Unit doses, aerosols, kits, and methods for treating heart conditions by pulmonary administration
Inventors
Schuler, Carlos A. • Narasimhan, Rangachari
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10045939-B2
Publication Date
2018-08-14
Expiration Date
Abstract
Methods of treating atrial arrhythmia include administering an effective amount of at least one antiarrhythmic pharmaceutical agent to a patient in need thereof, such that the at least one antiarrhythmic pharmaceutical agent first enters the heart through the pulmonary vein to the left atrium. Other methods of treating atrial arrhythmia include administering by inhalation an effective amount of at least one antiarrhythmic pharmaceutical agent to a patient in need thereof. An amount of the at least one antiarrhythmic pharmaceutical agent may peak in the coronary sinus of the heart at a time ranging from 10 seconds to 30 minutes from initiation of the administering. Unit doses, aerosols, and kits are also contemplated.
Core Innovation
A method of treating atrial arrhythmia is provided by administering an effective amount of at least one antiarrhythmic pharmaceutical agent through a pulmonary tract and to a pulmonary vein using an aerosolization device. The antiarrhythmic pharmaceutical agent is selected from class I, class II, class III, and class IV antiarrhythmics, and the administration is performed as an aerosolization of a liquid pharmaceutical formulation using a nebulizer configured to administer the agent, wherein aerosolization occurs at room temperature.
The method defines a delivery-to-exposure relationship in which the at least one antiarrhythmic pharmaceutical agent level peaks in a coronary sinus of a heart at a time between 30 seconds and 20 minutes from initiation of the administering to the pulmonary vein. The method further provides restoration of sinus rhythm to normal within 30 minutes of initiation of the administering to the pulmonary vein, and defines coronary sinus concentration at 2.5 minutes after initiation and at 30 minutes after initiation, or alternatively by a percentage of a nominal dose reaching the coronary sinus.
The method also specifies dosing and delivery constraints, including a total amount administered over multiple inhalations within 0.1 mg to 200 mg, and provides options for patient self-administration and self-titration in a conversion of atrial arrhythmia to normal sinus rhythm. The method does not comprise administering an adenosine derivative. The described approach is positioned for pulmonary delivery of antiarrhythmic agents for atrial arrhythmia treatment, including atrial fibrillation and paroxysmal atrial fibrillation.
Claims Coverage
The patent includes two independent claims. Across these claims, at least four inventive features are repeated: pulmonary tract administration to a pulmonary vein by aerosolization using a nebulizer, defined coronary sinus exposure timing and concentration, restoration of normal sinus rhythm within a set time, and exclusion of administering an adenosine derivative.
Pulmonary vein aerosol administration with nebulizer and room-temperature aerosolization
Administering to a pulmonary vein through a pulmonary tract and through use of an aerosolization device an effective amount of at least one antiarrhythmic pharmaceutical agent selected from class I, class II, class III, and class IV antiarrhythmics, where the aerosolization device is a nebulizer configured to administer the agent in a liquid pharmaceutical formulation and aerosolization occurs at room temperature.
Coronary sinus peaking within a defined time window
Providing that the at least one antiarrhythmic pharmaceutical agent level peaks in a coronary sinus of a heart of the patient at a time between 30 seconds and 20 minutes from initiation of the administering to the pulmonary vein.
Normal sinus rhythm restored within 30 minutes
Restoring the patient's sinus rhythm to normal within 30 minutes of initiation of the administering to the pulmonary vein for conversion of atrial arrhythmia to normal sinus rhythm.
Coronary sinus exposure criteria at 2.5 minutes and 30 minutes, or nominal dose reaching coronary sinus
Defining coronary sinus concentration at 2.5 minutes after initiation and at 30 minutes after initiation, or alternatively requiring that a percentage of a nominal dose reaches the coronary sinus.
Exclusion of adenosine derivative
The method does not comprise administering an adenosine derivative.
Patient self-administration and self-titration
Wherein the patient self-administers and self-titrates an effective inhaled dose of the at least one antiarrhythmic pharmaceutical agent for conversion of atrial arrhythmia to normal sinus rhythm.
Independent claim coverage centers on aerosolized delivery of class I–IV antiarrhythmics via a pulmonary tract to a pulmonary vein using a nebulizer with room-temperature aerosolization, together with defined coronary sinus peaking, defined coronary sinus exposure criteria, restoration of normal sinus rhythm within 30 minutes, and exclusion of adenosine derivatives. A separate independent claim further requires patient self-administration and self-titration of the inhaled dose.
Stated Advantages
Restores the patient's sinus rhythm to normal within 30 minutes of initiation of administering to the pulmonary vein.
Provides defined timing of antiarrhythmic agent peak in the coronary sinus between 30 seconds and 20 minutes from initiation.
Achieves coronary sinus concentration criteria at 2.5 minutes and 30 minutes, or a percentage of a nominal dose reaching the coronary sinus.
Avoids administering an adenosine derivative.
Documented Applications
Treating atrial arrhythmia by pulmonary tract administration to a pulmonary vein using aerosolization with a nebulizer.
Converting atrial arrhythmia to normal sinus rhythm, including for atrial fibrillation and paroxysmal atrial fibrillation.
Interested in licensing this patent?