RU2012144392A - Композиции липидных везикул и способы применения - Google Patents

Композиции липидных везикул и способы применения Download PDF

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RU2012144392A
RU2012144392A RU2012144392/15A RU2012144392A RU2012144392A RU 2012144392 A RU2012144392 A RU 2012144392A RU 2012144392/15 A RU2012144392/15 A RU 2012144392/15A RU 2012144392 A RU2012144392 A RU 2012144392A RU 2012144392 A RU2012144392 A RU 2012144392A
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lipid
vesicle
multilayer
functionalized
agent
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RU2595872C2 (ru
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Даррелл Дж. ИРВИН
Яахун МУН
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Массачусетс Интитут Оф Текнолоджи
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Abstract

1. Многослойная липидная везикула, имеющая сшивки между липидными бислоями.2. Многослойная липидная везикула по п.1, причем везикула содержит функционализированный липид.3. Многослойная липидная везикула по п.1 или 2, причем везикула содержит фосфохолин.4. Многослойная липидная везикула по п.1 или 2, причем везикула содержит глицерофосфат.5. Многослойная липидная везикула по п.2, в которой функционализированным липидом является малеимид-функционализированный липид.6. Многослойная липидная везикула по п.1, причем везикула содержит средство.7. Многослойная липидная везикула по п.6, в которой средством является профилактическое средство, терапевтическое средство или диагностическое средство.8. Многослойная липидная везикула по п.6, в которой средством является антиген.9. Многослойная липидная везикула по п.6, в которой средством является адъювант.10. Многослойная липидная везикула по п.6, в которой средством является белок.11. Многослойная липидная везикула по п.6, причем средство инкапсулировано в везикулу.12. Многослойная липидная везикула по п.6 или 11, в которой средство инкапсулировано между липидными бислоями.13. Многослойная липидная везикула по п.1 или 2, причем везикула конъюгирована с полиэтиленгликолем (PEG).14. Многослойная липидная везикула по п.1 или 2, причем везикула содержит DOPC, DOPG и малеимид-функционализированный липид.15. Многослойная липидная везикула по п.14, в которой малеимид-функционализированным липидом является малеимид-функционализированный фосфоэтаноламин.16. Композиция, содержащая многослойную липидную везикулу по любому из пп.1-15 и фармацевтически приемлемый носитель.17. Композиция, содержащая многосл�

Claims (52)

1. Многослойная липидная везикула, имеющая сшивки между липидными бислоями.
2. Многослойная липидная везикула по п.1, причем везикула содержит функционализированный липид.
3. Многослойная липидная везикула по п.1 или 2, причем везикула содержит фосфохолин.
4. Многослойная липидная везикула по п.1 или 2, причем везикула содержит глицерофосфат.
5. Многослойная липидная везикула по п.2, в которой функционализированным липидом является малеимид-функционализированный липид.
6. Многослойная липидная везикула по п.1, причем везикула содержит средство.
7. Многослойная липидная везикула по п.6, в которой средством является профилактическое средство, терапевтическое средство или диагностическое средство.
8. Многослойная липидная везикула по п.6, в которой средством является антиген.
9. Многослойная липидная везикула по п.6, в которой средством является адъювант.
10. Многослойная липидная везикула по п.6, в которой средством является белок.
11. Многослойная липидная везикула по п.6, причем средство инкапсулировано в везикулу.
12. Многослойная липидная везикула по п.6 или 11, в которой средство инкапсулировано между липидными бислоями.
13. Многослойная липидная везикула по п.1 или 2, причем везикула конъюгирована с полиэтиленгликолем (PEG).
14. Многослойная липидная везикула по п.1 или 2, причем везикула содержит DOPC, DOPG и малеимид-функционализированный липид.
15. Многослойная липидная везикула по п.14, в которой малеимид-функционализированным липидом является малеимид-функционализированный фосфоэтаноламин.
16. Композиция, содержащая многослойную липидную везикулу по любому из пп.1-15 и фармацевтически приемлемый носитель.
17. Композиция, содержащая многослойную липидную везикулу по любому из пп.1-15 и вспомогательное вещество, приемлемое для лиофилизации.
18. Композиция, содержащая многослойную липидную везикулу по п.17, в которой вспомогательное вещество, приемлемое для лиофилизации, содержит сахарозу.
19. Способ, включающий
контактирование липосом, содержащих функционализированный липид, с двухвалентным катионом с образованием слитых липосом и
контактирование слитых липосом со сшивателем с образованием многослойных липидных везикул, имеющих сшивки между липидными бислоями.
20. Способ по п.19, в котором функционализированным липидом является малеимид-функционализированный липид.
21. Способ по п.19 или 20, в котором липосомы содержат фосфохолин.
22. Способ по п.19 или 20, в котором липосомы содержат глицерофосфат.
23. Способ по п.19, в котором липосомы содержат малеимид-функционализированный липид, фосфохолин и глицерофосфат.
24. Способ по п.19 или 20, в котором функционализированным липидом является функционализированный фосфоэтаноламин.
25. Способ по п.23, в котором малеимид-функционализированным липидом является малеимид-функционализированный фосфоэтаноламин.
26. Способ по п.19 или 20, в котором сшивателем является дитиоловый сшиватель.
27. Способ по п.19 или 20, в котором сшивателем является дитиотреитол (DTT).
28. Способ по п.19 или 20, дополнительно включающий конъюгирование полиэтиленгликоля (PEG) с поверхностью многослойных липидных везикул, имеющих сшивки между липидными бислоями.
29. Способ по п.19 или 20, в котором двухвалентными катионами являются Са2+.
30. Способ по п.19 или 20, в котором двухвалентными катионами являются Mg2+.
31. Способ по п.19 или 20, в котором контактирование происходит в водном буфере.
32. Способ по п.19 или 20, в котором липосомы содержат средство.
33. Способ по п.32, в котором средством является профилактическое средство, терапевтическое средство или диагностическое средство.
34. Способ по п.19 или 20, в котором липосомы получены с использованием DOPC, DOPG и малеимид-функционализированного липида в мольном отношении 40:10:50.
35. Способ по п.19 или 20, в котором мольное отношение дитиолового сшивателя к малеимид-функционализированному липиду составляет 1:2.
36. Способ, включающий
контактирование многослойной липидной везикулы, содержащей функционализированный липид, со сшивателем с образованием многослойных липидных везикул, имеющих сшивки между липидными бислоями.
37. Способ, включающий
введение субъекту многослойной липидной везикулы, имеющей сшитые липидные бислои, которая содержит средство в эффективном количестве.
38. Способ по п.37, в котором многослойная липидная везикула содержит биоразлагаемый липид.
39. Способ по п.37 или 38, в котором многослойная липидная везикула содержит фосфолипид.
40. Способ по п.37 или 38, в котором многослойная липидная везикула содержит фосфохолин, глицерофосфат и/или фосфоэтаноламин.
41. Способ по п.37 или 38, в котором многослойная липидная везикула содержит функционализированный липид.
42. Способ по п.41, в котором функционализированным липидом является малеимид-функционализированный липид.
43. Способ по п.42, в котором малеимид-функционализированным липидом является малеимид-функционализированный фосфоэтаноламин.
44. Способ по п.37 или 38, в котором средством является профилактическое средство.
45. Способ по п.37 или 38, в котором средством является терапевтическое средство.
46. Способ по п.37 или 38, в котором средством является антиген.
47. Способ по п.37 или 38, в котором средством является адъювант.
48. Способ по п.37 или 38, в котором многослойная липидная везикула содержит более чем одно средство.
49. Способ по п.37 или 38, в котором многослойная липидная везикула содержит два средства.
50. Способ по п.49, в котором многослойная липидная везикула содержит антиген и адъювант.
51. Способ по п.37 или 38, в котором многослойная липидная везикула конъюгирована с PEG на своей внешней поверхности.
52. Способ, включающий
контактирование многослойной липидной везикулы, имеющей сшитые липидные бислои, которая содержит средство, с клеткой in vitro.
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US8747869B2 (en) 2014-06-10
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