Kadar Tamar, Fishbine Eliezer, Meshulam Jacob, Sahar Rita, Amir Adina, Barness Izhak
Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel.
Isr Med Assoc J. 2003 Oct;5(10):717-9.
Sulfur mustard and VX are potent chemical warfare agents that penetrate rapidly through the skin, causing severe prolonged injuries and sometimes death.
To develop a topically applied pretreatment that will act as a barrier and prevent the absorption of these agents through the skin, reducing morbidity and saving life.
Several formulations were developed and tested in preclinical animal studies in pigs. The protecting cream was applied as a single application (0.5-1 ml/100 cm2) prior to exposure (10 minutes to 12 hours) to sulfur mustard or VX. Assessment of sulfur mustard-induced skin damage was based on clinical and histologic evaluations. When tested against VX, clinical signs and blood cholinesterase activity were monitored. At the final stage of development, safety studies were conducted in animals and in human volunteers.
The formulation that gave the best results, coded IB1 (under patent application), provided significant protection against a 1 hour exposure to sulfur mustard (droplets or vapor). All the pigs pretreated with IB1 cream survived a 1-4 hour challenge of 2xLD50 VX and did not exhibit any overt clinical signs. Protection was exhibited even when the cream was applied 12 hours (single application) prior to exposure. IB1 was found to be non-irritating in animals and humans. No adverse effects were found in a Phase I clinical study in young healthy volunteers when the cream was applied to around 20% of the skin surface (results presented elsewhere).
IB1 cream has been shown to be a safe and effective topical skin protectant against the chemical warfare agents sulfur mustard and VX.
芥子气和VX是强效化学战剂，可迅速穿透皮肤，造成严重的长期损伤，有时甚至导致死亡。
研发一种局部应用的预处理方法，作为屏障以防止这些战剂经皮肤吸收，从而降低发病率并挽救生命。
研发了几种制剂并在猪的临床前动物研究中进行测试。在暴露于芥子气或VX之前（10分钟至12小时），以单次涂抹（0.5 - 1毫升/100平方厘米）的方式涂抹防护乳膏。基于临床和组织学评估对芥子气所致皮肤损伤进行评估。在针对VX进行测试时，监测临床体征和血液胆碱酯酶活性。在研发的最后阶段，在动物和人类志愿者中进行了安全性研究。
效果最佳的制剂，编码为IB1（正在申请专利），对1小时的芥子气暴露（液滴或蒸气）提供了显著保护。所有用IB1乳膏预处理的猪在2倍半数致死剂量VX的1 - 4小时攻击中存活下来，且未表现出任何明显的临床体征。即使在暴露前12小时（单次涂抹）涂抹乳膏，仍显示出保护作用。发现IB1在动物和人类中均无刺激性。在年轻健康志愿者的I期临床研究中，当乳膏涂抹于约20%的皮肤表面时，未发现不良反应（结果在其他地方呈现）。
已证明IB1乳膏是一种安全有效的局部皮肤防护剂，可抵御化学战剂芥子气和VX。
