Studies on Transdermal Therapeutic System using pulse iontophoresis

采用离体裸鼠皮肤研究了模型药物的离子电渗渗透。1.在使用水杨酸钠作为低分子模型化合物的初步研究（1988年的研究计划（1））中，发现药物的通量与直流电离子电渗疗法的电流密度成正比，并且与脉冲离子电渗疗法的“接通”时间和电流密度成正比。2.应用不同方式的离子导入后，离体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，使用脉冲电流可以将更高的电流密度和更长的净时间施加到皮肤上。对作为模型多肽-药物的SOD的离子电渗研究表明，由于其高分子量特性，极少量的SOD可通过离体皮肤转运（1989年研究计划（1））。4.有人提出，乳酸鲸蜡酯和油酸对吲哚美辛通过大鼠腹部皮肤的经皮吸收具有增强作用（1988年和1989年研究计划（4））。然而，这些离子导入促进剂的水溶性等问题尚待解决，离子导入装置的研制和更广泛的体内研究也是必要的。

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.