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Abstract
OxyVita Hb is a new generation hemoglobin based oxygen carrier (HBOC) produced through modification of a zero-linked polymerization mechanism using activators which incorporate cross-linked bovine tetramer hemoglobin into “super-polymeric” macromolecules (Average molecular weight = 17 MDa) for the purpose of oxygen delivery when whole blood or packed red cells are not available. This molecular design approach was generated in order to address several fundamental biochemical and physiological weaknesses of previous generations of HBOCs. Observation during pre-clinical and clinical studies provided evidence that these early generation acellular HBOCs were directly associated with loss of retention within the circulatory system, extravasation across endothelial tissue membranes due to their small molecular size leading to arterial and venous vasoconstriction with coupled increases in mean arterial pressure (MAP). The inherent increase in molecular size and structural stability of the OxyVita Hb is a direct response to addressing these serious weaknesses that have occurred during the evolution of HBOC development within the past two decades. The nature of the zero-linked synthetic route eliminates any chemical linkers remaining in the product, eliminating side reaction concerns, such as reversibility and decomposition due to weak chemical bonds, dependency on temperature and pressure, and residual toxicity
Highlights
During the past several decades, extensive research efforts have been directed towards the molecular design of an alternate therapeutic oxygen carrier for use in the absence or as an alternative to whole blood or packed red blood cells for the delivery of oxygen in emergency or other clinical applications [1,2,3]
The inherent increase in molecular size and structural stability of the OxyVita Hb is a direct response to addressing these serious weaknesses that have occurred during the evolution of hemoglobin-based oxygen carriers (HBOC) development within the past two decades
The focus of this review is to provide an essential level of information that is presently available about a new generation HBOC, OxyVita Hemoglobin
Summary
During the past several decades, extensive research efforts have been directed towards the molecular design of an alternate therapeutic oxygen carrier for use in the absence or as an alternative to whole blood or packed red blood cells for the delivery of oxygen in emergency or other clinical applications [1,2,3] Most of these approaches have centered upon the development of cell-free (acellular) hemoglobin-based oxygen carriers (HBOC). This approach was associated with increased water of hydration leading to an increase in the effective hydrodynamic radius of these molecular species, reducing the tendency to extravasate These different molecular design modifications resulted in several HBOCs with no observed dimerization and alleviated the initial clinical concern of rapid elimination from the circulation.
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