THERAPEUTIC POLYMERS FOR CARDIOVASCULAR DISEASE

冠心病（CHD）仍然是导致死亡的主要原因。超过5000万美国成年人血清胆固醇水平高，使他们处于CHD的高风险中。我们建议开发新的有效和安全的治疗生物聚合物基质作为非全身性高胆固醇血症药物，具有显着更大的胆汁酸结合，因此比考来烯胺更好的降胆固醇疗效。第一阶段的目标是确定使用具有固有降胆固醇特性的生物聚合物并通过化学修饰增强其功效的可行性。将通过体外试验评价这些材料的胆汁酸结合能力。将确定并选择最佳候选物用于随后的体内（动物）筛选。这两种最有希望的候选药物可用于体内证明其疗效。这将包括测定体内胆汁酸结合能力的试验。抑制血浆胆固醇升高、粪便中性固醇和胆汁酸排泄以及候选药物的血浆胆固醇降低潜力。认为安全有效的非全身性高胆固醇血症药物的鉴定可为广大人群提供显著的治疗获益。拟议的商业应用：一半的美国成年人胆固醇水平升高，这可能会增加他们患冠心病的风险。确定一种安全有效的非全身性降胆固醇药物可能具有显著的治疗益处。

Coronary heart disease (CHD) remains a leading cause of mortality. Over 50 million American adults have high serum cholesterol levels that place them at high risk for CHD. We propose to develop new efficacious and safe therapies biopolymer substrates as non-systemic hypercholesterolemic agent with significantly greater bile acid binding and therefore better cholesterol-lowering efficacy than cholestyramine. The objective of Phase I is to determine the feasibility of using biopolymers with inherent cholesterol-lowering properties and enhancing their efficacy by chemical modifications. The bile acid binding capacities of these materials will be evaluated by in vitro testing. The best candidates will be identified and selected for subsequent in vivo (animal) screening. The two most promising drug candidates for in vivo demonstration of their efficacy. This will include tests to determine: in vivo bile acid binding capacity. inhibition of plasma cholesterol elevation, fecal neutral sterol and bile acid excretion, and plasma cholesterol-lowering potential of the drug candidates. The identification of safe and potent non-systemic hypercholesterolemic agents is considered to provide a significant therapeutic benefit to a broad section of the population. PROPOSED COMMERCIAL APPLICATIONS: Half of the adult American population has elevated cholesterol levels that may increase their risk of developing coronary heart disease. The identification of a safe and potent non-systemic cholesterol-lowering drug could be of significant therapeutic benefit.