DispersinB™, 5-fluorouracil, deoxyribonuclease I and proteinase K-based antibiofilm compositions and uses thereof
Inventors
Madhyastha, Srinivasa • Gawande, Purusbottam • LoVetri, Karen • Yakandawala, Nandadeva • Kaplan, Jeffrey
Assignees
Publication Number
US-8617542-B2
Publication Date
2013-12-31
Expiration Date
2029-04-03
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Abstract
The present invention provides antibiofilm composition comprising two or more agents selected from the group consisting of DispersinB™, 5-Fluorouracil, Deoxyribonuclease I and Proteinase K for preventing growth and proliferation of biofilm-embedded microorganisms in wound care, oral care, and disease-related infections and methods of treatment in mammals. The invention further provides methods for preparing medical devices, and wound care devices using an antibiofilm composition comprising two or more antimicrobial agents selected from the group consisting of DispersinB™, 5-Fluorouracil, Deoxyribonuclease I and Proteinase K.
Core Innovation
The invention provides an antibiofilm composition comprising two or more agents selected from DispersinB™, 5-Fluorouracil, Deoxyribonuclease I (DNase I), and Proteinase K. These compositions are designed to prevent growth and proliferation of biofilm-embedded microorganisms. The invention includes methods of treatment in mammals, as well as preparation of medical and wound care devices using such compositions.
The problem addressed by the invention arises from the difficulty in treating infections associated with biofilms, which are microbial communities protected by an extracellular matrix. Biofilms in wounds, medical devices, and oral infections lead to infection persistence, delayed healing, increased treatment costs, and pose significant challenges in healthcare systems globally. Microorganisms in biofilms display enhanced resistance to antibiotics and antimicrobials, making infections hard to eradicate using known techniques.
The compositions combine agents with distinct mechanisms: DispersinB™ disperses biofilm matrix polysaccharides; 5-Fluorouracil acts as an antimicrobial by inhibiting thymidylate synthase; DNase I degrades extracellular DNA critical for biofilm integrity; and Proteinase K cleaves peptide bonds in biofilm proteins. The combined use of these agents at relatively low concentrations achieves enhanced antibiofilm and antimicrobial effects, overcoming the protective barriers of biofilms and improving treatment efficacy.
Claims Coverage
The patent discloses multiple independent claims focusing on compositions comprising multiple antibiofilm agents and their applications.
Composition comprising Dispersin B®, 5-fluorouracil, and deoxyribonuclease I or fragment thereof
A composition including Dispersin B® (or its variant), 5-fluorouracil, and deoxyribonuclease I (or active fragment) as antibiofilm agents that work synergistically to inhibit biofilm-embedded microorganisms.
Addition of Proteinase K to the composition
Inclusion of Proteinase K to the composition of Dispersin B®, 5-fluorouracil, and deoxyribonuclease I to enhance biofilm dispersion and microorganism inhibition.
Use of the composition in wound care devices and formulations
Incorporation of the antibiofilm composition into ointments, gels, lotions, various wound dressings, and spray applicators to treat biofilms associated with wounds.
Coating or treating medical devices with the composition
Methods for preparing medical devices, including indwelling catheters and other implantable or insertable devices, by coating, incorporating, or treating surfaces with the antibiofilm composition to prevent device-related infections.
Methods of inhibiting proliferation of biofilm-embedded microorganisms in mammals
Administration of the composition to inhibit biofilm-embedded gram-positive and gram-negative bacteria and fungi in mammals, including treatment of disease-related infections such as cystic fibrosis and oral infections.
The independent claims cover the antibiofilm composition comprising DispersinB™, 5-fluorouracil, DNase I, optionally with Proteinase K, their incorporation in wound care formulations and devices, coating of medical devices for infection prevention, and methods of treating biofilm-related infections. These claims collectively emphasize the use of multi-agent compositions to overcome biofilm-mediated resistance and improve antimicrobial effectiveness.
Stated Advantages
Enhanced antibiofilm activity at remarkably low concentrations of active agents compared to their individual use.
Ability to inhibit growth and proliferation of biofilm-embedded microorganisms, including both bacterial and fungal species.
Improved penetration and disruption of biofilm matrices, allowing better access of antimicrobials to embedded microbes.
Versatility of the compositions for use in various forms such as wound gels, dressings, coatings on medical devices, and oral care products.
Potential to decrease treatment costs and improve healing outcomes by effectively managing biofilm-associated infections.
Documented Applications
Preventing growth and proliferation of biofilm-embedded microorganisms in wound care, including various wounds such as surgical wounds, burns, ulcers including diabetic and pressure ulcers.
Treatment of oral infections and diseases such as dental plaque, periodontal diseases, dental caries, mucosal infections, and oral cancers.
Treatment of disease-related infections caused by biofilms, including infections associated with cystic fibrosis.
Preparation, coating, or treatment of medical devices like indwelling catheters, pacemakers, prosthetic heart valves, prosthetic joints, voice prostheses, contact lenses, and other implantable or insertable devices to prevent biofilm formation and device-related infections.
Use in wound care devices such as non-resorbable gauze/sponge dressings, hydrophilic wound dressings, occlusive wound dressings, hydrogel wound and burn dressings, spray applicators, ointments, lotions, and coated sutures.
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