Gold-based nanocrystals for medical treatments and electrochemical manufacturing processes therefor
Inventors
Mortenson, Mark Gordon • Pierce, D. Kyle • Bryce, David A. • Wilcox, Reed N. • Lockett, Anthony • Merzliakov, Mikhail
Assignees
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Publication Number
US-10980832-B2
Publication Date
2021-04-20
Expiration Date
Abstract
The present invention relates to novel gold nanocrystals and nanocrystal shape distributions that have surfaces that are substantially free from organic impurities or films. Specifically, the surfaces are “clean” relative to the surfaces of gold nanoparticles made using chemical reduction processes that require organic reductants and/or surfactants to grow gold nanoparticles from gold ions in solution.The invention includes novel electrochemical manufacturing apparatuses and techniques for making the gold-based nanocrystals. The invention further includes pharmaceutical compositions thereof and the use of the gold nanocrystals or suspensions or colloids thereof for the treatment or prevention of diseases or conditions for which gold therapy is already known and more generally for conditions resulting from pathological cellular activation, such as inflammatory (including chronic inflammatory) conditions, autoimmune conditions, hypersensitivity reactions and/or cancerous diseases or conditions. In one embodiment, the condition is mediated by MIF (macrophage migration inhibiting factor).
Core Innovation
The invention relates to treating a patient with multiple sclerosis by administering an effective amount of a pharmaceutically acceptable suspension comprising pharmaceutical grade water and at least one processing enhancer comprising sodium bicarbonate, with gold nanocrystals suspended in the water. The gold nanocrystals have surfaces that do not have organic chemical constituents adhered or attached to the surfaces, have a mode particle size of less than about 50 nm, and are present at a concentration of at least 2 ppm.
The suspension is characterized by a pH between about 5 to about 9.5, and the gold nanocrystals have a zeta potential of about -20 mV or lower at about 25° C. The zeta potential is determined by measuring the electrophoretic mobility of the gold nanocrystals in the suspension, and the suspension does not contain chloride ions.
In certain embodiments, the gold nanocrystals are shaped and comprise at least one low Miller index crystal plane selected from {111}, {110}, and {100}. The shaped gold nanocrystals comprise triangle and pentagon shapes, and other embodiments include additional shapes such as hexagons and diamond shapes.
Claims Coverage
The provided independent claims are clm-00001, clm-00003, clm-00005, and clm-00024. Across these independent claims, the coverage centers on administering to a multiple-sclerosis patient an effective amount of a pharmaceutically acceptable suspension containing surface-clean gold nanocrystals, with specified pH, electrophoretic mobility-based zeta potential thresholds, nanoscale mode particle size, a minimum gold nanocrystal concentration, and absence of chloride ions, with further morphology limitations in some claims.
Multiple-sclerosis treatment with a sodium bicarbonate suspension and surface-clean gold nanocrystals
A method for treating a patient with multiple sclerosis comprising administering an effective amount of a pharmaceutically acceptable suspension including pharmaceutical grade water, at least one processing enhancer comprising sodium bicarbonate, and gold nanocrystals suspended in the water, wherein the gold nanocrystals have surfaces without organic chemical constituents adhered or attached and have a mode particle size of less than about 50 nm at a concentration of at least 2 ppm.
Suspension pH and zeta potential defined by electrophoretic mobility with chloride-free formulation
The suspension has a pH of between about 5 to about 9.5, the gold nanocrystals have a zeta potential of about -20 mV or lower at about 25° C., the zeta potential is determined by measuring the electrophoretic mobility of the gold nanocrystals in the suspension, and the suspension does not contain chloride ions.
Oral pharmaceutical suspension with shaped gold nanocrystals and low Miller index crystal planes
A method for treating a patient with multiple sclerosis comprising administering orally a pharmaceutically acceptable suspension including water and NaHCO3 dissolved therein, wherein the shaped gold nanocrystals have surfaces without organic chemical constituents adhered or attached, have a mode particle size of less than about 50 nm, are present at a concentration of at least 2 ppm, are shaped, and comprise at least one low Miller index crystal plane selected from {111}, {110}, and {100}.
Collectively, the independent claims cover administration of a pharmaceutically acceptable, chloride-free suspension containing NaHCO3 or a processing enhancer and gold nanocrystals characterized by lack of organic chemical constituents on surfaces, sub-50 nm mode particle size, at least 2 ppm concentration, suspension pH constraints, and zeta potential thresholds measured by electrophoretic mobility at about 25° C. Additional claim coverage is defined by shaped morphologies and the presence of low Miller index crystal planes selected from {111}, {110}, and {100}.
Stated Advantages
Higher potency than Auranofin.
Potentially lower toxicity than Auranofin.
GMP cGMP-oriented manufacturing and broad pharmaceutical formulation/use routes including oral liquid suspension and stent reservoir applications.
Produces gold nanocrystals/nanocrystal suspensions with adjustable properties, including nanocrystal size distribution and zeta potential.
Provides gold nanocrystals with a clean nanocrystal surface that is substantially free from organic impurities.
Supports control over crystal growth and crystal planes/shapes, including extended low-index planes such as {111}, {100}, and {110}.
Documented Applications
Treatment of a patient with multiple sclerosis.
Oral administration of the pharmaceutical suspension for treating multiple sclerosis.
Stent reservoir application is described as a use route for the pharmaceutical formulation.
Use of an apparatus for creating adjustable plasmas to produce gold nanocrystals and nanocrystal suspensions/colloids with tunable properties.
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