Compositions of buprenorphine and μ antagonists

• US 8,822,488 B2
• Filed: 12/14/2012
• Issued: 09/02/2014
• 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): Weddington, Kevin E
• Application Number:
  US13/715,198
• Publication Number:
  US 20130190342A1
• Time in Patent Office: 627 Days
• Field of Search: 514/282
• US Class Current: 514/282
• 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 31/4748 forming part of bridged ring systems strychnine A61K31/475; morphinan derivatives A61K31/485
• 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
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• 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 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The invention relates to a composition comprising buprenorphine and a μ opioid receptor antagonist, wherein the composition is characterized by an Agonist Antagonist Activity Index (AAnAI) of between about 0.7 and about 2.2; wherein;

$\mathrm{AAnAI}=\frac{\left[\frac{C_{\max \left(\mathrm{BUB}\right)}}{{\mathrm{BC}}_{30}}\right]}{\left[\frac{C_{\max \left(\mathrm{ANTAGONIST}\right)}}{{\mathrm{IC}}_{30}}\right]}.$

Claims

1. A composition comprising buprenorphine and a μ

opioid receptor antagonist, wherein the composition is characterized by an Agonist Antagonist Activity Index (AAnAI) of between about 0.7 and about 2.2;

wherein;

2. The composition according to claim 1, wherein said AAnAI is between about 0.8 and about 2.1, or between about 0.9 and about 2.0, or between about 1.0 and about 1.8, or between about 1.1 and about 1.6, or between about 1.2 and about 1.4.

3. The composition according to claim 1, wherein said antagonist is a compound of Formula I:

4. The composition according to claim 3, wherein said antagonist is a compound of Formula II:

5. The composition according to claim 4, wherein said antagonist is selected from:

9. A composition according to claim 3, wherein said compound of Formula I is:

21. A composition according to claim 1, wherein said composition has an AAnAI of about 1.3.

6. A composition comprising buprenorphine and a compound of Formula I:

7. The composition according to claim 6, wherein said compound of Formula I is a compound of Formula II:

8. The composition according to claim 6, wherein said compound of Formula I is selected from:

10. A composition comprising about 1 mg to about 100 mg of buprenorphine and about 0.25 to about 100 mg of a compound of Formula I.

11. The composition of claim 10 comprising about 2 mg to about 50 mg of buprenorphine.

12. The composition of claim 10 comprising about 3 to about 25 mg of buprenorphine.

13. The composition of claim 10 comprising about 3 to about 10 mg of buprenorphine.

14. The composition according to claim 11 comprising about 0.25 to about 50 mg of a compound of Formula I.

15. The composition according to claim 10 comprising about 0.5 to about 25 mg of a compound of Formula I.

16. The composition according to claim 10 comprising about 1.0 to about 20 mg of a compound of Formula I.

17. The composition according to claim 10 comprising about 2.0 to about 10 mg of a compound of Formula I.

18. The composition according to claim 10 wherein said compound of Formula I is a compound of Formula II.

19. The composition according to claim 10 wherein said compound of Formula I is selected from:

20. The composition according to claim 10, wherein said compound of Formula I is: