Drug Development and Registration最新文献

{"title":"Development of Genistein Synthesis for Use as a Certified Reference Material","authors":"А. Жигалина, Г. Дударев, В. Тихонова, О. Ю. Стрелова, A. A. Zhigalina, Vladimir G. Dudarev, Viktoria V. Tikhonova, O. Strelova","doi":"10.33380/2305-2066-2021-10-4(1)-20-31","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-20-31","url":null,"abstract":"Introduction. The use of certified reference materials (CRMs) ensures metrological traceability and comparability of analysis results performed in different laboratories, by different analysts, at different times. Genistein is a promising substance with a wide spectrum of pharmacological action. genistein is widely used in dietary supplements. Development of regulatory documents for CRM of genistein will ensure the quality of drugs and dietary supplements.Aim. Aim of our study is to improve of the ways of synthesis and determination of spectrum characteristics of genistein for the certification of CRM.Materials and methods. We used synthetic genistein, (Ph.D. V. Yu. Kovtun SPC \"Pharmzashchita\") (sample № 1) and genistein synthesized and studied at the departments of pharmaceutical chemistry and chemical technology of medicinal substances SPCPU (sample № 2). Infrared spectra of genistein samples were collected on an FSM 1201 infrared Fourier spectrometer (OOO Infraspek, Russia) via KBr pellets technique. All the spectra were collected in the 4000–500 cm−1 range. The NMR (1H and 13C) measurements were performed with a BrukerAvance III NMR spectrometer (400 and 100 MHz) (Bruker, Germany) in DMSO-d6 solvent. Raman spectra were recorded by an ORTES-785TRS-2700 analytical Raman scattering system at a laser power of 100 mW (OPTEC JSC, Russia). Laser interaction time was 5, 10, 20 and 60 seconds. The results were processed using the software \"BWSpec 4.10_4\", USA. GC-MS was performed on an Agilent Technologies 7890A gas chromatograph (Agilent Technologies, USA) with a 7693 autoinjector and a Hewlett Packard 5975C mass selective detector.Results and discussion. The synthesis was carried out according to the developer's method. The stage \"removal of the alkyl protection\" has been improved. The spectra of the synthesis intermediate of genistein (biochanin A) correspond to the literature data. Samples of genistein were investigated by methods: MC and NMR 13С, 1Н. The structure of the investigated substance was confirmed; Raman and IR spectroscopy showed that the spectra of the samples do not differ from each other and there are no additional signals.Conclusion. The spectrum characteristics of samples of genistein were obtained by NMR, IR and Raman spectroscopy, which will be used in the regulatory documentation for CRM of genistein. All of this will make it possible to control the quality of medicines based on it and to identify substandard dietary supplements.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46825406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation of formononetin-7-O-β-D-glucopyranoside from the grass of Ononis arvensis L. and the assessment of its effect on induced platelet activation","authors":"A. Bogoutdinova, A. Whaley, A. O. Ponkratova, A. Orlova, M. Goncharov, V. Shpakova, N. Farmanova, D. K. Nurullaeva, A. T. Sharipov, S. Gambaryan, M. Povydysh","doi":"10.33380/2305-2066-2021-10-4(1)-14-19","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-14-19","url":null,"abstract":"Introduction. Analysis of the clinical and laboratory picture of the SARS-CoV-2 infection suggests the presence of microcirculation and oxygen transport disorders, hemolysis of erythrocytes, intra-alveolar fibrin formation and microthrombus formation in the patient’s pathogenesis. Accordingly, the search for potential anticoagulants, erythrocyte antiplatelet agents, membrane stabilizing drugs and mild thrombolytic drugs can prevent the development of life-threatening complications and reduce the mortality of COVID-19 patients.Aim. Isolation of formononetin-7-O-β-D-glucopyranoside from the grass of Ononis arvensis L. and identification of the molecular mechanisms of its effect on platelet activation in vitro, induced by TRAP-6 (Thrombin receptor activated peptide) and ADP (adenosine diphosphate).Materials and methods. Terrestrial parts of Ononis arvensis L. were collected in the SPCPU nursery of medicinal plants (Leningrad region, Vsevolozhsky district, Priozerskoe highway, 38 km). Isolation of formononetin-7-O-β-D-glucopyranoside was carried out by preparative high performance liquid chromatography on a Smartline device (Knauer, Germany) equipped with a spectrophotometric detector. The structure of formononetin-7-O-β-D-glucopyranoside was confirmed by one-dimensional and two-dimensional NMR spectroscopy (Bruker Avance III, 400 MHz, Germany), as well as high-resolution mass spectrometry (HR-ESI-MS) (Bruker Micromass Q-TOF, Germany). The study of the effect of formononetin- 7-O-β-D-glucopyranoside on induced platelet activation was carried out on human platelets isolated from the blood of healthy volunteers. To research the effect of formononetin-7-О-β-D-glucopyranoside on platelet aggregation flow cytofluorometry with Cyto-FLEX (Beckman-Coulter, USA) was used.Results and discussion. According to the method of fractionation and purification of the total extract of O. arvensis developed in previous studies, formononetin-7-O-β-D-glucopyranoside was isolated in an individual form for subsequent biological studies with a total yield of 30 % in comparison with its content in the original extract. In samples with formononetin-7-O-β-D-glucopyranoside and ADP, there is a pronounced inhibition of platelet activation – the percentage of active platelets ranges from 6.3–6.6 % at doses of formononetin-7-O-β-D-glucopyranoside 1 μM, 3 μM and 30 μM. The inhibitory effect of formononetin-7-O-β-D-glucopyranoside is not dose-dependent (p ≤ 0.05). In samples with formononetin-7-O-β-D-glucopyranoside and TRAP, there is also a pronounced inhibition of platelet activation. The percentage of active platelets is 8 % at 1 μM formononetin-7-O-β-D-glucopyranoside doses, 15 % at 3 μM doses, and 16 % at 30 μM doses.Conclusion. Administration of formononetin-7-O-β-D-glucopyranoside at doses of 1 μM, 3 μM, 30 μM strongly inhibits platelet activation induced by ADP and TRAP-6. For ADP, there is no dose-dependent effect, while for TRAP there is a weak dose-dependent effect, the gr","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47777656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of the composition of prolonged release tablets based on 4,4'-(propandiamido) sodium dibenzoate using the SeDeM method","authors":"Михаил Игоревич Коцур, Ю. М. Ладутько, Артем Наркевич, Julia M. Kotsur, Julia M. Ladytko, I. Narkevich, E. Flisyuk","doi":"10.33380/2305-2066-2021-10-4(1)-54-62","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-54-62","url":null,"abstract":"Introduction. Direct compression technology is one of the most common tablet technologies. As known, many active pharmaceutical ingredients are not suitable for this technology without the addition of special excipients. A useful tool for determining the suitability of powdered materials for direct compression technology is the Sediment Delivery Model (SeDeM) method, based on the concept of Quality by Design. The presented method allows not only to assess the suitability of a material for direct compression, but also helps to predict the composition of a solid dosage form in the form of a tablet, which, in turn, leads to a significant reduction in experimental work carried out in the development of a new drug.Aim. Prediction of the compositions of matrix tablets based on sodium 4,4'-(propanediamido)dibenzoate with prolonged release, obtained by direct compression using the method of mathematical modeling SeDeM.Materials and methods. The objects of the study were the original substance sodium 4,4'-(propanediamido)dibenzoate, as well as a number of auxiliary substances, which included polymers used for dosage forms with prolonged release, a dusting component – magnesium stearate, and a filler – lactose monohydrate. Physicochemical and technological properties of APIs, explosives, obtained tablet mixtures and tablets were studied in accordance with the requirements of the State Pharmacopoeia of the Russian Federation XIV ed. and EP 9th ed.Results and discussion. The properties of the substance and excipients were assessed in accordance with the SeDeM method. It was found that the substance 4,4'-(propanediamido) sodium dibenzoate is not suitable for direct pressing due to poor flowability and low compressibility. Hypromellose Methocel K4M had good compressibility, but it did not have sufficient flowability. The other tested polymers had satisfactory properties for the direct compression technology. The composition of the tablet mixtures was calculated using the SeDeM method, the obtained tablet mixtures had satisfactory technological characteristics for obtaining tablets by direct compression. The tablets obtained as a result of the experiment also met the pharmacopoeial requirements.Conclusion. Prediction of the composition of sustained-release tablets based on the original substance sodium 4,4'-(propanediamido)dibenzoate was carried out using the SeDeM method. It was found that this method is suitable for the development of the composition of tablets based on sodium 4,4'-(propanediamido)dibenzoate.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42158057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a mafedine lyophilizate for parenteral use","authors":"А. Терентьева, А. Вайнштейн, В. В. Тихонова, А. К. Уэйли, М. А. Трофимов, Вероника Александровна Приходько, Л. В. Шигарова, O. A. Terenteva, V. Vainshtein, V. V. Tikhonova, A. Whaley, M. A. Trofimov, V. Prikhodko, L. V. Shigarova","doi":"10.33380/2305-2066-2021-10-4(1)-88-94","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-88-94","url":null,"abstract":"Introduction. Cerebrovascular disease (CVD) is the most important medical and social problem of modern neurology because they have the highest rates of morbidity, mortality and disablement in the population. The growing incidence of CVD as a result of an aging population worldwide requires the emergent development of therapeutics, diagnostic and preventive tools. However, the development of drugs for the treatment of brain diseases has limitations due to the presence of the blood-brain barrier, which protects the brain against most molecules from the bloodstream entering the central nervous system. At the St. Petersburg State Chemical Pharmaceutical University of the Ministry of Health of Russia the alpha-2 adrenergic agonist mafedine was synthesized, which has mild psychostimulant and anxiogenic effects and which may be used in the treatment of traumatic brain injury as a neuroprotective agent.Aim. The development of a dosage form of mafedine in order to improve its penetration into the central nervous system.Materials and methods. Mafedine (pharmaceutical substance) [6-oxo-1-phenyl-2-(phenylamino)-1,6-dihydropyrimidin-4-olate sodium] (St. Petersburg State Chemical-Pharmaceutical University of the Ministry of Health of Russia); lecithin, span-60, Tween-80, Poloxamer 188, mannitol, vitamin E, ascorbic acid, methylene chloride, dimethyl sulfoxide, acetonitrile, trifluoroacetic acid. The fine emulsion of mafedine was obtained by ultrasound. The dosage form of mafedine was obtained by freeze drying. Residual solvents were determined by gas chromatography. Quantitative analysis of mafedine was performed by high-performance liquid chromatography. Particle size and zeta potential of emulsion were determined on a Zetasizer Nano ZS.Results and discussion. Lyophilizate of mafedine was obtained and presenting as a light yellow porous, odorless tablet. The average mass of dry tablet was (0,17 ± 0,01) g with mafedine content is (26 ± 1) mg. The water content in the lyophilizate was 3,85 %. The quantity of methylene chloride in the lyophilizate correspond to the requirements for residual solvent content. The reconstitution time of lyophilizate into a primary emulsion was 3–5 seconds. The reconstituted dispersion was yellow, odorless, and did not break within 2 days during storage. The pH of the reconstituted emulsion was 7,34. The average particle size was (164,7 ± 6,4) nm, the zeta potential was –32 mV.Conclusion. The developed dosage form is stable according to its physicochemical and pharmaceutical characteristics and is suitable for experimental study on models as a neuroprotective and neurorehabilitation agent.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42341710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The sodium 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidine-4-olate quantitative content determination in a standard sample","authors":"E. Kuvaeva, D. A. Kolesnik, P. O. Levshukova, I. I. Terninko, I. Yakovlev, E. V. Fedorova","doi":"10.33380/2305-2066-2021-10-4(1)-115-121","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-115-121","url":null,"abstract":"Introduction. The standard samples (SS) use is a necessary condition for the medicines' quality control implementation. Their development is an urgent problem for the pharmaceutical industry, especially for new biologically active compounds that can be further used as pharmaceuticals.Aim. This work aim is to establish the 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydro pyrimidone-4-olate sodium quantitative content, for which anti-inflammatory and analgesic activity was previously proven, in a standard sample.Materials and methods. This work aim is to establish the 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydro pyrimidone-4-olate sodium quantitative content, for which anti-inflammatory and analgesic activity was previously proven, in a standard sample. The main method for establishing a substance quantitative content in the SS is the material balance method. The water determination was carried out according to K. Fisher's method (semimicro method). Sulphated ash was determined according to the XIV edition Russian Federation State Pharmacopoeia General Pharmacopoeia Monograph \"Sulphated ash\". Related impurities and their content were assessed using the HPLC method on a Flexar liquid chromatograph equipped with a diode array detector (Perkin Elmer, USA). The residual solvents' determination was carried out by the headspace method using a gas chromatograph GC-2010Plus Shimadzu with a flame ionization detector. As an additional method for establishing the main component quantitative content, acidimetric titration with the equivalence point potentiometric indication was carried out.Results and discussion. The percentage was determined for the following indicators: water, residual organic solvents, related impurities, sulphated ash. Using the material balance method, it was found that the 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidin-4-olate sodium percentage in a standard sample is 96.01 ± 0.50 %. It was found by acidimetric titration that the 5-butyl-1,2-diphenyl-6-oxo 1,6-dihydropyrimidin- 4-olate sodium quantitative content in SS is 95.12 ± 0.02 %. The difference in the certified value can be explained by the fact that during titration, the SS aciform is released, which precipitates in an aqueous medium and contributes to a shift in the equilibrium and pH value. Consequently, the equivalence point is reached somewhat earlier. However, the data are practically comparable, but it is necessary to use the value obtained by the material balance method.Conclusion. A standard sample certification parameters were determined: water content, residual organic solvents, sulphated ash, related impurities. The main component quantitative content was determined using the material balance method and titrimetry (acidimetry with the equivalence point potentiometric indication).","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43120105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Anatomical Characteristics of the Leaf Blades of the Several Species of Crataegus L.","authors":"V. A. Sagaradze, E. Babaeva, E. Kalenikova, N. A. Trusov, E. V. Peshchanskaya","doi":"10.33380/2305-2066-2021-10-4-138-146","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-138-146","url":null,"abstract":"Introduction. The Crataegus L. (Hawthorn) is a common herb in numerous Pharmacopoeias. The State Pharmacopoeia of the Russian Federation provides hawthorn fruits and flowers for medical utilization. With that, the literature data confirms the medical utility of hawthorn leaves since the “leaves” and the “flowers with leaves” have pharmacopoeial status worldwide. Therefore, those are considered as prospective forms of Crataegus raw material for Russian pharmaceutical production. However, most species remain poorly pharmacognostically investigated regarding the quantitative microscopic characteristics (the sizes of stomatal apparatus (SA) and epidermal leaf blade (LB) trichomes), which could be substantial for establishing the authenticity of the raw material.Aim. Examine epidermal anatomy of Crataegus spp. Leaf blades (LBs) and perform a comparative study of several quantitative diagnostic features of LBs of hawthorn plants from the sect. Sanguineae and the sect. Crataegus, growing in diverse regions of the Russian Federation.Materials and methods. Samples of hawthorn leaves (C. sanguinea, C. maximowiczii, C. dahurica, C. rhipidophylla, C. monogyna and C. pallasii) were collected in natural habitats in Western Siberia (Kemerovo) and in arboretums of Botanical Gardens (Moscow, Stavropol). Measurements of anatomical structures were carried out using a light microscope accompanied by an ocular micrometre.Results and discussion. The LB surface phenotypic diversity within hawthorn species and sections was studied. The LBs were described in terms of meterages (longitude and width) of SA, meterages and shape of sedentary multicellular leaf teeth glands. The peculiarities of pubescence and the sizes of simple unicellular non-glandular trichomes were also observed.Conclusion. The results of quantitative anatomical examination provided the characteristic features determining these elements at the species and section levels. Thus, it may facilitate authentication and quality control of whole or ground Crataegus medicinal raw material.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44891598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the Physical and Chemical Characteristics of the Zeolites of the Kholinsky Deposit","authors":"В. Бондарев, Т. Жилякова, Н. Б. Демина, К. К. Размахнин, Alexander V. Bondarev, Elena T. Zhilyakova, Natalya B. Demina, Konstantin K. Razmakhnin","doi":"10.33380/2305-2066-2021-10-4-65-71","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-65-71","url":null,"abstract":"Introduction. The mineral resource base of Russia has effective sorption substances that meet pharmaceutical requirements. Promising mineral raw materials are Zeolites, which combine the properties of an adsorbent and a \"molecular sieve\" due to the porous structure. In addition to the enterosorption direction, natural Zeolites are a source of macro-and microelements, which determines their use as biologically active food additives.Aim. Study of the physical and chemical characteristics of the Zeolites of the Kholinsky deposit.Materials and methods. The zeolite mineral raw materials of the Kholinsky deposit were used as objects of research. Optical microscopy was performed using a Leica DM direct microscope (Microsystems, Germany). Energy dispersion analysis was performed using an electron scanning microscope JSM-5300 (Jeol Ltd, Japan). The sorption characteristics were studied using the ASAP 2400 device (Micromeritics, USA) according to the method. The construction of a virtual three-dimensional molecular model of the Zeolite was carried out using the program Java Applet Jmol.Results and discussion. The physicochemical properties of Zeolites are investigated. It is established that morphologically the particles of the zeolite phase have a size of 5-30 microns, they are evenly distributed over the entire area of the site and represent the first structural level. Particles of the zeolite phase with a size of 5-6 microns form the second structural level due to Clinoptilolite crystals, microcracks and microgeodes. Based on the energy-dispersion spectral analysis, an increased content of the elements K, Na was revealed, which indicates the alkaline composition of the cation exchange complex. The studied Zeolite samples have micropores (volume 0.0031 cm3/g), mesopores (volume 0.0675 cm3/g), and a specific surface area of 29.1840 m2/g. A virtual three-dimensional molecular model of the Zeolite of the Kholinsky deposit has been developed. According to the molecular model, the sorption characteristics of the Kholinsky deposit Zeolite were: specific surface area - 1096.31 m2/g (1916.34 m2/cm3), the average diameter of the spherical molecule for adsorption in the pores is 5.97 A.Conclusion. The analysis of the sorption characteristics of the Zeolite revealed the following features: the pores occupy half the volume of the entire Zeolite, which are available for the sorption of water and low-molecular substances. Each pore in three mutually perpendicular directions communicates with the neighboring ones through \"windows\". A system of intracrystalline pores and cavities is formed, in which the occlusion and adsorption of molecules of the appropriate size easily occurs.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42811398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating the Antifungal Activity of Antimycotic Drugs with Farnesol","authors":"N. Sachivkina, A. Senyagin, I. Podoprigora, D. Brown, V. V. Vissarionova","doi":"10.33380/2305-2066-2021-10-4-162-168","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-162-168","url":null,"abstract":"Introduction. Clinical strains of microorganisms, including opportunistic yeast-like fungi (YLF) of the genus Candida, are resistant to currently used antifungal drugs. In this regard, the search for alternative ways to potentiate the activity of antimicrobial agents in relation to the infectious agent is an important and relevant area of research. The study of combinations of existing antimycotic drugs and a medicinal extract of plant origin – farnesol – is one of the promising approaches in the fight against resistant strains of YLF genus Candida. In our previous studies, farnesol has been shown to exhibit relative activity against YLF Candida albicans biofilms. In this study, we used 6 clinical isolates and one museum strain YLF C. albicans to study the effect of farnesol on the antifungal activity of antimycotic drugs.Aim. To prove that farnesol can increase the antifungal activity of certain antimycotics.Materials and methods. To determine the sensitivity of 7 strains of YLF C. albicans to the antimycotic drugs \"Nystatin\" (NYS 50 µg), \"Ketoconazole\" (KET 10 µg), \"Clotrimazole\" (CTR 10 µg), \"Amphotericin B\" (AMB 10 µg), \"Voriconazole\" (VRC 10 µg) disk diffusion test was used. A solution of farnesol in concentrations of 100, 50 and 25 µM in a volume of 25 µl was applied to the disk with the antimycotic drug. Sterile physiological (PhS) solution was used as a control (pH 7.0; V = 25 µl).Results and discussion. In 34.3 % of of experiments we can talk about the modulating effect of farnesol solutions on the antifungal activity of antimycotic drugs. In all these cases, the sensitivity of YLF C. albicans to the antimycotic drug increases.Conclusion. The results of this study provide useful information for understanding the mechanism of QS-molecules action with antifungal activity, as well as they are the basis for the practical application of some QS-molecules in the treatment of infectious diseases caused by YLF of the genus Candida. The study demonstrates that farnesol can be recommended as an active substance that improves the sensitivity of YLF Candida to antimycotic drugs, especially in the case of multi-resistant strains Candida.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46476016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant Activity of Silver-containing Bionanocompositions Based on Humic Substances in Cell Culture","authors":"E. Buyko, M. V. Zykova, V. V. Ivanov, K. A. Bratishko, A. A. Ufandeev, I. O. Grigorieva, A. V. Tsupko, D. A. Mikhalyov, I. Perminova, M. Belousov","doi":"10.33380/2305-2066-2021-10-4-46-53","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-46-53","url":null,"abstract":"Introduction. Silver nanoparticles are promising agents for suppressing resistant strains of microorganisms and accelerating the purulent wounds healing. Oxidative stress disrupts normal wound healing processes, which leads to the formation of chronic non-healing wounds. Therefore, the determination of the ability of new wound healing agents to decrease the production of reactive oxygen species is a relevant task.Aim. The aim of the current study was to investigate the effect of silver-containing bionanocompositions based on humic substances on the basal and tert-butyl hydroperoxide-stimulated production of reactive oxygen species at the normal fibroblasts 3T3-L1 cell culture in vitro.Materials and methods. The study was carried out on 7 samples of initial humic substances and biomaterials with silver nanoparticles synthesized in the Laboratory of Natural Humic Systems, Faculty of Chemistry, Moscow State University named after M. V. Lomonosov. The intracellular production of reactive oxygen species was assessed using a 2,7-dichlorodihydrofluorescein diacetate fluorescent probe. Cells were cultured with samples for 24 h; tret-butyl hydroperoxide was used to stimulate the production of reactive oxygen species. Detection was performed fluorometrically using a microplate reader.Results and discussion. The most pronounced antioxidant activity was demonstrated by three samples of biomaterials with silver nanoparticles ultradispersed in humic substances matrices (CHS-AgNPs, CHP-AgNPs and CHE-AgNPs), which allows us to consider them as the most promising pharmaceutical agents for the treatment of purulent-inflammatory processes. The most probable mechanism of the high antioxidant activity of the studied biomaterials in relation to intracellular reactive oxygen species is the intrinsic activity of humic substances to bind reactive oxygen species, while silver nanoparticles in biomaterials catalyze the reduction processes of their interaction with reactive oxygen species.Conclusion. For the studied samples of biomaterials with silver nanoparticles ultradispersed in matrices of humic substances pronounced antioxidant activity was shown. Together with antibacterial properties, it makes it possible to consider them as potential agents for purulent wounds healing accelerating.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47001675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of the physicochemical properties of the etravirine substance","authors":"S. Zolotov, E. Ponomarev, I. A. Dain, N. Demina, A. Zolotova","doi":"10.33380/2305-2066-2021-10-4-28-35","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-28-35","url":null,"abstract":"Introduction. Etravirine, being one of the most popular antiretroviral drugs, doesn't have its physicochemical properties sufficiently described in scientific publications. Detailed information on the substance properties is necessary both for organizing the synthesis and for justifying the dosage form and technology for its production, as well as for identifying bottlenecks and critical parameters that affect the quality of the finished product.Aim. Study the etravirine physicochemical properties to model the design of studies to create an innovative dosage formMaterials and methods. Etravirine (MSN Life Sciences Pvt. Ltd., Hetero Labs Ltd.). The melting point was determined by the capillary method. Etravirine samples were studied via differential scanning calorimetry (DSC), X-ray powder diffractometry, IR and NMR spectroscopy. Particle size was determined using laser diffraction analysis. The shape and size of the crystals were determined with the help of transmission electron microscopy (TEM). The concentration of etravirine in aqueous media was determined using the HPLC method with a fluorescence detector. The concentration of etravirine in organic solvents was determined spectrophotometrically.Results and discussion. The X-ray powder diffractometry and IR spectroscopy helped to determine the fact that the studied substances represent the same polymorphic modification. The melting point of etravirine ranges from 259 to 263 °C. Melting is accompanied by decomposition. The substance is practically insoluble in aqueous media at pH values in the range from 1.2 to 6.8, soluble in some organic solvents, readily soluble in dimethyl sulfoxide, tetrahydrofuran, dimethylformamide, dimethylacetamide. The distribution coefficient in the \"1-octanol/phosphate buffer solution pH 6.8\" solvent system was 5.22. The experiment showed that the etravirine substance is lipophilic. Etravirine is found to be a highly crystalline substance and represents needle-shape prismatic crystals.Conclusion. Etravirine is a lipophilic substance, practically insoluble in aqueous solutions, soluble in a number of organic solvents. The studied substances turned out to be the same polymorphic modification. Since the melting of the substance is accompanied by decomposition, high temperatures processes should be avoided.Conflict of interest. The authors declare that they have no obvious and potential conflicts of interest related to the publication of this article.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42232104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}