自制抗肿瘤珊瑚羟基磷灰石人工骨的制备及性能评价

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 (composite 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及植入大鼠肌袋内，利用高效液相色谱法(high performance liquid 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，利用高效液相色谱法检测体外浸提液、动物静脉血及组织匀浆液中的顺铂浓度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?g/mL)；至12周其顺铂浓度仍达到(134.54±9.88)?g/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高药物浓度。

Preparation and evaluation of self-made anti-tumor composite coralline hydroxyapatite

Abstract: Objective To prepare and evaluate the physical and chemistry performance of self-made composite anti-tumor coral hydroxyapatite(CCHA) Methods The coral hydroxyapatite(CHA) was made by hydrothermal exchange. Cisplatin was impregnated into CHA by vacuum freeze-drying techniques. The pore of CHA and the content and distribution of CDDP were analyzed by scanning electron microscope and spectrum analysis.The leaching liquor of CCHA was collected and was detected by high performance liquid chromatography at different intervals during 8 weeks in vivo and vitro. Result 1. Electron microscope showed CDDP were well-distributed in CHA pores.2.High performance liquid chromatography(HPLC) showed that the retention times of cisplatin and internal standard are 4.6min and 7.5min respectively. 3. In the first two weeks of in vitro desorption study, CDDP release rapidly from CDDP-CHA complex, the concentration of CDDP in leaching liquor is extremely high and still have 134.54±9.88µg/ml after 12 weeks. 4.After implantation into SD rats, CDDP-CHA complexes produced high CDDP concentration in local regions. With time passing and distance increasing, the concentrations of CDDP decreased. 5. When implantated into SD rats, the concentration of CDDP in blood stream remained at a low level, less than 17ug/ml, much lower than that in local tissue. 6. CDDP-CHA complex implantation has no harmful effects on all other organs, showed by histological section. Conclusions The CCHA had good sustained releasee function.