[go: up one dir, main page]

WO2010117194A2 - Composition pour prévenir ou traiter des troubles gastriques contenant un composant actif comprenant un composé de la série des acides gras - Google Patents

Composition pour prévenir ou traiter des troubles gastriques contenant un composant actif comprenant un composé de la série des acides gras Download PDF

Info

Publication number
WO2010117194A2
WO2010117194A2 PCT/KR2010/002105 KR2010002105W WO2010117194A2 WO 2010117194 A2 WO2010117194 A2 WO 2010117194A2 KR 2010002105 W KR2010002105 W KR 2010002105W WO 2010117194 A2 WO2010117194 A2 WO 2010117194A2
Authority
WO
WIPO (PCT)
Prior art keywords
acid
ethyl ester
acid ethyl
ester
group
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2010/002105
Other languages
English (en)
Korean (ko)
Other versions
WO2010117194A3 (fr
Inventor
최원식
장도연
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Daewon Pharm Co Ltd
Original Assignee
Daewon Pharm Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Daewon Pharm Co Ltd filed Critical Daewon Pharm Co Ltd
Publication of WO2010117194A2 publication Critical patent/WO2010117194A2/fr
Publication of WO2010117194A3 publication Critical patent/WO2010117194A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • 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

  • the present invention relates to a composition for preventing and / or treating gastrointestinal diseases, which contains a fatty acid-based compound having a gastrointestinal disease therapeutic effect as an active ingredient.
  • the present invention contains fatty acid-based compounds having a gastrointestinal disease treatment effect as an active ingredient, and the foods stored through the esophagus are easily broken down and easily digested, and the foods are sent to the duodenum to regulate the secretion of pancreatic enzymes. It is an organ that allows digestion and absorption.
  • the stomach secretes gastric acid, a strong acid, to digest food when it comes in.
  • the mucosal protective layer acts to prevent the gastric mucosa from being damaged by gastric acid.
  • Factors that adversely affect the functioning of the gastrointestinal system of humans are extremely diverse. Such disorders can occur in the upper gastrointestinal tract, lower gastrointestinal tract, or both, and there are a wide range of gastrointestinal disorders, including genetic, physiological, environmental, and mental factors.
  • Chronic diseases of the upper gastrointestinal tract include gastritis and gastric ulcers, and inflammation occurs when gastric acid secretion is increased or gastric mucosal protective layers are damaged by various causes.
  • gastric ulcers When the inflammatory lesions are limited to the gastric mucosa, gastritis, or gastric ulcers that form through the gastric mucosa and submucosal tissues and muscle layers are called gastric ulcers. Ulcers in the duodenum are also called duodenal ulcers, and stomach and duodenal ulcers are collectively called peptic ulcers.
  • Drugs used to treat gastrointestinal diseases such as gastritis and peptic ulcers are mainly used to reduce gastric acid, pepsin, and stress, which are factors that promote and recur ulcers. Drugs are the most used.
  • Conventional treatments for gastritis and peptic ulcers include antacids that neutralize excessive gastric secretions, histamine H 2 receptor antagonists and proton pump inhibitors that inhibit gastric acid secretion, and increased gastrointestinal resistance to digestive fluids.
  • Antacids in the drug are intended for temporary fastening, not for fundamental treatment, and show efficacy by increasing pH in the stomach to lower the activity of pepsin.
  • side effects such as constipation, diarrhea, metabolic alkalosis, urolithiasis, etc. have been reported by the administration of an inorganic substance, and in recent years, acid rebound due to antacids has been a problem.
  • Cimetidine the most widely used H 2 receptor antagonist, blocks histamine receptors in the gastric mucosa and blocks histamine molecules so that the histamine molecules do not signal acid secretion.
  • Full-scale treatment of peptic ulcer began with the release of cimetidine in 1977, and several derivatives have been developed. Among them, ranitidine, famotidine, roxatidine, and nizatidine have excellent anti-ulcer effects in clinical practice due to the shortening of the treatment period. The disadvantage is the high recurrence rate.
  • cimetidine has side effects such as neutropenia and drug interactions, and thus avoids its use, and the most recent drugs, such as ranitidine and pamotidine, are greatly reduced in long-term use.
  • proton pump inhibitors include omeprazole, omeprazole, lansoprazol, and pantoprazole, which are known to exhibit potent acid secretion effects by inhibiting acid secretion in gastric wall cells in the final stage.
  • prostaglandin biosynthesis-promoting gastric mucosal diseases such as misoprostol, artemisiae argyi Folium extract, teprenone, and the like, and there is rebamipide, a gastrin receptor inhibitor.
  • the relapse rate has not been reduced even in ulcer healing patients with these drugs, and side effects such as stool, diarrhea, fever, headache and fatigue have been reported.
  • Another object of the present invention is a fatty acid and fatty acid ester, or a pharmaceutically acceptable salt thereof (first component), an H 2 receptor antagonist, a proton pump inhibitor, a gastrin receptor inhibitor, and a gastric mucosa protective agent (treatment for gastric mucosal disease) It is to provide a composite formulation composition for the prevention and / or treatment of gastrointestinal diseases comprising at least one (second component) selected from the group consisting of.
  • the present invention provides a composition for preventing and / or treating gastrointestinal diseases, which contains a fatty acid and fatty acid ester, or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention also relates to fatty acids and fatty acid esters, or pharmaceutically acceptable salts thereof (first component), H 2 receptor antagonists, proton pump inhibitors, gastrin receptor inhibitors, gastric mucosa protective agents (gastric mucosal disease agents), and the like. It provides a composite formulation composition for the prevention and / or treatment of gastrointestinal diseases comprising at least one (second component) selected from the group consisting of.
  • the present invention provides a composition for protecting the stomach wall, which contains a fatty acid and fatty acid ester, or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention also relates to fatty acids and fatty acid esters, or pharmaceutically acceptable salts thereof (first component), H 2 receptor antagonists, proton pump inhibitors, gastrin receptor inhibitors, gastric mucosa protective agents (gastric mucosal disease agents), and the like. It provides a composition for protecting the stomach wall comprising at least one (second component) selected from the group consisting of.
  • the fatty acid or ester compound thereof according to the present invention is expected to be useful in the treatment of gastrointestinal diseases because of its excellent protective and / or therapeutic effect on the gastric wall, especially when used in combination with other active ingredients with gastric acid removal effect. It is expected to be.
  • Figure 1 shows the gas chromatographic results of the methylene chloride extract of the worm mushroom mycelium culture (HEAC) cultured in the ginko mugwort medium.
  • Figure 2 is a graph showing the gastric lesion rate with time after administration of the fatty acid-based compound according to the present invention.
  • Figure 3 is a graph showing the treatment rate of gastric lesions with time after administration of a fatty acid-based compound according to the present invention.
  • the present invention is a gastric wall containing at least one compound selected from the group consisting of saturated fatty acids, alkyl ester compounds of the saturated fatty acids, unsaturated fatty acids and alkyl ester compounds of the unsaturated fatty acids, or pharmaceutically acceptable salts thereof.
  • compositions for protection, prevention or treatment of gastrointestinal diseases are provided.
  • the present invention comprises at least one compound (first component) selected from the group consisting of saturated fatty acids, alkyl ester compounds of the saturated fatty acids, unsaturated fatty acids and alkyl ester compounds of the unsaturated fatty acids; At least one selected from the group consisting of H 2 receptor antagonists, proton pump inhibitors, gastrin receptor inhibitors, gastric mucosa protectors and extracts of Hericium erinaceum Hypha Cultivated with Artemisia capillaries (HEAC) It provides a composition for protecting the stomach wall, preventing or treating gastrointestinal diseases, including.
  • first component selected from the group consisting of saturated fatty acids, alkyl ester compounds of the saturated fatty acids, unsaturated fatty acids and alkyl ester compounds of the unsaturated fatty acids
  • the saturated fatty acid may use 4 to 40 carbon atoms, preferably 4 to 14 or 20 to 40 saturated fatty acids, for example, butyric acid and caproic acid.
  • the unsaturated fatty acid may use 8 to 30 carbon atoms, preferably 8 to 16 or 20 to 30 unsaturated fatty acids, for example, dehydromatricaria acid, Unde Undecenoic acid, Hydnocarpic acid, Palmitoleic acid, Chaulmoogric acid, Malvallic acid, Oleic acid, Ricinoleic acid ( Ricinoleic acid, Vaccenic acid, Linoleic acid, Crepenynic acid, Dehydrocrepenynic acid, Linolenic acid, Stearidonic acid, Stekuldonic Sterculic acid, Gadoleic acid, Dihomo- ⁇ -Linolenic acid (DHLA), Eicosatetraenoic acid, Arachidonic acid, Eicosapentaenoic acid, EPA ), Erucic acid, Chi Acid (Cichoric acid), may be at least one member selected from Toko Inc.
  • dehydromatricaria acid Unde Undecenoic acid, Hydnocarpic acid, Palmito
  • pentamethyl the group consisting of acid (Docosapentaenoic acid, DPA), acid to docosahexaenoic (Docosahexaenoic acid, DHA), and a tunnel acid (Nervonic acid) to.
  • DPA Docosapentaenoic acid
  • DHA Docosahexaenoic acid
  • Nevonic acid a tunnel acid
  • one or more selected from the group consisting of oleic acid, linoleic acid, dihydrocrefenic acid, docosahexaenoic acid, and arachidonic acid may be used as the fatty acid, and most preferably linoleic acid may be used.
  • the alkyl ester compound may be an ester compound of a fatty acid having an alkyl group having 1 to 4 carbon atoms, preferably a methyl group or an ethyl group, and more preferably an ethyl group.
  • the alkyl ester compound of saturated fatty acid may be at least one compound selected from the group consisting of methyl or ethyl ester compounds of 4 to 40 carbon atoms, preferably 4 to 14 or 20 to 40 saturated fatty acids.
  • the alkyl ester compound of the unsaturated fatty acid may be at least one compound selected from the group consisting of methyl or ethyl ester compounds of 8 to 30 carbon atoms, preferably 8 to 16 or 20 to 30 unsaturated fatty acids.
  • ester compounds of saturated fatty acids include butyric acid ethyl ester, caproic acid ethyl ester, caprylic acid ethyl ester, and capric acid ethyl ester.
  • esters lauric acid ethyl esters, myristic acid ethyl esters, tetramethyl decanoic acid ethyl esters, and palmitic acid ethyl esters esters, stearic acid ethyl esters, dihydrosterculic acid ethyl esters, tuberculostearic acid ethyl esters, arachidic acid esters acid ethyl ester, Behenic acid ethyl ester, Lignoceric acid ethyl ester, Selected from the group consisting of cerotic acid ethyl ester, montanic acid ethyl ester, melissic acid ethyl ester, and corynomy
  • At least one selected from the group consisting of oleic acid ethyl ester, linoleic acid ethyl ester, dihydrocrephenic acid ethyl ester, docosahexaenoic acid ethyl ester, and arachidonic acid ethyl ester may be used as the ester compound of the fatty acid, Most preferably linoleic acid ethyl ester can be used.
  • the fatty acid or ester compound thereof according to the present invention has an excellent effect of protecting the gastric wall and suppressing gastritis-gastric ulcer lesions (see Tables 2 and 3), and also has a therapeutic effect in the occurrence of gastritis-gastric ulcers over the effects of conventional gastrointestinal disease treatments. (See Table 17).
  • the fatty acids and / or ester compounds thereof may also be treated with conventional gastrointestinal disorders such as H 2 receptor antagonists and / or proton pump inhibitors and / or gastrin receptor inhibitors and / or gastric mucosal diseases with gastric acid regulating effects (gastric mucosal disease When used in combination with a therapeutic agent) and the like, since gastric acid regulation effect and gastric wall protective effect can be obtained at the same time, more excellent gastrointestinal disease prevention and / or therapeutic effect can be exhibited.
  • conventional gastrointestinal disorders such as H 2 receptor antagonists and / or proton pump inhibitors and / or gastrin receptor inhibitors and / or gastric mucosal diseases with gastric acid regulating effects (gastric mucosal disease When used in combination with a therapeutic agent) and the like, since gastric acid regulation effect and gastric wall protective effect can be obtained at the same time, more excellent gastrointestinal disease prevention and / or therapeutic effect can be exhibited.
  • H 2 receptor antagonists such as ranitidine, cimetidine, pamotidine, roxatidine, nizatidine or omeprazole, eomeprazole, lansoprazole, pantoprazole, labeprazole, revaprazan ,
  • Proton pump inhibitors such as ilaprazole, gastrin receptor inhibitors such as levamipid, or gastric mucosa protective agents such as misoprostol and larvae extract, gastrointestinal mucosa disease agents, and H. pylori cultured in H.
  • aeruginosa medium Hericium erinaceum Hypha
  • HEAC Artemisia capillaries
  • the fatty acid or ester compound thereof according to the present invention protects the gastric wall and has an excellent effect of inhibiting gastritis-gastric ulcer lesions, and also has a therapeutic effect when gastritis-gastric ulcers occur, and when used with conventional therapeutic ingredients, gastric-gastric ulcer lesions Significantly increase the inhibitory effect can be useful as a gastric wall protection and gastrointestinal disease treatment.
  • Gastrointestinal diseases in which the compositions of the present invention have a prophylactic and / or therapeutic effect include reflux esophagitis, gastritis, duodenitis, gastric ulcer, duodenal ulcer, digestive disorders associated with nonsteroidal anti-inflammatory drugs (NSAIDs), non-ulcer dyspepsia, gastritis Reflux disease, gastrinoma, acute upper gastrointestinal bleeding, stress ulceration, Helicobacter pylori infection, Zollinger-Ellison syndrome (ZES), Werner's syndrome, and systemic mastocytosis, but are not limited thereto.
  • NSAIDs nonsteroidal anti-inflammatory drugs
  • ZAS Zollinger-Ellison syndrome
  • ZES Werner's syndrome
  • systemic mastocytosis but are not limited thereto.
  • the H 2 receptor antagonist usable as the second component is cimetidine, ranitidine, pamotidine, loxatidine, nizatidine, and pharmaceutically acceptable salts, isomers and isomers thereof. It may be one or more selected from the group consisting of.
  • the proton pump inhibitor usable as the second component is omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole, revaprazan, ilaprazole, paraprazole, reminoprazole, and these It may be one or more selected from the group consisting of pharmaceutically acceptable salts thereof, enantiomers thereof and pharmaceutically acceptable salts of enantiomers.
  • the gastrin receptor inhibitor usable as the second component may be one or more selected from the group consisting of levamifeed and its pharmaceutically acceptable salts.
  • the gastric mucosa protective agent (the gastric mucosal disease agent) which can be used as the second component is misoprostol, a pharmaceutically acceptable salt thereof, and an extract of Artemisiae Argyi Folium (for example, 80 to 100).
  • v / v% ethanol extract may be one or more selected from the group consisting of, but is not limited thereto.
  • Helicium erinaceum Hypha Cultivated with Artemisia capillaries (HEAC) extracts cultured in the ginseng wormwood medium usable as the second ingredient are water, alcohols having 1 to 5 carbon atoms (e.g., 25 to 100 v / v%), hexane, chloroform, methylene chloride, acetonitrile, acetone, and ethyl acetate obtained by extraction with one or more solvents selected from the group consisting of; For example, 25 to 100 v / v%), hexane, methylene chloride, and ethyl acetate may be a fraction obtained by further adding one or more selected from the group consisting of.
  • the extraction method may be by any method commonly used in the preparation of plant extracts, for example, by stirring extraction, hot water extraction, etc., may be filtered and / or concentrated in a conventional manner after extraction.
  • the contents related to the extract of Roe deer fungus mycelium cultured in other Injin mugwort medium is as described in Korean Patent Application No. 10-2007-0108131.
  • the composition according to the present invention is a composite formulation composition
  • the composition is in a form in which the first component and the second component are formulated into one dosage form and are administered at one time, or the first component and the second component are formulated respectively or simultaneously or at a time interval. It includes all the forms to be administered.
  • the use ratio of the first component and the second component is 1: 0.1 to 5, preferably 1: 0.5 to 2 based on the weight ratio.
  • the dosage of the composition according to the present invention can be appropriately adjusted according to the condition, age, weight, degree of disease, route of administration, etc. of the patient, and once per day at regular time intervals or at regular time intervals according to the judgment of a doctor or pharmacist. It may be administered in divided doses over several days.
  • the dosage is based on the active ingredient content, 0.0001 mg / kg / day to 1000 mg / kg / day, preferably 0.01 mg / kg to 500 mg / kg, more preferably 0.01 mg / kg to 100 mg / kg may be, but is not limited thereto.
  • the above dosages are illustrative of the average case and may be high or low depending on individual differences.
  • the daily dose of the composition of the present invention is less than the dose, a significant effect may not be obtained, and if it exceeds the above, it may be uneconomical and out of the range of normal dose, which may cause undesirable side effects. It is good to set it as the said range.
  • composition according to the invention can be administered to a mammal, including humans, by various routes.
  • the mode of administration can be any of the routinely used forms and can be administered, for example, by oral, rectal or intravenous, intramuscular, or subcutaneous injection.
  • the compositions of the present invention may be formulated in oral dosage forms, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, or parenteral formulations in the form of transdermal, suppository, and sterile injectable solutions according to conventional methods. Can be used.
  • composition of the present invention may further contain an adjuvant such as a pharmaceutically suitable and physiologically acceptable carrier, excipient and diluent in addition to the active ingredient.
  • Carriers, excipients and diluents that may be included in the compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants can be used.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. ) Or lactose, gelatin and the like can be mixed.
  • lubricants such as magnesium styrate talc are also used.
  • Oral liquid preparations include suspending agents, liquid solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, transdermal agents and the like.
  • the non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.
  • As the base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • the composition of the present invention may be administered alone, but is generally mixed with a pharmaceutical carrier selected in consideration of the mode of administration and standard phamaceutical practice. May be administered.
  • a pharmaceutical carrier selected in consideration of the mode of administration and standard phamaceutical practice. May be administered.
  • the compositions of the present invention may be in the form of tablets containing starch or lactose, in the form of capsules alone or in the form of excipients, or in the form of elixirs or suspending agents containing chemicals to flavor or color. It can be administered orally, orally or sublingually.
  • Such liquid preparations may be suspending agents (e.g., semisynthetic glycerides such as methylcellulose, witepsol or mixtures of apricot kernel oil and PEG-6 esters or PEG-8 and caprylic / capric Pharmaceutically acceptable additives such as glyceride mixtures such as mixtures of glycerides).
  • suspending agents e.g., semisynthetic glycerides such as methylcellulose, witepsol or mixtures of apricot kernel oil and PEG-6 esters or PEG-8 and caprylic / capric
  • Pharmaceutically acceptable additives such as glyceride mixtures such as mixtures of glycerides).
  • Example 1 Preparation of mushroom mycelium extract cultured in Injin mugwort medium and identification of active ingredient
  • YMPG yeast extract malt extract-peptone-glucose
  • the solid medium in which the rotiferous mycelium mycelium was formed before the fruiting body formation obtained by the culture was dried to obtain a medicinal mycelium mycelium culture (Hericium erinaceum Hypha cultivated with Artemisia capillaries, hereinafter HEAC).
  • HEAC Hericium erinaceum Hypha cultivated with Artemisia capillaries
  • the GC analysis conditions are as follows:
  • Carrier gas helium
  • MS (mass spectrometery) spectrum was analyzed for each of the peaks of FIG. MS analysis conditions are as follows:
  • Carrier gas helium
  • each peak component was found as follows.
  • HEAC contained fatty acid-based compounds such as palmitic acid ethyl ester, oleic acid ethyl ester, stearic acid ethyl ester, linoleic acid ethyl ester and linolenic acid ethyl ester.
  • Example 1 In order to determine the gastric protective effect of the main components analyzed in Example 1, the following test was performed.
  • Example 1 Eight 7-week-old male (Sprague-Dawley) males (210 ⁇ 10 g) were grouped and fasted for 24 hours, and then the fatty acid-based compounds isolated in Example 1 were suspended in 5 mL of distilled water and a dose of 40 mg / kg. It was administered orally.
  • styrene tablets Long-A Pharm. Co., Ltd.
  • Selbex capsules which are conventionally used for treating gastritis-gastric ulcer, were used.
  • 1.5 mL of 150 mM HCl-EtOH (60%) solution was orally administered as a gastric lesion development reagent.
  • Gastric lesion inhibition rate was calculated by Equation 1 generally adopted in this field, and the significance test with the control group was Student's t-test, One-way Analysis of Variance (ANOVA) and Dunnett 'test.
  • the gastritis-gastric ulcer inhibitory effect of the HEAC main components obtained is shown in Table 1 (number of subjects: 8 for each sample).
  • the fatty acid ester compound contained in the HEAC exhibited gastritis-gastric ulcer inhibition rate of 47.3-78.5%, compared to the gastritis-gastric ulcer treatment rate (53.2 ⁇ 54.2%). It can be seen that it exhibits a gastric ulcer inhibitory effect. In particular, in the case of linoleic acid ethyl ester it was confirmed that the gastritis-gastric ulcer suppression effect is excellent by showing a 78.5% inhibition of gastritis-gastric ulcer even when used alone.
  • the fatty acid ester compound according to the present invention can be usefully used as a protective agent for gastric wall protection and gastrointestinal diseases because it has an excellent effect of protecting the gastric wall and inhibiting gastritis-gastric ulcer lesions.
  • stearic acid As shown in Table 2 and Table 3, stearic acid, arachidic acid, behenic acid, lignoceric acid, serotic acid, montanic acid, melisic acid, palmitoleic acid, oleic acid, ricinoleic acid, linoleic acid, crephenic acid, di Fatty acid compounds such as hydrocrefenic acid, linolenic acid, stearic acid, DHLA, eicosatetraenoic acid, arachidonic acid, eicosapentaenoic acid, chicoric acid, docosapentaenoic acid, docosahexaenoic acid, or ethyl ester compounds thereof Showed more than 50% gastritis-gastric ulcer inhibition rate.
  • linoleic acid showed a gastritis-gastric ulcer inhibition rate of 71.3% for fatty acids and 78.5% for ester compounds.
  • the fatty acid or ester compound thereof according to the present invention can be usefully used as a protective agent for gastric wall protection and gastrointestinal diseases because it has an excellent effect of protecting the gastric wall and inhibiting gastritis-gastric ulcer lesions.
  • ranitidine alarm drug
  • cimetidine light drug
  • pamotidine Hami drug
  • loxatidine Lotte drug
  • nizatidine Korea Nelson
  • the effect of inhibiting gastric lesions was measured in the same manner as in Example 2 except that the pharmaceutical was administered in a 1: 1 combination by weight.
  • ester compounds of fatty acids and H 2 such as oleic acid ethyl ester, linoleic acid ethyl ester, dihydrocrefeninic acid ethyl ester, docosahexaenoic acid ethyl ester, arachidonic acid ethyl ester, etc. when administered in combination receptor antagonists, H 2 receptor antagonist administered alone when more gastritis - was found to be a gastric ulcer inhibition rate is significantly raised, in particular the case of using linoleic acid ethyl ester is gastritis than in the H 2 receptor antagonist administration alone-ulcer Inhibition rate increased by more than 20%.
  • the fatty acid or ester compound thereof according to the present invention can be usefully used as a protective agent for gastric wall protection and gastrointestinal diseases because it has an excellent effect of protecting the gastric wall and inhibiting gastritis-gastric ulcer lesions.
  • omeprazole (Ceun Kun Dang), lansoprazole (Ankuk Pharmaceutical), pantoprazole (Hanbul Pharmaceuticals), labeprazole (Binex), revaprazan (Yuhan Corporation), ilaprazole (Ilyang Pharm.) And E. methprazole (Hanmi Pharm) was measured in the same manner as in Example 2 except for the combined administration of the weight ratio of gastric lesions was measured.
  • ester compounds and proton pumps of fatty acids according to the invention such as oleic acid ethyl ester, linoleic acid ethyl ester, dihydrocrefeninic acid ethyl ester, docosahexaenoic acid ethyl ester, arachidonic acid ethyl ester Concomitant inhibitors showed significantly higher gastritis-gastric ulcer inhibition rates than proton pump inhibitors alone, especially when linoleic acid ethyl ester was used. Rising over%.
  • the fatty acid or ester compound thereof according to the present invention can be usefully used as a protective agent for gastric wall protection and gastrointestinal diseases because it has an excellent effect of protecting the gastric wall and inhibiting gastritis-gastric ulcer lesions.
  • Example 2 The same method as in Example 2, except that the fatty acid-based compound tested in Example 3 and styrene (Dong-A Pharmaceutical), Misoprostole (LS drug) 1: 1 in combination by weight as a gastric mucosa protective agent Gastric lesion inhibition effect was measured by.
  • LS drug Misoprostole
  • ester compounds and gastric mucosa of fatty acids according to the present invention such as oleic acid ethyl ester, linoleic acid ethyl ester, dihydrocrefeninic acid ethyl ester, docosahexaenoic acid ethyl ester, arachidonic acid ethyl ester, etc.
  • the gastritis-gastric ulcer inhibition rate was significantly higher than that of the gastric mucosal protective agent alone.
  • the gastritis-gastric ulcer inhibition rate was 20 higher than that of the gastric mucosal protective agent alone. Rising over%.
  • the fatty acid or ester compound thereof according to the present invention can be usefully used as a protective agent for gastric wall protection and gastrointestinal diseases because it has an excellent effect of protecting the gastric wall and inhibiting gastritis-gastric ulcer lesions.
  • Example 3 The effect of inhibiting gastric lesions was measured in the same manner as in Example 2, except that 1: 1 combination of levamifeed (Yangyang Pharm.) As a fatty acid-based compound and gastrin receptor inhibitor tested in Example 3 was used. It was.
  • a combination of an ester compound of a fatty acid according to the present invention and a gastrin receptor inhibitor such as oleic acid ethyl ester, linoleic acid ethyl ester, dihydrocrephenic acid ethyl ester, docosahexaenoic acid ethyl ester, arachidonic acid ethyl ester, etc.
  • the gastritis-gastric ulcer inhibition rate was significantly higher than that of the gastrin receptor inhibitor alone.
  • the gastritis-gastric ulcer inhibition rate was increased by 20% or more. Appeared to be.
  • the fatty acid or ester compound thereof according to the present invention can be usefully used as a protective agent for gastric wall protection and gastrointestinal diseases because it has an excellent effect of protecting the gastric wall and inhibiting gastritis-gastric ulcer lesions.
  • Example 2 The effect of inhibiting gastric lesions was measured in the same manner as in Example 2, except that the fatty acid-based compound tested in Example 3 and the HEAC extract were administered in a 1: 1 combination.
  • the HEAC extract was prepared as follows as an ethanol extract of the worm mushroom mycelium cultured in jinjin wormwood. 400.0 mL of 80% ethanol was added to 40.0 g of the dried mycelium of the Roe mite mushroom cultured in the Injingumi medium described in Example 1, stirred and extracted at about 40 ° C. for 24 hours, and filtered at about 40 ° C. to obtain the primary extract. Got it. The obtained primary extract was refrigerated. Then, 400.0 mL of 80% ethanol was added to the residue of the first extract, followed by stirring extraction at about 40 ° C. for 8 hours, and filtered at about 40 ° C. to obtain a second extract. Finally, after mixing the first and second extract prepared by the above-described manufacturing process, concentrated to obtain 4.4 g (yield 11.0%) was used as the HEAC extract of this embodiment.
  • a fatty acid ester compound and HEAC extract according to the present invention such as oleic acid ethyl ester, linoleic acid ethyl ester, dihydrocrephenic acid ethyl ester, docosahexaenoic acid ethyl ester, arachidonic acid ethyl ester, etc.
  • gastric inflammation-gastric ulcer inhibition rate was significantly higher than HEAC extract alone administration, and especially linoleic acid ethyl ester increased gastritis-gastric ulcer inhibition rate more than 25% than HEAC extract alone administration.
  • the fatty acid or ester compound thereof according to the present invention can be usefully used as a protective agent for gastric wall protection and gastrointestinal diseases because it has an excellent effect of protecting the gastric wall and inhibiting gastritis-gastric ulcer lesions.
  • Example 2 and the above except that the fatty acid-based compound tested in Example 3 to prepare a combination formulation by adding a ranitidine, omeprazole, styrene or HEAC extract 1: 1 by weight based on the dosage and administering the combination formulation by dose In the same way, the effect of inhibiting gastric lesions was measured.
  • ester compounds of fatty acids according to the present invention such as oleic acid ethyl ester, linoleic acid ethyl ester, dihydrocrefeninic acid ethyl ester, docosahexaenoic acid ethyl ester, and conventional gastritis-gastric ulcer therapeutic components
  • oleic acid ethyl ester linoleic acid ethyl ester
  • dihydrocrefeninic acid ethyl ester dihydrocrefeninic acid ethyl ester
  • docosahexaenoic acid ethyl ester docosahexaenoic acid ethyl ester
  • conventional gastritis-gastric ulcer therapeutic components When prepared and administered in combination, it was shown that gastritis-gastric ulcer inhibition rate was increased by 20% or more than administration of the conventional therapeutic ingredients alone.
  • the fatty acid or ester compound thereof according to the present invention has an excellent effect of protecting the gastric wall by inhibiting gastritis-gastric ulcer lesions, and significantly increases the lesion suppression effect of gastritis-gastric ulcer when used with existing therapeutic ingredients. It can be usefully used as a protective agent and gastrointestinal disease treatment.
  • the co-administration of the fatty acid compound according to the present invention with other effective drugs has an effect of inhibiting gastrointestinal diseases such as gastritis and / or gastric ulcers compared with the use of these effective drugs with the extract of the mycelium mycelium mycelium culture (HEAC) cultured in Ingeria mugwort medium.
  • HEAC mycelium mycelium mycelium culture
  • the conventional gastrointestinal disease treatment in combination with the fatty acid-based compound according to the present invention was shown to be more than 10% more effective in suppressing the gastrointestinal disease than when co-administered with HEAC.
  • Group 2 (Comparative Group 1): Omeprazole was suspended in 3 mL of saline solution and administered orally at a dose of 40 mg / kg.
  • Group 3 (Comparative Group 2): After removing the coating from styrene tablet (Dong-A Pharmaceutical), the main component was suspended in 3 mL of saline solution and administered orally at a dose of 40 mg / kg.
  • Group 4 (Test Group 1): As a fatty acid compound, linoleic acid ethyl ester was suspended in 3 mL of saline solution and administered orally at a dose of 40 mg / kg.
  • Group 5 A compound prepared by mixing linoleic acid ethyl ester and omeprazole in a 1: 1 ratio as a fatty acid compound, suspended in 3 mL of saline solution and administered orally at a dose of 40 mg / kg.
  • mice After 24 hours, eight rats were sacrificed in each group, and the stomach was removed by the method described in Example 2 to measure the degree of ulceration. The remaining mice received a second oral dose of sample.
  • mice After 48 hours, eight rats were sacrificed in each group, and the stomach was removed to measure the degree of ulceration. The remaining mice received a third oral dose of sample.
  • linoleic acid ethyl ester which is a kind of fatty acid-based compound according to the present invention, showed a treatment rate of 51.5% after 24 hours after the occurrence of gastrointestinal disease when administered alone, and after 72 hours. It shows a 85% treatment rate, which is superior to conventional gastrointestinal disorders treatments (omeprazole: 37% / 71.1%, styrene: 44.7% / 69.5%), and is higher when combined with conventional gastrointestinal disorders. The effect was shown.
  • the fatty acid or ester compound thereof according to the present invention protects the gastric wall and has an excellent effect of inhibiting gastritis-gastric ulcer lesions, and also has a therapeutic effect when gastritis-gastric ulcers occur, and when used with conventional therapeutic ingredients, gastric-gastric ulcer lesions Significantly increase the inhibitory effect can be useful as a gastric wall protection and gastrointestinal disease treatment.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne une composition pour protéger la paroi stomacale et pour prévenir ou traiter des troubles gastriques, contenant un composant actif comprenant un composé de la série des acides gras qui est efficace dans la protection de la paroi stomacale et le traitement des troubles gastriques.
PCT/KR2010/002105 2009-04-06 2010-04-06 Composition pour prévenir ou traiter des troubles gastriques contenant un composant actif comprenant un composé de la série des acides gras Ceased WO2010117194A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020090029405A KR20100111040A (ko) 2009-04-06 2009-04-06 지방산 계열 화합물을 유효성분으로 함유하는 위장 질환 예방 또는 치료용 조성물
KR10-2009-0029405 2009-04-06

Publications (2)

Publication Number Publication Date
WO2010117194A2 true WO2010117194A2 (fr) 2010-10-14
WO2010117194A3 WO2010117194A3 (fr) 2011-03-17

Family

ID=42936709

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2010/002105 Ceased WO2010117194A2 (fr) 2009-04-06 2010-04-06 Composition pour prévenir ou traiter des troubles gastriques contenant un composant actif comprenant un composé de la série des acides gras

Country Status (2)

Country Link
KR (1) KR20100111040A (fr)
WO (1) WO2010117194A2 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014129384A1 (fr) * 2013-02-21 2014-08-28 国立大学法人京都大学 Agent de protection du tractus intestinal contenant un acide gras hydroxylé
CN114126602A (zh) * 2019-05-27 2022-03-01 阿勒思科公司 用于治疗胃粘膜、糖尿病和高血糖水平的包含十六烷化脂肪酸的组合物
US12246036B2 (en) 2017-08-02 2025-03-11 Pharmanutra S.P.A. Composition for use in the prevention and in the treatment of iron deficiency
US12297406B2 (en) 2019-05-27 2025-05-13 Alesco S.R.L. Method for preparing a composition comprising cetylated fatty acids
US12383525B2 (en) 2019-05-27 2025-08-12 Pharmanutra S.P.A. Compositions comprising cetylated fatty acids and use thereof for the treatment of arthritis and joint inflammatory conditions

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2848251B1 (fr) 2013-09-12 2017-04-19 King Saud University Extraits et composés isolés à partir de Cakile arabica pour le traitements des ulcers
CN105232506A (zh) * 2015-11-04 2016-01-13 温州医科大学 丁酸及其盐在制备治疗或预防胃溃疡药物中的应用
CN105769840B (zh) * 2016-04-01 2018-06-29 温州医科大学 乙酸及其盐的应用
KR20180051736A (ko) * 2016-11-08 2018-05-17 차의과학대학교 산학협력단 오메가-3 폴리불포화지방산을 활성 성분으로 포함하는 헬리코박터 파일로리 유래 위염 및 위암에 대한 활성을 가지는 조성물
KR102625873B1 (ko) * 2023-01-27 2024-01-16 한국생명공학연구원 근감소증 예방, 치료 또는 개선용 조성물 및 근감소증을 진단하는 방법

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ205076A (en) * 1982-08-09 1985-04-30 Univ California Protecting and healing gastro-duodenal mucosa and the liver of mammals using a fatty acid
NZ281878A (en) * 1994-04-01 1997-02-24 Abbott Lab Nutritional product for enteral feeding containing indigestible carbohydrate, an oil blend and optionally protein and other nutrients; used to treat colitis
US5660842A (en) * 1994-10-04 1997-08-26 Bristol-Myers Squibb Company Inhibition of helicobacter
JPH10130161A (ja) * 1996-09-06 1998-05-19 Otsuka Pharmaceut Co Ltd ヘリコバクター・ピロリに対する組成物
KR100624102B1 (ko) * 2004-02-06 2006-09-18 주식회사 코시스바이오 버섯 추출물을 포함하는 항헬리코박터 조성물

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014129384A1 (fr) * 2013-02-21 2014-08-28 国立大学法人京都大学 Agent de protection du tractus intestinal contenant un acide gras hydroxylé
CN104994846A (zh) * 2013-02-21 2015-10-21 国立大学法人京都大学 含有羟基化脂肪酸的肠道保护剂
US20160000739A1 (en) * 2013-02-21 2016-01-07 Kyoto University Intestinal tract-protecting agent containing hydroxylated fatty acid
US9539229B2 (en) 2013-02-21 2017-01-10 Kyoto University Intestinal tract-protecting agent containing hydroxylated fatty acid
CN104994846B (zh) * 2013-02-21 2018-01-19 国立大学法人京都大学 含有羟基化脂肪酸的肠道保护剂
US12246036B2 (en) 2017-08-02 2025-03-11 Pharmanutra S.P.A. Composition for use in the prevention and in the treatment of iron deficiency
CN114126602A (zh) * 2019-05-27 2022-03-01 阿勒思科公司 用于治疗胃粘膜、糖尿病和高血糖水平的包含十六烷化脂肪酸的组合物
US20220226274A1 (en) * 2019-05-27 2022-07-21 Alesco S.R.L. Compositions comprising cetylated fatty acids for use in the treatment of gastric mucosa, diabetes and high blood glucose levels
US12297406B2 (en) 2019-05-27 2025-05-13 Alesco S.R.L. Method for preparing a composition comprising cetylated fatty acids
US12383525B2 (en) 2019-05-27 2025-08-12 Pharmanutra S.P.A. Compositions comprising cetylated fatty acids and use thereof for the treatment of arthritis and joint inflammatory conditions

Also Published As

Publication number Publication date
WO2010117194A3 (fr) 2011-03-17
KR20100111040A (ko) 2010-10-14

Similar Documents

Publication Publication Date Title
WO2010117194A2 (fr) Composition pour prévenir ou traiter des troubles gastriques contenant un composant actif comprenant un composé de la série des acides gras
WO2017078499A2 (fr) Composition pour la prévention ou le traitement d'une maladie neuroinflammatoire, contenant un inhibiteur de la protéine tyrosine phosphatase
WO2013172640A1 (fr) Composition présentant une activité d'induction de protéines de choc thermique et contenant un composé isolé à partir d'eucommia ulmoides
WO2019182276A1 (fr) Préparation d'une association de produits pharmaceutiques comprenant de l'ézétimibe et de la rosuvastatine
WO2013122345A1 (fr) Forme galénique améliorée contenant un extrait d'écorce de liriodendron tulipifera en tant qu'ingrédient actif
WO2014042426A1 (fr) Composition comprenant de la saikosaponine a, de la berbérine et de la licoisoflavone b pour la prévention ou le traitement de maladies gastriques
WO2013122344A1 (fr) Composition pharmaceutique contenant en tant qu'ingrédient actif un extrait provenant de l'écorce de liriodendron tulipifera
WO2016175589A2 (fr) Composition pharmaceutique pour la prévention ou le traitement de maladies respiratoires, contenant un extrait de mélange de plantes médicinales
WO2023022569A1 (fr) Méthode de traitement de maladies immunitaires au moyen d'un inhibiteur de la calcineurine et de cellules souches
WO2015083996A1 (fr) Forme posologique pharmaceutique destinée au traitement d'une leucémie myéloïde chronique, contenant un extrait d'écorce de liriodendron tulipifera l. comme principe actif
KR101085970B1 (ko) 쿠마린 유도체를 유효성분으로 함유하는 위장 질환 예방 또는 치료용 조성물
WO2018199636A1 (fr) Formulation combinée comprenant un inhibiteur de la hmg-coa réductase et un bloqueur des canaux calciques
WO2023171894A1 (fr) Composition pharmaceutique comprenant du docétaxel ou un sel pharmaceutiquement acceptable de celui-ci et son procédé de préparation
WO2023068839A1 (fr) Comprimé enrobé de film présentant une stabilité améliorée contenant du montélukast ou son sel pharmaceutiquement acceptable et de la lévocétirizine ou son sel pharmaceutiquement acceptable
WO2022139529A1 (fr) Composition pour la prévention, l'amélioration ou le traitement de la gastrite ou de l'ulcère gastroduodénal comprenant un extrait de cinnamomum cassia, une fraction dudit extrait, un isolat de ladite fraction ou des composés isolés à partir de ladite fraction
WO2018030559A1 (fr) Préparation combinée de comprimé monocouche contenant du telmisartan
WO2013025004A2 (fr) Composition pharmaceutique pour prévenir ou traiter le cancer comprenant un extrait de radix lithospermi seu arnebiae en tant que substance active
WO2020209475A1 (fr) Composition pour administration par voie orale présentant des propriétés de libération contrôlée, comprenant un complexe de minéraux argileux, procédé pour sa préparation et procédé de régulation des propriétés de libération
WO2018026150A1 (fr) Composition pharmaceutique pour la prévention ou le traitement de maladies neurodégénératives
WO2024085698A1 (fr) Composition pharmaceutique pour la prévention ou le traitement d'une maladie intestinale inflammatoire comprenant un inhibiteur de glycogène phosphorylase (pygl) en tant que principe actif
WO2016032127A2 (fr) Nouveaux composés présentant des activités antioxydantes et anti-inflammatoires en raison de la concurrence avec lps pour se lier à tlr4, et leur utilisation médicale
WO2015102205A1 (fr) Composition pharmaceutique permettant de prévenir ou de traiter le cancer et contenant un inhibiteur des protéasomes et du lopéramide en tant que principes actifs
WO2023048511A1 (fr) Composition pharmaceutique pour la prévention ou le traitement du cancer comprenant un inhibiteur de la carnitine-acylcarnitine translocase et un inhibiteur de la carnitine octanoyltransférase
WO2015111971A1 (fr) Composition pharmaceutique contenant un ligand gpr119 comme principe actif pour prévenir ou traiter une stéatose hépatique non alcoolique
WO2023128464A1 (fr) Composition pharmaceutique pour prévenir ou traiter le cancer, comprenant un inhibiteur des transporteurs de la carnitine acylcarnitine et un inhibiteur de la bêta-oxydation peroxisomale

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10761855

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 10761855

Country of ref document: EP

Kind code of ref document: A2