WO2021071269A1 - Composition for preventing or treating inflammatory bowel disease comprising extracts of complex herbal medicines - Google Patents

Composition for preventing or treating inflammatory bowel disease comprising extracts of complex herbal medicines Download PDF

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WO2021071269A1
WO2021071269A1 PCT/KR2020/013713 KR2020013713W WO2021071269A1 WO 2021071269 A1 WO2021071269 A1 WO 2021071269A1 KR 2020013713 W KR2020013713 W KR 2020013713W WO 2021071269 A1 WO2021071269 A1 WO 2021071269A1
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inflammatory bowel
bowel disease
extract
pharmaceutical composition
group
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PCT/KR2020/013713
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French (fr)
Korean (ko)
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이원우
이두석
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주식회사 헬릭스미스
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Publication of WO2021071269A1 publication Critical patent/WO2021071269A1/en

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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)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A61K36/718—Coptis (goldthread)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • 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)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • 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
    • A23V2200/32—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the digestive tract
    • 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
    • A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
    • 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 is Coptis; Brotherhood; And it provides a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease, comprising a complex herbal extract of nasturtium or baekduong 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, resulting in diarrhea and bloody stools, temporarily improving symptoms, and recurring.
  • Inflammatory bowel disease is clinically similar, but classified into two diseases, ulcerative colitis and Crohn's disease, which are different in histological findings, endoscopy and immunological aspects.
  • Ulcerative colitis is a disease in which soreness (erosion) or ulcers are continuously formed on the mucous membrane of the large intestine. Symptoms are limited only in the large intestine. Bloody stools, mucous stools, diarrhea, and abdominal pain occur. In severe cases, fever, weight loss, and anemia.
  • 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.In addition to abdominal pain, diarrhea, and bloody stools, symptoms such as fever, weight loss, systemic malaise, and anemia in severe cases. Appears. The exact etiology of such inflammatory bowel disease has not been fully identified, but it is estimated that activation of inflammatory mediators and immune cells are important pathogens due to autoimmune diseases, along with environmental or genetic factors. Persistent and inappropriate activation of the intestinal immune system leads to chronic mucositis inflammation, especially mucosal destruction and ulcers by infiltration of neutrophils, macrophages, lymphocytes and mast cells.
  • sulfasalazine an aminosalicylic acid
  • side effects such as nausea, vomiting, loss of appetite, rash, headache, liver injury, leukocytosis, abnormal red blood cells, proteinuria, and diarrhea. Strong side effects, such as necrosis of the femoral head, have been reported.
  • Infliximab a TNF- ⁇ monoclonal antibody, was used to treat Crohn's disease patients after being 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 safer and has fewer side effects than the currently used inflammatory bowel disease treatments.
  • Coptis Rhizome is a medicinal herb that is a perennial herbaceous plant of the Ranunculaceae family. The roots are removed as the rootstock. Hwangryeon is to cool heat and dry moisture, detoxification while releasing heat and heat. Self-centeredness, which belongs to the ⁇ ), which removes the burning heat of the heart or stomach (self-heartedness) and at the same time removes the ones that have been dying ( ⁇ ). It is effective in Jebeon ( ⁇ ).
  • methods for use in diseases such as ontoxication and changyang fever are known, and are 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 family (Labiatae), and its above-ground part, Hyeonggae (Schizonepetae Herba) or the ear of flowers (Schizonepetae Spica), is used for medicinal purposes.
  • Hyeonggae (Schizonepetae Herba) or the ear of flowers (Schizonepetae Spica)
  • oriental medicine it is used for the symptoms of chills, fever, headache and sweating due to external sensitivity.
  • a woman has convulsions and seizures due to a cold after childbirth, it is taken as a single powder and is effective for skin itching. It is used when there is a fever and inflammation spreads in the early stage of the window candle, and if it is roasted black, it has a hemostatic effect on hematopoiesis, bleeding, nosebleeds, urine bleeding and uterine bleeding.
  • Hanryeoncho (Ecliptae Herba) is a perennial plant of the Asteraceae (Compositae), and is an outpost of the Hanryeoncho (Eclipta prostrata Linne). It is also called aejangcho, mokhannyeon, mukducho, and hayeoncho. Hanryeoncho has the effect of hemostasis, boeum ( ⁇ ) and boshin ( ⁇ ), and is known to strengthen muscles and bones.
  • Baek Duong Pulsatillae Radix
  • Nogocho is a perennial plant belonging to the Ranunculaceae family, such as Pulsatilla koreana Nakai or Baek Duong (Pulsatilla chinensis Regel).
  • Amoeba protozoa and Eumdo protozoa inhibitory effect, cardiac toxicity, soothing, analgesic effect, and skin mucosa stimulating effect have been reported.
  • the present inventors performed better treatment than using each single extract when using complex herbal extracts of Hwangryeon, Hyeonggae, Hanryeoncho, and Baekduong. Having found that there is an effect, the present invention was completed.
  • the object of the present invention is Cwangryun; Brotherhood; And it is to provide a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease comprising the herbal extract of nasturtium or baekduong as an active ingredient.
  • Another object of the present invention is Hwangnyeon; Brotherhood; And it is to provide a food composition or feed composition for preventing or improving inflammatory bowel disease, comprising the herbal extract of nasturtium or baekduong as an active ingredient.
  • Another object of the present invention is Hwangnyeon; Brotherhood; And it is 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 nasturtium or baekduong as an active ingredient.
  • the present invention is Coptis; Brotherhood; And it provides a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease comprising the herbal extract of nasturtium or baekduong as an active ingredient.
  • the term "herbal extract” or “combined herbal extract” is an active ingredient of the pharmaceutical composition of the present invention, including each of Coptis chinensis, Hyeonggae, Hanryeoncho or Baekduong extract, or including extracts extracted from each herbal mixture it means.
  • Coptis Rhizome of the present invention means a herbaceous perennial herbaceous plant of Ranunculaceae, Coptis japonica Makino, Coptis chinensis Franchet, Triangular Leaf Coptis deltoidea CY Cheng et Hsiao or Woonryeon ( ⁇ ) It is the rootstock of Coptis teeta Wallich and refers to the root removed.
  • Hyunggae (Schizonepeta tenuifolia Briquet) of the present invention means an annual vegetation belonging to the Lamiaceae family (Labiatae), and includes Hyeonggae (Schizonepetae Herba) or the ear of flowers (Schizonepetae Spica), which is the above-ground part thereof do.
  • Ecliptae Herba of the present invention refers to the annual herb of the chrysanthemum family (Compositae), and refers to what is also called aejangcho, mokhanryeon, mukducho, haliancho, etc. .
  • “Baek Duong (Pulsatillae Radix)” of the present invention is called Nogocho, and refers to the drying of the roots of plants of the same genus such as Pulsatilla koreana Nakai or Pulsatilla chinensis Regel, a perennial plant belonging to Ranunculaceae. .
  • inflammatory bowel disease refers to a disease in which inflammation occurs in the intestine, ie, small intestine, large intestine, etc., and includes a disease in which abnormal chronic inflammation in the intestine repeats improvement and recurrence. In addition, it includes specific enteritis of which the cause has been identified, non-specific enteritis of which the cause is not known, and enteritis caused by other diseases, for example, enteric Behcet's disease, and the like.
  • treatment refers to all actions 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 "including 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 an extract of another herbal medicine known in the art to have the same or similar effect as that of the composition of the present invention.
  • the pharmaceutical composition of the present invention may further contain an active ingredient known to have an effect on treating inflammatory bowel disease in the art. More specifically, the pharmaceutical composition includes steroids such as glucocorticosteroids, 5-aminosalicylic acid (5-ASA) drugs such as sulfasalazine and mesalazine, and TNF - ⁇ may further contain one or more active ingredients selected from the group consisting of monoclonal antibodies.
  • steroids such as glucocorticosteroids
  • 5-aminosalicylic acid (5-ASA) drugs such as sulfasalazine and mesalazine
  • TNF - ⁇ may further contain 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 showing 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 surgery, hormone therapy, drug therapy, or methods of using 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.
  • Polar solvents include water, C1 to C6 alcohols (eg, methanol, ethanol, propanol, butanol, normal-propanol, iso-propanol and normal-butanol, etc.), acetic acid, or a mixture of the 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, C1 to C6 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 It is extracted with 80%, 1 to 80%, 10 to 80%, 20 to 80%, 30 to 80%, 40 to 80%, 50 to 80% ethanol. Most specifically, the herbal extract is extracted with 60 to 80% ethanol.
  • the herbal extract is extracted through hot water extraction, cold needle extraction, reflux cooling extraction, ultrasonic extraction, or conventional extraction methods known in the art.
  • extract has a meaning commonly used as a crude extract in the art, but also includes a fraction obtained by further fractionating the extract in a broad sense. That is, the herbal extract includes not only those obtained by using the above-described solvent, but also those obtained by additionally applying a purification process thereto. For example, fractions obtained by passing the extract through an ultrafiltration membrane having a certain molecular weight cut-off value, separation by various chromatographs (made for different separation in size, charge, hydrophobicity or affinity), etc. Fractions obtained through the purification method are also included in the herbal extract of the present invention.
  • the pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier.
  • the pharmaceutically acceptable carrier is commonly used in the formulation, lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, and the like, but are not limited thereto.
  • 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, a kaolin, kaolin, kaolin, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, a talct, a talct, a talct, a stea, stevia, glycerin, glycerin, glycerin, g
  • the inflammatory bowel disease is Crohn's disease, ulcerative colitis, long Behcet's disease, intestinal tuberculosis, hemorrhagic rectal ulcer, indeterminate colitis, bacterial enteritis, viral enteritis, amoebic enteritis and ischemic It is a disease selected from the group consisting of colitis.
  • the pharmaceutical composition is powder, granule, tablet, coated tablet, pill, dragee, capsule, liquid, suspension, gel, syrup, slurry, suppository, enema, emulsion, It can be formulated as pastes, ointments, creams, lotions, powders, sprays or suspensions.
  • the pharmaceutical composition may be formulated as a solid preparation such as a tablet, a pill, a powder, a granule or a capsule, or a suspension, a liquid solution, an emulsion, or a syrup for oral administration.
  • the pharmaceutical composition may be formulated as a sterilized aqueous solution, a non-aqueous solution, a suspension, an emulsion, a lyophilized agent, or a suppository for parenteral administration.
  • the pharmaceutical composition may further include an appropriate carrier, excipient, or diluent commonly used in the manufacture of pharmaceutical compositions.
  • an appropriate carrier for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, mannitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl Pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil.
  • the herbal extract is Hwangnyeon; Brotherhood; And nasturtium or baekduongi are mixed in a weight ratio of 0.05-20: 0.05-20: 0.05-20. More specifically, the herbal extract is Hwangryeon; Brotherhood; And nasturtium or baekduongi 1-10: 1-10: 1-10, 1: 1-10: 1-10, 1-10: 1: 1-10, 1-10: 1-10: 1, 3: 1 -10: 1-10, 1-10: 3: 1-10, 1-10: 1-10: 3, 10: 1-10: 1-10, 1-10: 10: 1-10, 1-10 : 1-10: 10, 1: 1: 1-10, 3: 1: 1-10, 10: 1: 1-10, 1: 3: 1-10, 10: 1: 1-10, 3: 3 : 1-10, 3:10: 1-10, 10:10: 1-10 It is mixed in a weight ratio.
  • the herbal extract is Hwangnyeon; Brotherhood; And nasturtium or baekduongi 10:1: 1-10 is mixed in a weight ratio.
  • the herbal extract is Coptis Coptis; Brotherhood; And when nakryeoncho or baekduong is mixed in a weight ratio of 10:1:1, 10:1:3, and 10:1:10, the effect is excellent.
  • a suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, mode of administration, age, weight, sex, pathological condition, food, administration time, route of administration, excretion rate and response sensitivity of the patient, Usually the skilled practitioner can readily determine and prescribe a dosage effective for the desired treatment or prophylaxis.
  • the daily dosage of the pharmaceutical composition of the present invention is 1-100 mg/kg.
  • the present invention is Coptis; Brotherhood; And it provides a food composition for preventing or improving inflammatory bowel disease, comprising the herbal extract of nasturtium or baekduong as an active ingredient.
  • the term "improvement” refers to all actions of reducing the severity of a parameter, for example, symptoms related to a condition to be treated by administration of a composition comprising an extract of the present invention.
  • 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, beverages, gum, tea, vitamin complexes, or health supplement foods.
  • the food composition of the present invention includes health functional foods and health foods.
  • the food composition of the present invention can be taken for a long time.
  • the food composition of the present invention may include ingredients that are commonly added during food production, and include, for example, proteins, carbohydrates, fats, nutrients, flavoring agents, and flavoring agents.
  • examples of the aforementioned carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • flavoring agents natural flavoring agents [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.]) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used.
  • citric acid liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, cephalic extract, jujube extract, licorice extract, etc.
  • the present invention is Coptis; Brotherhood; And it provides a feed composition for preventing or improving inflammatory bowel disease, comprising the herbal extract of nasturtium or baekduong as an active ingredient.
  • the extracts of Coptis Rhizoma, Hyeonggae, Hanryeoncho, and Baekduong contained in the composition of the present invention are natural plant materials, and have been used as edible and folk medicine for a long time, so it is expected that the extract of the present invention extracted from them will also have no problems such as toxicity and side effects. I can. Therefore, the extracts of Coptisaceae, Hyeonggae, Hanryeoncho, and Baekduong can be used as pharmaceuticals, food compositions, and feed compositions.
  • the contents of the extract of Coptis chinensis, Hyeonggae, Hanryeoncho, and Baekduong contained in the food composition and feed composition of the present invention are the same as the contents of the extraction of the mixed extract contained in the pharmaceutical composition, the contents in common between the two are In order to avoid excessive complexity of the present specification, description thereof is omitted.
  • the present invention includes the above-described present Coptis Coptis; Brotherhood; And it provides a method for preventing, improving or treating inflammatory bowel disease comprising administering to a subject a pharmaceutical composition or a food composition comprising a mixed extract of nasturtium or baekduong as an active ingredient.
  • administering refers to a subject by directly administering a therapeutically or prophylactically effective amount of a composition of the present invention to a subject (individual) suffering from or likely to suffer from the subject disease. It means to ensure that the same amount is formed in the body.
  • the administration route of the composition of the present invention may be administered orally or parenterally through any general route as long as it can reach the target tissue.
  • the composition of the present invention may be administered using any device capable of delivering the active ingredient to target cells, tissues or organs.
  • the "therapeutically effective amount” of the composition means an amount of the composition sufficient to provide a therapeutic or prophylactic effect to a subject to which the composition is to be administered, and is meant to include a “prophylactically effective amount”.
  • the subject is selected from the group consisting of humans, monkeys, cows, horses, sheep, pigs, chickens, turkeys, quails, cats, dogs, mice, rats, rabbits, and guinea pigs. It is not limited. More specifically, the subject is a human.
  • Inflammatory bowel disease which is the target disease of the prevention and method of the present invention, is the same as defined in relation to the target disease of the pharmaceutical composition or food composition.
  • the method for preventing or treating inflammatory bowel disease of the present invention is a method comprising administering a pharmaceutical composition, which is an aspect of the present invention, excessive redundancy in the present specification for overlapping contents with respect to the pharmaceutical composition The description is omitted in order to avoid.
  • the pharmaceutical composition comprising the mixed herbal extract of the present invention as an active ingredient exhibits excellent therapeutic effect in inflammatory bowel disease, particularly Crohn's disease or ulcerative colitis, and can be used as a novel therapeutic agent.
  • composition of the present invention can be used as a safe therapeutic agent to reduce side effects of existing therapeutic agents by including a natural product as an active ingredient.
  • 1 shows the DAI value of each administration group measured in the DSS-induced inflammatory bowel disease model.
  • Figure 2 shows the length of the colon of each administration group measured in the DSS-induced inflammatory bowel disease model.
  • Figure 3 shows the survival rate of each administration group measured in the DNBS-induced inflammatory bowel disease model.
  • Figure 4 shows the DAI value of each administration group measured in the DNBS-induced inflammatory bowel disease model.
  • FIG. 6 shows the DAI values of each administration group measured in the DSS-induced inflammatory bowel disease model.
  • % used to indicate the concentration of a specific substance is (weight/weight)% for solids/solids, (weight/volume)% for solids/liquids, and Liquid/liquid is (vol/vol) %.
  • the efficacy of the mixed herbal extract on inflammatory bowel disease 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, 8-week-old male mice (C57BL/6) were acclimated and bred for more than a week, and then Dextran Sulfate Sodium (DSS; 36,000-50,000 MW, MP Biomedicals, USA) was administered to induce ulcerative colitis.
  • the normal group without any treatment the DSS and distilled water administration group (negative control), the DSS and 5-Aminosalicylic Acid (5-ASA; Tokyo Chemical Industry Co., Japan) administration group (positive control), and DSS and each mixed herbal extract (The experiment was conducted by classifying it into the group (experimental group) administered with Hwangryeon, Hyeonggae, Baekduong, and Hanryeoncho).
  • DAI Disease Activity Index
  • the weight loss rate, stool condition, and bleeding were measured and DAI was analyzed to compare the normal group, the control group, and the experimental group.
  • the positive control group was orally administered 5-ASA diluted in negative water at a dose of 25 mg/kg once/day for 14 days from the start of the experiment.
  • each herbal extract prepared in Preparation Example was mixed and administered at the dose (mg/kg) shown in Table 2, and oral administration was performed once/day for 14 days from the start of the experiment.
  • DAI Disease Activity Index
  • the inflammatory response in bowel disease can be assessed to the extent that the length of the large intestine is reduced. Accordingly, in this example, the length of the large intestine was measured to compare the normal group, the control group, and the experimental group.
  • mice classified into the administration group as shown in Table 3 were sacrificed with carbon dioxide gas, and then the colon part was removed.
  • the length of the large intestine was measured from the removed large intestine, and the results are shown in Table 3 and FIG. 2 below.
  • the efficacy of the mixed herbal extract on inflammatory bowel disease was confirmed.
  • the DNBS-induced inflammatory bowel disease model is known to be closely related to Crohn's disease in humans in that it induces a T cell-mediated immune response. Accordingly, 8-week-old male mice (C57BL/6) were acclimated and bred for more than a week, and then dinitrobenzene sulfonic acid (DNBS; Sigma-Aldrich, USA) was administered to induce inflammatory bowel disease.
  • DNBS dinitrobenzene sulfonic acid
  • the experiment was conducted by classifying into a normal group without any treatment, a group administered with DNBS and distilled water (negative control group), and a group administered with DNBS and each mixed herbal extract (Hwangryeon, Hyeonggae, Baekduong, Hanryeoncho) (experimental group).
  • the survival rate was compared when DNBS was administered alone, and when DNBS and the complex herbal extract of the present invention were administered.
  • DNBS was dissolved in 50% ethanol aqueous solution to prepare a DNBS solution of 40 mg/mL. 0.1 mL of the prepared DNBS solution was slowly injected into the rectum of the mouse using a catheter.
  • the experimental group was administered once/day for 14 days from the start of the experiment at the dose (mg/kg) of each herbal extract prepared in the above Preparation Example.
  • DAI disease activity index
  • mice were classified into administration groups as shown in Fig. 4, each sample was administered. The next day after the start of the experiment, the weight of the mice in each group was measured and calculated as a weight loss rate, and the stool state and the presence of blood stool were checked. For the three indices, the DAI value was estimated by calculating the score according to the criteria in Table 1 of Example 1.
  • the complex herbal extracts exhibited excellent inflammatory bowel disease improvement or therapeutic effect.
  • the effect of protecting the barrier against inflammatory bowel disease of the mixed herbal medicine extract was confirmed.
  • the normal group without any treatment the DSS and distilled water administration group (negative control group), the DSS and 5-ASA administration group (positive control group), DSS and each mixed herbal medicine
  • the experiment was conducted by classifying the extracts (Hwangnyeon, Hyeonggae, Baekduong, Hanryeoncho) into the group administered (experimental group).
  • the positive control group was orally administered 5-ASA diluted in negative water at a dose of 25 mg/kg once/day for 9 days from the start of the experiment.
  • each herbal extract prepared in Preparation Example was mixed and administered at the dose (mg/kg) shown in Table 6, and was administered orally once/day for 9 days from the start of the experiment.
  • mice Thereafter, intestinal permeability was measured in mice.
  • FITC-dextran Sigma, USA
  • FITC-dextran Sigma, USA
  • mice were water-saved and fasted for 4 hours.
  • blood was collected through an orbital vein plexus, and only serum was separated to measure fluorescence, and the results are shown in Table 6 and FIG. 5.
  • the group (No. 5 and No. 7) administered with Baek Duong (15 mg/kg) or Hanryeoncho (50 mg/kg) to the mixed extract of Coptis Coptisium and Hyeonggae showed the fluorescence transmittance values of the normal group.
  • the barrier protection effect of the simultaneous mixed administration group of Baekduong or Hanryeoncho is superior compared to the mixed extract of Coptis Coptisium and Hyeonggae.
  • the efficacy of the treatment of DSS-induced inflammatory bowel disease was compared and evaluated between a single herbal extract and a mixed herbal extract.
  • the normal group without any treatment the DSS and distilled water administration group (negative control group), the DSS and 5-ASA administration group (positive control group), DSS and each single herbal medicine
  • the experiment was performed by classifying the extract or mixed herbal extracts (Hwangryeon, Hyeonggae, Baekduong, Hanryeoncho) into a group administered (experimental group).
  • the positive control group was orally administered 5-ASA diluted in negative water at a dose of 25 mg/kg once/day for 9 days from the start of the experiment.
  • each herbal extract prepared in Preparation Example was mixed and administered at the dose (mg/kg) shown in Table 7, and it was administered orally once/day for 9 days from the start of the experiment.
  • DAI Disease Activity Index
  • Intestinal permeability was measured in mice. On the 9th day of DSS induction, FITC-dextran (Sigma, USA) was orally administered at a concentration of 150 mg/ml to 100 ⁇ l per head to the mice that were water-saved and fasted for 4 hours. After 3 hours, blood was collected through an orbital vein plexus, and only serum was separated and fluorescence was measured. The results are shown in Table 8 and Fig. 7.
  • the group (No. 8 and No. 9) administered by mixing Baekduong or Hanryeoncho to the mixed extract of Hyeonggae and Hyeonggae showed the fluorescence transmittance values of the normal group.
  • the group administered with Coptis Coptis or Baekduong (No. 8 and No. 9) to the mixed extract of C It can be seen that is excellent.
  • 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 manufacturing method.
  • the above ingredients are mixed and filled into gelatin capsules to prepare a capsule.
  • liquid formulation According to the usual preparation method of the liquid formulation, add and dissolve each component in purified water, add an appropriate amount of lemon flavor, mix the above ingredients, add purified water, add purified water, adjust the total to 100 ml, and fill in a brown bottle. It is sterilized to prepare a liquid formulation.
  • Vitamin A acetate 70 ⁇ g
  • Vitamin B6 0.5 mg
  • Vitamin B12 0.2 ⁇ g
  • composition ratio of the vitamin and mineral mixture is relatively suitable for health food, but it may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. , To prepare granules, and can be used for preparing a health food composition according to a conventional method.
  • the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized, and stored in a refrigerator. It is used in the manufacture of the health beverage composition of the invention.
  • 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.

Abstract

The present invention provides a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease, comprising, as an active ingredient, a herbal medicine extract of: Coptis chinensis; Schizonepeta; and Eclipta prostrata L. or Pulsatilla chinensis regel. In addition, the present invention relates to a food composition or animal feed composition for the prevention or treatment of inflammatory bowel disease, comprising the herbal medicine extract as an active ingredient.

Description

복합 생약 추출물을 포함하는 염증성 장질환의 예방 또는 치료용 조성물Composition for preventing or treating inflammatory bowel disease comprising extracts of complex herbal medicines
본 발명은 황련; 형개; 및 한련초 또는 백두옹의 복합 생약 추출물을 유효성분으로 포함하는, 염증성 장질환의 예방 또는 치료용 약제학적 조성물을 제공한다. 또한 본 발명은 상기 복합 생약 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 개선용 식품 조성물 또는 사료 조성물에 관한 것이다.The present invention is Coptis; Brotherhood; And it provides a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease, comprising a complex herbal extract of nasturtium or baekduong as an active ingredient. In addition, 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.
본 특허출원은 2019년 10월 10일에 대한민국 특허청에 제출된 대한민국 특허출원 제10-2019-0125721호에 대하여 우선권을 주장하며, 상기 특허출원의 개시 사항은 본 명세서에 참조로서 삽입된다.This patent application claims priority to Korean Patent Application No. 10-2019-0125721 filed with the Korean Intellectual Property Office on October 10, 2019, and the disclosure of the patent application is incorporated herein by reference.
염증성 장질환(Inflammatory bowel disease)은 대장 및 소장의 점막에서 만성적인 염증 또는 궤양이 발생하여 설사 및 혈변이 나타나고, 일시적으로 증상이 좋아지다가 재발이 반복되는 만성 난치성 질환이다. 염증성 장질환은 임상적으로는 유사하지만, 조직학적 소견, 내시경 및 면역학적 측면에서 서로 다른 궤양성 대장염(ulcerative colitis) 및 크론병(Crohn's disease)의 두 가지 질환으로 분류된다. 궤양성 대장염은 대장의 점막에 진무름(미란)이나 궤양이 연속적으로 형성되는 질환으로 증상이 대장에서만 국한되어 나타나고, 혈변, 점혈변, 설사, 복통이 일어나며, 중증인 경우에는 발열, 체중감소, 빈혈 등의 전신성 증상이 나타난다. 크론병은 입에서 항문에 이르는 소화관의 임의 부위에 궤양 등의 병변이 비연속적으로 발생하는 질환으로서, 복통, 설사, 혈변과 더불어, 중증의 경우에는 발열, 체중감소, 전신 권태감, 빈혈 등의 증상이 나타난다. 이러한 염증성 장질환의 정확한 병인은 완전히 밝혀지지 않았지만, 환경적 또는 유전적 요인과 함께 자가면역질환 등에 의해 염증성 매개 인자 및 면역세포의 활성화가 중요한 병인인 것으로 추정되고 있다. 장 면역계의 지속적이고 부적절한 활성화는 만성 점막염 염증을 유발하며, 특히 호중구, 대식세포, 림프구 및 비만세포의 침윤에 의한 점막 파괴 및 궤양을 초래한다.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, resulting in diarrhea and bloody stools, temporarily improving symptoms, and recurring. Inflammatory bowel disease is clinically similar, but classified into two diseases, ulcerative colitis and Crohn's disease, which are different in histological findings, endoscopy and immunological aspects. Ulcerative colitis is a disease in which soreness (erosion) or ulcers are continuously formed on the mucous membrane of the large intestine. Symptoms are limited only in the large intestine. Bloody stools, mucous stools, diarrhea, and abdominal pain occur. In severe cases, fever, weight loss, and anemia. Systemic symptoms such as back appear. 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.In addition to abdominal pain, diarrhea, and bloody stools, symptoms such as fever, weight loss, systemic malaise, and anemia in severe cases. Appears. The exact etiology of such inflammatory bowel disease has not been fully identified, but it is estimated that activation of inflammatory mediators and immune cells are important pathogens due to autoimmune diseases, along with environmental or genetic factors. Persistent and inappropriate activation of the intestinal immune system leads to chronic mucositis inflammation, especially mucosal destruction and ulcers by infiltration of neutrophils, macrophages, lymphocytes and mast cells.
현재 염증성 장질환의 치료를 위하여 글루코코르티코스테로이드 (glucocorticosteroid) 등의 스테로이드류, 설파살라진(sulfasalazine), 메살라진(mesalazine) 등의 5-아미노살리실산(5-aminosalicylic acid, 5-ASA) 계통 약물, TNF-α 단일클론항체 등 과도한 면역반응을 억제하는 약물이 사용되고 있지만, 근본적인 치료를 하지 못하고, 또한 완치를 기대할 수는 없는 실정이며, 이들 약물조차도 다양한 부작용이 보고되고 있다. 예를 들어, 아미노살리실산 제제인 설파살라진은 구역질, 구토, 식욕부진, 발진, 두통, 간장해, 백혈구 감소, 이상 적혈구, 단백뇨, 설사 등의 부작용이 보고되고 있고, 스테로이드제인 프레드니솔론은 위궤양이나 장기 사용에 의한 대퇴 골두 괴사 등 강한 부작용이 보고되고 있다. TNF-α 단일클론항체인 Infliximab는 1998년 미국 FDA로부터 크론병 치료제로 허가를 받은 후 크론병 환자들을 치료하기 위해 사용되었으나, 범혈구 감소, 약물유발 낭창, B 형 간염/결핵 재활성 등의 부작용이 나타나고 있다. 따라서, 현재 사용하고 있는 염증성 장질환 치료제보다 우수한 효과를 나타내고, 안전하고 부작용이 적은 새로운 염증성 장질환 치료제 개발이 절실히 요구된다.Currently, for the treatment of inflammatory bowel disease, steroids such as glucocorticosteroids, 5-aminosalicylic acid (5-ASA) drugs such as sulfasalazine and mesalazine, TNF- Drugs that suppress excessive immune responses such as α monoclonal antibodies are used, but fundamental treatment is not possible, and a cure cannot be expected, and even these drugs have reported various side effects. For example, sulfasalazine, an aminosalicylic acid, has been reported to have side effects such as nausea, vomiting, loss of appetite, rash, headache, liver injury, leukocytosis, abnormal red blood cells, proteinuria, and diarrhea. Strong side effects, such as necrosis of the femoral head, have been reported. Infliximab, a TNF-α monoclonal antibody, was used to treat Crohn's disease patients after being 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 safer and has fewer side effects than the currently used inflammatory bowel disease treatments.
한편, 황련(Coptis Rhizome)은 미나리아재비과(Ranunculaceae)의 다년생 초본식물인 생약재로서, 황련 Coptis japonica Makino, 중국황련 Coptis chinensis Franchet, 삼각엽황련 Coptis deltoidea C. Y. Cheng et Hsiao 또는 운련(雲連) Coptis teeta Wallich의 뿌리줄기로서 뿌리를 제거한 것이다. 황련은 열기를 식히고 습기를 말리는 것인 청열조습(淸熱燥濕), 화열(火熱)과 열결(熱結)을 풀어주면서 해독하는 것인 사화해독(瀉火解毒), 사화통강법(瀉火通降法)에 속하는 것으로 심(心)이나 위(胃)의 화열(火熱)을 제거(사심(瀉心))함과 동시에 번조(煩躁)한 것을 제거(제번(除煩))하는 것인 사심제번(瀉心除煩)에 효능이 있다. 또한, 온독, 창양열독(瘡瘍熱毒) 등의 병증에 사용하는 방법이 알려져 있고, 항미생물 작용, 혈압 강하 작용, 소염작용 등의 약리효과가 있는 것으로 알려져 있다.On the other hand, Coptis Rhizome is a medicinal herb that is a perennial herbaceous plant of the Ranunculaceae family. The roots are removed as the rootstock. Hwangryeon is to cool heat and dry moisture, detoxification while releasing heat and heat. Self-centeredness, which belongs to the 通降法), which removes the burning heat of the heart or stomach (self-heartedness) and at the same time removes the ones that have been dying (除煩). It is effective in Jebeon (瀉心除煩). In addition, methods for use in diseases such as ontoxication and changyang fever are known, and are known to have pharmacological effects such as antimicrobial action, blood pressure lowering action, and anti-inflammatory action.
형개(Schizonepeta tenuifolia Briquet)는 꿀풀과(Labiatae)에 속한 일년생 초목으로, 이의 지상부인 형개(Schizonepetae Herba) 또는 꽃이삭(꽃대)인 형개수(荊芥穗, Schizonepetae Spica)가 약용으로서 사용된다. 한방에서는 외감성으로 인한 오한, 열, 두통과 땀이 나는 증상에 쓰이고 부인이 산후 감기로 경련과 발작을 일으킬 때 단방으로 가루를 내어 복용하며, 피부가려움증에 유효하다. 창양초기에 열이 있고 염증이 확산될 때 활용하며, 까맣게 볶아서 쓰면 토혈, 변혈, 코피, 소변 출혈, 자궁 출혈에 지혈 효과를 나타낸다.Hyeonggae (Schizonepeta tenuifolia Briquet) is an annual plant belonging to the Lamiaceae family (Labiatae), and its above-ground part, Hyeonggae (Schizonepetae Herba) or the ear of flowers (Schizonepetae Spica), is used for medicinal purposes. In oriental medicine, it is used for the symptoms of chills, fever, headache and sweating due to external sensitivity. When a woman has convulsions and seizures due to a cold after childbirth, it is taken as a single powder and is effective for skin itching. It is used when there is a fever and inflammation spreads in the early stage of the window candle, and if it is roasted black, it has a hemostatic effect on hematopoiesis, bleeding, nosebleeds, urine bleeding and uterine bleeding.
한련초(Ecliptae Herba)는 국화과(Compositae)의 한해살이풀로, 한련초(Eclipta prostrata Linne)의 전초이다. 애장초, 목한련, 묵두초, 하련초 등으로도 불린다. 한련초는 지혈작용을 비롯하여 보음(補陰), 보신(補腎) 등의 효능을 가지고 있으며 근육과 뼈(筋骨)를 튼튼하게 해주는 것으로 알려져 있다.Hanryeoncho (Ecliptae Herba) is a perennial plant of the Asteraceae (Compositae), and is an outpost of the Hanryeoncho (Eclipta prostrata Linne). It is also called aejangcho, mokhannyeon, mukducho, and hayeoncho. Hanryeoncho has the effect of hemostasis, boeum (補陰) and boshin (補腎), and is known to strengthen muscles and bones.
백두옹(Pulsatillae Radix)은 노고초라고 불리며, 미나리아재비과(Ranunculaceae)에 속하는 다년생 초목인 할미꽃(Pulsatilla koreana Nakai) 또는 백두옹(Pulsatilla chinensis Regel) 등의 동속 근록식물의 뿌리를 건조한 것으로, 약리작용으로는 항균작용, 아메바원충과 음도원충 억제작용, 심장독성, 진정, 진통 작용, 피부점막자극작용 등이 보고되었다.Baek Duong (Pulsatillae Radix) is called Nogocho, and is a perennial plant belonging to the Ranunculaceae family, such as Pulsatilla koreana Nakai or Baek Duong (Pulsatilla chinensis Regel). , Amoeba protozoa and Eumdo protozoa inhibitory effect, cardiac toxicity, soothing, analgesic effect, and skin mucosa stimulating effect have been reported.
그러나 현재까지 황련, 형개, 한련초, 백두옹의 복합 생약 추출물이 염증성 장질환의 치료에 효과적으로 사용될 수 있는지는 공지된 바 없다.However, until now, it has not been known whether the complex herbal extracts of Hwangryeon, Hyeonggae, Hanryeoncho, and Baekduong can be effectively used in the treatment of inflammatory bowel disease.
본 발명자들은 염증성 장질환을 치료할 수 있는 방법을 개발하기 위하여 지속적인 연구를 거듭한 결과, 황련, 형개, 한련초, 백두옹의 복합 생약 추출물을 사용하였을 때, 각각의 단일 추출물을 사용하는 것 보다 더 우수한 치료 효과가 있음을 발견하여 본 발명을 완성하였다.As a result of continuous research in order to develop a method for treating inflammatory bowel disease, the present inventors performed better treatment than using each single extract when using complex herbal extracts of Hwangryeon, Hyeonggae, Hanryeoncho, and Baekduong. Having found that there is an effect, the present invention was completed.
따라서, 본 발명의 목적은 황련; 형개; 및 한련초 또는 백두옹의 생약 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 치료용 약제학적 조성물을 제공하는 것이다. Therefore, the object of the present invention is Cwangryun; Brotherhood; And it is to provide a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease comprising the herbal extract of nasturtium or baekduong as an active ingredient.
본 발명의 다른 목적은 황련; 형개; 및 한련초 또는 백두옹의 생약 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 개선용 식품 조성물 또는 사료 조성물을 제공하는 것이다. Another object of the present invention is Hwangnyeon; Brotherhood; And it is to provide a food composition or feed composition for preventing or improving inflammatory bowel disease, comprising the herbal extract of nasturtium or baekduong as an active ingredient.
본 발명의 또 다른 목적은 황련; 형개; 및 한련초 또는 백두옹의 생약 추출물을 유효성분으로 포함하는 약제학적 조성물 또는 식품 조성물을 대상체(subject)에 투여하는 단계를 포함하는 염증성 장질환의 예방, 개선 또는 치료방법을 제공하는 것이다. Another object of the present invention is Hwangnyeon; Brotherhood; And it is 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 nasturtium or baekduong as an active ingredient.
본원 명세서 전체에서, 어떤 부분이 어떤 구성 요소를 "포함" 한다고 할 때, 이는 특별히 반대되는 기재가 없는 한 다른 구성 요소를 제외하는 것이 아니라 다른 구성 요소를 더 포함할 수 있는 것을 의미한다.In the entire specification of the present application, when a certain part "includes" a certain constituent element, it means that other constituent elements may be further included rather than excluding other constituent elements unless otherwise specified.
본 발명의 일 양태에 따르면, 본 발명은 황련; 형개; 및 한련초 또는 백두옹의 생약 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 치료용약제학적 조성물을 제공한다.According to an aspect of the present invention, the present invention is Coptis; Brotherhood; And it provides a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease comprising the herbal extract of nasturtium or baekduong as an active ingredient.
본 명세서에서 용어 "생약 추출물" 또는 "복합 생약 추출물"은 본발명의 약제학적 조성물의 유효성분으로서, 황련, 형개, 한련초 또는 백두옹 추출물 각각을 포함하거나, 각 생약 혼합물로부터 추출된 추출물을 포함하는 것을 의미한다. In the present specification, the term "herbal extract" or "combined herbal extract" is an active ingredient of the pharmaceutical composition of the present invention, including each of Coptis chinensis, Hyeonggae, Hanryeoncho or Baekduong extract, or including extracts extracted from each herbal mixture it means.
본 발명의 "황련(Coptis Rhizome)"은 미나리아재비과(Ranunculaceae)의 다년생 초본식물인 생약재를 의미하며, 황련 Coptis japonica Makino, 중국황련 Coptis chinensis Franchet, 삼각엽황련 Coptis deltoidea C. Y. Cheng et Hsiao 또는 운련 (雲連) Coptis teeta Wallich의 뿌리줄기로서 뿌리를 제거한 것을 지칭한다. "Coptis Rhizome" of the present invention means a herbaceous perennial herbaceous plant of Ranunculaceae, Coptis japonica Makino, Coptis chinensis Franchet, Triangular Leaf Coptis deltoidea CY Cheng et Hsiao or Woonryeon (雲連) It is the rootstock of Coptis teeta Wallich and refers to the root removed.
본 발명의 "형개(Schizonepeta tenuifolia Briquet)"는 꿀풀과(Labiatae)에 속한 일년생 초목을 의미하며, 이의 지상부인 형개(Schizonepetae Herba) 또는 꽃이삭(꽃대)인 형개수(荊芥穗, Schizonepetae Spica)를 포함한다. "Hyunggae (Schizonepeta tenuifolia Briquet)" of the present invention means an annual vegetation belonging to the Lamiaceae family (Labiatae), and includes Hyeonggae (Schizonepetae Herba) or the ear of flowers (Schizonepetae Spica), which is the above-ground part thereof do.
본 발명의 "한련초(Ecliptae Herba)"는 국화과(Compositae)의 한해살이풀을 의미하며, 한련초(Eclipta prostrata Linne)의 전초로서, 애장초, 목한련, 묵두초, 하련초 등으로도 불리는 것을 지칭한다."Ecliptae Herba" of the present invention refers to the annual herb of the chrysanthemum family (Compositae), and refers to what is also called aejangcho, mokhanryeon, mukducho, haliancho, etc. .
본 발명의 "백두옹(Pulsatillae Radix)"은 노고초라고 불리며, 미나리아재비과(Ranunculaceae)에 속하는 다년생 초목인 할미꽃(Pulsatilla koreana Nakai) 또는 백두옹(Pulsatilla chinensis Regel) 등의 동속 근록식물의 뿌리를 건조한 것을 지칭한다."Baek Duong (Pulsatillae Radix)" of the present invention is called Nogocho, and refers to the drying of the roots of plants of the same genus such as Pulsatilla koreana Nakai or Pulsatilla chinensis Regel, a perennial plant belonging to Ranunculaceae. .
본 명세서에서 용어 "염증성 장질환"은 창자, 즉 작은창자, 큰창자 등에 염증이 생기는 질환을 의미하며, 장관 내 비정상적인 만성 염증이 호전과 재발을 반복하는 질환을 포함한다. 또한, 원인이 밝혀진 특이성 장염, 원인이 밝혀지지 않은 비특이성 장염, 및 타질환으로부터 야기된 장염, 예를 들어 장형 베체트병 등을 포함한다.In the present specification, the term "inflammatory bowel disease" refers to a disease in which inflammation occurs in the intestine, ie, small intestine, large intestine, etc., and includes a disease in which abnormal chronic inflammation in the intestine repeats improvement and recurrence. In addition, it includes specific enteritis of which the cause has been identified, non-specific enteritis of which the cause is not known, and enteritis caused by other diseases, for example, enteric Behcet's disease, and the like.
본 명세서에서 용어 "치료"는 본 발명에 따른 조성물의 투여로 염증성 장질환의 증상이 호전되거나 완치되는 모든 행위를 의미한다. In the present specification, the term "treatment" refers to all actions in which symptoms of inflammatory bowel disease are improved or cured by administration of the composition according to the present invention.
본 명세서에서 용어 "예방"은 본 발명에 따른 조성물의 투여로 염증성 장질환의 증상을 억제 또는 지연시키는 모든 행위를 의미한다.In the present specification, the term "prevention" refers to any action that suppresses or delays symptoms of inflammatory bowel disease by administration of the composition according to the present invention.
본 명세서에서 용어 "유효성분으로 포함하는"이란, 본 발명 추출물의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. As used herein, the term "including as an active ingredient" means including an amount sufficient to achieve the efficacy or activity of the extract of the present invention.
본 발명의 상기 약제학적 조성물은 본 발명의 조성물이 나타내는 것과 동일하거나 유사한 효과를 갖는 것으로 당업계에 알려져 있는 다른 생약의 추출물을 추가로 포함할 수 있다.The pharmaceutical composition of the present invention may further include an extract of another herbal medicine known in the art to have the same or similar effect as that of the composition of the present invention.
본 발명의 상기 약제학적 조성물은 당업계에 염증성 장질환 치료 효과가 있는 것으로 알려져 있는 유효 성분을 추가로 포함할 수 있다. 보다 구체적으로, 상기 약제학적 조성물은 글루코코르티코스테로이드(glucocorticosteroid) 등의 스테로이드류, 설파살라진(sulfasalazine), 메살라진(mesalazine) 등의 5-아미노살리실산(5-aminosalicylic acid, 5-ASA) 계통 약물, TNF-α 단일클론항체로 이루어진 군으로부터 선택되는 1종 이상의 유효 성분을 추가로 포함할 수 있다.The pharmaceutical composition of the present invention may further contain an active ingredient known to have an effect on treating inflammatory bowel disease in the art. More specifically, the pharmaceutical composition includes steroids such as glucocorticosteroids, 5-aminosalicylic acid (5-ASA) drugs such as sulfasalazine and mesalazine, and TNF -α may further contain one or more active ingredients selected from the group consisting of monoclonal antibodies.
본 발명의 상기 약제학적 조성물은 염증성 장질환 외 다른 질환에 효과를 나타내는 유효성분을 추가로 포함할 수 있다.The pharmaceutical composition of the present invention may further include an active ingredient showing an effect on diseases other than inflammatory bowel disease.
본 발명의 생약 추출물이 추가의 유효성분과 함께 사용되는 경우, 생약 추출물 및 추가의 유효성분은 하나의 제형으로 동시에 투여되거나, 또는 별개의 제형으로 동시에 또는 순차적으로 투여되는 것일 수 있다.When the herbal extract of the present invention is 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.
본 발명의 상기 약제학적 조성물은 염증성 장질환을 치료하기 위하여 단독 또는 수술, 호르몬 치료, 약물 치료 또는 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The pharmaceutical composition of the present invention may be used alone or in combination with surgery, hormone therapy, drug therapy, or methods of using a biological response modifier to treat inflammatory bowel disease.
본 발명에 이용되는 생약 추출물은 당업계에서 공지된 통상적인 추출용매를 이용하여 얻을 수 있다. 추출용매로는 극성 용매 또는 비극성 용매를 이용할 수 있다. 극성 용매로는 물, C1 내지 C6의 알코올(예: 메탄올, 에탄올, 프로판올, 부탄올, 노말-프로판올, 이소-프로판올 및 노말-부탄올 등), 아세트산, 또는 상기 극성 용매들의 혼합물을 포함한다. 비극성 용매로는 아세톤, 아세토나이트릴, 에틸아세테이트, 메틸아세테이트, 부틸아세테이트, 플루오로알칸, 헥산, 에테르, 클로로포름, 디클로로메탄 또는 상기 비극성 용매들의 혼합물을 포함한다.The herbal extract used in the present invention can be obtained using a conventional extraction solvent known in the art. As the extraction solvent, a polar solvent or a non-polar solvent may be used. Polar solvents include water, C1 to C6 alcohols (eg, methanol, ethanol, propanol, butanol, normal-propanol, iso-propanol and normal-butanol, etc.), acetic acid, or a mixture of the 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.
본 발명의 일 구현예에 있어서, 상기 생약 추출물은 물, C1 내지 C6의 알코올, 아세트산 및 이들의 혼합 용매로 이루어지는 군으로부터 선택되는 용매로 추출된 것이다. In one embodiment of the present invention, the herbal extract is extracted with a solvent selected from the group consisting of water, C1 to C6 alcohol, acetic acid, and a mixed solvent thereof.
본 발명의 일 구체예에 있어서, 상기 생약 추출물은 0.01 내지 90% 에탄올로 추출된 것이다. 보다 구체적으로, 상기 생약 추출물은 0.01 내지 90%, 1 내지 90%, 10 내지 90%, 20 내지 90%, 30 내지 90%, 40 내지 90%, 50 내지 90%, 60 내지 90%, 0.01 내지 80%, 1 내지 80%, 10 내지 80%, 20 내지 80%, 30 내지 80%, 40 내지 80%, 50 내지 80% 에탄올로 추출된 것이다. 가장 구체적으로 상기 생약 추출물은 60 내지 80% 에탄올로 추출된 것이다. In one embodiment of the present invention, 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 It is extracted with 80%, 1 to 80%, 10 to 80%, 20 to 80%, 30 to 80%, 40 to 80%, 50 to 80% ethanol. Most specifically, the herbal extract is extracted with 60 to 80% ethanol.
본 발명의 일 구현예에 있어서, 상기 생약 추출물은 열수 추출, 냉침 추출, 환류 냉각 추출, 초음파 추출 또는 당업계에 알려진 통상적인 추출방법을 통해 추출한 것이다.In one embodiment of the present invention, the herbal extract is extracted through hot water extraction, cold needle extraction, reflux cooling extraction, ultrasonic extraction, or conventional extraction methods known in the art.
본 명세서에서 사용된 용어 "추출물"은 당업계에서 조추출물(crude extract)로 통용되는 의미를 갖지만, 광의적으로 추출물을 추가적으로 분획(fractionation)한 분획물도 포함한다. 즉 생약 추출물은 상술한 용매를 이용하여 얻은 것뿐만 아니라, 여기에 정제 과정을 추가적으로 적용하여 얻은 것을 포함한다. 예컨대, 상기 추출물을 일정한 분자량 컷-오프 값을 갖는 한외여과막을 통과시켜 얻은 분획, 다양한 크로마토그래프(크기, 전하, 소수성 또는 친화성에 다른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 정제 방법을 통해 얻어진 분획도 본 발명의 생약 추출물에 포함된다.The term "extract" as used herein has a meaning commonly used as a crude extract in the art, but also includes a fraction obtained by further fractionating the extract in a broad sense. That is, the herbal extract includes not only those obtained by using the above-described solvent, but also those obtained by additionally applying a purification process thereto. For example, fractions obtained by passing the extract through an ultrafiltration membrane having a certain molecular weight cut-off value, separation by various chromatographs (made for different separation in size, charge, hydrophobicity or affinity), etc. Fractions obtained through the purification method are also included in the herbal extract of the present invention.
본 발명의 약제학적 조성물은 약제학적으로 허용되는 담체를 포함할 수 있다. 상기 약제학적으로 허용되는 담체는 제제시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. 본 발명의 약제학적 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다. 적합한 약제학적으로 허용되는 담체 및 제제는 Remington's Pharmaceutical Sciences (19th ed., 1995)에 상세히 기재되어 있다.The pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier is commonly used in the formulation, lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, and the like, but are not limited thereto. 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. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).
본 발명의 일 구현예에 있어서, 상기 염증성 장질환은 크론병, 궤양성 대장염, 장형 베체트병, 장결핵, 출혈성 직장 궤양, 불확정 대장염(indeterminate colitis), 세균성 장염, 바이러스성 장염, 아메바성 장염 및 허혈성 대장염으로 이루어진 군으로부터 선택되는 질환인 것이다. In one embodiment of the present invention, the inflammatory bowel disease is Crohn's disease, ulcerative colitis, long Behcet's disease, intestinal tuberculosis, hemorrhagic rectal ulcer, indeterminate colitis, bacterial enteritis, viral enteritis, amoebic enteritis and ischemic It is a disease selected from the group consisting of colitis.
본 발명의 일 구현예에 있어서, 상기 약제학적 조성물은 분말, 과립, 정제, 피복정제, 환제, 당의정제, 캡슐제, 액제, 현탁액제, 겔제, 시럽제, 슬러리제, 좌약, 관장제, 에멀전제, 페이스트제(pastes), 연고제, 크림제, 로션제, 산제, 분무제 또는 현탁액으로 제형화될 수 있다.In one embodiment of the present invention, the pharmaceutical composition is powder, granule, tablet, coated tablet, pill, dragee, capsule, liquid, suspension, gel, syrup, slurry, suppository, enema, emulsion, It can be formulated as pastes, ointments, creams, lotions, powders, sprays or suspensions.
본 발명의 일 구현예에 있어서, 상기 약제학적 조성물은 경구 투여를 위하여 정제, 환제, 산제, 과립제 또는 캡슐제 등의 고형제제 또는 현탁제, 내용액제, 유제 또는 시럽제 등의 액상제제로 제형화 될 수 있다. 또는 상기 약제학적 조성물을 비경구 투여를 위하여 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제 또는 좌제 등으로 제형화될 수 있다.In one embodiment of the present invention, the pharmaceutical composition may be formulated as a solid preparation such as a tablet, a pill, a powder, a granule or a capsule, or a suspension, a liquid solution, an emulsion, or a syrup for oral administration. I can. Alternatively, the pharmaceutical composition may be formulated as a sterilized aqueous solution, a non-aqueous solution, a suspension, an emulsion, a lyophilized agent, or a suppository for parenteral administration.
본 발명의 일 구현예에 있어서, 상기 약제학적 조성물은 약제학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 또는 희석제를 추가로 포함할 수 있다. 예를 들면, 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 만니톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 또는 광물유 등이다. In one embodiment of the present invention, the pharmaceutical composition may further include an appropriate carrier, excipient, or diluent commonly used in the manufacture of pharmaceutical compositions. For example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, mannitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl Pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil.
본 발명의 일 구현예에 있어서, 상기 생약 추출물은 황련; 형개; 및 한련초 또는 백두옹이 0.05-20 : 0.05-20 : 0.05-20 중량비로 혼합된 것이다. 보다 구체적으로, 상기 생약 추출물은 황련; 형개; 및 한련초 또는 백두옹이 1-10 : 1-10 : 1-10, 1 : 1-10 : 1-10, 1-10 : 1 : 1-10, 1-10 : 1-10 : 1, 3 : 1-10 : 1-10, 1-10 : 3 : 1-10, 1-10 : 1-10 : 3, 10 : 1-10 : 1-10, 1-10 : 10 : 1-10, 1-10 : 1-10 : 10, 1 : 1 : 1-10, 3 : 1 : 1-10, 10 : 1 : 1-10, 1 : 3 : 1-10, 1 : 10 : 1-10, 3 : 3 : 1-10, 3 : 10 : 1-10, 10 : 10 : 1-10 중량비로 혼합된 것이다. In one embodiment of the present invention, the herbal extract is Hwangnyeon; Brotherhood; And nasturtium or baekduongi are mixed in a weight ratio of 0.05-20: 0.05-20: 0.05-20. More specifically, the herbal extract is Hwangryeon; Brotherhood; And nasturtium or baekduongi 1-10: 1-10: 1-10, 1: 1-10: 1-10, 1-10: 1: 1-10, 1-10: 1-10: 1, 3: 1 -10: 1-10, 1-10: 3: 1-10, 1-10: 1-10: 3, 10: 1-10: 1-10, 1-10: 10: 1-10, 1-10 : 1-10: 10, 1: 1: 1-10, 3: 1: 1-10, 10: 1: 1-10, 1: 3: 1-10, 1: 10: 1-10, 3: 3 : 1-10, 3:10: 1-10, 10:10: 1-10 It is mixed in a weight ratio.
가장 구체적으로, 상기 생약 추출물은 황련; 형개; 및 한련초 또는 백두옹이 10 : 1 : 1-10 중량비로 혼합된 것이다.Most specifically, the herbal extract is Hwangnyeon; Brotherhood; And nasturtium or baekduongi 10:1: 1-10 is mixed in a weight ratio.
본 발명의 실시예에 따르면, 상기 생약 추출물은 황련; 형개; 및 한련초 또는 백두옹이 10:1:1, 10:1:3, 10:1:10 중량비로 혼합되는 경우 효과가 우수하다. According to an embodiment of the present invention, the herbal extract is Coptis Coptis; Brotherhood; And when nakryeoncho or baekduong is mixed in a weight ratio of 10:1:1, 10:1:3, and 10:1:10, the effect is excellent.
본 발명의 약제학적 조성물의 적합한 투여량은 제제화 방법, 투여방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하며, 보통으로 숙련된 의사는 소망하는 치료 또는 예방에 효과적인 투여량을 용이하게 결정 및 처방할 수 있다. 본 발명의 바람직한 구현예에 따르면, 본 발명의 약제학적 조성물의 1일 투여량은 1-100 ㎎/㎏이다.A suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, mode of administration, age, weight, sex, pathological condition, food, administration time, route of administration, excretion rate and response sensitivity of the patient, Usually the skilled practitioner can readily determine and prescribe a dosage effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 1-100 mg/kg.
본 발명의 다른 양태에 따르면, 본 발명은 황련; 형개; 및 한련초 또는 백두옹의 생약 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 개선용 식품 조성물을 제공한다. According to another aspect of the present invention, the present invention is Coptis; Brotherhood; And it provides a food composition for preventing or improving inflammatory bowel disease, comprising the herbal extract of nasturtium or baekduong as an active ingredient.
본 명세서에서 용어 "개선"은 본 발명의 추출물을 포함하는 조성물의 투여로 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 감소시키는 모든 행위를 의미한다.As used herein, the term "improvement" refers to all actions of reducing the severity of a parameter, for example, symptoms related to a condition to be treated by administration of a composition comprising an extract of the present invention.
본 발명의 식품 조성물은 분말, 과립, 정제, 캡슐 또는 음료 등의 형태로 제조될 수 있다. 예컨대 캔디류의 각종 식품류, 음료, 껌, 차, 비타민 복합제, 또는 건강보조 식품류 등이 있다.The food composition of the present invention may be prepared in the form of powder, granules, tablets, capsules or beverages. For example, there are various foods such as candy, beverages, gum, tea, vitamin complexes, or health supplement foods.
본 발명의 식품 조성물은 건강기능식품 및 건강식품 등을 포함한다.The food composition of the present invention includes health functional foods and health foods.
본 발명의 식품 조성물은 장기 복용할 수 있다.The food composition of the present invention can be taken for a long time.
본 발명의 식품 조성물은 식품 제조 시에 통상적으로 첨가되는 성분을 포함할 수 있으며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등]) 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수있다. 예컨대, 본 발명의 식품 조성물이 드링크제로 제조되는 경우에는 본 발명의 황련 및 형개 혼합 추출물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 두충 추출액, 대추 추출액, 감초 추출액 등을 추가로 포함할 수 있다.The food composition of the present invention may include ingredients that are commonly added during food production, and include, for example, proteins, carbohydrates, fats, nutrients, flavoring agents, and flavoring agents. Examples of the aforementioned carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents, natural flavoring agents [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.]) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared as a drink, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, cephalic extract, jujube extract, licorice extract, etc. Can include.
본 발명의 또 다른 양태에 따르면, 본 발명은 황련; 형개; 및 한련초 또는 백두옹의 생약 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 개선용 사료 조성물을 제공한다. According to another aspect of the present invention, the present invention is Coptis; Brotherhood; And it provides a feed composition for preventing or improving inflammatory bowel disease, comprising the herbal extract of nasturtium or baekduong as an active ingredient.
발명의 조성물에 포함된 황련, 형개, 한련초, 및 백두옹 추출물은 천연식물재료로서, 오랫동안 식용 및 민간약으로 사용되어 왔던 것이므로 이로부터 추출된 본 발명의 추출물 역시 독성 및 부작용 등의 문제가 없을 것으로 예상할 수 있다. 따라서, 황련, 형개, 한련초, 및 백두옹 추출물은 의약품, 식품 조성물, 사료 조성물로 사용될 수 있다.The extracts of Coptis Rhizoma, Hyeonggae, Hanryeoncho, and Baekduong contained in the composition of the present invention are natural plant materials, and have been used as edible and folk medicine for a long time, so it is expected that the extract of the present invention extracted from them will also have no problems such as toxicity and side effects. I can. Therefore, the extracts of Coptisaceae, Hyeonggae, Hanryeoncho, and Baekduong can be used as pharmaceuticals, food compositions, and feed compositions.
본 발명의 식품 조성물 및 사료 조성물에 포함되는 황련, 형개, 한련초, 및 백두옹 추출에 관한 내용은 상기 약제학적 조성물에 포함되는 혼합 추출물의 추출에 관한 내용과 동일하기 때문에, 이 둘 사이에 공통된 내용은 본 명세서의 과도한 복잡성을 피하기 위하여, 그 기재를 생략한다.Since the contents of the extract of Coptis chinensis, Hyeonggae, Hanryeoncho, and Baekduong contained in the food composition and feed composition of the present invention are the same as the contents of the extraction of the mixed extract contained in the pharmaceutical composition, the contents in common between the two are In order to avoid excessive complexity of the present specification, description thereof is omitted.
본 발명의 또 다른 양태에 따르면, 본 발명은 상술한 본 황련; 형개; 및 한련초 또는 백두옹의 혼합 추출물을 유효성분으로 포함하는 약제학적 조성물 또는 식품 조성물을 대상체(subject)에 투여하는 단계를 포함하는 염증성 장질환의 예방, 개선 또는 치료방법을 제공한다. According to another aspect of the present invention, the present invention includes the above-described present Coptis Coptis; Brotherhood; And it provides a method for preventing, improving or treating inflammatory bowel disease comprising administering to a subject a pharmaceutical composition or a food composition comprising a mixed extract of nasturtium or baekduong as an active ingredient.
본 명세서에서 사용된 용어, "투여" 또는 "투여하다"는 본 발명의 조성물의 치료적, 또는 예방적 유효량을 상기 대상 질환을 겪거나, 겪을 가능성이 있는 대상체(개체)에 직접적으로 투여함으로써 대상체의 체내에서 동일한 양이 형성되도록 하는 것을 의미한다. 본 발명의 조성물의 투여경로는 목적 조직에 도달할 수 있는 한 일반적인 모든 경로를 통하여 경구 또는 비 경구 투여될 수 있다. 또한, 본 발명의 조성물은 유효성분을 표적 세포, 조직 또는 기관으로 전달할 수 있는 임의의 장치를 이용해 투여될 수도 있다.As used herein, the term "administering" or "administering" refers to a subject by directly administering a therapeutically or prophylactically effective amount of a composition of the present invention to a subject (individual) suffering from or likely to suffer from the subject disease. It means to ensure that the same amount is formed in the body. The administration route of the composition of the present invention may be administered orally or parenterally through any general route as long as it can reach the target tissue. In addition, the composition of the present invention may be administered using any device capable of delivering the active ingredient to target cells, tissues or organs.
상기 조성물의 "치료적 유효량"은 조성물을 투여하고자 하는 대상체에게 치료적 또는 예방적 효과를 제공하기에 충분한 조성물의 함량을 의미하며, 이에 "예방적 유효량"을 포함하는 의미이다.The "therapeutically effective amount" of the composition means an amount of the composition sufficient to provide a therapeutic or prophylactic effect to a subject to which the composition is to be administered, and is meant to include a "prophylactically effective amount".
본 발명의 일 구현예에 있어서, 상기 대상체는 인간, 원숭이, 소, 말, 양, 돼지, 닭, 칠면조, 메추라기, 고양이, 개, 마우스, 랫트, 토끼 및 기니아 피그로 이루어지는 군으로부터 선택되는 것이나 이에 한정되는 것은 아니다. 보다 구체적으로, 상기 대상체는 인간이다. In one embodiment of the present invention, the subject is selected from the group consisting of humans, monkeys, cows, horses, sheep, pigs, chickens, turkeys, quails, cats, dogs, mice, rats, rabbits, and guinea pigs. It is not limited. More specifically, the subject is a human.
본 발명의 예방, 방법의 대상 질병인 염증성 장질환은 상기 약제학적 조성물 또는 식품 조성물의 대상 질병과 관련하여 정의한 것과 같다.Inflammatory bowel disease, which is the target disease of the prevention and method of the present invention, is the same as defined in relation to the target disease of the pharmaceutical composition or food composition.
본 발명의 상기 염증성 장질환의 예방 또는 치료방법은, 본 발명의 일 양태인 약제학적 조성물을 투여하는 단계를 포함하는 방법이므로, 상기 약제학적 조성물과 관련하여 중복되는 내용에 대해서는 본 명세서의 과도한 중복성을 피하기 위하여 그 기재를 생략한다.Since the method for preventing or treating inflammatory bowel disease of the present invention is a method comprising administering a pharmaceutical composition, which is an aspect of the present invention, excessive redundancy in the present specification for overlapping contents with respect to the pharmaceutical composition The description is omitted in order to avoid.
본 발명의 혼합 생약 추출물을 유효성분으로 포함하는 약제학적 조성물은 염증성 장질환, 특히 크론병 또는 궤양성 대장염에 있어서 우수한 치료 효과를 나타내어, 신규한 치료제로 사용될 수 있다.The pharmaceutical composition comprising the mixed herbal extract of the present invention as an active ingredient exhibits excellent therapeutic effect in inflammatory bowel disease, particularly Crohn's disease or ulcerative colitis, and can be used as a novel therapeutic agent.
또한, 본 발명의 약제학적 조성물은 천연물을 유효성분으로 포함함으로써 기존 치료제의 부작용을 줄이고 안전한 치료제로 사용될 수 있다.In addition, the pharmaceutical composition of the present invention can be used as a safe therapeutic agent to reduce side effects of existing therapeutic agents by including a natural product as an active ingredient.
도 1은 DSS 유도 염증성 장질환 모델에서 측정한 각 투여군의 DAI 값을 나타낸다.1 shows the DAI value of each administration group measured in the DSS-induced inflammatory bowel disease model.
도 2는 DSS 유도 염증성 장질환 모델에서 측정한 각 투여군의 대장의 길이를 나타낸다.Figure 2 shows the length of the colon of each administration group measured in the DSS-induced inflammatory bowel disease model.
도 3은 DNBS 유도 염증성 장질환 모델에서 측정한 각 투여군의 생존율을 나타낸다.Figure 3 shows the survival rate of each administration group measured in the DNBS-induced inflammatory bowel disease model.
도 4는 DNBS 유도 염증성 장질환 모델에서 측정한 각 투여군의 DAI 값을 나타낸다.Figure 4 shows the DAI value of each administration group measured in the DNBS-induced inflammatory bowel disease model.
도 5는 DSS 유도 염증성 장질환 모델에서 측정한 각 투여군의 장 투과도를 나타낸다.5 shows the intestinal permeability of each administration group measured in the DSS-induced inflammatory bowel disease model.
도 6는 DSS 유도 염증성 장질환 모델에서 측정한 각 투여군의 DAI 값을 나타낸다.6 shows the DAI values of each administration group measured in the DSS-induced inflammatory bowel disease model.
도 7는 DSS 유도 염증성 장질환 모델에서 측정한 각 투여군의 장 투과도를 나타낸다.7 shows the intestinal permeability of each administration group measured in the DSS-induced inflammatory bowel disease model.
도 8는 DSS 유도 염증성 장질환 모델에서 측정한 각 투여군의 대장의 길이를 나타낸다.8 shows the length of the colon of each administration group measured in the DSS-induced inflammatory bowel disease model.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for describing the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
실시예Example
본 명세서 전체에 걸쳐, 특정 물질의 농도를 나타내기 위하여 사용되는 "%"는 별도의 언급이 없는 경우, 고체/고체는 (중량/중량) %, 고체/액체는 (중량/부피) %, 그리고 액체/액체는 (부피/부피) %이다.Throughout this specification, "%" used to indicate the concentration of a specific substance is (weight/weight)% for solids/solids, (weight/volume)% for solids/liquids, and Liquid/liquid is (vol/vol) %.
제조예Manufacturing example
세척 및 건조된 황련(Coptis Rhizome), 형개(Schizonepetae Spica 및 Schizonepetae Herba), 한련초(Ecliptae Herba), 백두옹(Pulsatillae Radix)을 실험에 사용하였다. 상기 황련, 형개, 한련초, 백두옹 생약 각 75 g에 10배의 70 %(v/v) 에탄올 수용액을 가하여 상온에서 72시간 동안 교반시킨 후 추출액을 수득하였다. 그 후, 각각의 추출액을 여과하여 50 내지 65℃에서 감압농축하고, 동결건조하여 분말 상태의 단일 생약 추출물을 수득하였다.Washed and dried Coptis Rhizome, Hyeonggae (Schizonepetae Spica and Schizonepetae Herba), Hanryeoncho (Ecliptae Herba), Baek Duong (Pulsatillae Radix) were used in the experiment. An extract was obtained after adding 10 times of 70% (v/v) aqueous ethanol solution to 75 g of the Coptis Coptisium, Hyeonggae, Hanryeoncho, and Baekduong herbal medicines, followed by stirring at room temperature for 72 hours. Thereafter, each extract was filtered, concentrated under reduced pressure at 50 to 65°C, and freeze-dried to obtain a powdery single herbal extract.
실험예 1: DSS 유도 염증성 장질환 모델에서의 혼합 생약 추출물의 치료 효능Experimental Example 1: Treatment Efficacy of Mixed Herbal Extracts in DSS Induced Inflammatory Bowel Disease Model
본 실시예에서는 혼합 생약 추출물의 염증성 장질환, 특히 궤양성 대장염에 대한 효능을 확인하였다. DSS 유도 염증성 장질환 모델은 사람의 궤양성 대장염과 유사한 형태학적 변화 및 증상을 나타내는 것으로 알려져 있다. 이에 따라 8주령 웅성 마우스(C57BL/6)를 일주일 이상 순화 사육한 후, Dextran Sulfate Sodium (DSS; 36,000-50,000 MW, MP Biomedicals, USA)를 투여하여 궤양성 대장염을 유발시켰다. 아무 처리도 하지 않은 정상군, DSS 및 증류수 투여군(음성대조군), DSS 및 5-Aminosalicylic Acid (5-ASA; Tokyo Chemical Industry Co., Japan) 투여군(양성대조군), 및 DSS 및 각 혼합 생약 추출물(황련, 형개, 백두옹, 한련초)를 투여한 군(실험군)으로 분류하여 실험을 수행하였다.In this example, the efficacy of the mixed herbal extract on inflammatory bowel disease, particularly 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, 8-week-old male mice (C57BL/6) were acclimated and bred for more than a week, and then Dextran Sulfate Sodium (DSS; 36,000-50,000 MW, MP Biomedicals, USA) was administered to induce ulcerative colitis. The normal group without any treatment, the DSS and distilled water administration group (negative control), the DSS and 5-Aminosalicylic Acid (5-ASA; Tokyo Chemical Industry Co., Japan) administration group (positive control), and DSS and each mixed herbal extract ( The experiment was conducted by classifying it into the group (experimental group) administered with Hwangryeon, Hyeonggae, Baekduong, and Hanryeoncho).
1-1. DAI 평가1-1. DAI evaluation
장질환은 일반적으로 체중 감소, 설사, 혈변 등의 임상증상을 통해 평가된다. 질병 활성 지수(Disease Activity Index; DAI)는 체중 감소율, 변 상태 및 출혈을 측정하여 각각에 점수를 부여하여 장질환의 정도를 분석하는 방법이다.Intestinal disease is generally evaluated through clinical symptoms such as weight loss, diarrhea, and bloody stool. The Disease Activity Index (DAI) is a method of analyzing the degree of bowel disease by measuring weight loss rate, stool condition, and bleeding, and assigning a score to each.
따라서 본 실시예에서는 체중 감소율, 변 상태 및 출혈을 측정하여 DAI를 분석하여 정상군, 대조군, 실험군을 비교하였다.Therefore, in this example, the weight loss rate, stool condition, and bleeding were measured and DAI was analyzed to compare the normal group, the control group, and the experimental group.
음수에 DSS를 희석하여 2.5 %로 제조한 후 상기 DSS 100 mL를 마우스에 급여하고 2일 간격으로 교체하여, 총 5일간 DSS를 급여하였다.After diluting DSS in negative water to make 2.5%, 100 mL of DSS was fed to mice and replaced every two days, and DSS was fed for a total of 5 days.
음성대조군은 증류수 0.4 mL을 실험 시작일로부터 14일 동안 1회/일 경구투여하였다.For the negative control group, 0.4 mL of distilled water was orally administered once/day for 14 days from the start of the experiment.
양성대조군은 음수에 희석한 5-ASA를 25 mg/kg의 용량으로 실험 시작일로부터 14일 동안 1회/일 경구투여하였다.The positive control group was orally administered 5-ASA diluted in negative water at a dose of 25 mg/kg once/day for 14 days from the start of the experiment.
실험군은 상기 제조예에서 제조한 각 생약 추출물을 표 2의 용량(mg/kg)으로 혼합 투여하였고, 실험 시작일로부터 14일간 1회/일 경구투여하였다.In the experimental group, each herbal extract prepared in Preparation Example was mixed and administered at the dose (mg/kg) shown in Table 2, and oral administration was performed once/day for 14 days from the start of the experiment.
실험 시작 후 매일 각 군의 마우스의 체중을 측정하여 체중 감소율로 계산하였으며, 변 상태 및 혈변 유무를 확인하였다. 상기 3가지 지표에 대해 하기 표 1의 기준에 따라 점수를 계산하였다.After the start of the experiment, the weight of each group of mice was measured every day, and the weight loss rate was calculated, and the stool state and the presence of bloody stool were checked. For the three indicators, scores were calculated according to the criteria in Table 1 below.
점수score 체중 감소율Weight loss rate 변 상태Stool state 출혈bleeding
00 < 1%<1% 정상normal 정상normal
1One 1-5%1-5% -- --
22 5-10%5-10% 항문 주위에 들러붙지 않는 묽은 변Loose stools that don't stick around the anus 약간의 출혈Slight bleeding
33 10-15%10-15% -- --
44 >15%>15% 항문 주위에 들러붙는 설사Diarrhea sticking around the anus 눈에 보이는 출혈Visible bleeding
표 1의 점수 계산 기준으로 계산한 합을 질병 활성 지수(Disease Activity Index; DAI)로 하기 표 2, 도 1에 나타내었다.The sum calculated based on the score calculation criterion in Table 1 is shown in Table 2 below as a Disease Activity Index (DAI).
연번 Serial number 대상(mg/kg) Target (mg/kg) 10일차 DAI 값 Day 10 DAI value
1One 정상군 Normal 0.00.0
22 음성대조군 Negative control 6.26.2
33 양성대조군 Positive control 4.04.0
44 황련50+형개5 Yellow Lotus 50+ Hyunggae 5 3.43.4
55 황련50+형개5+백두옹15 Hwangnyeon 50+ Hyunggae 5+ Baek Duong 15 2.02.0
66 황련50+형개5+백두옹50 Hwangnyeon 50+ Hyunggae 5+ Baek Duong 50 0.80.8
77 황련50+형개5+한련초15 Yellow Lotus 50 + Hyunggae 5 + Narcissus 15 0.20.2
음성대조군과 비교하여 모든 실험군에서 낮은 DAI 값을 나타내었으며, 양성대조군과 비교하더라도 낮은 DAI 값을 나타내었다. 특히 황련(50 mg/kg), 형개(5 mg/kg), 및 한련초(15 mg/kg)를 투여한 군(7번)은 DAI 값이 0.2로 가장 낮은 값을 나타내었고, 황련(50 mg/kg), 형개(5 mg/kg), 및 백두옹(50 mg/kg)를 투여한 군(6번)은 DAI 값이 0.8로 한련초(15 mg/kg)를 혼합하여 투여한 군(7번)에 이어 다음으로 낮은 값을 나타내었다.Compared with the negative control group, all experimental groups showed low DAI values, and even compared with the positive control group, the DAI values were low. In particular, the group administered Coptis (50 mg/kg), Hyeonggae (5 mg/kg), and Hanryeoncho (15 mg/kg) showed the lowest DAI value of 0.2, and Coptis (50 mg) /kg), Hyeonggae (5 mg/kg), and Baek Duong (50 mg/kg) were administered in the group (No. 6), and the DAI value was 0.8, and a mixture of Naryeoncho (15 mg/kg) was administered (No. 7). ) Followed by the next lower value.
1-2. 대장 길이의 측정1-2. Measurement of the length of the large intestine
장질환에서의 염증 반응은 대장 길이의 감소 정도로 평가될 수 있다. 이에 따라 본 실시예에서는 대장의 길이를 측정하여 정상군, 대조군, 실험군을 비교하였다.The inflammatory response in bowel disease can be assessed to the extent that the length of the large intestine is reduced. Accordingly, in this example, the length of the large intestine was measured to compare the normal group, the control group, and the experimental group.
실험 시작일로부터 14일 후에 표 3과 같이 투여군으로 분류된 마우스를 이산화탄소 가스로 희생시킨 뒤, 대장 부위를 제거하였다. 제거된 대장으로부터 대장의 길이를 측정하여 그 결과를 하기 표 3 및 도 2에 나타내었다.After 14 days from the start of the experiment, mice classified into the administration group as shown in Table 3 were sacrificed with carbon dioxide gas, and then the colon part was removed. The length of the large intestine was measured from the removed large intestine, and the results are shown in Table 3 and FIG. 2 below.
연번Serial number 대상(mg/kg)Target (mg/kg) 대장의 길이 (cm)Length of large intestine (cm)
1One 정상군 Normal 7.07.0
22 음성대조군 Negative control 4.64.6
33 양성대조군 Positive control 5.35.3
44 황련50+형개5 Yellow Lotus 50+ Hyunggae 5 5.75.7
55 황련50+형개5+백두옹15 Hwangnyeon 50+ Hyunggae 5+ Baek Duong 15 6.86.8
66 황련50+형개5+백두옹50 Hwangnyeon 50+ Hyunggae 5+ Baek Duong 50 6.66.6
77 황련50+형개5+한련초15 Yellow Lotus 50 + Hyunggae 5 + Narcissus 15 6.26.2
88 황련50+형개5+한련초50 Yellow Lotus 50 + Hyunggae 5 + Narcissus 50 6.76.7
황련(50 mg/kg) 및 형개(5 mg/kg) 혼합 추출물을 투여한 군(4번)에 비교하여 백두옹 또는 한련초 추출물을 추가하여 투여한 군(5 내지 8번)에서 정상군과 유사한 장길이 회복을 나타내었다.Compared to the group (No. 4) administered with Coptis Coptis (50 mg/kg) and Hyeonggae (5 mg/kg) mixed extract, in the group administered with Baekduong or Hanryeoncho extract added (No. 5 to No. 8), Janggil similar to that of the normal group It showed this recovery.
결국, DSS를 투여하여 염증성 장질환을 유발한 후 황련과 형개 생약 추출물에 백두옹 또는 한련초 추출물을 동시에 투여한 군에서, 음성대조군 대비 낮은 DAI 값을 나타내거나 장 길이가 정상군 수준으로 회복되어, 우수한 염증성 장질환 개선 또는 치료 효과를 나타냄을 확인하였다.In the end, after inducing inflammatory bowel disease by administering DSS, in the group where Baekduong or Hanryeoncho extract was simultaneously administered to the herbal medicine extract of Hyeonggae and Hyeonggae showed a lower DAI value compared to the negative control group or the intestine length was restored to the level of the normal group, it was excellent. It was confirmed that it showed an improvement or treatment effect for inflammatory bowel disease.
실험예 2: DNBS 유도 염증성 장질환 모델에서의 혼합 생약 추출물의 치료 효능Experimental Example 2: Treatment Efficacy of Mixed Herbal Extracts in DNBS-induced Inflammatory Bowel Disease Model
본 실시예에서는 혼합 생약 추출물의 염증성 장질환, 특히 크론병에 대한 효능을 확인하였다. DNBS 유도 염증성 장질환 모델은 T 세포 매개 면역반응을 유발하는 점에서 사람의 크론병과 밀접한 관련이 있는 것으로 알려져 있다. 이에 따라 8주령 웅성 마우스(C57BL/6)를 일주일 이상 순화 사육한 후, Dinitrobenzene sulfonic acid (DNBS; Sigma-Aldrich, USA)를 투여하여 염증성 장질환을 유발시켰다. 아무 처리도 하지 않은 정상군, DNBS 및 증류수 투여군(음성대조군), DNBS 및 각 혼합 생약 추출물(황련, 형개, 백두옹, 한련초)를 투여한 군(실험군)으로 분류하여 실험을 수행하였다.In this example, the efficacy of the mixed herbal extract on inflammatory bowel disease, particularly Crohn's disease, was confirmed. The DNBS-induced inflammatory bowel disease model is known to be closely related to Crohn's disease in humans in that it induces a T cell-mediated immune response. Accordingly, 8-week-old male mice (C57BL/6) were acclimated and bred for more than a week, and then dinitrobenzene sulfonic acid (DNBS; Sigma-Aldrich, USA) was administered to induce inflammatory bowel disease. The experiment was conducted by classifying into a normal group without any treatment, a group administered with DNBS and distilled water (negative control group), and a group administered with DNBS and each mixed herbal extract (Hwangryeon, Hyeonggae, Baekduong, Hanryeoncho) (experimental group).
2-1. 생존율 측정2-1. Measure survival rate
본 실시예에서는 DNBS만을 투여한 경우와, DNBS와 본 발명의 복합 생약 추출물을 투여한 경우의 생존율을 비교하였다.In this example, the survival rate was compared when DNBS was administered alone, and when DNBS and the complex herbal extract of the present invention were administered.
50% 에탄올 수용액에 DNBS를 용해시켜 40 mg/mL의 DNBS 용액을 제조하였다. 상기 제조된 DNBS 용액 0.1 mL를 카테터를 이용하여 마우스의 직장 내로 천천히 주입하였다.DNBS was dissolved in 50% ethanol aqueous solution to prepare a DNBS solution of 40 mg/mL. 0.1 mL of the prepared DNBS solution was slowly injected into the rectum of the mouse using a catheter.
음성대조군은 증류수 0.4 mL을 실험 시작일로부터 14일 동안 1회/일 경구투여하였다.For the negative control group, 0.4 mL of distilled water was orally administered once/day for 14 days from the start of the experiment.
또한, 실험군은 실험 시작일로부터 14일 동안 1회/일로 상기 제조예에서 제조한 각 생약 추출물을 표 4의 용량(mg/kg)으로 투여하였다.In addition, the experimental group was administered once/day for 14 days from the start of the experiment at the dose (mg/kg) of each herbal extract prepared in the above Preparation Example.
그 후, 각 군의 생존율을 측정하였고, 그 결과를 표 4 및 도 3에 나타내었다.Then, the survival rate of each group was measured, and the results are shown in Table 4 and FIG. 3.
연번Serial number 대상(mg/kg)Target (mg/kg) 생존율 (%)Survival rate (%)
1One 정상군 Normal 100.0100.0
22 음성대조군 Negative control 50.050.0
33 황련50+형개5+백두옹5 Hwangryun 50 + Hyunggae 5 + Baek Duong 5 66.766.7
44 황련50+형개5+백두옹15 Hwangnyeon 50+ Hyunggae 5+ Baek Duong 15 66.766.7
55 황련50+형개5+백두옹50 Hwangnyeon 50+ Hyunggae 5+ Baek Duong 50 100.0100.0
66 황련50+형개5+한련초5 Yellow Lotus 50 + Hyunggae 5 + Narcissus 5 83.383.3
77 황련50+형개5+한련초15 Yellow Lotus 50 + Hyunggae 5 + Narcissus 15 100.0100.0
음성대조군(2번)에서 확인할 수 있듯이 DNBS의 투여로 50%가 치사하였으나, 황련 및 형개의 혼합 추출물에 백두옹 또는 한련초의 생약 추출물을 혼합 투여한 군(3 내지 7번)은 모두 66.7% 이상의 생존율을 나타내었다.As can be seen in the negative control group (No. 2), 50% of the fatalities were killed by the administration of DNBS, but the group (No. 3 to No. 7) administered with the mixed extracts of Coptisaceae and Hyeonggai mixed with the herbal extracts of Baekduong or Hanryeoncho (No. Shown.
2-2. DAI 평가2-2. DAI evaluation
본 실시예에서는 DNBS로 유발된 염증성 장질환의 개선 여부를 질병 활성 지수(Disease Activity Index; DAI)로 평가하였다.In this example, the improvement of DNBS-induced inflammatory bowel disease was evaluated as a disease activity index (DAI).
마우스를 도 4에 나타낸 것과 같은 투여군으로 분류한 후, 각 시료를 투여하였다. 실험 시작 후 다음날 각 군의 마우스의 체중을 측정하여 체중 감소율로 계산하였으며, 변 상태 및 혈변 유무를 확인하였다. 상기 3가지 지표에 대해 실시예 1의 표 1의 기준에 따라 점수를 계산하여 DAI 값을 추산하였다.After the mice were classified into administration groups as shown in Fig. 4, each sample was administered. The next day after the start of the experiment, the weight of the mice in each group was measured and calculated as a weight loss rate, and the stool state and the presence of blood stool were checked. For the three indices, the DAI value was estimated by calculating the score according to the criteria in Table 1 of Example 1.
표 5 및 도 4에 나타낸 바와 같이, 황련 및 형개의 혼합 추출물에 백두옹(50 mg/kg) 또는 한련초(50 mg/kg)의 생약 추출물을 혼합 투여한 군(4번 및 7번)에서 정상군 수준의 DAI 값을 나타내었다.As shown in Table 5 and Figure 4, in the group (No. 4 and No. 7) in which the herbal extract of Baek Duong (50 mg/kg) or Hanryeoncho (50 mg/kg) was mixed and administered to the mixed extract of Coptis Coptisium and Hyeonggae The level of DAI value is shown.
연번Serial number 대상(mg/kg)Target (mg/kg) 1일차 DAI 값 Day 1 DAI value
1One 정상군 Normal 0.00.0
22 음성대조군 Negative control 2.72.7
33 황련50+형개5+백두옹5 Hwangryun 50 + Hyunggae 5 + Baek Duong 5 0.80.8
44 황련50+형개5+백두옹50 Hwangnyeon 50+ Hyunggae 5+ Baek Duong 50 0.30.3
55 황련50+형개5+한련초5 Yellow Lotus 50 + Hyunggae 5 + Narcissus 5 0.80.8
66 황련50+형개5+한련초15 Yellow Lotus 50 + Hyunggae 5 + Narcissus 15 0.70.7
77 황련50+형개5+한련초50 Yellow Lotus 50 + Hyunggae 5 + Narcissus 50 0.00.0
결국, 황련 및 형개 혼합 추출물에 백두옹 또는 한련초의 생약 추출물을 혼합 투여한 군에서 우수한 염증성 장질환 개선 또는 치료 효과를 갖는 것을 알 수 있다.As a result, it can be seen that the group in which the herbal extracts of Baekduong or Hanryeoncho were mixed and administered to the mixed extracts of Coptisaceae and Hyeonggae had excellent inflammatory bowel disease improvement or therapeutic effect.
이로써 복합 생약 추출물은 우수한 염증성 장질환 개선 또는 치료 효과를 나타냄을 확인하였다.Accordingly, it was confirmed that the complex herbal extracts exhibited excellent inflammatory bowel disease improvement or therapeutic effect.
실험예 3: DSS 유도 염증성 장질환 모델에서의 혼합 생약 추출물의 장벽 보호 효능Experimental Example 3: Barrier protection efficacy of mixed herbal extracts in a DSS-induced inflammatory bowel disease model
본 실시예에서는 혼합 생약 추출물의 염증성 장질환에서 장벽 보호 효능을 확인하였다. 8주령 웅성 마우스(C57BL/6)를 일주일 이상 순화 사육한 후, 아무 처리도 하지 않은 정상군, DSS 및 증류수 투여군(음성대조군), DSS 및 5-ASA 투여군(양성대조군), DSS 및 각 혼합 생약 추출물(황련, 형개, 백두옹, 한련초)을 투여한 군(실험군)으로 분류하여 실험을 수행하였다.In this example, the effect of protecting the barrier against inflammatory bowel disease of the mixed herbal medicine extract was confirmed. After acclimating 8-week-old male mice (C57BL/6) for more than a week, the normal group without any treatment, the DSS and distilled water administration group (negative control group), the DSS and 5-ASA administration group (positive control group), DSS and each mixed herbal medicine The experiment was conducted by classifying the extracts (Hwangnyeon, Hyeonggae, Baekduong, Hanryeoncho) into the group administered (experimental group).
음수에 DSS를 희석하여 2.5 %로 제조한 후 상기 DSS 100 mL를 마우스에 급여하고 2일 간격으로 교체하여, 총 6일간 DSS를 급여하였다.After diluting DSS in negative water to make 2.5%, 100 mL of DSS was fed to mice and replaced every two days, and DSS was fed for a total of 6 days.
음성대조군은 증류수 0.4 mL을 실험 시작일로부터 9일 동안 1회/일 경구투여하였다.For the negative control group, 0.4 mL of distilled water was orally administered once/day for 9 days from the start of the experiment.
양성대조군은 음수에 희석한 5-ASA를 25 mg/kg의 용량으로 실험 시작일로부터 9일 동안 1회/일 경구투여하였다.The positive control group was orally administered 5-ASA diluted in negative water at a dose of 25 mg/kg once/day for 9 days from the start of the experiment.
실험군의 경우 상기 제조예에서 제조한 각 생약 추출물을 표 6의 용량(mg/kg)으로 혼합 투여하였고, 실험 시작일로부터 9일 동안 1회/일 경구투여하였다.In the case of the experimental group, each herbal extract prepared in Preparation Example was mixed and administered at the dose (mg/kg) shown in Table 6, and was administered orally once/day for 9 days from the start of the experiment.
그 후 마우스에서 장 투과도를 측정하였다. DSS 유도 9일 차에 4시간 동안 절수, 절식시킨 마우스에 FITC-dextran(Sigma, USA)를 150 mg/ml 농도로 마리당 100 μl의 용량으로 경구 투여하였다. 3시간 이후 안와정맥얼기를 통해 채혈한 후 혈청만을 분리하여 형광을 측정하여, 그 결과를 표 6 및 도 5에 나타내었다.Thereafter, intestinal permeability was measured in mice. On the 9th day of DSS induction, FITC-dextran (Sigma, USA) was orally administered at a concentration of 150 mg/ml to 100 μl per head to the mice that were water-saved and fasted for 4 hours. After 3 hours, blood was collected through an orbital vein plexus, and only serum was separated to measure fluorescence, and the results are shown in Table 6 and FIG. 5.
연번Serial number 대상(mg/kg)Target (mg/kg) 형광 측정값 (음성대조군 대비)Fluorescence measurement value (compared to negative control)
1One 정상군Normal 0.220.22
22 음성대조군Negative control 1.001.00
33 양성대조군Positive control 0.680.68
44 황련50+형개5 Yellow Lotus 50+ Hyunggae 5 0.430.43
55 황련50+형개5+백두옹15 Hwangnyeon 50+ Hyunggae 5+ Baek Duong 15 0.290.29
66 황련50+형개5+한련초5 Yellow Lotus 50 + Hyunggae 5 + Narcissus 5 0.380.38
77 황련50+형개5+한련초50 Yellow Lotus 50 + Hyunggae 5 + Narcissus 50 0.260.26
황련과 형개 혼합 추출물에 백두옹(15 mg/kg) 또는 한련초(50 mg/kg)를 함께 투여한 군(5번 및 7번)은 정상군 수준의 형광 투과도 값을 나타내었다. 결국, 황련 및 형개 혼합 추출물과 비교하여 백두옹 또는 한련초의 동시 혼합 투여군의 장벽 보호 효과가 우수한 것을 알 수 있다.The group (No. 5 and No. 7) administered with Baek Duong (15 mg/kg) or Hanryeoncho (50 mg/kg) to the mixed extract of Coptis Coptisium and Hyeonggae showed the fluorescence transmittance values of the normal group. As a result, it can be seen that the barrier protection effect of the simultaneous mixed administration group of Baekduong or Hanryeoncho is superior compared to the mixed extract of Coptis Coptisium and Hyeonggae.
실험예 4: DSS 유도 염증성 장질환 모델에서의 단일 생약 추출물 및 혼합 생약 추출물의 치료 효능 비교Experimental Example 4: Comparison of the therapeutic efficacy of a single herbal extract and a mixed herbal extract in a DSS-induced inflammatory bowel disease model
본 실시예에서는 단일 생약 추출물과 혼합 생약 추출물의 DSS 유도 염증성 장질환 치료 효능을 비교 평가하였다. 8주령 웅성 마우스(C57BL/6)를 일주일 이상 순화 사육한 후, 아무 처리도 하지 않은 정상군, DSS 및 증류수 투여군(음성대조군), DSS 및 5-ASA 투여군(양성대조군), DSS 및 각 단일 생약 추출물 또는 혼합 생약 추출물(황련, 형개, 백두옹, 한련초)을 투여한 군(실험군)으로 분류하여 실험을 수행하였다.In this example, the efficacy of the treatment of DSS-induced inflammatory bowel disease was compared and evaluated between a single herbal extract and a mixed herbal extract. After acclimating 8-week-old male mice (C57BL/6) for more than a week, the normal group without any treatment, the DSS and distilled water administration group (negative control group), the DSS and 5-ASA administration group (positive control group), DSS and each single herbal medicine The experiment was performed by classifying the extract or mixed herbal extracts (Hwangryeon, Hyeonggae, Baekduong, Hanryeoncho) into a group administered (experimental group).
음수에 DSS를 희석하여 2.5%로 제조한 후 상기 DSS 100 mL를 마우스에 급여하고 2일 간격으로 교체하여, 총 6일간 DSS를 급여하였다.After diluting DSS in negative water to make 2.5%, 100 mL of DSS was fed to mice and replaced every two days, and DSS was fed for a total of 6 days.
음성대조군은 증류수 0.4 mL을 실험 시작일로부터 9일 동안 1회/일 경구투여하였다.For the negative control group, 0.4 mL of distilled water was orally administered once/day for 9 days from the start of the experiment.
양성대조군은 음수에 희석한 5-ASA를 25 mg/kg의 용량으로 실험 시작일로부터 9일 동안 1회/일 경구투여하였다.The positive control group was orally administered 5-ASA diluted in negative water at a dose of 25 mg/kg once/day for 9 days from the start of the experiment.
실험군의 경우 상기 제조예에서 제조한 각 생약 추출물을 표 7의 용량(mg/kg)으로 혼합 투여하였고, 실험 시작일로부터 9일 동안 1회/일 경구투여하였다.In the case of the experimental group, each herbal extract prepared in Preparation Example was mixed and administered at the dose (mg/kg) shown in Table 7, and it was administered orally once/day for 9 days from the start of the experiment.
4-1. DAI 평가4-1. DAI evaluation
실험 시작 후 매일 각 군의 마우스의 체중을 측정하여 체중 감소율로 계산하였으며, 변 상태 및 혈변 유무를 확인하였다. 상기 3가지 지표에 대해 상기 표 1의 기준에 따라 점수를 계산하였다. 표 1의 점수 계산 기준으로 계산한 합을 질병 활성 지수(Disease Activity Index; DAI)로 하기 표 7 및 도 6에 나타내었다.After the start of the experiment, the weight of each group of mice was measured every day, and the weight loss rate was calculated, and the stool state and the presence of bloody stool were checked. For the three indicators, scores were calculated according to the criteria in Table 1. The sum calculated based on the score calculation criteria in Table 1 is shown in Tables 7 and 6 below as the Disease Activity Index (DAI).
연번Serial number 대상(mg/kg)Target (mg/kg) 10일차 DAI 값 Day 10 DAI value
1One 정상군Normal 00
22 음성대조군Negative control 7.37.3
33 양성대조군Positive control 2.42.4
44 황련 100 Yellow lotus 100 22
55 형개 100 Hyunggae 100 2.42.4
66 한련초 100 Nasturtium 100 3.43.4
77 백두옹 100 Baek Duong 100 4.24.2
88 황련47.6+형개4.8+한련초47.6Hwangnyeon 47.6 + Hyunggae 4.8 + Hannyeoncho 47.6 1.61.6
99 황련47.6+형개4.8+백두옹47.6Yellow Lotus 47.6 + Hyunggae 4.8 + Baek Duong 47.6 1.81.8
음성대조군과 비교하여 모든 실험군에서 낮은 DAI 값을 나타내었다. 황련 및 형개 혼합 추출물에 한련초 또는 백두옹을 혼합하여 투여한 군(8번 및 9번)은 황련, 형개, 한련초, 또는 백두옹의 단일 생약 추출물 투여군(4 내지 7번)에 비해 낮은 DAI 값을 나타내었고, 양성대조군과 비교하더라도 낮은 DAI 값을 나타내었다.Compared to the negative control group, all experimental groups showed lower DAI values. The group administered by mixing Hanryeoncho or Baekduong to the mixed extract of Coptisaceae and Hyeonggae (No.8 and No.9) showed a lower DAI value compared to the group administered with a single herbal extract of Coptis Coptisium, Hyeonggae, Hanryeoncho, or Baekduong , Even compared with the positive control group, the DAI value was shown to be low.
4-2. 장 투과도 평가4-2. Intestinal permeability evaluation
마우스에서 장 투과도를 측정하였다. DSS 유도 9일 차에 4시간 동안 절수, 절식시킨 마우스에 FITC-dextran(Sigma, USA)를 150 mg/ml 농도로 마리당 100 μl의 용량으로 경구 투여하였다. 3시간 이후 안와정맥얼기를 통해 채혈한 후 혈청만을 분리하여 형광을 측정하였다. 그 결과를 표 8 및 도 7에 나타내었다.Intestinal permeability was measured in mice. On the 9th day of DSS induction, FITC-dextran (Sigma, USA) was orally administered at a concentration of 150 mg/ml to 100 μl per head to the mice that were water-saved and fasted for 4 hours. After 3 hours, blood was collected through an orbital vein plexus, and only serum was separated and fluorescence was measured. The results are shown in Table 8 and Fig. 7.
연번Serial number 대상(mg/kg)Target (mg/kg) 형광 측정값(음성대조군 대비)Fluorescence measurement value (compared to negative control)
1One 정상군Normal 0.220.22
22 음성대조군Negative control 1.001.00
33 양성대조군Positive control 0.680.68
44 황련100 Yellow Lotus 100 0.370.37
55 형개100Hyunggae100 0.480.48
66 한련초100 Nasturtium 100 0.550.55
77 백두옹100 Baek Duong 100 0.620.62
88 황련47.6+형개4.8+한련초47.6Hwangnyeon 47.6 + Hyunggae 4.8 + Hannyeoncho 47.6 0.260.26
99 황련47.6+형개4.8+백두옹47.6Yellow Lotus 47.6 + Hyunggae 4.8 + Baek Duong 47.6 0.290.29
황련 및 형개 혼합 추출물에 백두옹 또는 한련초를 혼합하여 투여한 군(8번 및 9번)은 정상군 수준의 형광 투과도 값을 나타내었다. 또한 황련, 형개, 한련초, 또는 백두옹의 개별 추출물(4 내지 7번)과 비교하여 황련 및 형개 혼합 추출물에 한련초 또는 백두옹을 함께 투여한 군(8번 및 9번)은 형광 투과도가 낮아서 장벽 보호 효과가 우수한 것을 알 수 있다.The group (No. 8 and No. 9) administered by mixing Baekduong or Hanryeoncho to the mixed extract of Hyeonggae and Hyeonggae showed the fluorescence transmittance values of the normal group. In addition, compared to the individual extracts of Coptis Rhizoma, Hyeonggae, Hannyeoncho, or Baekduong (No. 4 to 7), the group administered with Coptis Coptis or Baekduong (No. 8 and No. 9) to the mixed extract of C. It can be seen that is excellent.
4-3. 대장 길이의 측정4-3. Measurement of the length of the large intestine
또한, 실험 시작일로부터 10일 후에 마우스를 이산화탄소 가스로 희생시킨 뒤, 대장 부위를 제거하였다. 제거된 대장으로부터 대장의 길이를 측정하여 그 결과를 하기 표 9 및 도 8에 나타내었다.In addition, after the mice were sacrificed with carbon dioxide gas 10 days after the start of the experiment, the large intestine was removed. The length of the large intestine was measured from the removed large intestine, and the results are shown in Table 9 and FIG. 8 below.
연번Serial number 대상(mg/kg)Target (mg/kg) 대장의 길이 (cm)Length of large intestine (cm)
1One 정상군Normal 7.27.2
22 음성대조군Negative control 3.93.9
33 양성대조군Positive control 5.65.6
44 황련100 Yellow Lotus 100 6.16.1
55 형개100Hyunggae100 5.85.8
66 한련초100 Nasturtium 100 5.35.3
77 백두옹100 Baek Duong 100 5.45.4
88 황련47.6+형개4.8+한련초47.6Hwangnyeon 47.6 + Hyunggae 4.8 + Hannyeoncho 47.6 7.17.1
99 황련47.6+형개4.8+백두옹47.6Yellow Lotus 47.6 + Hyunggae 4.8 + Baek Duong 47.6 6.86.8
황련, 형개, 한련초, 또는 백두옹의 개별 추출물을 투여한 군(4번 내지 7번)에 비교하여 백두옹 또는 한련초 추출물을 혼합하여 투여한 군(8번 및 9번)에서 정상군과 유사한 장길이 회복을 나타내었다.Recovery of long length similar to that of the normal group in the group administered with a mixture of Baekduong or Hanryeoncho extract (No. 8 and No. 9) compared to the group administered with individual extracts of Hwangryeon, Hyeonggae, Hanryeoncho, or Baekduong (No. 4 to No. 7). Shown.
결국, DSS를 투여하여 염증성 장질환을 유발한 결과, 황련 및 형개 생약 추출물에 백두옹 또는 한련초 추출물을 혼합하여 투여한 군(8번 및 9번)에서, DAI 값이 유의미하게 개선되었으며, 장 길이 및 장벽 투과도 역시 정상군 수준으로 회복되었다. 따라서 황련, 형개 및 한련초 혼합 추출물과 황련, 형개 및 백두옹 혼합 추출물의 우수한 염증성 장질환 치료 효과를 확인하였다.Eventually, as a result of inducing inflammatory bowel disease by administering DSS, in the group (No. 8 and No. 9) administered by mixing Baekduong or Hanryeoncho extract with the herbal extracts of Hyeonggae and Hyeonggae, DAI values were significantly improved, and The barrier permeability was also restored to the level of the normal group. Therefore, it was confirmed that the mixed extract of Coptis Rhizoma, Hyeonggae and Hanryeoncho, and the mixed extract of Coptis Rhizoma, Hyeonggae and Baekduong were effective in treating inflammatory bowel disease.
하기에 본 발명의 추출물을 포함하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, an example of the formulation of the composition containing the extract of the present invention will be described, but the present invention is not intended to limit it, but is intended to be described in detail.
제제예Formulation example
제제예 1. 산제의 제조Formulation Example 1. Preparation of powder
제조예의 황련; 형개; 및 백두옹 또는 한련초 혼합 추출물 500 mgCoptis of a manufacturing example; Brotherhood; And Baekduong or nasturtium mixed extract 500 mg
유당 100 mg100 mg lactose
탈크 10 mg10 mg of talc
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight cloth to prepare a powder.
제제예 2. 정제의 제조Formulation Example 2. Preparation of tablets
제조예의 황련; 형개; 및 백두옹 또는 한련초 혼합 추출물 300 mgCoptis of a manufacturing example; Brotherhood; And Baekduong or nasturtium mixed extract 300 mg
옥수수전분 100 mg100 mg corn starch
유당 100 mg100 mg lactose
스테아린산 마그네슘 2 mg2 mg of magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above ingredients, tablets are prepared by tableting according to a conventional tablet manufacturing method.
제제예 3. 캅셀제의 제조 Formulation Example 3. Preparation of Capsule
제조예의 황련; 형개; 및 백두옹 또는 한련초 혼합 추출물 200 mgCoptis of a manufacturing example; Brotherhood; And Baekduong or nasturtium mixed extract 200 mg
결정성 셀룰로오스 3 mg3 mg of crystalline cellulose
락토오스 14.8 mg14.8 mg lactose
마그네슘 스테아레이트 0.2 mgMagnesium stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare a capsule.
제제예 4. 액제의 제조Formulation Example 4. Preparation of liquid formulation
제조예의 황련; 형개; 및 백두옹 또는 한련초 혼합 추출물 4 gCoptis of a manufacturing example; Brotherhood; And Baekduong or nasturtium mixed extract 4g
이성화당 10 g10 g of isomerized sugar
만니톨 5 g5 g of mannitol
정제수 적량Purified water appropriate amount
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100 ml로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.According to the usual preparation method of the liquid formulation, add and dissolve each component in purified water, add an appropriate amount of lemon flavor, mix the above ingredients, add purified water, add purified water, adjust the total to 100 ml, and fill in a brown bottle. It is sterilized to prepare a liquid formulation.
제제예 5. 건강 식품의 제조Formulation Example 5. Manufacture of health food
제조예의 황련; 형개; 및 백두옹 또는 한련초 혼합 추출물 1,000 mgCoptis of a manufacturing example; Brotherhood; And Baekduong or nasturtium mixed extract 1,000 mg
비타민 혼합물 적량The right amount of vitamin mixture
비타민 A 아세테이트 70 ㎍Vitamin A acetate 70 ㎍
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎Vitamin B1 0.13 mg
비타민 B2 0.15 ㎎Vitamin B2 0.15 mg
비타민 B6 0.5 ㎎Vitamin B6 0.5 mg
비타민 B12 0.2 ㎍Vitamin B12 0.2 ㎍
비타민 C 10 ㎎ Vitamin C 10 mg
비오틴 10 ㎍Biotin 10 ㎍
니코틴산아미드 1.7 ㎎Nicotinic acid amide 1.7 mg
엽산 50 ㎍ Folic acid 50 ㎍
판토텐산 칼슘 0.5 ㎎0.5 mg of calcium pantothenate
무기질 혼합물 적량Suitable amount of inorganic mixture
황산제1철 1.75 ㎎Ferrous sulfate 1.75 mg
산화아연 0.82 ㎎Zinc oxide 0.82 mg
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎Potassium monophosphate 15 mg
제2인산칼슘 55 ㎎Dicalcium phosphate 55 mg
구연산칼륨 90 ㎎Potassium citrate 90 mg
탄산칼슘 100 ㎎100 mg of calcium carbonate
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.The 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 for preparing a health food composition according to a conventional method.
제제예 6. 건강 음료의 제조Formulation Example 6. Preparation of healthy beverage
제조예의 황련; 형개; 및 백두옹 또는 한련초 혼합 추출물 1,000 mgCoptis of a manufacturing example; Brotherhood; And Baekduong or nasturtium mixed extract 1,000 mg
구연산 1,000 ㎎Citric acid 1,000 mg
올리고당 100 g100 g oligosaccharides
매실농축액 2 g2 g of plum concentrate
타우린 1 g1 g taurine
정제수를 가하여 전체 900 ㎖Total 900 ml by adding purified water
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85 ℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 L 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다.After mixing the above ingredients according to a normal health drink manufacturing method, stirring and heating at 85°C for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized, and stored in a refrigerator. It is used in the manufacture of the health beverage composition of the invention.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.The 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.

Claims (10)

  1. 황련; 형개; 및 한련초 또는 백두옹의 생약 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 치료용 약제학적 조성물.goldthread; Brotherhood; And a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease comprising the herbal extract of nasturtium or baekduong as an active ingredient.
  2. 제1항에 있어서, 상기 생약 추출물은 물, C1 내지 C6의 알코올, 아세트산 및 이들의 혼합 용매로 이루어지는 군으로부터 선택되는 용매로 추출된 것인, 염증성 장질환의 예방 또는 치료용 약제학적 조성물.The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the herbal extract is extracted with a solvent selected from the group consisting of water, C1 to C6 alcohol, acetic acid, and a mixed solvent thereof.
  3. 제1항에 있어서, 상기 생약 추출물은 0.01% 내지 90% 에탄올 추출물인 것인, 염증성 장질환의 예방 또는 치료용 약제학적 조성물.The pharmaceutical composition according to claim 1, wherein the herbal extract is 0.01% to 90% ethanol extract.
  4. 제1항에 있어서, 상기 생약 추출물은 60% 내지 80% 에탄올 추출물인 것인, 염증성 장질환의 예방 또는 치료용 약제학적 조성물.The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the herbal extract is 60% to 80% ethanol extract.
  5. 제1항에 있어서, 상기 염증성 장질환은 크론병, 궤양성 대장염, 장형 베체트병, 장결핵, 출혈성 직장 궤양, 불확정 대장염(indeterminate colitis), 세균성 장염, 바이러스성 장염, 아메바성 장염 및 허혈성 대장염으로 이루어진 군으로부터 선택되는 질환인 것인, 염증성 장질환의 예방 또는 치료용 약제학적 조성물.The method of claim 1, wherein 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 colitis. That is a disease selected from the group, a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease.
  6. 제1항에 있어서, 상기 염증성 장질환은 크론병 또는 궤양성 대장염인 것인, 염증성 장질환의 예방 또는 치료용 약제학적 조성물.The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.
  7. 제1항에 있어서, 상기 생약 추출물은 황련; 형개; 및 한련초 또는 백두옹이 0.05-20 : 0.05-20 : 0.05-20 중량비로 혼합된 것인, 염증성 장질환의 예방 또는 치료용 약제학적 조성물.The method of claim 1, wherein the herbal extract is Coptis Coptis; Brotherhood; And Naryeoncho or Baekduongi 0.05-20: 0.05-20: 0.05-20 will be mixed in a weight ratio, a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease.
  8. 제1항에 있어서, 상기 생약 추출물은 황련; 형개; 및 한련초 또는 백두옹이 10 : 1 : 1-10 중량비로 혼합된 것인, 염증성 장질환의 예방 또는 치료용 약제학적 조성물.The method of claim 1, wherein the herbal extract is Coptis Coptis; Brotherhood; And Naryeoncho or Baekduongi 10:1: 1 to 10, which is mixed in a weight ratio, a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease.
  9. 황련; 형개; 및 한련초 또는 백두옹의 생약 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 개선용 식품 조성물.goldthread; Brotherhood; And a food composition for preventing or improving inflammatory bowel disease, comprising the herbal extract of nasturtium or baekduong as an active ingredient.
  10. 황련; 형개; 및 한련초 또는 백두옹의 생약 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 개선용 사료 조성물.goldthread; Brotherhood; And a feed composition for the prevention or improvement of inflammatory bowel disease comprising the herbal extract of nasturtium or baekduong as an active ingredient.
PCT/KR2020/013713 2019-10-10 2020-10-08 Composition for preventing or treating inflammatory bowel disease comprising extracts of complex herbal medicines WO2021071269A1 (en)

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