Gold-based nanocrystals for medical treatments and electrochemical manufacturing processes therefor
Inventors
Mortenson, Mark Gordon • Pierce, D. Kyle • Bryce, David A. • Dorfman, Adam R. • Wilcox, Reed N. • Lockett, Anthony • Merzliakov, Mikhail
Assignees
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Publication Number
US-9603870-B2
Publication Date
2017-03-28
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 provides clean gold nanocrystals having surfaces that do not have organic chemical constituents adhered or attached to the surfaces, and a pharmaceutical suspension comprising pharmaceutical grade water and at least one processing enhancer comprising sodium bicarbonate, with gold nanocrystals suspended in the water to form the suspension. The gold nanocrystals have a mode particle size of less than about 50 nm and are present at a concentration of at least 2 ppm by weight per volume, with some claim families specifying 2-200 ppm (w/v).
The suspension has defined pH and colloidal stability characteristics, including a pH between about 5 to about 9.5, and in some claims between about 8 to about 9.5. The gold nanocrystals have a zeta potential of about -20 mV or lower or about -30 mV or lower at about 25° C., determined by measuring the electrophoretic mobility of the gold nanocrystals in the suspension.
In shaped embodiments, the gold nanocrystals comprise low Miller index crystal planes selected from {111}, {110}, and {100}, with shape descriptors including triangle and pentagon shapes, and further hexagon, diamond, pentagonal bipyramids, decahedrons, icosahedrons, octahedrons, and fused tetrahedrons. The suspension does not contain chloride ions in some claim families, and the invention also relates to nucleation and growth of gold nanocrystals in aqueous solution and in a liquid using an adjustable plasma.
Claims Coverage
The partial content identifies four independent claims. Across these independent claims, the coverage centers on a sodium bicarbonate (NaHCO3)-processing-enhanced pharmaceutical suspension containing gold nanocrystals that meet defined surface, size, concentration, pH, zeta potential/electrophoretic mobility, and, in some claims, crystal-plane/shape and chloride exclusion constraints.
NaHCO3-processing-enhanced pharmaceutical suspension with surface-clean gold nanocrystals
A pharmaceutical suspension comprising pharmaceutical grade water and at least one processing enhancer comprising sodium bicarbonate, wherein gold nanocrystals are suspended in said water forming a suspension.
Gold nanocrystals free of adhered or attached organic chemical constituents
Gold nanocrystals having surfaces that do not have organic chemical constituents adhered or attached to said surfaces.
Defined nanocrystal mode particle size and concentration
Gold nanocrystals having a mode particle size of less than about 50 nm and being present in said suspension at a concentration of at least 2 ppm by weight per volume.
Suspension pH and electrophoretic mobility-determined zeta potential bound with no chloride ions
The suspension having a pH of between about 5 to about 9.5, the gold nanocrystals having a zeta potential of about -20 mV or lower at a temperature of about 25° C., said zeta potential being determined by measuring the electrophoretic mobility of the gold nanocrystals in the suspension, and the suspension does not contain chloride ions.
NaHCO3 processing medium with pH range and shaped gold nanocrystals meeting zeta potential and surface/size/concentration constraints
A pharmaceutical suspension comprising a suspension medium comprising pharmaceutical grade water and at least one processing enhancer comprising sodium bicarbonate dissolved therein, said suspension medium having a pH of between about 5 to about 9.5; and shaped gold nanocrystals having a zeta potential of about -20 mV or lower at a temperature of about 25° C., said zeta potential being determined by measuring the electrophoretic mobility of the shaped gold nanocrystals in the suspension, wherein said shaped gold nanocrystals have surfaces that do not have organic chemical constituents adhered or attached to said surfaces, have a mode particle size of less than about 50 nm, are present in said suspension at a concentration of at least about 2 ppm by weight per volume, and have shapes comprising low Miller index crystal planes.
Shaped gold nanocrystals with triangle and pentagon shapes plus defined electrophoretic mobility zeta potential and size constraint
A pharmaceutical suspension comprising a suspension medium comprising pharmaceutical grade water and sodium bicarbonate dissolved therein, said suspension medium having a pH of between about 5 to about 9.5; shaped gold nanocrystals having a zeta potential of about -30 mV or lower at a temperature of about 25° C., said zeta potential being determined by measuring the electrophoretic mobility of the shaped gold nanocrystals in the pharmaceutical suspension; and wherein said shaped gold nanocrystals have surfaces that do not have organic chemical constituents adhered or attached to said surfaces, have a mode particle size of less than about 30 nm, are present in said pharmaceutical suspension at a concentration of at least about 2 ppm by weight per volume, and comprise triangle and pentagon shapes.
NaHCO3 pharmaceutical suspension with pH 8–9.5, stronger zeta potential bound, low Miller index planes, and chloride exclusion
A pharmaceutical suspension comprising pharmaceutical grade water and NaHCO3 dissolved therein, gold nanocrystals suspended in said water forming a suspension, wherein said gold nanocrystals have surfaces that do not have organic chemical constituents adhered or attached to said surfaces, have a mode particle size of less than about 50 nm, are present in said pharmaceutical suspension at a concentration of at least 2-200 ppm (w/v), are shaped and comprising at least one low Miller index crystal plane selected from the group of crystal planes consisting of {111}, {110} and {100}; and said pharmaceutical suspension having a pH of between about 8 to about 9.5, said gold nanocrystals have a zeta potential of about -30 mV or lower at a temperature of about 25° C., said zeta potential being determined by measuring the electrophoretic mobility of the gold nanocrystals in the pharmaceutical suspension, and the pharmaceutical suspension does not contain chloride ions.
Across the independent claims, the coverage is directed to a pharmaceutical suspension that uses sodium bicarbonate (NaHCO3) as a processing enhancer in pharmaceutical grade water and contains gold nanocrystals with no adhered or attached organic chemical constituents, strict particle-size and concentration constraints, and defined suspension pH with zeta potential determined from electrophoretic mobility at about 25° C. In shaped embodiments, the claims further require low Miller index crystal planes, including {111}, {110}, and {100}, and corresponding shape features such as triangle and pentagon, with at least some independent coverage expressly excluding chloride ions.
Stated Advantages
Supports gold nanocrystals substantially free of organic impurities and films.
Uses inorganic processing enhancers, especially NaHCO3, to facilitate crystal growth while avoiding reductants, surfactants, and organic impurities on the final nanocrystal surface.
Inhibits macrophage migration inhibitory factor (MIF) and IL-6 but not IL-10.
Provides potency, toxicity, and onset advantages versus Auranofin.
Produces gold nanocrystals in a liquid using an adjustable plasma with controlled electrical and physical conditions.
Controls crystal shape distributions and low index crystal planes such as {111}, {100}, and {110} via applied field and ionic species.
Documented Applications
Pharmaceutical compositions using the gold nanocrystals with systemic and topical routes of administration.
Treatment-related use by inhibiting MIF in inflammatory and chronic inflammatory conditions, autoimmune conditions, hypersensitivity, and cancer, including CIA and EAE models.
Implantable device/elution concepts.
Production of gold nanocrystals or nanoparticle suspensions or colloids in a plasma-liquid system for characterization using TEM, DLS, AAS, and plasma emission or irradiance spectroscopy.
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