CN116419682A - Nicotine pouch compositions - Google Patents

Nicotine pouch compositions Download PDF

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Publication number
CN116419682A
CN116419682A CN202180075476.XA CN202180075476A CN116419682A CN 116419682 A CN116419682 A CN 116419682A CN 202180075476 A CN202180075476 A CN 202180075476A CN 116419682 A CN116419682 A CN 116419682A
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China
Prior art keywords
nicotine
composition
pouch composition
pouch
weight
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Pending
Application number
CN202180075476.XA
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Chinese (zh)
Inventor
肯特·阿尔滨·尼尔森
杰西·波尔森
美·理·劳·斯塔尔
哈雷·拜恩·雅各布森
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Philip Morris Products SA
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Philip Morris Products SA
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Publication date
Priority claimed from US17/099,446 external-priority patent/US20220151292A1/en
Priority claimed from EP20207822.6A external-priority patent/EP4000424B1/en
Application filed by Philip Morris Products SA filed Critical Philip Morris Products SA
Publication of CN116419682A publication Critical patent/CN116419682A/en
Pending legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/10—Chemical features of tobacco products or tobacco substitutes
    • A24B15/16—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B13/00—Tobacco for pipes, for cigars, e.g. cigar inserts, or for cigarettes; Chewing tobacco; Snuff
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/18—Treatment of tobacco products or tobacco substitutes
    • A24B15/28—Treatment of tobacco products or tobacco substitutes by chemical substances
    • A24B15/42—Treatment of tobacco products or tobacco substitutes by chemical substances by organic and inorganic substances

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Toxicology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Manufacture Of Tobacco Products (AREA)

Abstract

A pouch composition is disclosed comprising a nicotine-ion exchange resin combination, water in an amount of at least 15% by weight of the pouch composition, and an inorganic divalent cation. In addition, an oral pouch nicotine product comprising a saliva-permeable pouch and a pouch composition in the pouch and a pouch composition are disclosed.

Description

Nicotine pouch compositions
Technical Field
The present invention relates to a pouch composition and an oral pouch nicotine product according to the claims.
Background
Delivery of nicotine by smoking has many well known drawbacks, particularly health related problems, such as the introduction of carcinogens.
However, tobacco substitutes also suffer from drawbacks such as inadequate relief from craving for the user.
Another challenge in the prior art is that the desired release of nicotine should be attractive to the user of the pouch from the point of view of the user.
Yet another challenge associated with the prior art may be that the pouch as a delivery vehicle for nicotine may be somewhat expensive and thus places restrictions on the design of the pouch in order to control manufacturing costs.
It is an object of an embodiment of the present invention to provide a nicotine-containing pouch, e.g. as a tobacco substitute, which solves the above-mentioned problems.
Disclosure of Invention
The present invention relates to a pouch composition comprising
A nicotine-ion exchange resin combination, wherein,
water in an amount of at least 15% by weight of the pouch composition, and
inorganic divalent cations.
An advantage of the present invention may be that a relatively high stability of the provided nicotine may be obtained while a relatively fast release of nicotine is obtained. Achieving high stability may result in nicotine being too effectively e.g. bound to the carrier and thus slow release. By means of the claimed pouch composition comprising water in an amount of at least 15% by weight of the composition in combination with divalent inorganic cations, a high stability is facilitated but still a fast release is achieved, while also having a very desirable mouthfeel and taste. The high water content contributes to an efficient release of nicotine during use.
An advantage of the present invention is that a relatively fast release rate of nicotine from the pouch composition can be obtained due to the presence of divalent cations. At the same time, the desired moist mouthfeel is provided due to the high water content, which also promotes rapid nicotine release.
Furthermore, the present invention may advantageously provide more efficient nicotine release during use of the pouch comprising the pouch composition. Due to the minimization of any residual nicotine not released from the pouch composition, obtaining an effective release of nicotine may result in a lower total dose of nicotine and the same amount of nicotine released.
In an advantageous embodiment of the invention, the solid oral nicotine formulation comprises inorganic divalent cations in a molar ratio of at least 0.1, such as at least 0.25, 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 a 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.
The amount of divalent cations should advantageously be high enough to enable ion exchange of the complexed nicotine with the divalent cations during use of the pouch comprising the pouch composition.
Furthermore, the amount of inorganic divalent cations can also advantageously reduce the probability of the exchanged nicotine re-complexing with the ion exchange resin, simply by occupying binding sites on the ion exchange resin during use.
In one embodiment of the invention, the amount of inorganic divalent cations may even prevent re-complexation of nicotine exchanged during use with the ion exchange resin.
In addition, the amount of inorganic divalent cations can reduce the probability of complexing/re-complexing any uncomplexed nicotine, such as free base nicotine, and/or exchanged nicotine 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 with respect to the amount of nicotine in the nicotine-ion exchange resin combination, such as at most 3.75 with respect to the amount of nicotine in the nicotine-ion exchange resin combination, such as at most 2.5 with respect to the amount of nicotine in the nicotine-ion exchange resin combination.
One advantage of the above embodiments may be that the inclusion of inorganic divalent cations in a not too high amount will promote the desired taste and mouthfeel by avoiding or minimizing undesirable tastes and/or mouthfeel such as undesirable salty taste, localized dehydration, or even a mouth dehydration sensation.
In one embodiment of the invention, the pouch composition comprises an inorganic divalent cation 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 between 0.1 and 6.0 relative to the amount of nicotine in the nicotine-ion exchange resin combination, such as between 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.
In one embodiment of the invention, the pouch composition comprises the inorganic divalent cation 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 one embodiment of the invention, the pouch composition comprises the inorganic divalent cation in a molar ratio of between 0.01 and 5.0 relative to the amount of 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 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 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 divalent cations of calcium and magnesium.
In one embodiment of the invention, the inorganic divalent cation is provided as a salt comprising an inorganic or organic anion.
In an advantageous embodiment of the invention, the inorganic divalent cation is provided as a salt comprising an anion selected from the group consisting of: carboxylate, such as acetate, lactate, oxalate, propionate or levulinate; an organic sulfonate group; organic sulfate radicals; an organic phosphate group; chloride, bromide, nitrate, sulfate, hydrogen phosphate, oxygen ions, and any combination thereof.
In one embodiment of the invention, the inorganic divalent cation is provided as a salt in an amount of between 0.1 and 15.0 wt% of the composition, such as between 0.1 and 10.0 wt% of the composition, such as between 0.5 and 10.0 wt% of the composition.
In one embodiment of the invention, the organic anion is selected from carboxylates, such as acetate, lactate, oxalate, propionate, levulinate; an organic sulfonate group; organic sulfate radicals; an organic phosphate group; and any combination thereof.
In an advantageous embodiment of the invention, the inorganic divalent cations are provided as inorganic salts.
In an advantageous embodiment of the invention, the inorganic divalent cation is provided as inorganic salt in an amount of between 0.1 and 15.0 wt.% of the composition, such as between 0.1 and 10.0 wt.% of the composition, such as between 0.5 and 10.0 wt.% of the composition.
In one embodiment of the invention, the inorganic divalent cation is provided as an inorganic salt in an amount of between 0.1 and 15.0 wt% of the composition, such as between 0.1 and 10.0 wt% of the composition, such as between 0.5 and 10.0 wt% of the composition.
In one embodiment of the invention, the inorganic divalent cation is provided as an inorganic salt in an amount of between 0.1 and 15.0 wt% of the composition, such as between 0.1 and 10.0 wt% of the composition, such as between 0.5 and 7.0 wt% of the composition, such as between 0.1 and 7.0 wt% of the composition, such as between 0.5 and 5.0 wt% of the composition, such as between 0.5 and 4.0 wt% of the composition.
In an advantageous embodiment of the invention, the inorganic divalent cation is provided as an inorganic salt comprising an inorganic anion selected from the group consisting of: chloride, bromide, nitrate, sulfate, bicarbonate, hydrogen phosphate, oxygen, hydroxide, and any combination thereof.
It should be noted that in some embodiments, the inorganic anions may be combined, for example, such that the cation forms a separate salt with two different types of anions. An example may be, for example, magnesium chloride in combination with magnesium bromide.
In an advantageous embodiment of the invention, wherein the inorganic divalent cation is provided as an inorganic salt comprising an inorganic anion selected from the group consisting of: chloride, bromide, sulfate, bicarbonate, and any combination thereof.
In an advantageous embodiment of the invention, wherein the inorganic divalent cation is provided as an inorganic salt comprising an inorganic anion selected from the group consisting of: chloride, bromide, sulfate, and any combination thereof.
In an advantageous embodiment of the invention, wherein the inorganic divalent cation is provided as an inorganic salt comprising an inorganic anion selected from the group consisting of: chloride, bromide, and any combination thereof.
In an advantageous embodiment of the invention, the inorganic anions comprise chloride ions.
In one embodiment of the invention, the inorganic cation is magnesium and/or calcium and the anion comprises chloride.
In one embodiment of the invention, the inorganic anion is chloride.
In one embodiment of the invention, the inorganic cation is magnesium and/or calcium and the anion is chloride.
In an advantageous embodiment of the invention, the inorganic divalent cation is provided as an inorganic salt selected from calcium chloride or magnesium chloride or a combination thereof.
In one embodiment of the invention, the divalent cation is provided as a pharmaceutically acceptable salt.
In one embodiment of the invention, the divalent cation is provided as a pharmaceutically acceptable inorganic salt.
In one embodiment of the invention, the inorganic divalent cation is provided as a hydrated salt.
In one embodiment of the invention, the inorganic divalent cation is provided as a hydrated inorganic salt.
In one embodiment of the invention, the divalent cation is provided as an acceptable salt for the digestive tract.
In one embodiment of the invention, the divalent cation is provided as an inorganic salt acceptable to the digestive tract.
In an advantageous embodiment of the invention, the divalent cation is provided as a water soluble salt having a water solubility of at least 5 grams per 100mL of water measured at 25 degrees celsius, atmospheric pressure, and pH 7.0.
Atmospheric pressure is understood to be a pressure of about 101.3kPa or a pressure in the range of 90 to 110 kPa.
In one embodiment of the invention, the pouch composition comprises an inorganic divalent cation provided as a water-soluble salt, wherein the pouch composition comprises the inorganic divalent cation 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 between 0.1 and 6.0 relative to the amount of nicotine in the nicotine-ion exchange resin combination, such as between 0.1 and 5.0 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 one embodiment of the invention, the inorganic divalent cation is provided as a water soluble salt in an amount between 0.1 and 15.0% by weight of the composition.
In one embodiment of the invention, the divalent cation is provided as an inorganic, water-soluble salt having a water solubility of at least 5 grams per 100mL of water measured at 25 degrees celsius, atmospheric pressure, and pH 7.0.
In one embodiment of the invention, the inorganic divalent cation is provided as a water soluble salt in an amount of between 0.1 and 15.0 wt% of the composition, such as between 0.1 and 10.0 wt% of the composition, such as between 0.5 and 7.0 wt% of the composition, such as between 0.1 and 7.0 wt% of the composition, such as between 0.5 and 5.0 wt% of the composition, such as between 0.5 and 4.0 wt% of the composition.
In one embodiment of the invention, the pouch composition comprises an inorganic divalent cation provided as an inorganic water-soluble salt, wherein the pouch composition comprises the inorganic divalent cation 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 between 0.1 and 6.0 relative to the amount of nicotine in the nicotine-ion exchange resin combination, such as between 0.1 and 5.0 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 one embodiment of the invention, the inorganic divalent cation is provided as an inorganic, water-soluble salt in an amount of between 0.1 and 15.0 wt% of the composition, such as between 0.1 and 10.0 wt% of the composition, such as between 0.5 and 7.0 wt% of the composition, such as between 0.1 and 7.0 wt% of the composition, such as between 0.5 and 5.0 wt% of the composition, such as between 0.5 and 4.0 wt% of the composition.
"providing" is herein understood to mean that the inorganic cation is added to the composition as a salt.
By providing divalent cations as water-soluble salts, the dissociation of the salts into cations can advantageously be faster and more efficient, whereby relatively fast nicotine release can be achieved.
In an advantageous embodiment of the invention, the pouch composition comprises nicotine in an amount of at least 0.1% by weight of the pouch composition, such as at least 0.2% by weight.
In one 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.
The pouch composition should have a desired content of nicotine that is capable of providing a desired dose of nicotine to the user while also providing a desired volume of the composition enclosed in the pouch to the user.
In an advantageous embodiment of the invention, the pouch composition comprises a nicotine-ion exchange combination in an amount of 0.1 to 20% by weight of the pouch composition.
It is understood herein that the divalent cations do not form part of the nicotine-ion exchange combination when the pouch composition is prepared. If combined prior to preparing the pouch composition. Pre-combination may cause stability problems because divalent cations may induce premature release of nicotine from the ion exchange resin. This can be particularly problematic when such a combination is incorporated into a pouch composition having a high water content, such as having a water content of at least 15% by weight of the pouch composition.
In one embodiment of the invention, divalent cations are not included in the provided nicotine-ion exchange combinations.
In one embodiment of the invention, the nicotine-ion exchange combination does not comprise divalent cations.
In one embodiment of the invention, the divalent cation is provided as a salt.
In one embodiment of the invention, the pouch composition comprises a 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 one embodiment of the invention, the pouch composition comprises a 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 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 one embodiment of the invention, the nicotine-ion exchange resin combination comprises nicotine complexed with an ion exchange resin, wherein the nicotine comprises an amount between 5 and 50% by weight of the nicotine-ion exchange resin combination.
In one embodiment of the invention, the nicotine-ion exchange resin combination consists of nicotine complexed with an ion exchange resin, wherein nicotine constitutes an amount between 10 and 50% by weight of the nicotine-ion exchange resin combination, such as between 10 and 40% by weight of the nicotine-ion exchange resin combination, such as between 10 and 30% by weight of the nicotine-ion exchange resin combination, such as between 10 and 25% by weight of the nicotine-ion exchange resin combination.
In one embodiment of the invention, the nicotine-ion exchange resin combination comprises free base nicotine admixed with an ion exchange resin, wherein nicotine comprises an amount of between 5 and 50% by weight of the nicotine-ion exchange resin combination.
In one embodiment of the invention, the nicotine-ion exchange resin combination comprises free base nicotine admixed with an ion exchange resin, wherein nicotine constitutes an amount between 5 and 50% by weight of the nicotine-ion exchange resin combination, such as between 10 and 50% by weight of the nicotine-ion exchange resin combination, such as between 20 and 50% by weight of the nicotine-ion exchange resin combination, such as between 25 and 45% by weight of the nicotine-ion exchange resin combination.
In one embodiment of the invention, the nicotine-ion exchange resin combination comprises free base nicotine admixed with an ion exchange resin, wherein nicotine constitutes an amount between 5 and 40% by weight of the nicotine-ion exchange resin combination, such as between 10 and 35% by weight of the nicotine-ion exchange resin combination, such as between 10 and 25% by weight of the nicotine-ion exchange resin combination, such as between 10 and 15% by weight of the nicotine-ion exchange resin combination.
In an advantageous embodiment of the invention, the nicotine-ion exchange resin combination comprises between 5 and 50% by weight of nicotine and between 10 and 95% by weight of ion exchange resin.
In one embodiment of the invention, the nicotine-ion exchange resin combination comprises between 5 and 50% by weight nicotine and between 10 and 95% by weight ion exchange resin.
In one embodiment of the invention, the nicotine-ion exchange resin combination comprises between 10 and 30% by weight nicotine and between 20 and 90% by weight ion exchange resin.
In one embodiment of the invention, the nicotine-ion exchange resin combination consists of nicotine in an amount between 10 and 30% by weight and ion exchange resin in an amount between 70 and 90% by weight.
In one embodiment of the invention, the nicotine-ion exchange resin combination is substantially free of water.
In one embodiment of the invention, the nicotine-ion exchange resin combination further comprises a C3 sugar alcohol.
In one embodiment, the C3 sugar alcohol may be selected from glycerol, propylene glycol, and any combination thereof.
In one embodiment of the invention, the nicotine-ion exchange resin combination further comprises glycerin.
In one embodiment of the invention, the nicotine-ion exchange resin combination further comprises glycerin 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 one embodiment of the invention, the nicotine-ion exchange resin combination comprises between 5 and 50% by weight nicotine and between 20 and 75% by weight ion exchange resin.
In one embodiment of the invention, the nicotine-ion exchange resin combination comprises water in an amount of no more than 75 wt%, such as no more than 50 wt%, such as no more than 40 wt%, such as no more than 30 wt%, such as no more than 20 wt%, such as no more than 10 wt%, such as no more than 5 wt%.
In an advantageous embodiment of the invention, the ion exchange resin comprises one or more resins selected from the group consisting of:
(i) Methacrylic weak acid type resin containing carboxylic acid type functional group,
(ii) A copolymer of methacrylic acid and divinylbenzene, said copolymer containing carboxylic acid-based functional groups,
(iii) A strongly acidic type of polystyrene resin containing sulfonic acid-based functional groups,
(iv) A resin of medium acidic type in polystyrene containing phosphoric acid-based functional groups, and
(v) A combination thereof.
In an advantageous embodiment of the invention, the ion exchange resin comprises a polacrilex (polacrilex) resin.
In an advantageous embodiment of the invention, the ion exchange resin is a polyclelin resin.
In one embodiment of the invention, the ion exchange resin is a polyclelin resin.
In one embodiment of the invention, the polycottene resin comprises or is
Figure BDA0004217777500000081
In an advantageous embodiment of the invention, the nicotine-ion exchange resin combination comprises nicotine complexed with an ion exchange resin.
In an advantageous embodiment of the invention, the nicotine-ion exchange resin combination is nicotine complexed with an ion exchange resin.
Thus, in the above embodiments, the nicotine-ion exchange resin combination consists of nicotine complexed with an ion exchange resin.
In an advantageous embodiment of the invention, the nicotine-ion exchange resin combination comprises free base nicotine mixed with an ion exchange resin.
One advantage of the above embodiments may be to provide sustained release of nicotine. At the same time, the release rate of nicotine is not too slow to give the desired craving relief to the user.
In one embodiment of the invention, the nicotine-ion exchange resin combination is free base nicotine mixed with an ion exchange resin.
In one embodiment of the invention, the pouch composition further comprises nicotine.
In one embodiment of the invention, the pouch composition further comprises nicotine.
In one embodiment of the invention, the pouch composition further comprises nicotine selected from the group consisting of: nicotine salts, nicotine free base, nicotine bound to an ion exchanger such as an ion exchange resin (e.g. nicotine polyclelin resin), nicotine inclusion complex or any non-covalently bound nicotine; nicotine bound to zeolite; nicotine combined with 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 20-40% by weight of the composition, such as 25-35% by weight of the composition.
In one embodiment of the invention, the pouch composition comprises water in an amount of 15 to 65% by weight of the composition, such as 20 to 65% by weight of the composition, such as 25 to 65% by weight of the composition.
In one 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 one 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 composition, such as 15-40% by weight of the composition, such as 15-30% by weight of the composition.
In one 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 partially mixed into other components such as the fibers. For example, when nicotine ion exchange resin is added in combination with a mixture of free base nicotine and ion exchange resin and water, a significant amount of water in the final pouch composition can come from the mixture. For example, if the final amount of the pouch composition contains 5% water from the nicotine-ion exchange resin combination, up to one third of the water source in the pouch composition is from the nicotine-ion exchange resin combination.
In an advantageous embodiment of the invention, the pouch composition comprises at least one sugar alcohol.
In one embodiment of the present invention xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol and mixtures thereof are used as the at least one sugar alcohol. The at least one sugar alcohol may further comprise an additional sugar alcohol. As an example embodiment, hydrogenated starch hydrolysates may be used, comprising mixtures of sorbitol, maltitol and other sugar alcohols.
The sugar alcohol may advantageously promote and induce salivation of the pouch composition, thereby achieving dissociation of the inorganic divalent cations and release of nicotine, 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 nicotine release from the pouch.
In addition, sugar alcohols can be advantageously used to obtain a desired mouthfeel by increasing salivary secretion and thereby counteract any localized dehydration or mouth dehydration sensation experienced by the pouch user.
Thus, sugar alcohols can be advantageously used in combination with inorganic divalent cations to achieve the desired nicotine release while also achieving the desired taste.
In one 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 should be noted that different sugar alcohols may be applied for taste and salivation purposes, wherein the sugar alcohol composition is made of different sugar alcohols having different properties in terms of storage, bacterial growth, processability and/or taste.
In one 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.
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 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 one embodiment, 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 one embodiment, 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 50% by weight of the composition.
In an advantageous embodiment of the invention, the pouch composition comprises at least one water insoluble fiber.
In an advantageous embodiment of the invention, the bag composition comprises said water insoluble fiber in an amount of between 5 and 50% by weight of the bag composition, such as 10-45% by weight of the bag composition, such as 15-40% by weight of the bag composition.
In one embodiment of the invention, the pouch composition comprises said water insoluble fiber in an amount of between 5 to 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.
In one embodiment of the invention, the pouch composition comprises said water insoluble fiber in an amount of between 5 to 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.
One advantage of the above embodiments may be that residues remain even after use of the nicotine pouch comprising the pouch composition. This may give the user of the nicotine bag a pleasant perception, for example due to the similarity to tobacco-containing products.
The water insoluble fiber may advantageously provide a desired mouthfeel throughout the use of the bag.
In an advantageous embodiment of the invention, the water-insoluble fiber is a vegetable fiber.
In an advantageous embodiment of the invention, the water insoluble fiber is selected from the group consisting of wheat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, cellulose fiber, bran fiber, bamboo fiber, powdered cellulose and combinations thereof.
Powdered cellulose within the scope of the present invention is understood to be cellulose produced by processing alpha-cellulose obtained as pulp, such as wood pulp, from a fibrous plant material line.
In one embodiment of the invention, the water insoluble fiber comprises or consists of cereal plant fibers.
In one embodiment of the invention, the water insoluble fiber comprises or consists of fruit and/or vegetable fibers.
In one embodiment of the invention, the water-insoluble composition comprises or consists of water-insoluble fibers selected from the group consisting of: wheat fiber, oat fiber, pea fiber, powdered cellulose, or combinations thereof.
In one embodiment of the invention, the water insoluble fiber is selected from wheat fiber, oat fiber, pea fiber, powdered cellulose or a combination thereof.
In one embodiment of the invention, the water-insoluble composition comprises or consists of water-insoluble fibers selected from the group consisting of: wheat fiber, oat fiber, pea fiber, or combinations thereof.
In one embodiment of the invention, the water insoluble fiber is selected from wheat fiber, oat fiber, pea fiber, or a combination thereof.
In one embodiment of the invention, the water-insoluble composition comprises or consists of water-insoluble fibers selected from the group consisting of: wheat fiber, oat fiber, or combinations thereof.
In one embodiment of the invention, the water insoluble fiber is selected from wheat fiber, oat fiber, or a combination thereof.
In one embodiment of the invention, the water insoluble fiber is powdered cellulose.
Non-limiting examples of useful water insoluble fibers include Vitacel WF 600, vitacel HF 600, vitacel P95, vitacel WF 200, vitacel L00, vitacel Erbsenfaser EF 150, vitacel bamboo fiberbaf, vitacel HF 600, vitacel Cellulose L G, vitacel PF200, vitacel potatofiber KF200, vitacel bamboo fiberhaf BAF40, vitacel Haferfaser/oat fiber HF-401-30US.
Non-limiting examples of powdered cellulose that may be used include Vitacel L00, vitacel Cellulose L G, vitacel LC1000, vitacel L600-20, vitacel L600, and the like.
In one embodiment, the powdered cellulose is not chemically modified. Thus, the powdered cellulose may be cellulose fibers that have not been chemically modified, which do not include, for example, 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%.
One advantage of the above embodiments may be the high water binding capacity enabling a bag composition with a high water content.
Furthermore, bags with high water content were found to have desirable texture and mouthfeel while still being able to store the manufactured bags together adjacent, e.g. in cans or the like without adhering together too much resulting in breakage of the bag upon removal.
In addition, the water insoluble fiber having a high water binding capacity may reduce any nicotine exchange caused by divalent cations that occurs before the pouch is used.
Thus, a pouch comprising water-insoluble fibers having a high water binding capacity may advantageously have a reduced Relative Standard Deviation (RSD) of nicotine content.
In an advantageous embodiment of the invention, the nicotine content between a series of at least 10 oral bags comprising said bag composition is kept below 10%, preferably below 8%, more preferably at most 6%, even more preferably at most 4%, most preferably at most 2% Relative Standard Deviation (RSD).
In one embodiment of the invention the nicotine content between a series of at least 10 oral bags comprising said bag composition is maintained at a Relative Standard Deviation (RSD) of 0.1-10%, preferably 0.1-8%, more preferably 0.1-6%, even more preferably 0.1-4%, most preferably 0.1-2%.
In one embodiment of the invention, the water insoluble fiber has a water binding capacity of 300 to 1500%, such as 400 to 1300%.
In one 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 one 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 one 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 1200%, such as 500 to 1000%.
In one embodiment of the invention, the water insoluble fiber has a swelling capacity of at least 5.0mL/g, such as 5.0-20 mL/g.
One advantage of the above embodiments is that the amount of water insoluble fiber can be reduced without compromising mouthfeel during use. If a certain amount of water-insoluble fiber is substituted for the water-soluble component, the swelling of the water-insoluble fiber will counteract the dissolution of the water-soluble component during use, and thus the user will not experience any reduction of the bag content during use.
In one embodiment of the invention, the water insoluble fiber is selected from pea fibers, powdered cellulose, and combinations thereof, and wherein the pouch composition comprises a flavoring in an amount of no more than 10% by weight of the pouch composition.
In one embodiment of the invention, the pouch composition comprises water insoluble fiber selected from pea fiber and powdered cellulose or combinations thereof in an amount of 0.01-10% by weight of the pouch composition of the flavoring agent.
In an advantageous embodiment of the invention, the water-insoluble fiber has a density of 50 to 500 g/l, such as 100 to 400 g/l, such as 200 to 300 g/l.
The use of water insoluble fibers having a relatively low bulk density will not only provide a good mouthfeel, but will also provide for an effective release from the pouch due to the fact that the relatively low bulk density promotes effective salivary secretion to dissolve and release the water soluble components of the composition.
In an advantageous embodiment of the invention, the pouch composition comprises a pH adjuster.
In an advantageous embodiment of the invention, the pouch composition comprises a pH adjusting agent in an amount of 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.
It may be desirable to obtain a relatively fast nicotine release rate and an efficient uptake/absorption, as this will ensure a fast effect on the user, i.e. craving relief.
Furthermore, having a combination of efficient release and efficient absorption advantageously enables relatively high utilization of the nicotine dose within the pouch. The relatively high utilization of the nicotine dose within the pouch may further provide for a reduction of the necessary nicotine dose of the pouch without compromising the resulting effect. Lower nicotine doses in turn can lead to reduced production costs, as nicotine can be relatively expensive, but can also assist users desiring to reduce their nicotine intake.
In an advantageous embodiment of the invention, the pH adjustor is an alkaline pH adjustor, such as an alkaline buffer.
In an advantageous embodiment of the invention, the pH adjusting agent is a buffer, such as an alkaline buffer.
In one embodiment of the invention, the pH adjuster is water soluble.
In one embodiment of the invention, the pH adjustor has a water solubility of at least 5 grams per 100mL of water measured at 25 degrees Celsius, atmospheric pressure, and pH 7.0.
In one embodiment of the invention, the pouch composition is adapted to give a pH of at least 8.0, such as a pH of at least 9.0, when 2.0 grams of the pouch composition is added to 20ml of 0.02m potassium dihydrogen phosphate buffer (pH adjusted to 7.4).
One advantage of the above embodiments may be that relatively efficient nicotine uptake is facilitated due to the high pH values obtained.
Another advantage of the above embodiments may be that the need for preservatives may be reduced or even eliminated, and low amounts of such preservatives may be used if not absent.
In addition, the high pH values obtained may advantageously provide a tingling sensation in the mouth that may be perceived as a desired mouthfeel, for example due to similarity to tobacco-based pouch products.
In one embodiment of the invention, the pH adjusting agent is selected from acetic acid, adipic acid, citric acid, fumaric acid, glucono-delta-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, potassium carbonate, calcium carbonate, magnesium oxide, or any combination thereof.
In one embodiment of the invention, the pH adjusting agent is selected from acetic acid, adipic acid, citric acid, fumaric acid, glucono-delta-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 oxide, or any combination thereof.
In an advantageous embodiment of the invention, the pH adjusting agent is selected from sodium carbonate, sodium bicarbonate, potassium carbonate and magnesium carbonate; potassium bicarbonate; tromethamine; phosphate buffer, amino acid, or any combination thereof.
In one embodiment, the pouch composition comprises an inorganic divalent cation, which may be provided as a water soluble salt, and in addition thereto comprises a pH adjusting agent selected from the group consisting of: sodium carbonate, sodium bicarbonate, potassium carbonate, and magnesium carbonate; potassium bicarbonate; tromethamine; phosphate buffer; amino acids, or any combination thereof.
In one embodiment, the pouch composition comprises an inorganic divalent cation, which may be provided as a water soluble salt, and in addition thereto comprises a pH adjusting agent selected from the group consisting of: sodium carbonate, sodium bicarbonate, potassium carbonate, and magnesium carbonate; potassium bicarbonate; tromethamine; phosphate buffer; or any combination thereof.
In one embodiment, the pouch composition comprises an inorganic divalent cation, which may be provided as a water soluble salt, and in addition thereto comprises a pH adjusting agent selected from the group consisting of: sodium carbonate, sodium bicarbonate, potassium carbonate, and magnesium carbonate; potassium bicarbonate; tromethamine; or any combination thereof.
In this context, the term "tromethamine" refers to (tris (hydroxymethyl) aminomethane), sometimes also referred to as tris buffer.
In the present context, the term "phosphate buffer" refers to alkali metal and alkaline earth metal phosphates such as sodium orthophosphate, potassium orthophosphate, calcium orthophosphate, sodium diphosphate, 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 tromethamine, amino acid and phosphate buffer or any combination thereof.
In an advantageous embodiment of the invention, the pH adjusting agent is selected from tromethamine and phosphate buffer or any combination thereof.
Tromethamine and phosphate buffers have desirable relatively neutral tastes and therefore the use of these pH adjusters may not impair the taste and mouthfeel of the pouch composition.
In an advantageous embodiment of the invention, the pH regulator is selected from tromethamine.
In one embodiment of the invention, the pH adjuster is tromethamine.
In one embodiment of the invention, the pH adjuster comprises tromethamine.
In one embodiment of the invention, the pH adjusting agent is an amino acid.
In one embodiment of the invention, the pH adjuster comprises an amino acid.
In one embodiment of the invention, the pH adjustor is a phosphate buffer.
In one embodiment of the invention, the pH adjuster comprises a phosphate buffer.
In one embodiment of the invention, the pH adjustor is a 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 one embodiment, the pH adjuster is an alkali metal phosphate buffer.
In one embodiment, the phosphate buffer is an alkali metal phosphate buffer.
In one embodiment, the phosphate buffer is an alkali metal phosphate buffer selected from the group consisting of: sodium orthophosphate, potassium orthophosphate, sodium diphosphate, potassium diphosphate, pentasodium triphosphate, pentapotassium triphosphate, sodium polyphosphate, potassium polyphosphate, and combinations thereof.
In one embodiment, the phosphate buffer is provided as a water-soluble composition.
In one embodiment of the invention, the pH adjuster does not comprise carbonate and/or bicarbonate.
In one embodiment of the invention, the pH adjustor is a non-carbonate and/or non-bicarbonate buffer or a combination thereof.
In one embodiment of the invention, the pouch composition is free of carbonates.
In one embodiment of the invention, the pouch composition comprises a humectant.
In one embodiment, the wetting agent is selected from the following list: glycerol, propylene glycol, alginate, pectin, modified starch, hydroxypropyl cellulose, glyceryl triacetate, polyethylene glycol (PEG), xanthan gum, and combinations thereof.
In one embodiment, the humectant is or comprises the humectant in an amount of from 0.5 to 10%, such as from 0.5 to 5% by weight of the pouch composition, such as 1-3% by weight of the pouch composition.
In one embodiment, the humectant is or comprises an alginate, such as sodium alginate, for example, 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 one embodiment of the invention, the pouch composition is free of alginate.
In one embodiment of the invention, the pouch composition is free of humectants consisting of alginate, pectin, and xanthan gum.
In one embodiment of the invention, the pouch composition is free of humectants selected from the list: glycerol, propylene glycol, alginate, pectin, modified starch, hydroxypropyl cellulose, glyceryl triacetate, polyethylene glycol (PEG), xanthan gum, and combinations thereof.
In one 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% of nicotine within 10 minutes upon exposure to the 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 than a corresponding pouch composition without divalent cations upon exposure 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 composition, such as 0.05-1.0% 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 wt.%, as a flavour enhancer. The addition of higher amounts of sodium chloride may cause undesirable taste or mouthfeel.
In an advantageous embodiment of the invention, the pouch composition further comprises a preservative.
The preservative may help to keep the pouch composition from undesirable microbial growth.
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 useful preservatives within the scope of the present invention include 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 preservative, such as less than 0.05% by weight of preservative.
Thus, the pouch composition may comprise a preservative in an amount of 0 to 0.1% by weight, such as in an amount of 0 to 0.05% by weight. This includes zero preservative content, i.e., the pouch composition is preservative-free. By obtaining a relatively alkaline environment, in particular by using the free base nicotine, a low or even no preservative use can be achieved.
In an advantageous embodiment of the invention, the pouch composition is preservative-free.
In an advantageous embodiment of the invention, the pouch composition is a non-tobacco pouch composition.
In an advantageous embodiment of the invention, the pouch composition comprises less than 2.0% 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 non-tobacco fibers.
In an advantageous embodiment of the invention, the pouch composition is a powdered composition.
The invention also relates to an oral pouch nicotine product comprising a saliva permeable pouch and a pouch composition according to the invention or any embodiment thereof enclosed in said pouch.
In an advantageous embodiment of the invention, the packaged nicotine product comprises nicotine in an amount of 0.5 to 20mg, such as 1.0 to 20mg, such as 5.0 to 15 mg.
In an advantageous embodiment of the invention, the packaged nicotine product comprises nicotine-ion exchange combinations in an amount of 1 to 100mg per bag.
In one embodiment of the invention, the packaged nicotine product comprises a nicotine-ion exchange combination in an amount of 1 to 100mg per bag, such as 10 to 90mg per bag, such as 10 to 80mg per bag, such as 20 to 80mg per bag, such as 30 to 80mg per bag, such as 40 to 80mg per bag, such as 50 to 80mg per bag.
In one embodiment of the invention, the packaged nicotine product comprises a nicotine-ion exchange combination in an amount of 1 to 100mg per bag, such as 10 to 80mg per bag, such as 10 to 60mg per bag, such as 20 to 50mg per bag.
In one embodiment of the invention, the divalent cation is provided as a salt having a water solubility of 5-500 grams per 100mL of water measured at 25 degrees celsius, atmospheric pressure, and pH 7.0, such as 5-350 grams per 100mL of water measured at 25 degrees celsius, atmospheric pressure, and pH 7.0.
In one embodiment of the invention, the inorganic divalent cation is provided as a salt in an amount of between 0.1 and 15.0 wt% of the composition, such as between 0.1 and 10.0 wt% of the composition, such as between 0.5 and 10.0 wt% of the composition, and the inorganic divalent cation is provided as an inorganic salt comprising an inorganic anion selected from the group consisting of chloride, bromide, bicarbonate, sulfate, and any combination thereof.
In one embodiment of the invention, the inorganic divalent cation is 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 cation is provided as a water soluble salt having a water solubility of at least 5 grams per 100mL of water measured at 25 degrees celsius, atmospheric pressure, and pH 7.0.
In one embodiment of the invention, the inorganic divalent cation is provided as an inorganic salt in an amount of between 0.1 and 15.0 wt% of the composition, such as between 0.1 and 10.0 wt% of the composition, such as between 0.5 and 10.0 wt% of the composition, and the water soluble salt has a water solubility of at least 5 grams per 100mL of water measured at 25 degrees celsius, atmospheric pressure, and pH 7.0.
In one embodiment of the invention, the inorganic divalent cation is 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 amount of at least 0.1% by weight of the pouch composition, such as at least 0.2% by weight.
In one embodiment of the invention, the inorganic divalent cation is 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 at least 0.2% by weight, of the pouch composition, and the solid oral nicotine formulation comprises the inorganic divalent cation 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 one embodiment of the invention, the inorganic divalent cation is 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 comprising nicotine in an amount of at least 0.1% by weight, such as at least 0.2% by weight, of the pouch composition, and the pouch composition comprises the inorganic divalent cation in a molar ratio of at most 6.5 with respect to the amount of nicotine in the nicotine-ion exchange resin combination, such as at most 6.0 with respect to the amount of nicotine in the nicotine-ion exchange resin combination, such as at most 5 with respect to the amount of nicotine in the nicotine-ion exchange resin combination, such as at most 3.75 with respect to the amount of nicotine in the nicotine-ion exchange resin combination, such as at most 2.5.
In one embodiment of the invention, the inorganic divalent cation is 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 a nicotine-ion exchange combination in an amount of between 0.1 and 20% by weight of the pouch composition.
In one embodiment of the invention, the inorganic divalent cation is 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 a 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 the inorganic divalent cation 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 one embodiment of the invention, the inorganic divalent cation is 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 a nicotine-ion exchange combination in an amount of 0.1 to 20% by weight of the pouch composition, and the pouch composition comprises the inorganic divalent cation 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 one embodiment of the invention, the nicotine-ion exchange resin combination comprises between 5 and 50% by weight nicotine and between 10 and 95% by weight ion exchange resin, and the ion exchange resin is a polycleirine resin.
In one embodiment of the invention, the pouch composition comprises a 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 an ion exchange resin in an amount of between 10 and 95% by weight, and the ion exchange resin is a polyclelin resin.
In one embodiment of the invention, the inorganic divalent cation is 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 a nicotine-ion exchange combination in an amount of between 0.1 and 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 of the composition, such as 20-40% by weight of the composition.
In one embodiment, 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 one embodiment of the invention, the inorganic divalent cation is provided as a salt in an amount of between 0.1 and 15.0 wt% of the composition, such as between 0.1 and 10.0 wt% of the composition, such as between 0.5 and 10.0 wt% of the composition, the pouch composition comprises a nicotine-ion exchange combination in an amount of between 0.1 and 20 wt% of the pouch composition, the pouch composition comprises a sugar alcohol in an amount of 15-65 wt% of the composition, such as 15-60 wt% of the composition, such as 15-50 wt% of the composition, such as 20-40 wt% of the composition, and the pouch composition comprises a sugar alcohol in an amount of 1 to 80 wt% of the composition, such as 2 to 70 wt% of the composition, such as 5 to 60 wt% of the composition, such as 10 to 50 wt% of the composition, such as 15 to 50 wt% of the composition.
In one 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 water insoluble fiber in an amount of between 5 to 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 one 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, the pouch composition comprises said water insoluble fiber in an amount of between 5 to 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 20-40% by weight of the composition.
In one embodiment of the invention, the bag composition comprises said water insoluble fiber in an amount of 5 to 50% by weight of the bag composition, such as 10-45% by weight of the bag composition, such as 15-40% by weight of the bag composition, and said water insoluble fiber is selected from the group consisting of wheat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, cellulose fiber, bran fiber, bamboo fiber, powdered cellulose and combinations thereof.
In one embodiment of the invention, the inorganic divalent cation is provided as a salt in an amount of between 0.1 and 15.0 wt% of the composition, such as between 0.1 and 10.0 wt% of the composition, such as between 0.5 and 10.0 wt% of the composition, the pouch composition comprises a nicotine-ion exchange combination in an amount of between 0.1 and 20 wt% of the pouch composition, the pouch composition comprises water in an amount of between 15 and 65 wt% of the composition, such as between 15 and 60 wt% of the composition, such as between 15 and 50 wt% of the composition, such as between 20 and 40 wt% of the composition, the pouch composition comprises sugar alcohol in an amount of between 1 and 80 wt% of the composition, such as between 2 and 70 wt% of the composition, such as between 5 and 60 wt% of the composition, such as between 10 and 50 wt% of the composition, such as between 15 and 50 wt% of the pouch composition, and the pouch composition comprises water insoluble fiber in an amount of between 10 and 45 wt% of the pouch composition, such as between 15 and 40 wt% of the pouch composition.
In one embodiment of the invention, the pouch composition comprises a pH adjuster in an amount of 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 adjuster is selected from sodium carbonate, sodium bicarbonate, potassium carbonate and magnesium carbonate; potassium bicarbonate; tromethamine; phosphate buffer, or any combination thereof.
In one embodiment of the invention, the pouch composition comprises a pH adjuster selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, and magnesium carbonate in an amount of 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; potassium bicarbonate; tromethamine; phosphate buffer, or any combination thereof, and the divalent cation is provided as a water soluble salt having a water solubility of at least 5 grams per 100mL of water measured at 25 degrees celsius, atmospheric pressure, and pH 7.0.
In one embodiment of the invention, the pouch composition comprises a pH adjuster selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, and magnesium carbonate in an amount of 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; potassium bicarbonate; tromethamine; phosphate buffers, or any combination thereof, and the inorganic divalent cations are provided as inorganic salts comprising inorganic anions selected from chloride, bromide, bicarbonate, sulfate, and any combination thereof.
The present invention also relates to a pouch composition comprising
Nicotine-ion exchange resin combination, and
inorganic multivalent cations.
In an advantageous embodiment of the invention, the multivalent cations are selected from multivalent ions of calcium, magnesium, zinc, aluminum, barium, iron, manganese, copper, lead, cobalt, nickel, such as ca2+, mg2+, zn2+, al3+, ba2+, fe2+, fe3+, fe4+, mn2+, mn4+, cu4+, or any combination thereof.
In one embodiment of the invention, the multivalent cations are selected from ca2+, mg2+, zn2+, ba2+, fe2+, fe3+, fe4+, al3+, mn2+, mn4+, cu4+, and any combination thereof.
In an advantageous embodiment of the invention, the multivalent cations are selected from 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 cations.
In one embodiment, the trivalent cation is aluminum.
In one embodiment of the invention, the multivalent cation comprises aluminum chloride.
In one embodiment of the invention, the multivalent cations are selected from divalent cations of aluminum chloride, calcium, magnesium, iron, zinc, and any combination thereof.
In an advantageous embodiment of the invention, the multivalent cations are selected from divalent cations of calcium, magnesium, iron, zinc and any combination thereof.
In an advantageous embodiment of the invention, the multivalent cations are selected from divalent cations of calcium, magnesium and any combination thereof.
Detailed Description
As used herein, the term "pouch composition" refers to a composition for use in an oral pouch, i.e., a pouch for oral use. Thus, a pouch composition refers to a composition enclosed within a pouch. In addition, when referring to a composition enclosed within a pouch, the terms "pouch composition", "nicotine pouch composition" and "solid oral nicotine formulation" are used interchangeably.
As used herein, the term "nicotine" refers to nicotine used in the refined/separated substance. In particular, nicotine does not refer to tobacco material having a nicotine content. Thus, when referring to the amount of nicotine (also understood as the nicotine dose), this amount refers to the amount of pure nicotine.
Nicotine also encompasses nicotine that is not obtained from tobacco, commonly referred to as synthetic nicotine.
As used herein, "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 amounts of the first component and the second component may also be presented in terms of 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 present in a pouch comprising 0.1 equivalent of divalent cations relative to the amount of nicotine in the nicotine-ion exchange resin combination, i.e. a pouch comprising 0.1 equivalent of divalent cations and 1 equivalent of nicotine in the nicotine-ion exchange resin combination.
As used herein, the term "free base nicotine" refers to an aprotic form of nicotine and thus excludes nicotine salts or nicotine provided as a complex between nicotine and an ion exchange resin. However, the free base nicotine may be mixed with an amount of ion exchange resin or water soluble composition such as sugar alcohol or water soluble fiber. Although free base nicotine includes both free base nicotine extracted from tobacco and synthetically manufactured free base nicotine, free base nicotine is not provided in the form of tobacco or powdered tobacco. Typically, the free base nicotine is provided as a liquid.
As used herein, the term "bag" is intended to mean a container generally formed from a web of fibrous material that encloses a cavity. The pouch is a pouch designed for the administration of an active ingredient in the oral cavity and is therefore suitable for oral use, it is non-toxic and water insoluble. The fibrous material may, for example, be formed into a woven or nonwoven web or fabric. For example, the pouch may be sealed by bonding two respective webs or fabrics to each other along their edges to form a cavity for nicotine and a water insoluble composition. To release 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 may come into contact with the nicotine, whereby the nicotine is released from the oral pouch.
As used herein, the term "nicotine-ion exchange resin combination" refers to a combination comprising nicotine complexed with an ion exchange resin and/or free base nicotine mixed with an ion exchange resin.
As used herein, the term "nicotine complexed with an 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 should be noted that even though some embodiments comprise a combination of nicotine complexed with an ion exchange resin and nicotine in its free base form in admixture with an ion exchange resin, the term "free base nicotine in admixture with an ion exchange resin" requires the presence of nicotine in its free base form. In some embodiments, the mixture is an aqueous mixture. Mixing the free base nicotine and water with an ion exchange resin, thereby obtaining a mixture comprising both free base nicotine and ion exchange resin. The free base nicotine mixed with the ion exchange resin is referred to as a "premix" in the examples.
As used herein, the term "powder composition" refers to a composition in powder form, i.e., as a particulate material having a relatively small particle size, e.g., a particle size between 1 and 1200 microns. In particular, the powder composition does not mean powdered tobacco.
As used herein, the term "humectant" is understood to be a humectant used to keep the bag moist, i.e. a humectant is added to the bag composition for the purpose of keeping the bag moist. Thus, the term humectant does not refer to substances added for other purposes, hereinafter also hygroscopic substances added for other purposes, such as sugar alcohols, water insoluble fibers and glycerin associated with a nicotine-ion exchange resin combination such as the ion exchange resin in nicotine polacrilex. Examples of humectants include alginate, propylene glycol, hydroxypropyl cellulose, and glycerin. It should be noted that when glycerol is introduced as a humectant, the glycerol is added as free glycerol and is therefore liquid at room temperature. Further examples of humectants include glyceryl triacetate, modified starches, pectins, xanthan gum and the like. The term humectant does not refer to sugar alcohols containing 4 or more carbons. In addition, the term humectant does not refer to fibers such as water insoluble fibers, such as wheat fibers, pea fibers, rice fibers, corn fibers, oat fibers, tomato fibers, barley fibers, rye fibers, beet fibers, buckwheat fibers, potato fibers, cellulose fibers, apple fibers, cocoa fibers, cellulose fibers, bran fibers, bamboo fibers, powdered cellulose, and combinations thereof. In addition, the term wetting agent does not include, for example, naCl.
As used herein, the term "water-soluble" refers to relatively high water solubility, for example greater than 5 grams of a water-soluble composition or substance per 100mL of water measured at 25 degrees celsius, atmospheric pressure, and pH 7.0. Unless otherwise indicated, when referring to a "soluble" composition or substance, water-solubility is meant.
As used herein, the term "water insoluble" refers to relatively low water solubility, e.g., less than 0.1 gram of the composition or substance per 100mL of water measured at 25 degrees celsius, atmospheric pressure, and pH 7.0. In reference to "insoluble", unless otherwise indicated, means water insoluble. Thus, a composition or substance that has a water solubility of between 0.1 and 5 grams of the composition or substance per 100mL of water measured at 25 degrees celsius, atmospheric pressure, and pH 7.0 is neither considered water soluble nor water insoluble, but has an intermediate water solubility.
The pouch of the present invention provides nicotine release into the oral cavity. A nicotine release profile comprising both a fast release period and a sustained release period may be obtained.
As used herein, the term "rapid release" or "quick release period" may refer to the first 2 minutes of the nicotine release profile, while the term "sustained release period" refers to the period of time following the release profile until the end of the experiment or end of use.
As used herein, the term "rapid release rate" refers to the nicotine released per minute over the first 2 minutes.
As used herein, the term "effective release" refers to the total release of nicotine during the release or use period of an experiment.
As used herein, the term "dissolution" is a process in which a solid substance enters a solvent (such as oral saliva or water within a bag) to produce a solution.
Typically, the pouch comprises an opening, wherein the characteristic opening size is adapted to the characteristic size of the matrix composition, so as to retain the matrix composition within the pouch prior to use and/or to retain a portion of the matrix composition, such as a water insoluble composition, within the pouch during use.
In order to obtain a bag having a suitable opening size in view of the matrix composition to be used, the material of the bag may be chosen accordingly, including for example woven and/or nonwoven fabrics.
In other words, according to various embodiments, the pouch forms a membrane that allows saliva to pass through and prevents or inhibits the passage of the matrix composition. The film of the pouch may be any suitable material, such as a woven or nonwoven fabric (e.g., cotton, fleece, etc.), a heat sealable nonwoven cellulosic or other polymeric material, such as a synthetic, semi-synthetic or natural polymeric material. One example of a suitable bag material is paper made from pulp and a small amount of wet strength agent. Materials suitable for use must provide a semipermeable membrane layer to prevent the powder or composition from exiting the bag or pouch during use. Suitable materials are also those which have no significant effect on the release of nicotine from the pouch.
The bag composition is filled into the bag and held in the bag by sealing. The ideal pouch is chemically and physically stable, it is pharmaceutically acceptable, it is water insoluble, it is easy to fill with powder and seal, and it provides a semipermeable membrane layer that prevents powder from exiting the pouch but allows saliva and suspended components such as nicotine from the pouch composition dissolved therein or small enough to pass through the pouch.
The bag may be placed in the mouth by the user. Saliva then enters the pouch where nicotine and other components soluble in the saliva begin to dissolve and pass out of the pouch with the saliva into the oral cavity where the nicotine may be absorbed.
According to one embodiment of the invention, the pouch composition may further comprise one or more additives.
In one embodiment of the invention, the additive is selected from bile salts, docetaxel, chelating agents, citrates, cyclodextrins, detergents, enamine derivatives, fatty acids, labrasol, lecithins, phospholipids, synthetic and natural surfactants, nonionic surfactants, cell envelope disturbing compounds, solvents, steroid detergents, chelating agents, solubilizing agents, charge modifying agents, pH adjusting agents, degrading enzyme inhibitors, mucolytic or mucous clearing agents, membrane penetration enhancers, epithelial junction physiology adjusting agents, vasodilators, selective transport enhancers, or any combination thereof. The pH adjuster includes a buffer.
In one embodiment of the present invention, the additive is selected from cetylpyridinium chloride (CPC), benzalkonium chloride, sodium lauryl sulfate, polysorbate 80, polysorbate 20, cetyltrimethylammonium bromide, laureth 9, sodium salicylate, sodium EDTA, aprotinin, sodium taurocholate, saponin, bile salt derivatives, fatty acids, sucrose esters, azone emulsion, dextran sulfate, linoleic acid, labrafil, transcutol, urea, azone, nonionic surfactant, sulfoxide, salicylic acid/PG, POE 23 lauryl ether, methoxysalicylate, dextran sulfate, methanol, ethanol, sodium cholate, sodium taurocholate, lysophosphatidylcholine, alkyl glycoside, polysorbate, sorbitan ester, poloxamer block copolymer, PEG-35 castor oil PEG-hydrogenated castor oil, caprylocaproyl polyethylene glycol-8 glyceride, PEG-8 caprylic/capric glyceride, dioctyl sulfosuccinate, polyethylene lauryl ether, ethoxydiglycol, propylene glycol, mono-di-caprylate, glyceryl monocaprylate, glyceryl fatty acid (C.sub.8-C.sub.18) ethoxylated oleic acid, linoleic acid, caprylic/capric glyceride, glyceryl monooleate, glyceryl monolaurate, caprylic capric triglyceride, ethoxylated nonylphenol, PEG- (8-50) stearate, olive oil PEG-6, esters, triolein PEG-6 ester, lecithin, d-alpha tocopheryl polyethylene glycol 1,000 succinate, citric acid, sodium citrate, BRIJ, sodium laurate, 5-methoxysalicylic acid, bile salts, acetylsalicylate, ZOT, docosahexaenoic acid, alkyl glycoside, sodium glycocholate (GC-Na), sodium taurocholate (TC-Na), EDTA, choline salicylate, sodium caprate (Cap-Na), N-lauryl- β -D-maltopyranoside (LM), diethyl maleate, labrasol, sodium salicylate, menthol, alkali metal alkyl sulfate, sodium dodecyl sulfate, glycerol, cholic acid, lecithin, phosphatidylcholine, phosphatidylserine, sphingomyelin, phosphatidylethanolamine, cephalin, lysolecithin, hyaluronic acid: alkali metal salts, sodium, alkaline earth metals and aluminum, octylphenoxy polyethoxy ethanol, glycolic acid, lactic acid, chamomile extract, cucumber extract, borage oil, evening primrose oil, polyglycerol, lysine, polylysine, triolein, monoolein, monolaurate, polydonol alkyl ether, chenodeoxycholate, deoxycholate, glycocholic acid, taurocholate, glycodeoxycholic acid, taurodeoxycholic acid, sodium glycocholate, phosphatidylcholine, phosphatidylserine, sphingomyelin, phosphatidylethanolamine, cephalin, lysolecithin, alkali metal hyaluronate, chitosan, poly-L-arginine, alkyl glucosides, sugar alkyl esters Fusarium acid derivatives, sodium Taurinate (STDHF), didecanoyl L-alpha-phosphatidylcholine (DDPC), nitroglycerin, sodium nitroprusside, NOC5[3- (2-hydroxy-1- (methyl-ethyl) -2-nitrosohydrazino) -1-propylamine ], NOC12[ N-ethyl-2- (1-ethyl-hydroxy-2-nitrosohydrazino) -ethylamine, SNAP [ S-nitroso-N-acetyl-DL-penicillamine, NORI, NOR4, deacylated methyl sulfoxide (deacylmethyl sulfoxide), azone, salicylamide, glyceryl-1, 3-diacetoacetate, 1, 2-isopropylideneglycerin-3-acetoacetate), amino acid salt, monoaminocarboxylic acid, glycine, alanine, phenylalanine, proline, hydroxyproline, hydroxyamino acid, amino acid, serine, acidic amino acid, aspartic acid, glutamic acid, basic amino acid, lysine, N-acetylamino acid, 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, pyrrolidone carboxylic acid, alkylpyrrolidone carboxylic acid ester, N-alkylpyrrolidone, proline acyl ester, sodium lauryl phosphate, sodium lauryl sulfate, sodium oleyl phosphate, sodium myristyl sulfate, polyoxyethylene alkyl ether, polyoxyethylene alkyl ester, caproic acid, alkyl sugar, fusidic acid, polyethylene glycol, cetyl alcohol, polyvinylpyrrolidone, polyvinyl alcohol, lanolin alcohol, sorbitan monooleate, ethylene glycol tetraacetic acid, cholic acid-taurine conjugate, cholanic acid and salts, cyclodextrins (β), hydroxypropyl- β -cyclodextrin, sulfobutyl ether- β -cyclodextrin, chitosan glutamate, chitosan acetate, chitosan hydrochloride, chitosan hydrogen lactate (chitosan hydrolactate), 1-O-alkyl-2-hydroxy-sn-glycerol-3-phosphorylcholine, 3-O-alkyl-2-acetyl-sn-glycerol-1-phosphorylcholine, 1-O-alkyl-2-O-acetyl-sn-glycerol-3-phosphate (N, n, N-trimethyl) hexanolamine, propylene glycol, tetradecyl maltoside (TDM), sucrose decanoate.
As used herein, the term "pH adjuster" refers to an agent that actively adjusts and regulates the pH of a solution to which they have been added or to which they are to be added. Thus, the pH adjuster may be an acid and a base, including an acidic buffer and a basic buffer. On the other hand, pH adjusters do not include substances and compositions that affect pH by dilution alone. In addition, the pH adjuster does not include, for example, a flavoring agent, a filler, and the like.
In one embodiment of the invention, the pH adjusting agent is selected from acetic acid, adipic acid, citric acid, fumaric acid, glucono-delta-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, potassium carbonate, calcium carbonate, magnesium oxide, tromethamine, phosphate buffer, amino acid, or any combination thereof.
According to various embodiments of the present invention, one or more sugar alcohols may be contained in the pouch as part of the pouch composition, such as a carrier or part thereof or as a sweetener. Suitable sugar alcohols include sugar alcohols selected from the group consisting of: sorbitol, erythritol, xylitol, lactitol, maltitol, mannitol, hydrogenated starch hydrolysates, isomalt or any combination thereof.
In one embodiment of the invention, the pouch composition comprises a high intensity sweetener.
Preferred high intensity sweeteners include, but are not limited to, sucralose, aspartame, salts of acesulfame such as acesulfame potassium, alitame, saccharin and salts thereof, cyclamic acid and salts thereof, glycyrrhizin, dihydrochalcones, thaumatin, monellin (monellin), stevioside, and the like, alone or in combination.
In one embodiment of the invention, the pouch composition comprises a bulk sweetener comprising sugar and/or sugarless components.
In one embodiment of the invention, the pouch composition comprises bulk sweetener in an amount of 1.0 to about 80% by weight of the pouch composition, more typically 5 to about 70% by weight of the pouch composition, more typically 10 to 60% by weight of the pouch composition, or 10-50% by weight of the pouch composition. Bulk sweeteners may act as both sweetener and humectant. In some embodiments, the introduction of certain ingredients may further limit the approximate amount of bulk sweetener.
Sweeteners generally support the flavor profile of the pouch composition.
Sugar sweeteners generally include, but are not limited to, sugar-containing components commonly known in the art of sachets, such as sucrose, dextrose, maltose, sucrose, lactose, sorbose, dextrin, trehalose, D-tagatose, dry invert sugar, fructose, levulose, galactose, corn syrup solids, glucose syrup, hydrogenated glucose syrup, and the like, alone or in combination.
The sweetener may be used in combination with a sugarless sweetener. Generally, sugarless sweeteners include components having sweet taste characteristics but free of commonly known sugars and include, but are not limited to, sugar alcohols such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolysates, maltitol, isomalt, erythritol, lactitol, and the like, alone or in combination.
As used herein, the term "flavor" is understood to have its ordinary meaning in the art. Flavoring agents include liquid and powdered flavoring agents. Thus, the flavoring agent does not of course include sweeteners (such as sugars, sugar alcohols and high intensity sweeteners) or acids that provide pure acidity/acidity, nor compounds that provide pure salty (e.g., naCl) or bitter taste. Flavor enhancers include substances that provide only salty, bitter, or sour tastes. Flavor enhancers thus include, for example, naCl, citric acid, ammonium chloride, and the like.
The flavoring agent may be a natural or synthetic flavoring agent.
In one embodiment of the invention, the pouch composition comprises a flavoring agent. The flavoring agent may generally be present in an amount of 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.
Non-exhaustive examples of flavoring agents suitable for use in embodiments of the present invention are coconut, coffee, chocolate, vanilla, grape fruit, orange, lime, menthol, licorice, caramel, honey, peanut, walnut, cashew, hazelnut, almond, pineapple, strawberry, raspberry, tropical fruit, cherry, cinnamon, peppermint, wintergreen, spearmint, eucalyptus and peppermint fruit essential oils, such as from apple, pear, peach, strawberry, apricot, raspberry, cherry, pineapple and plum essential oils. The essential oil comprises peppermint, spearmint, menthol, eucalyptus, clove oil, bay oil, pimpinella, thyme, cedar leaf oil, nutmeg, and oils of the above fruits.
In various embodiments of the present invention, the pouch composition comprises a composition modifier. Composition modifiers may be added to tailor the properties of the bag composition and/or portions thereof, such as flowability, texture, uniformity, etc.
According to various embodiments, the composition modifier may be selected from the group consisting of metal stearates, modified calcium carbonate, hydrogenated vegetable oils, partially hydrogenated vegetable oils, polyethylene glycols, polyoxyethylene monostearate, animal fats, silicates, silicate dioxide, talc, magnesium stearate, calcium stearate, fumed silica, powdered hydrogenated cottonseed oil, hydrogenated vegetable oils, hydrogenated soybean oil, emulsifiers, triglycerides and mixtures thereof. In particular, metal stearates such as magnesium stearate may be advantageous.
The composition modifier may be added to the pouch composition in various ways.
For example, the composition modifier may be added as a full powder mixture during the last few minutes of final mixing.
Alternatively, the composition modifier may be added after the granulation step of granulating the premix.
Composition modifiers, such as magnesium stearate, may have a sealing effect and may be used to control nicotine release and pouch solubility.
According to one embodiment of the invention, the pouch composition comprises polyvinylpyrrolidone (PVP). The pouch composition may also be free of PVP.
One advantage of the above embodiments may be that a more uniform composition may be obtained.
Examples
Example 1A-preparation of a pouch designed for administration of nicotine
The material of the bag is a heat sealable nonwoven cellulose, such as a long fiber paper. Bags other than in the form of nonwoven cellulosic fabrics may also be used in accordance with the present invention.
The powder is filled into the bag and held in the bag by sealing.
Example 1B-preparation of a pouch designed for administration of nicotine
The material of the bag is made of rayon fibers such as rayon staple fibers from the viscose process. The bag film is heat sealed along its edges except for an opening in one end into the cavity formed by the bag film.
The powder is filled into the bag and held in the bag by sealing.
Example 2: preparation of nicotine premix
Water was charged into a 60 liter planetary Bear Varimixer mixer and nicotine was weighed and added. The mixer was stirred at low speed for 1 minute at ambient temperature. Then the ion exchange resin is weighed
Figure BDA0004217777500000281
IRP64 is added to the mixer. The mixer was turned off and stirred at high speed for 5 minutes, opened and scraped off if necessary. Finally, the mixer was stirred at high speed for a further 5 minutes. The total treatment time was 20 minutes.
Thus, a mixture of nicotine and cation exchange resin was produced from the constituents set forth in the following table.
Premix I:
composition of components Quantity (kg) Quantity (%)
Nicotine 1.0 5.7
Water and its preparation method 12.5 71.4
Resin composition 4.0 22.9
Totals to 17.5 100.0
Table 1. Ingredients used to make nicotine premix I (5.7% nicotine). % of water in the resulting nicotine-resin composition: 71.4
Premix II:
composition of components Quantity (kg) Quantity (%)
Nicotine 1.08 13.2
Water and its preparation method 2.80 34.1
Resin composition 4.32 52.7
Totals to 8.20 100.0
Table 2. Ingredients used to make nicotine premix II (13.2% nicotine).
% of water in the resulting nicotine-resin composition: 34.1.
premix III:
composition of components Quantity (kg) Quantity (%)
Nicotine 1.08 18.5
Water and its preparation method 0.44 7.5
Resin composition 4.32 74.0
Totals to 5.84 100.0
Table 3. Ingredients used to make nicotine premix III (18.5% nicotine). % of water in the resulting nicotine-resin composition: 7.5.
Premix IV:
composition of components Quantity (kg) Quantity (%)
Nicotine 1.08 10.0
Water and its preparation method 5.40 50.0
Resin composition 4.32 40.0
Totals to 10.8 100.0
Table 4. Ingredients used to make nicotine premix IV (10% nicotine). % of water in the resulting nicotine-resin composition: 50.0.
premix V:
composition of components Quantity (kg) Quantity (%)
Nicotine 1.78 20.0
Water and its preparation method 2.80 31.5
Resin composition 4.32 48.5
Totals to 8.90 100.0
Table 5. Ingredients used to make nicotine premix V (20% nicotine). % of water in the resulting nicotine-resin composition: 31.5.
premix VI:
Figure BDA0004217777500000291
Figure BDA0004217777500000301
table 6. Ingredients used to make nicotine premix VI (30% nicotine). % of water in the resulting nicotine-resin composition: 27.5.
premix VII
Composition of components Quantity (kg) Quantity (%)
Nicotine 3.83 35.0
Water and its preparation method 2.80 25.6
Resin composition 4.32 39.4
Totals to 10.95 100.0
Table 7. Ingredients used to make nicotine premix VII (35% nicotine). % of water in the resulting nicotine-resin composition: 25.6.
premix VIII:
composition of components Quantity (kg) Quantity (%)
Nicotine 5.15 42.0
Water and its preparation method 2.80 22.8
Resin composition 4.32 35.2
Totals to 12.27 100.0
Table 8. Ingredients used to make nicotine premix VIII (42% nicotine). % of water in the resulting nicotine-resin composition: 22.8.
example 3: preparation of bag compositions
Bags containing the powdered compositions as listed in tables 9-21 were prepared. Bags were prepared as follows.
The fibers and water were mixed for 5 minutes using a planetary Bear Varimixer. Then, the following ingredients were subsequently added with continuous mixing: first the nicotine-ion exchange combination (NPR or premix) (2 minutes of mixing), then the remaining ingredients (2 minutes of mixing) except for the liquid flavor and glidant (if any), then the liquid flavor (if any) (1 minute of mixing), then the glidant (if any) (1 minute of mixing). The total mixing time was 9-11 minutes.
Example 4: preparation of filled bags
The final bag composition was filled into bags (target fill weight 500mg of powder per bag). The pouch material of example 1A or 1B may be used. The powder is filled into the bag and held in the bag by sealing.
Example 5A: bag(s)
Bag compositions were prepared from the ingredients in table 9 using the preparation method described in example 3.
The bag composition was filled into bags as described in example 4 (using the bag material of example 1A, but 1B could also be applied).
Figure BDA0004217777500000311
Table 9: a pouch composition.
* The inorganic divalent cations are presented in equivalent numbers relative to nicotine in the nicotine ion exchange combination.
* Divalent cations may be provided as hydrated salts such as dihydrate, tetrahydrate, hexahydrate, etc. The weight% in the table is based on the non-hydrated salt.
Bag contents: in total 500mg, i.e. a nicotine concentration of 19.2mg/g.
Wheat fiber, trade name "Vitace 600WF plus". Other fibers such as water insoluble plant fibers, such as oat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, powdered cellulose, bran fiber, bamboo fiber, and cellulose fiber may also be used.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may be used in combination with or as an alternative to sodium alginate, glycerin, or HPC.
Sodium carbonate was used as alkaline buffer. Other buffers as described herein may also be used in combination with or in place of sodium carbonate.
For example, mixtures of menthol and peppermint may be used as flavoring agents. Of course, other flavors as described herein may also be used in combination with or in place of menthol and/or peppermint. The flavoring may be liquid or flavored or a combination, i.e., liquid flavoring and powdered flavoring are added.
As one example, acesulfame potassium and/or sucralose may be used as high intensity sweeteners. Other useful high intensity sweeteners described herein may be used in combination with or in place of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described herein may be used in combination with or in place of potassium sorbate.
Silica is used as a glidant. Other possible glidants include, for example, magnesium stearate, starch and talc.
Example 5B:
bag compositions were prepared from the ingredients in table 10 using the preparation method described in example 3.
The bag composition was filled into bags as described in example 4 (using the bag material of example 1A, but 1B could also be applied).
Figure BDA0004217777500000321
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Figure BDA0004217777500000331
Table 10: a pouch composition.
* The inorganic divalent cations are presented in equivalent numbers relative to nicotine in the nicotine ion exchange combination.
* Divalent cations may be provided as hydrated salts such as dihydrate, tetrahydrate, hexahydrate, etc. The weight% in the table is based on the non-hydrated salt.
* Corresponds to 1 equivalent of NaCl relative to nicotine in the nicotine ion exchange combination.
* Corresponds to 10 equivalents of NaCl relative to nicotine in the nicotine ion exchange combination.
Bag contents: in total 500mg, i.e. a nicotine concentration of 19.2mg/g.
Wheat fiber, trade name "Vitace 600WF plus". Other fibers such as water insoluble plant fibers, such as oat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, powdered cellulose, bran fiber, bamboo fiber, and cellulose fiber may also be used.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may be used in combination with or as an alternative to sodium alginate, glycerin, or HPC.
Sodium carbonate was used as alkaline buffer. Other buffers as described herein may also be used in combination with or in place of sodium carbonate.
For example, mixtures of menthol and peppermint may be used as flavoring agents. Of course, other flavors as described herein may also be used in combination with or in place of menthol and/or peppermint. The flavoring may be liquid or flavored or a combination, i.e., liquid flavoring and powdered flavoring are added.
As one example, acesulfame potassium and/or sucralose may be used as high intensity sweeteners. Other useful high intensity sweeteners described herein may be used in combination with or in place of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described herein may be used in combination with or in place of potassium sorbate.
Silica is used as a glidant. Other possible glidants include, for example, magnesium stearate, starch and talc.
Example 5C:
bag compositions were prepared from the ingredients in table 11 using the preparation method described in example 3.
The bag composition was filled into bags as described in example 4 (using the bag material of example 1A, but 1B could also be applied).
Figure BDA0004217777500000341
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Figure BDA0004217777500000351
Table 11: a pouch composition.
* The inorganic cations are presented in equivalent numbers relative to nicotine in the nicotine ion exchange combination.
* The multivalent cations may be provided as hydrated salts such as dihydrate, tetrahydrate, hexahydrate, etc. The weight% in the table is based on the non-hydrated salt.
Bag contents: total 500mg.
Wheat fiber, trade name "Vitace 600WF plus". Other fibers such as water insoluble plant fibers, such as oat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, powdered cellulose, bran fiber, bamboo fiber, and cellulose fiber may also be used.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may be used in combination with or as an alternative to sodium alginate, glycerin, or HPC.
Sodium carbonate was used as alkaline buffer. Other buffers as described herein may also be used in combination with or in place of sodium carbonate.
For example, mixtures of menthol and peppermint may be used as flavoring agents. Of course, other flavors as described herein may also be used in combination with or in place of menthol and/or peppermint. The flavoring may be liquid or flavored or a combination, i.e., liquid flavoring and powdered flavoring are added.
As one example, acesulfame potassium and/or sucralose may be used as high intensity sweeteners. Other useful high intensity sweeteners described herein may be used in combination with or in place of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described herein may be used in combination with or in place of potassium sorbate.
Silica is used as a glidant. Other possible glidants include, for example, magnesium stearate, starch and talc.
Example 5D:
bag compositions were prepared from the ingredients in table 12 using the preparation method described in example 3.
The bag composition was filled into bags as described in example 4 (using the bag material of example 1A, but 1B could also be applied).
Figure BDA0004217777500000361
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Figure BDA0004217777500000371
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Figure BDA0004217777500000381
Table 12: a pouch composition.
* The inorganic cations are presented in equivalent numbers relative to nicotine in the nicotine ion exchange combination.
* The multivalent cations may be provided as hydrated salts such as dihydrate, tetrahydrate, hexahydrate, etc. The weight% in the table is based on the non-hydrated salt.
Bag contents: total 500mg.
Wheat fiber, trade name "Vitace 600WF plus". Other fibers such as water insoluble plant fibers, such as oat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, powdered cellulose, bran fiber, bamboo fiber, and cellulose fiber may also be used.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may be used in combination with or as an alternative to sodium alginate, glycerin, or HPC.
Sodium carbonate was used as alkaline buffer. Other buffers as described herein may also be used in combination with or in place of sodium carbonate.
For example, mixtures of menthol and peppermint may be used as flavoring agents. Of course, other flavors as described herein may also be used in combination with or in place of menthol and/or peppermint. The flavoring may be liquid or flavored or a combination, i.e., liquid flavoring and powdered flavoring are added.
As one example, acesulfame potassium and/or sucralose may be used as high intensity sweeteners. Other useful high intensity sweeteners described herein may be used in combination with or in place of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described herein may be used in combination with or in place of potassium sorbate.
Silica is used as a glidant. Other possible glidants include, for example, magnesium stearate, starch and talc.
Example 5E:
bag compositions were prepared from the ingredients in table 13 using the preparation method described in example 3.
The bag composition was filled into bags as described in example 4 (using the bag material of example 1A, but 1B could also be applied).
Figure BDA0004217777500000391
Table 13: a pouch composition.
* The inorganic divalent cations are presented in equivalent numbers relative to nicotine in the nicotine ion exchange combination.
* Divalent cations may be provided as hydrated salts such as dihydrate, tetrahydrate, hexahydrate, etc. The weight% in the table is based on the non-hydrated salt.
Bag contents: in total 500mg, i.e. a nicotine concentration of 19.2mg/g.
Wheat fiber, trade name "Vitace 600WF plus". Other fibers such as water insoluble plant fibers, such as oat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, powdered cellulose, bran fiber, bamboo fiber, and cellulose fiber may also be used.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may be used in combination with or as an alternative to sodium alginate, glycerin, or HPC.
Sodium carbonate was used as alkaline buffer. Other buffers as described herein may also be used in combination with or in place of sodium carbonate.
For example, mixtures of menthol and peppermint may be used as flavoring agents. Of course, other flavors as described herein may also be used in combination with or in place of menthol and/or peppermint. The flavoring may be liquid or flavored or a combination, i.e., liquid flavoring and powdered flavoring are added.
As one example, acesulfame potassium and/or sucralose may be used as high intensity sweeteners. Other useful high intensity sweeteners described herein may be used in combination with or in place of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described herein may be used in combination with or in place of potassium sorbate.
Silica is used as a glidant. Other possible glidants include, for example, magnesium stearate, starch and talc.
Example 5F:
bag compositions were prepared from the ingredients in table 14 using the preparation method described in example 3.
The bag composition was filled into bags as described in example 4 (using the bag material of example 1A, but 1B could also be applied).
Figure BDA0004217777500000401
Figure BDA0004217777500000411
Table 14: a pouch composition.
* The inorganic divalent cations are presented in equivalent numbers relative to nicotine in the nicotine ion exchange combination.
* Divalent cations may be provided as hydrated salts such as dihydrate, tetrahydrate, hexahydrate, etc. The weight% in the table is based on the non-hydrated salt.
Bag contents: in total 500mg, i.e. a nicotine concentration of 19.2mg/g.
Wheat fiber, trade name "Vitace 600WF plus". Other fibers such as water insoluble plant fibers, such as oat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, powdered cellulose, bran fiber, bamboo fiber, and cellulose fiber may also be used.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may be used in combination with or as an alternative to sodium alginate, glycerin, or HPC.
Sodium carbonate was used as alkaline buffer. Other buffers as described herein may also be used in combination with or in place of sodium carbonate.
For example, mixtures of menthol and peppermint may be used as flavoring agents. Of course, other flavors as described herein may also be used in combination with or in place of menthol and/or peppermint. The flavoring may be liquid or flavored or a combination, i.e., liquid flavoring and powdered flavoring are added.
As one example, acesulfame potassium and/or sucralose may be used as high intensity sweeteners. Other useful high intensity sweeteners described herein may be used in combination with or in place of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described herein may be used in combination with or in place of potassium sorbate.
Silica is used as a glidant. Other possible glidants include, for example, magnesium stearate, starch and talc.
Example 5G:
bag compositions were prepared from the ingredients in table 15 using the preparation method described in example 3.
The bag composition was filled into bags as described in example 4 (using the bag material of example 1A, but 1B could also be applied).
Figure BDA0004217777500000421
Figure BDA0004217777500000431
Table 15: a pouch composition.
* The inorganic divalent cations are presented in equivalent numbers relative to nicotine in the nicotine ion exchange combination.
* Divalent cations may be provided as hydrated salts such as dihydrate, tetrahydrate, hexahydrate, etc. The weight% in the table is based on the non-hydrated salt.
Bag contents: in total 500mg, i.e. a nicotine concentration of 19.2mg/g.
Wheat fiber, trade name "Vitace 600WF plus". Other fibers such as water insoluble plant fibers, such as oat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, powdered cellulose, bran fiber, bamboo fiber, and cellulose fiber may also be used.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may be used in combination with or as an alternative to sodium alginate, glycerin, or HPC.
Sodium carbonate was used as alkaline buffer. Other buffers as described herein may also be used in combination with or in place of sodium carbonate.
For example, mixtures of menthol and peppermint may be used as flavoring agents. Of course, other flavors as described herein may also be used in combination with or in place of menthol and/or peppermint. The flavoring may be liquid or flavored or a combination, i.e., liquid flavoring and powdered flavoring are added.
As one example, acesulfame potassium and/or sucralose may be used as high intensity sweeteners. Other useful high intensity sweeteners described herein may be used in combination with or in place of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described herein may be used in combination with or in place of potassium sorbate.
Silica is used as a glidant. Other possible glidants include, for example, magnesium stearate, starch and talc.
Example 5H:
bag compositions were prepared from the ingredients in table 16 using the preparation method described in example 3.
The bag composition was filled into bags as described in example 4 (using the bag material of example 1A, but 1B could also be applied).
Figure BDA0004217777500000441
Table 16: a pouch composition.
* The inorganic divalent cations are presented in equivalent numbers relative to nicotine in the nicotine ion exchange combination.
* Divalent cations may be provided as hydrated salts such as dihydrate, tetrahydrate, hexahydrate, etc. The weight% in the table is based on the non-hydrated salt.
Bag contents: in total 500mg, i.e. a nicotine concentration of 19.2mg/g.
Wheat fiber, trade name "Vitacel 600WF plus" or "Vitacel 200WF".
Powdered cellulose, trade name "Vitacel L00" or "Vitacel L700G".
Oat fiber, trade name "Vitacel HF 600".
Pea fiber, trade name "Vitacel EF150".
Other fibers such as water insoluble plant fibers, such as oat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, powdered cellulose, cellulose fiber, apple fiber, cocoa fiber, bamboo fiber, bran fiber, and cellulose fiber may also be used.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may be used in combination with or as an alternative to sodium alginate, glycerin, or HPC.
Sodium carbonate was used as alkaline buffer. Other buffers as described herein may also be used in combination with or in place of sodium carbonate.
For example, mixtures of menthol and peppermint may be used as flavoring agents. Of course, other flavors as described herein may also be used in combination with or in place of menthol and/or peppermint. The flavoring may be liquid or flavored or a combination, i.e., liquid flavoring and powdered flavoring are added.
As one example, acesulfame potassium and/or sucralose may be used as high intensity sweeteners. Other useful high intensity sweeteners described herein may be used in combination with or in place of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described herein may be used in combination with or in place of potassium sorbate.
Silica is used as a glidant. Other possible glidants include, for example, magnesium stearate, starch and talc.
Example 5I:
bag compositions were prepared from the ingredients in table 17 using the preparation method described in example 3.
The bag composition was filled into bags as described in example 4 (using the bag material of example 1A, but 1B could also be applied).
Figure BDA0004217777500000451
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Figure BDA0004217777500000461
Table 17: a pouch composition.
* The inorganic divalent cations are presented in equivalent numbers relative to nicotine in the nicotine ion exchange combination.
* Divalent cations may be provided as hydrated salts such as dihydrate, tetrahydrate, hexahydrate, etc. The weight% in the table is based on the non-hydrated salt.
Bag contents: in total 500mg, i.e. a nicotine concentration of 19.2mg/g.
Wheat fiber, trade name "Vitacel 600WF plus" or "Vitacel 200WF".
Powdered cellulose, trade name "Vitacel L00" or "Vitacel L700G".
Oat fiber, trade name "Vitacel HF 600".
Pea fiber, trade name "Vitacel EF150".
Other fibers such as water insoluble plant fibers, such as oat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, powdered cellulose, cellulose fiber, apple fiber, cocoa fiber, bamboo fiber, bran fiber, and cellulose fiber may also be used.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may be used in combination with or as an alternative to sodium alginate, glycerin, or HPC.
Sodium carbonate was used as alkaline buffer. Other buffers as described herein may also be used in combination with or in place of sodium carbonate.
For example, mixtures of menthol and peppermint may be used as flavoring agents. Of course, other flavors as described herein may also be used in combination with or in place of menthol and/or peppermint. The flavoring may be liquid or flavored or a combination, i.e., liquid flavoring and powdered flavoring are added.
As one example, acesulfame potassium and/or sucralose may be used as high intensity sweeteners. Other useful high intensity sweeteners described herein may be used in combination with or in place of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described herein may be used in combination with or in place of potassium sorbate.
Silica is used as a glidant. Other possible glidants include, for example, magnesium stearate, starch and talc.
Example 5J:
bag compositions were prepared from the ingredients in table 18 using the preparation method described in example 3.
The bag composition was filled into bags as described in example 4 (using the bag material of example 1A, but 1B could also be applied).
Figure BDA0004217777500000471
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Figure BDA0004217777500000481
Table 18: a pouch composition.
* The inorganic divalent cations are presented in equivalent numbers relative to nicotine in the nicotine ion exchange combination.
* Divalent cations may be provided as hydrated salts such as dihydrate, tetrahydrate, hexahydrate, etc. The weight% in the table is based on the non-hydrated salt.
Bag contents: in total 500mg, i.e. a nicotine concentration of 19.2mg/g.
Wheat fiber, trade name "Vitace 600WF plus". Other fibers such as water insoluble plant fibers, such as oat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, powdered cellulose, bran fiber, bamboo fiber, and cellulose fiber may also be used.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may be used in combination with or as an alternative to sodium alginate, glycerin, or HPC.
Sodium carbonate was used as alkaline buffer. Other buffers as described herein may also be used in combination with or in place of sodium carbonate.
For example, mixtures of menthol and peppermint may be used as flavoring agents. Of course, other flavors as described herein may also be used in combination with or in place of menthol and/or peppermint. The flavoring may be liquid or flavored or a combination, i.e., liquid flavoring and powdered flavoring are added.
As one example, acesulfame potassium and/or sucralose may be used as high intensity sweeteners. Other useful high intensity sweeteners described herein may be used in combination with or in place of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described herein may be used in combination with or in place of potassium sorbate.
Silica is used as a glidant. Other possible glidants include, for example, magnesium stearate, starch and talc.
Example 5K:
bag compositions were prepared from the ingredients in table 19 using the preparation method described in example 3.
The bag composition was filled into bags as described in example 4 (using the bag material of example 1A, but 1B could also be applied).
Figure BDA0004217777500000491
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Figure BDA0004217777500000501
Table 19: a pouch composition.
* The inorganic divalent cations are presented in equivalent numbers relative to nicotine in the nicotine ion exchange combination.
* Divalent cations may be provided as hydrated salts such as dihydrate, tetrahydrate, hexahydrate, etc. The weight% in the table is based on the non-hydrated salt.
Bag contents: in total 500mg, i.e. a nicotine concentration of 19.2mg/g.
Wheat fiber, trade name "Vitace 600WF plus". Other fibers such as water insoluble plant fibers, such as oat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, powdered cellulose, bran fiber, bamboo fiber, and cellulose fiber may also be used.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may be used in combination with or as an alternative to sodium alginate, glycerin, or HPC.
Sodium carbonate was used as alkaline buffer. Other buffers as described herein may also be used in combination with or in place of sodium carbonate.
For example, mixtures of menthol and peppermint may be used as flavoring agents. Of course, other flavors as described herein may also be used in combination with or in place of menthol and/or peppermint. The flavoring may be liquid or flavored or a combination, i.e., liquid flavoring and powdered flavoring are added.
As one example, acesulfame potassium and/or sucralose may be used as high intensity sweeteners. Other useful high intensity sweeteners described herein may be used in combination with or in place of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described herein may be used in combination with or in place of potassium sorbate.
Silica is used as a glidant. Other possible glidants include, for example, magnesium stearate, starch and talc.
Example 5L:
bag compositions were prepared from the ingredients in table 20 using the preparation method described in example 3.
The bag composition was filled into bags as described in example 4 (using the bag material of example 1A, but 1B could also be applied).
Figure BDA0004217777500000511
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Figure BDA0004217777500000521
Table 20: a pouch composition.
* The inorganic divalent cations are presented in equivalent numbers relative to nicotine in the nicotine ion exchange combination.
* Divalent cations may be provided as hydrated salts such as dihydrate, tetrahydrate, hexahydrate, etc. The weight% in the table is based on the non-hydrated salt.
Bag contents: in total 500mg, i.e. a nicotine concentration of 19.2mg/g (16 mg/g for samples P116, P117 and C12).
Wheat fiber, trade name "Vitace 600WF plus". Powdered cellulose, trade name "powdered cellulose L700G". Other fibers such as water insoluble plant fibers, such as oat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, bran fiber, bamboo fiber, and cellulose fiber may also be used.
Sodium carbonate was used as alkaline buffer. Other buffers as described herein may also be used in combination with or in place of sodium carbonate.
For example, mixtures of menthol and peppermint may be used as flavoring agents. Of course, other flavors as described herein may also be used in combination with or in place of menthol and/or peppermint. The flavoring may be liquid or flavored or a combination, i.e., liquid flavoring and powdered flavoring are added.
As one example, acesulfame potassium and/or sucralose may be used as high intensity sweeteners. Other useful high intensity sweeteners described herein may be used in combination with or in place of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described herein may be used in combination with or in place of potassium sorbate.
Silica is used as a glidant. Other possible glidants include, for example, magnesium stearate, starch and talc.
Example 5M:
bag compositions were prepared from the ingredients in table 21 using the preparation method described in example 3.
The bag composition was filled into bags as described in example 4 (using the bag material of example 1A, but 1B could also be applied).
Figure BDA0004217777500000531
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Figure BDA0004217777500000541
Table 21: a pouch composition.
* The inorganic divalent cations are presented in equivalent numbers relative to nicotine in the nicotine ion exchange combination.
* Divalent cations may be provided as hydrated salts such as dihydrate, tetrahydrate, hexahydrate, etc. The weight% in the table is based on the non-hydrated salt.
Bag contents: in total 500mg, i.e. a nicotine concentration of 19.2mg/g.
Wheat fiber, trade name "Vitace 600WF plus". Other fibers such as water insoluble plant fibers, such as oat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, powdered cellulose, bran fiber, bamboo fiber, and cellulose fiber may also be used.
Sodium alginate, glycerol and hydroxypropyl cellulose (HPC) may be used as humectants. Other humectants as described herein may be used in combination with or as an alternative to sodium alginate, glycerin, or HPC.
Sodium carbonate was used as alkaline buffer. Other buffers as described herein may also be used in combination with or in place of sodium carbonate.
For example, mixtures of menthol and peppermint may be used as flavoring agents. Of course, other flavors as described herein may also be used in combination with or in place of menthol and/or peppermint. The flavoring may be liquid or flavored or a combination, i.e., liquid flavoring and powdered flavoring are added.
As one example, acesulfame potassium and/or sucralose may be used as high intensity sweeteners. Other useful high intensity sweeteners described herein may be used in combination with or in place of acesulfame potassium and/or sucralose.
Potassium sorbate is used as a preservative. Other preservatives as described herein may be used in combination with or in place of potassium sorbate.
Silica is used as a glidant. Other possible glidants include, for example, magnesium stearate, starch and talc.
Example 6A: release experiments and different salts.
By adding a certain amount of NPR (16%) and a different number of equivalents of CaCl to 900mL of water 2 To perform a release experiment (corresponding to a nicotine concentration of 28 mg/L). CaCl (CaCl) 2 Is relative to nicotine. The temperature of the water was 25 degrees celsius throughout the experiment and stirring at 100rpm was applied throughout the experiment. The pH was measured at the beginning and end of the experiment. At the beginning and end of the experiment, the pH was below 7.0 in all experiments.
Relatively low nicotine concentrations are used to reduce the effect of equilibrium on the release rate and effective release of nicotine from the ion exchange resin.
Samples were taken at various time points and analyzed for nicotine content using standard HPLC. Results are presented as a percentage of nicotine released.
Figure BDA0004217777500000551
Figure BDA0004217777500000561
Table 22: nicotine release over time in the presence of different salts and different equivalent numbers of cations.
Evaluation: the results indicate that CaCl 2 The presence of (2) significantly increases the release of nicotine from NPR. Increasing CaCl 2 Resulting in an increased release of nicotine. CaCl (CaCl) 2 The presence of (a) both increases the initial release rate and appears to increase the effective release of nicotine.
Furthermore, the results show that NaCl has a much lower effect on nicotine release, and therefore a large amount of NaCl is required to achieve the same effect as in the presence of e.g. 1 equivalent CaCl 2 Is equivalent to nicotine release.
Example 6B: using NPR and CaCl of varying equivalent numbers 2 Release experiments of (a).
By adding NPR (16%) and CaCl of different equivalent numbers to a volume of water 2 To perform a release experiment (corresponding to a nicotine concentration of 28 mg/L). CaCl (CaCl) 2 Is relative to nicotine. The temperature of the water was 25 degrees celsius throughout the experiment and stirring at 100rpm was applied throughout the experiment. The pH was measured at the beginning and end of the experiment. At the beginning and end of the experiment, the pH was below 7.0 in all experiments.
Relatively low nicotine concentrations are used to reduce the effect of equilibrium on the release rate and effective release of nicotine from the ion exchange resin.
Samples were taken at various time points and analyzed for nicotine content using standard HPLC. Results are presented as a percentage of nicotine released.
Figure BDA0004217777500000562
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Figure BDA0004217777500000571
Table 23: showing the presence of different equivalent numbers of CaCl 2 The percentage of nicotine released from NPR at different time points.
Evaluation: the results indicate that CaCl 2 The presence of (2) significantly increases the release of nicotine from NPR. Increasing CaCl 2 Resulting in an increased release of nicotine. CaCl (CaCl) 2 The presence of (a) both increases the initial release rate and appears to increase the effective release of nicotine.
Example 6C: using NPR and MgCl of different equivalent numbers 2 Release experiments of (a).
By adding NPR (16%) and MgCl with different equivalent numbers to a volume of water 2 To perform a release experiment (corresponding to a nicotine concentration of 28 mg/L). MgCl 2 Is relative to nicotine. The temperature of the water was 25 degrees celsius throughout the experiment and stirring at 100rpm was applied throughout the experiment. The pH was measured at the beginning and end of the experiment. At the beginning and end of the experiment, the pH was below 7.0 in all experiments.
Relatively low nicotine concentrations are used to reduce the effect of equilibrium on the release rate and effective release of nicotine from the ion exchange resin.
Samples were taken at various time points and analyzed for nicotine content using standard HPLC. Results are presented as a percentage of nicotine released.
Figure BDA0004217777500000581
Table 24: showing the presence of MgCl in different equivalent numbers 2 The percentage of nicotine released from NPR at different time points.
Evaluation: the results show that MgCl 2 The presence of (2) significantly increases the release of nicotine from NPR. Increasing MgCl 2 Resulting in an increased release of nicotine. MgCl 2 The presence of (a) both increases the initial release rate and appears to increase the effective release of nicotine. The results were comparable to those presented in example 6B.
Example 6D: using 1 equivalent of CaCl 2 And release experiments of nicotine premixes with different nicotine content.
By adding CaCl with different nicotine content and 1 equivalent to a volume of water 2 The release experiments were performed whereby a corresponding nicotine concentration of 28mg/L was obtained. CaCl (CaCl) 2 Is relative to nicotine. The temperature of the water was 25 degrees celsius throughout the experiment and 150 degrees celsius was applied throughout the experimentStirring at rpm. The pH was measured at the beginning and end of the experiment. At the beginning and end of the experiment, the pH was below 7.0 in all experiments.
Relatively low nicotine concentrations are used to reduce the effect of equilibrium on the release rate and effective release of nicotine from the ion exchange resin.
Samples were taken at various time points and analyzed for nicotine content using standard HPLC. Results are presented as a percentage of nicotine released.
Figure BDA0004217777500000582
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Figure BDA0004217777500000591
Table 25: showing the presence of 1 equivalent of MgCl 2 The percentage of nicotine released from the nicotine premix at different time points.
Evaluation: the results indicate that CaCl 2 The presence of (2) significantly increases the release of nicotine from the premix. CaCl (CaCl) 2 The presence of (a) both increases the initial release rate and appears to increase the effective release of nicotine. Furthermore, the results show that increasing the nicotine content of the premix also increases the nicotine release.
Example 6E: 1 equivalent of AlCl is used 3 Release experiments of (a).
By adding NPR (16%) and 1 equivalent of AlCl to a volume of water 3 To perform a release experiment (corresponding to a nicotine concentration of 28 mg/L). The number of equivalents is relative to nicotine. The temperature of the water was 25 degrees celsius throughout the experiment and 150rpm agitation was applied throughout the experiment. The pH was measured at the beginning and end of the experiment. At the beginning and end of the experiment, the pH was below 7.0 in all experiments.
Relatively low nicotine concentrations are used to reduce the effect of equilibrium on the release rate and effective release of nicotine from the ion exchange resin.
Samples were taken at various time points and analyzed for nicotine content using standard HPLC. Results are presented as a percentage of nicotine released.
Figure BDA0004217777500000601
Table 24: showing the presence of 1 equivalent of AlCl 3 The percentage of nicotine released from NPR at different time points.
Evaluation: the results show 1 equivalent of AlCl 3 The presence of (2) significantly increases the release of nicotine from NPR. AlCl 3 The presence of (a) both increases the initial release rate and appears to increase the effective release of nicotine.
Example 7A: bag release test (in vitro)
The release properties of the pouches were tested in vitro experiments.
The reaction tube, approximately 2cm in diameter, containing 10mL of 0.02M potassium dihydrogen phosphate buffer (pH adjusted to 7.4) was warmed to 37 degrees Celsius. One reaction tube was used at each time point.
The bag was immersed in the buffer of the first reaction tube using tweezers. After the indicated period of time, the bag was gripped with forceps and gently vortexed in buffer, then removed from the first reaction tube and added to the next reaction tube, which represents the next time point. The procedure was repeated until the desired number of time points were tested.
The entire release experiment was performed at 37 degrees celsius. No stirring or shaking was applied during the release experiment.
The amount of nicotine released was determined by analyzing buffer samples at different time points using standard HPLC.
Example 8A: release test on bags
The release experiments were performed as described in example 7A.
Figure BDA0004217777500000611
Table 27A: showing the presence of different equivalent numbers of CaCl 2 Is the case of (1)The percentage of nicotine released from the nicotine pouch at different time points.
Figure BDA0004217777500000612
Table 27B: showing the presence of different equivalent numbers of CaCl 2 The percentage of nicotine released from the nicotine pouch at different time points.
Evaluation: p110 and P113 were compared to C10 and C11, respectively, and the results showed CaCl 2 Is present to increase the release of nicotine from the pouch. This was also confirmed by comparison of P116 with C12. CaCl (CaCl) 2 The presence of (a) both increases the initial release rate and appears to increase the effective release of nicotine. Comparing P40 with P42 and P116 with P117, confirming the increase in CaCl in the bag 2 Also increasing the release of nicotine from the pouch. In addition, it should be noted that the desired improved release results have been demonstrated with various formulations comprising different fibers (here wheat fiber and powdered cellulose).
Furthermore, comparing P40 with P43, P42 with P45 and P110 with P113, the results indicate that increasing the nicotine content of the premix also increases the release of nicotine from the pouch.
Finally, it should be pointed out that, in order to obtain and never contain only 0.75 equivalent CaCl 2 The equivalent release obtained for the bags of (a) will require a much higher amount of NaCl, where at least 2.9 equivalents of NaCl are required to achieve a CaCl equivalent of 0.75 2 Comparable release (see C4, C5, P40 and P43).
Example 9A: and (5) evaluating by a user.
The resulting pouches of the present invention were evaluated and found to be highly suitable as delivery vehicles for nicotine as they provide good nicotine release while being pleasant to the user, e.g. in terms of desired mouthfeel such as wet and plastic structure and desired taste.
Example 9B: and (5) evaluating by a user.
The pouch products P03, P44 and P117 were evaluated in terms of nicotine perception effect and mouthfeel.
The nicotine perception effect and mouthfeel were evaluated as follows.
Nicotine perception and mouthfeel were evaluated by a test panel consisting of 4 trained evaluators. Each evaluator evaluates all samples twice. The average evaluation is estimated.
All four evaluators evaluated that the pouch products P03, P44 and P117 were fast acting and had a high nicotine perception effect. In addition, all four evaluators rated the bag product to have the desired mouthfeel, i.e., the bag was found to be moist and to have the desired taste.
Bags P08 and P127 were similarly evaluated. All four evaluators evaluated that the bags were fast acting and had a high perceived effect of nicotine. However, these bags were found to provide a less desirable mouthfeel, which were perceived as somewhat dry, adhering to the oral mucosa and/or having an unpleasant or less desirable taste, i.e. too salty.
Pouches comparable to P127 but containing higher amounts of flavoring, i.e., P128 and P129, were also evaluated. Although their flavor levels increased compared to P127, these pouches were also perceived as dry and adhered to the oral mucosa. Furthermore, it was found that the taste of these bags was less desirable because salty taste notes were still perceived and the flavor profile was perceived as unbalanced.
These observations indicate that the less desirable mouthfeel and taste effects associated with high levels of inorganic divalent cations cannot be offset by increasing the level of flavoring in the pouch composition. That is, simply masking the taste by means of high levels of flavoring agents does not counteract the adverse effects at high levels of inorganic divalent cations.

Claims (63)

1. A pouch composition comprising
A nicotine-ion exchange resin combination, wherein,
water in an amount of at least 15% by weight of the pouch composition, and
inorganic divalent cations.
2. The pouch composition of claim 1, wherein the pouch composition comprises inorganic divalent cations in a 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.
3. A pouch composition according to claim 1 or 2, wherein the pouch composition comprises inorganic divalent cations in a molar ratio of at most 6.5 with respect to the amount of nicotine in the nicotine-ion exchange resin combination, such as at most 6 with respect to the amount of nicotine in the nicotine-ion exchange resin combination, such as at most 5 with respect to the amount of nicotine in the nicotine-ion exchange resin combination, such as at most 3.75 with respect to the amount of nicotine in the nicotine-ion exchange resin combination, such as at most 2.5 with respect to the amount of nicotine in the nicotine-ion exchange resin combination.
4. A pouch composition according to any of claims 1-3, wherein the inorganic divalent cation is selected from divalent cations of calcium, magnesium, iron, zinc, and any combination thereof.
5. The pouch composition of any of claims 1-4, wherein the inorganic divalent cation is selected from divalent cations of calcium and magnesium.
6. The pouch composition of any of claims 1-5, wherein the inorganic divalent cation is provided as a salt comprising an anion selected from the group consisting of: carboxylate, such as acetate, lactate, oxalate, propionate or levulinate; an organic sulfonate group; organic sulfate radicals; an organic phosphate group; chloride, bromide, nitrate, sulfate, hydrogen phosphate, oxygen ions, and any combination thereof.
7. The pouch composition of any of claims 1-6, wherein the inorganic divalent cation is provided as an inorganic salt.
8. The pouch composition of any of claims 1-7, wherein the inorganic divalent cation is provided as a salt in an amount between 0.1 and 15.0 wt% of the composition, such as between 0.1 and 10.0 wt% of the composition, such as between 0.5 and 10.0 wt% of the composition.
9. The pouch composition according to any one of claims 1-8, wherein the inorganic divalent cation is provided as an inorganic salt comprising an inorganic anion selected from the group consisting of: chloride, bromide, nitrate, sulfate, bicarbonate, hydrogen phosphate, oxygen, hydroxide, and any combination thereof.
10. The pouch composition according to any one of claims 1-9, wherein the inorganic divalent cation is provided as an inorganic salt comprising an inorganic anion selected from the group consisting of: chloride, bromide, bicarbonate, sulfate, and any combination thereof.
11. The pouch composition according to any one of claims 1-10, wherein the inorganic divalent cation is provided as an inorganic salt comprising an inorganic anion selected from the group consisting of: chloride, bromide, and any combination thereof.
12. The pouch composition of any of claims 1-11, wherein the inorganic anion comprises chloride ions.
13. The pouch composition according to any of claims 1-12, wherein the inorganic divalent cation is provided as an inorganic salt selected from calcium chloride or magnesium chloride or a combination thereof.
14. The pouch composition of any of claims 1-13, wherein the divalent cation is provided as a water soluble salt having a water solubility of at least 5 grams per 100mL of water measured at 25 degrees celsius, atmospheric pressure, and pH 7.0.
15. The pouch composition of any of claims 1-14, wherein the pouch composition comprises nicotine in an amount of at least 0.1% by weight of the pouch composition, such as at least 0.2% by weight.
16. The pouch composition of any of claims 1-15, wherein the pouch composition comprises a nicotine-ion exchange combination in an amount of 0.1 to 20% by weight of the pouch composition.
17. The pouch composition of any of claims 1-16, wherein the nicotine-ion exchange resin combination comprises nicotine in an amount of between 5 and 50% by weight.
18. The pouch composition of any of claims 1-17, wherein the nicotine-ion exchange resin combination comprises between 5 and 50% nicotine by weight and between 10 and 95% ion exchange resin by weight.
19. The pouch composition of any of claims 1-18, wherein the ion exchange resin comprises one or more resins selected from the group consisting of:
(i) Methacrylic weak acid type resin containing carboxylic acid type functional group,
(ii) A copolymer of methacrylic acid and divinylbenzene, said copolymer containing carboxylic acid-based functional groups,
(iii) A strongly acidic type of polystyrene resin containing sulfonic acid-based functional groups,
(iv) A resin of medium acidic type in polystyrene containing phosphoric acid-based functional groups, and
(v) A combination thereof.
20. The pouch composition of any of claims 1-19, wherein the ion exchange resin comprises a polyirine resin.
21. The pouch composition of any of claims 1-20, wherein the ion exchange resin is a polyirine resin.
22. The pouch composition of any of claims 1-21, wherein the nicotine-ion exchange resin combination comprises nicotine complexed with an ion exchange resin.
23. The pouch composition of any of claims 1-22, wherein the nicotine-ion exchange resin combination is nicotine complexed with an ion exchange resin.
24. The pouch composition of any of claims 1-23, wherein the nicotine-ion exchange resin combination comprises free base nicotine mixed with an ion exchange resin.
25. The pouch composition of any of claims 1-24, wherein 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 20-40% by weight of the composition, such as 25-35% by weight of the composition.
26. The pouch composition of any of claims 1-25, wherein the pouch composition comprises at least one sugar alcohol.
27. The pouch composition of any of claims 1-26, wherein the at least one sugar alcohol is selected from xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and mixtures thereof.
28. The pouch composition of any of claims 1-27, wherein the pouch composition comprises at least two sugar alcohols.
29. The pouch composition of any of claims 1-28, wherein the pouch composition comprises a 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.
30. The pouch composition of any of claims 1-29, wherein 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.
31. The pouch composition of any of claims 1-30, wherein the pouch composition comprises at least one water insoluble fiber.
32. The pouch composition of any of claims 1-31, wherein the pouch composition comprises the water insoluble fiber in an amount of between 5 to 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.
33. The pouch composition of any of claims 1-32, wherein the water insoluble fiber is a plant fiber.
34. The pouch composition of any of claims 1-33, wherein the water insoluble fiber is selected from the group consisting of wheat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, beet fiber, buckwheat fiber, potato fiber, cellulose fiber, apple fiber, cocoa fiber, cellulose fiber, bran fiber, bamboo fiber, powdered cellulose, and combinations thereof.
35. The pouch composition of any of claims 1-34, wherein the water insoluble fiber has a water binding capacity of at least 200%, such as at least 300%, such as at least 400%.
36. The pouch composition of any of claims 1-35, wherein the water insoluble fiber has a density of 50 to 500 g/l, such as 100 to 400 g/l, such as 200 to 300 g/l.
37. The pouch composition of any of claims 1-36, wherein the pouch composition comprises a pH adjuster.
38. The pouch composition of any of claims 1-37, wherein the pouch composition comprises a pH adjuster in an amount of between 0.01 to 15% by weight of the pouch composition, such as between 0.5 to 10% by weight of the pouch composition, such as between 1 to 10% by weight of the pouch composition, such as between 5 to 10% by weight of the pouch composition.
39. The pouch composition of any of claims 1-38, wherein the pH adjustor is an alkaline pH adjustor, such as an alkaline buffer.
40. The pouch composition of any of claims 1-39, wherein the pH adjustor is a buffer, such as an alkaline buffer.
41. The pouch composition of any of claims 1-40, wherein the pH adjustor is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, and magnesium carbonate; potassium bicarbonate; tromethamine; phosphate buffer, amino acid, or any combination thereof.
42. The pouch composition of any of claims 1-41, wherein the pH adjustor is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, and magnesium carbonate; potassium bicarbonate; tromethamine; phosphate buffer, or any combination thereof.
43. The pouch composition of any of claims 1-42, wherein the pH adjustor is selected from the group consisting of tromethamine, an amino acid, and a phosphate buffer, or any combination thereof.
44. The pouch composition of any of claims 1-43, wherein the pH adjustor is selected from the group consisting of tromethamine and phosphate buffer or any combination thereof.
45. The pouch composition of any of claims 1-44, wherein the pH adjustor is tromethamine.
46. The pouch composition of any of claims 1-44, wherein the pH adjustor is a phosphate buffer.
47. The pouch composition of any of claims 1-43, wherein the pH adjustor is an amino acid.
48. The pouch composition of any of claims 1-47, wherein the pouch composition is adapted to release at least 30% of nicotine within 10 minutes upon exposure to the in vitro conditions described in example 7A.
49. The pouch composition of any of claims 1-48, wherein the pouch composition is adapted to release at least 25% more nicotine within 5 minutes than a corresponding pouch composition without divalent cations upon exposure to the in vitro conditions described in example 7A.
50. The pouch composition of any of claims 1-49, wherein the pouch composition comprises a humectant.
51. The pouch composition of any of claims 1-50, wherein the pouch composition comprises sodium chloride in an amount of 0.0-3.0% by weight of the pouch composition, such as 0.05-1.0% by weight of the pouch composition, such as 0.1-1.0% by weight of the pouch composition.
52. The pouch composition of any of claims 1-51, wherein the pouch composition is a non-tobacco pouch composition.
53. The pouch composition according to any of claims 1-51, wherein the pouch composition comprises less than 2.0% by weight tobacco, such as less than 1.0% by weight tobacco, such as less than 0.5% by weight tobacco, such as 0.0% by weight tobacco.
54. The pouch composition of any of claims 1-51, wherein the pouch composition comprises non-tobacco fibers.
55. The pouch composition of any of claims 1-54, wherein the pouch composition is a powdered composition.
56. An oral pouched nicotine product comprising a saliva-permeable pouch and a pouch composition according to any one of claims 1-55 enclosed in the pouch.
57. An oral packaged nicotine product according to claim 56, wherein the packaged nicotine product comprises nicotine in an amount of 0.5 to 20mg, such as 1.0 to 20mg, such as 5.0 to 15 mg.
58. The oral pouched nicotine product of claim 56 or 57, wherein the pouched nicotine product comprises a nicotine-ion exchange combination in an amount of from 1 to 100mg per pouch.
59. A pouch composition comprising
Nicotine-ion exchange resin combination, and
inorganic multivalent cations.
60. The pouch composition of claim 59, wherein the multivalent cation is selected from multivalent ions of calcium, magnesium, zinc, aluminum, barium, iron, manganese, copper, lead, cobalt, nickel, such as ca2+, mg2+, zn2+, al3+, ba2+, fe2+, fe3+, fe4+, mn2+, mn4+, cu4+, or any combination thereof.
61. The pouch composition of claim 59 or 60, wherein the multivalent cation is trivalent.
62. The pouch composition of any of claims 59-61, wherein the multivalent cation is selected from the group consisting of trivalent cations of aluminum, divalent cations of calcium, magnesium, iron, zinc, and any combination thereof.
63. The pouch composition of any of claims 59-60 or 62, wherein the multivalent cation is selected from the group consisting of divalent cations of calcium, magnesium, iron, zinc, and any combination thereof.
CN202180075476.XA 2020-11-16 2021-11-16 Nicotine pouch compositions Pending CN116419682A (en)

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EP20207822.6 2020-11-16
US17/099,446 2020-11-16
US17/099,446 US20220151292A1 (en) 2020-11-16 2020-11-16 Nicotine pouch composition
EP20207822.6A EP4000424B1 (en) 2020-11-16 2020-11-16 Nicotine pouch composition
PCT/DK2021/050334 WO2022100805A1 (en) 2020-11-16 2021-11-16 Nicotine pouch composition

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US11717017B2 (en) * 2017-04-24 2023-08-08 Swedish Match North Europe Ab Flavoured moist oral pouched nicotine product comprising triglyceride
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