聚L-乳酸包裹阿霉素颗粒的实验研究及治疗骨肿瘤的初步临床观察  

Experimental study of poly L-lactic acid packed adriamycin granule and its preliminary clinical observation on bone tumor treatment

作　　者：宋建民[1] 田义杰[1] 李德杏[1] 

机构地区：[1]甘肃省肿瘤医院骨与软组织肿瘤科,甘肃兰州730050

出　　处：《兰州大学学报（医学版）》2005年第3期16-20,共5页Journal of Lanzhou University（Medical Sciences）

摘　　要：目的为边缘或瘤内切除的骨肿瘤瘤腔寻找一种既可以充填,又可以缓慢释放抗肿瘤药物、减少局部肿瘤复发的瘤腔充填材料。方法合成聚L-乳酸,包容阿霉素制成颗粒,检测其体外释药特性。用家兔做动物毒理试验,在股骨髁上钻孔,将定量药物颗粒填充在骨腔中,对照组只钻孔不放药,用荧光光度法测定血药含量,检测肝肾功能。对13例骨肿瘤术后瘤腔用聚L-乳酸阿霉素颗粒与骨水泥以1/2比例混合后充填,与7例单用骨水泥充填者对照,观察手术部位与全身的毒副反应。结果合成的聚L-乳酸粘分子量为10550,包裹阿霉素颗粒的阿霉素含量为2.87%。,体外缓释时间在25d以上。试验动物血液内未测到阿霉素含量,对动物肝肾功能无影响。聚L-乳酸阿霉素颗粒在充填的骨骼局部,早期造成骨髓组织坏死、变性,后期纤维组织增生,并在局部逐渐降解。临床应用早期强度好,后期也未见局部骨折。所有病例切口均甲级愈合,无明显的全身损害表现及类似化疗时的副作用出现,肿瘤复发较对照组晚。结论聚L-乳酸包裹阿霉素颗粒有较好的药物缓释性,对机体无明显的毒副作用,与骨水泥混合充填骨肿瘤术后残腔,操作方便,有较好的生物力学强度,可有效控制肿瘤的复发。Objective To search a filling anti-tumor agent that can be released slowly in the tumor cavity after bone tumor operation. Methods poly L-lactic acid（PLA） packed adriamycin granule was made by PLA and adrianlycin, and its release characteristics were detected in vitro. Rabbits were used for animal toxicity test by drilling a hole in rabbit supracondyle of femur, and filling fixed quantity of granule into bone cavity in experimental group, no granule was filled in control group. Blood-drug concentration was detected by fluorescent photometry, and liver as well as kidney function was examined. To take a pathological study at different time after operation, 13 cases of tumor cavity after bone tumor operation were filled with a mixture of PLA-packed adriamycin and PMMA in the proportion of 1 to 2, and 7 cases were filled only with PMMA for control to observe toxic and side reactions at operative sites and in the whole bodies. Results The molecular weight of PLA is 10 550 and the content of adriamycin in the granule is 2.87%0, its release time was above 25 days in vitro. No adriamycin in rabbit blood or liver and kidney function damages was detected. PLA-packed adriamycin granule caused bone marrow tissue necrosis and degeneration at early stage and fibrous tissue proliferation and degradation at late stage in local filling areas. In the clinical study, the intensity of bone that filled with the granule and PMMA was good at early stage and no local bone fracture occurred at late stage. All incisions reached A-level healing, and no obvious systemic damage and side effects similar to chemotherapy were observed, tumor recurrence was also delayed when compared with control. Conclusion PLA-packed adriamycin granule has good slow release effects to human body. When mixed with PMMA convenient to operate, has good biological intensity property and has no obvious toxic and side to fill cavity after bone tumor operation, it is and can suppress tumor recurrence effectively.

关 键 词：阿霉素 聚L-乳酸 骨肿瘤 治疗 聚L-乳酸 阿霉素 骨肿瘤 颗粒 临床观察 包裹 局部肿瘤复发 实验研 生物力学强度 

分 类 号：R318.08[医药卫生—生物医学工程] R979.1[医药卫生—基础医学]