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羟乙基淀粉的研究。第一部分:尺寸排阻色谱结合低角度激光光散射的分子表征

Studies on hydroxyethyl starch. Part I: Molecular characterization by size exclusion chromatography coupled with low-angle laser light scattering.

作者信息

Lederer K, Huber C, Dunky M, Fink J K, Ferber H P, Nitsch E

出版信息

Arzneimittelforschung. 1985;35(3):610-4.

PMID:2581590
Abstract

Two commercially available hydroxyethyl starch (HES) preparations (in clinical use as plasma expanders) specified with Mw = 450,000/MS = 0.7 and Mw = 200,000/MS = 0.5, respectively, and three experimental HES-samples (supposingly similar to the commercial product with the specification 450,000/0.7, except of one with MS = 0.5) were studied. The latter were prepared via acid or enzymatic hydrolysis of waxy-maize starch. Each of the samples was characterized by its intrinsic viscosity and molar substitution, and was studied with low-angle laser light scattering (LALLS) and with size exclusion chromatography (SEC) coupled with LALLS. The weight-average molecular weight Mw of the commercial samples was found to be 60-80% higher than the value given in the product declaration. This discrepancy can be explained by the argument that previous measurements were not carried out at sufficiently small scattering angles to enable reliable extrapolation to zero angle. The calibration functions Mw(v) of the individual HES-samples measured by SEC/LALLS-coupling are identical over a broad range of the elution volume v and are used for calibration of conventional SEC in a subsequent paper. The small, but detectable differences in the Mw(v)-functions indicate interesting differences between these HES-preparations with respect to the effective hydrodynamic density of the branched HES-molecules.

摘要

研究了两种市售羟乙基淀粉(HES)制剂(临床上用作血浆扩容剂),其特性分别为Mw = 450,000/MS = 0.7和Mw = 200,000/MS = 0.5,以及三种实验性HES样品(假定与规格为450,000/0.7的市售产品相似,其中一种MS = 0.5除外)。后者通过糯玉米淀粉的酸水解或酶水解制备。每个样品通过其特性粘度和摩尔取代度进行表征,并采用低角度激光光散射(LALLS)以及与LALLS联用的尺寸排阻色谱法(SEC)进行研究。发现市售样品的重均分子量Mw比产品声明中给出的值高60 - 80%。这种差异可以用以下观点来解释:先前的测量没有在足够小的散射角度下进行,无法可靠地外推至零角度。通过SEC/LALLS联用测量的各个HES样品的校准函数Mw(v)在洗脱体积v的很宽范围内是相同的,并在后续论文中用于常规SEC的校准。Mw(v)函数中微小但可检测到的差异表明这些HES制剂在支链HES分子的有效流体动力学密度方面存在有趣的差异。

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引用本文的文献

1
Pharmacokinetics of hydroxyethyl starch.羟乙基淀粉的药代动力学
Clin Pharmacokinet. 2005;44(7):681-99. doi: 10.2165/00003088-200544070-00002.
2
Mechanisms of postoperative prolonged plasma volume expansion with low molecular weight hydroxethy starch (HES 200/0.62, 6%).低分子量羟乙基淀粉(HES 200/0.62,6%)导致术后血浆容量长期扩张的机制
Intensive Care Med. 1995 Jul;21(7):577-83. doi: 10.1007/BF01700163.
3
Clinical pharmacokinetic considerations in the use of plasma expanders.血浆扩容剂使用中的临床药代动力学考量
Clin Pharmacokinet. 1987 Feb;12(2):123-35. doi: 10.2165/00003088-198712020-00003.