Patent ID: 6180598
Filing Date: 2001-01-30
Classification: A61K,C07K

Abstract:
A covalently modified hemoglobin composition having a biooompatible pH and an oxygen binding function, wherein said oxygen binding function has a temperature dependence of less than about 0.023 units per degree Celsius; and wherein said covalently modified hemoglobin composition comprises a hemoglobin intra-molecularly cross-linked by reacting said hemoglobin with a reagent having the formula:X--(CH.sub.2).sub.n CO--Ywherein X is selected from the about consisting of halogen, sulfonate, phosphate, phosphonate, azide, oxirane, thiirane, azirane, malelmide and formyl: n is an integer from 0 to 8; and Y is a substituted activating ester or substituted activating thioester, wherein the activating esters are substituted with at least one anionic group selected from the group consisting of carboxyl, sulfate, sulfide, phosphonate, and phosphate; and having each of at least five thiyl or amino groups on the surface of said hemoglobin covalently joined to a hydrodynamic volume-enhancing, anionic ligand, wherein said ligand has the formula:.sup.- O.sub.2 C--CH.sub.2 --(OCH.sub.2 CH.sub.2).sub.m --O--CH.sub.2 --Zwherein m is an integer from 1 to 100; and Z is CH.sub.2 --Hb, CH(OH)C.sub.2 --Hb, CH(SH)CH.sub.2 --Hb, ##STR3##