RU2015122755A - Композиции и способы усиления энергетического обмена - Google Patents
Композиции и способы усиления энергетического обмена Download PDFInfo
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- RU2015122755A RU2015122755A RU2015122755A RU2015122755A RU2015122755A RU 2015122755 A RU2015122755 A RU 2015122755A RU 2015122755 A RU2015122755 A RU 2015122755A RU 2015122755 A RU2015122755 A RU 2015122755A RU 2015122755 A RU2015122755 A RU 2015122755A
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- glucose
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Claims (57)
1. Композиция, эффективная для усиления энергетического обмена, содержащая:
a) ингибитор фосфодиэстеразы 5 (PDE 5) и
b) лейцин и/или метаболит лейцина.
2. Композиция по п. 1, в котором композиция усиливает энергетический обмен у субъекта в более высокой степени по сравнению с введением субъекту компонента (a) или компонента (b) отдельно.
3. Композиция по п. 2, в котором усиленный энергетический обмен измеряют по повышению окисления жирных кислот в адипоците, по меньшей мере, примерно на 300%, повышению утилизации глюкозы в адипоците, по меньшей мере, на 150%, повышению утилизации глюкозы в адипоците в случае изменения, по меньшей мере, на 60% или увеличению митохондриальной биомассы, по меньшей мере, примерно на 15%.
4. Композиция по п. 2, в котором усиленный энергетический обмен измеряют по снижению постпрандиального уровня глюкозы в крови, по меньшей мере, на 20%, снижению постпрандиального уровня инсулина, по меньшей мере, на 30%, снижению уровня глюкозы в крови натощак, по меньшей мере, на 40%, снижению уровня инсулина натощак, по меньшей мере, на 40%, снижению ответа в виде уровня глюкозы в крови на нагрузку глюкозой, по меньшей мере, на 15%, двукратному улучшению результатов оценки толерантности к инсулину или снижению воспалительного стресса, по меньшей мере, на 20%.
5. Композиция по п. 4, в котором снижение уровня глюкозы в крови в ответ на нагрузку глюкозой подверждается площадью под кривой толерантности к глюкозе.
6. Композиция по п. 1, в котором ингибитором PDE5 является аванафил, иоденафил, мироденафил, силденафил, тадалафил, икариин, варденафил, уденафил или запринст.
7. Композиция по п. 1, в котором ингибитором PDE5 является силденафил или икариин.
8. Композиция по п. 1, в котором ингибитором PDE5 является икариин.
9. Композиция по п. 1, в котором компонентом (b) является HMB.
10. Композиция по п. 1, в котором компонентом (b) является свободный лейцин.
11. Композиция по п. 1, дополнительно содержащая неизбирательный ингибитор PDE.
12. Композиция по п. 1, дополнительно содержащая витамин B6.
13. Композиция по п. 1, дополнительно содержащая другое фармацевтически активное средство, отличное от ингибитора PDE5.
14. Композиция по п. 1, в котором композиция по существу не содержит аланина, аргинина, аспарагина, аспарагиновой кислоты, цистеина, глутаминовой кислоты, глутамина, глицина, гистидина, изолейцина, лизина, метионина, фенилаланина, пролина, серина, треонина, триптофана, тирозина или валина в форме свободной аминокислоты.
15. Композиция по п. 1, в котором композиция по существу не содержит изолейцина и валина в форме свободной аминокислоты.
16. Композиция по п. 1, в котором композиция приготовлена для перорального приема.
17. Композиция по п. 1, в котором композиция представляет собой стандартную дозу, содержащую субтерапевтическое количество компонента (a).
18. Стандартная доза по п. 17, в котором субтерапевтическое количество компонента (a) составляет примерно от 0,1 до примерно 20 мг силденафила.
19. Стандартная доза по п. 17, в котором субтерапевтическое количество компонента (a) составляет примерно от 0,1 до примерно 10 мг силденафила.
20. Стандартная доза по п. 17, в котором субтерапевтическое количество компонента (a) составляет примерно 0,5 - примерно 50 мг аванафила, примерно 0,05 - примерно 10 мг иоденафила, примерно 0,25 - примерно 25 мг мироденафила, примерно 0,01 - примерно 1,25 мг тадалафила, примерно 0,01 - примерно 1,25 мг варденафила, примерно 0,5 - примерно 50 мг уденафила, примерно 0,5 - примерно 50 мг запринста или примерно 0,05 - примерно 100 мг икариина.
21. Стандартная доза по п. 17, в котором компонент (b) содержит примерно от 50 до примерно 1000 мг свободного лейцина.
22. Стандартная доза по п. 17, в котором компонент (b) содержит примерно от 500 до примерно 700 мг свободного лейцина.
23. Стандартная доза по п. 17, в котором компонент (b) содержит, по меньшей мере, примерно 500 мг свободного лейцина.
24. Стандартная доза по п. 17, в котором компонент (b) содержит, по меньшей мере, примерно 200 мг HMB.
25. Композиция, эффективная для усиления энергетического обмена, содержащая:
a) ингибитор PDE5 и
b) полифенол,
при этом композиция усиливает энергетический обмен у субъекта в более высокой степени по сравнению с введением субъекту компонента (a) или компонента (b) отдельно.
26. Композиция по п. 25, в котором полифенолом является ресвератрол.
27. Композиция по п. 25, в котором полифенолом является стильбен или гидроксикоричная кислота.
28. Композиция по п. 25, в котором полифенолом является хлорогеновая кислота, ресвератрол, кофеиновая кислота, пикеатаннол, эллаговая кислота, галлат эпигаллокатехина (EGCG), экстракт виноградных косточек или любой их аналог.
29. Композиция по п. 25, дополнительно содержащая лейцин и/или метаболит лейцина.
30. Способ регулирования энергетического обмена у субъекта, нуждающегося в таком регулировании, включающий в себя введение субъекту композиции по любому из предшествующих пунктов.
31. Способ по п. 30, в котором композицию вводят перорально.
32. Способ регулирования энергетического обмена, включающий в себя:
a) идентификацию субъекта, имеющего или склонного к ожирению или диабету; и
b) введение субъекту композиции по любому из пп. 1-29.
33. Способ регулирования энергетического обмена у субъекта, нуждающегося в таком регулировании, включающий в себя введение субъекту стандартной дозы, содержащей субтерапевтическое количество ингибитора PDE5 и, по меньшей мере, примерно 500 мг лейцина или примерно 200 мг HMB.
34. Способ по п. 33, в котором субтерапевтическое количество ингибитора PDE5 составляет меньше чем примерно 10 мг/сутки.
35. Способ по п. 33, в котором ингибитором PDE5 является силденафил.
36. Способ усиления энергетического обмена в организме субъекта, включающий в себя:
введение указанному субъекту композиции по любому из пп. 1-29 на выбранном уровне дозы, при этом выбранный уровень дозы индуцирует у субъекта циркулирующий уровень, составляющий примерно 1 нМ силденафила и примерно 0,5 мМ лейцина.
37. Способ лечения диабета у субъекта, нуждающегося в таком лечении, включающий в себя введение субъекту терапевтически эффективной композиции, содержащей:
a) ингибитор PDE и
b) аминокислоты с разветвленной цепью в форме свободной аминокислоты или ее свободного метаболита.
38. Способ по п. 37, в котором аминокислотой с разветвленной цепью является свободный лейцин.
39. Способ по п. 37, в котором метаболитом является HMB.
40. Способ по п. 37, в котором ингибитор PDE является ингибитором PDE5.
41. Способ по п. 37, в котором ингибитором PDE5 является аванафил, иоденафил, мироденафил, силденафил, тадалафил, икариин, варденафил, уденафил или запринст.
42. Способ по п. 37, включающий в себя введение терапевтически эффективной композиции перорально.
43. Способ по п. 37, включающий в себя введение терапевтически эффективной композиции в течение, по меньшей мере, одной, двух или шести недель.
44. Способ по п. 37, в котором введение улучшает симптом диабета у субъекта.
45. Способ по п. 44, в котором улучшение симптома диабета измеряют по снижению постпрандиального уровня глюкозы в крови, по меньшей мере, на 20%, снижению постпрандиального уровня инсулина, по меньшей мере, на 30%, снижению уровня глюкозы в крови натощак, по меньшей мере, на 40%, снижению уровня инсулина натощак, по меньшей мере, на 40%, снижению уровня глюкозы в крови в ответ на нагрузку глюкозой, по меньшей мере, на 15%, двукратному улучшению результатов измерения толерантности к инсулину или снижению воспалительного стресса, по меньшей мере, на 20%.
46. Способ по п. 45, в котором снижение ответа в виде уровня глюкозы в крови на нагрузку глюкозой подтверждается по площади под кривой толерантности к глюкозе.
47. Набор, содержащий многодневный запас стандартных доз композиции по любому из пп. 1-29 и инструкции по введению указанного многодневного запаса в течение периода времени, составляющего множество дней.
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-
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- 2013-11-13 JP JP2015542039A patent/JP6469015B2/ja active Active
- 2013-11-13 SG SG10201709195TA patent/SG10201709195TA/en unknown
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- 2013-11-13 EP EP13854549.6A patent/EP2919772B1/en active Active
- 2013-11-13 US US14/442,711 patent/US9943517B2/en active Active
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- 2013-11-13 CN CN201380070248.9A patent/CN104918610B/zh not_active Expired - Fee Related
- 2013-11-13 CN CN201810199650.1A patent/CN108452311A/zh active Pending
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- 2013-11-13 AU AU2013344753A patent/AU2013344753B2/en not_active Ceased
- 2013-11-13 CA CA2891335A patent/CA2891335C/en active Active
- 2013-11-13 KR KR1020157015622A patent/KR20150082623A/ko not_active Application Discontinuation
- 2013-11-13 BR BR112015010947A patent/BR112015010947A2/pt not_active IP Right Cessation
- 2013-11-13 RU RU2015122755A patent/RU2655794C2/ru active
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WO2014078459A1 (en) | 2014-05-22 |
KR20150082623A (ko) | 2015-07-15 |
US9943517B2 (en) | 2018-04-17 |
US20200338078A1 (en) | 2020-10-29 |
US20180235970A1 (en) | 2018-08-23 |
CN104918610B (zh) | 2018-04-10 |
EP2919772A4 (en) | 2016-06-08 |
CN104918610A (zh) | 2015-09-16 |
CA2891335C (en) | 2021-05-04 |
US10646489B2 (en) | 2020-05-12 |
SG10201709195TA (en) | 2017-12-28 |
AU2018264157A1 (en) | 2018-12-06 |
US20160279130A1 (en) | 2016-09-29 |
IL238726B (en) | 2020-02-27 |
MX2015006023A (es) | 2016-03-31 |
PH12015501062A1 (en) | 2015-08-17 |
AU2013344753B2 (en) | 2018-09-27 |
AU2013344753A1 (en) | 2015-06-04 |
CN108452311A (zh) | 2018-08-28 |
EP2919772B1 (en) | 2019-03-27 |
JP2015537002A (ja) | 2015-12-24 |
IL238726A0 (en) | 2015-06-30 |
CN108295058A (zh) | 2018-07-20 |
EP2919772A1 (en) | 2015-09-23 |
SG11201503774PA (en) | 2015-06-29 |
JP6469015B2 (ja) | 2019-02-13 |
RU2655794C2 (ru) | 2018-05-29 |
HK1212594A1 (zh) | 2016-06-17 |
BR112015010947A2 (pt) | 2018-06-05 |
CA2891335A1 (en) | 2014-05-22 |
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