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Preparation method of deoxycholic acid

A technology of deoxycholic acid and cholic acid, which is applied in the fields of steroids, fermentation, organic chemistry, etc., can solve the problems of increasing the risk of high-temperature reactions, high requirements for the purity of cholic acid, and unsuitability for industrial production, so as to increase the total income efficiency and solvent utilization, good specificity and high specificity

Pending Publication Date: 2022-04-19
四川澄华生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Existing synthetic methods have higher requirements on the purity of the raw material cholic acid, resulting in greatly increased production costs, large consumption of sodium hydroxide and hydrazine hydrate in the process of carrying out the Huangminglong reaction, greatly increasing the risk of high-temperature reactions, and the total The yield is not high, and the whole process is complicated, causing great environmental pollution and not suitable for industrial production

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  • Preparation method of deoxycholic acid

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Embodiment 1

[0026] A preparation method of deoxycholic acid, specifically comprising the following steps:

[0027] S11. Dissolving 250 g of the cholic acid (40% content, containing 100.0 g of pure cholic acid, 244.75 mmol) with 200.0 g of 5% aqueous sodium hydroxide solution (250 mmol) to obtain a solution;

[0028] S12. Add dropwise the lysate to 2500ml of the 7-position oxidase culture solution (the oxidase concentration is 30U / ml) to carry out reaction conversion. During conversion, the temperature is controlled at 25°C, the pH is controlled at 8.3, and the solution is controlled at 8.3. The oxygen content is not less than 30%;

[0029] S13. Terminate the reaction after the reaction reaches a conversion rate of >99%, filter the converted mixture, raise the temperature of the filtrate to 40° C., then adjust the pH to 3 with 15% sulfuric acid at a temperature of 40° C., and stir and crystallize at the same time. Thereafter, the pH-adjusted mixture was stirred and grown at 50°C for 3 hou...

Embodiment 2

[0035] A preparation method of deoxycholic acid, specifically comprising the following steps:

[0036] S11. Dissolving 250 g of the cholic acid (40% content, containing 100.0 g of pure cholic acid, 244.75 mmol) with 200.0 g of 5% aqueous sodium hydroxide solution (250 mmol) to obtain a solution;

[0037] S12. Add the solution dropwise to 2500ml of 7-position oxidase culture solution to perform reaction conversion (the concentration of the oxidase is 40U / ml). During the conversion, the temperature is controlled at 27°C, the pH is controlled at 8.5, and the dissolved The oxygen content is not less than 30%;

[0038] S13. Terminate the reaction after the reaction reaches a conversion rate >99%, filter the converted mixture, raise the temperature of the filtrate to 45° C., then adjust the pH to 4 with 15% sulfuric acid at a temperature of 45° C., and stir and crystallize at the same time. Thereafter, the pH-adjusted mixture was stirred and grown at 57°C for 4 hours, and then filt...

Embodiment 3

[0044] A preparation method of deoxycholic acid, specifically comprising the following steps:

[0045] S11. Dissolving 250 g of the cholic acid (40% content, containing 100.0 g of pure cholic acid, 244.75 mmol) with 200.0 g of 5% aqueous sodium hydroxide solution (250 mmol) to obtain a solution;

[0046] S12. Add the solution dropwise to 2500ml of 7-position oxidase culture solution to perform reaction transformation (the concentration of the oxidase is 50U / ml). During the transformation, the temperature is controlled at 30°C, the pH is controlled at 8.6, and the solution The oxygen content is not less than 30%;

[0047] S13. Terminate the reaction after the reaction reaches a conversion rate of >99%, filter the converted mixture, raise the temperature of the filtrate to 50° C., then adjust the pH to 4 with 15% sulfuric acid at a temperature of 50° C., and stir and crystallize at the same time. Thereafter, the pH-adjusted mixture was stirred and grown at 55°C for 4 hours, the...

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Abstract

The invention discloses a preparation method of deoxycholic acid, which comprises the following steps: by taking cholic acid with the purity of more than 35% as a raw material, oxidizing the cholic acid through oxidase to obtain 7-ketocholic acid; then carrying out Huang Minglong reaction on the 7-ketocholic acid to obtain a deoxycholic acid crude product; purifying the crude oxycholic acid product to obtain deoxycholic acid; according to the invention, special 7-site specific oxidase is selected to oxidize the 7 site, so that specificity and specificity are realized, and the oxidation effect of the 7-hydroxyl site is greatly improved; in the preparation process of the compound 7-ketocholic acid, the product which is easy to filter and high in content is obtained by adjusting the pH value, the crystallization temperature and the crystallization time; in the preparation of the compound deoxycholic acid, through condition optimization, the dosage of sodium hydroxide and hydrazine hydrate is reduced, the safety is improved, and the material cost is reduced; in a crude product recovery solvent crystallization process, water-soluble impurities are removed by adjusting the pH value, so that the total yield and the solvent utilization rate are improved.

Description

technical field [0001] The invention relates to the field of preparation of deoxycholic acid, in particular to a preparation method of deoxycholic acid. Background technique [0002] Deoxycholic acid mainly exists in the form of taurine and glycine in bile, and it has the effect of promoting bile secretion and anti-inflammation clinically. Deoxycholic acid is also mainly used in biochemical research, bacteriology and enzymatic research; as a lipase accelerator and anion remover, for the dissolution of proteins, and for the preparation of bacterial culture media. Deoxycholic acid can be made into various deoxycholate salts, which are mainly used in various preparations, such as tablets, injections and other dosage forms, in addition to inducing apoptosis of normal human liver cells. Deoxycholic acid can also synthesize complexes with amino acids and analogs such as taurine deoxycholic acid. Existing synthetic methods have higher requirements on the purity of the raw materia...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J9/00C12P33/06
CPCC07J9/005C12P33/06
Inventor 黄显邓治荣李波黄清东彭捷张翔
Owner 四川澄华生物科技有限公司