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1. 发明申请

WO2005016353A1 TOPICAL OINTMENT FOR VESICATING CHEMICAL WARFARE AGENTS 审中-公开
标题翻译：化学品保护剂代用品的主题
公开(公告)号：WO2005016353A1
公开(公告)日：2005-02-24
申请号：PCT/US2004/000833
申请日：2004-01-14
申请人： U.S. ARMY MEDICAL RESEARCH AND MATERIAL COMMAND DEPARTMENT OF THE ARMY , ARROYO, Carmen, F. , BURMAN, Damon, L.
发明人： ARROYO, Carmen, F. , BURMAN, Damon, L.
IPC分类号： A61K31/593
CPC分类号： A61K31/593 , A61K9/0014 , A61K31/19
摘要： The regulatory effects of the active form of vitamin D, 1-α, 25-dihydroxyvitamin D 3 (1-α, 25(OH) 2 D 3 ) were assessed on the cytokine and chemokine secretion induced by sulfur mustard (HD) on human skin fibroblasts (HSF) and human epidermal keratinocytes (HEK). Stimulation of HSF with HD (10 -4 M for 24 hours at 37° C) resulted in about a 5-fold increase in the secretion of interleukin-6 (IL-6) and over a 10- fold increase for interleukin-8 (IL-8), which was inhibited by 1-α, 25(OH) 2 D 3 , at ≤ 10 -9 M. 1-α, 25(OH) 2 D 3 also suppressed IL-8 secretion by five-fold and IL-6 by four-fold on HD-stimulated HEK at concentrations ≤ 10 -9 M. The effect of 1-α, 25(OH) 2 D 3 was dose-dependent for the suppression of IL-6 and IL-8 induced by HD on HSF/HEK, apparent at nanomolar concentrations. Results indicate that the suppression of these inflammatory mediators by 1-α, 25(OH) 2 D 3 is dependent on the source of the primary cultures, cell densities, and kinetics of pretreatments. In addition, a composition for a topical ointment for wound healing in mammals exposed to vesicating chemical warfare agents is also disclosed. The composition includes a compound or the combination of a 1-α, 25(OH) 2 D 3 and shark liver oil. The steroid hormone 1-α, 25(OH) 2 D 3 (calcitriol), in addition to its crucial role in calcium homeostasis, provides benefits to the immune system by regulating cell proliferation, differentiation and maturation. These benefits are effectuated through the control of protooncogenes and the regulation of cytokine production.
摘要翻译：对维生素D，1-α，25-二羟基维生素D3（1-α，25（OH）2D3）的活性形式的调节作用对由硫芥末（HD）对人皮肤成纤维细胞诱导的细胞因子和趋化因子分泌进行评估 HSF）和人表皮角化细胞（HEK）。用HD（10 -4 M在37℃下刺激24小时）刺激HSF导致白介素-6（IL-6）分泌增加约5倍，白细胞介素-6 8（IL-8），其在1 =α，25（OH）2D3受1-α，25（OH）2D3的抑制，也抑制IL-8分泌5倍和IL-6在HD-刺激的HEK浓度<= 10 -9 M时为4倍。1-α，25（OH）2D3的作用对于抑制IL-6和IL- 8由HD在HSF / HEK上诱导，以纳摩尔浓度表现。结果表明，通过1-α，25（OH）2D3抑制这些炎症介质取决于原代培养的来源，细胞密度和预处理的动力学。此外，还公开了暴露于泡沫化学战剂的哺乳动物中用于伤口愈合的外用软膏组合物。组合物包括化合物或1-α，25（OH）2D3和鲨鱼肝油的组合。类固醇激素1-α，25（OH）2D3（骨化三醇）除了其在钙稳态中的关键作用外，通过调节细胞增殖，分化和成熟为免疫系统提供了益处。这些益处通过控制原癌基因和细胞因子产生的调节来实现。

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