Nicotine-containing pharmaceutical compositions

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 α 7 or α 4 β 2 . The composition is useful for treatment of central nervous system conditions, diseases and disorders, and as a nicotine replacement therapy.

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 4 β 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 4 β 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 4 β 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 4 β 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.