Method and composition for treating sleep apnea

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...

Reexamination Certificate

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C514S077000

Reexamination Certificate

active

06329352

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to a treatment for sleep apnea using natural or synthetic lung surfactant to coat the pharyngeal mucosa. The invention thereby provides therapeutic relief for a medical condition having serious adverse health effects. An apparatus is also provided for therapeutic administration of the surfactant.
BACKGROUND OF THE INVENTION
Among the most troublesome of sleep impairing ailments is persistent snoring and associated sleep apnea during which normal breathing is interrupted for a sufficient time to produce anoxia. Episodes of apnea occur with sufficient frequency that the subject is deprived of the normal benefits of restful sleep, and frequently suffers from profound daytime drowsiness, mental fatigue, and weakness. Snoring occurs in the collapsible part of the airway from the epiglottis to the choanae involving the soft palate, uvula, tonsils, tonsillar pillars, and the pharyngeal muscles and mucosa. In apnea, the air passage becomes completely occluded, interrupting breathing. Typically periods of loud snoring are punctuated with silent episodes in which the airway is occluded, followed by a loud resuscitative snort which restores breathing and partially wakes the sleeper.
Mild cases of snoring and apnea are nuisances easily tolerated, but more severe cases entail health risks that are only beginning to be studied and understood. A pathological condition exists when apnea episodes extend longer than 10 seconds and occur more than 7-10 times in an hour. When airflow is reduced to 30% of normal, hypopnea or a hypopneic episode ensues. The number of apneas and hypopneas together are taken into account when assessing the severity of the problem. The sum of apneas and hypopneas occurring in an hour is termed the apnea-hypopnea index or the respiratory disturbance index.
Sleep apnea has been associated with arterial hypertension, electrocardiographic changes and arrhythmias, and even sudden death. For a general review of the pathologies associated with sleep apnea by statistical evaluation, see
Sleep and Breathing,
ed. N. A. Saunders, 2 ed., Marcel Dekker, N.Y.: 1994. There are other correlations between brain asthma, brain infarction, and other neurological pathologies. In one Finnish study, 68% of stroke victims studied had a history of severe snoring and sleep apnea. There is a further correlation between habitual sleep apnea and arterial hypertension, another condition associated with stroke prevalence.
Cahan, et al., Chest, 1990; 98: 122s reported a significant correlation between a moderate apnea-hypopnea index (>15) and elevation in insulin levels. At index values greater than 40, fasting hyperglycemia and hyperinsulinemia were observed. Cushing's disease and acromegaly are two further diseases associated with both sleep apnea and insulin resistance, as described in Fairbanks, et al.,
Snoring and Obstructive Sleep Apnea,
2ed., Raven Press, Ltd., New York: 1994.
There have been many modes of treatment proposed for snoring and sleep apnea. Over three hundred devices and treatment methods have received patents in the U.S. Patent and Trademark Office. These include body appurtenances as disclosed, for example, in U.S. Pat. No. 1,216,679 (a snore ball designed to discourage sleeping on the back), U.S. Pat. No. 2,339,998 (a chin strap), U.S. Pat. No. 3,696,377 (a snore activated microphone), U.S. Pat. No. 3,998,209 (a snore trainer delivering an electric shock), U.S. Pat. No. 5,284,829 (a mouth held appliance), and U.S. Pat. No. 5,154,184 (adjustable snore device). One device of interest is a tongue-retaining device, which pulls the superior aspect of the tongue forward, thereby keeping the tongue away from the posterior wall of the pharynx. Most of these devices have limited value, as they only superficially address the actual anatomical bases of snoring and windpath occlusion, or create uncomfortable wearing conditions worse than the snoring and apnea.
The most successful treatment device has been the use of continuous positive airway pressure, as described in Sanders, et al., Chest, 1984; 86: 839. However, very few patients are tolerant of the device, because of the continuous presence of tubes within the mouth and pharyngeal passages. As a last resort, this approach has proven efficacious for some patients, but is often poorly tolerated and compliance may be difficult.
Surgical intervention has been utilized extensively, either by bypassing the obstructive area by tracheostomy or eliminating the obstruction by excision. The latter excision can involve removal of excessive oropharyngeal issues such as an edematous uvula, redundant mucosal folds of the pharyngeal wall, excessive tissue in the soft palate, overly large tonsils, and redundant pillar mucosa. Depending on the particular structures implicated in the airway obstruction, many surgical strategies have been developed. For a general description of such strategies, see Fujita, “Pharyngeal Surgery for Obstructive Sleep Apnea and Snoring,” in
Snoring and Obstructive Sleep Apnea,
2ed., supra. The drawbacks to surgical intervention include the usual risks of invasive procedures in addition to creating problems with swallowing, speaking, and other daytime activities without relieving the snoring and apnea. The observed anatomical defects usually do not deviate much from normal, so that the benefits of surgery are often insignificant.
Good medical practice also recommends reducing known risk factors for sleep apnea, which are sometimes completely effective for diminishing the problem to tolerable levels. These include eliminating obesity (Smith, et al.,
Ann. Int. Med.,
1985, 102: 850), curtailing alcohol consumption (Issa, et al.,
J. Neurol. Neurosurg. Psychiatry
1982, 45: 353.), avoiding certain drugs known to exacerbate the problem such as flurazepam and other benzodiazepines, and manipulating sleep position. The use of many devices noted above reflects an attempt to constrain the body in a posture which reduces or eliminates snoring and sleep apnea.
Finally, there have been efforts to reduce or eliminate snoring and sleep apnea by the administration of therapeutic agents. In several studies protriptyline, a nonsedating, tricyclic antidepressant was administered. Although some reduction in apnea episodes was noted, there was a corresponding increase in hypopneas corresponding to the shorting of REM sleep associated with apnea. In addition, side effects are observed including urinary hesitancy, impotence, rash, and ataxia. Medroxyprotesterone acetate has also been used, but without statistically significant benefit. Similarly, administration of tryptophan, a serotonin precursor, has shown little efficacy.
Some reduction in snoring utilizing phophocholinamin as a topical lubricant was noted in human subjects, as described in
Am. J. Otolaarygol.,
8: 236 (1987). U.S. Pat. No. 5,569,679 discloses topical use of methylsulfonylethane applied to nasal passages from a dispenser to relieve snoring. Widdlcombe, et al.
Eur. Respir. J.,
1:785 (1988) reported that Sonarex®, a commercial preparation of surface active agents, reduced the sound of snoring and decreased upper airway resistance in dogs. However, to date no effective drug therapy specifically for sleep apnea has been demonstrated in humans.
SUMMARY OF THE INVENTION
The relation between snoring and sleep apnea is associational but not necessarily causative. Therefore, therapies focussing on reduction in snoring may not decrease by as significant an extent episodes of hypopnea and apnea. Snoring per se, while bothersome to the sleeper and annoying to companions, is not necessarily pathological or seriously harmful. It is therefore an object of the present invention to develop a therapy for sleep apnea and hypopnea leading to significant reduction in such episodes, whether or not there is a concomitant reduction in snoring. Another object is to provide a convenient method and apparatus of using the therapy which is not invasive or distracting, or which produces serious discomfort. A still further object is to

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