Nanoemulsion for oral use

Abstract

The present disclosure provides nanoemulsions comprising oil, water, an emulsifier, and an active ingredient, a flavoring material, or a combination thereof. The nanoemulsions are intended for oral human use.

Description

Technical Field

[0001] The present disclosure relates to products for human use. The products are configured for oral use and deliver substances such as flavors and / or active ingredients during use. Such products may include tobacco or products derived from tobacco, or may be tobacco-free alternatives.

Background Art

[0002] Tobacco can be enjoyed in so-called "smokeless" forms. Particularly popular smokeless tobacco products are used by inserting some form of processed tobacco or tobacco-containing formulation into the user's mouth. Such smokeless tobacco products typically include moist snuff, snus, and chewing tobacco, and generally consist of mostly granular, pelleted or cut tobacco, either divided by the user or presented to the user in individual portions such as single-use pouches or sachets. Other traditional forms of smokeless products include compressed or agglomerated forms such as plugs, tablets or pellets. Alternative product forms such as tobacco-containing gums and mixtures of tobacco with other plant materials are also known.For example, see the types of smokeless tobacco formulations, ingredients, and processing methods described in U.S. Patent Nos. 1,376,586 (Schwartz); 4,513,756 (Pittman et al.); 4,528,993 (Sensabaugh, Jr. et al.); 4,624,269 (Story et al.); 4,991,599 (Tibbetts); 4,987,907 (Townsend); 5,092,352 (Sprinkle, III et al.); 5,387,416 (White et al.); 6,668,839 (Williams); 6,834,654 (Williams); 6,953,040 (Atchley et al.); 7,032,601 (Atchley et al.) and 7,694,686 (Atchley et al.); U.S. Patent Publications 2004 / 0020503 (Williams); 2005 / 0115580 (Quinter et al.); 2006 / 0191548 (Strickland et al.); 2007 / 0062549 (Holton, Jr. et al.); 2007 / 0186941 (Holton, Jr. et al.); 2007 / 0186942 (Strickland et al.); 2008 / 0029110 (Dube et al.); 2008 / 0029116 (Robinson et al.); 2008 / 0173317 (Robinson et al.); 2008 / 0209586 (Neilsen et al.); 2009 / 0065013 (Essen et al.) and 2010 / 0282267 (Atchley), and WO2004 / 095959 (Arnarp et al.), each of which is incorporated herein by reference.

[0003] Configurations of smokeless tobacco products that combine tobacco materials with various binders and fillers have been proposed more recently, and as product forms by way of example, lozenges, troches, gels, extruded forms, etc. are mentioned. For example, see the product types described in U.S. Patent Application Publication Nos. 2008 / 0196730 (Engstrom et al.); 2008 / 0305216 (Crawford et al.); 2009 / 0293889 (Kumar et al.); 2010 / 0291245 (Gao et al.); 2011 / 0139164 (Mua et al.); 2012 / 0037175 (Cantrell et al.); 2012 / 0055494 (Hunt et al.); 2012 / 0138073 (Cantrell et al.); 2012 / 0138074 (Cantrell et al.); 2013 / 0074855 (Holton, Jr.); 2013 / 0074856 (Holton, Jr.); 2013 / 0152953 (Mua et al.); 2013 / 0274296 (Jackson et al.); 2015 / 0068545 (Moldoveanu et al.); 2015 / 0101627 (Marshall et al.), and 2015 / 0230515 (Lampe et al.), each of which is incorporated herein by reference.

[0004] All-white snus portions are increasing in popularity and provide separate aesthetically pleasing alternatives to traditional snus. Such modern "white" pouch products may contain decolorized tobacco or may be tobacco-free.

Prior Art Documents

Patent Documents

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[0006] [Brief Summary] The present disclosure generally provides nanoemulsions comprising oil, water, an emulsifier, and an active ingredient, a flavoring agent, or a combination thereof. Further provided are products and compositions configured for oral use each comprising a nanoemulsion disclosed herein. Thus, in one aspect, the present disclosure provides a nanoemulsion comprising oil, water, an emulsifier, and an active ingredient, a flavoring agent, or a combination thereof.

[0007] In some embodiments, the oil comprises a long-chain fatty acid, a monoacylglycerol, a diacylglycerol, a triacylglycerol, or a combination thereof, and the acyl group is a long-chain fatty acid. In some embodiments, the oil comprises mineral oil, castor oil, corn oil, coconut oil, meadowfoam oil, linseed oil, olive oil, peanut oil, soybean oil, safflower oil, flaxseed oil, sunflower oil, olive oil, or a combination thereof.

[0008] In some embodiments, the active ingredient is lipophilic. In some embodiments, the active ingredient is a generally oxidizable molecule. In some embodiments, the active ingredient is selected from the group consisting of plant materials, stimulants, amino acids, vitamins, antioxidants, nicotine components, cannabinoids, drugs, and combinations thereof.

[0009] In some embodiments, the flavoring agent is lipophilic. In some embodiments, the flavoring agent is a generally oxidizable molecule. In some embodiments, the flavoring agent comprises citrus oil.

[0010] In some embodiments, the emulsifier is a surfactant, a phospholipid, an amphiphilic polysaccharide, an amphiphilic protein, or a combination thereof. In some embodiments, the emulsifier is an ionic surfactant or a non-ionic surfactant. In some embodiments, the emulsifier comprises Tween20, Tween80, Span20, Span40, Span60, Span80, lecithin, hydrocolloid gum, modified starch, or a combination thereof. In some embodiments, the emulsifier is present in an amount of up to about 15 wt%.

[0011] In some embodiments, the nanoemulsion further comprises a stabilizer selected from the group consisting of polysaccharides and polyols.

[0012] In some embodiments, the nanoemulsion comprises nanoparticles having a size of about 20 to about 200 nm. In some embodiments, the zeta potential of the nanoparticles is from about -40 mV to about 40 mV. In some embodiments, the nanoemulsion comprises particles having a polydispersity index of less than about 0.3.

[0013] In another aspect, provided is a pouch product configured for oral use, comprising the nanoemulsion according to claim 1 enclosed in a pouch. In some embodiments, the pouch product further comprises a filler, and the nanoemulsion is dispersed or disposed in the filler. In some embodiments, the pouch product is substantially free of nicotine.

[0014] The present disclosure includes, but is not limited to, the following embodiments.

[0015] Embodiment 1: A nanoemulsion comprising oil, water, an emulsifier, and an active ingredient, a flavoring material, or a combination thereof.

[0016] Embodiment 2: The nanoemulsion according to Embodiment 1, wherein the oil comprises a long-chain fatty acid, a monoacylglycerol, a diacylglycerol, a triacylglycerol, or a combination thereof, and the acyl group is a long-chain fatty acid.

[0017] Embodiment 3: The oil includes mineral oil, castor oil, corn oil, coconut oil, perilla oil, linseed oil, olive oil, peanut oil, soybean oil, safflower oil, flaxseed oil, sunflower oil, olive oil, or a combination thereof, and is the nanoemulsion according to any one of Embodiments 1 or 2.

[0018] Embodiment 4: The nanoemulsion according to any one of Embodiments 1 to 3, wherein the active ingredient is lipophilic.

[0019] Embodiment 5: The nanoemulsion according to any one of Embodiments 1 to 4, wherein the active ingredient is a generally oxidizable molecule.

[0020] Embodiment 6: The nanoemulsion according to any one of Embodiments 1 to 5, wherein the active ingredient is selected from the group consisting of plant materials, stimulants, amino acids, vitamins, antioxidants, nicotine components, cannabinoids, cannabis analogs, terpenes, drugs, and combinations thereof.

[0021] Embodiment 7: The nanoemulsion according to any one of Embodiments 1 to 6, wherein the flavoring material is lipophilic.

[0022] Embodiment 8: The nanoemulsion according to any one of Embodiments 1 to 7, wherein the flavoring material is a generally oxidizable molecule.

[0023] Embodiment 9: The nanoemulsion according to any one of Embodiments 1 to 8, wherein the flavoring material includes citrus oil.

[0024] Embodiment 10: The nanoemulsion according to any one of Embodiments 1 to 9, wherein the emulsifier is a surfactant, a phospholipid, an amphiphilic polysaccharide, an amphiphilic protein, or a combination thereof.

[0025] Embodiment 11: The nanoemulsion according to any one of Embodiments 1 to 10, wherein the emulsifier is an ionic surfactant or a non-ionic surfactant.

[0026] Embodiment 12: The nanoemulsion according to any one of Embodiments 1 to 11, wherein the emulsifier comprises Tween 20, Tween 80, Span 20, Span 40, Span 60, Span 80, lecithin, hydrocolloid gum, modified starch, or a combination thereof.

[0027] Embodiment 13: The nanoemulsion according to any one of Embodiments 1 to 12, wherein the emulsifier is present in an amount of up to about 15% by weight.

[0028] Embodiment 14: The nanoemulsion according to any one of Embodiments 1 to 13, further comprising a stabilizer selected from the group consisting of polysaccharides and polyols.

[0029] Embodiment 15: The nanoemulsion according to any one of Embodiments 1 to 14, comprising nanoparticles having a size of about 20 to about 200 nm.

[0030] Embodiment 16: The nanoemulsion according to any one of Embodiments 1 to 15, wherein the zeta potential of the nanoparticles is from about -40 mV to about 40 mV.

[0031] Embodiment 17: The nanoemulsion according to any one of Embodiments 1 to 16, wherein the nanoemulsion comprises particles having a polydispersity index of less than about 0.3.

[0032] Embodiment 18: A pouch product configured for oral use, comprising the nanoemulsion according to any one of Embodiments 1 to 17 enclosed in a pouch.

[0033] Embodiment 19: The nanoemulsion according to any one of Embodiments 1 to 18, further comprising a filler, wherein the nanoemulsion is dispersed or disposed in the filler.

[0034] Embodiment 20: A nanoemulsion configured to deliver an active ingredient to a user upon contact with moisture in the user's mouth, the composition comprising oil, water, an emulsifier, and an active ingredient.

[0035] Embodiment 21: A method for preparing a nanoemulsion comprising oil, water, an emulsifier, and an active ingredient, a flavoring material, or a combination thereof, the method comprising high-shear mixing of the oil, water, emulsifier, and active ingredient, flavoring material, or combination thereof.

[0036] Embodiment 22: A nanoemulsion prepared by the method according to Embodiment 21.

[0037] Embodiment 23: A method for stabilizing a flavoring material, an active ingredient, or both, the method comprising providing a nanoemulsion comprising oil, water, an emulsifier, and an active ingredient, flavoring material, or combination thereof, and stabilizing comprising reducing oxidation, evaporation, or both.

[0038] Embodiment 24: A flavor-stabilized product prepared by the method according to Embodiment 23.

[0039] Embodiment 25: An active ingredient-stabilized product prepared by the method according to any one of Embodiments 21 to 24.

[0040] Embodiment 26: A method for dissolving a lipophilic active ingredient, the method comprising providing a nanoemulsion comprising oil, water, an emulsifier, and an active ingredient.

[0041] These features and other features, aspects, and advantageous points of the present disclosure will become apparent from reading the following detailed description in conjunction with the accompanying drawings described explicitly below. The present invention includes any combination of two, three, four, or more of the foregoing embodiments and any combination of two, three, four, or more features or elements described in the present disclosure, regardless of whether such features or elements are explicitly combined in a specific embodiment described herein. The present disclosure is intended to be read as a whole, and in any of its various aspects and embodiments, any separable feature or element of the invention of the present disclosure should be regarded as combinable unless the content is explicitly described otherwise.

[0042] The aspects of the present disclosure are described in the foregoing general terms. Reference is made to the accompanying drawings, which are not necessarily drawn to scale. The figures are merely illustrative and should not be construed as limiting the present disclosure.

Brief Description of the Drawings

[0043]

Figure 1

Modes for Carrying Out the Invention

[0044] The present disclosure provides a nanoemulsion comprising oil, water, an active ingredient and / or a flavoring material, and an emulsifier. Such nanoemulsions are configured for oral use, for example, in a composition encapsulated in a pouch to form a pouch product.

[0045] The present disclosure will be more fully described hereinafter with reference to its exemplary embodiments. These exemplary embodiments are described so that the present disclosure is inclusive and complete and fully conveys the scope of the present disclosure to those skilled in the art. Indeed, the present disclosure can be embodied in many different forms and should not be construed as limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. As used herein and in the claims, the singular forms "a", "an", and "the" include plural references unless the context clearly dictates otherwise. References to "percent dry weight" or "dry weight basis" refer to the weight based on the dry components (i.e., all components excluding water). References to "wet weight" refer to the weight of the composition including water. Unless otherwise indicated, references to "weight percent" of a composition reflect the total wet weight of the composition (i.e., including water).

[0046] A nanoemulsion is a colloidal particulate system having particulate matter in the submicron size range. The particulate matter (also referred to herein as droplets or particles) is generally a solid sphere, and the surface of such particulate matter is negatively charged, amorphous, and lipophilic. A nanoemulsion generally contains nanoscale particles having an average size of less than about 1,000 nm, for example, from about 10 to about 1,000 nm. The nanoemulsions described herein contain nano-particles of oil-in-water emulsions and generally further contain an emulsifier, an active ingredient, and / or a flavoring material. The relative amounts of these various components within the nanoemulsion may vary and are generally selected to impart the desired sensory and performance characteristics to the nanoemulsion. The individual components as examples of the nanoemulsion are described below in this specification.

[0047] Oil Any suitable oil may be used to form the nanoemulsions disclosed herein and includes petroleum-based (e.g., mineral oil) and natural or natural-derived oils (e.g., from plant materials or animal sources). In some embodiments, the oil is a food-grade oil including fractionated oils. Such oils include, but are not limited to, vegetable oils (e.g., acai oil, almond oil, amaranth oil, apricot oil, apple oil, argan oil, avocado oil, babassu oil, beech nut oil, ben oil, bitter gourd oil, black seed oil, blackcurrant oil, borage oil, borneo tallow, cape gooseberry oil, Brazil nut oil, buffalo squash seed oil, buttercup squash seed oil, calodendrum capense oil, canola oil, carob cashew oil, cocoa butter, camellia oil, coconut oil, corn oil, cohune oil, coriander seed oil, cottonseed oil, date seed oil, dikamali oil, egus seed oil, euryale ferox oil, field pennycress oil, flaxseed oil, grape seed oil, grapefruit seed oil, hazelnut oil, hemp oil, kapok oil, kenaf seed oil, laurel oil, lemon oil, linseed oil, macadamia oil, mafura oil, marula oil, meadowfoam oil, mongongo nut oil, mustard oil, neem oil, nutmeg butter, okra seed oil, olive oil, orange oil, palm oil, papaya seed oil, peanut oil, pecan oil, perilla seed oil, persimmon seed oil, pequi oil, pili nut oil, pine nut oil, pistachio oil, pomegranate seed oil, poppy seed oil, plukenetia oil, pumpkin seed oil, quinoa oil, ramtil oil, rapeseed oil, rice bran oil, royle oil, sacha inchi oil, safflower oil, sapote oil, sedge oil, sesame oil, shea butter, soybean oil, sunflower oil, taramira oil, tsubaki oil, thistle oil, tiger nut oil, tobacco seed oil, tomato seed oil, walnut oil, watermelon seed oil, malt oil, and combinations thereof), animal oils (e.g., beef tallow, buffalo fat, mutton fat, goat fat, lard, camel fat, suet, liquid margarine, fish oil, cod liver oil, whale oil, seal oil, and combinations thereof), and mineral oils.

[0048] In some embodiments, the oil includes mineral oil. In some embodiments, the oil includes long-chain fatty acids, monoacylglycerols, diacylglycerols, triacylglycerols, or combinations thereof, where the acyl group is a long-chain fatty acid. As used herein, "long-chain fatty acid" refers to a carboxylic acid (CO2H) having an aliphatic carbon chain of about 11 to about 21 carbon atoms. The aliphatic carbon chain may be straight or branched. The aliphatic carbon chain may be saturated (i.e., having all sp 3 carbon atoms) or unsaturated (i.e., having at least one unsaturation site). As used herein, the term "unsaturated" refers to the presence of one or more carbon-carbon, sp 2 double bonds at one or more positions in the aliphatic carbon chain. The unsaturated alkyl group may be monounsaturated or polyunsaturated. Representative long-chain fatty acids include, but are not limited to, undecylenic acid, undecanoic acid, lauric acid, tridecanoic acid, myristic acid, pentadecanoic acid, palmitic acid, margaric acid, stearic acid, nonadecanoic acid, arachidic acid, heneicosanoic acid, α-linolenic acid, stearidonic acid, eicosapentaenoic acid, cervonic acid, linoleic acid, linolenic acid, γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid.

[0049] In some embodiments, the oil includes acylglycerols such as monoacylglycerols, diacylglycerols or triacylglycerols, where the acyl group is a long-chain fatty acid as described herein. In some embodiments, the oil includes polyunsaturated long-chain fatty acids, or mono-, di-, or triacylglycerols that include polyunsaturated long-chain fatty acids as an acyl component. The chain length of the fatty acids in natural triglycerides may vary, but is generally 16, 18, or 20 carbon atoms. In some embodiments, the polyunsaturated fatty acids (as free fatty acids or, for example, as triglycerides) in the oil may be in the range of about 2% to 100% (w / w), such as about 5% to 100% (w / w) or more than 10% (w / w), for example, 20% to 80% (w / w).

[0050] In some embodiments, the oil includes castor oil, corn oil, coconut oil, cod liver oil, Hypericum perforatum oil, cottonseed oil, palm oil, rice bran oil, sesame oil, rapeseed oil, canola oil, cocoa butter, linseed oil, olive oil, peanut oil, soybean oil, safflower oil, flaxseed oil, sunflower oil, olive oil, or a combination thereof.

[0051] The amount of oil present in the disclosed nanoemulsion may vary, but generally ranges from about 5 wt% to about 80 wt%, or from about 10 wt% to about 60 wt%, or from about 20 wt% to about 50 wt% based on the total weight of the nanoemulsion.

[0052] Water The nanoemulsions disclosed herein include water. The water may be present, for example, as pure water, ultrapure water, physiological saline, buffered physiological saline, or buffered aqueous phase. The water content of the nanoemulsion may be varied according to the desired properties. Generally, the water content is from about 20 to about 90 wt% based on the total weight of the nanoemulsion. In some embodiments, additional hydrophilic water-soluble components may be added to the water, including short-chain mono-, di-, and polyhydric alcohols (e.g., ethanol, benzyl alcohol, glycerol, propylene glycol, propylene carbonate, polyethylene glycol having an average molecular weight of about 200 to about 10,000, diethylene glycol monoethyl ether, and combinations thereof).

[0053] Emulsifier The nanoemulsions disclosed herein contain one or more emulsifiers. An "emulsifier" means a substance that aids in the formation and stabilization of an emulsion by promoting the dispersion of hydrophobic and hydrophilic (e.g., oil and water) components. Generally, an emulsifier is an amphiphilic molecule selected, for example, from nonionic amphiphilic molecules and ionic amphiphilic molecules. The expression "amphiphilic molecule" means any molecule with a dipolar structure that contains at least one hydrophobic portion and at least one hydrophilic portion and has the property of reducing the surface tension of water and the interfacial tension between the water and oil phases. The emulsifiers / amphiphilic molecules provided herein are also referred to, for example, as surfactants and emulsifying agents.

[0054] In some embodiments, the emulsifier contains neutral, positively charged or negatively charged natural or synthetic phospholipid molecules. Phospholipids are composed of two fatty acid tails and a phosphate group head, connected via a third molecule, glycerol. Non-limiting examples of natural phospholipids include soy lecithin, egg lecithin, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidic acid, sphingomyelin, diphosphatidylglycerol, phosphatidylserine, phosphatidylcholine and cardiolipin; synthetic phospholipids including dimyristoyl phosphatidylcholine, dimyristoyl phosphatidylglycerol, distearoyl phosphatidylglycerol and dipalmitoyl phosphatidylcholine; and hydrogenated or partially hydrogenated lecithin and phospholipids. Non-limiting examples of synthetic phospholipid derivatives include phosphatidic acid (DMPA, DPPA, DSPA), phosphatidylcholine (DDPC, DLPC, DMPC, DPPC, DSPC, DOPC, POPC, DEPC), phosphatidylglycerol (DMPG, DPPG, DSPG, POPG), phosphatidylethanolamine (DMPE, DPPE, DSPE DOPE), phosphatidylserine (DOPS), PEG phospholipids (mPEG-phospholipids, polyglycerol-phospholipids, functionalized-phospholipids and end-active phospholipids).

[0055] In some embodiments, the emulsifier includes a surfactant, which may be ionic or non-ionic, and may be hydrophobic or hydrophilic. Examples of hydrophobic surfactants include, but are not limited to, Maisine35-1, Imwitor742, Capmul MCM, Capmul PG12, Lauroglycol90, Lauroglycol FCC, Caproyl90, Captex250, octanoic acid, decanoic acid, undecanoic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, and fatty acids selected from the group consisting of linolenic acid. As used herein, hydrophobic surfactants are also referred to as sparingly water-soluble surfactants or lipophilic surfactants.

[0056] Examples of hydrophilic surfactants include, but are not limited to, polyoxyethylene sorbitan fatty acid esters, hydrogenated castor oil ethoxylates, PEG mono- and di-esters of palmitic acid and stearic acid, fatty acid ethoxylates, and combinations thereof.

[0057] Examples of suitable surfactants generally include, but are not limited to, polyoxyethylene-sorbitan-fatty acid esters; for example, mono- and tri-lauryl, palmityl, stearyl and oleyl esters; for example, the types of products known as polysorbates and marketed under the trade name Tween®; polyoxyethylene fatty acid esters, for example, polyoxyethylene stearate of the types known and marketed under the trade name Myrj®; polyoxyethylene castor oil derivatives, for example, the types of products known and marketed as Cremophor®.Particularly suitable are polyoxyl 35 castor oil (Cremophor® EL) and polyoxyl 40 hydrogenated castor oil (Cremophor® RH40); α-tocopherol, α-tocopheryl polyethylene glycol succinate (vitamin E TPGS), α-tocopherol palmitate and α-tocopherol acetate; PEG glycerol fatty acid esters, for example, PEG-8 glyceryl caprylate / caprate (commercially available under the trade name Labrasol® and known), PEG-4 glyceryl caprylate / caprate (Labrafac Hydro WL1219), PEG-32 glyceryl laurate (Gelucire44 / 14), PEG-6 glyceryl monooleate (Labrafil® M1944CS), PEG-6 glyceryl linoleate (Labrafil® M2125CS); propylene glycol mono- and di-fatty acid esters, for example, propylene glycol laurate, propylene glycol caprylate / caprate; also diethylene glycol monoethyl ether (DGME), commercially available and known as Transcutol® (Gattefosse, Westwood, N.J.); sorbitan fatty acid esters, for example, types known and commercially available under the trade name Span® (e.g., Span85); polyoxyethylene-polyoxypropylene copolymers, for example, types known and commercially available under the name Pluronic® or Poloxamer®; glyceryl triacetate; and monoglycerides and acetylated monoglycerides, for example, glyceryl monodicocoate (Imwitor® 928), glyceryl monocaprylate (Imwitor® 308), and mono- and di-acetylated monoglycerides.

[0058] In some embodiments, the emulsifier is a surfactant, a phospholipid, an amphiphilic polysaccharide, an amphiphilic protein, or a combination thereof. In some embodiments, the emulsifier is an ionic or non-ionic surfactant. In some embodiments, the emulsifier includes Tween20, Tween80, Span20, Span40, Span60, Span80, lecithin, hydrocolloid gum, modified starch, or a combination thereof.

[0059] The concentration of the emulsifier present in the disclosed nanoemulsion may be varied. The concentration of the emulsifier may range from about 0.01 wt% to about 15 wt%, for example, about 0.1 wt% to about 10 wt%, or about 1 wt% to about 5 wt%, based on the total of the nanoemulsion, up to about 15 wt%.

[0060] Stabilizer In some embodiments, the nanoemulsion may further include a stabilizer to assist in retaining the nanoemulsion. Representative examples of suitable types of stabilizers include polysaccharides, polyols, sorbitan esters, glycerol esters, polyethylene glycol esters, block polymers, acrylic polymers (such as Pemulen), silicone-based surfactants, and polysorbates. In some embodiments, the stabilizer is sodium oleate, glycerin, xylitol, sorbitol, ascorbic acid, sodium edetate, sorbitan ester, glycerol monoester, or a combination thereof.

[0061] The concentration of the stabilizer present in the nanoemulsion may be varied. When present, the concentration of the stabilizer may range from about 0.01 wt% to about 10 wt%, for example, about 0.1 wt% to about 5 wt%, or about 0.5 wt% to about 1 wt%, based on the weight of the nanoemulsion, up to about 10 wt%.

[0062] Active ingredient The nanoemulsions disclosed in this specification may contain one or more active ingredients. In some embodiments, two or more active ingredients can be incorporated into the same nanoemulsion. As used herein, "active ingredient" refers to one or more substances belonging to any of the following categories: API (active pharmaceutical ingredient), food additive, natural medicine, and natural substances that can have an effect on humans. Examples of active ingredients include any ingredient known to affect one or more biological functions in the body, such as an ingredient that provides pharmacological activity or has other direct effects on the diagnosis, cure, alleviation, treatment, or prevention of diseases, or an ingredient that affects the structure or any function of the human body (e.g., provides a stimulatory effect on the central nervous system, has an energy effect, antipyretic or analgesic effect, or other useful effects on the body). In some embodiments, the active ingredient may be of the type generally referred to as a dietary supplement, nutritional supplement, "phytochemical", or "functional food". These types of additives provide one or more beneficial biological effects (e.g., health promotion, disease prevention, or other pharmaceutical properties) and may include substances generally available from natural sources (e.g., plant materials) that are not classified or regulated as drugs, as defined in the art.

[0063] Non-limiting examples of active ingredients include plant components (e.g., hemp, lavender, peppermint, eucalyptus, rooibos, fennel, clove, chamomile, basil, rosemary, clove, citrus, ginger, cannabis, ginseng, maca, and chizandra liquid), stimulants (e.g., caffeine or guarana), amino acids (e.g., taurine, theanine, phenylalanine, tyrosine, and tryptophan), vitamins (B6, B12, and C), antioxidants, nicotine components, pharmaceutical components (e.g., nutritional components and pharmaceutical components), cannabinoids (e.g., tetrahydrocannabinol (THC) or cannabidiol (CBD)), and / or components belonging to the category of melatonin. Each of these categories is further described below in this specification. The specific selection of the active ingredient varies depending on the desired flavor, texture, and desired characteristics of the particular product.

[0064] The specific proportion of the active ingredient present in the emulsion of the present disclosure may vary depending on the desired flavor, texture and other characteristics of the nanoemulsion, as well as any product into which the nanoemulsion is incorporated. Generally, the active ingredient or combination thereof is present at a concentration of at least about 0.001% by weight of the nanoemulsion, for example, in the range of 0.001% to about 20%. In some embodiments, the active ingredient is present at a concentration of about 0.1% w / w to about 20% by weight, for example, about 0.1% w / w, about 0.2% by weight, about 0.3% by weight, about 0.4% by weight, about 0.5% by weight, about 0.6% by weight, about 0.7% by weight, about 0.8% by weight or about 0.9% by weight, ~ about 1% by weight, about 2% by weight, about 3% by weight, about 4% by weight, about 5% by weight, about 6% by weight, about 7% by weight, about 8% by weight, about 9% by weight, about 10% by weight, about 11% by weight, about 12% by weight, about 13% by weight, about 14% by weight, about 15% by weight, about 16% by weight, about 17% by weight, about 18% by weight, about 19% by weight, or about 20% by weight, based on the total weight of the nanoemulsion. In some embodiments, the active ingredient 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% by weight to about 10% by weight, or about 1% by weight to about 5% by weight, based on the total weight of the nanoemulsion.

[0065] Plant In some embodiments, the active ingredient comprises a plant component. As used herein, the terms "plant component" or "plant" refer to any plant material or material derived from fungi, and include plant materials in their natural form and plant materials derived from natural plant materials, such as extracts or isolates from plant materials or processed plant materials (e.g., plant materials that have been subjected to heat treatment, fermentation, decolorization or other processing steps that can change the physical and / or chemical properties of the material). For the purposes of the present disclosure, "plants" include, but are not limited to, "herbaceous materials" and refer to seed-producing plants that do not exhibit consistent woody tissue and are often valued for their medicinal or sensory characteristics (e.g., tea or tisane). Referring to a plant material as "non-tobacco" is intended to exclude tobacco materials (i.e., does not include species of the genus Nicotiana).

[0066] When present, the plant is generally at a concentration of about 0.01% w / w to about 10% by weight, such as about 0.01% w / w, about 0.05% by weight, about 0.1% by weight or about 0.5% by weight, ~ about 1% by weight, about 2% by weight, about 3% by weight, about 4% by weight, about 5% by weight, about 6% by weight, about 7% by weight, about 8% by weight, about 9% by weight or about 10% by weight, about 11% by weight, about 12% by weight, about 13% by weight, about 14% by weight, or about 15% by weight, based on the total weight of the composition.

[0067] Plant materials useful in the present disclosure may include any of, but are not limited to, the compounds and sources described herein, mixtures thereof. This type of specific plant material may refer to dietary supplements, dietary supplements, "phytochemicals", or "functional foods". Certain plants as plant materials or extracts thereof have been found to be used in traditional Chinese medicine and are further described herein. Non-limiting examples of plants or plant-derived materials include hemp, eucalyptus, rooibos, fennel, citrus, clove, lavender, peppermint, chamomile, basil, rosemary, ginger, turmeric, green tea, white mulberry, cannabis, cocoa, ashwagandha, baobab, chlorophyll, cordyceps, damiana, ginseng, guarana, and maca. In some embodiments, the composition includes green tea, turmeric, and white berry.

[0068] Ashwagandha (Withania somnifera) is a plant of the Solanaceae (nightshade) family. As a herb, ashwagandha is used in the Indian Ayurvedic system of medicine and is also known as "Indian winter cherry" or "Indian ginseng". In some embodiments, the active ingredient includes ashwagandha.

[0069] The baobab is the common name for a family of deciduous trees of the genus Adansonia. The pulp and seeds of the baobab are generally eaten after drying as food or dietary supplements. In some embodiments, the active ingredient includes the baobab.

[0070] Chlorophyll is any of several related green pigments found in the chloroplasts of algae and plants, as well as in the mesosomes of cyanobacteria. Chlorophyll is used as a food additive (colorant) and dietary supplement. Chlorophyll can be provided from either wild plant material (e.g., plants) or extracts or in the form of a dry powder. In some embodiments, the active ingredient includes chlorophyll.

[0071] The genus Cordyceps is a diverse genus of ascomycete (sac) fungi abundant in temperate humid and tropical forests. Members of the Cordyceps family are widely used in traditional Chinese medicine. In some embodiments, the active ingredient includes Cordyceps.

[0072] Damiana is a small tree of the Passifloraceae family. Damiana is native to South Texas, Central America, Mexico, South America, and the Caribbean. Damiana produces small, fragrant flowers followed by fruits that taste like figs. Extracts from damiana have been found to inhibit aromatase activity, including the isolated compounds pinocembrin and acacetin. In some embodiments, the active ingredient includes damiana.

[0073] Guarana is a vine of the Sapindaceae family native to the Amazon basin. The seeds from the fruits of guarana are about the size of coffee beans and have a high concentration of caffeine and, consequently, stimulant activity. In some embodiments, the active ingredient includes guarana. In some embodiments, the active ingredient includes guarana, honey, and ashwagandha.

[0074] Ginseng is the root of a plant of the genus Panax and is characterized by the presence of unique steroid saponin phytochemicals (ginsenosides) and gintonin. Ginseng is used as a dietary supplement in energy drinks or herbal teas and in traditional medicine. Cultivated species include Korean ginseng (P. ginseng), Chinese ginseng (P. notoginseng), and American ginseng (P. quinquefolius). The types and amounts of the various ginsenosides present in American ginseng and Korean ginseng vary. In some embodiments, the active ingredient includes ginseng. In some embodiments, the ginseng is American ginseng or Korean ginseng. In certain embodiments, the active ingredient includes Korean ginseng.

[0075] Maca is a plant that grows in the central Peruvian highlands of the Andes Mountains. Maca is related to the radish and has an odor similar to that of butterscotch. Maca has been used in traditional (e.g., Chinese) medicine. In some embodiments, the active ingredient includes maca.

[0076] Stimulant 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, vitality, mood, attention, 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 stimulant, analgesic, and anti-inflammatory effects. The stimulants of the present invention may be natural, natural-derived, or fully synthetic. For example, certain plant materials (such as guarana, tea, coffee, cocoa, etc.) may have the effects of stimulants due to the presence of, for example, caffeine or related alkaloids, and thus are "natural" stimulants. "Natural-derived" means that the stimulant (for example, caffeine, theacrine) is in a purified form and outside its natural (for example, plant) matrix. For example, caffeine can be obtained by extraction and purification from a plant source (such as tea). "Fully synthetic" means that the stimulant is obtained by chemical synthesis.

[0077] When present, the stimulant or combination of stimulants (for example, caffeine, theacrine, and combinations thereof) is generally in a concentration of about 0.1% w / w to about 15% by weight, for example, about 0.1% w / w, about 0.2% by weight, about 0.3% by weight, about 0.4% by weight, about 0.5% by weight, about 0.6% by weight, about 0.7% by weight, about 0.8% by weight, or about 0.9% by weight, ~ about 1% by weight, about 2% by weight, about 3% by weight, about 4% by weight, about 5% by weight, about 6% by weight, about 7% by weight, about 8% by weight, about 9% by weight, about 10% by weight, about 11% by weight, about 12% by weight, about 13% by weight, about 14% by weight, or about 15% by weight, based on the total weight of the composition.

[0078] 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.

[0079] Amino acid In some embodiments, the active ingredient comprises an amino acid. As used herein, the term "amino acid" refers to an organic compound containing an amine (-NH2), and a carboxyl (-COOH) or sulfonic acid (SO3H) functional group, along with the side chain (R group) specific to each amino acid. The amino acid may be proteinogenic or non-proteinogenic. "Proteinogenic" means that the amino acid is one of the 20 natural amino acids found in proteins. Examples of proteinogenic amino acids include alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. "Non-proteinogenic" means that the amino acid is either not naturally found in proteins or is not directly produced by cellular machinery (e.g., is a product of post-translational modification). Non-limiting examples of non-proteinogenic amino acids include gamma-aminobutyric acid (GABA), taurine (2-aminoethanesulfonic acid), theanine (L-γ-glutamylethylamide), hydroxyproline, and beta-alanine.

[0080] When present, the amino acid or combination of amino acids (e.g., taurine, theanine, and combinations thereof) is generally in a concentration of about 0.1% w / w to about 15% by weight, based on the total weight of the composition, such as about 0.1% w / w, about 0.2% by weight, about 0.3% by weight, about 0.4% by weight, about 0.5% by weight, about 0.6% by weight, about 0.7% by weight, about 0.8% by weight, or about 0.9% by weight, to about 1% by weight, about 2% by weight, about 3% by weight, about 4% by weight, about 5% by weight, about 6% by weight, about 7% by weight, about 8% by weight, about 9% by weight, about 10% by weight, about 11% by weight, about 12% by weight, about 13% by weight, about 14% by weight, or about 15% by weight.

[0081] 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.

[0082] Vitamin In some embodiments, the active ingredient comprises a vitamin or a combination of vitamins. As used herein, the term "vitamin" refers to an organic molecule (or related group of molecules) that is an essential micronutrient required for proper functioning of metabolism in mammals. There are 13 vitamins required by human metabolism, vitamin A (all-trans retinol, all-trans retinyl esters, as well as 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 (quinone).

[0083] If present, the vitamin or combination of vitamins (e.g., vitamin B6, vitamin B12, vitamin E, vitamin C, or combinations thereof) is generally in a concentration of about 0.01% w / w to about 6% by weight, such as about 0.01% by weight, about 0.02% by weight, about 0.03% by weight, about 0.04% by weight, about 0.05% by weight, about 0.06% by weight, about 0.07% by weight, about 0.08% by weight, about 0.09% by weight, or about 0.1% by weight, ~ about 0.2% by weight, about 0.3% by weight, about 0.4% by weight, about 0.5% by weight, about 0.6% by weight, about 0.7% by weight, about 0.8% by weight, about 0.9% by weight, or about 1% by weight, based on the total weight of the composition.

[0084] In some embodiments, the vitamin is vitamin B6, vitamin B12, vitamin E, vitamin C or combinations thereof. In some embodiments, the active ingredient comprises a combination of vitamin B6, caffeine and theanine. In some embodiments, the active ingredient comprises a combination of vitamin B6, vitamin B12 and taurine. In some embodiments, the active ingredient comprises a combination of vitamin B6, vitamin B12, ginseng and theanine. In some embodiments, the active ingredient comprises a combination of vitamin C, baobab and chlorophyll.

[0085] Antioxidant In some embodiments, the active ingredient comprises one or more antioxidants. As used herein, the term "antioxidant" refers to a substance that can prevent or inhibit oxidation by stopping the reaction of free radicals and can slow down or prevent some types of cell damage. Antioxidants can be natural or synthetic. Natural antioxidants include those found in foods and plant materials. Non-limiting examples of antioxidants include certain plant materials, vitamins, polyphenols, and phenolic derivatives.

[0086] Examples of plant materials related to the characteristics of antioxidants include, but are not limited to, acai berry, alfalfa, allspice, annatto seed, apricot oil, basil, bergamot, wild bergamot, black pepper, blueberry, borage oil, bugleweed, cocoa, calamust root, catnip, cat's claw, cayenne pepper, chaga mushroom, chervil, cinnamon, dark chocolate, potato peel, grape seed, ginseng, ginkgo, St. John's wort, saw palmetto, green tea, black tea, black cohosh, cayenne, chamomile, clove, cocoa powder, cranberry, dandelion, grapefruit, honeybush, echinacea, garlic, evening primrose, Japanese aster, ginger, goldenseal, hawthorn, hibiscus flower, amacha tsuru, cabbage, lavender, licorice, marjoram, greater burdock, mint (menthe), oolong tea, beetroot, orange, oregano, papaya, pennyroyal, peppermint, red clover, rooibos (red or green), rose hip, rosemary, sage, clary sage, savory, spearmint, spirulina, slippery elm bark, high tannin sorghum, high tannin sorghum grains, sumac bran, comfrey leaf and root, goji berry, gotu kola, thyme, turmeric, uva ursi, urushi, valerian, wild yam root, wintergreen, yacon root, yellow dock, yerba mate, yerba santa, bacopa monnieri, withania somnifera, lion's mane mushroom, and silybum marianum. Such plant materials may be provided in fresh or dried form, as essential oils, or in the form of extracts. Plant materials (and their extracts) often contain compounds from various classes known to have antioxidant effects, such as minerals, vitamins, isoflavones, phytosterols, allyl sulfides, dithiothiones, isothiocyanates, indoles, lignans, flavonoids, polyphenols, and carotenoids.Examples of compounds found in plant extracts or oils include ascorbic acid, peanut hulls, resveratrol, sulforaphane, beta-carotene, lycopene, lutein, coenzyme Q, carnitine, quercetin, kaempferol, etc. For example, see Santhosh et al., Phytomedicine, 12(2005)216-220, which is incorporated herein by reference.

[0087] Non-limiting examples of other suitable antioxidants include citric acid, vitamin E or its derivatives, tocopherol, epicatechol, epigallocatechol, epigallocatechin gallate, erythorbic acid, sodium erythorbate, 4-hexylresorcinol, theaflavin, theaflavin monogallate A or B, theaflavin digallate, phenolic acids, glycosides, quercitrin, isoquercitrin, hyperoside, 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 its derivatives, flavonoids, polyphenols, carotenoids, or combinations thereof.

[0088] When present, the antioxidant is generally in a concentration of about 0.001% w / w to about 10% by weight, based on the total weight of the composition, such as about 0.001%, about 0.005%, about 0.01% w / w, about 0.05%, about 0.1% or about 0.5%, ~ about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%.

[0089] Cannabinoid In some embodiments, the active ingredient comprises one or more cannabinoids. As used herein, the term "cannabinoid" refers to a class of diverse chemical compounds that act on cannabinoid receptors, also known as the endocannabinoid system, in cells that alter the release of neurotransmitters in the brain. Ligands for these receptor proteins include endocannabinoids that are naturally produced in the body by animals, phytocannabinoids found in cannabis, and synthetic cannabinoids that are artificially manufactured. Examples of cannabinoids found in cannabis include, but are not limited to, cannabigerol (CBG), cannabinchromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), cannabinodiol (CBDL), cannabinocyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidiovalerate (CBDV), cannabinchromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabinotriol (CBO), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabivarinic acid (THCV A). In certain embodiments, the cannabinoid is selected from tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, and cannabidiol (CBD), another major component of the plant that lacks psychoactivity. All of the aforementioned compounds can be used in isolated form from plant material or in synthetically derived form.

[0090] Alternatively, the active ingredient may be a cannabis analog, which is a class of compounds derived from plants other than cannabis that have biological effects on the endocannabinoid system similar to cannabinoids. Examples include yangonin, α-amyrin or β-amyrin (also classified as terpenes), cyanidin, curcumin (turmeric), catechin, quercetin, salvianolic acid A, N-acylethanolamine, and N-alkylamide lipids.

[0091] When present, cannabinoids (e.g., CBD) or cannabis analogs are generally at least about 0.1% by weight of the composition, based on the total weight of the composition, for example, in the range of about 0.1% to about 30% by weight, such as 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, ~ about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 15%, about 20%, or about 30% by weight.

[0092] Terpenes The active ingredients suitable for use in the present disclosure can also be classified as terpenes, many of which are related to biological effects such as sedative effects. Terpenes have the general formula (C5H8) n and are understood to include monoterpenes, sesquiterpenes, and diterpenes. Terpenes can have an acyclic, monocyclic, or bicyclic structure. Some terpenes, when used in combination with cannabinoids or cannabis analogs, produce an entourage effect. Examples include β-caryophyllene, linalool, limonene, β-citronellol, linalyl acetate, pinene (α or β), geraniol, carvone, eucalyptol, menthone, iso-menthone, piperitone, myrcene, β-bulbonene, and germacrene, and they can be used alone or in combination.

[0093] Pharmaceutical ingredients The pharmaceutical ingredient can be any known agent adapted for therapeutic, prophylactic, or diagnostic use. The pharmaceutical ingredient can include, for example, synthetic organic compounds, proteins and peptides, polysaccharides and other sugars, lipids, inorganic compounds, and nucleic acid sequences, and have therapeutic, prophylactic, or diagnostic activity. Non-limiting examples of pharmaceutical ingredients include analgesics and antipyretics (e.g., acetylsalicylic acid, acetaminophen, 3-(4-isobutylphenyl)propanoic acid).

[0094] Nicotine component In certain embodiments, the nicotine component may be included in the nanoemulsion. The "nicotine component" means any suitable form of nicotine (e.g., free base or salt) for oral absorption of at least a portion of the nicotine present. Generally, the nicotine component is selected from the group consisting of nicotine free base and nicotine salts. In some embodiments, the nicotine is in its free base form and can, for example, be readily absorbed into a microcrystalline cellulose material to form a microcrystalline cellulose nicotine carrier complex. See, for example, the discussion of nicotine in free base form in U.S. Patent Publication No. 2004 / 0191322 (Hansson), which is incorporated herein by reference. Thus, in some embodiments, a nanoemulsion comprising an MCC-nicotine carrier complex is provided.

[0095] In some embodiments, at least a portion of the nicotine can be used in the form of a salt. The salts of nicotine can be provided using the types of components and techniques described in U.S. Patent No. 2,033,909 (Cox et al.) and Perfetti, Beitrage Tabakforschung Int., 12:43-54 (1983), each of which is incorporated herein by reference. Further salts are disclosed, for example, in U.S. Patent No. 9,738,622 (Dull et al.) and U.S. Patent Publications No. 2018 / 0230126 (Dull et al.), 2016 / 0185750 (Dull et al.) and 2018 / 0051002 (Dull et al.), each of which is incorporated herein by reference. Additionally, the salts of nicotine can be obtained from sources such as Pfaltz and Bauer, Inc. and K&K Laboratories, Division of ICN Biochemicals, Inc. Generally, the nicotine component is selected from the group consisting of nicotine free base, hydrochlorides, dihydrochlorides, monotartrates, ditartrates, sulfates, salicylates, and nicotine salts such as zinc chloride nicotinate.

[0096] In some embodiments, at least a portion of the nicotine may be in the form of a resin complex of nicotine, and the nicotine is nicotine such as nicotinopolaricrex bound to an ion exchange resin, for example, polymethacrylic acid, such as Amberlite IRP64, Purolite C115HMR or Doshion P551. See, for example, U.S. Patent No. 3,901,248 (Lichtneckert et al.) (incorporated herein by reference). Another example is a nicotine polyacrylic carbomer complex such as Carbopol 974P. In some embodiments, the nicotine may be present in the form of a nicotine polyacrylic complex.

[0097] Generally, the nicotine component (calculated as the free base), when present, is in the range of at least about 0.001% by weight of the nanoemulsion, for example, from about 0.001% to about 10%. In some embodiments, the nicotine component is calculated as the free base and is present at a concentration of about 0.1% w / w to about 10% by weight, for example 0.1% w / w, about 0.2% by weight, about 0.3% by weight, about 0.4% by weight, about 0.5% by weight, about 0.6% by weight, about 0.7% by weight, about 0.8% by weight or about 0.9% by weight, ~ about 1% by weight, about 2% by weight, about 3% by weight, about 4% by weight, about 5% by weight, about 6% by weight, about 7% by weight, about 8% by weight, about 9% by weight, or about 10% by weight, based on the total weight of the nanoemulsion. In some embodiments, the nicotine component is calculated as the free base and is present at a concentration of about 0.1% w / w to about 3% by weight, for example, from about 0.1% w / w to about 2.5% by weight, from about 0.1% to about 2.0% by weight, from about 0.1% w / w to about 1.5% by weight, or from about 0.1% w / w to about 1% by weight. These ranges can also be applied to other active ingredients described herein.

[0098] In some embodiments, the nanoemulsion of the present disclosure may be characterized by containing no or substantially no nicotine. For example, certain embodiments may be characterized by having a nicotine component of less than 0.1 wt%, or less than 0.01 wt%, or less than 0.001 wt%, or 0 wt% nicotine component.

[0099] In some embodiments, the active ingredient is lipophilic (i.e., having much greater solubility in the oil phase relative to the aqueous phase). Without wishing to be bound by theory, formulating a lipophilic active ingredient as a nanoemulsion can enhance the stability of the active ingredient (e.g., against oxidation). The nanoemulsion has small droplets with a larger surface area and potentially can aid in enhancing oral or mucosal absorption of the active ingredient, solubilizing the active ingredient, and / or masking the taste of the active ingredient.

[0100] In certain embodiments, the active ingredient is selected from caffeine, taurine, GABA, theanine, vitamin C, lemon balm extract, ginseng, choline, sunflower lecithin, and combinations thereof. For example, the active ingredient may comprise a combination of caffeine, theanine, and optionally ginseng. In another embodiment, the active ingredient comprises a combination of theanine, gamma-aminobutyric acid (GABA), and lemon balm extract. In a further embodiment, the active ingredient comprises theanine, theanine, and tryptophan or theanine and one or more B vitamins (e.g., vitamin B6 or B12). In a further embodiment, the active ingredient comprises a combination of caffeine, taurine, and vitamin C.

[0101] Flavoring agent In some embodiments, the nanoemulsion contains flavor materials. As used herein, "flavor material" or "flavorant" is any fragrant or aromatic substance that can change the sensory characteristics associated with the nanoemulsion and / or an oral product incorporating such a nanoemulsion. Examples of sensory characteristics that can be altered by flavorants include taste, texture, moistness, coolness / warmth, and / or fragrance / aroma. The flavorants can be natural or synthetic, and the flavor characteristics imparted thereby are described, but not limited to, as fresh, sweet, herbal, confectionery, floral, fruity, or spicy. Specific types of flavorants include, but are not limited to, vanilla, coffee, chocolate / cocoa, cream, mint, spearmint, menthol, peppermint, wintergreen, eucalyptus, lavender, cardamom, nutmeg, cinnamon, clove, cascarilla, sandalwood, honey, jasmine, ginger, anise, sage, licorice, lemon, orange, apple, peach, lime, cherry, strawberry, trigeminal sensory agents, terpenes, and any combination thereof. See also Leffingwell et al., Tobacco Flavoring for Smoking Products, R. J. Reynolds Tobacco Company (1972), which is incorporated herein by reference. The flavorants may also include components that are considered to be wetting agents, cooling agents, or smoothing agents, such as eucalyptus. These flavorants may be provided neat (i.e., alone) or in a complex, and may be used as concentrates or flavor 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 (White et al.), U.S. Patent Application Publication No. 2005 / 0244521 (Strickland et al.), and PCT Application Publication No. WO05 / 041699 (Quinter et al.), each of which is incorporated herein by reference. In some examples, the flavorants may be provided in spray-dried form or in liquid form.

[0102] In some embodiments, the flavoring material is lipophilic. Without wishing to be bound by theory, a formulation of a lipophilic flavoring material as a nanoemulsion can enhance the stability of the flavoring material (e.g., against oxidation or evaporation). In some embodiments, the flavoring material is oxidizable, which means that when exposed to air, the components of the flavoring material are denatured by chemical changes. Examples of functional groups that may be present in oxidizable flavoring material components include, but are not limited to, alkenes, aldehydes, and / or ketones. In some embodiments, the flavoring material includes citrus oil. Citrus oil contains terpene components that are prone to oxidation, evaporation, or both, and thus can benefit from being included in a product, particularly in the form of the nanoemulsions provided herein.

[0103] The amount of flavoring material useful in the nanoemulsion can vary, but is generally up to 10% by weight, and certain embodiments feature a flavoring content of at least about 0.1% by weight, such as about 0.5% to about 10% by weight, about 1% to about 6% by weight, or about 2% to about 5% by weight, based on the total weight of the nanoemulsion.

[0104] Additional Components In some embodiments, the nanoemulsions disclosed herein may further include additional components and / or the nanoemulsions may be combined with additional components to form a composition configured for oral use. The additional components may include one or more buffering agents, colorants, salts, sweeteners, fillers, binders, wetting agents, tobacco materials, oral care additives, other additives, or combinations thereof. Each of these additional components is further described below in this specification.

[0105] Salt In some embodiments, the nanoemulsion or composition comprising the nanoemulsion described in the present disclosure contains a salt (e.g., an alkali metal salt), and is generally used in an amount sufficient to provide the desired sensory attributes to the composition. Non-limiting examples of suitable salts include sodium chloride, potassium chloride, ammonium chloride, wheat flour salt, sodium acetate, sodium citrate, and the like. When present, a representative amount of the salt is about 0.5 wt% or more, about 1.0 wt% or more, or about 1.5 wt% or more, but is about 10% or less, or about 7.5% or less, or about 5% or less (about 0.5 to about 5 wt%) of the total weight of the nanoemulsion or the composition comprising the nanoemulsion.

[0106] Sweetener To improve the sensory properties of the nanoemulsion or composition comprising the nanoemulsion described in the present disclosure, one or more sweeteners may be added. The sweetener may be any sweetener or combination of sweeteners in natural or artificial form, or a combination of natural and artificial sweeteners. Examples of natural sweeteners include fructose, sucrose, glucose, maltose, isomaltulose, mannose, galactose, lactose, stevia, honey, and the like. Examples of artificial sweeteners include sucralose, maltodextrin, saccharin, aspartame, acesulfame K, neotame, and the like. In some embodiments, the sweetener comprises one or more sugar alcohols. A sugar alcohol is a polyol derived from a monosaccharide or disaccharide having a partially or fully hydrogenated form. The sugar alcohol has, for example, about 4 to about 20 carbon atoms and includes erythritol, arabinitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and combinations thereof (e.g., hydrogenated starch hydrolysates).

[0107] If present, the sweetener or combination of sweeteners may be present in an amount of about 0.1 to about 20 wt% or more, for example, about 0.1 to about 1 wt%, about 1 to about 5 wt%, about 5 to about 10 wt%, or about 10 to about 20 wt% based on the total weight of the nanoemulsion or composition comprising the nanoemulsion.

[0108] Buffer In certain embodiments, the nanoemulsion or composition comprising the nanoemulsion of the present disclosure may include a pH adjuster or buffer. Examples of pH adjusters and buffers that can be used include, but are not limited to, metal hydroxides (e.g., alkali metal hydroxides such as sodium hydroxide and potassium hydroxide), and other alkali metal buffers such as metal carbonates (e.g., potassium carbonate or sodium carbonate) or metal bicarbonates such as sodium bicarbonate. If present, the buffer is generally present in an amount of less than about 5 wt%, for example, about 0.5 to about 5 wt%, for example, about 0.75 to about 4 wt%, about 0.75 to about 3 wt%, or about 1 to about 2 wt% based on the weight of the nanoemulsion or composition comprising the nanoemulsion. Non-limiting examples of suitable buffers include alkali metal acetates, glycineates, phosphates, glycerophosphates, citrates, carbonates, bicarbonates, borates, or mixtures thereof.

[0109] Colorant The colorant may be used in an amount sufficient to impart the desired physical attributes to the nanoemulsion or composition comprising the nanoemulsion described in the present disclosure. Examples of colorants include various dyes and pigments, such as caramel color and titanium dioxide. The amount of colorant useful in the nanoemulsion or composition comprising the nanoemulsion can vary, but if present, it is generally up to about 3 wt%, for example, about 0.1 wt%, about 0.5 wt%, or about 1 wt% to about 3 wt% based on the total weight of the nanoemulsion or composition comprising the nanoemulsion.

[0110] Oral care ingredient Oral care ingredients provide the ability to suppress tooth decay or tooth loss, suppress gum diseases, relieve mouth pain, whiten teeth or otherwise suppress tooth discoloration, induce salivary stimulation, suppress bad breath, refresh breath, etc. For example, an effective amount of ingredients such as thyme oil, eucalyptus oil, and zinc (such as the ingredients of a formulation commercially available as ZYTEX® from Discus Dental) can be incorporated into the nanoemulsion or composition containing the nanoemulsion described herein. Other examples of ingredients that can be incorporated into the nanoemulsion or composition containing the nanoemulsion of the present invention in a desired effective amount include those incorporated into the types of oral care compositions described in Takahashi et al., Oral Microbiology and Immunology, 19(1), 61-64 (2004); U.S. Patent No. 6,083,527 (Thistle) and U.S. Patent Application Publication Nos. 2006 / 0210488 (Jakubowski) and 2006 / 02228308 (Cummins et al.). Other exemplary ingredients include those contained in formulations commercially available as MALTISORB® from Roquette and DENTIZYME® from NatraRx. When these ingredients are present, a typical amount of the oral care additive is at least about 1%, often at least about 3%, and frequently at least about 5% of the total weight of the nanoemulsion or composition containing the nanoemulsion. The amount of the oral care additive generally does not exceed about 30%, often does not exceed about 25%, and frequently does not exceed about 20% of the total weight of the nanoemulsion or composition containing the nanoemulsion.

[0111] Filler The composition containing the nanoemulsion described in this specification may contain a filler. The nanoemulsions disclosed herein can be combined with fillers in various ways (i.e., in the composition containing the nanoemulsion disclosed herein). For example, the nanoemulsion may be disposed on the surface of the filler, dispersed or impregnated in the filler (e.g., adsorbed or absorbed), or the filler and the nanoemulsion may be present in an oral product without being physically combined or without physical contact (e.g., the filler and the nanoemulsion may be provided separately and independently in the same product). The filler may satisfy multiple functions such as increasing sensory acceptance characteristics such as texture and mouthfeel, or increasing the adhesiveness or compressibility of the product, depending on the product and the combination of the filler and the nanoemulsion. Generally, the filler is a porous granular material and is cellulose-based. For example, the filler is any non-tobacco plant material or a derivative thereof and includes cellulose materials derived from such sources. Examples of cellulose non-tobacco plant materials include cereal grains (e.g., corn, oats, barley, rye, buckwheat, etc.), sugar beets (e.g., FIBREX® brand filler available from International Fiber Corporation), bran fibers, and mixtures thereof. Non-limiting examples of derivatives of non-tobacco plant materials include starches (e.g., derived from potatoes, wheat, rice, corn), natural cellulose, and modified cellulose materials. Additional examples of potential fillers include maltodextrin, dextrose, calcium carbonate, calcium phosphate, lactic acid, mannitol, xylitol, and sorbitol. Combinations of fillers can also be used.

[0112] As used herein, "starch" may refer to pure starch, modified starch, or starch derivatives from any source. Starch is generally present in granular form in almost all green plants and various types of plant tissues and organs (e.g., seeds, leaves, rhizomes, roots, tubers, shoots, fruits, kernels, and stems). Starch can vary in composition as well as in granular form and particle size. Starches from different sources often have different chemical and physical characteristics. Certain starches can be selected for inclusion in a composition based on the ability of the starch material to impart certain sensory acceptance characteristics to the composition. Starches from various species can be used. For example, major sources of starch include cereal grains (e.g., rice, wheat, and corn) and root vegetables (e.g., potato and cassava). Other examples of starch sources include acorn, arrowroot, aracacha, banana, barley, beans (e.g., navy bean, mung bean, green bean, pea, chickpea), breadnut, buckwheat, canna, chestnut, colocasia, katakuri, kudzu, malanga, millet, oats, oca, Polynesian arrowroot, sago, sorghum, sweet potato, quinoa, rye, tapioca, taro, tobacco, shirogwa, and yam. Certain starches are modified starches. Modified starches have undergone one or more structural modifications and are often designed to change their high-temperature properties. Some starches have been developed by genetic modification and are considered "genetically modified" starches. Other starches are obtained and subsequently modified by chemical, enzymatic, or physical means. For example, modified starches may be starches that have been subjected to chemical reactions such as esterification, etherification, oxidation, acid-catalyzed depolymerization (thinning), or oxidation in the presence of a base, decolorization, sugar transfer, and depolymerization (e.g., dextrinization in the presence of a catalyst), crosslinking, acetylation, hydroxypropylation, and / or partial hydrolysis. Enzymatic treatment involves subjecting natural starch to an enzyme isolate or concentrate, a microbial enzyme, and / or an enzyme natural to a plant material, such as the amylase present in corn kernels, to modify the corn starch.

[0113] Other starches are modified by heat treatment, such as gelatinization, dextrinization, and / or cold water swelling processes. Specific modified starches include phosphorylated starch, phosphate cross-linked starch, phosphate cross-linked starch esterified with sodium trimetaphosphate, phosphate cross-linked starch phosphate, acetylated phosphate cross-linked starch, starch acetate esterified with acetic anhydride, starch acetate esterified with vinyl acetate, acetylated adipic acid cross-linked starch, acetylated glycerol cross-linked starch, hydroxypropyl starch, hydroxypropyl glycerol cross-linked starch, and sodium octenyl succinate starch.

[0114] In some embodiments, the filler is a cellulose material or a cellulose derivative. One filler particularly suitable for use in the compositions described herein is microcrystalline cellulose (“MCC”). MCC may be synthetic or semi-synthetic and can be obtained entirely from natural cellulose. MCC is selected from the group consisting of AVICEL® grades PH-100, PH-102, PH-103, PH-105, PH-112, PH-113, PH-200, PH-300, PH-302, VIVACEL® grades 101, 102, 12, 20 and EMOCEL® grades 50M and 90M, and mixtures thereof. In one embodiment, the composition comprises MCC as a filler.

[0115] The amount of filler may be varied, but when present, it is generally up to about 75% by weight of the composition containing the nanoemulsion, based on the total weight of the composition. The general range of filler (e.g., MCC) in the composition is from about 10 to about 75% by weight of the total weight of the composition, and may be, for example, about 10% by weight, about 15% by weight, about 20% by weight, about 25% by weight, or about 30% by weight, ~ about 35% by weight, about 40% by weight, about 45% by weight, or about 50% by weight (e.g., about 20 to about 50% by weight or about 25 to about 45% by weight). In certain embodiments, the amount of filler is at least about 10% by weight, such as at least about 20% by weight or at least about 25% by weight or at least about 30% by weight, or at least 35% by weight, or at least 40% by weight, based on the total weight of the composition.

[0116] Binder The binder (or combination of binders) may be used in an amount sufficient to impart the desired physical attributes and physical integrity to the composition in certain embodiments, and the binder also often functions as a thickening or gelling agent. Common binders may be organic or inorganic, or combinations thereof. Representative binders include cellulose derivatives (e.g., cellulose ethers), povidone, sodium alginate, starch-based binders, pectin, gums, carrageenan, pullulan, zein, and combinations thereof. In some embodiments, the binder comprises pectin or carrageenan, or a combination thereof.

[0117] The amount of binder useful in the composition can be varied, but is generally up to 30% by weight, and certain embodiments are characterized by a binder content of at least about 0.1% by weight, such as about 1% to about 30% by weight, or about 5% to about 10% by weight, based on the total weight of the composition.

[0118] In one embodiment, the binder includes a cellulose derivative. In certain embodiments, the cellulose derivative is a cellulose ether (including carboxyalkyl ether), which means a cellulose polymer in which the hydrogen of one or more hydroxyl groups in the cellulose structure is substituted with an alkyl, hydroxyalkyl, or aryl group. Non-limiting examples of such cellulose derivatives include methylcellulose, hydroxypropyl cellulose ("HPC"), hydroxypropyl methylcellulose ("HPMC"), hydroxyethyl cellulose, and carboxymethyl cellulose ("CMC"). In one embodiment, the cellulose derivative is one or more of methylcellulose, HPC, HPMC, hydroxyethyl cellulose, and CMC. In one embodiment, the cellulose derivative is HPC. In one embodiment, the cellulose derivative is a combination of HPC and HPMC. In some embodiments, the composition includes about 1 to about 10% by weight of the cellulose derivative based on the total weight of the composition, and in certain embodiments, about 1 to about 5% by weight of the cellulose derivative of the composition, for example, about 1%, about 2%, or about 3%, ~ about 4%, or about 5% by weight of the composition.

[0119] In certain embodiments, the binder includes a gum, such as a natural gum. As used herein, a natural gum refers to a naturally derived polysaccharide material having binding properties that are also useful as a thickening or gelling agent. Representative natural gums derived from plants are generally somewhat water-soluble and include xanthan gum, guar gum, gum arabic, gatti gum, tragacanth gum, karaya gum, locust bean gum, gellan gum, and combinations thereof. When present, the natural gum binder material is generally present in an amount of about 5% by weight, for example, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, or about 1% by weight, ~ about 2%, about 3%, about 4%, or about 5% by weight based on the total weight of the composition.

[0120] Wetting agent In certain embodiments, the one or more wetting agents may be used in the compositions comprising the nanoemulsions of the present disclosure and examples of wetting agents include, but are not limited to, glycerin, propylene glycol, and the like. When a wetting agent is included, the lubricant is generally provided in an amount sufficient to impart the desired wetting attributes to the composition. Further, in some examples, the wetting agent can impart the desired flow characteristics to the composition for casting into a mold. When present, the wetting agent is generally made at about 5 wt% or less (e.g., about 0.5 wt% to about 5 wt%) of the weight of the composition. When present, representative amounts of the wetting agent are about 0.1 wt% to about 1 wt% or about 1 wt% to about 5 wt% based on the total weight of the composition.

[0121] Tobacco material In some embodiments, the nanoemulsion of the present disclosure or a composition containing the nanoemulsion may include a tobacco material. The tobacco material may vary in species, type, and form. Generally, the tobacco material is obtained from harvested plants of the Nicotiana genus. Examples of Nicotiana species include N. tabacum, N. rustica, N. alata, N. arentsii, N. excelsior, N. forgetiana, N. glauca, N. glutinosa, N. gossei, N. kawakamii, N. knightiana, N. langsdorffi, N. otophora, N. setchelli, N. sylvestris, N. tomentosa, N. tomentosiformis, N. undulata, N. x sanderae, N. africana, N. amplexicaulis, N. benavidesii, N. bonariensis, N. debneyi, N. longiflora, N. maritina, N. megalosiphon, N. occidentalis, N. paniculata, N. plumbaginifolia, N. raimondii, N. rosulata, N. simulans, N. stocktonii, N. suaveolens, N. umbratica, N. velutina, N. wigandioides, N. acaulis, N.acaulis), N. acuminata, N. 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., Hersperis, N. pauciflora, N. petunioides, N. quadrivalvis, N. repanda, N. rotundifolia, N. solanifolia, and N. spegazzinii. Various other representative types of plants derived from Nicotiana species are described in Goodspeed, The Genus Nicotiana, (Chonica Botanica)(1954), U.S. Patent Nos. 4,660,577 (Sensabaugh, Jr. et al.), 5,387,416 (White et al.), 7,025,066 (Lawson et al.), 7,798,153 (Lawrence, Jr.), and 8,186,360 (Marshall et al.), each of which is incorporated herein by reference. Descriptions of various tobacco types, growing practices, and harvesting practices are described in Tobacco Production, Chemistry and Technology, Davis et al., (Eds.)(1999), which is incorporated herein by reference.

[0122] Nicotiana species that can yield suitable tobacco materials can be produced using genetic modification or hybridization techniques (e.g., tobacco plants can generally be genetically modified or hybridized to increase or decrease the production of components, characteristics, or attributes). See, for example, the types of genetic modification of plants described in U.S. Patent Nos. 5,539,093 (Fitzmaurice et al.), 5,668,295 (Wahab et al.), 5,705,624 (Fitzmaurice et al.), 5,844,119 (Weigl), 6,730,832 (Dominguez et al.), 7,173,170 (Liu et al.), 7,208,659 (Colliver et al.), 7,230,160 (Benning et al.), U.S. Patent Application Publication No. 2006 / 0236434 (Conkling et al.), and PCTWO2008 / 103935 (Nielsen et al.). Also see the types of tobacco described in U.S. Patent Nos. 4,660,577 (Sensabaugh, Jr. et al.), 5,387,416 (White et al.), and 6,730,832 (Dominguez et al.) (each incorporated herein by reference).

[0123] In some embodiments, Nicotiana species can be selected for the content of various compounds present herein. For example, plants can be selected based on these plants producing relatively large amounts of one or more of the desired compounds isolated from the plant. In certain embodiments, plants of the Nicotiana species (e.g., Galpao commun tobacco) grow particularly for abundant leaf surface compounds. Tobacco plants can be grown in a greenhouse, a growth chamber, or in the field, or can be grown hydroponically.

[0124] Various parts or portions of plants of the genus Nicotiana may be included in the nanoemulsions or compositions disclosed herein. For example, substantially all of the plant (e.g., the whole plant) can be harvested and used as well. Alternatively, various parts or species of the plant can be harvested or separated for further use after harvesting. For example, flowers, leaves, stems, trunks, roots, seeds, and various combinations thereof can be isolated for further use or processing. In some embodiments, the tobacco material includes tobacco leaves (leaf pieces). The nanoemulsions or compositions disclosed herein may include processed tobacco parts or pieces, cured and aged tobacco in essentially the form of natural leaf pieces and / or stems, tobacco extracts, extracted tobacco pulp (e.g., using water as a solvent), or mixtures of the foregoing (e.g., a mixture combining extracted tobacco pulp and granular cured and aged natural tobacco leaf pieces).

[0125] In certain embodiments, the tobacco material includes a solid tobacco material selected from the group consisting of leaf pieces and stems. The tobacco used in the mixture most preferably includes tobacco leaf pieces or a mixture of tobacco leaf pieces and stems (at least a portion of which has been smoked). The tobacco portion in the mixture may have a processed form, e.g., a processed tobacco stem (e.g., a cut roll stem, a cut roll expanded stem, or a cut puff stem) or puffed tobacco (e.g., puffed tobacco such as dry ice expanded tobacco (DIET)). See, for example, the tobacco puffing processes described in U.S. Patent Nos. 4,340,073 (de la Burde et al.), 5,259,403 (Guy et al.), 5,908,032 (Poindexter et al.), and 7,556,047 (Poindexter et al.) (all incorporated herein by reference). Further, the composition may optionally incorporate fermented tobacco. See also the types of tobacco processing techniques described in PCT Application Publication No. WO2005 / 063060 (Atchley et al.) (incorporated herein by reference).

[0126] When used in the nanoemulsions or compositions disclosed herein, tobacco materials are generally used in a form that can be described as particulate (i.e., in the form of shredded, ground, granulated, or powdered). Tobacco plants or parts thereof can be separated into individual parts or pieces (e.g., leaves can be removed from the stem, and / or the stem and leaves can be removed from the stalk). The harvested plants or individual parts or pieces can be further divided into parts or pieces (e.g., leaves can be shredded, cut, ground, micronized, granulated, or pulverized into pieces or parts that may be characterized as fill-type pieces, granules, particulates, or fine powders).

[0127] The method by which the tobacco material is provided in a finely divided or powder type form can be varied. Preferably, the plant parts or pieces are ground, milled or micronized into a granular form using devices and techniques such as grinding, milling, etc. Most preferably, the plant material is in a relatively dry form during grinding or micronization using devices such as hammer mills, cutter heads, air control mills, etc. For example, tobacco parts or pieces may be ground or micronized if the moisture content is less than about 15% by weight or less than about 5% by weight. The plant or its parts may be subjected to an external force or pressure (e.g., by being pressed or subjected to a rolling process). When carrying out such processing conditions, the plant or its parts may have a moisture content approximating its natural moisture content (e.g., its moisture content immediately after harvesting), a moisture content achieved by adding moisture to the plant or its parts, or a moisture content resulting from drying the plant or its parts. For example, the powder, micronized, ground or milled pieces of the plant, or its parts can have a moisture content of less than about 25% by weight, often less than about 20% by weight, and frequently less than about 15% by weight. Most preferably, the tobacco material is used in the form of parts or pieces having an average particle size between 1.4 mm and 250 microns. In some examples, the tobacco particles may be sized to pass through a screen mesh to obtain the required particle size range. If desired, an air classification device may be used to ensure the recovery of the smaller sized tobacco particles of the desired size or size range. If desired, pieces of granular tobacco of different sizes may be mixed together.

[0128] To prepare oral products, it is common to subject harvested plants of Nicotiana species to a curing process. For inclusion in the products disclosed herein, the tobacco material incorporated into the composition is appropriately cured and / or aged tobacco material. Descriptions of various types of curing processes for various types of tobacco are described in Tobacco Production, Chemistry and Technology, Davis et al., (Eds.)(1999). Examples of techniques and conditions for curing flue-cured tobacco are described in Nestor et al., Beitrage Tabakforsch.Int., 20, 467-475(2003), and U.S. Patent No. 6,895,974 (Peele), which are incorporated herein by reference. Representative techniques and conditions for air-curing tobacco are described in U.S. Patent No. 7,650,892 (Groves et al.), Roton et al., Beitrage Tabakforsch.Int., 21, 305-320(2005) and Staaf et al., Beitrage Tabakforsch.Int., 21, 321-330(2005), which are incorporated herein by reference. Certain types of tobacco can be subjected to alternative types of curing processes such as fire-curing or sun-curing.

[0129] In certain embodiments, tobacco materials that can be used include iron-pipe dried or Virginia varieties (e.g., K326), Burley varieties, sun-dried (e.g., Indian Kurnool and Oriental tobacco including Katerini, Prelip, Komotini, Xanthi and Yambol tobacco), Maryland varieties, dark, dark-fired, dark air cured (e.g., Madole, Passanda, Cubano, Jatin and Bezuki tobacco), light air cured (e.g., North Wisconsin and Galpao tobacco), Indian air dried, Red Russian and Rustica tobacco, and various other rare or special tobaccos and various blends of any of the foregoing tobaccos.

[0130] The tobacco material may also have a so-called "blended" form. For example, the tobacco material may include a mixture of parts or pieces of iron-pipe dried, Burley varieties (e.g., Malawi Burley tobacco) and Oriental tobacco (e.g., tobacco composed of or derived from tobacco leaf pieces or a mixture of tobacco leaf pieces and tobacco stems). For example, a representative blend may incorporate, based on dry weight, about 30 to about 70 parts of Burley variety tobacco (e.g., leaf pieces or leaf pieces and stems), about 30 parts to about 70 parts of iron-pipe dried tobacco (e.g., stems, leaf pieces or leaf pieces and stems). Other example tobacco blends incorporate, based on dry weight, about 75 parts of iron-pipe dried tobacco, about 15 parts of Burley variety tobacco, and about 10 parts of Oriental tobacco; or about 65 parts of iron-pipe dried tobacco, about 25 parts of Burley variety tobacco, about 10 parts of Oriental tobacco; or about 65 parts of iron-pipe dried tobacco, about 10 parts of Burley variety tobacco, and about 25 parts of Oriental tobacco. Other example tobacco blends incorporate, based on dry weight, about 20 parts to about 30 parts of Oriental tobacco, and about 70 parts to about 80 parts of iron-pipe dried tobacco.

[0131] The tobacco material used in the present disclosure may be subjected to, for example, fermentation, decolorization, etc. If desired, the tobacco material may be, for example, irradiated, pasteurized, or subjected to a controlled heat treatment. Such treatment steps are detailed, for example, in U.S. Patent No. 8,061,362 (Mua et al.) and are incorporated herein by reference. In certain embodiments, the tobacco material can be treated with an additive that can inhibit the reaction of aspartic acid to form acrylamide when the water and the tobacco material are heated (for example, 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 functionality, oxidizing agents, oxidation catalysts, natural plant extracts (for example, rosemary extract), and additives selected from the group consisting of combinations thereof). For example, it is described in U.S. Patent Application Nos. 8,434,496, 8,944,072, and 8,991,403 (Chen et al.) (incorporated herein by reference). In certain embodiments, this type of treatment is useful when the original tobacco material is subjected to heat in the aforementioned steps.

[0132] In various embodiments, the tobacco material can be processed to extract soluble components of the tobacco material therefrom. As used herein, "tobacco material" refers to the isolated components of the tobacco material that are extracted from solid tobacco pulp by a solvent that contacts the tobacco material in the extraction process. Various extraction techniques of the tobacco material can be used to provide tobacco extracts and tobacco solid materials. See, for example, the extraction process described in U.S. Patent Application Publication No. 2011 / 0247640 (Beeson et al.), which is incorporated herein by reference.Other example techniques for extracting tobacco components are described in U.S. Patent Nos. 4,144,895 (Fiore), 4,150,677 (Osborne, Jr. et al.), 4,267,847 (Reid), 4,289,147 (Wildman et al.), 4,351,346 (Brummer et al.), 4,359,059 (Brummer et al.), 4,506,682 (Muller), 4,589,428 (Keritsis), 4,605,016 (Soga et al.), 4,716,911 (Poulose et al.), 4,727,889 (Niven, Jr. et al.), 4,887,618 (Bernasek et al.), 4,941,484 (Clapp et al.), 4,967,771 (Fagg et al.), 4,986,286 (Roberts et al.), 5,005,593 (Fagg et al.), 5,018,540 (Grubbs et al.), 5,060,669 (White et al.), 5,065,775 (Fagg), 5,074,319 (White et al.), 5,099,862 (White et al.), 5,121,757 (White et al.), 5,131,414 (Fagg), 5,131,415 (Munoz et al.), 5,148,819 (Fagg), 5,197,494 (Kramer), 5,230,354 (Smith et al.), 5,234,008 (Fagg), 5,243,999 (Smith), 5,301,694 (Raymond et al.), 5,318,050 (Gonzalez-Parra et al.), 5,343,879 (Teague), 5,360,022 (Newton), 5,435,325 (Clapp et al.), 5,445,169 (Brinkley et al.), 6,131,584 (Lauterbach), 6,298,859 (Kierulff et al.), 6,772,767 (Mua et al.), and 7,337,782 (Thompson), all of which are incorporated herein by reference.

[0133] In some embodiments, the type of tobacco material is selected such that the tobacco material is visually somewhat brighter in color (e.g., white or decolorized) than other tobacco materials at first. In certain embodiments, the tobacco pulp can be whitened according to any means known in the art.

[0134] The general inclusion range of the tobacco material can vary depending on the nature and type of the tobacco material and the intended effect on the nanoemulsion, composition, or final product incorporating the composition, but exemplary ranges are up to about 30 wt% (or up to about 20 wt% or up to about 10 wt% or about up to 5 wt%) (e.g., about 0.1 to about 15 wt%) based on the total weight of the composition. In some embodiments, the products of the present disclosure (including nanoemulsions, nanoemulsion-containing compositions, and compositions incorporating the composition) can be characterized by containing no or substantially no tobacco material (other than purified nicotine as a possible active ingredient). In some embodiments, such products are described as having no intentionally added tobacco material (other than purified nicotine as a possible active ingredient). For example, certain embodiments may be characterized by having less than 1 wt% or less than 0.5 wt% or less than 0.1 wt% of tobacco material or 0 wt% of tobacco material based on the total weight of the nanoemulsion, nanoemulsion-containing composition, or product incorporating the nanoemulsion or composition.

[0135] Other additives Other additives may be included in the disclosed nanoemulsion or composition comprising a nanoemulsion. For example, the nanoemulsion or composition comprising a nanoemulsion can be processed, blended, formulated, combined, and / or mixed with other materials or components. The additives may be artificial or may be derived from plants or biological sources. Examples of further types of additives include thickeners or gelling agents (such as fish gelatin), preservatives (such as potassium sorbate, etc.), disintegration aids, zinc or magnesium salts selected to have greater water solubility and be relatively water soluble in the composition (such as magnesium gluconate or zinc gluconate), or zinc or magnesium salts selected to have reduced water solubility and be relatively insoluble in the composition (such as magnesium oxide or zinc oxide) or combinations thereof. For example, reference is made to U.S. Patent No. 9,237,769 (Mua et al.), U.S. Patent No. 7,861,728 (Holton, Jr. et al.), U.S. Patent Application Publication No. 2010 / 0291245 (Gao et al.), and U.S. Patent Application Publication No. 2007 / 0062549 (Holton, Jr. et al.), which are hereby incorporated by reference in their entirety. The general scope of inclusion of such additional additives can vary depending on the nature and function of the additive and the intended effect on the final composition, but an exemplary range is up to about 10 wt% (such as about 0.1 to about 5 wt%) based on the total weight of the nanoemulsion or composition comprising the nanoemulsion.

[0136] The foregoing additives can be used together (e.g., as an additive formulation) or separately (e.g., individual additive components can be added at different stages involved in the preparation of the final product). Further, additives of the foregoing types may be encapsulated so as to be provided in the final product or composition. Exemplary encapsulated additives are described, for example, in WO2010 / 132444 (Atchley), which is hereby incorporated by reference.

[0137] Preparation of the Nanoemulsion The nanoemulsions disclosed herein can be prepared by mechanical processes that use shear forces to break large emulsion droplets into smaller droplets, such as high-pressure homogenization (including microfluidization), high-amplitude ultrasonic processing, and ultrasonic-assisted emulsification. Generally, the nanoemulsions of the present disclosure can be prepared by preparing an aqueous phase containing an emulsifier (e.g., an amphiphilic molecule or surfactant) disclosed herein, homogenizing this solution with a homogenizer or mixer for a certain period of time, and preparing an oil phase containing oil as described above herein. One or more hydrophobic active ingredients, fragrances, or combinations thereof can be added to the aqueous phase and / or the oil phase, if desired, and subsequently mixed with a suitable mixing device. The aqueous phase and the oil phase can be combined and homogenized, for example, with a probe sonicator (Sonics and Materials, Inc., USA), a high-pressure homogenizer (e.g., manufactured by Gauline or Avestine), or a microfluidization device to obtain the desired nanoemulsion. The number of passes through the high-pressure homogenizer / microfluidization device can be varied depending on the desired particle size of the nanoemulsion. For example, various methods for producing nanoemulsions containing nanoparticles in a specific size range using sonication or homogenization are known in the art. One such method is described in U.S. Patent No. 4,737,323, which is incorporated herein by reference.

[0138] Properties of Nanoemulsions The nanoemulsions disclosed herein generally contain nanoscale particles having an average size of about 10 to about 1,000 nm, such as about 10 to about 200 nm, about 20 to about 100 nm, or about 40 to about 100 nm. In some embodiments, the average particle size is about 100, about 90, about 80, about 70, about 60, about 50, or about 40 nm. In some embodiments, the average particle size is about 40 to about 60 nm. In some embodiments, the average particle size is about 40 to about 60 nm and the nanoemulsion is transparent.

[0139] The size of the nanoparticles can be determined by the quasi-elastic light scattering method (QELS) described in Bloomfield, Ann.Rev.Biophys.Bioeng., 10:421-450(1981) (incorporated herein by reference). The average particle size can also be measured by correlation spectroscopy or transmission electron microscopy (TEM) that analyzes the fluctuations in the scattering of light due to Brownian motion.

[0140] The nanoemulsions disclosed herein can be characterized by reference to the polydispersity index. Polydispersity indicates the homogeneity of the droplet size of the nanoemulsion. The larger the value of the polydispersity, the lower the homogeneity of the droplet size. Polydispersity can be defined as the ratio of the standard deviation to the average droplet size. This can be measured by spectrophotometry. In some embodiments, it may be advantageous to provide nanoemulsions with a low polydispersity index, for example less than about 0.5. In some embodiments, the nanoemulsion has a polydispersity index of less than about 0.3.

[0141] The nanoemulsions disclosed herein can be characterized by reference to the zeta potential. The zeta potential is a measure of the charge on the surface of the droplets in the nanoemulsion. In some embodiments, the zeta potential of the nanoparticles is from about -40 mV to about 40 mV.

[0142] configured for oral use The nanoemulsions, compositions, and products disclosed herein are configured for oral use. As used herein, the term "configured for oral use" means that during use of the product, the nanoemulsion, composition, or one or more of the components of the product (e.g., flavor and / or active ingredient) are provided in a form that passes through the user's mouth by the saliva in the user's mouth. In certain embodiments, the nanoemulsion, composition, or product is adapted to deliver components to the user by the user's oral cavity, digestive system, or both mucosae, and in some examples, the components are active ingredients that can be absorbed by the oral mucosa or, when the product is used, by the digestive tract.

[0143] The products configured for oral use described herein (incorporating the disclosed nanoemulsion or composition) may take various forms including gels, lozenges, gums, pastilles, powders, and pouches. The gel may be soft or hard. A particular product configured for oral use is in the form of a lozenge. As used herein, the term "lozenge" refers to a soluble oral product manufactured by solidifying a liquid or gel composition such that the final product is a somewhat hard solid gel. The rigidity of the gel is quite variable. Particular products of the present disclosure are in solid form. Particular products can exhibit, for example, one or more of the following characteristics: crunchy, gritty, chewy, syrupy, pasty, fluffy, smooth, and / or creamy. In certain embodiments, the desired texture characteristics can be selected from the group consisting of tackiness, adhesiveness, density, dryness, brittleness, granulosity, stickiness, hardness, heaviness, hygroscopicity, moisture release, mouthcoating, coarseness, slipperiness, smoothness, viscosity, wetness, and combinations thereof.

[0144] Products containing the nanoemulsions or compositions of the present disclosure may be soluble. As used herein, the terms "dissolve," "dissolving," and "capable of dissolving" refer to a composition having water-soluble components that interact with the moisture in the mouth and enter into solution, whereby the product is gradually consumed. In one aspect, a dissolvable product can persist in the user's mouth for a predetermined time until it completely dissolves. The dissolution rate can vary over a wide range from about 1 minute or less to about 60 minutes. For example, fast-release compositions generally dissolve and / or release the active substance in about 2 minutes or less, often about 1 minute or less (e.g., about 50 seconds or less, about 40 seconds or less, about 30 seconds or less, or 20 seconds or less). Dissolution can be caused by any means such as melting, mechanical disintegration (e.g., chewing), enzymatic or other chemical decomposition, or disintegration of the interaction between the components of the composition. In some embodiments, the product is meltable, as discussed, for example, in U.S. Patent Application Publication No. 2012 / 0037175 (Cantrell et al.). In other embodiments, the product does not dissolve while the product is present in the user's mouth.

[0145] In one embodiment, the product of the present disclosure is in the form of a composition containing the nanoemulsion described herein and is placed in a moisture-permeable container (water-permeable pouch). Such a composition in the form of a water-permeable pouch is generally used by placing one pouch containing the composition in the mouth of a human subject / user. Generally, the pouch is placed somewhere in the user's oral cavity, such as under the lip, in the same way that sniff tobacco is commonly used. The pouch is preferably not chewed or swallowed. Thereafter, upon exposure to saliva, some of the components of the composition in the pouch (e.g., flavorants and / or active ingredients) pass through, for example, the water-permeable pouch, giving the user flavor and satisfaction, and the user does not need to spit out any part of the composition. After about 10 minutes to about 60 minutes, usually about 15 minutes to about 45 minutes, after the start of use / enjoyment, a substantial amount of the composition is absorbed by the oral mucosa of the human subject, and the pouch may be removed from the human subject's mouth for disposal.

[0146] Accordingly, in certain embodiments, the nanoemulsion or composition and any other such components disclosed herein are adapted to a moisture permeable packet or pouch that acts as a container for the composition to provide a pouch product configured for oral use. Certain embodiments of the present disclosure are described with reference to FIG. 1 of the accompanying drawings, and these described embodiments relate to a snus-type product having an outer pouch and containing the composition described herein. As will be described in more detail below, such embodiments are merely exemplary, and the pouch products of the present disclosure may contain the composition in other forms. Such a packet or pouch, for example, the composition / structure of container pouch 102 in the embodiment shown in FIG. 1, can be varied. Referring to FIG. 1, a first embodiment of a pouch product 100 is shown. The pouch product 100 includes a moisture permeable container in the form of a pouch 102 and a material 104 containing the nanoemulsion or nanoemulsion-containing composition described herein.

[0147] Suitable packets, pouches or containers for use in the manufacture of smokeless tobacco products are available under the trade names CatchDry, Ettan, General, Granit, Goteborgs Rape, Grovsnus White, Metropol Kaktus, Mocca Anis, Mocca Mint, Mocca Wintergreen, Kicks, Probe, Prince, Skruf and TreAnkrare. The composition may be contained and packaged in a pouch in a manner that uses the types of ingredients used in the manufacture of normal snus-type products. The pouch provides a liquid permeable container of a type that may be considered to be similar in characteristics to the mesh-like type of material used for the construction of tea bags. The components of the composition diffuse easily through the pouch into the user's mouth.

[0148] Non-limiting examples of suitable types of pouches are described, for example, in U.S. Patent Nos. 5,167,244 (Kjerstad) and 8,931,493 (Sebastian et al.) and U.S. Patent Application Publication Nos. 2016 / 0000140 (Sebastian et al.), 2016 / 0073689 (Sebastian et al.), 2016 / 0157515 (Chapman et al.), and 2016 / 0192703 (Sebastian et al.), each of which is incorporated herein by reference. The pouches can be provided as individual pouches, or multiple pouches (e.g., 2, 4, 5, 10, 12, 15, 20, 25, or 30 pouches) can be connected or linked together (e.g., end-to-end) such that a single pouch or individual portion can be easily removed from an integral chain or matrix of pouches for use.

[0149] Exemplary pouches may be made from materials and in such a manner that the pouches undergo controlled dispersion or dissolution during use by a user. Such pouch materials may have forms such as a mesh, screen, perforated paper, permeable cloth, etc. For example, a pouch material made from a mesh-like form of rice paper or perforated rice paper may be dissolved in a user's mouth. As a result, the pouch and the composition can each be completely dispersed in the user's mouth during normal use conditions, and thus both the pouch and the composition can be digested by the user. Other examples of pouch materials may be made using water-dispersible film-forming materials (e.g., binders such as alginates, carboxymethylcellulose, xanthan gum, pullulan, etc.) and materials such as ground cellulose (e.g., fine particle size wood pulp) in combination. Preferred pouch materials are water-dispersible or water-soluble, but are designed and manufactured such that a significant amount of the composition contents pass through the pouch material before the pouch loses its physical integrity under normal use conditions. If desired, flavor components, disintegration aids, and other desired components may be incorporated into or applied to the pouch material.

[0150] The amount per product unit, e.g., the amount of nanoemulsion or composition contained in a pouch, may vary. In some embodiments, the weight of the nanoemulsion or composition in each pouch is at least about 50 mg, e.g., about 50 mg to about 2 g, about 100 mg to about 1.5 g, or about 200 to about 700 mg. In some smaller embodiments, the weight of the nanoemulsion or composition in each pouch may be about 100 to about 300 mg. For larger embodiments, the weight of the material in each pouch may be about 300 mg to about 700 mg. If desired, other components may be included in each pouch. For example, at least one flavored piece, a piece or sheet of a flavored water-dispersible or water-soluble material (e.g., an edible film-type material for bad breath odor elimination) may be arranged with or without at least one capsule. Such pieces or sheets may be folded or rolled up for easy incorporation into the pouch. See, for example, the types of materials and techniques described in U.S. Patent Nos. 6,887,307 (Scott et al.) and 6,923,981 (Leung et al.) and The EFSA Journal (2004) 85, 1-32 (incorporated herein by reference).

[0151] In certain embodiments, one or more of the active ingredients described herein are included in the composition in the pouch product, and one or more additional active ingredients are placed in or on the outer surface of the product (e.g., on or in the pouch material disclosed herein). In some embodiments, the separate locations of the active ingredients may allow for different release characteristics (e.g., one active ingredient may be used rapidly for the mouth and / or digestive system, and another active ingredient may be released more slowly with product use).

[0152] The pouch products described herein can be packaged in any suitable inner packaging material and / or outer container. Also, for example, U.S. Patent Nos. 7,014,039 (Henson et al.), 7,537,110 (Kutsch et al.), 7,584,843 (Kutsch et al.), 8,397,945 (Gelardi et al.), D592,956 (Thiellier), D594,154 (Patel et al.), and D625,178 (Bailey et al.), U.S. Patent Publications 2008 / 0173317 (Robinson et al.), 2009 / 0014343 (Clark et al.), 2009 / 0014450 (Bjorkholm), 2009 / 0250360 (Bellamah et al.), 2009 / 0266837 (Gelardi et al.), 2009 / 0223989 (Gelardi), 2009 / 0230003 (Thiellier), 2010 / 0084424 (Gelardi), 2010 / 0133140 (Bailey et al.), 2010 / 0264157 (Bailey et al.), and 2011 / 0168712 (Bailey et al.), which are incorporated herein by reference, various types of containers for smokeless type products are also referred to.

[0153] Many modifications and other embodiments of the present invention will come to the mind of those skilled in the art to which the present invention pertains and have the benefit of the teachings presented in the foregoing description. Accordingly, it is to be understood that the present invention is not limited to the specific embodiments disclosed and that these modifications and other embodiments are intended to be included within the scope of the appended claims. Specific terms are used herein but are used in a general and descriptive sense only and not for purposes of limitation.

Claims

1. A pouch product configured for oral use, comprising a filler and a nanoemulsion dispersed or disposed in the filler, wherein the nanoemulsion comprises oil, water, 0.01 wt% to 15 wt% of an emulsifier, which is an emulsifier selected from surfactants, phospholipids, amphiphilic polysaccharides, amphiphilic proteins, or combinations thereof, and an active ingredient selected from the group consisting of plant materials, stimulants, amino acids, vitamins, antioxidants, nicotine components, cannabinoids, cannabis analogs, terpenes, dietary supplements, drugs, and combinations thereof .

2. The pouch product according to claim 1, wherein the oil comprises long-chain fatty acids, monoacylglycerols, diacylglycerols, triacylglycerols, or combinations thereof, and the acyl group is a long-chain fatty acid.

3. The pouch product according to claim 1, wherein the oil comprises mineral oil, castor oil, corn oil, coconut oil, sesame oil, linseed oil, olive oil, peanut oil, soybean oil, safflower oil, flaxseed oil, sunflower oil, olive oil, or combinations thereof.

4. The pouch product according to any one of claims 1 to 3, wherein the active ingredient is lipophilic.

5. The pouch product according to any one of claims 1 to 4, wherein the active ingredient is a generally oxidizable molecule.

6. The pouch product according to any one of claims 1 to 5, wherein the emulsifier is an ionic surfactant or a non-ionic surfactant.

7. The pouch product according to any one of claims 1 to 6, wherein the emulsifier comprises Tween 20, Tween 80, Span 20, Span 40, Span 60, Span 80, lecithin, hydrocolloid gum, modified starch, or combinations thereof.

8. The pouch product according to any one of claims 1 to 7, further comprising a stabilizer selected from the group consisting of polysaccharides and polyols.

9. The pouch product according to any one of claims 1 to 8, comprising nanoparticles having a size of 20 to 200 nm.

10. The pouch product according to claim 9, wherein the zeta potential of the nanoparticles is -40 mV to 40 mV.

11. The pouch product according to any one of claims 1 to 10, wherein the nanoemulsion comprises particles having a polydispersity index of less than 0.

3.

12. The pouch product according to claim 1, wherein the pouch product substantially does not contain nicotine.

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