美罗培南骨水泥体外生物力学及洗脱特性研究

目的研究不同含量的美罗培南骨水泥的体外生物力学特性和药物洗脱特性。 方法40 g骨水泥(Palacos LV，40 g聚合物粉剂+20 ml单体液剂)中分别加入2、4、6 g注射用美罗培南和2、4 g注射用盐酸万古霉素复合，制备成A2、A4、A6、B2、B4和不含抗菌药物的对照组共6组样品。对6组样品分别进行能承受的最大压力和剪切力载荷测试，并计算耐压强度、压缩模量。采用高效液相色谱法(HPLC)对美罗培南标准品溶液和美罗培南骨水泥洗脱液进行检测，绘制美罗培南色谱图及标准线性回归方程；检测A4组美罗培南骨水泥在37 ℃恒温条件下浸渍24、48、72 h和6、12、24 d后洗脱液药物浓度，并绘制时间-药物浓度曲线。采用方差分析对样品最大压力载荷、最大剪切力载荷、耐压强度和压缩模量进行比较；采用线性相关与回归分析获得标准线性回归方程。 结果和对照组比较，A2、A6组样品能承受的最大压力载荷和耐压强度相似(P> 0.05)；A4组能承受的最大压力载荷和耐压强度高于对照组(t ＝4.41、4.41，均为P< 0.01)；B2、B4组能承受的最大压力载荷(t ＝9.01、9.01，均为P <0.01)和耐压强度低于对照组(t ＝12.26、12.26，均为P <0.01)；且B4组低于B2组，差异均有统计学意义(t ＝4.01、4.01，均为P <0.01)。A2、A4、A6、对照组样品压缩模量和能承受的最大剪切载荷组间比较，差异无统计学意义(P > 0.05)。B2、B4组压缩模量低于对照组(t＝4.85、8.15，均为P<0.01)，且B4组低于B2组，差异有统计学意义(t＝4.73，P <0.05)。B2、B4组能承受的最大剪切载荷相似(P> 0.05)，但都低于对照组(t＝5.84、5.05，均为P< 0.01)。美罗培南标准品溶液的标准线性回归方程(y ＝15.0265x＋13.5218，R＝1.00)。A4组样品，在37 ℃恒温条件下浸渍24、48、72 h和6、12、24 d后，洗脱液中的美罗培南药物浓度分别为60.05、9.99、4.3、4.05、1.96、0.62 μg/ml。 结论40 g Palacos LV骨水泥中加入最多6 g美罗培南时，不降低骨水泥的力学特性，同时优于相同含量万古霉素骨水泥的力学特性。10%含量的美罗培南骨水泥在37 ℃恒温条件下能持续释放美罗培南达24 d。

In vitro biomechanical effects and elution of meropenem-loaded bone cement

Objective To summarize the biomechanical effects and elution of meropenem-loaded bone cement with the different contents.Methods Forty grams of Palacos LV bone cement was respectively added two,four,six grams meropenem,or two and four grams vancomycin or no antibiotic and prepared into a total of six groups cylindrical samples of A2,A4,A6,B2,B4 and control group(antibiotic-free).The maximum compression and shear tests were performed on each group of samples,and the compressive strength and compressive modulus were calculated.The standard curve of meropenem was draw and the regression equation was calculated.At a constant temperature of 37℃,meropenem-loaded bone cement cylinders(A4)were serially immersed in saline solution.The eluent was collected at predetermined time points of 24,48,72 h and six,12,24 d.The drug concentration of eluent was measured by high performance liquid chromatography and the elution kinetics was studied.The analysis of variance(ANOVA)method was used to compare the overall difference of the maximum compression loads,maximum shear loads,compressive strength and compressive modulus between groups.Linear correlation and regression analysis were used to obtain the standard regression equation of meropenem.Results Six groups of samples,A2,A4,A6,B2,B4 and the control group,were successfully made.The maximum compression loads and compressive strengths of group A2,A6 and the control group were similar(P>0.05).The maximum compression load and compressive strength of group A4 were higher than those of control group(t=4.41,4.41,both P<0.01).The parameters of group B2 and B4 were lower than those of the control group(maximum compression load:t=9.01,9.01,compressive strength:t=12.26,12.26,all P<0.05),and those of B4 were lower than those of group B2(t=4.01,4.01,both P<0.05).There were no significant differences in compressive modulus and maximum shear loads between groups A2,A4,A6 and the control group(P>0.05).The compressive modulus of group B2 and B4 were lower than that of control group(t=4.85,8.15,both P<0.05),and that of B4 was lower than that of group B2(t=4.73,P<0.05).The maximum shear loads of B2 and B4 groups were similar,but lower than that of control group(t=5.84,5.05,both P<0.05).The regression equation of meropenem was(y=15.0265x+13.5218,R=1.00).At the time points of 24,48,72 h and six,12,24 d,the drug concentration of eluent were 60.05,9.99,4.3,4.05,1.96μg/ml and 0.62μg/ml respectively.Conclusions When 40 g Palacos LV bone cement is added no more than 6 g meropenem,the biomechanical effects will not be reduced,and they are superior to vancomycin-loaded bone cement with the same contents.At a constant temperature of 37℃,meropenem can be released from bone cement for up to 24 d.