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1. (WO2005063297) POLYTHERAPIE A BASE DE MELATONINE DESTINEE A AMELIORER LA QUALITE DU SOMMEIL
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique
We claim:
1. A pharmaceutical composition comprising a melatonin agent and a sedative agent, wherein said sedative agent modulates the activity of a GABA receptor and has K, less than about 300 nM in a GABA-receptor binding assay.
2. The pharmaceutical composition of claim 1, wherein said Kj is less than about 150 nM.
3. The pharmaceutical composition of claim 1, wherein said K is less than about 75 nM.
4. The pharmaceutical compositon of claim 1, wherein said K is less than about 30 nM.
5. The pharmaceutical composition of claim 1, wherein said melatonin agent is melatonin, TAK-375, agomelatine, LY 156735, CGP 52608, low-dose melatonin A, GR196429, S20242, S23478, S24268, S25150, BMS-214778, melatonin receptor research compound A, GW290569, controlled release melatonin, luzindole, GRl 35531, melatonin agonist A, melatonin analogue B, melatonin agonist C, melatomn agonist D, melatonin agonist E, melatonin agonist F, melatonin agonist G, melatonin agonist H, melatonin agonist I, melatonin analog J , melatonin analog K, melatonin analog L, AH-001, GG-012, enol-3-IPA, ML-23, SL-18.1616, IP-100-9, melatonin low-dose B, sleep inducing peptide A, oros-melatonin, AH-017, AH-002, IP-101, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
6. The pharmaceutical composition of claim 1, wherein said melatonin agent is melatonin, TAK-375, agomelatine, ML-23, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
7. The pharmaceutical composition of claim 1, wherein said melatonin agent is melatonin, or a phannaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
8. The pharmaceutical composition of claim 1, wherein said sedative agent is racemic zopiclone, eszopiclone, indiplon, zolpidem, zaleplon, gaboxadol, baclofen, bicuuculline, CACA, β-CCP, CGP 35348, CGP 46381, CGP 52432, CGP 54626, CGP 55845, clonazepam, diazepam, flumazenil, gabapentin, 2-hydroxysaclofen, isoguvacine, lamotrigine, lorazepam, L-655708, midazolam, muscimol, phaclofen, phenytoin, pregabalin, progabide, riluzole, saclofen, SCH 50911, SKF 97541, SR 95531, tiagabine, TPMPA, topiramate, valproic acid, vigabatrin, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
9. The pharmaceutical composition of claim 1, wherein said sedative agent is racemic zopiclone, eszopiclone, indiplon, zolpidem, zaleplon, gaboxadol, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof
10. The pharmaceutical composition of claim 1, wherein said sedative agent is racemic zopiclone, eszopiclone, indiplon, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
11. The pharmaceutical composition of claim 1, wherein said sedative agent is eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
12. The phannaceutical composition of claim 1, wherein said melatonin agent is melatonin, TAK-375, agomelatine, LY 156735, CGP 52608, low-dose melatonin A, GR196429, S20242, S23478, S24268, S25150, BMS-214778, melatonin receptor research compound A, GW290569, controlled release melatonin, luzindole, GR135531, melatonin agonist A, melatonin analogue B, melatonin agonist C, melatonin agonist D, melatonin agonist E, melatonin agonist F, melatonin agonist G, melatonin agonist H, melatonin agonist I, melatonin analog J , melatonin analog K, melatonin analog L, AH-001, GG-012, enol-3-IPA, ML-23, SL-18.1616, IP-100-9, melatonin low-dose B, sleep inducing peptide A, oros-melatonin, AH-017, AH-002, IP-101, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof; and said sedative agent is racemic zopiclone, eszopiclone, indiplon, zolpidem, zaleplon, gaboxadol, baclofen, bicuuculline, CACA, β-CCP, CGP 35348, CGP 46381, CGP 52432, CGP 54626, CGP 55845, clonazepam, diazepam, flumazenil, gabapentin, 2-hydroxysaclofen, isoguvacine, lamotrigine, lorazepam, L-655708, midazolam, muscimol, phaclofen, phenytoin, pregabalin, progabide, riluzole, saclofen, SCH 50911, SKF 97541, SR 95531, tiagabine, TPMPA, topiramate, valproic acid, vigabatrin, or a phannaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
13. A pharmaceutical composition comprising a sedative agent and a melatonin agent, wherein said sedative agent is eszopiclone, or a phannaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof, and said melatonin agent is melatonin, TAK-375, agomelatine, ML-23, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.

14. A pharmaceutical composition comprising a sedative agent and a melatonin agent, wherein said sedative agent is eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof, and said melatomn agent is melatonin, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
15. A phannaceutical composition consisting essentially of a melatonin agent, a sedative agent, and at least one phannaceutically acceptable carrier; wherein said sedative agent modulates the activity of a GABA receptor and has K; less than about 300 nM in a GABA-receptor binding assay.
16. The pharmaceutical composition of claim 15, wherein said Kj is less than about 150 nM.
17. The phannaceutical composition of claim 15, wherein said Kj is less than about 75 nM.
18. The phannaceutical compositon of claim 15, wherein said Kj is less than about 30 nM.
19. The phannaceutical composition of claim 15, wherein said melatonin agent is melatonin, TAK-375, agomelatine, LY 156735, CGP 52608, low-dose melatonin A, GR196429, S20242, S23478, S24268, S25150, BMS-214778, melatonin receptor research compound A, GW290569, controlled release melatonin, luzindole, GR135531, melatonin agonist A, melatonin analogue B, melatonin agonist C, melatonin agonist D, melatonin agonist E, melatonin agonist F, melatonin agonist G, melatonin agonist H, melatonin agonist I, melatonin analog J , melatonin analog K, melatonin analog L, AH-001, GG-012, enol-3-IPA, ML-23, SL-18.1616, IP-100-9, melatonin low-dose B, sleep inducing peptide A, oros-melatonin, AH-017, AH-002, IP-101, or a phannaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
20. The pharmaceutical composition of claim 15, wherein said melatonin agent is melatonin, TAK-375, agomelatine, ML-23, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
21. The pharmaceutical composition of claim 15, wherein said melatonin agent is melatonin, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
22. The pharmaceutical composition of claim 15, wherein said sedative agent is racemic zopiclone, eszopiclone, indiplon, zolpidem, zaleplon, gaboxadol, baclofen, bicuuculline, CACA, β-CCP, CGP 35348, CGP 46381, CGP 52432, CGP 54626, CGP 55845, clonazepam, diazepam, flumazenil, gabapentin, 2-hydroxysaclofen, isoguvacine, lamotrigine, lorazepam, L-655708, midazolam, muscimol, phaclofen, phenytoin, pregabalin, progabide, riluzole, saclofen, SCH 50911, SKF 97541, SR 95531, tiagabine, TPMPA, topiramate, valproic acid, vigabatrin, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
23. The pharmaceutical composition of claim 15, wherein said sedative agent is racemic zopiclone, eszopiclone, indiplon, zolpidem, zaleplon, gaboxadol, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof
24. The phannaceutical composition of claim 15, wherein said sedative agent is racemic zopiclone, eszopiclone, indiplon, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
25. The pharmaceutical composition of claim 15, wherein said sedative agent is eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
26. The phannaceutical composition of claim 15, wherein said melatonin agent is melatonin, TAK-375, agomelatine, LY 156735, CGP 52608, low-dose melatonin A, GR196429, S20242, S23478, S24268, S25150, BMS-214778, melatonin receptor research compound A, GW290569, controlled release melatonin, luzindole, GR135531, melatonin agonist A, melatonin analogue B, melatomn agonist C, melatonin agonist D, melatonin agonist E, melatonin agonist F, melatonin agonist G, melatonin agonist H, melatonin agonist I, melatonin analog J , melatonin analog K, melatonin analog L, AH-001, GG-012, enol-3-DPA, ML-23, SL-18.1616, IP-100-9, melatonin low-dose B, sleep inducing peptide A, oros-melatonin, AH-017, AH-002, IP-101, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof; and said sedative agent is racemic zopiclone, eszopiclone, indiplon, zolpidem, zaleplon, gaboxadol, baclofen, bicuuculline, CACA, β-CCP, CGP 35348, CGP 46381, CGP 52432, CGP 54626, CGP 55845, clonazepam, diazepam, flumazenil, gabapentin, 2-hydroxysaclofen, isoguvacine, lamotrigine, lorazepam, L-655708, midazolam, muscimol, phaclofen, phenytoin, pregabalin, progabide, riluzole, saclofen, SCH 50911, SKF 97541, SR 95531, tiagabine, TPMPA, topiramate, valproic acid, vigabatrin, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
27. A pharmaceutical composition consisting essentially of a sedative agent, a melatonin agent, and at least one phannaceutically acceptable carrier; wherein said sedative agent is eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof, and said melatomn agent is melatomn, TAK-375, agomelatine, ML-23, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.

28. A pharmaceutical composition consisting essentially of a sedative agent, a melatonin agent, and at least one phannaceutically acceptable canier; wherein said sedative agent is eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof, and said melatonin agent is melatonin, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
29. Products for containing a therapeutically effective amount of a melatonin agent and a therapeutically effective amount of a sedative agent, wherein said sedative agent modulates the activity of a GABA receptor and has a Kj less than about 300 nM in a GABA-receptor binding assay; as a combined preparation for simultaneous, separate, or sequential use in the treatment of a sleep abnormality.
30. The product of claim 29, wherein said Kj is less than about 150 nM.
31. The product of claim 29, wherein said K is less than about 75 nM.
32. The product of claim 29, wherein said K, is less than about 30 nM.
33. The product of claim 29, wherein said melatonin agent is melatonin, TAK-375, agomelatine, LY 156735, CGP 52608, low-dose melatonin A, GR196429, S20242, S23478, S24268, S25150, BMS-214778, melatonin receptor research compound A, GW290569, controlled release melatonin, luzindole, GRl 35531, melatonin agonist A, melatonin analogue B, melatonin agonist C, melatonin agonist D, melatonin agomst E, melatonin agonist F, melatonin agonist G, melatonin agonist H, melatonin agonist I, melatonin analog J , melatonin analog K, melatonin analog L, AH-001, GG-012, enol-3-IPA, ML-23, SL-18.1616, IP-100-9, melatonin low-dose B, sleep inducing peptide A, oros-melatonin, AH-017, AH-002, IP-101, or a phannaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
34. The product of claim 29, wherein said melatonin agent is melatomn, TAK-375, agomelatine, ML-23, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
35. The product of claim 29, wherein said melatonin agent is melatonin, or a phannaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
36. The product of claim 29, wherein said sedative agent is racemic zopiclone, eszopiclone, indiplon, zolpidem, zaleplon, gaboxadol, baclofen, bicuuculline, CACA, β- CCP, CGP 35348, CGP 46381, CGP 52432, CGP 54626, CGP 55845, clonazepam, diazepam, flumazenil, gabapentin, 2-hydroxysaclofen, isoguvacine, lamotrigine, lorazepam, L-655708, midazolam, muscimol, phaclofen, phenytoin, pregabalin, progabide, riluzole, saclofen, SCH 50911, SKF 97541, SR 95531, tiagabine, TPMPA, topiramate, valproic acid, vigabatrin, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
37. The product of claim 29, wherein said sedative agent is racemic zopiclone, eszopiclone, indiplon, zolpidem, zaleplon, gaboxadol, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof
38. The product of claim 29, wherein said sedative agent is racemic zopiclone, eszopiclone, indiplon, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
39. The product of claim 29, wherein said sedative agent is eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
40. The product of claim 29, wherein said melatonin agent is melatonin, TAK-375, agomelatine, LY 156735, CGP 52608, low-dose melatonin A, GR196429, S20242, S23478, S24268, S25150, BMS-214778, melatonin receptor research compound A, GW290569, controlled release melatonin, luzindole, GRl 35531, melatonin agonist A, melatonin analogue B, melatonin agonist C, melatonin agonist D, melatonin agonist E, melatonin agonist F, melatonin agonist G, melatonin agonist H, melatonin agonist I, melatonin analog J , melatonin analog K, melatonin analog L, AH-001, GG-012, enol-3-IPA, ML-23, SL-18.1616, IP-100-9, melatonin low-dose B, sleep inducing peptide A, oros-melatonin, AH-017, AH-002, IP-101, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof; and said sedative agent is racemic zopiclone, eszopiclone, indiplon, zolpidem, zaleplon, gaboxadol, baclofen, bicuuculline, CACA, β-CCP, CGP 35348, CGP 46381, CGP 52432, CGP 54626, CGP 55845, clonazepam, diazepam, flumazenil, gabapentin, 2-hydroxysaclofen, isoguvacine, lamotrigine, lorazepam, L-655708, midazolam, muscimol, phaclofen, phenytoin, pregabalin, progabide, riluzole, saclofen, SCH 50911, SKF 97541, SR 95531, tiagabine, TPMPA, topiramate, valproic acid, vigabatrin, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.

41. Products for containing a therapeutically effective amount of a melatomn agent and a therapeutically effective amount of a sedative agent; wherein said sedative agent is eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co- crystal thereof, and said melatonin agent is melatonin, TAK-375, agomelatine, ML-23, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof; as a combined preparation for simultaneous, separate, or sequential use in the treatment of a sleep abnormality.
42. Products for containing a therapeutically effective amount of a melatonin agent and a therapeutically effective amount of a sedative agent; wherein said sedative agent is eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof, and said melatonin agent is melatonin, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof; as a combined preparation for simultaneous, separate, or sequential use in the treatment of a sleep abnormality.
43. The product of any one of claims 29-42, wherein said sleep abnonnality is difficulty falling asleep, difficulty staying asleep, or waking up too early.
44. Products for containing a therapeutically effective amount of a melatonin agent and a therapeutically effective amount of a sedative agent, wherein said sedative agent modulates the activity of a GABA receptor and has a Kj less than about 300 nM in a GABA-receptor binding assay; as a combined preparation for simultaneous, separate, or sequential use in the treatment of insomnia.
45. The product of claim 44, wherein said K; is less than about 150 nM.
46. The product of claim 44, wherein said K, is less than about 75 nM.
47. The product of claim 44, wherein said K; is less than about 30 nM.
48. The product of claim 44, wherein said melatonin agent is melatonin, TAK-375, agomelatine, LY 156735, CGP 52608, low-dose melatonin A, GR196429, S20242, S23478, S24268, S25150, BMS-214778, melatonin receptor research compound A, GW290569, controlled release melatonin, luzindole, GRl 35531, melatonin agonist A, melatonin analogue B, melatonin agonist C, melatonin agonist D, melatonin agonist E, melatomn agonist F, melatonin agonist G, melatonin agonist H, melatonin agonist I, melatonin analog J , melatonin analog K, melatonin analog L, AH-001, GG-012, enol-3-IPA, ML-23, SL-18.1616, IP-100-9, melatonin low-dose B, sleep inducing peptide A, oros-melatonin, AH-017, AH-002, IP-101, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
49. The product of claim 44, wherein said melatonin agent is melatomn, TAK-375, agomelatine, ML-23, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.

50. The product of claim 44, wherein said melatonin agent is melatonin, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
51. The product of claim 44, wherein said sedative agent is racemic zopiclone, eszopiclone, indiplon, zolpidem, zaleplon, gaboxadol, baclofen, bicuuculline, CACA, β-CCP, CGP 35348, CGP 46381, CGP 52432, CGP 54626, CGP 55845, clonazepam, diazepam, flumazenil, gabapentin, 2-hydroxysaclofen, isoguvacine, lamotrigine, lorazepam, L-655708, midazolam, muscimol, phaclofen, phenytoin, pregabalin, progabide, riluzole, saclofen, SCH 50911, SKF 97541, SR 95531, tiagabine, TPMPA, topiramate, valproic acid, vigabatrin, or a phannaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
52. The method of claim 44, wherein said sedative agent is racemic zopiclone, eszopiclone, indiplon, zolpidem, zaleplon, gaboxadol, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof
53. The product of claim 44, wherein said sedative agent is racemic zopiclone, eszopiclone, indiplon, or a phannaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
54. The product of claim 44, wherein said sedative agent is eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof.
55. The product of claim 44, wherein said melatonin agent is melatonin, TAK-375, agomelatine, LY 156735, CGP 52608, low-dose melatonin A, GR196429, S20242, S23478,

S24268, S25150, BMS-214778, melatonin receptor research compound A, GW290569, controlled release melatomn, luzindole, GR135531, melatonin agonist A, melatonin analogue B, melatomn agonist C, melatonin agonist D, melatonin agonist E, melatonin agonist F, melatonin agonist G, melatonin agonist H, melatonin agonist I, melatonin analog J , melatonin analog K, melatonin analog L, AH-001, GG-012, enol-3-IPA, ML-23, SL-18.1616, IP- 100-9, melatonin low-dose B, sleep inducing peptide A, oros-melatonin, AH-017, AH-002, IP-101, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof; and said sedative agent is racemic zopiclone, eszopiclone, indiplon, zolpidem, zaleplon, gaboxadol, baclofen, bicuuculline, CACA, β-CCP, CGP 35348, CGP 46381, CGP 52432, CGP 54626, CGP 55845, clonazepam, diazepam, flumazenil, gabapentin, 2-hydroxysaclofen, isoguvacine, lamotrigine, lorazepam, L-655708, midazolam, muscimol, phaclofen, phenytoin, pregabalin, progabide, riluzole, saclofen, SCH 50911, SKF 97541, SR 95531, tiagabine, TPMPA, topiramate, valproic acid, vigabatrin, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof. 56. Products for containing a therapeutically effective amount of a melatonin agent and a therapeutically effective amount of a sedative agent; wherein said sedative agent is eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof, and said melatomn agent is melatonin, TAK-375, agomelatine, ML-23, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof; as a combined preparation for simultaneous, separate, or sequential use in the treatment of insomnia.
57. Products for containing a therapeutically effective amount of a melatonin agent and a therapeutically effective amount of a sedative agent; wherein said sedative agent is eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof, and said melatonin agent is melatonin, or a pharmaceutically acceptable salt, solvate, clathrate, polymoφh, or co-crystal thereof; as a combined preparation for simultaneous, separate, or sequential use in the treatment of insomnia.
58. The product of any one of claims 44-57, wherein said insomnia is transient insomnia.
59. The product of any one of claims 44-57, wherein said insomnia is short-term insomnia.
60. The product of any one of claims 44-57, wherein said insomnia is chronic insomnia.