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Vol 24, No 12 (2021)


The principle of the integrated use of plant raw materials as a tool for resource-saving technologies for obtaining therapeutic and prophylactic agents

Saybel O.L.


The modern level of development of the pharmaceutical industry makes it possible to obtain from plants total, purified extracts, as well as individual biologically active substances (BAS) and their amounts. The creation of such products is achieved by a detailed study of the chemical composition of new plant species, the identification of active components, an assessment of their effectiveness and safety, and the solution of standardization issues. Technologies for the integrated use of raw materials are the most rational way of processing medicinal plants. Practical methods for implementing this principle are the use of the whole plant, the production of several substances in one production process, the secondary use of meal after extraction and cake after pressing. All the examples of the implementation of the principle of the integrated use of plant raw materials given in the article testify to its rationality and make it possible to ensure high-tech and economic feasibility of phytochemical industries. In this regard, it is this approach, if possible, should be applied in the study of new types of medicinal plants. To develop resource-saving technologies for the integrated use of new types of medicinal plants, a comprehensive science-based approach should be applied, combining theoretical and experimental research segments. Common chicory is a new plant species that is promising for complex use. The processing of its aboveground and underground parts can result in hepatoprotective and immunomodulatory pharmaceutical substances, as well as functional products in the form of inulin and feed additives for ruminants.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(12):3-10
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Criteria for evaluating the qualitative and quantitative characteristics of microcapsules

Semkina O.A., Beloshapkina O.M., Dzhavakhyan M.A.


The review presents material on the peculiarities of methods for assessing the quality of microcapsules of drug substances and the potential application of formal techniques and additional tests proposed for active pharmaceutical substances enclosed in microcapsules. We analyzed domestic and foreign sources of open access literature; the following digital databases were used: PubMed, Elibrary, CyberLenincka and the Google Scholar search engine. The effective tests proposed for microencapsulated substances and the need for additional tests for microcapsules depending on their composition and purpose were identified. Opportunities of microcapsules standardization as a dosage form for effective evaluation and understanding of qualitative and quantitative characteristics while considering microparticles as a pharmaceutical substance and a dosage form intended for use were described.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(12):11-17
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Comparative QSAR-modeling of cannabinoids-analgesics and non-steroidal anti-inflammatory drugs

Syroeshkin A.V., Galkina D.A., Pleteneva T.V., Morozova M.A., Levitskaya O.V.


Relevance. With prolonged use, non-steroidal anti-inflammatory drugs (NSAIDs) cause unwanted side effects. A possible alternative to NSAIDs can be medicines based on non-psychoactive plant cannabinoids, which have successfully proven themselves in the world market. But in the conditions of strict control over the circulation of narcotic drugs in Russian Federation, studies with cannabinoid substances are not possible. Purpose of the study. To characterize the biopharmaceutical parameters of two groups of analgesics using the quantitative structure-activity correlation (QSAR) method to demonstrate the advantages of cannabinoids over NSAIDs. Materials and methods. The objects of the study were two groups of analgesics, representatives of the class of NSAIDs and cannabinoids. QSAR method was used. Results. It was shown that the calculated Wiener (W) and Balaban (J) topological indices are in one-to-one correspondence with such biopharmaceutical parameters as equilibrium binding constants with CB1 and CB2 cannabinoid receptors, toxicity (LD50, mice/rat, per os), lipophilicity (logP). The LD50-W/J and logP-W/J diagrams clearly demonstrate that cannabinoids have higher lipophilicity and lower toxicity compared to NSAIDs. Conclusions. The results obtained open prospects for replacing NSAIDs with analgesic cannabinoid preparations and make it possible to recommend the approaches for assessing the toxicity and lipophilicity of new plant cannabinoids and their synthetic analogues.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(12):18-23
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Development of approaches to standardization of Juglans nigra L. leaves by HPLC

Kurkin V.A., Zimenkina N.I., Pomogaybin A.V.


Introduction. Juglans nigra L., family Juglandaceae), is a deciduous tree, which is one of the most promising types of medicinal plant raw materials. Due to the high content of biologically active compounds, Juglans nigra L. leaves are of interest as a new type of medicinal plant raw materials. In addition to the leading group of biologically active compounds (naphthoquinones), that the raw materials contain other chemical compounds, including flavonoids (quercitrin, myricitrin), which can make a significant contribution to the anti-microbial and tonic activity of the specified pharmaceuticals. The urgency of the problem is due to the fact that, despite the content of a large number of biologically active compounds and high pharmacological activity, the Juglans nigra L. leaves are not included in the State Pharmacopoeia of the Russian Federation. Consequently, there is a need for standardization of Juglans nigra L. leaves, including the development of quantitative determination meth- ods using modern methods of analysis. The article presents the results of studies on the development of quantitative analysis of myricitrin and quercitrinin, Juglans nigra L. leaves in order to include medicinal plant raw materials of Juglans nigra L. leaves in the State Pharmacopoeia of the Russian Federation. The study was carried out within the framework of the complex Research and development work topics of SamSMU "Chemical-pharmaceutical, biotechnological, pharmacological and organizational-economic research on the development, analysis and use of pharmaceutical substances and drugs" (No. АААА-А19-119051490148-7 dated 05.14.2019). The purpose of the study. Development of methods for a quantitative analysis of biologically active compounds of Juglans nigra L. leaves, namely myricitrin and quercitrin. Material and methods. The objects of the study were samples of Juglans nigra L. leaves harvested in March-April 2018-2020 on the territory of the Botanical Garden of Samara University (Samara), received by the team of the Department of Pharmacognosy with Botany and Fundamentals of Phytotherapy of SamSMU reference standard of myricitrin and quercitrin with a purity of at least 98%. High-performance liquid chromatography (HPLC) was used as methods for analyzing the extracts, which was carried out using a Milichrom-6 chromatograph (NPAO "Nauchpribor") under the following conditions of reverse phase chromatography in an isocratic mode: steel column "KAKH-6-80-4" (No2; 2 mm x 80 mm; Separon-C18 7 microns), mobile phase-acetonitrile: 1% solution of acetic acid in water in a ratio of 2:8, 100 μL/min, eluent volume - 1500 μL. The substances were detected at a wavelength of 360 nm. The volume of injected samples for extraction from the bark of black walnut, as well as solutions of quercitrin and myricitrin 4 μl. The myricitrin and quercitrin content were calculated using the external standard method. The suitability of the chromatographic system was evaluated in accordance with the OFS. "Chromatography". Results. Using the method of column chromatography, the dominant flavonoids - myricitrin (myricetin - 3-O-α-L-rhamnopyranoside) and quercitrin (quercetin-3-O-α-L-rhamnopyranoside), were identified on the basis of UV, NMR, mass spectra, as well as the results of acid hydrolysis, were isolated from the water-ethanolic extractionof Juglans nigra L. leaves. Methods for the quantitative determination of myricitrin and quercitrin in Juglans nigra L. leaves by microcolumn HPLC under isocratic conditions (mobile phase - acetonitrile : 1% solution of acetic acid in water in a ratio of 2:8) have been developed. The error of a single determination of the content of myricitrin in the leaves of Juglans nigra L. with a confidence probability of 95% was ±4.91 %. The content of myricitrin varied (2.58±0.15)% to (2.67±0.13)%. In addition, the quercitrincontent varied from (1.36±0.12)% to (1.45±0.15)%. The error of a single determination of the quercitrin content in Juglans nigra L. leaves with a confidence probability of 95% was ±5.18 %. Conclusion. Results of the conducted studies have shown satisfactory metrological characteristics of the HPLC method for determining the quantitative content of myricitrin and quercitrin proposed for standardization of raw materials of Juglans nigra L.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(12):24-35
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Prediction of mechanisms of pharmacological action of a multicomponent herbal extract using the PASS online web resource on the example of the herb of chicoria

Adamov G.V., Saybel O.L., Mizina P.G.


Prediction of the biological activity of chemical compounds before conducting biological analyzes is now a common practice. Preliminary screening using software and mathematical methods allows you to identify the most promising chemical compounds and thereby significantly save expended resources, including reducing the number of required laboratory animals. For the first time, the article proposes to use the prediction of pharmacological activity for total herbal preparations. For this, using the open platform PASS online, the pharmacological activity of phenolic acids of chicory was predicted, and the effects were identified that coincide for most of the selected compounds. This approach makes it possible to level the probabilistic nature of the assessment for each individual compound and to suggest synergistic interactions. According to the data obtained, hypolipidemic, immunostimulating and antibacterial effects are predicted for chicory.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(12):36-40
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Determination of total triterpene saponins in a combined drug based on jacob’s ladder, motherwort herbs and hawthorn fruit by spectrophotometry

Hajjar F., Potanina O.G.


Purpose: The purpose was to evaluate analytical procedures for the quantitative determination of the total triterpene saponins in a combined herbal medicine based on motherwort herb, hawthorn fruit and jacob's ladder herb by ultraviolet-visible spectrophotometry. The article presents determining the amount of triterpene saponins in a combined sedative drug based on spissum extracts of pharma-copoeial medicinal plant raw materials of motherwort herb, hawthorn fruits and jacob's ladder herb, using spectrophotometry. In according to requirements of state pharmacopoeia th14, General Pharmacopoeia Monograph. "Spectrophotometry in the UV and visible regions" using a spectrophotometric method for determining the content of the sum of triterpene saponins in terms of β-escin. The conditions for the analysis were taken from the monograph of state pharmacopoeia th14. The method was validated according to requirements of General Pharmacopoeia Monograph 1.1.0012.15 "Validation of analytical methods" in terms of the parameters: specificity, linearity, correctness, repeatability and precision of solutions. The data obtained can be used in the development of regulatory documents for the developed combined drug in the form of a spissum extract.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(12):41-45
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Investigation of essential oils composition of Bupleurum bicaule Helm from Buryatia flora

Tykheev Z.A., Emelianova E.A., Abaturov A.N.


Relevance. The genus Bupleurum L. plants are one of the sources of biologically active substances. Determination of the qualitative composition and quantitative content of the essential oils components is necessary for the standardization of a new type of medicinal plant material. Purpose of research. Investigation of essential oils composition of Bupleurum bicaule from Buryatia flora. Material and methods. Plant materials were collected in the Khorinsk district of the Republic of Buryatia during the flowering period (July 2019). Essential oils from the herbs and roots were isolated by hydrodistillation method. The content of essential oils was found by the volumetric method. The qualitative composition and quantitative content of essential oils components were determined by gas chromatography-mass spectrometry method. Results. The qualitative composition and quantitative content of essential oils components of herbs and roots of the B. bicaule from Buryatia flora have been studied for the first time. The main components of essential oils from aerial part are β-myrcene (6.74%), trans-β-ocymene (18.75%), limonene (6.67%), β-pinene (5.28%), germacrene D (18.34%), caryophyllene (9.05%), bicycloger-macrene (7.61%) and undecane (5.35%). For essential oils of the roots, the main components are bicyclogermacrene (7.95%) and 6- tridecene-4-yne (71.64%). Conclusions. It has been shown that the aerial part of the B. bicaule is a rich source of terpene compounds, while the roots are source of polyyne compounds
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(12):46-51
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Evaluation of essential metal levels in subcutaneous and visceral adipose tissue samples from patients with morbid obesity: a pilot study

Skalny A.V., Chang J.-., Nikolenko V.N., Huang S.-., Zotkin D.A., Wang W., Tinkov A.A.


The objective of the study was to evaluate essential metal levels in subcutaneous and visceral adipose tissue samples from patients with morbid obesity. Adipose tissue samples were collected from 10 women with morbid obesity (BMI > 35) aged 30-50 y.o. Assessment of iron (Fe), copper (Cu), manganese (Mn), zinc (Zn), and selenium (Se) levels in adipose tissue samples was performed using inductively coupled plasma mass spectrometry. The obtained data demonstrate that iron and copper levels in visceral adipose tissue were 68% (p = 0,021) and 38% (p = 0,053) higher as compared to subcutaneous depot. No difference in tissue Mn, Se, and Zn levels were observed. The obtained values generally correspond to those reported in studies from Spain, Italy, and Lithuania. Correlation analysis demonstrated positive association between subcutaneous adipose tissue Fe, visceral adipose tissue Fe and Cu contents, and BMI values. Therefore, the obtained findings demonstrate heterogeneity of adipose tissue metal levels in patients with morbid obesity with predominant accumulation of Fe and Cu in visceral adipose tissue.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(12):52-56
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Analysis of morphological, physiological and biochemical features of saprophytic culture of Claviceps purpurea (Fries) Tulasne BKMF-2641D strain

Bobyleva P.I., Savin P.S.


Relevance. The strain of the fungus Claviceps purpurea (Fries) Tulasne BKMF-2641D is used in parasitic culture (on rye crops) to obtain medicinal raw materials containing the peptide ergoalkaloid ergotamine. The relevance of the study consists in solving the problem of saprophytic cultivation of the C. purpurea BKMF-2641D fungus strain for the production of ergotamine, which will allow the pharmaceutical industry to meet its growing needs for standard medicinal raw materials every year, regardless of the season, reduce production costs, create environmentally friendly production, and so on. Obtaining a mycelial culture of an ergot fungus is a starting point in solving both scientific and practical problems associated with the use of fungi - parasites C. purpurea (Fries) Tulasne as producers of biologically active compounds in a saprophytic culture and subsequently allows a comprehensive study of the cultivation of such a culturewithin artificial nutrient media. Material and methods. This paper presents the results of experiments aimed at obtaining a mycelial culture of ergot from the sclerotia of the strain of the parasite fungus C. purpurea BKMF-2641D with the subsequent study of growth, some morphological, physiological and biochemical characteristics of its cultivation in artificial nutrient media (T2, Tg and T25). Results. It was experimentally established that five to six days after placing a piece of sclerotium on the surface of agar medium T2, the growth of mycelium was visually recorded around it. The subsequent growth of the mycelium was accompanied by its compaction and filling both the entire surface of the slant T2 agar medium and inside the nutrient substrate. As the mycelium grew on days 20-30, its color changed from white to purple due to the fact that the pigment diffused into the nutrient medium. The fungus began to actively form conidia on the 14-30th day of growth. The density of the suspension of conidia in 10 ml of washout from the mycelium surface was 5.8±0.20x109 pcs/ml on the 30th day of growth. The culture of the fungus in liquid nutrient medium T25 was a suspension of mycelium and a small amount of conidia. The color of the culture liquid varied depending on the age of the culture: from milky white at the beginning to gray or sometimes beige at the end of fermentation. In this case, the synthesis of ergot alkaloids was not observed. Conclusion. The experiments showed that the transfer of the parasitic fungus strain C. purpurea BKMF-2641D to saprophytic cultivation conditions (both superficial and deep) ensures good growth of the fungus. However, under the conditions of the study, the genes responsible for the synthesis of ergotamine did not work. At the same time, these genes are not lost, but specific conditions are required for their work.
Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(12):57-62
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Pamyati Tat'yany Aleksandrovny Sokol'skoy

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Problems of Biological Medical and Pharmaceutical Chemistry. 2021;24(12):63-64
pages 63-64 views

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