Opioid Composition for Treating Skin Lesions

• US 20120093929A1
• Filed: 05/05/2009
• Published: 04/19/2012
• Est. Priority Date: 05/05/2008
• Status: Active Grant

• Current Assignee: Euroceltique SA
• Original Assignee: Euroceltique SA
• Inventors: Oksche, Alexander, Prater, Derek, Walden, Malcolm, Mohammad, Hassan, Smith, Kevin J., Heath, Will, Kennedy, Bernard, Addison, Vanessa
• Granted Patent: US 9,782,359 B2
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to a composition, comprising (i) a matrix made of polymeric nanofibers, and (ii) an opioid agonist within the matrix.

Claims

1. A pharmaceutical composition, comprising

a) a matrix made of polymeric fibers, and

b) at least one opioid agonist and/or at least one pharmaceutically acceptable salt thereof.

2. The pharmaceutical composition of claim 1, wherein the matrix is a non-woven matrix of polymeric fibers.

3. The pharmaceutical composition of claim 1, wherein at least some of the polymeric fibers are made of a biodegradable polymer.

4. The pharmaceutical composition of claim 3, wherein the biodegradable polymer is selected from the group consisting of poly (lactic acid), poly (glycolic acid), poly (lactic-co-glycolic acid), poly (ε

-caprolactone), polyvinyl-caprolactame (PVCL), polyhydroxyalkanoates, poly(-caprolactone)-systems, poly (alkylene succinate), poly(ethylene/butylene succinate), poly(ethylene/butylene adipate), poly (β

-hydroxybutyrate-co-β

-hydroxyvalerate), hyaluronic acid, agarose, dextrose, cellulose, starch, chitin, gelatin, and any mixture thereof.

5. The pharmaceutical composition of claim 1, wherein at least some of the polymeric fibers are made of a non-biodegradable polymer.

6. The pharmaceutical composition of claim 5, wherein the non-biodegradable polymer is selected from the group consisting of poly(ethylene-co-vinyl acetate), polyvinyl acetate, polyvinyl pyrrolidone, polyurethane, and polyethylene terephthalate.

7. The pharmaceutical composition of claim 1, wherein the polymeric fibers are nanofibers.

8. The pharmaceutical composition of claim 7, wherein the polymeric nanofibers have an average fiber diameter in the range of from about 10 nm to about 500 nm.

9. The pharmaceutical composition of claim 1, wherein said at least one opioid agonist and/or at least one pharmaceutically acceptable salt thereof is within the said matrix made of polymeric fibers.

10. The pharmaceutical composition of claim 1, wherein the opioid agonist is selected from the group consisting of morphine, oxycodone, buprenorphine, hydromorphone, oxymorphone, propoxyphene, nicomorphine, dihydrocodeine, diamorphine, papaveretum, codeine, ethylmorphine, phenylpiperidine, methadone, dextropropoxyphene, buprenorphine, pentazocin, tilidine, etorphine, dihydroetorphine, tramadol, hydrocodone, loperamide, and any mixture thereof.

11. The pharmaceutical composition of claim 1, wherein the opioid agonist has a binding affinity to the opioid receptor and/or to the δ

opioid receptor.

12. The pharmaceutical composition of claim 11, wherein the opioid agonist is selected from norbuprenorphine, etorphine, dihydroetorphine, leu-enkephalin and its derivatives, met-enkephalin and its derivatives, and β

-endorphin and its derivatives.

13. The pharmaceutical composition of claim 1, wherein the opioid agonist is present in the form of a pharmaceutically acceptable salt.

14. The pharmaceutical composition of claim 1, wherein the matrix provides a controlled release of the at least one opioid agonist and/or of at least one pharmaceutically acceptable salt thereof from the pharmaceutical composition.

15. The pharmaceutical composition of claim 14, wherein the release follows substantially zero order release kinetics.

16. The pharmaceutical composition of claim 1, wherein the amount of the opioid agonist and/or pharmaceutically acceptable salt thereof and the release rate thereof are chosen to achieve topical efficacy only and to not allow for any substantial systemic uptake of the at least one opioid agonist and/or a pharmaceutically acceptable salt thereof.

17. The pharmaceutical composition of claim 1, further comprising one or more additional pharmaceutically active compounds.

18. The pharmaceutical composition of claim 1, wherein the composition is designed to cover a skin surface area in the range of from 1 cm² to 1000 cm².

19. The pharmaceutical composition of claim 1, further comprising one or more pharmaceutically acceptable excipients.

20. The pharmaceutical composition of claim 19, wherein said one or more pharmaceutically acceptable excipients comprise a plasticizer.

21. The pharmaceutical composition of claim 19, wherein said one or more pharmaceutically acceptable excipients comprise preservatives, antioxidants, and colorants.

22. The pharmaceutical composition of claim 1, wherein the composition is provided in the form of a patch, a wound dressing, or a gauze.

23. The composition of claim 1, wherein the said composition is used for the topical treatment of skin lesions.

24. The composition of claim 23, wherein the skin lesions result from ulcers, from skin graft donor sites, or from burns.

25. The composition of claim 24, wherein the skin lesions result from a venous leg ulcer or chronic leg ulcer.

26. The composition of claims 23, wherein the topical treatment includes treatment of pain, which results from skin lesions.

27. The composition of claim 23, wherein the topical treatment promotes wound healing of skin lesions.

28. A method of topically treating skin lesions, comprising topically applying a composition of claim 1 to said skin lesions.

29. The method of treating of claim 28, wherein the skin lesions result from ulcers, from skin graft donor sites, or from burns.

30. The method of treating of claim 41, wherein the leg ulcers are venous leg ulcer or chronic leg ulcer.

31. The method of treating of claim 28, wherein the topical treatment includes treatment of pain which results from skin lesions.

32. The method of treating of claim 28, wherein the topical treatment promotes wound healing of skin lesions.

33. A process for producing the matrix of claim 1 by electrospinning polymeric fibers to form a matrix.

34. The process for producing the matrix of claim 33, by electrospinning the fibers in the presence of the at least one opioid agonist and/or the pharmaceutically acceptable salt thereof.

35. The process for producing the matrix of claim 33, wherein the at least one opioid agonist and/or the pharmaceutically acceptable salt thereof is added to the matrix after electrospinning.

36. The pharmaceutical composition of claim 8, wherein the polymeric nanofibers have an average fiber diameter in the range of from about 20 to about 200 nm.

37. The pharmaceutical composition of claim 13, wherein the opioid agonist is present in the form of a pharmaceutically acceptable hydrochloride, sulfate, bisulfate, tartrate, nitrate, citrate, bitartrate, phosphate, malate, maleate, hydrobromide, hydroiodide, fumarate or succinate salt.

38. The pharmaceutical composition of claim 17, further comprising one or more additional pharmaceutically active compounds from the group of antiseptic agents, antibiotic agents, antifungal agents, antiviral agents, and anaesthetics.

39. The composition of claim 23, wherein the said composition is used for the topical treatment of open skin lesions.

40. The composition of claim 24, wherein the skin lesions result from decubitus ulcers, diabetic ulcers, leg ulcers, or pressure ulcers.

41. The method of treating of claim 28, wherein the said composition is topically applied to open skin lesions.

42. The method of treating of claim 29, wherein the skin lesions result from decubitus ulcers, diabetic ulcers, leg ulcers, or pressure ulcers.