Composition for nasal administration

• US 5,629,011 A
• Filed: 07/12/1994
• Issued: 05/13/1997
• Est. Priority Date: 02/05/1992
• Status: Expired due to Term

• Current Assignee: Archimedes Development Limited (Kirin Holdings Company Limited)
• Original Assignee: Danbiosyst UK Ltd (Kirin Holdings Company Limited)
• Inventors: Illum, Lisbeth
• Primary Examiner(s): VENKAT, JYOTHSNA A
• Application Number:
  US08/256,431
• Time in Patent Office: 1,036 Days
• Field of Search: 424/434, 424/489, 424/499
• US Class Current: 424/434
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0043 Nose

Abstract

A composition for nasal administration of polar metabolites of opioid analgesics comprises a polar metabolite of an opioid analgesic and an absorption promoting agent. Preferred metabolites morphine-6-glucuronide and morphine-6-sulphate. A preferred absorption promoting agent is chitosan but other suitable agents include cationic polymers, bioadhesive agents, surface active agents, fatty acids, chelating agents, mucolytic agents, cyclodextrin, microsphere preparations or combinations thereof.

Claims

1. A composition for nasal administration comprising a polar metabolite of an opioid analgesic selected from the group consisting of glucuronides and ethereal sulphates of an opioid analgesic, wherein the opioid analgesic is selected from the group consisting of morphine, codeinc, levorphanol, hydromorphone, oxymorphone, nalbuphine, buprenophine, nalorphine, hydrocodone, oxycodone and butorphanol, and an effective amount of an absorption promoting agent to allow nasal absorption of a pharmacologically effective amount of the metabolite after nasal administration of the composition;

wherein the absorption promoting agent is selected from the group consisting of a cationic polymer, a surface active agent, a chelating agent, a mucolytic agent, a cyclodextrin, and combinations thereof.

2. A composition according to claim 1 wherein the metabolite is a glucuronide.

3. A composition according to claim 1 wherein the metabolite is an ethereal sulphate of an opioid analgesic.

6. The composition of claim 1 wherein the absorption promoting agent is a cationic polymer and wherein the cationic polymer is chitosan.

7. A composition according to claim 1 wherein the composition comprises a solution or dispersion of the absorption promoting agent.

8. A composition according to claim 1 wherein the composition comprises microspheres which are formed of an absorption promoting agent.

15. The composition of claim 1 wherein the polar metabolite is a morphine metabolite.

16. The composition of claim 1 wherein the absorption promoting agent is a surface active agent selected from the group consisting of a phospholipid and a lysophospholipid.

19. The method of claim 1 wherein the absorption promoting agent is a cationic polymer and wherein the cationic polymer is chitosan.

21. The composition of claim 1 wherein the absorption promoting agent is a surface active agent present in an amount between 0.02 and 10%.

4. A composition for nasal administration comprising morphine-6-glucuronide and an effective amount of an absorption promoting agent to allow nasal absorption of the morphine-6-glucuronide after nasal administration of the composition, wherein the absorption promoting agent is selected from the group consisting of a cationic polymer, a surface active agent, a chelating agent, a mucolytic agent, a cyclodextrin,and combinations thereof.

5. A composition for nasal administration comprising morphine-6-sulphate and an effective amount of an absorption promoting agent to allow nasal absorption of the morphine-6-sulphate after nasal administration of the composition, wherein the absorption promoting agent is selected from the group consisting of a cationic polymer, a surface active agent, a chelating agent, a mucolytic agent, a cyclodextrin, and combinations thereof.

9. A method of delivery of a polar metabolite of an opioid analgesic comprising administering a composition for nasal administration to the nasal mucosa wherein the composition comprises a polar metabolite of an opioid analgesic selected from the group consisting of glucuronide and ethereal sulphates of an opioid analgesic, wherein the opioid analgesic is selected from the group consisting of morphine, codeine, levorphanol, hydromorphone, oxymorphone, nalbuphine, buprenorphine, nalorphine, hydrocodone, oxycodone and butorphanol, and an effective amount of an absorption promoting agent selected from the group consisting of a cationic polymer, a surface active agent, a chelating agent, a mucolytic agent, a cyclodextrin, and combinations thereof to allow nasal absorption of a pharmacologically effective amount of the metabolite.

13. The method of claim 9 wherein the composition comprises a solution or dispersion of the absorption promoting agent.

14. The method of claim 9 wherein the composition comprises microspheres which are formed of an absorption promoting agent.

17. The method of claim 9 wherein the opioid analgesic is morphine.

18. The method of claim 9 wherein the absorption promoting agent is a surface active agent selected from the group consisting of a phospholipid and a lysophospholipid.

20. The method of claim 9 comprising nasally administering the composition in a pharmacologically effective amount for the alleviation of pain.

22. The method of claim 9 wherein the absorption promoting agent is a surface active agent present in an amount between 0.02 and 10%.

10. A method of delivery of morphine-6-glucuronide comprising administering morphine-6-glucuronide and an effective amount of an absorption promoting agent to allow nasal absorption of the morphine-6-glucuronide after nasal administration of the composition, wherein the absorption promoting agent is selected from the group consisting of a cationic polymer, a surface active agent, a chelating agent, a mucolytic agent, a cyclodextrin, and combinations thereof.

11. A method of delivery of morphine-6-sulphate comprising administering a composition for nasal administration to the nasal mucosa wherein the composition comprises morphine-6-sulphate and an effective amount of an absorption promoting agent selected from the group consisting of a cationic polymer, a surface active agent, a chelating agent, a mucolytic agent, a cyclodextrin, and combinations thereof to allow nasal absorption of a pharmacologically effective amount of the morphine-6-sulphate.

12. The method of claim 11 wherein the absorption promoting agent is a cationic polymer which is chitosan, and wherein the chitosan is in the form of microspheres.