Title:  Method of treating sleeplessness with melatonin on an acute basis

United States Patent:  6,703,412

Issued:  March 9, 2004

Inventors:  Rosenthal; Holly A. (11 Pine Glen, Blauvelt, NY 10913)

Appl. No.:  255255

Filed:  September 27, 2002

Abstract

A method of treating sleeplessness in a human comprising administering to said human suffering from said sleeplessness an effective sleep-inducing amount of not greater than about 5 mg of melatonin or a pharmaceutically acceptable salt thereof, said administration being at a point in time after said human attempts to go to sleep until no less than one hour prior to said patient's desired awakening time.

BRIEF SUMMARY OF THE INVENTION

These objects are achieved by administering melatonin in low pharmacologic doses of about 1.0 mg to about 3.0 mg to a patient suffering from sleeplessness at a time period after bedtime until at least 1 hour before the patient intends to wake up in the morning.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is a method of treating sleeplessness in a human comprising administering to said human suffering from said sleeplessness an effective sleep-inducing amount of not greater than about 5 mg of melatonin or a pharmaceutically acceptable salt thereof, said administration being at a point in time after said human attempts to go to sleep until no less than 1 hour prior to said patient's desired awakening time.

For purposes of this invention, sleeplessness is generally a condition that will be subjective to the individuals who will be taking advantage of the invention. The subject will generally attempt to go to sleep at a particular time. After some period of time (a first time period), generally of (but not limited to) at least 15 minutes, whether not falling asleep at all, or drifting in and out of a sleep state, the subject feels that he or she is not falling asleep as desired, and considers that he or she is having an episode of sleeplessness. Similarly, on awakening during the subject's ordinary sleep period (one that is ordinary or typical for the subject at hand in the subject's own estimation) and failing to be able to fall asleep again within a reasonable period of time (a second time period, again, within the subject's own subjective estimation, usually but not limited to, at least 15 minutes). In both cases, the term "suffering from sleeplessness" includes those individuals who desire to quickly fall into a state of sleep.

Generally, the time period for administration of melatonin within the present invention is from the point where one has recognized or believes that one is having an episode of sleeplessness until an amount of time (a third time period) prior to the subject's intended time for awakening. This third time period is generally, but not limited to, not less than one hour, prior to the subject's intended time for awakening. For example, the subject may take the melatonin dose at any time point earlier in the night such as at least 1.5, 2, 2.5, 3, 3.5, 4, or more hours (or any interval between those stated here) prior to the subject's desired awakening time.

The effective sleep-inducing amount of melatonin is preferably about 0.1 mg to about 10 mg, preferably at least about 0.3 mg, more preferably at least about 0.5 mg, even more preferably at least about 1 mg, still more preferably at least about 1.25 mg, most preferably at least about 1.5 mg while preferably not more than about 7.5 mg, more preferably not more than about 5 mg, more preferably not more than about 4.5 mg. A fairly typical dose for a subject would be about 1.5 mg; however, a dose of 3.0 mg, or 4.5 mg may be used as well. Each subject can determine the individual dose for himself or herself based on the subjects own personal reaction to an initial dose of melatonin in accordance with the present invention.

Melatonin is commercially available in a variety of dosage ranges, including 1.5 mg per dosage unit. However, none of the products currently available, to the present inventor's knowledge, have administration instructions that include administering melatonin after attempting to go to sleep or administering melatonin after awakening during a typical sleep period and not being able to go back to sleep.

Melatonin may be administered orally, parenterally (e.g., intracisternally, subcutaneously, intraperitoneally), rectally, transdermally, or nasally, in any suitable dosage form, including capsules, softgels, ordinary or quick dissolve tablets, powders, nasal sprays, sublingual forms, transdermal patches, etc., although instant dissolve tablets or softgels are preferred for their fast delivery of melatonin.

The dosage forms will generally have, in addition to melatonin, a suitable carrier therefore and may have additional formulation excipients generally known in the art. Furthermore, while it is preferable for there to be no other sleep-inducing agents present in the formulation, additional ingredients may be optionally present, if desired. Generally, if ingredients with sleep-inducing properties are present, they will be used in amounts which would be near the minimum or below the therapeutic level for such other active, in order to keep the product from resulting in sleepiness after awakening.

Inactive materials for formulating the melatonin into suitable dosage forms are well know in the art and include, without limitation, carriers, binders, disintegrants, processing aids, lubricants, coating materials, etc. Those of ordinary skill in the art will readily know how to formulate the melatonin into suitable dosage forms, whether alone, or together with other ingredients.

EXAMPLES

The following examples exemplify, but do not limit, the present invention.

Example 1

Melatonin 1.5 mg capsules are administered to subjects having difficulty falling asleep after one hour of trying to fall asleep at their normal bedtime. The subjects fall asleep within 20 minutes and sleep through the night. On awakening, the subjects are alert, without any decrement in faculties.

Example 2

Subjects are those who awake at about midway during their normal sleep period and once awake have trouble falling back asleep. After 15 minutes of trying to fall back asleep, the subjects are given melatonin 1.5 mg capsules. The subjects fall asleep within 20 minutes and sleep through the remainder of the night, awakening 3-4 hours later. The subjects are refreshed, and not sleepy or drowsy.

Claim 1 of 15 Claims

I claim:

1. A method of treating sleeplessness in a human comprising administering to said human suffering from said sleeplessness an effective sleep-inducing amount of not greater than about 10 mg of melatonin or a pharmaceutically acceptable salt thereof, said administration being at a point in time from (a)(i) after said human has attempted to go to sleep and has failed to go to sleep, or (ii) after said human has awakened from sleep and is unable to return to sleep until (b) no less than one hour prior to said patient's desired awakening time, said administration being while said patient is awake and desires to fall asleep.

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