ИСТИНА

The use of nanoparticles in medicine is one of the promising directions in the treatment of diseases. Most modern drug substances are solid organic compounds. Various methods of producing organic nanoparticles analyzed in the monograph [1]. We have developed a new strategy that combines obtaining nanoparticles of solid drug compounds with the formation of new crystalline polymorphic structures. The essence of the approach consist in capture of the drug substances molecules by the flow of the heated carrier gas and in subsequent direction of the gas flow to the cold surface (the surface is cooled by liquid nitrogen). The interaction of the flow of carrier gas with the cold surface leads to its sharp cooling. As a result, in the gas phase is achieved a high degree of supersaturation of vapor of drug substance relatively to equilibrium pressure. It provides a homogeneous gas-phase nucleation with the high rate. The subsequent growth of the nanoparticles and the formation of solid phase structures are carried out by capturing of molecules of drug substances from the gas phase. Then, the growing nanoparticles of drug substances reach cold surface of the condenser and immobilized there. The nucleation can also be carried out by the heterogeneous mechanism on the cold surface. The ratio of the contributions of homogeneous and heterogeneous nucleation can be adjusted by varying the experimental parameters. The proposed strategy is applied in the study of tranquilizer phenazepam and steroid neurohormone dehydroepiandrosterone (DHEA). For phenazepam received a new crystalline polymorphic structure, the parameters of which are entered in the Cambridge crystallographic database data [2]. The new structure is stable, has an average particle size of 50 nm. Compared to the original, nano phenazepam has a higher solubility and dissolution rate, characterized by a lower toxicity. Tests on rats have shown that nano phenazepam has increased anxiolytic and reduced sedative and miorelaxant activity [3]. The therapeutic index of nanophenazepam much higher than the original pharmacopoeia one. In the study of DHEA discovered a new polymorphic crystalline nanostructure with a particle size of 100 to 120 nm [4]. We have obtained new -polymorph modification of bioactive antimicrobial substance dioxidine [5]. Strategy cryoformation of new crystalline polymorphic nanostructures does not use solvents, stabilizers and applicable to a large number of poorly soluble modern drug compounds. Our results on phenazepam, DHEA and dioxidine raise the problem of the therapeutic influence the size and solid state structure of the drug substance for the treatment of diseases. The work was made by financial support of RFBR grant No 15-03-05178. [1] Sergeev G.B., Klabunder K.J., Nanochemistry, 2-nd edition, Elsevier 2013, 361 pp. [2] Sergeev G.B., Sergeev B.M., Morosov Yu.N and Chernyshev V.V., Acta Cryst., 2010, E66, 2623. [3] Morosov Yu.N., Kolotilov P.N., Shabatin V.P., Sergeev G.B., Chernyshev V.V., Voronina T.A., Molodavkin G.M., RF Patent No 2440120, 2010. [4] Morosov Yu.N., Utehina A.Yu., Sergeev G.B., Chernyshev V.V., Chistyakov V.V., Goncharov N.P., Rzheznikov V.M., RF Patent No 2528990б, 2013. [5] V.P. Shabatin, O,I.Vernaya, T.I. Shabatina, A.M. Semenov. RF Patent No 2014114406, 2014.