Novel Inhibitors of Chemical Absorption Through Skin

皮肤化学吸收的新型抑制剂

• 批准号: 6549160
• 负责人: JOSEPH A DUNN
• 金额: $ 9.95万
• 依托单位: OMNIPHARM RESEARCH INTERNATIONAL INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6549160
• 关键词: chemical structure function; clinical research; drug adverse effect; drug design /synthesis /production; human tissue; inhibitor /antagonist; keratinocyte; laboratory rabbit; laboratory rat; membrane permeability; skin absorption; skin pharmacology; topical drug application; toxicology; transdermal drug delivery

DESCRIPTION (provided by applicant): The goal of this revised Phase 1 proposal remains to identify and initiate the pharmaceutical development of a topical formulation ingredient capable of reducing the risk associated with dermal and systemic exposure to hazardous materials (i.e., a permeation retarder). The strategy is to select a lead chemical entity from several candidate molecules designed to interact with the stratum comeum so that it becomes less permeable to toxic agents. The selection of an effective skin permeation retarder will be based upon its ability to reduce the skin absorption of a variety of hazardous materials, be substantive to skin such that it will be active for prolonged periods of time, and show essentially no dermal toxicity. In Phase I of this project we intend to synthesize and evaluate in vitro the permeation retardant efficacy of several potential retarder candidates, perform primary dermal and acute oral toxicity analysis in animals of a lead and back-up candidate, and perform formulation studies that will generate prototype products. In Phase II we will seek to scale-up the synthesis of the lead compound, optimize potential formulations, determine long-term chemical, microbiological and physical stability, and complete safety and efficacy studies as required by the FDA. PROPOSED COMMERCIAL APPLICATION: The $20 B personal care product market covers a collection of diverse products, most of which involve contact with the skin. Many of the ingredients of such products are irritants or sensitizers and some may be systemically toxic. A general ingredient that will reduce the skin absorption of such materials should find widespread use in this market. In addition, an effective skin barrier formulation might also find use in pharmaceutical, occupational, military and household environments.

描述（由申请人提供）：本修订后的第一阶段提案的目标仍然是确定并启动局部制剂成分的药物开发，该成分能够降低与皮肤和全身暴露于有害物质（即渗透阻滞剂）相关的风险。该策略是从设计用于与角质层相互作用的几个候选分子中选择一种主要化学实体，从而使其对有毒物质的渗透性降低。有效的皮肤渗透阻滞剂的选择将基于其减少皮肤对各种有害物质的吸收的能力、对皮肤的亲和性使得其将具有较长时间的活性、并且基本上不表现出皮肤毒性。在该项目的第一阶段，我们打算在体外合成和评估几种潜在的缓凝剂候选物的渗透阻滞功效，对主要候选物和备用候选物的动物进行主要皮肤和急性口服毒性分析，并进行配方研究以产生原型产品。在第二阶段，我们将寻求扩大先导化合物的合成规模，优化潜在配方，确定长期化学、微生物和物理稳定性，并按照 FDA 的要求完成安全性和有效性研究。 拟议的商业应用：20 B 美元的个人护理产品市场涵盖了一系列不同的产品，其中大多数涉及与皮肤接触。此类产品的许多成分都是刺激物或致敏剂，有些可能具有全身毒性。 会减少皮肤对此类材料吸收的通用成分应该在这个市场上得到广泛使用。 此外，有效的皮肤屏障配方还可用于制药、职业、军事和家庭环境。