Methods and compositions for preventing and treating auditory dysfunctions
Inventors
GUTHRIE ONEIL W, null • Guthrie, O'neil W.
Assignees
US Department of Veterans Affairs
Publication Number
US-9889107-B2
Publication Date
2018-02-13
Expiration Date
2033-05-31
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The invention provides methods for treating auditory impairments in a subject in need of treatment comprising administering to said subject an effective amount of a composition comprising, as an active agent, one or more of a carboxy alkyl ester, a quinic acid derivative, a caffeic acid derivative, a ferulic acid derivative, or a quinic acid lactone or derivative thereof or pharmaceutically acceptable salt thereof and an acceptable carrier or excipient, so as to treat auditory impairments in the subject.
Core Innovation
The invention provides methods for preventing and treating auditory dysfunctions such as hearing loss, tinnitus, hyperacusis, and related auditory processing disorders by administering compositions containing active agents, including carboxy alkyl esters, quinic acid derivatives, caffeic acid derivatives, ferulic acid derivatives, quinic acid lactones or derivatives thereof, or extracts from Uncaria tomentosa. These compositions are delivered in effective amounts with acceptable carriers or excipients to treat or prevent auditory impairments in subjects in need thereof.
The invention addresses the problem of auditory dysfunction arising from acute or chronic exposures to loud sounds, ototoxic chemicals, aging, and other causes, which lead to hearing loss and related impairments including tinnitus and diminished speech understanding. Current treatments primarily involve prevention or use of hearing aids and cochlear implants, which have limitations in restoring function or preventing cell loss. There remains a need for methods to protect auditory cells before injury, preserve their function, and promote growth or repair after injury.
The invention solves this problem by providing novel therapeutic agents and methods that inhibit cochlear inflammation, prevent loss or death of auditory system cells, maintain or promote growth of such cells, augment endogenous DNA repair, and inhibit or reverse ionic dyshomeostasis, mitochondriopathy, energy catastrophe, and free radical proliferation in the auditory system. Administration of the specified compositions thus offers a multifunctional means of treating or preventing auditory dysfunction in various contexts including noise-induced, age-related, or drug-induced hearing loss.
Claims Coverage
The patent includes one independent claim focused on a method to inhibit loss or death of auditory system cells through administration of compositions comprising specified active agents.
Method of inhibiting loss or death of auditory system cells
A method of inhibiting the loss or death of the cells of the auditory system in a mammal comprising administering to said mammal an effective amount of a composition comprising, as an active agent, one or more carboxy alkyl esters or pharmaceutically acceptable salts thereof.
Prophylactic administration prior to auditory insult
Administration of the composition may be effected prior to an insult that can damage the auditory system and can be administered prophylactically over a period of days, weeks, or months to achieve therapeutic benefit.
Active agent characteristics and formulations
The active agent is characterized as having a molecular weight less than or equal to 10,000 daltons and being hydrophilic. The composition can include aqueous extracts from Uncaria tomentosa bark and may be formulated for various administration routes including auricular, oral, parenteral, intraperitoneal, local, buccal, nasal, or topical. The composition can be in liquid, tablet, or capsule form.
The claims cover therapeutic methods using compositions with carboxy alkyl esters or derivatives to inhibit auditory cell loss and hearing loss, including prophylactic administration and various formulations, highlighting the multifunctional active agents derived from Uncaria tomentosa or related compounds.
Stated Advantages
Treatment with carboxy alkyl esters of Uncaria tomentosa augments recovery of sensory and neural functions following noise injury.
The compositions facilitate almost complete recovery of outer hair cell function and reduce cell loss after noise exposure.
They provide significant protection of neural sensitivity after noise exposure.
The active agents induce antioxidant protection, augment DNA repair, inhibit cochlear inflammation, and modulate multiple pathophysiologic mechanisms underlying auditory dysfunctions.
Documented Applications
Treatment or prevention of hearing loss, tinnitus, hyperacusis, loudness recruitment, diplacusis, and related auditory processing disorders in mammals including humans and other animals.
Use as monotherapy or combination therapy with other agents including ototoxic drugs, radiation therapy, or surgery to protect auditory system function.
Prophylactic administration to subjects exposed to loud noise, ototoxic medications, or other insults known to cause auditory dysfunction.
Interested in licensing this patent?