Hemoglobin solutions coupled with polyethylene glycol 1900: preparation, purification, quality control and pharmacological trials by hemorrhagic shock

Abstract

The usefulness of hemoglobin solutions as oxygen transporters is limited by their high affinity for oxygen and rapid elimination from the circulation. Various chemical modifications of hemoglobin aimed at overcoming these two handicaps have been suggested. We have developed a conjugate of pyridoxylated human hemoglobin with monomethoxypolyoxyethtylene 1900, whose preparation and properties are described. We present comparative results on short-term or definitive survival of Wistar rats which, during hemorrhagic shock due to the loss of 60 or 80% of their blood mass, were given a solution of native or modified hemoglobin, in some cases purified by ion-exchange chromatography to remove non-heme proteins, lipids, and some endotoxins. The more complex the treatment used to improve the properties and the purity of the hemoglobin solutions, the longer the animals survived. The loss of hemoglobin in the urine was greatly reduced after conjugation: after 20 h, less than 6% of the total infused.