WO2019103497A1 - Composition contenant un extrait naturel pour prévenir ou traiter le prurit - Google Patents

Composition contenant un extrait naturel pour prévenir ou traiter le prurit Download PDF

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WO2019103497A1
WO2019103497A1 PCT/KR2018/014471 KR2018014471W WO2019103497A1 WO 2019103497 A1 WO2019103497 A1 WO 2019103497A1 KR 2018014471 W KR2018014471 W KR 2018014471W WO 2019103497 A1 WO2019103497 A1 WO 2019103497A1
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extract
pruritus
present
extracts
leaf
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PCT/KR2018/014471
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English (en)
Korean (ko)
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김선영
손미원
배민정
이두석
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주식회사 바이로메드
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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 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)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • 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)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/538—Schizonepeta
    • 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)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present invention relates to a pharmaceutical composition for preventing or treating pruritus including (i) a sprout extract and (ii) a mold extract, a cotyledon extract, a non-leaf extract or a combination thereof, and a food composition for preventing or ameliorating pruritus.
  • Pruritus is a noticeable symptom of many skin conditions, and is an unpleasant sensation that causes the urge to scratch or rub the skin. Generally, this may occur irrespective of external stimuli, but may also be caused by mild mechanical contact with external substances, ambient temperature changes, chemical substances or electrical stimuli.
  • Skin diseases that cause pruritus include urticaria, eczematous skin diseases (such as atopic dermatitis), psoriasis, pemphigus, and dry skin.
  • Patients with chronic renal failure may present with pruritus and hemodialysis if they develop early itching, and the symptoms tend to be worse. Obstructive biliary disease, jaundice, acute erythropoiesis or Hotsky's disease Itching is well known to accompany.
  • the cause of the onset is not known, but the atrophy of the epidermis, the ovary and the sebaceous gland is observed, resulting in a decrease in the water content of the epidermis and a decrease in surface lipid It is known as the cause.
  • the quality of life is deteriorated due to the fever, pain and insomnia, but proper treatment is not performed because it does not accompany the symptoms of ordinary dermatitis through IgE such as erythema and chicken.
  • Therapeutic agents for pruritus developed so far include local or oral therapeutic agents such as moisturizers, topical steroids, anesthetics, antihistamines, antidepressants, and anti-opioid agents, as well as phototherapy using ultraviolet B and nerve stimulation.
  • these therapies have been reported to exhibit side effects such as insomnia, constipation, sleepiness, and elevation of prolactin. Therefore, it is urgently required to develop a new therapeutic agent for pruritus which is excellent in relieving or treating the pruritus even without side effects.
  • the present inventors have tried to develop a therapeutic agent for pruritus using a natural extract in order to improve the side effects of the existing pruritus.
  • the inventors of the present invention have found that a combination extract of Dulia, Brocoli, Liliaceae, and Non-foliar extracts is effective in the treatment or amelioration of pruritus.
  • the effect of the combined extract (mixed extract) And IL-6, IL-4, and IL-31 which are excellent and pruritus-inducing cytokines.
  • a pharmaceutical composition for preventing or treating pruritus comprising (i) quercetin extract and (ii) mold extract, apolipoprotein extract, non-leaf extract or a combination thereof.
  • Another object of the present invention is to provide a food composition for preventing or ameliorating pruritus, which comprises (i) quercetin extract and (ii) a mold extract, a self-leaf extract, a non-leaf extract or a combination thereof.
  • a pharmaceutical composition for preventing or treating pruritus comprising (i) quercetin extract and (ii) mold extract, apolipoprotein extract, non-leaf extract or a combination thereof.
  • filamentous plants include Actinidia arguta, A. colomikta, A. polygama, a combination thereof, or an inverted relative plant.
  • the fruit varieties include at least one selected from the group consisting of fruit, stem, stem vine, leaves and roots of a spruce tree.
  • Schizonepetae Spica is a flower stalk of Schizonepeta Tenuifolia Briquet, which is a plant of the Oriental herbaceous plant.
  • the mold is covered with soft hairs all over the ground, and the small flower of the fleshy pink in August ⁇ September starts to bloom from the lower part and it goes up.
  • his brother's temper is known to be innocent and sincere.
  • the main ingredient is d-menthone, dl-menthone and a small amount of d-limonene as essential oil components.
  • Perillae Folium is a leaf and end of Perilla frutescens Britton var. Acuta Kudo or Perilla frutescens Britton var. Crispa Decaisne, with a height of 30 to 60 cm And is called a proper place, a chopping machine and a folding chopper. It is produced in Korea, China, etc. and it is used for edible and medicinal purposes in Korea.
  • the lobulus is purple and has a unique flavor.
  • the stem is straight with a horny shape. Leaves are round or wedge-shaped with sawteeth at the edge. Flowers are purplish-colored and bloom in August ⁇ September, and shapes such as mouth and stem are similar to perilla.
  • the main ingredients are perilla aldehyde, d-limonene, ⁇ -pinene, cyanin, sterin, menthol, rosmarinic acid, (Kim and Hwang, 2006), it has been reported that ingestion of meat or fish prevents food poisoning and has strong antibacterial activity (Kim et al, 2000).
  • Eriobotryae Folium is a leaf of Eriobotrya japonica Lindley which is an evergreen tree belonging to Malaceae and contains nerolidol, farnesol, pinene, camphene, Myrcene, cymene, linalool amygdalin, ursolic acid, oleanolic aicd, malic acid, glucose, and the like. (1998)). In addition, it has been known that it is used for the treatment of cancer.
  • the spruce, foliage, baby leaf and non-leaf extract used in the present invention can be obtained by purchase or by direct extraction.
  • various extraction solvents such as polar solvents and nonpolar solvents can be used have.
  • Suitable polar solvents are (i) water, (ii) alcohols (preferably methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, 1-pentanol, Or ethylene glycol), (iii) acetic acid, (iv) dimethyl-formamide (DMFO) and (v) dimethylsulfoxide (DMSO).
  • alcohols preferably methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, 1-pentanol, Or ethylene glycol
  • acetic acid preferably methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, 1-pentanol, Or ethylene glycol
  • DMFO dimethyl-formamide
  • DMSO dimethylsulfoxide
  • Suitable nonpolar solvents are acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1- But are not limited to, pentane, 1-chlorobutane, 1-chloropentane, o-xylene, diisopropyl ether, 2- chloropropane, toluene, 1- chloropropane, chlorobenzene, benzene, diethyl ether, diethylsulfide, Methane, 1,2-dichloroethane, aniline, diethylamine, ether, carbon tetrachloride and THF (Tetrahydrofuran).
  • the amount of the solvent may be varied depending on the amount of the dwarf, mold, lobulus and non-lobule to be extracted, and is preferably 1 to 20 times the volume, more preferably 5 times, 15 times the volume. Most specifically 7 to 10 times the volume of the spider, horn, trilobal or non-lobular weights.
  • the extraction temperature of the extract of the present invention is not particularly limited and may be, for example, from 0 ° C to 120 ° C, and specifically from 20 ° C to 95 ° C.
  • the extraction time of the extract of the present invention is not particularly limited, and may be, for example, 1 hour to 10 days, specifically 1 hour to 6 hours, and more specifically 3 hours to 5 hours.
  • the extract of the present invention can be extracted by a known natural substance extraction method.
  • it can be extracted by cold extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction or heat extraction.
  • it can be extracted by hot water extraction or reflux cooling extraction method, and is extracted once to 10 times, more specifically, It can be repeatedly extracted seven times or seven times.
  • the extracts of Drosophila, Xanthomonas, Liliaceae and non-lobes used in the present invention can be extracted with water, C1 to C4 lower alcohols or a mixed solvent thereof.
  • the composition of the present invention may include extracts of spruce, foliage, japanese and non-leaf spirals using ethyl alcohol as a solvent.
  • the extracts of spruce, mold, lobulus and non-leaf lobes are injected into an extracting solvent of 6-10 times the volume (ml) of weight (g) It can be obtained by extracting at 70-95 ° C for 1-7 hours using a low-temperature extraction apparatus.
  • the extracts of Drosophila, Fusarium, Liliaceae and Non-foliage can be obtained by extracting Drosophila, Drosophila, Liliaceae and Non-foliage into extraction solvents respectively and extracting them at 80-95 ° C for 2-5 hours .
  • an example of a method for directly extracting the extracts of Drosophila, Drosophila, Trichophyton and Non-leaf lobes is as follows. 100 g of Agrobacterium tumefaciens, 100 g of molds, 100 g of cotyledon leaves and 100 g of non-foliar leaves were respectively added to 800 ml of 8 times distilled water and extracted at 85-95 ° C for 3 hours. After concentrating the extract at reduced pressure at 55-65 ° C, the concentrate was lyophilized to obtain extracts of spruce, chisel, lobular and non-leaf.
  • the extracts of Trichoderma sp., Trichoderma sp., Trichoderma lucifera, and Non-leaf lobes can be used in the form of a crude extract extracted with a solvent, and they can be purified and used in high purity.
  • the term " extract " means that it is used in the art as a crude extract as described above, but broadly includes fractions obtained by further fractionating the extract. That is, the extracts of Drosophila, Fusarium, Liliaceae and Non-foliage include not only those obtained by using the above-mentioned extraction solvent but also those obtained by additionally applying a purification process thereto.
  • the fractions obtained by the purification method are also included in the extracts of Trichoderma sp., Trichoderma sp.
  • the spruce, foliage, foliar and non-foliar extracts used in the present invention can be produced in powder form by an additional process such as vacuum distillation and freeze drying or spray drying.
  • the mixed extracts of Dawaya, Dahlia, Dahlia, Liliaceae, Dahlia and Non-leaf extracts used in the present invention can be prepared by mixing individual extracts of Dahlia, Dahlia, Liliaceae and Non-foliage, And may be prepared by treating the extractant in a state of mixing lobules, dahlia and non-foliage.
  • pruritus &quot includes any itching or pruritic condition, including an unpleasant sensation that causes a desire to scratch or rub the skin.
  • pruritus can be divided into pruritus due to skin disease and pruritus due to medical illness.
  • Pruritus due to skin diseases includes atopic dermatitis, urticaria, psoriasis, pemphigus, dry skin, lichen simplex chronicus, nodular swelling, and pruritus due to psoriasis.
  • pruritus due to medical diseases pruritus due to thyroid disease, pruritus due to hormonal abnormalities such as diabetes, chronic renal failure and renal pruritus or urinary poisoning due to hemodialysis, benign pruritus due to leukemia or lymphoma, Pruritus due to graft versus host disease, pruritus due to anemia and metabolic diseases, pruritus due to acquired immunodeficiency syndrome, and the like.
  • compositions of the present invention may be prepared with pharmaceutical compositions.
  • the composition of the present invention is a pharmaceutical composition
  • a pharmaceutical composition comprising (a) a pharmaceutical extract of the above-mentioned (i) Darwinian extract of the present invention and (ii) a mixed extract comprising a mold, a lobular, Effective amount; And (b) a pharmaceutically acceptable carrier.
  • the term " pharmaceutically effective amount " as used herein refers to an amount sufficient to achieve the therapeutic efficacy or preventive efficacy of pruritus of the above-mentioned (i) Galenic extract and (ii) a mixed extract comprising a mold lanceolate, a non-petiole extract, .
  • the present invention relates to a composition
  • a composition comprising extracts from natural plant materials such as a sprout, mold, leaflet and non-leaf, and has no adverse effects on the human body even when it is administered in an excessive amount. Therefore, the quantitative upper limit of the above- As shown in FIG.
  • the term " treatment " means reduction, suppression, sedation or eradication of pruritus, the target disease of the present invention.
  • the term " prevention " means any action that inhibits or delays the onset of pruritus, the target disease of the present invention, including therapeutic implications.
  • composition of the present invention can be used for prevention, improvement or treatment of pruritus, and can be used as a substitute for the treatment of pruritus.
  • the mixed extracts of progeny and apical lobules of the present invention not only express IL-6 in the above-mentioned mast cell line but also express IL-31, which is a cytokine in CD4 + T cells, which decreases IL-4 expression and is highly related to the onset of pruritus
  • IL-31 which is a cytokine in CD4 + T cells, which decreases IL-4 expression and is highly related to the onset of pruritus
  • the effect of the present invention is remarkably reduced.
  • the mixed extracts of progeny and spontaneous lobules of the present invention exhibit a remarkable effect of reducing cannabis in a rat model of pruritus induced by acetone.
  • the mixed extracts of aquatic and marine lobes of the present invention are distinguished in that they exhibit remarkably excellent effects as compared with the individual extracts of Dawai and Japanese lobules.
  • the mixing weight ratio of the extract (i) and the extract (ii) in the mixed extract comprising (i) the Galenic Extract and (ii) the Foliar Extract Can be from 20: 1 to 1:20, 15: 1 to 1:15, 10: 1 to 1:10, 9: 1 to 1: 9, 6: 1 to 1: 6, have.
  • the mixing weight ratio of the mixed extract is specifically 20: 1 to 1:15, 20: 1 to 1:10, 20: 1 to 1: 9, 20: 1 to 1: 6, 20: : 1 to 1: 1; More specifically 15: 1 to 1:15, 15: 1 to 1:10, 15: 1 to 1: 9, 15: 1 to 1: 6, 15: 1 to 1: 3, 15: One; Or 10: 1 to 1:10, 10: 1 to 1: 9, 10: 1 to 1: 6, 10: 1 to 1: 3, 10: 1 to 1:
  • &quot mixing weight ratio " in the present specification refers to a weight ratio (w / w) of each component or a weight ratio (w / w) of each extract before the extraction process.
  • the weight ratio of the individual extracts mixed to make the mixed extract is calculated.
  • the 'mixing weight ratio' means the weight ratio (w / w) of each component before the extraction process, the extraction process is calculated differently depending on whether the components are mixed or mixed. For example, when the complex extract of the present invention is prepared through a single extraction process that extracts a mixture of spiraea and japonica lobules with an extraction solvent, the 'mixing weight ratio' means that the single components of each of the spiraea and japonica lobules contained in the mixture Weight ratio.
  • the complex extract of the present invention is prepared by preparing each of the extracts of a single ingredient of a sprout and a lobular leaf and then mixing the extracts of the two ingredients, the 'mixing weight ratio' is a 'single component basis weight &Quot;
  • Single component basis weight weight of single component used to make single extract ⁇ (weight of single extract used to make final composite extract / weight of single extract prepared).
  • the pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier.
  • pharmaceutically acceptable carriers are those conventionally used in the field of manufacture and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, But are not limited to, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • the pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components.
  • a lubricant e.g., a talc, a kaolin, a kaolin, a kaolin, a kaolin, a kaolin, kaolin, kaolin, kaolin, sorbiol, sorbitol, etc.
  • Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).
  • the pharmaceutical composition of the present invention can be administered orally or parenterally.
  • parenteral administration intravenous administration, subcutaneous administration, subcutaneous administration, intramuscular administration, intranasal administration, intramuscular administration, intraperitoneal administration, Intraocular administration, and the like, and specifically, oral administration can be used.
  • the appropriate dosage of the pharmaceutical composition of the present invention varies depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate and responsiveness of the patient, Usually, a skilled physician can readily determine and prescribe dosages effective for the desired treatment or prophylaxis. According to a specific embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 0.001-1000 mg / kg.
  • the pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container.
  • the formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.
  • the pharmaceutical composition of the present invention may be administered in combination with a known compound or pharmaceutical composition having the effect of preventing or treating pruritus or pruritus-related symptoms.
  • a food composition for preventing or ameliorating pruritus comprising (i) quercetin extract and (ii) a mold extract, a self-leaf extract, a non-leaf extract or a combination thereof.
  • &quot improvement &quot
  • composition comprising (i) a quadriceps lulex extract of the present invention and (ii) a composition comprising a mold extract, a self-leaf extract, a non-leaf extract or a combination thereof is prepared as a food composition, And the like.
  • additional ingredients include, for example, proteins, carbohydrates, fats, nutrients, flavoring agents and flavoring agents.
  • Examples of the above-mentioned carbohydrates are monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol.
  • Natural flavorings such as tau martin and stevia extract (e.g., rebaudioside A and glycyrrhizin) and synthetic flavorings (saccharine, aspartame, etc.) can be used as flavorings.
  • the food composition of the present invention when prepared as a drink, it may further contain citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, juice, mulberry extract, jujube extract, licorice extract, have.
  • the food composition for preventing or ameliorating pruritus of the present invention is a composition for preventing or treating pruritus in the same manner as the above-mentioned " pharmaceutical composition for preventing or treating pruritus " Since common uses are made between the two inventions, the description thereof is omitted in order to avoid excessive redundancy in this specification.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising (i) a quadriceps laval extract of the present invention and (ii) a chrysanthemum extract, a lobule extract, a non-leaf extract or a combination thereof, And a method for preventing or treating pruritus.
  • administering or " administering " as used herein refers to the administration of a therapeutically effective amount of a composition of the present invention to a subject (subject) undergoing pruritus to form the same amount in the body of the subject.
  • a “therapeutally effective amount” of the composition means the amount of composition sufficient to provide a therapeutic or prophylactic effect to the subject to which the composition is to be administered, including a “ prophylactically effective amount ".
  • the term "subject” as used herein includes, without limitation, humans, mice, rats, guinea pigs, dogs, cats, horses, cows, pigs, monkeys, chimpanzees, baboons or rhesus monkeys . Specifically, the object of the present invention is human.
  • the method for preventing or treating the pruritus of the present invention is a method including a step of administering a pharmaceutical composition for preventing or treating pruritus, which is an embodiment of the present invention, so that the redundant contents are avoided from excessive complexity described in this specification To be omitted.
  • the present invention relates to a pharmaceutical composition for preventing or treating pruritus including (i) a prolapse extract and (ii) a mold extract, a cotyledon extract, a non-leaf extract or a combination thereof, and a food composition for preventing or ameliorating pruritus .
  • composition of the present invention is effective for the treatment or amelioration of pruritus.
  • it is more effective in treating pruritus than the individual extracts of spruce, , IL-6, IL-4 and IL-31.
  • FIG. 1 is a graph showing the inhibitory effects of IL-6 gene expression in mast cell (RBL-2H3) stimulated with A23187 in the treatment of the extracts of Dulia and its individual extracts and the mixed extract of Dulia and its varieties.
  • FIG. 2 is a graph comparing the inhibitory effects of IL-6 gene expression in mast cells (RBL-2H3) stimulated with A23187 in the treatment of the extracts of Dahlia and Liliaceae and the mixed extracts of Dahlia and Liliaceae.
  • FIG. 3 is a graph showing inhibitory effects of IL-6 gene expression in mast cells (RBL-2H3) stimulated with A23187 in the treatment of individual extracts of Dahlia and non-foliage and mixed extracts of Dahlia and non-foliage.
  • FIG. 4 is a graph comparing the inhibitory effects of the individual extracts of Mulberry and Mulberry leaf extracts on the production of IL-4 in mast cell (RBL-2H3) stimulated with A23187, and the mixed extract of Mulberry and Mulberry leaflets.
  • FIG. 5 is a graph comparing the inhibitory effects of the mixed extract and the mixed extracts of Mulberry and Mulberry leaf on the production of IL-4 in mast cell (RBL-2H3) stimulated with A23187.
  • FIG. 6 shows the inhibitory effects of the extracts of Dulia and Liliaceae on the production of IL-31 from P4 (Phorbol 12-myristate 13-acetate) and ionomycin-activated CD4 + T cells Fig.
  • FIG. 7 is a graph showing a comparison of the effect of reducing the feeling of lethargy in the treatment of the extracts of aquatic and common lobular extracts and the mixed extracts of aquatic and vernal leaflets in a rat model of pruritus induced by applying acetone to the skin.
  • % used to denote the concentration of a particular substance is intended to include solids / solids (wt / wt), solid / liquid (wt / The liquid / liquid is (vol / vol)%.
  • Actinidia arguta was purchased and used for the experiment. 100 g of Duckweed were added to 800 mL of distilled water, stirred well and then refluxed for 3 hours at 85 ⁇ 95 °C. The filtrate was concentrated under reduced pressure at 55 to 65 ° C and then lyophilized to obtain a herbal composition powdery flour at a yield of 35 to 40%.
  • Perillae Folium was purchased and used for the experiment. 100 g of the lobulus was added to 800 mL of distilled water and stirred well. The mixture was refluxed for 3 hours at an extraction temperature of 85-95 ° C., and the filtrate was separated. The filtrate was concentrated under reduced pressure at 55 to 65 ° C, and then lyophilized to obtain 25% to 30% of crude leaflets of crude drug composition.
  • Dried alfalfa ( Eriobotryae Folium ) Were purchased and used for the experiment. 100 g of nonpasted leaves were added to 800 mL of distilled water and stirred well. The mixture was refluxed for 3 hours at 85 ⁇ 95 °C and then the filtrate was separated. The filtrate was concentrated under reduced pressure at 55 to 65 ° C and freeze-dried to obtain non-fibrillated powdery herbal composition in a yield of 7 to 10%.
  • the wheat and the lobular leaves were mixed at a weight ratio (w / w) shown in Table 1 below, 8 times of distilled water was added thereto, After refluxing for 3 hours at the extraction temperature of ⁇ 95 °C, the filtrate was separated. The filtrate was concentrated under reduced pressure at 55 to 65 ° C, and then lyophilized to obtain a total of seven kinds of mixed extract powder of spruce and juliole.
  • Mast cells are well known as the pivotal cells for itching induction. It is known that interleukin-6 (IL-6, interleukin 6), secreted from mast cells and the like, is expressed in the peripheral nerve cell involved in itching and causes itching.
  • IL-6 interleukin-6
  • the inventors of the present invention examined the mast cell activity of the individual extracts of Drosophila, Drosophila, Liliaceae, and non-foliage of the present invention and the extracts of Drosophila, Drosophila, RBL-2H3 cells were used to stimulate cytokine (IL-6) after stimulation with calcium glass A23187.
  • mast cell RBL-2H3 cells were purchased from Korean Cell Line Bank.
  • RBL-2H3 cells were prepared in 24 well-plates at 2xlO < 5 > cells per well and stabilized for 6 hours.
  • all the media in the wells were removed, and then 0.2 ml of fresh medium was added to each of the extracts of Dahlia, Fusarium, Liliaceae, and non-foliage prepared in Preparation Examples 1 to 5 and mixed extracts of Dahlia, And treated with 0.25 ml at a concentration of 1 mg / ml.
  • the calcium glass A23187 was treated with 0.05 ml each to a final concentration of 1 ⁇ M.
  • each cell was harvested and RNA was isolated therefrom and the degree of expression of IL-6 was measured by RT-qPCR.
  • the rat IL-6 primer sequences used in the tests were as follows.
  • Figs. 1 to 3 The results are shown in Figs. 1 to 3. As shown in Figs. 1 to 3, when RBL-2H3 cells were treated with calcium glass A23187, IL-6 was highly expressed compared to the A23187 untreated group. However, the treatment of A23187 with the extracts of Dahlia, Chrysanthemum, Liliaceae and Non-Lobes of the present invention, and the mixed extracts of Dahlia and Dahlia, Dahlia and Liliaceae, Dahlia and Non-foliage, Respectively. In particular, it was confirmed that the effect of reducing the expression level of IL-6 was better in the experimental group treated with the mixed extract of Dalaa than each individual extract. Accordingly, it was confirmed that the mixed extracts of Drosophila and Drosophila, Drosophila, and Drosophila, Drosophila, and Non-foliage of the present invention are superior to the respective extracts in relieving pruritus.
  • Interleukin-4 Interleukin-4 (IL-4), secreted by mast cells, is expressed in neurons and is involved in the induction of chronic itching by such methods as increasing the responsiveness of nerve cells to pruritogens (Cell. 171 (1): 217-228, 2017; J.Cell.2017). Recently, it has been reported that the damage of skin barrier is closely related to cytokines such as IL-4, IL-13, IL-17 and IL-31. Especially, IL-31 is increased in hemodialysis patients with pruritus (Eur J Dermatol, 27 (3): 247-253, 2017; Br J Dermatol, 176 (2): 537-540, 2017).
  • the present inventors conducted the following experiments on RBL-2H3 cells in order to compare the inhibitory effect on the IL-4 expression by the mast cell activity of the extracts.
  • the RBL-2H3 Ker Cell Line Bank cell culture medium Minimum Essential Medium (Thermo Scientific Inc., USA) per well in a 24-well cell number 2x10 5 using a - Preparation and 6 in a 5% CO 2 incubator at 37 °C the plate Lt; / RTI > After removing the medium in the well, 0.2 ml of the fresh medium, and the Prana extract of Preparation Example 1, the Julliobacterium extract of Preparation Example 3 and the mixed extract of Prana and Primaifera of Preparation Example 6-1 were added to a final concentration of 1 mg / ml Were treated with 0.25 ml each (experimental group).
  • the calcium glass A23187 (Sigma Aldrich, USA) was treated with 0.05 ml each to a final concentration of 1 ⁇ M.
  • the normal group was not treated with any substance, and the negative control group was treated with only A23187.
  • the recovered IL-4 of the supernatant was measured using an ELISA kit (R & D systems Inc., USA) and expressed as a ratio of IL-4 expression to the induction group.
  • RBL-2H3 (Korean Cell Line Bank) cells were prepared in a 24-well plate at 2 ⁇ 10 5 cells per well using a Minimum Essential Medium medium (Thermo Scientific Inc., USA) and cultured in a 37 ° C. 5% Lt; / RTI > After the medium in the wells was completely removed, 0.2 ml of fresh medium and 0.25 ml of each of the mixed extracts of Preparation Example 6-1 to Preparation Example 6-7 were added to the final concentration of 1 mg / ml (Experimental group).
  • A23187 Sigma Aldrich, USA was treated with 0.05 ml each to a final concentration of 1 ⁇ M.
  • the normal group was not treated with any substance, and the negative control group was treated with only A23187.
  • the recovered IL-4 of the supernatant was measured using an ELISA kit (R & D systems Inc., USA) and expressed as a ratio of IL-4 expression to the induction group.
  • IL-4 was highly expressed compared to the A23187-untreated group.
  • the inhibition of IL-4 was found to be 57-65% in all extracts of mixed extracts of Dulia and Liliaceae at various mixing ratios.
  • Interleukin-31 (IL-31), which is mainly produced in Th2 lymphocytes, is a major pruritogen, which not only acts directly on neuronal receptors but also induces elongation and branching of neurons It has been reported to increase susceptibility to itch stimuli ( J Allergy Clin Immunol . 138 (2): 500-508, 2016).
  • the present inventors performed the following experiments to confirm the inhibitory effect of the above extracts on IL-31 produced from CD4 + T cells which are progenitors of Th2 lymphocytes.
  • CD4 + After removing the T cells with magnetic beads for CD4 + T Cell Isolation Kit (Miltenyi Biotec, Germany), using RPMI medium (Thermo Scientific Inc., USA) is fetal calf serum 10% was added per well 5x10 5 channels 96 well - plate.
  • Acetone is known to induce itching by inducing skin dryness and impaired skin barrier function ( J Clin Cosmet Dermatol 1 (3), 2017: doi http://dx.doi.org/10.16966/2576-2826.114.).
  • the inventors of the present invention found that the extracts of Preparation Example 1, Preparation Example 3, Preparation Example 6-1 and Preparation Example 6-4 were mixed at a mixing weight ratio of 1: 1 , 9: 1), the following experiment was conducted.
  • mice ICR, male, 7 weeks old
  • mice The extracts were orally administered at a dose of 200 mg / kg for 1 day / day for 10 days, respectively, from the start date, and the mice and the like were epilated one day before induction.
  • Negative control and experimental groups were induced by applying a cotton swab (2 cm x 2 cm) moistened with 2 ml of acetone (Sigma Aldrich, USA) to the hair removal site 3 days before the end of the day, and the normal group was applied with distilled water .
  • the video was taken for 30 minutes.
  • the number of scratches of the mouse was measured by calculating one continuous action of scratching the guiding area until the rear foot was lifted down to the floor.

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Abstract

La présente invention concerne une composition pharmaceutique pour prévenir ou traiter le prurit et une composition alimentaire pour prévenir ou soulager le prurit, où chacune des compositions comprend : (i) un extrait d'Actinidia arguta ; et (ii) un extrait de Schizonepeta tenuifolia, un extrait de Perilla ocymoides, un extrait de feuilles d'Eriobotrya japonica ou une combinaison de ceux-ci. Les compositions selon la présente invention ont pour effet de traiter ou de soulager le prurit, et notamment, comparativement à un extrait individuel d'Actinidia arguta, de Schizonepeta tenuifolia, de Perilla ocymoides, ou de feuille d'Eriobotrya japonica, un extrait constitué d'un mélange d'Actinidia arguta et des autres a un meilleur effet de traitement du prurit, et des effets de réduction de l'expression d'IL-6, IL-4, et IL-31, qui sont des cytokines provoquant un prurit.
PCT/KR2018/014471 2017-11-23 2018-11-22 Composition contenant un extrait naturel pour prévenir ou traiter le prurit WO2019103497A1 (fr)

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CN116096411A (zh) * 2020-09-01 2023-05-09 中外制药株式会社 含有作为活性成分的il-31拮抗剂的用于预防和/或治疗透析瘙痒的药物组合物
KR20240054710A (ko) 2022-10-19 2024-04-26 동국대학교 와이즈캠퍼스 산학협력단 자소엽 휘발성 향기 추출물을 유효성분으로 함유하는 우울증 및 불안장애의 개선 또는 치료용 조성물

Citations (5)

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JP2001206836A (ja) * 2000-01-27 2001-07-31 Kose Corp 皮膚外用剤
JP2003089658A (ja) * 2001-09-19 2003-03-28 Noevir Co Ltd 抗痒み効果に優れる皮膚外用剤並びに食品
JP2003231640A (ja) * 2002-02-04 2003-08-19 Unitika Ltd アトピー性皮膚炎治療剤
KR20040018118A (ko) * 2002-08-23 2004-03-02 주식회사 팬제노믹스 다래 추출물을 함유하는 알러지성 질환 및 비알러지성염증 질환의 치료 및 예방을 위한 약학 조성물
KR20100128979A (ko) * 2009-05-29 2010-12-08 김명옥 비파엽 추출물을 함유하는 아토피 피부염 예방 및 치료용 약제학적 조성물

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001206836A (ja) * 2000-01-27 2001-07-31 Kose Corp 皮膚外用剤
JP2003089658A (ja) * 2001-09-19 2003-03-28 Noevir Co Ltd 抗痒み効果に優れる皮膚外用剤並びに食品
JP2003231640A (ja) * 2002-02-04 2003-08-19 Unitika Ltd アトピー性皮膚炎治療剤
KR20040018118A (ko) * 2002-08-23 2004-03-02 주식회사 팬제노믹스 다래 추출물을 함유하는 알러지성 질환 및 비알러지성염증 질환의 치료 및 예방을 위한 약학 조성물
KR20100128979A (ko) * 2009-05-29 2010-12-08 김명옥 비파엽 추출물을 함유하는 아토피 피부염 예방 및 치료용 약제학적 조성물

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