U.S. patent application number 10/045235 was filed with the patent office on 2002-05-23 for device and method for the cessation of smoking.
This patent application is currently assigned to Addiction Therapies, Inc.. Invention is credited to Fox, Barbara S..
Application Number | 20020059939 10/045235 |
Document ID | / |
Family ID | 22926878 |
Filed Date | 2002-05-23 |
United States Patent
Application |
20020059939 |
Kind Code |
A1 |
Fox, Barbara S. |
May 23, 2002 |
Device and method for the cessation of smoking
Abstract
The present invention is directed to an oral nicotine delivery
device and a method of using the device to reduce the incidence of
tobacco smoking in a person. The device comprises a tubular chamber
having a first end suitable for taking in liquid or gas from an
external source and a second end suitable for the application of
oral suction. The chamber contains nicotine and a retainer for
preventing release of the nicotine from the first end of the
chamber. The device delivers nicotine in non-irritating solution
form.
Inventors: |
Fox, Barbara S.; (Wayland,
MA) |
Correspondence
Address: |
HALE AND DORR, LLP
60 STATE STREET
BOSTON
MA
02109
|
Assignee: |
Addiction Therapies, Inc.
Wayland
MA
|
Family ID: |
22926878 |
Appl. No.: |
10/045235 |
Filed: |
October 29, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60245490 |
Nov 3, 2000 |
|
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|
Current U.S.
Class: |
131/271 ;
131/270 |
Current CPC
Class: |
A24B 15/167 20161101;
A24F 42/60 20200101; A24F 42/20 20200101; A47G 21/183 20130101;
A61P 25/34 20180101; A61J 15/0011 20130101; A61M 15/06 20130101;
A61J 7/0038 20130101 |
Class at
Publication: |
131/271 ;
131/270 |
International
Class: |
A24F 047/00 |
Claims
What is claimed is:
1. An oral nicotine delivery device comprising: (a) a tubular
chamber having a first end suitable for taking in a liquid from an
external source and a second end suitable for oral application of
suction; (b) a nicotine granulate contained within the tubular
chamber; and (c) a retainer in the tubular chamber for preventing
release of the nicotine granulate and liquid from the first end of
the chamber, wherein the liquid enters the chamber from the
external source through the first end of the chamber, and then the
liquid and the nicotine are delivered through the second end of the
chamber, when oral suction is applied to the second end of the
chamber.
2. The device of claim 1, wherein the tubular chamber approximates
the size and shape of a conventional cigarette.
3. The device of claim 1, wherein the tubular chamber approximates
the size and shape of a conventional drinking straw.
4. The device of claim 1, wherein the retainer is fixed proximal to
the first end of the chamber.
5. The device of claim 1, wherein the retainer is transportable
toward the second end of the chamber with the nicotine granulate
and the liquid when suction is applied to the second end of the
chamber.
6. The device of claim 1, wherein the nicotine granulate comprises
coated particles of powdered nicotine.
7. The device of claim 6, wherein the nicotine particles are coated
to enhance palatability.
8. The device of claim 1, wherein the nicotine granulate comprises
particles of powdered nicotine, the particles incorporated in
spheres comprising at least one material selected from the group
consisting of sugar, starch, acacia, sodium alginate, carbomer,
cellulose, dextrotes, ethyl cellulose, methyl cellulose, and
povidone.
9. The device of claim 1, wherein the tubular chamber contains from
about 4 milligrams to about 12 milligrams of nicotine.
10. The device of claim 1, wherein a solution of nicotine is formed
when the liquid enters the chamber and contacts the nicotine.
11. The device of claim 10, wherein the solution is a
suspension.
12. The device of claim 1, wherein the nicotine is selected from
the group consisting of levo nicotine, dextro nicotine, racemic
mixtures thereof, and pharmaceutically acceptable salts
thereof.
13. A method for reducing the incidence of tobacco smoking by a
person, comprising orally administering nicotine to the person,
using an oral nicotine delivery device, the device comprising: (a)
a tubular chamber having a first end suitable for taking in a
liquid from an external source and a second end suitable for oral
application of suction; (b) a nicotine granulate contained within
the tubular chamber; and (c) a retainer in the tubular chamber for
preventing release of the nicotine granulate or liquid from the
first end of the chamber, oral administration comprising
application of oral suction by the person to the second end of the
chamber, wherein the liquid enters the chamber from the external
source through the first end of the chamber, and then the liquid
and the nicotine are delivered through the second end of the
chamber into the mouth of the person.
14. The method of claim 13, wherein a single dose of nicotine
administered to the person is from about 4 milligrams to about 12
milligrams of nicotine.
15. The method of claim 13, wherein the total daily dose of
nicotine administered to the person is from about 4 milligrams to
about 144 milligrams of nicotine.
16. The method of claim 13, wherein the blood level of nicotine in
the person after administration of the nicotine is at least about 5
nanograms of nicotine per 1 milliliter of blood.
17. The method of claim 16, wherein the blood level of nicotine in
the person after administration of the nicotine is from about 10
nanograms to about 50 nanograms of nicotine per 1 milliliter of
blood.
18. The method of claim 13, wherein a solution of nicotine is
formed when the liquid enters the chamber and contacts the
nicotine.
19. The method of claim 18, wherein the solution has an acidic
pH.
20. An oral nicotine delivery device comprising: (a) a tubular
chamber having a first end suitable for taking in a liquid or a gas
from an external source and a second end suitable for oral
application of suction; (b) a nicotine solution contained within
the tubular chamber; and (c) a retainer in the tubular chamber for
preventing release of the nicotine solution from the first end of
the chamber, wherein the nicotine solution is delivered through the
second end of the chamber when oral suction is applied to the
second end of the chamber.
21. The device of claim 20, wherein a liquid enters the chamber
from an external source through the first end of the chamber, and
then the liquid and the nicotine solution are delivered through the
second end of the chamber, when oral suction is applied to the
second end of the chamber.
22. The device of claim 20, wherein a gas enters the chamber from
an external source through the first end of the chamber, and then
the nicotine solution is delivered through the second end of the
chamber, when oral suction is applied to the second end of the
chamber.
23. The device of claim 20, wherein the tubular chamber
approximates the size and shape of a conventional cigarette.
24. The device of claim 20, wherein the tubular chamber
approximates the size and shape of a conventional drinking
straw.
25. The device of claim 20, wherein the retainer is transportable
toward the second end of the chamber with the nicotine solution
when suction is applied to the second end of the chamber.
26. The device of claim 20, wherein the nicotine solution is a
nicotine suspension.
27. The device of claim 26, wherein the nicotine suspension
comprises a nicotine granulate.
28. The device of claim 27, wherein the nicotine granulate
comprises coated particles of powdered nicotine.
29. The device of claim 28, wherein the nicotine particles are
coated to enhance palatability.
30. The device of claim 27, wherein the nicotine granulate
comprises particles of powdered nicotine, the particles
incorporated in spheres comprising at least one material selected
from the group consisting of sugar, starch, acacia, sodium
alginate, carbomer, cellulose, dextrotes, ethyl cellulose, methyl
cellulose, and povidone.
31. The device of claim 20, wherein the nicotine solution has an
acidic pH.
32. The device of claim 20, wherein the nicotine solution contains
from about 4 milligrams to about 12 milligrams of nicotine.
33. The device of claim 20, wherein the chamber contains from about
1 milliliter to about 5 milliliters of the nicotine solution.
34. The device of claim 20, wherein the nicotine in the nicotine
solution is selected from the group consisting of levo nicotine,
dextro nicotine, racemic mixtures thereof, and pharmaceutically
acceptable salts thereof.
35. The device of claim 20, wherein the nicotine solution further
comprises a flavoring.
36. A method for reducing the incidence of tobacco smoking by a
person, comprising orally administering nicotine to the person
using an oral nicotine delivery device, the device comprising: (a)
a tubular chamber having a first end suitable for taking in a
liquid or a gas from an external source and a second end suitable
for oral application of suction; (b) a nicotine solution contained
within the tubular chamber; and (c) a retainer in the tubular
chamber for preventing release of the nicotine solution from the
first end of the chamber, oral administration comprising
application of oral suction by the person to the second end of the
chamber, wherein the nicotine solution is delivered through the
second end of the chamber into the mouth of the person.
37. The method of claim 36, wherein a single dose of nicotine
administered to the person is from about 4 milligram to about 12
milligrams of nicotine.
38. The method of claim 36, wherein the total daily dose of
nicotine administered to the person is from about 4 milligrams to
about 144 milligrams of nicotine.
39. The method of claim 36, wherein the blood level of nicotine in
the person after administration of the nicotine solution is at
least about 5 nanograms of nicotine per 1 milliliter of blood.
40. The method of claim 39, wherein the peak blood level of
nicotine in the person after administration of the nicotine
solution is from about 10 nanograms to about 50 nanograms of
nicotine per 1 milliliter of blood.
41. The method of claim 36, wherein the nicotine solution is a
nicotine suspension.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The field of the present invention is pharmacology. More
specifically, the invention relates to smoking cessation methods
and aids that provide a non-irritating form of nicotine to the user
as well as the oral and tactile stimulation of smoking.
[0003] 2. Summary of the Related Art
[0004] Cigarette smoking is the leading cause of preventable
disease and death in the United States. Each year, over 400,000
adults die from tobacco-related diseases (A Report of the Surgeon
General, Rockville, Md.: Public Health Service (2000)). In addition
to health risks facing smokers themselves, the annoyance and risks
of second-hand smoke are receiving increased attention. Although
airlines, workplaces, and restaurants often ban smoking, almost 88%
of non-smokers have detectable blood levels of nicotine metabolites
(Morbidity and Mortality Weekly, Nov. 5, 1999). Environmental
tobacco smoke remains a preventable health hazard for smokers'
co-workers and family members (A Report of the Surgeon General,
Rockville, Md.: Public Health Service (2000)).
[0005] Unfortunately, 48 million adults in the United States, 24.7%
of the population, continue to smoke. Despite public health
initiatives, smoking prevalence among adults has not changed
significantly throughout the 1990's (Morbidity and Mortality
Weekly, Nov. 5, 1999). Although most smokers in the United States
wish to stop smoking, and over one third of them attempt to give up
smoking each year, only about 2.5% succeed (A Report of the Surgeon
General, Rockville, Md.: Public Health Service (2000)).
[0006] Various techniques have been advanced to aid smoking
cessation. The five major pharmacotherapies for treating tobacco
dependence are nicotine gum (see, e.g., U.S. Pat. No. 3,845,217);
nicotine transdermal patch (see, e.g., U.S. Pat. No. 4,915,950);
nicotine nasal spray (see, e.g., AU 664 41); nicotine inhaler (see,
e.g., U.S. Pat. Nos. 4,920,989 and 4,953,572); and
sustained-release bupropion hydrochloride (see, e.g., Jorenby et
al., N. Engl. J. Med., 340:685-91(1999)). Other examples of smoking
cessation aids include nicotine nose drops (see, e.g., U.S. Pat.
No. 4,579,858); nicotine lozenges (see, e.g., U.S. Pat. Nos.
4,806,35 and 5,549,906); smoke-free cigarettes (see, e.g., U.S.
Pat. Nos. 4,284,089, 4,676,259, 4,736,755, 4,813,437, 5,284,163,
and 6,041,789); compositions comprising nicotine metabolites (see,
e.g. U.S. Pat. No. 5,869,505); and drinkable nicotine solutions
(see, e.g., WO 99/55371).
[0007] Studies have shown that smokers using nicotine gum, patch,
nasal spray, inhaled nicotine, or nicotine sublingual tablets are
about 1.5 to 2 times more likely to stop smoking than smokers using
no cessation aid, and evidence suggests that bupropion may be even
more effective (see, Silagy et al., Cochrane Database Syst. Rev.,
No. 2, p.CD000146 (2000)). However, each of the existing smoking
cessation aids has drawbacks, and none has proven fully
effective.
[0008] For example, nicotine gum and lozenges can cause high
localized nicotine concentration in the mouth, which tastes
unappealing, and the gum may be difficult to chew. In addition,
chewing gum or eating lozenges may appear unprofessional. Nicotine
patches may irritate the skin, and some smokers are dissatisfied
with the lack of rapid nicotine absorption from the patch. Nicotine
nasal sprays may irritate the nose and throat. More importantly,
none of these smoking cessation aids simulates the tactile
sensations or hand-to-mouth behaviors that form an integral part of
the smoker's addiction.
[0009] Studies have shown that sensory aspects affect smoking
behavior and cigarette cravings as much as nicotine intake does.
Indeed, smokers attempting to give up cigarettes have complained
that, aside from experiencing nicotine withdrawal, they miss the
sensations and hand-to-mouth behaviors associated with smoking
(see, Rose, Ann. Rev. Med., 47:493-507 (1996)). In a study prepared
for the American Lung Association, 41% of smokers reported that
their most recent attempt to stop smoking was unsuccessful because
they missed having something to hold or to do with their hands
(Smoking Cessation Study, Yankelovich Partners, Jul. 27, 1998).
Cigarette smoking involves a hand-to-mouth ritual that may be
repeated over 70,000 times per year. Since smoking cessation
requires giving up a highly ingrained habitual motion as well as
giving up nicotine, an effective smoking cessation aid should
address the behavioral components of smoking as well as providing
nicotine replacement therapy. A smoking cessation aid should give
the smoker the comfort of an oral and tactile ritual, while at the
same time supplying nicotine. However, a smoking cessation device
that is too similar to a conventional cigarette and provides oral
sensations and tactile stimuli that too closely mimic tobacco
smoking may not be ideal. A smoker using such a device might find
it too easy to relapse into cigarette smoking (see, e.g., Schneider
et al., Addiction, 91:1293-1306 (1996)). Thus, a smoking cessation
aid that provides the synergistic combination of nicotine plus oral
and tactile stimuli, while not too closely approximating a
conventional tobacco cigarette, seems most desirable.
[0010] Among the existing smoking cessation aids, patches provide
no oral or tactile stimulus, gum, lozenges, and drinkable solutions
stimulate only the mouth, and nasal sprays stimulate only the
airways. These aids lack the important synergistic combination of
nicotine, oral stimulation, and hand-to-mouth behaviors that
smokers desire.
[0011] Some existing smoking cessation aids, such as nicotine
inhalers and various smoke-free cigarettes, do provide nicotine as
well as some behavioral aspects of smoking. However, these products
have major drawbacks. For example, U.S. Pat. No. 4,953,572 (Rose et
al.) discloses a nicotine aerosol spray designed to simulate the
sensations of inhaling tobacco smoke. The spray may be administered
through inhalation from a hand-held nebulizer. However, the
nicotine dose of the spray, which is limited by the volatility of
the inhaler's nicotine base at room temperature, is low compared to
that of tobacco smoke, and thus may be insufficient for many
smokers. Additionally, such a spray may irritate the oral
cavity.
[0012] U.S. Pat. No. 5,284,163 (Knudsen et al.) discloses a
smoke-free cigarette substitute comprising a nicotine granulate in
a tubular sleeve. The end of the sleeve contains a gum plug, which
is bitten off and held in the mouth as chewing gum. When a person
draws on the cigarette, nicotine granulate is pulled into the mouth
and can be chewed into the gum, thus dispensing nicotine into the
oral cavity. This product may possess the drawbacks of nicotine
chewing gum described above. Also, as with any smoke-free
cigarette, using it may approximate the behavioral aspects of
smoking so closely that smoking cessation becomes more
difficult.
[0013] U.S. Pat. Nos. 4,284,089 and 4,813,437 (Ray) disclose
non-pyrolytic devices shaped like ordinary cigarettes and
containing porous polymer plugs holding volatile liquid nicotine.
Drawing on the device delivers nicotine vapors to a person's lungs.
However, these devices are unable to deliver sufficient uniform
doses of nicotine. Additionally, the vaporizable nicotine tastes
unpleasant and is unstable, such that the devices have a very short
shelf life.
[0014] U.S. Pat. No. 6,041,789 (Bankert et al.) addresses some of
these problems with a non-pyrolytic cigarette substitute that
delivers a nicotine-simulating vapor mixture with a cigarette-like
taste and aroma. Instead of vaporizable nicotine, the device
contains a volatile nicotinomimetic agonist and volatile
palatability enhancing agents. However, this device does not
actually deliver nicotine. Additionally, the cigarette-like
structure, taste, and aroma may make the device so similar to a
conventional cigarette that smokers using it as a cessation aid are
likely to relapse.
[0015] Japanese Patent No. 02190178 (Akimichi et al.) discloses a
smoke-free tobacco "perfume solution" that may be vaporized and
administered through a "tubular flexible casing." However, the
solution may present health risks due to the carcinogens and
irritating particulates contained in tobacco. Additionally, as with
other smoke-free cigarettes, using the device may approximate the
actual tastes, smells, and motions of cigarette smoking so closely
that smoking cessation is made more difficult.
[0016] U.S. Pat. No. 5,293,883 (Edwards) discloses a non-pyrolytic
cigarette containing two tobacco-filled chambers, which house
unburned and pre-burned tobacco, and a mouth filter that holds
nicotine-filled ampules that release pure liquid nicotine into a
person's mouth when the person breaks them open by biting or
manually crushing the mouth filter. This device provides nicotine
and a cigarette-like taste, but it may suffer from the drawbacks of
liquid nicotine described above. Additionally, as discussed above,
the device presents the health hazards of tobacco and may make
smoking cessation more difficult by too closely approximating
actual tobacco cigarettes.
[0017] Thus, a continuing need exists for new and improved smoking
cessation aids to help reduce the ongoing public health hazards
associated with cigarette smoking and second-hand smoke.
Particularly needed is a smoking cessation aid that synergistically
provides an easily controllable nicotine dose in a non-irritating
form along with a delivery device that supplies the oral and
tactile stimulation that smokers crave, without too closely
approximating actual cigarette smoking.
SUMMARY OF THE INVENTION
[0018] The present invention solves the foregoing problems by
providing a smoking cessation aid that delivers nicotine in
non-irritating solution form and offers the oral and tactile
stimulation that smokers crave. Drawing a nicotine solution through
the device and into the mouth is similar to the accustomed
hand-to-mouth behavior of smoking. However, because the nicotine is
delivered as a solution rather than as inhaled vapors, using the
present smoking cessation aid is different enough from actual
smoking that behavioral similarities should not encourage smokers
to relapse. Nicotine delivered as a solution also does not irritate
the oral cavity as do inhaled vapors from a nicotine spray.
[0019] Accordingly, in one aspect, the invention provides an oral
nicotine delivery device comprising a tubular chamber, a nicotine
granulate contained within the chamber, and a retainer in the
chamber. The chamber has a first end suitable for taking in a
liquid from an external source and a second end suitable for oral
application of suction. The retainer prevents release of the
nicotine granulate and liquid from the first end of the chamber.
When oral suction is applied to the second end of the chamber,
liquid enters the chamber from the external source through the
first end of the chamber, and then the liquid and the nicotine are
delivered through the second end of the chamber. As used herein,
the term "comprises" means "includes, but is not limited to."
[0020] In one embodiment, the tubular chamber of the device
approximates the size and shape of a conventional cigarette. In
another embodiment, the tubular chamber approximates the size and
shape of a conventional drinking straw.
[0021] In some embodiments, the retainer is fixed proximal to the
first end of the chamber. In other embodiments, the retainer is
transportable toward the second end of the chamber with the
nicotine granulate and the liquid when suction is applied to the
second end of the chamber.
[0022] In some embodiments, the nicotine granulate comprises coated
particles of powdered nicotine. In particular embodiments, the
nicotine particles are coated to enhance palatability. In some
embodiments, the nicotine granulate comprises particles of powdered
nicotine that are incorporated in spheres comprising at least one
material selected from the group consisting of sugar, starch,
acacia, sodium alginate, carbomer, cellulose, dextrotes, ethyl
cellulose, methyl cellulose, and povidone.
[0023] In another embodiment, the tubular chamber contains from
about 1 milligram to about 40 milligrams of nicotine. In yet
another embodiment, the tubular chamber contains from about 4
milligrams to about 12 milligrams of nicotine. The nicotine is
preferably selected from the group consisting of levo nicotine,
dextro nicotine, racemic mixtures thereof, and pharmaceutically
acceptable salt forms thereof.
[0024] In some embodiments, a solution of nicotine is formed when
the liquid enters the chamber and contacts the nicotine. In
particular embodiments, the solution is a suspension.
[0025] In another aspect, the invention provides a method for
reducing the incidence of tobacco smoking by a person. The method
comprises orally administering nicotine to the person using the
device according to the previous aspect of the invention. The
person applies oral suction to the second end of the chamber, such
that the liquid enters the chamber from the external source through
the first end of the chamber. The liquid and the nicotine are then
delivered through the second end of the chamber into the mouth of
the person.
[0026] In one embodiment of the method, a single dose of nicotine
administered to the person is from about 1 milligram to about 40
milligrams of nicotine. In a particular embodiment, the dose
administered is from about 4 milligrams to about 12 milligrams of
nicotine. In a preferred embodiment, the total daily dose of
nicotine administered to the person is from about 4 milligrams to
about 144 milligrams of nicotine. In some embodiments, the blood
level of nicotine in the person after administration of the
nicotine is at least about 5 nanograms of nicotine per 1 milliliter
of blood. In some preferred embodiments, the blood level of
nicotine in the person after administration of the nicotine is from
about 10 nanograms to about 50 nanograms of nicotine per 1
milliliter of blood.
[0027] In some embodiments of the method, a solution of nicotine is
formed when the liquid enters the chamber and contacts the
nicotine. In particular embodiments, the solution has an acidic
pH.
[0028] In another aspect, the invention provides an oral nicotine
delivery device comprising a tubular chamber, a nicotine solution
contained within the chamber, and a retainer. The chamber has a
first end suitable for taking in a liquid or a gas from an external
source and a second end suitable for oral application of suction.
The retainer is for preventing release of the nicotine solution
from the first end of the chamber. The nicotine solution is
delivered through the second end of the chamber when oral suction
is applied to the second end of the chamber.
[0029] In some embodiments of the device of the invention, a liquid
enters the chamber from an external source through the first end of
the chamber when oral suction is applied to the second end of the
chamber. The liquid and the nicotine solution are then delivered
from the device through the second end of the chamber.
[0030] In other embodiments, a gas enters the chamber from an
external source through the first end of the chamber when oral
suction is applied to the second end of the chamber. The nicotine
solution is then delivered from the device through the second end
of the chamber.
[0031] In some embodiments, the tubular chamber approximates the
size and shape of a conventional cigarette. In alternative
embodiments, the tubular chamber approximates the size and shape of
a conventional drinking straw.
[0032] In some preferred embodiments, the retainer is transportable
toward the second end of the chamber with the nicotine solution
when suction is applied to the second end of the chamber.
[0033] In a particular embodiment, the nicotine solution is a
nicotine suspension. In a preferred embodiment, the nicotine
suspension comprises a nicotine granulate. In some embodiments, the
nicotine granulate comprises coated particles of powdered nicotine,
and in some preferred embodiments, the nicotine particles are
coated to enhance palatability. In some embodiments, the nicotine
granulate comprises particles of powdered nicotine that are
incorporated in spheres comprising at least one material selected
from the group consisting of sugar, starch, acacia, sodium
alginate, carbomer, cellulose, dextrotes, ethyl cellulose, methyl
cellulose, and povidone.
[0034] In a preferred embodiment, the nicotine solution contains
from about 1 milligram to about 40 milligrams of nicotine. In a
particular embodiment, the nicotine solution contains from about 4
milligrams to about 12 milligrams of nicotine. In a particular
embodiment, the chamber contains from about 1 milliliter to about 5
milliliters of the nicotine solution. The nicotine in the nicotine
solution is preferably selected from the group consisting of levo
nicotine, dextro nicotine, racemic mixtures thereof, and
pharmaceutically acceptable salts thereof. In some embodiments, the
nicotine solution has an acidic pH. In some embodiments, the
nicotine solution further comprises a flavoring.
[0035] In yet another aspect, the invention provides a method for
reducing the incidence of tobacco smoking by a person. The method
comprises orally administering nicotine to the person using the
device according to the previous aspect of the invention. The
person applies oral suction to the second end of the chamber, such
that the nicotine solution is delivered from the chamber through
the second end of the chamber into the mouth of the person.
[0036] In some preferred embodiments of this aspect of the
invention, a single dose of nicotine administered to the person is
from about 1 milligram to about 40 milligrams of nicotine. In a
particular embodiment, the single dose administered is from about 4
milligrams to about 12 milligrams of nicotine. In some preferred
embodiments, the total daily dose of nicotine administered to the
person is from about 4 milligrams to about 144 milligrams of
nicotine. In some embodiments, the blood level of nicotine in the
person after administration of the nicotine solution is at least
about 5 nanograms of nicotine per 1 milliliter of blood. In some
preferred embodiments, the blood level of nicotine in the person
after administration of the nicotine solution is from about 10
nanograms to about 50 nanograms of nicotine per 1 milliliter of
blood. In a preferred embodiment, the nicotine solution is a
nicotine suspension.
BRIEF DESCRIPTION OF THE DRAWINGS
[0037] FIG. 1 is a diagrammatic representation of a frontal view of
a nicotine delivery device of the invention that approximates the
shape and size of a conventional drinking straw.
[0038] FIG. 2 is a diagrammatic representation of a frontal view of
a nicotine delivery device of the invention that approximates the
shape and size of a conventional cigarette.
DETAILED DESCRIPTION
[0039] The issued U.S. patents, published patent applications, and
references that are cited herein are hereby incorporated by
reference to the same extent as if each were specifically and
individually indicated to be incorporated by reference. Any
inconsistency between these publications and the present disclosure
shall be resolved in favor of the present disclosure.
[0040] The present invention provides smoking cessation methods and
smoking cessation aids that deliver a nicotine solution through a
tubular device to a user. The advantage of delivering nicotine
through a tubular device is that the oral and tactile sensations
experienced by the user approximate the ingrained hand-to-mouth
behaviors associated with smoking. Thus, the device of the present
invention offers the smoker oral and manual focus, which helps to
alleviate cigarette cravings by providing an object for the smoker
to manipulate and chew.
[0041] As shown in FIG. 1, the device of the invention may
approximate a conventional drinking straw in size and shape.
Alternatively, as shown in FIG. 2, the device may approximate a
conventional cigarette in size and shape. The term "approximate"
means that the device comprises an elongated tubular chamber 10,
with a first end 12 adapted for drawing in air or liquid from an
external source and a second end 14 adapted for the application of
oral suction, and that the dimensions of the device are similar to
the dimensions of a conventional drinking straw or a conventional
cigarette. In some preferred embodiments, as shown in FIG. 1, the
device approximates a conventional drinking straw in shape and
size. The chamber 10 is preferably from about 13 to about 20
centimeters long, with a diameter of from about 4 to about 8
millimeters. More preferably, the chamber 10 is from about 15 to
about 17 centimeters long, with a diameter of from about 6 to about
7 millimeters. Alternatively, as shown in FIG. 2, the device
approximates a conventional cigarette in shape and size. In these
embodiments, the chamber 10 is preferably from about 7 to about 11
centimeters long, with a diameter of from about 7 to about 10
millimeters. More preferably, the chamber 10 is from about 8 to
about 10 centimeters long, with a diameter of about 8 millimeters.
Examples of the tubular delivery devices of the present invention
include, without limitation, devices such as those disclosed in
U.S. Pat. No. 5,718,681 (Manning) and U.S. Pat. Nos. 5,780,058,
5,985,324, 5,989,590, 6,024,721, and 6,106,845 (Wong et al.).
[0042] Materials for making the tubular chamber 10 of the present
invention may include, without limitation, paper, plastic such as
propylene/styrene copolymers, polypropylene, high density
polyethylene, low density polyethylene, ethylene vinyl acetate
copolymer, and the like.
[0043] The tubular chamber 10 of the device of the present
invention contains nicotine 16 that will be delivered to the user.
The nicotine 16 may be in any useful form, such as levo nicotine,
dextro nicotine, or a racemic mixture thereof. Pharmaceutically
acceptable salt forms of nicotine are also suitable for use in the
present invention. Nonlimiting examples of such suitable salt forms
of nicotine include the dihydrochloride, sulfate, bitartrate,
salicylate, hydrogen tartrate, and hemisulfate salts. Nicotine and
its salt forms are commercially available, for example, from
Sigma-Aldrich, St. Louis, Mo.
[0044] Preferably, the nicotine 16 is a granulate. The term
"granulate" means that the nicotine is in the form of a particulate
such as grains or beads. The size of the grains or beads preferably
is small enough not to be felt as separate particles in the mouth,
preferably less than about 200 micrometers in diameter.
[0045] In some preferred embodiments, the nicotine granulate
comprises particles of powdered nicotine which have been coated
according to standard techniques known in the art (see, e.g.,
Deasy, Crit Rev. Ther. Drug Carrier Systems, 8:39-89 (1991)). The
term "powdered" means composed of fine particles. Glatt Air
Technique (Ramsay, N.J.) and Particle and Coating Technologies,
Inc. (St. Louis, Mo.) provide particle coating services. Suitable
coatings include, without limitation, hydroxy propyl cellulose,
sugar, starch, polymer, resin, gum, wax, and fat. The diameter of
the nicotine particles before coating is preferably less than about
200 micrometers, more preferably from about 20 to about 100
micrometers, and still more preferably from about 40 to about 60
micrometers.
[0046] In some preferred embodiments, the nicotine granulate
comprises particles of powdered nicotine that are incorporated into
microspheres, which may be coated as described above. Suitable
materials for the microspheres include, without limitation, sugar,
starch, acacia, sodium alginate, carbomer, cellulose, dextrotes,
ethyl cellulose, methyl cellulose, povidone, and mixtures thereof.
For example, the microspheres may comprise a degradable
composition. The microspheres have a diameter of between about 300
micrometers and about 1000 micrometers, preferably between about
500 micrometers and about 600 micrometers. U.S. Pat. No. 5,939,100
(Albrechtson et al.) discloses further examples of nicotine
microspheres.
[0047] The coating on the nicotine particles or microspheres
preferably is designed to mask the taste of the nicotine, and thus
enhance palatability. Most preferably, the coating is formulated
such that most, but not all, of the nicotine taste is masked. The
advantage of such a formulation is that enough of the nicotine
taste is masked that the nicotine particles are palatable, but
enough nicotine taste remains that the user is aware that nicotine
is being ingested. Thus, in some preferred embodiments, the
formulation may comprise both coated and uncoated particles. The
coating on the particles or microspheres also may be designed to
achieve other functions, including, but not limited to, preventing
clumping and preventing water absorption.
[0048] Preferably, a single dose of nicotine 16 from the device of
the present invention contains a therapeutically effective amount
of nicotine. The term "single dose" means the quantity of nicotine
16 provided in the chamber 10 and delivered to the user upon
application of oral suction to the second end 14 of the chamber 10.
The term "therapeutically effective amount" means an amount
sufficient to reduce a smoker's need for nicotine from burnt
tobacco. This amount can be determined by the user's physician. An
advantage of the smoking cessation devices of the invention is
their ability to deliver a large dose of nicotine when necessary,
or a smaller dose of nicotine when appropriate. Preferably, from
about 1 milligram to about 40 milligrams of nicotine are provided
by the device. Useful amounts include from about 1 milligram to
about 5 milligrams, from about 4 milligrams to about 12 milligrams,
from about 4 milligrams to about 20 milligrams, from about 5
milligrams to about 15 milligrams, from about 5 milligrams to about
20 milligrams, and from about 20 milligrams to about 40 milligrams
of nicotine provided by the device in a single dose. A smoker
attempting to stop smoking may use the device of the present
invention from about 1 to about 12 times per day, preferably from
about 5 to about 12 times per day, such that a total daily dose of
from about 1 milligram to about 480 milligrams, preferably from
about 5 milligrams to about 480 milligrams, of nicotine is
delivered, depending on perceived need. Useful total daily doses
include from about 1 milligram to about 60 milligrams, from about 4
milligrams to about 144 milligrams, from about 4 milligrams to
about 240 milligrams, from about 5 milligrams to about 180
milligrams, from about 5 milligrams to about 240 milligrams, and
from about 240 milligrams to about 480 milligrams of nicotine. The
term "total daily dose" means the quantity of nicotine delivered to
the user during a 24-hour period.
[0049] Such a dosing regimen preferably provides a blood level of
nicotine of at least about 5 nanograms of nicotine per milliliter
of blood, with a maximum peak of about 60 nanograms of nicotine per
milliliter of blood. Preferably, the blood level of nicotine in the
user of the device is from about 10 nanograms to about 50 nanograms
of nicotine per milliliter of blood. More preferably, the user's
blood level of nicotine is about 20 nanograms of nicotine per
milliliter of blood.
[0050] Blood levels of nicotine preferably may be measured by gas
chromatography with nitrogen phosphorous detection as described,
for example, by Jacob et al., J. Chromatography, 222: 61-70 (1981).
The dosing frequency may be adjusted so as to achieve a steady
state concentration of nicotine in the blood. The steady state
blood levels of nicotine preferably fall within the preferred blood
level ranges described above. The quantities of nicotine described
above are sufficient to deliver a therapeutically effective amount
of nicotine into the user's metabolism, even after first-pass
absorption by the liver. It will be understood by those skilled in
the art that the preferred doses and blood levels of nicotine will
vary according to the preferences, metabolism, and former smoking
habits of the individual user of the smoking cessation aid of the
present invention.
[0051] In one device encompassed by the present invention, the
nicotine granulate is delivered to the user as a nicotine solution.
The term "solution," as used herein, refers to a liquid into which
the nicotine is dissolved, or a suspension or emulsion of nicotine
in a liquid. Delivery of nicotine as a solution provides several
advantages. Swallowing the solution provides the oral stimulation
that smokers crave. However, the solution does not irritate the
oral cavity as does nicotine gum. Additionally, nicotine in
solution form is absorbed in the body more slowly than nicotine
from a nasal spray. Such slow absorption allows for less frequent
dosing and provides less potential for abuse. Finally, delivery of
liquid along with the nicotine prevents high local concentrations
of nicotine, which may result in cramping, for example, when a
nicotine capsule is swallowed.
[0052] In some devices, the first end 12 of the chamber 10 is
placed in contact with an external source of liquid and the user
applies oral suction to the second end 14 of the chamber 10.
According to one method of the invention, a liquid is drawn into
the first end 12 of the chamber 10 from the external source. The
liquid then forms a suspension of the nicotine 16 granulate as it
is drawn through the chamber 10, and the suspension is delivered
through the second end 14 of the chamber 10 into the user's mouth.
Some or all of the nicotine 16 granulate also may dissolve in the
liquid, such that the nicotine 16 is delivered as a solution. WO
99/55371 (Westman et al.) discloses non-limiting nicotine solutions
whose properties may be desirable for use with the present
invention.
[0053] The external source of liquid to be drawn into the tubular
chamber 10 of a device of the invention is preferably a beverage.
Most preferably, the beverage contains a flavoring, which helps to
make the nicotine solution palatable. This is less crucial where
the nicotine taste has already been masked by coating the particles
of the nicotine granulate. The term "palatable" means that the
taste of the solution is tolerable to the user. The beverage may
comprise, but is not limited to, coffee, soda, sugar, fruit juice,
carbonation, or ethyl alcohol, such as wine, beer, or hard liquor.
Preferably, the beverage does not contain solids such as pulp. To
be palatable, the nicotine solution preferably has an acidic pH.
The term "acidic pH" means a pH of less than about 6.9. More
preferably, the nicotine solution has a pH of less than about 5.5.
Most preferably, the nicotine solution has a pH from about 2.0 to
about 4.0. Flavorings such as coffee, alcohol, and fruit juice may
be used to regulate the pH of the nicotine solution. For example,
lime juice, cranberry juice, grapefruit juice, orange juice, tonic
water, soda, and wine have pH's from about 2.0 to about 4.0, and
beer, seltzer water, coffee, and have pH's less than about 6.9.
[0054] An advantage of the smoking cessation devices of the present
invention is their compatibility with beverages that are acidic, as
the majority of popular beverages are. Existing smoking cessation
devices, such as nicotine gum and nicotine inhalers, may not be
used in combination with acidic beverages because an alkaline
environment is required for buccal absorption of the nicotine
delivered by such devices. Acidic beverages must be avoided for a
period of about one hour surrounding each use of a smoking
cessation device relying on buccal absorption of nicotine. Thus,
smokers attempting to use such devices to give up smoking must also
avoid consuming a majority of beverages much of the time. In
contrast, smokers using nicotine delivery devices of the invention,
through which nicotine is orally ingested, may consume acidic
beverages whenever they choose.
[0055] The tubular chamber 10 of the device of the present
invention may comprise two or more lumens. The multiple lumens
provide a plurality of smaller cross-sectional flow paths, which
help to optimize the flow velocity and flow volume of the liquid
from the external source, thus assuring rapid, uniform, and
complete delivery of the nicotine 16 contained within the chamber
10. The nicotine 16 may be contained in one of the lumens, or in
multiple lumens. The multiple lumens may be of identical size or of
different sizes.
[0056] Alternatively, the chamber 10 of the device of the present
invention contains a pre-formulated solution of nicotine 16 such
as, for example, a nicotine suspension. About 1 milliliter to about
40 milliliters of nicotine solution may be provided in the chamber.
Preferably, from about 1 milliliter to about 10 milliliters, most
preferably from about 1 milliliter to about 5 milliliters, of
solution are provided. The preferred single doses of nicotine,
total daily doses of nicotine, and nicotine blood levels are as
described above for the nicotine granulate.
[0057] In another method of the invention, the user applies oral
suction to the second end 14 of the chamber 10 of the device, such
that a gas such as air is drawn through the first end 12 of the
chamber 10 into the device. As the air is drawn into the chamber
10, the nicotine 16 solution contained in the chamber 10 is
delivered through the second end 14 of the chamber 10 into the
user's mouth.
[0058] Alternatively, the user places the first end 12 of the
chamber 10 in contact with an external source of a liquid and
applies oral suction to the second end 14 of the chamber 10, such
that the liquid is drawn into the first end 12 of the chamber 10
from the external source. As the liquid is drawn through the
chamber 10, it is mixed with the solution of nicotine 16 contained
in the chamber 10, and the mixture is delivered through the second
end 14 of the chamber 10 into the user's mouth. The external source
of liquid is preferably a beverage, as described above for the
device in which the chamber 10 contains a nicotine 16 granulate.
Most preferably, the beverage comprises flavorings and pH ranges as
described above.
[0059] The nicotine 16 solution contained within the chamber 10 may
itself contain the flavorings described above. Preferably, the
solution is pre-formulated to fall within the aforementioned pH
levels through use of an acid such as, for example, carbonic acid,
citric acid, acetic acid, tartaric acid, maleic acid, ascorbic
acid, adipic acid, or combinations thereof. Such pre-formulation to
optimize flavoring and pH is especially desirable if the user will
be drawing air, rather than liquid, through the first end of the
chamber, such that the nicotine 16 solution contained in the
chamber 10 is delivered without any liquid from an external source
that might enhance palatability.
[0060] The chamber 10 of the device of the present invention
further contains a retainer 18 for preventing release of nicotine
16 from the first end 12 of the chamber 10. The term "retainer"
refers to a disc, float, plug, or other restriction that blocks the
diameter of the chamber 10 such that the nicotine 16 contained
within the chamber 10 cannot be released from the first end 12 of
the chamber 10. The retainer 18 allows gas or liquid from an
external source to enter the first end 12 of the chamber 10, but
prevents release of nicotine 16 from the first end 12 of the
chamber 10. The retainer 18 also discourages release from the first
end 12 of the chamber 10 of liquid drawn into the chamber 10 from
an external source or contained within the chamber 10 as part of a
pre-formulated solution of nicotine 16.
[0061] The retainer 18 may be fixed proximal to the first end 12 of
the chamber 10. "Proximal to" the first end 12 of the chamber 10
means toward or at the first end 12 of the chamber 10.
Alternatively, the retainer 18 may be transportable toward the
second end 14 of the chamber 10. For example, the retainer 18 is
transported toward the second end 14 of the chamber 10 as the user
applies oral suction to the second end 14 of the chamber 10. Gas or
liquid from an external source is drawn through the first end 12 of
the chamber 10 into the device, and the nicotine 16 solution in the
chamber 10 is delivered into the user's mouth. As it is drawn
toward the second end 14 of the chamber 10 behind the nicotine 16
solution, the transportable retainer 18 assures that all of the
nicotine 16 in the chamber 10 is cleanly delivered through the
second end 14 of the chamber 10 into the user's mouth. The second
end 14 of the chamber 10 is constructed such that the retainer 18
itself is blocked from entering the user's mouth. For example, the
diameter at the second end 14 of the chamber 10 may be smaller than
the diameter elsewhere in the chamber 10 and smaller than the
diameter of the retainer 18, such that the retainer 18 may pass
from the first end 12 of the chamber 10 to the second end 14 of the
chamber 10, but cannot pass through the second end 14 of the
chamber 10 into the user's mouth. The diameter at the second end 14
of the chamber 10 may be made smaller than the diameter elsewhere
in the chamber 10 by a crimping of the chamber 10, a series of
dimples in the circumference of the chamber 10, or a continuous
indentation in the circumference of the chamber 10 at the second
end 14 of the chamber 10. A transportable retainer 18 is
particularly useful when the device is prefilled with liquid, i.e.,
contains a pre-formulated solution of nicotine 16.
[0062] The retainer 18 may comprise a restriction and a plug. The
term "restriction" means that the diameter near the first end 12 of
the chamber 10 is smaller than the diameter elsewhere in the
chamber 10 and smaller than the diameter of the plug, such that the
plug is contained within the chamber 10 and prevents release of
nicotine 16 through the first end 12 of the chamber 10. The
restriction may result from, for example, a crimping of the chamber
10, a series of dimples in the circumference of the chamber 10, or
a continuous indentation in the circumference of the chamber 10
near the first end 12 of the chamber 10.
[0063] The retainer 18 may alternatively comprise a particle
barrier with apertures or slits that allow liquid to pass through
the barrier when oral suction is applied to the second end 14 of
the chamber 10. A cap may be placed over the first end 12 of the
chamber 10 prior to use to avoid any possible loss of nicotine 16
or entry of contaminants through the particle barrier apertures or
slits. The apertures must be small enough that nicotine 16 cannot
pass through them and be released from the first end 12 of the
chamber 10. The slits are easier to manufacture and seal the
chamber 10 more completely prior to use than the apertures do.
Alternatively, the barrier is made from a material such as fine
mesh or porous paper that will retain the nicotine 16 in the
chamber 10 but requires no barrier apertures or slits to allow
liquid to be drawn into the chamber 10. For ease in construction,
the barrier is preferably cone-shaped and located all the way at
the first end 12 of the chamber 10.
[0064] Alternatively, the retainer 18 comprises a one-way plug or
valve. The plug or valve seals the first end 12 of the chamber 10
at atmospheric pressure. However, when suction is applied to the
second end 14 of the chamber 10, the plug is deformed and permits
liquid from an external source to flow around the plug and into the
chamber 10 through the first end 12 of the chamber 10. The plug
preferably has a density of less than one, such that it is drawn
toward the second end 14 of the chamber 10 when suction is applied
to the second end 14 of the chamber 10 and the nicotine 16
contained within the chamber 10 is delivered into the mouth of the
user. When suction is removed from the second end 14 of the chamber
10, the plug relaxes, seals the chamber 10, and remains stationary.
Transportation of the plug all the way to the second end 14 of the
chamber 10 indicates that the entire dose of nicotine 16 contained
within the chamber 10 has been delivered.
[0065] The retainer 18 alternatively comprises a cylindrical body
with at least one protrusion on its exterior surface. Liquid from
an external source is drawn through or around the retainer 18 and
into the chamber 10, but the protrusions prevent nicotine 16
solution from leaking through or around the sides of the retainer
18 and out of the first end 12 of the chamber 10. The protrusions
are fins, ridges, or rings which act as a seal for the chamber 10
and also create friction or drag between the retainer 18 and the
chamber 10, which allows time for the liquid from the external
source to mix with the nicotine 16 after passing through or around
the retainer 18.
[0066] The retainer 18 of the present invention may be made from,
for example, thermoplastic materials or low or high density foam
materials such as, without limitation, ethylene vinyl acetate
copolymers, polyolefins such as polyethylene, polypropylene, and
the like, or closed cell foam. Alternatively, the retainer 18 may
comprise, for example, a compressible plug of bonded fibers. The
fibers may be polymeric fibers, such as polyolefin fibers with or
without a polyester core, polyester, cellulose acetate, nylon,
felt, or cotton. The uncompressed fiber plug preferably has a
diameter slightly larger than the diameter of the chamber 10. Thus,
after insertion in the chamber 10, the plug seals and prevents the
release of nicotine 16 from the chamber 10, but still allows liquid
to be drawn into the chamber 10 when oral suction is applied to the
second end 14 of the chamber 10.
[0067] In some embodiments, the chamber 10 of the device of the
present invention preferably also contains a removable end cap 20
or seal located at the second end 14 of the chamber 10. The
removable end cap 20 or seal prevents the nicotine 16 granulate or
pre-formulated nicotine 16 solution contained within the chamber 10
from being released through the second end 14 of the chamber 10
during shipping and storage of the device. Before using the device,
the user removes the end cap 20 or seal from the second end 14 of
the chamber 10 so that the nicotine 16 granulate or pre-formulated
nicotine 16 solution contained within the chamber 10 may be
delivered through the second end 14 of the chamber 10 into the
user's mouth. Materials for making the end cap 20 or seal of the
present invention may include, without limitation, paper, foil,
plastic such as propylene/styrene copolymers, polypropylene, high
density polyethylene, low density polyethylene, ethylene vinyl
acetate copolymer, and the like.
[0068] In some instances, the device, itself, may comprise a
flavoring, such that it tastes pleasant for chewing as, before, or
after the nicotine dose has been delivered. The flavoring may be,
for example, sugar, cinnamon, spearmint, peppermint, wintergreen,
bubble gum, fruit, chocolate, anise, nut, coffee, tobacco, or
combinations thereof. Preferably, the flavoring is selected from
the group consisting of spearmint, peppermint, wintergreen, and
cinnamon.
[0069] The device as described in detail above provides the novel
synergistic combination of oral and tactile stimulation along with
a controlled dose of nicotine in non-irritating solution form.
Smokers attempting to stop smoking may use the device as an aid
that can satisfy nicotine needs and at the same time prevent
cigarette cravings by providing a substitute for the hand-to-mouth
behavioral component of smoking. The synergistic combination of the
present invention provides an important new method for reducing the
incidence of tobacco smoking in smokers who appreciate the health
risks of smoking and wish to stop.
[0070] The following nonlimiting examples further illustrate
certain preferred embodiments of the present invention:
EXAMPLE 1
[0071] Safety and Pharmacokinetics Study
[0072] 1. Device
[0073] Nicotine is administered orally using a straw-like smoking
cessation device of the invention as shown in FIG. 1. The chamber
10 is a plastic drinking straw. The retainer 18 is a filter at the
first end 12 of the straw. The user places the first end 12 of the
device in a glass of apple juice and applies oral suction to the
second end 14 of the device, such that the juice and nicotine 16
are delivered into the user's mouth.
[0074] The nicotine 16 in the device is in the form of coated sugar
spheres of nicotine bitartrate having a diameter of approximately
500 micrometers. The nicotine spheres are prepared by spraying
nicotine bitartrate dihydrate with a binder onto sugar spheres and
applying a film coating. Using a Wurster processing unit, particles
are suspended in air using a controlled airflow system and a
coating suspension is added at a controlled rate via a
pneumatically atomized nozzle. As atomized droplets of the coating
solution contact the particles, they spread and coalesce on the
particle surface. Excess moisture from the applied liquid
evaporates in the apparatus, leaving a coated dry substance. Mixing
of the coating suspension occurs throughout the manufacturing
process to ensure uniformity of the suspension.
[0075] 2. Administration
[0076] On day one, following overnight abstinence from smoking,
healthy adult smokers who wish to give up smoking receive a single
dose of nicotine or placebo. Smokers are assigned to each dosage
group in a double blind, randomized manner, as is well known in the
art. The following data are collected before dosing, every thirty
minutes for the first two hours after dosing, and every hour for
the following six hours: plasma levels of nicotine and cotinine,
vital signs, adverse events, and patient's assessment of cigarette
cravings. Baseline and endpoint clinical chemistry, hematology,
urinalysis, and ECG are also monitored.
[0077] On day eight, again following overnight abstinence from
smoking, the same subjects receive the same dose of nicotine or
placebo. The dose is repeated periodically throughout the day. The
following data are collected as described above before the first
dosing and one hour after each dose is administered: plasma levels
of nicotine and cotinine, vital signs, adverse events, and
patient's assessment of cigarette cravings. Baseline and endpoint
clinical chemistry, hematology, urinalysis, and ECG are also
monitored. The data are used to evaluate the safety and
pharmacokinetics of nicotine delivery by the smoking cessation
device.
EXAMPLE 2
[0078] Efficacy Study
[0079] In a double blind study, three hundred healthy adult smokers
who wish to give up smoking use the smoking cessation device as
described in Example 1 to deliver nicotine or placebo over a ten
week period. Each device contains 5-10 mg of nicotine or placebo.
Subjects are instructed to use the device as needed for smoking
urges, but not to exceed 12 doses per day. Patients are
concurrently enrolled in a counseling program to provide behavioral
support for smoking cessation. Smoking abstinence data are
collected during the last eight weeks of treatment, serving as the
primary endpoint. Abstinence is defined as four weeks of continuous
abstinence from smoking during the study period. Subjects have
weekly clinic visits for monitoring plasma levels of nicotine and
cotinine, vital signs, adverse events, and patient's assessment of
cigarette cravings. Baseline and endpoint clinical chemistry,
hematology, urinalysis, and ECG are also monitored.
[0080] EQUIVALENTS
[0081] While the foregoing invention has been described in some
detail for purposes of clarity and understanding, it will be
appreciated by one skilled in the art from a reading of this
disclosure that various changes in form and detail can be made
without departing from the scope of the invention and the attached
claims.
* * * * *