Vol 10, No 4 (2022)


Evaluation of plant-based UV filters potential in modern concept view of skin photoprotection

Nemyatykh O.D., Terninko I.I., Sabitov A.S., Lyashko A.I., Sakipova Z.B.


A therapeutic plants potential is based on the pharmacological effects due to their phytochemical profile. Today, scientific interest in botanicals is increasing as a result of recent research that looks at the prospect of using these raw materials for the cosmetic industry as a means to protect the skin from the harmful effects of UV rays.

The aim of the study was to evaluate a potential of plant-based UV-filters in modern concept view of skin photoprotection.

Materials and methods. A systematic literature search was carried out using the electronic information arrays PubMed, Scopus, Google Scholar, eLibrary. The search depth was 10 years (the period from 2010 to 2021). The search was carried out by the following keywords: antioxidants, cosmetics, photoprotection, chemical composition, pharmacological action.

Results. In the paper, modern principles of skin photoprotection based on the use of chemical or physical UV-filters are considered and scientifically substantiated A trend for the use of plant-based materials and their components in the formulation of photoprotectors was notified. That is associated with a wide activity spectrum, the absence of a xenobiotic effect, and a high bioavailability of organic plant compounds.

Conclusion. The data analysis from scientific publications demonstrated a potential photoprotective activity of plant-based biologically active substances due to antioxidant, anti-inflammatory and anti-radical effects. The results of the study are a theoretical basis for a further comprehensive experimental study of plant objects in order to obtain a pool of evidence in the field of photoprotection in in vivo experiments.

Pharmacy & Pharmacology. 2022;10(4):308-319
pages 308-319 views

Development of microcapsules based on combined antidiabetic substance: pharmacological characteristics

Giyoszoda A., Stepanova E.F., Veselova O.F., Storozhenko S.E.


The comparative assessment results of the hypoglycemic activity of a combined preparation containing microcapsules with a phytocomposition consisting of Glycyrrhiza glabra L. extracts, a dry extract of Galega officinalis L., Mentha piperita L., and gliclazide, are discussed in the article. Methods for obtaining microcapsules with an original PEG-6000 shell are described.

The aim of the study was to develop an optimal technology for obtaining microcapsules with a PEG-6000 shell containing a combined antidiabetic substance, and conduct its detailed pharmacological study on the model of type 2 diabetes mellitus, to conduct a detailed comparative pharmacological study of a microencapsulated antidiabetic composition with a shell based on PEG-6000, including gliclazide and a sum of phytoextracts on the model of type 2 diabetes mellitus.

Materials and methods. As the main objects of the study, microcapsules with a PEG-6000 shell were obtained using methyl miristate as the base liquid. The capsules contained the amount of plant extracts in their composition: a dry extract of Glycyrrhiza glabra L., a dry extract of Galega officinalis L., a dry extract of Mentha piperita L., and gliclazide. The study of a hypoglycemic activity was carried out after a single administration of drugs to the animals with alloxan-induced type 2 diabetes mellitus. The cumulative effect assessment of the drugs was carried out within 14 days with a test for the resistance to oral glucose on days 7 and 14.

Results. Microcapsules with the original shell were obtained by dispersion in a liquid-liquid system with the adjustment of some technological stages. The effect of the drugs under study on the glycemic profile in the rats with an experimental model of type 2 diabetes mellitus was investigated. A comparative evaluation of the pharmacological effect was carried out with a separate and combined use of microencapsulated preparations.

Conclusion. The rationality of combining phytocomponents and a synthetic antidiabetic agent in microcapsules has been proven. The obtained results testify to the rationality of plant extracts combination and a synthetic hypoglycemic agent – gliclazide in microcapsules.

Pharmacy & Pharmacology. 2022;10(4):320-330
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Adaptation of “dried blood drop” method for therapeutic drug monitoring

Petrov V.I., Anikeev I.S., Zayachnikova T.E., Strygin A.V., Dotsenko A.M.


To control the concentration of drugs with a narrow therapeutic range, and to conduct effective and safe treatments, Therapeutic Drug Monitoring (TDM) is carried out. However, to date, the implementation of TDM is associated with various difficulties, for the solution of which more convenient and less invasive methods for collecting biological material are being developed.

The aim of the study was to develop protocols for the collection and storage of “dried blood spot” (DBS) samples, as well as protocols for the validation methods for the quantitative determination of drugs in whole blood, using this technology for subsequent therapeutic drug monitoring.

Materials and methods. To analyze a “dried blood spot” method in detail and to identify the characteristic features of taking and storing biosamples, a collection and analysis of scientific literature over the past 10 years has been conducted. The search for literature materials has been carried out from open and accessible sources located in the scientific libraries of institutions, in electronic databases and search engines: Elibrary, PubMed, Scopus, Cyberleninka, Medline, ScienceDirect, Web of Science, Google Scholar. Primary protocols for taking, storing and analyzing samples of the “dried blood drop” have been prepared. To obtain the adequate quality samples, the developed protocols have been tested and optimized at the stages of selection and storage. By high-performance liquid chromatography with mass spectrometric detection (HPLC-MS/MS), using a “dried blood drop” as a sample preparation, drug validation protocols have been optimized to ensure that acceptable validation characteristics were achieved, and subsequent Therapeutic Drug Monitoring was performed.

Results. The features of the collection, storage and analysis of the “dried blood spot” samples have been revealed. Such characteristics as a spot volume effect, a hematocrit effect, a droplet uniformity, which can affect the results of a quantitative HPLC-MS/MS analysis, have been determined. For a successful use of the new methods, appropriate protocols for taking samples of “dried blood spot” from the finger of adult patients and from the heel of newborns, as well as protocols for validating methods for the quantitative determination of drugs from these samples, have been developed.

Conclusion. The application of the “dried blood spot” method using newly developed protocols for taking, storing and analyzing biological samples, relieves the existing constraints in conducting TDM, and can later become a promising method for conducting preclinical and clinical studies.

Pharmacy & Pharmacology. 2022;10(4):331-342
pages 331-342 views

Interrelation between mitochondrial enzyme activity and antioxidant activity of secondary polyphenol nature metabolites in hemiparasite Viscum album L. leaves

Adzhiakhmetova S.L., Pozdnyakov D.I., Chervonnaya N.M., Kulichenko E.O., Oganesyan E.T.


Antioxidants are widely used in practical medicine. Not only the search for new plant antioxidants, but also the study of the factors affecting their accumulation in plants, are relevant.

The aim is to study the interrelation between the activity of mitochondrial enzymes and the antioxidant activity of the secondary polyphenolic nature metabolites in hemiparasite Viscum Album L. leaves.

Materials and methods. The sampling material was Viscum album L. leaves, collected in winter from a host tree, Malus domestica Borkh. The extraction of biologically active substances was carried out with ethyl alcohol of various concentrations (90%, 70% and 50%), or purified water. The amount of total antioxidants was estimated by the amperometric method. The amount of total phenols was evaluated in the reaction with the Folin-Ciocalteu reagent. The concentration of total flavonoids was estimated by the change in the optical density of the rutin with aluminum (III) chloride complex. The antioxidant properties of the analyzed extracts were determined in vitro in the induced lipid peroxidation test. The activity of aconitase was assessed by a conjugated aconitase-isocitrate dehydrogenase reaction, citrate synthase – by changing the color intensity of the Ellman reagent solution, succinate dehydrogenase were determined in the reaction of succinate-dependent oxidation of 2,6-dichlorophenolindophenol.

Results. The carried out study showed that the maximum amount of total phenols (2.39±0.05%) is observed in a 50% ethanol extract from Viscum album L. leaves, with the content of total flavonoids equal to 1.83±0.04%, and the antioxidants equal to 0.503±0.007 mg/g (a quercetin equivalent) and 0.322±0.006 mg/g (a gallic acid equivalent). A 50% ethanol extract suppressed lipid peroxidation in the model mixture with IC50=106.3±1.09 µg/ml. In Viscum album L. leaves, a high activity of aconitase which strongly correlated (r=0.88416) with changes in the concentration of flavonoids, has been notified.

Conclusion. The optimal extractant for obtaining extracts with a high antioxidant activity is 50% ethyl alcohol. The analysis of the mitochondrial enzymes activity showed that in Viscum album L. leaves collected in winter, a high activity of aconitase strongly correlated with changes in the concentration of flavonoids (r=0.88416).

Pharmacy & Pharmacology. 2022;10(4):343-353
pages 343-353 views

Safety study of romiplostim biosimilar

Afanasyeva A.N., Saparova V.B., Karal-Ogly J.J., Mukhametzyanova E.I., Kurkin D.V., Kalatanova A.V., Makarenko I.E., Khokhlov A.L., Lugovik I.A.


Idiopathic thrombocytopenic purpura is a chronic autoimmune hematological disease caused by an increased destruction of platelets and associated thrombocytopenia, for the treatment of which the imported drug romiplostim is used. Сreation of the drug biosimilar provides a reduction in the cost of therapy and an access for the treatment to more patients.

The aim of the study was to compare the safety indicators of the reference drug and its biosimilar in vivo and in vitro.

Materials and methods. In the in vitro study, a model of “complement-dependent cytotoxicity” induced by the complement was formed on the 32D hTPOR clone 63-cell line, followed by a cell viability measurement with the CellTitter Glo® kit. An in vivo part of the study was carried out on Javanese macaque monkeys (Macaca fascicularis). During the experiment, the clinical condition, mortality, appetite of the animals, their body weight, body temperature, respiratory rate were assessed, the clinical parameters of blood and urine of the animals were also monitored, and the hemostasis indicators were additionally measured.

Results. In the in vitro experiment, the original drug romiplostim and its biosimilar GP40141 were compared in terms of EC50 values. The indicatirs did not show complement-dependent cytotoxicity. According to the in vivo results, no deviations were recorded in the clinical status of the animals and their feed intake, and no lethality was fixed out in the groups either. For all the parameters studied (body weight and temperature, respiratory rate, clinical urinalysis, clinical and biochemical blood tests, coagulation hemostasis), GP40141 and romiplostim, when administered at the doses equivalent to 10 toxic doses (TDs), had comparable effects.

Conclusion. In the comparison of safety performance both in vitro and in vivo, the original drug romiplostim and its biosimilar GP40141 showed similar results.

Pharmacy & Pharmacology. 2022;10(4):354-370
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Modern directed antiviral COVID-19 therapy: results of multicenter clinical effectiveness and safety study of fixed nirmatrelvir+ritonavir combination

Balykova L.A., Selezneva N.M., Gorshenina E.I., Shepeleva O.I., Kirichenko N.V., Simakina E.N., Kolontarev K.B., Pushkar D.Y., Zemskov D.N., Zaslavskaya K.Y., Noskov S.M., Taganov A.V., Bely P.A.


The article presents the data from an open, two-stage, multicenter study on the efficacy and safety evaluation of a combined drug (a fixed combination of nirmatrelvir 300 mg, and ritonavir 100 mg) in the complex therapy in COVID-19 patients.

The aim of the study was to assess the safety, tolerability and pharmacokinetic parameters of the fixed combination of nirmatrelvir 300 mg and ritonavir 100 mg in healthy volunteers, the efficacy and safety assessment of the drug in the combination therapy compared with the standard therapy in COVID-19 patients.

Material and methods. An open two-stage multicenter clinical study to assess the main pharmacokinetic parameters, safety, and efficacy against COVID-19 of the drug nirmatrelvir 300 mg and ritonavir 100 mg combination (Skyvira® PROMOMED RUS LLC, Russia) in the adult population, included 2 stages. At stage 1, safety, tolerability and pharmacokinetic parameters were evaluated in healthy volunteers (over 18 years of age) in order to confirm their comparability with the literature data known for a set of active substances. Phase 2 assessed efficacy and safety in COVID-19 patients. As a part of the second stage, the study involved 264 patients (men and women aged 18 to 80 years), who had been divided into two groups. The first group patients (n=132) received the study drugs (nirmatrelvir 300 mg and ritonavir 100 mg) – 1 tablet twice a day with an interval of 12±2 hours for 5 days in combination with pathogenetic and symptomatic therapy. The second group patients (n=132) received standard therapy in accordance with the approved Temporary Guidelines for the Prevention and Treatment of Novel Coronavirus Infection (Version 15 dated February 22, 2022).

Results. During the study, none of the patients from the (nirmatrelvir + ritonavir) group experienced a transition of the COVID-19 course to a heavier severity level, in contrast to the patients in the standard therapy group. The study participants included patients with comorbidities (68% of the general population), with risk factors for COVID-19 progression to a heavier severity level and the risk of hospitalization (75% of the general population). There were no cases of COVID-19 progression to a heavier severity level in the study drug group. By the 6th day, in the nirmatrelvir + ritonavir group, the proportion of the patients who had achieved a complete recovery was twice more and amounted to 35.61% (p=0.0001), and the proportion of the patients with a negative RNA analysis to SARS-CoV-2 was 20% higher than in the comparison group, and amounted to 82.58% (p=0.0001). The fixed nirmatrelvir + ritonavir combination therapy has a favorable safety profile comparable to the standard therapy. The identified adverse reactions were transient in nature and did not require discontinuation of therapy or changes in the treatment regimen.

Conclusion. The fixed nirmatrelvir + ritonavir combination has a favorable safety profile in COVID-19 patients, comparable to the standard therapy. The data obtained demonstrate a clinical and pharmacoeconomic feasibility of including the fixed (nirmatrelvir + ritonavir) combination in the COVID-19 treatment regimen.

Pharmacy & Pharmacology. 2022;10(4):371-386
pages 371-386 views

Synergic effect of preparation with coordination complex “trimethydrazinium propionate+ethymth methylhydroxypiridine succinate” on energy metabolism and cell respiration

Zhuravleva M.V., Granovskaya M.V., Zaslavskaya K.Y., Kazaishvili Y.G., Scherbakova V.S., Andreev-Andrievskiy A.A., Pozdnyakov D.I., Vyssokikh M.Y.


The article presents the results of an in vitro study of the synergetic effect evaluation of the combined preparation based on coordination complex ethylmethylhydroxypyridine succinate and trimethylhydrazinium propionate on energy metabolism and cell respiration.

The aim of the study was to evaluate the mitochondria-directed action of the metabolic and antioxidant preparation based on succinic acid coordination complex with trimethylhydrazinium in relation to optimizing the energy metabolism in the cells under the oxidative stress conditions, as well as against the background of ischemic processes.

Materials and methods. The study of the hydroxysuccinate complex effect of the drug Brainmax® components was carried out on isolated mouse liver mitochondria. In the course of the study, the potential of mitochondria, the generation rate of hydrogen peroxide during the respiration, the respiration rate were evaluated in the following positions: a) unstimulated by malate and pyruvate, b) stimulated by malate and pyruvate (complex I substrates), by succinate (complex II substrates), c) against the background of the initial section of the electron transport chain blockade by rotenone, d) in phosphorylation blockade by oligomycin, e) against the background of the FCCP-induced uncoupling, and f) in cyanide-blocked complex IV (cytochrome C oxidase).

Results. It has been shown that the succinic acid coordination complex with trimethylhydrazinium, which is the active principle of the Brainmax® drug, significantly reduced the transmembrane potential of mitochondria (IC50=197±5 µM), compared with the widely used preparations of ethylmethylhydroxypyridine succinate and trimethylhydrazinium propionate, which facilitates the transfer of the produced ATP into the cell and preserves a vital activity of mitochondria even under stress. In the study of the mitochondrial respiration stimulated by the substrates of complex I (NADP-coenzyme Q-oxidoreductase), pyruvate and malate, the studied drug led to a more pronounced increase in the oxygen consumption with IC50=75±6 µМ. When evaluating the effect of the complex on the production of ATP by mitochondria, the most pronounced effect was observed with the addition of studied complex, which indicated to the uncoupling of respiration and oxidative phosphorylation at the given concentrations of the studied compounds. When assessing the effect of the complex on the production of hydrogen peroxide by isolated mitochondria, a significant decrease in the peroxide production was shown in the samples containing the complex of trimethylhydrazinium propionate and EMHPS.

Conclusion. Based on totality of the results obtained, it can be assumed that a favorable conformation of the pharmacophore groups of ethylmethylhydroxypyridine succinate and trimethylhydrozinium propionate coordination complex included in the composition of Brainmax® leads to a synergetic interaction and more pronounced pharmacological effects on target cells. This complex provides stabilization of a mitochondrial function, intensification of the adenosine triphosphate energy production and the optimization of energy processes in the cell, reduces the severity of the oxidative stress and eliminates undesirable effects of an ischemic-hypoxic tissue damage.

Pharmacy & Pharmacology. 2022;10(4):387-399
pages 387-399 views

Corrigendum: “Evaluation of weight reduction efficacy and safety of sibutramin-containing drugs in patients with alimentary obesity”

Demidova T.Y., Izmailova M.Y., Ushakova S.E., Zaslavskaya K.Y., Odegova A.A., Popova V.V., Nevretdinova M.E., Verbovoy A.F., Bely P.A.
Pharmacy & Pharmacology. 2022;10(4):400-400
pages 400-400 views

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