US 12,329,780 B2Granted

Acute and chronic mitochondrial electron transport chain dysfunction treatments and graphenic materials for use thereof

AssigneesWilliam Marsh Rice University, Board of Regents, The University of Texas System, Baylor College of Medicine, Houston Methodist Research Institute, The United States Government

InventorsJames M. Tour, Lizanne Nilewski, William Sikkema, Kimberly Mendoza, Thomas Andrew Kent, William Dalmeida, Jr., Paul J. Derry, Ah-Lim Tsai, Muralidhar L. Hegde, Prakash Dharmalingam, Pavana Dixit Hegde, Sankar Mitra, Joy Mitra

Life of this patent

Estimating the term…

patentgrep

Loading patent…

Abstract

Modified hydrophilic carbon clusters (HCCs), poly(ethylene glycol)-hydrophilic carbon clusters (PEG-HCCs) and similarly structured materials like graphene quantum dots (GQDs), PEGylated GQDs, small molecule antioxidants, and PEGylated small molecule antioxidants. These materials have been modified with an iron chelating moiety, deferoxamine, or a similar chelating moiety. By exploiting common binding sites, the carbon nanostructure facilitates intracellular transport including in mitochondria, reduces oxidative breakdown of the chelator moiety prior to treatment, and reduces both the cause and consequences of metal induced oxidative stress within the body thus providing a novel form of therapy for a range of oxidative and metal-related toxicities. Graphenic materials can be used for the treatment of acute and chronic mitochondrial electron transport chain dysfunction.

Claims4

Dependent claims

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.

7 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/608,713Filed 30 Apr 2018 · us provisional application
Priority: 28 Apr 2017
Published: US 2020/0222453 A116 Jul 2020
Granted: 17 Jun 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification15 codes

A61K 33/36
Heavy metals; Compounds thereof: arsenic; Compounds thereof
A61K 45/00
Medicinal preparations containing active ingredients not provided for in groups a61k31/00 -
A61K 9/14
Medicinal preparations characterised by special physical form: particulate form, e.g. powders, Processes for size reducing of pure drugs or the…
A61K 9/1641
Organic macromolecular compounds: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene…