Bactericidal methods and compositions
Inventors
Dong, Pu-Ting • Hui, Jie • Cheng, Ji-Xin • ZHU, Yifan
Assignees
Pulsethera Inc • General Hospital Corp
Publication Number
US-11110296-B2
Publication Date
2021-09-07
Expiration Date
2040-01-31
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Methods of the present invention comprise photoinactivation of catalase in combination with low-concentration peroxide solutions and/or ROS generating agents to provide antibacterial effects.
Core Innovation
The invention provides methods for treating infections and disinfecting surfaces by photoinactivation of catalase in catalase-positive microbes using blue light having a wavelength of about 400 nm to about 430 nm, specifically around 410 nm. This photoinactivation renders the catalase enzyme inactive, making microbial pathogens highly susceptible to reactive oxygen species (ROS)-generating antimicrobials, low-concentration peroxide solutions, and immune cell attacks. The method involves applying light to a tissue or inanimate surface contaminated with such microbes, followed by contacting the site with a diluted peroxide solution and/or ROS generating agents, producing synergistic antimicrobial effects.
The problem addressed by the invention arises from the global health threat of antibiotic resistance, which kills an estimated 700,000 people annually worldwide and is predicted to worsen significantly by 2050. Pathogens acquire resistance more rapidly than new antibiotics are introduced, creating an urgent need for unconventional antimicrobial strategies. Catalase, an enzyme widespread among aerobic pathogens, scavenges hydrogen peroxide to protect microbes from oxidative damage caused by reactive oxygen species, thereby reducing the efficacy of ROS-mediated antimicrobial effects. The invention solves this problem by photoinactivating catalase to overcome microbial defenses and enhance antimicrobial and immune-mediated killing.
The methods of the invention specifically involve: applying pulsed or continuous wave blue light, preferably around 410 nm wavelength and a dose from about 5 J/cm2 to about 200 J/cm2, to inactivate catalase; then administering a low-concentration hydrogen peroxide solution (between about 0.03% and 0.3%) and/or ROS generating agents such as antibiotics (tobramycin, β-lactams, aminoglycosides, fluoroquinolones, azoles, polyenes) or metals (silver cation, gold nanoparticles) to the treated tissue or surface. The synergy among photoinactivation, peroxide solutions, and ROS-generating agents results in substantial reductions of bacterial or fungal burdens, including in drug-resistant strains, and assists immune cells in eliminating intracellular pathogens.
Claims Coverage
The claims include one independent claim focusing on a method of disinfecting an inanimate surface contaminated with a catalase-positive microbe by applying pulsed visible light and subsequently contacting the surface with a diluted peroxide solution. The inventive features relate to specific wavelengths, light doses, microbial types, peroxide concentrations, light sources, and materials of the inanimate surfaces.
Method of disinfecting inanimate surfaces by catalase photoinactivation
Applying pulsed visible light at a wavelength of 405 nm to 420 nm and a dose of about 5 J/cm2 or greater to inactivate catalase in catalase-positive microbes on inanimate surfaces; subsequently contacting the surface with a composition comprising a diluted peroxide solution to achieve disinfection.
Wavelength specificity for catalase photoinactivation
Choosing a wavelength of 410 nm to optimize photoinactivation of catalase and thereby enhance antimicrobial effect.
Light dose for effective catalase photoinactivation
Using a light dose of approximately 15 J/cm2 to achieve significant catalase inactivation on surfaces.
Type of light source for photoinactivation
Employing a pulsed nanosecond laser as the light source for delivering the specified wavelength and dose.
Diluted peroxide solution composition
Using a hydrogen peroxide solution between about 0.03% and about 0.3% concentration as the diluted peroxide solution for contacting the surface.
Material composition of the inanimate surface
Treating a variety of inanimate surface materials including metal, plastic, fabric, rubber, stone, composite surfaces, or wood.
Light dose range
Applying a dose of light ranging from about 5 J/cm2 to about 200 J/cm2 to effect catalase photoinactivation.
The claims cover a method for disinfecting inanimate surfaces contaminated with catalase-positive microbes by photoinactivating catalase with pulsed blue light at 405-420 nm, followed by treatment with diluted peroxide solutions, particularly hydrogen peroxide at low concentrations, using pulsed nanosecond lasers, applicable to diverse surface materials and using specified light doses.
Stated Advantages
Significantly enhances antimicrobial efficacy against catalase-positive bacteria and fungi, including drug-resistant strains.
Creates a synergistic effect between photoinactivation of catalase and low-concentration hydrogen peroxide or ROS-generating agents, leading to substantial microbial eradication.
Assists immune cells such as macrophages and neutrophils in eliminating intracellular pathogens by overcoming microbial defenses.
Photoinactivation by pulsed nanosecond laser light is more effective than continuous wave light and minimizes thermal damage to tissues.
Applicable to both treatment of infected tissues and disinfection of inanimate surfaces composed of various materials.
Documented Applications
Treating infected tissues of subjects, including skin, scalp, nails, and potentially internal tissues such as gastrointestinal and oral, vaginal, or nasal cavities.
Disinfecting inanimate surfaces contaminated with catalase-positive microbes, where surfaces may comprise metal, plastic, fabric, rubber, stone, composite materials, or wood.
Enhancing the killing efficacy of low-concentration hydrogen peroxide and ROS-generating antibiotics or antifungals against catalase-positive bacteria and fungi.
Assisting immune clearance of intracellular pathogens by macrophages and neutrophils.
Interested in licensing this patent?