Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution... – Containing or obtained from nicotiana
Reexamination Certificate
2001-09-25
2003-06-24
Lankford, Jr., Leon B. (Department: 1654)
Drug, bio-affecting and body treating compositions
Plant material or plant extract of undetermined constitution...
Containing or obtained from nicotiana
C424S449000, C424S451000, C424S440000, C424S464000, C514S343000
Reexamination Certificate
active
06582737
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to pharmaceutical compositions to alleviate tobacco withdrawal syndrome. The invention further relates to a therapeutic method of alleviating tobacco withdrawal syndrome and craving associated with cessation of nicotine use in a patient who is refraining from smoking tobacco by administration of the pharmaceutical compositions. The pharmaceutical compositions and methods of alleviating tobacco withdrawal syndrome effectively alleviate the symptoms of depression which is related to the withdrawal of nicotine.
BACKGROUND OF THE INVENTION
Despite the potential adverse health effects associated with smoking, the vast majority of cigarette smokers are unable to cease smoking. The lack of success may be related to the tobacco withdrawal syndrome that most smokers experience when they attempt to cease smoking. The lack of success may be related to the tobacco withdrawal syndrome that most smokers experience when they attempt to cease smoking. Smoking withdrawal symptoms are associated with craving for cigarettes; the craving is the most difficult symptom to alleviate.
There has been a large body of research focused on the factors that precipitate craving in an attempt to understand these aspects better to be able to deal with these severe issues. It is also believed by some investigators that smokers can be divided into two categories: cravers and non-cravers. These separate populations have different responses to smoking cessation therapy. Most commercial replacement products available for nicotine smoking cessation have been lacking in dealing with the issue of satisfying craving for nicotine cigarette smoking. The most common effects are similar to those in almost all abstinence syndromes and include decreased heart rate, anxiety, tension, difficulty concentrating, impatience, depression, increased appetite with accompanying weight gain, inability and restlessness. Most withdrawal effects occur within 24 hours and peak in the first 1 to 2 weeks and significantly decrease after one month. It is widely believed that the effects of abstinence from tobacco are due to nicotine deprivation, and that abstinence from smoking prevents smokers from stopping the habit of smoking.
Of the pharmacological approaches to aiding tobacco use cessation, nicotine gum or nicotine patches are the most widely used. Nicotine gum and transdermal patches decrease abstinence discomfort. The nicotine nasal spray inhaler is also beneficial in decreasing abstinence discomfort. Bupropion has been proven to reduce agitation, anxiety, and insomnia; additionally, there are studies which indicate that bupropion will also assist in weight maintenance.
Nicotine acts as an agonist at the nicotine cholinergic receptors at the autonomic ganglia in the adrenal medulla, at neuromuscular junctions, and in the brain. Nicotine's positive reinforcing properties are believed to be the result of the release of neurotransmitter including acetylcholine, beta-endorphin, dopamine, norepinephrine, serotonin, and other compounds that mediate pleasure, arousal, elevated mood, appetite, and other desirable psychological states.
When nicotine gum is chewed, nicotine is displaced from polarities by alkaline salts. Buffering a gum to a pH of 8.5 enhances the absorption of nicotine; the rate of absorption of the oral route is slower than that from the lungs during smoking. The time to peak concentration of the nicotine gum is from 15 to 30 minutes after the start of chewing.
Bupropion acts as an antidepressant. Although the exact mechanism of the antidepressant action is unclear, it is thought to be mediated by bupropion's noradrenergic and/or dopaminenergic effects. Bupropion is a weak inhibitor of neuronal uptake of norepinephrine, serotonin, and dopamine, although inhibition of uptake occurs at higher doses than those required for bupropion's antidepressant effects.
U.S. Pat. No. 5,837,280 discloses compositions and methods for the transdermal administration of azapirones for treating a variety of treating psychogenic symptomatology, including the symptoms associated with nicotine dependence and the symptoms associated with withdrawal from tobacco. There is no mention of administration of the azapirones by any route in conjunction with transdermal administration of bupropion base.
U.S. Pat. No. 5,972,974 discloses compositions contained in a patch for transdermal administration where the transdermal patch contains nicotine or an active nicotine metabolite. The nicotine or active nicotine metabolite is transdermally administered to patients including patients who are undergoing the effects of abstinence from tobacco. There is no suggestion in this reference to administer nicotine or an active nicotine metabolite in conjunction with transdermal administration of bupropion base to alleviate tobacco-smoking withdrawal symptoms.
U.S. Pat. No. 6,004,970 discloses a method of treating a patient for nicotine dependency by administering to the patient an effective amount of naltrexone and an effective amount of nicotine. The nicotine may be administered to the patient using a nicotine patch and the naltrexone may be administered intradermally. An antidepressant such as WELBUTRIN
R
which is bupropion hydrochloride may be administered to the patient in conjunction with the nicotine and the naltrexone. Intradermal administration is mentioned as one route of administration.
It is noted that the present invention is directed to the administration of nicotine or an active nicotine metabolite in conjunction with a bupropion base the latter administered transdermally through a patch and not in conjunction with a bupropion salt such as bupropion hydrochloride. Furthermore an opioid antagonist such as naltrexone is not a part of the present invention and thus the present invention is very different from the invention disclosed in U.S. Pat. No. 6,004,970.
Hydroxybupropion, an effective metabolite of bupropion, may have clinically significant antidepressant effects.
OBJECTS OF THE INVENTION
It is an object of the invention to provide a pharmaceutical composition to assist a smoker to gradually give up the need to smoke tobacco and the need for nicotine.
It is a further object of the invention to provide relief to the patient of symptoms associated with withdrawal of smoking cigarettes, including agitation and depression.
SUMMARY OF THE INVENTION
Quitting smoking is hard. Smoking is a physical addiction as well as a habituation. The pharmaceutical composition according to the present invention is a treatment package that has been designed to assist in slowly weaning the patient, off of nicotine, while eliminating the depressive state associated with withdrawal from smoking. Because smoking is such a strong habit it is necessary to provide a well-contained therapy. The unit will assist the patient by allowing him/her to eliminate the habit of smoking over time as well as to provide relief of symptoms associated with withdrawal of smoking cigarettes.
The present invention is directed to a pharmaceutical composition in unit dosage form combining two pharmaceutically active ingredients to alleviate tobacco-smoking withdrawal symptoms which comprises:
(a) a therapeutically effective amount of nicotine, at least one active nicotine metabolite, a combination of nicotine and an active nicotine metabolite, or an azapirone, or a pharmaceutically acceptable salt thereof; and
(b) a transdermal delivery system consisting essentially of a bupropion base in a therapeutically effective amount.
Preferably the transdermal delivery system is a patch for transdermal delivery of bupropion to a mammalian subject, said patch comprising:
(i) a flexible, inert backing layer incapable of absorbing bupropion base;
(ii) a release liner through which bupropion base is not permeable; and
(iii) a reservoir located between the backing layer and the release liner, said reservoir having a bupropion-transfer surface adjacent to the release liner and adapted to contact the skin of the patient and sufficient to transfer an effective
Hirsh Mark
Junginger Hans E.
Midha Kamal K.
Coe Susan D.
Dubno Herbert
Lankford , Jr. Leon B.
Myers Jonathan
Peirce Management, LLC
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