WO2023149791A1 - 적소두 추출물을 유효성분으로 포함하는 염증성 부종 예방 및 치료용 조성물 - Google Patents
적소두 추출물을 유효성분으로 포함하는 염증성 부종 예방 및 치료용 조성물 Download PDFInfo
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- WO2023149791A1 WO2023149791A1 PCT/KR2023/001759 KR2023001759W WO2023149791A1 WO 2023149791 A1 WO2023149791 A1 WO 2023149791A1 KR 2023001759 W KR2023001759 W KR 2023001759W WO 2023149791 A1 WO2023149791 A1 WO 2023149791A1
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- edema
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Images
Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/326—Foods, ingredients or supplements having a functional effect on health having effect on cardiovascular health
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/21—Plant extracts
Definitions
- the present invention provides a composition for preventing and treating inflammatory edema comprising a red soybean extract as an active ingredient.
- Ederma refers to a condition in which tissue fluid accumulates between tissue cells in the body, and is simply a symptom of body swelling. It can be caused by heart disease, kidney disease, or poor circulation in any part of the body. In the case of the legs, in particular, because they are far from the heart and are greatly affected by gravity, blood flow to the kidneys is reduced, resulting in edema. In addition, in the case of women, edema occurs during normal pregnancy or pregnancy toxemia, and edema may appear temporarily when a lot of water or salt is consumed, or when fatigue or lack of sleep, but it subsides on its own. When capillary permeability increases, for example, local edema also occurs in the case of burns, trauma, local inflammation, allergic reactions, and the like.
- leg edema in the case of leg edema, it is easily perceived as a feeling of tight shoes because it is accompanied by edema of the feet and ankles.
- Systemic edema can be divided into cardiac, renal, hepatic, endocrine, and dystrophic edema, and local edema includes vascular and lymphatic occlusion and vasomotor edema.
- vascular and lymphatic occlusion and vasomotor edema When edema occurs, the body swells, weight increases, the eyes are swollen when waking up, the rings on the fingers are tight, and the shoes seem to be small.
- a hollow edema pitting edema
- Edema is known to accelerate blood circulation disorders and skin aging due to local excessive moisture in the skin. Skin problems are generally known to exacerbate the condition of people with lymphedema, where there is an overload and improper functioning of the lymphatic system.
- vascular permeability In addition, one of the important early symptoms of inflammation is the enhancement of vascular permeability.
- vascular permeability There are two aspects of this vascular permeability: a transient immediate response and a delayed response.
- the immediate reaction is promoted by amines such as histamine and enhances venous permeability.
- the delayed reaction has a long-term effect on permeability enhancement in peptides that are free from inflammatory tissues, liquid components in the plasma leak out of the blood vessels and are stored in the inflammatory area.
- edema is called inflammatory edema.
- This edema fluid is rich in protein, has a heavy specific gravity, and contains many cellular components such as white blood cells.
- Phaseolus angularis Wight has eight valleys in the Book of Poetry: Seo ( ⁇ ), Jik ( ⁇ ), Do ( ⁇ ), Liang ( ⁇ ), Hua ( ⁇ ), Ma ( ⁇ ), and Shu ( They were called maek ( ⁇ ) and maek ( ⁇ ), and among them, suk refers to soybean (large bean) and small bean (small bean) is called dab, and they are said to have distinguished each other.
- red bean, white bean, and mung bean are all called sodu, but especially red bean is small and red that is used in medicine, so it means red bean now, and it has diuretic and anti-inflammatory properties.
- the inventors of the present invention have made intensive efforts to develop a composition containing a natural extract that has a preventive or therapeutic effect on inflammatory edema and has no side effects, and as a result, it was confirmed that the red soybean extract suppresses inflammation and edema, thereby completing the present invention.
- An object of the present invention is to provide a food composition for preventing and improving edema comprising red soybean extract as an active ingredient.
- An object of the present invention is to provide a pharmaceutical composition for preventing and treating edema, comprising an extract of red soybean as an active ingredient.
- An object of the present invention is to provide a cosmetic composition for preventing and improving edema, comprising red soybean extract as an active ingredient.
- An object of the present invention is to provide a method for preventing and treating edema, which includes administering to a subject a pharmaceutical composition for preventing and treating edema, which includes a pharmaceutically effective amount of a red soy bean extract as an active ingredient.
- An object of the present invention is to prevent edema comprising administering to a subject a food composition for preventing and improving edema containing an effective amount of an extract of red soybean as an active ingredient or a cosmetic composition for preventing and improving edema containing an extract of red soybean as an active ingredient. and to provide improvement methods.
- the present invention provides a food composition for preventing and improving edema comprising a red soybean extract as an active ingredient.
- the present invention provides a pharmaceutical composition for preventing and treating edema, comprising an extract of red soybean as an active ingredient.
- the present invention provides a cosmetic composition for preventing and improving edema comprising a red soy bean extract as an active ingredient.
- the present invention provides a method for preventing and treating edema, comprising administering to a subject a pharmaceutical composition for preventing and treating edema containing a pharmaceutically effective amount of a red soybean extract as an active ingredient.
- the present invention provides a food composition for preventing and improving edema containing an effective amount of an extract of red soybean as an active ingredient or a cosmetic composition for preventing and improving edema containing an extract of red soybean as an active ingredient to prevent and improve edema comprising administering to a subject. provides a way
- the red soybean extract of the present invention causes an inflammatory reaction by administering LPS to an animal model, and then administering the red soybean extract of the present invention, IL-1 beta mRNA, IL-6 mRNA, TNF- It was confirmed that it inhibits alpha and IL-4. In addition, IL-10 expression involved in the early inflammatory reaction was increased and IL-18 involved in the acquired immune response was suppressed, and swelling of the soles of animal models was also visually reduced, and infiltrating cells in the sole tissues were reduced. Confirmed. Bar, confirming that it is effective in improving and treating inflammatory edema, it can be used for useful projects related to inflammatory edema.
- FIG. 1 is a diagram showing mRNA sequence numbers of IL-6, IL-1 beta, TNF-alpha, IL-4, IL-10 and IL-18.
- Figure 2 is a diagram showing the foot size (height and width sum) of the mouse model by administering the red soybean extract of the mouse model in which skin edema was induced by the administration of LPS.
- Figure 3 is a diagram showing the inhibition of IL-1 beta mRNA expression by administering the red soybean extract of a mouse model in which skin edema was induced by LPS administration.
- Figure 4 is a diagram showing the inhibition of mRNA expression of IL-6 by administering the red soybean extract of a mouse model in which skin edema was induced by the administration of LPS.
- Figure 5 is a diagram showing the inhibition of the increase in mRNA expression of TNF-alpha by administering the extract of red soybean in a mouse model in which skin edema was induced by the administration of LPS.
- FIG. 6 is a diagram showing the blocking of IL-4 mRNA expression level by administering the red soy bean extract of a mouse model in which skin edema was induced by LPS administration.
- FIG. 7 is a diagram showing that the expression level of IL-10 mRNA was significantly high by administering the red soybean extract of a mouse model in which skin edema was induced by the administration of LPS.
- FIG. 8 is a diagram showing the blocking of the increase in IL-18 mRNA expression by administering the red soy bean extract in a mouse model in which skin edema was induced by the administration of LPS.
- FIG. 9 is a diagram showing the appearance of suppression of edema of the soles of the mouse model by administering the extract of red soybean in a mouse model in which skin edema was induced by the administration of LPS.
- FIG. 10 is a diagram showing the effect of reducing infiltrating cells in footpad tissue of a mouse model by administering the red soybean extract of a mouse model in which skin edema was induced by the administration of LPS.
- terminal used in this specification are terms used to appropriately express preferred embodiments of the present invention, which may vary according to the intention of a user or operator or customs in the field to which the present invention belongs. Therefore, definitions of these terms will have to be made based on the content throughout this specification. Throughout the specification, when a certain component is said to "include”, it means that it may further include other components without excluding other components unless otherwise stated.
- the present invention provides a food composition for preventing and improving edema comprising a red soybean extract as an active ingredient.
- the food composition of the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients like conventional food compositions.
- natural carbohydrates examples include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrins and cyclodextrins, and sugar alcohols such as xylitol, sorbitol and erythritol.
- natural flavoring agents thaumatin
- stevia extracts eg rebaudioside A, glycyrrhizin, etc.
- synthetic flavoring agents sacharin, aspartame, etc.
- the food composition of the present invention can be formulated in the same way as the pharmaceutical composition and used as a functional food or added to various foods.
- Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gum, candy, ice cream, alcoholic beverages, vitamin complexes and health supplements, etc. there is
- the food composition in addition to the active ingredient extract, various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, Alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like may be contained.
- the food composition of the present invention may contain fruit flesh for preparing natural fruit juice, fruit juice beverages, and vegetable beverages.
- the functional food composition of the present invention may be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills, and the like.
- 'health functional food composition' refers to a food manufactured and processed using raw materials or ingredients having useful functionality for the human body according to Health Functional Food Act No. 6727, and the structure and function of the human body It refers to intake for the purpose of obtaining useful effects for health purposes such as regulating nutrients or physiological functions.
- the health functional food of the present invention may contain ordinary food additives, and the suitability as a food additive is determined according to the general rules of the Food Additive Code and General Test Methods approved by the Food and Drug Administration, unless otherwise specified. It is judged according to standards and standards.
- Examples of the items listed in the 'Food Additive Code' include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon pigment, licorice extract, crystalline cellulose, kaoliang pigment, and guar gum; and mixed preparations such as sodium L-glutamate preparations, noodle-added alkali preparations, preservative preparations, and tar color preparations.
- chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid
- natural additives such as persimmon pigment, licorice extract, crystalline cellulose, kaoliang pigment, and guar gum
- mixed preparations such as sodium L-glutamate preparations, noodle-added alkali preparations, preservative preparations, and tar color preparations.
- a health functional food in the form of a tablet is obtained by granulating a mixture obtained by mixing the active ingredient of the present invention with an excipient, a binder, a disintegrant, and other additives in a conventional manner, and then adding a lubricant or the like to compression molding, or as described above.
- the mixture can be directly compression molded.
- the health functional food in the form of a tablet may contain a flavoring agent and the like as needed.
- hard capsules can be prepared by filling a mixture in which the active ingredient of the present invention is mixed with additives such as excipients in a normal hard capsule. It can be prepared by filling the mixture mixed with gelatin in a capsule base.
- the soft capsule may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary.
- a plasticizer such as glycerin or sorbitol
- a colorant such as a preservative, and the like
- the health functional food in the form of a pill can be prepared by molding a mixture of the active ingredient of the present invention mixed with an excipient, a binder, a disintegrant, etc. by a conventionally known method, and can be coated with sucrose or other coating agent if necessary, Alternatively, the surface may be coated with a material such as starch or talc.
- Health functional food in the form of granules can be prepared in granular form by a conventionally known method of mixing the active ingredient of the present invention with excipients, binders, disintegrants, etc., and, if necessary, flavoring agents, flavoring agents, etc. can
- Pretanol A is a vegetable ethanol made from alcohol, and is commonly used for sterilization and cleaning of medical and food companies, and is widely used in natural diffusers and mosquito repellents.
- Pretanol A suppresses germs that spoil food and impairs its freshness, so it is used to improve preservation during food processing, and 95% of Pretanol A is used for soaps and cosmetics that use anhydrous alcohol.
- the edema is at least one from the group consisting of inflammatory edema, idiopathic edema, edema due to heart failure, edema due to kidney disease, edema due to vascular abnormalities such as lymphatics and veins, and inflammatory edema due to surgery and plastic surgery, but preferably is an inflammatory edema due to surgical and plastic surgery.
- the red soybean extract may be extracted with any one solvent selected from the group consisting of water, C1 to C4 lower alcohol, or a mixed solvent thereof, but is not limited thereto, but is preferably pretanol A.
- composition reduces IFN-gamma, but is not limited thereto.
- composition inhibits the expression of IL-1 beta, IL-6, TNF-alpha, IL-4 and IL-18, but is not limited thereto.
- composition increases IL-10 expression, but is not limited thereto.
- composition reduces infiltration of inflammatory cells, but is not limited thereto.
- the red soy bean extract is 0 to 400 mg/kg, preferably 100 to 300 mg/kg.
- the present invention provides a pharmaceutical composition for preventing and treating edema, comprising an extract of red soybean as an active ingredient.
- the pharmaceutical composition of the present invention may further include an adjuvant in addition to the active ingredient.
- an adjuvant in addition to the active ingredient.
- any one may be used without limitation, but, for example, Freund's complete adjuvant or incomplete adjuvant may be further included to increase immunity.
- the pharmaceutical composition according to the present invention may be prepared in the form of incorporating the active ingredient into a pharmaceutically acceptable carrier.
- the pharmaceutically acceptable carrier includes carriers, excipients and diluents commonly used in the pharmaceutical field.
- Pharmaceutically acceptable carriers usable in the pharmaceutical composition of the present invention include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
- the pharmaceutical composition of the present invention may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories or sterile injection solutions according to conventional methods, respectively. .
- Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations contain at least one or more excipients such as starch, calcium carbonate, sucrose, lactose, and gelatin in addition to active ingredients. It can be prepared by mixing etc. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.
- Liquid preparations for oral administration include suspensions, solutions for oral administration, emulsions, syrups, etc.
- compositions for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations and suppositories.
- Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents.
- a base for suppositories witepsol, tween 61, cacao paper, laurin paper, glycerogelatin, and the like may be used.
- composition according to the present invention can be administered to a subject by various routes. All modes of administration are contemplated, eg oral, intravenous, intramuscular, subcutaneous, intraperitoneal injection.
- the dosage of the pharmaceutical composition according to the present invention is selected in consideration of the age, weight, sex, and physical condition of the subject. It is obvious that the concentration of the active ingredient included in the pharmaceutical composition can be variously selected according to the subject, and is preferably included in the pharmaceutical composition at a concentration of 0.01 to 5,000 ⁇ g/ml. If the concentration is less than 0.01 ⁇ g/ml, pharmacological activity may not appear, and if the concentration exceeds 5,000 ⁇ g/ml, toxicity to the human body may be exhibited.
- the pharmaceutical composition may be formulated into various oral or parenteral dosage forms.
- Formulations for oral administration include, for example, tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, granules, etc. chlorose, mannitol, sorbitol, cellulose and/or glycine), lubricants such as silica, talc, stearic acid and magnesium or calcium salts thereof and/or polyethylene glycol.
- the tablet may contain a binder such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, and in some cases starch, agar, alginic acid or a disintegrant or effervescent mixture, such as its sodium salt, and/or absorbents, colorants, flavors, and sweeteners.
- a binder such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, and in some cases starch, agar, alginic acid or a disintegrant or effervescent mixture, such as its sodium salt, and/or absorbents, colorants, flavors, and sweeteners.
- the formulation may be prepared by conventional mixing, granulating or coating methods.
- a typical formulation for parenteral administration is an injection formulation, and water, Ringer's solution, isotonic physiological saline or suspension may be used as a solvent for the injection formulation.
- Sterile fixed oils of the above injectable preparations may be used as a solvent or suspending medium, and any bland fixed oil may be used for this purpose, including mono- and di-glycerides.
- the formulation for injection may use a fatty acid such as oleic acid.
- composition of the present invention can be variously used for preventing or improving skin diseases caused by antibiotic-resistant bacteria.
- Products to which this composition can be added include, for example, cosmetics such as various creams, lotions, toners, and essences, shampoos, rinses, cleansing products, face wash products, soaps, treatments, packs, beauty essences, and the like.
- the present invention provides a cosmetic composition for preventing and improving edema containing an extract of Phaseolus angularis Wight as an active ingredient.
- the cosmetic composition of the present invention includes a composition selected from the group consisting of water-soluble vitamins, fat-soluble vitamins, high-molecular peptides, high-molecular polysaccharides, sphingolipids, and seaweed extracts.
- Any water-soluble vitamin can be used as long as it can be formulated into cosmetics, but preferably vitamin B1, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, vitamin H, etc. salts (thiamin hydrochloride, sodium ascorbate, etc.) or derivatives (sodium ascorbic acid-2-phosphate, magnesium salt of ascorbic acid-2-phosphate, etc.) included Water-soluble vitamins can be obtained by conventional methods such as a microbial transformation method, a purification method from a microbial culture, an enzymatic method, or a chemical synthesis method.
- Any fat-soluble vitamin can be used as long as it can be formulated into cosmetics, but preferably vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol), etc. are mentioned. , their derivatives (ascorbine palmitate, ascorbine stearate, ascorbine dipalmitate, dl-alpha tocopherol acetate, dl-alpha tocopherol nicotinate, vitamin E, DL-pantothenyl alcohol, D-pantothenyl alcohol, pantothenylethyl ether, etc.) and the like are also included in the fat-soluble vitamins used in the present invention. Fat-soluble vitamins can be obtained by conventional methods such as a microbial transformation method, a purification method from a microbial culture, an enzymatic or chemical synthesis method, and the like.
- Any polymeric peptide may be used as long as it can be formulated into cosmetics, but preferably collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, keratin and the like are mentioned.
- Polymer peptides can be purified and obtained by conventional methods such as a purification method from a culture medium of microorganisms, an enzyme method, or a chemical synthesis method, or can be used after being purified from natural products such as pig or cow dermis or silkworm silk fibers.
- Any polymeric polysaccharide may be used as long as it can be incorporated into cosmetics, but hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate or a salt thereof (sodium salt or the like) is preferable.
- chondroitin sulfate or a salt thereof can be used after being purified from mammals or fish.
- sphingolipid can be used as long as it can be incorporated into cosmetics, but ceramide, phytosphingosine, sphingoglycolipid and the like are preferred. Sphingolipids can be purified by conventional methods or obtained by chemical synthesis from mammals, fish, shellfish, yeast, or plants.
- the cosmetic composition of the present invention may also contain other ingredients commonly used in cosmetics, if necessary.
- Other ingredients that may be added include fats and oils, humectants, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, A blood circulation accelerator, a cooling agent, an antiperspirant, purified water, etc. are mentioned.
- the oil and fat component include ester oils, hydrocarbon oils, silicone oils, fluorine oils, animal fats and vegetable oils.
- ester-based fats and oils As ester-based fats and oils, triglyceryl 2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isostearate isocetyl, stearic acid Butyl, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, adipine Diisopropyl acid, isoalkyl neopentanoate, tri(capryl, capric acid) glyceryl, trimethylo
- hydrocarbon-based fats and oils examples include hydrocarbon-based fats and oils such as squalene, liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybuden, microcrystalline wax, and vaseline.
- silicone oils include polymethylsilicone, methylphenylsilicone, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane and methylcetyloxysiloxane copolymers, dimethylsiloxane and methylstealoxysiloxane copolymers, alkyl Modified silicone oil, amino modified silicone oil, etc. are mentioned.
- fluorine-based fats and oils examples include perfluoropolyether and the like.
- Animal or vegetable oils include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, birdflower oil, soybean oil, corn oil, rapeseed oil, algae oil, palm kernel oil, palm oil, castor oil, sunflower oil, grape seed oil , cottonseed oil, palm oil, kukui nut oil, wheat germ oil, rice germ oil, shea butter, moonshine colostrum, marker damian nut oil, meadowsweet oil, egg yolk oil, beef tallow, horse oil, mink oil, orange raffia oil, jojoba oil , animal or plant fats and oils such as candelilla wax, carnaba wax, liquid lanolin, and hydrogenated castor oil.
- avocado oil almond oil, olive oil, sesame oil, rice bran oil, birdflower oil, soybean oil, corn oil, rapeseed oil, algae oil, palm kernel oil, palm oil, castor oil, sunflower oil, grape seed oil , cottonseed oil, palm oil, kukui nut oil, wheat germ
- moisturizer examples include water-soluble low-molecular moisturizers, fat-soluble molecular moisturizers, water-soluble polymers, and oil-soluble polymers.
- Cholesterol, cholesterol ester, etc. are mentioned as a fat-soluble low-molecular moisturizer.
- water-soluble polymers include carboxyvinyl polymer, polyaspartate, tragacanth, xanthan gum, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, water-soluble chitin, chitosan, dextrin, and the like.
- the fat-soluble polymers include polyvinylpyrrolidone and eicosene copolymers, polyvinylpyrrolidone and hexadecene copolymers, nitrocellulose, dextrin fatty acid esters, and high-molecular silicones.
- the emollient agent include long-chain acyl glutamic acid cholesteryl ester, hydroxystearic acid cholesteryl, 12-hydroxystearic acid, stearic acid, rosin acid, and lanolin fatty acid cholesteryl ester.
- surfactant examples include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants.
- Nonionic surfactants include self-emulsifying glycerin monostearate, propylene glycol fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, POE (polyoxyethylene) sorbitan fatty acid esters, POE sorbitan fatty acid esters, POE Glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hydrogenated castor oil, POE castor oil, POE and POP (polyoxyethylene and polyoxypropylene) copolymer, POE and POP alkyl ether, polyether modified silicone, lauric acid alkanolamides, alkylamine oxides, hydrogenated soybean phospholipids, and the like.
- Anionic surfactants include fatty acid soaps, alpha-acyl sulfonates, alkyl sulfonates, alkyl allyl sulfonates, alkyl naphthalene sulfonates, alkyl sulfates, POE alkyl ether sulfates, alkyl amide sulfates, alkyl phosphates, POE alkyl phosphates, alkyl amides.
- alkyloylalkyl taurine salts N-acylamino acid salts
- POE alkyl ether carboxylates alkyl sulfosuccinates, sodium alkyl sulfoacetates, acylated hydrolyzed collagen peptide salts, perfluoroalkyl phosphate esters, and the like. there is.
- Amphoteric surfactants include carboxybetaine type, amidebetaine type, sulfobetaine type, hydroxysulfobetaine type, amide sulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amideamine type, etc. An amphoteric surfactant etc. are mentioned.
- organic and inorganic pigments silicic acid, silicic anhydride, magnesium silicate, talc, sericite, mica, kaolin, bengala, clay, bentonite, titanium-coated mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, aluminum oxide inorganic pigments such as calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, ultramarine blue, chromium oxide, chromium hydroxide, calamine and complexes thereof; polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenolic resin, fluororesin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, divinylbenzene and styrene copolymers, organic pigments such as silk powder, cellulose, CI pigment yellow and CI pigment orange, and composite pigments of these
- organic powder examples include metal soaps such as calcium stearate; Alkyl phosphate metal salts, such as zinc sodium cetylrate, zinc laurylrate, and calcium laurylrate; polyvalent metal salts of acyl amino acids such as N-lauroyl-beta-alanine calcium, N-lauroyl-beta-alanine zinc, and N-lauroyl glycine calcium; polyvalent metal salts of amide sulfonic acids such as N-lauroyl-taurine calcium and N-palmitoyl-taurine calcium; N-epsilon-lauroyl-L-lysine, N-epsilon-palmitoylizine, N-alpha-paritoylolnithine, N-alpha-lauroylarginine, N-alpha-hardened beef fatty acid acylarginine, etc.
- metal soaps such as calcium stearate
- Alkyl phosphate metal salts such
- N-acyl basic amino acids such as N-lauroylglycylglycine
- alpha-amino fatty acids such as alpha-aminocaprylic acid and alpha-aminolauric acid
- polyethylene polypropylene, nylon, polymethyl methacrylate, polystyrene, divinylbenzene and styrene copolymers, tetrafluoroethylene, and the like.
- UV absorbers examples include para-aminobenzoic acid, ethyl para-aminobenzoate, amyl para-aminobenzoate, octyl para-aminobenzoate, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomenthyl salicylate, and benzyl cinnamate.
- Bactericides include hinokitiol, triclosan, trichlorohydroxydiphenyl ether, chlorhexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid, zincophylthione, benzalkonium chloride, photosensitizer So No. 301, mononitroguacol sodium, undecyrenic acid, etc. are mentioned.
- antioxidants examples include butylhydroxyanisole, propyl gallic acid, and elisorbic acid.
- pH adjuster examples include citric acid, sodium citrate, malic acid, sodium malate, fumaric acid, sodium fumalate, succinic acid, sodium succinate, sodium hydroxide, and sodium monohydrogenphosphate.
- alcohol examples include higher alcohols such as cetyl alcohol.
- blending components that may be added other than these are not limited thereto, and any of the above components can be blended within a range not impairing the objects and effects of the present invention.
- the cosmetic composition of the present invention may take the form of a solution, emulsion, viscous mixture or the like.
- Ingredients included in the cosmetic composition of the present invention may include ingredients commonly used in cosmetic compositions as active ingredients, for example, stabilizers, solubilizers, conventional adjuvants and carriers such as vitamins, pigments and flavors. include
- the cosmetic composition of the present invention may be prepared in any formulation conventionally prepared in the art, and examples thereof include emulsion, cream, lotion, pack, foundation, lotion, beauty essence, hair cosmetics, and the like.
- the cosmetic composition of the present invention is skin lotion, skin softener, skin toner, milk lotion, astringent, lotion, moisture lotion, nutrient lotion, massage cream, nutrient cream, moisture cream, hand cream, foundation, essence, nutrient essence, It includes 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.
- the formulation of the present invention is a paste, cream or gel, animal fiber, vegetable fiber, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component.
- lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, additional chlorofluorohydrocarbon, propane / May contain a propellant such as butane or dimethyl ether.
- a solvent, solvating agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butyl glycol oil, fatty acid esters of glycerol, polyethylene glycol or sorbitan.
- the formulation of the present invention is a suspension
- a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline Cellulose, aluminum metahydroxide, bentonite, agar or tracanth and the like may be used.
- the formulation of the present invention is surfactant-containing cleansing
- carrier components aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide ether Sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolin derivatives, or ethoxylated glycerol fatty acid esters may be used.
- the present invention provides a method for preventing and treating edema, comprising administering to a subject a pharmaceutical composition for preventing and treating edema containing a pharmaceutically effective amount of a red soy bean extract as an active ingredient.
- the present invention provides a method for preventing and treating edema comprising administering to a subject a pharmaceutical composition for preventing and treating edema comprising a pharmaceutically effective amount of the red soy bean extract as an active ingredient.
- the pharmaceutical composition of the present invention is administered in a therapeutically effective amount or a pharmaceutically effective amount.
- pharmaceutically effective amount means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is dependent on the type and severity of the subject, age, sex, activity of the drug, and drug. sensitivity, time of administration, route of administration and excretion rate, duration of treatment, factors including concomitantly used drugs, and other factors well known in the medical field.
- Preparation example 1 mRNA analysis of inflammatory mediators and related factors related to edema.
- cDNA was synthesized and reacted with specific primers shown in Figure 1 below to obtain IL-6, IL-1 beta, TNF-alpha, IL-4, IL-10 and IL-18 mRNA sequences were investigated (FIG. 1).
- the red small head of this experiment was purchased from a herbal medicine wholesaler in Gwangmyeongdang, and the experiment was conducted. Put 500g of red beans into a non-woven fabric, fill 10 times (5 L) of Pretanol A 25%, and use a reflux extractor (MS-609, Korea) to extract twice at 80°C for 3 hours, then use a large rotary vacuum concentrator (Eyela, CA) -2600-chiller equipped with Eyela, NVC-2200, Japan) was used, and a standard extract of around 10 brix was prepared by concentrating at 30 hPa at 55 °C.
- the extract was frozen at -70 ° C using a deep freezer (Themo Scientific, TSE600D, USA), transferred to a lyophilizer (LYOPH-PRIDE 20R as Solutionshin, Bondi) and freeze-dried. After 124 hours, 53 g (10.6%) of the extract was obtained from the lyophilizer terminated.
- Example 2 The effect of inhibiting edema of red soybean extract was confirmed by the appearance of the foot size.
- red soybean extract of the present invention After oral administration of the red soybean extract of the present invention at concentrations of 100, 200 and 300 mg/kg for a week, 200 ng/paw LPS was administered to reduce skin swelling in order to create a model for edema and inflammation caused by plastic surgery and procedures. The appearance of the soles of the feet of the mouse model was confirmed to see if edema could be improved in the induced mouse model.
- Edema formation is caused by the infiltration of inflammatory cells and the accumulation of inflammatory substances, and LPS is known to cause edema of skin tissue in a skin inflammatory reaction. Therefore, in the mouse model in which skin edema was induced by LPS administration, negative control (0.84 ⁇ 0.04 cm), normal control (0.64 ⁇ 0.04 cm), positive control (0.64 ⁇ 0.04 cm), Red soy bean extract was administered at 100 (0.765 ⁇ 0.04 cm), 200 (0.735 ⁇ 0.03 cm), and 300 (0.660 ⁇ 0.04 cm) mg/kg, respectively.
- IFN-gamma has antiviral action and is a major factor involved in inflammatory response. It directly activates macrophages or promotes the differentiation of cytotoxic T cells. In addition, LPS increases IFN-gamma expression and plays a role in inflammatory response. Not only is it involved in the early stage of tissue edema formation by the skin, but it also reduces the skin's protective function by reducing long-chain fatty acids and ceramides in the skin.
- the red soybean extract of the present invention may be involved in the initial reaction of edema formation.
- IL-1 beta directly induces the secretion of inflammatory mediators in skin cells, increases the inflammatory response, causes skin irritation, and induces skin diseases such as psoriasis and atopic dermatitis through the induced inflammatory response, and is effective in improving skin inflammation. It is a factor commonly used in evaluation.
- IL-6 is known to be involved in both skin inflammation and skin regeneration, and is induced by the inflammatory factors IL-1 and TNF-alpha in the early stage of skin inflammation, and is induced by epidermal cells, endothelial cells, stromal cells and macrophages of the skin. promotes the release of pro-inflammatory factors from In addition, IL-6 not only promotes the expression of matrix metalloproteinase (MMP) and decomposes the skin matrix under excessive inflammatory conditions, but also has a high response to inflammatory stimuli and has a high expression rate compared to other inflammatory factors, so it is important in the inflammatory response. treated as an argument
- the red soy bean extract of the present invention suppressed the mRNA expression of IL-6 beta from 200 mg/kg, and suppressed the mRNA expression of IL-6 beta (FIG. 4).
- TNF-alpha The expression level of TNF-alpha is increased in the skin inflammatory response caused by ultraviolet B (UVB), LPS or skin stimulation. In addition, it develops inflammatory activity, resulting in the expression of endothelial adhesion factor in the skin, participates in the infiltration of lymphocytes and circulation of T-lymphocytes, and aggregates leukocytes at the inflammatory site.
- UVB ultraviolet B
- the red soy bean extract of the present invention inhibited the mRNA expression of TNF-alpha from 200 mg / kg, and suppressed the mRNA expression of TNF-alpha in a concentration-dependent manner (FIG. 5).
- red soybean extract of the present invention After oral administration of the red soybean extract of the present invention at concentrations of 100, 200 and 300 mg/kg for a week, 200 ng/paw LPS was administered to reduce skin swelling in order to create a model for edema and inflammation caused by plastic surgery and procedures. It was confirmed whether IL-4 mRNA expression could be suppressed in the induced mouse model.
- IL-4 is known to mediate the action of reducing skin recovery and protective functions by regulating genes related to the epidermal differentiation complex in the skin inflammatory response caused by skin stimulation.
- IL-10 is an anti-inflammatory cytokine produced by various leukocytes.
- regulatory T cells have an immunosuppressive function through the secretion of IL-10, and suppress excessive immune responses to external antigens in the skin endothelium.
- IL-10 whose expression is increased by LPS, is known to regulate inflammatory shock in the early inflammatory response or directly oppose the production and action of inflammatory mediators such as nitric oxide.
- the group to which the red soy bean extract was orally administered had a significantly lower IL-10 mRNA expression level compared to the control group.
- red soy bean extract of the present invention acts at the beginning of the inflammatory response (FIG. 7).
- red soybean extract of the present invention After oral administration of the red soybean extract of the present invention at concentrations of 100, 200 and 300 mg/kg for a week, 200 ng/paw LPS was administered to reduce skin swelling in order to create a model for edema and inflammation caused by plastic surgery and procedures. It was confirmed whether IL-18 mRNA expression could be suppressed in the induced mouse model.
- IL-18 is a pro-inflammatory cytokine that induces the production of IFN-gamma and is involved in the activation of the inflammatory control complex, and is known to induce apoptosis by inducing the release of TNF-alpha in skin keratinocytes in the inflammatory response.
- the activated inflammatory regulatory complex induces inflammatory plaques by activating the NF-kB signaling pathway.
- Example 10 Inhibition of edema formation by red soybean extract and identification of infiltrating cells in tissues.
- red soybean extract of the present invention After oral administration of the red soybean extract of the present invention at concentrations of 100, 200 and 300 mg/kg for a week, 200 ng/paw LPS was administered to reduce skin swelling in order to create a model for edema and inflammation caused by plastic surgery and procedures.
- the soles of the feet of the induced mouse model were visually confirmed, and infiltrating cells of the soles of the feet were confirmed.
- LPS is known to cause edema of skin tissue in the skin inflammatory response.
- red soy bean extract of the present invention reduced swelling and inflammatory cells.
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Abstract
본 발명은 적소두 추출물을 유효성분으로 포함하는 외과 및 성형수술로 인한 염증성 부종 예방 및 치료용 조성물을 제공으로써, 본 발명의 적소두 추출물은 동물모델에 LPS를 투여하여 염증반응을 일으킨 후, 본 발명의 적소두 추출물을 투여하여, 염증 매개 물질 및 염증 반응에서 발현되는 IL-1 beta mRNA, IL-6 mRNA, TNF-alpha, IL-4를 억제시킴을 확인 하였다. 또한, 염증 초기반응에 관여하는 IL-10 발현을 증가 및 후천면역 반응에 관여하는 IL-18을 억제시고, 동물모델의 발바닥의 부종 또한 육안상 감소시켰으며, 발바닥 조직의 침윤세포 감소를 확인하였는 바, 염증성 부종 개선 및 치료에 효과적임을 확인하여, 염증성 부종과 관련된 유용한 사업에 사용될 수 있다.
Description
본 발명은 적소두 추출물을 유효성분으로 포함하는 염증성 부종 예방 및 치료용 조성물을 제공한다.
부종(Ederma)은 체내조직세포 사이에 조직액이 괸 상태를 가리키는 말로서, 간단히는 몸이 붓는 증상이다. 이는 심장병이나 신장병 또는 몸의 어느 한 부분의 혈액 순환 장애로 생길 수 있다. 다리의 경우는 특히 심장에서 거 리가 멀고 중력에 의한 영향이 크기 때문에 신장으로 가는 혈류가 줄어들어 부종이 생긴다. 또, 여자의 경우 정 상적인 임신 또는 임신중독증일때 부종이 발생하며, 수분이나 소금의 섭취를 많이 한 경우나 피로하거나 숙면을 취하지 못했을 때 일시적으로 부종이 나타날 수 있으나 저절로 가라앉는다. 모세혈관의 투과성이 증가하는 경우, 예를 들면 화상·외상·국소적 염증·알레르기 반응 등의 경우에도 국소부종이 발생한다.
특히 다리부종의 경우 발, 발목의 부종을 동반하므로 신발이 꽉 끼는 느낌으로 쉽게 자각할 수 있으며, 부종의 느낌과 함께 다리가 무거운 느낌을 동반하므로 몸전체의 피로를 다리부종으로 자각하게 되기도 한다. 전신적인 부종은 심장 성·신장성·간성·내분비성·영양장애성 부종으로 나눌 수 있고, 국소성 부종은 혈관·림프관의 폐색으로 인한 것과 혈관운동성 부종 등이 있다. 부종이 생기게 되면, 몸이 붓고, 체중이 증가하며, 자고 일어나면 눈이 붓고, 손가락의 반지가 꼭 끼고, 신발이 작아진 것 같다. 종아리 경골부위에 손가락으로 누르면 움푹 들어간 채우묵부종(함요부종)이 나타내기도 한다. 부종은 피부속의 국소적인 과다 수분으로 인한 혈액순환 장애 및 피부 노화를 촉진시키는 것으로 알려져 있다. 일반적으로 피부 문제는 임파계의 부적절한 기능과 과부하가 있는 임파 부종을 갖는 사람들의 상태를 더욱 악화시키는 것으로 알려져 있다.
또한, 염증 초기의 중요한 현상가운데 하나로 혈관투과성의 항진이 있다. 이 혈관투과성에는 일과성의 즉시반응과 지연반응의 2양상이 있다. 즉시반응은 히스타민 등의 아민류에 의해서 촉진되고 세정맥역의 투과성을 항진한다. 지연반응은 염증조직에서 유리하는 펩티드에서 투과성 항진에 장기작용하기때문에 혈장중의 액성성분이 혈관밖으로 누출해 염증부위에 저류한다. 이와같은 부종을 염증성 부종이라고 한다. 이 부종액은 단백성분이 풍부해 비중이 무겁고 백혈구 등의 세포성분을 많이 함유한다.
적소두(Phaseolus angularis Wight)는 기록에 의하면 시경에서 팔곡(八穀)을 서(黍), 직(稷), 도(稻), 량(粱), 화(禾), 마(麻), 숙(菽), 맥(麥)이라 하였는데 이 중에서 숙은 대두(大豆)를 말하며 소두(小豆)는 답이라고 하여 서로 구별하였다고 한다. 답 중에서 적두(赤豆), 백두(白豆), 녹두(綠豆)를 모두 소두(小豆)라고 하지만 특히 적소두(赤小豆)는 약에 넣는 붉고 작은 것이라 하여 지금의 팥을 의미하고 있으며, 이뇨, 소염, 배농, 해열에 효능이 있으며, 전신부종, 간경화, 황달, 종기, 화농성 질환, 수종, 각기병, 소갈, 이질설사 등에 쓰인다. 약리작용으로 볼거리염, 타박상, 유즙분비촉진 등이 보고되었다.
이에, 본 발명자들은 염증성 부종의 예방 또는 치료 효과를 가지며 부작용이 없는 천연 추출물을 포함하는 조성물을 개발하기 위해 예의 노력한 결과, 적소두 추출물이 염증 및 부종을 억제하는 것을 확인하여, 본 발명을 완성하였다.
본 발명의 목적은 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 개선용 식품 조성물을 제공하는 것이다.
본 발명의 목적은 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 치료용 약학적 조성물을 제공하는 것이다.
본 발명의 목적은 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 개선용 화장료 조성물을 제공하는 것이다.
본 발명의 목적은 약학적으로 유효한 양의 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 치료용 약학적 조성물을 개체에 투여하는 단계를 포함하는 부종의 예방 및 치료방법을 제공하는 것이다.
본 발명의 목적은 유효한 양의 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 개선용 식품 조성물 또는 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 개선용 화장료 조성물을 개체에 투여하는 단계를 포함하는 부종 예방 및 개선방법을 제공하는 것이다.
본 발명은 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 개선용 식품 조성물을 제공한다.
본 발명은 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 치료용 약학적 조성물을 제공 한다.
본 발명은 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 개선용 화장료 조성물을 제공한다.
본 발명은 약학적으로 유효한 양의 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 치료용 약학적 조성물을 개체에 투여하는 단계를 포함하는 부종의 예방 및 치료방법을 제공한다.
본 발명은 유효한 양의 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 개선용 식품 조성물 또는 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 개선용 화장료 조성물을 개체에 투여하는 단계를 포함하는 부종 예방 및 개선방법을 제공한다.
본 발명의 적소두 추출물은 동물모델에 LPS를 투여하여 염증반응을 일으킨 후, 본 발명의 적소두 추출물을 투여하여, 염증 매개 물질 및 염증 반응에서 발현되는 IL-1 beta mRNA, IL-6 mRNA, TNF-alpha, IL-4를 억제시킴을 확인 하였다. 또한, 염증 초기반응에 관여하는 IL-10 발현을 증가 및 후천면역 반응에 관여하는 IL-18을 억제시고, 동물모델의 발바닥의 부종 또한 육안상 감소시켰으며, 발바닥 조직의 침윤세포 감소를 확인하였는 바, 염증성 부종 개선 및 치료에 효과적임을 확인하여, 염증성 부종과 관련된 유용한 사업에 사용될 수 있다.
도 1은 IL-6, IL-1 beta, TNF-alpha, IL-4, IL-10 및 IL-18의 mRNA 서열번호를 나타낸 도이다.
도 2는 LPS를 투여하여 피부 부종이 유도된 마우스모델의 적소두 추출물을 투여하여, 마우스 모델의 발 크기(높이와 가로 합산)를 나타낸 도이다.
도 3은 LPS를 투여하여 피부 부종이 유도된 마우스모델의 적소두 추출물을 투여하여 IL-1 beta의 mRNA 발현을 억제를 나타낸 도이다.
도 4는 LPS를 투여하여 피부 부종이 유도된 마우스모델의 적소두 추출물을 투여하여 IL-6의 mRNA 발현 억제를 나타낸 도이다.
도 5는 LPS를 투여하여 피부 부종이 유도된 마우스모델의 적소두 추출물을 투여하여 TNF-alpha의 mRNA 발현 상승 억제를 나타낸 도이다.
도 6은 LPS를 투여하여 피부 부종이 유도된 마우스모델의 적소두 추출물을 투여하여 IL-4 mRNA 발현량 차단을 나타낸 도이다.
도 7은 LPS를 투여하여 피부 부종이 유도된 마우스모델의 적소두 추출물을 투여하여 IL-10 mRNA의 발현량이 유의적으로 높음을 나타낸 도이다.
도 8은 LPS를 투여하여 피부 부종이 유도된 마우스모델의 적소두 추출물을 투여하여 IL-18 mRNA의 발현 상승 차단을 나타낸 도이다.
도 9는 LPS를 투여하여 피부 부종이 유도된 마우스모델의 적소두 추출물을 투여하여 마우스 모델 발바닥의 부종 억제를 외관상 나타낸 도이다.
도 10은 LPS를 투여하여 피부 부종이 유도된 마우스모델의 적소두 추출물을 투여하여 마우스 모델 발바닥 조직의 침윤세포 감소 효과를 나타낸 도이다.
이하, 첨부된 도면을 참조하여 본 발명의 구현예로 본 발명을 상세히 설명하기로 한다. 다만, 하기 구현예는 본 발명에 대한 예시로 제시되는 것으로, 당업자에게 주지 저명한 기술 또는 구성에 대한 구체적인 설명이 본 발명의 요지를 불필요하게 흐릴 수 있다고 판단되는 경우에는 그 상세한 설명을 생략할 수 있고, 이에 의해 본 발명이 제한되지는 않는다, 본 발명은 후술하는 특허청구범위의 기재 및 그로부터 해석되는 균등 범주 내에서 다양한 변형 및 응용이 가능하다.
또한, 본 명세서에서 사용되는 용어 (terminology)들은 본 발명의 바람직한 실시예를 적절히 표현하기 위해 사용된 용어들로서, 이는 사용자, 운용자의 의도 또는 본 발명이 속하는 분야의 관례 등에 따라 달라질 수 있다. 따라서, 본 용어들에 대한 정의는 본 명세서 전반에 걸친 내용을 토대로 내려져야 할 것이다. 명세서 전체에서, 어떤 부분이 어떤 구성요소를 "포함"한다고 할 때, 이는 특별히 반대되는 기재가 없는 한 다른 구성요소를 제외하는 것이 아니라 다른 구성 요소를 더 포함할 수 있는 것을 의미한다.
본 발명에서 사용되는 모든 기술용어는, 달리 정의되지 않는 이상, 본 발명의 관련 분야에서 통상의 당업자가 일반적으로 이해하는 바와 같은 의미로 사용된다. 또한 본 명세서에는 바람직한 방법이나 사료가 기재되나, 이와 유사하거나 동등한 것들도 본 발명의 범주에 포함된다. 본 명세서에 참고문헌으로 기재되는 모든 간행물의 내용은 본 발명에 도입된다.
본 발명은 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 개선용 식품 조성물을 제공한다.
본 발명의 식품 조성물은 유효성분을 함유하는 것 외에 통상의 식품 조성물과 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다.
상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨,소르비톨, 에리트리톨 등의 당알콜이다. 상술한 향미제는 천연 향미제 (타우마틴), 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제 (사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 본 발명의 식품 조성물은 상기 약학적 조성물과 동일한 방식으로 제제화되어 기능성 식품으로 이용하거나, 각종 식품에 첨가할 수 있다. 본 발명의 조성물을 첨가할 수 있는 식품으로는 예를 들어, 음료류, 육류, 초코렛, 식품류, 과자류, 피자, 라면, 기타 면류, 껌류, 사탕류, 아이스크림류, 알코올 음료류, 비타민 복합제 및 건강보조식품류 등이 있다.
또한 상기 식품 조성물은 유효성분인 추출물 외에 여러 가지 영양제, 비타민, 광물 (전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제 (치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 식품 조성물은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다.
본 발명의 기능성 식품 조성물은, 정제,캅셀, 분말, 과립, 액상, 환 등의 형태로 제조 및 가공될 수 있다. 본 발명에서 '건강기능성 식품 조성물'이라 함은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 말하며, 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다. 본 발명의 건강기능식품은 통상의 식품 첨가물을 포함할 수 있으며, 식품 첨가물로서의 적합 여부는 다른 규정이 없는 한, 식품의약품안전청에 승인된 식품 첨가물 공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다. 상기 '식품 첨가물 공전'에 수재된 품목으로는 예를 들어, 케톤류, 글리신, 구연산칼슘, 니코틴산, 계피산 등의 화학적 합성물; 감색소, 감초추출물, 결정셀룰로오스, 고량색소, 구아검 등의 천연첨가물; L-글루타민산나트륨 제제, 면류첨가알칼리제, 보존료 제제, 타르색소제제 등의 혼합제제류 등을 들 수 있다. 예를 들어, 정제 형태의 건강기능식품은 본 발명의 유효성분을 부형제, 결합제, 붕해제 및 다른 첨가제와 혼합한 혼합물을 통상의 방법으로 과립화한 다음, 활택제 등을 넣어 압축성형하거나, 상기 혼합물을 직접 압축 성형할 수 있다. 또한 상기 정제 형태의 건강기능식품은 필요에 따라 교미제 등을 함유할 수도 있다. 캅셀 형태의 건강기능식품 중 경질 캅셀제는 통상의 경질 캅셀에 본 발명의 유효성분을 부형제 등의 첨가제와 혼합한 혼합물을 충진하여 제조할 수 있으며, 연질 캅셀제는 본 발명의 유효성분을 부형제 등의 첨가제와 혼합한 혼합물을 젤라틴과 같은 캅셀기제에 충진하여 제조할 수 있다. 상기 연질 캅셀제는 필요에 따라 글리세린 또는 소르비톨 등의 가소제, 착색제, 보존제 등을 함유할 수 있다. 환 형태의 건강기능식품은 본 발명의 유효성분과 부형제, 결합제, 붕해제 등을 혼합한 혼합물을 기존에 공지된 방법으로 성형하여 조제할 수 있으며, 필요에 따라 백당이나 다른 제피제로 제피할 수 있으며, 또는 전분, 탈크와 같은 물질로 표면을 코팅할 수도 있다. 과립 형태의 건강기능식품은 본 발명의 유효성분의 부형제, 결합제, 붕해제 등을 혼합한 혼합물을 기존에 공지된 방법으로 입상으로 제조할 수 있으며, 필요에 따라 착향제, 교미제 등을 함유할 수 있다.
프레타놀A는 주정을 원료로 만든 식물성 에탄올로서, 보통 의료 및 식품회사의 살균세척에 많이 사용되며, 천연디퓨저 및 모기퇴치제에 많이 사용된다.
프레타놀A 75%는 식품을 부패시키고 신선도를 저해시키는 각조 세균을 억제하므로 식품 가공시 보존성을 향상시키는 용도로 사용하고, 프레타놀A 95%는 비누나 화장품등 무수 알코올 사용하는 용도로 사용된다.
상기 부종은 염증성 부종, 특발성 부종, 심부전으로 인한 부종, 신장질환으로 인한 부종, 림프, 정맥 등의 혈관계 이상으로 인한 부종 및 외과 및 성형수술로 인한 염증성 부종으로 이루어진 군에서 1종 이상인 것이나, 바람직하게는 외과 및 성형수술로 인한 염증성 부종인 것이다.
상기 적소두 추출물은 물, C1 내지 C4의 저급 알코올 또는 이들의 혼합용매로 이루어진 군에서 선택된 어느 하나의 용매로 추출된 것일 수 있으나, 이에 제한되지 않으나, 바람직하게는 프레타놀A인 것이다.
상기 조성물은 IFN-gamma를 감소시키는 것이나, 이에 제한되지 않는다.
상기 조성물은 IL-1 beta, IL-6, TNF-alpha, IL-4 및 IL-18 발현을 억제시키는 것이나, 이에 제한되지 않는다.
상기 조성물은 IL-10 발현을 증가시키는 것이나, 이에 제한되지 않는다.
상기 조성물은 염증세포의 침윤을 감소 시키는 것이나, 이에 제한되지 않는다.
상기 적소두 추출물은 0~400mg/kg인 것이나, 바람직하게는 100~300mg/kg인 것이다.
본 발명은 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 치료용 약학적 조성물을 제공한다.
본 발명의 약학 조성물에는 유효성분 이외에 보조제(adjuvant)를 추가로 포함할 수 있다. 상기 보조제는 당해 기술분야에 알려진 것이라면 어느 것이나 제한 없이 사용할 수 있으나, 예를 들어 프로인트(Freund)의 완전 보조제 또는 불완전 보조제를 더 포함하여 그 면역성을 증가시킬 수 있다.
본 발명에 따른 약학 조성물은 유효성분을 약학적으로 허용된 담체에 혼입시킨 형태로 제조될 수 있다. 여기서, 약학적으로 허용된 담체는 제약 분야에서 통상 사용되는 담체, 부형제 및 희석제를 포함한다. 본 발명의 약학 조성물에 이용할 수 있는 약학적으로 허용된 담체는 이들로 제한되는 것은 아니지만, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로스, 메틸 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다.
본 발명의 약학 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀전, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 또는 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.
제제화할 경우에는 통상 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 그러한 고형 제제는 유효성분에 적어도 하나 이상의 부형제, 예를 들면 전분, 칼슘 카르보네이트, 수크로스, 락토오스, 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용될 수 있다. 경구투여를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데, 일반적으로 사용되는 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수용성용제, 현탁제, 유제, 동결건조 제제 및 좌제가 포함된다. 비수용성용제, 현탁제로는 프로필렌 글리콜, 폴리에틸렌 글리콜, 올리브유와 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 트윈(tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.
본 발명에 따른 약학 조성물은 개체에 다양한 경로로 투여될 수 있다. 투여의 모든 방식이 예상될 수 있는데, 예를 들면 경구, 정맥, 근육, 피하, 복강내 주사에 의해 투여될 수 있다.
본 발명에 따른 약학 조성물의 투여량은 개체의 연령, 체중, 성별, 신체 상태 등을 고려하여 선택된다. 상기 약학 조성물 중 포함되는 유효성분의 농도는 대상에 따라 다양하게 선택할 수 있음은 자명하며, 바람직하게는 약학 조성물에 0.01 ~ 5,000 ㎍/ml의 농도로 포함되는 것이다. 그 농도가 0.01 ㎍/ml 미만일 경우에는 약학 활성이 나타나지 않을 수 있고, 5,000 ㎍/ml를 초과할 경우에는 인체에 독성을 나타낼 수 있다.
상기 약학 조성물은 다양한 경구 또는 비경구 투여 형태로 제형화될 수 있다.
경구 투여용 제형으로는 예를 들면 정제, 환제, 경질, 연질 캅셀제, 액제, 현탁제, 유화제, 시럽제, 과립제 등이 있는데, 이들 제형은 유효성분 이외에 희석제(예: 락토즈, 덱스트로즈, 수크로즈, 만니톨, 솔비톨, 셀룰로즈 및/또는 글리신), 활택제(예: 실리카, 탈크, 스테아르산 및 그의 마그네슘 또는 칼슘염 및/ 또는 폴리에틸렌 글리콜)를 추가로 포함할 수 있다. 또한, 상기 정제는 마그네슘 알루미늄 실리케이트, 전분 페이스트, 젤라틴, 트라가칸스, 메틸셀룰로즈, 나트륨 카복시메틸셀룰로즈 및/또는 폴리비닐피롤리딘과 같은 결합제를 함유할 수 있으며, 경우에 따라 전분, 한천, 알긴산 또는 그의 나트륨 염과 같은 붕해제 또는 비등 혼합물 및/또는 흡수제, 착색제, 향미제 및 감미제를 함유할 수 있다. 상기 제형은 통상적인 혼합, 과립화 또는 코팅 방법에 의해 제조될 수 있다.
또한, 비경구 투여용 제형의 대표적인 것은 주사용 제제이며, 주사용 제제의 용매로서 물, 링거액, 등장성 생리식염수 또는 현탁액을 들 수 있다. 상기 주사용 제제의 멸균 고정 오일은 용매 또는 현탁 매질로서 사용할 수있으며 모노-, 디-글리세라이드를 포함하여 어떠한 무자극성 고정오일도 이러한 목적으로 사용될 수 있다.
또한, 상기 주사용 제제는 올레산과 같은 지방산을 사용할 수 있다.
본 발명의 조성물은 항생제 내성균 감염성 피부 질환의 예방 또는 개선용 등에 다양하게 이용될 수 있다. 본 조성물을 첨가할 수 있는 제품으로는, 예를 들어, 각종 크림, 로션, 스킨, 에센스 등과 같은 화장품류와 샴푸, 린스, 클렌징, 세안제, 비누, 트리트먼트, 팩, 미용액 등이 있다.
본 발명은 적소두(Phaseolus angularis Wight) 추출물을 유효성분으로 포함하는 부종 예방 및 개선용 화장료 조성물을 제공한다.
본 발명의 화장료는 수용성 비타민, 지용성 비타민, 고분자 펩티드, 고분자 다당, 스핑고 지질 및 해초 추출물로 이루어진 군에서 선택된 조성물을 포함한다.
수용성 비타민으로서는 화장품에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 비타민 B1, 비타민 B2, 비타민 B6, 피리독신, 염산피리독신, 비타민 B12, 판토텐산, 니코틴산, 니코틴산아미드, 엽산, 비타민 C, 비타민 H 등을 들 수 있으며, 그들의 염 (티아민염산염, 아스코르빈산나트륨염 등)이나 유도체 (아스코르빈산-2-인산나트륨염, 아스코르빈산-2-인산마그네슘염 등)도 본 발명에서 사용할 수 있는 수용성 비타민에 포함된다. 수용성 비타민은 미생물 변환법, 미생물의 배양물로부터의 정제법, 효소법 또는 화학 합성법 등의 통상의 방법에 의해 수득할 수 있다.
지용성 비타민으로서는 화장품에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 비타민 A, 카로틴, 비타민 D2, 비타민 D3, 비타민 E (d1-알파 토코페롤, d-알파 토코페롤, d-알파 토코페롤) 등을 들 수 있으며, 그들의 유도체(팔미틴산아스코르빈, 스테아르산아스코르빈, 디팔미틴산아스코르빈, 아세트산dl-알파 토코페롤, 니코틴산dl-알파 토코페롤비타민 E, DL-판토테닐알코올, D-판토테닐알코올, 판토테닐에틸에테르 등) 등도 본 발명에서 사용되는 지용성 비타민에 포함된다. 지용성 비타민은 미생물 변환법, 미생물의 배양물로부터의 정제법, 효소 또는 화학 합성법 등의 통상의 방법에 의해 취득할 수 있다.
고분자 펩티드로서는 화장품에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 콜라겐, 가수 분해 콜라겐, 젤라틴, 엘라스틴, 가수 분해 엘라스틴, 케라틴 등을 들 수 있다. 고분자 펩티드는 미생물의 배양액으로부터의 정제법, 효소법 또는 화학 합성법 등의 통상의 방법에 의해 정제 취득할 수 있으며, 또는 통상 돼지나 소 등의 진피, 누에의 견섬유 등의 천연물로부터 정제하여 사용할 수 있다.
고분자 다당으로서는 화장품에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 히드록시에틸셀룰로오스, 크산탄검, 히알루론산나트륨, 콘드로이틴 황산 또는 그 염 (나트륨염 등) 등을 들 수 있다. 예를 들어, 콘드로이틴 황산 또는 그 염 등은 통상 포유 동물이나 어류로부터 정제하여 사용할 수 있다.
스핑고 지질로서는 화장품에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 세라미드, 피토스핑고신, 스핑고당지질 등을 들 수 있다. 스핑고 지질은 통상 포유류, 어류, 패류, 효모 또는 식물 등으로부터 통상의 방법에 의해 정제하거나 화학 합성법에 의해 취득할 수 있다.
본 발명의 화장료에는 상기 필수 성분과 더불어 필요에 따라 통상 화장료에 배합되는 다른 성분을 배합해도 된다. 이외에 첨가해도 되는 배합 성분으로서는 유지성분, 보습제, 에몰리엔트제, 계면 활성제, 유기 및 무기안료, 유기 분체, 자외선 흡수제, 방부제, 살균제, 산화 방지제, 식물 추출물, pH 조정제, 알콜, 색소, 향료, 혈행 촉진제, 냉감제, 제한(制汗)제, 정제수 등을 들 수 있다. 유지 성분으로서는 에스테르계 유지, 탄화수소계 유지, 실리콘계 유지, 불소계 유지, 동물 유지, 식물 유지 등을 들 수 있다.
에스테르계 유지로서는 트리2-에틸헥산산글리세릴, 2-에틸헥산산세틸, 미리스틴산이소프로필, 미리스틴산 부틸, 팔미틴산이소프로필, 스테아르산에틸, 팔미틴산옥틸, 이소스테아르산이소세틸, 스테아르산부틸, 리놀레산 에틸, 리놀레산이소프로필, 올레인산에틸, 미리스틴산이소세틸, 미리스틴산이소스테아릴, 팔미틴산이소스테아릴, 미리스틴산옥틸도데실, 이소스테아르산이소세틸, 세바신산디에틸, 아디핀산디이소프로필, 네오펜탄산이소알킬, 트리(카프릴, 카프린산)글리세릴, 트리2-에틸헥산산트리메틸롤프로판, 트리이소스테아르산 트리메틸롤프로판, 테트라2-에틸헥산산펜타엘리슬리톨, 카프릴산세틸, 라우린산데실, 라우린산헥실, 미리스틴산데실, 미리스틴산미리스틸, 미리스틴산세틸, 스테아르산스테아릴, 올레인산데실, 리시노올레인산세틸, 라우린산이소스테아릴, 미리스틴산이소트리데실, 팔미틴산이소세틸, 스테아르산옥틸, 스테아르산 이소세틸, 올레인산이소데실, 올레인산옥틸도데실, 리놀레산옥틸도데실, 이소스테아르산이소프로필, 2-에틸헥산산세토스테아릴, 2-에틸헥산산스테아릴, 이소스테아르산헥실, 디옥탄산에틸렌글리콜, 디올레인산에틸렌글리콜, 디카프린산프로필렌글리콜, 디(카프릴, 카프린산)프로필렌글리콜, 디카프릴산프로필렌글리콜, 디카프린산네오펜 틸글리콜, 디옥탄산네오펜틸글리콜, 트리카프릴산글리세릴, 트리운데실산글리세릴, 트리이소팔미틴산글리세릴, 트리이소스테아르산글리세릴, 네오펜탄산옥틸도데실, 옥탄산이소스테아릴, 이소노난산옥틸, 네오데칸산헥실데실, 네오데칸산옥틸도데실, 이소스테아르산이소세틸, 이소스테아르산이소스테아릴, 이소스테아르산옥틸데실, 폴리글리세린올레인산에스테르, 폴리글리세린이소스테아르산에스테르, 시트르산트리이소세틸, 시트르산트리이소알킬, 시트르산트리이소옥틸, 락트산라우릴, 락트산미리스틸, 락트산세틸, 락트산옥틸데실, 시트르산트리에틸, 시트르산아세틸트리에틸, 시트르산아세틸트리부틸, 시트르산트리옥틸, 말산디이소스테아릴, 히드록시스테아르산 2-에틸헥실, 숙신산디2-에틸헥실, 아디핀산디이소부틸, 세바신산디이소프로필, 세바신산디옥틸, 스테아르산콜레스테릴, 이소스테아르산콜레스테릴, 히드록시스테아르산콜레스테릴, 올레인산콜레스테릴, 올레인 산디히드로콜레스테릴, 이소스테아르산피트스테릴, 올레인산피트스테릴, 12-스테알로일히드록시스테아르산이소세틸, 12-스테알로일히드록시스테아르산스테아릴, 12-스테알로일히드록시스테아르산이소스테아릴 등의 에스테르계 등을 들 수 있다.
탄화수소계 유지로서는 스쿠알렌, 유동 파라핀, 알파-올레핀올리고머, 이소파라핀, 세레신, 파라핀, 유동 이소파라핀, 폴리부덴, 마이크로크리스탈린왁스, 와셀린 등의 탄화수소계 유지 등을 들 수 있다.
실리콘계 유지로서는 폴리메틸실리콘, 메틸페닐실리콘, 메틸시클로폴리실록산, 옥타메틸폴리실록산, 데카메틸폴리실록산, 도데카메틸시클로실록산, 디메틸실록산 및 메틸세틸옥시실록산 공중합체, 디메틸실록산 및 메틸스테알록시실록산 공중합체, 알킬 변성 실리콘유, 아미노 변성 실리콘유 등을 들 수 있다.
불소계 유지로서는 퍼플루오로폴리에테르 등을 들 수 있다.
동물 또는 식물 유지로서는 아보카도유, 아르몬드유, 올리브유, 참깨유, 쌀겨유, 새플라워유, 대두유, 옥수수유, 유채유, 행인(杏仁)유, 팜핵유, 팜유, 피마자유, 해바라기유, 포도종자유, 면실유, 야자유, 쿠쿠이너트유, 소맥배아유, 쌀 배아유, 시아버터, 월견초유, 마커데이미아너트유, 메도홈유, 난황유, 우지(牛脂), 마유, 밍크유, 오렌지라피유, 호호바유, 캔데리러왁스, 카르나바왁스, 액상 라놀린, 경화피마자유 등의 동물 또는 식물 유지를 들 수 있다.
보습제로서는 수용성 저분자 보습제, 지용성 분자 보습제, 수용성 고분자, 지용성 고분자 등을 들 수 있다.
수용성 저분자 보습제로서는 세린, 글루타민, 솔비톨, 만니톨, 피롤리돈-카르복실산나트륨, 글리세린, 프로필렌글리콜, 1,3-부틸렌글리콜, 에틸렌글리콜, 폴리에틸렌글리콜B(중합도 n = 2 이상), 폴리프로필렌글리콜(중합도 n = 2 이상), 폴리글리세린B(중합도 n = 2 이상), 락트산, 락트산염 등을 들 수 있다.
지용성 저분자 보습제로서는 콜레스테롤, 콜레스테롤에스테르 등을 들 수 있다.
수용성 고분자로서는 카르복시비닐폴리머, 폴리아스파라긴산염, 트라가칸트, 크산탄검, 메틸셀룰로오스, 히드록시메틸셀룰로오스, 히드록시에틸셀룰로오스, 히드록시프로필셀룰로오스, 카르복시메틸셀룰로오스, 수용성키틴, 키토산, 덱스트린 등을 들 수 있다.
지용성 고분자로서는 폴리비닐피롤리돈 및 에이코센 공중합체, 폴리비닐피롤리돈 및 헥사데센 공중합체, 니트로셀룰로오스, 덱스트린지방산에스테르, 고분자 실리콘 등을 들수 있다. 에몰리엔트제로서는 장쇄아실글루타민산 콜레스테릴에스테르, 히드록시스테아르산콜레스테릴, 12-히드록시스테아르산, 스테아르산, 로진산, 라놀린지방산콜레스테릴에스테르 등을 들 수 있다.
계면 활성제로서는 비이온성 계면 활성제, 음이온성 계면 활성제, 양이온성 계면 활성제, 양성 계면 활성제 등을 들 수 있다.
비이온성 계면 활성제로서는 자기 유화형 모노스테아르산글리세린, 프로필렌글리콜지방산에스테르, 글리세린 지방산에스테르, 폴리글리세린지방산에스테르, 솔비탄지방산에스테르, POE(폴리옥시에틸렌)솔비탄지방산에스테르, POE 솔비트지방산에스테르, POE 글리세린지방산에스테르, POE 알킬에테르, POE 지방산에스테르, POE 경화피마자유, POE 피마자유, POE 및 POP(폴리옥시에틸렌 및 폴리옥시프로필렌) 공중합체, POE 및 POP 알킬에테르, 폴리에테르변성실리콘, 라우린산알카놀아미드, 알킬아민옥시드, 수소첨가 대두인지질 등을 들 수 있다.
음이온성 계면 활성제로서는 지방산비누, 알파-아실술폰산염, 알킬술폰산염, 알킬알릴술폰산염, 알킬나프탈렌술폰산염, 알킬황산염, POE 알킬에테르황산염, 알킬아미드황산염, 알킬인산염, POE 알킬인산업, 알킬아미드 인산염, 알킬로일알킬타우린염, N-아실아미노산염, POE 알킬에테르카르복실산염, 알킬술포숙신산염, 알킬술포아세트산나트륨, 아실화 가수분해 콜라겐펩티드염, 퍼플루오로알킬인산에스테르 등을 들 수 있다.
양이온성 계면 활성제로서는 염화알킬트리메틸암모늄, 염화스테아릴트리메틸암모늄, 브롬화스테아릴트리메틸암모늄, 염화세토스테아릴트리메틸암모늄, 염화디스테아릴디메틸암모늄, 염화스테아릴디메틸벤질암모늄, 브롬화베헤닐트리메틸암모늄, 염화벤잘코늄, 스테아르산 디에틸아미노에틸아미드, 스테아르산디메틸아미노프로필아 미드, 라놀린 유도체 제 4급 암모늄염 등을 들 수 있다.
양성 계면 활성제로서는 카르복시베타인형, 아미드베타인형, 술포베타인형, 히드록시술포베타인형, 아미드 술포 베타인형, 포스포베타인형, 아미노카르복실산염형, 이미다졸린 유도체형, 아미드아민형 등의 양성 계면 활성제 등을 들 수 있다.
유기 및 무기 안료로서는 규산, 무수규산, 규산마그네슘, 탤크, 세리사이트, 마이카, 카올린, 벵갈라, 클레이, 벤토나이트, 티탄피막운모, 옥시염화비스무트, 산화지르코늄, 산화마그네슘, 산화아연, 산화티탄, 산화알루미늄, 황산칼슘, 황산바륨, 황산마그네슘, 탄산칼슘, 탄산마그네슘, 산화철, 군청, 산화크롬, 수산화크롬, 칼라민 및 이들의 복합체등의 무기 안료; 폴리아미드, 폴리에스테르, 폴리프로필렌, 폴리스티렌, 폴리우레탄, 비닐수지, 요소수지, 페놀수지, 불소수지, 규소수지, 아크릴수지, 멜라민수지, 에폭시수지, 폴리카보네이트 수지, 디비닐벤젠 및 스티렌 공중합체, 실크파우더, 셀룰로오스, CI 피그먼트옐로우, CI 피그먼트오렌지 등의 유기 안료 및 이들의 무기 안료와 유기 안료의 복합 안료 등을 들 수 있다.
유기 분체로서는 스테아르산칼슘 등의 금속비누; 세틸린산아연나트륨, 라우릴린산아연, 라우릴린산칼슘 등의 알킬인산금속염; N-라우로일-베타-알라닌칼슘, N-라우로일-베타-알라닌아연, N-라우로일글리신칼슘 등의 아실아미노산 다가금속염; N-라우로일-타우린칼슘, N-팔미토일-타우린칼슘 등의 아미드술폰산 다가금속염; N-엡실론-라우로일-L-리진, N-엡실론-팔미토일리진, N-알파-파리토일올니틴, N-알파-라우로일아르기닌, N-알파-경화우지지방산아실아르기닌 등의 N-아실염기성아미노산; N-라우로일글리실글리신 등의 N-아실폴리펩티드; 알파-아미노카프릴산, 알파-아미노라우린산 등의 알파-아미노지방산; 폴리에틸렌, 폴리프로필렌, 나일론, 폴리메틸메타크릴레이트, 폴리스티렌, 디비닐벤젠 및 스티렌 공중합체, 사불화에틸렌 등을 들 수 있다.
자외선 흡수제로서는 파라아미노벤조산, 파라아미노벤조산에틸, 파라아미노벤조산아밀, 파라아미노벤조산옥틸, 살리실산에틸렌글리콜, 살리신산페닐, 살리신산옥틸, 살리신산벤질, 살리신산부틸페닐,살리신산호모멘틸, 계피산벤질, 파라메톡시계피산-2-에톡시에틸, 파라메톡시계피산옥틸, 디파라메톡시계피산모 노-2-에틸헥산글리세릴, 파라메톡시 계피산 이소프로필, 디이소프로필 및 디이소프로필계피산에스테르 혼합물, 우로카닌산, 우로카닌산에틸, 히드록시메톡시벤조페논, 히드록시메톡시벤조페논술폰산 및 그 염, 디히드록시메톡시벤조페논, 디히드록시메톡시벤조페논디술폰산나트륨, 디히드록시벤조페논, 테트라히드록시벤조페논, 4-tert-부틸-4'-메톡시디벤조일메탄, 2,4,6-트리아닐리노-p-(카르보-2'-에틸헥실-1'-옥시)-1,3,5-트리아진, 2-(2-히드록시-5-메틸페닐)벤조트리아졸 등을 들 수 있다.
살균제로서는 히노키티올, 트리클로산, 트리클로로히드록시디페닐에테르, 크로르헥시딘글루콘산염, 페녹시에탄올, 레조르신, 이소프로필메틸페놀, 아줄렌, 살리칠산, 진크필리티온, 염화벤잘코늄, 감광소 301 호, 모노니트로과이어콜나트륨, 운데시렌산 등을 들 수 있다.
산화 방지제로서는 부틸히드록시아니솔, 갈릭산프로필, 엘리소르빈산 등을 들 수 있다.
pH 조정제로서는 시트르산, 시트르산나트륨, 말산, 말산나트륨, 프말산, 프말산나트륨, 숙신산, 숙신산나트륨, 수산화나트륨, 인산일수소나트륨 등을 들 수 있다.
알코올로서는 세틸알코올 등의 고급 알코올을 들 수 있다.
또한, 이외에 첨가해도 되는 배합 성분은 이에 한정되는 것은 아니며, 또, 상기 어느 성분도 본 발명의 목적 및 효과를 손상시키지 않는 범위 내에서 배합 가능하다.
본 발명의 화장료는 용액, 유화물, 점성형 혼합물 등의 형상을 취할 수 있다.
본 발명의 화장료 조성물에 포함되는 성분은 유효성분으로서 화장료 조성물에 통상적으로 이용되는 성분들을 포함할 수 있으며, 예를 들면, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제 및 담체를 포함한다.
본 발명의 화장료 조성물은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어 유액, 크림, 화장수, 팩, 파운데이션, 로션, 미용액, 모발화장료 등을 들 수 있다.
구체적으로, 본 발명의 화장료 조성물은 스킨로션, 스킨소프너, 스킨토너, 밀크 로션, 아스트린젠트, 로션, 모이스쳐 로션, 영양로션, 맛사지크림, 영양크림, 모이스처크림, 핸드크림, 파운데이션, 에센스, 영양에센스, 팩, 비누, 클렌징폼, 클렌징로션, 클렌징크림, 헤어로션, 헤어토닉, 헤어에센스, 헤어샴푸, 헤어린스, 헤어트리트먼트, 바디로션 및 바디클린저의 제형을 포함한다.
본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물섬유, 식물섬유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화 아연 등이 이용될 수 있다.
본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.
본 발명의 제형이 용액 또는 유탁액의 경우에는 담체 성분으로서 용매, 용매화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.
본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.
본 발명의 제형이 계면활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산디에탄올아미드, 식물성유, 리놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.
본 발명은 약학적으로 유효한 양의 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 치료용 약학적 조성물을 개체에 투여하는 단계를 포함하는 부종의 예방 및 치료방법을 제공한다.
또한 본 발명은 약학적으로 유효한 양의 상기 적소두 추출물을 유효성분으로 포함하는 부종 예방 및 치료용 약학적 조성물을 개체에 투여하는 단계를 포함하는 부종 예방 및 치료방법을 제공한다. 본 발명의 약학 조성물은 치료적 유효량 또는 약학으로 유효한 양으로 투여한다. 용어 "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다.
이하 하기 실시예를 통해 본 발명을 보다 상세히 설명한다. 그러나 하기 실시예는 본 발명의 기술적 사상의 내용과 범위를 쉽게 설명하기 위한 예시일 뿐, 이에 의해 본 발명의 기술적 범위가 한정되거나 변경되는 것은 아니다. 또한 이러한 예시에 기초하여 본 발명의 기술적 사상의 범위 안에서 다양한 변형과 변경이 가능함은 당업자에 의해 용이하게 결정될 수 있다.
[준비예]
준비예 1.
부종과 관련된 염증 매개물질 및 관련인자의 mRNA분석.
NucleoZOL을 이용하여 정상 마우스 동물 모델의 발바닥 조직의 mRNA를 분리한 뒤, cDNA를 합성하고 아래에 도 1에 표시된 특정 Primer와 반응시켜 IL-6, IL-1 beta, TNF-alpha, IL-4, IL-10 및 IL-18 mRNA 서열을 조사하였다(도 1).
[실시예]
실시예 1. 적소두 추출물의 제조
본 실험의 적소두는 광명당 한약도매상에서 구입하여 실험을 진행하였다. 적소두를 500g을 부직포에 넣고 10배(5 L)의 프레타놀A 25%를 채우고 환류추출기(MS-609, Korea)를 이용하여 80℃에서 3시간 2회 추출 후 대형 회전감압농축기(Eyela, CA-2600-chiller가 장착된 Eyela, NVC-2200, Japan)를 이용하였고 55℃에서 30 hPa 농축하여 10 brix 내외의 표준 추출물을 제작하였다. 추출물을 Deep freezer(Themo Scientific, TSE600D, U.S.A)를 이용하여 -70℃에서 동결하였고 동결건조기(일신, 본디로 LYOPH-PRIDE 20R)로 옮긴 후 동결 건조를 실시하였다. 124시간 후 종료된 동결건조기로부터 추출물을 53 g(10.6%) 수득하였다.
실시예 2. 적소두 추출물의 부종 억제 효과를 발 크기 외관상으로 확인.
본 발명의 적소두 추출물을 100, 200 및 300 mg/kg의 농도로 일주일간 경구투여한 뒤, 성형수술과 시술로 인한 부종 및 염증 모델을 제작하기 위하여, 200 ng/paw LPS를 투여하여 피부 부종이 유도된 마우스모델에 부종을 개선할 수 있는지 마우스모델의 발바닥을 외관상 확인하였다.
부종 형성은 염증세포의 침윤과 염증성 물질의 축적으로 나타나게 되고, LPS는 피부 염증반응에서 피부 조직의 부종을 일으키는 것으로 알려져 있다. 따라서, LPS를 투여한 피부 부종이 유도된 마우스모델에 음성대조군(Negative control, 0.84 ± 0.04 cm), 정상대조군(Normal control, 0.64 ± 0.04 cm), 양성대조군(Positive control, 0.64 ± 0.04 cm), 적소두 추출물은 각각 100 (0.765 ± 0.04 cm), 200 (0.735 ± 0.03 cm), 및 300 (0.660 ± 0.04 cm) mg/kg을 투여 하였다.
그 결과, 모든 실험동물의 발 크기(높이와 가로 합산)는 음성대조군은 정상대조군에 비해 발 크기가 유의적으로 증가하였고 양성대조군은 억제 하였으며, 본 발명의 적소두 추출물 또한 음성대조군에 비해 농도의존적으로 부종 개선효능이 나타난 것을 확인하였다(도 2).
실시예 3. 적소두 추출물의 부종의 초기반응인 IFN-gamma의 감소 효과 확인
본 발명의 적소두 추출물을 100, 200 및 300 mg/kg의 농도로 일주일간 경구투여한 뒤, 성형수술과 시술로 인한 부종 및 염증 모델을 제작하기 위하여, 200 ng/paw LPS를 투여하여 피부 부종이 유도된 마우스모델에 IFN-gamma 감소 시킬수 있는지 확인하였다.
IFN-gamma는 항바이러스 작용을 가지고, 염증 반응에 관여하는 주요 인자로 직접적으로 대식세포를 활성화 시키거나 세포독성 T 세포의 분화를 촉진시키며, 또한, LPS는 IFN-gamma 발현을 증가시키고 염증반응에 의한 조직의 부종 형성 초기에 관여할 뿐만 아니라 피부의 긴사슬지방산과 세라마이드를 감소시켜 피부 보호 기능을 떨어트린다.
따라서, LPS를 투여한 피부 부종이 유도된 마우스모델에 음성대조군(Negative control, 39.9 ± 5.2 pg/mL), 정상대조군(Normal control, 19.8 ± 3.7 pg/mL), 양성대조군(Positive control, 22.3 ± 1.9 pg/mL), 적소두 추출물 각각 100 mg/kg (64.6 ± 5.0). 적소두 추출물 200 mg/kg (37.9 ± 4.3), 적소두 추출물 300 mg/kg (34.0 ± 5.0)를 투여하여, 동물모델에 혈청을 분석하였다.
그 결과, 적소두 추출물의 용량부터 IFN-gamma가 유의적으로 감소효과가 확인되었다. 따라서, 본 발명의 적소두 추출물은 부종 형성의 초기 반응에 관여할 가능성이 있는 것을 확인 하였다.
실시예 4. 적소두 추출물의 IL-1 beta 발현 억제 효과 확인.
본 발명의 적소두 추출물을 100, 200 및 300 mg/kg의 농도로 일주일간 경구투여한 뒤, 성형수술과 시술로 인한 부종 및 염증 모델을 제작하기 위하여, 200 ng/paw LPS를 투여하여 피부 부종이 유도된 마우스모델에 IL-1 beta의 mRNA 발현 억제 할 수 있는지 확인 하였다.
IL-1 beta는 직접적으로 피부 세포의 염증 매개물질 분비를 유도해 염증 반응을 증가시켜 피부자극을 유발하고, 유발된 염증반응을 통해 건선과 아토피 피부염 같은 피부질환을 유발하는 인자로써 피부 염증 개선 효능 평가에 흔히 사용되는 인자이다.
따라서, LPS를 투여한 피부 부종이 유도된 마우스모델에 음성대조군(Negative control), 정상대조군(Normal control), 양성대조군(Positive control), 적소두 추출물 각각 100 mg/kg, 적소두 추출물 200 mg/kg, 적소두 추출물 300 mg/kg를 투여하였다.
그 결과, 본 발명의 적소두 추출물이 IL-1 beta의 mRNA 발현량에 억제를 농도 의존적으로 억제하는 것을 확인하였다(도 3).
실시예 5. 적소두 추출물의 IL-6 발현 억제 효과 확인.
본 발명의 적소두 추출물을 100, 200 및 300 mg/kg의 농도로 일주일간 경구투여한 뒤, 성형수술과 시술로 인한 부종 및 염증 모델을 제작하기 위하여, 200 ng/paw LPS를 투여하여 피부 부종이 유도된 마우스모델에 IL-6 beta의 mRNA 발현 억제 할 수 있는지 확인 하였다.
IL-6는 피부 염증과 피부 재생에 모두 관여한다고 알려져 있으며, 피부에 일어난 염증 초기 단계에서 염증인자인 IL-1과 TNF-alpha에 의해 유도되며 피부의 표피세포, 내피세표, 간질세포 및 대식세포로부터 전염증성 인자의 방출을 촉진시킨다. 또한, 과한 염증 상태에서 IL-6는 matrix metalloproteinase(MMP)의 발현을 촉진하고 피부 기질을 분해시킬 뿐만 아니라 염증 자극에 대해 반응성이 높으며, 다른 염증인자와 비교해 발현 속도가 빠르기 때문에 염증 반응에 있어 중요한 인자로 취급된다.
따라서, LPS를 투여한 피부 부종이 유도된 마우스모델에 음성대조군(Negative control), 정상대조군(Normal control), 양성대조군(Positive control), 적소두 추출물 각각 100 mg/kg, 적소두 추출물 200 mg/kg, 적소두 추출물 300 mg/kg를 투여하였다.
그 결과, 본 발명의 적소두 추출물은 200mg/kg 부터 IL-6 beta의 mRNA 발현이 억제 되어, IL-6 beta의 mRNA 발현 억제하는 것을 확인하였다(도 4).
실시예 6. 적소두 추출물의 TNF-alpha
발현 억제 효과 확인.
본 발명의 적소두 추출물을 100, 200 및 300 mg/kg의 농도로 일주일간 경구투여한 뒤, 성형수술과 시술로 인한 부종 및 염증 모델을 제작하기 위하여, 200 ng/paw LPS를 투여하여 피부 부종이 유도된 마우스모델에 TNF-alpha의 mRNA 발현 억제 할 수 있는지 확인 하였다.
TNF-alpha는 ultraviolet B(UVB), LPS 또는 피부 자극에 의한 피부 염증 반응에서 발현량이 증가한다. 또한, 염증 활성을 발달시켜 피부의 내피부착인자 발현량을 초래하고 림프구의 침윤과 T-림프구의 순환에 관여할 뿐만 아니라 염증 부위에 백혈구를 응집시킨다.
따라서, LPS를 투여한 피부 부종이 유도된 마우스모델에 음성대조군(Negative control), 정상대조군(Normal control), 양성대조군(Positive control), 적소두 추출물 각각 100 mg/kg, 적소두 추출물 200 mg/kg, 적소두 추출물 300 mg/kg를 투여하였다.
그 결과, 본 발명의 적소두 추출물은 200mg/kg 부터 TNF-alpha의 mRNA 발현이 억제 되어, TNF-alpha의 mRNA 발현 억제를 농도 의존적으로 억제하는 것을 확인하였다(도 5).
실시예 7. 적소두 추출물의 IL-4 발현 억제 효과 확인.
본 발명의 적소두 추출물을 100, 200 및 300 mg/kg의 농도로 일주일간 경구투여한 뒤, 성형수술과 시술로 인한 부종 및 염증 모델을 제작하기 위하여, 200 ng/paw LPS를 투여하여 피부 부종이 유도된 마우스모델에 IL-4의 mRNA 발현 억제 할 수 있는지 확인 하였다.
IL-4는 피부 자극에 의한 피부 염증반응에서 표피 분화 복합체(epidermal differentiation complex)에 관련된 유전자를 조절하여 피부의 회복과 보호 기능을 감소시키는 작용을 매개하는 것으로 알려져 있다.
따라서, LPS를 투여한 피부 부종이 유도된 마우스모델에 음성대조군(Negative control), 정상대조군(Normal control), 양성대조군(Positive control), 적소두 추출물 각각 100 mg/kg, 적소두 추출물 200 mg/kg, 적소두 추출물 300 mg/kg를 투여하였다.
그 결과, 본 발명의 적소두 추출물은 농도 의존적으로 IL-4 mRNA 발현을 억제 시키는것을 확인 하였다(도 6).
실시예 8. 적소두 추출물의 IL-10 발현 효과 확인.
본 발명의 적소두 추출물을 100, 200 및 300 mg/kg의 농도로 일주일간 경구투여한 뒤, 성형수술과 시술로 인한 부종 및 염증 모델을 제작하기 위하여, 200 ng/paw LPS를 투여하여 피부 부종이 유도된 마우스모델에 IL-10의 mRNA 발현 억제 할 수 있는지 확인 하였다.
IL-10은 항염증 사이토카인으로 여러 백혈구에 의해 생산되며 특히 조절 T세포는 IL-10의 분비를 통해 면역억제기능을 가지며, 피부의 내피에서 외부 항원에 대한 과도한 면역반응을 억제한다. LPS에 의해 발현이 증가된 IL-10은 초기 염증반응에서 염증성 쇼크를 조절하거나 산화질소(nitric oxide)와 같은 염증 매개분자의 생성과 작용에 직접적으로 대항한다고 알려져 있다.
따라서, 적소두 추출물을 미리 경구투여한 그룹들은 IL-10 mRNA의 발현량이 대조군과 비교하여 유의적으로 낮았다.
이에 따라, 본 발명의 적소두 추출물은 염증반응 초기에 작용하는 것을 확인 하였다(도 7).
실시예 9. 적소두 추출물의 IL-18 발현 억제 효과 확인.
본 발명의 적소두 추출물을 100, 200 및 300 mg/kg의 농도로 일주일간 경구투여한 뒤, 성형수술과 시술로 인한 부종 및 염증 모델을 제작하기 위하여, 200 ng/paw LPS를 투여하여 피부 부종이 유도된 마우스모델에 IL-18의 mRNA 발현 억제 할 수 있는지 확인 하였다.
IL-18는 IFN-gamma의 생산을 유도하는 전염증성 사이토카인으로 염증조절복합체 활성에 관여하며, 염증반응에서 피부 각질세포의 TNF-alpha 방출을 유도하여 세포자멸사를 초래하는 것으로 알려져 있다. 또한, 활성화된 염증조절복합체는 NF-kB 신호전달 경로를 활성화 하여 염증반을 유발한다.
따라서, LPS를 투여한 피부 부종이 유도된 마우스모델에 음성대조군(Negative control), 정상대조군(Positive control), 적소두 추출물 각각 100 mg/kg, 적소두 추출물 200 mg/kg, 적소두 추출물 300 mg/kg를 투여하였다.
그 결과, 본 발명의 적소두 추출물이 IL-18의 mRNA 발현량에 억제를 농도 의존적으로 억제하는 것을 확인하였다(도 8).
실시예 10. 적소두 추출물의 부종 형성의 억제 외관 및 조직의 침윤세포 확인.
본 발명의 적소두 추출물을 100, 200 및 300 mg/kg의 농도로 일주일간 경구투여한 뒤, 성형수술과 시술로 인한 부종 및 염증 모델을 제작하기 위하여, 200 ng/paw LPS를 투여하여 피부 부종이 유도된 마우스모델의 발 바닥을 외관상 확인하였고, 발 바닥 세포의 침윤세포를 확인 하였다.
LPS는 피부 염증반응에서 피부 조직의 부종을 일으키는 것으로 알려져 있다.
따라서, LPS를 투여한 피부 부종이 유도된 마우스모델에 음성대조군(Negative control), 정상대조군(Positive control), 적소두 추출물 각각 100 mg/kg, 적소두 추출물 200 mg/kg, 적소두 추출물 300 mg/kg를 투여하였다.
그 결과, 음성대조군(Negative control)은 정상대조군과 비교하여 발의 붓기가 증가되었고, 양성대조군 처리군에서 감소되는 것으로 확인하였다(도 9). 또한, 음성대조군(Negative control)은 정상대조군과 비교하여 조직의 염증세포 침윤이 증가되었고, 양성대조군 처리군에서 감소되는 것으로 확인하였다(도 10).
이에 따라, LPS로 피부 부종이 유도된 마우스 모델에서 본 발명의 적소두 추출물이 농도 의존적으로 외관상 부종이 억제된 것을 확인하였고(도 9), 또한 농도 의존적으로 염증세포의 침윤이 감소되는 것을 확인하였다(도 10).
따라서, 본 발명의 적소두 추출물은 붓기 및 염증세포 감소하는 것을 확인 하였다.
이제까지 본 발명에 대하여 그 바람직한 실시예들을 중심으로 살펴보았다. 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할 수 있을 것이다. 그러므로 개시된 실시예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특허청구범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.
Claims (13)
- 적소두(Phaseolus angularis Wight) 추출물을 유효성분으로 포함하는 부종 예방 및 개선용 식품 조성물.
- 제 1항에 있어서,상기 부종은 염증성 부종, 특발성 부종, 심부전으로 인한 부종, 신장질환으로 인한 부종, 림프, 정맥 등의 혈관계 이상으로 외과 및 성형수술로 인한 염증성 부종으로 이루어진 군에서 1종 이상인 것인, 식품 조성물.
- 제 1항에 있어서,상기 적소두 추출물은 물, C1 내지 C4의 저급 알코올 또는 이들의 혼합용매로 이루어진 군에서 선택된 어느 하나의 용매로 추출된 것인, 식품 조성물.
- 제 3항에 있어서,상기 추출 용매는 식물성 에탄올인 프레타놀A인 것인, 식품 조성물.
- 제 1항에 있어서,상기 조성물은 IFN-gamma를 감소시키는 것인, 식품 조성물.
- 제 1항에 있어서,상기 조성물은 IL-1 beta, IL-6, TNF-alpha, IL-4 및 IL-18 발현을 억제시키는 것인, 식품 조성물
- 제 1항에 있어서,상기 조성물은 IL-10 발현을 증가시키는 것인, 식품 조성물
- 제 1항에 있어서,상기 조성물은 염증세포의 침윤을 감소시키는 것인, 식품 조성물.
- 제 1항에 있어서,상기 적소두 추출물은 0~400mg/kg인 것인, 식품 조성물.
- 적소두(Phaseolus angularis Wight) 추출물을 유효성분으로 포함하는 부종 예방 및 치료용 약학적 조성물.
- 적소두(Phaseolus angularis Wight) 추출물을 유효성분으로 포함하는 부종 예방 및 개선용 화장료 조성물.
- 약학적으로 유효한 양의 제10항의 약학적 조성물을 개체에 투여하는 단계를 포함하는 부종 예방 및 치료방법.
- 유효한 양의 제1항의 식품 조성물 또는 제11항의 화장료 조성물을 개체에 투여하는 단계를 포함하는 부종 예방 및 개선방법.
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