Methods of use comprising a biocidal polyamine
Inventors
Williams, Dustin • Looper, Ryan • Jeyapalina, Sujeevini • Haussener, Travis • Sebahar, Paul R. • Reddy, Hari Kanna
Assignees
CURZA GLOBAL LLC • University of Utah Research Foundation Inc
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Publication Number
US-9220267-B2
Publication Date
2015-12-29
Expiration Date
Abstract
Compounds, compositions, and methods comprising a polyamine compound are described, which may be used to kill, disperse, treat, reduce biofilms, and/or 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 polyamine-based anti-biofilm compositions and methods for dispersing or killing a biofilm. An anti-biofilm composition comprises a biocidal polyamine compound selected from an enumerated group and a salt thereof, where the biocidal polyamine compound comprises at least four primary or secondary amino groups. The biocidal polyamine compounds are defined by chemical-structure parameters and variable substituent selections, including Ra, Rm, L, R3, R4, Y1/Y2, and Z1/Z2.
The disclosed biocidal polyamine compounds include amphipathic polyamine molecules having cationic residues with multiple primary or secondary amino groups and lipophilic or hydrophobic backbones. The document includes structural constraints and alternative ring-forming arrangements, and mentions backbone examples such as spermine, spermidine, norspermine, and norspermidine. The compositions are also described as anti-biofilm compositions and antimicrobial compositions.
The disclosure states that polyamine compounds are used to rapidly disperse and kill bacteria within biofilms, reduce biofilm reattachment and regrowth, and that increasing the number or content of primary or secondary amine groups enhances biofilm dispersing and antimicrobial activity. The invention further states that the compositions may be combined with existing antimicrobials.
Claims Coverage
The consolidated independent claim coverage centers on a method for dispersing or killing a biofilm by contacting the biofilm with an anti-biofilm composition containing a biocidal polyamine compound or salt thereof. The inventive features are the contacting step, the defined biocidal polyamine composition, and the requirement that the compound comprises at least four primary or secondary amino groups.
Contacting a biofilm with an anti-biofilm composition to disperse or kill
A method comprising contacting the biofilm with an anti-biofilm composition to disperse or kill the biofilm.
Anti-biofilm composition containing a biocidal polyamine compound and a salt thereof
The anti-biofilm composition comprises a biocidal polyamine compound selected from the enumerated biocidal polyamine compounds and a salt thereof.
Defined polyamine structure with at least four primary or secondary amino groups
The biocidal polyamine compound is defined by substituent and linker selections including Ra, Rm, L, R3, R4, Y1/Y2, and Z1/Z2, and comprises at least four primary or secondary amino groups.
The inventive coverage is directed to using an anti-biofilm composition containing a structurally defined biocidal polyamine compound or salt, with at least four primary or secondary amino groups, to disperse or kill a biofilm.
Stated Advantages
Dispersing or killing a biofilm.
Lower MIC with increasing polyamine chain number on a lipophilic backbone.
Improved biofilm eradication.
Strong reduction of MRSA biofilm compared with vancomycin failure described in the provided content.
Mechanistic intent of membrane-active, rapid kill, and nonspecific action to reduce resistance risk.
Enhanced biofilm dispersing and antimicrobial activity with increased primary or secondary amine content.
Reduced biofilm reattachment and regrowth.
Documented Applications
Experimental MIC/MBEC/EBEC assessment of biocidal polyamine compounds against planktonic bacteria and biofilms, including high-biomass biofilms on PEEK membranes.
Proof-of-concept elution from a polytherapy cream carrier producing zones of clearing.
Biofilm dispersion studies with MRSA biofilms on titanium coupons and SEM-based characterization.
Assessment of anti-biofilm activity for antibiotic-resistant bacterial species biofilm as a biological target context.
Medical surfaces and devices, including catheters, stents, and endoscopes.
Dispersing or killing a biofilm associated with antibiotic-resistant bacteria, including MRSA and A. baumannii, with effects described for mycobacteria.
Inhibiting biofilm formation by treating planktonic bacteria so that they do not incorporate into the biofilm.
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