Studies On Panax Notosinseng And Its Digital Pharmaceutical Technology

The industry of traditional Chinese medicine(TCM)is an essential part of the Chinese pharmaceutical industry.Currently,the biggest bottleneck of TCM pharmaceutical industry is the low quality standard for Chinese patent medicine,and the development of novel quality control strategy for TCM manufacturing process is the key to address this problem.Accordingly,the application of innovative approaches by the integration of multidisciplinary techniques to construct analysis methodology for TCM pharmaceutical process and related digital pharmaceutical technologies is an important problem to research.Solving it is not only meaningful for the pharmaceutical industries but also significant to academic research.TCM injections are a large variety of medicine endemic to China.Due to the technical limitations of the original research period,the quality consistency of TCM injections is still not so satisfactory.It is urgent to perform modern scientific researches to boost TCM pharmaceutical technology upgrading.Based on the technology of pharmaceutical analysis,pharmaceutical engineering,pharmaceutical informatics,and systems engineering,this paper developed a novel manufacturing process quality control methodology for Panax notoginseng injection.The main contents and gains of this dissertation are summarized as follows:1.190 batches of Panax notoginseng with different origins,plant parts and specifications were analyzed by quantitative chromatographic fingerprinting method.The difference between two plant parts of Panax notoginseng is significant,while the other characters of Panax notoginseng did not make difference.With the aid of PLS-DA and LC-MS,12 differential constituents between main roots and rhizomes of Panax notoginseng were identified,which can be employed for the confirmation of different parts of Panax notoginseng.We also proposed a multivariate statistical method for quality evaluation of Panax notoginseng based on the information of chromatographic fingerprint.The new method combines the merits of two main methods used for TCM quality control.It can be used to evaluate the quality consistency of Panax notoginseng.2.According to the characteristics of TCM manufacturing process system,a methodology for analyzing TCM manufacturing process based on the concept of'stream' was proposed.TCM pharmaceutical process can be considered as a nonlinear complex system,which is composed of the stream of material,the stream of energy,the stream of data,the stream of information,and the stream of control.The manufacturing process of Panax notoginseng injection was investigated.Critical procedures during this process were confirmed by analyzing the stream of material.The result indicated that the extraction and chromatography processes were two critical steps in the whole manufacturing process and should be paid more attention to in the follow-up applied research of digital pharmaceutical manufacturing technology.3.A digital pharmaceutical manufacturing system for regulating the extraction process of Panax notoginseng was established.Firstly,by extending the representativeness of samples and adding the index component,the accuracy and application domain of NIR method were enhanced.The parameters of extraction process including temperature,time,solvent consumption and particle size were systematically evaluated based on their influence on five saponins(notoginsenoside Ri,ginsenoside Rgi,Re,Rbi and Rd)in the extraction.A BP-ANN model was established by PSO optimization and cross-validation.By rapid determination of herb contents with NIR method,we can adjust the extraction process parameters in advance to achieve quantitative extraction,which is very meaningful for ensuring the consistency of drug quality.Finally,a multi-objective optimization method for TCM manufacturing process was established,which uses the Pareto method to calculate a series non-inferior condition for extraction.When distill with 7.75 times of solvent and 100 min distill time,the extraction solution fulfilled the quality requirements at minimum cost.4.A digital pharmaceutical manufacturing system for regulating the column chromatography process of Panax notoginseng injection was established.The elution curves of five saponins(notoginsenoside R1,ginsenoside Rg1,Re,Rb1 and Rd)under different solvent,velocity,and volume were examined to establish a fitting model by BP network.By using the model,the influence of process parameters was evaluated and optimized.On the premise of meeting quality requirements,the cost was decreased to the lowest when the elution solvent of 70%ethanol,the elution rate of 0.5 BV/h,the elution bed volume of 0.8.5.Taking the manufacturing process of Panax notoginseng injection as an example,the method of constructing TCM digital pharmaceutical manufacturing system was proposed.Moreover,the related technological means for digitalization procedure,modeling procedure,and quantification procedure of TCM digital pharmaceutical manufacturing system were introduced in brief.