Opioid agonist antagonist combinations

• US 9,211,293 B2
• Filed: 12/17/2012
• Issued: 12/15/2015
• Est. Priority Date: 12/15/2011
• Status: Active Grant

• Current Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Original Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Inventors: Deaver, Daniel, Ehrich, Elliot
• Primary Examiner(s): Shibuya, Mark
• Assistant Examiner(s): Shiao, Yih-Horng
• Application Number:
  US13/717,128
• Publication Number:
  US 20130281388A1
• Time in Patent Office: 1,093 Days
• Field of Search: 514/27, 514/254.05, 514/255.05, 514/282, 514/289
• US Class Current: 1/1
• 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 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

The invention relates a composition comprising an opioid agonist and Compound-1:

Claims

1. A composition comprising a pharmaceutically effective amount of an opioid agonist and Compound-1:

2. The composition according to claim 1, wherein said opioid agonist is selected from the group consisting of morphine, codeine, hydromorphone, hydrocodone, oxycodone, oxymorphone, dihydrocodeine, dihydromorphine and tramadol.

3. A controlled release formulation comprising a composition according to claim 1.

4. The composition according to claim 1, further comprising an additional agent for treatment of depression selected from the group consisting of a selective serotonin re-uptake inhibitor, serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOIs) and tricyclic antidepressants, or an antidepressant compound belonging to the heterocyclic class.

5. The composition of claim 4, wherein said additional anti-depressant is selected from the group consisting of fluoxetine, norfluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram, bupropion, nefazodone, mirtazapine, venlafaxine, duloxetine, milnacipran, reboxetine, zimelidine, indalpine, gepirone, femoxetine and alaproclate.

6. A unit dosage form comprising a composition according to claim 1.

7. The composition according to claim 1, wherein the molar ratio of Compound-1:

agonist is about 0.9-1.3;

1.0.

8. A method of treating a depressive disorder comprising the step of administering Compound-1 in combination with a partial opioid agonist according to claim 1 to a patient in need thereof:

9. The method according to claim 8, wherein said depressive disorder is selected from the group consisting of major depressive disorder, chronic depression, severe unipolar recurrent major depressive episodes, dysthymic disorder, depressive neurosis and neurotic depression, melancholic depression, atypical depression, reactive depression, treatment resistant depression, seasonal affective disorder and pediatric depression;

premenstrual syndrome, premenstrual dysphoric disorder, hot flashes, bipolar disorders or manic depression, bipolar I disorder, bipolar II disorder and cyclothymic disorder.

10. The method according to claim 9, wherein said depressive disorder is major depressive disorder.

11. The method according to claim 10, wherein said major depressive disorder is resistant to two or more antidepressants.

12. The method according to claim 11, wherein the antidepressants are selected from the group consisting of selective serotonin reuptake inhibitors (SSRIs), Serotonin-norepinephrine reuptake inhibitors (SNRIs), Monoamine oxidase inhibitors (MAOIs) and Tricyclic antidepressants.

13. The method according to claim 8, wherein said depressive disorder is treatment resistant depression.

14. The method according to claim 8, wherein said subject exhibits one or more depressive symptoms selected from the group consisting of irritability, feelings of hopelessness and helplessness, inability to concentrate, sadness, insomnia, appetite loss, lack of interest in life'"'"'s activities, thoughts of suicide, dizziness, nausea, vomiting, hyperhidrosis, menorrhagia, pain in extremity, constipation, sedation, fatigue, feeling abnormal, flushing and somnolence.

15. The method according to claim 8, wherein the molar ratio of Compound-1:

agonist is about 0.9-1.3;

1.0.

16. A method of treating an opioid receptor mediated disease or disorder comprising the step of administering pharmaceutically effective amounts of Compound-1 in combination with an opioid agonist according to claim 1 to a patient in need thereof:

17. The composition according to claim 1, further comprising a pharmaceutically acceptable carrier.

18. The method according to claim 16 wherein said disease or disorder is pain.

19. The composition according to claim 1 wherein said agonist is methadone.