论文部分内容阅读
目的:研究银杏内酯B注射液的急性毒性和长期毒性,为临床试验提供安全性依据。方法:以静脉注射进行小鼠急性毒性试验,计算半数致死量(LD_(50))及95%置信限;并将26只Beagle犬随机分为4组(对照组、低、中、高剂量组),分别静脉滴注生理盐水和2、13、80mg·kg~(-1)·d~(-1)注射用银杏内酯B。连续给药3个月,观察动物一般状况、体质量、体温、心电图、眼科、尿常规、血液学、血液生化、脏器质量系数及病理组织学改变。结果:注射用银杏内酯B单次给药500,425,361,307,261mg·kg~(-1)分别死亡8、4、2、2、2只小鼠,222mg·kg~(-1)未见小鼠死亡;对犬静脉滴注给药3个月,给药末,高剂量组全部犬肾脏,部分肾小管上皮细胞颗粒变性、空泡变性,4例肺脏边缘肺泡腔及肺泡膈内散在有巨噬细胞增生。恢复期无此变化。其他各项指标未见显著毒性反应。结论:小鼠静脉注射银杏内酯B的LD_(50)(95%置信限)为424mg·kg~(-1)(371～552mg·kg~(-1));对犬静脉滴注3个月,13mg·kg~(-1)·d~(-1)为未观察到有害作用剂量(NOAEL),80mg·kg~(-1)·d~(-1)引起肺脏和肾脏的可逆性毒性反应。
Objective: To study the acute toxicity and long-term toxicity of ginkgolide B injection and provide a safety basis for clinical trials. Methods: Acute toxicity test in mice was performed by intravenous injection. LD50 and 95% confidence limits were calculated. 26 Beagle dogs were randomly divided into 4 groups (control group, low, medium and high dose groups) ) Were injected intravenously with normal saline and ginkgolide B at 2, 13 and 80 mg · kg -1 d -1, respectively. The animals were continuously administered for 3 months. The general condition, body weight, body temperature, electrocardiogram, ophthalmology, urine routine, hematology, blood biochemistry, organ quality factor and histopathological changes were observed. Results: Eight, four, two, two and two mice were killed at doses of 500, 425, 361, 307 and 261 mg · kg -1, respectively. No mice died at 222 mg · kg -1. The dogs were given intravenous drip for 3 months. At the end of the experiment, all the canine kidney and some renal tubular epithelial cells were degenerated and vacuolar degeneration in all the dogs in the high-dose group. In 4 cases, macrophage hyperplasia was found in the alveolar cavity and alveolar septum . No such changes during the recovery period. No other indicators of significant toxicity. Conclusions: The LD_ (50) (95% confidence interval) of intravenous ginkgolide B in mice was 424 mg · kg -1 (371 ~ 552 mg · kg -1) Month, 13 mg · kg -1 · d -1 were the NOAEL and 80 mg · kg -1 · d -1, respectively, which caused the reversibility of lung and kidney Toxic reaction.