Оптимизация первой стадии синтеза эноксапарина методом гидролитической деполимеризации нефракционированного гепарина

The first step of low-molecular-weight heparin (enoxaparin) preparation by hydrolytic depolymerization of unfractionated heparin was investigated. This step involves the chemical reaction of initial heparin and benzethonium chloride in aqueous-saline solution. It is established that increased concentration of unfractionated heparin leads to greater number of acid equivalents determined. Probably, there is a relationship between the ionic strength of solution and conformation of heparin macromolecule. This was confirmed by method of dynamic light scattering: the average size of light scattering centers in aqueous solution of heparin decreases with increasing sodium chloride concentration. It is found that, in order to increase the rate of benzethonium heparinate cleaning from starting reagents and decrease the volume of washing solution, it is better to use water without sodium chloride and employ ultrasonication. Compositions of synthesized and purified benzethonium heparinate samples were determined using 1 H NMR.