KR20230147474A - Composition for preventing or improving skin aging or skin pigmentation comprising desmethylxanthohumol as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for preventing or improving skin aging or pigmentation containing desmethylxanthohumol as an active ingredient. The composition containing desmethylxanthohumol of the present invention as an active ingredient not only has low cytotoxicity, but also increases the expression of pro-collagen, which is reduced by ultraviolet rays, and inhibits the synthesis of melanin, thereby preventing skin aging or It is expected to be useful in preventing or improving pigmentation.

Description

Composition for preventing or improving skin aging or skin pigmentation comprising desmethylxanthohumol as an active ingredient}

The present invention relates to a composition for preventing or improving skin aging or pigmentation containing desmethylxanthohumol as an active ingredient.

Now that the human lifespan has entered the era of 100 years due to the development of medical science, people are interested in maintaining health and youth and living beautifully. In particular, skin is a body tissue that exists in the outermost layer of the human body, and is an important element that protects the body from the external environment through various physiological functions and is also responsible for externally visible aesthetic functions. As the skin ages, not only does skin immune function deteriorate, but also external deformities such as decreased skin elasticity, changes in skin color, and formation of skin wrinkles occur. This skin aging process can be classified into intrinsic aging and extrinsic aging. Intrinsic aging is natural aging that occurs naturally as we age, and is mainly influenced by genetic factors, so it is difficult to control artificially. On the other hand, extrinsic aging occurs due to an increase in free radicals in the body due to environmental factors. Relatively artificial control is possible. Therefore, research on functional cosmetic materials for preventing skin aging, focusing on extrinsic aging, is actively underway.

Collagen is a representative fibrous protein that exists throughout the body, and type 1 collagen mainly exists in the skin. Collagen is produced in skin fibroblasts and plays an important role in skin, including skin firmness, connective tissue resistance and tissue adhesion, support of cell adhesion, and induction of cell division and differentiation. Therefore, it can be seen that collagen is closely related to the formation of skin wrinkles. Collagen synthesis decreases due to age and photoaging caused by ultraviolet irradiation, which reduces skin elasticity and creates wrinkles. Therefore, in discovering new materials for preventing and treating skin aging, finding substances that promote collagen synthesis can be a good strategy. Substances that promote collagen synthesis known to date include vitamin C, retinoic acid transforming growth factor, protein derived from animal placenta, chlorella extract, and betulinic acid. However, the above substances have limitations in their use or have minimal effects due to stability issues when applied to the skin, so it is difficult to expect an effect of improving skin wrinkles by actually promoting skin collagen synthesis. Therefore, there is a need to develop a new skin aging prevention and improvement material with excellent collagen synthesis promoting ability and improved stability.

Meanwhile, many factors are involved in determining a person's skin color, including the activity of melanocytes, which produce melanin pigment; distribution of blood vessels; thickness of the skin; Factors such as the presence or absence of pigments inside and outside the human body, such as carotenoids and bilirubin, are important. Among these, the most important factor is the black pigment called melanin, which is produced by the action of various enzymes such as tyrosinase in melanocytes in the human body. Melanin protects skin organs below the dermis by blocking external ultraviolet rays, and plays a useful role in protecting proteins and genes in the skin from damage caused by free radicals generated within the skin. However, if more melanin is produced than necessary, it not only causes skin aging but also hyperpigmentation such as spots and freckles, which is not only aesthetically undesirable but can also cause skin cancer. Therefore, it can be said that it is desirable to suppress excessive melanin production not only to satisfy beauty desires, but also to maintain skin health and treat skin diseases. Methods for inhibiting melanin synthesis include preventing or reducing exposure to ultraviolet rays by using cosmetics containing an appropriate sunscreen; A method of inhibiting cell expression of melanocytes, which are melanin-synthesizing cells; There are methods to suppress melanin synthesis by suppressing the expression of tyrosinase. However, substances such as arbutin, kojic acid (5-hydroxy-2-hydormethyl-v-pyrone), and hydroquinone, which are currently being developed as tyrosinase inhibitors, have low efficacy, instability of the substance itself, and are harmful to the skin. It has problems such as toxicity. Therefore, there is a need to discover new natural substances that are non-toxic and stable on the skin and have a high melanin production inhibition effect.

Therefore, the present inventors have carefully studied compounds derived from natural substances that are non-toxic and stable on the skin and have the effect of promoting collagen synthesis and inhibiting melanin production, and as a result, the desmethylxanthohumol of the present invention has excellent effects on preventing or improving skin aging or pigmentation. The present invention was completed by experimentally verifying.

Domestic registered patent No. 10-1945274

The present invention was devised to solve the problems of the prior art as described above, and experimentally demonstrated that a composition containing desmethylxanthohumol as an active ingredient increases the expression of pro-collagen and inhibits melanin synthesis. As a result, the skin anti-aging or skin whitening effect was confirmed, and based on this, the present invention was completed.

Accordingly, the purpose of the present invention is to provide a cosmetic composition for preventing or improving skin aging or pigmentation, which contains a compound represented by the following formula (1), or a cosmetically acceptable salt thereof, as an active ingredient.

[Formula 1]

Another object of the present invention is to provide a cosmetic composition for skin whitening containing the compound represented by Formula 1 above, or a cosmetically acceptable salt thereof, as an active ingredient.

Another object of the present invention is to provide a food composition for preventing or improving skin aging or pigmentation, comprising the compound represented by Formula 1 above, or a foodologically acceptable salt thereof, as an active ingredient.

Another object of the present invention is to provide a pharmaceutical composition for preventing or treating pigmentation diseases, comprising the compound represented by Formula 1 above, or a pharmaceutically acceptable salt thereof, as an active ingredient.

However, the technical problem to be achieved by the present invention is not limited to the problems mentioned above, and other problems not mentioned can be clearly understood by those skilled in the art from the description below.

In order to achieve the object of the present invention, the present invention provides a cosmetic composition for preventing or improving skin aging or pigmentation, comprising a compound represented by the following formula (1) or a cosmetically acceptable salt thereof as an active ingredient. do.

[Formula 1]

Additionally, the present invention provides a cosmetic composition for skin whitening comprising the compound represented by Formula 1 above, or a cosmetically acceptable salt thereof, as an active ingredient.

In addition, the present invention provides a food composition for preventing or improving skin aging or pigmentation, comprising the compound represented by Formula 1 above, or a foodologically acceptable salt thereof, as an active ingredient.

Additionally, the present invention provides a pharmaceutical composition for preventing or treating pigmentation diseases, comprising the compound represented by Formula 1 above, or a pharmaceutically acceptable salt thereof, as an active ingredient.

In one embodiment of the present invention, the compound represented by Formula 1 may be characterized as increasing the expression of procollagen, but is not limited thereto.

In another embodiment of the present invention, the compound represented by Formula 1 may be characterized as inhibiting the synthesis of melanin, but is not limited thereto.

In another embodiment of the present invention, the composition may be characterized as preventing or improving skin aging caused by ultraviolet rays, but is not limited thereto.

In another embodiment of the present invention, the composition may be characterized as preventing or improving skin wrinkles, but is not limited thereto.

In another embodiment of the present invention, the composition may be characterized as promoting skin elasticity, but is not limited thereto.

In another embodiment of the present invention, the composition may be characterized as having a skin whitening effect, but is not limited thereto.

In another embodiment of the present invention, the pigmentation disease includes freckles, freckles, lentigo, age spots, moles, milk coffee spots, nevus of Ota, blue nevus, hyperpigmentation spots, hyperpigmentation after drug use, and pregnancy brown spots (gravidic spots). It may be characterized by, but is not limited to, one or more selected from the group consisting of chloasma, post-inflammatory hyperpigmentation due to wounds or dermatitis, senile pigmented spots, and solar lentigines.

In addition, the present invention provides a method for preventing or improving skin aging or pigmentation, comprising administering a composition containing the compound represented by Formula 1 as an active ingredient to an individual in need thereof; Alternatively, a skin whitening method is provided.

In addition, the present invention provides a method for preventing or improving skin aging or pigmentation, comprising administering a composition containing the compound represented by Formula 1 as an active ingredient to an individual in need thereof; Or, it provides a beauty method for skin whitening.

In addition, the present invention provides a method for preventing or improving skin aging or pigmentation using a composition containing the compound represented by Formula 1 as an active ingredient; Or it provides skin whitening use.

In addition, the present invention provides a method for preventing or improving skin aging or pigmentation using a composition containing the compound represented by Formula 1 as an active ingredient; Alternatively, it provides use for producing cosmetics used for skin whitening.

In addition, the present invention provides a method for preventing or improving skin aging or pigmentation, comprising administering a composition containing the compound represented by Formula 1 as an active ingredient to an individual in need thereof.

In addition, the present invention provides a use for preventing or improving skin aging or pigmentation of a composition containing the compound represented by Formula 1 above as an active ingredient.

In addition, the present invention provides the use of a composition containing the compound represented by Formula 1 as an active ingredient for producing cosmetics used to prevent or improve skin aging or pigmentation.

Additionally, the present invention provides the use of the compound represented by Formula 1 to produce a drug used for the prevention or treatment of pigmentation diseases.

The composition containing desmethylxanthohumol of the present invention as an active ingredient not only has low cytotoxicity, but also increases the expression of pro-collagen, which is reduced by ultraviolet rays, and inhibits the synthesis of melanin, thereby preventing skin aging or It is expected to be useful in preventing or improving pigmentation.

Figures 1a and 1b show the results of confirming the cytotoxicity of Xanthohumol and Desmethylxanthohumol in human skin fibroblasts (HDF) and B16 melanoma cells (B16F10) using MTT assay. .
Figure 2a shows the results confirming the effect of restoring the expression of Pro-COL1A1 (pro-collagen type 1 alpha 1), which was reduced by ultraviolet B rays, following treatment with xanthohumol, isoxanthohumol, and desmethylxanthohumol in human skin fibroblasts. It represents.
Figure 2b shows the results confirming the effect of restoring the expression of Pro-COL1A1 reduced by ultraviolet B rays in human skin fibroblasts by treatment with desmethylxanthohumol at different concentrations (5, 10, and 20 μM).
Figure 3 shows the results of confirming the degree of inhibition of melanin synthesis induced by α-MSH of xanthohumol, isoxanthohumol, and desmethylxanthohumol in B16 melanoma cells.

In one example of the present invention, human skin fibroblasts and B16 melanoma cells were treated with xanthohumol and desmethylxanthohumol, and then cell survival rate was confirmed. As a result, it was confirmed that desmethylxanthohumol has minimal cytotoxicity and can be used in cosmetics and foods without side effects (see Example 1).

In another example of the present invention, the expression of procollagen was confirmed after treating human skin fibroblasts with xanthohumol, isoxanthohumol, and desmethylxanthohumol. As a result, it was confirmed that the effect of desmethylxanthohumol on increasing procollagen expression was significantly superior to that of xanthohumol and isoxanthohumol, and that desmethylxanthohumol increased procollagen expression in a concentration-dependent manner (see Example 2). .

In another example of the present invention, the degree of inhibition of melanin synthesis was confirmed after treating B16 melanoma cells with xanthohumol, isoxanthohumol, and desmethylxanthohumol. As a result, it was confirmed that the skin whitening effect of desmethylxanthohumol was superior to that of xanthohumol and isoxanthohumol (see Example 3).

Hereinafter, the present invention will be described in detail.

The present invention provides a cosmetic composition for preventing or improving skin aging or pigmentation, comprising a compound represented by the following formula (1), or a cosmetically acceptable salt thereof, as an active ingredient. In addition, the present invention provides a cosmetic composition for skin whitening comprising a compound represented by the following formula (1), or a cosmetically acceptable salt thereof, as an active ingredient.

[Formula 1]

In the present invention, the compound represented by Formula 1 is (E)-3-(4-hydroxyphenyl)-1-[2,4,6-trihydroxy-3-(3-methylbut-2-enyl)phenyl]prop It may have the IUPAC name of -2-en-1-one, its molecular weight may be 340.4, and its chemical formula may be C ₂₀ H ₂₀ O ₅ . Additionally, in one embodiment, it is called desmethylxanthohumol, but it is not limited thereto.

In the present invention, the method of obtaining the compound may be chemically synthesized by a method known in the field to which the present invention pertains, or a commercially available material may be used, but is not limited thereto. Additionally, the compound may be isolated from hops, but is not limited thereto.

In the present invention, “Hop” is a plant of the Humulus genus Rosaceae family and is a raw material used in beer production. Secondary metabolites of hops are generally divided into polyphenols, essential oils, and resins (bitter acids) depending on their chemical structures. Representative compounds belonging to hop resin include humulone, which belongs to alpha acids (α-acids), and lupulon, which belongs to beta acids, and representative compounds of polyphenols include prenylated flavonoids. (prenylated flavonoid) family includes xanthohumol, isoxanthohumol, desmethylxanthohumol, and 6- or 8-prenylnaringenin.

Additionally, the compound may increase the expression of procollagen, but is not limited thereto. Additionally, the compound may inhibit the synthesis of melanin, but is not limited thereto.

The composition can prevent or improve skin aging caused by ultraviolet rays, and specifically prevent or improve skin aging caused by ultraviolet B rays, but is not limited thereto.

Additionally, the composition can prevent or improve skin wrinkles, but is not limited thereto. Additionally, the composition may improve skin elasticity, but is not limited thereto. Additionally, the composition may have a skin whitening effect, but is not limited thereto.

In the present invention, the “effect of preventing or improving skin wrinkles” refers to suppressing or inhibiting the formation of wrinkles on the skin or alleviating already formed wrinkles by increasing the expression of procollagen.

In the present invention, the “skin elasticity enhancement effect” refers to an increase in the elasticity of the skin, which promotes the expression of pro-collagen, suppressing or inhibiting the loss of skin elasticity, or alleviating already reduced elasticity. Or it refers to promoting it.

The formulation of the cosmetic composition according to the present invention includes skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutritional lotion, massage cream, nutritional cream, mist, moisture cream, hand cream, hand lotion, foundation, It may be in the form of essence, nutritional essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, cleansing oil, cleansing balm, body lotion, or body cleanser.

The cosmetic composition of the present invention may further include a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high molecular weight peptides, high molecular weight polysaccharides, and sphingolipids.

Water-soluble vitamins may be any that can be mixed into cosmetics, but examples include vitamin B1, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, and vitamin H. and their salts (thiamine hydrochloride, sodium ascorbate, etc.) or derivatives (sodium ascorbic acid-2-phosphate, magnesium ascorbic acid-2-phosphate, etc.) are also water-soluble vitamins that can be used in the present invention. Included. Water-soluble vitamins can be obtained by conventional methods such as microbial transformation, purification from microbial cultures, enzymatic methods, or chemical synthesis.

Oil-soluble vitamins can be anything that can be mixed into cosmetics, but examples include vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol), etc. , their derivatives (ascorbic palmitate, ascorbic stearate, ascorbic acid dipalmitate, dl-alpha tocopherol acetate, dl-alpha tocopherol nicotinic acid, vitamin E, DL-pantothenyl alcohol, D-pantothenyl alcohol, pantothenyl ethyl ether, etc.) are also included in the oil-soluble vitamins used in the present invention. Oil-soluble vitamins can be obtained by conventional methods such as microbial transformation, purification from microbial cultures, enzymatic or chemical synthesis.

Any polymer peptide that can be blended into cosmetics may be used, and examples include collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, and keratin. High molecular weight peptides can be purified and obtained by conventional methods such as purification from microbial culture media, enzymatic methods, or chemical synthesis, or they can usually be purified and used from natural products such as dermis of pigs or cows or silk fiber of silkworms.

The high molecular weight polysaccharide may be anything that can be blended into cosmetics, but examples include hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate, or its salts (sodium salt, etc.). For example, chondroitin sulfate or its salt can usually be purified and used from mammals or fish.

The sphingolipid may be any one that can be blended into cosmetics, and examples include ceramide, phytosphingosine, and sphingolipid. Sphingolipids can usually be purified by conventional methods from mammals, fish, shellfish, yeast, or plants, or obtained by chemical synthesis.

In addition to the above-mentioned essential ingredients, the cosmetic composition of the present invention may contain other ingredients usually blended in cosmetics as needed.

Other ingredients that may be added include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, disinfectants, antioxidants, plant extracts, pH adjusters, alcohol, colorants, fragrances, Examples include blood circulation promoters, cooling agents, antiperspirants, and purified water.

Examples of oil and fat components include ester-based fats and oils, hydrocarbon-based fats and oils, silicone-based fats and oils, fluorine-based fats and oils, animal fats and oils, and vegetable fats and oils.

Ester oils include glyceryl tri2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, and stearic acid. Butyl, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, adipine. Diisopropyl acid, isoalkyl neopentanoate, tri(caprylic, capric acid)glyceryl, trimethylolpropane tri2-ethylhexanoate, trimethylolpropane triisostearate, pentaelislitol tetra2-ethylhexanoate , cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinooleate, isostear laurate. Reyl, isotridecyl myristate, isocetyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, isopropyl isostearate, cetoester 2-ethylhexanoate Aryl, 2-ethylhexanoate stearyl, hexyl isostearate, ethylene glycol dioctanate, ethylene glycol dioleate, propylene glycol dicapric acid, di(capryl, capric acid) propylene glycol, propylene glycol dicaprylate, dicapric acid Neopentyl glycol prinate, neopentyl glycol dioctanate, glyceryl tricaprylate, glyceryl triundecylate, glyceryl triisopalmitate, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate. , octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerol oleic acid ester, polyglycerol isostearic acid ester, Triisocetyl citrate, triisoalkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, triethyl citrate, acetyltriethyl citrate, acetyltributyl citrate, trioctyl citrate, dimalate Isostearyl, 2-ethylhexyl hydroxystearate, di2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, Cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, phytsteryl isostearate, phytsteryl oleate, 12-stealoyl hydroxystearate isocetyl, 12-stealoyl hydride. Ester systems such as stearyl hydroxystearate and isostearyl 12-stealoylhydroxystearate can be mentioned.

Hydrocarbon-based fats and oils include squalene, liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybudene, microcrystalline wax, and petroleum jelly.

Silicone oils include polymethyl silicone, methylphenyl silicone, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane/methylcetyloxysiloxane copolymer, dimethylsiloxane/methylstealoxysiloxane copolymer, and alkyl. Modified silicone oil, amino-modified silicone oil, etc. can be mentioned.

Examples of fluorine-based fats and oils include perfluoropolyether.

Animal or plant oils include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, birdflower oil, soybean oil, corn oil, rapeseed oil, apricot oil, palm kernel oil, palm oil, castor oil, sunflower oil, and grape seed oil. , cottonseed oil, palm oil, cucumber nut oil, wheat germ oil, rice germ oil, shea butter, walnut colostrum oil, marker damia nut oil, meadow oil, egg yolk oil, beef tallow, horse oil, mink oil, orange rape oil, jojoba oil. , animal or plant oils such as candelier wax, carnaba wax, liquid lanolin, and hydrogenated castor oil.

Moisturizers include water-soluble low-molecular-weight moisturizers, oil-soluble molecular moisturizers, water-soluble polymers, and fat-soluble polymers.

Water-soluble low-molecular-weight moisturizers include serine, glutamine, sorbitol, mannitol, sodium pyrrolidone-carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol B (degree of polymerization n = 2 or more), and polypropylene. Examples include glycol (degree of polymerization n = 2 or more), polyglycerin B (degree of polymerization n = 2 or more), lactic acid, lactate, etc.

Examples of fat-soluble low-molecular-weight moisturizers include cholesterol and cholesterol esters.

Water-soluble polymers include carboxyvinyl polymer, polyaspartate, tragacanth, xanthan gum, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, water-soluble chitin, chitosan, and dextrin. You can.

Examples of oil-soluble polymers include polyvinylpyrrolidone/eicosene copolymer, polyvinylpyrrolidone/hexadecene copolymer, nitrocellulose, dextrin fatty acid ester, and polymer silicone.

Examples of emollients include long-chain acyl glutamic acid cholesteryl ester, hydroxystearic acid cholesteryl, 12-hydroxystearic acid, stearic acid, rosin acid, and lanolin fatty acid cholesteryl ester.

Examples of surfactants include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants.

Nonionic surfactants include self-emulsifying glycerin monostearate, propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE (polyoxyethylene), sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hydrogenated castor oil, POE castor oil, POE/POP (polyoxyethylene/polyoxypropylene) copolymer, POE/POP alkyl ether, polyether modified silicone, laurine Examples include acid alkanolamide, alkylamine oxide, and hydrogenated soybean phospholipid.

Anionic surfactants include fatty acid soap, alpha-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate, alkyl amide sulfate, alkyl phosphate, POE alkyl phosphate, and alkyl amide phosphate. , alkyloyl alkyl taurine salt, N-acylamino acid salt, POE alkyl ether carboxylate, alkyl sulfosuccinate, sodium alkyl sulfoacetate, acylated hydrolyzed collagen peptide salt, perfluoroalkyl phosphate ester, etc. .

Cationic surfactants include alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, and cationic surfactant. Benzalkonium, diethylaminoethylamide stearate, dimethylaminopropylamide stearate, quaternary ammonium salt of lanolin derivative, etc. are mentioned.

Amphoteric surfactants include carboxy beta type, amide beta type, sulfo beta type, hydroxy sulfo beta type, amide sulfo beta type, phosphobeta type, aminocarboxylate type, imidazoline derivative type, and amide amine type. Amphoteric surfactants, etc. can be mentioned.

Organic and inorganic pigments include silicic acid, anhydrous silicic acid, magnesium silicate, talc, sericite, mica, kaolin, bengala, clay, bentonite, titanium-coated mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, and aluminum oxide. Inorganic pigments such as calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, ultramarine blue, chromium oxide, chromium hydroxide, calamine and complexes thereof; Polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin, fluorine resin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, divinylbenzene/styrene copolymer, Examples include organic pigments such as silk powder, cellulose, CI pigment yellow, and CI pigment orange, and complex pigments of these inorganic pigments and organic pigments.

Examples of organic powder include metal soap such as calcium stearate; Alkyl phosphate metal salts such as sodium zinc cetilate, zinc laurylate, and calcium laurylate; Acyl amino acid polyvalent metal salts such as N-lauroyl-beta-alanine calcium, N-lauroyl-beta-alanine zinc, and N-lauroyl glycine calcium; Amidesulfonic acid polyvalent metal salts such as N-lauroyl-taurine calcium and N-palmitoyl-taurine calcium; N such as N-epsilon-lauroyl-L-lysine, N-epsilon-palmitoylizine, N-alpha-paritoylolnithine, N-alpha-lauroylarginine, N-alpha-hydrogenated beef tallow fatty acid acylarginine, etc. -Acyl basic amino acid; N-acyl polypeptides such as N-lauroylglycylglycine; Alpha-amino fatty acids such as alpha-aminocaprylic acid and alpha-aminolauric acid; Examples include polyethylene, polypropylene, nylon, polymethyl methacrylate, polystyrene, divinylbenzene/styrene copolymer, and ethylene tetrafluoride.

UV absorbers include para-aminobenzoic acid, ethyl para-aminobenzoate, amyl para-aminobenzoate, octyl para-aminobenzoate, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomenthyl salicylate, and benzyl cinnamate. , paramethoxycinnamic acid-2-ethoxyethyl, paramethoxycinnamic acid octyl, diparamethoxycinnamic acid mono-2-ethylhexane glyceryl, paramethoxycinnamic acid isopropyl, diisopropylㆍdiisopropylcinnamic acid ester mixture, uro Kaninic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone disulfonate sodium, dihydroxybenzophenone , tetrahydroxybenzophenone, 4-tert-butyl-4'-methoxydibenzoylmethane, 2,4,6-trianilino-p-(carbo-2'-ethylhexyl-1'-oxy)-1 , 3,5-triazine, 2-(2-hydroxy-5-methylphenyl)benzotriazole, etc.

Disinfectants include hinokitiol, triclosan, trichlorohydroxydiphenyl ether, chlorhexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid, zincphyllithione, benzalkonium chloride, and photosensitive. Examples include Sono 301, sodium mononitroguaiacol, and undecirenic acid.

Antioxidants include butylhydroxyanisole, propyl gallate, and elisorbic acid.

Examples of pH adjusters include citric acid, sodium citrate, malic acid, sodium malate, fumal acid, sodium fumalate, succinic acid, sodium succinate, sodium hydroxide, and sodium monohydrogen phosphate.

Examples of alcohol include higher alcohols such as cetyl alcohol.

In addition, the ingredients that can be added are not limited to this, and any of the above ingredients can be mixed within the range that does not impair the purpose and effect of the present invention, but in an amount of 0.01-5% by weight or 0.01-3% based on the total weight. Can be formulated in % weight percentages.

When the formulation of the present invention is a lotion, paste, cream or gel, the carrier ingredients include animal fiber, plant fiber, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide. It can be used.

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder can be used as the carrier ingredient. In particular, when the formulation is a spray, chlorofluorohydrocarbon and propane may be used as carrier ingredients. /May contain propellants such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solvating agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 , 3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol or fatty acid esters of sorbitan.

When the formulation of the present invention is a suspension, the carrier ingredients include water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, and microcrystalline Cellulose, aluminum metahydroxide, bentonite, agar, or tracant may be used.

When the formulation of the present invention is a surfactant-containing cleansing agent, the carrier ingredients include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, and fatty acid amide. Ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, linoline derivative, or ethoxylated glycerol fatty acid ester can be used.

Additionally, the present invention provides a food composition for preventing or improving skin aging or pigmentation, comprising a compound represented by the following formula (1), or a foodologically acceptable salt thereof, as an active ingredient.

[Formula 1]

In the present invention, the term “foodologically acceptable salt” includes salts derived from foodologically acceptable organic acids, inorganic acids, or bases.

When using the compound represented by Formula 1 of the present invention, or a foodologically acceptable salt thereof, as a food additive, the compound represented by Formula 1, or a foodologically acceptable salt thereof, is added as is or added to other foods or food products. It can be used together with the ingredients and can be used appropriately according to conventional methods. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment). In general, when manufacturing food or beverages, the compound represented by Formula 1 of the present invention, or a foodologically acceptable salt thereof, may be added in an amount of 15% by weight or less, or 10% by weight or less, based on the raw materials. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.

There are no special restrictions on the types of foods above. Examples of foods to which the above substances can be added include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, These include alcoholic beverages and vitamin complexes, and include all health functional foods in the conventional sense.

The health drink composition according to the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients, like conventional drinks. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a sweetener, natural sweeteners such as thaumatin and stevia extract or synthetic sweeteners such as saccharin and aspartame can be used. The proportion of natural carbohydrates is generally about 0.01-0.20 g, or about 0.04-0.10 g per 100 mL of the composition of the present invention.

In addition to the above, the composition of the present invention contains various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, It may contain carbonating agents used in carbonated drinks. In addition, the composition of the present invention may contain pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These ingredients can be used independently or in combination. The ratio of these additives is not very important, but is generally selected in the range of 0.01-0.20 parts by weight per 100 parts by weight of the composition of the present invention.

The health functional food has the advantage of having better effects when consumed in the form of inner beauty food. The inner beauty is a food called 'edible cosmetics or beauty food'. It refers to food that changes the skin constitution to a healthy one by absorbing various ingredients that are good for the skin into the body. It refers to the food that changes the skin constitution to a healthy one by selecting cosmetics that suit your skin type. You can choose and consume inner beauty foods that suit each individual, considering their skin condition and lifestyle. For example, when cosmetics containing the cosmetic composition and inner beauty food containing the desmethylxanthohumol are mixed, the effect is significantly higher compared to using only cosmetics or drugs, resulting in a more effective skin aging prevention effect. It can have advantages.

The present invention provides a pharmaceutical composition for preventing or treating pigmentation diseases, comprising a compound represented by the following formula (1), or a pharmaceutically acceptable salt thereof, as an active ingredient.

[Formula 1]

In the present invention, “pigmentation” refers to any disease or disease of the skin caused by discoloration of the skin (pigmentation) or proliferation of abnormally pigmented cells, and is interchangeable with hyperpigmentation. It can be used negatively. Skin pigmentation includes excessive or unwanted pigmentation. Factors such as aging, environmental stress, and UV exposure can be potential causes of skin pigmentation. Skin pigmentation of the present invention may be due to an increase in one or more different types of melanin biosynthesized in the skin and/or hair follicles and deposited on the hair or skin compared to the patient's baseline pigmentation. In the present invention, pigmentation diseases include freckles, freckles, lentigines, age spots, moles, milk coffee spots, nevus of Ota, blue nevus, hyperpigmentation spots, hyperpigmentation after drug use, gravidic chloasma, and wounds. Or, it may be one or more selected from the group consisting of post-inflammatory hyperpigmentation due to dermatitis, senile pigmented spots, and solar lentigines, but is not limited thereto.

The present invention may also include a pharmaceutically acceptable salt of the compound represented by Formula 1 above as an active ingredient. As used herein, the term “pharmaceutically acceptable salt” includes salts derived from pharmaceutically acceptable inorganic acids, organic acids, or bases.

Examples of suitable acids include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, formic acid. , benzoic acid, malonic acid, gluconic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, etc. Acid addition salts can be prepared by conventional methods, for example, by dissolving the compound in an excessive amount of aqueous acid and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone, or acetonitrile. It can also be prepared by heating equimolar amounts of the compound and an acid or alcohol in water and then evaporating the mixture to dryness, or suction filtering the precipitated salt.

Salts derived from suitable bases may include, but are not limited to, alkali metals such as sodium and potassium, alkaline earth metals such as magnesium, and ammonium. The alkali metal or alkaline earth metal salt can be obtained, for example, by dissolving the compound in an excessive amount of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. At this time, it is particularly pharmaceutically suitable to produce sodium, potassium or calcium salts as metal salts, and the corresponding silver salts can be obtained by reacting an alkali metal or alkaline earth metal salt with an appropriate silver salt (eg, silver nitrate).

The content of the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof in the composition of the present invention can be appropriately adjusted depending on the symptoms of the disease, the degree of progression of the symptoms, the patient's condition, etc., for example, based on the total weight of the composition. It may be 0.0001 to 99.9% by weight, or 0.001 to 50% by weight, but is not limited thereto. The content ratio is a value based on the dry amount with the solvent removed.

The pharmaceutical composition according to the present invention may further include appropriate carriers, excipients, and diluents commonly used in the preparation of pharmaceutical compositions. The excipient may be, for example, one or more selected from the group consisting of diluents, binders, disintegrants, lubricants, adsorbents, humectants, film-coating materials, and controlled-release additives.

The pharmaceutical composition according to the present invention can be prepared as powder, granules, sustained-release granules, enteric-coated granules, solutions, eye drops, ellipsis, emulsions, suspensions, spirits, troches, perfumes, and limonadese according to conventional methods. , tablets, sustained-release tablets, enteric-coated tablets, sublingual tablets, hard capsules, soft capsules, sustained-release capsules, enteric-coated capsules, pills, tinctures, soft extracts, dry extracts, liquid extracts, injections, capsules, perfusate, It can be formulated and used in the form of external preparations such as warning agents, lotions, paste preparations, sprays, inhalants, patches, sterilized injection solutions, or aerosols, and the external preparations include creams, gels, patches, sprays, ointments, and warning agents. , it may have a dosage form such as lotion, liniment, pasta, or cataplasma.

Carriers, excipients, and diluents that may be included in the pharmaceutical composition according to the present invention include lactose, dextrose, sucrose, oligosaccharides, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, and calcium. These include phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

Additives to tablets, powders, granules, capsules, pills, and troches according to the present invention include corn starch, potato starch, wheat starch, lactose, white sugar, glucose, fructose, di-mannitol, precipitated calcium carbonate, synthetic aluminum silicate, and phosphoric acid. Calcium monohydrogen, calcium sulfate, sodium chloride, sodium bicarbonate, purified lanolin, microcrystalline cellulose, dextrin, sodium alginate, methylcellulose, sodium carboxymethylcellulose, kaolin, urea, colloidal silica gel, hydroxypropyl starch, hydroxypropylmethyl. Excipients such as cellulose (HPMC), HPMC 1928, HPMC 2208, HPMC 2906, HPMC 2910, propylene glycol, casein, calcium lactate, and Primogel; Gelatin, gum arabic, ethanol, agar powder, cellulose acetate phthalate, carboxymethyl cellulose, calcium carboxymethyl cellulose, glucose, purified water, sodium caseinate, glycerin, stearic acid, sodium carboxymethyl cellulose, sodium methyl cellulose, methyl cellulose, microcrystalline cellulose, dextrin. , hydroxycellulose, hydroxypropyl starch, hydroxymethylcellulose, refined shellac, starch, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, etc. binders can be used, Hydroxypropyl methyl cellulose, corn starch, agar powder, methyl cellulose, bentonite, hydroxypropyl starch, sodium carboxymethyl cellulose, sodium alginate, calcium carboxymethyl cellulose, calcium citrate, sodium lauryl sulfate, silicic acid anhydride, 1-hydroxy Propylcellulose, dextran, ion exchange resin, polyvinyl acetate, formaldehyde-treated casein and gelatin, alginic acid, amylose, guar gum, sodium bicarbonate, polyvinylpyrrolidone, calcium phosphate, gelled starch, gum arabic, Disintegrants such as amylopectin, pectin, sodium polyphosphate, ethyl cellulose, white sugar, magnesium aluminum silicate, di-sorbitol solution, light anhydrous silicic acid; Calcium stearate, magnesium stearate, stearic acid, hydrogenated vegetable oil, talc, lycopodium, kaolin, petrolatum, sodium stearate, cacao fat, sodium salicylate, magnesium salicylate, polyethylene glycol (PEG) 4000, PEG 6000, liquid paraffin, hydrogen. Added soybean oil (Lubri wax), aluminum stearate, zinc stearate, sodium lauryl sulfate, magnesium oxide, Macrogol, synthetic aluminum silicate, silicic anhydride, higher fatty acids, higher alcohol, silicone oil, paraffin oil, polyethylene glycol fatty acid ether, Lubricants such as starch, sodium chloride, sodium acetate, sodium oleate, dl-leucine, and light anhydrous silicic acid can be used.

Additives for the liquid according to the present invention include water, dilute hydrochloric acid, dilute sulfuric acid, sodium citrate, sucrose monostearate, polyoxyethylene sorbitol fatty acid esters (twin esters), polyoxyethylene monoalkyl ethers, lanolin ethers, Lanolin esters, acetic acid, hydrochloric acid, aqueous ammonia, ammonium carbonate, potassium hydroxide, sodium hydroxide, prolamine, polyvinylpyrrolidone, ethyl cellulose, sodium carboxymethyl cellulose, etc. can be used.

A solution of white sugar, other sugars, or sweeteners, etc. may be used in the syrup according to the present invention, and if necessary, flavoring agents, colorants, preservatives, stabilizers, suspending agents, emulsifiers, thickening agents, etc. may be used.

Purified water can be used in the emulsion according to the present invention, and emulsifiers, preservatives, stabilizers, fragrances, etc. can be used as needed.

Suspensions according to the present invention include acacia, tragacantha, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, sodium alginate, hydroxypropylmethylcellulose (HPMC), HPMC 1828, HPMC 2906, HPMC 2910, etc. Topics may be used, and surfactants, preservatives, stabilizers, colorants, and fragrances may be used as needed.

Injections according to the present invention include distilled water for injection, 0.9% sodium chloride injection, IV solution, dextrose injection, dextrose + sodium chloride injection, PEG, lactated IV solution, ethanol, propylene glycol, non-volatile oil - sesame oil. solvents such as cottonseed oil, peanut oil, soybean oil, corn oil, ethyl oleate, isopropyl myristic acid, and benzene benzoate; Solubilizers such as sodium benzoate, sodium salicylate, sodium acetate, urea, urethane, monoethylacetamide, butazolidine, propylene glycol, Tween, nicotinic acid amide, hexamine, and dimethylacetamide; Weak acids and their salts (acetic acid and sodium acetate), weak bases and their salts (ammonia and ammonium acetate), organic compounds, proteins, albumin, peptone, and buffering agents such as gums; Isotonic agents such as sodium chloride; Stabilizers such as sodium bisulfite (NaHSO ₃ ) carbon dioxide gas, sodium metabisulfite (Na ₂ S ₂ O ₅ ), sodium sulfite (Na ₂ SO ₃ ), nitrogen gas (N ₂ ), and ethylenediaminetetraacetic acid; Sulfurizing agents such as sodium bisulfide 0.1%, sodium formaldehyde sulfoxylate, thiourea, disodium ethylenediaminetetraacetate, and acetone sodium bisulfite; Analgesics such as benzyl alcohol, chlorobutanol, procaine hydrochloride, glucose, and calcium gluconate; It may contain suspending agents such as CM sodium, sodium alginate, Tween 80, and aluminum monostearate.

Suppositories according to the present invention include cacao oil, lanolin, witepsol, polyethylene glycol, glycerogelatin, methylcellulose, carboxymethylcellulose, a mixture of stearic acid and oleic acid, Subanal, cottonseed oil, peanut oil, palm oil, cacao butter + Cholesterol, lecithin, Lanet wax, glycerol monostearate, Tween or Span, Imhausen, monolene (propylene glycol monostearate), glycerin, Adeps solidus, Buytyrum Tego -G), Cebes Pharma 16, Hexalide Base 95, Cotomar, Hydrocote SP, S-70-XXA, S-70-XX75 (S-70-XX95), Hydro Hydrokote 25, Hydrokote 711, Idropostal, Massa estrarium (A, AS, B, C, D, E, I, T), Massa-MF, Massaupol, Masupol-15, Neosupostal-N, Paramound-B, Suposiro (OSI, OSIX, A, B, C, D, H, L), suppositories type IV (AB, B, A, BC, BBG, E, BGF, C, D, 299), Supostal (N, Es), Wecobi (W, R, S, M, Fs), Tegestor triglyceride base (TG-95, MA, 57) and The same mechanism can be used.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include the extract with at least one excipient, such as starch, calcium carbonate, and sucrose. ) or prepared by mixing lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium styrate talc are also used.

Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. there is. Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate.

The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat the disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type, severity, drug activity, and It can be determined based on factors including sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, drugs used simultaneously, and other factors well known in the medical field.

The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect with the minimum amount without side effects, and this can be easily determined by a person skilled in the art to which the present invention pertains.

The pharmaceutical composition of the present invention can be administered to an individual through various routes. All modes of administration are contemplated, including oral administration, subcutaneous injection, intraperitoneal administration, intravenous injection, intramuscular injection, paraspinal space (intrathecal) injection, sublingual administration, buccal administration, intrarectal injection, vaginal injection. It can be administered by internal insertion, ocular administration, ear administration, nasal administration, inhalation, spraying through the mouth or nose, dermal administration, transdermal administration, etc.

The pharmaceutical composition of the present invention is determined depending on the type of drug as the active ingredient along with various related factors such as the disease to be treated, the route of administration, the patient's age, gender, weight, and severity of the disease.

In the present invention, “individual” refers to a subject in need of treatment for a disease, and more specifically, human or non-human primates, mice, rats, dogs, cats, horses, cows, etc. refers to mammals of

In the present invention, “administration” means providing a given composition of the present invention to an individual by any appropriate method.

In the present invention, “prevention” refers to any action that suppresses or delays the onset of the desired disease, and “treatment” refers to the improvement or improvement of the desired disease and its associated metabolic abnormalities by administration of the pharmaceutical composition according to the present invention. It refers to all actions that are beneficially changed, and “improvement” refers to all actions that reduce parameters related to the target disease, such as the degree of symptoms, by administering the composition according to the present invention.

Hereinafter, the following examples are presented to aid understanding of the present invention. However, the following examples are provided only to make the present invention easier to understand, and the content of the present invention is not limited by the following examples.

Example 1. Confirmation of cytotoxicity of xanthohumol and desmethylxanthohumol in human skin fibroblasts and melanin-producing cells

To test the cytotoxicity of xanthohumol and desmethylxanthohumol, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed using human fibroblasts. First, human skin fibroblasts and B16 melanoma cells were cultured in DMEM (Dulbecco's Modified Eagle's Medium) containing 10% fetal bovine serum (FBS) and penicillin-streptomycin (GIBCO ^® Invitrogen, Auckland, NZ). Using this, 96-well plates were seeded at a concentration of 5×10 ³ and 0.3×10 ³ cells/well, respectively, and cultured for 24 hours at 37°C and 5% CO ₂ . In addition, 200 mg of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) powder was dissolved in 40 mL of PBS and filtered to prepare a 5 mg/mL MTT solution. 24 hours after seeding, medium containing xanthohumol and desmethylxanthohumol, respectively, was added. After 24 hours for skin fibroblasts and 96 hours for B16 melanoma cells, 20 μL of 5 mg/mL MTT solution was added. Then, after culturing for 2 hours under the same conditions (37°C, 5% CO ₂ ), formazan formation was observed. After removing the MTT reagent and adding 200 μL of DMSO (dimethyl sulfoxide) to dissolve the resulting formazan, the absorbance was measured at a wavelength of 570 nm using a microplate reader (Sunrise-Basic Tecan, Austria). . Cell viability was calculated using Equation 1 below. The results are shown in Figures 1A and 1B.

[Equation 1]

As shown in Figure 1a, it was confirmed that neither xanthohumol nor desmethylxanthohumol showed toxicity in human skin fibroblasts.

In addition, as shown in Figure 1b, it was confirmed that, unlike desmethylxanthohumol, in B16 melanoma cells, xanthohumol showed strong toxicity with a cell viability of less than 20% even at a low concentration of 20μM.

This means that since the cytotoxicity of desmethylxanthohumol is minimal, it can be used in cosmetics and foods without side effects.

Example 2. Confirmation of the effect of xanthohumol, isoxanthohumol and desmethylxanthohumol on improving Pro-COL1A1 expression suppressed by ultraviolet B

Human dermal fibroblasts (HDF) were cultured in DMEM (Dulbecco's Modified Eagle's Medium) containing 10% fetal bovine serum (FBS) and penicillin-streptomycin (GIBCO ^® Invitrogen, Auckland, NZ) at 37°C for 5 days. Cultured under % CO ₂ conditions. Then, xanthohumol, isoxanthohumol, and desmethylxanthohumol were dissolved in DMSO (dimethyl sulfoxide) and treated at different concentrations. After removing the medium, it was washed with PBS (Phosphate Buffered Saline) to remove the serum component in the medium, and then irradiated with ultraviolet B light at 20 mJ/cm ² using a Vilber Lourmat (BioLink Crosslinker, France). Then, the cells were cultured for 12 hours and washed twice with PBS. Additionally, cells attached to the bottom were recovered using a lysis buffer and centrifuged at 14,000 rpm for 10 minutes. After taking each supernatant, using BSA (bovine serum albumin) as a standard, the protein concentration of each cell supernatant was measured using a protein assay kit (Bio-Rad, USA) according to the method used. Quantified. From each protein extract, 6-7 μg of protein was denatured and separated using an 8% SDS-PAGE (sodium dodecyl sulphate-polyacrylamide gel electrophoresis) gel, and transferred to a PVDF membrane (Polyvinylidene fluoride membrane) at 100 mA for 2 hours. . Afterwards, it was soaked in a TBST solution containing 5% skim milk and reacted overnight to block non-specific proteins and washed twice with TBST. At this time, Pro-COL1A1 goat polyclonal IgG (Santacruz, USA) was used as an antibody diluted 1:1000 in TBST solution, and reacted at 4°C for 3 hours. As a secondary antibody, HRP (Horseradish peroxidase)-conjugated anti-goat IgG (Santacruz, USA) was used at a dilution of 1:5000, and reacted at 4°C for 1 hour and 30 minutes. Afterwards, it was washed again with TBST four times and detected using an ECL kit (Amersham, Denver, USA). The results are shown in Figures 2a and 2b.

As shown in Figure 2a, desmethylxanthohumol most significantly increased the expression of Pro-COL1A1 (pro-collagen type 1 alpha 1), which was suppressed by ultraviolet B rays, in human skin fibroblasts.

Additionally, as shown in Figure 2b, it was confirmed that desmethylxanthohumol increases the expression of Pro-COL1A1 (pro-collagen type 1 alpha 1), which is suppressed by ultraviolet B, in a concentration-dependent manner.

This means that desmethylxanthohumol can be used as a composition for preventing or improving skin aging by improving skin wrinkles and improving elasticity.

Example 3. Confirmation of melanin synthesis inhibitory effect of xanthohumol, isoxanthohumol, and desmethylxanthohumol in mouse-derived B16 melanoma cells

To confirm the melanin synthesis inhibitory effect of xanthohumol, isoxanthohumol, and desmethylxanthohumol, melanin content assay was performed using mouse-derived B16 melanoma cells. Specifically, B16 melanoma cells were seeded in a 6-well plate at 4 × 10³ cells/well and cultured for 24 hours under conditions of 37°C and 5% CO ₂ using DMEM medium containing 10% FBS. Afterwards, the cells were treated with xanthohumol, isoxanthohumol, and desmethylxanthohumol at concentrations of 1, 10, and 10 μM, respectively, and with arbutin at a concentration of 50 μg/mL. After 1 hour, α-MSH (melanocyte-stimulating hormone, Sigma, USA) was added to the cell culture medium to a final concentration of 100 nM. Then, they were cultured again for 4 days under the same conditions (37°C, 5% CO ₂ ). At this time, the sample and cells not treated with α-MSH were used as the untreated control, cells treated only with α-MSH were used as the positive control, and cells treated with α-MSH and arbutin were used as the negative control.

After the cells were cultured until the bottom of the well was more than 80% filled, the medium was removed and washed twice with cold PBS to measure the amount of melanin synthesized by the cells. Afterwards, the adsorbed cells were separated by treatment with trypsin (GIBCO, USA) and the cells were recovered. The recovered cells were transferred to an effendrof tube and centrifuged at 14,000 rpm for 10 minutes. Afterwards, remove the supernatant, add 1N sodium hydroxide (NaOH) solution, dissolve the cell pellet in a water bath at 60°C for about 15 to 30 minutes, and plate 405 using a microplate reader in a 96-well plate. Absorbance was measured at a wavelength of ㎚. The results are shown in Figure 3.

As shown in Figure 3, isoxanthohumol did not inhibit melanin synthesis induced by α-MSH in B16 melanoma cells. Meanwhile, xanthohumol and desmethylxanthohumol showed an inhibitory effect on melanin production, but desmethylxanthohumol showed a better inhibitory effect.

This means that desmethylxanthohumol can be used to prevent or improve skin pigmentation; This means that it can be used as a skin whitening composition.

Through the above results, it can be seen that the composition containing desmethylxanthohumol of the present invention increases the expression of pro-collagen and is effective in preventing and improving skin aging by improving skin wrinkles and promoting elasticity. Confirmed; It was confirmed that it suppresses melanin production and is effective in preventing and improving skin pigmentation. Through this, it was confirmed that the composition can be used to prevent or improve skin aging or pigmentation.

The description of the present invention stated above is for illustrative purposes, and a person skilled in the art to which the present invention pertains can understand that it can be easily modified into other specific forms without changing the technical idea or essential features of the present invention. There will be. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive.

Claims (17)

A cosmetic composition for preventing or improving skin aging or pigmentation, comprising a compound represented by the following formula (1), or a cosmetically acceptable salt thereof, as an active ingredient.
[Formula 1]

According to paragraph 1,
A cosmetic composition, wherein the compound represented by Formula 1 increases the expression of procollagen.
According to paragraph 1,
A cosmetic composition, wherein the compound represented by Formula 1 inhibits the synthesis of melanin.
According to paragraph 1,
The composition is a cosmetic composition characterized in that it prevents or improves skin aging caused by ultraviolet rays.
According to paragraph 1,
The composition is a cosmetic composition characterized in that it prevents or improves skin wrinkles.
According to paragraph 1,
A cosmetic composition, characterized in that the composition promotes skin elasticity.
According to paragraph 1,
A cosmetic composition, characterized in that the composition has a skin whitening effect.
A cosmetic composition for skin whitening comprising a compound represented by the following formula (1), or a cosmetically acceptable salt thereof, as an active ingredient.

A food composition for preventing or improving skin aging or pigmentation, comprising a compound represented by the following formula (1), or a foodologically acceptable salt thereof, as an active ingredient.
[Formula 1]

According to clause 9,
A food composition wherein the compound represented by Formula 1 increases the expression of procollagen.
According to clause 9,
The compound represented by Formula 1 is a food composition characterized in that it inhibits the synthesis of melanin.
According to clause 9,
A food composition characterized in that the composition prevents or improves skin aging caused by ultraviolet rays.
According to clause 9,
A food composition characterized in that the composition prevents or improves skin wrinkles.
According to clause 9,
A food composition, characterized in that the composition promotes skin elasticity.
According to clause 9,
A food composition, characterized in that the composition has a skin whitening effect.
A pharmaceutical composition for preventing or treating pigmentation diseases, comprising a compound represented by the following formula (1), or a pharmaceutically acceptable salt thereof, as an active ingredient.
[Formula 1]

According to clause 16,
The above pigmentation diseases include freckles, freckles, lentigines, age spots, moles, milk coffee spots, nevus of Ota, blue nevus, hyperpigmentation spots, hyperpigmentation after drug use, gravidic chlorasma, wounds or dermatitis. A pharmaceutical composition, characterized in that at least one selected from the group consisting of post-inflammatory hyperpigmentation, senile pigmentation, and solar lentigines.