Vol 6, No 6 (2018)



Nikitina A.S., Logvinenko L.A., Nikitina N.V., Nigaryan S.A.


The article presents the results of morphological-anatomical, morphometric and histochemical studies of the aerial part of Melissa officinalis L., a selection variety sample from the collection of Nikitsky Botanical Garden – National Science Center (NBG-NSC) of the Russian Academy of Sciences, Republic of Crimea. The data on the morphology, histochemistry and morphometry of the main diagnostic microscopic signs of the Melissa officinalis L. herb, which are crucial for establishing the authenticity of medicinal plant materials, and also show the localization of secretion of metabolites and the heterogeneous nature of Melissa essential oil, have been obtained.The aim. Is to determine the microdiagnostic signs and biometric characteristics of the Melissa officinalis L. variety sample, introduced in Nikitsky Botanical Garden, to study the possibility of using histochemical reactions for the analysis of tissues and secretory structures of the studied species.Materials and methods. The plant material was provided by Nikitsky Botanical Garden. The study of microscopic signs, morphometric characteristics as well as histochemical tests, were performed according to the methods of the State Pharmacopoeia of the Russian Federation, XIII edition, using a Micromed-1 light microscope, a Micromed Micrometer 3 LUM fluorescent microscope and a Digital Eyepiece microscope camera MD 3.2 digital camera. The photos were edited in the program Paint. NET.3.5.11.Results. The main diagnostic microscopic signs of the herb of the Melissa officinalis L. selection variety sample can be called as follows: simple unicellular conical, nonbranching hairs, simple multicellular conical hairs, capitate hairs with a multicellular leg and a funnel-shaped head and with a unicellular leg and a spherical head, essential oil glands of a radial-type with 6-8 excretory cells. These signs have been diagnosed in the crushed raw materials. A quantitative assessment of the morphological and anatomical signs of the leaf (leaf thickness, height of the cells of the upper and lower epidermis, stoma density per 1 mm2 of the epidermis), stem, calyx and corolla was carried out. The size of cells, stoma, trichomes, as well as the frequency of the location of trichomes have been analyzed, too. The presence and localization of lipids, polysaccharides, phenolic compounds, flavonoids, essential oil, terpenoids, alkaloids in tissues and trichomes of the herb have been studied by histochemical methods using light and fluorescent microscopy.Conclusion. Morphological and anatomical study of the herb of the Melissa officinalis L. selection variety sample from the Nikitsky Botanical Garden collection has been carried out, diagnostically significant microscopic signs of raw materials have been revealed and their biometric characteristics have been established. For the first time the localization of characteristic secreted biologically active substances in the tissues and secretory structures of the herb has been studied by histochemical methods. The results of the experimental studies complement the scientific literature data and can be used to confirm the authenticity, identification and standardization of the aerial parts of this variety sample.
Pharmacy & Pharmacology. 2018;6(6):504-534
pages 504-534 views


Alexeeva K.A., Pisarev D.I., Malyutina A.Y., Boyko N.N.


Glutathione (γ-L-glutamyl-L-cysteinylglycine) is the most important low molecular weight intracellular thiol tripeptide consisting of three amino acids – glycine, cysteine and glutamic acid. In Russian pharmacopoeia there is no regulatory documentation for glutathione, therefore, the development of a pharmacopoeial item for the specified substance is a relevant problem.The aim of the article is the development of methods for determining foreign specific impurities in glutathione.Materials and methods. The substance of glutathione reduced (CAS 70-18-8, EC 2007254, Applichem, Germany) containing impurities, and a standard sample of reduced glutathione (Sigma Aldrich, Japan) were used as the objects of the study. The analysis was carried out by using a high-performance liquid chromatography method in the reverse phase version and a thin layer chromatography method. The chromatography using RP HPLC was performed after preliminary derivatization of glutathione and its specific impurities with dancil chloride. Specific impurities in glutathione are dipeptides and amino acids. Therefore, they, like glutathione, can react with dancil chloride. Dancil derivatives are formed, and they can be determined by chromatographic separation.Results. As a result of chromatography by the method of RP HPLC of derivatized dancil chloride glutathione it has been established that this reaction makes it possible to detect impurities in it. Glutathione derivatives are well separated by chromatography by implementing the method of RP HPLC and have different absorption maxima. The glutathione derivative had an absorption maximum at λmax=284 nm. The derivatives belonging to specific glutathione impurities absorb at λmax=288 nm and λmax=296 nm. The data obtained using RP HPLC were confirmed by TLC in the isopropanol-water (2:1) system. Three components were found out, one of which corresponds to glutathione, while two others are impurities.Conclusion. Methods for determining impurities in the glutathione substance using RP HPLC methods with preliminary derivatization with dancil chloride and TLC with ninhydrin detection have been worked out. A comparative analysis of the data obtained makes it possible to state that the OF-HPLC method with pre-column derivatization is more reliable, since it is more sensitive to impurities, and also makes it possible to study the UV profiles of impurity components better than the TLC method. Therefore, for the detection of impurities in the substance of glutathione, it is more preferable to use RP-HPLC with pre-column derivatization. The results of this study can be recommended for inclusion in the regulatory documentation on the substance of glutathione in the section “Impurities”.
Pharmacy & Pharmacology. 2018;6(6):535-547
pages 535-547 views


Voronkov A.V., Shabanova N.B., Voronkova M.P., Lysenko T.A.


Nowadays, the incidence of cerebrovascular disease is steadily increasing. Disorders of cerebral circulation contribute to the increase in the degree of mortality, disability, and incapacitation of the population. An extensive arsenal of drugs with cerebroprotective effects does not satisfy clinical specialists. In this connection, there is an obvious need for new compounds exhibiting cerebroprotropic properties, as well as those able of improving the prognosis of the course of ischemic genesis pathologies.The aim of the article is to study the dose-dependent cerebrotropic effect of a pyrimidine derivative under PIR-9 code against the background of experimental cerebral ischemia in rats.Materials and methods. The experiment was conducted on 140 male Wistar rats (m=170–190 g) divided into 7 equal groups. Pyrimidine derivative PIR – 9 (25, 50 and 100 mg/kg), Vinpocetine (3.2 mg/kg) and Cinnarizine (5.6 mg/kg) suspension of purified water and Tween-80 were used as the studied substances. Experimental cerebral ischemia was reproduced by irreversible occlusion of common carotid arteries (chloral hydrate anesthesia – 350 mg/kg). Experimental substances, reference preparations and purified water were administered prophylactically within 10 days before surgery. One day later the survival, neurological deficiency, behavioral activity, changes in cognitive-mnestic functions, as well as some indicators of brain energy exchange were evaluated.Results. In an experimental study of the cerebrotropic effect of the substance under PIR-9 code (pyrimidine-4-(1H)-one derivative) in various dosages against the background of irreversible occlusion of the common carotid arteries, a decrease in neurological, behavioral, mnestic and cognitive defects has been established. Hereby, the best effect was observed against the background of the administration of the compound PIR-9 at the dose of 50 mg kg. In addition, the prophylactic administration of the test substance PIR-9 (50 mg/kg) has shown the improvement of the energy metabolism in the postischemic period.Conclusion. In the course of the study it was established that the substance under the laboratory code PIR-9 exhibited the most pronounced cerebroprotective effect at the dose of 50 mg/ kg, which was not inferior in its strength to the reference drug Cinnarizine and exceeding Vinpocetine.
Pharmacy & Pharmacology. 2018;6(6):548-567
pages 548-567 views


Matveev A.V., Krasheninnikov A.Е., Egorova E.A., Konyaeva E.I.


According to the data of the World Health Organization (WHO), human immunodeficiency virus (HIV) remains a major global public health problem.The main method of treating HIV is using highly active antiretroviral therapy (HAART), which is the use of multiple medicines acting on different viral targets. The timely onset of HAART can suppress the replication of the virus in the human body and helps to strengthen its immune system and restore its ability to fight infections. At the same time, the choice of medicines to improve the quality of life and patients’ compliance during antiretroviral therapy should be based on their effectiveness and safety. The aim of this research was to analyze and study the adverse reactions that occur in patients with HIV living in the territory of the Republic of Crimea, when using HAART.Materials and methods. The objects of research were 274 report cards about the adverse reactions, registered in the regional base (registry) of spontaneous messages called ARCADe (Adverse Reactions in Crimea, Autonomic Database) for the period from 2011 to 2016.Results. The results of the study showed that the most often adverse reactions were observed when using medicines of the group of Nucleoside Reverse Transcriptase Inhibitors (NRTI). This is explained by the inclusion of NRTI medicines as the main medicine in the method of HAART. Efavirenz (EFV) and Nevirapine (NVP) were absolute leaders among these groups of antiretroviral medicines. Among the combined antiviral medicines active against HIV, the most frequently adverse reactions were associated with the use of a combination of Lamivudine (3TC) and Zidovudine (ZDV). The main clinical manifestations of adverse reactions in the use of combination medicines for treating HIV were a decrease in the level of hemoglobin and the development of anemia. At the same time, in 85% of cases, the patients needed medication in order to correct the resulting adverse drug reaction (ADR). The combination of antiretroviral therapy has often been associated with the development of serious ADR. In case of monotherapy, the main clinical manifestations of adverse reactions were disorders of the central nervous system (dizziness, hallucinations, sleep disorders) and allergic reactions of varying severity (including 1 case of angioedema to “Eferven” (Efavirenz (EFV)),600 mg). Hereby, in almost half of the cases, the usage of antiretroviral medicines of the NRTI group and protease inhibitors caused the development of serious side effects. This confirms the necessity to study and analyze adverse reactions in order to increase the safety of patients’ pharmacotherapy and improve their quality of life.Conclusion. The study of adverse reactions to the medicines used for treatment of HIV is of a paramount importance in improving the safety and compliance of HIV patients to lifelong pharmacotherapy.
Pharmacy & Pharmacology. 2018;6(6):568-583
pages 568-583 views


Krasheninnikov A.Е.


The aim of this article is to  systematize the known data based on facts relating to the formation of the global pharmacovigilance system, and its further use for the periodization  development of the selected social institution.Materials and methods. The development of the periodization of the historical development of the world pharmacovigilance system was carried out using the systematic, epistemological, historical descriptive methods, as well as using the method of generalization.Results. The results of the study made it possible to identify a number of stages in the global development and institutionalization of pharmacovigilance.Conclusion. The carried out research confirmed that the aggregate approach applied to the global genesis of the world pharmacovigilance system is an effective scientific and methodological technique that contributes to the development of a new level of application and systematization of knowledge about pharmacovigilance as a complex institution, conglomerating in-house science and practical interstate activity.
Pharmacy & Pharmacology. 2018;6(6):584-589
pages 584-589 views

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