左氧氟沙星骨植入缓释片的制备、体内释放性能及局部安全性研究  

Preparation,releasing feature and local biological safety evaluation of bone implanted sustained-releasing levofloxacin tablets

作　　者：修涵[1] 曹洪[2] 王健飞[1] 平洁[1] 刘莲[1] 陈廖斌[2] 汪晖[1] 

机构地区：[1]武汉大学基础医学院药理学系,武汉430071 [2]武汉大学中南医院骨科,武汉430071

出　　处：《中国新药杂志》2013年第18期2190-2194,共5页Chinese Journal of New Drugs

基　　金：武汉市首届优势学科带头人计划(20065006131-02)

摘　　要：目的：制备左氧氟沙星骨植入缓释片受试制剂，并进行初步的药理毒理学评价。方法：采用溶剂挥发法制备受试制剂。不同时间点检测植入动物体内的受试制剂中左氧氟沙星释放浓度。进行稳定性试验、溶血性实验和局部刺激性实验。结果：受试制剂质地均匀紧实、表面平整光滑。左氧氟沙星的骨释放量为170．8μg·g-1，血浆浓度为4．43μg·mL-1。高温条件下10d后受试制剂重量损耗0．369％，左氧氟沙星含量变化率1．558％，高湿条件下10d后吸湿增重2．071％、左氧氟沙星含量变化率3．738％。受试制剂无溶血反应发生，植入组织局部未见炎性细胞及异型细胞，无局部刺激性。结论：缓释片制备方法可行，体内释放效果能满足4～6周的临床需要，其稳定性好，无局部刺激性。Objective： To prepare the bone implanted sustained-releasing levofloxacin tablets, and to pre- liminarily evaluate their pharmacological and toxicological properties. Methods： Solvent evaporation method was employed to prepare the testing tablets. The release characteristics in the rabbit body were examined by detecting the concentrations of levofloxaein in bone and plasma at different time points. Thereafter, a series of studies inclu- ding stability test, hemolysis test and local safety test were performed. Results： The test tablets presented homoge- neous compaction and smooth surface. The average concentration of levofloxacin released from the test tablets to bone was 170.8 μg.g-1, and the average plasma concentration was 4.43 μg.mL-1. Under the high-temperature conditions, the weight loss of the test tablets was 0. 369% , and the change rate of levofloxacin content was 1. 558%. Under the high-humidity conditions, the weight increasing ratio of the test tablets was 2. 071% , and the change rate of levofloxacin content was 3. 738%. No hemolytic reaction was observed in hemolysis test. The inflam- matory cells and atypical cells were absence, suggesting no local irritation. Conclusion： Preparation of the sus- tained-releasing tablets is feasible. The effect of the in vivo release meets the 4- to 6-week clinical treatment needs, and the tablets also show better stability and no local irritation.

关 键 词：左氧氟沙星 消旋聚乳酸 缓释 稳定性 局部刺激性 

分 类 号：R943.4[医药卫生—药剂学]