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

对高频交流离子导入(HFIP)的基本机理进行了研究。首先，我们通过测量扩散池接收侧溶液的阻抗来检验该方法的效率。研究了几种频率和几个电压的外加正弦电场对HFIP的频率依赖性和电压依赖性的影响。HFIP对盐水的渗透效率随着外加电压的增加而增加，当外加电压大于15V时，渗透效率趋于平稳，并建立了物理模型来解释HFIP的机理。物理模型的原理如下：离子与偶极的相互作用是由外加电场提供的离子的振动能打破的。当电压为30V时，利多卡因对HFIP的渗透效率在~300 Hz处出现最大值。理论模型表明，外加电场使离子的旋转能打破周围水分子的‘冰堡’，有效斯托克斯半径随之减小，表明外电场形状对HFIP的渗透效率有影响。聚合型电场比发散电场或平行电场更有效地传输离子。我们发展了一种用微渗析探头测量大鼠皮肤下利多卡因浓度的方法。这种方法可以给我们提供皮肤下药物分布的数据。20%利多卡因的头针有效地麻醉了前臂神经，没有不良反应。说明HFIP是一种新的、安全的经皮给药技术。

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.