Topical Cyclosporin A Treatment for Psoriasis

局部环孢素 A 治疗牛皮癣

• 批准号: 6833055
• 负责人: John Michael Newsam
• 金额: $ 9.99万
• 依托单位: FQUBED, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6833055
• 关键词: combinatorial chemistry; cyclosporines; drug delivery systems; drug design /synthesis /production; high throughput technology; hydropathy; psoriasis; skin absorption; surfactant; topical drug application; transdermal drug delivery

DESCRIPTION (provided by applicant): Orally delivered cyclosporin A (CsA) is an effective treatment that is used in patients with severe psoriasis. The availability of a topical CsA treatment could provide significant benefit to psoriasis patients. An effective topical CsA formulation could mitigate the side effects of this powerful drug, which include nephrotoxicity and hypertension thereby increasing the breadth of the psoriasis patient population base who might benefit from CsA to include those with mild or moderate symptoms. Past attempts to develop a topical CsA treatment have been largely ineffective. The skin is an excellent barrier for most molecules with a molecular weight of more than 500 Da and has been argued that the relatively high molecular weight of CsA (1,200 Da) hinders the transport of the drug across the stratum corneum. Recently, Mitragotri and coworkers have developed novel combinations of penetration enhancers (SCOPE formulations) that are able to greatly improve the permeability of the stratum corneum. SCOPE compositions have been shown to be effective in delivering molecules with molecular weight of up to 5,000 Da, with minimal levels of skin irritation. We propose here to build on these discoveries to develop topical formulations that are effective in treatment of psoriasis using CsA. In Phase I of the proposal a novel high throughput experimentation system will be used to identify substantially non-irritating formulations that are capable of producing a fifty-fold improvement in the amount of CsA that can be delivered to the skin compared to a standard formulation. In Phase II of the project the leading formulations developed in Phase I will be subjected to animal testing and a small-scale human trial. A topical formulation capable of delivering CsA might also find use as a basis for administering this drug for other indications such as, for example, atopic dermatitis.

描述（由申请人提供）： 口服递送的环孢菌素A（CSA）是一种有效的治疗方法，用于严重牛皮癣患者。局部CSA治疗的可用性可以为牛皮癣患者带来重大好处。有效的局部CSA配方可以减轻这种功能强大的药物的副作用，其中包括肾毒性和高血压，从而增加牛皮癣患者人群的广度，这些牛皮癣患者群体可能会从CSA中受益，以包括患有轻度或中度症状的牛皮癣。过去开发局部CSA治疗的尝试在很大程度上是无效的。皮肤是大多数分子量超过500 Da的分子的绝佳障碍，并被认为CSA的分子量相对较高，CSA（1,200 DA）阻碍了该药物在整个角质层上的转运。最近，Mitragotri及其同事开发了渗透增强剂（范围配方）的新型组合，这些组合能够大大提高角质层的渗透性。范围组成已被证明可以有效地递送分子量高达5,000 dA的分子，皮肤刺激水平最小。我们在这里建议以这些发现为基础，以开发有效使用CSA治疗牛皮癣的局部配方。在该提案的I期中，新型的高通量实验系统将用于确定基本的非灌溉配方，该制剂能够在与标准配方相比，能够在CSA量中产生五十倍的CSA量。在该项目的第二阶段中，第一阶段开发的主要制剂将进行动物测试和小规模的人类试验。能够输送CSA的局部配方也可能会发现用作用于其他适应症的药物的基础，例如特应性皮炎。