Nanoparticle compositions and methods for treating or preventing tissue infections and diseases

Inventors

Tarbet, Bryon J. • Niedermeyer, William H.

Assignees

Evoq Nano Inc

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Publication Number

US-9839652-B2

Patent

Publication Date

2017-12-12

Expiration Date


Abstract

Stabilized multi-component antimicrobial compositions for treating tissue diseases, infections or conditions include a first and second set of differently sized and/or differently shaped metal nanoparticles, and a stabilizing agent. Compositions and treatment methods may be used for treating tissue diseases, infections or conditions caused by microbial infections, such as bacteria, viral, and/or fungal infections, or for preventing the infection of a wound, such as a cut, abrasion, ulcer, lesion, sore, and the like. The compositions and treatment methods disclosed herein may also be used as a prophylactic, and in some embodiments may be applied to otherwise healthy tissue in order to prevent or reduce the occurrence of a tissue disease, infection or condition.

Core Innovation

The invention relates to stabilized multi-component antimicrobial tissue treatments using at least two differently configured nonionic ground-state metal nanoparticle sets. The first set comprises laser ablation-made, nonionic, spherical-shaped solid metal core nanoparticles with mean particle size in the range of about 1 nm to about 20 nm and a narrow particle size distribution, in which at least about 99% of the spherical-shaped nanoparticles are within ±3 nm of the mean particle size. The first set comprises ground state silver and is described as part of a composition for killing a microbe associated with a tissue infection or tissue disease and/or treating such tissue infection or disease.

The composition further includes a second set of ground-state metal nanoparticles that differ from the first set by at least one of metal composition, process of preparation, particle size and particle size distribution, or nanoparticle shape. In the described embodiments, the second set comprises ground state gold. The spherical silver nanoparticles and the coral-shaped gold nanoparticles are presented as differently configured components that enable antimicrobial activity against microbes associated with tissue infections or tissue disease.

The invention also includes a stabilizing agent that prevents or reduces agglomeration of the metal nanoparticles as compared to a composition without the stabilizing agent, and is described as supporting stable multi-component nanoparticle treatment formulations. The document discusses mechanisms including disulfide (S—S) bond catalysis and oxidative protein cleavage, and for viruses, virus deactivation via protein coat glycoprotein attachment/denaturation. It further describes stabilizer and carrier choices such as natural polyphenols, oils, alcohols, and topical cream/gel/emulsion-type carriers, and it presents example treatment modalities including topical application, injection, and inhalation/nasal spray, including wound infection prophylaxis and treatment for microbes associated with medical devices.

Claims Coverage

The independent claims define nanoparticle compositions for killing microbes associated with tissue infections or treating tissue infections or diseases, using two sets of laser ablation-made nonionic ground-state metal nanoparticles (ground state silver spherical nanoparticles and ground state gold nanoparticles), together with a stabilizing agent to reduce agglomeration. Across the independent claims, the main inventive theme is the defined nanoparticle physical constraints combined with a stabilizing agent, and in one independent claim the coral-shaped gold component is stated to potentiate/enhance the spherical component’s effectiveness.

Two laser-ablated nonionic ground-state nanoparticle sets (silver and gold) with narrow spherical size distribution

A first set of laser ablation-made nonionic spherical-shaped solid metal core ground state silver nanoparticles having mean particle size about 1 nm to about 20 nm and a narrow particle size distribution in which at least about 99% of the spherical-shaped nanoparticles are within ±3 nm of the mean particle size; and a second set of ground state gold metal nanoparticles that differ from the first set by at least one of different metal, different process, different particle size and particle size distribution, or different shape, wherein the second set comprises ground state gold.

Stabilizing agent to prevent or reduce nanoparticle agglomeration

A stabilizing agent that prevents or reduces agglomeration of the metal nanoparticles as compared to a composition without the stabilizing agent.

Coral-shaped ground-state gold nanoparticles potentiate spherical nanoparticle activity

For treating a dermatological condition: a set of spherical-shaped metal nanoparticles; a set of coral-shaped metal nanoparticles made by laser ablation such that each is nonionic, has a non-uniform cross section, and has a globular structure with multiple non-linear strands joined together without right angles, with coral-shaped nanoparticles comprising ground state gold and having mean length about 15 nm to about 100 nm and at least 99% of the coral-shaped nanoparticles having a length within 30% of the mean length; and a stabilizing agent that prevents or reduces agglomeration of the spherical-shaped and coral-shaped metal nanoparticles as compared to a composition without the stabilizing agent, wherein the coral nanoparticles potentiate the activity of the spherical-shaped nanoparticles to enhance the effectiveness of the spherical-shaped nanoparticles.

Carrier plus two laser-ablated nonionic ground-state nanoparticle sets with defined zeta potential and narrow spherical size distribution

A carrier comprising one or more listed carriers; a first set of laser ablation-made nonionic spherical nanoparticles with solid metal cores, a zeta potential of at least 30 mV (absolute value), mean particle size about 1 nm to about 20 nm, and a narrow particle size distribution in which at least about 99% of the spherical metal nanoparticles are within ±3 nm of the mean particle size, wherein the first set comprises ground state silver; and a second set of ground state gold metal nanoparticles that differ from the first set by at least one of different metal, different process, different particle size and particle size distribution, or different shape, wherein the second set comprises ground state gold.

Overall, the independent claims require compositions that combine two differently configured laser ablation-made, nonionic ground-state metal nanoparticle sets (silver spherical and gold differing configuration), constrain nanoparticle shape and narrow size distributions, and include a stabilizing agent that prevents or reduces agglomeration; additionally, the coral-shaped gold component is stated to potentiate/enhance the spherical component’s effectiveness for dermatological conditions.

Stated Advantages

Prevents or reduces agglomeration of the metal nanoparticles as compared to a composition without the stabilizing agent.

Coral nanoparticles potentiate the activity of the spherical-shaped nanoparticles to enhance the effectiveness of the spherical-shaped nanoparticles.

Documented Applications

Killing a microbe associated with a tissue infection or tissue disease and/or treating the tissue infection or tissue disease associated with the microbe.

Treating a dermatological condition and/or killing a virus, bacteria, or fungus associated with a dermatological condition.

Wound infection prophylaxis and medical-device treatment to prevent MRSA infection.

Topical application, injection, and inhalation/nasal spray treatment modalities.

MRSA treatment associated with Staphylococcus aureus infection resolution as illustratively described in the document.

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