JP7706919B2 - EPIDERMAL KERATINOCYTE PROLIFERATION PROMOTER, SKIN TURNOVER PROMOTER, SKIN METABOLISM PROMOTER, EXTERNAL SKIN COMPOSITION, EPIDERMAL KERATINOCYTE PROLIFERATION PROMOTER METHOD, SKIN TURNOVER PROMOTER METHOD, AND SKIN METABOLISM PROMOTER METHOD - Google Patents

Description

The present invention relates to an epidermal keratinocyte proliferation promoter, a skin turnover promoter, a skin metabolism promoter, a skin topical composition, a method for promoting epidermal keratinocyte proliferation, a method for promoting skin turnover, and a method for promoting skin metabolism.

Skin is a layered tissue that covers our body and creates a boundary with the outside world. This skin is composed of four layers, starting from the basal layer, which is the lowest layer, followed by the spinous layer, granular layer, and stratum corneum. Most of the cells in each layer are keratinocytes that have differentiated from the basal layer. Keratinocytes that divide and proliferate in the basal layer differentiate into keratinocytes as they pass through the spinous layer and granular layer, forming the stratum corneum composed of keratin protein fibers with strong cross-linking, and finally fall off from the stratum corneum as scum. In normal skin, the stratum corneum, which is the outermost layer, acts as a barrier, preventing the skin from losing moisture more than necessary and preventing the intrusion of foreign substances such as bacteria and harmful substances from the outside world (see Non-Patent Documents 1 and 2). In order to maintain this barrier function in the skin, the cycle (keratinization) from when keratinocytes are produced in the basal layer to when they become scum and fall off is usually repeated in a four-week cycle (skin turnover), and the metabolism of the epidermis is carried out.

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 and the turnover rate of the epidermis slows down (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 poor excretion of melanin, causing pigmentation and dull skin (see Non-Patent Documents 2 and 3).

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 believed to improve skin conditions such as fine wrinkles, dullness, and pigmentation. Regarding substances that have an epidermal keratinocyte proliferation promoting effect, for example, there have been reports that some herbal medicines have an epidermal keratinocyte proliferation promoting effect (see Non-Patent Document 4). In addition, an epidermal keratinocyte proliferation promoting agent is known that contains an extract of the germ found in the seeds of lotus (Nelumbo nucifera Gaertn.) of the Nelumbo genus of the Nymphaeaceae family as an active ingredient (see Patent Document 1). However, the active ingredient of these substances that have an epidermal keratinocyte proliferation promoting effect has not been identified. In addition, tranexamic acid or its derivatives (see Patent Document 2), arbutin (see Patent Document 3), etc. are known to have epidermal keratinocyte proliferation activity and the active ingredient has been identified.

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. In addition to their fragrance properties, lactones are known to have functions against odors, such as suppressing the smell of dampness, scalp odor, and other unpleasant odors (see Patent Documents 4 to 6), and improving body odor (see Patent Document 7). As for other pharmacological effects of lactones, it has been shown that γ-decanolactone has anticonvulsant properties in a mouse experimental model (see Non-Patent Document 5), but no other effects are known.

JP 2002-68993 A JP 2015-34155 A JP 2011-173831 A JP 2015-221956 A JP 2015-151531 A JP 2015-193643 A JP 2015-131825 A

Cosmetic Technology Journal, Vol. 23, No. 1, 1989 Production Research, 59, 124-127, 2007 J Gerontol. , 38(2), 137-42, 1983 Japanese Journal of Traditional Chinese Medicine, Vol. 15, p. 426-427, 1998 J Ethnopharmacology, 58, No. 3, 175-81, 1997

The present invention has been made in view of such circumstances, and the object of the present invention is to provide a preparation that can prevent/ameliorate the deterioration of the skin environment caused by the decline in the skin's metabolic function and the slowing of epidermal turnover rate, which are caused by various factors such as aging and damage caused by ultraviolet rays, and thereby prevent/ameliorate the so-called skin aging phenomena such as fine wrinkles, dullness, loss of texture, loss of firmness, pigmentation, lighter skin tone, stiff skin, rough skin, 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.

As a result of intensive research conducted by the inventors to solve the above problems, they discovered that lactones, which have been widely used as fragrances, have the function of promoting the proliferation of epidermal keratinocytes, and thus completed the present invention. That is, the gist of the present invention is as follows.

（式中、Ｒは、炭素数２～９のアルキル基である。）
［２］下記式（Ｉ）で表されるラクトン化合物を有効成分として含むことを特徴とする、皮膚ターンオーバー促進剤。

（式中、Ｒは、炭素数２～９のアルキル基である。）
［３］下記式（Ｉ）で表されるラクトン化合物を有効成分として含むことを特徴とする、皮膚新陳代謝促進剤。

（式中、Ｒは、炭素数２～９のアルキル基である。）
［４］皮膚の小じわ、くすみ、キメの消失、ハリの低下、色素沈着、肌のトーンダウン、肌のごわつき、肌荒れ、加齢臭、頭臭から成る群より選択される少なくとも１種の症状を予防及び／又は改善するために用いられる、［１］～［３］のいずれかに記載の促進剤。
［５］外用である、［１］から［４］のいずれかに記載の促進剤。
［６］［１］から［４］のいずれかに記載の促進剤を含有する、表皮角化細胞増殖促進用、皮膚ターンオーバー促進用、皮膚の新陳代謝機能回復用、又は、皮膚の小じわ、くすみ、キメの消失、ハリの低下、色素沈着、肌のトーンダウン、肌のごわつき、肌荒れ、加齢臭、頭臭から成る群より選択される少なくとも１種の症状の予防及び／若しくは改善用の皮膚外用組成物。
［７］下記式（Ｉ）で表されるラクトン化合物を使用することを特徴とする、表皮角化細胞増殖促進方法。

（式中、Ｒは、炭素数２～９のアルキル基である。）
［８］下記式（Ｉ）で表されるラクトン化合物を使用することを特徴とする、皮膚ターンオーバー促進方法。

（式中、Ｒは、炭素数２～９のアルキル基である。）
［９］下記式（Ｉ）で表されるラクトン化合物を使用することを特徴とする、皮膚新陳代謝促進方法。

（式中、Ｒは、炭素数２～９のアルキル基である。）
［１０］皮膚の小じわ、くすみ、キメの消失、ハリの低下、色素沈着、肌のトーンダウン、肌のごわつき、肌荒れ、加齢臭、頭臭から成る群より選択される少なくとも１種の症状を予防及び／又は改善するために用いられる、［７］～［９］に記載の促進方法。 [1] An epidermal keratinocyte proliferation promoter, comprising a lactone compound represented by the following formula (I) as an active ingredient:

(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):

(In the formula, R is an alkyl group having 2 to 9 carbon atoms.)
[3] A skin metabolism enhancer comprising a lactone compound represented by the following formula (I) as an active ingredient:

(In the formula, R is an alkyl group having 2 to 9 carbon atoms.)
[4] The accelerator according to any one of [1] to [3], which is used for preventing and/or improving 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, body odor, and head odor.
[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 elasticity, pigmentation, reduced skin tone, stiff skin, rough skin, body odor, and head odor.
[7] A method for promoting proliferation of epidermal keratinocytes, comprising using a lactone compound represented by the following formula (I):

(In the formula, 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):

(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):

(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, body odor, and head odor.

According to the present invention, it is possible to provide an epidermal keratinocyte proliferation promoter, skin turnover promoter, and skin metabolism promoter that can prevent/ameliorate the decline in the metabolic function of the skin, the slowdown in the rate of epidermal turnover, and the resulting deterioration of the skin environment, which are caused by various factors such as aging and damage caused by ultraviolet rays, thereby preventing skin aging phenomena such as fine wrinkles, dullness, and pigmentation, 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. These promoters 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, aging odor, and head odor (including scalp odor), and are therefore suitable for use in external skin compositions such as cosmetics and quasi-drugs that are expected to have such effects.

FIG. 1 shows the proliferation-promoting effect of lactones on human epidermal keratinocytes.

The present invention will be described in detail below. Note that the terms used in this specification are to be interpreted as having the meanings normally used in the relevant technical field unless otherwise specified.

[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. The epidermal keratinocyte proliferation promoter of the present invention contains the above-mentioned lactone compound, and thus has the effect of promoting the proliferation of epidermal keratinocytes of the skin, thereby promoting the turnover of the skin and restoring the metabolic function of the skin. It is believed that when the turnover of the skin slows down due to aging or other causes, the discharge of melanin becomes poor, and pigmentation and dullness are more likely to occur. In addition, it is believed that when the metabolism of the skin deteriorates, the skin environment deteriorates and the balance of normal bacteria on the skin (including the scalp) is disrupted, and bacteria that cause odor increase, leading to the occurrence of aging odor, head odor, etc. Therefore, when the turnover of the skin is promoted by the epidermal keratinocyte proliferation promoter of the present invention, pigmentation and dullness can be suppressed and the melanin discharge function can be improved, and the skin tone-up effect, improvement of skin transparency, and improvement of skin luster can be expected. In addition, it is also possible to prevent/ameliorate skin troubles such as fine wrinkles, loss of skin texture, loss of firmness, rough skin, and skin troubles such as body odor due to aging, head odor, and the like. That is, the epidermal keratinocyte proliferation 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 down, rough skin, skin trouble due to aging, and head odor. In this specification, head odor is a concept that also includes scalp odor.

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.

Specific examples of lactone compounds represented by the above formula (I) include, for example, 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, and γ-decalactone and γ-undecalactone are 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 kinds.

The content of the lactone compound represented by formula (I) contained in the epidermal keratinocyte proliferation promoter of the present invention is 0.0000001% by weight to 10% by weight, and from the viewpoint of the epidermal keratinocyte proliferation promoting effect, it is preferably 0.0000005% by weight to 5% by weight, more preferably 0.000001% by weight to 3% by weight, even more preferably 0.000005% by weight to 2% by weight, and particularly preferably 0.00001% by weight to 1% by weight. In addition, when the compound is used after dilution, such as in bath additives, the content of the lactone compound can be adjusted taking into consideration 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. In addition, when two or more lactone compounds are used in combination, the total amount is within the above numerical range.

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 described below.

The epidermal keratinocyte proliferation promoter of the present invention may consist of the lactone compound alone, or may be formulated by blending the lactone compound with ingredients necessary for formulation. When formulated, it can be made into any dosage form such as powder, granules, tablets, liquid, etc., using a pharma- ceutically acceptable base material, carrier, and any other additives according to conventional methods. The epidermal keratinocyte proliferation promoter of the present invention itself can be used as an external preparation, ointment, patch, etc., and, as described below, the epidermal keratinocyte proliferation promoter can also be blended with other compositions such as an external skin composition for use.

<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 formulation forms by mixing 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 as necessary.

(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 methylpolysiloxane, highly polymerized methylpolysiloxane, 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, meu wax, candelilla wax, and lanolin; higher alcohols such as cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, octyldodecanol, isostearyl alcohol, phytosterol, and cholesterol; cellulose derivatives such as ethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methylcellulose; Examples of the polysaccharides include 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; and water.

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. The amounts used are appropriately selected from the ranges known to those skilled in the art.

(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 luster imparting agents, dispersants, chelating agents, pH adjusters, preservatives, thickeners, irritation reducers, etc., 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.

The surfactant may be any of nonionic surfactants, cationic surfactants, anionic surfactants, amphoteric surfactants, etc., and examples thereof include sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexyl acid, and diglycerol sorbitan tetra-2-ethylhexyl acid; 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 such surfactants include polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan monostearate (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 surfactants such as polyoxyethylene-methylpolysiloxane copolymers, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone.

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

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

Examples of the coloring agents include inorganic pigments, natural dyes, etc.

Examples of the pearlescent luster imparting agent include ethylene glycol distearate, ethylene glycol monostearate, triethylene glycol distearate, etc.

Examples of the dispersing agent include sodium pyrophosphate, sodium hexametaphosphate, polyvinyl alcohol, polyvinylpyrrolidone, methyl vinyl ether/maleic anhydride crosslinked copolymer, organic acids, etc.

Examples of the chelating agent include EDTA disodium salt, EDTA calcium disodium salt, etc.

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.).

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.

Examples of the thickening agents include vinyl thickening agents such as polyvinyl alcohol, polyvinylpyrrolidone, and carboxyvinyl polymers; cellulose thickening agents such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and carboxyethylcellulose; 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/Na acryloyldimethyltaurate) copolymer, (ammonium acryloyldimethyltaurate/vinylpyrrolidone) copolymer, and the like.

Examples of the irritation reducers include licorice extract, sodium alginate, gum arabic, polyvinylpyrrolidone, etc.

(Form of preparation)
The formulation of the epidermal keratinocyte proliferation promoter of the present invention is not particularly limited, and examples thereof include skin care products (lotion, milky lotion, serum, cream, etc.), cosmetics for makeup, cosmetics for base, body soap, cleansing agents such as face wash, shampoo, treatment, dry shampoo, scalp care agent, hair mist, hair care agents such as hair growth agents and hair growth agents, cleansing agents, wipe-off lotions, deodorants, antiperspirants, bath agents, ointments, liquids, suspensions, emulsions (milky lotions and creams), gels, liniments, lotions, poultices, mists, aerosols, powders, granules, tablets (including effervescent tablets), solid soaps, etc. Among these, liquid to semi-solid formulations are preferred, and it is particularly useful to apply them to liquids, lotions, ointments, gels, and emulsions. These formulations can be produced according to conventional methods, such as the methods described in the General Provisions for Preparations of the 17th Revised Japanese Pharmacopoeia. They may also be used by impregnating nonwoven fabrics. The epidermal keratinocyte proliferation promoter of the present invention is particularly suitable for use as an external preparation for anti-aging purposes.

[Skin turnover promoter]
The skin turnover promoter of the present invention is characterized by containing the lactone compound represented by the above formula (I) as an active ingredient. The skin turnover promoter of the present invention contains the above lactone compound, which has the effect of promoting the proliferation of epidermal keratinocytes of the skin, thereby promoting the turnover of the skin and promoting the metabolic function of the skin. It is believed that when the turnover of the skin slows down due to aging or other causes, the discharge of melanin becomes poor, and pigmentation and dullness are easily caused. In addition, it is believed that when the metabolism of the skin declines, the skin environment deteriorates, the balance of the resident bacteria on the skin (including the scalp) is disrupted, and the bacteria that cause odor increase, leading to the occurrence of aging odor, head odor, etc. Therefore, when the turnover of the skin is promoted by the skin turnover promoter of the present invention, pigmentation and dullness can be suppressed and the melanin discharge function can be improved, and the skin tone-up effect, improvement of the skin transparency, and improvement of the skin luster can be expected. It is also possible to prevent/improve skin troubles such as fine wrinkles, loss of skin texture, loss of firmness, rough skin, and skin odor associated with aging, head odor, and the like. That is, the skin turnover promoter of the present invention is suitably used for 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 down, rough skin, rough skin, skin odor associated with aging, and head odor. The specific explanation of the skin turnover promoter of the present invention can be applied as it is by replacing the epidermal keratinocyte proliferation promoter in the explanation of the epidermal keratinocyte proliferation promoter of the present invention described above with the skin turnover promoter in the description of the epidermal keratinocyte proliferation promoter of the present invention.

[Skin metabolism promoter]
The skin metabolism promoter of the present invention is characterized by containing the lactone compound represented by the above formula (I) as an active ingredient. The skin metabolism promoter of the present invention contains the above lactone compound, which has the effect of promoting the proliferation of epidermal keratinocytes of the skin, thereby promoting the turnover of the skin and promoting the metabolic function of the skin. It is believed that when the turnover of the skin slows down and the metabolic function of the skin declines due to aging or other causes, the discharge of melanin becomes poor, and pigmentation and dullness are likely to occur. Therefore, when the metabolic function of the skin is promoted by the skin metabolism promoter of the present invention, pigmentation and dullness can be suppressed and the melanin discharge function can be improved, and the skin tone-up effect, improvement of the skin transparency, and improvement of the skin luster can be expected. In addition, it is believed that when the metabolism of the skin declines, the skin environment deteriorates, the balance of normal bacteria on the skin (including the scalp) is disrupted, and bacteria that cause odor increase, leading to the occurrence of aging odor, head odor, etc. It is also possible to prevent/improve skin troubles such as fine wrinkles, loss of skin texture, loss of firmness, rough skin, and skin odor associated with aging, head odor, and the like. That is, the skin metabolism promoter of the present invention is suitably used for 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 down, rough skin, rough skin, skin odor associated with aging, and head odor. The specific explanation of the skin metabolism promoter of the present invention can be applied as it is by replacing the epidermal keratinocyte proliferation promoter in the explanation of the epidermal keratinocyte proliferation promoter of the present invention described above with the skin metabolism promoter in the description of the epidermal keratinocyte proliferation promoter of the present invention.

[Skin external composition]
The epidermal keratinocyte proliferation promoter, skin turnover promoter, and skin metabolism promoter of the present invention can be blended with other compositions and used as a skin external composition. The present invention also includes a skin external composition containing the above-mentioned epidermal keratinocyte proliferation promoter, skin turnover promoter, or skin metabolism promoter of the present invention. The skin external composition of the present invention contains the epidermal keratinocyte proliferation promoter, skin turnover promoter, or skin metabolism promoter of the present invention, and thus exhibits an epidermal keratinocyte proliferation promoting effect, a skin turnover promoting effect, and a skin metabolism promoting effect, and is therefore suitably used for preventing and/or improving at least one symptom selected from the group consisting of fine wrinkles, dullness, loss of texture, loss of firmness, pigmentation, skin tone down, stiff skin, rough skin, aging odor, and head odor.

The topical skin composition of the present invention may contain the following optional ingredients 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 described above, within the scope of not impairing the effects of the present invention.

Optional components that may be contained in the topical skin composition of the present invention in addition to the above essential components include, for example, anti-inflammatory agents, cooling agents, germicides, vitamins, organic acids, moisturizing components, polyhydric alcohols, scrubbing agents, UV absorbing components, UV scattering components, astringent components, peptides or derivatives thereof, amino acids or derivatives thereof, cleansing components, keratin softening components, cell activating components (excluding lactones in the present invention), anti-aging components (excluding lactones in the present invention), blood circulation promoting components, whitening components, powders, etc. In the topical skin composition of the present invention, each of these components may be used alone or in combination of two or more types.

Examples of anti-inflammatory agents include allantoin and its derivatives, glycyrrhetinic acid and its derivatives, glycyrrhizic acid and its derivatives, salicylic acid derivatives, aminocaproic acid, azulene and its derivatives, zinc oxide, tocopherol acetate, hydrocortisone, prednisolone, and salts thereof. Among them, allantoin, aluminum chlorhydroxyl allantoin, aluminum dihydroxyl allantoin, glycyrrhetinic acid, glycyrrhizic 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, and phosphoric acid, salts of organic acids such as maleic acid and methanesulfonic acid, alkali metal salts such as sodium and potassium, alkaline earth metal salts, and ammonium salts.

Examples of the cooling agents 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.

Examples of the above 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.

The vitamins may be either water-soluble or oil-soluble, for example, vitamin B6 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-panthesine, D-pantethine, coenzyme A, pantothenyl ethyl ether, and salts thereof; nicotinic acid, dl-α-tocopherol nicotinate, benzyl nicotinate, methyl nicotinate, β-butoxyethyl nicotinate, 1-(4-methyl nicotinate), ... nicotinic acids such as nicotinamide and salts thereof; vitamin B1s such as 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 nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine diphosphate hydrochloride, and thiamine triphosphate monophosphate); riboflavin, flavin mononucleotide, flavin a Vitamin B2 such as denine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin sodium 5'-phosphate, riboflavin tetranicotinate, and salts thereof; biotins such as biotin, biocytin, and salts thereof; folates such as folic acid, pteroylglutamic acid, and salts thereof; vitamin B12 such as cyanocobalamin, hydroxocobalamin, deoxyadenosylcobalamin, and salts thereof; ascorbic acid, dehydroascorbic acid, ascorbic acid phosphate, ascorbic acid-2-glucoside, 3-O-ethyl ascorbic acid, and salts thereof (for example, ascorbic acid sodium salt, water-soluble vitamin C such as dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate; oil-soluble vitamin C such as ascorbigen-A, ascorbyl stearate, ascorbyl palmitate, L-ascorbyl dipalmitate, and ascorbyl tetra-2-hexyldecanoate; vitamin D such as ergocalciferol and cholecalciferol; vitamin K such as phylloquinone and farnoquinone; and vitamin-like factors such as ferulic acid.

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.

Examples of the moisturizing ingredients 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 pyrrolidone carboxylate; lipids such as ceramide, cholesterol, and phospholipids; and plant extracts such as chamomile extract, witch hazel extract, tea extract, and perilla extract.

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.

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, hazel shell powder, polyethylene powder, anhydrous silicic acid, etc.

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

Examples of the ultraviolet scattering components include inorganic compounds such as hydrous silicic acid, zinc silicate, cerium silicate, titanium silicate, zirconium oxide, cerium oxide, titanium oxide, iron oxide, and anhydrous silicic acid, and these inorganic compounds are coated with inorganic powders such as hydrous silicic acid, aluminum hydroxide, mica, and talc, or are composited with resin powders such as polyamide, polyethylene, polyester, polystyrene, and nylon, and further treated with silicone oil, aluminum salt of fatty acid, etc.

Examples of the astringent ingredients include zinc sulfate, aluminum chloride, zinc sulfocarbonate, tannic acid, etc.

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, acylated peptides (palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide, etc.), etc.

Examples of the above 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, creatine, etc.

Examples of the cleaning components 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 carboxylates 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 dimethylaminoacetate betaine, lauryl dimethylaminoacetate betaine, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, lauryl hydroxysulfobetaine, and sodium lauroyl amidoethyl hydroxyethyl carboxymethyl betaine hydroxypropyl phosphate; and amino acid amphoteric surfactants such as sodium lauryl aminopropionate.

Examples of the keratin softening ingredients include lactic acid, salicylic acid, gluconic acid, citric acid, malic acid, fruit acid, phytic acid, urea, sulfur, etc.

The above-mentioned cell activation components include, for example, 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, saponin, photosensitizer No. 301, etc.

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

The above blood circulation promoting ingredients include ingredients derived from plants (e.g., ginseng, angelica, arnica, ginkgo, fennel, Japanese oak, 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, red pepper, angelica tree, tonin, spruce, carrot, garlic, butcher's broom, grape, peony, horse chestnut, melissa, yuzu, coix seed, ryokucha, rosemary, rose hip, tangerine peel, angelica tree, spruce, peach, apricot, walnut, corn, etc.); acetylcholine, ichthammol, cantharides tincture, gamma oryzanol, cepharanthine, tolazoline, tocopherol nicotinate, glucosyl hesperidin, etc.

Examples of the whitening ingredients include tocopherol and tranexamic acid.

Examples of the powder components include aluminum starch octenyl succinate, talc, corn starch, magnesium hydroxide, anhydrous silicic acid, light anhydrous silicic acid, mica, hydroxyapatite, zinc oxide, titanium oxide, nylon powder, and charcoal.

(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.

<Method of manufacturing the composition for external 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 components (the above-mentioned optional components, base or carrier, additives, etc.) necessary for producing an epidermal keratinocyte proliferation promoter containing the lactone compound represented by the above formula (I) as an essential component, a skin turnover promoter or a skin metabolism promoter, and a skin topical composition. For the above-mentioned base or carrier and additives, please refer to the explanation in the section on skin keratinocyte proliferation promoter.

<Uses of topical skin composition>
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 thus exerts the effects of promoting epidermal keratinocyte proliferation, promoting skin turnover, and promoting skin metabolism, and is therefore suitably used for 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, reduced skin tone, stiff skin, rough skin, aging odor, and head odor. The skin topical composition of the present invention used for such purposes can be used, for example, as skin care products (lotion, milky lotion, serum, cream, etc.), cosmetics for makeup, cosmetics for base, cleansing agents such as body soap and face wash, shampoo, treatment, dry shampoo, scalp care agent, hair mist, hair care agents such as hair growth agents and hair growth agents, cleansing agents, deodorants, antiperspirants, ointments, liquids, suspensions, emulsions (milky lotions and creams), gels, liniments, lotions, poultices, mists, aerosols, powders, granules, solid soaps, etc. In particular, it is preferably used as a skin topical composition for anti-aging purposes.

[Method for promoting proliferation of epidermal keratinocytes, 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, which are characterized by using a lactone compound represented by the above formula (I). The above lactone compound has the effect of promoting the proliferation of epidermal keratinocytes of the skin, thereby promoting the turnover of the skin and restoring the metabolic function of the skin. It is believed that when the turnover of the skin slows down due to aging or other causes, the discharge of melanin becomes poor, and pigmentation and dullness are more likely to occur. In addition, it is believed that when the metabolism of the skin deteriorates, the skin environment deteriorates, the balance of normal bacteria on the skin (including the scalp) is disrupted, and bacteria that cause odor increase, leading to the occurrence of aging odor, head odor, etc. Therefore, when the turnover of the skin is promoted by the method of the present invention, pigmentation and dullness can be suppressed and the melanin discharge function can be improved, and the skin tone-up effect, improvement of skin transparency, and improvement of skin luster can be expected. In addition, it is also possible to prevent/ameliorate skin troubles such as fine wrinkles, loss of skin texture, loss of firmness, rough skin, and the like, as well as body odor due to aging, head odor, etc. 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 down, rough skin, rough skin, body odor due to aging, and head odor.

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 composition for topical use on the skin 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 composition for topical use on the skin 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 composition for topical use on the skin containing the same.

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

[Human epidermal keratinocyte proliferation test]
Normal human epidermal keratinocytes (NHEK, Kurabo) were put to sleep, then seeded in a 75 ^cm2 flask (FALCON) at the recommended seeding density, and cultured for 3 days under 37 ° C, 5% _CO2 conditions. After that, the cells were collected using 0.025% Trypsin-EDTA (Kurabo), and then seeded and cultured at the set cell density on various plates for use in the test. NHEK was seeded on a 96-well black plate (Corning) at 5,000 cells/200 μL/well, and after 24 hours of culture, the medium was removed by suction, and various lactones diluted to 0.000001% in the medium were added at 200 μL/well, and further cultured for 3 days. After the incubation, the medium was removed, and Hoechst 33342 (DOJINDO) diluted 1/1,000 was added and incubated for 5 minutes in the dark. The stained nuclei were counted using ImageXpress (Molecular Device) to obtain the cell number. The results are shown in FIG. 1.

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 is not shown, it was confirmed that the proliferation-promoting effect of human epidermal keratinocytes was obtained even at concentrations of 0.0000001% and 0.00000001% of various lactones.

The following are examples of formulations of the topical compositions of the present invention. The numerical values (%) of each lactone in Table 1 indicate the final concentration (wt%) in the entire composition when each combination is used in each formulation example.

<Formulation Example 1: Body soap>
Any of the combinations of lactone compounds 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 balance total 100% by weight

<Formulation Example 2: Foam-type body wash>
Any of the combinations of lactone compounds listed in Table 1 PEG-80 sorbitan laurate 5% by weight
Disodium cocoyl glutamate 4% by weight
Sodium cocoyl glycine 2% by weight
Sorbitol 5% by weight
Cocoyl methyl taurine 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 balance total 100% by weight

<Formulation Example 3: Facial cleanser>
Any of the combinations of lactone compounds 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 balance total 100% by weight

<Formulation Example 4: Shampoo>
Any of the combinations of lactone compounds listed in Table 1 Sodium laureth sulfate 30% by weight
Triethanolamine cocoyl glutamate 5% by weight
Sodium lauroyl methylalanine 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 balance total 100% by weight

<Formulation Example 5: Shampoo>
Any of the combinations of lactone compounds 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 balance total 100% by weight

Formulation Example 6: Hair Conditioner
Any of the combinations of lactone compounds 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
Cetanol 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 balance total 100% by weight

Formulation Example 7: Hair Treatment
Any combination of lactone compounds 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 pentastriate 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 paraoxybenzoate 0.3% by weight
EDTA-2Na 0.05% by weight
Fragrance 0.5% by weight
Water balance total 100% by weight

Formulation Example 8: Hair Essence
Any of the combinations of lactone compounds 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 balance total 100% by weight

<Formulation Example 9: Hair Mist>
Any of the combinations of lactone compounds 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 paraoxybenzoate 0.3% by weight
Fragrance 0.3% by weight
Water balance total 100% by weight

Formulation Example 10: Antiperspirant Cream
Any of the combinations of lactone compounds listed in Table 1 Benzalkonium chloride 0.07% by weight
Isopropylmethylphenol 0.07% by weight
Aluminum chlorohydrate 4% by weight
Cyclopentasiloxane 25% by weight
Polyalkyl acrylate 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 balance total 100% by weight

Formulation Example 11: Antiperspirant Gel
Any of the combinations of lactone compounds 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 balance total 100% by weight

Formulation Example 12: Antiperspirant Spray
Any of the combinations of lactone compounds 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

<Formulation Example 13: Antiperspirant Roll-on>
Any of the combinations of lactone compounds 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 Balance Total 100% by weight

Formulation Example 14: Antiperspirant Mist
Any of the combinations of lactone compounds 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 liquid 0.5% by weight
l-Menthol 0.3% by weight
Fragrance 0.3% by weight
Water 10% by weight
Ethanol Balance Total 100% by weight

Formulation Example 15: Antiperspirant Stick
Any of the combinations of lactone compounds 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 silicic acid 15% by weight
Cetanol 2% by weight
Hydroxyapatite 0.3% by weight
Cetyltrimethylammonium bromide liquid 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

Formulation Example 16: Wipe-off lotion
Any of the combinations of lactone compounds 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 balance total 100% by weight

Formulation Example 17: Deodorant Sheet
Any of the combinations of lactone compounds listed in Table 1 Isopropylmethylphenol 0.05% by weight
Zinc paraphenolsulfonate 1% by weight
Ethanol 30% by weight
Cetyltrimethylammonium bromide liquid 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 balance total 100% by weight

<Formulation Example 18: Bath Milk>
Any of the combinations of lactone compounds listed in Table 1 Polysorbate 20 12% by weight
Polysorbate 80 3% by weight
Octyldodecanol 5% by weight
Sunflower oil 2% by weight
Coloring and fragrance: appropriate amount Mineral oil Remainder Total: 100% by weight

<Formulation Example 19: Powder-type bath additive>
Any of the combinations of lactone compounds listed in Table 1 Sodium bicarbonate 20% by weight
Sodium sulfate 20% by weight
Sodium chloride 5% by weight
Coloring and fragrance Appropriate amount Sodium carbonate Remainder Total 100% by weight

<Formulation Example 20: Tablet-type bath additive>
Any of the combinations of lactone compounds 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 Balance Total 100% by weight

According to the present invention, it is possible to provide an epidermal keratinocyte proliferation promoter, skin turnover promoter, and skin metabolism promoter that can prevent/ameliorate the decline in the metabolic function of the skin, the slowdown in the rate of epidermal turnover, and the resulting deterioration of the skin environment, which are caused by various factors such as aging and damage caused by ultraviolet rays, thereby preventing skin aging phenomena such as fine wrinkles, dullness, and pigmentation, 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. These promoters 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, aging odor, and head odor (including scalp odor), and are therefore suitable for use in external skin compositions such as cosmetics and quasi-drugs that are expected to have such effects.

Claims (6)

An epidermal keratinocyte proliferation promoter, comprising a lactone compound represented by the following formula (I) as an active ingredient:

(In the formula, R is an alkyl group having 2 to 9 carbon atoms.) A skin turnover promoter comprising, as an active ingredient, a lactone compound represented by the following formula (I):

(In the formula, R is an alkyl group having 2 to 9 carbon atoms.) A skin metabolism enhancer comprising a lactone compound represented by the following formula (I) as an active ingredient:

(In the formula, R is an alkyl group having 2 to 9 carbon atoms.) The promoter according to any one of claims 1 to 3, which is used for preventing and/or improving at least one symptom selected from the group consisting of fine wrinkles, loss of skin texture , loss of elasticity, rough skin , and rough skin . The enhancer according to any one of claims 1 to 4, for external use. A skin topical composition 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, loss of skin texture , loss of firmness, stiff skin, and rough skin.

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