| "RuYan" is the substituent of the nicotine recommended by the WHO. Itaccustoms the smoking habit kept by the smokers, simulates the wholesmoking process and is identical with the smoking action. The smog producedby the "RuYan" doesn't contain any noxious substance. It does no harm to thesmoker himself, eliminates the harm of "second-hand smoke" and at the sametime avoids the indisposition symptom originated from the outbreak of smokeabatement. For the smoking population is so large, in order to give the publican explanation, it is necessary to carry out the safety evaluation of the"RuYan" according to the drug standard. For the above reasons, we shouldcarry out the long term toxicity research on "RuYan". The drug safety evaluation is an essential part of the process of drugdevelopment. At present, the fundamental means of drug safety evaluation isthe animal toxicity experiments. It is focused on the behavioral, hematological,clinical biochemical and histopathological index of the post-drug animal as theindicator of the organ impairment to evaluate the drug toxicity, and thetoxicological results could be extrapolated to the human –toxication prototypefor the assurance of the human health. While, the reason of the speciesdifferences between animal and human have posed the great pressure on theclinical experiments and the monitoring of the post-market drug toxic reaction.Recently, the rocket development of the toxi-dynamics and the toxicologygenomics have provided new means for the solution of problems faced duringthe traditional animal toxicology evaluation process and the step-by –stepconsummation of the drug safety evaluation system.During the "RuYan" long term toxicology experiments, the rats continuouslybreathe in the drug for six months, once a day. Set the groups of the control,low, middle and high dosage. Each group contains thirty rats, half male andhalf female. One third of the rats were killed after three-month medication,another one third were killed after six-month medication, the remained onethird were killed on one-month after drug withdrawal.On the 3-month-medication, 6-month-medication and one-month afterdrug withdrawal, we determined some indicators as the blood chemistry,routine urine, blood coagulation time, blood-serum antibody(IgG, IgM, IgA),the blood T leukomonocyte percentage(CD4,CD8), the ratio of CD4/CD8, theorgan weights and histopathology.Blood-serum biochemical indicator includes total cholesterol, alanineaminotransferase, aspartate amino transferase, alkaline phosphatase, ureanitrogen, creatinine, blood glucose, volume dose of bilirubin, total protein,albumin, triglyceride, creatine kinase, kalium ion, sodium ion, and chloridion.We also investigate the method of measuring the content of nicotine in the blood ofrat exposed in burning cigarette smoke or nicotine-fog. The method is the potassiumcyanide-barbituric acid method for determining cotinine, the metabolite of nicotine, in theurine of rat was evaluated. The nicotine solutions of various concentrations wereinfused to rats through tail vein with stable rate for one hour to make the standardcurve of nicotine in the blood of rat. Then, the total urine of 60h was collected and thecontent of cotinine in the urine was measured as the output of nicotine from rat. Thestandard curve was established between the standard control of nicotine and the output ofnicotine. The rats were exposed to the box filled with burning cigarette smoke ornicotine-fog for 1h, the total urine of 60h was collected and the content of cotinine inthe urine was measured, and the absorbed content of nicotine in the blood of rats werecalculated according to standard curve equation, respectively. The results are that thepotassium cyanide-barbituric acid method for determining cotinine in rat urine wasconsistent with the pharmacokinetical research. The standard control of nicotine and theoutput of nicotine in rat had a well linear relation, and could estimate the absorbed contentof nicotine in the blood of rats according to the output of the cotinine. |
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