摘要
目的:比较去甲斑蝥素普通剂型和缓释剂型对小鼠的急性毒性,证实缓释剂型的减毒作用。方法:选择药物缓释辅料泊洛沙姆407,将去甲斑蝥素制成注射用缓释剂型,分别观察普通剂型和缓释剂型两种不同剂型去甲斑蝥素小鼠尾静脉、腹腔、肝脏和肌肉注射时的急性毒性反应,并计算半数致死量(medianlethaldose,LD50)。结果:两组小鼠毒性反应相似,但缓释制剂组反应出现时间滞后约4h;去甲斑蝥素普通制剂小鼠尾静脉注射LD50为12.6mg/kg;缓释制剂组腹腔、肝脏和肌肉注射时的LD50分别为19.9、19.1和20.9mg/kg,明显高于普通制剂组的13.0、13.1和15.1mg/kg。结论:去甲斑蝥素缓释剂型可能通过缓慢释放药物,降低峰值血药浓度,从而减轻毒性。
Objective： To compare the acute toxicity of common injection and sustained-release preparation of norcantharidin for mice so as to identify the attenuation of the sustained-release preparation of norcantharidin.
Methods： The poloxamer 407 was used as a sustained-release vehicle for topical administration of norcantharidin, and the acute toxicity of mice treated with common injection and sustained-release preparation of norcantharidin was observed. The median lethal dose （LD50） was calculated by Bliss software.
Results： The symptoms of mice were similar between the two groups, but the appearance of symptoms in norcantharidin/poloxamer 407 group was 4 hours later than that in norcantharidin group. The LD50 of norcantharidin administered through vein injection was 12.6 mg/kg. The LD50 of norcantharidin/poloxamer 407 administered through intraperitoneal injection, intrahepatic injection and intramuscular injection were 19. 9, 19. 1 and 20. 9 mg/kg, respectively, and the LD50 of the common preparation were 13. 0, 13. 1 and 15. 1 mg/kg, respectively.
Conclusion： The norcantharidin/poloxamer 407 is less toxic than the equivalent dose of norcantharidin, mainly because norcantharidin/poloxamer 407 may release norcantharidin sustainedly, thus reducing norcantharidin concentration in blood.
出处
《中西医结合学报》
CAS
2007年第1期74-77,共4页
Journal of Chinese Integrative Medicine
基金
上海市科学技术委员会中药现代化研究科研基金资助项目(No.03DZ19506)
关键词
缓释制剂
泊洛沙姆407
急性毒性实验
sustained-release preparations
poloxamer 407
acute toxicity tests
