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Assignees
Member
Oklahoma Medical Research FoundationFounded in 1946, this independent nonprofit biomedical research institute conducts basic, translational, and clinical research in critical areas such as heart disease, cancer, autoimmune, and neurodegenerative diseases. Its mission focuses on understanding biological mechanisms and advancing diagnostics and therapeutics. Activities include conducting clinical trials, managing a patent portfolio, commercializing biotechnologies, and supporting the biotech community. Research efforts are funded by grants and philanthropy, and the institute hosts advanced facilities, interdisciplinary research teams, and collaborations with academia and industry.
Founded in 1946, this independent nonprofit biomedical research institute conducts basic, translational, and clinical research in critical areas such as heart disease, cancer, autoimmune, and neurodegenerative diseases. Its mission focuses on understanding biological mechanisms and advancing diagnostics and therapeutics. Activities include conducting clinical trials, managing a patent portfolio, commercializing biotechnologies, and supporting the biotech community. Research efforts are funded by grants and philanthropy, and the institute hosts advanced facilities, interdisciplinary research teams, and collaborations with academia and industry.
Publication Number
US-10111843-B2
Publication Date
2018-10-30
Expiration Date
Abstract
The treatment options for treating blast-induced and noise-induced traumatic brain injury and tinnitus are limited. Thus, the current invention provides methods for treating traumatic brain injury and tinnitus. The methods involve administering a pharmaceutically effective amount of a composition comprising 2,4-disulfonyl α-phenyl tertiary butyl nitrone and N-acetylcysteine (NAC).
Core Innovation
The invention provides methods and compositions to prevent or treat noise- and blast-induced traumatic brain injury and noise-induced tinnitus using nitrones, primarily 2,4-disulfonyl α-phenyl tertiary butyl nitrone (HPN-07; 2,4-disulfonyl PBN), alone or in combination with antioxidants including N-acetylcysteine and 4-hydroxy-α-phenyl butyl nitrone with optional acetyl-L-carnitine. The invention further discloses that 2,4-disulfonyl PBN increases blood–brain barrier permeability and thereby enhances central nervous system bioavailability of co-administered agents.
The patent addresses biomarkers of noise and blast injury and synapse preservation by reporting that combinations of HPN-07 and antioxidants reduce injury markers, preserve synapses in auditory nuclei (DCN, AVCN, PVCN), hippocampus and entorhinal cortex, and lessen long-term damage, with [procedural detail omitted for safety] supporting these outcomes. The specification further describes [procedural detail omitted for safety], and adjunct antioxidants and mitochondria-targeted Szeto–Schiller peptides.
Claims Coverage
The patent includes one independent claim that discloses a two-step method. The independent claim presents two main inventive features.
Administration of 2,4-disulfonyl a-phenyl tertiary butyl nitrone to increase blood-brain barrier permeability
administering 2,4-disulfonyl a-phenyl tertiary butyl nitrone to an organism in an amount sufficient to increase blood-brain barrier permeability
Administering a compound concurrently or following nitrone administration to increase CNS bioavailability
administering the compound to the organism either concurrently or following administration of 2,4-disulfonyl a-phenyl tertiary butyl nitrone
The independent claim covers a method comprising administration of 2,4-disulfonyl a-phenyl tertiary butyl nitrone to increase blood–brain barrier permeability, combined with administration of a compound concurrently or after the nitrone to increase central nervous system bioavailability.
Stated Advantages
Prevention or treatment of noise- and blast-induced traumatic brain injury and noise-induced tinnitus
Reduction of injury markers in affected brain regions
Preservation of synapses in auditory nuclei, hippocampus and entorhinal cortex
Lessening of long-term damage following noise or blast exposure
Increase of blood–brain barrier permeability to enhance central nervous system bioavailability of co-administered agents
Documented Applications
Prevent or treat noise- and blast-induced traumatic brain injury (TBI)
Prevent or treat noise-induced tinnitus
Increase central nervous system bioavailability of co-administered compounds, including MRI contrast agents
Administration of a compound to treat a disease or condition of the brain
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