WO2021034080A1 - Composition pour la prévention ou le traitement d'une maladie allergique ou de la dermatite atopique comprenant de la carvone ou un sel associé comme principe actif - Google Patents

Composition pour la prévention ou le traitement d'une maladie allergique ou de la dermatite atopique comprenant de la carvone ou un sel associé comme principe actif Download PDF

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WO2021034080A1
WO2021034080A1 PCT/KR2020/010976 KR2020010976W WO2021034080A1 WO 2021034080 A1 WO2021034080 A1 WO 2021034080A1 KR 2020010976 W KR2020010976 W KR 2020010976W WO 2021034080 A1 WO2021034080 A1 WO 2021034080A1
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composition
atopic dermatitis
active ingredient
weight
prevention
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PCT/KR2020/010976
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English (en)
Korean (ko)
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박태선
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연세대학교 산학협력단
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • 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
    • 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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35—Ketones, e.g. benzophenone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q13/00—Formulations or additives for perfume preparations
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/005—Preparations for sensitive 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
    • A23V2200/304—Foods, ingredients or supplements having a functional effect on health having a modulation effect on allergy and risk of allergy
    • 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
    • A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
    • 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
    • A23V2250/30—Other Organic compounds

Definitions

  • the present invention relates to a composition for the prevention or treatment of allergic diseases or atopic dermatitis, comprising carbon (Carvone) or a salt thereof as an active ingredient.
  • Atopy is derived from the ancient Greek word'atopia', which means'strange, abnormal'.
  • Cooke and Coca first began to refer to a tendency that could genetically trigger a specific immune antibody response to an allergen, called atopy. With a steadily increasing trend worldwide, the incidence rate is increasing in developed countries with industrial development.
  • atopy The cause of the onset of atopy has not been accurately identified yet, but is not limited to one factor such as family history, changes in diet, penetration of allergens, and abnormal skin barriers. It occurs mainly in infancy and infancy, and may persist or begin in adulthood. Typical symptoms of atopy appear on the hands, scalp, face, neck, and elbows, but there are differences in the patterns that appear by period. Symptoms of infancy are rough skin and dryness, dermatitis on the outside of limbs, cheeks and foreheads, and sores or scabs sit after scratching with hands. In childhood, it mainly appears on the folds of arms, legs and neck rather than the face, and the skin becomes dry. In puberty and adulthood, symptoms of thickening of the skin on areas such as the face and hands appear.
  • Topical steroids are used when atopic symptoms are severe and are the most basic method to manage bacterial or viral infections.
  • steroids have been introduced in 1950 and have been used for many years, but long-term use is restricted due to problems of skin safety and tolerance depending on the frequency, concentration, and duration of use.
  • potential skin side effects such as skin, atrophy, telangiectasia, and steroid acne, as well as inhibition of hypohalamic-pituitary-adrenal (HPA), and Cushing's syndrome. Sufficient care should be taken when using it as it may cause side effects.
  • HPA hypohalamic-pituitary-adrenal
  • the local immunomodulators tacrolimus and pimecrolimus are known to be used over a long period of time for the purpose of preventing recurrence of lesions as they have a relatively low possibility of side effects even when used for a long time, unlike conventional topical steroids. It is suitable for use as a treatment and maintenance therapy. However, tacrolimus may have side effects such as decreased kidney function, hand tremor, and hair loss, and pimecrolimus may have serious side effects such as acne and burning as well as skin cancer and lymphoma. When steroids worsen in the acute phase, local immunomodulators are suitable for use as treatment and maintenance therapy for mild atopy, but safety against side effects has not yet been secured, so there is an urgent need for alternative supplements.
  • the applicant of the present invention has made efforts to develop a material that has few side effects and is effective in relieving atopic dermatitis symptoms, and as a result, confirming that Carvone relieves atopic symptoms and improves the inflammatory response. Completed.
  • Another object of the present invention is to provide a composition for the prevention or improvement of allergic diseases or atopic dermatitis comprising carbon or a salt thereof as an active ingredient.
  • the present invention is to solve the above-described problems, and provides a pharmaceutical composition for the prevention or treatment of allergic diseases or atopic dermatitis, comprising as an active ingredient carboxylic (Carvone) or a pharmaceutically acceptable salt thereof.
  • carboxylic Carvone
  • the allergic disease is edema, anaphylaxis, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, contact It may be selected from the group consisting of sexual dermatitis, urticaria, pruritus, insect allergy, food allergy and drug allergy, but is not limited thereto.
  • the active ingredient expresses IL-4 (Interleukin-4), IL-13, TNF- ⁇ (tumor necrosis factor-alpha), IL-1 ⁇ , IL-6, or IL-8.
  • IL-4 Interleukin-4
  • IL-13 TNF- ⁇ (tumor necrosis factor-alpha)
  • TNF- ⁇ tumor necrosis factor-alpha
  • IL-1 ⁇ IL-6
  • IL-8 IL-8
  • the present invention provides a quasi-drug composition for the prevention or improvement of allergic diseases or atopic dermatitis comprising carbon or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention provides a cosmetic composition for the prevention or improvement of allergic diseases or atopic dermatitis comprising carbon or a cosmetically acceptable salt thereof as an active ingredient.
  • the present invention provides a perfume composition for the prevention or improvement of allergic diseases or atopic dermatitis, comprising carbon or a cosmetically acceptable salt thereof as an active ingredient.
  • the present invention provides a health functional food composition for the prevention or improvement of allergic diseases or atopic dermatitis, comprising as an active ingredient carbonyl or a food acceptable salt thereof.
  • the present invention provides a method for preventing or treating allergic diseases or atopic dermatitis, comprising administering or taking a composition comprising carbon or a pharmaceutically acceptable salt thereof as an active ingredient to an individual.
  • the present invention provides a use of a composition comprising carbon or a pharmaceutically acceptable salt thereof as an active ingredient to prevent or treat allergic diseases or atopic dermatitis.
  • composition comprising the carboxylic acid of the present invention as an active ingredient has an effect of improving atopic dermatitis due to an allergic reaction, and can be used as a composition for preventing or treating (improving) various allergic diseases by reducing the inflammatory response.
  • FIG. 1 is a graph showing the change in the secretion amount of histamine in mast cells (RBL-2H3 cells) treated with Carvone (each value is the mean ⁇ SEM of three times obtained from three independent wells; on a bar) Letters show a statistically significant difference at P ⁇ 0.05).
  • IL-4, IL-13 and TNF- ⁇ inflammatory cytokine-related molecules
  • Carvone each value is obtained from three independent wells. Mean ⁇ SEM of one trip; the letters on the bars represent statistically significant differences at P ⁇ 0.05).
  • 3 is a graph showing changes in the expression of inflammatory cytokine-related molecules (IL-1 ⁇ , IL-6 and IL-8) in keratinocytes treated with Carvone (each value is from 3 independent wells. Means of 3 obtained ⁇ SEM; letters on the bars show statistically significant differences at P ⁇ 0.05).
  • the present inventors found that carbon relieves atopic symptoms and expresses IL-4, IL-13, TNF- ⁇ , IL-1 ⁇ , IL-6, or IL-8, which are inflammatory cytokines secreted due to the immune response of cells. By confirming that the amount of secretion of histamine was significantly reduced and the amount of histamine was decreased, the present invention was completed.
  • the present invention provides a composition for preventing or treating (improving) allergic diseases or atopic dermatitis, comprising carbon (Carvone) or a salt thereof as an active ingredient.
  • the carvone is a terpenoid-based compound, and the IUPAC name is 2-methyl-5-(prop-1-en-2-yl)cyclohex-2-ene- 1-one (2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-one).
  • the chemical formula of carbon is C 10 H 14 O, the molecular weight is 150.2 g/mol, and the structure is as shown in [Chemical Formula 1] (molecular structure of carvone). Carbon is a colorless or pale yellow transparent liquid and is soluble in water, alcohol, chloroform ether, etc., but not in glycerol.
  • Carbon is known to be a safe edible substance, and has been approved as a flavor agent by EFSA (European Food Safety Athority) and JECFA (Joint FAO/WHO Expert Committee on Food Additives), and industrially has taste and aroma. It has been used for betting purposes.
  • EFSA European Food Safety Athority
  • JECFA Joint FAO/WHO Expert Committee on Food Additives
  • the carbon of the present invention may include a carboxylic hydrate, a carboxylic derivative, and the like within a range having the same efficacy as the carbon, and may also include a solvate or stereoisomer thereof.
  • the method for obtaining the carbon is not particularly limited, and may be isolated from a plant containing the carbon, chemically synthesized using a known manufacturing method, or a commercially available one may be used.
  • the carbon may be d-carvone (d-Carvone, Formula 2 below).
  • the term “cosmetically acceptable salt”, “food pharmaceutically acceptable salt”, “pharmaceutically acceptable salt” or “salt thereof” may be an acid addition salt formed by a free acid.
  • the acid addition salt can be prepared by a conventional method, for example, dissolving the compound in an excess aqueous acid solution, and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile.
  • a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile.
  • the same molar amount of the compound and an acid or alcohol (eg, glycol monomethyl ether) in water may be heated, and then the mixture may be evaporated to dryness, or the precipitated salt may be suction filtered.
  • an inorganic acid or an organic acid may be used as the free acid.
  • the inorganic acid may be hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, and the like, which may be used alone or in combination of two or more.
  • the organic acid include methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid (propionic acid).
  • the carbon can be made cosmetically or food acceptable metal salt using a base.
  • the alkali metal or alkaline earth metal salt can be obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and evaporating and drying the filtrate.
  • the metal salt it is particularly preferable to prepare a sodium, potassium or calcium salt, but is not limited thereto.
  • the corresponding silver salt can be obtained by reacting an alkali metal or alkaline earth metal salt with an appropriate silver salt (eg, silver nitrate).
  • the salt of the carboxylic may include all salts of acidic or basic groups that may be present in the compound of the carboxylic.
  • the salt of the carboxylic acid may include sodium, calcium and potassium salts of the hydroxy group, and other cosmetically acceptable salts of the amino group include hard bromide, sulfuric acid, hydrogen sulfate, phosphate, hydrogen phosphate , Dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, and the like, and salts known in the art It can be manufactured through a manufacturing method.
  • allergic disease refers to a disease caused by an allergy reaction in which the body's immune response to an external antigen is excessive, and specifically, edema, hypersensitivity (anaphylaxis), allergic rhinitis (allergic) rhinitis), asthma, allergic conjunctivitis, allergic dermatitis, contact dermatitis, urticaria, pruritus, insect allergy, food allergy, and drug allergy.
  • edema hypersensitivity (anaphylaxis)
  • allergic rhinitis Allergic rhinitis
  • asthma allergic conjunctivitis
  • allergic dermatitis allergic dermatitis
  • contact dermatitis contact dermatitis
  • urticaria pruritus
  • pruritus insect allergy
  • food allergy food allergy
  • atopic dermatitis is one of allergic diseases and is a skin disease accompanied by symptoms such as itching, dry skin, increased skin thickness, and characteristic eczema.
  • the pharmaceutical composition for the prevention or treatment of allergic diseases or atopic dermatitis is not particularly limited in its content as long as it contains carbonyl or a pharmaceutically acceptable salt thereof, but preferably the dose of carboxylic is 0.1 It may be included in a concentration of ⁇ M to 1000 ⁇ M, but is not limited thereto. At this time, if the carbon is less than the above concentration range, there is a problem that it is difficult to exert a desirable preventive or therapeutic effect, and if the carbon exceeds the above concentration range, there may be concerns of toxicity including cytotoxicity.
  • the pharmaceutical composition for the prevention or treatment of allergic diseases or atopic dermatitis according to a conventional method, respectively, oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and It may be formulated and used in the form of a sterile injectable solution, and may include a suitable carrier, excipient, or diluent commonly used in the preparation of pharmaceutical compositions for formulation.
  • lactose As the carrier or excipient or diluent, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, undecided And various compounds or mixtures including vaginal cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
  • formulation it can be prepared using diluents or excipients such as fillers, weight agents, binders, wetting agents, disintegrants, and surfactants that are usually used.
  • diluents or excipients such as fillers, weight agents, binders, wetting agents, disintegrants, and surfactants that are usually used.
  • Solid preparations for oral administration may be prepared by mixing the carbon with at least one excipient, such as starch, calcium bonate, sucrose or lactose, gelatin, and the like.
  • excipients such as starch, calcium bonate, sucrose or lactose, gelatin, and the like.
  • lubricants such as magnesium stearate and talc can also be used.
  • Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, etc.
  • various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. may be included. .
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous agents, suspensions, emulsions, lyophilized formulations, 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, glycerol gelatin, and the like can be used.
  • the preferred dosage of the pharmaceutical composition for the prevention or treatment of allergic diseases or atopic dermatitis varies depending on the patient's condition, weight, degree of disease, drug form, route and duration of administration, but may be appropriately selected by those skilled in the art. I can. However, for a desirable effect, it may be administered at 0.0001 to 2,000 mg/kg per day, preferably 0.001 to 2,000 mg/kg. Administration may be administered once a day, or may be divided several times. However, the scope of the present invention is not limited by the dosage.
  • the pharmaceutical composition for the prevention or treatment of allergic diseases or atopic dermatitis can be administered to mammals such as mice, mice, livestock, and humans by various routes. All modes of administration can be administered by, for example, oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
  • composition comprising the active ingredient according to the present invention reduces the expression of IL-4, IL-13, TNF- ⁇ , IL-1 ⁇ , IL-6, or IL-8 that is excessively secreted due to an immune response, or By reducing the amount of secretion, allergic diseases or atopic dermatitis symptoms can be improved and prevented.
  • Histamine a representative itching mediator, was proposed by Lewis in 1927 to cause itching in inflammatory skin diseases.
  • the main source of histamine in the skin is mast cells, and histamine, which is synthesized and stored, is secreted in response to stimulation.
  • the secreted histamine causes erythema, pain, vasodilation and swelling due to direct action on blood vessels and release of neuropeptide from sensory nerves in addition to itching through histamine receptors present in keratinocytes.
  • the inflammatory cytokines IL-4, IL-13, TNF- ⁇ , IL-1 ⁇ , IL-6 and IL-8 secreted by the immune response of cells
  • the inflammatory cytokines IL-4, IL-13, TNF- ⁇ , IL-1 ⁇ , IL-6 and IL-8 secreted by the immune response of cells
  • the present invention provides a composition for preventing or improving allergic diseases or atopic dermatitis, including carvone or a salt thereof as an active ingredient.
  • the specific content of the carbon is as described above.
  • the composition for preventing or improving allergic diseases or atopic dermatitis of the present invention may be a health functional food composition, a cosmetic composition, a perfume composition, or a quasi-drug composition.
  • the term "health functional food” refers to a food manufactured and processed in the form of tablets, capsules, powders, granules, liquids and pills using raw materials or ingredients having useful functions for the human body.
  • “functionality” means obtaining useful effects for health purposes such as controlling nutrients or physiological effects on the structure and function of the human body.
  • the health functional food of the present invention can be prepared by a method commonly used in the art, and at the time of manufacture, it can be prepared by adding raw materials and ingredients commonly added in the art.
  • the formulation of the health functional food may be prepared without limitation as long as it is a formulation recognized as a health functional food.
  • the health functional food composition of the present invention has the advantage of not having side effects that may occur when taking the drug for a long period of time, unlike general drugs, using food as a raw material, and is excellent in portability, enhancing the anti-allergic effect or the relief effect of atopic dermatitis symptoms. It can be ingested as a supplement to make.
  • the carbon when used as an additive of a health functional food, it can be added as it is or used with other foods or food ingredients, and is usually It can be used appropriately according to the method of phosphorus.
  • the mixing amount of the active ingredient can be appropriately determined according to each purpose of use, such as prevention, health or treatment.
  • Formulations of health functional foods may be in the form of powders, granules, pills, tablets, capsules, as well as general foods or beverages.
  • the type of food is not particularly limited, and examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, and dairy products including ice cream. , Various soups, beverages, teas, drinks, alcoholic beverages and vitamin complexes, and may include all foods in the usual sense.
  • the carbon when preparing food or beverage, may be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less based on 100 parts by weight of the raw material.
  • the amount in the case of long-term intake for the purpose of health and hygiene or for the purpose of health control, the amount may be less than the above range, and the present invention has no problem in terms of safety in terms of using fractions from natural products. It can also be used in the above amount.
  • the beverage may contain various flavoring agents or natural carbohydrates as an additional component, like a conventional beverage.
  • the natural carbohydrates described above may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • sweetener natural sweeteners such as taumatin and stevia extract, and synthetic sweeteners such as saccharin and aspartame can be used.
  • the ratio of the natural carbohydrate may be about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the beverage according to the present invention.
  • the health functional food for the prevention or improvement of allergic diseases or atopic dermatitis includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloids. It may contain thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages.
  • the health functional food composition for preventing or improving allergic diseases or atopic dermatitis of the present invention may contain flesh for the manufacture of natural fruit juice, fruit juice drink, and vegetable drink. These ingredients may be used independently or in combination. The ratio of these additives is not limited, but it is generally selected from 0.01 to 0.1 parts by weight based on 100 parts by weight of the functional food of the present invention.
  • cosmetic composition used in the present invention is a composition including the compound, and the formulation may be in any form.
  • cosmetic products prepared using the above composition include creams such as nutritional cream, eye cream, massage cream, cleansing cream, packs, lotions such as nutritional lotion, essences, softening lotion, lotion such as nutritional lotion.
  • lotions such as nutritional lotion, essences, softening lotion
  • lotion such as nutritional lotion.
  • Types, powders, foundations, makeup bases, and the like and can be manufactured and commercialized in any of these formulations to achieve the object of the present invention, and are not limited to the above examples.
  • the cosmetic composition according to the present invention can be formulated by a conventional cosmetic preparation method.
  • the cosmetics of the present invention are skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, essence, pack, mask pack, mask sheet , Soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, emulsion, press powder, loose powder, and eye shadow.It may have any one formulation selected from the group consisting of.
  • the cosmetic composition of the present invention may contain other additives such as excipients, carriers, etc. in addition to carbon or salts thereof, and it is possible to apply and mix ordinary ingredients to be blended in general skin cosmetics as needed.
  • the cosmetic composition of the present invention may further include a transdermal penetration enhancer.
  • a transdermal penetration enhancer is a composition that allows a desired component to penetrate into blood vessel cells of the skin at a high absorption rate.
  • phospholipid components, liposome components, and the like used in lecithin cosmetics are included, but are not limited thereto.
  • an oil that can be mainly used as an oily component at least one selected from vegetable oils, mineral oils, silicone oils, and synthetic oils may be used. More specifically, mineral oil, cyclomethicone, squalane, octyldodecyl myristate, olive oil, Vitis vinifera seed oil, macadamia nut oil, glyceryl octanoate, castor oil, ethylhexyl isononanoate, dime Chicon, cyclopentasiloxane, and sunflower seed oil can be used.
  • a surfactant a higher alcohol, and the like may be added to reinforce the emulsifying ability.
  • conventional surfactants such as nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, phospholipids, etc.
  • sorbitansquinoleate polysorbate 60
  • Glyceryl stearate lipophilic glyceryl stearate
  • sorbitan oleate sorbitan stearate
  • DIA-cetylphosphate sorbitan stearate/sucrosecoate
  • glyceryl stearate/polyethylene glycol-100 Stearate ceteareth-6 olivate
  • arachidyl alcohol/behenyl alcohol/arachidyl glucoside polypropylene glycol-26-butes-26/polyethylene glycol-40 hydrogenated castor oil, etc.
  • an alcohol having 12 to 20 carbon atoms such as cetyl alcohol, stearyl alcohol, octyldodecanol, isostearyl alcohol, and the like may be used alone or in combination of one or more.
  • the aqueous phase component may further add 0.001 to 5% by weight of one or more thickeners such as carbomer, xanthan gum, bentonite, magnesium aluminum silicate, cellulose gum, dextrin palmitate, etc. to adjust the viscosity or hardness of the aqueous phase.
  • thickeners such as carbomer, xanthan gum, bentonite, magnesium aluminum silicate, cellulose gum, dextrin palmitate, etc.
  • the cosmetic composition of the present invention includes medicinal ingredients such as higher fatty acids and vitamins, sunscreen, and antioxidants (butylhydroxyanisole, propyl gallic acid, lysorbic acid, tocopheryl acetate, butylated hydroxy) as needed.
  • medicinal ingredients such as higher fatty acids and vitamins, sunscreen, and antioxidants (butylhydroxyanisole, propyl gallic acid, lysorbic acid, tocopheryl acetate, butylated hydroxy) as needed.
  • preservatives methylparaben, butylparaben, propylparaben, phenoxyethanol, imidazolidinylurea, chlorphenesin, etc.
  • colorants pH adjusters (triethanolamine, citric acid, citric acid, sodium citrate, malic acid, etc.) Sodium Malate, Pmalic Acid, Sodium Fmalate, Succinic Acid, Sodium Succinate, Sodium Hydroxide, Sodium Monohydrogen Phosphate, etc.), Moisturizing Agents (Glycerin, Sorbitol, Propylene Glycol, Butylene Glycol, Hexylene Glycol, Diglycerin , Betaine, glyceres-26, methylgluces-20, etc.), lubricants and the like can be added.
  • the cosmetic composition of the present invention further includes a substance capable of auxiliaryly providing essential nutrients to the skin, preferably, it may contain a natural scent, a cosmetic scent, or an auxiliary agent including, but not limited to, herbal medicines. have.
  • the effective content of carbon or a cosmetically acceptable salt thereof in the cosmetic composition of the present invention is not particularly limited, and may be included in an amount of 0.0001 to 20% by weight based on the total weight of the composition. Less than 0.0001% by weight of carbon or a salt thereof in the cosmetic may not have an expected improvement effect due to its small dose, and more than 20% by weight of carbon or a salt thereof may exhibit known toxicity.
  • fragment composition of the present invention may be formulated as a base for skin external use such as perfume, cosmetics, and bath, or food, pharmaceuticals, etc., and the blending amount is appropriately selected in order to achieve the desired effect according to conventional techniques in the art. Can be blended.
  • the formulation of the perfume composition of the present invention is not particularly limited, but may be any one selected from powder, granule, liquid spray, solid and gel type formulations.
  • the perfume composition includes cosmetic products including perfume, soap cleaning products including bath soap, indoor cleaning products including glass cleaners, fragrance products including car air fresheners, bath products including herbal bath products, and stationery It can be used to manufacture a fragrance product, an environmental product including an office fragrance, or an industrial product including a synthetic resin.
  • the perfume composition of the present invention contains the active ingredient, carbon, based on the total weight of the perfume composition, from 0.00001% to 10% by weight, preferably from 0.00001% by weight, depending on the product type in which the perfume composition of the present invention is embodied. It may contain 1.0% by weight, more preferably in the range of 0.00001% by weight to 0.5% by weight.
  • fragrance composition examples include soap, cosmetics, bath agents, aroma oils, etc., specifically body lotion, shampoo, hair rinse, hair conditioner, hair treatment, antiperspirant, skin lotion, skin cream, deodorant , Perfume (spray or fumigant), lipstick, lip cream, bath agent, etc., but are not limited thereto.
  • These products may contain various additives such as blood circulation accelerators, anti-inflammatory agents, moisturizing agents, astringents, inorganic salts, organic salts, oily ingredients, surfactants, herbal medicines, colors, fragrances, sulfur, sinter deposits, disinfectants, etc. .
  • the perfume composition of the present invention will generally be used as an external application for the skin of cosmetic formulations such as makeup products, skin lotions, and skin creams.
  • cosmetic formulations such as makeup products, skin lotions, and skin creams.
  • it may contain ingredients commonly used in these cosmetic formulations.
  • the perfume composition of the present invention is preferably used by being incorporated into a bathing agent in that the active ingredient, carbon, has atopic dermatitis improving activity.
  • the active ingredient may preferably be included in the range of 0.00001 to 1% by weight, more preferably 0.0001 to 0.1% by weight, based on the total weight of the bath agent.
  • the bathing agent may be added to the bath water in a concentration of 0.015 to 15 ppm and used.
  • the bath agent may contain inorganic salts, organic acids, oily ingredients, etc. in addition to the active ingredients of the perfume composition of the present invention.
  • sodium chloride, sodium hydrogen carbonate, sodium carbonate, borax, sodium sulfate, sodium sulfide, sodium sesquicarbonate, sodium nitrate, sodium thiosulfate, sodium polyphosphate, sodium phosphate, calcium oxide, magnesium oxide, calcium carbonate, magnesium carbonate, potassium chloride, sulfide Potassium and the like may be exemplified, and these may be used alone or as a mixture of two or more.
  • These inorganic salts may be added to the bath agent in an amount of 5% by weight or more, preferably 10% by weight or more, based on the total weight of the bath agent.
  • organic acid succinic acid, fumaric acid, malic acid, tartaric acid, citric acid, benzoic acid and the like can be exemplified, and these may be used alone or in a mixture of two or more. These organic acids may be added to the bath agent in the range of 0.1 to 50% by weight, based on the total weight of the bath agent.
  • oily component examples include wax, hydrocarbon, higher fatty acid, higher alcohol, ester, and silicone oil.
  • the bath agent may also contain additional ingredients commonly used in the art.
  • these components include inorganic acids such as boric acid, metasilicic acid, and silicic anhydride; Herbal powders such as fennel, ginkgo, ginger, citrus peel, valerian root, mint, ginseng, and oats; Natural pigments, such as coal tar dye, chlorophyll, riboflavin, safflower, and anthraquinone, which have been found to be harmless to the human body; Vitamins such as vitamin A, vitamin C, vitamin D, and vitamin E; Sulfur, mica powder, clay powder, loess powder, rice bran carbide, fungicides, and preservatives.
  • inorganic acids such as boric acid, metasilicic acid, and silicic anhydride
  • Herbal powders such as fennel, ginkgo, ginger, citrus peel, valerian root, mint, ginseng, and oats
  • Natural pigments such as coal tar dye,
  • bathing agents may be prepared in any form such as granules, tablets, liquids, powders, and the like.
  • quasi-drug refers to items that are less effective than medicines among items used for the purpose of diagnosing, treating, improving, alleviating, treating or preventing diseases of humans or animals. According to this, quasi-drugs exclude items used for pharmaceutical purposes, and include products used for the treatment or prevention of diseases of humans and animals, and products that have mild or no direct action on the human body.
  • the quasi-drug composition of the present invention is used for the purpose of preventing or improving allergic diseases or atopic dermatitis, and is not particularly limited in its formulation, for example, softening lotion, nutritional lotion, massage cream, nutrition cream, pack , A mask pack, a mask sheet, a gel or a cosmetic composition having a skin adhesive type cosmetic formulation, and may be a transdermal dosage form such as a lotion, ointment, gel, cream, patch, or spray.
  • the quasi-drug composition may be arbitrarily selected and blended according to the formulation or purpose of use of other quasi-drugs.
  • the mixing amount of the active ingredient may be appropriately determined depending on the purpose of use (inhibition or mitigation).
  • thickeners, stabilizers, solubilizers, conventional adjuvants such as vitamins, pigments and flavors, and carriers may be included.
  • the content of the carbon or salt thereof of the present invention is preferably 0.0001 to 20% by weight, respectively, based on the total weight of the quasi-drug composition. If it exceeds 20% by weight, color and stability may be deteriorated during the preparation of the composition, and if it is less than 0.0001%, the effect is negligible.
  • components other than the essential components described above may be appropriately selected and blended by a person skilled in the art without difficulty depending on the formulation or purpose of use.
  • Mast cells (rat basophilic leukemia cell line, RBL-2H3) were purchased and used from ATCC (Manassas, VA, USA).
  • DMEM Disbecco modified eagle medium
  • FBS heat-inactivated feta bovine serum
  • penicillin and streptomycin Gibco BRL, USA
  • Cells were cultured in the culture medium. Cells were cultured under conditions of 37° C. and 5% CO 2 for experiments.
  • the mast cells were suspended in DMEM containing 10% FBS and then dispensed into a 6 well plate (Corning, USA) to a cell number of 1 ⁇ 10 6 cells/ml.
  • DNP-HSA dinitrophenylated human serum albumin; 100 ng/ml
  • anti-DNP (dinitrophenyl)-IgE was treated and carboxylic (100 ⁇ M) was treated and incubated for 24 hours, and then an immune response was induced with DNP-HSA.
  • negative control cells they were treated with DMSO instead of carbon and incubated for 24 hours, and then an immune response was induced with DNP-HSA.
  • Keratinocytes human keratinocyte cell line, HaCaT
  • ATCC Manassas, VA, USA
  • Cells were cultured using a DMEM culture medium containing 10% FBS (fetal bovine serum) and antibiotics.
  • FBS fetal bovine serum
  • a 75T-flask and a 6-well plate were used as the culture vessel, and cultured in a 37°C incubator supplied with 5% CO2. The culture medium was changed every 3 to 4 days, and when cells were excessively proliferated, they were subcultured.
  • the dispensed HaCaT cells (5 ⁇ 10 5 /well) were cultured for 24 hours and washed with PBS.
  • TNF- ⁇ tumor necrosis factor- ⁇
  • IFN- ⁇ interferon gamma
  • the immune reaction was terminated by standing in an ice bath for 10 minutes, and the culture was centrifuged at 10,000 xg for 10 minutes, and the supernatant was taken. Transferred to a 96-well plate. Histamine was quantified using ENZO's histamine release assay ELISA kit, and was measured at 450 nm wavelength of Infinite M200 pro microplate reader (TECAN).
  • RT-PCR was reacted at 45°C for 30 minutes and 94°C for 5 minutes using a one-step RT-PCR PreMix kit (iNtRON Biotechnology, Korea), followed by denaturation at 94°C for 30 seconds, and 30 at 55°C. After annealing for a second, the cycle of stretching at 72°C for 1 minute was repeated 32 times, and the last extension was performed at 72°C for 5 minutes, followed by PiQ SYBR green supermix (Bio-Rad ) And CFX ConnectTM Real-Time PCR Detection System (Bio-Rad) were used to perform quantitative PCR, and the primer sequence used at this time is as shown in [Table 1].
  • the concentration of histamine in the cell culture was measured by the enzyme immunoreaction method.
  • the histamine concentration was significantly increased in control cells sensitized with anti-DNP (dinitrophenyl)-IgE and induced an immune response with DNP-HSA compared to normal mast cells.
  • the concentration of histamine was significantly reduced (FIG. 1).
  • compositions of Preparation Examples 1 to 3 were prepared according to the following composition and composition ratio using carbon having excellent preventive and therapeutic (or preventive and improving effect) effect of the allergic disease or atopic dermatitis. It was prepared according to a conventional method.
  • the above ingredients were mixed and filled in an airtight cloth to prepare a powder.
  • tablets were prepared by tableting according to a conventional tablet preparation method.
  • the capsules were prepared by filling them into gelatin capsules according to a conventional capsule preparation method.
  • the above ingredients are dissolved by adding each ingredient to purified water according to a conventional manufacturing method, added an appropriate amount of lemon flavor, adjusted to 100 mL by adding purified water, sterilized, and filled in a brown bottle to prepare a liquid formulation.
  • Vitamin A acetate 70 ⁇ g
  • Vitamin B 1 0.13 mg
  • Vitamin B 2 0.15 mg
  • Vitamin B 6 0.5 mg
  • Vitamin B 12 0.2 ⁇ g
  • composition ratio of the vitamin and mineral mixture is relatively suitable for health food, but it may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method.
  • Granules can be prepared, and used for preparing health food compositions according to a conventional method.
  • composition ratio is a mixture of ingredients suitable for a relatively preferred beverage in a preferred embodiment, but the mixing ratio may be arbitrarily modified according to regional and ethnic preferences such as the demand class, the country of demand, and the purpose of use.
  • the above blending ratio is a mixture of ingredients suitable for a relatively nutrient lotion in a preferred embodiment, but the blending ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
  • the above blending ratio is a mixture of ingredients suitable for a relatively soft lotion in a preferred embodiment, but the blending ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
  • the above blending ratio is a mixture of ingredients suitable for a nutritional cream in a preferred embodiment, but the blending ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
  • the above blending ratio is a mixture of ingredients suitable for a massage cream in a preferred embodiment, but the blending ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
  • the above blending ratio is a mixture of ingredients suitable for the pack in a preferred embodiment, but the blending ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
  • the above blending ratio is a mixture of ingredients suitable for a gel in a preferred embodiment, but the blending ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
  • the above blending ratio is a mixture of ingredients suitable for a cosmetic composition in a preferred embodiment, but can be applied to cosmetics for various purposes including other colored cosmetics, and a drug that can be applied thinly to the human body according to its efficacy, that is, It can be used for manufacturing as an ointment, and the blending ratio can be arbitrarily modified according to regional and ethnic preferences such as the demand class, the country of demand, and the purpose of use.

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Abstract

La présente invention concerne une composition pour la prévention ou le traitement de maladies allergiques ou de la dermatite atopique comprenant de la carvone comme principe actif. La composition comprenant de la carvone comme principe actif selon la présente invention a pour effet d'atténuer la dermatite atopique provoquée par une réaction allergique et peut être utilisée comme composition pour la prévention ou le traitement de diverses maladies allergiques en réduisant une réaction inflammatoire.
PCT/KR2020/010976 2019-08-19 2020-08-18 Composition pour la prévention ou le traitement d'une maladie allergique ou de la dermatite atopique comprenant de la carvone ou un sel associé comme principe actif WO2021034080A1 (fr)

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KR10-2019-0101054 2019-08-19
KR1020190101054A KR102076938B1 (ko) 2019-08-19 2019-08-19 카르본 또는 이의 염을 유효성분으로 포함하는 알러지성 질환 또는 아토피 피부염 예방 또는 치료용 조성물

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20060054807A (ko) * 2004-11-16 2006-05-23 박명호 아토피 피부 개선용 화장료
US20060275516A1 (en) * 2005-06-02 2006-12-07 Ram A N S Compositions and methods for the treatment of allergic rhinitis
JP2010260855A (ja) * 2009-04-08 2010-11-18 Lion Corp 気道異物除去剤及び気道異物除去用組成物
US20100305214A1 (en) * 2007-09-26 2010-12-02 Aisa Therapeutics Use of a Monoterpene to Increase Tissue Repair
US20140249234A1 (en) * 2011-06-07 2014-09-04 Frederic J. Burns Compositions and Methods for Restoring the Stratum Corneum and Treating Dermatological Diseases

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20180128602A (ko) 2017-05-24 2018-12-04 한남대학교 산학협력단 나복근 즙을 유효성분으로 함유하는 아토피 피부염의 예방, 개선 또는 치료용 조성물

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20060054807A (ko) * 2004-11-16 2006-05-23 박명호 아토피 피부 개선용 화장료
US20060275516A1 (en) * 2005-06-02 2006-12-07 Ram A N S Compositions and methods for the treatment of allergic rhinitis
US20100305214A1 (en) * 2007-09-26 2010-12-02 Aisa Therapeutics Use of a Monoterpene to Increase Tissue Repair
JP2010260855A (ja) * 2009-04-08 2010-11-18 Lion Corp 気道異物除去剤及び気道異物除去用組成物
US20140249234A1 (en) * 2011-06-07 2014-09-04 Frederic J. Burns Compositions and Methods for Restoring the Stratum Corneum and Treating Dermatological Diseases

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