| Objective:The controllable quality of Chinese patent medicines is the safe and effective basis for medication.The prescription of compound Danshen tablets consists of 450g of Danshen,141g of Sanqi and 8g of borneol.The function is to promote blood circulation,relieve qi and relieve pain,attending chest suffocation and angina pectoris.As a basic Chinese patent medicine for treating coronary heart disease,it is widely used in clinical practice.The Chinese Pharmacopoeia has been revised over the past,and the quality standards have been continuously improved,but there are still many problems.The main problems are as follows:1.The original medicinal materials are not processed and processed:the quality difference caused by the different producing areas of Danshen and Sanqi,different harvesting periods and different processing methods affects the stability of the compound Danshen tablets.2.Feeding is not standardized:Sanqi is a precious medicinal material,and there are many manufacturers who cut corners for the best interests or replace the Sanqi medicinal materials with Sanqi stems and leaves.3.There is no standard in process technology:the production process and level are different,which causes the difference of compound Danshen tablets from different manufacturers,4.The quality control and evaluation system is imperfect and lacks a whole process quality evaluation system.In view of these problems,it is especially necessary to establish a quality control system for the whole process of compound Danshen tablets from medicinal materials,decoction pieces to preparations to improve the quality of Fufang Danshen tablets and ensure clinical efficacy.This project intends to use compound Danshen tablets as the research object.According to the quality management mode of the whole industry chain of medicinal materials-decoction pieces-finished products,the key steps of quality and safety of the whole process of compound Danshen tablets production are completed,and the processing and preparation of raw materials from the source are completed.The production process involves the production specifications of extraction,concentration and drying,and the formulation of high quality standards.Method:1.Using the high performance liquid phase method,using salvianolic acid b as the internal reference material,establishing the relative correction factor between salvianolic acid b and the other six phenolic acids,and establishing a method for evaluating the multiple evaluation of salvianolic acid.It is applied to the determination of Danshen components in Danshen medicinal materials,intermediates and compound Danshen tablets,and a set of evaluation methods can be applied to the whole process and multi-link detection.2.Optimize the extraction and concentration of Salvia miltiorrhiza in the production and processing of compound Danshen tablets,and clearly extract the parameters such as concentration time and temperature,and optimize the production process of compound Danshen tablets.3.Using the high performance liquid phase method,ginsenoside Rg1 was used as the internal reference substance,and the relative correction factor between Panax notoginseng saponin R1,ginsenoside Re,Rbl and Rd was established,and a saponin component in Fufang Danshen Tablet was established.Multi-evaluation method was applied and applied to the quality evaluation of Sanqi medicinal materials and compound Danshen tablets.4.Using the HPLC method,the fingerprints of Danshen components in the compound Danshen tablets and the fingerprints of the Panax notoginseng components were established,and the fingerprint similarity evaluation system and the combination of cluster analysis and principal component analysis were used.To evaluate the differences between different manufacturers of compound Danshen tablets.Result:1.The relative correction factors of three sets of salvianolic acid components were established in parallel,and the rsd was 1.7%-4.10%.The calculation results of the phenolic acids in Danshen herbs and preparations were compared with the results of external standard method.No significant difference.Drying and drying of 7-8 percent dried Salvia miltiorrhiza collected from the production area was carried out by dry drying and drying.The results showed that the two drying methods had an effect on the content of Salvia miltiorrhiza.In the process of producing,fresh Danshen After the medicinal materials are dried to 7-8,the medicinal materials should be dried in a dry manner to ensure the high quality of the ginseng medicinal materials.By comparing the differences in the content of salvianolic acid in the compound Danshen tablets from different manufacturers,the results showed that the four batches of Guangzhou Baiyunshan Hutchison Whampoa Chinese Medicine Co.,Ltd.had small differences between batches and the process was stable.2.The optimization results of the extraction process of Salvia miltiorrhiza showed that the first step of extraction should be to select 95%ethanol for 6 times for 1.5 hours,the second step for selecting 50%ethanol for 8 times for 2 hours,and the third step for selecting water for 8 times for 2 times.In the hour,the results of the enrichment process showed that the content of phenolic acids changed with the increase of concentration temperature.When the concentration temperature was higher than 80 0C,the effect on b component of salvianolic acid was significant.It is recommended to control the concentration in industrial production,temperature.3.The relative correction factor rsd of the notoginsenosides established in this paper is between 0.53%-4.17%,and the simultaneous determination of five components is realized,and it is applied to the medicines and preparations of Panax notoginseng.There was no significant difference between the results of the multi-assessment of the components of the Sanqi saponins in the compound Danshen tablets and the results of the external standard method.The content of salvianolic acid b and tanshinone iia and notoginsenoside in 73 batches of different Danshen tablets were determined by high performance liquid phase method.The results showed that the quality difference of compound Danshen tablets was different.4.In this paper,fingerprint similarity evaluation was carried out on 29 batches of compound Danshen tablets from 10 different manufacturers.The results showed that the similarity of 29 batches of compound Danshen tablets was above 0.90.Only from the chromatogram and similarity calculation results,the common peaks of Salvia miltiorrhiza in the compound Danshen tablets of different manufacturers are the same,and the similarity is higher.Only the difference in peak area size.Further,the cluster peak analysis and principal component analysis of 12 characteristic peak areas of Danshen components,8 characteristic peak areas of Sanqi type components and 20 characteristic peak areas under the combined action of two components were carried out on 29 batches of compound Danshen tablets.It was found that there were differences in the compound Danshen tablets from different manufacturers.The 29 batches of compound Danshen tablets can be divided into two categories.Among them,No.1(Yunnan Baiyao)is divided into one category,and other manufacturers are divided into one category.It shows that the manufacturer's production process is very different from other manufacturers'processes.Based on the product analysis of Guangzhou Baiyunshan Pharmaceutical,it was found that the batch of C17A029 and other batches of the manufacturer could not be gathered together.The difference of this batch of products needs further analysis.The method can be used to evaluate the overall quality of the compound Danshen tablets.Conclusion:In this study,a method was established to establish a method for the simultaneous determination of medicinal materials-decoction pieces-intermediates · preparations by establishing a test method for the determination of salvianolic acid and panax notoginseng saponins in compound Danshen tablets.Through the combination of fingerprint,similarity evaluation and multivariate statistical analysis methods,the quality evaluation of different batches of compound Danshen tablets from different manufacturers or the same manufacturer can be realized.The research on the extraction and concentration of Danshen in the compound Danshen tablets was carried out to find the mass transfer law of the active ingredients in the production process.The result provides a methodology for the establishment of the quality control system for the whole industry chain of Compound Danshen Tablets,and provides quality control methods for the improvement of the quality of medicinal materials and finished medicine products. |
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