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209 results about "Ursodeoxycholic acid" patented technology
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Ursodiol is used to dissolve certain types of gallstones, to prevent gallstones from forming in obese patients who are losing weight rapidly, and to treat a certain type of liver disease (primary biliary cirrhosis).
Endoplasmic reticulum stress has been found to be associated with obesity. Therefore, agents that reduce or prevent ER stress may be used to treat diseases associated with obesity including peripheralinsulin resistance, hypergylcemia, and type 2 diabetes. Two compounds which have been shown to reduce ER stress and to reduce blood glucose levels include 4-phenyl butyric acid (PBA), tauroursodeoxycholic acid (TUDCA), and trimethylamine N-oxide (TMAO). Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide and glycerol. The present invention provides methods of treating a subject suffering from obesity, hyperglycemia, type 2 diabetes, or insulin resistance using ER stress reducers such as PBA, TUDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in ER stressed cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating obesity-associated diseases.
The invention discloses a 7beta-hydroxyl steroldehydrogenasemutant which is obtained by proteinengineering and of which coenzyme preference is changed, a coding gene of the 7beta-hydroxyl steroldehydrogenasemutant, a recombinant expression vector and a recombinant expression transformant which contain a sequence of the gene, a preparation method of a recombinant mutantenzyme preparation, andapplication of the recombinant mutant enzyme preparation to preparation of ursodeoxycholic acid. By co-enzyme regeneration of enzymic coupling, the recombinant mutant enzyme preparation disclosed bythe invention can efficiently utilize relatively cheap oxidized coenzyme I (NAD+) instead of very expensive oxidized coenzyme II (NADP+); asymmetric reduction of catalytic 7-hydroxyl lithocholic acideffectively reduces production cost; moreover, the recombinant mutant enzyme preparation has the advantages of simplicity for operation, mild reaction condition, environmental-friendliness, high yieldand the like, and has a good application prospect in preparation of ursodeoxycholic acid by epimerization of chenodesoxycholic acid.
The invention provides a mutant of 7 beta-hydroxyl steroiddehydrogenase, application of the mutant and a synthesis method. The mutant of the 7 beta-hydroxyl steroiddehydrogenase is characterized in that amino acid sequences of the mutant are Seq ID NO:4, and coded nucleotide sequences are Seq ID NO:3; or amino acid sequences of the mutant are Seq ID NO:6, and coded nucleotide sequences are Seq ID NO:5. The mutant, the application and the synthesis method have the advantages that cholic acid compounds, particularly ursodeoxycholic acid, can be catalytically synthesized by the efficient 7 beta-hydroxyl steroiddehydrogenase, mutant enzymes of the 7 beta-hydroxyl steroid dehydrogenase and coenzyme regeneration systems, accordingly, the substrate concentration can reach 100 g / L, the conversion rate is 99.2-99.5%, and the weight yield can reach 94-96%; and the enzymes can be inexpensively and easily obtained by the aid of a fermentation process, accordingly, the production cost and the product quality are superior to the production cost and the product quality of chemical synthesis methods, and the mutant and the synthesis method are applicable to industrial production.
The invention provides a preparation method of ursodeoxycholic acid. Commercial available chenodeoxycholic acid is taken as raw materials, the ursodeoxycholic acid is obtained by four steps including selective oxidation, esterification, deoxidation and hydrolyzation, and the total yield is 85.7%. In a mixture of acetone and water, NBS is used for selective oxidation of hydroxy at C- 7 bit of the chenodeoxycholic acid, and the selective oxidation possesses excellent selectivity and high yield. NaBH14 / CeC13 may be used to deoxidize carbonyl at C-7 bit into hydroxy, and the ratio of alpha / beta is as high as 5 / 95.
A chemical-enzyme method of preparing ursodeoxycholic acid is disclosed. The method adopts chenodeoxycholic acid as an initial substrate, and prepares the ursodeoxycholic acid through a chemical process and a bio-enzyme process in order, wherein 7-KLCA reductase is adopted as a biological catalyst. A situation that an oxidant residual in a process of preparing 7-ketolithocholic acid through a chemical manner causes later enzyme inactivation in the prior art does not occur. A product prepared by the method is high in ee value and low in comprehensive cost.
The invention discloses a method of preparing tauroursodeoxycholic acid by biotransformation and application of the method. Biotransformation includes genetic codon optimization, engineered bacteria construction, engineered bacteria cultivation, substrate transformation and product preparation. Tauroursodeoxycholic acid is prepared by transforming a substrate through direct fermentation of engineered bacteria; the substrate is taurochenodeoxycholic acid. The substrate may reach 250 g / L in concentration; the reaction time is short; substrate transformation rate reaches 98% and above; the obtained product reaches 99% and above in purity; cyclic regeneration of NAD+ (nicotinamide adenine dinucleotide +) in the reaction system helps greatly reduce the usage of the coenzyme NAD+; the cost of enzymic catalytic reaction is reduced; industrial amplification is benefited. hydroxysteroiddehydrogenase and the regenerated coenzyme are connected via a flexible polypeptide sequence to form a protein fusion polymer; binding distances to the substrate and coenzyme are shorter; transformation progress is more facilitated; the number of fermenting times in industrial production is decreased; the process is simplified; time cost and material cost are saved.
The invention relates to novel 7β-hydroxysteroiddehydrogenase mutants, to the sequences which encode these enzyme mutants, to processes for the preparation of the enzyme mutants and to their use in enzymatic reactions of cholic acid compounds, in particular in the preparation of ursodeoxycholic acid (UDCS). The invention also relates to novel processes for the synthesis of UDCS using the enzyme mutants; and to the preparation of UDCS using recombinant, multiply-modified microorganisms.
The invention relates to novel microbial 7alpha-hydroxysteroiddehydrogenase (7alpha-HSDH) knockout mutants and to the use thereof for producing other HSDHs having various functionalities, such as 3alpha-, 7beta- or 12alpha-HSDH, and to the use of thus-produced HSDH enzymes in enzymatic reactions of cholic acid compounds, and in particular for producing ursodeoxycholic acid (UDCS). The invention relates in particular to novel methods for synthesizing UDCS.
The invention discloses an ursodeoxycholic acid nano suspension and a preparation method thereof, relates to the field of pharmaceutical nano formulation, and particularly relates to an ursodeoxycholic acid nano suspension for curing cholestatic cirrhosis and dry powder thereof. The ursodeoxycholic acid nano suspension is characterized by adopting SDS and PVP K30 as surfactants and combining the SDS and the PVP K30 in a weight ratio of 1:1-1:3; and the ursodeoxycholic acid nano suspension has stable quality, with particle size of about 200-800nm. The invention also discloses a preparation method of the suspension.
The invention relates to a productive process for producing ursodeoxycholic acid by using 98.0% bovine and sheep cholic acid, which comprises conducting four steps of esterification, acetylization, oxidization and reduction for bovine and sheep cholic acid, transforming cholic acid with isomer into the structure of anthrodsoxycholic acid to form the compound of anthrodsoxycholic acid, obtaining ursodeoxycholic acid after reaction through utilizing anthrodsoxycholic acid, separating to obtain ursodeoxycholic acid with 98.5% purity by utilizing acetic acidethyl ester. The productive process has simple technical process, low productive cost, and solves the problems of less fowlgall quantity and difficult collection. And the purity of ursodeoxycholic acid which is synthesized is high, which reaches to the international advanced level.
The invention relates to novel 7β-hydroxysteroid dehydrogenases which are obtainable from bacteria of the genus Collinsella, especially of the strain Collinsella aerofaciens, to the sequences encoding said enzymes, to methods for producing said enzymes and to their use in the enzymatic conversion of cholic acid compounds, and especially in the production of ursodeoxycholic acid (UDCS). The invention also relates to novel methods for the synthesis UDCS.
The invention relates to a bile acid-anti-hepatitisvirusdrug conjugate which is shown in the following formula, non-toxic pharmaceutically acceptable salts thereof, a preparation method, a pharmaceutical composition containing the compounds and a use. In the structural formula of figure (I), R represents OH (bile acid) or H (ursodeoxycholic acid), A represents amino acid, n is an integer from 1 to 3, and the structure of the amino acid is D type or L type. D represents the above structure (II).
A preparation method for ursodeoxycholic acid regards chenodeoxycholic acid (1) as raw materials; in technological processes, after adopting corresponding equipment and adding excipient according to the proportional variety and dosage, chemical reactions are carried out through the process flow of an oxidation process (A), a hydrogenation process (B), and a purification process (C) in particular temperature and environmental conditions. In the oxidation process (A), an oxidant (3) and a solvent I 2 are added for oxidation reaction to generate an intermediate (4); in the hydrogenation process (B), a catalyst (6) and a solvent II(5) are added for hydrogenation reaction to get ursodeoxycholic acid crude products (9); in the purification process (C), a passivating agent (11) and a solvent III (10) are added for producing the products of ursodeoxycholic acid (12). The process route of the invention is reasonable; the chemical reactions are mild and safe; the operating conditions are easy to be controlled; the yield is high and the invention makes great progress in the research and production of artificially synthesizing ursodeoxycholic acid (12).
The invention discloses a composition for resisting ageing and improving male energy. The composition is prepared from a raw material and an auxiliary material; the raw material is prepared from the following components in parts by weight: 1-15 parts of nicotinamide mononucleotide, 1-10 parts of protopanoxadiol, 1-9 parts of icarisid I, 2-8 parts of baohuoside I, 3-7 parts of dehydroepiandrosterone and 2-10 parts of ursodesoxycholic acid. The composition is reasonable in composing prescription and proper in compatibility; in the composition, the four of the nicotinamide mononucleotide (NMN), the icarisid I, the baohuoside I and protopanoxadiol are used as monarch drugs together, the composition is capable of comprehensively regulating gonad axis and invigorating kidney-yang and liver, candelay ageing period of the gonad axis and improve the sexual function after being taken for a long time; through intercoordination and synergistic effect of various components, the composition is comprehensive in nutrition, has very good palatability, is particularly suitable for males to take and thus relieving the symptoms of male ageing syndrome and improving the male energy. The invention alsoprovides a preparation containing the composition and a preparation method of the preparation. The preparation method is simple, is moderate in condition and is suitable for industrial batch production.
The invention relates to the field of medicine synthesis, and in particular to chenodeoxycholic acid and a preparation method thereof. The preparation method of the chenodeoxycholic acid provided by the invention comprises the following steps of: using 3 alpha,7 alpha-dihydroxy-5 alpha-ursodeoxycholic acid as raw materials to form an intermediate compound E through chemical reaction; then, performing chemical reaction on the intermediate compound E to form the chenodeoxycholic acid. The structure formula of the intermediate compound E is shown in the description, wherein R1 is alkyl, alkenylor aromatic group; R2 is acyl. The preparation method has the advantages that extracted byproducts can be used as raw materials for fast synthesizing the chenodeoxycholic acid; each step in the process is mild in condition; the yield is high; the method is suitable for mass preparation.