@article{oai:air.repo.nii.ac.jp:00000922,
 author = {TSUCHIDA, Eishun},
 issue = {1},
 journal = {International Journal of the Society of Materials Engineering for Resources},
 month = {Mar},
 note = {Since the discovery of a red-colored saline solution of a heme derivative that reversibly binds and releases O2 (1983), significant efforts have been made to realize an O2 infusion as a red cell substitute based on the sciences of both molecular assembling phenomena and macromolecular metal complexes. We have specified that hemoglobin (Hb)-vesicles (HbV) and recombinant human serum albumin -hemes (rHSAhemes) would be the best systems that meet the clinical requirements. The HbV encapsulates ultrapure cone. Hb solution, that is free of any infectious elements, with a phospholipid bimolecular membrane (diameter, 250nmφ), and its solution properties can be adjusted comparable with blood. Surface modification of HbV with a water-soluble polymer ensures stable dispersion state and storage over a year at 20°C. In vivo tests have clarified the efficacy for extreme hemodilution and resuscitation from hemorrhagic shock, and safety in terms of biodistribution, metabolism in RES, clinical chemistry, blood coagulation, etc.. The HbV does not induce vasoconstriction thus maintains blood flow and tissue oxygenation. The rHSAheme is a totally synthetic O2 carrier that incorporates 8 heme derivatives (axial base substituted hemes) as O2 binding sites in the hydrophobic pockets of rHSA, which is now manufactured in Japan as a plasma-expander. Hb binds endothelium-derived relaxation factor, NO, and induces vasoconstriction. The rHSA-heme binds NO as Hb does, however, it does not induce vasoconstriction due to its low pI (4.8) and the resulting low permeability across the vascular wall (1/100 of Hb). A 5%-albumin solution possesses a physiologic oncotic pressure. Therefore, to increase the 02-transporting capacity, albumin dimer is effective. Albumin dimer can incorporate totally 16 hemes with a regulated oncotic pressure. The rHSA-heme is effective not only as a red cell substitute but also for O2 therapeutics (e.g., oxygenation for tumor). Significant efforts have been made to produce HbV and rHSA-hemes with a facility of GMP standard, and to start preclinical and finally clinical trials.},
 pages = {1--11},
 title = {Evaluation of Safety and Efficacy of Hemoglobin-Vesicles and Albumin-Hemes},
 volume = {12},
 year = {2004}
}