目的 研究醋酸齊考諾肽重復鞘內(nèi)注射給藥的局部刺激性，為鞘內(nèi)注射制劑的局部刺激性評價提供參考。方法 16只新西蘭兔，隨機分為對照組（生理鹽水）和醋酸齊考諾肽組，每組8只，雌雄各半，腰椎穿刺鞘內(nèi)注射給藥，給藥濃度為100 μg/mL，體積為50 μL/只，每天1次，連續(xù)給藥7 d，恢復14 d。每天觀察動物一般癥狀，并于末次給藥后2 d，每組處死4只動物進行剖檢，取注射部位及前段和后段處腰椎和脊髓進行組織病理學檢查及刺激性評價，剩余動物于末次給藥后14 d剖檢并進行刺激性評價。結果 對照組1只動物于給藥第3天麻醉后死亡，其余動物在給藥及恢復期間未見明顯異常癥狀；末次給藥后2、14 d，各組動物組織病理學檢查均未見明顯的鞘內(nèi)刺激性反應；末次給藥后2 d，注射點見可逆的輕微機械性損傷。結論 本試驗條件下，與對照組比較，未見醋酸齊考諾肽對腰椎、硬脊膜和脊髓的局部刺激性作用，新西蘭兔可作為鞘內(nèi)注射制劑的局部刺激性評價模型。

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.