WO2013187576A1 - Composition comprenant de la silymarine en tant que principe actif pour la prévention et le traitement d'ulcères peptiques provoqués par la consommation d'alcool - Google Patents

Composition comprenant de la silymarine en tant que principe actif pour la prévention et le traitement d'ulcères peptiques provoqués par la consommation d'alcool Download PDF

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Publication number
WO2013187576A1
WO2013187576A1 PCT/KR2013/001377 KR2013001377W WO2013187576A1 WO 2013187576 A1 WO2013187576 A1 WO 2013187576A1 KR 2013001377 W KR2013001377 W KR 2013001377W WO 2013187576 A1 WO2013187576 A1 WO 2013187576A1
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Prior art keywords
silymarin
gastric
pharmaceutically acceptable
acceptable salt
gastric ulcer
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PCT/KR2013/001377
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English (en)
Korean (ko)
Inventor
강종순
신정휴
이창우
김형진
오수진
윤지은
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한국생명공학연구원
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Publication of WO2013187576A1 publication Critical patent/WO2013187576A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • 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
    • 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
    • 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

Definitions

  • Alcoholic gastric ulcer prevention and treatment composition comprising silymarin as an active ingredient
  • the present invention relates to a composition for preventing and treating alcoholic gastric ulcer, comprising silymarin (Silymarin) or a pharmaceutically acceptable salt thereof as an active ingredient.
  • Silymarin is a flavonoid compound derived from S // y /? Marianu, a fruit belonging to the Asteraceae family, and silymarin is si lybin, silidianin, and sily icristin. It consists of three main components, and contains a variety of flavonoids such as dehydrosilybin.
  • the plant is native to Southern Europe and North Africa, but later settled in the Americas and is now grown for ornamental and medicinal purposes. Thistle is a plant known from the milk mothers to drink milk thistle tea in order to make it milk well. Also, a German natural therapist Rademarker has shown that thistle has excellent effects on liver and gallbladder disease and jaundice. Discovered and began to become more famous after that.
  • pylori is a gastric mucosa Gram-negative bacillus inhabiting epithelial intercellular junctions, the optimum pH is 7.07.4 and grows in an aerobic condition of 3037. When these conditions are not stratified or environmental changes occur, changes in the form of coccoids are observed. do. Its pathogenic factors include strong urease production, which is the most representative feature, and flagella, which allows adhesion and migration to the gastric mucosa layer, as well as Vag A, Cag A, and lipopolysaccharad ( Cytotoxins, including lipopolysaccharides, have been studied.
  • Alcoholic gastric ulcer is one of the essential diseases in modern people. People are going through. In particular, in addition to social stress, frequent intake of alcohol is accompanied by severe gastric ulcers and liver disease, and many medicines and functional foods are being sold to improve this. In other words, efforts are being made to lower alcohol blood levels by activating ADH and ALDH. However, there are few effective substances that show significant detoxification effects by activating enzymes in a short period of time.
  • a gastric ulcer therapeutic agent such as pantoprazole, which is a hydrogen ion pump inhibitor, is effective for gastric ulcers caused by other causes, but is less effective in alcoholic gastric ulcers.
  • Known therapeutic agents for gastric ulcers include hydrogen transfer pump inhibitors that block acid secretion from wall cells, antacids, histamine receptors for promoting acid secretion (H2-ant agonists), and mucin layer enhancers (PGs) Derivatives and antibiotics that can eradicate Helicobacter pylori are typical.
  • silymarin can be used to treat alcoholic gastric ulcers. Accordingly, the present inventors confirmed that treatment with silymarin or its pharmaceutically acceptable salts is effective in reducing the gastric injury area of the ethanol-induced gastric ulcer model animal, improving gastric mucus volume, and is involved in the NP-SH part as a result of NEM pretreatment.
  • the present invention was completed by revealing that the amount of NP-SH is recovered, and that the effect of inhibiting gastric ulceration after N-NAME pretreatment is reduced, thereby being useful for preventing or treating the gastric ulcer caused by excessive drinking. It was.
  • the present invention provides a pharmaceutical composition for the prevention and treatment of gastric injury, gastric ulcer or gastrointestinal disease induced by alcohol containing Silymarin or a pharmaceutically acceptable salt thereof as an active ingredient. do.
  • the present invention provides a health food for the prevention and improvement of gastric damage, gastric ulcer or gastrointestinal diseases induced by alcohol containing silymarin or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention provides a method for the treatment of gastric injuries, gastric ulcers or the like, comprising administering an effective amount of silymarin or a pharmaceutically acceptable salt thereof to an individual suffering from alcohol-induced gastric injury, gastric ulcer or gastrointestinal disease. It provides a method of treating gastrointestinal diseases.
  • the present invention also provides a method for the prevention of gastric injury, gastric ulcer or gastrointestinal disease induced by alcohol, comprising administering to a subject an effective amount of silymarin or a pharmaceutically acceptable salt thereof.
  • the present invention also provides silymarin or a pharmaceutically acceptable salt thereof for use in a composition for the prevention, amelioration or treatment of alcohol-induced gastric injury, gastric ulcer or gastrointestinal disease.
  • the present invention also provides the use of an effective amount of silymarin or a pharmaceutically acceptable salt thereof for the preparation of a composition for the prevention, amelioration or treatment of gastric injury, gastric ulcer or gastrointestinal disease induced by alcohol.
  • the present invention relates to the treatment of silymarin or its pharmaceutically acceptable salts to reduce gastric damage induced by ethanol, to recover gastric mucus, to partially involve or restore the amount of silymarin and to inhibit the amount of gastric ulcers.
  • the composition comprising the silymarin or its pharmaceutically acceptable salt is excessive It may be useful for preventing or treating the stomach ulcer caused by drinking or the like for the pharmaceutical composition and health food.
  • Figure 1 is a gastric ulcer-induced model administered with ethane in the rat, after the pretreatment of silymarin and stilin, a positive control for each concentration, the area of gastric injuries is reduced as a result of confirming gastric area damage.
  • Figure 2 is a diagram showing that the amount of gastric mucus leans the result of measuring the amount of recovery of gastric mucus according to the pretreatment of silymarin by concentration in the ethanol-induced gastric ulcer model.
  • 3 is a diagram showing that the effect of inhibiting gastric ulceration by silymarin is reduced when pretreatment by concentration of NEM to determine the mechanism for the ethanol-induced gastric ulcer of silymarin.
  • Figure 4 shows that the ethanol-induced gastric mucosa model was significantly reduced as a result of the presence of gastric mucosa and the measure of damage to NP-SH, but the amount of NP-SH is recovered as a result of silymarin treatment.
  • FIG. 5 is a diagram showing that the effect of gastric ulceration by silymarin is reduced when L-NAME, an inhibitor of nitric oxide producing enzyme, is pretreated in ethanol-induced gastric ulcer.
  • the present invention provides a pharmaceutical composition for the prevention and treatment of gastric injury, gastric ulcer or gastrointestinal disease induced by alcohol containing Silymarin or a pharmaceutically acceptable salt thereof as an active ingredient.
  • silymarin is a compound represented by the following [Formula 1].
  • the chemical name is
  • the silymarin was determined by measuring the area of the gastric injury site after treating styrene according to the concentration of styrene used in the ethanol-induced gastric ulcer animal rat and styrene widely used as a therapeutic agent for gastric ulcer as a positive control. When pretreatment was performed, it was confirmed that the gastric damage area was reduced in a concentration-dependent manner (see FIG. 1).
  • NP-SH As a result of checking the effect of silymarin treatment on the NP-SH level, NP-SH was significantly reduced when ethane was administered to induce gastric injuries, but when silymarin was treated, the concentration of NP-SH was recovered ( See FIG. 4).
  • the effect of pretreatment of L-NG-nitroarginine methyl ester on the inhibition of silymarin on ethanol-induced gastric ulcer was confirmed that the pretreatment of LN ⁇ E decreased the effect of silymarin on gastric ulcer inhibition. It was confirmed that nitric oxide was partially involved in the gastric ulcer inhibitory effect (see FIG. 5). According to the above results it can be usefully used as a pharmaceutical composition for the prevention and suppression of gastric injury, gastric ulcer or gastrointestinal diseases induced by alcohol containing silymarin or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the silymarin compound according to the present invention may be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful.
  • Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid, aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and Obtained from non-toxic organic acids such as alkanedioates, aromatic acids, aliphatic and aromatic sulfonic acids.
  • These pharmaceutically toxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrile 0 phosphate, monohydrogen phosphate, dihydrogen phosphate 0 ⁇ metaphosphate, pyrophosphate chloride, bromide , Iodine o fluoride, acetate, propionate, decanoate, capryl o acrylate, formate, isobutyrate, caprate, heptano o o propirate, oxalate, malonate, succinate, subverate , Sebacque o fumarate, maleate ⁇ butine -1,4-dioate, nucleic acid -1,6-dioe o benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoe o hydroxybenzoate Oxybenzoate, phthalate, terephthale o benzenesulfonate, toluen
  • the acid addition salts according to the invention are prepared by conventional methods, for example, by dissolving the silymarin compound in an excess of an aqueous solution of an acid, using the salt with a miscible organic solvent such as methanol, ethane, acetone or acetonitrile. This mixture may be prepared by evaporation of a solvent or excess acid, followed by drying, or by precipitation filtration of the precipitated salt.
  • a miscible organic solvent such as methanol, ethane, acetone or acetonitrile.
  • Bases can also be used to make pharmaceutically acceptable metal salts.
  • Alkali metal or alkaline earth metal salts are obtained, for example, by dissolving the compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the compound salt at no cost, and evaporating and drying the filtrate.
  • the metal salt it is pharmaceutically suitable to prepare sodium, potassium, or chamomile salt.
  • Corresponding silver salts are also obtained by reacting an alkali or alkaline earth metal salt with a suitable silver salt (eg silver nitrate).
  • Silymarin compounds according to the invention include not only pharmaceutically acceptable salts thereof, but also isomers thereof or possible solvates or hydrates that may be prepared therefrom.
  • silymarin compound according to the present invention may be commercially available or synthesized using conventional synthetic methods known in the art of organic synthesis.
  • the silymarin compound or a pharmaceutically acceptable salt thereof according to the present invention reduces the gastric damage induced by ethanol, restores the amount of gastric mucus, partially participates in or restores the amount of silymarin and NP-SH which has an inhibitory effect on gastric ulcer. By confirming that nitric oxide is involved in gastric ulcer inhibitory effect, it can be usefully used for preventing or treating gastric ulcer.
  • the pharmaceutical composition containing the silymarin compound or a pharmaceutically acceptable salt thereof according to the present invention as an active ingredient may be formulated in various oral or parenteral dosage forms as follows, but is not limited thereto.
  • Formulations for oral administration include, for example, tablets, pills, hard / soft capsules, solutions, suspensions, emulsifiers, syrups, granules, elixirs, and the like.
  • One or more diluents or excipients such as layering agents, extenders, wetting agents, disintegrating agents, lubricants, binders, surfactants, and the like can be used.
  • Agar, starch, alginic acid or its sodium salt, calcium monohydrogen phosphate salt, etc. may be used as the boron , release agent, and silica, talc, stearic acid or its magnesium salt or calcium salt, polyethylene glycol, etc. may be used as a lubricant.
  • a binding agent is a magnesium aluminum silicate, starch paste, gelatin
  • Tra is such kanseu, methyl selreul as agarose, sodium carboxymethylcellulose selreul agarose, a polyvinylidene blood, low-substituted hydroxy propyl selreul agarose can be used, .
  • lactose, text, ossuose sucrose, manny, sorbide, cellulose, glycine and the like can be used as a diluent, and in some cases, commonly known boiling mixture absorbers, colorants, flavors, sweeteners, etc. Can be used together.
  • composition can be administered parenterally, parenteral administration is by the method of injecting subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection.
  • silymarin compound or a pharmaceutically acceptable salt thereof is mixed in water together with a stabilizer or a laxative to prepare a formulation for parenteral administration in water or as a solution or suspension, which is in unit dosage form of 3 ⁇ 4ple or vial. It can manufacture.
  • the pharmaceutical composition according to the present invention may be sterilized or contain preservatives, stabilizers, hydrating or emulsifiers, salts for controlling osmotic pressure, adjuvant such as buffers, and other therapeutically useful substances. It can be formulated according to the method of mixing, granulation or coating. If necessary, the additive composition according to the present invention may be combined with other drugs, for example, other therapeutic agents. It may also be administered.
  • composition according to the present invention may further include suitable carriers, excipients and diluents commonly used in the manufacture of a medicament.
  • composition according to the invention formulated into powders, granules, jeongge, capsules, suspensions, emulsions, syrups, oral dosage form for external application, in the form of a suppository, and sterile injection solution, such as an aerosol in a usual manner, respectively Can be used.
  • Carriers, excipients, and diluents that may be included in the compositions of the present invention include lactose, dextrose, sucrose, sorbbi, manny, xili, erythri, maltyl, starch, acacia rubber, alginate, gelatin, Calcium phosphate, calcium silicate, cellulose, methyl cellulose microcrystalline cellulose, polyvinyl pyridone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations include at least one excipient in the composition of the present invention, for example, calcium carbonate, sucrose ( sucrose) or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.
  • Liquid preparations for oral use include suspensions, solvents, emulsions, and syrups.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories.
  • non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate and the like can be used.
  • the active ingredient contains a silymarin compound or a pharmaceutically acceptable salt thereof in a unit dose of about 0.1 to 1,500 mg. Dosage depends on the doctor's prescription depending on factors such as the patient's weight, age and the specific nature and severity of the disease. However, the dosage required for adult treatment typically ranges from about 1 to 500 mg per day, depending on the frequency and intensity of administration. Intramuscular or intravenous administration to adults will be divided into single doses, usually at a total dosage of about 5 to 300 mg per day, but a higher daily dose may be desirable for some patients.
  • the preferred dosage of the pharmaceutical composition according to the present invention depends on the condition and the condition of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art.
  • the composition of the present invention is preferably administered at 0.00 to 0.03 g / kg, preferably 0.0 to 8 mg / kg per day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
  • the present invention provides a health food for the prevention and improvement of gastric damage, gastric ulcer or gastrointestinal diseases induced by alcohol containing silymarin or a pharmaceutically acceptable salt thereof as an active ingredient.
  • silymarin is a compound represented by the following [Formula 1].
  • the chemical name is
  • the silymarin compound or a pharmaceutically acceptable salt thereof according to the present invention enjoys gastric damage induced by ethanol, restores gastric mucus volume, partially participates in or restores the amount of NP—SH having an inhibitory effect of gastric ulcer, and By confirming that nitric oxide is involved in the gastric ulcer inhibitory effect of silymarin, alcoholic gastric ulcer prevention and improvement health foods can be usefully used in the composition.
  • alcoholic gastric ulcer prevention and improvement health foods can be usefully used in the composition.
  • Silymarin or a pharmaceutically acceptable salt thereof of the present invention may be added to a food as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method.
  • the mixed amount of the active ingredient can be suitably determined according to the purpose of use (prevention or improvement).
  • the amount of the extract in the health food can be added to 0.1 to 90 parts by weight of the total food weight.
  • the amount may be below the above range.
  • the active ingredient since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
  • the functional beverage composition of the present invention contains the extract as an essential ingredient in the indicated ratio.
  • the other ingredients may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
  • natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like, and xylyl, sorbitol, erythritol and the like.
  • natural flavoring agents tautin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavorings (saccharin, aspartame, etc.) can be advantageously used.
  • the proportion of natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 compositions of the present invention.
  • the silymarin or a pharmaceutically acceptable salt thereof of the present invention may contain various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, and flavors, colorants and neutralizers (such as cheese and chocolate). And salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like.
  • the extract of the present invention may contain a fruit flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components can be used independently or in combination.
  • the present invention provides a method for the treatment of gastric injuries, gastric ulcers or It provides a method of treating gastrointestinal diseases.
  • the present invention also provides a method for the prevention of gastric injury, gastric ulcer or gastrointestinal disease induced by alcohol, comprising administering to a subject an effective amount of silymarin or a pharmaceutically acceptable salt thereof.
  • the present invention also provides silymarin or a pharmaceutically acceptable salt thereof for use in a composition for the prevention, amelioration or treatment of alcohol-induced gastric injury, gastric ulcer or gastrointestinal disease.
  • the present invention also provides the use of an effective amount of silymarin or a pharmaceutically acceptable salt thereof for the preparation of a composition for the prevention, amelioration or treatment of gastric injury, gastric ulcer or gastrointestinal disease induced by alcohol.
  • an effective amount of silymarin or a pharmaceutically acceptable salt thereof for the preparation of a composition for the prevention, amelioration or treatment of gastric injury, gastric ulcer or gastrointestinal disease induced by alcohol.
  • the following Examples, Experimental Examples and Preparation Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Examples, Experimental Examples, and Preparation Examples.
  • the following Examples, Experimental Examples and Preparation Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Examples, Experimental Examples, and Preparation Examples.
  • Example 1 Isolation and Identification of Silymarin
  • Example 1 Five male SD (Spr ague-Daw ley) rats (Cortech, Korea) at 7 weeks of age were fasted for 36 hours with 1 group, and then the silymarin prepared in Example 1 was 25 , 50, 100, 200 mg / kg orally and 30 minutes later, 1 ml of 100% ethanol (ethanol) and fasted water saving for 1 hour After letting it die for co 2 .
  • ligation of the pylorus and esophagus put 10 ml of 2% formalin solution in the stomach, fix it for 10 minutes, and incision of the Taiwanese section, photographing the damaged area with a digital camera. The total was taken as the damage index as measured in (Image-Pro Plus 4.5.1). Damage area is expressed as 3 ⁇ 4> of the total distal area. Stillene was used as a control drug.
  • the gastric ulceration mechanism by ethanol promotes gastric mucosal permeability and inhibits active transport, causing gastric injury.
  • the stomach secretes a protective fluid to protect the mucosal layer.
  • the normal control group had a 235,000 mg / g tissue of Alcian blue, while the solvent control group had a mucus reduction of 161.3 mg / g tissue.
  • silymarin was treated at concentrations of 100 mg / kg and 200 mg / kg, mucus recovered to 200.7 mg / g tissue and 227.9 mg / g tissue, respectively.
  • gastric mucus recovers in a concentration-dependent manner when treated with silymarin (FIG. 2).
  • NP-SH including glutathione
  • glutathione is abundant in the gastrointestinal mucosa and is known as a measure of the presence and extent of gastric mucosal damage. Thus, the effect of silymarin treatment on the amount of NP-SH was confirmed.
  • the amount of NP-SH was reduced to 252.2 mg / g tissue in the normal group, while the amount of NP-SH was reduced to 60.6 mg / g in the solvent control group.
  • silymarin was treated at 100 mg / kg and 200 mg / kg concentrations, the mucus recovered to 113.4 mg / g tissue and 160.6 mg / g tissue, respectively. Although significantly reduced, it was confirmed that the amount of NP-SH was recovered when the silymarin was treated (concentration 4).
  • Nitric oxide is known to have a function of protecting gastric damage by participating in blood flow and vasodilation of the gastrointestinal tract.
  • L-NG-nitroarginine methyl The effect of ester pretreatment on the inhibition of silymarin on ethanol induced gastric ulcer was confirmed.
  • the capsule was prepared by filling in gelatin capsule according to a conventional method for preparing capsules.
  • Silymarin was added to 0.5-5.0 parts by weight of wheat flour, and the mixture was used to prepare bread, cakes, cookies, crackers and noodles to prepare health promoting foods.
  • Silymarin was added to 5 to 10 parts by weight of milk, using the milk to prepare a variety of dairy products such as butter and ice cream.
  • Brown rice, barley, sesame rice, and yulmu were alphad by a known method, and then dried and roasted to prepare a powder having a particle size of 60 mesh.
  • Black beans, black sesame seeds, and sesame seeds were also steamed and dried by a known method, and then ground to a powder having a particle size of 60 mesh.
  • Silymarin was concentrated under reduced pressure in a vacuum concentrator; the dried product obtained by spraying and drying with a hot air dryer was pulverized with a particle size of 60 mesh using a grinder to obtain a dry powder.
  • Cereals (30 parts by weight brown rice, 15 parts by weight brittle, 20 parts by weight of barley) ,
  • Seeds (7 parts by weight perilla, 8 parts by weight black beans, 7 parts by weight black sesame seeds),
  • Vitamin B6 0.5 nig
  • Vitamin B12 0.2 / g
  • composition ratio of the above vitamin and mineral mixture is relatively
  • the ingredients are mixed in a preferred embodiment, the blending ratio may be arbitrarily modified.
  • the above ingredients are mixed according to a conventional health food manufacturing method, then granules are prepared and a health food composition is prepared according to a conventional method. Can be used for
  • the above ingredients were mixed according to the method of preparing 500 general health drinks, and then stirred and heated at 85 ° C. for about 1 hour, and then the resulting solution was filtered and obtained in a sterilized 1 f container and sealed and sterilized. It is then used to prepare the health beverage composition of the present invention.
  • composition ratio is a combination of relatively suitable components for a preferred beverage in a preferred embodiment
  • the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as the demand hierarchy, the country of use, the intended use.
  • the present invention is not limited to the embodiments, experimental examples, and preparation examples described above, and various modifications and changes may be brought by those skilled in the art, and the present invention is defined in the spirit and scope of the present invention as defined in the appended claims. Included. Industrial Applicability
  • the present invention is a composition containing silymarin or a pharmaceutically acceptable salt thereof may be useful for the development of pharmaceutical compositions and health foods for preventing or treating gastric ulcers or gastrointestinal diseases caused by excessive drinking. Can be.

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Abstract

La présente invention concerne une composition contenant de la silymarine ou son sel pharmaceutiquement acceptable en tant que principe actif pour l'inhibition d'ulcères peptiques provoqués par la consommation d'alcool. Plus particulièrement, il a été déterminé que la silymarine réduit les lésions gastriques provoquées par l'éthanol, récupère une quantité de mucus gastrique, et est en partie impliquée dans la récupération d'une quantité de NP-SH qui a pour effet d'inhiber les ulcères peptiques, et que l'oxyde nitrique est associé aux effets inhibiteurs de l'ulcère peptique de la silymarine ; aussi, la silymarine et son sel pharmaceutiquement acceptable peuvent être utilisés efficacement pour une composition pharmaceutique ou un aliment naturel pour la prévention, le soulagement ou le traitement d'ulcères peptiques provoqués par une consommation excessive d'alcool.
PCT/KR2013/001377 2012-06-11 2013-02-21 Composition comprenant de la silymarine en tant que principe actif pour la prévention et le traitement d'ulcères peptiques provoqués par la consommation d'alcool WO2013187576A1 (fr)

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KR1020120062230A KR101446743B1 (ko) 2012-06-11 2012-06-11 실리마린을 유효성분으로 포함하는 알콜성 위궤양 예방 및 치료용 조성물
KR10-2012-0062230 2012-06-11

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