骨靶向帕珠沙星的制备及其体外研究

Synthesis and in vitro experiments of bone-targeted pazufloxacin

目的制备以双膦酸为骨导向物质，以氧化葡聚糖为中间体的骨靶向帕珠沙星复合物，并作相关体外亲骨性和抗菌活性研究。方法将葡聚糖（T-40）用高碘酸钠氧化为氧化葡聚糖，再依据希弗碱合成原理，分别将双膦酸和帕珠沙星枝接于氧化葡聚糖上，制备出骨靶向帕珠沙星复合物，并将各步产物进行红外和核磁共振检测表征。运用羟基磷灰石吸附试验，测定骨靶向药物的体外亲骨性；用微量肉汤稀释法测定大肠埃希菌、铜绿假单胞菌、金黄色葡萄球菌3株标准菌株的最小抑菌浓度（MIC），确定其体外抗菌活性。结果成功合成具有骨靶向性的帕珠沙星抗生素，其载药量为4．65％；羟基磷灰石吸附率为87．91％；对3株标准菌株的MIC均高于原料药帕珠沙星。结论合成的骨靶向性帕珠沙星，具有良好的体外亲骨性，但其体外抗菌活性有所降低。

Objective To prepare the bone-targeted pazufioxacin complex with the diphosphonic acid as bone-oriented material and the oxidized dextran as an intermediate, and make research on the affini- ty for bone in vitro and the antibacterial activity about the complexes. Methods Dextran （T-40） was oxi- dized to oxidized dextran by sodium periodate oxidation of dextran, and then diphosphonic acid and pazu- floxacin were combined with oxidized dextran respectively based on the synthesis principle of Schieffer base. The bone-targeted pazufloxacin complex was prepared successfully, and the products for each step were characterized by infrared and nuclear magnetic resonance. The adsorption test of hydroxyapatite （HA） was used to evaluate the affinity of bone-targeted drugs for bone in vitro. Micro-broth dilution method was used to determine the minimum inhibitory concentration （MIC） of pazufloxacin complex against three standard strains （Eseheriehia coli, Pseudomonas aeruginosa and Staphylococcus aureus ）. Results The bone-targeted pazufloxacin complex was synthesized successfully. Its capacity of drug loading was 4. 65%, the rate of HA adsorption was 87.91%, and its MICs against the three standard strains were higher than pazufloxacin. Condusion The bone-targeted pazufloxacin had strong affinity for bone in vitro, but its external antibacterial activity was decreased.