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RU2005105664A - Лечение рака - Google Patents

Лечение рака Download PDF

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Publication number
RU2005105664A
RU2005105664A RU2005105664/15A RU2005105664A RU2005105664A RU 2005105664 A RU2005105664 A RU 2005105664A RU 2005105664/15 A RU2005105664/15 A RU 2005105664/15A RU 2005105664 A RU2005105664 A RU 2005105664A RU 2005105664 A RU2005105664 A RU 2005105664A
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RU
Russia
Prior art keywords
inhibitor
tumors
rapamycin
agent
pharmaceutical combination
Prior art date
Application number
RU2005105664/15A
Other languages
English (en)
Other versions
RU2325906C2 (ru
Inventor
Хейди ЛАНЕ (CH)
Хейди ЛАНЕ
Теренс О`РЕЙЛЛИ (CH)
Теренс О`РЕЙЛЛИ
Джинетта Марджори ВУД (CH)
Джинетта Марджори ВУД
Original Assignee
Новартис АГ (CH)
Новартис Аг
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26245731&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=RU2005105664(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from GB0104072A external-priority patent/GB0104072D0/en
Priority claimed from GB0124957A external-priority patent/GB0124957D0/en
Application filed by Новартис АГ (CH), Новартис Аг filed Critical Новартис АГ (CH)
Publication of RU2005105664A publication Critical patent/RU2005105664A/ru
Application granted granted Critical
Publication of RU2325906C2 publication Critical patent/RU2325906C2/ru

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
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    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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Claims (20)

1. Применение производных рапамицина формулы I
Figure 00000001
где R1 обозначает СН3 или С3-С6алкинил,
R2 обозначает Н или -СН2-СН2ОН- и
Х обозначает =O, (Н, Н) или (Н, ОН)
при условии, что R2 не обозначает Н, если Х обозначает =O и R1 обозначает СН3, для приготовления фармацевтической композиции, предназначенной для лечения плотных опухолей, представляющих собой опухоли головного мозга и другие опухоли центральной нервной системы, рак головы и/или шеи, опухоли системы кровообращения, опухоли выделительной системы, опухоли желудочно-кишечного тракта, опухоли, поражающие печень и находящиеся внутри печени желчные каналы, желчный пузырь, другие и неспецифические отделы желчного тракта, опухоли ротовой полости, опухоли репродуктивной системы, опухоли дыхательного тракта, носовой полости и среднего уха, вторичного синуса, гортани, трахеи, бронхов, опухоли скелетной системы, кожные опухоли и опухоли, поражающие другие ткани, включая периферические нервы и автономную нервную систему, соединительную и мягкую ткань, забрюшинное пространство и брюшину, глаз и прилежащие органы, щитовидную железу, надпочечник и связанные с ними структуры, злокачественный опухолевый метастаз и неспецифическую злокачественную опухоль лимфатических узлов, злокачественный опухолевый метастаз дыхательной и пищеварительной систем.
2. Применение производных рапамицина формулы I по п.1 для приготовления фармацевтической композиции, предназначенной для лечения инвазии плотных опухолей или симптомов, связанных с ростом такой опухоли.
3. Применение производных рапамицина для приготовления фармацевтической композиции, предназначенной для ингибирования или профилактики нарушенной регуляции ангиогенеза или для лечения заболеваний, связанных с нарушенной регуляцией ангиогенеза.
4. Применение по любому из предшествующих пунктов, согласно которому фармацевтическая композиция предназначена для лечения опухолей головного мозга, центральной нервной системы, ободочной кишки, прямой кишки или репродуктивной системы.
5. Применение по любому из пп.1-3, согласно которому фармацевтическую композицию вводят пациенту периодически.
6. Применение производных рапамицина формулы I
Figure 00000001
где R1 обозначает СН3 или С3-С6алкинил,
R2 обозначает Н или -CH2-CH2-OH, и
Х обозначает =О, (Н, Н) или (Н, ОН)
при условии, что R2 не обозначает Н, если Х обозначает =O и R1 обозначает СН3, для приготовления фармацевтической композиции, предназначенной для лечения плотных опухолей, согласно которому фармацевтическую композицию вводят пациенту периодически.
7. Применение по любому из пп.1-3 и 6, согласно которому фармацевтическую композицию применяют в сочетании с лучевой терапией.
8. Применение по любому из пп.1-3 и 6, где производное рапамицина представляет собой 40-0-(2-гидроксиэтил)рапамицин.
9. Применение по п.7, где производное рапамицина представляет собой 40-[3-гидрокси-2-(гидроксиметил)-2-метилпропаноат]-рапамицин или АВТ578.
10. Фармацевтическая комбинация, включающая а) первый агент, представляющий собой производное рапамицина формулы I по п.1, и б) коагент, представляющий собой химиотерапевтический агент, выбранный из
II. антиандрогена или агониста гонадорелина,
III. ингибитора топоизомеразы I и
IV. алкилирующего агента или содержащего платину соединения.
11. Фармацевтическая комбинация, включающая а) первый агент, представляющий собой производное рапамицина формулы I по п.1, и б) коагент, представляющий собой химиотерапевтический агент, выбранный из
III. ингибитора топоизомеразы II, выбранного из антрациклина, митоксантрона и изоксантрона,
IV. агента, обладающего активностью в отношении микротрубочек или антинеопластического антиметаболита,
V. соединения, обладающего способностью воздействовать на/понижать активность протеин- или липидкиназы, или протеин- или липидфосфатазы, другое антиангиогенного соединения или соединения, индуцирующего процессы дифференцировки клеток,
VI. антагониста рецептора брадикинина 1 или ангиотензина II,
VII. ингибитора циклооксигеназы, бисфосфоната, ингибитора гистон-деацетилазы, ингибитора гепараназы, модификатора биологической реакции, ингибитора убиквитина, или ингибитора, блокирующий антиапоптозные пути,
VIII. ингибитора онкогенных изоформ Ras,
IX. ингибитора теломеразы, и
X. ингибитора протеазы, ингибитора матриксной металлопротеазы, ингибитора метионинаминопептидазы или ингибитора протеосомы.
12. Фармацевтическая комбинация по п.11, включающая а) первый агент, представляющий собой производное рапамицина, выбранное из соединений формулы I по п.1, представляющих собой 40-[3-гидрокси-2-(гидроксиметил)-2-метилпропаноат]-рапамицин или АВТ578, и б) коагент, представляющий собой химиотерапевтический агент, выбранный из паклитаксела, гемцитабина, цисплатина, доксорубицина, 5-флуорацила, антиметаболита, модификатора биологической реакции, эпотилона или его производного.
13. Фармацевтическая комбинация по п.11, в которой б) коагент представляет собой таксан, ингибитор VEGF рецептора тирозинкиназы, ингибитор EGF, ErbB2, ЕrbВ3 или ЕrВ4 рецепторов тирозинкиназы, ингибитор PDGF рецептора, соединение, обладающее способностью воздействовать, понижать или ингибировать активность представителей семейства с-Abl, представителей семейства протеинкиназы С, представителей семейства киназ Raf, MEK, SRC, JAK, FAK, PDK или PI(3).
14. Фармацевтическая комбинация по п.11 или 13, где первый агент а) представляет собой 40-0-(2-гидроксиэтил)рапамицин, 40-[3-гидрокси-2-(гидроксиметил)-2-метилпропаноат]-рапамицин или АВТ578.
15. Фармацевтическая комбинация, включающая а) первый агент, представляющий собой рапамицин, и б) коагент, претставляющий собой химиотерапевтический агент, выбранный из ингибитора VEGF рецептора тирозинкиназы, ингибитора EGF, ErbB2, ЕrbВ3 или ЕrВ4 рецепторов тирозинкиназы и ингибитора PDGF рецептора.
16. Фармацевтическая комбинация по пп.11, 13 или 15, где б) коагент представляет собой RhuMab, трастузумаб, Ирессу, OSI-774 или иматиниб.
17. Фармацевтическая комбинация по любому из пп.10-13 и 15, в которой первый агент а) и коагент б) вводят пациенту одновременно или последовательно.
18. Фармацевтическая комбинация по любому из пп.10-13 и 15, в которой первый агент а) вводят пациенту периодически.
19. Фармацевтическая комбинация по любому из пп.10-13 и 15, которую применяют в сочетании с лучевой терапией.
20. Фармацевтическая комбинация, включающая а) первый агент, представляющий собой производное рапамицина, и б) коагент, выбранный из бусульфана, цитарабина, 6-тиогуанина, флударабина гидроксимочевины, прокарбазина, блеомицина, метотрексата, ингибитора топоизомеразы II или соединения, которое направленно действует, понижает или ингибирует активность PDGFR или представителей семейства с-Abl, предназначенная для приготовления лекарственного средства для лечения опухолей кровеносной или лимфатической системы.
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