| Traditional Chinese medicine preparation is the link between traditional Chinese medicine and its clinical prevention and treatment.The research of preparation raw materials is the basis of traditional Chinese medicine preparation and affects the clinical efficacy of traditional Chinese medicine.The component structure study is the key to obtain the raw materials of future component Chinese medicine preparation,which contains the scientific connotation of the screening and identification of the representative components of traditional Chinese medicine components,the optimization of the component structure,and the characterization of the overall properties of the components.This thesis was based on the sub-project "Research on the design technology of active ingredient groups in traditional Chinese medicine related to blood stasis type chest pain"(Project number:2008BAI51B03)in the National Eleventh Five-Year Support Plan named "Research on the design technology of traditional Chinese medicine formula based on the active ingredient groups of traditional Chinese medicine".The traditional Chinese medicine Panax notoginseng in "Shen shao shu xiong fang" was selected as the research object,and some modern scientific technologies were used to screen and identify representative components of the active components of Panax notoginseng for the prevention and treatment of myocardial ischemia,to analyze the structure feature of the components,and to integrally characterize the biopharmaceutical properties of the components.The main contents in the research are as follows:1.Identification of representative components of saponin components for the prevention and treatment of myocardial ischemia in Panax notoginsengAccording to the TCMSP database;molecular docking of 119 components of Panax notoginseng with key receptor proteins of myocardial ischemia and activity comparison screening with marketed drugs revealed that the libdockscore score of saponins were greater than the average value of marketed drugs and highly similar to their residues,confirming that Panax notoginseng saponin components were active components for preventing and treating myocardial ischemia in Panax notoginseng.By Mass spectrometry identification of the blood infusion components of Panax notoginseng saponin components,it was found that the blood infusion components were notoginsenoside Ri,ginsenoside Rgi,ginsenoside Rbi,ginsenoside Rd.It was known that the representative components of Panax notoginseng saponin components were notoginsenoside Ri,ginsenoside Rgi,ginsenoside Rbi,and ginsenoside Rd through the screening and identification.2.Structural analysis and optimization of Panax notoginseng saponin components for prevention and treatment of myocardial ischemiaHPLC was used to analyze the primary structure of Panax notoginseng saponin components,the content of notoginsenoside Ri was 7.82%,the content of ginsenoside Rgi was 29.93%,the content of ginsenoside Rbi was 33.86%,and the content of ginsenoside Rd was 8.64%.The quantity ratio relationship of the four components was 1.00/3.83/4.33/1.10.The DPPH,·OH,O2·-free radical in vitro reaction system was established,and it was found that the solution of Panax notoginseng saponin components with different concentrations had certain scavenging capacity for different free radicals.Considering the comprehensive factors,the original components concentration of 0.62 mg/mL was selected as the basis for the uniform design,and six optimized structure groups of Panax notoginseng saponin components were designed by the uniform design method.The structure of Panax notoginseng saponin components was optimized by free radical scavenging experiments in vitro.The results showed that the best optimized structure group of the Panax notoginseng saponin components was notoginsenoside Ri/ginsenoside Rgi/ginsenoside Rbi/ginsenoside Rd=1/7.66/12.96/6.60.3.Efficacy verification of Panax notoginseng saponin components for the prevention and treatment of myocardial ischemia in vivoIsoproterenol hydrochloride(ISO)was injected subcutaneously(10 to 50 mg/kg/d for 2 consecutive days)to prepare a model of myocardial ischemia in rats.From various perspectives of electrocardiograph,cardiac index,myocardial enzymes,and lethality,the modeling dose was set as 30 mg/kg/d for 2 consecutive days.The pharmacodynamic doses of Panax notoginseng saponin components in preventing and treating myocardial ischemia were studied.From the perspective of the effects of myocardial enzymes(AST,LDH)and oxidative stress(SOD)on myocardial injury,it was found that the dose of 200 mg/kg/d for 7 consecutive days was excellent in reducing myocardial damage and improving the body's antioxidant capacity.Therefore,this dose was used as a efficacy verification dose for comparison with the optimized Panax notoginseng saponin components group in vivo.Validation studies had shown that the optimized Panax notoginseng saponin components group can obviously improve the pathological morphology in rats with myocardial ischemia by HE and it could obviously reduce the activity of AST and LDH in the serum of myocardial ischemic rats,increase the activity of SOD and reduce the content of MDA,indicating that it had a significant protective effect on myocardial ischemic injury in rats.4.Characterization of the overall biopharmaceutical properties of Panax notoginseng saponin componentsThe equilibrium solubility and oil-water partition coefficients of representative components of Panax notoginseng saponin components were measured under different pH phosphate buffer environments,and similarity analysis was performed with vector angle cosine function method.The similarity coefficients between the two components were greater than 0.90,indicating that the similarity of the equilibrium solubility and the oil-water partition coefficient of the representative components of the Panax notoginseng saponin components.The mass weight coefficient was introduced to characterize the overall biopharmaceutical properties of the Panax notoginseng saponin components.And.it was found that the overall equilibrium solubility of the Panax notoginseng saponin components was 51.72-69.63 mg/mL.However,the physicochemical properties(solubility)can not roundly represent the dissolving properties of biopharmaceutical properties.After the conversion of required amount solvent of the per unit dose,it was found that the dissolving performance of Panax notoginseng saponin components was high.The overall oil-water partition coefficient of the Panax notoginseng saponin components was 0.49-1.76,which belonged to the category of low permeability.According to the Chinese Medicine Component Biopharmaceutics Classification System(BCSCC),the Panax notoginseng saponin components belonged to the high-solubility,low-permeability drugs as a whole. |
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