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- W3175997908 abstract "The pharmaceutical heparin is a complex polysaccharide of the glycosaminoglycan family, usually derived from porcine mucosa, and is a mainstay of anticoagulant therapy worldwide. Its activity can be modified, most notably, through depolymerisation. Yet, owing largely to the chain complexity, the progressive effects of environmental conditionson the heparin structure have not been fully described. A systematic study of the progressive effects of acidic and alkaline hydrolysis on heparin chain length and sulfate substitution has therefore been conducted. The initial analysis concerned the changes of weight-average molecular weight of heparin, induced by applied conditions. In acidic environments, the relation between the molecular weight loss and pH was inversely correlated, whilst the rate of degradation increased with temperature. In alkaline environments, the molecular weight loss was proportional to pHand temperature, although less effective.Under milder acidic conditions, desulfation was the major factor affecting the molecular weight of the polysaccharide, whilst in alkaline conditions, the hydrolytic sulfate scission was not as prominent. Glycosidic scission was observed only after the prolonged hydrolytic processing at pH 1, at 80 C. Stability studies confirmed the chain stability between pH 2 and pH 12.To understand desulfation order and further investigate possible rearrangements, selected acid and alkaline hydrolysates were monitored via 2D (HSQC) NMR. This study revealedthat in acidic environments all sulfate groups of heparin were altered. It was observed that the sulfate groups were hydrolytically removed in the following order: N-sulfate (NS-), then 2-O-sulfate (2OS-), and finally 6-O-sulfate (6OS-), although the selectivity of last two was strongly dependent upon applied conditions. On the other hand, the NMR analysis of alkali treated heparin demonstrated that applied environments catalysed only iduronatedesulfation (2OS-), followed by its exclusive rearrangements to a galacturonic residue. The research discussed in this thesis investigated the behaviour of heparin in aqueous systems altered by temperature and pH over time. The selected stressing factors closely resembled conditions applied over the industrial and/or pharmacological processing. Therefore, the contribution of presented findings reaches beyond theoretical knowledge and extends to possible practical applications, i.e., optimisation of manufacturing, storage and administration of pharmacologically active heparin products." @default.
- W3175997908 created "2021-07-05" @default.
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- W3175997908 date "2021-04-01" @default.
- W3175997908 modified "2023-09-24" @default.
- W3175997908 title "Study of Hydrolytic Degradation of Heparin in Acidic and Alkaline Environments" @default.
- W3175997908 hasPublicationYear "2021" @default.
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