WO2014208799A1 - Composition pour la prévention ou le traitement de la stéatose hépatique comprenant un extrait d'evodiae fructus et un composé alcaloïde isolé à partir de celui-ci comme ingrédients actifs - Google Patents

Composition pour la prévention ou le traitement de la stéatose hépatique comprenant un extrait d'evodiae fructus et un composé alcaloïde isolé à partir de celui-ci comme ingrédients actifs Download PDF

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WO2014208799A1
WO2014208799A1 PCT/KR2013/005748 KR2013005748W WO2014208799A1 WO 2014208799 A1 WO2014208799 A1 WO 2014208799A1 KR 2013005748 W KR2013005748 W KR 2013005748W WO 2014208799 A1 WO2014208799 A1 WO 2014208799A1
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fatty liver
preventing
sewage
composition
extract
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PCT/KR2013/005748
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English (en)
Korean (ko)
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이기업
오원근
고은희
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재단법인 아산사회복지재단
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Priority to PCT/KR2013/005748 priority Critical patent/WO2014208799A1/fr
Publication of WO2014208799A1 publication Critical patent/WO2014208799A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/754—Evodia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • 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
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics

Definitions

  • the present invention relates to a composition for preventing or treating fatty liver containing Evodia rutaecarpa extract and an alkaloid compound isolated therefrom as an active ingredient.
  • Non-alcoholic fatty liver disease is a disease that has no history of alcohol consumption, but has similar tissue findings as alcoholic fatty liver. Obesity is known as the most important cause.
  • the most important mechanism of the development of non-alcoholic fatty liver disease is insulin resistance, which is considered to be a common etiology of metabolic syndrome such as diabetes, obesity and hyperlipidemia.
  • Each disease belonging to the metabolic syndrome may be correlated or independently affect the progression, severity and complications of NAFLD.
  • NAFLDs come in the form of nonalcoholic steatohepatitis (NASH), which is accompanied by the destruction of hepatocytes, and some progress to liver cirrhosis or liver cancer through liver fibrosis.
  • NASH nonalcoholic steatohepatitis
  • Fatty liver disease caused by metabolic syndrome (1) increases the amount of free fatty acids from adipocytes into the liver, resulting in fat accumulation, and (2) an important role in the biosynthesis of triglycerides due to hyperglycemia and hyperinsulinemia. It is known to activate SREBP-1c, a transcription factor that causes fat accumulation in liver tissue. Recently, it has been reported that metformin and PPAR-ligand, which activate AMP-activated protein kinase (AMPK), which are involved in cellular energy metabolism, can prevent the development of fatty liver by inhibiting SREBP-1c activity. It's controversial. In addition, there are no reports of drugs that can efficiently regulate SREBP-1c other than metformin and PPAR-ligand.
  • AMPK AMP-activated protein kinase
  • Evodia rutaecarpa is a deciduous shrub that grows in the southern part of Korea. In oriental medicine, it is called sewage or sewage oil which is obtained by picking green and brown immature fruit around September. It is used for dry, dry, detoxification and diuretic. Sewage extract has been reported to have analgesic activity in experimental animals and is known to increase blood flow improvement. Other efficacies in filthy feeding are known to be effective in treating abdominal pain, headache pain, diarrhea, allodynia and hypertension, and are known to be effective in removing rashes and eczema caused by the skin on the head. Patents and documents related to such sewage oil "whitening cosmetic composition containing sewage oil extract (Korean Patent No.
  • the present inventors searched about 1500 kinds of natural products to develop new non-alcoholic fatty liver preventive or therapeutic substances with low toxicity from natural products, and separated five kinds of alkaloid compounds as active substances from sewage extract.
  • the present invention was completed by confirming that the isolated compound has a prophylactic or therapeutic effect on non-alcoholic fatty liver.
  • Another object of the present invention to provide a food composition for preventing or improving fatty liver comprising sewage oil extract and alkaloid compound isolated therefrom as an active ingredient.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of fatty liver comprising sewage oil extract and alkaloid compounds isolated therefrom as an active ingredient.
  • the present invention provides a food composition for preventing or improving fatty liver comprising a sewage oil extract and an alkaloid compound separated therefrom as an active ingredient.
  • the present invention relates to a composition for the prevention or treatment of fatty liver, comprising sesame oil extract and alkaloid compounds isolated therefrom as an active ingredient.
  • the sewage extract of the present invention and the alkaloid compound isolated therefrom have in vivo stability, increase the activity of ANT1 enzyme, promote fatty acidization in liver tissue of fatty liver animal model and thereby produce fat accumulation and triglyceride By effectively inhibiting, it can be usefully used for the prevention or treatment of fatty liver, especially non-alcoholic fatty liver.
  • 1 is a diagram showing the HPLC analysis spectrum of the sewage ethanol extract.
  • Figure 2 is a diagram showing the ANT1 activity of alkaloid compounds isolated from the sesame oil extract.
  • Figure 3 is a diagram showing the effect of inhibiting fat accumulation in liver tissue of the evodiamine of db / db mice.
  • Figure 4 is a diagram showing the effect of triglycerides in the liver tissue of the evodiamine of db / db mice.
  • Fig. 5 is a diagram showing the effect of inhibiting fat accumulation in liver tissue of evodiamine in a fatty liver animal model by LXR antagonist.
  • FIG. 6 is a diagram showing the effect of inhibiting triglyceride production in the liver tissue of the evodiamine of a fatty liver animal model by LXR antagonist.
  • FIG. 7 is a diagram showing the effect of evodiamine on fatty acid oxidation inhibitory action by LXR antagonist treatment.
  • the present invention provides a composition for the prevention or treatment of fatty liver, comprising sesame oil extract and alkaloid compounds isolated therefrom as an active ingredient.
  • the composition comprises a pharmaceutical composition or a food composition.
  • Fructus extract of the present invention can be obtained by the following method. Sewage oil is washed with water to remove debris, dried in the shade and crushed. Sewage oil can be used without limitation, cultivated or commercially available. Appropriate amount of solvent is added to the ground sewage oil powder to allow complete immersion to obtain the sewage oil extract.
  • the extraction method can be impregnated or warmed at room temperature.
  • the extraction solvent is not limited thereto, but may be one or more solvents selected from water, alcohols having 1 to 4 carbon atoms, and mixed solvents thereof, preferably methanol or ethanol, and more preferably ethanol.
  • the sewage oil extract concentrate was suspended in distilled water and fractionated sequentially with hexane, ethyl acetate, butanol and water to obtain a fraction.
  • the ethyl acetate fraction of the fraction showed the best ANT1 activity.
  • the active material was separated from the sewage oil ethyl acetate fraction having the highest ANT1 activity using liquid chromatography, and the active material showed the best ANT1 activity among the alkaloid compounds.
  • the alkaloid compound includes evodiamine, evodiamine, rutaecarpine, 7-hydroxyrutaecarpine, norketoyobyrine, and ketoyobyrine. .
  • the alkaloid compound isolated from the sewage oil extract may be obtained by the following method. Specifically, a known method used for isolation and extraction of plant components, such as extraction with an organic solvent alcohol (methanol, ethanol, propanol, etc.) or a water-soluble alcohol, a distribution of an organic solvent and water, a method by column chromatography, or the like alone or suitably Can be easily obtained.
  • an organic solvent alcohol methanol, ethanol, propanol, etc.
  • a water-soluble alcohol a distribution of an organic solvent and water
  • a method by column chromatography, or the like alone or suitably Can be easily obtained.
  • the chromatography used in the present invention is not limited thereto, but silica gel column chromatography, LH-20 column chromatography, thin layer chromatography, or high performance High performance liqid chromatography and the like can be used.
  • sesame oil extract and alkaloid compounds isolated therefrom increase the activity of ANT1 enzyme, promote fatty acidization in liver tissue of fatty liver animal model and thereby effectively inhibit fat accumulation and production of triglycerides.
  • sewage oil extract and alkaloid compound isolated therefrom according to the present invention can be used as a medicine or health functional food useful for the prevention or treatment of fatty liver, especially non-alcoholic fatty liver.
  • composition of the present invention may be used alone or in the form of a combination or aggregate with other pharmaceutically active compounds.
  • the sewage oil extract which is an active ingredient of the composition of the present invention, and the alkaloid-based compound isolated therefrom may be administered in combination with other known preventive or therapeutic drugs for fatty liver.
  • composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention or treatment of fatty liver.
  • composition of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions. It may also be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like in the form of conventional formulations, external preparations, suppositories, and sterile injectable solutions. Suitable formulations known in the art are preferably those disclosed in Remington's Pharmaceutical Science, recently, Mack Publishing Company, Easton PA.
  • Carriers, excipients and diluents that may be included 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, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate and mineral oil.
  • diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations include at least one excipient such as starch, calcium carbonate, sucrose, lactose, It is prepared by mixing gelatin.
  • excipients such as starch, calcium carbonate, sucrose, lactose, It is prepared by mixing gelatin.
  • lubricants such as magnesium stearate and talc are also used.
  • Oral liquid preparations include suspensions, solvents, 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.
  • 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.
  • base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • the dosage of the sewage extract of the present invention and the alkaloid compound isolated therefrom depends on the age, sex, and weight of the subject to be treated, the specific disease or pathology to be treated, the severity of the disease or pathology, the route of administration, and the judgment of the prescriber. It may vary. Dosage determination based on these factors is within the level of skill in the art and generally dosages range from 0.1 mg / kg / day to approximately 1,000 mg / kg / day. More preferred dosage is 1 mg / kg / day to 500 mg / kg / day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
  • the compounds of the present invention can be administered to a subject by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injections. Since the compound of the present invention has little toxicity and side effects, it is a drug that can be used safely even when taken for a long time for the purpose of prevention.
  • the health functional food refers to a food having a bioregulatory function, such as prevention and treatment of disease, biodefence, immunity, recovery of the disease, inhibition of aging, and should be harmless to the human body when taken in the long term.
  • the composition of the present invention may be added to a dietary supplement for the purpose of preventing or improving fatty liver.
  • the composition of the present invention When the composition of the present invention is used as a food additive, the composition may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method.
  • the mixed amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment).
  • the compositions of the present invention are added in an amount of up to 15% by weight, preferably up to 10% by weight relative to the raw materials.
  • the active ingredient may be used in an amount above the above range because there is no problem in terms of safety.
  • Examples of the food to which the substance may be added include meat, sausage, bread, chocolate, candy, snacks, confectionary, pizza, ramen, other noodles, dairy products including gum, ice cream, various soups, beverages, tea, drink, Alcoholic beverages and vitamin complexes, and the like and include all of the health foods in the conventional sense.
  • the health beverage composition of the present invention may include various flavors or natural carbohydrates, and the like as an additional ingredient, as in a general beverage.
  • the natural carbohydrates described above may be used as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and natural sweeteners such as dextrin and cyclodextrin, and synthetic sweeteners such as saccharin and aspartame.
  • the proportion of the natural carbohydrate is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.
  • the composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, And carbonating agents used in the carbonated beverage.
  • the composition of the present invention may include a pulp for the production of natural fruit juice, fruit juice drinks and vegetable drinks. These components can be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
  • ANT1 is a carrier protein present in the inner membrane of mitochondria and plays a role (ATP / ADP translocator) to export ATP produced during oxidative phosphorylation of mitochondria into the cytoplasm. Previous studies have shown that mitochondrial protein ANT1 may be an important pathological mechanism for fatty liver prevention. Therefore, in the present invention, in order to search for candidates for the treatment of fatty liver, substances that regulate the activity of ANT1 were searched.
  • Reverse phase (RP-18) column chromatography was performed again under the conditions of increasing the fraction 5 from 2: 1 to 5: 1 using MeOH-H 2 O mixed solvent to obtain five smaller fractions (fr 5.1-5.5).
  • Example 1 The structure of five compounds isolated from the sewage oil extract obtained in Example 1 was analyzed.
  • the chemical structure of the compound was measured using an ESI mass spectrometer (Electrospray Ionization mass spectrometer) to determine the molecular weight, and the chemical structure was confirmed by 1 H and 13 C-NMR analysis.
  • ESI mass spectrometer Electrospray Ionization mass spectrometer
  • Example 1 In order to confirm the feasibility of the sewage oil extract prepared in Example 1 and the compounds 1-5 isolated therefrom as a therapeutic agent for fatty liver, the activity of ANT1 was measured.
  • the activation activity of ANT1 was measured using the ANT1 promoter-luciferase system.
  • the promoter is a sequence that regulates transcription, and the luciferase gene located behind the nucleotide sequence of the promoter increases in expression as the promoter becomes more active. Therefore, the activity of the promoter can be known from the expression level of luciferase.
  • ANT1 is a mitochondrial protein
  • mouse endothelial cell (endothelioma) bEnd.3 cells with relatively high distribution of mitochondria were selected to measure promoter activity.
  • bEnd.3 cells were collected by treatment with 0.25% trypsin, and then the supernatant was removed and suspended in DMEM medium without bovine serum.
  • lipofectamine lipofectamine (lipopectAMINE, life Technologies, Inc) was added to 100 ⁇ l of the DMEM, and the mixture was slowly mixed and allowed to stand at room temperature for 15 minutes. Standard to consistently match the efficiency of 50 ng of pANT1 II-Luc or mpANT1-Luc (plasmid with luciferase gene) and 0.1 ⁇ g of pCMV- ⁇ -galactosidase (transfection, how DNA is introduced into animal cells) Plasmid with ⁇ -galactosidase gene], 0.1 ⁇ g of ANT1 expression vector, or a microprecision tube containing a vector to be used as a control. It was left for another 15 minutes.
  • the mixture of lipofectamine and DNA-plasmid and b-End.3 cells were slowly mixed and incubated at room temperature for 20 minutes in suspension, then aliquoted in a 60 mm culture vessel and incubated in a CO 2 incubator for 24 hours. The next day, 10 ⁇ g / ml of each of the sewage extracts prepared in Example 1 and 1 ⁇ g / ml of each of the compounds separated therefrom were added thereto, followed by further incubation for 24 hours.
  • bEnd.3 cells were washed twice with PBS, 500 ⁇ l of extract solution was added to each culture vessel, and the cells were disrupted and centrifuged at 14,000 rpm for 5 minutes.
  • Luciferase activity was obtained by supernatant extracted from 100 ⁇ l of cells, 100 ⁇ l of 20 nM D-luciferin (substrate luminescent using luciferase) and 300 ⁇ l of reaction solution (20 mM glycylglycin, 12.5 mM MgSO 4, 3 mM EGTA, 15 mM potassium). phosphate, 1 mM DTT, 1 mM ATP) and measured with a photometer (luminometor, Berthold Clinolumat).
  • luciferase activity was corrected by measuring the activity of ⁇ -galactosidase.
  • the activity of ⁇ -galactosidase was 30 ⁇ l of cell extract, 66 ⁇ l of o-nitrophenyl- ⁇ -D-galactoside (4 mg / ml), and 204 ⁇ l of reaction solution (0.1 M sodium phosphate, 1 mM MgCl 2 , 45 mM ⁇ ).
  • -mercaptoethanol pH 7.5
  • absorbance was measured with a spectrophotometer.
  • Table 1 and FIG. 2 The results of confirming the activity of ANT1 of the sesame oil extract and alkaloid compounds 1-5 separated therefrom are shown in Table 1 and FIG. 2, respectively.
  • mice Twenty ICR mouse strains, which are common mice, were used, and 10 rats were assigned to the control group and 10 rats to the experimental group.
  • the control group was orally administered with only a solvent containing no compound (PEG-400 / tween-80 / EtOH, 8/1/1, v / v / v), and the experimental group was 2.0 g / kg of evodiamine separated from the sesame oil extract. It was administered orally at the concentration.
  • Each mortality was examined 24 hours after administration, and both the control group and the experimental group administered with 2.0g / kg evodiamine survived. It was confirmed that the evodiamine did not show acute toxicity at the concentration of 2.0g / kg.
  • OLETF rats were used as experimental animals, and only control solvent was administered orally with evodiamine at a concentration of 200 mg / kg.
  • blood was collected from the animals, and blood concentrations of GOT (glutamate-oxalate-transferase), GPT (glutamate-pyruvate-transferase), creatine kinase and creatinine were measured.
  • GOT glutamate-oxalate-transferase
  • GPT glutapyruvate-transferase
  • creatine kinase and creatinine were measured.
  • the experimental group of evodiamine did not show any difference between GOT and GPT, which are known to be related to hepatotoxicity, creatinine, which is an indicator of kidney toxicity, and creatine kinase, which is an indicator of muscle toxicity.
  • mice are well known as obese and type 2 diabetic animal models, nonalcoholic fatty liver is also well developed and thus used as animal models.
  • Normal 8-week-old mice (lean) were used as a normal group, and water or evodiamine (Compound 1, 200 mg / kg) was orally administered to 8-week-old db / db mice (control group) for 3 weeks.
  • liver tissue of each group of mice was separated and observed, and the results are shown in FIGS. 3 and 4.
  • the evodiamine isolated from the sewage extract has a prophylactic or therapeutic effect of fatty liver in db / db animal model.
  • LXR Liver X receptor
  • SREBP1c sterol regulatory factor-binding protein 1c
  • mice of 8-week-old C57BL / 6J were orally administered with water or evodiamine 200 mg / kg for 1 week, with oral administration of 50 mg / kg of LXR agonist.
  • the liver tissues of the mice in each group were separated and the triglyceride content in the tissues was measured.
  • Figs. 5 and 6 The inhibitory effect of evodiamine on fat accumulation and neutral fat production in liver tissues of LXR antagonists in liver tissues are shown in Figs. 5 and 6, respectively, and the effects of evodiamine on fatty acid oxidation inhibition by LXR antagonist treatment. The influence is shown in FIG. 7.
  • the evodiamine isolated from the sesame oil extract has a fatty liver prevention and treatment effect in the animal model inducing fatty liver by treatment with LXR antagonist.
  • the sewage oil extract and the alkaloid-based compound separated therefrom were mixed with lactose, potato starch and colloidal silicic acid, 10% gelatin solution was added, and then ground and passed through a mesh body. After drying, the mixture obtained by adding potato starch, syrup and magnesium stearate was made into a tablet.
  • the above composition ratio was dissolved in distilled water to make 100 ml.
  • the solution was bottled and sterilized by heating at 20 ° C. for 30 minutes.
  • the above ingredients are mixed and filled in an airtight cloth to prepare a powder.
  • the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
  • each component is added to the purified water to dissolve it, the lemon flavor is appropriately added, the above components are mixed, purified water is added, the whole is purified to 100 ml, and then filled in a brown bottle.
  • the solution is prepared by sterilization.
  • Sewage oil extract and alkaloid-based compounds separated therefrom were prepared for health promotion cooking seasoning at 0.2 to 10 parts by weight, respectively.
  • Sewage oil extract and alkaloid-based compounds separated therefrom were added to the flour at 0.1 to 5.0 parts by weight, respectively, and bread, cake, cookies, crackers and noodles were prepared using the mixture to prepare foods for health promotion.
  • Sewage oil extract and alkaloid-based compounds separated therefrom were added to the soup and the juice of 0.1 to 1.0 parts by weight, respectively, to prepare meat products for health promotion, soup of noodles and soup.
  • Sewage oil extract and alkaloid-based compounds separated therefrom were added to the milk at 0.1 to 1.0 parts by weight, respectively, to prepare various dairy products such as butter and ice cream.
  • Vitamin B6 0.5 mg
  • composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method.
  • the granules may be prepared and used for preparing a health food composition according to a conventional method.
  • the extract was added to juice to prepare vegetable juice for health promotion.
  • the extract was added to juice to prepare fruit juice for health promotion.
  • the resulting solution is filtered and obtained in a sterilized 2 l container, sealed sterilization and refrigerated and then Used to prepare the healthy beverage composition of the invention.
  • composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

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Abstract

L'invention concerne une composition pour prévenir ou traiter la stéatose hépatique, la composition comprenant un extrait d'Evodiae fructus et un composé alcaloïde isolé à partir de celui-ci comme ingrédients actifs. L'extrait d'Evodiae fructus et le composé alcaloïde isolé à partir de celui-ci de la présente invention sont stables à l'intérieur du corps, augmentent l'activité de l'enzyme ANT1 et activent l'oxydation des lipides dans le tissu hépatique dans un modèle animal de stéatose hépatique et diminuent ainsi efficacement l'accumulation des lipides et la production de triglycérides, et peuvent donc être utilisés avantageusement dans la prévention ou le traitement de la stéatose hépatique et en particulier la stéatose hépatique non alcoolique.
PCT/KR2013/005748 2013-06-28 2013-06-28 Composition pour la prévention ou le traitement de la stéatose hépatique comprenant un extrait d'evodiae fructus et un composé alcaloïde isolé à partir de celui-ci comme ingrédients actifs WO2014208799A1 (fr)

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PCT/KR2013/005748 WO2014208799A1 (fr) 2013-06-28 2013-06-28 Composition pour la prévention ou le traitement de la stéatose hépatique comprenant un extrait d'evodiae fructus et un composé alcaloïde isolé à partir de celui-ci comme ingrédients actifs

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KR20030070232A (ko) * 2002-02-21 2003-08-29 주식회사 바이오젠텍 오수유 추출물을 함유하는 숙취해소 및 항산화 작용을위한 조성물
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113171366A (zh) * 2021-03-30 2021-07-27 安徽医科大学 一种3-（邻三氟甲氧基苯磺酰氨）吴茱萸次碱在制备防治酒精性肝损伤药物中的应用

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