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WO2020242010A1 - Composition pharmaceutique pour la prévention ou le traitement de la dermatite atopique, contenant un produit de fermentation de carica papaya linn. - Google Patents

Composition pharmaceutique pour la prévention ou le traitement de la dermatite atopique, contenant un produit de fermentation de carica papaya linn. Download PDF

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Publication number
WO2020242010A1
WO2020242010A1 PCT/KR2020/001739 KR2020001739W WO2020242010A1 WO 2020242010 A1 WO2020242010 A1 WO 2020242010A1 KR 2020001739 W KR2020001739 W KR 2020001739W WO 2020242010 A1 WO2020242010 A1 WO 2020242010A1
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Prior art keywords
papaya
atopic dermatitis
fermented product
preventing
composition
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Ceased
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PCT/KR2020/001739
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English (en)
Korean (ko)
Inventor
조명행
이아영
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SNU R&DB Foundation
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Seoul National University R&DB Foundation
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/065—Microorganisms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • 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
    • A23V2200/318—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
    • A23V2250/20—Natural extracts
    • A23V2250/21—Plant extracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10—Preparation or pretreatment of starting material
    • A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/85—Products or compounds obtained by fermentation, e.g. yoghurt, beer, wine

Definitions

  • the present invention relates to a pharmaceutical composition for the prevention or treatment of atopic dermatitis comprising a papaya fermented product, a quasi-drug composition for the prevention or improvement of atopic dermatitis, a food composition or a cosmetic composition.
  • Atopic dermatitis is a commonly occurring chronic inflammatory skin disease.It increases the number of eosinophils, increases serum IgE levels, and is a proinflammatory cytokine including TNF- ⁇ and chemokine. cytokine).
  • the IgE induces mast cells activation, and accordingly, an inflammatory mediator including histamine, Th2 cytokines such as IL-4, IL-5, and IL-13 It is released from mast cells.
  • the secretion of IgE is the most important and immediate hypersensitivity reaction of atopic dermatitis.
  • Atopic dermatitis in dogs and cats begins with scratching at the age of 1 year old, and develops into typical symptoms such as skin redness, pustules and crust formation, along with scratching at the age of 3, and it is known that ear disease accompanies most of this.
  • Papaya ( Carica papaya Linn. ) is one of the most popular and widely cultivated tropical plants, and has traditionally been used for nutritional and medicinal purposes. According to the literature, papaya has been reported to be effective in cardiovascular disease, dengue fever, digestive disorders, inflammatory diseases, wound healing, malaria, hypoglycaemia, and hyperlipidaemia. In addition, papaya contains active compounds having anticancer activity such as ⁇ -tocopherol, flavonoid, benzylisothiocyanate, and lycopene.
  • the present inventors studied to develop a therapeutic agent for atopic dermatitis using natural products. As a result, it was confirmed that the papaya fermented product obtained by fermenting papaya with lactic acid bacteria can cure atopic dermatitis by suppressing the immune response. Was completed.
  • a pharmaceutical composition for the prevention or treatment of atopic dermatitis comprising a papaya fermented product, a quasi-drug composition for preventing or improving atopic dermatitis, a food composition, and a cosmetic composition.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of atopic dermatitis comprising a papaya fermented product.
  • the present invention provides a quasi-drug composition for preventing or improving atopic dermatitis comprising a papaya fermented product.
  • the present invention provides a food composition for preventing or improving atopic dermatitis comprising a papaya fermented product.
  • the present invention provides a cosmetic composition for preventing or improving atopic dermatitis comprising a papaya fermented product.
  • the present invention provides a method for preventing or treating atopic dermatitis comprising a step of treating a papaya fermented product to a mammal.
  • the present invention provides a method for preparing a pharmaceutical product for preventing or treating atopic dermatitis comprising a step of preparing a composition comprising a papaya fermented product.
  • the papaya fermentation product according to the present invention not only has almost no side effects using the natural papaya, but also effectively reduces the number of skin lesions and mast cells, and pays attention to the levels of NF- ⁇ B and I ⁇ B ⁇ in the cytoplasm involved in the expression of inflammatory genes. It is expected to be useful in the development of pharmaceuticals, health functional foods and cosmetics for the prevention, improvement or treatment of atopic dermatitis.
  • 1 is a diagram showing the overall experimental protocol of a mouse experiment using the papaya fermentation product of the present invention.
  • Figure 2 is a diagram showing the observation results of the degree of improvement of atopic dermatitis for each group as a photograph.
  • 3 is a graph showing the observed results of the degree of improvement of atopic dermatitis for each group by quantifying clinical skin severity scores (*P ⁇ 0.05, **P ⁇ 0.01, ***P ⁇ 0.001 vs. control group; ###P) ⁇ 0.001 vs. DNCB group; $$P ⁇ 0.01 vs. papaya fermentation and DNCB+ papaya fermentation group).
  • FIG. 4 is a diagram showing the results of observing the degree of improvement of atopic dermatitis according to the papaya fermentation treatment of the present invention through histological analysis.
  • 4A, B, and C are diagrams showing the results of H&E, toluidine blue, and Giemsa staining, respectively
  • FIG. 4D is a diagram showing the results of measuring the thickness of the epidermis, and E and F of FIG. 4 are in the mouse dermis.
  • Is a diagram showing the results of counting the number of mast cells and eosinophils (*P ⁇ 0.05, **P ⁇ 0.01, ***P ⁇ 0.001 vs. control group; #P ⁇ 005, ##P ⁇ 0.01, ### P ⁇ 0.001 vs. DNCB group).
  • FIG. 5 is a diagram showing the results of observing changes in IgE and IgG levels of mice according to the papaya fermentation treatment of the present invention.
  • 5A and B are diagrams showing changes in serum IgE and IgG levels
  • FIG. 5C and D are diagrams showing changes in IgE and IgG secretion levels in spleen cells (*P ⁇ 0.05, **P ⁇ 0.01, * **P ⁇ 0.001 vs. control group; #P ⁇ 005, ###P ⁇ 0.001 vs. DNCB group; $P ⁇ 0.05, $$$P ⁇ 0.001 vs. papaya fermented product and DNCB+ papaya fermented product group).
  • FIG. 6 is a diagram showing the results of observing changes in the expression levels of IL-10, IFN- ⁇ , and inflammatory proteins according to the papaya fermentation treatment of the present invention.
  • 6A, B, D, and E are diagrams showing changes in the expression levels of IL-10, IFN- ⁇ , NF- ⁇ B and I ⁇ B ⁇ , respectively, and C of FIG. 6 shows Western blot results for NF- ⁇ B and I ⁇ B ⁇ .
  • Fig. (*P ⁇ 0.05, **P ⁇ 0.01 vs. control group; #P ⁇ 005, ##P ⁇ 0.01 vs. DNCB group).
  • the present invention provides a pharmaceutical composition for the prevention or treatment of atopic dermatitis comprising a papaya fermented product.
  • atopic dermatitis or “atopic skin disease” refers to a skin disease accompanied by pruritus (itch), dry skin, and characteristic eczema as a chronic and recurrent inflammatory skin disease that begins mainly in infancy or childhood. In infancy, it starts with eczema on the spread side of the face and limbs, but as it grows, it appears in the form of eczema on the bending part of the arm and the bend behind the knee. . In adults, lichenification occurs in which the skin at the folds becomes thick, and eczema on the face is more common than in childhood.
  • treatment refers to any act of improving or beneficially altering the symptoms of atopic dermatitis by administering or applying the composition.
  • Those of ordinary skill in the technical field to which the present application pertains will know the exact criteria of atopic dermatitis or disease in which the composition of the present application is effective, and determine the degree of improvement, improvement and treatment by referring to the data presented by the Korean Medical Association. I will be able to.
  • prevention refers to any action that suppresses or delays the onset of diseases for which the present composition is effective by administration of the composition according to the present invention. It will be apparent to those skilled in the art that the composition of the present application, which is effective for the treatment of atopic dermatitis, can prevent such diseases if taken before the initial symptoms or onset of related diseases.
  • Atopic dermatitis is not only spreading to adults due to environmental pollution, stress, and changes in residential environment, but also due to the increase in the elderly population complaining of dry skin, the atopic market is rapidly growing.
  • various kinds of skin disease treatments are currently on the market, but most of these drugs are artificially synthesized, and when used for a long time, they cause serious side effects or cause resistance of pathogens, so that the expected therapeutic effect cannot be obtained. Therefore, it would be said that the economic and industrial importance of the technology for manufacturing functional products for skin disease improvement from natural materials is very significant. Accordingly, the present inventors prepared a papaya fermented product by fermenting natural products such as papaya and pomegranate with lactic acid bacteria, and confirmed the excellent therapeutic effect on atopic dermatitis, thereby completing the present invention.
  • the papaya fermented product may be a fermented product of a papaya extract and pomegranate mixture, and 1 to 10 parts by weight, preferably 1 to 5 parts by weight, of lactic acid bacteria based on 100 parts by weight of the papaya extract and pomegranate mixture, More preferably, 1 to 3 parts by weight, most preferably 2 parts by weight of inoculation, and fermentation may be characterized in that prepared.
  • the papaya extract and pomegranate mixture may be prepared by mixing papaya extract and pomegranate fruit, then adding fructooligosaccharide at the same weight as the mixed papaya extract and pomegranate fruit, and mixing evenly. That is, the papaya extract and pomegranate mixture may be prepared by mixing papaya extract, pomegranate and fructooligosaccharide in a ratio of 1:1:2 (w/w).
  • the fermentation may be performed at 25° C. to 40° C. for 1 to 5 days, preferably at 30° C. to 40° C. for 2 to 4 days. In one embodiment of the present invention, at 37° C. Fermented for 3 days to prepare a papaya fermented product according to the present invention.
  • the term "papaya extract” refers to an extract obtained by extracting papaya, preferably papaya leaves and fruits.
  • the papaya extract is water, an alcohol having 1 to 4 carbon atoms, or a mixture thereof It is characterized by being extracted with a solvent.
  • the water may be hot water of 90°C to 130°C, preferably 100°C to 120°C, more preferably 105°C to 115°C.
  • the hot water extraction method can avoid the extraction of steroids, fat-soluble vitamins, and protein-based substances, and the extraction process is also simpler than the organic solvent and the time required is also short, so it has many advantages over the organic solvent extraction method.
  • the extract may include an extract obtained by an extraction treatment, a dilution or concentrate of the extract, a dried product obtained by drying the extract, or any of these preparations or purified products.
  • the papaya extract may be extracted from at least one selected from the group consisting of papaya leaves, stems, roots, and fruits, and preferably extracted from papaya leaves, fruits, or a mixture of leaves and fruits. Can be used.
  • the lactic acid bacteria inoculated in the papaya extract and pomegranate are Lactobacillus acidophilus , Lactobacillus casei , Lactobacillus plantarum , Lactobacillus Bvlgari Cous ( Lactobacillus bulgaricus ), Lactobacillus lactis , Lactobacillus fermentum , Bifidobacterium bifidum , Saccharomyces cerevisidae and Saccharomyces cerevisidae It may be characterized in that at least one selected from the group consisting of Saccharomyces boulardii , and preferably all of the lactic acid bacteria are inoculated to obtain the papaya fermented product according to the present invention.
  • composition comprising the papaya fermented product according to the present invention may be characterized in that it further comprises vegetable glycerin.
  • the vegetable glycerin may be added in an appropriate amount according to the purpose of the invention by a person skilled in the art, and for example, a papaya fermented product may be mixed with 94 to 96 parts by weight and 4 to 6 parts by weight of vegetable glycerin.
  • the composition comprising the papaya fermented product according to the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stable It may contain additives such as an agent, a preservative, an alcohol, and a carbonation agent used in carbonated beverages. These ingredients may be used independently or in combination, and the ratio of these additives is not very important, but it is generally selected from 0.01 to 0.1 parts by weight per 100 parts by weight of the papaya fermentation.
  • the pharmaceutical composition may further include an appropriate carrier, excipient, or diluent commonly used in the preparation of a pharmaceutical composition.
  • the composition is a tablet, pill, powder, granule, capsule, suspension, solution, emulsion, syrup, sterilized aqueous solution, non-aqueous solvent, suspension, emulsion, freeze-dried preparation, transdermal absorbent, gel, lotion, Ointments, creams, patches, cataplasmas, pastes, sprays, skin emulsions, skin suspensions, transdermal delivery patches, drug-containing bandages and suppositories may have any one formulation selected from the group consisting of, oral or It may be a variety of parenteral formulations, but is not limited thereto.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations include at least one excipient, such as starch, calcium carbonate, sucrose, or lactose ( lactose), gelatin, etc.
  • excipients such as starch, calcium carbonate, sucrose, or lactose ( lactose), gelatin, etc.
  • lubricants such as magnesium stearate and talc are also used.
  • Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups.In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as humectants, sweeteners, fragrances, and preservatives may be included. have.
  • Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories.
  • the non-aqueous solvent and the suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used.
  • a base for suppositories witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogelatin, and the like can be used.
  • the pharmaceutical composition of the present invention can be administered to mammals such as dogs, cats, mice, livestock, humans, etc. by various routes such as oral or parenteral, such as oral, rectal, intravenous, muscle, subcutaneous, intrauterine, dural It can be administered by intracranial or intraventricular injection.
  • the preferred dosage of the pharmaceutical composition varies depending on the condition and weight of the patient, the degree of disease, the form of the drug, the route and duration of administration, but may be appropriately selected by those skilled in the art.
  • the papaya fermented product of the present invention is preferably administered at 0.0001 to 100 mg/kg per day, preferably 0.001 to 100 mg/kg, and the administration may be administered once a day. Alternatively, it may be administered several times.
  • the pharmaceutical composition according to the present invention is characterized in that it can be applied to companion animals, such as dogs and cats, particularly having atopic dermatitis (or hypersensitivity dermatitis).
  • the present invention provides a method for preventing or treating atopic dermatitis comprising a step of treating a papaya fermented product to a mammal.
  • the present invention provides a method for producing a pharmaceutical product for preventing or treating atopic dermatitis comprising a step of preparing a composition comprising a papaya fermented product.
  • the present invention provides a quasi-drug composition for preventing or improving atopic dermatitis comprising a papaya fermented product.
  • quadsi-drug refers to non-instrument, machine or device among articles used for the purpose of diagnosing, treating, alleviating, treating or preventing diseases of humans or animals, and pharmacological effects on the structure and function of humans or animals It refers to any item that is not an apparatus, machine, or device among the items used for the purpose of giving a message.
  • the quasi-drug composition is not particularly limited thereto, but preferably may be a disinfectant cleaner, a shower foam, a gagrin, a wet tissue, a detergent soap, a hand wash, a humidifier filler, a mask, an ointment or a filter filler.
  • the quasi-drug composition may include skin external preparations and personal hygiene products.
  • the external preparation for skin is not particularly limited thereto, but preferably may be prepared and used in the form of an ointment, lotion, spray, patch, cream, powder, suspension, gel or gel, and the personal hygiene product is specially used thereto.
  • the present invention provides a food composition for preventing or improving atopic dermatitis comprising a papaya fermented product.
  • the "food composition” may include all foods in a conventional sense, and may be mixed with terms known in the art, such as functional foods and health functional foods.
  • the papaya fermented product of the present invention When used as a food additive, the papaya fermented product may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method.
  • the mixing amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment), and may further include food additives acceptable for food. Since the composition of the present invention uses a substance derived from a natural substance as an active ingredient, there is no problem in terms of stability, and there is no significant limitation on the amount of mixing.
  • “functional food” means a food manufactured and processed using raw materials or ingredients having useful functions for the human body according to the Health Functional Food Act No. 6727, and “functional” It means ingestion for the purpose of obtaining useful effects for health purposes such as controlling nutrients for structure and function or for physiological effects.
  • health functional food refers to a food manufactured and processed by extracting, concentrating, refining, mixing, or extracting, concentrating, refining, or mixing a specific ingredient as a raw material for the purpose of health assistance. .
  • the food composition comprising the fermented papaya of the present invention as an active ingredient may be prepared by mixing suitable other auxiliary ingredients and known additives that may be contained in food according to the choice of a person skilled in the art.
  • suitable other auxiliary ingredients and known additives include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and
  • vitamins complexes and the like can be prepared by adding the papaya fermented product according to the present invention as a main component to juice, tea, jelly, and juice.
  • foods that can be applied to the present invention include, for example, special nutritional foods (e.g., formula, infants, baby food, etc.), processed meat products, fish meat products, tofu, rice cakes, noodles (e.g., ramen, noodles, etc.), health supplements. , Seasoned foods (e.g. soy sauce, miso, red pepper paste, mixed sauce, etc.), sauces, sweets (e.g. snacks), dairy products (e.g. fermented milk, cheese, etc.), other processed foods, kimchi, pickles (various kimchi, pickles, etc.) ), beverages (eg fruit, vegetable beverages, soy milk, fermented beverages, etc.), natural seasonings (eg, ramen soup, etc.).
  • special nutritional foods e.g., formula, infants, baby food, etc.
  • processed meat products e.g., fish meat products, tofu, rice cakes, noodles (e.g., ramen, noodles, etc.), health supplements.
  • the health functional food composition of the present invention When used in the form of a beverage, it may contain various sweetening agents, flavoring agents, natural carbohydrates, and the like as an additional component, like a normal beverage.
  • the health functional food composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin , Alcohol, carbonated beverages, etc. may contain.
  • it may contain flesh for the manufacture of natural fruit juice, fruit juice beverage and vegetable beverage.
  • the present invention provides a cosmetic composition for preventing or improving atopic dermatitis comprising a papaya fermented product.
  • the papaya fermented product according to the present invention is a natural substance that is safe in the body, softening lotion, astringent lotion, nutritional lotion, nutrition cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, powder , Body lotion, body cream, body oil, body essence, makeup base, foundation, hair dye, shampoo, conditioner or body cleaner, etc., but is not limited thereto.
  • additional substances may be added according to the formulation of external preparations for skin or cosmetics.
  • the formulation is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or Zinc oxide or the like may be used, and when the formulation is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component.
  • Propellants such as chlorofluorohydrocarbon, propane/butane or dimethyl ether.
  • a solvent, a solubilizing agent or an emulsifying agent is used as a carrier component, preferably water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan, but is not limited thereto.
  • a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, Aluminum metahydroxide, bentonite, agar, or tracant
  • a surfactant containing cleansing as a carrier component, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, Imidazolinium derivatives, methyltaurates, sarcosinates, fatty acid amide ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, or ethoxylated
  • the papaya extract and pomegranate were mixed at a ratio of 1:1 (w/w), respectively, and fructooligosaccharide was added at the same weight as the mixed papaya extract and pomegranate, and mixed evenly.
  • the mixture was finely pulverized with a grinder to prepare papaya blue. Thereafter, 2 parts by weight of lactic acid bacteria are inoculated with respect to 100 parts by weight of the prepared papaya green, and the lactic acid bacteria are mixed in equal amounts of 9 types of lactic acid bacteria and cultured at 37°C for 3 days to obtain 6 x 10 8 cfu/mL. Was prepared.
  • the papaya fermentation product was freeze-dried and stored at 4°C until use.
  • the lactic acid bacteria used in the preparation of the papaya fermentation product were as follows: Lactobacillus acidophilus (KCCM 32820), Lactobacillus casei ; KCCM 12452), Lactobacillus plantarum ( KCCM 11322), Lactobacillus bulgaricus ( KCCM 35463), Lactobacillus lactis ( KCCM 34717), Lactobacillus fermentum ( Lactobacillus fermentum; KCCM 34717) KCCM 40400), Bifidobacterium bifidum ( KCCM12096), Saccharomyces cerevisidae ( KCCM 11215) and Saccharomyces boulardii ( Saccharomyces boulardii; ATCC MYA-796 ).
  • Papaya extract is an extract of papaya leaf and fruit, purchased from STRAYA NATURAL Pharm (Sydney, Australia). Pomegranate fruit was purchased and used on the market.
  • the prepared papaya fermentation product may be used in a form further including vegetable glycerin.
  • the papaya fermented product may be commercialized by mixing 94 to 96 parts by weight of the papaya fermentation product and 4 to 6 parts by weight of vegetable glycerin. The papaya fermented product prepared as described above was used in the following experiments.
  • mice were divided into 4 groups: normal (group 1), DNCB (group 2), papaya ferment (group 3), and DNCB + papaya ferment 100 ⁇ l (group 4).
  • group 1 normal
  • DNCB group 2
  • papaya ferment group 3
  • DNCB + papaya ferment 100 ⁇ l (group 4).
  • AD atopic dermatitis
  • 100 ⁇ l of 2% DNCB was repeatedly treated on the dorsal skin of a shaved mouse for 2 weeks using a 2 x 2 cm patch. After 3 weeks of AD induction, 100 ⁇ l of 2% DNCB was treated once more.
  • the papaya fermented product was fed for 2 weeks with DNCB treatment.
  • the papaya ferment was dissolved in drinking water and fed.
  • the overall experimental protocol is shown in FIG. 1.
  • the severity of clinical skin was defined as the sum of the scores given for each of the four symptoms, erythema/hemorrhage, edema, erosion, and dryness (0-3 points). , None; 1, weak; 2, moderate; 3, severe).
  • the observation results and clinical skin severity scores of the degree of atopic dermatitis improvement for each group are shown in FIGS. 2 and 3.
  • the spleen tissue was homogenized and dissolved. Protein concentration was measured using a Pierce® BCA protein assay kit (Thermo scientific, Rockford, IL 61101 USA). After loading 25 ⁇ g of protein into each well, and separating the protein using 10-15% SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) gel under 100-250V conditions for 1-2 hours, i-Blot (Life Technology , Carlsbad, CA) to the membrane for 7 minutes.
  • SDS-PAGE sodium dodecyl sulfate-polyacrylamide gel electrophoresis
  • the membrane was incubated with primary antibodies of I ⁇ B ⁇ and p65 NF- ⁇ B (Santa Cruz Biotech., Santa Cruz, CA) and then incubated with HRP ( horseradish peroxidase) conjugated secondary antibody (diluted 1:1000 in 5% skimmed milk solution) and incubated. After washing the membrane, the intensity of the protein band was quantified using ATTO CS image analyzer 3.0 (ATTO, Tokyo, Japan). As a control, GAPDH (Glyceraldehyde-3-phosphate Dehydrogenase) was used. The results are shown in FIG. 6.
  • Atopic dermatitis increases the IgE antibody response, which increases the activity of the IgE-dependent histamine vitreous body to promote histamine secretion, and histamine induces eosinophil infiltration and causes acute hypersensitivity reaction and itching.
  • serum IgE levels are known as an indicator of atopic dermatitis, and in particular, IgE is known to have a close correlation with clinical severity.
  • serum IgE and IgG levels are related to Th1 or Th2 immunity.
  • IgE and IgG levels in serum and spleen cells were measured. Serum IgE and IgG levels were significantly increased in the DNCB-treated group compared to the control group, whereas in spleen cells, the papaya fermented product-treated group significantly decreased IgE and IgG levels compared to the DNCB-treated group (Fig. 5).
  • the papaya fermented product according to the present invention can significantly reduce the amount of IgE and IgG secretion in the spleen cells, and thereby has an effect on inhibiting atopic dermatitis.
  • the DNCB-treated group had higher NF- ⁇ B and I ⁇ B ⁇ levels than the control group (p ⁇ 0.01), and the DNCB + papaya fermented product-treated group significantly decreased NF- ⁇ B and I ⁇ B ⁇ levels compared to the AD control group. It was confirmed (FIG. 6C). Activation of NF- ⁇ B and I ⁇ B ⁇ induces the expression of proinflammatory chemokine, and the results show that the papaya fermentation product according to the present invention can improve or treat atopic dermatitis by inhibiting the expression of proinflammatory chemokine. Confirmed.
  • the papaya fermentation product according to the present invention effectively reduces the number of skin lesions and mast cells, and significantly reduces the levels of NF- ⁇ B and I ⁇ B ⁇ in the cytoplasm involved in the expression of inflammatory genes. Confirmed through. In particular, it was confirmed that the papaya fermented product can effectively improve atopic dermatitis without cytotoxicity in vivo using a mouse model of atopic dermatitis. Therefore, the papaya fermented product according to the present invention can be usefully used in the development of pharmaceuticals, health functional foods, and cosmetics for the prevention, improvement or treatment of atopic dermatitis.
  • the above ingredients are mixed and filled in an airtight cloth to prepare a powder.
  • tablets are prepared by tableting according to a conventional tablet preparation method.
  • the above ingredients are mixed and filled into gelatin capsules to prepare a capsule.
  • 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. , To prepare granules, and can be used to prepare a health food composition 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.

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Abstract

La présente invention concerne une composition pharmaceutique pour prévenir ou traiter la dermatite atopique, et une composition quasi-médicamenteuse, une composition alimentaire ou une composition cosmétique pour prévenir ou soulager la dermatite atopique, toutes ces compositions contenant un produit de fermentation de Carica papaya Linn. Un produit de fermentation de Carica papaya Linn., selon la présente invention, utilise Carica papaya Linn., qui est un produit naturel, et présente de ce fait peu d'effets indésirables et diminue efficacement les lésions cutanées et le nombre de mastocytes, et diminue significativement les niveaux de NF-κB et IκBα intracytoplasmiques, lesquels sont impliqués dans l'expression de gènes pro-inflammatoires, et il est donc attendu que ce produit de fermentation puisse être efficacement utilisé dans le développement de produits pharmaceutiques, d'aliments fonctionnels de santé, de cosmétiques et similaires pour la prévention, le soulagement ou le traitement de la dermatite atopique.
PCT/KR2020/001739 2019-05-28 2020-02-07 Composition pharmaceutique pour la prévention ou le traitement de la dermatite atopique, contenant un produit de fermentation de carica papaya linn. Ceased WO2020242010A1 (fr)

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