席焱海++++何海龙++李坤++++++刘希麟++薛敏涛+++++徐宁+++叶晓健

    [摘要] 目的 研究阶梯缓释抗结核纳米人工骨复合体(β-TCP/INH-RFP-PCL/SM-SA)的生物安全性。 方法 对β-TCP/INH-RFP-PCL/SM-SA复合体进行体外噻唑蓝(MTT)细胞毒性实验，动物体内急性全身毒性实验、原发性皮肤刺激实验、皮内刺激实验和致敏实验，并设置对照组进行比较。 结果 β-TCP/INH-RFP-PCL/SM-SA复合体MTT细胞毒性实验显示人工骨材料组细胞存活率在95%以上，细胞毒性1级。人工骨复合材料浸取液不引起豚鼠过敏。原发性皮肤刺激实验和皮内刺激实验均提示复合材料对兔皮肤、皮内无刺激反应。小鼠尾静脉注射后未出现明显全身毒性反应。 结论 β-TCP/INH-RFP-PCL/SM-SA无明显细胞毒性，具有良好的细胞相容性，在应用过程中能够降低直接使用抗结核药物所带来的生物毒性。动物全身毒性反应、皮肤/内刺激反应和急性过敏反应提示该材料具有良好的生物安全性。

    [关键词] 结核；药物缓释；纳米；生物安全性

    [中图分类号] R943[文献标识码] A[文章编号] 1673-7210(2014)06(c)-0022-05

    Biological security of ladder-sustained-release anti-TB drugs artificial composite bone

    XI Yanhai HE Hailong LI Kun LIU Xilin XUE Mintao XU Ning YE Xiaojian▲

    Department of Spinal Surgery, Orthopaedic Hospital of Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai 200003, China

    [Abstract] Objective To investigate the biological security of ladder-sustained-release anti-TB drugs artificial composite bone (β-TCP/INH-RFP-PCL/SM-SA). Methods MTT toxicity test, acute systemic toxicity test, intracutaneous irritation test and skin sensitization in stimulation were performed in the ladder-sustained-release anti-TB drugs artificial composite bone. The results were compared with control group. Results MTT toxicity test showed that the survival rate of bone cells in artificial materials was more than 95% and cytotoxicity was on grade 1. Artificial bone composite material liquid did not cause allergic reaction in guinea pig. Primary skin irritation experiments and intradermal stimulation experiment suggested that composite materials to rabbit skin and intracutaneous no stimulation reaction. No obvious systemic toxic reaction was found in mice after intravenous injection. Conclusion There is no MTT cytotoxicity in the ladder-sustained-release anti-TB drugs artificial composite bone. It can reduce the biological toxicity of anti-TB drugs and will not cause systemic toxic reaction, skin/hypodermic stimulation reactions and acute allergic reaction. It has good cell compatibility and biological security. ......