CN103044512A

CN103044512A - Method for refining chenodeoxycholic acid crude product

Info

Publication number: CN103044512A
Application number: CN2012105551853A
Authority: CN
Inventors: 梁万超; 吴眉平; 刘建英
Original assignee: SICHUAN DAXIONG BIOTECHNOLOGY CO Ltd
Current assignee: SICHUAN DAXIONG BIOTECHNOLOGY CO Ltd
Priority date: 2012-12-19
Filing date: 2012-12-19
Publication date: 2013-04-17

Abstract

The invention discloses a method for refining a chenodeoxycholic acid crude product. The method comprises the following steps: dissolving the chenodeoxycholic acid crude product with 5-10 times of solvent, heating and flowing back for 2 hours, and filtering; cooling filtrate to 0-5 DEG C under stirring, and keeping stirring crystallizing for 2 hours; and filtering, washing with 0-5 DEG C of solvent being 2 times of the chenodeoxycholic acid crude product, and drying to obtain a finished product. The refining method has the following beneficial effects: (1) after the chenodeoxycholic acid crude product is dissolved at high temperature with the solvent, the chenodeoxycholic acid crude product is crystallized at low temperature to remove bile acid impurities, the properties of the solvent in the heating process is stable, the quality of chenodeoxycholic acid cannot be influenced, the purity of the obtained chenodeoxycholic acid is over 96 percent, the bile acid is below 2 percent, ad the yield is over 80 percent; (2) only one kind of solvent is used in the method, the dosage of the solvent is small, and the cost is low; (3) the operation steps of the method are simple, and the conditions of all steps are easy to control; and (4) the production cycle of the method is 4-6 hours, the production cycle is short, the economic benefit can be increased, and the method is suitable for mass production.

Description

The process for purification of CDCA acid crude

Technical field

The present invention relates to a kind of process for purification of CDCA acid crude, being 85 ~ 90% CDCA acid crude with purity particularly obtains highly purified Chenodiol by solvent recrystallization is refining.

Background technology

The Chenodiol of selling on the market now mainly is to extract gained from family's livestock bile, wherein major impurity is cholic acid, its purity of Chenodiol of explained hereafter is 85 ~ 90% now, impurity cholic acid content is 4 ~ 5%, to affect its yield and purity for synthetic ursodesoxycholic acid, in order addressing this problem, Chenodiol to be made with extra care, its purity is reached more than 96%, and cholic acid is below 2%.

A kind of process for purification of CDCA acid crude, application number are 02128138, behind the employing acetic acid ethyl dissolution CDCA acid crude, add cholic acid and other hydrophilic impurities in the weak ammonia extraction Chenodiol ethyl acetate solution, get the Chenodiol finished product.But the ethyl acetate character of using in this method is unstable, is heated and easily decomposes, and affects the quality of Chenodiol, and operation controllability is poor, is unsuitable for scale operation.

Be the production method that 86% Chenodiol is produced ursodesoxycholic acid with content, application number is 200810010076.7, use first methyl alcohol heating for dissolving CDCA acid crude in the method, dissolution time is 3-7h, add again bromine liquid, reaction times is 6-10h, and this process is to obtain the higher Chenodiol of purity for the production of ursodesoxycholic acid.By adding bromine liquid the cholic acid redox of Chenodiol is become Chenodiol among the present invention, but operation steps of the present invention is complicated, the production cycle is long, the cost height, and reaction process is wayward, and inapplicable in the production.

Summary of the invention

For the above-mentioned technical problem that prior art exists, the invention provides a kind of process for purification of CDCA acid crude, present method operation steps is simple, operation is easy to control, and solvent load is few, and is with short production cycle, the Chenodiol purity of gained is more than 96%, and cholic acid is below 2%.

The present invention takes following technical scheme:

A kind of process for purification of CDCA acid crude may further comprise the steps:

1) get the CDCA acid crude, with the dissolution with solvents that 5-10 doubly measures, reflux 2h filters; To guarantee that the CDCA acid crude is dissolved in the solvent fully.

2) filtrate under agitation cools to 0～5 ℃, keeps stirred crystallization 2h.

3) filter, with the solvent wash of 0 ~ 5 ℃ of 2 times of amount of CDCA acid crude, to guarantee that drying obtains finished product with the impurity washes clean of plane of crystal.

As optimal way of the present invention, in the method, described solvent is a kind of in chloroform, methylene dichloride, the acetonitrile.

As optimal way of the present invention, in the method, the temperature of step 3) drying is 60-65 ℃.

The invention has the beneficial effects as follows: after 1) present method adopted the solvent high-temperature digestion, low temperature crystallization was removed cholic acid impurity, and solvent is stable in properties in heat-processed, can not affect the quality of Chenodiol, the Chenodiol purity of gained is more than 96%, and cholic acid is below 2%, and yield is more than 80%; 2) only use a kind of solvent in present method, and solvent load is little, cost is low; 3) present method operation steps is simple, and the condition of each step is easy to control; 4) production cycle of present method is 4-6h, and is with short production cycle, can increase economic efficiency, and is suitable for scale operation.

Embodiment

Embodiment 1:

Step 1): get CDCA acid crude 50g, its purity is 88%, and cholic acid content is 4.3%, is dissolved in the 500mL chloroform, and reflux 2h filters.

Step 2): filtrate cools to 0 ~ 5 ℃, keeps stirred crystallization 2 hours.

Step 3): filter the chloroform washing crystal that usefulness 100mL is 0 ~ 5 ℃ 2 to 3 times, 60-65 ℃ of dry finished product 40.5g that gets in the hot-air oven.

Yield 81%, CDCA acid content 96%, cholic acid 2%.

Embodiment 2:

Step 1): get CDCA acid crude 50g, its purity is 88%, and cholic acid 4.3% is dissolved in the 500mL methylene dichloride, and reflux 2h filters.

Step 2): filtrate cools to 0 ~ 5 ℃, keeps stirred crystallization 2 hours.

Step 3): filter the washed with dichloromethane that usefulness 100mL is 0 ~ 5 ℃ 2 to 3 times, 60-65 ℃ of dry finished product 40g that gets in the hot-air oven.

Yield 80%, CDCA acid content 97%, cholic acid 1.8%.

Embodiment 3:

Step 1): get CDCA acid crude 50g, its purity is 88%, and cholic acid 4.3% is dissolved in the 250mL acetonitrile, and reflux 2h filters.

Step 2): filtrate cools to 0 ~ 5 ℃, keeps stirred crystallization 2 hours.

Step 3): filter, use the acetonitrile of 0 ~ 5 ℃ of 100mL to wash 2 to 3 times, 60-65 ℃ of dry finished product 40.2g that gets in the hot-air oven.

Yield 80.4%, CDCA acid content 97%, cholic acid 1.9%.

Although invention has been described with reference to explanatory embodiment of the present invention here, above-described embodiment only is the better embodiment of the present invention, embodiments of the present invention are not restricted to the described embodiments, should be appreciated that, those skilled in the art can design a lot of other modification and embodiments, and these are revised and embodiment will drop within the disclosed principle scope and spirit of the application.

Claims

1. the process for purification of a CDCA acid crude is characterized in that may further comprise the steps:

1) get the CDCA acid crude, with the dissolution with solvents that 5-10 doubly measures, reflux 2h filters;

2) filtrate under agitation cools to 0～5 ℃, keeps stirred crystallization 2h;

3) filter, with the solvent wash of 0 ~ 5 ℃ of 2 times of amount of CDCA acid crude, drying obtains finished product.

2. the process for purification of CDCA acid crude according to claim 1 is characterized in that described solvent is a kind of in chloroform, methylene dichloride, the acetonitrile.

3. the process for purification of CDCA acid crude according to claim 1, the temperature that it is characterized in that the step 3) drying is 60-65 ℃.