Feinstruktur und Hyperfeinstruktur von klinisch verwendeter Hydroxyethylstärke

Sommermeyer, K.; Hildebrand, U.; Cech, Franz; Pfitzer, E.; Henning, Klaus; Weidler, B.

doi:10.1002/star.19920440504

Cited by 8 publications

(6 citation statements)

References 14 publications

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“…To characterize the substitution of starch with hydroxyethyl units, two terms are used in the literature, namely the degree of substitution (DS hydroxyethyl ) and the molar substitution (MS hydroxyethyl ). The definition of these terms in the literature is not unequivocal, and they are often interchanged, leading to confusion. − In this manuscript, MS hydroxyethyl is defined as the average number of hydroxyethyl groups per anhydroglucose unit (AGU), while DS hydroxyethyl represents the fraction of substituted AGU (regardless whether they have single or multiple substitutions) …”

Section: Introductionmentioning

confidence: 99%

“…The definition of these terms in the literature is not unequivocal, and they are often interchanged, leading to confusion. [11][12][13] In this manuscript, MS hydroxyethyl is defined as the average number of hydroxyethyl groups per anhydroglucose unit (AGU), while DS hydroxyethyl represents the fraction of substituted AGU (regardless whether they have single or multiple substitutions). 12 Hydroxyethylation imparts a number of desirable properties to starch, namely an increase in solubility and solution stability, and more importantly, an increase in the in vivo half-life.…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13] In this manuscript, MS hydroxyethyl is defined as the average number of hydroxyethyl groups per anhydroglucose unit (AGU), while DS hydroxyethyl represents the fraction of substituted AGU (regardless whether they have single or multiple substitutions). 12 Hydroxyethylation imparts a number of desirable properties to starch, namely an increase in solubility and solution stability, and more importantly, an increase in the in vivo half-life. 11,14 The latter is of the order of only a few minutes for native starch due to rapid degradation by serum amylases.…”

Section: Introductionmentioning

confidence: 99%

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Hydrophobically Modified Hydroxyethyl Starch: Synthesis, Characterization, and Aqueous Self-Assembly into Nano-Sized Polymeric Micelles and Vesicles

et al. 2007

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Hydroxyethyl starch (HES) is a water soluble semisynthetic polysaccharide that is used as a plasma volume expander and cryoprotectant. In order to produce a fully biodegradable amphiphilic polymer, HES was esterified with lauric, palmitic, and stearic acids under mild reaction conditions using dicyclohexyl carbodiimide (DCC) and dimethylaminopyridine (DMAP). The molar substitution of the acyl chains (MSfatty acid) was determined with 1H NMR spectroscopy, while the conformational state of the hydrocarbon chains in the graft copolymer was determined using Raman spectroscopy. Furthermore, the aqueous self-assembly of the modified polymer was studied using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Results show the formation of 20 to 30 nm micelles, and 250 to 350 nm polymeric vesicles. Electron spin resonance (ESR) spectroscopy was used to study the microenvironment of a hydrophobic spin probe loaded inside the formed nanodispersion. It was possible to identify the location of the probe and its distribution between the micelles and vesicles. Finally, the hydrophobically modified HES might find use as a potential drug carrier, warranting the future investigation of its ability to encapsulate and deliver drug candidates.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hydrophobically Modified Hydroxyethyl Starch: Synthesis, Characterization, and Aqueous Self-Assembly into Nano-Sized Polymeric Micelles and Vesicles

et al. 2007

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“…Substitution with hydroxyethyl groups significantly delays the enzymatic hydrolysis of starch. It is known that α-amylase can only hydrolyze glycosidic bonds of unsubstituted glucose units [5]. A lower degree of substitution denotes a larger number of unsubstituted regions in an HES molecule that are more easily accessible to enzymatic degradation.…”

Section: Plos Onementioning

confidence: 99%

Changes in the degree of substitution of HES in vivo and their influence on methods for determining HES concentrations in plasma

Lukasewitz,

Rischer,

Schedel

et al. 2023

PLoS ONE

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Objective The degree of substitution (DS) of HES describes the average proportion of substituted glucose molecules in a starch molecule. Although no quantitative studies of the in vivo behavior of the DS have been conducted so far, most pharmacokinetic studies to date have measured HES concentrations using the enzymatic method. This method assumes that at any point in time after an infusion, the DS in a serum remains constant and is identical to the DS in the infused solution. In the present study, we examined the changes in the DS of HES 130/0.42 in vivo in an animal model and compared two methods of measuring HES concentrations in plasma (the enzymatic and the o-Toluidine method). Methodology We randomized 22 pigs into 2 groups. After induction of anesthesia, the pigs received 500 ml or 1000 ml of HES 130/0.42 (Tetraspan®). The DS was measured directly after the infusion, then after 30, 60, 120 and 240 minutes. In determining the DS, the hydroxyethyl starch was extracted from the plasma and hydrolyzed with hydrochloric acid to form non-substituted glucose and hydroxyethyl glucose. Subsequently, the concentration of free unsubstituted glucose was determined enzymatically and the total concentration of all (i.e., substituted and unsubstituted) glucose molecules was determined using the o-Toluidine method. From this, the concentration of the substituted glucose (hydroxyethyl glucose) and the DS could be calculated. In addition, the HES concentration was measured first in vitro and then in vivo at any point after the infusion by both the enzymatic method and the o-Toluidine method. Results The DS increased significantly directly after the infusion from 0.42 to 0.53 (for 500ml) or to 0.50 (for 1000ml); 4 hours later this had further increased to 0.55 and 0.54, respectively (p <0.0001). The HES concentration in vitro showed no significant difference (p = 0.17) when determined with the enzymatic and the o-Toluidine method. In contrast, the serum concentrations in vivo displayed significant differences (p<0.0001) between the two measurement methods. Immediately after the infusion of 500ml HES, the concentration measured with the o-Toluidine method was 31% higher than the one measured with the enzymatic method; 4 hours later, this discrepancy was still at 25%. For 1000 ml HES, the differences amounted to 16% and 25%, respectively. Conclusion The DS of HES in vivo increases significantly over time. As a result, an HES concentration measured with the enzymatic method in vivo will be significantly lower than the same concentration determined with the o-Toluidine method. In future pharmacokinetic studies, HES concentrations should be measured using a method that takes into account changes in the DS in vivo.

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“…Bislang konnten die Strukturparameter von klinisch verwendeter Hydroxyethylstarke bezuglich Substitution und Verzweigung nur als statistische Durchschnittswerte einer HES-Probe angegeben werden. Dabei kann neuerdings auch nach der Substitutionsposition an den Anhydroglucosen sowie nach ihren Bindungsarten differenziert werden [4]…”

Section: Diskussionunclassified

Chromatographische Untersuchungen zur Polydispersität von Hydroxyethylstärke

et al. 1992

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Eine repräsentative Probe von einer klinisch verwendeten Hydroxyethylstärke wurde mittels semipräparativer HPGPC in enge Molekulargewichtsfraktionen im Bereich von ca. 3 000 bis 800 000 D aufgetrennt. Ausgangsprobe und ausgewählte Einzelfraktionen wurden durch gaschromatographische Methylierungsanalyse in bezug auf die Substitutionsgrade MS und DS charakterisiert, wobei diese nach Substitutionsposition C2, C3 und C6 der Anhydroglucosen und deren glycosidische Bindungsart α‐1, α‐1,4 bzw. α‐1,4,6 unterschieden wer‐den. Ebenfalls ermittelt wurde die Polydispersität in bezug auf die Verzweigung. Weiterhin werden die durch Multidetektions‐HPSEC ermittelten Kenngrößen zur Molekulargewichtsverteilung und die Mark‐Houwink‐Parameter angegeben. Die Daten zeigen insgesamt eine weitgehende Homogenität der Ausgangsprobe in bezug auf die gemessenen Parameter. Ihre klinische Relevanz wird diskutiert.

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Feinstruktur und Hyperfeinstruktur von klinisch verwendeter Hydroxyethylstärke

Cited by 8 publications

References 14 publications

Hydrophobically Modified Hydroxyethyl Starch: Synthesis, Characterization, and Aqueous Self-Assembly into Nano-Sized Polymeric Micelles and Vesicles

Hydrophobically Modified Hydroxyethyl Starch: Synthesis, Characterization, and Aqueous Self-Assembly into Nano-Sized Polymeric Micelles and Vesicles

Changes in the degree of substitution of HES in vivo and their influence on methods for determining HES concentrations in plasma

Chromatographische Untersuchungen zur Polydispersität von Hydroxyethylstärke

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