纤维蛋白凝胶包裹的万古霉素藻酸盐微球的制备与优选  

Preparation and optimization of fibrin-gel-coated vancomycin alginate beads

作　　者：侯天勇[1] 吴雪晖[1] 许建中[1] 李强[1] 冯江华[1] 

机构地区：[1]第三军医大学附属西南医院骨科、全军矫形外科中心,重庆

出　　处：《中华创伤杂志》2008年第6期470-474,共5页Chinese Journal of Trauma

基　　金：国家高新技术研究发展计划重大专项基金资助项目（2006AA02A122）;重庆市重点科技攻关资助项目（2006AB5008）

摘　　要：目的制备和优化纤维蛋白凝胶包裹的万古霉素藻酸盐微球（fibrin-gel-coated vancomycin alginate beads，FG-Vanco-AB），探讨其在骨科抗感染治疗中的可能应用。方法应用滴注法制备万古霉素藻酸盐微球，通过分别改变万古霉素和藻酸盐溶液的浓度，优选万古霉素含量高的微球；然后用不同浓度纤维蛋白凝胶包裹，通过检测各组万古霉素有效的释放时间来筛选适当包裹微球。结果随着万古霉素和藻酸盐溶液浓度的升高，微球中的万古霉素含量增高，16％藻酸盐和50mg/ml万古霉素等体积混合液制备的微球中万古霉素含量最高，达（27．36±0．90）％；在前述微球的基础上，用不同浓度纤维蛋白包裹的微球的缓释实验显示，75mg／ml纤维蛋白包裹的微球释放的万古霉素的浓度达到可有效杀灭金黄色葡萄球菌的天数为19d。结论优选后的FG-Vanco-AB可达到有效杀菌浓度的释放天数显著延长，增加了临床应用的可能性。Objective To prepare and optimize fibrin-gel-coated vancomycin alginate beads （FG-Vanco-AB） and investigate their possible use in treatment of osteomyelitis or prevention of infection. Methods Vancomycin alginate beads were produced by dropping vancomycin and alginate mixed liquor into calcium chloride solution. Beads including high vancomycin content were prepared and chosen by optimizing different concentrations of vancomycin solution and alginate solution. These beads were coated with fibrin gel formed by different concentrations of fibrin and the same concentration thrombin. The optimized beads were selected based on available release time, when vancomycin in medium could kill Staphylococcus aureus （ATCC25923）. Results Higher content of vancomycin in bead resulted in increase of vancomycin concentration and alginate concentration in mixed liquid. The highest vancomycin content beads were prepared by 16% alginate and 50 mg/ml vancomycin, up to （27.36 ±0.90）%. The further results showed that vancomycin concentrations from beads coated with fibrin at 75 mg/ml and thrombin at 400 IU/ml could kill Staphylococcus aureus and remained above the breakpoint sensitivity for 19 days. Conchmion The available release time is prolonged, and the possibility of clinical use is conspicuously increased after vancomycin beads are optimized by adjusting the rate of mixed component and fibrin gel coat.

关 键 词：抗感染药 局部 迟效制剂 纤维蛋白组织黏着剂 骨组织感染 

分 类 号：R94[医药卫生—药剂学]