# US 9,040,591 B2 · Methods and compositions comprising at least one α3 βA4 nAChR antagonist or pharmaceutically acceptable salt thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,040,591 B2 - Document ID: US9040591B2 - Status: Granted - Kind: B2 - Application number: 13/553,453 - Filed: 2012-07-19 - Published: 2013-01-31 - Granted: 2015-05-26 - Earliest claimed: 2003-03-14 - Assignees: AGI Therapeutics Public Limited Company - Applicants: John Devane - Inventors: John Devane - Web page: https://patentgrep.com/patent/US9040591B2 ## CPC - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 31/13: Amines {(A61K31/04 takes precedence)} - A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)} - A61K 31/14: Quaternary ammonium compounds, e.g. edrophonium, choline (betaines A61K31/205) - A61K 31/225: Polycarboxylic acids - A61K 31/34: having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide - A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil - A61K 31/415: 1,2-Diazoles - A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof - A61K 31/445: Non condensed piperidines, e.g. piperocaine - A61K 31/47: Quinolines; Isoquinolines - A61K 31/4965: Non-condensed pyrazines - A61K 31/497: containing further heterocyclic rings - A61K 31/56: Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids - A61K 31/727: Heparin; Heparan - A61K 33/24: Heavy metals; Compounds thereof - A61K 35/60: Fish, e.g. seahorses; Fish eggs - A61K 38/13: Cyclosporins - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 1/12: Antidiarrhoeals - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 13/00: Drugs for disorders of the urinary system - A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps - A61P 27/02: Ophthalmic agents - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention is directed to methods and formulations for treating, modifying, and/or managing gastrointestinal secretion, and intestinal conditions that cause the same. Methods of using at least one α3 β4 nAChR antagonist and formulations comprising at least one α3 β4 nAChR antagonist, or pharmaceutically acceptable salt thereof, are included. ## Claims ### Claim 1 A pharmaceutical composition comprising a therapeutically-effective amount of N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine or pharmaceutically-acceptable salt thereof and at least one pharmaceutically-acceptable excipient in a modified-release formulation in a dosage form chosen from oral, intra-nasal, and transdermal forms; wherein: N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine exhibits an IC50 value for the α3 β4 sub-type of nAChR ranging from 1.0=10-6 to 1×10-9 M or exhibits a potency for the α3 β4 nAChR sub-type at least two-times greater in comparison to at least one other nAChR sub-type; the composition produces a peak:trough plasma level ratio of greater than zero to less than about 4:1; the therapeutically-effective amount ranges from about 2 mg to about 12 mg per day; the composition minimizes at least one side effect chosen from effects on heart rate, blood pressure, vision, and bladder function associated with a conventional formulation of the at least one an α3 β4 nAChR antagonist or pharmaceutically-acceptable salt thereof; and N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine or the pharmaceutically-acceptable salt thereof is the sole active pharmaceutical compound in the composition. ### Claim 2 (depends on 1) The composition according to claim 1, wherein the N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine comprises racemic N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine, enriched (R)—N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine, enriched (S)—N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine, substantially pure (R)—N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine, substantially pure (S)—N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine, or pharmaceutically-acceptable salts of any of the foregoing. ### Claim 3 (depends on 2) The composition according to claim 2, wherein the N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine comprises racemic N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine, or a pharmaceutically-acceptable salt thereof. ### Claim 4 (depends on 2) The composition according to claim 2, wherein the N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine comprises enriched (S)—N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine, enriched (R)—N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine, or pharmaceutically-acceptable salts thereof. ### Claim 5 (depends on 2) The composition according to claim 2, wherein the N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine comprises substantially pure (S)—N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine, substantially pure (R)—N-2,3,3-tetramethylbicyclo-[2.2.1]heptan-2-amine, or pharmaceutically acceptable salts thereof. ### Claim 6 (depends on 1) The composition according to claim 1, wherein the composition further comprises at least one immediate-release component. ### Claim 7 (depends on 1) The composition according to claim 1, wherein the composition comprises extended-release components, or delayed-release components, or both extended-release and delayed-release components. ### Claim 8 (depends on 1) The composition according to claim 1, wherein the composition is chosen from a matrix formulation, an osmotic pump-based formulation, and a modified-membrane formulation. ### Claim 9 (depends on 1) The composition according to claim 1, wherein the composition, when tested in a U.S. Pharmacopeia (USP) Type 2 Apparatus, at 37° C., stirred at 50 rpm, and in pH 6.8 phosphate buffer, releases less than about 60% of the at least one antagonist in less than about 2 hours; greater than or equal to about 40% in about 12 or more hours; and about 70% or more in about 24 or more hours. ### Claim 10 (depends on 9) The composition according to claim 9, wherein the composition releases less than or equal to about 60% of the at least one antagonist in about 2 hours, less than or equal to about 70% in about 4 hours; greater than or equal to about 50% in about 8 hours; greater than or equal to about 65% in about 12 hours; and greater than or equal to about 80% in about 24 hours. ### Claim 11 (depends on 10) The composition according to claim 10, wherein the composition releases less than or equal to about 50% of the at least one antagonist in about 2 hours, less than or equal to about 65% in about 4 hours; greater than or equal to about 60% in about 8 hours; greater than or equal to about 70% in about 12 hours; and greater than or equal to about 80% in about 24 hours. ### Claim 12 (depends on 11) The composition according to claim 11, wherein the composition releases less than or equal to about 40% of the at least one antagonist in about 2 hours, from about 20% to about 60% in about 4 hours; greater than or equal to about 70% in about 8 hours; greater than or equal to about 75% in about 12 hours; and greater than or equal to about 80% in about 24 hours.