ИСТИНА

Modern drugs are complex organic compounds and they are often poorly soluble in water. Special methods and nanotechnologies were developed to obtain drug nanofoms. The most widely used methods are laser ablation, mechanical grinding, reprecipitation methods, o/w emulsion, supercritical fluids, etc.[1,2]. Traditionally these methods consider using various organic solvents. We have developed and patented a cryochemical technology of synthesizing nanoforms of crystalline organic drug substances without solvents. The technology includes the following stages: dynamic transition of the original crystalline substance into the gas-phase state by programmed evaporation in a flow of heated gas-carrier, organization of the directional vapor flow to a liquid-nitrogen-cooled surface, achieving temperature gradients suitable for homogeneous nucleation, transformation of these nucleuses into nanostructures, condensation and stabilization. The task of obtaining a new phenazepam (7-bromo-1,3-dihydro-5-(2-chlorophenyl)-2H-1,4-benzodiazepine-2-one) nanostructure was solved with the use of the proposed technology. Crystallographic parameters of the new cryochemical nanomodification of original pharmacopoeia phenazepam are entered into the international Cambridge Structural Database[3]. Physicochemical properties of the new structure were studied by different methods. The new β-modification of phenazepam is shown to be stable, it has the average particle size of 50 nm. As compared to the original drug, this modification is characterized by lower toxicity, better solubility and higher solubility rate. Tests with rats demonstrate that compared to the original substance, the new modification exhibits enhanced anxiolytic activity and lower sedative and muscle relaxation effects[4]. Therapeutic index of the cryophenazepam is appreciably higher than the index of pharmaceutical phenazepam. The developed method has been also applied to obtain nanoparticles of steroid hormones. We have managed to obtain a new crystal modification FVII of androgen steroid 3β-hydro-5-androsten-17-one (DHEA), involved in regulation of numerous functions in the human body[5]. The particle size of the drug equals to 102 ± 10 nm. We have also obtained nanoparticles of androgenic steroid 5-androstenediol-3β, 17β, used as a radioprotective and immunostimulating agent, with particle size of 219 ± 9 nm[6]. Advantages and capabilities of the developed cryochemical technology were analyzed. It is stated that it is applicable to a large number of crystalline drug compounds.