Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-11-06
2001-07-17
Jarvis, William R. A. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S289000
Reexamination Certificate
active
06262063
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to compositions and methods for treating tinnitus. Tinnitus can be described as “ringing” and other head noises that are perceived in the absence of any external noise source. It is estimated that 1 out of every 5 people experience some degree of tinnitus.
Tinnitus can be classified into two forms: objective and subjective. Objective tinnitus, the rarer form, consists of head noises audible to other people in addition to the sufferer. The noises are usually caused by vascular anomalies, repetitive muscle contractions, or inner ear structural defects. The sounds are heard by the sufferer and are generally external to the auditory system. This form of tinnitus means that an examiner can hear the sound heard by the sufferer by using a stethoscope. Benign causes, such as noise from TMJ, openings of the eustachian tubes, or repetitive muscle contractions may be the cause of objective tinnitus. The sufferer might hear the pulsatile flow of the carotid artery or the continuous hum of normal venous outflow through the jugular vein when in a quiet setting. It can also be an early sign of increased intra cranial pressure and is often overshadowed by other neurologic abnormalities. The sounds may arise from a turbulent flow through compressed venous structures at the base of the brain.
Subjective tinnitus may occur anywhere in the auditory system and is much less understood, with the causes being many and open to debate. Anything from the ear canal to the brain may be involved. The sounds can range from a metallic ringing, buzzing, blowing, roaring, or sometimes similar to a clanging, popping, or nonrhythmic beating. It can be accompanied by audiometric evidence of deafness which occurs in association with both conductive and sensorineural hearing loss. Other conditions and syndromes which may have tinnitus in conjunction with the condition or syndrome, are otosclerosis, Menier's syndrome, and cochlear or auditory nerve lesions. Hearing loss, hyperacusis, recruitment, FMS, and balance problems may or may not be present in conjunction with tinnitus.
Many sufferers report that their tinnitus sounds like the high-pitched background emitted by some computer monitors or television sets. Others report noises like hissing steam, running water, chirping crickets, bells, breaking glass, or even chainsaws. Some report that their tinnitus temporarily spikes in volume with sudden head motions during aerobic exercise, or with each footfall while jogging. Objective tinnitus sufferers may hear a rhythmic rushing noise caused by their own pulse. This form is known as pulsatile tinnitus.
The cause of tinnitus is largely unknown. Various conditions have been identified which are associated with it, including, allergy, diseases, such as Lyme disease, growths/tumors, general health impairments, injuries, noise exposure, syndromes, such as temporo-mandibular joint (TMJ) syndrome, and medication side-effects.
The most important treatment for tinnitus is avoidance of exposure to excessive noise, ototoxic agents, and other factors that may cause cochlear damage. Masking the tinnitus with music or through amplification of normal sounds with a hearing aid may also bring some relief. Although intravenous treatment with antiarrhythmic drugs (e.g., lidocaine) suppresses tinnitus in some individuals, evidence suggests no benefit with oral agents that are potentially suitable for long-term symptom relief. In addition, systemic procaine has been suggested. See U.S. Pat. No. 5,064,858. Among the numerous drugs that have been tried, oral antidepressants (e.g., nortriptyline at an initial dosage of 50 mg orally at bedtime) appears to be most efficacious. Thus, there remains a need for compositions and treatments for tinnitus.
DESCRIPTION OF THE INVENTION
The present invention provides compositions and methods for treating tinnitus and related disorders. In a preferred aspects of the invention, muscarinic and opioid agents are administered to patients in need of such therapy. The agents, alone, or in combination, are preferably administered topically in effective amounts, e.g., by administering a topical, otic composition to the ear.
A further aspect of the invention is to provide a pharmaceutical composition for topical use, comprising a muscarinic and/or opioid agent, and optionally biologically-active agents, such as penetration enhancers to enhance their penetration into the ear. A preferred embodiment is an otic drop dispenser comprising a topical, otic composition comprising an effective amount of a muscarinic or opioid agent and a pharmaceutically-acceptable carrier.
The compositions and methods of the present invention provide a useful way of treating, preventing, and diagnosing tinnitus. For instance, a method of the invention relates to treating tinnitus comprising, administering to the ear a topically effective amount of a muscarinic or opioid agent. By the term “treating,” it is meant that tinnitus is ameliorated, e.g., by reducing, relieving, decreasing, etc., one or more symptoms experienced by a patient with tinnitus. Symptoms that can be treated, include, e.g., ringing or other head noises, rushing noises, high-pitched squeals, ringing, bells, or any other symptoms, especially auditory, associated with the disorder. See, above for a more complete description. The therapeutic effect can be short-lived, e.g., one to four hours, or it may be longer. The therapeutic effect can be for any duration and level of relief. For example, the ringing in the ears can be temporarily completely relieved, or it may be relieved only by, e.g., 80%, 75%, 50%, 25%, or less. While the agents used herein for treating tinnitus as described as “muscarinic or opioid agent,” this is not meant to imply that these agents must accomplish their therapeutic effect by acting upon the muscarinic or opioid systems.
The composition is administered to the ear. This means that the composition is delivered to inside the ear canal, e.g., to the tympanic membrane. Delivery can be effected by any means, including drops or spray, using any effective instrument, such as an otic drop dispenser. The latter comprises a container for holding a composition in accordance with the present invention and a dropper, or other instrument for placing the composition inside the ear canal, e.g., on the tympanic membrane.
In accordance with the present invention, muscarinic agents are utilized to treat tinnitus. Preferred muscarinic agents are receptor agonists, partial agonists, mixed agonists/antagonists, and acetylcholinesterase inhibitors Preferred agonists are, e.g., acetylcholine and synthetic choline esters, and cholinomimetic alkaloids, e.g., pilocarpine, muscarine, and arecoline and their synthetic congeners, Preferred acetylcholinesterase inhibitors are, e.g., donepezil, tacrine (THA), pyrodostigmine, physostigmine, huperzine, carbamates, thiaphysovenine, phenserine, endrophonium, demarcarium, ambenonium, and preferably, neostigmine. As mentioned previously, there is no requirement that any of the above-mentioned agents operate by acting as a muscurinic agent. Thus, for example, neostigmine is useful in accordance with the present invention, irrespective of whether its effective activity is result of acetylcholinesterase inhibition. Likewise, for any agent mentioned in accordance with the present invention.
Other inhibitors which can be used in accordance with the present invention, include, e.g., those inhibitors described in U.S. Pat. No. 5,378,723, U.S. Pat. No. 5,171,750, U.S. Pat. No. 5,591,864, U.S. Pat. No. 5,455,245, U.S. Pat. No. 886,007 and chapters 7 and 8 of Goodman and Gilman,
The Pharmacological Basis of Therapeutics
, 9
th
ed., McGraw Hill, New York (1996). Pharmaceutically acceptable salts, prodrugs and derivatives of any of the above-mentioned agents can be utilized, as well.
In accordance with the present invention, opioid agents are utilized to treat tinnitus. These agents can act on one or more opiate receptors, such as mu, delta, and kappa, to which morphine, the enkepha
Jarvis William R. A.
Kim Vickie
Millen White Zelano & Branigan P.C.
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