Two-stage transmucosal medicine delivery system for symptom relief

• US 6,893,654 B2
• Filed: 03/18/2002
• Issued: 05/17/2005
• Est. Priority Date: 09/03/1998
• Status: Expired due to Fees

• Current Assignee: JSR NTI, LLC
• Original Assignee: Jsr LLC
• Inventors: Gitchell, Joseph, Shiffman, Saul, Cone, Edward J., Henningfield, Jack E., Pinney, John M.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): VANIK, DAVID L
• Application Number:
  US10/098,307
• Publication Number:
  US 20020102304A1
• Time in Patent Office: 1,156 Days
• Field of Search: 424/435, 424/48, 424/440, 424/434, 424/449, 424/464, 424/451, 424/489, 424/484
• US Class Current: 424/434
• 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 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, said nicotine maintenance compound is 1 to 4 milligrams of encapsulated nicotine salt,

wherein the product is in lozenge form.

2. The two-stage nicotine delivering product of claim 1, wherein said nicotine loading compound is 0.2 to 0.7 milligrams of a nicotine salt.

3. The two-stage nicotine delivering product of claim 2, wherein said nicotine salt is nicotine tartrate.

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

5. The two-stage nicotine delivering product of claim 4, wherein said nicotine is nicotine polacrilex.

6. The two-stage nicotine delivering product of claim 1, 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.

7. The two-stage nicotine delivering product of claim 6, wherein said loaded nicotine concentration is at least 2 nanograms of nicotine per milliliter of blood.

8. The two-stage nicotine delivering product of claim 7, wherein said prolonged concentration of nicotine is at least 10 nanograms of nicotine per milliliter of blood.

9. The two-stage nicotine delivering product of claim 8, 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.

10. The two-stage nicotine delivering product of claim 8, 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.

11. The two-stage nicotine delivering product of claim 1, 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.

12. The two-stage nicotine delivering product of claim 11, 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.

13. 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 counteract said craving within 5 minutes after the base material is orally retained;

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; and

forming the mixture of the base material and the loading and maintenance compounds into a lozenge suitable for being retained in the mouth and thereafter orally manipulated.

14. The method of claim 13, 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.

15. The method of claim 14, 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.

16. The method of claim 13, wherein said base material is a gum base.

17. The method of claim 13, wherein said craving is a nicotine craving and said loading compound is 0.2 to 0.7 milligrams of nicotine salt.

18. The method of claim 13, wherein said craving is a nicotine craving and said maintenance compound is 1 to 4 grams of nicotine.

19. The method of claim 18, wherein said 1 to 4 grams of nicotine is nicotine polacrilex.

20. The method of claim 13, wherein said craving is a nicotine craving and said maintenance compound is encapsulated nicotine salt.

21. A two-stage active agent delivery system that reduces cravings, comprising:

an orally manipulatable base material;

a buffer dispersed within said base material; and

an active ingredient intermixed with said base material and said buffer, said active ingredient cooperating with said buffer upon oral manipulation of the base material for therewith causing release of an initial dose of an active agent achieving a rapid transmucosally absorbable pharmacological effect reducing a craving and releasing a second dose of the active agent achieving a prolonged transmucosally absorbable pharmacological effect reducing the craving, said active ingredient is nicotine, said nicotine is selected from the group consisting of nicotine salts and nicotine polacrilex, and the nicotine is of at least two forms,

wherein the system is in the form of a lozenge.

22. The system of claim 21, wherein said buffer is present in sufficient amount to elevate the pH in a user'"'"'s mouth to between about 7.5 and 9.5.

23. The system of claim 21, wherein said buffer is present in sufficient amount to elevate the pH in a user'"'"'s mouth for at least 15 minutes.

24. The system of claim 21, wherein the buffer is selected from the group consisting of bicarbonate and carbonate buffers.

25. The system of claim 21, wherein said buffer is a sodium free buffer.

26. The system of claim 21, wherein said buffer is selected from the group consisting of calcium carbonate, potassium citrate, and dipotassium phosphate.

27. The system of claim 21, wherein there is about 30 to 70 milligrams of buffer dispersed throughout said base material.

28. The system of claim 21, wherein the initial dose releases from about 0.2 to about 0.7 milligrams of nicotine within about 5 minutes.

29. The system of claim 28, wherein the initial dose achieves a concentration of about 2 nanograms of nicotine per milliliter of blood.

30. The system of claim 29, wherein the second dose achieves a concentration of about 10 nanograms of nicotine per milliliter of blood.

31. The system of claim 28, wherein the second dose achieves a concentration in the blood of the active ingredient exceeding the concentration achieved by the initial dose.

32. The system of claim 31, wherein the second dose concentration is maintained for at least about 20 minutes.