Methods for treatment of cognitive and menopausal disorders with D-threo methylphenidate

• US 7,115,631 B2
• Filed: 07/16/2002
• Issued: 10/03/2006
• Est. Priority Date: 12/04/1995
• Status: Expired due to Fees

• Current Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Original Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Inventors: Sterling, David, Khetani, Vikram, Zeitlin, Andrew L., Dariani, Maghsoud M., Faleck, Herbert J., Zeldis, Jerome B
• Primary Examiner(s): Henley, III, Raymond J
• Application Number:
  US10/195,974
• Publication Number:
  US 20020198234A1
• Time in Patent Office: 1,540 Days
• Field of Search: 514/315, 514/317
• US Class Current: 514/317
• 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 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/12 for climacteric disorders
• 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 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 211/34 with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C12P 17/12 containing a six-membered hetero ring
• CPC Class Codes: C12P 41/006 by reactions involving C-N bonds, e.g. nitriles, amides, hydantoins, carbamates, lactames, transamination reactions, or keto group formation from racemic mixtures

Abstract

In one aspect, the present invention is directed to methods for treating fatigue, neurobehavioral slowing and other cognitive disorders and defects due to cancers and treatments associated with cancers, and similar conditions. In a further aspect, the present invention is directed to methods for treating disorders related to menopause, including executive function defects. The methods involve the administration of a composition comprising D-threo methylphenidate that is substantially free of L-threo methylphenidate and of erythro forms of methylphenidate.

Claims

1. A method for alleviating fatigue arising from an oncological condition, said method comprising the steps of:

identifying a patient suffering from said fatigue, and

administering to said patient a unit dosage comprising a compound having the formula

or a pharmaceutically acceptable salt thereof, wherein R₁ is C₁-C₄ alkyl, and R₂ is hydrogen or C₁-C₄ alkyl, in a pharmaceutically acceptable carrier or diluent, said dosage having less than 10% by weight of other stereoisomers of the compound or salt.

2. The method of claim 1 wherein the unit dosage is 1% to about 90% by weight of active ingredient.

3. The method of claim 1 wherein the unit dosage is 20% to about 90% by weight of active ingredient.

4. The method of claim 1 wherein the unit dosage is in a form suitable for oral administration.

5. The method of claim 1 wherein said oncological condition is a cancer selected from the group consisting of solid tumors and nonsolid tumors.

6. The method of claim 1 wherein said oncological condition is a solid tumor.

51. The method of claim 1 wherein said administration of said compound gives rise to efficacious treatment without interfering with patient sleep patterns or engendering anoretic behavior.

7. A method for alleviating fatigue arising from the administration of a treatment for an oncological condition, said method comprising the steps of:

identifying a patient suffering from said fatigue, and

administering to said patient a unit dosage comprising a compound having the formula

or a pharmaceutically acceptable salt thereof, wherein R₁ is C₁-C₄ alkyl, and R₂ is hydrogen or C₁-C₄ alkyl, in a pharmaceutically acceptable carrier or diluent, said dosage having less than 10% by weight of other stereoisomers of the compound or salt.

8. The method of claim 7 wherein the unit dosage is 1% to about 90% by weight of active ingredient.

9. The method of claim 7 wherein the unit dosage is 20% to about 90% by weight of active ingredient.

10. The method of claim 7 wherein the unit dosage is in a form suitable for oral administration.

11. The method of claim 7 wherein said treatment for said oncological condition is chemotherapy or radiation therapy.

12. The method of claim 7 wherein said treatment for said oncological condition is chemotherapy.

52. The method of claim 7 wherein said administration of said compound gives rise to efficacious treatment without interfering with patient sleep pattern or engendering anoretic behavior.

13. A method for alleviating neurobehavioral slowing arising from an oncological condition, said method comprising the steps of:

identifying a patient suffering from said neurobehavioral slowing, and

administering to said patient a unit dosage comprising a compound having the formula

or a pharmaceutically acceptable salt thereof, wherein R₁ is C₁-C₄ alkyl, and R₂ is hydrogen or C₁-C₄ alkyl, in a pharmaceutically acceptable carrier or diluent, said dosage having less than 10% by weight of other stereoisomers of the compound or salt.

14. The method of claim 13 wherein the unit dosage is 1% to about 90% by weight of active ingredient.

15. The method of claim 13 wherein the unit dosage is 20% to about 90% by weight of active ingredient.

16. The method of claim 13 wherein the unit dosage is in a form suitable for oral administration.

17. The method of claim 13 wherein said oncological condition is a cancer selected from the group consisting of solid tumors and nonsolid tumors.

18. The method of claim 13 wherein said oncologicaI condition is a solid tumor.

53. The method of claim 13 wherein said administration of said compound gives rise to efficacious treatment without nterfering with patient sleep patterns or engendering anoretic behavior.

19. A method for alleviating neurobehavioral slowing arising from the administration of a treatment for an oncological condition, said method comprising the steps of:

identifying a patient suffering from said neurobehavioral slowing, and

administering to said patient a unit dosage comprising a compound having the formula

or a pharmaceutically acceptable salt thereof, wherein R₁ is C₁-C₄ alkyl, and R₂ is hydrogen or C₁-C₄ alkyl, in a pharmaceutically acceptable carrier or diluent, said dosage having less than 10% by weight of other stereoisomers of the compound or salt.

20. The method of claim 19 wherein the unit dosage is 1% to about 90% by weight of active ingredient.

21. The method of claim 19 wherein the unit dosage is 20% to about 90% by weight of active ingredient.

22. The method of claim 19 wherein the unit dosage is in a form suitable for oral administration.

23. The method of claim 19 wherein said treatment for said oncological condition is chemotherapy or radiation therapy.

24. The method of claim 19 wherein said treatment for said oncological condition is chemotherapy.

25. The method of claim 19 wherein said oncological condition is a cancer selected from the group consisting of solid tumors and nonsolid tumors.

26. The method of claim 19 wherein said oncological condition is a solid tumor.

54. The method of claim 19 wherein said administration of said compound gives rise to efficacious treatment without interfering with patient sleep patterns or engendering anoretic behavior.

27. A method for alleviating a cognitive side effect of a treatment for an oncological condition, comprising the steps of:

identifing a patient suffering from a cognitive side-effect of a treatment for an oncological condition; and

administering to said patient a unit dosage comprising a compound having the formula

or a pharmaceutically acceptable salt thereof, wherein R₁ is C₁-C₄ alkyl, and R₂ is hydrogen or C₁-C₄ alkyl, in a pharmaceutically acceptable carrier or diluent, said dosage having less than 10% by weight of other stereoisomers of the compound or salt.

28. The method of claim 27 wherein the unit dosage is 1% to about 90% by weight of active ingredient.

29. The method of claim 27 wherein the unit dosage is 20% to about 90% by weight of active ingredient.

30. The method of claim 27 wherein the unit dosage is in a form suitable for oral administration.

31. The method of claim 27 wherein said oncological condition is a cancer selected from the group consisting of solid tumors and nonsolid tumors.

32. The method of claim 27 wherein said oncological condition is a solid tumor.

33. The method of claim 27 wherein said treatment for said oncological condition is the administration of pain relief medication, chemotherapy, radiation therapy, or surgery.

34. The method of claim 27 wherein said treatment for said oncological condition is the administration of pain relief medication.

35. The method of claim 34 wherein said pain relief medication is and opioid analgesic.

36. The method of claim 27 wherein said cognitive side effect is sedation, decreased cognitive function, major depressive disorder, or neurobehavioral slowing.

37. The method of claim 36 wherein said cognitive side effect is sedation, decreased cognitive function or neurobehavioral slowing.

38. The method of claim 36 wherein said cognitive side effect is sedation.

55. The method of claim 27 wherein said administration of said compound gives rise to efficacious treatment without interfering with patient sleep patterns or engendering anoretic behavior.

39. A method for treating a symptom of menopause comprising the steps of:

identifing a patient suffering from a symptom of menopause; and

administering to said patient a unit dosage comprising a compound having the formula

or a pharmaceutically acceptable salt thereof, wherein R₁ is C₁-C₄ alkyl, and R₂ is hydrogen or C₁-C₄ alkyl, in a pharmaceutically acceptable carrier or diluent, said dosage having less than 10% by weight of other stereoisomers of the compound or salt.

40. The method of claim 39 wherein the unit dosage is 1% to about 90% by weight of active ingredient.

41. The method of claim 39 wherein the unit dosage is 20% to about 90% by weight of active ingredient.

42. The method of claim 39 wherein the unit dosage is in a form suitable for oral administration.

43. The method of claim 39 wherein said symptom of menopause is decreased cognitive function.

44. The method of claim 39 wherein said symptom of menopause is vasomotor instability.

45. The method of claim 39 wherein said symptom of menopause is nervousness.

46. The method of claim 39 wherein said symptom of menopause is mental depression.

47. The method of claim 39 wherein said symptom of menopause is excitability.

48. The method of claim 39 wherein said symptom of menopause is fatigue.

49. The method of claim 39 wherein said symptom of menopause is apathy.

50. The method of claim 39 wherein said symptom of menopause is impairment of short term memory.

56. The method of claim 39 wherein said administration of said compound gives rise to efficacious treatment without interfering with patient sleep patterns or engendering anoretic behavior.