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卷 27, 编号 7 (2024)

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Pharmaceutical chemistry

Results of research of thermosensitive properties of compositions based on chitosan lactate. Problems of biological, medical and pharmaceutical chemistry

Pyzhov V., Vlasova D., Bakhrushina E.

摘要

Introduction. The development of stimulus-sensitive drug delivery systems ("in situ" systems) is one of the actively developing trends in pharmaceutical technology. First of all, such systems provide sustained and controlled release of the active substance due to a special sol-gel transition. "In situ" systems are solutions that under various physiological conditions transition into a hydrogel. The transition of a solution into a hydrogel depends on various factors such as temperature, pH change, UV radiation, presence of certain molecules or ions. Biopolymers such as chitosan are the basis for in situ systems. Chitosan is an economically available, biodegradable and biocompatible polymer, which makes it a promising raw material for hydrogels. Solutions of chitosan salts are claimed to have stimuli-responsive properties such as pH- and thermosensitivity, however, the composition of such systems usually includes crosslinking agents that may have intrinsic pharmacological and/or toxic activities.

The aim of this study was to test the hypothesis of the thermosensitivity of chitosan lactate-based hydrogels made without crosslinking agents.

Material and Methods. In accordance with the objective, screening experiments were performed to obtain and investigate the properties of chitosan lactate, during which prototypes were obtained to test the ability of hydrogels to thermosensitive transition without auxiliary crosslinking agents and to evaluate the properties of chitosan-based hydrogels at different temperature values.

Results. As a result of the experiments carried out, it was found that the solutions studied are not capable of thermosensitive phase transition. However, it should be noted that during the experiments samples of hydrogels based on chitosan and lactic acid were obtained with different organoleptic and physical properties depending on the concentration of lactic acid.

Conclusions. Based on the results of the screening study, the hypothesis about the thermosensitive transition ability of chitosan lactate solutions without the addition of crosslinking agents was refuted. This issue requires further study using methods that allow to evaluate the underlying changes in the molecular structure of the polymer during gelation when the solution temperature is changed.

The experiments also proved the ability of chitosan to form hydrogels in aqueous solutions with low concentration of weak organic acids with pH in the range from 5 to 6.

Problems of Biological Medical and Pharmaceutical Chemistry. 2024;27(7):3-10
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Obtaining and standardization of experimental batches of "Photoran E6, lyophilizate for the preparation of solution for infusions", a drug for photodynamic therapy using hogweed leaves as raw materials

Pogartseva Y., Kauhova I.

摘要

Introduction. In recent years, there has been a sharp increase in the number of oncological diseases associated with more frequent detection of malignant neoplasms, including in the early stages. Photosensitizers are widely used for the diagnosis and treatment of oncological diseases. Already at the beginning of the twentieth century, it was discovered that a cancer cell is able to accumulate and retain colored substances [1]. In Russia, the photosensitizer "Photoran E6, lyophilizate for the preparation of an infusion solution" is widely used for the diagnosis of malignant tumors. The substance for its production is sodium chloride E6, obtained by chemical synthesis from methylpheophorbide A. which, according to the patent, is extracted from the biomass of the green microalgae Spirulina Platensis, native to Japan and California. In this regard, there is an urgent question of replacing imported intermediates with more affordable ones. For this purpose, Sosnowski's hogweed (Heraculum sosnowskyi) was chosen.

In connection with the above, the aim of this study was to obtain and standardize in terms of quality the finished drug for photodynamic therapy "Photoran E6, lyophilizate for the preparation of an infusion solution" produced from sodium chloride E6, synthesized using a new type of raw material (leaves of borscht Sosnowski).

Material and methods. The object of the study was three series of the finished medicine product (hereinafter referred to as GLS) "Photoran, lyophilizate for the preparation of an infusion solution", produced from an active pharmaceutical substance synthesized from methylpheophorbide a, obtained, in turn, from the leaves of borscht Sosnovsky as an alternative source of vegetable raw materials [2]. The quality indicators of the finished medicinal product were determined according to the methods described in the regulatory documentation in accordance with the Regulatory Documentation of the XIV and XV editions.

Results. For the research, the aseptic production of three series of GLS was carried out from the previously produced active pharmaceutical substance Sodium Chloride E6. AFS was synthesized from an intermediate obtained from the leaves of borscht Sosnowski. The standardization of the obtained series of the drug has been carried out. The possibility of using Sosnowski's hogweed as a plant raw material for the production of photosensitizers based on chlorophyll derivatives has been evaluated.

Conclusion. In the course of the study, the technology of aseptic production of GLS "Photoran, lyophilizate for the preparation of solution for infusions" was implemented. The quality indicators of the three produced batches of the finished drug have been determined.

Problems of Biological Medical and Pharmaceutical Chemistry. 2024;27(7):11-15
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Biological chemistry

Assessment of the relationship between the concentration of PSGL-1, NO-synthases and nitric oxide metabolites in the blood serum of patients with acute arterial thrombosis. Problems of biological, medical and pharmaceutical chemistry

Korotkova N., Kalinin R., Suchkov I., Mzhavanadze N., Nikiforov A., Fomina S., Alekseenko A.

摘要

Introduction. PSGL-1 is a complex protein, that provides contacts between blood cells and endothelial cells by connecting with cell-adhesion molecules selectins, and it is a universal participant in the processes of leukocyte adhesion, inflammation and immune response. The study of the possible regulation of its functioning is an urgent topic, since the process of its interactions with selectins can be a point of therapeutic application.

Aim of the study. Evaluation of the relationship between the concentration of universal ligand selectins PSGL-1, inducible (iNOS) and endothelial (eNOS) NO synthases and final metabolites of nitric oxide (II) in the blood serum of patients with acute arterial thrombosis.

Material and methods. The concentrations of PSGL-1, iNOS and eNOS in blood serum were determined, using enzyme immunoassay on an enzyme immunoassay analyzer Stat Fax 2100. The total concentration of the final stable metabolites of nitric oxide(II) (nitrates and nitrites) was determined by the spectrophotometric method modified by V.A. Metelskaya, by coloring in the reaction of diazotization with nitrite of sulfonamide present in the composition of the Griss reagent.

The results were processed, using nonparametric statistics methods of Microsoft Office Excel 2016 and IBM SPSS Statistics 26 (StatSoftInc., USA).

Results. The study revealed a statistically significant increase in the level of endothelial nitric oxide synthase and the final stable metabolites of nitric oxide in the blood of patients with acute arterial thrombosis, compared with the control group. A direct correlation of moderate severity was also found between the level of eNOS and the concentration of nitrates and nitrites. A low positive correlation was found between the concentration of PSGL-1 and the level of eNOS, and a low negative correlation was found between PSGL-1 and iNOS.

Conclusions. According to the results of the study, it can be concluded that nitric oxide, which generated by endothelial NO synthase in patients with arterial thrombosis, may have a regulatory effect on the expression or functioning of the universal glycoprotein ligand of selectins – PSGL-1, which requires more in-depth study.

Problems of Biological Medical and Pharmaceutical Chemistry. 2024;27(7):16-21
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Medical chemistry

Vitamin B₂ and its status in Vegetarians and Vegans

Ranjit R., Galchenko A.

摘要

The main goal of this review was to briefly highlight the key points of today’s knowledge about the role and metabolism of vitamin B₂ as well as to compare its status in vegans, vegetarians, and omnivores according to present data. Biologically active forms of water-soluble vitamin B₂ (riboflavin) are represented by flavin mononucleotide (FMN) and flavin adenine diphosphate (FAD), which are coenzymes in the reactions of the electron transport chain and the pyruvate dehydrogenase complex. Riboflavin is also involved in the metabolism of fatty acids, the synthesis of cholesterol and steroid hormones. Riboflavin also participates in the folate cycle. Vitamin B₂ is crucial for the metabolism of other vitamins. FMN is necessary for the formation of the active form of vitamin B₆, while FAD is necessary for the synthesis of niacin. Severe clinical insufficiency of vitamin B₂ is not common. Besides insufficient riboflavin consumption, hypothyroidism can also be a cause of vitamin B₂ deficiency as thyroxine regulates the conversion of riboflavin to its active forms - FMN and FAD. Lack of riboflavin can cause tissue damage; especially of the epithelial, reproductive, and nervous system. The variety of its manifestations is related to the fact that riboflavin deficiency also disrupts the metabolism of vitamins B₆, or PP. Similarly, riboflavin deficiency can also disrupt the folate cycle, increasing the level of homocysteine which damages vascular intima and leads to endothelial dysfunction and atherosclerosis as a result. Rapid urinary excretion of riboflavin makes it safe even if taken in a high dose, changing the urine colour into bright-yellow. This safety of riboflavin makes it unharmful to be used as an oral tracer for monitoring compliance in clinical research. Ultra-high doses of riboflavin (more than 400 mg/day) can cause diarrhoea or polyuria. The content of vitamin B₂ in animal-derived products is higher than in plant-based ones. This also determines its lower intake in vegans and vegetarians compared to omnivores. While there is a shred of evidence that plant-based diets increase the production of bioavailable riboflavin by the gut microbiota, this does not appear to be sufficient to completely compensate for the vegetarians’/vegans’ reduced dietary intake of vitamin B₂, as most of the researches point the fact that vegans and vegetarians are more prone to lack vitamin B₂ than omnivores. At the same time, it should be noted that there exists no universally adopted optimal method for assessing the status of vitamin B₂ in the body. Further research and standardization of methods may ease to assess the prevalence and risks of riboflavin deficiency in various dietary groups.

Problems of Biological Medical and Pharmaceutical Chemistry. 2024;27(7):22-31
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Platelet activation in the prognosis of cardiovascular risks in patients with psoriasis

Shelamova D., Gaikovaya L.

摘要

Psoriasis is a chronic inflammatory immune-dependent genodermatosis, mainly affecting the skin, with a prevalence in the population from 1 to 5%. The pathogenesis of psoriasis is based on Th1-dependent autoimmune inflammation, which leads to a change in the aggregation properties of platelets, increased excretion of thromboxane-A2, which worsens microcirculation processes and causes the development of endothelial dysfunction. Psoriasis is associated with a number of concomitant nosologies, such as psoriatic arthritis, depression, inflammatory bowel disease and cardiometabolic syndrome. Platelets play an important role in the development of cardiovascular diseases, as mediators of hemostasis. However, the number of publications on their pathophysiological contribution to the development of cardiovascular risks in patients with psoriasis is insignificant. Understanding the role of platelet activation in psoriasis and the correct choice of laboratory methods for their assessment will allow the timely prevention of vascular platelet disorders and prognosis.

Problems of Biological Medical and Pharmaceutical Chemistry. 2024;27(7):32-39
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Indicators of local oral immunity in users of new types of tobacco products

Ostrovskaya I., Abramova M., Parshkov V., Mamatsashvili V.

摘要

Introduction. The organs and structures of the oral cavity are among the first to come into contact with the aerosol when using elec- tronic cigarettes and heated-tobacco products, and some of the aerosol components enter various biological fluids of the mouth, inevi- tably provoking a response of the body to external influences. One of the markers of the response are immunoglobulins, and their analysis is intended to help in studying the effect of electronic cigarettes and heated-tobacco products on humans.

Objective. The aim of the study was to estimate changes in immunoglobulins A, G and M of gingival fluid, oral fluid and saliva among users of new types of tobacco products.

Material and methods. The study included 4 groups of 5 people each: regular cigarette smokers, e-cigarette users, users of tobacco heating systems and non-smokers. For laboratory studies, gingival fluid, saliva and oral fluid were taken from the subjects.

Results. Various changes in the concentration of immunoglobulins relative to the control group were observed in all groups of smok- ing patients.

Conclusion. The results may indicate inhibition of the function of local immunity both when exposed to tobacco smoke and when ex- posed to aerosol of heated-tobacco products or electronic cigarettes, which increases the vulnerability of organs and structures of the oral cavity to pathogenic microorganisms.

Problems of Biological Medical and Pharmaceutical Chemistry. 2024;27(7):40-45
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Problems of experimental biology and medicine

Hepatoprotective effect of golden volodushka (Bupleurum Aureum L.) Herb extract of dry in experimental toxic hepatitis in rats. Problems of biological, medical and pharmaceutical chemistry

Kurmanova E., Ferubko E.

摘要

Introduction. The search for new medicines, including those of plant origin, for the treatment of diseases of the hepatobiliary system is relevant and timely. A promising source for the development of hepatoprotective drugs is golden volodushka (Bupleurum aureum L.). To date, a large evidence base has been accumulated for the biochemical study of this plant, its pharmacological activity has been scientifically proven. Good stocks of golden volodushka in the wild, the simplicity of its harvesting and the possibility of cultivation were noted. The VILAR State Medical University has developed a method for obtaining volodushka golden herb extract of dry.

Aim. The study of the pharmacotherapeutic efficacy of volodushka golden (Bupleurum aureum L.) herb extract of dry in case of liver damage under experimental conditions.

Material and methods. In the studies, white non-linear male rats with a body weight of 180-200 g were used. Volodushka extract was studied at doses of 50 and 100 mg/kg. The comparison drug was silimar at a dose of 100 mg/kg. Experimental CCl4 – induced hepatitis in rats was caused by a single subcutaneous injection of 50% carbon tetrachloride oil solution one hour after the last administration of the studied extract and the comparison drug. After 48 hours, blood was taken from the tail vein of rats, serum was obtained and its biochemical analysis was carried out. Next, the rats euthanized in a CO2 chamber and the liver extracted for pathophysiological evaluation. Tetracycline hepatitis was caused by intragastric administration of tetracycline to animals at a dose of 500 mg/kg. Then, after 48 hours, blood was taken from the animals, serum was obtained and its biochemical analysis was carried out.

Results. Volodushka golden grass dry extract on a model of carbon tetrachloride hepatitis exhibits a hepatoprotective effect, which is confirmed by a comparative pathophysiological study and a study of the activity of enzyme markers of the morphofunctional state of the liver in rat blood serum. In the tetracycline hepatitis model, the studied extract also has a hepatoprotective effect, which is confirmed by biochemical studies.

Conclusions. Studies of volodushka extract in conditions of experimental liver lesions have shown that the studied extract in experimental therapeutic doses has a pronounced hepatoprotective effect and is promising for the creation of a herbal medicine for the prevention and treatment of diseases of the digestive system.

Problems of Biological Medical and Pharmaceutical Chemistry. 2024;27(7):46-52
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Effect of monoamine oxidase inhibitor on free radical oxidation in rat kidneys with alloxan-induced hyperglycemia. Problems of biological, medical and pharmaceutical chemistry

Sinitskii A., Noskova V., Vinel P., Shatrova Y., Polevshchikova E.

摘要

Introduction. One of the most severe and dangerous complications of diabetes mellitus (DM) is diabetic nephropathy, the leading pathogenetic factor of which is considered to be prolonged hyperglycemia with the development of oxidative stress. Several leading redox-dependent mechanisms of diabetic nephropathy have been described, among which an important role is played by oxidases, as a key link in the redox balance in podocytes. The kidneys are characterized by high activity of monoamine oxidases (MAO), which are active producers of hydrogen peroxide. Meanwhile, the contribution of monoamine oxidases to the development of oxidative stress in the kidneys under conditions of prolonged hyperglycemia remains unexplored.

Purpose of the study – to assess the contribution of monoamine oxidases to the development of oxidative stress in the kidneys under conditions of long-term hyperglycemia induced by alloxan.

Material and methods. The study was conducted on 111 Wistar rats of both sexes, weighing 180–250 grams. Diabetes mellitus was modeled by intraperitoneal administration of alloxan monohydrate at a dose of 163 mg/kg. To assess the contribution of MAO-B to the development of oxidative stress, the selective MAO-B inhibitor selegiline was used at a dose of 5 mg/kg. Throughout the experiment, glycemia and body weight of the animals were monitored. Animals were removed from the experiment on the seventeenth day. The levels of oxidative modification of proteins, lipid peroxidation products, as well as the activity of monoamine oxidases A and B in kidney homogenates were determined by spectrophotometric methods.

Results. It was found that on the fourteenth day from the moment of alloxan administration, signs of oxidative stress (increased oxidative modification of proteins) are revealed in the kidneys. The results of the correlation analysis demonstrate direct correlations in the "Alloxan" group of animals between the level of blood glucose on the 14th day of the experiment and the levels of products of oxidative modification of proteins, as well as the activity of MAO-B and the levels of products of oxidative modification of proteins and primary heptane-soluble lipid peroxidation products in kidneys. The absence of this kind of relationship in the group of animals that additionally received a MAO-B inhibitor ("Alloxan + selegiline").

Conclusions. The results of the study confirms the contribution of the intensification of free radical oxidation to the development of diabetic nephropathy during prolonged hyperglycemia, on the one hand, and the prooxidant effect of MAO-B on the other.

Problems of Biological Medical and Pharmaceutical Chemistry. 2024;27(7):53-58
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