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Iontophoretic application of prostaglandin E1 for the treatment of peripheral arterial occlusive disease

前列腺素E1离子导入治疗外周动脉闭塞性疾病

基本信息

批准号：
09671222
负责人：
MATSUSHITA Masahiro
金额：
$ 2.11万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

项目摘要

Prostaglandin E1 (PGE1) administered intra-arterially or intravenously has been used clinically in the treatment of peripheral arterial occlusive disease (PAOD). However, intraarterial infusion of PGE1 into an artery is invasive. Intravenous administration of PGE1 is less efficacious and may cause a steal phenomenon. We used iontophoresis to allow high concentrations of PGE1 to be delivered directly to the ischemic foot. Our in vitro study showed that PGE1 permeated through hairless mouse skin iontophoretically, but not by passive transport. Nineteen patients with Arteriosclerosis Obliterans were given PGE1 (20mg) iontophoretically on the dorsum of the foot. The increase rate in cutaneous blood flow as measured by Laser Doppler Flux (LDF) level was significantly higher in the PGE1 than in the control saline. The percent increase in LDF levels with PGE1 was similar in the patients with intermittent claudication and that in critical leg ischemia patients. The percent increase in LDF level was significantly higher with iontophoresis than with intravenous drip infusion of PGE1. Iontophoretic application of the PGE1 was used for the purpose of the treatment of an ischemic foot ulcer in 9 patients. Of those, 4 patients were treated successfully. The percent increase in LDF level was significantly higher in 4 patients treated successfully than in those with failed treatment. This preliminary study addressed the transdermal delivery of PGE1 and the microcirculatory effect of iontophoretically applied PGE1. Iontophoretically delivered PGE1 was beneficial in patients with ischemic ulcer if this treatment could increase blood flow of the skin close to the ulcer.

动脉内或静脉内给药的前列腺素 E1 (PGE1) 已在临床上用于治疗外周动脉闭塞性疾病 (PAOD)。然而，将 PGE1 动脉内输注到动脉中是侵入性的。静脉注射PGE1效果较差，并可能导致偷窃现象。我们使用离子电渗疗法将高浓度的 PGE1 直接输送到缺血足部。我们的体外研究表明，PGE1 通过离子电渗疗法渗透过无毛小鼠皮肤，但不是通过被动转运。 19 名患有动脉硬化闭塞症的患者在足背上接受了 PGE1（20 毫克）离子电渗疗法。通过激光多普勒通量 (LDF) 水平测量，PGE1 中的皮肤血流量增加率显着高于对照盐水。间歇性跛行患者和严重腿部缺血患者的 LDF 水平与 PGE1 的增加百分比相似。离子电渗疗法的 LDF 水平增加百分比显着高于静脉滴注 PGE1。 PGE1 的离子电渗疗法用于治疗 9 名患者的缺血性足部溃疡。其中，4名患者得到成功救治。 4 名治疗成功的患者的 LDF 水平增加百分比显着高于治疗失败的患者。这项初步研究探讨了 PGE1 的透皮递送以及离子电渗疗法应用的 PGE1 的微循环效应。如果离子电渗疗法能够增加溃疡附近皮肤的血流量，那么这种治疗方法对缺血性溃疡患者是有益的。