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WO2022086127A1 - Composition destinée à prévenir ou traiter une affection abdominale inflammatoire comprenant un extrait de plantes médicinal complexe - Google Patents

Composition destinée à prévenir ou traiter une affection abdominale inflammatoire comprenant un extrait de plantes médicinal complexe Download PDF

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Publication number
WO2022086127A1
WO2022086127A1 PCT/KR2021/014596 KR2021014596W WO2022086127A1 WO 2022086127 A1 WO2022086127 A1 WO 2022086127A1 KR 2021014596 W KR2021014596 W KR 2021014596W WO 2022086127 A1 WO2022086127 A1 WO 2022086127A1
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WIPO (PCT)
Prior art keywords
inflammatory bowel
bowel disease
baekduong
herbal extract
hwangryeon
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English (en)
Korean (ko)
Inventor
이두석
이원우
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Helixmith Co Ltd
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Helixmith Co Ltd
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Publication of WO2022086127A1 publication Critical patent/WO2022086127A1/fr
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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K10/00Animal feeding-stuffs
    • A23K10/30Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/538Schizonepeta
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/71Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/71Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A61K36/718Coptis (goldthread)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00Function of food ingredients
    • A23V2200/30Foods, ingredients or supplements having a functional effect on health
    • A23V2200/324Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present invention is hwangryeon (Coptis Rhizome); Hyeonggae ( Schizonepeta tenuifolia Briquet); And it relates to a pharmaceutical composition for preventing or treating inflammatory bowel disease, comprising a complex herbal extract of Ecliptae Herba or Pulsatillae Radix as an active ingredient.
  • the present invention relates to a food composition or feed composition for preventing or improving inflammatory bowel disease comprising the complex herbal extract as an active ingredient.
  • Inflammatory bowel disease is a chronic intractable disease in which chronic inflammation or ulceration occurs in the mucous membranes of the large intestine and small intestine, causing diarrhea and bloody stools, and the symptoms temporarily improve and then recur.
  • inflammatory bowel disease is clinically similar, it is classified into two diseases, ulcerative colitis and Crohn's disease, which are different from each other in histological, endoscopic and immunological aspects.
  • Ulcerative colitis is a disease in which erosions or ulcers are continuously formed on the mucous membrane of the large intestine.
  • systemic symptoms such as Crohn's disease is a disease in which lesions such as ulcers occur discontinuously in any part of the digestive tract from the mouth to the anus. appears.
  • sulfasalazine an aminosalicylic acid product
  • side effects such as nausea, vomiting, anorexia, rash, headache, liver damage, leukopenia, abnormal red blood cells, proteinuria, and diarrhea.
  • strong side effects such as necrosis of the femoral head.
  • Infliximab a TNF- ⁇ monoclonal antibody, was used to treat Crohn's disease patients after it was approved by the US FDA as a treatment for Crohn's disease in 1998. is appearing Therefore, there is an urgent need to develop a new therapeutic agent for inflammatory bowel disease that is safe and has fewer side effects than the currently used inflammatory bowel disease treatment.
  • Coptis Rhizome is a herbaceous perennial plant of the Ranunculaceae family. ) ( Coptis chinensis Franchet), ) ( Coptis deltoidea CY Cheng et Hsiao) or Unryeon ( Coptis teeta Wallich), with the root removed. Yellow lily is detoxifying by detoxifying heat and heat, releasing heat and heat, and detoxification of fire. It belongs to ⁇ , and it is the removal of the fire and heat of the heart or stomach (four heart) and the removal of burnt things ( ⁇ ) at the same time. It is effective in regulating ( ⁇ ). Also, whole reading ( ), is known to be used for pathologies such as Changyang fever poison ( ⁇ ), and is known to have pharmacological effects such as antimicrobial action, blood pressure lowering action, and anti-inflammatory action.
  • Hyeonggae ( Schizonepeta tenuifolia Briquet) is an annual plant belonging to the Lamiaceae ( Labiatae ), and its above-ground part, Hyeonggae (Schizonepetae Herba) or the ear of flower (Schizonepetae Spica), is used medicinally.
  • Hyeonggae (Schizonepetae Herba) or the ear of flower (Schizonepetae Spica)
  • Chinese medicine it is used for symptoms of chills, fever, headache and sweating due to external sensitivities. It is used when there is fever and inflammation is spreading in the early stage of Changyang, and when it is roasted black, it has a hemostatic effect on hematemesis, discoloration, nosebleeds, urine bleeding, and uterine bleeding.
  • Herba is an annual herb of the Compositae family, and is an outpost of Eclipta prostrata Linne. It is also called Aejangcho, Mokhanryun, Mukducho, and Haryuncho. Hanryeoncho is known to have the effects of hemostasis, boeum, bosin, etc., and to strengthen muscles and bones.
  • Paekduong Pulsatillae Radix
  • Nogocho a dried root of a common root plant such as Pulsatilla koreana Nakai or Pulsatilla chinensis Regel, which is a perennial plant belonging to Ranunculaceae .
  • the inventors of the present invention showed that when using the complex herbal extracts of H.
  • the present invention was completed by finding an excellent therapeutic effect, particularly at a specific mixing ratio.
  • an object of the present invention is hwangryeon; brother-in-law; And to provide a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient.
  • Another object of the present invention is hwangryeon; brother-in-law; And to provide a food composition or feed composition for the prevention or improvement of inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient.
  • Another object of the present invention is hwangryeon; brother-in-law; And to provide a method for preventing, improving or treating inflammatory bowel disease, comprising administering to a subject a pharmaceutical composition or a food composition comprising a herbal extract of orchid or baekduong as an active ingredient.
  • Another object of the present invention is hwangryeon; brother-in-law; And it is to provide a use for preventing, improving or treating inflammatory bowel disease of the herbal extract of orchid or baekduong.
  • the inventors of the present invention showed that when using the complex herbal extracts of H. It is effective, and especially in a specific mixing ratio, an excellent therapeutic effect was found.
  • the present invention is hwangryeon; brother-in-law; And it provides a pharmaceutical composition, food composition or feed composition for the prevention, improvement or treatment of inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient, and a method for preventing, improving or treating inflammatory bowel disease using the same.
  • the present invention is hwangryeon; brother-in-law; And it provides a pharmaceutical composition for preventing or treating inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient.
  • the herbal extract is Hwangryeon; brother-in-law; And Hanryeoncho or Baekduong 1.5-15: 1: It may be a mixture in a weight ratio of 0.1-15.
  • the term "crude herbal extract” or “composite herbal extract” refers to an active ingredient of the pharmaceutical composition of the present invention, which includes extracts of Hwangryeon lily, Hyeonggae, Orchidaceae or Baekduong, or extracts extracted from each herbal mixture. it means.
  • “Coptis Rhizome” of the present invention refers to herbal medicines, which are perennial herbaceous plants of the Ranunculaceae , and Coptis japonica Makino, Chinese rhizome ( ) ( Coptis chinensis Franchet), ) ( Coptis deltoidea CY Cheng et Hsiao) or Unryeon ( Coptis teeta Wallich) refers to a rhizome from which the root has been removed.
  • Hyeonggae ( Schizonepeta tenuifolia Briquet) of the present invention means an annual plant belonging to the Lamiaceae ( Labiatae ), and its above-ground part, Hyeonggae (Schizonepetae Herba) or ear (flower stalk), Hyeonggae (Schizonepetae Spica) include
  • Ecliptae Herba of the present invention refers to an annual grass of the Compositae family, and is an outpost of Eclipta prostrata Linne, which is also referred to as Aejangcho, Moxa chrysanthemum, Mukducho, Haryeoncho, etc. .
  • “Baekduong (Pulsatillae Radix)” of the present invention is called Nogocho, and refers to the dried root of a coexisting plant such as Pulsatilla koreana Nakai or Pulsatilla chinensis Regel, which is a perennial plant belonging to Ranunculaceae . .
  • the extracts of Hwangryeon, Hyeonggae, Orchidaceae, and Baekduong extracts contained in the composition of the present invention are natural plant materials and have been used as food and folk medicine for a long time, the extract of the present invention extracted therefrom is also expected to have no problems such as toxicity and side effects. can do. Therefore, the extracts of Hwangryeon, Hyeonggae, Hanryeoncho, and Baekduong extract can be used in medicines, foods, feeds, and the like.
  • inflammatory bowel disease refers to a disease in which inflammation occurs in the intestines, that is, the small intestine and large intestine, and includes diseases in which abnormal chronic inflammation in the intestinal tract repeats improvement and recurrence. It also includes specific enteritis with known etiology, nonspecific enteritis of unknown cause, and enteritis resulting from other diseases, such as entero-Behcet's disease, and the like.
  • treatment refers to any action in which symptoms of inflammatory bowel disease are improved or cured by administration of the composition according to the present invention.
  • prevention refers to any action that suppresses or delays symptoms of inflammatory bowel disease by administration of the composition according to the present invention.
  • the term "comprising as an active ingredient” means including an amount sufficient to achieve the efficacy or activity of the extract of the present invention.
  • the pharmaceutical composition of the present invention may further include extracts of other herbal medicines known in the art to have the same or similar effects as those exhibited by the composition of the present invention.
  • the pharmaceutical composition of the present invention may further include an active ingredient known to have an inflammatory bowel disease treatment effect in the art. More specifically, the pharmaceutical composition is a glucocorticosteroid, such as steroids, sulfasalazine, mesalazine, such as 5-aminosalicylic acid (5-aminosalicylic acid, 5-ASA) drug, TNF It may further include one or more active ingredients selected from the group consisting of - ⁇ monoclonal antibodies.
  • the pharmaceutical composition of the present invention may further include an active ingredient that has an effect on diseases other than inflammatory bowel disease.
  • the herbal extract of the present invention When used together with an additional active ingredient, the herbal extract and the additional active ingredient may be administered simultaneously as one formulation, or may be administered simultaneously or sequentially as separate formulations.
  • the pharmaceutical composition of the present invention may be used alone or in combination with methods using surgery, hormone therapy, drug therapy, or a biological response modifier to treat inflammatory bowel disease.
  • the herbal extract used in the present invention can be obtained using a conventional extraction solvent known in the art.
  • a polar solvent or a non-polar solvent may be used.
  • the polar solvent includes water, a C 1 to C 6 alcohol (eg, methanol, ethanol, propanol, butanol, n-propanol, iso-propanol and n-butanol, etc.), acetic acid, or a mixture of the above polar solvents.
  • Non-polar solvents include acetone, acetonitrile, ethyl acetate, methyl acetate, butyl acetate, fluoroalkane, hexane, ether, chloroform, dichloromethane or mixtures of the above non-polar solvents.
  • the herbal extract is extracted with a solvent selected from the group consisting of water, C 1 to C 6 alcohol, acetic acid, and a mixed solvent thereof.
  • the herbal extract is extracted with 0.01 to 90% ethanol. More specifically, the herbal extract is 0.01 to 90%, 1 to 90%, 10 to 90%, 20 to 90%, 30 to 90%, 40 to 90%, 50 to 90%, 60 to 90%, 0.01 to Extracted with 80%, 1-80%, 10-80%, 20-80%, 30-80%, 40-80%, 50-80% ethanol. Most specifically, the herbal extract is extracted with 60 to 80% ethanol.
  • the herbal extract is extracted through hot water extraction, cold extraction, reflux cooling extraction, ultrasonic extraction, or a conventional extraction method known in the art.
  • extract has a meaning commonly used in the art as a crude extract, but broadly includes a fraction obtained by additionally fractionating the extract. That is, the herbal extract includes not only those obtained using the above-described solvent, but also those obtained by additionally applying a purification process thereto. For example, a fraction obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatographs (those prepared for separation according to size, charge, hydrophobicity or affinity), etc. The fraction obtained through the purification method is also included in the herbal extract of the present invention.
  • the pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier.
  • the pharmaceutically acceptable carriers are those commonly used in formulation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like.
  • the pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like, in addition to the above components.
  • a lubricant e.g., a talc, a kaolin, a kaolin, a kaolin, a kaolin, kaolin, kaolin, kaolin, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, a talct, a talct, a talct, a stevia, glycerin, glycerin, glycerin,
  • the pharmaceutical composition is a powder, granule, tablet, coated tablet, pill, dragee, capsule, liquid, suspension, gel, syrup, slurry, suppository, enema, emulsion, It may be formulated as pastes, ointments, creams, lotions, powders, sprays or suspensions.
  • the pharmaceutical composition is formulated as a solid preparation such as tablets, pills, powders, granules or capsules for oral administration or liquid preparations such as suspensions, internal solutions, emulsions or syrups.
  • the pharmaceutical composition may be formulated as a sterile aqueous solution, non-aqueous solution, suspension, emulsion, freeze-drying agent or suppository for parenteral administration.
  • the pharmaceutical composition may further include an appropriate carrier, excipient or diluent commonly used in the preparation of the pharmaceutical composition.
  • an appropriate carrier for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, mannitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil.
  • a suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration method, age, weight, sex, pathological condition, food, administration time, administration route, excretion rate and response sensitivity of the patient, An ordinarily skilled physician can readily determine and prescribe a dosage effective for the desired treatment or prophylaxis.
  • the daily dose of the pharmaceutical composition of the present invention is 1-100 mg/kg.
  • the inflammatory bowel disease is Crohn's disease, ulcerative colitis, enteric Behcet's disease, intestinal tuberculosis, hemorrhagic rectal ulcer, indeterminate colitis, bacterial enteritis, viral enteritis, amoebic enteritis and ischemic enteritis It may be a disease selected from the group consisting of colitis, but is not limited thereto.
  • the herbal extract is hwangryeon; brother-in-law; And Hanryeoncho is mixed in a weight ratio of 1.5-15: 1: 0.1-15. More specifically, the herbal extract is Hwangryeon; brother-in-law; and chrysanthemum 1.5-10: 1: 0.1-15, 1.5-7.5: 1: 0.1-15, 1.5-15: 1: 0.1-10, 1.5-10: 1: 0.1-10, 1.5-7.5: 1: 0.1 -10, 1.5-7 : 1 : 0.1-10, 1.5-5 : 1 : 0.1-10, 1.5-4 : 1 : 0.1-10, 1.5-3.5 : 1 : 0.1-10, 1.5-3 : 1 : 0.1 -10, 2-7 : 1 : 0.1-10, 2-5 : 1 : 0.1-10, 2-4 : 1 : 0.1-10, 2-3.5 : 1 : 0.1-10, 2-3 : 1 : 0.1 -10, 1.5-7.5 : 1 : 0.1-8, 1.5-7.5 : 1 :
  • the herbal extract is Hwangryeon; brother-in-law; And Hanryeonchoga 2-3: 1: weight ratio of 0.2-0.4, more specifically, the herbal extract is Hwangryeon; brother-in-law; And Hanryeoncho, when mixed in a weight ratio of 2.5: 1: 0.3 (15: 6: 2) shows the most excellent effect.
  • the herbal extract is hwangryeon; brother-in-law; And Baekduong 1.5-15: 1: It is mixed in a weight ratio of 0.1-15. More specifically, the herbal extract is Hwangryeon; brother-in-law; and Whitehead 1.5-15: 1: 0.1-10, 1.5-15: 1: 0.1-5, 1.5-15: 1: 0.1-2, 1.5-10: 1: 0.1-2, 1.5-9: 1: 0.1 -2, 1.5-7 : 1 :0.1-2, 1.5-5 : 1 : 0.1-2, 1.5-3 : 1 : 0.1-2, 2-10 : 1 : 0.1-2, 2-9 : 1 : 0.1 -2, 2-7: 1: 0.1-2, 2-5: 1: 0.1-2, 2-3: 1: 0.1-2, 1.5-15: 1: 0.1-1.5, 1.5-15: 1: 0.1 -1, 1.5-15: 1: 0.1-0.9, 1.5-15: 1: 0.1-0.7, 1.5-15: 1: 0.1-0.5, 1.5-15: 1: 0.1-0.3, 1.5-10: 1: 1:
  • the herbal extract is Hwangryeon; brother-in-law; And Baekduonggi 2-3: 1: 0.1-0.3 weight ratio, more specifically, the herbal extract is Hwangryeon; brother-in-law; And when Baekduong is mixed in a weight ratio of 2.5: 1: 0.2, the best effect is exhibited.
  • the present invention is hwangryeon; brother-in-law; And it provides a food composition for preventing or improving inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient.
  • the herbal extract is Hwangryeon; brother-in-law; And Hanryeoncho or Baekduong 1.5-15: 1: It may be a mixture in a weight ratio of 0.1-15.
  • the term “improvement” refers to any action of reducing a parameter related to a condition to be treated by administration of a composition comprising the extract of the present invention, for example, the severity of symptoms.
  • the food composition of the present invention may be prepared in the form of powder, granules, tablets, capsules or beverages.
  • various foods such as candy, drinks, gum, tea, vitamin complexes, or health supplements.
  • the food composition of the present invention includes health functional food and health food.
  • the food composition of the present invention can be taken for a long time.
  • the food composition of the present invention may include components commonly added during food production, for example, proteins, carbohydrates, fats, nutrients, seasonings and flavoring agents.
  • examples of the above-mentioned carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose, oligosaccharides and the like; and polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • flavoring agents natural flavoring agents [taumatine, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used.
  • citric acid, high fructose, sugar, glucose, acetic acid, malic acid, fruit juice, licorice root extract, jujube extract, licorice extract, etc. may include
  • the present invention is hwangryeon; brother-in-law; And it provides a feed composition for preventing or improving inflammatory bowel disease comprising a herbal extract of orchid or baekduong as an active ingredient.
  • the herbal extract is Hwangryeon; brother-in-law; And Hanryeoncho or Baekduong 1.5-15: 1: It may be a mixture in a weight ratio of 0.1-15.
  • the pharmaceutical composition comprising the mixed herbal extract of the present invention as an active ingredient exhibits excellent therapeutic effects in inflammatory bowel disease, particularly Crohn's disease or ulcerative colitis, and can be used as a novel therapeutic agent.
  • the pharmaceutical composition of the present invention can be used as a safe therapeutic agent by reducing the side effects of existing therapeutic agents by including a natural product as an active ingredient.
  • % used to indicate the concentration of a specific substance is (weight/weight) % for solid/solid, (weight/volume) % for solid/liquid, and Liquid/liquid is (volume/volume) %.
  • the efficacy of the mixed herbal extract on inflammatory bowel disease, in particular, ulcerative colitis was confirmed.
  • the DSS-induced inflammatory bowel disease model is known to exhibit morphological changes and symptoms similar to those of human ulcerative colitis. Accordingly, after 8-week-old male mice (C57BL/6) were acclimatized for more than a week, Dextran Sulfate Sodium (DSS; 36,000-50,000 MW, MP Biomedicals, USA) was administered to induce ulcerative colitis.
  • DSS Dextran Sulfate Sodium
  • control group group administered with DSS and distilled water
  • Bowel disease is usually evaluated through clinical symptoms such as weight loss, diarrhea, and bloody stools.
  • the disease activity index is a method of analyzing the degree of intestinal disease by measuring weight loss rate, stool condition, and bleeding and assigning a score to each.
  • the normal group, the control group, and the experimental group were compared by analyzing the DAI by measuring the weight loss rate, stool status, and bleeding.
  • the DSS feeding method of the control group and the experimental group was prepared by diluting DSS in negative water to 2.5%, then feeding 100 mL of the DSS to the mice and replacing them every 2 days, DSS was fed for a total of 5 days.
  • mice in each group was measured and calculated as the weight loss rate, and the condition of stool and the presence or absence of bloody stool were checked.
  • scores were calculated according to the criteria in Table 2 below.
  • the normal group was orally administered 0.4 mL of distilled water once/day for 10 days from the start of the experiment.
  • the experimental group was administered 50 mg/kg of the single and mixed herbal extracts prepared in Preparation Example, and was orally administered once/day for 10 days from the start date of the experiment.
  • DAI Disease Activity Index
  • the normal group was orally administered 0.4 mL of distilled water once/day for 10 days from the start of the experiment.
  • the experimental group was administered 50 mg/kg of the single and mixed herbal extracts prepared in Preparation Example, and was orally administered once/day for 10 days from the start date of the experiment.
  • DAI Disease Activity Index
  • the mixed herbal extract group of Hwangryeon, Hyeonggae and Baekduong of the present invention has a lower DAI value and less weight change compared to the (negative) control group and the single herbal extract group (Comparative Examples 1, 2 and 4). was shown.
  • RAW264.7 cells were cultured in RPMI medium (Corning, USA) containing fetal bovine serum (Fetal Bovine Serum, FBS, Gibco TM , USA) and antibiotics (1% Penicillin, Streptomycin [P/S] Gibco-BRL, USA). cultured under Specifically, the incubator was maintained at a temperature of 37° C., and a gas mixed with 95% air and 5% CO 2 was continuously supplied so that appropriate conditions for cell culture were prepared. Cells were cultured 24 hours before the experiment so as to become 5x10 4 cells/well in a 24-well plate.
  • the (negative) control group and the LPS-treated group were pretreated with the cell culture solution for one hour after removing the supernatant of the prepared 24-well plate.
  • the experimental group was pre-treated with the single and complex herbal extracts prepared in Preparation Example for one hour.
  • each of the extracts was pretreated at a concentration of 10 ⁇ g/ml
  • each of the extracts was pretreated at a concentration of 20 ⁇ g/ml.
  • the (negative) control group was treated with the cell culture solution, and the LPS-treated group and the experimental group were treated with LPS at a concentration of 100 ng/ml for 24 hours. Thereafter, the supernatant was taken and the change in the nitric oxide content was evaluated by measuring the absorbance at 520 and 550 nm wavelength values through the Griess assay kit (G2930, Promega, USA). It was measured twice in the same way, and the results are shown in Table 5.
  • the mixed herbal extract group of Hwangryeon, Hyeonggae, and Orchid liana of the present invention exhibited lower NO-producing ability compared to the LPS-treated group and the single herbal extract group (Comparative Examples 1 to 3).
  • the (negative) control group and the LPS-treated group were pretreated with the cell culture solution for one hour after removing the supernatant of the prepared 24-well plate.
  • the experimental group was pre-treated with the single and complex herbal extracts prepared in Preparation Example for one hour.
  • the extracts were pretreated at a concentration of 10 ⁇ g/ml, respectively, and in the third (3 rd ) experiment, the extracts were pretreated at a concentration of 20 ⁇ g/ml, respectively.
  • the (negative) control group was treated with the cell culture solution, and the LPS-treated group and the experimental group were treated with LPS at a concentration of 100 ng/ml for 24 hours. Thereafter, the supernatant was taken and the change in the nitric oxide content was evaluated by measuring the absorbance at 520 and 550 nm wavelength values through the Griess assay kit (G2930, Promega, USA). It was measured three times in the same way, and the results are shown in Table 6.
  • the above ingredients are mixed and filled in an airtight bag to prepare a powder.
  • tablets are prepared by tableting according to a conventional tablet manufacturing method.
  • the above ingredients are mixed and filled in a gelatin capsule to prepare a capsule.
  • each component is added to purified water to dissolve it, an appropriate amount of lemon flavor is added, the above components are mixed, purified water is added, and purified water is added to the total amount to be adjusted to 100 ml, and then filled in a brown bottle. Sterilize to prepare a solution.
  • Vitamin B6 0.5 mg
  • composition ratio of the above vitamin and mineral mixture is a composition that is relatively suitable for health food in a preferred embodiment, but the mixing ratio may be arbitrarily modified. , to prepare granules, and can be used for preparing health food compositions according to a conventional method.
  • the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized, then refrigerated. It is used to prepare the health drink composition of the invention.
  • composition ratio is prepared by mixing ingredients suitable for relatively favorite beverages in a preferred embodiment, the mixing ratio may be arbitrarily modified according to regional and national preferences such as demand class, demanding country, and use.
  • the present invention is hwangryeon (Coptis Rhizome); Hyeonggae ( Schizonepeta tenuifolia Briquet); And it relates to a pharmaceutical composition for preventing or treating inflammatory bowel disease, comprising a complex herbal extract of Ecliptae Herba or Pulsatillae Radix as an active ingredient.
  • the present invention relates to a food composition or feed composition for preventing or improving inflammatory bowel disease comprising the complex herbal extract as an active ingredient.

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Abstract

La présente invention concerne une composition pharmaceutique pour prévenir ou traiter une affection abdominale inflammatoire, contenant, en tant que principes actifs, des extraits de plantes médicinaux de rhizome de Coptis, de Schizonepeta tenuifolia et d'herbe d'Ecliptae ou de racine de Pulsatillae. De plus, la présente invention concerne une composition d'aliment pour l'homme ou une composition d'aliment pour animaux pour la prévention ou l'atténuation d'une affection abdominale inflammatoire, comprenant l'extrait de plante médicinal en tant que principe actif.
PCT/KR2021/014596 2020-10-21 2021-10-19 Composition destinée à prévenir ou traiter une affection abdominale inflammatoire comprenant un extrait de plantes médicinal complexe Ceased WO2022086127A1 (fr)

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