KR20110138929A - Composition for inhibition skin-aging comprising of bis3,5-dimethoxychalcone - Google Patents

Abstract

PURPOSE: An anti-aging inhibitor compound containing bis 3,5-dimethoxychalcone is provided to control the expression of an MMP-9 gene, and to suppress the decomposition of collagen. CONSTITUTION: An anti-aging inhibitor compound contains bis 3,5-dimethoxychalcone marked with chemical formula 1. The anti-aging inhibitor compound controls the gene expression of matrix metalloproteinase-9 induced from a tumor necrosis factor-alpha for suppressing the decomposition of collagen. The compound is used as a skin aging resister.

Description

Skin aging inhibitor composition containing bis-3-5-dimethoxychalcone {COMPOSITION FOR INHIBITION SKIN-AGING COMPRISING OF BIS3,5-DIMETHOXYCHALCONE}

The present invention relates to a skin aging inhibitor composition comprising a bis3,5-dimethoxychalcone compound represented by the following formula (1), and more particularly tumor necrosis factor-α By inhibiting the gene expression of Matrix Metalloproteinase-9 (MMP-9) induced by α; TNF-α), it inhibits the degradation of collagen, a component of skin, and improves skin aging. The present invention relates to a composition for preventing skin aging and improving wrinkles, which may include the bis3,5-dimethoxychalcone compound of Formula 1, which may be prevented.

Skin aging can be classified into physiological aging process over time and aging process due to environmental factors (Claude et al., Free radical Boil & Med, 26, 174, 1999).

As the skin ages, various metabolic activities are lowered, and cell activity is lowered, resulting in thinner, dry and wrinkled skin. The interest in anti-aging has been of major interest not only to researchers but also to many ordinary people, and research on this is expected to become more active over time.

The structure of the skin is divided into four categories: the stratum corneum, the epidermis, the dermis and the subcutaneous tissue. At the top of the stratum corneum, dead cells are layered, and soft fibrous proteins called keratin fill the cells and protect the skin. Most of the epidermal cells are filled with keratinocytes that make up keratinocytes. The dermis is a connective tissue composed of glue fibers and elastic fibers, which is tough and elastic. In addition, the skin tissue is a connective tissue layer under the dermis, and serves to connect the skin and fascia.

External factors affecting skin aging include humidity, tobacco smoke, pollution, wind, temperature and ultraviolet rays. In particular, aging due to ultraviolet rays is called photoaging. The shape seen in chronic sun-damaged skin is an abnormal deposition of elastic fibrous material in the upper collagen of the dermis, an increase in proteoglancan, and a significant decrease in collagen, the main protein of the dermis (Li et al., Cancer Research, 56, 284, 1996).

Collagen gives strength and tension to the skin, which protects the skin from external irritation or force. Since collagen accounts for 90% of the dermal layer, collagen reduction is closely related to aging of the skin.

Matrix Metalloproteinases (MMPs) depend on zinc ions and are proteolytic enzymes that degrade the extracellular matrix (ECM) present in the basement membrane and interstitial tissues (Steven D shapiro, Cell Biol, 10, 602, 1998). It is synthesized into inactive spheres and then activated by proteolytic hydrolysis. The activity of MMPs is known to be regulated by gene expression, activation of inactive enzymes, and inhibition of enzyme activity (Woodhouse et al., Cancer , 80, 1529, 1997; Wass et al., Br J Cancer, 86, 1876, 2002; Nagase et al., J Biol Chem, 274, 21491, 1999).

About 20 matrix metalloproteinases (MMPs) are known depending on substrate specificity. Unlike MMP-2, which is always expressed and functioning, MMP-9 is characterized by increased expression by stimulation of inflammatory mediators such as TNF-α and is regulated by specific transcription factors such as NFκB (Sanseau et al., J Biol Chem, 227, 35766, 2002). It can decompose most of the extracellular matrix, thus maintaining normal physiological functions during tissue reconstruction such as the development of wound healing fetus, neovascularization, menstruation, ovulation, and pregnancy, but if excessively expressed, skin aging, Involvement in several pathologies has been reported, including rheumatoid arthritis, chronic ulcers, periodontitis, arteriosclerosis, late-night growth and tumor cell infiltration and metastasis (Linda et al., Chem Biol, 2, 466, 1998).

Repeated UV exposure is known to reduce collagen synthesis and increase the expression of MMP-9, an enzyme that degrades collagen and other matrix proteins, through multiple signaling pathways (Lee et al., J.). Dermatol Sci, 17, 182, 1998). In fact, even one UV irradiation increases the activity of MMP-9 in the skin and significantly breaks down collagen in the skin, which has been reported to play an important role in photoaging and MMP-9 affects collagen breakdown of the dermis. Lee et al., J. Dermatol Sci, 17, 182, 1998.

When collagen is reduced by MMP-9, the skin's strength and tension decreases, and the function of protecting the skin is significantly reduced, thereby accelerating skin aging. As such, the increased activity of MMP-9 breaks down the skin constituents and accelerates skin aging, thereby developing a new leader that improves or prevents skin aging by using a compound that inhibits the expression of MMP-9 genes. It is expected to be used as an indicator.

Accordingly, the present inventors have diligently tried to find a compound that can suppress skin aging, and as a result, a bis3,5-dimethoxychalcone compound inhibits the gene expression of MMP-9, thereby constituting the skin component. The present invention was confirmed to inhibit the degradation of phosphorus collagen.

In conclusion, the present invention provides a bis 3,5-dimethoxychalcone compound having an inhibitory activity of Matrix Metalloproteinase-9 (MMP-9), which promotes collagen degradation, and the compound as a skin aging inhibitor. Its main purpose is to provide new uses for use.

In order to achieve the above object, the present invention inhibits the expression of Matrix Metalloproteinase-9 (MMP-9) gene to inhibit the degradation of collagen, a component of skin, bis 3,5-dimethoxy Provided is a chalcone (bis3,5-dimethoxychalcone) compound and a skin aging inhibitor composition comprising the compound.

In the present invention, the skin aging inhibitor composition includes a pharmaceutical composition, cosmetic composition, and health functional food that can prevent skin aging and / or improve skin wrinkles.

According to the present invention as described above, the bis3,5-dimethoxychalcone compound inhibits the expression of Matrix Metalloproteinase-9 (MMP-9) gene and degrades collagen. Since it has an effect of inhibiting the skin aging can be usefully used as an active ingredient of the composition for preventing skin aging and / or improve the wrinkles caused by skin aging.

1 is a hydrogen nuclear magnetic resonance spectroscopy spectrum of bis 3,5-dimethoxychalcone (using a 400 MHz Bruker nuclear magnetic resonance spectrometer).
2 is a carbon nuclear magnetic resonance spectroscopy spectrum of bis 3,5-dimethoxychalcone (using a 400 MHz Bruker nuclear magnetic resonance spectrometer).
Figure 3 shows the effect of suppressing the expression of MMP-9 gene induced by TNF-α when the bis 3,5-dimethoxychalcone compound (DMC) of the present invention is added to HCT116 cells, a human colorectal cancer cell line.

Hereinafter, the present invention will be described in detail.

The present invention provides a bis 3,5-dimethoxychalcone compound represented by the following formula (1).

[Formula 1]

In the present invention, the bis 3,5-dimethoxychalcone compound is a substrate metalloproteinase-9 induced by tumor necrosis factor-α (TNF-α). (Matrix Metalloproteinase-9; hereinafter MMP-9) by inhibiting the expression of the collagen which is a component of the skin by inhibiting the gene.

In addition, the present invention provides a method for preparing bis 3,5-dimethoxychalcone of the formula (1).

Compounds of the present invention can be prepared by synthetic methods well known in the art, in the present invention was synthesized based on the method of Scheme 1 below.

Scheme 1

Specifically, the present invention (1) 3,5-dimethoxyacetophenone (3,5-Dimethoxyacetophenone) as a starting material dissolved in an organic solvent with 3,5-dimethoxybenzaldehyde (3,5-dimethoxybenzaldehyde) Doing; (2) slowly adding an alkaline solution to the solution at 3 to 5 ° C. and stirring at room temperature for 24 hours to react; (3) cooling the reaction mixture to 3 to 5 ° C. to add an acidic solution to acidify the solution, and then removing the organic solvent under reduced pressure; (4) extracting the organic solvent-free solution into a chloroform solution, drying the organic layer, removing the filtrate with a desiccant, and then depressurizing the filtrate; And (5) separating and purifying the residue obtained by distillation under reduced pressure through column chromatography to obtain a final compound bis3,5-dimethoxychalcone. Can be. At this time, the organic solvent in the step (1) is preferably using ethanol, the alkaline solution of the step (2) and the acidic solution of the step (3) is 50% KOH solution (w / w) and It is recommended to use 3N HCl solution.

The present invention also provides a method of inhibiting the degradation of collagen through the inhibition of gene expression of MMP-9 induced by TNF-α.

In addition, the present invention provides a novel use of the bis 3,5-dimethoxychalcone compound of Formula 1 as a skin aging inhibitor.

Specifically, the present invention can prevent skin aging and / or treat skin wrinkles comprising the bis3,5-dimethoxychalcone compound or a pharmaceutically acceptable salt thereof as an active ingredient. It provides a pharmaceutical composition.

The compounds of the present invention can also be synthesized by the methods presented by the inventors or by conventional methods of synthesizing similar compounds.

In addition, the compounds of the present invention may be prepared with pharmaceutically acceptable salts and solvates according to methods conventional in the art.

As salts are acid addition salts formed with pharmaceutically acceptable free acids. Acid addition salts are prepared by conventional methods, for example, by dissolving a compound in an excess of aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. Equal molar amounts of the compound and acid or alcohol (eg, glycol monomethyl ether) in water can be heated and then the mixture is evaporated to dryness or the precipitated salts can be filtered off by suction.

In this case, organic acids and inorganic acids may be used as the free acid, and hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, and the like may be used as the inorganic acid, and methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, Citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, glycolic acid gluconic acid), galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, and the like.

Bases can also be used to make pharmaceutically acceptable metal salts. An alkali metal or alkaline earth metal salt is obtained by, for example, dissolving a compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and then evaporating and drying the filtrate. At this time, as the metal salt, it is particularly suitable to prepare sodium, potassium or calcium salt, and the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (for example, silver nitrate).

Pharmaceutically acceptable salts of Formula 1 include salts of acidic or basic groups which may be present in compounds of Formula 1 unless otherwise indicated. For example, pharmaceutically acceptable salts include sodium, calcium and potassium salts of the hydroxy group, and other pharmaceutically acceptable salts of the amino group include hydrobromide, sulfates, hydrosulfates, phosphates, hydrogen phosphates, dihydrogen Phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts. It can be prepared through.

The bis 3,5-dimethoxychalcone compound according to the present invention prepared as described above is excellent in inhibiting the expression of MMP-9 gene induced by TNF-α, and thus may be used as an anti-aging agent. Can be.

In addition, the present invention is a bis 3,5-dimethoxychalcone (bis3,5-dimethoxychalcone) compound of the formula (1) as an active ingredient, and the prevention of skin aging and / and skin wrinkles comprising a pharmaceutically acceptable carrier and Provided are pharmaceutical compositions for treatment.

Pharmaceutical compositions comprising bis3,5-dimethoxychalcone compounds of the present invention may further comprise a suitable carrier, excipient or diluent according to conventional methods.

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

Pharmaceutical compositions comprising a compound of the present invention are each formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, or the like, external preparations, suppositories, or sterile injectable solutions according to conventional methods. Can be used.

Specifically, when formulated, it may be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrating agents, surfactants, etc. which are commonly used. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose (sucrose), lactose (lactose), gelatin can be prepared by mixing. It can also be used as lubricants such as magnesium stearate, talc in addition to simple excipients. Liquid preparations for oral use include suspensions, solvents, emulsions, and syrups.In addition to the commonly used simple diluents, water and liquid parazin, various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. May be included. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate and the like can be used. As a base of suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

Preferred dosages of the compounds of the present invention will be appropriately selected by those skilled in the art depending 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. However, for the desired effect, the compounds of the present invention may be administered in divided doses of 10 to 500 mg once to several times daily. The compound of the present invention in the composition should be present in an amount of 0.01 to 50% by weight relative to the total weight of the total composition.

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

The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes, and all modes of administration can be expected, for example, oral, rectal or intravenous, muscle, subcutaneous, It can be administered by intrauterine dural or intracerebroventricular injection.

In addition, the present invention provides a cosmetic composition that can prevent skin aging or / and improve the skin wrinkles comprising the bis 3,5-dimethoxychalcone (bis3,5-dimethoxychalcone) compound of Formula 1 as an active ingredient do.

When the bis 3,5-dimethoxychalcone compound according to the present invention is used as a cosmetic, including conventional cosmetic base components in addition to the compound, for example, stabilizers, solubilizers, Conventional inclusion agents such as pigments and perfumes, and carriers may be included. In addition, the cosmetics may be prepared in any formulation conventionally prepared in the art, and are not particularly limited, for example, cosmetic lotions, essences, lotions, pastes, surfactant-containing cleansing, creams, packs, gels, ointments, It may have a formulation of powder, patch or spray (spray).

When the formulation of the cosmetic composition is a paste, cream or gel, the carrier component may be animal oil, vegetable oil, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc and zinc oxide. One or more selected from the group consisting of can be used, and when the formulation is a lotion, an essence, a solvent, a solubilizer or an emulsifier is used as the carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate At least one selected from the group consisting of benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils, glycerol aliphatic esters, polyethylene glycols and sorbitan fatty acid esters, and the like.

In addition, when the formulation of the cosmetic composition is a powder or spray, one or more selected from the group consisting of lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, etc. may be used as a carrier component, and in particular, spray May further comprise propellants such as chlorofluorohydrocarbons, propane / butane or dimethyl ether. In addition, in the case where the formulation of the cosmetic composition is a surfactant-containing cleansing agent, as a carrier component, an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, One or more selected from the group consisting of fatty acid amide ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, ethoxylated glycerol fatty acid esters, and the like can be used.

At this time, the compound in the cosmetic is preferably added at 0.01 to 50% by weight, preferably 0.01 to 30% by weight of the total weight.

In addition, the present invention is a health functional food composition that can prevent skin aging or / and improve the skin wrinkles comprising the bis 3,5-dimethoxychalcone (bis3,5-dimethoxychalcone) compound of the formula (1) as an active ingredient To provide.

Examples of the food to which the compound of the present invention can be added include various foods, beverages, gums, tea vitamin complexes, and health functional foods. It may also be added to food or beverages for the purpose of preventing cerebral disease symptoms.

At this time, the amount of the extract in the food or beverage is generally added to the health functional food composition of the present invention 0.01 to 50% by weight, preferably 0.01 to 30% by weight of the total food weight, the health beverage composition is 100ml It can be added in a ratio of 0.01 to 5g, preferably 0.1 to 3g on the basis of.

The health functional food of the present invention includes the form of tablets, capsules, pills, liquids, and the like, and the health beverage composition of the present invention contains the compound as an essential ingredient in the indicated ratio, and there is no particular limitation on the liquid component. Like beverages may further contain various flavors or natural carbohydrates.

Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose, such as maltose, sucrose and the like, and conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and the like. Sugar alcohols such as xylitol, sorbitol, and erythritol. In addition to the above, natural flavors, taumartins, stevia extracts such as rebaudioside A, glycyrrhizin and the like and synthetic flavors, saccharin, aspartame and the like can be advantageously used as flavoring agents.

In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic and natural flavors, colorants and enhancers (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and salts thereof. , Organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. These components may be used independently or in combination, and the proportion of such additives is not so critical but is usually selected in the range of 0 to about 20 parts by weight relative to 100 parts by weight of the composition of the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these examples are for illustrative purposes only and that the scope of the present invention is not construed as being limited by these examples.

Example 1 Synthesis of Bis3,5-Dimethoxychalcone

In the present invention, the following method was used to synthesize bis3,5-dimethoxychalcone.

Dissolve 3,5-dimethoxyacetophenone (3,5-Dimethoxyacetophenone, 900mg, 5mmol) and 3,5-dimethoxybenzaldehyde (3,5-dimethoxybenzaldehyde, 830mg, 5mmol) in 20ml ethanol, and then at 4 ℃ 8 ml of 50% aqueous KOH solution was slowly added for about 10 minutes. After stirring the mixed solution at room temperature for 24 hours, the temperature was lowered to about 4 ℃. 30 ml of 3N HCl solution is added to the cooled solution to make an acidic solution, and ethanol used as a solvent is distilled under reduced pressure. The aqueous solution was extracted three times with 40 ml of chloroform solution and the combined organic layers were dried using magnesium sulfate. The desiccant was filtered under reduced pressure and the filtrate was distilled under reduced pressure. The residue obtained by distillation under reduced pressure was separated and purified through column chromatography with a developing solvent (EtOAc: Hexane-1: 4) to obtain 1.28 g (78%) of the title compound. Nuclear magnetic resonance spectroscopy was performed to confirm the final product. The device used was a Bruker 400 MHz device. Hydrogen nuclear magnetic resonance spectra and carbon nuclear magnetic resonance spectra are shown in FIGS. 1 and 2, respectively, and chemical mobility is as follows.

1H-NMR (400Mhz) δ: 3.81 (s), 3.84 (s), 6.51 (m), 6.65 (m), 6.75 (d, J = 2.1HZ), 7.12 (d, J = 2.1Hz), 7.40 ( d, J = 15.6), 7.69 (d, J = 15.6 Hz)

13C-NMR (100Mhz) δ: 55.5 (q), 55.7 (q), 102.9 (d), 105.1 (d), 106.5 (d), 122.6 (d), 136.8 (s), 140.2 (s), 145.0 ( d), 161.0 (s), 161.2 (s), 190.1 (s)

Melting | fusing point of this compound was 110-111 degreeC.

Example 2. Confirmation of the inhibitory effect of MMP-9 gene expression of bis3,5-dimethoxychalcone

Luciferase reporter assay to measure MMP-9 gene promoter activity in order to confirm the inhibitory effect of TNF-α-induced MMP-9 gene expression of bis3,5-dimethoxychalcone compounds (TNF-α) luciferase reporter essay) was used. The MMP-9 gene promoter reporter was prepared by integrating the transcription control site (base sequence -925- +13 base pair) of the human MMP-9 gene by PCR and inserting it into a pGL4-basic vector (Promega, Medison, Wisconsic, USA). pGL4 / MMP-9-Luc (-925 / + 13) vector was used (Shin SY et al. Mol Cancer Res 8, 507-519, 2010).

Using the analyzed results, 0.5 μg of the pGL4 / MMP-9-Luc (-925 / + 13) reporter plasmid was transferred to HCT116 cells, a human colorectal cancer cell line purchased from the American Type Culture Collection, USA (ATTC). fuGENE6) was used for intracellular injection. 48 hours after DNA injection, 10 ng / ml TNF-α alone or 10 ng / ml TNF-α and 20 μg / ml bis 3,5-dimethoxychalcone were treated.

After drug treatment, cells cultured for another 12 hours were harvested and lysed, and luciferin fluorescence was measured by adding 50 µl of luciferin as a substrate to the cell lysate. Cell lysates and substrates Luciferin was used in the Dual-Glo Luciferase Assay Kit purchased from Promega (Madision, WI, USA).

As shown in FIG. 3, TNF-α increased luciferase enzyme activity by 2.8-fold, indicating increased expression of MMP-9 gene by TNF-α. However, in the experimental group treated with TNF-α and bis 3,5-dimethoxychalcon of the present invention, the activity of luciferase by TNF-α was completely inhibited.

Accordingly, it was confirmed that bis3,5-dimethoxychalcone of the present invention inhibits MMP-9 gene expression activated by TNF-α at the transcription level.

As described above, specific portions of the contents of the present invention have been described in detail, and for those skilled in the art, these specific techniques are merely preferred embodiments, and the scope of the present invention is not limited thereto. Will be obvious. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (13)

Bis 3,5-dimethoxychalcone compound represented by the following formula (1).
[Formula 1]

The method of claim 1,
The compound inhibits gene expression of Matrix Metalloproteinase-9 (MMP-9) induced by Tumor necrosis factor-α (TNF-α). A bis 3,5-dimethoxychalcone compound characterized by inhibiting the decomposition of phosphorus collagen.
The method of claim 1,
Bis 3,5-dimethoxychalcone compound, characterized in that the compound is used as a skin aging inhibitor.
(1) dissolving in 3,5-dimethoxyacetophenone (3,5-dimethoxybenzaldehyde) in an organic solvent with 3,5-dimethoxybenzaldehyde as a starting material;
(2) slowly adding an alkaline solution to the solution at 3 to 5 ° C. and stirring at room temperature for 24 hours to react;
(3) cooling the reaction mixture to 3 to 5 ° C. to add an acidic solution to acidify the solution, and then removing the organic solvent under reduced pressure;
(4) extracting the organic solvent-free solution into a chloroform solution, drying the organic layer, removing the filtrate with a desiccant, and then depressurizing the filtrate; And
(5) separating and purifying the residue obtained by distillation under reduced pressure through column chromatography to obtain a final compound bis3,5-dimethoxychalcone. A method for producing bis 3,5-dimethoxychalcone according to claim 1.
The method of claim 4, wherein
In the process (1), the organic solvent is a method for producing bis 3,5-dimethoxychalcon (bis3,5-dimethoxychalcone), characterized in that ethanol.
Claim 1, bis 3,5-dimethoxychalcone (bis3,5-dimethoxychalcone) compound or a pharmaceutically acceptable salt thereof as a active ingredient comprising a pharmaceutical composition for preventing and treating skin aging.
A pharmaceutical composition for preventing and treating skin wrinkles comprising the bis3,5-dimethoxychalcone compound of claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
The method according to claim 6 or 7,
The composition is a pharmaceutical composition for the prevention and treatment of skin aging or wrinkles, characterized in that it further comprises a pharmaceutically acceptable carrier.
Claim 1, bis 3,5-dimethoxychalcone (bis3,5-dimethoxychalcone) compound comprising a compound for preventing and improving skin aging comprising as an active ingredient.
A cosmetic composition for preventing and improving skin wrinkles comprising the bis 3,5-dimethoxychalcone compound of claim 1 as an active ingredient.
11. The method according to claim 9 or 10,
The cosmetic composition is a cosmetic composition, characterized in that the lotion, essence, lotion, cream, pack, gel, ointment, powder, patch or spray.
Claim 1, bis 3,5-dimethoxychalcone (bis3,5-dimethoxychalcone) compound comprising an active ingredient for preventing skin aging and improving health functional food composition.
Claim 1, bis3,5-dimethoxychalcone (bis3,5-dimethoxychalcone) compound containing the active ingredient for preventing skin wrinkles and improving health food composition.

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