Methods and compositions for preventing and treating auditory dysfunctions
Inventors
Assignees
US Department of Veterans Affairs
Publication Number
US-10987333-B2
Publication Date
2021-04-27
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 in a subject in need of treatment by administering 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, to treat auditory impairments. Additionally, it includes administering compositions comprising an active agent such as alkaloids, pentacyclic alkaloids, tannins, or phytochemicals derived from the inner bark or root of Uncaria tomentosa or derivatives thereof, to treat auditory impairments.
The problem solved by the invention arises from ongoing challenges in otology and audiology related to auditory dysfunctions, which are caused by acute and chronic exposure to loud sounds, ototoxic chemicals, aging, and other risk factors. Existing treatments like hearing aids and cochlear implants have limitations, such as inability to improve speech intelligibility or requiring invasive surgery. There remains a need to protect auditory cells before injury and to preserve or promote function of existing cells after injury. The invention addresses this long felt need by providing methods and compositions that inhibit cochlear inflammation, inhibit loss or death of auditory system cells, maintain or promote growth of auditory system cells, and inhibit or reverse ion dyshomeostasis, mitochondriopathy, energy catastrophe, and proliferation of free radicals in the auditory system.
The invention also provides pharmaceutical formulations comprising the active agents mentioned above with pharmaceutically acceptable carriers or excipients, formulated for various routes of administration including auricular, oral, parenteral, intraperitoneal, local, buccal, nasal, and topical routes. The disclosed agents are effective in augmenting DNA repair, providing antioxidant protection, anti-inflammation, and immunomodulation, thereby contributing to the prevention and treatment of auditory dysfunctions like hearing loss, tinnitus, hyperacusis, and related auditory processing disorders.
Claims Coverage
The patent contains two independent claims focused on methods of treating hearing loss or auditory impairment by administering a composition derived from Uncaria tomentosa bark, particularly an aqueous extract containing carboxyl alkyl esters.
Method of treating hearing loss or deafness with an aqueous extract of Uncaria tomentosa bark
This method comprises administering to a subject an effective amount of a composition comprising an aqueous extract derived from Uncaria tomentosa bark to treat hearing loss or deafness. The composition may include one or more carboxyl alkyl esters such as 3,4-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, 3-O-feruloylquinic acid, 3-O-caffeoylquinic acid, or their pharmaceutically acceptable salts. The composition can be formulated for various administration routes, including auricular, oral, parenteral, intraperitoneal, local, buccal, nasal, and topical forms, in the form of liquids, tablets, or capsules.
Method of treating auditory impairment caused by damage to the auditory system with an aqueous extract of Uncaria tomentosa bark
This method comprises administering to a subject an effective amount of a composition comprising an aqueous extract derived from Uncaria tomentosa bark to treat auditory impairment effected by an insult damaging the auditory system. The aqueous extract contains one or more carboxyl alkyl esters as specified in the claim. The composition is suitable for various administration routes and dosage forms similar to the first inventive feature.
The independent claims cover methods of treating hearing loss and auditory impairments by administering compositions comprising aqueous extracts of Uncaria tomentosa bark, particularly those containing specific carboxyl alkyl esters. The claims emphasize effective treatment using these extracts and their formulations for multiple routes and forms of delivery, addressing auditory dysfunction caused by various insults.
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 following noise injury.
Compositions reduce outer hair cell loss and preserve auditory neural sensitivity after noise exposure.
Administration of the active agents provides multifunctional cytoprotective effects including antioxidant protection, augmentation of DNA repair, anti-inflammation and immunomodulation.
The agents inhibit or reverse multiple pathological cascades underlying auditory dysfunction such as ion dyshomeostasis, mitochondriopathy, energy catastrophe and proliferation of free radicals.
Documented Applications
Preventing and treating auditory dysfunctions including hearing loss, tinnitus, hyperacusis, loudness recruitment, diplacusis, and related auditory processing disorders.
Treatment of permanent sensorineural hearing loss caused by noise exposure, ototoxic chemicals, aging, or other insults damaging the auditory system.
Use as nutraceuticals or pharmaceutical compositions for maintaining or promoting growth and viability of auditory system cells.
Use in combination therapy with other auditory therapies or ototoxic drug regimens to protect auditory function.
Treatment in various mammals including humans, non-human primates, and other animals susceptible to auditory dysfunction.
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