Methods and compositions for treating pain of the mucous membrane

• US 6,509,028 B2
• Filed: 06/17/2002
• Issued: 01/21/2003
• Est. Priority Date: 06/26/2000
• Status: Expired due to Term

• Current Assignee: Memorial Sloan-Kettering Cancer Center
• Original Assignee: Epicept Corporation (Immune Pharmaceuticals Inc.)
• Inventors: Zhang, Feng, Pasternak, Gavril W., Koleng, John J., Kolesnikov, Yuri A., Williams, Robert O.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): FUBARA, BLESSING M
• Application Number:
  US10/172,455
• Publication Number:
  US 20020192288A1
• Time in Patent Office: 218 Days
• Field of Search: 424/489, 424/434, 424/435, 424/443, 424/444, 424/445, 424/446, 424/447, 424/448, 424/449, 514/716, 514/626, 514/772, 514/817, 514/818, 514/900
• US Class Current: 424/434
• 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 31/445 Non condensed piperidines, e.g. piperocaine
• 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 9/0043 Nose
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• 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 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Compositions useful for long-lasting pain relief from mucosal damage, such as mucosal inflamation, abrasions, ulcerations, lesions, trauma and incisions, without significant systemic absorption. The compositions of the invention are particularly suitable for application to the mucous membrane of the nasal cavity and buccal cavity. To relieve pain, the compositions or the invention are topically applied directly to the affected area.

Claims

1. A composition comprising a mucoadhesive, a local anesthetic or a pharmaceutically-acceptable salt thereof, and an opioid or a pharmaceutically-acceptable salt thereof, wherein the mucoadhesive is a block copolymer of ethylene oxide and propylene oxide.

2. The composition of claim 1, wherein an amount of the local anesthetic is within a range of from about 0.01 percent to about 0.5 percent of a total weight of the composition.

3. The composition of claim 1, wherein an amount of the opioid is within a range of from about 0.05 percent to about 1 percent of a total weight of the composition.

4. The composition of claim 1, wherein an amount of the mucoadhesive is within a range of from about 0.1 percent to about 40 percent of a total weight of the composition.

5. The composition of claim 4, wherein an amount of the mucoadhesive is within a range of from about 15 percent to about 25 percent of a total weight of the composition.

6. The composition of claim 1, wherein the mucoadhesive is a block copolymer of ethylene oxide and propylene oxide of a formula I:

wherein x is an integer having an average value ranging from about 2 to about 128;

y is an integer having an average value ranging from about 14 to about 80; and

z is an integer having an average value ranging from 2 to about 128.

7. The composition of claim 1, wherein the mucoadhesive is poloxamer 407.

8. The composition of claim 1, wherein the local anesthetic is lidocaine, tetracaine, bupivacaine, prilocaine, mepivacaine, procaine, chloroprocaine, ropivacaine, dibucaine, etidocaine, benzocaine, a pharmaceutically-acceptable salt thereof, or a mixture thereof.

9. The composition of claim 8, wherein the local anesthetic is lidocaine or a pharmaceutically-acceptable salt thereof.

10. The composition of claim 1, wherein the opioid is morphine or loperamide or a pharmaceutically-acceptable salt thereof.

11. The composition of claim 10, wherein the opioid is morphine or a pharmaceutically-acceptable salt thereof.

12. A container adapted for topical application containing a composition comprising a mucoadhesive, a local anesthetic or a pharmaceutically-acceptable salt thereof, and an opioid or a pharmaceutically-acceptable salt thereof, wherein the mucoadhesive is a block copolymer of ethylene oxide and propylene oxide.

13. The container of claim 12, packaged in association with instructions, the instructions comprising:

topically applying the composition onto a mucous membrane of a subject.

14. The container of claim 12, wherein the mucoadhesive is a block copolymer of ethylene oxide and propylene oxide of a formula I:

wherein x is an integer having an average value ranging from about 2 to about 128;

y is an integer having an average value ranging from about 14 to about 80; and

z is an integer having an average value ranging from 2 to about 128.

15. The container of claim 12, wherein the mucoadhesive is poloxamer 407.

16. The container of claim 12, wherein the local anesthetic is lidocaine, tetracaine, bupivacaine, prilocaine, mepivacaine, procaine, chloroprocaine, ropivacaine, dibucaine, etidocaine, benzocaine, a pharmaceutically-acceptable salt thereof, or a mixture thereof.

17. The container of claim 16, wherein the local anesthetic is lidocaine or a pharmaceutically-acceptable salt thereof.

18. The container of claim 12, wherein the opioid is morphine or loperamide or a pharmaceutically-acceptable salt thereof.

19. The container of claim 18, wherein the opioid is morphine or a pharmaceutically-acceptable salt thereof.

20. A method of inducing local anesthesia in a subject comprising topically applying a composition comprising a mucoadhesive, a local anesthetic or a pharmaceutically-acceptable salt thereof, and an opioid or a pharmaceutically-acceptable salt thereof to a subject, wherein the mucoadhesive is a block copolymer of ethylene oxide and propylene oxide.

21. The method of claim 20, wherein the composition is applied to the buccal mucous membrane.

22. The method of claim 20, wherein an amount of the local anesthetic is within a range of from about 0.01 percent to about 0.5 percent of a total weight of the composition.

23. The method of claim 20, wherein an amount of the opioid is within a range of from about 0.05 percent to about 1 percent of a total weight of the composition.

24. The method of claim 20, wherein an amount of the mucoadhesive is within a range of from about 0.1 percent to about 40 percent of a total weight of the composition.

25. The method of claim 24, wherein an amount of the mucoadhesive is within a range of from about 15 percent to about 25 percent of a total weight of the composition.

26. The method of claim 20, wherein the mucoadhesive is a block copolymer of ethylene oxide and propylene oxide of a formula I:

wherein x is an integer having an average value ranging from about 2 to about 128;

y is an integer having an average value ranging from about 14 to about 80; and

z is an integer having an average value ranging from 2 to about 128.

27. The method of claim 20, wherein the mucoadhesive is poloxamer 407.

28. The method of claim 20, wherein the local anesthetic is lidocaine, tetracaine, bupivacaine, prilocaine, mepivacaine, procaine, chloroprocaine, ropivacaine, dibucaine, etidocaine, benzocaine, a pharmaceutically-acceptable salt thereof, or a mixture thereof.

29. The method of claim 28, wherein the local anesthetic is lidocaine or a pharmaceutically-acceptable salt thereof.

30. The method of claim 20, wherein the opioid is morphine or loperamide or a pharmaceutically-acceptable salt thereof.

31. The method of claim 30, wherein the opioid is morphine or a pharmaceutically-acceptable salt thereof.