| Shuxuening injection is the preparation of Ginkgo biloba extract, The research and development on the use of Ginkgo biloba has also been popular in the last half century the world.Through long-term study, the efficacy of Ginkgo biloba extract effect, pharmacological mechanisms and clinical applications have been widely recognized, fully understand and in-depth study. Beijing drug testing where the 2009 evaluation of the national traditional Chinese medicine injection testing, we found that different manufacturers, injection of Shuxuening has different production processes, some production factors may affect the clinical safety and effective; to further enrich the basis of pharmacodynamic research data, to ensure their safe and effective, so re-evaluation of its pharmacodynamics, re-evaluation of pharmacodynamics including myocardial ischemia, cerebral ischemia, thrombosis and microcirculation of four main aspects experiments.Currently Chinese medicine is complex, but a single control the small number of index components is difficult to control the safety and efficacy of drugs, this forces us to improve the existing method of quality control. Bioassay has matured in recent years, and bioassay has occupied a dominant position in some western of quality control, so the use of biological assays for quality control of traditional Chinese medicine is an inevitable trend. A edition of 2010 Chinese Pharmacopoeia, increased the guidelines of the biological activity of traditional Chinese medicine, in order to further improve the quality control method of traditional Chinese medicine, stating that especially in traditional Chinese medicine quality standards updated the bioassay is a direction.If you can take the lead in traditional Chinese medicine quality standards, development of biological activity will also largely improve the accuracy of quality control and speed up the modernization drive.So the present research study the Shuxuening injection of several basic pharmacological effects depth, through scientific and experimental design of dose indicators, in order to ensure the injection Shuxuening safety and effective in clinical using and provide basic research data. Pharmacodynamic study found Shuxuening injection have good inhibition of platelet aggregation in vivo and in vitro, and have a good and clear dose-effect relationship, to the biological effects-based, bio-statistics as a tool, the use of a specific experimental design to quantify the biological activity of drugs, established the methodology of Shuxuening injection for platelet aggregation in vitro biological activity test, to add its quality control methods. The experiments included re-evaluation of Pharmacodynamic and assay of biological activity of platelet aggregation in vitro, discussed separately below.First part Re-evaluation of Shuxuening injection of pharmacodynamicFirst, Shuxuening injection on myocardial ischemia:using sublingual injection of pituitrin to cause acute myocardial ischemia, investigated the changes of ST segment in ECG and heart rate before and after administration of modeling, changes in myocardial infarct size, changes of LDH, CK, MDA, SOD and other biochemical in serum. The results showed that Shuxuening injection can inhibit the elevated of ST segment in the first phase of myocardial ischemia, the reduction of the ST segment in the second phase, against heart rate slowing by the pituitary induced in rats. It could also reduce the positive rate of myocardial ischemia and the incidence of arrhythmia, reduced infarct size and infarct rates of rats with myocardial ischemia. Reduced the content of LDH, CK, MDA and increased activity of SOD in serum. So the mechanism of Shuxuening injection against myocardial ischemia may be to reduce the release of harmful enzymes in myocardial cells, improved the free radical metabolism and antioxidant effects.Second, Shuxuening injection on cerebral ischemia:by the experimental model of cerebral ischemia through ligation the bilateral carotid artery in mice, ligation the bilateral common carotid artery and vagus nerve of mice after administration, studied the survival time of mice, infarct size, brain index of brain and measured the MDA, SOD, LDH and other biochemical parameters in brain. The results showed that Shuxuening injection could extend the survival time in mice with acute incomplete cerebral ischemia, and cerebral edema, decreased infarct size, reduced infarction rates. At the same time can improve the content of SOD in brain tissue and reduce the MDA content, reduce free radical damage and reduce the release of LDH with in the brain tissue, compete the damage of oxidative tissue in rain, enhanced the protective effect of brain tissue, So the mechanism of Shuxuening injection in cerebral infarction may be related to antioxidant effects.Third, the effect of antithrombotic in Shuxuening injection:by subcutaneous injection of epinephrine hydrochloride with an ice bath to make acute blood stasis model rats, after 1h of the modeling administered once, and 15min before surgery then administered other once, though the electrical stimulation caused the carotid artery thrombosis, recorded the length of thrombus and formation time of thrombus, determined the plasma prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet aggregation, measured the viscosity of whole blood and plasma. Shuxuening injection can extend the time of suppository in blood stasis model rats, shortened the length of the bolt, significantly prolonged the longer time to 50% into the bolt, the initial formation of thrombus good inhibition, have a good inhibition of the initial formation of thrombus. It could also lower the platelet aggregation rate of blood stasis model of plasma in rats, prolonged the coagulation time of prothrombin (PT) and activated partial thromboplastin (APTT), reduce the viscosity of whole blood and plasma, So the antithrombotic mechanism of Shuxuening injection may related to reduce platelet aggregation,prolong clotting time and lower blood viscosity.Four, the function of Shuxuening injection on improvement of microcirculation:Study the effect of normal and blood stasis model rat's ear arteriole, venule and the number of capillaries open cross-influence after medication, through the results we can seen that Shuxuening injection can expand the normal mouse ear arteriole and venule diameter, increased the number of capillaries open to cross-network; improved blood flow of stasis model rats, made the most of the flow from the particle flow for the mitochondrial flow, then its indicated that Shuxuening injection have the effect of improved the microcirculation, and had a good dose-dependent.Second part Construction the bioassay method of Shuxuening injection oplatelet aggregation in vitroInduced by ADP and PAF are two agents, conducted the inhibition of platelet aggregation experiments of Shuxuening injection and Ginaton injection in vitro, the results show that Shuxuening injection have a better platelet aggregation inhibition of blood induced by ADP and PAF. Through linear relationship visits, found that by a logarithmic transformation of the maximum platelet aggregation rate have a good linear relationship with the dose. Ginaton injection was standard, using the bioassay method of the amount of reaction in three methods for the parallel three to determination the titer, at the same time testing the reliability and repeatability of inspection. Reliability test show that the method of measured the titer were obtained by the method were reliable, repeatability study showed that the platelet aggregation bioassay method established by two inducer in vitro had a reproducible, biological potency of Shuxuening injection were reliable which measured out by the method, it was feasible, further research can speed up the determination of biological activity for the process of quality control. |
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