Antimicrobial compositions
Inventors
Patton, Thomas • Brennan, James • Barrett, John Reginald • STAPLES, Ian
Assignees
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Abstract
Storage-stable compositions for generating antimicrobial activity are described. The compositions comprise an enzyme that is able to convert a substrate to release hydrogen peroxide, and an unrefined natural substance, such as a honey, that includes a substrate for the enzyme. In certain embodiments, the enzyme is a purified enzyme. In other embodiments, the substrate lacks catalase activity, and the enzyme is additional to any enzyme activity able to convert the substrate to release hydrogen peroxide that may be present in the unrefined natural substance. The storage-stable compositions do not include sufficient free water to allow the enzyme to convert the substrate. Use of the compositions to treat microbial infections and wounds is described, as well as methods for their production.
Core Innovation
The disclosure relates to sterile, storage-stable antimicrobial compositions that generate antimicrobial activity by exogenous addition of a hydrogen-peroxide-producing enzyme, including glucose oxidase, to an unrefined natural substrate that includes D-glucose. Key stability is achieved by preventing hydrogen peroxide generation during storage, so the enzyme does not convert the D-glucose while the composition is stored. At use, hydrogen peroxide generation occurs after dilution and conversion under conditions that permit the glucose oxidase to act.
The composition limits free water and/or sets water activity so the glucose oxidase does not produce hydrogen peroxide during storage, while still allowing antimicrobial activity after dilution at use. Variability reduction is emphasized by using substrates lacking catalase activity and/or lacking substrate-conversion activity, including pasteurized honey to inactivate catalase and endogenous glucose oxidase. The disclosure also emphasizes excluding ozonized honey or ozonized oil and avoiding added peroxidase, thereby keeping the composition substantially free of hydrogen peroxide.
The document further supports antimicrobial activity and includes rationales for wound-healing properties, including antimicrobial and wound-healing uses. Delivery and form factors are described, including dressings, solutions, and kits, and sterility is described as achievable by gamma irradiation. Extensive experimental support is described, including well-diffusion assays with phenol-equivalent potency control, stability after storage and irradiation, MIC/MBC and time-kill data for topical formulations, antiviral activity, and examples addressing wound infection outcomes and device-related colonization.
Claims Coverage
The provided independent claim is clm-00001, which recites a sterile storage-stable composition for generating antimicrobial activity with a hydrogen-peroxide-producing system constrained by water conditions and multiple exclusions. The claim includes several main inventive features, and the dependent claims further refine these features, including specifying honey as the sugar substance, pasteurization of the honey, powder form, irradiation sterilization, and quantitative glucose oxidase content.
Sterile glucose oxidase and D-glucose sugar substance system
A sterile storage-stable composition for generating antimicrobial activity comprising glucose oxidase and a sugar substance that lacks catalase activity and glucose oxidase activity and that includes D-glucose.
Water limitation for storage-stable antimicrobial activity
The composition does not include sufficient free water to allow the enzyme to convert the D-glucose, or has a water activity (aw) between 0.47 and 0.7.
Exclusion of ozonized honey or ozonated oil
The composition does not comprise ozonized honey or ozonated oil.
Substantially no hydrogen peroxide and no added peroxidase
The composition comprises substantially no hydrogen peroxide and does not comprise any added peroxidase.
Across the independent claim, the invention is defined by combining glucose oxidase with a sugar substance that includes D-glucose but lacks catalase and glucose oxidase activity, while enforcing storage stability by limiting free water or setting aw between 0.47 and 0.7, and excluding ozonized honey/oil, hydrogen peroxide, and any added peroxidase.
Stated Advantages
Enables a sterile storage-stable composition that generates antimicrobial activity.
Reduces variability by using substrates lacking catalase activity and/or lacking substrate-conversion activity.
Maintains storage stability by limiting conditions that would allow hydrogen peroxide generation during storage.
Broad organism coverage is indicated in the disclosure.
Supports wound-healing-related outcomes, including wound healing properties.
Device-related and clinical infection-related outcomes are described, including PICC-line colonization prevention and reduced Caesarean surgical site infection rate (historical comparison).
Documented Applications
Topical antimicrobial formulations are described, including formulations supported by well-diffusion assays and MIC/MBC and time-kill data, including a named topical example ("Surgihoney").
Antiviral activity is described.
Prevention of PICC-line colonization is described.
Reduction of Caesarean surgical site infection rate is described via a historical comparison.
Wound-healing and wound case examples are described, including rationales and related properties such as debridement, deodorising, and anti-inflammatory/immunostimulatory effects (e.g., IL-1) as stated in the disclosure.
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