载利福平、异烟肼、吡嗪酰胺、莫西沙星骨水泥物理性能及洗脱性能的体外研究
An in vitro experimental study on the physical and elution properties of PMMA bone cement loaded with rifampicin, iso-niazid, pyrazinamide and moxifloxacin
摘要目的探讨抗结核药物利福平(rifampicin,RFP)、异烟肼(isoniazid,INH)、吡嗪酰胺(pyrazinamide,PZA)、莫西沙星(moxifloxacin,MFX)分别与Palacos R PMMA骨水泥混合制备用于关节结核人工关节置换术中的载抗结核药物骨水泥(antituberculotic?loaded bone cement,ATLBC)的可行性。方法将不含抗生素的Palacos R PMMA骨水泥分别与RFP、INH、PZA、MFX按40 g∶1 g、40 g∶2 g的比例混合,依据ISO 5833:2002标准制备载药骨水泥标准试件共8组;对照组为未混合抗结核药物的Palacos R PMMA骨水泥,同法制备标准试件。对各组分别进行物理特性(平均面团时间、平均凝固时间、平均最高温度)测定、混合后20 min及硬化后的机械强度(抗压强度、抗弯强度、抗弯模量)测定及不同时间点洗脱液药物浓度测定。结果 RFP(1 g)组、RFP(2 g)组、INH(1 g)组、INH(2 g)组平均面团时间、平均凝固时间均长于对照组,超过了ISO标准的规定范围,平均最高温度较对照组明显降低;INH(1 g)组、INH(2 g)组于混合后14 d硬化,RFP(1 g)组、RFP (2 g)组混合后30 d硬化;且混合后20 min及硬化后的抗压强度、抗弯强度、抗弯模量测定结果均低于ISO标准的规定值。PZA(1 g)组、PZA(2 g)组、MFX(1g )组、MFX(2 g)组及对照组的物理特性、机械强度测定结果均符合ISO标准的规定,且混合后20 min即硬化。RFP(1 g)组、RFP(2 g)组、INH(1 g)组、INH(2 g)组、PZA(1 g)组、PZA(2 g)组、MFX(1 g)组和MFX(2 g)组洗脱液药物浓度分别可维持3 d、7 d、90 d、90 d、45 d、60 d、60 d和60 d。结论 RFP、INH与Palacos R PMMA骨水泥混合后均会阻碍骨水泥的聚合,不适于制备载药骨水泥。PZA、MFX与Palacos R PMMA骨水泥混合后不影响其物理特性,具有良好的机械强度,且有较好的洗脱性能。但因PZA最低抑菌浓度较高,故其抗菌活性维持时间较短;MFX抗菌活性维持时间较长,更适于制备载药骨水泥。
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abstractsObjective To investigate the feasibility of Antituberculotic?loaded bone cement (ATLBC) prepared by mix?ing the anti?TB drugs Rifampicin (RFP), Isoniazid (INH), Pyrazinamid (PZA), Moxifloxacin (MFX) with Palacos R PMMA bone cement in Total Joint Arthroplasty treatment for Joint Tuberculosis. Methods Forty grams of Palacos R bone cement powder without antibiotics was mixed with 1 or 2 grams of RFP, INH, PZA and MFX respectively. According to ISO 5833:2002 stan?dard, 8 groups of ATLBC standard test specimen were prepared as experiment group and Palacos R PMMA bone cement with?out antibiotics was prepared as control group. Physical properties (such as the average dough time, curing time, maximum tem?perature), mechanical strength (such as the compressive strength, the bending resistance strength, the modulus of elasticity) and the concentrations of eluant drug in different time points of ATLBC were detected. Results In RFP (1 g), RFP (2 g), INH (1 g) and INH (2 g) group, the average dough time and curing time were longer than those in control group, which exceeded the standard scope of ISO, while the average maximum temperature was significantly lower than that in control group. The INH ( 1 g) group and INH (2 g) group hardened after mixing for 14 days. The RFP (1 g) group and RFP (2 g) group hardened after mixing for 30 days. Twenty minutes after mixing and hardening, the compressive strength, bending resistance strength and modulus of elastic?ity were significantly lower than the specified values of ISO standard. The physical properties and mechanical strength in PZA ( 1 g) group, PZA (2 g) group, MFX (1 g) group, MFX (2 g) group and control group were in accordance with the specified values of ISO standard, and they hardened after 20 minutes. In RFP (1 g) group, RFP (2 g) group, INH (1 g) group, INH (2 g) group, PZA (1 g) group, PZA (2 g) group, MFX (1 g) group and MFX (2 g) group, the concentration of eluant could maintain for 3 days, 7 days, 90 days, 90 days, 45 days, 60 days, 60 days and 60 days respectively. Conclusion RFP and INH mixing with Palacos R PMMA bone cement can hinder the aggregation of bone cement so they are unsuitable for preparing ATLBC. PZA and MFX mixing with Palacos R PMMA bone cement do not affect the physical properties of bone cement, with excellent mechanical strength and elu?tion properties. Because the minimal inhibitory concentration of PZA is higher and its antimicrobial activity maintains shorter time, while MFX maintains longer time in antimicrobial activity, it's more suitable for the preparation of ATLBC.
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