U.S. patent application number 14/327137 was filed with the patent office on 2015-01-15 for inhalable compositions comprising caffeine, methods of use and an apparatus for using the same.
The applicant listed for this patent is Ahkeo Ventures LLC. Invention is credited to Kelly McNeal, Brent Skoda.
Application Number | 20150013695 14/327137 |
Document ID | / |
Family ID | 51261253 |
Filed Date | 2015-01-15 |
United States Patent
Application |
20150013695 |
Kind Code |
A1 |
McNeal; Kelly ; et
al. |
January 15, 2015 |
INHALABLE COMPOSITIONS COMPRISING CAFFEINE, METHODS OF USE AND AN
APPARATUS FOR USING THE SAME
Abstract
Described herein are compositions, methods and an apparatus
relating to the pulmonary delivery of an inhalable composition
comprising caffeine, or a salt thereof, and a solvent selected from
the group consisting of propylene glycol, glycerol, ethanol and a
combination thereof.
Inventors: |
McNeal; Kelly; (Irving,
TX) ; Skoda; Brent; (Irving, TX) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Ahkeo Ventures LLC |
Irving |
TX |
US |
|
|
Family ID: |
51261253 |
Appl. No.: |
14/327137 |
Filed: |
July 9, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61844772 |
Jul 10, 2013 |
|
|
|
Current U.S.
Class: |
131/328 ;
131/329; 131/359 |
Current CPC
Class: |
A24F 40/10 20200101;
A61K 45/06 20130101; A61K 47/10 20130101; A61M 15/06 20130101; A24B
15/167 20161101; A61K 31/522 20130101; A61M 11/042 20140204; A61K
9/007 20130101; A24F 47/008 20130101 |
Class at
Publication: |
131/328 ;
131/359; 131/329 |
International
Class: |
A24B 15/16 20060101
A24B015/16; A61M 11/04 20060101 A61M011/04; A61M 15/06 20060101
A61M015/06; A61K 31/522 20060101 A61K031/522; A24F 47/00 20060101
A24F047/00 |
Claims
1. An inhalable composition, comprising caffeine, or a salt
thereof, and a solvent selected from the group consisting of
propylene glycol, glycerol, ethanol and a combination thereof.
2. The inhalable composition of claim 1, wherein the composition
comprises propylene glycol and glycerol, and the composition has a
ratio of propylene glycol to glycerol of about 2:1 to about
1:2.
3. The inhalable composition of claim 1, wherein the composition is
a vapor comprising liquid droplets.
4. The inhalable composition of claim 3, wherein the liquid
droplets have an average diameter of about 1 micron to about 10
microns.
5. The inhalable composition of claim 1, wherein the composition
further comprises an additive selected from the group consisting of
yerba mate leaf extract, huperizine, taurine, inositol,
niacinamide, phenylalanine, citicoline, or a salt of any thereof,
and a combination thereof.
6. The inhalable composition of claim 5, wherein the composition
comprises: about 1 wt. % to about 10 wt % caffeine HCl, about 1 wt.
% to about 10 wt % yerba mate leaf extract, about
1.times.10.sup.-10 wt. % to about 1.times.10.sup.-5 wt %
huperizine, about 1 wt. % to about 30 wt % taurine, about 1 wt. %
to about 30 wt % inositol, about 0.1 wt. % to about 3 wt %
niacinamide, about 1 wt. % to about 30 wt % phenylalanine, about 1
wt. % to about 30 wt % citicoline, about 1 wt. % to about 30 wt %
propylene glycol, and about 1 wt. % to about 30 wt % glycerol.
7. The inhalable composition of claim 6, wherein the composition
comprises: about 3.8 wt % caffeine HCl, about 2.5 wt % yerba mate
leaf extract, about 1.times.10.sup.-8 wt % huperizine, about 9.5 wt
% taurine, about 9.5 wt % inositol, about 0.6 wt % niacinamide,
about 9.5 wt % phenylalanine, about 7.6 wt % citicoline, about 9.5
wt % propylene glycol, and about 9.5 wt % glycerol.
8. The inhalable composition of claim 6, wherein the composition
further comprises about 1 wt % to about 30 wt % of a flavorant.
9. The inhalable composition of claim 8, wherein the flavorant is
selected from the group consisting of citric acid, lemon extract,
lime extract, orange extract, cinnamon, peppermint, spearmint and a
combination thereof.
10. The inhalable composition of claim 1, wherein the composition
does not comprise methanol or ethanol.
11. The inhalable composition of claim 1, wherein the composition
has a viscosity of about 0.01 Pas to about 0.1 Pas at 20.degree.
C.
12. An apparatus for the pulmonary administration of an inhalable
composition to a subject, wherein: the apparatus is a personal
electronic vaporizer; the inhalable composition comprises caffeine,
or a salt thereof, and a water-miscible solvent selected from the
group consisting of propylene glycol, glycerol, ethanol and a
combination thereof; and the apparatus comprises a means to store
the inhalable composition as a liquid, a means to heat and
transform the liquid into a vapor and a means to administer at
least 0.0001 mg caffeine, or a salt thereof, from the vapor to the
subject per inhalation by the subject from the apparatus.
13. The apparatus of claim 12, wherein the apparatus comprises the
inhalable composition.
14. The apparatus of claim 13, wherein the composition further
comprises an additive selected from the group consisting of yerba
mate leaf extract, huperizine, taurine, inositol, niacinamide,
phenylalanine, citicoline, or a salt of any thereof, and a
combination thereof.
15. The apparatus of claim 12, wherein the transformed vapor
comprises liquid droplets having an average diameter of about 1
micron to about 10 microns.
16. The apparatus of claim 12, wherein the means to administer at
least 0.0001 mg caffeine, or a salt thereof, administers about
0.0002 mg to about 50 mg of caffeine, or a salt thereof, from the
vapor to the subject per inhalation by the subject from the
apparatus.
17. A method for administering an inhalable composition to a
subject in need thereof, the method comprising providing the
subject with: the inhalable composition comprising caffeine, or a
salt thereof, and a solvent selected from the group consisting of
propylene glycol, glycerol, ethanol and a combination thereof; and
an apparatus for the pulmonary administration of the inhalable
composition; wherein, the method results in a pulmonary
administration of at least 0.0001 mg of caffeine from the inhalable
composition to the subject.
18. The method of claim 17, wherein the composition is inhaled from
the apparatus as a vapor comprising liquid droplets.
19. The method of claim 18, wherein the vapor is formed at a
temperature of about 250.degree. F. to about 450.degree. F.
20. The method of claim 17, wherein the composition further
comprises an additive selected from the group consisting of yerba
mate leaf extract, huperizine, taurine, inositol, niacinamide,
phenylalanine, citicoline, or a salt of any thereof, and a
combination thereof.
21. The method of claim 20, wherein the composition comprises:
about 3.8 wt % caffeine HCl, about 2.5 wt % yerba mate leaf
extract, about 1.times.10.sup.-8 wt % huperizine, about 9.5 wt %
taurine, about 9.5 wt % inositol, about 0.6 wt % niacinamide, about
9.5 wt % phenylalanine, about 7.6 wt % citicoline, about 9.5 wt %
propylene glycol, and about 9.5 wt % glycerol.
22. The method of claim 17, wherein about 0.0002 mg to about 25 mg
of caffeine or a salt thereof is inhaled by the subject per
inhalation.
23. The method of claim 22, wherein about 0.0005 mg to about 10 mg
of caffeine or a salt thereof is inhaled by the subject per
inhalation.
24. The method of claim 22, wherein about 10 mg to about 20 mg of
caffeine or a salt thereof is inhaled by the subject per
inhalation.
25. The method of claim 22, wherein about 20 mg to about 40 mg of
caffeine or a salt thereof is inhaled by the subject per
inhalation.
26. The method of claim 17, wherein the apparatus is a personal
electronic vaporizer.
Description
RELATED APPLICATION
[0001] This application claims the benefit of and priority to U.S.
Provisional Application No. 61/844,772, entitled "INHALABLE
COMPOSITIONS COMPRISING CAFFEINE, METHODS OF USE AND APPARATUS FOR
USING THE SAME" and filed on Jul. 10, 2013, which is incorporated
herein by reference in its entirety for all purposes.
FIELD
[0002] The present technology generally relates to compositions,
methods and an apparatus relating to the pulmonary delivery of an
inhalable composition comprising caffeine.
BACKGROUND
[0003] The following background is provided to assist the
understanding of the reader. None of the information provided or
references cited is admitted to be prior art to the present
invention.
[0004] Caffeine is a bitter substance that acts on many humans as a
central nervous system stimulant, temporarily warding off
drowsiness and restoring alertness. It is the most widely used of
all psychoactive drugs. Caffeine consumption from all sources has
been estimated at around 70 to 76 mg/person/day worldwide and about
210 to 238 mg/day in the US and Canada. In North America, 90% of
adults consume caffeine daily. Daily caffeine consumption may reach
a value of 2.4 to 4.0 mg/kg (170-300 mg) in a 60- to 70-kg
individual, largely from coffee, tea, soft drinks, energy drinks,
and chocolate foods. A cup of coffee, a soft drink or an energy
drink can have about 80-200 mg, 30-60 mg or 60-280 mg caffeine per
serving, respectively.
[0005] Caffeine is a hydrophobic compound with relatively low
solubility in water. The absorption of caffeine by the oral route,
from the gastrointestinal tract, is rapid and reaches 99% in humans
in about 45 minutes after ingestion. However, the oral route has
disadvantages. The consumption of caffeine via soft drinks, energy
drinks and chocolate foods contributes to weight gain and obesity.
The consumption of caffeine from coffee and tea contributes to
stomach aches and gastrointestinal disorders. Withdrawal symptoms
after the discontinuation of caffeine from one's diet may include
headache, irritability, inability to concentrate, drowsiness,
insomnia, and pain in the stomach.
[0006] Therefore, improved formulations of caffeine are needed.
Also needed is an efficient means to administer caffeine more
directly into the blood steam, relative to the oral route and
without the concomitant consumption of foods and beverages that
contain caffeine. For example, it would be desirable to provide
improved methods and compositions for the pulmonary delivery of
caffeine. Although caffeinated powders have been developed for
inhalation, these powders are ineffective because they settle on
the tongue, mouth and throat of a subject where they are
substantially rinsed into the stomach for oral delivery.
[0007] Personal electronic vaporizers such as electronic cigarettes
have been developed for the pulmonary administration of relatively
small concentrations of active compounds. Electronic cigarettes,
which generally include a battery, vaporizer (i.e., atomizer),
chamber to store the liquid and a mouthpiece, have been used to
effectively vaporize actives such as nicotine for pulmonary
administration. The quantity of nicotine delivered by electronic
cigarettes ranges from "low" doses of about 6-8 .mu.g to "ultra
high" doses of about 36-48 .mu.g.
SUMMARY
[0008] Described herein are improved compositions, methods and an
apparatus relating to the pulmonary delivery of an inhalable
composition comprising caffeine, or a salt thereof, and a solvent
selected from the group consisting of propylene glycol, glycerol,
ethanol, and a combination thereof. Inhalable compositions have
been developed that maintain caffeine, or a salt thereof, in
aqueous solution and allow such aqueous solutions of caffeine to be
heated and vaporized by an apparatus, such as a personal electronic
vaporizer or an electronic cigarette, for pulmonary administration
to a subject. Following inhalation of the caffeine by the subject,
systemic absorption occurs through the thin layer of epithelial
cells in the alveolar regions of the lung. Such pulmonary delivery
of caffeine may provide more rapid systemic availability than does
the oral route and avoids stomach irritation and the need to
consume foods or beverages that contain caffeine.
[0009] In one aspect, an inhalable composition is provided,
comprising caffeine, or a salt thereof, and a solvent selected from
the group consisting of propylene glycol, glycerol, ethanol, and a
combination thereof. In one embodiment, the inhalable composition
further comprises water. Applicants have developed inhalable
compositions having suitable ratios of propylene glycol, ethanol
and glycerol that retain the caffeine in solution, such as an
aqueous solution, and allow it to be efficiently vaporized.
Applicants have further developed such inhalable compositions
having additional additives, some of which further improve the
overall solubility of caffeine. For example, in one non-limiting
embodiment, the inhalable composition comprises: about 1 wt. % to
about 10 wt % caffeine HCl, about 1 wt. % to about 10 wt % yerba
mate leaf extract, about 1.times.10.sup.-10 wt. % to about
1.times.10.sup.-5 wt % huperizine, about 1 wt. % to about 30 wt %
taurine, about 1 wt. % to about 30 wt % inositol, about 0.1 wt. %
to about 3 wt % niacinamide, about 1 wt. % to about 30 wt %
phenylalanine, about 1 wt. % to about 30 wt % citicoline, about 1
wt. % to about 30 wt % propylene glycol, about 1 wt. % to about 30
wt % glycerol and water.
[0010] In one aspect, an apparatus is provided for the pulmonary
administration of an inhalable composition to a subject, wherein:
the apparatus is a personal electronic vaporizer; the inhalable
composition comprises caffeine, or a salt thereof, and a
water-miscible solvent selected from the group consisting of
propylene glycol, glycerol, ethanol and a combination thereof; and
the apparatus comprises a means to store the inhalable composition
as a liquid, a means to heat and transform the liquid into a vapor
and a means to administer at least 0.0001 mg caffeine, or a salt
thereof, from the vapor to the subject per inhalation by the
subject from the apparatus. In one embodiment, the apparatus
comprises the inhalable composition.
[0011] In yet another aspect, a method is provided for
administering an inhalable composition to a subject in need
thereof, the method comprising providing the subject with the
inhalable composition comprising caffeine, or a salt thereof, and a
solvent selected from the group consisting of propylene glycol,
glycerol, ethanol and a combination thereof; and an apparatus for
the pulmonary administration of the inhalable composition; wherein
the method results in a pulmonary administration of at least 0.0001
mg of caffeine from the inhalable composition to the subject.
BRIEF DESCRIPTION OF THE FIGURES
[0012] FIG. 1 is a top exterior view of an exemplary apparatus
described herein, according to one illustrative implementation.
[0013] FIG. 2 is an interior view of an exemplary apparatus
described herein, according to one illustrative implementation.
DETAILED DESCRIPTION
[0014] In the following detailed description, reference is made to
the accompanying drawings, which form a part thereof. The
illustrative embodiments described in the detailed description,
drawings and claims are not meant to be limiting. Other embodiments
may be utilized, and other changes may be made, without departing
from the spirit or scope of the subject matter presented here. The
present technology is also illustrated by the examples herein,
which should not be construed as limiting in any way.
[0015] As used herein, the term "pulmonary delivery" means that the
mode of delivery targets the lungs of a subject as a means to enter
the blood stream of the subject. Generally, not all of a given
dosage that is administered by pulmonary delivery reaches both the
lungs and the blood stream of the subject. Rather, just a fraction
of the dosage that is administered by pulmonary delivery reaches
both the lungs and the blood stream of the subject.
[0016] As used herein, the terms "glycerol," "glycerin," "vegetable
glycerin" and "vegetable glycerol" are used interchangeably.
[0017] As used herein, the term "vapor" is used to describe a
droplet of liquid that is substantially free (e.g., at least 80-99%
free) of solids.
[0018] As used herein, the term "water-miscible solvent" is meant
to include all solvents other than water that dissolve with water
at a 1:1 ratio at 25.degree. C.
[0019] As used herein, the terms "personal electronic vaporizer"
and "vaporizer" are meant to include all such devices, including
and resembling electronic cigarettes that are known to those of
ordinary skill in the art in addition to the personal electronic
vaporizer apparatus that is disclosed herein. Non-limiting
representative electronic cigarettes are described in the published
patent applications US 2012/0273589 and US 2012/0279512, both to
Lik Hon.
[0020] As used herein, "active ingredient" refers to a compound
that provides a pharmacological activity. By way of example, but
not by way of limitation, in some embodiments, active ingredients
include, but are not limited to, caffeine, panax ginseng, gingko
biloba, bitter orange, cola-nut, guarana, natrum carbonicum, green
tea, cocoa extract, and yerba mate.
[0021] As used herein, "inactive ingredient" refers to an inert
compound or substance. In some embodiments, an inactive ingredient
serves as a diluent or vehicle for the compound. By way of example,
but not by way of limitation, in some embodiments, inactive
ingredients include, but are not limited to, USP Kosher propylene
glycol, USP Kosher vegetable glycerin, P57 Hoodia, ethanol, water,
natural flavoring, inositol, and N-acetyl L tyrosine.
A. INHALABLE COMPOSITIONS
[0022] Described herein, in one aspect, are inhalable compositions
comprising caffeine, or a salt thereof, and one or more
water-miscible solvents, wherein the one or more water-miscible
solvents each has a boiling point greater than 150.degree. C. In
one embodiment, the water-miscible solvent is selected from the
group consisting of propylene glycol, glycerol, ethanol and a
combination thereof. These inhalable compositions are formulated
for pulmonary delivery to a subject. Specifically, the inhalable
compositions are formulated for vaporization by an apparatus, such
as a personal electronic vaporizer or electronic cigarette that
stores the inhalable composition as a liquid, heats the inhalable
composition into a vapor phase and delivers the inhalable
composition to the subject as a vapor via inhalation.
[0023] It is contemplated that, because lung tissue is sensitive to
absorption, the stimulating effects of caffeine will be felt by a
subject sooner (e.g., 1-10 minutes) upon inhalation relative to the
longer periods (e.g., 30-45 minutes) required for caffeine to take
effect upon ingestion. Upon pulmonary administration, caffeine
bypasses acid and bile in the stomach, and is expected to reach the
central nervous system sooner than the oral route. It is
contemplated that the inhalable compositions described herein will
not cause stomach aches that can occur following the consumption of
coffee or tea.
[0024] As noted, the inhalable compositions described herein
include caffeine, or a salt thereof, and a water-miscible solvent,
particularly those selected from the group consisting of propylene
glycol, glycerol, ethanol and a combination thereof. Propylene
glycol, having a boiling point of 188.2.degree. C. and glycerol
having a boiling point of 290.degree. C., act as solvents and as
thickening agents. Propylene glycol, glycerol and ethanol also
provide a relatively even heating of the inhalable composition as
it is vaporized by the apparatus. Further, propylene glycol,
glycerol and ethanol provide tangible plumes of vapor that retain
the caffeine within the vapor droplets.
[0025] The quantity of propylene glycol that is added to the
inhalable compositions described herein can and will vary. In some
embodiments the inhalable compositions described herein comprise 0
wt. %, 1 wt. %, 2 wt. %, 3 wt. %, 4 wt. %, 5 wt. %, 6 wt. %, 7 wt.
%, 8 wt. %, 9 wt. %, 9.5 wt. %, 10 wt. %, 10.5 wt. %, 11 wt. %, 12
wt. %, 13 wt. %, 14 wt. %, 15 wt. %, 16 wt. %, 17 wt. %, 18 wt. %,
19 wt. %, 20 wt. %, 30 wt. %, 40 wt. %, 50 wt. % or a percentage
between any two of these values of propylene glycol relative to the
of the entire inhalable composition comprising caffeine. In some
embodiments, the inhalable composition comprises propylene glycol
and does not contain glycerol.
[0026] The quantity of glycerol that is added to the inhalable
compositions described herein can and will vary. In some
embodiments the inhalable compositions described herein comprise 0
wt. %, 1 wt. %, 2 wt. %, 3 wt. %, 4 wt. %, 5 wt. %, 6 wt. %, 7 wt.
%, 8 wt. %, 9 wt. %, 9.5 wt. %, 10 wt. %, 10.5 wt. %, 11 wt. %, 12
wt. %, 13 wt. %, 14 wt. %, 15 wt. %, 16 wt. %, 17 wt. %, 18 wt. %,
19 wt. %, 20 wt. %, 30 wt. %, 40 wt. %, 50 wt. % or a percentage
between any two of these values of glycerol relative to the of the
entire inhalable composition comprising caffeine. In some
embodiments, the inhalable composition comprises glycerol and does
not contain propylene glycol.
[0027] The quantity of ethanol that is added to the inhalable
compositions described herein can and will vary. In some
embodiments the inhalable compositions described herein comprise 0
wt. %, 1 wt. %, 2 wt. %, 3 wt. %, 4 wt. %, 5 wt. %, 6 wt. %, 7 wt.
%, 8 wt. %, 9 wt. %, 9.5 wt. %, 10 wt. %, 10.5 wt. %, 11 wt. %, 12
wt. %, 13 wt. %, 14 wt. %, 15 wt. %, 16 wt. %, 17 wt. %, 18 wt. %,
19 wt. %, 20 wt. %, 30 wt. %, 40 wt. %, 50 wt. % or a percentage
between any two of these values of ethanol relative to the of the
entire inhalable composition comprising caffeine. In some
embodiments, the inhalable composition comprises ethanol and does
not contain glycerol or propylene glycol.
[0028] In some embodiments, the inhalable composition described
herein comprises propylene glycol and glycerol, each in any of the
wt % amounts described herein, such that the inhalable composition
has a wt/wt % ratio of propylene glycol to glycerol (i.e.,
propylene glycol:glycerol) of 1:1,000, 1:500, 1:100, 1:50, 1:25,
1:20, 1:15, 1:10, 1:5, 1:4, 1:3, 1:2, 1.1.5, 1:1.4, 1:1.3, 1:1.2,
1:1.1, 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 2:1, 3:1, 4:1, 5:1,
10:1, 15:1, 20:1, 25:1, 50:1, 100:1, 1,000:1 or a ration between
any two of these values. In some embodiments, the inhalable
composition comprises propylene glycol and glycerol, and the
inhalable composition has a ratio of propylene glycol to glycerol
of about 2:1 to about 1:2.
[0029] In some embodiments, the inhalable composition described
herein comprises propylene glycol and ethanol, each in any of the
wt % amounts described herein, such that the inhalable composition
has a wt/wt % ratio of propylene glycol to ethanol (i.e., propylene
glycol:ethanol) of 1:1,000, 1:500, 1:100, 1:50, 1:25, 1:20, 1:15,
1:10, 1:5, 1:4, 1:3, 1:2, 1.1.5, 1:1.4, 1:1.3, 1:1.2, 1:1.1, 1:1,
1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 2:1, 3:1, 4:1, 5:1, 10:1, 15:1,
20:1, 25:1, 50:1, 100:1, 1,000:1 or a ration between any two of
these values. In some embodiments, the inhalable composition
comprises propylene glycol and ethanol, and the inhalable
composition has a ratio of propylene glycol to ethanol of about 2:1
to about 1:2.
[0030] In some embodiments, the inhalable composition described
herein comprises ethanol and glycerol, each in any of the wt %
amounts described herein, such that the inhalable composition has a
wt/wt % ratio of ethanol to glycerol (i.e., ethanol:glycerol) of
1:1,000, 1:500, 1:100, 1:50, 1:25, 1:20, 1:15, 1:10, 1:5, 1:4, 1:3,
1:2, 1.1.5, 1:1.4, 1:1.3, 1:1.2, 1:1.1, 1:1, 1.1:1, 1.2:1, 1.3:1,
1.4:1, 1.5:1, 2:1, 3:1, 4:1, 5:1, 10:1, 15:1, 20:1, 25:1, 50:1,
100:1, 1,000:1 or a ration between any two of these values. In some
embodiments, the inhalable composition comprises ethanol and
glycerol, and the inhalable composition has a ratio of ethanol to
glycerol of about 2:1 to about 1:2.
[0031] In some embodiments, the inhalable composition described
herein comprises propylene glycol, ethanol, and glycerol, each in
any of the wt % amounts described herein.
[0032] In any of the embodiments described herein, the inhalable
composition further comprises water. In some embodiments the
inhalable composition described herein comprises 0 wt. %, 1 wt. %,
2 wt. %, 3 wt. %, 4 wt. %, 5 wt. %, 6 wt. %, 7 wt. %, 8 wt. %, 9
wt. %, 9.5 wt. %, 10 wt. %, 10.5 wt. %, 11 wt. %, 12 wt. %, 13 wt.
%, 14 wt. %, 15 wt. %, 16 wt. %, 17 wt. %, 18 wt. %, 19 wt. %, 20
wt. %, 30 wt. %, 40 wt. %, 50 wt. %, 60 wt. %, 70 wt. %, 80 wt. %,
90 wt. %, or a percentage between any two of these values of water
relative to the of the entire inhalable composition comprising
caffeine.
[0033] In some embodiments, the inhalable composition described
herein is a vapor comprising liquid droplets. The liquid droplets
have an average diameter that facilitates administration of the
caffeine within the droplets to the subject via the pulmonary
route. For example, the liquid droplets may have an average
diameter of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
15, 16, 17, 18, 19, 20 microns, or an average diameter between any
two of these values.
[0034] In some embodiments, the inhalable compositions described
herein further comprise suitable additives. For example, in some
embodiments, the inhalable composition further comprises one or
more additives such as yerba mate leaf extract, huperizine,
taurine, inositol, niacinamide, phenylalanine, citicoline, or a
salt of any thereof.
[0035] Yerba Mate extract is the product of yerba mate plant brewed
or distilled so that caffeine (or maffeine) is left in the residue.
The absorption rate of maffeine through the body is slower than
that of caffeine and may produce a more uplifting feeling than
caffeine. Huperzine A may cause an increase in the levels of
acetylcholine in a subject. Huperzine A may also offset the
negative jitteriness that caffeine may cause in a subject. Taurine
has been found to help dissolve the caffeine in the inhalable
compositions described herein and may also help to facilitate the
absorption of caffeine into the blood. Taurine may also minimize
the caffeine crash that occurs in some patients following
administration of caffeine. Taurine may also serve as a relaxant to
offset the jitteriness caused by caffeine and help a subject go to
sleep. Inositol is a flavorant that improves the taste of inhalable
compositions comprising caffeine. Specifically, it reduces the
bitterness of caffeine. Inositol has also been found improve the
solubility of caffeine in the inhalable compositions described
herein. Niacinamide, also known as vitamin B-3, plays important
roles in the energy production process in cells. Niacinamide boosts
the effects of caffeine to create longer lasting stimulation in a
subject. Niacinamide may also help reduce the "short of breath"
feeling that some people complain of after ingesting caffeine.
Phenylalanine may reduce caffeine headache associated with caffeine
and may also help with caffeine withdrawal. Citicoline may play a
role in neurotransmission and might help support brain
function.
[0036] Other suitable additives include, but are not limited to,
N-Acetyl L Tyrosine, Panax Ginseng (Aralia quinquefolia), Gingko
Biloba (Ginkgo biloba L.), Bitter Orange (Citrus aurantium L.),
Cola-Nut (Cola acuminate), Guarana (Paullinia cupana), Natrum
Carbonicum, Green Tea (Camellia sinensis), Cocoa Extract (Theobroma
cacao L.), Licorice (Glycyrrhiza glabra L.), Natrum Carbonicum,
Ginger (Zingiber officinale Rosc.), P57 Hoodia, Glucuronolactone,
Yerba Mate (Ilex paraguensis St. Hil.), Garcinia Cambogia, Hoodia
Gordonii, Kelp, and Peppermint (Mentholum). In some embodiments,
the additional additives are useful for energy and/or diet support.
In some embodiments, the additional additives are natural
flavoring.
[0037] In one non-limiting embodiment, the inhalable composition
comprises about 1 wt. % to about 10 wt % caffeine HCl, about 1 wt.
% to about 10 wt % yerba mate leaf extract, about
1.times.10.sup.-10 wt. % to about 1.times.10.sup.-5 wt %
huperizine, about 1 wt. % to about 30 wt % taurine, about 1 wt. %
to about 30 wt % inositol, about 0.1 wt. % to about 3 wt %
niacinamide, about 1 wt. % to about 30 wt % phenylalanine, about 1
wt. % to about 30 wt % citicoline, about 1 wt. % to about 30 wt %
propylene glycol, about 1 wt. % to about 30 wt % glycerol, and
water.
[0038] In another embodiment, the inhalable composition comprises
about 1-5 wt % caffeine HCl, about 1-5 wt % yerba mate leaf
extract, about 1.times.10.sup.-9 to 1.times.10.sup.-6 wt %
huperizine, about 1-15 wt % taurine, about 1-15 wt % inositol,
about 0.1-2.0 wt % niacinamide, about 1-15 wt % phenylalanine,
about 1-15 wt % citicoline, about 1-15 wt % propylene glycol, about
1-15 wt % glycerol, and water. In some embodiments, the water is
de-ionized water.
[0039] In another embodiment, the inhalable composition comprises
about 3.8 wt % caffeine HCl, about 2.5 wt % yerba mate leaf
extract, about 1.times.10.sup.-8 wt % huperizine, about 9.5 wt %
taurine, about 9.5 wt % inositol, about 0.6 wt % niacinamide, about
9.5 wt % phenylalanine, about 7.6 wt % citicoline, about 9.5 wt %
propylene glycol, about 9.5 wt % glycerol, and water. In some
embodiments, the water is de-ionized water.
[0040] In one embodiment, the inhalable composition further
comprises about 1 wt %, 5 wt %, 10 wt %, 15 wt %, 20 wt %, 25 wt %,
30 wt %, or a range between any two of these values, of a
flavorant. For example, the flavorant may be selected from the
group consisting of citric acid, lemon extract, lime extract,
orange extract, peppermint, spearmint, cinnamon and a combination
thereof.
[0041] In any of the embodiments described herein, the inhalable
composition further comprises nicotine. In some embodiments the
inhalable composition described herein comprises 0 wt. %, 0.1 wt.
%, 0.2 wt. %, 0.3 wt. %, 0.4 wt. %, 0.5 wt. %, 1 wt. %, 2 wt. %, 5
wt. %, or a percentage between any two of these values of nicotine
relative to the of the entire inhalable composition comprising
caffeine.
[0042] In certain embodiments, the inhalable compositions and
formulations described herein are for the pulmonary administered to
a subject (e.g., a human) and may contain one or more
pharmaceutically-acceptable excipients, or carriers. Suitable
excipients and their formulations are described in Remington's
Pharmaceutical Sciences, 16th ed., 1980, Mack Publishing Co.,
edited by Oslo et al. Typically, an appropriate amount of a
pharmaceutically-acceptable salt is used in the formulation to
render the formulation isotonic. Examples of the
pharmaceutically-acceptable excipients include liquids such as
saline, Ringer's solution and dextrose solution.
[0043] The pH of the formulation can be set at any desired level
which is not damaging to lung surfaces. Although it is desirable to
have a low pH formulation (acidic) to avoid interaction with
certain types of plastic containers it is generally more desirable
to have a high pH formulation (basic) to increase the absorption of
the caffeine from the lung into the circulatory system. The pH of
the inhalable compositions described herein is generally from about
3 to about 8, or from about 3 to about 7, although the pH may be
varied. The inhalable composition or formulation may also comprise
a lyophilized powder or other optional excipients suitable to the
present inhalable composition or formulation including sustained
release preparations known to those of skill in the art.
[0044] Other suitable excipients can be added to the inhalable
compositions described herein. For example, the inhalable
compositions or formulations described herein for inhalation can
include, e.g., one or more surfactants to aid in solubility and
stability of formulation constituents. Surfactants can be present
in formulations of the invention in a concentration ranging from
about 0.001 weight percent to about 2 weight percent, or about 0.01
weight percent to about 1 weight percent. The surfactants can
include, e.g., nonionic detergents, such as polyethylene glycol
sorbitan monolaurate (Tween 20), polyoxyethylenesorbitan monooleate
(Tween 80), block copolymers of polyethylene and polypropylene
glycol (Pluronic), non-ionic surfactants, ionic surfactants and/or
the like.
[0045] Examples of suitable non-ionic surfactants are alkylphenyl
alkoxylates, alcohol alkoxylates, fatty amine alkoxylates,
polyoxyethylene glycerol fatty acid esters, castor oil alkoxylates,
fatty acid alkoxylates, fatty acid amide alkoxylates, fatty acid
polydiethanolamides, lanolin ethoxylates, fatty acid polyglycol
esters, isotridecyl alcohol, fatty acid amides, methylcellulose,
fatty acid esters, silicone oils, alkyl polyglycosides, glycerol
fatty acid esters, polyethylene glycol, polypropylene glycol,
polyethylene glycol/polypropylene glycol block copolymers,
polyethylene glycol alkyl ethers, polypropylene glycol alkyl
ethers, polyethylene glycol/polypropylene glycol ether block
copolymers and mixtures of these, polyacrylates and acrylic acid
graft copolymers. Other nonionic surfactants are known per se to
those skilled in the art and have been described in the literature.
Preferred substances are polyethylene glycol, polypropylene glycol,
polyethylene glycol/polypropylene glycol block copolymers,
polyethylene glycol alkyl ethers, polypropylene glycol alkyl
ethers, polyethylene glycol/polypropylene glycol ether block
copolymers and mixtures of these. Particularly preferred
surfactants include polymers of a mixture of polyoxyethylene and
polyoxypropylene such as Pluronic F68 (available from BASF).
[0046] Examples of suitable ionic surfactants are
alkylarylsulfonates, phenylsulfonates, alkyl sulfates, alkyl
sulfonates, alkyl ether sulfates, alkyl aryl ether sulfates, alkyl
polyglycol ether phosphates, polyaryl phenyl ether phosphates,
alkylsulfosuccinates, olefin sulfonates, paraffin sulfonates,
petroleumsulfonates, taurides, sarcosides, fatty acids,
alkylnaphthalenesulfonic acids, naphthalenesulfonic acids,
lignosulfonic acids, condensates of sulfonated naphthalenes with
formaldehyde or with formaldehyde and phenol and, if appropriate,
urea, lignin-sulfite waste liquor, including their alkali metal,
alkaline earth metal, ammonium and amine salts, alkyl phosphates,
quaternary ammonium compounds, amine oxides, betaines, and mixtures
of these. Preferred substances include Pluronic F68 or Pluronic
F188 with polyoxyethylene sorbitan monolaurate (e.g., Tween 20,
available from Sigma) being particularly preferred.
[0047] The inhalable compositions and formulations described herein
may include one or more buffers. Buffers can be present, e.g., to
control pH, enhance stability, affect constituent solubility,
provide comfort on administration, and the like. Formulation pH can
be controlled in the range from about pH 3 to about pH 10, from
about pH 6 to about pH 8, from about pH 7 to about pH 7.4, or about
pH 7.2. Preferred buffers are often paired acid and salt forms of a
buffer anion generally recognized as safe for the particular route
of administration of the bioactive material. Typical buffers for
use in the formulations and inhalable compositions of the invention
include, e.g., potassium phosphate, sodium phosphate, sodium
acetate, histidine, imidazole, sodium citrate, sodium succinate,
ammonium bicarbonate, carbonates, and the like. Generally, buffers
are used at molarities from about 1 mM to about 2 M, with from
about 2 mM to about 1 M being preferred, and from about 10 mM to
about 0.5 M being especially preferred, and 25 mM to 50 mM being
particularly preferred.
[0048] Because the inhalable compositions described herein
comprises propylene glycol, glycerol, ethanol, or a combination
thereof they are generally more viscous than water. In one
embodiment, any of the inhalable compositions described herein has
a viscosity at 20.degree. C. of about 0.001 Pas, about 0.01 Pas,
about 0.1 Pas, about 1.0 Pas, about 1.5 Pas, or a viscosity between
any two of the these values.
[0049] The inhalable compositions described herein are formulated
to provide at least 0.0001 mg of caffeine to a subject per
inhalation of any one of these compositions. For example, the
inhalable compositions described herein may be formulated to
provide at least about 0.0001, 0.001, 0.01, 0.1, 1, 2, 3, 4, 5, 6,
7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35,
40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 100, 105, 110, 125,
120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180,
185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245,
250, 255, 260, 265, 270, 275, 280, 285, 290, 295, 300 mg, or an
amount between any two of these values, of caffeine or a salt
thereof, to the subject per inhalation (i.e., vape). Thus, in some
embodiments, the composition is formulated to provide about 0.0001
mg to about 10 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 10 mg to about 20 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 20 mg
to about 30 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 30 mg to about 40 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 40 mg
to about 50 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 50 mg to about 60 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 60 mg
to about 70 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 70 mg to about 80 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 80 mg
to about 90 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 90 mg to about 100 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 100 mg
to about 110 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 110 mg to about 120 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 120 mg
to about 130 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 130 mg to about 140 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 140 mg
to about 150 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 150 mg to about 160 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 160 mg
to about 170 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 170 mg to about 180 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 180 mg
to about 190 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 190 mg to about 200 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 200 mg
to about 210 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 210 mg to about 220 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 220 mg
to about 230 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 230 mg to about 240 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 240 mg
to about 250 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 250 mg to about 260 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 260 mg
to about 270 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 270 mg to about 280 mg of caffeine or a
salt thereof to the subject per inhalation by the subject. In some
embodiments, the composition is formulated to provide about 280 mg
to about 290 mg of caffeine or a salt thereof to the subject per
inhalation by the subject. In some embodiments, the composition is
formulated to provide about 290 mg to about 300 mg of caffeine or a
salt thereof to the subject per inhalation by the subject.
[0050] The inhalable compositions described herein are formulated
to provide less than 1 mg of nicotine to a subject per inhalation
of any one of these compositions. For example, the inhalable
compositions described herein may be formulated to provide at least
about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,
18, 19, 20, 25, 30, 35, 40, 45 or 50 .mu.g, or an amount between
any two of these values, of nicotine or a salt thereof, to the
subject per inhalation (i.e., vape).
[0051] In another embodiment, the inhalable compositions of the
present technology includes one or more active ingredients selected
from the group consisting of Caffeine (Caffeinum), Panax Ginseng
(Aralia quinquefolia), Gingko Biloba (Ginkgo biloba L.), Bitter
Orange (Citrus aurantium L.), Cola-Nut (Cola acuminate), Guarana
(Paullinia cupana), Natrum Carbonicum, Green Tea (Camellia
sinensis), Cocoa Extract (Theobroma cacao L.), and Yerba Mate (Ilex
paraguensis St. Hil.). In some embodiments, the inhalable
composition also includes one or more inactive ingredients selected
from the group consisting of USP Kosher propylene glycol, USP
Kosher vegetable glycerin, ethanol, water, glucuronolactone,
natural flavoring, inositol, and N-acetyl L tyrosine. In some
embodiments, the inhalable composition provides energy.
[0052] In another embodiment, the inhalable compositions of the
present technology includes one or more active ingredients selected
from the group consisting of Caffeine (Caffeinum), Peppermint
(Mentholum), Bitter Orange (Citrus aurantium L.), Green Tea
(Camellia sinensis), Licorice (Glycyrrhiza glabra L.), Natrum
Carbonicum, Ginger (Zingiber officinale Rosc.), Garcinia Cambogia,
Hoodia Gordonii, Kelp, and Yerba Mate (Ilex paraguensis St. Hil.).
In some embodiments, the inhalable composition also includes one or
more inactive ingredients selected from the group consisting of USP
Kosher propylene glycol, USP Kosher vegetable glycerin, P57 Hoodia,
ethanol, water, natural flavoring, inositol, and N-acetyl L
tyrosine. In some embodiments, the inhalable composition provides
energy. In some embodiments, the inhalable composition provides
diet support.
B. APPARATUS
[0053] FIG. 1 is a top view of an exemplary implementation of a
vaporizer apparatus 100 (also referred to as a vaporizer 100). The
exterior of the vaporizer 100 may include the body section 102 and
the mouthpiece 104. As described below, the body 104 of the
vaporizer 100 may store the components that are responsible for the
function and control of the vaporizer 100. The mouthpiece 104 may
house the cartridge used to store the inhalable composition. In
general, when a user inhales on the mouthpiece 104, the vaporizer
100 delivers a predetermined amount of the inhalable composition to
the user in a vapor form.
[0054] FIG. 2 is a side view of the vaporizer 100. FIG. 2
illustrates an exemplary configuration of the layout of components
within the vaporizer 100. As a brief overview, the vaporizer 100
may include a cartridge 106, an atomizer 108, a controller 110, and
a power supply 112.
[0055] Now referring to the components of the vaporizer 100 in
greater detail. The cartridge 106 may be configured to house any of
the inhalable composition described herein. In some
implementations, the inhalable composition includes an additive
selected from the group consisting of yerba mate leaf extract,
huperizine, taurine, inositol, niacinamide, phenylalanine,
citicoline, or a salt of any thereof, and a combination
thereof.
[0056] The housing of the cartridge 106 may be made from any food
grade material. For example, the housing of the cartridge 106 may
include polyethylene terephthalate, high density polyethylene,
polyvinyl chloride, or any combination thereof. In other
implementations, the housing of the cartridge 106 may include
metals or allows. In some implementations, the cartridge 106 is
configured to allow the inhalable composition to pass to the
atomizer 108 in a liquid form and then pass through the mouthpiece
104 to the user in a vapor form. The cartridge 106 may include an
air-liquid separator which allows the inhalable composition to exit
the mouthpiece 104 in substantially only vapor form and not liquid
form. In some implementations, the air-liquid separator is a sponge
or membrane.
[0057] In some implementations, the cartridge 106 is refillable and
in some implementations the cartridge 106 is disposed of once the
inhalable composition is consumed. The cartridge 106 may be a
component of, or coupled to the mouthpiece 104, such that the
mouthpiece 104 section may be replaced when replacing the cartridge
106. In some implementations, the mouthpiece 104 and/or the body
102 (and components housed within the body 102) of the vaporizer
100 may be reusable. For example, once the inhalable composition
within the cartridge 106 has been consumed, a user may replace the
cartridge 106 and continue using the vaporizer 100. In other
implementations, the vaporizer 100 may be disposed of after the
inhalable composition in the cartridge 106 is consumed.
[0058] In some implementations, the cartridge 106 may be configured
to store an inhalable composition that includes between about
0.0001 mg and about 10 mg, between about 0.001 mg and about 5 mg,
between about 0.01 mg and about 2.5 mg, or between about 0.1 mg and
1.0 mg of caffeine in solution. In some implementation, the
cartridge 106 may be configured to store an inhalable composition
that includes between about 10 mg and about 200 mg, between about
30 mg and about 180 mg, between about 50 mg and about 160 mg,
between about 70 mg and about 140 mg, between about 90 mg and about
120 mg, or between about 100 mg and about 110 mg of caffeine in
solution. In some embodiments, the cartridge 106 may be configured
to store an inhalable composition that includes between about 200
mg and about 2000 mg, between about 400 mg and about 1800 mg,
between about 600 mg and about 1600 mg, between about 800 mg and
about 1400 mg, or between about 1000 mg and about 1200 mg of
caffeine in solution.
[0059] The cartridge 106 may be coupled to the atomizer 108 such
that between about 0.0001 mg and about 5 mg, between about 5 mg and
15 mg, between about 15 mg and 25 mg, between about 25 mg and 30
mg, between about 30 mg and 35 mg, between about 35 mg and 40 mg,
between about 40 mg and 45 mg, between about 45 mg and 50 mg,
between about 50 mg and 55 mg, between about 55 mg and 60 mg,
between about 60 mg and 65 mg, between about 65 mg and 70 mg,
between about 70 mg and 85 mg, between about 85 mg and 90 mg,
between about 90 mg and 95 mg, between about 95 mg and 100 mg,
between about 100 mg and 105 mg, between about 105 mg and 110 mg,
between about 110 mg and 120 mg, between about 120 mg and 130 mg,
between about 130 mg and 140 mg, between about 140 mg and 150 mg,
between about 150 mg and 160 mg, between about 160 mg and 170 mg,
between about 170 mg and 180 mg, between about 180 mg and 190 mg,
between about 190 mg and 200 mg, between about 200 mg and 210 mg,
between about 210 mg and 220 mg, between about 220 mg and 230 mg,
between about 230 mg and 240 mg, between about 240 mg and 250 mg,
between about 250 mg and 260 mg, between about 260 mg and 270 mg,
between about 270 mg and 280 mg, between 280 mg and 290 mg, or
between 290 mg and 300 mg of caffeine is delivered to the atomizer
108 during each inhalation cycle of the device. In some
implementations, the coupling between the cartridge 106 and the
atomizer 108 may include a fluid flow channel. In some
implementations, the inhalable composition may be drawn into the
atomizer 108 through capillary action. For example, a wicking
metal, such as silica, may draw the liquid inhalable composition
from the cartridge 106 to the atomizer 108.
[0060] Once the inhalable composition is received by the atomizer
108, the atomizer 108 vaporizes the inhalable composition. In some
implementations, the atomizer 108 may include a heating element
that heats and vaporizes the inhalable composition. The atomizer
108 may heat the inhalable compositions comprising caffeine, or a
salt thereof, and a solvent selected from the group consisting of
propylene glycol, glycerol, ethanol and a combination thereof, to
form a vapor. In some embodiments, the atomizer 108 heats the
inhalable composition into a vapor at about 250.degree. F.,
300.degree. F., 350.degree. F., 400.degree. F., 450.degree. F.,
500.degree. F., 550.degree. F., or a temperature between any two of
these values. In one embodiment, the vaporizer 100 is an electronic
cigarette. The vaporized inhalable composition may be referred to
as a vapor and may include liquid droplets of caffeine, which may
be inhaled by the user.
[0061] The size distribution of the diameter of the vapor droplets
that are delivered by the apparatus is important to the therapeutic
efficacy of the caffeine within the inhalable composition when
delivered by inhalation. Liquid droplets of greater than about 20
micrometers in mean aerodynamic diameter generally achieve reduced
entry into the lungs and are captured in the nasal-pharyngeal
passages. Thus, the caffeine compositions for inhalation, as
described herein, to be delivered via pulmonary administration, are
generally formulated so that the median aerodynamic diameter of the
vapor droplets is below about 10 micrometers. The size distribution
of the diameter of the vapor droplets is within a size range of
about between about 0.5, 1, 2.5, 10, 20 microns in diameter. The
smaller droplet sizes, on the order of 0.5 to 2.5 micrometers, are
prepared for delivery of caffeine to the alveolar sacs deep in the
lungs. Droplet size may be selected to stimulate either the upper
respiratory tract or the lower respiratory tract or both. Further,
the vapor and each inhalation thereof may contain caffeine in an
amount of about 0.0001 mg to about 20.0 mg per inhalation.
[0062] In one implementation, the vaporizer 100 includes a porous
membrane. As indicated above the rate and amount of caffeine that
can be absorbed can be varied by changing the constituent (e.g.,
caffeine, propylene glycol, glycerol and/or ethanol) concentration
of and/or pH of the caffeine inhalable composition in the packets.
However, it is also possible to decrease the amount of caffeine
actually delivered to the patient's circulatory system by changing
the size of the pores in the membrane. When the pore size is in a
preferred range then a relatively high amount of the formulation,
when aerosolized, will reach the subject's deep lungs and rapidly
move from the lungs into the subject's circulatory system. However,
by making the pores larger the aerosolized droplets created also
become larger. The larger droplets will not move into the deep
lungs as efficiently as the smaller droplets. For example, with
oral inhalation at high to moderate inspiratory flow rates, a
significant number of droplets with aerodynamic size greater than 5
micron would deposit in the oropharynx from where they are not
rapidly absorbed into the subject's circulatory system.
[0063] Although the vaporizer 100 described herein can be
configured to target certain areas of the respiratory tract with
the inhalable compositions described herein, it will be understood
by those skilled in the art that it will not be possible to provide
an apparatus which exclusively administers droplets only to a
particular area of a respiratory tract. In general, smaller size
droplets will deposit in the lung more deeply as compared to larger
size droplets. Further, it is generally not desirable to make the
droplets smaller than 0.5 microns. When the droplets are
sufficiently small, they can be inhaled and exhaled back out
without being deposited at all, unless the subject holds their
breath for sufficient length of time, typically several seconds,
for those droplets to deposit. Further, it is generally not
desirable to make the droplets larger than 20 microns because
droplets which are larger than this size generally deposit very
high up in the respiratory tract and as such do not reach the blood
quickly. When referring to targeting an area of the respiratory
tract those skilled in the art will understand that it is matter of
probabilities of deposition and that those probabilities can vary
based on the size of the droplets. It is also understood by those
skilled in the art that vaporized droplets often do not have a
stable size. For example, droplets can pick up moisture from the
air in the respiratory tract and grow in size. Volatile components
of droplets can evaporate and make the droplet size smaller. These
changes may also cause changes in the density of the droplets that
affects their aerodynamic size.
[0064] Referring again to the vaporizer 100, the atomizer 108 may
be coupled to the controller 110 and/or the power supply 112. In
some implementations, the controller 110 may include a
microprocessor. The controller 110 may also include computer
readable media on which processor executable instructions are
stored. When executed by the microprocessor, the instructions may
cause the microprocessor heat the atomizer 108 to one of the above
described predetermined temperatures in order to vaporize the
inhalable composition. Additionally, and as described further
below, the controller 110 may also regulate the amount of caffeine
that a user may ingest.
[0065] The controller 110 may control the activation of the
atomizer 108, and thus the dosage of caffeine that is delivered to
a user. For example, the controller 110 may include a flow sensor,
which may detect the inhalation of a user and activate the atomizer
108. In other implementations, the controller 110 may activate the
atomizer 108 when the user activates a button or other switch
located on the vaporizer 100. In some implementations, the
controller 110 allows the user to select what temperature the
atomizer 108 heats the liquid inhalable composition.
[0066] When executed the processor executable instructions may
cause the controller 110 to limit or control the amount of caffeine
and/or inhalable composition a user may ingest. In one embodiment,
the controller 112 provides a delay of about 4 to 10 seconds
between inhalations (i.e., vapes). The delay may promote the safety
of the user. In some implementations, the user may require from
about 1 to about 40 vapes to administer an effective dose of
caffeine equivalent to that found in a cup of coffee (e.g., about
200 mg of caffeine).
[0067] As noted, the controller may allow the vaporizer 100 to
administer at least 0.0001 mg caffeine, or a salt thereof, such as
about 2 mg to about 50 mg, from the vaporizer 100 to the user per
inhalation by the user. As such, the vaporizer 100 described herein
can be used to administer one or more inhalations to a user to
achieve an effective dose of approximately 20, 40, 60, 80, 100, 200
mg or more of caffeine to a subject over the course of one or more
inhalations from the vaporizer 100 by the user.
[0068] In some implementations, the controller 110 may cause the
vaporizer 100 to enter a refractory state for a predetermined
amount of time after the administration of one or more vapes.
During the refractory period, the controller 110 may not allow the
vaporizer 100 to administer additional vapes to the user. For
example, after a user draws two inhalations, the controller 110 may
not allow another inhalation to be drawn from the vaporizer 100 for
4 hours. The predetermined amount of time may be between about 15
minutes and about 30 minutes, between about 30 minutes and about 1
hour, between about 1 hour and about 4 hours, between about 4 hours
and about 8 hours, and between about 8 hours and about 24
hours.
[0069] In a similar implementation, the controller 110 may limit
the number of vapes (or caffeine) that may be administered within a
predetermined time window. In these implementations, the vaporizer
100 may not enter a refractory state until a predetermined number
of vapes have been administered. For example, the controller 110
may allow the user to draw 10 vapes over the course of one hour. In
some implementations, the predetermined amount of time may be
between about 15 minutes and about 30 minutes, between about 30
minutes and about 1 hour, between about 1 hour and about 4 hours,
between about 4 hours and about 8 hours, and between about 8 hours
and about 24 hours.
[0070] In general, the above described control sequences, or
similar control sequences, may be used to limit the amount of
caffeine that a user is allowed to consume via the vaporizer 100.
The controller 110 may control the inter-vape timing, the amount of
caffeine per vape, and the amount of caffeine in a dosage cycle
(i.e., the amount of caffeine that a user is allowed to ingest over
a given predetermined time window). The controller 110 may limit
the amount of caffeine in a dosage cycle to between about 0.0001 mg
and about 5 mg, between about 5 mg and about 15 mg, between about
15 mg and about 50 mg, between about 50 mg and about 100 mg,
between about 100 mg and about 500 mg of caffeine, and, as
described above, the predetermined amount of time may range from 15
minutes to 24 hours.
[0071] In some implementations, controller 110 may include analog
circuitry and the control methods described herein may implemented
with analog logic and/or digital logic.
[0072] The vaporizer 100 is powered by a power supply 112. In some
implementations, the power supply 112 is a battery. The battery may
be a rechargeable battery, such as a lithium ion battery. In some
implementations, the battery may be recharged without removing the
battery from the vaporizer 100. In other implementations, the power
supply 112 may be a non-rechargeable battery. In yet other
implementations, the power supply 112 may include an AC
(alternating current) adapter that allows the vaporizer 100 to be
powered by alternating current (e.g., power from a wall outlet).
The power supply 112 may provide between about 3 V and 9 V of
electricity of the vaporizer 100.
C. METHODS OF USE
[0073] In yet another aspect, a method is provided for
administering an inhalable composition to a subject in need
thereof, the method comprising providing the subject with: (a) the
inhalable composition comprising caffeine, or a salt thereof, and a
solvent selected from the group consisting of propylene glycol,
glycerol, ethanol and a combination thereof; and (b) an apparatus
for the pulmonary administration of the inhalable composition;
wherein the method results in a pulmonary administration of at
least 0.0001 mg of caffeine from the inhalable composition to the
subject. In one embodiment, the method further comprises
instructing the subject to inhale the inhalable composition from
the apparatus.
[0074] In one embodiment of the method, the inhalable composition
is any of the inhalable compositions described herein. For example,
the inhalable composition may further comprise yerba mate leaf
extract, huperizine, taurine, inositol, niacinamide, phenylalanine,
citicoline, or a salt of any thereof, propylene glycol, glycerol,
ethanol and water.
[0075] In one embodiment of the method, the inhalable composition
comprises: about 3.8 wt % caffeine HCl, about 2.5 wt % yerba mate
leaf extract, about 1.times.10.sup.-8 wt % huperizine, about 9.5 wt
% taurine, about 9.5 wt % inositol, about 0.6 wt % niacinamide,
about 9.5 wt % phenylalanine, about 7.6 wt % citicoline, about 9.5
wt % propylene glycol, about 9.5 wt % glycerol, and water.
[0076] In some embodiments of the method, about 1, 2, 3, 4, 5, 6,
7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35,
40, 45 or 50 mg, or an amount between any two of these values, of
caffeine or a salt thereof is inhaled by the subject per inhalation
(i.e., vape). Thus, in some embodiments of the method, about 0.0005
mg to about 10 mg of caffeine or a salt thereof is inhaled by the
subject per inhalation. In some embodiments of the method, about 10
mg to about 20 mg of caffeine or a salt thereof is inhaled by the
subject per inhalation. In some embodiments of the method, about 20
mg to about 30 mg of caffeine or a salt thereof is inhaled by the
subject per inhalation. In some embodiments of the method, about 30
mg to about 40 mg of caffeine or a salt thereof is inhaled by the
subject per inhalation. In some embodiments of the method, about 40
mg to about 50 mg of caffeine or a salt thereof is inhaled by the
subject per inhalation.
[0077] In some embodiments of the method, the composition further
comprises nicotine or a salt thereof. In some embodiments of the
method, less than 1 mg of nicotine is provided to a subject per
inhalation of any one of these compositions. For example, some
embodiments of the method, at least about 1, 2, 3, 4, 5, 6, 7, 8,
9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45
or 50 .mu.g, or an amount between any two of these values, of
nicotine or a salt thereof, is provided to the subject per
inhalation (i.e., vape).
[0078] In some embodiments of the method, the composition is
inhaled from the apparatus as a vapor comprising liquid droplets.
In some embodiments of the method, the droplets have an average
diameter of about 0.5, 1, 2.5 10, or 20 microns, or a diameter
between any two of these values.
[0079] In some embodiments of the method, the vapor is formed at
about 250.degree. F., 300.degree. F., 350.degree. F., 400.degree.
F., 450.degree. F., 500.degree. F., 550.degree. F., or a
temperature between any two of these values.
[0080] In one embodiment of the method, the apparatus is an
electronic vaporizer, such as an electronic cigarette. In one
embodiment of the method, the apparatus is any apparatus as
described herein.
[0081] In another aspect, a method of treatment is provided,
comprising: (a) aerosolizing any one of the inhalable compositions
or formulations comprised of caffeine, or a salt thereof, as
described herein, creating aerosolized droplets which are
sufficiently small as to enter the alveolar ducts; (b) allowing a
subject to inhale the aerosolized droplets of (a) thereby causing
caffeine, or a salt thereof, to enter the patient's blood at
air/blood diffusion membranes. In some embodiments, the method
further comprises: (c) repeating (a) and (b) a plurality of
times.
[0082] The present technology, thus generally described, will be
understood more readily by reference to the following examples,
which is provided by way of illustration and is not intended to
limit the present technology.
D. EXAMPLES
Example 1
Preparation of an Exemplary Inhalable Formulation of Caffeine
[0083] The substances listed in Table 1 are combined to form
"Inhalable Formulations A, B and C."
TABLE-US-00001 TABLE 1 Formulation Substances A B C caffeine HCl
100 mg 200 mg 300 mg yerba mate leaf extract 130 mg 130 mg 130 mg
huperzine A 50 mcg 50 mcg 50 mcg taurine 500 mg 500 mg 500 mg
inositol 500 mg 500 mg 500 mg niacinamide 30 mg 30 mg 30 mg
phenylalanine 500 mg 500 mg 500 mg citicoline 400 mg 400 mg 400 mg
citric acid (*optional) 200 mg 200 mg 200 mg peppermint (*optional)
200 mg 200 mg 200 mg lemon or orange 200 mg 200 mg 200 mg extract
(*optional) propylene glycol 400 mg 500 mg 600 mg vegetable
glycerol 600 mg 500 mg 400 mg de-ionized water 2,100 mg.sup. 2,000
mg.sup. 1,900 mg.sup. *subtract -200 mg of de-ionized water if
necessary for cartridge fit
Example 2
Vaporization of Inhalable Caffeine Formulations
[0084] The substances listed in Table 2 are combined with solvent
systems i-xi in Table 3 to form Inhalable Formulations D-N
Inhalable Formulations D-N are allowed to stand at room temperature
for 24 hours and examined for signs of precipitation or
emulsification. Inhalable Formulations D-N are then added to an
electronic vaporizer (e.g., electronic cigarette) known in the art
or as described herein. Each of Formulations D-N is separately
vaporized in a quantity that simulates a "vape" i.e., the amount of
vapor that will be inhaled by a subject from an electronic
vaporizer. The resulting vapors are captured. The captured vapors
are diluted with water, the caffeine is precipitated from solution,
collected and quantified. It is contemplated that some or all of
Formulations D-N will deliver at least 0.0001 mg of caffeine or a
salt thereof per vape.
TABLE-US-00002 TABLE 2 Substances Amount caffeine HCl 200 mg yerba
mate leaf extract 130 mg huperzine A 50 mcg taurine 500 mg inositol
500 mg niacinamide 30 mg phenylalanine 500 mg citicoline 400 mg
citric acid (* optional) 200 mg peppermint (* optional) 200 mg
lemon or orange 200 mg extract (* optional) propylene glycol *
vegetable glycerol * de-ionized water 2,000 mg.sup. * propylene
glycol + vegetable glycerol = 1,000 mg
TABLE-US-00003 TABLE 3 Solvent Propylene Vegetable System Glycol
Glycerol Formulation * i 0 mg 1,000 mg.sup. D ii 100 mg 900 mg E
iii 200 mg 800 mg F iv 300 mg 700 mg G v 400 mg 600 mg H vi 500 mg
500 mg I vii 600 mg 400 mg J viii 700 mg 300 mg K ix 800 mg 200 mg
L x 900 mg 100 mg M xi 1,000 mg.sup. 0 mg N * Upon combination with
the substances of Table 2.
Example 3
Single-Dose Application of Inhalable Caffeine Formulations
[0085] An electronic vaporizer (e.g., electronic cigarette) known
in the art or described herein may be used to deliver single-bolus
doses of Inhalable Composition B to healthy adults. A substantially
uniform aerosol is created when the Inhalable Composition B
solution is vaporized by the electronic vaporizer. The fine aerosol
that is generated allows the deep-lung deposition needed to achieve
rapid and efficient absorption of caffeine.
[0086] Methods: Eighteen healthy, adults are enrolled in a
randomized, open-label, multiple-exposure study which is conducted
in two parts. Two subjects are removed prior to Study Part 2 with
sixteen subjects starting and completing Study Part 2. Subjects'
ages may range, for example from about 19-41 years.
[0087] In Study Part 1, the tolerability and safety of Inhalable
Formulation B is evaluated. In Study Part 2, subjects received one
of three caffeine concentrations (from Formulations A, B and C),
delivering various bolus caffeine lung doses. Measures of arterial
caffeine plasma concentration and post-dosing alertness self-scores
(over a 10-point scale) are made following a single inhalation of
caffeine.
[0088] Results: It is anticipated that no clinically significant
changes in safety measures will be noted following dosing (vital
signs, ECG, spirometry, labs). Adverse events (AEs), if any, are
expected to be mild or moderate and self-resolvable without
medication.
[0089] Pharmacokinetics: Arterial plasma caffeine pharmacokinetics
are contemplated to demonstrate a rapid onset (T.sub.max=about 1
min) and substantial peak plasma concentrations. Maximum plasma
concentrations (C.sub.max) and area under the concentration-time
curves (AUC) are contemplated to consistent with a trend toward
dose proportionality.
[0090] Alertness: Patients are asked to rate their alertness on a
scale of 0 to 10 pre- and post-dosing. Subjects are anticipated to
report an increase in alertness post-dosing relative to pre-dosing.
A mean increase in alertness from baseline can be calculated for
all three dose levels.
[0091] Conclusions: It is contemplated that pulmonary
administration of the inhalable formulations of caffeine, described
herein, via an electronic vaporizer (e.g., electronic cigarette)
known in the art or described herein will be safe and tolerable.
The electronic vaporizer is expected to deliver inhaled caffeine
with a PK profile that is consistent with the rapid delivery and
absorption, and alertness in subjects is expected to increase
post-dosing.
E. EQUIVALENTS
[0092] The present disclosure is not to be limited in terms of the
particular embodiments described in this application. Many
modifications and variations can be made without departing from its
spirit and scope, as will be apparent to those skilled in the art.
Functionally equivalent methods, processes and compositions within
the scope of the disclosure, in addition to those enumerated
herein, will be apparent to those skilled in the art from the
foregoing descriptions. Such modifications and variations are
intended to fall within the scope of the appended claims. The
present disclosure is to be limited only by the terms of the
appended claims, along with the full scope of equivalents to which
such claims are entitled. It is to be understood that this
disclosure is not limited to particular methods, processes,
reagents, compounds compositions or biological systems, which can
of course vary. It is also to be understood that the terminology
used herein is for the purpose of describing particular embodiments
only, and is not intended to be limiting.
[0093] As used herein, "about" will be understood by persons of
ordinary skill in the art and will vary to some extent depending
upon the context in which it is used. If there are uses of the term
which are not clear to persons of ordinary skill in the art, given
the context in which it is used, "about" will mean up to plus or
minus 10% of the particular term.
[0094] The use of the terms "a" and "an" and "the" and similar
referents in the context of describing the elements (especially in
the context of the following claims) are to be construed to cover
both the singular and the plural, unless otherwise indicated herein
or clearly contradicted by context. Recitation of ranges of values
herein are merely intended to serve as a shorthand method of
referring individually to each separate value falling within the
range, unless otherwise indicated herein, and each separate value
is incorporated into the specification as if it were individually
recited herein. All processes described herein can be performed in
any suitable order unless otherwise indicated herein or otherwise
clearly contradicted by context. The use of any and all examples,
or exemplary language (e.g., "such as") provided herein, is
intended merely to better illuminate the embodiments and does not
pose a limitation on the scope of the claims unless otherwise
stated. No language in the specification should be construed as
indicating any non-claimed element as essential.
[0095] The embodiments, illustratively described herein may
suitably be practiced in the absence of any element or elements,
limitation or limitations, not specifically disclosed herein. Thus,
for example, the terms "comprising," "including," "containing,"
etc. shall be read expansively and without limitation.
Additionally, the terms and expressions employed herein have been
used as terms of description and not of limitation, and there is no
intention in the use of such terms and expressions of excluding any
equivalents of the features shown and described or portions
thereof, but it is recognized that various modifications are
possible within the scope of the claimed technology. Additionally,
the phrase "consisting essentially of" will be understood to
include those elements specifically recited and those additional
elements that do not materially affect the basic and novel
characteristics of the claimed technology. The phrase "consisting
of" excludes any element not specified.
[0096] In addition, where features or aspects of the disclosure are
described in terms of Markush groups, those skilled in the art will
recognize that the disclosure is also thereby described in terms of
any individual member or subgroup of members of the Markush
group.
[0097] As will be understood by one skilled in the art, for any and
all purposes, particularly in terms of providing a written
description, all ranges disclosed herein also encompass any and all
possible subranges and combinations of subranges thereof. Any
listed range can be easily recognized as sufficiently describing
and enabling the same range being broken down into at least equal
halves, thirds, quarters, fifths, tenths, etc. As a non-limiting
example, each range discussed herein can be readily broken down
into a lower third, middle third and upper third, etc. As will also
be understood by one skilled in the art all language such as "up
to," "at least," "greater than," "less than," and the like, include
the number recited and refer to ranges which can be subsequently
broken down into subranges as discussed above. Finally, as will be
understood by one skilled in the art, a range includes each
individual member.
[0098] All publications, patent applications, issued patents, and
other documents referred to in this specification are herein
incorporated by reference as if each individual publication, patent
application, issued patent, or other document was specifically and
individually indicated to be incorporated by reference in its
entirety. Definitions that are contained in text incorporated by
reference are excluded to the extent that they contradict
definitions in this disclosure.
[0099] While certain embodiments have been illustrated and
described, it should be understood that changes and modifications
could be made therein in accordance with ordinary skill in the art
without departing from the technology in its broader aspects as
defined in the following claims.
* * * * *