WO2020204479A1 - Composition pour soulager des troubles de la circulation veineuse comprenant un extrait de feuille de raisin et un extrait de centella asiatica - Google Patents

Composition pour soulager des troubles de la circulation veineuse comprenant un extrait de feuille de raisin et un extrait de centella asiatica Download PDF

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WO2020204479A1
WO2020204479A1 PCT/KR2020/004180 KR2020004180W WO2020204479A1 WO 2020204479 A1 WO2020204479 A1 WO 2020204479A1 KR 2020004180 W KR2020004180 W KR 2020004180W WO 2020204479 A1 WO2020204479 A1 WO 2020204479A1
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extract
centella asiatica
grape leaf
composition according
leaf extract
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PCT/KR2020/004180
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English (en)
Korean (ko)
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신은주
심규석
김민정
박상준
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주식회사 유니베라
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Publication of WO2020204479A1 publication Critical patent/WO2020204479A1/fr

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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
    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • 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)
    • A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • 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
    • A23V2200/3262—Foods, ingredients or supplements having a functional effect on health having an effect on blood cholesterol
    • 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 relates to a health functional food composition for improving venous circulation disorders, a food composition, a pharmaceutical composition and a cosmetic composition comprising grape leaf extract and centella asiatica extract as active ingredients.
  • Veins are divided into superficial veins, which are shallow veins located very close to the skin, and deep veins, which are deep veins located between or below the muscles under the skin.
  • the veins connecting the shallow and deep veins are called penetrating veins.
  • Varicose veins is a type of venous circulation disorder, and if not treated early, symptoms worsen and the skin turns black, and it can progress to increased venous pressure, inflammation, valve insufficiency (defect), microvascular hyperpermeability, and skin ulcers.
  • various venous circulation disorders occur, and when venous circulation is not smooth, the legs become swollen or numb, and symptoms appear.
  • venous circulatory disorder persists, blood circulation to the heart is not smooth, making systemic blood circulation difficult. Pain, heaviness, swelling, night muscle spasms, itching, etc. may appear in the lower extremities. If left untreated, the blood vessels in the legs appear uneven. It may cause ulcers. These venous circulation disorders can be treated through surgery, but the possibility of recurrence is high due to the absence of a fundamental treatment, so it is important to prevent and manage venous circulation disorders.
  • Korean Patent Laid-Open Publication No. 10-2018-0076262 discloses a fermentation method of black currant having an effect of strengthening capillaries and antioxidant, and improving blood circulation of a composition containing grape seed extract in Korean Patent No. 10-1469801 Although the effects and antioxidant effects of grape seed extract have been disclosed, studies on natural products that can effectively improve venous circulation disorders have not been conducted yet.
  • a natural product-derived composition effective in preventing inflammation and improving swelling that may occur in vein valves and vein walls by combining grape leaves having antioxidant, anti-inflammatory and edema inhibiting effects and centella asiatica having wound healing and anti-inflammatory effects was intended to provide.
  • centella asiatica extract and grape leaf extract were selected as a candidate for a functional raw material capable of managing venous circulation disorders, and to prove the synergistic pharmacological efficacy of the complex for improving venous circulation.
  • the first aspect of the present invention can provide a health functional food composition for preventing or improving venous circulation disorders, comprising grape leaf extract and centella asiatica extract as active ingredients.
  • a second aspect of the present invention can provide a food composition for preventing or improving venous circulation disorders, comprising grape leaf extract and centella asiatica extract as active ingredients.
  • a third aspect of the present invention can provide a pharmaceutical composition for preventing or treating venous circulation disorders, comprising grape leaf extract and centella asiatica extract as active ingredients.
  • a fourth aspect of the present invention can provide a cosmetic composition for preventing or improving venous circulation disorders, comprising grape leaf extract and centella asiatica extract as active ingredients.
  • centella asiatica extract and grape leaf extract of the present invention does not exhibit cytotoxicity even at high concentrations, so it is safe for the living body, and exhibits a synergistic effect on the inhibition of oxidative damage and inflammatory factors of vascular endothelial cells that cause venous circulation disorders. Therefore, it is possible to effectively prevent, improve and treat venous circulation disorders such as varicose veins.
  • 1 is a graph showing by measuring the antioxidant power of centella extract and grape leaf extract complex according to an embodiment of the present invention.
  • ROS active oxygen
  • FIG 3 is a graph showing the effect of releasing nitrogen monoxide (NO) in vascular cells of a centella asiatica extract and grape leaf extract complex according to an embodiment of the present invention.
  • NO nitrogen monoxide
  • FIG. 4 is a graph showing the effect of restoring electrical resistance of a cell monolayer in blood vessel cells of a centella asiatica extract and grape leaf extract complex according to an embodiment of the present invention.
  • FIG. 5 is a graph showing the effect of inhibiting cell permeability in vascular cells induced oxidative stress of centella asiatica extract and grape leaf extract complex according to an embodiment of the present invention.
  • FIG. 6 is a graph showing the effect of inhibiting cell permeability in vascular cells induced an inflammatory response of centella asiatica extract and grape leaf extract complex according to an embodiment of the present invention.
  • FIG. 7 is a graph showing the results of measuring cytotoxicity by concentration of centella asiatica extract and grape leaf extract complex according to an embodiment of the present invention.
  • 9 is a result of a mouse intraperitoneal vascular permeability test measured after oral administration of 400 mg per kg of mouse body weight by varying the mixing ratio of centella asiatica extract and grape leaf extract complex according to an embodiment of the present invention.
  • FIG. 10 is a result of an intraperitoneal vascular permeability experiment in mice in which the mixing ratio and oral dose of centella extract and grape leaf extract complex were varied according to an embodiment of the present invention.
  • FIG. 11 is a photograph of a result of a mouse bivein vascular permeability animal experiment using a centella asiatica extract and grape leaf extract complex according to an embodiment of the present invention, and a graph quantifying it.
  • FIG. 12 is a photograph of the results of an animal test of carrageenan-induced mouse paw edema using a centella asiatica extract and grape leaf extract complex according to an embodiment of the present invention.
  • FIG. 13 is a graph showing the measurement of the thickness of the foot edema according to the animal test of carrageenan-induced mouse foot edema using a centella asiatica extract and grape leaf extract complex according to an embodiment of the present invention.
  • FIG. 14 is a graph showing the measurement of the volume of paw edema according to an animal test of carrageenan-induced mouse paw edema using a centella asiatica extract and grape leaf extract complex according to an embodiment of the present invention.
  • FIG. 15 is a photograph of foot pad edema according to an animal test of carrageenan-induced mouse foot edema in which oral doses of centella extract and grape leaf extract complex according to an embodiment of the present invention are varied.
  • 16 is a side photograph of the sole of the foot according to an animal test of carrageenan-induced mouse foot edema in which oral doses of centella extract and grape leaf extract complex according to an embodiment of the present invention are varied.
  • FIG. 17 is a graph showing the measurement of the volume of paw edema according to an animal experiment in carrageenan-induced mouse paw edema in which oral doses of centella extract and grape leaf extract complex were varied according to an embodiment of the present invention.
  • the term "combination of these" included in the expression of the Makushi form means one or more mixtures or combinations selected from the group consisting of the constituent elements described in the expression of the Makushi form, and the constituent elements It means to include one or more selected from the group consisting of.
  • prevention refers to any action that inhibits or delays the onset by administration of the composition
  • treatment or “improvement” refers to symptomatic improvement or beneficial change by administration of the composition. It means all actions.
  • a first aspect of the present invention can provide a health functional food composition for preventing or improving venous circulation disorders, comprising grape leaf extract and centella asiatica extract as active ingredients.
  • Grape leaf extract and centella asiatica extract contained in the health functional food composition of the present invention reduce oxidative stress, vascular permeability and inflammatory response of vascular cells, inhibit NO production, and reduce edema in vivo, thereby impairing venous circulation Can prevent and/or improve.
  • the health functional food composition of the present invention may exhibit a synergistic effect compared to the case of using the grape leaf extract alone or centella asiatica extract of the same dose by including the grape leaf extract and centella asiatica extract together.
  • the composition of the present invention may contain a grape leaf extract and centella asiatica extract in a weight ratio of 5:1 to 5:1, specifically 3:1 to 1:3, more specifically 2:1 to 3:1 It may be contained in a weight ratio, but may not be limited thereto.
  • the composition may contain a grape leaf extract and centella asiatica extract in a weight ratio of 1:1, 2:1, 3:1, 4:1 or 5:1, specifically 2:1, 2.5: It may be contained in a weight ratio of 1 or 3:1, but may not be limited thereto.
  • the composition contains the grape leaf extract and centella asiatica extract in a weight ratio of 2:1 to 3:1, the effect of preventing and/or improving venous circulation disorders may be particularly excellent.
  • the composition of the present invention may be for ingestion in a dose of 1 mg to 100 mg per kg of body weight of the subject, but may not be limited thereto. Specifically, the composition may be for ingestion at a dose of 2 mg to 50 mg, 3 mg to 30 mg, 4 mg to 20 mg, or 5 mg to 10 mg per kg of the subject's body weight, but may not be limited thereto. .
  • the venous circulation disorder may be varicose veins, specifically varicose veins, or venous insufficiency, but may not be limited thereto, and any disorder or disease caused by poor venous circulation is limited. Without it can be prevented and / or improved by the health functional food composition of the present invention.
  • composition of the present invention can prevent and/or ameliorate one or more symptoms selected from symptoms associated with venous circulation disorders, such as lower extremity pain, swelling, nocturnal muscle spasms, itching, heaviness in the lower extremities, increased venous pressure, and valve failure.
  • symptoms associated with venous circulation disorders such as lower extremity pain, swelling, nocturnal muscle spasms, itching, heaviness in the lower extremities, increased venous pressure, and valve failure.
  • symptoms associated with venous circulation disorders such as lower extremity pain, swelling, nocturnal muscle spasms, itching, heaviness in the lower extremities, increased venous pressure, and valve failure.
  • symptoms associated with venous circulation disorders such as lower extremity pain, swelling, nocturnal muscle spasms, itching, heaviness in the lower extremities, increased venous pressure, and valve failure.
  • symptoms associated with venous circulation disorders such as lower extremity pain, swelling, nocturnal muscle spasms,
  • Grape leaf extract and centella asiatica included in the composition of the present invention may be, for example, pulverized grape leaves, extracted using an extraction solvent, filtered and concentrated, and dried to form a powder, but is limited thereto. May not be.
  • the extraction solvent may be selected from water, an alcohol having 1 to 5 carbon atoms, and a combination thereof, for example, methanol, ethanol, propanol, butanol, pentanol, a mixture of the alcohol and water, or hot water. May not be limited.
  • Foods that may contain the grape leaf extract and centella asiatica extract of the present invention as an active ingredient for example, various foods, powders, granules, tablets, capsules, syrup, beverages, gum, tea, vitamin complex, health functional foods And the like, but may not be limited thereto, and may also be added to food or beverage.
  • the composition of the present invention may be a formulation selected from the group consisting of tablets, pills, powders, granules, powders, capsules, and liquids, but may not be limited thereto.
  • the total amount of the grape leaf extract and centella asiatica extract in food or beverage may be added in an amount of about 0.01 to 15% by weight of the total food weight, and the health beverage composition may be added in an amount of about 0.01 to 10g based on 100 ml. However, it may not be limited thereto.
  • the food composition of the present invention is a beverage composition
  • various flavoring agents or natural carbohydrates, etc. as an ordinary beverage, may be contained as an additional ingredient.
  • the above-described natural carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents tacmatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.)
  • synthetic flavoring agents sacharin, aspartame, etc.
  • the ratio of the natural carbohydrate may generally be in the range of about 1 to 20 g per 100 ml of the composition of the present invention, but may not be limited thereto.
  • composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and heavy weight agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonates used in carbonated beverages, etc. may be included, but may not be limited thereto.
  • composition of the present invention may contain natural fruit juice and flesh for the production of fruit juice beverages and vegetable beverages, and these components may be used independently or in combination.
  • the ratio of these additives is not important, but may be selected from about 0.1 to about 20 parts by weight per 100 parts by weight of the composition of the present invention, but may not be limited thereto.
  • a second aspect of the present invention can provide a food composition for preventing or improving venous circulation disorders, comprising grape leaf extract and centella asiatica extract as active ingredients.
  • the food composition may be a formulation selected from the group consisting of beverages, bread, fats and oils, ice cream, confectionery, gum, rice cakes, snacks, alcoholic beverages, seasonings, and retort foods, including general food forms, but may not be limited thereto. have.
  • a third aspect of the present invention can provide a pharmaceutical composition for preventing or treating venous circulation disorders, comprising grape leaf extract and centella asiatica extract as active ingredients.
  • Grape leaf extract and centella asiatica extract contained in the pharmaceutical composition of the present invention reduce the oxidative stress, vascular permeability and inflammatory response of vascular cells, inhibit NO production, and reduce edema in vivo, thereby reducing venous circulation disorders. It can be prevented and/or treated.
  • the pharmaceutical composition of the present invention may exhibit a synergistic effect compared to the case of using the grape leaf extract alone or Centella asiatica extract of the same dose by including the grape leaf extract and centella asiatica extract together.
  • the pharmaceutical composition may further include a pharmaceutically acceptable carrier and/or diluent.
  • carrier may be defined as a compound that facilitates the addition of the target active ingredient into cells or tissues, and is a commonly used carrier that facilitates the introduction of many organic compounds into cells or tissues of an organism. It can be selected and used without limitation.
  • “diluent” may be defined as a compound that is diluted in a solvent that will dissolve the active ingredient as well as stabilize the biologically active form of the target active ingredient.
  • the salt dissolved in the buffer solution is used as a diluent in the art, and the buffer solution commonly used is a phosphate buffered saline solution that mimics the salt state of a human solution, but may not be limited thereto. Because the buffer salt controls the pH of the solution at low concentrations, the buffer diluent may not modify the biological activity of the compound.
  • the pharmaceutical composition of the present invention is formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods.
  • oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods.
  • Carriers, excipients, and diluents that can be included in the composition containing natural extracts, such as the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, Alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. , May not be limited thereto. In the case of formulation, it can be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the extract, such as starch, calcium carbonate, sucrose ) Or lactose (lactose), gelatin, etc. can be prepared by mixing.
  • excipients in the extract such as starch, calcium carbonate, sucrose ) Or lactose (lactose), gelatin, etc.
  • lubricants such as magnesium stearate and talc may also be used.
  • Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, etc.
  • various excipients such as wetting agents, sweetening agents, fragrances, and preservatives may be included. .
  • Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories.
  • non-aqueous solvent and suspension propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used.
  • injectable ester such as ethyl oleate
  • a base for suppositories witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogelatin, and the like can be used.
  • the preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and weight of the patient, the degree of disease, the drug form, the route and duration of administration, but may be appropriately selected by a person skilled in the art.
  • the pharmaceutical composition of the present invention may be administered in a dose of 1 mg to 100 mg per kg of body weight of the subject, but may not be limited thereto.
  • the pharmaceutical composition may be for administration in a dose of 2 mg to 50 mg, 3 mg to 30 mg, 4 mg to 20 mg, or 5 mg to 10 mg per kg of body weight of the subject, but is not limited thereto.
  • the dosage may be a daily dosage.
  • Administration may be administered once a day, or may be divided several times.
  • the above dosage does not in any way limit the scope of the present invention.
  • the pharmaceutical composition of the present invention can be administered to mammals such as mice, mice, livestock, and humans by various routes. All modes of administration can be expected and can be administered, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dura mater or by intracerebroventricular injection.
  • a fourth aspect of the present invention may provide a cosmetic composition for preventing or improving venous circulation disorders, comprising grape leaf extract and centella asiatica extract as active ingredients.
  • the cosmetic composition of the present invention includes, for example, skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, essence, nutrition essence, pack , Soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, emulsion, lipstick, makeup base, foundation, press powder, and loose powder, but limited thereto. May not be.
  • ingredients included in the cosmetic composition of the present invention may include ingredients commonly used in cosmetic compositions in addition to grape leaf extract and centella as an active ingredient, such as antioxidants, stabilizers, solubilizers, vitamins, pigments and fragrances. It may include a conventional adjuvant, such as, and a carrier.
  • the cosmetic composition of the present invention may be prepared in any formulation conventionally prepared in the art, for example, solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing , Oil, powder foundation, emulsion foundation, wax foundation, and spray, etc., but are not limited thereto, and in addition, flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing It can be made of foam, cleansing water, pack, spray or powder.
  • the formulation of the cosmetic composition is a paste, cream, or gel, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide are used as carrier components.
  • animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide are used as carrier components. Can be.
  • a solvent, a solubilizing agent or an emulsifying agent may be used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene Glycol, 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan can be used.
  • the formulation of the cosmetic composition 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, Crystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, and the like
  • lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component.
  • additional chlorofluorohydrocarbon propane / May contain propellants such as butane or dimethyl ether.
  • propellants such as butane or dimethyl ether.
  • the formulation of the cosmetic composition is a surfactant containing cleansing, as a carrier component, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide ether Sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, or ethoxylated glycerol fatty acid esters may be used.
  • centella, grape leaves, and their complex extracts which are candidate materials for improving venous circulation, using vascular cells.
  • centella asiatica extract For the preparation of centella asiatica extract, centella asiatica leaves were pulverized with a grinder and then extracted using alcohol (Daehan Alcohol Life Co., Ltd., Korea) to the raw material. The extract was filtered under reduced pressure with a paper filter (ADVANTEC 2, 280 mm, China), and the filtrate was concentrated with a rotary vacuum concentrator (Rotavapor® R-220SE, BUCHI, switzerland), and then in a vacuum dryer (Daeil engineering, Korea). After drying, an extract in powder form was obtained.
  • alcohol Daehan Alcohol Life Co., Ltd., Korea
  • grape leaves were pulverized with a grinder, and then extracted using 40% alcohol (Daehan Alcohol Life Co., Ltd., Korea) in the raw material.
  • the extract was filtered under reduced pressure with a paper filter (ADVANTEC 2, 280 mm, China), and the filtrate was concentrated with a rotary vacuum concentrator (Rotavapor® R-220SE, BUCHI, switzerland), and then in a vacuum dryer (Daeil engineering, Korea). After drying, an extract in powder form was obtained.
  • the grape leaf extract and centella asiatica extract prepared by the above method were mixed at a specific mixing ratio and used in the experiment.
  • HUVEC cells were aliquoted into a 96-well plate at 3 ⁇ 10 4 cells/well and cultured for 24 hours. After removing the medium, it was washed once with an assay buffer, and treated with 2', 7'-dichlorofluorcein (DCFDA) 25 ⁇ M, and reacted in an incubator at 37° C. for 45 minutes. After the reaction, the sample was pretreated for 30 minutes after washing once with an analysis buffer. H 2 O 2 500 ⁇ M was treated and reacted for 1 hour and then measured at ex/em 485/530 nm.
  • DCFDA 2', 7'-dichlorofluorcein
  • HUVEC cells were aliquoted into a 96-well plate at 3 ⁇ 10 4 cells/well and cultured for 24 hours. After removing the medium, the sample was pretreated for 30 minutes, and reacted with 500 ⁇ M of H 2 O 2 for 4 hours. After sampling the culture medium, total NO was measured with a NO assay kit (R&D systems).
  • HUVEC cells were dispensed into 12-well transwells at 4 ⁇ 10 5 cells/well and cultured for 24 hours. After removal of the medium, the sample was pretreated for 30 minutes and reacted with 500 ⁇ M of H 2 O 2 for 4 hours. Thereafter, the cell monolayer gap was measured using a Millicell ERS (Millipore) machine.
  • Millicell ERS Millicell ERS
  • HUVEC cells were aliquoted into 24-well transwells at 2 ⁇ 10 5 cells/well and cultured for 24 hours. After removal of the medium, the sample was pretreated for 30 minutes, and reacted with 500 ⁇ M of H 2 O 2 for 4 hours or TNF- ⁇ 50 ng/ml for 6 hours. After 20 minutes reaction by treatment with FITC-Dextran working solution, 100 ⁇ l of the medium in the insert well was sampled. Subsequently, fluorescence was measured at ex/em 485/530 nm.
  • ROS Reactive oxygen
  • Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) in vascular endothelial cells is an active substance that plays a key role in maintaining the homeostasis of endothelial cells such as vascular relaxation and permeability.
  • NO produced by vascular endothelial cells in addition to vascular relaxation, interferes with the expression of inflammatory cytokines, chemokines, and adhesion molecules, thereby blocking recruitment of leukocytes into blood vessels, proliferation of vascular smooth muscle, and platelet aggregation It plays a positive role in regulating the function of vascular endothelial cells by inhibiting the production of tissue factors involved in thrombus formation.
  • the cells were treated with H 2 O 2 to induce oxidative stress, and then the NO release action of the candidate material was measured.
  • the concentration of NO was decreased compared to the control, but it was confirmed that the concentration-dependently decreased NO was recovered when treated with the grape plant complex (FIG. 3 ).
  • the cells were treated with H 2 O 2 to induce oxidative stress, and then the TEER value was measured.
  • H 2 O 2 treatment the TEER value was decreased due to the weakening of the cell monolayer, but it was observed that the TEER value was recovered in a concentration-dependent manner when the vinegar plant was treated (FIG. 4 ).
  • the cells were treated with H 2 O 2 to induce oxidative stress, and then a permeability test was performed.
  • H 2 O 2 oxidative stress
  • a permeability test was performed.
  • the vinegar plant complex was tested for each concentration, it showed the effect of inhibiting the increased cell permeability by H 2 O 2 in a concentration-dependent manner (FIG. 5).
  • the efficacy of the combination of grape leaf extract and centella asiatica extract with a mixing ratio of 3:1 was evaluated at the in vitro level.
  • the Grape Centella asiatica complex showed superior antioxidant capacity than the individual extracts of Grape and Centella asiatica.
  • HUVEC cells which are human venous endothelial cells
  • the grape vinegar complex showed an increase in NO production in cells, and in the TEER measurement and permeability analysis to confirm the inhibitory effect of cell membrane permeability, the vinegar plant complex significantly increased cell membrane permeability due to oxidative stress and inflammation. It was confirmed to suppress. Accordingly, it is analyzed that the vascular permeability inhibitory effect of the candidate material identified through animal experiments is mediated by the inhibition of inflammation induction and vascular protection by the antioxidant action of the Grapevine.
  • vascular permeability In order to test the vascular permeability pharmacological efficacy of the test substances, grape leaf extract, centella asiatica extract, and their complexes, anti-inflammatory efficacy was tested in Raw264.7 cells stimulated with lipopolysaccharide (LPS). In ICR mice, vascular permeability and A paw edema test was conducted. In the mouse animal test, the vascular permeability was tested after oral administration of the test substance for 4 to 7 days, and the vascular permeability test of all animal tests was conducted on the last day 1 hour after administration of the test substance.
  • LPS lipopolysaccharide
  • the environmental conditions of this test are: temperature 23 ⁇ 3°C, relative humidity 50 ⁇ 10%, ventilation frequency 10 to 20 times/hour, lighting time 12 hours (08:00 lit up to 20:00 off) and illuminance 150 to 300 lux. It was carried out in the established laboratory. This test was conducted in compliance with all regulations applicable to the management and use of experimental animals.
  • Animals were kept in individual ventilated stainless steel mesh cages (200W ⁇ 320L ⁇ 145H mm) for acclimatization, administration, and observation periods, with no more than 4 animals per cage.
  • An individual identification card with the test number and animal number was attached to the breeding box.
  • test substance After weighing the test substance, the test substance was suspended and prepared using sterile distilled water at a concentration of 200-600 mg/kg. The test substance was orally administered to the test animal after aspirating the test substance with a feeding needle and a syringe for oral administration to the animal.
  • a mixture of zoletil and lumpen (3:1) was diluted 10 times and injected at 0.3 cc per mouse, anesthetized during the vascular permeability and foot edema test, and then cervical spine dislocation was performed at the end of the test.
  • Raw264.7 cells were dispensed into 96 wells with 1 ⁇ 10 4 cells per well, and after 24 hours, various concentrations of Centella asiatica extract, grape leaf extract, and grape Centella asiatica complex (0 ⁇ 400 ⁇ g/ml) were added and treated for 24 hours.
  • Centella asiatica extract, grape leaf extract, and grape Centella asiatica complex were evaluated to have no cytotoxicity at concentrations of 400 ⁇ g or less per ml, the highest concentration in this test.
  • Raw264.7 cell line was pretreated with the extract of grapefruit for 1 to 4 hours, and then LPS (0.5 ⁇ g/ml) was reacted for 24 hours, and the expression of inflammatory targets was evaluated. As a result, it was found that the expression of IL-1 ⁇ , IL-6, iNOS and COX-2 was inhibited in a concentration-dependent manner (FIG. 8).
  • Sencia or Anti-Starx as a positive control material was administered at 400 mg per kg for 1 week, and as a test substance, Grape Centella complex (1:3), Grape Centella The complex (1: 1) and grape vinegar complex (3: 1) were orally administered at 400 mg per kg (Table 3).
  • 0.1 cc of 2% Evans blue was administered causally, stabilized for 15 minutes, and then 0.1 cc of 0.78% acetic acid per body weight was injected into the abdominal cavity, and 10 ml of physiological saline was added into the abdominal cavity after 20 minutes. After retrieval, the OD value was measured at 620 nm to test intraperitoneal hemopermeability.
  • vascular permeability was inhibited in all groups administered with the vinegar plant complex compared to the trigger group with increased vascular permeability, and also showed a tendency to be inhibited in a concentration-dependent manner (FIG. 10).
  • the 400 mg administration group with a ratio of 3:1 ratio of the grape plantain plant exhibits excellent vascular permeability inhibitory effect compared to the administration group with a 2:1 ratio (FIG. 10).
  • mice Five-week-old ICR mice were purified in an animal room for one week, and then each test substance was orally administered for 4 days. The test substance was orally administered 1 hour before the last day of administration. After that, 50 ⁇ l of 1% carrageenan was administered intradermally to the sole of the foot, and at 1, 3, or 5 hours, the thickness and volume of the sole of the foot were swelled using a digital caliper and a digital plethysmometer (LE-7500). Was measured.
  • a digital caliper and a digital plethysmometer LE-7500
  • mice were administered with a normal control group, an induction control group, dexamethasone, and a variety of mixed ratios of grape vinegar complex at 400 mg per kg body weight (Table 6).
  • Dexamethasone was used as a positive control by administering 2 mg per kg of body weight. The test results were evaluated through a photograph of the foot edema, the thickness of the foot, and the volume of the foot.
  • the test results were evaluated through a photograph of the foot edema, the thickness of the foot, and the volume of the foot.
  • swelling and redness were the least observed in the Grape Centella asiatica complex administration groups (300 mg and 600 mg) (Fig. 15), and the edema was the most in the Grape Centella asiatica complex administration groups (300 mg and 600 mg) on the plantar lateral picture. It was observed to be weak ( Figure 16).
  • the volume of foot edema decreased in the groups administered with the vinegar plant complex in terms of the volume change of foot edema (Fig. 17).
  • centella asiatica and grape leaf extracts have been reported to have vascular protection.
  • asiatic acid known as an active ingredient of Centella asiatica (L.) Urban, is known to have wound healing, neuroprotection, and blood lipid reduction effects, and is known to have efficacy in several clinical studies on atherosclerosis.
  • the total triterpenic fraction of is reported to inhibit the formation of atherosclerotic plaques when administered in combination with pycnogenol, an active ingredient of pine bark extract.
  • pycnogenol an active ingredient of pine bark extract.
  • the total triterphenyl fraction of Centella asiatica has improved capillary permeation pressure and alleviating symptoms of microcirculatory disorders in hypertensive patients.
  • asiatic acid is known to have anti-inflammatory, anti-angiogenic, anti-oxidative, plasma glucose reduction and metabolic effects.
  • Grape leaf extract is known to be effective for mucous membrane protection, defecation relief, antipyretic action, gastrointestinal protection, anti-diuretic, chronic bronchitis, gout and heart disease, but not as much research as grape fruit and grape seed.
  • the grape vinegar complexes did not show cytotoxicity up to 400 ⁇ g/ml concentration in Raw264.7 cells, it was evaluated that there was no cytotoxicity even at very high concentrations.
  • inflammatory cytokines which are factors affecting vascular permeability
  • TNF- ⁇ , IL-1 ⁇ , and IL-6 which were mainly increased by LPS, were found in the pretreatment of Grapevine complex. It has been shown to be strongly inhibited by.
  • the expression of these inflammatory targets was strongly suppressed in the test to evaluate the mRNA and protein expression levels of the inflammatory targets iNOS and COX-2. Therefore, it was analyzed that the vinegar plant complex has an inhibitory effect on vascular permeability by inhibiting inflammatory cytokines and inflammatory target proteins.
  • the vinegar plant complex was evaluated to inhibit the vascular permeability caused by acetic acid, mustard oil and carrageenan increased intraperitoneal, intravenous, and foot edema, respectively. These complexes were evaluated to exhibit particularly excellent efficacy at a concentration of 300 mg or more per kg body weight, and were evaluated to have efficacy in both 2:1 and 3:1 in the mixing ratio.
  • Increased vascular permeability in the intraperitoneal cavity by intraperitoneal administration of acetic acid is due to direct damage to vascular endothelial cells by acetic acid, and it was analyzed that the vinegar plant complex reduces vascular permeability by protecting such vascular endothelial cell damage.
  • the change in vascular permeability of the bivein due to mustard oil is also directly stimulated by the blood vessels, thereby increasing vascular permeability.
  • the vascular permeability was reduced by the vasoprotective action of the vinegar plant complex.
  • the carrageenan-induced mouse paw edema test it was also confirmed that the increased paw edema due to inflammation was reduced by the anti-inflammatory and vasoprotective effects of the vinegar plant complex.

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Abstract

La présente invention concerne une composition alimentaire fonctionnelle de santé, une composition alimentaire, une composition pharmaceutique et une composition cosmétique, pour soulager des troubles de la circulation veineuse, comprenant chacun un extrait de feuille de raisin et un extrait de Centella asiatica en tant que principes actifs.
PCT/KR2020/004180 2019-03-29 2020-03-27 Composition pour soulager des troubles de la circulation veineuse comprenant un extrait de feuille de raisin et un extrait de centella asiatica WO2020204479A1 (fr)

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KR1020190036896A KR20200115927A (ko) 2019-03-29 2019-03-29 포도잎 추출물 및 병풀 추출물을 포함하는 정맥순환 장애 개선용 조성물
KR10-2019-0036896 2019-03-29

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JP2006516542A (ja) * 2002-12-31 2006-07-06 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 血液循環の改善方法
KR20060101456A (ko) * 2003-09-19 2006-09-25 인데나 에스피아 셀룰라이트의 치료를 위한 경구용 조성물
KR20060130149A (ko) * 2003-12-29 2006-12-18 베링거 인겔하임 인터내셔날 게엠베하 적색 포도나무 잎의 수성 추출물 및 혈액 순환 개선제를포함하는, 만성 정맥 부전증을 치료하기 위한 조성물
KR20140142765A (ko) * 2013-06-04 2014-12-15 한경수 포도 잎 추출물을 유효성분으로 함유하는 혈전 질환의 예방 또는 개선용 식품 조성물 및 약학 조성물

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KR20060101456A (ko) * 2003-09-19 2006-09-25 인데나 에스피아 셀룰라이트의 치료를 위한 경구용 조성물
KR20060130149A (ko) * 2003-12-29 2006-12-18 베링거 인겔하임 인터내셔날 게엠베하 적색 포도나무 잎의 수성 추출물 및 혈액 순환 개선제를포함하는, 만성 정맥 부전증을 치료하기 위한 조성물
KR20140142765A (ko) * 2013-06-04 2014-12-15 한경수 포도 잎 추출물을 유효성분으로 함유하는 혈전 질환의 예방 또는 개선용 식품 조성물 및 약학 조성물

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