高分子微泡超声对比剂制备条件的优化  

Optimization research on preparation conditions of polymer-shelled microbubble contrast agents

作　　者：黄宏杰[1] 林鹏[1] 黄嵘森 林艺凯 苏婕[1] 陈琬萍 林礼务[2] 薛恩生[2] 陈志奎[2] 

机构地区：[1]福建医科大学医学技术与工程学院医学影像系,福建省福州市350001 [2]福建医科大学附属协和医院超声科,福建省福州市350001

出　　处：《中国组织工程研究》2014年第30期4857-4862,共6页Chinese Journal of Tissue Engineering Research

基　　金：全国大学生创新创业训练计划项目(201310392022)~~

摘　　要：背景:前期实验采用左旋聚乳酸-甲基端聚乙二醇包裹液态氟碳全氟戊烷成功制备了高分子微泡超声对比剂,其在体内外低机械指数二次谐波超声造影模式下显影良好。目的:优化高分子微泡超声对比剂的制备条件,以制备产量大、粒径适宜且分布均匀的微泡。方法:采用单乳化法制备包裹液态氟碳全氟戊烷的高分子微泡超声对比剂,以微泡产量与粒径大小及分布为评价指标,分别对高分子聚合物质量与液态氟碳体积比(4/1、2/1、1/1、1/2)、电动内切匀浆的转速(18 000,26 000,35 000 r/min)、匀浆时间(15,30,60,120 s)3个制备条件进行优化。以优化条件制备的高分子微泡超声对比剂进行新西兰大白兔肾脏超声造影,TCA软件分析造影的始增时间、达峰时间、峰值降半时间及峰值强度等参数。结果与结论:高分子微泡超声对比剂的优化条件为:高分子聚合物质量与液态氟碳体积比为2/1,匀浆转速为26 000 r/min,匀浆时间为60 s,此时微泡产量为(1.8±0.4)×109/mL,粒径(3.7±1.3)μm且分布较均匀。新西兰大白兔肾脏造影的始增时间为(3.1±0.6)s,达峰时间为(2.9±0.5)s,峰值降半时间为(4.0±0.7)s,峰值强度为(4.7±1.1)×10-5 AU,说明高分子微泡体内造影效果好。BACKGROUND： In previous experiments, a polymer-shelled microbubble contrast agent was successfully prepared using L-polylactic acid-polyethylene glycol methyl-covered liquid fluorocarbon perfluoropentane, which developed well in vivo and in vitro under a second harmonic contrast-enhanced ultrasound with a low mechanical index OBJECTIVE： To optimize the con~：litions for preparing polymer-shelled microbubble contrast agents with high yield and suitable size. METHODS： The polymer-shelled microbubble contrast agent containing perfluoropentane was prepared by single emulsion method. Three preparation conditions, including polymer mass/perfluoropentane volume ratio （4/1, 2/1, 1/1, 1/2）, hemogenate speed （18 000, 26 000, 35 000 r/min） and time （15, 30, 60, 120 seconds）, were optimized, and the microbubble yield and size were set as judge standard. The contrast-enhanced ultrasonography of rabbit kidney was performed using the optimized microbubbles, and the arrival time, time to peak, half time of descending and peak intensity were analyzed by TCA software. RESULTS AND CONCLUSION： The preparation conditions were optimized as a polymer mass/perfluoropentane volume ratio of 2/1, homogenate speed of 26 000 r/min and homogenate time of 60 seconds, which presented ahigh microbubble yield of （1.8±0.4）×109/mL and mean size of （3.7±1.3） pm with uniform distribution. The arrival time, time to peak, half time of descending and peak intensity were detected as （3.1±0.6） seconds, （2.9±0.5） seconds, （4.0±0.7） seconds and （4.7±1.1）×10 s AU, respectively. The polymeric microbubbles prepared by optimized conditions were of high yield, with suitable size and good contrast-enhanced effect in vivo.

关 键 词：生物材料 材料相容性 高分子对比剂 嵌段共聚物 全氟戊烷 单乳化法 低机械指数二次谐波超声造影 

分 类 号：R318[医药卫生—生物医学工程]