271 results about "Chenodeoxycholic acid" patented technology

The invention relates to a method for preparing binding-form ursodesoxycholic acid by a two-step enzymatic method, belonging to the field of biotechnology. Under the water solution state, a substrate, namely binding-form chenodeoxycholic acid, is converted into the binding-form ursodesoxycholic acid in the presence of 7alpha-HSDH and 7beta-HSDH, the separation is not needed in the intermediate step, thus the method disclosed by the invention is very simple, and furthermore, the conversion efficiency is very high. Especially chicken bile, duck bile or goose bile in a mixture form can be subjected to reaction without separating and purifying the binding-form chenodeoxycholic acid. The preparation process is simple and easy to implement, and the new, simple and convenient preparation method is provided for the binding-form ursodesoxycholic acid.

The invention provides a method for catalyzing chenodeoxycholic acids to compound ursodesoxycholic acids through efficient whole-cells. A 7a-hydroxysteroid dehydrogenase (7a-HSDH) and a lactic dehydrogenase (LDH) for regeneration of coenzyme nicotinamide adenine dinucleotide (NAD) are efficiently co-expressed in escherichia coli, escherichia coli whole cells are used to catalyze chenodeoxycholic acids (CDCA) to generate 3 alpha (Alpha)-hydroxyl-7-oxo-5bata (Beta)- cholanic acids (7-KLCA), and a reaction liquid which is obtained by catalyzing the chenodeoxycholic acids through whole cells is adjusted to be 7-KLCA crude products. Reconstitution cells can be easily obtained in low cost through a fermentation process, are better than a chemical synthesis method in production cost and product quality, and are suitable for commercial process.

The invention provides a preparation method for 5 beta-3 alpha, 7 alpha-dihydroxy-6 alpha-ethyl-cholanic acid. The method comprises the following steps: carrying out silanization on 5 beta-3 alpha-ethoxy carbonyloxy-7-carbonyl-methyl cholanate by silicon haloganide in an aprotic solvent in the presence of strong alkali, producing a mukaiyama aldol reaction, reducing 5 beta-3 alpha-ethoxy carbonyloxy-6-ethylidene-7-carbonyl-methyl cholanate by palladium carbon and hydrogen, and hydrolyzing to obtain 5 beta-3 alpha-hydroxy-6 alpha-ethyl-7-carbonyl-cholanic acid; finally, reducing 5 beta-3 alpha-hydroxy-6 alpha-ethyl-7-carbonyl-cholanic acid by sodium borohydride to obtain 6-ECDCA (6 alpha-ethyl-chenodeoxycholic acid). The raw materials adopted in the method are wide in source; only one-step siloxane protection is required, so that a process is simple; the product yield is high.

The invention relates to a preparing method of a chenodeoxycholic acid derivative, and particularly relates to a preparing method of a compound shown as a formula I. The method includes (1) subjecting a compound shown as a formula 1 to Swern oxidation to obtain a compound shown as a formula 2; (2) subjecting the compound shown as the formula 2 to hydroxy protection to obtain a compound shown as a formula 3; (3) bringing the compound shown as the formula 3 into contact with iodoethane to obtain a compound shown as a formula 4; (4) subjecting the compound shown as the formula 4 to a reduction reaction to obtain a compound shown as a formula 5; and (5) bringing the compound shown as the formula 5 into contact with hydrogen under the existence of palladium / carbon that is a catalyst to obtain the compound shown as the formula I. The method is short in steps, simple in operation, and suitable for industrial production, and raw materials are easily available.

The invention relates to a total bile acid extract of bear bile powder and a preparation method and application of injection thereof. The total bile acid extract of the bear bile powder is prepared by the following steps of: performing reflux extraction on the bear bile powder by using ethanol; recovering the ethanol from extracting solution, and concentrating the extracting solution; and performing alkaline hydrolysis, neutralization, acidification, ethyl acetate extraction, ethyl acetate crystallization and ethanol crystallization. The invention also provides a method for preparing the injection from the total bile acid extract of the bear bile powder. The prepared total bile acid extract of the bear bile powder and the injection thereof can be used for preparing medicaments for resisting bacteria and viruses, relieving cough and reducing sputum and protecting liver and gallbladder. The invention can improve the extraction yield and purity of ursodesoxycholic acid in the total bile acid extract of the bear bile powder and reduce the chenodeoxycholic acid content simultaneously, so the ursodesoxycholic acid content in the total bile acid extract of the bear bile powder is no less than 70 percent and the chenodeoxycholic acid content is no more than 20 percent. The ursodesoxycholic acid content in the total bile acid extract of the bear bile powder is higher, and the ursodesoxycholic acid yield is high and is over 18 percent generally.

The invention discloses an ursodesoxycholic acid preparation method. The method comprises the following steps: 1, adding chenodeoxycholic acid and a solvent A to a reaction container, stirring for dissolving, adding 7-alphaHSDH, 7-betaHSDH and a coenzyme II, and carrying out a reaction at a controlled temperature at a controlled pH value to convert chenodeoxycholic acid into ursodesoxycholic acid in order to obtain a conversion liquid; 2, heating the conversion liquid obtained in step 1 to denaturalize the 7-alphaHSDH and the 7-betaHSDH, centrifuging through a high speed centrifuge, removing proteins, adding a sodium hydroxide solution to the above obtained solution, distilling to remove the solvent A, adding water to dissolve obtained distillation residues, adding an acid, and crystallizing to obtain crude ursodesoxycholic acid; and 3, adding the crude ursodesoxycholic acid obtained in step 2 and a solvent B to the reaction container, heating and refluxing the crude ursodesoxycholic acid and the solvent B for 1h, cooling the obtained reaction product to normal temperature, and filtering the cooled product to obtain ursodesoxycholic acid with the purity being greater than 99%. The ursodesoxycholic acid preparation method has the advantages of simple technology, short synthesis route, high conversion rate, easy post-treatment and environmental protection.

The invention discloses a method for purifying chenodeoxycholic acid. The method comprises the following steps: pretreatments such as degreasing, decoloration and impurity removal are carried out on commercially available crude bile paste or crude bile powder, so as to obtain a component to undergo chromatographic separation; the component to undergo chromatographic separation undergoes purification and separation by the use of a chromatographic column with a hydrophilic resin filler as a stationary phase; and separation products undergo concentration, acidification, washing and drying, so as to obtain chenodeoxycholic acid. In comparison with the prior art, the invention has the following beneficial effects: 1, content of the main component is high; 2, reappearance is high and operability is good; 3, short cycle: it only takes two days to prepare the high-purity chenodeoxycholic acid product from processing of the bile paste raw material; and 4, low content of organic residues: as processes such as solvent extraction, column chromatography on silica gel and the like in the traditional techniques are abandoned, an industrial chromatographic process with low dosage of an organic solvent is adopted and the final product undergoes drying process, the content of the residual organic solvent in the final product is especially low.

The invention discloses a new thought of generating 7-carbonyl-lithocholic acid by virtue of chenodeoxycholic acid dissolved by NBS acetone peroxide, and carrying out catalytic synthesis on the 7-carbonyl-lithocholic acid (7k-LCA) in combination with biological enzyme catalysis to obtain ursodesoxycholic acid (UDCA). The new thought is characterized by comprising the following steps: generating a catalytic enzyme (7 beta-HSDH) with high purity, high activity and high stability by virtue of the characteristics of high efficiency and low cost of the method of generating 7-carbonyl-lithocholic acid by virtue of chenodeoxycholic acid dissolved by NBS acetone peroxide and in combination with high-density fermentation of recombinant escherichia coli, and selectively catalyzing 7k-lithocholic acid in an aqueous phase to generate the ursodesoxycholic acid (UDCA). The synthesis process is simple, short in synthesis route, high in conversion rate and low in cost, and is a novel method for preparing ursodesoxycholic acid on the basis of a chemical oxidation and enzyme catalysis combination technology.

The invention discloses a method for synthesizing ursodeoxycholic acid (UDCA) and high-chiral-purity D-amino acid based on an enzyme-method coupling technology. The method comprises the following steps: putting chenodeoxycholic acid and alpha-ketonic acid into a solution system containing 7alpha-HSDH (Homoserine Dehydrogenase), DAADH and NADP (Nicotinamide Adenine Dinucleotide Phosphate) and carrying out enzyme catalysis reaction; separating a reaction solution by adopting an ultra-filtration membrane to obtain a concentrated mixed enzyme solution; regulating the pH (Potential of Hydrogen) ofa dialysis solution and crystallizing; filtering and separating to obtain 7-KLCA wet powder and filtrate; carrying out chromatographic treatment on the filtrate to obtain the D-amino acid; putting the7-KLCA wet powder into a solution system containing glucose, the NADP, the 7alpha-HSDH and GDH (Glutamate Dehydrogenase) and carrying out enzyme catalysis reaction; separating the reaction solution by adopting the ultra-filtration membrane to obtain the concentrated mixed enzyme solution; crystallizing, filtering and separating the dialysis solution, so as to obtain ursodeoxycholic acid. By adopting the method provided by the invention, UDCA and the high-chiral-purity D-amino acid can be obtained at the same time, the enzyme utilization rate is high, synthesis steps are simple and the cost isreduced; meanwhile, a metal reduction reagent and an organic solvent do not need to be added in a reaction process and conditions are mild; the method is environmentally friendly and is suitable forindustrial production.

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).