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RU2017126610A - Терапевтические композиции и способы против злокачественных опухолей с молекулами рнки, направленными против hsp47 - Google Patents

Терапевтические композиции и способы против злокачественных опухолей с молекулами рнки, направленными против hsp47 Download PDF

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RU2017126610A
RU2017126610A RU2017126610A RU2017126610A RU2017126610A RU 2017126610 A RU2017126610 A RU 2017126610A RU 2017126610 A RU2017126610 A RU 2017126610A RU 2017126610 A RU2017126610 A RU 2017126610A RU 2017126610 A RU2017126610 A RU 2017126610A
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malignant tumor
hsp47
introduction
rnai molecules
composition
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RU2017126610A
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RU2756253C2 (ru
RU2017126610A3 (ru
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Венбин ИН
Акихиро ЙОНЕДА
Ясуаки ТАМУРА
Кендзироу МИНОМИ
Бхарат МАДЖЕТИ
Цзихуа ЛЮ
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Нитто Денко Корпорейшн
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Claims (32)

1. Фармацевтическая композиция для лечения злокачественной опухоли, включающая наночастицы, инкапсулирующие молекулы РНКи, где молекулы РНКи направлены против Hsp47.
2. Фармацевтическая композиция по п.1, где композиция сохраняет по меньшей мере 80% активности инкапсулированных молекул РНКи после воздействия человеческой сыворотки в течение 1 часа.
3. Фармацевтическая композиция по п.1, где молекулами РНКи для лечения злокачественной опухоли являются молекулы миРНК или мшРНК.
4. Фармацевтическая композиция по п.1, где каждая молекула РНКи включает двухцепочечную область, где двухцепочечная область включает нуклеотидную последовательность, соответствующую последовательности-мишени в мРНК Hsp47.
5. Способ передачи действующего вещества субъекту для лечения злокачественной опухоли, включающий введение субъекту фармацевтической композиции по п.1.
6. Способ предотвращения, лечения или уменьшения тяжести одного или более симптомов злокачественной опухоли у нуждающегося в этом млекопитающего, включающий введение млекопитающему терапевтически эффективного количества композиции, включающей молекулы РНКи, активные при снижении экспрессии Hsp47.
7. Способ по п.6, где млекопитающим является человек, Hsp47 является человеческим Hsp47.
8. Способ по п.6, где злокачественная опухоль оверэкспрессирует Hsp47.
9. Способ по п.6, где молекулы РНКи уменьшают экспрессию Hsp47 у млекопитающего.
10. Способ по п.6, где введение снижает экспрессию Hsp47 у млекопитающего по меньшей мере на 5% в течение по меньшей мере 5 дней.
11. Способ по п.6, где введение уменьшает объем злокачественной опухоли у млекопитающего по меньшей мере на 5% или по меньшей мере на 10%, или по меньшей мере на 20%, или по меньшей мере на 30%, или по меньшей мере на 40%, или по меньшей мере на 50%.
12. Способ по п.6, где способ уменьшает один или более симптомов злокачественной опухоли или задерживает, или останавливает прогрессирование злокачественной опухоли.
13. Способ по п.6, где введение уменьшает рост клеток злокачественной опухоли у субъекта.
14. Способ по п.6, где введение уменьшает рост клеток злокачественной опухоли у субъекта по меньшей мере на 2% или по меньшей мере на 5%, или по меньшей мере на 10%, или по меньшей мере на 15%, или по меньшей мере на 20%.
15. Способ по п.6, где опухолевые клетки оверэкспрессируют РНК или белок Hsp47 дикого типа.
16. Способ по п.6, где опухоль является саркомой, выбранной из группы, состоящей из аденокарциномы легкого, муцинозной аденомы, протоковой карциномы поджелудочной железы и карциномы толстой и прямой кишки.
17. Способ по п.6, где злокачественная опухоль является саркомой, выбранной из группы аденокарциномы легкого, муцинозной аденомы, протоковой карциномы поджелудочной железы, карциномы толстой и прямой кишки, рака молочной железы и фибросаркомы.
18. Способ по п.6, где злокачественная опухоль расположена в анатомической области, выбранной из группы легкого, печени, поджелудочной железы, толстой кишки, почки, сердца, кости, кожи, кишечника и суставов, а также их любой комбинации.
19. Способ по п.6, где введение производят от 1 до 12 раз в день.
20. Способ по п.6, где введение производят в течение 1, 2, 3, 4, 5, 6 или 7 дней.
21. Способ по п.6, где введение производят в течение 1,2,3,4, 5,6, 8, 10 или 12 недель.
22. Способ по п.6, где введение производят в дозе от 0,01 до 2 мг/кг молекул РНКи, по меньшей мере один раз в день в течение периода продолжительностью до двенадцати недель.
23. Способ по п.6, где введение обеспечивает среднюю AUC(0-last) от 1 до 1000 мкг*мин/мл и среднюю Cmax от 0,1 до 50 мкг/мл для молекулы РНКи Hsp47.
24. Способ по п.6, где введение является внутривенной инъекцией, внутрикожной инъекцией, подкожной инъекцией, внутримышечной инъекцией, внутрибрюшинной инъекцией, пероральным, наружным, инфузией или ингаляцией.
25. Композиция для применения в лечении злокачественной опухоли у субъекта, где композиция включает липосомные наночастицы, которые инкапсулируют молекулы РНКи, направленные против Hsp47.
26. Композиция по п.25, где злокачественная опухоль расположена в легком, толстой кишке или поджелудочной железе.
27. Композиция по п.25, где злокачественная опухоль расположена в печени, сердце, кости, коже или кишечнике.
28. Композиция по п.25, где композиция включает липосомные наночастицы, имеющие размер от 10 до 1000 нм.
29. Композиция по п.25, где композиция включает липосомные наночастицы, имеющие размер от 10 до 150 нм.
30. Композиция по п.29, где липосомные наночастицы сохраняют по меньшей мере 80% инкапсулированных молекул РНКи после воздействия человеческой сыворотки в течение 1 часа.
31. Способ передачи действующего вещества в орган субъекта для лечения злокачественной опухоли, где способ включает введение субъекту композиции по п.25.
32. Способ по п.31, где злокачественная опухоль расположена в легком, толстой кишке, почке, поджелудочной железе, печени, костном мозге, коже, глазу или кишечнике.
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