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目的:观察盐酸椒苯酮胺(PPTA)对大鼠和Beagle犬的急性毒性反应,计算最大给药量并评价其安全性。方法:对SD大鼠分别ig和iv给药,单次剂量为50 mg/kg,间隔4~6 h,连续3次,总剂量为150 mg/kg,给药后连续14 d观察PPTA给药组(n=40)和溶剂对照组(n=20)大鼠毒性反应及体质量等。对Beagle犬单次ivgtt PPTA最大给药剂量200 mg/kg,给药后连续14 d观察PPTA给药组(n=4)和溶剂对照组(n=3)Beagle犬的一般生理指标、体质量、体温、心电指标、血压、血浆电解质、尿液、眼科和病理学指标等。结果:大鼠经ig给药后未见明显异常表现,但iv给药数分钟内出现一过性的行动不稳,连续观察14 d均未见异常情况;给药组大鼠体质量均增长正常。Beagle犬给药过程出现一过性结膜充血、恶心呕吐、流涎、眼睑轻微水肿和后肢无力,有1只出现膀胱出血致尿血的现象;给药后14 d内给药组犬体质量与体温变化情况与溶剂对照组比较,差异无统计学意义(P>0.05),其他各项指标均未观察毒性反应相关的异常改变。结论:大鼠ig和iv给予PPTA的半数致死量(LD50)值均大于150 mg/kg;Beagle犬单次ivgtt给予PPTA 200 mg/kg未导致犬死亡,给药后所出现的异常体征为该药的毒副反应,膀胱出血等可能是该药主要的毒性反应。
Objective: To observe the acute toxicity of piperphentonamine hydrochloride (PPTA) in rats and Beagle dogs, calculate the maximum dose and evaluate its safety. Methods: The SD rats were administered with ig and iv respectively at a single dose of 50 mg / kg for 4 ~ 6 h at 3 consecutive doses for a total of 150 mg / kg. The administration of PPTA Group (n = 40) and solvent control group (n = 20), the toxicity and body weight of rats. The maximum dose of iv iv PPTTA in Beagle dogs was 200 mg / kg, and the general physiological parameters of Beagle dogs in PPTA group (n = 4) and solvent control group (n = 3) , Body temperature, ECG, blood pressure, plasma electrolytes, urine, ophthalmology and pathology indicators. RESULTS: No significant abnormalities were observed after ig administration in rats, but transient instability appeared within a few minutes after iv administration, and no abnormalities were found after 14 consecutive days of administration. The body weight of rats in the administration group increased normal. Beagle dogs had transient conjunctival hyperemia, nausea, vomiting, salivation, mild eyelid edema and hindlimb weakness during the administration of Beagle dogs. One case had hemorrhage caused by bladder hemorrhage. Within 14 days after administration, the body mass and body temperature Compared with the solvent control group, there was no significant difference between the two groups (P> 0.05). No abnormal changes related to toxicity were observed in other indexes. CONCLUSION: The LD50 values of ig and iv given to PPTA in rats are both higher than 150 mg / kg. Beagle dogs given single ivgtt with PPTA 200 mg / kg did not cause death in dogs. The abnormal signs after the administration Drug toxicity, bladder hemorrhage may be the main toxicity of the drug.