Development of polyethyleneglycol-conjugated bovine hemoglobin derivative

The development of hemoglobin-based acellular red cell substitute having low oxygen affinity was achieved by pyridoxalation of bovine hemoglobin (HbBv). The subsequent polyethyleneglycol conjugation prolonged circulatory half-life time (T1/2). The final product showed an extremely low oxygen affinity (P50=44.48 mmHg at 37°C). When the hemoglobin derivative (5 g/dl) was infused into rats by bolus injection at 20 ml/kg, T1/2 was 13 hr. indicating that the PEG-conjugation increased T1/2 by 8.6 times in comparison with unmodified HbBv. The PEG-conjugated pyridixalated HbBv is characterized as a unique derivative having an extremely reduced oxygen affinity and a prolonged intravascular retention. These properties make this product a promising new candidate for red cell substitute and plasma expander having an improved oxygen transporting capacity.