Copolymers of N-vinylpyrrolidone
Copolymers based on N-vinylpyrrolidone are widely used in medicine and are of great interest as physiologically active substances for medicinal purposes. However, the synthesis of such copolymers is difficult because, in addition to controlling the molecular weight, it is necessary to control compositional homogeneity. A number of monomers (for example, vinylpyridines and styrene) have a relatively low reactivity when copolymerized with N-vinylpyrrolidone: their copolymerization constants are much less than unity (see table). To obtain such copolymers with a stable composition, a copolymerization method with maintaining a constant ratio of comonomer concentrations during the entire synthesis is promising (the “feed method”). Synthesis control is carried out by periodic sampling of the reaction mixture and their analysis by high performance liquid chromatography (HPLC). The result is copolymers with a narrow compositional distribution.
Copolymerization constants of N-vinylpyrrolidone (r1) with vinylpyridines and styrene (r2)
Copolymers of N-vinylpyrrolidone with 2-methyl-5-vinylpyridine exhibit pronounced physiological activity, which increases with an increase in the proportion of 2-methyl-5-vinylpyridine units, while an increase in the proportion of N-vinylpyrrolidone units improves the solubility of the copolymer in water. Copolymer 64 has optimal properties. mol% N-vinylpyrrolidone and 36 mol% 2-methyl-5-vinylpyridine with Mw = 46.6 kDa.
The Company’s specialists have synthesized and isolated copolymers of N-vinylpyrrolidone with 2-methyl-5-vinylpyridine in a wide range of ratios of starting monomers. The copolymerization constants for this pair of monomers are r1= 13.0 and r2= 0.039 (index 1 refers to 2-methyl-5-vinylpyridine). The features of the solubility of copolymers of N-vinylpyrrolidone with 2-methyl-5-vinylpyridine in water at various temperatures, solution concentrations, and pH have been studied in detail. Photometric and refractometric methods have been developed for the quantitative determination of copolymers of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine in aqueous solutions.
These methods make it possible to determine the content of the copolymer both in concentrated (>1 wt%) and diluted (0.8-1.2 mg / ml) solutions, including in the presence of interfering additives.
Preclinical studies on various animal species have shown that copolymers of N-vinylpyrrolidone with 2-methyl-5-vinylpyridine are non-toxic and biologically active. When used as an immunoadjuvant in the composition of various vaccines, an increase in the effectiveness of the vaccine (depending on its nature) by 2 or more times has been established. Copolymers increase the phagocytic activity of macrophages and other parameters of phagocytosis. The combined use of these copolymers with chemotherapy drugs (cytostatics) increases the antitumor effect on various models of cancer tumors. In addition, copolymers of N-vinylpyrrolidone with 2-methyl-5-vinylpyridine can serve as a prolonged action additive in ophthalmic preparations, for example, in taurine-based drops. Solutions of Sovidon during instillation show a moderately pronounced restorative effect in relation to the damaged epithelium of the cells of the cornea of the eye. The introduction of Sovidon, which has its own biological activity, into the drug Taufon increases the overall effectiveness of the latter, and also contributes to its prolonged action, which will reduce the frequency of instillations and the duration of the course of therapy. Compared with other polymeric modifiers (dextran or polyhexamethylene guanidine hydrochloride), aqueous solutions of taurine with a copolymer have increased efficiency. Their use as a base for eye drops does not damage the lipid layer of the tear film, so that when the function of the lacrimal glands is restored, the urgently formed polymer film can be successfully replaced with a natural lipid film due to natural processes.
