Показано, что совместное введение сополимера N-винилпирролидона и 2-метил-5-винилпиридина и цитостатических препаратов мышам с различными привитыми опухолями повышает эффективность терапии, способствуя увеличению продолжительности жизни. Обнаруженный эффект представляет интерес для дальнейшего изучения возможного использования сополимера в качестве иммуномодулятора при проведении химиотерапии.

Simultaneous administration of a copolymer of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine and cytostatic agents to mice with a variety of implanted tumors was found to increase treatment efficacy, promoting increases in survival time. This effect is of interest for further studies of the possible use of copolymer as an immunomodulator in chemotherapy.

Techniques for quantitative determination of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine copolymers in aqueous solutions were developed. The spectrophotometric technique allowed the copolymer concentration in dilute solutions (0.8 – 1.2 mg/mL) to be determined even in the presence of the interfering additive merthiolate. The refractometric technique was simpler and allowed the copolymer concentration in concentrated solutions (> 1 mass%) to be determined.

The quantitative definition method of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine ratio units in the copolymers using UV-spectrophotometry was developed. Copolymers were prepared by radical copolymerization using azo-bisisobutiric dinitrile as the initiator. On the basе of experimental results and simple mathematical transformations the simplified formula of calculation of the maintenance of 2-methyl-5-vinylpyridine units in the copolymer, including extinction coefficients of poly-2-methyl-5-vinylpyridine and a copolymer sample is concluded. The validity of the method as compared to 13С NMR was shown. According to results obtained by that method the synthesized copolymers are characterized by reproduceable characteristics, in particular the content of 2-methyl-5- vinylpyridine units was found 30-40 mol.%.

It was shown that the traditional methods based on photometry and high performance liquid chromatography cannot be used to determine the content of oligohexamethyleneguanidine hydrochloride in the substance. The alternative methods for the quantitative determination of oligohexamethyleneguanidine hydrochloride in pharmaceutical biocidal substance by refractometry were developed. References 1. Kuznecova L.S. «Polisept» – polimernyj biocid prolongirovannogo dejstvija. – M.: MGUPB, 2001. C.68-153. 2. Skorohodov V.D., Shestakova S.I. Zashhita nemetallicheskih stroitel'nyh materialov ot biokorrozii. – M.: Vysshaja shkola, 2004. S.150-183. 3. Gembickij P.A., Snezhko A.G., Kuznecova L.S., Pantjushenko V.T., Pustovalov I.V., Kolbasov V.P., Topchiev D.A., Borisova Z.S. Sposob poluchenija dezinficirujushhego sredstva. Pat. 2122866 RF; zajavl. 13.04.1998; opubl. 10.12.1998. 4. Lee Y., Cho M.Y., Mo H., Nam K., Koo H., Jin G.-W., Park J.S. / Bul. Corean Chem. Soc. 2008. V.29. №3. P.666-668. 5. Instrukcija №12/05 po primeneniju sredstva «Al'fadez» OOO “Polisept (Rossija) dlja dezinfekcii i predsterilizacionnoj ochistki. – M., 2005. 6. Instrukcija № 12-1/08 po primeneniju dezinficirujushhego sredstva «Al'fadez», OOO «Polisept» (Rossija) dlja dezinfekcii ob#ektov zheleznodorozhnogo transporta i metropolitena. – M., 2008. 7. Matjushina G.P. / Farmacija. 2004. №6. S.32-35. 8. Kedik S.A., Jarcev E.I., Levachev S.M., Panov A.V., Grigor'eva O.A., Zhavoronok E.S., Cherta Ju.V., Zajcev M.A., Ha Kam An' / Him.-farm. zh. 2011. T.45. №3. S.45-49. 9. Heiler D.J. Biguanide composition with low terminal amine: Pat. 0261841 US Pub. Date 23.10.2008. 10. Skorohodova O.N., Voinceva I.I., Kazennov I.V. Kazakova O.M., Dobrohotskij O.N., Borzenkova T.H., Borovik R.V. Sposob prolongirovannoj dezinfekcii pomeshhenij, oborudovanija, konservacii i obezzarazhivanija vody: Pat. №2329286 RF; zajavl. 07.03.2007; opubl. 20.07.2008. 11. Kedik S. A., Sedishev I. P., Panov A. V., Zhavoronok E. S., Ha Kam An'. Razvetvlennye oligomery na osnove proizvodnogo guanidina i soderzhashhee ih dezinficirujushhee sredstvo: Pat. №2443684 RF; zajavl. 13.12.2010; opubl. 27.02.2012. 12. Kedik S.A., Bocharova O.A., Ha Kam An', Panov A.V., Sedishev I.P., Zhavoronok E.S., Timofeeva T.I., Suslov V.V., Beksaev S.G. / Him.-farm. zh. 2010. T.44. №10. S.40-45. 13. Voinceva I.I., Gembickij P.A. Poliguanidiny – dezinfekcionnye sredstva i polifunkcional'nye dobavki. --- M.: LKM-press, 2009. S.36-48. 14. Metodika vypolnenija izmerenij massovoj koncentracii poligeksametilenguanidin-gidrohlorida v pit'evyh prirodnyh i stochnyh vodah fotometricheskim metodom: Sv. ob attestacii metodiki vypolnenija izmerenij № 242/99-09. 30.12.2009. 15. Massovaja koncentracija poligeksametilenguanidin-gidrohlorida v pit'evoj vode. Izmerenie fotometricheskim metodom: Sv. ob attestacii metodiki izmerenij № 08-47/301-01.00143.2011. 16. Sanitarno-jepidemiologicheskaja ocenka bezopasnosti i jeffektivnosti preparata «Dezavid», primenjaemogo dlja dezinfekcii vody plavatel'nyh bassejnov: otchet o vypolnenii NIR. – M.: NII jekologii cheloveka i gigieny okruzhajushhej sredy im. A.N. Sechenova, 2005. --- 53s. 17. Sedishev I.P. Sposob poluchenija dezinficirujushhego sredstva (varianty): Pat. №2223791 RF; zajavl. 10.10.2003; opubl. 20.02.2004 . 18. Kedik S.A., Shatalov D.O., Panov A.V., Suslov V.V., Ha Kam An', Sedishev I.P., Beksaev S.G. / Na styke nauk. Fiz.-him. ser.: mater. I mezhdunar. Internet-konf. – Kazan', 2013. S.143-144. 19. Voinceva I.I., Gembickij P.A. Poliguanidiny – dezinfekcionnye sredstva i polifunkcional'nye dobavki. – M.: LKM-press, 2009. S.38-41. 20. Gosudarstvennaja farmakopeja HІІ izd. T.1. --- M.: NC jekspertizy sredstv medicinskogo primenenija, 2008. S.52-54. 21. Lebedeva M.I. Analiticheskaja himija i fiziko-himicheskie metody analiza. – Tambov: Izd-vo TGTU, 2005. S.96-99. 22. Ioffe B.V. Refraktometricheskie metody himii. – L.: Himija. 1983. S.8-10.

New techniques for the quantitative determination of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine copolymers in aqueous solutions have been developed. The proposed spectrophotometric technique allows one to determine the copolymer concentration in dilute solutions (0.8 – 1.2 mg/ml) even in the presence of an interfering addition – merthiolate. The proposed refractometric technique is simpler and allows one to determine the copolymer concentration in concentrated solutions (>1 mass %).

The solubility in water has been investigated for copolymers of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine with various monomer ratios. Aqueous solutions of the copolymers have low critical mixing temperatures. The solubility of copolymers in water decreases with increasing pH and the concentration of 2-methyl-2-vinylpiridine monomer units. Correlation dependences for predicting the concentration and pH range of the homogeneous solution at the given mixing temperature are determined. The results are useful for the creation of officinal injection preparations based on copolymers of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine.

The water solubility of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine copolymers with various monomer ratios was investigated. Aqueous solutions of the copolymers had low critical mixing temperatures. The water solubility of the copolymers decreased with increasing pH and concentration of 2-methyl-2-vinylpyridine monomers. Correlation dependences for predicting the concentration and pH range of the homogeneous solution at a given mixing temperature were determined. The results were useful for creating injection-ready drug forms based on N-vinylpyrrolidone and 2-methyl-5-vinylpyridine copolymers.

Copolymers of N-vinylpyrrolidone and 2-methyl-5-vinyltetrazole with various ratios of monomer units were synthesized by radical polymerization using the injection method. The copolymerization parameters for these monomers were calculated by the Kelen―Tudos method (r1 = 14.34; r2 = 0.06) for high degrees of conversion. Copolymers with monomer-unit concentrations up to 70 ± 5 mol% were soluble in water, non-toxic, and effective as radioprotectors.

Copolymers of N-vinylpyrrolidone and 2-methyl-5-vinyltetrazole with various ratios of monomer units have been synthesized by radical polymerization using the injection method. The parameters of copolymerization for these monomers were calculated by the Kelen – Tudos method ( r 1 = 14.34; r 2 = 0.06) for high degrees of conversion. Copolymers with the concentration of monomer units up to 70 ± 5 mol. % are soluble in water, non-toxic, and active as radioprotectors.

N-Vinylpyrrolidone and 2-methyl-5-vinylpyridine copolymers with various ratios of monomer units and molecular weights were synthesized by radical copolymerization using an injection method. The ratio of monomer units was determined by non-aqueous potentiometric titration and 13C NMR methods. The viscosity-average molecular weights of copolymers containing 35 – 39 mol% of 2-methyl-5-vinylpyridine were in the range 15.2 – 27.6 kDa. Copolymers with 2-methyl-5-vinylpyridine content up to 75 ± 5 mol% exhibited good solubility in water.

Copolymers of N-vinylpyrrolidone and 2-methyl-5-vinylpyridine with various ratios of monomer units and molecular weights have been synthesized by radical copolymerization using injection method. The ratio of monomer units was determined by nonaqueos potentiometric titration and 13 С NMR methods. The viscosity-average molecular weight of copolymers containing 35 - 39 mol % of 2-methyl-5-vinylpyridine units is within 15.2 - 27.6 kDa. The copolymers with a content of 2-methyl-5-vinylpyridine units up to 75 + 5 mol % exhibit good solubility in water.