Preparation, characterization and studies of physicochemical and biological properties of drugs coating lactose in fluidized beds

Objective: Study physicochemical properties and activity of biotechnological drugs coating lactose particles in fluidized beds for the development of a prospective approach of their identification. Methods: Lactose monohydrate as pharmaceutical excipient; affinity-purified polyclonal rabbit antibodies to recombinant human interferon-gamma as a drug substance; Pilotlab fluid bed apparatus was used for lactose powder saturation with solutions of pharmaceutical substances to the point of granulation (pelletizing); inverse light scattering method (2D-LS) for analysis of micron vibrations frequency spectra of samples surfaces for light intensity distribution in time by values of d1, d2, d3 primary descriptors; low angel and dynamic laser light scattering (LALLS, DLS) methods for distribution of lactose-water (LW) supramolecular complexes into volume fractions (micron "size spectra"), using the Master Sizer 2000 instrument and Zeta Sizer Nano ZS instrument in the nanoscale; Spirotox method for research of biological activity to determine the activation energy (Ea) values of cell death in solutions of tested samples. Results: Changes in 2D-LS scattering time on sample surfaces, described by topological descriptors, made it possible to clearly differentiate the intact lactose from fluidized samples by specific corridors in coordinates di=F(t). The calculated activation energy (Ea) values of cell biosensor death process in solutions of drugs coating lactose allow to characterize the biological activity of it in the initial (by Ea increase) and activated state (by Ea decrease) after the creation of intra-laboratory transmucosal conditions. A unique dimensional spectrum of LW complexes in the nanoscale range was obtained by DLS. The differences between samples in the distribution of LW complexes in the size range from 1 µm to 125 µm was showed by LALLS. Conclusion: The developed approach, including Сhemometrics, laser and biotesting methods can be used for qualitative the analysis tasks as well as for analytical control of the fluidization process in cases where identifiable pharmaceutical substances are not distinguishable by traditional analytical methods. © 2020 The Authors

Лекарственные препараты на основе релиз-активных антител

A number of the released-active drugs with proved safety and efficacy against viral infections, cough, stress and anxiety, brain circulation impairments, metabolic disorders, etc., exist in the pharmaceutical market for more than 15 years. Results of the preclinical studies have revealed some of the aspects of the released-active antibodies action. Nevertheless, the exact mechanism of each drug's action is still a subject of research. The aim of the present review is to investigate the physical-chemical principles of mechanism of action of the released-active drugs.Более 15 лет на фармацевтическом рынке представлена группа релиз-активных препаратов с доказанной эффективностью и безопасностью в лечении вирусных инфекций, кашля, стресса и тревоги, нарушений мозгового кровообращения, расстройств метаболизма и др. Результаты доклинических исследований позволили получить представление о некоторых аспектах действия антител в релиз-активной форме. Тем не менее точный механизм развития эффектов каждого препарата остается предметом изучения. Цель настоящего обзора - рассмотреть физико-химические основы механизма действия релиз-активных препаратов

Лекарственные препараты на основе релиз-активных антител

A number of the released-active drugs with proved safety and efficacy against viral infections, cough, stress and anxiety, brain circulation impairments, metabolic disorders, etc., exist in the pharmaceutical market for more than 15 years. Results of the preclinical studies have revealed some of the aspects of the released-active antibodies action. Nevertheless, the exact mechanism of each drug's action is still a subject of research. The aim of the present review is to investigate the physical-chemical principles of mechanism of action of the released-active drugs.Более 15 лет на фармацевтическом рынке представлена группа релиз-активных препаратов с доказанной эффективностью и безопасностью в лечении вирусных инфекций, кашля, стресса и тревоги, нарушений мозгового кровообращения, расстройств метаболизма и др. Результаты доклинических исследований позволили получить представление о некоторых аспектах действия антител в релиз-активной форме. Тем не менее точный механизм развития эффектов каждого препарата остается предметом изучения. Цель настоящего обзора - рассмотреть физико-химические основы механизма действия релиз-активных препаратов

The new two-dimensional light scattering method for recognition of pharmaceutical enantiomers

The results of applying the developed mathematical model of the folding of two-dimensional light scattering (2D-LS) patterns into a descriptor to identify the enantiomers of optically active pharmaceutical substances are presented in the article. The following pharmaceutical substances were a subject of this research: L-valine, D-valine, racemic mixture L, D-valine, L-glucose, D-glucose, and L-ascorbic acid. A digital microscope with high spectral density was used to obtain instant 2D-LS patterns. The obtained data were mathematically processed using the original computer program “Vidan”, which uses a mathematical model for the folding of the 2D-LS pattern into descriptors, which are analogs of topological indices in quantitative structure-activity correlations approaches to drug analysis. The 10 descriptors were used as criteria for the difference in the 2D distribution of the scattered light intensity. The use of mono- and multidescriptor analyses allowed us to determine the authenticity of pharmaceutical substances of different classes and their optical isomers. It was found that the dispersion of crystalline substances of optical antipodes up to submicron size led to the leveling of light scattering patterns. The mathematical model was developed and applied for the folding of 2D-LS diagrams into a descriptor. This allowed us to identify the optical antipodes of pharmaceutical substances. © 2020. All rights reserved

Possible Mechanisms of Relations between the Thermal Neutrons Field and Biosphere

This paper proposes some results concerning the interaction of living matter of different organization levels (prokaryotes and eukaryotes) with the flux of thermal neutrons. The phenomenon of the virtual neutron trap was tested during the passage of thermalized neutrons from the Pu-Be couple through a flat layer of E. coli suspension. We have studied the metabolic characteristics of A. salina cysts before and after artificial neutron flux exposure. It has been demonstrated that the concentrations of some metals in samples of alive and dead cysts irradiated with an artificial flow of thermal neutrons are not equal. The content of Mn in alive A. salina samples has increased more than ten-fold after their interaction with neutron flux, while the amount of As decreased by a factor of two after exposure. Levels of other elements (Al, Cr, Ni, Cu, Cd, and Pb) did not show any significant difference. Trace element composition of cysts was assessed using the method of atomic absorption spectroscopy with electrothermal atomization and the Zeeman background correction. © 2020 Anton V. Syroeshkin et al

Deuterium as a tool for changing the properties of pharmaceutical substances (Review)

The review is devoted to the influence of the hydrogen isotope–deuterium on biological models of organisms and the biological activity of pharmaceutical substances. The positions of the influence of deuterium on the properties of active pharmaceutical ingredients and excipients are examined from different perspectives. The first position reflects an increase in the kinetic isotope effect (KIE) in processes involving known pharmaceutical substances in aqueous solutions with a deuterium/protium ratio (D/H) below natural. For the first time, the dose-response diagram shows the identity of deuterium with essential trace elements, when a deficiency and excess of an element reduces the organism's vitality. Improved kinetic characteristics are demonstrated for the molecular and organism levels of different hierarchical gradations. In particular, they consist in the possibility of increasing the dissolution rate of substances by influencing the carbohydrate mutarotation processes and the optical activity of chiral substances, increased accumulation of essential elements in medicinal plants and other processes associated with a possible change in metabolic pathways in the cell and the organism as a whole. The second considered position of the influence of deuterium is associated with the use of deuterated substances–new compounds or obtained by substitution of protium in known protium analogues. The KIE is presented, which is expressed in a decrease in the biotransformation rate as a result of deuteration, it allows predicting a rapid development of the new direction in the development of drugs. Having an identical therapeutic effect, deuterated analogs provide improved pharmacokinetic characteristics, such as reduced toxicity, blocked epimerization of optically active substances, and a change in the mechanisms of biotransformation. The obtained results make it possible to predict the mechanisms of the effect of deuterium on the biochemical transformations of pharmaceutical substances in the organism. © 2021 The Authors. Published by Innovare Academic Sciences Pvt Ltd

МЕТОД ДВУМЕРНОГО ДИНАМИЧЕСКОГО СВЕТОРАССЕЯНИЯ ДЛЯ ОПРЕДЕЛЕНИЯ ПОДЛИННОСТИ МАТЕРИАЛОВ И ЛЕКАРСТВЕННЫХ СРЕДСТВ

A method of two-dimensional dynamic backscattering (2D-DLS) with data processing according to a mathematical model of topological descriptors is proposed. The set of topological descriptors makes it possible to fingerprint of the surface, which is in one-to-one correspondence with the chemical composition and the method of its preparation. The 2D-DLS method was introduced at a pharmaceutical enterprise to control powdered medicinal substances obtained in fluidized bed chambers, as well as at two plants for the production of water with a modified isotopic composition for operational control of drugs in terms of the performance of distillation columns in terms of "authenticity".Предложен метод двумерного динамического обратного светорассеяния (2D-DLS) с обработкой данных по математической модели топологических дескрипторов. Метод основан на изменении топологии светорассеяния от поверхности при низкочастотном колебаниях супрамолекулярных комплексов. Набор дескрипторов позволяет формировать фингерпринт поверхности, находящийся во взаимно-однозначном соответствии с химическим составом и способом его приготовления. Метод 2D-DLS внедрен на фармацевтическом предприятии для контроля порошкообразных лекарственных веществ, получаемых в камерах псевдоожиженного слоя, а также на двух заводах по производству воды с измененным изотопным составом для оперативного контроля препаратов