Search

Introduction: In this review, the analysis of technologies for obtaining biologically active proteins from various sources is carried out, and the comparative analysis of technologies for creating producers of biologically active proteins is presented. Special attention is paid to genetically modified animals as bioreactors for the pharmaceutical industry of a new type. The necessity of improving the technology of development transgenic rabbit producers and creating a platform solution for the production of biological products is substantiated. The advantages of using TrB for the production of recombinant proteins: The main advantages of using TrB are the low cost of obtaining valuable complex therapeutic human proteins in readily accessible fluids, their greater safety relative to proteins isolated directly from human blood, and the greater safety of the activity of the native protein. The advantages of the mammary gland as a system for the expression of recombinant proteins: The mammary gland is the organ of choice for the expression of valuable recombinant proteins because milk is easy to collect in large volumes. Methods for obtaining transgenic animals: The modern understanding of the regulation of gene expression and the discovery of new tools for gene editing can increase the efficiency of creating bioreactors for animals and help to obtain high concentrations of the target protein. The advantages of using rabbits as bioreactors producing recombinant proteins in milk: The rabbit is a relatively small animal with a short duration of gestation, puberty and optimal size, capable of producing up to 5 liters of milk per year per female, receiving up to 300 grams of the target protein. [ABSTRACT FROM AUTHOR]

Introduction. Doctors of almost all specialties have to deal with the problem of pain and its relief. According to the literature, almost 30 million people daily take analgesics from the group of non-opioid analgesics, but in more than half of them 4-6 hours after taking the medication, the severity of pain is unchanged. Objective. to search for the most active molecules potential selective inhibitors of the TRPA1 ion channel with further investigation of their pharmacodynamic effects, toxicological safety, pharmacokinetic parameters and organ distribution, as well as to assess their impact on the psychoemotional state, general locomotor activity levels and anxiety in laboratory animals. Materials and methods. According to the results of in vitro tests, the most active molecule under code ZC02-0012 was selected from the pool of candidates. Further its analgesic activity was evaluated using an acetic acid-induced writhing test and a hot plate test; its anti-inflammatory activity was studied in the acute exudative paw edema model; in the open field and elevated plus-maze tests the influence of ZC02-0012 on the general locomotor activity levels and the anxiety of the laboratory animals was studied. The pharmacokinetic parameters and organ distribution of the substance ZC02- 0012 were studied using a liquid chromatograph with an operating pressure range of 0-60 mPa (Thermo Scientific Dionex UltiMate 3000). Results and discussion. According to the results of in vitro tests, it was found that IC50 of the TRPA1 selective inhibitor under laboratory code ZC02-0012 was 91.3 nmol. The preclinical studies showed that ZC02-0012 possessed pronounced analgesic and anti-inflammatory activities and absence of the influence on the behavior and anxiety of the laboratory animals. Absolute bioavailability of ZC02-0012 in rabbits was 47%, while ZC02-0012 was intensely distributed into organs and tissues with a high level of blood circulation. The highest content of ZC02-0012 is typical of liver, kidneys and lungs, the lowest - for muscle tissue. Most of the substance is undergone rapid biotransformation and excreted as metabolites. [ABSTRACT FROM AUTHOR]

Introduction: At present, enterosorbents based on mineral raw materials are in high demand among the population. However, there are no enterosorbents on the Russian pharmaceutical market on the basis of domestic mineral raw materials. Objectives: to study the pharmacological activity of enterosorbent based on montmorillonite of Russian origin under experimental conditions. Methods: The methodological approach was based on the implementation of a complex of theoretical, pharmacological, toxicological, histological, biochemical, statistical methods. Models of experimental diarrhea, acute and toxic liver damage, acute experimental pancreatitis were selected. Results and discussion: Enterosorbent based on montmorillonite Crim_04 has a dosedependent antidiarrhoeal effect, which is manifested in an increase in the time of onset of diarrhea from 50.4% to 82.6% with various models of diarrhea, a reduction in the number of defecations from 50.4% to 64.4% liquid in them. Enterosorbent on the basis of montmorillonite has a high sorption activity to E.coli enterotoxin, inhibiting the outflow of fluid into the luminal cavity by 95.1%. In addition, the use of enterosorbent Crim_04 significantly improves biochemical indices in the blood serum of rats when modeling acute and chronic liver damage and acute pancreatitis. Conclusion: The enterosorbent under the Crim_04 cipher has a dose-dependent antidiarrhea, detoxification activity, high sorption activity for E.coli enterotoxin, high therapeutic efficacy in experimental pancreatitis, most pronounced at a dose of 3320 mg / kg. It can be recommended for further complex toxicological studies and clinical trials. [ABSTRACT FROM AUTHOR]