Diaspirin Crosslinked Hemoglobin (DCLHb^TM)Polymerization

Polymerization of human hemoglobin using the crosslinker 1,11‐bis(maleimido)triethylene glycol for use as an oxygen carrier

“…In fact, PolyhHb was larger in size compared with previously reported PEG‐polymerized Hbs. For example, poly α‐DBBF (diaspirin‐crosslinked Hb polymerized with bis(maleoylglycylamide) PEG) was composed of ∼6.25 Hbs,24, 25 whereas polyDCLHb (diaspirin‐crosslinked Hb polymerized with bis(polysubstituted‐benzenesulfonate ester) PEG) is a heterogeneous HBOC solution composed of Hb multimers 26. The high MW and crosslink density of PolyhHb suggests that infusion of PolyhHb should induce less vasoconstriction and hypertension than either HBOC‐201® or PolyHeme®.…”

Pro-oxidant effects of cross-linked haemoglobins explored using liposome and cytochrome c oxidase vesicle model membranes

“…a-DBBF and fl-DBBF were produced according to [5]. Polya-DBBF, prepared according to [6], was a kind gift from Baxter Corp., IL, U.S.A. All haemoglobin solutions were chromatographed on a DEAE-Sephadex column to ensure removal of catalase, superoxide dismutase and glutathione. The high level of purity of the haemoglobin solutions was confirmed by the use of SDS/PAGE analysis, isoelectric focusing and HPLC.…”

“…Due to these favourable characteristics, a-DBBF has been developed as a blood substitute [5]. Polymerization of a-DBBF by bis(maleolglycylamide)poly(ethylene glycol) (BMMA-PEG), yielding poly-a-DBBF, offers the added benefit of reduced renal clearance and increased retention in the vascular circulation [6].…”

Design of Nonhypertensive Conjugated Hemoglobins as Novel Resuscitation Fluids

“…Designing low oxygen affinity blood substitutes with enhanced molecular size (dimensions) has been initially attempted by one-step oligomerization platform that introduces intra and intermolecular crosslinking using glutaraldehyde. Chang introduced the oligomerization concept (Chang 1964(Chang , 1971, and since then many new bifunctional crosslinkers have been advanced for the oligomerization of Hb (Bunn et al 1969;Payne 1973;Marini et al 1989;D'Agnillo and Chang 1998;Hai et al 1999;MacDonald and Pepper 1994;Hai et al 1994;Bakker et al 1992;Dellacherie and Vigneron 1991;Zhang and Palmer 2010;Faggiano et al 2010;Tarasov et al 2007;Buehler et al 2006;Scurtu et al 2013;Berbers et al 1991;Adachi et al 1991).…”