Functionalized nanoceria composition for ophthalmic treatment

• US 8,795,737 B2
• Filed: 12/21/2012
• Issued: 08/05/2014
• Est. Priority Date: 04/27/2006
• Status: Active Grant

• Current Assignee: University of Central Florida Research Foundation Inc. (State University System of Florida)
• Original Assignee: University of Central Florida Research Foundation Inc. (State University System of Florida)
• Inventors: Seal, Sudipta, Patil, Swanand D., Haldar, Manas K., Malik, Sanku
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): SAMALA, JAGADISHWAR RAO
• Application Number:
  US13/724,750
• Publication Number:
  US 20130123515A1
• Time in Patent Office: 592 Days
• Field of Search: 424/410, 424/421, 424/427, 424/429, 424/617, 549/210
• US Class Current: 424/617
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/244 Lanthanides; Compounds thereof medicinal preparations containing radioactive lanthanides for use in therapy or testing in vivo A61K51/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07F 5/003 without C-Metal linkages

Abstract

The invention provides a composition comprising a plurality of nanoceria particles, a sufficient amount of at least one inhibitor of human carbonic anhydrase II associated with said plurality of nanoceria particles, and a pharmaceutically acceptable carrier containing said plurality of nanoceria particles with associated inhibitor. One preferred inhibitor of human carbonic anhydrase II comprises 4-carboxybenzene sulfonamide. The disclosed composition is useful in treatment of glaucoma.

Claims

1. A method of making nanoceria particles functionalized with a human carbonic anhydrase II inhibitor, the method comprising:

(a) preparing amine functionalized cerium oxide nanoparticles by (i) reacting cerium oxide and epichlorohydrin in an aqueous sodium hydroxide solution to form a cerium oxide nanoparticle reaction product, (ii) removing the cerium oxide nanoparticle reaction product from the aqueous sodium hydroxide solution, and (iii) placing the removed cerium oxide nanoparticle reaction product into an ammonium hydroxide solution;

(b) attaching the human carbonic anhydrase II inhibitor to the amine functionalized cerium oxide nanoparticles by (i) adding NMP and BOP to a solution of the human carbonic anhydrase II inhibitor to form a reaction mixture, (ii) mixing the amine functionalized cerium oxide nanoparticles with the reaction mixture, and (iii) separating nanoceria particles functionalized with the human carbonic anhydrase II inhibitor.

2. A method of making fluorescent nanoceria particles functionalized with a human carbonic anhydrase II inhibitor, the method comprising:

(a) preparing amine functionalized cerium oxide nanoparticles by (i) reacting cerium oxide and epichlorohydrin in an aqueous sodium hydroxide solution to form a cerium oxide nanoparticle reaction product, (ii) removing the cerium oxide nanoparticle reaction product from the aqueous sodium hydroxide solution, and (iii) placing the removed cerium oxide nanoparticle reaction product into an ammonium hydroxide solution;

(b) attaching carboxyfluorescein to the amine functionalized cerium oxide nanoparticles by (i) adding NMP and BOP to a solution of carboxyfluorescein to form a first reaction mixture, (ii) mixing the amine functionalized cerium oxide nanoparticles with the first reaction mixture, and (iii) separating nanoceria particles functionalized with carboxyfluorescein; and

(c) attaching the human carbonic anhydrase II inhibitor to the nanoceria particles functionalized with carboxyfluorescein by (i) adding NMP and BOP to a solution of the human carbonic anhydrase II inhibitor to form a second reaction mixture, (ii) mixing the nanoceria particles functionalized with carboxyfluorescein with the second reaction mixture, and (iii) separating nanoceria particles functionalized with carboxyfluorescein and the human carbonic anhydrase II inhibitor.