Method for synthesizing ursodesoxycholic acid and tauroursodeoxycholic acid from swine bile

Abstract

The invention relates to a method for synthesizing ursodesoxycholic acid and tauroursodeoxycholic acid from swine bile. The method comprises the following steps: extracting mixed cholic acid, separating the mixed cholic acid and synthesizing the ursodesoxycholic acid and the tauroursodeoxycholic acid; the method is characterized by utilizing the swine bile as a raw material, and carrying out front-end impurity removing by adopting enzymolysis, ultrafiltration and nanofiltration methods, thus extracting the mixed cholic acid; separating the extracted mixed cholic acid; then synthesizing the ursodesoxycholic acid and the tauroursodeoxycholic acid. By adopting the method disclosed by the invention, the raw material is wide and easy to obtain, the purity of the tauroursodeoxycholic acid is high, the conversion rate is high, the repeatability is good, the cost is lower, the operation is simple, the preparation technology is simple, environment friendliness is realized, the method is more suitable for industrial production and is beneficial for saving resources and reducing energy consumption, economic benefit and environmental benefit are obvious, and sustainable development of an industry can be promoted.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and relates to a preparation method of tauroursodeoxycholic acid, in particular to a method for synthesizing ursodeoxycholic acid and tauroursodeoxycholic acid from pig bile. Background technique [0002] Bile is a product continuously secreted by human or vertebrate liver cells. It is a viscous, colored alkaline liquid with a bitter taste. Its components include bile acid, bile salt and bile pigment in addition to water, and a small amount of cholesterol. , fatty acids, lecithin, electrolytes and proteins. The more common animal bile today is generally poultry bile, pig bile, ox bile, bear bile, snake bile and so on. Bile acid is the main component of bile, accounting for about 50-70% of the total amount of bile. The physiological function of bile is mainly exerted by bile acid. When used as a medicine, bile acid can be used for antipyretic, antispasmodic and antitussive, regulating Blood p...

AI Technical Summary

Problems solved by technology

For example, the patent CN102453071A has reported the preparation method of directly extracting and synthesizing chenodeoxycholic acid and ursodeoxycholic acid from pig bile paste or leftovers. The problem is that hyodeoxycholic acid is not extracted, and its properties are similar to those of ursodeoxycholic acid. Oxycholic acid is similar, which not only reduces the added value, but also increases the steric hindrance effect of subsequent reactions; bromine water oxidation reaction is strong, difficult to control, and has many side reactions, such as peroxide 3,7-diketone gallstone acid, if it reduces the conversion rate and increases impurities; since metal sodium and potassium are active metals, the hydrogenation reaction is strong, not only difficult to control, but also has potential safety hazards, and must be preserved in paraffin or kerosene; the purification process is insufficient, only Impurities such as hyodeoxycholic acid, incompletely reacted chenodeoxycholic acid, and over-reacted 3,7-diketolithocholic acid derivatives cannot be removed by one-step acidification precipitation

For example, the patent CN102477059A reports a high-purity tauroursodeoxycholic acid and its preparation method. The existing problem is that the synthesized mixed acid anhydride is unstable, easy to decompose when exposed to water, and easy to racemize when exposed to heat, so the conversion rate is relatively low. , and the low temperature reaction conditions are difficult to control; at the same time, triethylamine and ethyl chloroformate in the raw materials used have certain toxicity, and their residues are easy to adsorb and embed in the crude crystals. Because they are insoluble in water, it is difficult to wash them out with water.