Studies on Transdermal Therapeutic System using pulse iontophoresis

以裸鼠皮肤为模型，研究了模型药物的体外离子渗透行为。1.在以水杨酸钠作为低分子模型化合物的初步研究中(1988年研究计划(1))，发现药物通量与直流离子导入时的电流密度成正比，与脉冲离子导入时的“开启”时间和电流密度成正比。2.不同方式离子导入后皮肤的阻抗变化和组织学改变表明：(1)阴极电流对皮肤的影响比阳极电流更明显；(2)在相同的有效离子导入时间下，脉冲电流对皮肤的损伤比直流电流轻。因此，使用脉冲电流可以对皮肤施加更高的电流密度和更长的净离子导入周期。对超氧化物歧化酶作为模型多肽药物的离子电泳法研究表明，由于其高分子量的性质，极少量的超氧化物歧化酶通过离体皮转运(的研究计划(1))。4.提出了乳酸十六酯和油酸对消炎痛大鼠经皮透皮吸收的促进作用(1988年和1989年研究计划(4))。然而，要将这些增强剂应用到离子导入体系中，还必须解决一些问题，如水的溶解性等，开发一种离子导入装置并进行更广泛的体内研究是必要的。

Iontophoretic penetration of model drugs was investigated in vitro using the excised nude mouse skin. 1. In the preliminary study using sodium salicylate as a low-molecular model compound (research plan (1) for 1988), it was found that the flux of drug was proportional to the current density at direct current iontophoresis and to both the "on" time and current density at pulse iontophoresis. 2. The impedance change and histological alteration of the excised skin after the application of various modes of iontophoresis revealed that (1) the cathodic current had more marked effects on the skin than the anodic current, (2) the pulse current induced a milder tissue damage than the direct current when compared at the same effective applied time of iontophoresis. Therefore, a higher current density and a longer net period of iontophoresis could be applied to the skin with the use of pulse current.3. The iontophoretic study on SOD as a model polypeptide-drug, showed that a very small amount of SOD was transported through the excised skin owing to its high-molecular-weight properties (research plan (1) for 1989). 4. The enhancing effect of cetyl lactate and oleic acid on the percutaneous absorption of indomethacin through the abdominal skin of rats was suggested (research plan (4) for 1988 and 1989). However, some problems such as water solubility must be solved to apply these enhancers to the iontophoretic system.The development of a iontophoretic device and more extensive investigations in vivo are necessary.