| Traditional Chinese medicine is a complicated system with many components, physical and chemical properties of the chemical composition are different,and the component is not clear, these have become the main factors restricting the development of the traditional Chinese medicine. The research of traditional Chinese medicine preparation must consider the overall effect of Chinese herbs nature of the multi-component and multi link multiple targets. With the development of modern preparation technology and polymer material science, dosage forms become diverse, but also the research of traditional Chinese medicine preparation is enriched. We took salvianolic acid components as the research model, and discusse the new research ideas of Chinese traditional medicine preparation based on the traditional Chinese medicine components. The main research contents are as follows:Chapter1To explain how to establish the Chinese medicine components release unit and expound the research of total salvianolic acid components. Under the guidance of Chinese medicine theory, we explore the new study mode of traditional Chinese medicine preparation that the traditional Chinese medicine components is divided into functional units from the traditional Chinese medicine research foundation, characterization of the traditional Chinese medicine components, studying on structure optimization of the traditional Chinese medicine components、establishing the Chinese medicine components release unit、evaluation of the Chinese medicine components release unit. On the other hand, we deeply summarize the total salvianolic acid components about the research of salvianolic acid chemical ingredients, pharmacological effect、bioavailability and preparation.Chapter2To screen the representative components of total salvianolic acids by human umbilical vein endothelial cell injury model induced by hydrogen peroxide oxidation.The results show that oxidative damage induced by H2O2can be inhibited by salvianolic acid components and different compositions, and salvianolic acid components has certain protective effect on endothelial cells. Compared with the salvianolic acids, there were no significant differences with salvianolic acid B+rosmarinic acid+danshensu group and salvianolic acid B+rosmarinic acid+danshensu+salvianolic acid A group on influencing cell survival rate and improving SOD, MDA, LDH and NO release. Secondly, to screen the representative components of total salvianolic acids through in vitro four coagulation method, and the results show that salvianolic acid components and different compositions has little effect on the PT, but they significantly prolonged APTT and TT, and decrease the content of FIB. Compared with the salvianolic acid components, salvianolic acid B+rosmarinic acid+danshensu group and salvianolic acid B+rosmarinic acid+danshensu+salvianolic acid A group have no significant difference in the experimental results. Finally, to verify the representative components of total salvianolic acids through the myocardial ischemia rat models induced by ISO.There are no significant difference in the inhibition of ST segment elevation between total salvianolic acids、salvianolic acid B+rosmarinic acid+danshensu group and salvianolic acid B+rosmarinic acid+danshensu+salvianolic acid A group. At the same time, the three groups of drugs have no significant difference in reducing the serum CK, LDH, AST content, reducing myocardial MDA content and increasing SOD activity and NO content. Compared with the salvianolic acid components, salvianolic acid B+rosmarinic acid+danshensu group and salvianolic acid B+rosmarinic acid+danshensu+salvianolic acid A group have no significant difference in these pharmacological experiments results. Taking into account the salvianolic acid A detection more difficult, salvianolic acid B, danshensu and rosmarinic acid are laid down as the representative of salvianolic acid components.Chapter3To measure equilibrium solubility, oil/water partition coefficient and permeability of total salvianolic acid components.These biopharmaceutical properties are analysised by the similarity analysis method based on cosine, euclidean distance and Q-test. And the results showed that their biopharmaceutical properties are similar. Effects of contribution rate of each component are calculated by multi index comprehensive evaluation method based on CRITIC weights. We characterizate the total salvianolic acid components based on a mathematical formula of combinating the approach of self-defined weighting coefficient with effects of contribution rate. The results showed that the equilibrium solubility of the total salvianolic acid components is between13.68～19.67mg·mL-1. And the oil/water partition coefficient values rangs from0.02to1.06, and the apparent permeability coefficient is0.77. The result showed that salvianolic acid component is easy to dissolve and difficult to penetrate which belongs to the type Ⅲ drug.Chapter4To design the drug release unit which to improve its bioavailability according to the defect of salvianolic acid components biopharmaceutical properties. To prepare total salvianolic acids phospholipid complex by the conditions that THF were used as reaction solvent, concentration of total salvianolic acids in solvent was5mg·mL-1, mass ratio of total salvianolic acids and phospholipid was1:1.5, react was performed for3.0h at40℃. Total salvianolic acids-phytosome-HA coprecipitate are prepared by means of solvent evaporation,and when the ratio of drug to HA is1:2, it has a better dissolution, the accumulative drug-release percent in vitro at60min is over90%. At the same time, its micromeritic properties have improved. The total salvianolic acids-phytosome-HA coprecipitate pellets are prepared by extrusion spheronization.The preparation conditions are optimized and the roundness and yield of pellets are used to evaluate the quality. The optimal preparation conditions are as follows:the main agent30g, MCC18.5g, CMS-Nal.5g,40%ethanol as wetting agent. The optimum preparation process for extrusion frequency and pheronization frequency is30Hz and40Hz, and the spheronization time is5min.The micromeritic properties of the pellets is good and the accumulative drug-release percent in vitro at120min is94.73%.The three representative components of dissolution is similar.Chapter5To evaluate the bioavailability of total salvianolic acids-phytosome-HA coprecipitate release unit.To compare the effects of the total salvianolic acid components and drug release unit on platelet aggregation in rats induced by ADP, the results show that the inhibitory effect of release unit is higher significantly than that of salvianolic acid components.Chapter6Summarizing and look forward to all the work. |
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