ABSTRACT
The current drug non-clinical safety evalua-tion has been highly systematized and standardized, but the standard toxicology model is still some inade-quacies, need to consider other animal models of safety evaluation. This paper will expound the need of animal disease models using in safety evaluation from the as-pect of scientific theories, data requirements and the need of clinical. Then recognizing on the perspective of drug regulatory agencies to explore the feasibility of u-sing animal disease models for safety evaluation and the deficiencies, in order to predict as accurately as possi-ble of the adverse drug reactions in clinical, applied to reduce the risk of clinical patients ( patients benefit ) , and reduce the risk of drug development failures ( pharmaceutical companies benefit ) . All in all we should attach great importance to the applications of animal disease models in non-clinical safety evalua-tion.
ABSTRACT
Objective To study the protecitve effect of methy Protodioscin(MPD)on myocardial infarction in dogs. Methods Dog models of myocardial infarction were induced by ligation of coronary artery. The degree of myocardial ischemia was calculated by measuring the epicardial electrogram, and the myocardial infarction area was detected with N-BT histochemistry staining method. The changes of ET, 6-Keto-PGF1a, TXB2 in blood plasma were observed with radioimmunoassay. Meanwhile, the coronary blood flow was measured. Results MPD can obviously relieve the pathological changes of the acute myocardial infarction, decrease the infarction size, reduce the myocardium ischemic degree, dilate the coronary artery , and increase the myocardial blood supply. Meanwhile, MPD can improve the vascular endothelial cell function. Conclusion MPD had obvious effect for relieving acute myocardial infarction in dogs.
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Objective To investigate the pharmacological effects of MPD on heart hemodynamics and myocardial oxygen consumption in dogs, and to study its mechanism. Methods The changes of parameters such as blood pressure (BP), coronary blood flow, myocardial oxygen consumption and heart rates were observed in normal anesthetic dogs. Results Compared to those in the normal group, MPD can obviously lower the BP and peripheral vascular resistance, dilate the coronary and peripheral artery, increase the coronary blood flow and improve the left ventricle function and myocardium oxygen consumption rate. Conclusion MPD can improve the heart hemodynamics and regulate myocardium oxygen consumption.
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Objective To investigate the pharmacological action of Shuanglong Prescription on cardiac function in dogs and to study its mechanism. Methods The changes of the parameters such as coronary blood flow, myocardial oxygen consumption and heart rates were observed in normal anesthetic dogs. Results Compared to those in the normal group, the coronary blood flow increased and the heart rates decreased in Shuanglong Prescription group. Conclusion Shuanglong Prescription can regulate and improve the cardiac function of dogs.
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Objective To study the therapeutic effects of methyl protodioscin (MPD ) on myocardial infarction in rats. Methods Rat models of myocardial infarction were induced by ligation of coranary artery. Then myocardium infarction area and the vasoactive substance were measured to evaluate the therapeutic effect of MPD on acute myocardial infarction in rats. Results Compared with the control group,MPD lessened the myocardial infarction size dramatically,inhibited the increase of CK and LDH ,lowered the increased MDA content level and improved the activity of SOD and NO. Conclusion MPD reduces the level of myocardium enzyme and the myocardial infarction size,and increases the capability of clearing oxygen free radical and function of the vascular endothelial cell. MPD by intravenous injection has a better effect than that by oral use.
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Objective To investigate the effects of methyl protodioscin (MPD ) on in-vitro and in-vivo thrombosis and blood viscosity in rats. Methods The vitro thrombus was induced by Chandler method,and the length,wet and dry weight of the thrombus were measured. Thrombosis instrument was to observe the in-vivo occlusion time (OT). At the same time,determined the high-,middle-,low-shear blood viscosity as well as the plasma viscosity in rats was determined .Results Compared to normal group,middle-dose MPD group can delay the OT,and the high-dose group can decrease the length,wet and dry weight of in-vitro thrombus. The blood viscosity is reduced in all groups. Conclusion MPD can inhibit the in-vitro thrombosis,decrease the dry and wet weight of thrombus and delay the OT. Moreover,MPD has the effects of lowering the whole blood viscosity and plasma viscosity.
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Objective To study the therapeutic effects of Shuanglong Prescription (SP) for experimental myocardial infarction in rats. Methods Rat models of myocardial infarction were induced by ligation of coronary artery. Fourteen days after treatment, myocardial infarction area, biochemical parameters and myocardial capillary density were detected to observe the effect of SP.Results After 14- day treatment, SP could reduce the area of myocardial infarction, increase the ratio of 6- keto- PGF1? and TXB2 and the capillary density.Conclusion SP has certain therapeutic effect for myocardial infarction in rats.