Vitamin d metabolism promoter

Abstract

To provide an active ingredient which is derived from a natural product, is excellent in biological safety, promotes the metabolism of vitamin D in the epidermis, and promotes the vitamin D to more effectively exhibit its function.SOLUTION: An extract of Liliumconcolor or its sub-species is used as an active ingredient.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an agent that promotes vitamin D metabolism in the epidermis and stimulates the differentiation of epidermal cells. [Background technology]

[0002] Vitamin D, an essential component for the body, is broadly divided into two forms: vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D3 is known to be orally ingested from food and produced in skin exposed to sunlight, and is therefore used as an ingredient in dietary supplements.

[0003] However, it is known that most vitamin D3 used in nutritional supplements is in an inactive form. It has been revealed that this inactive vitamin D3 (cholecalciferol) is hydroxylated in the liver or elsewhere in the body and converted to calcifediol or calcitriol, thereby becoming physiologically active (Non-Patent Document 1). Therefore, there has been a need for a technology to more efficiently convert this vitamin D3 into an active form that is physiologically active in the body. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Toshiyuki Sakaki, Vitamins (Japan), 93 (11), 469-477 (2019) DISCLOSURE OF THE INVENTION [Problem to be solved by the invention]

[0005] In view of the above problems of the prior art, the present inventors have conducted extensive research and found that an extract of Lilium caryophyllus or its subspecies has the effect of activating enzymes (CYP2R1, CYP27B1, CYP27A1) that convert vitamin D3 into its active form, the effect of promoting vitamin D metabolism in the epidermis, and the effect of promoting epidermal cell differentiation. [Means for solving the problem]

[0006] The present invention is a vitamin D metabolism promoter containing an extract of Lilium concolor or a subspecies thereof as an active ingredient. The present invention relates to an epidermal cell differentiation promoter containing an extract of Lilium concolor or a subspecies thereof as an active ingredient. [Effects of the Invention]

[0007] The present invention promotes vitamin D metabolism in the epidermis by applying to the skin a preparation containing an extract of Lilium concolor or its subspecies as an active ingredient. As a result, vitamin D can be more efficiently utilized in the epidermis. Furthermore, the present invention suggests that promoting vitamin D metabolism in the epidermis promotes epidermal cell differentiation, promoting, for example, the formation of the cornified envelope of the stratum corneum (expression of involucrin, transglutaminase, etc.), NMF synthesis (expression of peptidylarginine deiminases), the secretion of antimicrobial peptides, and the expression of stratum corneum desquamating enzymes (expression of kallikreins, etc.). Therefore, the present invention is expected to maintain a strong barrier function while regulating cell turnover and promoting stratum corneum desquamation, which restores the epidermis to a normal state. DETAILED DESCRIPTION OF THE INVENTION

[0008] The present invention relates to a plant extract containing, as an active ingredient, an extract of Lilium concolor or a subspecies thereof, which belongs to the genus Lilium and belongs to the family Liliaceae. Examples of subspecies of Lilium include Lilium concolor Salisb. var. mutsuanum Makino, Lilium concolor var. pulchellum, Lilium concolor f. coridion, and Lilium concolor var.

[0009] The parts of the lily of the valley that can be extracted in the present invention include the whole plant, leaves, stems, roots, flowers, buds, and new shoots.

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

[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, as well as skin irritation, and because they can be widely applied to external skin preparations (cosmetics, quasi-drugs, external pharmaceuticals, etc.). Preferred examples of hydrophilic solvents include the use of water, lower alcohols (particularly ethanol), or polyhydric alcohols (particularly 1,3-butylene glycol and glycerin) 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 and glycerin).

[0013] When a mixed solvent is used, the mixing ratio, for example, of water and a lower alcohol or a polyhydric alcohol, is preferably 1:5 to 25:1 in volume ratio (the same applies hereinafter).

[0014] When preparing the extract, the pH is not particularly limited, but is generally preferably in the range of 3 to 9. In this sense, if necessary, the extraction solvent may be blended with an alkalinity adjuster such as sodium hydroxide, sodium carbonate, or potassium hydroxide, or an acidity adjuster such as citric acid, hydrochloric acid, phosphoric acid, or sulfuric acid to adjust the pH to the desired level.

[0015] 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 alone or a mixture of water and a lower alcohol or a polyhydric alcohol is used as the solvent, the extraction temperature is preferably in the range of 0°C to 80°C, and the extraction time is preferably in the range of 1 to 168 hours (1 hour to 1 week), more preferably 1 to 120 hours (1 hour to 5 days).

[0016] In order to remove impurities and improve stability, the extract of the present invention may be subjected to one or a combination of two or more of activated carbon treatment, ion exchange resin treatment, synthetic adsorbent treatment, silica gel treatment, and recrystallization treatment to remove impurities other than the active ingredients.

[0017] The extract prepared as described above may be used as an ingredient in a composition for external use on the skin as is after adjusting the pH to 3 to 8, or may be used at a desired concentration by concentrating under reduced pressure, etc. The extract may also be dried by a conventional method such as spray drying.

[0018] Furthermore, the extract of the present invention can be incorporated into topical skin preparations (cosmetics, quasi-drugs, topical pharmaceuticals), and examples of such preparations include, but are not limited to, emulsions, creams, lotions, essences, packs, lipsticks, foundations, sheet masks, liquid foundations, makeup press powders, blushers, face powders, facial cleansers, body shampoos, cleansing cosmetics such as soaps, hair growth products, and even bath additives.

[0019] When the extracts of the present invention are incorporated into a composition, the amount of each extract added is generally in the range of 0.00001 to 5.0% by weight in terms of solid content.

[0020] When the extract of the present invention is incorporated into topical skin preparations (cosmetics, quasi-drugs, topical pharmaceuticals, etc.), ingredients used in the composition, such as oily ingredients, surfactants (synthetic and natural), moisturizers, thickeners, emulsifiers or emulsifying aids, preservatives / bactericides, powder ingredients, UV absorbers, antioxidants, sequestering agents, pigments, fragrances, anti-wrinkle agents, anti-pigmentation agents, and other physiologically active ingredients, can be appropriately incorporated as needed.

[0021] 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, and paraffin wax. 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; 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).

[0022] 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.

[0023] Examples of emulsifiers and 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.

[0024] 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, and various amino acids and their derivatives.

[0025] 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, pullulan, and aloe polysaccharides; 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.

[0026] Examples of 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.

[0027] 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 ammonium 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.

[0028] Examples of cell activators include pantothenyl alcohol, menthol, dl-menthol, and γ-oryzanol.

[0029] Anti-acne agents include, for example, sulfur, salicylic acid or its salts, photosensitizer No. 201, pyridoxine dicaprylate, and the like.

[0030] 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.

[0031] 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.

[0032] 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.

[0033] Examples of sequestering agents include disodium edetate, trisodium edetate, tetrasodium edetate, etidronic acid or a salt thereof (such as tetrasodium etidronate), gluconic acid or a salt thereof (such as sodium gluconate), diethylenetriaminepentaacetic acid or a salt thereof (such as pentasodium diethylenetriaminepentaacetate), hydroxyethanediphosphonic acid or a salt thereof (such as tetrasodium hydroxyethanediphosphonate), and phytic acid or a salt thereof (such as sodium phytate).

[0034] Examples of anti-pigmentation agents include one or more selected from kojic acid or its derivatives, ascorbic acid or its derivatives, hydroquinone or its derivatives, ellagic acid and its derivatives, resorcinol derivatives, 4-methoxysalicylic acid potassium salt, vitamin E or its derivatives, nicotinic acid or its derivatives, magnolignan (5,5'-dipropyl-biphenyl-2,2'-diol), hydroxybenzoic acid and its derivatives, vitamin E and its derivatives, α-hydroxy acid, AMP (adenosine monophosphate, adenosine monophosphate), placenta extract, and linoleic acid.

[0035] Examples of the 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 the ascorbic acid derivatives include sodium L-ascorbic acid 2-phosphate, magnesium L-ascorbic acid 2-phosphate, sodium L-ascorbic acid 2-sulfate, and L-ascorbic acid 2-sulfate. ascorbic acid ester salts such as ammonium magnesium, ascorbic acid sugar derivatives such as L-ascorbic acid-2-glucoside (2-O-α-D-glucopyranosyl-L-ascorbic acid) and L-ascorbic acid-5-glucoside (5-O-α-D-glucopyranosyl-L-ascorbic acid), 6-acylated products of these ascorbic acid sugar derivatives (the acyl group is a hexanoyl group, an octanoyl group, a decanoyl group, etc.), L-ascorbic acid tetraisopalmitate, ... Examples of the hydroquinone derivatives include arbutin (hydroquinone-β-D-glucopyranoside) and α-arbutin (hydroquinone-α-D-glucopyranoside). Examples of the 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. Examples of nicotinic acid derivatives include nicotinamide and benzyl nicotinate. Examples of vitamin E derivatives include vitamin E nicotinate and vitamin E linoleate. Examples of α-hydroxy acids include lactic acid, malic acid, succinic acid, citric acid, and α-hydroxyoctanoic acid.

[0036] Examples of anti-wrinkle agents include vitamin A or its derivatives, 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, and niacinamide.

[0037] Furthermore, it is also possible to use in combination components derived from natural products such as the following plants or microorganisms: collagen or hydrolysates thereof, yeast extracts or hydrolysates, lactic acid bacteria cultures, 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, Nelumbosacaceae plants, Cucurbitaceae plants, Araliaceae plants, Solanaceae plants, Bignoniaceae plants, Actinidiaceae plants, Mulberry plants, Iridaceae plants, Campanulaceae plants, Oleaceae plants, Actinidiaceae plants, Mulberry plants, Rhamnaceae plants, Orchidaceae plants, and Anacardiaceae plants. Examples of suitable extracts include extracts of one or more plants selected from the family Garcinia, Valenciaceae, Rutaceae, Myrtaceae, Liliaceae, Crassulaceae, Cupressaceae, Convolvulaceae, and Asparagaceae, or hydrolysates or fermented products thereof; extracts of one or more seaweeds 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.

[0038] 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, and bamboo shoot skin extract from Madake or Moso bamboo. Furthermore, as ingredients derived from Brassicaceae plants, white mustard extract or its hydrolysate, and white mustard fermentation product are preferred. 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-scented black tea, etc.). As ingredients derived from Rosaceae plants, preferred are Damask rose flower extract, peach flower, leaf, or immature fruit extract, strawberry flower extract, cherry blossom flower or leaf extract, and apricot fruit or seed 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 globulus 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 oranges, bergamot fruit extracts, grapefruit or banpeiyu fruit (including immature fruits), extracts containing flavonoids and their glycosides contained in plants such as grapefruit or hassaku, or Japanese pepper seed extract are preferred. As a component derived from a plant of the Liliaceae family, an extract of daylily, daylily, Casablanca lily, Madonna lily, or Japanese lily is preferred. As a component derived from a plant of the Crassulaceae family, an extract or fermented product of Rhodiola rosea 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 striata 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 preferred. As a component derived from a plant of the Asparagaceae family, an extract of asparagus is particularly preferred. As a component derived from seaweed of the Laminariaceae family, kelp extract is particularly preferred, as a component derived from seaweed of the Mirinaceae family, katamen kyrinsai extract is particularly preferred, as a component derived from seaweed of the Ulva family, Ulva pertusa extract is particularly preferred, and as a component derived from seaweed of the Funoriaceae family, funori extract is particularly preferred.

[0039] 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.

[0040] Preparation Example 1. Preparation of extract (1) A mixed solvent of 500 g of purified water and 500 g of 1,3-butylene glycol was added to 1.0 g of dried leaves and stems of Lilium tricolor (Lilium genus, Liliaceae), and the mixture was stirred at 80°C for 4 hours. The crude extract was then filtered to obtain 610 g of a pale yellow extract (solid concentration: 0.10%).

[0041] Preparation Example 2. Preparation of extract (2) 1000 g of purified water was added to 1.0 g of dried leaves and stems of Lilium tricolor (Lilium genus, Liliaceae), and the mixture was stirred at 80°C for 4 hours. The crude extract was then filtered to obtain 600 g of a pale yellow extract (solid concentration: 0.08%).

[0042] Preparation Example 3. Preparation of extract (3) The same procedure as in Production Example 1 was carried out, except that flowers were used instead of the leaves and stems of Lilium thunbergii in Production Example 1, to obtain a pale yellow extract (solid concentration: 0.11%).

[0043] Preparation Example 4. Preparation of extract (4) The same procedure as in Production Example 1 was carried out, except that the leaves and stems of Lilium gracilis were used instead of Lilium cristatum in Production Example 1, to obtain a pale yellow extract (solid concentration: 0.09%).

[0044] Test Example 1. Evaluation of gene expression in epidermal keratinocytes Normal epidermal cells (NHEK) were seeded onto a 24-well plate (1 × 10 5The cells were cultured in a 5% CO2, saturated steam atmosphere at 37°C (100 cells / well). After 24 hours, the extract from Preparation Example 1 was added as a sample solution, and the epidermal keratinocytes were cultured under the same conditions. The sample solution was added so that the final concentration of the solution in the culture medium was 2.0%. A control group was also cultured with the same concentration of 30% butylene glycol (hereinafter referred to as "30% BG") instead of the sample solution. After 48 hours of culture, the cells from each test group were harvested with 0.5 mL of ISOGEN II reagent (Nippon Gene Co., Ltd.), and total RNA was purified according to standard methods. cDNA was synthesized by reverse transcription using a designated kit (PrimeScript RT reagent Kit with gDNA Eraser (Perfect Real Time) (Takara Bio Inc.)). Using the synthesized cDNA as a sample, the expression of various genes and the expression of the internal standard G3PDH 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.). The test results were obtained by comparing the expression levels of each gene in each test group when the expression level of the G3PDH 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 expression level of that gene in other test groups was calculated. In this test example, the genes encoding enzymes that convert vitamin D3 to its active form (CYP2R1, CYP27B1, CYP27A1) were focused on and their expression rates were evaluated.

[0045] The results of Test Example 1 are shown in Table 1. [Table 1] JPEG2026014469000001.jpg40117

[0046] As shown in Table 1, it was confirmed that the extract of the present invention significantly enhances the expression of genes encoding enzymes (CYP2R1, CYP27B1, CYP27A1) that convert vitamin D3 to its active form. Thus, according to the present invention, vitamin D metabolism can be promoted by converting vitamin D to its active form in the epidermis, thereby promoting the more effective function of vitamin D in the epidermis. Furthermore, since vitamin D is required for the differentiation of epidermal keratinocytes, it is suggested that it contributes to maintaining the homeostasis of the epidermal layer of the skin.

[0047] Test Example 2: Evaluation of transcriptional activity of vitamin D receptor Normal human epidermal cells were grown in HuMedia-KG2 (Kurabo) containing a growth additive at a concentration of 1 × 10 5The cells were prepared at a concentration of 100 μL / mL, and 100 μL was seeded into a 96-well microplate and cultured at 37°C under 5% CO2 and saturated steam. After 24 hours of culture, the medium was replaced with HuMedia-KB2 (Kurabo). A firefly luciferase reporter vector containing a vitamin D receptor-binding sequence (VDRE) and a vector containing Renilla luciferase as an internal standard (Cignal HIF Pathway Reporter Assay Kit) (QIAGEN) were then transfected into the cells using ViaFect transfection reagent (Promega). After 24 hours, the extract from Preparation Example 1 was added as a sample solution, and epidermal keratinocytes were cultured under the same conditions. The sample solution was added to the culture medium to achieve final concentrations of 0.5%, 1.0%, and 2.0%. A control group was prepared by adding 30% BG solution at the same concentration instead of the sample solution. After further incubation under the same conditions for 24 hours, cholecalciferol (prepared in HuMedia-KB2) was added to a final concentration of 100 nM. After 24 hours, the cell contents were extracted, and luciferase activity in the cell extract was measured using a luciferase assay system (Promega) and a luminometer (Promega GloMax-Multi+Detection System). The firefly luciferase activity (RARE transcription level) was divided by the Renilla luciferase activity (cell mass) to calculate vitamin A receptor transcription activity per cell. Furthermore, the VDRE transcription activity in the control group was also tested and calculated in the same way. The VDRE transcription activity was calculated relative to the control group, with the control group set at 100.

[0048] The results of Test Example 2 are shown in Table 2. [Table 2] JPEG2026014469000002.jpg46120

[0049] As shown in Table 2, it was confirmed that the extract of the present invention significantly enhanced luciferase activity when used in combination with vitamin D (cholecalciferol) produced in the skin. In Test Example 2, the transcriptional activity of vitamin D receptor was evaluated by luciferase activity, suggesting that the extract of the present invention has the effect of increasing the transcriptional activity of vitamin D receptor by converting cholecalciferol to calcifediol or calcitriol.

[0050] The results of Test Examples 1 and 2 above suggest that the extract of the present invention can convert vitamin D produced in the epidermis by factors such as sun exposure into active vitamin D, thereby promoting vitamin D metabolism and thereby contributing to epidermal homeostasis. Furthermore, the present invention suggests that promoting vitamin D metabolism in the epidermis promotes epidermal cell differentiation, thereby promoting, for example, the formation of the cornified envelope of the stratum corneum (expression of involucrin, transglutaminase, etc.), NMF synthesis (expression of peptidylarginine deiminases), the secretion of antimicrobial peptides, and the expression of stratum corneum desquamating enzymes (expression of kallikreins, etc.). Therefore, the present invention is expected to maintain a strong barrier function while regulating cell turnover and promoting stratum corneum desquamation, which restores the epidermis to a normal state.

[0051] Prescription example 1. Lotion [Ingredients] Part Extract of Preparation Example 1 0.5 Squalane 0.2 Polyoxyethylene (5.5) Cetyl Alcohol 5.0 Tocopherol acetate 0.02 Dipotassium glycyrrhizinate 0.5 Nicotinamide 0.1 1,3-butylene glycol 5.0 Sodium citrate 0.2 Methylparaben 0.1 Purified water (enough to make the total volume 100 parts)

[0052] Prescription example 2: Lotion A lotion was obtained in the same manner as in Formulation Example 1, except that 0.5 parts of the extract from Preparation Example 2 was used in place of 0.5 parts of the extract from Preparation Example 1.

[0053] Prescription example 3: Lotion A lotion was obtained in the same manner as in Formulation Example 1, except that 0.5 parts of the extract from Preparation Example 3 was used in place of 0.5 parts of the extract from Preparation Example 1.

[0054] Prescription example 4: Lotion A lotion was obtained in the same manner as in Formulation Example 1, except that 0.5 parts of the extract from Preparation Example 4 was used in place of 0.5 parts of the extract from Preparation Example 1.

[0055] Prescription example 5. Lotion [Ingredients] Part Extract of Preparation Example 1 1.0 Glyceryl Caprylate 3.0 Polyglyceryl-10 Laurate 3.0 Cetyl alcohol 2.0 Behenyl Alcohol 2.0 Niacinamide 5.0 Dipotassium glycyrrhizinate 0.1 Stearyl Glycyrrhetinate 0.1 Glycerin 1.0 1,3-butylene glycol 1.0 Pentanediol 1.0 Potassium hydroxide 0.5 Purified water (enough to make the total volume 100 parts)

[0056] Prescription example 6. Lotion [Ingredients] Part Extract of Preparation Example 2 1.0 Jojoba oil 1.0 Polyoxyethylene (5.5) Cetyl Alcohol 5.0 Methylparaben 0.1 Ascorbic Acid Glucoside 2.0 Niacinamide 3.5 Tranexamic acid 2.0 Glycerin 5.0 1,3-butylene glycol 5.0 Sodium citrate 0.2 Sodium metabisulfite 0.2 Purified water (enough to make the total volume 100 parts)

[0057] Prescription example 7. Emulsion [Ingredients] Part Extract of Preparation Example 1 2.0 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 Ascorbic acid phosphate magnesium salt 3.0 Arbutin 3.0 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 Dipotassium glycyrrhizinate 0.1 Stearyl Glycyrrhetinate 0.1 Isopropylmethylphenol 0.1 Water-soluble collagen 1.0 Hydrolyzed Collagen 1.0 Acetyl hyaluronic acid 0.1 Disodium edetate 0.05 Diethylenetriaminepentaacetic acid pentasodium 0.05 Potassium hydroxide (appropriate amount) Purified water (enough to make the total volume 100 parts)

[0058] Prescription example 8. Emulsion An emulsion was obtained in the same manner as in Formulation Example 7, 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.

[0059] Prescription example 9. Emulsion An emulsion was obtained in the same manner as in Formulation Example 7, except that 2.0 parts of ascorbyl tetrahexyldecanoate was used in place of 2.0 parts of magnesium ascorbyl phosphate.

[0060] Prescription example 10. Emulsion An emulsion was obtained in the same manner as in Formulation Example 7, except that 2.0 parts of ascorbic acid phosphate magnesium salt was replaced with 3.0 parts of 3-O-ethyl ascorbic acid.

[0061] Prescription example 11. Emulsion An emulsion was obtained in the same manner as in Formulation Example 7, except that 2.0 parts of ascorbic acid phosphate magnesium salt and 4.0 parts of niacinamide were used in place of potassium hydroxide.

[0062] Prescription example 12. Cream [Ingredients] Part Extract of Preparation Example 1 2.0 Olive oil 5.0 Squalane 5.0 Jojoba oil 5.0 Jojoba Wax 1.0 Behenyl Alcohol 1.0 Stearyl Alcohol 1.0 Candelilla Wax 1.0 Lactic acid bacteria fermented rice 2.0 Soybean-derived hydrogenated lecithin 0.5 Carboxyvinyl Polymer 1.0 Sodium alginate 1.0 Glycerin 2.0 Pentanediol 1.0 pH adjuster (appropriate amount) Purified water (enough to make the total volume 100 parts)

[0063] Prescription example 13. Cream [Ingredients] Part Extract of Preparation Example 2 1.0 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 Niacinamide 5.0 Lactic acid bacteria fermented rice 2.0 Hydrogenated lecithin 0.5 Hydrogenated lysolecithin 0.5 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)

[0064] Example 14. Pack [Ingredients] Part Extract of Preparation Example 1 1.0 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 Water-soluble collagen 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)

[0065] Prescription example 15. Hair shampoo [Ingredients] Part Extract of Preparation Example 1 2.0 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 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 Purified water (enough to make the total volume 100 parts)

[0066] Prescription example 16. Hair conditioner [Ingredients] Part Extract of Preparation Example 1 1.0 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 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)

[0067] Formulation example 17. Cleansing cosmetics [Ingredients] Part Extract of Preparation Example 1 2.0 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 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 Purified water (enough to make the total volume 100 parts)

[0068] Prescription example 18. Sheet mask A sheet mask is obtained by impregnating a nonwoven fabric with the following ingredients. [Ingredients] Part Extract of Preparation Example 1 2.0 Niacinamide 1.0 Citric acid 0.1 Sodium citrate 0.3 Xanthan gum 0.1 Water-soluble collagen 0.1 Sodium hyaluronate 0.01 Glycerin 1.0 1,3-butylene glycol 2.0 Pentanediol 1.0 Potassium hydroxide (appropriate amount) Purified water (enough to make the total volume 100 parts)

[0069] Prescription example 19. Beauty serum [Ingredients] Part Extract of Preparation Example 1 2.0 Sodium hyaluronate 1.0 Water-soluble collagen 1.0 Tranexamic acid 0.1 Ethanol 2.0 Glycerin 5.0 1,3-butylene glycol 5.0 Methylparaben 0.1 Citric acid 0.3 Sodium citrate 0.6 Eucheuma muscaria extract 5.0 Purified water (enough to make the total volume 100 parts)

[0070] Prescription example 20. Cream [Ingredients] Part Extract of Preparation Example 4 2.0 Olive oil 5.0 Squalane 5.0 Jojoba oil 5.0 Jojoba Wax 1.0 Shea Butter 2.0 Behenyl Alcohol 1.0 Stearyl alcohol 1.5 Candelilla Wax 0.5 Niacinamide 1.0 Lactic acid bacteria fermented rice 3.0 Hydrogenated Lecithin 2.0 Eucheuma muscaria extract 2.0 Carboxyvinyl polymer 0.3 Sodium alginate 0.2 Glycerin 4.0 Potassium hydroxide (appropriate amount) Purified water (enough to make the total volume 100 parts)

Claims

1. A vitamin D metabolism promoter containing an extract of Lilium concolor or its subspecies as an active ingredient.

2. An epidermal cell differentiation improver containing an extract of Lilium concolor or its subspecies as an active ingredient.

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