Antimicrobial constructs
Inventors
Neff, Jennifer A. • McGuire, Joseph • Joshi, Pranav R.
Assignees
Allvivio Vascular Inc • Oregon State University • ALLVIVO VASCULAR Inc
Publication Number
US-10165773-B2
Publication Date
2019-01-01
Expiration Date
2028-07-11
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The invention is based on the recognition that known antimicrobial compounds, such as nisin or other lantibiotics, can be made to form a long lasting antimicrobial surface coating by linking the peptide with a block polymer, such as PLURONIC® F108 or an end group activated polymer (EGAP) in a manner to form a flexible tether and/or entrap the peptide. The entrapped peptide provides antimicrobial action by early release from entrapment while the tethered peptide provides longer lasting antimicrobial protection. Antimicrobial gels and foams may be prepared using the antimicrobial peptide containing block copolymers.
Core Innovation
The invention relates to antimicrobial constructs that incorporate a protein resistant component and an active antimicrobial component. Specifically, it uses a block copolymer containing one or more hydrophilic domains and at least one hydrophobic domain, such as a PLURONIC® surfactant or an end group activated polymer (EGAP), to which an antimicrobial peptide, such as nisin or another lantibiotic, is tethered. The copolymer can be formulated as coatings, gels, foams, solutions, and other products, imparting antimicrobial properties to the surface or medium.
A central principle of the invention is that the antimicrobial peptide can be covalently linked to the block copolymer—thereby creating a flexible tether that keeps the peptide active longer—or physically entrapped within the polymer network for early release and antimicrobial action. This dual approach allows both immediate and sustained antimicrobial effects. The protein resistant nature of the copolymer also serves to inhibit non-specific protein adsorption and biofilm formation.
The background identifies the problem of infections, thrombosis, and biofilm formation on biomaterials and medical devices. It notes that previous technologies either prevent bacterial adhesion or kill bacteria by releasing agents but are often ineffective long-term, may promote antimicrobial resistance, or are limited by biocompatibility and applicability to irregular surfaces. The present invention addresses these needs by enabling biocompatible, broadly applicable, non-leaching antimicrobial coatings, with reduced risk of resistance development and the additional benefit of inhibiting thrombus formation.
Claims Coverage
The patent comprises five independent claims, each introducing a unique inventive feature relating to antimicrobial constructs and their application.
Method of coating a substrate using an antimicrobial construct
A method which involves providing an antimicrobial construct made from an antimicrobial block copolymer (comprising a block copolymer component coupled to an antimicrobial peptide component), applying the construct to a substrate such that a first portion of the copolymer adsorbs to the surface and a second portion forms a flexible tether to the peptide, resulting in greater antimicrobial activity versus applying the peptide alone.
Method of using an antimicrobial construct to prevent or inhibit biofilm formation
A method wherein an antimicrobial construct (comprising an antimicrobial block copolymer with peptide) is applied to a substrate so that the copolymer forms a flexible tether for the antimicrobial peptide and adsorbs to the substrate surface to inhibit biofilm formation, imparting greater antimicrobial activity than the peptide alone.
Composition for treating or preventing microbial growth with particles of an antimicrobial construct
A composition comprising a dispersion, gel, foam, emulsion, or powder containing particles of an antimicrobial construct (block copolymer coupled to antimicrobial peptide), where the copolymer both adsorbs or bonds to the substrate and forms a flexible tether to the peptide, thereby enhancing antimicrobial activity compared to the peptide alone.
Substrate coated with an antimicrobial coating comprising a block copolymer construct
A coated substrate where an antimicrobial coating made of a block copolymer construct with tethered antimicrobial peptide is adhered to the substrate, such that the copolymer adsorbs/bonds to the surface and the peptide is flexibly tethered, providing antimicrobial activity greater than the peptide alone.
Coated substrate containing a lantibiotic and a covalently coupled block copolymer
A coated substrate comprising a first antimicrobial agent that is a lantibiotic covalently coupled to a block copolymer (with a first hydrophobic portion adhering/bonding to the substrate and a second portion forming a flexible tether to the lantibiotic), wherein the coating imparts greater antimicrobial activity than a coating with the lantibiotic alone. An optional second antimicrobial agent may be entrapped in the copolymer.
The inventive features cover novel antimicrobial constructs comprising block copolymers and antimicrobial peptides, their use in forming coatings and compositions imparting enhanced antimicrobial and anti-biofilm activity to substrates, medical devices, and topical formulations.
Stated Advantages
Incorporates a natural antibacterial component that kills bacteria or microbes without stimulating bacterial resistance.
Combines surface properties to prevent fibrin formation and occlusion.
Is biocompatible and can be directly interfaced with tissue.
Can be readily applied to a variety of materials and irregularly shaped objects.
PEO chains confer stability for improved retention of antimicrobial activity.
Does not pose a risk for decreasing the potency of clinical antibiotics by using a natural, alternative antimicrobial.
Allows for broader use, increased safety, and reduced medical cost.
The coating process is simple and adaptable for different applications.
Provides early release and longer-term antimicrobial activity via entrapped and tethered peptides.
Documented Applications
Coating medical devices such as catheters, drug delivery pumps, vascular access devices, neural intervention devices, intubation tubes, sutures, shunts, drainage tubes, feeding tubes, extracorporeal devices, dental devices, tubing, and fittings.
Coating tissue products including heart valves and tissue scaffolds, potentially reducing infection and calcification.
Coating storage containers for food packaging, blood, proteins, or pharmaceuticals to reduce bacterial contamination and protein degradation.
Cleaning solutions for medical equipment, items in antiseptic or sterile environments, and food preparation equipment.
Coating personal and industrial products, such as mouth guards, orthodontic devices, masks, pacifiers, contact lenses, food preparation surfaces, water containers, keyboards, telephones, steering wheels, health club equipment, whirlpool spas, and humidifiers.
Use in foams, gels, and powders to create topical antimicrobial products for application to skin, wounds, or surgical sites.
In wound healing gels with biocompatible properties and high water content, suitable for diabetic ulcers and burns.
Inclusion in oral care products such as toothpaste and mouthwash to provide lasting antimicrobial protection.
Combining with metal-chelating block copolymers to broaden antimicrobial spectrum and provide anti-thrombotic and anti-proliferative functions.
Coating of food products or food packaging, leveraging approval of nisin and PLURONIC® for food use to provide antimicrobial activity in the food industry.
Interested in licensing this patent?