Antiatherogenic Properties of tert-Butylhydroquinone

描述（由申请人提供）：动脉粥样硬化是大多数心血管疾病的潜在原因，大量证据支持高胆固醇血症是该疾病的危险因素。在初步工作中，我们发现叔丁基对苯二酚（TBHQ）在低于批准用于人类的剂量下，可以有效降低大鼠模型中总胆固醇和甘油三酯的血浆水平。TBHQ是一种酚类抗氧化剂，常用作食品防腐剂。随后获得了一项专利“降低血液胆固醇和/或血液甘油三酯的方法”。这项研究计划的长期目标是确定thbhq的抗动脉粥样硬化潜力，并推进其商业开发。我们的具体目的是测试thbhq在以下方面的功效：(1)减少主动脉粥样硬化；(2)降低血脂水平；(3)促进少致动脉粥样硬化的脂蛋白谱；(4)降低血浆c反应蛋白（CRP）水平。CRP水平升高是心血管疾病的一个危险因素。在我们的I期实验中，我们将使用apoE敲除（apoE-/-）小鼠模型，因为它已被广泛用于研究其他酚类抗氧化剂的抗动脉粥样硬化潜力。我们的初步市场分析表明，作为降脂剂，thbhq的潜在市场价值为每年1亿美元。由于美国国立卫生研究院已经对四氢大麻酚进行了广泛的毒理学研究，因此商业开发应该加快。

DESCRIPTION (provided by applicant): Atherosclerosis is the underlying cause of most cardiovascular disease and considerable evidence supports the role of hypercholesterolemia as a risk factor for this disease. In preliminary work, we found that tertiary-butyl hydroquinone (TBHQ), at a dose lower than approved for human use, was effective in reducing plasma levels of both total cholesterol and triglycerides in a rat model. TBHQ is phenolic antioxidant commonly used as a food preservative. A patent, "Method for Reducing Blood Cholesterol and/or Blood Triglycerides," was subsequently obtained. The long-term objective of this research proposal is to determine the antiatherogenic potential of TBHQ and advance its commercial development. Our specific aims are to test the efficacy of TBHQ in: (1) reducing aortic atherosclerosis; (2) lowering plasma lipid levels; (3) promoting a less atherogenic lipoprotein profile and; (4) reducing plasma levels of C-reactive protein (CRP). Elevated levels of CRP are a risk factor for cardiovascular disease. In our phase I experiments, we will use the apoE knockout (apoE-/-) mouse model since it has been extensively used to study the antiatherogenic potential of other phenolic antioxidants. Our preliminary market analysis suggests that TBHQ could have a potential market of $100 million per year as a lipid-lowering agent. Commercial development should be accelerated since NIH has already conducted extensive toxicological studies with TBHQ.