Preparation of a novel double polymerized of red blood cell substitute and preliminary observation of its curative effect

Abstract

Objective To study the red blood cell substitute preparation method of glutaraldehyde(GDA) and Bis(3, 5-dibromosalicyl) fumarate(DBBF) double polymerized, and also observe its curative effect. Methods The affecting factors of the crosslink of DBBF and human placental hemoglobin(Hb) were selected, including solution pH, inositol hexaphosphoric acid concentration, and molar ratios of DBBF/Hb. The changes of P50, Hill Co and methemoglobin(MetHb) content during the preparation process were studied and the molar ratio of GDA to DBBF-Hb were determined. The final product was obtained through the steps of ultrafiltration, filtration, and deoxygenation, etc., and the final product was subjected to a study on the curative effect of anti-hemorrhagic shock in rats. Results Under the condition of pH 8.0, the concentration of inositol hexaphosphoric acid was 10mM/L, the molar ratio of DBBF/hemoglobin was 6∶1, the content of dimer was(22.67±3.28)%, the content of tetramer was (74.64±7.05)%, and its P50 was (25.25±2.31) mmHg. As the molar ratio of DBBF/Hb increased, P50 and MetHb content would gradually increase, while the Hill Co will gradually decrease. The molar ratio of GDA and DBBF-Hb was 7∶1, the content of dimer was (8.23±0.79)%, the content of tetramer was (27.87±3.63)%, the content of super-macromolecule was (1.05±0.31)%. As the molar ratio of GDA and DBBF/Hb increased, MetHb content would increase, while the P50 and Hill Co would gradually decrease. The 24h survival rate of the product in rats with hemorrhagic shock was 83.33%(10/12), which was significantly higher than that in the negative control group[41.67%(5/12)], while similar with the positive control group [91.67%(11/12)]. Conclusion The red blood cell substitutes with GDA and DBBF double polymerized can effectively reduce the dimer content, which is more conducive to industrial production, and has a positive effect on the treatment of hemorrhagic shock.

Keywords

• glutaraldehyde(gda)
• dbbf
• dual polymerization
• red blood cell substitute
• p50