PHYSICOCHEMICAL PROPERTIES AND BIOLOGICAL ACTIVITY OF THE NEW ANTIVIRAL SUBSTANCE

Objective: To develop a set of quality control procedures for the promising antiviral pharmaceutical substance L-histidyl-1-adamantylethylamine dihydrochloride monohydrate, a derivative of rimantadine. Methods: Substances and solvents: synthesized in laboratory L-histidyl-1-adamantylethylamine dihydrochloride monohydrate (H-His-Rim•2HCl•H2O), rimantadine hydrochloride (Rim•HCl), 99%, ethanol 96%, N, N-dimethylformamide (DMF) anhydrous, 99.8% and n-hexane anhydrous, 95%, deionized high-resistance water (18.2 MΩ•cm at 25 °C, Milli-Q system), silver nitrate. Infrared (IR) Spectroscopy–Cary 630 Fourier Transform IR Spectrometer, elemental analysis–elemental composition analyzer CHNS-O EuroEA3000, ultraviolet (UV) spectrometry–Cary-60 spectrophotometer, polarimetry–POL-1/2 polarimeter with an external Peltier module, granulometric analysis by optical microscopy (Altami BIO 2 microscope) and low-angle laser light scattering (LALLS)–Master Sizer 3600, measurement of potential for hydrogen–potentiometer PB-11, Spirotox method–the study of temperature dependences of Spirostomum ambiguum lifetime to characterize the biological activity of the studied compounds. Results: The substance H-His-Rim•2HCl•H2O is an amorphous yellowish powder, slightly soluble in water, soluble in ethanol, freely soluble in N, N-dimethylformamide, and practically insoluble in n-hexane. A study of the elemental composition has confirmed the authenticity of H-His-Rim•2HCl•H2O. Comparison of the spectral characteristics of H-His-Rim•2HCl•H2O and Rim•HCl by IR spectroscopy and UV spectrometry confirmed the authenticity of the substance. The racemic form of the substance Rim•HCl with an insignificant amount of impurity of the levorotatory enantiomer was proved polarimetrically: α =-0.0126±0.0003 (1% aqueous solution, 20±0.5 °С). The specific optical rotation of 1% aqueous solution H-His-Rim•2HCl•H2O . In 1% ethanol solution -10.32±0.12. Using the method of laser light diffraction for a substance H-His-Rim•2HCl•H2O, the dimensional spectra «fraction of particles, %-d, μm» were characterized, the maximum of which in hexane is in the region of 40–50 μm. Arrhenius’s kinetics on the Spirotox model established statistically significant differences in ligand-receptor interactions, which are characterized by values of observed apparent activation energy °bsEa, kJ/mol: 132.36±1.55 for H-His-Rim•2HCl•H2O and 176.15±0.48 for Rim•HCl. Conclusion: The developed set of methods for assessment of physical and chemical properties and biological activity of a new antiviral substance H-His-Rim•2HCl•H2O is the basis for establish of regulatory documentation

POLARIMETRIC RESEARCH OF PHARMACEUTICAL SUBSTANCES IN AQUEOUS SOLUTIONS WITH DIFFERENT WATER ISOTOPOLOGUES RATIO

Objective: Methodology development for quality control of optically active pharmaceutical substances based on water isotopologues. Methods: Solutions of L-ascorbic acid, glucose, galactose and valine stereoisomers were prepared using deuterium depleted water (DDW-«light» water, D/H=4 ppm), natural deionized high-ohmic water (BD, D/H=140 ppm), heavy water (99.9% D2O). The optical rotation was observed using an automatic polarimeter Atago POL-1/2. The size distribution of giant heterogeneous clusters (GHC) of water was recorded by low angle laser light scattering (LALLS) method. Results: The infringement of Biot's Law was found for solutions of ascorbic acid, expressed in the absence of a constant value of the specific optical rotation  at a concentration of below 0.1%, depends on the D/H ratio. The inequality was established in absolute values of optical rotation for L-and D-isomers of valine in solutions with different ratios of hydrogen isotopologues. The mutarotation of glucose confirmed the first-order kinetics, and the activation energies were statistically distinguishable for BD and DDW. The mutarotation of the natural galactose D-isomer proceeded with a lower energy consumption compared to the L-isomer. In heavy water, the mutarotation of monosaccharides had different kinetic mechanisms. Polarimetric results correlated with the number and size of GHC, which confirmed the possibility of chiral solvent structures induction by optically active pharmaceutical substances. Conclusion: In the optically active pharmaceutical substances quality control there should be considered the contribution of induced chiral GHC of water to the optical rotation value that depends on the isotopic D/H ratio, the substance nature and the form of its existence at a given pH

New possibility of the latent disease detection in students using the screening method in programme «health»: introduction and efficacy

The new method of the latent chronic disease detection in students using the screening was invented in programme «Health». It was research in students from the different climatogeographic regions for the detection of gastrointestinal disease. The special screening questionnaire designed by us was used in the study. The perceptibility and the diagnostic specificity was studied and estimated. The efficacy of screening use for gastrointestinal disease early diagnostic was ascertained as a result of study. It was marked the significant spread of intestinal dysbacteriosis in students form different climatogeographic regions in adaptation period

Acceleration of the adaptation processes in foreign students with cronic associated viral infection: perspective and possibility (as a result of study in programme «Health»)

The study was research high frequency of chronic associated pathology in the adopted students. These diseases caused delay of adaptation processes, decrease of immunity and increase of morbidity. It was offered the methods of adaptation processes acceleration and morbidity reduction methods in students with chronic pathologic conditions

The satisfaction of patients with chronic dermatoses according to the medical care they received

The article deals with the opinion of patients about different activities of medical organizations. It was established that opinion of patients about the activities of medical organizations depends on many factors, among which the most important were the place of residence, social status, level of education, material security and others.Purpose of the study. To study the satisfaction of patients with chronic dermatoses with the medical care they receive in a metropolis.Materials and methods. The satisfaction of patients with chronic dermatoses with the quality of the services provided in dermatovenerological clinics was studied on the basis of a questionnaire survey of 412 patients living in Moscow. Results. It was established that 74.0% of patients were satisfied with the quality of dermatological care, 19.6% were more likely satisfied than not, 5.8% were more unsatisfied than yes, 0.6% were not satisfied. The attentive and friendly attitude of medical personnel to patients in polyclinic and inpatient departments of specialized medical organizations noted in 91.7% of respondents, inattentive — in 0.6% and found it difficult to answer — 7.7%. The majority of respondents (97.8%) rated the schedule of doctors as convenient and waiting time for a dermatovenerologist's appointment in the clinic is not long (96.8%).The minimum proportion of patients (1.3%) indicated a refusal to conduct the necessary in their opinion examinations and treatment.Conclusion. The majority of patients were satisfied with the specialized care received and practically had no difficulties visiting specialized medical organizations in view of their sufficient number in different areas of the city

Influence isotopic composition of water on combined biological activity adjuvants na2edta and essential trace elements. Message 2

Physico-chemical and biopharmaceutical analysis excipients and drug indicates the absence of the previously announced their inertia. Excipients can exhibit biological activity by themselves, and influence the activity of the active compound. Previously, we have shown that the water depleted in deuterium reduces the toxic effect of disodium ethylenediaminetetraacetate (Na 2EDTA). Disodium edetate is used as a stabilizer in liquid dosage forms including ointments, suppositories and tablets, is known as E386 preservative in the food industry. Zinc is as essential trace elements involved in many vital processes and is a part of the multi-component drugs. We have studied the combined toxicity of adjuvant Na 2EDTA and zinc salts in solutions with different ratios of isotopes of hydrogen (D/H) on biological models Spirotox