Oral gum composition

Abstract

The present disclosure provides a composition that is designed for oral use.The composition includes a gum base; one or more bulking agents; an active ingredient having basic amine functionality; and an organic acid, an alkali metal salt of an organic acid, or a combination thereof, wherein at least a portion of the active ingredient having basic amine functionality is bound to at least a portion of the organic acid or its alkali metal salt, and the binding 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.

Description

[Technical field]

[0001] The present disclosure relates to oral products. In particular, the present disclosure relates to compositions intended for human use. The compositions are designed for oral use and deliver substances such as flavors, active ingredients, or both during use. [Background technology]

[0002] The construction of smokeless tobacco products that combine tobacco materials, nicotine components and / or other active ingredients with a variety of binders and fillers has recently been proposed in 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. Oral products of similar formats that do not contain tobacco have also been proposed. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] US Patent Application Publication No. 2008 / 0196730 [Patent Document 2] US Patent Application Publication No. 2008 / 0305216 [Patent Document 3] US Patent Application Publication No. 2009 / 0293889 [Patent Document 4] US Patent Application Publication No. 2010 / 0291245 [Patent Document 5] US Patent Application Publication No. 2011 / 0139164 [Patent Document 6] US Patent Application Publication No. 2012 / 0037175 [Patent Document 7] US Patent Application Publication No. 2012 / 0055494 [Patent Document 8] US Patent Application Publication No. 2012 / 0138073 [Patent Document 9] US Patent Application Publication No. 2012 / 0138074 [Patent Document 10] US Patent Application Publication No. 2013 / 0074855 [Patent Document 11] US Patent Application Publication No. 2013 / 0074856 [Patent Document 12] US Patent Application Publication No. 2013 / 0152953 [Patent Document 13] US Patent Application Publication No. 2013 / 0274296 [Patent Document 14] US Patent Application Publication No. 2015 / 0068545 [Patent Document 15] US Patent Application Publication No. 2015 / 0101627 [Patent Document 16] US Patent Application Publication No. 2015 / 0230515 Summary of the Invention [Problem to be solved by the invention]

[0004] It would be desirable to provide a tobacco-free product that is constructed for oral use and that can deliver active ingredients, flavors, or both to the user in a enjoyable form. [Means for solving the problem]

[0005] The present disclosure generally provides a composition that is designed for oral use. The composition is in the form of a gum, e.g., a chewing gum. The composition comprises a gum base that comprises an elastomer that is generally insoluble in an aqueous environment (e.g., in saliva). The composition further comprises a bulking agent and an active ingredient, and may further comprise a flavoring agent, and additional components disclosed herein.

[0006] Thus, in one aspect, there is provided an oral composition comprising a gum base; one or more bulking agents; an active ingredient having basic amine functionality; and an organic acid, an alkali metal salt of an organic acid, or a combination thereof, wherein at least a portion of the active ingredient having basic amine functionality is bound to at least a portion of the organic acid or its alkali metal salt, the bond being 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.

[0007] In some embodiments, the oral composition is in the form of a chewing gum.

[0008] In some embodiments, at least a portion of the active ingredient having a basic amine functionality is in the form of an ion pair between the basic amine and the conjugate base of an organic acid.

[0009] In some embodiments, the organic acid has a logP value of about 1 to about 12. In some embodiments, the organic acid has a logP value of about 1.4 to about 4.5. In some embodiments, the organic acid has a logP value of about 2.5 to about 3.5. In some embodiments, the organic acid has a logP value of about 4.5 to about 12, and the composition further comprises a solubility enhancer. In some embodiments, the solubility enhancer is glycerol or propylene glycol.

[0010] In some embodiments, the oral 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, calculated as the amine free base, relative to the active ingredient having a basic amine functionality. In some embodiments, the oral compositions include from about 2 to about 10 molar equivalents of an organic acid, an alkali metal salt thereof, or a combination thereof, calculated as the amine free base, relative to the active ingredient having a basic amine functionality.

[0011] In some embodiments, the organic acid comprises benzoic acid, a menthyl monoester or a tocopherol monoester of a dicarboxylic acid, or a combination thereof. In some embodiments, the dicarboxylic acid is malonic acid, succinic acid, glutaric acid, adipic acid, fumaric acid, maleic acid, or a combination thereof.

[0012] In some embodiments, the organic acid comprises tocopherol succinate, monomenthyl succinate, monomenthyl fumarate, monomenthyl glutarate, or combinations thereof. In some embodiments, the oral composition further comprises benzoic acid and sodium benzoate.

[0013] In some embodiments, the oral composition comprises an organic acid and an alkali metal salt of an organic acid, in which the ratio of organic acid to alkali metal salt of an organic acid is about 0.1 to about 10.

[0014] In some embodiments, the alkali metal is sodium or potassium.

[0015] In some embodiments, the oral composition includes benzoic acid and sodium benzoate.

[0016] 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.

[0017] In some embodiments, the active ingredient having basic amine functionality is nicotine. In 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. In some embodiments, the oral composition comprises nicotine benzoate, nicotine polacrilex, or a combination thereof.

[0018] In some embodiments, the gum base comprises a synthetic elastomer, hi some embodiments, the gum base further comprises a plasticizer, a filler, a softener, an emulsifier, a wax, an anti-tack agent, an antioxidant, or a combination thereof.

[0019] In some embodiments, the bulking agent comprises one or more sugar alcohols. In some embodiments, the oral composition comprises as bulking agents a combination of sorbitol in an amount of about 25 to about 50% by weight, maltitol in an amount of about 10 to about 20% by weight, and isomalt in an amount of about 10 to about 20% by weight, each based on the total weight of the oral composition.

[0020] In some embodiments, the oral composition further comprises one or more additional active ingredients, one or more flavoring agents, one or more salts, one or more sweetening agents, one or more humectants, tobacco materials, or combinations thereof.

[0021] In some embodiments, the oral composition further comprises one or more additional active ingredients selected from the group consisting of nutraceuticals, botanicals, stimulants, amino acids, vitamins, cannabinoids, cannabis analogs, and terpenes.

[0022] In some embodiments, the oral composition comprises a gum base in an amount of about 20 to about 30% by weight, based on the total weight of the oral composition; a bulking agent in an amount of about 50 to about 80% by weight, based on the total weight of the oral composition, the bulking agent comprising one or more sugar alcohols; a humectant in an amount of about 1 to about 2% by weight, based on the total weight of the oral composition; nicotine benzoate; and sodium benzoate.

[0023] In some embodiments, the oral composition comprises a gum base in an amount of about 20 to about 30% by weight, based on the total weight of the oral composition; a bulking agent in an amount of about 50 to about 80% by weight, based on the total weight of the oral composition, the bulking agent comprising one or more sugar alcohols; a humectant in an amount of about 1 to about 2% by weight, based on the total weight of the oral composition; nicotine benzoate; nicotine polacrilex; and sodium benzoate.

[0024] In some embodiments, the oral composition comprises a gum base in an amount of about 20 to about 30% by weight, based on the total weight of the oral composition; a bulking agent in an amount of about 50 to about 80% by weight, based on the total weight of the oral composition, the bulking agent comprising one or more sugar alcohols; a humectant in an amount of about 1 to about 2% by weight, based on the total weight of the oral composition; nicotine polacrilex; and sodium benzoate.

[0025] In some embodiments, the oral composition further comprises flavor granules. In some embodiments, the flavor granules comprise a sugar alcohol in an amount of about 60 to about 90% by weight; a humectant in an amount of about 16 to about 22% by weight; a sweetener in an amount of about 0.1 to about 0.5% by weight; a filler in an amount of about 1 to about 3% by weight; a colorant; and a flavoring agent (each amount by weight based on the total weight of the flavor granules). In some embodiments, the sugar alcohol is isomalt, the humectant is glycerin, the sweetener is sucralose, and the filler is microcrystalline cellulose.

[0026] In some embodiments, the flavor granules comprise a sugar alcohol in an amount of about 15 to about 35% by weight, a humectant in an amount of about 15 to about 30% by weight, a sweetener in an amount of about 0.1 to about 0.5% by weight, a filler in an amount of about 20 to about 50% by weight, a flavoring agent in an amount of about 20 to about 30% by weight, and a colorant, each amount by weight being based on the total weight of the flavor granules. In some embodiments, the sugar alcohol is isomalt, the humectant is glycerin, the sweetener is sucralose, and the filler is microcrystalline cellulose.

[0027] In some embodiments, the flavor granules comprise a combination of two sugar alcohols in a total amount of about 96 to about 99% by weight, a sweetener in an amount of about 0.1 to about 0.5% by weight, a flavoring agent in an amount of about 0.1 to about 1% by weight, and a coloring agent in an amount of about 0.1 to about 1.5% by weight (each amount by weight is based on the total weight of the flavor granules). In some embodiments, the flavor granules comprise isomalt in an amount of about 92 to about 96% by weight, maltitol syrup in an amount of about 4 to about 6% by weight, sucralose in an amount of about 0.1 to about 0.5% by weight, and the remainder comprises coloring agents and flavoring agents.

[0028] The present disclosure includes, but is not limited to, the following embodiments.

[0029] Embodiment 1: An oral composition comprising a gum base; one or more bulking agents; an active ingredient having basic amine functionality; and an organic acid, an alkali metal salt of an organic acid, or a combination thereof, wherein at least a portion of the active ingredient having basic amine functionality is bound to at least a portion of the organic acid or its alkali metal salt, said bond being 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.

[0030] Embodiment 2: The oral composition of embodiment 1 in the form of a chewing gum.

[0031] Embodiment 3: The oral composition of embodiment 1 or 2, wherein at least a portion of the active ingredient having a basic amine functionality is in the form of an ion pair between a basic amine and a conjugate base of an organic acid.

[0032] Embodiment 4: The oral composition of any one of embodiments 1-3, wherein the organic acid has a logP value of from about 1 to about 12.

[0033] Embodiment 5: The oral composition of any one of embodiments 1 to 4, wherein the organic acid has a logP value of from about 1.4 to about 4.5.

[0034] Embodiment 6: The oral composition of any one of embodiments 1 to 5, wherein the organic acid has a logP value of about 2.5 to about 3.5.

[0035] Embodiment 7: The oral composition of any one of embodiments 1-6, wherein the organic acid has a logP value of about 4.5 to about 12, and the composition further comprises a solubility enhancer.

[0036] Embodiment 8: The oral composition of embodiment 7, wherein the solubility enhancer is glycerol or propylene glycol.

[0037] Embodiment 9: The oral composition of any one of embodiments 1 to 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 active ingredient having a basic amine functionality, calculated as the amine free base.

[0038] Embodiment 10: The oral 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, calculated as the amine free base, relative to the active ingredient having a basic amine functionality.

[0039] Embodiment 11: The oral composition of any one of embodiments 1-10, wherein the organic acid comprises benzoic acid, a menthyl monoester of a dicarboxylic acid, or a tocopherol monoester, or a combination thereof.

[0040] Embodiment 12: The oral composition of any one of embodiments 1-11, wherein the dicarboxylic acid is malonic acid, succinic acid, glutaric acid, adipic acid, fumaric acid, maleic acid, or a combination thereof.

[0041] Embodiment 13: The oral composition of any one of embodiments 1-12, wherein the organic acid is tocopherol succinate, monomenthyl succinate, monomenthyl fumarate, monomenthyl glutarate, or combinations thereof.

[0042] Embodiment 14: The oral composition of any one of embodiments 1-13, further comprising benzoic acid and sodium benzoate.

[0043] Embodiment 15: The oral composition of any one of embodiments 1-14, comprising benzoic acid and sodium benzoate.

[0044] Embodiment 16: The oral composition of any one of embodiments 1-15, comprising an organic acid and an alkali metal salt of an organic acid.

[0045] Embodiment 17: The oral composition of any one of embodiments 1-16, wherein the alkali metal is sodium or potassium.

[0046] Embodiment 18: The oral composition of any one of embodiments 1-17, wherein the ratio of organic acid to alkali metal salt of the organic acid is from about 0.1 to about 10.

[0047] Embodiment 19: The oral composition of any one of embodiments 1 to 18, wherein the pH of the composition is from about 4.0 to about 9.0.

[0048] Embodiment 20: The oral composition of any one of embodiments 1 to 19, wherein the pH of the composition is from about 4.5 to about 7.

[0049] Embodiment 21: The oral composition of any one of embodiments 1 to 20, wherein the pH of the composition is from about 5.5 to about 7.

[0050] Embodiment 22: The oral composition of any one of embodiments 1 to 21, wherein the pH of the composition is from about 4.0 to about 5.5.

[0051] Embodiment 23: The oral composition of any one of embodiments 1 to 22, wherein the pH of the composition is from about 7.0 to about 9.0.

[0052] Embodiment 24: The oral composition of any one of embodiments 1 to 23, wherein the active ingredient having basic amine functionality is nicotine.

[0053] Embodiment 25: The oral composition of any one of embodiments 1 to 24, wherein 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.

[0054] Embodiment 26: The oral composition of any one of embodiments 1-25, comprising a nicotine salt (e.g., nicotine benzoate), nicotine polacrilex, or a combination thereof.

[0055] Embodiment 27: The oral composition of any one of embodiments 1 to 26, wherein the gum base comprises a synthetic elastomer.

[0056] Embodiment 28: The oral composition of any one of embodiments 1-27, wherein the gum base further comprises a plasticizer, a filler, a softener, an emulsifier, a wax, an anti-tack agent, an antioxidant, or a combination thereof.

[0057] Embodiment 29: The oral composition of any one of embodiments 1 to 28, wherein the bulking agent comprises one or more sugar alcohols.

[0058] Embodiment 30: The oral composition of any one of embodiments 1 to 29, comprising as a bulking agent a combination of sorbitol in an amount of about 25 to about 50% by weight, maltitol in an amount of about 10 to about 20% by weight, and isomalt in an amount of about 10 to about 20% by weight (each based on the total weight of the oral composition).

[0059] Embodiment 31: The oral composition of any one of embodiments 1 to 30, further comprising one or more additional active ingredients, one or more flavoring agents, one or more salts, one or more sweetening agents, one or more humectants, tobacco materials, or combinations thereof.

[0060] Embodiment 32: The oral composition of any one of embodiments 1 to 31, further comprising one or more additional active ingredients selected from the group consisting of nutraceuticals, botanicals, stimulants, amino acids, vitamins, cannabinoids, cannabis analogs and terpenes.

[0061] Embodiment 33: The oral composition of any one of embodiments 1 to 32, comprising: a gum base in an amount of about 20 to about 30% by weight, based on the total weight of the oral composition; a bulking agent in an amount of about 50 to about 80% by weight, based on the total weight of the oral composition, the bulking agent comprising one or more sugar alcohols; a humectant in an amount of about 1 to about 2% by weight, based on the total weight of the oral composition; nicotine benzoate; and sodium benzoate (or other alkali metal benzoate).

[0062] Embodiment 34: An oral composition comprising a gum base; one or more bulking agents; an active ingredient having basic amine functionality; and an organic acid, wherein the organic acid comprises a menthyl monoester or a tocopherol monoester of a dicarboxylic acid, such as a dicarboxylic acid selected from benzoic acid, malonic acid, succinic acid, glutaric acid, adipic acid, fumaric acid, maleic acid, or combinations thereof, or combinations thereof, in particular the organic acid comprises tocopherol succinate, monomenthyl succinate, monomenthyl fumarate, monomenthyl glutarate, or combinations thereof.

[0063] Embodiment 35: The oral composition of embodiment 34, wherein the active ingredient having basic amine functionality is nicotine.

[0064] Embodiment 36: The oral composition of embodiment 35, wherein the nicotine comprises a nicotine salt, nicotine polacrilex, or a combination thereof.

[0065] Embodiment 37: The oral composition of any one of embodiments 34-36, comprising nicotine benzoate.

[0066] Embodiment 38: The oral composition of any one of embodiments 34 to 37, comprising nicotine polacrilex.

[0067] Embodiment 39: The oral composition of any one of embodiments 34-38, comprising a combination of nicotine benzoate and nicotine polacrilex.

[0068] Embodiment 40: The oral composition of claim 1, comprising: a gum base in an amount of about 20 to about 30% by weight, based on the total weight of the oral composition; a bulking agent in an amount of about 50 to about 80% by weight, based on the total weight of the oral composition, the bulking agent comprising one or more sugar alcohols; a humectant in an amount of about 1 to about 2% by weight, based on the total weight of the oral composition; nicotine polacrilex; and sodium benzoate.

[0069] Embodiment 41: The oral composition of any one of embodiments 1 to 40, further comprising flavor granules.

[0070] Embodiment 42: The oral composition of embodiment 41, wherein the flavor granules comprise: a sugar alcohol in an amount of about 60 to about 90% by weight; a humectant in an amount of about 16 to about 22% by weight; a sweetener in an amount of about 0.1 to about 0.5% by weight; a filler in an amount of about 1 to about 3% by weight; a colorant; and a flavoring agent (each amount by weight based on the total weight of the flavor granules).

[0071] Embodiment 43: The oral composition of embodiment 42, wherein the sugar alcohol is isomalt, the humectant is glycerin, the sweetener is sucralose, and the filler is microcrystalline cellulose.

[0072] Embodiment 44: The oral composition of embodiment 41, wherein the flavor granules comprise: a sugar alcohol in an amount of about 15 to about 35% by weight; a humectant in an amount of about 15 to about 30% by weight; a sweetener in an amount of about 0.1 to about 0.5% by weight; a filler in an amount of about 20 to about 50% by weight; a flavoring agent in an amount of about 20 to about 30% by weight; and a colorant (each amount by weight based on the total weight of the flavor granules).

[0073] Embodiment 45: The oral composition of embodiment 44, wherein the sugar alcohol is isomalt, the humectant is glycerin, the sweetener is sucralose, and the filler is microcrystalline cellulose.

[0074] Embodiment 46: The oral composition of embodiment 41, wherein the flavor granules comprise a combination of two sugar alcohols in a total amount of about 96 to about 99% by weight; a sweetener in an amount of about 0.1 to about 0.5% by weight; a flavoring agent in an amount of about 0.1 to about 1% by weight; and a colorant in an amount of about 0.1 to about 1.5% by weight (each amount by weight based on the total weight of the flavor granules).

[0075] Embodiment 47: The oral composition of embodiment 46, wherein the granules comprise isomalt in an amount of about 92 to about 96% by weight; maltitol syrup in an amount of about 4 to about 6% by weight; sucralose in an amount of about 0.1 to about 0.5% by weight, with the remainder consisting of colorants and flavoring agents.

[0076] These and other features, aspects and advantages of the present disclosure will become apparent upon reading the following detailed description. 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. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0077] The present disclosure will now be described more fully hereinafter with reference to the exemplary embodiments. 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.

[0078] As used in this specification and the claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0079] The term "about" is used throughout this specification to describe and take into account slight variations. For example, the term "about" can refer to ±10% or less, such as ±5% or less, ±2% or less, ±1% or less, ±0.5% or less, ±0.2% or less, ±0.1% or less, or ±0.05% or less. All numerical values ​​are modified herein by the term "about", whether or not expressly indicated. Values ​​modified by the term "about" are, of course, inclusive of the specified value. For example, "about 5.0" must include 5.0.

[0080] 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 composition including water. Unless otherwise indicated, references to the "weight percent" of a composition reflect the total wet weight of the composition (i.e., including water).

[0081] Oral composition As described herein, an oral composition is provided that includes a gum base; one or more bulking agents; an active ingredient with basic amine functionality; and an organic acid, an alkali metal salt of an organic acid, or a combination thereof. The oral composition may further include additional active ingredients, flavoring agents, salts, sweeteners, humectants, tobacco materials, or a combination thereof. The relative amounts of various components in the composition may vary and are typically selected to provide the oral composition with desired sensory and performance characteristics. Exemplary individual components of the oral composition and characteristics of the oral composition are described herein below.

[0082] Gum base The oral compositions disclosed herein include a gum base. The term "gum base" generally refers to a water-insoluble and hydrophobic component that provides the oral composition with a desired texture. The oral composition may include gum base in an amount of about 5 to about 95 percent by weight based on the total weight of the oral composition, such as about 5, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, or about 50 to about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, or about 95 percent by weight based on the total weight of the oral composition. In some embodiments, the oral composition may include gum base in an amount of about 10 to about 60 percent by weight, such as about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, or about 60 percent by weight based on the total weight of the oral composition. In some embodiments, the oral composition comprises a gum base in an amount of about 15 to about 40 or about 20 to about 30 weight percent based on the total weight of the oral composition.

[0083] The formulation of the gum base can vary substantially depending on the particular oral composition being prepared and the desired chewability and other sensory characteristics of the final oral composition (e.g., hardness and elasticity, as well as a number of subjective parameters related to the chewiness experienced by the user). Generally, the gum base comprises an elastomer. The elastomer provides a rubbery, tacky quality to the gum base and the overall oral composition. This rubbery, tacky quality can vary depending on the chemical structure of the elastomer and how it is compounded with other ingredients in the gum base and the overall oral composition. Thus, the elastomer used in the gum base can vary depending on a variety of factors such as the type of gum base desired, the desired texture of the gum, and the other components used to make the final oral composition. Generally, the elastomer can be any water-insoluble polymer known in the art. Elastomers suitable for use in the gum base of the present invention can include natural, synthetic, or combinations thereof.

[0084] In some embodiments, the elastomer is a natural elastomer. Non-limiting examples of suitable natural elastomers include latex, chicle, crown gum, nispero, rosidinha, jelutong, perillo, Niger gutta, tunu, balata, gutta percha, reticaspi, sorba, gutta kei, masaranduba balata, masaranduba chocolate, nispero, rosindinha, gutta hankan, chiquibul, pendare, leche de vaca, tunu, chilte, and mixtures thereof.

[0085] In some embodiments, the elastomer is a synthetic elastomer. Non-limiting examples of suitable synthetic elastomers include styrene-butadiene copolymer (SBR), polyisobutylene, isobutylene-isoprene copolymer, polyethylene, polyvinyl acetate, biodegradable polymers, and mixtures thereof. Further examples of synthetic elastomers include, but are not limited to, synthetic elastomers listed in the Food and Drug Administration, CFR, Title 21, Section 172,615, the Masticatory Substances, Synthetic. In some embodiments, the synthetic elastomer is biodegradable, for example, a lactic acid polymer. In some embodiments, the synthetic elastomer is a polyisobutylene having a gel permeation chromatography (GPC) average molecular weight ranging from about 10,000 to 1,000,000, such as about 50,000 to 80,000. In some embodiments, the synthetic elastomer is an isobutylene-isoprene copolymer, a styrene-butadiene copolymer (e.g., having a styrene-butadiene ratio of about 1:3 to 3:1) or a polyvinyl acetate (PVA) polymer. Suitable isobutylene-isoprene copolymers, styrene-butadiene copolymers and polyvinyl acetate polymers can have a GPC average molecular weight ranging from about 2,000 to 90,000, such as from about 3,000 to about 80,000 or from about 30,000 to about 50,000.

[0086] In some embodiments, synthetic elastomers having high molecular weight and synthetic elastomers having low molecular weight are combined. Examples of such combinations are polyisobutylene and styrene-butadiene copolymers, polyisobutylene and polyisoprene copolymers, polyisobutylene and isobutylene-isoprene copolymers, and combinations thereof. Any of the above individual synthetic polymers may further include polyvinyl acetate, vinyl acetate-vinyl laurate copolymers, biodegradable polymers, and mixtures thereof.

[0087] Gum bases, particularly those based on synthetic elastomers, may further comprise one or more of the following: plasticizers, fillers, softeners, emulsifiers, waxes, anti-tackifiers, and more miscellaneous components such as antioxidants, colorants, flavors, buffers, and the like.

[0088] In some embodiments, the gum base includes a plasticizer. Plasticizers disrupt intermolecular polymer chains to various degrees, thus altering the elasticity and flexibility of the gum base. Suitable plasticizers include natural resins, synthetic resins, waxes, and combinations thereof. Natural resins include, but are not limited to, natural terpene resins, and natural rosin esters, often referred to as ester gums. Non-limiting examples of natural rosin esters include glycerol esters of partially hydrogenated rosin, glycerol esters of polymerized rosin, glycerol esters of partially dimerized rosin, glycerol esters of tall oil rosin, pentaerythritol esters of partially hydrogenated rosin, methyl esters of rosin, partially hydrogenated methyl esters of rosin, and pentaerythritol esters of rosin. Synthetic resins include, but are not limited to, terpene resins derived from alpha-pinene, beta-pinene, and / or d-limonene.

[0089] In some embodiments, the gum base comprises a wax. Examples of suitable waxes include, but are not limited to, microcrystalline wax, rice wax, carnauba wax, beeswax, rice bran wax, and candelilla wax.

[0090] In some embodiments, the gum base comprises a filler. Suitable fillers include, but are not limited to, magnesium carbonate, calcium carbonate, ground limestone, silicates (such as magnesium silicate and aluminum silicate), clay, alumina, talc, titanium dioxide, monocalcium phosphate, dicalcium phosphate and tricalcium phosphate, cellulose polymers and combinations thereof. In a particular embodiment, the filler is calcium carbonate, talc or a combination thereof. In one particular embodiment, the filler is talc.

[0091] In some embodiments, the gum base comprises an emulsifier. Certain emulsifiers may further act as softeners. Suitable emulsifiers and / or softeners include, but are not limited to, tallow, hydrogenated tallow, hydrogenated and partially hydrogenated vegetable oils, cocoa butter, glycerol monostearate, glycerol acetate, glycerol diacetate (diacetin), glycerol triacetate (triacetin), lecithin, monoglycerides, diglycerides and triglycerides, acetylated monoglycerides, fatty acids (e.g., stearic acid, palmitic acid, oleic acid and linoleic acid), sorbitan fatty acid esters, lanolin and combinations thereof.

[0092] In some embodiments, the gum base comprises an antioxidant. Examples of suitable antioxidants include, but are not limited to, butylated hydroxyanisole (BHA), butylated hydroxy-toluene (BHT), tertiary butylhydroquinone (TBHQ), tocopherol, mixed tocopherols, eugenol, guaiac butter, thymol, carvacrol, spice extracts of thyme, oregano, rosemary, nutmeg, ginger, and mixtures thereof.

[0093] The amount of each of the individual components of the gum base may vary. Typical ranges of the above-mentioned gum base components, expressed as percent by weight, based on the total weight of the gum base, are about 5 to about 80% elastomer; about 1 to about 80% plasticizer; about 0 to about 40% wax; about 0 to about 35% emulsifier / softener; about 0 to about 50% filler; and about 0 to 5% other miscellaneous ingredients (antioxidants, colorants, etc.).

[0094] In some embodiments, the gum base comprises a mixture of elastomeric polymers, resins, refined waxes, glycerol esters of edible fatty acids, talc, and antioxidants, each as described herein above. One particularly suitable example of such a gum base is available as Artica T, available from CAFOSA Gum S / A (Barcelona, ​​Spain).

[0095] Bulking Agent The oral compositions disclosed herein include one or more bulking agents. Such bulking agents are generally at least partially water-soluble, and may be completely water-soluble. Bulking agents may serve more than one purpose. For example, bulking agents can act as fillers (i.e., providing physical bulk to the composition), as sweeteners, and as texture modifiers (e.g., contributing physical attributes such as chewiness, elasticity, softness, etc.). Suitable bulking agents include sweeteners such as sugars, sugar alcohols, and combinations thereof. Sugars generally include sugar-containing components (e.g., monosaccharides and disaccharides or polysaccharides). Suitable sugars include, but are not limited to, glucose, sucrose, dextrose, lactose, maltose, isomaltulose, dry invert sugar, fructose, levulose, galactose, corn syrup solids, hy-maltose syrup, invert / isomerized fructose syrup, maltotriose, erythrose, xylose, leucrose, mannose, and L-sugar. Sugar alcohols are polyols derived from monosaccharides or disaccharides, having a partially or fully hydrogenated form (e.g., hydrogenated starch hydrolysates). Sugar alcohols have, for example, about 4 to about 20 carbon atoms and include erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, and sorbitol.

[0096] In some embodiments, the bulking agent comprises one or more sugar alcohols. In some embodiments, the one or more sugar alcohols are selected from the group consisting of erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and combinations thereof. In some embodiments, the one or more sugar alcohols are selected from the group consisting of isomalt, maltitol, mannitol, sorbitol, and combinations thereof. In certain embodiments, the bulking agent is a combination of sorbitol, maltitol, and isomalt. Isomalt is an equimolar mixture of two disaccharides, each consisting of the following two sugars: glucose and mannitol (α-D-glucopyranoside-1,6-mannitol); and glucose and sorbitol (α-D-glucopyranoside-1,6-sorbitol). In some embodiments, the isomalt is in crystalline form. Crystalline isomalt is commercially available or can be prepared from isomalt by heating (eg, to a temperature above about 130° C., or above about 160° C.) prior to crystallization by known methods.

[0097] The amount of bulking agent may vary depending on the gum base and amount thereof used, as well as the desired chewiness, sweetness, etc. In general, the oral composition comprises bulking agent in an amount of about 5 to about 95% by weight, such as about 10 to about 90%, about 30 to about 90%, or about 40 to about 90% by weight of the oral composition, based on the total weight of the oral composition. In certain embodiments, the oral composition comprises sorbitol in an amount of about 25 to about 50% by weight, maltitol in an amount of about 10 to about 20% by weight, and isomalt in an amount of about 10 to about 20% by weight, based on the total weight of the oral composition.

[0098] active ingredient The oral compositions disclosed herein 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 effect 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 effects in the diagnosis, cure, mitigation, treatment, or prevention of disease, or that affect the structure or any function of the human body (e.g., provide a stimulating effect on the central nervous system, have an energizing 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, nutraceutical, "phytochemical agent," or "functional food." These types of additives may also be defined in the art to include substances that provide one or more beneficial biological effects (e.g., health promotion, disease prevention, or other pharmacological effects), but are not classified or regulated as drugs, and are normally available from naturally derived sources (e.g., botanical materials).

[0099] Non-limiting examples of active ingredients include those falling into the categories of botanical ingredients, stimulants, amino acids, nicotine ingredients, 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 the particular oral product.

[0100] The specific percentage of active ingredients present will vary depending on the desired characteristics of the particular oral product. Typically, the active ingredient or combinations thereof will be 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 combinations of active ingredients will be 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.

[0101] Nicotine content In certain embodiments, the active ingredient comprises a nicotine component. By "nicotine component" is meant any suitable form of nicotine (e.g., free base or salt) to provide oral absorption of at least a portion of the nicotine present. 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., synthetic or otherwise obtained). Most preferably, the nicotine is natural and is obtained as an extract from Nicotiana species (e.g., tobacco). The nicotine may have the enantiomeric form S(-)-nicotine, R(+)-nicotine, or a mixture of S(-)-nicotine and R(+)-nicotine. Most preferably, the nicotine is in the form of S(-)-nicotine (e.g., a form that is substantially all S(-)-nicotine) or a racemic mixture composed primarily or predominantly of S(-)-nicotine (e.g., a mixture composed of about 95 parts by weight of S(-)-nicotine and about 5 parts by weight of R(+)-nicotine). Most preferably, the nicotine is utilized in a substantially pure form or in an essentially pure form. Highly preferred nicotine utilized has a purity of greater than about 95 percent, more preferably greater than about 98 percent, and most preferably greater than about 99 percent, on a weight basis.

[0102] Typically, the nicotine component is selected from the group consisting of nicotine free base and nicotine salt.In some embodiments, the nicotine component is nicotine in free base form, which can be easily adsorbed, for example, on microcrystalline cellulose material to form microcrystalline cellulose-nicotine carrier complex.See, for example, the discussion of nicotine in free base form in Hansson's US Patent Application No. 2004 / 0191322, which is incorporated herein by reference.

[0103] In some embodiments, at least a portion of the nicotine component can be utilized in the form of a salt. The nicotine salt can be provided using the types of ingredients and techniques described in U.S. Patent No. 2,033,909 to Cox et al. and Perfetti, Beitrage Tabakforschung Int., vol. 12:43-54 (1983), which are incorporated herein by reference. Additionally, salts of nicotine are available from sources such as, for example, Pfaltz and Bauer, Inc. and K&K Laboratories, Division of ICN Biochemicals, Inc. Typically, the nicotine component is selected from the group consisting of nicotine free base, nicotine salts, such as hydrochloride, dihydrochloride, monotartrate, bitartrate, sulfate, salicylate, and zinc nicotine chloride. In some embodiments, the nicotine component is nicotine bitartrate.

[0104] In some embodiments, at least a portion of the nicotine can be in the form of a resin complex of nicotine, where the nicotine is bound to an ion exchange resin, such as nicotine polacrilex, which is, for example, nicotine bound to polymethacrylic acid, such as Amberlite IRP64, Purolite C115HMR, or Doshion P551. See, for example, U.S. Patent No. 3,901,248 to Lichtneckert et al., which is incorporated herein by reference. Another example is a nicotine-polyacryl carbomer complex, such as Carbopol 974P. In some embodiments, the nicotine can be present in the form of a nicotine polyacryl complex.

[0105] In some embodiments, at least a portion of the nicotine component may form an ion pair, as further described herein below.

[0106] Typically, the nicotine component (calculated as the free base), if present, 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 is present in a concentration of about 0.1% w / w to about 10% by weight, such as, 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 wt%, 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%, calculated as the free base based on the total weight of the composition. In some embodiments, the nicotine component is present in a concentration of 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, for example, about 0.1% w / w to about 2.5% by weight, about 0.1% by weight to about 2.0% by weight, about 0.1% by weight to about 1.5% by weight, or about 0.1% by weight to about 1% by weight. The total amount of nicotine present may be provided by more than one nicotine source, such as any of various combinations of nicotine free base, nicotine salts, ion-paired nicotine, and polymer-bound nicotine (e.g., nicotine polacrilex). In some embodiments, the nicotine component is nicotine benzoate, nicotine polacrilex, or mixtures thereof.

[0107] In some embodiments, the oral products or compositions of the present disclosure can be characterized as being completely free or substantially free of any nicotine components (e.g., any embodiment disclosed herein can be completely or substantially free of any nicotine components). By "substantially free" we mean that no nicotine has been intentionally added beyond trace amounts that may be naturally present in, for example, botanical materials. For example, certain embodiments can be characterized as having less than 0.001% nicotine by weight, calculated as the free base, or less than 0.0001% nicotine by weight, or even less than 0% nicotine by weight.

[0108] 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 purposes of this disclosure, "botanical" includes, but is not limited to, "herbal materials," which refer to seed-producing plants that do not produce persistent woody tissue and are often valued for their medicinal or sensory properties (e.g., tea or herbal tea). When referring to "non-tobacco" botanical materials, tobacco materials are intended to be excluded (i.e., not including any Nicotiana species). The botanical materials used in the present invention can include any of the compounds and sources described herein, including, but not limited to, mixtures thereof. Certain botanical materials of this type are sometimes called dietary supplements, nutraceuticals, "phytochemicals" or "functional foods."

[0109] If present, the botanicals will typically be at a concentration of about 0.01 w / w% to about 10 wt%, 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 wt%, 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%, about 11 wt%, about 12 wt%, about 13 wt%, about 14 wt%, or about 15 wt%, based on the total weight of the composition.

[0110] 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, nutraceuticals, "phytochemical agents" or "functional foods." Certain botanicals find use in traditional herbal medicines as botanical materials or botanical extracts, and are further described herein.

[0111] 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.

[0112] Stimulants In some embodiments, the active ingredient comprises one or more stimulants. As used herein, the term "stimulant" refers to a material that increases the activity of the central nervous system and / or the body, for example, enhancing focus, cognition, energy, mood, alertness, etc. Non-limiting examples of stimulants include caffeine, theacrine, theobromine, and theophylline. Theacrine (1,3,7,9-tetramethyluric acid) is a purine alkaloid structurally related to caffeine and has stimulating, analgesic, and anti-inflammatory properties. Stimulants present may be natural, derived from nature, or completely synthetic. For example, certain botanical materials (such as guarana, tea, coffee, cocoa, etc.) may have stimulant properties due to the presence of, for example, caffeine or related alkaloids, and are therefore "natural" stimulants. "Naturally derived" means that the stimulant (e.g., caffeine, theacrine) is in a purified form outside of its natural (e.g., botanical) matrix. For example, caffeine can be obtained by extraction and purification from botanical sources (e.g., tea). "Fully synthetic" means that the stimulant is obtained by chemical synthesis. In some embodiments, the active ingredient 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.

[0113] 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.

[0114] amino acid In some embodiments, the active ingredient comprises an amino acid. As used herein, the term "amino acid" refers to an amine (-NH 2 ) and carboxyl (-COOH) or sulfonic acid (SO 3 H) functional group along with a side chain (R group) that is specific for each amino acid. Amino acids may be proteinogenic or non-proteinogenic. "Proteogenic" means that the amino acid is one of the 20 naturally occurring amino acids found in proteins. Proteinogenic amino acids include alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. "Non-proteinogenic" means that the amino acid is not naturally found in proteins or produced directly by cellular machinery (e.g., is a product of post-translational modification). Non-limiting examples of non-proteinogenic amino acids include gamma-aminobutyric acid (GABA), taurine (2-aminoethanesulfonic acid), theanine (L-gamma-glutamylethylamide), hydroxyproline, and beta-alanine.

[0115] 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%, up 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.

[0116] 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.

[0117] 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.

[0118] 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.

[0119] 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.

[0120] 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).

[0121] 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.

[0122] 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 this 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.

[0123] 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.

[0124] 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.

[0125] 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.

[0126] 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.

[0127] 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 are represented by the general formula: 5 H 8 ) nTerpenes are believed to have the formula: and include monoterpenes, sesquiterpenes, and diterpenes. Terpenes can be acyclic, monocyclic, or bicyclic structures. Some terpenes provide an entourage effect when used in combination with cannabinoids or cannabis analogues. Examples include beta-caryophyllene, linalool, limonene, beta-citronellol, linalyl acetate, pinene (alpha or beta), geraniol, carvone, eucalyptol, menthone, iso-menthone, piperitone, myrcene, beta-bourbonene, and germacrene, which can be used individually or in combination.

[0128] 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.

[0129] 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.

[0130] Examples of botanical ingredients with antioxidant properties include, without limitation, acai berry, alfalfa, allspice, annatto seed, apricot oil, basil, bee balm, wild bergamot, black pepper, blueberry, borage seed oil, burdock, cacao, calamus root, catnip, catuaba, cayenne pepper, chaga mushroom, chervil, cinnamon, dark chocolate, potato skin, grape seed, carrot, ginkgo biloba, St. John's wort, saw palmetto, green tea, black tea, black cohosh, cayenne, chamomile, cloves, cocoa powder, cranberry, dandelion, grapefruit, honeybush, echinacea, garlic, evening primrose, feverfew, ginger, goldenseal, hawthorn, and hibiscus. flowers, gynostemma, kava, lavender, licorice, origanum, milk thistle, mint, oolong tea, beet root, orange, oregano, papaya, pennyroyal, peppermint, red clover, rooibos (red or green), rose hips, rosemary, sage, clary sage, savory, spearmint, spirulina, slippery elm bark, sorghum bran high tannin, sorghum seed high tannin, sumac bran, comfrey leaf and root, goji berry, gotu kola, thyme, turmeric, uva ursi, valerian, wild yam root, wintergreen, yacon root, yellow dock, yerba mate, yerba santa, bacopa monniera, ashwagandha, yamabushitake and silybum marianum. Such botanical materials may be provided in fresh or dried form, in essential oils, or in the form of extracts. Botanical materials (as well as their extracts) often contain various classes of compounds known to provide antioxidant benefits, such as minerals, vitamins, isoflavones, phytosterols, allyl sulfides, dithiolthiones, isothiocyanates, indoles, lignans, flavonoids, polyphenols, and carotenoids.Examples of compounds found in botanical extracts or oils include ascorbic acid, peanut endocarp, resveratrol, sulforaphane, β-carotene, lycopene, lutein, coenzyme Q, carnitine, quercetin, kaempferol, etc. See, e.g., Santhosh et al., Phytomedicine, 12 (2005) pp. 216-220, incorporated herein by reference.

[0131] 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.

[0132] 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.

[0133] Pharmaceutical Ingredients In some embodiments, the active ingredient comprises an active pharmaceutical ingredient (API). APIs can be any known pharmaceutical agent adapted for therapeutic, prophylactic or diagnostic use. These can include, for example, synthetic organic compounds, proteins and peptides, polysaccharides and other sugars, lipids, phospholipids, inorganic compounds (e.g., magnesium, selenium, zinc, nitrates), neurotransmitters or their precursors (e.g., serotonin, 5-hydroxytryptophan, oxytriptan, acetylcholine, dopamine, melatonin) and nucleic acid sequences, which have therapeutic, prophylactic or diagnostic activity. Non-limiting examples of APIs include analgesics and antipyretics (e.g., acetylsalicylic acid, acetaminophen, 3-(4-isobutylphenyl)propanoic acid), phosphatidylserine, myo-inositol, docosahexaenoic acid (DHA, omega-3), arachidonic acid (AA, omega-6), S-adenosylmethionine (SAM), beta-hydroxy-beta-methylbutyrate (HMB), citicoline (cytidine-5'-diphosphate-choline), and cotinine. In some embodiments, the active ingredient includes citicoline. In some embodiments, the active ingredient is a combination of citicoline, caffeine, theanine, and carrot. In some embodiments, the active ingredient includes sunflower lecithin. In some embodiments, the active ingredient is a combination of sunflower lecithin, caffeine, theanine, and carrot.

[0134] The amount of API may vary. For example, when present, the API is typically present in an amount of from about 0.001% w / w to about 10% 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%.

[0135] Bleached active ingredients In some embodiments, the composition comprises an active ingredient disclosed herein, characterized in that the active ingredient is bleached. Such a bleached active ingredient may be desirable, for example, to prevent tooth discoloration during use of the composition, or so that any residue remaining in the user's mouth after use of the product is not visible and is unlikely to cause staining of textile materials, such as clothing, that may come into contact with the residue. By "bleached" active ingredient is meant an active ingredient (e.g., a botanical material or a derivative thereof) that is colored in its natural state and has been treated to reduce or eliminate the color. By "color" is meant a characterization of human vision, described by a classification of colors by names such as red, blue, yellow (primary colors), or brown, orange, green, purple, etc., derived from combinations of the primary colors. Such a sense of color is derived from the stimulation of cone cells in the human eye by electromagnetic radiation in the visible spectrum associated with an object, depending on the wavelength of light reflected from the object. This reflection is governed by the physical properties of the object, such as, for example, the absorption and emission spectrum of the entire electromagnetic spectrum.

[0136] Certain active ingredients impart color to the active ingredient due to naturally occurring chemical compounds therein that reflect light in the visible range of the electromagnetic spectrum (e.g., chlorophyll or pigment breakdown products in certain botanical materials that cause green and brown colors, respectively). Such chemical compounds, or portions thereof, that cause the color of the active ingredient may be chemically modified or removed by various treatments. In some embodiments, the treatment is effective to remove at least 70% of the chemicals present in the active ingredient that have a maximum transmittance of wavelengths in the visible range of the electromagnetic spectrum, relative to the weight of the naturally occurring compounds. For example, such treatments may be effective to remove 70%, 80%, 90%, 95%, 99%, or even 100% of the naturally occurring compounds that cause the visible color of the active ingredient.

[0137] In some embodiments, the treatment for bleaching (i.e., modification or removal of color-causing chemical compounds from the active ingredients) includes extraction, chemical bleaching, or a combination thereof. One particularly suitable extraction method is extraction with supercritical carbon dioxide (CO 2 ) extraction. Chemical bleaching methods for botanical materials, including tobacco, are known and include, by way of non-limiting example, treatment with hydrogen peroxide, ozone, or other oxidizing agents. For example, bleached active ingredients (e.g., bleached botanical materials or tobacco materials) may be produced by a variety of whitening methods using a variety of bleaching or oxidizing agents. Exemplary oxidizing agents include peroxides (e.g., hydrogen peroxide), chlorites, chlorates, perchlorates, hypochlorites, ozone, ammonia, potassium permanganate, and combinations thereof. An oxidation catalyst may be used. Exemplary oxidation catalysts are titanium dioxide, manganese dioxide, and combinations thereof.

[0138] Bleaching methods known for bleaching tobacco may be applied to the present active ingredients. Processes for treating tobacco with bleaching agents are described, for example, in U.S. Patent No. 787,611 to Daniels, Jr.; U.S. Patent No. 1,086,306 to Oelenheinz; U.S. Patent No. 1,437,095 to Delling; U.S. Patent No. 1,757,477 to Rosenhoch; U.S. Patent No. 2,122,421 to Hawkinson; U.S. Patent No. 2,148,147 to Baier; U.S. Patent No. 2,170,107 to Baier; U.S. Patent No. 2,274,649 to Baier; U.S. Patent No. 2,770,239 to Pratz et al.; U.S. Patent No. 2,274,649 to Pratz et al.; U.S. Patent No. 2,3 ...274,649 to Pratz et al.; U.S. Patent No. 2,274,649 to Pratz et al.; U.S. Patent No. 2,274 No. 3,612,065 to Rosen; U.S. Patent No. 3,851,653 to Rosen; U.S. Patent No. 3,889,689 to Rosen; U.S. Patent No. 3,943,940 to Minami; U.S. Patent No. 3,943,945 to Rosen; U.S. Patent No. 4,143,666 to Rainer; U.S. Patent No. 4,194,514 to Campbell; U.S. Patent Nos. 4,366,823, 4,366,824, and 4,388,933 to Rainer et al.; U.S. Patent No. 4,641,667 to Schmekel et al.; U.S. Patent No. 5,713,376 to Berger; Byrd No. 9,339,058 to Byrd Jr. et al.; U.S. Pat. No. 9,420,825 to Beeson et al.; and U.S. Pat. No. 9,950,858 to Byrd Jr. et al.; as well as U.S. Patent Application Publication No. 2012 / 0067361 to Bjorkholm et al.; U.S. Patent Application Publication No. 2016 / 0073686 to Crooks; U.S. Patent Application Publication No. 2017 / 0020183 to Bjorkholm; and U.S. Patent Application Publication No. 2017 / 0112183 to Bjorkholm, as well as PCT Published Application No. WO1996 / 031255 to Giolvas and PCT Published Application No. WO2018 / 083114 to Bjorkholm.

[0139] In some embodiments, the bleached activator, or a composition or product containing the bleached activator, 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 activator, or a composition or product containing the bleached activator, 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.

[0140] In some embodiments, the bleached activator can be characterized by a lightened color (e.g., "whitened") compared to the untreated activator. The color white is often defined with reference to the International Commission on Illumination (CIE) chromaticity diagram. The bleached activator, or a composition or product comprising the bleached activator, can, in certain embodiments, be characterized as being closer to pure white on the chromaticity diagram than the untreated activator, or a composition or product comprising the untreated activator.

[0141] The whiteness value of bleached active ingredients, compositions, and pouch products containing such ingredients can be determined in accordance with the International Commission on Illumination (CIE) model, for example, using a portable colorimeter to compare with a control product (see "Precise Color Communication; Color Control from Perception to Instrumentation", Konica Minolta, 2007; http: / / konicaminolta.com / instruments / about / network, which is incorporated herein by reference). The color change from white can be evaluated by the E313 whiteness index, in accordance with ASTM method E313, using the formula WI=3.388Z-3Y, where Y and Z are CIE tristimulus values, measured by a portable instrument.

[0142] 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.

[0143] 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.

[0144] Ion pairing of basic amine-containing active ingredients and organic acids In some embodiments, the oral compositions disclosed herein include an active ingredient having a basic amine functionality (i.e., the active ingredient comprises a basic amine). By "basic amine" is meant a molecule that includes at least one basic amine functionality. Examples of basic amines include, but are not limited to, alkaloids. By "basic amine functionality" is meant a group that contains a nitrogen atom that has a lone pair of electrons. The basic amine functionality is attached to or incorporated within the 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) may be affected by the nature of the neighboring atoms, the steric bulk of the molecule, and the like.

[0145] 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 a composition, or as an active ingredient in a composition, as described herein below.

[0146] In some embodiments, the active ingredient having a basic amine functionality is caffeine. In some embodiments, the active ingredient having a basic amine functionality is nicotine, such as the nicotine ingredients described herein above.

[0147] In some embodiments, at least a portion of the active ingredient having a basic amine functionality (e.g., nicotine) is combined with at least a portion of the organic acid or its alkali metal salt. Depending on a number of variables (concentration, pH, nature of the organic acid, etc.), the active ingredient having a basic amine functionality present in the composition can exist in a number of forms, including ion pairing, in solution (i.e., fully solvated), as a free base, as a cation, as a salt, or any combination thereof.

[0148] In some embodiments, at least a portion of the active ingredient having a basic amine functionality present in the composition is in ion-paired form with an organic acid or its conjugate base, as described further herein below. In some embodiments, at least a portion of the active ingredient having a basic amine functionality and the organic acid or its alkali metal salt are in the form of an ion-pair between the basic amine and the conjugate base of the organic acid.

[0149] Ion pairing describes the partial binding of oppositely charged ions in a relatively concentrated solution to form distinct chemical species called ion pairs. The strength of the binding (i.e., ion pairing) depends on the electrostatic forces of attraction between a positive ion and a negative ion (i.e., a protonated basic amine and the conjugate base of an organic acid). By "conjugate base" we mean the base that is generated from the deprotonation of the corresponding acid (e.g., benzoate ion is the conjugate base of benzoic acid).

[0150] 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 active ingredient having basic amine functionality and the conjugate base of the organic acid will be present at least in part in the form of an ion pair. Without wishing to be bound by theory, it is believed that such ion pairing may minimize chemical degradation of the active ingredient having basic amine functionality and / or may increase the oral availability of the active ingredient having basic amine functionality. At alkaline pH values ​​(e.g., about 7.5 to about 9, etc.), certain active ingredients having basic amine functionality, such as nicotine, will be present predominantly in the 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 ​​(such as from about 6.5 to about 4), certain active ingredients with basic amine functionality, such as nicotine, exist predominantly in a protonated form, which has relatively high aqueous solubility and greater stability against solvent evaporation and oxidative degradation, but low mucosal availability. In some embodiments, the stability, solubility and availability properties of nicotine can be increased by ion pairing or salt formation of nicotine with suitable organic acids and / or their conjugate bases. Specifically, moderately lipophilic nicotine-organic acid ion pairs provide favorable stability and absorption properties. Lipid solubility is conveniently measured in terms of logP, the partition coefficient of a molecule between a lipophilic phase and an aqueous phase, usually octanol and water, respectively. Octanol-water partitioning, which favors partitioning of the ion pair into octanol, predicts good absorption through the oral mucosa of active ingredients with basic amine functionality present in the composition.

[0151] As noted above, at alkaline pH values ​​(e.g., about 7.5 to about 9, etc.), nicotine exists predominantly in the free base form (and thus partitioning into octanol is high), whereas at acidic pH values ​​(e.g., about 6.5 to about 4, etc.), nicotine exists predominantly in the protonated form (and thus partitioning into octanol is low). Surprisingly, in accordance with the present disclosure, it has been found that ion pairs between certain organic acids (e.g., having logP values ​​of about 1.4 to about 8.0, such as about 1.4 to about 4.5) allow partitioning of nicotine into octanol consistent with that predicted for partitioning of nicotine into octanol at pH 8.4.

[0152] Those skilled in the art will recognize that the extent of ion pairing in the disclosed compositions, both before and during use by a user, may vary based on, for example, pH, the nature of the organic acid present in the composition, the concentration of nicotine, 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 surrogate measurements, such as partitioning between octanol and water, or membrane permeation of an aqueous solution of nicotine plus organic acid and / or their conjugate base.

[0153] organic acid As discussed hereinabove, in some embodiments, the oral compositions disclosed herein include an organic acid, an alkali metal salt thereof, or both. In some embodiments, at least a portion of the organic acid or salt thereof is in the form of an ion pair with a basic amine-containing active ingredient as described hereinabove.

[0154] 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 (-CO2 H) or sulfonic acid (-SO 2 As used herein, reference to an organic acid means 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., small amounts of an organic acid that may be naturally present in a composition component, e.g., a tobacco material).

[0155] 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.

[0156] 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.

[0157] 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).

[0158] In some embodiments, the organic acid is a carboxylic acid or a sulfonic acid. The carboxylic acid or sulfonic acid functional group can be, for example, a carboxylic acid having 1 to 20 carbon atoms (C 1 ~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.

[0159] 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.

[0160] "Cycloalkyl" as used herein refers to a carbocyclic group, which may be monocyclic or bicyclic. Cycloalkyl groups include rings having 3 to 7 carbon atoms as a monocycle or rings having 7 to 12 carbon atoms as a bicycle. Examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Cycloalkyl groups may be unsubstituted or substituted and may contain one or more sites of unsaturation (e.g., cyclopentenyl or cyclohexenyl).

[0161] 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.

[0162] "Heteroaryl" and "heterocycloalkyl," as used herein, refer to an aromatic or non-aromatic ring system, respectively, in which one or more ring atoms are heteroatoms, such as nitrogen, oxygen, and sulfur. A heteroaryl or heterocycloalkyl group contains up to 20 carbon atoms and 1-3 heteroatoms selected from N, O, and S. A heteroaryl or heterocycloalkyl may be monocyclic having 3-7 ring members (e.g., 2-6 carbon atoms and 1-3 heteroatoms selected from N, O, and S) or bicyclic having 7-10 ring members (e.g., 4-9 carbon atoms and 1-3 heteroatoms selected from N, O, and S), such as a bicyclo[4,5], [5,5], [5,6], or [6,6] system. Examples of heteroaryl groups include, by way of example and not limitation, pyridyl, thiazolyl, tetrahydrothiophenyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, thianaphthalenyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, isoxazolyl, pyrazinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, 1H-indazolyl, purinyl, 4H- Examples include quinolidinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 4aH-carbazolyl, carbazolyl, phenanthridinyl, acridinyl, pyrimidinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, furazanyl, phenoxazinyl, isochromanyl, chromanyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, benzotriazolyl, benzisoxazolyl, and isatinoyl.Examples of heterocycloalkyl include, by way of example and not limitation, dihydropyridyl, tetrahydropyridyl (piperidyl), tetrahydrothiophenyl, piperidinyl, 4-piperidonyl, pyrrolidinyl, 2-pyrrolidonyl, tetrahydrofuranyl, tetrahydropyranyl, bis-tetrahydropyranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, octahydroisoquinolinyl, piperazinyl, quinuclidinyl, and morpholinyl. Heteroaryl and heterocycloalkyl groups can be unsubstituted or substituted.

[0163] "Substituted," as used herein and as applied to any of the above alkyl, aryl, cycloalkyl, heteroaryl, and heterocyclyl groups, 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, -OCH 3 , N.H. 2 , -NHCH 3 , -N(CH 3 ) 2 , -CN, -NC(=O)CH 3 , -C(=O)-, -C(=O)NH 2 , and -C(=O)N(CH 3 ) 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.

[0164] 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.

[0165] 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.

[0166] 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.

[0167] 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.

[0168] 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.

[0169] 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.

[0170] Further non-limiting examples of organic acids that may be useful in certain embodiments include 2,2-dichloroacetic acid, 2-hydroxyethanesulfonic acid, 2-oxoglutaric acid, 4-acetamidobenzoic acid, 4-aminosalicylic acid, adipic acid, ascorbic acid (L), aspartic acid (L), alpha-methylbutyric acid, camphoric acid (+), camphor-10-sulfonic acid (+), cinnamic acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, furoic acid, and galactaric acid. , gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, isovaleric acid, lactobionic acid, lauric acid, levulinic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, oleic acid, palmitic acid, pamoic acid, phenylacetic acid, pyroglutamic acid, pyruvic acid, sebacic acid, stearic acid, and undecylenic acid. Examples of suitable acids include, but are not limited to, the list of organic acids in Table 1.

[0171] [Table 1]

[0172] 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.

[0173] 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.

[0174] 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.

[0175] 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:

[0176] [ka]

[0177] 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:

[0178] [ka]

[0179] The selection of an organic acid may further depend on additional properties, in addition to or without consideration of the logP value. For example, the organic acid should be one that is recognized as safe for human consumption and has acceptable flavor, odor, volatility, stability, etc. The determination of suitable organic acids is within the purview of one of ordinary skill in the art.

[0180] In some embodiments, more than one organic acid may be present. For example, a composition may include two, or three, or four, or more organic acids. Thus, reference herein to an "organic acid" contemplates a mixture of two or more organic acids. The relative amounts of the organic acids may vary. For example, a composition may include equal amounts of two, or three, or more organic acids, or may include different relative amounts. Thus, it is also possible to include certain organic acids (e.g., citric acid or myristic acid) that have logP values ​​outside 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 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.

[0181] For example, in some embodiments, the organic acid can include about 1 to about 5 or more molar equivalents of benzoic acid relative to nicotine, combined with, for example, about 0.2 molar equivalents of octanoic acid or a salt thereof, and 0.2 molar equivalents of decanoic acid or a salt thereof.

[0182] In some embodiments, the organic acid is a combination of any two organic acids selected from the group consisting of benzoic acid, toluic acid, benzenesulfonic acid, toluenesulfonic acid, hexanoic acid, heptanoic acid, decanoic acid, and octanoic acid. In some embodiments, the organic acid is a combination of benzoic acid, octanoic acid, and decanoic acid, or benzoic acid and octanoic acid. In some embodiments, the composition comprises citric acid in addition to one or more of benzoic acid, toluic acid, benzenesulfonic acid, toluenesulfonic acid, hexanoic acid, heptanoic acid, decanoic acid, and octanoic acid.

[0183] In some embodiments, the oral 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.

[0184] In some embodiments, the oral composition comprises benzoic acid and sodium benzoate, octanoic acid and sodium octanoate, decanoic acid and sodium decanoate, or combinations thereof. In some embodiments, the composition comprises benzoic acid and sodium benzoate. In some embodiments, the composition comprises sodium benzoate.

[0185] In some embodiments, the ratio of organic acid to sodium salt (or other alkali metal salt) 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 portion 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 depending on the pH of the composition and the pKa of the organic acid, as well as the actual relative amounts initially added to the composition.

[0186] The amount of organic acid or its alkali metal salt present in the oral composition relative to the basic amine-containing active ingredient (e.g., nicotine) can vary. Generally, as the concentration of the organic acid (or its conjugate base) increases, the proportion of nicotine that forms an ion pair with the organic acid increases. This usually results in a logP (log of the partition coefficient). 10 In some embodiments, the composition comprises from about 0.05, about 0.1, about 1, about 1.5, about 2, or about 5 to about 10, about 15, or about 20 molar equivalents of an organic acid, an alkali metal salt thereof, or a combination thereof, relative to the nicotine component, calculated as nicotine free base.

[0187] In some embodiments, the oral composition comprises 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 nicotine on a free base nicotine basis. In some embodiments, the organic acid, an alkali metal salt thereof, or a combination thereof is present in a molar ratio with 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.

[0188] In certain embodiments, the inclusion of an organic acid is sufficient to provide a pH of the oral composition of about 4.0 to about 9.0, or about 4.0 to about 8.5, or about 4.0 to about 8.0, or about 4.5 to about 7.5, or about 4.5 to about 7.0, or about 5.5 to about 7.0, or about 4.0 to about 5.5, or about 7.0 to about 9.5, etc. In some embodiments, the inclusion of an organic acid is sufficient to provide a composition with a pH of about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, about 7.0, about 7.5, about 8.0, about 8.5, or about 9.0. In some embodiments, the inclusion of an organic acid is sufficient to provide a composition pH of about 4.5 to about 6.5, e.g., from 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., from 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.

[0189] In some embodiments, the organic acid is added to the other oral composition components as a free acid, either neat (i.e., in its original solid or liquid form), or as a solution, e.g., in water. In some embodiments, the alkali metal salt of the organic acid is added to the other oral composition components, either neat or as a solution, e.g., in water.

[0190] 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).

[0191] 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.

[0192] In some embodiments, the oral composition further comprises a solubility enhancer to increase the solubility of at least one of the organic acids or salts thereof. Suitable solubility enhancers include, but are not limited to, humectants as described herein, such as glycerol or propylene glycol.

[0193] In certain embodiments, the oral composition comprises nicotine benzoate and sodium benzoate. In some embodiments, the sodium benzoate is present in a molar ratio ranging from about 1 to about 20, such as about 2, about 5, or about 10, relative to the nicotine benzoate. In some embodiments, the oral composition further comprises nicotine polacrilex. In some embodiments, the total amount of nicotine present in the composition is provided in equal amounts with the nicotine benzoate and nicotine polacrilex. In other embodiments, the oral composition comprises only nicotine polacrilex as a nicotine source, and the composition optionally comprises an organic acid component, such as sodium benzoate.

[0194] Flavoring agents and flavor granules In some embodiments, the oral composition comprises 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 the composition. Examples of sensory properties that can be modified with a flavoring agent include taste, mouthfeel, moistness, cool / heat, and / or flavor / aroma. The flavoring agent may be natural or synthetic, and the resulting flavor properties can be described as fresh, sweet, herbal, confectionery, floral, fruity, or spicy, without limitation.

[0195] 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.

[0196] 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, a "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).

[0197] 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.

[0198] The amount of flavoring utilized in the oral compositions may vary, but will typically be up to about 10% by weight, with certain embodiments characterized as having 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.

[0199] In some embodiments, the oral composition comprises flavor granules. The term "flavor granules" as used herein refers to flavors encapsulated in a matrix that results in a modified release pattern of the flavor, for example, delayed or sustained release of the flavor. Such flavor granules are generally in the form of small beads or particles (e.g., in the size range of about 14 to about 20 mesh or about 0.5 to about 1.5 mm). Without wishing to be bound by theory, it is believed that the presence of flavor granules in the oral composition provides a desirable amount of visual interest, additional texture, and / or delayed or sustained delivery of flavor to the overall composition. Such flavors may be the same or different from other flavors present in the remainder of the composition. Suitable flavor granules typically include sugar alcohols, fillers, sweeteners, humectants, colorants, and flavoring agents, or include combinations of two or more sugar alcohols, sweeteners, colorants, and flavoring agents. The amount of each component may vary depending on the desired properties of the granule and the selection of the individual components. In some embodiments, the granule comprises a sugar alcohol in an amount of about 60 to about 90% by weight; a humectant in an amount of about 15 to about 30% by weight; a filler in an amount of about 0 to about 50% by weight; a sweetener in an amount of about 0.1 to about 0.5% by weight; a flavoring agent in an amount of about 1 to about 30% by weight, with the balance being colorants. In some embodiments, the granule comprises a combination of two sugar alcohols in a total amount of about 96 to about 99% by weight, and a sweetener in an amount of about 0.1 to about 0.5% by weight, with the balance being colorants and flavoring agents.

[0200] Suitable sugar alcohols include, but are not limited to, erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and combinations thereof. In some embodiments, the sugar alcohol is isomalt, maltitol, mannitol, xylitol, sorbitol, or combinations thereof. In some embodiments, the sugar alcohol is isomalt.

[0201] Suitable humectants include, but are not limited to, glycerin, propylene glycol, 1,3-propanediol, dipropylene glycol, and combinations thereof, in some embodiments, the humectant is glycerin.

[0202] Suitable fillers include, but are not limited to, starches (e.g., from potato, wheat, rice, corn), natural cellulose, and modified cellulosic materials. In some embodiments, the filler is a cellulosic material or a cellulose derivative. In some embodiments, the filler is microcrystalline cellulose ("mcc"). MCC can be synthetic, semi-synthetic, or derived entirely from natural cellulose. MCC can be selected from the group consisting of AVICEL® grades PH-100, PH-102, PH-103, PH-105, PH-112, PH-113, PH-200, PH-300, PH-302, VIVACEL® grades 101, 102, 12, 20, and EMOCEL® grades 50M and 90M, and the like, and mixtures thereof.

[0203] The sweetener can be any sweetener or combination of sweeteners, either in natural or artificial form, or as 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 is a non-caloric artificial sweetener. In some embodiments, the sweetener is sucralose.

[0204] The flavoring and coloring agents are as described herein. In some embodiments, the coloring agent is a lake dye, such as a red or blue lake dye. As described herein above, the flavoring agent present in the granules may be the same or different from the flavoring agent present in the remainder of the composition. Ingredients

[0205] In some embodiments, the flavored granules include isomalt as a sugar alcohol, glycerin as a humectant, microcrystalline cellulose as a filler, and sucralose as a sweetener. In some embodiments, the flavored granules are an extrusion mixture of isomalt, glycerin, sucralose, microcrystalline cellulose, colorants, and flavoring agents. In some embodiments, the granules are comprised of isomalt in an amount of about 60 to about 90%, such as about 70 to about 80%, by weight; glycerin in an amount of about 16 to about 22%, such as about 18 to about 20%, by weight; microcrystalline cellulose in an amount of about 1 to about 3%, by weight; sucralose in an amount of about 0.1 to about 0.5%, such as about 0.2 to about 0.4%, by weight, with the remainder being colorants and flavoring agents. In some embodiments, the granules comprise isomalt in an amount of about 15 to about 35%, such as about 25 to about 35%, by weight; glycerin in an amount of about 15 to about 30%, such as about 18 to about 22%, by weight; microcrystalline cellulose in an amount of about 20 to about 50%, such as about 20 to about 30%, by weight; sucralose in an amount of about 0.1 to about 0.5%, such as about 0.2 to about 0.4%, by weight; flavoring agent in an amount of about 20 to about 30% by weight, with the remainder consisting of colorant.

[0206] In some embodiments, the flavored granules contain isomalt and maltitol as sugar alcohols and sucralose as a sweetener, together with flavoring and coloring agents. In some embodiments, the flavored granules are a melted, cooled, and ground mixture of isomalt, maltitol syrup, sucralose, coloring and flavoring agents. In some embodiments, the granules are comprised of isomalt in an amount of about 92 to about 96%, such as about 92 to about 94%, by weight; maltitol syrup in an amount of about 4 to about 6%, by weight; sucralose in an amount of about 0.1 to about 0.5%, such as about 0.2 to about 0.4%, by weight, with the remainder being coloring and flavoring agents.

[0207] The amount of flavor granules, if present in the oral composition, can vary, in some embodiments, the oral composition comprises about 1 to about 5% by weight of flavor granules, such as about 1, about 2, or about 3 to about 4 or about 5% by weight of flavor granules, based on the total weight of the composition.

[0208] Taste modifiers To improve the organoleptic properties of the oral 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 oral 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.

[0209] 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 this bitter taste. In some embodiments, the taste modifier is a substance that targets pain receptors (e.g., vanilloid receptors) in the oral cavity of the user, for example, to mask the bitter taste of another component (e.g., an active ingredient). In some embodiments, the taste modifier is capsaicin.

[0210] In some embodiments, the taste modifier is the amino acid gamma-aminobutyric acid (GABA), as referred to herein above in reference to amino acids. Studies in mice suggest that GABA may function in taste buds in addition to synaptic inhibition. See, for example, Dvoryanchikov et al., J Neurosci. 2011, April 13;31(15):5782-91. Without wishing to be bound by theory, GABA may suppress the perception of certain tastes, such as bitterness. In some embodiments, the composition comprises caffeine and GABA.

[0211] In some embodiments, the taste modifier is adenosine monophosphate (AMP). AMP is a natural nucleotide substance that can block the bitter taste of food or enhance sweetness. AMP does not directly modify the bitter taste, but may modify the human sensation of "bitterness" by blocking the associated receptor.

[0212] In some embodiments, the taste modifier is lactisol. Lactisol is a sweet receptor antagonist. Temporarily blocking sweet receptors can, for example, enhance umami taste.

[0213] 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 typically comprise less than about 10% by weight of the total weight of the oral composition (e.g., from about 0.01% by weight, about 0.05% by weight, about 0.1% by weight, or about 0.5% by weight, up to about 1% by weight, about 5% by weight, or about 10% by weight, based on the total weight of the oral composition).

[0214] Sweetener To improve the sensory and / or physical properties of the oral composition, one or more sweeteners may be added in addition to any sugar or sugar alcohol that may be present as a bulking agent. The sweetener or mixture of sweeteners, when present in the oral composition, is generally present in an amount of less than about 1% by weight of the composition, such as from about 0.1 to about 1% by weight or from about 0.3 to about 0.6% by weight, based on the total weight of the oral composition.

[0215] 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, isomaltulose, mannose, galactose, lactose, stevia, honey, etc. Examples of artificial sweeteners include sucralose, maltodextrin, saccharin, aspartame, acesulfame K, neotame, etc. In some embodiments, the sweetener is an artificial sweetener. In some embodiments, the artificial sweetener is selected from the group consisting of sucralose, acesulfame K, aspartame, and mixtures thereof.

[0216] Moisturizer In certain embodiments, one or more humectants may be used in the oral compositions of the present disclosure. The humectant may serve additional functions, such as softening or sweetening the oral composition. When included, the humectant is typically provided in an amount sufficient to provide the oral composition with the desired moisture or other physical characteristics. When present, the humectant may be present in an amount of about 0.01% to about 5%, such as about 0.1 to about 3% by weight or about 1 to about 2% by weight, based on the total weight of the oral composition. Examples of suitable humectants include, but are not limited to, glycerin, 1,2-propanediol (propylene glycol), 1,3-propanediol, dipropylene glycol, and the like. In some embodiments, the humectant is glycerin.

[0217] Tobacco Materials In some embodiments, the oral 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.

[0218] 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.

[0219] In some embodiments, Nicotiana species can be selected for the content of various compounds present therein. For example, plants can be selected based on being plants that produce relatively large amounts of one or more compounds that one wishes to isolate. In certain embodiments, Nicotiana species plants (e.g., Nicotiana galpaocomun) are specifically cultivated for their abundance of these foliar compounds. Tobacco plants can be grown in greenhouses, growth chambers, or outdoor fields, or grown hydroponically.

[0220] 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).

[0221] In certain embodiments, the tobacco material comprises a solid tobacco material selected from the group consisting of lamina and stem. The tobacco used in the mixture most preferably comprises tobacco lamina or a mixture of tobacco lamina and stem, at least a portion of which is smoked. A portion of the tobacco in the mixture may have a processed form, such as processed tobacco stems (e.g., cut rolled stems, cut rolled expanded stems, or cut puff stems), or volume-expanded tobacco (e.g., puffed tobacco, e.g., dry ice expanded tobacco (DIET)). See, for example, the tobacco expansion processes described in U.S. Patent No. 4,340,073 to de la Burde et al.; U.S. Patent No. 5,259,403 to Guy et al.; and U.S. Patent No. 5,908,032 to Poindexter et al.; and U.S. Patent No. 7,556,047 to Poindexter et al., all of which are incorporated by reference. In addition, the mixture may incorporate tobacco that is optionally fermentable. See the types of tobacco processing techniques described in Atchley et al., PCT WO2005 / 063060, which is incorporated herein by reference.

[0222] Tobacco materials are typically used in a form that can be described as particulate (i.e., shredded, milled, granulated, or powdered form). The manner in which tobacco materials are provided in finely divided or powdered form types can vary. Preferably, plant parts or pieces are pulverized, milled, or pulverized into particulate form using equipment and techniques for milling, milling, and the like. Most preferably, the plant material is in a relatively dry form during milling or milling using equipment such as hammer mills, cutter heads, air controlled mills, and the like. For example, tobacco parts or pieces can be milled or milled when their moisture content is less than about 15 weight percent or less than about 5 weight percent. Most preferably, tobacco materials are utilized in the form of parts or pieces having an average particle size between 1.4 millimeters and 250 microns. In some cases, the tobacco particles can be sized to pass a screen mesh to obtain the required particle size range. If desired, air classification equipment can be used to ensure collection of small sized tobacco particles of the desired size or size range. If desired, different size pieces of granulated tobacco can be mixed together.

[0223] The manner in which tobacco is provided in finely divided or powder-type form may vary. Preferably, tobacco parts or pieces are pulverized, milled, or pulverized into a powder-type form using equipment and techniques for milling, milling, and the like. Most preferably, the tobacco is in a relatively dry form during milling or milling using equipment such as hammer mills, cutter heads, air-controlled mills, and the like. For example, tobacco parts or pieces can be milled or milled when their moisture content is less than about 15 weight percent to less than about 5 weight percent. For example, tobacco plants or portions thereof can be separated into individual parts or pieces (e.g., leaves can be removed from the stems, and / or stems and leaves can be removed from the trunks). Harvested plants or individual parts or pieces can be further subdivided into parts or pieces (e.g., leaves can be chopped, cut, powdered, pulverized, milled, or milled into pieces or portions, which pieces or portions can be characterized as filler-type pieces, granules, granular, or fine powders). The plant, or a portion thereof, can be subjected to an external force or pressure (e.g., by pressing or rolling). When such processing conditions are performed, the plant or a portion thereof can have a moisture content that approximates its natural moisture content (e.g., its moisture content immediately after harvesting), a moisture content achieved by adding moisture to the plant or a portion thereof, or a moisture content resulting from drying the plant or a portion thereof. For example, powdered, pulverized, milled, or milled pieces of a plant or a portion thereof can have a moisture content of less than about 25 weight percent, often less than about 20 weight percent, and frequently less than about 15 weight percent.

[0224] For the preparation of oral compositions, harvested plants of Nicotiana species are usually subjected to a curing process. The tobacco material incorporated in the oral compositions disclosed herein is 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.

[0225] In certain embodiments, tobacco materials that may be utilized include flue-cured or Virginia (e.g., K326), Burley, sun-cured (e.g., Indian Kurnool and Oriental tobaccos, including Katerini, Pre-Rip, Komotini, Xanthi, and Yambol tobaccos), Maryland, dark, dark-fired, dark air-cured (e.g., Madol, Pasanda, Cubano, Jatin, and Bezuki tobaccos), light air-cured (e.g., North Wisconsin and Galpao tobaccos), Indian air-cured, Red Russian, and Rustica tobaccos, as well as various other rare or specialty tobaccos and various blends of any of the aforementioned tobaccos.

[0226] The tobacco material can also have a so-called "blend" form. For example, the tobacco material can include a mixture of flue-cured, burley (e.g., Malawi Burley) and oriental tobacco parts or pieces (e.g., tobacco composed of or derived from tobacco lamina, or a mixture of tobacco lamina and tobacco stem). For example, a representative blend can incorporate, on a dry weight basis, about 30 to about 70 parts burley tobacco (e.g., lamina, or lamina and stem), and about 30 to about 70 parts flue-cured tobacco (e.g., stem, lamina, or lamina and stem). Other exemplary tobacco blends incorporate, on a dry weight basis, about 75 parts flue-cured tobacco, about 15 parts burley tobacco, and about 10 parts oriental tobacco; or about 65 parts flue-cured tobacco, about 25 parts burley tobacco, and about 10 parts oriental tobacco; or about 65 parts flue-cured tobacco, about 10 parts burley tobacco, and about 25 parts oriental tobacco. Other exemplary tobacco blends incorporate, on a dry weight basis, from about 20 to about 30 parts Oriental tobacco and from about 70 to about 80 parts flue-cured tobacco.

[0227] The tobacco material used in the present disclosure can be subjected to, for example, fermentation, bleaching, etc. If desired, the tobacco material can also be subjected to, for example, irradiation, pasteurization, or otherwise controlled heat treatment. Such treatment processes are detailed, for example, in U.S. Patent No. 8,061,362 to Mua et al., which is incorporated herein by reference. In certain embodiments, the tobacco material can be treated with water and an additive capable of inhibiting the reaction of asparagine to form acrylamide upon heating of the tobacco material (e.g., an additive selected from the group consisting of lysine, glycine, histidine, alanine, methionine, cysteine, glutamic acid, aspartic acid, proline, phenylalanine, valine, arginine, compositions incorporating divalent and trivalent cations, asparaginase, certain non-reducing sugars, certain reducing agents, phenolic compounds, certain compounds having at least one free thiol group or functional group, oxidizing agents, oxidation catalysts, natural plant extracts (e.g., rosemary extract), and combinations thereof). See, for example, the types of treatment processes described in U.S. Patent Publication Nos. 8,434,496, 8,944,072, and 8,991,403 to Chen et al., all of which are incorporated herein by reference. In certain embodiments, this type of treatment is useful when the original tobacco material is subjected to heat in the previously described processes.

[0228] 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.

[0229] 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.

[0230] 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.

[0231] 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.

[0232] Typical inclusion ranges for tobacco material may vary depending on the nature and type of tobacco material and the intended effect of the composition, with exemplary ranges being up to about 30% (or up to about 20%, or up to about 10%, or up to about 5%) by weight of the total oral composition (e.g., about 0.1 to about 15%). In some embodiments, oral compositions of the present disclosure may be characterized as being completely free or substantially free of tobacco material (other than purified nicotine as the active ingredient). For example, certain embodiments may be characterized as having less than 1% by weight, or less than 0.5% by weight, or less than 0.1% by weight tobacco material, or 0.01% by weight tobacco material, or 0% by weight tobacco material.

[0233] salt In some embodiments, the oral compositions include commonly used salts (e.g., alkali metal salts) in an amount sufficient to impart the desired sensory attributes to the product. Non-limiting examples of suitable salts include sodium chloride, potassium chloride, ammonium chloride, flour salts, sodium acetate, sodium citrate, and the like.

[0234] A representative amount of salt, if present, is at least about 0.5% by weight, such as at least about 1% by weight, such as at least about 1.5% by weight. In some embodiments, the oral composition may include salt in an amount of from about 0.5% to about 10% by weight, such as from about 1% to about 7.5% by weight, such as from about 1.5% to about 5% by weight, based on the total weight of the oral composition.

[0235] Buffer In certain embodiments, the oral composition may include a pH adjusting agent or a 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. In some embodiments, the buffering agent is selected from the group consisting of sodium citrate, sodium carbonate, sodium bicarbonate, sodium phosphate, ammonium phosphate, and mixtures thereof. In some embodiments, the buffering agent is sodium citrate.

[0236] When present, the buffering agent is typically present in an amount of less than about 5% by weight of the composition, for example, from about 0.5% to about 5% by weight, 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 oral composition.

[0237] Coloring agent Coloring agents can be used in an amount sufficient to provide the oral composition with desired physical attributes. Natural or synthetic coloring agents, such as natural or synthetic dyes, food grade coloring agents, and pharmaceutical grade coloring agents, may be used. Examples of coloring agents include various dyes and pigments, such as caramel coloring agents and titanium dioxide. Natural coloring agents, such as curcumin, beet juice extract, spirulina, as well as various synthetic pigments, may also be used. In some embodiments, the coloring agent is a lake dye, such as red or blue aluminum lake dye. The amount of coloring agent utilized in the oral composition may vary, but when present, is usually about 0.1%, about 0.5%, or about 1% to about 3% by weight, such as about 3% by weight, based on the total weight of the oral composition.

[0238] Oral Care Additives In some embodiments, the oral 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 oral 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, if present, are at least about 1%, often at least about 3%, and frequently at least about 5% of the total weight of the composition. The amount of oral care additive in the oral composition typically does not exceed about 30%, often does not exceed about 25%, and frequently does not exceed about 20% by total weight of the oral composition.

[0239] Other Additives Other additives may be included in the oral composition. For example, the oral composition is 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), preservatives (e.g., potassium sorbate, sodium benzoate, calcium propionate, etc.), zinc or magnesium salts selected to be relatively water soluble for more water soluble compositions (e.g., magnesium gluconate or zinc gluconate), or zinc or magnesium salts selected to be relatively water insoluble for less water soluble compositions (e.g., magnesium oxide or zinc oxide), or combinations thereof. See, for example, representative components, combinations of components, relative amounts of the components, and modes and methods for utilizing the components, as described in U.S. Patent No. 9,237,769 to Mua et al., U.S. Patent No. 7,861,728 to Holton, Jr. et al., U.S. Patent Application Publication No. 2010 / 0291245 to Gao et al., and U.S. Patent Application Publication No. 2007 / 0062549 to Holton, Jr. et al., each of which is incorporated herein by reference. Typical inclusion ranges for such additional additives can vary depending on the nature and function of the additive and its intended effect on the final composition, with exemplary ranges being up to about 10% by weight (e.g., from about 0.1 to about 5% by weight), based on the total weight of the composition.

[0240] For example, preservatives (such as potassium sorbate, sodium benzoate, calcium propionate, etc.), if present, may be included in the oral compositions in an amount from about 0.001% to about 5% by weight of the composition, such as from about 0.01% to about 2.5% by weight of the composition, such as from about 0.05% to about 1% by weight of the oral composition.

[0241] 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 oral composition). 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 WO2010 / 132444 to Atchley, which is incorporated herein by reference.

[0242] Built for oral use The oral composition described herein is designed for oral use. The term "designed for oral use" as used herein means that the oral composition is provided in such a form that during use, one or more components (e.g., flavoring agent and / or active ingredient) of the oral composition are carried into the mouth of the user by the saliva in the mouth of the user.In certain embodiments, the oral composition is adapted to deliver a component to the user via the oral mucosa of the user, the digestive system of the user, or both, and in some cases, the component is an active ingredient that can be absorbed via the oral mucosa or absorbed via the digestive tract when the oral composition is used.

[0243] The oral compositions described herein are in a solid chewable form, meaning that the oral compositions have a light resilience or "bounce" when chewed and have a desired low malleability. Such oral compositions are referred to herein as "chewables," "chews," or "chewing gums." Oral compositions in chewable form are generally in the form of non-dissolving gums, where only certain components (e.g., active ingredients, flavors, bulking agents, sweeteners, etc.) dissolve, leaving behind a non-dissolving matrix. As used herein, the terms "dissolve," "dissolving," and "soluble" refer to oral compositions having water-soluble components (e.g., active ingredients, flavors, bulking agents, sweeteners, etc.) that interact with the moisture in the oral cavity and go into solution, thus causing gradual consumption of at least a portion of the oral composition. Desired texture properties, such as for chewable oral compositions, can include one or more of adhesiveness, cohesiveness, density, granularity, stickiness, hardness, weight, moisture absorption, moisture release, oral coating, roughness, slipperiness, smoothness, viscosity, and wetness. In some embodiments, the oral composition includes a coating, as described herein below, which can serve to provide additional properties to the oral composition (e.g., crispiness, immediate release of certain components, additional flavors, or active ingredients).

[0244] The physical format of the oral composition can vary. For example, the oral composition can be in tablet form (such as a compressed tablet) having any desired shape, or in the form of a sheet of any desired dimensions (thickness, width and length). In some embodiments, the oral composition can be in the form of a tablet of any desired shape, such as a conventional stick (i.e., having a length greater than its width and a thickness substantially less than either its length or width), or a substantially square or round format of any desired thickness.

[0245] In some embodiments, the oral composition comprises an outer coating. The outer coating may be hard, soft, in the form of a film, or any combination thereof. The coating may comprise from about 0.1 to about 75% by weight of the coated oral composition. In some embodiments, the oral composition comprises an outer coating in the form of a film. Such a film coating may be provided by a film former such as a cellulose derivative, modified starch, dextrin, gelatin, zein, shellac, gum (e.g., gum arabic or vegetable gum), wax, synthetic polymer, or combinations thereof. In some embodiments, the oral composition comprises an outer coating in the form of a hard coating. The hard coating provides a sweet crunchy layer, which may further act to protect the softer gum center. The hard coating may be sugar-based or sugar-free. Suitable hard coatings may comprise one or more sugars, such as sucrose or dextrose, or one or more sugar alcohols, such as sorbitol, maltitol, mannitol, xylitol, erythritol, lactitol, isomalt, etc. In some embodiments, the coating comprises isomalt.

[0246] In some embodiments, the coating further comprises a flavoring agent, which may be the same as or different from any flavoring agent provided in the oral composition, an active ingredient, which may be the same as or different from any active ingredient provided in the oral composition, a coloring agent, or any combination thereof. In embodiments including a coating that includes an active ingredient, a flavoring agent, or both, the coated oral composition can provide, for example, immediate, delayed, sustained, and / or individualized delivery of various flavors and active ingredients.

[0247] Preparation of oral compositions Generally, the oral compositions disclosed herein are prepared by combining the various components of the oral composition (e.g., gum base, bulking agent, active ingredient, flavoring agent, etc.) to obtain a homogenous mixture. The manner in which the various components of the oral composition (e.g., gum base, bulking agent, active ingredient, flavoring agent, etc.) are combined can vary. Generally, the gum base is combined with the bulking agent, active ingredient and / or flavoring agent, moisturizer, and any additional components of the composition, and then mixed.

[0248] The various components of the oral composition can be contacted, combined, or mixed together using any mixing technique or device known in the art. Any mixing method that brings the oral composition components into intimate contact can be used, such as a mixing device that features an impeller or other agitating structure. Examples of mixing devices include casing drums, conditioning cylinders or drums, liquid spray devices, conical 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.

[0249] In some embodiments, the gum base is warmed prior to combining with the other components to facilitate mixing. For example, the gum base may be heated by any suitable means (such as a steam kettle, oven, microwave irradiation, etc.) for a sufficient time and at a suitable temperature so that the gum base becomes soft and malleable. In some embodiments, the gum base is heated to a temperature of about 50 to about 100° C., such as about 70 to about 90° C. In some embodiments, such heating is accomplished by microwave heating for a period of time, such as about 1 minute to about 10 minutes. The warm gum base is typically mixed for a sufficient time to ensure homogeneity and a smooth consistency.

[0250] The remaining components of the oral composition can then be added sequentially or simultaneously and then mixed. In certain embodiments, the solid (e.g., dry particles or particulates) and liquid (e.g., wet or solution form) components are added separately. For example, in some embodiments, the wet components (e.g., bulking agent in liquid form, active ingredient in solution form, humectant, etc.) are mixed together to form a liquid mix, a quantity of the liquid mix is ​​added, and then mixed. Subsequently, the dry components (e.g., bulking agent, organic acid, etc.) are mixed together to form a dry mix, a quantity of the dry mix is ​​added, and then mixed. This alternating addition is repeated until all components are added. In certain embodiments, approximately 1 / 3 of the liquid mix is ​​added per addition, and approximately 1 / 3 of the dry mix is ​​added per addition. In some embodiments, the active ingredient (e.g., nicotine or nicotine salt) is added separately from the wet mix or dry mix. In some embodiments, the sweetener is added separately from the wet mix or dry mix. In some embodiments, the sweetener is not part of the dry mix, but is added with the first portion thereof. In some embodiments, the composition includes nicotine polacrilex, and the nicotine polacrilex is added with one or more portions of the dry ingredient mix. In some embodiments, the flavoring agent is not part of the wet mix or dry mix, but is added after all dry and wet components have been combined. Without wishing to be bound by any particular theory, it is believed that the portioned and separate addition of sweeteners and flavoring agents can provide a more sustained and uniform delivery of sweeteners and / or flavoring agents during consumption of the oral composition.

[0251] In some embodiments, the organic acid component is an alkali metal salt of an organic acid, such as sodium benzoate. In some embodiments, the organic acid component (e.g., sodium benzoate) is added to the mixture after all of the dry and wet components have been combined, but before the flavoring agents are added.

[0252] In some embodiments, the composition further comprises flavor granules as described herein above. Such granules can be generally prepared by forming a flavor mix, combining the flavor mix with glycerin (or other humectant) and isomalt (or other sugar alcohol), thoroughly mixing, and extruding through a die. In some embodiments, the flavor mix is ​​prepared by combining a filler such as microcrystalline cellulose, a colorant (e.g., a red or blue dye such as a lake), and one or more flavoring and sweetening agents (e.g., a non-caloric sweetener such as sucralose). The mix is ​​then extruded through a die (e.g., a 0.5-1.5 mm die) to form beads, which may be optionally spheronized. The beads generally have a size ranging from about 14-20 mesh or about 0.5 to about 1.5 mm. In another embodiment, the flavor granules are prepared by combining one or more sugar alcohols (e.g., isomalt, maltitol, or a combination thereof), a sweetener (e.g., a non-caloric sweetener such as sucralose), and a colorant (e.g., a red or blue dye such as lake) and one or more flavoring agents, heating the mix until it is in a liquid form, cooling to form a solid mass, breaking or grinding the solid mass into particles, and sieving the particles to obtain granules of a desired size. The flavor granules (beads or microparticles) are generally incorporated into the composition as is (e.g., without drying or further processing), optionally together with another flavoring agent. After the addition of the granules, the composition is mixed for a time sufficient to distribute them evenly throughout the composition. Usually, about 45 seconds of mixing is required.

[0253] The entire mixing process to prepare the composition typically takes from about 5 minutes to about 30 minutes, depending on the batch size. Those skilled in the art will recognize that variations of this or other mixing procedures may be followed.

[0254] After mixing, the oral composition is removed from the mixer. The oral composition may be milled with various substances to aid processing (e.g., to reduce viscosity) or to modify the initial taste characteristics of the oral composition. Such substances may include sucrose, mannitol, starch, calcium carbonate, talc, lactitol, lactose, and combinations thereof. The oral composition is then extruded, wound, compressed, and the like. In some embodiments, the oral composition is processed through a sheeter to obtain a desired thickness. For example, the oral gum base may undergo multiple passes through at least one, and preferably several, sets of counter-rotating reduction rollers and finishing rollers to stretch the oral composition and reduce its thickness. For adhesive gums, this thickness will generally be in the range of about 0.05 to about 0.10 inches, such as about 0.06 to about 0.08 inches, and for tablet gums, this may be in the range of about 0.15 to about 0.3 inches, such as about 0.18 to 0.25 inches. In some embodiments, the oral composition may undergo further processing such as drying, hardening, aging, etc. The oral composition is then packaged in a desired format. EXAMPLES

[0255] Aspects of the present invention are more fully illustrated by the following examples, which are presented to illustrate certain specific aspects of the invention and should not be construed as limiting the invention.

[0256] Example 1: Preparation of flavored chewing gum containing nicotine benzoate Chewing gum tablets containing flavorings and approximately 2 mg of nicotine each were prepared using the formulation components presented in Table 2.

[0257] Sorbitol, isomalt and sodium benzoate were combined to obtain a dry mix. Separately, a solution of maltitol syrup, glycerin and nicotine benzoate was combined to form a liquid mix. A gum base (Artica T; CAFOSA GUM S / A, Barcelona, ​​Spain) was heated in a microwave oven at low power for approximately 5 minutes to soften it. The heated and softened gum base was mixed by hand until uniform and transferred to the bowl of a commercial mixer. Approximately 1 / 3 of the liquid mix was added to the gum base and then mixed for 2 minutes. Approximately 1 / 3 of the dry mix was added to the gum base-liquid mix with sucralose and then mixed for 2 minutes. The addition of the dry mix and the liquid mix were repeated twice each and then mixed for an additional 2 minutes in each case to combine the remaining dry mix and liquid mix. Flavoring was added to this mixture and then mixed for 45 seconds. The mixture was removed from the mixer bowl, powdered with mannitol powder, and then passed through a sheeter to obtain a composition of uniform thickness. Square tablets, each weighing 1.65 g, were die cut from the sheet of composition.

[0258] [Table 2]

[0259] [Example 2] Preparation of colored flavor granules Colored flavor granules (red and blue) were prepared using the formulation components presented in Table 3.

[0260] The microcrystalline cellulose, colorant (either red or blue lake dye), and flavor were mixed together to form a flavor mix. To this mix, glycerin and isomalt were added and then mixed to obtain a homogenous composition. The homogenous composition was then extruded through a 1.5 mm die to form beads having a size of 14-20 mesh. The beads were used directly in the following examples.

[0261] [Table 3]

[0262] Example 3: Preparation of flavored chewing gum containing nicotine benzoate and flavor granules Chewing gum tablets containing flavorings and approximately 2 mg of nicotine each were prepared using the formulation components presented in Table 4.

[0263] Gum base (Artica T; CAFOSA GUM S / A, Barcelona, ​​Spain) was warmed in a microwave oven for approximately 5 minutes at low power to soften. Separately, maltitol syrup and glycerin were combined to form a liquid mixture. Separately, sorbitol and isomalt were combined to obtain a dry mixture.

[0264] The heated softened gum base was mixed by hand until uniform and transferred to the bowl of a commercial mixer. Approximately 1 / 3 of the liquid mixture was added to the gum base with the nicotine benzoate solution and then mixed for 2 minutes. Approximately 1 / 3 of the dry mixture was added to the gum base-liquid mixture with the sucralose through a 20 mesh sieve and then mixed for 2 minutes. The addition of the liquid and dry mixtures was repeated twice each and then mixed for an additional 2 minutes each time to blend the remaining dry and liquid mixtures. Sodium benzoate was added to the mixture, followed by flavoring, and flavor granules (Example 2) were added to the mixture and then mixed for 45 seconds. The mixture was removed from the mixer bowl, pulverized with mannitol powder, and then passed through a sheeter to obtain a composition of uniform thickness. The total batch weight was 2 kg. Square tablets weighing 1.74 g each were die cut from the sheet of composition.

[0265] [Table 4]

[0266] Example 4: Preparation of flavored chewing gum containing nicotine benzoate, nicotine polacrilex and flavor granules Chewing gum tablets containing flavorings and approximately 2 mg of nicotine each (equal parts of nicotine from nicotine benzoate and nicotine polacrilex) were prepared using the formulation components presented in Table 5.

[0267] Gum base (Artica T; CAFOSA GUM S / A, Barcelona, ​​Spain) was warmed in a microwave oven for approximately 5 minutes at low power to soften. Separately, maltitol syrup and glycerin were combined to form a liquid mixture. Separately, sorbitol and isomalt were combined to obtain a dry mixture.

[0268] The heated softened gum base was mixed by hand until uniform and transferred to the bowl of a commercial mixer. Approximately 1 / 3 of the liquid mixture was added to the gum base with the nicotine benzoate solution and then mixed for 2 minutes. Approximately 1 / 3 of the dry mixture was added to the gum base-liquid mixture with the sucralose and nicotine polacrilex through a 20 mesh sieve and then mixed for 2 minutes. The addition of the liquid and dry mixtures was repeated twice each and then mixed for an additional 2 minutes each time to blend the remaining dry and liquid mixtures. Sodium benzoate was added to the mixture, followed by flavoring, and flavor granules (Example 2) were added to the mixture and then mixed for 45 seconds. The mixture was removed from the mixer bowl and pulverized with mannitol powder and then passed through a sheeter to obtain a composition of uniform thickness. The total batch weight was 2 kg. Square tablets, each weighing 1.74 g, were die cut from the sheet of composition.

[0269] [Table 5]

[0270] Example 5: Preparation of flavored chewing gum containing nicotine polacrilex and flavor granules Chewing gum tablets containing flavorings and approximately 2 mg of nicotine each (from nicotine polacrilex) were prepared using the formulation components presented in Table 6.

[0271] Gum base (Artica T; CAFOSA GUM S / A, Barcelona, ​​Spain) was warmed in a microwave oven for approximately 5 minutes at low power to soften. Separately, maltitol syrup and glycerin were combined to form a liquid mixture. Separately, sorbitol and isomalt were combined to obtain a dry mixture.

[0272] The heated softened gum base was mixed by hand until uniform and transferred to the bowl of a commercial mixer. Approximately 1 / 3 of the liquid mixture was added to the gum base and then mixed for 2 minutes. Approximately 1 / 3 of the dry mixture was added to the gum base-liquid mixture along with sucralose and nicotine polacrilex through a 20 mesh sieve and then mixed for 2 minutes. The addition of the liquid and dry mixtures was repeated twice each and then mixed for an additional 2 minutes each time to blend the remaining dry and liquid mixtures. Sodium benzoate was added to the mixture, followed by flavoring, and flavor granules (Example 2) were added to the mixture and then mixed for 45 seconds. The mixture was removed from the mixer bowl, pulverized with mannitol powder, and then passed through a sheeter to obtain a composition of uniform thickness. The total batch weight was 2 kg. Square tablets weighing 1.74 g each were die cut from the sheet of composition.

[0273] [Table 6]

[0274] Example 6: Preparation of reduced size colored flavor granules Colored flavor granules (red and blue) were prepared using the formulation components presented in Table 7.

[0275] Microcrystalline cellulose, colorant (either red or blue lake dye), and flavoring are mixed together to form a flavoring mix. To this mix, glycerin and isomalt are added and then mixed to obtain a homogeneous composition. The homogeneous composition is then extruded through a 0.5 mm die to form beads, which are then spheronized and sieved to obtain beads of desired size.

[0276] [Table 7]

[0277] Example 7: Alternative preparation of colored flavor granules Colored flavor granules (red and blue) were prepared using the formulation components presented in Table 8.

[0278] Isomalt, maltitol syrup, colorant (either red or blue lake dye), sucralose, and flavor were combined and heated with mixing to form a fluid liquid mixture, which was then cooled to form a solid mass that was crushed and sieved to obtain flavor particles having the desired particle size range (approximately 0.5 mm).

[0279] [Table 8]

[0280] Example 8: Alternative preparation of colored flavor granules - high flavor loading Colored flavor granules were prepared using the formulation components presented in Table 9.

[0281] The microcrystalline cellulose, colorant (either red or blue lake dye), and flavor are mixed together to form a flavor mix. To this mix, glycerin and isomalt are added and then mixed to obtain a homogeneous composition. The homogeneous composition is then extruded through a 0.5 mm die to form beads, which are then spheronized and sieved to obtain beads of the desired size.

Table 9

Claims

1. Gum base one or more bulking agents an active ingredient having a basic amine functionality, and an organic acid, an alkali metal salt of an organic acid, or a combination thereof wherein at least a portion of the active ingredient having basic amine functionality is bound to at least a portion of the organic acid or alkali metal salt thereof, the binding being 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 both forms.

2. The oral composition of claim 1 in the form of a chewing gum.

3. 10. The oral composition of claim 1, wherein at least a portion of the active ingredient having basic amine functionality is in the form of an ion pair between a basic amine and a conjugate base of an organic acid.

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

5. The oral composition of claim 1, wherein the organic acid has a log P value of 1.4 to 4.

5.

6. The oral composition of claim 1, wherein the organic acid has a log P value of 2.5 to 3.

5.

7. 10. The oral composition of claim 1, wherein the organic acid has a log P value of 4.5 to 12, and the composition further comprises a solubility enhancer.

8. The oral composition of claim 7, wherein the dissolution enhancer is glycerol or propylene glycol.

9. 10. The oral composition of claim 1, comprising from 0.05, 0.1, 1, 1.5, 2, or 5 to 10, 15, or 20 molar equivalents of the organic acid, its alkali metal salt, or combination thereof, calculated as amine free base, relative to the active ingredient having basic amine functionality.

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

11. 10. The oral composition of claim 1, wherein the organic acid comprises benzoic acid, a menthyl monoester of a dicarboxylic acid, or a tocopherol monoester, or a combination thereof.

12. 12. The oral composition of claim 11, wherein the dicarboxylic acid is malonic acid, succinic acid, glutaric acid, adipic acid, fumaric acid, maleic acid, or a combination thereof.

13. The oral composition of claim 1 , wherein the organic acid comprises tocopherol succinate, monomenthyl succinate, monomenthyl fumarate, monomenthyl glutarate, or a combination thereof.

14. 14. The oral composition of claim 13 further comprising benzoic acid and sodium benzoate.

15. The oral composition of claim 1 comprising benzoic acid and sodium benzoate.

16. The oral composition according to claim 1 , comprising the organic acid and an alkali metal salt of the organic acid.

17. 17. The oral composition of claim 16, wherein the alkali metal is sodium or potassium.

18. 2. The oral composition according to claim 1, wherein the ratio of the organic acid to the alkali metal salt of the organic acid is 0.1 to 10.

19. The oral composition according to claim 1, wherein the pH of the composition is 4.0 to 9.

0.

20. The oral composition according to claim 1, wherein the pH of the composition is 4.5 to 7.

21. The oral composition according to claim 1, wherein the pH of the composition is 5.5 to 7.

22. The oral composition according to claim 1, wherein the pH of the composition is 4.0 to 5.

5.

23. The oral composition according to claim 1, wherein the pH of the composition is 7.0 to 9.

0.

24. 10. The oral composition of claim 1, wherein the active ingredient having basic amine functionality is nicotine.

25. 25. The oral composition of claim 24, wherein the nicotine is present in an amount of 0.001 to 10% by weight of the composition, calculated as the free base based on the total weight of the composition.

26. 25. The oral composition of claim 24, comprising a nicotine salt such as nicotine benzoate, nicotine polacrilex, or a combination thereof.

27. The oral composition of claim 1 , wherein the gum base comprises a synthetic elastomer.

28. 28. The oral composition of claim 27, wherein the gum base further comprises a plasticizer, a filler, a softener, an emulsifier, a wax, an anti-tack agent, an antioxidant, or a combination thereof.

29. The oral composition of claim 1 , wherein the bulking agent comprises one or more sugar alcohols.

30. As the bulking agent, sorbitol in an amount of 25 to 50% by weight, maltitol in an amount of 10-20% by weight, and Isomalt in an amount of 10-20% by weight (each based on the total weight of the oral composition) The oral composition of claim 1 comprising a combination of:

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

32. 10. The oral composition of claim 1, further comprising one or more additional active ingredients selected from the group consisting of nutraceuticals, botanicals, stimulants, amino acids, vitamins, cannabinoids, cannabis analogs, and terpenes.

33. the gum base in an amount of 20 to 30% by weight based on the total weight of the oral composition; the bulking agent in an amount of 50 to 80% by weight based on the total weight of the oral composition, the bulking agent comprising one or more sugar alcohols; a humectant in an amount of 1 to 2% by weight based on the total weight of the oral composition; Nicotine benzoate, and Sodium Benzoate The oral composition of claim 1 , comprising:

34. 34. The oral composition of claim 33, further comprising nicotine polacrilex.

35. the gum base in an amount of 20 to 30% by weight based on the total weight of the oral composition; the bulking agent in an amount of 50 to 80% by weight based on the total weight of the oral composition, the bulking agent comprising one or more sugar alcohols; a humectant in an amount of 1 to 2% by weight based on the total weight of the oral composition; Nicotine polacrilex, and Sodium Benzoate The oral composition of claim 1 , comprising:

36. An oral composition according to any one of claims 1 to 35, further comprising flavour granules.

37. The flavor granules are Sugar alcohol in an amount of 60-90% by weight, a humectant in an amount of 16-22% by weight; a sweetener in an amount of 0.1 to 0.5% by weight; Filler in an amount of 1-3% by weight, colorants, and Flavoring agent (Each amount by weight is based on the total weight of the flavor granules.) 37. The oral composition of claim 36, comprising:

38. The flavor granules are Sugar alcohols in an amount of 15-35% by weight, Filler in an amount of 20-50% by weight, Flavoring agent in an amount of 20-30% by weight, a humectant in an amount of 15-30% by weight; a sweetener in an amount of 0.1 to 0.5% by weight, and Coloring agent in an amount of 0.1 to 1.5% by weight (Each amount by weight is based on the total weight of the flavor granules.) 37. The oral composition of claim 36, comprising:

39. 38. The oral composition of claim 37, wherein the sugar alcohol is isomalt, the filler is microcrystalline cellulose, the humectant is glycerin, and the sweetener is sucralose.

40. The flavor granules are a combination of two sugar alcohols in an amount of 96 to 99% by weight in total; Sweeteners in an amount of 0.1 to 0.5% by weight, and colorants and flavoring agents making up the remainder of the flavor granules.

37. The oral composition of claim 36, comprising:

41. The flavor granules are Isomalt in an amount of 92-96% by weight, Maltitol syrup in an amount of 4-6% by weight, Sucralose in an amount of 0.1 to 0.5% by weight It consists of The remainder consists of colorants and flavoring agents. The oral composition of claim 40.