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Production process of ursodeoxycholic acid

A technology for the production of ursodeoxycholic acid, which is applied in the chemical field, can solve the problems of low product quality, unsafe production process, and large consumption of organic solvents, and achieve the effects of high automation, pollution avoidance, and purity improvement

Active Publication Date: 2019-06-25
南京久安源环保科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] (1) High investment cost and high production cost;
[0009] (2) Chemical synthesis requires conditions such as high temperature and high pressure, and a large amount of organic solvents are used, so the production process is unsafe;
[0010] (3), reaction step is many, route is long, and the yield of product is not high;
[0011] (4) Serious pollution and severe environmental problems
[0012] At present, some relevant scientific research institutions have proposed to use whole cells to catalyze the synthesis of ursodeoxycholic acid, but in the catalytic synthesis, the separation of the target product and the whole cell of the catalyst is an insurmountable obstacle, because the viscosity of the catalyzed product is very high, it is not suitable to use traditional methods. The plate and frame press filter will bring more sewage and the degree of automation is low; and the ultrafiltration membrane is not used to remove protein, which will bring a lot of impurities to the later purification, the product quality is not high in purity, and it needs to consume a lot of organic solvents

Method used

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  • Production process of ursodeoxycholic acid
  • Production process of ursodeoxycholic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] as per figure 1 The flow chart for the preparation of ursodeoxycholic acid is shown:

[0045] (1) catalyzing chenodeoxycholic acid through 7α-steroid dehydrogenase, the addition amount is 0.001% of the volume of chenodeoxycholic acid, and the catalysis temperature is 20°C to obtain the catalytic product A;

[0046] (2) The catalytic product A obtained in step (1) is filtered through a microfiltration membrane (the microfiltration membrane is a ceramic membrane, the filtration accuracy is 5nm, the filtration temperature is 20°C, and the filtration pressure is 0.8MPa), to obtain bile acid permeate;

[0047] (3) Add 7β-steroid dehydrogenase to the permeate containing 7-ketolithocholic acid obtained in step (2), in an amount of 0.001% of the volume of the permeate containing 7-ketolithocholic acid, The catalytic temperature is 20°C, and the catalytic reaction is carried out to obtain the catalytic product B;

[0048] (4) The catalytic product B obtained in step (3) is fi...

Embodiment 2

[0055] as per figure 1 The flow chart for the preparation of ursodeoxycholic acid is shown:

[0056] (1) catalyzing chenodeoxycholic acid through bacteria containing 7α-steroid dehydrogenase, the addition amount is 2% of the volume of chenodeoxycholic acid, and the catalysis temperature is 60°C to obtain the catalytic product A;

[0057] (2) The catalytic product A obtained in step (1) is filtered through a microfiltration membrane (the filtration precision is 500 nm, the filtration temperature is 80° C., and the filtration pressure is 0.1 MPa), to obtain a permeate containing 7-ketolithocholic acid;

[0058] (3) In the permeate solution containing 7-ketolithocholic acid obtained in step (2), add the bacterium containing 7β-steroid dehydrogenase, and the amount added is the volume of the permeate solution containing 7-ketolithocholic acid 2%, the catalytic temperature is 60°C, and the catalytic reaction is carried out to obtain the catalytic product B;

[0059] (4) The catal...

Embodiment 3

[0066] as per figure 1 The flow chart for the preparation of ursodeoxycholic acid is shown:

[0067] (1) catalyzing chenodeoxycholic acid through 7α-steroid dehydrogenase, the addition amount is 0.05% of the volume of chenodeoxycholic acid, and the catalysis temperature is 20°C to obtain the catalytic product A;

[0068] (2) The catalytic product A obtained in step (1) is filtered through a microfiltration membrane (the microfiltration membrane is a ceramic membrane, the filtration accuracy is 200nm, the filtration temperature is 20°C, and the filtration pressure is 0.2MPa), to obtain bile acid permeate;

[0069] (3) Add 7β-steroid dehydrogenase to the permeated liquid containing 7-ketolithocholic acid obtained in step (2), in an amount of 0.05% of the volume of the permeated liquid containing 7-ketolithocholic acid, The catalytic temperature is 20°C, and the catalytic reaction is carried out to obtain the catalytic product B;

[0070] (4) The catalytic product B obtained i...

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Abstract

The invention discloses a production process of ursodeoxycholic acid. The production process includes using the chenodeoxycholic acid as a substrate, conducting catalytic reaction through 7alpha-hydroxysteroid dehydrogenase and / or thallus containing the 7alpha-hydroxysteroid dehydrogenase; filtering an obtained product through a ceramic membrane to remove zymoprotein or the thallus to obtain 7-ketolithocholic acid; using the obtained 7-ketolithocholic acid as a substrate to conduct catalytic reaction with the7beta-hydroxysteroid dehydrogenase and / or thallus containing the 7beta-hydroxysteroiddehydrogenase; filtering an obtained product with the ceramic membrane to remove the zymoprotein or the thallus to obtain crude ursodeoxycholic acid, making the crude product to pass through an ultrafiltration membrane to remove small molecular protein impurities to obtain an ursodeoxycholic acid ultrafiltration membrane clear solution and then conducting nanofiltration membrane concentration, resin discoloration, concentration and drying. Compared with the prior art, the production process can improve the quality and the yield of the ursodeoxycholic acid and reduce the production cost.

Description

technical field [0001] The invention belongs to the field of chemistry, and in particular relates to a production process of ursodeoxycholic acid. Background technique [0002] Ursodeoxycholic acid, the main component is 3a, 7β-dihydroxy-5β-cholestane-24-acid, an organic compound, odorless, bitter, soluble in ethanol, insoluble in chloroform; in glacial acetic acid Soluble, dissolved in sodium hydroxide test solution. It is used in medicine to increase the secretion of bile acid, change the composition of bile, reduce cholesterol and cholesterol lipid in bile, and help the cholesterol in gallstones to gradually dissolve. Ursodeoxycholic acid is the main active ingredient of bear bile, a precious traditional Chinese medicine. It is classified as a gallstone-dissolving drug in the second edition of the Chinese Pharmacopoeia. For liver and gallbladder diseases, tablets are commonly used. [0003] Ursodeoxycholic acid is a kind of animal bile acids. Other common bile acids in...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P33/02C07J9/00
Inventor 陈磊刘怀红张南南李国学方威
Owner 南京久安源环保科技有限公司
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