| Ethanol precipitation, a widely applied technology in the production of traditional Chinese medicine, is usually the key process in the manufacturing of Chinese medicine injections. The quality of ethanol precipitation affects the effects of following processes and the quality of drugs. Therefore it is urgent to investigate the mechanism of ethanol precipitation for parameter optimization and better control. In this paper, Danshen extracts and Guanxinning extracts were used as samples to investigate the transfer rule of components in ethanol precipitation processes. Mathematical models were established to describe the phenomena. The main contents and achievements of this thesis are summarized as follows:1. The effects of several process parameters, such as temperature, mass ratio of ethanol and concentrated extract (E/CE ratio), dry matter content of concentrated extract and pH value of supernatant, on the first ethanol precipitation of Guanxinning injection were investigated. The results show that low refrigeration temperature can remove more saccharides. E/CE ratio remarkably affected phenolic compounds recovery and impurity removal. The effects differed among phenolic compounds. Higher dry matter content of concentrated extract resulted in higher impurity removal but lower phenolic compounds recovery. The pH value in supernatant has little effect on saccharide removal. However, the content of some phenolic compounds such as DSS and SaB were higher as supernatant pH value lowered.2. The influences of process parameters on the phenolic compound contents in supernatant of Danshen first ethanol precipitation were investigated. The experiments of simulated systems show that the content of saccharides and mineral salt in concentrated extract had little effect on phenolic compound content in supernatant. The results of Taguchi experiments show that the effects of pH value of concentrated extract is largest, the effects of apparent ethanol content of supernatant is mediate and the effects of refrigeration temperature is relatively less. It is recommended to control pH value of concentrated extract to diminish the fluctuations of phenolic compound contents of supernatant.3. Assuming that DSS and SaB lost in ethanol precipitation because of low solubility of their salts, the pKa values of DSS and SaB were calibrated, which were3.63and3.56respectively. The solubility of DSS salt and SaB salt were also calculated, which were0.863mg/g and7.53mg/g respectively. It can be calculated that more than80%of DSS and SaB existed in supernatant in their salt form.4. Assuming the logarithm of solubility and the logarithm of water content have linear relationship and no water exist in precipitation, mathematical models between phenolic compound solubility, sccharide solubility, dry matter solubility and water content are established. The Radj2of regression equation were higher than0.98. The phenolic compounds recovery, purity, total sccharide removal and dry matter removal were calculated. The mathematics model shows satisfactory prediction.5. Studies on removal rules of saccharides in ethanol precipitation were carried out. Experimental data on the solubility of D-glucose, D-fructose and sucrose in the mixed solvents composed of water and ethanol from273.2to293.2K were determined. The results show that higher ethanol content and lower refrigeration temperature can decrease the solubility. Solubility was predicted by M-UNIQUAC, S-UNIFAC and mS-UNIFAC model. Using M-UNIQUAC model, the average absolute deviations of D-glucose, D-fructose and sucrose were0.65%,1.93%and1.85%, respectively.6. Using Danshen concentrated supernatant as the objective, studies on ethanol precipitation and liquid-liquid extraction was carried out to compare the effects on efficacy components, toxic and harmful components and other components. According to the characteristics on efficacy component purity improvement and potential toxic and harmful component removal, the liquid-liquid extraction is superior to ethanol precipitation. Therefore the combination technology of "ethanol precipitation+liquid-liquid extraction" showed more advantages in drug safety and product quality control than the combination technology of "ethanol precipitation+second ethanol precipitation"... |
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