# US 10,441,537 B2 · Unit doses, aerosols, kits, and methods for treating heart conditions by pulmonary administration > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,441,537 B2 - Document ID: US10441537B2 - Status: Granted - Kind: B2 - Application number: 15/976,516 - Filed: 2018-05-10 - Published: 2018-11-15 - Granted: 2019-10-15 - Earliest claimed: 2017-05-10 - Assignees: InCarda Therapeutics, Inc. - Applicants: InCarda Therapeutics, Inc. - Inventors: Carlos Schuler; Rangachari Narasimhan; Luiz Belardinelli; Prashanti Madhavapeddi - Web page: https://patentgrep.com/patent/US10441537B2 ## CPC - A61K 9/0078: {for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions} - A61K 9/008: {comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]} - A61K 31/435: having six-membered rings with one nitrogen as the only ring hetero atom - A61K 31/7076: containing purines, e.g. adenosine, adenylic acid - A61P 9/06: Antiarrhythmics - A61M 15/00: Inhalators {(drug delivery in endotracheal tubes A61M16/04)} - 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 - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} ## Abstract Methods of treating a heart condition include administering by inhalation an effective amount of at least one antiarrhythmic pharmaceutical agent to a patient in need thereof. Nebulized drug product and kits are also contemplated. ## Claims ### Claim 1 An inhalation pharmaceutical composition comprising a unit dose of an antiarrhythmic agent in a liquid solution that is therapeutically effective for treating atrial arrhythmia in a human subject in need thereof, wherein said antiarrhythmic agent is selected from the group consisting of: flecainide, a salt thereof, and a solvate thereof, wherein said unit dose of said antiarrhythmic agent is about 50 mg to about 350 mg, wherein a concentration of said antiarrhythmic agent in said unit dose is about 35 to about 60 mg/mL, and wherein said pharmaceutical composition is formulated for administration via inhalation. ### Claim 2 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein said unit dose of said antiarrhythmic agent, when administered to a healthy subject via inhalation, has a maximum ΔQRS of from about 1 to about 100 msec as measured by electrocardiography in a human pharmacokinetics/pharmacodynamics study. ### Claim 3 (depends on 2) The inhalation pharmaceutical composition of claim 2, wherein said maximum ΔQRS is from about 3 to about 20 msec. ### Claim 4 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein said unit dose of said antiarrhythmic agent, when administered to a healthy subject via inhalation, has a maximum ΔQRS same as or greater than a maximum ΔQRS achieved by a second amount of said antiarrhythmic agent when administered intravenously to said subject as measured by electrocardiography in a human pharmacokinetics/pharmacodynamics study, wherein said unit dose is less than half of said second amount. ### Claim 5 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein said concentration of said antiarrhythmic agent is about 35 to about 50 mg/mL. ### Claim 6 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein said concentration of said antiarrhythmic agent is about 45 mg/mL. ### Claim 7 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein said concentration of said antiarrhythmic agent is 45 mg/mL. ### Claim 8 (depends on 1) The inhalation pharmaceutical composition of claim 1, comprising about 60 to about 130 mg of said antiarrhythmic agent. ### Claim 9 (depends on 1) The inhalation pharmaceutical composition of claim 1, comprising about 50 to about 90 mg of said antiarrhythmic agent. ### Claim 10 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein a volume of said liquid solution in said unit dose is about 1 mL to about 6 mL. ### Claim 11 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein said antiarrhythmic agent comprises flecainide acetate. ### Claim 12 (depends on 1) The inhalation pharmaceutical composition of claim 1, further comprising a pH buffer prepared from acetic acid. ### Claim 13 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein a pH of said inhalation pharmaceutical composition is from 5.0 to 6.5. ### Claim 14 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein said inhalation pharmaceutical composition has physiological isotonicity. ### Claim 15 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein said unit dose of said antiarrhythmic agent, when administered to a healthy subject via inhalation, has a Tmax of from about 0.2 to about 5 minutes as measured in a human pharmacokinetics/pharmacodynamics study. ### Claim 16 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein said unit dose of said antiarrhythmic agent, when administered to a healthy subject via inhalation, has a Cmax of from about 100 to about 250 ng/mL as measured in a human pharmacokinetics/pharmacodynamics study. ### Claim 17 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein said unit dose of said antiarrhythmic agent, when administered to a healthy subject via inhalation, has a AUCLast of from about 100 to about 10000 hr*ng/mL as measured in a human pharmacokinetics/pharmacodynamics study. ### Claim 18 (depends on 17) The inhalation pharmaceutical composition of claim 17, wherein said AUCLast is from about 200 to about 2000 hr*ng/mL. ### Claim 19 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein said unit dose of said antiarrhythmic agent, when administered to a healthy subject via inhalation, has a distribution t1/2 of from about 0.1 to about 15 minutes as measured in a human pharmacokinetics/pharmacodynamics study. ### Claim 20 (depends on 19) The inhalation pharmaceutical composition of claim 19, wherein said distribution t1/2 is from about 3 to about 5 minutes. ### Claim 21 (depends on 1) The inhalation pharmaceutical composition of claim 1, wherein said unit dose of said antiarrhythmic agent, when administered to a healthy subject via inhalation, has an elimination tin, of from about 1 to about 25 hours as measured in a human pharmacokinetics/pharmacodynamics study. ### Claim 22 (depends on 21) The inhalation pharmaceutical composition of claim 21, wherein said elimination t1/2 is from about 8.5 to about 10.5 hours. ### Claim 23 (depends on 1) A kit comprising the inhalation pharmaceutical composition of claim 1 and an aerosolization device.