KR20110047774A - Isoflavone Derivatives and Composition Comprising the Same - Google Patents

Abstract

PURPOSE: A composition containing isoflavone derivatives is provided to ensure high stability, solubility, anti-aging, and anti-inflammation. CONSTITUTION: An isoflavone derivative has a structure of chemical formula I. A cosmetic composition contains the isoflavone derivative. The cosmetic composition additionally contains vitamin, surfactant, emulsifying agent, pigment, perfume, stabilizing agent, antiseptic, antioxidant, UV protector, pH adjusting agent, or chelate. A food composition contains the isoflavone derivative. The food composition additionally contains organic acid, phosphoric acid, antioxidant, lactose casein, dextrin, glucose, sugar, or sorbitol. A pharmaceutical composition contains the isoflavone derivative. The pharmaceutical composition additionally contains a carrier, excipient, disintegrant, sweetener, coating agent, lubricant, flavoring agent, antioxidant, buffer, diluent, dispersing agent, or binder.

Description

Isoflavone Derivatives and Composition Comprising the Same}

Embodiments of the present invention relate to isoflavone derivatives and cosmetic, food and pharmaceutical compositions comprising the same.

Soybean is a protein-containing food, widely known as a raw material of functional food, and its usefulness is being actively researched. Looking at the useful components of soybeans, it contains minerals as well as proteins, carbohydrates and fats, which are the main nutrients, and isoflavones, lecithin, peptides, amino acids, etc.

Of these, isoflavones are called phytoestrogens because they have properties similar to the female hormone estrogen. Isoflavones exist in the form of glycosides linked to beta-glycosides or in the form of nonglycosides in which sugars have been separated. Nonglycosides include genistein, daidzein, and glycidin, and glycosides include genistin, daidzin, and glycidin. . Soybean-derived non-fermented foods contain a large amount of glycosides, while fermented foods contain mainly non-glycosides as sugars are degraded from glycosides by bacteria related to fermentation.

Isoflavones are known to have a protective effect against ultraviolet rays, a collagen degrading enzyme inhibitory effect, an anti-aging effect, an antioxidant effect, and an anti-inflammatory effect.

However, in order to increase the utilization of isoflavones, development of active isoflavones with high solubility and stability is required.

Embodiments of the present invention are to provide a novel isoflavone derivatives having high solubility and stability and excellent anti-aging and anti-inflammatory effects, and cosmetics, food and pharmaceutical compositions comprising the same.

In order to solve the above problems, embodiments of the present invention provides an isoflavone derivative having the structural formula (I).

Embodiments of the present invention also provide a cosmetic, food and pharmaceutical composition comprising the isoflavone derivatives.

Isoflavone derivatives according to the embodiments of the present invention are not only highly soluble and stable, but also have excellent anti-aging and anti-inflammatory effects, and thus may be usefully used in the manufacture of cosmetics, foods, and medicines.

Isoflavone, one of soy protein contained in soybean, is known to have protection from ultraviolet rays, collagen degrading enzyme inhibitory effect, anti-aging effect, antioxidant effect and anti-inflammatory effect. Soybean-derived isoflavones exist mainly in the form of glycosides in which sugars are bound. However, since glycosides are almost impossible to absorb in the body, they should be used in the form of active nonglycosides.

However, even in the case of isoflavones in the form of active nonglycosides, there is a problem in that they are insoluble in water due to their low solubility and they are easily reacted with oxygen, resulting in inferior stability. The need for development is increasing.

The present inventors have synthesized a novel active isoflavone derivative, and confirmed that the novel isoflavone derivative has an excellent anti-apoptotic and anti-inflammatory effect even at a low concentration compared to the known soybean-derived isoflavone nonglycoside. The present invention has been completed. In addition, the novel isoflavone derivatives are well dissolved in hydrophobic solvents by introducing fatty acid groups, thereby improving solubility and stability.

Embodiments of the present invention provide an isoflavone derivative having the structure of formula (I)

[Formula I]

Wherein R ₁ is hydrogen or hydroxy, R ₂ is hydrogen or alkoxy of C _16, n and m may be from 1 to 16 independently of each other.

In one embodiment of the present invention, in the isoflavone derivative having the structure of Formula I, R ₁ is hydrogen or methoxy, R ₂ is hydrogen or methoxy, and n and m may each independently be 1 to 16. .

In another embodiment of the invention, in the isoflavone derivative having the structure of formula I, R ₁ is hydrogen, R ₂ is hydrogen or methoxy, n and m are each independently 1, 2, 3, 7 or 14 Can be.

In another embodiment of the present invention, in the isoflavone derivative having the structure of Formula I, R ₁ is hydrogen, R ₂ is hydrogen, n and m may be 1, 3, 5 or 14.

In another embodiment of the present invention, in the isoflavone derivative having the structure of formula I, R ₁ is hydrogen, R ₂ is methoxy, n and m may be 1, 3, 5 or 14.

In another embodiment of the present invention, in the isoflavone derivative having the structure of formula I, R ₁ is hydroxy, R ₂ is methoxy, n and m may be 1, 3, 5 or 14.

In another embodiment of the present invention, in the isoflavone derivative having the structure of Formula I, R ₁ is hydrogen, R ₂ is methoxy, and n and m may be 14.

Embodiments of the present invention also provide a cosmetic composition comprising an isoflavone derivative. As can be seen through the following examples, the isoflavone derivatives according to an embodiment of the present invention is not only excellent in preventing apoptosis by UV irradiation but also by inflammatory cytokines TNF-α and IL-6 by UV irradiation. The anti-inflammatory effect of inhibiting secretion is also excellent. In particular, it was confirmed that it has a better effect even at a lower concentration than the known isoflavone non-glycoside.

Ultraviolet light induces the expression of various inflammatory cytokines such as tumor necrotic factor (TNF) -α, interleukin-1α, IL-6, IL-8, IL-10. In particular, TNF-α plays an important role in the pathogenesis of inflammation and photoprotection in the skin inflammatory response induced by UV light. Therefore, analyzing the expression of TNF-α and IL-6 may be referred to as a primary analysis method in evaluating aging efficacy, and the cosmetic composition including isoflavone derivatives according to embodiments of the present invention is soluble and stable. Not only is this improved, it is also excellent in protecting against cell damage by ultraviolet rays and inhibiting expression of TNF-α and IL-6, which can be particularly useful in the manufacture of functional cosmetics for preventing skin aging.

In one embodiment of the present invention, a cosmetic composition comprising an isoflavone derivative, in addition to the above components, additives commonly used in cosmetics, such as vitamins, surfactants, emulsifiers, flavorings, pigments, stabilizers, preservatives, antioxidants, It may further comprise one or more additives selected from the group consisting of sunscreens, pH adjusters and chelating agents.

According to one embodiment of the present invention cosmetics using a cosmetic composition comprising an isoflavone derivative is not limited thereto in the formulation, for example, supple cosmetics, nourishing cosmetics, massage cream, nutrition cream, pack, gel, essence , Lipstick, makeup base, foundation, lotion, ointment, gel, cream, cleansing, face wash, soap, shampoo, rinse, treatment and essence. Such cosmetics may include conventional ingredients such as aqueous vitamins, oily vitamins, polymer peptides, polymer polysaccharides, sphingolipids, and the like, and may be readily prepared according to techniques well known to those skilled in the art.

According to one embodiment of the present invention, the content of the isoflavone derivative is not limited thereto, but may be 0.001 to 5 wt%, 0.01 to 5 wt%, or 0.01 to 1 wt% based on the total weight of the cosmetic composition.

Embodiments of the present invention also provide a food composition comprising an isoflavone derivative. The food composition has an antioxidant effect, collagen degrading enzyme inhibitory effect can be particularly useful in the manufacture of health functional foods and general foods that can exhibit a skin aging prevention effect. In addition, it has anti-inflammatory effects such as sepsis, arteriosclerosis, bacteremia, systemic inflammatory response syndrome, multi-organ dysfunction, cancer, osteoporosis, periodontitis, systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, spondyloarthritis, systemic Sclerosis, idiopathic inflammatory muscle disorders, Sjoegren's syndrome, systemic vasculitis, sarcoidosis, autoimmune hemolytic anemia, autoimmune thrombocytopenia, thyroiditis, diabetes mellitus, immune mediated kidney disease, central nervous system or peripheral nervous system Demyelinating diseases, idiopathic demyelinating polyneuritis, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuritis, hepatobiliary disease, infectious or autoimmune chronic active hepatitis, primary biliary cirrhosis, granulomatous hepatitis, Sclerotic cholangitis, inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, Irritable Bowel Syndrome, gluten-sensitive bowel disease, Whipple's disease, autoimmune or immune mediated skin disease, bullous skin disease polymorphic erythema, contact dermatitis, Prevention of inflammatory diseases such as psoriasis, allergic diseases, asthma, allergic rhinitis, atopic dermatitis, food intolerance, urticaria, lung immune diseases, eosinophilic pneumonia, idiopathic pulmonary fibrosis, irritable pneumonia, transplant rejection or graft versus host disease And it can be usefully used in the manufacture of dietary supplements and general foods that can exhibit a therapeutic effect.

In one embodiment of the invention, the food composition may further comprise one or more additives selected from the group consisting of organic acids, phosphates, antioxidants, lactose casein, dextrin, glucose, sugar and sorbitol. The organic acid may be, but is not limited to, citric acid, fumaric acid, adipic acid, lactic acid or malic acid, and the phosphate may be, but is not limited to, sodium phosphate, potassium phosphate, acid pyrophosphate or polyphosphate (polymeric phosphate), antioxidant The agent may be a natural antioxidant such as, but not limited to, polyphenols, catechins, alpha-tocopherols, rosemary extracts, licorice extracts, chitosan, tannic acid or phytic acid.

In another embodiment of the present invention, the food composition comprising isoflavone derivatives, in addition to isoflavone derivatives, flavors, colorants and neutralizing agents such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors ( Cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. . In addition, the food composition according to one embodiment of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. The proportion of such additives is generally not limited to, but is selected from the range of 0 to about 20 parts by weight, 5 to 20 parts by weight, or 5 to 15 parts by weight per 100 parts by weight of the composition of the present invention.

According to one embodiment of the invention, the formulation of the food composition may be in the form of a solid, powder, granules, tablets, capsules, liquids or beverages, but is not limited thereto.

In addition, the food composition comprising isoflavone derivatives is not limited to confectionery, sugar, ice cream products, dairy products, meat products, fish products, tofu or jelly, edible fats and fats, noodles, teas, beverages, special nutrition products, health supplements , Seasoned food, ice, ginseng products, kimchi pickles, raisins, fruits, vegetables, dried products of fruits or vegetables, cut products, fruit juices, vegetable juices, mixed juices, chips, noodles, livestock processed foods, fisheries Processed foods, dairy foods, fermented milk foods, legumes food, cereals, microbial fermented foods, bakery, condiments, meat processing, acidic beverages, licorice, herbs and the like can be used in the manufacture of food.

According to one embodiment of the invention, when using the food composition comprising the isoflavone derivatives in the manufacture of health functional food can be used as 0.01 to 15% by weight, or 0.1 to 10% by weight of the total food weight, beverage When used in the preparation of the present invention may be used in 0.02 to 10% by weight, or 0.3 to 1% by weight of the total beverage weight.

Embodiments of the present invention also provide a pharmaceutical composition comprising an isoflavone derivative. As can be seen through the following examples, the isoflavone derivatives according to the embodiments of the present invention not only have an excellent cytoprotective effect of preventing apoptosis by ultraviolet irradiation and increasing the activity of damaged cells, but also inflammatory cytokines It has an anti-inflammatory effect by inhibiting the expression of TNF-α and IL-6. In particular, it was confirmed that it has a better effect even at a lower concentration than conventionally known isoflavone non-glycoside.

Pharmaceutical compositions comprising isoflavone derivatives according to embodiments of the present invention may be prepared in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories or sterile injectables according to conventional methods. It can be used in the form of a suitable carrier, excipients, disintegrants, sweeteners, coatings, swelling agents, lubricants, lubricants, flavoring agents, antioxidants, buffers, bacteriostatics, diluents commonly used in the manufacture of pharmaceutical compositions It may further comprise one or more additives selected from the group consisting of, dispersants, surfactants, binders and lubricants.

Specifically, carriers, excipients and diluents are lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil can be used, and when formulated, commonly used fillers, extenders, binders, wetting agents, bores It can be prepared using diluents or excipients such as release, surfactant, and the like. 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 or lactose, gelatin in the composition. You can mix and mix etc. In addition to simple excipients, lubricants such as magnesium styrate and talc may also be used. Oral liquid preparations include suspensions, solvents, emulsions, syrups, and the like, and may include various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, and the like. 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. Witsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like may be used as the base material of the suppository.

Pharmaceutical compositions comprising isoflavone derivatives according to embodiments of the invention can be used for the prevention and treatment of inflammatory diseases. Accordingly, embodiments of the present invention provide a pharmaceutical composition for the prevention and treatment of inflammatory diseases comprising isoflavone derivatives, the use for the prevention and treatment of inflammatory diseases of isoflavone derivatives, and administering to the subject a therapeutically effective amount of isoflavone derivatives. It provides a method for preventing and treating inflammatory diseases comprising.

Specifically, the inflammatory disease is sepsis, arteriosclerosis, bacteremia, systemic inflammatory response syndrome, multi-organ dysfunction, cancer, osteoporosis, periodontitis, systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, spondyloarthrosis, systemic sclerosis , Idiopathic inflammatory muscle disorders, Sjoegren's syndrome, systemic vasculitis, sarcoidosis, autoimmune hemolytic anemia, autoimmune thrombocytopenia, thyroiditis, diabetes mellitus, immune mediated kidney disease, central nervous system or peripheral nervous system dehydration Early disease, idiopathic demyelinating polyneuritis, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuritis, hepatobiliary disease, infectious or autoimmune chronic active hepatitis, primary biliary cirrhosis, granulomatous hepatitis, sclerosis Cholangitis, Inflammatory bowel disease (IBD), Ulcerative colitis, Crohn's disease, Irritable Bowel Syndrome, gluten-sensitive bowel disease, Whipple's disease, autoimmune or immune mediated skin disease, bullous skin disease polymorphic erythema, contact dermatitis, Psoriasis, allergic diseases, asthma, allergic rhinitis, atopic dermatitis, food intolerance, urticaria, pulmonary immune diseases, eosinophilic pneumonia, idiopathic pulmonary fibrosis, irritable pneumonia, transplant rejection or graft versus host disease .

According to one embodiment of the present invention, the isoflavone derivative may be administered to a subject by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

Preferred dosages of the isoflavone derivatives may vary depending on the condition and weight of the patient, type and extent of disease, drug form, route of administration and duration and may be appropriately selected by those skilled in the art. According to one embodiment of the present invention, but not limited thereto, the daily dosage may be 0.01 to 10,000 mg / kg, specifically 0.1 to 10,000 mg / kg, more specifically 0.1 to 1,000 mg / kg. Administration may be administered once a day or divided into several times, thereby not limiting the scope of the invention.

In embodiments of the present invention, the 'object' includes, but is not limited to, humans, orangutans, chimpanzees, mice, rats, dogs, cattle, chickens, pigs, goats, sheep, and the like.

Hereinafter, examples will be described in detail to help understand the present invention. However, the following examples are merely to illustrate the content of the present invention is not limited to the scope of the present invention. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.

< Example  1> High Purity Isoflavones Nonglycoside  Produce

Soy isoflavone crude extract (= 20%, soybean extract powder S20, Seolim Bio Co., Ltd.) using beta-glucosidase (β-glucosidase) per g of 2g at 37 ℃, pH 4.0 conditions for 2 hours The isoflavone glycosides were converted to nonglycosides by reaction with stirring. The reaction product was centrifuged (7000rpm, 20 minutes), the supernatant was removed, and the precipitate was recovered. Then, the precipitate was recovered by washing three times by adding 10 parts by weight of water with an extraction solvent. The precipitate was washed three times in the same manner using 10 parts by weight of 50% methanol, and the precipitate was lyophilized to obtain a powder.

Purity and recovery of the isoflavone non-glycoside to the powder were sampled on a TLC plate, developed in a developing solvent (chloroform: methanol: water = 65: 25: 4), dried and qualitatively analyzed at 254 nm and 366 nm.

In addition, the isoflavone nonglycoside previously separated and purified by a series of methods was quantitatively analyzed through HPLC analysis. The sample was injected into the column at 500 ppm concentration in dimethyl sulfoxide, 1.0 μl was injected into the column and the solvent was flowed at a flow rate of 1.0 mL / min. The solvent consisted of two mobile phases, water / acetic acid (100/3, v / v, solvent A) and acetonitrile / acetic acid (100/3, v / v, solvent B). Used: 15-35% solvent A (30 minutes). The detection wavelength was set to 254 nm.

FIG. 1 shows the results of measuring isoflavone non-glycoside standards (lane 3) and soy isoflavone crude extracts (lane 1) and enzymes by converting the isoflavone glycosides into non-glycosides. The comparative TLC photograph is shown. 1 qualitatively confirming that the final reaction product was concentrated to high purity as it passed through the separation and purification step.

2 shows the results of quantitative analysis using HPLC. Peak 1 represents didze, Peak 2 represents glycine, and Peak 3 represents genistein. The contents of Dyzedein, Glycsteine, and Genistein were 25.8%, 61.8%, and 6.8%, respectively. The content of total isoflavone nonglycoside was 94.4%, and the high purity isoflavone nonglycoside was confirmed to be more than 90% purity.

< Example  2> isoflavones Nonglycoside Alkyl  Derivative manufacturing

In order to synthesize a compound in which two palmitoyl groups were introduced, the isoflavone nonglycoside (1.00 g, 3.70 mmol) obtained in Example 1 was dissolved in anhydrous dimethylformamide (40 mL), and potassium tertiary butoxide at room temperature. Side (Potassium tert-butoxide, 1.40 g, 12.5 mmol) was added. After stirring at room temperature for 2.5 hours, a solution of palmitoyl chloride (3.30 g, 12.0 mmol) was added dropwise to dimethylformamide (10 mL) and stirred at room temperature for 12 hours. Water was added to the reaction mixture, extracted with ethyl acetate and dried over anhydrous sodium sulfate. The reaction mixture was purified by column chromatography (ethyl acetate: hexane = 1: 1).

Also in the same manner as above, isoflavone derivatives in which acetyl, butyryl and hexanoyl groups were introduced using acetyl chloride, butyryl chloride and hexanoyl chloride instead of palmitoyl chloride were prepared.

For HPLC analysis, the sample was injected with 1.0 μl into the column at 500 ppm concentration in dimethyl sulfoxide and the solvent was flowed at a flow rate of 1.0 mL / min. The solvent consisted of two mobile phases, water / acetic acid (100/3, v / v, solvent A) and acetonitrile / acetic acid (100/3, v / v, solvent B). Used: 15-100% Solvent A (60 minutes). The detection wavelength was set to 254 nm.

3 shows the structure of an isoflavone derivative in which two palmitoyl groups are introduced through the above method, and Peak 1 of FIG. 4 shows the result of HPLC analysis of the compound.

On the other hand, in order to synthesize a compound in which one palmitoyl group was introduced, 1.1 equivalents of potassium tertiary butoxide and 1.2 equivalents of palmitoyl chloride were used in the isoflavone nonglycoside (0.10 g).

5 shows the structure of an isoflavone derivative in which one palmitoyl group is introduced, and Peak 1 of FIG. 6 shows the result of HPLC analysis of the compound.

< Example  3> Anti-apoptosis Effect by UV Light

MTT analysis method was used to investigate the effect of apoptosis by ultraviolet light and anti-apoptosis of the samples according to Examples 1 and 2. The cell line used in the experiment was a human skin keratinocyte cell line. Human skin keratinocytes were inoculated into 12 well plates at 1 × 10 ⁵ per well and treated at 37 ° C. using Dulbecco's modified eagle (DMEM) medium containing 10% FBS and 1% Anti-biotic / Anti-mycotic solution (AA). Incubated for 24 hours in a 5% CO ₂ incubator and irradiated with ultraviolet rays of 312nm, 15mJ / ㎠. After UV irradiation, isoflavone non-glycosides and derivatives thereof were administered to DMEM medium containing fetal calf serum treated by concentration and further incubated for 24 hours. Dosage concentrations were 0.01%, 0.001%, and 0.0001% for isoflavone nonglycosides, and 0.0004%, 0.0002%, 0.0001%, and 0.00005% for alkyl derivatives thereof. After further cultivation after UV irradiation, the culture medium was removed and 1 ml of 0.33 g / L MTT solution was added to each well and incubated in 37 ° C. and 5% CO ₂ incubator for 90 minutes. After the incubation, the MTT solution was removed, shaken at room temperature for 20 minutes with 1 ml of isopropanol acidified with 0.04N hydrochloric acid, and then the supernatant was recovered. By apoptosis was measured. [-] Denotes no treatment of ultraviolet light, [+] denotes ultraviolet treatment, and As denotes a positive control group treated with ascorbic acid as an antioxidant after UV irradiation.

7 is a view showing the results of the anti-apoptotic effect of the isoflavone glycosides and non-glycosides corresponding to the comparison group for the isoflavone derivatives of the experimental group, isoflavone glycosides (IG), isoflavone nonglycosides (IA1) and isoflavones The anti-glycoside shows the effect of preventing apoptosis by the ultraviolet irradiation of the separated purification of the genistein (IA2). According to FIG. 7, about 20% of cells were killed by ultraviolet irradiation ([+]), but when the isoflavone nonglycosides (IA1 and IA2) were treated after ultraviolet irradiation, a positive control group treated with ascorbic acid ([As]). Likewise, cell viability increased by 5-10%.

Figure 8 shows the cell death prevention effect by ultraviolet irradiation in the experimental group isoflavone derivatives. In the control group (untreated group), about 20% of the cells were killed by UV rays. Cytotoxicity was observed when one palmitoyl group was treated with modified isoflavone derivatives (IMP). As a result of treatment with modified isoflavone derivatives (IDP) in the palmitoyl group of dogs, it was confirmed that the cell viability increased to the normal level even though the isoflavone derivative was treated at a much lower concentration than the isoflavone nonglycoside.

As a result, isoflavone nonglycosides and derivatives of two isoflavone nonglycosides modified with two palmitoyl groups showed excellent cell protection from cell damage caused by UV light and increased cell activity as well as preventing cell death. It has been shown to be effective. In particular, the isoflavone derivatives modified with two palmitoyl groups showed better cell death prevention at much lower concentrations than isoflavone nonglycosides.

< Example  4> Anti-inflammatory Effects of Isoflavone Derivatives

In order to determine the anti-inflammatory effects of the samples according to Example 1 and Example 2, TNF-α ELISA assay and IL-6 ELISA assay were used. Human skin keratinocytes were used as the cell lines used in the experiment. Human skin keratinocytes were inoculated into 12 well plates at 1 × 10 ⁵ cells / well using Dulbecco's modified eagle (DMEM) medium containing 10% FBS and 1% Anti-biotic / Anti-mycotic solution (37). C, incubated for 24 hours in a 5% CO ₂ incubator and irradiated with ultraviolet rays of 312nm, 15mJ / ㎠. After UV irradiation, isoflavone non-glycosides and derivatives thereof were administered to DMEM medium containing fetal calf serum treated by concentration and further incubated for 24 hours. Dosage concentrations were 0.01%, 0.001% and 0.0001% for isoflavone nonglycosides and 0.0004%, 0.0002%, 0.0001% and 0.00005% for isoflavone derivatives thereof. The culture supernatants of human skin keratinocytes treated with UV light and further cultures were recovered and secreted into the culture solution, and TNF-α and IL-6 were measured using an ELISA kit. [-] Is ultraviolet treatment, [+] is ultraviolet treatment, and D is a positive control group treated with dexamethasone, an antioxidant after UV irradiation.

9 shows that isoflavone nonglycosides (IA) not only reduce the concentration of inflammatory cytokines TNF-α secreted by ultraviolet light but also inhibit TNF-α secretion to normal levels after 0.01% treatment. It was. In the case of isoflavone derivatives (IDP) modified with two palmitoyl groups, the same TNF-α secretion inhibitory effect was observed at 0.0004%, which is lower than that of the isoflavone nonglycoside.

FIG. 10 shows that isoflavone nonglycosides (IA) and isoflavone derivatives (IDPs) modified with two palmitoyl groups, in a concentration-dependent manner, decrease the secretion of IL-6, an inflammatory cytokine increased by ultraviolet light. .

Figure 1 is a TLC photograph showing the product of the soy isoflavone crude extract and isoflavone non-glycosides compared to the isoflavone non-glycoside standard.

FIG. 2 is a diagram showing the results of HPLC analysis of isolated and purified isoflavone nonglycosides. Peak 1 represents didze, Peak 2 represents glycine, and Peak 3 represents genistein.

3 shows the structure of an isoflavone derivative in which two palmitoyl groups are introduced.

Figure 4 shows the results of HPLC analysis of isoflavone derivatives in which two palmitoyl groups are introduced.

5 shows the structure of an isoflavone derivative in which one palmitoyl group is introduced.

Figure 6 shows the results of HPLC analysis of isoflavone derivatives in which one palmitoyl group was introduced.

7 is a view showing the results of measuring the change in cell viability after treatment with isoflavone glycosides and non-glycosides after UV irradiation.

8 is a view showing the results of measuring the change in cell viability after treatment with isoflavone derivatives after UV irradiation.

9 is a view showing the results of measuring the change in the amount of secretion of TNF-α according to the treatment of isoflavone non-glycoside and isoflavone derivatives.

10 is a view showing the results of measuring the change in the secretion amount of IL-6 according to the treatment of isoflavone non-glycoside and isoflavone derivatives.

Claims (15)

Isoflavone derivatives having the structure of Formula I: [Formula I]

Where R ₁ is hydrogen or hydroxy, R ₂ is hydrogen or C _{1 - 6} alkoxy, and, n and m are each independently 1-16. The method of claim 1, R ₁ is hydrogen or hydroxy, R ₂ is hydrogen or methoxy, n and m are each independently 1 to 16 isoflavone derivatives. The method of claim 2, R ₁ is hydrogen or hydroxy, R ₂ is hydrogen or methoxy, n and m are each independently 1, 3, 5 or 14 isoflavone derivatives. The method of claim 3, R ₁ is hydrogen, R ₂ is hydrogen, n and m are 1, 3, 5 or 14 isoflavone derivatives. The method of claim 3, R ₁ is hydrogen, R ₂ is methoxy, n and m are 1, 3, 5 or 14 isoflavone derivatives. The method of claim 3, R ₁ is hydroxy, R ₂ is methoxy, n and m are 1, 3, 5 or 14 isoflavone derivatives. The method of claim 3, R ₁ is hydrogen, R ₂ is methoxy, isoflavone derivative wherein n and m are 14; A cosmetic composition comprising the isoflavone derivative according to any one of claims 1 to 7. The method of claim 8, Cosmetic composition further comprising at least one additive selected from the group consisting of vitamins, surfactants, emulsifiers, perfumes, pigments, stabilizers, preservatives, antioxidants, sunscreens, pH adjusters and chelating agents. A food composition comprising an isoflavone derivative according to any one of claims 1 to 7. The method of claim 10, A food composition further comprising at least one additive selected from the group consisting of organic acids, phosphates, antioxidants, lactose casein, dextrins, glucose, sugars and sorbitol. A pharmaceutical composition comprising the isoflavone derivative according to any one of claims 1 to 7. The method of claim 12, Add one or more additives selected from the group consisting of carriers, excipients, disintegrants, sweeteners, coatings, swelling agents, lubricants, lubricants, flavoring agents, antioxidants, buffers, bacteriostatic agents, diluents, dispersants, surfactants, binders and lubricants Pharmaceutical composition comprising as. The method of claim 12, The pharmaceutical composition is a pharmaceutical composition for the prevention and treatment of inflammatory diseases. The method of claim 14, The inflammatory diseases include sepsis, arteriosclerosis, bacteremia, systemic inflammatory response syndrome, multi-organ dysfunction, cancer, osteoporosis, periodontitis, systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, spondyloarthropathy, systemic sclerosis, idiopathic Inflammatory muscle disorder, Sjoegren's syndrome, systemic vasculitis, sarcoidosis, autoimmune hemolytic anemia, autoimmune thrombocytopenia, thyroiditis, diabetes mellitus, immune mediated kidney disease, central nervous system or demyelinating disease of the peripheral nervous system , Idiopathic demyelinating polyneuritis, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuritis, hepatobiliary disease, infectious or autoimmune chronic active hepatitis, primary biliary cirrhosis, granulomatous hepatitis, sclerotic cholangitis, Inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease s disease, Irritable Bowel Syndrome, gluten-sensitive bowel disease, Whipple's disease, autoimmune or immune-mediated skin disease, bullous skin disease polymorphism, contact dermatitis, psoriasis, For prevention and treatment of inflammatory diseases such as allergic diseases, asthma, allergic rhinitis, atopic dermatitis, food intolerance, urticaria, lung immune diseases, eosinophilic pneumonia, idiopathic pulmonary fibrosis, irritable pneumonia, transplant rejection or graft versushost disease Pharmaceutical composition.

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