Note: Descriptions are shown in the official language in which they were submitted.
WO 2022/100805
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1
NICOTINE POUCH COMPOSITION
FIELD OF INVENTION
The present invention relates to pouch compositions and an oral pouched
nicotine
product according to the claims.
BACKGROUND
Delivery of nicotine by smoking has many well-known drawbacks, in particular
health
related problems, such as inclusion of carcinogenic substances.
However, tobacco substitutes also suffer from disadvantages, such as
inadequate relief
of cravings for the user.
A further challenge in the prior art is that the desired release of nicotine
should be
attractive to the user of the pouch from a user perspective.
Yet at further challenge in relation to the prior art may be that pouches as
delivery
vehicle for nicotine may be somewhat costly and thereby impose restrictions on
the
way pouches are designed in order to keep manufacturing costs in check.
It is an object of one embodiment of the present invention to provide a
nicotine
containing pouch, e.g. as a tobacco substitute, which may solve the above
problems.
SUMMARY
The present invention relates to a pouch composition comprising
a nicotine-ion exchange resin combination,
water in an amount of at least 15% by weight of the pouch composition, and
inorganic divalent cations.
One advantage of the present invention may be that a relatively high stability
of the
provided nicotine may be obtained, while at the same time obtaining a
relatively fast
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nicotine release. Obtaining a high stability may lead to nicotine being bound
too
effectively e.g. to a carrier and therefore lead to slow release. By means of
the claimed
pouch composition, including combination of a water content of at least 15% by
weight
of the composition and divalent inorganic cations, a high stability yet fast
release is
facilitated, while also having a very desirable mouthfeel and taste. The high
water
content facilitates effective release of nicotine during use.
One advantage of the invention is that a relatively fast release rate of
nicotine from the
pouch composition may be obtained due to the presence of the divalent cations.
At the
same time a desirable moist mouthfeel is provided, due to the high water
content,
which also facilitate fast nicotine release.
Furthermore, the invention may advantageously provide a more effective release
of
nicotine during use of a pouch comprising the pouch composition. Obtaining an
effective release of nicotine may enable a lower total dose of nicotine with
the same
amount of nicotine released, due to a minimization of any residual nicotine
not released
from the pouch composition.
In an advantageous embodiment of the invention, the solid oral nicotine
formulation comprises inorganic divalent cations in molar ratio of at least
0.1 relative
to the amount of nicotine in the nicotine-ion exchange resin combination, such
as at
least 0.25 relative to the amount of nicotine in the nicotine-ion exchange
resin
combination, such as at least 0.5 relative to the amount of nicotine in the
nicotine-ion
exchange resin combination.
In an advantageous embodiment of the invention, the pouch composition
comprises
inorganic divalent cations in molar ratio of at least 0.1 relative to the
amount
of nicotine in the nicotine-ion exchange resin combination, such as at
least 0.25 relative to the amount of nicotine in the nicotine-ion exchange
resin
combination, such as at least 0.5 relative to the amount of nicotine in the
nicotine-ion
exchange resin combination.
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The amount of divalent cations should advantageously be high enough to enable
ion-
exchange of the complexed nicotine for the divalent cations during use of a
pouch
comprising the pouch composition.
Furthermore, the amount of inorganic divalent cations may advantageously
also decrease the probability of exchanged nicotine from re-complexing with
the ion-
exchange resin, simply by occupying binding sites on the ion-exchange resin
during
use.
In an embodiment of the invention the amount of inorganic divalent cations may
even
prevent exchanged nicotine from re-complexing with the ion-exchange resin
during
use.
Also, the amount of inorganic divalent cations may decrease the probability of
any un-
complexed nicotine, such as free base nicotine and/or exchanged nicotine from
complexing/re-complexing with the ion-exchange resin during use.
In an advantageous embodiment of the invention, the solid oral nicotine
formulation comprises inorganic divalent cations in a molar ratio of at most
6.5
relative to the amount of nicotine in the nicotine-ion exchange resin
combination, such
as at most 6 relative to the amount of nicotine in the nicotine-ion exchange
resin
combination, such as at most 5 relative to the amount of nicotine in the
nicotine-ion
exchange resin combination, such as at most 3.75 relative to the amount of
nicotine in
the nicotine-ion exchange resin combination, such as at most 2.5 relative to
the amount
of nicotine in the nicotine-ion exchange resin combination.
In an advantageous embodiment of the invention, the pouch composition
comprises
inorganic divalent cations in a molar ratio of at most 5 relative to the
amount
of nicotine in the nicotine-ion exchange resin combination, such as at most
3.75
relative to the amount of nicotine in the nicotine-ion exchange resin
combination, such
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as at most 2.5 relative to the amount of nicotine in the nicotine-ion exchange
resin
combination.
One advantage of the above embodiment may be that including inorganic divalent
cations in a not too high amount facilitates a desirable taste and mouthfeel,
by avoiding
or minimizing undesirable taste and/or mouthfeel, such as undesired salty
taste, a local
dehydration or even an oral dehydrating sensation.
In an embodiment of the invention the pouch composition comprises inorganic
divalent cations in a molar ratio of between 0.1 and 6.5 relative to the
amount of
nicotine in the nicotine-ion exchange resin combination, such as 0.1 and 6.0
relative
to the amount of nicotine in the nicotine-ion exchange resin combination, such
as 0.1
and 5.0 relative to the amount of nicotine in the nicotine-ion exchange resin
combination, such as between 0.1 and 4.0 relative to the amount of nicotine in
the
nicotine-ion exchange resin combination, such as between 0.1 and 3.0 relative
to the
amount of nicotine in the nicotine-ion exchange resin combination, such as
between
0.1 and 2.0 relative to the amount of nicotine in the nicotine-ion exchange
resin
combination, such as between 0.1 and 1.0 relative to the amount of nicotine in
the
nicotine-ion exchange resin combination.
In an embodiment of the invention the pouch composition comprises inorganic
divalent cations in a molar ratio of between 0.1 and 5.0 relative to the
amount of
nicotine in the nicotine-ion exchange resin combination, such as between 0.5
and 5.0
relative to the amount of nicotine in the nicotine-ion exchange resin
combination, such
as between 0.75 and 5.0 relative to the amount of nicotine in the nicotine-ion
exchange
resin combination, such as between 1.0 and 4.0 relative to the amount of
nicotine in
the nicotine-ion exchange resin combination, such as between 2.0 and 4.0
relative to
the amount of nicotine in the nicotine-ion exchange resin combination.
In an embodiment of the invention the pouch composition comprises inorganic
divalent cations in a molar ratio of between 0.01 and 5.0 relative to the
amount of
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nicotine in the nicotine-ion exchange resin combination, such as between 0.01
and 4.0
relative to the amount of nicotine in the nicotine-ion exchange resin
combination, such
as between 0.01 and 3.0 relative to the amount of nicotine in the nicotine-ion
exchange
resin combination, such as between 0.01 and 2.0 relative to the amount of
nicotine in
5 the nicotine-ion exchange resin combination, such as between
0.01 and 1.0 relative to
the amount of nicotine in the nicotine-ion exchange resin combination.
Here, the molar ratio refers to the molar content of divalent cations divided
by the
molar content of nicotine.
In an advantageous embodiment of the invention, the inorganic divalent cations
are
selected from the group consisting of divalent cations of calcium, magnesium,
iron,
zinc, and any combination thereof.
In an advantageous embodiment of the invention, the inorganic divalent cations
are
selected from the group consisting of divalent cations of calcium and
magnesium.
In an embodiment of the invention, the inorganic divalent cations are provided
as a
salt comprising inorganic or organic anions.
In an advantageous embodiment of the invention, the inorganic divalent cations
are
provided as a salt comprising anions selected from the group consisting of
carboxylates, such as acetate, lactate, oxalate, propionate, or levulinate,
organic
sulfonate, organic sulfate, organic phosphate, chloride, bromide, nitrate ,
sulfate,
hydrogen phosphate, oxide, and any combination thereof.
In an embodiment of the invention the inorganic divalent cations are provided
as a salt
in an amount of between 0.1 and 15.0% by weight of the composition, such as
between
0.1 and 10.0% by weight of the composition, such as between 0.5 and 10.0% by
weight
of the composition.
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In an embodiment of the invention, the organic anions are selected from the
group
consisting of carboxylates, such as acetate, lactate, oxalate, propionate,
levulinate;
organic sulfonate; organic sulfate; organic phosphate; and any combination
thereof
In an advantageous embodiment of the invention, the inorganic divalent cations
are
provided as an inorganic salt.
In an advantageous embodiment of the invention, the inorganic divalent cations
are
provided as an inorganic salt in an amount of between 0.1 and 15.0% by weight
of the
composition, such as between 0.1 and 10.0% by weight of the composition, such
as
between 0.5 and 10.0% by weight of the composition.
In an embodiment of the invention the inorganic divalent cations are provided
as an
inorganic salt in the amount of between 0.1 and 15.0% by weight of the
composition,
such as between 0.1 and 10.0% by weight of the composition, such as between
0.5 and
10.0% by weight of the composition.
In an embodiment of the invention the inorganic divalent cations are provided
as an
inorganic salt in the amount of between 0.1 and 15.0% by weight of the
composition,
such as between 0.1 and 10.0% by weight of the composition, such as between
0.5 and
7.0% by weight of the composition, such as between 0.1 and 7.0% by weight of
the
composition, such as between 0.5 and 5.00/0 by weight of the composition, such
as
between 0.5 and 4.0% by weight of the composition.
In an advantageous embodiment of the invention, inorganic divalent cations are
provided as an inorganic salt comprising inorganic anions selected from the
group
consisting of chloride, bromide, nitrate, sulfate, hydrogen carbonate,
hydrogen
phosphate, oxide, hydroxide, and any combination thereof
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It is noted that in some embodiments, the inorganic anions may be combined
e.g. such
that the cations form separate salts with two different types of anions. One
example
could e.g. be magnesium chloride combined with magnesium bromide.
In an advantageous embodiment of the invention, wherein the inorganic divalent
cations are provided as an inorganic salt comprising inorganic anions are
selected from
the group consisting of chloride, bromide, sulfate, hydrogen carbonate, and
any
combination thereof.
In an advantageous embodiment of the invention, wherein the inorganic divalent
cations are provided as an inorganic salt comprising inorganic anions are
selected from
the group consisting of chloride, bromide, sulfate, and any combination
thereof
In an advantageous embodiment of the invention, wherein the inorganic divalent
cations are provided as an inorganic salt comprising inorganic anions are
selected from
the group consisting of chloride, bromide, and any combination thereof
In an advantageous embodiment of the invention, the inorganic anions comprise
chloride.
In an embodiment of the invention, the inorganic cations are magnesium and/or
calcium and the anions comprise chloride.
In an embodiment of the invention, the inorganic anions are chloride.
In an embodiment of the invention, the inorganic cations are magnesium and/or
calcium and the anions are chloride.
In an advantageous embodiment of the invention, the inorganic divalent cations
are
provided as an inorganic salt selected from the group consisting of calcium
chloride or
magnesium chloride, or combinations thereof
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In an embodiment of the invention, the divalent cations are provided as a
pharmaceutically acceptable salt.
In an embodiment of the invention, the divalent cations are provided as a
pharmaceutically acceptable inorganic salt.
In an embodiment of the invention the inorganic divalent cations are provided
as a
hydrated salt.
In an embodiment of the invention the inorganic divalent cations are provided
as a
hydrated inorganic salt.
In an embodiment of the invention, the divalent cations are provided as an
alimentary
acceptable salt.
In an embodiment of the invention, the divalent cations are provided as an
alimentary
acceptable inorganic salt.
In an advantageous embodiment of the invention, the divalent cations are
provided as
a water-soluble salt having a water-solubility of at least 5 gram per 100 mL
of water
measured at 25 degrees Celsius, atmospheric pressure and pH 7Ø
With atmospheric pressure is understood a pressure around 101.3 1cPa or a
pressure
within the range of 90 to 110 kPa.
In an embodiment of the invention the pouch composition comprises inorganic
divalent cations provided as a water-soluble salt, wherein the pouch
composition
comprises said inorganic divalent cations provided as a water-soluble salt in
a molar
ratio of between 0.1 and 6.5 relative to the amount of nicotine in the
nicotine-ion
exchange resin combination, such as 0.1 and 6.0 relative to the amount of
nicotine in
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the nicotine-ion exchange resin combination, such as 0.1 and 5.0 relative to
the amount
of nicotine in the nicotine-ion exchange resin combination, such as between
0.1 and
4.0 relative to the amount of nicotine in the nicotine-ion exchange resin
combination,
such as between 0.1 and 3.0 relative to the amount of nicotine in the nicotine-
ion
exchange resin combination, such as between 0.1 and 2.0 relative to the amount
of
nicotine in the nicotine-ion exchange resin combination, such as between 0.1
and 1.0
relative to the amount of nicotine in the nicotine-ion exchange resin
combination.
In an embodiment of the invention the inorganic divalent cations are provided
as a
water-soluble salt in the amount of between 0.1 and 15.0% by weight of the
composition.
In an embodiment of the invention, the divalent cations are provided as an
inorganic
and water-soluble salt having a water-solubility of at least 5 gram per 100 mL
of water
measured at 25 degrees Celsius, atmospheric pressure and pH 7Ø
In an embodiment of the invention the inorganic divalent cations are provided
as a
water-soluble salt in the amount of between 0.1 and 15.0% by weight of the
composition, such as between 0.1 and 10.0% by weight of the composition, such
as
between 0.5 and 7.0% by weight of the composition, such as between 0.1 and
7.0% by
weight of the composition, such as between 0.5 and 5.0% by weight of the
composition, such as between 0.5 and 4.0% by weight of the composition.
In an embodiment of the invention the pouch composition comprises inorganic
divalent cations provided as an inorganic, water-soluble salt, wherein the
pouch
composition comprises said inorganic divalent cations provided as an
inorganic, water-
soluble salt in a molar ratio of between 0.1 and 6.5 relative to the amount of
nicotine
in the nicotine-ion exchange resin combination, such as 0.1 and 6.0 relative
to the
amount of nicotine in the nicotine-ion exchange resin combination, such as 0.1
and 5.0
relative to the amount of nicotine in the nicotine-ion exchange resin
combination, such
as between 0.1 and 4.0 relative to the amount of nicotine in the nicotine-ion
exchange
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resin combination, such as between 0.1 and 3.0 relative to the amount of
nicotine in
the nicotine-ion exchange resin combination, such as between 0.1 and 2.0
relative to
the amount of nicotine in the nicotine-ion exchange resin combination, such as
between 0.1 and 1.0 relative to the amount of nicotine in the nicotine-ion
exchange
5 resin combination.
In an embodiment of the invention the inorganic divalent cations are provided
as an
inorganic and water-soluble salt in the amount of between 0.1 and 15.0% by
weight of
the composition, such as between 0.1 and 10.0% by weight of the composition,
such
10 as between 0.5 and 7.0% by weight of the composition, such as
between 0.1 and 7.0%
by weight of the composition, such as between 0.5 and 5.0% by weight of the
composition, such as between 0.5 and 4.0% by weight of the composition.
With provided is here understood, that the inorganic cations are added to the
composition as a salt.
By providing the divalent cations as a water-soluble salt, the dissolution of
the salt into
cations could advantageously be faster and more effective, whereby relative
fast
release of nicotine could be achieved.
In an advantageous embodiment of the invention, the pouch composition
comprises
nicotine in an amount of at least 0.1% by weight, such as least 0.2% by weight
of the
pouch composition.
In an embodiment of the invention, the pouch composition comprises nicotine in
an
amount of 0.1 to 5.0% by weight of the pouch composition, such as 0.2 to 4.0%
by
weight of the pouch composition, such as 1.0 to 2.0% by weight of the pouch
composition.
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The pouch composition should have a desirable content of nicotine able to
provide the
user with a desirable dose of nicotine, while also providing the user with a
desirable
volume of composition being enclosed in the pouch.
In an advantageous embodiment of the invention, the pouch composition
comprises
nicotine-ion exchange combination in an amount of 0.1 to 20% by weight of the
pouch
composition.
It is understood here, that the divalent cations does not form part of the
nicotine-ion
exchange combination when preparing the pouch composition. If combined before
preparation of the pouch composition. A pre-combination may cause stability
issues,
since the divalent cations could induce a too early release of nicotine from
the ion-
exchange resin. This could in particular be a problem, when incorporating a
such
combination into a pouch composition having a high water content, such as at
least
15% by weight of the pouch composition.
In an embodiment of the invention, the divalent cations are not included in
the
provided nicotine-ion-exchange combination.
In an embodiment of the invention, the nicotine-ion-exchange combination does
not
comprise divalent cations.
In an embodiment of the invention, the divalent cations are provided as a
salt.
In an embodiment of the invention, the pouch composition comprises nicotine-
ion
exchange combination in an amount of 0.1 to 20% by weight of the pouch
composition,
such as 1.0 to 15% by weight of the pouch composition, such as 3.0 to 15% by
weight
of the pouch composition, such as 5.0 to 15% by weight of the pouch
composition.
In an embodiment of the invention, the pouch composition comprises nicotine-
ion
exchange combination in an amount of 0.1 to 20% by weight of the pouch
composition,
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such as 1.0 to 15% by weight of the pouch composition, such as 1.0 to 10% by
weight
of the pouch composition, such as 3.0 to 10% by weight of the pouch
composition.
In an advantageous embodiment of the invention, the nicotine-ion exchange
resin
combination comprises nicotine in an amount of between 5 and 50% by weight.
In an embodiment of the invention the nicotine-ion exchange resin combination
comprises nicotine complexed with ion exchange resin, wherein the nicotine
constitutes an amount of between 5 and 50% by weight of nicotine-ion exchange
resin
combination.
In an embodiment of the invention the nicotine-ion exchange resin combination
consists of nicotine complexed with ion exchange resin, wherein the nicotine
constitutes an amount of between 10 and 50% by weight of nicotine-ion exchange
resin
combination, such as between 10 and 40% by weight of nicotine-ion exchange
resin
combination, such as. between 10 and 30% by weight of nicotine-ion exchange
resin
combination, such as between 10 and 25% by weight of nicotine-ion exchange
resin
combination.
In an embodiment of the invention the nicotine-ion exchange resin combination
comprises free-base nicotine mixed with ion exchange resin, wherein the
nicotine
constitutes an amount of between 5 and 50% by weight of nicotine-ion exchange
resin
combination.
In an embodiment of the invention the nicotine-ion exchange resin combination
comprises free-base nicotine mixed with ion exchange resin, wherein the
nicotine
constitutes an amount of between 5 and 50% by weight of nicotine-ion exchange
resin
combination, such as between 10 and 50% by weight of nicotine-ion exchange
resin
combination, such as between 20 and 50% by weight of nicotine-ion exchange
resin
combination, such as between 25 and 50% by weight of nicotine-ion exchange
resin
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combination, such as between 25 and 45% by weight of nicotine-ion exchange
resin
combination.
In an embodiment of the invention the nicotine-ion exchange resin combination
comprises free-base nicotine mixed with ion exchange resin, wherein the
nicotine
constitutes an amount of between 5 and 40% by weight of nicotine-ion exchange
resin
combination, such as between 10 and 40% by weight of nicotine-ion exchange
resin
combination, such as between 10 and 35% by weight of nicotine-ion exchange
resin
combination, such as between 10 and 25% by weight of nicotine-ion exchange
resin
combination, such as between 10 and 15% by weight of nicotine-ion exchange
resin
combination.
In an advantageous embodiment of the invention, the nicotine-ion exchange
resin
combination comprises nicotine in an amount of between 5 and 50% by weight and
ion-exchange resin in an amount between 10 and 95% by weight.
In an embodiment of the invention the nicotine-ion exchange resin combination
comprises nicotine in an amount of between 5 and 50% by weight and ion-
exchange
resin in an amount between 10 and 95% by weight.
In an embodiment of the invention the nicotine-ion exchange resin combination
comprises nicotine in an amount of between 10 and 30% by weight and ion-
exchange
resin in an amount between 20 and 90% by weight.
In an embodiment of the invention the nicotine-ion exchange resin combination
consist
of nicotine in an amount of between 10 and 30% by weight and ion-exchange
resin in
an amount between 70 and 90% by weight.
In an embodiment of the invention the nicotine-ion exchange resin combination
is
substantially free of water.
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In an embodiment of the invention the nicotine-ion exchange resin combination
further
comprising a C3 sugar alcohol.
In an embodiment, the C3 sugar alcohol may be selected from glycerol,
propylene
glycol, and any combination thereof.
In an embodiment of the invention the nicotine-ion exchange resin combination
further
comprises glycerol.
In an embodiment of the invention, the nicotine-ion exchange resin combination
further comprises glycerol in an amount of 0.1 to 50% by weight, such as 5 to
40% by
weight, such as 5 to 30% by weight.
In an embodiment of the invention the nicotine-ion exchange resin combination
comprises nicotine in an amount of between 5 and 50% by weight and ion-
exchange
resin in an amount between 20 and 75% by weight.
In an embodiment of the invention the nicotine-ion exchange resin combination
comprises water in an amount of no more than 75% by weight, such as no more
than
50% by weight, such as no more than 40% by weight, such as no more than 30% by
weight, such as no more than 20% by weight, such as no more than 10% by
weight,
such as no more than 5% by weight.
In an advantageous embodiment of the invention, the ion exchange resin
comprises
one or more resin(s) selected from the group consisting of:
(i) a methacrylic, weakly acidic type of resin containing carboxylic
functional groups,
(ii) a copolymer of methacrylic acid and divinylbenzene, said copolymer
containing
carboxylic functional groups,
(iii) a polystyrene, strongly acidic type of resin containing sulphonic
functional groups,
(iv) a polystyrene, intermediate acidic type of resin containing phosphonic
functional
groups, and
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(v) a combination thereof.
In an advantageous embodiment of the invention, the ion exchange resin
comprises
polacrilex resin.
5
In an advantageous embodiment of the invention, the ion exchange resin is
polacrilex
resin.
In an embodiment of the invention, the ion exchange resin is polacrilex resin.
In an embodiment of the invention, the polacrilex resin comprises or is
AmberlitegIRP64.
In an advantageous embodiment of the invention, the nicotine-ion exchange
resin
combination comprises nicotine complexed with ion exchange resin.
In an advantageous embodiment of the invention, the nicotine-ion exchange
resin
combination is nicotine complexed with ion exchange resin.
Thus, in the above embodiment the nicotine-ion exchange resin combination
consists
of nicotine complexed with ion exchange resin.
In an advantageous embodiment of the invention, the nicotine-ion exchange
resin
combination comprises free-base nicotine mixed with ion exchange resin.
One advantage of the above embodiment may be providing sustained release of
nicotine. At the same time, the release rate of nicotine is not too slow to
give the user
the craving relief desired.
In an embodiment of the invention, the nicotine-ion exchange resin combination
is
free-base nicotine mixed with ion exchange resin.
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In an embodiment of the invention the pouch composition comprises further
nicotine.
In an embodiment of the invention the pouch composition comprises further
nicotine.
In an embodiment of the invention the pouch composition comprises further
nicotine
selected from the group consisting of a nicotine salt, nicotine free base,
nicotine bound
to an ion exchanger, such as an ion exchange resin, such as nicotine
polacrilex resin, a
nicotine inclusion complex or nicotine in any non-covalent binding; nicotine
bound to
zeolites; nicotine bound to cellulose, such as microcrystalline cellulose, or
starch
microspheres, and mixtures thereof.
In an advantageous embodiment of the invention, the pouch composition
comprises
water in an amount of 15-65% by weight of the composition, such as 15-60% by
weight of the composition, such as 15-50% by weight of the composition, such
as 20-
50% by weight of the composition, such as 20-40% by weight of the composition,
such
as 25-40% by weight of the composition, such as 25-35% % by weight of the
composition.
In an embodiment of the invention, the pouch composition comprises water in an
amount of 15-65% by weight of the composition, such as 20-65% by weight of the
composition, such as 25-65% by weight of the composition.
In an embodiment of the invention, the pouch composition comprises water in an
amount of 15-65% by weight of the composition, such as 15-60% by weight of the
composition, such as 15-50% by weight of the composition, such as 15-40% by
weight
of the composition.
In an embodiment of the invention, the pouch composition comprises water in an
amount of 15-60% by weight of the composition, such as 15-50% by weight of the
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composition, such as 15-40% by weight of the composition, such as 15-30% by
weight
of the composition.
In an embodiment of the invention, the pouch composition comprises water in an
amount of 15-40% by weight of the composition.
The water may be added as a separate component to be fully or partly mixed
into other
components, such as fibers. E.g. when adding a nicotine ion-exchange
combination
consisting of a mixture of free base nicotine with ion exchange resin and
water, a
significant amount of water of the final pouch composition may come from the
this
mixture. For example, if the final amount pouch composition comprises 5% water
from
the nicotine-ion exchange resin combination, then up to one third of the water
in the
pouch composition derives from the nicotine-ion exchange resin combination.
In an advantageous embodiment of the invention, the pouch composition
comprises at
least one sugar alcohol.
In an embodiment of the invention, xylitol, maltitol, mannitol, erythritol,
isomalt,
sorbitol, lactitol, and mixtures thereof is used as the at least one sugar
alcohol. The at
least one sugar alcohol may also comprise further sugar alcohols. As an
example
embodiment, hydrogenated starch hydrolysates may be used, which comprises a
mixture of sorbitol, maltitol and further sugar alcohols.
Sugar alcohols may advantageously facilitate and induce salivation of the
pouch
composition, whereby dissolution of the inorganic divalent cations are
achieved, and
release of nicotine is obtained, such as release of nicotine from the ion-
exchange resin
and release of nicotine from the pouch.
Sugar alcohols may advantageously be used to further increase the nicotine
release
from the pouch.
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Also, sugar alcohols may advantageously be used for obtaining a desirable
mouthfeel
by increasing salivation and thereby counteract any local dehydration or oral
dehydrating sensation experienced by the user of the pouch.
Thus, sugar alcohol may advantageously be used in combination with inorganic
divalent cations in order to achieve a desirable release of nicotine, while
also a
desirable taste is achieved.
In an embodiment of the invention, the at least one sugar alcohol is selected
from sugar
alcohols having at least 4 carbon atoms.
In an advantageous embodiment of the invention, the at least one sugar alcohol
is
selected from xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol,
lactitol, and
mixtures thereof.
In an advantageous embodiment of the invention, the pouch composition
comprises at
least two sugar alcohols.
It is noted that different sugar alcohols may be applied for the purpose of
taste and
salivation, where the sugar alcohol composition is made of different sugar
alcohols
having different properties with respect to storage, bacteria growth,
processability
and/or taste.
In an embodiment of the invention, the at least two sugar alcohols are
selected from
xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and
mixtures thereof.
In an advantageous embodiment of the invention, the pouch composition
comprises
sugar alcohol in an amount of at least 1% by weight of the composition, such
as at
least 2% by weight of the composition, such as at least 5% by weight of the
composition, such as at least 10% by weight of the composition, such as at
least 15%
by weight of the composition.
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In an advantageous embodiment of the invention, the pouch composition
comprises
sugar alcohol in an amount of 1 to 80% by weight of the composition, such as 2
to
700/0 by weight of the composition, such as 5 to 60% by weight of the
composition,
such as 10 to 50% by weight of the composition, such as 15 to 50% by weight of
the
composition.
In an embodiment of the pouch composition comprises sugar alcohol in an amount
of
1 to 80% by weight of the composition, such as 2 to 70% by weight of the
composition,
such as 5 to 60% by weight of the composition, such as 10 to 50% by weight of
the
composition, such as 15 to 50% by weight of the composition.
In an embodiment of the pouch composition comprises sugar alcohol in an amount
of
1 to 80% by weight of the composition, such as 10 to 70% by weight of the
composition, such as 10 to 60% by weight of the composition, such as 15 to 60%
by
weight of the composition, such as 20 to 60% by weight of the composition,
such as
to 50% by weight of the composition.
In an advantageous embodiment of the invention, the pouch composition
comprises at
20 least one water-insoluble fiber.
In an advantageous embodiment of the invention, the pouch composition
comprises
said water-insoluble fiber in an amount between 5 and 50 % by weight of the
pouch
composition, such as 10-45% by weight of the pouch composition, such as 15-40%
by
weight of the pouch composition.
In an embodiment of the invention, the pouch composition comprises said water-
insoluble fiber in an amount between 5 and 50 % by weight of the pouch
composition,
such as 5-45% by weight of the pouch composition, such as 5-40% by weight of
the
pouch composition.
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In an embodiment of the invention, the pouch composition comprises said water-
insoluble fiber in an amount between 5 and 50 % by weight of the pouch
composition,
such as 10-50% by weight of the pouch composition, such as 15-50% by weight of
the
pouch composition.
5
An advantage of the above embodiment may be that a residue is left even after
use of
a nicotine pouch comprising the pouch composition. This may lead to a pleasant
perception for users of the nicotine pouch, e.g. due to similarity with
tobacco
containing products.
The water-insoluble fiber may advantageously provide a desirable mouthfeel
throughout the use of the pouch.
In an advantageous embodiment of the invention, the water-insoluble fiber is a
plant
fiber.
In an advantageous embodiment of the invention, the water-insoluble fiber is
selected
from wheat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato
fibers, barley
fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers,
cellulose fibers,
apple fibers, cocoa fibers, cellulose fibers, bran fibers, bamboo fibers,
powdered
cellulose, and combinations thereof.
Powdered cellulose within the scope of the invention is understood to be
cellulose
prepared by processing alpha-cellulose obtained as a pulp from strains of
fibrous plant
materials, such as wood pulp.
In an embodiment of the invention, the water-insoluble fiber comprises or
consists of
cereal fibers.
In an embodiment of the invention, the water-insoluble fiber comprises or
consists of
fruit and/or vegetable fibers.
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In an embodiment of the invention, the water-insoluble composition comprises
or
consists of water-insoluble fiber selected from wheat fibers, oat fibers, pea
fibers,
powdered cellulose, or combinations thereof.
In an embodiment of the invention, the water-insoluble fiber is selected from
wheat
fibers, oat fibers, pea fibers, powdered cellulose, or combinations thereof.
In an embodiment of the invention, the water-insoluble composition comprises
or
consists of water-insoluble fiber selected from wheat fibers, oat fibers, pea
fibers, or
combinations thereof.
In an embodiment of the invention, the water-insoluble fiber is selected from
wheat
fibers, oat fibers, pea fibers, or combinations thereof.
In an embodiment of the invention, the water-insoluble composition comprises
or
consists of water-insoluble fiber selected from wheat fibers, oat fibers, or
combinations
thereof.
In an embodiment of the invention, the water-insoluble fiber is selected from
wheat
fibers, oat fibers, or combinations thereof.
In an embodiment of the invention, the water-insoluble fiber is powdered
cellulose.
Non-limiting examples of usable water-insoluble fibers include Vitacel WF 600,
Vitacel HF 600, Vitacel P95, Vitacel WF 200, Vitacel LOO, Vitacel Erbsenfaser
EF
150, Vitacel bamboo fiberbaf 90, Vitacel HF 600, Vitacel Cellulose L700G,
Vitacel
PF200, Vitacel potatofiber KF200, Vitacel bamboo fiberhaf BAF40, Vitacel
Haferfaser/oat fiber HF-401-30 US.
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Non-limiting examples of usable powdered cellulose include Vitacel L 00,
Vitacel
Cellulose L700G, Vitacel LC1000, Vitacel L600-20, Vitacel L600 etc.
In an embodiment, the powdered cellulose is chemically unmodified. Thus,
powdered
cellulose may be chemically unmodified cellulose fibers, which do not include
e.g.
microcrystalline cellulose (MCC).
In an advantageous embodiment of the invention, the water-insoluble fiber has
a water
binding capacity of at least 200%, such as at least 300%, such as at least
400%.
An advantage of the above embodiment may be that the high water-binding
capacity
enables pouch compositions having a high water-content.
Furthermore, the pouches having a high water-content where found to have a
desirable
texture and mouthfeel may while still being able to store manufactured pouches
together in abutment e.g. in cans etc. without sticking too much together to
result in
ruptures of the pouches when being removed.
Also, water-insoluble fibers having a high water-binding capacity may reduce
any
nicotine exchange induced by the divalent cations happening prior to the pouch
being
used.
Hence, pouches comprising water-insoluble fibers having a high water-binding
capacity could advantageously have a decreased relative standard deviation
(RSD) on
the nicotine content.
In an advantageous embodiment of the invention, the content of nicotine
between a
series of at least 10 oral pouches comprising said pouch composition holds a
relative
standard deviation (RSD) below 10%, preferably below 8%, more preferably at
most
6%, even more preferably at most 4%, most preferably at most 2%.
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In an embodiment of the invention, the content of the nicotine between a
series of at
least 10 oral pouches comprising said pouch composition holds a relative
standard
deviation (RSD) of 0.1 - 10%, preferably 0.1 - 8%, more preferably 0.1 - 6%,
even
more preferably 0.1 - 4%, and most preferably 0.1 ¨ 2%.
In an embodiment of the invention, the water-insoluble fiber has a water
binding
capacity of 300 to 1500%, such as 400 to 1300%.
In an embodiment of the invention, the water-insoluble fiber has a water
binding
capacity of 200% to 1500%, such as 300 to 1300%, such as 200 to 800%, such as
300
to 800%, such as 400 to 600%.
In an embodiment of the invention, the water-insoluble fiber has a water
binding
capacity of 200 to 1500%, such as 300 to 1300%, such as 300 to 900%, such as
300 to
700%, such as 400 to 700%.
In an embodiment of the invention, the water-insoluble fiber has a water
binding
capacity of 200 to 1500%, such as 400 to 1500%, such as 500 to 1500%, such as
500
to 1200%, such as 500 to 1000%.
In an embodiment of the invention, the water-insoluble fiber has a swelling
capacity
of at least 5.0 mL/g, such as 5.0 ¨ 20 mL/g.
An advantage of the above embodiment is that the amount of water-insoluble
fiber can
be reduced without compromising the mouthfeel during use. If an amount of
water-
insoluble fiber is substituted for a water-soluble component, the swelling of
the water-
insoluble fiber will during use counteract the dissolution of the water-
soluble
component, thereby the user will not experience any decrease in pouch content
during
use.
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In an embodiment of the invention, the water-insoluble fibers are selected
from pea
fibers, powdered cellulose, and combinations thereof, and wherein the pouch
composition comprises flavor in an amount of no more than 10% by weight of the
pouch composition.
In an embodiment of the invention, the pouch composition comprises water-
insoluble
fibers selected from pea fibers and powdered cellulose, or a combination
thereof, and
flavor in an amount of 0.01 - 10% by weight of the pouch composition.
In an advantageous embodiment of the invention, the water-insoluble fiber has
a
density of 50 to 500 gram per Liter, such as 100 to 400 gram per Liter, such
as 200 to
300 gram per Liter.
The use of water-insoluble fiber having a relatively low bulk density, will
provide not
only a good mouthfeel, but also an effective release from the pouch, due to
the fact
that a relatively low bulk density promotes effective salivation, thereby
dissolution and
release of water-soluble ingredients of the composition.
In an advantageous embodiment of the invention, the pouch composition
comprises a
pH regulating agent.
In an advantageous embodiment of the invention, the pouch composition
comprises
pH regulating agent in an amount between 0.01 and 15% by weight of the pouch
composition, such as between 0.5 and 10% by weight of the pouch composition,
such
as between 1 and 10% by weight of the pouch composition, such as between 5 and
10% by weight of the pouch composition.
Obtaining a relatively fast release rate of nicotine and an effective
uptake/absorption
may be desirable as this ensures a fast effect for the user, i.e. craving
relief.
Furthermore, the combination of having an effective release and an effective
absorption advantageously enables a relative high exploitation of the nicotine
dose
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within the pouch. Having a relative high exploitation of the nicotine dose
within the
pouch may further provide a reduction of necessary nicotine dose of the pouch,
without
compromising the resulting effect. A lower nicotine dose may in tern result in
a
reduction in production cost, as nicotine may be relatively expensive, but may
also
5 assist users who want to lower their intake of nicotine.
In an advantageous embodiment of the invention, the pH regulating agent is a
basic
pH regulating agent, such as a basic buffering agent.
10 In an advantageous embodiment of the invention, the p1-1
regulating agent is a buffering
agent, such as a basic buffering agent.
In an embodiment of the invention, the pH regulating agent is water-soluble.
15 In an embodiment of the invention, the pH regulating agent is
having water-solubility
of at least 5 gram per 100 mL of water measured at 25 degrees Celsius,
atmospheric
pressure and pH 7Ø
In an embodiment of the invention, the pouch composition is adapted to give a
pH of
20 at least 8.0, such as a pH of at least 9.0, when 2.0 gram of
pouch composition is added
to 20 mL of 0.02 M potassium di hydrogen phosphate-buffer (pH adjusted to
7.4).
An advantage of the above embodiment may be that a relatively effective uptake
of
nicotine is facilitated due to the high pH value obtained.
A further advantage of the above embodiment may be that the need for
preservative
may be decreased or even eliminated and that low amounts of such preservatives
may
be used if not absent.
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Also, the high pH value obtained may advantageously provide for a tingling
sensation
in the mouth which may be perceived as a desirable mouthfeel, e.g. due to
resemblance
with tobacco-based pouch products.
In an embodiment of the invention, the pH regulating agent is selected from
the group
consisting of Acetic acid, Adipic acid, Citric acid, Fumaric acid, Glucono-6-
lactone,
Gluconic acid, Lactic acid, Malic acid, Maleic acid, Tartaric acid, Succinic
acid,
Propionic acid, Ascorbic acid, Phosphoric acid, Sodium orthophosphate,
Potassium
orthophosphate, Calcium orthophosphate, Sodium diphosphate, Potassium
diphosphate, Calcium di phosphate, Pentasodium triphosphate, Pentapotassium
triphosphate, Sodium polyphosphate, Potassium polyphosphate, Carbonic acid,
Sodium carbonate, Sodium bicarbonate, Potasium carbonate, Calcium carbonate,
Magnesium carbonate, Magnesium oxide, or any combination thereof
In an embodiment of the invention, the pH regulating agent is selected from
the group
consisting of Acetic acid, Adipic acid, Citric acid, Fumaric acid, Glucono-6-
lactone,
Gluconic acid, Lactic acid, Malic acid, Maleic acid, Tartaric acid, Succinic
acid,
Propionic acid, Ascorbic acid, Phosphoric acid, Sodium orthophosphate,
Potassium
orthophosphate, Sodium diphosphate, Potassium diphosphate, Pentasodium
triphosphate, Pentapotassium triphosphate, Sodium polyphosphate, Potassium
polyphosphate, Carbonic acid, Sodium carbonate, Sodium bicarbonate, Potassium
carbonate, Magnesium carbonate, Magnesium oxide, or any combination thereof
In an advantageous embodiment of the invention, the pH regulating agent is
selected
from the group consisting Sodium carbonate, Sodium bicarbonate, Potassium
carbonate, and Magnesium carbonate; Potassium bicarbonate; trometamol;
phosphate
buffer, amino acids, or any combination thereof.
In an embodiment, the pouch composition comprises inorganic divalent cations,
which
may be provided as a water soluble salt, and in addition thereto a pH
regulating agent
selected from the group consisting Sodium carbonate, Sodium bicarbonate,
Potassium
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carbonate, and Magnesium carbonate; Potassium bicarbonate; trometamol;
phosphate
buffer; amino acids, or any combination thereof
In an embodiment, the pouch composition comprises inorganic divalent cations,
which
may be provided as a water soluble salt, and in addition thereto a pH
regulating agent
selected from the group consisting Sodium carbonate, Sodium bicarbonate,
Potassium
carbonate, and Magnesium carbonate; Potassium bicarbonate; trometamol;
phosphate
buffer; or any combination thereof
In an embodiment, the pouch composition comprises inorganic divalent cations,
which
may be provided as a water soluble salt, and in addition thereto a pH
regulating agent
selected from the group consisting Sodium carbonate, Sodium bicarbonate,
Potassium
carbonate, and Magnesium carbonate; Potassium bicarbonate; trometamol; or any
combination thereof
In the present context the term "trometamol" refers to
(tris(hydroxymethyl)aminomethane), also sometimes referred to as tris buffer.
In the present context, the term "phosphate buffer" refers to alkali metal and
alkaline
earth metal phosphate salts, such as Sodium orthophosphate, Potassium
orthoph osph ate, Calcium orthophosph ate, Sodium di phosphate, Potassium
diphosphate, Calcium diphosphate, Pentasodium triphosphate, Pentapotassium
triphosphate, Sodium polyphosphate, Potassium polyphosphate.
In an advantageous embodiment of the invention, the pH adjusting agent is
selected
from the group consisting of trometamol, amino acids and phosphate buffer, or
any
combination thereof
In an advantageous embodiment of the invention, the pH adjusting agent is
selected
from the group consisting of trometamol and phosphate buffer, or any
combination
thereof
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Trometamol and phosphate buffers have a desirable relative neutral taste,
hence the
use of these pH regulating agents may not compromise the taste and mouthfeel
of the
pouch composition.
In an advantageous embodiment of the invention, the pH adjusting agent is
selected
from the group consisting of trometamol.
In an embodiment of the invention, the pH adjusting agent is trometamol.
In an embodiment of the invention, the p1-1 adjusting agent comprises
trometamol
In an embodiment of the invention, the pH adjusting agent is amino acid.
In an embodiment of the invention, the pH adjusting agent comprises an amino
acid.
In an embodiment of the invention, the pH adjusting agent is phosphate buffer.
In an embodiment of the invention, the pH adjusting agent comprises phosphate
buffer.
In an embodiment of the invention, the pH adjusting agent is phosphate buffer
selected
from the group consisting of Sodium orthophosphate, Potassium orthophosphate,
Calcium orthophosphate, Sodium diphosphate, Potassium diphosphate, Calcium
diphosphate, Pentasodium triphosphate, Pentapotassium triphosphate, Sodium
polyphosphate, Potassium polyphosphate, and combinations thereof
In an embodiment, the pH regulating agent is an alkali metal phosphate buffer.
In an embodiment, the phosphate buffer is an alkali metal phosphate buffer.
In an embodiment, the phosphate buffer is an alkali metal phosphate buffer
selected
from the group consisting of Sodium orthophosphate, Potassium orthophosphate,
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Sodium diphosphate, Potassium diphosphate, Pentasodium triphosphate,
Pentapotassium triphosphate, Sodium polyphosphate, Potassium polyphosphate,
and
combinations thereof
In an embodiment, the phosphate buffer is provided as a water-soluble
composition.
In an embodiment of the invention, the pH adjusting agent does not comprise
carbonate
and/or bicarbonate.
In an embodiment of the invention, the pH adjusting agent is a non-carbonate
and/or
non-bicarbonate buffers, or combinations thereof
In an embodiment of the invention, the pouch composition is free of
carbonates.
In an embodiment of the invention, the pouch composition comprises humectant.
In an embodiment, the humectant is selected from the list of glycerol,
propylene glycol,
alginate, pectin, modified starch, hydroxypropyl cellulose, triacetin,
polyethylene
glycol (PEG), xanthan gum, and combinations thereof.
In an embodiment, the humectant is or comprises humectant in an amount of 0.5
to
10%, such as 0.5 to 5% by weight of the pouch composition, such as 1-3% by
weight
of the pouch composition.
In an embodiment, the humectant is or comprises alginate, such as sodium
alginate,
e.g. in an amount of 0.5 to 10%, such as 0.5 to 5% by weight of the pouch
composition,
such as 1-3% by weight of the pouch composition.
In an embodiment of the invention, the pouch composition is free of alginate.
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In an embodiment of the invention the pouch composition is free of humectants
consisting of alginate, pectin and xanthan gum.
In an embodiment of the invention the pouch composition is free of humectants
5 selected from the list of glycerol, propylene glycol,
alginate, pectin, modified starch,
hydroxypropyl cellulose, triacetin, polyethylene glycol (PEG), xanthan gum,
and
combinations thereof
In an embodiment of the invention the pouch composition is free of humectants.
In an advantageous embodiment of the invention, the pouch composition is
adapted to
release at least 30% nicotine within 10 minutes when exposed to in vitro
conditions
described in example 7A.
In an advantageous embodiment of the invention, the pouch composition is
adapted to
release at least 25% more nicotine within 5 minutes compared to a
corresponding
pouch composition without divalent cations when exposed to the in vitro
conditions
described in example 7A.
In an advantageous embodiment of the invention, the pouch composition
comprises
sodium chloride in an amount of 0.0-3.0% by weight of the pouch compositions,
such
as 0.05 ¨ 1.0 A by weight of the pouch composition, such as 0.1 ¨ 1.0% by
weight of
the pouch composition.
Sodium chloride may advantageously be added in small amounts, i.e. 0.0-3.0% by
weight as a flavor enhancer. Adding higher amounts of sodium chloride could
induce
an undesirable taste or mouthfeel.
In an advantageous embodiment of the invention, the pouch composition further
comprises a preservative.
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The preservative may help to preserve the pouch composition against
undesirable
microbiological growths.
In an advantageous embodiment of the invention, the pouch composition further
comprises a preservative in an amount of 0.05 to 0.5% by weight of the pouch
composition, such as 0.1 to 0.2% by weight of the pouch composition.
Non-limiting examples of usable preservatives within the scope of the
invention
includes sorbic acid (E200) and salts thereof (e.g. sodium sorbate (E201),
potassium
sorbate (E202), calcium sorbate (E203)), benzoic acid (E210) and salts thereof
(e.g.
sodium benzoate (E211), potassium benzoate (E212), calcium benzoate (E213)).
In an advantageous embodiment of the invention, the pouch composition
comprises
less than 0.1% by weight of preservatives, such as less than 0.05% by weight
of
preservatives.
Thus, the pouch composition may comprise preservatives in an amount of 0 to
0.1 %
by weight of preservatives, such as in an amount of 0 to 0.05% by weight of
preservatives. This includes zero content of preservatives, i.e. that the
pouch
composition is free of preservatives. The low amount or even absence of
preservative
may be realized by obtaining a relatively alkaline environment, particularly
by the use
of free-base nicotine.
In an advantageous embodiment of the invention, the pouch composition is free
of
preservatives.
In an advantageous embodiment of the invention, the pouch composition is a non-
tobacco pouch composition.
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In an advantageous embodiment of the invention, the pouch composition
comprises
less than 2.00/0 by weight of tobacco, such as less than 1.0% by weight of
tobacco, such
as less than 0.5% by weight of tobacco, such as 0.0% by weight of tobacco.
In an advantageous embodiment of the invention, the pouch composition
comprises a
non-tobacco fiber.
In an advantageous embodiment of the invention, the pouch composition is a
powdered
composition.
The invention further relates to an oral pouched nicotine product comprising a
saliva-
permeable pouch and the pouch composition of according to the invention or any
of
its embodiments enclosed in said pouch.
In an advantageous embodiment of the invention, the pouched nicotine product
comprises nicotine in an amount of 0.5 to 20 mg, such as 1.0 to 20 mg, such as
5.0 to
15 mg.
In an advantageous embodiment of the invention, the pouched nicotine product
comprises nicotine-ion exchange combination in an amount of 1 to 100 mg per
pouch.
In an embodiment of the invention, the pouched nicotine product comprises
nicotine-
ion exchange combination in an amount of 1 to 100 mg per pouch, such as 10 to
90
mg per pouch, such as 10 to 80 mg per pouch, such as 20 to 80 mg per pouch,
such as
30 to 80 mg per pouch, such as 40 to 80 mg per pouch, such as 50 to 80 mg per
pouch.
In an embodiment of the invention, the pouched nicotine product comprises
nicotine-
ion exchange combination in an amount of 1 to 100 mg per pouch, such as 10 to
80
mg per pouch, such as 10 to 60 mg per pouch, such as 20 to 60 mg per pouch,
such as
20 to 50 mg per pouch.
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In an embodiment of the invention, the divalent cations are provided as a salt
having a
water-solubility of 5 - 500 grams per 100 mL of water measured at 25 degrees
Celsius,
atmospheric pressure and pH 7.0, such as 5 - 350 grams per 100 mL of water
measured
at 25 degrees Celsius, atmospheric pressure and pH 7Ø
In an embodiment of the invention, the inorganic divalent cations are provided
as a
salt in an amount of between 0.1 and 15.0% by weight of the composition, such
as
between 0.1 and 10.0% by weight of the composition, such as between 0.5 and
10.0%
by weight of the composition, and the inorganic divalent cations are provided
as an
inorganic salt comprising inorganic anions selected from the group consisting
of
chloride, bromide, hydrogen carbonate, sulfate, and any combination thereof
In an embodiment of the invention, the inorganic divalent cations are provided
as a
salt in an amount of between 0.1 and 15.0% by weight of the composition, such
as
between 0.1 and 10.0% by weight of the composition, such as between 0.5 and
10.0%
by weight of the composition, and the divalent cations are provided as a water-
soluble
salt having a water-solubility of at least 5 gram per 100 mL of water measured
at 25
degrees Celsius, atmospheric pressure and pH 7Ø
In an embodiment of the invention, the inorganic divalent cations are provided
as an
inorganic salt in an amount of between 0.1 and 15.0% by weight of the
composition,
such as between 0.1 and 10.0% by weight of the composition, such as between
0.5 and
10.0% by weight of the composition, and the water-soluble salt has a water-
solubility
of at least 5 gram per 100 mL of water measured at 25 degrees Celsius,
atmospheric
pressure and pH 7Ø
In an embodiment of the invention, the inorganic divalent cations are provided
as a
salt in an amount of between 0.1 and 15.0% by weight of the composition, such
as
between 0.1 and 10.0% by weight of the composition, such as between 0.5 and
10.0%
by weight of the composition and the pouch composition comprises nicotine in
an
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amount of at least 0.1% by weight, such as least 0.2% by weight of the pouch
composition.
In an embodiment of the invention, the inorganic divalent cations are provided
as a
salt in an amount of between 0.1 and 15.0% by weight of the composition, such
as
between 0.1 and 10.0% by weight of the composition, such as between 0.5 and
10.0%
by weight of the composition, the pouch composition comprises nicotine in an
amount
of at least 0.1% by weight, such as least 0.2% by weight of the pouch
composition,
and the solid oral nicotine formulation comprises inorganic divalent cations
in a molar
ratio of at most 5 relative to the amount of nicotine in the nicotine-ion
exchange resin
combination, such as at most 3.75 relative to the amount of nicotine in the
nicotine-
ion exchange resin combination, such as at most 2.5 relative to the amount of
nicotine in the nicotine-ion exchange resin combination.
In an embodiment of the invention, the inorganic divalent cations are provided
as a
salt in an amount of between 0.1 and 150% by weight of the composition, such
as
between 0.1 and 10.0% by weight of the composition, such as between 0.5 and
10.0%
by weight of the composition, the pouch composition comprises nicotine in an
amount
of at least 0.1% by weight, such as least 0.2% by weight of the pouch
composition,
and the pouch composition comprises inorganic divalent cations in a molar
ratio of at
most 6.5 relative to the amount of nicotine in the nicotine-ion exchange resin
combination, such as at most 6.0 relative to the amount of nicotine in the
nicotine-ion
exchange resin combination, such as at most 5 relative to the amount of
nicotine in
the nicotine-ion exchange resin combination, such as at most 3.75 relative to
the
amount of nicotine in the nicotine-ion exchange resin combination, such as at
most
2.5 relative to the amount of nicotine in the nicotine-ion exchange resin
combination.
In an embodiment of the invention, the inorganic divalent cations are provided
as a
salt in an amount of between 0.1 and 15.0% by weight of the composition, such
as
between 0.1 and 10.0% by weight of the composition, such as between 0.5 and
10.0%
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by weight of the composition, and the pouch composition comprises nicotine-ion
exchange combination in an amount of 0.1 to 20% by weight of the pouch
composition.
In an embodiment of the invention, the inorganic divalent cations are provided
as a
5 salt in an amount of between 0.1 and 15.0% by weight of the
composition, such as
between 0.1 and 10.0% by weight of the composition, such as between 0.5 and
10.0%
by weight of the composition, and the pouch composition comprises nicotine-ion
exchange combination in an amount of 0.1 to 20% by weight of the pouch
composition,
and the solid oral nicotine formulation comprises inorganic divalent cations
in a molar
10 ratio of at most 5 relative to the amount of nicotine in the
nicotine-ion exchange resin
combination, such as at most 3.75 relative to the amount of nicotine in the
nicotine-
ion exchange resin combination, such as at most 2.5 relative to the amount of
nicotine in the nicotine-ion exchange resin combination.
15 In an embodiment of the invention, the inorganic divalent
cations are provided as a
salt in an amount of between 0.1 and 150% by weight of the composition, such
as
between 0.1 and 10.0% by weight of the composition, such as between 0.5 and
10.0%
by weight of the composition, and the pouch composition comprises nicotine-ion
exchange combination in an amount of 0.1 to 20% by weight of the pouch
composition,
20 and the pouch composition comprises inorganic divalent cations
in a molar ratio of at
most 6.5 relative to the amount of nicotine in the nicotine-ion exchange resin
combination, such as at most 6.0 relative to the amount of nicotine in the
nicotine-ion
exchange resin combination, such as at most 5 relative to the amount of
nicotine in
the nicotine-ion exchange resin combination, such as at most 3.75 relative to
the
25 amount of nicotine in the nicotine-ion exchange resin
combination, such as at most
2.5 relative to the amount of nicotine in the nicotine-ion exchange resin
combination.
In an embodiment of the invention, the nicotine-ion exchange resin combination
comprises nicotine in an amount of between 5 and 50% by weight and ion-
exchange
30 resin in an amount between 10 and 95% by weight, and the ion
exchange resin is
polacrilex resin.
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In an embodiment of the invention, the pouch composition comprises nicotine-
ion
exchange combination in an amount of 0.1 to 20% by weight of the pouch
composition,
and the nicotine-ion exchange resin combination comprises nicotine in an
amount of
between 5 and 50% by weight and ion-exchange resin in an amount between 10 and
95% by weight, and the ion exchange resin is polacrilex resin.
In an embodiment of the invention, the inorganic divalent cations are provided
as a
salt in an amount of between 0.1 and 15.0% by weight of the composition, such
as
between 0.1 and 10.0% by weight of the composition, such as between 0.5 and
10.0%
by weight of the composition, and the pouch composition comprises nicotine-ion
exchange combination in an amount of 0.1 to 20% by weight of the pouch
composition,
and the pouch composition comprises water in an amount of 15-65% by weight of
the
composition, such as 15-60% by weight of the composition, such as 15-500/o by
weight
of the composition, such as 20-50% by weight of the composition, such as 20-
40% by
weight of the composition
In an embodiment of the invention, the at least one sugar alcohol is selected
from
xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and
mixtures thereof,
and the pouch composition comprises sugar alcohol in an amount of 1 to 80% by
weight of the composition, such as 2 to 70% by weight of the composition, such
as 5
to 60% by weight of the composition, such as 10 to 50% by weight of the
composition,
such as 15 to 50% by weight of the composition.
In an embodiment of the invention, the inorganic divalent cations are provided
as a
salt in an amount of between 0.1 and 15.0% by weight of the composition, such
as
between 0.1 and 10.0% by weight of the composition, such as between 0.5 and
10.0%
by weight of the composition, and the pouch composition comprises nicotine-ion
exchange combination in an amount of 0.1 to 20% by weight of the pouch
composition,
and the pouch composition comprises water in an amount of 15-65% by weight of
the
composition, such as 15-60% by weight of the composition, such as 15-50% by
weight
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of the composition, such as 20-50% by weight of the composition, such as 20-
40% by
weight of the composition, and the pouch composition comprises sugar alcohol
in an
amount of 1 to 80% by weight of the composition, such as 2 to 70% by weight of
the
composition, such as 5 to 600/o by weight of the composition, such as 10 to
50% by
weight of the composition, such as 15 to 50% by weight of the composition.
In an embodiment of the invention, the pouch composition comprises sugar
alcohol in
an amount of 1 to 80% by weight of the composition, such as 2 to 70% by weight
of
the composition, such as 5 to 60% by weight of the composition, such as 10 to
500/0
by weight of the composition, such as 15 to 50% by weight of the composition,
and
the pouch composition comprises said water-insoluble fiber in an amount
between 5
and 50 % by weight of the pouch composition, such as 10-45% by weight of the
pouch
composition, such as 15-40% by weight of the pouch composition.
In an embodiment of the invention, the pouch composition comprises sugar
alcohol in
an amount of 1 to 80% by weight of the composition, such as 2 to 70% by weight
of
the composition, such as 5 to 60% by weight of the composition, such as 10 to
50%
by weight of the composition, such as 15 to 50% by weight of the composition,
and
the pouch composition comprises said water-insoluble fiber in an amount
between 5
and 50 % by weight of the pouch composition, such as 10-45% by weight of the
pouch
composition, such as 15-40% by weight of the pouch composition, and the pouch
composition comprises water in an amount of 15-65% by weight of the
composition,
such as 15-60% by weight of the composition, such as 15-50% by weight of the
composition, such as 20-50% by weight of the composition, such as 20-40% by
weight
of the composition.
In an embodiment of the invention, the pouch composition comprises said water-
insoluble fiber in an amount between 5 and 50 % by weight of the pouch
composition,
such as 10-45% by weight of the pouch composition, such as 15-40% by weight of
the
pouch composition, and the water-insoluble fiber is selected from wheat
fibers, pea
fibers, rice fiber, maize fibers, oat fibers, tomato fibers, barley fibers,
rye fibers, sugar
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beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers,
cocoa fibers,
cellulose fibers, bran fibers, bamboo fibers, powdered cellulose, and
combinations
thereof
In an embodiment of the invention, the inorganic divalent cations are provided
as a
salt in an amount of between 0.1 and 15.0% by weight of the composition, such
as
between 0.1 and 10.0% by weight of the composition, such as between 0.5 and
10.0%
by weight of the composition, and the pouch composition comprises nicotine-ion
exchange combination in an amount of 0.1 to 20% by weight of the pouch
composition,
and the pouch composition comprises water in an amount of 15-65% by weight of
the
composition, such as 15-60% by weight of the composition, such as 15-500/0 by
weight
of the composition, such as 20-50% by weight of the composition, such as 20-
40% by
weight of the composition, and the pouch composition comprises sugar alcohol
in an
amount of 1 to 80% by weight of the composition, such as 2 to 70% by weight of
the
composition, such as 5 to 60% by weight of the composition, such as 10 to 50%
by
weight of the composition, such as 15 to 50% by weight of the composition, and
the
pouch composition comprises said water-insoluble fiber in an amount between 5
and
50 % by weight of the pouch composition, such as 10-45% by weight of the pouch
composition, such as 15-40% by weight of the pouch composition.
In an embodiment of the invention, the pouch composition comprises pH
regulating
agent in an amount between 0.01 and 15% by weight of the pouch composition,
such
as between 0.5 and 10% by weight of the pouch composition, such as between 1
and
10% by weight of the pouch composition, such as between 5 and 10% by weight of
the pouch composition, and the pH regulating agent is selected from the group
consisting Sodium carbonate, Sodium bicarbonate, Potassium carbonate, and
Magnesium carbonate; Potassium bicarbonate; trometamol; phosphate buffer, or
any
combination thereof.
In an embodiment of the invention, the pouch composition comprises pH
regulating
agent in an amount between 0.01 and 15% by weight of the pouch composition,
such
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as between 0.5 and 10% by weight of the pouch composition, such as between 1
and
100/0 by weight of the pouch composition, such as between 5 and 10% by weight
of
the pouch composition, and the pH regulating agent is selected from the group
consisting Sodium carbonate, Sodium bicarbonate, Potassium carbonate, and
Magnesium carbonate; Potassium bicarbonate; trometamol; phosphate buffer, or
any
combination thereof, and the divalent cations are provided as a water-soluble
salt
haying a water-solubility of at least 5 gram per 100 mL of water measured at
25
degrees Celsius, atmospheric pressure and pH 7Ø
In an embodiment of the invention, the pouch composition comprises pH
regulating
agent in an amount between 0.01 and 15% by weight of the pouch composition,
such
as between 0.5 and 10% by weight of the pouch composition, such as between 1
and
10% by weight of the pouch composition, such as between 5 and 10% by weight of
the pouch composition, and the pH regulating agent is selected from the group
consisting Sodium carbonate, Sodium bicarbonate, Potassium carbonate, and
Magnesium carbonate; Potassium bicarbonate; trometamol; phosphate buffer, or
any
combination thereof, and the inorganic divalent cations are provided as an
inorganic
salt comprising inorganic anions selected from the group consisting of
chloride,
bromide, hydrogen carbonate, sulfate, and any combination thereof.
The invention further relates to a pouch composition comprising
a nicotine-ion exchange resin combination, and
inorganic multivalent cations.
In an advantageous embodiment of the invention, said multivalent cations are
selected
from the group consisting of multivalent ions of calcium, magnesium, zinc,
aluminum,
barium, iron, manganese, copper, lead, cobalt, nickel, such as Ca2+, Mg2+,
Zn2+,
A13+, Ba2+, Fe2+, Fe3+, Fe4+, Mn2+, Mn4+, Cu4+, or any combinations thereof.
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In an embodiment of the invention, the multivalent cations are selected from
the group
consisting of Ca2+, Mg2+, Zn2+, Ba2+, Fe2+, Fe3+, Fe4+, Al3+, Mn2+, Mn4+,
Cu4+, and any combination thereof
5 In an advantageous embodiment of the invention, the
multivalent cations are selected
from the group consisting of trivalent cations of aluminum, divalent cations
of calcium,
magnesium, iron, zinc, and any combination thereof
In an advantageous embodiment of the invention, the multivalent cations are
trivalent
10 cations.
In an embodiment the trivalent cation is aluminum.
In an embodiment of the invention, the multivalent cations comprise aluminum
15 chloride
In an embodiment of the invention, the multivalent cations are selected from
the group
consisting of aluminum chloride, divalent cations of calcium, magnesium, iron,
zinc,
and any combination thereof
In an advantageous embodiment of the invention, the multivalent cations are
selected
from the group consisting of divalent cations of calcium, magnesium, iron,
zinc, and
any combination thereof
In an advantageous embodiment of the invention, the multivalent cations are
selected
from the group consisting of divalent cations of calcium, magnesium, and any
combination thereof
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DETAILED DESCRIPTION
As used herein the term "pouch composition" refers to the composition for use
in an
oral pouch, i.e. in pouches for oral use. Thus, pouch composition refers to
the
composition enclosed within the pouch. Also, the terms "pouch composition-,
"nicotine pouch composition" and "solid oral nicotine formulation" are used
interchangeably, when referring to the composition being enclosed within the
pouch.
As used herein the term -nicotine" refers to nicotine used as a
refined/isolated
substance. Particularly, nicotine does not refer to tobacco materials having a
content
of nicotine. Thus, when referring to nicotine amounts also to be understood as
the
nicotine dose, the amounts refers to the amount of pure nicotine.
Nicotine also covers nicotine not obtained from tobacco, often referred to as
synthetic
nicotine.
As used herein, a "molar ratio" refers to the ratio of the molar content of
the first
component divided by the molar content of the second component.
The relative content between the first component and the second component may
also
be presented as equivalents of the first component relative to the second
component.
Thus, a pouch comprising divalent cations in a molar ratio of 0.1 relative to
the amount
of nicotine in the nicotine-ion exchange resin combination, may also be
presented as a
pouch comprising 0.1 eq. of divalent cations relative to the amount of
nicotine in the
nicotine-ion exchange resin combination, i.e. a pouch comprising 0.1 eq. of
divalent
cations and 1 eq. of nicotine in the nicotine-ion exchange resin combination.
As used herein the term "free-base nicotine" refers to non-protonated form of
nicotine,
and therefore does not include nicotine salts or nicotine provided as a
complex between
nicotine and an ion exchange resin. Nevertheless, the free-base nicotine may
be mixed
with an amount of ion exchange resin or water-soluble compositions such as
sugar
alcohols or water-soluble fibers. While free-base nicotine includes both free-
base
nicotine extracted from tobacco as well as synthetically manufactured free-
base
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nicotine, the free-base nicotine is not provided in the form of tobacco or
powdered
tobacco. Typically, free-base nicotine is provided as a liquid.
As used herein the term "pouch" is intended to mean a container typically
formed by
a web of a fibrous material enclosing a cavity. The pouch is pouch designed
for
administration of an active ingredient in the oral cavity, and thus it is
adapted for oral
use, it is non-toxic and not water-soluble. The fibrous material may e.g. form
a woven
or non-woven web or fabric. The pouch may for example be sealed by bonding two
corresponding pieces of web or fabric to each other along their edges to form
a cavity
for the nicotine and the non-water-soluble composition. In order to release
the nicotine,
the pouch is made water-permeable so as to allow saliva from the oral cavity
to
penetrate the pouch and enter the cavity, where the saliva can come into
contact with
the nicotine, whereby the nicotine are released from the oral pouch.
As used herein, the term "nicotine-ion exchange resin combination" refer
to a combination comprising nicotine complexed with ion exchange resin and/or
free-
base nicotine mixed with ion exchange resin.
As used herein, the term "nicotine complexed with ion-exchange resin" refers
to
nicotine bound to an ion exchange resin.
In the present context, the term "free-base nicotine mixed with ion exchange
resin"
refers to a mixture comprising free-base nicotine and ion exchange resin. It
is noted
that even if some embodiments comprise a combination of nicotine complexed
with
ion exchange resin and nicotine in its free-base form mixed with ion exchange
resin,
the term "free-base nicotine mixed with ion exchange resin" requires the
presence of
nicotine in its free-base form. In some embodiments, the mixture is an aqueous
mixture. Free-base nicotine and water is mixed with ion-exchange resin,
whereby a
mixture comprising both free-base nicotine and ion exchange resin is obtained.
Free-
base nicotine mixed with ion exchange resin is referred to as "premix" in the
examples.
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As used herein the term "powder composition" refers to composition in the form
of
powder, i.e. as a particulate material having a relatively small particle
size, for example
between 1 and 1200 micrometer. Particularly, by powder composition is not
meant a
powdered tobacco.
As used herein the term "humectant" is understood as a moistening agent used
to keep
pouches moist, i.e. a humectant is added to the pouch composition with the
purpose of
keeping the pouch moist. Hence, the term humectant does not refer to
substances added
for other purposes, hereunder also hygroscopic substances added for other
purposes,
such as sugar alcohols, water-insoluble fibers and glycerol associated with
ion-
exchange resin in nicotine-ion exchange resin combinations, such as nicotine
polacrilex. Examples of humectants include alginate, propylene glycol,
hydroxypropyl
cellulose, and glycerol. It is noted that when glycerol is included as a
humectant, the
glycerol is added as free glycerol and therefore liquid at room temperature.
Further
examples of humectants include triacetin, modified starch, pectin, xanthan
gum, etc.
The term humectant does not refer to sugar alcohols comprising 4 or more
carbons.
Also, the term humectant does not refer to fibers, such as water-insoluble
fiber, such
as wheat fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato
fibers, barley
fibers, rye fibers, sugar beet fibers, buckwheat fibers, potato fibers,
cellulose fibers,
apple fibers, cocoa fibers, cellulose fibers, bran fibers, bamboo fibers,
powdered
cellulose, and combinations thereof. Also, the term humectant does not include
e.g.
NaCl.
As used herein the term "water-soluble" refers to a relatively high water-
solubility, for
example a water-solubility of more than 5 gram of water-soluble composition or
substance per 100 mL of water measured at 25 degrees Celsius, atmospheric
pressure
and pH of 7Ø When referring to a "soluble" composition or substance, water-
soluble
is meant, unless otherwise stated.
As used herein the term "water-insoluble" refers to relatively low water-
solubility, for
example a water-solubility of less than 0.1 gram of composition or substance
per 100
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mL of water measured at 25 degrees Celsius, atmospheric pressure and pH of
7Ø
When referring to "insoluble", water-insoluble is meant unless otherwise
stated.
Therefore, compositions or substances having a water-solubility of between 0.1
and 5
gram per of composition or substance per 100 mL of water measured at 25
degrees
Celsius, atmospheric pressure and pH of 7.0 are considered neither water-
soluble nor
water-insoluble, but having an intermediate water-solubility.
The pouches of the invention provide a nicotine release into the oral cavity.
A release
profile of nicotine may be obtained which both comprises a fast release period
and a
sustained release period.
As used herein the term "fast release" or "fast release period" may refer to
the initial
2 minutes of the nicotine release profile, whereas the term "sustained release
period
refers" to the subsequent period of the release profile until end of
experiment or end
of use.
As used herein the term "fast release rate" refers to the released nicotine
per minute
within the initial 2 minutes.
As used herein the term -effective release" refers to the total release of
nicotine
over the release period of the experiment or the use period.
As used herein, the term "dissolve" is the process where a solid substance
enters
a solvent (such as oral saliva or water within the pouch) to yield a solution.
Typically, the pouches comprise openings, where the characteristic opening
dimension
is adapted to a characteristic dimension of the matrix composition so as to
retain the
matrix composition inside the pouch before use and/or to retain a part of the
matrix
composition, such as an water-insoluble composition, inside the pouch during
use.
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In order to obtain a pouch having suitable opening dimensions in view of the
matrix
composition to be used, the material for the pouch may be selected
accordingly, e.g.
comprising e.g. woven and/or non-woven fabric.
5 In other words, according to the various embodiments, the
pouch forms a membrane
allowing passage of saliva and prevents or inhibits passage of said matrix
composition.
The membrane of the pouch may be of any suitable material e.g. woven or non-
woven
fabric (e.g. cotton, fleece etc.), heat sealable non-woven cellulose or other
polymeric
materials such as a synthetic, semi-synthetic or natural polymeric material.
An
10 example of suitable pouch material is paper made of pulp and a
small amount of wet
strength agent. A material suitable for use must provide a semi-permeable
membrane
layer to prevent the powder or composition from leaving the bag or pouch
during use.
Suitable materials are also those that do not have a significant impact on the
release of
nicotine from the pouch.
The pouch composition is filled into pouches and is maintained in the pouch by
a
sealing. An ideal pouch is chemically and physically stable, it is
pharmaceutically
acceptable, it is insoluble in water, it is easy to fill with powder and seal,
and it provides
a semi-permeable membrane layer which prevent the powder from leaving the bag,
but permit saliva and therein dissolved or sufficiently small suspended
components
from the pouch composition in the pouch, such as nicotine, to pass through
said pouch.
The pouch may be placed in the oral cavity by the user. Saliva then enters
into the
pouch, and the nicotine and other components, which are soluble in saliva,
start to
dissolve and are transported with the saliva out of the pouch into the oral
cavity, where
the nicotine may be absorbed.
According to an embodiment of the invention, the pouch composition may further
comprise one or more additives.
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In an embodiment of the invention, said additives are selected from the group
consisting of bile salts, cetomacrogols, chelating agents, citrates,
cyclodextrins,
detergents, enamine derivatives, fatty acids, labrasol, lecithins,
phospholipids, syntetic
and natural surfactants, nonionic surfactants, cell envelope disordering
compounds,
solvents, steroidal detergents, chelators, solubilization agents, charge
modifying
agents, pH regulating agents, degradative enzyme inhibitors, mucolytic or
mucus
clearing agents, membrane penetration-enhancing agents, modulatory agents of
epithelial junction physiology, vasodilator agents, selective transport-
enhancing
agents, or any combination thereof pH regulating agents include buffers.
In an embodiment of the invention, said additives are selected from the group
consisting of cetylpyridinium chloride (CPC), benzalkonium chloride, sodium
lauryl
sulfate, polysorbate 80, Polysorbate 20, cetyltrimethylammonium bromide,
laureth 9,
sodium salicylate, sodium EDTA, EDTA, aprotinin, sodium taurocholate,
saponins,
bile salt derivatives, fatty acids, sucrose esters, azone emulsion, dextran
sulphate,
linoleic acid, labrafil, transcutol, urea, azone, nonionic surfactants,
sulfoxides, sauric
acid/PG, POE 23 lauryl ether, methoxysalicylate, dextran sulfate, methanol,
ethanol,
sodium cholate, Sodium taurocholate, Lysophosphatidyl choline,
Alkylglycosides,
polysorbates, Sorbitan esters, Poloxamer block copolymers, PEG-35 castor oil,
PEG-
hydrogenated castor oil, Caprocaproyl macrogo1-8 glycerides, PEG-8
caprylic/capric,
glycerides, Dioctyl sulfosuccinate, Polyethylene lauryl ether, Ethoxydiglycol,
Propylene glycol, mono-di-caprylate, Glycerol monocaprylate, Glyceryl fatty
acids
(C8-C18) ethoxylated Oleic acid, Linoleic acid, Glyceryl
caprylate/caprate,
Glyceryl monooleate, Glyceryl monolaurate, Capryliccapric triglycerides,
Ethoxylated nonylphenols, PEG-(8-50) stearates, Olive oil PEG-6, esters,
Triolein
PEG-6 esters, Lecithin, d-alpha tocopherol polyethylene glycol 1,000
succinate, Citric
acid, Sodium citrate, BRIJ, Sodium laurate, 5-methoxysalicylic acid, Bile
salts, Acetyl
salicylate, ZOT, Docosahexaenoic acid, Alkylglycosides, Sodium glycocholate
(GC-
Na), Sodium taurocholate (TC-Na), EDTA, Choline salicylate, Sodium caprate
(Cap-
Na), N-lauryl-beta-D-maltopyranoside (LM), Diethyl maleate, Labrasol, Sodium
salicylate, Mentol, Alkali metal alkyl sulphate, Sodium lauryl sulphate,
Glycerin, Bile
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acid, Lecithin, phosphatidylcholine,
phosphatidylserine, sphingomy elin,
phophatidylethanolamine, cephalin, lysolecithin, Hyaluronic acid: alkalimetal
salts,
sodium, alkaline earth and aluminum, Octylphenoxypolyethoxyethanol, Glycolic
acid,
Lactic acid, Chamomile extract, Cucumber extract, Borage oil, Evening primrose
oil,
Polyglycerin, Lysine, Polylysine, Triolein, Monoolein, Monooleates,
Monolaurates,
Polydocanol alkyl ethers, Chenodeoxycholate, Deoxycholate, Glycocholic acid,
Taurocholic acid, Glycodeoxycholic acid, Taurodeoxycholic acid, Sodium
glycocholate, Phosphatidylcholine, Phosphatidylserine,
Sphi ngomy el in,
Phosphatidylethanolamine, Cephalin, Lysolecithin, Alkali metal hyaluronates,
Chitosan, Poly-L-arginine, Alkyl glucoside, Saccharide alkyl ester, Fusidic
acid
derivatives, Sodium taurdihydrofusidate (STDHF), L-a-phosphatidylcholine
Didecanoyl (DDPC), Nitroglycerine, nitropruside, N005 [3-(2-hydroxy-1-(methyl-
ethyl)-2-nitrosohydrazino)-1- propanamine], NOC12 [iV-ethy1-2-(1-ethyl-hydroxy-
2-
nitrosohydrazino)-ethanamine, SNAP [S-nitroso-N-acetyl-DL-penicillamine, NORI,
NOR4, deacylmethyl sulfoxide, azone, salicylamide, glycery1-1,3-
diacetoacetate, 1,2-
isopropylideneglycerine-3-acetoacetate), Amino acids, Amino acid salts,
monoaminocarboxlic acids, Glycine, alanine, phenylalanine, proline,
hydroxyproline,
hydroxyamino acids, serine, acidic amino acids, aspartic acid, Glutamic acid,
Basic
amino acids, Lysine, N-acetylamino acids, N-acetylalanine, N-
acetylphenylalanine,
TM-acetylserine, N-acetylglycine, N-acetyllysine, N-acetylglutamic acid, N-
acetylproline, N-acetylhydroxyproline , lactic acid, malic acid and citric
acid and alkali
metal salts thereof, pyrrolidonecarboxylic acids, alkylpyrrolidonecarboxylic
acid
esters, N-alkylpyrrolidones, proline acyl esters, sodium lauryl phosphate,
sodium
lauryl sulphate, sodium oleyl phosphate, sodium myristyl sulphate,
polyoxyethylene
alkyl ethers, polyoxyethylene alkyl esters, and caproic acid, alkylsaccharide,
fusidic
acid, polyethylene glycol, cetyl alcohol, polyvinylpyrolidone, Polyvinyl
alcohol,
Lanolin alcohol, Sorbitan monooleate, Ethylene glycol tetraacetic acid, Bile
acid
conjugate with taurine, Cholanic acid and salts, Cyclodextran, Cyclodextrin,
Cy clodextrin (beta), Hy droxypropy1-13-cy clodetran, Sulfobutylether-I3-cy
clod extran,
Methyl-13-cyclodextrin, Chitosan glutamate, Chitosan acetate, Chitosan
hydrochloride,
Chitosan hydrolactate, 1-0-alkyl-2-hydroxy- sn-gly c ero-3 -phosphocholine, 3 -
0-alkyl-
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2-acetoyl-sn-glycero-1-phosphocholine, 1-0-alkyl-2-0-acetyl- sn-glycero-3-
phospho(N,N,N-trimethyl)hexanolamine, Propylene glycol, Tetradecylmaltoside
(TDM), Sucrose dedecanoate.
As used herein, the term "pH regulating agent- refers to agents, which active
adjust and regulates the pH value of the solution to which they have been
added or are
to be added. Thus, pH regulating agents may be acids and bases, including
acidic
buffering agents and alkaline buffering agents. On the other hand, pH
regulating agents
does not including substances and compositions that can only affect the pH by
dilution. Furthermore, p1-1 regulating agents does not include e.g. flavoring,
fillers,
etc.
In an embodiment of the invention, said pH-regulating agents are selected from
the
group consisting of Acetic acid, Adipic acid, Citric acid, Fumaric acid,
Glucono-6-
lactone, Gluconic acid, Lactic acid, Malic acid, Maleic acid, Tartaric acid,
Succinic
acid, Propionic acid, Ascorbic acid, Phosphoric acid, Sodium orthophosphate,
Potassium orthophosphate, Calcium orthophosphate, Sodium diphosphate,
Potassium
diphosphate, Calcium diphosphate, Pentasodium triphosphate, Pentapotassium
triphosphate, Sodium polyphosphate, Potassium polyphosphate, Carbonic acid,
Sodium carbonate, Sodium bicarbonate, Potasium carbonate, Calcium carbonate,
Magnesium carbonate, Magnesium oxide, trometamol, phosphate buffers, amino
acids, or any combination thereof.
According to various embodiments of the invention, one or more sugar alcohols
may
be included in the pouch as part of the pouch composition, e.g. as a carrier
or part
thereof, or as a sweetener. Suitable sugar alcohols include sugar alcohols
selected from
the group of sorbitol, erythritol, xylitol, lactitol, maltitol, mannitol,
hydrogenated
starch hydrolyzates, isomalt, or any combination thereof
In an embodiment of the invention the pouch composition comprises high
intensity
sweetener.
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Preferred high intensity sweeteners include, but are not limited to sucralose,
aspartame, salts of acesulfame, such as acesulfame potassium, alitame,
saccharin and
its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcones,
thaumatin,
monellin, stevioside and the like, alone or in combination.
In an embodiment of the invention, the pouch composition comprises bulk
sweeteners including sugar and/or sugarless components.
In an embodiment of the invention, the pouch composition comprises bulk
sweetener
in the amount of 1.0 to about 80% by weight of the pouch composition, more
typically constitute 5 to about 70% by weight of the pouch composition, and
more
commonly 10 to 60% by weight of the pouch composition or 10-50% by weight of
the pouch composition. Bulk sweeteners may function both as a sweetener and
also
as a humectant. In some embodiments, inclusion of certain ingredients may
limit the
about amounts of bulk sweetener further.
The sweeteners may often support the flavor profile of the pouch composition.
Sugar sweeteners generally include, but are not limited to saccharide-
containing
components commonly known in the art of pouches, such as sucrose, dextrose,
maltose, saccharose, lactose, sorbose, dextrin, trehalose, D-tagatose, dried
invert
sugar, fructose, levulose, galactose, corn syrup solids, glucose syrup,
hydrogenated
glucose syrup, and the like, alone or in combination.
The sweetener can be used in combination with sugarless sweeteners. Generally,
sugarless sweeteners include components with sweetening characteristics but
which
are devoid of the commonly known sugars and comprise, but are not limited to,
sugar
alcohols, such as sorbitol, mannitol, xylitol, hydrogenated starch
hydrolyzates,
maltitol, isomalt, erythritol, lactitol and the like, alone or in combination.
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As used herein the term "flavor" is understood as having its ordinary meaning
within
the art. Flavor includes liquid and powdered flavors. Thus, flavors do of
course not
include sweeteners (such as sugar, sugar alcohols and high intensity
sweeteners), or
acids providing pure acidity/sourness, nor compounds providing pure saltiness
(e.g.
5 NaCl) or pure bitterness. Flavor enhancers include substances
that only provide
saltiness, bitterness or sourness. Flavor enhancers thus include e.g. NaCl,
Citric acid,
ammonium chloride etc.
The flavors can be natural or synthetic flavors.
10 In an embodiment of the invention the pouch composition
comprises flavor. Flavor
may typically be present in amounts between 0.01 and 15% by weight of the
total
composition of the pouch, such as between 0.01 and 5% by weight of the total
composition.
15 Non-exhaustive examples of flavors suitable in embodiments of
the present invention
are coconut, coffee, chocolate, vanilla, grape fruit, orange, lime, menthol,
liquorice,
caramel aroma, honey aroma, peanut, walnut, cashew, hazelnut, almonds,
pineapple,
strawberry, raspberry, tropical fruits, cherries, cinnamon, peppermint,
wintergreen,
spearmint, eucalyptus, and mint, fruit essence such as from apple, pear,
peach,
20 strawberry, apricot, raspberry, cherry, pineapple, and plum
essence. The essential oils
include peppermint, spearmint, menthol, eucalyptus, clove oil, bay oil, anise,
thyme,
cedar leaf oil, nutmeg, and oils of the fruits mentioned above.
In various embodiments of the invention, the pouch composition comprises
25 composition modifier. The composition modifier may be added to
engineer the
properties of the pouch composition and/or parts thereof, such as flowability,
texture, homogeneity etc.
The composition modifiers may, according to various embodiments, be selected
30 group consisting of metallic stearates, modified calcium
carbonate, hydrogenated
vegetable oils, partially hydrogenated vegetable oils, polyethylene glycols,
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polyoxy ethylene monostearates, animal fats, silicates, silicates dioxide,
talc,
magnesium stearates, calcium stearates, fumed silica, powdered hydrogenated
cottonseed oils, hydrogenated vegetable oils, hydrogenated soya oil,
emulsifiers,
triglycerides, and mixtures thereof Particularly, metallic stearates, such as
magnesium stearate, may be advantageous.
The composition modifiers may be added to the pouch composition in various
ways.
For example, the composition modifiers may be added by full powder mixture
during
the last few minutes of the final mixing.
Alternatively, the composition modifiers may be added after granulation steps
on a
granulation premix.
The composition modifier, such as magnesium stearate, may have a sealing
effect
and can be used to control the release of the nicotine and the solubility of
the pouch.
According to an embodiment of the invention, the pouch composition comprises
polyvinylpyrrolidone (PVP). The pouch composition may also be free of PVP.
One advantage of the above embodiment may be that a more uniform composition
may be obtained.
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EXAMPLES
Example 1A ¨ Preparation of pouches designed for administration of nicotine
The material of the pouches is heat sealable non-woven cellulose, such as long
fiber
paper. Pouches that are not in form of non-woven cellulose fabric may also be
used
according to the invention.
The powder is filled into pouches and is maintained in the pouch by a sealing.
Example 1B ¨ Preparation of pouches designed for administration of nicotine
The material of the pouches is manufactured using rayon fibers, such as
viscose
rayon staple fibers. The pouch membrane is heat sealed along its edges except
for an
opening in one end into an inner cavity formed by the pouch membrane.
The powder is filled into pouches and is maintained in the pouch by a sealing.
Example 2: Preparation of nicotine premixes
A 60 liter planetary Bear Varimixer mixer was charged with water, and nicotine
was
weighed and added. The mixer was stirred at low speed for 1 minute at ambient
temperature. Then ion exchange resin Amberlite IRP64 was weighed and added to
the mixer. The mixer was closed, stirred at high speed for 5 minutes, opened
and
scraped down, if necessary. Finally the mixer was stirred for further 5
minutes at high
speed. The total process time was 20 minutes.
Thereby, mixtures of nicotine and cation exchange resin were produced from the
constituents stated in the below tables.
Premix I:
Constituent Amount (kg) Amount (%)
Nicotine 1.0 5.7
Water 12.5 71.4
Resin 4.0 22.9
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Total 17.5
100.0
Table 1. Ingredients used to manufacture nicotine premix I (5.7% nicotine). %
water
in obtained nicotine-resin composition: 71.4
Premix II:
Constituent Amount (kg)
Amount (%)
Nicotine 1.08 13.2
Water 2.80 34.1
Resin 4.32 52.7
Total 8.20
100.0
Table 2. Ingredients used to manufacture nicotine premix II (13.2% nicotine).
9/0 water in obtained nicotine-resin composition: 34.1.
Premix III:
Constituent Amount (kg)
Amount (%)
Nicotine 1.08 18.5
Water 0.44 7.5
Resin 4.32 74.0
Total 5.84
100.0
Table 3. Ingredients used to manufacture nicotine premix III (18.5% nicotine).
% water
in obtained nicotine-resin composition:7.5.
Premix IV:
Constituent Amount (kg)
Amount (%)
Nicotine 1.08 10.0
Water 5.40 50.0
Resin 4.32 40.0
Total 10.8
100.0
Table 4. Ingredients used to manufacture nicotine premix IV (10% nicotine). %
water
in obtained nicotine-resin composition: 50Ø
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Premix V:
Constituent Amount (kg) Amount (%)
Nicotine 1.78 20.0
Water 2.80 31.5
Resin 4.32 48.5
Total 8.90 100.0
Table 5. Ingredients used to manufacture nicotine premix V (20% nicotine). %
water
in obtained nicotine-resin composition: 31.5.
Premix VI:
Constituent Amount (kg) Amount (%)
Nicotine 3.05 30.0
Water 2.80 27.5
Resin 4.32 42.5
Total 10.17 100.0
Table 6. Ingredients used to manufacture nicotine premix VI (30% nicotine). %
water
in obtained nicotine-resin composition: 27.5.
Premix VII
Constituent Amount (kg) Amount (%)
Nicotine 3.83 35.0
Water 2.80 25.6
Resin 4.32 39.4
Total 10.95 100.0
Table 7. Ingredients used to manufacture nicotine premix VII (35% nicotine).
_______ 0/0 water
in obtained nicotine-resin composition: 25.6.
Premix VIII:
Constituent Amount (kg) Amount (%)
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Nicotine 5.15 42.0
Water 2.80 22.8
Resin 4.32 35.2
Total 12.27 100.0
Table 8. Ingredients used to manufacture nicotine premix VIII (42% nicotine)..
%
water in obtained nicotine-resin composition: 22.8.
Example 3: Preparation of pouch compositions
5 Pouches are prepared comprising powdered compositions as
outlined in table 9 ¨ 21.
The pouches are made as follows.
Fibers and water are mixed using a planetary Bear Varimixer mixer for 5
minutes.
Then, the following ingredients were added subsequently under continuous
mixing:
10 first the nicotine-ion exchange combination (NPR or premix)
(mixed for 2 minutes),
then the remaining ingredients except liquid flavor and glidant if any (mixed
for 2
minutes), then liquid flavor if any (mixed for 1 minute), then glidant if any
(mixed for
1 minute). The total mixing time is 9-11 minutes.
15 Example 4: Preparation of filled pouches
The final pouch composition is filled into pouches (target fill weight 500 mg
powder
per pouch). The pouch material of example 1A or 1B may be used. The powder is
filled into pouches and is maintained in the pouch by a sealing.
20 Example 5A: Pouches
The pouch compositions are prepared from the ingredients in table 9 using
preparation
method described in example 3.
The pouch compositions are filled into pouches as described in example 4
(pouch
material of examples lA was used, but 1B could also have been applied).
Pouches POI P02 P03 PO4 P05 P06 P07 P08 Cl
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Amount of 9.6 9.6 9.6 9.6 9.6 9.6
9.6 9.6
9.6 mg
nicotine mg mg mg mg mg mg mg mg
Water
content 25 25 25 25 25 25 25 25
25
twtcY01
Inorganic
divalent
0.5 0.75 1 1.5 2 3 4 7.5 -
cations
[eq]*
Raw
Content in weight percent
material
NPR (16%) 12.1 12.1 12.1 12.1 12.1 12.1
12.1 12.1 12.1
CaC12** 0.7 1.0 1.3 2.0 2.6 3.9
5.2 10.0 -
Xylitol 18.2 17.9 17.6 16.9 16.3 15.0 13.7 8.9 18.9
Purified
25 25 25 25 25 25 25 25 25
water
Wheat fiber 25 25 25 25 25 25 25 25
25
Sodium
2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
alginate
Sodium
5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0
carbonate
Flavor 8.9 8.9 8.9 8.9 8.9 8.9
8.9 8.9 8.9
High
intensity 1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0
sweetener
Potassium
0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1
sorb ate
Silicon
2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
dioxide
Total 100 100 100 100 100 100 100 100 100
Table 9: Pouch compositions.
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*The inorganic divalent cations is presented as equivalents relative to
nicotine in
nicotine ion-exchange combination.
**Divalent cations may be provided as a hydrated salt, such as dihydrate,
tetrahydrate,
hexahydrate etc. The weight% in the table are based on the non-hydrated salt.
Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.
Wheat fiber, trade name "Vitacel 600 WF plus". Other fibers may be used as
well,
such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice
fiber, maize
fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet
fibers, buckwheat
fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered
cellulose,
bran fibers, bamboo fibers, and cellulose fiber.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as
humectants. Other humectants as described herein may also be used in
combination
with sodium alginate, glycerol or HPC or as an alternative.
Sodium carbonate is used as an alkaline buffering agent. Other buffering
agents as
described herein may also be used in combination with sodium carbonate or an
alternative.
Flavor example, a mixture of e.g. menthol and peppermint may be used. Of
course,
other flavors as described herein may be use as well, in combination with
menthol
and/or peppermint or replacing these. The flavor may be liquid or flavored or
a
combination, i.e. a liquid flavor and a powdered flavor is added.
Acesulfame potassium and/or sucralose may as an example be used as high
intensity
sweeteners. Other usable high intensity sweeteners described herein may be
used in
combination with or instead of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described
herein
may also be used in combination with or instead of potassium sorbate.
Silicon dioxide is used as a glidant. Other possible glidants include e.g.
magnesium
stearate, starch and talc.
Example 5B:
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The pouch compositions are prepared from the ingredients in table 10 using
preparation method described in example 3.
The pouch compositions are filled into pouches as described in example 4
(pouch
material of examples lA was used, but 1B could also have been applied).
P1
Pouches P12 P13 P14 P15 P16 P17 P18 C2 C3
1
Amount of 9.6 9.6 9.6 9.6 9.6 9.6 9.6
9.6 9.6 9.6
nicotine mg mg mg mg mg mg mg mg mg mg
Water
content 15 25 30 35 30 30 30 10 25 25
[Art%]
Inorganic
divalent 1.0 1.0 1.0 1.0 1.0 1.5 2.0
1.0 -
cations [eq]*
Raw material Content in weight percent
12.
NPR (16`)/0) 1 12.1 12.1 12.1 12.1 12.1
12.1 12.1 12.1 12.1
CaCl2** 1.3 1.3 1.3 1.3 - - 1.3
-
MgCl2** - 1.1 1.7 2.2 -
37.
Xylitol 6 17.6 7.6 2.6 12.8 12.2 11.7 32.6 12.0 18.2
Purified
25 30 35 30 30 30 10 25 25
water
Wheat fiber 15 25 30 30 25 25 25 25
25 25
Sodium
2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
alginate
Sodium
5.0 5.0 5.0 5.0 5.0 5.0 5.0
5.0 5.0 5.0
carbonate
Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9
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6.9
0.7
NaCl
***
***
High
intensity 1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0 1.0
sweetener
Potassium
0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1
sorb ate
Silicon
2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
dioxide
Total
100 100 100 100 100 100 100 100 100 100
Table 10: Pouch compositions.
*The inorganic divalent cations are presented as equivalents relative to
nicotine in
nicotine ion-exchange combination.
**Divalent cations may be provided as a hydrated salt, such as dihydrate,
tetrahydrate,
hexahydrate etc. The weight% in the table are based on the non-hydrated salt.
***Corresponds to 1 eq of NaC1 relative to nicotine in nicotine ion-exchange
combination.
****Corresponds to 10 eq of NaCl relative to nicotine in nicotine ion-exchange
combination.
Pouch content: 500 mg total, i.e. nicotine cone 19.2 mg/g.
Wheat fiber, trade name "Vitacel 600 WF plus". Other fibers may be used as
well,
such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice
fiber, maize
fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet
fibers, buckwheat
fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered
cellulose,
bran fibers, bamboo fibers, and cellulose fiber.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as
humectants. Other humectants as described herein may also be used in
combination
with sodium alginate, glycerol or HPC or as an alternative.
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Sodium carbonate is used as an alkaline buffering agent. Other buffering
agents as
described herein may also be used in combination with sodium carbonate or an
alternative.
Flavor example, a mixture of e.g. menthol and peppermint may be used. Of
course,
5 other flavors as described herein may be use as well, in
combination with menthol
and/or peppermint or replacing these. The flavor may be liquid or flavored or
a
combination, i.e. a liquid flavor and a powdered flavor is added.
Acesulfame potassium and/or sucralose may as an example be used as high
intensity
sweeteners. Other usable high intensity sweeteners described herein may be
used in
10 combination with or instead of acesul fame potassium and/or
sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described
herein
may also be used in combination with or instead of potassium sorbate.
Silicon dioxide is used as a glidant. Other possible glidants include e.g.
magnesium
stearate, starch and talc.
Example SC:
The pouch compositions are prepared from the ingredients in table 11 using
preparation method described in example 3.
The pouch compositions are filled into pouches as described in example 4
(pouch
material of examples lA was used, but 1B could also have been applied).
Pouches
P20 P21 P22 P23 P24 P25 P26 P27 P28 P29
9.6 9.6 9.6 9.6 9.6 9.6 9.6 4.8 7.2 12.0
Amount of nicotine
mg mg mg mg mg mg mg mg mg mg
Water content
78 78 78 78 78 28 28 28 28 28
[wt%]
Inorganic cations
1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0 1.0
[eq]*
Raw material Content in weight percent
NPR (16%) 12.1 12.1 12.1 12.1 12.1 12.1 12.1
6.1 9.0 15.1
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CaCl2** - - -
- 0.7 1.0 1.6
Calcium acetate** 1.9 - -
Magnesium
- 1.7 -
acetate**
Calcium lactate** - - 2.6 - - -
- -
Magnesium
- 2.4 -
lactate**
FeCl2** - - 1.5 -
ZnC12** - 1.6 - -
A1C13** - - - - - 1.6 -
- -
Xylitol 11.0 11.2 10.3 10.5 11.4 11.3 11.3 18.2
15.0 8.3
Purified water 28 28 28 28 28 28 28
28 28 28
Wheat fiber 28 28 28 28 28 28 28
28 28 28
Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0
2.0 2.0 2.0 2.0
Sodium carbonate 5.0 5.0 5.0 5.0 5.0 5.0
5.0 5.0 5.0 5.0
Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9
High intensity
1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0 1.0
sweetener
Potassium sorbate 0.1 0.1 0.1 0.1 0.1 0.1
0.1 0.1 0.1 0.1
Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0
2.0 2.0 2.0 2.0
Total 100 100 100 100 100 100 100 100 100 100
Table 11: Pouch compositions.
*The inorganic cations are presented as equivalents relative to nicotine in
nicotine ion-
exchange combination.
**Multivalent cations may be provided as a hydrated salt, such as dihydrate,
tetrahydrate, hexahydrate etc. The weight% in the table are based on the non-
hydrated
salt.
Pouch content: 500 mg total.
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Wheat fiber, trade name "Vitacel 600 WF plus". Other fibers may be used as
well,
such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice
fiber, maize
fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet
fibers, buckwheat
fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered
cellulose,
bran fibers, bamboo fibers, and cellulose fiber.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as
humectants. Other humectants as described herein may also be used in
combination
with sodium alginate, glycerol or UPC or as an alternative.
Sodium carbonate is used as an alkaline buffering agent. Other buffering
agents as
described herein may also be used in combination with sodium carbonate or an
alternative.
Flavor example, a mixture of e.g. menthol and peppermint may be used. Of
course,
other flavors as described herein may be use as well, in combination with
menthol
and/or peppermint or replacing these. The flavor may be liquid or flavored or
a
combination, i.e. a liquid flavor and a powdered flavor is added.
Acesulfame potassium and/or sucralose may as an example be used as high
intensity
sweeteners. Other usable high intensity sweeteners described herein may be
used in
combination with or instead of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described
herein
may also be used in combination with or instead of potassium sorbate.
Silicon dioxide is used as a glidant. Other possible glidants include e.g.
magnesium
stearate, starch and talc.
Example 5D:
The pouch compositions are prepared from the ingredients in table 12 using
preparation method described in example 3.
The pouch compositions are filled into pouches as described in example 4
(pouch
material of examples lA was used, but 1B could also have been applied).
Pouches P30 P31 P32 P33 P34 P35 P36 P37 P38 P39
Amount of 9.6 9.6 9.6 9.6 9.6 9.6
9.6 4.8 7.2 12.0
nicotine mg mg mg mg mg mg mg mg mg mg
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Water content
28 28 28 28 28 28 28 28 28 28
[wt%]
Inorganic
1.0 1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0
cations [eq]*
Raw material Content in weight percent
Premix VI 6.4 6.4 6.4 6.4 6.4 6.4
6.4 3.2 4.8 8.0
CaCl2** - - - - 0.7 1.0 1.6
Calcium
1.9 - - - -
acetate**
Magnesium
- 1.7 - - -
acetate**
Calcium
- - 2.6 - -
lactate**
Magnesium
- 2.4 -
lactate**
FeC12** - - 1.5 -
ZnC12** - - - 1.6 -
A1C13** - - - - 1.6 -
Xylitol 18.7 18.9 18.0 18.2 19.1 19.0 19.0 21.9 20.5 17.6
Purified water 26 26 26 26 26 26 26
27.2 26.7 25.8
Wheat fiber 28 28 28 28 28 28 28 28 28 28
Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0
2.0 2.0 2.0 2.0
Sodium
5.0 5.0 5.0 5.0 5.0 5.0 5.0
5.0 5.0 5.0
carbonate
Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9
High intensity
1.0 1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0
sweetener
Potassium
0.1 0.1 0.1 0.1 0.1 0.1 0.1
0.1 0.1 0.1
sorb ate
Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0
2.0 2.0 2.0 2.0
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Total 100 100 100 100 100 100 100 100 100 100
Table 12: Pouch compositions.
*The inorganic cations are presented as equivalents relative to nicotine in
nicotine ion-
exchange combination.
**Multivalent cations may be provided as a hydrated salt, such as dihydrate,
tetrahydrate, hexahydrate etc. The weight% in the table are based on the non-
hydrated
salt.
Pouch content: 500 mg total.
Wheat fiber, trade name "Vitacel 600 WF plus". Other fibers may be used as
well,
such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice
fiber, maize
fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet
fibers, buckwheat
fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered
cellulose,
bran fibers, bamboo fibers, and cellulose fiber.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as
humectants. Other humectants as described herein may also be used in
combination
with sodium alginate, glycerol or HPC or as an alternative.
Sodium carbonate is used as an alkaline buffering agent. Other buffering
agents as
described herein may also be used in combination with sodium carbonate or an
alternative.
Flavor example, a mixture of e.g. menthol and peppermint may be used. Of
course,
other flavors as described herein may be use as well, in combination with
menthol
and/or peppermint or replacing these. The flavor may be liquid or flavored or
a
combination, i.e. a liquid flavor and a powdered flavor is added.
Acesulfame potassium and/or sucralose may as an example be used as high
intensity
sweeteners. Other usable high intensity sweeteners described herein may be
used in
combination with or instead of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described
herein
may also be used in combination with or instead of potassium sorbate.
Silicon dioxide is used as a glidant. Other possible glidants include e.g
magnesium
stearate, starch and talc.
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Example 5E:
The pouch compositions are prepared from the ingredients in table 13 using
preparation method described in example 3.
5 The pouch compositions are filled into pouches as described in
example 4 (pouch
material of examples lA was used, but 1B could also have been applied).
Pouches P40 P41 P42 P43 P44 P45 C4 C5
Amount of 9.6 9.6 9.6 9.6 9.6 9.6
9.6 9.6
nicotine mg mg mg mg mg mg mg mg
Water content
30 30 30 30 30 30 30
30
[wt%]
Inorganic divalent
0.75 1.0 1.5 0.75 1.0 1.5
cations [eq]*
Raw material Content in weight percent
Premix II 14.6 14.6 14.6 - -
14.6 -
Premix VI 6.4 6.4 6.4
6.4
CaCl2** 1.0 1.3 2.0 1.0 1.3 2.0
Xylitol 10.4 10.1 9.4 15.6 15.3
14.6 9.4 14.6
Purified water 25 25 25 28 28 28 25
28
Wheat fiber 30 30 30 30 30 30 30
30
Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0
2.0 2.0
Sodium carbonate 5.0 5.0 5.0 5.0 5.0 5.0
5.0 5.0
NaC1
2.0 2.0
Flavor 8.9 8.9 8.9 8.9 8.9 8.9
8.9 8.9
High intensity
1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0
sweetener
Potassium sorbate 0.1 0.1 0.1 0.1 0.1 0.1
0.1 0.1
Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0
2.0 2.0
Total 100 100 100 100 100 100
100 100
Table 13: Pouch compositions.
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*The inorganic divalent cations are presented as equivalents relative to
nicotine in
nicotine ion-exchange combination.
**Divalent cations may be provided as a hydrated salt, such as dihydrate,
tetrahydrate,
hexahydrate etc. The weight% in the table are based on the non-hydrated salt.
Pouch content: 500 mg total, i.e. nicotine cone 19.2 mg/g.
Wheat fiber, trade name "Vitacel 600 WF plus". Other fibers may be used as
well,
such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice
fiber, maize
fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet
fibers, buckwheat
fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered
cellulose,
bran fibers, bamboo fibers, and cellulose fiber.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as
humectants. Other humectants as described herein may also be used in
combination
with sodium alginate, glycerol or HPC or as an alternative.
Sodium carbonate is used as an alkaline buffering agent. Other buffering
agents as
described herein may also be used in combination with sodium carbonate or an
alternative.
Flavor example, a mixture of e.g. menthol and peppermint may be used. Of
course,
other flavors as described herein may be use as well, in combination with
menthol
and/or peppermint or replacing these. The flavor may be liquid or flavored or
a
combination, i.e. a liquid flavor and a powdered flavor is added.
Acesulfame potassium and/or sucralose may as an example be used as high
intensity
sweeteners. Other usable high intensity sweeteners described herein may be
used in
combination with or instead of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described
herein
may also be used in combination with or instead of potassium sorbate.
Silicon dioxide is used as a glidant. Other possible glidants include e.g.
magnesium
stearate, starch and talc.
Example 5F:
The pouch compositions are prepared from the ingredients in table 14 using
preparation method described in example 3.
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The pouch compositions are filled into pouches as described in example 4
(pouch
material of examples 1A was used, but 1B could also have been applied).
Pouches
P50 P51 P52 P53 P54 P55 C6 C7
9.6 9.6 9.6 9.6 9.6 9.6 9.6 9.6
Amount of nicotine
mg mg mg mg mg mg mg mg
Water content
15 25 40 30 30 10 30 30
[wf%]
Inorganic divalent
1.0 1.0 1.0 1.0 1.0 1.0
cations [eq]*
Raw material Content
in weight percent
Premix VI 6.4 6.4 6.4
6.4
Premix VII 5.5
5.5
Premix VIII 4.6
4.6
CaCl2** 1.3 1.3 1.3 1.3 1.3
1.3
Xylitol
45.3 25.3 4.3 15.6 16.1 49.3 21.9 17.4
Purified water 13 23 38 28.6 29 9
28.6 29
Wheat fiber 15 25 31 30 30 15 25
30
Sodium alginate 2.0 2.0 2.0 2.0 2.0
2.0 2.0 2.0
Sodium carbonate 5.0 5.0 5.0 5.0 5.0
5.0 5.0 5.0
Flavor 8.9 8.9 8.9 8.9 8.9
8.9 8.9 8.9
High intensity
1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0
sweetener
Potassium sorbate 0.1 0.1 0.1 0.1 0.1
0.1 0.1 0.1
Silicon dioxide 2.0 2.0 2.0 2.0 2.0
2.0 2.0 2.0
Total 100 100 100 100 100
100 100 100
Table 14: Pouch compositions.
*The inorganic divalent cations is presented as equivalents relative to
nicotine in
nicotine ion-exchange combination.
**Divalent cations may be provided as a hydrated salt, such as dihydrate,
tetrahydrate,
hexahydrate etc. The weight% in the table are based on the non-hydrated salt.
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Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.
Wheat fiber, trade name "Vitacel 600 WF plus". Other fibers may be used as
well,
such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice
fiber, maize
fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet
fibers, buckwheat
fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered
cellulose,
bran fibers, bamboo fibers, and cellulose fiber.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as
humectants. Other humectants as described herein may also be used in
combination
with sodium alginate, glycerol or TIPC or as an alternative.
Sodium carbonate is used as an alkaline buffering agent. Other buffering
agents as
described herein may also be used in combination with sodium carbonate or an
alternative.
Flavor example, a mixture of e.g. menthol and peppermint may be used. Of
course,
other flavors as described herein may be use as well, in combination with
menthol
and/or peppermint or replacing these. The flavor may be liquid or flavored or
a
combination, i.e. a liquid flavor and a powdered flavor is added.
Acesulfame potassium and/or sucralose may as an example be used as high
intensity
sweeteners. Other usable high intensity sweeteners described herein may be
used in
combination with or instead of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described
herein
may also be used in combination with or instead of potassium sorbate.
Silicon dioxide is used as a glidant. Other possible glidants include e.g.
magnesium
stearate, starch and talc.
Example 5G:
The pouch compositions are prepared from the ingredients in table 15 using
preparation method described in example 3.
The pouch compositions are filled into pouches as described in example 4
(pouch
material of examples lA was used, but 1B could also have been applied).
Pouches P60 P61 P62 P63 P64 P65 P66 P67 C8 C9
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Amount of 9.6 9.6 9.6 9.6 9.6 9.6 9.6
9.6 9.6 9.6
nicotine mg mg mg mg mg mg mg mg mg mg
Water
content 27 27 27 27 27 27 35 30 30 30
twt%]
Inorganic
divalent
1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 -
cations
[eq]*
Raw
Content in weight percent
material
Premix VI 6.4 6.4 6.4 6.4 6.4 6.4 6.4
6.4 6.4 6.4
CaC12** 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.3 -
Xylitol 5.0 - - 7.0 - 5.0 5.0 5.0
Isomalt - 21.3 -
Sorbitol - 21.3 -
Mannitol - 21.3 -
Maltitol - 21.3 -
Erythritol 16.3 - - 14.3 - 14.2 23.5 18.5
Purified
25 25 25 25 25 25 33 28 28 28
water
Wheat fiber 27 27 27 27 27 27 40.3 30 15 15
Sodium
2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
alginate
Sodium
5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0
carbonate
Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 5.0 7.0 7.0
NaC1 - 5.0 10.0
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High
intensity 1.0 1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0
sweetener
Potassium
0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1
sorb ate
Silicon
2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
dioxide
Total 100 100 100 100 100 100 100 100 100 100
Table 15: Pouch compositions.
*The inorganic divalent cations is presented as equivalents relative to
nicotine in
nicotine ion-exchange combination.
**Divalent cations may be provided as a hydrated salt, such as dihydrate,
tetrahydrate,
5 hexahydrate etc. The weight% in the table are based on the non-
hydrated salt.
Pouch content: 500 mg total, i.e. nicotine cone 19.2 mg/g.
Wheat fiber, trade name "Vitacel 600 WF plus". Other fibers may be used as
well,
such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice
fiber, maize
10 fibers, oat fibers, tomato fibers, barley fibers, rye fibers,
sugar beet fibers, buckwheat
fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered
cellulose,
bran fibers, bamboo fibers, and cellulose fiber.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as
humectants. Other humectants as described herein may also be used in
combination
15 with sodium alginate, glycerol or HPC or as an alternative.
Sodium carbonate is used as an alkaline buffering agent. Other buffering
agents as
described herein may also be used in combination with sodium carbonate or an
alternative.
Flavor example, a mixture of e.g. menthol and peppermint may be used. Of
course,
20 other flavors as described herein may be use as well, in
combination with menthol
and/or peppermint or replacing these. The flavor may be liquid or flavored or
a
combination, i.e. a liquid flavor and a powdered flavor is added.
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Acesulfame potassium and/or sucralose may as an example be used as high
intensity
sweeteners. Other usable high intensity sweeteners described herein may be
used in
combination with or instead of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described
herein
may also be used in combination with or instead of potassium sorbate.
Silicon dioxide is used as a glidant. Other possible glidants include e.g.
magnesium
stearate, starch and talc.
Example 5H:
The pouch compositions are prepared from the ingredients in table 16 using
preparation method described in example 3.
The pouch compositions are filled into pouches as described in example 4
(pouch
material of examples lA was used, but 1B could also have been applied).
Pouches
P70 P71 P72 P73 P74 P75 P76 P77
9.6 9.6 9.6 9.6 9.6 9.6 9.6 9.6
Amount of nicotine
mg mg mg mg mg mg mg mg
Water content [wt%] 27 27 27 20 20
35 20 35
Inorganic divalent cations
1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0
[eq]*
Raw material Content in weight percent
Premix VI 6.4 6.4 6.4 6.4 6.4
6.4 6.4 6.4
CaCl2** 1.3 1.3 1.3 1.3 1.3
1.3 1.3 1.3
Xylitol
5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0
Erythritol
18.2 18.2 18.2 42.2 22.2 17.2 22.2 17.2
Purified water 25 25 25 18 18 33 18 33
Wheat fiber 10 30 20
Oat fiber 27
30 20
Pea Fiber 27
Powdered Cellulose 27
Sodium alginate 2.0 2.0 2.0 2.0 2.0
2.0 2.0 2.0
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Sodium carbonate 5.0 5.0 5.0 5.0 5.0
5.0 5.0 5.0
Flavor 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0
High intensity sweetener 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0
Potassium sorbate 0.1 0.1 0.1 0.1 0.1
0.1 0.1 0.1
Silicon dioxide 2.0 2.0 2.0 2.0 2.0
2.0 2.0 2.0
Total 100 100 100 100 100 100 100 100
Table 16: Pouch compositions.
*The inorganic divalent cations is presented as equivalents relative to
nicotine in
nicotine ion-exchange combination.
**Divalent cations may be provided as a hydrated salt, such as dihydrate,
tetrahydrate,
hexahydrate etc. The weight% in the table are based on the non-hydrated salt.
Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.
Wheat fiber, trade name "Vitacel 600 WF plus" or "Vitacel 200WF".
Powdered cellulose, trade name "Vitacel LOU" or "Vitacel L700G".
Oat fiber, trade name "Vitacel HF 600".
Pea fiber, trade name "Vitacel EF150".
Other fibers may be used as well, such as water-insoluble plant fibers, such
as oat
fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers,
barley fibers, rye
fibers, sugar beet fibers, buckwheat fibers, potato fibers, powdered
cellulose, cellulose
fibers, apple fibers, cocoa fibers, bamboo fibers, bran fibers, and cellulose
fiber.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as
humectants. Other humectants as described herein may also be used in
combination
with sodium alginate, glycerol or HPC or as an alternative.
Sodium carbonate is used as an alkaline buffering agent. Other buffering
agents as
described herein may also be used in combination with sodium carbonate or an
alternative.
Flavor example, a mixture of e.g. menthol and peppermint may be used. Of
course,
other flavors as described herein may be use as well, in combination with
menthol
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and/or peppermint or replacing these. The flavor may be liquid or flavored or
a
combination, i.e. a liquid flavor and a powdered flavor is added.
Acesulfame potassium and/or sucralose may as an example be used as high
intensity
sweeteners. Other usable high intensity sweeteners described herein may be
used in
combination with or instead of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described
herein
may also be used in combination with or instead of potassium sorbate.
Silicon dioxide is used as a glidant. Other possible glidants include e.g.
magnesium
stearate, starch and talc.
Example 51:
The pouch compositions are prepared from the ingredients in table 17 using
preparation method described in example 3.
The pouch compositions are filled into pouches as described in example 4
(pouch
material of examples lA was used, but 1B could also have been applied).
Pouches P80 P81 P82 P83 P84 P85 P86 P87 P88
9.6 9.6 9.6 9.6 9.6 9.6
9.6 9.6 9.6
Amount of nicotine
mg mg mg mg mg mg mg mg mg
Water content
28 28 28 28 28 35 28 28 28
[wt%]
Inorganic divalent
1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0
cations [eq]*
Raw material Content in weight percent
NPR (16%) 12.1 12.1 12.1 12.1 12.1
12.1 12.1 12.1 12.1
CaCl2** 1.3 1.3 1.3 1.3 1.3 1.3
1.3 1.3 1.3
Xylitol 5.0 5.0
5.0 5.0
Isomalt 13.5
Sorbitol 13.5
Mannitol 13.5
Maltitol 13.5
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Erythritol 8.5 - - 8.5
8.5 8.5
Purified water 28 28 28 28 28 35 28
28 28
Wheat fiber 28 28 28 28 28 34.5 -
Oat fiber 28
Pea Fiber 28
Powdered
28
Cellulose
Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0
2.0 2.0 2.0
Sodium carbonate 5.0 5.0 5.0 5.0 5.0 5.0
5.0 5.0 5.0
Flavor 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0
High intensity
1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0
sweetener
Potassium sorbate 0.1 0.1 0.1 0.1 0.1 0.1
0.1 0.1 0.1
Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0
2.0 2.0 2.0
Total 100 100 100 100 100 100 100 100 100
Table 17: Pouch compositions.
*The inorganic divalent cations are presented as equivalents relative to
nicotine in
nicotine ion-exchange combination.
**Divalent cations may be provided as a hydrated salt, such as dihydrate,
tetrahydrate,
hexahydrate etc. The weight% in the table are based on the non-hydrated salt.
Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.
Wheat fiber, trade name "Vitacel 600 WF plus" or "Vitacel 200WF".
Powdered cellulose, trade name "Vitacel LOO" or "Vitacel L700G".
Oat fiber, trade name "Vitacel HF 600".
Pea fiber, trade name "Vitacel EF150".
Other fibers may be used as well, such as water-insoluble plant fibers, such
as oat
fibers, pea fibers, rice fiber, maize fibers, oat fibers, tomato fibers,
barley fibers, rye
fibers, sugar beet fibers, buckwheat fibers, potato fibers, powdered
cellulose, cellulose
fibers, apple fibers, cocoa fibers, bamboo fibers, bran fibers, and cellulose
fiber.
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Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as
humectants. Other humectants as described herein may also be used in
combination
with sodium alginate, glycerol or HPC or as an alternative.
Sodium carbonate is used as an alkaline buffering agent. Other buffering
agents as
5 described herein may also be used in combination with sodium
carbonate or an
alternative.
Flavor example, a mixture of e.g. menthol and peppermint may be used. Of
course,
other flavors as described herein may be use as well, in combination with
menthol
and/or peppermint or replacing these. The flavor may be liquid or flavored or
a
10 combination, i.e. a liquid flavor and a powdered flavor is
added.
Acesulfame potassium and/or sucralose may as an example be used as high
intensity
sweeteners. Other usable high intensity sweeteners described herein may be
used in
combination with or instead of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described
herein
15 may also be used in combination with or instead of potassium
sorbate.
Silicon dioxide is used as a glidant. Other possible glidants include e.g
magnesium
stearate, starch and talc.
Example 5J:
20 The pouch compositions are prepared from the ingredients in
table 18 using
preparation method described in example 3.
The pouch compositions are filled into pouches as described in example 4
(pouch
material of examples lA was used, but 1B could also have been applied).
Pouches
P90 P91 P92 P93 P94 P95 P96 P97 P98
Amount of 9.6 9.6 9.6 9.6 9.6 9.6
9.6 9.6 9.6
nicotine
mg mg mg mg mg mg mg mg mg
Water content
30 30 27 27 27 30 30 30 30
[wt%]
Inorganic divalent
1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0
cations [eq]*
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Raw material Content in weight percent
NPR (16%) 7.0 12.1 12.1 12A 12A
12.1 12.1 12.1 12.1
NBT 2.3 -
CaCl2** 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.3
Xylitol 10.4 10.1 8.6 11.6 11.6 12.6 7.6 7.6 11.5
Purified water 30 30 27 27 27 30 30
30 30
Wheat fiber 30 30 27 27 27 30 30
30 30
Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0 -
Glycerol - 2.0 -
Hydroxypropyl
cellulose
Sodium carbonate 5.0 2.5 10.0 3.5 - -
5.0 5.0 5.0
Sodium hydrogen-
carbonate
Trometamol - 7.0 -
Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 7.0
High intensity
1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0
sweetener
Potassium sorbate 0.1 0.1 0.1 0.1 0.1 0.1
0.1 0.1 0.1
Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0
2.0 2.0 2.0
Total 100 100 100 100 100 100 100 100 100
Table 18: Pouch compositions.
*The inorganic divalent cations are presented as equivalents relative to
nicotine in
nicotine ion-exchange combination.
**Divalent cations may be provided as a hydrated salt, such as dihydrate,
tetrahydrate,
hexahydrate etc. The weight% in the table are based on the non-hydrated salt.
Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.
Wheat fiber, trade name "Vitacel 600 WF plus". Other fibers may be used as
well,
such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice
fiber, maize
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fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet
fibers, buckwheat
fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered
cellulose,
bran fibers, bamboo fibers, and cellulose fiber.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as
humectants. Other humectants as described herein may also be used in
combination
with sodium alginate, glycerol or HPC or as an alternative.
Sodium carbonate is used as an alkaline buffering agent. Other buffering
agents as
described herein may also be used in combination with sodium carbonate or an
alternative.
Flavor example, a mixture of e.g. menthol and peppermint may be used. Of
course,
other flavors as described herein may be use as well, in combination with
menthol
and/or peppermint or replacing these. The flavor may be liquid or flavored or
a
combination, i.e. a liquid flavor and a powdered flavor is added.
Acesulfame potassium and/or sucralose may as an example be used as high
intensity
sweeteners. Other usable high intensity sweeteners described herein may be
used in
combination with or instead of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described
herein
may also be used in combination with or instead of potassium sorbate.
Silicon dioxide is used as a glidant. Other possible glidants include e.g.
magnesium
stearate, starch and talc.
Example 5K:
The pouch compositions are prepared from the ingredients in table 19 using
preparation method described in example 3.
The pouch compositions are filled into pouches as described in example 4
(pouch
material of examples lA was used, but 1B could also have been applied).
Pouches
100 101 102 103 104 105 106 107 108
Amount of 9.6 9.6 9.6 9.6 9.6 9.6
9.6 9.6 9.6
nicotine
mg mg mg mg mg mg mg mg mg
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78
Water content
30 30 27 27 27 30 30 30 30
rwt%1
Inorganic divalent
1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0
cations [eq]*
Raw material Content in weight percent
Premix VI 3.7 6.4 6.4 6.4 6.4 6.4
6.4 6.4 6.4
NBT 2.3 -
CaCl2** 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.3 1.3
Xylitol 14.7 17.8 13.3 16.3 16.3 20.3 15.3 15.3 17.3
Purified water 29 28 25 25 25 28 28
28 28
Wheat fiber 30 30 30 30 30 30 30
30 30
Sodium alginate 2.0 2.0 2.0 2.0 2.0 2.0 -
Glycerol - 2.0 -
Hydroxypropyl
cellulose
Sodium carbonate 5.0 2.5 10.0 3.5 - -
5.0 5.0 5.0
Sodium
- 3.5 -
hydrogencarbonate
Trometamol - 7.0 -
Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9
High intensity
1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0
sweetener
Potassium sorbate 0.1 0.1 0.1 0.1 0.1 0.1
0.1 0.1 0.1
Silicon dioxide 2.0 2.0 2.0 2.0 2.0 2.0
2.0 2.0 2.0
Total 100 100 100 100 100 100 100 100 100
Table 19: Pouch compositions.
*The inorganic divalent cations are presented as equivalents relative to
nicotine in
nicotine ion-exchange combination.
**Divalent cations may be provided as a hydrated salt, such as dihydrate,
tetrahydrate,
hexahydrate etc. The weight% in the table are based on the non-hydrated salt.
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Pouch content: 500 mg total, i.e. nicotine conc 19.2 mg/g.
Wheat fiber, trade name "Vitacel 600 WF plus". Other fibers may be used as
well,
such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice
fiber, maize
fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet
fibers, buckwheat
fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered
cellulose,
bran fibers, bamboo fibers, and cellulose fiber.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as
humectants. Other humectants as described herein may also be used in
combination
with sodium alginate, glycerol or TIPC or as an alternative.
Sodium carbonate is used as an alkaline buffering agent. Other buffering
agents as
described herein may also be used in combination with sodium carbonate or an
alternative.
Flavor example, a mixture of e.g. menthol and peppermint may be used. Of
course,
other flavors as described herein may be use as well, in combination with
menthol
and/or peppermint or replacing these. The flavor may be liquid or flavored or
a
combination, i.e. a liquid flavor and a powdered flavor is added.
Acesulfame potassium and/or sucralose may as an example be used as high
intensity
sweeteners. Other usable high intensity sweeteners described herein may be
used in
combination with or instead of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described
herein
may also be used in combination with or instead of potassium sorbate.
Silicon dioxide is used as a glidant. Other possible glidants include e.g.
magnesium
stearate, starch and talc.
Example 5L:
The pouch compositions are prepared from the ingredients in table 20 using
preparation method described in example 3.
The pouch compositions are filled into pouches as described in example 4
(pouch
material of examples lA was used, but 1B could also have been applied).
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P P PP P P P P
Pouches C10 C11 C12
110 111 112 113 114 115 116 117
Amount
9.6 9.6 9.6 9.6 9.6 9.6 8.0 8.0 9.6 9.6 8.0
of
mg mg mg mg mg mg mg mg mg mg mg
nicotine
Water
content 30 30 30 30 30 30 29 29 30 30 29
twt%]
Inorga-
nic
divalent 0.75 1.0 1.5 0.75 1.0 1.5 2.0 5.0 -
cations
[eq]*
Raw
Content in weight percent
material
Premix
14.6 14.6 14.6 -
- 12.1 12.1 14.6 - 12.1
II
Premix
- 6.4 6.4 6.4 - - 6.4 -
VI
CaC12** 1.0 1.3 2.0 1.0 1.3 2.0 2.2 5.5 -
Xylitol 12.4 12.1 11.4 17.6 17.3 16.6 5.0 5.0 13.4 18.6 5.0
Erythri-
- 13.3 6.2 - - 16.9
to!
Purified
25 25 25 28 28 28 25 25 25 28 25
water
Wheat
30 30 30 30 30 30 - - 30 30 -
fiber
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Powde-
red
- 30 30 - -
30
Cellu-
lose
Sodium
carbo- 5.0 5.0 5.0 5.0 5.0 5.0 4.4 8.2 5.0 5.0 3.0
nate
Flavor 8.9 8.9 8.9 8.9 8.9 8.9 4.9 4.9 8.9 8.9 4.9
High
intensity
1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0
sweete-
ner
Potas-
sium 0.1 0.1 0.1 0.1 0.1 0.1 0.1
0.1 0.1 0.1 0.1
sorb ate
Silicon
2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
dioxide
Total 100 100 100 100 100 100 100 100 100 100 100
Table 20: Pouch compositions.
*The inorganic divalent cations are presented as equivalents relative to
nicotine in
nicotine ion-exchange combination.
**Divalent cations may be provided as a hydrated salt, such as dihydrate,
tetrahydrate,
hexahydrate etc. The weight% in the table are based on the non-hydrated salt.
Pouch content: 500 mg total, i.e. nicotine cone 19.2 mg/g (16 mg/g for samples
P116,
P117 and C12).
Wheat fiber, trade name "Vitacel 600 WF plus". Powdered Cellulose, trade name
"Powdered Cellulose L700G". Other fibers may be used as well, such as water-
insoluble plant fibers, such as oat fibers, pea fibers, rice fiber, maize
fibers, oat fibers,
tomato fibers, barley fibers, rye fibers, sugar beet fibers, buckwheat fibers,
potato
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fibers, cellulose fibers, apple fibers, cocoa fibers, bran fibers, bamboo
fibers, and
cellulose fiber.
Sodium carbonate is used as an alkaline buffering agent. Other buffering
agents as
described herein may also be used in combination with sodium carbonate or an
alternative.
Flavor example, a mixture of e.g. menthol and peppermint may be used. Of
course,
other flavors as described herein may be use as well, in combination with
menthol
and/or peppermint or replacing these. The flavor may be liquid or flavored or
a
combination, i.e. a liquid flavor and a powdered flavor is added.
Acesulfame potassium and/or sucralose may as an example be used as high
intensity
sweeteners. Other usable high intensity sweeteners described herein may be
used in
combination with or instead of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described
herein
may also be used in combination with or instead of potassium sorbate.
Silicon dioxide is used as a glidant. Other possible glidants include e.g.
magnesium
stearate, starch and talc.
Example 51µ1:
The pouch compositions are prepared from the ingredients in table 21 using
preparation method described in example 3.
The pouch compositions are filled into pouches as described in example 4
(pouch
material of examples lA was used, but 1B could also have been applied).
Pouches
120 121 122 123 124 125 126 127 128 129
Amount
9.6 9.6 9.6 9.6 9.6 9.6 9.6
9.6 9.6 9.6
of
mg mg mg mg mg mg mg mg mg mg
nicotine
Water
content 30 30 30 30 30 30 27 27 27 27
[wt.%]
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Inorganic
divalent
2.0 3.0 4.0 2.0 3.0 4.0 7.5 7.5 7.5 7.5
cations
[eg]*
Raw
Content in weight percent
material
Premix II 14.6 14.6 14.6 - - 14.6 -
Premix
6.4 6.4 6.4 - 6.4 6.4 6.4
VI
CaCl2** 2.6 3.9 5.2 2.6 3.9 5.2 10.0 10.0 10.0 10.0
Xylitol 8.8 7.5 6.2 14.0 12.7 11.4 7.4 12.6 11.0 8.5
Purified
25 25 25 28 28 28 22 25 25 25
water
Wheat
30 30 30 30 30 30 27 27 27 27
fiber
Sodium
2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
alginate
Sodium
5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0
carbonate
Flavor 8.9 8.9 8.9 8.9 8.9 8.9 8.9 8.9 10.5 13.0
High
intensity 1.0 1.0 1.0 1.0 1.0 1.0 1.0
1.0 1.0 1.0
sweetener
Potassiu
0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1
m sorbate
Silicon
2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
dioxide
Total 100 100 100 100 100 100 100 100 100 100
Table 21: Pouch compositions.
*The inorganic divalent cations are presented as equivalents relative to
nicotine in
nicotine ion-exchange combination.
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**Divalent cations may be provided as a hydrated salt, such as dihydrate,
tetrahydrate,
hexahydrate etc. The weight% in the table are based on the non-hydrated salt.
Pouch content: 500 mg total, i.e. nicotine cone 19.2 mg/g.
Wheat fiber, trade name "Vitacel 600 WF plus-. Other fibers may be used as
well,
such as water-insoluble plant fibers, such as oat fibers, pea fibers, rice
fiber, maize
fibers, oat fibers, tomato fibers, barley fibers, rye fibers, sugar beet
fibers, buckwheat
fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, powdered
cellulose,
bran fibers, bamboo fibers, and cellulose fiber.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as
humectants. Other humectants as described herein may also be used in
combination
with sodium alginate, glycerol or HPC or as an alternative.
Sodium carbonate is used as an alkaline buffering agent. Other buffering
agents as
described herein may also be used in combination with sodium carbonate or an
alternative.
Flavor example, a mixture of e.g. menthol and peppermint may be used. Of
course,
other flavors as described herein may be use as well, in combination with
menthol
and/or peppermint or replacing these. The flavor may be liquid or flavored or
a
combination, i.e. a liquid flavor and a powdered flavor is added.
Acesulfame potassium and/or sucralose may as an example be used as high
intensity
sweeteners. Other usable high intensity sweeteners described herein may be
used in
combination with or instead of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described
herein
may also be used in combination with or instead of potassium sorbate.
Silicon dioxide is used as a glidant. Other possible glidants include e.g.
magnesium
stearate, starch and talc.
Example 6A: Release experiment and varying salts.
The release experiment was performed by adding an amount of NPR (16%) and
varying equivalent of CaCl2 to 900 mL of water corresponding to a nicotine
concentration of 28 mg/L. The equivalents of CaCl2 are relative to nicotine.
The
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temperature of the water was 25 degrees Celsius throughout the experiment and
stirring of 100 rpm was applied throughout the experiment. pH was measured at
experiment start and end. The pH was in all experiments below 7.0 at both the
start
and end of the experiment.
5 A relative low nicotine concentration is used in order to
reduce the impact of
equilibrium on both the release rate and effective release of nicotine from
the ion-
exchange resin.
Samples were taken out at varying timepoints and analyzed for nicotine content
using
standard HPLC. The results are presented as percentage of nicotine released.
No 1 eq 10 eq 1 eq 10 eq
Salt
Salt NaCl NaC1 CaC12 CaCl2
Minutes Released nicotine (%)
1 12.4 - - 46.3 -
2 15.9 24.4 43.8 - 80.3
3 - - 58.4
4 18.1 - - - -
8 20.2 - 69.2
11 20.9 - - 72.6 -
13 - 28.1 51.9 89.9
14 21.8 - - 75.0 -
17 22.4 - - 76.5 -
20 23.1 - 78.2
23 - 29.9 52.9
25 24.0 - - -
30 24.8 - - -
33 - 30.1 54.5 90.4
35 25.7 - - -
40 26.5 - - -
45 27.2 - - 81.1 -
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60 28.8 82.0
Table 22: Release of nicotine over time in the presence of varying salts and
varying
equivalents of cations.
Evaluation: the result shows that the presence of CaCl2 significantly
increases the
release of nicotine from NPR. Increasing the amount of CaCl2 result in an
increased
release of nicotine. The presence of CaCl2 increases both the initial release
rate and
seems to also increase the effective release of nicotine.
Furthermore, the results show that NaCl has a much lower effect on the release
of
nicotine, thus high amount of NaCl are needed in order to achieve comparable
release
of nicotine in the presence of for example 1 eq. of CaCl2.
Example 6B: Release experiment using NPR and varying equivalents of CaCl2.
The release experiment was performed by adding NPR (16%) and varying
equivalent
of CaCl2 to a volume of water corresponding to a nicotine concentration of 28
mg/L.
The equivalents of CaCl2 are relative to nicotine. The temperature of the
water was 25
degrees Celsius throughout the experiment and stirring of 100 rpm was applied
throughout the experiment. pH was measured at experiment start and end. The pH
was
in all experiments below 7.0 at both the start and end of the experiment.
A relative low nicotine concentration is used in order to reduce the impact of
equilibrium on both the release rate and effective release of nicotine from
the ion-
exchange resin.
Samples were taken out at varying timepoints and analyzed for nicotine content
using
standard HPLC. The result is presented as percentage of nicotine released.
0.25 0.5
CaCl2 0 eq 0.1 eq 0.75 eq 1
eq 4 eq
eq eq
Minutes Released nicotine (%)
1 12.4 17.7 25.0 30.5 38.5 46.3 59.1
2 15.9 22.0 39.7
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3 - - 33.9 - 51.7 58.4
71.8
4 18.1 24.3 46.1
- - 38.6 - - 59.3 76.8
7 - - 42.4 - - 64.0 -
8 20.2 26.6 - 53.3 - 69.2
79.9
9 43.3 66.7
11 20.9 27.8 44.1 56.4 68.9
72.6 82.4
13 - - 46.0 - - 71.0 -
14 21.8 28.7 - 58.9 - 75.0
83.9
- - 45.9 - - 73.0 -
17 22.4 29.3 - 61.0 74.4 76.5
84.7
18 47.2
23.1 30.3 47.5 62.4 76.3 78.2 85.0
24.0 31.1 - 64.4 - - -
24.8 31.8 49.3 65.8 - - -
25.7 32.6 66.8
26.5 33.2 67.8
27.2 33.8 50.6 69.2 80.2 81.1 87.3
60 28.8 35.0 51.7 69.2 81.1
82_0 88.1
Table 23: Shows the percentage of nicotine released from NPR at different
timepoints
in the presence of varying equivalent of CaCl2.
Evaluation: the result shows that the presence of CaCl2 significantly
increases the
5 release of nicotine from NPR. Increasing the amount of CaCl2
result in an increased
release of nicotine. The presence of CaCl2 increases both the initial release
rate and
seems to also increase the effective release of nicotine.
Example 6C: Release experiment using NPR and varying equivalents of MgC12.
10 The release experiment was performed by adding NPR (16%) and
varying equivalents
of MgCl2 to a volume of water corresponding to a nicotine concentration of 28
mg/L.
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The equivalents of MgC12 are relative to nicotine. The temperature of the
water was
25 degrees Celsius throughout the experiment and stirring of 100 rpm was
applied
throughout the experiment. pH was measured at experiment start and end. The pH
was
in all experiments below 7.0 at both the start and end of the experiment.
A relative low nicotine concentration is used in order to reduce the impact of
equilibrium on both the release rate and effective release of nicotine from
the ion-
exchange resin.
Samples were taken out at varying timepoints and analyzed for nicotine content
using
standard HPLC. The result is presented as percentage of nicotine released.
0.25 0.75
MgCl2 0 eq 0.1 eq 0.5 eq 1 eq 2 eq
4 eq
eq eq
Minute
Released nicotine (/0)
1 12.4 16.8 23.2 33.7 40.6 42.3
53.7 63.0
3 22.9 32.2 44.1 52.2 55.3
66.5 73.6
5 25.8 37.0 49.9 58.1 62.4
72.2 79.4
7 27.6 39.9 54.0 62.4 66.7
74.8 81.3
9 28.4 41.6 56.7 64.8 69.3
76.5 83.2
11 20.9 29.1 43.0 58.6 67.5 71.7
78.2 83.9
13 29.9 44.5 60.2 70.1 73.0
79.7 85.1
30.5 44.8 61.6 71.2 74.2 80.4 87.0
23.1 31.5 47.2 64.5 72.8 76.5 82.1 87.5
24.0 32.5 47.7 65.7 75.8 77.7 83.8 87.9
24.8 33.2 48.8 68.1 78.2 88.1
Table 24: Shows the percentage of nicotine released from NPR at different
timepoints
in the presence of varying equivalents of MgCl2.
Evaluation: the result shows that the presence of MgCl2 significantly
increases the
15 release of nicotine from NPR. Increasing the amount of MgCl2
result in an increased
release of nicotine. The presence of MgCl2 increases both the initial release
rate and
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seems to also increase the effective release of nicotine. The results are
comparable to
the result presented in example 6B.
Example 6D: Release experiment using 1 equivalent of CaCl2 and nicotine premix
having varying content of nicotine.
The release experiment was performed by adding nicotine premix having varying
content of nicotine and 1 equivalent of CaCl2 to a volume of water, whereby a
corresponding nicotine concentration of 28 mg/L is obtained. The equivalent of
CaCl2
is relative to nicotine. rt he temperature of the water was 25 degrees Celsius
throughout
the experiment and stirring of 150 rpm was applied throughout the experiment.
pH was
measured at experiment start and end. The pH was in all experiments below 7.0
at both
the start and end of the experiment.
A relative low nicotine concentration is used in order to reduce the impact of
equilibrium on both the release rate and effective release of nicotine from
the ion-
exchange resin.
Samples were taken out at varying timepoints and analyzed for nicotine content
using
standard HPLC. The result is presented as percentage of nicotine released.
Ingredients
Premix II
II VI VI VII VII VIII VIII
CaCl2 1 eq. 1 eq. 1 eq.
1 eq.
Min. Released nicotine (/o)
1 2.1 9.1 37.2 56.3 43.8
55.7 58.3 69.6
2 3.0 14.7 44.9 66.9 53.4
66.0 66.2 78.7
3 4.0 19.9 48.9 71.4 57.4
73.4 70.1 82.6
4 4.9 24.7 51.8 76.8 60.1
77.8 72.0 85.9
5 5.7
29.8 53.7 79.5. 62.2 81.4 73.0 88.4
6 6.5 33.7 54.4 81.6 63.0
84.1 74.7 90.3
7 7.1 38.6 55.4 83.1 64.4
86.2 75.0 92.3
8 8.0 42.0 56.1 84.8 65.2
88.9 75.4 92.9
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9 8.4 46.4 56.9 86.3 65.5
90.5 75.7 94.5
10 9.0 49.9 57.4 87.3 66.1
91.1 76.0 94.7
11 53.1 58.0 88.0 66.5
92.6 76.5 95.7
12 55.6 58.4 89.2 67.3
93.4 96.3
13 57.7 58.5 89.9 66.9
93.8 77.0 96.9
14 60.5 58.9 90.9 67.3
95.0 97.3
15 11.8 62.0 59.6 91.6 68.2
95.8 77.3 97.3
Table 25: Shows the percentage of nicotine released from nicotine premix at
different
timepoints in the presence of 1 equivalent of MgCl2.
Evaluation: the result shows that the presence of CaCl2 significantly
increases the
5 release of nicotine from premixes. The presence of CaC12
increases both the initial
release rate and seems to also increase the effective release of nicotine.
Furthermore,
the results demonstrate that increasing the nicotine content of the premixes
also
increases the nicotine release.
Example 6E: Release experiment using 1 equivalent of A1C13.
The release experiment was performed by adding NPR (16%) and 1 equivalent of
A1C13 to a volume of water corresponding to a nicotine concentration of 28
mg/L. The
equivalents are relative to nicotine. The temperature of the water was 25
degrees
Celsius throughout the experiment and stirring of 150 rpm was applied
throughout the
experiment. pH was measured at experiment start and end. The pH was in all
experiments below 7.0 at both the start and end of the experiment.
A relative low nicotine concentration is used in order to reduce the impact of
equilibrium on both the release rate and effective release of nicotine from
the ion-
exchange resin.
Samples were taken out at varying timepoints and analyzed for nicotine content
using
standard HPLC. The result is presented as percentage of nicotine released.
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No 1 eq
Salt
Salt AlC13
Released
Minutes
nicotine (3/0)
1 11.1 39.9
3 14.5 49.4
16.1 55.4
8 18.2 60.9
11 19.7 64.4
20.0 68.4
21.1 71.4
21.5 74.0
22.4 75.4
Table 24: Shows the percentage of nicotine released from NPR at different
timepoints
in the presence of 1 equivalent of A1C13.
Evaluation: the results demonstrate that the presence of 1 equivalent of AlC13
5 significantly increases the release of nicotine from NPR. The
presence of A1C13
increases both the initial release rate and seems to also increase the
effective release
of nicotine.
Example 7A: Pouch release experiments (in vitro)
10 The release properties of the pouches were tested in an in
vitro experiment.
Reaction tubes having a diameter approx. 2 cm and containing 10 mL of 0.02 M
potassium dihydrogen phosphate-buffer (pH adjusted to 7.4) were warmed to 37
degrees Celsius. One reaction tuber per timepoint was used.
A pouch was submerged in the buffer of the first reaction tube using tweezers.
After a
15 specified time period, the pouch was captured with the tweezer
and gently swirled in
the buffer before being removed from the first reaction tube and added to the
next
reaction tube, representing the next time point. The procedure was repeated
until the
desired number of time points had been tested.
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The whole release experiment was performed at 37 degrees Celsius. No stirring
or
shaken was applied during the release experiment.
The amount of release nicotine was determined by analyzing the buffer samples
at the
different timepoints using standard HPLC.
Example 8A: Release experiment on pouches
The release experiment was performed as described in example 7A.
Pouch C4 P40 P42 CS P43 P45
Premix II II II VI VI VI
CaCl2 - 0.75 eq 1.5 eq - 0.75 eq 1.5 eq
NaCl 2.9 eq - - 2.9 eq -
Min. Released nicotine (/o)
2 13.8 12.9 32.4 20.8 24.0 39.3
5 25.7 26.0 49.6 39.8 42.9 62.5
10 37.5 40.3 66.0 59.0 61.7 78.8
30 60.4 62.3 79.9 79.4 82.6 90.3
Table 27A: Shows the percentage of nicotine released from nicotine pouches at
different timepoints in the presence of varying equivalents of CaCl2.
Pouch C10 P110 C11 P113 C12 P116 P117
Premix II II VI VI II II II
0.75 0.75
CaCl2 2.0 eq 5.0 eq
eq eq
NaCl
Min. Released nicotine (/0)
2 16.2 29.5 26.9 38.7 22.1 26.4 35.4
5 28.6 50.9 47.4 58.2 36.3 40.2 55.5
10 42.0 64.8 66.0 74.8 52.1 56.0 77.2
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30 59.2 78.7 79.5 92.2 73.7 82.1 99.2
Table 27B: Shows the percentage of nicotine released from nicotine pouches at
different timepoints in the presence of varying equivalents of CaCl2.
Evaluation: comparing P110 and P113 with C10 and C11 respectively, the result
shows that the presence of CaCl2 increases the release of nicotine from
pouches. This
is also confirmed by comparison of P116 with C12. The presence of CaCl2
increases
both the initial release rate and seems to also increase the effective release
of nicotine.
Comparing P40 and P42, and comparing P116 and P117, demonstrate that
increasing
the amount of CaCl2 in a pouch also increases the nicotine release from the
pouch.
Also, it is noted that desirable improved release results are demonstrated to
be obtained
with various formulations including different fibers, here wheat fiber and
powdered
cellulose.
Furthermore, the results demonstrate that increasing the nicotine content of
the
premixes also increases the nicotine release from the pouches, comparing P40
with
P43, P42 with P45 and P110 with P113.
Finally, it is noted that in order to obtain a release being comparable to the
release
obtained from pouches comprising only 0.75 eq CaCl2, a much higher amount of
NaCl
will be needed, here at least 2.9 eq NaCl required to obtain a release being
comparable
to 0.75 eq CaCl2 (see C4, C5, P40 and P43).
Example 9A: User evaluation.
The produced pouches of the invention were evaluated and found highly suitable
as
delivery vehicles of nicotine in that they provide a favorable release of
nicotine and at
the same time are pleasant to the user, e.g. with respect to a desirable
mouthfeel such
as a moist and moldable texture and a desirable taste.
Example 9B: User evaluation.
The pouch products P03, P44 and P117 were evaluated with respect to perceived
effect
from nicotine and mouthfeel.
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WO 2022/100805
PCT/D1(2021/050334
94
Evaluation of perceived effect from nicotine and mouthfeel is performed as
described
in the following.
Perceived effect from nicotine and mouthfeel was evaluated by a test panel of
4 trained
assessors. Each assessor evaluates all samples twice. Average evaluations are
estimated.
The pouch product P03,P44 and P117 were evaluated to have a fast onset of
action and
a high perceived effect from nicotine by all four assessors. Also, all four
assessors
evaluated the pouch products to have a desirable mouthfeel, i.e. the pouches
were
found to be moist and have a desirable taste.
Similarly, the pouches, P08 and P127, were evaluated. These pouches were
evaluated
to have a fast onset of action and a high perceived effect from nicotine by
all four
assessors. However, the pouches were found to provide a less desirable
mouthfeel, the
pouches being perceived as somewhat dry, adhering to the oral mucosa and/or as
having a poor taste or less desirable taste, i.e. too salty.
Pouches comparable to P127 but comprising higher amounts of flavor, were also
evaluated, i.e. P128 and P129. Despite their increased flavor levels compared
to P127,
these pouches were also perceived as being dry and adhering to the oral
mucosa.
Furthermore, the taste was also for these pouches found to be less desirable,
as notes
of saltiness were still perceived and the flavor profile was perceived as
imbalanced.
These observations indicate that the less desirable mouth feel and taste
effects
associated with high levels of inorganic divalent cations cannot be offset by
increasing
the level of flavor in the pouch composition. I.e. simple taste masking by
means of
high flavor levels cannot offset undesirable effects encountered at high
levels of
inorganic divalent cations.
CA 03198533 2023- 5- 11
