KR101313178B1 - Composition for skin-whitening including phenolic compound isolated from extracts of dendropanax morbifera - Google Patents

Abstract

The present invention is to provide a skin whitening cosmetic composition and an external skin pharmaceutical composition containing a phenolic compound and its pharmaceutically acceptable salts isolated from the Hwangchil wood extract as an active ingredient.

Description

Skin Whitening Composition Containing Phenolic Compounds Isolated from Hwangchil Tree Extracts {COMPOSITION FOR SKIN-WHITENING INCLUDING PHENOLIC COMPOUND ISOLATED FROM EXTRACTS OF DENDROPANAX MORBIFERA}

The present invention relates to a new phenolic compound isolated from the Hwangchil tree extract and a composition containing the same. Specifically, the present invention relates to a cosmetic composition for skin whitening and a cosmetic composition for external skin containing a phenolic compound isolated from the Hwangchil tree extract.

Hwangchil tree (Dendropanax morbifera) belongs to the family Elmaceae. It is an evergreen broad-leaved arboreous tree native to Korea's Chonnam coastal region and Jeju Island. When the bark is wound, yellow sap comes out and it is called Hwangchil-tree. Yellow sap is used as a paint.

The main component of Hwangchil-tree is essential oil, and it is composed of light yellow thick liquid. The efficacy of Hwangchil-tree, blood circulation improvement, liver function improvement, antioxidant activity, immunity enhancement, neurostable, antibacterial action and anti-cancer activity is known. There is no active research on the use of Hwangchil trees in skin-related diseases. In addition, the research on the sap of Hwangchil-tree and the compounds isolated from extracts are limited to terpenoid essential oil components.

 Meanwhile, melanocytes present in the basal epidermal layer of human skin are stimulated by ultraviolet rays, radiation, and the like to activate tyrosinase, which is converted into dopa and dopaquinone. Dopachrome (dopachrome) is finally produced black and brown melanin. The melanin biosynthesis process has recently been intensively studied, and the findings have been applied to therapeutic and whitening products using various melanin inhibitors.

In addition, research is being actively conducted through ingredients obtained from natural resources. However, since little is known about the components of the Hwangchil-tree extract, research is needed to find useful ingredients for skin whitening from Hwangchil-tree extract.

The present inventors have conducted a study on the skin whitening ingredient possessed by Hwangchil wood. As a result, it was found that the Hwangchil-tree extract exhibits a potent melanogenesis inhibitory effect, thus completing the present invention.

 An object of the present invention is to provide a cosmetic composition for skin whitening containing a compound isolated from the Hwangchil wood extract.

Another object of the present invention is to provide an external skin pharmaceutical composition having a skin lightening activity containing a compound isolated from the extract of the Hwangchil-tree.

Another object of the present invention is to provide a new compound isolated from the Hwangchil wood extract.

The present invention provides a cosmetic composition for skin whitening containing a phenolic compound and its pharmaceutically acceptable salts isolated from the Hwangchil wood extract as an active ingredient.

In another aspect, the present invention provides a pharmaceutical composition for external skin having a skin lightening activity containing a phenolic compound and its pharmaceutically acceptable salts as an active ingredient isolated from the Hwangchil wood extract.

The phenolic compound is a glucopyranoside-based polyether phenol compound, and may be (+)-syringaresinol-OBD-glucopyranoside represented by Formula 1 below:

[Formula 1]

The composition of the present invention can inhibit melanin production by containing a derivative of the compound represented by the above formula according to the present invention and a pharmaceutically acceptable salt thereof.

Specifically, the phenolic compound of the formula according to the present invention shows an excellent inhibitory effect when compared with kojic acid, arbutin and the like used as a melanin production inhibitor. Therefore, the compound of the formula of the present invention can be used as a melanin production inhibitor, that is, a cosmetic composition for skin whitening.

The phenolic compound may include 0.001 to 30% by weight of the compound based on the total weight of the composition.

The cosmetic composition, skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutrition cream, moisturizing cream, hand cream, foundation, essence, nutrition essence, pack, soap, The formulation may be selected from the group consisting of cleansing foam, cleansing lotion, cleansing cream, body lotion and body cleanser, but is not necessarily limited thereto.

The pharmaceutical composition may be selected from the group consisting of creams, gels, patches, sprays, ointments, warnings, lotions, linen, pasta and cataplasma, but is not necessarily limited thereto.

The hwangchil tree extract may be extracted from the stems, seeds, leaves, roots of the hwangchil tree.

The hwangchil wood extract is preferably obtained by extracting the hwangchil wood with an aqueous alcohol solution or water bath extraction. The hwangchil wood can be used without limitation, such as cultivated or commercially available.

The method of preparing the Hwangchil-tree extract may be a conventional extraction method in the art, such as ultrasonic extraction, filtration, reflux extraction. Specific examples are as follows.

First, the dry powder of Hwangchil wood was prepared as a soluble extract using a nonpolar solvent (step 1);

The soluble extract prepared in step 1 was fractionated, dried, and concentrated under pressure to prepare a concentrate (step 2); And

The concentrate prepared in step 2 is separated and purified by chromatography to obtain a phenolic compound (step 3).

The nonpolar solvent of step 1 is any solvent that can be generally used in the art. Can be used. For example, it can be selected from the group consisting of water, anhydrous or lower alcohol having 1 to 4 carbon atoms, acetone, ethyl acetate, butyl acetate and 1,3-butylene glycol. Preferably ethanol, most preferably 80% ethanol. The extraction solvent can be added to extract for 10 hours to 3 days at 20 ~ 30 ℃.

Step 2 is a step of concentrating the extract obtained in step 1 by systematic fractionation, drying and concentration under reduced pressure. The soluble extract obtained in step 1 was subjected to a systematic fraction using a separatory funnel to fractionate the ethyl acetate layer and the water layer, and the fractionated water layer was partitioned into an n-butanol layer and a water layer. The fractionated ethyl acetate layer, n-butanol layer, and water layer are washed with unsaturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a concentrate.

Step 3 is a step of obtaining a phenolic compound of Chemical Formula 1 by separating and purifying the concentrate prepared in Step 2 by chromatography.

The n-butanol concentrate was loaded on a chromatography packed with silica gel with the concentrate obtained in step 2, and then developed with chloroform (100% (w / v)), followed by chloroform: methanol mixed solvent 49: 1, 19: 1, 9: 1, 4: 1, 1: 1 can be used as a mixed solvent in a volume ratio, and the fraction eluted by the 19: 1 mixed solvent can be concentrated. The concentrate was subjected to reverse phase silica gel column chromatography with a mixed solvent ratio of methanol to water of 1: 1, and purified using Sephadex LH-20 to obtain the compound of Formula 1.

In another aspect, the present invention provides a composition containing a phenolic compound or a pharmaceutically acceptable salt thereof obtained from the Hwangchil wood extract as an active ingredient.

The salt may be an acid addition salt formed by pharmaceutically acceptable free acid. Thus, the compounds may be formed with pharmaceutically acceptable acid addition salts according to methods conventional in the art. Inorganic and organic acids can be used as the free acid, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, etc. can be used as the inorganic acid, citric acid, acetic acid, lactic acid, maleic acid, fumaric acid, gluconic acid, methanesulfuric acid. Phonic acid, acetic acid, glyconic acid, succinic acid, tartaric acid, 4-toluenesulfonic acid, galluxuronic acid, embonic acid, glutamic acid or aspartic acid, and the like can be used. Preferably, hydrochloric acid may be used as the inorganic acid, and methanesulfonic acid may be used as the organic acid. In addition, the compounds according to the present invention may include not only pharmaceutically acceptable salts, but also all salts, hydrates, and solvates which can be prepared by conventional methods.

In the present invention, the term "active ingredient" means a substance or a group of substances (a medicinal agent, etc., for which a pharmacologically active ingredient is not known, which is expected to express specific effects or effects directly or indirectly in the pharmacological action inherent in this ingredient). It includes).

In the cosmetic composition for skin whitening of the present invention, Hwangchil wood has been used for a long time as a herbal medicine and food. Hwangchil-tree extract of the present invention extracted from them and the compounds isolated therefrom also have no problems such as toxicity and side effects.

The cosmetic composition may be used in various ways, such as cosmetics and shampoos for the skin whitening effect. Examples of products to which the present composition can be added include cosmetics such as various creams, lotions, skins, essences, shampoos, rinses, cleansing agents, face washes, soaps, treatments, packs, and essences. The cosmetic of the present invention may include a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids and seaweed extract.

The water-soluble vitamin is not particularly limited as long as it can be compounded in cosmetics. Preferably, vitamin B, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, And their salts (thiamine hydrochloride, sodium ascorbate, etc.) or derivatives (sodium ascorbic acid-2-phosphate, magnesium ascorbate-2-phosphate etc.) can also be added to water-soluble vitamins . The water-soluble vitamin can be obtained by a conventional method such as a microorganism conversion method, a purification method from a culture of a microorganism, an enzymatic method, or a chemical synthesis method.

The oil-soluble vitamin may be any compound that can be incorporated 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. , Derivatives thereof (ascorbic palmitate, ascorbic stearate, ascorbic acid dipalmitate, dl-alpha tocopherol acetate, dl-alpha tocopherolvitamin E, DL-pantotenyl alcohol, D-pantothenyl alcohol, pantothenyl ethyl) Ethers, etc.) are also included in the oil-soluble vitamins used in the present invention. Usability Vitamins can be obtained by a conventional method such as a microorganism conversion method, a purification method from a culture of a microorganism, an enzyme or a chemical synthesis method.

The polymeric peptide may be any compound as long as it can be compounded in cosmetics, and examples thereof include collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, and keratin. The polymeric peptide can be obtained by a conventional method such as purification from a culture broth of a microorganism, an enzymatic method, or a chemical synthesis method, or it can be purified from natural products such as ducks such as pigs and cows and silk fiber of silkworms.

The polymeric polysaccharide may be any compound as long as it can be incorporated in cosmetics, and examples thereof include hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate or a salt thereof (sodium salt, etc.). For example, chondroitin sulfate or a salt thereof can be usually purified from mammals or fish.

Sphingo lipids may be any as long as they can be incorporated into cosmetics, and preferable examples thereof include ceramides, phytosphingosine and sphingoglycolipids. Sphingoid lipids can be purified from ordinary mammals, fish, shellfish, yeast or plants by conventional methods or can be obtained by chemical synthesis.

The seaweed extract may be any of those which can be compounded in cosmetics. Preferably, the seaweed extract is selected from the group consisting of algae extract, red pepper extract, green algae extract and the like. Also, the algae extract may be colored guanine, arginic acid, Potassium alginate and the like are also included in the seaweed extract used in the present invention. Seaweed extract can be obtained from seaweed by a conventional method.

The cosmetic of the present invention may be blended with other essential ingredients, if necessary, in combination with the essential ingredients.

Other components 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, flavorings, Blood circulation accelerators, cooling agents, restriction agents, purified water and the like.

Examples of the oil retaining component include ester-based oil retaining, hydrocarbon-based oil retaining, silicone-based oil retaining, fluoric oil retaining, animal retention and plant retention.

Examples of the hydrocarbon-based oils and fats include hydrocarbon oils such as squalene, liquid paraffin, alpha-olefin oligomers, isoparaffins, ceresin, paraffins, liquid isoparaffins, polybutenes, microcrystalline waxes, and vaseline.

Examples of silicone based oils include polymethyl silicone, methylphenyl silicone, methyl cyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane-methylcetyloxysiloxane copolymer, dimethylsiloxane-methylstarchoxysiloxane copolymer, alkyl Modified silicone oils, and amino-modified silicone oils.

Examples of the fluorine-based oil include perfluoropolyether and the like.

Examples of animal or vegetable oils include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, new flower oil, soybean oil, corn oil, rape oil, apricot kernel oil, palm kernel oil, palm oil, castor oil, , Corn oil, palm oil, palm oil, cucumber nut oil, wheat germ oil, rice germ oil, shea butter, coltsfoot colostrum, marker daisy nut oil, mead home oil, egg oil, , Canned wax, carnauba wax, liquid lanolin, hardened castor oil, and the like.

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

Examples of the water-soluble low-molecular moisturizing agent include serine, glutamine, sorbitol, mannitol, sodium pyrrolidone-carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol B Glycol (polymerization degree n = 2 or more), polyglycerin B (polymerization degree n = 2 or more), lactic acid, lactic acid salt and the like.

Examples of the lipid-soluble low-molecular moisturizing agent include cholesterol and cholesterol ester.

Examples of the water-soluble polymer include carboxyvinyl polymer, polyaspartic acid, tragacanth, xanthan gum, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, water-soluble chitin, chitosan, dextrin, etc. .

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

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

Examples of nonionic surfactants are self-emulsifying glycerin monostearate, propylene glycol fatty acid esters, glycerin fatty acid esters, polyglycerol fatty acid esters, sorbitan fatty acid esters, POE (polyoxyethylene) sorbitan fatty acid esters, POE sorbitan fatty acid esters, and POE. Glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hardened castor oil, POE castor oil, POE / POP (polyoxyethylene / polyoxypropylene) copolymer, POE / POP alkyl ether, polyether modified silicone, lauric acid Alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid, etc. are mentioned.

Examples of the anionic surfactant include fatty acid soap, alpha-acylsulfonate, alkylsulfonate, alkylallylsulfonate, alkylnaphthalenesulfonate, alkylsulfate, POE alkylether sulfate, alkylamide sulfate, alkyl phosphate, POE alkyl phosphate, alkylamide phosphate , Alkyloyl taurine salts, N-acyl amino acid salts, POE alkyl ether carboxylates, alkylsulfosuccinates, sodium alkylsulfoacetates, acylated hydrolyzed collagen peptide salts, and perfluoroalkyl phosphate esters .

As cationic surfactant, alkyl trimethylammonium chloride, stearyl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride, cetostearyl trimethyl ammonium chloride, distearyl dimethyl ammonium chloride, stearyl dimethyl benzyl ammonium bromide, behenyl trimethyl ammonium chloride, chloride Benzalkonium, diethylaminoethyl stearate, dimethylaminopropyl stearate, lanolin derivatives, quaternary ammonium salts, and the like.

Examples of the amphoteric surfactant include carboxybetaine type, amide betaine type, sulfobetaine type, hydroxysulfobetaine type, amidosulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type and amide amine type Amphoteric surfactants and the like.

Examples of the organic and inorganic pigments include inorganic pigments such as silicic acid, silicic anhydride, magnesium silicate, talc, sericite, mica, kaolin, Bengala, clay, bentonite, titanium mica, titanium oxide, bismuth chloride, zirconium oxide, magnesium oxide, Inorganic pigments such as calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, chromium oxide, chromium oxide, chromium hydroxide, But are not limited to, polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin, fluororesin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, Silk powder, cellulose, CI Pigment Yellow, CI Pigment Orange, and composite pigments of inorganic pigments and organic pigments thereof.

As the organic powder, metallic soap such as calcium stearate; Metal salts of alkyl phosphates such as sodium zinc cetylate, zinc laurylate and calcium lauryl laurate; Acylamino acid valent metal salts such as -lauroyl-beta-alanine calcium, N-lauroyl-beta-alanine zinc, and N-lauroylglycine calcium; Amidosulfonic acid multivalent metal salts such as N-lauroyl-taurine calcium and N-palmitoyl-taurine calcium; Such as N-epsilon-lauroyl-L-lysine, N-epsilon-palmitoylidene, N-alpha-paratyylnitine, N-alpha-lauroyl arginine, Acyl basic amino acids; N-acylpolypeptides such as N-lauroylglycylglycine; Alpha-amino fatty acids such as alpha-aminocaprylic acid, alpha-aminoaurauric acid, and the like; Polyethylene, polypropylene, nylon, polymethylmethacrylate, polystyrene, divinylbenzene-styrene copolymer, ethylene tetrafluoride, and the like.

Examples of the disinfectant include hinokitiol, trichloroacid, trichlorohydroxydiphenyl ether, crohexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid, zinc filitione, benzalkonium chloride, No. 301, mononitro and eicol sodium, and undecylenic acid.

Examples of the antioxidant include butylhydroxyanisole, gallic acid propyl, and eicosorbic acid.

Examples of the pH adjuster include citric acid, sodium citrate, malic acid, sodium malate, fumaric acid, sodium fumarate, succinic acid, sodium succinate, sodium hydroxide, sodium monohydrogenphosphate and the like.

As alcohol, higher alcohols, such as cetyl alcohol, are mentioned.

In addition, the compounding component which may be added other than this is not limited to this, Moreover, Although all said components can be mix | blended within the range which does not impair the objective and effect of this invention, Preferably it is 0.01-5% weight percentage with respect to a total weight, More preferably 0.01-3% by weight.

The cosmetic of the present invention may take the form of a solution, an emulsion, a viscous mixture or the like.

The components included in the cosmetic composition of the present invention may include components conventionally used in cosmetic compositions in addition to the compounds isolated from the Hwangchil tree extract as active ingredients, for example, stabilizers, solubilizers, vitamins, pigments and flavorings. Conventional adjuvants and carriers such as;

The cosmetic composition for skin whitening of the present invention may be prepared in any formulation conventionally prepared in the art, and includes, for example, emulsion, cream, lotion, pack, foundation, lotion, essence, hair cosmetic, and the like.

Specifically, the cosmetic composition of the present invention skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutrition cream, moisturizing cream, hand cream, foundation, essence, nutrition essence, Formulations of packs, soaps, cleansing foams, cleansing lotions, cleansing creams, hair lotions, hair tonics, hair essences, hair shampoos, hair rinses, hair treatments, body lotions and body cleansers.

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

In the case where 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. Especially, in the case of a spray, a mixture of chlorofluorohydrocarbons, propane / Propane or dimethyl ether.

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

When the formulation of the invention is a suspension, liquid carrier diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline Cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

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

In the present invention, the external skin pharmaceutical composition may further include a suitable carrier, excipient and diluent commonly used in the manufacture of a pharmaceutical composition.

In addition, the external skin pharmaceutical composition may be used in the form of external preparations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and sterile injectable solutions in accordance with conventional methods, preferably, Cream, gel, patch, spray, ointment, warning, lotion, lining, pasta or cataplasma formulations.

Carriers, excipients and diluents that may be included in the composition include lactose, dextrose, sucrose, oligosaccharides, 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. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

In addition, the preferred dosage of the pharmaceutical composition depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the preferred effect, the composition of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 10 mg / kg per day. Topical administration may be administered once a day or may be divided several times. The dose is not intended to limit the scope of the invention in any way.

When the new phenolic compound isolated from the extract of Hwangchil-tree of the present invention is used as a cosmetic composition for skin whitening and a pharmaceutical composition for external skin, melanin production is inhibited.

1 is a graph measured by 1 H-NMR of a compound of the formula of an embodiment according to the present invention.
2 is a graph measured by 13 C-NMR of a compound of formula of one embodiment according to the present invention.
Figure 3 is a graph measured by heteronuclear multiple bond correlation (HMBC) of the compound of the formula of one embodiment according to the present invention.
Figure 4 is a graph showing the results of the evaluation of melanin inhibitory activity in Melan-A cells of the Hwangchil wood fraction (Fr.-5-1 ~ 4) according to the present invention.
5 is a graph showing the results of the evaluation of melanin inhibitory activity in Melan-A cells of the Hwangchil wood fraction (Fr.-5-4-1-4) according to the present invention.

Hereinafter, preferred examples are provided to aid the understanding of the present invention, but the following examples are merely illustrative of the present invention, and various changes and modifications can be made within the scope and spirit of the present invention. It is obvious to the skilled person, and it is natural that such variations and modifications fall within the scope of the appended claims.

Example  1: Hwangchil Tree Extract Manufacturer

In order to prepare the ethanol extract of Hwangchil, Hwangchil (Dendropanax morbifera) (Gwangju, Jeollanam-do) was used. After drying 10kg of the yellow lacquer tree leaves in the shade and cutting it, extraction was performed while stirring with a magnetic stirrer for 3 days at room temperature using 80% ethanol to obtain an extract of the yellow lacquer tree. The obtained extract was filtered and concentrated using a vacuum concentrator at 40 ℃. 590 g of the resulting gum mass was suspended in water and partitioned successively with ethyl acetate and n-butanol.

Example  2: Preparation of the Compound from the Sacred Tree Ethanol Extract

2-1: Extraction and Separation from Ethanol Extract of Sacred Tree

The ethyl acetate layer, n-butanol layer, and water layer of the sulfuric acid ethanol extract of Example 1 were concentrated using a vacuum concentrator. The n-butanol layer concentrate (120 g) was injected into a column chromatography packed with silica gel (230-400 mesh, Merck), followed by 3 L of chloroform, followed by 49: 1 (10 L), 19: 1 (chloroform: methanol). 15r), 9: 1 (15L), 4: 1 (10L), and 1: 1 (5L) were sequentially eluted in the developing solvent to concentrate Fr.-5, the fifth fraction of the eluted fraction.

The concentrated Fr.-5 was subjected to column chromatography packed with silica gel (230-400 mesh, Merck) using n-hexane: acetone (19: 1 to 1: 1) as a mobile phase, and n-hexane: In the case of acetone (1: 1), the fourth fraction of the eluted fraction, Fr.-5-4, was concentrated.

The concentrated Fr.-5-4 was subjected to column chromatography packed with reverse phase silica gel (ODS-A, RP-18) using methanol: water (2: 1) as a mobile phase, followed by filling with Sephadex LH-20. Purification was carried out by column chromatography to obtain the compound (54 mg) as a double white solid.

2-2: Identification of Glycoside Compounds

The compound obtained in Example 2-1 was determined using a VG high resolution GC / MS spectrometer, Election Ionization MS, Autospec-Ultima, and the molecular weight and molecular formula were determined, and nuclear magnetic resonance analysis (Bruker AMX). 500) through 1H-NMR, 13C-NMR, HOMO-COSY, 1H-Detected heteronuclear Multiple-Quantum Coherence (HMQC), Thermotron Multiple-Bond Correlation (HMBC), Distortionless Enhancement by Polarization (DEPT) 1 to 3, and based on these data, reported data (Hyun Bong park; Kyu Ha Lee; ki kyun Lee; Il Kyen Lee; Hyung Tun Noh; Sang Un Choi; Kang Ro Lee Lignans from the Roots of Berberis amurensis Natural product Sciences 2009, 15 (1), 17-21) to determine the molecular structure of the compound.

The measurement results are shown in the following Chemical Formula 1, and the compound of the formula was identified as (+)-syringaresinol-OBD-glucopyranoside:

[Formula 1]

1) White powder solid

2) ESI-MS: m / z 580 [M < + >] (calcd. For C28H36O13: 580.5776)

3) ¹ H-NMR (400 MHz, pyridine-d 5 ) 6.96 (2H, s, H-2, H-6), 6.93 (2H, s, H-2 ', H-6'), 5.74 (1H , d, J = 6.4 Hz, H-1 ”), 4.97 (1H, d, J = 4.0 Hz, H-2), 4.93 (1H, d, J = 5.2 Hz, H-6), 4.39 (2H, dd, J = 14.1, 4.0 Hz, H-4b, H-7b), 4.31 (2H, dd, J = 9.0, 3.0 Hz, H-4a, H-7a), 3.83 (6H, s, 3, 5- OCH ₃ ), 3.80 (6H, s, 3 ', 5'-OCH ₃ ), 4.38-4.26 (2H, m, H-6 ”a, H-6” b), 3.49 (1H, m, H-2 ”), 4.06 (2H, m, H-3”, H-4 ”), 3.92 (1H, m, H-5”), 3.22 (2H, br m, H-1, H-5).

4) ¹³ C-NMR (100 MHz, pyridine-d 5 ) 154.1 (C-3, 5), 149.4 (C-3 ', 5'), 138.5 (C-1), 137.5 (C-4 '), 135.7 (C-4), 132.2 (C-1 '), 105.2 (C-1 ”), 105.0 (C-2, 6), 104.7 (C-2', 6 '), 86.6 (C-7') , 86.4 (C-7), 78.7 (C-5 ”), 78.4 (C-3”), 76.1 (C-2 ”), 72.3 (C-9), 72.2 (C-9 '), 71.8 (C -4 ”), 62.8 (C-6”), 56.8 (C-3 ', 5'-OCH ₃ ), 56.6 (C-3, 5-OCH ₃ ), 55.0 (C-8'), 54.9 (C -8).

Example  3: Determination of the Melanin Inhibitory Activity of the Extract of Hwangchil Tree

The melanin inhibitory activity of Hwangchil-tree extract or phenolic compounds isolated therefrom was investigated.

In order to determine the melanin inhibitory activity of the ethanol extract of Hilchi chinensis of the present invention, the whitening effect was measured using melan-A. Representative melan-A among the melanin inhibitory activity cells was used, but is not limited thereto.

Melan-A cells, an immortalized cell line derived from C57BL / 6 mice, Used by Bennett (Cancer Research Center, London, England). Melan-A cells were 10% FBS, 200 nM 12-O-tetradecanoylphorbol-13-acetate, 100 mg / L of streptomycin, 100 IU / Cultured under 37 ° C., 10% CO ₂ conditions using RPMI 1640 medium containing ml of penicillin.

If Melan-A cells grow confluent in the incubator, remove the cells with 0.25% trypsin / EDTA, inject 1x105 cells per well into a 24-well plate, wait 24 hours for the cells to adhere well to the plate and wash once with PBS. Thereafter, the cells were treated by adding the sample material of Example 2 (first to fourth fractions of Fr.-5) to the culture medium containing no FBS. The sample material was dissolved in DMSO to 1000 times the desired concentration, and then diluted to 1/1000 when used in the cell. As a control, N-phenylthiourea (PTU) was used, and a solution in which DMSO was treated at the same concentration as the sample was used. After treating the sample material for 3 days as described above, the amount of melanin was dissolved in a solution containing 10% DMSO in 1N NaOH and absorbance was measured at 490 nm. The cell lysate was obtained again by the Bradford method and expressed as the amount of melanin per protein.

As a result, it was confirmed that the Fr.-5 fraction, which was evaluated as having an excellent melanin production inhibitory effect, showed melanin production inhibitory activity better than that of the control group 1-phenyl-2-thiourea.

Subsequently, four fractions (Fr.-5-1 to 4) were obtained by performing open column chromatography on the Fructus Fr.-5 fraction, which was evaluated as having an excellent melanin inhibitory effect.

As a result, as shown in Figure 4, it was confirmed that the Fr.-5-4 fraction, which was evaluated as having an excellent melanin production inhibitory effect, showed melanin production inhibitory activity better than the control group N-phenylthiourea.

In addition, four fractions (Fr.-5-4-1 to 4) were subjected to open column chromatography on the Fructus Fr.-5-4 fraction, which was evaluated as having an excellent melanin inhibitory effect. ) As a result, as shown in Figure 5, it was confirmed that the Fr.-5-4-3 fraction exhibited better melanin production inhibitory activity than the control group N-phenylthiourea.

Formulation example  1: Preparation of Soft Cosmetics

The preparation example of the flexible longevity containing the compound of Example 2-1 is as Table 1 below.

[Table 1]

Formulation example  2: External skin preparation  Produce

Preparation examples of the external preparation for skin containing the compound of Example 2-1 are as shown in Table 2 below.

[Table 2]

Simple modifications or changes of the present invention can be easily carried out by those skilled in the art, and all such modifications or changes can be seen to be included in the scope of the present invention.

Claims (7)

A cosmetic composition for skin whitening containing (+)-syringaresinol-OBD-glucopyranoside and its pharmaceutically acceptable salt thereof represented by the following Chemical Formula 1 as an active ingredient isolated from the Hwangchil tree extract.

[Formula 1]

An external skin pharmaceutical composition having a skin whitening activity containing (+)-syringaresinol-OBD-glucopyranoside and its pharmaceutically acceptable salt thereof represented by the following Chemical Formula 1 as an active ingredient.

[Formula 1]

delete The composition of claim 1 or 2, wherein the (+)-syringaresinol-OBD-glucopyranoside comprises 0.001 to 30% by weight relative to the total weight of the composition.
According to claim 1, wherein the composition is a skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutrition cream, moisturizing cream, hand cream, foundation, essence, nutrition essence, And a formulation selected from the group consisting of a pack, a soap, a cleansing foam, a cleansing lotion, a cleansing cream, a body lotion and a body cleanser.
The composition of claim 2, wherein the composition has a formulation selected from the group consisting of creams, gels, patches, sprays, ointments, warnings, lotions, linings, pastas and cataplasmas.
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