danДоклады Национальной академии наук БеларусиDoklady of the National Academy of Sciences of Belarus1561-83232524-2431The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"dan-473Research ArticleХИМИЯCHEMISTRYПОЛУЧЕНИЕ КОМПЛЕКСНЫХ ПРЕПАРАТОВ НА ОСНОВЕ ЛИПОСОМАЛЬНОЙ ФОРМЫ СТРЕПТОКИНАЗЫ И ИХ ФАРМАКОКИНЕТИЧЕСКИЕ ХАРАКТЕРИСТИКИPREPARATION OF COMPLEX FORMULATIONS BASED ON LIPOSOMAL STREPTOKINASE AND THEIR PHARMACOKINETIC CHARACTERISTICSДубатовкаЕ. И.DubatoukaKatsiaryna I.

мл. науч. сотрудник

ул. Ф. Скорины, 36, 220141

Junior researcher

36, F. Skoryna Str., 220141

d_katerina@tut.byЛутикИ. Л.LutsikIryna L.

мл. науч. сотрудник

ул. П. Бровки, 3/3, 220013

Junior researcher

3/3, P. Brovka Str., 220013

lutik-irinka@yandex.byЧернявскийЕ. А.CherniavskyEvgenii A.

канд. хим. наук, заместитель директора

ул. Ленинградская, 14, 220030

Ph. D. (Chemistry), Deputy Director

14, Leningradskaya Str., 220030

eugene.cherniavsky@gmail.comБондаренкоЕ. С.BondarenkoEkaterina S.

мл. науч. сотрудник

ул. Ленинградская, 14, 220030

Junior researcher

14, Leningradskaya Str., 220030

АдзерихоИ. Э.AdzerikhoIgor E.

д-р мед. наук, профессор

ул. П. Бровки, 3/3, 220013

D. Sc. (Medicine), Professor

3/3, P. Brovka Str., 220013

adzerikhoigor@mail.ruАгабековВ. Е.AgabekovVladimir E.

академик, д-р хим. наук, профессор, директор

ул. Ф. Скорины, 36, 220141

Academician, D. Sc. (Chemistry), Professor, Director

36, F. Skoryna Str., 220141

agabekov@ichnm.basnet.byИнститут химии новых материалов Национальной академии наук Беларуси, МинскInstitute of Chemistry of New Materials of the National Academy of Sciences of Belarus, MinskБелорусская медицинская академия последипломного образования, МинскBelarussian Medical Academy of Postgraduate Education, MinskНаучно-исследовательский институт физико-химических проблем Белорусского государственного университета, МинскResearch Institute for Physical Chemical Problems of the Belarusian State University, Minsk2017210120186165057Copyright © Дубатовка Е.И., Лутик И.Л., Чернявский Е.А., Бондаренко Е.С., Адзерихо И.Э., Агабеков В.Е., 20182018Дубатовка Е.И., Лутик И.Л., Чернявский Е.А., Бондаренко Е.С., Адзерихо И.Э., Агабеков В.Е.Dubatouka K.I., Lutsik I.L., Cherniavsky E.A., Bondarenko E.S., Adzerikho I.E., Agabekov V.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://doklady.belnauka.by/jour/article/view/473

Получена липосомальная форма стрептокиназы (СК) с гидродинамическим диаметром ~70 нм, дзета-потенциалом –6,2 мВ и степенью включения вещества 14,1 %, на основе которой приготовлены комплексные препараты, содержащие «связанную» и «свободную» СК в соотношениях 20/80, 40/60 и 50/50. Для них в эксперименте in vivo на крысах показано увеличение периода полувыведения от 1,8 до 31,9 мин и времени достижения максимальной концентрации стрептокиназы от 15 до 45 мин, а также уменьшение константы элиминации в ~18 раз по сравнению с нативной СК. Оптимальное соотношение «связанной» и «свободной» СК в комплексном препарате составило 40 и 60 % соответственно, что было использовано для получения липосомальной фибрин-специфичной формы тромболитика, который обладает практически такими же физико-химическими и фармакокинетическими параметрами. 

It was obtained that liposomal streptokinase (SK) with a hydrodynamic diameter of ~70 nm and a zeta-potential of –6.2 mV contains 14.1 % wt of drug. The complex formulations based on liposomal SK include “associated” and “free” SK in the ratios of 20/80, 40/60 and 50/50. The in vivo experiments on rats showed an increase in the elimination half-time from 1.8 to 31.9 min and in the time to reach the maximum concentration of streptokinase from 15 to 45 min. The decrease in the elimination rate constant by a factor of 18 compared with SK was also found. The optimal ratio of “associated” and “free” SK in the complex formulation was 40 and 60 % respectively. It was used to obtain liposomal fibrin-specific form of thrombolytic with similar physico-chemical and pharmacokinetic parameters. 

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