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，这使他们有患冠心病的高风险。我们建议开发新的有效和安全的治疗方法，生物聚合物底物作为非全身性高胆固醇药物，具有显著的胆汁酸结合，因此比胆胺具有更好的降胆固醇效果。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的可行性，并通过化学修饰提高其功效。这些材料的胆汁酸结合能力将通过体外试验进行评估。将确定并选择最佳候选者进行随后的体内（动物）筛选。两种最有希望的候选药物在体内的有效性证明。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降胆固醇潜力。安全有效的非全身性高胆固醇药物的鉴定被认为为广大人群提供了显著的治疗益处。建议的商业应用：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效益。

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.