United States Patent:   5,972,974

Assignee:  Pharmaco Behavioral Associates, Inc. (Towson, MD)

Filed:  November 7, 1996

A therapeutic method is provided to manage human body weight in nicotine-experienced or nicotine-naive individuals, comprising of transdermally administering an amount of nicotine metabolites or a pharmaceutically acceptable salts thereof to a human in need of such treatment, in an amount which is effective to manage human body weight.

SUMMARY OF THE INVENTION

The present invention provides a therapeutic method of treatment to (a) alleviate tobacco withdrawal syndrome (TWS), (b) alleviate the similar abstinence effects due to cessation of nicotine alone, or (c) manage body weight in nicotine-experienced or nicotine-naive individuals comprising of administering to a human in need of such treatment, i.e., a nicotine user, abstinent nicotine user or nicotine-naive, an amount of a nicotine metabolite or a combination of nicotine metabolites (e.g., cotinine, nornicotine, norcotinine, nicotine N-oxide, cotinine N-oxide, 3-hydroxycotinine, 5-hydroxycotinine) or their pharmaceutically acceptable salts thereof, in an amount effective to significantly reduce or eliminate at least one of the symptoms of TWS or nicotine withdrawal. As discussed above, the symptoms of both tobacco and nicotine withdrawal are similar and are art recognized to include craving for tobacco, anxiety, irritability, insomnia, impatience, tension, depression, increased appetite with accompanying weight gain, restlessness, difficulty concentrating, drowsiness and decreased heart rate. The present method is effective both to alleviate TWC acutely and to permit patients to maintain abstinence from tobacco use for extended periods of time.

In a preferred embodiment, the present invention also provides a therapeutic method to alleviate the craving for cigarettes, tobacco and/or nicotine that is associated with cessation of nicotine use, e.g., by chewing or smoking, by the administration of an effective amount of a nicotine metabolite or a combination of nicotine metabolites or their pharmaceutically acceptable salts thereof, to a human in need of such treatment. However, the present invention is also useful to treat the symptoms of nicotine withdrawal which are due, for example, to cessation of use of nicotine gum or a nicotine transdermal patch. In addition, this invention should be useful in the management of human body weight in nicotine-experienced or nicotine-naive individuals.

The present invention is exemplified by a study in which a nicotine metabolite, (-)-cotinine base, was intravenously administered to abstinent cigarette smokers. The administration of the nicotine metabolite, cotinine, caused many subjective changes without affecting cardiovascular activity. While cotinine administration appeared to mildly exacerbate some of the symptoms of the tobacco withdrawal syndrome such as anxiety, tension, restlessness and insomnia, it simultaneously decreased ratings of sedation and hunger. Also, cotinine administration reduced peak craving scores for cigarettes, tobacco and/or nicotine experienced during the session.

Nicotine metabolites may have many qualities which can enhance their value as aids to smoking cessation. In particular, cotinine has a long in vivo half-life, no cardiovascular activity, complete oral bioavailability, potentially low abuse liability and has not been reported to be harmful even at very high doses in many species including man. Also, because cotinine has no significant cardiovascular effect, a combined pharmacologic replacement treatment approach using cotinine in combination with nicotine or other metabolites of nicotine may be possible. The other nicotine metabolites should have many of these same qualities, and therefore should provide relief from the aforementioned problems in a similar manner.

The present invention also provides an article of manufacture comprising packaging material, such as a box, bottle, tube, sprayer, insufflator, intravenous (i.v.) bag, envelope and the like; and at least one unit dosage form of a pharmaceutical agent contained within said packaging material, wherein said pharmaceutical agent comprises a nicotine metabolite or combination of nicotine metabolites or their pharmaceutically acceptable salts thereof in an amount effective to alleviate tobacco withdrawal syndrome, the symptoms of nicotine withdrawal or the craving associated with cessation of tobacco smoking or manage human body weight, and wherein said packaging material includes instruction means which indicate that said nicotine metabolite or combination of nicotine metabolites or said pharmaceutically acceptable salts thereof can be used for alleviating tobacco withdrawal syndrome, the symptoms of nicotine withdrawal, the craving associated with the cessation of tobacco smoking or manage human body weight. Suitable instruction means include printed labels, printed package inserts, tags, cassette tapes, and the like.

Claim 1 of 6 Claims

1. A therapeutic method used to manage short-term human body weight changes through suppression of appetite or prevention of weight gain or induction of weight loss during the initial tobacco abstinence phase in nicotine-experienced or nicotine-naive human individuals comprising of administering by means of a transdermal patch an amount of a nicotine metabolite or combination of nicotine metabolites or their pharmaceutically acceptable salts thereof to a human individual in need of such treatment, which amount is sufficient to deliver a dose of a nicotine metabolite or combination of nicotine metabolites from about 1 mg/kg to about 100 mg/kg of body weight of the human individual in need of such treatment, and is effective to suppress appetite, prevent gain or induce weight loss in a human individual in need of such treatment.

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