盐酸椒苯酮胺对大鼠和Beagle犬的急性毒性实验研究
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篇名: 盐酸椒苯酮胺对大鼠和Beagle犬的急性毒性实验研究
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摘要: 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。
ABSTRACT: OBJECTIVE: To investigate acute toxicity of piperphentonamine hydrochloride (PPTA) in rats and Beagle dogs, and to calculate maximum dosage and evaluate its safety. METHODS: SD rats were given relevant medicine via ig or iv, at a single dose of 50   mg/kg, every 4-6 h, for consecutive 3 times, 150 mg/kg in total; after 14 d treatment, the toxicity reaction and body weight of rats were observed in PPTA group (n=40) and solvent control group (n=20). Beagle dogs were given PPTA ivgtt, at maximal single dose of 200 mg/kg; after 14 d of treatment, Beagle dogs of PPTA group (n=4) and solvent control group (n=3) were observed in respects of general physiological index, body weight, body temperature, ECG index, blood pressure, plasma electrolyte, urine, ophthalmology and pathological index, etc. RESULTS: There was no obvious abnormality in rats after ig administration of PPTA. One-off action instability occurred after iv within minutes; no abnormality was found for 14 days; the increase of body weight of rats in treatment groups was normal. Transient conjunctival congestion, nausea and vomiting, salivation, mild edema eyelids and rear limb weakness were observed in Beagle dogs during dosing; only one Beagle dog suffered from hematuria caused by hemorrhage of bladder. 14 d after medication, there was no statistical significance in body weight and temperature of Beagle dogs between treatment groups and solvent control group (P>0.05). No abnormal changes due to drug toxicity reaction were observed. CONCLUSIONS: LD50 values of PPTA in rats via ig and iv are over 150 mg/kg. Beagle dogs did not died at the single dose of 200 mg/kg PPTA, ivgtt. The abnormal signs of animals may be the side effects of PPTA. The main toxic reaction of PPTA may be hemorrhage of bladder and other.
期刊: 2016年第27卷第10期
作者: 李健,李茹冰,张强,陈新,尹雁,朱晋辉,樊鸿浩,邓乐君,付岩霖,李伟达
AUTHORS: LI Jian,LI Rubing,ZHANG Qiang,CHEN Xin,YIN Yan,ZHU Jinhui,FAN Honghao,DENG Lejun,FU Yanlin,LI Weida
关键字: 盐酸椒苯酮胺;急性毒性;大鼠;Beagle犬;最大给药量
KEYWORDS: Piperphentonamine hydrochloride; Acute toxicity; Rats; Beagle dogs; Maximal dose
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