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吡哆醛化血红蛋白-聚氧乙烯缀合物作为生理性氧载体的特性研究

Characterization of a pyridoxalated hemoglobin-polyoxyethylene conjugate as a physiologic oxygen carrier.

作者信息

Yabuki A, Yamaji K, Ohki H, Iwashita Y

机构信息

Central Research Laboratories, Ajinomoto Co., Inc, Kawasaki, Japan.

出版信息

Transfusion. 1990 Jul-Aug;30(6):516-20. doi: 10.1046/j.1537-2995.1990.30690333482.x.

DOI:10.1046/j.1537-2995.1990.30690333482.x
PMID:2378023
Abstract

A pyridoxalated hemoglobin-polyoxyethylene conjugate (PHP) is an oxygen carrier prepared from outdated human red cells through chemical modifications of hemoglobin (Hb). PHP was evaluated as a physiologic oxygen carrier. PHP was synthesized from a pyridoxalated hemoglobin (PLP-Hb) and an activated diester of polyoxyethylene (POE). The average numbers of molecules of PLP and POE conjugated to a Hb molecule were 3.3 and 6.2, respectively. The p50 of PHP was 20.4 torr, which was much higher than the 14.0 torr of stroma-free Hb. At a Hb concentration of 6 g per dL, PHP had a physiologic colloid osmotic pressure (29 torr) and a lower viscosity (2.6 cP at 37 degrees C) than whole blood (4.2 cP at 37 degrees C). At temperatures below 20 degrees C, the p50 of PHP was higher than that of the red cells. PHP, which had an average molecular weight of 90,000, consisted of 83 percent monomeric PLP-Hb-POE conjugate, 12 percent dimeric PLP-Hb-POE, and 4 percent trimeric PLP-Hb-POE. The consistency of the relative contents of the components was well controlled through seven lots, and each component had sufficient oxygen-carrying capacity. The dimeric and trimeric components contributed to the prolongation of the residence of PHP in the circulation. The results indicate that PHP has favorable properties as an oxygen-carrying blood substitute and perfusate.

摘要

吡哆醛化血红蛋白-聚氧乙烯共轭物(PHP)是一种通过对血红蛋白(Hb)进行化学修饰,由过期人红细胞制备的氧载体。PHP作为一种生理性氧载体进行了评估。PHP由吡哆醛化血红蛋白(PLP-Hb)和聚氧乙烯(POE)的活化二酯合成。与一个Hb分子共轭的PLP和POE分子的平均数量分别为3.3和6.2。PHP的p50为20.4托,远高于无基质Hb的14.0托。在Hb浓度为每分升6克时,PHP具有生理性胶体渗透压(29托),且粘度(37℃时为2.6厘泊)低于全血(37℃时为4.2厘泊)。在低于20℃的温度下,PHP的p50高于红细胞。PHP的平均分子量为90,000,由83%的单体PLP-Hb-POE共轭物、12%的二聚体PLP-Hb-POE和4%的三聚体PLP-Hb-POE组成。通过七批产品,各成分的相对含量一致性得到了很好的控制,且每种成分都具有足够的携氧能力。二聚体和三聚体成分有助于延长PHP在循环中的停留时间。结果表明,PHP作为一种携氧血液替代品和灌注液具有良好的性能。

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