method for promoting skin turnover, and a method for promoting skin metabolism. [Background technology]

[0002] Skin is a layered tissue that covers our bodies and creates a barrier between us and the outside world. It is composed of four layers, starting with the basal layer at the bottom, followed by the spinous layer, granular layer, and stratum corneum. Most of the cells in each layer are keratinocytes differentiated from the basal layer. Keratinocytes divide and proliferate in the basal layer, differentiate into corneocytes as they pass through the spinous and granular layers, and form the stratum corneum, composed of tightly cross-linked keratin protein fibers. These cells ultimately shed from the stratum corneum as sebum. In normal skin, the outermost stratum corneum acts as a barrier, preventing excessive moisture loss and preventing the intrusion of foreign substances, such as bacteria and harmful substances, from the outside world (see Non-Patent Documents 1 and 2). To maintain this barrier function, the skin undergoes a cycle of epidermal metabolism, from keratinocyte production in the basal layer to sebum shedding (keratinization), which typically repeats every four weeks (skin turnover).

[0003] However, when the proliferation and division ability of epidermal keratinocytes declines due to various factors such as aging and damage caused by excessive ultraviolet rays, the metabolic function of epidermal keratinocytes declines, slowing the rate of epidermal turnover (see Non-Patent Documents 1 and 2). This leads to thinning of the epidermis and thickening of the stratum corneum, which can cause fine wrinkles and rough skin, as well as impaired excretion of melanin, leading to pigmentation and dull skin (see Non-Patent Documents 2 and 3).

[0004] Therefore, if the proliferation of epidermal keratinocytes can be promoted, skin turnover will be promoted, and the skin's metabolic function will be restored, which is thought to improve skin conditions such as fine wrinkles, dullness, and pigmentation. Regarding substances with epidermal keratinocyte proliferation-promoting activity, for example, some herbal medicines have been reported to have epidermal keratinocyte proliferation-promoting activity (see Non-Patent Document 4). Furthermore, an epidermal keratinocyte proliferation promoter containing an extract of the germ found in the seeds of lotus (Nelumbo nucifera Gaertn.) of the Nymphaeaceae family as an active ingredient is known (see Patent Document 1). However, the active ingredient of these substances with epidermal keratinocyte proliferation-promoting activity has not been identified. Other substances known to have epidermal keratinocyte proliferation activity and whose active ingredient has been identified include tranexamic acid or its derivatives (see Patent Document 2) and arbutin (see Patent Document 3).

[0005] On the other hand, lactones have a peach-like or coconut-like scent and are widely and commonly used as fragrance ingredients for perfumes and cosmetics, and as flavor ingredients for food. Other functions of lactones besides fragrances are known, such as suppressing the odor of dampness, scalp odor, and other unpleasant odors (see Patent Documents 4 to 6), and improving body odor (see Patent Document 7). Regarding other pharmacological effects of lactones, γ-decanolactone has been shown to have anticonvulsant properties in a mouse experimental model (see Non-Patent Document 5), but other effects are unknown. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Laid-Open No. 2002-68993 [Patent Document 2] Japanese Patent Application Laid-Open No. 2015-34155 [Patent Document 3] Japanese Patent Application Laid-Open No. 2011-173831 [Patent Document 4] Japanese Patent Application Laid-Open No. 2015-221956 [Patent Document 5] Japanese Patent Application Laid-Open No. 2015-151531 [Patent Document 6] Japanese Patent Application Laid-Open No. 2015-193643 [Patent Document 7] Japanese Patent Application Laid-Open No. 2015-131825 [Non-patent literature]

[0007] [Non-Patent Document 1] Cosmetic Technology Journal, Vol. 23, No. 1, 1989 [Non-patent document 2] Production Research, 59, 124-127, 2007 [Non-patent document 3] J Gerontol., 38(2), 137-42, 1983 [Non-patent document 4] Journal of Japanese and Chinese Medicine, Vol. 15, p. 426-427, 1998 [Non-patent document 5] J Ethnopharmacology, 58, No.3, 175-81, 1997 Summary of the Invention [Problem to be solved by the invention]

[0008] The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a preparation that can prevent / ameliorate the decline in skin metabolic function and the slowdown in epidermal turnover rate caused by various factors such as aging and damage caused by ultraviolet rays, and the resulting deterioration of the skin environment, thereby preventing / ameliorating so-called skin aging phenomena such as fine wrinkles, dullness, loss of skin texture, loss of firmness, pigmentation, skin tone reduction, rough skin, and rough skin, as well as body odor associated with aging and head odor (including scalp odor), which are thought to be caused in part by an imbalance of resident bacteria due to a deterioration of the skin environment. [Means for solving the problem]

[0009] As a result of intensive research to solve the above problems, the present inventors have discovered that lactones, which have been widely used as fragrances, have the function of promoting the proliferation of epidermal keratinocytes, and have thus completed the present invention.

[0010] [1] An agent for promoting proliferation of epidermal keratinocytes, characterized by comprising, as an active ingredient, a lactone compound represented by the following formula (I): [ka] (In the formula, R is an alkyl group having 2 to 9 carbon atoms.) [2] A skin turnover promoter comprising, as an active ingredient, a lactone compound represented by the following formula (I): [ka] (In the formula, R is an alkyl group having 2 to 9 carbon atoms.) [3] A skin metabolism promoter comprising a lactone compound represented by the following formula (I) as an active ingredient: [ka] (In the formula, R is an alkyl group having 2 to 9 carbon atoms.) [4] The enhancer according to any one of [1] to [3], which is used to prevent and / or improve at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of texture, loss of firmness, pigmentation, skin tone loss, rough skin, skin odour due to aging, and scalp odour. [5] The enhancer according to any one of [1] to [4], which is for external use. [6] A composition for external application to the skin containing the promoter according to any one of [1] to [4] for promoting epidermal keratinocyte proliferation, promoting skin turnover, restoring the metabolic function of the skin, or preventing and / or improving at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of skin texture, loss of firmness, pigmentation, skin tone loss, rough skin, skin odour due to aging, and scalp odour. [7] A method for promoting proliferation of epidermal keratinocytes, characterized by using a lactone compound represented by the following formula (I): [ka] (In the formula, R is an alkyl group having 2 to 9 carbon atoms.) [8] A method for promoting skin turnover, characterized by using a lactone compound represented by the following formula (I): [ka] (In the formula, R is an alkyl group having 2 to 9 carbon atoms.) [9] A method for promoting skin metabolism, comprising using a lactone compound represented by the following formula (I): [ka] (In the formula, R is an alkyl group having 2 to 9 carbon atoms.)

[10] The method for promoting skin health described in [7] to [9], which is used to prevent and / or improve at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of texture, loss of firmness, pigmentation, skin tone loss, rough skin, skin odour due to aging, and scalp odour. [Effects of the Invention]

[0011] According to the present invention, it is possible to provide an epidermal keratinocyte proliferation promoter, a skin turnover promoter, and a skin metabolism promoter that can prevent / ameliorate the decline in skin metabolic function and the slowdown in epidermal turnover rate caused by various factors such as aging and damage caused by ultraviolet rays, and the resulting deterioration of the skin environment, thereby preventing skin aging phenomena such as fine wrinkles, dullness, and pigmentation, as well as body odor and head odor (including scalp odor), which are thought to be caused in part by an imbalance of resident bacteria due to a deterioration of the skin environment. These accelerators of the present invention have the effect of promoting epidermal keratinocyte proliferation, the effect of promoting skin turnover, the effect of restoring the metabolic function of the skin, or the effect of preventing and / or improving at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of skin texture, loss of firmness, pigmentation, skin tone reduction, rough skin, skin odour due to aging, and head odour (including scalp odour), and are therefore suitable for use in external skin compositions such as cosmetics and quasi-drugs that are expected to have such effects. [Brief explanation of the drawings]

[0012] [Figure 1] FIG. 1 shows the proliferation-promoting effect of lactones on human epidermal keratinocytes. DETAILED DESCRIPTION OF THE INVENTION

[0013] The present invention will be described in detail below. The terms used in this specification are to be interpreted in the sense commonly used in the art unless otherwise specified.

[0014] [Epidermal keratinocyte proliferation promoter] The epidermal keratinocyte proliferation promoter of the present invention is characterized by containing a lactone compound represented by the following formula (I) as an active ingredient. By containing the lactone compound, the epidermal keratinocyte proliferation promoter of the present invention has the effect of promoting the proliferation of epidermal keratinocytes in the skin, thereby promoting skin turnover and restoring the skin's metabolic function. It is believed that when skin turnover slows due to aging or other causes, melanin excretion becomes poor, making pigmentation and dullness more likely to occur. Furthermore, a decline in skin metabolism is thought to worsen the skin environment, disrupting the balance of resident bacteria on the skin (including the scalp), and increasing odor-causing bacteria, leading to the development of body odor, head odor, and other conditions. Therefore, when skin turnover is promoted by the epidermal keratinocyte proliferation promoter of the present invention, pigmentation and dullness can be suppressed and melanin excretion function can be improved, and skin tone can be improved, improving skin clarity and luster. It can also prevent / ameliorate skin problems such as fine wrinkles, loss of skin texture, loss of firmness, rough skin, and skin irritation, as well as body odor associated with aging and head odor. That is, the epidermal keratinocyte proliferation promoter of the present invention is suitable for use in preventing and / or ameliorating at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of skin texture, loss of firmness, pigmentation, skin tone reduction, rough skin, skin irritation, body odor associated with aging, and head odor. In this specification, head odor is a concept that also includes scalp odor. [ka]

[0015] In the formula, R is an alkyl group having 2 to 9 carbon atoms. The number of carbon atoms in R is preferably 3 to 9, more preferably 4 to 9, even more preferably 5 to 8, and particularly preferably 6 or 7. The hydrogen atoms contained in the alkyl group may be substituted.

[0016] Specific examples of lactone compounds represented by the above formula (I) include γ-hexalactone, γ-heptalactone, γ-octalactone, γ-nonalactone, γ-decalactone, γ-undecalactone, γ-dodecalactone, and γ-tridecalactone. Of these, γ-nonalactone, γ-decalactone, γ-undecalactone, and γ-dodecalactone are preferred, with γ-decalactone and γ-undecalactone being more preferred. These lactone compounds are components that have the scent of fruits such as peach, apricot, and coconut. The lactone compounds may be used alone or in combination of two or more.

[0017] The content of the lactone compound represented by formula (I) contained in the epidermal keratinocyte proliferation promoter of the present invention is 0.0000001 to 10% by weight. From the viewpoint of the epidermal keratinocyte proliferation promoting effect, it is preferably 0.0000005 to 5% by weight, more preferably 0.000001 to 3% by weight, even more preferably 0.000005 to 2% by weight, and particularly preferably 0.00001 to 1% by weight. Furthermore, when used diluted, such as in bath additives, the content of the lactone compound can be adjusted taking into account the content after dilution. For example, in the case of bath additives, it is preferably 0.001 to 10% by weight, more preferably 0.001 to 5% by weight. Furthermore, when two or more lactone compounds are used in combination, the total amount thereof falls within the above-mentioned numerical range.

[0018] The pH of the epidermal keratinocyte proliferation promoter of the present invention is usually pH 3.0 to 8.0, and preferably pH 3.5 to 7.5. This pH can be adjusted, for example, by using a pH adjuster as described below.

[0019] The epidermal keratinocyte proliferation promoter of the present invention may consist solely of the lactone compound, or may be a formulation prepared by blending the lactone compound with ingredients necessary for formulation. When formulated, it can be prepared in any dosage form, such as powder, granules, tablets, or liquid, using a pharmaceutically acceptable base material, carrier, or any other additive, according to a conventional method. The epidermal keratinocyte proliferation promoter of the present invention can be used itself as an external preparation, ointment, patch, etc., or, as described below, the epidermal keratinocyte proliferation promoter can be blended with other compositions, such as an external composition for skin, for use.

[0020] <Formulation of the epidermal keratinocyte proliferation promoter of the present invention> The epidermal keratinocyte proliferation promoter of the present invention can be prepared into various formulations by mixing it in a conventional manner with a base or carrier commonly used in cosmetics, pharmaceuticals, and quasi-drugs, and, if necessary, with the additives described below, and emulsifying or solubilizing it as necessary.

[0021] (substrate, carrier) Examples of the base or carrier include hydrocarbons such as liquid paraffin, squalane, petrolatum, gelling hydrocarbons (such as Plastibase), ozokerite, α-olefin oligomers, and light liquid paraffin; silicone oils such as methyl polysiloxane, highly polymerized methyl polysiloxane, cyclic silicone, alkyl-modified silicone, amino-modified silicone, polyether-modified silicone, polyglycerin-modified silicone, silicone / alkyl chain co-modified polyether-modified silicone, silicone / alkyl chain co-modified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicone, phenyl-modified silicone, and silicone resin; oils and fats such as coconut oil, olive oil, rice bran oil, and shea butter; waxes such as jojoba oil, bee wax, candelilla wax, and lanolin; higher alcohols such as cetyl alcohol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, octyldodecanol, isostearyl alcohol, phytosterol, and cholesterol; and cellulose derivatives such as ethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methylcellulose. Conductors; polyvinylpyrrolidone; carrageenan; polyvinyl butyrate; polyethylene glycol; dioxane; butylene glycol adipate polyester; esters such as diisopropyl adipate, isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, and pentaerythritol tetra-2-ethylhexanoate; polysaccharides such as dextrin and maltodextrin; vinyl polymers such as carboxyvinyl polymers and alkyl-modified carboxyvinyl polymers; lower alcohols such as ethanol and isopropanol; glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl 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;Water, etc.

[0022] In the epidermal keratinocyte proliferation promoter of the present invention, these bases or carriers may be used alone or in combination of two or more, and the amounts used may be appropriately selected from ranges known to those skilled in the art.

[0023] (additives) The epidermal keratinocyte proliferation promoter of the present invention may contain known additives added to cosmetics, pharmaceuticals, and quasi-drugs, such as surfactants, stabilizers, antioxidants, colorants, pearlescent agents, dispersants, chelating agents, pH adjusters, preservatives, thickeners, and irritation reducers, within the scope of not impairing the effects of the present invention. These additives may be used alone or in combination of two or more.

[0024] The surfactant may be any of a nonionic surfactant, a cationic surfactant, an anionic surfactant, an amphoteric surfactant, and the like, and examples thereof include sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, and diglycerol sorbitan tetra-2-ethylhexylate; 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; polyoxyethylene monolaurate; Examples of surfactants include polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan (polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate 80), and polyoxyethylene (20) sorbitan isostearate; polyoxyethylene monoglyceryl cocoate; glycerin alkyl ethers; alkyl glucosides; polyoxyalkylene alkyl ethers such as polyoxyethylene cetyl ether; amines such as stearylamine and oleylamine; and silicone surfactants such as polyoxyethylene-methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone.

[0025] Examples of the stabilizer include sodium polyacrylate, dibutylhydroxytoluene, and butylhydroxyanisole.

[0026] Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, erythorbic acid, and L-cysteine ​​hydrochloride.

[0027] Examples of the colorant include inorganic pigments and natural dyes.

[0028] Examples of the pearly luster imparting agent include ethylene glycol distearate, ethylene glycol monostearate, and triethylene glycol distearate.

[0029] Examples of the dispersant include sodium pyrophosphate, sodium hexametaphosphate, polyvinyl alcohol, polyvinylpyrrolidone, methyl vinyl ether / maleic anhydride crosslinked copolymer, and organic acids.

[0030] Examples of the chelating agent include EDTA disodium salt, EDTA calcium disodium salt, and the like.

[0031] 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, sodium hydroxide, etc.), and organic bases (triethanolamine, diisopropanolamine, triisopropanolamine, etc.).

[0032] Examples of the preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, benzyl parahydroxybenzoate, methyl parahydroxybenzoate, and phenoxyethanol.

[0033] Examples of the thickener include vinyl thickeners such as polyvinyl alcohol, polyvinylpyrrolidone, and carboxyvinyl polymers; cellulose thickeners such as methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose, and carboxyethyl cellulose; guar gum, pectin, pullulan, gelatin, locust bean gum, carrageenan, agar, xanthan gum, acrylates / alkyl methacrylate copolymers, polyethylene glycol, bentonite, alginic acid, propylene glycol alginate, macrogol, sodium chondroitin sulfate, hyaluronic acid, sodium hyaluronate, (hydroxyethyl acrylate / sodium acryloyldimethyltaurate) copolymer, and (ammonium acryloyldimethyltaurate / vinylpyrrolidone) copolymer.

[0034] Examples of the irritation reducer include licorice extract, sodium alginate, gum arabic, polyvinylpyrrolidone, and the like.

[0035] (Form of formulation) The formulation of the epidermal keratinocyte proliferation promoter of the present invention is not particularly limited, and examples thereof include skin care products (lotions, emulsions, serums, creams, etc.), makeup cosmetics, base cosmetics, cleansing agents such as body soap and facial cleansers, shampoos, treatments, dry shampoos, scalp care products, hair mists, hair care products such as hair growth agents and hair growth promoters, cleansing agents, wipe-off lotions, deodorants, antiperspirants, bath additives, ointments, liquids, suspensions, emulsions (lotions and creams), gels, liniments, lotions, poultices, mists, aerosols, powders, granules, tablets (including effervescent tablets), and solid soaps. Liquid to semisolid formulations are preferred, and liquids, lotions, ointments, gels, and emulsions are particularly useful. These formulations can be prepared according to conventional methods, such as those described in the General Provisions of Preparations in the 17th Edition of the Japanese Pharmacopoeia. The epidermal keratinocyte proliferation promoter of the present invention may also be impregnated into a nonwoven fabric.The epidermal keratinocyte proliferation promoter of the present invention is particularly suitable for use as an external preparation for the purpose of anti-aging.

[0036] [Skin turnover promoter] The skin turnover accelerator of the present invention is characterized by containing a lactone compound represented by formula (I) as an active ingredient. By containing the lactone compound, the skin turnover accelerator of the present invention has the effect of promoting the proliferation of epidermal keratinocytes in the skin, thereby promoting skin turnover and facilitating the skin's metabolic function. It is believed that when skin turnover slows due to aging or other causes, melanin excretion becomes poor, making pigmentation and dullness more likely to occur. Furthermore, a decline in skin metabolism is thought to worsen the skin environment, disrupt the balance of resident bacteria on the skin (including the scalp), and increase odor-causing bacteria, leading to the development of body odor, head odor, and other conditions. Therefore, when skin turnover is promoted by the skin turnover accelerator of the present invention, pigmentation and dullness can be suppressed and melanin excretion function can be improved, and skin tone can be improved, improving skin clarity and luster. It can also prevent / ameliorate skin problems such as fine wrinkles, loss of skin texture, loss of firmness, rough skin, and skin irritation, as well as body odor and scalp odor. That is, the skin turnover promoter of the present invention is suitably used for preventing and / or ameliorating at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of skin texture, loss of firmness, pigmentation, skin tone reduction, rough skin, skin irritation, skin irritation, and scalp odor. The specific description of the skin turnover promoter of the present invention can be applied as is by replacing the epidermal keratinocyte proliferation promoter with the skin turnover promoter in the description of the epidermal keratinocyte proliferation promoter of the present invention described above.

[0037] [Skin metabolism promoter] The skin metabolism enhancer of the present invention is characterized by containing a lactone compound represented by formula (I) as an active ingredient. By containing the lactone compound, the skin metabolism enhancer of the present invention has the effect of promoting the proliferation of epidermal keratinocytes in the skin, thereby promoting skin turnover and facilitating the skin's metabolic function. It is believed that when skin turnover slows and the skin's metabolic function declines due to aging or other causes, melanin excretion becomes impaired, making the skin more susceptible to pigmentation and dullness. Therefore, when the skin metabolism enhancer of the present invention promotes the skin's metabolic function, it can inhibit pigmentation and dullness and improve the melanin excretion function, thereby promising a skin tone-up effect, improved skin clarity, and improved skin luster. Furthermore, it is believed that a decline in skin metabolism can worsen the skin environment, disrupt the balance of resident bacteria on the skin (including the scalp), and increase odor-causing bacteria, leading to the development of body odor associated with aging, head odor, and other conditions. It can also prevent / ameliorate skin problems such as fine wrinkles, loss of skin texture, loss of firmness, rough skin, and skin irritation, as well as body odor associated with aging and head odor. That is, the skin metabolism promoter of the present invention is suitably used for preventing and / or ameliorating at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of skin texture, loss of firmness, pigmentation, skin tone reduction, rough skin, skin irritation, skin irritation, body odor associated with aging, and head odor. The specific description of the skin metabolism promoter of the present invention can be directly applied by replacing the epidermal keratinocyte proliferation promoter with the skin metabolism promoter in the description of the epidermal keratinocyte proliferation promoter of the present invention described above.

[0038] [Skin external composition] The epidermal keratinocyte proliferation promoter, skin turnover promoter, and skin metabolism promoter of the present invention can also be incorporated into other compositions and used as a topical skin composition. The present invention also includes a topical skin composition containing the epidermal keratinocyte proliferation promoter, skin turnover promoter, or skin metabolism promoter of the present invention. By containing the epidermal keratinocyte proliferation promoter, skin turnover promoter, or skin metabolism promoter of the present invention, the topical skin composition of the present invention exhibits the effects of promoting epidermal keratinocyte proliferation, promoting skin turnover, and promoting skin metabolism, and is therefore suitable for use in preventing and / or improving at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of skin texture, loss of firmness, pigmentation, skin tone loss, rough skin, rough skin, body odor, and scalp odor.

[0039] In addition to the lactone compound represented by formula (I) above, which is an essential ingredient of the epidermal keratinocyte proliferation promoter, skin turnover promoter, and skin metabolism promoter of the present invention, the topical skin composition of the present invention may contain the following optional ingredients within a range that does not impair the effects of the present invention.

[0040] Examples of optional ingredients that the topical skin composition of the present invention may contain in addition to the above-mentioned essential ingredients include anti-inflammatory agents, cooling agents, disinfectants, vitamins, organic acids, moisturizing ingredients, polyhydric alcohols, scrubbing agents, UV-absorbing ingredients, UV-scattering ingredients, astringent ingredients, peptides or derivatives thereof, amino acids or derivatives thereof, cleansing ingredients, keratin softening ingredients, cell-activating ingredients (excluding the lactones of the present invention), anti-aging ingredients (excluding the lactones of the present invention), blood circulation-promoting ingredients, whitening ingredients, powders, etc. In the topical skin composition of the present invention, these ingredients may be used alone or in combination of two or more.

[0041] Examples of anti-inflammatory agents include allantoin and its derivatives, glycyrrhetinic acid and its derivatives, glycyrrhizinic acid and its derivatives, salicylic acid derivatives, aminocaproic acid, azulene and its derivatives, zinc oxide, tocopherol acetate, hydrocortisone, prednisolone, and salts thereof. Among these, allantoin, allantoin chlorohydroxyaluminum, allantoin dihydroxyaluminum, glycyrrhetinic acid, glycyrrhizinic acid, stearyl glycyrrhetinate, glycol salicylate, methyl salicylate, epsilon aminocaproic acid, azulene, guaiazulene, and salts thereof are preferred. Here, "derivatives" refers to esters, ethers, alkylated products, glycosides, etc. of the compounds described. Here, "salts" refers to, for example, salts of mineral acids such as sulfuric acid, hydrochloric acid, or phosphoric acid, salts of organic acids such as maleic acid or methanesulfonic acid, alkali metal salts such as sodium or potassium, alkaline earth metal salts, ammonium salts, etc.

[0042] Examples of the refreshing agent include terpenes such as menthol, camphor, borneol, geraniol, cineole, anethole, limonene, and eugenol (which may be in the d-, l-, or dl-form); and essential oils such as eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spearmint oil, fennel oil, peppermint oil, cinnamon oil, rose oil, and turpentine.

[0043] Examples of the disinfectants include isopropylmethylphenol, chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, ethanol, benzethonium chloride, cresol, gluconic acid and its derivatives, povidone-iodine, potassium iodide, iodine, triclocarban, triclosan, photosensitizer No. 101, photosensitizer No. 201, paraben, phenoxyethanol, 1,2-pentanediol, alkyldiaminoglycine hydrochloride, piroctoolamine, and miconazole.

[0044] The vitamins may be either water-soluble or oil-soluble vitamins, and examples thereof include vitamin B6s such as pyridoxine, pyridoxal, pyridoxamine, 5'-pyridoxal phosphate, and salts thereof (e.g., pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, pyridoxamine hydrochloride); pantothenic acids such as pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-pantethine, D-pantethine, coenzyme A, pantothenyl ethyl ether, and salts thereof; nicotinic acid, nicotine nicotinic acids such as dl-α-tocopherol nicotinate, benzyl nicotinate, methyl nicotinate, β-butoxyethyl nicotinate, 1-(4-methylphenyl)ethyl nicotinate, nicotinamide, and salts thereof; γ-oryzanol, thiamine, dibenzoylthiamine, thiamine cetyl, thiamine monophosphate, thiamine diphosphate, thiamine triphosphate, and salts thereof (e.g., dibenzoylthiamine hydrochloride, thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine Vitamin B1 compounds such as nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine diphosphate hydrochloride, and thiamine triphosphate monophosphate; Vitamin B2 compounds such as riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5'-phosphate sodium, riboflavin tetranicotinate, and their salts; Vitamin B1 compounds such as biotin, biocytin, and their salts. Vitamins such as folic acid, pteroylglutamic acid, and their salts; vitamin B12 derivatives such as cyanocobalamin, hydroxocobalamin, deoxyadenosylcobalamin, and their salts; water-soluble vitamin C derivatives such as ascorbic acid, dehydroascorbic acid, ascorbic acid phosphate, ascorbic acid-2-glucoside, 3-O-ethyl ascorbic acid, and their salts (e.g., sodium ascorbate, sodium ascorbyl phosphate, magnesium ascorbyl phosphate);Examples of vitamin E compounds include dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, and dl-α-tocopherol calcium succinate; oil-soluble vitamin C compounds such as ascorbigen-A, ascorbyl stearate, ascorbyl palmitate, L-ascorbyl dipalmitate, and ascorbyl tetra-2-hexyldecanoate; vitamin D compounds such as ergocalciferol and cholecalciferol; vitamin K compounds such as phylloquinone and farnoquinone; and vitamin-like factors such as ferulic acid.

[0045] Examples of the organic acids include gluconic acid, aspartic acid, aminoethylsulfonic acid, citric acid, glutamic acid, succinic acid, oxalic acid, fumaric acid, propionic acid, malic acid, salicylic acid, glycolic acid, phytic acid, tartaric acid, acetic acid, lactic acid, and salts thereof. Examples of the salts include salts of mineral acids such as sulfuric acid, hydrochloric acid, and phosphoric acid, salts of organic acids such as maleic acid and methanesulfonic acid, salts of alkali metals such as sodium and potassium, alkaline earth metal salts, and ammonium salts.

[0046] Examples of the moisturizing components include diglycerin trehalose; polymeric compounds such as sodium hyaluronate, heparinoids, sodium chondroitin sulfate, collagen, elastin, keratin, chitin, and chitosan; amino acids such as glycine, aspartic acid, and arginine; natural moisturizing factors such as sodium lactate, urea, and sodium pyrrolidonecarboxylate; lipids such as ceramide, cholesterol, and phospholipids; and plant extracts such as chamomile extract, witch hazel extract, tea extract, and perilla extract.

[0047] The polyhydric alcohol preferably has 2 to 10 carbon atoms, and examples thereof include glycerin, diglycerin, triglycerin, propylene glycol, dipropylene glycol, 1,3-butanediol, ethylene glycol, diethylene glycol, isoprene glycol, 1,3-butylene glycol, sorbitol, xylitol, erythritol, mannitol, pentanediol, hexanediol, octanediol, decanediol, and neopentyl glycol.

[0048] Examples of the scrubbing agent include apricot kernel powder, almond shell powder, apricot kernel powder, sodium chloride granules, olive kernel powder, seawater dried granules, candelilla wax, walnut shell powder, cherry kernel powder, coral powder, charcoal powder, hazelnut shell powder, polyethylene powder, and silicic anhydride.

[0049] Examples of the ultraviolet absorbing component include octyl triazone, dimethoxybenzylidene dioxoimidazolidine octyl propionate, 2-ethylhexyl paramethoxycinnamate, and phenylbenzimidazole sulfonic acid.

[0050] Examples of the ultraviolet scattering component include inorganic compounds such as hydrous silicic acid, zinc silicate, cerium silicate, titanium silicate, zirconium oxide, cerium oxide, titanium oxide, iron oxide, and silicic anhydride; these inorganic compounds coated with inorganic powder such as hydrous silicic acid, aluminum hydroxide, mica, and talc; compounds composited with resin powder such as polyamide, polyethylene, polyester, polystyrene, and nylon; and compounds further treated with silicone oil, fatty acid aluminum salt, or the like.

[0051] Examples of the astringent ingredient include zinc sulfate, aluminum chloride, zinc sulfophenol, and tannic acid.

[0052] Examples of the above peptides or derivatives thereof include keratin hydrolyzed peptides, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin hydrolyzed peptides, collagen hydrolyzed peptides, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin hydrolyzed peptides, conchiolin hydrolyzed peptides, hydrolyzed conchiolin, silk proteolytic peptides, hydrolyzed silk, sodium lauroyl hydrolyzed silk, soybean proteolytic peptides, hydrolyzed soybean protein, wheat protein, wheat proteolytic peptides, hydrolyzed wheat protein, casein hydrolyzed peptides, and acylated peptides (palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide, etc.).

[0053] Examples of the amino acids or derivatives thereof 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.

[0054] Examples of the cleansing component include soaps selected from alkali metal salts such as potassium laurate, potassium myristate, potassium palmitate, and potassium stearate, alkanolamide salts, and amino acid salts; amino acid surfactants such as sodium cocoyl glutamate and sodium cocoyl methyl taurate; ether sulfate ester salts such as sodium laureth sulfate; ether carboxylate salts such as sodium lauryl ether acetate; sulfosuccinate ester salts such as sodium alkyl sulfosuccinate; fatty acid alkanolamides such as coconut oil fatty acid monoethanolamide and coconut oil fatty acid diethanolamide; monoalkyl phosphate ester salts such as sodium lauryl phosphate and sodium polyoxyethylene lauryl ether phosphate; betaine-type amphoteric surfactants such as coconut oil fatty acid amidopropyl dimethylaminoacetic acid betaine, lauryl dimethylaminoacetic acid betaine, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, lauryl hydroxysulfobetaine, and sodium lauroylamidoethyl hydroxyethyl carboxymethyl betaine hydroxypropyl phosphate; and amino acid amphoteric surfactants such as sodium lauryl aminopropionate.

[0055] Examples of the keratin softening ingredients include lactic acid, salicylic acid, gluconic acid, citric acid, malic acid, fruit acid, phytic acid, urea, sulfur, and the like.

[0056] Examples of the cell activation components include amino acids such as γ-aminobutyric acid; vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acids; α-hydroxy acids such as glycolic acid and lactic acid; tannins, flavonoids, saponins, and photosensitizer No. 301.

[0057] Examples of the anti-aging ingredients include pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, and N-methyl-L-serine.

[0058] Examples of the blood circulation-promoting component include components derived from plants (e.g., ginseng, angelica tree, arnica, ginkgo, fennel, emmeisou, Dutch oak, chamomile, Roman chamomile, carrot, gentian, burdock, rice, hawthorn, shiitake mushroom, ginger, European hawthorn, European juniper, cnidium rhizome, Swertia japonica, thyme, clove, tangerine peel, chili pepper, angelica acutiloba, peach kernel, spruce, carrot, garlic, butcher's broom, grape, peony, horse chestnut, melissa, yuzu, coix seed, ryokucha, rosemary, rose hip, tangerine peel, angelica acutiloba, spruce, peach, apricot, walnut, corn, etc.); acetylcholine, ichthammol, cantharides tincture, gamma-oryzanol, cepharanthine, tolazoline, tocopherol nicotinate, glucosyl hesperidin, etc.).

[0059] Examples of the whitening ingredients include tocopherol and tranexamic acid.

[0060] Examples of the powder component include starch octenyl succinate Al (starch aluminum octenyl succinate), talc, corn starch, magnesium hydroxide, anhydrous silicic acid, light anhydrous silicic acid, mica, hydroxyapatite, zinc oxide, titanium oxide, nylon powder, and charcoal.

[0061] (pH) The pH of the composition for external use on skin of the present invention is usually pH 3.0 to 8.0, and preferably pH 3.5 to 7.5. This pH can be adjusted, for example, by using the pH adjuster described above.

[0062] <Method of manufacturing a composition for topical use on skin> The method for producing the topical composition of the present invention is not particularly limited, and the composition can be produced by a conventional method by appropriately selecting and blending various ingredients (the above-mentioned optional ingredients, base or carrier, additives, etc.) necessary for producing an epidermal keratinocyte proliferation promoter containing the lactone compound represented by the above formula (I), which is an essential ingredient, a skin turnover promoter or skin metabolism promoter, and a topical skin composition. For details about the above-mentioned base or carrier and additives, see the explanation in the section on skin keratinocyte proliferation promoter.

[0063] <Uses of topical skin compositions> The topical skin composition of the present invention contains the epidermal keratinocyte proliferation promoter, skin turnover promoter, or skin metabolism promoter of the present invention, and therefore exhibits the effects of promoting epidermal keratinocyte proliferation, promoting skin turnover, and promoting skin metabolism, and is therefore suitable for use in preventing and / or improving at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of skin texture, loss of firmness, pigmentation, skin tone reduction, rough skin, rough skin, body odor, and scalp odor. The topical skin composition of the present invention used for such purposes can be used, for example, as skin care products (lotion, emulsion, serum, cream, etc.), makeup cosmetics, base cosmetics, cleansing agents such as body soap and facial cleanser, shampoo, treatment, dry shampoo, scalp care agent, hair mist, hair care agents such as hair growth agents and hair regrowth agents, cleansing agents, deodorants, antiperspirants, ointments, liquids, suspensions, emulsifiers (emulsions and creams), gels, liniments, lotions, poultices, mists, aerosols, powders, granules, solid soaps, etc. It is particularly suitable for use as a topical skin composition for anti-aging purposes.

[0064] [Method for promoting epidermal keratinocyte proliferation, method for promoting skin turnover, method for promoting skin metabolism] The present invention also includes a method for promoting epidermal keratinocyte proliferation, a method for promoting skin turnover, and a method for promoting skin metabolism, each of which uses a lactone compound represented by formula (I). The lactone compound promotes the proliferation of epidermal keratinocytes, thereby promoting skin turnover and restoring skin metabolic function. It is believed that slowing skin turnover due to aging or other causes leads to poor melanin excretion, making skin more susceptible to pigmentation and dullness. Furthermore, a decline in skin metabolism is thought to worsen the skin environment, disrupting the balance of resident bacteria on the skin (including the scalp), leading to an increase in odor-causing bacteria and the development of body odor and head odor. Therefore, promoting skin turnover using the method of the present invention can suppress pigmentation and dullness and improve melanin excretion, potentially resulting in a brighter skin tone, improved skin clarity, and improved skin luster. They can also prevent / ameliorate skin problems such as fine wrinkles, loss of skin texture, loss of firmness, rough skin, and skin irritation, as well as body odor due to aging and scalp odor. That is, the method for promoting epidermal keratinocyte proliferation, the method for promoting skin turnover, and the method for promoting skin metabolism of the present invention are suitably used for preventing and / or ameliorating at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of skin texture, loss of firmness, pigmentation, skin tone reduction, rough skin, skin irritation, body odor due to aging, and scalp odor.

[0065] The method for promoting epidermal keratinocyte proliferation of the present invention can be specifically realized by using the epidermal keratinocyte proliferation promoter of the present invention described above and a topical skin composition containing the same.Furthermore, the method for promoting skin turnover of the present invention can be specifically realized by using the skin turnover promoter of the present invention described above and a topical skin composition containing the same.Furthermore, the method for promoting skin metabolism of the present invention can be specifically realized by using the skin metabolism promoter of the present invention described above and a topical skin composition containing the same. [Example]

[0066] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0067] [Human epidermal keratinocyte proliferation test] Normal human epidermal keratinocytes (NHEK, Kurabo) were induced to sleep and then seeded at the recommended density of 75 cm 2 The cells were seeded into flasks (FALCON) and cultured for 3 days at 37°C under 5% CO2. After harvesting, cells were collected using 0.025% Trypsin-EDTA (Kurabo) and seeded at the desired cell density onto various plates. NHEK cells were seeded into 96-well black plates (Corning) at 5,000 cells / 200 μL / well. After 24 hours of culture, the medium was removed by aspiration, and various lactones diluted to 0.000001% in the medium were added at 200 μL / well. The cells were cultured for an additional 3 days. After the culture, the medium was removed, and Hoechst 33342 (DOJINDO) diluted 1 / 1,000 was added. After incubation for 5 minutes in the dark, the stained nuclei were counted using ImageXpress (Molecular Devices) to determine the cell count. The results are shown in Figure 1.

[0068] As shown in Figure 1, the addition of γ-decalactone and γ-undecalactone to the medium promoted the proliferation of human epidermal keratinocytes. Although data are not shown, it was confirmed that the proliferation-promoting effect of various lactones was also observed even at concentrations of 0.0000001% and 0.00000001%.

[0069] Formulation examples of the topical composition of the present invention are shown below. The numerical values ​​(%) of each lactone listed in Table 1 indicate the final concentration (wt %) in the entire composition when the respective combinations are used in each formulation example.

[0070] <Formulation example 1: Body soap> Any of the lactone compound combinations listed in Table 1 Lauric acid 5% by weight Palmitic acid 5% by weight Stearic acid 5% by weight Potassium hydroxide (appropriate amount) Glycerin 5% by weight Dibutylhydroxytoluene 0.01% by weight Disodium edetate 0.05% by weight Phenoxyethanol 0.3% by weight Benzalkonium chloride 0.1% by weight Sodium laureth sulfate 5% by weight Coconut oil fatty acid amidopropyl betaine 5% by weight Polyquaternium-10 0.5% by weight Polyquaternium-7 0.2% by weight Kaolin 0.5% by weight Charcoal 0.05% by weight Magnesium ascorbyl phosphate 0.5% by weight Hydroxyethyl cellulose 0.3% by weight water remainder Total 100% by weight

[0071] [Table 1]

[0072] <Formulation example 2: Foam-dispensing body wash> Any of the lactone compound combinations listed in Table 1 PEG-80 sorbitan laurate 5% by weight Disodium cocoyl glutamate 4% by weight Sodium cocoyl glycinate 2% by weight Sorbitol 5% by weight Cocoyl methyl taurate sodium taurate 2% by weight Citric acid (appropriate amount) Disodium edetate 0.05% by weight Cocamide DEA 1% by weight Sodium cocoamphoacetate 3% by weight Polyquaternium-7 0.05% by weight Dipotassium glycyrrhizinate 0.3% by weight water remainder Total 100% by weight

[0073] <Formulation example 3: Facial cleanser> Any of the lactone compound combinations listed in Table 1 Lauric acid 5% by weight Myristic acid 10% by weight Palmitic acid 7% by weight Stearic acid 7% by weight Potassium hydroxide (appropriate amount) Butylene glycol 5% by weight Glycerin 5% by weight Tocopherol 0.05% by weight Disodium edetate 0.05% by weight Phenoxyethanol 0.3% by weight Salicylic acid 0.2% by weight Coconut oil fatty acid amidopropyl betaine 5% by weight Polyquaternium-10 0.3% by weight Polyquaternium-7 0.1% by weight l-Menthol 0.3% by weight Fragrance 0.2% by weight water remainder Total 100% by weight

[0074] <Formulation example 4: Shampoo> Any of the lactone compound combinations listed in Table 1 Sodium laureth sulfate 30% by weight Triethanolamine cocoyl glutamate 5% by weight Sodium lauroylmethylalanine 5% by weight Lauramidopropyl hydroxysultaine 5% by weight Citric acid (appropriate amount) Dimethicone 0.3% by weight Methylparaben 0.2% by weight Disodium edetate 0.1% by weight Polyquaternium-10 0.5% by weight Polyquaternium-39 0.1% by weight Polyquaternium-7 0.1% by weight Fragrance 0.8% by weight water remainder Total 100% by weight

[0075] <Formulation example 5: Shampoo> Any of the lactone compound combinations listed in Table 1 Sodium olefin (C14-16) sulfonate 15% by weight POE lauryl ether acetate sodium 5% by weight Coconut oil fatty acid diethanolamide 5% by weight Coconut oil fatty acid TEA liquid 5% by weight Coconut oil fatty acid amidopropyl betaine solution 5% by weight Citric acid (appropriate amount) Disodium edetate 0.1% by weight Benzalkonium chloride 1% by weight Polyquaternium-10 0.6% by weight Polyquaternium-7 0.1% by weight Fragrance 0.5% by weight water remainder Total 100% by weight

[0076] <Formulation example 6: Hair conditioner> Any of the lactone compound combinations listed in Table 1 Glycerin 5% by weight Hyaluronic acid 0.1% by weight Dipotassium glycyrrhizinate 0.1% by weight Squalane 0.1% by weight Stearyltrimethylammonium chloride 4% by weight Polyquaternium-10 0.5% by weight Cetyl alcohol 2% by weight POE-monostearyl glyceryl ether 1% by weight Dibutylhydroxytoluene 0.01% by weight Phenoxyethanol 0.3% by weight EDTA-2Na 0.05% by weight l-Menthol 0.2% by weight Fragrance 0.3% by weight water remainder Total 100% by weight

[0077] <Formulation example 7: Hair treatment> Any of the lactone compound combinations listed in Table 1 Propylene glycol 5% by weight Acetylated hyaluronic acid 0.01% by weight Allantoin 0.3% by weight Tetra-2-ethylhexanoic acid pentastrietate 1% by weight Cetyltrimethylammonium bromide 2.5% by weight Polyquaternium-7 0.1% by weight Cetostearyl alcohol 2% by weight Stearyl alcohol 2% by weight POE-hydrogenated castor oil 1% by weight Dibutylhydroxytoluene 0.01% by weight Methyl parahydroxybenzoate 0.3% by weight EDTA-2Na 0.05% by weight Fragrance 0.5% by weight water remainder Total 100% by weight

[0078] <Formulation example 8: Hair essence> Any of the lactone compound combinations listed in Table 1 Butylene glycol 5% by weight Hydrolyzed hyaluronic acid 0.1% by weight Epsilon aminocaproic acid 0.05% by weight Alkyltrimethylammonium chloride 0.7% by weight O-[2-hydroxy-3-(trimethylammonio) chloride Propyl]guar gum 0.5% by weight Diethylene glycol monoethyl ether 2% by weight POE-sorbitan monoisostearate 0.8% by weight Ethanol 20% by weight Phenoxyethanol 0.3% by weight Fragrance 0.1% by weight water remainder Total 100% by weight

[0079] <Formulation example 9: Hair mist> Any of the lactone compound combinations listed in Table 1 Hydrolyzed collagen 1% by weight Butylene glycol 5% by weight Hydrolyzed hyaluronic acid 0.1% by weight Dipotassium glycyrrhizinate 0.05% by weight Polyquaternium-51 0.5% by weight Liquid paraffin 0.5% by weight Monoisostearyl glyceryl ether 1% by weight Ethanol 30% by weight Propyl parahydroxybenzoate 0.3% by weight Fragrance 0.3% by weight water remainder Total 100% by weight

[0080] <Formulation example 10: Antiperspirant cream> Any of the lactone compound combinations listed in Table 1 Benzalkonium chloride 0.07% by weight Isopropylmethylphenol 0.07% by weight Aluminum chlorohydrate 4% by weight Cyclopentasiloxane 25% by weight Alkyl polyacrylate 6% by weight POE·POP dimethicone copolymer 3.5% by weight Dipotassium glycyrrhizinate 0.05% by weight Concentrated glycerin 7% by weight Isononyl isononanoate 5% by weight Sorbitan isostearate 5% by weight l-Menthol 0.5% by weight Fragrance 0.3% by weight water remainder Total 100% by weight

[0081] <Formulation Example 11: Antiperspirant Gel> Any of the lactone compound combinations listed in Table 1 Benzalkonium chloride 0.06% by weight Isopropylmethylphenol 0.05% by weight Aluminum chlorohydrate 8% by weight Magnesium aluminometasilicate 0.5% by weight Dipropylene glycol 10% by weight Polyoxypropylene glycol 0.5% by weight Hydroxypropyl methylcellulose 0.5% by weight Xanthan gum 0.5% by weight Ethanol 10% by weight l-Menthol 0.3% by weight l-menthyl glyceryl ether 0.3% by weight Peppermint oil 0.3% by weight Fragrance 0.3% by weight water remainder Total 100% by weight

[0082] <Formulation example 12: Antiperspirant spray> Any of the lactone compound combinations listed in Table 1 Isopropylmethylphenol 0.1% by weight Zinc paraphenolsulfonate 1% by weight Diethyl sebacate 4% by weight Talc 5% by weight Nylon powder 1% by weight Fragrance 0.5% by weight Ethanol 15% by weight Dimethyl ether Remainder Total 100% by weight

[0083] <Formulation example 13: Antiperspirant roll-on> Any of the lactone compound combinations listed in Table 1 Benzalkonium chloride 0.06% by weight Isopropylmethylphenol 0.06% by weight Zinc paraphenolsulfonate 5% by weight Butylene glycol 5% by weight Aluminum chlorohydrate 0.05% by weight Talc 3% by weight Nylon powder 0.5% by weight Cetyltrimethylammonium bromide solution 1% by weight Hydroxypropyl methylcellulose 0.5% by weight l-Menthol 0.1% by weight Fragrance 0.3% by weight Water 40% by weight Ethanol Remainder Total 100% by weight

[0084] <Formulation example 14: Antiperspirant mist> Any of the lactone compound combinations listed in Table 1 Benzalkonium chloride 0.05% by weight Isopropylmethylphenol 0.06% by weight Zinc paraphenolsulfonate 1% by weight Butylene glycol 5% by weight Aluminum chlorohydrate 0.02% by weight Sericite composite 0.3% by weight Cetyltrimethylammonium bromide solution 0.5% by weight l-Menthol 0.3% by weight Fragrance 0.3% by weight Water 10% by weight Ethanol Remainder Total 100% by weight

[0085] <Formulation Example 15: Antiperspirant Stick> Any of the lactone compound combinations listed in Table 1 Benzalkonium chloride 0.055% by weight Isopropylmethylphenol 0.05% by weight Aluminum chlorohydrate 5% by weight Polyethylene wax 5% by weight Microcrystalline wax 5% by weight Glyceryl monostearate 3% by weight Isononyl isononanoate 5% by weight Talc 12% by weight Methylpolysiloxane 2% by weight Decamethylpentasiloxane 0.3% by weight Silylated anhydrous silica 15% by weight Cetyl alcohol 2% by weight Hydroxyapatite 0.3% by weight Cetyltrimethylammonium bromide solution 0.5% by weight l-Menthol 0.5% by weight Zinc oxide 0.3% by weight Fragrance 0.3% by weight Stearyl alcohol balance Total 100% by weight

[0086] <Formulation example 16: Wipe-off lotion> Any of the lactone compound combinations listed in Table 1 Ethanol 15% by weight Polyoxyethylene Polyoxypropylene Decyl Tetradecyl Ether 1% by weight Hydrolyzed jojoba esters 0.01% by weight Methylsiloxane network polymer 0.01% by weight Magnesium ascorbyl phosphate 0.3% by weight Fragrance 0.05% by weight Paraben 0.3% by weight Citric acid (appropriate amount) Purified water remainder Total 100% by weight

[0087] <Formulation Example 17: Deodorant Sheet> Any of the lactone compound combinations listed in Table 1 Isopropylmethylphenol 0.05% by weight Zinc paraphenolsulfonate 1% by weight Ethanol 30% by weight Cetyltrimethylammonium bromide solution 0.5% by weight Butylene glycol 1% by weight Sericite composite 0.1% by weight Kaolin 0.3% by weight Phenoxyethanol 0.1% by weight Fragrance 0.1% by weight Citric acid (appropriate amount) Purified water remainder Total 100% by weight

[0088] <Formulation example 18: Bath milk> Any of the lactone compound combinations listed in Table 1 Polysorbate 20 12% by weight Polysorbate 80 3% by weight Octyldodecanol 5% by weight Sunflower oil 2% by weight Pigments / Fragrances Appropriate amount Mineral oil remainder Total 100% by weight

[0089] <Formulation example 19: Powdered bath additives> Any of the lactone compound combinations listed in Table 1 Sodium bicarbonate 20% by weight Sodium sulfate 20% by weight Sodium chloride 5% by weight Pigments / Fragrances Appropriate amount Sodium carbonate remainder Total 100% by weight

[0090] <Formulation example 20: Tablet-type bath additives> Any of the lactone compound combinations listed in Table 1 Sodium bicarbonate 10% by weight Sodium carbonate 13% by weight Succinic acid 25% by weight Polyethylene glycol 1% by weight Pigments / Fragrances Appropriate amount Sodium sulfate remainder Total 100% by weight [Industrial Applicability]

[0091] According to the present invention, it is possible to provide an epidermal keratinocyte proliferation promoter, a skin turnover promoter, and a skin metabolism promoter that can prevent / ameliorate the decline in skin metabolic function and the slowdown in epidermal turnover rate caused by various factors such as aging and damage caused by ultraviolet rays, and the resulting deterioration of the skin environment, thereby preventing skin aging phenomena such as fine wrinkles, dullness, and pigmentation, as well as body odor and head odor (including scalp odor), which are thought to be caused in part by an imbalance of resident bacteria due to a deterioration of the skin environment. These accelerators of the present invention have the effect of promoting epidermal keratinocyte proliferation, the effect of promoting skin turnover, the effect of restoring the metabolic function of the skin, or the effect of preventing and / or improving at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of skin texture, loss of firmness, pigmentation, skin tone reduction, rough skin, skin odour due to aging, and head odour (including scalp odour), and are therefore suitable for use in external skin compositions such as cosmetics and quasi-drugs that are expected to have such effects.

Claims

1. An epidermal keratinocyte proliferation promoter, characterized by containing a lactone compound represented by the following formula (I) as an active ingredient: 【Chemistry 8】 (wherein R is an alkyl group having 2 to 9 carbon atoms).

2. A skin turnover promoter characterized by containing a lactone compound represented by the following formula (I) as an active ingredient: 【Chemistry 9】 (wherein R is an alkyl group having 2 to 9 carbon atoms).

3. A skin metabolism promoter comprising a lactone compound represented by the following formula (I) as an active ingredient: 【Chemistry 10】 (wherein R is an alkyl group having 2 to 9 carbon atoms).

4. The enhancer according to any one of claims 1 to 3, which is used to prevent and / or improve at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of texture, loss of firmness, pigmentation, skin tone loss, rough skin, skin odour due to aging, and scalp odour.

5. The enhancer according to any one of claims 1 to 4, which is for external use.

6. A composition for external application to the skin containing the promoter according to any one of claims 1 to 4 for promoting epidermal keratinocyte proliferation, promoting skin turnover, restoring the metabolic function of the skin, or preventing and / or improving at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of skin texture, loss of firmness, pigmentation, skin tone loss, rough skin, skin odour due to aging, and scalp odour.

7. A method for promoting proliferation of epidermal keratinocytes, comprising using a lactone compound represented by the following formula (I): 【Chemistry 11】 (wherein R is an alkyl group having 2 to 9 carbon atoms).

8. A method for promoting skin turnover, comprising using a lactone compound represented by the following formula (I): 【Chemistry 12】 (wherein R is an alkyl group having 2 to 9 carbon atoms).

9. A method for promoting skin metabolism, characterized by using a lactone compound represented by the following formula (I): 【Chemistry 13】 (wherein R is an alkyl group having 2 to 9 carbon atoms).

10. The method for promoting skin aging described in any one of claims 7 to 9 is used to prevent and / or improve at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of texture, loss of firmness, pigmentation, skin tone loss, rough skin, skin irritation, body odor, and scalp odor.

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