负载利福平骨水泥的制备及体外释放实验研究  

Experimental Study on Preparation and in vitroRelease of Rifampicin-loaded Bone Cement

作　　者：余涌杰[1] 赖震[1] 费骏[1] 胡胜平[1] YU Yongjie;LAI Zhen;FEI Jun;HU Shengping(Department of Orthopedics,Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine,Hangzhou,Zhejiang province,310003,China)

机构地区：[1]浙江省中西医结合医院骨科

出　　处：《浙江中西医结合杂志》2019年第11期894-896,902,共4页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

基　　金：杭州市科技发展计划项目(No.20150733Q41)

摘　　要：目的研究负载利福平骨水泥制备及体外药物释放浓度行为。方法将利福平胶囊按0.75、1.5、2.25g的剂量分别与40g骨水泥在无菌条件下真空搅拌,并加入骨水泥单体15mL,制成直径6mm、厚度3mm的矮圆柱体实验样品,研究分为三组:实验1组,负载0.75g利福平骨水泥;实验2组,负载1.5g利福平骨水泥;实验3组,负载2.25g利福平骨水泥,每组制备6个。测定三组骨水泥的面团时间和凝固时间。将负载不同剂量的利福平骨水泥和空白样骨水泥浸泡于50mL生理盐水中,分别于第3、6、9、12、15天采用高效液相色谱法检测分析不同剂量负载利福平的骨水泥的药物释放浓度、释放持续时间。结果(1)实验1、2、3组负载利福平骨水泥面团时间分别为(6.87±0.59)min、(7.05±0.41)min、(7.38±0.91)min,凝固时间分别为(18.23±0.81)min、(20.47±0.72)min、(21.61±0.53)min;负载不同剂量的利福平后,骨水泥的面团时间和凝固时间均大于对照组,利福平剂量越大,面团时间和凝固时间越长,各实验组间差异有统计学意义(P<0.05);(2)在生理盐水中浸泡后,骨水泥基体中的利福平会逐渐释放,前3天药物释放速率比较平缓,第3天时检测实验1、2、3组释放情况分别为(1.02±0.61)μg/mL、(1.20±1.09)μg/mL、(1.53±1.14)μg/mL,三组间差异有统计学意义(P<0.05);3天后利福平释放开始逐渐加快,在第6天时检测分别为(1.06±0.67)μg/mL、(1.63±1.28)μg/mL、(2.14±1.42)μg/mL,三组间差异有统计学意义(P<0.05);达到释放高峰后释放减慢,到第9天时检测各组释放情况分别为(0.54±0.04)μg/mL、(0.61±0.16)μg/mL、(0.75±0.23)μg/mL,三组间差异有统计学意义(P<0.05),药物释放状态达到平稳缓释效果,在第12天时检测各组释放情况分别为(0.84±0.13)μg/mL、(0.87±0.19)μg/mL、(0.90±0.26)μg/mL,三组间差异无统计学意义(P>0.05)。这种平稳状态并持续释放到实验结束,第15天时检测各组释放情况分别为(0.79Objective To investigate the preparation of rifampicin-loaded bone cement and drug release behavior in vitro.Methods Doses of 0.75,1.5 and 2.25g rifampicin were mixed with 40g bone cement respectively under the condition of vacuum stirring,and the bone cement monomer 15mL was added to make the low cylinder experimental sample with 6mm diameter and 3mm thickness size.The three groups were divided,i.e.,experiment 1 group with loading 0.75g,experiment 2 group with loading 1.5g,and experiment 3 group with loading 2.25g rifampicin bone cement,respectively.Six samples were prepared in each group.The dough time and setting time of bone cement were tested.Different groups of rifampicin-loaded bone cement and blank bone cement were immersed into 50 mL physiological saline for 3,6,9,12 and 15 days,respectively.The drug release concentration and duration of rifampicin-loaded bone cement were determined and analyzed by high performance liquid chromatography.Results(1)The average dough time of the three groups with rifampicin-loaded bone cement was(6.87±0.59),(7.05±0.41)and(7.38±0.91)min,and the average setting time was(18.23±0.81),(20.47±0.72)and(21.61±0.53)min,respectively.After loading different doses of rifampicin,the dough time and setting time of the bone cement were longer than those of the control group,respectively.The higher the dose of rifampicin,the longer the dough time and setting time,the difference was significant(P<0.05);(2)After soaking in normal saline,rifampicin in bone cement matrix released gradually,and the drug release rate was relatively slow in the first three days.On the 3rd day,the release of rifampicin in each group was detected as(1.02±0.61),(1.20±1.09)and(1.53±1.14)μg/mL(P<0.05).Three days later,rifampicin release began to accelerate gradually,and on the 6th day,the release rate of rifampicin was detected as(1.06±0.67),(1.63±1.28)and(2.14±1.42)μg/mL.The release slowed down after reaching the release peak,and at the 9th day,the release rates of each group were(0.54±0.04),(0.61±0.1

关 键 词：利福平 骨水泥 骨结核 缓释 

分 类 号：R52[医药卫生—内科学]