Oral Products Containing Basic Amine and Ion Pairing Agents - Patent application

Abstract

The present disclosure provides a composition adapted for oral use, comprising at least one filler, water, a basic amine, and an organic acid, an alkali metal salt of an organic acid, or a combination thereof, wherein the organic acid has a logP value of about 1 to about 12. At least a portion of the basic amine is associated with at least a portion of the organic acid or its alkali metal salt. The association is in the form of a basic amine-organic acid salt, an ion pair between the basic amine and the conjugate base of the organic acid, or a combination of both. The organic acid is a monoester of a dicarboxylic acid, or a carotenoid derivative having one or more carboxylic acids.

Description

[Technical field]

[0001] The present disclosure relates to compositions intended for human use. The compositions are adapted for oral use and deliver substances such as nicotine, flavorings and / or active ingredients during use. Such compositions may include tobacco or tobacco-derived products or may be tobacco-free substitutes. [Background technology]

[0002] Tobacco may be enjoyed in so-called "smokeless" forms. Particularly popular smokeless tobacco products are used by inserting some form of processed tobacco or tobacco-containing formulation into the user's oral cavity. Traditional formats for such smokeless tobacco products include moist snuff, snus and chewing tobacco, which are usually formed almost entirely from particulate, granular or cut tobacco and are either portioned by the user or provided to the user in single portions, such as in disposable pouches or sachets. Other traditional forms of smokeless products include compressed or agglomerated forms, such as plugs, tablets or pellets. Alternative product formats, such as tobacco-containing gums and mixtures of tobacco with other plant materials, are also known.See, for example, U.S. Pat. Nos. 1,376,586 to Schwartz; 4,513,756 to Pittman et al.; 4,528,993 to Sensabaugh, Jr. et al.; 4,624,269 to Story et al.; 4,991,599 to Tibbetts; 4,987,907 to Townsend; and 4,987,907 to Sprinkl, each of which is incorporated herein by reference. No. 5,092,352 to Le, III et al.; No. 5,387,416 to White et al.; No. 6,668,839 to Williams; No. 6,834,654 to Williams; No. 6,953,040 to Atchley et al.; No. 7,032,601 to Atchley et al.; and No. 7,694,686 to Atchley et al.; U.S. Patent Publication No. 2004 / 002 to Williams. No. 2005 / 0115580 to Quinter et al.; No. 2006 / 0191548 to Strickland et al.; No. 2007 / 0062549 to Holton, Jr. et al.; No. 2007 / 0186941 to Holton, Jr. et al.; No. 2007 / 0186942 to Strickland et al.; No. 2008 / 0029110 to Dube et al.; No. 2008 / 0029110 to Robinson et al. See WO 2008 / 0029116; Robinson et al., WO 2008 / 0173317; Neilsen et al., WO 2008 / 0209586; Essen et al., WO 2009 / 0065013; and Atchley, WO 2010 / 0282267, as well as WO 2004 / 095959 to Arnarp et al., for types, ingredients, and processing methods of smokeless tobacco formulations.

[0003] The construction of smokeless tobacco products that combine tobacco materials, nicotine components and / or other active ingredients with various binders and fillers has been proposed more recently, with exemplary product formats including lozenges, pastilles, gels, extruded forms, 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. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] U.S. Pat. No. 1,376,586 [Patent Document 2] U.S. Pat. No. 4,513,756 [Patent Document 3] U.S. Pat. No. 4,528,993 [Patent Document 4] U.S. Pat. No. 4,624,269 [Patent Document 5] U.S. Pat. No. 4,991,599 [Patent Document 6] U.S. Pat. No. 4,987,907 [Patent Document 7] U.S. Patent No. 5,092,352 [Patent Document 8] U.S. Pat. No. 5,387,416 [Patent Document 9] U.S. Patent No. 6,668,839 [Patent Document 10] U.S. Patent No. 6,834,654 [Patent Document 11] U.S. Patent No. 6,953,040 [Patent Document 12] U.S. Patent No. 7,032,601 [Patent Document 13] U.S. Pat. No. 7,694,686 [Patent Document 14] US Patent Application Publication No. 2004 / 0020503 [Patent Document 15] US Patent Application Publication No. 2005 / 0115580 [Patent Document 16] US Patent Application Publication No. 2006 / 0191548 [Patent Document 17] US Patent Application Publication No. 2007 / 0062549 [Patent Document 18] US Patent Application Publication No. 2007 / 0186941 [Patent Document 19] US Patent Application Publication No. 2007 / 0186942 [Patent Document 20] US Patent Application Publication No. 2008 / 0029110 [Patent Document 21] US Patent Application Publication No. 2008 / 0029116 [Patent Document 22] US Patent Application Publication No. 2008 / 0173317 [Patent Document 23] US Patent Application Publication No. 2008 / 0209586 [Patent Document 24] US Patent Application Publication No. 2009 / 0065013 [Patent Document 25] US Patent Application Publication No. 2010 / 0282267 [Patent Document 26] International Publication No. 2004 / 095959 [Patent Document 27] US Patent Application Publication No. 2008 / 0196730 [Patent Document 28] US Patent Application Publication No. 2008 / 0305216 [Patent Document 29] US Patent Application Publication No. 2009 / 0293889 [Patent Document 30] US Patent Application Publication No. 2010 / 0291245 [Patent Document 31] US Patent Application Publication No. 2011 / 0139164 [Patent Document 32] US Patent Application Publication No. 2012 / 0037175 [Patent Document 33] US Patent Application Publication No. 2012 / 0055494 [Patent Document 34] US Patent Application Publication No. 2012 / 0138073 [Patent Document 35] US Patent Application Publication No. 2012 / 0138074 [Patent Document 36] US Patent Application Publication No. 2013 / 0074855 [Patent Document 37] US Patent Application Publication No. 2013 / 0074856 [Patent Document 38] US Patent Application Publication No. 2013 / 0152953 [Patent Document 39] US Patent Application Publication No. 2013 / 0274296 [Patent Document 40] US Patent Application Publication No. 2015 / 0068545 [Patent Document 41] US Patent Application Publication No. 2015 / 0101627 [Patent Document 42] US Patent Application Publication No. 2015 / 0230515 Summary of the Invention [Means for solving the problem]

[0005] Oral products are used by placing a nicotine-containing matrix between the cheek and gum. Nicotine is then released from the product and is typically absorbed through the oral mucosa, thereby entering the bloodstream where it is circulated systemically. Flavor stability and positive sensory attributes are important factors for an oral product to be accepted by the user. The organoleptic effects of flavors have been shown to be particularly sensitive to the pH of the product. When the pH of the product exceeds about 7.0, the appearance, aroma and taste effects of some flavors deteriorate over time and nicotine may evaporate from the product. In particular, such instability is evident in the case of certain flavors, such as ethyl vanillin, lime and cinnamon, which also cause the originally white product to darken over time. However, lowering the pH increases the degree to which nicotine is present in a protonated form. As a dibasic alkaloid, nicotine is capable of accepting two protons (pyridine ring nitrogen: log K a1 = 3.41; and pyrrolidine ring nitrogen: log K a2 =8.02), significantly changing the polarity. The overall polarity of nicotine increases from log(P)=1.09 (unprotonated nicotine) to -2.07 (for nicotine protonated at the pyrrolidine ring nitrogen). Passive diffusion of substances such as nicotine through membranes (e.g., mucous membranes) is a function of the polarity and membrane properties of the molecule, as well as molecular size and ionization (Kokate et al., PharmSciTech 2008, 9, 501-504).

[0006] Without wishing to be bound by theory, the downward shift in logP as a result of the protonation state is believed to be the primary driving force behind the decline in nicotine absorption with decreasing pH (Nair et al., Journal of Pharmaceutical Sciences 1997, 86, 257-262; Chen et al., International Journal of Pharmaceutics 1999, 184, 63-72; Adrian et al., International Journal of Pharmaceutics 2006, 311, 196-202). Specifically, as reported in Adrian et al., for a nicotine solution at pH=6 (where nicotine is primarily monoprotonated), there is still some diffusion through human oral tissues in perfused cells, but the rate is significantly reduced (by a factor of about seven) compared to a nicotine solution at pH 8.1.

[0007] The present disclosure generally provides compositions configured for oral use, comprising a basic amine and an organic acid, an alkali metal salt of an organic acid, or a combination thereof, wherein the organic acid has a logP value of about 1 to about 12, such as about 3 to about 10, or about 3 to about 8. At least a portion of the basic amine is associated with at least a portion of the organic acid or its alkali metal salt, and the association is in the form of a basic amine-organic acid salt, in the form of an ion pair between the basic amine and the conjugate base of the organic acid, or in the form of both. According to the present disclosure, it has been found that certain carotenoid derivatives having one or more carboxylic acids and certain dicarboxylic acid monoesters may have the opportunity to form suitable ion pairs with basic amines, such as nicotine, to further impart desirable characteristics, such as color, cooling sensation, reduced pharyngeal irritation, or a combination thereof, to compositions containing them.

[0008] Thus, in one aspect, there is provided a composition adapted for use in the oral cavity comprising at least one filler; a basic amine; water; and an organic acid, an alkali metal salt of an organic acid, or a combination thereof, wherein the organic acid has a logP value of from about 1 to about 12, at least a portion of the basic amine is in association with at least a portion of the organic acid or its alkali metal salt, the association being in the form of a basic amine-organic acid salt, an ion pair between the basic amine and a conjugate base of the organic acid, or both, and the organic acid is a monoester of a dicarboxylic acid or a carotenoid derivative having one or more carboxylic acids.

[0009] In some embodiments, the organic acid has a log P value of about 3 to about 12. In some embodiments, the organic acid has a log P value of about 3 to about 10. In some embodiments, the organic acid has a log P value of about 3 to about 8.

[0010] In some embodiments, the organic acid is a menthyl monoester or a tocopherol monoester of a dicarboxylic 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 organic acid is tocopherol succinate, monomenthyl succinate, monomenthyl fumarate, monomenthyl glutarate, or a combination thereof.

[0011] 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-nonenoic acid (bixin), or an isomer thereof. 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).

[0012] In some embodiments, the composition further comprises a solubility improver, which is glycerol or propylene glycol, or another humectant as described herein.

[0013] In some embodiments, the compositions include 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, an alkali metal salt thereof, or a combination thereof, relative to the basic amine, calculated as the amine free base. In some embodiments, the compositions include from about 2 to about 10 molar equivalents of an organic acid, an alkali metal salt thereof, or a combination thereof, relative to the basic amine, calculated as the amine free base.

[0014] In some embodiments, the organic acid further comprises benzoic acid, an alkali metal salt thereof, or a combination thereof.

[0015] In some embodiments, the alkali metal is sodium or potassium.

[0016] In some embodiments, the composition comprises an organic acid and a sodium salt of the organic acid, hi some embodiments, the ratio of the organic acid to the sodium salt of the organic acid is from about 0.1 to about 10.

[0017] In some embodiments, the pH of the composition is about 4.0 to about 9.0. In some embodiments, the pH of the composition is about 4.5 to about 7. In some embodiments, the pH of the composition is about 5.5 to about 7. In some embodiments, the pH of the composition is about 4.0 to about 5.5. In some embodiments, the pH of the composition is about 7.0 to about 9.0.

[0018] In some embodiments, the basic amine is nicotine, hi some embodiments, nicotine is present in an amount of about 0.001 to about 10% by weight of the composition, calculated as the free base, based on the total weight of the composition.

[0019] In some embodiments, the at least one filler is a cellulose material. In some embodiments, the cellulose material comprises microcrystalline cellulose. In some embodiments, the at least one filler further comprises a cellulose derivative in an amount of about 1 to about 3% by weight based on the total weight of the composition. In some embodiments, the cellulose derivative is hydroxypropyl cellulose.

[0020] In some embodiments, the composition comprises, based on the total weight of the composition, from about 10 to about 50% of at least one filler; and from about 5 to about 60% by weight of water.

[0021] In some embodiments, the composition further comprises one or more active ingredients, one or more flavoring agents, one or more salts, one or more sweetening agents, one or more binders, one or more humectants, one or more gums, tobacco materials, or combinations thereof.

[0022] In some embodiments, the composition further comprises one or more active ingredients selected from the group consisting of nutraceuticals, botanicals, stimulants, amino acids, vitamins, and cannabinoids.

[0023] In some embodiments, the composition comprises about 10% or less by weight of tobacco material, excluding any nicotine components present, based on the total weight of the composition. In some embodiments, the composition does not comprise tobacco material.

[0024] In some embodiments, the composition is enclosed within a pouch to form a pouched product, optionally in granular form.

[0025] In some embodiments, the composition is in the form of a gel, pastille, gum, chew, melt, tablet, lozenge, granule, or powder.

[0026] The present disclosure includes, but is not limited to, the following embodiments.

[0027] Embodiment 1: A composition configured for use in the oral cavity comprising at least one filler; a basic amine; water; and an organic acid, an alkali metal salt of an organic acid, or a combination thereof, wherein the organic acid has a logP value of about 1 to about 12, at least a portion of the basic amine is associated with at least a portion of the organic acid or its alkali metal salt, and the bond is in the form of a basic amine-organic acid salt, an ion pair between the basic amine and a conjugate base of the organic acid, or both, and the organic acid is a monoester of a dicarboxylic acid or a carotenoid derivative having one or more carboxylic acids.

[0028] Embodiment 2: The composition of embodiment 1, wherein the organic acid has a logP value of from about 3 to about 10, or from about 3 to about 8.

[0029] Embodiment 3: The composition of embodiment 1 or 2, wherein the organic acid is a menthyl monoester or a tocopherol monoester of a dicarboxylic acid.

[0030] Embodiment 4: The composition of embodiment 3, wherein the dicarboxylic acid is malonic acid, succinic acid, glutaric acid, adipic acid, fumaric acid, maleic acid, or a combination thereof.

[0031] Embodiment 5: The composition of any one of embodiments 1-3, wherein the organic acid is norbixin, bixin, or an isomer thereof.

[0032] Embodiment 6: The composition of any one of embodiments 1-3, wherein the organic acid is tocopherol succinate, monomenthyl succinate, monomenthyl fumarate, monomenthyl glutarate, or a combination thereof.

[0033] Embodiment 7: The composition of any one of embodiments 1-6, further comprising a solubility improver.

[0034] Embodiment 8: The composition of embodiment 7, wherein the solubility improver is glycerol or propylene glycol.

[0035] Embodiment 9: The composition of any one of embodiments 1-8, comprising 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, an alkali metal salt thereof, or a combination thereof, relative to the basic amine, calculated as the amine free base.

[0036] Embodiment 10: The composition of any one of embodiments 1 to 9, comprising about 2 to about 10 molar equivalents of an organic acid, an alkali metal salt thereof, or a combination thereof, relative to the basic amine, calculated as the amine free base.

[0037] Embodiment 11: The composition of any one of embodiments 1-11, wherein the organic acid further comprises benzoic acid, an alkali metal salt thereof, or a combination thereof.

[0038] Embodiment 12: The composition of any one of embodiments 1 to 11, wherein the alkali metal is sodium or potassium.

[0039] Embodiment 13: The composition of any one of embodiments 1-12, comprising an organic acid and a sodium salt of the organic acid.

[0040] Embodiment 14: The composition of any one of embodiments 1-13, wherein the ratio of organic acid to the sodium salt of the organic acid is from about 0.1 to about 10.

[0041] Embodiment 15: The composition of any one of embodiments 1 to 14, wherein the pH of the composition is from about 4.0 to about 9.0.

[0042] Embodiment 16: The composition of any one of embodiments 1 to 15, wherein the pH of the composition is from about 4.5 to about 7.

[0043] Embodiment 17: The composition of any one of embodiments 1 to 16, wherein the pH of the composition is from about 5.5 to about 7.

[0044] Embodiment 18: The composition of any one of embodiments 1 to 15, wherein the pH of the composition is from about 4.0 to about 5.5.

[0045] Embodiment 19: The composition of any one of embodiments 1 to 14, wherein the pH of the composition is from about 7.0 to about 9.0.

[0046] Embodiment 20: The composition of any one of embodiments 1-19, wherein the basic amine is nicotine.

[0047] Embodiment 21: The composition of embodiment 20, wherein the nicotine is present in an amount of about 0.001 to about 10% by weight of the composition, calculated as the free base, based on the total weight of the composition.

[0048] Embodiment 22: The composition of any one of embodiments 1 to 21, wherein at least one filler comprises a cellulosic material.

[0049] Embodiment 23: The composition of any one of embodiments 1 to 22, wherein the cellulose material comprises microcrystalline cellulose.

[0050] Embodiment 24: The composition of any one of embodiments 1 to 23, wherein the at least one filler further comprises a cellulose derivative in an amount of about 1% to about 3% by weight, based on the total weight of the composition.

[0051] Embodiment 25: The composition of embodiment 24, wherein the cellulose derivative is hydroxypropyl cellulose.

[0052] Embodiment 26: The composition of any one of embodiments 1 to 25, comprising from about 10 to about 50% of at least one filler; and from about 5 to about 60% by weight of water, based on the total weight of the composition.

[0053] Embodiment 27: The composition of any one of embodiments 1 to 26, further comprising one or more active ingredients, one or more flavoring agents, one or more salts, one or more sweetening agents, one or more binders, one or more humectants, one or more gums, tobacco materials, or combinations thereof.

[0054] Embodiment 28: The composition of any one of embodiments 1 to 27, further comprising one or more active ingredients selected from the group consisting of functional foods, botanicals, stimulants, amino acids, vitamins and cannabinoids.

[0055] Embodiment 29: The composition of any one of embodiments 1 to 28, comprising about 10% by weight or less of tobacco material, excluding any nicotine components present, based on the total weight of the composition.

[0056] Embodiment 30: The composition of any one of embodiments 1 to 28, which does not comprise tobacco material.

[0057] Embodiment 31: The composition of any one of embodiments 1 to 30, wherein the composition is optionally in granular form and enclosed within a pouch to form a pouched product.

[0058] Embodiment 32: The composition of any one of embodiments 1 to 30, in the form of a gel, pastille, gum, chew, melt, tablet, lozenge, granular material, or powder.

[0059] Embodiment 33: A composition adapted for the oral cavity comprising at least one filler; a basic amine (e.g., nicotine); water; and an organic acid, wherein the organic acid is a monoester of a dicarboxylic acid, such as a menthyl monoester or a tocopherol monoester of a dicarboxylic acid, or a carotenoid derivative having one or more carboxylic acids, exemplary dicarboxylic acids include malonic acid, succinic acid, glutaric acid, adipic acid, fumaric acid, maleic acid, or combinations thereof, or the organic acid is norbixin, bixin, or an isomer thereof, or the organic acid is tocopherol succinate, monomenthyl succinate, monomenthyl fumarate, monomenthyl glutarate, or combinations thereof.

[0060] These and other features, aspects and advantages of the present disclosure will become apparent from 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.

[0061] Having thus described aspects of the disclosure in the foregoing general terms, reference is now made to the accompanying drawings, which are not necessarily drawn to scale, and which are merely examples and should not be construed as limiting the disclosure. [Brief description of the drawings]

[0062] [Figure 1] FIG. 1 is a perspective view of an embodiment of a pouched product according to an exemplary embodiment of the present disclosure, comprising a pouch or fleece at least partially filled with a composition configured for the oral cavity. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0063] The present disclosure will now be described more fully hereinafter with reference to exemplary embodiments thereof. These exemplary embodiments are described so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art. Indeed, the present disclosure may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements.

[0064] As used in this specification and the claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0065] References to "dry weight percent" or "dry weight basis" refer to weight based on dry ingredients (i.e., all ingredients excluding water). References to "wet weight" refer to the weight of the mixture including water. Unless otherwise indicated, references to a "weight percent" of a mixture reflect the total wet weight of the mixture (i.e., including water).

[0066] To satisfy customers, it is desirable to provide a basic amine-containing composition configured for oral use that retains the initial content of basic amine during storage and delivers substantially the entire amount of basic amine initially present in the composition.The present disclosure provides compositions that combine a basic amine with a non-polar or lipophilic organic acid salt in the form of a basic amine-organic acid salt, an ion pair between the basic amine and the conjugate base of the organic acid, or both.

[0067] In some embodiments, the basic amine is nicotine. In certain embodiments, the presence of non-polar organic acid or lipophilic organic acid can increase the membrane permeability of nicotine when it forms an ionic form with nicotine, compared to compositions that contain polar organic acid and are designed for oral use. Selecting certain organic acids, such as carotenoid derivatives with one or more carboxylic acids or certain monoesters of dicarboxylic acids, can provide the composition with more desirable sensory properties, such as color or cooling sensation, respectively.

[0068] composition The compositions disclosed herein include at least one filler, a basic amine such as nicotine or a nicotine component, water and an organic acid, an alkali metal salt of an organic acid, or a combination thereof, where the organic acid has a logP value of about 3 to about 12. At least a portion of the basic amine is associated with at least a portion of the organic acid or its alkali metal salt. The association is in the form of a basic amine-organic acid salt, an ion pair between the basic amine and the conjugate base of the organic acid, or both. The relative amounts of the various components within the composition may vary and are typically selected to provide the composition with the desired sensory and performance characteristics. Exemplary individual components of the composition are described further herein below.

[0069] Ion pairing As disclosed herein, at least a portion of basic amine is associated with at least a portion of organic acid or its alkali metal salt.Depending on multiple variables (concentration, pH, nature of organic acid, etc.), the basic amine present in the composition can exist in multiple forms, including ion pairing, in solution (i.e., fully solvated), as free base, as cation, as salt, or any combination thereof.In some embodiments, the association between basic amine and at least a portion of organic acid or its alkali metal salt is in the form of ion pairing between basic amine and conjugate base of organic acid.

[0070] Ion pairing describes the partial association of oppositely charged ions in a relatively concentrated solution to form distinct chemical species called ion pairs. The strength of the association (i.e., ion pairing) depends on the electrostatic force of attraction between a cation and anion (i.e., a protonated basic amine, such as nicotine, and a conjugate base of an 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 oral use of the compositions (e.g., upon contact with saliva), the basic amines, such as nicotine and the conjugate bases of organic acids, 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 may minimize chemical decomposition of the basic amine and / or may increase the oral availability of the basic amine (e.g., nicotine). At alkaline pH values ​​(e.g., about 7.5 to about 9, etc.), certain basic amines, such as nicotine, exist mostly in a free base form, which has relatively low aqueous solubility and low stability against solvent evaporation and oxidative degradation, but high mucosal availability. Conversely, at acidic pH values ​​(e.g., about 6.5 to about 4, etc.), certain basic amines, such as nicotine, exist mostly in a protonated form, which has relatively high aqueous solubility and higher stability against solvent evaporation and oxidative degradation, but low mucosal availability. Surprisingly, according to the present disclosure, it has been found that the stability, solubility and availability properties of nicotine in compositions configured for the oral cavity can be mutually enhanced by ion pairing or salt formation of nicotine with a suitable organic acid and / or its conjugate base. Specifically, ion pairs of moderately lipid-soluble nicotine-organic acids provide advantageous stability and absorption properties. Lipid solubility is conveniently measured in terms of logP, the partition coefficient of a molecule between lipophilic and aqueous phases, usually octanol and water, respectively.Octanol-water partitioning, which favors distribution of the basic amine-organic acid ion pair into octanol, predicts good absorption across the oral mucosa of the basic amines present in the composition.

[0071] Those skilled in the art will recognize that the degree of ion pairing in the disclosed compositions, both before and during use by the user, may vary based on, for example, pH, the nature of the organic acid present in the composition, the concentration of the basic amine, the concentration of the organic acid or the conjugate base of the organic acid, the water content of the composition, the ionic strength of the composition, etc. 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 may be demonstrated by proxy measures such as the partitioning of the basic amine between octanol and water, or by conducting membrane permeability studies of aqueous solutions of the basic amine and the organic acid and / or its conjugate base.

[0072] 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 (-COH) or sulfonic acids (-SOOH). As used herein, reference to an organic acid refers to an organic acid that has been intentionally added. In this context, an organic acid may 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 an organic acid that may be naturally present in a composition component, e.g., a tobacco material).

[0073] Suitable organic acids typically have a range of lipophilicity (i.e., polarity that provides an appropriate balance between water and organic solubility). Typically, the lipophilicity of suitable organic acids, as expressed in 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.

[0074] 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 that result in favorable octanol-water partitioning of the ion pair, and thus are polar enough to partition nicotine into octanol rather than water. As discussed above, such partitioning into octanol predicts favorable oral availability.

[0075] In certain embodiments, the organic acid has a logP 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., including glycerin or propylene glycol in the composition) may favor the dissolution of the organic acid and the corresponding salt or its ion pair with a basic amine in the case of highly lipophilic organic acids (e.g., greater than about 4.5).

[0076] 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.

[0077] 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. 2 It 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.

[0078] "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 monocyclic rings or rings having 7 to 12 carbon atoms as bicyclic rings. 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).

[0079] 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.

[0080] "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 (e.g., 2-6 carbon atoms and 1-3 heteroatoms selected from N, O, and S) having 3-7 ring members or bicyclic (e.g., 4-9 carbon atoms and 1-3 heteroatoms selected from N, O, and S) having 7-10 ring members, 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.

[0081] "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.

[0082] 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.

[0083] In some embodiments, the organic acid is an alkylsulfonic acid. Non-limiting examples of alkylsulfonic acids include propanesulfonic acid, heptanesulfonic acid, and octane sulfonic acid.

[0084] 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.

[0085] In some embodiments, the organic acid can contain 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., 2-4 carboxylic acid groups), one or more of the carboxylic acid groups may be esterified. Non-limiting examples include succinic acid monoethyl ester, monomethyl fumarate, monomethyl citrate, or dimethyl citrate.

[0086] 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.

[0087] In some embodiments, the organic acid is an aryl carboxylic acid or 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.

[0088] Further non-limiting examples of organic acids that may be useful in certain embodiments include 2-(4-isobutylphenyl)propanoic acid, 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, schizoic acid (+), camphor-10-sulfonic acid (+), cinnamic acid, cyclamic acid, dodecyl sulfuric acid, ethane-1,2-disulfonic ... These include sulfonic, furoic, mucous, gentisic, glucoheptonic, gluconic, glucuronic, glutamic, glycerophosphoric, glycolic, hippuric, isobutyric, isovaleric, lactobionic, lauric, levulinic, malic, malonic, mandelic, methanesulfonic, naphthalene-1,5-disulfonic, naphthalene-2-sulfonic, oleic, palmitic, pamoic, phenylacetic, pyroglutamic, pyruvic, sebacic, stearic, and undecylenic acids.

[0089] Examples of suitable acids include, but are not limited to, the list of organic acids in Table 1.

[0090] [Table 1]

[0091] The selection of an organic acid may further depend on additional properties in addition to considering the logP value. For example, the organic acid should be one that is recognized as safe for human consumption, have acceptable flavor, odor, volatility, stability, etc. Determination of appropriate organic acids is within the skill of the art.

[0092] 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.

[0093] 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.

[0094] 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:

[0095] [ka]

[0096] 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:

[0097] [ka]

[0098] 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. As such, it is also 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, for example, but not limited to, desirable organoleptic properties, stability, as flavor ingredients in compositions that have logP values ​​outside of the desired range for a purpose. Furthermore, 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 the desired ion pairing while keeping the concentration of any single organic acid in the composition below the threshold that has been found to be objectionable from a sensory standpoint.

[0099] In some embodiments, the composition comprises an organic acid that is a monoester of a dicarboxylic acid or a carotenoid derivative having one or more carboxylic acids as described hereinabove, and further comprises an additional organic acid or a salt thereof, hi some embodiments, the additional organic acid is benzoic acid, an alkali metal salt thereof, or a combination thereof.

[0100] In some embodiments, the composition comprises an alkali 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. Suitable alkali metal salts 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 the organic acid.

[0101] In some embodiments, the weight ratio of organic acid to sodium salt (or other alkali metal) is from about 0.1 to about 10, such as 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 sodium salt are added to the other components of the composition, and the organic acid is added in an amount in excess of the sodium salt, in an equimolar amount to the sodium salt, or as a part of the sodium salt. Those skilled in the art will appreciate that the relative amounts will be 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 a desired pH level of the composition, while the alkali metal (e.g., sodium) salt is added in an amount that results in a desired range of ion pairing. Those skilled in the art will appreciate that the amount of organic acid (i.e., protonated form) present in the composition relative to the alkali metal salt or conjugate base form present in the composition will vary with the pH of the composition and the pKa of the organic acid, as well as the actual relative amounts initially added to the composition.

[0102] The amount of organic acid or its alkali metal salt present in the composition relative to the basic amine (e.g., nicotine) may vary. In general, as the concentration of the organic acid (or its conjugate base) increases, the proportion of the basic amine (e.g., nicotine) that forms an ion pair with the organic acid increases. This results in a higher logP (log of the partition coefficient). 10In 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, an alkali metal salt thereof, or a combination thereof, relative to the basic amine (e.g., nicotine), calculated as the free base of the basic amine.

[0103] In some embodiments, the compositions include about 2 to about 10, or about 2 to about 5 molar equivalents of an organic acid, an alkali metal salt thereof, or a combination thereof, to a basic amine (e.g., nicotine) on a free base basis. In some embodiments, the organic acid, an alkali metal salt thereof, or a combination thereof is present in a molar ratio with the basic amine (e.g., nicotine) that is from about 2, about 3, about 4, or about 5, to about 6, about 7, about 8, about 9, or about 10. In embodiments in which more than one organic acid, an alkali metal salt thereof, or both are present, it should be understood that such molar ratio reflects the total amount of organic acid present.

[0104] In certain embodiments, the inclusion of the organic acid is sufficient to provide a composition pH of about 4.0 to about 9.0, such as about 4.5 to about 7.0 or about 5.5 to about 7.0, about 4.0 to about 5.5 or about 7.0 to about 9.0. In some embodiments, the inclusion of the organic acid is sufficient to provide a composition pH 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 composition pH 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.

[0105] In some embodiments, the organic acid is added to the other components of the composition as a free acid, either neat (i.e., in its original solid or liquid form), or as a solution, for example, in water. In some embodiments, the alkali metal salt of the organic acid is added to the other components of the composition, either neat or as a solution, for example, in water. In some embodiments, the organic acid and the basic amine (e.g., nicotine) are combined to form a salt, either before addition to the composition or before the salt is formed therein, and remain in the composition. In other embodiments, the organic acid and the basic amine (e.g., nicotine) are present as individual components in the composition, and form an ion pair upon contact with moisture (e.g., saliva in the user's mouth).

[0106] In some embodiments, the organic acid is added to 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 alkali metal salt of the organic acid is added to 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 (e.g., nicotine) are combined to form a salt, either before addition to the composition or before the salt is formed, and remain in the composition as such. In other embodiments, the organic acid and the basic amine (e.g., nicotine) are present in the composition as individual components, and form an ion pair when contacted with moisture (e.g., saliva in the user's mouth).

[0107] In some embodiments, the oral composition comprises nicotine benzoate and sodium benzoate, and at least a portion of the nicotine and benzoate ions present are in ion-paired form. In some embodiments, the composition comprises nicotine benzoate, sodium benzoate, and an organic acid, an alkali metal salt of an organic acid, or a combination thereof, wherein the organic acid has a logP value of about 1 to about 12, and the organic acid is a monoester of a dicarboxylic acid or a carotenoid derivative having one or more carboxylic acids.

[0108] In some embodiments, the oral composition further comprises a solubility improver to increase the solubility of at least one of the organic acids or salts thereof. Suitable solubility improvers include, but are not limited to, humectants as described herein, such as glycerol or propylene glycol.

[0109] Basic amines The compositions disclosed herein include basic amines. "Basic amine" refers to a molecule that includes at least one basic amine functional group. Examples of basic amines include, but are not limited to, alkaloids. "Basic amine functional group" refers to a group that contains a nitrogen atom that has a lone pair of electrons. The basic amine functional group is attached to or incorporated within a molecule via one or more covalent bonds to said nitrogen atom. Basic amines may be primary, secondary, or tertiary amines, meaning that the nitrogen has one, two, or three covalent bonds to a carbon atom. Due to the lone pair of electrons on the nitrogen atom, such amines are referred to as "basic", meaning that the lone pair is available for hydrogen bonding. The basicity of basic amines (i.e., the electron density on the nitrogen atom, and therefore the availability and strength of hydrogen bonding to the nitrogen atom) can be affected by the nature of the neighboring atoms, the steric bulk of the molecule, and the like.

[0110] Generally, the basic amine is released from the composition and absorbed through the oral mucosa, thereby entering the bloodstream, where it is circulated systemically. Generally, the basic amine is present in the composition or present as an active ingredient in the composition, as described herein below. In some embodiments, the basic amine is nicotine or a nicotine component. By "nicotine component" is meant any suitable form of nicotine (e.g., free base, salt, or ion pair) to provide oral absorption of at least a portion of the nicotine present. Nicotine is released from the composition and absorbed through the oral mucosa, thereby entering the bloodstream, where it is circulated systemically.

[0111] When present as a basic amine, the source of nicotine may vary and may be natural or synthetic. The nicotine may be tobacco derived (e.g., tobacco extract) or non-tobacco derived (e.g., synthetically or otherwise obtained). Most preferably, the nicotine is natural and obtained as an extract from Nicotiana species (e.g., tobacco). The nicotine may 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, on a weight basis, of greater than about 95 percent, more preferably greater than about 98 percent, and most preferably greater than about 99 percent.

[0112] Typically, the nicotine component is selected from the group consisting of nicotine free base, nicotine as an ion pair, and a nicotine salt. In some embodiments, at least a portion of the nicotine is present in its free base form. In some embodiments, at least a portion of the nicotine is present as a nicotine salt, or at least a portion of the nicotine is present as an ion pair with at least a portion of an organic acid or its conjugate base, as disclosed herein above.

[0113] Typically, the nicotine component (calculated as the free base) is present in a concentration of at least about 0.001% by weight of the composition, such as in the range of about 0.001% to about 10%. In some embodiments, the nicotine component, calculated as the free base, is present in a concentration of about 0.1% w / w to about 10% by weight, such as, for example, about 0.1% w / w, about 0.2% by weight, about 0.3% by weight, about 0.4% by weight, about 0.5% by weight, about 0.6% by weight, about 0.7% by weight, about 0.8% by weight, or about 0.9% by weight, up to about 1% by weight, about 2% by weight, about 3% by weight, about 4% by weight, about 5% by weight, about 6% by weight, about 7% by weight, about 8% by weight, about 9% by weight, or about 10% by weight, based on the total weight of the composition. In some embodiments, the nicotine component is present in a concentration of from about 0.1% w / w to about 3% by weight, calculated as the free base, based on the total weight of the composition, such as from about 0.1% w / w to about 2.5% by weight, from about 0.1% by weight to about 2.0% by weight, from about 0.1% by weight to about 1.5% by weight, or from about 0.1% by weight to about 1% by weight.

[0114] As described herein above, the basic amine present in the composition may be nicotine or a nicotine component, or may be a component of an active ingredient or an active ingredient that contains a basic amine functional group. Those skilled in the art will recognize that many active ingredients described herein below are composed of molecules that can be classified as basic amines. Thus, ion pairing of such basic amine-containing active ingredients with lipophilic organic acids described herein is contemplated. In such embodiments, ion pairing of active ingredients with organic acids, alkali metal salts of organic acids, or combinations thereof can increase the stability of compositions containing ion pairs, or increase the absorption of active ingredients by oral mucosa due to the presence of the active ingredients in ion-paired form.

[0115] Filler The compositions described herein include at least one filler, which may serve multiple functions such as enhancing certain sensory properties such as texture and mouthfeel, enhancing the cohesiveness or compressibility of the product, etc.

[0116] Generally, the filler is a porous particulate material and is cellulose-based. For example, suitable fillers are any non-tobacco plant material or derivatives thereof, including cellulose materials derived from such sources. Examples of cellulosic non-tobacco plant materials include grains (e.g., maize, 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 cellulosics, and modified cellulosics.

[0117] "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 can 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 the 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, the main sources of starch include cereals (e.g. rice, wheat and maize) and root vegetables (e.g. potato and cassava). Other examples of starch sources include acorns, arrowroot, arracacha, banana, barley, legumes (e.g., broad beans, lentils, mung beans, peas, chickpeas), breadfruit, buckwheat, canna, chestnut, colacasia, dogtooth violet, kudzu, malanga, foxtail 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 undergo one or more structural changes, often designed to alter their high thermal properties. Some starches have been developed by genetic modification and are considered "modified" starches. Other starches are obtained and subsequently processed. For example, modified starches can be starches that have 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, enzyme treatment, acetylation, hydroxypropylation, and / or partial hydrolysis. Other starches are processed by heat treatments such as pregelatinization, dextrinization, and / or cold water swelling processes.Certain modified starches include phosphorylated monostarch, glycerol cross-linked starch, phosphate cross-linked starch esterified with sodium trimetaphosphate, phosphorylated phosphate cross-linked starch, acetylated phosphate cross-linked starch, starch acetate esterified with acetic anhydride, starch acetate esterified with vinyl acetate, acetylated adipate cross-linked starch, acetylated glycerol cross-linked starch, hydroxypropyl starch, hydroxypropylglycerol cross-linked starch, and sodium starch octenylsuccinate.

[0118] Additional examples of potential fillers include maltodextrin, dextrose, calcium carbonate, calcium phosphate, lactose, and sugar alcohols. A combination of fillers may also be used. In some embodiments, the filler comprises or is a mixture of glucose and starch-derived polysaccharides. One such suitable mixture of glucose and starch-derived polysaccharides is EMDEX®, available from JRS PHARMA LP, USA, 2981 Route 22, Patterson, NY 12563-2359.

[0119] In some embodiments, the particulate filler is a cellulose material or a cellulose derivative. One particularly suitable particulate filler for use in the compositions 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 mixtures thereof. In one embodiment, the composition includes mcc as a particulate filler. The amount of mcc present can vary depending on the desired properties.

[0120] The amount of filler can vary, but is typically up to about 75 percent of the composition by weight, based on the total weight of the composition. A typical range of filler (e.g., mcc) in the composition can be from about 10 to about 75 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 percent by weight (e.g., about 20 to about 50 percent by weight or about 25 to about 45 percent by weight), based on the total weight of the composition. In certain embodiments, the amount of filler is at least about 10 percent by weight, such as at least about 20 percent, or at least about 25 percent, or at least about 30 percent, or at least about 35 percent, or at least about 40 percent, based on the total weight of the composition.

[0121] In one embodiment, the filler further comprises a cellulose derivative or a combination of such derivatives. In some embodiments, the composition comprises about 1 to about 10% by weight of the cellulose derivative, and certain embodiments comprise about 1 to about 5% by weight of the cellulose derivative, based on the total weight of the composition. 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 by 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 composition comprises about 1 to about 3% by weight of HPC, based on the total weight of the composition.

[0122] water The water content of the composition may vary depending on the desired properties before use by the user of the composition. Typically, the composition is less than about 60 weight percent water, generally about 1 to about 60 weight percent water, such as about 5 to about 55 weight percent, about 10 to about 50 weight percent, about 20 to about 45 weight percent, or about 25 to about 40 weight percent water, including at least about 5 weight percent, at least about 10 weight percent, at least about 15 weight percent, and at least about 20 weight percent water. In some embodiments, the composition is less than about 10 weight percent water, such as about 9 weight percent or less, about 7 weight percent or less, about 5 weight percent or less, about 4 weight percent or less, about 3 weight percent or less, or about 2 weight percent or less. In some embodiments, the water content of the composition is in the range of about 0.1 weight percent to about 10 weight percent based on the total weight of the composition.

[0123] active ingredient The compositions disclosed herein, in certain embodiments, include an active ingredient. As used herein, "active ingredient" refers to one or more substances that belong to any of the following categories: API (active pharmaceutical substance), food additive, natural drug, and naturally derived substances that may have an action on humans. Exemplary active ingredients include any ingredient known to affect one or more biological functions in the body, such as ingredients that provide pharmacological activity or other direct action 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 effect, an antipyretic or analgesic effect, or have other effects that are beneficial to the body). In some embodiments, the active ingredient may be of the type commonly referred to as a dietary supplement, functional food, "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 not classified or regulated as drugs, and are normally available from naturally derived sources (e.g., botanical materials).

[0124] Non-limiting examples of 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 B6, B12 and C, and / or cannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD)). Each of these categories is further described herein below. The particular choice of active ingredient will depend on the desired flavor, texture and desired characteristics of a particular product.

[0125] The specific percentage of active ingredients present will vary depending on the desired characteristics of the particular product. Typically, the active ingredient or combination thereof is present 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% by weight. In some embodiments, the 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% by weight, about 1% to about 10% by weight, or about 1% to about 5% by weight, based on the total weight of the composition. In some embodiments, the active ingredient or combination of active ingredients is present in an amount of from about 0.001%, about 0.01%, about 0.1% or about 1% by weight, 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 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.08%, about 0.09%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, 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% by weight 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. More suitable ranges for certain active ingredients are provided herein below.

[0126] Botanical In some embodiments, the active ingredient comprises a botanical ingredient. As used herein, the term "botanical ingredient" or "botanical" refers to any plant or fungal 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 the purposes of this disclosure, "botanical" includes, but is not limited to, "herbal materials," which refer to seed-bearing plants that do not produce persistent woody tissue and are often valued for their medicinal or sensory properties (e.g., tea or herbal tea). When referring to "non-tobacco" botanical materials, tobacco materials are intended to be excluded (i.e., not including any Nicotiana species).

[0127] 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 foamable composition.

[0128] Botanical materials useful in the present disclosure can include any of the compounds and sources described herein, including, without limitation, mixtures thereof. Certain botanical materials of this type are sometimes referred to as dietary supplements, functional foods, "phytochemical agents" or "nutraceuticals." Certain botanicals find use in traditional herbal medicines as botanical materials or botanical extracts, and are further described herein.

[0129] Non-limiting examples of non-tobacco botanical materials include, but are not limited to, acai berry (Euterpe oleracea martius), acerola (Malpighia glabra), alfalfa, allspice, angelica root, anise (e.g., star anise), annatto seed, apple (Malus domestica), apricot oil, ashwagandha, bacopa monniera, baobab, basil (Ocimum basilicum), bay laurel, bee balm, beet root, bergamot, blackberry (Morus nigra), black cohosh, black pepper, black tea, blueberry, boldo (Peumus boldus), borage, ambrosia, cacao, calamus root, cam (Myrcaria dubia), hemp / cannabis, caraway seed, cardamom, blackcurrant, catnip, catuaba, cayenne pepper, Centella asiatica, chaga mushroom, chai fu, chamomile, cherry blossom, chervil, chives, chlorophyll, chocolate, coriander, cinnamon (Cinnamomum cassia), citron grass (Cymbopogon citratus), citrus, clary sage, clove, coconut (Cocos nucifera) nucifera), coffee, comfrey leaves and roots, cordyceps, coriander seed, cranberry, cumin, curcumin, damiana, dandelion, Dorstenia arifolia, Dorstenia odorata, echinacea, elderberry, elderflower, endro (Anethum graveolens), evening primrose, eucalyptus, fennel, feverfew, flax, Galphimia glaucaglauca), garlic, ginger (Zingiber officinale), ginkgo, carrot, goji berry, goldenseal, grape seed, grapefruit, pink grapefruit (Citrus paradisi), graviola (Annona muricata), green tea, guarana, gotu kola, hawthorn, hazel, hemp, hibiscus flower (Hibiscus sabdariffa), honeybush, hops, gynostemma, jambu (Spilanthes oleraceae), jasmine (Jasminum officinale), juniper berry (Juniperus communis), Kaempferia parviflora parviflora (turmeric), birch, laurel, lavender, lemon (Citrus limon), lemon balm, lemongrass, licorice, lilac, Yamabushitake, lutein, maca (Lepidium meyenii), mace, origanum vulgare, matcha, milk thistle, mint (mantle), mulberry, Nardostachys chinensis, nutmeg, olive, oolong tea, orange (Citrus sinensis), oregano, papaya, paprika, pennyroyal, peppermint (Mentha piperita), pimento, potato skin, evening primrose, quercetin, quince, red clover, resveratrol, Rhizoma gastrodiae gastrodiae, Rhodiola, Rooibos (red or green), Rosehips (Rosa canina), Rosemary, Saffron, Sage, St. John's Wort, Sandalwood, Salvia (Salvia officinalis), Savory, Saw Palmetto, Sceletium Tortuosumtortuosum, Schisandra chinensis, silybummarianum, skullcap, spearmint, spikenard, spirulina, slippery elm bark, sorghum bran high tannin, sorghum seed high tannin, spearmint (Mentha spicata), spirulina, star anise, sumac bran, tarragon, thyme, herbal tea, turmeric, Turnera aphrodisiaca, uva ursi, valerian, vanilla, Viola odorata, wild yam root, wintergreen, ashwagandha, yacon root, yellow dock, yerba mate, and yerba santa.

[0130] 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 stimulating 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 includes caffeine. In some embodiments, the active ingredient is 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.

[0131] When present, the stimulant or combination of stimulants (e.g., caffeine, theacrine, 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.

[0132] 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 either not naturally found in proteins or is not produced directly by the 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.

[0133] The amino acid or combination of amino acids (e.g., taurine, theanine, and combinations thereof), when present, is typically 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 effervescent composition.

[0134] Vitamins and Minerals 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. In some embodiments, the active ingredient includes one or more of vitamins B6 and B12. In some embodiments, the active ingredient includes theanine and one or more of vitamins B6 and B12.

[0135] If present, the vitamin or combination of vitamins (e.g., vitamin B6, vitamin B12, vitamin E, vitamin C or combinations thereof) will typically be at a concentration of about 0.01% w / w to about 1% by weight, for example, from 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%, or about 0.1 w / w%, to about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, or about 1 wt%, based on the total weight of the composition.

[0136] In some embodiments, the active ingredient comprises Vitamin A. In some embodiments, the Vitamin A is encapsulated. In some embodiments, the vitamin is Vitamin B6, Vitamin B12, Vitamin E, Vitamin C, or a combination thereof.

[0137] In some embodiments, the active ingredient comprises a mineral. As used herein, the term "mineral" refers to an inorganic molecule (or set of related molecules) that is an essential micronutrient required for the proper functioning of various systems in mammals. Non-limiting examples of minerals include iron, zinc, copper, selenium, chromium, cobalt, manganese, calcium, phosphorus, sulfur, magnesium, and the like. In some embodiments, the active ingredient comprises iron. Suitable iron sources include, but are not limited to, ferrous salts, such as ferrous sulfate and ferrous gluconate. In some embodiments, the iron is encapsulated.

[0138] Cannabinoids In some embodiments, the active ingredient comprises one or more cannabinoids. As used herein, the term "cannabinoid" refers to a class of diverse natural or synthetic chemical compounds that act on intracellular cannabinoid receptors (i.e., CB1 and CB2) to alter neurotransmitter release in the brain. Cannabinoids are cyclic molecules that exhibit certain properties, such as the ability to easily cross the blood-brain barrier. Cannabinoids can be naturally derived from plants, such as cannabis (phytocannabinoids), from animals (endocannabinoids), or artificially produced (synthetic cannabinoids). Cannabis species express at least 85 different phytocannabinoids, including cannabigerol, cannabichromene, cannabidiol, tetrahydrocannabinol, cannabinol and cannabinodiol, as well as other cannabinoids such as cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), and cannabinodiol (CBDL), cannabicyclol ( Cannabinol can be divided into subclasses including: cannabivarin (CBV), tetrahydrocannabivarin (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).

[0139] In some embodiments, the cannabinoid is selected from the group consisting of cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN) and cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabidiol (CBO), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarinic acid (THCV A), and mixtures thereof. In some embodiments, the cannabinoid comprises at least tetrahydrocannabinol (THC). In some embodiments, the cannabinoid is tetrahydrocannabinol (THC). In some embodiments, the cannabinoid comprises at least cannabidiol (CBD). In some embodiments, the cannabinoid is cannabidiol (CBD). In some embodiments, the CBD is synthetic CBD.

[0140] In some embodiments, the cannabinoid (e.g., CBD) is added to the composition in the form of an isolate, which is an extract from a plant, e.g., cannabis, in which the active substance of interest (in which case the cannabinoid, e.g., CBD) is present at a high degree of purity, e.g., greater than 95%, greater than 96%, greater than 97%, greater than 98%, or around 99% purity.

[0141] In some embodiments, the cannabinoid is a highly pure isolate of CBD and the amount of any other cannabinoid in the composition is about 1% or less by weight of the composition, such as about 0.5% or less by weight of the composition, such as about 0.1% or less by weight of the composition, such as about 0.01% or less by weight of the composition.

[0142] The selection of cannabinoids and the specific percentages thereof that may be present in the disclosed compositions will vary depending on the desired flavor, texture, and other characteristics of the composition.

[0143] In some embodiments, the cannabinoid (such as CBD) is present in the composition at a concentration of at least about 0.001% by weight of the composition, such as in the range of about 0.001% to about 2% by weight of the composition. In some embodiments, the cannabinoid (such as CBD) is present in the composition at a concentration of about 0.1% to about 1.5% by weight, based on the total weight of the composition. In some embodiments, the cannabinoid (such as CBD) is present in a concentration of about 0.4% to about 1.5% by weight, based on the total weight of the oral composition.

[0144] Alternatively, or in addition to cannabinoids, the active ingredient may include cannabis analogues, which are 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. Such compounds may be used in the same amounts and in the same ratios as specified herein for cannabinoids.

[0145] Terpenes Active ingredients suitable for use in the present disclosure may also be classified as terpenes, many of which are associated with biological effects, such as sedative effects. Terpenes have the general formula (C5H8): nTerpenes are considered to have the formula: ##STR1## 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.

[0146] In some embodiments, the terpene is a terpene derivable from a phytocannabinoid-producing plant, such as a plant of the Cannabis sativa species, e.g., a strain of cannabis. Suitable terpenes in this context include so-called "C10 terpenes" (such terpenes containing 10 carbon atoms) and so-called "C15 terpenes" (such terpenes containing 15 carbon atoms). In some embodiments, the active ingredient comprises more than one terpene. For example, the active ingredient may comprise one, two, three, four, five, six, seven, eight, nine, ten, or more terpenes as defined herein. In some embodiments, the terpene is selected from pinene (alpha and beta), geraniol, linalool, limonene, carvone, eucalyptol, menthone, iso-menthone, piperitone, myrcene, beta-bourbonene, germacrene, and mixtures thereof.

[0147] 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.

[0148] 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, erinaceus herb, 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, 12 (2005) pp. 216-220, incorporated herein by reference.

[0149] 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.

[0150] When present, antioxidants are typically at a concentration of about 0.001% w / w to about 10% by weight, for example, about 0.001% w / w, about 0.005% w / w, 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% by weight, based on the total weight of the composition.

[0151] 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.

[0152] If present, the amount of API may vary. For example, if present, the API is typically present in an amount of from about 0.001% w / w to about 10% 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%, about 0.07 w / w%, about 0.08 w / w%, about 0.09 w / w%, about 0.1% w / w, based on the total weight of the composition. w, 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%, to about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt%.

[0153] Encapsulation and stabilization of active ingredients In some embodiments, the active ingredients described herein may be susceptible to degradation (e.g., oxidation, photolysis, heat, evaporation) during processing or storage of the composition. In such embodiments, the active ingredients (such as caffeine, vitamin A, and iron (Fe)) may be encapsulated or the composition may be otherwise modified with appropriate components (fillers, binders, etc.) to achieve enhanced stability of the active ingredients. For example, binders such as functional celluloses (e.g., cellulose ethers, including but not limited to hydroxypropyl cellulose) or alginate-based materials (e.g., cross-linked alginates) may be used to enhance the stability of such actives against degradation or to achieve sustained and / or individualized delivery of the active ingredients. Additionally, the encapsulated actives may need to be paired with excipients in the composition to increase their solubility and / or bioavailability. Non-limiting examples of suitable excipients include beta-carotene, lycopene, vitamin D, vitamin E, coenzyme Q10, vitamin K, and curcumin.

[0154] In other embodiments, the initial amount of active ingredient may be increased to compensate for losses that occur over time due to decomposition to provide a desired concentration by weight of active ingredient, and thus initial amounts greater than those disclosed herein are contemplated by the present disclosure.

[0155] Flavoring Agent In some embodiments, the compositions described herein include a flavoring agent. As used herein, a "flavoring agent" or "flavoring agent" is any flavorful or fragrant substance that can modify the sensory properties associated with an oral product. Examples of sensory properties 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 properties can be described as fresh, sweet, herbal, confectionery, floral, fruity, or spicy, without limitation.

[0156] The flavoring agent may be an imitation, synthetic or natural ingredient, or a blend thereof. The flavoring agent may be a natural flavoring substance, a botanical, an extract of a botanical, a synthetically derived substance, or a combination thereof (e.g., tobacco, hemp, licorice (liquorice), hydrangea, eugenol, white bark magnolia leaf, chamomile, fenugreek, clove, maple, matcha, menthol, Japanese peppermint, aniseed (anise), cinnamon, turmeric, Indian spices, Asian spices, herbs, wintergreen, cherry, berry, red berry, cranberry, peach, apple, orange, Mango, clementine, lemon, lime, tropical fruits, papaya, rhubarb, grapes, durian, dragon fruit, cucumber, blueberry, mulberry, citrus, Drambuie, bourbon, scotch, whiskey, gin, tequila, rum, spearmint, peppermint, lavender, aloe vera, cardamom, celery, cascarilla, nutmeg, sandalwood, bergamot, geranium, hut, naswar, betel quid, shisha, pine, honey essence, rose oil, vanilla, lemon oil, orange oil, orange Flowers of the genus Mentha, cherry blossom, cassia, caraway, cognac, jasmine, ylang-ylang, sage, fennel, wasabi, pimento, ginger, coriander, coffee, hemp, peppermint oil of any species of the genus Mentha, eucalyptus, star anise, cocoa, lemongrass, rooibos, flax, ginkgo, hazel, hibiscus, laurel, yerba mate, orange peel, rose, tea such as green or black tea, thyme, juniper, elderflower, basil, bay leaves, cumin, oregano, paprika, rosemary, saffron, lemongrass, lemon juice, lemon juice, lemon juice powder, lemon juice, lemon juice syrup ... monpeal, mint, beefsteak plant, curcuma, cilantro, myrtle, blackcurrant, valerian, pimento, mace, damien, oregano, olive, lemon balm, lemon basil, chives, ribeye, verbena, tarragon, limonene, thymol, camphene), flavor enhancers, bitter taste receptor site blockers, sensory receptor site activators or stimulators, sugars and / or sugar substitutes (e.g., sucralose, acesulfame potassium, aspartame, saccharin, cyclamate, lactose, sucrose, glucose,fructose, sorbitol or mannitol), and other additives such as charcoal, chlorophyll, minerals, botanicals or breath fresheners.

[0157] The flavoring agent may further include a flavor enhancer, a bitter taste receptor site blocker, a sensory receptor site activator or stimulator, and a trigeminal sensate. As used herein, "trigeminal sensate" refers to a flavoring agent that acts on the trigeminal nerve to produce sensations including warm, cold, tingling, and the like. Non-limiting examples of flavoring agents that are trigeminal sensates include capsaicin, citric acid, menthol, Sichuan button, erythritol, and cubebol. A suitable heat agent may be, but is not limited to, vanillyl ethyl ether, and a suitable cooling agent may be, but is not limited to, eucalyptol, or N-ethyl-p-menthane-3-carboxamide (WS-3).

[0158] The flavoring agent may be in any suitable form, for example, a liquid such as an oil, a solid such as a powder, or a gas. In some cases, the flavoring agent may be provided in a spray-dried or liquid form. In some embodiments, the liquid flavoring agent is disposed in or on (i.e., adsorbed or absorbed within or on) a porous particulate carrier, such as microcrystalline cellulose, which is then combined with other composition ingredients.

[0159] The amount of flavoring utilized in the composition may vary, but will typically be up to about 10% by weight, with certain embodiments being characterized by a flavoring content of at least about 0.1% by weight, such as from about 0.5 to about 10% by weight, from about 1 to about 5% by weight, or from about 2 to about 4% by weight, based on the total weight of the composition.

[0160] Taste modifiers To improve the organoleptic properties of the compositions disclosed herein, the compositions may include one or more taste modifiers ("taste modifiers") that can act, for example, to mask, modify, block or improve the taste of the compositions described herein. Non-limiting examples of such taste modifiers include analgesic or anesthetic herbs, spices, and flavors that produce a sensation of cooling (e.g., menthol, eucalyptus, mint), warmth (e.g., cinnamon), or pain (e.g., capsaicin). Certain taste modifiers fall into more than one overlapping category.

[0161] In some embodiments, the taste modifier modifies one or more of bitter, sweet, salty, or sour tastes. In some embodiments, the taste modifier targets pain receptors. In some embodiments, the composition includes an active ingredient that has a bitter taste and a taste modifier that masks or blocks the sensation of the bitter taste. In some embodiments, the taste modifier is a substance that targets pain receptors (e.g., vanilloid receptors) in the user's oral cavity, for example, to mask the bitter taste of another component (e.g., an active ingredient). Suitable taste modifiers include, but are not limited to, capsaicin, gamma-aminobutyric acid (GABA), adenosine monophosphate (AMP), lactisol, or combinations thereof.

[0162] Representative amounts of taste modifiers, if present, are about 0.01% by weight or more, about 0.1% by weight or more, or about 1.0% by weight or more, but usually comprise less than about 10% by weight of the total weight of the composition (e.g., from about 0.01%, about 0.05%, about 0.1% or about 0.5% by weight to about 1%, about 5% or about 10% by weight of the total weight of the composition).

[0163] salt In some embodiments, the composition may further comprise a salt (e.g., an alkali metal salt) typically used in an amount sufficient to impart desired sensory attributes to the composition. Non-limiting examples of suitable salts include sodium chloride, potassium chloride, ammonium chloride, flour salts, and the like.

[0164] Representative amounts of salt, if present, will typically comprise about 0.5 weight percent or more, about 1.0 weight percent or more, or about 1.5 weight percent or more, but 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 composition.

[0165] Sweetener To improve the sensory properties of the composition according to the present disclosure, one or more sweeteners may be added. 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 fructose, sucrose, glucose, maltose, mannose, galactose, lactose, stevia, honey, etc. Examples of artificial sweeteners include sucralose, isomaltulose, maltodextrin, saccharin, aspartame, acesulfame K, neotame, etc. In some embodiments, the sweetener comprises one or more sugar alcohols. Sugar alcohols are polyols derived from monosaccharides or disaccharides, with partial or complete hydrogenation. 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).In some embodiments, the sweetener is sucralose, acesulfame K, or combinations thereof.

[0166] The sweetener or combination of sweeteners, when present, may comprise from about 0.01 to about 20% or more of the composition by weight, for example, from about 0.01 to about 0.1, from about 0.1 to about 1, from about 1 to about 5, from about 5 to about 10, or from about 10 to about 20% by weight, based on the total weight of the composition. In some embodiments, the combination of sweeteners is present in a concentration of from about 0.01% to about 0.1% by weight of the composition, such as about 0.01, about 0.02, about 0.03, about 0.04, about 0.05, about 0.06, about 0.07, about 0.08, about 0.09, or about 0.1% by weight of the composition. In some embodiments, the combination of sweeteners is present at a concentration of about 0.1% to about 0.5% by weight of the composition, such as about 0.1, about 0.2, about 0.3, about 0.4, or about 0.5% by weight of the composition, In some embodiments, the combination of sweeteners is present at a concentration of about 1% to about 3% by weight of the composition.

[0167] Binder A binder (or combination of binders) may be used in certain embodiments. Typical binders may be organic or inorganic, or a combination thereof. Representative binders include povidone, sodium alginate, starch-based binders, pectin, carrageenan, pullulan, zein, and the like, and combinations thereof. The binder may be used in an amount sufficient to provide the composition with desirable physical characteristics and physical integrity. The amount of binder utilized in the present compositions may vary, but is typically up to about 30 weight percent, with certain embodiments being characterized by a binder content of at least about 0.1 weight percent, such as about 1 to about 30 weight percent, or about 5 to about 10 weight percent, based on the total weight of the composition.

[0168] Other suitable binders include gums, such as natural gums. As used herein, natural gums refer to polysaccharide materials of natural origin that have binding properties and are also useful as thickeners or gelling agents. 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 karaya, locust bean gum, gellan gum, and combinations thereof. When present, natural gum binder materials are usually present in an amount of up to about 5% by weight, for example, 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 composition.

[0169] Wetting Agent In certain embodiments, one or more humectants may be used in the composition.Examples of humectants include, but are not limited to, polyols such as glycerin, propylene glycol, etc. When included, humectants are usually provided in an amount sufficient to provide the composition with desired moisture characteristics.Furthermore, in some cases, humectants can provide the composition with desirable flow properties for deposition in a mold.

[0170] When present, the humectant typically comprises up to about 5% by weight of the composition (e.g., from about 0.5% to about 5% by weight). When present, a representative amount of humectant is from about 0.1% to about 1% by weight, or from about 1% to about 5% by weight, based on the total weight of the composition.

[0171] Buffer In certain embodiments, the composition of the present disclosure can include a pH adjusting agent or buffering agent. Examples of pH adjusting agents and buffering agents that can be used include, but are not limited to, metal hydroxides (e.g., alkali metal hydroxides, e.g., sodium hydroxide and potassium hydroxide), and other alkali metal buffers, e.g., metal carbonates (e.g., potassium carbonate or sodium carbonate), or metal bicarbonates, e.g., sodium bicarbonate. Non-limiting examples of suitable buffers include alkali metal acetates, glycinates, phosphates, glycerophosphates, citrates, carbonates, bicarbonates, borates, or mixtures thereof.

[0172] When present, the buffering agent is typically present in an amount of less than about 5 percent by weight of the composition, for example, from about 0.5% to about 5%, such as from about 0.75% to about 4% by weight, from about 0.75% to about 3% by weight, or from about 1% to about 2% by weight, based on the total weight of the composition.

[0173] Coloring agent Coloring agents can be used in an amount sufficient to provide the composition with desired physical characteristics. Natural or synthetic coloring agents may be used, such as natural or synthetic dyes, food grade coloring agents, and pharmaceutical grade coloring agents. Examples of coloring agents include various dyes and pigments, such as caramel coloring agent and titanium dioxide. Natural coloring agents, such as curcumin, beet juice extract, spirulina, as well as various synthetic pigments, may also be used. The amount of coloring agent utilized in the composition may vary, but when present, is usually about 0.1% by weight, about 0.5% by weight, or about 1% to about 3% by weight, based on the total weight of the composition.

[0174] Tobacco Materials In some embodiments, the composition may include tobacco material. The tobacco material may 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.

[0175] 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.

[0176] 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 can be grown hydroponically.

[0177] Various parts or portions of a plant of the Nicotiana species may be included in the compositions 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 leaf (lamina). The compositions disclosed herein may include processed tobacco parts or pieces, dry processed and aged tobacco in essentially natural lamina and / or stem form, tobacco extract, extracted tobacco pulp (e.g., using water as a solvent), or mixtures of the foregoing (e.g., mixtures of extracted tobacco pulp granulated, dry processed, and combined with aged natural tobacco lamina).

[0178] 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 is most preferably tobacco lamina or a mixture of tobacco lamina and stem, at least some of which are smoked. Some 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 optionally incorporate tobacco that is fermentable. See the types of tobacco processing techniques described in Atchley et al., PCT WO2005 / 063060, which is incorporated herein by reference.

[0179] 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, pieces of different sizes of granulated tobacco can be mixed together.

[0180] 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 parts 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 part 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 part 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 part thereof, or a moisture content resulting from drying the plant or part thereof. For example, powdered, pulverized, milled or milled plant pieces or parts 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.

[0181] For the preparation of oral compositions, harvested plants of Nicotiana species are usually subjected to a curing process. The tobacco materials incorporated in the compositions 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.

[0182] 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 foregoing.

[0183] 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 thereof (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.

[0184] 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, that type of treatment is useful when the original tobacco material is subjected to heat in the previously described processes.

[0185] In some embodiments, a type of tobacco material is first selected that is visually somewhat lighter in color than other tobacco materials (e.g., whitened or bleached). In certain embodiments, the tobacco pulp may be whitened according to any of the means known in the art. For example, bleached tobacco materials produced by various whitening methods using various bleaching or oxidizing agents and oxidation catalysts may 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. 1996 / 031255 to Giolvas and PCT Published Application No. 2018 / 083114 to Bjorkholm.

[0186] 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 bleached 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.

[0187] In some embodiments, the whitened tobacco material can be characterized by a lightened color (e.g., "whitened") as compared to untreated tobacco material. White color is often defined with reference to the International Commission on Illumination (CIE) chromaticity diagram. In certain embodiments, the whitened tobacco material can be characterized as being closer to pure white on the chromaticity diagram than untreated tobacco material.

[0188] In various embodiments, the tobacco material can be processed to extract soluble components of the tobacco material therefrom. "Tobacco extract" as used herein refers to isolated components of tobacco material extracted from solid tobacco pulp by a solvent that is contacted with the tobacco material in an extraction process. Various extraction techniques for tobacco materials can be used to obtain tobacco extracts and tobacco solid materials. See, for example, the extraction process described in U.S. Patent Application Publication No. 2011 / 0247640 to Beeson et al., which is incorporated herein by reference.Other exemplary techniques for extracting tobacco components include those described in U.S. Pat. No. 4,144,895 to Fiore; U.S. Pat. No. 4,150,677 to Osborne, Jr. et al.; U.S. Pat. No. 4,267,847 to Reid; U.S. Pat. No. 4,289,147 to Wildman et al.; U.S. Pat. No. 4,351,346 to Brummer et al.; U.S. Pat. No. 4,359,059 to Brummer et al.; U.S. Pat. No. 4,506,682 to Muller; U.S. Pat. No. 4,589,428 to Keritsis; and U.S. Pat. No. 4,589,428 to Soga et al., all of which are incorporated herein by reference. No. 4,605,016 to Poulose et al.; U.S. Patent No. 4,716,911 to Niven, Jr. et al.; U.S. Patent No. 4,727,889 to Bernasek et al.; U.S. Patent No. 4,887,618 to Clapp et al.; U.S. Patent No. 4,941,484 to Clapp et al.; U.S. Patent No. 4,967,771 to Fagg et al.; U.S. Patent No. 4,986,286 to Roberts et al.; U.S. Patent No. 5,005,593 to Fagg et al.; U.S. Patent No. 5,018,540 to Grubbs et al.; U.S. Patent No. 5,060,669 to White et al.; U.S. Patent No. 5,070,671 to Fagg et al. No. 5,065,775; U.S. Patent No. 5,074,319 to White et al.; U.S. Patent No. 5,099,862 to White et al.; U.S. Patent No. 5,121,757 to White et al.; U.S. Patent No. 5,131,414 to Fagg; U.S. Patent No. 5,131,415 to Munoz et al.; U.S. Patent No. 5,148,819 to Fagg; U.S. Patent No. 5,197,494 to Kramer; U.S. Patent No. 5,230,354 to Smith et al.; U.S. Patent No. 5,234,008 to Fagg; U.S. Patent No. 5,243,999 to Smith; U.S. Patent No. 5,251,149 to Raymond et al. No. 5,301,694 to Gonzalez-Parra et al.; U.S. Pat. No. 5,318,050 to Teague; U.S. Pat. No. 5,343,879 to Newton; U.S. Pat. No. 5,360,022 to Newton; U.S. Pat. No. 5,435,325 to Clapp et al.; U.S. Pat. No. 5,445,169 to Brinkley et al.; U.S. Pat. No. 6,131,584 to Lauterbach; U.S. Pat. No. 6,298,859 to Kierulff et al.; U.S. Pat. No. 6,772,767 to Mua et al.; and U.S. Pat. No. 7,337,782 to Thompson.

[0189] Typical inclusion ranges for tobacco material can vary depending on the nature and type of tobacco material and the desired effect on the final mixture, with exemplary ranges being up to about 30% by weight (or up to about 20% by weight, or up to about 10% by weight, or up to about 5% by weight) (e.g., about 0.1 to about 15% by weight) based on the total weight of the composition. In some embodiments, compositions of the present disclosure can be characterized as being completely free or substantially free of tobacco material (other than purified nicotine as the active ingredient). For example, certain embodiments can be characterized as having less than 1% by weight, or less than 0.5% by weight, or less than 0.1% by weight tobacco material, or 0% by weight tobacco material.

[0190] Oral Care Additives In some embodiments, the composition includes an oral care ingredient (or a mixture of such ingredients) that provides the ability to prevent tooth decay or tooth loss, prevent gum disease, relieve oral pain, whiten teeth, or otherwise prevent tooth staining, induce saliva stimulation, prevent bad breath, freshen breath, etc. For example, effective amounts of ingredients such as thyme oil, eucalyptus oil, and zinc (such as ingredients of a formulation commercially available as ZYTEX® from Discus Dental) can be incorporated into the composition. Other examples of ingredients that may be included in the compositions of the present invention in desired effective amounts include those included in the types of oral care compositions described in Takahashi et al., Oral Microbiology and Immunology, Vol. 19(1), pp. 61-64 (2004); Thistle, U.S. Patent No. 6,083,527; and Jakubowski, U.S. Patent Application Publication No. 2006 / 0210488 and Cummins et al., U.S. Patent Application Publication No. 2006 / 02228308. Other exemplary ingredients of tobacco-containing formulations include those included in the formulations marketed as MALTISORB® by Roquette and DENTIZYME® by NatraRx. Representative amounts of oral care additives, when present, are at least about 1%, often at least about 3%, and frequently at least about 5% of the total dry weight of the foamable composition. The amount of oral care additive in the foamable composition typically does not exceed about 30%, often does not exceed about 25%, and frequently does not exceed about 20% of the total dry weight of the foamable composition.

[0191] Processing Aids If the composition requires downstream processing, such as granulation, mixing or molding, a flow aid can also be added to the composition to increase the flowability of the composition. In some embodiments, the composition (e.g., melt form and chewable form) can be surface treated with an anti-adhesive agent, such as oil, silicone, etc. Exemplary flow aids include microcrystalline cellulose, silica, polyethylene glycol, stearic acid, calcium stearate, magnesium stearate, zinc stearate, sodium stearyl fumarate, carnauba wax, and combinations thereof. In some embodiments, the flow aid is sodium stearyl fumarate.

[0192] A representative amount of flow aid, when present, can comprise at least about 0.5 percent or at least about 1 percent of the total dry weight of the composition. Preferably, the amount of flow aid in the composition does not exceed about 5 percent, and frequently does not exceed about 3 percent, of the total dry weight of the composition.

[0193] Other Additives Other additives may be included in the disclosed compositions. For example, the compositions are processed, blended, compounded, 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 additional types of additives include thickening or gelling agents (e.g., fish gelatin), emulsifiers, preservatives (e.g., potassium sorbate, etc.), 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. Pat. No. 9,237,769 to Mua et al., U.S. Pat. No. 7,861,728 to Holton, Jr. et al., U.S. Pat. App. Pub. No. 2010 / 0291245 to Gao et al., and U.S. Pat. App. Pub. No. 2007 / 0062549 to Holton, Jr. et al., each of which is incorporated herein by reference.

[0194] Typical inclusion ranges for such additional additives can vary depending on the nature and function of the additive and its intended effect on the final composition, with an exemplary range 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 composition.

[0195] The above-mentioned additives can be used 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 when provided in the final product or composition. Exemplary encapsulated additives are described, for example, in WO 2010 / 132444 to Atchley, which has already been incorporated by reference herein.

[0196] fine particles In some embodiments, one or more of the fillers, the tobacco material, other components of the composition, and the overall composition described herein may be described as a particulate material. 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 agglomerates of a plurality of particles, the particles having an average length to width ratio of less than 2:1, such as less than about 1:1, such as less than 1.5:1. In various embodiments, the particles of the particulate material may be described as substantially spherical or granular.

[0197] The particle size of a particulate material can be measured by sieve analysis. As one skilled in the art will readily appreciate, sieve analysis (otherwise known as gradient testing) is a method used to measure the particle size distribution of particulate materials. Typically, sieve analysis involves a column of nested sieves, with the sieves preferably comprising a screen in the form of a wire mesh fabric. A pre-weighed sample can be introduced into the top or uppermost sieve in the column, which has the largest screen opening or mesh size (i.e., the largest pore size of the sieve). Each sieve lower in the column has a screen opening or mesh size that is progressively smaller than the sieve above it. Typically, the bottom of the column of sieves is a receiver section for collecting any particles having a particle size smaller than the screen opening or mesh size of the bottom or lowest sieve in the column (which has the smallest screen opening or mesh size).

[0198] In some embodiments, the column of sieves may be placed on or in a mechanical shaker. The shaker creates vibrations on each of the sieves in the column. The mechanical shaker may be run for a predetermined period of time to ensure that all particles are collected on the correct sieve. In some embodiments, the column of sieves is shaken for a period of time between 0.5 minutes and 10 minutes, such as between 1 minute and 10 minutes, such as between 1 minute and 5 minutes, such as approximately 3 minutes. Once the shaking of the sieves in the column is complete, the material collected on each sieve is weighed. The weight of each sample on each sieve can then be divided by the total weight to obtain the mass percentage retained on each sieve. As one skilled in the art will readily recognize, the screen opening size or mesh size for each sieve in the column used for sieve analysis may be selected based on the particle size of the sample to be analyzed or the known maximum / minimum particle size. In some embodiments, a column of sieves may be used for sieve analysis, the column comprising 2 to 20 sieves, such as 5 to 15 sieves. In some embodiments, a column of sieves may be used for sieve analysis, the column comprising 10 sieves. In some embodiments, the maximum screen opening or mesh size of the sieve used for sieve analysis may be 1000 μm, such as 500 μm, such as 400 μm, such as 300 μm.

[0199] In some embodiments, any particulate material (e.g., filler, tobacco material, and total composition) referred to herein can be characterized as having at least 50% by weight of particles having a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis. In some embodiments, at least 60% by weight of particles of any particulate material referred to herein have particles having a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis. In some embodiments, at least 70% by weight of particles of any particulate material referred to herein have particles having a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis. In some embodiments, at least 80% by weight of the particles of any particulate material referred to herein have particles having a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis. In some embodiments, at least 90% by weight of the particles of any particulate material referred to herein have particles having a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis. In some embodiments, at least 95% by weight of the particles of any particulate material referred to herein have particles having a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis. In some embodiments, at least 99% by weight of the particles of any particulate material referred to herein have particles having a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis.In some embodiments, nearly 100% by weight of any particulate material referred to herein has particles having a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis.

[0200] In some embodiments, at least 50% by weight, such as at least 60% by weight, such as at least 70% by weight, such as at least 80% by weight, such as at least 90% by weight, such as at least 95% by weight, such as at least 99% by weight, of any particulate material referred to herein have a particle size of from about 0.01 μm to about 1000 μm, such as from about 0.05 μm to about 750 μm, such as from about 0.1 μm to about 500 μm, such as from about 0.25 μm to about 500 μm, as measured by sieve analysis. In some embodiments, at least 50% by weight, such as at least 60% by weight, such as at least 70% by weight, such as at least 80% by weight, such as at least 90% by weight, such as at least 95% by weight, such as at least 99% by weight, of any particulate material referred to herein have a particle size of from about 10 μm to about 400 μm, such as from about 50 μm to about 350 μm, such as from about 100 μm to about 350 μm, such as from about 200 μm to about 300 μm, as measured by sieve analysis.

[0201] Preparation of the Composition The manner in which the various components of the mixture are combined may vary. Thus, the overall mixture of the various components with, for example, the powder mixture components, may be relatively homogenous in nature. The above-mentioned components may be in liquid form or dry solid form and may be mixed in a pre-processing step prior to mixing with any remaining components of the mixture, or may simply be mixed together with all other liquid or dry components. The various components of the mixture may be contacted, combined, or mixed together using any mixing technique or device known in the art. Any mixing method may be used, such as a mixing device characterized by an impeller or other structure capable of stirring that brings the mixture components into intimate contact. 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. The manner and method of blending the mixture will be clear to those skilled in the art. 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, 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.

[0202] In some embodiments, the compositions may be prepared such that the composition mixture can be used in non-starch or starch-based molding processes. Exemplary types of molds that can be used in the production process include, for example, starch molds, non-starch molds, pectin molds, plastic tray molds, silicone tray molds, metal tray molds, neoprene tray molds, and the like.

[0203] Configured for the oral cavity Compositions that are adapted for oral use are provided herein. The term "adapted for oral use" as used herein means that the composition is provided in such a form that one or more components of the composition (e.g., basic amine, flavoring agent and / or active ingredient) are carried into the mouth of the user by the saliva in the user's mouth during use. In certain embodiments, the composition is adapted to deliver a component to the user via the mucous membrane in the user's oral cavity, the user's digestive system, or both, and in some cases, the component is a nicotine component or active ingredient (including, but not limited to, for example, nicotine, stimulants, vitamins, amino acids, botanicals, or combinations thereof) that can be absorbed via the mucous membrane in the oral cavity or absorbed via the digestive tract when the product is used.

[0204] The compositions configured for oral use described herein can take a variety of forms, including gels, pastilles, gums, chews, melts, tablets, lozenges, granules, powders, and pouches. Gels can be soft or hard. Certain compositions of the present disclosure are in solid form. Certain compositions can exhibit, for example, one or more of the following characteristics: crispy, granular, chewy, syrupy, pasty, fluffy, smooth, and / or creamy. In certain embodiments, the desired textural properties can be selected from the group consisting of adhesiveness, cohesiveness, density, dryness, friability, granularity, stickiness, hardness, weightiness, moisture absorption, moisture release, oral coating, grittiness, silkiness, smoothness, viscosity, wetness, and combinations thereof.

[0205] The compositions of the present disclosure may be soluble. As used herein, the terms "dissolve", "dissolving" and "soluble" refer to compositions having water-soluble components that interact with the moisture in the oral cavity to go into solution, thus causing gradual consumption of the composition. According to one aspect, a soluble composition can persist in the oral cavity of a user for a given time until it completely dissolves. 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 will usually dissolve and / or release the desired components (e.g., active ingredients, flavors, etc.) within about 2 minutes, often within about 1 minute (e.g., within about 50 seconds, within about 40 seconds, within about 30 seconds, or within about 20 seconds). 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 time the product remains in the oral cavity of the user.

[0206] The compositions disclosed herein may be formed into a variety of shapes, including round, tablet, sphere, strip, film, sheet, coin, cube, bead, egg, obloid, cylinder, bean, stick, or rod. The cross-sectional shape of the composition may vary, with example cross-sectional shapes including round, square, oval, rectangular, etc. Such shapes may be formed in a variety of ways using equipment such as moving belts, nips, extruders, granulators, compactors, etc.

[0207] Certain compositions adapted for oral use are in the form of pastels. As used herein, the term "pastel" refers to a soluble oral composition made by solidifying a liquid or gel composition, resulting in a somewhat hardened solid gel in the final composition. The stiffness of the gel can vary greatly. Pastel products may alternatively be referred to as soft lozenges. In certain embodiments, the pastel products of the present disclosure are characterized by sufficient cohesiveness to withstand mild chewing action in the oral cavity without disintegrating quickly. Pastel products of the present disclosure do not typically exhibit a highly deformable chewability, as typically found in conventional chewing gums.

[0208] In some embodiments, the products disclosed herein can be in the form of a dissolvable lozenge product adapted for oral use. Exemplary lozenge-type products of the present invention have the form of lozenges, tablets, microtabs, or other tablet-type products. For example, U.S. Patent No. 4,967,773 to Shaw; U.S. Patent No. 5,110,605 to Acharya; U.S. Patent No. 5,733,574 to Dam; U.S. Patent No. 6,280,761 to Santus; U.S. Patent No. 6,676,959 to Andersson et al.; U.S. Patent No. 6,248,760 and U.S. Patent No. 7,374,779 to Wilhelmsen; U.S. Patent Publication No. 2001 / 0016593 to Wilhelmsen, all of which are incorporated herein by reference. No. 2004 / 0101543 to Liu et al.; No. 2006 / 0120974 to Mcneight; No. 2008 / 0020050 to Chau et al.; No. 2009 / 0081291 to Gin et al., and No. 2010 / 0004294 to Axelsson et al., for types of nicotine-containing lozenges, lozenge formulations, lozenge formats and configurations, characteristics of the lozenges, and techniques for formulating or manufacturing the lozenges.

[0209] Lozenge products are generally described as "hard" and are distinguished as such from soft lozenges (i.e., pastilles). Hard lozenges are a mixture of sugars and / or carbohydrates in an amorphous state. Hard lozenges are made from an aqueous syrup, but the water initially present evaporates as the syrup boils during processing, resulting in a very low moisture content in the final product, such as 0.5-1.5% by weight. To obtain a hard, non-sticky lozenge, the melt temperature must generally reach the hard crack stage, an exemplary temperature range being 149°-154°C.

[0210] In some embodiments, the composition may be chewable, meaning that the composition has a light resilience or "bounce" upon chewing and a desired degree of malleability. The chewable form of the composition may be entirely soluble or in the form of a non-dissolving gum, in which case only certain components (e.g., active ingredients, flavors, sweeteners, etc.) dissolve, leaving behind a non-dissolving matrix. Chewable embodiments generally include a binder such as a natural gum or pectin. In some embodiments, the composition in chewable form includes pectin and an organic acid, with one or more sugar alcohols in an amount of at least 50% by weight, based on the total weight of the composition. Generally, the pectin is present in an amount of about 1 to about 3% by weight, based on the total weight of the composition.

[0211] In some embodiments, the composition may be meltable, as discussed, for example, in U.S. Patent Application No. 2012 / 0037175 to Cantrell et al., which is incorporated herein by reference in its entirety. As used herein, "melt", "melting" and "meltable" refer to the ability of a composition to change from a solid state to a liquid state. That is, melting occurs when a substance (e.g., a composition disclosed herein) changes from solid to liquid, usually by application of heat. The application of heat for the compositions disclosed herein is provided by the temperature in the user's mouth. Thus, the term "meltable" refers to a composition that can be liquefied in the user's mouth when the composition changes phase from solid to liquid, and is intended to be distinguished from a composition that simply disintegrates in the mouth due to loss of cohesion within the composition, which simply dissolves in the mouth when the water-soluble components of the composition interact with moisture. In general, meltable compositions include lipids, as described herein above. In some embodiments, the composition in meltable form comprises lipid in an amount of about 35 to about 50% by weight based on the total weight of the composition, and sugar alcohol in an amount of about 35 to about 55% by weight based on the total weight of the composition. In some embodiments, the sugar alcohol is isomalt, erythritol, sorbitol, arabitol, ribitol, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, or combinations thereof. In some embodiments, the sugar alcohol is isomalt.

[0212] In certain embodiments, the composition is in the form of compressed or molded pellets. Exemplary pellets range in weight from about 250 mg to about 1500 mg, such as from about 250 mg to about 700 mg, or from about 700 mg to about 1500 mg. The pellets can have any of a variety of shapes, including traditional pill or tablet shapes. Generally, the composition in tablet form comprises a glucose-polysaccharide blend and a sugar alcohol. In some embodiments, the glucose-polysaccharide blend is present in an amount of about 35 to about 50% by weight based on the total weight of the composition, and the sugar alcohol is present in an amount of about 30 to about 45% by weight based on the total weight of the composition. In some embodiments, the sugar alcohol is isomalt, erythritol, sorbitol, arabitol, ribitol, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, or a combination thereof. In some embodiments, the sugar alcohol is isomalt.

[0213] In one embodiment, the composition of the present disclosure is placed in a moisture-permeable container (e.g., a water-permeable pouch). The composition enclosed in the pouch may be in any desired form. In certain embodiments, the composition is in granular form. Such compositions in a water-permeable pouch format are typically used by placing one of the pouches containing the composition in the oral cavity of a human subject / user. In general, the pouch is placed somewhere in the oral cavity of the user, for example under the lips, in the same way that moist snuff products are typically used. As described herein below, unless the pouch composition or substance is ingestible (e.g., soluble or dispersible), the pouch is preferably not chewed or swallowed. Exposure to saliva then causes some of the components of the mixture therein (e.g., flavoring agent and / or nicotine), for example, to pass through the water-permeable pouch, providing the user with a flavor and a sense of satisfaction, without the user having to spit out 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 may be ingested by the human subject and the pouch may be removed from the human subject's mouth for disposal.

[0214] In some embodiments, the oral products provided herein may be in the form of a center-filled pastille or lozenge, for example, such that the interior (or at least a portion) of the product has one or more different organoleptic properties (e.g., texture, mouthfeel, taste, etc.) from its outer surface (or other portion). Such center-filled pastille or lozenge formulations may include a liquid and / or gel and / or meltable and / or chewable and / or gummy and / or effervescent center surrounded by a harder outer shell that may be associated with the pastille-type products or lozenge products described herein. In such embodiments, the center-fill may be described as less rigid and / or softer than the outer shell. In some embodiments, the center-fill may or may not include an active ingredient therein. For example, in some embodiments, both the outer shell and the center formulation may include an active ingredient to provide a sustained release of the active ingredient therefrom. In some embodiments, at least the outer shell formulation includes a pastille formulation as described herein above. In other embodiments, both the outer shell formulation and the core formulation may comprise pastel formulations described herein, with similar or different organoleptic properties.

[0215] Thus, in certain embodiments, the composition disclosed herein and any other components described above are combined in a water-permeable packet or pouch that serves as a container for using the composition to obtain a pouched product configured for oral cavity. Certain embodiments of the present disclosure are described with reference to FIG. 1 of the accompanying drawings, and these described embodiments include a snus-type product having an outer pouch and containing the mixture described herein. As described in more detail below, such embodiments are presented by way of example only, and the pouched product of the present disclosure can include other forms of composition. The mixture / composition of such a packet or pouch, such as the container pouch 102 in the embodiment illustrated in FIG. 1, can vary. Referring to FIG. 1, a first embodiment of a pouched product 100 is shown. The pouched product 100 includes a moisture-permeable container in the form of a pouch 102 that contains a material 104 that includes the composition described herein.

[0216] Suitable packet, pouch or container types used in the manufacture of smokeless tobacco products 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. The mixture may be packaged in a pouch in a manner and using the types of components used in the manufacture of conventional snus types of products. The pouch provides a liquid-permeable container of a type that may be considered similar in nature to the mesh-like type of material used in the construction of tea bags. The components of the mixture easily diffuse from the pouch into the mouth of the user.

[0217] Non-limiting examples of suitable types of pouches are described in, for example, U.S. Pat. Nos. 5,167,244 to Kjerstad and 8,931,493 to Sebastian et al., as well as U.S. Patent Application Publication Nos. 2016 / 0000140 to Sebastian et al., 2016 / 0073689 to Sebastian et al., 2016 / 0157515 to Chapman et al.; and 2016 / 0192703 to Sebastian et al., each of which is incorporated herein by reference. The pouches may be supplied as individual pouches or multiple pouches (e.g., 2, 4, 5, 10, 12, 15, 20, 25, or 30 pouches) may be strung or linked together (e.g., in an end-to-end manner) so that single patches or individual doses may be easily removed for use from the linked chain or matrix of pouches.

[0218] Exemplary pouches may be manufactured in such a manner from materials such that the pouch undergoes controlled dispersion or elution during use by a user. Such pouch materials may have the form of mesh, screen, perforated paper, permeable fabric, and the like. For example, pouch materials manufactured from rice paper or mesh-like forms of perforated rice paper can dissolve in the mouth of a user. As a result, the pouch and composition can each undergo complete dispersion in the mouth of a user during normal conditions of use, and thus both the pouch and the composition can be ingested by the user. Other examples of pouch materials may be manufactured using materials in combination with materials such as water-dispersible film-forming materials (e.g., binders such as alginates, carboxymethylcellulose, xanthan gum, pullulan, and the like), and ground cellulose derivatives (e.g., fine particle size wood pulp). Preferred pouch materials are water-dispersible or soluble, but can be designed and manufactured such that under normal conditions of use, a significant amount of the mixture's contents will permeate the pouch material before the pouch loses its physical integrity. If desired, flavor ingredients, disintegration aids and other desired components may be incorporated into or applied to the pouch material.

[0219] The amount of material placed in each product unit, e.g., pouch, can vary. In some embodiments, the weight of the composition in each pouch is at least about 50 mg, e.g., about 50 mg to about 1 gram, about 100 mg to about 800 mg, or about 200 mg to about 700 mg. In some smaller embodiments, the weight of the composition in each pouch can be about 100 mg to about 300 mg. For larger embodiments, the weight of the composition in each pouch can be about 300 mg to about 700 mg. If desired, other components can be placed in each pouch. 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) can be placed in each pouch, with or without at least one capsule. Such strip or sheet can be folded or clamped to facilitate incorporation into the pouch. See, for example, U.S. Pat. Nos. 6,887,307 to Scott et al. and 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) 85, pp. 1-32.

[0220] The pouched products described herein can be packaged in any suitable inner packaging material and / or outer container, for example, U.S. Patent Nos. 7,014,039 to Henson et al., 7,537,110 to Kutsch et al., 7,584,843 to Kutsch et al., 8,397,945 to Gelardi et al., D592,956 to Thiellier et al., D594,154 to Patel et al., and D625,178 to Bailey et al., U.S. Patent Publication Nos. 2008 / 0173317 to Robinson et al., 2009 / 0014343 to Clark et al., and 2009 / 001 to Bjorkholm, all of which are incorporated herein by reference. See also U.S. Patent Publication No. 4450 to Bellamah et al.; U.S. Patent Publication No. 2009 / 0250360 to Gelardi et al.; U.S. Patent Publication No. 2009 / 0266837 to Gelardi; U.S. Patent Publication No. 2009 / 0223989 to Gelardi; U.S. Patent Publication No. 2009 / 0230003 to Thiellier; U.S. Patent Publication No. 2010 / 0084424 to Gelardi; and U.S. Patent Publication No. 2010 / 0133140 to Bailey et al.; U.S. Patent Publication No. 2010 / 0264157 to Bailey et al.; and U.S. Patent Publication No. 2011 / 0168712 to Bailey et al.

[0221] Many modifications and other embodiments of the invention will come to mind to one skilled in the art to which this invention pertains 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 modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms have been employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation. EXAMPLES

[0222] Aspects of the present invention are more fully illustrated by the following examples, which are set forth to illustrate certain specific aspects of the invention and should not be construed as limiting the invention.

[0223] [Example 1] Nicotine-monomenthyl succinate ion pair solution (12% nicotine by weight) An ion pair solution was formed by mixing together 72 g of a 25% aqueous nicotine solution, 28.4 g of monomenthyl succinate, and 49.5 g of deionized water, such that the concentration of the nicotine-monomenthyl succinate ion pair, expressed as nicotine, in the solution was approximately 12% by weight.

[0224] [Example 2] Nicotine-monomenthyl succinate ion pair solution (18% nicotine by weight) An ion pair solution was formed by mixing together 114.7 g of a 25% aqueous nicotine solution and 45.3 g of monomenthyl succinate, such that the concentration of the nicotine and monomenthyl succinate ion pair, expressed as nicotine, in the solution was about 18% by weight.

[0225] [Example 3] Nicotine-tocopherol succinate ion pair solution (9% nicotine by weight) An ion pair solution was formed by mixing 72 g of a 25% aqueous nicotine solution, 58.9 g of tocopherol succinate, and 69 g of propylene glycol. The concentration of the nicotine-tocopherol succinate ion pair, expressed as nicotine, in the solution was about 9% by weight.

[0226] Example 4: Additional nicotine ion pair solutions The ion pair solution is formed by mixing a 25% aqueous solution of nicotine with monomenthyl glutarate, bixin or norbixin according to the procedures of Examples 1-3. A solubility enhancer, such as glycerol, propylene glycol or other suitable solvent, may be added to increase the solubility of the ion pair in the solution. The concentration of the nicotine-organic acid ion pair, expressed as nicotine, in the solution may vary.

[0227] [Example 5] Isomalt syrup base The isomalt syrup base is made by combining 1437 g of isomalt powder, 15.2 g of a 75% aqueous solution of maltitol, 21 g of sodium chloride, 75 g of deionized water, and 0.5 g of sucralose and heating the mixture to 160°C.

[0228] Example 6: Lozenges containing nicotine-monomenthyl succinate ion pair An isomalt-based lozenge was prepared by mixing 0.91 g of the ion pairing solution of Example 2 with 154.7 g of the isomalt syrup of Example 5 at a temperature of about 285° F. The hot mixture was poured into a metal mold to obtain individual pieces weighing about 1.9 g and containing about 2 mg of nicotine (free base basis) as the nicotine-monomenthyl succinate ion pair. The individual pieces were allowed to cool to room temperature. The lozenges exhibited good clarity. Qualitatively, upon oral dissolution, the lozenges exhibited little oral and pharyngeal irritation.

[0229] Example 7: Pouched product containing nicotine-tocopherol succinate ion pair A pouched oral product containing a nicotine-tocopherol succinate ion pair composition is prepared according to the formula in Table 2. The microcrystalline cellulose and salt are blended together. The nicotine and tocopherol succinate ion pair solution of Example 3 is combined with the nicotine benzoate ion pair solution (12% nicotine), sweetener, and deionized water. The mixture is combined with the previously prepared microcrystalline cellulose and salt blend to obtain a composition. The pouched oral product is made by transferring the composition to a pouch filler, adding the pouch filler contents to a nonwoven fleece, and heat sealing the fleece. The final pouched product contains about 494 mg of the composition. Water is added to the pouch to obtain a final weight of about 588 mg. The nicotine content of each pouch in the form of nicotine benzoate and nicotine tocopherol succinate ion pair is about 6.0 mg based on free base nicotine.

[0230] [Table 2]

[0231] [Example 8] Pouched product containing nicotine-monomenthyl succinate ion pair A pouched oral product containing a nicotine-monomenthyl succinate ion pair composition is prepared according to the formula in Table 3. The microcrystalline cellulose and salt are blended together. The nicotine and monomenthyl succinate ion pair solution of Example 2 is combined with the nicotine benzoate ion pair solution (12% nicotine), sweetener, and deionized water. The mixture is combined with the previously prepared microcrystalline cellulose and salt blend to obtain a composition. The pouched oral product is made by transferring the composition to a pouch filler, adding the pouch filler contents to a nonwoven fleece, and heat sealing the fleece. The final pouched product contains about 494 mg of the composition. Water is added to the pouch to obtain a final weight of about 588 mg. The nicotine content of each pouch in the form of nicotine benzoate and nicotine tocopherol succinate ion pair is about 6.0 mg based on free base nicotine.

[0232] [Table 3]

[0233] [Example 9] LogP determination of nicotine-monomenthyl succinate ion pair An aqueous ion pair solution consisting of 100 ppm nicotine and 2 molar equivalents of monomenthyl succinate was prepared and the pH was adjusted to 6.0. The log octanol-water partition coefficient (LogP) for the ion paired solution was determined to be 0.86. The positive partition coefficient means that the resulting ion pair is lipophilic and is therefore expected to result in increased absorption when a product containing such an ion pair is consumed.

Claims

1. At least one filler Basic amines Water, and 1. A composition adapted for oral use, comprising an organic acid, an alkali metal salt of an organic acid, or a combination thereof, wherein the organic acid has a log P value of 1 to 12; at least a portion of the basic amine is associated with at least a portion of the organic acid or the alkali metal salt thereof, the association being in the form of a basic amine-organic acid salt, an ion pair between the basic amine and a conjugate base of the organic acid, or both; and the organic acid is a monoester of a dicarboxylic acid or a carotenoid derivative having one or more carboxylic acids.

2. 2. The composition of claim 1, wherein the organic acid has a log P value of 3 to 12.

3. 2. The composition of claim 1, wherein the organic acid is a menthyl monoester of a dicarboxylic acid or a tocopherol monoester.

4. The composition of claim 3 , wherein the dicarboxylic acid is malonic acid, succinic acid, glutaric acid, adipic acid, fumaric acid, maleic acid, or a combination thereof.

5. 2. The composition of claim 1, wherein the organic acid is norbixin, bixin, or an isomer thereof.

6. 2. The composition of claim 1, wherein the organic acid is tocopherol succinate, monomenthyl succinate, monomenthyl fumarate, monomenthyl glutarate, or a combination thereof.

7. The composition of claim 1 , wherein the composition further comprises a solubility improver.

8. The composition of claim 7 , wherein the solubility improver is glycerol or propylene glycol.

9. 10. The composition of claim 1, comprising from 0.05 to 20 molar equivalents of the organic acid, the alkali metal salt thereof, or a combination thereof, relative to the basic amine, calculated as amine free base.

10. 10. The composition of claim 1, comprising 2 to 10 molar equivalents of the organic acid, the alkali metal salt thereof, or a combination thereof relative to the basic amine, calculated as amine free base.

11. The composition of claim 1 , wherein the organic acid further comprises benzoic acid, an alkali metal salt thereof, or a combination thereof.

12. 2. The composition of claim 1, wherein the alkali metal is sodium or potassium.

13. The composition of claim 1 comprising the organic acid and a sodium salt of the organic acid.

14. 14. The composition of claim 13, wherein the weight ratio of the organic acid to the sodium salt of the organic acid is 0.1 to 10.

15. 2. The composition of claim 1, wherein the pH of the composition is 4.0 to 9.

0.

16. 2. The composition of claim 1, wherein the pH of the composition is 4.5 to 7.

17. 10. The composition of claim 1, wherein the pH of the composition is 5.5 to 7.

18. The composition of claim 1, wherein the pH of the composition is 4.0 to 5.

5.

19. The composition of claim 1, wherein the pH of the composition is 7.0 to 9.

0.

20. The composition of claim 1 , wherein the basic amine is nicotine.

21. 21. The composition of claim 20, wherein the nicotine is present in an amount of 0.001 to 10% by weight of the composition, calculated as the free base, relative to the total weight of the composition.

22. The composition of claim 1 , wherein the at least one filler comprises a cellulosic material.

23. 23. The composition of claim 22, wherein the cellulosic material comprises microcrystalline cellulose.

24. The composition of claim 1, wherein the at least one filler further comprises a cellulose derivative in an amount of 1% to 3% by weight, based on the total weight of the composition.

25. 25. The composition of claim 24, wherein the cellulose derivative is hydroxypropyl cellulose.

26. 10 to 50% of said at least one filler, relative to the total weight of the composition; and 5 to 60% by weight of water The composition of claim 1 comprising:

27. 10. The composition of claim 1, further comprising one or more active ingredients, one or more flavoring agents, one or more salts, one or more sweetening agents, one or more binders, one or more humectants, one or more gums, tobacco materials, or combinations thereof.

28. 10. The composition of claim 1, further comprising one or more active ingredients selected from the group consisting of functional foods, botanicals, stimulants, amino acids, vitamins, and cannabinoids.

29. 10. The composition of claim 1, comprising no more than 10% by weight of tobacco material, excluding any nicotine component present, based on the total weight of the composition.

30. The composition of claim 1 , which is free of tobacco material.

31. the composition is enclosed within a pouch to form a pouch product; 31. The composition of any one of claims 1 to 30, wherein the composition is optionally in granular form or in the form of a gel, pastille, gum, chew, melt, tablet, lozenge, granule, or powder.

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