M. M. Kuznetsova

The aim of the work was to study the legal aspects of the legislative regulation for manufacturing medicines in a pharmacy organization. Materials and methods. Databases of ConsultantPlus, Cyberleninka, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Center for Biotechnology Information (NCBI), PubMed, e-library, WIPO Lex were used as search sources. The search was based on the following keywords and phrases: intellectual property, pharmacies+invention, patent, drugs, extemporal+production, orphan+diseases, as well as their Russian counterparts. 133 sources of information, including scientific articles and regulations, were found out; 50 have been included in this review. The analysis of information sources published from 2013 to 2023, was determined by the peculiarities of legislation changes in this area. Results. The article provided an overview of modern, including regulatory practice, pharmaceutical manufacturing in the Russian Federation, and also analyzed the benefits of this activity for the medical community, patients and the state. At the same time, the individualization of drug treatment has made it possible to work out systemic solutions for developing drug therapy methods for special groups of patients for whom the economic feasibility of a pharmaceutical registration and launching such drugs onto the market has been brought into challenge. In addition, pharmacy manufacturing is an accessible tool in the study of the drugs prescribed by a doctor not in accordance with the instructions for medical use (off-label) or in the dosage forms/dosages that are not on the market. Extemporaneous manufacturing can be also a part of the process of “repositioning” drugs on the market, subject to compliance with the requirements for pharmacy manufacturing and control of the prescribed drugs safety. The possibility of pharmaceutic drug manufacturing also makes it possible to partially resolve issues related to intellectual property. As a result of the carried out analysis, the following hypothesis was confirmed: the legislative changes have a similar legal assessment both in Russia and abroad and correspond to the legal practice in resolving intellectual property issues in relation to pharmacy organizations. Conclusion. The renewal of a pharmacy production will improve the availability of the drug care to the population, taking into account individual dosages and dosage forms in various therapeutic areas, and can also become a tool for repositioning drugs or clinical testing of new molecules for rare incurable diseases.

The accessibility and pharmaceutical care coverage are linked to political, economic and managerial decisions. That fact necessitates the evaluation of the state programs results in the field of the drug provision. The aim of the work was to assess the quantitative results of the implementation of the High-Cost Nosologies program in the Russian Federation from 2008 to 2023 to determine further vectors of its improvement. Materials and methods. The regulatory base of the work was made up of the Russian Federation legislation in the field of the drug provision. The open sources were used as the research information base for the data collection and analysis: reports of federal and regional executive authorities, materials of specialized conferences, results of published studies. Results. The drug coverage under the High-Cost Nosologies (VZN) program is provided for 14 nosologies, 11 of which are classified as orphan diseases. Since its implementation, the HCNs program has been expanded twice by including new nosologies in 2019 and 2020. As of 01 October 2023, the number of patients in the Federal Register of VZN was 263 721 people, which was 13.58 times greater compared to 2008. The drug provision is carried out according to the list of 47 INNs. The amount of funding for the program increased from RUB 32 bn in 2008 to RUB 87.96 bn in 2023. The most resource-intensive nosologies include hemophilia, multiple sclerosis and oncohematology. Conclusion. The main quantitative characteristics of the implementation of the HCNs program and the identified vectors for its further improvement have been analyzed in this study. The results obtained can be used to conduct analytical studies, including the ones within nosologies and nosological groups included in the program, in order to optimize a pharmaceutical care. The focus of improving the implementation of the VZN program is related to the improvement of the legal framework, a patient treatment paradigm and approaches to its financing.

PURPOSE: To assess research directions of the Mesenchymal stem cells (MSCs) injections in traumatology and orthopaedics. METHODS: The study monitored the protocols of randomised controlled trials (RCTs) and systematic reviews (SRs) investigating mesenchymal stem cell (MSC) injections for various traumatological and orthopaedic conditions. Relevant RCT protocols were identified through searches of ClinicalTrials.gov, International Clinical Trials Registry Platform, EU Clinical Trials Register databases for RCTs and SRs were obtained from PROSPERO. The databases were searched from their inception to December 2023. RESULTS: A total of 449 clinical trials were identified. At the time of the study, 159 (35.4%) trials had been completed, and only 56 (12.5%) had published results in peer-reviewed journals. Data on clinical trial completion were normally distributed (p = 0.145). The duration for trial completion was 40.6 ± 26.5 months (range: 1 to 153 months). The most commonly investigated indications for MSCs injections were osteoarthritis of the hip and knee (37.6%) and spinal cord injuries (10.5%). The most frequent sources of MSCs were bone marrow (26.5%), adipose-derived (20.5%) and umbilical cord (15.4%). Reported MSCs concentrations varied widely, ranging from 0.5 × 10⁶ to 9.7 × 10⁸ cells. The most frequently used concentrations were 1 × 10⁷ (8.2%), 2 × 10⁷ (8.0%), 5 × 10⁷ (5.8%), and 10 × 10⁷ (5.8%) cells, while 59 other dosing schemes were each used in fewer than 1% of trials. Furthermore, 55.5% of protocols did not specify the cell concentration. A search in PROSPERO identified 114 systematic review protocols. By the time of the study, 32 studies (28.10%) had been completed, with the results of 30 (26.32%) published in peer-reviewed journals. CONCLUSION: MSC injections represent a growing area of research in traumatology and orthopaedics. However, the results of only a small proportion of clinical trials and systematic reviews are published in peer-reviewed journals, which most likely does not allow practitioners to form a full judgement on the efficacy and safety of this treatment.

Objective: evaluation of the feasibility of using the Borg CR10 perceived exertion scale in the training process of young football players and its role in injury prevention. Material and methods: 48 athletes aged 15–17 were examined by scale of perceived exertion during the 7 month every day within 20 minutes after the training. The coaches also assessed the degree of perceived exertion. A comparative retrospective analysis of injuries was done for the periods of the mycrocycle of the youth football league of the seasons 2020–2021 and 2021–2022 based on muscle injuries, ligament and joint capsular injuries. Results: Athletes’ scores on the Borg CR10 scale in the preparation, competition and transitional stages of the competitive macrocycle are 5.08 ± 1.28, 5.00 ± 1.16 and 4.67 ± 1.38, respectively. The coaches’ scores for the aforementioned periods are 4.78 ± 0.89, 5.09 ± 1.05 and 4.82 ± 0.99. The total scores of players and coaches is 5.20 ± 1.85 and 4.96 ± 1 respectively. Moreover, there is no statistically significant difference between the rate of perceived exertion between players and coaches for the whole season (p = 0.288). There is a decreased injury rate in young professional athletes group when the Borg CR10 scale of perceived exertion is measured in a season with the use of this scale compared to a season where the Borg CR 10 scale was not used (p = 0,028). Conclusion: the Borg СR10 scale is a useful methodology for assessing the level of perceived exertion of a young athlete and can be used for early training corrections in order to reduce injuries.

The article provides findings of analytical research into the process of milling friable matter in a ball mill. We have received an expression to determine energy cost of milling with the account of the method of milling and the characteristics of the material to be ground. In the paper, the analytical results of bulk materials grinding process in a ball mill are presented. The differential equation is obtained whose solution determines the value of the grinding mode coefficient, corresponding to the maximum value of grinding process efficiency. The use of the introduced ball mill modes allows reducing the time spent on grinding by 28.9 % for cement clinker, 18.4 % for black coal, 28.9 % for marble and 19.6 % for rock salt compared to the traditionally recommended ones.