Method for treating pain

• US 5,945,416 A
• Filed: 03/24/1997
• Issued: 08/31/1999
• Est. Priority Date: 03/25/1996
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Womer, Daniel E., Shannon, Harlan E.
• Primary Examiner(s): Criares, Theodore J.
• Application Number:
  US08/823,461
• Time in Patent Office: 890 Days
• Field of Search: 514/220
• US Class Current: 514/220
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/54 having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 31/621 having the hydroxy group in position 2 esterified, e.g. benorylate
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The present invention provides a method for treating pain using a composition comprising olanzapine and Drug Useful in the Treatment of Pain.

Claims

1. A composition for treating pain comprising olanzapine or a pharmaceutically acceptable salt or solvate thereof;

and one or more Drug Useful in the Treatment of Pain in a weight ratio of from about one part olanzapine to from about one (1) part to about one thousand (1000) parts Drug Useful in the Treatment of Pain.

2. A composition of claim 1 wherein the Drug Useful in the Treatment of Pain is an NSAIDS.

3. A composition of claim 2 wherein the NSAIDS is selected from the group consisting of aspirin, indomethacin, ibuprofen, naproxen, fenoprofen, tolmetin, sulindac, meclofenamate, keoprofen, piroxicam, flurbiprofen, and diclofenac or a pharmaceutically acceptable salt thereof.

4. A composition of claim 1 wherein olanzapine is Form II olanzapine polymorph having a typical x-ray diffraction pattern as follows, wherein d represents the interplanar spacing:

space="preserve" listing-type="tabular">______________________________________ ______________________________________ 10.2689 8.577 7.4721 7.125 6.1459 6.071 5.4849 5.2181 5.1251 4.9874 4.7665 4.7158 4.4787 4.3307 4.2294 4.141 3.9873 3.7206 3.5645 3.5366 3.3828 3.2516 3.134 3.0848 3.0638 3.0111 2.8739 2.8102 2.7217 2.6432 2.6007. ______________________________________

5. A composition of claim 4 wherein the Drug Useful in the Treatment of Pain is selected from the group consisting of aspirin, ibuprofen, and naproxen.

6. A composition of claim 1 wherein the weight ratio of olanzapine to Drug Useful in the Treatment of Pain is from about one part olanzapine to from about one (1) to about one hundred (100) parts Drug Useful in the Treatment of Pain.

7. A composition of claim 6 wherein the weight ratio is from about one part olanzapine to from about one (1) to about thirty (30) parts Drug Useful in the Treatment of Pain.

8. A composition of claim 7 wherein the weight ratio is from about one part olanzapine to from about one (1) to about ten (10) parts Drug Useful in the Treatment of Pain.

9. A composition of claim 8 wherein the Drug Useful in the Treatment of Pain is selected from the group consisting of morphine, acetaminophen, ibuprofen, and diclofenac.

10. A composition of claim 1 wherein the Drug Useful in the Treatment of Pain is an opioid compound.

11. A composition of claim 4 wherein the Drug Useful in the Treatment of Pain is an opioid compound.

12. A composition of claim 7 wherein the Drug Useful in the Treatment of Pain is an opioid compound.

13. A composition of claim 10 wherein the opioid compound is selected from the group consisting of morphine, codeine, meperidine, methadone, propoxyphene, levorphanol, hydromorphone, oxymorphone, oxycodone, brompton'"'"'s cocktail, pentazocine, butorphanol, nabuphine, and buprenorphine.

14. A composition of claim 13 wherein the opioid compound is selected from the group consisting of morphine, oxymorphine, oxycodone, hydromorphine, codeine, and methadone.

15. A composition of claim 1 wherein the Drug Useful in the Treatment of Pain is selected from the group consisting of Tylenol #3, tricyclic antidepressants (for example desipramine, imipramine, amytriptiline, nortriptiline), anticonvulsants (for example, carbamazepine, gatapentine, valproate), and serotonin reuptake inhibitors (for example, fluoxetine, paroxetine, citalopram, sertraline), mixed serotonin-norepinephrine reuptake inhibitors (for example venlafaxine, duloxetine), serotonin receptor agonists and antagonists, cholinergic (muscarinic and nicotinic) analgesics, and neurokinin antagonists.

16. A composition of claim 4 wherein the Drug Useful in the Treatment of Pain is selected from the group consisting of Tylenol #3, tricyclic antidepressants, anticonvulsants, and serotonin reuptake inhibitors, mixed serotonin-norepinephrine reuptake inhibitors analgesics, and neurokinin antagonists.

17. A composition of claim 16 wherein the Drug Useful in the Treatment of Pain is a tricyclic antidepressant.

18. A composition of claim 1 wherein the Drug Useful in the Treatment of Pain is an alpha adrenergic compound.

19. A composition of claim 18 central alpha-adrenergic active compound is Clonidine or a pharmaceutically acceptable salt thereof.

20. A composition of claim 4 wherein the Drug Useful in the Treatment of Pain is an alpha adrenergic compound.

21. A composition of claim 7 wherein the Drug Useful in the Treatment of Pain is an alpha adrenergic compound.

22. A composition of claim 1 wherein the composition can provide a synergistic analgesic effect.

23. A composition for treating pain comprising olanzapine, or a pharmaceutically acceptable salt or solvate thereof, and ibuprofen, or a pharmaceutically acceptable salt thereof, in a weight ratio of about one part olanzapine to from about one (1) to about one thousand (1000) parts ibuprofen.

24. A composition of claim 23 wherein the olanzapine is Form II olanzapine polymorph.

25. A composition of claim 23 wherein the weight ratio is about one part olanzapine to from about one (1) to about one hundred (100) parts ibuprofen.

26. A composition of claim 23 wherein the weight ratio is about one part olanzapine to from about one (1) to about thirty (30) parts ibuprofen.

27. A composition of claim 26 wherein the weight ratio is about one part olanzapine to from about one (1) to about ten (10) parts ibuprofen.

28. A method for treating pain comprising administering an analgesic dose of a composition comprising olanzapine or a pharmaceutically acceptable salt or solvate thereof;

and one or more Drug Useful in the Treatment of Pain in a weight ratio of olanzapine to Drug Useful in the Treatment of Pain of from about one part olanzapine to from about one (1) to about one thousand (1000) parts Drug Useful in the Treatment of Pain.

29. A method of claim 28 wherein the Drug Useful in the Treatment of Pain is an NSAIDS.

30. A method of claim 28 wherein the weight ratio of olanzapine to Drug Useful in the Treatment of Pain is from about one (1) part olanzapine to from about one (1) to about one hundred (100) parts Drug Useful in the Treatment of Pain.

31. A method of claim 28 wherein the weight ratio of olanzapine to Drug Useful in the Treatment of Pain is from about one (1) part olanzapine to from about one (1) to about thirty (30) parts Drug Useful in the Treatment of Pain.

32. A method of claim 28 wherein olanzapine is Form II olanzapine polymorph having a typical x-ray diffraction pattern as follows, wherein d represents the interplanar spacing:

space="preserve" listing-type="tabular">______________________________________ ______________________________________ 10.2689 8.577 7.4721 7.125 6.1459 6.071 5.4849 5.2181 5.1251 4.9874 4.7665 4.7158 4.4787 4.3307 4.2294 4.141 3.9873 3.7206 3.5645 3.5366 3.3828 3.2516 3.134 3.0848 3.0638 3.0111 2.8739 2.8102 2.7217 2.6432 2.6007. ______________________________________

33. A method of claim 28 wherein the Drug Useful in the Treatment of Pain is selected from the group consisting of alpha adrenergic compounds and opioid compounds.

34. A method of claim 28 wherein the Drug Useful in the Treatment of Pain is selected from the group consisting of Tylenol #3, tricyclic antidepressants, anticonvulsants, and serotonin reuptake inhibitors, mixed serotonin-norepinephrine reuptake inhibitors analgesics, and neurokinin antagonists.

35. A method of claim 28 wherein pain is neuropathic pain.

36. A method of claim 28 wherein pain is nociceptive pain.

37. A method of claim 28 wherein the pain is acute pain.

38. A method for treating pain comprising administering an analgesic dose of a composition comprising olanzapine, or a pharmaceutically acceptable salt or solvate thereof, and ibuprofen, or a pharmaceutically acceptable salt thereof, in a weight ratio of about one part olanzapine to from about one (1) to about one thousand (1000) parts ibuprofen.

39. A method of claim 38 wherein the olanzapine is Form II olanzapine polymorph.

40. A method of claim 38 wherein the weight ratio of olanzapine to ibuprofen is about one (1) part olanzapine to from about one (1) to about one hundred (100) parts ibuprofen.

41. A method of claim 40 wherein the weight ratio of olanzapine to ibuprofen is about one (1) part olanzapine to from about one (1) to about thirty (30) parts ibuprofen.

42. A method of claim 38 wherein the pain is neuropathic pain.

43. A method of claim 38 wherein the pain is nociceptive pain.

44. A method of claim 38 wherein the pain is acute pain.