大鼠长期吸入尼古丁雾化剂（“如烟”烟液）的安全性评价

发布时间：2018-01-29 14:49

本文关键词： 安全性评价尼古丁柯廷宁　出处：《吉林大学》2006年硕士论文　论文类型：学位论文

【摘要】：药物安全性评价是新药开发过程中不可缺少的部分。目前药物安全性评价的基本手段是动物毒性实验,主要研究动物给药后的表现、血液学、临床生物化学和组织病理学等指标,作为器官损伤的指示剂,进行药物毒性的评价,并将此毒理学研究结果外推至人—中毒原型,以便最终能够保证人类健康。但是动物与人之间的种属差异,给临床试验和新药上市后毒性反应得监测造成很大压力。近年来,毒代动力学以及毒理基因组学的飞速发展,为解决传统动物毒性评价实验中所面临的和多问题,逐步完善药物安全评价体系,提供了新手段。 “如烟”是采用世界卫生组织力推的“尼古丁”替代法,顺应烟民多年养成的吸烟习惯,模拟吸烟的全过程,与吸烟动作完全相同。“如烟”产生的烟雾不含有害物质,自己吸无毒,也消除了“二手烟”的危害,同时避免了因突然戒烟而引起的不适症状。由于吸烟人数众多,为了给公众一个交待,以药物的标准对其及进行安全性评价是很有必要的。因此,我们对“如烟”进行了长期毒性研究。我们还探讨大鼠暴露于香烟烟气或尼古丁雾化环境中,体内尼古丁实际摄入量的测定方法。考察了氰化钾—巴比妥酸法作为测定尿中尼古丁代谢产物柯廷宁的可靠性。
[Abstract]:Drug safety evaluation is an indispensable part in the process of new drug development. At present, the basic method of drug safety evaluation is animal toxicity experiment, mainly to study the performance of animals after administration, hematology. Clinical biochemistry and histopathology, as indicators of organ injury, were used to evaluate the toxicity of drugs, and the toxicological results were extrapolated to the prototype of human-poisoning. But species differences between animals and humans have put a lot of pressure on clinical trials and the monitoring of post-marketing toxicity of new drugs. The rapid development of toxicokinetics and toxicology genomics provides a new method to solve the problems in traditional animal toxicity assessment experiments and to gradually improve the drug safety evaluation system. "such as smoke" is to adopt the "nicotine" substitution method promoted by the World Health Organization, comply with the smoking habit developed by smokers for many years, and simulate the whole process of smoking. And smoking action is exactly the same. "such as smoke" produced smoke does not contain harmful substances, their own non-toxic, but also eliminate the "second-hand smoke" harm. Because of the large number of smokers, it is necessary to evaluate the safety of drugs according to the standard of drugs in order to give an account to the public. We have conducted a long-term toxicity study on "smoke". We also investigated the exposure of rats to cigarette smoke or nicotine nebulization. The reliability of potassium cyanide-barbituric acid method for the determination of nicotine metabolite cotinine in urine was investigated.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R363

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