Continuous methods for treating liquids and manufacturing certain constituents (e.g., nanoparticles) in liquids, apparatuses and nanoparticles and nanoparticle/liquid solution(s) resulting therefrom

Inventors

Pierce, David KyleMortenson, Mark G.Bryce, David A.

Assignees

Clene Nanomedicine Inc

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Publication Number

US-9387452-B2

Patent

Publication Date

2016-07-12

Expiration Date


Abstract

This invention relates generally to novel methods and novel devices for the continuous manufacture of nanoparticles, microparticles and nanoparticle/liquid solution(s). The nanoparticles (and/or micron-sized particles) comprise a variety of possible compositions, sizes and shapes. The particles (e.g., nanoparticles) are caused to be present (e.g., created and/or the liquid is predisposed to their presence (e.g., conditioned)) in a liquid (e.g., water) by, for example, preferably utilizing at least one adjustable plasma (e.g., created by at least one AC and/or DC power source), which plasma communicates with at least a portion of a surface of the liquid. At least one subsequent and/or substantially simultaneous adjustable electrochemical processing technique is also preferred. Multiple adjustable plasmas and/or adjustable electrochemical processing techniques are preferred. The continuous process causes at least one liquid to flow into, through and out of at least one trough member, such liquid being processed, conditioned and/or effected in said trough member(s). Results include constituents formed in the liquid including micron-sized particles and/or nanoparticles (e.g., metallic-based nanoparticles) of novel size, shape, composition, zeta potential and properties present in a liquid.

Core Innovation

The invention relates to water-based compositions and water-based liquids comprising silver constituents and zinc constituents in water, and in some embodiments nitrogen oxides in the water. The compositions specify silver constituents comprising silver ions and silver nanoparticles, zinc constituents comprising zinc ions, and defined constituent amounts and a zinc-to-silver amount ratio varying from 8:1 to 0.5:1.

A substantially continuous process is used to make the water-based composition containing silver and zinc constituents in water. Water is flowed through trough members while plasma and downstream electrochemical reactions produce silver species selected from silver ions and silver nanoparticles and zinc ions, and the produced silver-based constituents and zinc-based constituents are mixed to form the water-based composition.

The invention also describes a continuous liquid-processing platform for manufacturing and modifying nanoparticles and/or microparticles in a liquid, including metallic-based particles, such as in water. Adjustable plasma processing and in-line adjustable electrochemical processing downstream are described, with operating variables influencing nanoparticle properties including size, shape, composition, and zeta potential.

An apparatus arrangement is described that includes trough members with different cross-sectional shapes, controllable atmosphere/enclosure sections, and controllable electrode positioning/actuation to adjust plasma distance and intensity within a bounded range determined by the breakdown electric field. The controllable atmosphere is stated to tune plasma species, and expected plasma-generated chemical species include ozone, nitrogen oxides, and OH-related species.

Claims Coverage

The independent claims define three related inventive features: a substantially continuous process, a water-based composition with nitrogen oxides, and a water-based liquid with defined silver and zinc constituent concentrations and ratio. Across the independent claims, the core inventive features are the specified ppm ranges for silver constituents and zinc constituents, the zinc-to-silver amount ratio varying from 8:1 to 0.5:1, and the process-based generation and mixing of silver and zinc constituents.

Substantially continuous sequential silver-plasma and zinc-plasma production with downstream electrochemical reactions

A process in which water is flowed through at least one trough member while creating a plasma between a metallic silver-plasma-forming electrode and at least a portion of the upper surface of the water, followed by electrochemical reaction at downstream metallic silver-based electrodes to produce silver species selected from silver ions and silver nanoparticles; second water is flowed through second trough members while creating a plasma between a metallic zinc-plasma-forming electrode and at least a portion of the upper surface of the second water, followed by electrochemical reaction at downstream metallic zinc-based electrodes to produce zinc ions; and the produced silver-based constituents and zinc-based constituents are mixed such that the zinc-to-silver ratio varies from 8:1 to 0.5:1.

Water-based composition with nitrogen oxides and defined silver and zinc constituents

A water-based composition comprising water; silver constituents comprising silver ions and silver nanoparticles present in an amount of 1 ppm to 20.6 ppm; zinc constituents comprising zinc ions present in an amount of 0.5 ppm to 20 ppm; a ratio of the amount of zinc constituents to silver constituents varying from 8:1 to 0.5:1; and nitrogen oxides in the water.

Water-based liquid with defined silver and zinc constituent concentrations

A water-based liquid comprising water; silver constituents comprising silver species selected from the group consisting of silver ions and silver nanoparticles present in an amount of 7.13 ppm to 20.6 ppm; and zinc constituents comprising zinc ions present in an amount of 12.7 ppm to 20 ppm, wherein a ratio of the amount of zinc constituents to said silver constituents varies from 8:1 to 0.5:1.

The independent claims define compositions or liquids that include silver ions and silver nanoparticles and zinc ions with specified ppm ranges and a zinc-to-silver ratio varying from 8:1 to 0.5:1, and they further cover, in separate independent claim language, nitrogen oxides in the water and a substantially continuous process that sequentially forms silver species via silver plasma and downstream silver electrochemical reaction, then forms zinc ions via zinc plasma and downstream zinc electrochemical reaction, followed by mixing.

Stated Advantages

Some test solutions show relative efficacy ≥1 against biological test targets in the reported MIC/MID interpretation tables.

Example 19 reports viral titer reduction and log reduction for duck hepatitis B virus (DHBV) using GR-05 and GR-08.

Example 19 reports no observed cytotoxicity at assayed dilutions.

Enables continuous manufacture and modification of nanoparticles/microparticles in a liquid.

Allows adjustable plasma generation between an electrode above the liquid surface and the liquid surface acting as an electrode via dielectric breakdown/Taylor cones.

Provides optional in-line adjustable electrochemical processing downstream for further modification of nanoparticles/microparticles.

Enables controlling nanoparticle properties such as size, shape, composition, and zeta potential through operating variables.

Antibacterial performance measured by MIC and MID50 against Gram-positive and Gram-negative bacteria and fungi.

Antiviral efficacy measured as ≥99.99% reduction against duck hepatitis B virus after 6 hours and ≥4.0 log10 reduction.

Anti-parasitic activity against Trypanosoma b. rhodesiense and Plasmodium falciparum measured by IC50.

Documented Applications

Biological efficacy testing against clinical bacterial isolates and multiple fungi using MIC/MID interpretation for test solutions including GR-05 and GR-08.

Antiviral efficacy against duck hepatitis B virus (DHBV) using GR-05 and GR-08.

In vitro anti-parasitic/anti-malarial activities are described in later examples including targets identified as Trypanosoma b. rhodesiense (STIB 900) and Plasmodium falciparum (3D7 and Dd2).

Mechanistic binding study examining binding of silver constituents from GR-05 to a phospholipid bilayer (large unilamellar vesicles) to infer an equilibrium binding constant.

Characterization and biological testing are mentioned for nanoparticle solutions including silver, zinc, copper, and gold, with biological assay references such as E. coli, MIC, and cytotoxicity.

Use as an antibacterial composition tested against Gram-positive and Gram-negative bacteria and fungi using MIC/MID50 tables.

Use as an antiviral agent evaluated against duck hepatitis B virus.

Use as an anti-parasitic agent evaluated against Trypanosoma b. rhodesiense and Plasmodium falciparum.

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