Compositions including opioids and methods of their use in treating pain 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2005107467 A2 2005-11-17 [WO2005107467]WO2005107467 A3 2006-04-13 [WO2005107467] / 2005-11-172006-04-13
申请号/申请日
2005WO-US15044 / 2005-04-29
发明人
LEIGHTON HARRY JEFFERSON;BORSOOK DAVID;LAWTON STEPHEN ASHLEY;
申请人
DESCARTES THERAPEUTICS;
主分类号
IPC分类号
A01N-043/42
摘要
(WO2005107467) The invention features compositions for treatment of pain or nociception and methods of their use.  The compositions include the combination of two or more drugs, such as an opioid (e.g., delta, kappa, or mu), a non-steroidal anti-inflammatory drug (NSAID) or acetaminophen, and a dopaminergic agent.  These drug combinations may be administered alone (i.e., treatment is accomplished using a composition that consists of or consists essentially of the drug combination itself), or the drug combinations may be administered in conjunction with yet additional compounds.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2004US-60567539 2004-05-03 2004US-60584534 2004-07-01
主权利要求
(WO2005107467) CLAIMS 1. A method of treating pain or nociception, said method comprising administering to a subject in need thereof a combination of (i) an opioid (ii) a non- steroidal anti-inflammatory drug (NSAID) or acetaminophen, and (iii) a dopaminergic agent, wherein said combination is administered in a therapeutically effective amount. 2. The method of claim 1, wherein said opioid is alfentanil, allylprodine, alphaprodine, anileridine, benzylmoφhine, bezitramide, buprenoφhine, butoφhanol, clonitazene, codeine, cyclazocine, desomoφhine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromoφhine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmoφhine, etonitazene, fentanyl, heroin, hydrocodone, hydromoφhone, hydroxypethidine, isomethadone, ketobemidone, levalloφhan, levoφhanol, levophenacylmoφhan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, moiphine, myrophine, nalbuphine, narceine, nicomoφhine, norlevoφhanol, nonnethadone, naloφhine, normoφhine, noφipanone, opium, oxycodone, oxymoφhone, papaveretum, pentazocine, pethidine, phenadoxone, phenomoφhan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propiram, propoxyphene, sufentanil, tramadol, or tilidine. 3. The method of claim 1, wherein said NSAID is aspirin, diclofenac, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, nabumetone, naproxen, oxaprozin, piroxicam, sulindac, tolmetin, celecoxib, or rofecoxib. 4. The method of claim 1, wherein said dopaminergic agent is a dopamine precursor, monoamine oxidase inhibitor, catechol-O-methyl transferase (COMT) inhibitor, dopamine releaser, dopamine reuptake inhibitor, postsynaptic dopamine receptor agonist, or presynaptic dopamine receptor antagonist. 5. The method of claim 4, wherein said dopamine precursor is levodopa. 6. The method of claim 4, wherein said monoamine oxidase inhibitor is pargyline, deprenyl (R or S), Ro 16-6491, clorgyline, hydralazine, hydroxylamine, ipronazid, 6-methoxy-tetrahydiO-9H-pyrido-indole, nialamide, quinacrine, Ro 41- 1049, semicarbazide, or tranylcypromine. 7. The method of claim 4, wherein said catechol-O-methyl transferase (COMT) inhibitor is tropolone, 3,5-dinitrocatechol, or RO 41-0960. 8. The method of claim 4, wherein said dopamine releaser is amphetamine, amantadine, or apomoφhine. 9. The method of claim 4, wherein said dopamine reuptake inhibitor is amfonelic acid, BTCP, β-CFT, β-CIT, 4',4"-difluoro-3α-(diphenylmethoxy) tropane, 4'-chloro-3α-diρhenylmethoxytoρane, GBR-12683, GBR-12909, GBR- 12935, GBR-12935, GBR-13069, GBR-13098, GYKI 52895, benztropine, amphetamine, mazindol, nomifensine, indatraline, or bupropion. 10. The method of claim 4, wherein said postsynaptic dopamine receptor agonist is A-77636. 11. The method of claim 4, wherein said presynaptic dopamine receptor antagonist (+)-UH232 or (+)-AJ76. 12. The method of claim 1, wherein said dopaminergic agent is a tricyclic antidepressant. 13. The method of claim 12, wherein said tricyclic antidepressant is amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, or himipramine. 14. The method of claim 1, wherein said pain is chronic pain. 15. The method of claim 14, wherein said chronic pain is neuropathic pain. 16. The method of claim 1, wherein said pain is acute pain. 17. The method of claim 1, wherein said opioid is administered in a subtherapeutically effective amount. 18. The method of claim 1, wherein said combination is (i) oxycodone, (ii) acetaminophen, and (iii) bupropion. 19. The method of claim 1, wherein said combination is (i) hydrocodone, (ii) acetaminophen, and (iii) bupropion. 20. The method of claim 1, wherein said combination is (i) tramadol, (ii) acetaminophen, and (iii) bupropion. 21. The method of claim 1, wherein said subject is a human. 22. The method of claim 1, wherein 0.001 to 25 mg/kg per day of said opioid is administered. 23. The method of claim 22, wherein 0.005 to 10 mg/kg per day of said opioid is administered. 24. A method of reducing the side effects of opioid treatment, said method comprising administering to a subject in need thereof a combination of (i) an opioid (ii) a non-steroidal anti-inflammatory drug (NSAID) or acetaminophen, and (iii) a dopaminergic agent, wherein said combination is administered in a therapeutically effective amount to treat pain or nociception, and wherein a side effect associated with said opioid is reduced. , 25. The method of claim 24, wherein said side effect is nausea, emesis, sedation, mental confusion, lightheadedness, hyperalgesia, urinary retention, respiratory depression, pruritus, miosis, hallucinations, constipation, myoclonic seizures, euphoria, excitation, dysphoria, hypotension, tolerance, or dependence. 26. The method of claim 24, wherein said combination is (i) oxycodone, (ii) acetaminophen, and (iii) bupropion. 27. The method of claim 24, wherein said combination is (i) hydrocodone, (ii) acetaminophen, and (iii) bupropion. 28. The method of claim 24, wherein said combination is (i) tramadol, (ii) acetaminophen, and (iii) bupropion. 29. The method of claim 24, wherein said subject is a human. 30. The method of claim 24, wherein 0.001 to 25 mg/kg per day of said opioid is administered. 31. The method of claim 30, wherein 0.005 to 10 mg/kg per day of said opioid is administered. 32. A phannaceutical composition comprising (i) an opioid, (ii) a non- steroidal anti-inflammatory drag (NSAID) or acetaminophen, and (iii) a dopaminergic agent. 33. The phannaceutical composition of claim 32, further comprising a pharmaceutically acceptable carrier. 34. The pharmaceutical composition of claim 32, wherein said opioid is present in a subtherapeutically effective amount. 35. The pharmaceutical composition of claim 32, wherein said combination comprises (i) oxycodone, (ii) acetaminophen, and (iii) bupropion. 36. The pharmaceutical composition of claim 32, wherein said combination comprises (i) hydrocodone, (ii) acetaminophen, and (iii) bupropion. 37. The pharmaceutical composition of claim 32, wherein said combination comprises (i) tramadol, (ii) acetaminophen, and (iii) bupropion. 38. A kit comprising (a) combination of (i) an opioid, (ii) a non-steroidal anti-inflammatory drug (NSAID) or acetaminophen, and (iii) a dopaminergic agent, and (b) instructions for administering said combination to treat pain or nociception. 39. The kit of claim 38, wherein said opioid is present in a subtherapeutically effective amount. 40. The kit of claim 38, wherein said combination comprises (i) oxycodone, (ii) acetaminophen, and (iii) bupropion. 41. The kit of claim 38, wherein said combination comprises (i) hydrocodone, (ii) acetaminophen, and (iii) bupropion. 42. The kit of claim 38, wherein said combination comprises (i) tramadol, (ii) acetaminophen, and (iii) bupropion. 43. The kit of claim 38, wherein said instructions comprise administering 0.001 to 25 mg/kg per day of said opioid. 44. The kit of claim 40, wherein said instructions comprise administering 0.005 to 10 mg/kg per day of said opioid. 45. A method of treating pain or nociception, said method comprising administering to a subject in need thereof a combination of (i) a delta or kappa opioid and (ii) a dopaminergic agent, wherein said combination is administered in a therapeutically effective amount. 46. The method of claim 45, wherein said delta opioid is deltoφhin I and II, DALDA, DPDPE/DADLE, [D-Ala2, D-Leu5]-enkephalin, SNC80, SNC162, SNC121, DSLET, BW373U86, FIT, or SB205607. 47. The method of claim 45, wherein said kappa opioid is bremazocine, [Arg6]-dynoφhin A (1-13), GR 89696, ICI-204,448, naloxone benzoylhydrazone, U-50488 methane sulfonate, (-)-trans-(lS,2S)-U-50488, (+)-trans-(lR,2R)-U- 50488, U-62066, or U-69593. 48. The method of claim 45, wherein said dopaminergic agent is a dopamine precursor, monoamine oxidase inhibitor, catechol-O-methyl transferase (COMT) inhibitor, dopamine releaser, dopamine reuptake inhibitor, postsynaptic dopamine receptor agonist, or presynaptic dopamine receptor antagonist. 49. The method of claim 48, wherein said dopamine precursor is levodopa. 50. The method of claim 48, wherein said monoamine oxidase inhibitor is pargyline, deprenyl (R or S), Ro 16-6491, clorgyline, hydralazine, hydroxylamine, ipronazid, 6-methoxy-tetrahydro-9H-pyrido-indole, nialamide, quinacrine, Ro 41- 1049, semicarbazide, or tranylcypromine. 51. The method of claim 48, wherein said catechol-O-methyl transferase (COMT) inhibitor is tropolone, 3,5-dinitiOcatechol, or RO 41-0960. 52. The method of claim 48, wherein said dopamine releaser is amphetamine, amantadine, or apomoφhine. 53. The method of claim 48, wherein said dopamine reuptake inhibitor is amfonelic acid, BTCP, β-CFT, β-CIT, 4',4"-difluoro-3α-(diphenylmethoxy) tropane, 4'-chloro-3α-diρhenylmethoxytoρane, GBR-12683, GBR-12909, GBR- 12935, GBR-12935, GBR-13069, GBR-13098, GYKI 52895, benztropine, amphetamine, mazindol, nomifensine, indatraline, or bupropion. 54. The method of claim 48, wherein said postsynaptic dopamine receptor agonist is A-77636. 55. The method of claim 48, wherein said presynaptic dopamine receptor antagonist (+)-UH232 or (+)-AJ76. 56. The method of claim 45, wherein said dopaminergic agent is a tricyclic antidepressant. 57. The method of claim 56, wherein said tricyclic antidepressant is amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, or trimipramine. 58. The method of claim 45, wherein said pain is chronic pain. 59. The method of claim 58, wherein said chronic pain is neuropathic pain. 60. The method of claim 45, wherein said pain is acute pain. 61. The method of claim 45, wherein said delta or kappa opioid is administered in a subtherapeutically effective amount. 62. The method of claim 45, wherein said subject is a human. 63. A method of reducing the side effects of opioid treatment, said method comprising administering to a subject in need thereof a combination of (i) a delta or kappa opioid and (ii) a dopaminergic agent, wherein said combination is administered in a therapeutically effective amount to treat pain or nociception, and wherein a side effect associated with said delta or kappa opioid is reduced. 64. The method of claim 63, wherein said side effect is nausea, emesis, sedation, mental confusion, lightheadedness, hyperalgesia, urinary retention, respiratory depression, pruritus, miosis, hallucinations, constipation, myoclonic seizures, euphoria, excitation, dysphoria, hypotension, tolerance, or dependence. 65. The method of claim 63, wherein said delta opioid is deltoφhin I and II, DALDDAA,, DDPPDDPPEE//DDAADDLLEE,, [[DD--AAllaa22,, DD--LLeeuu55]]--eeιnkephalin, SNC80, SNC162 SNC121, DSLET, BW373U86, FIT, or SB205607. 66. The method of claim 63, wherein said kappa opioid is bremazocine, [Arg6]-dynoφhin A (1-13), GR 89696, ICI-204,448, naloxone benzoylhydrazone, U-50488 methane sulfonate, (-)-trans-(lS,2S)-U-50488, (+)-trans-(lR,2R)-U- 50488, U-62066, or U-69593. 67. The method of claim 63, wherein said dopaminergic agent is bupropion. 68. The method of claim 63 wherein said subject is a human. 69. The method of claim 63, wherein 0.001 to 25 mg/kg per day of said delta or kappa opioid is administered. 70. The method of claim 69, wherein 0.005 to 10 mg/kg per day of said delta or kappa opioid is administered. 71. A pharmaceutical composition comprising (i) a delta or kappa opioid and (ii) a dopaminergic agent. 72. The phannaceutical composition of claim 71, further comprising a phannaceutically acceptable earner. 73. The pharmaceutical composition of claim 71, wherein said opioid is present in a subtherapeutically effective amount. 74. The pharmaceutical composition of claim 71, wherein said delta opioid is deltoφhin l and II, DALDA, DPDPE/DADLE, [D-Ala2, D-Leu5]-enkephalin, SNC80, SNC162, SNC121, DSLET, BW373U86, FIT, or SB205607. 75. The pharmaceutical composition of claim 71, wherein said kappa opioid is bremazocine, [Arg6]-dynoφhin A (1-13), GR 89696, ICI-204,448, naloxone benzoylhydrazone, U-50488 methane sulfonate, (-)-tτans-(lS,2S)-U- 50488, (+)-trans-(lR,2R)-U-50488, U-62066, or U-69593. 76. The pharmaceutical composition of claim 71, wherein said dopaminergic agent is bupropion. 77. A kit comprising (i) combination of a delta or kappa opioid and a dopaminergic agent, and (ii) instructions for administering said combination to treat pain or nociception. 78. The kit of claim 77, wherein said delta opioid is deltoφhin I and II, DALDA, DPDPE/DADLE, [D-Ala2, D-Leu5]-enkephalin, SNC80, SNC162, SNC121, DSLET, BW373U86, FIT, or SB205607. 79. The kit of claim 77, wherein said kappa opioid is bremazocine, [Arg6]- dynoφhin A (1-13), GR 89696, ICI-204,448, naloxone benzoylhydrazone, U- 50488 methane sulfonate, (-)-tτans-(lS,2S)-U-50488, (+)-trans-(lR,2R)-U-50488, U-62066, or U-69593. 80. The kit of claim 77, wherein said dopaminergic agent is bupropion. 81. The kit of claim 77, wherein said instructions comprise administering 0.001 to 25 mg/kg per day of said delta or kappa opioid. 82. The kit of claim 81, wherein said instructions comprise administering 0.005 to 10 mg/kg per day of said delta or kappa opioid. 83. A method of treating pain or nociception, said method comprising administering to a human in need thereof a combination of (i) an opioid and (ii) bupropion, wherein said combination is administered in a therapeutically effective amount. 84. The method of claim 83, wherein said opioid is alfentanil, allylprodine, alphaprodine, anileridine, benzylmoφhine, bezitramide, buprenoφhine, butoiphanol, clonitazene, codeine, cyclazocine, desomoφhine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromoφhine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmoφhine, etonitazene, fentanyl, heroin, hydrocodone, hydromoφhone, hydroxypethidine, isomethadone, ketobemidone, levalloiphan, levoφhanol, levophenacylmoφhan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, moiphine, myrophine, nalbuphine, narceine, nicomoφhine, norlevoφhanol, nonnethadone, naloφhine, nonnoφhine, noipipanone, opium, oxycodone, oxymoφhone, papaveretum, pentazocine, pethidine, phenadoxone, phenomoφhan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propiram, propoxyphene, sufentanil, tramadol, or tilidine. 85. The method of claim 83, wherein said pain is chronic pain. \ 86. The method of claim 85, wherein said chronic pain is neuropathic pain. 87. The method of claim 83, wherein said pain is acute pain. 88. The method of claim 83, wherein said opioid is administered in a subtherapeutically effective amount. 89. The method of claim 83, wherein said opioid is moφhine. 90. The method of claim 88, wherein said combination comprises between about 15:1 and 5:1 bupropion to moiphine. 91. The method of claim 83, wherein 0.001 to 25 mg/kg per day of said opioid is administered. 92. The method of claim 91, wherein 0.005 to 10 mg/kg per day of said opioid is administered. 93. The method of claim 83, wherein said method comprises administering to a human in need thereof a combination consisting essentially of (i) an opioid and (ii) bupropion, wherein said combination is administered in a therapeutically effective amount. 94. A method of reducing the side effects of opioid treatment, said method comprising administering to a subject in need thereof a combination of (i) an opioid and (ii) bupropion, wherein said combination is administered in a therapeutically effective amount to treat pain or nociception, and wherein a side effect associated with said opioid is reduced. 95. The method of claim 94, wherein said side effect is nausea, emesis, sedation, mental confusion, lightheadedness, hyperalgesia, urinary retention, respiratory depression, pruritus, miosis, hallucinations, constipation, myoclonic seizures, euphoria, excitation, dysphoria, hypotension, tolerance, or dependence. 96. The method of claim 94, wherein said opioid is moφhine. 97. The method of claim 96, wherein said combination comprises between about 15: 1 and 5:1 bupropion to moiphine. 98. The method of claim 94, wherein said subject is a human. 99. The method of claim 94, wherein 0.001 to 25 mg/kg per day of said opioid is administered. 100. The method of claim 99, wherein 0.005 to 10 mg/kg per day of said opioid is administered. 101. The method of claim 94, wherein said method comprises administering to said subject a combination consisting essentially of (i) an opioid and (iii) bupropion, wherein said combination is administered in a therapeutically effective amount. 102. A pharmaceutical composition comprising (i) an opioid and (ii) bupropion. 103. The pharmaceutical composition of claim 102, further comprising a pharmaceutically acceptable carrier. 104. The pharmaceutical composition of claim 102, wherein said opioid is present in a subtherapeutically effective amount. 105. The pharmaceutical composition of claim 102, wherein said opioid is moφhine. 106. The pharmaceutical composition of claim 105, comprising between about 15:1 and 5:1 bupropion to moφhine. 107. The pharmaceutical composition of claim 102, wherein said composition consists essentially of (i) an opioid and (ii) bupropion. 108. A kit comprising a (i) combination of an opioid and bupropion, and (ii) instructions for administering said combination to treat pain or nociception. 109. The kit of claim 108, wherein said opioid is present in a subtherapeutically effective amount. 110. The kit of claim 108, wherein said opioid is moφhine. 111. The kit of claim 110, wherein said combination comprises between about 15: 1 and 5:1 bupropion to moφhine. 112. The kit of claim 108, wherein said instructions comprise administering 0.001 to 25 mg/kg per day of said opioid. 113. The kit of claim 112, wherein said instructions comprise administering 0.005 to 10 mg/kg per day of said opioid. 114. The kit of claim 108, wherein said kit comprises a (i) combination consisting essentially of an opioid and bupropion, and (ii) instructions for administering said combination to treat pain or nociception.
法律状态
(WO2005107467) LEGAL DETAILS FOR WO2005107467  Actual or expected expiration date=2007-11-03    Legal state=DEAD    Status=LAPSED     Event publication date=2005-04-29  Event code=WO/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=WO WOUS2005015044  Application date=2005-04-29  Standardized application number=2005WO-US15044     Event publication date=2005-11-17  Event code=WO/A2  Event type=Examination events  International application published without international search report  Publication country=WO  Publication number=WO2005107467  Publication stage Code=A2  Publication date=2005-11-17  Standardized publication number=WO2005107467     Event publication date=2005-11-17  Event code=WO/AL  Event indicator=Pos  Event type=Designated states  Designated countries for regional patents GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG    Event publication date=2005-11-17  Event code=WO/AK  Event indicator=Pos  Event type=Designated states  Designated states AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KM KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW    Event publication date=2006-04-13  Event code=WO/A3  Event indicator=Pos  Event type=Examination events  Later publication of ISR with revised front page  Publication country=WO  Publication number=WO2005107467  Publication stage Code=A3  Publication date=2006-04-13  Standardized publication number=WO2005107467     Event publication date=2007-11-03  Event code=WO/EETL  Event type=Event indicating Not In Force  PCT Application validity period expired. LEGAL DETAILS FOR DESIGNATED STATE DE  Actual or expected expiration date=2006-11-04    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=DE     Event publication date=2006-11-04  Event code=WO/NENP  Event type=Event indicating Not In Force  Non-entry into the national phase in: Corresponding cc:  Designated or member state=DE     Event publication date=2006-11-04  Event code=WO/WWW  Event indicator=Neg  Event type=Event indicating Not In Force  Wipo information: withdrawn in national office Corresponding cc:  Designated or member state=DE
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