WO2021209070A1 - Composition de ginsénoside présentant une fonction de prévention et de traitement de la stéatose hépatique alcoolique - Google Patents

Composition de ginsénoside présentant une fonction de prévention et de traitement de la stéatose hépatique alcoolique Download PDF

Info

Publication number
WO2021209070A1
WO2021209070A1 PCT/CN2021/088142 CN2021088142W WO2021209070A1 WO 2021209070 A1 WO2021209070 A1 WO 2021209070A1 CN 2021088142 W CN2021088142 W CN 2021088142W WO 2021209070 A1 WO2021209070 A1 WO 2021209070A1
Authority
WO
WIPO (PCT)
Prior art keywords
ginsenoside
pharmaceutical composition
liver
weight
alcoholic fatty
Prior art date
Application number
PCT/CN2021/088142
Other languages
English (en)
Chinese (zh)
Inventor
范代娣
贺婧
段志广
严建亚
Original Assignee
陕西巨子生物技术有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 陕西巨子生物技术有限公司 filed Critical 陕西巨子生物技术有限公司
Priority to AU2021257523A priority Critical patent/AU2021257523B2/en
Publication of WO2021209070A1 publication Critical patent/WO2021209070A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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 invention relates to the field of biomedicine, in particular to a ginsenoside Rk3/Rh4 composition capable of preventing and treating alcoholic fatty liver.
  • Fatty liver disease is a common disease. It can be divided into alcoholic fatty liver (AFL) and non-alcoholic fatty liver (NAFLD) according to the history of heavy drinking.
  • AFL is caused by long-term alcohol consumption.
  • the main causes of injury are toxic metabolites, oxidative stress and metabolic disorders caused by alcohol metabolism in liver cells.
  • the pathogenesis of NAFLD is mainly related to IR, abnormal liver fat metabolism, mitochondrial dysfunction and oxidative stress, genetic variation and metabolic changes, and susceptibility to cell damage.
  • various liver diseases caused by viral hepatitis occupy a major position, with the rise of alcohol in the human diet, the incidence of alcoholic fatty liver is getting higher and higher, and the chance of developing liver cirrhosis and liver cancer far exceeds NAFLD. It has become the second leading cause of liver damage after viral hepatitis.
  • Polyene phosphatidylcholine is a commonly used drug for adjuvant treatment of alcoholic fatty liver. It can effectively reduce oxygen free radicals, protect liver cell membranes, and delay liver fibrosis, thereby promoting the recovery of patients. Almost cause intestinal disorders and cause diarrhea.
  • Ginsenoside is the active ingredient in ginseng and a sterol compound that can affect multiple metabolic pathways in the body. Studies have reported that ginsenosides Rk3 and Rh4 have obvious anti-tumor, anti-oxidant, anti-inflammatory, and anti-apoptosis effects.
  • ginsenosides CK, Rh1 and their combinations can be used to improve non-alcoholic fatty liver
  • alcoholic fatty liver has not been studied
  • ginsenoside Rg1 has a certain effect in the treatment of metabolic disorders caused by drinking, but whether it has a protective effect on the liver has not been studied
  • ginsenoside Rk3/Rh4 Combination drugs have never been used to improve fatty liver, liver disease and the reduction of liver antioxidants caused by alcohol.
  • the purpose of the present invention is to provide a ginsenoside Rk3/Rh4 composition with the function of preventing and treating alcoholic fatty liver.
  • the composition has good therapeutic and improving effects on alcoholic fatty liver.
  • the Rk3/Rh4 composition can significantly improve the survival rate of drinking mice, reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and reduce serum and liver cholesterol (TC) , Triglyceride (TG), low-density lipoprotein (LDL) content, reduce lipid accumulation (oil droplets) in the liver caused by drinking, liver tissue inflammatory infiltration and fatty vacuoles.
  • ALT serum alanine aminotransferase
  • AST aspartate aminotransferase
  • TC serum and liver cholesterol
  • LDL low-density lipoprotein
  • the present invention includes:
  • a pharmaceutical composition that can be used for the prevention and/or treatment of alcoholic fatty liver, which comprises preventive and/or therapeutically effective amounts of ginsenoside Rk3 and ginsenoside Rh4 as active ingredients, and a pharmaceutically acceptable carrier,
  • the weight ratio of ginsenoside Rk3 and ginsenoside Rh4 is 1:0.5-2, preferably 1:0.9-1.1.
  • the weight ratio of ginsenoside Rk3 and ginsenoside Rh4 is 1:1.
  • the pharmaceutical composition according to item 1 based on 100 parts by weight of total ginsenosides contained in the pharmaceutical composition, the total of ginsenoside Rk3 and ginsenoside Rh4 contained in the pharmaceutical composition is 10 parts by weight above.
  • the pharmaceutical composition according to item 1 based on 100 parts by weight of total ginsenosides contained in the pharmaceutical composition, the total of ginsenoside Rk3 and ginsenoside Rh4 contained in the pharmaceutical composition is 100 parts by weight .
  • ginsenoside Rk3 and ginsenoside Rh4 in the preparation of a pharmaceutical composition for the prevention and/or treatment of alcoholic fatty liver, wherein the weight ratio of the ginsenoside Rk3 and ginsenoside Rh4 in the pharmaceutical composition It is 1:0.5-2, preferably 1:0.9-1.1.
  • the ginsenoside Rk3/Rh4 composition for the prevention and treatment of alcoholic fatty liver of the present invention can be either a medicine or any other preparation form; it can be used for the purpose of treating related diseases, or it can be used to improve or prevent drinking caused by alcohol. Fatty liver.
  • the preparation can be ginsenoside Rk3/Rh4, or a compound preparation composed of ginsenoside Rk3/Rh4 and other components, wherein ginsenoside Rk3/Rh4 is the main component.
  • the ginsenoside Rk3/Rh4 of the present invention can be obtained by extraction, transformation and separation of ginseng or American ginseng, or it can be obtained by chemical synthesis. Specifically, the ginsenoside Rk3/Rh4 can be obtained from the roots, stems, and/or leaves of ginseng or American ginseng by extracting, transforming, and isolating them using prior art processes.
  • Rk3 or Rh4 can increase the survival rate of drinking mice, reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and reduce serum and liver
  • ALT serum alanine aminotransferase
  • AST aspartate aminotransferase
  • TC cholesterol
  • TG triglycerides
  • LDL low-density lipoprotein
  • the present invention also includes:
  • ginsenoside Rk3 in the preparation of a pharmaceutical composition for preventing and/or treating alcoholic fatty liver.
  • the ginsenoside Rk3 contained in the pharmaceutical composition is 5 parts by weight or more, preferably 10 parts by weight Parts by weight or more, more preferably 20 parts by weight or more, more preferably 50 parts by weight or more, more preferably 70 parts by weight or more, more preferably 80 parts by weight or more, more preferably 90 parts by weight or more, more preferably 95 parts by weight or more, more preferably 99 parts by weight Above, more preferably 100 parts by weight.
  • ginsenoside Rh4 in the preparation of a pharmaceutical composition for the prevention and/or treatment of alcoholic fatty liver.
  • the ginsenoside Rh4 contained in the pharmaceutical composition is 5 parts by weight or more, preferably 10 parts by weight Parts or more, more preferably 20 parts by weight or more, more preferably 50 parts by weight or more, more preferably 70 parts by weight or more, more preferably 80 parts by weight or more, more preferably 90 parts by weight or more, more preferably 95 parts by weight or more, more preferably 99 parts by weight Above, more preferably 100 parts by weight.
  • the above-mentioned pharmaceutical composition may be, for example, an oral agent or an injection.
  • the oral agent may be, for example, a hard capsule, a soft capsule, a sustained-release capsule, a sugar-coated tablet, a powder, a granule, a tablet, a granule, a dripping pill, a honey pill, a syrup or an oral liquid; the injection is a solution type, mixed Suspension type, emulsion type or lyophilized powder.
  • the above-mentioned pharmaceutical composition may also be an external dosage form, such as an ointment, gel, spray or patch.
  • the above-mentioned pharmaceutical composition may contain excipients or other pharmaceutically acceptable carriers.
  • the ratio of the auxiliary material to the active ingredient of the medicine may be, for example, the active ingredient accounts for 30% to 50% by weight, and the auxiliary material accounts for 70% to 50% by weight.
  • the auxiliary material can be, for example, one or more of sodium hyaluronate, magnesium stearate, sodium alginate, starch, microcrystalline cellulose, chitosan, stachyose, binder or collagen.
  • Figure 1 shows the chemical structure of ginsenoside Rk3
  • Figure 2 is the chemical structure of ginsenoside Rh4
  • FIG. 3 is a graph showing the results of HE staining of mouse liver tissue in Example 4.
  • FIG. in is a graph showing the results of HE staining of mouse liver tissue in Example 4.
  • the present invention provides a pharmaceutical composition that can be used to prevent and/or treat alcoholic fatty liver, which contains as active ingredients an effective amount of ginsenoside Rk3 and Ginsenoside Rh4 and a pharmaceutically acceptable carrier,
  • the weight ratio of the ginsenoside Rk3 and the ginsenoside Rh4 is 1:0.5-2.
  • ginsenoside Rk3 refers to the compound as shown in Fig. 1, and its molecular formula is C 36 H 60 O 8 .
  • the above-mentioned ginsenoside Rk3 is a known compound, which can be prepared by methods known in the art, for example, by adding an organic acid solution to the triol group ginsenoside under high temperature and high pressure conditions to obtain a higher purity ginsenoside Rk3 after a directional conversion reaction.
  • the crude product is purified by high performance liquid phase separation and other methods to obtain pure ginsenoside Rk3 with a purity of ⁇ 98%.
  • ginsenoside Rh4 refers to the compound shown in Figure 2 and its molecular formula is C 36 H 60 O 8 .
  • the above-mentioned ginsenoside Rh4 is a known compound, which can be prepared by methods known in the art, for example, by adding an organic acid solution of triol group ginsenoside, and undergoing a directional conversion reaction under high temperature and high pressure conditions, and then undergoing separation and purification to obtain a purity of ⁇ 98 % Pure ginsenoside Rh4.
  • the pharmaceutical composition of the present invention may or may not contain other ginsenosides.
  • the content of the ginsenoside Rk3 and ginsenoside Rh4 is preferably 50 parts by weight or more, more preferably 60 parts by weight or more, more preferably 70 parts by weight or more, more preferably 80 parts by weight or more, more preferably 90 parts by weight or more, more preferably 95 parts by weight or more, more preferably 99 parts by weight or more, more preferably 100 parts by weight (That is, the pharmaceutical composition only contains the above two ginsenosides), based on 100 parts by weight of the total ginsenosides contained in the pharmaceutical composition.
  • the purity of ginsenoside Rk3 used in the pharmaceutical composition of the present invention can be more than 98%, and the purity of ginsenoside Rh4 can be more than 98%.
  • the content of the total ginsenosides can be determined by the vanillin method, and the content of the ginsenosides Rk3 and Rh4 can be determined by the HPLC method.
  • the pharmaceutical composition of the present invention may contain other active ingredients for the prevention and/or treatment of alcoholic fatty liver, or may not contain active ingredients for the prevention and/or treatment of alcoholic fatty liver (ie, ginsenoside Rk3 and ginsenoside Rh4 are used as The only active ingredient to prevent and/or treat alcoholic fatty liver).
  • the present invention also provides the use of the pharmaceutical composition of the present invention in the preparation of drugs for the prevention and/or treatment of alcoholic fatty liver.
  • the pharmaceutical composition of the present invention may contain pharmaceutically acceptable carriers, such as excipients.
  • pharmaceutically acceptable carriers such as excipients.
  • excipients there are no special restrictions on the excipients in the pharmaceutical composition of the present invention.
  • the excipients commonly used in medicines or health care products in this technical field can be used.
  • the auxiliary materials are starch, dextrin, lactose, mannitol, sodium hypromellose, xanthan gum, protein sugar and the like.
  • the dosage form of the pharmaceutical composition of the present invention may be an oral dosage form or an injection dosage form.
  • the oral dosage form may be a liquid dosage form or a solid dosage form.
  • the oral dosage form may be, for example, a hard capsule, a soft capsule, a sustained-release capsule, a compressed tablet, a sugar-coated tablet, a powder, a granule, a dripping pill, a honey pill, a syrup, or an oral liquid;
  • the injection dosage form may be, for example, a solution type, Suspension type, emulsion type or lyophilized powder.
  • the administration mode of the pharmaceutical composition for preventing and/or treating alcoholic fatty liver can be, for example, oral, drip or injection.
  • tablets When preparing solid preparations for oral administration, after adding excipients and optional binders, disintegrating agents, lubricants, coloring agents, flavoring agents, etc. to the main drug, tablets can be prepared according to conventional methods. , Coated tablets, granules, fine granules, powders, capsules, etc.
  • lactose corn starch, white sugar, glucose, sorbitol, crystalline cellulose, silicon dioxide, etc.
  • binders for example, polyvinyl alcohol, ethyl cellulose, and methyl cellulose can be used.
  • a lubricant for example, magnesium stearate, talc, silicon dioxide, etc. can be used; as a coloring agent, it can be used and allowed to be added to medicines.
  • the coloring agent as the flavoring agent, cocoa powder, menthol, aromatic acid, peppermint oil, borneol, cinnamon powder can be used.
  • the above-mentioned tablets and granules can also be coated with sugar coating, gelatin coating, and other necessary outer coatings.
  • pH regulators, buffers, suspending aids, solubilizers, stabilizers, isotonic agents, preservatives, etc. can be added to the main drug as needed, and then made into intravenous, subcutaneous, and intramuscular injections according to conventional methods .
  • a freeze-dried product can also be prepared by a conventional method.
  • suspending aid examples include methyl cellulose, Tween 80, hydroxyethyl cellulose, gum arabic, tragacanth powder, sodium carboxymethyl cellulose, polyoxyethylene sorbitol monolaurate, and the like.
  • solubilizer examples include polyoxyethylene hydrogenated castor oil, Tween 80, nicotinamide, polyoxyethylene sorbitol monolaurate, polyethylene glycol, and castor oil fatty acid ethyl ester.
  • examples of stabilizers include sodium sulfite and sodium metasulfite; examples of preservatives include methyl paraben, ethyl paraben, sorbic acid, phenol, cresol, and chlorocresol.
  • the pharmaceutical composition of the present invention is administered to a subject to treat tumors.
  • the subject may be a mammal, for example, a human, a rat, a rabbit, a sheep, a pig, a cow, a cat, a dog, a monkey, etc., preferably a human.
  • the pharmaceutical composition of the present invention can be administered orally or parenterally.
  • the dosage varies depending on the degree of symptoms, patient age, sex, weight, differences in sensitivity, application method, application period, application interval, nature of the pharmaceutical preparation, types of active ingredients, etc., and there is no particular limitation, but usually adults (weight 60Kg)
  • the above application amount can usually be applied 1 to 3 times a day.
  • Example 1 Preparation of tablets with ginsenoside Rk3/Rh4 composition for preventing and treating alcoholic fatty liver
  • ginsenoside Rk3 with a purity of ⁇ 98%
  • 200g of ginsenoside Rh4 with a purity of ⁇ 98%
  • 500g of medicinal excipients commonly used in the preparation of tablets mix them uniformly, press, dry, and package to obtain 2000 tablets of the present invention
  • Each tablet contains 150mg of active ingredient.
  • Example 2 Preparation of capsules with ginsenoside Rk3/Rh4 composition for preventing and treating alcoholic fatty liver
  • ginsenoside Rk3 with a purity of ⁇ 98%
  • 100g of ginsenoside Rh4 with a purity of ⁇ 98%
  • 600g of commonly used pharmaceutical excipients mix them evenly, and then fill them into capsules currently on the market to obtain 2000 capsules of the present invention.
  • the effective ingredient content in each capsule is 100mg.
  • ginsenoside Rk3 with a purity of ⁇ 98% and 80g of ginsenoside Rh4 with a purity of ⁇ 98%, and mix them evenly, then add appropriate amount of flavoring crystalline fructose, stachyose, citric acid, pectin, diluent water, and heat Dissolve, uniformly fill, and sterilize to prepare 1,000 bottles of the oral liquid of the present invention, and each bottle of the oral liquid contains 120 mg of active ingredients.
  • mice 100 adult male mice (18-22 grams) were randomly divided into normal control group; model group; dosage group: group 1 of the composition of the present invention in Example 2 (Rk3 15mg/kg, Rh4 15mg); the present invention Composition 2 groups (Rk3 7.5mg/kg, Rh4 22.5mg), composition 3 groups of the present invention (Rk3 22.5mg/kg, Rh4 7.5mg), ginsenoside Rk3 (30mg/kg) group, ginsenoside Rh4 (30mg/ kg) group, polyene phosphatidylcholine (30mg/kg) positive drug control group, ginsenoside Rg1 (30mg/kg) group, ginsenoside CK/Rh1 (CK 15mg/kg, Rh1 15mg/kg) group, 10 groups Except for the normal control group, mice in the other groups were given 50% ethanol once a day by intragastric administration at a dose of 12 mL/kg BW for 4 consecutive weeks.
  • mice in the other groups were given
  • mice in the normal control group were given an equal volume of purified water by gavage.
  • the test drug was formulated into a suspension with purified water, and was given by intragastric administration once a day.
  • the mice in the normal control group and the model control group were given the same amount of purified water by intragastric administration, and the intragastric volume was 10ml/kg/d.
  • the mice were free to eat and drink, weighed twice a week, and adjusted the amount of test samples according to their body weight.
  • the model control group and each sample group were given 50% ethanol once at the end of the experiment.
  • the mice were given 12ml/kg BW by gavage.
  • the negative control group was given purified water and fasted for 16h.
  • Animals were intraperitoneally injected with 60 mg/kg BW pentobarbital sodium solution anesthetized from the abdominal aorta, and blood was collected from the abdominal aorta, and liver tissues were taken for detection of various indicators: serum ALT, AST and LDL, serum TC, serum TG and LDL content, liver Tissue TG content and histopathological examination.
  • CI ⁇ 1 the two drugs have a synergistic effect, when CI ⁇ 0.7, the synergy is very significant (see David H. Kern, Carol R. Morgan, and Susanne U. Hildebrand-Zanki.
  • the weight difference of each group was not statistically significant (P ⁇ 0.05); compared with the blank group, the liver mass and liver coefficient of the model group were significantly increased (P ⁇ 0.01), compared with the model group, the liver coefficients of each administration group were all Significant decrease (P ⁇ 0.05). Among them, the liver coefficient of Rk3/Rh4 group dropped extremely significantly (P ⁇ 0.01). The results of this test showed that each administration group had a significant inhibitory effect on alcohol-induced liver enlargement in mice.
  • the composition 1 of the present invention has a better effect than each single component, and has a synergistic effect (CI value ⁇ 1), compared with the polyene phosphatidylcholine group, ginsenoside Rg1 and ginsenoside CK/Rh1
  • the liver coefficient reduction effect of the composition 1 of the present invention is more significant.
  • Table 2 The effect of the composition of the present invention on the activity of serum ALT and AST in alcoholic fatty liver mice
  • ALT and AST are the hallmark indicators of liver damage.
  • the content of ALT and AST in normal serum is very low. Only after liver damage, ALT and AST in liver cells are released into the blood by cell rupture, and ethanol is produced during liver metabolism. Reactive oxygen can directly cause oxidative damage to liver cells.
  • Table 2 that the serum ALT and AST activities of animals in each administration group are significantly different from those of the model group (P ⁇ 0.05).
  • the Rk3/Rh4 group of the composition of the present invention has extremely different serum ALT and AST activities from the model group. Significantly (P ⁇ 0.01), very significantly lower than the model group, but not significantly different from the blank control group (P>0.05).
  • composition of the present invention can significantly reduce serum levels of alcoholic fatty liver mice Abnormally elevated ALT and AST activities, the composition 1 of the present invention at the same dose compared to each single component and polyene phosphatidylcholine group, ginsenoside Rg1, ginsenoside CK/Rh1 in the same dose of ALT, AST
  • the activity reduction effect is stronger.
  • the combination index CI of ginsenoside Rk3 and ginsenoside Rh4 composition 1 is ⁇ 1
  • the combination index of composition 2 and composition 3 is CI> 1, indicating that the composition 1 of the present invention is good
  • the synergistic effect of serotonin has a good protective effect on liver cell damage caused by drinking.
  • Table 3 The influence of the composition of the present invention on the serum TC, TG, LDL content and liver tissue TG content of alcoholic fatty liver mice
  • the damage of alcohol to liver cells is achieved through free radical-mediated lipid peroxidation.
  • the composition 1 of the present invention can effectively reduce the content of TC and TG in mouse serum and improve The level of LDL inhibits the synthesis of endogenous TC and TG, and improves the distribution of lipids in the body and the deposition of internal organs.
  • liver of the control group is normal in size, with red color, soft texture, and sharp edges; the liver of the model group is obviously enlarged, gray-white, grainy, and the cut surface is greasy; each The liver morphology of the treatment group was improved compared with the model group, but the liver morphology of the Rk3/Rh4 composition was closer to that of the control group than the other treatment groups of R.
  • the results of HE staining of the liver ( Figure 3, 1-10) showed that the liver cells in the control group were normal in size and morphology, neatly arranged, with a large and round nucleus visible in the center, and the cytoplasm was evenly colored.
  • lipid droplets were deposited in the liver cells, and the morphology and structure were normal, without steatosis and inflammation; the liver cells in the model group were swollen and the boundaries were unclear.
  • the fatty degeneration cells are distributed in a focal shape.
  • the liver tissue is almost replaced by fatty vacuoles.
  • the hepatocytes are balloon-like degeneration, and there are inflammatory cell infiltration in the portal area; human saponin Rk3 , Rh4 single action group, composition 2 group, composition 3 group, positive drug control group, ginsenoside Rg1 group, and ginsenoside CK/Rh1 group.
  • mice fed with the Rk3/Rh4 composition 1 of the present invention had almost no lipid droplet deposition in the liver cells in the liver tissue, the morphology and structure were close to normal, and there was no steatosis.
  • the disclosed Rk3/Rh4 composition can better improve the degree of liver steatosis in mice caused by alcohol.
  • Example 4 The normal control group in Example 4; model group; Rk3 group, Rh4 group, Rk3/Rh4 group in liver superoxide dismutase (SOD), liver reduced glutathione (GSH), and liver malondioxide Aldehyde (MDA) level; and molecular chip screening to determine the expression level of related genes in hepatocytes, and the test results are based on the mean plus or minus the standard deviation Indicates that the statistical processing method uses one-way analysis of variance;
  • the liver cells of alcoholic fatty liver are very susceptible to oxidative stress.
  • the model group mice have weakened antioxidant capacity, which is manifested by increased levels of MDA, a harmful product of alcohol metabolism, decreased liver tissue SOD activity, and decreased levels of reduced glutathione GSH.
  • MDA manganese-associated dihydroxyase
  • GSH glutathione
  • composition of the present invention has a statistical table showing the relative expression of genes related to important metabolic pathways in alcoholic fatty liver mice
  • ⁇ the corresponding gene is down-regulated fold in liver cell mRNA expression
  • ⁇ indicates the corresponding gene is up-regulated fold in liver cell mRNA expression.
  • Fatty acid synthase which plays a vital role in fatty acid synthesis, is responsible for all the catalytic steps for the de novo synthesis of acetyl-CoA and malonyl-CoA to a long-chain palmitate (palmitate).
  • This gene The expression directly affects the amount of fatty acid synthase and plays an important role in controlling animal fat deposition.
  • Lipoprotein lipase (LpL) is one of the key enzymes of fat metabolism. It acts on lipoproteins and mainly decomposes triacylglycerols in lipoproteins. It is the rate-limiting enzyme for removing triacylglycerols in plasma and promotes the transfer of cholesterol from lipoproteins.
  • Scd1 Sterol-CoA desaturase 1
  • LpL Phospholipids and apolipoprotein
  • LpL also has the ability to increase the ability of chylomicrons to bind to LP receptors, and promote the uptake of chylomicrons.
  • Sterol-CoA desaturase 1 (Scd1) is the rate-limiting enzyme of monounsaturated fatty acid biosynthesis. It plays a central regulatory role in fatty acid metabolism and is also one of the target genes of leptin; leptin and diabetes , Obesity and fatty liver are closely related and are one of the hotspots of metabolic diseases in recent years.
  • the model group can increase the synthesis of Fasn and decrease the synthesis of LpL, which is the culprit leading to excessive fat deposition in liver cells and the primary factor in the occurrence of fatty liver; and each group of administration can reduce the synthesis of Fasn, the administration group Rh4 and the composition Rk3/Rh4 can significantly increase LpL synthesis, reduce fatty acid synthesis in liver tissue, strengthen lipolysis, and have a positive effect on alleviating liver fatness.
  • the up-regulation of Scd1 gene expression in the model group may be one of the most important molecular mechanisms that cause alcoholic steatosis, but each administration group can significantly down-regulate the expression of Scd1 gene.
  • composition of the present invention has the effect of preventing and treating alcoholic fatty liver, and it has no side effects after long-term use.
  • the present invention provides a pharmaceutical composition containing ginsenosides Rk3 and Rh4, which is synergistic and has the effect of preventing and/or treating alcoholic fatty liver.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

La présente invention divulgue une composition de ginsénoside présentant une fonction de prévention et de traitement de la stéatose hépatique alcoolique. La composition pharmaceutique pouvant être utilisée pour prévenir et/ou traiter la stéatose hépatique alcoolique selon la présente invention contient une dose prophylactiquement et/ou thérapeutiquement efficace de ginsénoside Rk3 et de ginsénoside Rh4 comme principes actifs, et un véhicule pharmaceutiquement acceptable. Dans la composition pharmaceutique, le rapport massique entre le ginsénoside Rk3 et le ginsénoside Rh4 est de 1/0,5-2, et est de préférence de 1/0,9-1,1. La composition de ginsénoside selon la présente invention peut nettement améliorer les anomalies de l'indice de la fonction hépatique provoquées par une grande quantité de consommation d'alcool, réduisant la génération d'infiltrats inflammatoires et de vacuoles de graisse dans le tissu hépatique. La présente invention concerne une composition pharmaceutique à interaction synergique contenant les ginsénosides Rk3 et Rh4 et présentant des effets de prévention et/ou de la stéatose hépatique alcoolique.
PCT/CN2021/088142 2020-04-17 2021-04-19 Composition de ginsénoside présentant une fonction de prévention et de traitement de la stéatose hépatique alcoolique WO2021209070A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2021257523A AU2021257523B2 (en) 2020-04-17 2021-04-19 Ginsenoside composition having alcoholic fatty liver-preventing and -treating function

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202010305247.XA CN111388490B (zh) 2020-04-17 2020-04-17 一种具有防治酒精性脂肪肝功能的人参皂苷组合物
CN202010305247.X 2020-04-17

Publications (1)

Publication Number Publication Date
WO2021209070A1 true WO2021209070A1 (fr) 2021-10-21

Family

ID=71417622

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2021/088142 WO2021209070A1 (fr) 2020-04-17 2021-04-19 Composition de ginsénoside présentant une fonction de prévention et de traitement de la stéatose hépatique alcoolique

Country Status (3)

Country Link
CN (1) CN111388490B (fr)
AU (1) AU2021257523B2 (fr)
WO (1) WO2021209070A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111388490B (zh) * 2020-04-17 2021-07-02 陕西巨子生物技术有限公司 一种具有防治酒精性脂肪肝功能的人参皂苷组合物
CN116023423B (zh) * 2023-03-29 2023-06-27 中国农业科学院特产研究所 人参皂苷Rk3及制备和在制备毛囊炎药物中的应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20150019337A (ko) * 2013-08-13 2015-02-25 주식회사 한국인삼공사 진세노사이드 Rh4 강화 분획물을 유효성분으로 함유하는 항염 또는 항산화용 약학적 조성물
CN106109483A (zh) * 2016-07-29 2016-11-16 陕西巨子生物技术有限公司 具有抗肿瘤活性的二醇组/三醇组稀有人参皂苷组合物
CN108685931A (zh) * 2018-07-02 2018-10-23 南京类人生物材料有限公司 具有降糖活性的人参皂苷组合物及其应用
CN109394703A (zh) * 2018-07-05 2019-03-01 西安巨子生物基因技术股份有限公司 人参皂苷Rk3静脉注射制剂及制备方法
CN111388490A (zh) * 2020-04-17 2020-07-10 陕西巨子生物技术有限公司 一种具有防治酒精性脂肪肝功能的人参皂苷组合物

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103054906B (zh) * 2012-11-30 2014-09-10 周斌 用于解酒的蜂胶乙醇提取物、制备方法及在生产口含片中的应用

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20150019337A (ko) * 2013-08-13 2015-02-25 주식회사 한국인삼공사 진세노사이드 Rh4 강화 분획물을 유효성분으로 함유하는 항염 또는 항산화용 약학적 조성물
CN106109483A (zh) * 2016-07-29 2016-11-16 陕西巨子生物技术有限公司 具有抗肿瘤活性的二醇组/三醇组稀有人参皂苷组合物
CN108685931A (zh) * 2018-07-02 2018-10-23 南京类人生物材料有限公司 具有降糖活性的人参皂苷组合物及其应用
CN109394703A (zh) * 2018-07-05 2019-03-01 西安巨子生物基因技术股份有限公司 人参皂苷Rk3静脉注射制剂及制备方法
CN111388490A (zh) * 2020-04-17 2020-07-10 陕西巨子生物技术有限公司 一种具有防治酒精性脂肪肝功能的人参皂苷组合物

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BAEK SEUNG-HOON, SHIN BYONG-KYU, KIM NAM JAE, CHANG SUN-YOUNG, PARK JEONG HILL: "Protective effect of ginsenosides Rk3 and Rh4 on cisplatin-induced acute kidney injury in vitro and in vivo", JOURNAL OF GINSENG RESEARCH, vol. 41, no. 3, 1 July 2017 (2017-07-01), KR , pages 233 - 239, XP055857137, ISSN: 1226-8453, DOI: 10.1016/j.jgr.2016.03.008 *
QU LINLIN; ZHU YANYAN; LIU YANNAN; YANG HAIXIA; ZHU CHENHUI; MA PEI; DENG JIANJUN; FAN DAIDI: "Protective effects of ginsenoside Rk3 against chronic alcohol-induced liver injury in mice through inhibition of inflammation, oxidative stress, and apoptosis", FOOD AND CHEMICAL TOXICOLOGY, vol. 126, 1 January 1900 (1900-01-01), GB , pages 277 - 284, XP085632620, ISSN: 0278-6915, DOI: 10.1016/j.fct.2019.02.032 *

Also Published As

Publication number Publication date
CN111388490B (zh) 2021-07-02
CN111388490A (zh) 2020-07-10
AU2021257523A1 (en) 2022-12-22
AU2021257523B2 (en) 2024-03-21

Similar Documents

Publication Publication Date Title
US8703215B2 (en) Agents from Ficus hispida for the amelioration of metabolic syndrome and related diseases
WO2021209070A1 (fr) Composition de ginsénoside présentant une fonction de prévention et de traitement de la stéatose hépatique alcoolique
US20060263459A1 (en) Sea Buckthorn Compositions and Associated Methods
Kim et al. Comparison of the antiobesity effects of the protopanaxadiol‐and protopanaxatriol‐type saponins of red ginseng
US10702519B2 (en) Use of methoxatin, derivative and/or salt thereof in Sjogren's syndrome and pharmaceutical composition
EP2685997B1 (fr) Composition contenant un extrait d'une combinaison d'herbes utilisable en vue de la prévention ou du traitement de la neuropathie diabétique périphérique
US20150306165A1 (en) Plant extract composition for inhibiting adipocytes, reducing body fat, promoting weight loss and increasing lipid metabolism as well as application thereof
CN102205011A (zh) 一种具有减肥功能的药物组合物
WO2021197372A1 (fr) Composition antitumorale contenant des ginsénosides rares rk2, ck et ppt
Salama et al. Experimental and therapeutic trials of amygdalin
EP3081097B1 (fr) Composition pour le traitement de l'infertilité
KR101685876B1 (ko) 길경추출물을 유효성분으로 포함하는 비만 예방 또는 치료용 약학적 조성물
WO2021213232A1 (fr) Application d'une composition de médecine chinoise traditionnelle dans la préparation d'un médicament pour traiter ou prévenir l'hyperlipidémie
US20200268825A1 (en) NEUPANEX®: Neuroprotective, Neuroregenerational, & Neurogenesis Supporting Supplement Combination
TW200816983A (en) Anthracenedione compounds
CN108420890B (zh) 一种具有降血脂作用的组合物及其制备方法
JP2022110113A (ja) エンテロコッカス・フェカーリス、その培養液またはその死菌体を有効成分として含有する筋肉の減退、低下及び筋萎縮の予防、改善または治療用の薬学組成物、食品組成物及び食品添加剤
US20070298136A1 (en) Cholesterol regulating agent
WO2016124080A1 (fr) 20(r)-ginsenoside rg3 destiné à la préparation d'un médicament pour la prévention et/ou le traitement de l'obésité ou ses applications et médicament associé
EH Protective effects of Echinacea on cyproterone acetate induced liver damage in male rats
Luzia et al. Yerba mate (Ilex paraguariensis A. St. Hil) and risk factors for cardiovascular diseases
CN111467385B (zh) 组合物在预防或治疗神经退行性疾病中的用途
WO2018177340A1 (fr) Composition de réduction du poids et de réduction de la graisse corporelle et produit pharmaceutique et application correspondants
KR101572311B1 (ko) 2-아미노-2-노보네인카르복실산을 함유하는 비만 예방 또는 치료용 조성물
CN116327792B (zh) 安格洛苷c及组合物治疗甲亢及相关疾病的医疗新用途

Legal Events

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

Ref document number: 21788104

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2021257523

Country of ref document: AU

Date of ref document: 20210419

Kind code of ref document: A

122 Ep: pct application non-entry in european phase

Ref document number: 21788104

Country of ref document: EP

Kind code of ref document: A1

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 23.05.2023)

122 Ep: pct application non-entry in european phase

Ref document number: 21788104

Country of ref document: EP

Kind code of ref document: A1