JP7365134B2 - Citric acid cycle activator - Google Patents

Description

Application of Article 30, Paragraph 2 of the Patent Act Publication date April 22, 2019 Pola Chemical Industries, Ltd. Home page News release Publication website address http://www. pola-rm. co. jp/news/index. html http://www. pola-rm. co. jp/pdf/release_20190422. pdf Event date: April 24, 2019 Location: Omotesando Hills Space O Posting date: April 24, 2019 POLA Corporation Home page News release Website address: https://www. pola. co. jp/company/news/po20170718/ https://www. pola. co. jp/company/pressrelease/pdf/2019/po20190424. pdf https://www. pola. co. jp/brand/whiteshot/lxmx/ https://www. pola. co. jp/brand/whiteshot/science/#science_f_MV https://www. pola. co. jp/brand/whiteshot/component/

The present invention relates to a component that activates the citric acid cycle and a component that enhances the activation effect.

There is a high demand for beautiful, healthy or youthful skin. In general, the condition of the skin changes significantly due to aging and external stimuli such as ultraviolet rays, and specifically, the appearance of spots and wrinkles increases, and the skin becomes less firm and elastic. In response to these changes in skin condition, various cosmetics and the like have been proposed to improve the condition or suppress the change.
Skin metabolism and turnover are important for improving skin condition, but there are not many cosmetics that target the energy production in skin cells that are involved in these processes.
What has been disclosed so far is to activate cell regeneration and metabolism in the skin by activating sugar uptake in epidermal cells using topical skin preparations containing purine bases such as adenosine monophosphate as active ingredients. There is a method that aims to promote skin whitening and anti-aging effects (Patent Document 1).

By the way, D-pantothenyl alcohol is an alcohol derivative of pantothenic acid, and is a substance that is converted into vitamin B5 (pantothenic acid) in the body. In addition, it has been used as a component of external skin preparations for a long time, and various skin preparations containing D-pantothenyl alcohol have been proposed.
Patent Document 2 describes that a skin cosmetic containing D-pantothenyl alcohol improves skin roughness, especially skin dryness, and improves skin quality.
Patent Document 3 describes that a composition that combines D-pantothenyl alcohol and other whitening ingredients can quickly provide a whitening effect.

Japanese Patent Application Publication No. 2002-370986 Japanese Patent Application Publication No. 2012-41302 International Publication 2015/152384

An object of the present invention is to provide a technique for activating energy circuits in the skin.

As a result of intensive research aimed at solving the above problems, the present inventors discovered that D-pantothenyl alcohol has the effect of activating the citric acid cycle responsible for energy production in cells. Furthermore, the inventors have also discovered that a base containing a specific component can further enhance the citric acid cycle activation effect of D-pantothenyl alcohol on the skin, leading to the completion of the present invention.

That is, the present invention is as follows.
[1] A citric acid cycle activator containing D-pantothenyl alcohol.
[2] A composition for activating the citric acid cycle, containing D-pantothenyl alcohol and a base containing one or more selected from the group consisting of a) to d) below.
a) Phospholipid b) Sterol c) Hyaluronic acid and/or its derivatives and/or their salts d) Polyglycerin fatty acid ester and/or sucrose fatty acid ester
[3] The composition according to [2], wherein the base contains the above a) to d).
[4] The composition according to [2] or [3], which is an external preparation for skin.
[5] The composition according to [4], which is a cosmetic.

The present invention provides a citric acid cycle activator. Furthermore, a base is provided that can further enhance the citric acid cycle activation effect of the agent by delivering and retaining the active ingredient of the agent to the skin epidermis layer. That is, a composition for citric acid cycle activation is provided, which is a combination of the citric acid cycle activator of the present invention and the base.
The citric acid cycle activator and composition of the present invention can activate the citric acid cycle in the skin, so they can promote skin turnover, suppress pigmentation, exhibit a whitening effect, and prevent wrinkles. It can exert anti-aging effects such as improving skin tone and improving firmness and elasticity. It is also expected that the effect will be enhanced by using it in combination with other active ingredients.

Confocal fluorescence micrographs of human epidermal cells stained after culturing in the presence of D-pantothenyl alcohol for 8 hours (green: inactive mitochondria, red: active mitochondria). Confocal fluorescence micrographs of human epidermal cells stained after culturing in the presence of D-pantothenyl alcohol or disodium adenosine monophosphate for 8 hours (green: inactive mitochondria, red: active mitochondria). Confocal fluorescence micrograph of a human three-dimensional cultured epidermal model stained after culturing for 3 hours in the presence of a D-pantothenyl alcohol-containing composition (blue: cell nucleus, red: active mitochondria). Confocal fluorescence micrograph of a human three-dimensional cultured epidermal model stained after culturing for 6 hours in the presence of a D-pantothenyl alcohol-containing composition (blue: cell nucleus, red: active mitochondria).

The citric acid cycle activator of the present invention contains D-pantothenyl alcohol.
D-pantothenyl alcohol is an alcohol type derivative of pantothenic acid and has the structure shown below.
D-pantothenyl alcohol is used as a material for external skin preparations such as cosmetics, and there is no difficulty in obtaining it, and commercially available products can be used as appropriate.

D-pantothenyl alcohol has the effect of activating the citric acid cycle in cells, especially epidermal cells.
Here, "activation of the citric acid cycle" refers to increasing the amount of rotation of the citric acid cycle. Activation of the citric acid cycle can be confirmed by, for example, measuring the products of the citric acid cycle or measuring the mitochondrial activity level using conventional methods.
Furthermore, "activation" refers to the fact that the activity when D-pantothenyl alcohol is added is greater than the activity when it is not added, and is usually 105% or more, preferably 115% or more, and more preferably 120%. The above can be confirmed.

In cells where the citric acid cycle is activated, skin turnover is promoted, which is expected to improve skin conditions such as pigmentation, wrinkles, firmness and elasticity.

The citric acid cycle activator of the present invention can be preferably used in the form of a composition for activating the citric acid cycle, and the composition preferably includes a skin external preparation, and the form of cosmetics and quasi-drugs. is particularly preferred.
The dosage form of the composition according to the present invention includes a lotion type, an emulsifier type such as a milky lotion or a cream, an oil type, an oil gel type, a gel type, a pack, a cleaning agent, a spray type, a sheet mask agent, etc. Can be mentioned.

The content of the citric acid cycle activator in such a composition is preferably 0.01 to 20% by mass, more preferably 0.01 to 20% by mass, based on the total amount of the composition, in terms of D-pantothenyl alcohol. The amount is 1 to 10% by weight, more preferably 0.1 to 5% by weight. Within this range, desired effects can be easily obtained and freedom in prescription design can be ensured.

In order to exert the citric acid cycle activation effect of D-pantothenyl alcohol in desired cells, preferably epidermal cells, it is important to deliver (deliver) D-pantothenyl alcohol to the cells or their vicinity. be. Furthermore, in order to fully exhibit the above action and obtain the effect, it is also important to maintain the presence of D-pantothenyl alcohol in the cell or its vicinity.
Therefore, when using D-pantothenyl alcohol as an embodiment of the composition, it is preferable to combine it with an appropriate base.

That is, as a base for a composition containing D-pantothenyl alcohol, a) phospholipid, b) sterol, c) hyaluronic acid and/or its derivative and/or its salt, and d) polyglycerin fatty acid ester and/or those containing one or more selected from the group consisting of sucrose fatty acid esters are preferred.

a) Phospholipids can form spherules such as liposomes and vesicles in the composition. Therefore, it is possible to carry D-pantothenyl alcohol, and it is possible to deliver D-pantothenyl alcohol to desired cells or their vicinity.
Examples of phospholipids include, but are not limited to, natural phospholipids such as egg yolk lecithin and soybean lecithin, hydrogenated egg yolk lecithin in which unsaturated carbon chains in lecithin are changed to saturated bonds by hydrogenation, phospholipids such as soybean lecithin, Examples include phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, phosphatidylinositol, phosphatidylglycerol, etc. purified from natural lecithin or synthesized. These phospholipids can be used alone or in combination. Hydrogenated lecithin or hydrogenated lecithin with increased concentration of a specific phospholipid may be used.
The content of phospholipids in the composition of the present invention is preferably 0.001 to 10.0% by mass, more preferably 0.005 to 5.0% by mass, and even more preferably It is 0.005 to 3.0% by mass.

b) Since sterols reinforce the membrane structure of small spheres such as liposomes and vesicles, they can stabilize the structure of small spheres holding D-pantothenyl alcohol and maintain it for a long time.
Examples of sterols include animal sterols, plant sterols (phytosterols), fungal sterols, and the like. Examples of animal sterols include cholesterol, cholestanol, and 7-dehydrocholesterol. Furthermore, examples of plant sterols (phytosterols) include sitosterol, stigmasterol, fucosterol, spinasterol, brassicasterol, and the like. Another example is phytostanol, which is a hydrogenated product of plant sterols. Examples of fungal sterols include ergosterol.
The content of sterol in the composition of the present invention is preferably 0.001 to 5.0% by mass, more preferably 0.001 to 2.0% by mass, and even more preferably 0.001 to 5.0% by mass, based on the total amount of the composition. It is .002 to 1.0% by mass.
Furthermore, the mass ratio of phospholipid to sterol content in the composition of the present invention is preferably 1:1 to 20:1, more preferably 4:1 to 10:1. In particular, when hydrogenated lecithin is used as the phospholipid, the ratio is preferably 1:1 to 10:1, more preferably 4:1 to 8:1.

c) Hyaluronic acid and/or its derivatives and/or their salts can promote the penetration of the active ingredients of the composition into the epidermis. This is thought to be because these components tend to form a film on the skin, increasing occlusive properties and increasing the amount of water in the stratum corneum.
Examples of derivatives of hyaluronic acid include, but are not limited to, dimethylsilanol hyaluronate, propylene glycol hyaluronate, acetylated sodium hyaluronate, hydroxypropyltrimonium hyaluronate, hydrolyzed glyceryl hyaluronate, hyaluronic acid crosspolymer, etc. Dimethylsilanol hyaluronate is more preferred.
Examples of salts of hyaluronic acid or its derivatives include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, and metal salts such as aluminum and zinc, but sodium salts are more preferred. preferable.
Hyaluronic acid and/or derivatives thereof and/or salts thereof in the composition of the present invention can be used singly or in combination, and the content thereof is preferably the total amount based on the total amount of the composition. The amount is 0.001 to 5.0% by weight, more preferably 0.001 to 2.0% by weight, and even more preferably 0.002 to 1.0% by weight.

d) Polyglycerol fatty acid ester and/or sucrose fatty acid ester have the effect of making it easier to bind small spheres such as liposomes and vesicles to the basal layer of the epidermis. Therefore, the spherules carrying D-pantothenyl alcohol can be maintained in or near epidermal cells for a long time.
The polyglycerol fatty acid ester is preferably a polyglycerol fatty acid ester in which the fatty acid moiety has 10 to 20 carbon atoms. The fatty acid may be a saturated fatty acid or an unsaturated fatty acid, and may be a straight chain fatty acid or a branched chain fatty acid. Specifically, such fatty acids include capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, arachidic acid, behenic acid, lignoceric acid, lignoceric acid, oleic acid, linoleic acid, and linolenic acid. , arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid. Among these, oleic acid, myristic acid, and lauric acid are preferred.
The average degree of polymerization of glycerin in the polyglycerol fatty acid ester is preferably 3 or more and 15 or less. The lower limit of the glycerin average polymerization degree is preferably 3 or more, more preferably 5 or more, even more preferably 7 or more, and the upper limit is preferably 15 or less, more preferably 13 or less, and even more preferably 10 or less. Although monoesters, diesters, and triesters may be used, monoesters are preferred from the viewpoint of ease of adsorption to the basal layer of the epidermis. More specifically, polyglyceryl-10 monooleate, polyglyceryl-5 oleate, etc. are particularly preferred. Further, polyglycerin with an average degree of polymerization of less than 3 or greater than 15 may be included as long as the effects of the present invention are not impaired.

As the sucrose fatty acid ester, a sucrose fatty acid ester of a fatty acid whose fatty acid moiety has 10 to 20 carbon atoms is preferable. Specifically, such fatty acids include capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, arachidic acid, behenic acid, lignoceric acid, lignoceric acid, oleic acid, linoleic acid, and linolenic acid. , arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid. Among these, oleic acid, myristic acid, and lauric acid are preferred.

Specific examples of the sucrose fatty acid ester in the present invention include sucrose monolaurate, sucrose monomyristate, sucrose monopalmitate, sucrose monostearate, sucrose monoisostearate, and sucrose monoisostearate. Examples include oleic acid esters.
Although monoesters, diesters, and triesters may be used, monoesters are preferred from the viewpoint of ease of adsorption to the basal layer of the epidermis. More specifically, sucrose monoisostearate and sucrose monooleate are particularly preferred.

The polyglycerin fatty acid ester and/or sucrose fatty acid ester in the composition of the present invention can be used in any one kind or in combination of two or more, and the content thereof is preferably 0. 001 to 5.0% by weight, more preferably 0.002 to 2.0% by weight, even more preferably 0.005 to 1.0% by weight.

Since the base according to the present invention can maintain D-pantothenyl alcohol in the basal layer, it can further enhance the citric acid activation effect of D-pantothenyl alcohol in or near epidermal cells.

The base according to the present invention may contain one or more members from the group consisting of a) to d), but from the viewpoint of further exerting the activation effect of the citric acid cycle, it is preferable to contain at least a). and more preferably all of a) to d).

In addition to D-pantothenyl alcohol and the above-mentioned base, the composition of the present invention may optionally contain any components used in ordinary skin preparations as long as they do not impair the effects of the present invention. Such optional ingredients include various active ingredients, oily ingredients, surfactants, polyhydric alcohols, thickeners, powders, ultraviolet absorbers, and the like.

Examples of active ingredients include other whitening ingredients, wrinkle-improving ingredients, anti-inflammatory ingredients, and extracts derived from plants and animals.
Other whitening ingredients are not particularly limited as long as they are commonly used in cosmetics. For example, 4-n-butylresorcinol, ascorbic acid glucoside, 3-O-ethyl ascorbic acid, arbutin, ellagic acid, kojic acid, linoleic acid, nicotinamide, 5,5'-dipropylbiphenyl-2,2'- Examples include diol, disodium 5'-adenylate, potassium 4-methoxysalicylate, and hydroquinone.

The wrinkle-improving ingredient is not particularly limited as long as it is commonly used in cosmetics. For example, isopropyloxopropylaminocarbonylpyrrolidine carbonyl trifluoride, sodium methylpropylaminocarbonylbenzoylaminoacetate, nicotinamide, vitamin A or its derivatives (retinol, retinal, retinoic acid, tretinoin, isotretinoin, tocopherol retinoate, retinol palmitate). , retinol acetate, etc.), benzyl ursolic acid ester, ursolic acid phosphoric ester, betulinic acid benzyl ester, and benzylic acid phosphoric ester.

Anti-inflammatory ingredients include glycyrrhizic acid, glycyrrhetinic acid, allantoin, isopropylmethylphenol, clarinone, glabridin, salicylic acid, tocopherol acetate, tocopherol nicotinate, nicotinic acid amide, pantothenic acid, pantothenyl alcohol, and salts or derivatives thereof. Preferable examples include glycyrrhizic acid and its salts, glycyrrhetinic acid and its salts, pantothenyl alcohol, and pantothenic acid and its salts.

Extracts derived from animals and plants are not particularly limited as long as they are commonly used in cosmetics and the like. For example, akebia extract, asunaro extract, asparagus extract, avocado extract, amacha extract, almond extract, arnica extract, aloe extract, aronia extract, apricot extract, ginkgo biloba extract, indokino extract, fennel extract, oud extract, elegiac extract, eleuthero extract , Scutellaria extract, Scutellaria extract, Scutellaria extract, Orientalis extract, Panax ginseng extract, Hypericum perforatum extract, Dead nettle extract, Orange extract, Perforatum extract, Cucumber extract, Chamomilla extract, Carrot extract, Artemisia mugwort extract, Kiwi extract, Cucumber extract, Guava extract, Kujin extract, gardenia extract, kumazasa extract, clara extract, walnut extract, grapefruit extract, black rice extract, chlorella extract, mulberry extract, keiketou extract, chinensis extract, gentian extract, genus shoko extract, black tea extract, burdock extract, rice extract, rice fermented extract , fermented rice bran extract, rice germ oil, lingonberry extract, salvia extract, soapwort extract, sasa extract, sasanya extract, cypress extract, shiitake extract, rhododendron extract, cypress extract, perilla extract, linden extract, meadow extract, peony extract, ginger extract, Calamus root extract, birch extract, horsetail extract, stevia extract, stevia ferment, hemlock extract, hawthorn extract, elderberry extract, yarrow extract, peppermint extract, sage extract, mallow extract, nebula extract, Japanese cabbage extract, Japanese cabbage extract Extract, rhubarb extract, soybean extract, turmeric extract, thyme extract, dandelion extract, tea extract, clove extract, chimpi extract, sweet tea extract, capsicum extract, ginger extract, calendula extract, tonin extract, spruce extract, dokudami extract, tomato extract, natto extract , Carrot Extract, Garlic Extract, Nova Rose Extract, Hibiscus Extract, Bucchinensis Extract, Lotus Extract, Parsley Extract, Birch Extract, Hamamelis Extract, Hikiokoshi Extract, Cypress Extract, Loquat Extract, Coltsfoot Extract, Coltsfoot Extract, Bucurius Extract, Butcher Bloom Extract, Grape Extract, grape seed extract, loofah extract, safflower extract, peppermint extract, bodega extract, button extract, hop extract, pine extract, mayonara extract, horse chestnut extract, skunk cabbage extract, sapinum extract, melissa extract, mozuku extract, peach extract, cornflower extract, eucalyptus extract , saxifrage extract, yuzu extract, lily extract, lily extract, mugwort extract, lavender extract, green tea extract, apple extract, rooibos tea extract, reishi extract, lettuce extract, lemon extract, forsythia extract, astragalus extract, rose extract, rosemary extract, roma Preferable examples include extracts such as chamomile extract, royal jelly extract, and blackberry extract.

Examples of oily components include polar oils and volatile hydrocarbon oils.
Polar oils include synthetic ester oils such as isopropyl myristate, cetyl octoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyldecyl dimethyloctoate, and lactic acid. Cetyl, myristyl lactate, lanolin acetate, 2-ethylhexyl isononanoate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, ethylene glycol di-2-ethylhexanoate, dipentaerythritol fatty acid ester, N- monoisostearate Alkyl glycol, neopentyl glycol dicaprate, diisostearyl malate, glyceryl di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentane tetra-2-ethylhexanoate Mention may be made of erythritol, glyceryl tri-2-ethylhexanoate, and trimethylolpropane triisostearate.

Furthermore, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, glyceryl trimyristate, tri-2-heptylundecanoic acid glyceride, castor oil fatty acid methyl ester, oleic acid oil, cetostearyl alcohol, acetoglyceride, palmitic acid 2 -Heptylundecyl, diisobutyl adipate, N-lauroyl-L-glutamic acid-2-octyldodecyl ester, di-2-heptylundecyl adipate, ethyl laurate, di-2-ethylhexyl sebacate, 2-hexyl myristate Also included are decyl, 2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebatate, 2-ethylhexyl succinate, ethyl acetate, butyl acetate, amyl acetate, triethyl citrate, octyl methoxycinnamate, and the like.

In addition, natural oils include avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat germ oil, sasanqua oil, castor oil, linseed oil, Safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, Japanese tung oil, jojoba oil, germ oil, triglycerin, glyceryl trioctanoate, glyceryl triisopalmitate etc.

Examples of volatile hydrocarbon oils include isododecane and isohexadecane.

Examples of surfactants include fatty acid soaps (sodium laurate, sodium palmitate, etc.), anionic surfactants such as potassium lauryl sulfate, alkyl sulfate triethanolamine ether, stearyltrimethylammonium chloride, benzalkonium chloride, and laurylamine oxide. cationic surfactants such as, betaine surfactants (alkylbetaine, amidobetaine, sulfobetaine, etc.), imidazoline amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy 2 sodium salts, etc.), amphoteric surfactants such as acylmethyltaurine, sorbitan fatty acid esters (sorbitan monostearate, sorbitan sesquioleate, etc.), propylene glycol fatty acid esters (propylene glycol monostearate, etc.), hydrogenated castor oil Derivatives, glycerin alkyl ethers, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbitan fatty acid esters (POE-sorbitan monolaurate, etc.), POE glycerin fatty acid esters (POE -glycerin monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE 2-octyl dodecyl ether, etc.), POE alkylphenyl ethers (POE nonylphenyl ether, etc.), Pluronic types, POE/POP alkyl ethers (POE/POP2-decyltetradecyl ether, etc.), Tetronics, POE castor oil/hydrogenated castor oil derivatives (POE castor oil, POE hydrogenated castor oil, etc.), sucrose fatty acid esters , nonionic surfactants such as alkyl glucosides, and the like.

Polyhydric alcohols include polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4 -hexylene glycol, 1,2-hexanediol, 1,2-octanediol and the like.

Thickeners include guar gum, quince seed, carrageenan, galactan, gum arabic, pectin, mannan, starch, xanthan gum, curdlan, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, methylhydroxypropylcellulose, chondroitin sulfate, dermatan sulfate, glycogen, Heparan sulfate, hyaluronic acid, sodium hyaluronate, tragacanth gum, keratan sulfate, chondroitin, mucoitin sulfate, hydroxyethyl guar gum, carboxymethyl guar gum, dextran, keratosulfate, locust bean gum, succinoglucan, caronin acid, chitin, chitosan, carboxymethyl Examples include chitin, agar, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, alkyl-modified carboxyvinyl polymer, sodium polyacrylate, polyethylene glycol, bentonite, and the like.

Examples of powders include powders such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, silica anhydride, aluminum oxide, and barium sulfate, which may have their surfaces treated. Inorganic pigments such as red iron oxide, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine blue, navy blue, titanium oxide, and zinc oxide, which may be treated; titanium mica, fish phosphorous foil, which may have a surface treated; Pearling agents such as bismuth oxychloride, which may be laked, Red No. 202, Red No. 228, Red No. 226, Yellow No. 4, Blue No. 404, Yellow No. 5, Red No. 505, Red No. 230, Red No. 223 Organic pigments such as No. 201, Orange No. 201, Red No. 213, Yellow No. 204, Yellow No. 203, Blue No. 1, Green No. 201, Purple No. 201, Red No. 204, polyethylene powder, polymethyl methacrylate, nylon powder, Examples include organic powders such as organopolysiloxane elastomers.

Examples of UV absorbers include para-aminobenzoic acid-based UV absorbers, anthranilic acid-based UV absorbers, salicylic acid-based UV absorbers, cinnamic acid-based UV absorbers, benzophenone-based UV absorbers, sugar-based UV absorbers, and 2-(2 Examples include ultraviolet absorbers such as '-hydroxy-5'-t-octylphenyl)benzotriazole and 4-methoxy-4'-t-butyldibenzoylmethane.

EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to examples, but the present invention is not limited to the following examples unless it exceeds the gist thereof.

<Test Example 1> Examination of the influence of D-pantothenyl alcohol on the citric acid cycle Adult human epidermal cells (Lot. 03021, Kurabo Industries) were seeded at 5 x 10 ⁵ cells/well in a 24-well plate, and HuMedia-KG2 medium was added. (Kurabo) for 24 hours at 37° C. in a 5% CO ₂ environment. After culturing, the medium was replaced with a medium containing 100 μg/mL of D-pantothenyl alcohol (Example 1), a medium containing 0.29 μM disodium adenosine monophosphate (Comparative Example 1), or a medium without any reagent added (control). Note that the concentration of adenosine monophosphate disodium was set at the lowest concentration at which a cell proliferation promoting effect has been confirmed (Furukawa et. Al., Arch. Dermatol. Res., (2008) 300: 485-493). After replacing the medium, the cells were cultured for 8 hours at 37°C in a 5% CO ₂ environment, and 4 μmol/L of staining solution (JC-1 Dye (Dojindo) was added and incubated for 30 minutes for staining. After staining, HBSS was used. The cells were washed twice with an imaging buffer (Dojindo) and observed under a confocal fluorescence microscope (Ex 561 nm/Em 560-610 nm). The results are shown in FIGS. 1 and 2.

Using images of three arbitrary fields of view, an experienced evaluator visually calculates the ratio (%) of the red-stained area to the field of view for each image, and applies the average value of the three fields of view to the following four levels. This was used to evaluate the mitochondrial activity level.
evaluated. The results are shown in Table 1.
◎: Very high activity...25% or more ○: High activity...10% or more and less than 25% △: Low activity...5% or more and less than 10% ×: Almost no activity・Less than 5%

In Example 1, higher levels of mitochondrial activity were observed compared to the control. On the other hand, disodium adenosine monophosphate of Comparative Example 1 has been reported to have an effect of activating cellular sugar uptake (Patent Document 1), but no effect of increasing mitochondrial activity level was observed.

<Test Example 2> Examination of the influence of the combination of D-pantothenyl alcohol and base on the citric acid cycle A human three-dimensional cultured epidermis model (Lab Cyte EPI-MODEL24: J-TECH) was removed from the agarose gel, and assay medium (J -TECH) was transferred to a 24-well plate in which 500 μL was dispensed and cultured for 18 hours at 37° C. in a 5% CO ₂ environment. After culturing, the assay medium was replaced with a new assay medium, and 50 μL/well of each sample shown in Table 2 diluted 10 times was added. Culture was carried out for 3 or 6 hours at 37° C. in a 5% CO ₂ environment. After culturing, the medium was removed by suction using an aspirator, and the epidermal model was washed three times with PBS. The epidermal model was cut out from the well using a scalpel and soaked in the staining solution for 45 minutes. The staining solution used was an assay medium to which JC-1 Dye (Dojindo) was added at a final concentration of 8 μmol/L and Hoechest 33342 (Dojindo) at a final concentration of 1 μg/mL. After staining, the epidermal model was washed twice using HBSS, mounted in a slide glass using imaging buffer (Dojindo), and observed under a confocal fluorescence microscope (Ex561 nm/Em 560-610 nm). The results are shown in Figures 3 and 4.

Mitochondrial activity was evaluated in the same manner as in Test Example 1 using images from three arbitrary fields of view.
evaluated. The results are shown in Table 3.

After adding the sample and culturing for 3 hours, higher mitochondrial activity levels were observed in Examples 3 to 6 compared to Example 2. In particular, higher mitochondrial activity levels were observed in Example 3 compared to Examples 4-6.
After adding the sample and culturing for 6 hours, a decrease in the mitochondrial activity level over time was observed in Example 2, but higher mitochondrial activity levels were observed in Examples 3 to 6 compared to Example 2. In particular, in Example 3, high mitochondrial activity levels were maintained.

The present invention provides a citric acid cycle activator and a base that can further enhance its action. The present invention is industrially useful because it is possible to activate the citric acid cycle in the skin, and thus it is possible to design a composition that can exert a useful effect on the skin.

Claims (3)

A composition for activating the citric acid cycle, comprising D-pantothenyl alcohol and a base containing the following a) to d ) ,
A composition in which the mass ratio of the contents of the following a) and the following b) in the composition is 4:1 to 10:1.
a) phospholipids b) sterols c) hyaluronic acid and/or derivatives thereof and/or salts thereof ,
The derivative is one or more selected from the group consisting of dimethylsilanol hyaluronate, propylene glycol hyaluronate, acetylated sodium hyaluronate, hydroxypropyltrimonium hyaluronate, hydrolyzed glyceryl hyaluronate, and hyaluronic acid crosspolymer.
d) Polyglycerol fatty acid ester and/or sucrose fatty acid ester The composition according to claim 1 , which is an external preparation for skin. The composition according to claim 2 , which is a cosmetic.

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