Antimicrobial-antibiofilm compositions and methods of use thereof
Inventors
Gawande, Purushottam V. • LoVetri, Karen • Yakandawala, Nandadeva • Froehlich, Gordon • Madhyastha, Srinivasa
Assignees
Publication Number
US-10357470-B2
Publication Date
2019-07-23
Expiration Date
2033-04-26
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Abstract
Compositions comprising chelating agents, metal ion salts, gelling agents or a buffer, antimicrobials, antibiofilm agents and a pH adjuster or a buffer for the prevention and treatment of wound infections and food-borne diseases involving bacterial biofilms are disclosed. The anti-infective properties of a composition include reduction or killing of anaerobic/aerobic/facultative gram-negative and gram-positive wound infection associated bacteria occurring in polymicrobial biofilms. The composition may be in the form of lotion, cream, ointment, dressing, bandage, rinse, soak, gel, spray, or other suitable forms, including certain devices. Additionally, the invention offers an efficient method of delivering the formulated composition containing one or two chelating agents or chelating agents alone or in combination with a metal ion salt using either a nanoparticle or other efficient delivery systems.
Core Innovation
The invention provides compositions and methods comprising chelating agents, metal ion salts, antimicrobials, antibiofilm agents, gelling agents or buffers, and pH adjusters for the prevention and treatment of wound infections and food-borne diseases involving bacterial biofilms. The compositions demonstrate anti-infective properties including reduction or killing of anaerobic, aerobic, and facultative gram-negative and gram-positive bacteria that form polymicrobial biofilms in wounds. The compositions can be formulated into lotions, creams, ointments, dressings, bandages, rinses, gels, sprays, and other forms, including delivery via nanoparticles or other efficient systems.
The problem addressed by the invention is the challenge of treating wound infections complicated by bacterial biofilms, which are highly resistant to antibiotics, antimicrobials, and the host immune system. Chronic wounds are often colonized by polymicrobial communities forming biofilms, which delay healing and increase trauma and cost. Established antimicrobial treatments often fail to resolve these biofilm-associated infections effectively. Additionally, in food processing, there is a need for antimicrobials that are safe for humans and provide long-lasting antimicrobial power to prevent contamination of meat products and equipment, avoiding harmful residues associated with conventional agents like sodium hypochlorite.
The invention further provides efficient formulations combining two or more chelating agents and one or two metal ion salts that produce enhanced antimicrobial and antibiofilm activity at lower concentrations than traditionally required. It discloses specific embodiments including the use of EDTA and sodium citrate as chelating agents, combined with zinc salts such as zinc chloride or zinc sulfate, to inhibit bacterial and fungal growth and biofilm formation. These compositions can be used not only for wound care but also as disinfectants in food and meat processing, medical instruments, cosmetics, and veterinary treatments.
Claims Coverage
The patent contains one independent claim focusing on a specific composition for inhibiting biofilm formation involving certain fungi and bacteria, with multiple dependent claims detailing composition concentration ranges, components, preparation forms, delivery methods, and uses.
Composition comprising specific concentrations of EDTA salt and sodium citrate
A composition for inhibiting biofilm formation caused by Malassezia pachydermatis, Staphylococcus aureus, or Malassezia furfur comprising EDTA salt at about 0.5 mg/ml and sodium citrate at between about 3.2 mg/ml to about 6.4 mg/ml of the composition.
EDTA salt as disodium or tetrasodium salt
The EDTA salt in the composition is specifically disodium or tetrasodium EDTA.
Composition prepared with optional ingredients
The composition optionally includes one or more ingredients selected from water, a buffer, a stabilizing agent, a gelling agent, a surfactant, herbals, vitamins, minerals, extracellular matrix components, antimicrobials, antibiotics, and pH adjusters.
Formulations in diverse application forms
The composition can be prepared as disinfecting solutions, dip solutions, lotions, creams, ointments, gels, sprays, dressings, gauzes, bandages, thermoreversible gel sprays, wraps, adhesives, tapes, soaks, shampoos, and balms.
Delivery via liposomes or nanoparticles
The composition can be delivered using liposome or nanoparticle delivery systems to enhance stability and efficacy.
Composition including additional anti-infective compounds
The composition may further include an anti-infective compound selected from alginate lyase, nisin, lactoferricin, serotransferrin, ovotransferrin, ovalbumin, ovomucoid, protamine sulfate, chlorhexidine, cetylpyridinium chloride, triclosan, silver sulfadiazine, benzalkonium chloride, hydrogen peroxide, citric acid, potassium citrate, 5-fluorouracil, cis-2-decenoic acid, DNase I, proteinase K, silver, gallium, bacteriocins, antimicrobial peptides, and enzymes that cleave poly-B-1,6-N-acetylglucosamine.
Methods of preventing or treating wound infections
Methods comprising topical or non-topical application of the composition to treat or prevent wound infections including various infections such as cuts, bruises, surgical sites, lacerations, abrasions, punctures, incisions, gunshots, burns, pyoderma, otitis media and externa, mastitis, atopic dermatitis, eczema, pressure ulcers, venous and artery leg ulcers, and diabetic foot ulcers.
Multiple applications and broad subject use
The treatment method may include multiple applications and is applicable to humans, domestic animals, farm animals, zoo animals, pets, and various named animal species.
Methods of preventing or treating meat spoilage and disinfecting meat
Methods comprising topical or non-topical use of the composition on meat or meat products for preventing or treating spoilage and disinfecting meat.
Use on sausage casing materials
Use of the composition on intestines or intestinal parts of animals used for sausage casings and on collagen or cellulose used for making artificial sausage casings.
Application methods in meat processing
Topical or non-topical application methods including coating, spraying, misting, injecting, soaking, flushing, dipping, and rinsing.
The claims cover a composition with defined concentrations of EDTA salt and sodium citrate to inhibit biofilms of specified microbes, optionally combined with various additives, delivered through diverse formulations and methods, and applied for treatment of wound infections and meat spoilage prevention.
Stated Advantages
The compositions provide enhanced inhibitory effects on bacterial and fungal biofilm formation at lower concentrations of chelating agents and metal salts than previously required.
The anti-infective compositions effectively reduce and disrupt polymicrobial biofilms associated with acute and chronic wound infections and food-borne diseases.
The compositions have generally recognized as safe (GRAS) status and use food and feed additive ingredients, minimizing antibiotic resistance concerns and safety issues.
The invention provides formulations in multiple forms suitable for various delivery methods, including novel nanoparticle or liposome delivery for enhanced stability and efficacy.
The compositions exhibit broad-spectrum activity against a wide range of Gram-positive and Gram-negative wound and food-borne pathogens, including antibiotic-resistant strains.
Documented Applications
Prevention and treatment of acute and chronic wound infections in humans and animals, including infections associated with cuts, bruises, surgical sites, lacerations, burns, pyoderma, atopic dermatitis, eczema, pressure ulcers, leg ulcers, and diabetic foot ulcers.
Disinfection of fruits, vegetables, meat products, and food/meat processing facilities, as well as hospitals, barns, and medical instruments.
Veterinary applications for treating infections such as mastitis and otitis in domestic and farm animals.
Prevention and treatment of meat spoilage via topical or non-topical use on meat or meat products including beef, pork, lamb, goat, horse, chicken, and fish, as well as on sausage casing materials.
Use as disinfectants, cosmetics including shampoos, antimicrobial body lotions and creams, and wound care products like lotions, gels, sprays, bandages, dressings, wraps, gauze, tapes, adhesives, and wound irrigating devices.
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