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出 处:《广东医学》2010年第24期3160-3163,共4页Guangdong Medical Journal
基 金:广东省重点实验室建设项目(编号:2060204);全军医学科学技术研究"十一五"计划第二批课题专项资助(编号:08Z010)
摘 要:目的研制复合抗肿瘤自制珊瑚羟基磷灰石人工骨并评价其理化性能。方法通过水热反应制备珊瑚羟基磷灰石人工骨,通过真空冷冻干燥等处理将顺铂载入形成复合抗肿瘤自制珊瑚羟基磷灰石人工骨(com-posite coralline hydroxyapatite,CCHA),扫描电镜及能谱分析等分析复合人工骨断面的孔隙、顺铂的含量及分布情况,将复合人工骨浸入模拟体液取得不同时间浸提液并植入大鼠肌袋内,利用高效液相色谱法(high performanceliquid chromatography,HPLC)检测不同时期的体外缓释试验浸提液、体内缓释试验肌肉组织及血液中顺铂的浓度。结果 CCHA的孔隙结构未改变,孔隙内顺铂分布均匀,HPLC结果示顺铂和内标液的保留时间分别为4.6 min和7.5 min,两者分离效果良好。体外缓释液中前2周顺铂出现快速释放,体外浸提液中顺铂的浓度极高[2周时浓度为(753.01±64.89)μg/mL;]至12周其顺铂浓度仍达到(134.54±9.88)μg/mL。动物植入CCHA后局部较长时间内可维持较高顺铂浓度,随着时间的延长及与人工骨的距离增加,局部的顺铂浓度呈下降趋势。结论 CCHA具有良好的缓释效能,可在局部维持一定时间的高药物浓度。Objective To prepare and evaluate the physical and chemistry performance of self-made anti-tumor composite coralline hydroxyapatite(CCHA). Methods The coralline hydroxyapatite(CHA) was prepared using hydrothermal exchange reaction.Cisplatin was impregnated into CHA by vacuum freeze-drying techniques.The pores of CHA and CDDP concentration and distribution were analyzed by scanning electron microscopy and spectrum analysis.The leaching liquor of CCHA was collected and measured by high performance liquid chromatography at different intervals during 8 weeks in vivo and in vitro,respectively. Results(1)CDDP was well-distributed in CHA pores in electron microscopy.(2)High performance liquid chromatography(HPLC) showed that the retention times of cisplatin and internal standard were 4.6min and 7.5min,respectively.(3)In the first two weeks of in vitro desorption study,CDDP released rapidly from CDDP-CHA complex.The concentration of CDDP in leaching liquor was extremely high and maintained at the level of(134.54±9.88)μg/mL after 12 weeks.(4) CDDP-CHA complexes produced high CDDP concentration in local regions of implanted SD rats and decreased following time and distance-dependent manners.(5) Serum CDDP concentration remained low(less than 17 μg/mL) in implanted rats,significantly lower than that of local tissue. Conclusion The CCHA has good sustained release function and provides sufficient focal CDDP concentration.
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