Studies On Quality Control Methods For Chinese Medicinal Materials And Manufacturing Process Based On Real Time Release Testing

The ingredients of traditional Chinese medicine(TCM)are complex as well as various.Therefore,the quality control of TCM has been one of the main bottlenecks in the development of TCM industry for a long period.In recent years,process analytical technology(PAT)has played a significant advantage in the quality control of TCM.Real time release testing(RTRT)is one of the important concepts of PAT.Near infrared spectroscopy(NIR)and statistical process control(SPC)are two frequently used PAT tools,which are suitable for RTRT of Chinese medicinal meterials and manufacturing process of TCM to improve the quality control level.In this thesis,Ginkgo biloba leaves,extraction process of Yangxinshi Pian(YXSP),and concentration process of Lonicerae Japonicae Flos.were selected as the research objects.RTRT was attempted to be applied to quality control of Chinese medicinal materials,extraction and concentration of TCM manufacturing process.The main researches and achievments are as follows:(1)RTRT was applied to the quality control of Ginkgo bilba leaves with NIR as a tool.Rapid determination models for flavonoids glycosides(FG),moisture and extractum content were established by NIR combined with chemometrics.The results indicated that relative standard errors of prediction(RSEP)was within 10%.And a discriminant analysis(DA)model was used for qualitative quality analysis of Ginkgo biloba leaves.The accuracy of DA model was more than 90%.According to regulations of Chinese pharmacopoeia and Mahalanobis distance values,the accuracy of RTRT was 86.7%by NIR,which satisfied the requirement of practical manufacturing.(2)RTRT was applied to the quality control of YXSP extraction process.NIR was used to establish quantitative analysis models of puerarin,salvianolic acid B,epimedium glucoside and solube solid content of YXSP extraction solution in real time.SPC control model was established based on data collected in manufacturing process.Shewhart limit was used as quantitative control limit and D statistics and Q statistics limits were used as qualitative control limit.The results suggested that the combination of the three SPC control charts was able to discriminate normal batches from abnormal batches.RTRT based on NIR and SPC could improve the quality control level of YXSP extraction process.(3)RTRT was applied to the quality control of Lonicerae Japonicae Flos.concentration process with NIR and SPC as PAT tools.NIR models were established for real time analysis of neochlorogenic acid(NCA),chlorogenic acid(CA),4-Dicaffeoylquinic Acid(DCA),density and soluble solid content.The results showed that the prediction ability of the models for 5 indicators were satisfactory.Meanwhile,Shewhart chart,D statistics chart and Q statistics chart were established.The control limits were used as the criteria of RTRT,which could discriminate normal batches from abnormal batches.The accuracy of RTRT was 100%.Batches that conform to release criteria were permitted to be released to subsequent unit operations.