Composition and method of applying the same to the skin to inhibit cortisone reductase

Abstract

The present invention provides a composition for inhibiting cortisone reductase, which contains coumestrol extracted from beans as an active ingredient, and a cosmetic preparation containing the composition.

Description

Technical Field

[0001] This description , group product and a method of inhibiting cortisone reductase by applying this to the skin relates to.

Background Art

[0002] Stress has long been regarded as the root cause of all diseases. Especially in modern society, it is recognized as a very important social problem because it occurs excessively regardless of age, gender, due to various causes such as social factors like academics, work, marriage, child-rearing, and peripheral environmental factors like weather and traffic.

[0003] As society develops rapidly and diversifies, and the roles required of modern people increase, the number of people suffering from general anxiety disorders and mental illnesses due to various stresses is increasing. According to the "2006 Epidemiological Survey of Mental Disorders" released by the Ministry of Health and Welfare, the "one-year prevalence rate of mental disorders", which is the ratio of the population experiencing one or more mental disorders in 2006, was 17.1%. This means that one in six adults aged 18 to 64 had experienced one or more mental disorders, and the "lifetime prevalence rate of mental disorders", which is the ratio of the population experiencing one or more mental disorders throughout their lives as of 2006, was 30%, that is, one in three adults. Considering the recent increasing trend of mental disorders among teenagers due to excessive academic enthusiasm or various stresses, it can be said that the prevalence rate of the entire population is even higher.

[0004] Currently in clinical practice, anxiety disorders are treated by combining drug therapy and long-term psychotherapy. In the case of drug therapy, mainly benzodiazepine-based anti-anxiety drugs such as diazepam, lorazepam, clonazepam, and alprazolam are mainly used, and buspirone of the azapirone system is used as a drug that can selectively act on serotonin receptors and selectively relieve anxiety symptoms. Also, recently, research on stress regulators derived from natural products that can complement the side effects of such drugs has been actively conducted.

[0005] After the inventors continued their research on substances derived from natural products that can prevent or treat mental stress-related diseases, they confirmed that 11β-hydroxysteroid dehydrogenase type 1, which is a cortisol reductase in keratinocytes present in the epidermis under mental stress conditions, is activated to increase the cortisol concentration in the epidermis (increase the degree of reduction of cortisone to cortisol), and also confirmed that the phenomenon of reduced skin barrier function due to the activation of the 11β-hydroxysteroid dehydrogenase type 1 is completely different in its mechanism of action from the phenomenon caused by other causes not attributable to mental stress (such as physical injury and aging, etc.). Furthermore, they confirmed that coumestrol extracted from beans specifically inhibits the activity of the 11β-hydroxysteroid dehydrogenase type 1, and thus completed the present invention.

[0006] On the other hand, coumestrol is a substance mainly found in the seeds, roots, and leaves of plants of the Leguminosae and Compositae families. It is a type of isoflavonoid and is generally classified as a coumestan-based compound. Coumestrol is a component that is hardly present or not present at all in common beans and is produced only when the beans are germinated (Non-Patent Document 1), and it is known that its content increases as the initial germination days increase (Non-Patent Document 2). Also, although the exact mechanism of coumestrol is not known, it is known to promote the formation of connective tissues such as collagen in the skin and organ tissues, and it is presumed to have an anti-aging or anti-wrinkle effect from a histological aspect (Non-Patent Document 3).

[0007] In Patent Document 1, a pharmaceutical composition is described that uses an alfalfa extract containing coumestrol to reduce the blood lipid concentrations of cholesterol and triglycerides, which are the most important risk factors for cardiovascular diseases and myocardial infarction. Patent Document 2 describes the synthesis of coumestrol, followed by the esterification of ferulic acid and the synthesized coumestrol to synthesize 3,9-diferuloyl coumestrol, which has a strong antioxidant effect and promotes the activation of skin connective tissue, showing an anti-skin-aging effect and a skin-whitening effect, and describes a skin cosmetic containing the 3,9-diferuloyl coumestrol.

[0008] However, regarding whether coumestrol can prevent or treat the decline of skin barrier function by inhibiting the activation of cortisone reductase (11β-hydroxysteroid dehydrogenase 1) caused by mental stress, nothing is known at all.

Prior Art Documents

Patent Documents

[0009]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Non-Patent Documents

[0010]

Non-Patent Document 1

Non-Patent Document 2

[0011] One embodiment is to provide a (cosmetic) composition that can reduce the cortisol concentration induced by mental stress and shorten the barrier function recovery time of the stratum corneum by inhibiting the activity of 11β-hydroxysteroid dehydrogenase type 1, which is a factor causing a decrease in skin barrier function due to mental stress. Means for Solving the Problems

[0012] According to one embodiment, a composition for inhibiting cortisone reductase containing coumestrol extracted from beans as an active ingredient is provided.

[0013] The cortisone reductase may be 11β-hydroxysteroid dehydrogenase type 1.

[0014] The coumestrol may be contained in a concentration range of 0.001 μM to 1,000 μM.

[0015] The beans may include legumes selected from soybeans, peas, and mung beans, germinated beans germinated from the legumes, or combinations thereof.

[0016] The composition may be a cosmetic composition.

[0017] According to another embodiment, there is provided a method of inhibiting cortisone reductase by applying to the skin a composition containing, as an active ingredient, an effective amount of coumestrol extracted from beans. Effects of the Invention

[0018] According to one embodiment, by inhibiting the activity of 11β-hydroxysteroid dehydrogenase type 1, which is a factor causing a decrease in skin barrier function due to mental stress, the cortisol concentration induced by mental stress can be reduced, and the recovery time of the barrier function of the stratum corneum can be shortened. That is, among various causes of decreased skin barrier function, the phenomenon of decreased skin barrier function caused by mental stress can be specifically prevented and treated.

Brief Description of the Drawings

[0019] [Figure 1] The result of measuring the cortisol concentration in the cell culture medium using the ELISA method. [Figure 2] A western blotting photograph for confirming the protein expression of keratin1, which is a keratinocyte differentiation marker. [Figure 3] A western blotting photograph for confirming the protein expression of Filaggrin, which is a keratinocyte differentiation marker.

Modes for Carrying Out the Invention

[0020] Hereinafter, embodiments of the present invention will be described in detail so that those having ordinary knowledge in the technical field to which the present invention pertains can easily implement them. However, the present invention can be realized in various different forms and is not limited to the embodiments described herein.

[0021] In this specification, improving skin barrier function means inhibiting the activity of 11β-hydroxysteroid dehydrogenase type 1 present in the skin site damaged due to mental stress to reduce the cortisol concentration, and has nothing to do with suppressing oxidative stress due to physical trauma, aging, etc. or maintaining skin homeostasis. This is because suppressing oxidative stress due to physical trauma, aging, etc. or maintaining skin homeostasis is not caused by mental stress and their mechanisms are completely different.

[0022] In addition, the mental stress described in this specification has a different meaning from neurosis in the field of medicine. Neurosis generally refers to a distorted maladaptive state in which one cannot adapt well to psychological stress. However, the mental stress in this specification means a state in which, although one has adapted to psychological stress, the cortisone reductase (11β-hydroxysteroid dehydrogenase type 1) in epidermal keratinocytes is activated regardless of the will of the person concerned.

[0023] When a part such as a layer, a film, a region, or a plate is "on" another part in this specification, this includes not only the case where it is "directly above" the other part but also the case where there are other parts in between. Conversely, when a part is "directly above" another part, it means that there are no other parts in between.

[0024] Unless otherwise defined in this specification, "combination" means mixing or copolymerization. Also, "copolymerization" means block copolymerization or random copolymerization, and "copolymer" means block copolymer or random copolymer.

[0025] Hereinafter, a composition for inhibiting cortisone reductase according to one embodiment will be described.

[0026] The composition for inhibiting cortisone reductase according to one embodiment contains coumestrol extracted from beans as an active ingredient.

[0027] Since the coumestrol extracted from the beans has the effect of specifically inhibiting the activity of cortisone reductase present in epidermal keratinocytes under mental stress conditions, the composition according to one embodiment can prevent the skin barrier function from being reduced even under mental stress conditions or can quickly improve the skin barrier function weakened by mental stress.

[0028] Specifically, when subjected to mental stress, wound healing is delayed, the skin barrier function is reduced, the firmness of the stratum corneum decreases, or the recovery of the barrier function after injury is delayed. The mechanism can be broadly divided into two categories. One is that mental stress activates the hypothalamus-pituitary-adrenal system (HPA axis), increasing the secretion of glucocorticoids (GC) into the blood. The GC binds to GC receptors (GR) present in the epidermis and dermis, which are peripheral tissues, resulting in a decrease in skin barrier function. The other is that mental stress activates the cortisone reductase (11β-hydroxysteroid dehydrogenase 1) present in the keratinocytes of the epidermis, increasing the concentration of cortisol (the activated form of GC), thereby causing a decrease in skin barrier function. The composition according to one embodiment can prevent the decrease in skin barrier function by inhibiting the activation of cortisone reductase (11β-hydroxysteroid dehydrogenase 1) through the second mechanism.

[0029] The cortisone reductase may be 11β-hydroxysteroid dehydrogenase type 1. Coumestrol extracted from beans, which is included as an active ingredient in the composition according to one embodiment, can characteristically act on 11β-hydroxysteroid dehydrogenase type 1 to inhibit the activity of the cortisone reductase.

[0030] Accordingly, one embodiment provides a composition for inhibiting cortisone reductase, specifically a composition for inhibiting the activity of 11β-hydroxysteroid dehydrogenase type 1, containing coumestrol extracted from the beans as an active ingredient, which can contain the coumestrol in a pharmaceutically effective amount alone or in combination with one or more pharmaceutically acceptable carriers, excipients, or diluents.

[0031] The beans can include legumes selected from soybeans, peas, and mung beans, germinated beans germinated from the legumes, or combinations thereof. Specifically, as a composition for inhibiting cortisone reductase according to one embodiment, coumestrol or a natural product containing coumestrol and an extract thereof can be used as an active ingredient. The natural product containing coumestrol and an extract thereof can be obtained from legumes selected from soybeans, peas, and mung beans, germinated beans germinated from the legumes, or combinations thereof. In addition, the extract of the natural product containing coumestrol is obtained by completely concentrating the extract obtained by cold-soaking or warm-soaking the natural product containing coumestrol in 70% ethanol at room temperature, and then dispersing it again in water and fractionating it with one or more solvents selected from hexane, dichloromethane, chloroform, ethyl acetate, butanol, ethanol, methanol, and water to obtain an extract of the natural product containing coumestrol. However, the extraction method is not limited thereto, and all extraction methods that can ensure the inclusion of coumestrol in the final extract can be used.

[0032] Coumestrol in the composition may be included in a concentration range of 0.001 μM to 1,000 μM, for example, a concentration range of 0.001 μM to 100 μM. When coumestrol is used at a concentration less than 0.001 μM, the effects of epidermal keratinocyte proliferation and migration are negligible and the skin barrier function improvement effect cannot be achieved. When coumestrol is used at a concentration exceeding 1,000 μM, cytotoxicity appears and it may be harmful to the human body, so it is not preferable.

[0033] The "pharmaceutically effective amount" refers to an amount sufficient for the bioactive ingredient to exhibit the intended physiological or pharmacological activity when administered to an animal or a human. However, the pharmaceutically effective amount can be appropriately varied depending on the degree of the symptom, the age, weight, health status, gender, administration route, and treatment period of the patient.

[0034] In addition, the term "pharmaceutically acceptable" means that when administered to humans physiologically acceptable, it generally does not cause gastrointestinal disorders, allergic reactions such as dizziness or similar reactions. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. Further, it can additionally contain fillers, anticoagulants, lubricants, wetting agents, fragrances, emulsifiers and preservatives, etc.

[0035] For example, the composition can be a cosmetic composition.

[0036] As used herein, "cosmetics" can mean all substances that can have not only beauty functions but also additional medical functions other than beauty functions.

[0037] The dosage form of the cosmetic composition is not particularly limited and can be appropriately selected according to the intended purpose.

[0038] For example, the cosmetic composition can be formulated into solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansers, oils, powder foundations, emulsion foundations, wax foundations, and sprays, etc., but is not limited thereto. More specifically, cosmetic compositions such as detergents, tonics, hair styling agents, nutritive lotions, essences, serums, treatments, conditioners, shampoos, lotions, hair nourishing agents or hair dyes, water-in-oil (O / W) type, oil-in-water ( W / O ) It can be formulated into a basic cosmetic such as a [specific dosage form]. In addition, in each dosage form of the composition, other components in addition to the essential components can be selected and formulated by those skilled in the art without difficulty according to the type of other external preparations or the purpose of use. For example, it can further contain a sunscreen agent, a hair conditioning agent, a fragrance, etc.

[0039] The cosmetic composition can contain a cosmetically acceptable medium or base. This is suitable for all dosage forms suitable for topical application, for example, solutions, gels, solid or anhydrous products obtained by kneading, emulsions obtained by dispersing an oil phase in an aqueous phase, suspensions, microemulsions, microcapsules, fine granulocytes or in the form of ionic (liposomes) and / or non-ionic vesicles dispersants, or in the form of creams, skins, lotions, powders, ointments, sprays or concealer sticks. These compositions can be manufactured by conventional methods in the art.

[0040] When the dosage form of the present invention is a solution or an emulsion, as a carrier component, a solvent, a solubilizing agent or an emulsifying agent is used. For example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol fatty acid ester, polyethylene glycol or sorbitan fatty acid ester.

[0041] When the dosage form of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth can be used.

[0042] When the dosage form of the present invention is a paste, cream or gel, as the carrier component, animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicon, bentonite, silica, talc or zinc oxide can be used.

[0043] When the dosage form of the present invention is a powder or spray, as the carrier component, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder can be used. Particularly when it is a spray, a propellant such as chlorofluorohydrocarbon, propane / butane or dimethyl ether can additionally be included.

[0044] In one embodiment of the present invention, a thickener can additionally be contained in the cosmetic composition. The thickeners contained in the cosmetic composition of the present invention can be methyl cellulose, carboxymethyl cellulose, carboxymethyl hydroxyguanine, hydroxymethyl cellulose, hydroxyethyl cellulose, carboxyvinyl polymer, polyquaternium, cetearyl alcohol, stearic acid, carrageenan, etc. Preferably, one or more of carboxymethyl cellulose, carboxyvinyl polymer, and polyquaternium can be used, and most preferably, it can be carboxyvinyl polymer.

[0045] In one embodiment of the present invention, the cosmetic composition can contain various appropriate bases and additives as needed, and the types and amounts of these components can be easily selected by the inventor. Permissible additives can be contained as needed. For example, components such as preservatives, pigments, and additives that are common in the industry can be additionally included.

[0046] Specifically, the preservative may be phenoxyethanol or 1,2 - hexanediol, etc., and the fragrance may be an artificial fragrance, etc.

[0047] And in one embodiment of the present invention, the cosmetic composition can include a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high-molecular peptides, high-molecular polysaccharides, sphingolipids, and seaweed extracts. As other optional compounding ingredients, there may be mentioned oil and fat components, humectants, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, blood circulation promoters, cooling agents, antiperspirants, purified water, and the like.

[0048] Moreover, the other optional compounding ingredients are not limited to these, and any of the above ingredients can be compounded as long as the object and effect of the present invention are not impaired.

[0049] Furthermore, the cosmetic composition according to one embodiment can be used not only as a pharmaceutical composition as described above, but also as a health functional food. For example, it can be easily utilized as a main raw material, auxiliary raw material, food additive, functional food, or beverage of food.

[0050] The "food" means a natural product or processed product containing one or more nutrients, preferably a product that has undergone a certain degree of processing and can be directly eaten, and in the ordinary sense, it refers to a product that includes all foods, food additives, functional foods, and beverages.

[0051] Examples of foods to which the food composition can be added include various foods, beverages, gums, teas, vitamin complexes, functional foods, etc. Additionally, special nutritional foods (e.g., prepared milk products, infant foods, etc.), processed meat products, fish products, tofu products, mucilaginous foods, noodles (e.g., ramen, soba, etc.), breads, health supplements, seasoned foods (e.g., soy sauce, miso, kochujang, mixed sauces, etc.), sauces, confectioneries (e.g., snacks), candies, chocolates, gums, ice creams, dairy processed products (e.g., fermented milk, cheese, etc.), other processed foods, kimchi, salted foods (various kimchis, janachi, etc.), beverages (e.g., fruit beverages, vegetable beverages, soy milk, fermented beverages, etc.), natural seasonings (e.g., ramen soup, etc.), but are not limited thereto. The above foods, beverages, or food additives can be manufactured by ordinary manufacturing methods.

[0052] Also, the "functional food" or "health functional food" means a group of foods or food compositions to which added value is imparted by using physical, biochemical, biotechnological methods, etc. to make the functions of the food act and be expressed for specific purposes, and foods designed and processed so that the in-vivo regulatory functions related to biological defense rhythm regulation, disease prevention and recovery, etc. are fully expressed in the living body, and specifically, they can be health functional foods. The functional foods can include food auxiliaries and additives acceptable in food science, and can further include appropriate carriers, excipients, and diluents commonly used in the manufacture of functional foods.

[0053] Examples of the types of the health supplements can be, but are not limited to, powder, granule, tablet, capsule, or beverage form.

[0054] According to another embodiment, there is provided a method of inhibiting cortisone reductase by applying to the skin a composition containing, as an active ingredient, an effective amount of coumestrol extracted from beans.

[0055] The advantages, features, and the methods for achieving them of the present invention should become clear by referring to the examples described in detail later. Hereinafter, the present invention will be described in detail by way of examples. However, these examples are for specifically explaining the present invention, and the scope of the present invention is not limited to these examples.

[0056] [Example] Test Example 1: Inhibitory effect of coumestrol on cortisone reductase activity Normal human epidermal keratinocytes (NHEK) were cultured in a 6-well plate incubator. After 24 hours, they were irradiated with UVB (25 mJ / cm 2 ) alternately with phosphote-buffered saline (PBS), and cortisone (10 μM) was added to the NHEK culture medium without hydrocortisone and cultured for 4 days. Then, the cell culture fluid was collected, and the cortisol concentration was measured using the ELISA method. The results are shown in Fig. 1. Referring to Fig. 1, it can be confirmed that the cortisol concentration increases significantly in the wells with cortisone added after UV irradiation (UVB 25 mJ / cm 2 ) compared to before UV irradiation (CON; CONTROL). However, when the well contains coumestrol (1 μM, 5 μM, 10 μM), it can be confirmed that the cortisol concentration does not increase significantly. From this, it can be confirmed that the composition according to one embodiment containing coumestrol as an active ingredient inhibits the activity of 11β-hydroxysteroid dehydrogenase type 1, which is a cortisone reductase.

[0057] Test Example 2: Inhibitory effect of coumestrol on cortisone reductase activity In addition, the human keratinocytes were separated for proteins using RIPA lysis buffer, and the protein expressions of keratinocyte differentiation markers (KRT1, Filaggrin) were confirmed through Western blotting. The results are shown in FIGS. 2 and 3 below. Referring to FIGS. 2 and 3, in the case of the wells containing coumestrol (1 μM, 5 μM, 10 μM), it can be confirmed that the gene expressions of the keratinocyte differentiation markers (KRT1, Filaggrin), which were inhibited by ultraviolet rays (UVB) in keratinocytes, are increased. That is, it can be understood that the gene expressions of the keratinocyte differentiation markers, which were inhibited by ultraviolet rays (UVB) in keratinocytes, are restored by coumestrol, and it can be inferred from this that the gene expressions of the said keratinocyte differentiation markers were restored by coumestrol inhibiting the cortisone reductase activity and decreasing the cortisone concentration.

[0058] The preferred embodiments of the present invention have been described in detail above. However, the scope of the rights of the present invention is not limited thereto, and various modifications and improvements by those skilled in the art using the basic concept of the present invention defined in the following claims also belong to the scope of the rights of the present invention.

Claims

1. A composition for inhibiting 11β-hydroxysteroid dehydrogenase type 1, comprising cumestrol as an active ingredient.

2. The composition for inhibiting 11β-hydroxysteroid dehydrogenase type 1 according to Claim 1, wherein the cumestrol is contained in a concentration range of 0.001 μM to 1,000 μM.

3. The composition for inhibiting 11β-hydroxysteroid dehydrogenase type 1 according to Claim 1, wherein the composition is a cosmetic composition.

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