Bismuth-thiol compositions and methods of use
Inventors
Baker, Brett Hugh James • MILLARD, Jeffrey W.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11464749-B2
Publication Date
2022-10-11
Expiration Date
Abstract
The invention relates to Bis-thiol compounds and pharmaceutical preparations thereof. The invention further relates to methods of treating, managing or lessening the severity of pulmonary infections in a subject, the method comprising administering to the subject a bismuth-thiol (BT) composition that comprises at least one BT compound.
Core Innovation
The invention relates to treating, managing, or lessening the severity of cystic fibrosis (CF) symptoms and infections by administering an aerosol comprising dispersed liquid droplets. The aerosol includes a bismuth-thiol (BT) composition with bismuth-1,2-ethanedithiol (BisEDT) microparticles suspended therein, wherein the BisEDT microparticles have a D90 of less than about 2 µm as measured by laser diffraction, and at least 70% of the liquid droplets have a mass median aerodynamic diameter (MMAD) from about 0.4 µm to about 5 µm as measured by cascade impaction or laser time of flight.
The invention also provides a method for treating, managing, or lessening the severity of symptoms and infections associated with one or more pulmonary diseases or infections by administering the same aerosol comprising dispersed liquid droplets and the BT composition. The disclosed approach emphasizes delivery of the BisEDT microparticle composition via aerosol to the lungs with defined lung deposition and pharmacokinetic constraints, including embodiments that specify deposition of at least 60% or at least 15% of the dose in the lungs and an average half-life of more than 2 days in a lung region.
Dependent embodiments further refine droplet distribution, specify pulmonary infections from enumerated groups, and allow focusing on non-tuberculous Mycobacteria (NTM). Additional embodiments narrow infection targeting through a detailed selectable pathogen list that includes bacterial and fungal organisms, including antimicrobial-resistant strains, while other embodiments refine whether the pulmonary disease or infection is associated with cystic fibrosis.
Claims Coverage
The independent claim coverage includes two independent method claims centered on administering an aerosol of dispersed liquid droplets containing BisEDT microparticles, with defined microparticle size and droplet aerodynamic size distribution. Across the independent claims, two main quantitative inventive constraints are used: BisEDT microparticle D90 (< about 2 µm) and dispersed droplet MMAD distribution (at least 70% within about 0.4 µm to about 5 µm).
Aerosolized BisEDT microparticles for cystic fibrosis symptom and infection management with defined particle and droplet size
Administering to a subject an aerosol comprising a plurality of dispersed liquid droplets, wherein the liquid droplets comprise a bismuth-thiol (BT) composition that comprises bismuth-1,2-ethanedithiol (BisEDT) microparticles suspended therein, wherein the BisEDT microparticles have a D90 of less than about 2 µm as measured by laser diffraction, and wherein at least 70% of the liquid droplets have a mass median aerodynamic diameter (MMAD) from about 0.4 µm to about 5 µm as measured by cascade impaction or laser time of flight.
Aerosolized BisEDT microparticles for pulmonary disease or infection symptom and infection management with defined particle and droplet size
Administering to the subject an aerosol comprising a plurality of dispersed liquid droplets, wherein the liquid droplets comprise a bismuth-thiol (BT) composition that comprises BisEDT microparticles suspended therein, the BisEDT microparticles having a D90 of less than about 2 µm as measured by laser diffraction, and wherein at least 70% of the liquid droplets have a MMAD from about 0.4 µm to about 5 µm as measured by cascade impaction or laser time of flight.
The independent claims are directed to aerosol delivery of a BT composition comprising BisEDT microparticles with a laser-diffraction D90 constraint and an aerodynamic droplet MMAD distribution constraint. Dependent embodiments then further refine lung deposition, BisEDT half-life in a lung region, pathogen scope, and inclusion or exclusion of cystic-fibrosis-associated indications.
Stated Advantages
Treating, managing, or lessening the severity of cystic fibrosis (CF) symptoms and infections.
Treating, managing, or lessening the severity of symptoms and infections associated with one or more pulmonary diseases or infections.
Documented Applications
Aerosol administration of BisEDT microparticle BT composition for treating, managing, or lessening CF symptoms and infections.
Aerosol administration of BisEDT microparticle BT composition for treating, managing, or lessening symptoms and infections associated with one or more pulmonary diseases or infections.
Pulmonary infection indications including bronchiectasis infection, pneumonia, valley fever, allergic bronchopulmonary aspergillosis, ventilator acquired pneumonia, hospital acquired pneumonia, community acquired pneumonia, ventilator associated tracheobronchitis, lower respiratory tract infection, non-tuberculous Mycobacteria (NTM), anthrax, legionellosis, pertussis, bronchitis, Bronchiolitis, chronic obstructive pulmonary disease associated infection, and post-lung transplantation.
Pulmonary infections caused by NTM.
Interested in licensing this patent?