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A Research of Drug Delivery System by Time-Varying Electric Field - Development of high performance electric infiltration anesthesia -

时变电场给药系统的研究 - 高性能电浸润麻醉的研制 -

基本信息

批准号：
08407066
负责人：
UMINO Masahiro
金额：
$ 22.08万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

A Study for the basic mechanism of the high frequency AC iontophoresis (HFIP) has been pursued. First, we examined the efficiency of the by measuring the impedance of the solution in the receptor side of the diffusion cell. Several frequencies and a few voltages of external sinusoidal electric fields were used to evaluate the frequency dependency and the voltage dependency of the HFIP.The permeable efficiency of the saline by HFIP increased with the increase of the external electric voltage up to 〜15 V and leveled off at the voltages larger than 15 V. A physical model was proposed to explain the mechanism of HFIP. The theory of physical model is as follows ; the ion-dipole interactions are broken by the vibrational energy of the ion supplied by the external electric field. The decrease of the effective Stokes radius causes the increase of the diffusion coefficient of the ion.The permeable efficiency of the lidocaine by HFIP showed the maximum value at the frequency 〜300 Hz when the voltage was 30 V. A theoretical model that the rotational energy of the ion supplied by the external electric field break the 'ice burg' of the surrounding water molecules and that the decrease of the effective Stokes radius follows it.It has been cleared that the shape of the external electric field affects the efficiency of the HFIP. A convergent shape electric field transport ions more effectively than the divergent or the parallel electric field.We have developed a method of measuring the concentration of the lidocaine under the rat's skin with the microdialysis probe. This method will give us data of the drug distribution under the skin.The HEIP of the 20 % lidocaine effectively anesthetized the forearm nerve without adverse events. It can be concluded that the HFIP is a new and safe technique for the transdermal drug delivery.

对高频交流离子透入（HFIP）的基本机理进行了研究。首先，我们通过测量扩散池受体侧溶液的阻抗来检验扩散池的效率。采用几个频率和几个电压的外部正弦电场来评估HFIP的频率依赖性和电压依赖性。HFIP对盐水的渗透效率随着外加电压的增加而增加，最高可达~ 15 V，当外加电压大于15 V时，渗透效率趋于平稳。提出了一个物理模型来解释HFIP的机理。物理模型的理论如下：离子-偶极相互作用被外加电场提供的离子的振动能量所打破。有效斯托克斯半径的减小引起离子扩散系数的增大。HFIP对利多卡因的渗透效率在频率~ 300 Hz处电压为30 V时达到最大值。一个理论模型认为，由外电场提供的离子的旋转能量打破了周围水分子的“冰堡”，有效斯托克斯半径随之减小。研究表明，外电场的形状会影响HFIP的效率。收敛型电场比发散型或平行型电场更有效地输运离子。我们开发了一种用微透析探针测量大鼠皮肤下利多卡因浓度的方法。这种方法将给我们提供药物在皮肤下分布的数据。20%利多卡因的HEIP有效麻醉前臂神经，无不良反应。结果表明，HFIP是一种安全的经皮给药新技术。