WO2010117194A2 - Composition for preventing or treating gastric disorders containing an active component comprising a fatty acid series compound - Google Patents

Composition for preventing or treating gastric disorders containing an active component comprising a fatty acid series compound Download PDF

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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
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acid
ethyl ester
acid ethyl
ester
group
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PCT/KR2010/002105
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French (fr)
Korean (ko)
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WO2010117194A3 (en
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최원식
장도연
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대원제약주식회사
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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
    • A61K31/185—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.

Abstract

The present invention relates to a composition for protecting the stomach wall and for preventing or treating gastric disorders, containing an active component comprising a fatty acid series compound which is effective in protecting the stomach wall and treating gastric disorders.

Description

지방산 계열 화합물을 유효성분으로 함유하는 위장 질환 예방 또는 치료용 조성물Composition for preventing or treating gastrointestinal diseases, containing fatty acid compounds as active ingredients
본 발명은 위장 질환 치료 효과를 갖는 지방산 계열 화합물을 유효성분으로 함유하는 위장 질환 예방 및/또는 치료용 조성물에 관한 것이다.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.
본 발명은 위장 질환 치료 효과를 갖는 지방산 계열 화합물을 유효성분으로 함위는 식도를 통하여 들어온 음식물을 저장하고 소화되기 쉽게 잘게 부수며, 십이지장으로 음식물을 보내는 것을 조절하여 췌장효소의 분비와 조화를 이루어 효율적인 소화와 흡수가 되도록 하는 장기이다. 위는 음식물이 들어오면 이를 소화시키기 위해 강한 산인 위산을 분비하는데, 이때 점막보호층이 위산에 의해 위점막이 손상받지 않도록 작용한다. 사람의 위장관계 기능에 악영향을 미치는 요인은 그 성질이 극히 다양하다. 이와 같은 장해는 상부 위장관, 하부 위장관 또는 두 부분 모두에서 발생할 수 있으며, 유전적, 생리학적, 환경적 및 정신적 요인을 포함하여 광범위한 위장 장해 요인이 있다. 상부 위장관의 만성 질환 중에는 위염 및 위궤양이 포함되어 있으며, 여러 종류의 원인에 의해 위산의 분비가 항진되거나 위점막 보호층이 손상되었을 때 염증이 생기게 된다. 이 염증성 병변이 위점막에 한정되어 있을 때를 위염(gastritis), 위점막을 뚫고 점막하 조직과 근육층까지 궤양을 형성했을 때를 위궤양(gastric ulcer)이라 한다. 또한 십이지장에서의 궤양을 십이지장궤양(duodenal ulcer)이라고 하며, 위궤양과 십이지장궤양을 소화성 궤양(peptic ulcer)으로 통칭하고 있다. 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. 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.
위염 및 소화성 궤양 등의 위장 질환을 치료하기 위하여 사용되는 약물로는 궤양을 촉진시키고 재발시키는 인자인 위산, 펩신, 스트레스 등을 감소시키기 위한 약물이 주로 사용되고 있으며, 그 중 위산의 과잉분비를 억제하는 약물이 가장 많이 사용되고 있다. 기존의 위염 및 소화성 궤양의 치료제로는 과다한 위 분비액을 중화시키는 제산제(antacid), 위산 분비를 억제하는 히스타민 H2 수용체 길항제와 프로톤 펌프 저해제(proton pump inhibitor), 소화액에 대한 위 내막의 내성을 증가시키고 산 분비를 억제할 수 있는 프로스타글란딘(prostaglandin) 계열 약제, 또는 위점막 보호제 등이 있다. 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. And prostaglandin-based drugs or gastric mucosa protective agents capable of inhibiting acid secretion.
상기 약물 중 제산제는 근본적인 치료가 아닌 일시적인 속효성을 위한 것으로, 위내의 pH를 상승시켜 펩신의 활성을 저하시킴으로써 약효를 나타낸다. 그러나, 무기물질 투여에 의해 변비, 설사, 대사성 알칼로시스(alkalosis), 요로결석증 등과 같은 부작용이 보고되어 있으며, 최근에는 제산제에 의한 산반동(acid rebound) 현상 등이 문제시되고 있다.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. However, 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.
가장 널리 사용되고 있는 H2 수용체 길항제인 시메티딘(cimetidine)은, 위점막 내의 히스타민 수용체를 차단하여 히스타민 분자를 위세포가 차단함으로써 히스타민 분자가 위세포로 하여금 산의 분비 신호를 하지 못하도록 작용한다. 소화성 궤양의 본격적 치료는 상기 시메티딘이 1977년 발매되면서부터 시작되었으며, 여러 종류의 유도체가 개발되었다. 그 중 라니티딘 (ranitidine), 파모티딘(famotidine), 록사티딘(roxatidine), 니자티딘 (nizatidine) 등은 치료기간의 단축을 특징으로 임상에서 우수한 항궤양 효과를 나타내고 있으나, 약물투여 중지 후 높은 재발율이 나타나는 단점이 있다. 또한, 시메티딘은 호중구 감소증 등의 부작용을 비롯하여 약물상호작용까지 나타내므로 사용을 기피하는 현상을 보이며, 가장 최근의 약인 라니티딘이나 파모티딘은 장기간 사용 시 약효가 크게 감소되는 현상이 목격되고 있다.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. In addition, 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.
또한, 프로톤 펌프 저해제로는 오메프라졸(omeprazole), 란소프라졸 (lansoprazol), 판토프라졸(pantoprazole) 등이 있으며, 위벽세포에서의 산 분비를 최종단계에서 저해하여 강력한 산 분비억제 효과를 나타내는 것으로 알려져 있다. 그 외에도 미소프로스톨(misoprostol), 애엽(Artemisiae argyi Folium) 추출물, 테프레논(teprenone) 등과 같은 프로스타글란딘 생합성 촉진계 위점막 질환 치료제가 있으며, 가스트린 수용체 저해제인 레바미피드(rebamipide) 등이 있다. 그러나, 이들 약제에 의한 궤양치유 환자에서도 재발율은 감소되지 않고 있으며, 연변, 설사, 발열, 두통, 피로감 등의 부작용이 보고되고 있다.In addition, 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. In addition, there are 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. However, 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.
따라서, 부작용이 적은 성분의 위장 질환 치료제의 개발이 요구된다.Therefore, there is a need for the development of a gastrointestinal disease therapeutic agent with fewer side effects.
본 발명의 목적은 지방산 및 지방산 에스테르, 또는 이의 약학적으로 허용되는 염을 유효성분으로 함유하는 위장 질환 예방 및/또는 치료용 조성물을 제공하는 것이다. It is an object of the present invention to provide a composition for the prevention and / or treatment of gastrointestinal diseases, which contains a fatty acid and fatty acid ester, or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 목적은 지방산 및 지방산 에스테르, 또는 이의 약학적으로 허용되는 염(제1 성분)과, H2 수용체 길항제, 프로톤 펌프 저해제, 가스트린 수용체 저해제, 및 위점막 보호제(위점막 질환 치료제) 등으로 이루어진 군으로부터 선택되는 1종 이상(제2 성분)을 포함하는 위장 질환 예방 및/또는 치료용 복합 제제 조성물을 제공하는 것이다.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.
상기 목적을 달성하기 위하여 본 발명은 지방산 및 지방산 에스테르, 또는 이의 약학적으로 허용되는 염을 유효성분으로 함유하는 위장 질환 예방 및/또는 치료용 조성물을 제공한다. In order to achieve the above object, 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.
또한, 본 발명은 지방산 및 지방산 에스테르, 또는 이의 약학적으로 허용되는 염(제1 성분)과, H2 수용체 길항제, 프로톤 펌프 저해제, 가스트린 수용체 저해제, 및 위점막 보호제(위점막 질환 치료제) 등으로 이루어진 군으로부터 선택되는 1종 이상(제2 성분)을 포함하는 위장 질환 예방 및/또는 치료용 복합 제제 조성물을 제공한다.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.
나아가, 본 발명은 지방산 및 지방산 에스테르, 또는 이의 약학적으로 허용되는 염을 유효성분으로 함유하는 위벽 보호용 조성물을 제공한다.Furthermore, 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.
또한, 본 발명은 지방산 및 지방산 에스테르, 또는 이의 약학적으로 허용되는 염(제1 성분)과, H2 수용체 길항제, 프로톤 펌프 저해제, 가스트린 수용체 저해제, 및 위점막 보호제(위점막 질환 치료제) 등으로 이루어진 군으로부터 선택되는 1종 이상(제2 성분)을 포함하는 위벽 보호용 조성물을 제공한다.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.
본 발명에 따른 지방산 또는 이의 에스테르 화합물은 위벽의 보호 및/또는 치료 효과가 우수하므로 위장 질환 치료에 유용할 것으로 기대되며, 특히, 위산 제거 효과가 있는 다른 유효성분과 함께 사용되는 경우 매우 유의적인 상승 효과가 있을 것으로 기대된다.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.
도 1은 인진쑥 배지에서 배양된 노루궁뎅이 버섯 균사체 배양물(HEAC)의 메틸렌클로라이드 추출물의 기체 크로마토그래피 결과를 보여주는 것이다.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.
도 2는 본 발명에 따른 지방산 계열 화합물의 투여 후 시간에 따른 위 병변율을 나타내는 그래프이다.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.
도 3은 본 발명에 따른 지방산 계열 화합물의 투여 후 시간에 따른 위 병변의 치료율을 나타내는 그래프이다.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.
이하, 본 발명을 상세하게 설명한다.EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail.
본 발명은 포화 지방산, 상기 포화 지방산의 알킬 에스테르 화합물, 불포화 지방산 및 상기 불포화 지방산의 알킬 에스테르 화합물로 이루어진 군으로부터 선택되는 1종 이상의 화합물, 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 함유하는 위벽 보호, 위장 질환의 예방 또는 치료용 조성물을 제공한다.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. Provided are compositions for protection, prevention or treatment of gastrointestinal diseases.
또한, 본 발명은 포화 지방산, 상기 포화 지방산의 알킬 에스테르 화합물, 불포화 지방산 및 상기 불포화 지방산의 알킬 에스테르 화합물로 이루어진 군으로부터 선택되는 1종 이상의 화합물(제1 성분)과; H2 수용체 길항제, 프로톤 펌프 저해제, 가스트린 수용체 저해제, 위점막 보호제 및 인진쑥 배지에서 배양된 노루궁뎅이 버섯 균사체(Hericium erinaceum Hypha Cultivated with Artemisia capillaries, HEAC) 추출물로 이루어진 군에서 선택된 1종 이상(제2 성분)을 포함하는 위벽 보호, 위장 질환의 예방 또는 치료용 조성물을 제공한다.In addition, 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.
본 발명에 따른 조성물에 있어서, 상기 포화 지방산은 탄소수 4 내지 40개, 바람직하게는 4 내지 14 또는 20 내지 40개의 포화 지방산을 사용할 수 있으며, 예컨대, 부티르산(Butyric acid), 카프로산(Caproic acid), 카프릴산(Caprylic acid), 카프르산(Capric acid), 라우르산(Lauric acid), 미리스트산(Myristic acid), 테트라메틸데카노산(Tetramethyldecanoic acid), 팔미트산(Palmitic acid), 스테아르산(Stearic acid), 디하이드로스테르쿨린산(Dihydrosterculic acid), 튜베르큘로스테아르산(Tuberculostearic acid), 아라키드산(Arachidic acid), 베헨산(Behenic acid), 리그노세르산(Lignoceric acid), 세로트산(Cerotic acid), 몬타닌산(Montanic acid), 멜리스산(Melissic acid), 및 코리노미콜산(Corynomycolic acid)로 이루어진 군으로부터 선택되는 1종 이상의 것일 수 있다.In the composition according to the present invention, 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. , Caprylic acid, capric acid, lauric acid, myristic acid, tetramethyldecanoic acid, palmitic acid, Stearic acid, Dihydrosterculic acid, Tuberculostearic acid, Arachidic acid, Behenic acid, Lignoceric acid), cerotic acid, montanic acid, melissic acid, and corinomycolic acid.
본 발명에 따른 조성물에 있어서, 상기 불포화 지방산은 탄소수 8 내지 30개, 바람직하게는 8 내지 16 또는 20 내지 30개의 불포화 지방산을 사용할 수 있으며, 예컨대, 디하이드로메트리카리아산(Dehydromatricaria acid), 운데세노산(Undecenoic acid), 히드노카르프산(Hydnocarpic acid), 팔미톨레산(Palmitoleic acid), 차울무그르산(Chaulmoogric acid), 말발산(Malvalic acid), 올레산(Oleic acid), 리시놀레산(Ricinoleic acid), 박센산(Vaccenic acid), 리놀레산(Linoleic acid), 크레페닌산(Crepenynic acid), 디하이드로크레페닌산(Dehydrocrepenynic acid), 리놀렌산(Linolenic acid), 스테아리돈산(Stearidonic acid), 스테르쿨린산(Sterculic acid), 가돌레산(Gadoleic acid), DHLA(Dihomo-γ-Linolenic acid), 에이코사테트라에노산(Eicosatetraenoic acid), 아라키돈산(Arachidonic acid), 에이코사펜타에노산(Eicosapentaenoic acid, EPA), 에루스산(Erucic acid), 치코르산(Cichoric acid), 도코사펜타에노산(Docosapentaenoic acid, DPA), 도코사헥사에노산(Docosahexaenoic acid, DHA), 및 네르본산(Nervonic acid)으로 이루어진 군으로부터 선택되는 1종 이상의 것일 수 있다. In the composition according to the present invention, 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-γ-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. pentamethyl the group consisting of acid (Docosapentaenoic acid, DPA), acid to docosahexaenoic (Docosahexaenoic acid, DHA), and a tunnel acid (Nervonic acid) to.
바람직하게는 상기 지방산으로서 올레산, 리놀레산, 디하이드로크레페닌산, 도코사헥사에노산 및 아라키돈산으로 이루어진 군으로부터 선택되는 1종 이상을 사용할 수 있으며, 가장 바람직하게는 리놀레산을 사용할 수 있다.Preferably, 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.
본 발명에 따른 조성물에 있어서, 상기 알킬 에스테르 화합물은 탄소수 1 내지 4의 알킬기, 바람직하게는 메틸기 또는 에틸기, 더욱 바람직하게는 에틸기가 결합된 지방산의 에스테르 화합물일 수 있다. In the composition according to the present invention, 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.
보다 바람직한 일례에서, 상기 포화지방산의 알킬 에스테르 화합물은 탄소수 4 내지 40개, 바람직하게는 4 내지 14 또는 20 내지 40개의 포화 지방산의 메틸 또는 에틸 에스테르 화합물로 이루어진 군으로부터 선택되는 1종 이상의 화합물일 수 있고, 상기 불포화 지방산의 알킬 에스테르 화합물은 탄소수 8 내지 30개, 바람직하게는 8 내지 16 또는 20 내지 30개의 불포화 지방산의 메틸 또는 에틸 에스테르 화합물로 이루어진 군으로부터 선택되는 1종 이상의 화합물일 수 있다.In a more preferred example, 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.
예컨대, 포화 지방산의 에스테르 화합물은 부티르산 에틸 에스테르(Butyric acid ethyl ester), 카프로산 에틸 에스테르(Caproic acid ethyl ester), 카프릴산 에틸 에스테르(Caprylic acid ethyl ester), 카프르산 에틸 에스테르(Capric acid ethyl ester), 라우르산 에틸 에스테르(Lauric acid ethyl ester), 미리스트산 에틸 에스테르(Myristic acid ethyl ester), 테트라메틸데카노산 에틸 에스테르(Tetramethyl decanoic acid ethyl ester), 팔미트산 에틸 에스테르(Palmitic acid ethyl ester), 스테아르산 에틸 에스테르(Stearic acid ethyl ester), 디하이드로스테르쿨린산 에틸 에스테르(Dihydrosterculic acid ethyl ester), 튜베르큘로스테아린산 에틸 에스테르(Tuberculostearic acid ethyl ester), 아라키드산 에틸 에스테르(Arachidic acid ethyl ester), 베헨산 에틸 에스테르(Behenic acid ethyl ester), 리그노세르산 에틸 에스테르(Lignoceric acid ethyl ester), 세로트산 에틸 에스테르(Cerotic acid ethyl ester), 몬타닌산 에틸 에스테르(Montanic acid ethyl ester), 멜리스산 에틸 에스테르(Melissic acid ethyl ester) 및 코리노미콜산 에틸 에스테르(Corynomycolic acid ethyl ester)로 이루어진 군으로부터 선택되는 1종 이상의 것일 수 있으며, 상기 불포화 지방산의 에스테르 화합물은 데카-2-엔-4,6,8-트리이노산 에틸 에스테르((E)-deca-2-en-4,6,8-triynoic acid ethyl ester), 운데세노산 에틸 에스테르(Undecenoic acid ethyl ester), 히드노카르프산 에틸 에스테르(Hydnocarpic acid ethyl ester), 팔미톨레산 에틸 에스테르(Palmitoleic acid ethyl ester), 차울무그르산 에틸 에스테르(Chaulmoogric acid ethyl ester), 말발산 에틸 에스테르(Malvalic acid ethyl ester), 올레산 에틸 에스테르(Oleic acid ethyl ester), 리시놀레산 에틸 에스테르(Ricinoleic acid ethyl ester), 박센산 에틸 에스테르(Vaccenic acid ethyl ester), 리놀레산 에틸 에스테르(Linoleic acid ethyl ester), 크레페닌산 에틸 에스테르(Crepenynic acid ethyl ester), 디하이드로크레페닌산 에틸 에스테르(Dehydrocrepenynic acid ethyl ester), 리놀렌산 에틸 에스테르(Linolenic acid ethyl ester), 스테아리돈산 에틸 에스테르(Stearidonic acid ethyl ester), 스테르쿨린산 에틸 에스테르(Sterculic acid ethyl ester), 가돌레산 에틸 에스테르(Gadoleic acid ethyl ester), 에이코사테트라에노산 에틸 에스테르(Eicosatetraenoic acid ethyl ester), 아라키돈산 에틸 에스테르(Arachidonic acid ethyl ester), 에이코사펜타에노산 에틸 에스테르(Eicosapentaenoic acid ethyl ester), 에루스산 에틸 에스테르(Erucic acid ethyl ester), 치코르산 에틸 에스테르(Cichoric acid ethyl ester), 도코사펜타에노산 에틸 에스테르(Docosapentaenoic acid ethyl ester), 도코사헥사에노산 에틸 에스테르(Docosahexaenoic acid ethyl ester) 및 네르본산 에틸 에스테르(Nervonic acid ethyl ester)로 이루어진 군으로부터 선택되는 1종 이상의 것일 수 있다.For example, 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 corynomycolic acid ethyl ester It may be one or more, the ester compound of the unsaturated fatty acid is deca-2-ene-4,6,8-triino acid ethyl ester ((E) -deca-2-en-4,6,8-triynoic acid ethyl ester, Undecenoic acid ethyl ester, Hydnocarpic acid ethyl ester, Palmitoleic acid ethyl ester, Chaulmoogric acid ethyl ester ester, Malvalic acid ethyl ester, Oleic acid ethyl ester, Ricinoleic acid ethyl ester, Vaccenic acid eth yl ester, linoleic acid ethyl ester, crepenynic acid ethyl ester, dehydrocrepenynic acid ethyl ester, linolenic acid ethyl ester, stearic acid Stearonic Acid Ethyl Ester, Sterculic Acid Ethyl Ester, Gadoleic Acid Ethyl Ester, Eicosatetraenoic Acid Ethyl Ester, Arachidonic Acid Arachidonic acid ethyl ester, Eicosapentaenoic acid ethyl ester, Erucic acid ethyl ester, Chicoric acid ethyl ester, Docosapenta Docosapentaenoic acid ethyl ester, Docosahexaenoic acid ethyl ester ter) and Nervonic acid ethyl ester (Nervonic acid ethyl ester) may be one or more selected from the group consisting of.
바람직하게는 상기 지방산의 에스테르 화합물로서 올레산 에틸 에스테르, 리놀레산 에틸 에스테르, 디하이드로크레페닌산 에틸 에스테르, 도코사헥사에노산 에틸 에스테르 및 아라키돈산 에틸 에스테르로 이루어진 군으로부터 선택되는 1종 이상을 사용할 수 있으며, 가장 바람직하게는 리놀레산 에틸 에스테르를 사용할 수 있다.Preferably, 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.
본 발명에 따른 지방산 또는 이의 에스테르 화합물은 위벽을 보호하여 위염-위궤양의 병변을 억제하는 효과가 뛰어나고(표 2 및 3 참조), 위염-위궤양 발생시 치료효과도 종래 위장질환 치료제의 효과보다도 뛰어난 것으로 나타났다(표 17 참조). 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).
또한, 상기 지방산 및/또는 이의 에스테르 화합물을 통상의 위장질환 치료제, 예컨대, 위산조절 효과를 갖는 H2 수용체 길항제 및/또는 프로톤 펌프 저해제 및/또는 가스트린 수용체 저해제 및/또는 위점막 보호제(위점막 질환 치료제) 등과 병용하는 경우, 위산조절 효과와 위벽 보호 효과를 동시에 얻을 수 있기 때문에, 보다 탁월한 위장 질환 예방 및/또는 치료 효과를 나타낼 수 있다. 아래의 실시예에서 확인되는 바와 같이, 라니티딘, 시메티딘, 파모티딘, 록사티딘, 니자티딘 등의 H2 수용체 길항제 또는 오메프라졸, 에스오메프라졸, 란소프라졸, 판토프라졸, 라베프라졸, 레바프라잔, 일라프라졸 등의 프로톤 펌프 저해제, 또는 레바미피드 등의 가스트린 수용체 저해제, 또는 미소프로스톨, 애엽 추출물 등의 위점막 보호제(위점막 질환 치료제), 인진쑥 배지에서 배양된 노루궁뎅이 버섯 균사체(Hericium erinaceum Hypha Cultivated with Artemisia capillaries, HEAC) 추출물을 본 발명의 지방산 및/또는 이의 에스테르 화합물과 혼합하여 복합제제로 투여하는 경우가, 상기 약물을 단독 투여하는 경우보다 위염 및/또는 위궤양 등의 위장질환 억제 효과와 ED50값이 현저하게 개선되는 것으로 나타났다(표 12 내지 15 참조).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. As confirmed in the Examples below, 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) When Cultivated with Artemisia capillaries (HEAC) extract is mixed with the fatty acid of the present invention and / or its ester compound and administered as a co-formulation, the effect of inhibiting gastrointestinal diseases such as gastritis and / or gastric ulcer and ED is higher than that of the drug alone. 50 values were found to be significantly improved (see Tables 12-15).
따라서, 본 발명에 따른 지방산 또는 이의 에스테르 화합물은 위벽을 보호하여 위염-위궤양의 병변을 억제하는 효과가 뛰어나고, 위염-위궤양 발생시 치료효과도 뛰어나며, 기존의 치료성분과 함께 사용할 때 위염-위궤양의 병변 억제효과를 유의적으로 상승시키므로 위벽 보호 및 위장 질환 치료제로서 유용하게 사용될 수 있다.Therefore, 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.
본 발명의 조성물이 예방 및/또는 치료 효과를 갖는 위장 질환은 역류성 식도염, 위염, 십이지장염, 위 궤양, 십이지장 궤양, 비스테로이드성 항염증 약물(NSAID)과 연관된 소화 장애, 비궤양 소화불량, 위식도 역류질환, 가스트린종, 급성 상부 위장 출혈, 스트레스 궤양화, 헬리코박터 파일로리 감염, Zollinger-Ellison 증후군(ZES), Werner's 증후군, 및 전신 비만세포증으로 이루어진 군에서 선택된 것일 수 있으나 이에 제한되는 것은 아니다.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.
본 발명에 따른 조성물에 있어서, 제2 성분으로 사용 가능한 H2 수용체 길항제는 시메티딘, 라니티딘, 파모티딘, 록사티딘, 니자티딘, 및 이들의 약학적으로 허용 가능한 염, 이성질체 및 이성질체의 염 등으로 이루어진 군에서 1종 이상 선택된 것일 수 있다.In the composition according to the present invention, 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.
본 발명에 따른 조성물에 있어서, 제2 성분으로 사용 가능한 프로톤 펌프 저해제는 오메프라졸, 에스오메프라졸, 란소프라졸, 판토프라졸, 라베프라졸, 레바프라잔, 일라프라졸, 파리프라졸, 레미노프라졸, 및 이들의 약학적으로 허용 가능한 염, 이들의 거울상이성질체 및 거울상이성질체의 약학적으로 허용 가능한 염으로 이루어진 군에서 1종 이상 선택된 것일 수 있다.In the composition according to the present invention, 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.
본 발명에 따른 조성물에 있어서, 제2 성분으로 사용 가능한 가스트린 수용체 저해제는 레바미피드 및 이의 약학적으로 허용 가능한 염으로 이루어진 군에서 1종 이상 선택된 것일 수 있다.In the composition according to the present invention, 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.
본 발명에 따른 조성물에 있어서, 제2 성분으로 사용 가능한 위점막 보호제(위점막 질환 치료제)는 미소프로스톨, 이의 약학적으로 허용 가능한 염, 및 애엽(Artemisiae Argyi Folium) 추출물(예컨대, 80 내지 100 v/v% 에탄올 추출물)로 이루어진 군에서 1종 이상 선택된 것일 수 있으나, 이에 한정되는 것은 아니다. In the composition according to the present invention, 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.
상기 제2 성분으로 사용 가능한 인진쑥 배지에서 배양된 노루궁뎅이 버섯 균사체(Hericium erinaceum Hypha Cultivated with Artemisia capillaries, HEAC) 추출물은 인진쑥 배지에서 배양된 노루궁뎅이 버섯 균사체를 물, 탄소수 1 내지 5의 알코올(예컨대, 25 내지 100 v/v%), 헥산, 클로로포름, 염화메틸렌, 아세토니트릴, 아세톤 및 에틸아세테이트로 이루어진 군에서 선택된 1종 이상의 용매로 추출하여 얻어진 것이거나, 상기 얻어진 추출물에 탄소수 1 내지 5의 알코올(예컨대, 25 내지 100 v/v%), 헥산, 염화메틸렌, 및 에틸아세테이트로 이루어진 군에서 선택된 1종 이상을 추가로 가하여 얻어지는 분획물일 수 있다. 상기 추출방법은 식물 추출물 제조에 통상적으로 사용되는 모든 방법에 의할 수 있으며, 예컨대, 교반추출, 열수추출 등에 의할 수 있고, 추출 후 통상적 방법으로 여과 및/또는 농축될 수 있다. 이 외의 인진쑥 배지에서 배양된 노루궁뎅이 버섯 균사체 추출물에 관련된 내용은 한국특허출원 제10-2007-0108131호에 기재된 바에 따른다.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.
본 발명에 따른 조성물이 복합 제제 조성물일 경우, 상기 조성물은 제1 성분과 제2 성분이 하나의 제형으로 제제화되어 한번에 투여되는 형태이거나, 제1 성분과 제2 성분이 각각 제제화되어 동시에 또는 시간적 간격을 두고 투여되는 형태를 모두 포함한다. When 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.
이때, 제1 성분과 제2 성분의 사용비율은 중량비 기준으로 1: 0.1 내지 5, 바람직하게는 1:0.5 내지 2로 하는 것이 바람직하다.At this time, 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.
본 발명에 따른 조성물의 투여량은 환자의 상태, 연령, 체중, 질환 정도, 투여 경로 등에 따라서 적절히 조절할 수 있으며, 의사 또는 약사의 판단에 따라 일정 시간 간격으로 1일 1회 또는 일정 시간 간격으로 1일 수회에 걸쳐 분할 투여할 수도 있다. 예컨대, 상기 투여량은 유효성분 함량 기준으로, 0.0001 mg/kg/day 내지 1000 mg/kg/day, 바람직하게는 0.01 mg/kg 내지 500 mg/kg, 더욱 바람직하게는 0.01 mg/kg 내지 100 mg/kg일 수 있으나, 이에 제한되는 것은 아니다. 상기한 투여량은 평균적인 경우를 예시한 것으로서 개인적인 차이에 따라 그 투여량이 높거나 낮을 수 있다. 본 발명의 조성물의 1일 투여량이 상기 투여 용량 미만이면 유의성 있는 효과를 얻을 수 없으며, 그 이상을 초과하는 경우 비경제적일 뿐만 아니라 상용량의 범위를 벗어나므로 바람직하지 않은 부작용이 나타날 우려가 발생할 수 있으므로, 상기 범위로 하는 것이 좋다. 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. For example, 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. If 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.
본 발명에 따른 조성물은 인간을 포함하는 포유동물에 다양한 경로로 투여될 수 있다. 투여 방식은 통상적으로 사용되는 모든 방식일 수 있으며, 예컨대, 경구, 직장 또는 정맥, 근육, 또는 피하 주사에 의해 투여될 수 있다. 본 발명의 조성물은 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 또는 경피제, 좌제 및 멸균 주사용액의 형태의 비경구 제형 등으로 제형화하여 사용될 수 있다. The 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.
본 발명의 조성물은 상기 유효성분 이외에 약제학적으로 적합하고 생리학적으로 허용되는 담체, 부형제 및 희석제 등의 보조제를 추가로 함유하는 것일 수 있다. 본 발명의 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용할 수 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제될 수 있다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제, 경피제 등이 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜 (propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. The 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. When formulated, 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. In addition to simple excipients, 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. As 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.
본 발명의 조성물을 인간에게 적용하는 구체예에 있어서, 본 발명의 조성물은 단독으로 투여될 수 있으나, 일반적으로 투여방식과 표준 약제학적 관행(standard phamaceutical practice)을 고려하여 선택된 약제학적 담체와 혼합되어 투여될 수 있다. 예를 들면, 본 발명의 조성물은 전분 또는 락토오즈를 함유하는 정제 형태로, 또는 단독 또는 부형제를 함유하는 캡슐 형태로, 또는 맛을 내거나 색을 띄게 하는 화학 약품을 함유하는 엘릭시르 또는 현탁제 형태로 경구, 구강내 또는 혀밑 투여될 수 있다. 이러한 액체 제제는 현탁제(예를 들면, 메틸셀룰로오즈, 위텝솔(witepsol)과 같은 반합성 글리세라이드 또는 행인유(apricot kernel oil)와 PEG-6 에스테르의 혼합물 또는 PEG-8과 카프릴릭/카프릭 글리세라이드의 혼합물과 같은 글리세라이드 혼합물)와 같은 약제학적으로 허용 가능한 첨가제와 함께 제형화될 수 있다.In an embodiment in which the composition of the present invention is applied to a human, 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. For example, 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).
이하, 본 발명을 하기의 실시예에 의하여 더욱 상세히 설명한다. 그러나 이들 실시예는 본 발명을 예시하기 위한 것일 뿐이며, 본 발명의 범위가 이들 실시예에 의하여 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to the following examples. However, these examples are only for illustrating the present invention, and the scope of the present invention is not limited by these examples.
<실시예 1> 인진쑥 배지에서 배양한 버섯균사체 추출물 제조 및 유효성분 동정<Example 1> Preparation of mushroom mycelium extract cultured in Injin mugwort medium and identification of active ingredient
건조된 인진쑥 1 kg과 물 2 L를 혼합한 후 110 ℃ 내지 130 ℃에서 약 3시간 동안 멸균시켜서 고체 배지를 얻었다. 다음으로 YMPG(yeast extract malt extract-peptone-glucose) 배지에서 노루궁뎅이 버섯 균사체를 배양시켰다.1 kg of dried phosphorus mugwort and 2 L of water were mixed and sterilized at 110 ° C. to 130 ° C. for about 3 hours to obtain a solid medium. Next, the locust mushroom mycelium was cultured in YMPG (yeast extract malt extract-peptone-glucose) medium.
이후, 상기 인진쑥 고체 배지에 상기 노루궁뎅이 버섯 균사체를 배지 중량의 10중량% 접종한 후 23 ℃ 내지 26 ℃에서 약 45일간 균사를 배양하였다.Subsequently, 10% by weight of the weight of the rotiferous fungus mycelium was inoculated on the jinjin mugwort solid medium, followed by incubation of mycelia at 23 ° C. to 26 ° C. for about 45 days.
상기 배양에 의하여 얻어진 자실체 형성 전 노루궁뎅이 버섯 균사체가 형성된 고체 배지를 건조시켜 인진쑥 배지에서 배양된 노루궁뎅이 버섯 균사체 배양물(Hericium erinaceum Hypha cultivated with Artemisia capillaries, 이하 HEAC)을 얻었다.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).
상기 얻어진 HEAC 건조물 40 g에 메틸렌클로라이드 400 mL를 가하여 40 ℃에서 12시간 동안 추출하고 여과 및 농축하여 3.4g의 추출물을 얻었다(수율: 8.6 %). 400 mL of methylene chloride was added to 40 g of the HEAC dried product, followed by extraction at 40 ° C. for 12 hours, followed by filtration and concentration to obtain 3.4 g of an extract (yield: 8.6%).
상기 얻어진 HEAC의 메틸렌클로라이드 추출물에 대하여 기체 크로마토그래피(GC)를 수행하여 도 1과 같은 결과를 얻었다.Gas chromatography (GC) was performed on the obtained methylene chloride extract of HEAC to obtain a result as shown in FIG. 1.
상기 GC 분석 조건은 다음과 같다:The GC analysis conditions are as follows:
* Column: HP-10, Column: HP-10,
* Carrier gas: 헬륨, Carrier gas: helium,
* Flow rate: 1.5ml/min* Flow rate: 1.5ml / min
* Injection volume: 1.0 ㎕, * Injection volume: 1.0 μl,
* Injector temp.: 280℃* Injector temp .: 280 ℃
* Oven temp.: start at 120℃, stand for 5.0min, increase 10℃/min,Oven temp .: start at 120 ℃, stand for 5.0min, increase 10 ℃ / min,
stand for 5.0min              stand for 5.0min
* Termanal auxl temp.: 300℃, Detector voltage: 1.3kV* Termanal auxl temp .: 300 ℃, Detector voltage: 1.3kV
상기 얻어진 도 1의 각 피크에 대하여 MS(mass spectrometery) 스펙트럼을 분석하였다. 이때 MS 분석 조건은 다음과 같다:MS (mass spectrometery) spectrum was analyzed for each of the peaks of FIG. MS analysis conditions are as follows:
* Column: HP-10, Column: HP-10,
* Carrier gas: 헬륨, Carrier gas: helium,
* Flow rate: 1.5ml/min* Flow rate: 1.5ml / min
* Injection volume: 1.0 ㎕, * Injection volume: 1.0 μl,
* Injector temp.: 280℃* Injector temp .: 280 ℃
* Oven temp.: start at 120℃, stand for 5.0min, increase 10℃/min,Oven temp .: start at 120 ℃, stand for 5.0min, increase 10 ℃ / min,
stand for 5.0min              stand for 5.0min
* Termanal auxl temp.: 300℃, * Termanal auxl temp .: 300 ℃,
* Detector voltage: 1.3kV* Detector voltage: 1.3kV
* Library: NIST. shimadzu Co.Library: NIST. shimadzu Co.
분석 결과, 각 피크 성분은 다음과 같이 밝혀졌다.As a result of analysis, each peak component was found as follows.
① 팔미트산 에틸 에스테르(Palmitic acid ethyl ester)Palmitic acid ethyl ester
② 1-옥탄올(1-Octanol)② 1-octanol
③ 올레산 에틸 에스테르(Oleic acid ethyl ester)③ Oleic acid ethyl ester
④ 스테아르산 에틸 에스테르(Stearic acid ethyl ester)④ Stearic acid ethyl ester
⑤ 파이톨(Phytol)⑤ Phytol
⑥ 리놀레산 에틸 에스테르(Linoleic acid ethyl ester)⑥ Linoleic acid ethyl ester
⑦ 리놀렌산 에틸 에스테르(Linolenic acid ethyl ester)⑦ Linolenic acid ethyl ester
⑧ 에이코사펜타논산 에틸 에스테르(Ethyl eicosapentanoate)⑧ Ethyl eicosapentanoate
⑨ 에이코사놀(Eicosanol)⑨ Eicosanol
이로부터 HEAC의 주요 성분 중에 팔미트산 에틸 에스테르, 올레산 에틸 에스테르, 스테아르산 에틸 에스테르, 리놀레산 에틸 에스테르 및 리놀렌산 에틸 에스테르와 같은 지방산 계열 화합물이 함유되어 있음을 확인하였다.This confirmed that the main components of 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.
<실시예 2> HEAC의 활성성분의 위 보호 효과<Example 2> gastric protective effect of the active ingredient of HEAC
상기 실시예 1에서 분석된 주요 성분의 위 보호 효과를 알아보기 위하여 다음과 같은 시험을 수행하였다.In order to determine the gastric protective effect of the main components analyzed in Example 1, the following test was performed.
구체적으로 7주령된 흰쥐(Sprague-Dawley) 수컷(210±10 g) 8마리씩 그룹화하여 24시간 절식시킨 다음 상기 실시예 1에서 분리한 지방산 계열 화합물들을 증류수 5 mL에 현탁하여 40 mg/kg의 용량으로 경구투여 하였다. 비교군으로는 종래 위염-위궤양 치료제로 사용되는 스틸렌 정(동아제약) 및 셀벡스 캡슐(한일약품)을 사용하였다. 상기 화합물 투여 1시간 후, 위병변 발생 시약으로서 150 mM HCl-EtOH(60%)용액 1.5 mL를 경구 투여하였다. 3시간 경과 후, 피험쥐를 희생시킨 후, 위를 적출하고, 4% 포르말린 10 mL를 위내 주입한 다음 이 용액에서 1시간 고정시켰다. 고정시킨 위를 흐르는 물에 대만부를 따라 절개하고 세척하여 궤양 정도를 측정하였다.Specifically, 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. As a comparison group, styrene tablets (Dong-A Pharm. Co., Ltd.) and Selbex capsules (Hanil Pharm. Co., Ltd.), which are conventionally used for treating gastritis-gastric ulcer, were used. One hour after administration of the compound, 1.5 mL of 150 mM HCl-EtOH (60%) solution was orally administered as a gastric lesion development reagent. After 3 hours, the rats were sacrificed, the stomach was removed, and 10 mL of 4% formalin was injected intragastrically and fixed in this solution for 1 hour. The incidence of ulcers was measured by incision and washing along the Taiwan section in the fixed flowing flowing water.
위병변 억제율은 이 분야에서 일반적으로 채택하고 있는 하기 수학식 1에 의해 계산하였으며, 대조군과의 유의성 검정은 Student's t-test, One-way Analysis of Variance(ANOVA)와 Dunnett' test를 사용하였다.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.
[수학식 1][Equation 1]
Figure PCTKR2010002105-appb-I000001
Figure PCTKR2010002105-appb-I000001
상기 얻어진 HEAC 주요 성분들의 위염-위궤양 억제 효과를 하기 표 1에 나타내었다(피험체 수: 각 시료당 8마리). The gastritis-gastric ulcer inhibitory effect of the HEAC main components obtained is shown in Table 1 (number of subjects: 8 for each sample).
표 1
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%)
대조군 - 50.3±2.5 -
스테아르산 에틸 에스테르 40 24.0±7.1 52.3
팔미트산 에틸 에스테르 40 26.5±11.3 47.3
올레산 에틸 에스테르 40 17.3±3.4 65.7
리놀레산 에틸 에스테르 40 10.8±3.2 78.5
리놀렌산 에틸 에스테르 40 20.8±3.8 58.6
에이코사펜타논산 에틸 에스테르 40 19.3±6.7 61.7
스틸렌 정1) 40 23.0±5.4 54.2
셀벡스 캡슐2) 40 23.5±4.1 53.2
1)스틸렌 정: 동아제약 위염-위궤양 치료제(60 mg as Artemisiae argry Folium 95% EtOH ext.)2)셀벡스 캡슐: 한일약품 위염-위궤양 치료제(50 mg as Teprenone)
Table 1
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition
Control - 50.3 ± 2.5 -
Stearic acid ethyl ester 40 24.0 ± 7.1 52.3
Palmitic Acid Ethyl Ester 40 26.5 ± 11.3 47.3
Oleic acid ethyl ester 40 17.3 ± 3.4 65.7
Linoleic acid ethyl ester 40 10.8 ± 3.2 78.5
Linolenic acid ethyl ester 40 20.8 ± 3.8 58.6
Eicosapentanoic acid ethyl ester 40 19.3 ± 6.7 61.7
Styrene still life 1) 40 23.0 ± 5.4 54.2
Selves capsule 2) 40 23.5 ± 4.1 53.2
1) Styrene information: Company gastric-ulcer agents (60 mg as Artemisiae argry Folium 95 % EtOH ext) 2) cell IBEX capsule: Hanil Pharmaceutical gastric-ulcer agents (50 mg as Teprenone)
표 1에 나타낸 바와 같이, 상기 HEAC에 함유된 지방산 에스테르 화합물은 위염-위궤양 억제율이 47.3~78.5%를 나타냄으로써 종래 위염-위궤양 치료제의 억제율(53.2~54.2%)과 비교하여 볼 때 동등 이상의 위염-위궤양 억제 효과를 나타냄을 알 수 있다. 특히, 리놀레산 에틸 에스테르의 경우에는 단독 사용시에도 위염-위궤양 억제율이 78.5%를 나타냄으로써 위염-위궤양 억제 효과가 탁월함을 확인하였다.As shown in Table 1, 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.
따라서 본 발명에 따른 지방산 에스테르 화합물은 위벽을 보호하여 위염-위궤양의 병변을 억제하는 효과가 뛰어나므로 위벽 보호 및 위장 질환 치료제로서 유용하게 사용될 수 있다.Therefore, 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.
<실시예 3> 지방산 계열 화합물의 위 보호 효과Example 3 Gastric Protective Effects of Fatty Acid-Based Compounds
본 발명에 따른 지방산 또는 이들의 에틸 에스테르 화합물의 위 보호 효과를 알아보기 위하여 상기 실시예 2와 동일한 방법으로 위병변 억제 효과를 시험하여 그 결과를 표 2 및 표 3에 나타내었다.In order to determine the gastric protective effect of the fatty acids or ethyl ester compounds thereof according to the present invention, the effect of inhibiting gastric lesions was tested in the same manner as in Example 2, and the results are shown in Table 2 and Table 3.
표 2 지방산 화합물의 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%)
대조군 - 32.4±3.68 -
포화지방산계열 부티르산 40 30.0±5.28 7.5
카프로산 40 29.6±5.65 8.6
카프릴산 40 28.1±4.90 13.4
카프르산 40 26.8±5.02 17.4
라우르산 40 26.4±5.59 18.7
미리스트산 40 25.7±5.97 20.8
2,4,6,8-테트라메틸데카논산 40 20.1±4.18 37.9
팔미트산 40 17.2±2.53 47.1
스테아르산 40 15.9±2.97 51.0
디하이드로스테르쿨린산 40 22.8±2.34 29.7
튜베르큘로스테아르산 40 17.7±2.36 45.4
아라키드산 40 14.0±3.86 56.9
베헨산 40 14.6±2.90 55.1
리그노세르산 40 14.1±3.99 56.4
세로트산 40 13.9±2.28 57.1
몬타닌산 40 12.7±2.14 61.0
멜리스산 40 14.0±2.89 56.9
코리노미콜산 40 18.9±4.65 41.8
불포화지방산계열 디하이드로메트리카리아산 40 20.4±3.52 37.0
운데세노산 40 18.7±3.80 42.4
히드노카르프산 40 23.9±4.74 26.2
팔미톨레산 40 15.3±2.78 52.9
차울무그르산 40 20.0±3.89 38.3
말발산 40 19.8±3.20 39.0
올레산 40 11.5±2.60 64.4
리시놀레산 40 15.1±3.19 53.3
시스-박센산 40 16.4±3.05 49.5
리놀레산 40 9.3±2.14 71.3
크레페닌산 40 14.0±2.88 56.7
디하이드로크레페닌산 40 13.2±2.67 59.4
α-리놀렌산 40 13.6±2.28 58.2
γ-리놀렌산 40 16.5±3.02 49.2
스테아리돈산 40 14.8±3.01 54.3
스테르쿨린산 40 22.7±4.21 29.9
가돌레산 40 19.7±3.11 39.1
DHLA(Dihomo-γ-Linolenic acid) 40 14.1±1.87 56.5
에이코사테트라에노산 40 15.3±3.48 52.9
아라키돈산 40 12.6±2.54 61.3
에이코사펜타에노산(EPA) 40 12.8±2.02 60.5
에루스산 40 18.6±4.49 42.7
치코르산 40 14.5±3.35 55.2
도코사펜타에노산(DPA) 40 13.4±2.41 58.7
도코사헥사에노산(DHA) 40 12.8±3.37 60.4
네르본산 40 17.3±2.21 46.7
평균값은 P<0.05와 크게 다르지 않다(Student t-test)
TABLE 2 <u> Gastroenteritis-Gastrointestinal Inhibitory Effect of Fatty Acid Compounds </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition
Control - 32.4 ± 3.68 -
Saturated Fatty Acid Butyric acid 40 30.0 ± 5.28 7.5
Caproic acid 40 29.6 ± 5.65 8.6
Caprylic acid 40 28.1 ± 4.90 13.4
Capric acid 40 26.8 ± 5.02 17.4
Lauric acid 40 26.4 ± 5.59 18.7
Myristic acid 40 25.7 ± 5.97 20.8
2,4,6,8-tetramethyldecanoic acid 40 20.1 ± 4.18 37.9
Palmitic acid 40 17.2 ± 2.53 47.1
Stearic acid 40 15.9 ± 2.97 51.0
Dihydrosterulic acid 40 22.8 ± 2.34 29.7
Tuberculostearic acid 40 17.7 ± 2.36 45.4
Arachidic acid 40 14.0 ± 3.86 56.9
Behenic acid 40 14.6 ± 2.90 55.1
Lignoseric acid 40 14.1 ± 3.99 56.4
Sertosan 40 13.9 ± 2.28 57.1
Montanic acid 40 12.7 ± 2.14 61.0
Melis acid 40 14.0 ± 2.89 56.9
Corinomic Acid 40 18.9 ± 4.65 41.8
Unsaturated fatty acid Dihydrometric acid 40 20.4 ± 3.52 37.0
Undeseno 40 18.7 ± 3.80 42.4
Hydrnocarpic acid 40 23.9 ± 4.74 26.2
Palmitoleic acid 40 15.3 ± 2.78 52.9
Chammurgresan 40 20.0 ± 3.89 38.3
Malvale 40 19.8 ± 3.20 39.0
Oleic acid 40 11.5 ± 2.60 64.4
Ricinoleic acid 40 15.1 ± 3.19 53.3
Cis-bacsen 40 16.4 ± 3.05 49.5
Linoleic acid 40 9.3 ± 2.14 71.3
Crephenic acid 40 14.0 ± 2.88 56.7
Dihydrocrephenic acid 40 13.2 ± 2.67 59.4
α-linolenic acid 40 13.6 ± 2.28 58.2
γ-linolenic acid 40 16.5 ± 3.02 49.2
Stearic acid 40 14.8 ± 3.01 54.3
Sterulic acid 40 22.7 ± 4.21 29.9
Gadoleic acid 40 19.7 ± 3.11 39.1
Dihomo-γ-Linolenic acid (DHLA) 40 14.1 ± 1.87 56.5
Eicosatetraenoic acid 40 15.3 ± 3.48 52.9
Arachidonic acid 40 12.6 ± 2.54 61.3
Eicosapentaenoic acid (EPA) 40 12.8 ± 2.02 60.5
Mount Erus 40 18.6 ± 4.49 42.7
Chicorsan 40 14.5 ± 3.35 55.2
Docosapentaenoic Acid (DPA) 40 13.4 ± 2.41 58.7
Docosahexaenoic Acid (DHA) 40 12.8 ± 3.37 60.4
Nerbonic acid 40 17.3 ± 2.21 46.7
The mean value is not significantly different from P <0.05 (Student t-test)
표 3 지방산 에스테르 화합물의 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%)
대조군 - 29.8±4.75 -
포화지방산계열 부티르산 에틸 에스테르 40 27.1±5.51 9.1
카프로산 에틸 에스테르 40 26.9±6.32 9.7
카프릴산 에틸 에스테르 40 24.9±6.43 16.4
카프르산 에틸 에스테르 40 23.4±5.74 21.6
라우르산 에틸 에스테르 40 23.6±6.06 20.7
미리스트산 에틸 에스테르 40 23.1±6.04 22.4
2,4,6,8-테트라메틸데카논산 에틸 에스테르 40 18.0±3.75 39.6
팔미트산 에틸 에스테르 40 15.3±2.59 48.8
스테아르산 에틸 에스테르 40 13.7±2.98 54.2
디하이드로스테르쿨린산 에틸 에스테르 40 20.8±3.27 30.1
튜베르큘로스테아르산 에틸 에스테르 40 15.7±1.92 47.5
아라키드산 에틸 에스테르 40 12.5±3.28 58.0
베헨산 에틸 에스테르 40 12.4±3.09 58.4
리그노세르산 에틸 에스테르 40 12.4±3.08 58.6
세로트산 에틸 에스테르 40 12.0±2.16 59.8
몬타닌산 에틸 에스테르 40 11.3±2.26 62.2
멜리스산 에틸 에스테르 40 11.4±2.69 61.7
코리노미콜산 에틸 에스테르 40 15.9±3.73 46.6
불포화지방산계열 데카-2-엔-4,6,8-트리이노산 에틸 에스테르 40 18.5±4.28 37.9
운데세노산 에틸 에스테르 40 16.6±3.97 44.3
히드노카르프산 에틸 에스테르 40 20.7±3.85 30.5
팔미톨레산 에틸 에스테르 40 12.6±2.89 57.8
차울무그르산 에틸 에스테르 40 16.7±4.64 44.0
말발산 에틸 에스테르 40 16.4±2.84 45.0
올레산 에틸 에스테르 40 10.2±2.75 65.9
리시놀레산 에틸 에스테르 40 12.2±2.56 59.1
박센산 에틸 에스테르 40 13.7±1.98 54.2
리놀레산 에틸 에스테르 40 8.3±1.32 78.5
크레페닌산 에틸 에스테르 40 10.8±2.31 63.8
디하이드로크레페닌산 에틸 에스테르 40 9.9±1.97 66.7
리놀렌산 에틸 에스테르 40 11.8±2.42 60.3
α-리놀렌산 에틸 에스테르 40 13.7±3.07 53.9
γ-리놀렌산 에틸 에스테르 40 11.5±2.02 61.4
스테아리돈산 에틸 에스테르 40 12.4±3.29 58.3
스테르쿨린산 에틸 에스테르 40 19.2±4.65 35.7
가돌레산 에틸 에스테르 40 16.0±2.79 46.5
에이코사테트라에노산 에틸 에스테르 40 11.6±2.93 61.1
아라키돈산 에틸 에스테르 40 11.0±2.73 63.3
에이코사펜타에노산 에틸 에스테르 40 11.1±2.48 62.8
에루스산 에틸 에스테르 40 15.8±4.06 47.0
치코르산 에틸 에스테르 40 11.1±3.06 62.8
도코사펜타에노산 에틸 에스테르 40 10.9±2.48 63.5
도코사헥사에노산 에틸 에스테르 40 10.7±2.74 64.0
네르본산 에틸 에스테르 40 15.3±2.29 48.7
평균값은 P<0.05와 크게 다르지 않다(Student t-test)
TABLE 3 <u> Gastroenteritis-Gastrointestinal Inhibitory Effect of Fatty Acid Ester Compounds </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition
Control - 29.8 ± 4.75 -
Saturated Fatty Acid Butyric acid ethyl ester 40 27.1 ± 5.51 9.1
Caproic acid ethyl ester 40 26.9 ± 6.32 9.7
Caprylic Acid Ethyl Ester 40 24.9 ± 6.43 16.4
Capric acid ethyl ester 40 23.4 ± 5.74 21.6
Lauric acid ethyl ester 40 23.6 ± 6.06 20.7
Myristic acid ethyl ester 40 23.1 ± 6.04 22.4
2,4,6,8-tetramethyldecanoic acid ethyl ester 40 18.0 ± 3.75 39.6
Palmitic Acid Ethyl Ester 40 15.3 ± 2.59 48.8
Stearic acid ethyl ester 40 13.7 ± 2.98 54.2
Dihydrosterulic acid ethyl ester 40 20.8 ± 3.27 30.1
Tuberculostearic acid ethyl ester 40 15.7 ± 1.92 47.5
Arachidic Ethyl Ester 40 12.5 ± 3.28 58.0
Behenic acid ethyl ester 40 12.4 ± 3.09 58.4
Lignoseric acid ethyl ester 40 12.4 ± 3.08 58.6
Sertoic acid ethyl ester 40 12.0 ± 2.16 59.8
Montanic Acid Ethyl Ester 40 11.3 ± 2.26 62.2
Melisic acid ethyl ester 40 11.4 ± 2.69 61.7
Corinomycolic Acid Ethyl Ester 40 15.9 ± 3.73 46.6
Unsaturated fatty acid Deca-2-ene-4,6,8-triinoic acid ethyl ester 40 18.5 ± 4.28 37.9
Undecenoic acid ethyl ester 40 16.6 ± 3.97 44.3
Hydnocarboxylic Acid Ethyl Ester 40 20.7 ± 3.85 30.5
Palmitoleic Acid Ethyl Ester 40 12.6 ± 2.89 57.8
Chammuric acid ethyl ester 40 16.7 ± 4.64 44.0
Malvalic acid ethyl ester 40 16.4 ± 2.84 45.0
Oleic acid ethyl ester 40 10.2 ± 2.75 65.9
Ricinoleic acid ethyl ester 40 12.2 ± 2.56 59.1
Bacsenic acid ethyl ester 40 13.7 ± 1.98 54.2
Linoleic acid ethyl ester 40 8.3 ± 1.32 78.5
Crephenic Acid Ethyl Ester 40 10.8 ± 2.31 63.8
Dihydrocrephenic acid ethyl ester 40 9.9 ± 1.97 66.7
Linolenic acid ethyl ester 40 11.8 ± 2.42 60.3
α-linolenic acid ethyl ester 40 13.7 ± 3.07 53.9
γ-linolenic acid ethyl ester 40 11.5 ± 2.02 61.4
Stearic Acid Ethyl Ester 40 12.4 ± 3.29 58.3
Sterkulic acid ethyl ester 40 19.2 ± 4.65 35.7
Gadoleic Acid Ethyl Ester 40 16.0 ± 2.79 46.5
Eicosatetraenoic acid ethyl ester 40 11.6 ± 2.93 61.1
Arachidonic acid ethyl ester 40 11.0 ± 2.73 63.3
Eicosapentaenoic acid ethyl ester 40 11.1 ± 2.48 62.8
Erucic acid ethyl ester 40 15.8 ± 4.06 47.0
Chicoric Acid Ethyl Ester 40 11.1 ± 3.06 62.8
Docosapentaenoic Acid Ethyl Ester 40 10.9 ± 2.48 63.5
Docosahexaenoic Acid Ethyl Ester 40 10.7 ± 2.74 64.0
Nerbornic acid ethyl ester 40 15.3 ± 2.29 48.7
The mean value is not significantly different from P <0.05 (Student t-test)
표 2 및 표 3에 나타낸 바와 같이, 스테아르산, 아라키드산, 베헨산, 리그노세르산, 세로트산, 몬타닌산, 멜리스산, 팔미톨레산, 올레산, 리시놀레산, 리놀레산, 크레페닌산, 디하이드로크레페닌산, 리놀렌산, 스테아리돈산, DHLA, 에이코사테트라에노산, 아라키돈산, 에이코사펜타에노산, 치코르산, 도코사펜타에노산, 도코사헥사에노산 등의 지방산 화합물 또는 이의 에틸 에스테르 화합물에서 50% 이상의 위염-위궤양 억제율이 나타났다. 특히, 리놀레산의 경우에는 지방산일 때 71.3%, 에스테르 화합물일 때 78.5%의 위염-위궤양 억제율이 나타났다.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. In particular, linoleic acid showed a gastritis-gastric ulcer inhibition rate of 71.3% for fatty acids and 78.5% for ester compounds.
따라서, 본 발명에 따른 지방산 또는 이의 에스테르 화합물은 위벽을 보호하여 위염-위궤양의 병변을 억제하는 효과가 뛰어나므로 위벽 보호 및 위장 질환 치료제로서 유용하게 사용될 수 있다.Therefore, 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.
<실시예 4> 지방산 계열 화합물과 유효약물과의 병용 투여시 위 보호 효과Example 4 Stomach Protective Effect in Combination Administration of Fatty Acid-Based Compounds and Effective Drugs
본 발명에 따른 지방산 계열 화합물을 통상적으로 사용되는 위염, 위궤양의 위병변 치료제와 병용 투여하는 경우의 우수한 상승 효과를 확인하기 위하여 다음과 같은 실험을 수행하였다.In order to confirm the excellent synergistic effect of the fatty acid-based compound according to the present invention in combination with a commonly used gastritis treatment agent for gastritis and gastric ulcer, the following experiment was performed.
(1) 지방산 계열 화합물과 H(1) fatty acid compounds and H 22 수용체 길항제의 병용 투여 Concomitant Administration of Receptor Antagonists
상기 실시예 3에서 시험된 지방산 계열 화합물과 H2 수용체 길항제로서 라니티딘(경보제약), 시메티딘(명문제약), 파모티딘(한미약품), 록사티딘(롯데제약), 니자티딘(한국넬슨제약)을 중량 기준으로 1:1 병용 투여하는 것을 제외하고는 상기 실시예 2와 동일한 방법으로 위병변 억제 효과를 측정하였다.As the fatty acid-based compound and H 2 receptor antagonist tested in Example 3, ranitidine (alarm drug), cimetidine (light drug), pamotidine (Hanmi 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.
측정 결과를 표 4 및 표 5에 나타내었다.The measurement results are shown in Tables 4 and 5.
표 4 라니티딘과 지방산 에스테르 화합물의 병용 투여에 따른 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%)
대조군 - 40.7±4.80 -
라니티딘1) 40 17.6±3.61 56.9
라니티딘+포화지방산계열 부티르산 에틸 에스테르 20/20 28.6±2.67 29.7
카프로산 에틸 에스테르 20/20 28.0±3.16 31.2
카프릴산 에틸 에스테르 20/20 27.3±4.24 32.9
카프르산 에틸 에스테르 20/20 25.9±3.29 36.4
라우르산 에틸 에스테르 20/20 24.7±5.74 39.3
미리스트산 에틸 에스테르 20/20 22.6±3.12 44.5
2,4,6,8-테트라메틸데카논산 에틸 에스테르 20/20 16.0±2.08 60.7
팔미트산 에틸 에스테르 20/20 14.8±2.34 63.6
스테아르산 에틸 에스테르 20/20 13.7±3.16 66.3
디하이드로스테르쿨린산 에틸 에스테르 20/20 20.3±1.28 50.1
튜베르큘로스테아르산 에틸 에스테르 20/20 15.0±2.82 53.1
아라키드산 에틸 에스테르 20/20 10.8±1.97 73.5
베헨산 에틸 에스테르 20/20 10.6±2.61 74.0
리그노세르산 에틸 에스테르 20/20 10.5±1.84 74.2
세로트산 에틸 에스테르 20/20 10.1±3.72 75.2
몬타닌산 에틸 에스테르 20/20 9.5±1.28 76.7
멜리스산 에틸 에스테르 20/20 9.7±1.33 76.2
코리노미콜산 에틸 에스테르 20/20 15.4±2.40 62.2
라니티딘+불포화지방산계열 (E)-데카-2-엔-4,6,8-트리이노산 에틸 에스테르 20/20 17.2±1.36 57.7
운데세노산 에틸 에스테르 20/20 16.0±3.46 60.7
히드노카르프산 에틸 에스테르 20/20 19.8±2.64 51.4
팔미톨레산 에틸 에스테르 20/20 11.0±1.38 73.0
차울무그르산 에틸 에스테르 20/20 16.3±3.44 60.0
말발산 에틸 에스테르 20/20 15.9±4.68 60.9
올레산 에틸 에스테르 20/20 8.3±1.20 79.6
리시놀레산 에틸 에스테르 20/20 10.4±2.54 74.4
박센산 에틸 에스테르 20/20 12.0±3.66 70.5
리놀레산 에틸 에스테르 20/20 5.0±0.72 87.7
크레페닌산 에틸 에스테르 20/20 8.8±1.31 78.4
디하이드로크레페닌산 에틸 에스테르 20/20 5.5±0.82 86.5
리놀렌산 에틸 에스테르 20/20 9.6±1.65 76.4
α-리놀렌산 에틸 에스테르 20/20 12.1±3.47 70.3
γ-리놀렌산 에틸 에스테르 20/20 9.4±1.55 76.9
스테아리돈산 에틸 에스테르 20/20 10.2±1.61 74.9
스테르쿨린산 에틸 에스테르 20/20 17.6±1.35 56.8
가돌레산 에틸 에스테르 20/20 45.6±3.64 61.7
에이코사테트라에노산 에틸 에스테르 20/20 9.5±2.01 76.7
아라키돈산 에틸 에스테르 20/20 9.0±2.30 77.9
에이코사펜타에노산 에틸 에스테르 20/20 9.3±1.43 77.1
에루스산 에틸 에스테르 20/20 16.1±3.84 60.4
치코르산 에틸 에스테르 20/20 9.4±2.81 76.9
도코사펜타에노산 에틸 에스테르 20/20 8.7±1.32 78.6
도코사헥사에노산 에틸 에스테르 20/20 8.1±2.09 80.1
네르본산 에틸 에스테르 20/20 13.2±4.62 67.6
평균값은 P<0.05와 크게 다르지 않다(Student t-test) 1)라니티딘정: 경보제약 위/십이지장 궤양 치료제(75 mg as Ranitidine)
Table 4 <u> Gastroenteritis-Gastrointestinal Inhibitory Effect of Co-administration of Ranitidine and Fatty Acid Ester Compounds </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition
Control - 40.7 ± 4.80 -
Ranitidine 1) 40 17.6 ± 3.61 56.9
Ranitidine + Saturated Fatty Acid Butyric acid ethyl ester 20/20 28.6 ± 2.67 29.7
Caproic acid ethyl ester 20/20 28.0 ± 3.16 31.2
Caprylic Acid Ethyl Ester 20/20 27.3 ± 4.24 32.9
Capric acid ethyl ester 20/20 25.9 ± 3.29 36.4
Lauric acid ethyl ester 20/20 24.7 ± 5.74 39.3
Myristic acid ethyl ester 20/20 22.6 ± 3.12 44.5
2,4,6,8-tetramethyldecanoic acid ethyl ester 20/20 16.0 ± 2.08 60.7
Palmitic Acid Ethyl Ester 20/20 14.8 ± 2.34 63.6
Stearic acid ethyl ester 20/20 13.7 ± 3.16 66.3
Dihydrosterulic acid ethyl ester 20/20 20.3 ± 1.28 50.1
Tuberculostearic acid ethyl ester 20/20 15.0 ± 2.82 53.1
Arachidic Ethyl Ester 20/20 10.8 ± 1.97 73.5
Behenic acid ethyl ester 20/20 10.6 ± 2.61 74.0
Lignoseric acid ethyl ester 20/20 10.5 ± 1.84 74.2
Sertoic acid ethyl ester 20/20 10.1 ± 3.72 75.2
Montanic Acid Ethyl Ester 20/20 9.5 ± 1.28 76.7
Melisic acid ethyl ester 20/20 9.7 ± 1.33 76.2
Corinomycolic Acid Ethyl Ester 20/20 15.4 ± 2.40 62.2
Ranitidine + unsaturated fatty acid series (E) -deca-2-ene-4,6,8-triinoic acid ethyl ester 20/20 17.2 ± 1.36 57.7
Undecenoic acid ethyl ester 20/20 16.0 ± 3.46 60.7
Hydnocarboxylic Acid Ethyl Ester 20/20 19.8 ± 2.64 51.4
Palmitoleic Acid Ethyl Ester 20/20 11.0 ± 1.38 73.0
Chammuric acid ethyl ester 20/20 16.3 ± 3.44 60.0
Malvalic acid ethyl ester 20/20 15.9 ± 4.68 60.9
Oleic acid ethyl ester 20/20 8.3 ± 1.20 79.6
Ricinoleic acid ethyl ester 20/20 10.4 ± 2.54 74.4
Bacsenic acid ethyl ester 20/20 12.0 ± 3.66 70.5
Linoleic acid ethyl ester 20/20 5.0 ± 0.72 87.7
Crephenic Acid Ethyl Ester 20/20 8.8 ± 1.31 78.4
Dihydrocrephenic acid ethyl ester 20/20 5.5 ± 0.82 86.5
Linolenic acid ethyl ester 20/20 9.6 ± 1.65 76.4
α-linolenic acid ethyl ester 20/20 12.1 ± 3.47 70.3
γ-linolenic acid ethyl ester 20/20 9.4 ± 1.55 76.9
Stearic Acid Ethyl Ester 20/20 10.2 ± 1.61 74.9
Sterkulic acid ethyl ester 20/20 17.6 ± 1.35 56.8
Gadoleic Acid Ethyl Ester 20/20 45.6 ± 3.64 61.7
Eicosatetraenoic acid ethyl ester 20/20 9.5 ± 2.01 76.7
Arachidonic acid ethyl ester 20/20 9.0 ± 2.30 77.9
Eicosapentaenoic acid ethyl ester 20/20 9.3 ± 1.43 77.1
Erucic acid ethyl ester 20/20 16.1 ± 3.84 60.4
Chicoric Acid Ethyl Ester 20/20 9.4 ± 2.81 76.9
Docosapentaenoic Acid Ethyl Ester 20/20 8.7 ± 1.32 78.6
Docosahexaenoic Acid Ethyl Ester 20/20 8.1 ± 2.09 80.1
Nerbornic acid ethyl ester 20/20 13.2 ± 4.62 67.6
The average value P <do not differ greatly from the 0.05 (Student t-test) 1 ) ranitidine tablet: Security restrictions up / duodenal ulcer treatment (75 mg as Ranitidine)
표 5 시메티딘, 파모티딘, 록사티딘 또는 니자티딘과 지방산 에스테르 화합물의 병용 투여에 따른 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%)
대조군 - 41.2±4.23 -
시메티딘1) 단독 40 18.4±4.59 55.3
시메티딘+지방산계열 올레산 에틸 에스테르 20/20 10.2±1.64 75.2
리놀레산 에틸 에스테르 20/20 8.6±2.37 79.1
디하이드로크레페닌산 에틸 에스테르 20/20 9.3±3.06 77.4
도코사헥사에노산 에틸 에스테르 20/20 11.9±2.48 71.1
아라키돈산 에틸 에스테르 20/20 9.0±1.82 78.2
파모티딘2) 단독 40 16.3±3.84 60.4
파모티딘+지방산계열 올레산 에틸 에스테르 20/20 9.7±1.64 76.5
리놀레산 에틸 에스테르 20/20 8.4±2.49 79.6
디하이드로크레페닌산 에틸 에스테르 20/20 8.8±2.40 78.6
도코사헥사에노산 에틸 에스테르 20/20 11.4±1.92 72.3
아라키돈산 에틸 에스테르 20/20 8.7±3.08 78.9
록사티딘3) 단독 40 15.7±3.55 61.9
록사티딘+지방산계열 올레산 에틸 에스테르 20/20 9.0±1.43 78.2
리놀레산 에틸 에스테르 20/20 7.8±1.39 81.1
디하이드로크레페닌산 에틸 에스테르 20/20 8.1±2.04 80.3
도코사헥사에노산 에틸 에스테르 20/20 10.3±3.41 75.0
아라키돈산 에틸 에스테르 20/20 8.0±1.43 80.6
니자티딘4) 단독 40 15.4±4.54 62.6
니자티딘+지방산계열 올레산 에틸 에스테르 20/20 8.2±1.92 80.1
리놀레산 에틸 에스테르 20/20 7.0±1.65 93.0
디하이드로크레페닌산 에틸 에스테르 20/20 7.5±2.58 81.8
도코사헥사에노산 에틸 에스테르 20/20 9.5±3.75 76.9
아라키돈산 에틸 에스테르 20/20 7.3±0.72 82.3
평균값은 P<0.05와 크게 다르지 않다(Student t-test) 1)시메티딘정: 명문제약 위/십이지장 궤양 치료제(200 mg as Cimetidine) 2)파모티딘정: 한미약품 위/십이지장 궤양 치료제(20 mg as Famotidine) 3)록사티딘 캡슐: 롯데제약 위/십이지장 궤양 치료제(75 mg as Loxatidine) 4)니자티딘정: 한국넬슨제약 위산과다 치료제(75 mg as Nizatidine)
Table 5 <u> Efficacy of gastritis-gastric ulcer by the combined administration of cimetidine, pamotidine, roxathidine or nizatidine with fatty acid ester compounds </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition
Control - 41.2 ± 4.23 -
Cimetidine 1) alone 40 18.4 ± 4.59 55.3
Cimetidine + Fatty Acid Oleic acid ethyl ester 20/20 10.2 ± 1.64 75.2
Linoleic acid ethyl ester 20/20 8.6 ± 2.37 79.1
Dihydrocrephenic acid ethyl ester 20/20 9.3 ± 3.06 77.4
Docosahexaenoic Acid Ethyl Ester 20/20 11.9 ± 2.48 71.1
Arachidonic acid ethyl ester 20/20 9.0 ± 1.82 78.2
Famotidine 2) alone 40 16.3 ± 3.84 60.4
Famotidine + Fatty Acid Oleic acid ethyl ester 20/20 9.7 ± 1.64 76.5
Linoleic acid ethyl ester 20/20 8.4 ± 2.49 79.6
Dihydrocrephenic acid ethyl ester 20/20 8.8 ± 2.40 78.6
Docosahexaenoic Acid Ethyl Ester 20/20 11.4 ± 1.92 72.3
Arachidonic acid ethyl ester 20/20 8.7 ± 3.08 78.9
Roxatidine 3) alone 40 15.7 ± 3.55 61.9
Roxatidine + fatty acid series Oleic acid ethyl ester 20/20 9.0 ± 1.43 78.2
Linoleic acid ethyl ester 20/20 7.8 ± 1.39 81.1
Dihydrocrephenic acid ethyl ester 20/20 8.1 ± 2.04 80.3
Docosahexaenoic Acid Ethyl Ester 20/20 10.3 ± 3.41 75.0
Arachidonic acid ethyl ester 20/20 8.0 ± 1.43 80.6
Nizatidine 4) alone 40 15.4 ± 4.54 62.6
Nizatidine + fatty acid series Oleic acid ethyl ester 20/20 8.2 ± 1.92 80.1
Linoleic acid ethyl ester 20/20 7.0 ± 1.65 93.0
Dihydrocrephenic acid ethyl ester 20/20 7.5 ± 2.58 81.8
Docosahexaenoic Acid Ethyl Ester 20/20 9.5 ± 3.75 76.9
Arachidonic acid ethyl ester 20/20 7.3 ± 0.72 82.3
The average value is much different from the P <0.05 (Student t-test ) 1) cimetidine tablets: prestigious pharmaceutical Up / duodenal ulcer therapeutic agent (200 mg as Cimetidine) 2) wave motif dinjeong: Company stomach / duodenal ulcer treatment (20 mg as Famotidine) 3) Roxathidine Capsule: Lotte Pharmaceutical's gastric / duodenal ulcer treatment (75 mg as Loxatidine) 4) Nizatidine tablet: Korea Nelson Pharmaceutical's gastric hyperacid treatment (75 mg as Nizatidine)
표 4 및 표 5에 나타낸 바와 같이, 올레산 에틸 에스테르, 리놀레산 에틸 에스테르, 디하이드로크레페닌산 에틸 에스테르, 도코사헥사에노산 에틸 에스테르, 아라키돈산 에틸 에스테르 등의 본 발명에 따른 지방산의 에스테르 화합물과 H2 수용체 길항제를 병용 투여하는 경우, H2 수용체 길항제 단독 투여시보다 위염-위궤양 억제율이 유의적으로 상승하는 것으로 나타났으며, 특히 리놀레산 에틸 에스테르를 사용한 경우에는 H2 수용체 길항제 단독 투여시보다 위염-위궤양 억제율이 20% 이상 상승하는 것으로 나타났다.As shown in Tables 4 and 5, ester compounds of fatty acids and H 2 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. 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%.
따라서, 본 발명에 따른 지방산 또는 이의 에스테르 화합물은 위벽을 보호하여 위염-위궤양의 병변을 억제하는 효과가 뛰어나므로 위벽 보호 및 위장 질환 치료제로서 유용하게 사용될 수 있다.Therefore, 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.
(2) 지방산 계열 화합물과 프로톤 펌프 저해제의 병용 투여(2) Concomitant Administration of Fatty Acid Compounds and Proton Pump Inhibitors
상기 실시예 3에서 시험된 지방산 계열 화합물과 프로톤 펌프 저해제로서 오메프라졸(종근당), 란소프라졸(안국약품), 판토프라졸(한불제약), 라베프라졸(바이넥스), 레바프라잔(유한양행), 일라프라졸(일양약품), 에스오메프라졸(한미약품)을 중량 기준으로 1:1 병용 투여하는 것을 제외하고는 상기 실시예 2와 동일한 방법으로 위병변 억제 효과를 측정하였다.As the fatty acid-based compound and proton pump inhibitors tested in Example 3, 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.
측정 결과를 표 6 및 표 7에 나타내었다.The measurement results are shown in Table 6 and Table 7.
표 6 오메프라졸과 지방산 에스테르 화합물의 병용 투여에 따른 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%)
대조군 - 33.1±4.29 -
오메프라졸1) 40 12.8±2.69 61.3
오메프라졸+포화지방산계열 부티르산 에틸 에스테르 20/20 21.4±3.64 35.3
카프로산 에틸 에스테르 20/20 21.2±8.62 36.0
카프릴산 에틸 에스테르 20/20 19.2±4.26 42.0
카프르산 에틸 에스테르 20/20 17.7±1.34 46.5
라우르산 에틸 에스테르 20/20 17.9±2.59 45.9
미리스트산 에틸 에스테르 20/20 17.4±4.56 47.4
2,4,6,8-테트라메틸데카논산 에틸 에스테르 20/20 12.3±4.34 62.8
팔미트산 에틸 에스테르 20/20 9.6±3.75 71.0
스테아르산 에틸 에스테르 20/20 8.0±2.08 75.8
디하이드로스테르쿨린산 에틸 에스테르 20/20 15.1±6.01 54.4
튜베르큘로스테아르산 에틸 에스테르 20/20 10.0±3.66 69.8
아라키드산 에틸 에스테르 20/20 6.8±1.74 79.5
베헨산 에틸 에스테르 20/20 6.7±2.28 79.8
리그노세르산 에틸 에스테르 20/20 6.7±1.44 79.8
세로트산 에틸 에스테르 20/20 6.3±2.06 81.0
몬타닌산 에틸 에스테르 20/20 5.6±2.28 83.1
멜리스산 에틸 에스테르 20/20 5.7±1.06 82.8
코리노미콜산 에틸 에스테르 20/20 10.2±3.06 69.2
오메프라졸+불포화지방산계열 (E)-데카-2-엔-4,6,8-트리이노산 에틸 에스테르 20/20 12.8±2.69 61.3
운데세노산 에틸 에스테르 20/20 10.9±1.25 67.1
히드노카르프산 에틸 에스테르 20/20 15.0±2.46 54.7
팔미톨레산 에틸 에스테르 20/20 6.9±2.14 79.2
차울무그르산 에틸 에스테르 20/20 11.0±2.34 66.8
말발산 에틸 에스테르 20/20 10.7±2.37 67.7
올레산 에틸 에스테르 20/20 4.5±1.02 86.4
리시놀레산 에틸 에스테르 20/20 6.5±1.61 80.4
박센산 에틸 에스테르 20/20 8.0±2.33 75.8
리놀레산 에틸 에스테르 20/20 2.6±0.37 92.1
크레페닌산 에틸 에스테르 20/20 5.1±1.00 84.6
디하이드로크레페닌산 에틸 에스테르 20/20 4.2±2.01 87.3
리놀렌산 에틸 에스테르 20/20 6.1±2.67 81.6
α-리놀렌산 에틸 에스테르 20/20 8.0±1.32 75.8
γ-리놀렌산 에틸 에스테르 20/20 5.8±1.24 82.5
스테아리돈산 에틸 에스테르 20/20 6.7±1.19 79.8
스테르쿨린산 에틸 에스테르 20/20 13.5±2.68 59.2
가돌레산 에틸 에스테르 20/20 10.3±3.33 68.9
에이코사테트라에노산 에틸 에스테르 20/20 5.9±2.00 82.2
아라키돈산 에틸 에스테르 20/20 5.3±1.03 84.0
에이코사펜타에노산 에틸 에스테르 20/20 5.4±2.46 83.7
에루스산 에틸 에스테르 20/20 10.1±3.25 69.5
치코르산 에틸 에스테르 20/20 5.4±1.69 83.7
도코사펜타에노산 에틸 에스테르 20/20 5.2±2.08 84.3
도코사헥사에노산 에틸 에스테르 20/20 5.0±1.22 84.9
네르본산 에틸 에스테르 20/20 9.6±2.84 71.0
평균값은 P<0.05와 크게 다르지 않다(Student t-test) 1)오메프라졸정: 종근당 위/십이지장 궤양 치료제(20 mg as Omeprazole)
Table 6 <u> Gastroenteritis-Gastrointestinal Inhibitory Effect by Combination Administration of Omeprazole and Fatty Acid Ester Compounds </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition
Control - 33.1 ± 4.29 -
Omeprazole 1) 40 12.8 ± 2.69 61.3
Omeprazole + Saturated Fatty Acid Butyric acid ethyl ester 20/20 21.4 ± 3.64 35.3
Caproic acid ethyl ester 20/20 21.2 ± 8.62 36.0
Caprylic Acid Ethyl Ester 20/20 19.2 ± 4.26 42.0
Capric acid ethyl ester 20/20 17.7 ± 1.34 46.5
Lauric acid ethyl ester 20/20 17.9 ± 2.59 45.9
Myristic acid ethyl ester 20/20 17.4 ± 4.56 47.4
2,4,6,8-tetramethyldecanoic acid ethyl ester 20/20 12.3 ± 4.34 62.8
Palmitic Acid Ethyl Ester 20/20 9.6 ± 3.75 71.0
Stearic acid ethyl ester 20/20 8.0 ± 2.08 75.8
Dihydrosterulic acid ethyl ester 20/20 15.1 ± 6.01 54.4
Tuberculostearic acid ethyl ester 20/20 10.0 ± 3.66 69.8
Arachidic Ethyl Ester 20/20 6.8 ± 1.74 79.5
Behenic acid ethyl ester 20/20 6.7 ± 2.28 79.8
Lignoseric acid ethyl ester 20/20 6.7 ± 1.44 79.8
Sertoic acid ethyl ester 20/20 6.3 ± 2.06 81.0
Montanic Acid Ethyl Ester 20/20 5.6 ± 2.28 83.1
Melisic acid ethyl ester 20/20 5.7 ± 1.06 82.8
Corinomycolic Acid Ethyl Ester 20/20 10.2 ± 3.06 69.2
Omeprazole + Unsaturated fatty acid (E) -deca-2-ene-4,6,8-triinoic acid ethyl ester 20/20 12.8 ± 2.69 61.3
Undecenoic acid ethyl ester 20/20 10.9 ± 1.25 67.1
Hydnocarboxylic Acid Ethyl Ester 20/20 15.0 ± 2.46 54.7
Palmitoleic Acid Ethyl Ester 20/20 6.9 ± 2.14 79.2
Chammuric acid ethyl ester 20/20 11.0 ± 2.34 66.8
Malvalic acid ethyl ester 20/20 10.7 ± 2.37 67.7
Oleic acid ethyl ester 20/20 4.5 ± 1.02 86.4
Ricinoleic acid ethyl ester 20/20 6.5 ± 1.61 80.4
Bacsenic acid ethyl ester 20/20 8.0 ± 2.33 75.8
Linoleic acid ethyl ester 20/20 2.6 ± 0.37 92.1
Crephenic Acid Ethyl Ester 20/20 5.1 ± 1.00 84.6
Dihydrocrephenic acid ethyl ester 20/20 4.2 ± 2.01 87.3
Linolenic acid ethyl ester 20/20 6.1 ± 2.67 81.6
α-linolenic acid ethyl ester 20/20 8.0 ± 1.32 75.8
γ-linolenic acid ethyl ester 20/20 5.8 ± 1.24 82.5
Stearic Acid Ethyl Ester 20/20 6.7 ± 1.19 79.8
Sterkulic acid ethyl ester 20/20 13.5 ± 2.68 59.2
Gadoleic Acid Ethyl Ester 20/20 10.3 ± 3.33 68.9
Eicosatetraenoic acid ethyl ester 20/20 5.9 ± 2.00 82.2
Arachidonic acid ethyl ester 20/20 5.3 ± 1.03 84.0
Eicosapentaenoic acid ethyl ester 20/20 5.4 ± 2.46 83.7
Erucic acid ethyl ester 20/20 10.1 ± 3.25 69.5
Chicoric Acid Ethyl Ester 20/20 5.4 ± 1.69 83.7
Docosapentaenoic Acid Ethyl Ester 20/20 5.2 ± 2.08 84.3
Docosahexaenoic Acid Ethyl Ester 20/20 5.0 ± 1.22 84.9
Nerbornic acid ethyl ester 20/20 9.6 ± 2.84 71.0
The average value P <0.05 and do not differ significantly (Student t-test) 1) omeprazole tablets: CKD up / duodenal ulcer treatment (20 mg as Omeprazole)
표 7 란소프라졸, 판토프라졸, 라베프라졸, 레바프라잔, 일라프라졸 또는 에스오메프라졸과 지방산 에스테르 화합물의 병용 투여에 따른 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%)
대조군 - 43.6±6.34 -
란소프라졸1) 단독 40 18.1±5.82 58.5
란소프라졸+지방산계열 올레산 에틸 에스테르 20/20 10.0±1.94 77.1
리놀레산 에틸 에스테르 20/20 6.4±2.54 85.3
디하이드로크레페닌산 에틸 에스테르 20/20 8.9±3.61 79.6
도코사헥사에노산 에틸 에스테르 20/20 11.3±1.28 74.1
아라키돈산 에틸 에스테르 20/20 7.7±2.41 82.3
판토프라졸2) 단독 40 17.5±4.76 59.9
판토프라졸+지방산계열 올레산 에틸 에스테르 20/20 8.5±1.50 80.5
리놀레산 에틸 에스테르 20/20 5.9±1.24 86.5
디하이드로크레페닌산 에틸 에스테르 20/20 7.6±2.42 82.6
도코사헥사에노산 에틸 에스테르 20/20 9.6±1.28 78.0
아라키돈산 에틸 에스테르 20/20 7.1±2.72 83.7
라베프라졸3) 단독 40 16.7±5.19 61.7
라베프라졸+지방산계열 올레산 에틸 에스테르 20/20 8.0±1.58 81.7
리놀레산 에틸 에스테르 20/20 5.2±1.67 88.1
디하이드로크레페닌산 에틸 에스테르 20/20 7.0±0.94 83.9
도코사헥사에노산 에틸 에스테르 20/20 8.8±3.72 79.8
아라키돈산 에틸 에스테르 20/20 6.7±0.22 84.6
레바프라잔4) 단독 40 15.9±4.66 63.5
레바프라잔+지방산계열 올레산 에틸 에스테르 20/20 6.5±1.75 85.1
리놀레산 에틸 에스테르 20/20 3.7±0.73 91.5
디하이드로크레페닌산 에틸 에스테르 20/20 5.4±1.40 87.6
도코사헥사에노산 에틸 에스테르 20/20 7.1±2.81 83.7
아라키돈산 에틸 에스테르 20/20 4.9±0.67 88.8
일라프라졸5) 단독 40 9.4±3.72 78.4
일라프라졸+지방산계열 올레산 에틸 에스테르 20/20 3.2±0.80 92.7
리놀레산 에틸 에스테르 20/20 1.7±0.33 96.1
디하이드로크레페닌산 에틸 에스테르 20/20 2.5±0.67 94.3
도코사헥사에노산 에틸 에스테르 20/20 3.6±2.43 91.7
아라키돈산 에틸 에스테르 20/20 2.3±0.79 94.7
에스오메프라졸6) 단독 40 13.5±3.26 69.0
에스오메프라졸+지방산계열 올레산 에틸 에스테르 20/20 4.6±1.01 89.4
리놀레산 에틸 에스테르 20/20 2.8±0.51 93.6
디하이드로크레페닌산 에틸 에스테르 20/20 4.2±1.75 90.4
도코사헥사에노산 에틸 에스테르 20/20 5.7±2.09 86.9
아라키돈산 에틸 에스테르 20/20 3.5±0.63 92.0
평균값은 P<0.05와 크게 다르지 않다(Student t-test) 1)란소프라졸정: 안국제약 위/십이지장 궤양 치료제(30 mg as Lansoprazole) 2)판토프라졸정: 한불제약 역류성 식도질환 치료제(20 mg as Pantoprazole) 3)라베프라졸정: 바이넥스 위/십이지장 궤양 치료제(10 mg as Rabeprazole) 4)레바넥스정: 유한양행 궤양 치료제(10 mg as Rebaprazan) 5)일라프라졸정: 일양약품 십이지장 궤양 치료제(10 mg as Ilaprazol) 6)에스메졸 캡슐: 한미약품 위/식도 역류성 질환 치료제(20 mg as Esomeprazole)
TABLE 7 <u> Efficacy of gastritis-gastric ulcer by the combination of lansoprazole, pantoprazole, rabeprazole, revaprazan, ilaprazole or esomeprazole with fatty acid ester compounds
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition
Control - 43.6 ± 6.34 -
Lansoprazole 1) alone 40 18.1 ± 5.82 58.5
Lansoprazole + Fatty Acid Oleic acid ethyl ester 20/20 10.0 ± 1.94 77.1
Linoleic acid ethyl ester 20/20 6.4 ± 2.54 85.3
Dihydrocrephenic acid ethyl ester 20/20 8.9 ± 3.61 79.6
Docosahexaenoic Acid Ethyl Ester 20/20 11.3 ± 1.28 74.1
Arachidonic acid ethyl ester 20/20 7.7 ± 2.41 82.3
Pantoprazole 2) alone 40 17.5 ± 4.76 59.9
Pantoprazole + Fatty Acid Oleic acid ethyl ester 20/20 8.5 ± 1.50 80.5
Linoleic acid ethyl ester 20/20 5.9 ± 1.24 86.5
Dihydrocrephenic acid ethyl ester 20/20 7.6 ± 2.42 82.6
Docosahexaenoic Acid Ethyl Ester 20/20 9.6 ± 1.28 78.0
Arachidonic acid ethyl ester 20/20 7.1 ± 2.72 83.7
Rabeprazole 3) alone 40 16.7 ± 5.19 61.7
Rabeprazole + Fatty Acid Oleic acid ethyl ester 20/20 8.0 ± 1.58 81.7
Linoleic acid ethyl ester 20/20 5.2 ± 1.67 88.1
Dihydrocrephenic acid ethyl ester 20/20 7.0 ± 0.94 83.9
Docosahexaenoic Acid Ethyl Ester 20/20 8.8 ± 3.72 79.8
Arachidonic acid ethyl ester 20/20 6.7 ± 0.22 84.6
Levaprazan 4) alone 40 15.9 ± 4.66 63.5
Levaprazan + fatty acid series Oleic acid ethyl ester 20/20 6.5 ± 1.75 85.1
Linoleic acid ethyl ester 20/20 3.7 ± 0.73 91.5
Dihydrocrephenic acid ethyl ester 20/20 5.4 ± 1.40 87.6
Docosahexaenoic Acid Ethyl Ester 20/20 7.1 ± 2.81 83.7
Arachidonic acid ethyl ester 20/20 4.9 ± 0.67 88.8
Ilaprazole 5) alone 40 9.4 ± 3.72 78.4
Ilaprazole + fatty acid series Oleic acid ethyl ester 20/20 3.2 ± 0.80 92.7
Linoleic acid ethyl ester 20/20 1.7 ± 0.33 96.1
Dihydrocrephenic acid ethyl ester 20/20 2.5 ± 0.67 94.3
Docosahexaenoic Acid Ethyl Ester 20/20 3.6 ± 2.43 91.7
Arachidonic acid ethyl ester 20/20 2.3 ± 0.79 94.7
Someprazole 6) alone 40 13.5 ± 3.26 69.0
Someprazole + fatty acid series Oleic acid ethyl ester 20/20 4.6 ± 1.01 89.4
Linoleic acid ethyl ester 20/20 2.8 ± 0.51 93.6
Dihydrocrephenic acid ethyl ester 20/20 4.2 ± 1.75 90.4
Docosahexaenoic Acid Ethyl Ester 20/20 5.7 ± 2.09 86.9
Arachidonic acid ethyl ester 20/20 3.5 ± 0.63 92.0
The average value P <do not differ greatly from the 0.05 (Student t-test) 1 ) lansoprazole tablets: Anguk Pharmaceuticals up / duodenal ulcer treatment (30 mg as Lansoprazole) 2) pantoprazole joljeong: Hanbul pharmaceutical reflux esophageal disease treatment (20 mg as Pantoprazole ) 3) rabeprazole joljeong: Binex up / duodenal ulcer (10 mg as Rabeprazole) 4) Revanex information: Yuhan ulcer (10 mg as Rebaprazan) 5) ilaprazole information: Ilyang drugs duodenal ulcer drug (10 mg as Ilaprazol) 6) Esmezol Capsule: 20 mg as Esomeprazole (Hanmi Pharm.)
표 6 및 표 7에 나타낸 바와 같이, 올레산 에틸 에스테르, 리놀레산 에틸 에스테르, 디하이드로크레페닌산 에틸 에스테르, 도코사헥사에노산 에틸 에스테르, 아라키돈산 에틸 에스테르 등의 본 발명에 따른 지방산의 에스테르 화합물과 프로톤 펌프 저해제를 병용 투여하는 경우, 프로톤 펌프 저해제 단독 투여시보다 위염-위궤양 억제율이 유의적으로 상승하는 것으로 나타났으며, 특히 리놀레산 에틸 에스테르를 사용한 경우에는 프로톤 펌프 저해제 단독 투여시보다 위염-위궤양 억제율이 20% 이상 상승하는 것으로 나타났다.As shown in Tables 6 and 7, 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%.
따라서, 본 발명에 따른 지방산 또는 이의 에스테르 화합물은 위벽을 보호하여 위염-위궤양의 병변을 억제하는 효과가 뛰어나므로 위벽 보호 및 위장 질환 치료제로서 유용하게 사용될 수 있다.Therefore, 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.
(3) 지방산 계열 화합물과 위점막 보호제의 병용 투여(3) Concomitant administration of fatty acid compounds and gastric mucosa protective agents
상기 실시예 3에서 시험된 지방산 계열 화합물과 위점막 보호제로서 스티렌(동아제약), 미소프로스톨(엘디에스약품)을 중량 기준으로 1:1 병용 투여하는 것을 제외하고는 상기 실시예 2와 동일한 방법으로 위병변 억제 효과를 측정하였다.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.
측정 결과를 표 8 및 표 9에 나타내었다.The measurement results are shown in Table 8 and Table 9.
표 8 스티렌과 지방산 에스테르 화합물의 병용 투여에 따른 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%)
대조군 - 35.3±3.89 -
스티렌1) 40 16.7±4.30 52.7
스티렌+포화지방산계열 부티르산 에틸 에스테르 20/20 25.6±3.87 27.5
카프로산 에틸 에스테르 20/20 25.4±6.49 28.0
카프릴산 에틸 에스테르 20/20 23.4±4.38 33.7
카프르산 에틸 에스테르 20/20 21.9±4.75 38.0
라우르산 에틸 에스테르 20/20 22.1±1.98 37.4
미리스트산 에틸 에스테르 20/20 21.6±3.69 38.8
2,4,6,8-테트라메틸데카논산 에틸 에스테르 20/20 16.5±4.56 53.3
팔미트산 에틸 에스테르 20/20 13.8±7.64 60.9
스테아르산 에틸 에스테르 20/20 12.2±2.38 65.4
디하이드로스테르쿨린산 에틸 에스테르 20/20 19.3±3.54 45.3
튜베르큘로스테아르산 에틸 에스테르 20/20 14.2±2.31 59.8
아라키드산 에틸 에스테르 20/20 11.0±6.91 68.8
베헨산 에틸 에스테르 20/20 10.9±2.48 69.1
리그노세르산 에틸 에스테르 20/20 10.9±3.74 69.1
세로트산 에틸 에스테르 20/20 10.5±1.69 70.3
몬타닌산 에틸 에스테르 20/20 9.8±2.34 72.2
멜리스산 에틸 에스테르 20/20 9.9±2.58 72.0
코리노미콜산 에틸 에스테르 20/20 14.4±3.64 59.2
스티렌+불포화지방산계열 (E)-데카-2-엔-4,6,8-트리이노산 에틸 에스테르 20/20 17.0±3.36 51.8
운데세노산 에틸 에스테르 20/20 15.1±2.38 57.2
히드노카르프산 에틸 에스테르 20/20 19.2±3.33 45.6
팔미톨레산 에틸 에스테르 20/20 11.1±4.56 68.6
차울무그르산 에틸 에스테르 20/20 15.2±2.87 56.9
말발산 에틸 에스테르 20/20 14.9±4.67 57.8
올레산 에틸 에스테르 20/20 8.7±1.33 75.4
리시놀레산 에틸 에스테르 20/20 10.7±1.55 69.7
박센산 에틸 에스테르 20/20 12.2±5.64 65.4
리놀레산 에틸 에스테르 20/20 6.8±2.34 80.7
크레페닌산 에틸 에스테르 20/20 9.3±1.55 73.7
디하이드로크레페닌산 에틸 에스테르 20/20 8.4±2.20 76.2
리놀렌산 에틸 에스테르 20/20 10.3±2.68 70.8
α-리놀렌산 에틸 에스테르 20/20 12.2±8.31 65.4
γ-리놀렌산 에틸 에스테르 20/20 10.0±5.37 71.7
스테아리돈산 에틸 에스테르 20/20 10.9±3.47 69.1
스테르쿨린산 에틸 에스테르 20/20 17.7±1.29 49.9
가돌레산 에틸 에스테르 20/20 14.5±4.51 58.9
에이코사테트라에노산 에틸 에스테르 20/20 10.1±1.26 71.4
아라키돈산 에틸 에스테르 20/20 9.5±2.56 73.1
에이코사펜타에노산 에틸 에스테르 20/20 9.6±1.67 72.8
에루스산 에틸 에스테르 20/20 14.3±7.86 59.5
치코르산 에틸 에스테르 20/20 9.6±3.20 72.8
도코사펜타에노산 에틸 에스테르 20/20 9.4±2.14 73.4
도코사헥사에노산 에틸 에스테르 20/20 9.2±2.68 73.9
네르본산 에틸 에스테르 20/20 13.8±3.66 60.9
평균값은 P<0.05와 크게 다르지 않다(Student t-test) 1)스티렌정: 동아제약 급/만성 위염 치료제(60 mg as Artemisiae argyi Folium 95% EtOH ext.(애엽 추출물))
Table 8 <u> Gastroenteritis-Gastrointestinal Inhibitory Effect of Combination Administration of Styrene and Fatty Acid Ester Compounds </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition
Control - 35.3 ± 3.89 -
Styrene 1) 40 16.7 ± 4.30 52.7
Styrene + Saturated Fatty Acid Butyric acid ethyl ester 20/20 25.6 ± 3.87 27.5
Caproic acid ethyl ester 20/20 25.4 ± 6.49 28.0
Caprylic Acid Ethyl Ester 20/20 23.4 ± 4.38 33.7
Capric acid ethyl ester 20/20 21.9 ± 4.75 38.0
Lauric acid ethyl ester 20/20 22.1 ± 1.98 37.4
Myristic acid ethyl ester 20/20 21.6 ± 3.69 38.8
2,4,6,8-tetramethyldecanoic acid ethyl ester 20/20 16.5 ± 4.56 53.3
Palmitic Acid Ethyl Ester 20/20 13.8 ± 7.64 60.9
Stearic acid ethyl ester 20/20 12.2 ± 2.38 65.4
Dihydrosterulic acid ethyl ester 20/20 19.3 ± 3.54 45.3
Tuberculostearic acid ethyl ester 20/20 14.2 ± 2.31 59.8
Arachidic Ethyl Ester 20/20 11.0 ± 6.91 68.8
Behenic acid ethyl ester 20/20 10.9 ± 2.48 69.1
Lignoseric acid ethyl ester 20/20 10.9 ± 3.74 69.1
Sertoic acid ethyl ester 20/20 10.5 ± 1.69 70.3
Montanic Acid Ethyl Ester 20/20 9.8 ± 2.34 72.2
Melisic acid ethyl ester 20/20 9.9 ± 2.58 72.0
Corinomycolic Acid Ethyl Ester 20/20 14.4 ± 3.64 59.2
Styrene + unsaturated fatty acid series (E) -deca-2-ene-4,6,8-triinoic acid ethyl ester 20/20 17.0 ± 3.36 51.8
Undecenoic acid ethyl ester 20/20 15.1 ± 2.38 57.2
Hydnocarboxylic Acid Ethyl Ester 20/20 19.2 ± 3.33 45.6
Palmitoleic Acid Ethyl Ester 20/20 11.1 ± 4.56 68.6
Chammuric acid ethyl ester 20/20 15.2 ± 2.87 56.9
Malvalic acid ethyl ester 20/20 14.9 ± 4.67 57.8
Oleic acid ethyl ester 20/20 8.7 ± 1.33 75.4
Ricinoleic acid ethyl ester 20/20 10.7 ± 1.55 69.7
Bacsenic acid ethyl ester 20/20 12.2 ± 5.64 65.4
Linoleic acid ethyl ester 20/20 6.8 ± 2.34 80.7
Crephenic Acid Ethyl Ester 20/20 9.3 ± 1.55 73.7
Dihydrocrephenic acid ethyl ester 20/20 8.4 ± 2.20 76.2
Linolenic acid ethyl ester 20/20 10.3 ± 2.68 70.8
α-linolenic acid ethyl ester 20/20 12.2 ± 8.31 65.4
γ-linolenic acid ethyl ester 20/20 10.0 ± 5.37 71.7
Stearic Acid Ethyl Ester 20/20 10.9 ± 3.47 69.1
Sterkulic acid ethyl ester 20/20 17.7 ± 1.29 49.9
Gadoleic Acid Ethyl Ester 20/20 14.5 ± 4.51 58.9
Eicosatetraenoic acid ethyl ester 20/20 10.1 ± 1.26 71.4
Arachidonic acid ethyl ester 20/20 9.5 ± 2.56 73.1
Eicosapentaenoic acid ethyl ester 20/20 9.6 ± 1.67 72.8
Erucic acid ethyl ester 20/20 14.3 ± 7.86 59.5
Chicoric Acid Ethyl Ester 20/20 9.6 ± 3.20 72.8
Docosapentaenoic Acid Ethyl Ester 20/20 9.4 ± 2.14 73.4
Docosahexaenoic Acid Ethyl Ester 20/20 9.2 ± 2.68 73.9
Nerbornic acid ethyl ester 20/20 13.8 ± 3.66 60.9
The average value P <significantly not different from the 0.05 (Student t-test) 1 ) Styrene information: Company grade / chronic gastritis (60 mg as Artemisiae argyi Folium 95 % EtOH ext ( aeyeop extract.))
표 9 미소프로스톨과 지방산 에스테르 화합물의 병용 투여에 따른 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%)
대조군 - 40.5±2.71 -
미소프로스톨1) 40 19.1±3.77 52.8
미소프로스톨+지방산계열 올레산 에틸 에스테르 20/20 12.1±1.53 70.1
리놀레산 에틸 에스테르 20/20 8.6±1.42 78.8
디하이드로크레페닌산 에틸 에스테르 20/20 10.7±2.97 73.6
도코사헥사에노산 에틸 에스테르 20/20 13.8±3.28 65.9
아라키돈산 에틸 에스테르 20/20 12.3±4.51 69.6
평균값은 P<0.05와 크게 다르지 않다(Student t-test) 1)미소프로스톨정: 엘디에스약품 위/십이지장 궤양 치료제(100 mg as Misoprostol)
Table 9 <u> Gastroenteritis-Gastrointestinal Inhibitory Effect of Combination Administration of Misoprostol and Fatty Acid Ester Compounds </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition
Control - 40.5 ± 2.71 -
Misoprostall 1) 40 19.1 ± 3.77 52.8
Microprostol + Fatty Acid Oleic acid ethyl ester 20/20 12.1 ± 1.53 70.1
Linoleic acid ethyl ester 20/20 8.6 ± 1.42 78.8
Dihydrocrephenic acid ethyl ester 20/20 10.7 ± 2.97 73.6
Docosahexaenoic Acid Ethyl Ester 20/20 13.8 ± 3.28 65.9
Arachidonic acid ethyl ester 20/20 12.3 ± 4.51 69.6
The average value P <do not differ greatly from the 0.05 (Student t-test) 1 ) misoprostol tablets: El DS drug up / duodenal ulcer therapeutic agent (100 mg as Misoprostol)
표 8 및 표 9에 나타낸 바와 같이, 올레산 에틸 에스테르, 리놀레산 에틸 에스테르, 디하이드로크레페닌산 에틸 에스테르, 도코사헥사에노산 에틸 에스테르, 아라키돈산 에틸 에스테르 등의 본 발명에 따른 지방산의 에스테르 화합물과 위점막 보호제를 병용 투여하는 경우, 위점막 보호제 단독 투여시보다 위염-위궤양 억제율이 유의적으로 상승하는 것으로 나타났으며, 특히 리놀레산 에틸 에스테르를 사용한 경우에는 위점막 보호제 단독 투여시보다 위염-위궤양 억제율이 20% 이상 상승하는 것으로 나타났다.As shown in Tables 8 and 9, 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. In the case of coadministration with a protective agent, the gastritis-gastric ulcer inhibition rate was significantly higher than that of the gastric mucosal protective agent alone. In particular, when linoleic acid ethyl ester was used, the gastritis-gastric ulcer inhibition rate was 20 higher than that of the gastric mucosal protective agent alone. Rising over%.
따라서, 본 발명에 따른 지방산 또는 이의 에스테르 화합물은 위벽을 보호하여 위염-위궤양의 병변을 억제하는 효과가 뛰어나므로 위벽 보호 및 위장 질환 치료제로서 유용하게 사용될 수 있다.Therefore, 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.
(4) 지방산 계열 화합물과 가스트린 수용체 저해제의 병용 투여(4) Concomitant Administration of Fatty Acid Compounds and Gastrin Receptor Inhibitors
상기 실시예 3에서 시험된 지방산 계열 화합물과 가스트린 수용체 저해제로서 레바미피드(일양약품)를 중량 기준으로 1:1 병용 투여하는 것을 제외하고는 상기 실시예 2와 동일한 방법으로 위병변 억제 효과를 측정하였다.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.
측정 결과를 표 10에 나타내었다.The measurement results are shown in Table 10.
표 10 레바미피드와 지방산 에스테르 화합물의 병용 투여에 따른 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%)
대조군 - 40.5±2.71 -
레바미피드1) 40 18.5±5.06 54.3
레바미피트+지방산계열 올레산 에틸 에스테르 20/20 9.3±1.70 77.0
리놀레산 에틸 에스테르 20/20 6.1±2.26 84.9
디하이드로크레페닌산 에틸 에스테르 20/20 8.4±1.76 79.3
도코사헥사에노산 에틸 에스테르 20/20 10.9±1.54 73.1
아라키돈산 에틸 에스테르 20/20 8.1±3.85 80.0
평균값은 P<0.05와 크게 다르지 않다(Student t-test) 1)레바미피드정: 일양약품 위궤양 치료제(100 mg as Rebamipid)
Table 10 <u> Gastroenteritis-Gastrointestinal Inhibitory Effect of Combination Administration of LevamiFeed and Fatty Acid Ester Compounds </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition
Control - 40.5 ± 2.71 -
Levamifeed 1) 40 18.5 ± 5.06 54.3
Levami Fit + Fatty Acid Oleic acid ethyl ester 20/20 9.3 ± 1.70 77.0
Linoleic acid ethyl ester 20/20 6.1 ± 2.26 84.9
Dihydrocrephenic acid ethyl ester 20/20 8.4 ± 1.76 79.3
Docosahexaenoic Acid Ethyl Ester 20/20 10.9 ± 1.54 73.1
Arachidonic acid ethyl ester 20/20 8.1 ± 3.85 80.0
The average value P <do not differ greatly from the 0.05 (Student t-test) 1 ) rebamipide tablets: Ilyang drugs gastric ulcer treatment (100 mg as Rebamipid)
표 10에 나타낸 바와 같이, 올레산 에틸 에스테르, 리놀레산 에틸 에스테르, 디하이드로크레페닌산 에틸 에스테르, 도코사헥사에노산 에틸 에스테르, 아라키돈산 에틸 에스테르 등의 본 발명에 따른 지방산의 에스테르 화합물과 가스트린 수용체 저해제를 병용 투여하는 경우, 가스트린 수용체 저해제 단독 투여시보다 위염-위궤양 억제율이 유의적으로 상승하는 것으로 나타났으며, 특히 리놀레산 에틸 에스테르를 사용한 경우에는 가스트린 수용체 저해제 단독 투여시보다 위염-위궤양 억제율이 20% 이상 상승하는 것으로 나타났다.As shown in Table 10, 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. In the case of administration, the gastritis-gastric ulcer inhibition rate was significantly higher than that of the gastrin receptor inhibitor alone. Especially, when linoleic acid ethyl ester was used, the gastritis-gastric ulcer inhibition rate was increased by 20% or more. Appeared to be.
따라서, 본 발명에 따른 지방산 또는 이의 에스테르 화합물은 위벽을 보호하여 위염-위궤양의 병변을 억제하는 효과가 뛰어나므로 위벽 보호 및 위장 질환 치료제로서 유용하게 사용될 수 있다.Therefore, 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.
(5) 지방산 계열 화합물과 HEAC 추출물의 병용 투여(5) Concomitant administration of fatty acid compound and HEAC extract
상기 실시예 3에서 시험된 지방산 계열 화합물과 HEAC 추출물을 중량 기준으로 1:1 병용 투여하는 것을 제외하고는 상기 실시예 2와 동일한 방법으로 위병변 억제 효과를 측정하였다.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.
상기 HEAC 추출물은 인진쑥 배진에서 배양된 노루궁뎅이버섯 균사체의 에탄올 추출물로서 다음과 같이 제조하였다. 실시예 1에 기재된 인진쑥 배지에서 배양된 노루궁뎅이버섯의 균사체의 건조물 40.0 g에 80% 에탄올 400.0 mL 정도를 가하여 약 40 ℃에서 24시간 동안 교반추출하고, 약 40 ℃에서 여과하여 제1차 추출물을 얻었다. 얻어진 제1차 추출물은 냉장 보관하였다. 그리고 나서, 제1차추출물 잔유물에 80% 에탄올을 400.0 mL 가하여 약 40 ℃에서 8시간 교반추출하고, 약 40 ℃에서 여과하여 제2차추출물을 얻었다. 마지막으로, 상술한 제조공정에 의하여 제조된 제1차추출물과 제2차추출물을 혼합한 후, 농축시켜 4.4 g(수율 11.0%)을 획득하여 본 실시예의 HEAC 추출물로 사용하였다.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.
측정 결과를 표 11에 나타내었다.The measurement results are shown in Table 11.
표 11 HEAC 추출물과 지방산 에스테르 화합물의 병용 투여에 따른 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%)
대조군 - 38.8±4.17 -
HEAC 추출물1) 40 13.4±3.01 65.4
HEAC추출물+포화지방산계열 부티르산 에틸 에스테르 20/20 23.1±1.32 40.5
카프로산 에틸 에스테르 20/20 22.5±3.65 42.0
카프릴산 에틸 에스테르 20/20 21.8±2.08 43.8
카프르산 에틸 에스테르 20/20 21.3±4.52 45.1
라우르산 에틸 에스테르 20/20 21.5±3.61 44.6
미리스트산 에틸 에스테르 20/20 20.8±2.38 46.4
2,4,6,8-테트라메틸데카논산 에틸 에스테르 20/20 15.1±1.84 61.1
팔미트산 에틸 에스테르 20/20 11.4±1.26 70.6
스테아르산 에틸 에스테르 20/20 9.2±1.03 76.3
디하이드로스테르쿨린산 에틸 에스테르 20/20 18.9±2.94 51.3
튜베르큘로스테아르산 에틸 에스테르 20/20 11.5±1.87 70.4
아라키드산 에틸 에스테르 20/20 7.3±0.67 81.2
베헨산 에틸 에스테르 20/20 7.6±0.38 80.4
리그노세르산 에틸 에스테르 20/20 7.9±0.26 79.6
세로트산 에틸 에스테르 20/20 7.1±1.24 81.7
몬타닌산 에틸 에스테르 20/20 6.8±0.88 82.5
멜리스산 에틸 에스테르 20/20 7.0±0.65 82.0
코리노미콜산 에틸 에스테르 20/20 11.0±1.22 71.6
HEAC추출물+불포화지방산계열 (E)-데카-2-엔-4,6,8-트리이노산 에틸 에스테르 20/20 14.6±3.84 62.4
운데세노산 에틸 에스테르 20/20 14.5±2.46 62.6
히드노카르프산 에틸 에스테르 20/20 19.8±3.27 49.0
팔미톨레산 에틸 에스테르 20/20 7.4±0.99 80.9
차울무그르산 에틸 에스테르 20/20 13.7±1.26 64.7
말발산 에틸 에스테르 20/20 13.4±2.54 65.5
올레산 에틸 에스테르 20/20 5.8±0.61 85.1
리시놀레산 에틸 에스테르 20/20 7.1±1.85 81.7
박센산 에틸 에스테르 20/20 9.3±1.57 76.0
리놀레산 에틸 에스테르 20/20 3.8±0.82 90.2
크레페닌산 에틸 에스테르 20/20 5.3±1.62 86.3
디하이드로크레페닌산 에틸 에스테르 20/20 4.5±0.67 88.4
리놀렌산 에틸 에스테르 20/20 8.6±2.44 77.8
α-리놀렌산 에틸 에스테르 20/20 10.0±3.70 74.2
γ-리놀렌산 에틸 에스테르 20/20 8.7±1.25 77.6
스테아리돈산 에틸 에스테르 20/20 6.7±1.00 82.7
스테르쿨린산 에틸 에스테르 20/20 15.9±3.29 59.0
가돌레산 에틸 에스테르 20/20 11.8±4.18 69.6
에이코사테트라에노산 에틸 에스테르 20/20 8.0±0.67 79.4
아라키돈산 에틸 에스테르 20/20 6.6±1.37 83.0
에이코사펜타에노산 에틸 에스테르 20/20 6.3±0.58 83.8
에루스산 에틸 에스테르 20/20 12.9±2.97 66.8
치코르산 에틸 에스테르 20/20 8.2±1.25 78.9
도코사펜타에노산 에틸 에스테르 20/20 6.9±0.83 82.2
도코사헥사에노산 에틸 에스테르 20/20 6.1±1.31 84.3
네르본산 에틸 에스테르 20/20 11.8±3.90 69.6
평균값은 P<0.05와 크게 다르지 않다(Student t-test) 1)HEAC 추출물: 인진쑥 배지에서 배양한 노루궁뎅이 버섯 균사체의 80% 에탄올 추출물
Table 11 <u> Gastroenteritis-Gastrointestinal Inhibitory Effect by Combination Administration of HEAC Extract and Fatty Acid Ester Compound </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition
Control - 38.8 ± 4.17 -
HEAC extract 1) 40 13.4 ± 3.01 65.4
HEAC extract + saturated fatty acid series Butyric acid ethyl ester 20/20 23.1 ± 1.32 40.5
Caproic acid ethyl ester 20/20 22.5 ± 3.65 42.0
Caprylic Acid Ethyl Ester 20/20 21.8 ± 2.08 43.8
Capric acid ethyl ester 20/20 21.3 ± 4.52 45.1
Lauric acid ethyl ester 20/20 21.5 ± 3.61 44.6
Myristic acid ethyl ester 20/20 20.8 ± 2.38 46.4
2,4,6,8-tetramethyldecanoic acid ethyl ester 20/20 15.1 ± 1.84 61.1
Palmitic Acid Ethyl Ester 20/20 11.4 ± 1.26 70.6
Stearic acid ethyl ester 20/20 9.2 ± 1.03 76.3
Dihydrosterulic acid ethyl ester 20/20 18.9 ± 2.94 51.3
Tuberculostearic acid ethyl ester 20/20 11.5 ± 1.87 70.4
Arachidic Ethyl Ester 20/20 7.3 ± 0.67 81.2
Behenic acid ethyl ester 20/20 7.6 ± 0.38 80.4
Lignoseric acid ethyl ester 20/20 7.9 ± 0.26 79.6
Sertoic acid ethyl ester 20/20 7.1 ± 1.24 81.7
Montanic Acid Ethyl Ester 20/20 6.8 ± 0.88 82.5
Melisic acid ethyl ester 20/20 7.0 ± 0.65 82.0
Corinomycolic Acid Ethyl Ester 20/20 11.0 ± 1.22 71.6
HEAC Extract + Unsaturated Fatty Acid (E) -deca-2-ene-4,6,8-triinoic acid ethyl ester 20/20 14.6 ± 3.84 62.4
Undecenoic acid ethyl ester 20/20 14.5 ± 2.46 62.6
Hydnocarboxylic Acid Ethyl Ester 20/20 19.8 ± 3.27 49.0
Palmitoleic Acid Ethyl Ester 20/20 7.4 ± 0.99 80.9
Chammuric acid ethyl ester 20/20 13.7 ± 1.26 64.7
Malvalic acid ethyl ester 20/20 13.4 ± 2.54 65.5
Oleic acid ethyl ester 20/20 5.8 ± 0.61 85.1
Ricinoleic acid ethyl ester 20/20 7.1 ± 1.85 81.7
Bacsenic acid ethyl ester 20/20 9.3 ± 1.57 76.0
Linoleic acid ethyl ester 20/20 3.8 ± 0.82 90.2
Crephenic Acid Ethyl Ester 20/20 5.3 ± 1.62 86.3
Dihydrocrephenic acid ethyl ester 20/20 4.5 ± 0.67 88.4
Linolenic acid ethyl ester 20/20 8.6 ± 2.44 77.8
α-linolenic acid ethyl ester 20/20 10.0 ± 3.70 74.2
γ-linolenic acid ethyl ester 20/20 8.7 ± 1.25 77.6
Stearic Acid Ethyl Ester 20/20 6.7 ± 1.00 82.7
Sterkulic acid ethyl ester 20/20 15.9 ± 3.29 59.0
Gadoleic Acid Ethyl Ester 20/20 11.8 ± 4.18 69.6
Eicosatetraenoic acid ethyl ester 20/20 8.0 ± 0.67 79.4
Arachidonic acid ethyl ester 20/20 6.6 ± 1.37 83.0
Eicosapentaenoic acid ethyl ester 20/20 6.3 ± 0.58 83.8
Erucic acid ethyl ester 20/20 12.9 ± 2.97 66.8
Chicoric Acid Ethyl Ester 20/20 8.2 ± 1.25 78.9
Docosapentaenoic Acid Ethyl Ester 20/20 6.9 ± 0.83 82.2
Docosahexaenoic Acid Ethyl Ester 20/20 6.1 ± 1.31 84.3
Nerbornic acid ethyl ester 20/20 11.8 ± 3.90 69.6
The average value P <0.05 and do not differ significantly (Student t-test) 1) HEAC extract: 80% of Hericium erinaceus cultured in medium injinssuk mycelium ethanol extract
표 11에 나타낸 바와 같이, 올레산 에틸 에스테르, 리놀레산 에틸 에스테르, 디하이드로크레페닌산 에틸 에스테르, 도코사헥사에노산 에틸 에스테르, 아라키돈산 에틸 에스테르 등의 본 발명에 따른 지방산의 에스테르 화합물과 HEAC 추출물을 병용 투여하는 경우, HEAC 추출물 단독 투여시보다 위염-위궤양 억제율이 유의적으로 상승하는 것으로 나타났으며, 특히 리놀레산 에틸 에스테르를 사용한 경우에는 HEAC 추출물 단독 투여시보다 위염-위궤양 억제율이 25% 이상 상승하는 것으로 나타났다.As shown in Table 11, co-administration of 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. In addition, 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. .
따라서, 본 발명에 따른 지방산 또는 이의 에스테르 화합물은 위벽을 보호하여 위염-위궤양의 병변을 억제하는 효과가 뛰어나므로 위벽 보호 및 위장 질환 치료제로서 유용하게 사용될 수 있다.Therefore, 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.
<실시예 5> 지방산 계열 화합물과 유효약물의 복합제제의 위 보호 효과<Example 5> Gastric protective effect of the combination of the fatty acid-based compound and the active drug
본 발명에 따른 지방산 계열 화합물과 통상적으로 사용되는 위염 또는 위궤양 치료제의 복합제제를 투여하는 경우의 우수한 상승 효과를 확인하기 위하여 다음과 같은 실험을 수행하였다.In order to confirm the excellent synergistic effect of the administration of a combination of a fatty acid-based compound and a gastritis or gastric ulcer therapeutic agent commonly used according to the present invention, the following experiment was performed.
상기 실시예 3에서 시험된 지방산 계열 화합물에 라니티딘, 오메프라졸, 스티렌 또는 HEAC 추출물을 중량 기준으로 1:1로 넣어 복합제제를 제조하고 상기 복합제제를 용량별로 투여하는 것을 제외하고는 상기 실시예 2와 동일한 방법으로 위병변 억제 효과를 측정하였다.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.
측정 결과를 표 12 내지 15에 나타내었다.The measurement results are shown in Tables 12 to 15.
표 12 라니티딘과 지방산 에스테르 화합물의 복합제제의 투여에 따른 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%) ED50
대조군 - 38.0±5.06 - -
라니티딘 단독 40 15.4±4.20 59.5 22.1
20 19.4±2.37 48.9
10 24.3±3.27 36.1
5 28.5±4.25 25.0
2.5 33.8±5.34 11.1
라니티딘+지방산계열 올레산 에틸 에스테르 20/20 7.9±1.28 79.2 14.7
10/10 16.1±3.05 57.6
5/5 22.0±4.72 42.1
2.5/2.5 28.4±2.61 25.3
1.25/1.25 32.0±3.28 15.8
리놀레산 에틸 에스테르 20/20 6.2±0.24 83.7 6.1
10/10 9.7±1.22 74.5
5/5 15.9±3.64 58.2
2.5/2.5 20.1±5.28 47.1
1.25/1.25 26.3±3.84 30.8
디하이드로크레페닌산 에틸 에스테르 20/20 7.0±1.36 81.6 7.3
10/10 11.6±2.45 69.5
5/5 17.0±3.69 55.3
2.5/2.5 21.4±1.57 43.7
1.25/1.25 27.9±5.65 26.6
도코사헥사에노산 에틸 에스테르 20/20 8.7±1.72 77.1 16.6
10/10 17.1±2.95 55.0
5/5 23.9±3.42 37.1
2.5/2.5 29.3±2.69 22.9
1.25/1.25 34.0±5.37 10.5
평균값은 P<0.05와 크게 다르지 않다(Student t-test)
Table 12 <u> Gastroenteritis-Gastrointestinal Inhibitory Effect of Administration of Co-Formulation of Ranitidine with a Fatty Acid Ester Compound </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition ED 50
Control - 38.0 ± 5.06 - -
Ranitidine alone 40 15.4 ± 4.20 59.5 22.1
20 19.4 ± 2.37 48.9
10 24.3 ± 3.27 36.1
5 28.5 ± 4.25 25.0
2.5 33.8 ± 5.34 11.1
Ranitidine + fatty acid series Oleic acid ethyl ester 20/20 7.9 ± 1.28 79.2 14.7
10/10 16.1 ± 3.05 57.6
5/5 22.0 ± 4.72 42.1
2.5 / 2.5 28.4 ± 2.61 25.3
1.25 / 1.25 32.0 ± 3.28 15.8
Linoleic acid ethyl ester 20/20 6.2 ± 0.24 83.7 6.1
10/10 9.7 ± 1.22 74.5
5/5 15.9 ± 3.64 58.2
2.5 / 2.5 20.1 ± 5.28 47.1
1.25 / 1.25 26.3 ± 3.84 30.8
Dihydrocrephenic acid ethyl ester 20/20 7.0 ± 1.36 81.6 7.3
10/10 11.6 ± 2.45 69.5
5/5 17.0 ± 3.69 55.3
2.5 / 2.5 21.4 ± 1.57 43.7
1.25 / 1.25 27.9 ± 5.65 26.6
Docosahexaenoic Acid Ethyl Ester 20/20 8.7 ± 1.72 77.1 16.6
10/10 17.1 ± 2.95 55.0
5/5 23.9 ± 3.42 37.1
2.5 / 2.5 29.3 ± 2.69 22.9
1.25 / 1.25 34.0 ± 5.37 10.5
The mean value is not significantly different from P <0.05 (Student t-test)
표 13 오메프라졸과 지방산 에스테르 화합물의 복합제제의 투여에 따른 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%) ED50
대조군 - 38.4±4.52 - -
오메프라졸 단독 40 14.2±3.62 63.1 17.8
20 18.7±4.76 51.3
10 21.6±2.34 43.8
5 27.8±6.17 27.6
2.5 33.6±3.75 12.5
오메프라졸+지방산계열 올레산 에틸 에스테르 20/20 5.4±1.20 85.9 10.2
10/10 12.6±2.34 67.2
5/5 19.3±5.13 49.7
2.5/2.5 25.5±3.68 33.6
1.25/1.25 29.8±6.73 22.4
리놀레산 에틸 에스테르 20/20 3.0±0.38 92.2 5.3
10/10 7.1±1.33 81.5
5/5 13.8±3.21 64.1
2.5/2.5 19.7±2.68 48.7
1.25/1.25 24.1±4.65 37.2
디하이드로크레페닌산 에틸 에스테르 20/20 4.5±0.97 88.3 6.8
10/10 10.4±1.68 72.9
5/5 16.2±2.84 57.8
2.5/2.5 21.6±5.37 43.8
1.25/1.25 26.4±4.87 31.3
도코사헥사에노산 에틸 에스테르 20/20 5.7±1.08 85.2 13.0
10/10 14.8±2.36 64.5
5/5 21.7±4.51 43.5
2.5/2.5 28.4±1.67 26.0
1.25/1.25 31.0±3.22 19.3
평균값은 P<0.05와 크게 다르지 않다(Student t-test)
Table 13 <u> Gastroenteritis-Gastrointestinal Inhibitory Effect of Omeprazole and Fatty Acid Ester Compounds in Combination Preparation </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition ED 50
Control - 38.4 ± 4.52 - -
Omeprazole alone 40 14.2 ± 3.62 63.1 17.8
20 18.7 ± 4.76 51.3
10 21.6 ± 2.34 43.8
5 27.8 ± 6.17 27.6
2.5 33.6 ± 3.75 12.5
Omeprazole + Fatty Acid Oleic acid ethyl ester 20/20 5.4 ± 1.20 85.9 10.2
10/10 12.6 ± 2.34 67.2
5/5 19.3 ± 5.13 49.7
2.5 / 2.5 25.5 ± 3.68 33.6
1.25 / 1.25 29.8 ± 6.73 22.4
Linoleic acid ethyl ester 20/20 3.0 ± 0.38 92.2 5.3
10/10 7.1 ± 1.33 81.5
5/5 13.8 ± 3.21 64.1
2.5 / 2.5 19.7 ± 2.68 48.7
1.25 / 1.25 24.1 ± 4.65 37.2
Dihydrocrephenic acid ethyl ester 20/20 4.5 ± 0.97 88.3 6.8
10/10 10.4 ± 1.68 72.9
5/5 16.2 ± 2.84 57.8
2.5 / 2.5 21.6 ± 5.37 43.8
1.25 / 1.25 26.4 ± 4.87 31.3
Docosahexaenoic Acid Ethyl Ester 20/20 5.7 ± 1.08 85.2 13.0
10/10 14.8 ± 2.36 64.5
5/5 21.7 ± 4.51 43.5
2.5 / 2.5 28.4 ± 1.67 26.0
1.25 / 1.25 31.0 ± 3.22 19.3
The mean value is not significantly different from P <0.05 (Student t-test)
표 14 스티렌과 지방산 에스테르 화합물의 복합제제의 투여에 따른 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%) ED50
대조군 - 39.6 - -
스티렌 단독 40 16.7±4.30 52.7
스티렌+지방산계열 올레산 에틸 에스테르 20/20 9.0±3.24 77.3 15.8
10/10 17.8±5.67 55.1
5/5 23.4±4.20 40.9
2.5/2.5 30.9±6.37 22.0
1.25/1.25 34.0±3.62 14.1
리놀레산 에틸 에스테르 20/20 7.0±1.37 82.3 6.4
10/10 10.6±3.28 73.2
5/5 16.8±2.69 57.6
2.5/2.5 21.2±6.48 46.5
1.25/1.25 28.5±5.24 28.0
디하이드로크레페닌산 에틸 에스테르 20/20 8.2±2.12 79.3 7.7
10/10 13.5±4.58 65.9
5/5 18.3±3.34 53.8
2.5/2.5 22.7±5.55 42.7
1.25/1.25 29.8±4.16 24.7
도코사헥사에노산 에틸 에스테르 20/20 10.0±2.36 74.7 17.7
10/10 18.6±3.31 53.0
5/5 25.0±5.64 36.9
2.5/2.5 33.2±6.74 16.2
1.25/1.25 35.6±2.68 10.1
평균값은 P<0.05와 크게 다르지 않다(Student t-test)
Table 14 <u> Gastroenteritis-Gastrointestinal Inhibitory Effect of Administration of Combination of Styrene and Fatty Acid Ester Compounds </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition ED 50
Control - 39.6 - -
Styrene sole 40 16.7 ± 4.30 52.7
Styrene + Fatty Acid Oleic acid ethyl ester 20/20 9.0 ± 3.24 77.3 15.8
10/10 17.8 ± 5.67 55.1
5/5 23.4 ± 4.20 40.9
2.5 / 2.5 30.9 ± 6.37 22.0
1.25 / 1.25 34.0 ± 3.62 14.1
Linoleic acid ethyl ester 20/20 7.0 ± 1.37 82.3 6.4
10/10 10.6 ± 3.28 73.2
5/5 16.8 ± 2.69 57.6
2.5 / 2.5 21.2 ± 6.48 46.5
1.25 / 1.25 28.5 ± 5.24 28.0
Dihydrocrephenic acid ethyl ester 20/20 8.2 ± 2.12 79.3 7.7
10/10 13.5 ± 4.58 65.9
5/5 18.3 ± 3.34 53.8
2.5 / 2.5 22.7 ± 5.55 42.7
1.25 / 1.25 29.8 ± 4.16 24.7
Docosahexaenoic Acid Ethyl Ester 20/20 10.0 ± 2.36 74.7 17.7
10/10 18.6 ± 3.31 53.0
5/5 25.0 ± 5.64 36.9
2.5 / 2.5 33.2 ± 6.74 16.2
1.25 / 1.25 35.6 ± 2.68 10.1
The mean value is not significantly different from P <0.05 (Student t-test)
표 15 HEAC 추출물과 지방산 에스테르 화합물의 복합제제의 투여에 따른 위염-위궤양 억제 효과
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%) ED50
대조군 - 35.9±3.80 - -
HEAC 추출물 단독 40 13.4±3.01 65.4
H E A C 추출물+지방산계열 올레산 에틸 에스테르 20/20 6.3±0.62 82.5 10.7
10/10 12.4±1.45 65.5
5/5 18.5±3.62 48.5
2.5/2.5 24.5±4.57 31.8
1.25/1.25 28.6±5.22 20.3
리놀레산 에틸 에스테르 20/20 3.5±0.16 90.3 5.7
10/10 7.3±1.28 79.7
5/5 13.1±2.59 63.5
2.5/2.5 18.6±4.47 48.2
1.25/1.25 23.6±3.65 34.3
디하이드로크레페닌산 에틸 에스테르 20/20 5.1±0.18 85.8 7.4
10/10 10.3±2.91 71.3
5/5 15.8±3.32 56.0
2.5/2.5 20.6±2.56 42.6
1.25/1.25 25.2±1.65 29.8
도코사헥사에노산 에틸 에스테르 20/20 7.5±1.22 79.1 15.0
10/10 15.7±2.94 56.3
5/5 20.9±3.60 41.8
2.5/2.5 27.2±4.28 24.2
1.25/1.25 29.3±3.33 18.4
평균값은 P<0.05와 크게 다르지 않다(Student t-test)
Table 15 <u> Gastroenteritis-Gastrointestinal Inhibitory Effect of Administration of HEC Extract and Fatty Acid Ester Compound
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition ED 50
Control - 35.9 ± 3.80 - -
HEAC extract alone 40 13.4 ± 3.01 65.4
HEAC Extract + Fatty Acids Oleic acid ethyl ester 20/20 6.3 ± 0.62 82.5 10.7
10/10 12.4 ± 1.45 65.5
5/5 18.5 ± 3.62 48.5
2.5 / 2.5 24.5 ± 4.57 31.8
1.25 / 1.25 28.6 ± 5.22 20.3
Linoleic acid ethyl ester 20/20 3.5 ± 0.16 90.3 5.7
10/10 7.3 ± 1.28 79.7
5/5 13.1 ± 2.59 63.5
2.5 / 2.5 18.6 ± 4.47 48.2
1.25 / 1.25 23.6 ± 3.65 34.3
Dihydrocrephenic acid ethyl ester 20/20 5.1 ± 0.18 85.8 7.4
10/10 10.3 ± 2.91 71.3
5/5 15.8 ± 3.32 56.0
2.5 / 2.5 20.6 ± 2.56 42.6
1.25 / 1.25 25.2 ± 1.65 29.8
Docosahexaenoic Acid Ethyl Ester 20/20 7.5 ± 1.22 79.1 15.0
10/10 15.7 ± 2.94 56.3
5/5 20.9 ± 3.60 41.8
2.5 / 2.5 27.2 ± 4.28 24.2
1.25 / 1.25 29.3 ± 3.33 18.4
The mean value is not significantly different from P <0.05 (Student t-test)
표 12 내지 15에 나타낸 바와 같이, 올레산 에틸 에스테르, 리놀레산 에틸 에스테르, 디하이드로크레페닌산 에틸 에스테르, 도코사헥사에노산 에틸 에스테르 등의 본 발명에 따른 지방산의 에스테르 화합물과 기존의 위염-위궤양 치료성분을 복합제제로 제조하여 투여하는 경우, 상기 기존의 치료성분을 단독 투여하는 것보다 위염-위궤양 억제율이 20% 이상 상승하는 것으로 나타났다.As shown in Tables 12 to 15, 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 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.
따라서, 본 발명에 따른 지방산 또는 이의 에스테르 화합물은 위벽을 보호하여 위염-위궤양의 병변을 억제하는 효과가 뛰어나고, 기존의 치료성분과 함께 사용할 때 위염-위궤양의 병변 억제효과를 유의적으로 상승시키므로 위벽 보호 및 위장 질환 치료제로서 유용하게 사용될 수 있다.Therefore, 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.
<비교예> HEAC와 유효약물과의 병용 투여에 따른 위병변 억제 효과<Comparative Example> Effect of inhibiting gastric lesions according to the combination administration of HEAC and an effective drug
본 발명에 따른 지방산계 화합물을 다른 유효 약물과 병용 투여하는 것이, 이들 유효약물을 인진쑥 배지에서 배양한 노루궁뎅이 버섯 균사체 추출물(HEAC)과 병용하는 경우보다 위염 및/또는 위궤양 등의 위장질환 억제 효과가 현저하게 개선됨을 보이기 위하여, 실시예 1에서 제조된 HEAC를 다른 유효약물과 병용 투여하는 경우와, 리노레산 에틸 에스테르와 다른 유효약물을 병용 투여하는 경우의 위장질환 억제효과를 상기 실시예 2와 동일한 방법으로 측정하여, 그 결과를 아래의 표 16에 나타내었다The 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. In order to show that the remarkably improved, the case of the HEAC prepared in Example 1 in combination with other effective drugs, and the combination of linoleic acid ethyl ester and other effective drugs in the gastrointestinal disease inhibitory effect of Example 2 and Measured in the same manner, the results are shown in Table 16 below.
표 16
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 억제율(%)
대조군 - 39.7±5.28 -
HEAC 40 12.8±2.45 67.8
시메티딘 40 18.4±3.10 53.7
HEAC+시메티딘 20/20 12.0±1.47 69.8
리놀레산 에틸 에스테르+시메티딘 20/20 8.6±2.37 79.1
파모티딘 40 16.1±2.52 59.4
HEAC+파모티딘 20/20 11.5±2.96 71.0
리놀레산 에틸 에스테르+파모티딘 20/20 8.4±2.49 79.6
록사티딘 40 15.3±3.89 61.5
HEAC+록사티딘 20/20 10.8±4.53 72.8
리놀레산 에틸 에스테르+록사티딘 20/20 7.8±1.39 81.1
니자티딘 40 15.0±1.05 62.2
HEAC+니자티딘 20/20 9.9±2.66 75.1
리놀레산 에틸 에스테르+니자티딘 20/20 7.0±1.65 93.0
라니티딘 40 16.6±2.74 58.2
HEAC+라니티딘 20/20 11.6±5.40 70.8
리놀레산 에틸 에스테르+라니티딘 20/20 5.0±0.72 87.7
란소프라졸 40 16.2±3.62 59.2
HEAC+란소프라졸 20/20 10.7±2.07 73.0
리놀레산 에틸 에스테르+란소프라졸 20/20 6.4±2.54 85.3
판토프라졸 40 15.5±4.50 61.0
HEAC+판토프라졸 20/20 9.4±3.97 76.3
리놀레산 에틸 에스테르+판토프라졸 20/20 5.9±1.24 86.5
라베프라졸 40 14.9±2.43 62.5
HEAC+라베프라졸 20/20 8.6±2.05 78.3
리놀레산 에틸 에스테르+라베프라졸 20/20 5.2±1.67 88.1
일라프라졸 40 13.0±2.34 67.3
HEAC+일라프라졸 20/20 5.4±1.41 86.4
리놀레산 에틸 에스테르+일라프라졸 20/20 1.7±0.33 96.1
레바프라잔 40 14.3±1.42 64.0
HEAC+레바프라잔 20/20 8.1±1.45 79.6
리놀레산 에틸 에스테르+레바프라잔 20/20 3.7±0.73 91.5
오메프라졸 40 14.1±3.29 64.5
HEAC+오메프라졸 20/20 7.5±1.40 81.1
리놀레산 에틸 에스테르+오메프라졸 20/20 2.6±0.37 92.1
에스오메프라졸 40 13.2±2.57 66.8
HEAC+에스오메프라졸 20/20 6.4±2.55 83.9
리놀레산 에틸 에스테르+에스오메프라졸 2/20 2.8±0.51 93.6
레바미피드 40 18.4±3.69 53.7
HEAC+레바미피드 20/20 11.2±2.88 71.8
리놀레산 에틸 에스테르+레바미피드 20/20 6.1±2.26 84.9
미소프로스톨 40 19.0±1.85 52.1
HEAC+미소프로스톨 20/20 14.5±1.14 63.5
리놀레산 에틸 에스테르+미소프로스톨 20/20 8.6±1.42 78.8
스티렌 40 17.9±3.33 54.9
HEAC+스티렌 20/20 12.8±2.82 67.8
리놀레산 에틸 에스테르+스티렌 20/20 6.8±2.34 80.7
평균값은 P<0.05와 크게 다르지 않다(Student t-test)
Table 16
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) % Inhibition
Control - 39.7 ± 5.28 -
HEAC 40 12.8 ± 2.45 67.8
Cimetidine 40 18.4 ± 3.10 53.7
HEAC + Cimetidine 20/20 12.0 ± 1.47 69.8
Linoleic Acid Ethyl Ester + Cimetidine 20/20 8.6 ± 2.37 79.1
Pamotidine 40 16.1 ± 2.52 59.4
HEAC + Famotidine 20/20 11.5 ± 2.96 71.0
Linoleic Acid Ethyl Ester + Palmotidine 20/20 8.4 ± 2.49 79.6
Roxatidine 40 15.3 ± 3.89 61.5
HEAC + Roxatidine 20/20 10.8 ± 4.53 72.8
Linoleic Acid Ethyl Ester + Roxatidine 20/20 7.8 ± 1.39 81.1
Nizatidine 40 15.0 ± 1.05 62.2
HEAC + Nizatidine 20/20 9.9 ± 2.66 75.1
Linoleic Acid Ethyl Ester + Nizatidine 20/20 7.0 ± 1.65 93.0
Ranitidine 40 16.6 ± 2.74 58.2
HEAC + ranitidine 20/20 11.6 ± 5.40 70.8
Linoleic Acid Ethyl Ester + Ranitidine 20/20 5.0 ± 0.72 87.7
Lansoprazole 40 16.2 ± 3.62 59.2
HEAC + Lansoprazole 20/20 10.7 ± 2.07 73.0
Linoleic Acid Ethyl Ester + Lansoprazole 20/20 6.4 ± 2.54 85.3
Pantoprazole 40 15.5 ± 4.50 61.0
HEAC + Pantoprazole 20/20 9.4 ± 3.97 76.3
Linoleic Acid Ethyl Ester + Pantoprazole 20/20 5.9 ± 1.24 86.5
Rabeprazole 40 14.9 ± 2.43 62.5
HEAC + rabbeprazole 20/20 8.6 ± 2.05 78.3
Linoleic Acid Ethyl Ester + Labeprazole 20/20 5.2 ± 1.67 88.1
Ilaprazole 40 13.0 ± 2.34 67.3
HEAC + Ilaprazole 20/20 5.4 ± 1.41 86.4
Linoleic Acid Ethyl Ester + Ilaprazole 20/20 1.7 ± 0.33 96.1
Levaprazan 40 14.3 ± 1.42 64.0
HEAC + Levaprazan 20/20 8.1 ± 1.45 79.6
Linoleic Acid Ethyl Ester + Levaprazan 20/20 3.7 ± 0.73 91.5
Omeprazole 40 14.1 ± 3.29 64.5
HEAC + Omeprazole 20/20 7.5 ± 1.40 81.1
Linoleic Acid Ethyl Ester + Omeprazole 20/20 2.6 ± 0.37 92.1
Someprazole 40 13.2 ± 2.57 66.8
HEAC + Someprazole 20/20 6.4 ± 2.55 83.9
Linoleic Acid Ethyl Ester + Someprazole 2/20 2.8 ± 0.51 93.6
Levamifeed 40 18.4 ± 3.69 53.7
HEAC + Levi's Feed 20/20 11.2 ± 2.88 71.8
Linoleic Acid Ethyl Ester + LevamiFeed 20/20 6.1 ± 2.26 84.9
Misoprostol 40 19.0 ± 1.85 52.1
HEAC + smile prostrol 20/20 14.5 ± 1.14 63.5
Linoleic Acid Ethyl Ester + Misoprostol 20/20 8.6 ± 1.42 78.8
Styrene 40 17.9 ± 3.33 54.9
HEAC + styrene 20/20 12.8 ± 2.82 67.8
Linoleic Acid Ethyl Ester + Styrene 20/20 6.8 ± 2.34 80.7
The mean value is not significantly different from P <0.05 (Student t-test)
표 16에 나타낸 바와 같이, 기존의 위장질환 치료제를 본 발명에 따른 지방산계 화합물과 병용 투여하는 경우가 이를 HEAC와 병용 투여하는 경우보다 위장질환의 억제 효율이 10% 이상 더 우수한 것으로 나타났다. As shown in Table 16, 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.
<실시예 6> 지방산 계열 화합물과 유효약물의 복합제제의 위염, 위궤양 치료 효과<Example 6> Gastritis, gastric ulcer treatment effect of the combination of fatty acid-based compound and the active drug
본 발명에 따른 지방산 계열 화합물과 기존 위장질환 치료제의 복합제제의 위염-위궤양 치료 효과를 알아보기 위하여 다음과 같은 시험을 수행하였다.In order to determine the effect of gastritis-gastric ulcer treatment of the combination of a fatty acid-based compound and a conventional gastrointestinal disorder therapeutic agent according to the present invention, the following tests were performed.
구체적으로 SDF-SD계 레트 암컷(210±10 g)을 24마리씩 그룹화하여 24시간 절식시킨 다음 150 mM HCl-EtOH(60%)용액 1.5 mL를 경구 투여하여 위염, 위궤양을 유발시켰다. 1시간 후, 하기와 같이 군마다 시료를 1차 경구투여하였다.Specifically, 24 female SDF-SD rats (210 ± 10 g) were fasted for 24 hours, and then orally administered with 150 mL of 150 mM HCl-EtOH (60%) solution to induce gastritis and gastric ulcer. After 1 hour, the samples were first orally administered to each group as follows.
1) 1군(대조군): 시료를 투여하지 않음.1) Group 1 (Control): No sample administered.
2) 2군(비교군 1): 오메프라졸을 생리식염수 3 mL에 현탁하여 40 mg/kg의 용량으로 경구투여함.2) Group 2 (Comparative Group 1): Omeprazole was suspended in 3 mL of saline solution and administered orally at a dose of 40 mg / kg.
3) 3군(비교군 2): 스티렌정(동아제약)을 코팅제를 제거한 후 주성분을 생리식염수 3 mL에 현탁하여 40 mg/kg의 용량으로 경구투여함.3) 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.
4) 4군(시험군 1): 지방산 계열 화합물로서 리놀레산 에틸 에스테르를 생리식염수 3 mL에 현탁하여 40 mg/kg의 용량으로 경구투여함.4) 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.
5) 5군(시험군 2): 지방산 계열 화합물로서 리놀레산 에틸 에스테르와 오메프라졸을 1:1 비율로 혼합하여 제조한 복합제제를 생리식염수 3 mL에 현탁하여 40 mg/kg의 용량으로 경구투여함.5) Group 5 (Test Group 2): 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.
24시간 경과 후, 각 군에서 피험쥐를 8마리씩 희생시킨 후, 실시예 2에 기술한 방법으로 위를 적출하여 궤양 정도를 측정하였다. 나머지 쥐들은 시료를 2차 경구투여하였다.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.
48시간 경과 후, 각 군에서 피험쥐를 8마리씩 희생시킨 후, 위를 적출하여 궤양 정도를 측정하였다. 나머지 쥐들은 시료를 3차 경구투여하였다.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.
72시간 경과 후, 피험쥐를 8마리씩 희생시킨 후, 위를 적출하여 궤양 정도를 측정하였다.After 72 hours, eight rats were sacrificed, and the stomach was extracted to measure the degree of ulceration.
측정 결과를 표 17~19 및 도 2~3에 나타내었다.The measurement results are shown in Tables 17 to 19 and FIGS.
표 17 24시간 후
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 치료율(%)
대조군 40 55.0±5.5 -
오메프라졸 단독 40 34.6±3.5 37.0
스티렌 단독 40 30.4±5.2 44.7
리놀레산 에틸 에스테르 40 26.9±3.3 51.1
리놀레산 에틸 에스테르+오메프라졸 20/20 24.5±2.6 55.3
Table 17 <u> 24 hours later </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) Treatment rate (%)
Control 40 55.0 ± 5.5 -
Omeprazole alone 40 34.6 ± 3.5 37.0
Styrene sole 40 30.4 ± 5.2 44.7
Linoleic acid ethyl ester 40 26.9 ± 3.3 51.1
Linoleic Acid Ethyl Ester + Omeprazole 20/20 24.5 ± 2.6 55.3
표 18 48시간 후
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 치료율(%)
대조군 40 51.7±2.6 6.0
오메프라졸 단독 40 21.6±2.4 58.2
스티렌 단독 40 19.3±1.1 62.6
리놀레산 에틸 에스테르 40 16.3±1.9 68.4
리놀레산 에틸 에스테르+오메프라졸 20/20 13.2±1.3 74.5
Table 18 <u> 48 hours later </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) Treatment rate (%)
Control 40 51.7 ± 2.6 6.0
Omeprazole alone 40 21.6 ± 2.4 58.2
Styrene sole 40 19.3 ± 1.1 62.6
Linoleic acid ethyl ester 40 16.3 ± 1.9 68.4
Linoleic Acid Ethyl Ester + Omeprazole 20/20 13.2 ± 1.3 74.5
표 19 72시간 후
처리군 투여량(mg/kg) 병변면적율(평균±S.E.M., %) 치료율(%)
대조군 40 21.5±1.3 58.4
오메프라졸 단독 40 6.2±0.8 71.1
스티렌 단독 40 6.6±0.6 69.5
리놀레산 에틸 에스테르 40 3.2±0.3 85.0
리놀레산 에틸 에스테르+오메프라졸 20/20 1.1±0.3 94.7
Table 19 <u> 72 hours after </ u>
Treatment group Dose (mg / kg) Lesion area ratio (mean ± SEM,%) Treatment rate (%)
Control 40 21.5 ± 1.3 58.4
Omeprazole alone 40 6.2 ± 0.8 71.1
Styrene sole 40 6.6 ± 0.6 69.5
Linoleic acid ethyl ester 40 3.2 ± 0.3 85.0
Linoleic Acid Ethyl Ester + Omeprazole 20/20 1.1 ± 0.3 94.7
표 17~19 및 도 2~3에 나타낸 바와 같이, 본 발명에 따른 지방산 계열 화합물의 일종인 리놀레산 에틸 에스테르는 단독 투여시 위장질환 발생 후 24시간 이후에 51.5%의 치료율을 나타내고, 72시간 이후에는 85%의 치료율을 나타냄으로써 종래 위장질환 치료제(오메프라졸:37%/71.1%, 스티렌:44.7%/69.5%)보다 우수한 위장질환 치료효과를 나타내며, 종래 위장질환 치료제와 복합하여 투여할 때에는 더욱 높은 치료효과를 나타내었다.As shown in Tables 17 to 19 and FIGS. 2 to 3, 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.
따라서, 본 발명에 따른 지방산 또는 이의 에스테르 화합물은 위벽을 보호하여 위염-위궤양의 병변을 억제하는 효과가 뛰어나고, 위염-위궤양 발생시 치료효과도 뛰어나며, 기존의 치료성분과 함께 사용할 때 위염-위궤양의 병변 억제효과를 유의적으로 상승시키므로 위벽 보호 및 위장 질환 치료제로서 유용하게 사용될 수 있다.Therefore, 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.

Claims (18)

  1. 탄소수 4 내지 40개의 포화 지방산, 탄소수 4 내지 14 또는 20 내지 40개의 포화 지방산의 메틸 또는 에틸 에스테르 화합물, 탄소수 8 내지 30개의 불포화 지방산 및 탄소수 8 내지 16 또는 20 내지 30개의 불포화 지방산의 메틸 또는 에틸 에스테르 화합물로 이루어진 군으로부터 선택되는 1종 이상의 화합물, 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 함유하는 Methyl or ethyl esters of saturated fatty acids having 4 to 40 carbon atoms, methyl or ethyl ester compounds of saturated fatty acids having 4 to 14 or 20 to 40 carbon atoms, unsaturated fatty acids having 8 to 30 carbon atoms and unsaturated fatty acids having 8 to 16 or 20 to 30 carbon atoms At least one compound selected from the group consisting of compounds, or a pharmaceutically acceptable salt thereof containing as an active ingredient
    역류성 식도염, 위염, 십이지장염, 위 궤양, 십이지장 궤양, 비스테로이드성 항염증 약물(NSAID)과 연관된 소화 장애, 비궤양 소화불량, 위식도 역류질환, 가스트린종, 급성 상부 위장 출혈, 스트레스 궤양화, 헬리코박터 파일로리 감염, Zollinger-Ellison 증후군(ZES), Werner's 증후군, 및 전신 비만세포증으로 이루어진 군으로부터 선택되는 위장 질환의 예방 또는 치료용 조성물.Reflux esophagitis, gastritis, duodenitis, gastric ulcer, duodenal ulcer, digestive disorders associated with nonsteroidal anti-inflammatory drugs (NSAIDs), non-ulcer dyspepsia, gastroesophageal reflux disease, gastrinoma, acute upper gastrointestinal bleeding, stress ulceration, A composition for preventing or treating gastrointestinal disorders selected from the group consisting of Helicobacter pylori infection, Zollinger-Ellison syndrome (ZES), Werner's syndrome, and systemic mastocytosis.
  2. 제1항에 있어서,The method of claim 1,
    상기 포화 지방산은 부티르산(Butyric acid), 카프로산(Caproic acid), 카프릴산(Caprylic acid), 카프르산(Capric acid), 라우르산(Lauric acid), 미리스트산(Myristic acid), 테트라메틸데카노산(Tetramethyldecanoic acid), 팔미트산(Palmitic acid), 스테아르산(Stearic acid), 디하이드로스테르쿨린산(Dihydrosterculic acid), 튜베르큘로스테아르산(Tuberculostearic acid), 아라키드산(Arachidic acid), 베헨산(Behenic acid), 리그노세르산(Lignoceric acid), 세로트산(Cerotic acid), 몬타닌산(Montanic acid), 멜리스산(Melissic acid), 및 코리노미콜산(Corynomycolic acid)로 이루어진 군으로부터 선택되는 1종 이상의 것이고,The saturated fatty acid is butyric acid (Butyric acid), caproic acid (Caproic acid), caprylic acid (Caprylic acid), capric acid (Capric acid), lauric acid (Lauric acid), myristic acid (Myristic acid), tetra Tetramethyldecanoic acid, Palmitic acid, Stearic acid, Dihydrosterculic acid, Tuberculostearic acid, Arachidic acid acid, Behenic acid, Lignoceric acid, Cerotic acid, Montanic acid, Melissic acid, and Corinomycolic acid One or more selected from the group,
    상기 불포화 지방산은 디하이드로메트리카리아산(Dehydromatricaria acid), 운데세노산(Undecenoic acid), 히드노카르프산(Hydnocarpic acid), 팔미톨레산(Palmitoleic acid), 차울무그르산(Chaulmoogric acid), 말발산(Malvalic acid), 올레산(Oleic acid), 리시놀레산(Ricinoleic acid), 박센산(Vaccenic acid), 리놀레산(Linoleic acid), 크레페닌산(Crepenynic acid), 디하이드로크레페닌산(Dehydrocrepenynic acid), 리놀렌산(Linolenic acid), 스테아리돈산(Stearidonic acid), 스테르쿨린산(Sterculic acid), 가돌레산(Gadoleic acid), DHLA (Dihomo-γ-Linolenic acid), 에이코사테트라에노산(Eicosatetraenoic acid), 아라키돈산(Arachidonic acid), 에이코사펜타에노산(Eicosapentaenoic acid, EPA), 에루스산(Erucic acid), 치코르산(Cichoric acid), 도코사펜타에노산(Docosapentaenoic acid, DPA), 도코사헥사에노산(Docosahexaenoic acid, DHA), 및 네르본산(Nervonic acid)으로 이루어진 군으로부터 선택되는 1종 이상의 것이고,The unsaturated fatty acid is dehydromatricaria acid (Dehydromatricaria acid), Undecenoic acid (Undecenoic acid), Hydnocarpic acid (Hydnocarpic acid), Palmitoleic acid (Palmitoleic acid), Chaulmoogric acid (Chaulmoogric acid), Mal Malvalic acid, oleic acid, ricinoleic acid, vaccenic acid, linoleic acid, crepenynic acid, dehydrocrepenynic acid, linolenic acid (Linolenic acid), Stearidonic acid, Sterculic acid, Gadoleic acid, DHLA (Dihomo-γ-Linolenic acid), Eicosatetraenoic acid, Arachidone Arachidonic acid, Eicosapentaenoic acid (EPA), Erucic acid, Chicoric acid, Docosapentaenoic acid (DPA), Docosahexaenoic acid (Docosahexaenoic acid, DHA), and nervonic acid Will at least one member selected from,
    상기 포화지방산의 에스테르 화합물은 부티르산 에틸 에스테르(Butyric acid ethyl ester), 카프로산 에틸 에스테르(Caproic acid ethyl ester), 카프릴산 에틸 에스테르(Caprylic acid ethyl ester), 카프르산 에틸 에스테르(Capric acid ethyl ester), 라우르산 에틸 에스테르(Lauric acid ethyl ester), 미리스트산 에틸 에스테르(Myristic acid ethyl ester), 테트라메틸데카노산 에틸 에스테르(Tetramethyl decanoic acid ethyl ester), 디하이드로스테르쿨린산 에틸 에스테르(Dihydrosterculic acid ethyl ester), 튜베르큘로스테아린산 에틸 에스테르(Tuberculostearic acid ethyl ester), 아라키드산 에틸 에스테르(Arachidic acid ethyl ester), 베헨산 에틸 에스테르(Behenic acid ethyl ester), 리그노세르산 에틸 에스테르(Lignoceric acid ethyl ester), 세로트산 에틸 에스테르(Cerotic acid ethyl ester), 몬타닌산 에틸 에스테르(Montanic acid ethyl ester), 멜리스산 에틸 에스테르(Melissic acid ethyl ester), 및 코리노미콜산 에틸 에스테르(Corynomycolic acid ethyl ester)로 이루어진 군으로부터 선택되는 1종 이상의 것이며,The ester compound of saturated fatty acid is butyric acid ethyl ester, caproic acid ethyl ester, caprylic acid ethyl ester, capric acid ethyl ester ), Lauric acid ethyl ester, myristic acid ethyl ester, tetramethyl decanoic acid ethyl ester, dihydrosterculic acid ethyl ester acid ethyl ester, Tuberculostearic acid ethyl ester, Arachidic acid ethyl ester, Behenic acid ethyl ester, Lignoceric acid ethyl ester, cerotic acid ethyl ester, montanic acid ethyl ester, meli Acid ethyl ester (Melissic acid ethyl ester), and Corey nominal cholic acid ethyl ester will be at least one selected from the group consisting of (Corynomycolic acid ethyl ester),
    상기 불포화 지방산의 에스테르 화합물은 데카-2-엔-4,6,8-트리이노산 에틸 에스테르((E)-deca-2-en-4,6,8-triynoic acid ethyl ester), 운데세노산 에틸 에스테르(Undecenoic acid ethyl ester), 히드노카르프산 에틸 에스테르(Hydnocarpic acid ethyl ester), 팔미톨레산 에틸 에스테르(Palmitoleic acid ethyl ester), 차울무그르산 에틸 에스테르(Chaulmoogric acid ethyl ester), 말발산 에틸 에스테르(Malvalic acid ethyl ester), 올레산 에틸 에스테르(Oleic acid ethyl ester), 리시놀레산 에틸 에스테르(Ricinoleic acid ethyl ester), 박센산 에틸 에스테르(Vaccenic acid ethyl ester), 리놀레산 에틸 에스테르(Linoleic acid ethyl ester), 크레페닌산 에틸 에스테르(Crepenynic acid ethyl ester), 디하이드로크레페닌산 에틸 에스테르(Dehydrocrepenynic acid ethyl ester), 스테아리돈산 에틸 에스테르(Stearidonic acid ethyl ester), 스테르쿨린산 에틸 에스테르(Sterculic acid ethyl ester), 가돌레산 에틸 에스테르(Gadoleic acid ethyl ester), 에이코사테트라에노산 에틸 에스테르(Eicosatetraenoic acid ethyl ester), 아라키돈산 에틸 에스테르(Arachidonic acid ethyl ester), 에이코사펜타에노산 에틸 에스테르(Eicosapentaenoic acid ethyl ester), 에루스산 에틸 에스테르(Erucic acid ethyl ester), 치코르산 에틸 에스테르(Cichoric acid ethyl ester), 도코사펜타에노산 에틸 에스테르(Docosapentaenoic acid ethyl ester), 도코사헥사에노산 에틸 에스테르(Docosahexaenoic acid ethyl ester), 및 네르본산 에틸 에스테르(Nervonic acid ethyl ester)로 이루어진 군으로부터 선택되는 1종 이상인 것을 특징으로 하는 위장 질환의 예방 또는 치료용 조성물.The ester compound of the unsaturated fatty acid is deca-2-ene-4,6,8-triinoic acid ethyl ester ((E) -deca-2-en-4,6,8-triynoic acid ethyl ester), ethyl undecenoic acid Undecenoic acid ethyl ester, Hydnocarpic acid ethyl ester, Palmitoleic acid ethyl ester, Chaulmoogric acid ethyl ester, Malvalic acid ethyl ester (Malvalic acid ethyl ester), oleic acid ethyl ester, ricinoleic acid ethyl ester, vaccenic acid ethyl ester, linoleic acid ethyl ester, Crepenynic acid ethyl ester, Dehydrocrepenynic acid ethyl ester, Stearidonic acid ethyl ester, Steculinic acid ethyl ester rculic acid ethyl ester, gadoleic acid ethyl ester, eicosatetraenoic acid ethyl ester, arachidonic acid ethyl ester, eicosapentaenoic acid ethyl ester Eicosapentaenoic acid ethyl ester, Erucic acid ethyl ester, Chicoric acid ethyl ester, Docosapentaenoic acid ethyl ester, Docosahexaenoic acid ethyl ester (Docosahexaenoic acid ethyl ester), and Nervonic acid ethyl ester (Nervonic acid ethyl ester) The composition for the prevention or treatment of gastrointestinal diseases, characterized in that at least one member selected from the group consisting of.
  3. 올레산, 리놀레산, 디하이드로크레페닌산, 도코사헥사에노산, 아라키돈산, 올레산 에틸 에스테르, 리놀레산 에틸 에스테르, 디하이드로크레페닌산 에틸 에스테르, 도코사헥사에노산 에틸 에스테르 및 아라키돈산 에틸 에스테르로 이루어진 군으로부터 선택되는 1종 이상, 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 Selected from the group consisting of oleic acid, linoleic acid, dihydrocrefenic acid, docosahexaenoic acid, arachidonic acid, oleic acid ethyl ester, linoleic acid ethyl ester, dihydrocrefeninic acid ethyl ester, docosahexaenoic acid ethyl ester and arachidonic acid ethyl ester Containing at least one, or a pharmaceutically acceptable salt thereof as an active ingredient
    역류성 식도염, 위염, 십이지장염, 위 궤양, 십이지장 궤양, 비스테로이드성 항염증 약물(NSAID)과 연관된 소화 장애, 비궤양 소화불량, 위식도 역류질환, 가스트린종, 급성 상부 위장 출혈, 스트레스 궤양화, 헬리코박터 파일로리 감염, Zollinger-Ellison 증후군(ZES), Werner's 증후군, 및 전신 비만세포증으로 이루어진 군으로부터 선택되는 위장 질환의 예방 또는 치료용 조성물.Reflux esophagitis, gastritis, duodenitis, gastric ulcer, duodenal ulcer, digestive disorders associated with nonsteroidal anti-inflammatory drugs (NSAIDs), non-ulcer dyspepsia, gastroesophageal reflux disease, gastrinoma, acute upper gastrointestinal bleeding, stress ulceration, A composition for preventing or treating gastrointestinal disorders selected from the group consisting of Helicobacter pylori infection, Zollinger-Ellison syndrome (ZES), Werner's syndrome, and systemic mastocytosis.
  4. 리놀레산, 리놀레산 에스테르 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 함유하는 Linoleic acid, linoleic acid ester or a pharmaceutically acceptable salt thereof as an active ingredient
    역류성 식도염, 위염, 십이지장염, 위 궤양, 십이지장 궤양, 비스테로이드성 항염증 약물(NSAID)과 연관된 소화 장애, 비궤양 소화불량, 위식도 역류질환, 가스트린종, 급성 상부 위장 출혈, 스트레스 궤양화, 헬리코박터 파일로리 감염, Zollinger-Ellison 증후군(ZES), Werner's 증후군, 및 전신 비만세포증으로 이루어진 군으로부터 선택되는 위장 질환의 예방 또는 치료용 조성물.Reflux esophagitis, gastritis, duodenitis, gastric ulcer, duodenal ulcer, digestive disorders associated with nonsteroidal anti-inflammatory drugs (NSAIDs), non-ulcer dyspepsia, gastroesophageal reflux disease, gastrinoma, acute upper gastrointestinal bleeding, stress ulceration, A composition for preventing or treating gastrointestinal disorders selected from the group consisting of Helicobacter pylori infection, Zollinger-Ellison syndrome (ZES), Werner's syndrome, and systemic mastocytosis.
  5. 탄소수 3 내지 40개의 포화 지방산, 상기 포화지방산의 메틸 또는 에틸 에스테르 화합물, 탄소수 8 내지 30개의 불포화 지방산 및 상기 불포화 지방산의 메틸 또는 에틸 에스테르 화합물로 이루어진 군에서 선택된 1종 이상의 화합물, 또는 이의 약학적으로 허용 가능한 염(제1 성분), 및At least one compound selected from the group consisting of saturated fatty acids having 3 to 40 carbon atoms, methyl or ethyl ester compounds of the saturated fatty acids, unsaturated fatty acids having 8 to 30 carbon atoms and methyl or ethyl ester compounds of the unsaturated fatty acids, or pharmaceutically thereof Acceptable salts (first component), and
    H2 수용체 길항제, 프로톤 펌프 저해제, 가스트린 수용체 저해제, 위점막 보호제 및 인진쑥 배지에서 배양된 노루궁뎅이 버섯 균사체(Hericium erinaceum Hypha Cultivated with Artemisia capillaries, HEAC) 추출물로 이루어진 군에서 선택된 1종 이상(제2 성분)을 유효성분으로 함유하는 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) ) As an active ingredient
    역류성 식도염, 위염, 십이지장염, 위 궤양, 십이지장 궤양, 비스테로이드성 항염증 약물(NSAID)과 연관된 소화 장애, 비궤양 소화불량, 위식도 역류질환, 가스트린종, 급성 상부 위장 출혈, 스트레스 궤양화, 헬리코박터 파일로리 감염, Zollinger-Ellison 증후군(ZES), Werner's 증후군, 및 전신 비만세포증으로 이루어진 군으로부터 선택되는 위장 질환의 예방 또는 치료용 조성물.Reflux esophagitis, gastritis, duodenitis, gastric ulcer, duodenal ulcer, digestive disorders associated with nonsteroidal anti-inflammatory drugs (NSAIDs), non-ulcer dyspepsia, gastroesophageal reflux disease, gastrinoma, acute upper gastrointestinal bleeding, stress ulceration, A composition for preventing or treating gastrointestinal disorders selected from the group consisting of Helicobacter pylori infection, Zollinger-Ellison syndrome (ZES), Werner's syndrome, and systemic mastocytosis.
  6. 제5항에 있어서,The method of claim 5,
    상기 포화 지방산은 부티르산(Butyric acid), 카프로산(Caproic acid), 카프릴산(Caprylic acid), 카프르산(Capric acid), 라우르산(Lauric acid), 미리스트산(Myristic acid), 테트라메틸데카노산(Tetramethyldecanoic acid), 팔미트산(Palmitic acid), 스테아르산(Stearic acid), 디하이드로스테르쿨린산(Dihydrosterculic acid), 튜베르큘로스테아르산(Tuberculostearic acid), 아라키드산(Arachidic acid), 베헨산(Behenic acid), 리그노세르산(Lignoceric acid), 세로트산(Cerotic acid), 몬타닌산(Montanic acid), 멜리스산(Melissic acid), 및 코리노미콜산(Corynomycolic acid)로 이루어진 군에서 선택된 1종 이상의 것이고,The saturated fatty acid is butyric acid (Butyric acid), caproic acid (Caproic acid), caprylic acid (Caprylic acid), capric acid (Capric acid), lauric acid (Lauric acid), myristic acid (Myristic acid), tetra Tetramethyldecanoic acid, Palmitic acid, Stearic acid, Dihydrosterculic acid, Tuberculostearic acid, Arachidic acid acid, Behenic acid, Lignoceric acid, Ceotic acid, Montanic acid, Monticic acid, Melissic acid, and Corinomycolic acid At least one selected from the group,
    상기 불포화 지방산은 디하이드로메트리카리아산(Dehydromatricaria acid), 운데세노산(Undecenoic acid), 히드노카르프산(Hydnocarpic acid), 팔미톨레산(Palmitoleic acid), 차울무그르산(Chaulmoogric acid), 말발산(Malvalic acid), 올레산(Oleic acid), 리시놀레산(Ricinoleic acid), 박센산(Vaccenic acid), 리놀레산(Linoleic acid), 크레페닌산(Crepenynic acid), 디하이드로크레페닌산(Dehydrocrepenynic acid), 리놀렌산(Linolenic acid), 스테아리돈산(Stearidonic acid), 스테르쿨린산(Sterculic acid), 가돌레산(Gadoleic acid), DHLA (Dihomo-γ-Linolenic acid), 에이코사테트라에노산(Eicosatetraenoic acid), 아라키돈산(Arachidonic acid), 에이코사펜타에노산(Eicosapentaenoic acid, EPA), 에루스산(Erucic acid), 치코르산(Cichoric acid), 도코사펜타에노산(Docosapentaenoic acid, DPA), 도코사헥사에노산(Docosahexaenoic acid, DHA), 및 네르본산(Nervonic acid)으로 이루어진 군에서 선택된 1종 이상의 것이고,The unsaturated fatty acid is dehydromatricaria acid (Dehydromatricaria acid), Undecenoic acid (Undecenoic acid), Hydnocarpic acid (Hydnocarpic acid), Palmitoleic acid (Palmitoleic acid), Chaulmoogric acid (Chaulmoogric acid), Mal Malvalic acid, oleic acid, ricinoleic acid, vaccenic acid, linoleic acid, crepenynic acid, dehydrocrepenynic acid, linolenic acid (Linolenic acid), Stearidonic acid, Sterculic acid, Gadoleic acid, DHLA (Dihomo-γ-Linolenic acid), Eicosatetraenoic acid, Arachidone Arachidonic acid, Eicosapentaenoic acid (EPA), Erucic acid, Chicoric acid, Docosapentaenoic acid (DPA), Docosahexaenoic acid (Docosahexaenoic acid, DHA), and nervonic acid These will stand more than one kind,
    상기 포화지방산의 에스테르 화합물은 부티르산 에틸 에스테르(Butyric acid ethyl ester), 카프로산 에틸 에스테르(Caproic acid ethyl ester), 카프릴산 에틸 에스테르(Caprylic acid ethyl ester), 카프르산 에틸 에스테르(Capric acid ethyl ester), 라우르산 에틸 에스테르(Lauric acid ethyl ester), 미리스트산 에틸 에스테르(Myristic acid ethyl ester), 테트라메틸데카노산 에틸 에스테르(Tetramethyl decanoic acid ethyl ester), 팔미트산 에틸 에스테르(Palmitic acid ethyl ester), 스테아르산 에틸 에스테르(Stearic acid ethyl ester), 디하이드로스테르쿨린산 에틸 에스테르(Dihydrosterculic acid ethyl ester), 튜베르큘로스테아린산 에틸 에스테르(Tuberculostearic acid ethyl ester), 아라키드산 에틸 에스테르(Arachidic acid ethyl ester), 베헨산 에틸 에스테르(Behenic acid ethyl ester), 리그노세르산 에틸 에스테르(Lignoceric acid ethyl ester), 세로트산 에틸 에스테르(Cerotic acid ethyl ester), 몬타닌산 에틸 에스테르(Montanic acid ethyl ester), 멜리스산 에틸 에스테르(Melissic acid ethyl ester), 및 코리노미콜산 에틸 에스테르(Corynomycolic acid ethyl ester)로 이루어진 군에서 선택된 것이고,The ester compound of saturated fatty acid is butyric acid ethyl ester, caproic acid ethyl ester, caprylic acid ethyl ester, capric acid ethyl ester ), Lauric acid ethyl ester, myristic acid ethyl ester, tetramethyl decanoic acid ethyl ester, palmitic acid ethyl ester ), Stearic acid ethyl ester, dihydrosterculic acid ethyl ester, tuberculostearic acid ethyl ester, arachidic acid ester ethyl ester, Behenic acid ethyl ester, Lignoceric acid ethyl ester, It is selected from the group consisting of cerotic acid ethyl ester, montanic acid ethyl ester, melissic acid ethyl ester, and corynomycolic acid ethyl ester. ,
    상기 불포화 지방산의 에스테르 화합물은 데카-2-엔-4,6,8-트리이노산 에틸 에스테르((E)-deca-2-en-4,6,8-triynoic acid ethyl ester), 운데세노산 에틸 에스테르(Undecenoic acid ethyl ester), 히드노카르프산 에틸 에스테르(Hydnocarpic acid ethyl ester), 팔미톨레산 에틸 에스테르(Palmitoleic acid ethyl ester), 차울무그르산 에틸 에스테르(Chaulmoogric acid ethyl ester), 말발산 에틸 에스테르(Malvalic acid ethyl ester), 올레산 에틸 에스테르(Oleic acid ethyl ester), 리시놀레산 에틸 에스테르(Ricinoleic acid ethyl ester), 박센산 에틸 에스테르(Vaccenic acid ethyl ester), 리놀레산 에틸 에스테르(Linoleic acid ethyl ester), 크레페닌산 에틸 에스테르(Crepenynic acid ethyl ester), 디하이드로크레페닌산 에틸 에스테르(Dehydrocrepenynic acid ethyl ester), 리놀렌산 에틸 에스테르(Linolenic acid ethyl ester), 스테아리돈산 에틸 에스테르(Stearidonic acid ethyl ester), 스테르쿨린산 에틸 에스테르(Sterculic acid ethyl ester), 가돌레산 에틸 에스테르(Gadoleic acid ethyl ester), 에이코사테트라에노산 에틸 에스테르(Eicosatetraenoic acid ethyl ester), 아라키돈산 에틸 에스테르(Arachidonic acid ethyl ester), 에이코사펜타에노산 에틸 에스테르(Eicosapentaenoic acid ethyl ester), 에루스산 에틸 에스테르(Erucic acid ethyl ester), 치코르산 에틸 에스테르(Cichoric acid ethyl ester), 도코사펜타에노산 에틸 에스테르(Docosapentaenoic acid ethyl ester), 도코사헥사에노산 에틸 에스테르(Docosahexaenoic acid ethyl ester), 및 네르본산 에틸 에스테르(Nervonic acid ethyl ester)로 이루어진 군에서 선택된 1종 이상인 것을 특징으로 하는 위장 질환의 예방 또는 치료용 조성물.The ester compound of the unsaturated fatty acid is deca-2-ene-4,6,8-triinoic acid ethyl ester ((E) -deca-2-en-4,6,8-triynoic acid ethyl ester), ethyl undecenoic acid Undecenoic acid ethyl ester, Hydnocarpic acid ethyl ester, Palmitoleic acid ethyl ester, Chaulmoogric acid ethyl ester, Malvalic acid ethyl ester (Malvalic acid ethyl ester), oleic acid ethyl ester, ricinoleic acid ethyl ester, vaccenic acid ethyl ester, linoleic acid ethyl ester, Crepenynic acid ethyl ester, dehydrocrepenynic acid ethyl ester, linolenic acid ethyl ester, stearic acid ethyl ester acid ethyl ester, Sterculic acid ethyl ester, Gadoleic acid ethyl ester, Eicosatetraenoic acid ethyl ester, Arachidonic acid ethyl ester ethyl ester, Eicosapentaenoic acid ethyl ester, Erucic acid ethyl ester, Chicoric acid ethyl ester, Docosapentaenoic acid ethyl ester (Docosapentaenoic acid ethyl ester), docosahexaenoic acid ethyl ester (Docosahexaenoic acid ethyl ester), and a composition for the prevention or treatment of gastrointestinal diseases, characterized in that at least one member selected from the group consisting of Nervonic acid ethyl ester (Nervonic acid ethyl ester). .
  7. 제5항에 있어서, 상기 제1 성분은 리놀레산, 리놀레산 에스테르 또는 이들의 약학적으로 허용가능한 염인 것을 특징으로 하는 위장 질환의 예방 또는 치료용 조성물.The method of claim 5, wherein the first component is linoleic acid, linoleic acid ester or a pharmaceutically acceptable salt thereof composition for the prevention or treatment of gastrointestinal diseases.
  8. 제5항에 있어서,The method of claim 5,
    상기 H2 수용체 길항제는 시메티딘, 라니티딘, 파모티딘, 록사티딘, 니자티딘, 및 이들의 약학적으로 허용 가능한 염, 이성질체 및 이성질체의 염으로 이루어진 군에서 선택된 1종 이상의 것이고,The H 2 receptor antagonist is at least one selected from the group consisting of cimetidine, ranitidine, pamotidine, roxatidine, nizatidine, and salts of pharmaceutically acceptable salts, isomers and isomers thereof,
    상기 프로톤 펌프 저해제는 오메프라졸, 란소프라졸, 판토프라졸, 라베프라졸, 레바프라잔, 일라프라졸, 파리프라졸, 레미노프라졸, 및 이들의 약학적으로 허용 가능한 염, 이들의 거울상이성질체, 및 상기 거울상이성질체의 약학적으로 허용 가능한 염으로 이루어진 군에서 선택된 1종 이상의 것이고,The proton pump inhibitors are omeprazole, lansoprazole, pantoprazole, labeprazole, revaprazan, ilaprazole, parrazole, reminoprazole, and pharmaceutically acceptable salts thereof, enantiomers thereof, and the enantiomer At least one member selected from the group consisting of pharmaceutically acceptable salts of isomers,
    상기 가스트린 수용체 저해제는 레바미피드 및 이의 약학적으로 허용 가능한 염으로 이루어진 군에서 선택된 1종 이상의 것이고,The gastrin receptor inhibitor is at least one selected from the group consisting of levamifeed and its pharmaceutically acceptable salts,
    상기 위점막 보호제는 미소프로스톨, 이의 약학적으로 허용 가능한 염, 및 애엽(Artemisiae Argyi Folium) 추출물로 이루어진 군에서 선택된 1종 이상의 것이며,The gastric mucosa protective agent is at least one selected from the group consisting of misoprostol, a pharmaceutically acceptable salt thereof, and Artemisiae Argyi Folium extract,
    상기 인진쑥 배지에서 배양된 노루궁뎅이 버섯 균사체(Hericium erinaceum Hypha Cultivated with Artemisia capillaries, HEAC) 추출물은 인진쑥 배지에서 배양된 노루궁뎅이 버섯 균사체를 물, 탄소수 1 내지 5의 알코올(25 내지 100 v/v%), 헥산, 클로로포름, 염화메틸렌, 아세토니트릴, 아세톤 및 에틸아세테이트로 이루어진 군에서 선택된 1종 이상의 용매로 추출하여 얻어진 것이거나, 상기 얻어진 추출물에 탄소수 1 내지 5의 알코올(25 내지 100 v/v%), 헥산, 염화메틸렌, 및 에틸아세테이트로 이루어진 군에서 선택된 1종 이상을 추가로 가하여 얻어지는 것임을 특징으로 하는 위장 질환의 예방 또는 치료용 조성물.Helicium erinaceum Hypha Cultivated with Artemisia capillaries (HEAC) extracts cultured in the Artemisia agar medium are water, alcohols having 1 to 5 carbon atoms (25 to 100 v / v%). , Obtained by extraction with one or more solvents selected from the group consisting of hexane, chloroform, methylene chloride, acetonitrile, acetone and ethyl acetate, or an alcohol having 1 to 5 carbon atoms (25 to 100 v / v%) , Hexane, methylene chloride, and ethylacetate is a composition for the prevention or treatment of gastrointestinal diseases, characterized in that obtained by further adding one or more selected from the group consisting of.
  9. 제5항에 있어서, 상기 제1 성분과 제2 성분은 하나의 제형으로 제제화되어 한번에 투여되는 형태이거나, 각각 제제화되어 별도로 투여되는 형태인 것을 특징으로 하는 위장 질환의 예방 또는 치료용 조성물.The composition for preventing or treating gastrointestinal diseases according to claim 5, wherein the first component and the second component are formulated in one formulation and administered at one time, or each formulated and administered separately.
  10. 탄소수 4 내지 40개의 포화 지방산, 탄소수 4 내지 14 또는 20 내지 40개의 포화 지방산의 메틸 또는 에틸 에스테르 화합물, 탄소수 8 내지 30개의 불포화 지방산 및 탄소수 8 내지 16 또는 20 내지 30개의 불포화 지방산의 메틸 또는 에틸 에스테르 화합물로 이루어진 군으로부터 선택되는 1종 이상의 화합물, 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 함유하는 위벽 보호용 조성물.Methyl or ethyl esters of saturated fatty acids containing 4 to 40 carbon atoms, methyl or ethyl ester compounds of saturated fatty acids containing 4 to 14 or 20 to 40 carbon atoms, unsaturated fatty acids containing 8 to 30 carbon atoms and unsaturated fatty acids containing 8 to 16 or 20 to 30 carbon atoms A composition for protecting the stomach wall, which contains at least one compound selected from the group consisting of compounds, or a pharmaceutically acceptable salt thereof as an active ingredient.
  11. 제10항에 있어서,The method of claim 10,
    상기 포화 지방산은 부티르산(Butyric acid), 카프로산(Caproic acid), 카프릴산(Caprylic acid), 카프르산(Capric acid), 라우르산(Lauric acid), 미리스트산(Myristic acid), 테트라메틸데카노산(Tetramethyldecanoic acid), 팔미트산(Palmitic acid), 스테아르산(Stearic acid), 디하이드로스테르쿨린산(Dihydrosterculic acid), 튜베르큘로스테아르산(Tuberculostearic acid), 아라키드산(Arachidic acid), 베헨산(Behenic acid), 리그노세르산(Lignoceric acid), 세로트산(Cerotic acid), 몬타닌산(Montanic acid), 멜리스산(Melissic acid), 및 코리노미콜산(Corynomycolic acid)로 이루어진 군으로부터 선택되는 1종 이상의 것이고,The saturated fatty acid is butyric acid (Butyric acid), caproic acid (Caproic acid), caprylic acid (Caprylic acid), capric acid (Capric acid), lauric acid (Lauric acid), myristic acid (Myristic acid), tetra Tetramethyldecanoic acid, Palmitic acid, Stearic acid, Dihydrosterculic acid, Tuberculostearic acid, Arachidic acid acid, Behenic acid, Lignoceric acid, Cerotic acid, Montanic acid, Melissic acid, and Corinomycolic acid One or more selected from the group,
    상기 불포화 지방산은 디하이드로메트리카리아산(Dehydromatricaria acid), 운데세노산(Undecenoic acid), 히드노카르프산(Hydnocarpic acid), 팔미톨레산(Palmitoleic acid), 차울무그르산(Chaulmoogric acid), 말발산(Malvalic acid), 올레산(Oleic acid), 리시놀레산(Ricinoleic acid), 박센산(Vaccenic acid), 리놀레산(Linoleic acid), 크레페닌산(Crepenynic acid), 디하이드로크레페닌산(Dehydrocrepenynic acid), 리놀렌산(Linolenic acid), 스테아리돈산(Stearidonic acid), 스테르쿨린산(Sterculic acid), 가돌레산(Gadoleic acid), DHLA(Dihomo-γ-Linolenic acid), 에이코사테트라에노산(Eicosatetraenoic acid), 아라키돈산(Arachidonic acid), 에이코사펜타에노산(Eicosapentaenoic acid, EPA), 에루스산(Erucic acid), 치코르산(Cichoric acid), 도코사펜타에노산(Docosapentaenoic acid, DPA), 도코사헥사에노산(Docosahexaenoic acid, DHA), 및 네르본산(Nervonic acid)으로 이루어진 군으로부터 선택되는 1종 이상의 것이고,The unsaturated fatty acid is dehydromatricaria acid (Dehydromatricaria acid), Undecenoic acid (Undecenoic acid), Hydnocarpic acid (Hydnocarpic acid), Palmitoleic acid (Palmitoleic acid), Chaulmoogric acid (Chaulmoogric acid), Mal Malvalic acid, oleic acid, ricinoleic acid, vaccenic acid, linoleic acid, crepenynic acid, dehydrocrepenynic acid, linolenic acid (Linolenic acid), Stearidonic acid, Sterculic acid, Gadoleic acid, Dihomo-γ-Linolenic acid (DHLA), Eicosatetraenoic acid, Arachidone Arachidonic acid, Eicosapentaenoic acid (EPA), Erucic acid, Chicoric acid, Docosapentaenoic acid (DPA), Docosahexaenoic acid (Docosahexaenoic acid, DHA), and nervonic acid Will at least one member selected from,
    상기 포화지방산의 에스테르 화합물은 부티르산 에틸 에스테르(Butyric acid ethyl ester), 카프로산 에틸 에스테르(Caproic acid ethyl ester), 카프릴산 에틸 에스테르(Caprylic acid ethyl ester), 카프르산 에틸 에스테르(Capric acid ethyl ester), 라우르산 에틸 에스테르(Lauric acid ethyl ester), 미리스트산 에틸 에스테르(Myristic acid ethyl ester), 테트라메틸데카노산 에틸 에스테르(Tetramethyl decanoic acid ethyl ester), 디하이드로스테르쿨린산 에틸 에스테르(Dihydrosterculic acid ethyl ester), 튜베르큘로스테아린산 에틸 에스테르(Tuberculostearic acid ethyl ester), 아라키드산 에틸 에스테르(Arachidic acid ethyl ester), 베헨산 에틸 에스테르(Behenic acid ethyl ester), 리그노세르산 에틸 에스테르(Lignoceric acid ethyl ester), 세로트산 에틸 에스테르(Cerotic acid ethyl ester), 몬타닌산 에틸 에스테르(Montanic acid ethyl ester), 멜리스산 에틸 에스테르(Melissic acid ethyl ester), 및 코리노미콜산 에틸 에스테르(Corynomycolic acid ethyl ester)로 이루어진 군으로부터 선택되는 1종 이상의 것이며,The ester compound of saturated fatty acid is butyric acid ethyl ester, caproic acid ethyl ester, caprylic acid ethyl ester, capric acid ethyl ester ), Lauric acid ethyl ester, myristic acid ethyl ester, tetramethyl decanoic acid ethyl ester, dihydrosterculic acid ethyl ester acid ethyl ester, Tuberculostearic acid ethyl ester, Arachidic acid ethyl ester, Behenic acid ethyl ester, Lignoceric acid ethyl ester, cerotic acid ethyl ester, montanic acid ethyl ester, meli Acid ethyl ester (Melissic acid ethyl ester), and Corey nominal cholic acid ethyl ester will be at least one selected from the group consisting of (Corynomycolic acid ethyl ester),
    상기 불포화 지방산의 에스테르 화합물은 데카-2-엔-4,6,8-트리이노산 에틸 에스테르((E)-deca-2-en-4,6,8-triynoic acid ethyl ester), 운데세노산 에틸 에스테르(Undecenoic acid ethyl ester), 히드노카르프산 에틸 에스테르(Hydnocarpic acid ethyl ester), 팔미톨레산 에틸 에스테르(Palmitoleic acid ethyl ester), 차울무그르산 에틸 에스테르(Chaulmoogric acid ethyl ester), 말발산 에틸 에스테르(Malvalic acid ethyl ester), 올레산 에틸 에스테르(Oleic acid ethyl ester), 리시놀레산 에틸 에스테르(Ricinoleic acid ethyl ester), 박센산 에틸 에스테르(Vaccenic acid ethyl ester), 리놀레산 에틸 에스테르(Linoleic acid ethyl ester), 크레페닌산 에틸 에스테르(Crepenynic acid ethyl ester), 디하이드로크레페닌산 에틸 에스테르(Dehydrocrepenynic acid ethyl ester), 스테아리돈산 에틸 에스테르(Stearidonic acid ethyl ester), 스테르쿨린산 에틸 에스테르(Sterculic acid ethyl ester), 가돌레산 에틸 에스테르(Gadoleic acid ethyl ester), 에이코사테트라에노산 에틸 에스테르(Eicosatetraenoic acid ethyl ester), 아라키돈산 에틸 에스테르(Arachidonic acid ethyl ester), 에이코사펜타에노산 에틸 에스테르(Eicosapentaenoic acid ethyl ester), 에루스산 에틸 에스테르(Erucic acid ethyl ester), 치코르산 에틸 에스테르(Cichoric acid ethyl ester), 도코사펜타에노산 에틸 에스테르(Docosapentaenoic acid ethyl ester), 도코사헥사에노산 에틸 에스테르(Docosahexaenoic acid ethyl ester), 및 네르본산 에틸 에스테르(Nervonic acid ethyl ester)로 이루어진 군으로부터 선택되는 1종 이상인 것을 특징으로 하는 위벽 보호용 조성물.The ester compound of the unsaturated fatty acid is deca-2-ene-4,6,8-triinoic acid ethyl ester ((E) -deca-2-en-4,6,8-triynoic acid ethyl ester), ethyl undecenoic acid Undecenoic acid ethyl ester, Hydnocarpic acid ethyl ester, Palmitoleic acid ethyl ester, Chaulmoogric acid ethyl ester, Malvalic acid ethyl ester (Malvalic acid ethyl ester), oleic acid ethyl ester, ricinoleic acid ethyl ester, vaccenic acid ethyl ester, linoleic acid ethyl ester, Crepenynic acid ethyl ester, Dehydrocrepenynic acid ethyl ester, Stearidonic acid ethyl ester, Steculinic acid ethyl ester rculic acid ethyl ester, gadoleic acid ethyl ester, eicosatetraenoic acid ethyl ester, arachidonic acid ethyl ester, eicosapentaenoic acid ethyl ester Eicosapentaenoic acid ethyl ester, Erucic acid ethyl ester, Chicoric acid ethyl ester, Docosapentaenoic acid ethyl ester, Docosahexaenoic acid ethyl ester (Docosahexaenoic acid ethyl ester), and Nervonic acid ethyl ester (Nervonic acid ethyl ester) is a composition for protecting the stomach wall, characterized in that at least one member.
  12. 올레산, 리놀레산, 디하이드로크레페닌산, 도코사헥사에노산, 아라키돈산, 올레산 에틸 에스테르, 리놀레산 에틸 에스테르, 디하이드로크레페닌산 에틸 에스테르, 도코사헥사에노산 에틸 에스테르 및 아라키돈산 에틸 에스테르로 이루어진 군으로부터 선택되는 1종 이상, 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 위벽 보호용 조성물.Selected from the group consisting of oleic acid, linoleic acid, dihydrocrefenic acid, docosahexaenoic acid, arachidonic acid, oleic acid ethyl ester, linoleic acid ethyl ester, dihydrocrefeninic acid ethyl ester, docosahexaenoic acid ethyl ester and arachidonic acid ethyl ester 1 or more, or a composition for protecting the stomach wall containing a pharmaceutically acceptable salt thereof as an active ingredient.
  13. 리놀레산, 리놀레산 에스테르 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 함유하는 위벽 보호용 조성물.Linoleic acid, linoleic acid esters or pharmaceutically acceptable salts thereof as an active ingredient for gastric wall protective composition.
  14. 탄소수 3 내지 40개의 포화 지방산, 상기 포화지방산의 메틸 또는 에틸 에스테르 화합물, 탄소수 8 내지 30개의 불포화 지방산 및 상기 불포화 지방산의 메틸 또는 에틸 에스테르 화합물로 이루어진 군에서 선택된 1종 이상의 화합물, 또는 이의 약학적으로 허용 가능한 염(제1 성분), 및At least one compound selected from the group consisting of saturated fatty acids having 3 to 40 carbon atoms, methyl or ethyl ester compounds of the saturated fatty acids, unsaturated fatty acids having 8 to 30 carbon atoms and methyl or ethyl ester compounds of the unsaturated fatty acids, or pharmaceutically thereof Acceptable salts (first component), and
    H2 수용체 길항제, 프로톤 펌프 저해제, 가스트린 수용체 저해제, 위점막 보호제 및 인진쑥 배지에서 배양된 노루궁뎅이 버섯 균사체(Hericium erinaceum Hypha Cultivated with Artemisia capillaries, HEAC) 추출물로 이루어진 군에서 선택된 1종 이상(제2 성분)을 유효성분으로 함유하는 위벽 보호용 조성물.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) ) Composition for protecting the stomach wall containing as an active ingredient.
  15. 제14항에 있어서,The method of claim 14,
    상기 포화 지방산은 부티르산(Butyric acid), 카프로산(Caproic acid), 카프릴산(Caprylic acid), 카프르산(Capric acid), 라우르산(Lauric acid), 미리스트산(Myristic acid), 테트라메틸데카노산(Tetramethyldecanoic acid), 팔미트산(Palmitic acid), 스테아르산(Stearic acid), 디하이드로스테르쿨린산(Dihydrosterculic acid), 튜베르큘로스테아르산(Tuberculostearic acid), 아라키드산(Arachidic acid), 베헨산(Behenic acid), 리그노세르산(Lignoceric acid), 세로트산(Cerotic acid), 몬타닌산(Montanic acid), 멜리스산(Melissic acid), 및 코리노미콜산(Corynomycolic acid)로 이루어진 군에서 선택된 1종 이상의 것이고,The saturated fatty acid is butyric acid, caproic acid, caprylic acid, caprylic acid, capric acid, lauric acid, myristic acid, tetra Tetramethyldecanoic acid, Palmitic acid, Stearic acid, Dihydrosterculic acid, Tuberculostearic acid, Arachidic acid acid, Behenic acid, Lignoceric acid, Cerotic acid, Montanic acid, Melissic acid, and Corinomycolic acid At least one selected from the group,
    상기 불포화 지방산은 디하이드로메트리카리아산(Dehydromatricaria acid), 운데세노산(Undecenoic acid), 히드노카르프산(Hydnocarpic acid), 팔미톨레산(Palmitoleic acid), 차울무그르산(Chaulmoogric acid), 말발산(Malvalic acid), 올레산(Oleic acid), 리시놀레산(Ricinoleic acid), 박센산(Vaccenic acid), 리놀레산(Linoleic acid), 크레페닌산(Crepenynic acid), 디하이드로크레페닌산(Dehydrocrepenynic acid), 리놀렌산(Linolenic acid), 스테아리돈산(Stearidonic acid), 스테르쿨린산(Sterculic acid), 가돌레산(Gadoleic acid), DHLA (Dihomo-γ-Linolenic acid), 에이코사테트라에노산(Eicosatetraenoic acid), 아라키돈산(Arachidonic acid), 에이코사펜타에노산(Eicosapentaenoic acid, EPA), 에루스산(Erucic acid), 치코르산(Cichoric acid), 도코사펜타에노산(Docosapentaenoic acid, DPA), 도코사헥사에노산(Docosahexaenoic acid, DHA), 및 네르본산(Nervonic acid)으로 이루어진 군에서 선택된 1종 이상의 것이고,The unsaturated fatty acid is dehydromatricaria acid (Dehydromatricaria acid), Undecenoic acid (Undecenoic acid), Hydnocarpic acid (Hydnocarpic acid), Palmitoleic acid (Palmitoleic acid), Chaulmoogric acid (Chaulmoogric acid), Mal Malvalic acid, oleic acid, ricinoleic acid, vaccenic acid, linoleic acid, crepenynic acid, dehydrocrepenynic acid, linolenic acid (Linolenic acid), Stearidonic acid, Sterculic acid, Gadoleic acid, DHLA (Dihomo-γ-Linolenic acid), Eicosatetraenoic acid, Arachidone Arachidonic acid, Eicosapentaenoic acid (EPA), Erucic acid, Chicoric acid, Docosapentaenoic acid (DPA), Docosahexaenoic acid (Docosahexaenoic acid, DHA), and nervonic acid These will stand more than one kind,
    상기 포화지방산의 에스테르 화합물은 부티르산 에틸 에스테르(Butyric acid ethyl ester), 카프로산 에틸 에스테르(Caproic acid ethyl ester), 카프릴산 에틸 에스테르(Caprylic acid ethyl ester), 카프르산 에틸 에스테르(Capric acid ethyl ester), 라우르산 에틸 에스테르(Lauric acid ethyl ester), 미리스트산 에틸 에스테르(Myristic acid ethyl ester), 테트라메틸데카노산 에틸 에스테르(Tetramethyl decanoic acid ethyl ester), 팔미트산 에틸 에스테르(Palmitic acid ethyl ester), 스테아르산 에틸 에스테르(Stearic acid ethyl ester), 디하이드로스테르쿨린산 에틸 에스테르(Dihydrosterculic acid ethyl ester), 튜베르큘로스테아린산 에틸 에스테르(Tuberculostearic acid ethyl ester), 아라키드산 에틸 에스테르(Arachidic acid ethyl ester), 베헨산 에틸 에스테르(Behenic acid ethyl ester), 리그노세르산 에틸 에스테르(Lignoceric acid ethyl ester), 세로트산 에틸 에스테르(Cerotic acid ethyl ester), 몬타닌산 에틸 에스테르(Montanic acid ethyl ester), 멜리스산 에틸 에스테르(Melissic acid ethyl ester), 및 코리노미콜산 에틸 에스테르(Corynomycolic acid ethyl ester)로 이루어진 군에서 선택된 것이고,The ester compound of saturated fatty acid is butyric acid ethyl ester, caproic acid ethyl ester, caprylic acid ethyl ester, capric acid ethyl ester ), Lauric acid ethyl ester, myristic acid ethyl ester, tetramethyl decanoic acid ethyl ester, palmitic acid ethyl ester ), Stearic acid ethyl ester, dihydrosterculic acid ethyl ester, tuberculostearic acid ethyl ester, arachidic acid ester ethyl ester, Behenic acid ethyl ester, Lignoceric acid ethyl ester, It is selected from the group consisting of cerotic acid ethyl ester, montanic acid ethyl ester, melissic acid ethyl ester, and corynomycolic acid ethyl ester. ,
    상기 불포화 지방산의 에스테르 화합물은 데카-2-엔-4,6,8-트리이노산 에틸 에스테르((E)-deca-2-en-4,6,8-triynoic acid ethyl ester), 운데세노산 에틸 에스테르(Undecenoic acid ethyl ester), 히드노카르프산 에틸 에스테르(Hydnocarpic acid ethyl ester), 팔미톨레산 에틸 에스테르(Palmitoleic acid ethyl ester), 차울무그르산 에틸 에스테르(Chaulmoogric acid ethyl ester), 말발산 에틸 에스테르(Malvalic acid ethyl ester), 올레산 에틸 에스테르(Oleic acid ethyl ester), 리시놀레산 에틸 에스테르(Ricinoleic acid ethyl ester), 박센산 에틸 에스테르(Vaccenic acid ethyl ester), 리놀레산 에틸 에스테르(Linoleic acid ethyl ester), 크레페닌산 에틸 에스테르(Crepenynic acid ethyl ester), 디하이드로크레페닌산 에틸 에스테르(Dehydrocrepenynic acid ethyl ester), 리놀렌산 에틸 에스테르(Linolenic acid ethyl ester), 스테아리돈산 에틸 에스테르(Stearidonic acid ethyl ester), 스테르쿨린산 에틸 에스테르(Sterculic acid ethyl ester), 가돌레산 에틸 에스테르(Gadoleic acid ethyl ester), 에이코사테트라에노산 에틸 에스테르(Eicosatetraenoic acid ethyl ester), 아라키돈산 에틸 에스테르(Arachidonic acid ethyl ester), 에이코사펜타에노산 에틸 에스테르(Eicosapentaenoic acid ethyl ester), 에루스산 에틸 에스테르(Erucic acid ethyl ester), 치코르산 에틸 에스테르(Cichoric acid ethyl ester), 도코사펜타에노산 에틸 에스테르(Docosapentaenoic acid ethyl ester), 도코사헥사에노산 에틸 에스테르(Docosahexaenoic acid ethyl ester), 및 네르본산 에틸 에스테르(Nervonic acid ethyl ester)로 이루어진 군에서 선택된 1종 이상인 것을 특징으로 하는 위벽 보호용 조성물.The ester compound of the unsaturated fatty acid is deca-2-ene-4,6,8-triinoic acid ethyl ester ((E) -deca-2-en-4,6,8-triynoic acid ethyl ester), ethyl undecenoic acid Undecenoic acid ethyl ester, Hydnocarpic acid ethyl ester, Palmitoleic acid ethyl ester, Chaulmoogric acid ethyl ester, Malvalic acid ethyl ester (Malvalic acid ethyl ester), oleic acid ethyl ester, ricinoleic acid ethyl ester, vaccenic acid ethyl ester, linoleic acid ethyl ester, Crepenynic acid ethyl ester, dehydrocrepenynic acid ethyl ester, linolenic acid ethyl ester, stearic acid ethyl ester acid ethyl ester, Sterculic acid ethyl ester, Gadoleic acid ethyl ester, Eicosatetraenoic acid ethyl ester, Arachidonic acid ethyl ester ethyl ester, Eicosapentaenoic acid ethyl ester, Erucic acid ethyl ester, Chicoric acid ethyl ester, Docosapentaenoic acid ethyl ester (Docosapentaenoic acid ethyl ester), docosahexaenoic acid ethyl ester (Docosahexaenoic acid ethyl ester), and ervonic acid ethyl ester (Nervonic acid ethyl ester), characterized in that at least one member selected from the group consisting of.
  16. 제14항에 있어서, 상기 제1 성분은 리놀레산, 리놀레산 에스테르 또는 이들의 약학적으로 허용가능한 염인 것을 특징으로 하는 위벽 보호용 조성물.15. The composition of claim 14, wherein the first component is linoleic acid, linoleic acid ester, or a pharmaceutically acceptable salt thereof.
  17. 제14항에 있어서,The method of claim 14,
    상기 H2 수용체 길항제는 시메티딘, 라니티딘, 파모티딘, 록사티딘, 니자티딘, 및 이들의 약학적으로 허용 가능한 염, 이성질체 및 이성질체의 염으로 이루어진 군에서 선택된 1종 이상의 것이고,The H 2 receptor antagonist is at least one selected from the group consisting of cimetidine, ranitidine, pamotidine, roxatidine, nizatidine, and salts of pharmaceutically acceptable salts, isomers and isomers thereof,
    상기 프로톤 펌프 저해제는 오메프라졸, 란소프라졸, 판토프라졸, 라베프라졸, 레바프라잔, 일라프라졸, 파리프라졸, 레미노프라졸, 및 이들의 약학적으로 허용 가능한 염, 이들의 거울상이성질체, 및 상기 거울상이성질체의 약학적으로 허용 가능한 염으로 이루어진 군에서 선택된 1종 이상의 것이고,The proton pump inhibitors are omeprazole, lansoprazole, pantoprazole, labeprazole, revaprazan, ilaprazole, parrazole, reminoprazole, and pharmaceutically acceptable salts thereof, enantiomers thereof, and the enantiomer At least one member selected from the group consisting of pharmaceutically acceptable salts of isomers,
    상기 가스트린 수용체 저해제는 레바미피드 및 이의 약학적으로 허용 가능한 염으로 이루어진 군에서 선택된 1종 이상의 것이고,The gastrin receptor inhibitor is at least one selected from the group consisting of levamifeed and its pharmaceutically acceptable salts,
    상기 위점막 보호제는 미소프로스톨, 이의 약학적으로 허용 가능한 염, 및 애엽(Artemisiae Argyi Folium) 추출물로 이루어진 군에서 선택된 1종 이상의 것이며,The gastric mucosa protective agent is at least one selected from the group consisting of misoprostol, a pharmaceutically acceptable salt thereof, and Artemisiae Argyi Folium extract,
    상기 인진쑥 배지에서 배양된 노루궁뎅이 버섯 균사체(Hericium erinaceum Hypha Cultivated with Artemisia capillaries, HEAC) 추출물은 인진쑥 배지에서 배양된 노루궁뎅이 버섯 균사체를 물, 탄소수 1 내지 5의 알코올(25 내지 100 v/v%), 헥산, 클로로포름, 염화메틸렌, 아세토니트릴, 아세톤 및 에틸아세테이트로 이루어진 군에서 선택된 1종 이상의 용매로 추출하여 얻어진 것이거나, 상기 얻어진 추출물에 탄소수 1 내지 5의 알코올(25 내지 100 v/v%), 헥산, 염화메틸렌, 및 에틸아세테이트로 이루어진 군에서 선택된 1종 이상을 추가로 가하여 얻어지는 것임을 특징으로 하는 위벽 보호용 조성물.Helicium erinaceum Hypha Cultivated with Artemisia capillaries (HEAC) extracts cultured in the Artemisia agar medium are water, alcohols having 1 to 5 carbon atoms (25 to 100 v / v%). , Obtained by extraction with one or more solvents selected from the group consisting of hexane, chloroform, methylene chloride, acetonitrile, acetone and ethyl acetate, or an alcohol having 1 to 5 carbon atoms (25 to 100 v / v%) , Hexane, methylene chloride, and ethyl acetate, the composition for protecting the stomach wall, characterized in that obtained by further adding one or more selected from the group consisting of.
  18. 제14항에 있어서, 상기 제1 성분과 제2 성분은 하나의 제형으로 제제화되어 한번에 투여되는 형태이거나, 각각 제제화되어 별도로 투여되는 형태인 것을 특징으로 하는 위벽 보호용 조성물.The composition for protecting the stomach wall according to claim 14, wherein the first component and the second component are formulated into one formulation and administered at one time, or each formulation and separately administered.
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