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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 induced by repeated administration of xiconotide acetate intrathecal injection and to provide a reference for the evaluation of the local irritation of intrathecal injection. Methods Twenty-six New Zealand white rabbits were randomly divided into control group (normal saline) and ziconotide acetate group (n = 8 each), male and female were divided into two groups. The lumbar puncture was injected intrathecally with the concentration of 100μg / 50μL / only, once a day, continuous administration 7d, recovery 14d. The animals were observed daily for symptoms. At 4 days after the last administration, 4 animals were killed in each group for necropsy. The lumbar and spinal cord at the injection site, anteroposterior and posterior segments were examined for histopathology and irritation. The remaining animals The last 14 days after the last dose of autopsy and irritation evaluation. Results One animal died in the control group on the third day after administration, and the other animals showed no obvious abnormal symptoms during the administration and recovery. No significant histopathological examination was found on the 2 and 14 d after the last administration Of the intrathecal irritant reaction; 2 d after the last administration, the injection point to see the reversible mild mechanical damage. CONCLUSIONS: Compared with the control group, no local irritation effect of ziconotide on lumbar vertebrae, spinal dura and spinal cord was observed in this study. New Zealand rabbit can be used as a local irritation model for intrathecal injection.