Low-molecular-weight heparin was synthesized by depolymerization of high-molecular-weight heparin with nitrous acid. Preparative chromatography was used to isolate low-molecular-weight heparins with narrow molecular-weight distributions, as confirmed by size-exclusion HPLC. The average molecular weight of the products according to capillary viscometry decreased with synthesis time (4 h) from 14.0 to 3.4 kDa. Fractions with molecular-weight characteristics, ratios of sulfo- to carboxyl groups, and specific activities corresponding to those of low-molecular-weight heparin isolated from commercially available Fragmin® were isolated among the products. Low-molecular-weight heparins with characteristics analogous to those of Dalteparin and Nadroparin substances could be obtained depending on the treatment time of high-molecular- weight heparin with nitrous acid in acidic medium.
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ACKNOWLEDGMENTS
The work was financially supported by the Ministry of Education and Science of the Russian Federation under the project part of a State Task for 2017 – 2019 (Project 15.2463.2017/4.6).
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 55, No. 3, pp. 43 – 47, March, 2021.
L. E. Frumin is deceased
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Yur’eva, K.P., Frumin, L.E., Baeva, E.A. et al. Molecular Weight Characteristics and Anticoagulant Activity of Low-Molecular-Weight Heparin Obtained By Nitrous Acid Depolymerization. Pharm Chem J 55, 295–299 (2021). https://doi.org/10.1007/s11094-021-02414-z
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DOI: https://doi.org/10.1007/s11094-021-02414-z