US 12,329,780 B2
Acute and chronic mitochondrial electron transport chain dysfunction treatments and graphenic materials for use thereof
James M. Tour, Bellaire, TX (US); Lizanne Nilewski, La Jolla, CA (US); William Sikkema, Langley (CA); Kimberly Mendoza, Houston, TX (US); Thomas Andrew Kent, Houston, TX (US); William Dalmeida, Jr., League City, TX (US); Paul J. Derry, Houston, TX (US); Ah-Lim Tsai, Sugarland, TX (US); Muralidhar L. Hegde, Houston, TX (US); Prakash Dharmalingam, Houston, TX (US); Pavana Dixit Hegde, Houston, TX (US); Sankar Mitra, Houston, TX (US); and Joy Mitra, Houston, TX (US)
Assigned to William Marsh Rice University, Houston, TX (US); Board of Regents, The University of Texas System, Austin, TX (US); Baylor College of Medicine, Houston, TX (US); Houston Methodist Research Institute, Houston, TX (US); and The United States Government, Washington, DC (US)
Appl. No. 16/608,713
Filed by WILLIAM MARSH RICE UNIVERSITY, Houston, TX (US); BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM, Austin, TX (US); BAYLOR COLLEGE OF MEDICINE, Houston, TX (US); HOUSTON METHODIST RESEARCH INSTITUTE, Houston, TX (US); and THE UNITED STATES GOVERNMENT, Washington, DC (US)
PCT Filed Apr. 30, 2018, PCT No. PCT/US2018/030315
§ 371(c)(1), (2) Date Oct. 25, 2019,
PCT Pub. No. WO2018/201157, PCT Pub. Date Nov. 1, 2018.
Claims priority of provisional application 62/556,719, filed on Sep. 11, 2017.
Claims priority of provisional application 62/491,995, filed on Apr. 28, 2017.
Prior Publication US 2020/0222453 A1, Jul. 16, 2020
Int. Cl. A61K 33/36 (2006.01); A61K 9/16 (2006.01); A61K 9/51 (2006.01); A61K 33/04 (2006.01); A61K 33/24 (2019.01); A61K 33/241 (2019.01); A61K 33/26 (2006.01); A61K 33/30 (2006.01); A61K 33/34 (2006.01); A61P 25/28 (2006.01)
CPC A61K 33/36 (2013.01) [A61K 9/1641 (2013.01); A61K 9/51 (2013.01); A61K 33/04 (2013.01); A61K 33/24 (2013.01); A61K 33/241 (2019.01); A61K 33/26 (2013.01); A61K 33/30 (2013.01); A61K 33/34 (2013.01); A61P 25/28 (2018.01)] 4 Claims
OG exemplary drawing
 
1. A therapeutic composition comprising an antioxidant nanoparticle covalently modified with a chelating moiety, wherein
(a) the antioxidant nanoparticle has both antioxidant and pro-oxidant properties;
(b) the therapeutic composition is operable to act as a high capacity oxidant having an oxygen radical absorbance capacity value between 200 and 15,000 and directly transports electrons and reduces key mitochondrial enzymes when administered to a subject;
(c) the therapeutic composition has a chelation efficacy that is at least ten times greater as compared to a same amount of the chelating moiety without the antioxidant nanoparticle;
(d) the chelating moiety is a metal-chelating moiety; and
(e) the metal-chelating moiety is a chelator of a metal selected from a group consisting of aluminum, americium, arsenic, cadmium, cesium, chromium, copper, curium, iron, lead, mercury, plutonium, thallium, uranium, and zinc, wherein
(i) the chelating moiety is deferoxamine (DEF),
(ii) the antioxidant nanoparticle is selected from a group consisting of poly(ethylene glycol)-hydrophilic carbon clusters (PEG-HCCs), poly(ethylene glycol)-ylated graphene quantum dots (PEG-GQDs), and poly(ethylene glycol)-ylated perylenediimide (PEG-PDI),
(iii) the therapeutic composition is selected from a group consisting of deferoxamine poly(ethylene glycol)-hydrophilic carbon clusters (DEF-PEG-HCCs), deferoxamine poly(ethylene glycol)-ylated graphene quantum dots (DEF-PEG-GQDs), and deferoxamine poly(ethylene glycol)-ylated perylenediimide (DEF-PEG-PDI), and
(iv) ratio of poly(ethylene glycol) (PEG) to chelating moiety is between 1:3 and 3:1.