DEVELOPMENT OF DISINTEGRATION AND CONTROL TECHNIQUE OF MICROCAPSULES INCLUDING A GAS BUBBLE FOR DRUG DELIVERY SYSTEMS USING UNDERWATER SHOCK WAVE

最近冲击波和冲击波技术。应用于医疗和生物技术行业，特别是体外冲击波碎石术（ESWL），骨科骨重建，药物基因治疗。激波是一种传播速度大于声速的大压力变化波，其特点是(1)上升频率大的单波、不连续波，(2)持续时间约为微秒级，(3)单位时间内能量传递大。利用这些特点，需要新的医学和工业技术，但细胞分解的基本机制尚未阐明。本研究的目的是研究这一机制，并将冲击波技术应用于生物加工工业和医学领域。本课程组开展了利用冲击波和气泡进行细胞崩解的研究，并利用它们开发了新的生物过程和给药系统。本课题与德国埃尔兰根大学流体力学研究所（LSTM）合作，主要研究三个课题：(1)紊流剪切应力作用下的胶囊崩解（Reynolds剪应力）；(2)冲击波作用下的胶囊崩解及胞体变形过程数学模型的建立；(3)利用冲击波崩解含气泡的微胶囊，应用于药物输送系统（DDS），本项目的研究结果如下：(1)湍流剪切流中细胞整合的剪应力阈值为1200 ~ 1400 Pa，该结果也适用于人造器官如血泵和其他医疗流动装置的开发。(2)修正了球壳-水相互作用的数学模型，研究了不同参数（膜厚度和杨氏模量）下超声和激波对单胞和双胞在水中的变形和损伤。(3)采用任意拉格朗日-欧拉（ALE）计算方法分析了含气泡的胶囊在超声和激波作用下的变形过程，发现内部气泡和微射流的不对称性对微胶囊的损伤有较大影响。研究结果表明，今后应利用冲击波控制微胶囊的崩解速率。少

Recently shock waves and shock wave technology are. applied to medical and biotechnological industries, especially extracorporeal shock wave lithotripsy (ESWL), bone reconstruction for orthpaedic, gene therapy with drug. Shock wave is large pressure change wave whose propagating velocity is larger than sound speed, and its features are (1)single and discontinues wave with large rising frequency, (2)duration time is about micro second order, (3) large energy transfer per unit time. Using these features, new technology and technique for medicine and industry are needed, but the fundamental mechanism for cell disintegration has not been, elucidated yeti In this study, our aim is to investigate this mechanism and apply the shock wave technology to disintegrate cell in the bioprocess industry and medical field.In our research group, the study about the cell disintegration using shock wave and a bubble, and also the new bioprocess and drug delivery systems (DDS) using these have being develo … More ped. In this research project, with cooperation of LSTM (Institute of Fluid Mechanics in German) in the University of Erlangen, Germany, which has been in pride of flow measurements and analysis, the following three topics are investigated, (1) Capsule disintegration by turbulent shear stress (Reynolds shear stress), (2)Capsule disintegration and establishment of mathematical cell deformation process model using shock wave, (3)Disintegration of microcapsules including a bubble using shock-wave for applying Drug Delivery Systems (DDS) And the results for these in this projects are(1)The threshold of shear stress for cell integration in turbulent shear flow is from 1200 to 1400 Pa, and this result are also applicable to the development of artificial organs, for instance blood pumps, and other medical flow device.(2)Modifying the mathematical model of spherical shell -water interactions, deformation and damage of a single and two cells in water by ultrasonic and shock wave with changing parameter (thickness of membrane and Young modulus) are investigated.(3)Deformation process of a capsule including, a bubble by ultrasonic and shock wave is analyzed using arbitrary Lagrangian-Eulerian (ALE) computational method, and it is found that asymmetry of internal bubble and micro jet have largeeffects on he damage of microcapsules.Using these results, the microcapsule disintegration rate should be controlled by shock wave in future. Less