Bismuth-thiols as antiseptics for agricultural, industrial and other uses
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Publication Number
US-9408393-B2
Publication Date
2016-08-09
Expiration Date
Abstract
Compositions and methods, including novel homogeneous microparticulate suspensions, are described for treating natural and artificial surfaces that contain bacterial biofilm, including unexpected synergy or enhancing effects between bismuth-thiol (BT) compounds and certain antibiotics, to provide formulations including antiseptic formulations. 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 certain gram-positive bacterial infections, and distinct preferential efficacies of certain such compositions for treating certain gram-negative bacterial infections.
Core Innovation
The invention provides bismuth-thiol (BT) antiseptic compositions and methods for treating or preventing microbial infections. The BT compositions are associated with antibacterial and anti-biofilm effects, including inhibition of cell viability or cell growth of planktonic cells and inhibition of biofilm formation and biofilm viability or biofilm growth of biofilm-form cells.
The document further emphasizes unexpected synergy, enhancement, or supra-additive behavior when BT microparticles are combined with selected antibiotics. Fractional inhibitory concentration index (FICI) and fractional bactericidal concentration index (FBCI) concepts are used to describe antibiotic-BT interactions.
In addition, the document describes BT compositions that form a substantially monodisperse suspension of BT microparticles with a volumetric mean diameter range, including specific BT compound identities such as BisEDT. The disclosed methods include protecting a plant against a bacterial, fungal or viral pathogen by contacting the plant with an effective amount of the BT composition under conditions and for a time sufficient to prevent infection and/or inhibit planktonic and biofilm cells.
Claims Coverage
Independent claim clm-00001 is identified. The independent claim contains two core inventive elements: use of a BT composition containing BT microparticles in a defined volumetric mean diameter range, and plant protection by contacting to prevent infection and to inhibit planktonic and biofilm viability/growth and biofilm formation of the pathogen.
Plant protection using BT microparticle suspension
A method for protecting a plant against a bacterial, fungal or viral pathogen by contacting the plant with an effective amount of a bismuth-thiol (BT) composition under conditions and for a time sufficient for prevention of infection and/or inhibition of cell viability or cell growth of substantially all planktonic cells, inhibition of biofilm formation, and inhibition of biofilm viability or biofilm growth of substantially all biofilm-form cells.
Substantially monodisperse BT microparticles of defined size
The BT composition comprises a substantially monodisperse suspension of microparticles that comprise a BT compound, the microparticles having a volumetric mean diameter of from about 0.4 µm to about 10 µm.
Across the identified independent claim, the claim coverage centers on plant protection using a BT antiseptic composition formulated as a substantially monodisperse suspension of BT microparticles within a specified volumetric mean diameter range, combined with effects directed to infection prevention, planktonic cell viability/growth inhibition, and biofilm formation and biofilm cell viability/growth inhibition.
Stated Advantages
Prevention of infection of the plant by the bacterial, fungal or viral pathogen.
Inhibition of cell viability or cell growth of substantially all planktonic cells of the pathogen.
Inhibition of biofilm formation by the pathogen.
Inhibition of biofilm viability or biofilm growth of substantially all biofilm-form cells of the pathogen.
Synergizing or enhancing antimicrobial efficacy when the BT composition is combined with a synergizing or enhancing antibiotic.
Documented Applications
Treatment and assessment contexts described in the disclosure include enhanced healing indicators in scratch-wounded cell monolayers exposed to bacterial biofilms and synergy with antibiotics against multiple bacterial species/strains, including antibiotic-resistant organisms.
A rat graft infection model is described, where BT plus antibiotics and/or implant impregnation reduces resistant Staphylococcus epidermidis biofilm load.
Biofouling-related activity is described, including marine bacteria MICs and barnacle/algae settlement inhibition.
Protecting a plant against a bacterial, fungal or viral pathogen by contacting the plant with a BT composition.
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