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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">pharmjournal</journal-id><journal-title-group><journal-title xml:lang="ru">Разработка и регистрация лекарственных средств</journal-title><trans-title-group xml:lang="en"><trans-title>Drug development &amp; registration</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2305-2066</issn><issn pub-type="epub">2658-5049</issn><publisher><publisher-name>LLC «CPHA»</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.33380/2305-2066-2023-12-4-1585</article-id><article-id custom-type="elpub" pub-id-type="custom">pharmjournal-1605</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ФАРМАЦЕВТИЧЕСКАЯ ТЕХНОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>PHARMACEUTICAL TECHNOLOGY</subject></subj-group></article-categories><title-group><article-title>Совершенствование технологий выделения и очистки биологически активных веществ из растительного сырья</article-title><trans-title-group xml:lang="en"><trans-title>Improvement of Technologies for Isolation and Purification of Biologically Active Substances from Plant Raw Materials</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5121-2343</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Турманидзе</surname><given-names>Г. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Turmanidze</surname><given-names>G. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>197376, г. Санкт-Петербург, ул. Профессора Попова, 14, лит. А</p></bio><bio xml:lang="en"><p>14A, Prof. Popova str., Saint-Petersburg, 197022</p></bio><email xlink:type="simple">georgij.turmanidze@spcpu.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7262-0941</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сорокин</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Sorokin</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>197376, г. Санкт-Петербург, ул. Профессора Попова, 14, лит. А</p></bio><bio xml:lang="en"><p>14A, Prof. Popova str., Saint-Petersburg, 197022</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0000-5479-5257</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Степанов</surname><given-names>К. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Stepanov</surname><given-names>K. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>197376, г. Санкт-Петербург, ул. Профессора Попова, 14, лит. А</p></bio><bio xml:lang="en"><p>14A, Prof. Popova str., Saint-Petersburg, 197022</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0006-9032-1335</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Игнатенко</surname><given-names>М. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Ignatenko</surname><given-names>M. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>197376, г. Санкт-Петербург, ул. Профессора Попова, 14, лит. А</p></bio><bio xml:lang="en"><p>14A, Prof. Popova str., Saint-Petersburg, 197022</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный химико-фармацевтический университет» Министерства здравоохранения Российской Федерации (ФГБОУ ВО СПХФУ Минздрава России)</institution></aff><aff xml:lang="en"><institution>Saint-Petersburg State Chemical and Pharmaceutical University</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>12</day><month>10</month><year>2023</year></pub-date><volume>12</volume><issue>4</issue><fpage>71</fpage><lpage>79</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Турманидзе Г.Н., Сорокин В.В., Степанов К.С., Игнатенко М.А., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Турманидзе Г.Н., Сорокин В.В., Степанов К.С., Игнатенко М.А.</copyright-holder><copyright-holder xml:lang="en">Turmanidze G.N., Sorokin V.V., Stepanov K.S., Ignatenko M.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.pharmjournal.ru/jour/article/view/1605">https://www.pharmjournal.ru/jour/article/view/1605</self-uri><abstract><sec><title>Введение</title><p>Введение. Совершенствование технологий выделения и очистки биологически активных веществ из растительного сырья – важная задача для фармацевтической, пищевой и косметической отраслей промышленности. Разработка технологий зачастую требует внесения изменений в конструкцию существующего оборудования. При модернизации оборудования для реализации новых технологий возможна доработка его конфигурации, позволяющая с минимальными затратами значительно повышать выход активных веществ. Для повышения эффективности процесса выделения гесперидина из растительного сырья нами предложен ряд технологических решений. В частности, предложено использовать перемешивающие устройства с конфигурацией импеллеров, разработанных на основе методов вычислительной гидродинамики, а при применении экстрактора Сокслета – обогреваемую экстракционную камеру, полученную путем добавления внешней змеевиковой рубашки, позволяющей регулировать температуру внутри экстракционной камеры для ускорения процессов диффузии и массообмена, а растворитель и экстрагент выбирать на основе термодинамических моделей расчетным способом.</p></sec><sec><title>Цель</title><p>Цель. Совершенствование технологии выделения и очистки гесперидина из растительного сырья с использованием модернизированного оборудования.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. Моделирование распределения потоков в экстракционных аппаратах осуществляли с помощью методов вычислительной гидродинамики. Для оценки результатов, полученных на основе моделирования, проводили ряд экспериментов, объектом для которых служила кожура апельсина (высушенные флаведо и альбедо, степень измельчения – 0,1–0,2 мм, влажность – 3,5 %). Количественное содержание комплекса флавоноидов в пересчете на гесперидин определяли методом прямой спектрофотометрии при длине волны 290 нм, количественное содержание гесперидина определяли гравиметрически. Статистическую обработку данных проводили с использованием программного обеспечения Minitab v21 (Minitab Inc., США), различия считали статистически значимыми при р &lt; 0,05.</p></sec><sec><title>Результаты и обсуждения</title><p>Результаты и обсуждения. На основе методов вычислительной гидродинамики для интенсификации процессов перемешивания и растворения на стадиях предварительного обезжиривания сырья и экстрагирования спроектирован шестилопастный импеллер, позволяющий ускорить процессы за счет создания осевых и радиальных потоков движения жидкости в емкостном аппарате и поддержания сырья во взвешенном состоянии в объеме жидкости при малых скоростях перемешивания и низком потреблении электроэнергии. Оснащение экстракционной камеры змеевиковой рубашкой позволило значительно повысить растворимость активного вещества и извлекать больше целевого компонента за один экстракционный цикл. Разработана технология выделения и очистки гесперидина, определены и оптимизированы параметры проведения процессов.</p></sec><sec><title>Заключение</title><p>Заключение. В результате исследования показано, что возможно интенсифицировать процессы экстракции и растворения активных веществ путем подбора перемешивающих устройств методом вычислительной гидродинамики. Для выделения плохо растворимых соединений из плотного сырья (корни, кора и пр.) предложена модификация аппарата Сокслета с обогреваемой экстракционной камерой. Модернизация типовых технологических установок позволила получить субстанцию гесперидина с выходом до 95 % и чистотой до 90 % при однократной перекристаллизации.  </p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Introduction</title><p>Introduction. Improving the technologies for isolating and purifying biologically active substances from plant materials is an important task for the pharmaceutical, food and cosmetic industries. Technology development often requires changes to the design of existing equipment. During the modernization of equipment for the implementation of new technologies, it is possible to improve its configuration, which makes it possible to significantly increase the yield of active substances at minimal cost. To increase the efficiency of the process of isolating hesperidin from plant materials, we proposed to use a number of technological solutions. In particular, it is proposed to use mixing devices with the configuration of impellers obtained by computational fluid dynamics, when using a Soxhlet extractor to use a heated extraction chamber, by adding an external coil jacket, which makes it possible to regulate the temperature inside the extraction chamber to accelerate the processes of diffusion and mass transfer, and to select the solvent and extractant on the basis of thermodynamic models by calculation.</p></sec><sec><title>Aim</title><p>Aim. Improving the technology for isolating and purifying hesperidin from plant materials using modernized equipment.</p></sec><sec><title>Materials and methods</title><p>Materials and methods. Flow distribution in extraction apparatuses was modeled using computational fluid dynamics methods. To evaluate the results obtained on the basis of modeling, a number of experiments were carried out, the object of which was the peel of an orange (dried flavedo and albedo, grinding degree 0.1–0.2 mm, moisture content 3.5 %). The quantitative content of the flavonoid complex in terms of hesperidin was determined by direct spectrophotometry at a wavelength of 290 nm, the quantitative content of hesperidin was determined gravimetrically. Statistical data processing was performed using Minitab v21 software (Minitab Inc., USA), differences were considered statistically significant at p &lt; 0.05.</p></sec><sec><title>Results and discussion</title><p>Results and discussion. Based on the methods of computational fluid dynamics, to intensify the processes of mixing and dissolution at the stages of preliminary degreasing of raw materials and extraction, a six-bladed impeller was designed, which makes it possible to accelerate these processes by creating axial and radial flows of fluid movement in a capacitive apparatus and maintaining raw materials in suspended state in the volume of liquid at low mixing speeds and energy consumption. Equipping the extraction chamber with a coiled jacket made it possible to significantly increase the solubility of the active substance and extract more of the target component in one extraction cycle. A technology for the isolation and purification of hesperidin was developed, and the parameters of the processes were determined and optimized.</p></sec><sec><title>Conclusion</title><p>Conclusion. As a result of the study, it was shown that it is possible to intensify the processes of extraction and dissolution of active substances by selecting mixing devices using the method of computational fluid dynamics. To isolate poorly soluble compounds from dense raw materials (roots, bark, etc.), a modification of the Soxhlet apparatus with a heated extraction chamber was proposed. Modernization of typical technological units made it possible to obtain the substance of hesperidin with a yield of up to 95 % and a purity of up to 90 % with a single recrystallization.  </p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>гесперидин</kwd><kwd>растворимость</kwd><kwd>оборудование</kwd><kwd>мацерация</kwd><kwd>Сокслет</kwd><kwd>обезжиривание</kwd><kwd>экстракция</kwd></kwd-group><kwd-group xml:lang="en"><kwd>hesperidin</kwd><kwd>solubility</kwd><kwd>equipment</kwd><kwd>maceration</kwd><kwd>Soxhlet</kwd><kwd>degreasing</kwd><kwd>extraction</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Результаты работы получены с использованием оборудования ЦКП «Аналитический центр ФГБОУ ВО СПХФУ Минздрава России» в рамках соглашения № 075-15-2021-685 от 26 июля 2021 года при финансовой поддержке Минобрнауки России.</funding-statement><funding-statement xml:lang="en">The results of the work were obtained using the equipment of the Center for Collective Use "Analytical Center of Saint-Petersburg State Chemical and Pharmaceutical University" within the framework of agreement No. 075-15-2021-685 dated July 26, 2021 with the financial support of the Ministry of Education and Science of Russia.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Syahputra R. A., Harahap U., Dalimunthe A., Nasution M. P., Satria D. The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review. Molecules. 2022;27(4):1320. DOI: 10.3390/molecules27041320.</mixed-citation><mixed-citation xml:lang="en">Syahputra R. A., Harahap U., Dalimunthe A., Nasution M. P., Satria D. The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review. Molecules. 2022;27(4):1320. DOI: 10.3390/molecules27041320.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Li C., Schluesener H. Health-promoting effects of the citrus flavanone hesperidin. Critical Reviews in Food Science and Nutrition. 2017;57(3):613–631. DOI: 10.1080/10408398.2014.906382.</mixed-citation><mixed-citation xml:lang="en">Li C., Schluesener H. Health-promoting effects of the citrus flavanone hesperidin. Critical Reviews in Food Science and Nutrition. 2017;57(3):613–631. DOI: 10.1080/10408398.2014.906382.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Jiang Q., Charoensiddhi S., Xue X., Sun B., Liu Y., El-Seedi H. R., Wang K. A review on the gastrointestinal protective effects of tropical fruit polyphenols. Critical Reviews in Food Science and Nutrition. 2023;63(24):7197–7223. DOI: 10.1080/10408398.2022.2145456.</mixed-citation><mixed-citation xml:lang="en">Jiang Q., Charoensiddhi S., Xue X., Sun B., Liu Y., El-Seedi H. R., Wang K. A review on the gastrointestinal protective effects of tropical fruit polyphenols. Critical Reviews in Food Science and Nutrition. 2023;63(24):7197–7223. DOI: 10.1080/10408398.2022.2145456.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Tirado-Kulieva V. A., Hernández-Martínez E., Choque-Rivera T. J., Phenolic compounds versus SARS-CoV-2: An update on the main findings against COVID-19. Heliyon. 2022;8(9):e10702. DOI: 10.1016/j.heliyon.2022.e10702.</mixed-citation><mixed-citation xml:lang="en">Tirado-Kulieva V. A., Hernández-Martínez E., Choque-Rivera T. J., Phenolic compounds versus SARS-CoV-2: An update on the main findings against COVID-19. Heliyon. 2022;8(9):e10702. DOI: 10.1016/j.heliyon.2022.e10702.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Zheng W., Wu F., Luo X., Bian C., Zhang Y., Yin F., Liu H., Fu Y. Separation of Citrus Essential Oil and Hesperidin from Citrus Peel Through Combined Mixed-Solvent and Multi-Phase Salting Out Extraction. Journal of Essential Oil Bearing Plants. 2022;25(4):899–909. DOI: 10.1080/0972060X.2022.2113147.</mixed-citation><mixed-citation xml:lang="en">Zheng W., Wu F., Luo X., Bian C., Zhang Y., Yin F., Liu H., Fu Y. Separation of Citrus Essential Oil and Hesperidin from Citrus Peel Through Combined Mixed-Solvent and Multi-Phase Salting Out Extraction. Journal of Essential Oil Bearing Plants. 2022;25(4):899–909. DOI: 10.1080/0972060X.2022.2113147.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Kim J.-W., Ko H. C., Jang M.-G., Han S. H., Kim H. J., Kim S.-J. Phytochemical content and antioxidant activity in eight citrus cultivars grown in Jeju Island according to harvest time. International Journal of Food Properties. 2023;26(1):14–23. DOI: 10.1080/10942912.2022.2151620.</mixed-citation><mixed-citation xml:lang="en">Kim J.-W., Ko H. C., Jang M.-G., Han S. H., Kim H. J., Kim S.-J. Phytochemical content and antioxidant activity in eight citrus cultivars grown in Jeju Island according to harvest time. International Journal of Food Properties. 2023;26(1):14–23. DOI: 10.1080/10942912.2022.2151620.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Ichim M. C., Scotti F., Booker A. Quality evaluation of commercial herbal products using chemical methods. Critical Reviews in Food Science and Nutrition. 2022:1–21. DOI: 10.1080/10408398.2022.2140120.</mixed-citation><mixed-citation xml:lang="en">Ichim M. C., Scotti F., Booker A. Quality evaluation of commercial herbal products using chemical methods. Critical Reviews in Food Science and Nutrition. 2022:1–21. DOI: 10.1080/10408398.2022.2140120.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Peng Q., Zhang Y., Zhu M., Bao F., Deng J., Li W. Polymethoxyflavones from citrus peel: advances in extraction methods, biological properties, and potential applications. Critical Reviews in Food Science and Nutrition. 2022:1–13. DOI: 10.1080/10408398.2022.2156476.</mixed-citation><mixed-citation xml:lang="en">Peng Q., Zhang Y., Zhu M., Bao F., Deng J., Li W. Polymethoxyflavones from citrus peel: advances in extraction methods, biological properties, and potential applications. Critical Reviews in Food Science and Nutrition. 2022:1–13. DOI: 10.1080/10408398.2022.2156476.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Zhou P., Zheng M., Li X., Zhou J., Shang Y., Li Z., Qu L. A consecutive extraction of pectin and hesperidin from Citrus aurantium L.: Process optimization, extract mechanism, characterization and bio-activity analysis. Industrial Crops and Products. 2022;182:114849. DOI: 10.1016/j.indcrop.2022.114849.</mixed-citation><mixed-citation xml:lang="en">Zhou P., Zheng M., Li X., Zhou J., Shang Y., Li Z., Qu L. A consecutive extraction of pectin and hesperidin from Citrus aurantium L.: Process optimization, extract mechanism, characterization and bio-activity analysis. Industrial Crops and Products. 2022;182:114849. DOI: 10.1016/j.indcrop.2022.114849.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Sanches V. L., de Souza Mesquita L. M., Viganó J., Contieri L. S., Pizani R., Chaves J., da Silva L. C., de Souza M. C., Breitkreitz M. C., Rostagno M. A. Insights on the Extraction and Analysis of Phenolic Compounds from Citrus Fruits: Green Perspectives and Current Status. Critical Reviews in Analytical Chemistry. 2022:1–27. DOI: 10.1080/10408347.2022.2107871.</mixed-citation><mixed-citation xml:lang="en">Sanches V. L., de Souza Mesquita L. M., Viganó J., Contieri L. S., Pizani R., Chaves J., da Silva L. C., de Souza M. C., Breitkreitz M. C., Rostagno M. A. Insights on the Extraction and Analysis of Phenolic Compounds from Citrus Fruits: Green Perspectives and Current Status. Critical Reviews in Analytical Chemistry. 2022:1–27. DOI: 10.1080/10408347.2022.2107871.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Белокуров С. С., Флисюк Е. В., Смехова И. Е. Выбор метода экстрагирования для получения извлечений из семян пажитника сенного с высоким содержанием биологически активных веществ. Разработка и регистрация лекарственных средств. 2019;8(3):35–39.</mixed-citation><mixed-citation xml:lang="en">Belokurov S. S., Flysyuk E. V., Smekhova I. E. Choice of extraction method for receiving extraction from seeds of payne hay with the high content of biologically active substances. Drug development &amp; registration. 2019;8(3):35–39. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Oliveira A. M. B., Viganó J., Sanches V. L., Rostagno M. A., Martínez J. Extraction of potential bioactive compounds from industrial Tahiti lime (Citrus latifólia Tan.) by-product using pressurized liquids and ultrasound-assisted extraction. Food Research International. 2022;157:111381. DOI: 10.1016/j.foodres.2022.111381.</mixed-citation><mixed-citation xml:lang="en">Oliveira A. M. B., Viganó J., Sanches V. L., Rostagno M. A., Martínez J. Extraction of potential bioactive compounds from industrial Tahiti lime (Citrus latifólia Tan.) by-product using pressurized liquids and ultrasound-assisted extraction. Food Research International. 2022;157:111381. DOI: 10.1016/j.foodres.2022.111381.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Государственная Фармакопея Российской Федерации XIV издания. Т. 1. М.: ФЭМБ; 2018. 1814 с.</mixed-citation><mixed-citation xml:lang="en">State Pharmacopeia of the Russian Federation XIV edition. Volume 1. Moscow: FEMB; 2018. 1814 p. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Бубенчиков Р. А., Саканян Е. И., Зубкова Н. В., Добрынин В. П., Горяинов С. В., Хажжар Ф., Платонов Е. А., Писарев Д. И., Абрамович Р. А. Разработка и валидация методики количественного определения остаточных органических растворителей в препаратах аллергенов методом ГЖХ. Разработка и регистрация лекарственных средств. 2022;11(2):159–168. DOI: 10.33380/2305-2066-2022-11-2-159-168</mixed-citation><mixed-citation xml:lang="en">Bubenchikov R. A., Sakanyan E. I., Zubkova N. V., Dobrynin V. P., Goriainov S. V., Hajjar F., Platonov E. A., Pisarev D. I., Abramovich R. A. Development and Validation of a Procedure for the Quantitative Determination of Residual Organic Solvents in Allergen Preparations by GC. Drug development &amp; registration. 2022;11(2):159–168. (In Russ.) DOI: 10.33380/2305-2066-2022-11-2-159-168</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Вайнштейн В. А., Каухова И. Е., Амелина П. С., Колдашова Ю. А., Минина С. А., Иванова А. В. Полиэкстракция травы эхинацеи системами экстрагентов с возрастающей полярностью. Разработка и регистрация лекарственных средств. 2018;(3):54–63.</mixed-citation><mixed-citation xml:lang="en">Vainshtein V. A., Kauhova I. E., Amelina P. S., Koldashova Yu. A., Minina S. A., Ivanova A. V. Polyextraction of herbs of echinacea by systems of extracents with rising polarity. Drug development &amp; registration. 2018;(3):54–63. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Чистова Ю. И. Определение оптимальных условий экстракции сбора одуванчика лекарственного травы и лопуха большого листа методами математического планирования многофакторного эксперимента. Разработка и регистрация лекарственных средств. 2019;8(1):24–28. DOI: 10.33380/2305-2066-2019-8-1-24-28.</mixed-citation><mixed-citation xml:lang="en">Chistova Yu. I. Determination of the optimal extraction conditions of dandelion herb and large burdock leaf specie by methods of mathematical planning of a multifactorial experiment. Drug development &amp; registration. 2019;8(1):24–28. (In Russ.) DOI: 10.33380/2305-2066-2019-8-1-24-28.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Pyrzynska K. Hesperidin: A Review on Extraction Methods, Stability and Biological Activities. Nutrients. 2022;14(12):2387. DOI: 10.3390/nu14122387.</mixed-citation><mixed-citation xml:lang="en">Pyrzynska K. Hesperidin: A Review on Extraction Methods, Stability and Biological Activities. Nutrients. 2022;14(12):2387. DOI: 10.3390/nu14122387.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Zhou P., Li X., Zhou J., Yang Y., Zhi J., Shen L. Mass transfer mechanism of the multivariate consecutive extraction process of pectin and hesperidin from Citrus aurantium L.: Kinetics, thermodynamics, diffusion and mass transfer coefficients. Separation and Purification Technology. 2023;311:123339. DOI: 10.1016/j.seppur.2023.123339.</mixed-citation><mixed-citation xml:lang="en">Zhou P., Li X., Zhou J., Yang Y., Zhi J., Shen L. Mass transfer mechanism of the multivariate consecutive extraction process of pectin and hesperidin from Citrus aurantium L.: Kinetics, thermodynamics, diffusion and mass transfer coefficients. Separation and Purification Technology. 2023;311:123339. DOI: 10.1016/j.seppur.2023.123339.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Каухова И. Е., Новикова Е. К., Чачин Д. А. Разработка условий экстрагирования череды трехраздельной травы, золотарника канадского травы, репешка обыкновенного травы. Разработка и регистрация лекарственных средств. 2018;(3):64–67.</mixed-citation><mixed-citation xml:lang="en">Kaukhova I. E., Novikova E. K., Chachin D. A. The development conditions for extraction of the Bidens tripartita L., Solidago canadensis L. and Agrimonia eupatoria L. herbs. Drug development &amp; registration. 2018;(3):64–67. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Chen L., Zhu S., Wang C., Chen L. Development of a HPLC-UV Method for the Separation and Quantification of Hesperidin, Neohesperidin, Neohesperidin Dihydrochalcone and Hesperetin. Natural Product Research. 2023;37(10):1714–1718. DOI: 10.1080/14786419.2022.2104275.</mixed-citation><mixed-citation xml:lang="en">Chen L., Zhu S., Wang C., Chen L. Development of a HPLC-UV Method for the Separation and Quantification of Hesperidin, Neohesperidin, Neohesperidin Dihydrochalcone and Hesperetin. Natural Product Research. 2023;37(10):1714–1718. DOI: 10.1080/14786419.2022.2104275.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
