Optimization Of Synthesis Craft And Study Of Quality Specification Of Verticinone-cholic Acid Salt

The Shedan-Chuanbei Powder, which has established satisfactory activities of eliminating phlegm, relieving cough and asthma, is a traditional complex prescription . Bile acids from Shedan and Verticinone from Fritillariae. Cirrhosae are the main constituents of it .According to the view of"combination principle"in pharmaceutical chemistry, Verticinone-cholic Acid Salt was synthesized through ionic bone effect from verticinone and cholic acid , which had stronger antitussive activity and lower toxicity than verticinone. It will be a hopeful drug with great potential once its potence is proved in clinic .In this study ,we are trying to optimize the synthesis craft of the Verticinone-cholic Acid Salt .Besides, the physico-chemical properties of the Verticinone-cholic Acid Salt will be described in order to set a reasonable quality specification .In the synthesis craft optimization test ,it was found that using ethanol or acetone as a reaction medium would lead to the same result . According to results of the orthogonal experiment, the three factors including reaction time ,reaction temprature and proportion ratio of reaction medium caused no apparente influence on the reaction yield . Almost the same reaction yield was obtained after six hours. So we suggest using ethanol or acetone to replace THF as reaction medium in the work afterward . And the reaction time may be shortened to twelve hours . The reaction medium is enough when all the starting materials are dissloved completely .The physico-chemical properties of the Verticinone-cholic Acid Salt have been studied systematically based on the ChP .And the results are helpful to set methods for identification and qualitification .The IR data of the Verticinone-cholic Acid Salt is quite different from that of the mixture of Verticinone and cholic Acid .So IR data proved first and foremost to identify the Verticinone-cholic Acid Salt .Other parameters ,such as melting point, rotation, value of pH et al will also be demonstrative for identification. As the result of no apparente UV absorption , Colorimetric method and HPLC-ELSD method are preferred for the quantitation . These methods were tested and verified . Both of them are fit for the assay ,however, the HPLC-ELSD method seemed to be more accurate as its recovery was about 99% ,while, that of the colorimetric method is only about 96% .The stability test was carried out on the basis of the ChP . Results of the factors affecting test showed that the Verticinone-cholic Acid Salt was quite stable in light and heat. But it might be unstable as its weight increased after 10 days when put in the high humidity environment.Meanwhile, it would be hydrolyzed by acid, base or undergo oxidation when oxidants were introduced . During the accelerated test we found that agglomerate appeared in one of the three samples after three months .And all of the three samples became agglomerate after six months . However, TLC and HPLC detection showed no appearance of new compound .