Oral Product Tablets and Manufacturing Method

Abstract

The present disclosure provides a product designed for oral use and a method for making the product. The product comprises a plurality of granules, the granules comprising at least one filler; at least one sugar alcohol; cellulose ether, polyvinylpyrrolidone or a combination thereof; and at least one active ingredient, at least one flavoring agent or a combination thereof. The product may be in the form of a granule, or may be in the form of a tablet or pellet.

Description

[Technical field]

[0001] The present disclosure relates to products intended for human use. The products are adapted for oral use and for delivery of substances such as flavorants and / or active ingredients during use. Such products may include tobacco-derived products or may be tobacco-free alternatives. [Background technology]

[0002] Tobacco can be enjoyed in so-called "smokeless" forms. Particularly popular smokeless tobacco products are utilized by inserting some form of processed tobacco or tobacco-containing formulation into the user's mouth. Traditional formats for such smokeless tobacco products include moist snuff, snus, and chewing tobacco, which are typically formed substantially entirely of granulated, granular, or cut tobacco and either divided by the user or provided to the user in individual portions, e.g., disposable pouches or sachets. Other traditional forms of smokeless products include compressed or agglomerated forms, e.g., plugs, tablets, or pellets. Alternative product formats are also known, such as tobacco-containing gums and mixtures of tobacco with other plant materials.See, for example, U.S. Pat. No. 1,376,586 to Schwartz; U.S. Pat. No. 4,513,756 to Pittman et al.; U.S. Pat. No. 4,528,993 to Sensabaugh, Jr. et al.; U.S. Pat. No. 4,624,269 to Story et al.; U.S. Pat. No. 4,991,599 to Tibbetts; U.S. Pat. No. 4,987,907 to Townsend; U.S. Pat. No. 4,987,907 to Sprinkle, III et al., each of which is incorporated herein by reference. No. 5,092,352 to White et al.; U.S. Pat. No. 5,387,416 to White et al.; U.S. Pat. No. 6,668,839 to Williams; U.S. Pat. No. 6,834,654 to Williams; U.S. Pat. No. 6,953,040 to Atchley et al.; U.S. Pat. No. 7,032,601 to Atchley et al.; and U.S. Pat. No. 7,694,686 to Atchley et al.; U.S. Patent Publication No. 2004 / 0020503 to Williams; U.S. Patent Publication No. 2005 / 0115580 to Inter et al.; U.S. Patent Publication No. 2006 / 0191548 to Strickland et al.; U.S. Patent Publication No. 2007 / 0062549 to Holton, Jr. et al.; U.S. Patent Publication No. 2007 / 0186941 to Holton, Jr. et al.; U.S. Patent Publication No. 2007 / 0186942 to Strickland et al.; U.S. Patent Publication No. 2008 / 0029110 to Dube et al.; Robinson et al. See the types of smokeless tobacco formulations, ingredients and processing methods described in U.S. Patent Publication No. 2008 / 0029116; U.S. Patent Publication No. 2008 / 0173317 to Robinson et al.; U.S. Patent Publication No. 2008 / 0209586 to Neilsen et al.; U.S. Patent Publication No. 2009 / 0065013 to Essen et al.; and U.S. Patent Publication No. 2010 / 0282267 to Atchley, as well as WO 2004 / 095959 to Arnarp et al.

[0003] The construction of smokeless tobacco products that combine tobacco materials with a variety of binders and fillers has recently been proposed, with exemplary product formats including lozenges, pastilles, gels, extruded forms, and the like. See, for example, U.S. Patent Application Publication No. 2008 / 0196730 to Engstrom et al.; U.S. Patent Application Publication No. 2008 / 0305216 to Crawford et al.; U.S. Patent Application Publication No. 2009 / 0293889 to Kumar et al.; U.S. Patent Application Publication No. 2010 / 0291245 to Gao et al.; U.S. Patent Application Publication No. 2011 / 0139164 to Mua et al.; U.S. Patent Application Publication No. 2012 / 0037175 to Cantrell et al.; U.S. Patent Application Publication No. 2012 / 0055494 to Hunt et al.; U.S. Patent Application Publication No. 2012 / 0138073 to Cantrell et al.; See the types of products described in U.S. Patent Application Publication No. 2012 / 0138074 to Rell et al.; U.S. Patent Application Publication No. 2013 / 0074855 to Holton, Jr.; U.S. Patent Application Publication No. 2013 / 0074856 to Holton, Jr.; U.S. Patent Application Publication No. 2013 / 0152953 to Mua et al.; U.S. Patent Application Publication No. 2013 / 0274296 to Jackson et al.; U.S. Patent Application Publication No. 2015 / 0068545 to Moldoveanu et al.; U.S. Patent Application Publication No. 2015 / 0101627 to Marshall et al.; and U.S. Patent Application Publication No. 2015 / 0230515 to Lampe et al. [Prior art documents] [Patent documents]

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

[0005] (Brief summary) The present disclosure generally provides a product that is structured for oral use. The product includes one or more fillers and at least one sugar alcohol. The product generally includes at least one flavoring agent, at least one active ingredient, or at least one of both flavoring agent and active ingredient. Surprisingly, according to the present disclosure, it has been found that the presence of certain moistening materials, such as milled non-tobacco botanical materials and extracts, in the product can result in a more uniform product using wet granulation of a dry blend with an aqueous binder solution. In particular, the disclosed method is advantageous when preparing products that include non-tobacco botanical materials and / or flavoring agents that exhibit stickiness or tackiness. The presence of such materials in the product composition makes such mixtures unable to be effectively compressed into tablets, making such compositions difficult to process. The granulation method disclosed herein minimizes potential processing problems, such as poor flowability, lack of uniformity, clumping, etc., and allows the granulated material to be effectively compressed into a given shape, such as pellets or tablets. [Means for solving the problem]

[0006] Thus, in one aspect, the disclosure provides a method of preparing a product structured for oral use, comprising blending at least one filler, at least one sugar alcohol, and an active ingredient, a flavoring agent, or both, to form a dry blend, and granulating a combination of the dry blend with an aqueous binder solution to form a plurality of granules.

[0007] In some embodiments, the dry blend comprises an active ingredient and a flavoring agent. In some embodiments, the dry blend comprises an active ingredient and is substantially free of a flavoring agent.

[0008] In some embodiments, the granules have a size ranging from about 60 μm to 500 μm.

[0009] In some embodiments, the method further comprises compressing the plurality of granules into a predetermined shape, hi some embodiments, the predetermined shape is a pellet or a tablet.

[0010] In some embodiments, the method further comprises mixing the plurality of granules with at least one flavoring agent or flow aid, or both, prior to said compressing step. In some embodiments, the method further comprises mixing the plurality of granules with at least one flavoring agent and flow aid, prior to said compressing step. In some embodiments, the flow aid is selected from the group consisting of microcrystalline cellulose, silica, polyethylene glycol, stearic acid, calcium stearate, magnesium stearate, zinc stearate, sodium stearyl fumarate, canauba wax, and combinations thereof.

[0011] In some embodiments, the method further comprises applying a coating composition to the product. In some embodiments, the coating composition comprises a cellulosic material. In some embodiments, the coating composition comprises a flavoring agent.

[0012] In some embodiments, the at least one filler comprises calcium carbonate, microcrystalline cellulose, maltodextrin, rice starch, or combinations thereof.

[0013] In some embodiments, the aqueous binder solution comprises a binder selected from the group consisting of methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, polyvinylpyrrolidone, and combinations thereof. In some embodiments, the aqueous binder solution comprises polyvinylpyrrolidone.

[0014] In some embodiments, the at least one sugar alcohol is selected from the group consisting of erythritol, isomalt, maltitol, mannitol, sorbitol, and combinations thereof, hi some embodiments, the at least one sugar alcohol is mannitol.

[0015] In some embodiments, the active ingredient is selected from the group consisting of a nicotine component, a botanical material, a nutraceutical, a stimulant, an amino acid, a vitamin, and a cannabinoid. In some embodiments, the active ingredient is a non-tobacco botanical material. In some embodiments, the non-tobacco botanical material is in milled form or in the form of an extract.

[0016] In some embodiments, products constructed for oral use contain from about 0.001 to about 10% by weight of a nicotine component, calculated as the free base, based on the total dry weight of the composition.

[0017] In some embodiments, products constructed for oral use are substantially free of tobacco materials, except for any nicotine components present.

[0018] In some embodiments, the method further comprises adding one or more of a salt, a sweetener, a buffering agent, a coloring agent, a humectant, an oral care additive, a preservative, a disintegration aid, a flow aid, a compression aid, or a combination thereof to the dry blend, the aqueous binder solution, or both.

[0019] In another aspect, there is provided a product constructed for oral use comprising a plurality of granules, the granules comprising at least one filler; at least one sugar alcohol; a cellulose ether, a polyvinylpyrrolidone, or a combination thereof; and an active ingredient, a flavoring agent, or both.

[0020] In some embodiments, the at least one filler comprises a filler selected from the group consisting of calcium carbonate, microcrystalline cellulose, maltodextrin, rice starch, and combinations thereof, the at least one sugar alcohol comprises mannitol, and the at least one active ingredient is a milled non-tobacco botanical material.

[0021] In some embodiments, the product is in the form of a compressed pellet or tablet having an outer surface and further comprises a coating on said outer surface, the coating comprising a flavoring agent.

[0022] The present disclosure includes, without limitation, the following embodiments.

[0023] Embodiment 1: A method of preparing a product structured for oral use, comprising blending at least one filler, at least one sugar alcohol, and an active ingredient, a flavoring agent, or both, to form a dry blend, and granulating a combination of the dry blend with an aqueous binder solution to form a plurality of granules.

[0024] Embodiment 2: The method of embodiment 1, wherein the dry blend comprises an active ingredient and a flavoring agent.

[0025] Embodiment 3: The method of embodiment 1, wherein the dry blend comprises an active ingredient and is substantially free of flavoring agents.

[0026] Embodiment 4: The method of any one of embodiments 1 to 3, wherein the granules have a size in the range of about 60 μm to 500 μm.

[0027] Embodiment 5: The method of any one of embodiments 1-4, further comprising compressing the plurality of granules into a predetermined shape.

[0028] Embodiment 6: The method of any one of embodiments 1 to 5, wherein the predetermined shape is a pellet or a tablet.

[0029] Embodiment 7: The method of any one of embodiments 1-6, further comprising mixing the plurality of granules with at least one flavoring agent or flow aid, or both, prior to said compressing step.

[0030] Embodiment 8: The method of any one of embodiments 1-7, further comprising mixing the plurality of granules with at least one flavoring agent and flow aid prior to said compressing step.

[0031] Embodiment 9: The method of any one of embodiments 1-8, wherein the flow aid is selected from the group consisting of microcrystalline cellulose, silica, polyethylene glycol, stearic acid, calcium stearate, magnesium stearate, zinc stearate, sodium stearyl fumarate, carnauba wax, and combinations thereof.

[0032] Embodiment 10: The method of any one of embodiments 1-9, further comprising applying a coating composition to the product.

[0033] Embodiment 11: The method of any one of embodiments 1-10, wherein the coating composition comprises a cellulosic material.

[0034] Embodiment 12: The method of any one of embodiments 1-11, wherein the coating composition comprises a flavoring agent.

[0035] Embodiment 13: The method of any one of embodiments 1-12, wherein the at least one filler comprises calcium carbonate, microcrystalline cellulose, maltodextrin, rice starch, or a combination thereof.

[0036] Embodiment 14: The method of any one of embodiments 1 to 13, wherein the aqueous binder solution comprises a binder selected from the group consisting of methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, polyvinylpyrrolidone, and combinations thereof.

[0037] Embodiment 15: The method of any one of embodiments 1 to 14, wherein the aqueous binder solution comprises polyvinylpyrrolidone.

[0038] Embodiment 16: The method of any one of embodiments 1 to 15, wherein the at least one sugar alcohol is selected from the group consisting of erythritol, isomalt, maltitol, mannitol, sorbitol, and combinations thereof.

[0039] Embodiment 17: The method of any one of embodiments 1 to 16, wherein the at least one sugar alcohol is mannitol.

[0040] Embodiment 18: The method of any one of embodiments 1 to 17, wherein the active ingredient is selected from the group consisting of nicotine components, botanical materials, nutraceuticals, stimulants, amino acids, vitamins, cannabinoids, cannabimetics, terpenes, and combinations thereof.

[0041] Embodiment 19: The method of any one of embodiments 1-18, wherein the active ingredient is a non-tobacco botanical material.

[0042] Embodiment 20: The method of any one of embodiments 1-19, wherein the non-tobacco botanical material is in milled form or in the form of an extract.

[0043] Embodiment 21: The method of any one of embodiments 1 to 20, wherein the product constructed for oral use comprises from about 0.001 to about 10% by weight of a nicotine component, calculated as the free base, based on the total dry weight of the composition.

[0044] Embodiment 22: The method of any one of embodiments 1 to 21, wherein the product constructed for oral use is substantially free of tobacco materials, except for any nicotine components present.

[0045] Embodiment 23: The method of any one of embodiments 1 to 22, further comprising the step of adding one or more of a salt, a sweetener, a buffering agent, a coloring agent, a humectant, an oral care additive, a preservative, a disintegration aid, a flow aid, a compression aid, or a combination thereof to the dry blend, the aqueous binder solution, or both.

[0046] Embodiment 24: A product constructed for oral use comprising a plurality of granules, the granules comprising at least one filler; a cellulose ether, a polyvinylpyrrolidone, or a combination thereof; at least one sugar alcohol; and an active ingredient, a flavoring agent, or both.

[0047] Embodiment 25: The product of embodiment 24, wherein the at least one filler comprises a filler selected from the group consisting of calcium carbonate, microcrystalline cellulose, maltodextrin, rice starch, and combinations thereof, the at least one sugar alcohol comprises mannitol, and the at least one active ingredient is a milled non-tobacco botanical material.

[0048] Embodiment 26: The product of embodiment 25, wherein the product is in the form of a compressed pellet or tablet having an outer surface and further comprises a coating on said outer surface, the coating comprising a flavoring agent.

[0049] These and other features, aspects and advantages of the present disclosure will become apparent upon reading the following detailed description in conjunction with the accompanying figures, which are briefly described below. The present invention includes any combination of two, three, four or more of the above-described embodiments, as well as any combination of two, three, four or more features or elements described in this disclosure, regardless of whether such features or elements are explicitly combined in the description of a particular embodiment herein. Because this disclosure is intended to be read as a whole, it should be considered that any separable features or elements of the disclosed invention are intended to be combinable in any of its various aspects and embodiments, unless the context clearly dictates otherwise.

[0050] Having described the foregoing aspects of the disclosure in general terms, reference will now be made to the accompanying drawings, which are not necessarily drawn to scale, and which are merely examples and should not be construed as limiting the disclosure. [Brief description of the drawings]

[0051] [Figure 1] FIG. 1 is a perspective view of an exemplary embodiment of a product of the present disclosure. [Diagram 2] FIG. 2 is a perspective view of another exemplary embodiment of a product of the present disclosure in the form of a tablet having a width, length and thickness. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0052] The present disclosure generally provides a method of preparing a product structured for oral use, the method including blending at least one filler, at least one sugar alcohol, and an active ingredient, a flavoring agent, or both, to form a dry blend, and granulating a combination of the dry blend with an aqueous binder solution to form a plurality of granules.

[0053] Surprisingly, according to the present disclosure, in the preparation of products designed for oral use that contain certain wet materials, such as milled non-tobacco botanical materials or extracts and / or flavorings, and that exhibit stickiness or tackiness, the use of wet granulation of dry blends with aqueous binder solutions results in more uniform products. Otherwise, the presence of such sticky materials in the product composition makes it difficult to process and cannot be effectively compressed into tablets. In particular, the present method is advantageous for the preparation of products that contain non-tobacco botanical materials. The granulation method disclosed herein minimizes potential processing problems, such as poor flowability, lack of uniformity, clumping, etc.

[0054] 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. As used in this specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. References to "percent dry weight" 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 product including water. References to "percent weight" of a product reflect the total wet weight of the product (i.e., including water), unless otherwise indicated.

[0055] oral products The product constructed for oral use described herein comprises one or more fillers; cellulose ether, polyvinylpyrrolidone or combinations thereof; at least one sugar alcohol; and at least one flavoring agent, at least one active ingredient, or both.The relative amounts of various ingredients in the product may vary and are usually selected to provide the product with desired sensory and performance characteristics.Exemplary individual ingredients of the product are described herein below.

[0056] Filler The products described herein include at least one or more fillers. Fillers can fulfill multiple functions, such as enhancing certain organoleptic properties, such as texture and mouthfeel, enhancing the cohesiveness or compressibility of the product, etc. Non-limiting examples of suitable fillers include, but are not limited to, alginates, seaweed hydrocolloids, cellulosic materials including cellulose ethers, starches, gums, dextran, carrageenan, pullulan, zein, and combinations thereof. In general, fillers are porous granular materials, often cellulose-based. For example, suitable fillers are any non-tobacco plant material or derivatives thereof, including cellulosic materials from such sources. Examples of cellulosic non-tobacco plant materials include grains (e.g., corn, oats, barley, rye, buckwheat, etc.), sugar beets (e.g., FIBREX® brand fillers available from International fiber Corporation), bran fibers, and mixtures thereof. Non-limiting examples of derivatives of non-tobacco plant materials include starches (eg, from potato, bamboo, wheat, rice, corn), natural cellulose and modified cellulosic materials.

[0057] "Starch" as used herein can refer to pure starch, modified starch, or starch derivatives from any source. Starch is usually present in granular form in almost all green plants and in various types of plant tissues and organs (e.g., seeds, leaves, rhizomes, roots, tubers, shoots, fruits, grains, and stems). Starch may vary in composition and granule shape and size. Often, starches from different sources have different chemical and physical characteristics. A particular starch may be selected for inclusion in a product based on the ability of the starch material to impart certain organoleptic properties to the product. Starch from various sources may be used. For example, major sources of starch include cereals (e.g., rice, wheat, and corn) and root vegetables (e.g., potato and cassava). Other examples of starch sources include acorn, arrowroot, arracachá, banana, barley, legumes (e.g., broad bean, lentil, mung bean, pea, chickpea), breadfruit, buckwheat, canna, chestnut, colocasia, dogtooth violet, kudzu, malanga, millet, oat, oka, Polynesian arrowroot, sago, sorghum, sweet potato, quinoa, rye, tapioca, taro, tobacco, water chestnut, and yam. Certain starches are modified starches. Modified starches have undergone one or more structural changes, often designed to alter their high thermal properties. Some starches have been developed by genetic engineering and are considered "modified" starches. Other starches are obtained and subsequently modified. For example, modified starches can be starches that have been subjected to chemical reactions, such as esterification, etherification, oxidation, depolymerization (thinning) by acid catalysis or oxidation in the presence of a base, bleaching, transglycosylation and depolymerization (e.g., dextrinization in the presence of a catalyst), crosslinking, enzyme treatment, acetylation, hydroxypropylation, and / or partial hydrolysis. Other starches are modified by heat treatment, such as pregelatinization, dextrinization, and / or cold water swelling processes.Certain modified starches include phosphorylated starch, glycerol cross-linked starch, phosphate cross-linked starch esterified with sodium trimetaphosphate, phosphorylated phosphate cross-linked starch, acetylated phosphate cross-linked starch, starch acetate esterified with acetic anhydride, starch acetate esterified with vinyl acetate, acetylated adipate cross-linked starch, acetylated glycerol cross-linked starch, hydroxypropylated starch, hydroxypropylated glycerol cross-linked starch, and sodium starch octenyl succinate. In some embodiments, the filler comprises rice starch.

[0058] In some embodiments, the filler comprises a cellulose material. One particularly suitable filler for use in the products described herein is microcrystalline cellulose ("mcc"). MCC can be synthetic, semi-synthetic, or derived entirely from natural cellulose. MCC can be selected from the group consisting of AVICEL® grades PH-100, PH-102, PH-103, PH-105, PH-112, PH-113, PH-200, PH-300, PH-302, VIVACEL® grades 101, 102, 12, 20, and EMOCEL® grades 50M and 90M, and the like, and mixtures thereof. In some embodiments, the products comprise mcc. The amount of mcc present in the products described herein can vary depending on the desired properties.

[0059] In some embodiments, the filler comprises cellulose derivatives, such as cellulose ethers (including carboxyalkyl ethers), which refers to cellulose polymers in which the hydrogen of one or more hydroxyl groups in the cellulose structure is replaced by an alkyl group, a hydroxyalkyl group, or an aryl group.Non-limiting examples of such cellulose derivatives include methylcellulose, hydroxypropylcellulose ("HPC"), hydroxypropylmethylcellulose ("HPMC"), hydroxyethylcellulose, and carboxymethylcellulose ("CMC").Suitable cellulose ethers include hydroxypropylcellulose, such as Klucel H from Aqualon Co.; hydroxypropylmethylcellulose, such as Methocel K4MS from DuPont; hydroxyethylcellulose, such as Natrosol250 MRCS from Aqualon Co.; methylcellulose, such as Methocel A4M, K4M, and E15 from DuPont; and sodium carboxymethylcellulose, such as CMC 7HF, CMC 7LF, and CMC 7H4F from Aqualon Co. In some embodiments, the at least one filler is one or more cellulose ethers (e.g., a single cellulose ether or a combination of several cellulose ethers, e.g., two or three). In some embodiments, the filler is a cellulose ether selected from the group consisting of methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, and combinations thereof. In some embodiments, the at least one filler is carboxymethylcellulose.

[0060] Other suitable fillers include gums, such as natural gums. As used herein, natural gums refer to polysaccharide materials of natural origin that have binding properties and are also useful as thickeners or gelling agents. Representative natural gums derived from plants, which are usually water-soluble to some extent, include xanthan gum, guar gum, gum arabic, gum ghatti, gum tragacanth, gum karaya, locust bean gum, gellan gum, and combinations thereof.

[0061] Additional examples of potential fillers include maltodextrin, dextrose, calcium carbonate, calcium phosphate, lactose, mannitol, xylitol, and sorbitol. In some embodiments, the filler comprises calcium carbonate. In some embodiments, the filler comprises maltodextrin.

[0062] Combinations of fillers may also be used, hi some embodiments, the filler is a combination of calcium carbonate, maltodextrin, microcrystalline cellulose and rice starch.

[0063] The amount of filler may vary, but is typically up to about 40 percent of the product by weight, based on the total weight of the product. A typical range of filler in a product can be from about 10 to about 40 percent, e.g., from about 10, about 15, about 20, or about 25, to about 30, about 35, or about 40 percent by weight (e.g., about 20 to about 40 percent by weight or about 25 to about 35 percent by weight), based on the total weight of the product. In certain embodiments, the amount of filler is at least about 10 percent by weight, e.g., at least about 15 percent, at least about 20 percent, at least about 25 percent, at least about 30 percent, or at least about 35 percent, based on the total weight of the product. In embodiments where the product includes more than one filler, it should be understood that the stated weight basis of the filler reflects the total weight of the combination of fillers, based on the total wet weight of the product.

[0064] Sugar alcohols The products described herein include at least one sugar alcohol. Sugar alcohols are polyols derived from mono- or disaccharides, with partial or complete hydrogenation. Sugar alcohols, for example, have from about 4 to about 20 carbon atoms and include erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and combinations thereof (e.g., hydrogenated starch hydrolysates). Isomalt is an equimolar mixture of two disaccharides, each of which consists 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 at least one sugar alcohol is selected from the group consisting of erythritol, isomalt, maltitol, mannitol, sorbitol, and combinations thereof.

[0065] In some embodiments, the at least one sugar alcohol comprises isomalt. In some embodiments, the at least one sugar alcohol is isomalt. In some embodiments, the at least one sugar alcohol comprises or is maltitol. In some embodiments, the at least one sugar alcohol comprises mannitol.

[0066] In some embodiments, the at least one sugar alcohol is a combination of two or even three sugar alcohols. In some embodiments, the at least one sugar alcohol comprises or is a mixture of glucose and starch-derived polysaccharides. One such suitable mixture of glucose and starch-derived polysaccharides is EMDEX®, available from JRS PHARMA LP, 2981 Route 22, Patterson, NY12563-2359, USA. In some embodiments, the at least one sugar alcohol comprises a combination of isomalt and EMDEX®. In some embodiments, the at least one sugar alcohol is a combination of isomalt and EMDEX®. In some embodiments, the at least one sugar alcohol is a combination of isomalt and maltitol.

[0067] The total amount of sugar alcohol can vary, but is typically greater than about 5% and up to about 30% by weight of the product, based on the total weight of the product. Typical ranges of sugar alcohol in the product can be, for example, from about 5, about 10, or about 15, up to about 20, about 25, or about 30% by weight.

[0068] water The water content of the product may vary depending on the desired properties prior to use by the user of the product. Typically, the product will be less than about 15% water by weight, generally about 0.1 to about 10% water by weight, for example about 0.1 to about 1, about 1 to about 10, or about 1 to about 5% water by weight based on the total weight of the product.

[0069] active ingredient The products disclosed herein, in certain embodiments, include an active ingredient. As used herein, "active ingredient" refers to one or more substances that belong to any of the following categories: API (active pharmaceutical ingredient), 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 are sometimes defined in the art to include substances commonly available from natural sources (e.g., botanical materials) that provide one or more beneficial biological effects (e.g., health promotion, disease prevention, or other pharmacological effects) but that are not classified or regulated as drugs.

[0070] Non-limiting examples of active ingredients include those that fall into the categories of botanical ingredients (e.g., hemp, lavender, peppermint, eucalyptus, rooibos, fennel, clove, chamomile, basil, rosemary, clove, citrus, ginger, hemp, carrot, maca, and herbal teas), stimulants (e.g., caffeine or guarana), amino acids (e.g., taurine, theanine, phenylalanine, tyrosine, and tryptophan), vitamins (e.g., B6, B12, and C), antioxidants, nicotine ingredients, pharmaceutical ingredients (e.g., nutraceutical and medicinal ingredients), cannabinoids (e.g., tetrahydrocannabinol (THC) or cannabidiol (CBD)), and / or melatonin. 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 product.

[0071] Additionally, any of the above types of active ingredients may be encapsulated in the composition, in the final product, or both to avoid chemical degradation of these actives or to reduce strong taste, including, but not limited to, caffeine, vitamin A, and iron (Fe). Additionally, these encapsulated actives may have to be paired with excipients in the composition to increase their solubility and / or bioavailability. Non-limiting examples of these excipients include beta-carotene, lycopene, vitamin D, vitamin E, coenzyme Q10, vitamin K, and curcumin.

[0072] The specific percentage of active ingredients present will vary depending on the desired characteristics of the particular product. Typically, the active ingredient or combination thereof is present at a total concentration of at least about 0.001% by weight of the product, for example, in the range of about 0.001% to about 20% by weight. In some embodiments, the active ingredient or combination of active ingredients is present at a concentration of about 0.1% w / w to about 10% by weight, for example, about 0.5% w / w to about 10% by weight, about 1% to about 10% by weight, or about 1% to about 5% by weight, based on the total weight of the product. In some embodiments, the active ingredient or combination of active ingredients may be present in an amount ranging 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 0.009%, 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.

[0073] Botanical In some embodiments, the active ingredient comprises a botanical ingredient. As used herein, the term "botanical ingredient" or "botanical" refers to any plant material or fungus-derived material (including plant material in its natural form) and plant material derived from natural plant material, such as an extract or isolate from a plant material or a processed plant material (e.g., a plant material that has been subjected to a heat treatment, fermentation, bleaching, or other treatment process that can modify the physical and / or chemical properties of the material). For purposes of this disclosure, "botanical" includes, but is not limited to, "herbal materials," which refer to seed-producing plants that do not produce persistent woody tissue and are often valued for their medicinal or sensory properties (e.g., tea or herbal tea). In some embodiments, the active ingredient comprises a non-tobacco botanical material. When referring to "non-tobacco" and botanical materials, it is intended to exclude tobacco materials (i.e., not including any Nicotiana species). When present, botanicals (e.g., non-tobacco botanical materials) are typically present at a concentration of about 0.01% w / w to about 10% by weight, e.g., from about 0.01% w / w, about 0.05% w / w, about 0.1% w / w, or about 0.5% w / w, to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%, about 11%, about 12%, about 13%, about 14%, or about 15% by weight, based on the total weight of the composition. Botanical (e.g., non-tobacco botanical) materials useful in the present disclosure can include any of the compounds and sources described herein, including, without limitation, mixtures thereof. Certain non-tobacco 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 medicine, either as botanical ingredients or as botanical extracts, and are further described herein.Non-limiting examples of plants or plant-derived materials include ashwagandha, Bacopa monniera, baobab, basil, Centella asiatica, chai fu, chamomile, cherry blossom, chlorophyll, cinnamon, citrus, clove, cocoa, cordyceps, curcumin, damiana, Dorstenia arifolia, Dorstenia odorata, essential oils, eucalyptus, fennel, Galphimia glauca, ginger, Ginkgo biloba, carrots (e.g., Panax ginseng), green tea, Griffonia simplicifolia, and the like. simplicifolia, Guarana, Cannabis, Hops, Jasmine, Kaempferia parviflora (Turmeric), Kava, Lavender, Lemon Balm, Lemongrass, Licorice, Lutein, Maca, Matcha, Oil-based Extract of Nardostachys chinensis, Viola odorata, Peppermint, Quercetin, Resveratrol, Rhizoma gastrodiae, Rhodiola, Rooibos, Rose Essential Oil, Rosemary, Sceletium tortuosum, Schisandra chinensis, Skullcap, Spearmint Extract, Spikenard, Terpenes, Herbal Tea, Turmeric, Turnera aphrodisiaca aphrodisiaca, valerian, mulberry, and yerba mate. In some embodiments, the botanical material is present in an encapsulated form.

[0074] In some embodiments, the non-tobacco botanical material is present in a milled form. The milled form of the non-tobacco botanical material can have a range of particle sizes. For example, in some embodiments, the milled non-tobacco botanical material has a particle size of about 0.05 mm to about 1 mm. In some cases, the non-tobacco botanical material particles can be sized to pass through a screen mesh to obtain the required particle size range.

[0075] In some embodiments, the non-tobacco botanical material is present in the form of an extract. "Botanical extract," as used herein, refers to an isolated component of a non-tobacco botanical material that is extracted from a solid botanical material by a solvent (e.g., water, alcohol, etc.) that is contacted with the solid botanical material in an extraction process. A variety of extraction techniques for solid botanical materials can be used to obtain a botanical material extract.

[0076] In some embodiments, the non-tobacco botanical material comprises lemon balm. Lemon balm (Melissa officinalis) is a mild lemon-scented herb from the same family as mint (Lamiaceae). The herb is native to Europe, North Africa and Western Asia. Lemon balm teas, as well as essential oils and extracts, are used in traditional and alternative medicines. In some embodiments, the non-tobacco botanical material comprises lemon balm extract. In some embodiments, the lemon balm extract is present in an amount of about 1 to about 4% by weight, based on the total weight of the product.

[0077] In some embodiments, the non-tobacco botanical material comprises ginseng. Ginseng is the root of the Panax plant and is characterized by the presence of unique steroidal saponin phytochemical agents (ginsenosides) and gintonin. Ginseng finds use as a dietary supplement in energy drinks or herbal teas and traditional medicines. Cultivated species include P. ginseng (P. Ginseng), P. notoginseng (P. notoginseng) and P. quinquefolius (P. quinquefolius). American ginseng and P. ginseng differ in the types and amounts of various ginsenosides present. In some embodiments, the ginseng is American ginseng or P. ginseng. In certain embodiments, the non-tobacco botanical material comprises P. ginseng. In some embodiments, the ginseng is present in an amount of about 0.4 to about 0.6% by weight based on the total weight of the product.

[0078] 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.

[0079] In some embodiments, the active ingredient comprises caffeine. In some embodiments, the active ingredient comprises theacrine. In some embodiments, the active ingredient comprises a combination of caffeine and theacrine. In some embodiments, the active ingredient is caffeine. In some embodiments, the caffeine is present in encapsulated form. One example of encapsulated caffeine is Vitashure® available from Balchem ​​Corp., 52 Sunrise Park Road, New Hampton, NY, 10958.

[0080] When present, the stimulant or combination of stimulants (e.g., caffeine, theacrine, and combinations thereof) are typically at a concentration of about 0.1% w / w to about 15% by weight, for example, from about 0.1% w / w, about 0.2% w / w, about 0.3% w / w, about 0.4% w / w, about 0.5% w / w, about 0.6% w / w, about 0.7% w / w, about 0.8% w / w, or about 0.9% w / w, to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, or about 15% by weight, based on the total weight of the product.

[0081] 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 "Proteinogenic" refers to an organic compound that contains a functional group, a carboxyl group, with a side chain (R group), which is specific for each amino acid. Amino acids may be proteinogenic or non-proteinogenic. "Proteinogenic" 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., it is a product of post-translational modifications). 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.

[0082] In some embodiments, the amino acid is taurine, theanine, phenylalanine, tyrosine, tryptophan, or a combination thereof. In some embodiments, the amino acid is taurine. In some embodiments, the active ingredient comprises a combination of taurine and caffeine. In some embodiments, the active ingredient comprises a combination of taurine, caffeine, and guarana. In some embodiments, the active ingredient comprises a combination of taurine, maca, and cordyceps. In some embodiments, the active ingredient comprises a combination of theanine and caffeine. In some embodiments, the active ingredient comprises a combination of theanine and GABA. In some embodiments, the active ingredient comprises theanine in an amount of about 5 to about 10% by weight, and GABA in an amount of about 5 to about 10% by weight, based on the total weight of the product. In some embodiments, the active ingredient comprises a combination of theanine, GABA, and lemon balm. In some embodiments, the active ingredient comprises a combination of caffeine, taurine, and vitamin C. In some embodiments, the active ingredient is a combination of caffeine, theanine, and ginseng. In some embodiments, the active ingredient comprises taurine.

[0083] 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 product.

[0084] 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).

[0085] If present, a 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 product.

[0086] In some embodiments, the vitamin is vitamin B6, vitamin B12, vitamin E, vitamin C, or a combination thereof. In some embodiments, the active ingredient comprises a combination of vitamin B6, caffeine, and theanine. In some embodiments, the active ingredient comprises vitamin B6, vitamin B12, and taurine. In some embodiments, the active ingredient comprises a combination of vitamin B6, vitamin B12, carrot, and theanine. In some embodiments, the active ingredient comprises a combination of vitamin C, baobab, and chlorophyll.

[0087] In some embodiments, the active ingredient comprises Vitamin A. In some embodiments, the Vitamin A is encapsulated.

[0088] 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.

[0089] In some embodiments, the active ingredients described herein may be susceptible to degradation (e.g., oxidative, photolytic, thermal, volatilizing) during processing or storage of the oral product. In such embodiments, the active ingredients (e.g., caffeine, vitamin A, and iron (Fe)) may be encapsulated or the matrix may be modified, particularly with fillers, binders, etc., to provide the active ingredients with enhanced stability. For example, binders, such as functional celluloses (e.g., cellulose ethers, including but not limited to, hydroxypropyl cellulose), may be used to enhance the stability of such actives against degradation. 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.

[0090] 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.

[0091] 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 / herbal materials. Non-limiting examples of antioxidants include certain botanical / herbal materials, vitamins, polyphenols, and phenol derivatives.

[0092] Examples of botanical / herbal 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, hibiscus. These include: gusto flower, gynostemma, kava, lavender, licorice, origanum, milk thistle, mint (mantle), 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 herbal materials may be provided in fresh or dried form, in essential oils, or in the form of extracts. Herbal materials (as well as their extracts) often contain various classes of compounds known to provide antioxidant effects, 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, which is incorporated herein by reference.

[0093] Other suitable antioxidants include, but are not limited to, 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. In some embodiments, the antioxidant is vitamin E or a derivative thereof, a flavonoid, a polyphenol, a carotenoid, or a combination thereof.

[0094] When present, antioxidants are typically at a concentration of about 0.001% w / w to about 10% by weight, e.g., 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 product.

[0095] 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).

[0096] 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), thrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabinotriol (CBO), tetrahydrocannabinolic acid (THCA), 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. Notably, CBD has a logP value of about 6.5, which makes it insoluble in an aqueous environment (e.g., saliva).

[0097] In some embodiments, the cannabinoid (e.g., CBD) is added to the oral product 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.

[0098] In some embodiments, the cannabinoid is an isolate of CBD at a high degree of purity and the amount of any other cannabinoids in the oral product is about 1% or less by weight of the oral product, such as about 0.5% or less by weight of the oral product, such as about 0.1% or less by weight of the oral product, for example about 0.01% or less by weight of the oral product.

[0099] The selection of cannabinoids and the specific percentages that may be present in the disclosed oral products will vary depending on the desired flavor, texture, and other characteristics of the oral product.

[0100] 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 oral product, for example, in the range of about 0.001% to about 2% by weight of the oral product. 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.

[0101] Alternatively, or in addition to cannabinoids, the active ingredient may include cannabimetics. This is a class of compounds derived from plants other than cannabis that have biological effects on the endocannabinoid system similar to cannabinoids. Examples include yangonin, alpha-amyrin or beta-amyrin (also classified as terpenes), cyanidin, curcumin (turmeric), catechin, quercetin, salvinorin A, N-acylethanolamines, and N-alkylamide lipids. Such compounds may be used in the same amounts and in the same ratios as specified herein for cannabinoids.

[0102] 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 cannabimetics. 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.

[0103] 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.

[0104] 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.

[0105] The amount of API, if present, may vary. For example, the API, if present, is typically present in an amount of from about 0.001% w / w to about 10% by weight, e.g., 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 product. / 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%.

[0106] In some embodiments, the composition is substantially free of any API. "Substantially free of any API" means that the composition does not contain, and specifically excludes, any presence of any API as defined herein, such as any Food and Drug Administration (FDA) approved therapeutic agent intended to treat any medical condition.

[0107] Nicotine content In certain embodiments, the active ingredient comprises a nicotine component. By "nicotine component" is meant nicotine in any suitable form (e.g., free base or salt) to provide for oral absorption of at least a portion of the nicotine present.

[0108] The nicotine source may be varied, natural or synthetic. Most preferably, the nicotine is natural and obtained as an extract from Nicotiana species (e.g., tobacco). The nicotine may have the enantiomeric forms S(-)-nicotine, R(+)-nicotine, or a mixture of S(-)-nicotine and R(+)-nicotine. Most preferably, the nicotine is in the form of S(-)-nicotine (e.g., a form that is substantially all S(-)-nicotine) or a racemic mixture composed primarily or mostly 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, by weight.

[0109] 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.

[0110] 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. In some embodiments, the nicotine component includes or is nicotine benzoate.

[0111] In some embodiments, at least a portion of the nicotine can be in the form of a resin complex of nicotine, such as nicotine polacrilex, in which nicotine is bound to an ion exchange resin. This is, for example, nicotine bound to polymethacrylic acid, such as Amberlite IRP64, Purolite C115HMR, or Doshion P551. See 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, nicotine can be in the form of a nicotine polyacryl complex. In some embodiments, the composition includes nicotine polacrilex.

[0112] In some embodiments, the only nicotine present in the composition is added in the form of resin-bound nicotine (e.g., nicotine polacrilex). In some embodiments, the composition comprises resin-bound nicotine (e.g., nicotine polacrilex) and further comprises free base nicotine, a nicotine salt, ion-paired nicotine, or a combination thereof. In some embodiments, at least a portion of the nicotine present in the composition is present as an ion pair, as further described herein below.

[0113] Typically, the nicotine component (calculated as the free base), when present, is at a concentration of at least about 0.001% by weight of the product, e.g., in the range of about 0.001% to about 10%. In some embodiments, the nicotine component, calculated as the free base, is present in a concentration of about 0.1% w / w to about 10% by weight, e.g., 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% by weight, 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 product. 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 product, e.g., about 0.1% w / w to about 2.5% by weight, about 0.1% to about 2.0% by weight, about 0.1% to about 1.5% by weight, or about 0.1% 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 resin-bound nicotine (e.g., nicotine polacrilex).

[0114] In some embodiments, the product or products 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" it is meant that no nicotine has been intentionally added, e.g., beyond trace amounts that may be naturally present in 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.

[0115] In some embodiments, the active ingredient comprises a nicotine component (e.g., any of the products of the present disclosure can further comprise a nicotine component in addition to comprising any active ingredient or combination of active ingredients disclosed herein). In some embodiments, the active ingredient comprises a combination of nicotine and ginseng. In some embodiments, the active ingredient comprises a combination of nicotine and caffeine. In some embodiments, the active ingredient comprises a combination of nicotine and guarana.

[0116] 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 oral product. In such embodiments, the active ingredients (e.g., caffeine, vitamin A, and iron (Fe)) may be encapsulated or the matrix may be otherwise modified with fillers, binders, etc. to provide enhanced stability to the active ingredients. For example, binders, such as functional celluloses (e.g., cellulose ethers, including but not limited to hydroxypropyl cellulose), may be used to enhance the stability of such actives against degradation. 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.

[0117] 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.

[0118] 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 oral product, 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.

[0119] 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, are responsible for the color of the active ingredient and 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, based on 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 are responsible for the visible color of the active ingredient.

[0120] 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.

[0121] 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.

[0122] 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.

[0123] 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.

[0124] 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 handheld colorimeter, in comparison 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). Discoloration 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 handheld instrument.

[0125] Flavoring Agent In some embodiments, the products described herein include flavoring agents. As used herein, "flavoring agent" or "flavoring agent" is any flavorful or fragrant substance that can modify the sensory properties associated with an oral product. Examples of sensory properties that can be modified with flavoring agents include taste, mouthfeel, moistness, cool / heat, and / or flavor / aroma. Flavoring agents can be natural or synthetic, and the resulting flavor properties can be described, without limitation, as fresh, sweet, herbal, confectionery, floral, fruity, or spicy. Specific types of flavorings include, but are not limited to, vanilla, coffee, chocolate / cocoa, cream, mint, spearmint, menthol, peppermint, wintergreen, eucalyptus, lavender, cardamom, nutmeg, cinnamon, clove, cascarilla, sandalwood, honey, jasmine, ginger, anise, sage, licorice, lemon, orange, apple, peach, lime, cherry, strawberry, pineapple, and any combination thereof. See also Leffingwell et al., Tobacco Flavoring for Smoking Products, RJ Reynolds Tobacco Company (1972), which is incorporated herein by reference. Flavorings can also include components that are considered to be humectants, coolants, or smoothing agents, such as eucalyptus. These flavorings may be provided pure (i.e., alone) or in complexes and may be utilized as concentrates or flavoring packages (e.g., spearmint and menthol, orange and cinnamon; lime, pineapple, etc.). Representative types of components are also described in U.S. Patent No. 5,387,416 to White et al., U.S. Patent Application Publication No. 2005 / 0244521 to Strickland et al., and PCT Application No. WO 05 / 041699 to Quinter et al., each of which is incorporated herein by reference. In some cases, the flavoring agent may be provided in a spray-dried or liquid form.

[0126] The amount of flavoring utilized in the product may vary, but will typically be up to about 10 weight percent, with certain embodiments being characterized by a flavoring content of at least about 0.1 weight percent, e.g., from about 0.5 to about 10 weight percent, from about 1 to about 5 weight percent, or from about 2 to about 4 weight percent, based on the total weight of the product.

[0127] Sweetener To improve the sensory properties of the product according to the present disclosure, one or more sweeteners may be added. The sweetener can be any sweetener or combination of sweeteners, in natural or artificial form, or a combination of natural and artificial sweeteners. Examples of natural sweeteners include fructose, sucrose, glucose, maltose, mannose, galactose, lactose, stevia, honey, etc. Examples of artificial sweeteners include sucralose, isomaltulose, maltodextrin, saccharin, aspartame, acesulfame K, neotame, etc. In some embodiments, the sweetener includes sucralose, acesulfame K, or a combination thereof. In some embodiments, the sweetener is sucralose.

[0128] When present, the sweetener or combination of sweeteners may comprise from about 0.01 to about 20% or more by weight of the product, for example, from about 0.01 to about 0.1%, from about 0.1 to about 1%, from about 1 to about 5%, from about 5 to about 10%, or from about 10 to about 20% by weight of the total weight of the product. In some embodiments, the sweetener or combination of sweeteners is present in a concentration of from about 0.01% to about 0.1% by weight of the product, for example, about 0.01, about 0.02, about 0.03, about 0.04, about 0.05, about 0.06, about 0.07, about 0.08, about 0.09, or about 0.1% by weight of the product. In some embodiments, the sweetener or combination of sweeteners is present in a concentration of about 0.1% to about 0.5% by weight of the product, for example, about 0.1, about 0.2, about 0.3, about 0.4 or about 0.5% by weight of the product. In some embodiments, the sweetener or combination of sweeteners is present in a concentration of about 0.5% to about 3% by weight of the product, for example, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1, about 2 or about 3% by weight of the product, based on the total weight of the product.

[0129] salt In some embodiments, the product includes a salt (e.g., an alkali metal salt) that is typically utilized in an amount sufficient to provide the product with the desired sensory attributes. In some embodiments, certain salts can also act as electrolytes or work synergistically with electrolytes. For example, without wishing to be bound by theory, sodium citrate can provide both a source of sodium (electrolyte) and aid in the absorption of other electrolytes and water. Non-limiting examples of suitable salts include sodium chloride, potassium chloride, ammonium chloride, powdered salt, sodium acetate, sodium citrate, and the like. In some embodiments, the salt is sodium chloride, ammonium chloride, sodium citrate, or a combination thereof. In some embodiments, the salt is sodium chloride.

[0130] Representative amounts of salt, if present, are about 0.5% by weight or more, about 1.0% by weight or more, or about 1.5% by weight or more, but typically comprise about 10% by weight or less, or about 7.5% by weight or less, or about 5% by weight or less (e.g., about 0.5 to about 5%) of the total weight of the product. In certain embodiments, the product comprises sodium chloride in an amount of about 1 to about 3% by weight, based on the total weight of the product.

[0131] Taste modifiers To improve the organoleptic properties of the products disclosed herein, the products may include one or more taste modifiers ("taste modifiers") that can act, for example, to mask, modify, block or improve the flavor of the products 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.

[0132] 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 product 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 user's oral cavity, for example, to mask the bitter taste of another component (e.g., an active ingredient). Suitable taste modifiers include, but are not limited to, capsaicin, gamma-aminobutyric acid (GABA), adenosine monophosphate (AMP), lactisol, sodium citrate, or combinations thereof.

[0133] 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 product (e.g., from about 0.01%, about 0.05%, about 0.1% or about 0.5% by weight, up to about 1%, about 5% or about 10% by weight of the total weight of the product).

[0134] Ion pairing In some embodiments, the compositions disclosed herein include a basic amine. "Basic amine" refers to a molecule that includes at least one basic amine functional group. Examples of basic amines include, but are not limited to, alkaloids. "Basic amine functional group" refers to a group that contains a nitrogen atom that has a lone pair of electrons. The basic amine functional group is attached to or incorporated within a molecule via one or more covalent bonds to said nitrogen atom. Basic amines may be primary, secondary, or tertiary amines, meaning that the nitrogen has one, two, or three covalent bonds to a carbon atom. Due to the lone pair of electrons on the nitrogen atom, such amines are referred to as "basic", meaning that the lone pair is available for hydrogen bonding. The basicity of basic amines (i.e., the electron density on the nitrogen atom, and therefore the availability and strength of hydrogen bonding to the nitrogen atom) can be affected by the nature of the neighboring atoms, the steric bulk of the molecule, and the like.

[0135] Generally, the basic amine is present in the composition or present as an active ingredient in the composition, as described herein above. Those skilled in the art will recognize that many active ingredients as defined herein are composed of molecules that can be classified as basic amines. Thus, ion pairs of such basic amine-containing active ingredients are contemplated as described herein. In some embodiments, the basic amine is caffeine. In some embodiments, the basic amine is nicotine or a nicotine moiety, each as described herein above. Generally, the basic amine (e.g., nicotine) is released from the composition and absorbed through the oral mucosa, thereby entering the bloodstream, where it is circulated throughout the body.

[0136] In some embodiments, the compositions described herein comprise an organic acid, an alkali metal salt thereof, or a combination thereof, each as further described herein below. In some embodiments, at least a portion of the basic amine is combined with at least a portion of the organic acid or alkali metal salt thereof. Depending on a number of variables (such as the concentration, pH, nature of the organic acid), the basic amine present in the composition can exist in a number of forms, including as a paired ion, in solution (i.e., fully solvated), as a free base, as a cation, as a salt, or any combination thereof. In some embodiments, the combination between the basic amine and at least a portion of the organic acid or alkali metal salt thereof is in the form of an ion pair between the basic amine and the conjugate base of the organic acid.

[0137] Ion pairing describes the partial binding of oppositely charged ions in a relatively concentrated solution to form distinct chemical species called ion pairs. The strength of the binding (i.e., ion pairing) depends on the electrostatic force of attraction between a positive ion and a negative ion (i.e., a protonated basic amine and a conjugate base of an organic acid). By "conjugate base" is meant the base generated from the deprotonation of the corresponding acid (e.g., benzoate ion is the conjugate base of benzoic acid). On average, a certain population of these ion pairs will be present at any one time, but the formation and dissociation of ion pairs is continuous. In the compositions disclosed herein and / or upon use of the compositions in the oral cavity (e.g., upon contact with saliva), the basic amine and the conjugate base of the organic acid are at least partially present in the form of ion pairs. Without wishing to be bound by theory, it is believed that such ion pairing can minimize chemical decomposition of the basic amine and / or enhance the oral availability of the basic amine (e.g., nicotine).

[0138] Those skilled in the art will recognize that the extent of ion pairing in the disclosed compositions, both before and during use by the consumer, may vary based on, for example, pH, the nature of the organic acid present in the composition, the concentration of the basic amine (e.g., nicotine), the concentration of the organic acid or the conjugate base of the organic acid, the water content of the composition, and the like. Those skilled in the art will also recognize that ion pairing is an equilibrium process that is influenced by the aforementioned variables. Thus, quantification of the extent of ion pairing is difficult or impossible 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, for example, nicotine plus the organic acid and / or their conjugate base. In particular, octanol-water partitioning, which favors the distribution of the basic amine-organic acid ion pair into octanol, predicts good absorption of the basic amine present in the composition through the oral mucosa.

[0139] organic acid As described hereinabove, in some embodiments, the product comprises an organic acid. As used herein, the term "organic acid" refers to an organic (i.e., carbon-based) compound characterized by acid properties. Typically, organic acids are relatively weak acids (i.e., they do not completely dissociate in the presence of water), such as carboxylic acids (-CO 2 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 mixture component, as opposed to an organic acid that is simply naturally present as a constituent of another mixture component (e.g., a small amount of an organic acid that may be naturally present in a mixture component, e.g., a tobacco extract).

[0140] Suitable organic acids usually have a range of lipophilicity (i.e., have polarity that provides an appropriate balance between aqueous and organic solubility). Lipophilicity is conveniently measured in terms of logP, the partition coefficient of a molecule between a lipophilic phase and an aqueous phase, usually octanol and water, respectively. Typically, the lipophilicity of suitable organic acids, expressed as logP, ranges between about 1.4 and about 4.5 (more soluble in octanol than in water). In some embodiments, the organic acid has a logP value of about 1.5 to about 4.0, e.g., from about 1.5, about 2.0, about 2.5, or about 3.0 to about 3.5, about 4.0, about 4.5, or about 5.0. Particularly suitable organic acids have a logP value of about 1.7 to about 4, e.g., from about 2.0, about 2.5, or about 3.0 to about 3.5, or about 4.0. In certain embodiments, the organic acid has a logP value of about 2.5 to about 3.5. In some embodiments, organic acids outside this range can also be utilized for various purposes and in various amounts, as described further herein below. For example, in some embodiments, the organic acid can have a logP value greater than about 4.5, e.g., about 4.5 to about 8.0. In particular, the presence of certain solvents or solubilizers (e.g., inclusion of glycerin or propylene glycol in the composition) can extend the lipophilic range (i.e., logP values ​​greater than 4.5, e.g., about 4.5 to about 8.0).

[0141] Without wishing to be bound by theory, it is believed that moderately lipophilic organic acids (e.g., logP of about 1.4 to about 4.5) form ion pairs with basic amine-containing active ingredients (e.g., nicotine), which results in better octanol-water partitioning of the ion pair, and thus are polar to partition the active ingredient (e.g., nicotine) into octanol rather than water. Such partitioning into octanol predicts favorable oral availability of the active ingredient. In some embodiments, the organic acid has a logP value of about 1.4 to about 4.5, e.g., about 1.5, about 2, about 2.5, about 3, about 3.5, about 4, or about 4.5. In some embodiments, the organic acid has a logP value of about 2.5 to about 3.5.

[0142] 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.

[0143] As used herein, "alkyl" refers to any straight or branched chain hydrocarbon. The alkyl group may be saturated (i.e., all sp 3 As used herein, the term "unsaturated" refers to a carbon-carbon, sp , or cyclic alkyl group at one or more positions within an alkyl group. 2It refers to the presence of a double bond. Unsaturated alkyl groups may be monounsaturated or polyunsaturated. Representative straight chain alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, and n-hexyl. Branched chain alkyl groups include, but are not limited to, isopropyl, sec-butyl, isobutyl, tert-butyl, isopentyl, and 2-methylbutyl. Representative unsaturated alkyl groups include, but are not limited to, ethylene or vinyl, allyl, 1-butenyl, 2-butenyl, isobutylenyl, 1-pentenyl, 2-pentenyl, 3-methyl-1-butenyl, 2-methyl-2-butenyl, 2,3-dimethyl-2-butenyl, and the like. The alkyl groups may be unsubstituted or substituted.

[0144] "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).

[0145] 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.

[0146] "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.

[0147] "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.

[0148] 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.

[0149] 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.

[0150] 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.

[0151] 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.

[0152] 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.

[0153] 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.

[0154] 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.

[0155] Examples of suitable acids include, but are not limited to, the list of organic acids in Table 1.

[0156] [Table 1]

[0157] In some embodiments, the organic acid is a monoester of a diacid or polyacid, such as monooctyl succinate, monooctyl fumarate, etc. For example, in some embodiments, the organic acid is a monoester of a dicarboxylic acid or polycarboxylic acid. In some embodiments, the dicarboxylic acid is malonic acid, succinic acid, glutaric acid, adipic acid, fumaric acid, maleic acid, or a combination thereof. In some embodiments, the dicarboxylic acid is succinic acid, glutaric acid, fumaric acid, maleic acid, or a combination thereof. In some embodiments, the dicarboxylic acid is succinic acid, glutaric acid, or a combination thereof.

[0158] 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.

[0159] 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:

[0160] [ka]

[0161] 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:

[0162] [ka]

[0163] The selection of an organic acid may further depend on additional properties, in addition to or without consideration of the mlogP 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.

[0164] In some embodiments, the organic acid is benzoic acid, toluic acid, benzenesulfonic acid, toluenesulfonic acid, hexanoic acid, heptanoic acid, decanoic acid, or octanoic acid. In some embodiments, the organic acid is benzoic acid, octanoic acid, or decanoic acid. In some embodiments, the organic acid is octanoic acid. In some embodiments, the organic acid is benzoic acid.

[0165] In some embodiments, more than one organic acid may be present. For example, a composition may include two, three, 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, three, or more organic acids, or may include different relative amounts. Thus, it is possible to include certain organic acids (e.g., citric acid or myristic acid) that have logP values ​​outside of the desired range, such that when combined with other organic acids, they provide a desired average logP range for the combination. In some embodiments, it may be desirable to include organic acids that provide, for example, but not limited to, desirable organoleptic properties, stability, as flavor ingredients in compositions that have logP values ​​outside of the desired range for a purpose. Additionally, certain lipophilic organic acids have adverse flavor and / or aroma characteristics that preclude their presence as the only organic acid (e.g., in equimolar or greater amounts compared to nicotine). Without wishing to be bound by theory, it is believed that the combination 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 undesirable from a sensory standpoint.For example, in some embodiments, the organic acid can include about 1 to about 5 molar equivalents or more of benzoic acid relative to the basic amine-containing active ingredient (e.g., nicotine), for example, combined with about 0.2 molar equivalents of octanoic acid or its salt, and 0.2 molar equivalents of decanoic acid or its salt.

[0166] 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.

[0167] In some embodiments, the composition comprises an alkali metal salt of an organic acid. For example, at least a portion of the organic acid may be present in the composition in the form of an alkali metal salt. Suitable alkali metals include lithium, sodium and potassium. In some embodiments, the alkali metal is sodium or potassium. In some embodiments, the alkali metal is sodium. In some embodiments, the composition comprises an organic acid and a sodium salt of the organic acid.

[0168] In some embodiments, the composition comprises benzoic acid and sodium benzoate, octanoic acid and sodium octanoate, decanoic acid and sodium decanoate, or combinations thereof. In some embodiments, the composition comprises benzoic acid and sodium benzoate. In some embodiments, the composition comprises sodium benzoate. In some embodiments, the ratio of organic acid to sodium salt of organic acid is from about 0.1 to about 10, e.g., from about 0.1, about 0.25, about 0.3, about 0.5, about 0.75, or about 1, to about 2, about 5, or about 10. For example, in some embodiments, both an 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. One of skill in the art will recognize that the relative amounts are determined by the desired pH of the composition, as well as the desired ionic strength. For example, an organic acid may be added in an amount that provides the desired pH level of the composition, while an alkali metal (e.g., sodium) salt is added in an amount that provides the desired range of ion pairing. Those skilled in the art will appreciate that the amount of organic acid (i.e., protonated form) present in a composition relative to the alkali metal salt or conjugate base form present in the composition will vary depending on the pH of the composition and the pKa of the organic acid, as well as the actual relative amount initially added to the composition. The amount of organic acid or its alkali metal salt present in a composition relative to the basic amine-containing active ingredient (e.g., nicotine) may vary. In general, as the concentration of the organic acid (or its conjugate base) increases, the proportion of the basic amine-containing active ingredient (e.g., nicotine) that forms an ion pair with the organic acid increases. This usually results in a logP (log of the partition coefficient) of the organic acid. 10 The partitioning of a basic amine-containing active ingredient (e.g., nicotine) in the form of an ion pair into octanol versus water is increased as measured by . In some embodiments, the compositions include from about 0.05, about 0.1, about 1, about 1.5, about 2, or about 5, to about 10, about 15, or about 20 molar equivalents of an organic acid, an alkali metal salt thereof, or a combination thereof, relative to the basic amine-containing active ingredient (e.g., nicotine), calculated as the amine-containing active ingredient free base.

[0169] In some embodiments, the 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, relative 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 the basic amine-containing active ingredient (e.g., nicotine) that is from about 1, about 2, about 3, about 4, or about 5, to about 6, about 7, about 8, about 9, or about 10. In embodiments 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.

[0170] In certain embodiments, the inclusion of the organic acid is sufficient to provide the composition with a pH of about 3.0 to about 9.5, e.g., about 3.0 to about 9.0, or about 3.0 to about 8.5, or about 3.0 to about 8.0, or about 3.5 to about 7.5, or about 4.5 to about 7.0, or about 5.5 to about 7.0, or about 4.0 to about 5.5, or about 7.0 to about 9.5. In some embodiments, the inclusion of the organic acid is sufficient to provide the composition with a pH of about 3.0, about 3.5, about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, about 7.0, about 7.5, about 8.0, about 8.5, or about 9.0. In some embodiments, the inclusion of an organic acid is sufficient to provide a 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. In particular, at alkaline pH values ​​(e.g., about 7.5 to about 9, etc.), nicotine is present predominantly in the free base form (and therefore exhibits high partitioning into octanol), while at acidic pH values ​​(e.g., about 6.5 to about 4), nicotine is present predominantly in the protonated form (and therefore exhibits lower partitioning into octanol). In some embodiments, a buffer, such as a carbonate or bicarbonate, is added to adjust and / or maintain the desired pH value. Other suitable buffers are described further herein below.

[0171] In some embodiments, the organic acid is added to the other composition components as a free acid, in pure form (i.e., natural solid or liquid form) or as a solution, e.g., a solution in water. In some embodiments, the alkali metal salt of the organic acid is added to the other composition components in pure form or as a solution, e.g., a solution in water. In some embodiments, the organic acid and the basic amine-containing active ingredient (e.g., nicotine) are combined to form a salt, either 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-containing active ingredient (e.g., nicotine) are present in the composition as individual components, and form an ion pair upon contact with moisture (saliva in the consumer's mouth).

[0172] In some embodiments, the 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 glycerin or propylene glycol.

[0173] Buffer In certain embodiments, the product of the present disclosure can include a pH adjusting agent or buffering agent. Examples of pH adjusting agents and buffering agents that can be used include, but are not limited to, metal hydroxides (e.g., alkali metal hydroxides, such as sodium hydroxide and potassium hydroxide) and other alkali metal buffers, such as metal carbonates (e.g., potassium carbonate or sodium carbonate), or metal bicarbonates, such as sodium bicarbonate. Non-limiting examples of suitable buffers include alkali metal acetates, glycinates, phosphates, glycerophosphates, citrates, carbonates, bicarbonates, borates, or mixtures thereof.

[0174] When present, the buffering agent is typically present in an amount of less than about 5% by weight based on the weight of the product, for example, from about 0.1% to about 5% by weight, e.g., from about 0.1% to about 1% by weight or from about 0.1% to about 0.5% by weight based on the total weight of the product.

[0175] Coloring agent Coloring agent can be used in an amount sufficient to bring desired physical properties to the composition.Examples of coloring agent include various dyes and pigments, such as caramel coloring agent and titanium dioxide.The amount of coloring agent utilized in the composition can vary, but when present, is usually up to about 3% by weight, for example, about 0.1% by weight, about 0.5% by weight, or about 1% by weight, up to about 3% by weight, based on the total weight of the composition.

[0176] Wetting Agent In certain embodiments, one or more humectants can be utilized in the product. Examples of humectants include, but are not limited to, glycerin, propylene glycol, and the like. When included, humectants are usually provided in an amount sufficient to provide the product with the desired moisture characteristics. Furthermore, in some cases, humectants can provide the product with desirable flow properties for deposition into a mold.

[0177] When present, humectants typically comprise about 5% or less by weight of the product (e.g., from about 0.1 to about 5% by weight), for example, from about 0.1% to about 1% by weight or from about 1% to about 5% by weight, based on the total weight of the product.

[0178] Oral Care Additives In some embodiments, the product 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 (e.g., ingredients of a formulation commercially available as ZYTEX® from Discus Dental) can be incorporated into the product. Other examples of ingredients that may be incorporated in the product in desired effective amounts may include those incorporated in the types of oral care compositions described in Takahashi et al., Oral Microbiology and Immunology, 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 contained in 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 often at least about 5% of the total dry weight of the product. The amount of oral care additive in the product typically does not exceed about 30%, often does not exceed about 25%, and often does not exceed about 20% of the total dry weight of the product.

[0179] Tobacco Materials In some embodiments, the composition may include tobacco material. The tobacco material may vary in species, variety, and form. Typically, the tobacco material is obtained from harvested plants of Nicotiana species. Exemplary Nicotiana species include N. tabacum, N. rustica, N. alata, N. arentsii, N. excelsior, N. forgetiana, N. glauca, N. glutinosa, N. gossei, N. kawakami, N. kawakamii, N. kawakamiii ... akamii, N. knightiana, N. langsdorffi, N. otophora, N. setchelli, N. sylvestris, N. tomentosa, N. tomentosiformis, N. undulata, Nx sanderae sanderae, N. africana, N. amplexicaulis, N. benavidesii, N. bonariensis, N. debneyi, N. longiflora, N. maritina, N. megalosiphon, N. occidentalis, N. paniculata, N. plumbagii N. plumbaginifolia, N. raimondii, N. rosulata, N. simulans, N. stocktonii, N. suaveolens, N. umbratica, N. velutina, N. wigandioides, N. acaulis, N. acuminata, N. attenuata.attenuata, N. benthamiana, N. cavicola, N. clevelandii, N. cordifolia, N. corymbosa, N. fragrans, N. goodspeedii, N. linearis, N. miersii, N. nudicaulis, N. obtusifolia, N. occidentalis subsp. hesperis subsp. Hersperis, N. pauciflora, N. petunioides, N. quadrivalvis, N. repanda, N. rotundifolia, N. solanifolia and N. spegazzinii. Various other types of plants representative 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 types of tobacco, growing practices, and harvesting practices are provided in Tobacco Production, Chemistry and Technology, eds. Davis et al. (1999), which is incorporated herein by reference.

[0180] 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.

[0181] 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.

[0182] 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).

[0183] 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 optionally incorporate tobacco that is fermentable. See the types of tobacco processing techniques described in PCT WO2005 / 063060 to Atchley et al. This is incorporated herein by reference.

[0184] 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% by weight or less than about 15% by weight. 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.

[0185] 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, 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% to less than about 5% by weight. 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% by weight, often less than about 20%, and frequently less than about 15% by weight.

[0186] For the preparation of oral products, it is common to subject harvested plants of Nicotiana species to a curing process. The tobacco materials incorporated into the mixture for inclusion in the products disclosed herein are suitably 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 curing processes, such as flame curing or sun curing.

[0187] 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.

[0188] 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.

[0189] 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 processes previously described.

[0190] 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.

[0191] In some embodiments, a type of tobacco material is first selected that is visually somewhat lighter in color than the 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 and described above for bleaching active ingredients.

[0192] Typical inclusion ranges for tobacco material may vary depending on the nature and type of tobacco material and its intended effect on the final composition, with exemplary ranges being up to about 30% by weight (or up to about 20% by weight, or up to about 10% by weight, or up to about 5% by weight) based on the total weight of the composition (e.g., about 0.1 to about 15% by weight). In some embodiments, products of the present disclosure may be characterized as being completely free or substantially free of tobacco material (other than purified nicotine as the active ingredient). For example, certain embodiments may be characterized as having less than 1% by weight, 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.

[0193] Processing Aids Processing aids (e.g., flow aids) can also be included in product ingredients if necessary for downstream processing of the product ingredients, such as granulation or blending, or the product itself, such as tabletting, for example to enhance the flow or compaction of the ingredients. Exemplary processing aids include microcrystalline cellulose, silica, polyethylene glycol, stearic acid, calcium stearate, magnesium stearate, zinc stearate, sodium stearyl fumarate, carnauba wax, and combinations thereof. In some embodiments, the processing aid is a flow aid. In some embodiments, the flow aid is silica, stearic acid, magnesium stearate, or combinations thereof.

[0194] A representative amount of processing aid, when present, may comprise at least about 0.5 percent or at least about 1 percent of the total weight of the composition. Preferably, the amount of processing aid in the composition does not exceed about 5 percent, and often does not exceed about 3 percent, of the total weight of the composition.

[0195] Other Additives Other additives may be included in the disclosed products. For example, product ingredients may be processed, blended, compounded, combined, and / or mixed with other materials or ingredients to form a final product. Additives may be artificial or may be obtained or derived from herbal or biological sources. Examples of additional types of additives may include thickening or gelling agents (e.g., fish gelatin), emulsifiers, preservatives (e.g., potassium sorbate, etc.), disintegration aids, or combinations thereof. See, for example, representative components, combinations of components, relative amounts of the components, and modes and methods for utilizing the components, as described in U.S. Pat. No. 9,237,769 to Mua et al., U.S. Pat. No. 7,861,728 to Holton, Jr. et al., U.S. Pat. App. Pub. No. 2010 / 0291245 to Gao et al., and U.S. Pat. App. Pub. No. 2007 / 0062549 to Holton, Jr. et al., each of which is incorporated herein by reference.

[0196] Typical inclusion ranges for such additional additives may vary depending on the nature and function of the additive and its intended effect on the final product, 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 product.

[0197] In some embodiments, the composition includes a magnesium salt. A non-limiting example of a suitable magnesium salt is magnesium gluconate. In some embodiments, the composition includes magnesium in an amount of about 0.1% to about 2% or about 0.2 to about 1% by weight based on elemental magnesium.

[0198] The above-mentioned additives may be utilized together (e.g., as an additive blend) or separately (e.g., individual additive components may be added at different stages involved in the preparation of the final mixture). Furthermore, the above-mentioned types of additives may be encapsulated when provided in the final product. Examples of encapsulated additives are described, for example, in International Application Publication No. WO2010 / 132444 to Atchley, which has been previously incorporated by reference herein.

[0199] particle In some embodiments, both the product ingredients and the overall product described herein may be described as a granular material. As used herein, the term "granular" refers to a material in the form of a plurality of individual particles, some of which may be in the form of an agglomeration of a plurality of particles, the particles having an average length to width ratio of less than 2:1, such as less than 1.5:1, such as less than about 1:1. In various embodiments, the particles of the granular material may be described as substantially spherical or granular.

[0200] The particle size of a granular material may be measured by sieve analysis. As one skilled in the art will readily appreciate, sieve analysis (otherwise known as gradient testing) is a method used to measure the particle size distribution of a granular material. Typically, sieve analysis involves a column of nested sieves, the sieves preferably comprising screens in the form of wire mesh fabric. A pre-weighed sample may be introduced into the upper or top sieve in the column, which has the largest screen opening or mesh size (i.e. the largest pore diameter of the sieve). Each sieve lower in the column has a progressively smaller screen opening or mesh size than the sieve at the top. Typically, the bottom of the sieve column has a receiver section that collects any particles having a particle size smaller than the screen opening or mesh size of the bottom or bottommost sieve in the column (which has the smallest screen opening or mesh size).

[0201] In some embodiments, the column of sieves may be placed on or in a mechanical agitator. The agitator causes vibration of each of the sieves in the column. The mechanical agitator may be run for a predetermined period of time to ensure that all particles are collected on the correct sieve. In some embodiments, the column of sieves is agitated for a period of 0.5 minutes to 10 minutes, such as 1 minute to 10 minutes, such as 1 minute to 5 minutes, such as approximately 3 minutes. Once the agitation of the sieves in the column is complete, the material collected on each sieve is weighed. The weight of each sample on each sieve is then divided by the total weight to obtain the percentage of mass retained on each sieve. Those skilled in the art will readily recognize that the screen opening size or mesh size for each sieve in the column used for sieve analysis may be selected based on the particle size of the sample to be analyzed or the known maximum / minimum particle size. In some embodiments, a column of sieves may be used for sieve analysis, the column comprising 2 to 20 sieves, for example 5 to 15 sieves. In some embodiments, a column of sieves may be used for sieve analysis, the column comprising 10 sieves. In some embodiments, the largest screen opening or mesh size of the sieve used for sieve analysis may be 1000 μm, for example 500 μm, for example 400 μm, for example 300 μm.

[0202] In some embodiments, any particulate material referred to herein (e.g., fillers, non-tobacco botanical materials, and all products) may be characterized in that at least 50% by weight of the particles have a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis. In some embodiments, at least 60% by weight of the particles of any particulate material referred to herein have a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis. In some embodiments, at least 70% by weight of the particles of any granular material referred to herein have a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis. In some embodiments, at least 80% by weight of the particles of any granular material referred to herein have a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis. In some embodiments, at least 90% by weight of the particles of any granular material referred to herein have a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis. In some embodiments, at least 95% by weight of the particles of any particulate material referred to herein have a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis. In some embodiments, at least 99% by weight of the particles of any particulate material referred to herein have a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, such as about 300 μm or less, as measured by sieve analysis.In some embodiments, substantially 100% by weight of the particles of any particulate material referred to herein have a particle size of about 1000 μm or less, such as about 500 μm or less, such as about 400 μm or less, such as about 350 μm or less, for example about 300 μm or less, as measured by sieve analysis.

[0203] In some embodiments, at least 50% by weight, such as at least 60% by weight, for example at least 70% by weight, such as at least 80% by weight, for example at least 90% by weight, for example at least 95% by weight, for example at least 99% by weight, of the particles of any particulate material referred to herein have a particle size of from about 0.01 μm to about 1000 μm, such as from about 0.05 μm to about 750 μm, for example from about 0.1 μm to about 500 μm, for example from about 0.25 μm to about 500 μm, as measured by sieve analysis. In some embodiments, at least 50% by weight, such as at least 60% by weight, for example at least 70% by weight, such as at least 80% by weight, for example at least 90% by weight, for example at least 95% by weight, for example at least 99% by weight, of the particles of any particulate material referred to herein have a particle size of from about 10 μm to about 400 μm, such as from about 50 μm to about 350 μm, for example from about 100 μm to about 350 μm, for example from about 200 μm to about 300 μm, as measured by sieve analysis.

[0204] Built for oral use A product that is structured for oral use is provided herein. The term "structured for oral use" as used herein means that the product is provided in such a form that one or more components of the product (e.g., flavoring agent and / or active ingredient) are carried into the mouth of the user by the saliva in the user's mouth during use. In certain embodiments, the product is adapted to deliver a component to the user via the user's oral mucosa, the user's digestive system, or both, and in some cases, the component is an active ingredient (e.g., including but not limited to, an irritant) that can be absorbed via the oral mucosa or absorbed via the digestive tract when the product is used.

[0205] In some embodiments, the product is in granular form. "Granular form" means that the product consists of relatively large uniform multiparticulate entities. Such granules containing the individual components of the product are generally prepared by granulation of the individual components in powder form, as further described herein below.

[0206] In some embodiments, the granules are compressed into a predetermined shape. The product can be formed into a variety of shapes, including pills, tablets, spheres, cubes, beads, ovals, or obloids. The cross-sectional shape of the product can vary, and example cross-sectional shapes include round, square, rectangular, oblong, etc. Such shapes can be formed in a variety of ways using equipment, such as moving belts, nips, extruders, granulators, compression equipment, etc.

[0207] In certain embodiments, the product is in the form of compressed or molded pellets, which can have any of a variety of shapes, including traditional pill or tablet shapes. The exact shape and size of such pellets is not critical. Certain embodiments of the present disclosure are described with reference to Figures 1 and 2, which provide non-limiting examples of possible product shapes. With reference to Figure 1, a perspective view shows an embodiment of the product in the form of a tablet having a diameter and a thickness. With reference to Figure 2, a perspective view shows an embodiment of the product in the form of a tablet having an oval shape, with a length, a width, and a thickness. The dimensions vary based on the weight of the pellet. Exemplary pellet sizes include pellets having lengths and widths ranging from about 3 mm to about 20 mm, and more typically from about 5 to about 18 mm. Exemplary pellet sizes include pellets having thicknesses ranging from about 3 to about 10 mm.

[0208] Exemplary pellet weights range from about 250 mg to about 1500 mg, for example, from about 250 mg to about 700 mg, or from about 700 mg to about 1500 mg, or from about 300 mg to about 450 mg.

[0209] In some embodiments, the product in the form of a compressed or molded pellet, including an optional outer coating comprising shellac, carnauba wax, paraffin wax, beeswax, palm oil, sunflower oil, or combinations thereof.

[0210] Product preparation The products of the present disclosure may generally be prepared, for example, by dry blending dry ingredients such as fillers, active ingredients, sugar alcohols, non-tobacco botanical materials, etc., and combining the dry mixture with liquid ingredients such as water, binders, etc. The manner in which the various components of the product (e.g., fillers, active ingredients, sugar alcohols, non-tobacco botanical materials, etc.) are combined may vary. Thus, the overall product may be of relatively uniform nature (e.g., homogeneous). The above-mentioned ingredients may be in liquid or dry solid form and may be admixed in a pre-processing step prior to mixing with any remaining ingredients of the product, or may simply be mixed together with all other liquid or dry ingredients.

[0211] The various components of the product can be contacted, combined, or mixed together using any mixing technique or device known in the art. Any mixing method that brings the product 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 type blenders, ribbon blenders, mixers available from Littleford Day, Inc., such as FKM130, FKM600, FKM1200, FKM2000, and FKM3000, Plough Share type mixer cylinders, Hobart mixers, and the like. Also see, for example, the types of methodologies described in U.S. Patent No. 4,148,325 to Solomon et al.; U.S. Patent No. 6,510,855 to Korte et al.; and U.S. Patent No. 6,834,654 to Williams, each of which is incorporated herein by reference. In some embodiments, the components that form the product are prepared so that the mixture can be used in starch molding process to form the product.The manner and method of compounding the product are clear to those skilled in the art.See, for example, the types of methods described in U.S. Patent No. 4,148,325 to Solomon et al.; U.S. Patent No. 6,510,855 to Korte et al.; and U.S. Patent No. 6,834,654 to Williams, U.S. Patent No. 4,725,440 to Ridgway et al. and U.S. Patent No. 6,077,524 to Bolder et al., each of which is incorporated herein by reference.

[0212] In some embodiments, the product of the present disclosure is prepared by a method comprising combining at least one filler with at least one sugar alcohol to form a mixture, and blending the mixture. In some embodiments, the blended mixture comprises at least one active ingredient, at least one flavoring agent, or a combination thereof. In some embodiments, the blended mixture comprises a non-tobacco botanical material. In some embodiments, the blended mixture comprises a sweetener. The blended mixture is usually relatively dry, meaning that no liquid ingredients are introduced, and instead, the mixture contains substantially all dry powder ingredients, and is referred to as a "dry blend".

[0213] In some embodiments, the dry blend is then granulated to form a plurality of granules. Granulation is a process in which particles of individual components, for example in powder form, are made to adhere to form large, uniform, and multiple particulate entities called granules. Granulation is particularly suitable in embodiments in which the product includes milled non-tobacco botanical materials, botanical extracts, or certain flavorings. Milled botanical materials and extracts, as well as certain flavorings, due to their high moisture and / or oil content, tend to adhere together and form agglomerates that may result in a non-uniform product in the absence of granulation. Such agglomeration is also undesirable during processing, as it may lead to difficulties in achieving proper flowability and is particularly undesirable in compressed (e.g., tableted) embodiments. Thus, the granulation method disclosed herein is particularly advantageous in such embodiments, where such materials are incorporated into a dry blend and then the dry blend is granulated, advantageously reducing or avoiding adhesion and / or compression defects. Any suitable means for granulation may be utilized, for example, granulation may be carried out in a granulator under high shear, low shear, fluidized bed, rotor or melt granulation.

[0214] The dry blend can be mixed with a liquid binder or an aqueous binder solution (e.g., by spraying the aqueous binder solution into a granulator) and granulated to a desired particle size, e.g., about 100 to about 200 microns. The dry blend is typically granulated with an aqueous binder solution to form a plurality of granules. As understood in the art, the aqueous binder solution promotes the agglomeration of the dry powder granulation mixture into larger granules. The aqueous binder solution used in the granulation process can be either an aqueous or alcohol-based solution containing a suitable binder or combination of binders. In some embodiments, the binder comprises a cellulose ether as described hereinabove. In some embodiments, the binder comprises polyvinylpyrrolidone or a combination of cellulose ether and polyvinylpyrrolidone. In some embodiments, the binder is polyvinylpyrrolidone. The molecular weight of the polyvinylpyrrolidone can vary and is generally designated by reference to the letter "K" followed by a number. For example, in some embodiments, the polyvinylpyrrolidone is K29 / 32 or K30, meaning that the polyvinylpyrrolidone has an average molecular weight of 29,000 to 32,000 or 30,000, respectively.

[0215] The aqueous binder solution typically has a solids content of about 3 to about 20 percent (w / w), and suitable solvents include water and ethanol. The aqueous binder solution used in the granulation process can be aqueous in nature. In some embodiments, the aqueous binder solution includes at least one active ingredient, at least one flavoring agent, or a combination thereof. The aqueous binder solution, the dry blend, or both, can contain other additives, including any of the additives discussed herein, such as salts, buffers, non-tobacco botanical materials, sweeteners, processing aids, and the like. Such additives may be added before or after granulation.

[0216] In certain embodiments, it may be advantageous to introduce at least flavoring agent at a later stage of processing, for example, during or after granulation.Specifically, certain flavoring agents are volatile or undergo decomposition, and their presence may decrease in the product if they are introduced early, for example, in a dry blend.Therefore, in certain embodiments, the dry blend does not contain flavoring agent, and at least one flavoring agent is introduced during granulation, after granulation (for example, as a coating on the surface of the granulated material or by spraying), or both.In such embodiments, the evaporation and loss of flavoring agent can be avoided or reduced.

[0217] In some embodiments, after granulation, the granules are typically dried to a moisture level of less than about 7.0 weight percent, more typically less than about 6.5 weight percent, and often less than about 6.0 weight percent (e.g., in the range of about 4.0 to about 7.0 weight percent). An exemplary moisture level is about 5.5 weight percent.

[0218] In other embodiments, pellets containing product ingredients may be formed using rotor granulation, where a layer of dry powder, for example, including at least one filler and at least one sugar alcohol, is stacked on a substantially spherical core material surface to form a roughly spherical pellet product. The core material can vary, but typically includes a compressible powder material, such as microcrystalline cellulose, sugar or salt. The core material can also incorporate non-tobacco botanical materials, if desired. The diameter of the core material is typically between about 600 microns and about 3,000 microns. Large core sizes can be advantageous, since layering efficiency increases with increasing core size. Commercially available microcrystalline cellulose, having a size range of about 700 to about 900 microns, is an exemplary core material.

[0219] In such an embodiment, the core material is fed into a rotor granulator, such as a GXR-35 GRANUREX® rotor processor available from Vector Corporation, and the desired powder coating material and accompanying aqueous binder solution are applied to the core material to build an additional layer on the core surface and improve the size of the spherical pellets. The powder coating material typically contains fillers as the main ingredient along with other dry powder components including any of the additives specified herein, such as salts, active ingredients, flavoring agents, sweetening agents, binders, buffering agents, coloring agents, humectants, oral care additives, preservatives, syrups, disintegration aids, antioxidants, herbal or botanical materials, flow aids, compression aids, and combinations thereof. The particle size of the powder material used in the rotor granulation process can vary, but the efficiency of the layering process improves with increasing particle size.

[0220] Exemplary aqueous binder solutions for rotor granulation processes include aqueous or alcohol-based solutions of polymeric binders, including povidone, hydroxypropylcellulose, or combinations thereof, and may contain other additives, including any of the additives discussed herein, such as mannitol, maltodextrin, sweeteners, flavorings, and the like. Aqueous binder solutions typically have a solids content of about 3 to about 20 percent (w / w), and suitable solvents include water and ethanol. Ethanol or other alcohol solvents are advantageous in some embodiments, since the use of non-aqueous solvents can reduce the moisture level in the pellets. This can reduce the drying time required to prepare the final product.

[0221] In some embodiments, the method further comprises contacting the granulated material with at least one flavoring agent, such as by spray application.

[0222] In some embodiments, the product is in the form of a compressed pellet or tablet. Thus, in some embodiments, the method further comprises forming the plurality of granules into a preformed shape. The plurality of granules may be compressed using conventional tableting techniques. The compressed product pellet or tablet may be produced by compressing the plurality of granules, including any relevant formulation components, in the form of pellets or tablets. Exemplary compression equipment, such as compression presses, are available as Colton 2216 and Colton 2247 from Vector Corporation, and 1200i, 2200i, 3200, 2090, 3090, and 4090 from Fette Compacting. Equipment for applying an outer coating layer to the compressed pelletized product is available as CompuLab 24, CompuLab 36, Accela-Cota 48, and Accela-Cota 60 from Thomas Engineering.

[0223] The product in the form of compressed pellets or tablets can include an optional outer coating, which can help improve the storage stability of the product and improve the packaging process by reducing friability and dusting. The coating typically includes a film-forming polymer, such as a cellulosic material, an optional plasticizer, and optional flavorings, colorants, salts, sweeteners, or other additives of the type described herein. Thus, in some embodiments, the method further includes coating the preformed shape with a coating composition. The coating composition is typically aqueous in nature and can be applied using any pellet or tablet coating technique known in the art, such as pan coating. Exemplary film-forming polymers include cellulosic materials, such as methylcellulose, hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose, and carboxymethylcellulose (CMC). Exemplary plasticizers include aqueous solutions or emulsions of glyceryl monostearate and triethyl citrate. Additional potential coating agents include food grade shellac, waxes such as carnuaba wax, paraffin wax and beeswax, oils such as palm oil and sunflower oil, and combinations thereof.

[0224] In one embodiment, the coating composition comprises up to about 75 weight percent of a film-forming polymer solution (e.g., about 40 to about 70 weight percent, based on the total weight of the coating formulation), up to about 5 weight percent of a plasticizer (e.g., about 0.5 to about 2 weight percent), up to about 5 weight percent of a sweetener (e.g., about 0.5 to about 2 weight percent), up to about 10 weight percent of one or more colorants (e.g., about 1 to about 5 weight percent), up to about 5 weight percent of one or more flavoring agents (e.g., about 0.5 to about 3 weight percent), up to about 2 weight percent of a salt, e.g., NaCl (e.g., about 0.1 to about 1 weight percent), and the balance water. In some embodiments, the coating comprises at least one flavoring agent.

[0225] After optional coating, the product can be dried to a final desired moisture level. The moisture content of the product can vary before use by the user. Typically, the moisture content of the product is in the range of about 2 to about 6 weight percent (e.g., about 4 percent) based on the total weight of the product unit as present in a single unit of the product before being inserted into the mouth of the user. Control of the final moisture of the product can be important for storage stability.

[0226] The manner in which the moisture content of the product is controlled may vary. For example, the product may be subjected to heat or convection heating. As a specific example, the product may be oven dried in heated air at a temperature of about 40°C to about 95°C, with a preferred temperature range of about 60°C to about 80°C, for a suitable length of time to obtain the desired moisture content.

[0227] The hardness of the products of the present disclosure can vary, but is typically at least about 5 kp (kiloponds), more often at least about 8 kp, and most often at least about 10 kp or at least about 12 kp (e.g., a hardness range of about 5 kp to about 20 kp or about 8 kp to about 15 kp). Hardness can be measured using a hardness tester, such as a Varian VK200 or equivalent.

[0228] The product may be packaged in any suitable inner packaging material and / or outer container, see, for example, U.S. Patent No. 7,014,039 to Henson et al.; U.S. Patent No. 7,537,110 to Kutsch et al.; U.S. Patent No. 7,584,843 to Kutsch et al.; U.S. Patent No. D592,956 to Thiellier and U.S. Patent No. D594,154 to Patel et al.; U.S. Patent Publication No. 2008 / 0173317 to Robinson et al.; U.S. Patent No. 2009 / 0014343 to Clark et al.; U.S. Patent No. 2009 / 0014450 to Bjorkholm; U.S. Patent No. 2009 / 0250360 to Bellamah et al.; U.S. Patent No. 2009 / 0266837 to Gelardi et al.; U.S. Patent No. 2009 / 0223989 to Gelardi. See also U.S. Patent Application Nos. 2009 / 0230003 to Thiellier, 2010 / 0084424 to Gelardi, and 2010 / 0133140 to Bailey et al., as well as the various types of containers for smokeless type products described in U.S. Patent Application Nos. 29 / 342,212, filed August 20, 2009 to Bailey et al., 12 / 425,180, filed April 16, 2009 to Bailey et al., 12 / 685,819, filed January 12, 2010 to Bailey et al., and 12 / 814,015, filed June 11, 2010 to Gelardi et al., all of which are incorporated herein by reference.

[0229] Many variations and other embodiments of the invention to which this invention pertains will be devised by one skilled in the art having the benefit of the teachings presented in the foregoing description. It is to be understood, therefore, that the invention is not limited to the specific embodiments disclosed, and that variations and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation. EXAMPLES

[0230] Aspects of the present invention are further illustrated by the following examples, which are provided to illustrate certain specific aspects of the invention and should not be construed as limiting the invention.

[0231] Example 1. Wet granulation In one embodiment, a granulation is prepared containing the ingredients set forth below in Table 1. The actual ingredients and percentages may vary depending on the desired characteristics of the final product.

[0232] The dry materials (botanical materials, sweeteners, fillers, sugar alcohol) are each passed through an 18 mesh screen and then mixed in a V-blender until uniform. The resulting dry blend is contacted with an aqueous solution of salt and vinylpyrrolidone in a granulator. Granulation is continued until the desired granule size is obtained, which is generally in the range of about 60 μm to about 600 μm, or about 200 μm to about 500 μm.

[0233] [Table 2]

[0234] Example 2. Tableting In one embodiment, tablets are prepared from the granules of Example 1.

[0235] Optionally, additional flavorings are added to the granules. Die-cut lubricants (e.g., stearic acid, magnesium stearate, silica, sodium stearyl fumarate or combinations thereof) are added as necessary for processing, and then mixed. Tablets are prepared from the mix using a die-cut press to form tablets weighing about 800 mg or about 1000 mg, respectively. The compression force used depends on the composition, weight and shape, and can be determined by those skilled in the art.

[0236] Example 3. Coating agent The tablets of Example 2 are coated in a pan coater with an aqueous coating solution consisting essentially of a 10% hydroxypropyl methylcellulose solution containing trace amounts of titanium dioxide, sweeteners, flavors, colors, and PlasACRYL® coating plasticizer.

Claims

1. A method for preparing a product constructed for oral use, comprising: blending at least one filler, at least one sugar alcohol, and an active ingredient, a flavoring agent, or both to form a dry blend; and granulating a combination of the dry blend and an aqueous binder solution to form a plurality of granules .

2. The method according to claim 1, wherein the dry blend comprises an active ingredient and a flavoring agent.

3. The method according to claim 1, wherein the dry blend comprises an active ingredient and substantially no flavoring agent.

4. The method according to claim 1, wherein the granules have a size in the range of about 60 μm to about 500 μm.

5. The method according to claim 1, further comprising compressing the plurality of granules into a predetermined shape.

6. The method according to claim 5, wherein the predetermined shape is a pellet or a tablet.

7. The method according to claim 5, further comprising mixing the plurality of granules with at least one flavoring agent or glidant, or both, prior to the compressing step.

8. The method according to claim 5, further comprising mixing the plurality of granules with at least one flavoring agent and a glidant prior to the compressing step.

9. The method according to claim 8, wherein the glidant is selected from the group consisting of microcrystalline cellulose, silica, polyethylene glycol, stearic acid, calcium stearate, magnesium stearate, zinc stearate, sodium stearyl fumarate, carnauba wax, and combinations thereof.

10. The method according to claim 1, further comprising applying a coating composition to the product.

11. The method according to claim 10, wherein the coating composition comprises a cellulosic material.

12. The method according to claim 10, wherein the coating composition comprises a flavoring agent.

13. The method according to claim 1, wherein the at least one filler comprises calcium carbonate, microcrystalline cellulose, maltodextrin, corn starch, or combinations thereof.

14. The method according to claim 1, wherein the aqueous binder solution comprises a binder selected from the group consisting of methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, polyvinylpyrrolidone, and combinations thereof.

15. The method according to claim 1, wherein the binder aqueous solution contains polyvinylpyrrolidone.

16. The method according to claim 1, wherein at least one sugar alcohol is selected from the group consisting of erythritol, isomalt, maltitol, mannitol, sorbitol, and combinations thereof.

17. The method according to claim 1, wherein at least one sugar alcohol is mannitol.

18. The method according to claim 1, wherein the active ingredient is selected from the group consisting of nicotine components, botanical materials, dietary supplements, stimulants, amino acids, vitamins, cannabinoids, cannabimetics, terpenes, and combinations thereof.

19. The method according to claim 1, wherein the active ingredient is a non-tobacco botanical material.

20. The method according to claim 19, wherein the non-tobacco botanical material is in a milled form or in the form of an extract.

21. The method according to claim 1, wherein the product constructed for oral use contains from about 0.001 to about 10% by weight of a nicotine component, calculated as the free base, based on the total dry weight of the composition.

22. The method according to claim 1, wherein the product constructed for oral use is substantially free of tobacco materials, excluding any nicotine components present.

23. The method according to claim 1, further comprising adding one or more of salts, sweeteners, buffering agents, colorants, wetting agents, oral care additives, preservatives, disintegrating aids, flow aids, compression aids, or combinations thereof to the dry blend, the binder aqueous solution, or both.

24. A product constructed for oral use, comprising a plurality of granules, wherein the granules contain at least one filler; a liquid binder, at least one sugar alcohol; and an active ingredient, a flavoring agent, or both.

25. At least one filler contains a filler selected from the group consisting of calcium carbonate, microcrystalline cellulose, maltodextrin, corn starch, and combinations thereof, the liquid binder contains polyvinylpyrrolidone, at least one sugar alcohol contains mannitol, at least one active ingredient is a milled non-tobacco botanical material, The product according to claim 24.

26. The product according to claim 25, wherein the product is in the form of a compressed pellet or tablet having an outer surface, and further comprises a coating on the outer surface, the coating containing a flavoring agent.

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