POLARIMETRY AND DYNAMIC LIGHT SCATTERING IN QUALITY CONTROL OF CARDIOTONIC AND HYPOTENSIVE TINCTURES

Objective: To substantiate the possibility of using polarimetry to control the quality of tinctures as an additional pharmacopoeial method. Methods: The polarimetric method (POL-1/2, Atago, Japan, the measurement accuracy of±0.002 °) was used to measure the optical activity (α °) of motherwort, valerian and hawthorn tinctures. The dynamic light scattering method (DLS; Zetasizer Nano ZS, Malvern, UK) was used to assess the stability of alcoholic and aqueous dilutions of tinctures according to the intensity of dynamic light scattering dependent on the size (d, nm) of the dispersed phase particles and the values of the electrokinetic potential (ξ, mV). Results: For the first time in this investigation, the polarimetry approach was proposed to evaluate the cardiotonic and hypotensive tinctures' quality and for their identification. Valerian tincture, dilution 1:40,-0.10°<α°<-0.89°; motherwort, tincture-dilution 1:10,-0.10°<α°<-2.21°; hawthorn, tincture without dilution,-0.76°<α°<-1.55°-these are the acceptable ranges of optical activity (α°) of their alcohol dilutions. Beyond these intervals, the use of the polarimetric approach is impossible. Values of optical activity below 0.1 correspond to too low a content of optically active components. Tinctures with optical activity above the upper value of the interval were unstable dispersed systems with low values of the electrokinetic potential (|ξ|≪25mV) and micron particle sizes. Reference tinctures were made from raw materials (Leonurus cardiaca L.) to verify the results. The quality parameters: optical activity (α°), spectra of dynamic light scattering by intensity, volume, and number ("I-d"; "V-d"; "N-d"), electrokinetic potential (ξ) values, and photon pulse count per second (Count Rate, kcps) corresponded to the results obtained for pharmaceutical dosage forms. Conclusion: The permissible intervals of optical activity (α°) of their ethanol dilutions, as well as their relationships with the particle size of the dispersed phase and the values of the electrokinetic potential, were established for the first time to evaluate the quality of tinctures. The obtained results show that polarimetry can be recommended as an additional pharmacopoeial quality control method for tinctures

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

APPLICATION OF MATHEMATICAL MODELING AND PHYSICO-CHEMICAL ANALYSIS METHODS IN THE PREDICTION OF BIOLOGICAL ACTIVITY AND QUALITY CONTROL OF GOSSYPOL DERIVATIVES

Objective: The purpose of this work was to evaluate in silico biological activity profiles of real and virtual molecular structures of gossypol derivatives and to develop methods of Physico-chemical analysis to control their quality. Methods: Substance of gossypol-acetic acid (GAA) and 14 virtual derivatives; PASS and ChemicDescript QSAR methods; low angle and dynamic laser light scattering (LALLS, DLS) methods; IR Spectroscopy–Cary 630 Fourier Transform IR Spectrometer, UV spectrometry–Cary-60 spectrophotometer, Optical microscopy (Altami BIO 2 microscope); Spirotox method for a sample’s biological activity. Results: A distance-based topological Balaban index (J) was successfully selected by ChemicDescript analysis; the Pa meaning by PASS Online program showed maximum (from 0.8 to 0.9) variations of antitumor and antiandrogenic and minimum of antiviral activities of GAA derivatives (Pa<0.5) despite the existing literature data. Microscopy and DLS methods demonstrated the values of high powder dispersion d=0.8 nm and weak stability of colloidal particles =-0.9 mV. According to UV data =42.4±0.8 (100 ml·g-1·cm-1) at λmax=380 nm. The LALLS method determined the GAA dissolution rate constant in ethanol: k=0.041±0.004 s-1. The calculated activation energy values of cell biosensor death process in 1 mmol solution of GAA in N,N-DMF: °bsEa=174.36±0.45 kJ·mol-1 in comparison with the solvent medium: °bsEa=213±1.55 kJ·mol-1 Conclusion: The developed approach of chemometric, laser and biotesting methods can be used for the identification of biologically active properties, as well as for qualitative analysis within the development of the standard for the pharmaceutical substance of natural polyphenols

Chelation of Zinc with Biogenic Amino Acids: Description of Properties Using Balaban Index, Assessment of Biological Activity on Spirostomum Ambiguum Cellular Biosensor, Influence on Biofilms and Direct Antibacterial Action

The complexation of biogenic molecules with metals is the widespread strategy in screening for new pharmaceuticals with improved therapeutic and physicochemical properties. This paper demonstrates the possibility of using simple QSAR modeling based on topological descriptors for chelates study. The presence of a relationship between the structure (J) and lipophilic properties (logP) of zinc complexes with amino acids, where two molecules coordinate the central atom through carboxyl oxygen and amino group nitrogen, and thus form a double ring structure, was predicted. Using a cellular biosensor model for Gly, Ala, Met, Val, Phe and their complexes Zn(AA)2, we experimentally confirmed the existence of a direct relationship between logP and biological activity (Ea). The results obtained using topological analysis, Spirotox method and microbiological testing allowed us to assume and prove that the chelate complex of zinc with methionine has the highest activity of inhibiting bacterial biofilms, while in aqueous solutions it does not reveal direct antibacterial effect

Express method for particle size analysis in solid, liquid, and amorphous materials using 3D calibration curve and 2D-DLS dynamic light scattering

This study proposes a new method for particle size studying based on the use of topological descriptors for various media and types of matter. The sizes of supramolecular particles in water-lactose complexes were studied using the diffuse dynamic light scattering (DLS) method. Mist-Standart latex balls were used to generate a 3D calibration curve, followed by empirical particle size determination. In order to confirm the output, the resulting sizes were compared for a number of silver proteinate solutions, preliminary analyzed by laser light scattering (using ZetaSizer equipment by Malvern Instruments Ltd, UK). The new method uses a simplified procedure, provides a quick solution and may be used for both quality control of cloudy and opaque medicinal substances and excipients as well as in other fields of nanotechnology. Keywords: nanoparticles, particle size, silver proteinate, latex nanoparticles, dynamic light scatterin

Development of an effective way to increase the biological activity of nicotinamide – a new strategy to protect against photoageing and skin neoplasia

The objective of this work is to demonstrate changes in properties and increase of biological activity of nicotinamide (NAM) substance for skin protectants activated by mechanical activation (MA). To assess the physical, chemical and biological properties of NAM were used biotesting by the Spirotox-method, direct and indirect optical methods (microscopy, laser diffraction), infrared spectroscopy, pH-metry. The results of the study showed an increase in biological activity, expressed in changes in the energy of activation of cell transition to the “dead cell” state on the example of biosensor Spirostomum ambiguum. Also we indicated an increase in the rate of the chemical process of dissolution of mechanoactivated molecular crystals of nicotinamide (NAM) expressed in the values of the first order rate constant. Mechanical activation at a high rate of NAM substance powder deformation has led to changes in physical, chemical and biological properties of the drug, which can be used in medicine to increase efficiency and reduce doses of pharmacotherapy

PHYSICAL AND CHEMICAL CHARACTERISTICS OF AQUEOUS COLLOIDAL INFUSIONS OF MEDICINAL PLANTS CONTAINING HUMIC ACIDS

Objective: Study of physical and chemical activity of biologically active substances containing humic complexes (HCs). Comparison of various preparations available on the market. Development of a modern express method of quality control. Methods: Preparations containing HCs manufactured by Biotechnology System, BIODORON, Faberlic, etc. Built-in flux density sensor TES-92 (TES Electrical Electronic Corp., Taipei, Taiwan), which was used to determine the flux density of radio thermal emission in the gigahertz range. Zetasizer Nano ZSP (Malvern Panalytical, Worcestershire, UK) was used to determine the size of nanoparticles in preparations containing the HCs and MP with humic acids (HAs). Results: In the course of experiments for studying the intrinsic radio thermal emission of HAs preparations, differences were found between HAs from different manufacturers, for example, HAs produced by Biotechnology System with a flux density of 35 ± 5 µW/m2 at 37°C differs several times from similar preparations produced by other companies. When diluting HAs from Biotechnology System 10, 100 and 1000 times, the emissivity of the preparations is preserved. Also, with the expiration of the 2-year shelf life of the preparation, as stated by the manufacturer, a sharp drop in emissivity of 20 times is observed. Conclusion: The radio thermal activity of HAs preparations revealed during the experiments allows developing a method that can be utilized to control the quality of manufactured products, as well as control the expiration dates of preparations without opening the primary package

Mitochondrial activity of cancer and normal mesenchymal stem cells

We showed that cancer and normal mesenchymal stem/stromal (MSC) cells in vitro in a deuterated growth medium show a decrease of mitochondrial activity (MA), while in a deuterium-depleted medium an increase. This was established using mitotracker and rhodamine 123, and was also confirmed by expression of the UCP1 gene. The correlation dependence of mitochondrial activity in a medium with a changed ratio of deuterium/protium (D/H) and supramolecular structures was established, using the laser diffraction method. Density inhomogeneities in the deuterated medium are noted to be large, and in the deuterium-depleted medium small, in comparison with the control