Рharmaceutical practice of advanced regulatory healthcare systems places high demands on the quality and safety of medicines, especially on compounding drugs by pharmacies. The United Kingdom is one of the countries with a developed system of legal regulation of drug treatment, which is based on the principles of effective management and is aimed not only at following formal procedures, but also at ensuring the ultimate goals, namely patient safety, quality of manufactured drugs and effectiveness of pharmaceutical processes.

The aim. To identify the key elements of the British system of regulation of drugs compounding by pharmacies, to assess their applicability in other legal systems and to form promising directions for improving Russian legislation.

Materials and methods. The study based on analysis of the UK regulatory framework governing circulation of medicines, as well as documents from government agencies and regulatory agencies. Comparative legal, content analysis, a systematic approach, analytical and empirical methods were used.

Results. Pharmaceutical activity is regulated by the General Pharmaceutical Council, which develops standards and guidelines that are binding. The production of medicines is carried out within the framework of a licensing system and is subject to the principles of good practices. The British system is based on a model of effective regulation, where the emphasis is on achieving targeted results rather than strictly following procedures. There is a separate license for the production of special drugs designed for a specific patient.

Conclusion. Legal and regulatory systems for manufacturing of medicines in the UK demonstrates high degree of harmonization with international standards, including GMP and PIC/S recommendations. It can serve as a model for improving legislation in other countries, including the Russian Federation, in terms of developing and implementing a unified system of regulatory support for manufacturing of medicines, including introduction of adapted GMP requirements into of pharmaceutical medicine manufacturing practice — good practices for the preparation of medicinal products.

The aim. To analyze and summarize the available results of experimental and clinical scientific studies of synthetic analogs of leu-enkephalin; to evaluate the expansion of the spectrum of application of the original medicine based on hexapeptide succinate in patients with various diseases of different etiologies.

Materials and methods. An analysis of scientific literature data in the PubMed, eLibrary.ru and CyberLeninka databases was carried out. The search depth was 50 years (from 1976 to 2024), the list of references includes 60 scientific papers.

Results. It was revealed that receptors for endogenous opioid peptides are widespread in living organisms. Modern neuropharmacology recognizes 4 main types of opioid receptors: μ (MOR) — mu, δ (DOR) — delta, κ (KOR) — kappa and NOP — nociceptive receptor, which bind to endogenous opioids such as enkephalins, endorphins, endomorphins, dynorphins and nociceptin. Due to their antioxidant, immunomodulatory, and anti-inflammatory properties, analogs of opioid peptides are widely used in Russian medicine. A number of experimental and clinical studies are presented, to prove that agonists of delta-opioid receptors can “soften” organ damage in a variety of diseases accompanied by oxidative stress and endothelial dysfunction. The dose-dependent regulatory effect is realized with intravenous, intramuscular and intranasal administration. The therapeutic efficacy of leu-enkephalin analogs based on tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine is analyzed, and the prospects for using the new original Russian medicine Ambervin® Pulmo with the inclusion of succinic acid salts are also discussed.

Conclusion. The information on the functional properties of leucine-enkephalin analogs presented in the article indicates broad prospects for the use of medicines based on tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine with the inclusion of succinic acid salt in the complex therapy of many diseases for the purpose of organ protection.

 The aim. To identify existing obstacles hindering the introduction of extemporaneous orphan drugs into circulation in the Russian Federation, in order to develop recommendations for improving legislative regulation and organizing the activities of pharmacies with the right to manufacture drugs.

Materials and methods. The study was performed using a comprehensive approach, including logical, comparative, structural-functional, and conceptual analysis. Information retrieval was conducted in international scientific indexes, search engines (PubMed, Google Scholar), and legal reference systems (ConsultantPlus, GARANT, Kontur.Normativ). Regulatory legal acts of the Russian Federation and foreign countries, modern scientific publications, as well as the practical experience of Russian pharmacies manufacturing drugs for the treatment of orphan diseases were considered.

Results. The main obstacles in the development of pharmacy compounding of orphan drugs were identified: low availability of active pharmaceutical ingredients, limitation of the mechanism for establishing the shelf life of extemporaneous dosage forms, prohibition of the manufacture of registered drugs, heterogeneity of pharmacies in terms of equipment and competencies, lack of stable demand, restriction of dispensing compounded drugs for outpatient treatment, and uncertainty of requirements for the therapeutic effectiveness of extemporaneusly compounded drugs. Based on the analysis, proposals were formulated to improve the regulation of mechanisms for admitting substances to the market, using flexible approaches to establishing shelf life, differentiating requirements for pharmacies depending on their capabilities, and legally establishing the rights to manufacture certain categories of drugs, simplifying the dispensing of extemporaneous dosage forms, and involving federal and regional institutions in the formation of stable demand for pharmacy drugs.

Conclusion. Overcoming the identified obstacles is of strategic importance not only for the pharmacotherapy of orphan diseases, but also for the development of pharmacy compounding in general. The implementation of the proposed solutions will create a sustainable system capable of providing patients with vital medicines regardless of market conditions and the political situation. Global practice confirms that key competition in the field of orphan drugs unfolds precisely at the level of regulatory systems, and in this perspective, the development of manufacturing pharmacies can become a tool for the Russian Federation to protect the interests of patients, increase access to therapy, and strengthen drug sovereignty.

The aim. Pharmacognostic study of wild carrot fruits: identification of the main microscopic features; chromatographic-mass spectrometric study of volatile compounds and determination of numerical commodity indicators of medicinal plant raw materials.

Materials and methods. Morphological and anatomical features of wild carrot root raw materials were studied by light microscopy; luminescence of tissues and working standard samples of substances were studied by luminescent microscopy; crystalline structures were studied by polarization microscopy; the profile of volatile compounds in raw materials was assessed using chromatographic-mass spectrometry. The preparation of microscopic slides, the determination of numerical commodity indicators of medicinal plant raw materials were carried out according to the requirements of the State Pharmacopoeia of the Russian Federation XV edition.

Results. Morphological and anatomical analysis established the characteristics of carrot fruits: oval shape of the fruit, tapering towards the apex, brown in color with seven veins; schizogenous containers of angular shape with non-cellular septa; endosperm parenchyma of isodiametric, oval cells; endocarp of parquet type from elongated, thick-walled, tightly closed cells; stellate druses in the tissues of the embryo with four symmetrical rays. Luminescence in the excitation range of 330–400 nm of the mesocarp — bright blue; epithelial cells — light yellow; resinous secretion — blue; chromatographic-mass spectrometric study of hexane and chloroform fractions of the extract from carrot fruits determined the profile of volatile compounds, with carotol being predominant (25.9% and 30.1%, respectively).

Conclusion. The identified microscopic features, the main biologically active substance, and numerical commodity indicators are of practical importance for inclusion in the draft pharmacopoeial monograph “Wild Carrot Fruits”.

The aim. To evaluate the antiviral efficacy of ASD drug on a model of lethal influenza pneumonia in mice against influenza A viruses of subtypes H3N2, H5N2 and H5N8.

Materials and methods. Balb/c mice were infected with influenza viruses. The decrease of mortality and improvement in the weight dynamics of infected animals (15 animals per group) were evaluated, and the viral load in the lung tissue was determined on day 3 after infection (6 animals per group). Oseltamivir was used as a comparator medicine, and placebo was administered to negative control group animals. The medicines were administered according to a therapeutic-prophylactic or therapeutic regimen.

Results. The maximum weight loss with the H5N8 virus infected mice (placebo group) was 16.8% on day 12 (therapeutic-prophylactic regimen) and 14.8% on day 9 (therapeutic regimen). ASD worsened the dynamics of weight loss, up to 21% on day 12 (therapeutic-prophylactic regimen) and up to 28.4% on day 9 (therapeutic regimen). The maximum weight loss with the H5N2 virus infected mice was 34.6% on day 8 (therapeutic-prophylactic regimen) and 31.2% on day 7 (therapeutic regimen). The ASD medicine reduced the dynamics of weight loss: up to 29.9% on day 8 (therapeutic-prophylactic regimen) and up to 26.3% on day 7 (therapeutic regimen). The maximum weight loss with the the H3N2 virus was 38.4% on day 11 (therapeutic-prophylactic regimen) and 33.9% on day 9 (therapeutic regimen). The ASD medicine improved the dynamics of weight loss to 18.5% on day 11 (therapeutic-prophylactic regimen), but with the therapeutic regimen, it worsened the dynamics to 34.1% on day 9. A decrease of the survival rate of mice infected with the H5N8 virus using ASD (therapeutic regimen) was revealed. Mice receiving ASD and infected with the H3N2 virus (therapeutic-prophylactic regimen) or H5N2 (therapeutic regimen) showed a tendency towards a protective effect of the drug. No effect of the ASD medicine on the level of viral load was noted.

Conclusion. The ASD medicine exhibits antiviral properties when administered orally according to a therapeutic-prophylactic regimen against influenza A virus (subtypes H3N2 and H5N2).

The aim. To study the quantitative characteristics of the implementation of drug provision for beneficiaries with diabetes mellitus (DM) in the Stavropol Region in the period from 2020 to 2024.

Materials and methods. The regulatory legal basis of the study was made up of legislative acts of the federal and regional levels on the organization of preferential drug provision (PDP). Clinical and epidemiological monitoring of DM was carried out according to the data of the State Register of DM for the Stavropol Region, data from the Regional Endocrinological Dispensary (Stavropol Region, Russia), as well as reports from executive authorities.

Results. According to the clinical and epidemiological monitoring of DM in the Russian Federation in 2024, the prevalence of DM in the Stavropol Region did not exceed the average Russian indicators (rating 36). A decrease in the number of federal beneficiaries and an increase in the number of regional beneficiaries (with a predominance of DM type II) was noted. 10 municipalities where about 60% of patients with DM live were identified. Therapy for patients with DM type I is based on insulin therapy for 100% of patients. Therapy for patients with DM type II includes the use of insulin for 14,140 (20.63%) patients, oral hypoglycemic agents for 53,404 (77.88%) patients, and dietary adjustments for 1,025 (1.49%) people. Since 2024, in accordance with changes in the legislation of the Stavropol Region, all patients with DM are provided from general funds of the regional budget, with the exception of federal beneficiaries in Lermontov, who are provided at the expense of the program for the provision of necessary medicines (PNMs). The structure of expenditures from the federal and regional budgets for the purchase of funds for the treatment of DM is presented. The dynamics of the growth of expenses per one beneficiary with DM is shown. It should be noted that in 2024 there was an equalization of the amount of expenses per one federal and regional beneficiary.

Conclusion. The results obtained can be used by other researchers to take solutions to improve the availability of drug provision for beneficiaries with DM both in the Stavropol Region and in other subjects of the Russian Federation.

The aim. To investigate the pharmacokinetic parameters of non-immunogenic staphylokinase (Fortelyzin®, SuperGene LLC, Russia) in patients with acute myocardial infarction with ST-segment elevation (STEMI) on the electrocardiogram and in patients with ischemic stroke.

Materials and methods. The clinical study was conducted in 50 patients with STEMI after a single intravenous administration of non-immunogenic staphylokinase at a dose of 15 mg and in 50 patients with ischemic stroke after a single intravenous administration of the drug at a dose of 10 mg. The main pharmacokinetic parameters were determined: half-life, initial concentration, volume of distribution, clearance, and area under the pharmacokinetic curve.

Results. As a result of the study of the pharmacokinetics of non-immunogenic staphylokinase, it was found that after a single intravenous administration of the drug at a dose of 15 mg, the initial concentration was 7.1 ± 2.7 μg/mL, the half-life was 5.77 ± 0.72 min, the clearance was 0.33 ± 0.04 l/min, and the area under the pharmacokinetic curve (AUC_0-t) was 42.9 ± 3.2 μg/mL*min. After administration of the drug at a dose of 10 mg, the initial concentration was 2.8 ± 0.3 μg/ml, the half-life was 5.11 ± 0.56 min, the clearance was 0.35 ± 0.06 l/min, and the area under the pharmacokinetic curve (AUC_0-t) was 28.5 ± 3.6 μg/mL*min. The terminal half-life was 32 min in both dosage regimens.

Conclusion. It was found that non-immunogenic staphylokinase is characterized by a short half-life and high clearance, which ensures the safety of the drug in clinical practice. The peculiarities of the pharmacodynamics of non-immunogenic staphylokinase, associated with its interaction with plasmin in the thrombus and subsequent recirculation of released drug molecules, allow it to be used in low doses, regardless of the patient’s body weight, despite the short half-life.