21 results about "Obeticholic acid" patented technology

The invention discloses a synthesis method of N-goose deoxycholyl-L-aspartic acid and application of the N-goose deoxycholyl-L-aspartic acid in preparation of a medicine for improving metabolism-related fatty liver diseases. According to the method provided by the invention, chenodeoxycholic acid and L-dimethyl aspartate hydrochloride are taken as raw materials, and a chenodeoxycholic acid-dimethyl aspartate intermediate is synthesized, so that a target compound-N-chenodeoxycholyl-L-aspartic acid with a brand new structure is efficiently prepared. The compound shows a treatment effect superior to that of obeticholic acid (OCA) in an animal model, and can effectively improve multiple indexes such as fatty degeneration, inflammation and fibrosis of the liver. The invention provides a brand new solution for major clinical challenges of insufficient curative effect, large side effect, drug withdrawal rebound and the like of the current MAFLD treatment drug, and provides a candidate compound with a wide prospect for developing a novel efficient MAFLD treatment drug.

The invention specifically discloses a novel chalcone compound as well as a preparation method, a pharmaceutical composition and application thereof. Experimental results show that the compound shows remarkable anti-inflammatory activity in a lipopolysaccharide stimulated RAW 264.7 cell model, and the anti-inflammatory activity is obviously superior to that of a positive drug dexamethasone; the compound shows a remarkable lipid accumulation inhibition effect in a HepG2 cell model treated by free fatty acid, is obviously superior to a positive drug obeticholic acid, and can be used for developing drugs for treating the non-alcoholic fatty liver disease, including but not limited to simple fatty liver, non-alcoholic steatohepatitis and related liver cirrhosis.

The present application relates to the technical field of biological medicine, and in particular to a pharmaceutical composition for treating hepatocellular carcinoma and application thereof, wherein the pharmaceutical composition comprises metformin or a pharmaceutically acceptable salt thereof and obeticholic acid or a pharmaceutically acceptable salt thereof, and the weight ratio of the metformin to the obeticholic acid is 1:0.05-0.2. It is found for the first time that the combination of metformin and farnesol X receptor agonist can regulate the AMPK / mTOR pathway and the immune recruitment mediated by CXCL16 in a synergistic manner, inhibit the proliferation of tumor cells, repair the recruitment function of NKT cells in the microenvironment of hepatocellular carcinoma, and realize the dual anti-tumor effect of metabolic inhibition and immune enhancement. Animal experiments show that the tumor inhibition rate of the combination drug group is significantly better than that of the single drug group, and the safety is good.

The application discloses a synthesis method of N-chenodeoxycholyl-L-aspartic acid and application of the N-chenodeoxycholyl-L-aspartic acid in preparation of a medicine for improving metabolic associated fatty liver disease. The method provided by the application uses chenodeoxycholic acid and L-aspartic acid dimethyl ester hydrochloride as raw materials, synthesizes a chenodeoxycholic acid-aspartic acid dimethyl ester intermediate, and efficiently prepares a target compound, N-chenodeoxycholyl-L-aspartic acid, which is a novel structure, the compound exhibits a treatment effect superior to that of obeticholic acid (OCA) in an animal model, and can effectively improve multiple indexes such as liver steatosis, inflammation and fibrosis. The application provides a novel solution for major clinical challenges such as insufficient treatment effect, large side effect and rebound after drug withdrawal of current MAFLD treatment medicines, and provides a candidate compound with broad prospects for developing a new high-efficiency MAFLD treatment medicine.

This invention relates to the field of biomedical materials technology and provides an application of obeticholic acid-exosome nanoparticles in the treatment of hepatic ischemia-reperfusion injury. The obeticholic acid-exosome nanoparticles are prepared by combining exosomes and obeticholic acid using an ultrasonic method, wherein the exosomes are derived from human bone marrow mesenchymal stem cells. The method for preparing the obeticholic acid-exosome nanoparticles is simple and easy to mass-produce. By utilizing exosomes derived from mesenchymal stem cells, the obeticholic acid-exosome nanoparticles improve the drug's targeting in vivo and prolong its circulation time, achieving targeted delivery of obeticholic acid to the liver, thus providing a new targeted therapeutic strategy for hepatic ischemia-reperfusion injury.

This invention specifically discloses a novel chalcone compound, its preparation method, pharmaceutical composition, and applications. Experimental results show that this compound exhibits significant anti-inflammatory activity in a lipopolysaccharide-stimulated RAW 264.7 cell model, significantly superior to the positive control drug dexamethasone; and in a free fatty acid-treated HepG2 cell model, it exhibits significant inhibition of lipid accumulation, significantly superior to the positive control drug obeticholic acid. It can be used to develop drugs for the treatment of non-alcoholic fatty liver disease, including but not limited to simple fatty liver, non-alcoholic steatohepatitis, and related cirrhosis.

The present invention relates to obeticholic acid:or a pharmaceutically acceptable salt, solvate or amino acid conjugate thereof. Obeticholic acid is useful for the treatment or prevention of a FXR mediated disease or condition, cardiovascular disease or cholestatic liver disease, and for reducing HDL cholesterol, for lowering triglycerides in a mammal, or for inhibition of fibrosis. The present invention also relates to processes for the synthesis of obeticholic acid.

This invention discloses the application of lomestatide and its compositions in the preparation of drugs for treating liver fibrosis. The Jin Zhengjun Q-value method is a classic synergistic discriminant model. Cell experiments based on this model show that lomestatide and obeticholic acid exhibit significant synergistic anti-liver fibrosis effects in a molar ratio of 1:2.5 to 1:10, achieving a synergistic effect greater than the sum of its parts (1+1>2). Therefore, compositions of lomestatide and obeticholic acid in a molar ratio of 1:2.5 to 1:10 show promise for development into drugs for treating liver fibrosis. Furthermore, prior art has not disclosed any therapeutic effect of lomestatide on liver fibrosis; therefore, lomestatide also shows promise for development into a drug for treating liver fibrosis.

The invention relates to the field of medicine, in particular to solid dosage forms for the treatment of primary biliary cholangitis (PBC). The invention provides a modified release solid dosage form comprising two active pharmaceutical ingredients, obeticholic acid and ursodeoxycholic acid, arranged to release sequentially over time. The solid dosage form is designed to achieve a controlled, separate release of each API to provide a desired therapeutic profile.

Provided herein are methods of treating Alager's Syndrome (ALGS) using an ileum bile acid transport (IBAT) inhibitor (e.g., Ovixabet or a pharmaceutically acceptable salt thereof). These methods may include reducing itch score, serum bile acid concentration, increasing height, normalizing weight, improving sleep, and improving liver parameters.

The invention belongs to the technical field of biological medicine, and particularly relates to application of an FXR agonist as a radiation sensitizer in preparation of anti-liver cancer drugs, in particular to application of obeticholic acid (OCA) combined radiation in treatment of liver cancer. When an FXR agonist OCA is used for activating FXR, it is found that activation of FXR can inhibit STAT3 phosphorylation by targeting SOCS3 to inhibit tumor stem cells, and OCA combined radiation can kill tumor stem cells more effectively. OCA can be used as a radiation sensitizer to enhance the killing effect of liver cancer stem cells.

The present invention discloses a preparation method of obeticholic acid, and the preparation method comprises the following steps: S1. A compound of formula (I) reacts with acetylene under the conditions of a metal iridium bipyridine catalyst, a base and light to generate a compound of formula (II); S2. The compound of formula (II) is subjected to a reduction reaction to form a compound of formula (III); S3. The hydroxyl group of the compound of formula (III) is protected, and then it reacts with 4-tert-butylaniline to generate a compound of formula (IV); S4. The compound of formula (IV) undergoes a coupling reaction with a compound of formula (V-1) to obtain obeticholic acid; R is bromine or chlorine. The preparation method of the present invention has fewer reaction steps, reduces the use of metal reagents, improves the preparation yield of obeticholic acid, is more efficient and economical, and is environmentally friendly. #imgabs0#

The application discloses a complex of ursodeoxycholic acid or obeticholic acid and teprenone and application of the complex in preparation of a medicine for preventing and treating liver fibrosis. The combination of ursodeoxycholic acid or obeticholic acid and teprenone can significantly reduce the levels and contents of glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminase (AST) and hydroxyproline (Hyp) in model mice, thereby the effect of ursodeoxycholic acid or obeticholic acid in treating liver fibrosis can be enhanced. Therefore, the complex of ursodeoxycholic acid or obeticholic acid and teprenone has a potential for preventing and treating liver fibrosis, which is superior to ursodeoxycholic acid or obeticholic acid single component.

The present disclosure is directed to bilayer tablet pharmaceutical compositions comprising a first layer comprising obeticholic acid (OCA) or a pharmaceutically acceptable salt, solvate, or amino acid, sulfate or glucuronide conjugate, or prodrug thereof; and a second layer comprising bezafibrate or a pharmaceutically acceptable salt or ester thereof. Related compositions and methods of making and using the compositions are disclosed.

The present invention relates to methods for the expansion of cholangiocytes in vitro that comprise culturing the cholangiocytes in the presence of a farnesoid X receptor (FXR) agonist, such as chenodeoxylic acid (CDA) or obeticholic acid (OCA). The FXR-treated cholangiocytes and organoids obtained by the methods may be useful for example for the treatment of biliary disorders and compound screening. Also provided are kits and uses of culture media for the production of FXR-treated cholangiocyte organoids.

Disclosed are methods of treating or reducing the occurrence of a steatohepatitis disorder. The disorder may include, for example, NASH, parenteral nutrition associated liver disease (PNALD), or genetic forms of liver disease. The method may comprise the step of administering a composition comprising obeticholic acid to an individual in need thereof.

The application provides application of obeticholic acid in prevention and treatment of acute hepatopancreas necrosis disease of shrimp, and belongs to the technical field of shrimp breeding disease prevention and control. The application adopts a kind of bile acid metabolism regulator, obeticholic acid (OCA), controls the metabolism of bile acid of diseased shrimp, reduces the accumulation of bile acid in the hepatopancreas of shrimp, and reduces the hepatopancreas damage caused by pathogenic vibrio infection. No matter injection or adding to feed, obeticholic acid significantly reduces the symptoms and mortality of shrimp after infection of acute hepatopancreas necrosis disease, which shows that obeticholic acid has certain application value in prevention and treatment of acute hepatopancreas necrosis disease of shrimp.

The invention discloses a preparation method and application of resveratrol prodrug-obeticholic acid nanoparticles, and the preparation method comprises the following steps: (1) dissolving resveratrol in an organic alkali and a solvent, dropwise adding an oxalyl chloride solution for reaction, then adding mPEG-OH for continuous stirring, after the reaction is finished, removing the solvent, and performing dialysis and freeze drying to obtain a Res prodrug polymer PRO; (2) PRO and OCA are dissolved in an organic solvent, deionized water is slowly added under stirring to achieve self-assembly, then PRO / OCANPs is obtained through dialysis, and the nanoparticles aim at specifically targeting tumor sites and are decomposed to release Res and OCA under the action of ROS in a tumor microenvironment, so that the treatment effect is achieved to the maximum extent.

A method of treating reduced pulmonary function by administering an effective dose of a Farnesoid X Receptor (FXR) agonist, particularly obeticholic acid, is disclosed. Also disclosed is an in vivo animal model of lung injury and altered functioning, useful for identifying compounds active in restoring pulmonary function.

The disclosure relates to obeticholic acid formulations with improved stability, dissolution, and / or solubility, methods of preparing the same for use and methods of treating various diseases and conditions.

The present invention relates to co-crystals of 1, 1-dioxo-3, 3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-alpha-[N-((S)-1-carboxylpropyl) carbamoyl]-4-hydroxybenzyl} carbamoylmethoxy)-2, 3, 4, 5-tetrahydro-1, 2, 5-benzothiadiazepine (Ovicobatide) and a pyridoxine, in particular to co-crystals of 1, 1-dioxo-3, 3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-alpha-[N-((S)-1-carboxylpropyl) carbamoyl]-4-hydroxybenzyl} carbamoylmethoxy)-2, 3, 4, 5-tetrahydro-1, 2, 5-benzothiadiazepine (Ovicobatide). The invention also relates to pharmaceutical compositions comprising said co-crystals, and their use in the treatment of various conditions as described herein.