A Starch-Hemoglobin Resuscitative Compound

Abstract

A resuscitative compound in freeze-dried form has been synthesized between a modified starch and a tetremerically stabilized hemoglobin. In order to complex the hemoglobin, the starch has been prepared in mono-, di-, tri-, and tetra-aldehyde moieties. The hemoglobin was stabilized with low molecular weight diacids. Electrophoretic densitometric patterns indicate compound formation. The resulting polymers were characterized with respect to oxygen transport (biotonometry), Hill constant and P50. The in vivo evaluation indicates that these compounds are effective in exchange-transfusion experiments with rats to a level of about 85% replacement of whole blood. The final product is a cost-effective acellular resuscitative compound which can be stored in freeze-dried form at room temperature for extended periods of time. This artificial blood substitute can be reconstituted upon the addition of water.

Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some PhysiologyBlut ist ein ganz besondrer Saft

“…Hydroxyethylstarch was derivatized with cyanogen bromide, ethylene diamide, and glutaraldehyde and oxidized with NaIO 4 in view of producing HES−Hb conjugates. , Significant cross-linking was observed, yielding viscous heterogeneous products with increased O 2 affinity . In a further rather complicated seven-step approach, an aldehyde-derivatized HES obtained by treatment, first with cyanogen bromide, then with a di-, tri-, or tetraamine, then with glutaraldehyde, was further oxidized with NaIO 4 ; the resulting polyaldehyde mixture was eventually allowed to react with Hbs that had already been cross-linked intramolecularly with EDCI-activated glyoxylic, glutaric, or adipic acids, followed by NaBH 4 reduction . More recently a Hb−HES conjugate was obtained from cyanogen bromide-activated HES in somewhat different conditions .…”

“…834 In a further rather complicated seven-step approach, an aldehyde-derivatized HES obtained by treatment, first with cyanogen bromide, then with a di-, tri-, or tetraamine, then with glutaraldehyde, was further oxidized with NaIO 4 ; the resulting polyaldehyde mixture was eventually allowed to react with Hbs that had already been crosslinked intramolecularly with EDCI-activated glyoxylic, glutaric, or adipic acids, followed by NaBH 4 reduction. 835 More recently a Hb-HES conjugate was obtained from cyanogen bromide-activated HES in somewhat different conditions. 836 The Hb concentration of solutions of such conjugates was limited by viscosity, and mixtures with RBCs resulted in a kind of sludge that indicated strong interaction with RBCs.…”