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-12186283-B2
Publication Date
2025-01-07
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 concerns bismuth-thiol (BT) compositions, including bismuth-1,2-ethanedithiol (BisEDT), formulated for pulmonary use. The disclosed compositions are administered as an aerosol comprising dispersed liquid droplets in a gas or as a pharmaceutical composition comprising BT with BisEDT suspended therein.
A central aspect is the selection of BT particle size within the BT composition and the dispersed droplet size distribution to support deep lung delivery. The aerosol includes a plurality of dispersed liquid droplets in a gas in which BisEDT particles are suspended, and embodiments specify BisEDT particle D90 limits together with dispersed liquid droplets having a mass median aerodynamic diameter (MMAD) within about 0.4 to about 5.
The disclosed approaches are directed to treating or controlling pulmonary infections, with particular emphasis on cystic fibrosis (CF). The document describes treatment goals that include reducing biofilm formation and/or viability, reducing sputum viscosity, and reducing pathogen load and/or exotoxin effects, including coverage of CF and non-CF pulmonary pathogens and resistant strains.
The document further describes additional characterization and performance features tied to deep lung retention. It includes embodiments that specify lung residence time/half-life metrics after deposition in the deep lung region, including average half-life of more than 2 days, and optional combination therapy with antibiotics and/or CFTR modulators and/or bronchodilators.
Claims Coverage
The partial content provides two independent claims. The inventive features center on BT (BisEDT)-containing formulations in which BisEDT particle size (D90 via laser diffraction) is tightly constrained, and for the aerosol also by specifying that most droplets fall within a target MMAD range for deep lung delivery.
Aerosol with suspended BisEDT particles and constrained droplet MMAD distribution
An aerosol comprising a plurality of dispersed liquid droplets in a gas, wherein the liquid droplets comprise a bismuth-thiol (BT) composition comprising bismuth-1,2-ethanedithiol (BisEDT) suspended therein, with BisEDT particles having a D90 of less than about 2 as measured by laser diffraction, and wherein at least 70% of the total number of dispersed liquid droplets have an MMAD from about 0.4 to about 5 as measured by cascade impaction or laser time of flight.
Pharmaceutical composition with suspended BisEDT particles having a D90 upper limit
A pharmaceutical composition comprising a BT composition that comprises BisEDT suspended therein, wherein the BT composition comprises a plurality of BisEDT particles having a D90 of less than or equal to 1.9 as measured by laser diffraction.
Across the independent claims, the core coverage is provided by BT (BisEDT)-containing formulations in which BisEDT particle size (D90 via laser diffraction) is tightly constrained, and for the aerosol also by specifying that most droplets fall within a target MMAD range for deep lung delivery. The partial content also indicates dependent refinements that tighten particle size metrics and, for the pharmaceutical composition, can exclude liposomes.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating or controlling pulmonary infections, especially cystic fibrosis (CF), using inhaled or topical BT compositions.
Reducing biofilm formation and/or viability in pulmonary infections.
Reducing sputum viscosity in cystic fibrosis contexts.
Reducing pathogen load and/or exotoxin effects in pulmonary infections.
Providing coverage across CF and non-CF pulmonary pathogens, including resistant strains.
Interested in licensing this patent?