摘要
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 determine the acute and chronic toxicity of ginkgolide B injection to provide safety basis for the clinical studies. Method： Ginkgolide B injection was administered to mice by IV to assess the acute toxicity, and LDs0 and 95% confidence limit were calculated by SPSS. Twenty-six dogs were randomly divided into 4 groups, namely control group and low-dose, mid-dose and high-dose groups. The dogs were administered 0.9% sodium chloride injection ,2,13 and 80 mg·kg ^-1 ·d ^-1 ginkgolide B injection by in- travenous drip for 3 months, respectively. Toxicological assessments included such indices as general conditions,body weight, body tem- perature, electrocardiography, ophthalmologic examinations, clinical pathology （ coagulation, hematology, serum chemistry and urinaly- sis）, relative organ weight to body weight and histopathological examinations. Result： For acute toxicity study, when the dose of ginkgol- ide B injection was 500,425,361,307 and 261 mg. kg^-1 , the number of dead mice was 8,4,2,2 and 2, respectively. No mouse was found dead at the dose of 222mg·kg^-1. At the end of the administration of ginkgolide B injection by intravenous drip for 3 months,par- tial tubular epithelium vacuolar degeneration or granular degeneration were shown in the kidneys of all animals. Alveolar or alveolar sep- tum macrophage proliferation was observed in lung edges of 4 dogs in high-dose group. Those changes were not found in the animals at the recovery phase. The other indices were without significant change. Conclusion： LDso and 95% confidence limit of ginkgolide B in- jection was 424 mg.kg-1 and 371-552 mg.kg^-1 ,respectively when administered to mice via IV. The NOAEL of ginkgolide B injection was 13 mg·kg^-1·d^-1 when administered to dogs via intravenous drip for 3 months. Kidney and lung reversible toxicities were observed at the dose of 80 mg. kg - l. d ^-1.
出处
《中国药师》
CAS
2011年第11期1629-1632,共4页
China Pharmacist
