Oral products having nicotine-polymer complexes

Abstract

The product that contains nicotine polymer complex is provided herein, and can optionally further comprise one or more different nicotine components.A particular such product is a pouch product that comprises an outer water-permeable pouch that defines a cavity that contains a composition that comprises a water-soluble component that can be released through the water-permeable pouch.The present disclosure also provides a method for preparing such a product.

Description

[Technical field]

[0001] The present disclosure relates to products intended for human use. The products are designed for oral use and to deliver substances such as flavors and / or active ingredients during use. Such products may contain tobacco or tobacco-derived products or may be tobacco-free alternatives. [Background technology]

[0002] There are many categories of products intended for oral use and enjoyment. For example, oral tobacco products containing nicotine are known to have both stimulant and anxiolytic properties and have been available for many years. Traditional formats for so-called "smokeless" tobacco products include moist snuff, snus, and chewing tobacco, which are usually made almost entirely of granular, granular, or shredded tobacco and are either divided by the user or presented to the user in individual portions, such as disposable pouches or sachets. See, for example, the types of smokeless tobacco formulations, ingredients, and processing methods described in U.S. Pat. No. 6,668,839 to Williams; U.S. Pat. No. 6,834,654 to Williams; U.S. Pat. No. 6,953,040 to Atchley et al.; U.S. Pat. No. 7,032,601 to Atchley et al.; and U.S. Pat. No. 7,694,686 to Atchley et al.; U.S. Pat. No. 7,810,507 to Dube et al.; U.S. Pat. No. 7,819,124 to Strickland et al.; U.S. Pat. No. 7,861,728 to Holton, Jr. et al.; U.S. Pat. No. 7,901,512 to Quinter et al.; U.S. Pat. No. 8,627,828 to Strickland et al.; and U.S. Pat. No. 11,246,334 to Atchley, each of which is incorporated herein by reference.

[0003] In addition, traditional tobacco and non-tobacco materials may be combined with other ingredients to form product formats that are distinct from traditional smokeless products, exemplary formats of which include lozenges, pastilles, gels, and the like. See, for example, U.S. Patent Application Publication No. 2008 / 0196730 to Engstrom et al.; U.S. Patent Application Publication No. 2008 / 0305216 to Crawford et al.; U.S. Patent Application Publication No. 2009 / 0293889 to Kumar et al.; U.S. Patent Application Publication No. 2010 / 0291245 to Gao et al.; U.S. Patent Application Publication No. 2011 / 0139164 to Mua et al.; U.S. Patent Application Publication No. 2012 / 0037175 to Cantrell et al.; U.S. Patent Application Publication No. 2012 / 0055494 to Hunt et al.; U.S. Patent Application Publication No. 2012 / 0138073 to Cantrell et al.; See the types of products described in U.S. Patent Application Publication No. 2012 / 0138074 to Rell et al.; U.S. Patent Application Publication No. 2013 / 0074855 to Holton, Jr.; U.S. Patent Application Publication No. 2013 / 0074856 to Holton, Jr.; U.S. Patent Application Publication No. 2013 / 0152953 to Mua et al.; U.S. Patent Application Publication No. 2013 / 0274296 to Jackson et al.; U.S. Patent Application Publication No. 2015 / 0068545 to Moldoveanu et al.; U.S. Patent Application Publication No. 2015 / 0101627 to Marshall et al.; and U.S. Patent Application Publication No. 2015 / 0230515 to Lampe et al.

[0004] There is a continuing interest in developing new types of oral products that deliver beneficial sensory or biological activity.Such products usually contain flavorings and / or active ingredients, such as nicotine, caffeine, botanicals, or cannabidiol.The format of such products may vary, including powdered or granular compositions, lozenges, pastilles, liquids, gels, emulsions, pouch products that contain meltable compositions, etc. See, for example, U.S. Patent Application Publication No. 2022 / 0160675 to Gerardi et al.; U.S. Patent Application Publication No. 2022 / 0071984 to Poole et al.; U.S. Patent Application Publication No. 2021 / 0378948 to Gerardi et al.; U.S. Patent Application Publication No. 2021 / 0330590 to Hutchens et al.; U.S. Patent Application Publication No. 2021 / 0186081 to Gerardi et al.; U.S. Patent Application Publication No. 2021 / 0177754 to Keller et al.; U.S. Patent Application Publication No. 2021 / 0186081 to Gerardi et al.; U.S. Patent Application Publication No. 2021 / 0177754 to Gerardi et al., each of which is incorporated herein by reference. See, for example, U.S. Patent Application Publication No. 1 / 0177043 to Gerardi et al.; U.S. Patent Application Publication No. 2021 / 0177038 to Holton, Jr. et al.; U.S. Patent Application Publication No. 2021 / 0169867 to Holton, Jr. et al.; U.S. Patent Application Publication No. 2021 / 0169792 to Holton, Jr. et al.; U.S. Patent Application Publication No. 2021 / 0169132 to Holton, Jr. et al.; U.S. Patent Application Publication No. 2021 / 0169121 to St. Charles, and U.S. Patent Application Publication No. 2021 / 0169122 to St. Charles. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] U.S. Pat. No. 5,387,416 [Patent Document 2] U.S. Patent No. 6,668,839 [Patent Document 3] U.S. Patent No. 6,834,654 [Patent Document 4] U.S. Patent No. 6,953,040 [Patent Document 5] U.S. Patent No. 7,032,601 [Patent Document 6] U.S. Patent No. 7,694,686 [Patent Document 7] U.S. Patent No. 7,810,507 [Patent Document 8] U.S. Pat. No. 7,819,124 [Patent Document 9] U.S. Pat. No. 7,861,728 [Patent Document 10] U.S. Pat. No. 7,901,512 [Patent Document 11] U.S. Pat. No. 8,627,828 [Patent Document 12] U.S. Pat. No. 11,246,334 [Patent Document 13] US Patent Application Publication No. 2008 / 0196730 [Patent Document 14] US Patent Application Publication No. 2008 / 0305216 [Patent Document 15] US Patent Application Publication No. 2009 / 0293889 [Patent Document 16] US Patent Application Publication No. 2010 / 0291245 [Patent Document 17] US Patent Application Publication No. 2011 / 0139164 [Patent Document 18] US Patent Application Publication No. 2012 / 0037175 [Patent Document 19] US Patent Application Publication No. 2012 / 0055494 [Patent Document 20] US Patent Application Publication No. 2012 / 0138073 [Patent Document 21] US Patent Application Publication No. 2012 / 0138074 [Patent Document 22] US Patent Application Publication No. 2013 / 0074855 [Patent Document 23] US Patent Application Publication No. 2013 / 0074856 [Patent Document 24] US Patent Application Publication No. 2013 / 0152953 [Patent Document 25] US Patent Application Publication No. 2013 / 0274296 [Patent Document 26] US Patent Application Publication No. 2015 / 0068545 [Patent Document 27] US Patent Application Publication No. 2015 / 0101627 [Patent Document 28] US Patent Application Publication No. 2015 / 0230515 [Patent Document 29] US Patent Application Publication No. 2022 / 0160675 [Patent Document 30] US Patent Application Publication No. 2022 / 0071984 [Patent Document 31] US Patent Application Publication No. 2021 / 0378948 [Patent Document 32] US Patent Application Publication No. 2021 / 0330590 [Patent Document 33] US Patent Application Publication No. 2021 / 0186081 [Patent Document 34] US Patent Application Publication No. 2021 / 0177754 [Patent Document 35] US Patent Application Publication No. 2021 / 0177043 [Patent Document 36] US Patent Application Publication No. 2021 / 0177038 [Patent Document 37] US Patent Application Publication No. 2021 / 0169867 [Patent Document 38] US Patent Application Publication No. 2021 / 0169792 [Patent Document 39] US Patent Application Publication No. 2021 / 0169132 [Patent Document 40] US Patent Application Publication No. 2021 / 0169121 [Patent Document 41] US Patent Application Publication No. 2021 / 0169122 Summary of the Invention [Means for solving the problem]

[0006] (Brief summary) The present disclosure relates to products incorporating a nicotine component in the form of a nicotine polymer complex. In some embodiments, the product comprises two or more different nicotine components (including at least one such component in the form of a nicotine polymer complex). Without intending to be limited by theory, it is believed that the nicotine release profile in the oral cavity of a consumer can be modified (e.g., extended) by incorporating nicotine in the form of a nicotine polymer complex (and / or by incorporating nicotine in the form of two or more different nicotine components in a single product) compared to the nicotine release profile of a product that comprises other forms of nicotine or only one form of nicotine, respectively. In some embodiments, the inclusion of nicotine in the form of a nicotine polymer complex and / or as two or more nicotine components in a single product can further improve the shelf life of the product. Some such products are pouch products that include an outer water-permeable pouch that defines a cavity that contains a composition that comprises a water-soluble component that is releasable through the water-permeable pouch.

[0007] The composition in the cavity of the pouch may contain a nicotine component including nicotine in the form of a nicotine complex (e.g., a nicotine polymer complex, e.g., where the polymer comprises a polymeric cation exchange resin). The composition in the cavity of the pouch may contain nicotine in the form of a nicotine polymer complex as a first nicotine component and may further include a second, different nicotine component (e.g., in the form of a nicotine extract, e.g., in the form of a tobacco-derived nicotine extract or a synthetic nicotine) and / or a nicotine salt. The composition in the cavity may further include various components including, but not limited to, flavoring agents, sweeteners, fillers, and the like. In some embodiments, the composition in the cavity may further include an alkali metal or alkaline earth metal salt, e.g., including calcium or magnesium. In some embodiments, the composition in the cavity may further include other salts.

[0008] In some embodiments, at least a portion of the alkali metal or alkaline earth metal salt is a salt of an organic acid. In some embodiments, the composition comprises a calcium salt of an organic acid. In some embodiments, the calcium salt is calcium benzoate, calcium gluconate, calcium glycerol phosphate, calcium lactate, calcium lactate gluconate, or a combination thereof. In some embodiments, the calcium salt is calcium lactate gluconate. In some embodiments, the calcium salt is calcium benzoate. In some embodiments, the calcium benzoate is present as a separate calcium benzoate. In other embodiments, the composition comprises benzoic acid and calcium hydroxide, and the calcium benzoate is formed in situ in the composition during its preparation and / or use.

[0009] In some embodiments, the composition comprises benzoic acid, sodium benzoate, calcium benzoate, or a combination thereof, and further comprises an additional alkali metal salt, an alkaline earth metal salt, or a combination thereof. In some embodiments, the additional alkaline earth metal salt comprises calcium. In some embodiments, the additional alkaline earth metal salt comprises calcium and an additional organic acid. In some embodiments, the additional alkaline earth metal salt comprises lactic acid, gluconic acid, glycerophosphate, or a combination thereof. In some embodiments, the composition comprises calcium gluconate, calcium glycerol phosphate, calcium lactate, calcium lactate gluconate, or a combination thereof. In some embodiments, the composition comprises calcium lactate gluconate.

[0010] In some embodiments, at least a portion of the alkali metal salt of the organic acid, the alkaline earth metal salt of the organic acid, or both, if present, is bound to at least a portion of the nicotine polymer conjugate in the form of a salt, an ion pair, or a combination thereof.

[0011] In some embodiments, when a sample of the composition is added to a volume of water and agitated using a rotary shaker at 250 RPM for 2 hours and at a temperature of 37° C., at least about 40%, or at least about 60%, of the nicotine present in the form of a nicotine polymer complex is released from the composition to form a solution containing nicotine. In some embodiments, the solution has a pH of about 5.0 to about 6.5. In some embodiments, the solution has a LogD greater than zero.

[0012] In various embodiments, the composition in the cavity of the pouch is a smokeless tobacco product or a nicotine replacement therapy product. In some embodiments, the composition in the cavity of the pouch can be a particulate material adapted for steeping or brewing (i.e., designed for liquid extraction), such as tea or coffee material. Thus, in certain embodiments, the composition in the cavity of the pouch can include particulate or fibrous plant material found, for example, in various teas or tea varieties. In some embodiments, the composition in the cavity can include flavoring ingredients so that flavors can be added to a liquid (e.g., water).

[0013] The present invention includes, without limitation, the following embodiments.

[0014] Embodiment 1: A pouch product comprising an outer water-permeable pouch defining a cavity and a composition adapted for oral use located within the cavity, the pouch product having a total moisture content of about 5% or greater, the composition comprising a nicotine component in the form of a nicotine polymer complex.

[0015] Embodiment 2: The pouch product of embodiment 1, wherein the nicotine component is the only nicotine component contained within the composition.

[0016] Embodiment 3: The pouch product of embodiment 1, wherein the nicotine component is a first nicotine component and the composition further comprises a second nicotine component selected from the group consisting of nicotine and a nicotine salt.

[0017] Embodiment 4: A pouch product according to any one of embodiments 1 to 3, wherein the total moisture content of the pouch product is about 5% or more, about 10% or more, about 15% or more, about 25% or more, or about 30% or more.

[0018] Embodiment 5: A pouch product according to any one of embodiments 1 to 4, having a total moisture content of about 48% or less, about 40% or less, about 30% or less, about 25% or less, about 20% or less, about 15% or less, or about 10% or less.

[0019] Embodiment 6: A pouch product according to any of embodiments 3 to 5, wherein the first nicotine component is provided in an amount of about 2% to about 15% by weight, and the second nicotine component is provided in an amount of about 0.5% to about 2% by weight, based on the total weight of the composition.

[0020] Embodiment 7: A pouch product according to any of embodiments 3-5, wherein the nicotine provided by the first nicotine component is present in a higher weight percentage than the nicotine provided by the second nicotine component.

[0021] Embodiment 8: A pouch product according to any of embodiments 3-5, wherein the nicotine provided by the first nicotine component is present in a lower weight percentage than the nicotine provided by the second nicotine component.

[0022] Embodiment 9: The pouch product of any of embodiments 1-8, wherein the nicotine polymer complex comprises a polymeric cation exchange resin.

[0023] Embodiment 10: The pouch product of embodiment 9, wherein the polymeric cation exchange resin comprises a polyacrylic polymer.

[0024] Embodiment 11: The pouch product of embodiment 9, wherein the nicotine polymer complex comprises nicotine polacrilex.

[0025] Embodiment 12: The pouch product of any of embodiments 3-11, wherein the second nicotine component is a tobacco-derived nicotine extract.

[0026] Embodiment 13: A pouch product according to any of embodiments 3-11, wherein the second nicotine component is a synthetic nicotine.

[0027] Embodiment 14: The pouch product of any of embodiments 3-11, wherein the second nicotine component is a nicotine salt.

[0028] Embodiment 15: A pouch product according to any of embodiments 3 to 14, wherein at least a portion of the second nicotine component is in the form of a particulate non-tobacco material that has been processed to contain the second nicotine component and a fibrous plant material that retains the second nicotine component.

[0029] Embodiment 16: The pouch product of any one of embodiments 1 to 15, wherein the composition comprises one or more components selected from the group consisting of one or more additional fillers, binders, pH adjusters, colorants, disintegration aids, antioxidants, moisturizers, and preservatives.

[0030] Embodiment 17: The pouch product of embodiment 16, wherein the composition comprises a pH adjuster selected from sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, and combinations thereof.

[0031] Embodiment 18: The pouch product of embodiment 17, wherein the composition comprises calcium hydroxide.

[0032] Embodiment 19: The pouch product of any of embodiments 1 to 18, wherein the composition has a pH of about 6 to 9.

[0033] Embodiment 20: The pouch product of any of embodiments 1-18, wherein the composition has a pH of less than about 6.5.

[0034] Embodiment 21: The pouch product of any of embodiments 1-18, wherein the composition has a pH of less than about 5.

[0035] Embodiment 22: A pouch product according to any one of embodiments 1 to 21, wherein the composition comprises about 5% or more of a moisturizer.

[0036] Embodiment 23: The pouch product of embodiment 22, wherein the humectant comprises glycerol.

[0037] Embodiment 24: The pouch product of any of embodiments 1-23, further comprising one or more alkali metal salts, one or more alkaline earth metal salts, or any combination thereof.

[0038] Embodiment 25: The pouch product of embodiment 24, wherein the one or more alkali metal salts and / or the one or more alkaline earth metal salts are salts of an organic acid.

[0039] Embodiment 26: The pouch product of embodiment 25, wherein the one or more alkali metal salts and / or the one or more alkaline earth metal salts comprise a calcium salt and / or a magnesium salt.

[0040] Embodiment 27: The pouch product of embodiment 25, wherein the one or more alkali metal salts and / or the one or more alkaline earth metal salts comprise a calcium salt.

[0041] Embodiment 28: The pouch product of embodiment 27, wherein the calcium salt is selected from the group consisting of calcium benzoate, calcium gluconate, calcium glycerol phosphate, calcium lactate, calcium lactate gluconate, and any combination thereof.

[0042] Embodiment 29: The pouch product of embodiment 28, wherein the calcium salt is calcium lactate gluconate.

[0043] Embodiment 30: The pouch product of embodiment 28, wherein the calcium salt is calcium benzoate.

[0044] Embodiment 31: The pouch product of embodiment 30, wherein the calcium benzoate is present as a separate calcium benzoate.

[0045] Embodiment 32: The pouch product of embodiment 30, wherein during its preparation and / or use, calcium benzoate is formed in situ by calcium hydroxide and benzoic acid present in the composition.

[0046] Embodiment 33: A pouch product described in any of embodiments 24 to 32, wherein at least a portion of the one or more alkali metal salts of one or more organic acids, one or more alkaline earth metal salts of one or more organic acids, or any combination thereof, is associated with at least a portion of the nicotine component in the form of an ion pair.

[0047] Embodiment 34: A pouch product according to any of embodiments 1 to 33, wherein the nicotine polymer complex is present in the form of particles.

[0048] Embodiment 35: The pouch product of embodiment 34, wherein the particles have an average particle size of about 25 microns to about 500 microns.

[0049] Embodiment 36: The pouch product of embodiment 35, wherein the particles have an average particle size of about 200 microns to about 400 microns.

[0050] Embodiment 37: A pouch product according to any of embodiments 34 to 36, wherein less than 2% by volume of the particles, or less than 1% by volume of the particles have a particle size of less than about 5 microns.

[0051] Embodiment 38: A pouch product according to any of embodiments 34 to 37, wherein less than 2% by volume of the particles or less than 1% by volume of the particles have a particle size greater than about 1000 microns.

[0052] Embodiment 39: A pouch product according to any one of embodiments 34 to 38, wherein the particles exhibit a multimodal particle size distribution.

[0053] Embodiment 40: The pouch product of embodiment 39, wherein the particles exhibit a bimodal particle size distribution.

[0054] Embodiment 41: The pouch product of embodiment 40, wherein the bimodal particle size distribution comprises a first mode having a peak at about 75 to about 125 micrometers or about 80 to about 110 micrometers and a second mode having a peak at about 500 to about 1000 micrometers or about 700 to about 1000 micrometers.

[0055] Embodiment 42: The pouch product of embodiment 41, wherein more particles are present in the first mode than in the second mode.

[0056] Embodiment 43: A pouch product according to any one of embodiments 34 to 42, wherein the particles are uncoated.

[0057] Embodiment 44: A pouch product according to any of embodiments 34 to 42, wherein the particles are coated with a coating comprising one or more fill ingredients and / or one or more pH adjusters.

[0058] Embodiment 45: The pouch product of embodiment 44, wherein the one or more fill ingredients comprise mannitol and the one or more pH adjusters comprise sodium carbonate.

[0059] Embodiment 46: A pouch product described in any one of embodiments 1 to 45, wherein the pouch product has a total moisture content of about 48% or less, a total moisture content of about 40% or less, a total moisture content of about 30% or less, or a total moisture content of about 20% or less.

[0060] Embodiment 47: A pouch product according to any one of embodiments 1 to 45, wherein the pouch product has a total moisture content of about 1% to about 40%, about 1% to about 30%, about 1% to about 20%, or about 1% to about 10%.

[0061] Embodiment 48: A composition comprising a first nicotine component in the form of a nicotine polymer complex and a second nicotine component selected from the group consisting of nicotine and nicotine salts, wherein the composition is in the form of a pouch product.

[0062] Embodiment 49: The composition of embodiment 48, wherein the first nicotine component is provided in an amount of about 2% to about 15% by weight, and the second nicotine component is provided in an amount of about 0.5% to about 2% by weight, based on the total weight of the composition.

[0063] Embodiment 50: The composition of embodiment 48 or 49, wherein the nicotine provided by the first nicotine component is present in a higher weight percentage than the nicotine provided by the second nicotine component.

[0064] Embodiment 51: The composition of embodiment 48 or 49, wherein the nicotine provided by the first nicotine component is present in a lower weight percentage than the nicotine provided by the second nicotine component.

[0065] Embodiment 52: The composition of any of embodiments 48-51, wherein the nicotine polymer complex comprises a polymeric cation exchange resin.

[0066] Embodiment 53: The composition of embodiment 52, wherein the polymeric cation exchange resin comprises a polyacrylic polymer.

[0067] Embodiment 54: The composition of embodiment 52, wherein the nicotine polymer conjugate comprises nicotine polacrilex.

[0068] Embodiment 55: The composition of any of embodiments 48-54, wherein the second nicotine component is a nicotine extract derived from tobacco.

[0069] Embodiment 56: The composition of any of embodiments 48-54, wherein the second nicotine component is a synthetic nicotine.

[0070] Embodiment 57: The composition of any of embodiments 48-54, wherein the second nicotine component is a nicotine salt.

[0071] Embodiment 58: A composition according to any of embodiments 48 to 57, wherein at least a portion of the second nicotine component is in the form of a particulate non-tobacco material that has been processed to contain the second nicotine component and a fibrous plant material that retains the second nicotine component.

[0072] Embodiment 59: The composition of any one of embodiments 48 to 58, comprising one or more components selected from the group consisting of one or more additional fillers, binders, pH adjusters, colorants, disintegration aids, antioxidants, moisturizers, and preservatives.

[0073] Embodiment 60: The composition of embodiment 59, comprising a pH adjuster selected from sodium hydroxide, potassium hydroxide, calcium hydroxide, and combinations thereof.

[0074] Embodiment 61: The composition of embodiment 60, comprising calcium hydroxide.

[0075] Embodiment 62: A composition described in any of embodiments 48 to 61, having a pH of about 7 to 9.

[0076] Embodiment 63: The composition of any of embodiments 48 to 61, having a pH of less than about 6.5.

[0077] Embodiment 64: The composition of any of embodiments 48 to 61, having a pH of less than about 5.

[0078] Embodiment 65: The composition of any one of embodiments 48-64, comprising about 5% or more of a moisturizer.

[0079] Embodiment 66: The composition of embodiment 65, wherein the moisturizer comprises glycerol.

[0080] Embodiment 67: The composition of any of embodiments 48-66, further comprising one or more alkali metal salts, one or more alkaline earth metal salts, or any combination thereof.

[0081] Embodiment 68: The composition of embodiment 67, wherein the one or more alkali metal salts and / or the one or more alkaline earth metal salts are salts of an organic acid.

[0082] Embodiment 69: The composition of embodiment 67 or 68, wherein the one or more alkali metal salts and / or the one or more alkaline earth metal salts comprise a calcium salt and / or a magnesium salt.

[0083] Embodiment 70: The composition of embodiment 69, wherein the one or more alkali metal salts and / or the one or more alkaline earth metal salts comprise a calcium salt.

[0084] Embodiment 71: The composition of embodiment 70, wherein the calcium salt is selected from the group consisting of calcium benzoate, calcium gluconate, calcium glycerol phosphate, calcium lactate, calcium lactate gluconate, and any combination thereof.

[0085] Embodiment 72: The composition of embodiment 70, wherein the calcium salt is calcium lactate gluconate.

[0086] Embodiment 73: The composition of embodiment 70, wherein the calcium salt is calcium benzoate.

[0087] Embodiment 74: The composition of embodiment 73, wherein the calcium benzoate is present as a separate calcium benzoate.

[0088] Embodiment 75: The composition of embodiment 73, wherein during its preparation and / or use, calcium benzoate is formed in situ by calcium hydroxide and benzoic acid present in the composition.

[0089] Embodiment 76: A composition described in any of embodiments 67 to 75, wherein at least a portion of the one or more alkali metal salts, one or more alkaline earth metal salts, or any combination thereof, is associated with at least a portion of the nicotine component in the form of an ion pair.

[0090] Embodiment 77: A composition described in any of embodiments 48 to 76, wherein the nicotine polymer complex is present in the form of particles.

[0091] Embodiment 78: The composition of embodiment 77, wherein the particles have an average particle size of about 25 microns to about 500 microns.

[0092] Embodiment 79: The composition of embodiment 77, wherein the particles have an average particle size of about 200 microns to about 400 microns. Embodiment 80: The composition of any of embodiments 77-79, wherein less than 2% by volume of the particles, or less than 1% by volume of the particles have a particle size less than about 5 microns.

[0093] Embodiment 81: The composition of any of embodiments 77-79, wherein less than 2% by volume of the particles or less than 1% by volume of the particles have a particle size greater than about 1000 microns.

[0094] Embodiment 82: The composition of any of embodiments 77 to 81, wherein the particles exhibit a multimodal particle size distribution.

[0095] Embodiment 83: The composition of embodiment 82, wherein the particles exhibit a bimodal particle size distribution.

[0096] Embodiment 84: The composition of embodiment 83, wherein the bimodal particle size distribution comprises a first mode having a peak at about 75 to about 125 micrometers or about 80 to about 110 micrometers and a second mode having a peak at about 500 to about 1000 micrometers or about 700 to about 1000 micrometers.

[0097] Embodiment 85: The composition of embodiment 84, wherein more particles are present in the first mode than in the second mode.

[0098] Embodiment 86: The composition of any one of embodiments 77 to 85, wherein the particles are not coated.

[0099] Embodiment 87: A composition described in any of embodiments 77 to 85, wherein the particles are coated with a coating comprising one or more loading ingredients and / or one or more pH adjusters.

[0100] Embodiment 88: The composition of embodiment 87, wherein the one or more fill ingredients comprise mannitol and the one or more pH adjusters comprise sodium carbonate.

[0101] Embodiment 89: The composition of any of embodiments 48-88, having a total moisture content of about 40% or less, a total moisture content of about 30% or less, or a total moisture content of about 20% or less.

[0102] Embodiment 90: The composition of any of embodiments 48-88, having a total water content of from about 1% to about 40%, from about 1% to about 30%, from about 1% to about 20%, or from about 1% to about 10%.

[0103] Embodiment 91: A method of providing a pouch product having a modified nicotine release profile comprising an outer water-permeable pouch defining a cavity and a composition adapted for oral use located within the cavity, the method comprising incorporating nicotine in the form of a nicotine-polymer complex, and incorporating water within the pouch product and / or adding water to the pouch product to obtain a moist pouch product having a total moisture content of about 5% or more.

[0104] Embodiment 92: A method of providing a moist pouch product having a modified nicotine release profile comprising an outer water-permeable pouch defining a cavity and a composition adapted for oral use located within the cavity, the method comprising incorporating nicotine in the form of a nicotine-polymer complex, and incorporating water within the pouch product and / or adding water to the pouch product to obtain a moist pouch product having a total moisture content of about 25% or more.

[0105] Embodiment 93: A method of providing a pouch product having a modified nicotine release profile comprising an outer water-permeable pouch defining a cavity and a composition adapted for oral use located within the cavity, the method comprising incorporating nicotine in the form of two or more different nicotine components comprising: a first nicotine component in the form of a nicotine polymer complex; and a second nicotine component selected from the group consisting of nicotine and a nicotine salt, and incorporating water within the pouch product and / or adding water to the pouch product, thereby obtaining a moist pouch product having a total moisture content of about 5% or more.

[0106] Embodiment 94: A method of providing a moist pouch product having a modified nicotine release profile comprising an outer water-permeable pouch defining a cavity and a composition adapted for oral use located within the cavity, the method comprising incorporating nicotine in the form of two or more different nicotine components comprising a first nicotine component in the form of a nicotine polymer complex; and a second nicotine component selected from the group consisting of nicotine and a nicotine salt, and incorporating water within the pouch product and / or adding water to the pouch product, thereby obtaining a moist pouch product having a total moisture content of about 25% or more.

[0107] These and other features, aspects and advantages of the present disclosure will become apparent upon reading the following detailed description in conjunction with the accompanying figures, which are briefly described below. The present invention includes any combination of two, three, four or more of the above-described embodiments, as well as any combination of two, three, four or more features or elements described in this disclosure, regardless of whether such features or elements are explicitly combined in the description of a particular embodiment herein. Because this disclosure is intended to be read as a whole, it should be considered that any separable features or elements of the disclosed invention are intended to be combinable in any of its various aspects and embodiments, unless the context clearly dictates otherwise.

[0108] Having thus described aspects of the present disclosure in the foregoing general paragraphs, reference is now made to the accompanying drawings, which are not necessarily drawn to scale, and which are illustrative only and should not be construed as limiting the disclosure. [Brief description of the drawings]

[0109] [Figure 1] 1 is a front perspective view illustrating a pouch product according to an embodiment of the present disclosure; [Diagram 2] 1 is a graphical depiction of % nicotine release versus pH for resin bound nicotine in combination with sodium hydroxide and calcium hydroxide, according to an exemplary embodiment of the present disclosure; [Diagram 3] 1 is a graphical depiction of % nicotine release versus ionic strength for resin bound nicotine in combination with various sodium and calcium salts according to an exemplary embodiment of the present disclosure; [Figure 4] 1 is a graphical depiction of nicotine release % versus ionic strength for resin-bound nicotine in combination with various salts and salt combinations according to an exemplary embodiment of the present disclosure; and [Diagram 5] 1 is a graphical depiction of nicotine % and pH values ​​for resin bound nicotine in combination with various salts and pouch products according to an exemplary embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0110] The present invention will now be described more fully hereinafter. However, the present invention may be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. As used in this specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0111] The compositions and products of the present disclosure generally include a nicotine polymer complex. In some embodiments, the nicotine polymer complex is the only source of nicotine in the compositions and products. In some embodiments, the compositions and products include at least two different nicotine components (including nicotine polymer complexes). It is noted that the present disclosure is not intended to be so limited, and in some embodiments, such compositions and products can include more than two different nicotine components (e.g., three, four, or more different nicotine components), including nicotine polymer complexes.

[0112] The present disclosure generally provides compositions and products that are structured for oral use. The term "structured for oral use" as used herein means that the product is provided in a form such that one or more components of the mixture (e.g., flavoring agent and / or nicotine) are carried into the user's mouth by the user's oral saliva during use. In certain embodiments, the product is adapted to deliver a component to the user via the user's oral mucosa, the user's digestive system, or both, and in some cases, the component is an active ingredient (including, but not limited to, for example, nicotine) that can be absorbed via the oral mucosa or absorbed via the digestive tract when the product is used. Certain compositions or products of the present disclosure may be dissolvable. As used herein, the terms "dissolve", "dissolving" and "dissolvable" refer to a composition that has water-soluble components that interact with moisture in the oral cavity and go into solution, thereby causing slow consumption of the composition. According to one aspect, a dissolvable composition is capable of persisting in the user's mouth for a given period of time until it is completely dissolved. The dissolution rate can vary over a wide range, from about 1 minute or less to about 60 minutes. For example, a fast release composition usually dissolves and / or releases the desired component(s) (e.g., active ingredient, flavor, etc.) in about 2 minutes or less, often about 1 minute or less (e.g., about 50 seconds or less, about 40 seconds or less, about 30 seconds or less, or about 20 seconds or less). Dissolution can occur by any means, such as melting, mechanical destruction (e.g., chewing), enzymatic or other chemical degradation, or by disruption of interactions between the components of the composition. In other embodiments, the product does not dissolve during the product's residence in the user's mouth.

[0113] In some embodiments, the present disclosure provides products in the form of a mixture of one or more components (including the nicotine polymer complexes further described herein) disposed within a moisture-permeable container (e.g., a moisture-permeable pouch). The pouch products generally include an intra-pouch mixture that typically includes, in addition to an exterior pouch base, one or more fillers, one or more flavorings, and various other optional ingredients (in addition to the two or more different nicotine components described herein). The composition of the intra-pouch material provided herein is not particularly limited and can include any fill composition, including those included within conventional pouch products, in addition to the nicotine polymer complexes (alone or in combination with one or more different nicotine sources). Such compositions are generally mixtures of two or more components, and thus the compositions are, in some cases, referred to hereinafter as "mixtures". Certain components that can be advantageously included in the mixtures within certain embodiments of the pouches provided herein are generally outlined below. However, it should be understood that this discussion is not intended to limit the components that can be incorporated within the disclosed pouches.

[0114] Such mixtures in water-permeable pouch format are typically used by placing the pouch containing the mixture in the mouth of a human subject / user. Typically, the pouch is placed in the user's oral cavity, e.g., somewhere under the lips, in the same manner as moist snuff products are typically used. The pouch is preferably not chewed or swallowed. Exposure to saliva then allows some of the components in the mixture (e.g., flavorings and / or nicotine) to pass through, e.g., the water-permeable pouch, providing flavor and satisfaction to the user without the user having to expectorate any part of the mixture. After about 10 minutes to about 60 minutes, typically about 15 minutes to about 45 minutes of use / enjoyment, a substantial amount of the mixture is ingested by the human subject and the pouch can be removed from the consumer's mouth for disposal. Preferred pouch materials for the products described herein can be designed and manufactured such that under normal conditions of use, a significant amount of the contents of the formulation within the pouch will permeate through the pouch material before the pouch loses its physical integrity.

[0115] For example, as illustrated in Figure 1, an exemplary pouch product 10 can include an outer water-permeable container 20 in the form of a pouch containing a granular mixture 15 adapted for oral use, where the granular mixture 15 includes a nicotine polymer complex as described herein. The orientation, size, and type of the outer water-permeable pouch and the type and nature of the composition adapted for oral use as illustrated herein are not to be construed as being limiting. Certain specific examples of components incorporated into the granular mixture 15 are described herein below, followed by a disclosure regarding suitable outer water-permeable containers 20 forming the pouch product 10.

[0116] Nicotine content As referred to herein above, compositions and products are provided herein that contain at least one nicotine component in the form of a nicotine polymer complex.In some such compositions and products, the nicotine polymer complex is the only nicotine component in the composition and / or product.In other embodiments, the nicotine polymer complex is included in the composition or product together with one or more other types of nicotine components.

[0117] "Nicotine component" refers to any suitable form of nicotine (e.g., free base or salt) to provide oral absorption of at least a portion of the nicotine present. Various nicotinic acid compounds and methods for their administration are described in U.S. Patent Publication No. 2011 / 0274628 to Borschke, which is incorporated herein by reference. As used herein, "nicotinic acid compound" often refers to a naturally occurring or synthetic nicotinic acid compound that is not bound to plant material, meaning that the compound is at least partially purified and is not contained within a plant structure, such as tobacco leaves.

[0118] In some embodiments, the nicotine is naturally derived and obtained as an extract from Nicotiana species (e.g., tobacco). The nicotine can be, for example, in the form of a highly refined tobacco extract. Various methods are known for the isolation and purification of nicotine from tobacco, including, but not limited to, extraction from tobacco with water; extraction from tobacco with organic solvents; steam distillation from tobacco; or pyrolysis of tobacco and distillation of nicotine therefrom. For exemplary extraction methods, see, for example, U.S. Pat. Nos. 2,822,306 and 4,153,063 to Roselius et al. and U.S. Patent Application Publication No. 2008 / 0302377 to Kauryzbaev et al., which are incorporated herein by reference. In some embodiments, the nicotine can also be obtained from another source (e.g., another type of plant).

[0119] In some embodiments, nicotine can be synthetically produced. The method by which the synthetic nicotine used in some embodiments of the compositions and products described herein is synthesized may vary and is not particularly limited. Various methods for the preparation of nicotine are known. See, for example, Florence L.Wagner et al., 63 Tetrahedron 8065 (2007); McCague et al., U.S. Pat. No. 10,913,962; and Weber et al., U.S. Patent Application Publication No. 2020 / 0331884, which are incorporated herein by reference in their entirety.

[0120] Nicotine can have the enantiomeric forms S(-)-nicotine, R(+)-nicotine, or a mixture of S(-)-nicotine and R(+)-nicotine. Most preferably, the nicotine is in the form of S(-)-nicotine (e.g., a form that is substantially all S(-)-nicotine) or a racemic mixture composed primarily or predominantly of S(-)-nicotine (e.g., a mixture composed of about 95 parts by weight of S(-)-nicotine and about 5 parts by weight of R(+)-nicotine). Most preferably, the nicotine is utilized in a substantially pure form or in an essentially pure form. Highly preferred nicotine utilized has a purity of greater than about 95 percent, more preferably greater than about 98 percent, and most preferably greater than about 99 percent, on a weight basis.

[0121] As mentioned, compositions and products according to the present disclosure generally include at least one nicotine component that is a nicotine polymer complex. Such complexes, in certain embodiments, include a polymeric resin (e.g., a polymeric ion exchange resin, e.g., a polymeric cation exchange resin) to which nicotine is bound. One example of such a resin is polymethacrylic acid, such as Amberlite IRP64, Purolite C115HMR, or Doshion P551. See, for example, U.S. Patent No. 3,901,248 to Lichtneckert et al., which is incorporated herein by reference. Another example is a nicotine-polyacrylcarbomer complex, such as Carbopol 974P. In some embodiments, nicotine may be present in the form of a nicotine polyacryl complex. One example of a suitable nicotine polymer complex is nicotine polacrilex, which includes nicotine bound to a resin prepared from methacrylic acid and divinylbenzene. Nicotine polacrilex is available in different nicotine percentages, such as 18% to 20% nicotine. Without being limited thereto, nicotine polacrilex generally contains 95% or more of the labeled amount of nicotine when calculated on an anhydrous basis. In some embodiments, the inclusion of a nicotine component in the form of a nicotine polymer complex can result in improved shelf-life stability and better / slower release from the nicotine composition / product. In some embodiments, the inclusion of a nicotine component in the form of a nicotine polymer complex can result in less burning sensation in the oral cavity during use. The amount of nicotine provided by the nicotine polymer complex can vary from about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, or about 60% to about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or 100% based on the total weight of nicotine provided by all nicotine components in a given composition.Certain non-limiting exemplary amounts of nicotine polymer complex (including resin and nicotine) incorporated within a given composition can range, for example, from about 0.5% to about 15% by weight, for example, from about 1% to about 10% by weight, for example, from about 2% to about 5% by weight, based on the total weight of the composition / mixture to be included within the pouch product.

[0122] In some embodiments, the particle size of the nicotine polymer complex may be purposefully selected. For example, in some embodiments, it may be desirable to provide compositions and products having nicotine polymer complexes with a specified average particle size and / or a specified particle size distribution. The values ​​provided below as exemplary embodiments of particle size and distribution of nicotine polymer complexes are based on sieving and / or light scattering measurements, which are generally known in the art for evaluating particle size. For example, size distribution measurements can be based on mesh size using a RO-TAP® sieve shaker, as described, for example, at hub.wstyler.com / rotap-guide (last accessed 8-22-2022), which is incorporated herein by reference in its entirety.

[0123] In various embodiments, the nicotine polymer complexes in the disclosed compositions and products have an average particle size of at least about 1 micrometer, at least about 5 micrometers, at least about 10 micrometers, at least about 25 micrometers, at least about 50 micrometers, at least about 100 micrometers, at least about 150 micrometers, at least about 200 micrometers, at least about 250 micrometers, at least about 300 micrometers, at least about 350 micrometers, at least about 400 micrometers, or at least about 450 micrometers. In various embodiments, the nicotine polymer complexes in the disclosed compositions and products have an average particle size of less than about 800 micrometers, less than about 750 micrometers, less than about 700 micrometers, less than about 650 micrometers, less than about 600 micrometers, less than about 550 micrometers, less than about 500 micrometers, less than about 450 micrometers, less than about 400 micrometers, less than about 350 micrometers, less than about 300 micrometers, less than about 250 micrometers, less than about 200 micrometers, less than about 150 micrometers, less than about 100 micrometers, less than about 50 micrometers, or less than about 25 micrometers.

[0124] In some embodiments, the average particle size is from about 25 microns to about 500 microns, e.g., from about 50 microns to about 500 microns, from about 100 microns to about 300 microns, from about 100 microns to about 250 microns, from about 200 microns to about 300 microns, or from about 200 microns to about 250 microns.

[0125] In some embodiments, the minimum particle size is about 0.1 microns or more, for example, about 0.2 microns or more. In some embodiments, any particles having a size smaller than about 5 microns are present in a volume percentage of less than 1%, less than 0.5%, less than 0.25%, or less than 0.1% based on the total amount of nicotine polymer complex particles. In some embodiments, the maximum particle size is about 5000 microns or less. In some embodiments, any particles having a size larger than 1000 microns are present in a volume percentage of less than 1.2%, less than 1.1%, or less than 1%.

[0126] In certain embodiments, the particle size of the nicotine polymer complex particles exhibits a multimodal, e.g., bimodal, distribution. In some embodiments, the particles exhibit a first mode having a peak at about 75 to 125 micrometers, e.g., about 80 to about 110 micrometers, and a second mode having a peak at about 500 to 1000 micrometers, e.g., about 700 to about 1000 micrometers. In preferred embodiments, the first mode is the predominant mode.

[0127] In some embodiments, the nicotine polymer complex particles are utilized as uncoated particles (consisting essentially of nicotine polymer complex). In other embodiments, the nicotine polymer complex particles are partially or completely coated / encapsulated with one or more coatings and / or outer shells. For example, in certain embodiments, the nicotine polymer complex particles are encapsulated with one or more polyols and one or more pH modifiers. In one particular embodiment, nicotine polymer complex particles are provided that are coated or encapsulated with a combination of mannitol and sodium carbonate. Certain such encapsulated nicotine polymer complex particles can have an average particle size of about 350 microns to about 500 microns.

[0128] The nicotine polymer complex can be used alone or in combination with one or more additional nicotine components. In some embodiments, the nicotine polymer complex is the only nicotine source in a given composition or product. In some embodiments, the nicotine polymer complex is one of two (or more) nicotine sources in a given composition or product. In certain such embodiments, the nicotine polymer complex is referred to as the "first nicotine component" and the composition / product further comprises one or more additional nicotine components (e.g., a "second nicotine component"), which is different from the first nicotine component.

[0129] In some embodiments, the second (and / or, optionally, third, fourth, fifth, etc.) nicotine component is selected from the group consisting of unbound nicotine in the form of nicotine free base or nicotine salt. By "unbound nicotine" it is meant that nicotine is not intentionally added to the composition in the form of nicotine bound in a resin. The nicotine free base or nicotine salt can be utilized alone, i.e., in the form of an extract or other purified material. In some embodiments, the nicotine free base or nicotine salt can be adsorbed, for example, onto a microcrystalline cellulose material to form a microcrystalline cellulose-nicotine carrier complex.

[0130] This second nicotine component can be, for example, nicotine in its free base form. See, for example, the discussion of nicotine in free base form in Hansson's US Patent Publication No. 2004 / 0191322, which is incorporated herein by reference. The second nicotine component can alternatively be, for example, nicotine in the form of a salt, for example, a salt with one or more organic acids. Nicotine salts can be provided using the types of ingredients and techniques described in U.S. Patent No. 2,033,909 to Cox et al. and Perfetti, Beitrage Tabakforschung Int., vol. 12:43-54 (1983), which are incorporated herein by reference. Additionally, nicotine salts are available from sources such as, for example, Pfaltz and Bauer, Inc. and K&K Laboratories, Division of ICN Biochemicals, Inc. Further salts of nicotine are described in U.S. Patent Nos. 9,738,622; 9,896,429; 10,464,917; 10,508,096; 10,556,880; 10,865,192; and 11,136,305, all to R.J. Reynolds, all of which are incorporated herein by reference in their entireties. It is noted that while the second nicotine component is described herein as optionally being in the form of a nicotine salt, this nomenclature is also intended to encompass nicotine cocrystals and salt-cocrystal complexes, which may vary in the interaction between nicotine and its coformer, such as those described in the patents of R.J. Reynolds referenced herein above. Thus, "nicotine salts", as used herein, unless the context dictates otherwise, encompasses forms of nicotine and at least one other coformer in which both the nicotine and the coformer are in ionic form (nicotine salts); forms of nicotine and at least one other coformer in which both the nicotine and the coformer are in neutral form (nicotine cocrystals); as well as hybrid combination structures having features of both salts and cocrystals (nicotine salt-cocrystals).

[0131] The second nicotine component, in some embodiments, is selected from the group consisting of nicotine free base, nicotine salts, such as hydrochloride, dihydrochloride, monotartrate, bitartrate, sulfate, salicylate, and zinc nicotine chloride. In certain embodiments, the second nicotine component is a nicotine extract purified from tobacco. In certain embodiments, the second nicotine component is pharmaceutical grade (e.g., USP) nicotine. In some embodiments, the second nicotine component can be incorporated into the composition / product in the form of an aqueous solution, the concentration of nicotine contained therein can vary. In some embodiments, a solution having a nicotine concentration of about 7% to about 25% by weight can be used. Calculation of the required amount of solution to be added must take into account the concentration and desired content of the second nicotine component in the final composition / product.

[0132] If a second nicotine component is included, the amount may vary and may depend in part on the exact form of the second nicotine component (e.g., nicotine free base or nicotine salt). In some embodiments, if a second nicotine component is included, the amount of nicotine provided by the second nicotine component may vary from 0%, about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, or about 60% to about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 98%, based on the total weight of all nicotine components in a given composition. Certain non-limiting exemplary amounts of the second nicotine component incorporated within a given composition can range, for example, from about 0.01% to about 10% by weight, e.g., from about 0.1 to about 1.5% by weight, from about 0.5% to about 5% by weight, from about 1% to about 5% by weight, or from about 0.5% to about 3% by weight, based on the total weight of the mixture to be included within the pouch product.

[0133] The ratio of the first nicotine component to the second nicotine component (if present) in the compositions and products provided herein may vary. In some embodiments, the compositions and products contain nicotine entirely or mainly in the form of the first nicotine component. In some embodiments, the compositions and products contain nicotine mainly in the form of the second nicotine component. In some embodiments, the first and second nicotine components are provided in approximately equal amounts by weight. Certain examples include, but are not limited to, compositions in which 100% of the nicotine is in the form of a nicotine polymer complex, compositions in which 50% of the nicotine is in the form of a nicotine polymer complex and 50% of the nicotine is in the form of a nicotine free base or salt; and compositions in which 80% of the nicotine is in the form of a nicotine polymer complex and 20% of the nicotine is in the form of a nicotine free base or salt, and all ranges therebetween.

[0134] The total amount of nicotine provided by the nicotine component(s) provided herein may also vary. In some embodiments, pouches are provided that include compositions containing about 5 mg to about 25 mg of nicotine, such as about 5 mg to about 20 mg of nicotine, and about 10 mg to about 15 mg of nicotine. Certain non-limiting examples of pouch compositions include about 5 mg of nicotine per pouch, about 10 mg of nicotine per pouch, about 15 mg of nicotine per pouch, or about 20 mg of nicotine per pouch. Certain embodiments, for example, when contained within a pouch product, include about 2 to about 4% of the nicotine polymer complex and about 1 to about 3% of the second nicotine component; about 3 to about 5% of the nicotine polymer complex and about 1 to about 3% of the second nicotine component; and about 8 to about 10% of the nicotine polymer complex and about 1 to about 3% of the second nicotine component, all on a weight basis based on the total composition.

[0135] In some embodiments, at least a portion of one or more of the nicotine components in the compositions and products provided herein is bound to one or more organic acids through ion pairing. In some embodiments, at least a portion of the basic amine is bound to at least a portion of the organic acid or its alkali metal salt. Depending on a number of variables (concentration, pH, nature of the organic acid, etc.), the nicotine component(s) present in the composition can exist in a number of forms, including as an ion pair in solution (i.e., fully solvated), as a free base, as a cation, as a salt, or any combination thereof. In some embodiments, the bond between nicotine and at least a portion of the organic acid or its alkali metal salt or alkaline earth metal salt is in the form of an ion pair between the basic amine and the conjugate base of the organic acid.

[0136] Ion pairing describes the partial binding of oppositely charged ions in a relatively concentrated solution to form distinct chemical species called ion pairs. The strength of the binding (i.e., ion pairing) depends on the electrostatic force of attraction between the positive and negative ions (i.e., the protonated basic amine and the conjugate base of the organic acid). By "conjugate base" is meant the base generated from the deprotonation of the corresponding acid (e.g., benzoate ion is the conjugate base of benzoic acid). On average, a certain population of these ion pairs will be present at any one time, but the formation and dissociation of ion pairs is continuous. In the compositions disclosed herein and / or during use of the compositions in the oral cavity (e.g., upon contact with saliva), nicotine and the conjugate base of the organic acid are at least partially present in the form of ion pairs. Without wishing to be bound by theory, it is believed that such ion pairing can minimize the chemical degradation of nicotine and / or enhance the availability of basic amines (e.g., nicotine) in the oral cavity. Without wishing to be bound by theory, it is believed that such ion pairing can also enhance the release of nicotine from the oral compositions disclosed herein when nicotine is present in a resin-bound form.

[0137] Those skilled in the art will recognize that the extent of ion pairing in the disclosed compositions may vary both before and during use by the consumer based on, for example, pH, the nature of the organic acid, the concentration of the basic amine (e.g., nicotine), the concentration of the organic acid or conjugate base of the organic acid present in the composition, the moisture content of the composition, the ionic strength of the composition, and the like. Those skilled in the art will also recognize that ion pairing is an equilibrium process that is influenced by the aforementioned variables. Thus, the extent of ion pairing is difficult or impossible to quantify by calculation or direct observation. However, the presence of ion pairing can be demonstrated via surrogate measurements, for example, partitioning between octanol and water, or membrane permeation of, for example, an aqueous solution of nicotine plus organic acid and / or their conjugate base. In particular, octanol-water partitioning, which favors the distribution of basic amine-organic acid ion pairs into octanol, predicts good absorption of basic amines present in the composition through the oral mucosa.

[0138] organic acid As described hereinabove, in some embodiments, the composition comprises an organic acid. As used herein, the term "organic acid" refers to an organic (i.e., carbon-based) compound characterized by acid properties. Typically, organic acids are relatively weak acids (i.e., they do not completely dissociate in the presence of water), such as carboxylic acids (-CO2H) or sulfonic acids (-SO2OH). As used herein, reference to an organic acid refers to an organic acid that is intentionally added. In this context, an organic acid can be intentionally added as a particular composition component, as opposed to an organic acid that is simply naturally present as a constituent of another composition component (e.g., a small amount of organic acid that may be naturally present in a composition component, e.g., tobacco material).

[0139] Suitable organic acids usually have a range of lipophilicity (i.e., have polarity that confers an appropriate balance between aqueous and organic solubility). Lipophilicity is conveniently measured in terms of logP, the partition coefficient of a molecule between a lipophilic phase and an aqueous phase (usually water). Usually, the lipophilic phase is octanol, but other lipophilic solvents can also be used. For the avoidance of doubt, logP referred to in this disclosure means the partition coefficient between octanol and water. Similarly, references to logD values ​​herein mean that the logD is obtained by partitioning between octanol and water (buffered to a particular pH value). A logP (or logD) that favors distribution of the nicotine-organic acid ion pair into the lipophilic phase (positive logP or logD) predicts good absorption of the nicotine present in the composition through the oral mucosa.

[0140] Typically, the lipophilicity of suitable organic acids, as measured by logP, ranges from about 1 to about 12 (more soluble in octanol than in water). In some embodiments, the organic acid has a logP value of about 1 to about 12, e.g., from about 1.0, about 1.5, about 2.0, about 2.5, about 3.0, about 3.5, about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, about 7.0, about 7.5, or about 8.0, to about 8.5, about 9.0, about 9.5, about 10.0, about 10.5, about 11.0, about 11.5, or about 12.0.

[0141] Without wishing to be bound by theory, it is believed that moderately lipophilic organic acids (e.g., logP of about 1.4 to about 4.5) form ion pairs with nicotine, which is bipolar, resulting in favorable octanol-water partitioning of the ion pair, thus partitioning nicotine into octanol versus water. As discussed above, such partitioning into octanol predicts favorable oral availability.

[0142] In certain embodiments, the organic acid has a log P value of about 3.0 to about 8.0, about 10.0, or even 12.0. In some embodiments, the presence of certain solvents or solubilizers (e.g., inclusion of glycerin or propylene glycol in the composition) may be beneficial for very lipophilic organic acids (e.g., greater than about 4.5) to solubilize the organic acid and its corresponding salt or ion pair with a basic amine.

[0143] In some embodiments, the organic acid is a carboxylic acid or a sulfonic acid. The carboxylic acid or sulfonic acid functional group may, for example, be an organic acid having 1 to 20 carbon atoms (C1 to C 20 ) may be attached to any alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group having the formula: In some embodiments, the organic acid is an alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl carboxyl or sulfonic acid.

[0144] As used herein, "alkyl" refers to any straight or branched chain hydrocarbon. The alkyl group may be saturated (i.e., all sp 3 As used herein, the term "unsaturated" refers to a carbon-carbon, sp , or cyclic alkyl group at one or more positions within an alkyl group. 2It refers to the presence of a double bond. Unsaturated alkyl groups may be monounsaturated or polyunsaturated. Representative straight chain alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, and n-hexyl. Branched chain alkyl groups include, but are not limited to, isopropyl, sec-butyl, isobutyl, tert-butyl, isopentyl, and 2-methylbutyl. Representative unsaturated alkyl groups include, but are not limited to, ethylene or vinyl, allyl, 1-butenyl, 2-butenyl, isobutylenyl, 1-pentenyl, 2-pentenyl, 3-methyl-1-butenyl, 2-methyl-2-butenyl, 2,3-dimethyl-2-butenyl, and the like. The alkyl groups may be unsubstituted or substituted.

[0145] "Cycloalkyl" as used herein refers to a carbocyclic group, which may be monocyclic or bicyclic. Cycloalkyl groups include rings having 3 to 7 carbon atoms as a monocycle or rings having 7 to 12 carbon atoms as a bicycle. Examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Cycloalkyl groups may be unsubstituted or substituted and may contain one or more sites of unsaturation (e.g., cyclopentenyl or cyclohexenyl).

[0146] The term "aryl" as used herein refers to a carbocyclic aromatic group. Examples of aryl groups include, but are not limited to, phenyl and naphthyl. Aryl groups can be unsubstituted or substituted.

[0147] "Heteroaryl" and "heterocycloalkyl," as used herein, refer to an aromatic or non-aromatic ring system, respectively, in which one or more ring atoms are heteroatoms, such as nitrogen, oxygen, and sulfur. A heteroaryl or heterocycloalkyl group contains up to 20 carbon atoms and 1-3 heteroatoms selected from N, O, and S. A heteroaryl or heterocycloalkyl may be monocyclic having 3-7 ring members (e.g., 2-6 carbon atoms and 1-3 heteroatoms selected from N, O, and S) or bicyclic having 7-10 ring members (e.g., 4-9 carbon atoms and 1-3 heteroatoms selected from N, O, and S), such as a bicyclo[4,5], [5,5], [5,6], or [6,6] system. Examples of heteroaryl groups include, by way of example and not limitation, pyridyl, thiazolyl, tetrahydrothiophenyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, thianaphthalenyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, isoxazolyl, pyrazinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, 1H-indazolyl, purinyl, 4H- Examples include quinolidinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 4aH-carbazolyl, carbazolyl, phenanthridinyl, acridinyl, pyrimidinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, furazanyl, phenoxazinyl, isochromanyl, chromanyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, benzotriazolyl, benzisoxazolyl, and isatinoyl.Examples of heterocycloalkyl include, by way of example and not limitation, dihydropyridyl, tetrahydropyridyl (piperidyl), tetrahydrothiophenyl, piperidinyl, 4-piperidonyl, pyrrolidinyl, 2-pyrrolidonyl, tetrahydrofuranyl, tetrahydropyranyl, bis-tetrahydropyranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, octahydroisoquinolinyl, piperazinyl, quinuclidinyl, and morpholinyl. Heteroaryl and heterocycloalkyl groups can be unsubstituted or substituted.

[0148] "Substituted" as used herein and when applied to any of the above alkyl, aryl, cycloalkyl, heteroaryl, and heterocyclyl means that one or more hydrogen atoms are each independently replaced with a substituent. Exemplary substituents include, but are not limited to, -Cl, Br, F, alkyl, -OH, -OCH3, NH2, -NHCH3, -N(CH3)2, -CN, -NC(=O)CH3, -C(=O)-, -C(=O)NH2, and -C(=O)N(CH3)2. Whenever a group is described as "optionally substituted," the group can be substituted with one or more of the above substituents, selected independently for each occurrence. In some embodiments, the substituents can be one or more methyl groups or one or more hydroxyl groups.

[0149] In some embodiments, the organic acid is an alkyl carboxylic acid. Non-limiting examples of alkyl carboxylic acids include formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, and the like. In some embodiments, the organic acid is an alkyl sulfonic acid. Non-limiting examples of alkyl sulfonic acids include propane sulfonic acid, heptane sulfonic acid, and octane sulfonic acid. In some embodiments, the alkyl carboxyl or sulfonic acid is substituted with one or more hydroxyl groups. Non-limiting examples include glycolic acid, 4-hydroxybutyric acid, and lactic acid. In some embodiments, the organic acid can include more than one carboxylic acid group or more than one sulfonic acid group (e.g., 2, 3 or more carboxylic acid groups). Non-limiting examples include oxalic acid, fumaric acid, maleic acid, and glutaric acid. In organic acids containing multiple carboxylic acids (e.g., 2 to 4 carboxylic acid groups), one or more of the carboxylic acid groups may be esterified. Non-limiting examples include monoethyl succinate, monomethyl fumarate, monomethyl citrate, or dimethyl citrate.

[0150] In some embodiments, the organic acid can contain more than one carboxylic acid group and one or more hydroxyl groups. Non-limiting examples of such acids include tartaric acid, citric acid, and the like. In some embodiments, the organic acid is an aryl carboxylic acid or an aryl sulfonic acid. Non-limiting examples of aryl carboxylic and sulfonic acids include benzoic acid, toluic acid, salicylic acid, benzenesulfonic acid, and p-toluenesulfonic acid.

[0151] Further non-limiting examples of organic acids that may be useful in certain embodiments include 2,2-dichloroacetic acid, 2-hydroxyethanesulfonic acid, 2-oxoglutaric acid, 4-acetamidobenzoic acid, 4-aminosalicylic acid, adipic acid, ascorbic acid (L), aspartic acid (L), alpha-methylbutyric acid, camphoric acid (+), camphor-10-sulfonic acid (+), cinnamic acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, furoic acid, and galactaric acid. , gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, isovaleric acid, lactobionic acid, lauric acid, levulinic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, oleic acid, palmitic acid, pamoic acid, phenylacetic acid, pyroglutamic acid, pyruvic acid, sebacic acid, stearic acid, and undecylenic acid.

[0152] Examples of suitable acids include, but are not limited to, the list of organic acids in Table 1.

[0153] [Table 1]

[0154] In some embodiments, the organic acid is a monoester of a diacid or polyacid, such as monooctyl succinate, monooctyl fumarate, etc. For example, in some embodiments, the organic acid is a monoester of a dicarboxylic acid or polycarboxylic acid. In some embodiments, the dicarboxylic acid is malonic acid, succinic acid, glutaric acid, adipic acid, fumaric acid, maleic acid, or a combination thereof. In some embodiments, the dicarboxylic acid is succinic acid, glutaric acid, fumaric acid, maleic acid, or a combination thereof. In some embodiments, the dicarboxylic acid is succinic acid, glutaric acid, or a combination thereof.

[0155] In some embodiments, the alcohol forming monoester of a dicarboxylic acid is a lipophilic alcohol. Examples of suitable lipophilic alcohols include, but are not limited to, octanol, menthol, and tocopherol. In some embodiments, the organic acid is an octyl monoester of a dicarboxylic acid, such as monooctyl succinate, monooctyl fumarate, and the like. In some embodiments, the organic acid is a monomenthyl ester of a dicarboxylic acid. Certain menthyl esters may be desirable in the oral compositions described herein because they can provide a cooling sensation upon use of a product containing the composition. In some embodiments, the organic acid is monomenthyl succinate, monomenthyl fumarate, monomenthyl glutarate, or combinations thereof. In some embodiments, the organic acid is a monotocopheryl ester of a dicarboxylic acid. Certain tocopheryl esters may be desirable in the oral compositions described herein because they can provide an antioxidant effect. In some embodiments, the organic acid is tocopheryl succinate, tocopheryl fumarate, tocopheryl glutarate, or combinations thereof.

[0156] In some embodiments, the organic acid is a carotenoid derivative having one or more carboxylic acids. Carotenoids are tetraterpenes, meaning that they are generated from eight isoprene molecules and contain 40 carbon atoms. Thus, they are usually lipophilic due to the presence of long unsaturated aliphatic chains, and are generally yellow, orange, or red in color. Certain carotenoid derivatives can be advantageous in oral compositions by providing both ion pairing and acting as coloring agents in the composition. In some embodiments, the organic acid is 2E,4E,6E,8E,10E,12E,14E,16Z,18E)-20-methoxy-4,8,13,17-tetramethyl-20-oxoicosa-2,4,6,8,10,12,14,16,18-nonaenoic acid (bixin) or an isomer thereof. Bixin is an apocarotenoid found in annatto seeds from the achiote tree (Bixa orellana) and is the naturally occurring pigment that provides annatto with its reddish-orange color. Bixin is soluble in fats and alcohol but insoluble in water, and when isolated, is chemically unstable and is converted via isomerization to the double bond isomer, trans-bixin (β-bixin), which has the following structure:

[0157] [ka]

[0158] In some embodiments, the organic acid is (2E,4E,6E,8E,10E,12E,14E,16E,18E)-4,8,13,17-tetramethylicosa-2,4,6,8,10,12,14,16,18-nonenedioic acid (norbixin), a water soluble hydrolysis product of bixin, having the following structure:

[0159] [ka]

[0160] The selection of an organic acid may further depend on additional properties, in addition to or without consideration of the logP value. For example, the organic acid should be one that is recognized as safe for human consumption and has acceptable flavor, odor, volatility, stability, etc. The determination of suitable organic acids is within the purview of one of ordinary skill in the art.

[0161] In some embodiments, the organic acid is benzoic acid, toluic acid, benzenesulfonic acid, toluenesulfonic acid, hexanoic acid, heptanoic acid, decanoic acid, or octanoic acid. In some embodiments, the organic acid is benzoic acid, octanoic acid, or decanoic acid. In some embodiments, the organic acid is octanoic acid. In some embodiments, the organic acid is benzoic acid.

[0162] In some embodiments, more than one organic acid may be present. For example, a composition may include two, or three, or four or more organic acids. Thus, reference herein to an "organic acid" contemplates a mixture of two or more organic acids. The relative amounts of the organic acids may vary. For example, a composition may include equal amounts of two, or three or more organic acids, or may include different relative amounts. Thus, it is possible to include certain organic acids (e.g., citric acid or myristic acid) that have logP values ​​outside of the desired range, such that when combined with other organic acids, they provide a desired average logP range for the combination. In some embodiments, it may be desirable to include organic acids that provide desirable organoleptic properties, stability, for example, but not limited to, as flavor ingredients in compositions that have logP values ​​outside of the desired range for a purpose. Additionally, certain lipophilic organic acids have adverse flavor and / or aroma characteristics that preclude their presence as the only organic acid (e.g., in equimolar or greater amounts compared to nicotine). Without wishing to be bound by theory, it is believed that combinations of different organic acids can provide desirable ion pairing while keeping the concentration of any single organic acid in the composition below a threshold that has been found to be undesirable from a sensory standpoint. For example, in some embodiments, the organic acid can include, for example, about 1 to about 5 or more molar equivalents of benzoic acid in combination with about 0.2 molar equivalents of octanoic acid or a salt thereof, and 0.2 molar equivalents of decanoic acid or a salt thereof relative to the basic amine-containing active ingredient (e.g., nicotine).

[0163] In some embodiments, the organic acid is a combination of any two organic acids selected from the group consisting of benzoic acid, toluic acid, benzenesulfonic acid, toluenesulfonic acid, hexanoic acid, heptanoic acid, decanoic acid, and octanoic acid. In some embodiments, the organic acid is a combination of benzoic acid, octanoic acid, and decanoic acid, or benzoic acid and octanoic acid. In some embodiments, the composition comprises citric acid in addition to one or more of benzoic acid, toluic acid, benzenesulfonic acid, toluenesulfonic acid, hexanoic acid, heptanoic acid, decanoic acid, and octanoic acid.

[0164] In some embodiments, the composition comprises an alkali metal salt of an organic acid or an alkaline earth metal salt of an organic acid. For example, at least a portion of the organic acid may be present in the composition in the form of an alkali metal salt or an alkaline earth metal salt. Suitable alkali metals include lithium, sodium, and potassium. In some embodiments, the alkali metal is sodium or potassium. In some embodiments, the alkali metal is sodium. In some embodiments, the composition comprises an organic acid and a sodium salt of an organic acid.

[0165] In some embodiments, the composition comprises an alkali metal salt of an organic acid or an alkaline earth metal salt of an organic acid. For example, at least a portion of the organic acid may be present in the composition in the form of an alkali metal salt or an alkaline earth metal salt. Suitable alkali metals include lithium, sodium, and potassium. In some embodiments, the alkali metal is sodium or potassium. In some embodiments, the alkali metal is sodium. In some embodiments, the composition comprises an organic acid and a sodium salt of an organic acid. Suitable alkaline earth metals include, but are not limited to, magnesium and calcium. In some embodiments, the composition comprises an organic acid and a calcium salt of an organic acid. Without wishing to be bound by theory, it is believed that multivalent cations, such as calcium or magnesium ions provided by a calcium or magnesium salt of an organic acid, respectively, or alternatively or in addition, calcium or magnesium ions provided by an inorganic calcium or magnesium salt, respectively, as further described herein below, can increase the ionic strength of the composition. Again, without wishing to be bound by any particular theory, it is believed that the increase in ionic strength of the composition provided by, for example, the presence of a salt, e.g., a calcium salt of an organic acid, can enhance one or more of the following: the extent of ion pairing of a basic amine-containing active ingredient, such as nicotine, with the conjugate base of the organic acid; a desirable composition pH (e.g., around 6); and enhanced nicotine release when nicotine is present in a resin-bound form (e.g., nicotine polacrilex). Surprisingly, in accordance with the present disclosure, it has been found that the release of nicotine from nicotine polacrilex is enhanced by the presence of certain calcium salts. Specifically, referring to Examples 13 and 16 and Figures 4 and 5, compositions comprising nicotine polacrilex and certain calcium salts achieved greater release of nicotine from nicotine polacrilex than was achieved in the absence of such salts.

[0166] Suitable calcium salts of organic acids include, but are not limited to, calcium gluconate, calcium glycerol phosphate, calcium lactate, calcium lactate gluconate, and combinations thereof. Without wishing to be bound by theory, it is believed that in some embodiments, the presence of one or more calcium salts of organic acids may be preferred due to the lower perception of "salty" in oral products containing such salts, compared to inorganic calcium salts (e.g., calcium chloride or magnesium chloride) or alkali metal salts (e.g., sodium chloride or potassium chloride).

[0167] Certain such calcium salts (including, for example, but not limited to, calcium glycerol phosphate and calcium lactate gluconate) are particularly advantageous, for example, because they are food grade additives with a neutral taste. In some embodiments, the inclusion of such calcium salts advantageously provides enhanced properties, such as enhanced nicotine release, as well as log D, much lower pH, etc., as shown, for example, in Example 5 / Figure 4.

[0168] In some embodiments, the composition comprises benzoic acid and sodium benzoate, octanoic acid and sodium octanoate, decanoic acid and sodium decanoate, or combinations thereof. In some embodiments, the composition comprises benzoic acid and sodium benzoate. In some embodiments, the composition comprises sodium benzoate. In some embodiments, the composition comprises calcium benzoate. In some embodiments, the composition comprises a mixture of sodium benzoate and calcium benzoate. In some embodiments, the composition comprises calcium gluconate, calcium glycerol phosphate, calcium lactate, calcium lactate gluconate, or combinations thereof, alone or in combination with a sodium salt of an organic acid, e.g., sodium benzoate.

[0169] In some embodiments, the ratio of organic acid to salt of organic acid (e.g., sodium and / or calcium salt) is from about 0.1 to about 10, e.g., from about 0.1, about 0.25, about 0.3, about 0.5, about 0.75, or about 1, to about 2, about 5, or about 10. For example, in some embodiments, both the organic acid and its salt are added to the other components of the composition, and the organic acid is added in an amount in excess of the salt, in an equimolar amount to the salt, or as a portion of the salt (e.g., sodium salt). Those skilled in the art will recognize that the relative amounts are determined by the desired pH of the composition, as well as the desired ionic strength. For example, the organic acid may be added in an amount that results in the desired pH level of the composition, while the alkali metal (e.g., sodium) salt is added in an amount that results in the desired range of ion pairing. Those skilled in the art will understand that the amount of organic acid (i.e., the protonated form) present in a composition relative to the alkali metal salt or conjugate base form present in the composition will vary depending on the pH of the composition and the pKa of the organic acid, as well as the actual relative amounts initially added to the composition.

[0170] The amount of organic acid or its salt relative to the basic amine-containing active ingredient (e.g., nicotine) present in the composition can vary. Generally, as the concentration of the organic acid (or its conjugate base) increases, the percentage of the basic amine-containing active ingredient (e.g., nicotine) that forms an ion pair with the organic acid increases. This is usually measured by the logP (log of the partition coefficient). 10 ), increases the partitioning of the basic amine-containing active ingredient (e.g., nicotine) in the form of an ion pair into octanol versus water. In some embodiments, the composition comprises from about 0.05, about 0.1, about 1, about 1.5, about 2, or about 5, to about 10, about 15, or about 20 molar equivalents of an organic acid, salt thereof, or combination thereof relative to the basic amine-containing active ingredient (e.g., nicotine), calculated as the free base amine-containing active ingredient.

[0171] In some embodiments, the composition comprises about 1 to about 10, or about 2 to about 5 molar equivalents of an organic acid, salt thereof, or combination thereof, relative to nicotine, on a free base nicotine basis. In some embodiments, the organic acid, salt thereof, or combination thereof is present in a molar ratio with the basic amine-containing active ingredient (e.g., nicotine) of about 1, about 2, about 3, about 4, or about 5, to about 6, about 7, about 8, about 9, or about 10. In embodiments where more than one organic acid, salt thereof, or both are present, such molar ratios are understood to reflect the totality of organic acids present.

[0172] In certain embodiments, the inclusion of the organic acid is sufficient to provide a pH of the composition of about 3.0 to about 9.5, e.g., about 3.0 to about 9.0, or about 3.0 to about 8.5, or about 3.0 to about 8.0, or about 3.5 to about 7.5, or about 4.5 to about 7.0, or about 5.5 to about 7.0, or about 4.0 to about 5.5, or about 6.0 to about 9.0, or about 7.0 to about 9.5. In some embodiments, the inclusion of the organic acid is sufficient to provide a pH of the composition of about 3.0, about 3.5, about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, about 7.0, about 7.5, about 8.0, about 8.5, or about 9.0. In some embodiments, the inclusion of an organic acid is sufficient to provide a pH of the composition of about 4.5 to about 6.5, e.g., about 4.5, about 5.0, or about 5.5, to about 6.0, or about 6.5. In some embodiments, the organic acid is provided in an amount sufficient to provide a pH of the composition of about 5.5 to about 6.5, e.g., about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, or about 6.0, to about 6.1, about 6.2, about 6.3, about 6.4, or about 6.5. In other embodiments, a mineral acid (e.g., hydrochloric acid, sulfuric acid, phosphoric acid, etc.) is added to adjust the pH of the composition to a desired value. In particular, at alkaline pH values ​​(e.g., about 7.5 to about 9), nicotine exists primarily in the free base form (and thus exhibits high partitioning into octanol), while at acidic pH values ​​(e.g., about 6.5 to about 4), nicotine exists primarily in the protonated form (and thus exhibits lower partitioning into octanol). In some embodiments, a buffering agent, such as a carbonate or bicarbonate, is added to adjust and / or maintain the desired pH value. Other suitable buffering agents are described further herein below.

[0173] In some embodiments, the organic acid is added to the other composition components as a free acid, in pure form (i.e., natural solid or liquid form) or as a solution, e.g., a solution in water. In some embodiments, the salt of the organic acid is added to the other composition components in pure form or as a solution, e.g., a solution in water. In some embodiments, the organic acid and the basic amine-containing active ingredient (e.g., nicotine) are combined to form a salt, either the salt is formed prior to addition to the composition, or the salt is formed therein and present in the composition as such. In other embodiments, the organic acid and the basic amine-containing active ingredient (e.g., nicotine) are present in the composition as individual components and form an ion pair upon contact with moisture (e.g., saliva in the consumer's mouth).

[0174] In some embodiments, the composition further comprises a solubility enhancer that increases the solubility of one or more of the organic acids or salts thereof. Suitable solubility enhancers include, but are not limited to, humectants as described herein, such as glycerin or propylene glycol.

[0175] Filler Ingredients The material in the pouch described herein typically includes at least one particulate filler component. Such particulate filler components can fulfill multiple functions, such as enhancing certain sensory properties, such as enhancing texture and mouthfeel, enhancing the cohesiveness or compressibility of the product, and the like. Generally, the filler components are particulate materials and are cellulose-based. For example, suitable particulate filler components are any non-tobacco plant material or derivatives thereof, including cellulose materials from such sources. Examples of cellulosic non-tobacco plant materials include grains (e.g., corn, oats, barley, rye, buckwheat, etc.), sugar beet (e.g., FIBREX® brand filler available from International Fiber Corporation), bran fiber, and mixtures thereof. Non-limiting examples of derivatives of non-tobacco plant materials include starches (e.g., from potato, wheat, rice, corn), natural cellulose, and modified cellulosic materials. Additional examples of potential particulate filler components include maltodextrin, dextrose, calcium carbonate, calcium phosphate, lactose, mannitol, xylitol, and sorbitol. Combinations of fillers may also be used.

[0176] "Starch" as used herein can refer to pure starch, modified starch, or starch derivatives from any source. Starch is usually present in granular form in almost all green plants and in various types of plant tissues and organs (e.g., seeds, leaves, rhizomes, roots, tubers, shoots, fruits, grains, and stems). Starch may vary in composition and granule shape and size. Starches from different sources often have different chemical and physical characteristics. A particular starch can be selected for inclusion in a mixture based on the ability of the starch material to impart a particular organoleptic property to the composition. Starch from various sources can be used. For example, major sources of starch include cereals (e.g., rice, wheat, and corn) and root vegetables (e.g., potato and cassava). Other examples of starch sources include acorn, arrowroot, arracachá, banana, barley, legumes (e.g., broad bean, lentil, mung bean, pea, chickpea), breadfruit, buckwheat, canna, chestnut, colocasia, dogtooth violet, kudzu, malanga, millet, oat, oka, Polynesian arrowroot, sago, sorghum, sweet potato, quinoa, rye, tapioca, taro, tobacco, water chestnut, and yam. Certain starches are modified starches. Modified starches have undergone one or more structural changes, often designed to alter their high thermal properties. Some starches have been developed by genetic engineering and are considered "genetically modified" starches. Other starches are obtained and subsequently modified physically (e.g., by heating, cold water swelling, etc.), chemically, or enzymatically. For example, modified starch may be starch that has been subjected to chemical reactions such as esterification, etherification, oxidation, depolymerization (thinning) by acid catalysis or oxidation in the presence of a base, bleaching, transglycosylation and depolymerization (e.g., dextrinization in the presence of a catalyst), crosslinking, acetylation, hydroxypropylation and / or partial hydrolysis. Enzymatic treatments include exposing native starch to enzyme isolates or concentrates, microbial enzymes and / or enzymes derived from plant material, e.g., exposing corn starch to amylases present in corn kernels to modify corn starch.Other starches are modified by heat treatment, e.g., pregelatinization, dextrinization and / or cold water swelling processes. Certain modified starches include phosphated starch, glycerol crosslinked starch, phosphated crosslinked starch esterified with sodium trimetaphosphate, phosphated phosphated crosslinked starch, acetylated phosphated crosslinked starch, starch acetate esterified with acetic anhydride, starch acetate esterified with vinyl acetate, acetylated adipate crosslinked starch, acetylated glycerol crosslinked starch, hydroxypropylated starch, hydroxypropylated glycerol crosslinked starch, and sodium starch octenylsuccinate.

[0177] In some embodiments, the particulate filler component is a cellulose material or a cellulose derivative. One particulate filler component particularly suitable for use in the products described herein is microcrystalline cellulose ("MCC"). MCC can be synthetic, semi-synthetic, or derived entirely from natural cellulose. MCC can be selected from the group consisting of AVICEL® grades PH-100, PH-102, PH-103, PH-105, PH-112, PH-113, PH-200, PH-300, PH-302, VIVACEL® grades 101, 102, 12, 20, and EMOCEL® grades 50M and 90M, and the like, and mixtures thereof. In one embodiment, the mixture includes MCC as a particulate filler component. The amount of MCC present in the mixtures described herein can vary depending on the desired properties.

[0178] The amount of particulate filler component can vary, but is typically up to about 75 weight percent of the material contained in the pouch (i.e., the mixture) based on the total weight of the mixture. A typical range of particulate filler material (e.g., MCC) in the mixture can be from about 10 to about 75 weight percent, e.g., from about 10, about 15, about 20, about 25, or about 30, to about 35, about 40, about 45, or about 50 weight percent (e.g., about 20 to about 50 weight percent, about 25 to about 45 weight percent, or about 50 to about 80 weight percent, or about 60 to about 80 weight percent) of the total weight of the mixture. In certain embodiments, the amount of particulate filler material is at least about 10 weight percent, e.g., at least about 20 weight percent, or at least about 25 weight percent, or at least about 30 weight percent, or at least about 35 weight percent, or at least about 40 weight percent based on the total weight of the mixture.

[0179] In one embodiment, the particulate filler component further comprises a cellulose derivative or a combination of such derivatives. In some embodiments, the mixture comprises about 1 to about 10 wt. % of the cellulose derivative, and certain embodiments comprise about 1 to about 5 wt. % of the cellulose derivative, based on the total weight of the mixture. In certain embodiments, the cellulose derivative is a cellulose ether (including carboxyalkyl ether), which refers to a cellulose polymer in which the hydrogen of one or more hydroxyl groups in the cellulose structure is replaced with an alkyl, hydroxyalkyl, or aryl group. Non-limiting examples of such cellulose derivatives include methylcellulose, hydroxypropylcellulose ("HPC"), hydroxypropylmethylcellulose ("HPMC"), hydroxyethylcellulose, and carboxymethylcellulose ("CMC"). In one embodiment, the cellulose derivative is one or more of methylcellulose, HPC, HPMC, hydroxyethylcellulose, and CMC. In one embodiment, the cellulose derivative is HPC. In some embodiments, the mixture comprises about 0 wt. % to about 5 wt. % of HPC, for example, about 1 wt. % to about 3 wt. % of HPC, based on the total weight of the mixture.

[0180] In some further embodiments, the composition includes as a filler a by-product of the pulping process, such as citrus rind. In some embodiments, the composition includes as a filler wheat straw. Such fillers can be used in combination with any of the types of particulate fillers referenced herein above.

[0181] water The water content of the mixture within the pouch products described herein prior to use of the product by the consumer can vary depending on the desired properties. Typically, the mixture present within the product prior to insertion into the user's mouth contains less than about 60 weight percent water, typically about 1 to about 60 weight percent water, such as about 5 to about 55 weight percent water, about 10 to about 50 weight percent water, about 20 to about 45 weight percent water, or about 25 to about 40 weight percent water, including amounts of water of at least about 5 weight percent, at least about 10 weight percent water, at least about 15 weight percent water, and at least about 20 weight percent water.

[0182] In some embodiments, the mixture comprises a lower moisture content than some conventional mixtures for inclusion in a pouch product. For example, in some embodiments, the mixture comprises water in an amount of up to about 25% by weight or up to about 20% by weight, based on the total weight of the mixture. In some embodiments, the moisture content of the granular composition is from 1% to about 12% by weight, e.g., less than about 8% by weight, less than about 7% by weight, less than about 6% by weight, less than about 5% by weight, or less than about 4% by weight, based on the total weight of the granular composition. Exemplary embodiments may comprise water in an amount of from about 15% to about 25%, e.g., from about 17% to about 20%.

[0183] Flavoring Agent As used herein, a "flavoring agent" or "flavoring agent" is any flavorful or fragrant substance capable of modifying the sensory characteristics associated with an oral product. Examples of sensory characteristics that can be modified with a flavoring agent include taste, mouthfeel, moistness, cooling / heating, and / or flavor / aroma. Flavoring agents can be natural or synthetic, and the resulting flavor characteristics can be described as fresh, sweet, herbal, confectionery, floral, fruity, or spicy, without limitation. Specific types of flavors include, but are not limited to, vanilla, coffee, chocolate / cocoa, cream, mint, spearmint, menthol, peppermint, wintergreen, eucalyptus, lavender, cardamom, nutmeg, cinnamon, clove, cascarilla, sandalwood, honey, jasmine, ginger, anise, sage, licorice, lemon, orange, apple, peach, lime, cherry, strawberry, trigeminal sensate, melatonin, terpenes, and any combination thereof. See also Leffingwell et al., Tobacco Flavoring for Smoking Products, RJ Reynolds Tobacco Company (1972), which is incorporated herein by reference. Flavoring agents can also include components that are considered to be humectants, coolants, or smoothing agents, such as eucalyptus. These flavoring agents may be provided pure (i.e., alone) or in complexes, and may be utilized as concentrates or flavoring packages (e.g., spearmint and menthol, orange and cinnamon; lime, pineapple, etc.). Representative types of components are also described in U.S. Patent No. 5,387,416 to White et al.; U.S. Patent Application Publication No. 2005 / 0244521 to Strickland et al.; and PCT Application No. WO 05 / 041699 to Quinter et al., each of which is incorporated herein by reference. In some cases, flavoring agents may be provided in spray-dried or liquid form.

[0184] Flavoring agents generally include at least one volatile flavor ingredient. As used herein, "volatile" refers to a chemical that readily forms vapor at ambient temperature (i.e., a chemical that has a high vapor pressure at a given temperature compared to non-volatile substances). Typically, volatile flavor ingredients have a molecular weight of less than about 400 Da and often contain at least one carbon-carbon double bond, carbon-oxygen double bond, or both. In one embodiment, the at least one volatile flavor ingredient includes one or more alcohols, aldehydes, aromatic hydrocarbons, ketones, esters, terpenes, terpenoids, or combinations thereof. Non-limiting examples of aldehydes include vanillin, ethyl vanillin, p-anisaldehyde, hexanal, furfural, isovaleraldehyde, cuminaldehyde, benzaldehyde, and citronellal. Non-limiting examples of ketones include 1-hydroxy-2-propanone and 2-hydroxy-3-methyl-2-cyclopentenone-1-one. Non-limiting examples of esters include allyl hexanoate, ethyl heptanoate, ethyl hexanoate, isoamyl acetate, and 3-methylbutyl acetate. Non-limiting examples of terpenes include sabinene, limonene, gamma-terpinene, beta-farnesene, nerolidol, thujone, myrcene, geraniol, nerol, citronellol, linalool, and eucalyptol. In one embodiment, the at least one volatile flavor component comprises one or more of ethyl vanillin, cinnamic aldehyde, sabinene, limonene, gamma-terpinene, beta-farnesene, or citral. In one embodiment, the at least one volatile flavor component comprises ethyl vanillin.

[0185] The amount of flavoring utilized in the mixture may vary, but is typically up to about 10 weight percent, with certain embodiments characterized as having a flavoring content of at least about 0.1 weight percent, e.g., from about 0.5 to about 10 weight percent, from about 1 to about 6 weight percent, or from about 2 to about 5 weight percent, based on the total weight of the mixture.

[0186] The amount of flavoring agent present in the mixture may vary over a period of time (e.g., during the storage period after preparation of the mixture). For example, certain volatile components present in the mixture may undergo evaporation or chemical transformation, which results in a decrease in the concentration of one or more volatile flavoring components. In one embodiment, the concentration of one or more of the at least one volatile flavoring components present is higher than the concentration of one or more volatile flavoring components present in a control pouch product that does not contain one or more organic acids after the same period of time. Without wishing to be bound by theory, it is believed that the same mechanism responsible for the loss of whiteness leads to a slow decrease in certain volatile components in the flavoring fraction (e.g., aldehydes, ketones, terpenes). Thus, it can be expected that the decrease in the presence of these volatile components that lead to discoloration over time will reduce the sensory satisfaction associated with products that are exposed to such degradation processes.

[0187] salt In some embodiments, the mixture may further include a salt (e.g., an alkali metal salt), typically utilized in an amount sufficient to impart desired sensory attributes to the mixture. Non-limiting examples of suitable salts include sodium chloride, potassium chloride, ammonium chloride, flour salts, and the like. When present, representative amounts of salt are about 0.5 weight percent or more, about 1.0 weight percent or more, or about 1.5 weight percent or more, but typically comprise about 10 weight percent or less, or about 7.5 weight percent or less, or about 5 weight percent or less (e.g., about 0.5 to about 5 weight percent) of the total weight of the mixture.

[0188] Sweetener The mixture typically further comprises one or more sweeteners. The sweetener can be any sweetener or combination of sweeteners, in natural or artificial form, or a combination of natural and artificial sweeteners. Examples of natural sweeteners include isomaltulose, fructose, sucrose, glucose, maltose, mannose, galactose, lactose, stevia, honey, and the like. Examples of artificial sweeteners include sucralose, maltodextrin, saccharin, aspartame, acesulfame K, neotame, and the like. In some embodiments, the sweetener comprises one or more sugar alcohols. Sugar alcohols are polyols derived from monosaccharides or disaccharides, having a partially or fully hydrogenated form. Sugar alcohols, for example, have from about 4 to about 20 carbon atoms and include erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and combinations thereof (e.g., hydrogenated starch hydrolysates). When present, a representative amount of sweetener may comprise, on a weight basis, from about 0.1 to about 20 weight percent or more of the mixture, for example, from about 0.1 to about 1 weight percent, from about 1 to about 5 weight percent, from about 5 to about 10 weight percent, or from about 10 to about 20 weight percent of the mixture, based on the total weight of the mixture.

[0189] Binder In certain embodiments, a binder (or combination of binders) can be utilized in an amount sufficient to provide the mixture with the desired physical characteristics and physical integrity. Binders often also function as thickeners or gelling agents. Typical binders can be organic or inorganic, or combinations thereof. Representative binders include modified cellulose, povidone, sodium alginate, starch-based binders, pectin, carrageenan, pullulan, zein, and the like, and combinations thereof. In some embodiments, the binder comprises pectin or carrageenan, or combinations thereof.

[0190] The binder may be utilized in an amount sufficient to provide the mixture with the desired physical characteristics and physical integrity. The amount of binder utilized in the mixture may vary, but is typically up to about 30 weight percent, with certain embodiments characterized by a binder content of at least about 0.1 weight percent, e.g., from about 1 to about 30 weight percent, or from about 5 to about 10 weight percent, based on the total weight of the mixture.

[0191] In certain embodiments, the binder comprises a gum, e.g., a natural gum. As used herein, a natural gum refers to a polysaccharide material of natural origin that has binding properties and is also useful as a thickening or gelling agent. Representative natural gums derived from plants are usually water-soluble to some extent and include xanthan gum, guar gum, gum arabic, gum ghatti, gum tragacanth, gum karya, locust bean gum, gellan gum, and combinations thereof. When present, the natural gum binder material is usually present in an amount of up to about 5% by weight, e.g., from about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, or about 1% to about 2, about 3, about 4, or about 5% by weight, based on the total weight of the mixture.

[0192] Moisturizer In certain embodiments, one or more humectants can be utilized in the mixture. Examples of humectants include, but are not limited to, glycerin, propylene glycol, and the like. When included, the humectant is typically provided in an amount sufficient to provide the mixture with the desired moisture characteristics. Additionally, in some cases, the humectant can impart desirable flow properties to the mixture for deposition into a mold. When present, the humectant typically comprises about 10% or less (e.g., about 0.5 to about 8% by weight) of the mixture. When present, representative amounts of humectant are about 0.1% to about 1% by weight, about 0.1% to about 0.5% by weight, about 1% to about 5% by weight, about 2% to about 10% by weight, or about 5% to about 10% by weight, based on the total weight of the mixture. In some embodiments, the humectant (e.g., glycerol) can improve the flavor release and / or flavor intensity profile of the disclosed products.

[0193] pH adjuster / buffer In certain embodiments, the mixture of the present disclosure can include a pH adjuster or buffer. Examples of pH adjusters and buffers that can be used include, but are not limited to, metal hydroxides (e.g., alkali metal hydroxides, such as sodium hydroxide and potassium hydroxide) and alkaline earth metal hydroxides (e.g., calcium hydroxide and magnesium hydroxide), as well as other alkali metal buffers, such as metal carbonates (e.g., potassium carbonate, calcium carbonate, or sodium carbonate), or metal bicarbonates, such as sodium bicarbonate, potassium bicarbonate, etc. Additional non-limiting examples include ammonia hydroxide, potassium acetate, sodium acetate, sodium benzoate, sodium sesquicarbonate, trisodium phosphate, and combinations thereof. If present, the buffering agent is typically present in an amount of less than about 5 percent by weight of the mixture, e.g., about 0.1% to about 1%, about 0.1% to about 0.5%, or 0.5% to about 5%, e.g., about 0.75% to about 4%, about 0.75% to about 3%, or about 1% to about 2% by weight of the total mixture. Non-limiting examples of suitable buffering agents include alkali metal acetates, glycinates, phosphates, glycerophosphates, citrates, carbonates, bicarbonates, borates, or mixtures thereof.

[0194] Typically, the nicotine complexes present in the disclosed compositions require the inclusion of a base, in certain embodiments a relatively strong base, to release nicotine therefrom. For example, in some embodiments, a pH adjuster is included in the composition that is a stronger base than carbonate. Examples of bases that may be sufficient for this purpose include, but are not limited to, metal hydroxides, such as potassium hydroxide, calcium hydroxide, and sodium hydroxide. Note that in some embodiments, additional buffering / pH adjusters may be included in the disclosed compositions (including, for example, but not limited to, metal carbonates). In some embodiments, such additional components may perform one or more additional functions within the composition (e.g., modifying the flavor of the composition).

[0195] In some embodiments, the pH of compositions within the scope of the present disclosure is about 6-9, e.g., about 6-7, 6-8, 6.5-7, 6.5-8, 6.5-9, 7-8, 7-9, 8-9, or 8.5-9. In some embodiments, low pH values ​​(e.g., less than about 6.5, less than about 6, less than about 5.5, or less than about 5, including, e.g., about 3 to about 7, about 3 to about 6.5, about 3 to about 6, about 4 to about 6.5, about 4 to about 6, etc.) have been found to be beneficial for product stability for nicotine-containing oral products. In particular, in some embodiments, low pH values ​​have been found to provide better flavor stability and nicotine retention over time compared to high pH oral products. pH measurements can be performed, for example, by placing 1.5 g of the composition to be tested (which may be, for example, two pouches) into 30 mL of water. A magnetic stir bar is placed inside the vessel and the mixture is stirred while a pH meter with a glass electrode is used to measure the pH.

[0196] According to the present disclosure, it has been found that pouch products containing compositions containing resin-bound nicotine, such as nicotine polacrilex, demonstrate undesirably low nicotine release percentage from the resin under low pH conditions. Surprisingly, according to the present disclosure, it has been found that increasing the ionic strength of compositions containing resin-bound nicotine can improve the release of nicotine from the resin. For example, in some embodiments, calcium hydroxide is particularly useful as a base / pH adjuster. Without intending to be limited by theory, it is believed that as a strong base with multivalent cations, calcium hydroxide has a better efficiency than, for example, sodium hydroxide in displacing nicotine from the resin. Furthermore, in some embodiments, the use of calcium hydroxide can avoid the use of liquid, corrosive sodium hydroxide solution or potassium hydroxide, which provides certain advantages in terms of safety and handling.

[0197] It has also surprisingly been found, according to the present disclosure, that the inclusion of certain organic acids, salts of such organic acids, or combinations thereof, and in particular the choice of counterions thereof, can also improve the release of nicotine from the resin. Without wishing to be bound by any particular theory, it is believed that ion pairing between the resin-bound nicotine and the counterions of the organic acids or salts thereof, either in the composition or during use of the composition, or both, contributes to or results in such improved nicotine release, which may be pH-dependent.

[0198] Coloring agent The coloring agent can be utilized in an amount sufficient to provide the mixture with the desired physical characteristics. Natural or synthetic coloring agents, such as natural or synthetic dyes, food grade coloring agents, and pharmaceutical grade coloring agents can be used. Examples of coloring agents include various dyes and pigments, such as caramel coloring and titanium dioxide. Natural coloring agents, such as curcumin, beet juice extract, spirulina; various synthetic pigments can also be used. In some embodiments, the coloring agent is a lake dye, such as red or blue aluminum lake dye. The amount of coloring agent utilized in the oral composition can vary, but when present, is usually up to about 3% by weight, such as from about 0.1%, about 0.5%, or about 1% to about 3% by weight based on the total weight of the oral composition.

[0199] active ingredient In some embodiments, the only active ingredient contained within the disclosed oral products is nicotine (i.e., the referenced nicotine component or first and second nicotine components). However, in some embodiments, the compositions disclosed herein include one or more active ingredients in addition to such nicotine component(s).

[0200] As used herein, "active ingredient" refers to one or more substances that belong to any of the following categories: APIs (active pharmaceutical ingredients), food additives, natural drugs, and naturally derived substances that may have an effect on humans. Exemplary active ingredients that may be used in addition to the nicotine component(s) include any ingredient known to affect one or more biological functions in the body, such as ingredients that provide pharmacological activity or other direct effects in the diagnosis, cure, mitigation, treatment, or prevention of disease, or that affect the structure or any function of the human body (e.g., provide a stimulating effect on the central nervous system, have an energizing, antipyretic or analgesic effect, or have other effects that are beneficial to the body). In some embodiments, the optional additional active ingredient may be of the type commonly referred to as a dietary supplement, nutraceutical, "phytochemical agent," or "functional food." These types of additives may also be defined in the art to include substances that provide one or more beneficial biological effects (e.g., health promotion, disease prevention, or other pharmacological effects), but are normally available from naturally derived sources (e.g., botanical materials) that are not classified or regulated as drugs.

[0201] Non-limiting examples of additional active ingredients include those falling into the categories of botanical ingredients, stimulants, amino acids, and / or pharmaceutical, nutraceutical and medicinal ingredients (e.g., vitamins such as A, B3, B6, B12, and C, and / or cannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD)). Each of these categories is further described herein below. If used, the particular choice of additional active ingredients will depend on the desired flavor, texture, and desired characteristics of the particular product.

[0202] In certain embodiments, the additional active ingredient is selected from the group consisting of caffeine, taurine, GABA, theanine, vitamin C, lemon balm extract, ginseng, citicoline, sunflower lecithin, and combinations thereof. For example, the active ingredient can include a combination of caffeine, theanine, and optionally ginseng. In another embodiment, the active ingredient includes a combination of theanine, gamma-aminobutyric acid (GABA), and lemon balm extract. In a further embodiment, the active ingredient includes theanine, theanine and tryptophan, or theanine and one or more B vitamins (e.g., vitamin B6 or B12). In yet a further embodiment, the active ingredient includes a combination of caffeine, taurine, and vitamin C.

[0203] The specific percentage of additional active ingredients present will vary depending on the desired characteristics of a particular product. If present, such additional active ingredients or combinations thereof are usually included at a total concentration of at least about 0.001% by weight of the composition, for example, in the range of about 0.001% to about 20%. In some embodiments, if present, the optional additional active ingredient or combination of active ingredients is present at a concentration of about 0.1% w / w to about 10% by weight, for example, about 0.5% w / w to about 10%, about 1% to about 10%, about 1% to about 5% by weight, based on the total weight of the composition. In some embodiments, if present, the additional active ingredient or combination of active ingredients may be present in an amount of from about 0.001%, about 0.01%, about 0.1%, or about 1% up to about 20% by weight, for example, about 0.001%, about 0.002%, about 0.003%, about 0.004%, about 0.005%, about 0.006%, about 0.007%, about 0.008%, about 0.009%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0. In some embodiments, the active ingredient may be present in a concentration of about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, or about 0.9% to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20% by weight. In some embodiments, further suitable ranges for specific active ingredients that may be utilized in combination with the above-referenced nicotine component(s) are provided herein below.

[0204] Botanical In some embodiments, the active ingredient comprises a botanical ingredient. As used herein, the term "botanical ingredient" or "botanical" refers to any plant material or fungus-derived material (including plant material in its natural form) and plant material derived from natural plant material, such as an extract or isolate from a plant material or a processed plant material (e.g., a plant material that has been subjected to a heat treatment, fermentation, bleaching, or other treatment process that can modify the physical and / or chemical properties of the material). For purposes of this disclosure, "botanical" includes, but is not limited to, "herbal materials," which refer to seed-producing plants that do not produce persistent woody tissue and are often valued for their medicinal or sensory properties (e.g., tea or herbal tea). Reference to a botanical material as "non-tobacco" is intended to exclude tobacco materials (i.e., does not include any Nicotiana species). In some embodiments, the compositions disclosed herein can be characterized as being free of any tobacco materials (e.g., any embodiment disclosed herein may be completely or substantially free of any tobacco materials). By "substantially free" it is meant that no tobacco material has been intentionally added. For example, certain embodiments may be characterized as having less than 0.001% tobacco by weight, or less than 0.0001%, or even 0% tobacco by weight.

[0205] If present, the botanicals will typically be at a concentration of about 0.01% w / w to about 10% by weight, for example, from about 0.01% w / w, about 0.05% w / w, about 0.1% w / w, or about 0.5% w / w, up to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%, about 11%, about 12%, about 13%, about 14%, or about 15% by weight, based on the total weight of the composition.

[0206] Botanical materials useful in the present disclosure can include, without limitation, any of the compounds and sources described herein, including mixtures thereof. Certain botanical materials of this type are sometimes referred to as dietary supplements, nutraceuticals, "phytochemical agents" or "functional foods." Certain botanicals find use in traditional herbal medicines as botanical materials or botanical extracts, and are further described herein.Non-limiting examples of plants or plant-derived materials include ashwagandha, Bacopa monniera, baobab, basil, Centella asiatica, chai fu, chamomile, cherry blossom, chlorophyll, cinnamon, citrus, clove, cocoa, cordyceps, curcumin, damiana, Dorstenia arifolia, Dorstenia odorata, essential oils, eucalyptus, fennel, Galphimia glauca, ginger, Ginkgo biloba, carrots (e.g., Panax ginseng), green tea, Griffonia simplicifolia, and the like. simplicifolia, guarana, hemp, cannabis, hops, jasmine, Kaempferia parviflora (turmeric), kava, lavender, lemon balm, lemongrass, licorice, lutein, maca, matcha, oil-based extract of Nardostachys chinensis, Viola odorata, peppermint, quercetin, resveratrol, Rhizoma gastrodiae, Rhodiola, rooibos, rose essential oil, rosemary, Sceletium tortuosum, Schisandra chinensis, skullcap, spearmint extract, spikenard, terpenes, herbal tea, turmeric, Turnera aphrodisiaca aphrodisiaca), valerian, mulberry and yerba mate.

[0207] In some embodiments, the active ingredient comprises lemon balm. Lemon balm (Melissa officinalis) is a mild lemon-scented herb in the same family as mint (Lamiaceae). The herb is native to Europe, North Africa and Western Asia. Lemon balm teas, as well as essential oils and extracts, are used in traditional and alternative medicines. In some embodiments, the active ingredient comprises lemon balm extract. In some embodiments, the lemon balm extract is present in an amount of about 1 to about 4% by weight, based on the total weight of the composition.

[0208] In some embodiments, the active ingredient comprises ginseng. Ginseng is the root of the Panax plant and is characterized by the presence of unique steroidal saponin phytochemical agents (ginsenosides) and gintonin. Ginseng finds use as a dietary supplement in energy drinks or herbal teas and traditional medicines. Cultivated species include P. ginseng (P. Ginseng), P. notoginseng (P. notoginseng) and P. quinquefolius (P. quinquefolius). American ginseng and P. ginseng differ in the types and amounts of various ginsenosides present. In some embodiments, the ginseng is American ginseng or P. ginseng. In certain embodiments, the active ingredient comprises P. ginseng. In some embodiments, the ginseng is present in an amount of about 0.4 to about 0.6% by weight based on the total weight of the composition.

[0209] Stimulants In some embodiments, the active ingredient comprises one or more stimulants. As used herein, the term "stimulant" refers to a material that increases the activity of the central nervous system and / or the body, for example, enhancing focus, cognition, energy, mood, alertness, etc. Non-limiting examples of stimulants include caffeine, theacrine, theobromine, and theophylline. Theacrine (1,3,7,9-tetramethyluric acid) is a purine alkaloid structurally related to caffeine and has stimulating, analgesic, and anti-inflammatory properties. Stimulants present may be natural, derived from nature, or completely synthetic. For example, certain botanical materials (such as guarana, tea, coffee, cocoa, etc.) may have stimulant properties due to the presence of, for example, caffeine or related alkaloids, and are therefore "natural" stimulants. "Naturally derived" means that the stimulant (e.g., caffeine, theacrine) is in a purified form outside of its natural (e.g., botanical) matrix. For example, caffeine can be obtained by extraction and purification from botanical sources (e.g., tea). "Fully synthetic" means that the stimulant is obtained by chemical synthesis. In some embodiments, the active ingredient comprises caffeine. In some embodiments, the caffeine is present in an encapsulated form. One example of encapsulated caffeine is Vitashure®, available from Balchem ​​Corp., 52 Sunrise Park Road, New Hampton, NY, 10958.

[0210] When present, the stimulant or combination of stimulants (e.g., caffeine, theacrine, and combinations thereof) is typically at a concentration of about 0.1% w / w to about 15% by weight, for example, about 0.1% w / w, about 0.2% w / w, about 0.3% w / w, about 0.4% w / w, about 0.5% w / w, about 0.6% w / w, about 0.7% w / w, about 0.8% w / w, or about 0.9% w / w, to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, or about 15% by weight, based on the total weight of the composition. In some embodiments, the composition comprises caffeine in an amount of about 1.5 to about 6% by weight, based on the total weight of the composition.

[0211] amino acid In some embodiments, the active ingredient comprises an amino acid. As used herein, the term "amino acid" refers to an organic compound containing an amine (-NH2) and a carboxyl (-COOH) or sulfonic acid (SO3H) functional group, with a side chain (R group) that is specific to each amino acid. An amino acid may be proteinogenic or non-proteinogenic. "Proteogenic" means that the amino acid is one of the 20 naturally occurring amino acids found in proteins. Proteinogenic amino acids include alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. "Non-proteinogenic" means that the amino acid is not naturally found in proteins or produced directly by cellular machinery (e.g., is a product of post-translational modification). Non-limiting examples of non-proteinogenic amino acids include gamma-aminobutyric acid (GABA), taurine (2-aminoethanesulfonic acid), theanine (L-gamma-glutamylethylamide), hydroxyproline, and beta-alanine. In some embodiments, the active ingredient comprises theanine. In some embodiments, the active ingredient comprises GABA. In some embodiments, the active ingredient comprises a combination of theanine and GABA. In some embodiments, the active ingredient is a combination of theanine, GABA, and lemon balm. In some embodiments, the active ingredient is a combination of caffeine, theanine, and ginseng. In some embodiments, the active ingredient comprises taurine. In some embodiments, the active ingredient is a combination of caffeine and taurine.

[0212] When present, the amino acid or combination of amino acids (e.g., theanine, GABA, and combinations thereof) will typically be at a concentration of about 0.1% w / w to about 15% by weight, for example, from about 0.1% w / w, about 0.2% w / w, about 0.3% w / w, about 0.4% w / w, about 0.5% w / w about 0.6% w / w, about 0.7% w / w, about 0.8% w / w, or about 0.9% w / w, to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, or about 15% by weight, based on the total weight of the composition.

[0213] vitamin In some embodiments, the active ingredient comprises a vitamin or a combination of vitamins. As used herein, the term "vitamin" refers to an organic molecule (or set of related molecules) that is a major micronutrient required for the proper functioning of metabolism in mammals. Thirteen vitamins are required for human metabolism, and these are as follows: vitamin A (all-trans-retinol, all-trans-retinyl-esters, and all-trans-β-carotene and other provitamin A carotenoids), vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B7 (biotin), vitamin B9 (folic acid or folate), vitamin B12 (cobalamin), vitamin C (ascorbic acid), vitamin D (calciferol), vitamin E (tocopherols and tocotrienols), and vitamin K (quinones). In some embodiments, the active ingredient comprises vitamin C. In some embodiments, the active ingredient is a combination of vitamin C, caffeine and taurine.

[0214] When present, a vitamin or combination of vitamins (e.g., vitamin B6, vitamin B12, vitamin E, vitamin C, or a combination thereof) is typically present in an amount of from about 0.01% w / w to about 6% by weight, for example, about 0.01% w / w, about 0.02% w / w, about 0.03% w / w, about 0.04% w / w, about 0.05% w / w, about 0.06% w / w, based on the total weight of the composition. In some embodiments, the concentration is from about 0.07% w / w, about 0.08% w / w, about 0.09% w / w, or about 0.1% w / w / w, to about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, about 4%, about 5%, or about 6% by weight.

[0215] Antioxidants In some embodiments, the active ingredient comprises one or more antioxidants. As used herein, the term "antioxidant" refers to a substance that prevents or inhibits oxidation by terminating free radical reactions, which can slow or prevent some types of cell damage. Antioxidants can be naturally occurring or synthetic. Naturally occurring antioxidants include those found in foods and botanical materials. Non-limiting examples of antioxidants include certain botanical materials, vitamins, polyphenols, and phenol derivatives.

[0216] Examples of botanical ingredients with antioxidant properties include, without limitation, acai berry, alfalfa, allspice, annatto seed, apricot oil, basil, bee balm, wild bergamot, black pepper, blueberry, borage seed oil, burdock, cacao, calamus root, catnip, catuaba, cayenne pepper, chaga mushroom, chervil, cinnamon, dark chocolate, potato skin, grape seed, carrot, ginkgo biloba, St. John's wort, saw palmetto, green tea, black tea, black cohosh, cayenne, chamomile, cloves, cocoa powder, cranberry, dandelion, grapefruit, honeybush, echinacea, garlic, evening primrose, feverfew, ginger, goldenseal, hawthorn, and hibiscus. flowers, gynostemma, kava, lavender, licorice, origanum, milk thistle, mint, oolong tea, beet root, orange, oregano, papaya, pennyroyal, peppermint, red clover, rooibos (red or green), rose hips, rosemary, sage, clary sage, savory, spearmint, spirulina, slippery elm bark, sorghum bran high tannin, sorghum seed high tannin, sumac bran, comfrey leaf and root, goji berry, gotu kola, thyme, turmeric, uva ursi, valerian, wild yam root, wintergreen, yacon root, yellow dock, yerba mate, yerba santa, bacopa monniera, ashwagandha, yamabushitake and silybum marianum. Such botanical materials may be provided in fresh or dried form, in essential oils, or in the form of extracts. Botanical materials (as well as their extracts) often contain various classes of compounds known to provide antioxidant benefits, such as minerals, vitamins, isoflavones, phytosterols, allyl sulfides, dithiolthiones, isothiocyanates, indoles, lignans, flavonoids, polyphenols, and carotenoids.Examples of compounds found in botanical extracts or oils include ascorbic acid, peanut endocarp, resveratrol, sulforaphane, β-carotene, lycopene, lutein, coenzyme Q, carnitine, quercetin, kaempferol, etc. See, e.g., Santhosh et al., Phytomedicine, vol. 12 (2005) pp. 216-220, incorporated herein by reference.

[0217] Other non-limiting examples of suitable antioxidants include citric acid, vitamin E or a derivative thereof, tocopherol, epicatechol, epigallocatechol, epigallocatechol gallate, erythorbic acid, sodium erythorbate, 4-hexylresorcinol, theaflavin, theaflavin monogallate A or B, theaflavin digallate, phenolic acids, glycosides, quercitrin, isoquercitrin, hyperosides, polyphenols, catechol, resveratrol, oleuropein, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tertiary butylhydroquinone (TBHQ), and combinations thereof.

[0218] When present, the antioxidant is typically at a concentration of about 0.001% w / w to about 10% by weight, for example, from about 0.001% w / w, about 0.005% w / w, about 0.01% w / w / w, about 0.05% w / w, about 0.1% w / w, or about 0.5% w / w, to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% by weight, based on the total weight of the composition.

[0219] Cannabinoids In some embodiments, the active ingredient comprises one or more cannabinoids.As used herein, the term "cannabinoid" refers to a class of diverse chemical compounds that act on cannabinoid receptors, also known as the endocannabinoid system in cells, to change neurotransmitter release in the brain.The ligands for these receptor proteins include the endocannabinoids that are naturally produced in the body by animals; the phytocannabinoids found in cannabis; and the synthetic cannabinoids that are artificially produced. Cannabinoids found in cannabis include, without limitation, cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), thrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabinotriol (CBO), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabivarinic acid (THCV A). In certain embodiments, the cannabinoid is selected from tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, and cannabidiol (CBD), another major component of the plant, which does not contain psychoactive properties. All of the above compounds can be used in the form of isolates from plant material or synthetically derived forms.

[0220] Alternatively, the active ingredient can be a cannabis analogue, which is a class of compounds derived from plants other than cannabis that have biological effects on the endocannabinoid system similar to cannabinoids. Examples include yangonin, alpha-amyrin or beta-amyrin (also classified as terpenes), cyanidin, curcumin (turmeric), catechin, quercetin, salvinorin A, N-acylethanolamines, and N-alkylamide lipids.

[0221] If present, the cannabinoid (e.g., CBD) or cannabis analogue will typically be at a concentration of at least about 0.1% by weight of the composition, for example, in the range of about 0.1% to about 30% by weight, for example, from about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, or about 0.9% by weight, up to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 15%, about 20%, or about 30% by weight, based on the total weight of the composition.

[0222] Terpenes Active ingredients suitable for use in the present disclosure can also be classified as terpenes, many of which are associated with biological effects, such as sedative effects. Terpenes have the general formula (C5H8): n Terpenes are believed to have the formula: and include monoterpenes, sesquiterpenes, and diterpenes. Terpenes can be acyclic, monocyclic, or bicyclic structures. Some terpenes provide an entourage effect when used in combination with cannabinoids or cannabis analogues. Examples include beta-caryophyllene, linalool, limonene, beta-citronellol, linalyl acetate, pinene (alpha or beta), geraniol, carvone, eucalyptol, menthone, iso-menthone, piperitone, myrcene, beta-bourbonene, and germacrene, which can be used individually or in combination.

[0223] Pharmaceutical Ingredients In some embodiments, the active ingredient comprises an active pharmaceutical ingredient (API). APIs can be any known pharmaceutical agent adapted for therapeutic, prophylactic or diagnostic use. These can include, for example, synthetic organic compounds, proteins and peptides, polysaccharides and other sugars, lipids, phospholipids, inorganic compounds (e.g., magnesium, selenium, zinc, nitrates), neurotransmitters or their precursors (e.g., serotonin, 5-hydroxytryptophan, oxytriptan, acetylcholine, dopamine, melatonin) and nucleic acid sequences, which have therapeutic, prophylactic or diagnostic activity. Non-limiting examples of APIs include analgesics and antipyretics (e.g., acetylsalicylic acid, acetaminophen, 3-(4-isobutylphenyl)propanoic acid), phosphatidylserine, myo-inositol, docosahexaenoic acid (DHA, omega-3), arachidonic acid (AA, omega-6), S-adenosylmethionine (SAM), beta-hydroxy-beta-methylbutyrate (HMB), citicoline (cytidine-5'-diphosphate-choline), and cotinine. In some embodiments, the active ingredient comprises citicoline. In some embodiments, the active ingredient is a combination of citicoline, caffeine, theanine, and carrot. In some embodiments, the active ingredient comprises sunflower lecithin. In some embodiments, the active ingredient is a combination of sunflower lecithin, caffeine, theanine, and carrot.

[0224] The amount of API may vary. For example, when present, the API is typically present in an amount of from about 0.001% w / w to about 10 w / w%, for example, about 0.01 w / w%, about 0.02 w / w%, about 0.03 w / w%, about 0.04 w / w%, about 0.05 w / w%, about 0.06 w / w%, about 0.07 w / w%, about 0.08 w / w%, about 0.09 w / w%, about 0.1% w / w, about The concentrations are from about 0.2 w / w%, about 0.3 w / w%, about 0.4 w / w%, about 0.5 w / w%, about 0.6 w / w%, about 0.7 w / w%, about 0.8 w / w%, about 0.9 w / w%, or about 1 w / w%, up to about 2 w / w%, about 3 w / w%, about 4 w / w%, about 5 w / w%, about 6 w / w%, about 7 w / w%, about 8 w / w%, about 9 w / w%, or about 10% by weight.

[0225] In some embodiments, the composition is substantially free of any API. By "substantially free of any API" is meant that the composition does not contain, and selectively excludes, the presence of any API as defined herein, e.g., any Food and Drug Administration (FDA) approved therapeutic agent intended to treat any medical condition.

[0226] Tobacco Materials In some embodiments, the mixture can include tobacco material. The tobacco material can vary in species, variety, and form. Typically, the tobacco material is obtained from harvested plants of Nicotiana species. Exemplary Nicotiana species include N. tabacum, N. rustica, N. alata, N. arentsii, N. excelsior, N. forgetiana, N. glauca, N. glutinosa, N. gossei, N. kawakami, N. kawakamii, N. kawakamiii ... akamii, N. knightiana, N. langsdorffi, N. otophora, N. setchelli, N. sylvestris, N. tomentosa, N. tomentosiformis, N. undulata, Nx sanderae sanderae, N. africana, N. amplexicaulis, N. benavidesii, N. bonariensis, N. debneyi, N. longiflora, N. maritina, N. megalosiphon, N. occidentalis, N. paniculata, N. plumbagii N. plumbaginifolia, N. raimondii, N. rosulata, N. simulans, N. stocktonii, N. suaveolens, N. umbratica, N. velutina, N. wigandioides, N. acaulis, N. acuminata, N. attenuata.attenuata, N. benthamiana, N. cavicola, N. clevelandii, N. cordifolia, N. corymbosa, N. fragrans, N. goodspeedii, N. linearis, N. miersii, N. nudicaulis, N. obtusifolia, N. occidentalis subsp. hesperis subsp. Hersperis, N. pauciflora, N. petunioides, N. quadrivalvis, N. repanda, N. rotundifolia, N. solanifolia and N. spegazzinii. Various other representative species of plants of the Nicotiana species are described in Goodspeed, The Genus Nicotiana, (Chonica Botanica) (1954); U.S. Patent No. 4,660,577 to Sensabaugh, Jr. et al.; U.S. Patent No. 5,387,416 to White et al.; U.S. Patent No. 7,025,066 to Lawson et al.; U.S. Patent No. 7,798,153 to Lawrence, Jr., and U.S. Patent No. 8,186,360 to Marshall et al., each of which is incorporated herein by reference. Descriptions of various tobacco varieties, cultivation practices, and harvesting practices are described in Tobacco Production, Chemistry and Technology, Davis et al. (eds.) (1999), which is incorporated herein by reference.

[0227] Nicotiana species from which suitable tobacco material can be obtained can be derived using genetic modification or cross-breeding techniques (e.g., tobacco plants can be genetically engineered or cross-bred to increase or decrease the production of a component, characteristic or trait). See, for example, the types of genetic modifications of plants described in U.S. Patent No. 5,539,093 to Fitzmaurice et al.; U.S. Patent No. 5,668,295 to Wahab et al.; U.S. Patent No. 5,705,624 to Fitzmaurice et al.; U.S. Patent No. 5,844,119 to Weigl; U.S. Patent No. 6,730,832 to Dominguez et al.; U.S. Patent No. 7,173,170 to Liu et al.; U.S. Patent No. 7,208,659 to Colliver et al. and U.S. Patent No. 7,230,160 to Benning et al.; U.S. Patent Application Publication No. 2006 / 0236434 to Conkling et al.; and PCT WO2008 / 103935 to Nielsen et al. See also the types of cigarettes described in U.S. Pat. No. 4,660,577 to Sensabaugh, Jr. et al.; U.S. Pat. No. 5,387,416 to White et al.; and U.S. Pat. No. 6,730,832 to Dominguez et al., each of which is incorporated herein by reference.

[0228] In some embodiments, Nicotiana species can be selected for the content of various compounds present therein. For example, plants can be selected based on being plants that produce relatively large amounts of one or more compounds that one wishes to isolate. In certain embodiments, Nicotiana species plants (e.g., Nicotiana galpaocomun) are specifically cultivated for their abundance of these foliar compounds. Tobacco plants can be grown in greenhouses, growth chambers, or outdoor fields, or grown hydroponically.

[0229] Various parts or portions of a plant of the Nicotiana species may be included in the mixtures disclosed herein. For example, substantially all of the plant (e.g., the whole plant) may be harvested and utilized as is. Alternatively, various parts or pieces of the plant may be harvested or separated for further use after harvest. For example, flowers, leaves, stems, stems, roots, seeds, and various combinations thereof may be isolated for further use or processing. In some embodiments, the tobacco material comprises tobacco leaves (lamina). The mixtures disclosed herein may include processed tobacco parts or pieces, dry processed and aged tobacco in essentially natural lamina and / or stem form, tobacco extracts, extracted tobacco pulp (e.g., using water as a solvent), or mixtures of the foregoing (e.g., mixtures of extracted tobacco pulp that is granulated, dry processed, and combined with aged natural tobacco lamina).

[0230] In certain embodiments, the tobacco material comprises a solid tobacco material selected from the group consisting of lamina and stem. The tobacco used in the mixture most preferably comprises tobacco lamina or a mixture of tobacco lamina and stem, at least a portion of which is smoked. A portion of the tobacco in the mixture may have a processed form, such as processed tobacco stems (e.g., cut rolled stems, cut rolled expanded stems, or cut puff stems), or volume-expanded tobacco (e.g., puffed tobacco, e.g., dry ice expanded tobacco (DIET)). See, for example, the tobacco expansion processes described in U.S. Patent No. 4,340,073 to de la Burde et al.; U.S. Patent No. 5,259,403 to Guy et al.; and U.S. Patent No. 5,908,032 to Poindexter et al.; and U.S. Patent No. 7,556,047 to Poindexter et al., all of which are incorporated by reference. In addition, the mixture may incorporate tobacco that is optionally fermentable. See the types of tobacco processing techniques described in Atchley et al., PCT WO2005 / 063060, which is incorporated herein by reference.

[0231] Tobacco materials are typically used in a form that can be described as particulate (i.e., shredded, milled, granulated, or powdered form). The manner in which tobacco materials are provided in finely divided or powdered form types can vary. Preferably, plant parts or pieces are pulverized, milled, or pulverized into particulate form using equipment and techniques for milling, milling, and the like. Most preferably, the plant material is in a relatively dry form during milling or milling using equipment such as hammer mills, cutter heads, air controlled mills, and the like. For example, tobacco parts or pieces can be milled or milled when their moisture content is less than about 15 weight percent or less than about 5 weight percent. Most preferably, tobacco materials are utilized in the form of parts or pieces having an average particle size between 1.4 millimeters and 250 microns. In some cases, the tobacco particles can be sized to pass a screen mesh to obtain the required particle size range. If desired, air classification equipment can be used to ensure collection of small sized tobacco particles of the desired size or size range. If desired, different size pieces of granulated tobacco can be mixed together.

[0232] The manner in which tobacco is provided in finely divided or powder-type form may vary. Preferably, tobacco parts or pieces are pulverized, milled, or pulverized into a powder-type form using equipment and techniques for milling, milling, and the like. Most preferably, the tobacco is in a relatively dry form during milling or milling using equipment such as hammer mills, cutter heads, air-controlled mills, and the like. For example, tobacco parts or pieces can be milled or milled when their moisture content is less than about 15 weight percent to less than about 5 weight percent. For example, tobacco plants or portions thereof can be separated into individual parts or pieces (e.g., leaves can be removed from the stems, and / or stems and leaves can be removed from the trunks). Harvested plants or individual parts or pieces can be further subdivided into parts or pieces (e.g., leaves can be chopped, cut, powdered, pulverized, milled, or milled into pieces or portions, which pieces or portions can be characterized as filler-type pieces, granules, granular, or fine powders). The plant, or a portion thereof, can be subjected to an external force or pressure (e.g., by pressing or rolling). When such processing conditions are performed, the plant or a portion thereof can have a moisture content that approximates its natural moisture content (e.g., its moisture content immediately after harvesting), a moisture content achieved by adding moisture to the plant or a portion thereof, or a moisture content resulting from drying the plant or a portion thereof. For example, powdered, pulverized, milled, or milled pieces of a plant or a portion thereof can have a moisture content of less than about 25 weight percent, often less than about 20 weight percent, and frequently less than about 15 weight percent.

[0233] For the preparation of oral products, it is common to subject harvested plants of Nicotiana species to a curing process. The tobacco materials incorporated into the mixture for inclusion in the products disclosed herein are appropriately cured and / or aged. Descriptions of different types of curing processes for different types of tobacco are provided in Tobacco Production, Chemistry and Technology, Davis et al. (eds.) (1999). Examples of techniques and conditions for curing flue-cured tobacco are provided in Nestor et al., Beitrage Tabakforsch.Int., Vol. 20, pp. 467-475 (2003) and U.S. Patent No. 6,895,974 to Peele, which are incorporated herein by reference. Exemplary techniques and conditions for air-curing tobacco are described in U.S. Patent No. 7,650,892 to Groves et al.; Roton et al., Beitrage Tabakforsch. Int., Vol. 21, pp. 305-320 (2005) and Staaf et al., Beitrage Tabakforsch. Int., Vol. 21, pp. 321-330 (2005), which are incorporated herein by reference. Certain types of tobacco may also be subjected to alternative types of air-curing processes, such as flame curing or sun curing.

[0234] In certain embodiments, tobacco materials that may be utilized include flue-cured or Virginia (e.g., K326), Burley, sun-cured (e.g., Indian Kurnool and Oriental tobaccos, including Katerini, Pre-Rip, Komotini, Xanthi, and Yambol tobaccos), Maryland, dark, dark-fired, dark air-cured (e.g., Madol, Pasanda, Cubano, Jatin, and Bezuki tobaccos), light air-cured (e.g., North Wisconsin and Galpao tobaccos), Indian air-cured, Red Russian, and Rustica tobaccos, as well as various other rare or specialty tobaccos and various blends of any of the aforementioned tobaccos.

[0235] The tobacco material can also have a so-called "blend" form. For example, the tobacco material can include a mixture of flue-cured, burley (e.g., Malawi Burley) and oriental tobacco parts or pieces (e.g., tobacco composed of or derived from tobacco lamina, or a mixture of tobacco lamina and tobacco stem). For example, a representative blend can incorporate, on a dry weight basis, about 30 to about 70 parts burley tobacco (e.g., lamina, or lamina and stem), and about 30 to about 70 parts flue-cured tobacco (e.g., stem, lamina, or lamina and stem). Other exemplary tobacco blends incorporate, on a dry weight basis, about 75 parts flue-cured tobacco, about 15 parts burley tobacco, and about 10 parts oriental tobacco; or about 65 parts flue-cured tobacco, about 25 parts burley tobacco, and about 10 parts oriental tobacco; or about 65 parts flue-cured tobacco, about 10 parts burley tobacco, and about 25 parts oriental tobacco. Other exemplary tobacco blends incorporate, on a dry weight basis, from about 20 to about 30 parts Oriental tobacco and from about 70 to about 80 parts flue-cured tobacco.

[0236] The tobacco material used in the present disclosure can be subjected to, for example, fermentation, bleaching, etc. If desired, the tobacco material can also be subjected to, for example, irradiation, pasteurization, or otherwise controlled heat treatment. Such treatment processes are detailed, for example, in U.S. Patent No. 8,061,362 to Mua et al., which is incorporated herein by reference. In certain embodiments, the tobacco material can be treated with water and an additive capable of inhibiting the reaction of asparagine to form acrylamide upon heating of the tobacco material (e.g., an additive selected from the group consisting of lysine, glycine, histidine, alanine, methionine, cysteine, glutamic acid, aspartic acid, proline, phenylalanine, valine, arginine, compositions incorporating divalent and trivalent cations, asparaginase, certain non-reducing sugars, certain reducing agents, phenolic compounds, certain compounds having at least one free thiol group or functional group, oxidizing agents, oxidation catalysts, natural plant extracts (e.g., rosemary extract), and combinations thereof). See, for example, the types of treatment processes described in U.S. Patent Publication Nos. 8,434,496, 8,944,072, and 8,991,403 to Chen et al., all of which are incorporated herein by reference. In certain embodiments, this type of treatment is useful when the original tobacco material is subjected to heat in the previously described processes.

[0237] In some embodiments, a type of tobacco material is first selected that is somewhat lighter in color than other tobacco materials when visually inspected (e.g., whitened or bleached). In certain embodiments, the tobacco pulp can be whitened by any means known in the art. For example, bleached tobacco materials produced by various whitening methods using various bleaching or oxidizing agents and oxidation catalysts can be used. Exemplary oxidizing agents include peroxides (e.g., hydrogen peroxide), chlorites, chlorates, perchlorates, hypochlorites, ozone, ammonia, potassium permanganate, and combinations thereof. Exemplary oxidation catalysts are titanium dioxide, manganese dioxide, and combinations thereof.Processes for treating tobacco with bleaching agents are described, for example, in U.S. Pat. No. 787,611 to Daniels, Jr.; U.S. Pat. No. 1,086,306 to Oelenheinz; U.S. Pat. No. 1,437,095 to Delling; U.S. Pat. No. 1,757,477 to Rosenhoch; U.S. Pat. No. 2,122,421 to Hawkinson; U.S. Pat. No. 2,148,147 to Baier; U.S. Pat. No. 2,170,107 to Baier; U.S. Pat. No. 2,274,649 to Baier; U.S. Pat. No. 2,770,239 to Pratz et al., all of which are incorporated herein by reference. No. 3,612,065 to Rosen; U.S. Patent No. 3,851,653 to Rosen; U.S. Patent No. 3,889,689 to Rosen; U.S. Patent No. 3,943,940 to Minami; U.S. Patent No. 3,943,945 to Rosen; U.S. Patent No. 4,143,666 to Rainer; U.S. Patent No. 4,194,514 to Campbell; U.S. Patent Nos. 4,366,823, 4,366,824, and 4,388,933 to Rainer et al.; U.S. Patent No. 4,641,667 to Schmekel et al.; U.S. Patent No. 5,713,376 to Berger; Byrd No. 9,339,058 to Byrd Jr. et al.; U.S. Pat. No. 9,420,825 to Beeson et al.; and U.S. Pat. No. 9,950,858 to Byrd Jr. et al.; as well as U.S. Patent Application Publication No. 2012 / 0067361 to Bjorkholm et al.; U.S. Patent Application Publication No. 2016 / 0073686 to Crooks; U.S. Patent Application Publication No. 2017 / 0020183 to Bjorkholm; and U.S. Patent Application Publication No. 2017 / 0112183 to Bjorkholm, as well as PCT Published Application No. WO1996 / 031255 to Giolvas and PCT Published Application No. WO2018 / 083114 to Bjorkholm.

[0238] In some embodiments, the whitened tobacco material can have an ISO brightness of at least about 50%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, or at least about 80%. In some embodiments, the whitened tobacco material can have an ISO brightness ranging from about 50% to about 90%, from about 55% to about 75%, or from about 60% to about 70%. ISO brightness can be measured according to ISO 3688:1999 or ISO 2470-1:2016.

[0239] In some embodiments, whitened tobacco materials can be characterized by a lightened color (e.g., "whitened") as compared to untreated tobacco materials. White color is often defined with reference to the International Commission on Illumination (CIE) chromaticity diagram. In certain embodiments, whitened tobacco materials can be characterized as being closer to pure white on the chromaticity diagram than untreated tobacco materials.

[0240] Typical inclusion ranges for tobacco material may vary depending on the nature and type of tobacco material and the intended effect of the final mixture, with exemplary ranges being up to about 30% (or up to about 20% or up to about 10% or up to about 5%) by weight of the total edible mixture (e.g., about 0.1 to about 15%). In some embodiments, the tobacco material (e.g., whitened tobacco material) is present in relatively small amounts (e.g., about 0.01% to about 0.1%).

[0241] In some embodiments, the products of the present disclosure may be characterized as being completely free or substantially free of tobacco material (other than purified nicotine as the active ingredient). For example, certain embodiments may be characterized as having less than 1% by weight of tobacco material, 0.5% or less, 0.1% or less, or 0% by weight of tobacco material.

[0242] Other Additives Other additives may be included in the disclosed mixtures. For example, the mixtures may be processed, blended, formulated, combined, and / or mixed with other materials or ingredients. The additives may be artificial or may be obtained or derived from herbal or biological sources. Examples of further types of additives include thickening or gelling agents (e.g., fish gelatin), emulsifiers, oral care additives (e.g., thyme oil, eucalyptus oil, and zinc), preservatives (e.g., potassium sorbate, etc.), zinc or magnesium salts selected for their relative water solubility (e.g., magnesium gluconate or zinc gluconate) for compositions with high water solubility or for compositions with low water solubility (e.g., magnesium oxide or zinc oxide) for their relative water insolubility, disintegration aids, or combinations thereof. See, for example, representative components, combinations of components, relative amounts of the components, and modes and methods for utilizing the components, as described in U.S. Patent No. 9,237,769 to Mua et al., U.S. Patent No. 7,861,728 to Holton, Jr. et al., U.S. Patent Application Publication No. 2010 / 0291245 to Gao et al., and U.S. Patent Application Publication No. 2007 / 0062549 to Holton, Jr. et al., each of which is incorporated herein by reference. Typical inclusion ranges for such additional additives may vary depending on the nature and function of the additive and its intended effect on the final mixture, with exemplary ranges being up to about 10% by weight (e.g., from about 0.1 to about 5% by weight) based on the total weight of the mixture.

[0243] The above-mentioned additives can be utilized together (e.g., as an additive blend) or separately (e.g., individual additive components can be added at different stages involved in the preparation of the final mixture). Furthermore, the above-mentioned types of additives can be encapsulated as provided in the final product or mixture. Exemplary encapsulated additives are described, for example, in WO2010 / 132444 to Atchley, previously incorporated herein by reference.

[0244] In some specific embodiments, the disclosed compositions can include (in addition to the nicotine component(s) described), a filler component (e.g., MCC), a base (e.g., NaOH), a sweetener (e.g., xylitol, sucralose, and / or acesulfame K, etc.), a salt, and a flavoring agent. In some embodiments, the composition includes, based on the total weight of all compositions within the pouch product, 0% to about 1.5% free base nicotine; about 2% to about 8% by weight of a nicotine polymer complex (e.g., containing 20% ​​nicotine); about 3% to about 6% by weight of a base; about 2% to about 8% by weight of a salt, 30% to about 50% by weight of a filler, about 1% to about 5% by weight of a sweetener, and about 0.5% to about 2.5% by weight of a flavoring agent, including additional water that is sprayed onto the pouch product after pouching, as further described herein below.

[0245] In general, the products of the present disclosure can have widely different nicotine release rates. In some embodiments, the pH of the composition can affect the release rate of nicotine from the nicotine polymer complex. Dissolution and counterions determine that pH affects the extraction of nicotine from the resin. For example, decreasing the pH of the composition can slow down the release of nicotine therefrom. However, the inclusion of certain alkali metal or alkaline earth metal salts referred to herein above can enhance the release of nicotine from the resin even at low pH values.

[0246] In some embodiments, as described above, the inclusion of two nicotine components in some embodiments can provide two different release rates of nicotine from a given product in the oral cavity. For example, a first nicotine component (which can provide a somewhat immediate or fast release) can be released more quickly than a second nicotine component (which can provide a more sustained release of nicotine). In some embodiments, nicotine is released from the disclosed compositions / products in the user's oral cavity over a period of at least about 30 minutes, at least about 40 minutes, at least about 45 minutes, at least about 50 minutes, at least about 55 minutes, or at least about 60 minutes, such as from about 30 minutes to about 120 minutes, from about 30 minutes to about 90 minutes, from about 30 minutes to about 60 minutes, from about 40 minutes to about 120 minutes, from about 40 minutes to about 90 minutes, from about 40 minutes to about 60 minutes, from about 45 minutes to about 120 minutes, from about 45 minutes to about 90 minutes, from about 45 minutes to about 60 minutes, from about 50 minutes to about 120 minutes, from about 50 minutes to about 120 minutes, from about 50 minutes to about 90 minutes, from about 50 minutes to about 80 minutes, or from about 50 minutes to about 70 minutes. In some embodiments, about 80% of the nicotine is released from the pouch product after 90 minutes of use.

[0247] The moisture content of the products provided herein can vary. In some embodiments, the moisture content of the disclosed pouch products is greater than about 5% by weight, e.g., about 5% to about 50% by weight. In some embodiments, the moisture content of the disclosed pouch products is about 48% or less, including, e.g., about 5% to about 48%. In some embodiments, the products have a moisture content of greater than about 15% by weight, greater than about 20% by weight, greater than about 25% by weight, greater than about 30% by weight, or greater than about 40% by weight, based on the total pouch product. Some specific examples of total water content according to certain embodiments include about 5% to about 50%, about 5 to about 48%, about 10% to about 50%, about 10% to about 48%, about 15% to about 50%, about 15% to about 48%, about 25% to about 35%, about 25% to about 50%, about 25% to about 48%, about 30% to about 50%, about 30% to about 48%, about 30% to about 35%, about 40% to about 50%, about 40% to about 48%, about 45% to about 50%, or about 45% to about 48% by weight. Such total water content includes, for example, water in the composition within the pouched composition and additional water added to the product, for example, additional water sprayed on the outside of the product after pouching.

[0248] In some embodiments, any one or more of the filler components, tobacco materials, and all of the oral products described herein may be described as particulate materials. As used herein, the term "particulate" refers to a material in the form of a plurality of individual particles, some of which may be in the form of an agglomeration of a plurality of particles, the particles having an average length to width ratio of less than 2:1, such as less than 1.5:1, for example less than about 1:1. In various embodiments, the particles of the particulate material may be described as being substantially spherical or granular.

[0249] Composition / Product Preparation The manner in which the various components of the mixture are combined can vary. Thus, the overall mixture having the various components, e.g., the components of a powdered mixture, can be of a relatively homogenous nature. The components mentioned above can be in liquid or dry solid form and can be blended in a pre-processing step prior to mixing with any remaining components of the mixture, or can simply be mixed together with all other liquid or dry components.

[0250] In some embodiments, the nicotine component / first nicotine component (i.e., nicotine polymer complex) may not be water-soluble. Thus, in some such embodiments, the order of mixing may be important. In certain embodiments, the composition is provided as follows: Dry ingredients including the filler and the first nicotine component (i.e., nicotine polymer complex) are combined to obtain a dry phase. Wet ingredients including the second nicotine component (e.g., in the form of an aqueous solution) and a flavoring are separately combined to obtain a liquid phase. Additional ingredients, e.g., sweeteners, are added to the liquid phase. The dry and liquid phases are mixed. For example, a base is added to the mixture while blending. Additional water is typically added to the pouch during pouching to achieve the desired moisture, as mentioned herein below.

[0251] The various components of the pouching mixture can be contacted, combined, or mixed together using any mixing technique or device known in the art. Any mixing method that brings the mixture components into intimate contact can be used, such as a mixing device featuring an impeller or other agitating structure. Examples of mixing devices include casing drums, conditioning cylinders or drums, liquid spray devices, conical type blenders, ribbon blenders, mixers available from Littleford Day, Inc., such as FKM130, FKM600, FKM1200, FKM2000, and FKM3000, Plough Share type mixer cylinders, Hobart mixers, and the like. Also see, for example, the types of methodologies described in U.S. Patent No. 4,148,325 to Solomon et al.; U.S. Patent No. 6,510,855 to Korte et al.; and U.S. Patent No. 6,834,654 to Williams, each of which is incorporated herein by reference. In some embodiments, the components that form the mixture are prepared so that the mixture can be used in starch molding process to form the mixture.The manner and method of formulating the mixture are clear to those skilled in the art.See, for example, the type of methodology described in U.S. Patent No. 4,148,325 to Solomon et al.; U.S. Patent No. 6,510,855 to Korte et al.; and U.S. Patent No. 6,834,654 to Williams, U.S. Patent No. 4,725,440 to Ridgway et al., and U.S. Patent No. 6,077,524 to Bolder et al., each of which is incorporated herein by reference.

[0252] In various embodiments, a moisture-permeable packet or pouch can act as a container for the use of the composition. For example, the pouch provides a type of liquid-permeable container that can be considered similar in nature to the mesh-type materials used in the construction of tea bags. If desired, flavoring ingredients, disintegration aids, and other desired components can be incorporated into or applied to the pouch material. The composition / structure of such a packet or pouch, such as the container pouch 20 of the embodiment illustrated in FIG. 1, can vary as described herein. For example, suitable packets, pouches, or containers of the type used in the manufacture of smokeless tobacco products can be modified according to the present disclosure and are available under the trade names CatchDry, Ettan, General, Granit, Goteborgs Rape, Grovsnus White, Metropol Kaktus, Mocca Anis, Mocca Mint, Mocca Wintergreen, Kicks, Probe, Prince, Skruf and TreAnkrare. Pouch-type products of similar shape and form to the various embodiments of the pouch products described herein are commercially available as ZONNIC (distributed by Niconovum AB).Furthermore, the pouch-type products are generally similar in shape and form to the various embodiments of the pouch products described as snuff bag compositions E-J in Example 1 of PCT WO2007 / 104573 to Axelsson et al., which are incorporated herein by reference, and which are produced using excipient ingredients and processing conditions that can be used to manufacture the pouch products described herein.

[0253] The pouch can be formed from a fleece material, for example, a fibrous nonwoven web. As used herein, the term "fiber" is defined as the basic element of a textile. Fibers are often in the form of rope-like or thread-like elements. As used herein, the term "fiber" is intended to include fibers, filaments, continuous filaments, staple fibers, and the like. The term "multicomponent fiber" refers to a fiber that contains two or more components with different physical or chemical properties, including bicomponent fibers. Specifically, the term "multicomponent fiber" includes staple and continuous fibers prepared from two or more polymers that exist in separate structured domains within the fiber, as opposed to blends, where the domains tend to be dispersed, random, or unstructured.

[0254] "Fleece material," as used herein, can be formed from various types of fibers (e.g., cellulosic fibers; e.g., viscose fibers, regenerated cellulose fibers, cellulose fibers, and wood pulp; cotton fibers; other natural fibers; or polymer / synthetic type fibers) that can be formed into a conventional woven fleece or other conventional pouch material. For example, the fleece material can be provided in the form of a woven or nonwoven fabric. Suitable types of fleece materials are described, for example, in U.S. Patent No. 8,931,493 to Sebastian et al.; U.S. Patent Application Publication No. 2016 / 0000140 to Sebastian et al.; and U.S. Patent Application Publication No. 2016 / 0073689 to Sebastian et al., all of which are incorporated herein by reference.

[0255] The term "nonwoven" is used herein in reference to a fibrous material, web, mat, batt, or sheet in which the fibers are aligned in an undefined or random direction. Nonwoven fibers are initially presented as unbonded fibers or filaments. A key step in the manufacture of nonwoven fabrics involves bonding the various fibers or filaments together. The manner in which the fibers or filaments are bonded may vary and include thermal, mechanical, and chemical techniques that are selected in part based on the desired characteristics of the final product, as discussed in more detail below.

[0256] In various embodiments, the pouch material can be dissolvable (i.e., ingestible for oral use) such that the pouch material dissolves under normal conditions of use (i.e., upon contact with saliva in the user's mouth). Preferably, the pouch material dissolves after a significant amount of the dissolving components of the composition within the pouch (e.g., active ingredient(s) and / or flavoring agent(s)) have permeated through the pouch material into the user's mouth. For example, the pouch material can be constructed to dissolve at a rate such that the pouch material holds the composition together for a period of time sufficient to allow release of substantially all of the water-soluble components. As described herein, in certain embodiments, the composition within the pouch material can also be dissolvable. In such embodiments, the pouch material can be constructed to dissolve at a rate similar to that at which the composition dissolves. In certain embodiments, the pouch material can be adapted or constructed to at least partially dissolve or completely dissolve in about 5 minutes or more, about 15 minutes or more, about 30 minutes or more, or about 1 hour or more. In certain embodiments, the pouch material can be adapted or constructed to at least partially dissolve or completely dissolve in 30 minutes or more, 45 minutes or more, or 1 hour or more. In some embodiments, the pouch material can be adapted or constructed to at least partially dissolve or completely dissolve in a time period of about 30 seconds to about 30 minutes, about 1 minute to about 25 minutes, about 5 minutes to about 20 minutes, or about 5 minutes to about 15 minutes. Without being limited by theory, pouch products that include dissolvable pouch materials can provide environmental benefits.

[0257] In various embodiments, the dissolvable pouch material may include, but is not limited to, spun or nonwoven alginate fibers, gluten fibers, perforated mini flat sheets derived from alginate, carrageenan and other polymeric binders, and combinations thereof. Without being limited by theory, the dissolution rate of the pouch material may be controlled, for example, by using cross-linking techniques between alginate or pectin and calcium salts. In certain embodiments, the dissolvable pouch material may include fast dissolving fibers formed using an electrospinning process (e.g., solution-based electrospinning) with a hydrophilic polymer. See, for example, the techniques and fibers disclosed in Asawahame, Chawalinee et al., Formation of Orally Fast Dissolving Fibers Containing Propolis by Electrospinning Technique, Chiang Mai J.Sci., 2015, Vol. 42(2), pp. 469-480, which is incorporated herein by reference in its entirety.

[0258] In some embodiments, the fibers in the fleece material can include a polymer selected from the group consisting of, but not limited to, polyglycolic acid, polylactic acid, polyhydroxyalkanoate, polycaprolactone, polybutylene succinate, polybutylene succinate adipate, and copolymers thereof. In some embodiments, the fibers in the fleece material can be selected from the group consisting of wool, cotton, fibers made of cellulosic materials, such as regenerated cellulose, cellulose acetate, cellulose triacetate, cellulose nitrate, ethyl cellulose, cellulose acetate propionate, cellulose acetate butyrate, hydroxypropyl cellulose, methylhydroxypropyl cellulose, protein fibers, and the like. See also the types of fibers described in U.S. Patent Application Publication No. 2014 / 0083438 to Sebastian et al., which is incorporated herein by reference. In various embodiments, the pouch material can include a polymer selected from the group consisting of polyvinylpyrrolidone, polyvinyl alcohol, and combinations thereof.

[0259] Regenerated cellulose fibers (e.g., viscose or lyocell fibers) can be particularly advantageous and are typically prepared by extracting non-cellulosic compounds from wood and contacting the extracted wood with caustic soda, followed by carbon disulfide and then sodium hydroxide to obtain a viscous solution. The solution is then extruded through a spinneret head to create viscous threads of the regenerated fibers. Exemplary methods for the preparation of regenerated cellulose are provided in U.S. Patent No. 4,237,274 to Leoni, U.S. Patent No. 4,268,666 to Baldini et al., U.S. Patent No. 4,252,766 to Baldini et al., U.S. Patent No. 4,388,256 to Ishida et al., U.S. Patent No. 4,535,028 to Yokogi et al., U.S. Patent No. 5,441,689 to Laity, U.S. Patent No. 5,997,790 to Vos et al., and U.S. Patent No. 8,177,938 to Sumnicht, which are incorporated herein by reference. The manner in which regenerated cellulose is made is not limited and can include, for example, both rayon and TENCEL processes. Various manufacturers of regenerated cellulose are known, including Lenzing (Austria), Cordenka (Germany), Aditya Birla (India), and Daicel (Japan).

[0260] The fibers used in the nonwoven webs according to the present disclosure may vary and may include fibers having any type of cross-section, including, but not limited to, circular, rectangular, square, elliptical, triangular, and multilobal. In certain embodiments, the fibers may have one or more void spaces, and the void spaces may have, for example, circular, rectangular, square, elliptical, triangular, or multilobal cross-sections. As previously described, the fibers may be selected from monocomponent (i.e., compositionally uniform throughout the fiber) or multicomponent fiber types, including, but not limited to, fibers having a sheath / core structure or fibers having islands-in-the-sea structure, as well as fibers having side-by-side, segmented pie, segmented cross, segmented ribbon, or multilobal cross-sections with tips.

[0261] The physical parameters of the fibers present in the nonwoven web may vary. For example, the fibers used in the nonwoven web may have different size (e.g., length, dpf) and crimp characteristics. In some embodiments, the fibers used in the nonwoven web may be nanofibers, submicron fibers, and / or micron-sized fibers. In certain embodiments, the fibers of the nonwoven webs useful herein may measure from about 1.5 dpf to about 2.0 dpf, or from about 1.6 dpf to about 1.90 dpf. In preferred embodiments, each fiber may be a staple fiber. Each fiber length may measure, for example, from about 35 mm to about 60 mm, or from about 38 mm to about 55 mm. In various embodiments, each fiber may measure from about 4 to 10 crimps per cm, or from about 5 to 8 crimps per cm. To ensure a preferred blend and directionality of the fibers in the nonwoven web, it may be advantageous for all fibers in the nonwoven web to have similar fiber size and crimp characteristics.

[0262] The fibrous web can have different thicknesses, porosities, and other parameters. The nonwoven web can be formed to retain the composition adapted for oral use enclosed within the outer water permeable pouch, and still allow the consumer to enjoy the flavor of the composition, depending on the fiber orientation and porosity of the pouch product formed from the nonwoven web. For example, in some embodiments, the fibrous web can have a basis weight of about 20 gsm to about 60 gsm, about 20 gsm to about 35 gsm, or about 25 gsm to about 30 gsm. In a preferred embodiment, the fibrous web can have a basis weight of about 28 gsm. The basis weight of the woven fabric can be measured, for example, using ASTM D3776 / D3776M-09a(2013) (Standard Test Methods for Mass Per Unit Area(Weight) of Fabric). In various embodiments, the fibrous web can have a thickness of about 0.1 mm to about 0.15 mm (e.g., about 0.11 mm). The fibrous web can have an elongation of about 70% to about 80%, e.g., about 78%. In some embodiments, the fibrous web can have a peak load of about 4 lbs. to about 8 lbs., e.g., about 5.5 lbs. The elongation and breaking strength of textile fabrics can be measured, for example, using ASTM D5034-09(2013) (Standard Test Method for Breaking Strength and Elongation of Textile Fabrics (Grab Test)). In various embodiments, the fibrous web can have a Tensile Energy Absorption (TEA) of about 35 to about 40, e.g., about 37. In one particular embodiment, the fibrous web can have a Tensile Energy Absorption (TEA) of about 10,000 ml / min / cm. 2The porosity of a textile fabric can be measured, for example, as the force required to break the sample under a tensile load applied per side area of ​​the sample. The porosity, or air permeability, of a textile fabric can be measured, for example, using ASTM D737-04(2012) (Standard Test method for Air Permeability of Textile Fabrics).

[0263] In various embodiments of the pouch products described herein, the outer water-permeable pouch is made from a nonwoven web as described above. In some embodiments, the pouch is constructed of a single layer nonwoven web. In various embodiments, the pouch material comprises a multi-layer composite made of two or more nonwoven layers, each layer being orally ingestible. Each nonwoven layer can be formed by the process discussed below. In the multi-layer structure, the first layer can be relatively hydrophilic and the second layer can be relatively hydrophobic (relative to each other). In some embodiments, the outer water-permeable pouch can comprise an outer hydrophilic layer and an inner hydrophobic layer that can be contacted with the composition adapted for oral use. Thus, the hydrophobic layer can retain any moisture in the composition adapted for oral use during storage of the pouch product, so that the flavoring in the composition is not lost due to moisture loss. However, the capillaries of the hydrophobic layer can allow moisture to escape to the mouth of the user, thereby releasing the flavoring into the oral cavity upon use. In this manner, the pouch material can enhance storage stability without significant compromise to the end user's enjoyment of the product. In a less preferred embodiment, the relatively hydrophilic layer can be located on the inside of the multi-layer structure. The two layers can be formed into a multi-layer composite nonwoven material using any means known in the art, such as by bonding the two layers together using adhesives or stitching. The hydrophobicity of a fibrous material can be evaluated, for example, by measuring the contact angle between a drop of liquid and the surface of the fibrous material, as known in the art.

[0264] In certain embodiments, the pouch material can include a flavoring ingredient (e.g., any of the flavoring ingredients described herein), which can be applied to the nonwoven layer in any conventional manner, such as by coating, printing, etc. In some embodiments of the pouch products described herein, the flavoring in the outer pouch material can be different from the flavoring contained within the composition adapted for oral use. For example, in certain embodiments, the pouch material can have a first flavoring ingredient, and after the pouch material dissolves, more moisture can reach the composition within the pouch material, enhancing the flavoring ingredient within the composition. In this manner, the product can be designed to provide multiple different sensory experiences, i.e., a first sensory experience in which the flavoring of the outer pouch material migrates to the user's mouth, and a second sensory experience in which the flavoring of the inner composition migrates to the user's mouth, which typically occurs at a later time.

[0265] In some embodiments, a heat-sealable binder coating or binder material (e.g., a coating or other additive) can be added to the fibers before, during, or after forming the fleece material. As used herein, "heat-sealable binder coating" refers to a coating material, e.g., an acrylic polymer composition, that is applied to a substrate (e.g., a nonwoven web or fleece material) that allows for sealing of individual pouch seams upon heating. In some embodiments, the binder material can be added to the web fibers before or during lamination of the fibrous webs (i.e., before the fibrous webs are bonded to form the fleece material). In certain embodiments, the binder material can be added to the fleece material after it is formed. In various embodiments, the binder material is in the form of a liquid coating. In certain embodiments, a binder powder can be applied to the fleece material. For example, powdered polyethylene can be used as the binder material. A liquid or powder coating can be applied between the fibrous layers, for example, in cross lamination, air lamination, or after processing. A brief exposure in an oven is sufficient to melt and fuse the binder material.

[0266] The means of producing the nonwoven web may vary. Web formation can be accomplished by any means known in the art. Web formation typically includes a carding step, which involves depositing fibers on a surface followed by longitudinal alignment / blending of the fibers. The fibrous web is then typically subjected to some type of bonding / entanglement, including but not limited to thermal melting or bonding, mechanical entanglement, chemical adhesion, or combinations thereof. In one embodiment, the fibrous web is thermally bonded using a calendar (which can provide flat or point bonding), steam jet bonding, or a ventilated oven. Additional bonding methods include ultrasonic bonding and crimping. In some embodiments, needle punching is utilized, which uses needles to obtain physical entanglement between the fibers. In one embodiment, the web is entangled using a hydroentanglement method, which is a process used to entangle and bond the fibers using hydrodynamic forces. As mentioned above, a binder material can be applied to the fibers of the fibrous web before laminating the fibrous web, during the formation of the fibrous web, and / or after the fibrous web is bonded to form a fleece material. After the fleece material is formed, heat can be applied to the fleece material to activate / at least partially melt the binder material to further bond the fleece material, thus further enhancing the mechanical integrity of the fleece material.

[0267] Methods for forming nonwoven webs containing natural and synthetic fibers can include dry-laid, airlaid and wet-laid methods. In some embodiments, nonwoven fabrics can be formed using spunlaid or spunmelt processes, which include both spunbond and meltblowing processes, and such processes are generally considered to involve melting, extruding, collecting and combining thermoplastic polymeric materials to form fibrous nonwoven webs. Meltblowing technology is known in the art and is discussed in various patents, such as U.S. Patent No. 3,849,241 to Butin, U.S. Patent No. 3,987,185 to Buntin et al., U.S. Patent No. 3,972,759 to Buntin, and U.S. Patent No. 4,622,259 to McAmish et al., each of which is incorporated herein by reference in its entirety. General spunbond processes are described, for example, in U.S. Pat. No. 4,340,563 to Appel et al., U.S. Pat. No. 3,692,618 to Dorschner et al., U.S. Pat. No. 3,802,817 to Matsuki et al., U.S. Pat. Nos. 3,338,992 and 3,341,394 to Kinney et al., U.S. Pat. No. 3,502,763 to Hartmann, and U.S. Pat. No. 303,542,615 to Dobo et al., all of which are incorporated herein by reference.

[0268] In various embodiments, nonwoven webs are made by preparing a dry-laid or spunlaid web of fibers and then needle-punching the web to bond the dry-laid or spunlaid web. A barbed needle is forced through the fibrous web, and the needle-punched fleece material is created when the barbed needle pushes some fibers up or down through the web. When the needle is withdrawn, the fibers punched through the web remain in their new position. This needle-punching process interlocks the fibers, and inter-fiber frictional forces caused by the compression of the web hold the structure together, thereby bonding the web. By moving a sufficient number of fibers within the web, the web is converted into a nonwoven fabric.

[0269] In certain embodiments, the nonwoven web is made by a free carding process with point bonding. Point bonding (e.g., using a calendar) should be limited to a relatively small portion of the surface area of ​​the nonwoven web to maintain good porosity within the web for the migration of water-soluble components through the web during oral use. In certain embodiments, the point bonding is limited to less than about 60% of the surface area of ​​the nonwoven web (or the resulting pouch), such as less than about 50%, less than about 30%, or less than about 20% (e.g., about 1% to about 50%, about 5% to about 40%, or about 10% to about 30%). The advantage of point bonding is the ability to control porosity, flexibility, and fabric strength.

[0270] In other embodiments, the nonwoven web can be subjected to hydroentanglement. The term "hydroentangled" or "spunlaced" as applied to the nonwoven fabrics herein is defined as the web being subjected to impingement by a curtain of high-velocity fine water jets, usually emanating from a nozzle jet strip housed in a pressure vessel, often referred to as a manifold or injector. The hydroentangled fabric can be characterized as reoriented, twisted, rotated, and entangled fibers. For example, the fibers can be hydroentangled by exposing the nonwoven web to hydraulic pressure from one or more hydroentanglement manifolds, at hydraulic pressures ranging from about 10 bar to about 1000 bar. In certain embodiments, compared to point bonding, spunlace technology has a lower impact on the porosity of the web, thereby enhancing the migration of flavorants through the nonwoven pouch material.

[0271] In various embodiments, the nonwoven web can be subjected to a second bonding method to reduce the elongation rate of the web during processing. In certain embodiments, the nonwoven web of the present disclosure can exhibit significant elongation rate during high speed processing on a pouching device. Excessive elongation rate of the nonwoven web can cause the web to shrink during processing, resulting in an end product that is not of the proper size. Thus, for example, it may be necessary to modify the processing equipment to fit a wider roll of fleece to compensate for any shrinkage of the end product due to elongation rate.

[0272] To avoid or at least reduce such elongation problems, in various embodiments, the nonwoven web can be point bonded after the first bonding (e.g., hydroentanglement) is completed. The second bonding process can increase the tensile strength and reduce the elongation characteristics of the nonwoven web. In particular, the point bonding process can bond the nonwoven web by partially or completely melting the web at discrete points (e.g., heat sealable binder material). For example, in some embodiments, the nonwoven web can be subjected to ultrasonic bonding after the initial bonding of the web. Any ultrasonic bonding system known in the art for nonwoven materials can be used to ultrasonically bond the nonwoven web. See, for example, the apparatus and devices disclosed in U.S. Pat. No. 8,096,339 to Aust and U.S. Pat. No. 8,557,071 to Weiler, which are incorporated herein by reference. In some embodiments, the nonwoven web can be subjected to point bonding via embossed and / or engraved calendar rolls, which are typically heated. See, for example, the point bonding methods incorporating the use of very high calendar pressures and embossing techniques discussed in U.S. Patent Publication No. 2008 / 0249492 to Schmidt, which is incorporated by reference herein in its entirety. Point bonding processes are typically limited to less than about 60% of the surface area of ​​the nonwoven web, as discussed above.

[0273] In certain embodiments, the processing techniques used to blend, entangle, and bond the nonwoven web can also impart a desired texture to the fibrous nonwoven web material. For example, point bonding or hydroentanglement can impart a desired texture (e.g., a desired pattern) to the nonwoven web. The texture pattern can include product identifying information. In some embodiments, the product identifying information is selected from the group consisting of product brand, company name, company logo, company brand, marketing message, product strength, active ingredients, product manufacturing date, product expiration date, product flavor, product release profile, weight, product code (e.g., batch code), identification marking with other products, and combinations thereof.

[0274] Various manufacturing equipment and methods can be used to create the pouch products described herein. For example, U.S. Publication No. 2012 / 0055493 to Novak, III et al., which is incorporated by reference in its entirety, relates to an apparatus and process for providing a pouch material formed into a tube for use in the manufacture of smokeless tobacco products. The pouch material can include a binder material (e.g., a binder material including an aliphatic polyester) according to the present disclosure. A similar apparatus incorporating an apparatus for providing a continuous supply of pouch material (e.g., a pouch processing unit adapted to feed the pouch material to a continuous tube forming unit to form a continuous tubular member from the pouch material) can be used to create the pouch products described herein. A representative apparatus for forming a continuous tube of such pouch material is disclosed, for example, in U.S. Patent Application Publication No. 2010 / 0101588 to Boldrini et al., which is incorporated by reference in its entirety. The apparatus further includes a device for supplying a pouch material to the continuous tubular member such that when the continuous tubular member is subdivided and sealed into separate pouch portions, each pouch portion contains a filler material of a composition adapted for oral use. A representative device for supplying a filler material is disclosed, for example, in US Patent Application Publication No. 2010 / 0018539 to Brinkley, which is incorporated herein by reference in its entirety. In some cases, the apparatus may include a subdivision unit for subdividing the continuous tubular member into individual pouch portions, and may include a sealing unit for sealing at least one end of each pouch portion when subdivided into individual pouch portions. In other cases, the continuous tubular member may be sealed by a sealing unit into individual pouch portions, and thus, when the individual pouch portions are sealed, the continuous tubular member may be subdivided into separate individual pouch portions by subdividing the continuous tubular member with a subdivision unit between the sealed ends of the pouch portions arranged in series. In still other cases, sealing (closure) of the individual pouch portions of a continuous tubular member may occur substantially simultaneously with its subdivision using closure and division units.

[0275] An exemplary apparatus for manufacturing oral pouch products is illustrated in Figures 1-5 of U.S. Publication No. 2012 / 0055493 to Novak, III et al. However, this apparatus is used for general and illustrative purposes only and not for limiting purposes. It should also be recognized that the following manufacturing process and associated apparatus are not limited to the process sequence described below. In various embodiments of the present disclosure, an apparatus similar to that described in U.S. Publication No. 2012 / 0055493 can be constructed to removably receive a first bobbin on an unwind spindle assembly, the first bobbin having a continuous length of material, such as pouch material, wound thereon. When the first bobbin engages the apparatus, the pouch material can take a path from the first bobbin toward a forming unit, which is constructed to form a continuous supply of pouch material into a continuous tubular member defining a longitudinal axis.

[0276] Thus, as the pouch material unwinds from the first bobbin, it can be directed around an arrangement of roller members (also referred to herein as dancer assemblies). The forming unit can be constructed to cooperate with the first bobbin and dancer assembly to take up slack in the pouch material and maintain a certain amount of longitudinal tension on the pouch material while the pouch material is unwound from the first bobbin and fed to the forming unit, for example, by a drive system. Those skilled in the art will recognize that between the first bobbin and the forming unit, the pouch material can be supported, routed, and / or guided by any number of appropriately aligned series of, for example, idler rollers, guide posts, air bars, turning bars, guides, tracks, tunnels, etc., for directing the pouch material along a desired path. A typical bobbin used in conventional automated pouch making equipment contains a continuous strip of pouch material that can often vary in length. Thus, the apparatus described herein can be constructed to handle that type and size of bobbins.

[0277] The forming unit can include one or more roller members that are configured to direct the pouch material around the hollow shaft so that a continuous supply of pouch material can be formed into a continuous tubular member. The forming unit can include a sealing device that is configured to seal, secure, or otherwise engage side edges of the pouch material to form a longitudinally extending seam, thereby forming a longitudinally extending continuous tubular member. In various embodiments, the inserting unit can be configured to introduce a filler material of a composition adapted for oral use into the continuous tubular member through the hollow shaft. The inserting unit can be directly or indirectly engaged with the hollow shaft.

[0278] The leading or end (also referred to as the lateral spreading seam) of the continuous tubular member can be closed / sealed such that the filling material of the composition adapted for oral use inserted by the insert unit is contained proximal to the leading end within the continuous tubular member. The leading end can be closed / sealed via a closing and dividing unit that is constructed to close / seal a first portion of the continuous tubular member to form a closed leading end of the pouch member portion. The closing and dividing unit can also be constructed to form a closed trailing edge or end of the leading pouch member portion. In this regard, the closing and dividing unit can also be constructed to close a second portion of the continuous tubular member to form a closed terminal end of the pouch member portion. In this regard, the closing and dividing unit can close the end by heat sealing, or other suitable sealing mechanism.

[0279] As illustrated in Figures 20-22 of U.S. Publication No. 2012 / 0055493 to Novak, III et al., the closure and division unit can be constructed to divide the continuous tubular member into a plurality of separate pouch member portions along the longitudinal axis of the continuous tubular member between the closed ends and closed ends of the serially arranged pouch member portions, such that each separate pouch member portion contains a portion of the oral composition from the insert unit. In this regard, the closure and division unit can include a blade, hot wire, or other cutting arrangement for severing the continuous tubular member into separate pouch member portions. For example, the closure and division unit can include first and second arm members constructed to interact to close and divide the continuous tubular member.

[0280] In operation, fill material of the composition adapted for oral use (i.e., an appropriate amount for an individual pouch member portion) can be delivered by the insert unit to the pouch member portion after the leading end is closed but before the trailing end is closed. In various embodiments, after receiving the fill material of the oral composition, separate individual pouch member portions can be formed by closing the trailing ends and severing the closed pouch member portions from the continuous tubular member to form individual pouch products.

[0281] The amount of material contained in each pouch may vary. In various embodiments, the weight of the mixture in each pouch is at least about 50 mg, e.g., about 50 mg to about 2 grams, about 100 mg to about 1.5 grams, or about 200 mg to about 700 mg. In certain smaller embodiments, the dry weight of the material in each pouch is at least about 50 mg to about 150 mg. For some larger embodiments, the dry weight of the material in each pouch is preferably not more than about 300 mg to about 500 mg. In some embodiments, each pouch / container can have a flavoring member disposed therein, as described in more detail in U.S. Patent No. 7,861,728 to Holton, Jr. et al., which is incorporated herein by reference. For example, at least one flavored strip, piece, or sheet of flavored water-dispersible or water-soluble material (e.g., a breath freshening edible film-type material), with or without at least one capsule, can be disposed in each pouch. Such strips or sheets can be easily incorporated into a pouch by folding or crumpling. See, for example, U.S. Patent No. 6,887,307 to Scott et al. and U.S. Patent No. 6,923,981 to Leung et al., which are incorporated herein by reference; and the types of materials and techniques described in The EFSA Journal (2004) Vol. 85, pp. 1-32. Note that in some embodiments, the fill level is about 75% to about 100%.

[0282] In various embodiments, the nonwoven web can be sufficiently sticky to cause problems with high speed pouch equipment. Thus, in certain embodiments, a Teflon coating, or similar material, can be applied to one or more surfaces of the pouch equipment, such as rollers, cutting equipment, and heat sealing devices, that contact the nonwoven web to reduce and / or mitigate any problems with the pouch material sticking to the pouch equipment during processing.

[0283] The pouch product may further include product identifying information printed or dyed or imprinted (e.g., embossed, debossed, or otherwise pressed) on the outer water-permeable pouch, as described, for example, in U.S. Patent Application Publication No. 2014 / 0255452 to Reddick et al., filed March 11, 2013, which is incorporated herein by reference. As mentioned above, flavorings may also be incorporated into the nonwoven web, if desired, for example, by coating or printing an edible flavoring ink onto the nonwoven web. See, for example, U.S. Patent Application Publication No. 2012 / 0085360 to Kawata et al. and U.S. Patent Application Publication No. 2012 / 0103353 to Sebastian et al., each of which is incorporated herein by reference.

[0284] The disclosed pouch products can be provided in a range of sizes, in some embodiments, the largest dimension (length, e.g., shown as "L" in the example of FIG. 1) is about 16 to about 40 mm, or about 20 to about 40 mm, e.g., about 16 mm, about 17 mm, about 18 mm, about 19 mm, about 20 mm, about 21 mm, about 22 mm, about 23 mm, about 24 mm, about 25 mm, about 26 mm, about 27 mm, about 28 mm, about 29 mm, 30 mm, about 31 mm, about 32 mm, about 33 mm, about 34 mm, about 35 mm, about 36 mm, about 37 mm, about 38 mm, about 39 mm, or about 40 mm. In some embodiments, the dimension perpendicular to the greatest length (width, shown as "W" in the example in FIG. 1) is about 8 to about 20 mm or about 10 to about 20 mm, e.g., about 8 mm, about 9 mm, about 10 mm, about 11 mm, about 12 mm, about 13 mm, about 14 mm, about 15 mm, about 16 mm, about 17 mm, about 18 mm, about 19 mm, or about 20 mm. Certain non-limiting embodiments have the following largest approximate dimensions: about 38 mm (length) x about 18 mm (width); about 37.5 mm (length) x about 12 mm (width); about 38 mm (length) x about 12 mm (length); about 33 mm (length) x about 18 mm (width); about 33 mm (length) x about 12 mm (length), about 31 mm (length) x about 12 mm (width), about 30 mm (length) x about 12 mm (width), about 29 mm (length) x about 14 mm (width), about 28 mm (length) x about 13 mm (width), about 28 mm (length) x about 12 mm (width), about 27 mm (length) x about 16 mm (width), about 24 mm (length) x about 12 mm (width), and about 22 mm (length) x about 13 mm (width). The third dimension (thickness, T, not shown in FIG. 1) is believed to represent the three-dimensional thickness of the product, and this dimension may vary. In some embodiments, the thickness may vary, for example, but not limited to, from about 1 mm to about 20 mm or from about 2 mm to about 10 mm. Examples of certain thicknesses include, for example, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, about 10 mm, about 11 mm, about 12 mm, about 13 mm, about 14 mm, about 15 mm, about 16 mm, about 17 mm, about 18 mm, about 19 mm, or about 20 mm at the thickest point of the pouch.In some embodiments, the overall length, width, and thickness of the pouch product is about 130 mm or less, about 120 mm or less, about 110 mm or less, about 100 mm or less, about 90 mm or less, about 80 mm or less, about 70 mm or less, about 60 mm or less, about 50 mm or less, or about 40 mm or less, for example, about 30 mm to about 130 mm, about 30 mm to about 100 mm, about 50 to about 100 mm, or about 50 to about 70 mm. Advantageously, in such embodiments, the thickness of such pouch products is about 8 mm or less. The surface area (defined as length times width x 2) of one particular pouch is about 900 mm. 2 Below, approximately 800mm 2 Below, approximately 700mm 2 Below, approximately 600mm 2 Below, about 500mm 2 Below, approximately 400mm 2 Below, approximately 300mm 2 Below, approximately 250mm 2 Below, approximately 200mm 2 Less than or equal to 150 mm 2 or less (e.g., in some embodiments, about 100 mm 2 is the smallest.

[0285] In some embodiments, the disclosed pouches have a length L of about 35 to about 60 mm and a width W of about 8 to about 18 mm. Certain non-limiting examples of pouches provided herein are as follows: pouches having L≧35 mm and W≧8 mm, pouches having L≧35 mm and W≧10 mm, pouches having L≧35 mm and W≧12 mm, pouches having L≧35 mm and W≧14 mm, pouches having L≧35 mm and W≧16 mm, pouches having L≧40 mm and W≧8 mm, pouches having L≧40 mm and W≧10 mm. a pouch having L≧40mm and W≧12mm, a pouch having L≧40mm and W≧14mm, a pouch having L≧40mm and W≧16mm, a pouch having L≧50mm and W≧8mm, a pouch having L≧50mm and W≧10mm, a pouch having L≧50mm and W≧12mm, a pouch having L≧50mm and W≧14mm, and a pouch having L≧50mm and W≧16mm. In some embodiments, certain advantageous ranges of length and width for the large pouch are a length L of about 35 mm to about 60 mm, e.g., about 40 mm to about 60 mm, about 50 mm to about 60 mm, about 35 mm to about 50 mm, and about 35 mm to about 40 mm, and a width W of about 8 mm to about 16 mm, e.g., about 8 mm to about 14 mm, about 8 mm to about 12 mm, about 8 mm to about 10 mm, about 9 mm to about 16 mm, about 9 mm to about 14 mm, about 9 mm to about 12 mm, about 9 mm to about 10 mm, about 10 mm to about 16 mm, about 10 mm to about 14 mm, about 10 mm to about 12 mm, or about 14 to about 16. In various embodiments, all measurements of length, width, and thickness (i.e., all four sides of the pouch, plus thickness) are within the following ranges: In some embodiments, the overall length, width, and thickness of the large pouches provided herein are about 90 mm or more, about 100 mm or more, about 110 mm or more, about 120 mm or more, about 130 mm or more, about 140 mm or more, or about 150 mm or more. Advantageously, in such embodiments, the thickness of such pouches is about 2 mm or more (e.g., between about 2 and about 8 mm). The surface area (defined as length times width x 2) of certain pouches is about 300 mm. 2 Above, about 400mm 2 Above, about 500mm 2 Above, about 600mm2 or more, or about 700 mm 2 or more (for example, up to about 1000 mm 2 ), but the present disclosure is not limited thereto.

[0286] The pouch products described herein can be packaged in any suitable inner wrapper and / or outer container, see, for example, U.S. Patent No. 7,014,039 to Henson et al.; U.S. Patent No. 7,537,110 to Kutsch et al.; U.S. Patent No. 7,584,843 to Kutsch et al.; U.S. Patent No. 8,397,945 to Gelardi et al.; D592,956 to Thiellier; D594,154 to Patel et al.; and D625,178 to Bailey et al.; U.S. Patent Publication No. 2008 / 0173317 to Robinson et al.; U.S. Patent Publication No. 2009 / 0014343 to Clark et al.; U.S. Patent Publication No. 2009 / 0014450 to Bjorkholm; U.S. Patent Publication No. 2009 / 0014450 to Bella, which are incorporated herein by reference. See U.S. Patent Publication Nos. 2009 / 0250360 to Mah et al.; 2009 / 0266837 to Gelardi et al.; 2009 / 0223989 to Gelardi; 2009 / 0230003 to Thiellier; 2010 / 0084424 to Gelardi; and 2010 / 0133140 to Bailey et al.; 2010 / 0264157 to Bailey et al.; and 2011 / 0168712 to Bailey et al., which describe various types of containers for smokeless products.

[0287] The disclosed products constructed for oral use may be packaged and stored in any suitable packaging in much the same manner that conventional types of smokeless tobacco products are packaged and stored. For example, multiple packets or pouches may be contained in a cylindrical container. The shelf life of the product after preparation may vary. As used herein, "shelf life" refers to the period after preparation of the disclosed product. In some embodiments, one or more characteristics of the products disclosed herein (e.g., retention of whiteness, lack of discoloration, retention of volatile flavor components) are exhibited over some or all of the storage period. In some embodiments, the shelf life (i.e., preparation after period) is at least 1 day. In some embodiments, the shelf life is from about 1 day, about 2 days, or about 3 days, up to about 1 week, or from about 1 week to about 2 weeks, about 2 weeks to about 1 month, about 1 month to about 2 months, about 2 months to about 3 months, about 3 months to about 4 months, or about 4 months to about 5 months. In some embodiments, the shelf life is any number of days between about 1 day and about 150 days. In certain embodiments, the storage period may be greater than 5 months, e.g., at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, or at least about 12 months. EXAMPLES

[0288] Several compositions and corresponding nonwoven pouch products were produced according to the following examples.

[0289] Example 1: A first series of pouches was prepared with two nicotine components (along with corresponding comparative pouches having only one nicotine component, i.e., pouches without nicotine polymer complex). The composition of the mixture in each pouch is provided in Table 1 below (all values ​​are provided as weight percentages relative to the total weight of the mixture and include additional water sprayed during pouching, but exclude the weight of the outer pouch). The item designated as "Control" is a comparative sample that does not contain nicotine polacrilex, and the item designated as "Sample" contains both nicotine and nicotine polacrilex (as well as NaOH).

[0290] With the exception of the last item (water), the components were combined as follows: A mixture of MCC, NaCl, and nicotine polacrilex (if included) was combined with a liquid premix containing nicotine aqueous solution, flavoring, sodium bicarbonate, xylitol, sweetener (acesulfame-K or sucralose), and ammonium chloride (if included). For samples only, 5M sodium hydroxide was added to the mixture while mixing (this was not done for controls). The pH and moisture values ​​(provided via a hygrometer device) for this composition before pouching are provided in the table. Approximately 500-1000 mg of the mixture (e.g., depending on the pouch size) was placed into a non-woven fleece pouch. Additional water was then sprayed into the pouch (right-most item in the table) during or after pouching to a total moisture content of 48%-50%.

[0291] [Table 2] TIFF2024546045000006.tif111169

[0292] Example 2: A second series of pouches was prepared with two nicotine components. The composition of the mixture in each pouch is provided in Table 2 below (all values ​​are provided as weight percentages relative to the total weight of the mixture and include additional water sprayed during pouching, but exclude the weight of the outer pouch).

[0293] With the exception of the last item (water), the components were combined as follows: The MCC, NaCl, and nicotine polacrilex mixture was combined with a liquid premix containing nicotine aqueous solution, flavoring, sodium bicarbonate, xylitol, sweetener (acesulfame-K or sucralose), and ammonium chloride (if used). While mixing, 5M sodium hydroxide was added to the mixture. Approximately 400-600 mg of the mixture (e.g., depending on the size of the pouch) was placed into a non-woven fleece pouch. Additional water was then sprayed into the pouch during or after pouching to a total moisture content of 32% (last item in the table).

[0294] [Table 3]

[0295] Example 3: A third series of pouches was prepared with two nicotine components, and the composition of the mixture in each pouch is provided in Table 3 below (all values ​​are provided as weight percentages of the total weight of the mixture and include additional water sprayed during pouching, but exclude the weight of the outer pouch).

[0296] With the exception of the last item (water), the components were combined as follows: The MCC, NaCl, and nicotine polacrilex mixture was combined with a liquid premix containing nicotine aqueous solution, flavor, sodium bicarbonate, xylitol, sweetener (acesulfame-K or sucralose), and ammonium chloride (if used). While mixing, 5M sodium hydroxide was added to the mixture. Approximately 400-500 mg of the mixture was placed into a non-woven fleece pouch. Additional water was then sprayed into the pouch (last item in the table) during or after pouching to a total moisture content of approximately 45-50%.

[0297] [Table 4]

[0298] Example 4: A fourth series of pouches was prepared with two nicotine components. The composition of the mixture in each pouch is provided in Table 4 below (all values ​​are provided as weight percentages of the total weight of the mixture and include additional water sprayed during pouching, but exclude the weight of the outer pouch).

[0299] With the exception of the last item (water), the components were combined as follows: The mixture of MCC, NaCl, and nicotine polacrilex was combined with a liquid premix containing nicotine aqueous solution, flavoring, sodium bicarbonate, xylitol, acesulfame-K, and ammonium chloride (if used). While mixing, 6M sodium hydroxide was added to the mixture. Approximately 400-500 mg of the mixture was placed into a non-woven fleece pouch. Additional water was then sprayed into the pouch (last item in the table) during or after pouching to a total moisture content of approximately 45-50%.

[0300] [Table 5]

[0301] Example 5: Evaluation of nicotine release from nicotine polacrilex in the presence of sodium hydroxide or calcium hydroxide The use of sodium hydroxide and calcium hydroxide to pH adjustment reagents is compared. Aqueous solutions of nicotine polacrilex were evaluated for nicotine release at several pH values ​​in the presence of either sodium hydroxide or calcium hydroxide. Nicotine polacrilex (20% nicotine by weight) was added to 500 mL of water containing various amounts of either sodium hydroxide or calcium hydroxide and stirred for 10 minutes to obtain aqueous solutions calculated to theoretically contain 400 parts per million (ppm) of nicotine, calculated as the free base and as 100% release of theoretical nicotine from the resin. For each of the aforementioned solutions, 1 mL aliquots were analyzed for nicotine concentration as well as pH. The results are provided in Figure 2, which depicts the nicotine release from nicotine polacrilex in aqueous solution using sodium hydroxide and calcium hydroxide. Figure 2 shows that calcium hydroxide can effectively increase the pH of the solution and enhance the release of nicotine at lower pH values ​​compared to sodium hydroxide solutions at the same pH values. The data encompasses the resulting pH range from about 3.96 to about 7.92.

[0302] Example 6 : Evaluation of nicotine release from nicotine polacrilex in the presence of various salts and their combinations Aqueous solutions of various sodium and calcium salts in combination with nicotine polacrilex (20% nicotine by weight) were prepared by stirring the components for 10 minutes. 1 mL aliquots were taken and analyzed for nicotine concentration. The amount of each respective salt included in each solution was varied to obtain a range of calculated ionic strengths for each salt / nicotine polacrilex solution, ranging from about 1 to about 300 millimoles per liter. A chart of nicotine release versus ionic strength for such samples is provided in Figure 3.

[0303] Formulations containing nicotine polacrilex (20% nicotine by weight) alone and in the presence of various salts and combinations thereof were prepared using the ingredients and amounts provided in Table 5. Aqueous solutions were prepared by stirring the components for 10 minutes, then 1 mL aliquots were taken and analyzed for nicotine concentration.

[0304] [Table 6]

[0305] Nicotine polacrilex alone in aqueous solution (i.e., without any salt present, Powder A) was found to release only about 4.4% of the available nicotine, with the pH of the solution being about 7.75. In contrast, the addition of salt to the water during dissolution enhanced the release of nicotine from the polacrilex resin and also reduced the pH of the resulting solution. A chart of nicotine release versus ionic strength for each powder is provided as FIG. 4. Referring to FIG. 4, nicotine release increased as ionic strength increased. Overall, solutions containing calcium chloride or calcium lactate gluconate (Example Powders D and E) provided the greatest nicotine release, with the release of nicotine from nicotine polacrilex being greater than the release achievable by pH adjustment alone (shown by the area enclosed by the dotted line). For example, when combined with polacrilex with a multivalent cation salt, e.g., calcium lactate gluconate (1:1), a 60% greater release of nicotine was observed. The pH of the various solutions ranged from about 3.96 to about 7.92 (data not shown).

[0306] The amount of each respective salt included in each solution was varied to obtain a range of calculated ionic strengths for each salt / nicotine polacrilex solution, ranging from about 1 to about 300 millimoles per liter.

[0307] Example 6 Preparation and evaluation of nicotine polacrilex formulations and pouch products. Pouch products (Pouches AA, AB, AC, and AD) containing nicotine polacrilex and various salts were prepared using the ingredients and amounts provided in Tables 6, 7, 8, and 9, respectively. For each pouch, approximately 462 mg of the corresponding composition was used to fill a fleece pouch (viscose polyester blend fleece with acrylate binder) and the pouch was sprayed with water to obtain the desired moisture. The final pouch weight for each pouch was approximately 700 mg.

[0308] [Table 7]

[0309] [Table 8]

[0310] [Table 9]

[0311] [Table 10]

[0312] Nicotine release from pouch products containing nicotine polacrilex / salt-containing formulations provided in Tables 6-9 was evaluated as shown in FIG. 5 (no pH adjustment was used). Each of the pouches was cut open and complete artificial saliva ("CAS") (1 mL CAS per 300 mg sample) was added. Each solution was then placed on a heated rotary shaker set at 250 rpm for approximately 2 hours and the temperature was maintained at 37°C. An aliquot of each solution was removed and analyzed for nicotine concentration. The percent release of nicotine was calculated as the ratio of the analyzed nicotine to the theoretical nicotine present. LogD and pH were determined for pouches AA, AB, AC, and AD (see Table 10).

[0313] Pouch AD uses calcium lactate gluconate as a nicotine release enhancer and also contains sodium benzoate, which is believed to be capable of in situ formation of nicotine ion pair. Pouch AD shows a positive logD value. Pouch AC uses calcium glycerophosphate as a nicotine release enhancer to enhance the release of nicotine. However, the logP of Pouch AC is less favorable than Pouch AD. Without being bound by theory, it is believed that Pouch AC may have a lower logD than AD due to the lower water solubility of calcium glycerophosphate vs. calcium lactate gluconate (1:1) and / or the higher dosage of calcium glycerophosphate vs. calcium lactate gluconate (1:1), which may result in interference in nicotine ion pair formation.

[0314] [Table 11]

[0315] FIG. 5 also provides results for nicotine release versus pH of test solutions for certain powder compositions. Powders B and C from Table 5 were each added separately to 500 milliliters of deionized water in an amount sufficient to result in a solution calculated to theoretically contain 400 ppm nicotine (calculated as 100% release of free base and theoretical nicotine). Each solution was stirred for 10 minutes, and then a 1 milliliter aliquot of each solution was removed and analyzed for nicotine concentration. Each solution was pH adjusted to obtain a pH value in the range of about 7-12 using either 1 M NaOH (for a pH range of 7-9) or 5 M NaOH (pH value of about 11-12). The percent release of nicotine was calculated as the ratio of the analyzed nicotine to the theoretical amount of nicotine present.

[0316] It was observed that the pouched composition examples containing calcium salt (Pouches AC and AD) provided better nicotine release (about 70%) at acidic pH (e.g., about 6) compared to the compositions of Pouches AA and AB, and the powder compositions containing nicotine polacrilex and sodium chloride only (Powder B), or nicotine polacrilex, sodium chloride, and sodium benzoate (Powder C). It was found that the calcium salt effectively increased the pH of the solution, enhancing the release of nicotine at lower pH values ​​compared to a solution of sodium hydroxide at the same pH value. Notably, the nicotine release from the compositions of Powders B and C was only about 40% at around pH 6.

[0317] Example 7 Preparation of a pouch product containing nicotine and nicotine polacrilex Using the ingredients and amounts provided in Tables 11 and 12, pouch products containing nicotine polacrilex and nicotine with various salts are prepared. For each pouch, approximately 330 mg of the corresponding composition is used to fill a fleece pouch (viscose polyester blend fleece with acrylate binder) and the pouch is sprayed with water to obtain the desired moisture. The final pouch weight for each pouch is approximately 500 mg. The expected pH of the pouch compositions upon dissolution is in the range of about 5.5 to about 6.5, with an expected logD being positive.

[0318] [Table 12]

[0319] [Table 13]

[0320] Example 7 :Comparison of sodium hydroxide and calcium hydroxide Using the ingredients and amounts provided in Tables 13 and 14, pouch products containing nicotine polacrilex and nicotine are prepared with either sodium hydroxide or calcium hydroxide as a pH adjuster (Pouches BA and BB, respectively). For each pouch, approximately 330-340 mg of the corresponding composition is used to fill a fleece pouch (viscose polyester blend fleece with acrylate binder) and spray the pouch with water to a final weight of approximately 500 mg. Each pouch has dimensions of approximately 30×12 and contains 10 mg of nicotine per pouch. The expected pH of the pouch compositions ranges from about 8.5 to about 9.0.

[0321] [Table 14]

[0322] [Table 15]

[0323] Many variations and other embodiments of the invention to which this invention pertains will be devised by one skilled in the art having the benefit of the teachings presented in the foregoing description. It is to be understood, therefore, that the invention is not limited to the specific embodiments disclosed, and that variations and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

Claims

1. 1. A pouch product comprising an outer water-permeable pouch defining a cavity and a composition adapted for oral use located within the cavity, the composition having a total moisture content of about 5% or greater; A pouch product, wherein the composition comprises a nicotine component in the form of a nicotine polymer complex.

2. 10. The pouch product of claim 1, wherein the nicotine component is a first nicotine component and the composition further comprises a second nicotine component selected from the group consisting of nicotine and a nicotine salt.

3. 1. A pouch product comprising an outer water-permeable pouch defining a cavity and a composition adapted for oral use located within the cavity, the composition comprises a first nicotine component in the form of a nicotine polymer complex and a second nicotine component selected from the group consisting of nicotine and nicotine salts; Pouch products.

4. 2. The pouch product of claim 1, wherein the total moisture content is greater than or equal to about 15%, particularly greater than or equal to about 25%.

5. 10. The pouch product of claim 1, wherein the nicotine component is the only nicotine component contained within the composition.

6. 3. The pouch product of claim 2, wherein the first nicotine component is provided in an amount of about 2% to about 15% by weight and the second nicotine component is provided in an amount of about 0.5% to about 2% by weight, based on the total weight of the composition.

7. the nicotine provided by the first nicotine component is present in a higher weight percentage than the nicotine provided by the second nicotine component, or the nicotine provided by the first nicotine component is present in a lower weight percentage than the nicotine provided by the second nicotine component; The pouch product of claim 2.

8. A pouch product as described in claim 3, wherein the first nicotine component is provided in an amount of about 2% to about 15% by weight, and the second nicotine component is provided in an amount of about 0.5% to about 2% by weight, relative to the total weight of the composition.

9. The nicotine provided by the first nicotine component is present in a higher weight percentage than the nicotine provided by the second nicotine component, or the nicotine provided by the first nicotine component is present in a lower weight percentage than the nicotine provided by the second nicotine component. The pouch product of claim 3.

10. The nicotine polymer complex comprises a polymeric cation exchange resin, particularly the polymeric cation exchange resin comprises a polyacrylic polymer, particularly the nicotine polymer complex comprises nicotine polacrilex; The pouch product according to any one of claims 1 to 9.

11. The nicotine polymer complex is in the form of particles, in particular The particles are not coated, or the particles are coated with a coating comprising one or more loading ingredients and / or one or more pH adjusting agents; The pouch product according to any one of claims 1 to 9.

12. 10. The pouch product of any one of claims 1 to 9, wherein the nicotine polymer complex is in the form of particles having an average particle size of about 200 microns to about 400 microns.

13. 10. The pouch product of any of claims 1 to 9, wherein the nicotine polymer complex is in the form of particles exhibiting a bimodal particle size distribution, the bimodal particle size distribution comprising a first mode having a peak at about 75 to about 125 micrometers or about 80 to about 110 micrometers and a second mode having a peak at about 500 to about 1000 micrometers or about 700 to about 1000 micrometers.

14. 10. The pouch product of any one of claims 1 to 9, wherein the pouch product has a total moisture content of about 48% or less.

15. the second nicotine component is a tobacco-derived nicotine extract; or the second nicotine component is a synthetic nicotine, or the second nicotine component is a nicotine salt; The pouch product according to any one of claims 2 to 9.

16. 10. The pouch product of any one of claims 2 to 9, wherein at least a portion of the second nicotine component is in the form of a particulate non-tobacco material that has been processed to contain the second nicotine component and fibrous plant material that carries the second nicotine component.

17. The composition comprises one or more components selected from the group consisting of one or more additional fillers, binders, pH adjusters, colorants, disintegration aids, antioxidants, humectants, and preservatives, in particular the composition comprises a pH adjuster selected from sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, and combinations thereof; and / or The composition comprises about 5% or more of a humectant, in particular humectants include glycerol, The pouch product according to any one of claims 1 to 9.

18. 10. The pouch product of any one of claims 1 to 9, wherein the composition has a pH of about 6 to 9.

19. 10. The pouch product of any one of claims 1 to 9, wherein the composition comprises a calcium salt selected from the group consisting of calcium benzoate, calcium gluconate, calcium glycerol phosphate, calcium lactate, calcium lactate gluconate, and any combination thereof.

20. 1. A method for providing a pouch product having a modified nicotine release profile, comprising: an outer water-permeable pouch defining a cavity; and a composition adapted for oral use located within the cavity, the method comprising: incorporating nicotine in the form of a nicotine polymer complex; and A method comprising the step of incorporating water into and / or adding water to a pouch product to obtain a moist pouch product having a total moisture content of about 5% or greater.

21. 1. A method for providing a moist pouch product having a modified nicotine release profile, comprising: an outer water-permeable pouch defining a cavity; and a composition adapted for oral use located within the cavity, the method comprising: incorporating nicotine in the form of a nicotine polymer complex; and A method comprising the step of incorporating water within and / or adding water to a pouch product to obtain a moist pouch product having a total moisture content of about 25% or greater.

22. 1. A method for providing a pouch product having a modified nicotine release profile, comprising: an outer water-permeable pouch defining a cavity; and a composition adapted for oral use located within the cavity, the method comprising: incorporating nicotine in the form of two or more different nicotine components, including a first nicotine component in the form of a nicotine polymer complex; and a second nicotine component selected from the group consisting of nicotine and a nicotine salt; and A method comprising the step of incorporating water into and / or adding water to a pouch product to obtain a moist pouch product having a total moisture content of about 5% or greater.

23. 1. A method for providing a moist pouch product having a modified nicotine release profile, comprising: an outer water-permeable pouch defining a cavity; and a composition adapted for oral use located within the cavity, the method comprising: incorporating nicotine in the form of two or more different nicotine components, including a first nicotine component in the form of a nicotine polymer complex; and a second nicotine component selected from the group consisting of nicotine and a nicotine salt; and A method comprising the step of incorporating water within and / or adding water to a pouch product to obtain a moist pouch product having a total moisture content of about 25% or greater.

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