External preparation for skin

Abstract

To provide a skin care preparation which is derived from a natural product, is excellent in biological safety, and exhibits functions of preventing or improving skin roughness, improving the transparency of the skin, and suppressing cell aging by suppressing the secretion of inflammatory substances (cytokine and chemokine) in the skin.SOLUTION: An extract of Gentiana lutea belonging to the genus Gentiana of the family Gentianaceae and an extract of Bletilla striata belonging to the genus Bletilla of the family Orchidaceae are used as active ingredients for suppressing the secretion of inflammatory factor (cytokine and chemokine).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an active ingredient that can be incorporated into external skin preparations and has the effect of preventing or improving rough skin, cellular aging, and pigmentation such as age spots, freckles, and dullness. [Background technology]

[0002] Previously, external factors such as cell and tissue damage caused by reactive oxygen species induced by sunlight (ultraviolet rays) and chemicals (nitrogen compounds, sulfur compounds, etc.) contained in exhaust gases, as well as inflammation, have been known to cause a decline in skin barrier function, rough skin, and pigmentation. Furthermore, inflammatory substances (cytokines or chemokines) secreted from cells in the skin due to the effects of ultraviolet rays, etc., have attracted attention as causes of the decline in skin barrier function, rough skin, and pigmentation, and research is underway to suppress rough skin, a decline in barrier function, and blemishes by inhibiting the expression and secretion of cytokines or chemokines. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 04-005237 [Patent Document 2] Japanese Patent Application Publication No. 06-024937 [Patent Document 3] Japanese Patent Application Publication No. 07-252128 [Patent Document 4] Japanese Patent Application Laid-Open No. 2002-205933 [Patent Document 5] International Publication No. 2019 / 078370 DISCLOSURE OF THE INVENTION [Problem to be solved by the invention]

[0004] In view of the above background art, the present inventors have conducted extensive research to discover new active ingredients. As a result, they have newly discovered that a combination of an extract of Gentiana serrata (Gentianaceae, Gentianaceae) and an extract of Striata serrata (Orchidaceae), or a combination of an extract of Gentiana serrata and an extract of Striata serrata with glycyrrhizinic acid or its derivatives, or glycyrrhetinic acid or its derivatives, significantly inhibits the secretion of inflammatory substances (cytokines and chemokines). Furthermore, they have newly discovered that a combination of an extract of Gentiana serrata and an extract of Striata serrata with tranexamic acid or its derivatives, or ascorbic acid or its derivatives, significantly prevents or improves pigmentation.

[0005] It has been known that gentian extract, Bletilla serrata extract, or glycyrrhizinic acid or its derivatives can be used alone as a topical skin ingredient (Patent Documents 1 to 5), but it was not known that a combination of gentian extract and Bletilla serrata extract, or a combination of gentian extract and Bletilla serrata extract with glycyrrhizinic acid or its derivative, or glycyrrhetinic acid or its derivative, significantly suppresses the expression of inflammatory substances (cytokines and chemokines).Furthermore, it was not known that a combination of gentian extract and Bletilla serrata extract with tranexamic acid or its derivative, or ascorbic acid or its derivative, significantly prevents or improves pigmentation. [Means for solving the problem]

[0006] The present invention relates to an external skin preparation containing an extract of Gentiana gentiana (Gentianaceae, Gentianaceae) and an extract of Bletilla striata (Orchidaceae, Orchidaceae) as active ingredients. Furthermore, the present invention preferably further comprises, as an active ingredient, one or more of glycyrrhizinic acid or a derivative thereof, glycyrrhetinic acid or a derivative thereof, tranexamic acid or a derivative thereof, and ascorbic acid or a derivative thereof. [Effects of the Invention]

[0007] The present invention provides an external skin preparation that significantly suppresses the secretion of inflammatory substances (cytokines and chemokines) from cells, thereby preventing or improving rough skin, preventing cellular aging, and preventing or improving pigmentation, by using a combination of a gentian extract and a Bletilla striata extract as active ingredients, or a combination of a gentian extract and a Bletilla striata extract of the Orchidaceae family with one or more of glycyrrhizinic acid or a derivative thereof, glycyrrhetinic acid or a derivative thereof, tranexamic acid or a derivative thereof, and ascorbic acid or a derivative thereof as active ingredients. DETAILED DESCRIPTION OF THE INVENTION

[0008] In the present invention, "gentian" refers to Gentiana lutea of ​​the genus Gentiana in the family Gentianaceae. In the present invention, the whole plant, flowers, stems, leaves, roots, etc. can be used.

[0009] The term "Bletilla striata" as used in the present invention refers to the purple orchid Bletilla striata (THUNB.) REICHB.fil, a plant of the Orchidaceae family. In the present invention, the bulb of this Bletilla striata, i.e., the Chinese herbal medicine Baiqi, is preferably used.

[0010] To prepare the extract, first, the part of each plant to be used is washed with water if necessary to remove foreign matter, and then, either as is or dried, is shredded or crushed as necessary, and then brought into contact with an extracting solvent for extraction. Extraction can be carried out by contacting with the extracting solvent according to a conventional method such as the immersion method.

[0011] Examples of extraction solvents include water; lower alcohols such as methanol, ethanol, and propanol; polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, and glycerin; esters such as ethyl acetate, butyl acetate, and methyl propionate; 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, and these may be used alone or in combination.

[0012] Among the above-mentioned extraction solvents, hydrophilic solvents such as water, lower alcohols, or polyhydric alcohols are preferred in the present invention from the viewpoints of the efficacy of the resulting extract, skin irritation, and the wide range of applications for topical skin preparations (cosmetics, quasi-drugs, etc.). Preferred examples of hydrophilic solvents include the use of water, lower alcohols (particularly ethanol), or polyhydric alcohols (particularly 1,3-butylene glycol) alone, or a mixed solvent of water and a lower alcohol (particularly ethanol), or a mixed solvent of water and a polyhydric alcohol (particularly 1,3-butylene glycol, glycerin).

[0013] When a mixed solvent is used, the mixing ratio is preferably in the range of, for example, a volume ratio (same hereinafter) of 1:99 to 99:1 for a mixed solvent of water and 1,3-butylene glycol, 1:25 to 25:1 for a mixed solvent of water and ethanol, or 1:20 to 20:1 for a mixed solvent of water and glycerin.

[0014] The weight ratio of the part of each plant to be used to the extraction solvent is generally 1:1 to 1:50.

[0015] When preparing the extract solution, the pH is not particularly limited, but is generally preferably in the range of 3 to 9. In this sense, if necessary, the extract solvent may be blended with an alkalinity adjuster such as sodium hydroxide, sodium carbonate, potassium hydroxide, sodium hydrogen phosphate, or sodium phosphate, or an acidity adjuster such as citric acid, hydrochloric acid, phosphoric acid, malic acid, or sulfuric acid to adjust the pH to the desired level.

[0016] The extraction conditions, such as extraction temperature and extraction time, vary depending on the type and pH of the solvent used. For example, when water, 1,3-butylene glycol, or a mixture of water and 1,3-butylene glycol is used as the solvent, the extraction temperature is preferably in the range of 0°C to 80°C, more preferably in the range of 0°C to 20°C, and the extraction time is preferably in the range of 1 to 168 hours (1 hour to 1 week), more preferably in the range of 1 to 120 hours (1 hour to 5 days).

[0017] The extract solutions prepared as described above are mixed and generally adjusted to a pH of 3 to 8. The mixture may be used as an ingredient in a topical skin preparation as is, or may be used at a desired concentration by vacuum concentration, etc. The extract may also be dried by a conventional method such as spray drying.

[0018] The solid content concentration of the gentian extract according to the present invention is preferably 0.01 to 5.0% by weight in the extract solution. The solid content concentration of the Bletilla striata extract according to the present invention is preferably 0.01 to 5.0% by weight in the extract solution. The blending ratio of the gentian extract to the Bletilla striata extract is preferably 1:10 to 10:1 in terms of solid content.

[0019] In the present invention, in addition to the above extract, glycyrrhizinic acid or a derivative thereof (dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc.), or glycyrrhetinic acid or a derivative thereof (β-glycyl, stearyl glycyrrhetinate, etc.) may be used in combination. Note that, as the glycyrrhizinic acid or a derivative thereof, or glycyrrhetinic acid or a derivative thereof, commercially available products may be used, or glycyrrhetinic acid contained in an extract of a plant such as Glycyrrhiza uralensis or Glycyrrhiza glabra of the Leguminosae family may be used, or glycyrrhetinic acid derived from licorice may be processed into dipotassium glycyrrhizinate, β-glycyrrhetinic acid, or stearyl glycyrrhetinate by a conventional method and used.

[0020] In the present invention, the concentration of glycyrrhizinic acid or a derivative thereof (such as dipotassium glycyrrhizinate) or glycyrrhetinic acid or a derivative thereof (such as β-glycyrrhetinic acid or stearyl glycyrrhetinate) in the external skin preparation is preferably 0.001% to 1.0% by weight.

[0021] In the present invention, ascorbic acid or a derivative thereof may be used in combination with the above extract. Examples of ascorbic acid derivatives include ascorbic acid ester salts such as 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 6-acylated products of these ascorbic acid sugar derivatives (acyl Examples of the group include a hexanoyl group, an octanoyl group, a decanoyl group, etc.), 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.

[0022] In the present invention, the concentration of ascorbic acid or a derivative thereof in the external skin preparation is preferably 0.001% to 10.0% by weight.

[0023] In addition to the above extract, tranexamic acid or a derivative thereof [tranexamic acid esters (e.g., tranexamic acid lauryl ester, tranexamic acid hexadecyl ester, tranexamic acid cetyl ester, or salts thereof), tranexamic acid amides (e.g., tranexamic acid methylamide)] may be used in combination.

[0024] In the present invention, the concentration of tranexamic acid or a derivative thereof in the external skin preparation is preferably 0.001% to 5.0% by weight.

[0025] Examples of topical skin preparations (cosmetics, quasi-drugs, etc.) containing the extract of the present invention include milky lotions, creams, lotions, essences, transparent gels, packs, lipsticks, foundations, sheet masks, liquid foundations, makeup press powders, blushers, face powders, facial cleansers, body shampoos, hair shampoos and conditioners, and cleansing cosmetics such as soaps.

[0026] When the extract of the present invention is incorporated into topical skin preparations (cosmetics, quasi-drugs, etc.), ingredients used in topical skin preparations, such as oily ingredients, surfactants (synthetic or natural), moisturizers, thickeners, emulsifiers or emulsifier aids, preservatives / bactericides, powder ingredients, UV absorbers, antioxidants, pigments, fragrances, anti-wrinkle agents, and other physiologically active ingredients, can be appropriately incorporated as needed. Furthermore, as long as the efficacy and characteristics of the extract of the present invention are not impaired, it is also acceptable to incorporate the extract of the present invention in combination with other physiologically active ingredients into topical skin preparations.

[0027] Examples of oily components include olive oil, jojoba oil, castor oil, soybean oil, rice oil, rice germ oil, coconut oil, palm oil, cocoa 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, paraffin wax, Examples include hydrocarbons such as 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).

[0028] 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 ethylene 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.

[0029] Examples of emulsifiers 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.), and the like.

[0030] 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 or its salts or derivatives, hyaluronic acid hydrolyzate, chondroitin or its derivatives, heparin or its derivatives, etc.), elastin and its derivatives, collagen and its derivatives, lactic acid, urea, and higher fatty acid octyldodecyl.

[0031] 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.

[0032] Examples of anti-inflammatory agents include allantoin, monoammonium glycyrrhizinate, ε-aminocaproic acid, d-camphor, dl-camphor, zinc oxide, D-pantothenyl alcohol, pyridoxine or a salt thereof, and riboflavin or a derivative thereof.

[0033] 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, alkylisoquinolinium bromide, resorcinol, Jamal (imidazoline urea), isopropylmethylphenol, triclosan, trichlorocarbanide, trichlorohydroxydiphenol ether, hinokitiol, 1,2-pentanediol, propanediol, hexanediol, concentrated benzalkonium chloride solution 50, and essential oils such as peppermint oil and eucalyptus oil.

[0034] Examples of cell activators include D-pantothenyl alcohol, menthol, dl-menthol, and γ-oryzanol.

[0035] Anti-acne agents include, for example, sulfur, salicylic acid or its salts, photosensitizer No. 201, pyridoxine dicaprylate, and isopropylmethylphenol.

[0036] 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.

[0037] Examples of ultraviolet absorbers include ethyl para-aminobenzoate, ethylhexyl para-dimethylaminobenzoate, amyl salicylate and its derivatives, 2-ethylhexyl para-methoxycinnamate, 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.

[0038] 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.

[0039] Examples of whitening agents include one or more selected from kojic acid and its derivatives, hydroquinone or its derivatives, ellagic acid and its derivatives, resorcinol derivatives, nicotinic acid and its derivatives, 4-methoxysalicylic acid potassium salt, magnolignan (5,5'-dipropyl-biphenyl-2,2'-diol), hydroxybenzoic acid and its derivatives, vitamin E and its derivatives, alpha-hydroxy acid, AMP (adenosine monophosphate, adenosine monophosphate), linoleic acid, t-cycloamino acid derivatives, mulberry bark extract, chamomile extract, hydrolyzed rice bran extract, saxifrage extract, and white mustard extract or hydrolyzates thereof.

[0040] Examples of kojic acid derivatives 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. Examples of hydroquinone derivatives include arbutin (hydroquinone-β-D-glucopyranoside) and α-arbutin (hydroquinone-α-D-glucopyranoside). Examples of resorcinol derivatives include 4-n- Examples of 2,5-dihydroxybenzoic acid derivatives include 2,5-diacetoxybenzoic acid, 2-acetoxy-5-hydroxybenzoic acid, and 2-hydroxy-5-propionyloxybenzoic acid. Examples of nicotinic acid derivatives include nicotinamide (niacinamide) and benzyl nicotinate. Examples of vitamin E or its derivatives include tocopherol acetate and sodium α-tocopheryl phosphate. Examples of α-hydroxy acids include lactic acid, malic acid, succinic acid, citric acid, and α-hydroxyoctanoic acid.

[0041] Anti-wrinkle agents include vitamin A or its derivatives, niacinamide, vitamin E or its derivatives (tocopherol acetate, etc.), vitamin C or its derivatives (ascorbic acid glucoside, 3-O-ethyl ascorbic acid, ascorbic acid phosphate magnesium salt, etc.), pantothenyl alcohol, tranexamic acid, etc.

[0042] Furthermore, it is also possible to use in combination components derived from natural products such as the following plants or microorganisms. For example, collagen or its hydrolysate, yeast extract or hydrolysate, lactic acid bacteria culture, grasses, cruciferous plants, Theaceae plants, Rosaceae plants, Paeoniaceae plants, Rutaceae plants, Amaranthaceae plants, Zosteraea plants, Leguminosae plants, Asteraceae plants, Fabaceae plants, Malvaceae plants, Gentianaceae plants, Lamiaceae plants, Nelumbaceae plants, Cucurbitaceae plants, Araliaceae plants, Solanaceae plants, Bignoniaceae plants, Mulberry plants, Iridaceae plants, Campanulaceae plants, Oleaceae plants, Actinidiaceae plants, Mulberry plants, Rhamnaceae plants, Orchidaceae plants, Anacardiaceae plants, Fructaceae plants, and the like. Examples of suitable extracts include extracts of one or more plants selected from the family Pinaceae, Valencaceae, Rutaceae, Myrtaceae, Liliaceae, Crassulaceae, Cupressaceae, Convolvulaceae, and Asparagaceae, or hydrolysates or fermented products thereof; extracts of one or more seaweeds selected from the family Laminariaceae, 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.

[0043] The present invention will now be described in more detail with reference to Production Examples, Test Examples, and Formulation Examples, but the present invention is not limited thereto. In the following, all parts mean parts by weight, and all % mean % by weight.

[0044] Preparation Example 1. Preparation of gentian extract 14 g of gentian powder, prepared by drying gentian roots (which may include stems), was added to 1000 g of 30% 1,3-butylene glycol aqueous solution and extracted for 18 hours at 4°C. This was filtered to obtain 903 g of gentian extract (solid concentration 2.05%).

[0045] Preparation Example 2. Preparation of Bletilla striata extract 100 g of finely chopped Bletilla striata bulbs were mixed with 900 g of purified water, and the mixture was extracted at 80°C for 3 hours, followed by filtration to obtain 510 g of a pale yellow, transparent extract solution (solid concentration 2.3%).

[0046] The preparation of the gentian extract and Bletilla striata extract according to the present invention is not limited to the methods shown in Production Examples 1 and 2 above. The extract can also be prepared using a solvent having the same polarity as the solvent used in Production Examples 1 and 2, such as water alone, a mixed solvent of water and 1,3-butylene glycol, a mixed solvent of water and 1,3-propanediol, a mixed solvent of water and pentanediol, or a mixed solvent of water and a polyhydric alcohol such as a mixed solvent of water and glycerin, or a mixed solvent of water and a lower alcohol such as ethanol, by adjusting the temperature and pH as appropriate.

[0047] Test Example 1. Evaluation test of cytokine and chemokine secretion inhibitory effect Human epidermal keratinocytes (NHEK) were seeded onto a 96-well plate and cultured for one day in HuMedia KG2 medium (Kurabo) under standard culture conditions. The control solution and compositions 1 to 3 shown in Table 1 were then added as sample solutions, and the cells were cultured for another day. The concentrations of the extracts of Preparation Examples 1 and 2 according to the present invention in the sample solutions were adjusted so that the final concentrations of the extracts in the solution relative to the total volume of the medium were 2.0%. The culture medium was then removed, PBS(-) was added, and ultraviolet light (UV-B) was applied at approximately 50 mJ / cm. 2 The cells were irradiated under the conditions shown in Table 1. Next, the PBS(-) was replaced with culture medium (HuMedia KG2) and cultured for another day. After the culture was completed, the culture medium was collected, and the increase or decrease in inflammatory substances (cytokines and chemokines) was detected using a chemiluminescence detector (ATTO) by membrane array analysis using a commercially available antibody array kit (Abcam). In parallel, a control solution containing 30% 1,3-butylene glycol (30% BG solution) at the same concentration as the sample solution was added instead of the sample solution. Controls with and without UV irradiation (UV-irradiated control) were also set up, and cytokines and chemokines in the culture supernatant were measured in the same manner. The evaluation results were expressed as relative values, with the UV-irradiated control set at 100.

[0048] The sample solutions (control solution, compositions 1 to 3) used in Test Example 1 are shown in Table 1. In Table 1, the test area irradiated with UV is indicated as UV(+), and the test area not irradiated with UV is indicated as UV(-). [Table 1] JPEG2026012845000001.jpg110138

[0049] The results of evaluation of the inhibition of cytokine secretion by the method of Test Example 1 are shown in Table 2. [Table 2] JPEG2026012845000002.jpg70138

[0050] As shown in Table 2, it was confirmed that composition 1 containing the extract of the present invention significantly suppressed cytokine secretion compared to the control. It was also confirmed that composition 2 containing the extract of the present invention significantly suppressed cytokine secretion compared to the control and composition 3. This confirms that compositions 1 and 2 containing the extract of the present invention are useful as components that suppress cytokine secretion and prevent or improve rough skin. Furthermore, Table 2 shows that transforming growth factor-1β (TGF-1β), interleukin-1α (IL-1α), and interleukin-6 (IL-6) are known to be factors that cause inflammation as well as factors secreted by senescent cells that induce senescence in other cells. This suggests that compositions 1 and 2 containing the extract of the present invention are effective components that suppress cellular senescence by suppressing the secretion of these factors.

[0051] The results of the evaluation of chemokine secretion inhibition according to the method of Test Example 1 are shown in Table 3. [Table 3] JPEG2026012845000003.jpg78139

[0052] As shown in Table 3, composition 1 containing the extract of the present invention was confirmed to significantly suppress chemokine secretion compared to the control. Furthermore, composition 2 containing the extract of the present invention was confirmed to significantly suppress chemokine secretion compared to the control and composition 3. This confirms that compositions 1 and 2 containing the extract of the present invention are useful as components that suppress chemokine secretion, inhibit inflammatory cell migration, and prevent or improve rough skin. Furthermore, Table 3 shows that growth-regulated oncogene α (GRO-α [CXCL1]), growth-regulated oncogene (GRO), interleukin 8 (IL-8), neutrophil peptide 78 (ENA-78 [CXCL5]), and monocyte chemotactic protein 3 (MCP-3 [CCL7]) are known to not only cause inflammation but also be secreted by senescent cells and induce senescence in other cells. This suggests that compositions 1 and 2 containing the extract of the present invention are effective components that suppress cellular senescence by suppressing the secretion of these factors.

[0053] In the above Test Example 1, composition 2 containing the extracts according to Production Examples 1 and 2 of the present invention and dipotassium glycyrrhizinate was evaluated, but the present invention is not limited to this, and β-glycyrrhetinic acid or stearyl glycyrrhetinate may be combined with dipotassium glycyrrhizinate and incorporated into a topical skin preparation. β-Glycyrrhetinic acid or stearyl glycyrrhetinate can also be expected to have the effect of suppressing the secretion of cytokines and chemokines when combined with the extract according to the present invention, and are particularly suitable for incorporation into oil-soluble topical skin preparations.

[0054] Test Example 2: Evaluation of the effect of suppressing ROS in epidermal cells Normal human epidermal keratinocytes (NHEK) were cultured at 8 × 10 4The cells were prepared at a concentration of 100 μL / mL, and 100 μL was seeded on a 96-well microplate. The cells were cultured at 37°C under 5% CO2 and saturated steam. After 24 hours, a culture medium containing compositions 1 and 4 according to the present invention (containing ascorbic acid glucoside as an ascorbic acid derivative) was added as a sample solution, and the cells were cultured. In addition, a test group to which a culture medium containing the same concentration of PBS(-) was added instead of the sample solution was set as a control and used as a comparison group. After 24 hours, the supernatant from the test group was removed, and the reagent "2',7'-dichlorodihydrofluorescein diacetate (DCFH-2DA)" was taken up by the cells, followed by washing with HBSS. The cells were then irradiated with approximately 50 mJ / cm2 of UV-B light from the bottom of the incubator using a UV-B lamp (Philips TL20W / 12RS). 2 The cells were then exposed to UV light for 100 seconds. Fluorescence intensity (excitation wavelength: 485 nm, absorption wavelength: 538 nm) was then measured using a fluorescent plate reader (Varioskan™ LUX, Thermo Scientific) and used as the ROS generation rate. The test results were expressed as a relative value (ROS generation rate), with the UV irradiation control value set at 100.

[0055] The results of Test Example 2 are shown in Table 4. [Table 4] JPEG2026012845000004.jpg72100

[0056] As shown in Table 5, we first confirmed that UV-B irradiation induces the generation of ROS (reactive oxygen species) in epidermal cells. Furthermore, we confirmed that Compositions 1 and 4 according to the present invention have the effect of significantly suppressing the generation of intracellular ROS (reactive oxygen species) induced by UV-B. This effect suggests that they have the effect of suppressing pigmentation and inflammation by suppressing substances induced by ROS (reactive oxygen species) that stimulate melanocytes and inflammatory substances.

[0057] Test Example 3: Evaluation test of the effect of inhibiting tyrosinase activity in human melanocytes [Process 1] Normal human epidermal keratinocytes (NHEK) were cultured at 8 × 10 4The cells were prepared at a concentration of 100 μL / mL, and 100 μL of each was seeded onto a 96-well microplate. The cells were cultured at 37°C under 5% CO2 and saturated water vapor. After 24 hours, a culture medium containing compositions 1 and 4 according to the present invention (containing ascorbic acid glucoside as an ascorbic acid derivative) was added as a sample solution, and the cells were cultured. After 24 hours, a UV-B lamp (TL20W / 12RS, manufactured by Philips) was used to irradiate the cells from the bottom of the incubator with approximately 50 mJ / cm2. 2 The culture supernatant of epidermal keratinocytes (NHEK) cultured for one day after UV irradiation was collected. In addition, a control group [UV(+)] was set up in which a culture medium containing the same concentration of PBS(-) was added to the medium instead of the sample solution and UV irradiation was performed, and a control group [UV(-)] was set up in which a culture medium containing the same concentration of PBS(-) was added to the medium instead of the sample solution and UV irradiation was not performed. The same procedures as in the test group were carried out, and the culture supernatant of each group was collected. [Process 2] Next, normal human melanocytes (NHEM) were seeded and cultured in a dedicated medium. The next day, the culture supernatant of the epidermal cells (NHEK) collected in step 1 was added to the medium as a sample solution. After culturing for another 3 days, the cells were disrupted, and L-Dopa solution (Nacalai Tesque) was added. After culturing for a certain period of time, the absorbance at 492 nm was measured to determine the intracellular tyrosinase activity. The results of Test Example 3 are shown in Table 5. [Table 5] JPEG2026012845000005.jpg76100

[0058] As shown in Table 5, we first confirmed that adding the culture supernatant of UV-irradiated epidermal cells to the culture medium of melanocytes significantly promoted tyrosinase activity. On the other hand, when epidermal cells were cultured with the addition of Compositions 1 and 4 of the present invention, adding the UV-irradiated culture supernatant to the culture medium of melanocytes also significantly suppressed tyrosinase activity. This suggests that Compositions 1 and 4 of the present invention also suppress the secretion of stimulatory factors from epidermal cells to melanocytes in response to UV irradiation, thereby preventing or ameliorating pigmentation.

[0059] In the above Test Examples 2 and 3, the extracts according to Production Examples 1 and 2 of the present invention and an ascorbic acid derivative (ascorbic acid glucoside) were evaluated. However, the present invention is not limited to this. Instead of ascorbic acid glucoside, other ascorbic acid derivatives such as magnesium L-ascorbic acid 2-phosphate, 3-O-ethyl ascorbic acid, and isostearyl ascorbyl phosphate can also be combined with the extract according to the present invention to be expected to have the effect of suppressing the secretion of stimulatory factors from epidermal cells to melanocytes.

[0060] Test Example 4: Evaluation of tyrosinase activity in human melanocytes [Process 1] A three-dimensional human skin model (LabCyte EPI-MODEL 24, manufactured by Japan Tissue Engineering Co., Ltd.) was pre-incubated (37°C, 5% CO2) according to the protocol. A test group was set up in which the extract of Production Example 1 (final concentration as a solution: 2%) and tranexamic acid (2%) were added as sample solutions, and 50 μL of each was added to the stratum corneum of the three-dimensional human skin model. The company's proprietary assay medium was used as the medium. After 6 hours of incubation, the sample solution was removed, and UV-B (60 mJ / cm2) was applied from the stratum corneum side. 2 ) was irradiated. After UV-B irradiation, the above sample solution was again added to the stratum corneum and cultured. The same procedure was repeated the next day, and the medium was collected after another 24 hours of culture. In addition, a control group [UV(+)] was set up in which 1,3 butylene glycol solution of the same concentration was added instead of the sample solution and UV irradiation was performed, and a control group [UV(-)] was set up in which 1,3 butylene glycol solution of the same concentration was added instead of the sample solution and no UV irradiation was performed, and the same procedure as in the test group was performed. [Process 2] Next, human normal melanocytes (NHEM) were cultured in a 96-well plate at 1 × 10 cells per well using the dedicated medium DermaLife M (LIFELINE CELL TECHNOLOGY, USA). 4Cells were seeded at 1000 cells / well and cultured for 24 hours at 37°C in 5% CO2. The medium collected in step 1 and the extract according to Preparation Example 2 of the present invention were added to the NHEM culture system as sample solutions. After the addition of the sample solution, normal human melanocytes (NHEM) were cultured for 2 days, and tyrosinase activity was measured. Specifically, the culture supernatant was removed, the normal human melanocytes (NHEM) were washed with PBS(-), and the cells were lysed using 1% Triton X-100 (Nacalai Tesque, Inc.) to obtain a crude enzyme solution. L-Dopa (Nacalai Tesque, Inc.) was added as a substrate, and tyrosinase activity was detected by measuring the absorbance at 492 nm. Similarly, the procedure in step 2 was performed using the medium collected from the control [UV(+)] and control [UV(-)] groups. The test results for tyrosinase activity were expressed as a relative value, with the value for the control [UV(+)] group set at 100.

[0061] The results of Test Example 4 are shown in Table 6. [Table 6] JPEG2026012845000006.jpg6199

[0062] As shown in Table 6, we first confirmed that adding the medium from the UV-irradiated three-dimensional human skin model to the culture medium for normal human melanocytes significantly promoted tyrosinase activity. Meanwhile, in the test groups containing the extracts from Preparation Example 1 and Preparation Example 2 of the present invention and tranexamic acid, we confirmed that adding the medium from the UV-irradiated three-dimensional human skin model to the culture medium for melanocytes significantly suppressed tyrosinase activity. This suggests that the combination of the extracts from Preparation Example 1 and Preparation Example 2 of the present invention and tranexamic acid (Composition 5) suppresses the secretion of stimulatory factors from epidermal tissue to melanocytes in response to UV irradiation, thereby preventing or ameliorating pigmentation such as age spots.

[0063] The following formulation examples of topical skin preparations containing the extract of the present invention, such as lotions, emulsions, and creams, are shown below, but the present invention is not limited thereto. Furthermore, by incorporating the extract into topical skin preparations containing one or more of niacinamide, vitamin E or its derivatives, and D-pantothenyl alcohol as active ingredients, the formulation examples can be expected to improve stability and also to have synergistic effects such as inhibiting aging phenomena and preventing or improving pigmentation.

[0064] Prescription example 1. Lotion [Ingredients] Part Jojoba oil 1.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 1,3-butylene glycol 1.0 Glycerin 5.0 Propanediol 3.0 Potassium hydroxide (appropriate amount) Purified water (enough to make the total volume 100 parts)

[0065] Prescription example 2: Lotion [Ingredients] Part Squalane 1.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Dipotassium glycyrrhizinate 0.1 1,3-butylene glycol 1.0 Glycerin 1.0 Pentanediol 2.0 Potassium hydroxide (appropriate amount) Purified water (enough to make the total volume 100 parts)

[0066] Prescription example 3: Lotion [Ingredients] Part Squalane 1.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Dipotassium glycyrrhizinate 0.1 Niacinamide 5.0 Tranexamic acid 2.0 1,3-butylene glycol 1.0 Glycerin 1.0 Pentanediol 2.0 Sodium pyrosulfite 0.5 Potassium hydroxide (appropriate amount) Purified water (enough to make the total volume 100 parts) A lotion containing niacinamide and tranexamic acid as active ingredients was obtained that suppressed crystal precipitation and color change and improved stability.

[0067] Prescription example 4: Lotion [Ingredients] Part Squalane 1.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Niacinamide 5.0 1,3-butylene glycol 1.0 Glycerin 5.0 Hydrolyzed Collagen 0.1 Pentanediol 1.0 Sodium citrate (appropriate amount) Purified water (enough to make the total volume 100 parts) A lotion containing niacinamide as an active ingredient was obtained that suppressed crystal precipitation and color change and improved stability.

[0068] Prescription example 5. Lotion [Ingredients] Part Hydrogenated castor oil 1.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Glycerin 5.0 Tranexamic acid 1.0 Tocopheryl acetate 0.3 Water-soluble collagen 0.01 1,3-butylene glycol 1.0 Pentanediol 2.0 Sodium pyrosulfite 0.5 Potassium hydroxide (appropriate amount) Purified water (enough to make the total volume 100 parts) A lotion containing tranexamic acid as an active ingredient was obtained that suppressed crystal precipitation and color change and improved stability.

[0069] Prescription example 6. Lotion [Ingredients] Part Hydrogenated castor oil 1.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Glycerin 5.0 Niacinamide 5.0 Ascorbic Acid Glucoside 2.0 Tocopheryl acetate 0.3 Water-soluble collagen 0.01 1,3-butylene glycol 1.0 Pentanediol 2.0 Potassium hydroxide (appropriate amount) Purified water (enough to make the total volume 100 parts) A lotion containing niacinamide and ascorbic acid glucoside as active ingredients was obtained that suppressed crystal precipitation and color change and improved stability.

[0070] Prescription example 7. Lotion A lotion was obtained by compounding 3.0 parts of 3-O-ethyl ascorbic acid in place of ascorbic acid glucoside in the composition of Formulation Example 6.

[0071] Prescription example 8. Lotion A lotion was obtained by compounding 3.0 parts of L-ascorbic acid 2-phosphate magnesium ester in place of ascorbic acid glucoside in the composition of Formulation Example 6.

[0072] Prescription example 9. Emulsion [Ingredients] Part Squalane 5.0 Jojoba oil 1.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Polyoxyethylene (20) Sorbitan Monostearate 1.0 Lipophilic glyceryl stearate 1.0 Hydrogenated soy lecithin 1.5 Dipotassium glycyrrhizinate 0.1 Lactic acid bacteria fermented rice 2.0 Maltitol 0.1 Arginine 0.01 Glycerin 3.0 Carboxymethylcellulose 0.3 Xanthan gum 0.2 Sodium hyaluronate 0.01 1,3-butylene glycol 0.1 Phenoxyethanol 0.5 Pentylene glycol 0.5 Diglycerin 0.3 Purified water (enough to make the total volume 100 parts)

[0073] Prescription example 10. Emulsion An emulsion was obtained by compounding 0.1 parts of stearyl glycyrrhetinate in place of dipotassium glycyrrhizinate in the composition of Formulation Example 9.

[0074] Prescription example 11. Emulsion [Ingredients] Part Squalane 5.0 Jojoba oil 1.0 Polyoxyethylene (20) Sorbitan Monostearate 1.0 Lipophilic glyceryl stearate 1.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Niacinamide 5.0 D-Pantothenyl alcohol 0.3 Tranexamic acid 2.0 Hydrogenated soy lecithin 1.5 Lactic acid bacteria fermented rice 2.0 Maltitol 0.1 Arginine 0.01 Glycerin 3.0 Carboxymethylcellulose 0.3 Xanthan gum 0.2 Sodium hyaluronate 0.01 1,3-butylene glycol 0.1 Phenoxyethanol 0.5 Pentylene glycol 0.5 Diglycerin 0.3 Sodium pyrosulfite 0.2 Purified water (enough to make the total volume 100 parts) A lotion containing niacinamide, D-pantothenyl alcohol, and tranexamic acid as active ingredients was obtained that suppressed crystal precipitation and color change and improved stability.

[0075] Prescription example 12. Emulsion [Ingredients] Part Squalane 5.0 Jojoba oil 1.0 Polyoxyethylene (20) Sorbitan Monostearate 1.0 Lipophilic glyceryl stearate 1.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Niacinamide 5.0 D-Pantothenyl alcohol 0.1 Tranexamic acid 1.0 Dipotassium glycyrrhizinate 0.08 Hydrogenated soy lecithin 1.5 Lactic acid bacteria fermented rice 2.0 Maltitol 0.1 Arginine 0.01 Glycerin 3.0 Carboxymethylcellulose 0.3 Xanthan gum 0.2 Sodium hyaluronate 0.01 1,3-butylene glycol 0.1 Phenoxyethanol 0.5 Pentylene glycol 0.5 Diglycerin 0.3 Sodium pyrosulfite 0.2 Purified water (enough to make the total volume 100 parts)

[0076] Prescription example 13. Emulsion An emulsion was obtained by compounding 0.1 parts of stearyl glycyrrhetinate in place of dipotassium glycyrrhizinate in the composition of Formulation Example 12.

[0077] Prescription example 14. Emulsion [Ingredients] Part Squalane 5.0 Castor oil 1.0 Lipophilic glyceryl stearate 1.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Dipotassium glycyrrhizinate 0.07 Niacinamide 5.0 Ascorbic Acid Glucoside 2.0 Hydrogenated soy lecithin 1.5 Lactic acid bacteria fermented rice 2.0 Maltitol 0.1 Arginine 0.01 Glycerin 3.0 Carboxymethylcellulose 0.3 Sodium hyaluronate 0.01 Hydrolyzed Hyaluronic Acid 0.01 1,3-butylene glycol 0.1 Phenoxyethanol 0.5 Pentylene glycol 0.5 Diglycerin 0.3 Potassium hydroxide (appropriate amount) Purified water (enough to make the total volume 100 parts) A lotion containing niacinamide and ascorbic acid glucoside as active ingredients was obtained that suppressed crystal precipitation and color change and improved stability.

[0078] Prescription example 15. Wrinkle improvement cream [Ingredients] Part Olive oil 5.0 Jojoba oil 5.0 Squalane 5.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Niacinamide 5.0 Tranexamic acid 2.0 Dipotassium glycyrrhizinate 0.06 Lactic acid bacteria fermented rice 2.0 Maltitol 0.1 Arginine 0.01 Hydrogenated lecithin 0.5 Carboxyvinyl polymer 0.3 Water-soluble collagen 0.1 1,3-butylene glycol 0.1 Phenoxyethanol 0.5 Pentylene glycol 0.5 Diglycerin 0.3 Purified water (enough to make the total volume 100 parts) A lotion containing niacinamide and tranexamic acid as active ingredients was obtained that suppressed crystal precipitation and color change and improved stability.

[0079] Prescription example 16. Emulsion An emulsion was obtained by compounding 0.1 part of stearyl glycyrrhetinate in place of 0.06 part of dipotassium glycyrrhizinate in Formulation Example 15.

[0080] Prescription example 17. Facial cleanser [Ingredients] Part Glyceryl Stearate 2.5 Squalane 3.0 Glycerin 3.0 Polyglyceryl-10 Laurate 3.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Dipotassium glycyrrhizinate 0.1 Water-soluble collagen 0.01 Sodium hyaluronate 0.01 Isopropylmethylphenol 0.1 1,3-butylene glycol 2.0 Purified water (enough to make the total volume 100 parts)

[0081] Prescription example 18. 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 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Dipotassium glycyrrhizinate 0.1 Salicylic acid 0.1 Sodium salicylate 0.1 Tocopheryl acetate 0.1 Pyrithione Zinc 0.3 Benzoic acid 0.2 Triclosan 0.2 Citric acid 0.1 Propylene Glycol 2.0 Purified water (enough to make the total volume 100 parts)

[0082] Prescription example 19. 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 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Dipotassium glycyrrhizinate 0.03 β-Glycyrrhetinic acid 0.03 Stearyl glycyrrhetinate 0.03 Allantoin 0.1 Isopropylmethylphenol 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)

[0083] Formulation example 20. Cleansing cosmetics [Ingredients] Part Potassium cocoyl glycinate 5.0 Glycerin 10.0 Glyceryl Caprylate 1.0 Sodium lauroyl aspartate 10.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Monoammonium glycyrrhizinate 0.03 β-Glycyrrhetinic acid 0.03 Stearyl glycyrrhetinate 0.03 Niacinamide 1.0 Cetyl alcohol 3.0 Myristyl Alcohol 3.0 Isopropyl methyl alcohol 0.1 Allantoin 0.1 Sulfur 0.5 Tocopheryl acetate 0.1 Triclosan 0.1 Trichlorocarbanide 0.5 Trichlorohydroxydiphenyl ether 0.2 Concentrated Benzalkonium Chloride Solution 50 0.2 Benzalkonium chloride 0.1 Purified water (enough to make the total volume 100 parts)

[0084] Prescription example 21. Sheet mask A sheet mask is obtained by impregnating a nonwoven fabric with the following ingredients. [Ingredients] Part Glycerin 3.0 Methylparaben 0.2 Citric acid 0.1 Sodium citrate 0.3 Xanthan gum 1.0 Water-soluble collagen 1.0 Sodium hyaluronate 1.0 Extract of Preparation Example 1 2.0 Extract of Preparation Example 2 2.0 Dipotassium glycyrrhetinate 0.06 Niacinamide 5.0 Tranexamic acid 2.0 1,3-butylene glycol 2.0 Hexanediol 0.1 Potassium hydroxide (appropriate amount) Purified water (enough to make the total volume 100 parts)

Claims

1. A topical skin preparation containing an extract of gentian of the genus Gentiana of the family Gentianaceae and an extract of Bletilla striata of the genus Orchidaceae as active ingredients.

2. 2. The external skin preparation according to claim 1, further comprising one or more of glycyrrhizinic acid or a derivative thereof, glycyrrhetinic acid or a derivative thereof, tranexamic acid or a derivative thereof, and ascorbic acid or a derivative thereof.

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