Method for synthesizing ursodesoxycholic acid by using blanking material after extraction of bilirubin from pig gall

A technology of ursodeoxycholic acid and bilirubin, which is applied in the field of synthesis of ursodeoxycholic acid, can solve the problems of production capacity accumulation, environmental pollution, less application of hyocholic acid, etc., and achieve the effect of improving the conversion yield

Active Publication Date: 2022-04-12
CHANGDE YUNGANG BIOTECHNOLOGY CO LTD
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AI Technical Summary

Problems solved by technology

[0002] Ursodeoxycholic acid (UDCA) is the main component of bear bile, and it is also the main active ingredient contained in traditional Chinese medicine. It has a very wide range of clinical applications and excellent medicinal value. The synthesis of oxycholic acid is limited by the source of biological raw materials, resulting in the production of ursodeoxycholic acid can not meet the needs of global use, so extensive research and development of artificial synthesis of ursodeoxycholic acid technology is of great significance
[0003] The synthesis of ursodeoxycholic acid in the prior art mainly adopts high-purity chenodeoxycholic acid and cholic acid to synthesize, and there is also a report of adopting hyodeoxycholic acid and hyodeoxycholic acid to synthesize ursodeoxycholic acid, but now Synthetic technology generally only has a yield of about 30%, plus the loss of purification, the conversion yield of bitter gall is no more than 6‰, and it is necessary to separate chenodeoxycholic acid, hyodeoxycholic acid and hyodeoxycholic acid from each other and purification, making the whole process route cumbersome, high cost, low yield, easy to cause environmental pollution and waste of raw materials
[0004] At present, many domestic enterprises generally treat the leftovers after extracting bilirubin from pig bile as waste liquid, but there are also cases where the leftovers are used better, such as first hydrolyzing pig bile, and then removing goose Separation and purification of oxycholic acid, hyodeoxycholic acid and hyodeoxycholic acid, the process route includes total bile acid saponification or hydrolysis, decolorization, hyodeoxycholic acid precipitation and purification, chenodeoxycholic acid extraction and purification, hyodeoxycholic acid purification etc., the obtained chenodeoxycholic acid is mainly used for the synthesis of ursodeoxycholic acid after multi-step purification; however, the market demand for the obtained hyodeoxycholic acid is not large, and it is easy to cause accumulation of production capacity; the application of hyodeoxycholic acid is seldom, basically no market

Method used

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  • Method for synthesizing ursodesoxycholic acid by using blanking material after extraction of bilirubin from pig gall

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] A method for synthesizing ursodeoxycholic acid from pig gall to extract bilirubin, the process steps are as follows:

[0022] 1. Take 1000g of pig bile after extracting bilirubin, add 0.1g of 7α-cholanate dehydrogenase to 1000g of pig bile, and add 0.01g of coenzyme NAD + , add 0.2g acetone reductase, use acetone reductase to reduce acetone to isopropanol and accept H source, the temperature during the reaction is controlled at 25°C, T-CDCA is oxidized to T-7K-LCA, T-HCA is oxidized to T-7K-HCA, through HPLC and TLC inspection, T-CDCA and T-HCA residues are less than 1%, the reaction is terminated, the total conversion rate is greater than 95%, and it is ready for use.

[0023] 2. Add 0.1g 7β-cholanate hydrogenase and 0.01g coenzyme NADP to the spare oxidation product in step 1 + , the temperature is controlled at 35°C, 10g of isopropanol is added, the isopropanol is oxidized to acetone to provide H source, and the acetone is recovered by vacuuming under stirring, so t...

Embodiment 2

[0030] A method for synthesizing ursodeoxycholic acid from pig gall to extract bilirubin, the process steps are as follows:

[0031] 1. Take 1000g of pig bile after extracting bilirubin, add 0.2g of 7α-cholanate dehydrogenase to 1000g of pig bile, and add 0.02g of coenzyme NAD + , add 0.3g acetone reductase, use acetone reductase to reduce acetone to isopropanol and accept H source, the temperature during the reaction is controlled at 28°C, T-CDCA is oxidized to T-7K-LCA, T-HCA is oxidized to T-7K-HCA, through HPLC and TLC inspection, T-CDCA and T-HCA residues are less than 1%, the reaction is terminated, the total conversion rate is greater than 95%, and it is ready for use.

[0032] 2. Add 0.2g 7β-cholanate hydrogenase and 0.02g coenzyme NADP to the spare oxidation product in step 1 + , the temperature is controlled at 37°C, 15g of isopropanol is added, the isopropanol is oxidized to acetone to provide H source, and the acetone is recovered by vacuuming under stirring, so t...

Embodiment 3

[0039] A method for synthesizing ursodeoxycholic acid from pig gall to extract bilirubin, the process steps are as follows:

[0040] 1. Take 1000g of pig bile after extracting bilirubin, add 0.3g of 7α-cholanate dehydrogenase to 1000g of pig bile, and add 0.03g of coenzyme NAD + , add 0.4g acetone reductase, use acetone reductase to reduce acetone to isopropanol and accept H source, the temperature during the reaction is controlled at 30°C, T-CDCA is oxidized to T-7K-LCA, T-HCA is oxidized to T-7K-HCA, through HPLC and TLC inspection, T-CDCA and T-HCA residues are less than 1%, the reaction is terminated, the total conversion rate is greater than 95%, and it is ready for use.

[0041] 2. Add 0.3g of 7β-cholanate hydrogenase and 0.03g of coenzyme NADP to the standby oxidation product in step 1 + , the temperature is controlled at 38°C, and 20g of isopropanol is added to oxidize isopropanol to acetone to provide H source, and the acetone is recovered by vacuuming under stirring...

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Abstract

According to the method, chenodeoxycholic acid, hyocholic acid and hyodeoxycholic acid do not need to be separated and purified, but total bile acid in the pig gall subjected to bilirubin extraction is directly catalyzed by a compound enzyme, and then the ursodeoxycholic acid is synthesized by the ursodeoxycholic acid and the pig gall subjected to bilirubin extraction. Compared with the prior art, the method has the advantages that the conversion yield of the ursodesoxycholic acid can be increased by more than one time, meanwhile, the problem that three bile acids and reaction intermediate products thereof are impurities in the prior art is solved, the problem that purification needs to be performed firstly in the traditional conversion method is solved, the use of organic solvents in the reaction process is reduced, and the production cost is reduced. And after the reaction is finished, recycling can be realized, and environmental pollution is reduced.

Description

technical field [0001] The invention relates to the synthesis of ursodeoxycholic acid, in particular to a method for synthesizing ursodeoxycholic acid from the leftovers after extracting bilirubin from pig gall. Background technique [0002] Ursodeoxycholic acid (UDCA) is the main component of bear bile, and it is also the main active ingredient contained in traditional Chinese medicine. It has a very wide range of clinical applications and excellent medicinal value. The synthesis of oxycholic acid is limited by the source of biological raw materials, resulting in the production of ursodeoxycholic acid can not meet the needs of global use, so extensive research and development of artificial synthesis of ursodeoxycholic acid technology is of great significance. [0003] The synthesis of ursodeoxycholic acid in the prior art mainly adopts high-purity chenodeoxycholic acid and cholic acid to synthesize, and there is also a report of adopting hyodeoxycholic acid and hyodeoxychol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P33/02C12P33/06C07J9/00
Inventor 邓家国李刚李国军欧阳文凯胡少东胡建华胡海波肖国兴
Owner CHANGDE YUNGANG BIOTECHNOLOGY CO LTD
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