Administration of sleep restorative agents

• US 20020165246A1
• Filed: 03/05/2002
• Published: 11/07/2002
• Est. Priority Date: 03/05/2001
• Status: Abandoned Application

• Current Assignee: Andrew Holman
• Original Assignee: Andrew Holman
• Inventors: Holman, Andrew
• Application Number:
  US10/091,744
• Publication Number:
  US 20020165246A1
• Time in Patent Office: Days
• US Class Current: 514/270
• 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 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/545 Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: , e.g. cephalosporins, cefaclor, or cephalexine
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present invention provides methods and compositions for increasing the efficacy of a therapeutic agent administered to a subject. A sleep restorative agent is co-administered to the subject along with the therapeutic agent, whereby the efficacy of the therapeutic agent is increased.

Claims

1. A method for increasing the efficacy of a therapeutic agent administered to a subject having an autoimmune condition, comprising co-administering to the subject an effective amount of a sleep restorative agent or a pharmacologically acceptable addition salt thereof, and a therapeutic agent;

whereby the efficacy of the therapeutic agent is increased.

2. The method of claim 1, wherein an undesired side effect associated with administration of the therapeutic agent is reduced.

3. The method of claim 1, wherein a symptom of the subject is reduced.

4. The method of claim 1, wherein administration of the sleep restorative agent spares the effective amount of the therapeutic agent.

5. The method of claim 1, wherein sleep quality of the subject is increased.

6. The method of claim 5, wherein increased sleep quality is manifested by restoration or prolongation of stage III/IV sleep, decreased sleep fragmentation or disruption, reduced sleep apnea, reduced restless legs syndrome, decreased restlessness, decreased racing thoughts, decreased talking in one'"'"'s sleep or decreased nightmares.

7. The method of claim 1, wherein excessive sympathetic tone in the subject is reduced.

8. The method of claim 1, wherein the sleep restorative agent is a compound of the following formula:

9. The method of claim 8, wherein, wherein the sleep restorative agent is 2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzo-thiazole or the (−

)-enantiomer thereof.

10. The method of claim 1, wherein the sleep restorative agent is a compound of the following formula:

11. The method of claim 10, wherein the sleep restorative agent is 4-[2-(dipropylamino)-ethyl]-1,3-dihydro-2H-indol-2-one.

12. The method of claim 1, wherein the sleep restorative agent is Lorazepam, Clonazepam, Tizanidine, Gabapentin, Zaleplon, Zolpidem, pregabalin, or pharmaceutically acceptable salts thereof.

13. The method of claim 1, wherein the therapeutic agent is soluble TNFα

receptor, methotrexate, prednisone, an interferon, a cyclosporin, an ascomycin, a rapamycin, a corticosteroid, a cyclophosphamide, azathioprine, brequinar, leflunomide, mizoribine, deoxyspergualin, or immunosuppressive monoclonal antibodies to a leukocyte receptor.

14. The method of claim 13, wherein the soluble TNFα

receptor is Etanercept or Lenercept.

15. The method of claim 1, wherein the sleep restorative agent and the therapeutic agent are administered in a unitary dosage form.

16. The method of claim 1, wherein the sleep restorative agent and the therapeutic agent are administered separately.

17. The method of claim 1, wherein the sleep restorative agent is administered as a dosage form of a tablet, capsule, lozenge, powder, solution, suspension, emulsion, injectable solution, syrup, suppository, or transdermal patch.

18. The method of claim 17, wherein the dosage form further comprises a pharmaceutically acceptable carrier.

19. The method of claim 1, wherein the therapeutic agent is an immunomodulatory agent.

20. A method for sparing an effective amount of a therapeutic agent administered to a subject having an autoimmune condition, comprising:

co-administering to the subject the therapeutic agent and an effective amount of a sleep restorative agent, the sleep restorative agent improving sleep quality of the subject;

whereby the sleep restorative agent spares the effective amount of the therapeutic agent.

21. The method of claim 20, wherein an undesired side effect associated with administration of the therapeutic agent is reduced.

22. The method of claim 20, wherein the autoimmune condition is rheumatoid arthritis;

psoriatic arthritis;

a spondyloarthropathy;

palindromic rheumatism;

systemic lupus erythematosus;

vasculitis with systemic lupus erythematosus;

multiple sclerosis;

Hashimoto'"'"'s thyroiditis;

chronic pseudogout;

hepatitis C arthritis, mixed connective tissue disease;

dermatomyositis, polymyositis;

scleroderma;

Sjogren'"'"'s syndrome;

cryoglobulinemia;

Crohn'"'"'s disease;

ulcerative colitis;

autoimmune hepatitis;

sclerosing cholangitis;

primary biliary cirrhosis;

autoimmune pneumonitis;

autoimmune cerebritis;

thyroiditis;

graft versus host disease;

Myasthenia gravis;

pemphigus vulgaris;

temporal arteritis;

polymyalgia rheumatica;

autoimmune hemolytic anemia;

idiopathic thrombocytopenic purpura;

thrombotic thrombocytopenic purpura;

hemolytic uremic syndrome;

Sweet'"'"'s syndrome;

polyarteritis nodosa;

microscopic polyarteritis nodosa;

amyloidosis;

sarcoidosis;

or familial Mediterranean fever.

23. The method of claim 22, wherein the spondyloarthropathy is Behcet'"'"'s disease, Whipple'"'"'s Disease, sarcoidosis, ankylosing spondylitis or Reiter'"'"'s Syndrome.

26. The method of claim 25, wherein the immunomodulatory agent is soluble TNFα

receptor, prednisone, methotrexate, an interferon, a cyclosporin, an ascomycin, a rapamycin, a corticosteroid, a cyclophosphamide, azathioprine, brequinar, leflunomide, mizoribine, deoxyspergualin, or immunosuppressive monoclonal antibodies to a leukocyte receptor.

27. The method of claim 26, wherein the immunomodulatory agent is soluble TNFα

receptor.

28. The method of claim 25, wherein the subject has a sleep disorder.

29. The method of claim 25, wherein a side effect associated with administration of the therapeutic agent is reduced.

24. A method for sparing an effective amount of a therapeutic agent administered to a subject having an autoimmune condition, comprising:

co-administering to the subject the therapeutic agent and an effective amount of a sleep restorative agent, the sleep restorative agent reducing excessive sympathetic tone of the subject;

whereby the sleep restorative agent spares the effective amount of the therapeutic agent.

25. A method for reducing a symptom in a subject in need of immunomodulatory therapy, comprising co-administering an effective amount of an immunomodulatory agent and an effective amount of a sleep restorative agent, the sleep restorative agent improving sleep quality of the subject;

whereby the sleep restorative agent spares the effective amount of the immunomodulatory agent needed to reduce the symptom.

30. A composition for administration to a subject having an autoimmune disease, comprising:

an effective amount of a sleep restorative agent; and

and an effective amount of a therapeutic agent;

the effective amount of the therapeutic agent spared by the sleep restorative agent.

31. The composition of claim 30, wherein the composition is a unitary dose.

32. The composition of claim 30, wherein the composition is administered as a tablet, capsule, lozenge, powder, solution, suspension, emulsion, injectable solution, syrup, suppository, or transdermal patch.

33. The composition of claim 30, wherein the composition further comprises a pharmaceutically acceptable carrier, an excipient or an adjuvant.

34. The composition of claim 30, wherein the sleep restorative agent is a compound of the following formula:

35. The method of claim 34, wherein, wherein the sleep restorative agent is 2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzo-thiazole or the (−

)-enantiomer thereof.

36. The method of claim 30, wherein the sleep restorative agent is a compound of the following formula:

37. The method of claim 36, wherein the sleep restorative agent is 4-[2-(dipropylamino)-ethyl]-1,3-dihydro-2H-indol-2-one.

38. The method of claim 30, wherein the sleep restorative agent is Lorazepam, Clonazepam, Tizanidine, Gabapentin, Zaleplon, Zolpidem, or pharmaceutically acceptable salts thereof.

39. The method of claim 30, wherein the therapeutic agent is soluble TNFα

receptor, methotrexate, prednisone, an interferon, a cyclosporin, an ascomycin, a rapamycin, a corticosteroid, a cyclophosphamide, azathioprine, brequinar, leflunomide, mizoribine, deoxyspergualin, or immunosuppressive monoclonal antibodies to a leukocyte receptor.