Vol 8, No 1 (2020)

Articles

MEMBERS OF THE FAMILY LAMIACEAE LINDL. AS SOURCES OF MEDICINAL PLANT RAW MATERIALS TO OBTAIN NEUROTROPIC DRUGS

Zvezdina E.V., Dayronas Z.V., Bochkareva I.I., Zilfikarov I.N., Babaeva E.Y., Ferubko E.V., Guseynova Z.A., Serebryanaya F.K., Kaibova S.R., Ibragimov T.A.

Abstract

The aim of this work is to review and analyze the data published in the modern scientific literature obtained in pharmacological, pharmacognostic and pharmacotechnological studies of various types of raw materials obtained from members of the family Lamiaceae L., which were sources of biologically active substances, pharmaceutical substances, total extracts and the drugs – with a neurotropic activity.

Materials and methods. For the review, we used the information of scientific literature from open and accessible sources of the last twenty years, located in the scientific and technical libraries of institutions, as well as in electronic databases: Elibrary, PubMed, Scopus, Cyberleninka, GoogleAcademy, J-Stage. The search inquiries were: the species of the family Lamiaceae (Russian and Latin), the samples of medicinal plant materials based on them as well as the names of the drugs and biologically active substances obtained from these raw materials.

Results. When working with the sources of scientific information, the main attention was paid to pharmacologic tests performed during the studies on laboratory animals and proving the presence of neurotropic activity in the studied objects – essential oils and extracts from plant raw materials: aqueous, aqueous alcoholic, and methanol ones. It has been established that the potential of the therapeutic and preventive application of pharmaceutical substances and drugs based on the medicinal plant materials obtained from 30 genera members of the Lamiaceae family, remains unrealized despite the close attention of various researchers.

Conclusion. This review comprised 71 species from 30 genera. Despite the significant level of the previous study presented in the analysis of this publication, an enormous potential of this family’s species remains unexplored. In the future, they can be of both – pharmacognostic and practical interest, in particular, in creation of new medicinal preparations of the neurotropic action based on them.

Pharmacy & Pharmacology. 2020;8(1):4-28
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RESULTS OF A COMPARATIVE STUDY OF NIGELLA SATIVA L. SEEDS OILS COMPOSITION

Goryainov S.V., Khromov A.V., Bakureza G., Cesar E., Ivlev V.A., Vorobyev A.N., Abramovich R.A., Potanina O.G., Novikov O.O.

Abstract

This article presents results of the chemical composition study of the seeds oils lipid complex of Nigella Sativa L. grown under various geographic conditions. The task of the comprehensive study of the chemical composition of the plant and its individual parts remains relevant due to the wide spectrum of its pharmacological activity.

The aim of this work is a comparative study of the fatty acid composition, a non-saponifiable fraction and the composition of essential oils of Nigella Sativa L. seeds grown in different regions of the world.

Materials and methods. The combination of chromatography-mass spectrometry and 1H-NMR spectroscopy methods made it possible to study the qualitative and quantitative composition of Nigella Sativa L. lipid complex seeds. All the experiments were carried out in accordance with the requirements of the State Pharmacopoeia, 14th Ed, given in the corresponding general pharmacopeial monographs.

Results. Profiles have been established and the content of fatty acids, sterines, triterpene alcohols, essential oils and thymoquinone found out in the lipid complex, has been estimated. The saponifiable portion of the complex is represented by triglycerides (81.7–95.3%), di- (3.9–15.2%) and monoglycerides (0.7–4.1%). They mainly contain linoleic (55.8–60.6%), oleic (21.8–24.6%), palmitic (10.0–12.8%), stearic (2.4–3.2 %) and cis-11.14-eicosadiene (2.3–2.6%) acids. In the lipid complex, the contents of sterines and triterpene alcohols were 0.4–0.7%; up to 70% of the fraction was represented by β-sitosterol (22.5–29.2%), cycloartenol (20.1–36.6%) and 24 methylenecycloartanol (9.5–19.9%). In the trace amounts (up to 1.0%), cholesterol has been detected in all the samples. In the lipid complexes, the content of thymoquinone ranged from 0.7 to 2.6%.

Conclusion. A comparative study of the seeds lipid complex of Nigella Sativa L. grown under various geographic conditions, has been carried out. The marker compounds as well as their content standards for determining the authenticity of raw materials (thymoquinone, para-cimen, cis-11.14-eicosadienic acid), have been identified.

Pharmacy & Pharmacology. 2020;8(1):29-39
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HPLC METHODS OF FEXOFENADINE QUANTITATIVE ANALYSIS IN RABBITS’ LIVER

Mylnikov P.Y., Chernykh I.V., Shchulkin A.V., Popova N.M., Yakusheva E.N.

Abstract

The investigation of pharmacokinetics of marker substrates of carrier protein P-glycoprotein (Pgp, ABCB1-protein) including fexofenadine, is one of the methods of its functional activity evaluation.

The aim of the study was to work out the HPLC methods of the quantitative determination of fexofenadine in rabbits’ liver.

Materials and methods. The quantitative determination of fexofenadine was performed using Stayer chromatographic system (Akvilon, Russia) with UVV 104 ultraviolet detector. Reverse-phased chromatographic column Luna C18 100Å (250*4.6) was used with 5 µm granulation at 45°С. The сoncentration of fexofenadine was determined by methods of absolute peak area calibration.

Results. The work was conducted in the isocratic mode. The composition of the mobile phase consisted of deionized water, acetonitrile and glacial acetic acid at the ratio of 267.4:120:4.33 brought to pH=6.7 with triethylamine.

The sample processing was in the form of homogenization of 500 mg of ground liver in 500 µl of purified water with the subsequent centrifugation (1750 g) and selection of the supernatant. The proteins were precipitated by acetonitrile (2.5 ml) acidified with 375 µl of hydrochloric acid by shaking at 500 rev/min.

The supernatant was transported into a separate test tube, where methylene chloride, diethyl ether and ethyl acetate were added (2 ml each). Then the solution was again shaken for 10 minutes (500 rev/min). After that, the solution was centrifuged (1750 g) and the supernatant was evaporated on a rotor-vacuum evaporator at 50°С. 300 µl of the mobile phase was added to the dry residue, and 100 µl was injected into the chromatograph.

The method was validated in the linear range from 3 to 60 µg/g of fexofenadine with the acceptable intra- and intercycle accuracy, precision and stability. The method was tested on rabbits after the intravenous administration of fexofenadine at the dose of 11 mg/kg.

Conclusion. The HPLC methods of fexofenadine quantitative determination in the hepatic tissue of rabbits has been worked out. It can be used for the evaluation of the functional activity of Pgp in preclinical studies.

Pharmacy & Pharmacology. 2020;8(1):40-47
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BETAMETHASONE ADMINISTRATION AS A TREATMENT OF CHOICE IN LOCAL POST-TATTOO COMPLICATIONS

Karymov O.N., Vorobyov A.A., Kalashnikova S.A., Polyakova L.V., Vyskub M.N.

Abstract

The aim of the study is to determine the effectiveness of betamethasone in the treatment of local post-tattoo complications, depending on the mode of administration.

Materials and methods. The work was carried out on 90 male rats which had been tattooed (n = 30 – a negative control group; n = 30 – a comparison group: a subcutaneous administration of 1 ml of a betamethasone solution; n = 30 – an experimental group: an administration of 1 ml of a betamethasone solution using a tattoo machine), 15 – intact rats. Withdrawal from the experiment took place on the 3rd, 10th and 21st days. The skin samples were fixed in 10% formalin, followed by histological posting and manufacturing of micropreparations, then staining with hematoxylin and eosin, according to Van Gieson. A morphometric study included determination of the volume fraction (VF) of the epidermis; dermal fibers; pigment; inflammatory cells; macrophages (%), as well as the pigment depth (μm) and the severity of edema.

Results. The study found out that in the process of the betamethasone administration using a tattoo machine, the drug was uniformly administrated over the entire area of the tattoo; hereby, the phenomena of edema and inflammatory infiltration were insignificant. The dermal fibers were located in each layer with no signs of edema and with single cells of inflammation, respectively. The data of the histological processing were completely consistent with the results of morphometry: it was found out that in the experimental group, edema significantly decreased, the volume fraction of the pigment and macrophages decreased, and the volume fraction of the dermal fibers increased. The estimation of the inflammatory reaction was carried out according to the morphometric parameters of the volume fraction of inflammatory cells and had significant differences in all the experimental groups, decreasing in the following series: the negative control group> the comparison group> the experimental group> the group of intact animals (p <0.05).

Conclusion. Based on the data obtained, the effectiveness of betamethasone in the treatment of local post-tattoo complications has been proved. In this case, the treatment of choice is the administration of this drug not traditionally subcutaneously, but using a tattoo machine that enables the targeted delivery of the substance to the area of the pathological process.

Pharmacy & Pharmacology. 2020;8(1):48-56
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RETROSPECTIVE ANALYSIS OF ADVERSE DRUG REACTION REPORTING FORMS ASSOCIATED WITH PENICILLIN FAMILY ANTIBIOTICS (PCNE-DRP 9.0) BASED ON DRUG-RELATED APPROACH

Matveev A.V., Krasheninnikov A.E., Egorova E.A., Koniaeva E.I.

Abstract

A widespread use of β-lactam antibiotics such as penicillins in practical medicine, and its authorized use in special categories of patients (e.g. children, pregnant and lactating women, the elderly) requires a critical investigation of their safety as well as the obligatory risk assessment before conducting antibacterial pharmacotherapy.

The aim of the work was the conduction of a retrospective study of adverse reactions cases, the identification and analysis of drug-related problems (DRP) associated with the use of penicillin family antibiotics.

Materials and methods. The objects of the study were adverse drug reactions (ADR) associated with the use of penicillin family antibiotics in inpatient and outpatient facilities, as well as the cases of self-treatment, which were recorded in the official ADR reports and then inputted in the regional (Republic of Crimea) database of spontaneous reports called ARCADe (Adverse Reactions in Crimea, Autonomic Database). The covered period is 2009–2018. The analysis of DRP was carried out using the 9.0 version of the qualification system DRP PCNE (Pharmaceutical Care Network Europe Foundation).

Results. The data analysis of ADR reporting forms has revealed that Amoxicillin clavulanate and Amoxicillin were the most frequent cause of ADR. A high incidence of penicillins ADR in pediatric patients (from 0 to 18 years) – 142 cases – has been found. The clinical manifestations of reactions included drug hypersensitivity reactions (309 cases), dyspeptic disorders (28 cases) and disorders of the central nervous system (5 cases). The incidence of serious ADR was 113 cases (33% of the total number of ADR in the study), which indicates a rather high risk of developing severe ADR for penicillins, resulted in a significant decrease in the quality of patients’ lives.

Conclusion. The detection of DRP using the PCNE V9.0 approach is a useful and promising tool important to improve the quality of pharmacotherapy and their adherence to treatment. The highest DRP values which were observed for Amoxicillin clavulanate and Amoxicillin, may indicate a high frequency of irrational use of these drugs.

Pharmacy & Pharmacology. 2020;8(1):57-64
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PROBLEMS OF PHARMACEUTICAL PROVISION OF POPULATION WITH HYPOLIPIDEMIC DRUGS: THE CASE OF THE VOLGOGRAD REGION (THE RUSSIAN FEDERATION)

Tyurenkov I.N., Knyazeva J.S., Ganicheva L.M., Kaysheva N.S.

Abstract

The aim of the study is to study the regional hypolipidemic drugs market, external and internal factors affecting their level of consumption, including the information awareness of the final customers about this pharmacotherapeutic group and the adherence to treatment with these drugs.

Materials and methods. The study was carried out using the methods of SWOT and STEP-analyses to assess the factors affecting the consumption of the studied group of drugs, as well as the questionnaire method of final customers and assessing their compliance using the Morisky-Green questionnaire.

Results. The influence of environmental and internal factors on the level and structure of the consumption of hypolipidemic drugs has been studied, hereby, the problems of the group and ways to solve them have been outlined, and an increase or decrease in the need for hypolipidemic drugs at the regional level, have been predicted. The assessment of the information awareness and preferences of the final customers of hypolipidemic drugs has been carried out, and insufficient awareness of patients about the drugs under study, has been revealed. The compliance of the final customers has been studied. A low level of the compliance of the patients to the prescribed hypolipidemic therapy has been established.

Conclusion. Modern advances in the treatment of cardiovascular diseases, based on fundamental achievements of science and practice, have created a high evidence base for the choice of strategies for pharmacotherapy with hypolipidemic drugs. The main ways to increase information awareness and compliance of the final customers are: development and intensification of educational programs to increase the level of knowledge and information awareness of doctors and pharmaceutical professionals, establishing the Doctor-Patient partnering relationships, increasing the trust level to the doctor and, as a result, the level of the patient compliance уровень; the development of materials for increasing the information awareness among the final customers about hypolipidemic drugs and hypolipidemic therapy in general.

Pharmacy & Pharmacology. 2020;8(1):65-73
pages 65-73 views

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