The Quality Control Technique Research Of Danshen Extraction And Danshen Precipitation

The manufacturing procedure of Danshen Injection belongs to classical batch operation. The quality variance of danshen raw material among batches and the manufacturating process flucation will influence the quality stability of process intermediates and then the quality of final products. "Quality cannot be tested into products, it should be built-in or should be by design." In order to improve Danshen Injection's quality, the relationship among raw material, the process parameters and quality control indexes in the process should be explored, and the methods to directly adjust and optimize the intermediates' quality in the unit operations of manufacturing procedure should be researched. Danshen extract is the initial intermediate of the whole manufacturing procedure and danshen ethanol precipitation is a critical unit operation in Danshen Injection's manufacturing procedure to separate the impurity and active components. Thus, the two unit operations, which are extraction and ethanol precipitation in Danshen Injection manufacturing procedure, were selectd to be the research objects of this thesis. To danshen extracting operation, the influence of process variables to the extracting results and the relationship of quality indexes were studied. To danshen ethanol precipitating operation, the research about the relationship among raw material, the process parameters and quality control indexes was performed. The main research content of this thesis includes:1. Box Behnken experimental design was applied to invesgate the relationship between the process variables, including first extracting time, second extracting time, the first extracting temperature, the second extracting temperature, and the quality indexes of the extracting operation, which are active component, pH value, the sugar content and the solvable solid content of extract. NIR models for quickly measuring the content of danshensu, protocatechualdehyde, the sugar content and the solvable solid content were developed to help realize the purpose of quick quality evaluation of danshen extract.2. Box Behnken experimental design with blocks was implemented to investigate the influence of the factors (the precipitation temperature, 75 % ethanol volume to be added, 95 % ethanol volume to be added and the density of danshen concentrated solution) on ethanol precipitating liquid volume and the loss rate of active components such as danshensu, protocatechualdehyde, caffeic acid, salvianolic acid D and salvianolic acid B. Through collecting NIR spectra of danshen ethanol precipitating liquid, active content prediction models were developed. The effects of process variables's changing on operation results were also well analyzed based on the NIR spectra data. The regression models for dashen ethanol precipitation to predict the final ethanol volume, the loss rate of danshensu, the loss rate of salvianolic acid D and the loss rate of salvianolic acid B were alos developed.3. An active component recovery prediction method for danshen ethanol precipitating operation in the plant was proposed by analyzing and modeling the operation data in field. The models testified that, under the manufacturing scale, it was possible to realize the precise result prediction of danshen ethanol precipitation by developing regression models which fused the quality indexes of danshen concentrated solution with process variables togather. The developed models could be used for manufacturing guide at field.