Currently, the study of promising “biogenic stimulants” that exhibit pathogenetic effects in relation to various diseases continues. The first results of studies of peptide “biogenic stimulants” based on human placenta extracts (HPE) were obtained by Prof. Filatov VP in the thirties of the 20th century. Currently, through modern methods of postgenomic pharmacology (including high-precision mass spectrometry, enzyme-linked immunosorbent assay and sequencing), it becomes possible to obtain new data on the structure and functions of peptide extracts, which indicates the molecular pharmacological mechanisms of their action. Analysis of peptide fractions of individual standardized ENPs and the results of clinical studies of these ENPs indicate a wide range of clinical applications of ENPs: (1) liver diseases; (2) viral diseases — COVID-19, etc.; (3) diseases accompanied by iron overload and hyperferritinemia; (4) chronic fatigue syndrome; (5) skin diseases; (6) joint pathologies; (7) acceleration of wound healing; (8) diseases associated with the female reproductive system.

Mass spectrometric sequencing of peptides in Laennec indicated the presence of 5 peptides in the drug, the biological activity of which may determine the antibacterial properties of the drug. The most significant result of this study is the presence in Laennec of a fragment of the antibacterial peptide cathelicidin (LL-37), an important vitamin D-dependent factor of innate immunity. Other Laennec peptides help reduce excess inflammation by inhibiting the activity of the NF-kB protein, which mediates the effects of TNF-α.

Palm oil is a component of most food products, characterized by a high content of palmitic and oleic acids, an excess of which leads to the formation of tripalmitins, practically do not respond to enzymatic hydrolysis by lipoprotein lipase and predetermine the development of obesity, type 2 diabetes mellitus and atherosclerosis. This paper presents the results of a study of the drug Laennek, produced on the basis of standardized hydrolysates of the human placenta (HRP). The use of HRP under the influence of excessive consumption of palm oil in the diet led to a significant decrease in markers of liver dysfunction (ALT), which increase with an enriched diet of refined palm oil (bilirubin, total protein, ALT, AST). The hepatoprotective effect of Laennek was confirmed by the results of histological and biochemical studies indicating a decrease in the severity and prevalence of fatty liver dystrophy.

The aim. Study of pharmacodynamic parameters and confirmation of pharmacodynamic equivalence (bioequivalence) of the drugs Antareit® (INN: magaldrate), chewable tablets, 800 mg (Valenta Pharm JSC, Russia) and Riopan (INN magaldrate), chewable tablets, 800 mg (Takeda GmbH, Germany). Material and methods. An open randomized crossover study was conducted to investigate the pharmacodynamics of the study drug Antareit® and the reference drug Riopan, assessing their bioequivalence after taking 2 chewable tablets of the study or reference drug 3 times a day. The study involved 40 healthy volunteers who were randomized into 2 groups of 20 people depending on the sequence of drug administration in study periods I and II. Intragastric acidity was measured with a pH-probe within 30 minutes before and for one hour after taking the study drugs. Based on the data obtained, 90% confidence intervals (CI) were calculated for the pharmacodynamic parameter AUCABL, reflecting the area above the baseline pH. The safety of the study drugs was assessed by the frequency and severity of adverse events (AEs). Results. Statistical analysis showed that the 90% CI for the ratio of the mean values of the AUC ABL parameter of the study drug to the reference drug did not fall below 80% (90% CI: 80.55–119.49). During the study, 18 adverse events (AEs) were reported in 15.4% (6 of 39) of volunteers in the safety population, and there were no statistically significant differences in the incidence of AEs between groups, nor in the incidence of AEs depending on the drug taken. Conclusion. The studied drugs are pharmacodynamically equivalent and have a similar safety profile when administered repeatedly.

Relevance. To introduce the GK-2 compound into clinical practice, it is necessary to conduct a preclinical study of its pharmacokinetics, in particular, the distribution of the studied drug in organs and tissues. The aim is to study the tissue availability of a new original compound GK-2 in rats after its intraperitoneal administration. Methods. Quantitative determination of GK-2 in blood plasma and organ/tissue homogenates of rats was carried out by high-performance liquid chromatography with mass spectrometric detection. Results. The distribution of GK-2 in organs and tissues with varying degrees of vascularization was studied in rats. It was found that after a single intraperitoneal injection of GK-2 at a dose of 150 mg/kg, the studied compound was recorded in blood plasma for 2 hours, its half-life (t1/2el) was 0.4 hours. In organs and tissues, GK-2 was detected from 1.5 to 2 hours. The tissue availability of GK-2 in the liver — blood plasma system was 18.68; "kidneys — blood plasma" — 1.26; "spleen — blood plasma" — 0.68; "skeletal muscles — blood plasma" — 0.31. For the target organ, the brain, the tissue availability was 0.24. In the brain, the time to reach the maximum concentration of GK-2 (0.77 mcg/g) was 0.34 hours. It was found that GK-2 is excreted more slowly from the brain (t1/2el was 0.75 h) than from other organs and tissues (from 0.31 h for the spleen and up to 0.47 h for the kidneys).

Relevance. The increase in the number of cases of multidrug-resistant tuberculosis (MDR-TB) determines the relevance of the development of new anti-TB drugs (ATDs). Determining the pharmacokinetics of a drug in the context of MDR-TB therapy is an integral part of the study of the original drug. Objective. Evaluation of the pharmacokinetic properties of a new original drug, thiozonide, in patients with MDR-TB with multiple doses of the drug. Methods. Thiozonide was used in patients with a verified diagnosis of MDR-TB as part of a clinical trial according to protocol No. THIO22 "Multicenter 12-week doubleblind, randomized, placebo-controlled clinical trial on the selection of optimal dosages of the drug thiozonide, capsules (CJSC Pharm-Sintez") for against the background of standard anti-tuberculosis chemotherapy in patients diagnosed with pulmonary tuberculosis with multidrug-resistant or extensively drugresistant Mycobacterium tuberculosis” (permission of the Ministry of Health of the Russian Federation No. 661 dated 11/24/2014). Results. The pharmacokinetic characteristics of thiozonide were determined during its repeated use in patients diagnosed with pulmonary tuberculosis with multidrug-resistant or extensively drug-resistant mycobacterium tuberculosis, receiving standard anti-tuberculosis chemotherapy, by HPLC with mass spectrometric detection. The time to reach the maximum concentration T max of thiozonide with repeated administration at a dose of 200 mg, 400 mg and 600 mg was 4.21 ± 1.23 hours, 4.9 ± 1.08 and 5.29 ± 0.91, respectively; the half-life T1/2 for the same dosages of the drug was 7.84 ± 1.86, 7.56 ± 1.92 and 6.3 ± 2.12 hours, respectively. The maximum concentration of thiozonide after taking the drug thiozoinide by volunteers was Cmax was observed at the level of 1386.89 ± 533.68 ng / ml in the group taking 200 mg of thiozonide per day, 2684.48 ± 712.40 when taking the drug at a dosage of 400 mg and 5558, 99 ± 2143.81 – at a dosage of 600 mg. Conclusion. A linear dependence of the maximum concentration and the area under the pharmacokinetic curve on the dose taken and also the average concentration of thiozonide in the blood plasma of patients with pulmonary tuberculosis with multidrug resistance of the causative agent of the disease was revealed.

Relevance. Coenzyme Q10 is one of the main components that maintain the balance of the body's redox regulatory system. Although some studies have examined plasma concentrations of CoQ10 in various diseases, the distribution of ubiquinol and ubiquinone, as well as the redox state of CoQ10, remain largely unexplored. The purpose of the study. The purpose of the study was to study the ratio of ubiquinone and ubiquinol concentrations in patients with chronic heart failure (CHF) administrating the antioxidant ethylmethylhydroxypyridine malate and the domestic drug ubidecarenone (CoQ10 drug). Methods. The study included 58 patients with functional class (FC) of CHF 0−III (according to NYHA), who were divided into 2 groups for subsequent assessment of the effect of ethylmethylhydroxypyridine malate and ubidecarenone on endogenous plasma concentrations of total CoQ10, ubiquinol and ubiquinone. The concentrations of the studied substances were determined by HPLC-MS/MS in the multiple reaction monitoring mode. Results. The study revealed that with additional administration of the drug ubidecarenone, there was an increase in the concentration of coenzyme Q10 (+25.0 Δ%), a significant increase in the concentration of ubiquinol (+43.4 Δ%), as well as a sharp increase in redox state (+74.6 Δ%) compared to the control group. During administration of ethylmethylhydroxypyridine malate in addition to standard therapy, patients experienced a statistically significant increase in the concentration of coenzyme Q10 (+20.22 Δ%), a significant increase in the concentration of ubiquinol (+25.0 Δ%) and ubiquinone (+17.7 Δ%) according to compared with a control group receiving standard therapy. Conclusion. With the additional administration of ethylmethylhydroxypyridine malate and ubidecarenone to standard therapy, a statistically significant increase in the concentration of total CoQ10 is observed. However, when administrating ubidecarenone, a sharp increase in the redox state of CoQ10 is observed due to its reduced form — ubiquinol. While during administration of ethylmethylhydroxypyridine malate, it is observed an unreliable but positive trend towards an increase in the redox state of CoQ10 due to a statistically significant increase in the concentration of both ubiquinone and ubiquinol.

Relevance. Acute toxicity testing is a common procedure for preclinical safety testing of potential agents. The purpose of this study was to study the acute toxicity of the compound GIZH-272, a new dibenzofuran oxime derivative with anti-ischemic and anticonvulsant effects. Methods. The compound was administered to mice intraperitoneally and orally once. Within 14 days, the condition of the animals was monitored, clinical manifestations of intoxication were recorded, and changes in the dynamics of body weight and its growth were recorded. Results. It was found that the test compound at maximum doses did not lead to the death of mice. Therefore, the data obtained according to the classification of Sidorov K.K. (1973), make it possible to attribute GIZH-272 to the 5th class of toxicity — "practically non-toxic substance". In accordance with GOST 12.1.007-76, the GIZH-272 compound belongs to the 4th hazard class (low-hazard substance) for oral administration.

Introduction. Gout treatment drugs are widely represented on the pharmaceutical market of the Russian Federation, including those with INN febuxostat. These drugs differ in excipients composition, in the dosage form (tablets and capsules) and production technology. The Dissolution Kinetics Test was chosen to assess the rate and extent of active ingredient release for drugs with INN febuxostat for different manufacturers as in vitro test dissolution allows to suggest the release from the dosage form in vivo. The rate and percent of active substance release are factors that have a direct impact on the bioavailability of drugs. Drug release was studied in a phosphate buffer solution pH 6.8, sampling was carried out at time points 0 min, 5 min, 10 min, 15 min, 20 min, 30 and 45 min. The analysis of the obtained solutions was carried out using the UV spectrophotometry method at a wavelength of 317 nm. The comparison of dissolution profiles was carried out in accordance with the requirements of Decision of the Council of the Eurasian Economic Commission dated November 3, 2016 N 85 "On approval of the Rules for conducting bioequivalence studies of medicinal products within the framework of the Eurasian Economic Union". The purpose of the study. The purpose of this study was to compare the kinetics of the release of the active substance febuxostat from drugs registered in the territory of the Russian Federation in the form of tablets and capsules. Materials and methods. Drug release studies were performed using the Sotax dissolution tester AT Xtend, Switzerland. Each drug was analyzed in 12 repetitions in a pH 6.8 phosphate buffer dissolution medium, on a "Paddle apparatus", special sinkers were used for capsule dosage forms. The selected samples were analyzed on a Shimadzu UV 1800 UV spectrophotometer, Japan, at a wavelength of 317 nm. Results. Dissolution profile studies for three drugs with the active substance febuxostat were conducted in a phosphate buffer solution pH 6,8. For the studied drugs, the release of febuxostat was observed to be more than 85 % at 15 minutes. The release profiles can be recognized as equivalent without further mathematical processing. Conclusion. Based on the results of dissolution profile studies, no differences were found in dissolution profiles of febuxostat from drugs with different dosage forms (tablets and capsules).

Previously at the Zakusov Research Institute of Pharmacology the first dipeptide ligand TSPO, the compound N-phenylpropionyl-L-tryptophanyl-L-leucine amide (laboratory code GD-102), was designed and synthesized. The anxiolytic activity was detected for this compound at the doses 0.01–1.0 mg/kg intraperitoneally (ip) in mice. Dipeptide GD-102 also possessed antidepressant-like activity at the doses 0.01 and 0.05 mg/kg ip in BALB/c mice in the Porsolt forced swim test. The ligand properties of dipeptide GD-102 to TSPO were confirmed by pharmacological inhibitory analysis and molecular docking. This work is devoted to the development of the optimal scheme for the synthesis of the GD-102. 3 methods were tried — 1 activated succinimide esters method, 2 activated pentafluorophenyl ethers method and 3 imidazolide method. These three synthesis schemes have been compared in terms of yield and optical purity of the final product. It was shown that the optimal synthesis scheme is the first one, using succinimide esters.

Cardiac arrhythmias are the most common pathologies of the cardiovascular system. Allapinin® and Allaforte® from “Pharmcenter VILAR” are effective IC-class antiarrhythmic agents. The main component of these drugs is a pharmaceutical substance with INN: lappaconitine hydrobromide, which in addition to lappaconitine hydrobromide itself, contains impurities of other diterpene alkaloids. This work is devoted to a detailed analysis of the alkaloid composition of a new pharmaceutical substance isolated from roots and rhizomes, as well as from the aerial part of plants of the genus Aconite (monkshood, wolfsbane) of the Ranunculaceae family (buttercups) using chromato-mass spectrometry and NMR spectroscopy. In addition, an assessment was made of the quantitative ratios of alkaloids in several samples of pharmaceutical substances isolated from different batches of medicinal plant raw materials.