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General Pharmacology And Toxicology Research On Scorpion Venom Peptides For Injection

Posted on:2009-02-12Degree:MasterType:Thesis
Country:ChinaCandidate:T SunFull Text:PDF
GTID:2144360242981613Subject:Pathology and pathophysiology
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Objective:Scorpion (scorpion), which was a primitive carnivorous ARACHNIDA Scorpion , Gan scorpion Branch savings animals. Scorpion is the effect of scorpion venom, scorpion venom is the main traditional medicine Scorpio active substances. In recent years, with the development of molecular biology of the domestic and international biomedical science,we have isolated dozens Chonghe monomer components from scorpion venom poisoning - scorpion venom peptides, which can produce a wide range of pharmacological activity, can be treated more Difficult Diseases of the clinical application of scorpion venom peptide research mainly concentrated in the analgesic, anti-tumor, anti-epilepsy, as well as the role of the cardiovascular area.Analgesia is the main pharmacological effects of the scorpion, by ion-exchange and gel filtration chromatography from the rough isolated from a drug analgesic activity peptide --Scorpion Analgesic Peptide(SAP), SAP has strong analgesic effect. Study found that SAP had a strong effect in inhibiting a variety of acute and chronic pain, and had a good effection to repair the damage of nerve. Scorpion venom active ingredient has a stronger effect in analgesic effect than morphine, no addiction, has its unique advantages and not be depended . If we can isolate more pure analgesic activity peptide components or monomer, it will be a great value and potential new type of analgesic drugs.With the application of modern biochemistry and molecular biology experiments, we can isolate the high purity active ingredients - scorpion venom peptide (peptide of scorpion venom, PSV) from the scorpion venom, different single component has its specific role,and the research on the pharmacological effects of scorpion venom Peptide will provide a theoretical basis for clinical application.With the industrialized environmental pollution and the ageing of the population, the more people who is in risk of cancer and diseases of the pain. The theory study on scorpion venom peptides encourages its clinical application, provides a new clue for the treatment of the diseases,therefore,the scorpion venom tragacanth has a wide perspective. Although, our research for scorpion venom is late,our science exploitation and the research on its mechanisms are advanced. There is a wide market on the scorpion venom peptides isolation, purification, structure analysis and their clinical application, especially in the analgesic, anti-tumor, anti-epilepsy to progress depth research, exploitation and utilization. It will become a new medicine that has high efficiency and low poisonous.So it is imperative to enlarge clinical observation.The objective of this research is on the basis of pharmacy subject in the injection of scorpion venom peptides, through general pharmacological, acute and long-term toxicity studies on the injection of scorpion venom peptides, providing information to consummate its preclinical study.Result:1,The results of the general pharmacological experiments show that: respectively 40μg/kg, 20μg /kg, 10μg/kg muscle administration of the central nervous system in mice, the mice sleep sodium pentobarbital time had no effect ; respectively 40μg/kg, 20μg/kg, 10μg/kg tail vein injection in mice had no effect on the time of the mice stay on the post.The experiment shows that the injection of scorpion venom peptides has no obvious active nor inhibit effect on central nervous system.8.15μg/kg, 4.1μg/kg, 2.0μg/kg muscle administration, there was no significant effects on the cardiovascular and respiratory system of the cat. 2,The results of the acute toxicity experiment show that: injection of scorpion venom peptides intravenous LD50was 0.8808 mg /kg, 95% confidence limit of 0.7385 to 1.0505mg/kg; intramuscular administration LD50 was 1.5331 mg/kg, 95% CI limit of 1.4050 to 1.6612 mg/ kg.3,The results of long-term toxicity studies show that: the medicine effect on the weight and the dose become a gradient relativition.The medicine dose and bone marrow depression become a direct proportion relation. Intramuscular administration of scorpion venom peptide (XTA) 110μg/kg, 47μg/kg in rats has small liver toxicity, and do not have toxic reactions on the other major organs of the body, and the small liver toxicity can gradually resume after drug withdrawal. Low-dose 20μg/kg, the equivalent of 12 times the dose which is used in clinical,(Body weight 60 kg, 100μg/day) is the safe dose.Scorpion venom peptides are the active ingredients isolating from East Asia clamp Hehe drug toxicity, which relative molecular mass is between 6000 and 7000 Dalton. Its different ingredient has their own biologic activity.APBMV can kill many kinds of tumor cells highly selectively , and increase the number of white blood cell and protect bone marrow.It has a good immune modulation features, and combine with radiotherapy and chemotherapy drugs can reduce the side effects of chemotherapy and radiotherapy, improve the immune of normal tissue and increase the capacity to opposite radiation-chemotherapy and radiotherapy. AEP has a obvious effect to opposite epilepsia,and improve the heart rate.SVFAP can forbid the form of throm.. In addition, scorpion venom peptides also have an effect on treating cardiovascular disease by impacting the ion channel.Scorpion venom can educe depressant effect on the nerves function through decreasing the permeability of the membrane to Na K reversiblely.It has highly voltage dependence to excite cells. Scorpion venom can block the new Na K channel on the part, nerves membrane which is damaged, having encourage effect to the morphological, functional and pain hypersensitiveness recovery. Scorpion venom can have an effect on the bloon pressure through changing the permeability of the membrane. Because scorpion venom includes hyaluronidase phosphodiesterase, it can educe a fast function , and its demiperiod is short, toxic reaction is quickly. It can also repress the tumor neovascularity through inhibit the express of Cox-2 to repress the metabasis of the cancer. ConclusionTo sum up, through the general pharmacological and acute toxicity research of the injection of scorpion venom peptides,the injection of scorpion venom peptides is safe in the experiment administration dose and can be played its corresponding pole by intramuscular. Long term toxicity test shows that intramuscular in the rice has small liver toxicity, and do not have obvious toxic reactions on the other major organs of the body, and the small liver toxicity can gradually resume after drug withdrawal. Low-dose 20μg/kg, the equivalent of 12 times the dose which is used in clinical,(Body weight 60 kg, 100μg/day) is the safe dose.The results of this research on scorpion venom peptides provides a new idea and rationale for endering the clinical of scorpion venom.
Keywords/Search Tags:Scorpion venom peptides, pharmacology, toxicology
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