BIOLOGICALLY STABLE HEPARIN DERIVATIVES

一系列延长的共价肝素-蛋白质复合体 肝素部分和高抗凝血剂的体内半衰期 将开展活动。一系列蛋白质覆盖了广泛的 将选择分子量和等电点的范围 用于这些共轭化合物。不同的共轭技术将是 调查以确定将保留最好的方法 肝素的抗凝血活性。他们的相对能力 共价蛋白质-肝素复合体的催化加速 凝血酶和凝血因子X的抑制作用将通过 停流荧光法。激活部分的延长 凝血活酶时间将用于评估体内的潜力 抗凝血活性。最终但不是作为第一阶段的一部分 研究的半衰期和有效性将在对照中确定 临床研究。

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.