Studies On Monitoring And Control Method Of Radix Salviae Miltiorrhizae Extraction Process Based On Data-driven And Mechanism Modeling

Extraction process is the key unit operation in the pharmaceutical process of traditional Chinese medicine.The quality of the extract directly affects the quality of the final product.Therefore,the implementation of process monitoring during the production process to ensure the quality of the extract is of great significance to improve the quality of traditional Chinese medicine products.This study took Radix Salviae miltiorrhizae as the research object,the kinetic model and rapid quantitative model of Radix Salviae miltiorrhizae extraction process were established based on the mass transfer law of natural product,the degradation law of salvianolic acid,design of experiment(Do E)and process analytical technology(PAT).At the same time,a program for monitoring Radix Salviae miltiorrhizae extraction process was developed,which realized real-time monitoring and control of Radix Salviae miltiorrhizae extraction process.The main content and academic results of this research are as follows:1.The kinetics of Radix Salviae miltiorrhizae extraction process were preliminary studied.The mass transfer model was established based on Fick’s first diffusion law,partition equilibrium,internal mass transfer and external mass transfer.Meanwhile,the mass transfer model was further combined with the degradation model of salvianolic acid,and the extraction kinetics model of Salvianolic acid B(SAB),Lithospermic acid(LA)and Danshensu(DSS)was established.According to the sensitivity analysis results,the relative prediction error is within 5%,indicating that the model has good predictive performance.In addition,the influence of solvent-to-solid ratio,stirring,and temperature on the mass transfer and degradation of phenolic acid were investigated.2.A data-driven combined with mechanical method was used to establish the extraction kinetic model of five components: SAB,Salvianolic acid E(SAE),LA,Salvianolic acid A(SAA)and DSS.First,on the basis of the above research,the extraction mechanism model was optimized;then,the quantitative relationship among temperature,p H,nitrogen flow rate and the extraction kinetic parameters of salvianolic acid was investigated through response surface method;finally,the result of response surface method was further optimized and the extraction kinetic model was established.Model validation showed that the predicted value was close to the measured value,indicating that the model could predict the change rule of phenolic acids in Radix Salviae miltiorrhizae extraction process.3.Using hierarchical multivariate analysis method combined with near infrared(NIR)and process parameters to establish a rapid quantitative model of phenolic acids in Radix Salviae miltiorrhizae extraction process.Principal component analysis(PCA)was used to reduce the dimension of NIR data and increase the weight of process parameters.Support vector regression(SVR)was used to establish process parameters,principal component scores,and phenolic acids content non-linear quantitative relationship.Compared with the traditional Partial least squares(PLS)method,the influence of process parameter changes on the prediction performance of the model was effectively reduced,and the established model had better stability and predictive performance.4.Based on Labview,a Radix Salviae miltiorrhizae extraction process monitoring system was developed,which could be used for fitting the extraction kinetic model,training the fast quantitative model and real-time monitoring and controlling.Finally,a quality consistency control strategy for Radix Salviae miltiorrhizae extraction process was proposed.