Antimicrobial constructs
Inventors
Neff, Jennifer A. • McGuire, Joseph • Joshi, Pranav R.
Assignees
Oregon State University • ALLVIVO VASCULAR Inc
Publication Number
US-8598269-B2
Publication Date
2013-12-03
Expiration Date
2028-07-11
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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 provides an antimicrobial construct formed by linking known antimicrobial peptides, such as nisin or other lantibiotics, to a block copolymer (such as PLURONIC® F108 or an end-group activated polymer (EGAP)). This linkage results in antimicrobial coatings, gels, foams, powders, and emulsions by both physically entrapping the peptide and tethering it to the polymer. The entrapped peptides are released early for immediate antimicrobial action, while the tethered peptides remain for prolonged antimicrobial effectiveness.
The block copolymer contains one or more hydrophilic domains and at least one hydrophobic domain, and can be attached to substrate surfaces to provide a coating with combined antimicrobial and protein-resistant properties. The method enables modification of materials where a natural antibacterial component is used to kill microbes without promoting bacterial resistance. The copolymer can be crosslinked on substrates, and the peptide may be chemically bonded or physically entrapped depending on the embodiment, offering flexible application.
The problem addressed is that most medical device materials are susceptible to bacterial adhesion and biofilm formation, leading to infection, device failure, and costly interventions. Current antimicrobial surface technologies have issues such as the promotion of resistant bacteria, limited duration, and adverse reactions. The present invention overcomes these by preventing biofilm formation, supporting biocompatibility, and enabling application to a variety of substrates including irregular shapes and materials.
This invention further differentiates itself by allowing the robust combination of peptide antimicrobial activity with the anti-fouling and biocompatibility properties of block copolymer coatings. The products created may be utilized as surface coatings, incorporated into devices or gels, and retain activity for extended periods compared to peptide-only coatings, addressing the unmet needs of infection prevention and surface stability in medical and other settings.
Claims Coverage
The patent includes multiple inventive features based on four primary independent claims focusing on antimicrobial block copolymer constructs, antimicrobial coatings, compositions of matter with crosslinked block copolymers and antimicrobial components, and coated containers or substrates.
Antimicrobial block copolymer construct with tethered and entrapped antimicrobial component
An antimicrobial block copolymer construct in which: - A quantity of the antimicrobial component is attached to the block copolymer to form a flexible tether. - Another quantity of the antimicrobial component is physically entrapped in the polymer chains of the block copolymer. - The construct provides early antimicrobial activity through release of the entrapped component and prolonged activity via the tethered component. - The block copolymer is included in a solution, gel, foam, emulsion, or powder, and a portion of the block copolymer forms a crosslinked network.
Antimicrobial coating with block copolymer having both tethered and entrapped antimicrobial components crosslinked to the substrate
An antimicrobial coating comprising: - A substrate coated with a block copolymer where a portion of the block copolymer is crosslinked to the substrate. - The block copolymer contains one or more hydrophilic regions and one or more hydrophobic regions. - A portion of the copolymer comprises an antimicrobial component, with one part bound in a manner that forms a flexible tether to hydrophilic regions and another part entrapped in polymer chains of the hydrophilic regions.
Composition of matter of particles of block copolymer and antimicrobial component in a crosslinked network
A composition of matter comprising: - Particles of a block copolymer and an antimicrobial component where the block copolymer contains one or more hydrophilic regions and one or more hydrophobic regions. - A portion of the antimicrobial component is entrapped in polymer chains of the hydrophilic regions. - A portion of the block copolymer forms a crosslinked network. - The construct provides early antimicrobial activity by releasing the entrapped component and prolonged activity through the tethered component. - The block copolymer is included in a dispersion, gel, foam, emulsion or powder.
Container or material coated with crosslinked antimicrobial block copolymer construct
A container or material having a substrate coated with an antimicrobial block copolymer construct in which: - A portion of the block copolymer is crosslinked to the substrate. - A quantity of the antimicrobial component is attached to the block copolymer in a manner to form a flexible tether. - The construct provides antimicrobial activity through the tethered component.
The inventive features encompass antimicrobial constructs combining tethered and physically entrapped antimicrobial peptides within or on block copolymer networks, their use as coatings, compositions, or on containers and materials, with the copolymer and antimicrobial structure enabling immediate and prolonged antimicrobial activity.
Stated Advantages
Incorporates a natural antibacterial component that kills microbes without stimulating bacterial resistance.
Combines surface properties to prevent fibrin formation and occlusion.
Provides biocompatibility suitable for direct tissue interface.
Can be readily applied to a variety of materials and irregularly shaped objects.
PEO chains inhibit spontaneous elution and confer stability toward conformational rearrangement, translating to improved retention of activity.
Does not reduce the potency of available clinical antibiotics.
Allows broader use, increased safety, and reduced medical cost.
Provides early release of antimicrobial for immediate protection and prolonged action through tethering.
Block copolymers prevent protein adsorption, reducing non-specific biological interactions.
Documented Applications
Coating medical devices such as catheters, drug delivery pumps, vascular access devices, neural stimulation devices, intubation tubes, sutures, shunts, drainage tubes, feeding tubes, orthopedic devices, dental devices, extracorporeal circulation devices, and filtration devices.
Coating tissue products, including heart valves, to inhibit infection and potentially reduce calcification.
Coating storage containers for food packaging, blood bags, proteins, or pharmaceuticals to reduce the chance of bacterial infection and protein degradation.
Incorporation in solutions for cleaning medical equipment, antiseptic or sterile environments, and food preparation equipment.
Coating personal and industrial products such as mouth guards, orthodontic devices, face or breathing masks, pacifiers, contact lenses, food packaging, water containers, computer keyboards, telephones, steering wheels, health club equipment, whirlpool spas, humidifiers, decorative fountains, and hot water tanks.
Treatment of cooling towers, whirlpool spas, steam baths, filtration devices, and water lines in clinical and manufacturing settings.
Use as wound healing gels that can protect wounds and be combined with growth factors or anti-inflammatory agents for aiding in healing, especially for diabetic ulcers and burns.
Addition to foam cleaning solutions to provide antimicrobial properties.
Prevention of surgical adhesions via modified PLURONIC® gels with antibacterial properties.
Addition to toothpaste or mouthwash for lasting oral antimicrobial protection.
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