RU2018142394A - Композиции и способы для лечения нейтропении - Google Patents
Композиции и способы для лечения нейтропении Download PDFInfo
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- RU2018142394A RU2018142394A RU2018142394A RU2018142394A RU2018142394A RU 2018142394 A RU2018142394 A RU 2018142394A RU 2018142394 A RU2018142394 A RU 2018142394A RU 2018142394 A RU2018142394 A RU 2018142394A RU 2018142394 A RU2018142394 A RU 2018142394A
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- plinabulin
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- 239000000203 mixture Substances 0.000 title claims 29
- 238000000034 method Methods 0.000 title claims 27
- 208000004235 neutropenia Diseases 0.000 title claims 10
- 230000000973 chemotherapeutic effect Effects 0.000 claims 28
- UNRCMCRRFYFGFX-TYPNBTCFSA-N plinabulin Chemical compound N1C=NC(\C=C/2C(NC(=C\C=3C=CC=CC=3)/C(=O)N\2)=O)=C1C(C)(C)C UNRCMCRRFYFGFX-TYPNBTCFSA-N 0.000 claims 11
- 229950011498 plinabulin Drugs 0.000 claims 11
- 239000002246 antineoplastic agent Substances 0.000 claims 4
- 229940127089 cytotoxic agent Drugs 0.000 claims 4
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims 3
- 229960003668 docetaxel Drugs 0.000 claims 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 2
- 229940123237 Taxane Drugs 0.000 claims 2
- 229960004316 cisplatin Drugs 0.000 claims 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims 2
- 229960004397 cyclophosphamide Drugs 0.000 claims 2
- -1 ifosamide Chemical compound 0.000 claims 2
- 238000001959 radiotherapy Methods 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 229960000303 topotecan Drugs 0.000 claims 2
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims 2
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims 1
- 229930012538 Paclitaxel Natural products 0.000 claims 1
- KLNFSAOEKUDMFA-UHFFFAOYSA-N azanide;2-hydroxyacetic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OCC(O)=O KLNFSAOEKUDMFA-UHFFFAOYSA-N 0.000 claims 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims 1
- 229960001573 cabazitaxel Drugs 0.000 claims 1
- BMQGVNUXMIRLCK-OAGWZNDDSA-N cabazitaxel Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3C[C@@H]([C@]2(C(=O)[C@H](OC)C2=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=3C=CC=CC=3)C[C@]1(O)C2(C)C)C)OC)C(=O)C1=CC=CC=C1 BMQGVNUXMIRLCK-OAGWZNDDSA-N 0.000 claims 1
- 229960004562 carboplatin Drugs 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 229960000975 daunorubicin Drugs 0.000 claims 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims 1
- 229960004679 doxorubicin Drugs 0.000 claims 1
- 229960001904 epirubicin Drugs 0.000 claims 1
- 229950007221 nedaplatin Drugs 0.000 claims 1
- 229960001756 oxaliplatin Drugs 0.000 claims 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims 1
- 229960001592 paclitaxel Drugs 0.000 claims 1
- 229950005566 picoplatin Drugs 0.000 claims 1
- IIMIOEBMYPRQGU-UHFFFAOYSA-L picoplatin Chemical compound N.[Cl-].[Cl-].[Pt+2].CC1=CC=CC=N1 IIMIOEBMYPRQGU-UHFFFAOYSA-L 0.000 claims 1
- 229960005399 satraplatin Drugs 0.000 claims 1
- 190014017285 satraplatin Chemical compound 0.000 claims 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 1
- 229950002860 triplatin tetranitrate Drugs 0.000 claims 1
- 190014017283 triplatin tetranitrate Chemical compound 0.000 claims 1
- 229960000653 valrubicin Drugs 0.000 claims 1
- ZOCKGBMQLCSHFP-KQRAQHLDSA-N valrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)CCCC)[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1 ZOCKGBMQLCSHFP-KQRAQHLDSA-N 0.000 claims 1
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- A61P35/00—Antineoplastic agents
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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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- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
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- 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
- A61K31/437—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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
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- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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Claims (32)
1. Способ уменьшения нейтропении у субъекта, включающий введение плинабулина или его фармацевтически приемлемой соли субъекту, который в этом нуждается, при этом указанная нейтропения вызвана введением первой химиотерапевтической композиции, содержащей один или более химиотерапевтических агентов, где указанная химиотерапевтическая композиция не содержит доцетаксела, или указанная нейтропения вызвана лучевой терапией.
2. Способ по п. 1, отличающийся тем, что указанная первая химиотерапевтическая композиция не содержит таксан.
3. Способ по п. 1 или 2, включающий введение одной или более дополнительных химиотерапевтических композиций указанному субъекту.
4. Способ по любому из пп. 1-3, отличающийся тем, что указанная первая химиотерапевтическая композиция содержит один химиотерапевтический агент.
5. Способ по любому из пп. 1-3, отличающийся тем, что указанная первая химиотерапевтическая композиция содержит два или более химиотерапевтических агентов.
6. Способ по любому из пп. 1-4, отличающийся тем, что указанная первая химиотерапевтическая композиция содержит один или более агентов, выбранных из группы, состоящей из циклофосфамида, ифозамида, цисплатина, карбоплатина, оксалиплатина, недаплатина, триплатин тетранитрата, фенантриплатина, пикоплатина, сатраплатина, топотекана, иринотекана, доксорубицина, эпирубицина, даунорубицина, валрубицина и их фармацевтически приемлемых солей.
7. Способ по любому из пп. 3-6, отличающийся тем, что по меньшей мере одна из указанных одной или более дополнительных химиотерапевтических композиций содержит доцетаксел.
8. Способ по любому из пп. 3-7, отличающийся тем, что по меньшей мере одна из указанных одной или более дополнительных химиотерапевтических композиций содержит один или более таксанов, выбранных из группы, состоящей из доцетаксела, паклитаксела и кабазитаксела.
9. Способ по любому из пп. 1-8, отличающийся тем, что указанная первая химиотерапевтическая композиция содержит циклофосфамид.
10. Способ по любому из пп. 1-9, отличающийся тем, что указанная первая химиотерапевтическая композиция содержит цисплатин.
11. Способ по любому из пп. 1-10, отличающийся тем, что указанная первая химиотерапевтическая композиция содержит доксорубицин.
12. Способ по любому из пп. 1-11, отличающийся тем, что указанная первая химиотерапевтическая композиция содержит топотекан.
13. Способ по любому из пп. 1-12, включающий введение плинабулина перед введением указанной первой химиотерапевтической композиции.
14. Способ по п. 13, отличающийся тем, что плинабулин вводят в пределах примерно от 1 минуты до 24 часов перед введением указанной первой химиотерапевтической композиции.
15. Способ по любому из пп. 1-12, включающий введение плинабулина после введения указанной первой химиотерапевтической композиции.
16. Способ по п. 15, отличающийся тем, что плинабулин вводят в пределах примерно от 1 минуты до 24 часов после введения указанной первой химиотерапевтической композиции.
17. Способ по любому из пп. 1-12, отличающийся тем, что плинабулин и указанную первую химиотерапевтическую композицию вводят по существу одновременно.
18. Способ по любому из пп. 3, 7 или 8, включающий:
введение плинабулина перед введением указанной первой химиотерапевтической композиции; и
введение указанных дополнительных одной или более химиотерапевтических композиций после введения указанной первой химиотерапевтической композиции.
19. Способ по любому из пп. 3, 7 или 8, включающий:
введение указанной первой химиотерапевтической композиции перед введением плинабулина; и
введение указанных дополнительных одной или более химиотерапевтических композиций после введения плинабулина.
20. Способ по любому из пп. 3, 7 или 8, включающий:
введение указанной первой химиотерапевтической композиции перед введением указанных дополнительных одной или более химиотерапевтических композиций; и
введение плинабулина после введения указанных дополнительных одного или более химиотерапевтических агентов.
21. Способ по любому из пп. 18-20, отличающийся тем, что период времени между введением каждого из плинабулина, указанной первой химиотерапевтической композиции и указанных дополнительных одной или более химиотерапевтических композиций независимо выбран из диапазона примерно от 1 минуты до 24 часов.
22. Способ по любому из пп. 1-21, включающий проведение лучевой терапии указанному субъекту.
23. Способ по любому из пп. 1-22, включающий идентификацию указанного субъекта как страдающего нейтропенией.
24. Способ по любому из пп. 1-23, отличающийся тем, что указанная нейтропения, вызванная первой химиотерапевтической композицией, представляет собой нейтропению 3 или 4 степени.
25. Способ по любому из пп. 1-24, включающий идентификацию указанного субъекта как имеющего риск развития нейтропении.
26. Способ по любому из пп. 1-25, отличающийся тем, что указанное уменьшение нейтропении включает уменьшение вероятности возникновения или уменьшение тяжести нейтропении у указанного субъекта.
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| PCT/US2017/035991 WO2017214052A1 (en) | 2016-06-06 | 2017-06-05 | Composition and method for reducing neutropenia |
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