GI safety and therapeutics of oil-based PC-NSAIDs

油基 PC-NSAID 的胃肠道安全性和治疗

• 批准号: 6587060
• 负责人: LENARD M LICHTENBERGER
• 金额: $ 9.9万
• 依托单位: PLX OPCO, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2003-12-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6587060
• 关键词: aspirin; chemical stability; drug adverse effect; drug screening /evaluation; gastrointestinal drug absorption; gastrointestinal pharmacology; ibuprofen; laboratory rat; membrane permeability; nonsteroidal antiinflammatory agent; pharmacokinetics; phosphatidylcholines; prostaglandin endoperoxide synthase; soybeans; ulcer; vegetable oils

DESCRIPTION (provided by applicant): The major objective of this Phase I STTR grant is to evaluate the GI safety, therapeutic activity and stability of a new class of non-steroidal anti-inflammatory drugs (NSAIDs) that are formulated with a soy bean oil that is enriched in phosphatidylcholine (PC). This represents a second generation of PC-NSAIDs, developed by the PI and associates, that would have additional benefits with regards to cost and stability of the drug. The specific aims of this application are focused on confirming preliminary data that the oil-based PC-NSAIDs (and specifically PC-aspirin and PC-ibuprofen) possess low GI toxicity and enhanced therapeutic activity employing rodent models of acute and chronic NSAID-induced ulcer disease, and joint inflammation/pain. We also propose a series of in vivo and in vitro studies to define the molecular basis of the enhanced therapeutics of the PC-NSAIDs, evaluating the drugs' bioavailability, membrane permeability and cyclooxygenase (COX) inhibitory activity. In the last specific aim, we will evaluate the stability of PC-aspirin and PC-ibuprofen in the presence and absence of fluidizers and anti-oxidants in hard capsules employing an encapsulation technique that would limit the NSAIDs' exposure to water, which is particularly critical for aspirin. The above studies will provide us with important information required for the initiation of clinical trials and commercialization of PC-NSAIDs.

描述（由申请人提供）：第一阶段 STTR 资助的主要目标是评估用大豆油配制的新型非甾体抗炎药 (NSAID) 的胃肠道安全性、治疗活性和稳定性富含磷脂酰胆碱（PC）。这代表了由 PI 及其同事开发的第二代 PC-NSAID，它将在药物的成本和稳定性方面具有额外的优势。本申请的具体目的在于确认初步数据，即油基 PC-NSAID（特别是 PC-阿司匹林和 PC-布洛芬）具有较低的胃肠道毒性，并且采用啮齿动物模型对急性和慢性 NSAID 诱发的溃疡具有增强的治疗活性疾病和关节炎症/疼痛。我们还提出了一系列体内和体外研究，以确定 PC-NSAID 增强治疗的分子基础，评估药物的生物利用度、膜通透性和环氧合酶 (COX) 抑制活性。在最后一个具体目标中，我们将评估硬胶囊中 PC-阿司匹林和 PC-布洛芬在存在或不存在流化剂和抗氧化剂的情况下的稳定性，采用封装技术限制 NSAID 与水的接触，特别是对阿司匹林至关重要。上述研究将为我们启动PC-NSAIDs的临床试验和商业化提供所需的重要信息。