KR20200050292A - New composition for improving skin conditions - Google Patents

Abstract

The present invention relates to a composition for improving skin condition which comprises a derivative of a compound represented by chemical formula (I) or a pharmacologically acceptable salt thereof. In the chemical formula (I), X is hydrogen or methoxy, and R is a C1 to C20 linear or branched alkyl group.

Description

Composition for improving skin conditions {New composition for improving skin conditions}

The present invention relates to skin regeneration, wrinkle improvement, anti-inflammatory and / or antioxidant compositions, and more specifically, an external preparation for skin, specifically a cosmetic or pharmaceutical composition, has fewer side effects and is safe for the human body and is excellent for skin regeneration, wrinkle improvement, anti-inflammatory and Has antioxidant effect.

Collagen is a major matrix protein produced by fibroblasts in the skin, and is present in the extracellular epilepsy. Its main functions are known as skin firmness, connective tissue resistance and binding ability, support of cell adhesion, induction of cell division and differentiation, etc. . This collagen is reduced by age and photoaging by ultraviolet irradiation, which is closely related to the formation of wrinkles on the skin. In addition, as recent extensive research on skin aging has developed, important functions of collagen in skin have been revealed.

Retinoic acid, placenta protein, betulinic acid, etc. have been reported as ingredients that promote collagen synthesis and show wrinkle improvement effects. However, the above ingredients have a problem in that the amount of use is limited due to safety problems such as irritation and redness when applied to the skin, or the efficacy is insignificant, so that an effect of substantially improving skin function cannot be expected.

On the other hand, free radicals introduced from the outside or generated in the living body cause many problems such as promoting aging of the living body or generating cancer. Therefore, development and research on antioxidants that inhibit oxidation by free radicals have been actively conducted. Antioxidants are widely distributed in nature, and many phenolic compounds, flavonoids, tocopherols, vitamin C, and selenium are known in fruits and vegetables. However, the antioxidants present in nature cannot be expected to have a substantially sufficient effect when applied to the skin. Therefore, although synthetic antioxidants having excellent antioxidant power and low price are frequently used, their use is limited due to safety concerns such as side effects.

In addition, inflammation is an immune response of the human body that responds to wounds or diseases, and oxidative stress such as ultraviolet rays or free radicals activates inflammatory factors, causing various diseases and aging. It is called anti-inflammatory, which acts to remove inflammatory sources, reduce biological reactions, and symptoms. Nonsteroidal anti-inflammatory drugs include ibuprofen, indomethacin, and steroid-based anti-inflammatory drugs, prednisolone, Dexamethasone; and the like. These materials have a problem in that the amount of use is limited or the effect is insignificant due to safety problems for the skin, and thus an anti-inflammatory effect in the human body cannot be expected.

Therefore, there is an urgent need for the development of a material that is safe for a living body, stable over time, and above all, has a skin regeneration, wrinkle improvement, antioxidant and anti-inflammatory effect superior to existing materials.

The present invention is to provide a composition for external application for skin having no side effects on skin and having excellent skin regeneration, wrinkle improvement, antioxidant and anti-inflammatory effects.

The above object is a composition for improving skin comprising a derivative of a compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof as an active ingredient:

(I)

In the above formula, X is hydrogen or methoxy, and R is a C1 to C20 linear or branched alkyl group.

Since the compound according to the present invention has no side effects on the skin, and exhibits skin regeneration, wrinkle improvement, antioxidant and anti-inflammatory effects, the composition containing it is used as a composition for skin regeneration, wrinkle improvement, antioxidant and anti-inflammatory It is possible.

The present invention provides a composition for improving skin, comprising a derivative of a compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof as an active ingredient, having excellent skin regeneration, wrinkle improvement, antioxidant and anti-inflammatory effects. .

(I)

In the above formula, X is hydrogen or methoxy, and R is a C1 to C20 linear or branched alkyl group.

Hereinafter, the present invention will be described in more detail.

The compound of the present invention dissolves the aromatic compound in a suitable organic solvent as shown in the following reaction formula, and then one or two or more alkyl halides are mixed and slowly added dropwise at an appropriate equivalent ratio to ester reaction or ether reaction. It can be obtained through, or it can be obtained by performing a hydrogenation reaction (hydrogenation) again. At this time, the organic solvent usable for the reaction is not particularly limited, and examples thereof include dichloromethane, chloroform, tetrahydrofuran, acetonitrile, dimethylformamide, pyridine, and dimethylformamide. In particular, sodium hydride (NaH) or potassium carbonate (K ₂ CO ₃ ) can be used as a reaction catalyst.

[Scheme 1]

In Reaction Scheme 1, R is C _1-20 linear or branched alkyl, and X is hydrogen or methoxy.

The present invention also provides a composition for external application for skin regeneration, wrinkle improvement, antioxidant and anti-inflammatory skin containing the compound of the general formula (I) as an active ingredient.

The composition comprising the compound of the present invention may further include a suitable carrier, excipient or diluent according to a conventional method.

Carriers, excipients and diluents that may be included in the compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

Compositions comprising the compounds of the present invention are formulated in the form of oral dosage forms, external preparations, suppositories or sterile injectable solutions, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc. Can be used.

Specifically, in the case of formulation, it may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc., which are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include at least one excipient in the extract, for example, starch, calcium carbonate, sucrose ), Can be prepared by mixing lactose, gelatin, and the like. In addition, lubricants such as magnesium stearate and talc may be used in addition to simple excipients. Liquid preparations for oral use include suspending agents, intravenous solutions, emulsions, syrups, etc.In addition to the commonly used simple diluents, water and liquid paraffin, various excipients, such as wetting agents, sweeteners, fragrances, preservatives, etc. Can be. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, and glycerogelatin may be used.

The composition for skin regeneration, wrinkle improvement, antioxidant and anti-inflammatory comprising the compound of the formula (I) of the present invention as an active ingredient is a formulation for external application for skin that can be applied to the skin such as cream, gel, patch, spray, ointment, warning Preparation, lotion, linement, pasta or cataplasma may be prepared and used as a pharmaceutical composition in the form of an external preparation for skin, but is not limited thereto.

The preferred dosage of the compound of formula (I) of the present invention or a pharmacologically acceptable salt thereof depends on the patient's condition and body weight, the degree of disease, the drug form, the route and duration of administration, but will be appropriately selected by those skilled in the art. Can be. However, for the desired effect, the compound of the present invention is administered at 0.0001 to 100mg / kg per day, preferably 0.001 to 10mg / kg. The administration may be administered once a day, or may be divided into several times. The above dosage does not limit the scope of the present invention in any way.

The compounding amount of the compounds according to the present invention in the pharmaceutical composition for external application for skin is preferably 0.0001 to 20% by weight relative to the total weight of the composition, more preferably 0.001 to 10% by weight, which is less than 0.001% by weight. This is because it is difficult to expect an increase in the effect even if it is blended if there is a concern and it exceeds 20% by weight.

In addition, the pharmaceutical dosage forms of the compounds of the present invention may also be used in the form of their pharmaceutically acceptable salts, and may also be used alone or in combination with other pharmaceutically active compounds as a suitable set.

The present invention provides a composition for external application for skin for skin regeneration, wrinkle improvement, antioxidant and anti-inflammatory, comprising the compound of formula (I) as an active ingredient.

The composition comprising the compound of the formula (I) of the present invention as an active ingredient can be used in various ways, such as cosmetics and face washes for skin regeneration, wrinkle improvement, antioxidant and anti-inflammatory effects. The products to which the composition can be added include, for example, cosmetics such as various creams, lotions, and skins, and cleansing agents, face washes, soaps, treatments, and cosmetics.

The cosmetic composition of the present invention includes a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingo lipids and seaweed extract.

The water-soluble vitamin may be any compound that can be blended into cosmetics, but preferably vitamin B1, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, vitamin H, etc. In addition, their salts (thiamine hydrochloride, sodium ascorbate salt, etc.) or derivatives (ascorbic acid-2-sodium phosphate salt, ascorbic acid-2-magnesium phosphate salt, etc.) can also be used in the water-soluble vitamins that can be used in the present invention. Is included. The water-soluble vitamin can be obtained by a conventional method such as a microorganism conversion method, a purification method from a culture of microorganisms, an enzyme method, or a chemical synthesis method.

The oil-soluble vitamin may be any compound that can be blended into cosmetics, but preferably vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol), and the like. , Their derivatives (ascorbyl palmitate, ascorbyl stearate, ascorbine dipalmitate, dl-alpha tocopherol acetate, dl-alpha tocopherol acetate nicotine E, DL-pantothenyl alcohol, D-pantothenyl alcohol, pantothenylethyl Ether, etc.) are also included in the oil-soluble vitamin used in the present invention. Oil-soluble vitamins can be obtained by conventional methods such as microbial transformation, microbial culture purification, enzyme or chemical synthesis.

The polymer peptide may be any compound as long as it can be blended into cosmetics, and preferably collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, keratin, and the like. The polymer peptide can be purified by a conventional method such as a purification method from a culture medium of microorganisms, an enzymatic method or a chemical synthesis method, or can be purified and used from natural substances such as dermis such as pigs and cows and silkworm silkworms.

The polymer polysaccharide may be any compound as long as it can be blended into cosmetics. Preferably, hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate, or a salt thereof (sodium salt, etc.) may be mentioned. For example, chondroitin sulfate or a salt thereof can be used after being purified from mammals or fish.

The sphingo lipid may be any compound as long as it can be blended into cosmetics, but preferably, ceramide, phytosphingosine, sphingoglycolipid, and the like. Sphingo lipids are usually purified from mammals, fish, shellfish, yeast or plants by conventional methods or can be obtained by chemical synthesis.

The seaweed extract may be anything as long as it can be blended into cosmetics, but preferably, brown seaweed extract, red seaweed extract, green algae extract, etc., and further, callaginan, arginic acid, sodium arginate purified from these seaweed extracts, Potassium arginate and the like are also included in the seaweed extract used in the present invention. Seaweed extract can be obtained by purification from seaweed by a conventional method.

The cosmetic composition of the present invention may be blended with the above essential ingredients as well as other ingredients normally blended into the cosmetic composition as necessary.

Other ingredients that may be added include fats and oils, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavors, And blood circulation accelerators, cooling agents, limiting agents, and purified water.

Examples of the fats and oils component include ester fats and fats, hydrocarbon fats and fats, silicone fats and fats, fluorine fats, animal fats, and vegetable fats and oils.

Examples of ester oils and fats include tri2-ethylhexanoate glyceryl, 2-ethylhexanoate cetyl, 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 sebacinate, adipine Diisopropyl acid, isoalkyl neopentanoate, tri (caprylic, capric acid) glyceryl, tri2-ethylhexanoate trimethylolpropane, triisostearate trimethylolpropane, tetra2-ethylhexanoate pentaerythritol , Cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, ricinooleic acid , Isostearyl laurate, isotridecyl myristate, isocetyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl oleate, isopropyl isoleate, 2 -Sethostearyl ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol di (caprylic, capric acid), dica Propylene glycol triacrylate, neopentyl glycol dicapric acid, neopentyl glycol dioctanoate, glyceryl tricaprylic acid, glyceryl triundecylate, glyceryl triisopalmitate, glyceryl triisostearate, octyl dodecyl neopentane , Isostearyl octanoate, octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, Octyldecyl stearate, polyglycerin oleic acid ester, polyglycerin isostearic acid ester, triisocetyl citrate, triisoalkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, trityl citrate Ethyl, acetyl triethyl citrate, acetyl tributyl citrate, trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearic acid, di2-ethylhexyl succinate, diisobutyl succinate, diisopropyl sebacate, Dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, phytsteryl isostearate, phytyl oleate, 12-Stealoylhydroxystearate isocetyl, 12-stealoylhydroxystearate stearyl, 12-stealo And ester systems such as isostearyl monohydroxystearate.

Examples of hydrocarbon-based fats and oils include hydrocarbon-based fats and oils such as squalene, liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, and petrolatum.

Examples of silicone oils include polymethylsilicone, methylphenylsilicone, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxanemethylcetyloxysiloxane copolymer, dimethylsiloxanemethylstealoxysiloxane copolymer, and alkyl-modified silicone And oils and amino-modified silicone oils.

Perfluoropolyether etc. are mentioned as a fluorine-type oil and fat.

As animal or vegetable oil, avocado oil, almond oil, olive oil, sesame oil, rice bran oil, new flower oil, soybean oil, corn oil, rapeseed oil, almond oil, palm kernel oil, palm oil, castor oil, sunflower oil, grape seed oil , Cottonseed Oil, Palm Oil, Cucumin Nut Oil, Wheat Germ Oil, Rice Germ Oil, Shea Butter, Moon Seed Colostrum, Marker Demi Nut Oil, Meadow Home Oil, Yolk Yolk Oil, Uji, Horse Oil, Mink Oil, Orange Rape Oil, Jojoba Oil , Candeler wax, carnauba wax, liquid lanolin, hardened castor oil and other animal or plant fats.

Examples of the moisturizing agent include water-soluble low molecular moisturizing agents, oil-soluble molecular moisturizing agents, water-soluble polymers, and fat-soluble polymers.

As a water-soluble low-molecular moisturizer, serine, glutamine, sorbitol, mannitol, sodium pyrrolidone-sodium carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol B (polymerization degree n = 2 or more), polypropylene Glycol (polymerization degree n = 2 or more), polyglycerin B (polymerization degree n = 2 or more), lactic acid, lactate, and the like.

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

Water-soluble polymers include carboxyvinyl polymer, polyasparaginate, tragacanth, xanthan gum, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, water-soluble chitin, chitosan, dextrin, etc. Can be.

Examples of the fat-soluble polymer include polyvinylpyrrolidone ecocene copolymer, polyvinylpyrrolidone hexadecene copolymer, nitrocellulose, dextrin fatty acid ester, and polymer silicone.

Examples of the emollient agent include long-chain acyl glutamate cholesteryl ester, hydroxystearate cholesteryl, 12-hydroxystearic acid, stearic acid, rosin acid, lanolin fatty acid cholesteryl ester, and the like.

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

Examples of the nonionic surfactant 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 sorbit fatty acid ester, and POE. Glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hardened castor oil, POE castor oil, POEPOP (polyoxyethylene polyoxypropylene) copolymer, POEPOP alkyl ether, polyether modified silicone, lauric acid alkanolamide, alkyl And amine oxides and hydrogenated soybean phospholipids.

Examples of the anionic surfactant include fatty acid soap, alpha-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate, alkylamide sulfate, alkyl phosphate, POE alkyl phosphate, and alkylamide phosphate. , Alkyloyl alkyl taurine salts, N-acyl amino acid salts, POE alkyl ether carboxylate salts, alkyl sulfosuccinate salts, sodium alkyl sulfoacetate salts, acylated hydrolyzed collagen peptide salts, perfluoroalkyl phosphate esters, and the like. .

Examples of the cationic surfactant include alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, and chloride. And benzalkonium, diethylaminoethyl stearate, dimethylaminopropylamide stearate, and quaternary ammonium salts of lanolin derivatives.

Examples of the amphoteric surfactant include carboxybetaine type, amidebetaine type, sulfobetaine type, hydroxysulfobetaine type, amidesulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, and amideamine type. And amphoteric surfactants.

Examples of organic and inorganic pigments include silicic acid, silicic anhydride, magnesium silicate, talc, sericite, mica, kaolin, bengala, clay, bentonite, titanium film 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, 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, divinylbenzenestyrene copolymer, silk And organic pigments such as powder, cellulose, CI pigment yellow, and CI pigment orange, and composite pigments of these inorganic pigments and organic pigments.

Examples of the organic powder include metal soaps such as calcium stearate; Alkyl phosphate metal salts such as sodium cetyl acid zinc, lauryl acid zinc, and calcium lauryl acid; Acylamino acid polyvalent metal salts such as N-lauroyl-beta-alanine calcium, N-lauroyl-beta-alanine zinc, and N-lauroylglycine calcium; Amide sulfonic 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-palmitoylazine, N-alpha-paritoylolnitin, N-alpha-lauroylarginine, N-alpha-cured Uji fatty acid acyl arginine -Acyl basic amino acids; N-acylpolypeptides, such as N-lauroylglycylglycine; Alpha-amino fatty acids such as alpha-amino caprylic acid and alpha-amino lauric acid; And polyethylene, polypropylene, nylon, polymethyl methacrylate, polystyrene, divinylbenzenestyrene copolymer, and ethylene tetrafluoride.

Examples of ultraviolet absorbers include paraaminobenzoic acid, ethyl paraaminobenzoate, amyl paraaminobenzoate, octyl paraaminobenzoate, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomentyl salicylate, benzyl cinnamate , Paramethoxy cinnamic acid-2-ethoxyethyl, paramethoxy cinnamic acid octyl, diparamethoxy cinnamic acid mono-2-ethylhexaneglyceryl, paramethoxy cinnamic acid isopropyl, diisopropyl diisopropyl cinnamic acid ester mixture, urocanine Acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and salts thereof, 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-hydr When the like can be mentioned 5-methylphenyl) benzotriazole.

As a fungicide, hinokitiol, triclosan, trichlorohydroxydiphenyl ether, chlorhexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid, zincfilionone, benzalkonium chloride, photosensitive And No. 301, sodium mononitrowire, and undeciric acid.

Examples of antioxidants include butyl hydroxyanisole, propyl gallic acid, and elisoric acid.

Examples of the pH adjusting agent include citric acid, sodium citrate, malic acid, sodium malate, phthalic acid, sodium phthalate, succinic acid, sodium succinate, sodium hydroxide, and sodium monohydrogen phosphate.

Examples of the alcohol include higher alcohols such as cetyl alcohol.

In addition, the compounding component that may be added in addition is not limited to this, and any of the above components can be blended within a range that does not impair the object and effect of the present invention, but is preferably 0.01-5% by weight based on the total weight, More preferably, it is compounded at 0.01-3% weight percentage.

The cosmetic of the present invention may take the form of solutions, emulsions, viscous mixtures, and the like.

The components included in the cosmetic composition of the present invention may include components commonly used in cosmetic compositions in addition to the compounds of the general formula (I) as active ingredients, for example, stabilizers, solubilizers, vitamins, pigments And conventional adjuvants and carriers such as fragrances.

The cosmetic composition of the present invention may be prepared in any formulation conventionally prepared in the art, for example, milk, cream, lotion, pack, foundation, lotion, cosmetic liquid, hair cosmetic, and the like.

Specifically, the cosmetic composition of the present invention is a skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, foundation, essence, nutrition essence, Contains formulations of pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion and body cleanser.

When the formulation of the present invention is a paste, cream or gel, animal fibers, plant fibers, wax, paraffin, starch, tracant, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component. Can be.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in the case of a spray, additionally chlorofluorohydrocarbon, propane / Propellant 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 Fatty acid esters of, 3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol or sorbitan.

When the formulation of the present invention is a suspension, liquid diluents such as water, ethanol or propylene glycol as carrier components, suspensions such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline Cellulose, aluminum metahydroxide, bentonite, agar or trakant, etc. can be used.

When the formulation of the present invention is a surfactant-containing cleansing, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide as a carrier component Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linoline derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

Hereinafter, the present invention will be described in detail by the following examples and experimental examples.

However, the following examples and experimental examples are merely illustrative of the present invention, and the contents of the present invention are not limited by the following examples and experimental examples.

Example 1.

In a two-necked round flask, 10 mmol of the compound of Reaction Scheme 1 (see Table 1) was added at room temperature, and 50 ml of dimethylformamide was added thereto. 12 mmol of potassium carbonate (K2CO3) was added as a catalyst, and then 12 mmol of Bromo methane was slowly added dropwise. After the dropwise addition, the mixture was reacted at room temperature for 4 hours. 500 ml of purified water was added to the reaction mixture and extracted with 100 ml of n-hexane. After drying the hexane layer under reduced pressure, a mixture of n-hexane and ethyl acetate was subjected to silica gel column chromatography as a developing solvent to obtain a temporary reaction product, and identified using a high-speed atomic bombardment mass spectrometry (hereinafter, FAB-MS). Did.

compound X R FAB mass Example 1 O-CH3 CH3 226 [M + H] ⁺ Example 2 O-CH3 C2H5 240 [M + H] ⁺ Example 3 O-CH3 C3H7 254 [M + H] ⁺ Example 4 O-CH3 C4H9 268 [M + H] ⁺ Example 5 O-CH3 C5H11 282 [M + H] ⁺ Example 6 O-CH3 C6H13 296 [M + H] ⁺ Example 7 O-CH3 C8H17 310 [M + H] ⁺ Example 8 O-CH3 C10H21 324 [M + H] ⁺ Example 9 O-CH3 C12H25 338 [M + H] ⁺ Example 10 H C2H5 210 [M + H] ⁺ Example 11 H C8H17 280 [M + H] ⁺ Example 12 H C12H25 294 [M + H] ⁺

Experimental Example 1. Collagen synthesis effect

Compounds prepared according to the methods described in Examples 1 to 12 and vitamin C were added to the culture medium of human-derived fibroblasts to test the effect of promoting collagen synthesis at the cellular level. The measured collagen was quantified using a PICP EIA kit (Procollagen Type I C-peptide enzyme immunoassay kit). Before the experiment, the cytotoxicity of human-derived fibroblasts was evaluated at concentrations of 10ppm, 1ppm, and 0.1ppm, and collagen synthesis ability was evaluated by selecting concentrations without cytotoxicity.

In the experiment, the final concentrations of the compounds were 1 ppm and 10 ppm, and each sample was added to the culture medium of human fibroblasts and cultured for 1 day, and then the culture solution was taken and the degree of collagen synthesis at each concentration was measured using a PICP EIA kit. It was measured at 450nm. In order to compare the effects, collagen synthesis was measured in the same manner for samples in which fibroblast culture medium (control) and vitamin C added with nothing added to a final concentration of 50 ppm were added. The collagen production amount was measured as UV absorbance, and the increase rate of collagen production was calculated as the ratio of collagen production relative to the control group, and the results are summarized in Table 1 below.

Collagen biosynthesis effect (repeated number = 3) sample Concentration (ppm) Collagen growth rate (%) Control (no additives) - - Vitamin C 50 27 Example 1 Compound One 26 10 84 Example 2 Compound One 24 10 81 Example 3 Compound One 27 10 75 Example 4 Compound One 19 10 74 Example 5 Compound One 22 10 67 Example 6 Compound One 16 10 59 Example 7 Compound One 17 10 62 Example 8 Compound One 13 10 51 Example 9 compound One 29 10 76 Example 10 compound One 27 10 79 Example 11 compound One 19 10 67 Example 12 compound One 21 10 51

As can be seen from the results in Table 2, the compounds of Examples 1 to 34 exhibited a better collagen synthesis effect at a lower concentration than when vitamin C, which is generally known to have collagen synthesis ability, was applied.

Experimental Example 2. Antioxidant effect-free radical scavenging rate

Free radical scavenging activity was measured to confirm the antioxidant activity of the compounds prepared according to the methods described in Examples 1 to 12 above. Free radical scavenging activity was measured using DPPH. DPPH was purchased from Sigma and used. First, 1.5 mM standard DPPH ethanol solution was prepared. Then, ethanol was added to the compounds of Examples 1 to 12 and ascorbic acid as antioxidants, respectively, to prepare samples at concentrations of 50 ppm, 25 ppm, 12.5 ppm, 6.25 ppm, and 3.125 ppm. Then, the sample and the standard DPPH solution were added and stirred at the same rate, reacted at 37 ^° C for 30 minutes, and absorbance was measured at 520 nm. At this time, instead of the sample, ethanol was added as a control. The free radical scavenging activity was obtained by obtaining the IC ₅₀ , which is the half maximal inhibitory concentration (inhibition median), and the results are shown in Table 3 below. IC ₅₀ is a general method of expressing free radical scavenging ability as a concentration of ascorbic acid and the compounds of Examples 1 to 12 required to remove 50% of free radicals of the additive-free control group.

Free radical scavenging rate (IC ₅₀ ) sample Free radical elimination rate (ppm) Ascorbic acid 7 Material of Example 1 8 Material of Example 2 9 Material of Example 3 8 Material of Example 4 8 Material of Example 5 9 Materials of Example 6 9 Materials of Example 7 9 Material of Example 8 10 Material of Example 9 8 Material of Example 10 8 Material of Example 11 9 Material of Example 12 9

As shown in Table 3, the compounds of Examples 1 to 12 can confirm the antioxidant effect.

Experimental Example 3. Anti-inflammatory effect-NO production inhibitory effect

In order to confirm the anti-inflammatory effect and the skin trouble-relieving effect of the compounds prepared according to the methods described in Examples 1 to 12, an experiment for inhibiting nitric oxide (NO) formation was performed by the GRISS method using a RAW264.7 cell line. Specifically, RAW264.7 cells, which are macrophages of mice, were passaged several times, placed in 24-well plates to enter 3 to ⁵ wells, and cultured for 24 hours. Subsequently, the compounds of Examples 1 to 12 were diluted to a concentration shown in Table 4 and replaced with a cell medium containing them. The concentration refers to a concentration in which the compound is dissolved in a medium used for evaluation, and it means that 0.01% = 0.1 mg / ml, 0.001% = 0.01 mg / ml. Meanwhile, the NO-producing inhibitor L-NMMA (L-NG-Monomethylarginine) was treated together as a positive control and cultured for 30 minutes, and treated with 1 g of LPS (Lipopolysaccharide) as a stimulator and cultured for 24 hours. 100 l of the supernatant was taken and transferred to a 96-well plate, 100 l of GRIESS solution was added thereto, and the mixture was reacted at room temperature for 10 minutes, and absorbance at 540 nm was measured. The NO inhibitory effect of the compounds of Examples 1 to 12 was compared with the negative control group treated only with LPS and no NO inhibitor, and the results are shown in Table 4 below.

NO production suppression effect sample density(%) NO generation inhibition rate (%) L-NMMA 0.001 38.6 Example 1 Compound 0.01 56.7 0.001 15.7 Example 2 Compound 0.01 49.7 0.001 13.4 Example 3 Compound 0.01 48.4 0.001 12.7 Example 4 Compound 0.01 39.8 0.001 11.8 Example 5 Compound 0.01 41.2 0.001 9.8 Example 6 Compound 0.01 38.9 0.001 7.6 Example 7 Compound 0.01 29.7 0.001 5.8 Example 8 Compound 0.01 26.8 0.001 6.2 Example 9 compound 0.01 49.8 0.001 16.2 Example 10 compound 0.01 39.8 0.001 14.8 Example 11 compound 0.01 38.9 0.001 14.8 Example 12 compound 0.01 41.2 0.001 14.8

Production Example 1. Preparation of flexible cosmetic water

Formulation 1 and Comparative Formulation 1 were prepared with the composition of Table 5 below.

Composition (% by weight) Formulation 1 Comparative Formulation 1 a b c d Material of Example 2 0.5 - - - - Material of Example 8 - 0.5 - - - Material of Example 11 - - 0.5 - - Material of Example 12 - - - 0.5 - ethanol 10.0 10.0 10.0 10.0 10.0 Polyoxyethylene cured castor oil  1.0  1.0  1.0  1.0  1.0 Methyl paraoxybenzoate  0.2  0.2  0.2  0.2  0.2 glycerin  5.0  5.0  5.0  5.0  5.0 1,3-butylene glycol  6.0  6.0  6.0  6.0  6.0 incense Proper Proper Proper Proper Proper Purified water to 100 to 100 to 100 to 100 to 100

Production Example 2. Preparation of nutrient makeup

Formulation 2 and Comparative Formulation 2 were prepared with the composition of Table 6 below.

Composition (% by weight) Formulation 2 Comparative Formulation 2 a b c d Material of Example 2 0.5 - - - - Material of Example 8 - 0.5 - - - Material of Example 11 - - 0.5 - - Material of Example 12 - - - 0.5 - Polyoxyethylene cured castor oil 1.0 1.0 1.0 1.0 1.0 Methyl paraoxybenzoate 0.2 0.2 0.2 0.2 0.2 glycerin 6.0 6.0 6.0 6.0 6.0 1,3-butylene glycol 5.0 5.0 5.0 5.0 5.0 Carbomer 0.2 0.2 0.2 0.2 0.2 Triethanolamine 0.3 0.3 0.3 0.3 0.3 Propylene glycol 5.0 5.0 5.0 5.0 5.0 ethanol 3.2 3.2 3.2 3.2 3.2 Carboxyvinyl polymer 0.1 0.1 0.1 0.1 0.1 incense Proper Proper Proper Proper Proper Purified water to 100 to 100 to 100 to 100 to 100

Preparation Example 3. Preparation of cream

Formulation 3 and Comparative Formulation 3 were prepared with the composition of Table 7.

Composition (% by weight) Formulation 3 Comparative Formulation 3 a b c d Material of Example 2 0.5 - - - - Material of Example 8 - 0.5 - - - Material of Example 11 - - 0.5 - - Material of Example 12 - - - 0.5 - Cetane 2.0 2.0 2.0 2.0 2.0 PAGE-20 1.0 1.0 1.0 1.0 1.0 Sorbitan monostearate 1.0 1.0 1.0 1.0 1.0 Mineral oil 10.0 10.0 10.0 10.0 10.0 Trioctanoate 5.0 5.0 5.0 5.0 5.0 Triethanolamine 0.5 0.5 0.5 0.5 0.5 Carbomer 0.2 0.2 0.2 0.2 0.2 glycerin 5.0 5.0 5.0 5.0 5.0 Propylene glycol 3.0 3.0 3.0 3.0 3.0 antiseptic Proper Proper Proper Proper Proper incense Proper Proper Proper Proper Proper Purified water to 100 to 100 to 100 to 100 to 100

Preparation Example 4. Preparation of ointment for external use on skin

Formulation 4 and Comparative Formulation 4 were prepared with the composition of Table 8.

Composition (% by weight) Formulation 4 Comparative Formulation 4 a b c d Material of Example 2 0.5 - - - - Material of Example 8 - 0.5 - - - Material of Example 11 - - 0.5 - - Material of Example 12 - - - 0.5 - Diethyl sebacate 8.0 8.0 8.0 8.0 8.0 Arrears 5.0 5.0 5.0 5.0 5.0 Polyoxyethylene oleyl ether phosphate 6.0 6.0 6.0 6.0 6.0 Sodium benzoate Proper Proper Proper Proper Proper vaseline to 100 to 100 to 100 to 100 to 100

Production Example 5. Preparation of essence

Formulation 5 and Comparative Formulation 5 were prepared with the composition of Table 9 below.

Composition (% by weight) Formulation 5 Comparative Formulation 5 a b c d Material of Example 2 0.5 - - - - Material of Example 8 - 0.5 - - - Material of Example 11 - - 0.5 - - Material of Example 12 - - - 0.5 - Propylene glycol 10.0 10.0 10.0 10.0 10.0 glycerin 10.0 10.0 10.0 10.0 10.0 Sodium hyaluronate aqueous solution (1%) 5.0 5.0 5.0 5.0 5.0 ethanol 5.0 5.0 5.0 5.0 5.0 Polyoxyethylene cured castor oil 1.0 1.0 1.0 1.0 1.0 Methyl paraoxybenzoate 0.1 0.1 0.1 0.1 0.1 Carbomer 0.4 0.4 0.4 0.4 0.4 incense Proper Proper Proper Proper Proper Purified water to 100 to 100 to 100 to 100 to 100

Production Example 6. Preparation of pack

Formulation 6 and Comparative Formulation 6 were prepared with the composition of Table 10 below.

Composition (% by weight) Formulation 6 Comparative Formulation 6 a b c d Material of Example 2 0.5 - - - - Material of Example 8 - 0.5 - - - Material of Example 11 - - 0.5 - - Material of Example 12 - - - 0.5 - glycerin 5.0 5.0 5.0 5.0 5.0 Propylene glycol 4.0 4.0 4.0 4.0 4.0 Polyvinyl alcohol 15.0 15.0 15.0 15.0 15.0 ethanol 8.0 8.0 8.0 8.0 8.0 Polyoxyethylene cured castor oil 1.0 1.0 1.0 1.0 1.0 Polyoxyethylene oleyl ether phosphate 1.0 1.0 1.0 1.0 1.0 Methyl paraoxybenzoate 0.2 0.2 0.2 0.2 0.2 incense Proper Proper Proper Proper Proper Purified water to 100 to 100 to 100 to 100 to 100

Claims (1)

A composition for improving skin comprising a derivative of the compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof as an active ingredient:
(I)

In the above formula, X is hydrogen or methoxy, and R is a C1 to C20 linear or branched alkyl group.