Gold-based nanocrystals for medical treatments and electrochemical manufacturing processes therefor

• US 10,449,217 B2
• Filed: 03/21/2017
• Issued: 10/22/2019
• Est. Priority Date: 07/08/2009
• Status: Active Grant

• Current Assignee: Clene Nanomedicine, Inc.
• Original Assignee: Clene Nanomedicine, Inc.
• Inventors: Mortenson, Mark Gordon, Pierce, D. Kyle, Bryce, David A., Wilcox, Reed N., Lockett, Anthony, Merzliakov, Mikhail
• Primary Examiner(s): Fisher, Melissa L
• Application Number:
  US15/465,092
• Publication Number:
  US 20170348350A1
• Time in Patent Office: 945 Days
• Field of Search: None
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/242 Gold; Compounds thereof
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 29/02 : without antiinflammatory effect
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/06 : for tuberculosis
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: B22F 1/0545 : Dispersions or suspensions of nanosized particles
• CPC Class Codes: B22F 1/0553 : Complex form nanoparticles, e.g. prism, pyramid, octahedron
• CPC Class Codes: B22F 9/00 : Making metallic powder or suspensions thereof
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C30B 29/02 : Elements
• CPC Class Codes: C30B 29/60 : characterised by shape
• CPC Class Codes: C30B 7/12 : by electrolysis
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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).

Claims

1. A suspension comprising:

a.) water;

b.) at least one processing enhancer comprising at least one material selected from the group consisting of sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, trisodium phosphate, disodium phosphate, monosodium phosphate, and potassium phosphates;

c.) gold nanocrystals suspended in said water forming a suspension, wherein said gold nanocrystals;

i.) having surfaces that do not have organic chemical constituents adhered or attached to said surfaces;

ii.) having a mode particle size of less than about 50 nm;

iii.) are present in said suspension at a concentration of at least 2 ppm by weight per volume; and

d.) said suspension having a pH of between about 5 to about 9.5, said 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.

2. The suspension of claim 1, wherein said gold nanocrystals have a zeta potential of about −

30 mV or lower.

3. The suspension of claim 1, wherein said gold nanocrystals have a zeta potential of about −

40 mV or lower.

4. The suspension of claim 1, wherein said gold nanocrystals have a zeta potential of about −

50 mV or lower.

5. The suspension of claim 1, wherein said gold nanocrystals have shapes comprising faces with spatially extended low index crystal planes, said shapes appearing as triangles and pentagons.

6. The suspension of claim 5, wherein said shaped gold nanocrystals further comprise shapes which appear as hexagons and diamond shapes.

7. The suspension of claim 1, wherein said gold nanocrystals are present at a concentration of about 2-200 ppm by weight per volume.

22. The suspension of claim 1, wherein said pH is between about 8 and about 9.5, said mode particle size is within a range of about 8-18 nm, and said zeta potential is about −

40 mV or lower.

23. The suspension of claim 6, wherein said pH is between about 8 and about 9.5, said mode particle size is within a range of about 8-18 nm, and said zeta potential is about −

40 mV or lower.

24. The suspension of claim 7, wherein said pH is between about 8 and about 9.5, said mode particle size is within a range of about 8-18 nm, and said zeta potential is about −

40 mV or lower.

25. The suspension of claim 4, wherein said gold nanocrystals comprise shapes comprising low Miller index crystal planes, said shapes appearing as triangles and pentagons.

26. The suspension of claim 7, wherein said pH is between about 8 and about 9.5, said mode particle size is within a range of about 8-18 nm, and said zeta potential is about −

40 mV or lower.

27. The suspension of claim 3, wherein said gold nanocrystals are shaped and comprising at least one low Miller index {111} crystal plane.

28. The suspension of claim 1, wherein said gold nanocrystals are shaped and include least one low Miller index crystal plane selected from the group of crystal planes consisting of {111}, {110} and {100}.

29. The suspension of claim 1, wherein said gold nanocrystals are shaped and comprising at least one low Miller index {111} crystal plane.

30. The suspension of claim 1, wherein said gold nanocrystals have a mode particle size of less than about 30 nm.

31. The suspension of claim 1, wherein said gold nanocrystals have a mode particle size within a range of about 8-18 nm.

8. A composition comprising:

a.) a suspension medium comprising 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

b.) shaped gold nanocrystals in said suspension medium forming a suspension, said 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;

i.) having surfaces that do not have organic chemical constituents adhered or attached to said surfaces;

ii.) having a mode particle size of less than about 50 nm;

iii.) are present in said suspension at a concentration of at least about 2 ppm by weight per volume; and

iv.) having shapes comprising low Miller index crystal planes.

9. The suspension of claim 8, wherein said shaped gold nanocrystals having a zeta potential of about −

40 mV or lower.

10. The suspension of claim 8, wherein said mode particle size is within a range of about 8-18 nm and said pH is between 8 to about 9.5.

11. The suspension of claim 10, wherein said shaped gold nanocrystals having said low Miller index crystal planes comprising triangle and pentagon shapes.

12. The suspension of claim 11, wherein said shaped gold nanocrystals having said low Miller index crystal planes further comprise hexagon and diamond shapes.

13. A suspension comprising:

a.) a suspension medium comprising water and sodium bicarbonate dissolved therein, said suspension medium having a pH of between about 5 to about 9.5;

b.) shaped gold nanocrystals in said suspension medium forming a suspension, said 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;

i.) having surfaces that do not have organic chemical constituents adhered or attached to said surfaces;

ii.) having a mode particle size of less than about 30 nm;

iii.) are present in said suspension at a concentration of at least about 2 ppm by weight per volume; and

iv.) comprise triangle and pentagon shapes.

14. The suspension of claim 13, wherein said shaped gold nanocrystals have a zeta potential of about −

40 mV or lower.

15. The suspension of claim 13, wherein said shaped gold nanocrystals having a mode particle size within a range of about 8-18 nm.

16. The suspension of claim 13, wherein said shaped gold nanocrystals having a mode particle size of less than about 21 nm and having a zeta potential of about −

40 mV or lower.

17. The suspension of claim 13, wherein said shaped gold nanocrystals further comprising hexagon and diamond shapes.

18. The suspension of claim 13, wherein said suspension does not contain chloride ions.

19. The suspension of claim 13, wherein said shaped gold nanocrystals are present in said suspension at a concentration of about 2-200 ppm.

20. The suspension of claim 13, wherein said shaped gold nanocrystals having a mode particle size within a range of about 8-18 nm and the suspension has a pH of between about 8 to about 9.5.

21. The suspension of claim 13, wherein said pH is between about 8 and about 9.5, said mode particle size is within a range of about 8-18 nm, and said zeta potential is about −

40 mV or lower.

32. A composition comprising:

a.) water and NaHCO₃ dissolved therein,

b.) gold nanocrystals suspended in said water forming a suspension, wherein said gold nanocrystals;

i.) having surfaces that do not have organic chemical constituents adhered or attached to said surfaces;

ii.) having a mode particle size of less than about 50 nm;

iii.) are present in said suspension at a concentration of at least 2 ppm (w/v);

iv.) 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

c.) said 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 suspension, and the suspension does not contain chloride ions.

33. The suspension of claim 32, wherein said gold nanocrystals have shapes comprising faces with spatially extended low index crystal planes, said shapes appearing as triangles and pentagons when dried from suspension on a surface.

34. The suspension of claim 33, wherein said shaped gold nanocrystals further comprise hexagon and diamond shapes.

35. The suspension of claim 32, wherein said at least one low Miller index crystal plane comprises a crystal plane {111}.

36. [Newly Added] A suspension comprising:

a.) water;

b.) at least one processing enhancer comprising potassium bicarbonate;

c.) gold nanocrystals suspended in said water forming a suspension, wherein said gold nanocrystals;

i.) having surfaces that do not have organic chemical constituents adhered or attached to said surfaces;

ii.) having a mode particle size of less than about 50 nm;

iii.) are present in said suspension at a concentration of at least 2 ppm by weight per volume; and

d.) said suspension having a pH of between about 5 to about 9.5, said 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.