BIOLOGICALLY STABLE HEPARIN DERIVATIVES

生物稳定的肝素衍生物

• 批准号: 3501149
• 负责人: DAISY S MC CANN
• 金额: $ 4.2万
• 依托单位: MC CANN ASSOCIATES, INC.
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-06 至 1987-10-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3501149
• 关键词: anticoagulants; chemical conjugate; chromatography; coagulation factor X; covalent bond; drug metabolism; electrophoresis; heparin; isoelectric point; molecular weight; thrombin; thromboplastin

A series of covalent heparin-protein complexes with prolonged in vivo half lives of the heparin moiety and high anticoagulant activity will be developed. A series of proteins covering a broad range of molecular weights and isoelectric points will be chosen for these conjugates. Various conjugation techniques will be investigated to determine the method which will retain the best anticoagulant activity for the heparin. The relative ability of the covalent protein-heparin complexes to catalytically accelerate the inhibition of thrombin and factor X will be measured by stopped flow fluorimetry. Prolongation of activated partial thromboplastin time will be used to evaluate potential in vivo anticoagulant activity. Ultimately but not as part of the Phase I studies half lives and efficacy will be determined in controlled clinical studies.

一系列肝素-蛋白质共价复合物， 肝素部分和高抗凝剂的体内半衰期 将开展活动。 一系列蛋白质，覆盖广泛的 将选择分子量和等电点的范围 对于这些共轭物。 将使用各种缀合技术。 调查以确定保留最佳的方法 肝素的抗凝活性。 的相对能力 共价蛋白质-肝素复合物， 凝血酶和因子X的抑制将通过以下方法测量 停流荧光法。 活化部分延长 凝血活酶时间将用于评价体内潜力 抗凝血活性 最终但不是作为第一阶段的一部分 研究半衰期和有效性将在对照组中确定。 临床研究。