Two-stage transmucosal medicine delivery system for symptom relief

• US 20020102304A1
• Filed: 03/18/2002
• Published: 08/01/2002
• Est. Priority Date: 09/03/1998
• Status: Active Grant

• Current Assignee: JSR NTI, LLC
• Original Assignee: Edward J. Cone, Jack E. Henningfield, John M. Pinney, Joseph Gitchell, Saul Shiffman
• Inventors: Shiffman, Saul, Cone, Edward J., Gitchell, Joseph, Henningfield, Jack E., Pinney, John M.
• Granted Patent: US 6,893,654 B2
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 9/0058 Chewing gums non-medicinal aspects, preparing chewing gum A23G4/00; chewing gum for care of the teeth or oral cavity, e.g. with breath freshener A61Q11/00
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules

Abstract

A two-stage medicine delivery system provides an initial dose of medicine and a second dose of medicine. The initial and second doses are capable of achieving a rapid pharmacological effect and a prolonged pharmacological effect, respectively. The two-stage medicine delivery system preferably delivers a craving reduction substance, in which case, the rapid and prolonged pharmacological effects include a rapid and prolonged craving reduction. Preferably, the delivery system is a nicotine delivery system which is provided in chewing gum form or lozenge form and which provides the nicotine in a transmucosally absorbable form. The two-stage medicine delivery system preferably releases a buffering agent which increases a pH level in a user'"'"'s mouth to facilitate absorption of the medicine when the delivery system is placed in the user'"'"'s mouth. A method of making the medicine delivery system also is provided. The system and apparatus can be adapted to reduce cravings for alcohol, food, drugs (e.g., cocaine, opiates and the like) and tobacco products, especially tobacco products containing nicotine.

Claims

1. A two-stage medicine delivery system comprising:

means for providing an initial dose of medicine capable of achieving a rapid pharmacological effect; and

means for providing a second dose of medicine capable of achieving a prolonged pharmacological effect.

2. The two-stage medicine delivery system of claim 1, wherein said system is in chewing gum form.

3. The two-stage medicine delivery system of claim 2, wherein the medicine is nicotine.

4. The two-stage medicine delivery system of claim 1, wherein said system is in lozenge form.

5. The two-stage medicine delivery system of claim 1, wherein the medicine is nicotine.

6. The two-stage medicine delivery system of claim 1, wherein said means for providing an initial dose and said means for providing a second dose are adapted to provide transmucosal absorption of said initial and second doses when said means for providing an initial dose and said means for providing a second dose are placed in a user'"'"'s mouth.

7. The two-stage medicine delivery system of claim 6, wherein said medicine is nicotine.

8. The two-stage medicine delivery system of claim 7, wherein said mea ns for providing an initial dose is adapted to release between 0.2 and 0.7 milligrams of nicotine within 5 minutes of having been placed in the user'"'"'s mouth.

9. The two-stage medicine delivery system of claim 8, wherein said means for providing a second dose is adapted to maintain, for at least 20 minutes after said means for providing a second dose has been inserted into the user'"'"'s mouth, a prolonged concentration of nicotine in the user'"'"'s blood which is at least as high as a loaded nicotine concentration achieved in the user'"'"'s blood by said initial dose.

10. The two-stage medicine delivery system of claim 9, wherein said loaded nicotine concentration is at least 2 nanograms of nicotine per milliliter of blood.

11. The two-stage medicine delivery system of claim 10, wherein said prolonged concentration of nicotine is at least 10 nanograms of nicotine per milliliter of blood.

12. The two-stage medicine delivery system of claim 11, further comprising means for releasing a buffering agent which increases a pH level in the user'"'"'s mouth to facilitate transmucosal absorption of said nicotine.

13. The two-stage medicine delivery system of claim 1, further comprising means for releasing a buffering agent which increases a pH level in a user'"'"'s mouth to facilitate absorption of said medicine when said two-stage medicine delivery system is placed in the user'"'"'s mouth.

14. The two-stage medicine delivery system of claim 13, wherein said medicine is nicotine.

15. The two-stage medicine delivery system of claim 14, wherein:

said buffering agent is adapted to elevate the pH level in the user'"'"'s mouth to between about 7.5 and 9.5 within 5 minutes of having been placed in the user'"'"'s mouth;

said means for providing an initial dose is adapted to achieve a loaded nicotine concentration in the user'"'"'s blood between 2 nanograms of nicotine per milliliter of blood and 7 nanograms of nicotine per milliliter of blood, within 5 minutes of having been placed in the user'"'"'s mouth; and

said means for providing a second dose is adapted to increase the concentration of nicotine in the user'"'"'s blood beyond the loaded nicotine concentration to achieve a prolonged concentration of nicotine in the user'"'"'s blood of at least 10 nanograms of nicotine per milliliter of blood, and is further adapted to maintain said prolonged concentration of nicotine for at least 20 minutes.

16. The two-stage medicine delivery system of claim 1, wherein said medicine is a craving counteracting substance, and said rapid and prolonged therapeutic effects include a rapid and prolonged reduction of a craving.

18. The two-stage nicotine delivering product of claim 17, wherein said nicotine loading compound is 0.2 to 0.7 milligrams of a nicotine salt.

19. The two-stage nicotine delivering product of claim 18, wherein said nicotine salt is nicotine tartrate.

20. The two-stage nicotine delivering product of claim 17, wherein said nicotine maintenance compound is 1 to 4 milligrams of nicotine in an ion exchange resin gum.

21. The two-stage nicotine delivering product of claim 20, wherein said nicotine in an ion exchange resin gum is nicotine polacrilex.

22. The two-stage nicotine delivering product of claim 17, wherein said nicotine maintenance compound is 1 to 4 milligrams of encapsulated nicotine salt.

23. The two-stage nicotine delivering product of claim 17, wherein said nicotine maintenance compound is adapted to maintain, for said at least 20 minutes, a prolonged concentration of nicotine in the user'"'"'s blood which is at least as high as a loaded nicotine concentration achieved in the user'"'"'s blood by said nicotine loading compound.

24. The two-stage nicotine delivering product of claim 23, wherein said loaded nicotine concentration is at least 2 nanograms of nicotine per milliliter of blood.

25. The two-stage nicotine delivering product of claim 24, wherein said prolonged concentration of nicotine is at least 10 nanograms of nicotine per milliliter of blood.

26. The two-stage nicotine delivering product of claim 25, further comprising a buffering agent mixed with the base, for raising a pH level in the user'"'"'s mouth to facilitate transmucosal absorption of the nicotine loading compound and the nicotine maintenance compound.

27. The two-stage nicotine delivering product of claim 25, further comprising 30-70 milligrams of a buffering agent mixed with the base, for raising a pH level in the user'"'"'s mouth to between about 7.5 and 9.5 within 5 minutes of when oral actuation begins, to facilitate transmucosal absorption of the nicotine loading compound and the nicotine maintenance compound.

28. The two-stage nicotine delivering product of claim 17, further comprising a buffering agent mixed with the base, for raising a pH level in the user'"'"'s mouth to facilitate transmucosal absorption of the nicotine loading compound and the nicotine maintenance compound.

29. The two-stage nicotine delivering product of claim 28, wherein:

said buffering agent is adapted to elevate the pH level in the user'"'"'s mouth to between about 7.5 and 9.5 within 5 minutes of when oral actuation begins;

said nicotine loading compound is adapted to achieve a nicotine loaded concentration in the user'"'"'s blood between 2 nanograms of nicotine per milliliter of blood and 7 nanograms of nicotine per milliliter of blood, within 5 minutes of when oral actuation begins; and

said nicotine maintenance compound is adapted to increase the concentration of nicotine in the user'"'"'s blood beyond the nicotine loaded concentration to achieve a prolonged concentration of nicotine in the user'"'"'s blood of at least 10 nanograms of nicotine per milli-liter of blood, and is further adapted to maintain said prolonged concentration of nicotine for at least 20 minutes.

17. A two-stage nicotine delivering product for use in counteracting cravings for nicotine-containing tobacco products, comprising:

a base;

a nicotine loading compound mixed with the base so that oral actuation of the base causes the nicotine loading compound to be released into a user'"'"'s mouth for transmucosal absorption within the first 5 minutes after oral actuation begins; and

a nicotine maintenance compound mixed with the base so that oral actuation of the base causes the nicotine maintenance compound to be released into the user'"'"'s mouth for prolonged transmucosal absorption which lasts at least 20 minutes beyond said first five minutes.

30. A method of making a medicine delivery system which reduces a craving when orally retained, said method comprising the steps of:

providing a base material which is adapted to be retained in a user'"'"'s mouth;

mixing a loading compound into the base material so that said loading compound remains releasable and rapidly transmucosally absorbable to cotmteract said craving within 5 minutes after the base material is orally retained; and

mixing a maintenance compound into the base material so that said maintenance compound remains releasable and transmucosally absorbable over a prolonged period of time to counteract said craving for at least 20 minutes after oral retention of the base material begins.

31. The method of claim 30, further comprising the step of:

mixing a buffer into the base material so that said buffer remains releasable to elevate a pH level and facilitate transmucosal absorption of said loading and maintenance compounds within the user'"'"'s mouth when the base material is orally retained.

32. The method of claim 31, wherein said buffer is a bicarbonate buffer adapted to elevate said pH level to about 7.5 to 9.5 within 5 minutes after said base material is orally retained.

33. The method of claim 30, wherein said base material is a gum base.

34. The method of claim 30, wherein said craving is a nicotine craving and said loading compound is 0.2 to 0.7 milligrams of nicotine salt.

35. The method of claim 30, wherein said craving is a nicotine craving and said maintenance compound is 1 to 4 grams of nicotine in an ion exchange resin gum.

36. The method of claim 35, wherein said 1 to 4 grams of nicotine in an ion exchange resin gum is nicotine polacrilex.

37. The method of claim 30, wherein said craving is a nicotine craving and said maintenance compound is encapsulated nicotine salt.