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目的:根据我国相关法规,开展治疗性乙肝疫苗的长期毒性试验。方法:将治疗性乙肝疫苗以高、中、低三个剂量经皮下注射食蟹猴,另以等体积生理盐水作为空白对照,每天给药1次,连续21 d,停药后继续观察4周。以血常规、尿常规、血生化、血清抗体和补体、病理学等为观察指标。结果:各组动物外观、行为活动未见异常,未见死亡;试验组动物对受试疫苗均产生免疫应答,血清中可检测到相应抗体;高剂量治疗性乙肝疫苗对食蟹猴肝、肾功能指标有一定影响,停药后可恢复;未见明显的迟发性毒性反应。结论:治疗性乙型肝炎疫苗安全性良好,对食蟹猴的最大无毒作用剂量为21μg·kg~(-1),约为人临床拟用剂量的21倍,以体表面积计,约为单次人临床拟用量的8倍。
Objective: To carry out the long-term toxicity test of therapeutic hepatitis B vaccine according to relevant laws and regulations of our country. Methods: The therapeutic hepatitis B vaccine was injected subcutaneously into cynomolgus monkeys at high, medium and low doses, and the same volume of normal saline was used as blank control. The medicine was administered once a day for 21 consecutive days and continued for 4 weeks . To blood, urine, blood biochemical, serum antibodies and complement, pathology and other indicators for the observation. Results: The appearance and behavior of animals in each group showed no abnormalities and no death was observed. All the animals in the experimental group had an immune response to the vaccine tested and the corresponding antibodies were detected in the serum. High-dose therapeutic hepatitis B vaccine showed no effect on cynomolgus monkey liver and kidney Functional indicators have a certain effect, after stopping can be restored; no significant delayed toxic reactions. Conclusion: The therapeutic hepatitis B vaccine is safe and has the maximum non-toxic dose of 21μg · kg -1 to cynomolgus monkeys, which is about 21 times of the dose of human clinical trial. Based on body surface area, Secondary clinical dosage to be 8 times.