Methods and compositions for treating or preventing sleep disturbances and associated illnesses using very low doses of cyclobenzaprine

• US 20010046988A1
• Filed: 06/27/2001
• Published: 11/29/2001
• Est. Priority Date: 08/13/1999
• Status: Active Grant

• Current Assignee: Krele Pharmaceuticals, Inc. (Tonix Pharmaceuticals Holding Corp.)
• Original Assignee: Vela Pharmaceuticals Inc. (W World Corp.)
• Inventors: Iglehart, Iredell W.
• Granted Patent: US 6,541,523 B2
• Time in Patent Office: Days
• US Class Current: 514/221
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/02 Immunomodulators

Abstract

The present invention relates to methods and compositions comprising a very low dose of cyclobenzaprine or metabolite thereof for preventing and treating sleep disturbances and illnesses manifested with sleep dysfunction including fibromyalgia syndrome, chronic fatigue syndrome, sleep disorders, psychogenic pain disorders or chronic pain syndromes or symptoms thereof. The present invention further relates to methods and compositions for treating sleep disturbances, chronic pain or fatigue in humans suffering from fibromyalgia syndrome, chronic fatigue syndrome, sleep disorders, psychogenic pain disorders, chronic pain syndromes using a very low dose of cyclobenzaprine.

Claims

1. A method for treating or preventing a sleep disturbance comprising the step of administering to a human in need of treatment for such sleep disturbance a composition comprising cyclobenzaprine or a metabolite, prodrug, or salt thereof in an amount of less than 5 mg/day.

2. The method according to

claim 1

, wherein the sleep disturbance is associated with the group consisting of fibromyalgia syndrome, prolonged fatigue, chronic fatigue, chronic fatigue syndrome, a sleep disorder, a psychogenic pain disorder, and chronic pain syndrome (type II).

3. The method according to

claim 1

, wherein such sleep disturbance is associated with the administration of a drug.

4. The method according to

claim 3

wherein the drug is a benzodiazepine.

5. The method according to

claim 4

wherein the benzodiazepine is selected from the group comprising chlordiazepoxide, clorazepate, diazepam, flurazepam, halazepam, prazepam, alprazolam, chlonazepam, flunitrazepam, lorazepam, midazolam, oxazepam, quazepam, temazepam, or troazolam.

6. The method according to

claim 3

wherein the drug causing sleep disturbance is a barbiturate.

7. The method according to

claim 6

wherein the barbiturate is selected from the group including phenobarbital, amobarbital, aprobarbital, butabarbital, mephobarbital, pentobarbital, secobarbital, and talbutal.

8. The method according to

claim 3

wherein the drug is alcohol.

9. The method according to

claim 1

, wherein the human is suffering from an autoimmune disease.

10. The method according to

claim 1

, wherein the human is suffering from or is expecting to suffer stress or anxiety.

16. The method according to any one of claims 1 or 11-15, wherein cyclobenzaprine or metabolite thereof is administered in an amount of 2.5 mg or less per day.

17. The method according to any one of claims 1 or 11-15, wherein cyclobenzaprine or metabolite thereof is administered in an amount of 1.0 mg or less per day.

18. The method according to any one of claims 1 or 11-15, wherein cyclobenzaprine or metabolite thereof is administered in one dose before bedtime.

19. The method according to any one of claims 1 or 11-15, wherein cyclobenzaprine or metabolite thereof is administered in combination with psychotherapy.

20. The method according to any one of claims 1 or 11-15, wherein cyclobenzaprine or metabolite thereof is administered in combination with light-box therapy.

21. The method according to any one of claims 1 or 11-15, wherein cyclobenzaprine or metabolite thereof is administered in combination with other drug therapies for treatment of the illness or symptoms thereof.

22. The method according to any one of claims 1 or 11-15, wherein cyclobenzaprine is administered as a hydrochloride salt.

23. The method according to any one of claims 1 or 11-15, further comprising the step of administering a therapeutic agent sequentially or concurrently with said cyclobenzaprine or metabolite thereof.

24. The method according to

claim 21

, wherein the therapeutic agent is selected from the group consisting of a TCA, an SSRI, an atypical antidepressant, an SNRI, an NRIS, an anti-inflammatory, or an analgesic.

25. The method according to

claim 24

, wherein the TCA is selected from the group consisting of imipramine, trimipramine, nortriptyline, amitriptyline, doxepin, protriptyline, clomipramine and desipramine.

26. The method according to

claim 24

, wherein the SSRI is selected from the group consisting of fluoxetine, fluvoxamine maleate, paroxetine, sertraline, and citalopram.

27. The method according to

claim 24

, wherein the atypical antidepressant is selected from the group consisting of serotonin agonist and reuptake inhibitors (SARIs) such as nefazodone (Serzone™

) or trazodone (Desyrel™

);

Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs) such as bupropion (Wellbutrin™

); and

norepinephrine reuptake inhibitors (NRIs) such as reboxetine (Edronax™

) and serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor™

), amoxapine and maprotiline.

28. The method according to any one of claims 1 or 11-15, wherein the cyclobenzaprine or metabolite thereof is administered orally or parentally.

29. The method according to any one of claims 1 or 11-15, wherein the cyclobenzaprine or pharmaceutically acceptable salt thereof is administered as a tablet or a capsule.

11. A method for treating or preventing fibromyalgia comprising the step of administering to a human in need of treatment for fibromyalgia cyclobenzaprine or a metabolite thereof in an amount of less than 5 mg/day.

12. A method for treating or preventing prolonged fatigue, chronic fatigue or chronic fatigue syndrome comprising administering to a human in need of treatment for prolonged fatigue, chronic fatigue or chronic fatigue syndrome, cyclobenzaprine or a metabolite thereof in an amount of less than 5 mg/day.

13. A method for treating or preventing a sleep disorder comprising the step of administering to a human in need of treatment for a sleep disorder cyclobenzaprine or a metabolite thereof in an amount of less than 5 mg/day.

14. A method for treating or preventing a psychogenic pain disorder comprising the step of administering to a human in need of treatment for a psychogenic pain disorder cyclobenzaprine or a metabolite thereof in an amount of less than 5 mg/day.

15. A method for treating or preventing a chronic pain syndrome (type II) comprising the step of administering to a human in need of treatment for a chronic pain syndrome (type II) cyclobenzaprine or a metabolite thereof in an amount of less than 5 mg/day.

30. A composition comprising less than 5 mgs of cyclobenzaprine or a metabolite thereof as a single unit or as a unit that is pre-prepared into separable portions, each portion of which comprises a less than 5 mgs of cyclobenzaprine or metabolite thereof.

31. The composition according to

claim 30

, wherein the single unit or each separable portion comprises less than or equal to 2.5 mg of cyclobenzaprine or metabolite thereof.

32. The composition according to

claim 30

, wherein the single unit or each separable portion comprises less than or equal to 1.0 mg of cyclobenzaprine or metabolite thereof.

33. The composition according to

claim 30

, further comprising a therapeutic agent.

34. The composition according to

claim 33

, wherein the therapeutic agent is selected from the group consisting of a TCA, an SSRI, an atypical antidepressant, an SNRI, an NRIS an anti-inflammatory, or an analgesic.

35. The composition according to

claim 34

, wherein the therapeutic agent is a TCA selected from the group consisting of imipramine, trimipramine, nortriptyline, amitriptyline, doxepin, protriptyline, clomipramine and desipramine.

36. The composition according to

claim 34

, wherein the therapeutic agent is an SSRI selected from the group consisting of fluoxetine, fluvoxamine, paroxetine, sertraline or citalopram.

37. The composition according to

claim 34

, wherein the atypical antidepressant is selected from the group consisting of serotonin agonist and reuptake inhibitors (SARIs) such as nefazodone (Serzone™

) or trazodone (Desyrel™

);

Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs) such as bupropion (Wellbutrin™

); and

norepinephrine reuptake inhibitors (NRIs) such as reboxetine (Edronax™

) and serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor™

), amoxapine and maprotiline.