Bismuth-thiols as antiseptics for epithelial tissues, acute and chronic wounds, bacterial biofilms and other indications
Inventors
Baker, Brett Hugh James • Domenico, Philip
Assignees
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Publication Number
US-11564903-B2
Publication Date
2023-01-31
Expiration Date
Abstract
Compositions and methods, including novel homogeneous microparticulate suspensions, are described for treating acute wounds, chronic wounds and/or a wound or epithelial tissue surface that contains bacterial biofilm, including unexpected synergy between bismuth-thiol (BT) compounds and certain antibiotics, to provide topical formulations including antiseptic formulations, for management and promotion of wound healing and in particular infected wounds. Previously unpredicted antibacterial properties and anti-biofilm properties of disclosed BT compounds and BT compound-plus-antibiotic combinations are also described, including preferential efficacies of certain such compositions for treating gram-positive bacterial infections, and distinct preferential efficacies of certain such compositions for treating gram-negative bacterial infections.
Core Innovation
The invention relates to bismuth-thiol (BT) antiseptics formulated as topical treatments for acute and chronic wounds and for bacterial biofilms on epithelial tissue surfaces. The invention provides BT compositions comprising solid microparticles, including microparticles comprising BisEDT, in which the microparticles are defined by volumetric mean diameter (VMD) and distribution constraints. The invention addresses antibacterial and anti-biofilm activity against bacterial pathogens at epithelial tissue surfaces.
The invention provides BT formulations as substantially monodisperse microparticulate suspensions with VMD in a specified range, with dependent embodiments refining the VMD range, at-least thresholds, and distribution characteristics. The document also describes BT compound identities including BisEDT and BisBAL and other Bis-* thiol complexes. The invention is supported by biofilm inhibition and epithelial cell healing related evaluation described in the partial content.
Claims Coverage
The provided claims define one independent BT composition claim centered on BisEDT-containing solid microparticles with a specified VMD range and an at least percentage threshold. Dependent claims refine the inventive concept through tighter VMD and threshold constraints, peak VMD and unimodal distribution, and formulation limitations such as exclusion of liposomes.
BisEDT microparticle BT composition with VMD-defined particle size distribution
A bismuth-thiol (BT) composition comprising a plurality of solid microparticles, wherein at least 80% of the microparticles have a volumetric mean diameter (VMD) of from about 0.4 μm to about 5 μm, said microparticles comprising BisEDT.
Raised VMD meeting fraction within the stated range
The composition wherein at least 85% of the microparticles have a VMD of 0.4 μm to 5 μm.
Narrowed VMD range with at-least threshold
The composition wherein at least 80% of the microparticles have a VMD between 1.0 μm and 3 μm.
Peak VMD constraint around a specific value
The composition wherein the microparticles have a peak VMD of about 1.3 microns.
Unimodal size distribution
The composition wherein the microparticles have a unimodal size distribution.
Liposome exclusion
A composition not including a liposome.
Overall, the claims are centered on a BisEDT BT composition using solid microparticles with VMD-based particle-size distribution requirements, with dependent claims adding tighter VMD windows, higher percentage thresholds, a peak VMD around about 1.3 microns, a unimodal distribution requirement, and exclusion of liposomes.
Stated Advantages
The invention describes unexpected synergy when selected BT compounds are combined with specific antibiotics.
The invention describes differential preferential efficacy for gram-positive versus gram-negative pathogens.
The invention reports synergy observations for drug-resistant pathogens such as MRSA and MRSE and for gram-negative organisms such as Pseudomonas aeruginosa and Escherichia coli.
The invention addresses antibacterial and anti-biofilm activity against bacterial pathogens at epithelial tissue surfaces.
Documented Applications
Topical treatment of acute wounds.
Topical treatment of chronic wounds.
Treatment of bacterial biofilm infections on epithelial tissue surfaces.
Topical wound-healing and anti-biofilm formulations.
Biofilm inhibition and biofilm suppression contexts using colony and drip-flow biofilm models.
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