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WO2024043728A1 - Composition contenant cnidium monnieri pour la prévention ou le traitement de la gastrite et de l'ulcère gastrique - Google Patents

Composition contenant cnidium monnieri pour la prévention ou le traitement de la gastrite et de l'ulcère gastrique Download PDF

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Publication number
WO2024043728A1
WO2024043728A1 PCT/KR2023/012587 KR2023012587W WO2024043728A1 WO 2024043728 A1 WO2024043728 A1 WO 2024043728A1 KR 2023012587 W KR2023012587 W KR 2023012587W WO 2024043728 A1 WO2024043728 A1 WO 2024043728A1
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Prior art keywords
gastritis
extract
gastric
bee
present
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Ceased
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PCT/KR2023/012587
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English (en)
Korean (ko)
Inventor
김영식
김용빈
이서인
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Woosuk University
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Woosuk University
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Publication of WO2024043728A1 publication Critical patent/WO2024043728A1/fr
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/234—Cnidium (snowparsley)
    • 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
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • 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

Definitions

  • the present invention relates to a composition for preventing, ameliorating or treating gastritis and gastric ulcers containing bee dead extract as an active ingredient.
  • the stomach is a sac-shaped digestive organ that temporarily stores and digests food sent from the mouth through the esophagus. It is located in the upper left part of the abdomen, below the left ribs, and is connected to the esophagus above and the duodenum below. there is.
  • the stomach wall is composed of the mucosa layer, submucosa layer, muscle layer, and serosa layer, and blood vessels and nerves are located in the submucosa layer.
  • the stomach is governed by the autonomic nerve, and when the sympathetic nerve is stimulated, it inhibits peristalsis of the stomach and reduces gastric juice secretion. Additionally, when food enters the stomach, it secretes gastric acid, a strongly acidic liquid, to digest it. At this time, the gastric mucosal protective layer secretes mucus to protect the stomach wall cells from gastric acid.
  • gastric mucosa protective layer that protects the stomach is easily damaged by attack from various types of aggressive agents.
  • Representative examples include various internal and external factors such as smoking, stress, medications, Helicobacter pylori infection, alcohol, non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and indomethacin.
  • NSAIDs non-steroidal anti-inflammatory drugs
  • the secretion of gastric mucus is not smooth or When there is a problem with excessive stomach acid, the stomach lining can be damaged, causing inflammation and ulcers.
  • Gastritis and gastric ulcers can be said to be the most common digestive system diseases suffered by 1 in 9 Koreans, and are also common enough to rank as the 8th most common disease in Korea as of 2020.
  • the annual medical expenses spent on treating the two diseases are known to amount to 367.7 billion won.
  • Gastritis and gastric ulcers are divided into acute and chronic.
  • symptoms such as sudden pain in the solar plexus area, nausea, and vomiting may appear.
  • chronic cases there may be no symptoms, and pain in the upper abdomen such as indigestion, abdominal bloating, vomiting, and heartburn may occur.
  • digestive disorders are increasing due to stress-related gastrointestinal disorders, such as gastritis and increased gastric tension.
  • the number of patients with gastritis or gastric ulcers is expected to continue to increase due to the continuous consumption of spicy foods, fatty foods, cigarettes, and alcohol. It is expected.
  • NSAIDs non-steroidal anti-inflammatory drugs
  • Indomethacin is one of the non-steroidal anti-inflammatory drugs (NSAIDs) commonly used as prescription drugs to reduce fever, pain, stiffness, and swelling caused by inflammation. It is a drug that works by inhibiting the production of endogenous signaling molecules. Specifically, it works by inhibiting cyclooxygenase, an enzyme that acts as a catalyst for prostaglandin production.
  • cyclooxygenase an enzyme that acts as a catalyst for prostaglandin production.
  • the production process of prostaglandin which regulates the regeneration and function of the gastrointestinal mucosal cell layer, is blocked by indomethacin, the gastric mucosa is damaged and ulcers are prone to occur.
  • PPIs proton pump inhibitors
  • H2 receptor antagonists H2 receptor antagonists
  • the most widely used PPIs include omeprazole and lansoprazol, and exert their medicinal effect by strongly inhibiting the secretion of gastric acid by irreversibly binding to the proton pump present in the gastric wall cells.
  • Omeprazole is a drug used for peptic ulcer disease, indigestion, and gastroesophageal reflux disease. It prevents gastric acid from being secreted by irreversibly binding to the proton pump present in the parietal cells of the stomach.
  • PPIs have the disadvantage of causing side effects such as proliferation of gastric acid-secreting cells, gland cysts, hypergastrinemia, and fundic gland polyps when administered (Jalving M, Koomrnstra JJ, et al., Alimentary Pharmacology and Therapeutics, 2006; Raghunath AS, O'Morain C et al., Alimentary Pharmacology and Therapeutics, 2006; Stolte M, Gastroenterology, 1993).
  • PPIs proton pump inhibitors
  • the purpose of the present invention is to provide a pharmaceutical composition for preventing or treating gastritis and gastric ulcers containing bee dead extract as an active ingredient.
  • Another object of the present invention is to provide a food composition for preventing or ameliorating gastritis and gastric ulcers containing bee dead extract as an active ingredient.
  • Another object of the present invention is to provide a method for preventing or treating gastritis and gastric ulcers, including the step of administering bee casualty extract to an individual in need thereof.
  • Another object of the present invention is to provide a use of the bee killer extract for preventing or treating gastritis and gastric ulcers.
  • Another object of the present invention is to provide the use of the extract of the bee dead box for use in the manufacture of a medicament for use in the prevention or treatment of gastritis and gastric ulcers.
  • the present invention provides a pharmaceutical composition for preventing or treating gastritis and gastric ulcers, which contains an extract of Cnidium monnieri as an active ingredient.
  • ' Cnidium monnieri ' is a biennial herb belonging to the Umbrella family. It mainly grows in sunny, well-drained mountain areas, moist field edges, and riverside grasslands, and white flowers bloom in August.
  • Oriental medicine it is known to have spicy and warm properties that drive away cold energy and restore health (Hwang, EI, Lee, SK, So, SH, Koo, BS, Han, GH and Kim, NM (2007) Isolation and development of quantitative determination of Torilin from the Torilis Fructus. Kor. J. Pharmacogn).
  • bee casualties can be used without limitation, whether those growing naturally, purchased or cultivated, and include all parts such as outgrowth, above-ground parts, leaves, roots, stems, flowers, fruits, and seeds, without limitation. Specifically, its whole shoots, aerial parts, leaves, or fruits can be used.
  • the bee casualties include those in their natural state as well as those that have been processed such as semi-dried, dried, fermented or steamed.
  • extract refers to an active ingredient isolated from a natural product, that is, a substance showing the desired activity.
  • the extract can be obtained through an extraction process using water, an organic solvent, or a mixed solvent thereof.
  • the extract, crude extract, purified product, dried powder or concentrate thereof, or any product formulated using the same It can be comprehensively interpreted in terms of form.
  • the extract includes fractionation of the extract that has gone through the extraction process or extract that has gone through a conventional purification process, and can also be produced in powder form by additional processes such as reduced pressure distillation, freeze-drying, spray drying, etc.
  • the extract of the present invention can be extracted according to methods commonly used in the art, such as immersion (cold immersion, warm immersion) extraction, heat extraction, ultrasonic extraction, hot water extraction, reflux extraction, supercritical extraction, or using organic solvents. And, according to one embodiment of the present invention, it may be a reflux extraction method, but is not limited thereto.
  • the extract of the present invention may be extracted with water or an organic solvent, and specifically, water, alcohol, glycerin, butylene glycol, propylene glycol, methyl acetate, ethyl acetate, acetone, benzene, hexane, diethyl ether, and It may be extracted with one or more solvents selected from the group consisting of dichloromethane, more specifically water or a C 1 to C 4 lower alcohol, more specifically water, ethanol, methanol or a mixed solvent thereof, and is an aspect of the present invention.
  • the extraction solvent may be ethanol, but is not limited thereto.
  • the extraction solvent of the present invention can be used in an amount of 1 to 50 times, specifically 1 to 30 times, and more specifically 1 to 15 times, based on the weight of the sample, but is not limited thereto.
  • the extraction temperature of the extract of the present invention may be 50 to 100 °C, specifically 75 to 95 °C, and the extraction time may be 1 to 10 hours, specifically 1 to 5 hours, and according to one embodiment of the present invention, 2 It may be, but is not limited to, time. Additionally, the number of extractions of the extract of the present invention may be 1 to 5 times, specifically 1 to 3 times.
  • the extract liquid that has undergone the above extraction process may then be further subjected to fractionation with a solvent selected from the group consisting of hexane, methylene chloride, acetone, ethyl acetate, chloroform, or mixtures thereof.
  • a solvent selected from the group consisting of hexane, methylene chloride, acetone, ethyl acetate, chloroform, or mixtures thereof.
  • two or more solvents can be used individually or in combination, and fractions of each solvent can be prepared by using them sequentially depending on the polarity of the solvent.
  • the extract or the fraction obtained from the above-mentioned extraction process can then be filtered, concentrated, or dried to remove the solvent, and all of filtration, concentration, and drying can be performed.
  • the filtration may be performed using filter paper or a vacuum filter, and the concentration may be performed using a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto.
  • the drying may be performed, for example, by freeze drying, spray drying, boiling drying, or reduced pressure drying. According to one embodiment of the present invention, it may be freeze drying, but is not limited thereto.
  • Gastric ulcer refers to a defect in the gastric mucosa caused by attack by stomach acid and pepsin, and refers to a case where the defect of the histologically necrotic mucosa extends to the submucosal layer or lower.
  • gastritis and gastric ulcer include gastritis and gastric ulcer caused by alcohol or NSAID.
  • the bee casualty extract showed a significant effect of reducing bleeding and lesion area, and from this, the bee casualty extract showed an excellent effect on gastritis and gastric ulcers. was confirmed.
  • gastritis and gastric ulcer may include both acute or chronic gastritis and gastric ulcer.
  • the composition of the present invention protects the gastric mucosa against acute gastritis and gastric ulcers caused by excessive drinking, taking NSAIDs, etc., and suppresses bleeding and lesions in the stomach lining, thereby preventing not only acute gastritis and gastric ulcers but also chronic symptoms that persist. It has significant preventive and therapeutic effects on gastritis and gastric ulcers.
  • the pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, excipient, or diluent in addition to the bee dead extract as an active ingredient.
  • the carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, Examples include, but are not limited to, polyvinyl pyrrolidone, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
  • the pharmaceutical composition of the present invention can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, or sterile injection solutions according to conventional methods. .
  • oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, or sterile injection solutions according to conventional methods.
  • it can be prepared using commonly used diluents or excipients such as fillers, weighting agents, binders, wetting agents, disintegrants, and surfactants.
  • Solid preparations for oral administration include, but are not limited to, tablets, pills, powders, granules, capsules, etc.
  • solid preparations may be prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc. Additionally, in addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.
  • excipients such as wetting agents, sweeteners, fragrances, and preservatives.
  • Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations and suppositories.
  • Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.
  • injectable esters such as ethyl oleate.
  • Withepsol, Macrogol, Tween 61, cacao, laurin, glycerogelatin, etc. can be used as a base for suppositories.
  • the pharmaceutical composition of the present invention can be administered orally or parenterally according to the desired method.
  • parenteral administration it can be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc., specifically.
  • the composition of the present invention can be administered orally.
  • the pharmaceutical composition according to the present invention can be administered in a pharmaceutically effective amount, that is, an amount sufficient to prevent and treat diseases with a reasonable benefit/risk ratio applicable to medical prevention or treatment.
  • a pharmaceutically effective amount that is, an amount sufficient to prevent and treat diseases with a reasonable benefit/risk ratio applicable to medical prevention or treatment.
  • the dosage of the active ingredient varies depending on the patient's condition and weight, drug form, administration route and period, type of disease, and other factors well known in the medical field, including the composition of the present invention and the combination and concomitant drugs used, but will be determined by those skilled in the art. can be appropriately selected.
  • composition of the present invention can be used alone or in combination with methods using surgery, hormone therapy, chemotherapy, and biochemical reaction regulators to prevent or treat gastritis and gastric ulcers.
  • the present invention provides a food composition for preventing or improving gastritis and gastric ulcers containing bee dead box extract as an active ingredient.
  • improvement means improving the clinical or pathological condition of a patient compared to before administration of the composition.
  • the food composition of the present invention can be added as is or used with other foods or food ingredients, and can be used appropriately according to conventional methods.
  • the food composition of the present invention contains bee dead extract as an active ingredient, and the content of the active ingredient can be appropriately determined depending on the purpose of use (prevention, improvement or therapeutic treatment).
  • bee dead box extract can be added in an amount of 0.0001 to 100% by weight based on the total weight of the food.
  • the type of food there is no particular limitation on the type of food, and all foods in the conventional sense are included.
  • foods to which the composition of the present invention can be added include meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, and beverages. , tea, drinks, alcoholic beverages and vitamin complexes, etc.
  • the food composition of the present invention may be a functional food, and specifically may be a health functional food, depending on the purpose of the present invention.
  • the functional food refers to a food that emphasizes the bioregulatory function of food and adds added value to act and express for a specific purpose using physical, biochemical, and biotechnological methods.
  • the ingredients of these functional foods are designed and processed to fully exert the body's regulatory functions related to biological defense, regulation of body rhythm, prevention and recovery of disease, and are used as food additives, sweeteners or functional raw materials that are acceptable as food. It may contain.
  • the above-mentioned health functional foods refer to foods manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and pills using raw materials or ingredients with functional properties useful to the human body.
  • the amount of bee dead box extract added in the health functional food according to the present invention cannot be uniformly defined depending on the type of health functional food being targeted, but it can be added within the range that does not damage the original taste of the food, and is usually used for the target food. It may range from 0.01 to 70% by weight, specifically 0.1 to 50% by weight. In addition, in the case of health functional foods in the form of pills, granules, tablets or capsules, it can be added in the range of usually 0.1 to 100% by weight, specifically 0.5 to 80% by weight. According to one embodiment of the present invention, the health functional food of the present invention may be in the form of a pill, tablet, capsule, or beverage.
  • the food composition of the present invention may contain common food additives, and its suitability as a food additive is determined by the specifications for the relevant item in accordance with the general provisions of the Food Additive Code and General Test Methods approved by the Food and Drug Safety Administration, unless otherwise specified. and standards.
  • the extract of the present invention When the extract of the present invention is added to food, various nutrients, vitamins, flavors, colorants, pactic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, It can be added together with auxiliary ingredients such as alcohol.
  • the present invention provides a method for preventing or treating gastritis and gastric ulcers comprising administering a bee dead extract to a subject in need thereof.
  • the present invention provides the use of said bee dead extract for the prevention or treatment of gastritis and gastric ulcers.
  • the invention provides the use of said extract of bee cassava for the manufacture of a medicament for use in the prevention or treatment of gastritis and gastric ulcers.
  • the bee casualty extract of the present invention can be usefully used in the prevention and treatment of gastritis and gastric ulcers.
  • by administering the bee casualty extract to alcoholic gastritis and gastrointestinal tract damage caused by NSAIDs it reduces bleeding in the stomach lining and reduces lesions, thereby treating gastritis. and can have a significant effect on gastric ulcers.
  • Figure 1 shows a photograph of the stomach lining comparing the bleeding area of the stomach lining according to bee dead extract or omeprazole treatment in an alcohol-induced gastritis/gastric lesion animal model.
  • Figure 2 is a graph comparing the bleeding area of the stomach lining according to treatment with bee dead extract or omeprazole in an alcohol-induced gastritis/gastric lesion animal model.
  • Figure 3 shows a photograph of the stomach lining comparing the bleeding area according to treatment with bee dead extract or omeprazole in an indomethacin-induced gastritis/gastric lesion animal model.
  • Figure 4 is a graph comparing the bleeding area according to treatment with bee dead extract or omeprazole in an indomethacin-induced gastritis and gastric lesion animal model.
  • omeprazole a clinically widely used proton pump inhibitor
  • the experimental group was administered the bee dead box extract prepared in the above Preparation Example dissolved in primary distilled water at a concentration of 300 mg/kg and in a volume of 1.0 mL per 100 g of rat body weight. 30 minutes after drug administration, 1.0 mL of 100% ethanol was orally administered to all experimental groups.
  • the bee casualty extract of the present invention is significantly effective in preventing and treating gastritis and gastric ulcers, and is especially effective in acute gastritis or gastric ulcers caused by alcohol, etc.
  • omeprazole was orally administered to the rats at a concentration of 20 mg/kg and a volume of 1.0 mL per 100 g of rat body weight.
  • the experimental group was administered the bee dead box extract prepared in the above Preparation Example dissolved in primary distilled water at a concentration of 300 mg/kg and a volume of 1.0 mL per 100 g of rat body weight.
  • indomethacin dissolved in 5% sodium bicarbonate solution was orally administered at a concentration of 100 mg/kg and a volume of 1.0 mL per 100 g of rat body weight.
  • the bee casualty extract of the present invention has a significant effect in preventing and treating gastritis and gastric ulcers, and in particular, has a significant effect on acute gastritis or gastric ulcers caused by indomethacin, etc.

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Abstract

La présente invention concerne une composition pharmaceutique contenant un extrait de Cnidium monnieri pour la prévention ou le traitement de la gastrite et de l'ulcère gastrique, et une composition alimentaire pour la prévention ou le soulagement de la gastrite et de l'ulcère gastrique, la composition présentant des effets remarquables sur la gastrite et l'ulcère gastrique, tels que la suppression d'hémorragie et de lésions dans la paroi interne de l'estomac et des dommages à un tractus gastro-intestinal provoqué par l'alcool, les AINS, etc.
PCT/KR2023/012587 2022-08-25 2023-08-24 Composition contenant cnidium monnieri pour la prévention ou le traitement de la gastrite et de l'ulcère gastrique Ceased WO2024043728A1 (fr)

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KR1020220106674A KR102666751B1 (ko) 2022-08-25 2022-08-25 벌사상자 추출물을 포함하는 위염 및 위궤양의 예방 또는 치료용 조성물
KR10-2022-0106674 2022-08-25

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KR20110036317A (ko) * 2009-10-01 2011-04-07 재단법인 제주테크노파크 항염증성 조성물
KR20140119417A (ko) * 2013-04-01 2014-10-10 원광대학교산학협력단 벌사상자 추출물을 유효성분으로 함유하는 면역증강 및 암질환 치료 또는 예방용 조성물
KR20210112570A (ko) * 2020-03-05 2021-09-15 남종현 항 전염성 위장염 바이러스(tgev)용 조성물 및 이를 포함하는 약학 조성물

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KR20030095540A (ko) * 2002-06-12 2003-12-24 주식회사 뉴로넥스 감초, 강황 및 소엽의 추출물을 함유한 위염 및 위궤양의예방 및 치료를 위한 조성물
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KR20140119417A (ko) * 2013-04-01 2014-10-10 원광대학교산학협력단 벌사상자 추출물을 유효성분으로 함유하는 면역증강 및 암질환 치료 또는 예방용 조성물
KR20210112570A (ko) * 2020-03-05 2021-09-15 남종현 항 전염성 위장염 바이러스(tgev)용 조성물 및 이를 포함하는 약학 조성물

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FAN HUAYING; GAO ZHENFANG; JI KAI; LI XIN; WU JINGBAO; LIU YUE; WANG XUEKAI; LIANG HAIYUE; LIU YANAN; LI XIAOTING; LIU PAN; CHEN D: "The in vitro and in vivoanti-inflammatory effect of osthole, the major natural coumarin from Cnidium monnieri(L.) Cuss, via the blocking of the activation of the NF-κB and MAPK/p38 pathways", PHYTOMEDICINE, ELSEVIER, AMSTERDAM, NL, vol. 58, 1 January 1900 (1900-01-01), AMSTERDAM, NL , XP085683879, ISSN: 0944-7113, DOI: 10.1016/j.phymed.2019.152864 *

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