NICOTINE-CONTAINING PHARMACEUTICAL COMPOSITIONS

• US 20110274628A1
• Filed: 05/07/2010
• Published: 11/10/2011
• Est. Priority Date: 05/07/2010
• Status: Abandoned Application

• Current Assignee: Niconovum USA, Inc. (British American Tobacco PLC)
• Original Assignee: Niconovum USA, Inc. (British American Tobacco PLC)
• Inventors: Borschke, August J.
• Application Number:
  US12/775,910
• Publication Number:
  US 20110274628A1
• Time in Patent Office: Days
• US Class Current: 424/48
• 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 31/455 Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• 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 9/009 Sachets, pouches characterised by the material or function of the envelope with gastric retention A61K9/0065; sachets which are not administered but function merely as a container are classified according to the content, e.g. sachets comprising powder for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/12 Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/34 Tobacco-abuse
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A composition intended to be employed for therapeutic purposes incorporates nicotine and at least one other nicotinic compound. Representative forms of nicotine can be as a free base (e.g., as a mixture of nicotine and microcrystalline cellulose), as a form of nicotine salt (e.g., as nicotine bitartrate) or as nicotine polacrilex. The other nicotinic compound is a compound that can be considered to bind selectively to certain nicotinic receptor subtypes, and particularly those of the central nervous system. For example, the other nicotinic compound can be a compound that binds selectively to the nicotinic receptor subtypes α₇ or α₄β₂. The composition is useful for treatment of central nervous system conditions, diseases and disorders, and as a nicotine replacement therapy.

Claims

1. A nicotine-containing composition comprising:

a source of nicotine; and

an agonist or pharmaceutically acceptable salt thereof, having selectivity to a receptor selected from the group consisting of an α

₇ nicotinic receptor subtype and an α

₄β

₂ nicotinic receptor subtype;

wherein the composition is in a pharmaceutically acceptable form.

2. The composition of claim 1, wherein the receptor is an α

₇ nicotinic receptor subtype.

3. The composition of claim 2, wherein the agonist is selected from the group consisting of N-[(2S,3S)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3-yl]-1-benzofuran-2-carboxamide, (5aS,8S,10aR)-5a,6,9,10-Tetrahydro,7H,11H-8,10a-methanopyrido[2′

,3′

;

5,6]pyrano[2,3-d]azepine, 1,4-Diazabicyclo[3.2.2]nonane-4-carboxylic acid, 4-bromophenyl ester, 3-[(3E)-3-[(2,4-dimethoxyphenyl)methylidene]-5,6-dihydro-4H-pyridin-2-yl]pyridine, 2-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole, (5S)-spiro[1,3-oxazolidine-5,8′

-1-azabicyclo[2.2.2]octane]-2-one, N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide, 5-morpholin-4-yl-pentanoic acid (4-pyridin-3-yl-phenyl)-amide, EVP-6124, EVP-4473, TC-6987, and MEM3454.

4. The composition of claim 3, wherein the agonist is N-[(2S,3S)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3-yl]-1-benzofuran-2-carboxamide.

5. The composition of claim 1, wherein the receptor is an α

₄β

₂ nicotinic receptor subtype.

6. The composition of claim 5, wherein the agonist is selected from the group consisting of 7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino(2,3-h)(3) benzazepine, (2S,4E)-5-(5-isopropoxypyridin-3-yl)-N-methylpent-4-en-2-amine, [3-(2(S))-azetidinylmethoxy)pyridine]dihydrochloride, (5aS,8S,10aR)-5a,6,9,10-Tetrahydro,7H,11H-8,10a-methanopyrido[2′

,3′

;

5,6]pyrano[2,3-d]azepine, A-969933, S35836-1, S35678-1, 3-(5,6-Dichloro-pyridin-3-yl)-1S,5S-3,6-diazabicyclo[3.2.0]heptanes, AZD1446, and TC-6499.

7. The composition of claim 6, wherein the agonist is selected from the group consisting of 7,8,9,10-tetrahydro- 6,10-methano-6H-pyrazino(2,3-h)(3) benzazepine and (2S,4E)-5-(5-isopropoxypyridin-3-yl)-N-methylpent-4-en-2-amine.

8. The composition of claim 1, wherein the source of nicotine is in the form of a free base, a salt, a complex, or a solvate.

9. The composition of claim 8, wherein the source of nicotine is nicotine polacrilex, nicotine free base, nicotine tartrate or nicotine bitartrate.

10. The composition of claim 1, wherein the composition is in a form adapted for oral ingestion.

11. The composition of claim 10, wherein the pharmaceutically acceptable form is selected from the group consisting of a pill, tablet, lozenge, mini lozenge, capsule, caplet, pouch, gum and spray.

12. The composition of claim 1, wherein the source of nicotine is nicotine polacrilex, nicotine free base, nicotine tartrate or nicotine bitartrate;

wherein the receptor is an α

₇ nicotinic receptor subtype; and

wherein the pharmaceutically acceptable form is a gum, lozenge, pouch or spray.

13. The composition of claim 1, wherein the source of nicotine is nicotine polacrilex, nicotine free base, nicotine tartrate or nicotine bitartrate;

wherein the receptor is an α

₄β

₂ nicotinic receptor subtype; and

wherein the pharmaceutically acceptable form is a gum, lozenge, pouch or spray.

14. A method for treating a condition, disease or disorder responsive to stimulation of nicotinic acetylcholinergic receptors, comprising orally or nasally administering an effective amount of a pharmaceutical composition according to claim 1 to a human subject.

15. The method of claim 14, wherein said administering step comprises administering the pharmaceutical composition to a human subject as a smoking cessation aid.

16. The method of claim 14, wherein the receptor is an α

₇ nicotinic receptor subtype.

17. The method of claim 14, wherein the receptor is an α

₄β

₂ nicotinic receptor subtype.

18. The method of claim 14, wherein the source of nicotine is nicotine polacrilex, nicotine tartrate, or nicotine bitartrate.

19. The method of claim 14, wherein one or both of the source of nicotine and the agonist are sorbed onto a porous particulate carrier.

20. The method of claim 19, wherein the porous particulate carrier comprises microcrystalline cellulose.

21. The method of claim 14, wherein the composition is in a form adapted for oral ingestion.

22. The method of claim 21, wherein the composition is in the form of a gum, lozenge, tablet, spray or a pouch product.