Purification and chemical modifications of hemoglobin in developing hemoglobin based oxygen carriers

被引:56
作者
Haney, CR
Buehler, PW
Gulati, A [1 ]
机构
[1] Univ Illinois, Dept Pharmaceut & Pharmacodynam, Chicago, IL 60612 USA
[2] Univ Illinois, Dept Rehabil Med & Restorat Med Sci, Chicago, IL 60612 USA
[3] Univ Illinois, Dept Bioengn, Chicago, IL 60612 USA
关键词
blood substitutes; cross-linking; polymerization; hypertensive drug effects;
D O I
10.1016/S0169-409X(99)00047-2
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The efficacy of blood substitutes, as a whole, has been readily demonstrated, in animals as well as clinical studies. It is well known that stroma free hemoglobin (SF-Hb) is very toxic, due to effects on renal and coagulation functions and vascular tone. Several modifications have been made to the hemoglobin tetramer in an attempt to eliminate its toxicity. Conjugation, cross-linking, polymerization, and recombinant technology. have all been used to reduce toxicity, while aiming to optimize the therapeutic value of hemoglobin based blood substitutes. The remaining issue seems to be the hypertensive response seen: in many hemoglobin solutions. The cause of the hypertensive response, and hence what chemical modifications are suitable to alleviate it are still under debate. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:153 / 169
页数:17
相关论文
共 94 条
[31]  
Gould SA, 1996, WORLD J SURG, V20, P1200
[32]  
Gulati A, 1997, Expert Opin Investig Drugs, V6, P1659, DOI 10.1517/13543784.6.11.1659
[33]   DIASPIRIN CROSS-LINKED HEMOGLOBIN (DCLHB(TM)) - INVOLVEMENT OF ADRENERGIC-MECHANISMS IN THE PRESSOR EFFECT [J].
GULATI, A ;
REBELLO, S .
ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY, 1994, 22 (03) :603-612
[34]   Role of endothelin in the cardiovascular effects of diaspirin crosslinked and stroma reduced hemoglobin [J].
Gulati, A ;
Sharma, AC ;
Singh, G .
CRITICAL CARE MEDICINE, 1996, 24 (01) :137-147
[35]   PRAZOSIN BLOCKS THE PRESSOR BUT NOT THE REGIONAL CIRCULATORY EFFECTS OF DIASPIRIN CROSS-LINKED HEMOGLOBIN [J].
GULATI, A ;
SHARMA, AC .
LIFE SCIENCES, 1994, 55 (02) :121-130
[36]   DIASPIRIN CROSS-LINKED HEMOGLOBIN (DCLHB(TM)) POLYMERIZATION [J].
HAI, TT ;
NELSON, D ;
PEREIRA, D ;
SRNAK, A .
ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY, 1994, 22 (03) :923-931
[37]  
HEIN LG, 1988, CIRC SHOCK, V26, P353
[38]   SYSTEMIC AND PULMONARY-HYPERTENSION AFTER RESUSCITATION WITH CELL-FREE HEMOGLOBIN [J].
HESS, JR ;
MACDONALD, VW ;
BRINKLEY, WW .
JOURNAL OF APPLIED PHYSIOLOGY, 1993, 74 (04) :1769-1778
[39]  
HSIA JC, 1997, Patent No. 5591710
[40]  
HSIA JC, 1989, Patent No. 4857636