Problems of Biological Medical and Pharmaceutical Chemistry

Introduction. The most popular and affordable method for assessing the degree of drug release (DR) is the method of dialysis through a semipermeable membrane, the effectiveness of which is determined by the choice of a suitable membrane. With various positive aspects of the use of natural and synthetic membranes, their use has a number of limitations, the main of which for natural membranes are differences in lipid composition depending on the type of animal and even skin areas, for synthetic membranes – the exclusion of the influence of DR interaction processes. Considering that phospholipids and cholesterol form the basis of cell membranes, and lecithin is a similar combined compound, it seems possible to create model membranes based on lecithin.

The aim of the study was to create lecithin membranes similar in functional properties to natural membranes, but with optimal physico-chemical parameters, simplicity and accessibility of manufacture, and a comparative assessment of the degree of release of acidic polysaccharides (beet pectin, sodium alginate) through lecithin membranes.

Material and methods. Lecithin membranes are obtained by impregnating dense fine-porous paper filters "blue ribbon" with a diameter of 5.0–20.0 cm in a 6.3% solution of lecithin in 95% ethanol for 48 hours.

Results. Comparable results of determining the reduced degree of dialysis of polysaccharides through lecithin membranes in comparison with the parietal sheet of the rat peritoneum, the use of isotonic sodium chloride solution and physiological temperature make it possible to simulate the conditions as much as possible in vivo in the study of the bioavailability of DR.

Conclusion. Lecithin membranes are characterized by high porosity, minimal thickness, resistance to decomposition processes, uniformity of composition and properties, stability of lipid composition, the possibility of varying surface area, volumes of dialyzable solutions, manufacture as needed or for future use, ease of manufacture, shelf life at room temperature, availability and low consumption of materials and reagents. This does not require slaughtering animals and laborious separation of the membrane layer from the muscle layer, as well as cleaning.

Introduction. OATP1B1 and OATP1B3 are influx proteins belonging to the SLC transporter family and providing substrate transport into hepatocytes. The mechanisms of their regulation are currently being actively studied.

Aim. To study the effect of sex hormones on the expression of the SLCO1B1 and SLCO1B3 genes encoding OATP1B1 and OATP1B3, respectively.

Material and methods. The study was performed on the HepG2 cell line. Estradiol, progesterone, and testosterone were added to the cells at concentrations of 1 nM, 10 nM, 100 nM, 1 μM, 10 μM, 100 μM and incubated for 24 h. After incubation, total RNA was isolated and gene expression was tested by real-time polymerase chain reaction.

Results. Estradiol at concentrations of 10 and 100 μM increased the expression of the SLCO1B1 gene encoding OATP1B1 by 50.9% (p=0.027) and 60.2% (p=0.009), respectively. Testosterone at a concentration of 1 μM increased the expression of the SLCO1B1 gene by 53.2% (p=0.014), at a concentration of 10 μM – by 62.7% (p=0.004), at a concentration of 100 μM – by 66.7% (p=0.0026). Estradiol at concentrations of 1, 10 and 100 μM increased the expression of the SLCO1B3 gene by 80.3% (p=0.0021), 115.6% (p<0.001) and 115.5% (p<0.001), respectively. Testosterone at concentrations of 1, 10 and 100 μM increased the expression of SLCO1B3 by 53.2% (p=0.029), 62.7% (p=0.007) and 66.7% (p=0.032), respectively, compared to the control.

Conclusion. Thus, it was established that estradiol and testosterone increase the expression of the SLCO1B1 and SLCO1B3 genes, and progesterone does not affect them.

Introduction. The development of means to create a wound dressing that promotes rapid healing through the release of biologically active substances (BAS) and the prevention of infection is a relevant research area. The use of biodegradable materials with strong regenerative properties is of particular interest. Gelatin has the most of these properties and can be considered as a promising basis for the creation of biodegradable wound dressings with regenerative activity.

Aim of the study. The aim of the study is to investigate the regenerative and anti-inflammatory properties of a biodegradable gel wound dressing.

Material and methods. A gel based on fish gelatin with the addition of broadleaf plantain extract (Plantago major L.) at a concentration of 10% and 4-hydroxybenzoic acid methyl ester at a concentration of 0.05% was studied. The regenerative activity of the gel was evaluated in experimental studies on laboratory animals with a simulated thermal burn of the skin. The anti-inflammatory activity of the gel was assessed by the level of total leukocytes and inflammatory markers in blood serum.

Results. The application of the biodegradable wound dressing in the form of a gel has a regenerative effect, which was confirmed by an increase in the rate of epithelialisation and a reduction in the wound surface area by almost 1.5 times compared to the control values (p˂0.05). The pronounced anti-inflammatory activity of the gel was confirmed by a 1.2-fold reduction in total leukocyte count compared with the untreated burn group, a 2.4-fold reduction in C-reactive protein levels (p<0.05) and a 66.2-fold reduction in procalcitonin levels (p<0.01) compared with the untreated control group.

Conclusion. The biodegradable wound dressing based on fish gelatin with broadleaf plantain extract has a pronounced regenerative and anti-inflammatory effect, which is accompanied by accelerated release of necrotic tissue from the wound, reduction of the burn wound area, acceleration of epidermal restoration and healing of the affected skin, reduction of the total number of leukocytes and the level of pro-inflammatory markers and, as a result, reduction of the treatment time on the burn wound model.

Ethylene glycol (EG) and diethylene glycol (DEG) are toxic compounds that, when ingested, even in small amounts, cause severe systemic damage, including metabolic acidosis, acute kidney failure, neurological disorders, and other life-threatening conditions. These compounds pose a particular danger to children, as evidenced by numerous cases of mass poisonings from medicines contaminated with EG and DEG, reported globally in recent years. The presence of glycols in medicines results from the adulteration of excipients or the use of substandard ethoxylated substances. In response to recent poisoning incidents, regulatory agencies worldwide have tightened standards, setting a maximum allowable limit of 0.1% for each contaminant. In connection with the current situation, it becomes obvious that rigorous quality control of both excipients and finished products is necessary for the presence of dangerous impurities of EG and DEG. This article reviews and compares modern analytical methods for EG and DEG detection in medicines, focusing on three widely adopted and officially approved techniques:

• Thin-Layer Chromatography (TLC) – a simple and cost-effective method used primarily for screening studies;
• Gas Chromatography with Flame Ionization Detection (GC-FID) – the most accurate and reliable method recommended by WHO and the world's leading pharmacopoeias;
• High Performance Liquid Chromatography with Refractive Index Detection (HPLC-RID) – an alternative method that complements existing approaches.

Aspects of the application of each of these methods, including sample preparation and chromatographic separation parameters, are considered. Attention is also paid to the interfering effect of excipients on the analysis results and the need to adapt techniques for each drug.

Introdction. Common chicory (Cichorium intybus L.) is a valuable plant containing a sum of biologically active substances with various biological properties. The study of antimicrobial activity of its above-ground part deserves special attention, as it may open new opportunities for the use of this crop both in the diets of farm animals and in the creation of medicinal preparations and functional food additives.

The aim of the work was to study the antimicrobial activity of aqueous extracts from grass and leaves of common chicory and dry extracts and meal obtained from them to determine the possibility of complex use of raw materials of this plant.

Material and methods. The objects of study were raw material, meal and dry extract obtained from grass and leaves of common chicory. Experimental studies were carried out using generally accepted microbiological methods of research with respect to the following strains of pathogenic bacteria: Staphylococcus aureus 6538P, Escherichia coli (ATCC 25922), Proteus vulgaris (ATCC 6896), Pseudomonas aeruginosa (ATCC 9027), mycelial Microsporum canis 352 and yeast-like Candida albicans ATCC 10231) fungi.

Results. Aqueous extracts from grass and leaves of common chicory and their meal had the same bacteriostatic activity against S. aureus 6538 P, E. coli (ATCC 25922), P. vulgaris (ATCC 6896), P. aeruginosa (ATCC 9027). Only aqueous extracts from the raw materials showed fungistatic activity against yeast-like and mycelial fungi; the meal did not possess such properties. Dry extracts had bacteriostatic and fungistatic activity, with the dry extract of chicory herb being 2-4 times more active than the leaf extract of cultivated common chicory.

Conclusions. Common chicory is a valuable and promising plant that can be used as a medicinal plant raw material for the creation of biologically active food additives, as well as feed additives for farm animals.

Introduction. In the North Caucasusи Campsis radicans L. is cultivated as an ornamental plant. It is widely used in folk medicine in Asian countries; however, its chemical composition has not been sufficiently studied.

The aim of this work was to determine the content of phenolic compounds by capillary electrophoresis in extracts from C. radicans leaves and flowers obtained by extracting the raw material with 40% and 70% ethyl alcohol.

Material and methods. Objects of study: C. radicans leaves and flowers collected in the village of Zayukovo, Baksan district, Kabardino-Balkarian Republic in July – August 2022. Determination of phenolic compounds in the analyzed extracts was carried out using a KAPEL-105M capillary electrophoresis system.

Results. The following phenolic compounds were identified in the studied extracts: vanillic, sinapic, syringic, p-coumaric, ferulic acids, luteolin and rutin. It was found that all the extracts from leaves and flowers contain sinapic acid in almost equal amounts.

Conclusions. The obtained results allow us to predict the antioxidant activity of the studied extracts due to the content of lilac and sinapic acids, which have a spatially hindered phenolic hydroxy group.

Introduction. According to the Order of the Ministry of Health of the Russian Federation dated June 30, 2022 No. 453n "On approval of the Procedure for dispensary supervision of a person suffering from chronic and prolonged mental disorder with severe persistent or often aggravated painful manifestations", it is required to measure the concentration of drugs in patients 2 times a year. The heads of the executive bodies of the subjects of the Russian Federation in the field of healthcare are recommended to organize control over the treatment of socially dangerous patients. The list of medicines to be controlled includes: chlorprotixen, thioridazine, respiridon, triftazine, haloperidol. chlorpromazine, carbamazepine, quetiapine, etc. There is an urgency in the development of quantitative determination techniques both for the observation of persons suffering from mental disorders and for the production of research in medical toxicology. Validation of the methods serves as a guarantee that the results of the analysis are reliable and accurate.

Goal – to develop and validate a methodology for the quantitative determination of carbamazepine by high-performance liquid chromatography (HPLC) with diode-matrix detection using an internal standard.

Material and methods. The quantitative determination of carbamazepine by HPLC was carried out in model mixtures of blood serum and urine after introducing an internal standard into them and extraction with chloroform. The following are determined: linearity, specificity, correctness, precision (under conditions of repeatability). The minimum analyzed concentration of carbamazepine is 0.50 mcg/ml, the maximum is 50.0 mcg/ml.

Results. It was established: the dependence graphs are linear in nature, for blood serum the correlation coefficient was 0.99933, for urine – 0.99900; the methods are specific, which is confirmed by the absence of extraneous peaks in extracts from "blank" samples of blood serum and urine, coinciding in retention time with the studied substances; indicators of relative standard deviation they do not reach 7%, the relative error is less than 8%.

Conclusions. The features of the quantitative determination of carbamazepine by HPLC using an internal standard have been studied. The obtained results are reproducible and, with the help of validation, their suitability for therapeutic monitoring, chemical and toxicological research, and forensic chemical analysis has been confirmed.

Introduction. One of the promising directions of antioxidant chemistry development is the synthesis and study of specific activity of organic compounds based on sulphur. The most active research in this area is carried out at the Department of Chemistry of FSBI HE Novosibirsk State Pedagogical University together with the Research Institute of Antioxidant Chemistry.

Aim – to select and study the spectrophotometric and titrimetric characteristics of sulfur-containing water-soluble antioxidant TF-7 and compare them.

Material and Methods. In this study, the spectrophotometric characteristics of a novel water-soluble antioxidant, TF-7 (3-(4-hydroxy-3,5-dimethylbenzylthio)potassium propionate), were investigated. A spectrophotometric methodology was employed for the purposes of quantitative and qualitative analysis. The titrimetric methods of acidimetry, iodometry and mercurimetry were selected for comparative analysis of the new substance TF-7.

Results. The preliminary studies indicated that the spectrophotometric analysis of the pharmaceutical substance in the ultraviolet (UV) spectrum exhibited a maximum at a wavelength of 276 ± 2 nanometres (nm). The mercurimetry method was identified as the most accurate of the selected titrimetric methods for the determination of TF-7, with an equation of y=1,014895x+0,0000001 and a correlation coefficient of 0.9996.

Сonclusion. The characterisation of spectrophotometric and titrimetric methods of analysis for the quantification of the new substance TF-7 has been developed. It has been demonstrated that the aforementioned methods of obtaining qualitative and quantitative characteristics for spectrophotometric determination and mercurimetry titration are optimal for analysis in model solutions.