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- Title
Optimization of the First Step of Enoxaparin Synthesis by Hydrolytic Depolymerization of Unfractionated Heparin.
- Authors
Frumin, L. E.; Yur'eva, K. P.; Askretkov, A. D.; Prokhorov, D. I.; Matveev, A. V.; Zhavoronok, E. S.; Panov, A. V.; Shatalov, D. O.; Shnyak, E. A.; Kedik, S. A.
- Abstract
The first step of low-molecular-mass heparin (enoxaparin) preparation by hydrolytic depolymerization of unfractionated heparin was investigated. The step involved chemical reaction of starting heparin and benzethonium chloride in aqueous saline solutions. The number of acid equivalents in unfractionated heparin was shown to increase as the NaCl concentration increased. This was probably related to effects of the solution ionic strength on the heparin macromolecular conformation, which was confirmed using dynamic light scattering. The average size of the observed light-scattering centers in aqueous heparin solutions decreased with increasing NaCl concentration. Rinsing with H2O and not NaCl solutions and application of ultrasonication were recommended to accelerate purification of benzethonium heparinate from starting materials and to reduce the amount of rinse water. The compositions of the produced and purified benzethonium heparinate samples were confirmed using PMR spectroscopy.
- Subjects
ENOXAPARIN; HYDROLASES; DEPOLYMERIZATION; POLYSACCHARIDES; AQUEOUS solutions
- Publication
Pharmaceutical Chemistry Journal, 2018, Vol 52, Issue 8, p735
- ISSN
0091-150X
- Publication type
Article
- DOI
10.1007/s11094-018-1893-3