The Extraction Of Chenodeoxycholic Acid From Duck Bile Paste And The Synthesis Of Ursodeoxycholic Acid

Chenodeoxycholic acid(CDCA)exists in the bile of chicken,duck,pig and so on.CDCA is commonly used in clinical for the treatment of liver and gallbladder diseases.Ursodeoxycholic acid(UDCA)is the most used drug in the clinical for the treatment of cholesterol gallstone disease,while CDCA is the raw material for the synthesis of UDCA.Chenodeoxycholic acid is mainly extracted from chicken bile.As the increasing market demand of chenodeoxycholic acid,the producers seize the raw material market,leading to the rising price of chicken bile.In order to reduce cost,many producers hope that through technology innovation to realize the production of chenodeoxycholic acid from duck or pig bile.UDCA can be used to treat all kinds of cholelithiasis diseases,especially for cholelithiasis.It is a kind of drug with extensive effect and good clinical effect.The traditional method of extracting UDCA from bear bile is limited and is contrary to animal protection,so it is of great significance to synthesize UDCA by chemical synthesis.There were mainly three aspects in this paper:the method of extracing chenodeoxycholic acid from duck bile paste;the method of purifying CDCA crude;the synthesis method of UDCA.Specific work and achievements are as follows:Crystallization method was used to extract chenodeoxycholic acid from duck bile paste.The five factors of crystallization solvent,liquid-solid ratio(V/W),extraction time,extraction temperature and concentration ratio of concentrated liquid(V/W)were studied.The optimal extraction conditions were obtained by single factor and response surface experiments,just as follows:ethyl acetate was extracted as solvent,the ratio of liquid to solid was 8,the temperature was 78 ?,the time was 1 h,and the concentration ratio was 3.5.The extraction rate of CDCA was 80.2%.Purify the extracted crude,the four factors of the type of recrystallized solvent,the amount of the recrystallized solvent,the concentration of concentration liquid(V/W)and the recrystallization temperature were studied.The optimum purification conditions were obtained through the single factor and response surface experiment,just as follows:ethyl acetate is a recrystallized solvent,the ratio of liquid-solid ratio is 12,the concentration ratio is 3,the recrystallization temperature is 0 ?,and the comprehensive value of CDCA purification is 76.5%under this condition.1HNMR and IR confirmed the product obtained was CDCA.The product melting point was 168.5 ?-169.5 ?,the rotation 11.25°.HPLC determined the purity of CDCA was 98.1%.Synthesis of UDCA with CDCA as raw material,the five factors of NBS addition,acetone and water ratio,KBH4 addition,reaction time and ethanol addition were studied.The optimum synthesis and purification conditions are obtained by single factor experiment,just as follows:the molar ratio of NBS to CDCAis 1.2,acetone:water =3:1,the molar ratio of KBH4 to 7-keto cholic acid is 3.5,the time was 3 h,the ratio of solid to liquid is 1:8.Under this condition,the yield of UDCA is 71.2%relative to CDCA.The structures of the synthesized products were characterized by IR and 1HNMR.The product melting point was 204.5 ?-205.5 ?,the rotation 59.7°.HPLC determined the purity of UDCA was 97.9%.