万古霉素磷酸钙骨水泥与万古霉素聚甲基丙烯酸甲酯骨水泥体外洗脱特性的比较

发布时间：2018-09-19 16:57

【摘要】：背景：慢性骨髓炎由于其病情复杂、病程长、局部骨质缺损、容易复发等特点，一直是困扰骨科医生的医学难题。根据慢性骨髓炎的病理变化及治疗原则，以病灶局部清创、敏感抗生素的选择应用、修复病变区域的骨缺损为指导思想，临床医生进行了诸多尝试。局部使用聚甲基丙烯酸甲酯（PMMA）水泥为载体释放高剂量抗生素连同应用全身性抗生素，是现阶段临床治疗慢性骨髓炎的标准方案。然而，PMMA具有水泥聚合反应过程中加热、需二次手术取出等缺点。最近，磷酸钙骨水泥（CPC）已被用作骨替代和扩增，，并在聚合过程中不发热、对加载药物活性无影响。对磷酸钙骨水泥(CPC)加载万古霉素（VCM）与聚甲基丙烯酸甲酯骨水泥(PMMA)加载万古霉素(VCM)释放药物浓度、时间的差异,国内仍未有明确研究。目的: 对比磷酸钙骨水泥(CPC)加载VCM与聚甲基丙烯酸甲酯骨水泥(PMMA)加载VCM释放药物浓度、时间的差异，为临床应用提供实验基础。方法：测试样本包括磷酸钙骨水泥或聚甲基丙烯酸甲酯骨水泥粉末、万古霉素和配比液（5:0.25:1.6克）。各样品浸渍于磷酸盐缓冲盐水(PBS)中，每天更换浸泡液，每周留取第一天、第三天洗脱液，持续8周。8周后解冻样品，通过高效液相色谱法（评价性HPLC）测定浸泡液中万古霉素浓度。结果：万古霉素从磷酸钙骨水泥/万古霉素复合体中洗脱浓度在第1天最大，然后急剧下降但可以继续有效洗脱至少53天。万古霉素对于MRSA的最小抑制浓度（MIC）的是0.78-3.13微克/毫升,磷酸钙骨水泥万古霉素复合体第53天浸泡液中的的万古霉素仍远大于MIC。万古霉素从聚甲基丙烯酸甲酯骨水泥/万古霉素复合体中洗脱浓度在第1天最大，然后急剧下降但可以继续洗脱39天。然而，洗脱液中万古霉素浓度在第36天基本低于MRSA的MIC，无法达到有效杀菌效果。第1天万古霉素在磷酸钙骨水泥/万古霉素复合体中的洗脱浓度是聚甲基丙烯酸甲酯骨水泥/万古霉素复合体的1.30倍，第1周为1.37倍，第2周为1.96倍，第3周为3.12倍,第4周为3.93倍，第5周为6.30倍。万古霉素从磷酸钙骨水泥/万古霉素复合体和聚甲基丙烯酸甲酯骨水泥/万古霉素复合体可以检测到的释放周期分别为53天，39天。结论：与聚甲基丙烯酸甲酯骨水泥相比，磷酸钙骨水泥释放万古霉素的时间更长、剂量更大，是治疗慢性骨髓炎的理想的药物缓释载体。
[Abstract]:Background: chronic osteomyelitis is a difficult medical problem for orthopedic doctors because of its complex condition, long course of disease, local bone defect and easy recurrence. According to the pathological changes and treatment principles of chronic osteomyelitis, the clinicians made many attempts with the guiding ideology of local debridement, the selection of sensitive antibiotics and the repair of bone defects in the diseased areas. Local use of polymethyl methacrylate (PMMA) cement as a carrier to release high dose antibiotics together with systemic antibiotics is the current standard for the treatment of chronic osteomyelitis. However, PMMA has the disadvantages of heating during cement polymerization and requiring secondary surgical removal. Recently, calcium phosphate cement (CPC) has been used as bone substitute and amplification, and it has no effect on drug activity during polymerization. The time difference of vancomycin (VCM) loaded with calcium phosphate cement (CPC) and (PMMA) loading vancomycin (VCM) (PMMA) has not been clearly studied in China. Objective: to compare the concentration and time of calcium phosphate cement (CPC) loaded VCM and polymethyl methacrylate cement (PMMA) loaded VCM in order to provide experimental basis for clinical application. Methods: the test samples included calcium phosphate cement or polymethyl methacrylate cement powder, vancomycin and mixture solution (5: 0.25: 1.6 g). Each sample was impregnated with phosphate buffer saline (PBS). The solution was changed daily, the first day and the third day of each week were retained. The samples were thawed after 8 weeks. The concentration of vancomycin in soaking solution was determined by high performance liquid chromatography (HPLC). Results: the elution concentration of vancomycin from calcium phosphate cement / vancomycin complex was the highest on the first day and then decreased sharply but could continue to be eluted effectively for at least 53 days. The minimum inhibitory concentration of vancomycin on MRSA was 0.78-3.13 渭 g / ml, and the vancomycin in the solution of calcium phosphate cement vancomycin complex on the 53rd day was still much larger than MIC.. The elution concentration of vancomycin from polymethyl methacrylate bone cement / vancomycin complex was the highest on day 1, then decreased sharply but could be eluted for 39 days. However, the concentration of vancomycin in eluent was lower than that of MIC, with MRSA on the 36th day. On day 1, the elution concentration of vancomycin in calcium phosphate cement / vancomycin complex was 1.30 times as much as that of polymethyl methacrylate bone cement / vancomycin complex, 1.37 times in the first week, 1.96 times in the second week and 3.12 times in the third week. It was 3.93 times in the fourth week and 6.30 times in the fifth week. The release periods of vancomycin from calcium phosphate cement / vancomycin complex and polymethyl methacrylate cement / vancomycin complex were 53 days / 39 days respectively. Conclusion: compared with polymethyl methacrylate cement, calcium phosphate cement can release vancomycin for longer time and larger dosage. It is an ideal drug delivery carrier for the treatment of chronic osteomyelitis.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R681.2

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