Malic acid stabilized nanoceria particles

• US 10,143,661 B2
• Filed: 10/17/2014
• Issued: 12/04/2018
• Est. Priority Date: 10/17/2013
• Status: Active Grant

• Current Assignee: Cerion, LLC (Revstone Industries LLC)
• Original Assignee: Cerion, LLC (Revstone Industries LLC)
• Inventors: Sandford, David Wallace
• Primary Examiner(s): Ahmed, Hasan S
• Assistant Examiner(s): Singh, Randeep
• Application Number:
  US15/029,672
• Publication Number:
  US 20160331697A1
• Time in Patent Office: 1,509 Days
• Field of Search: None
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• 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: A61K 9/5123 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5192 Processes

Abstract

A process for making nanoparticles of biocompatible materials is described, wherein an aqueous reaction mixture comprising cerous ion, malic acid, an oxidant, and water, is provided along with temperature conditions to directly form within the reaction mixture, a stable dispersion of nanoceria particles. Biocompatible nanoparticles comprised of ceria and malic acid are described. A reduction in cell death in a murine model of ischemic stroke utilizing intact brain slices is demonstrated by a prophylactic treatment of ceria nanoparticles prepared with malic acid.

Claims

1. A process of making nanoparticles, comprising:

(a) forming a reaction mixture comprising a cerium ion, malic acid, an oxidant, and water; and

(b) forming in the reaction mixture a dispersion of nanoparticles.

2. The process according to claim 1, wherein said dispersion of nanoparticles is formed directly in the reaction mixture without isolation of the nanoparticles.

3. The process according to claim 1, further comprising the step of adjusting the pH of said reaction mixture to an alkaline condition.

4. The process according to claim 1, further comprising the step of heating or cooling said reaction mixture to a temperature in the range of about 0°

C. to about 100°

C.

5. The process according to claim 1, wherein said cerium ion comprises cerous ion.

6. The process according to claim 1, wherein said oxidant is hydrogen peroxide.

7. The process according to claim 1, wherein said nanoparticles comprise a cerium oxide phase.

8. The process according to claim 6, wherein said cerium oxide phase has a cubic fluorite structure.

9. The process according to claim 1, wherein said nanoparticles are characterized by a hydrodynamic diameter less than about 5 nanometers.

10. The process according to claim 1, further comprising the step adjusting said dispersion of nanoparticles to a pH within a suitable physiological condition.

11. The process according to claim 1, further comprising the step of administering to a patient a pharmaceutical composition comprising said dispersion of nanoparticles.

12. A nanoparticle dispersion comprising cerium oxide nanoparticles prepared according to the process of claim 1.

13. The nanoparticle dispersion of claim 12, wherein said cerium oxide nanoparticles are characterized by a cubic fluorite structure.

14. The nanoparticle dispersion of claim 12, wherein said cerium oxide nanoparticles are characterized by a hydrodynamic diameter less than about 5 nanometers.

15. A pharmaceutical composition comprising cerium oxide nanoparticles prepared according to the process of claim 1.