pharmjournalРазработка и регистрация лекарственных средствDrug development & registration2305-20662658-5049LLC «CPHA»10.33380/2305-2066-2020-9-2-24-32pharmjournal-757Research ArticleПОИСК И РАЗРАБОТКА НОВЫХ ЛЕКАРСТВЕННЫХ СРЕДСТВRESEARCH AND DEVELOPMENT OF NEW DRUG PRODUCTSВлияние дейтерия на свойства фармацевтических субстанций (обзор)The Influence of Deuterium on the Properties of Pharmaceutical Substances (Review)СыроешкинА. В.SyroeshkinA. V.

117198, г. Москва, ул. Миклухо-Маклая, д. 6

Anton V. Syroeshkin  

6, Mikluho-Maklaya str., Moscow, 117198

ЕлизароваТ. Е.ElizarovaT. E.

117198, г. Москва, ул. Миклухо-Маклая, д. 6

Tatyana E. Elizarova  

6, Mikluho-Maklaya str., Moscow, 117198

ПлетенёваТ. В.PletenevaT. V.

Плетенёва Татьяна Вадимовна – профессор кафедры фармацевтической и токсикологической химии 

117198, г. Москва, ул. Миклухо-Маклая, д. 6

 Tatyana V. Pleteneva  

6, Mikluho-Maklaya str., Moscow, 117198

tvplet@mail.ruУспенскаяЕ. В.UspenskayaE. V.

117198, г. Москва, ул. Миклухо-Маклая, д. 6

Elena V. Uspenskaya  

6, Mikluho-Maklaya str., Moscow, 117198

ЛевицкаяО. В.LevitskayaO. V.

117198, г. Москва, ул. Миклухо-Маклая, д. 6

Olga V. Levitskaya  

6, Mikluho-Maklaya str., Moscow, 117198

ЗлацкийИ. А.ZlatskiyI. A.

117198, г. Москва, ул. Миклухо-Маклая, д. 6, 

04114, Украина, Киев, ул. Вышгородская, д. 67

Igor A. Zlatskiy  

6, Mikluho-Maklaya str., Moscow, 117198, 

67, Vyshgorodska str., Kyiv, 04114, Ukraine

МаксимоваТ. В.MaksimovaT. V.

117198, г. Москва, ул. Миклухо-Маклая, д. 6

Tatyana V. Maksimova  

6, Mikluho-Maklaya str., Moscow, 117198

ФГАОУ ВО «Российский университет дружбы народов» (Российский университет дружбы народов, РУДН)Peoples Friendship University of Russia (RUDN University)ФГАОУ ВО «Российский университет дружбы народов» (Российский университет дружбы народов, РУДН); ГУ «Институт генетической и регенеративной медицины НАМН Украины»Peoples Friendship University of Russia (RUDN University); State Institute of Genetic and Regenerative Medicine NAMS of Ukraine202001042020922432Copyright © Сыроешкин А.В., Елизарова Т.Е., Плетенёва Т.В., Успенская Е.В., Левицкая О.В., Злацкий И.А., Максимова Т.В., 20202020Сыроешкин А.В., Елизарова Т.Е., Плетенёва Т.В., Успенская Е.В., Левицкая О.В., Злацкий И.А., Максимова Т.В.Syroeshkin A.V., Elizarova T.E., Pleteneva T.V., Uspenskaya E.V., Levitskaya O.V., Zlatskiy I.A., Maksimova T.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmjournal.ru/jour/article/view/757Введение

Введение. Обзор посвящен влиянию изотопа водорода – дейтерия на биологическую активность фармацевтических субстанций.

Текст

Текст. Рассмотрены два аспекта влияния дейтерия на свойства активных фармацевтических ингредиентов и вспомогательных веществ. Первый связан с использованием дейтерированных субстанций – новых соединений или полученных замещением протия в известных протиевых аналогах. Кинетический изотопный эффект (КИЭ), выражающийся в снижении скорости биотрансформации в результате дейтерирования, позволяет прогнозировать быстрое развитие нового направления в разработке лекарственных средств. При идентичном терапевтическом эффекте дейтерированные аналоги обеспечивают улучшение фармакокинетических характеристик, снижение токсичности, блокировку эпимеризации оптически активных субстанций, изменение механизмов биотрансформации. Второй аспект влияния дейтерия отражает возрастание КИЭ в процессах с участием известных фармацевтических субстанций в водных растворах с соотношением дейтерий/протий (D/H) ниже природного. Впервые на диаграмме «доза – ответ» показана идентичность дейтерия эссенциальным микроэлементам, когда недостаток и избыток элемента снижает жизнеспособность организма. Улучшенные кинетические характеристики продемонстрированы для молекулярного и организменного уровня разной иерархической градации. В частности, они заключаются в возможности увеличения скорости растворения субстанций, влияния на процессы мутаротации углеводов и оптическую активность хиральных субстанций, возрастание накопления эссенциальных элементов в лекарственных растениях и других процессах.

Заключение

Заключение. Полученные результаты позволяют прогнозировать механизмы влияния дейтерия на биохимические превращения фармацевтических субстанций в организме.

Introduction

Introduction. The study discusses the hydrogen isotope 2H effect on the biological activity of pharmaceutical substances.

Text

Text. Two aspects of the deuterium effect on the properties of active pharmaceutical ingredients and excipients are considered. The first one involves the use of deuterated substances, new compounds or substituted counterparts. Replacing protium with deuterium is used to reduce the rate of biotransformation. The kinetic isotope effect (KIE), expressed in a decrease in the rate of biotransformation as a result of deuteration, allows us to predict the rapid development of new directions in the development of pharmaceuticals. With the same therapeutic effect, an improvement in pharmacokinetic characteristics, a decrease in toxicity, a blocking of the epimerization of optically active substances, a change in the mechanisms of action are observed. The second aspect of the deuterium effect is associated with an increase in KIE of known pharmaceutical substances in aqueous solutions with a deuterium/protium ratio (D/H) lower than in natural water. For the first time, dose-response diagrams for deuterium demonstrate identity with essential microelements. There is a safety zone for the certain D/H relationship, beyond which the organism's vitality decreases. Improved kinetic characteristics are demonstrated for molecular level and for biological objects of various hierarchical levels. In particular, they include the possibility of increasing the dissolution rate of substances, the influence on the processes of mutarotation and the optical activity of chiral substances, the degree of accumulation of necessary elements in medicinal plants, and other processes.

Conclusion

Conclusion. The results make it possible to predict the mechanisms of deuterium influence on the biochemical transformations of pharmaceutical substances in the body.

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The authors declare that there are no conflicts of interest present.