THERAPEUTIC POLYMERS FOR CARDIOVASCULAR DISEASE

冠心病(CHD)仍然是导致死亡的主要原因。超过5000万美国成年人的血清胆固醇水平很高，这使他们面临着患冠心病的高风险。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，具有显著更强的胆汁酸结合，因此比氯乙四胺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疗效。这些材料的胆汁酸结合能力将通过体外测试进行评估。最好的候选者将被确定和选择用于随后的活体(动物)筛选。两种最有希望在体内展示其疗效的候选药物。这将包括测试以确定：体内胆汁酸的结合能力。抑制血浆胆固醇升高，粪便中性甾醇和胆汁酸排泄，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血症药物的鉴定被认为为广大人群提供了显著的治疗益处。拟议的商业应用：一半的美国成年人口胆固醇水平升高，可能会增加他们患冠心病的风险。发现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.