topical skin preparations

Abstract

To provide novel active components which can be added to skin external agents and are useful for promoting extracellular matrix production and preventing or improving skin thinning.SOLUTION: Provided is a skin external agent containing a pyridine derivative, or a pyridine derivative and at least any one of an ascorbic acid derivative, tranexamic acid or a derivative thereof, hydroquinone or a derivative thereof and kojic acid or a derivative thereof, collagen or a derivative thereof, hyaluronic acid or a derivative thereof, as well as a component derived from plants, animals, or microorganisms.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a pyridine derivative and an external skin preparation containing the pyridine derivative and other active ingredients. [Background technology]

[0002] It has been known that skin aging, dryness, rough skin, age spots, and freckles are caused by a complex interaction of internal factors, such as the inactivation of cell proliferation and differentiation, decreased hormone secretion, and a quantitative decrease in extracellular matrix components, with external factors, such as cell and tissue damage caused by reactive oxygen species induced by sunlight (ultraviolet rays), or inflammation.

[0003] In recent years, there has been a demand for active ingredients that not only suppress damage to the surface of the skin but also inhibit the denaturation or cross-linking of extracellular matrix components present in the dermis layer of the skin, thereby preventing and improving wrinkle formation and loss of skin elasticity.

[0004] Ingredients that protect the skin from ultraviolet rays, dryness, and the like have been proposed in the past (Patent Documents 1 to 3), but no active ingredients have been known whose functions of improving the condition of the epidermis of the skin and suppressing the degeneration of extracellular matrix components present in the dermis have been fully elucidated.

[0005] [Patent Document 1] Japanese Patent Publication No. 51-123836 [Patent Document 2] Japanese Patent Publication No. 05-500230 [Patent Document 3] Japanese Patent Publication No. 09-194383 DISCLOSURE OF THE INVENTION [Problem to be solved by the invention]

[0006] The present invention aims to discover an active ingredient that promotes the production of extracellular matrix, prevents or improves the phenomenon of thinning of the skin caused by ultraviolet rays, aging, decreased hormone secretion, etc., and prevents or improves wrinkles and sagging of the epidermis and dermis. [Means for solving the problem]

[0007] The present invention relates to an agent for preventing or improving skin thinning, which contains as an active ingredient at least one of pyridine-3-carboxylic acid amide, eggplant extract, and Veronica bark extract. [Effects of the Invention]

[0008] According to the present invention, it is possible to provide an external skin preparation that prevents or improves skin thinning and has the effect of preventing or improving wrinkles or sagging. DETAILED DESCRIPTION OF THE INVENTION

[0009] Preferred embodiments of the present invention will now be described in detail. In the present invention, examples of pyridine derivatives include pyridine-3-carboxylic acid, pyridine-3-carboxylic acid amide (also known as niacinamide), isoniazid, and the like.

[0010] In addition, in the present invention, examples of components with which a pyridine derivative is preferably combined include ascorbic acid or a derivative thereof, tranexamic acid or a derivative thereof, hydroquinone or a derivative thereof, kojic acid or a derivative thereof, collagen or a derivative thereof, hyaluronic acid or a derivative thereof, yeast extract or a hydrolysate thereof, and plant- or animal-derived components.

[0011] Examples of ascorbic acid or its derivatives include ascorbic acid ester salts such as sodium ascorbate, calcium ascorbate, sodium L-ascorbic acid 2-phosphate, magnesium L-ascorbic acid 2-phosphate, sodium L-ascorbic acid 2-sulfate, and magnesium L-ascorbic acid 2-sulfate; ascorbic acid sugar derivatives such as L-ascorbic acid 2-glucoside, L-ascorbic acid 5-glucoside, ascorbyl tocopheryl maleate, ascorbyl tocopheryl phosphate K, myristyl 3-glyceryl ascorbate, and caprylyl 2-glyceryl ascorbate; and ascorbic acid sugar derivatives thereof. and the like), L-ascorbic acid tetrafatty acid esters such as L-ascorbic acid tetraisopalmitate and L-ascorbic acid tetralaurate, 3-O-ethyl ascorbic acid, L-ascorbic acid-2-phosphate-6-O-sodium palmitate, glyceryl ascorbic acid or an acylated derivative thereof, ascorbic acid glycerin derivatives such as bisglyceryl ascorbic acid, L-ascorbic acid aminopropyl phosphate, hyaluronic acid derivatives of L-ascorbic acid, 3-OD lactose-L-ascorbic acid, and isostearyl ascorbyl phosphate.

[0012] Examples of the derivatives of tranexamic acid include tranexamic acid esters (for example, tranexamic acid lauryl ester, tranexamic acid hexadecyl ester, tranexamic acid cetyl ester, or salts thereof), and amides of tranexamic acid (for example, tranexamic acid methylamide).

[0013] Examples of hydroquinone derivatives include arbutin (hydroquinone-β-D-glucopyranoside) and α-arbutin (hydroquinone-α-D-glucopyranoside).

[0014] Examples of the derivatives of kojic acid include kojic acid esters such as kojic acid monobutyrate, kojic acid monocaprate, kojic acid monopalmitate, and kojic acid dibutyrate, kojic acid ethers, and kojic acid sugar derivatives such as kojic acid glucoside.

[0015] In the present invention, examples of yeasts that can be used include yeasts of the genus Saccharomyces, such as Saccharomyces cerevisiae, Saccharomyces awamori, Saccharomyces chevalieri, Saccharomyces carlsbergensis, and Saccharomyces bayonus; yeasts of the genus Galactomyces; yeasts of the genus Torulaspora, such as Torulaspora delbruekii, Torulaspora fermentati, and Torulaspora rosei; yeasts of the genus Torulaspora, such as Zygosaccharomyces rouxii and Zygosaccharomyces Yeasts of the genus Zygosaccharomyces, such as Zygosaccharomyces soya, Zygosaccharomyces sake, Zygosaccharomyces miso, and Zygosaccharomyces lactis; yeasts of the genus Candida, such as Candida versatilis, Candida etchellsii, Candida kefyr, Candida sake, and Candida scottii; yeasts of the genus Aureobasidium pullulans, Aureobasidium mansonii, and Aureobasidium Examples of yeasts of the genus Aureobasidium include Aureobasideium microstictum. The yeast according to the present invention may be any of sake yeast, wine yeast, brewer's yeast, yeast derived from plant flowers (rose, plum, cherry, camellia, lily, etc.), and yeast derived from the sea.

[0016] In the present invention, collagen derived from fish is particularly preferred, for example, fish from the Alfonsidae family, such as alfonsino, blue alfonsino, pufferfish, and alfonsino; fish from the Scorpaenidae family, such as scorpionfish and scorpionfish; fish from the Scorpaenidae family, such as red sea bream, crimson sea bream, and yellow sea bream; fish from the Pelecanidae family, such as red sea bream, crimson sea bream, and yellow sea bream; fish from the Pelecanidae family, such as conger eel and conger eel; fish from the Anguillididae family, such as eel; fish from the Conger Eel family, such as Japanese conger eel; fish from the Salmonidae family; and fish from the Sharkidae family. The collagen may be hydrolyzed collagen, atelosylated or succinylated collagen, or crosslinked collagen. Furthermore, jellyfish-derived collagen, or collagen hydrolyzed, atelosylated, or succinylated collagen, or even crosslinked collagen may also be used.

[0017] In addition, plant-derived ingredients include grasses, cruciferous plants, Theaceae plants, Rosaceae plants, Paeoniaceae plants, Rutaceae plants, Amaranthaceae plants, Zosteraea plants, Fabaceae plants, Asteraceae plants, Leguminosae plants, Malvaceae plants, Gentianaceae plants, Lamiaceae plants, Nelumbaceae plants, Cucurbitaceae plants, Araliaceae plants, Solanaceae plants, Bignoniaceae plants, Actinidiaceae plants, Mulberry plants, Iridaceae plants, Campanulaceae plants, Oleaceae plants, Actinidiaceae plants, Rhamnaceae plants, and Mulberry plants. Examples of the extracts include extracts of one or more plants selected from the Orchidaceae family, Anacardiaceae family, Garciniaceae family, Valenciaceae family, Rutaceae family, Myrtaceae family, Liliaceae family, Crassulaceae family, Cupressaceae family, Convolvulaceae family, and Asparagaceae family, or hydrolysates or fermented products thereof. Examples of the seaweed-derived component include extracts of one or more seaweed selected from the Laminaria family, Myrinaceae family, Ulvaceae family, and Funoriaceae family, or hydrolysates or fermented products thereof. In addition, examples of the naturally derived component include extracts of jellyfish or royal jelly, or hydrolysates or fermented products thereof. Extracts of plants selected from one or more of the above, or hydrolysates or fermented products thereof, can also be used.

[0018] The above-mentioned extracts derived from natural products may be extracted by conventional methods, for example, by contacting the extract with an extraction solvent by appropriate means such as immersion using a solvent, countercurrent extraction, etc. Also, supercritical extraction can be used for preparation.

[0019] Examples of extraction solvents include water; lower alcohols such as methanol, ethanol, and propanol; higher alcohols such as oleyl alcohol, stearyl alcohol, and octyldodecanol; polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, and glycerin; esters such as ethyl acetate, butyl acetate, methyl propionate, and 2-ethylhexylglyceride; ketones such as acetone and methyl ethyl ketone; ethers such as ethyl ether and isopropyl ether; and hydrocarbon solvents such as n-hexane, toluene, and chloroform, which may be used alone or in combination. Among these, the use of a single solvent or a mixture of two or more solvents selected from water, lower alcohols, and polyhydric alcohols is preferred because of their wide applicability to cosmetics.

[0020] When a mixed solvent is used, the mixing ratio is preferably in the range of 1:1 to 25:1 by volume (same applies hereinafter) for a mixed solvent of water and ethyl alcohol, 1:1 to 20:1 for a mixed solvent of water and glycerin, or 1:1 to 20:1 for a mixed solvent of water and 1,3-butylene glycol.

[0021] When preparing the extract of the present invention, it is preferable to maintain the pH of the extract in the range of 4 to 8. In this sense, if necessary, the above-mentioned extraction solvent may be blended with an alkalinity adjuster such as sodium hydroxide, sodium carbonate, potassium hydroxide, or arginine, or an acidity adjuster such as hydrochloric acid, acetic acid, or sulfuric acid to adjust the pH to the desired level.

[0022] The extraction conditions such as extraction temperature and time vary depending on the type of solvent used, extraction method, etc., but for example, in the case of the immersion method, the extraction temperature is preferably in the range of 4 to 90°C, and the extraction time is preferably about 0.1 to 1 week.

[0023] Furthermore, the above-mentioned extracts derived from natural products may be subjected to hydrolysis treatment. For example, when hydrolysis treatment is carried out using an enzyme, it is preferable to use one enzyme selected from the group consisting of proteolytic enzymes such as actinase, papain, chymopapain, trypsin, and pepsin; amylolytic enzymes such as glucoamylase, α-amylase, and β-amylase; cellulose-degrading enzymes such as cellulase, hemicellulase, and pectinase; and lipolytic enzymes such as lipase, or a combination of one or more enzymes selected from each of these enzyme groups.

[0024] Examples of microorganisms (yeast, lactic acid bacteria, koji mold, or Bacillus subtilis) or microorganism-derived components used in the fermentation treatment to obtain the above-mentioned fermented products include the following.

[0025] Furthermore, in the present invention, lactic acid bacteria include, for example, lactic acid bacteria of the genus Lactobacillus such as Lactobacillus plantarum, Lactobacillus brevis, Lactobacillus casei, and Lactobacillus delbrueckii; lactic acid bacteria of the genus Carnobacterium such as Carnobacterium divergens and Carnobacterium piscicola; Leuconostoc mesenteroides, Leuconostoc lactis, and Leuconostoc citreum. Lactic acid bacteria of the genus Leuconostoc such as Streptococcus citreum; lactic acid bacteria of the genus Streptococcus such as Streptococcus faecalis and Streptococcus pyogenes; lactic acid bacteria of the genus Enterococcus such as Enterococcus caseliflavus and Enterococcus sulfreus; lactic acid bacteria of the genus Lactococcus such as Lactococcus plantarum, Lactococcus lactis, and Lactococcus rafinolactis; lactic acid bacteria of the genus Weissella confusa and Weissella candida. Lactic acid bacteria of the genus Veisella, such as Atopobium kandleri; lactic acid bacteria of the genus Atopobium, such as Atopobium minutum and Atopobium parvulus;Examples of lactic acid bacteria include Vagococcus genus lactic acid bacteria such as Vagococcus fluvialis and Vagococcus salmoninarum; and Pediococcus genus lactic acid bacteria such as Pediococcus damnosus and Pediococcus pentosaceus.

[0026] In the present invention, examples of koji mold include yellow koji molds such as Aspergillus oryzae, Aspergillus flavus, Aspergillus polyoxogenes, and Aspergillus sojae; black koji molds such as Aspergillus awamori, Aspergillus kawauchii, Aspergillus usami, and Aspergillus niger; and red koji molds such as Monascus anka and Monascus pilosus.

[0027] In the present invention, examples of Bacillus subtilis include Bacillus natto, Bacillus subtilis, and Bacillus circulans.

[0028] When the above-mentioned suspension or extract is fermented with microorganisms, it is necessary to sterilize the material before the fermentation step to remove any unwanted bacteria that may hinder fermentation. This method of sterilizing and removing unwanted bacteria may involve washing the material for fermentation with sterilizing ethanol or the like beforehand and then suspending it in a sterile solvent such as sterile water. Alternatively, the material for fermentation may be suspended in a solvent and then sterilized by heat sterilization or the like. Commonly used heat sterilization methods include autoclave sterilization, in which the suspension is heated to 120-130°C for 10-20 minutes, and intermittent sterilization, in which the suspension is kept at 80-90°C for 60-120 minutes, repeated once a day for 2-3 days.

[0029] During the fermentation treatment, sugars such as glucose, galactose, fructose, sucrose, maltose, and lactose may be added as a carbon source.

[0030] The sterilized suspension and culture medium are placed in a fermentation tank, and the microorganisms are inoculated and fermented. The inoculation amount of the microorganisms is 10 7 ~10 8 If the inoculum amount is greater than the above range, the fermentation time will not change significantly, while if it is less than the above range, it will take a long time to complete the fermentation, which is not desirable.

[0031] The fermentation temperature is generally in the range of 5 to 50°C, preferably in the range of the optimum temperature for growth of each microorganism. The fermentation period is generally 1 to 10 days, preferably 2 to 5 days, at the optimum temperature. If the fermentation period is shorter than the above-mentioned general range, the fermentation does not proceed sufficiently and the effectiveness of the fermented product tends to decrease. On the other hand, if the fermentation period is longer than 10 days, not only will no further increase in effectiveness be observed, but coloring and an increased fermentation odor will occur, both of which are undesirable.

[0032] When the composition of the present invention is incorporated into an external skin preparation, in addition to the above-mentioned composition of essential ingredients, ingredients commonly used in cosmetics, such as oily ingredients, surfactants (synthetic or natural), moisturizers, anti-inflammatory agents, thickeners, preservatives / bactericides, anti-acne agents, cell activators, powder ingredients, ultraviolet absorbers, antioxidants, whitening agents, anti-wrinkle agents, pigments, fragrances, etc., can be appropriately incorporated as needed.

[0033] Examples of oily components include olive oil, jojoba oil, castor oil, soybean oil, rice oil, rice germ oil, coconut oil, palm oil, cacao oil, meadowfoam oil, shea butter, tea tree oil, avocado oil, macadamia nut oil, bergamot oil, lavender oil, rose oil, bergamot oil, chamomile oil, and other plant-derived oils and fats such as squalane; vitamin A oil; animal-derived oils and fats such as mink oil and turtle oil; waxes such as beeswax, carnauba wax, rice wax, and lanolin; liquid paraffin, petrolatum, and paraffin wax. Examples of suitable glycerides include hydrocarbons such as cocos and squalane; fatty acids such as myristic acid, palmitic acid, stearic acid, oleic acid, isostearic acid, and cis-11-eicosenoic acid; higher alcohols such as lauryl alcohol, cetanol, pantothenyl alcohol, and stearyl alcohol; and synthetic esters and synthetic triglycerides such as isopropyl myristate, isopropyl palmitate, butyl oleate, 2-ethylhexyl glyceride, and higher fatty acid octyldodecyl (e.g., octyldodecyl stearate).

[0034] Examples of surfactants include nonionic surfactants such as polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters, polyoxyethylene sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyoxyethylene hydrogenated castor oil, and polyoxyethylene sorbitol fatty acid esters; fatty acid salts, alkyl sulfates, alkylbenzene sulfonates, polyoxyethylene alkyl ether sulfates, polyoxyethylene fatty amine sulfates, polyoxyethylene alkylphenyl ether sulfates, polyoxyethylene alkyl ether phosphates, α-sulfonated fatty acid alkyl ester salts, polyoxyethylene Examples of surfactants that can be used include anionic surfactants such as phenyl alkyl phenyl ether phosphates; cationic surfactants such as quaternary ammonium salts, primary to tertiary fatty amine salts, trialkylbenzylammonium salts, alkylpyridinium salts, 2-alkyl-1-alkyl-1-hydroxyethylimidazolinium salts, N,N-dialkylmorpholinium salts, and polyethylene polyamine fatty acid amide salts; and amphoteric surfactants such as N,N-dimethyl-N-alkyl-N-carboxymethylammoniobetaine, N,N,N-trialkyl-N-alkyleneammoniocarboxybetaine, N-acylamidopropyl-N', N'-dimethyl-N'-β-hydroxypropylammoniosulfobetaine.

[0035] Examples of emulsifiers and / or emulsifying aids that can be blended include stevia derivatives such as enzyme-treated stevia, saponin or derivatives thereof, casein or its salts (sodium, etc.), sugar and protein complexes, sucrose or esters thereof, lactose, soybean-derived water-soluble polysaccharides, soybean-derived protein and polysaccharide complexes, lanolin or derivatives thereof, cholesterol, stevia derivatives (enzyme-treated stevia, etc.), silicates (aluminum, magnesium, etc.), carbonates (calcium, sodium, etc.), saponin and derivatives thereof, lecithin and derivatives thereof (hydrogenated lecithin, etc.), lactic acid bacteria-fermented rice, lactic acid bacteria-fermented germinated rice, lactic acid bacteria-fermented grains (wheat, beans, millet, etc.), etc.

[0036] Examples of moisturizing agents include glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, polyethylene glycol, sorbitol, xylitol, sodium pyrrolidone carboxylate, and the like, as well as sugars such as trehalose and raffinose, mucopolysaccharides (e.g., hyaluronic acid and its derivatives, hyaluronic acid fermentation liquid, chondroitin and its derivatives, heparin and its derivatives, etc.), elastin and its derivatives, collagen and its derivatives, collagen peptides, NMF-related substances, lactic acid, urea, higher fatty acid octyldodecyl, seaweed extract, estradiol, various amino acids and their derivatives.

[0037] Examples of thickeners include components derived from brown algae, green algae, or red algae, such as alginic acid, agar, carrageenan, and fucoidan; polysaccharides such as pectin and aloe polysaccharide; gums such as tragacanth gum, locust bean gum, xanthan gum, and guar gum; cellulose derivatives such as carboxymethyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose; synthetic polymers such as carboxyvinyl polymers, alkyl-modified carboxyvinyl polymers, polyvinyl alcohol, polyvinylpyrrolidone, and acrylic acid-methacrylic acid copolymers; hyaluronic acid and its derivatives; polyglutamic acid and its derivatives, and polyacrylic acid.

[0038] Anti-inflammatory agents include allantoin, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, β-glycyrrhetinic acid, stearyl glycyrrhetinate, ε-aminocaproic acid, d-camphor, dl-camphor, zinc oxide, panthenol, pyridoxine hydrochloride, and riboflavin or a derivative thereof.

[0039] Examples of antiseptics and disinfectants include urea; benzoic acid or its salts, parahydroxybenzoic acid esters such as methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, and butyl parahydroxybenzoate; phenoxyethanol, dichlorophene, hexachlorophene, chlorhexidine hydrochloride, benzalkonium chloride, salicylic acid, sodium salicylate, zinc pyrithione, benzalkonium chloride, ethanol, undecylenic acid, phenols, and alkane bromide. Examples include chrysoquinolinium, resorcinol, jamal (imidazolidinyl urea), isopropyl methylphenol, triclosan, trichlorocarbanide, trichlorohydroxydiphenol ether, hinokitiol, 1,2-pentanediol, propanediol, concentrated benzalkonium chloride solution 50, essential oils such as peppermint oil and eucalyptus oil, bark distillate, radish fermented liquid, ethanol derived from plants such as sugar cane and corn, or 1,3-butylene glycol.

[0040] Examples of cell activators include pantothenyl alcohol, menthol, dl-menthol, and γ-oryzanol.

[0041] Anti-acne agents include sulfur, salicylic acid or its salts, photosensitizer No. 201, pyridoxine dicaprylate, and the like.

[0042] Examples of powder components include sericite, titanium oxide, talc, kaolin, bentonite, zinc oxide, magnesium carbonate, magnesium oxide, zirconium oxide, barium sulfate, silicic anhydride, mica, nylon powder, polyethylene powder, silk powder, cellulose-based powder, powder of grains (rice, wheat, corn, millet, etc.), powder of beans (soybean, adzuki bean, etc.), etc.

[0043] Examples of ultraviolet absorbers include ethyl paraaminobenzoate, ethylhexyl paradimethylaminobenzoate, amyl salicylate and its derivatives, 2-ethylhexyl paramethoxycinnamate, octyl cinnamate, oxybenzone, 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-tert-butyl-4-methoxybenzoylmethane, 2-(2-hydroxy-5-methylphenyl)benzotriazole, urocanic acid, ethyl urocanate, and aloe extract.

[0044] Examples of antioxidants include butylhydroxyanisole, butylhydroxytoluene, propyl gallate, carotenoids such as astaxanthin, vitamin E and its derivatives (e.g., tocopherol acetate, tocopherol nicotinate), vitamin A and its derivatives (retinol palmitate, etc.), and the like.

[0045] Further, examples of whitening agents include one or more selected from ellagic acid and its derivatives, resorcinol derivatives, 4-methoxysalicylic acid potassium salt, magnolignan (5,5'-dipropyl-biphenyl-2,2'-diol), hydroxybenzoic acid and its derivatives, vitamin E and its derivatives, α-hydroxy acid, and AMP (adenosine monophosphate, adenosine monophosphate).

[0046] Examples of resorcinol derivatives include 4-n-butylresorcinol and 4-isoamylresorcinol; examples of 2,5-dihydroxybenzoic acid derivatives include 2,5-diacetoxybenzoic acid, 2-acetoxy-5-hydroxybenzoic acid, and 2-hydroxy-5-propionyloxybenzoic acid; and examples of α-hydroxy acids include lactic acid, malic acid, succinic acid, citric acid, and α-hydroxyoctanoic acid.

[0047] The present invention will now be described in more detail with reference to Production Examples, Formulation Examples, and Test Examples, but the present invention is not limited thereto. In the following, all parts mean parts by weight, and all % mean % by weight.

[0048] Example 1. Evaluation of fibroblast activation effect Human dermal fibroblasts NB1RGB were cultured in a 96-well microplate containing 0.5% NCS-containing Eagle's minimum essential medium at a concentration of 1 × 10 4 Cells were seeded per well and pre-cultured at 37°C in 5.0% CO for 1 day. A pyridine derivative (pyridine-3-carboxylic acid amide, hereafter referred to as Compound 1) was added to the sample solution at a final concentration of 1 mM. After the addition of the sample solution, the cells were cultured for an additional 3 days under the same conditions as for the pre-culture. The medium was then removed, 0.03% MTT was added, and the cells were incubated at 37°C for 1 hour. The resulting formazan was extracted with isopropanol, and the MTT values ​​were measured at wavelengths of 570-630 nm using a microplate reader (Model 680, Bio-Rad). The same procedure was performed on a control (control) in which medium was added instead of the sample solution. The relative MTT values ​​obtained with each sample addition were calculated and used as the fibroblast MTT activity (%). To confirm the normal function of the test system, a similar test was also performed using a positive control (100 mM glucose) in place of the sample solution.

[0049] The results of Test Example 1 are shown in Table 1 below. [Table 1] JPEG0007788774000001.jpg52124

[0050] As shown in Table 1, it was confirmed that Compound 1 exerts a fibroblast-activating effect. Furthermore, glucose, the positive control, also showed a similar effect, confirming that this experimental system was performed normally.

[0051] Test Example 2: Evaluation of collagen synthesis promotion effect Human dermal fibroblasts NB1RGB were cultured in a 96-well microplate containing 0.5% NCS-containing Eagle's minimum essential medium at a concentration of 1 × 10 4Cells were seeded at 1000 cells / well and pre-cultured at 37°C in 5.0% CO2 for 1 day. A pre-prepared sample solution (Compound 1) was then added to the medium containing the pre-cultured cells at a final concentration of 1 mM to establish a test group. After the addition of the sample solution, the cells were cultured for an additional 5 days under the same conditions as the pre-culture. The medium was then removed, and the cells were fixed with cold methanol and cold ethanol and stained with a saturated aqueous solution of picric acid containing 0.1% Sirius Red. After washing with purified water, the cells were extracted with a 1:1 solution of 0.1% NaOH:methanol. The collagen content was measured at a wavelength of 540 nm using a microplate reader (Model 680, Bio-Rad). The same procedure was repeated for a control (control) in which medium was added instead of the sample solution. The relative collagen content of each sample was calculated relative to the collagen content obtained in the control, and this was used as the collagen synthesis rate (%). In addition, to confirm whether the test system was functioning normally, a similar test was performed with the addition of 1 mM ascorbic acid phosphate magnesium salt (APM) as a positive control instead of the sample solution.

[0052] The results of Test Example 2 are shown in Table 2 below. [Table 2] JPEG0007788774000002.jpg52125

[0053] As shown in Table 2, it was confirmed that Compound 1 exhibits the effect of promoting collagen synthesis in fibroblasts. Furthermore, the positive control APM also showed the same effect, confirming that this experimental system was performed normally.

[0054] Test Example 3. Evaluation of filaggrin gene expression and involucrin gene expression Normal human epidermal cells were cultured at 6 × 10 in HuMedia KG2 medium (Kurabo) containing growth additives. 5The cells were adjusted to a concentration of 1000 cells / mL, and 1 mL of each was seeded into a 6 cm Petri dish and cultured at 37°C under 5% CO2 and saturated steam. After 24 hours of culture, Compound 1 was added to the medium to a final concentration of 1 mM, and the culture was continued. The same procedure was also performed for a control sample (no sample added). After 24 hours of culture, cells from each test group were recovered with 1 mL of Trizol reagent (Invitrogen). 200 μL of chloroform (Wako Pure Chemical Industries, Ltd.) was added to the recovered cells, mixed by stirring, and centrifuged at 15,000 rpm and 4°C for 15 minutes in a centrifuge (TOMY MX-160). 400 μL of the aqueous layer was then removed. 500 μL of isopropanol (Wako Pure Chemical Industries, Ltd.) was added to the recovered aqueous layer, mixed by stirring, and centrifuged at 15,000 rpm and 4°C for 15 minutes to obtain a total RNA precipitate. The total RNA was washed by adding 1 mL of 75% ethanol and vortexing. The mixture was then centrifuged at 15,000 rpm at 4°C for 15 minutes to recover the precipitate. The recovered total RNA was reverse-transcribed using a designated kit (PrimeScript RT reagent Kit with gDNA Eraser (Perfect Real Time) [manufactured by Takara Bio Inc.]) to synthesize cDNA. Using the synthesized cDNA as a sample, expression of the filaggrin gene, involucrin gene, and the internal standard β-actin gene were detected using the Thermal Cycler Dice® Real Time System Single [manufactured by Takara Bio Inc.] and SYBR® Premix Ex Taq™ II (Perfect Real Time) [manufactured by Takara Bio Inc.]. β-actin is a housekeeping gene (a gene expressed at a constant level in many tissues and cells, which is constantly expressed and essential for cell maintenance and proliferation). Because its expression level is always constant, it is used as an internal standard in PCR experiments. The test results were obtained by comparing the expression levels of the filaggrin gene and the involucrin gene in each test group, with the expression level of the β-actin gene held constant.In this test system, the expression level of each gene in the test group was determined as a relative value when the expression level of the gene in the control group was set to 100.

[0055] The results of Test Example 3 are shown in Table 3. [Table 3] JPEG0007788774000003.jpg50159

[0056] As shown in Table 3, it was confirmed that Compound 1 has the effect of enhancing the expression of the filaggrin gene and the involucrin gene. This enhancement of gene expression suggests an effect of enhancing the barrier function in the epidermis.

[0057] To evaluate skin thinning, we focused on the hypoxia-inducible factor HIF-1α (Biochemistry, Vol. 85, No. 3, pp. 187-195, 2013), which is involved in homeostatic mechanisms such as maintaining stem cells and controlling inflammation, and measured the effect of the active ingredient of the present invention in promoting the transcriptional activity of HIF-1α.

[0058] Test Example 4. Evaluation of transcriptional activity of HIF-1α Normal human epidermal cells were grown in Humedia-KG2 (Kurabo) containing a growth additive at 1 × 10 5The cells were prepared at a concentration of 100 μL / mL, and 100 μL was seeded into a 96-well microplate. The cells were cultured at 37°C under 5% CO2 and saturated steam. After 24 hours of culture, a firefly luciferase reporter vector containing a HIF-1α binding sequence (HRE) and a vector containing Renilla luciferase as an internal standard (Cignal HIF Pathway Reporter Assay Kit) [QIAGEN] were transfected into the cells using ViaFect transfection reagent (Promega). After 24 hours, a sample solution was added to the medium. Compound 1 was used as the sample solution, and the sample solution was added to the medium to a final concentration of 1 mM or 2 mM. After 24 hours, the cell contents were extracted, and the luciferase activity of the cell extract was measured using a luciferase assay system (Promega) and a luminometer (Promega GloMax-Multi+Detection System). The HIF-1α transcription activity per cell was calculated by dividing the firefly luciferase measurement value (HRE transcription amount) by the Renilla luciferase measurement value (cell amount).The HIF-1α transcription activity in the control group, in which culture medium was added instead of the sample solution as a control, was set at 100, and the relative value was calculated.

[0059] The results of Test Example 4 are shown in Table 4. [Table 4] JPEG0007788774000004.jpg52125

[0060] As shown in Table 4, Compound 1 was confirmed to have the effect of enhancing HIF-1α transcription activity. This enhancement of gene expression is suggested to improve the age-related decline in HIF-1α transcription activity and maintain stem cell functionality, thereby improving epidermal condition and thinning.

[0061] Test example 3. Monitor test (1) Sample preparation Control lotion and Sample 1 lotion shown in Table 5 were prepared. [Table 5] JPEG0007788774000005.jpg71128 (2) Test method Before the start of the test, replicas were taken of wrinkles at the corners of the eyes. The subjects were asked to apply an appropriate amount of the control lotion to the corner of their right eye and sample 1 lotion lotion B to the corner of their left eye twice daily, morning and evening. The test was conducted blind, with the subjects not informed of the contents of the lotions. The condition of the wrinkles after four months was assessed by taking replicas. After the test was completed, the wrinkle area ratio and wrinkle volume ratio were analyzed using oblique light analysis on the replicas taken. (3) Test results The test results are shown in Table 6. [Table 6] JPEG0007788774000006.jpg50117

[0062] As shown in Table 6, it was confirmed that Compound 1 exhibits an effect of improving wrinkles.

[0063] The pyridine derivative may further be selected from the group consisting of ascorbic acid derivatives, tranexamic acid or derivatives thereof, hydroquinone or derivatives thereof, kojic acid or derivatives thereof, collagen or hydrolysates thereof, yeast extracts or hydrolysates, lactic acid bacteria cultures, grasses, cruciferous plants, Theaceae plants, Rosaceae plants, Paeoniae plants, Rutaceae plants, Amaranthaceae plants, Zosteraea plants, Fabaceae plants, Asteraceae plants, Fabaceae plants, Malvaceae plants, Gentianaceae plants, Lamiaceae plants, Nelumbaceae plants, Cucurbitaceae plants, Araliaceae plants, Solanaceae plants, Bignoniaceae plants, Actinidiaceae plants, Mulberry plants, Iridaceae plants, Campanulaceae plants, Oleaceae plants, Actinidiaceae plants, and Mulberry plants. and extracts of one or more plants selected from the family Rhamnaceae, Orchidaceae, Anacardiaceae, Garciniaceae, Valenciaceae, Rutaceae, Myrtaceae, Liliaceae, Crassulaceae, Cupressaceae, Convolvulaceae, and Asparagaceae, or hydrolysates or fermented products thereof; extracts of one or more seaweed selected from the family Laminaria, Mirrataceae, and Ulvulaceae, or hydrolysates or fermented products thereof; jellyfish (autolyzed products of moon jellyfish, Nomura's jellyfish, etc.); hydrolysates or fermented products of hyaluronic acid; and extracts of royal jelly, or hydrolysates or fermented products thereof.

[0064] As ingredients derived from grass plants, particularly preferred are rice leaf hydrolysate, rice extract hydrolysate, rice bran extract hydrolysate, germinated brown rice hydrolysate, rice fermentation liquid, sake lees extract derived from sake, bamboo shoot skin extract from Madake or Moso bamboo, and fermented Job's tears seed. Furthermore, as Brassicaceae plants, particularly preferred are seed extracts or hydrolysates or fermented products of Hakugai, Ogai, or Kokugai. Furthermore, as ingredients derived from Theaceae plants, particularly preferred are green tea (Yabukita, Samidori, Asahi, Goko, Ujimidori, Kyomidori, Ujihikari, Samidori, Benifuuki, etc.) and black tea (Darjeeling, Assam, Ceylon, Earl Grey, Honey Black Tea, etc.). As ingredients derived from Rosaceae plants, particularly preferred are Damask rose flower extract, peach flower, leaf, or immature fruit extract, apricot fruit or seed extract, strawberry flower extract, and cherry blossom flower or leaf extract. Furthermore, as components derived from Paeoniaceae plants, extracts of peony root or flower and peony flower or root are preferred. As components derived from Amaranthaceae plants, Salicornia extract is particularly preferred. As components derived from Zosteraea plants, extracts of Zostera marina or Zostera kohlrabi are particularly preferred. As components derived from Leguminosae plants, extracts of white soybean or black soybean or their hydrolysates, fermented soy milk, adzuki bean extract, red clover extract, and pueraria lobata root extract are particularly preferred. As components derived from Asteraceae plants, burdock root extract, sunflower sprout extract, Arctium gracilis extract, arnica extract, and chamomile flower extract are particularly preferred. As components derived from Malvaceae plants, fermented products of hibiscus, rose of sharon, or hibiscus are preferred. As components derived from Gentianaceae plants, gentian extract is preferred. As components derived from Lamiaceae plants, perilla extract and barberry fruit extract are preferred. As a component derived from a plant of the Nelumbo family, particularly preferred is a lotus flower or lotus seed extract or a fermented lotus seed product. As a component derived from a plant of the Cucurbitaceae family, particularly preferred is a loofah extract. As a component derived from a plant of the Araliaceae family, a ginseng extract or fermented product is preferred. As a component derived from a plant of the Solanaceae family, an extract of eggplant (long eggplant, water eggplant, rice eggplant, Kamo eggplant, etc.) is included. As a component derived from a plant of the Bignoniaceae family, a Pau d'Arco bark extract is preferred. As a component derived from a plant of the Actinidiaceae family, an immature kiwi extract is preferred.As components derived from plants of the Moraceae family, mulberry bark extract, mulberry fruit extract, and fig fruit or bark extract are preferred. As components derived from plants of the Rhamnaceae family, jujube fruit extract is preferred. Furthermore, as components derived from plants of the Iridaceae family, saffron is preferred. As components derived from plants of the Campanulaceae family, an extract or hydrolysate of Codonopsis gracilis root is preferred. As components derived from plants of the Anacardiaceae family, mango fruit extract is particularly preferred. As components derived from plants of the Garciniaceae family, mangosteen fruit extract is particularly preferred. Furthermore, as components derived from plants of the Valenciaceae family, cherimoya fruit extract is preferred. As components derived from plants of the Rutaceae family, extracts of mandarin orange, bergamot fruit, grapefruit or banpeiyu fruit (including immature fruits), or Japanese pepper seed extract are preferred. As components derived from plants of the Liliaceae family, extracts of daylilies, daylilies, Casablanca lilies, Madonna lilies, or Japanese lilies are preferred. As a component derived from a Crassulaceae plant, an extract or fermented product of Rhodiola rosea (Rhodiola quinata) is particularly preferred. As a component derived from a plant of the Oleaceae family, an extract of jasmine flower is particularly preferred. As a plant of the Cupressaceae family, an extract of Juniperus communis fruit is particularly preferred. As a component derived from a plant of the Myrtaceae family, an extract of guava leaf is particularly preferred. As a plant of the Orchidaceae family, an extract of Bletilla sieboldii root (white orchid) is particularly preferred. As a component derived from a plant of the Convolvulaceae family, an extract of sweet potato or its fermented product, or an extract of sweet potato shochu lees or its fermented product is particularly preferred. Furthermore, as a plant of the Asparagaceae family, asparagus (green asparagus and white asparagus) is particularly preferred. As a component derived from seaweed of the Laminaceae family, a kelp extract is particularly preferred, as a component derived from seaweed of the Mirinaceae family, an extract of Katamen-kirinsai is particularly preferred, and as a component derived from seaweed of the Ulva family, an extract of Ulva pertusa is particularly preferred. As a component derived from seaweed of the Funoriaceae family, an extract of Funori is particularly preferred.

[0065] Test Example 7: Evaluation test of fibroblast activation effect The synergistic effect of fibroblast activation on a combination composition of Compound 1 and any one of yeast hydrolysate (ingredient 1), rice bran extract hydrolysate (ingredient 2), Job's tears seed fermentation product (ingredient 3), Salicornia extract (ingredient 4), Zostera marina extract (ingredient 5), chamomile extract (ingredient 6), sunflower sprout extract (ingredient 7), hibiscus flower fermentation product (ingredient 8), perilla leaf extract (ingredient 9), Veronica japonica fruit extract (ingredient 10), gentian extract (ingredient 11), lotus seed fermentation product (ingredient 12), loofah extract (ingredient 13), jujube fruit extract (ingredient 14), Codonopsis radix root (ingredient 15), Daylily bud fermentation product (ingredient 16), Bletilla striata root extract (ingredient 17), and Laminaria japonica root extract (ingredient 18) was confirmed using the same method as in Test Example 1.

[0066] For example, component 1 can be produced by the following method. Specifically, yeast (Saccharomyces cerevisiae) was added to 100 mL of GP medium containing 1.0% glucose and 0.5% peptone, which had been pre-sterilized under high pressure, and then cultured at 30°C under aeration and agitation to obtain a pre-culture solution. This pre-culture solution was then added to 900 mL of the same GP medium, which had been separately prepared and pre-sterilized under high pressure, and cultured at 30°C under aeration and agitation to obtain a yeast slurry. Purified water and 1N hydrochloric acid solution were added to this yeast slurry, and the mixture was subjected to acid hydrolysis at 90°C for 2 hours with agitation. The solution was then filtered, and the pH was adjusted to 5.5 with 1N sodium hydroxide solution to obtain a yeast hydrolysate.

[0067] For example, component 2 is described in JP-A No. 2000-264834, component 3 is described in JP-A No. 2010-138139, component 4 is described in JP-A No. 2005-145878, component 5 is described in JP-A No. 2012-077035, component 7 is described in JP-A No. 2016-000706, component 8 is described in JP-A No. 2006-347925, component 9 is described in JP-A No. 2014-169253, component 10 is described in JP-A No. 2011-225503, and component 11 is described in JP-A No. 2012-077035. Component 11 can be prepared based on the description in JP 2005-298489 A, component 12 can be prepared based on the description in JP 2005-222622 A, component 13 can be prepared based on the description in JP 2016-222622 A, component 14 can be prepared based on the description in JP 2019-119713 A, component 15 can be prepared based on the description in JP 2018-193335 A, component 16 can be prepared based on the description in JP 2018-193336 A, component 17 can be prepared based on the description in JP 2004-262894 A, and component 18 can be prepared based on the description in JP 2005-314230 A.

[0068] Component 6 can be prepared according to the following manufacturing example: First, 1000 g of purified water was added to 100 g of dried chamomile flowers, and the mixture was extracted at 4°C for 48 hours. This was then filtered to obtain 870 g of a brown, transparent chamomile extract (solid concentration: 1.02%).

[0069] In Test Example 2, the sample solution (one of components 1 to 18) was prepared by adding each component to the medium so that the final concentration of each component as a solution relative to the total volume of the medium was 1.0% or 2.0%.

[0070] The results of Test Example 7 are shown in Tables 7a to 7d. [Table 7a] JPEG0007788774000007.jpg131134[Table 7b] JPEG0007788774000008.jpg132135 [Table 7c] JPEG0007788774000009.jpg132139[Table 7d] JPEG0007788774000010.jpg88135

[0071] As shown in Tables 7a to 7d, it was confirmed that Compound 1 exhibits a synergistic effect in fibroblast activation when used in combination with any one of Components 1 to 18. Thus, Compound 1, when used in combination with any one of Components 1 to 18, is expected to activate dermal cells, promote the synthesis of ECM components, and produce a synergistic effect of improving wrinkles, sagging, and the like.

[0072] Test Example 8: Evaluation of synergistic effect in promoting collagen synthesis The synergistic effect of promoting collagen synthesis was confirmed for a combination composition of compound 1 with any one of eelgrass extract (ingredient 19), rice extract hydrolysate (ingredient 20), royal jelly fermentation product (ingredient 21), rice leaf hydrolysate (ingredient 22), bamboo shoot skin extract (ingredient 23), black soybean hydrolysate (ingredient 24), black soybean fermentation liquid (ingredient 25), white soybean fermentation product (ingredient 26), ginseng extract (ingredient 27), and eggplant extract (ingredient 28) using the same method as in Test Example 2. The collagen synthesis promoting effect of ascorbic acid 2-glucoside, which is preferably used in combination with compound 1, was also confirmed. Here, for example, component 19 can be prepared based on the description in JP-A No. 2012-077035, component 20 based on the description in JP-A No. 04-029776, component 21 based on the description in JP-A No. 2006-143676, component 22 based on the description in JP-A No. 2013-103906, component 23 based on the description in JP-A No. 2015-113291, component 24 based on the description in JP-A No. 2019-014669, component 26 based on the description in JP-A No. 2016-222622, and component 28 based on the description in JP-A No. 2008-69074.

[0073] Component 25 can be prepared by the following manufacturing example. 400 g of purified water was added to 50 g of crushed black soybean seeds, and the mixture was sterilized by heating. 100 ml of lactic acid bacteria (Lactobacillus delbrueckii) was added to the suspension. 8 The cells were inoculated at 1000 / mL and cultured statically for 3 days at 30° C. under a nitrogen atmosphere. After the culture was completed, the culture was sterilized by heating and filtered to obtain 707 g of a solution of soybean seeds fermented by lactic acid bacteria (solid concentration 6.08%).

[0074] Component 27 can be prepared by the following production example. 400 g of purified water and 170 g of 1,3-butylene glycol were added to 100 g of dried ginseng, and the mixture was stirred at 40° C. for 24 hours. This was filtered to obtain 500 g of a brown, transparent carrot extract solution (solid concentration: 3.54%).

[0075] In Test Example 2, the sample solution (any one of components 19 to 28) was prepared by adding each component to the medium so that the final concentration of each component as a solution relative to the total volume of the medium was 1.0% or 2.0%.

[0076] The results of the above tests are shown in Table 8. [Table 8a] JPEG0007788774000011.jpg117101[Table 8b] JPEG0007788774000012.jpg93101

[0077] As shown in Tables 8a and 8b, it was confirmed that compound 1 exerted a synergistic effect in promoting collagen synthesis when used in combination with any of ingredients 19 to 28.

[0078] Test Example 9: Evaluation of the effect of promoting MCSP expression The effect of compound 1 on promoting MCSP expression was evaluated using MCSP (Melanoma-associated chondroitin sulfate proteoglycan), a marker protein for epidermal stem cells. Furthermore, the effect of any one of the following components on promoting MCSP expression was evaluated: Barkberry fruit extract (component 10), jujube fruit extract (component 14), and eggplant extract (component 28).

[0079] 8 × 10 normal epidermal keratinocytes (NHEK(F)) 3After seeding cells / well into a 96-well plate, the cells were cultured at 37°C for 24 hours in HuMedia-KG2 medium (Kurashiki Boseki Co., Ltd.). After incubation, 1 mM or 2 mM of Compound 1 was added to the medium as a sample solution and further cultured for 48 hours. After incubation, immunodetection using MCSP antibody was performed. Specifically, after washing with PBS(-), the cells were fixed in 15% neutral buffered formalin for 30 minutes, permeabilized with 0.5% Triton X-100 solution for 1 hour, and blocked with 5x diluted Blocking One P (Nacalai Tesque) solution for 2 hours. After that, MCSP antibody was added and the plate was left to stand at room temperature for 1 hour. Next, the plate was washed with PBS(-), and a fluorescently labeled secondary antibody was added and the plate was left to stand in the dark for a certain period of time. After washing with PBS(-), the fluorescence intensity was measured. First, the fluorescent label of the secondary antibody (Alexa Fluor 488) was measured at Ex = 485 nm and Em = 520 nm using a fluorescence microplate reader (Fluoroscan Ascent, Thermo Fisher Scientific). DNA staining with Hoechst 33342 was then performed, and measurements were taken at Ex = 355 nm and Em = 460 nm. The MCSP expression level was calculated by dividing the Alexa Fluor 488 fluorescence intensity for each test group by the Hoechst 33342 fluorescence intensity. The same procedure was performed for a control group (PBS(-) without sample added). The relative value of the MCSP expression level obtained with each sample addition was calculated and used as the MCSP expression promotion level (%).

[0080] The results of Test Example 9 are shown in Table 9. [Table 9] JPEG0007788774000013.jpg82127

[0081] As shown in Table 9, it was confirmed that Compound 1 exhibits an MCSP expression-promoting effect. This suggests that it also has the effect of maintaining the stemness of epidermal cells. Furthermore, since Components 10, 14, and 28 also exhibit an MCSP expression-promoting effect, it is predicted that a synergistic effect of promoting MCSP expression will be exerted by using Compound 1 in combination with any one of Components 10, 14, and 28.

[0082] Test Example 10: Evaluation of various gene expression using three-dimensional models A three-dimensional skin model, TEST SKIN LSE-high (Roman Skin Lab, Inc.), was cultured according to standard methods. After 24 hours, an aqueous solution of Compound 1 (5% concentration) was added to the tissue, and the tissue was cultured for another day. A control model without any treatment was also cultured in the same manner. After the culture was completed, tissue from each test group was collected with 1 mL of Trizol reagent (Invitrogen). 200 μL of chloroform (Wako Pure Chemical Industries, Ltd.) was added to the collected tissue, mixed by stirring, and centrifuged in a centrifuge (TOMY / MX-160) at 15,000 rpm and 4°C for 15 minutes, after which 400 μL of the aqueous layer was removed. 500 μL of isopropanol (Wako Pure Chemical Industries, Ltd.) was added to the collected aqueous layer, mixed by stirring, and centrifuged at 15,000 rpm and 4°C for 15 minutes to obtain a total RNA precipitate. The total RNA was washed by adding 1 mL of 75% ethanol and vortexing. The mixture was then centrifuged at 15,000 rpm at 4°C for 15 minutes to recover the precipitate. The recovered total RNA was reverse-transcribed using a designated kit (PrimeScript RT reagent Kit with gDNA Eraser (Perfect Real Time) (Takara Bio Inc.)) to synthesize cDNA. Using this synthesized cDNA as a sample, expression of various target genes and the internal standard GAPDH gene were detected using the Thermal Cycler Dice® Real Time System Single (Takara Bio Inc.) and SYBR® Premix Ex Taq™ II (Perfect Real Time) (Takara Bio Inc.). GAPDH is a housekeeping gene (a gene expressed at a constant level in many tissues and cells, which is constantly expressed and essential for cell maintenance and proliferation). Because its expression level is always constant, it is used as an internal standard in PCR experiments. The test results were obtained by comparing the expression levels of various target genes in each test group when the expression level of the GAPDH gene was kept constant. In this test system, the expression level of each gene in the control group was set to 100, and the relative value of the expression level of that gene in the group to which Compound 1 was added was calculated.

[0083] The results of Test Example 10 are shown in Table 10. [Table 10] JPEG0007788774000014.jpg78143

[0084] As shown in Table 10, it was confirmed that Compound 1 enhances the expression of laminin α chain (LAMA1), which is involved in the binding of the basement membrane and epidermis and is also involved in epidermal turnover; sphingomyelinase 1 (SMPD1), which is involved in ceramide synthesis; occludin (OCLN) and claudin (CLDN), which are involved in the synthesis of tight junctions; type I collagen α1 chain (COL1A1), which is involved in dermal firmness; and type IV collagen α1 chain (COL4A1), a protein that constitutes the basement membrane and is involved in epidermal turnover. This suggests that Compound 1 contributes to moisturizing through its ceramide synthesis promotion effect, improvement of barrier function, firmness and wrinkle reduction through its collagen synthesis promotion effect, barrier function improvement through its tight junction synthesis promotion effect, and basement membrane care through its type IV collagen synthesis promotion effect.

[0085] Test Example 11. Evaluation of tyrosinase gene expression Normal melanocytes (NHEM) were cultured in DermaLife medium (Kurabo) at 6 × 10 4The cells were prepared at a concentration of 1 / mL, and 1 mL of each was seeded onto a 24-well plate and cultured at 37°C under 5% CO2 and saturated steam. After 24 hours of culture, a culture medium containing Compound 1 at a final concentration of 2 mM was added. A control group was also prepared by adding culture medium alone. After 24 hours of culture, cells from each group were harvested with 0.5 mL of Trizol reagent (Invitrogen). 100 μL of chloroform (Wako Pure Chemical Industries, Ltd.) was added to the harvested cells, mixed by stirring, and centrifuged at 15,000 rpm and 4°C for 15 minutes in a centrifuge (TOMY MX-160). 200 μL of the aqueous layer was then removed. 250 μL of isopropanol (Wako Pure Chemical Industries, Ltd.) was added to the harvested aqueous layer, mixed by stirring, and centrifuged at 15,000 rpm and 4°C for 15 minutes to obtain a total RNA precipitate. The total RNA was washed by adding 1 mL of 75% ethanol and vortexing. The mixture was then centrifuged at 15,000 rpm at 4°C for 15 minutes to recover the precipitate. The recovered total RNA was reverse-transcribed using a designated kit (PrimeScript RT reagent Kit with gDNA Eraser (Perfect Real Time) (Takara Bio Inc.)) to synthesize cDNA. Using the synthesized cDNA as a sample, expression of the tyrosinase gene and the internal standard β-actin gene were detected using the Thermal Cycler Dice® Real Time System Single (Takara Bio Inc.) and SYBR® Premi×E×Taq™ II (Perfect Real Time) (Takara Bio Inc.). β-actin is a housekeeping gene (a gene expressed at a constant level in many tissues and cells, which is constantly expressed and essential for cell maintenance and proliferation). Because its expression level is always constant, it is used as an internal standard in PCR experiments. The test results were compared by comparing the expression level of each gene in each test group, with the expression level of the β-actin gene set at 1.

[0086] The results of Test Example 11 are shown in Table 11. [Table 11] JPEG0007788774000015.jpg36141

[0087] As shown in Table 11, it was confirmed that Compound 1 inhibits the expression of the tyrosinase gene, suggesting that Compound 1 has an effect of improving pigmentation such as age spots and freckles by inhibiting tyrosinase activity.

[0088] Test Example 12. Evaluation of PAR2 gene expression Normal human epidermal cells were grown in HuMediaKG2 (Kurabo) containing a growth additive at 6 × 10 4The cells were prepared at a concentration of 1 / mL, and 1 mL of each was seeded onto a 24-well plate and cultured at 37°C under 5% CO2 and saturated steam. After 24 hours of culture, a culture medium containing Compound 1 at a final concentration of 5 mM was added. A control group was also prepared by adding culture medium alone. After 24 hours of culture, cells from each group were harvested with 0.5 mL of Trizol reagent (Invitrogen). 100 μL of chloroform (Wako Pure Chemical Industries, Ltd.) was added to the harvested cells, mixed by stirring, and centrifuged at 15,000 rpm and 4°C for 15 minutes in a centrifuge (TOMY MX-160). 200 μL of the aqueous layer was then removed. 250 μL of isopropanol (Wako Pure Chemical Industries, Ltd.) was added to the harvested aqueous layer, mixed by stirring, and centrifuged at 15,000 rpm and 4°C for 15 minutes to obtain a total RNA precipitate. The total RNA was washed by adding 1 mL of 75% ethanol and vortexing. The mixture was then centrifuged at 15,000 rpm at 4°C for 15 minutes to recover the precipitate. The recovered total RNA was reverse-transcribed using a designated kit (PrimeScript RT reagent Kit with gDNA Eraser (Perfect Real Time) (Takara Bio Inc.)) to synthesize cDNA. Using the synthesized cDNA as a sample, expression of the PAR2 gene and the internal standard β-actin gene were detected using the Thermal Cycler Dice® Real Time System Single (Takara Bio Inc.) and SYBR® Premi×E×Taq™ II (Perfect Real Time) (Takara Bio Inc.). β-actin is a housekeeping gene (a gene expressed at a constant level in many tissues and cells, which is constantly expressed and essential for cell maintenance and proliferation). Because its expression level is always constant, it is used as an internal standard in PCR experiments. The test results were compared by comparing the expression level of each gene in each test group, with the expression level of the β-actin gene set at 1.

[0089] The results of Test Example 12 are shown in Table 12. [Table 12] JPEG0007788774000016.jpg35141

[0090] As shown in Table 12, it was confirmed that Compound 1 inhibits the expression of the PAR2 gene, which is involved in the transfer of melanosomes from melanocytes to keratinocytes. This suggests that Compound 1 inhibits the transfer of melanosomes from melanocytes to keratinocytes and has an inhibitory effect on pigmentation.

[0091] Prescription example 1. Lotion [Ingredients] Part Eucalyptus oil 0.2 Polyoxyethylene (5.5) Cetyl Alcohol 5.0 This compound 1 5.0 Tocopherol acetate 0.02 Dipotassium glycyrrhizinate 0.5 Monoammonium glycyrrhizinate 0.5 Stearyl glycyrrhizinate 0.05 Isopropylmethylphenol 0.1 Align In 0.1 D-Pantothenyl alcohol 0.1 Salicylic acid 0.5 Urea 5.0 l-menthol 0.9 dl-menthol 0.2 1,3-butylene glycol 5.0 Sodium citrate 0.2 Methylparaben 0.1 Hinokitiol 0·003 Photosensor No. 201 0.002 Purified water (enough to make the total volume 100 parts)

[0092] Prescription example 2: Lotion [Ingredients] Part Glyceryl Caprylate 3.0 Polyglyceryl-10 Laurate 3.0 Cetyl alcohol 2.0 Behenyl Alcohol 2.0 Methylparaben 0.1 This compound 1 5.0 Yeast hydrolyzate 2.0 Ascorbic Acid 3.0 Glycyrrhizic acid 0.5 β-Glycyrrhetinic acid 0.05 Tocopherol nicotinate 0.1 Resorcinol 0.1 Zinc Oxide 2.0 dl-camphor 0.5 Glycerin 2.0 1,3-butylene glycol 5.0 Potassium hydroxide 0.5 Purified water (enough to make the total volume 100 parts)

[0093] Prescription example 3: Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of rice leaf hydrolysate was used in place of the yeast hydrolysate contained in Formulation Example 2.

[0094] Prescription example 4: Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of rice extract hydrolysate was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0095] Prescription example 5. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of rice bran extract hydrolysate was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0096] Prescription example 6. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of rice fermentation liquid was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0097] Prescription example 7. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of bamboo shoot skin extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0098] Prescription example 8. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of fermented Job's tears seeds were used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0099] Prescription example 9. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of sake lees extract derived from sake was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0100] Prescription example 10. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of white mustard hydrolysate was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0101] Prescription example 11. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Benifuuki tea extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0102] Prescription example 12. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of honey-scented black tea extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0103] Prescription example 13. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of damask rose flower extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0104] Prescription example 14. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of peach flower extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0105] Prescription example 15. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of immature peach fruit extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0106] Prescription example 16. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of apricot fruit extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0107] Prescription example 17. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of cherry blossom extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0108] Prescription example 18. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of peony flower extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0109] Prescription example 19. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of peony root extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0110] Prescription example 20. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Salicornia herbacea extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0111] Prescription example 21. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of eelgrass extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0112] Prescription example 22. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that the yeast hydrolysate of Production Example 1 contained in Formulation Example 2 was replaced with 2.5 parts of water-soluble collagen and 2.5 parts of hydrolyzed collagen.

[0113] Prescription example 23. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of fermented black soybean was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0114] Prescription example 24. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of black soybean hydrolysate was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0115] Prescription example 25. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of fermented soy milk was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0116] Prescription example 26. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of adzuki bean extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0117] Prescription example 27. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of red clover root extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0118] Prescription example 28. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of pueraria lobata root extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0119] Prescription example 29. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of burdock root extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0120] Prescription example 30. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of sunflower sprout extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0121] Prescription example 31. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Mugwort leaf extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0122] Prescription example 32. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of chamomile extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0123] Prescription example 33. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of arnica flower extract was used instead of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0124] Prescription example 34. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of gentian extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0125] Prescription example 35. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of hibiscus flower fermentation product was used instead of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0126] Prescription example 36. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of perilla leaf extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0127] Prescription example 37. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Veronica purpurea fruit extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0128] Prescription example 38. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of lotus seed extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0129] Prescription example 39. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of lotus seed fermentation product was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0130] Prescription example 40. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of loofah extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0131] Prescription example 41. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of ginseng extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0132] Prescription example 42. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of eggplant fruit extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0133] Prescription example 43. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of pau d'arco bark extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0134] Prescription example 44. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of unripe kiwi fruit extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0135] Prescription example 45. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Morus alba extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0136] Prescription example 46. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of mulberry fruit extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0137] Prescription example 47. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of fig bark extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0138] Prescription example 48. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of a hydrolysate of Codonopsis ginseng root extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0139] Prescription example 49. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of jujube fruit extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0140] Prescription example 50. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of saffron flower extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0141] Prescription example 51. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of a mixture of mango fruit extract, mangosteen fruit extract, and cherimoya fruit extract was used instead of the yeast hydrolysate of Preparation Example 1 contained in Formulation Example 2.

[0142] Prescription example 52. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of bergamot fruit extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0143] Prescription example 53. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of immature grapefruit extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0144] Prescription example 54. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Banpeiyu fruit extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0145] Prescription example 55. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Japanese pepper seed extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0146] Prescription example 56. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of a daylily flower or bud extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0147] Prescription example 57. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of a daylily flower or bud extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0148] Prescription example 58. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of a fermented product of daylily flowers or buds was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0149] Prescription example 59. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Casablanca flower or bud extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0150] Prescription example 60. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Madonna lily flower or bud extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0151] Prescription Example 61. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of a lily of the valley flower or bud extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0152] Prescription Example 62. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of a Rhodiola rosea (Rhodiola tenuifolia) fermentation product was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0153] Prescription Example 63. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of jasmine flower extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0154] Prescription Example 64. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Juniperus communis fruit extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0155] Prescription Example 65. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of guava leaf extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0156] Prescription Example 66. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Bletilla striata root extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0157] Prescription Example 67. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of sweet potato shochu lees extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0158] Prescription example 68. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of white asparagus extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0159] Prescription Example 69. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of kelp extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0160] Prescription example 70. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Ulva extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0161] Prescription example 71. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Eucheuma mume extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0162] Prescription Example 72. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of Funori extract was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0163] Prescription Example 73. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of red ginseng extract was used instead of the yeast hydrolysate of Preparation Example 1 contained in Formulation Example 2.

[0164] Prescription example 74. Lotion A lotion was obtained in the same manner as in Formulation Example 2, except that 2.0 parts of ginseng fermentation product was used in place of the yeast hydrolysate of Production Example 1 contained in Formulation Example 2.

[0165] Prescription example 75. Lotion [Ingredients] Part Jojoba oil 1.0 Polyoxyethylene (5.5) Cetyl Alcohol 5.0 Methylparaben 0.1 This compound 1 5.0 Ascorbic Acid Glucoside 2.0 Tranexamic acid 2.0 ε-aminocaproic acid 0.1 Sulfur 0.2 Estradiol 0.1 Pyridoxine hydrochloride 0.5 Glycerin 5.0 1,3-butylene glycol 5.0 Sodium citrate 0.2 Sodium metabisulfite 0.2 d-Camphor 0.1 Purified water (enough to make the total volume 100 parts)

[0166] Prescription Example 76. Emulsion [Ingredients] Part Squalane 5.0 Cyclopentanesiloxane 1.0 Hexalan 3.0 Hexyldecyl Isostearate 1.0 Caprylic / Capric Triglyceride 1.0 Polyglyceryl-10 Laurate 5.0 Polyglyceryl-10 Isostearate 5.0 Ascorbyl dipalmitate 15.0 Hydrogenated soy lecithin 1.5 This compound 1 2.0 Ascorbic acid phosphate magnesium salt 3.0 Arbutin 3.0 Potassium hydroxide 0.5 Glycerin 3.0 1,3-butylene glycol 2.0 Carboxymethylcellulose 0.3 Xanthan gum 0.2 Tremella fuciformis polysaccharide 0.2 Sodium hyaluronate 0.01 Tocopherol acetate 0.3 Tocopherol nicotinate 0.1 Glycyrrhizic acid 0.1 Dipotassium glycyrrhizinate 0.1 Isopropylmethylphenol 0.1 Water-soluble collagen 1.0 Hydrolyzed Collagen 1.0 Sodium hyaluronate 1.0 Fermented ginseng root 1.0 Panax ginseng root extract 1.0 Hibiscus flower fermented liquid 1.0 Fermented Job's Tears Seeds 1.0 Zanthoxylum seeds hydrolysate 0.5 Rice bran extract hydrolyzate 0.5 Purified water (enough to make the total volume 100 parts)

[0167] Prescription Example 77. Emulsion An emulsion was obtained in the same manner as in Formulation Example 74, except that 2.0 parts of L-ascorbic acid-2-glucoside was used in place of 2.0 parts of ascorbic acid phosphate magnesium salt in Formulation Example 76.

[0168] Prescription Example 78. Emulsion An emulsion was obtained in the same manner as in Formulation Example 74, except that of the ingredients in Formulation Example 76, 2.0 parts of ascorbic acid phosphate magnesium salt and 0.5 parts of potassium hydroxide were replaced with 2.0 parts of tranexamic acid.

[0169] Prescription Example 79. Emulsion An emulsion was obtained in the same manner as in Formulation Example 74, except that 2.0 parts of ascorbic acid phosphate magnesium salt in Formulation Example 76 was replaced with 3.0 parts of 3-O-ethyl ascorbic acid.

[0170] Prescription example 80. Cream [Ingredients] Part Olive oil 5.0 Jojoba oil 5.0 Squalane 5.0 Hexyldecyl Isostearate 5.0 Dioctyldodecyl / Phytosteryl Lauroyl Glutamate / Behenyl) 5.0 Glyceryl Caprylate 1.0 Glyceryl stearate 1.0 Isostearyl glyceryl 3.0 γ-oryzanol 0.1 Behenyl Alcohol 2.0 Palmitic acid 2.5 D-Pantothenyl Alcohol 3.0 Allantoin 0.1 Riboflavin 0.01 Resorcinol 0.1 Benzalkonium chloride 0.05 Urea 3.0 β-Glycyrrhetinic acid 0.1 Stearyl Glycyrrhetinate 0.1 Ammonium glycyrrhizinate 0.1 This compound 1 3.0 Lactic acid bacteria fermented rice 2.0 Hydrogenated lecithin 0.5 Hydrogenated lysolecithin 0.5 Oil-soluble Panax ginseng extract 2.0 Sweet potato shochu lees liquid 1.0 Guava Leaf Extract 1.0 Hydrolyzed Rice Extract 2.0 Fermented rice liquid 1.0 Water-soluble collagen 1.0 Hydrolyzed Collagen 1.0 Xanthan gum 1.0 Zinc oxide 0.5 dl-camphor 0.3 l-menthol 0.5 Purified water (enough to make the total volume 100 parts)

[0171] Example 81. Pack Dipropylene Glycol 5.0 Polyoxyethylene (60) hydrogenated castor oil 5.0 Cetyl alcohol 3.0 Behenyl Alcohol 3.0 Allantoin 0.1 Dipotassium glycyrrhizinate 0.1 Ammonium glycyrrhizinate 0.1 β-Glycyrrhetinic acid 0.1 Stearyl Glycyrrhetinate 0.1 Salicylic acid 0.1 Tocopherol acetate 0.5 Tocopherol nicotinate 0.1 D-Pantothenyl alcohol 0.3 Resorcinol 0.1 Sulfur 2.0 Estradiol 0.002 This compound 1 3.0 Yeast hydrolyzate 3.0 Water-soluble collagen 1.0 Panax ginseng root (red ginseng) extract 1.0 Sunflower Sprout Extract 1.0 Guava Leaf Extract 1.0 Xanthan gum 2.0 Polyglyceryl-6 Myristate 1.0 Potassium cocoyl glutamate 1.0 Hydrogenated Lecithin 3.0 Hydroxylated Lecithin 3.0 Purified water (enough to make the total volume 100 parts)

[0172] Prescription example 82. Hair shampoo [Ingredients] Part Sodium Laureth Sulfate 10.0 Glyceryl Monostearate 1.0 Coconut oil fatty acid diethanolamide 2.0 Polyoxyethylene (40) hydrogenated castor oil 0.5 Benzalkonium chloride 1.0 Stearyl Alcohol 2.0 Behenyl Alcohol 2.0 Dimethicone 3.0 This compound 1 3.0 Allantoin 0.1 Dipotassium glycyrrhizinate 0.1 Salicylic acid 0.1 Sodium salicylate 0.1 Tocopherol acetate 0.1 Pyrithione Zinc 0.3 Benzoic acid 0.2 Triclosan 0.2 Citric acid 0.1 Propylene Glycol 2.0 Kelp extract 1.0 Burdock extract 1.0 Arrowroot extract 1.0 Eelgrass extract 1.0 Tamasakizukuraffe Root Extract 0.01 Panax ginseng extract 0.1 Eelgrass extract 1.0 Bamboo shoot peel extract 1.0 Pau d'Arco Bark Extract 1.0 Black rice hydrolysate 1.0 Purified water (enough to make the total volume 100 parts)

[0173] Example 83. Hair conditioner [Ingredients] Part Polyoxyethylene (10) hydrogenated castor oil 1.0 Distearyldimethylammonium chloride 1.5 Stearyltrimethylammonium chloride 2.0 Glyceryl 2-ethylhexanoate 1.0 Benzalkonium chloride 1.0 Cetyl alcohol 3.0 Stearyl Alcohol 1.0 This compound 1 3.0 Salicornia extract 1.0 Black soybean hydrolysate 1.0 Fermented soy milk 1.0 Fermented black soybeans 1.0 Allantoin 0.1 Isopropylmethylphenol 0.1 Dipotassium glycyrrhizinate 0.1 Salicylic acid 0.1 Sulfur 0.5 Alkylisoquinolinium bromide solution (75%) 0.06 Pyrithione Zinc 0.3 Methylparaben 0.1 Triclosan 0.2 Resorcinol 0.1 Purified water (enough to make the total volume 100 parts)

[0174] Formulation example 84. Cleansing cosmetics [Ingredients] Part Potassium cocoyl glycinate 5.0 Glycerin 10.0 Glyceryl Caprylate 1.0 Sodium lauroyl aspartate 10.0 Water-soluble collagen 5.0 Cetyl alcohol 3.0 Myristyl Alcohol 3.0 Fermented Job's Tears Seeds 2.0 Isopropyl methyl alcohol 0.1 Allantoin 0.1 Sulfur 0.5 Glycyrrhizic acid 0.1 Dipotassium glycyrrhizinate 0.1 Monoammonium glycyrrhizinate 0.1 β-Glycyrrhetinic acid 0.05 Stearyl Glycyrrhetinate 0.1 Salicylic acid 0.2 Tocopherol acetate 0.2 Triclosan 0.1 Trichlorocarbanide 0.5 Trichlorohydroxydiphenyl ether 0.2 Concentrated Benzalkonium Chloride Solution 50 0.2 Benzalkonium chloride 0.1 Panax ginseng root (red ginseng) 0.5 Purified water (enough to make the total volume 100 parts)

[0175] Prescription example 85. Sheet mask A sheet mask is obtained by impregnating a nonwoven fabric with the following ingredients. [Ingredients] Part This compound 1 3.0 Glycerin 3.0 1,3-butylene glycol 2.0 L-Ascorbic Acid 2-Glucoside 2.0 Methylparaben 0.2 Citric acid 0.1 Sodium citrate 0.3 Xanthan gum 1.0 Water-soluble collagen 1.0 Sodium hyaluronate 1.0 Eelgrass extract 1.0 Rice extract hydrolyzate 1.0 Potassium hydroxide (appropriate amount) Purified water (enough to make the total volume 100 parts)

[0176] Prescription example 86. Beauty serum [Ingredients] Part Ethanol 2.0 Glycerin 5.0 1,3-butylene glycol 5.0 Methylparaben 0.1 Hyaluronic Acid Hydrolysate 1.0 Hyaluronic acid lactic acid bacteria fermentation product 1.0 Lotus Seed Extract 1.0 Lactic acid bacteria culture 1.0 Cherry blossom extract 1.0 Sake lees extract 1.0 Peony root extract 1.0 Peach kernel extract 1.0 Soo leaf extract 1.0 Chamomile flower extract 1.0 Kelp extract 1.0 Ulva extract 1.0 Eucheuma muscaria extract 1.0 Citric acid 0.3 Sodium citrate 0.6 Purified water (enough to make the total volume 100 parts)

Claims

1. An agent for preventing or improving epidermal thinning, which contains pyridine-3-carboxylic acid amide as an active ingredient.

2. An agent for preventing or improving epidermal thinning, which further comprises one or more of eggplant extract and barberry fruit extract, in the agent described in claim 1.

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