Methods comprising a biocidal polyamine
Inventors
Looper, Ryan • Williams, Dustin • Jeyapalina, Sujeevini • Haussener, Travis • Sebahar, Paul R. • Reddy, Hariprasada R. Kanna
Assignees
CURZA GLOBAL LLC • University of Utah • University of Utah Research Foundation Inc
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Publication Number
US-10440955-B2
Publication Date
2019-10-15
Expiration Date
Abstract
Compounds, compositions, and methods comprising a polyamine compound are described, which may be used to kill, disperse, treat, or reduce biofilms, or to inhibit or substantially prevent biofilm formation. In certain aspects, the present invention relates to compounds, compositions, and methods comprising polyamine compounds that have antimicrobial or dispersing activity against a variety of bacterial strains capable of forming biofilms.
Core Innovation
The invention relates to a method for dispersing or killing a biofilm on a subject by administering an anti-biofilm composition to a surface of the subject. The anti-biofilm composition comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of a biocidal polyamine compound, and the administration is topical, oral, transmucosal, vaginal, or rectal so that the biofilm is effectively dispersed or killed.
The biocidal polyamine compound is selected from the group consisting of a defined biocidal polyamine compound and salts thereof, including hydrogen halide salt forms such as hydrochlorides. The compound comprises at least two primary or secondary amino groups, with some embodiments comprising at least four primary or secondary amino groups, and the structural scope is defined by Formula II-based substituent and ring-formation options, including R1a and R1b, R2a-R2d, Rm, L1 and L2, R3, R4, R5, and related group selections.
The disclosure describes biocidal polyamine compounds with hydrophobic phenyl groups and hydrophilic polyamine chains, including hydrophobic-hydrophilic synergy and triple-action activity against biofilms. It also reports antimicrobial activity, biofilm dispersion, and unexpectedly superior biofilm eradication and dispersal performance.
Claims Coverage
The consolidated claim coverage centers on one independent method claim for dispersing or killing a biofilm on a subject, with dependent claims refining the biofilm type, composition/formulation form, anatomical surface, patient or condition context, and amino-group count. The inventive features combine the administration route, the anti-biofilm composition, and the structurally defined biocidal polyamine compound.
Biofilm dispersing or killing by administration of an anti-biofilm composition
A method for dispersing or killing a biofilm on a subject by topically, orally, transmucosally, vaginally, or rectally administering an anti-biofilm composition to a surface of the subject, thereby effectively dispersing or killing the biofilm.
Anti-biofilm composition with pharmaceutically acceptable carrier and therapeutically effective biocidal polyamine compound
The anti-biofilm composition comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of a biocidal polyamine compound, optionally as a salt thereof.
Defined biocidal polyamine structural scope with multiple amino groups
The biocidal polyamine compound is defined by Formula II-based structural selections, including R1a and R1b, R2a-R2d, Rm, L1 and L2, R3, R4, R5, and related group options, and comprises at least two primary or secondary amino groups, with some claim refinements requiring at least four.
Biofilm includes an antibiotic-resistant bacterial species
The method is wherein the biofilm includes an antibiotic-resistant bacterial species.
Anti-biofilm composition formulated as an aerosol spray, solution, suspension, gel, paste, cream, or foam
The anti-biofilm composition is formulated as an aerosol spray, solution, suspension, gel, paste, cream, or foam.
Administration to a specified anatomical surface
The method is performed on a dermal surface, mucosal surface, oral surface, urinary tract surface, vaginal tract surface, or lung surface.
Treating a patient with a biofilm-related disorder
The method further includes treating a patient who has a biofilm-related disorder.
Overall, the claims cover administering a carrier-based anti-biofilm composition containing a structurally defined biocidal polyamine compound to disperse or kill a biofilm, with dependent claims narrowing the biofilm, formulation, anatomical site, and patient context, and in some embodiments increasing the amino-group requirement.
Stated Advantages
Effectively dispersing or killing a biofilm.
Unexpectedly superior biofilm eradication and biofilm dispersal performance via hydrophobic-hydrophilic synergy.
Reduced opportunity for resistance development.
Increasing the number of polyamine chains lowers MIC/MBEC and improves EBEC versus traditional therapies.
Non-hemolytic behavior for certain compounds.
In vitro antimicrobial activity is shown for selected compounds.
Cytotoxicity screening outcomes are reported as dilution-dependent pass/fail.
Documented Applications
Topical, oral, transmucosal, vaginal, or rectal treatment of a subject's surface to disperse or kill a biofilm.
Treatment of biofilm-related disorder.
Biofilm inhibition and prevention.
In vitro biofilm dispersion testing on Ti coupons with MRSA biofilms.
Use with a hyaluronate hydrogel for agar diffusion testing showing inhibition zones.
Hemolysis testing to support a non-hemolytic grade for certain compounds.
Cytotoxicity screening using an MEM elution assay with L-929 cells.
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