| Tanreqing injection is composed of Scutellariae Radix, bear bile powder, Caprae Hircus Cornu, Lonicerae Japonicae Flos and Forsythiae Fructus. Bear bile powder is derived from Selenaretos thibetanus Cuvier by surgical drainage from the bears'gall bladder, and is used to clear heat and toxin, cool blood and suppress hyperactive liver, promote bile flow and improve eyesight in clinic.The current study aims to improve the recovery of bear bile powder extraction and the quality instability of the main constituents of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA), as well as decrease the time of production cycle and the energy consumption. The hydrolysis time of bear bile powder and the method of dehydration and crystallization for the crud extraction were investigated. Lastly,14 h was selected as the optimum hydrolysis time and the protocol of dehydration before ethyl acetate reflux was selected for crystallization. This method is proposed as an effective and reliable process for increasing the recovery of bear bile powder extraction and improving the quality standard of bear bile powder along with its extraction.The main contents were divided into three sections as follows:(1) The concentrations of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), UDCA and CDCA in hydrolysate after Oh,2h,4h,6h,8h, 10h,12h,14h,16h, 18h and 20h were firstly determinated. And 14 h was found to be more suitable compared with former hydrolysis time for 20 h. The hydrolysis time was shortened by 6 h. Moreover, the sequence of dehydration for the crud extraction, ethyl acetate reflux and the procedure of ethyl acetate recovery were also investigated. The suitable production processes were shown as follows:10% anhydrous sodium sulfate was mixed well with crud extraction, and added ethyl acetate to reflux for once in hour (totally three times). Finally, ethyl acetate solution was evaporated to twice quantity of crud extraction. As a result, the yield of the extraction was increased from 14.98% to 21.21%, and the content of UDCA was increased from 68.01% to 78.86%. However, the content of CDCA was decreased from 21.47% to 12.47%.(2) The fingerprint of bear bile powder and the determination method of TCDCA were also developed to improve the quality standard of bear bile powder and its extraction. Consequently, the TCDCA content was no less than 20.0%, and the similarity of fingerprint was no less than 95%. In addition, the fingerprint and safety evaluation for bear bile powder extraction were also added by the assay of qualitative and quantitative analysis. The UDCA content was no less than 75.0%, as the CDCA content was no more than 15.0%. The similarity of fingerprint was no less than 95%. Heavy metal concentration was less than 10 ppm, and arsenic salt was less than 2 ppm.(3) The transfer rate was also examined to further explore the transfer regulation of UDCA and CDCA in preparation processes. The transfer rate of UDCA was increased 27.48% during the extraction preparation, and the rate from bear bile powder to Tanreqing injection was enhanced 26.41% after technology optimization. Nevertheless, the transfer rates of CDCA in extraction and Tanreqing injection were decreased 5.9% and 5.8%, respectively. And in Tanreqing injection, the content of UDCA was increased from 3.62 mg/mL to 5.52 mg/mL, as the CDCA was decreased from 1.17 mg/mL to 0.78 mg/mL.The present production processes have the advantages of faster, more operable, and the improvement of yield for extraction to a maximum extent, as well as the content of UDCA, except for the control content of CDCA. Meanwhile, it proved to be effective for dominating the production processes and the quality of injection. |
PDF Full Text Request