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Introduction. The Laboratory of Drug Formulation Development at the N. N. National Medical Research Center of Oncology developed a liposomal dosage form of FS tetra-3-phenylthio-pthalocyanine hydroxyluminide (TPHA) for which a simple, accurate and easily reproducible method of quantitative determination of the main active substance and excipients in the drug product was needed. High-performance thin-layer chromatography (HPTLC) was chosen as such a technique.Aim. The aim of this work was to develop chromatographic methods for the quantitative determination of excipients in a liposomal dosage form of a tetra-3-phenylthiophthalocyanine hydroxyaluminium (TPHA).Materials and methods. Determination of substances was carried out by the method of high-performance thin-layer chromatography (HPTLC) followed by TLC-densitometry. Substance TPHA 98 % (Federal State Unitary Enterprise "SSC "NIOPIK", Russia), placebo lyophilized liposomal form without TFHA in the composition (FSBI "National Medical Research Center of Oncology. N. N. Blokhin" of the Ministry of Health of Russia), egg phosphatidylcholine (96 %, CAS № 97281-44-2, EPC Lipoid, Germany), cholesterol (≥99 %, CAS № C8667, Sigma-Aldrich, Japan), sucrose analytical grade (CHIMMED, Russia) and various organic solvents.Results and discussion. The selected mobile phase for HPTLC analysis: isopropanol: ammonia 25 % aqueous 80 : 20, separation time was 20– 25 min (l = 75mm), t = 20 °С. To visualize the spots of sucrose, phosphatidylcholine, and cholesterol, a 5 % solution of phosphomolybdic acid was chosen. The stability of the standard samples was confirmed on a series of prevalidation studies. Validation of the methodology was carried out.Conclusion. For quantitative determination of sucrose, phosphatidylcholine and cholesterol in a new liposomal dosage form, the method of HPTLC with TLC-densitometry was chosen, which allows identifying all three components in the dosage form simultaneously. The method was validated.

Introduction. LHS-1269 is an indolocarbazole derivative with high antitumor activity. Due to the hydrophobic properties of the active substance, the use of organic co-solvents – dimethyl sulfoxide (DMSO) and ethanol – is required to obtain an injectable dosage form (DP). However, the inclusion of organic solvents in the composition of the DF carries a potential risk of side effects as a result of the use of the drug.Aim. Selection of auxiliary substances for obtaining an aqueous solution of hydrophobic indolecarbazole derivative, which allows minimizing the concentration of organic solvents in the composition of DF.Materials and methods. The object of the study is the active substance LHS-1269 series 010320, produced in the Chemical Synthesis Laboratory of the N. N. Blokhin National Medical Research Center of Oncology. The following auxiliary substances were used to obtain model compositions: Kollidon® 17 PF, Kollisolv® PEG-400, Kolliphor® P 188, Montanox™ 20, DMSO (p.a.), ethanol 95 % (standardized according to pharmacopoeia quality standard ФС.2.2.0019.18 of The State Pharmacopoeia of the Russian Federation). Analytical scales OHAUS Analytical Plus AP 100S and laboratory scales AND DL-120 were used for weighing LHS-1269 and auxiliary substances. The dissolution and mixing of the components was carried out on an IKA® C-MAG HS 4 magnetic stirrer.Results and discussion. In the course of the study, 2 groups of model compositions were obtained and estimated, comprising a complex of two or more auxiliary substances as a solubilizer. The first group of formulations contained DMSO at a concentration of 5 % and ethanol at concentrations from 0 to 15 %. The compositions of the second group included DMSO from 0 to 4 %. As a result, it was found that the addition of 5 % Kolliphor® P 188 to the composition of the solution reduces the content of ethanol to 5 %. In this case, with further decrease in ethanol, turbidity of the solution and precipitation are observed. Reducing the concentration of DMSO in the DF to 2 % was achieved by using a combination of 20 % ethanol and solubilizer complex – Kollidon® 17 (20 %), Kollisolv® PEG-400 (20 %) and Kolliphor® P 188 (5 %). In this case, the total dissolution of the active substance without DMSO was observed when compensating for the organic solvent by introducing additional auxiliary substances – Montanox™ 20 (5 %) and benzene (2 %).Conclusion. As a result of the research, the compositions of the auxiliary substances of solubilizers are selected, allowing to obtain an aqueous solution of the hydrophobic compound LHS-1269 with a minimum concentration of organic solvents.

Background. A glycoside derivative of indolocarbazole LHS-1269, one of the new drugs selectively affecting tumors, which was first synthesized at the N.N. Blokhin National Medical-Research Center of Oncology of the Ministry of Health of Russia, is of particular scientific interest. Experimental studies demonstrated a multi-target mechanism of action of this compound. LHS-1269 interacts with several intracellular targets and induces various pathways of cell death. Several innovative models of the dosage forms were designed to achieve the highest antitumor activity of the compound and to perform further preclinical studies.Aim. To develop the methods for the quantitative determination of LHS-1269 in pharmaceutical compositions proposed as a result of the search for the optimal dosage form.Materials and methods. The study analyzed the spectrophotometric characteristics of LHS-1269 solutions in dimethylformamide, dimethylsulfoxide (DMSO) and in the mixture of solvents DMSO–ethyl alcohol, as well as electronic absorption spectra of the excipients in the mixture of solvents DMSO–ethyl alcohol. Spectrophotometric measurements were performed on a Cary 100 spectrophotometer (Varian, Inc., Australia) in the wavelength range from 200 to 500 nm. The standard sample is the substance LHS-1269 (N.N. Blokhin Oncology Research Center of the Ministry of Health of Russia).Results. The carried out studies showed that LHS-1269 solutions in dimethylformamide, DMSO and mixture of DMSO– ethyl alcohol are suitable for spectrophotometric measurements. Several variants of the methodology for the assay of LHS-1269 in various dosage form models that differ in the content of the active substance and the excipients composition have been developed: LHS-1269 concentrate for solution for injection and infusion; lyophilisate for solution for injection; liposomal lyophilisate for dispersion for injection.Conclusion. Techniques for the assay of LHS-1269 in dosage form models have been developed. It has been shown that the developed techniques are applicable for LHS-1269 quantitative determination in innovative dosage forms containing polymeric low molecular weightsolubilizers, lipids, cholesterol, mono- or oligosaccharides as excipients.

The objective: exploring the frequency of circulation of genotypes and alleles of rs2227983 polymorphism of EGFR gene among patients with allergic bronchial asthma with various levels of control.Subjects and Methods. The study includes adult individuals (n = 396) divided into two groups: Group 1 (main) – individuals with allergic bronchial asthma (ABA), Group 2 is a control one. ABA Group consisted of 179individuals (118 women и 61 men) aged 37.4 ± 14.2 years. Control Group consisted of 217 individuals (110 women и 107 men) aged 30.0±9.1years. All subject included in ABA Group and Control Group underwent molecular genetic tests for rs2227983 polymorphism of EGFR gene using polymerase chain reaction.Results. The comparison of distribution of gene EGFR genotypes showed statistically significant predominance of genotype AGcarriers in the group of patients with ABA (48.6%), versus Control Group (36.9%); p < 0.05. Besides that, there is a predominance of number of carriers of heterozygote genotype АG of EGFR gene among patients with ABA (57.7%) with a controlled course of the disease versus Control Group (36.9%); p < 0.05. Also, it has been found out that rs2227983 genotype of EGFR gene was more frequent in women with controlled ABA (67.4%) compared to women from Control Group (32.7%); p < 0.05.Conclusion. The results of the conducted study allowed analyzing the connection of single nucleotide rs2227983 polymorphism ofEGFR gene with ABA including various levels of control of the course of the disease. Genotype АG of single nucleotide polymorphism rs2227983 of EGFR gene increases the risk of developing ABA. Alongside this, АG genotype of EGFR gene is correlated with the controlled course of ABA.

Liposomes are one of the most well-known and promising nanoscale drug delivery systems. Liposomal medicinal products are successfully used in clinical practice for cardiovascular, oncological, dermatological, and other indications. The development of liposomes and their widespread implementation in clinical practice are relevant tasks.The aim of the study was to summarise and analyse scientific data regarding the structure, composition, and classification of liposomes, as well as specific aspects of liposome production methods.This review covers up-to-date information on marketed liposomal medicinal products. The authors illustrate how production methods affect the composition and structure of liposomes. The size and lamellarity are important characteristics of liposomes that determine the encapsulation efficiency and biodistribution of active pharmaceutical ingredients (APIs). The choice of excipients depends on the intended use of liposomal medicinal products. The article summarises the main liposome production methods, highlighting specific usage aspects, advantages and disadvantages. Conventional liposome production methods are easy to apply and do not require complex equipment, and their principal disadvantages include the low efficiency of API encapsulation within liposomes and the high complexity of scaling up technological processes. The authors pay special attention to microfluidic techniques for liposome preparation, which are characterised by a highly controlled technological process (in terms of size distribution and lamellarity), high reproducibility, and scalability to the level of industrial production and are applicable to encapsulating different APIs.

The possibility of anionic synthetic surfactants removal from petrochemical enterprises wastewater using waste of thermal power plants (carbonate sludge) as a sorption material has been investigated. The efficiency of carbonate sludge for the sorption of anionic synthetic surfactants has been established. The use of an adsorption plant (with carbonate sludge as a sorbent) for the wastewater treatment from anionic synthetic surfactants at treatment facilities of enterprises will make it possible to carry out biological wastewater treatment more efficiently, reduce the costs of wastewater neutralization and reduce the anthropogenic load on water reservoirs.

Objective: Development of a lyophilized injectable dosage form LCS-1208, an original antitumor drug based on an indolocarbazole derivative. Methods: The prepared solution of the injectable dosage form LCS-1208 is transferred to sterilizing filtration, which is carried out under vacuum on a «Stericup» filter unit with a filter pore size of 0.22 μm. The sterile solution of the injectable dosage form LCS-1208 is poured into sterile vials using a dispenser and lyophilized in a freeze-drying chamber. At the end of drying, the preparation is corked in the chamber of a sublimation unit using a hydraulic device and transferred to crimping with aluminum caps using a seaming machine. Quantitative determination of the drug content was determined by spectrophotometry using a standard sample at λ = 320±2 nm. The pH was determined by potentiometry. Results: A freeze-drying regimen for the injectable dosage form LCS-1208 has been developed. The required solution freezing temperature was established taking into account the presence of 2 eutectic zones: a solution of LCS-1208 in DMSO (-35 ÷-32) °С, an aqueous solution of Kollidon 17PF (-10 ÷-8) °С. As a result of a series of experiments, the optimal lyophilization regime was chosen that does not require preliminary freezing in a low-temperature chamber, with freezing on the shelves of freeze-drying at a temperature of-47 °C without their preliminary cooling. The most acceptable vial filling volume was determined, amounting to 3 ml, and the rate of temperature rise during secondary drying of the preparation was justified. When using the developed regime of lyophilization of the LCS-1208 solution, it was shown that it can be sublimated while preserving the initial qualitative and quantitative characteristics. Conclusion: In this article, using the example of creating a lyophilized injectable dosage form LCS-1208 (the original antitumor drug from the indolocarbazole group), the main problems that arose during the lyophilization of the selected composition of the model solution, as well as ways to improve the process.

This study reports the characteristics of atmosphere corrosivity parameters on the sea coasts of Russia, namely, on the Arctic and Pacific Oceans and the Black Sea. It gives the results of predicti...

Abstract— The work is aimed at the synthesis and analysis from NS4A of hepatitis C virus (HCV) antigen peptide fragment that contains a conserved B-cell and T-helper epitopes. The 24-mer peptide VIVGRIILSGRPAVIPDREVLYRK-NH2, which contains the main immunogenic site 24–46 of HCV NS4A antigen (corresponding to the 1681–1703 amino acid residues of the HCV polypeptide), subtype 1b, has been prepared via solid-phase synthesis according to the Fmoc-protocol. Particles with diameters of 73 ± 10 nm (30%) and 236 ± 5 nm (70%) have been detected in the water solution of the highly purified peptide (0.5 mg/mL) by dynamic light scattering. The polydispersity index of 0.377 ± 0.012 implies the existence of heterogeneity because of the aggregation of the peptide molecules. The ζ-potential of the peptide aggregates has been determined as 7.0 ± 0.5 mV by means of electrophoretic light scattering. These data confirm the possibility for the development of a nanoscale liposome form of the peptide preparation. Immunoreactivity of the synthesized highly purified peptide has been studied with the use of blood sera of patients with chronic hepatitis C. Antipeptide immunoglobulins G have been detected in 41.7% of serum samples. Thus, this peptide has been shown to reproduce at least one B-epitope, to which antibodies are raised during natural HCV infection. The synthesized 24-mer peptide is a promising candidate for further research and for use as a potential immunogen for the design of a nanoscale therapeutic immunogenic liposomal peptide composition with synthetic lipids as an adjuvant.

Chronic viral hepatitis C (CHC) is a ubiquitous infectious disease, a significant limitation of which WHO attributes to the use of a new highly effective antiviral therapy. Previously, two B-cell epitopes were identified in NS4a antigen of the hepatitis C virus (HCV). It was shown that certain titers of antibodies (ABs) to the extended C-terminal epitope (1687-1718 a.a.) can predict a high probability of achieving a sustained virological response (SVR) to standard therapy with pegylated interferon-α and ribavirin.The aim of the work was to determine immunoreactivity of two B-cell epitopes (middle and C-terminal) of NS4a antigen, and to estimate a possible association of ABs to them with the achievement of SVR after standard interferon therapy and treatment with direct antiviral drugs (DAAs) daclatasvir and sofosbuvir (velpanat).Blood serum samples of patients with CHC (n = 113), of which 55 participants received standard interferon therapy, 50 received velpanate treatment, the remaining 8 received no therapy were examined. The middle B-cell epitope (positions 24-34 a.a.) of NS4a was synthesized by the solid-phase method, while the C-terminal epitope (34-54 a.a.) was obtained using genetically engineered techniques. Enzyme immunoassay (ELISA) testing of the sera collected before treatment was performed for the two selected epitopes according to the conventional methods.The antibodies to the C-terminal epitope were detected significantly more frequently than those to the middle one (p = 0.01) when analyzing the blood sera of patients (n = 113). The presence of ABs to the C-terminal epitope in the serum samples of participants who completed standard interferon therapy was associated with the achievement of SVR (p = 0.0245). In the blood sera of participants who completed therapy with velpanate, an association of the presence of ABs to the C-terminal epitope with the achievement of SVR was also established (plt; 0.0001). The presence of ABs to the middle B epitope was not associated with the achievement of SVR, regardless of the therapy used.The observed difference in the immunoreactivity of the two B-cell determinants may be associated with the localization of the nearest Th-epitopes, the sensitivity of NS4a antigen to proteolytic enzymes, and the peculiarities of epitope presentation by antigen-presenting cells. However, it should be noted that the immunoreactivity of the middle B-epitope is poorly studied. Although the association of ABs to the C-terminal epitope with the achievement of SVR has been shown by several scientific teams, the detailed molecular mechanism of their influence on the effectiveness of therapy is unclear.In CHC, ABs to the C-terminal epitope of NS4a are produced more frequently than those to the median epitope. The presence of ABs to the C-terminal epitope is a predictive marker of a high probability of achieving SVR, regardless of the type of therapy and antibody titer.

It is proposed to purify gas emissions from industrial enterprises to remove sulfur dioxide by the adsorption method using pelletized sorption material based on energy waste — chemical water treatment sludge of heat-and-power plants, which is formed at the stage of pre-treatment of natural water during liming and coagulation. The characteristics of the adsorber loaded with the obtained material for cleaning gas emissions to remove SO2 are calculated. It is proposed to modernize the existing technological scheme for purifying gas emissions of the sodium bisulfite production line at JSC “Chemical plant named after L. Y. Karpov.” Calculations describing the economic and environmental effect of the new technological scheme for cleaning gas emissions to remove sulfur dioxide are presented.

The results of predictions concerning the long-term corrosion losses of structural metals in the continental territory of Russia with rural atmospheres and in certain locations with urban atmospher...

The necessity of studying organic waste as a secondary energy resource for a waste-heat boiler with further use of the resulting ash for the adsorption of heavy metal ions is shown. The adsorptive purification of waste water from copper ions by ash of organic waste is considered. The chemical composition and technological characteristics of organic biomass, the characteristics of the boiler and the toxicity of the resulting ash have been determined. The chemical composition of the ash was obtained. The isotherm of adsorption in static conditions and the output curve of adsorption in dynamic conditions of copper cations by ash of organic waste were constructed. The process of wastewater treatment of galvanic production is presented. It is concluded that the use of the adsorption method allows for a high degree of wastewater purification and its possible reuse for the technological needs of the enterprise.

Atrial fibrillation (AF) is one of the most common and dangerous heart rhythm disorders. Lone AF is due to a genetic predisposition. Foreign studies have proven the association of rs2200733 polymorphism of chromosome 4q25 with AF. No such studies have been conducted in the Russian Federation. Purpose of the study: to determine the association of the rs2200733 polymorphism of chromosome 4q25 with the development of AF, and to exclude the possible connection of the studied polymorphic marker with concomitant cardiovascular pathology. A total of 247 patients with AF were examined (113 from lone AF, 134 from secondary). Control group - 182 healthy people. Behavior: ECG, EchoCG, Holter ECG monitoring, blood test for thyroid hormones, VEM, CAG, molecular genetic research. In the group of patients with AF, the TT genotype was detected in 12.95%, which is statistically significant more often than in the control group (4.94%), p0.05). In patients with the TT genotype, the mean LA size was 3.738 ± 0.494 cm, it was statistically significantly smaller than in patients with the CC genotype, which corresponded to 3.925 ± 0.629 cm, p

To predict $$K_{1}^{{{\text{pr}}}}$$ values, the dose-response functions (DRFs) presented in the ISO 9223:2012(E) standard were used, both new and universal ones. This work is based on experimental data of the corrosion losses of St3, Zn, Cu, and Al for the first year of exposure ( $$K_{1}^{{\exp }}$$ ) and calculated by the DRF values ​​of corrosion losses for the first year ( $$K_{1}^{{{\text{pr}}}}$$ ) for the test sites conducted in the framework of international UN/ECE and Russian programs, as well as the MICAT project. For these places, the necessary atmospheric aggressiveness parameters for DRF were taken into account. The categories of atmospheric corrosion activity are adopted in accordance with ISO 9223:2012(E) standard.

Aim. The aim of this work was to create a lyophilized liposomal dosage form of native hydrophobic antitumor compound from the group of indolocarbazole derivatives — LHS-1208. Materials and methods. Quantitative determination of the drug content was carried out on a Cary 100 spectrophotometer using a standard sample at λ = 320 ± 2 nm. The analysis of the average diameter of liposomes was carried out by the method of correlation spectroscopy of light scattering using devices Nicomp-380 nanosizer and Zetasizer Nano ZS zetasizer, using the latter, the zeta potential of the liposomal dispersion was also measured. To measure the pH of the solution, a HANNA pH 211 pH meter was used. The dynamic viscosity was measured on a Vibro Viscometer SV-10 viscometer. Lyophilization was carried out in an Edwards Minifast DO.2 freeze-drying chamber. Results. Experimental models of compositions of lyophilized liposomal dosage form LHS-1208 with various molar ratios of components were obtained and analyzed. TLC analysis using several solvent systems can be used to detect and identify LHS-1208 in a liposomal dosage form. According to the results of the study, a spectrophotometric method was developed for the quantitative determination of the LHS-1208 content in the composition of a liposomal dosage form. Based on the studies carried out, quality indicators were selected for standardization of lyophilized liposomal dosage form LHS-1208 and subsequent development of the draft regulatory documentation. Conclusion. As a result of the complex pharmaceutical research, the optimum composition of the components was determined, and the technology for production of liposomal dosage form LHS-1208 was developed.

A technology for adsorption treatment of a TPP’s wastewater from oil films and dissolved oil products by developed powdery and granular sorption materials based on carbonate sludge is proposed. Carbonate sludge is an energy waste generated during the preliminary purification of raw water during liming and coagulation. The technological characteristics and the adsorption capacity of the sludge with respect to dissolved and emulsified oil products are determined. To increase the adsorption capacity and wettability by nonpolar compounds, it is proposed to carry out volumetric hydrophobization of carbonate sludge with Silor silicone fluid. Powdered material was obtained by modifying sludge (humidity 3%, particle size dh = 0.01–0.05 mm) with 100% Silor liquid with a volume ratio of solid and liquid phase of 5 : 1 followed by heat treatment at 150°C for 60 min until a constant mass was established. The oil capacity of the material of 0.95 g/g, the contact angle of 115°, and the technological characteristics of the sorption material were determined. For TPPs’ wastewater treatment from oil products, it is proposed to use the material for collecting floating oil films in the sumps of the technological scheme. A technology has been developed for producing granular sorption material: granules formed from carbonate sludge when mixed in a ratio of 1 : 2 with a binder liquid sodium glass are heat treated at 700°C for 60 min, then 5% are impregnated with Silor water emulsion and dried to constant weight. It is proposed to use granular material in technological schemes for the posttreatment of wastewater from dissolved oil products as a load in adsorption filters.

Objective: This study was undertaken with the aim of the validate the simple isocratic metods high-performance liquid chromatographic (HPLC) for the estimation of PEG-2000-DSPE and sucrose in liposomal medicinal formulations of the phthalocyanine photosensitizer Lipophthalocyan. Methods: HPLC quantification was carried out by using of YMC-Pack Polyamine II column. The mobile phase (for sucrose: acetonitrile: water: ethyl acetate in the ratio of 450: 200: 20; for PEG-2000-DSPE: water in the ratio 10: 90) was pumped at a flow rate of 1 ml/min. Following the guidelines of the International Conference on Harmonization (ICH), the methods was validated for various analytical parameters like specificity, linearity, detection limit, quantitative limit, correctness, and accuracy. Results: The obtained results of the analysis were validated statistically. The correlation coefficient for the linearity was 0.999292, for sucrose, and 0.997650 for PEG-2000-DSPE. The methods can be assessed as correct, as the results obtained are close to the true value and the confidence interval for both methods include 100%. The coefficients of variation in both methods in determining the accuracy were less than 3%. Conclusion: The proposed HPLC methods were validated according to the ICH guidelines and results and statistical parameters demonstrated that the developed methods are sensitive, precise, reliable and simple for the estimation of PEG-2000-DSPE and sucrose in Lipophthalocyan.

The knowledge of the first-year corrosion losses of metals ( K 1 ) in various regions of the world is of great importance in engineering applications. The K 1 values are used to determine the categories of atmospheric corrosivity, and K 1 is also the main parameter in models for the prediction of long-term corrosion losses of metals. In the absence of experimental values of K 1 , their values can be predicted on the basis of meteorological and aerochemical parameters of the atmosphere using the dose-response functions (DRF). Currently, the DRFs presented in ISO 9223:2012(E) /1/ standard are used for predicting K 1 in any region of the world, along with the unified DRFs /2/ and the new DRFs /3/. The predicted values of corrosion losses ( K 1 pr ) of carbon steel, zinc, copper and aluminum obtained by various DRFs for various continental regions of the world are presented. In this work we used the atmosphere corrosivity parameters and experimental data on the corrosion losses of metals for the first year of exposure ( K 1 exp ) for the locations of the tests performed under the international UN/ECE program, the MICAT project, and the Russian program. For the first time, a comparative assessment of the reliability of various DRFs is given by comparing the values of K 1 pr and K 1 ex using graphical and statistical methods. The statistical indicators of reliability of predicting the corrosion losses of metals are calculated for various categories of atmosphere corrosivity. It is shown that the new dose-response functions offer the highest reliability for all categories of atmosphere corrosivity.

This paper presents various models (dose–response functions, DRFs) for predicting the first-year corrosion losses of structural metals for areas with marine and marine–urban (industrial) atmosphere...

The article presents research on the possibility of using oily sorption material as a secondary energy resource at industrial enterprises. Carbonate sludge from chemical treatment of thermal power plants is traditionally discharged into sludge collectors, aggravating the environmental situation in areas adjacent to power plants. Based on sludge from chemical water treatment plants of thermal power plants, a sorption material (hydrophobic carbonate sludge) has been developed for the purification of aqueous media from oil pollution. The paper considers the possibility of utilization of the oily material sorbed by the sorption material as a secondary energy resource. The characteristics of the oily sorption material are determined: elemental composition, ash content, net calorific value. A schematic diagram of utilization of oily sorption material is proposed, the volume of air and combustion products during its combustion is calculated, as well as harmful emissions and prevented environmental damage, and thermal calculation was carried out.

We studied specific antitumor activity of a liposomal drug based on tetra-3-phenylthiophthalocyanine aluminum hydroxide (lipophthalocyan) intended for photodynamic therapy. The optimal dose and protocol for photodynamic therapy with lipophthalocyan were chosen in experiments on mice: single intravenous dose of 6 mg/kg with a 5-h interval between administration and laser exposure and irradiation energy density of 400 J/cm2. A wide spectrum antitumor activity of lipophthalocyan was demonstrated in vivo for various transplantable mouse tumors (Lewis lung epidermoid carcinoma, S37 sarcoma, and colon adenocarcinoma AKATOL). The results show the possibility of using lipophthalocyan for photodynamic therapy of tumors of surface localization (skin and mucosa tumors).

The mechanism of adsorptive purification of oil refining wastewater from phenols by modified carbonate sludge of chemical water treatment (CWT) has been studied. Phenols in wastewater are extremely toxic substances. In the legislative order, the sanitary and hygienic standards set the maximum permissible concentration (MPC) of phenol in water, which is 0.001 mg/dm3. A process scheme of adsorption purification of wastewater from phenols with modified carbonate sludge, which is a large-tonnage waste from the power industry, is proposed. An adsorption filter has been designed for effective additional cleaning at Aktobe Oil Refining LLP.

It is proposed to purify industrial gas emissions from sulfur dioxide by the adsorption method. Waste from the power industry - sludge from the chemical water treatment of Kazan CHPP-1 - was used as an adsorption material. Its chemical composition is presented. Experimental studies of a new sorption material based on energy waste for gas purification from sulfur dioxide have been carried out. The kinetic dependence and isotherm of the adsorption process are obtained. The mechanism of the process of adsorption of sulfur dioxide by sorption material at different temperatures has been studied. The Gibbs free energy, differential heat, and activation energy of adsorption are determined. The economic and environmental impact of modernization of procedure for cleaning gas emissions from sulfur dioxide in sodium bisulfite production at JSC “Chemical factory named after L.Ya. Karpov” was measured.

An assay method for the excipients (sucrose, phosphatidylcholine, and cholesterol) of liposomal medicinal formulations of the phthalocyanine photosensitizer lipophthalocyan by TLC with chromatodensitometry was validated. Coefficients of standard residual deviation for establishment of linearity were 3.48 for sucrose, 1.69 for phosphatidylcholine, and 1.36 for cholesterol. The coefficients of variation for determination of similarity and intermediate precision were less than 5%. The method was shown to be reliable over a wide range of conditions for the suitability of the system.

A significant share of the hepatoprotectors pharmaceutical market is represented by innovator and generic products containing essential phospholipids. One of the main issues in pharmacotherapy is confirmation of similarity between reference and generic products, which helps to assess their interchangeability. Therefore, it seems relevant to conduct comparative studies examining the products’ formulations (content of active pharmaceutical ingredients and excipients), dosage forms and routes of administration to identify characteristics that can affect interchangeability of essential phospholipid products. The objective of the study was to analyse interchangeability of generic and reference hepatoprotectors containing essential phospholipids. The nomenclature of essential phospholipids (oral (capsules), parenteral (solution for intravenous infusion and lyophilisate for solution for intravenous infusion), and topical (gel for cutaneous use) dosage forms) is given in accordance with the State Register of Medicinal Products, information storage and retrieval systems, and library databases (eLibrary, PubMed, CyberLeninka, ResearchGate).There was a significant difference in the content of phosphatidylcholine (29—93 %) in phospholipid substances produced by different manufacturers; minor differences were found in the quantitative composition of excipients in solutions, and significant differences were observed in the composition and quantities of excipients in capsules, which is most likely attributed to different production methods. The obtained data may be used to optimise pharmaceutical development and assess interchangeability of essential phospholipid products.

Data of hygienic studies of air and soil during last 20 years have confirmed their correlating relationship with the general morbidity and a group of musculoskeletal diseases in children living in cities with the technogenic pollution of the environment. Their bones were established to grow unevenly and disproportionally, in 76% of children there have been violations in the development and growth of bones. The results of X-ray examination of hand bones in children and adolescents in the Irkutsk and Shelekhov cities are presented. Significant differences in morbidity patterns among children and adolescents including an increased incidence of musculoskeletal diseases by 5.6 in children and by 12 in adolescents have been revealed.

The article presents results of study of the impact of iodine deficiency and technogenic fluoride on the state of the thyroid gland in children. On the example of two districts of the city of Bratsk there were executed dynamic investigations (2002 and 2012), including the estimation of the pollution of ambient air and soil by fluorine compounds, levels of iodine intake by the body, the clinical examination of children aged from 5 to 7 years d and interviewing of their parents. In the course of the medical examination there were executed: physical examination by the pediatrician, endocrinologist, ultrasound examination of the thyroid gland, the determination both of serum hormone content by radioimmunoassay and urinary excretion offluorine and iodine. Concentrations of hydrogen fluoride and a solidfluorides in ambient air led to the accumulation offluoride ion in the soil. The iodine entering with drinking water and food, was established to provide only 37.5-50% of the daily requirement of iodine. Increased fluoride ion content in urine and milk teeth in children is associated with the concentrations of the fluorine-containing pollutants in the ambient air and soil. The fluoride pollution against the background of the natural iodine deficiency was established to increase the frequency of functional and morphological disorders of the thyroid gland in children.

The article proposes an adsorption technology for the treatment of salt wastewater and concentrate of reverse osmosis plants to remove sulfates and chlorides by multi-tonnage waste from the energy industry — chemical water treatment sludge formed at the wastewater pre-treatment stage. Curves of adsorption of sulfate and chloride ions by granular sorption material in dynamic conditions were obtained. According to the Shilov equation, the time and coefficient of protective action of the loading layer during adsorption purification from sulfate and chloride ions under dynamic conditions were calculated. The basic technological scheme of the pilot wastewater treatment plant and reverse osmosis concentrates of the plant at PJSC Nizhnekamskneftekhim is proposed. The economic benefit and prevented environmental damages implemented using this technology are calculated.

The bone marrow is a “niche” for stem cells; determining the bone marrow pH value is of great importance. It is very difficult, almost impossible, to carry out the intravital determination of pH. In surgical practice, there are situations when doctors have no way to save the patient's lower limb because of the threat to life. In such cases, it is possible to extract the bone marrow from the bone marrow cavity of the amputated femur and examine it. The purpose of this research was to study the acid-base balance peculiarities of the marrow of long bones and carry out a comparative analysis of the obtained data and the indicators of flat bones. The study included 40 test samples of bone marrow. Lower limb amputations were performed because of foot gangrene. Bone marrow was extracted from the femur. The marrow of flat bones was obtained by a sternal puncture. In the pH test of the sternal puncture, the data varied within the range of the blood pH, i.e., between 7.35-7.45 and 7.8. The pH and gas composition data of the sternal puncture were identical to the blood indicators. The data of bone marrow obtained from the long bone was completely different. The acid-base balance strictly ranged from 6.7 to 6.9.

An integrated approach is presented on wastewater treatment for power plants and the disposal of carbonate sludge—the waste forming at the make-up water pretreatment stage at power facilities. Usually, carbonate sludge accumulates on sludge waste sites located on the territory of power plants, which leads to an adverse impact on the environment. In addition to solid waste, the station also produces a large quantity of wastewater, which must be cleaned before being discharged into a waterbody. Concentrated wastewater is traditionally subjected to local treatment, which is associated with economic costs, while domestic and storm sewage is treated at general production wastewater treatment plants. The article proposes a wastewater biosorption technology at the Karmanovskaya GRES in which conditioned carbonate sludge is used as a sorption material. The sorption ability of carbonate sludge is confirmed by sorption isotherms of petroleum products and ammonium nitrogen. The kinetic curves obtained as a result of research confirm that biosorption wastewater treatment with carbonate sludge has a higher efficiency than conventional biological treatment. With the introduction of carbonate sludge into the aerotank for biosorption, the efficiency of wastewater treatment at the Karmanovskaya GRES increases significantly in terms of 5-day BOD, phosphate ion, chemical oxygen consumption (COD), ammonium nitrogen, and petroleum products. The use of carbonate sludge as a sorption material will improve the quality of treatment of all types of wastewater without their local treatment, which is equivalent to the wastewater’s final biofiltration. When implementing the technology of biosorption cleaning with water treatment sludge, the prevented environmental damage to the Karmanovsky reservoir will amount to 1 463 000 rubles per year in the event of oil- and salt-containing wastewater discharge from the GRES into the inlet chamber. The economic calculation of the presented technology is performed: the payback period will be 3 years and 10 months and the economic effect will be 563 000 rubles per year.

Make-up water is treated at thermal power stations (TPS) with high-pressure or superhigh pressure boilers using membrane processes implemented in ultrafiltration, microfiltration, or reverse-osmosis (RO) units. Among the criteria of the efficiency of reverse osmosis units is the amount of highly mineralized effluents (or concentrate). At present, the RO concentrate is disposed of at TPSs by discharging it into an industrial sewage system in accordance with the applicable standards on the salt content limit of waste water, routing it into a district heating network, or returning it into recirculation water supply systems, decreasing as far as possible the volume of the discharged concentrate which is to be reused, for example, in regeneration of Na-cation exchangers installed upstream of the reverse-osmosis unit. The adsorption process is proposed for treatment of the reverse-osmosis concentrate using sludge from the makeup water treatment. The characteristics of carbonate sludge are presented. The regularities of adsorption of sulfate- and chloride-anions from the RO concentrate by carbonate sludge are described. An adsorption isotherm was obtained. The mechanism of adsorption on a sorption material is proposed. The effect of pH on adsorption of sulfate- and chloride-ions by a sorption material was investigated. A system is proposed for the treatment of the concentrate from the RO units at the Kazan Cogeneration Power Station TETs-2 to remove sulfate- and chloride anions using a three-stage adsorption method with a counter-current injection of the sorbent, namely, the carbonate sludge. The calculated values of the consumption of the sorption material required to achieve the desired residual concentration of sulfate- and chloride-anions in the treated water are presented. The economic effectiveness from implementation at the Kazan TETs-2 of the adsorption treatment of the RO concentrate by carbonate sludge to remove sulfate- and chloride-ions is estimated.

Based on mathematical modeling of wastewater treatment by adsorption of petroleum products, it is shown that the sorption material “SM-5” based on carbonate sludge can be used as an accessible and effective adsorption filter loading material at wastewater treatment plants of JSC “Nizhnekamskneftekhim”. The results of mathematical modeling prove the expediency of replacing activated carbon (“Sorber” brand) with the developed sorbent “SM-5” without making structural changes to the devices of the pilot plant to minimize the anthropogenic impact of wastewater of JSC “Nizhnekamskneftekhim” on the river Kama.

Introduction.Liposomal technologies are widely used in medicine and cosmetology as a delivery system for diagnostic and medicinal products and biologically active substances. The undoubted practical importance at the stage of development of a liposomal preparation is represented by the characteristic and assessment of the sustainability of the obtained product, and special attention is paid to the study of the latter. Essentially, the methods for their preparation affect the stability of liposomes; therefore, the study of the influence of technological factors on the properties of the product at various stages of the preparation of liposomes is very important. This article is devoted to the study of the dependence of the quality of liposomes loaded with a phthalocyanine photosensitizer – thiosens, on the conditions of their production.Aim.Detection of the influence of various technological factors on the stability indicators of the liposomal form of the thiosens photosensitizer.Materials and methods.For this purpose, an analysis of the average size, polydispersity and zeta (ζ) potential of the liposomes of thiosens obtained at the stage of hydration of the lipid film, filtration of the liposomal dispersion, its extrusion, homogenization, ultrasonic treatment, and lyophilization was carried out.Results and discussion.During the preparation of a liposomal preparation, various changes in conditions can be made within the framework of the technological process. At each stage of obtaining a liposomal form, there are many critical points and parameters that must be strictly monitored and controlled. In the course of the work, the influence of technological factors on the stability of liposomal intermediate and finished products was assessed. The conditions of the most effective hydration with the formation of a stable dispersion of multilayer liposomes of thiosens and the optimal method of their grinding have been determined. It was also shown that liposomes formed after rehydration of the lyophilisate are more uniform in size and have the highest ζ-potential value in comparison with non-lyophilized liposomal dispersion.Conclusion.Using the example of a thiosens phthalocyanine photosensitizer liposomes, the influence of various technological factors on the stability of this nanostructure is shown, therefore, the characteristic and assessment of the sustainability of the resulting product according to 3 main indicators – vesicle size, polydispersity index, and ζ-potential are of undoubted practical importance.

Objective Study of embryotoxicity, teratogenicity and reproductive toxicity of the new drug Lipophtalocyan in rats. Material and Methods Studies were conducted on 210 non-inbred female rats and 105 non-inbred male rats. The drug was administered daily via i. v. injection for 48 days (males) and for 15 days (females) in 2 total doses corresponding to the therapeutic dose (TD) for mice when converted to rats and 10 TD. Results and Conclusion When mating with intact female rats, no changes in sexual behavior were observed, but the index of the ability to fertilize and conceive decreased when compared to the values of the control group by 35–40% (TD index=60%) and by 75–80% (10 TD index=20%). The index of the ability to fertilize and conceive differed from the values of the control group by 90% (TD index=5%) and by 15% (10 TD index=80%). There were no differences in the indicator of embryotoxicity and teratogenicity in intact and drug-treated female rats, compared with the control group. Lipophtalocyan has a negative effect on the male and female reproductive function in rats and has an embryotoxic effect according to the index of the ability to fertilize and conceive, as well as the indices of preimplantation and post-implantation fetal death. The drug does not have a teratogenic effect, neither it affects the physical development of offspring or the rate of maturation of sensory-motor reflexes during feeding.

Objective The current scientific research direction is development of drugs with a targeted effect on malignant tumors. One of the promising groups is indolocarbazoles and their derivatives, which can initiate various tumor cell death pathways. Russian scientists from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation has developed a new experimental drug form of the original compound LCS 1269 with cytotoxic and antiangiogenic properties, blocking vasculogenic mimicry in tumor. The study aim is the experimental drug form LCS 1269 antitumor activity on models of transplantable mouse tumors B-16 melanoma and Lewis epidermoid lung carcinoma (LLC) with different routes and modes of administration. Material and methods Female F1 hybrid mice (C57Bl/6 x DBA/2) and male and female linear mice C57BL/6 were used for management of tumor strains. Mice were obtained from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation vivarium. The antitumor effect was assessed by tumor growth inhibition (TGI) and increase of treated animal’s life span (ILS) compared to the control. Results The experimental drug form showed high antitumor activity when administered intravenously once at doses of 100 and 120 mg/kg (TGI = 98–82% and TGI = 95–77%, respectively, ILS = 24%, p p Conclusion The studies have shown that the new compound LCS 1269 in the original drug form, has a pronounced antitumor activity and significantly reduces the volume of tumor mass both on melanoma B-16 and on LLC. It allows us to recommend continue the search for sensitivity of animal transplantable tumors to LCS 1269.