Preclinical biology of recombinant human hemoglobin, rHB1.1

被引:18
作者
Zuckerman, SH [1 ]
Doyle, MP
Gorczynski, R
Rosenthal, GJ
机构
[1] Lilly Res Labs, Div Cardiovasc Res, Indianapolis, IN 46285 USA
[2] Somatogen Inc, Boulder, CO 80301 USA
来源
ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY | 1998年 / 26卷 / 03期
关键词
D O I
10.3109/10731199809117456
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Historically, the development of hemoglobin based oxygen carriers, HBOCs, were confounded by issues related to activation of the complement cascade and other inflammatory processes, renal toxicity, and significant systemic vasoconstriction. However, with shortages in the blood supply, the risk of infectious agent contamination, and delays associated with complete crossmatch as well as transfusion reactions, HBOC development has assumed greater importance. A successful HBOC in addition to having favorable oxygen binding parameters and colloid oncotic properties, must also have a low toxicity profile, be nonimmunogenic, have positive theologic properties, and have an adequate in vivo half life. In addition, it must also be stable in vivo and not undergo significant oxidation to methemoglobin or release heme or iron in the vasculature. The preclinical studies which have been designed and executed to address these requirements for recombinant human hemoglobin rHb1.1serve as the focus of this review. Recombinant Hb1.1represents the first HBOC to enter clinical trials as a recombinant product in distinction to other HBOCs which are derived from bovine or outdated human blood. While currently in phase II clinical trials, the preclinical biology which has increased our understanding of this molecule are the subject of this review.
引用
收藏
页码:231 / 257
页数:27
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