Methods and compositions for preventing and treating auditory dysfunctions
Inventors
Assignees
US Department of Veterans Affairs
Publication Number
US-9457009-B2
Publication Date
2016-10-04
Expiration Date
2033-05-31
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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 treating auditory impairments, including hearing loss, tinnitus, hyperacusis, and related auditory processing disorders, by administering compositions containing one or more active agents selected from carboxy alkyl esters, quinic acid derivatives, caffeic acid derivatives, ferulic acid derivatives, quinic acid lactones or derivatives thereof, or pharmaceutically acceptable salts thereof, combined with acceptable carriers or excipients.
These methods extend to inhibiting cochlear inflammation, preventing loss or death of auditory system cells, maintaining or promoting growth of such cells, augmenting endogenous DNA repair, and inhibiting or reversing pathological processes such as ion dyshomeostasis, mitochondriopathy, energy catastrophe, and proliferation of free radicals within the auditory system.
The problem being addressed is the difficulty in preventing or treating auditory dysfunctions that arise from noise exposure, ototoxic chemicals, aging, and other causes leading to hearing loss and associated impairments. Presently, treatments are limited, with hearing aids and cochlear implants unable to restore damaged cells or improve functions such as speech intelligibility or tinnitus effectively. There is a need for means to protect auditory cells before injury and to promote repair and function after injury.
Claims Coverage
There is one independent claim covering a method of treating auditory impairment associated with cochlear outer hair cell damage, dysfunction, or loss by administering specific carboxy alkyl esters or their salts.
Use of specific carboxy alkyl esters as active agents for treating auditory impairment
The method comprises administering to a subject an effective amount of a composition containing one or more carboxy alkyl esters selected from a defined group of compounds including various dicaffeoylquinic acids, feruloylquinic acids, caffeoylquinic acids, specific hydroxypropanoyl-trihydroxycyclohexanecarboxylic acids, cis-5-O-caffeoylquinic acid, 3-O-caffeoylquinic acid lactone, 3-O-caffeoyl-4-O-feruloylquinic acid, or pharmaceutically acceptable salts thereof.
Formulation aspects of the composition
The composition may also further comprise an aqueous extract from Uncaria tomentosa bark and can be formulated for various routes of administration including auricular, oral, parenteral, intraperitoneal, local, buccal, nasal, and topical administration in forms such as liquid, tablet, or capsule.
Therapeutic applications and parameters
The treatment aims to restore cochlear outer hair cell function to treat auditory impairments including permanent sensorineural hearing loss, tinnitus, loudness recruitment, hyperacusis, diplacusis, and speech intelligibility deficits. The active agents may have molecular weights less than or equal to 10,000 daltons.
The claims define a therapeutic method using specified carboxy alkyl ester compounds and their pharmaceutically acceptable salts and formulations, including extracts from Uncaria tomentosa bark, administered in various forms and routes to restore cochlear outer hair cell function and treat auditory impairments.
Stated Advantages
The compositions and methods provide augmented recovery of sensory and neural functions following noise injury.
The active agents exhibit multifunctional cytoprotective effects including antioxidant protection, augmentation of DNA repair, anti-inflammation, and immunomodulation.
Treatment with the active agents facilitates almost complete recovery of outer hair cell function and limits cell loss after noise exposure.
The active agents protect and preserve neural sensitivity in the auditory system after damaging noise exposure.
Documented Applications
Treatment or prevention of hearing loss and other auditory dysfunctions in humans and other mammals.
Use as monotherapy or in combination with other therapeutic agents including anti-cancer therapies that may be ototoxic.
Formulation into pharmaceuticals, nutraceuticals, dietary supplements, and veterinary compositions for various administration routes including oral, parenteral, topical, and auricular.
Use in animals exposed to noise-induced auditory trauma, ototoxic drug exposure, aging-related auditory decline, and other causes of auditory dysfunction.
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