血塞通络泰药理[1].ppt

1、Introduction of Panax Notoginseng Saponins （PNS） And its Preparations Panax Notoginseng Injection Soft capsule; Injection; Freeze-drying powder injection, etc. These kinds of preparations containing Panax Notoginsenosides have been applied in clinics for treating apoplexy and its sequela (hemiplegia

2、), deflection of mouth and eyes，language obstacle, chest pain (myocardial infarction, coronary heart disease, and angina pectoris)，facial paralysis and ophthalmocace.,The Key Panax Notoginseng Saponins products of KPC include Panax Notoginseng Saponins Injection (Xuesaitong Injection) and freeze-dry

3、ing powder of Panax Notoginseng Saponins For Injection (Luotai).,Panax Notoginseng Saponins Injection,Panax Notoginseng Saponins Injection (Xuesaitong Injection) Developed and manufactured first by KPC in the early 80s Acquired the certificate of new drug and authorization document of production in

4、1985 Listed as the protected product of State Traditional Chinese Medicines in 1996 Recorded in the State Pharmacopoeia of China in1998 Specifications: 100 mg/2 mL; 200 mg/2 mL; 250 mg/5 mL; 250 mg/10 mL,Usage and Dosage Intravenous drip: Once a day, 200-400 mg/Once, slowly dripped after diluted in

5、250-500 mL (5% or 10%) of Glucose Injection Intravenous injection: Once a day, 200 mg every time, slowly injected after diluted in 40-60 mL (25% or 50%) of Glucose Injection The period of treatment is 15 d,Panax Notoginseng Saponins for Injection,Based on Xuesaitong Injection, Luotai was refined by

6、KPC through high and new technology. It is a freeze-drying powder injection.,Freeze-drying powder for injection Panax Notoginseng Saponins for Injection ( Luotai ),Three patents product patent, special purpose solvent patent, and package patent 6 items of state and provincial prizes Listed as state

7、standard medicine, acquired production document issued by CFDA Specifications: 200 mg/Ampoule, 400 mg/Ampoule,Freeze-drying powder injection Panax Notoginseng Saponins for Injection ( Luotai ),Usage and Dosage Dissolved in the special purpose solvent before use. Intravenous drip: Once a day, 200-400

8、 mg/Once, slowly dripped after diluted in 250-500 mL (5% or 10%) of Glucose Injection Intravenous injection: Once a day, 200 mg every time, slowly injected after diluted in 40-60 mL (25% or 50%) of Glucose Injection The period of treatment is 15 d,PNS decreased apoplexy index caused by brain ischemi

9、a-reperfusion injury, improved ischemic symptoms, lowered Ca2+ content in ischemic brain tissue, and showed significant protective effect on the delayed injury of CA1 section in hippocampus,Pharmacology of PNS IProtection against ischemic brain injury,20-30 min after administered intravenously, PNS

10、(100 mg/kg) could gradually increase brain blood flow in rabbits. PNS could dilate the contracted cerebral vessels. Anti-anoxia effect： PNS elevated the tolerance of mice to anoxia under normal air-pressure, but not under low air-pressure.,Pharmacology of PNS IProtection against ischemic brain injur

11、y,PNS, in vitro or in vivo, significantly inhibited platelet aggregation induced by adenosine diphosphate, arachidonic acid, and platelet-activating factor, in a concentration-dependent manner. Decreasing platelet serotonin, lowering cytosolic calcium and elevating platelet cAMP level are closely in

12、volved in the anti-platelet aggregation of PNS.,Pharmacology of PNS II. Anti-platelet aggregation effects,Platelet hyperfunction plays an important role in the occurrence and development of cerebral-ischemic diseases. PNS are advantageous to cure and prevent brain ischemia, cerebral infarction and t

13、he related sequela.,Pharmacology of PNS II. Anti-platelet aggregation effects,PNS decreased mouse mortality challenged by injection of arachidonic acid, and prolonged the occlusion time in electrically-stimulated rat carotid arteries.,Pharmacology of PNS III. Anti-thrombotic effects,Pharmacology of

14、PNS IV. Thrombolytic effects,PNS increased reperfusion rate and decreased reclusion rate in rats with arterial thrombus.,Elevated the activity of tissue-type plasminogen activator (tPA) while decreased that of plasminogen activator inhibitor type-1 (PAI-1).,Mechanism of PNS,tPA is recognized as a ma

15、jor starting factor of fibrinolytic system. PAI-1, on the other hand, binds rapidly to tPA, forming a stable complex. Release of PAI-1 from activated platelets plays an important role in the pathogenesis of arterial thrombosis and inhibiting lysis of thrombi. Evidence is growing that elevated PAI-1

16、activity is a risk factor in thromboembolic disease as a result of reduced fibrinolytic activity.,Mechanism of PNS,In fact, elevated PAI-1 activity has been reported in patients with cerebral-ischemic diseases, coronary artery disease, and myocardial infarction. Inhibition of PAI-1 and subsequent in

17、crease of tPA may therefore result in enhanced endogenous fibrinolysis. PNS showed inhibition of PAI-1 activity and elevation of tPA activity; it is beneficial to promote the reperfusion and suppress the reocclusion especially in cerebral-cardiac-ischemic diseases.,In the model of rabbit normal-air

18、pressure anoxia, intravenous PNS markedly modified the dilation of micro-veins in soft meninges, prolonged the accelerating time and delayed the stagnate (ceasing) time of capillary vessels. It is suggested that PNS showed the improvement on microcirculation of soft meninges. In addition, PNS had th

19、e similar effects on the other tissues. Obviously, PNS is advantageous to prevent and cure apoplexy and its sequela (hemiplegia).,V. Effects of PNS on microcirculation,Inhibited CaCl2-induced constriction of pig coronary artery Suppressed calcium influx into myocardiocytes Elevated the plasmic calci

20、um concentration of endothelial cells Inhibited calcium uptake into synaptic body Indicating PNS is a calcium channel blocker.,VI. Effects of PNS on calcium channel,In the model of gerbil ischemia-reperfusion injury, PNS increased the content of LDH and SOD while decreased the formation of MDA and T

21、XB2. Inhibited xanthine- or xanthinoxidase-stimulated generation of free radicals from myocardiocytes. Mechanism: directly scavenge; Increased SOD activity; Improve the tolerance to anoxia and protect mitochondrion function,VII. Effect of scavenging free radicals,As serious cerebral ischemia occurs,

22、 a lot of free radicals generated, and resulted in a further injury of nerve cells. It is indicated that the effect of PNS on scavenging free radicals may contribute to its clinical use for ischemic cerebral vascular diseases.,Pharmacokinetics of PNS Distributionliver, kidney, adrenal, lung, heart,

23、spleen, brain, eyes, etc. Concentration-time curve showed a two-compartment model.T1/2 of distribution: 11 min.,Pharmacokinetics of PNS Elimination T1/2 of elimination: 4.4 h Excretion Excreted mainly with urine, dung, and bile,Toxicity Acute toxicity The median lethal dose (LD50) : 292.3 mg/kg (PNS

24、 injected in the mouse tail vein); 683.1 mg/kg (intramuscular injection),Toxicity Chronic toxicity After Beagle dogs were intravenously injected for 90 d, the animals just in high dose group had a few toxic reaction, showing body weight lessened, poor appetite and decreased food-taking.,Characterist

25、ics and advantages of Panax Notoginseng Saponins for Injection In recent years, with the progress of equipment and facilities of freeze-drying powder injection, it is possible to apply this new preparation to natural drugs. Freeze-drying powder injection shows special techniques.,Characteristics and

26、 advantages of Panax Notoginseng Saponins for Injection First, the solution of effective components is frozen as ice crystal. Second, in low temperature and decompression, the ice crystal is sublimed and then dried. The effective component is therefore reserved and shaped.,Characteristics and advantages of Panax Notoginseng Saponins for Injection Because of this special technical process, the effective components are seldom decomposed, by effectively avoiding destroy of high temperature, high humidity, solvent, or the chemical reactions with supplement materials. In addition, owing to