Studies On The Quality Control Technology Of Ethanol Precipitation For Guanxinning Injection

The production of Guanxinning injection consists of extraction, concentration, ethanol precipitation, acid precipitation, alkaline precipitation and adsorption with activated carbon. Ethanol precipitation is a key operation unit in the separation of impurities and effective components. The quality of drugs will be remarkably affected by this procedure. Therefore it is urgent to investigate the quality control method for ethanol precipitation. In this thesis, Guanxinning injection was selected as the research sample. The influences of raw material and process parameters were studied. The concepts of QbD (Quality by Design) were used to guide this research. The main research content of this thesis includes:1The impacts of pH value, conductivity, total saccharide content and phenolic compound contents of the concentrated supernatant of Guanxinning first ethanol precipitation (CSFEP) were studied. Phenolic compound recoveries were considered as indicators. Stepwise regression and Partial Least Squares (PLS) regression were used to develop recovery models, the key quality indicators were important in both regression methods. The contents of Danshensu, caffeic acid and Salvianolic acid B have significant impacts on phenolic compound recoveries. Therefore the three key quality indicators should be controlled in the concentration process of CSFEP.2The influences of refrigeration temperature, the mass ratio of ethanol and concentrated supernatant (E/CS ratio) and dry matter content of concentrated supernatant (DMCCS) on the second ethanol precipitation of Guanxinning Injection were investigated. The results show that DMCCS and refrigeration temperature affected the quality of supernatant notably. Phenolic compound recoveries and dry matter removal were taken as optimization indicators to optimize the process. Under the optimized conditions of the second ethanol precipitation, dry matter removal was found to be50.0%, the recovery of Danshensu, protocatechuic aldehyde, caffeic acid, ferulic acid, rosmarinic acid, lithospermic acid and Salvianolic acid B were62.0%,89.5%,94.3%,88.5%,76.9%,54.3%and54.2%, respectively. The predicted phenolic compound purities agreed well with experimental results.3Ultraviolet (UV) spectroscopy and Near-infrared (NIR) spectroscopy of second ethanol precipitation supernatant was measured and quantitative analysis models were developed. The analysis performance of UV spectroscopy model was better than that of NIR spectroscopy. The R2of most UV spectroscopy models was more than0.97, therefore UV spectroscopy was chosen to develop models. Phenolic compound recoveries and dry matter removal were correlated with UV spectroscopy. The R2and R2adj of the8models were all more than0.96, which indicates that these models with good accuracy and predictive ability can be used for the adjustment of the process parameters.