醋酸齐考诺肽重复鞘内给药的局部刺激性研究  

Local irritation study of repeated lumbar intrathecal injection of Ziconotide Acetate

作　　者：宋莹[1] 付新录[1] 兰天龙[2] 杨学敏 麦焕娣 聂涛 黄芝瑛[4] 邱玉文[1] 

机构地区：[1]中山大学实验动物中心,广东广州510006 [2]天津药物研究院新药评价有限公司,天津300301 [3]深圳翰宇药业股份有限公司,广东深圳518035 [4]中山大学药学院,广东广州510006

出　　处：《药物评价研究》2017年第1期54-58,共5页Drug Evaluation Research

摘　　要：目的研究醋酸齐考诺肽重复鞘内注射给药的局部刺激性,为鞘内注射制剂的局部刺激性评价提供参考。方法 16只新西兰兔,随机分为对照组(生理盐水)和醋酸齐考诺肽组,每组8只,雌雄各半,腰椎穿刺鞘内注射给药,给药浓度为100μg/m L,体积为50μL/只,每天1次,连续给药7 d,恢复14 d。每天观察动物一般症状,并于末次给药后2 d,每组处死4只动物进行剖检,取注射部位及前段和后段处腰椎和脊髓进行组织病理学检查及刺激性评价,剩余动物于末次给药后14 d剖检并进行刺激性评价。结果对照组1只动物于给药第3天麻醉后死亡,其余动物在给药及恢复期间未见明显异常症状;末次给药后2、14 d,各组动物组织病理学检查均未见明显的鞘内刺激性反应;末次给药后2 d,注射点见可逆的轻微机械性损伤。结论本试验条件下,与对照组比较,未见醋酸齐考诺肽对腰椎、硬脊膜和脊髓的局部刺激性作用,新西兰兔可作为鞘内注射制剂的局部刺激性评价模型。Objective To study the local irritation of repeated intrathecal injection of Ziconotide Acetate, and to provide reference for irritancy evaluation of intrathecal injection. Methods Sixteen New Zealand rabbits were assigned into two groupsat random： Control group and Ziconotide Acetate group, eight animals each group. Totally 50 μL saline or Ziconotide Acetate （100 μg/mL） were administrated by repeated lumbar intrathecal injection once daily for 7 d. Animal behavior was observed every day, and four animals in each group were sacrificed 2 d later after the last injection, the lumbar spinal cord was removed for histopathological examination and irritancy evaluation. The remaining animals were sacrificed for irritancy evaluation 14 d later after the last injection. Results Only one animal died after anesthesia on day three in saline group, while no obvious adverse reactions were observed in other rabbits during the entire study, and no intrathecal irritant reactions of histopathological examination were found in both groups. The reversible minor mechanical damage was observed at the injection point, 2 d after the last administration. Conclusion For 7 d repeated lumbar intrathecal injection in rabbits, no intrathecal irritant reactions observed in Ziconotide group, and the New Zealand rabbit could be used as a local irritation evaluation model.

关 键 词：醋酸齐考诺肽 新西兰兔 鞘内注射 重复给药 局部刺激性 

分 类 号：R965[医药卫生—药理学]