Development History
The development of PolyHeme® has focused
on its use in the treatment of urgent injury-related hemorrhage.
PolyHeme® is designed to treat hemorrhagic shock where blood
transfusion is required but is not available.
Initially a project of the United States Army following
the Vietnam War, the objective was to develop a preparation that
could be infused rapidly and in massive quantities to injured battlefield
combatants in far-forward areas and mobile surgical theaters before
the injured could be evacuated to more sophisticated field hospitals
for definitive care.
The early development of hemoglobin-based oxygen carriers
(HBOCs) was problematic. Early preparations of unmodified tetrameric
hemoglobin were plagued by renal, hepatic, gastrointestinal, pancreatic,
and cardiovascular toxicities and organ dysfunction. The small molecular-weight
tetrameric species of hemoglobin have been implicated as causative
agents associated with these unacceptable adverse effects. The basis
of these adverse effects has been attributed to vasoconstriction
due to the small molecular-weight tetrameric hemoglobin.
The preparation of PolyHeme®, however, is
designed to avoid these toxicities by removing essentially all vasoactive
tetramer through high-yield polymerization and subsequent filtration
to purify the solution.
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