Nanoemulsions containing cannabinoids and / or cannabinoid analogues

Abstract

The present disclosure provides nanoemulsions comprising one or more active ingredients (e.g., one or more cannabinoids and / or cannabinoid analogs) formulated for use as tinctures or shots. Such nanoemulsions, tinctures and shots can exhibit high physical stability, e.g., no observable phase separation over periods of 6 months or more, or 12 months or more.

Description

[Technical field]

[0001] The present disclosure relates to emulsions containing one or more active ingredients and products containing such emulsions. [Background technology]

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

[0003] Oral product configurations combining tobacco materials with various binders and fillers have been proposed more recently, with exemplary product formats including lozenges, pastilles, gels, extruded forms, etc. See, for example, U.S. Patent Application Publication No. 2008 / 0196730 to Engstrom et al.; U.S. Patent Application Publication No. 2008 / 0305216 to Crawford et al.; U.S. Patent Application Publication No. 2009 / 0293889 to Kumar et al.; U.S. Patent Application Publication No. 2010 / 0291245 to Gao et al.; U.S. Patent Application Publication No. 2011 / 0139164 to Mua et al.; U.S. Patent Application Publication No. 2012 / 0037175 to Cantrell et al.; U.S. Patent Application Publication No. 2012 / 0055494 to Hunt et al.; U.S. Patent Application Publication No. 2012 / 0138073 to Cantrell et al.; U.S. Patent Application Publication No. 2012 / 0138073 to Cantrell et al. See the types of products described in U.S. Patent Application Publication No. 2012 / 0138074; U.S. Patent Application Publication No. 2013 / 0074855 to Holton, Jr.; U.S. Patent Application Publication No. 2013 / 0074856 to Holton, Jr.; U.S. Patent Application Publication No. 2013 / 0152953 to Mua et al.; U.S. Patent Application Publication No. 2013 / 0274296 to Jackson et al.; U.S. Patent Application Publication No. 2015 / 0068545 to Moldoveanu et al.; U.S. Patent Application Publication No. 2015 / 0101627 to Marshall et al.; and U.S. Patent Application Publication No. 2015 / 0230515 to Lampe et al., each of which is incorporated herein by reference. Tobacco-free oral products of a similar format have also been proposed. [Prior art documents] [Patent documents]

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

[0005] It is desirable to provide products configured for oral use that can deliver the active ingredient to the consumer in alternative forms. [Means for solving the problem]

[0006] (Brief summary) The present disclosure generally relates to emulsions containing one or more active ingredients, and products containing such emulsions. For example, in some embodiments, such liquids are emulsions, such as nanoemulsions. Nanoemulsions can contain one or more active ingredients in concentrated form (e.g., in the form of a "tincture") and / or can be diluted to provide one or more active ingredients in diluted form (e.g., in the form of a "shot"). Advantageously, the disclosed liquids exhibit high stability, as assessed, for example, via physical observation.

[0007] The present disclosure includes, but is not limited to, the following embodiments: Embodiment 1: A nanoemulsion comprising a cannabinoid and / or cannabimimetic, a first oil, a second oil, and water, wherein the cannabinoid or cannabinoid analog is present in an amount of about 1% by weight or greater.

[0008] Embodiment 2: A nanoemulsion of embodiment 1, wherein the cannabinoid or cannabinoid analog is present in an amount of about 2% by weight or greater.

[0009] Embodiment 3: A nanoemulsion of embodiment 1, wherein the cannabinoid or cannabinoid analog is present in an amount of about 1% to about 4% by weight.

[0010] Embodiment 4: A nanoemulsion of embodiment 1, wherein the cannabinoid or cannabinoid analog is present in an amount of about 2% to about 3% by weight.

[0011] Embodiment 5: A nanoemulsion according to any one of embodiments 1 to 4, wherein the cannabinoid or cannabinoid analogue is selected from the group consisting of cannabigerol, cannabichromene, cannabidiol, tetrahydrocannabinol, cannabinol, cannabinodiol and combinations thereof.

[0012] Embodiment 6: A nanoemulsion according to any one of embodiments 1 to 4, wherein the cannabinoid or cannabinoid analogue is selected from the group consisting of cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabiditriol (CBO), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarinic acid (THCV A), and combinations thereof.

[0013] Embodiment 7: A nanoemulsion according to any of embodiments 1 to 4, wherein the cannabinoid or cannabinoid analog comprises cannabidiol (CBD).

[0014] Embodiment 8: A nanoemulsion according to any of embodiments 1 to 4, wherein the cannabinoid or cannabinoid analogue is selected from the group consisting of yangonin, alpha-amyrin or beta-amyrin (also classified as terpenes), cyanidin, curcumin (turmeric), catechin, quercetin, salvinorin A, N-acylethanolamines, N-alkylamide lipids, and combinations thereof.

[0015] Embodiment 9: A nanoemulsion described in any of embodiments 1 to 8, wherein the first oil comprises sunflower oil.

[0016] Embodiment 10: A nanoemulsion described in any of embodiments 1 to 9, wherein the second oil comprises lecithin.

[0017] Embodiment 11: A nanoemulsion described in any of embodiments 1 to 10, wherein the second oil is canola lecithin.

[0018] Embodiment 12: A nanoemulsion described in any of embodiments 1 to 11, wherein the weight ratio of the second oil to the first oil is about 1.5 or more.

[0019] Embodiment 13: A nanoemulsion described in any of embodiments 1 to 12, wherein the weight ratio of the second oil to the first oil is from about 1.5 to about 3.

[0020] Embodiment 14: A nanoemulsion according to any one of embodiments 1 to 13, further comprising a surfactant.

[0021] Embodiment 15: A nanoemulsion according to embodiment 14, wherein the surfactant is polyoxyethylene stearate.

[0022] Embodiment 16: A nanoemulsion described in any one of embodiments 1 to 15, further comprising one or more natural or artificial sweeteners.

[0023] Embodiment 17: A nanoemulsion according to embodiment 16, wherein the natural or artificial sweetener is selected from the group consisting of saccharin, acesulfame K, aspartame, sucralose, isomalt, lactose, mannitol, sorbitol, xylitol, sucrose, stevia, and combinations thereof.

[0024] Embodiment 18: A nanoemulsion described in embodiment 17, wherein the natural or artificial sweetener comprises stevia.

[0025] Embodiment 19: A nanoemulsion according to any one of embodiments 1 to 18, further comprising a bitterness suppressant.

[0026] Embodiment 20: A nanoemulsion described in embodiment 19, wherein the bitterness suppressant is glycyrrhizinic acid or a salt thereof.

[0027] Embodiment 21: A nanoemulsion according to any one of embodiments 1 to 20, further comprising an antioxidant.

[0028] Embodiment 22: A nanoemulsion according to embodiment 21, wherein the antioxidant is selected from the group consisting of citric acid, vitamin E, tocopherol, epicatechol, epigallocatechol, epigallocatechol gallate, erythorbic acid, sodium erythorbate, ascorbyl palmitate, ascorbyl stearate, sodium ascorbate, ascorbic acid, 4-hexylresorcinol, theaflavin, theaflavin monogallate A or B, theaflavin digallate, phenolic acids, glycosides, quercitrin, isoquercitrin, hyperosides, polyphenols, catechol, resveratrol, oleuropein, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tertiary butylhydroquinone (TBHQ), and combinations thereof.

[0029] Embodiment 23: A nanoemulsion according to any one of embodiments 1 to 22, further comprising a wetting agent.

[0030] Embodiment 24: A nanoemulsion according to embodiment 23, wherein the wetting agent is a polyol.

[0031] Embodiment 25: A nanoemulsion according to embodiment 23, wherein the humectant comprises glycerin, propylene glycol, 1,3-propanediol, dipropylene glycol, sorbitol, xylitol, mannitol, or a combination thereof.

[0032] Embodiment 26: A nanoemulsion according to any of embodiments 1 to 25, which is substantially free of monoalcohol (including but not limited to, for example, ethanol).

[0033] Embodiment 27: A nanoemulsion according to any of embodiments 1 to 26, comprising a dispersed phase in water, the dispersed phase having an average droplet size of about 100 nm or less.

[0034] Embodiment 28: A nanoemulsion according to any one of embodiments 1 to 27, exhibiting physical stability for at least 6 months.

[0035] Embodiment 29: A nanoemulsion described in any one of embodiments 1 to 27, exhibiting physical stability for 12 months or more.

[0036] Embodiment 30: An oral product in the form of a tincture, consisting essentially of the nanoemulsion of any of embodiments 1 to 29.

[0037] Embodiment 31: An oral product in the form of a shot comprising a nanoemulsion according to any one of embodiments 1 to 29, diluted in water.

[0038] Embodiment 32: The oral product of embodiment 31, further comprising at least one buffering agent, at least one preservative, at least one antioxidant, or any combination thereof (e.g., comprising at least one buffering agent, at least one preservative, and at least one antioxidant).

[0039] Embodiment 33: The oral product of any of embodiments 31-32, wherein the shot exhibits physical stability for 6 months or more.

[0040] Embodiment 34: The oral product of any of embodiments 31-33, wherein the shot exhibits physical stability for 12 months or more.

[0041] These and other features, aspects and advantages of the present disclosure will become apparent upon reading the following detailed description in conjunction with the accompanying drawings. Briefly described below. The present invention includes any combination of two, three, four or more of the above-described embodiments, including any combination of two, three, four or more features or elements described in this disclosure, regardless of whether such features or elements are explicitly combined with the description of a specific embodiment herein. Since this disclosure is intended to be read in a unified manner, it should be considered that any separate features or elements of the disclosed invention are intended to be combined in any of its various aspects and embodiments, unless the context clearly indicates otherwise. Other aspects and advantages of the present disclosure will become apparent below.

[0042] Having described aspects of the disclosure in general terms above, reference is now made to the accompanying drawings, which are not necessarily drawn to scale and which are illustrative and should not be construed as limiting the disclosure. [Brief description of the drawings]

[0043] [Figure 1] 1 is a dynamic light scattering plot for an example nanoemulsion provided by one embodiment of the present disclosure. [Diagram 2] 1 is a dynamic light scattering plot for an example of an aged nanoemulsion provided by one embodiment of the present disclosure. [Diagram 3] 1 is a dynamic light scattering plot for an example of a dilute nanoemulsion (in the form of a drinkable shot) provided by one embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0044] The present disclosure will now be described more fully hereinafter with reference to exemplary embodiments thereof. These exemplary embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art. Indeed, the present disclosure may be embodied in many different forms, and should not be construed as limited to the embodiments set forth herein, but rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. As used in this specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. References to "percentage by dry weight" or "on a dry weight basis" refer to weight based on dry ingredients (i.e., all ingredients except water). References to percentages are intended to mean percent by weight, unless otherwise indicated.

[0045] As described herein below, exemplary embodiments of the present disclosure relate to liquids that contain one or more active ingredients. The liquids can be used directly (e.g., in the form of a tincture for delivery of the active agent) or can be further processed (e.g., by diluting to form a shot for delivery of the active agent or by further processing to incorporate the liquid into another type of product (e.g., in a food, beverage, liquid-filled oral capsule, etc.).

[0046] In some embodiments, such liquids are suitable / configured for oral use / consumption, and can be further formulated or processed, for example, to be placed directly in the subject's mouth or to be included in a product that is inserted into the subject's mouth. In certain embodiments, the liquid (or a product containing such liquid) is adapted to deliver an ingredient to the subject through the mucous membranes in the subject's mouth and / or through the subject's digestive system, and in some cases, the ingredient is an active ingredient that can be absorbed through the mucous membranes in the oral cavity and / or the digestive system when the liquid (or a product containing the liquid) is used.

[0047] The liquids provided herein are generally in the form of emulsions, particularly in the form of nanoemulsions. The terms "emulsion" and "nanoemulsion" have their usual meaning in the chemical and pharmaceutical arts. For example, an emulsion can be described as a dispersion of droplets of one liquid (dispersed phase) suspended in a second liquid (continuous phase), the two liquids usually not miscible with each other. The droplets are generally spherical. Emulsions can generally be oil-in-water emulsions (dispersed phase includes oil and continuous phase includes water) and water-in-oil emulsions (dispersed phase includes water and continuous phase includes oil). The emulsions disclosed herein are typically oil-in-water emulsions.

[0048] Nanoemulsions are emulsions with droplet sizes in the range of about 20 nm to about 500 nm (often about 100 nm to about 500 nm, e.g., about 100 nm to about 200 nm). In various embodiments, the nanoemulsions provided herein exhibit small droplet sizes, including, for example, Z-average droplet sizes of less than about 100 nm (e.g., about 50 nm to about 100 nm). Such small droplet sizes are advantageous, for example, in the delivery of active agents (described herein below). For example, the disclosed nanoemulsions allow active ingredients (especially highly lipophilic active ingredients) to be more easily absorbed due to the small droplet size of these nanoemulsions. Advantageously, in some embodiments, the droplet size (diameter) of the disclosed nanoemulsions is substantially homogeneous, i.e., has low polydispersity.

[0049] The nanoemulsions of the present disclosure comprise multiple components. Nanoemulsions generally comprise an active ingredient, a surfactant, a lipid component, and water. Typically, the active ingredient is contained within the dispersed phase. The dispersed phase droplets (also referred to herein as "micelles" or "particles") can maintain the solubility of the active ingredient in the aqueous environment of, for example, the stomach during digestion and can protect the active ingredient from enzymes in the stomach and intestine. Ultimately, these droplets are transported to the intestinal wall where they are absorbed; as mentioned above, the small droplet size provides the disclosed nanoemulsions with advantages in providing easy absorption of the active ingredient. Each of these components is described more fully herein below with non-limiting examples, and additional components that can be optionally incorporated into the disclosed nanoemulsions are similarly disclosed.

[0050] Active ingredient One component of the nanoemulsions and related products provided herein is an active agent (also referred to herein as an "active ingredient"). The present disclosure is particularly advantageous in the context of active ingredients that are hydrophobic and / or lipophilic. Such active ingredients are not easily provided in aqueous solutions, and therefore delivery of such active ingredients can be a challenge. The compositions and methods outlined herein allow for the delivery of such hydrophobic and / or lipophilic active ingredients via a liquid (i.e., nanoemulsion) form. It is recognized that within the general class of active ingredients, certain examples are hydrophilic and certain examples are hydrophobic, as well as certain examples are lipophilic and certain examples are hydrophobic. The principles provided herein are particularly applicable in the context of those examples that are substantially hydrophobic and / or those examples that are substantially lipophilic.

[0051] The active ingredient may be any known agent suitable for therapeutic, prophylactic or diagnostic use. These may include, for example, synthetic organic compounds, proteins and peptides, polysaccharides and other sugars, lipids, inorganic compounds and nucleic acid sequences with therapeutic, prophylactic or diagnostic activity. Examples of active ingredients include any ingredient known to affect one or more biological functions in the body, such as ingredients that provide pharmacological activity or other direct action in the diagnosis, cure, mitigation, treatment or prevention of disease, or affect the structure or any function of the human or other animal body (e.g., provide a stimulating effect in the central nervous system, have an energizing effect, an antipyretic or analgesic effect, or another useful effect in the body). Active ingredients include, but are not limited to, cannabinoids and cannabinoid analogs.

[0052] 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 in cells, also known as the endocannabinoid system, to modify the release of neurotransmitters in the brain.The 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 produced. Cannabinoids found in cannabis include, but are not limited to, cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabiditriol (CBO), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabivarinic acid (THCV A). In certain embodiments, the cannabinoid is selected from tetrahydrocannabinol (THC), the main psychoactive compound in cannabis, and cannabidiol (CBD), another major component of the plant, but lacking psychoactivity. All of the above compounds can be used in the form of isolates from plant material or can be derived synthetically.

[0053] In some embodiments, the cannabinoid is selected from the group consisting of cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN) and cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabidiol (CBO), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarinic acid (THCV A), and mixtures thereof. In some embodiments, the cannabinoid comprises at least tetrahydrocannabinol (THC). In some embodiments, the cannabinoid is tetrahydrocannabinol (THC). In some embodiments, the cannabinoid comprises at least cannabidiol (CBD). In some embodiments, the cannabinoid is cannabidiol (CBD). In some embodiments, the CBD is synthetic CBD.

[0054] Alternatively (or additionally), the active ingredient may be a cannabinoid analogue, which is a class of compounds derived from plants other than cannabis that have biological effects in the endocannabinoid system similar to cannabinoids. Examples include yangonin, alpha-amyrin or beta-amyrin (also classified as terpenes), cyanidin, curcumin (turmeric), catechin, quercetin, salvinorin A, N-acylethanolamines and N-alkylamide lipids. Such compounds may be used in the same amounts and ratios as described herein for cannabinoids.

[0055] The selection of the cannabinoid or cannabinoid analog and the particular percentage that may be present in the disclosed oral products will vary depending on the desired flavor, texture, and other attributes of the oral product.

[0056] In some embodiments, the cannabinoid is a synthetic cannabidiol. In some embodiments, the cannabinoid is used in the form of an isolate. In some embodiments, the cannabinoid (e.g., cannabidiol, CBD) is added to the nanoemulsion in the form of an isolate. An isolate is an extract from a plant, such as hemp, in which the active material of interest (in this case, a cannabinoid, such as CBD) is present in a high degree of purity, for example, greater than 95%, greater than 96%, greater than 97%, greater than 98%, or about 99% purity. In some embodiments, the cannabinoid is an isolate of CBD in a high degree of purity, and the amount of any other cannabinoid in the oral product does not exceed about 1% by weight of the oral product, for example, does not exceed about 0.5% by weight of the oral product, for example, does not exceed about 0.1% by weight of the oral product, for example, does not exceed about 0.01% by weight of the oral product.

[0057] The cannabinoid (e.g., CBD) or cannabinoid analog is typically concentrated within the disclosed nanoemulsions in an amount of at least about 0.5% by weight, e.g., at least about 1%, at least about 1.1%, at least about 1.2%, at least about 1.3%, at least about 1.4%, at least about 1.5%, at least about 1.6%, at least about 1.7%, at least about 1.8%, at least about 1.9%, at least about 2%, at least about 2.1%, at least about 2.2%, at least about 2.3%, at least about 2.4% or at least about 2.5%, with an upper limit of, e.g., about 5%, about 4%, about 3%, about 2.9%, about 2.8%, about 2.7% or about 2.6% by weight. In some embodiments, the compositions disclosed herein include a cannabinoid, such as CBD, in an amount of about 1% to about 3% by weight or about 2% to about 3% by weight based on the total weight of the nanoemulsion.

[0058] In some embodiments, the nanoemulsions may contain additional active ingredients in combination with (or instead of) the cannabinoid or cannabinoid analog. In some embodiments, two or more active ingredients may be incorporated into the same nanoemulsion. For example, in some embodiments, the nanoemulsions may contain one or more active ingredients in addition to the cannabinoid or cannabinoid analog. Such active ingredients may be, for example, APIs (active pharmaceutical ingredients), food additives, natural medicines, and naturally occurring substances that may have effects on humans. Examples of active ingredients include any ingredient known to affect one or more biological functions in the body, such as ingredients that provide pharmacological activity or other direct action in the diagnosis, cure, mitigation, treatment, or prevention of disease, or affect the structure or any function of the human body (e.g., provide a stimulating effect in the central nervous system, have an energizing effect, an antipyretic or analgesic effect, or another beneficial effect in the body). In some embodiments, the active ingredient may be of the type commonly referred to as a dietary supplement, nutraceutical, "phytochemical," or "functional food." These types of additives are sometimes defined in the art as including substances typically available from naturally occurring sources (e.g., botanical materials) that provide one or more beneficial biological effects (e.g., health promotion, disease prevention, or other medicinal properties), but are not classified or regulated as drugs.

[0059] Non-limiting examples of active ingredients include those that fall into the categories of botanical ingredients, stimulants, amino acids, nicotine ingredients, and / or pharmaceutical ingredients, nutritional ingredients, and medicinal ingredients (e.g., vitamins such as A, B3, B6, B12, and C). Each of these categories is further described herein below. The particular choice of active ingredient can vary depending on the desired characteristics of a particular nanoemulsion.

[0060] In some embodiments, the nanoemulsions include a botanical ingredient as an active ingredient (e.g., in addition to cannabinoids and / or cannabamimetic). As used herein, the term "botanical ingredient" or "botanical" refers to any plant or fungal derived material, including plant material in its natural form and plant material derived from natural plant material, such as an extract or isolate derived from the plant material, or treated plant material (e.g., plant material that has been heat treated, fermented, bleached, or otherwise processed that may alter the physical and / or chemical properties of the material). For purposes of this disclosure, "botanical" includes, but is not limited to, "herbal material," which refers to seed-bearing plants (e.g., teas or tisanes) that do not develop persistent woody tissue and are often valued for their medicinal or sensory qualities. Reference to botanical material as "non-tobacco" is intended to exclude tobacco material (i.e., does not include any Nicotiana species). In some embodiments, the nanoemulsions disclosed herein can be characterized as being free of any tobacco material (e.g., any embodiment disclosed herein can be completely or substantially free of any tobacco material). By "substantially free," it is meant that no tobacco material has been intentionally added. For example, certain embodiments can be characterized as having less than 0.001% tobacco by weight, or less than 0.0001% or even 0% tobacco by weight.

[0061] If present, botanicals are typically at a concentration of about 0.01% w / w to about 10% by weight based on the total weight of the composition, for example, about 0.01% w / w, about 0.05%, about 0.1% or about 0.5% to about 1%, about 2%, about 3%, about 4% or about 5% by weight.

[0062] Botanical materials useful in the present disclosure may include any of the compounds and sources described herein, including, but not limited to, mixtures thereof. Certain botanical materials of this type are sometimes referred to as dietary supplements, nutraceuticals, "phytochemicals" or "functional foods." Certain botanicals, as plant materials or extracts thereof, find use in traditional herbal medicines and are further described herein.Non-limiting examples of botanicals or botanically derived materials include ashwagandha, Bacopa monniera, baobab, basil, Centella asiatica, bupleurum, chamomile, cherry blossom, chlorophyll, cinnamon, citrus, clove, cocoa, cordyceps, curcumin, damiana, Dorstenia arifolia, Dorstenia odorata, essential oils, eucalyptus, fennel, Galphimia glauca, ginger, Ginkgo biloba, carrots (e.g., Panax ginseng), green tea, Griffonia simplicifolia, and the like. simplicifolia, Guarana, Cannabis sativa, Hemp, Hops, Jasmine, Kaempferia parviflora (Thai ginseng), Kava, Lavender, Lemon balm, Lemongrass, Licorice, Lutein, Maca, Matcha, Nardostachys chinensis, Oil extract of Viola odorata, Peppermint, Quercetin, Resveratrol, Rhizoma gastrodiae, Rhodiola, Rooibos, Rose essential oil, Rosemary, Sceletium tortuosum tortuosum, Schisandra, skullcap, spearmint extract, pepper, terpenes, tisane, turmeric, Turnera aphrodisiaca, valerian, white mulberry and yerba mate.

[0063] In some embodiments, the nanoemulsion comprises lemon balm. Lemon balm (Melissa officinalis) is a mildly lemon-scented herb from the same family as mint (Lamiaceae). The herb is native to Europe, North Africa and Western Asia. Lemon balm teas and essential oils and extracts are used in traditional and alternative medicine. In some embodiments, the nanoemulsion comprises a lemon balm extract. In some embodiments, the lemon balm extract is present in an amount of about 0.1 to about 4% by weight based on the total weight of the composition.

[0064] In some embodiments, the nanoemulsion comprises ginseng. Ginseng is the root of a plant of the genus Panax, and ginseng is characterized by the presence of unique steroidal saponin phytochemicals (ginsenosides) and gintonin. Ginseng finds use 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). American ginseng and Korean ginseng vary in the types and amounts of various ginsenosides present. In some embodiments, the ginseng is American ginseng or Korean ginseng. In a specific embodiment, the active ingredient comprises Korean ginseng. In some embodiments, the ginseng is present in an amount of about 0.4 to about 0.6% by weight based on the total weight of the nanoemulsion.

[0065] In some embodiments, the nanoemulsion includes 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, e.g., improves focus, cognition, energy, mood, alertness, etc. Non-limiting examples of stimulants include caffeine, theacrine, theobromine, and theophylline. Theacrine (1,3,7,9-tetramethyluric acid) is a purine alkaloid that is structurally related to caffeine and has stimulating, analgesic, and anti-inflammatory effects. The stimulant may be natural, naturally derived, or completely synthetic. For example, certain botanical materials (guarana, tea, coffee, cocoa, etc.) may have a stimulant effect, e.g., due to the presence of caffeine or related alkaloids, and are therefore "natural" stimulants. "Naturally derived" means that the stimulant (e.g., caffeine, theacrine) is in a purified form outside of its natural (e.g., botanical) matrix. For example, caffeine can be obtained by extraction and purification from botanical sources (e.g., tea). "Fully synthetic" means that the stimulant is obtained by chemical synthesis. In some embodiments, the active ingredient comprises caffeine. In some embodiments, the caffeine is present in an encapsulated form. One example of encapsulated caffeine is Vitashure®, available from Balchem ​​Corp., 52 Sunrise Park Road, New Hampton, NY, 10958.

[0066] When present, the stimulant or combination of stimulants (e.g., caffeine, theacrine, and combinations thereof) is typically at a concentration of about 0.1% w / w to about 15% by weight based on the total weight of the composition, e.g., about 0.1% w / w, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, or about 0.9% to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, or about 15% by weight. In some embodiments, the composition comprises caffeine in an amount of about 1.5 to about 6% by weight based on the total weight of the nanoemulsion.

[0067] In some embodiments, the nanoemulsion includes an amino acid as an active ingredient. As used herein, the term "amino acid" refers to an organic compound containing an amine (-NH2) and a carboxyl (-COOH) or sulfonic acid (SO3H) functional group with a side chain (R group) that is specific to each amino acid. An amino acid can be proteinogenic or non-proteinogenic. "Proteogenic" means that the amino acid is one of the 12 naturally occurring amino acids found in proteins. Proteinogenic amino acids include alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. "Non-proteogenic" means that either amino acid is not naturally found in proteins or is not directly produced by intracellular 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. In some embodiments, the active ingredient includes theanine. In some embodiments, the active ingredient includes GABA. In some embodiments, the active ingredient includes a combination of theanine and GABA. In some embodiments, the active ingredient is a combination of theanine, GABA, and lemon balm. In some embodiments, the active ingredient includes a combination of theanine and tryptophan. In some embodiments, the active ingredient includes a combination of theanine and one or more B vitamins. In some embodiments, the nanoemulsion includes a combination of caffeine, theanine, and optionally ginseng. In some embodiments, the active ingredient includes taurine. In some embodiments, the active ingredient is a combination of caffeine and taurine.

[0068] Without being bound by any theory of operation, it is believed that certain amino acids, such as theanine, tryptophan, GABA, or taurine, can have beneficial effects on mood, anxiety levels, concentration, or cognitive performance, especially when combined with other active ingredients, such as caffeine or certain botanicals.

[0069] When present, the amino acid or combination of amino acids (e.g., theanine, taurine, GABA, tryptophan, and combinations thereof) are typically at a concentration of about 0.01% w / w to about 15% by weight based on the total weight of the nanoemulsion, e.g., about 0.1% w / w, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, or about 0.9% to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, or about 15% by weight. In one embodiment, the at least one active ingredient comprises tryptophan in an amount of about 0.03% to about 1% by weight or about 0.05% to about 0.5% by weight.

[0070] In some embodiments, the nanoemulsion comprises a vitamin or combination of vitamins as an active ingredient. As used herein, the term "vitamin" refers to an organic molecule (or set of related molecules) that is an essential micronutrient required for the normal functioning of metabolism in mammals. There are 13 vitamins required for human metabolism, which are vitamin A (as all-trans retinol, all-trans retinyl esters, and all-trans beta-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 (tocopherol and tocotrienol), and vitamin K (quinone). In some embodiments, the active ingredient comprises vitamin C. In some embodiments, the active ingredient is a combination of vitamin C, caffeine, and taurine. In some embodiments, the active ingredient includes one or more of vitamins B6 and B12. In some embodiments, the active ingredient includes theanine and one or more of vitamins B6 and B12. If present, a vitamin or combination of vitamins (e.g., vitamin B6, vitamin B12, vitamin E, vitamin C, or combinations thereof) is typically at a concentration of about 0.0001% to about 6% by weight based on the total weight of the composition, for example, about 0.0001, about 0.001, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, or about 0.1% w / w to about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, about 4%, about 5%, or about 6% by weight.

[0071] In some embodiments, the nanoemulsion comprises vitamin B6 in an amount of about 0.008% to about 0.06% by weight or about 0.01% to about 0.04% by weight. In some embodiments, the active ingredient comprises vitamin B12 in an amount of about 0.0001% to about 0.007% by weight or about 0.0005% to about 0.001% by weight. In some embodiments, the active ingredient comprises a combination of vitamin B6 and vitamin B12 in a total weight amount of about 0.008% to about 0.07% by weight. In some embodiments, the nanoemulsion comprises vitamin A. In some embodiments, the vitamin A is encapsulated.

[0072] In some embodiments, the nanoemulsion comprises a mineral as an active ingredient. As used herein, the term "mineral" refers to an inorganic molecule (or set of related molecules) that is an essential micronutrient required for the normal functioning of various systems in mammals. Non-limiting examples of minerals include iron, zinc, copper, selenium, chromium, cobalt, manganese, calcium, phosphorus, sulfur, magnesium, and the like. In some embodiments, the active ingredient comprises iron. Suitable sources of iron include, but are not limited to, iron salts, such as ferrous sulfate and ferrous gluconate. In some embodiments, the iron is encapsulated.

[0073] In certain embodiments, the nanoemulsion comprises a nicotine component as an active ingredient. By "nicotine component" is meant any form of natural or synthetic nicotine (e.g., free base or salt) suitable for providing oral absorption of at least a portion of the nicotine present. Typically, the nicotine component is selected from the group consisting of nicotine free base and nicotine salt. In some embodiments, the nicotine component is nicotine in its free base form, which can be readily absorbed, for example, in microcrystalline cellulose materials forming a microcrystalline cellulose-nicotine carrier complex. See, for example, the discussion of nicotine in the free base form in U.S. Patent Publication No. 2004 / 0191322 to Hansson, which is incorporated herein by reference.

[0074] In some embodiments, at least a portion of the nicotine component can be utilized in the form of a salt. The nicotine salt can be provided using the types of ingredients and techniques described in U.S. Patent No. 2,033,909 to Cox et al. and Perfetti, Beitrage Tabakforschung Int., 12:43-54 (1983), which are incorporated herein by reference. In addition, nicotine salts are available from sources such as Pfaltz and Bauer, Inc. and K&K Laboratories, Division of ICN Biochemicals, Inc. Typically, the nicotine component is selected from the group consisting of nicotine free base, nicotine salts, such as hydrochloride, dihydrochloride, monotartrate, bitartrate, sulfate, salicylate, and nicotine zinc chloride.

[0075] Typically, the nicotine component (calculated as the free base), when present, is at least about 0.001% by weight of the nanoemulsion, e.g., at a concentration ranging from about 0.001% to about 10%. In some embodiments, the nicotine component is present at a concentration of about 0.1% w / w to about 10% by weight, e.g., about 0.1% w / w, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, or about 0.9% to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% by weight, calculated as the free base based on the total weight of the nanoemulsion. In some embodiments, the nicotine component is present at a concentration of about 0.1% w / w to about 3% by weight, calculated as the free base based on the total weight of the composition, e.g., about 0.1% w / w to about 2.5%, about 0.1% to about 2.0%, about 0.1% to about 1.5%, or about 0.1% to about 1% by weight. In some embodiments, the nanoemulsions of the present disclosure can be characterized as being free of any nicotine component (e.g., any embodiment disclosed herein can be completely or substantially free of any nicotine component). By "substantially free" it is meant that nicotine has not been intentionally added beyond trace amounts that may be naturally present, for example, in botanical materials. For example, certain embodiments can be characterized as having less than 0.001% by weight nicotine, or less than 0.0001% by weight or even 0% by weight nicotine, calculated as the free base.

[0076] In some embodiments, the disclosed nanoemulsions may include one or more terpenes as active ingredients, many of which are associated with biological effects, such as sedative effects. Terpenes have the general formula (C5H8): nIt is understood that the terpenes have the formula: and include monoterpenes, sesquiterpenes, and diterpenes. Terpenes can be acyclic, monocyclic, or bicyclic in structure. Some terpenes, when used in combination with cannabinoids or cannabinoid analogs, produce an entourage effect. Examples include beta-caryophyllene, linalool, limonene, beta-citronellol, linalyl acetate, pinene (alpha or beta), geraniol, carvone, eucalyptol, menthone, iso-menthone, piperitone, myrcene, beta-bourbonene, and germacrene. These can be used alone or in combination.

[0077] In some embodiments, the terpene is a terpene derived from a phytocannabinoid-producing plant, such as a plant from a strain of the cannabis sativa species, such as hemp. Suitable terpenes in this regard include those terpenes that contain 10 carbon atoms, so-called "C10" terpenes, and those terpenes that contain 15 carbon atoms, so-called "C15" terpenes. In some embodiments, the active ingredient comprises two or more terpenes. For example, the active ingredient may comprise one, two, three, four, five, six, seven, eight, nine, ten, or more terpenes as defined herein. In some embodiments, the terpene is selected from pinene (alpha and beta), geraniol, linalool, limonene, carvone, eucalyptol, menthone, iso-menthone, piperitone, myrcene, beta-bourbonene, germacrene, and mixtures thereof.

[0078] In some embodiments, the nanoemulsions contain an active pharmaceutical ingredient (API) as an active ingredient. The API can be any known agent suitable for therapeutic, prophylactic or diagnostic use. These can include, for example, synthetic organic compounds, proteins and peptides, polysaccharides and other sugars, lipids, phospholipids, inorganic compounds (e.g., magnesium, selenium, zinc, nitrates), neurotransmitters or their precursors (e.g., serotonin, 5-hydroxytryptophan, oxytriptan, acetylcholine, dopamine, melatonin) and nucleic acid sequences that have therapeutic, prophylactic or diagnostic activity. Non-limiting examples of APIs include analgesics and antipyretics (e.g., acetylsalicylic acid, acetaminophen, 3-(4-isobutylphenyl)propanoic acid), phosphatidylserine, myo-inositol, docosahexaenoic acid (DHA, omega-3), arachidonic acid (AA, omega-6), S-adenosylmethionine (SAM), beta-hydroxy-beta-methylbutyrate (HMB), citicoline (cytidine-5'-diphosphate-choline), and cotinine. In some embodiments, the nanoemulsion includes citicoline. In some embodiments, the nanoemulsion includes a combination of citicoline, caffeine, theanine, and carrot. In some embodiments, the active ingredient includes sunflower lecithin. In some embodiments, the nanoemulsion includes a combination of sunflower lecithin, caffeine, theanine, and carrot.

[0079] The amount of API can vary. For example, if present, the API is typically at a concentration of about 0.001% w / w to about 10% by weight based on the total weight of the nanoemulsion, such as about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.1% w / w, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, or about 1% to about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% by weight.

[0080] In some embodiments, the nanoemulsion is substantially free of any API. By "substantially free of any API," it is meant that the nanoemulsion does not contain, and specifically excludes, the presence of any API as defined herein, such as any Food and Drug Administration (FDA) approved therapeutic agent intended to treat any medical condition. For example, certain embodiments can be characterized as having less than 0.001% by weight of API, or less than 0.0001% by weight, or even 0% by weight of API.

[0081] oil The nanoemulsions described herein comprise two or more oils. Advantageously, the active ingredient is at least partially soluble in at least one of the two or more oils. Advantageously, both the first oil and the second oil in various embodiments are food-grade oils, including, for example, fractionated oils. In certain embodiments, the first and / or second oils are selected to minimize allergic reactions.

[0082] The first oil may be, but is not limited to, a vegetable oil (e.g., acai oil, almond oil, amaranth oil, apricot kernel oil, apple seed oil, argan oil, avocado oil, babassu oil, beech nut oil, ben oil, bitter melon oil, black seed oil, black currant seed oil, borage seed oil, Borneo tallow nut oil, gourd oil, Brazil nut oil, buffalo gourd oil, butternut squash seed oil, Cape chestnut oil, canola oil, carob cashew oil, castor oil, cocoa butter, cocklebur oil, coconut oil, corn oil, coffea palm oil, coriander seed oil, cottonseed oil, date seed oil, dika oil, egusi seed oil, evening primrose oil, flaxseed oil, lin ... oil), grape seed oil, grapefruit seed oil, hazelnut oil, hemp oil, kapok seed oil, kenaf seed oil, lallemantia oil, lemon oil, linseed oil, macadamia oil, mafra oil, marula oil, meadowfoam seed oil, mongongo nut oil, mustard oil, niger seed oil, nutmeg butter, okra seed oil, olive oil, orange oil, palm oil, papaya seed oil, groundnut oil, pecan oil, perilla seed oil, perilla seed oil, oyster seed oil, pequi oil, pili nut oil, pine nut oil, pistachio oil, pomegranate seed oil, poppy seed oil, prakashi oil, prune kernel oil, pumpkin seed oil, quinoa oil, ramtil oil, rapeseed oil, rice bran oil, royle oil The oil may be selected from various types of oils, including oleaginous oils (e.g., oleaginous oil), sacha inchi oil, safflower oil, Mexican sable oil, seje oil, sesame oil, shea butter, soybean oil, sunflower oil, tarramilla oil, tea seed oil, thistle oil, tiger nut oil, tobacco seed oil, tomato seed oil, walnut oil, watermelon seed oil, wheat germ oil, and combinations thereof), animal oils (e.g., beef fat, buffalo fat, sheep fat, goat fat, porcine fat, lard, camel fat, tallow, liquid margarine, fish oil, fish liver oil, whale oil, seal oil, and combinations thereof), and mineral oils. The oil may be an omega-3 oil in some embodiments. In certain embodiments, the first oil is selected to provide good dissolution of the active ingredient. One example of a suitable first oil is sunflower oil.

[0083] The second oil can be selected similarly. In certain embodiments, the second oil comprises lecithin. Lecithin is generally a mixture of phospholipids (e.g., phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol) in oil, and can be obtained, for example, by degumming oil. The composition of lecithin can vary depending on the origin of the lecithin. Although lecithin is described herein as an example of a "second oil", it should be noted that the lecithin does not necessarily actually come from the corresponding oil. For example, canola lecithin is derived from the canola cultivar of rapeseed. Furthermore, in some embodiments, the second oil can function at least partially as a surfactant. Examples of lecithin include, but are not limited to, sunflower lecithin, soybean lecithin and canola lecithin.

[0084] Lecithin is available in native / crude and refined grades (typically heat treated, e.g., to remove proteins from the lecithin). In certain embodiments, the native / crude grades are more desirable than the refined grades. In some embodiments, the use of crude, unrefined lecithin (e.g., canola lecithin) surprisingly results in nanoemulsions with greater physical stability than those of nanoemulsions prepared using refined lecithin. Furthermore, it has been found that the use of canola lecithin (as opposed to, e.g., sunflower lecithin, soybean lecithin, and / or refined phosphatidylcholine) as the second oil surprisingly results in nanoemulsions with greater physical stability.

[0085] The first and second oils of the disclosed nanoemulsions can be provided in various amounts overall and in various ratios relative to each other. In some embodiments, the first and second oils together comprise about 10% by weight or more, about 15% by weight or more, about 16% by weight or more, about 17% by weight or more, about 18% by weight or more, about 19% by weight or more, or about 20% by weight or more, such as about 10% by weight to about 25% by weight or about 15% by weight to about 22% by weight. In some embodiments, the first and second oils are in approximately equal proportions to each other by weight. In other embodiments, the nanoemulsion comprises a higher weight percentage of the first oil or the second oil. For example, in some embodiments, the lecithin is provided in a higher weight percentage than the first oil (e.g., at least about 1.1 times the amount of the first oil, at least about 1.3 times the amount of the first oil, or at least about 1.5 times the amount of the first oil). Non-limiting examples of weight ratios of lecithin to the first oil include ratios of about 1.1:1 to about 2:1, e.g., about 1.2:1 to about 2:1, about 1.3:1 to about 2:1, about 1.4:1 to about 2:1, or about 1.5:1 to about 2:1.

[0086] Nanoemulsions are not limited to containing two oils, and in some embodiments, nanoemulsions can contain three or more or four or more oils. Such additional oils can be selected from the list provided above.

[0087] Surfactants Surfactants are generally included in the disclosed nanoemulsions and can function to help stabilize the nanoemulsions. Surfactants can be included in the continuous phase, the dispersed phase, or both phases of the nanoemulsion. Surfactant molecules typically contain both hydrophilic and hydrophobic regions and can therefore adsorb at the oil-water interface, lowering the interfacial tension and forming a protective layer around the dispersed phase droplets in the nanoemulsion. Surfactants can be ionic or non-ionic. In certain embodiments, the disclosed nanoemulsions include one or more anionic surfactants. Examples of anionic surfactants include, for example, sulfates, sulfonates, and carboxylates (with counterions such as ammonium, sodium, or potassium cations). Certain specific types of anionic surfactants are lauryl sulfate / laureto sulfate and alkyl sulfates, alkyl ether sulfates, alpha-olefin sulfonates. Surfactants can be further classified as hydrophilic or hydrophobic.

[0088] Examples of surfactants that can be used in the disclosed nanoemulsions include, but are not limited to, long chain triglycerides, such as C16-C18 triglycerides, linoleic acid, glyceryl monooleate, sodium lauryl sulfate (sodium dodecyl sulfate, SLS or SDS), docusate sodium, polyoxyethylene sorbitan fatty acid ester surfactants (including, for example, mono- and trilauryl, palmityl, stearyl and oleyl esters), such as those known as polysorbates and commercially available under the trade name TWEEN® (e.g., TWEEN® 20, TWEEN® 40, TWEEN® 65, TWEEN® 80 and TWEEN® 85); polyoxyethylene fatty acid esters, such as polyoxyethylene stearates, such as those commercially available under the trade name MYRJ™ (e.g., MYRJ™ 52); polyoxyethylene ethers, such as those commercially available under the trade name BRIJ™ (e.g., MYRJ™ 52); polyoxyethylene castor oil derivatives, such as those commercially available under the trade name SPAN® (e.g., SPAN® 20, SPAN® 40, SPAN® 60, SPAN® 65, SPAN® 80, and SPAN® 85); PEG glyceryl fatty acid esters, such as those commercially available under the trade name SPAN® (e.g., SPAN® 20, SPAN® 40, SPAN® 60, SPAN® 65, SPAN® 80, and SPAN® 85); PEG glyceryl fatty acid esters, such as PEG-8 glyceryl caprylate / caprate (commercially known as LABRASOL®).; polyoxyethylene-polyoxypropylene copolymers, such as those commercially available under the trade names PLURONIC® or POLOXAMER®; diethylene glycol-monoethyl ether (DGME), commercially known as TRANSCUTOL®; polyoxyethylene 15 hydroxystearate (Macrogol 15 hydroxystearate, Solutol HS15®); polyoxyethylene nonylphenol ether (NONOXYNOL®); PEG-4 glyceryl caprylate / caprate (Labrafac Hydro WL 1219); PEG-32 glyceryl laurate (Gelucire 44 / 14); PEG-6 glyceryl monooleate (Labrafil® M 1944 CS); PEG-6 glyceryl linoleate (Labrafil® M 2125 CS); monoglycerides and acetylated monoglycerides, such as glycerol monodicocoate (IMWITOR® 928) and glycerol monocaprylate (IMWITOR® 308); mono- and diacetylated monoglycerides; α-tocopherol; α-tocopheryl polyethylene glycol succinate (vitamin E TPGS); α-tocopherol palmitate and α-tocopherol acetate; propylene glycol mono- and di-fatty acid esters, such as propylene glycol laurate; propylene glycol caprylate / caprate; glycerol triacetate; sugar esters, lecithin, and combinations of any two or more thereof. In some embodiments, combinations of two or more surfactants are included in the disclosed nanoemulsions.

[0089] The amount of surfactant in the disclosed nanoemulsions can vary. In some embodiments, the amount of surfactant is about 2% by weight or more, about 3% by weight or more, about 4% by weight or more, about 5% by weight or more, about 6% by weight or more, about 7% by weight or more, about 8% by weight or more, or about 9% by weight or more. In some embodiments, the amount of surfactant is about 25% by weight or less, about 20% by weight or less, about 15% by weight or less, about 14% by weight or less, about 13% by weight or less, about 12% by weight or less, about 11% by weight or less, or about 10% by weight or less. Certain non-limiting ranges include, for example, about 2% by weight to about 25% by weight, about 5% by weight to about 20% by weight, or about 5% by weight to about 15% by weight. In some embodiments, the amount of surfactant is varied to obtain a suitable nanoemulsion exhibiting the properties outlined herein.

[0090] water As described herein, the disclosed nanoemulsions comprise water, and generally comprise water in its continuous phase. Water may be present, for example, as purified or ultrapure water, saline, buffered saline, or buffered aqueous phase. In some embodiments, water is the predominant component by weight (i.e., water is higher in mass than any of the other individual components). However, the total water content may be less than about 50% by weight of the nanoemulsion.

[0091] The water content of the nanoemulsion can vary depending on the desired properties. In some embodiments, the water content is about 10% to about 90% by weight based on the total weight of the nanoemulsion. In some embodiments, the water content is in an amount of about 15% to about 60% by weight, such as about 20% to about 50% by weight, about 25% to about 50% by weight, or about 30% to about 50% by weight based on the total weight of the nanoemulsion.

[0092] In some embodiments, one or more hydrophilic water-soluble components may be added to the water, including short chain monohydric, dihydric, and polyhydric alcohols (e.g., ethanol, benzyl alcohol, glycerol, propylene glycol, propylene carbonate, polyethylene glycols with average molecular weights of about 200 to about 10,000, diethylene glycol monoethyl ether, and combinations thereof). While in some embodiments, the nanoemulsions provided herein may include a monoalcohol (e.g., ethanol), the nanoemulsions may in some embodiments be formulated substantially free of monoalcohols (e.g., ethanol) or free of monoalcohols (e.g., ethanol). By "substantially free of monoalcohols" it is meant that no monoalcohols (e.g., ethanol) have been intentionally added to the nanoemulsion. For example, certain embodiments may be characterized as having less than 0.001% by weight monoalcohols or less than 0.0001% by weight or even 0% by weight monoalcohols.

[0093] Additional Optional Ingredients In addition to the components referenced herein above (i.e., active ingredients, surfactants, oil components, and water), the nanoemulsions provided herein can include any number of additional optional ingredients, including, but not limited to, humectants, antioxidants, sweeteners, taste modifiers, flavorants, colorants, salts, and combinations thereof.

[0094] Humectants can be added, for example, to reduce the total water activity of the oral product and thus further improve the stability and shelf life of the product (e.g., by helping to prevent microbial growth in the nanoemulsion). Examples of humectants include, but are not limited to, polyols (e.g., glycerin, 1,2-propanediol (propylene glycol), 1,3-propanediol, dipropylene glycol, sorbitol, xylitol, mannitol, and mixtures thereof). Particularly advantageous polyols are those that are miscible in water. In some embodiments, the nanoemulsion comprises a humectant selected from the group consisting of glycerin, propylene glycol, and mixtures thereof. Advantageously, in some embodiments, the humectant (e.g., glycerin) can also function as a preservative in the disclosed nanoemulsions, imparting microbial stability to the nanoemulsions. The humectant (e.g., glycerin and / or propylene glycol) may be present in an amount of from 0% to about 50% by weight of the nanoemulsion, such as from about 1% to about 40% by weight of the nanoemulsion, such as from about 10% to about 40% by weight, from about 20% to about 40% by weight of the oral product, or from about 20% to about 30% by weight of the nanoemulsion.

[0095] Antioxidants are particularly useful in some embodiments to stabilize active ingredients (e.g., cannabinoids or cannabinoid analogs) in the disclosed nanoemulsions. As used herein, the term "antioxidant" refers to a substance that can prevent or inhibit oxidation by terminating free radical reactions, slowing or preventing some types of cell damage. Antioxidants can be naturally occurring or synthetic and can be lipophilic or non-lipophilic. Naturally occurring antioxidants include those found in foods and botanical materials. Non-limiting examples of antioxidants include certain botanical materials, vitamins, polyphenols, and phenol derivatives.

[0096] Examples of botanical materials with antioxidant properties include, but are not limited to, acai berry, alfalfa, allspice, annatto seed, apricot kernel oil, basil, common mentha, monarda, black pepper, blueberry, borage seed oil, burdock, cacao, calamus root, cathartic vine, catuaba, cayenne pepper, chaga mushroom, chervil, cinnamon, dark chocolate, potato skin, grape seed, carrot, ginkgo biloba, St. John's wort, saw palmetto, green tea, black tea, black cohosh, cayenne, chamomile, cloves, cacao powder, cranberry, dandelion, grapefruit, honeybush, echinacea, garlic, evening primrose, feverfew, ginger, goldensea ash, and others. citrus fruit, hawthorn, hibiscus flower, gynostemma, kava, lavender, licorice, marjoram, milk thistle, mint, oolong tea, beet root, orange, oregano, papaya, mint, peppermint, red clover, rooibos (red or green), rose hips, rosemary, sage, clary sage, savory, spearmint, spirulina, slippery elm bark, sorghum high tannin bran, sorghum high tannin grain, urushi bran, comfrey leaves and root, wolfberries, gotu kola, thyme, turmeric, bearberry, valerian, wild yam root, mung bean, yacon root, yellow dock, yerba mate, yerba santa, bacopa monnieri. monniera, withania somnifera, Yamabushitake and Silybum marianum. Such botanical materials may be provided in fresh or dried form, in essential oils or in the form of extracts. Botanical materials (as well as their extracts) often contain compounds from various classes known to provide antioxidant benefits, such as minerals, vitamins, isoflavones, phytosterols, allyl sulfides, dithiolthiones, isothiocyanates, indoles, lignans, flavonoids, polyphenols and carotenoids.Examples of compounds found in botanical extracts or oils include ascorbic acid, peanut endocarp, resveratrol, sulforaphane, beta-carotene, lycopene, lutein, coenzyme Q, carnitine, quercetin, kaempferol, etc. See, e.g., Santhosh et al., Phytomedicine, 12 (2005), pp. 216-220, which is incorporated herein by reference.

[0097] Non-limiting examples of other suitable antioxidants include citric acid, vitamin E or a derivative thereof, tocopherol, epicatechol, epigallocatechol, epigallocatechol gallate, erythorbic acid, sodium erythorbate, ascorbyl esters (e.g., ascorbyl palmitate or ascorbyl stearate), sodium ascorbate, 4-hexylresorcinol, theaflavin, theaflavin monogallate A or B, theaflavin digallate, phenolic acids, glycosides, quercitrin, isoquercitrin, hyperosides, polyphenols, catechol, resveratrol, oleuropein, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tertiary butylhydroquinone (TBHQ), and combinations thereof.

[0098] When present, antioxidants are typically at a concentration of about 0.001% w / w to about 10% by weight based on the total weight of the nanoemulsion, e.g., about 0.001%, about 0.005%, about 0.01% w / w, about 0.05%, about 0.1% or about 0.5% to about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9% or about 10%.

[0099] Sweeteners can be optionally incorporated into the disclosed nanoemulsions in natural or artificial form or as a combination of artificial and natural sweeteners. Examples of natural sweeteners include fructose, sucrose, glucose, maltose, dextrose, fructose, mannose, galactose, lactose, stevia, honey, etc. Examples of artificial sweeteners include sucralose, isomaltulose, maltodextrin, saccharin, aspartame, acesulfame K, neotame, etc. In some embodiments, the sweetener comprises one or more sugar alcohols. Sugar alcohols are polyols derived from monosaccharides or disaccharides that have a partially or fully hydrogenated form. Sugar alcohols, for example, have from about 4 to about 20 carbon atoms and include erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and combinations thereof (e.g., hydrogenated starch hydrolysates). In some embodiments, stevia is particularly preferred as a sweetener in the disclosed nanoemulsions. Without intending to be limited by theory, it is believed that stevia, due to its lipophilic structure, is more likely to be present in the solubilized / dispersed phase (along with active ingredients), and therefore may improve sweetening properties, particularly with bitter active ingredients, which are particularly beneficial. When present, the sweetener or combination of sweeteners may comprise from about 0.1% to about 5% by weight of the nanoemulsion, for example, from about 0.1% to about 2% by weight of the nanoemulsion, or from about 0.1% to about 1% by weight of the nanoemulsion.

[0100] Taste modifiers (also referred to as "taste modifiers") can be optionally included to mask, for example, the bitter taste of one or more components of the nanoemulsion. For example, in some embodiments, the inclusion of a taste modifier can be useful to mask the bitter taste of the cannabinoid or cannabinoid analog of the nanoemulsion. Taste modifiers can improve the organoleptic properties of the nanoemulsions disclosed herein, and can function, for example, to mask, alter, mask or improve the flavor of the nanoemulsions described herein. Non-limiting examples of such taste modifiers include analgesic or anesthetic herbs, spices and flavors that produce a perceived sensation of cooling (e.g., menthol, eucalyptus, mint), warmth (e.g., cinnamon) or pain (e.g., capsaicin). Certain taste modifiers fall into two or more overlapping categories.

[0101] In some embodiments, the taste modifier modifies one or more of the following tastes: bitter, sweet, salty, or sour. In some embodiments, the taste modifier targets pain receptors. In some embodiments, the cannabinoid has a bitter taste, and the oral product includes a taste modifier that masks or blocks the perception of the bitter taste. In some embodiments, the taste modifier is a substance that targets pain receptors (e.g., vanilloid receptors) in the user's oral cavity, for example, masking the bitter taste of another component (e.g., a cannabinoid or cannabinoid analog). In some embodiments, the taste modifier is capsaicin. In some embodiments, the taste modifier is gamma aminobutyric acid (GABA), an amino acid referenced herein above with respect to amino acids. Studies in mice suggest that GABA may function in taste bud function in addition to synaptic inhibition. See, e.g., Dvoryanchikov et al., J Neurosci. 2011 Apr. 13;31(15):5782-91. Without wishing to be bound by theory, GABA can suppress the perception of certain tastes, such as bitterness. In some embodiments, the taste modifier is adenosine monophosphate (AMP). AMP is a naturally occurring nucleotide substance that can block bitter food flavors or enhance sweetness. It does not directly modify bitter flavors, but can modify the human perception of "bitterness" by blocking the associated receptor. In some embodiments, the taste modifier is lactisol. Lactisol is an antagonist of sweet taste receptors. Transiently blocking sweetness receptors can accentuate, for example, savory notes. One particularly useful taste modifier that affects the perception of bitterness associated with certain cannabinoids (e.g., CBD) is glycyrrhizinate, such as monoammonium glycyrrhizinate (MAG), sold, for example, under the trade name MAGNASWEET®. In some embodiments, MAG can further improve the aftertaste associated with certain sweeteners, such as stevia, that are incorporated into the nanoemulsion.Suitable MAG products include, but are not limited to, Magnasweet CM2 and Magnasweet CM1, as well as Magnasweet MM100, MM100F, MM110, MM110F, MM-100NF, MM100-EP, MM200F and MM210F, and the selection may depend at least in part on the flavor to be modified in the nanoemulsion.

[0102] When present, representative amounts of taste modifiers are about 0.01% by weight or more, about 0.05% by weight or more, or about 0.1% by weight or more, but typically comprise less than about 5% by weight of the total weight of the nanoemulsion (e.g., from about 0.01% to about 2% by weight, from about 0.05% to about 1% by weight, or from about 0.1% to about 0.5% by weight of the total weight of the nanoemulsion).

[0103] Optionally, flavorings can be included in the disclosed nanoemulsions. Flavorings can also be referred to as "flavoring materials," "flavors," "flavorings," or "flavoring agents." A wide range of flavorings are known. Flavorings are any flavorful or aromatic substance capable of modifying the sensory attributes associated with the nanoemulsion. Examples of sensory attributes that can be modified by flavorings include taste, texture, moistness, coolness / warmth, and / or aromaticity / aroma.

[0104] Flavoring agents may be natural or synthetic and their flavor characteristics may be described as, but not limited to, fresh, sweet, herbal, confectionery, floral, fruity, spicy, etc. Such flavoring agents may be utilized in some embodiments as concentrates or flavor packages. Some examples of flavoring agents include, but are not limited to, vanilla, vanillin, ethyl vanillin, cream, tea, coffee, fruit (e.g., apple, cherry, strawberry, peach, and citrus flavors including lime, lemon, and orange), maple, menthol, mint, peppermint, spearmint, mung bean, nutmeg, clove, lavender, cardamom, ginger, honey, anise, sage, rosemary, hibiscus, rose hips, yerba mate, guayusa, honeybush, rooibos, yerba santa, bacopa monnieri, ginkgo biloba, withania somnifera, cinnamon, eucalyptus, sandalwood, jasmine, cascarilla, coffee, cocoa / chocolate, licorice, and flavor and fragrance packages of types and characteristics traditionally used in cigarette, cigar, and pipe tobacco flavorings. Some examples of plant-derived compositions that may be suitable are disclosed in U.S. Patent No. 9,107,453 to Dube et al. and U.S. Patent Application Publication No. 2012 / 0152265, both of which are incorporated herein by reference in their entirety. The selection of such flavoring ingredients can vary based on factors such as the sensory attributes desired for the nanoemulsion, their solubility and other physiochemical properties. The present disclosure is intended to encompass any such additional ingredients that would be readily apparent to those skilled in the art of tobacco and tobacco-related or tobacco-derived products. See, for example, Gutcho, Tobacco Flavoring Substances Substances and Methods, Noyes Data Corp. (1972) and Leffingwell et al., Tobacco Flavoring for Smoking Products (1972). The disclosures of these documents are incorporated herein by reference in their entirety.It should be noted that the reference to flavors should not be limited to any single flavor described above, but may in fact represent a combination of one or more flavors. Additional flavors, flavorings, additives, and other possible enhancing components are described in U.S. Patent Application Publication No. 2019 / 0082735 to Phillips et al., which is incorporated herein by reference in its entirety.

[0105] In some embodiments, the flavoring agent is a plant extract. The extracts selected for use in certain embodiments of the disclosed methods and materials can be derived from a variety of species using a variety of techniques to produce extracts in a variety of usable forms, such as tobacco extracts or similar flavors derived from plants of the Nicotiana species. As used herein, the term "tobacco extract" refers to components that are separated from, removed from, or derived from tobacco using tobacco extraction processing conditions and techniques. Purified extracts of tobacco or other botanicals can be specifically used. Typically, tobacco extracts are obtained using a solvent, such as an aqueous natural solvent (e.g., water) or a solvent having an organic solvent (e.g., an alcohol, such as ethanol, or an alkane, such as hexane). Thus, the extracted tobacco components are removed from the tobacco and separated from the non-extracted tobacco components, and for the extracted tobacco components present in the solvent, (i) the solvent can be removed from the extracted tobacco components, or (ii) a mixture of the extracted tobacco components and the solvent can be used in this manner.Examples of types of tobacco extracts, tobacco essences, solvents, tobacco extraction processing conditions and techniques, and tobacco extract collection and isolation procedures are described in Australian Patent No. 276,250 to Schachner; U.S. Patent No. 2,805,669 to Meriro; U.S. Patent No. 3,316,919 to Green et al.; U.S. Patent No. 3,398,754 to Tughan; U.S. Patent No. 3,424,171 to Rooker; U.S. Patent No. 3,476,118 to Luttich; U.S. Patent No. 4,150,677 to Osborne; U.S. Patent No. 4,131,117 to Kite; U.S. Patent No. 4,506,682 to Muller; U.S. Patent No. 4,986,286 to Roberts et al.; U.S. Patent No. 5,005,593 to Fagg; and U.S. Patent No. 5,065,775 to Fagg. No. 5,060,669 to White et al.; U.S. Pat. No. 5,074,319 to White et al.; U.S. Pat. No. 5,099,862 to White et al.; U.S. Pat. No. 5,121,757 to White et al.; U.S. Pat. No. 5,131,415 to Munoz et al.; U.S. Pat. No. 5,230,354 to Smith et al.; U.S. Pat. No. 5,235,992 to Sensabaugh; U.S. Pat. No. 5,243,999 to Smith; U.S. Pat. No. 5,301,694 to Raymond; U.S. Pat. No. 5,318,050 to Gonzalez-Parra et al.; U.S. Pat. No. 5,435,325 to Clapp et al.; and U.S. Pat. No. 5,445,169 to Brinkley et al., all of which are incorporated by reference in their entireties.

[0106] In some embodiments, the perfume ingredients that can be incorporated into the nanoemulsions provided herein include one or more of alcohols, aldehydes, aromatic hydrocarbons, ketones, esters, terpenes, terpenoids, and trigeminal sensates. Non-limiting examples of aldehydes include vanillin, ethyl vanillin, p-anisaldehyde, hexanal, furfural, isovaleraldehyde, cuminaldehyde, benzaldehyde, and citronellal. Non-limiting examples of ketones include 1-hydroxy-2-propanone and 2-hydroxy-3-methyl-2-cyclopentenone-1-one. Non-limiting examples of esters include allyl hexanoate, ethyl heptanoate, ethyl hexanoate, isoamyl acetate, and 3-methylbutyl acetate. Non-limiting examples of terpenes include sabinene, limonene, gamma-terpinene, beta-farnesene, nerolidol, thujone, myrcene, geraniol, nerol, citronellol, linalool, and eucalyptol.

[0107] In some embodiments, the flavoring agent comprises menthol, spearmint, and / or peppermint. In some embodiments, the flavoring agent comprises cucumber, blueberry, citrus fruit, and / or red berry flavor ingredients. In some embodiments, the flavoring agent comprises eugenol. In some embodiments, the flavoring agent comprises flavor ingredients extracted from tobacco. In some embodiments, the flavoring agent comprises flavor ingredients extracted from cannabis.

[0108] In some embodiments, the flavoring agent may include sensates, which are intended to achieve somatosensory sensations that are usually chemically induced and perceived by stimulation of the fifth cranial nerve (trigeminal nerve) in addition to or instead of the aroma or taste nerves, and may include agents that provide heating, cooling, tingling, and numbing effects. A suitable agent for heating effects may be, but is not limited to, vanillyl ethyl ether, and a suitable cooling agent may be, but is not limited to, eucoliptol or WS-3. The flavoring agent, including the extract, may be provided in various forms, for example, in liquid form or substantially solid (e.g., powder or pellet type) form.

[0109] The amount of flavoring agent present in the nanoemulsions of the present disclosure may vary. When the nanoemulsion includes one or more flavoring agents, the content of such flavoring agents is generally at most about 10% by weight of the nanoemulsion, for example, at most about 5%, at most about 2%, or at most about 1% by weight. For example, the flavoring agent may be present in an amount of about 0.01%, about 0.05%, about 0.1%, or about 0.5% to about 2%, about 5%, about 8%, or about 10% by weight of the final nanoemulsion.

[0110] Colorants can optionally be utilized in amounts sufficient to provide the nanoemulsion with desired physical attributes. Examples of colorants include various dyes and pigments, such as caramel color and titanium dioxide. The amount of colorant utilized in the product can vary, but when present, is typically up to about 3% by weight based on the total weight of the nanoemulsion, such as about 0.01%, about 0.1%, about 0.5%, or about 1% to about 3% by weight.

[0111] In some embodiments, nanoemulsions include salts (e.g., alkali metal salts) that are typically utilized in amounts sufficient to provide the product with the desired sensory attributes. In some embodiments, certain salts may also function as electrolytes or act synergistically with electrolytes. For example, without wishing to be bound by theory, sodium citrate may provide a source of both sodium (an electrolyte) and aid in the absorption of other electrolytes and water. Non-limiting examples of suitable salts include sodium chloride, potassium chloride, ammonium chloride, powdered salt, sodium acetate, sodium citrate, and the like. In some embodiments, the salt is sodium chloride, ammonium chloride, sodium citrate, or a combination thereof. In some embodiments, the salt is sodium chloride.

[0112] When present, representative amounts of salt are about 0.1% by weight or more, about 0.5% by weight or more, about 1.0% by weight or more, or about 1.5% by weight or more, but typically comprise about 10% by weight or less, or about 7.5% by weight or less, or about 5% by weight or less (e.g., about 0.5 to about 5% by weight) of the total weight of the nanoemulsion. In specific embodiments, the product comprises sodium chloride in an amount of about 1 to about 3% by weight based on the total weight of the nanoemulsion.

[0113] The disclosed nanoemulsions can be formed in a variety of ways. In general, a nanoemulsion can be produced by combining and mixing / emulsifying its components. The components can be mixed in a variety of orders, and the mixing / emulsification can be facilitated in a variety of ways.

[0114] In one embodiment, the disclosed nanoemulsion is prepared by combining the oil-soluble and water-soluble components separately. A surfactant and a second oil (e.g., lecithin) are then added to the aqueous mixture, which is then mixed using a high shear mixer. The oil-soluble component mixture is slowly added to the aqueous / surfactant mixture under the same high shear mixing conditions. The entire mixture is then exposed to energy (e.g., via sonication) to reduce the droplet size.

[0115] Both high-energy and low-energy emulsification methods are known for producing nanoemulsions. Suitable non-limiting high-energy emulsification methods include, but are not limited to, high-energy stirring, ultrasonic emulsification, high-pressure homogenization, microfluidization, and membrane emulsification. Suitable non-limiting low-energy emulsification methods include, but are not limited to, phase inversion temperature, emulsion inversion point, and spontaneous emulsification.

[0116] The emulsions described herein advantageously exhibit high stability. High physical stability and shelf life can be evidenced, for example, by the maintenance of similar particle (droplet / micelle) sizes within the nanoemulsion over time. Unstable formulations tend to grow in micelle size over time and ultimately phase separate over time. Thus, high physical stability and shelf life can be assessed, for example, by comparing particle sizes over time and / or by physical observation (i.e., examining to determine whether any significant phase separation occurs within the nanoemulsion, for example, via aggregation and / or creaming of the dispersed phase).

[0117] In some embodiments, accelerated aging studies can be used as an indication of good shelf life and high physical stability.For example, in some embodiments, the nanoemulsions described herein can undergo accelerated aging studies (e.g., as described in ASTM D1791-93) with small changes in droplet (dispersed phase) size.For example, in some embodiments, the disclosed nanoemulsions exhibit a Z-average diameter of droplets of about 90 nm or less or about 100 nm or less even after aging.

[0118] In some embodiments, the shelf life of the nanoemulsion can be at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, or at least about 12 months. As used herein, "shelf life" refers to the period during which no visible microbial growth is observed in the product and there is no deterioration in the appearance and / or taste of the nanoemulsion (e.g., as indicated by observable creaming / phase separation and / or significant growth in particle size of the nanoemulsion droplets).

[0119] Tinctures The disclosed nanoemulsions can be used directly (i.e., without further modification) as a tincture of an active ingredient. When used directly, the tincture can be used in various amounts and at various times per day. In some embodiments, a subject (human or animal) can take 2-5 mL of the tincture 1-5 times per day. Most typically, the tincture is used orally. In some embodiments, the tincture is placed in a bottle with a dropper, and the subject can apply the tincture via the dropper to the mouth, such as the tongue or cheek (so that the active ingredient is absorbed through the mucous membrane / buccal side), swallow (so that the active ingredient is taken enterally / by intestinal absorption), or apply it under the tongue (so that the active ingredient is absorbed through the mucous membrane / sublingually). In some embodiments, the subject adds the tincture to a food or beverage, for example, at the time of ingestion.

[0120] Other oral products In some embodiments, the disclosed nanoemulsions can be further formulated as or for inclusion within other oral products, for example, the nanoemulsions can be formulated as drinkable shots or for inclusion within, for example, liquid-filled capsules.

[0121] Oral products in the form of shots are provided, for example, by diluting the nanoemulsion provided herein above. Shots can be provided / packaged for consumption as a single shot (e.g., about 25 mL to about 75 mL) or in a larger volume that can be used as multiple shots. Typically, no specific processing method is required, and simple mixing is sufficient to provide a shot in some embodiments. The amount of dilution can vary, and in some embodiments, about 0.5% to about 5% by weight of the shot is included in the nanoemulsion described herein above.

[0122] The composition of the remainder of the shot may vary. In some embodiments, the remaining components comprise or consist essentially of water, as well as one or more preservatives, one or more pH adjusters / buffers (e.g., which may function to inhibit microbial growth in the liquid), and / or one or more antioxidants. In some embodiments, the shot may further comprise one or more sweeteners (e.g., in an amount of up to about 2% by weight) and / or one or more flavorings (e.g., in an amount of up to about 3% by weight) as referenced above. In some embodiments, the shot may further comprise one or more terpenes. In some embodiments, such shots are considered non-alcoholic, although in other embodiments, an amount of monoalcohol may optionally be included in the disclosed shots (replacing some or all of the water). In some embodiments, the shots are carbonated, which may further improve the stability of the product by removing oxygen. Additional flavors, colors, sweeteners, and the like may be included in the shots provided herein in some embodiments.

[0123] Examples of pH adjusters and buffering agents that can be used include, but are not limited to, metal hydroxides (e.g., alkali metal hydroxides, such as sodium hydroxide and potassium hydroxide) and other alkali metal buffers, such as metal carbonates (e.g., potassium carbonate or sodium carbonate) or metal bicarbonates, such as sodium bicarbonate. Non-limiting examples of suitable buffers include alkali metal acetates, glycinates, phosphates, glycerophosphates, citrates, carbonates, bicarbonates, borates, or mixtures thereof. In certain embodiments, the buffering agent comprises a sodium citrate / citric acid buffer system. The buffering agent is typically present in an amount of less than about 5% by weight based on the weight of the shot agent, for example, about 0.1% to about 5% by weight, for example, about 0.01% to about 1% by weight, about 0.01% to about 0.5% by weight, or about 0.01% to about 0.1% by weight based on the total weight of the shot agent.

[0124] Examples of preservatives include, but are not limited to, potassium sorbate, sodium benzoate, calcium propionate, combinations thereof, and the like. In some embodiments, the preservatives include, for example, benzyl alcohol, cetylpyridine chloride, glycerin, methylparaben, propylene glycol, propyleneparaben, potassium sorbate, sodium benzoate, sorbic acid, sodium propionate, or combinations thereof. In some embodiments, such preservatives can help reduce the water activity of the shot formulation, further improving the stability and shelf life of the shot formulation. In certain embodiments, the disclosed shot formulations include sodium benzoate and potassium sorbate as preservatives. A preservative (or preservatives) is typically present in an amount of less than about 5% by weight based on the weight of the shot formulation, for example, about 0.1% to about 5% by weight based on the total weight of the shot formulation, for example, about 0.01% to about 1% by weight, about 0.01% to about 0.5% by weight, or about 0.05% to about 0.5% by weight.

[0125] Examples of antioxidants include, but are not limited to, those referenced above for nanoemulsions. In some embodiments, the shot formulations described herein include both a water-soluble antioxidant (e.g., sodium ascorbate) and an oil-soluble antioxidant (e.g., vitamin E). The antioxidant (or antioxidants) are typically present in an amount of less than about 5% by weight based on the weight of the shot formulation, for example, in an amount of about 0.1% to about 5% by weight, for example, about 0.01% to about 1% by weight, about 0.01% to about 0.5% by weight, or about 0.05% to about 0.5% by weight based on the total weight of the shot formulation.

[0126] Similar to the nanoemulsions / tinctures referenced above, the shots provided herein, in some embodiments, can exhibit a shelf life of at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, or at least about 12 months.

[0127] Many modifications and other embodiments of the invention will come to mind to one skilled in the art to which this invention pertains having the benefit of the teachings presented in the foregoing description. It is to be understood, therefore, that the invention is not limited to the specific embodiments disclosed, but that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation. EXAMPLES

[0128] Aspects of the present invention will be more fully described by the following examples, which are presented to illustrate certain specific aspects of the invention and should not be construed as limiting thereof.

[0129] Example 1: Preparation of nanoemulsion Nanoemulsions containing the ingredients listed in Table 1 were prepared by the following method: The oil-soluble ingredients were combined and the water-soluble ingredients were combined separately. Poly oxyl 40 stearate and canola lecithin were then added to the aqueous mixture, which was then mixed using a high shear mixer. The oil-soluble ingredient mixture was slowly added to the aqueous / surfactant mixture under the same high shear mixing conditions, forming droplets in the continuous aqueous phase with a diameter of about 200 nm. The entire mixture was then subjected to ultrasonic treatment to reduce the droplet size and obtain the desired nanoemulsion.

[0130] [Table 1]

[0131] The nanoemulsion was evaluated by dynamic light scattering to determine the average micelle size (diameter) within the liquid, e.g., as shown in Figure 1. Evaluation showed that the nanoemulsion prepared had a Z-average particle size of 61.66 nm, indicating high bioavailability.

[0132] The nanoemulsions were then subjected to accelerated aging studies (via exposing the nanoemulsions to elevated temperatures or gravity / centrifugation) over a period of time to monitor micelle size over time. This study uses the physical stability of the emulsion at elevated temperatures to predict the stability of the emulsion at room temperature over time. The nanoemulsions were aged and tested according to ASTM D1791-93, an industry standard for accelerated aging studies. The standard concludes that if an oil-in-water emulsion is physically stable at 52°C for 30 days, it is predicted to have one year of stability at room temperature. As shown in Figure 2, after exposure to aging conditions with ASTM D1791-93, the nanoemulsions prepared had a Z-average micelle size of 88.1 nm, demonstrating physical stability and bioavailability for a one-year product shelf life.

[0133] The nanoemulsions were also monitored by physical observation over time. The formulations in Table 1 above do not phase separate over time, for example, over a period of at least three months. In contrast, nanoemulsions prepared with sunflower lecithin powder, soy lecithin powder, or purified phosphatidylcholine instead of (crude, unrefined) canola lecithin began to show phase separation over time (as indicated by creaming of the nanoemulsion at the top of the vial containing the nanoemulsion).

[0134] [Example 2] Preparation of shot agent Shots containing the ingredients listed in Table 2 were prepared by simple mixing. The nanoemulsions were easily rehydrated by mixing, and additional ingredients were added (i.e., preservatives and a buffer system to modify the pH). In some embodiments, one or more antioxidants are also added (e.g., vitamin E, which is soluble in the oil phase, and sodium ascorbate, which is soluble in the water phase).

[0135] [Table 2]

[0136] The shot formulation was evaluated as the nanoemulsion above and was found to have the same micelle size as the nanoemulsion.

[0137] The first sample of the shot formulation underwent an accelerated aging experiment at 70° C. for two weeks. Turbidity measurements of the shot formulation were performed using a turbidimeter over a two week period and showed an average turbidity of 210±20 NTU. Turbidity is an indication of micelle size with time, and consistent turbidity (as shown in this study) indicates physical stability of the micelles.

[0138] A second sample of the shot was exposed to ASTM D1791-93 aging conditions (52°C for 30 days). The prepared shot had a Z-average micelle size of 62 nm after aging and demonstrated physical stability and bioavailability for a one year product shelf life, as shown in Figure 3. The USP 51 microbial challenge test was used to determine whether the preservatives in the shot formulation were sufficiently robust to protect against microbial contamination. The shot formulation uses the preservatives sodium benzoate and potassium sorbate in a sodium citrate / citric acid buffer system to inhibit microbial growth. The USP 51 microbial challenge involves inoculating the CBD shot with the microorganisms Pseudomonas aeruginosa, E. Coli, Staphylococcus aureus, Candida albicans, and Aspergillus brasiliensis on day 0. The microbial counts of the shot are measured over a 28 day period. The results are shown in Table 3 below and indicate that the preservative was highly successful in killing and inhibiting the growth of the microorganisms in the shot.

[0139] [Table 3]

[0140] Although some exemplary embodiments of the present invention are described herein, it should be apparent to those skilled in the art that the foregoing is merely illustrative and not limiting, and is presented by way of example only. Many modifications and other embodiments are within the scope of one of ordinary skill in the art and are contemplated to be included within the scope of the present invention. In particular, while many of the examples presented herein include specific combinations of method steps or system elements, it should be understood that these steps and these elements can be combined in other ways to achieve the same purpose.

[0141] Moreover, those skilled in the art should understand that the parameters and configurations described herein are examples only, and that the actual parameters and / or configurations will depend on the specific application in which the systems and techniques of the present invention are used. Those skilled in the art should also be able to recognize, or ascertain, using no more than routine experimentation, equivalents to the specific embodiments of the present invention. Accordingly, it should be understood that the embodiments described herein are presented by way of example only, and that within the scope of any appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described.

[0142] The phraseology and terminology used herein are for the purpose of explanation and should not be considered limiting. As used herein, the term "plurality" refers to two or more items or components. The terms "comprising," "including," "carrying," "having," "containing," and "involving" are open-ended terms, i.e., meaning "including, but not limited to," whether in writing or in claims or otherwise. Thus, the use of such terms is meant to encompass the items listed below and their equivalents as well as additional items. Only the transitional phrases "consisting of" and "consisting essentially of" are closed or semi-closed transitional phrases, respectively, for any claim. The use of ordinal terms such as "first," "second," "third," etc. in the claims to modify claim elements do not, by themselves, imply any priority, precedence, or ordering of one claim element over another claim element, or the temporal order in which acts of a method are performed, but are used solely as markers to distinguish one claim element having a particular name from another element having the same name (except for the use of ordinal terms) to distinguish the claim elements.

Claims

1. A nanoemulsion comprising a cannabinoid and / or a cannabinoid analog, a first oil, a second oil, and water wherein the cannabinoid or cannabinoid analog is present in an amount of about 1% by weight or more. A nanoemulsion.

2. The nanoemulsion according to claim 1, wherein the cannabinoid or cannabinoid analog is present in an amount of about 2% by weight or more.

3. The nanoemulsion according to claim 1, wherein the cannabinoid or cannabinoid analog is present in an amount of about 1% by weight to about 4% by weight.

4. The nanoemulsion according to claim 1, wherein the cannabinoid or cannabinoid analog is present in an amount of about 2% by weight to about 3% by weight.

5. The nanoemulsion according to claim 1, wherein the cannabinoid or cannabinoid analog is selected from the group consisting of cannabigerol, cannabinchromene, cannabidiol, tetrahydrocannabinol, cannabinol, cannabinodiol, and combinations thereof.

6. The nanoemulsion according to claim 1, wherein the cannabinoid or cannabinoid analog is selected from the group consisting of cannabigerol (CBG), cannabinchromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabinchromvarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabinotriol (CBO), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarinic acid (THCVA), and combinations thereof.

7. The nanoemulsion according to claim 1, wherein the cannabinoid or cannabinoid analog comprises cannabidiol (CBD).

8. ​ The nanoemulsion according to claim 1, wherein the cannabinoid or cannabinoid analog is selected from the group consisting of yangonin, alpha - amyrin or beta - amyrin (also classified as a terpene), cyanidin, curcumin (turmeric), catechin, quercetin, salvianolin A, N - acyl ethanolamine, N - alkylamide lipid, and combinations thereof.

9. The nanoemulsion according to claim 1, wherein the first oil contains sunflower oil.

10. The nanoemulsion according to claim 1, wherein the second oil contains lecithin.

11. The nanoemulsion according to claim 10, wherein the second oil is canola lecithin.

12. The nanoemulsion according to claim 10, wherein the weight ratio of the second oil to the first oil is about 1.5 or more.

13. The nanoemulsion according to claim 10, wherein the weight ratio of the second oil to the first oil is about 1.5 to about 3.

14. The nanoemulsion according to claim 1, further comprising a surfactant.

15. The nanoemulsion according to claim 14, wherein the surfactant is polyoxyethylene stearate.

16. The nanoemulsion according to claim 1, further comprising one or more natural or artificial sweeteners.

17. The nanoemulsion according to claim 16, wherein the natural or artificial sweetener is selected from the group consisting of saccharin, acesulfame K, aspartame, sucralose, isomalt, lactose, mannitol, sorbitol, xylitol, sucrose, stevia, and combinations thereof.

18. The nanoemulsion according to claim 17, wherein the natural or artificial sweetener contains stevia.

19. The nanoemulsion according to claim 1, further comprising a bitterness inhibitor.

20. The nanoemulsion according to claim 19, wherein the bitterness inhibitor is glycyrrhizic acid or a salt thereof.

21. The nanoemulsion according to claim 1, further comprising an antioxidant.

22. The nanoemulsion according to claim 21, wherein the antioxidant is selected from the group consisting of citric acid, vitamin E, tocopherol, epicatechol, epigallocatechol, epigallocatechin gallate, erythorbic acid, sodium erythorbate, ascorbyl palmitate, ascorbyl stearate, sodium ascorbate, ascorbic acid, 4-hexylresorcinol, theaflavin, theaflavin monogallate A or B, theaflavin digallate, phenolic acid, glycoside, quercitrin, isoquercitrin, hyperoside, polyphenol, catechol, resveratrol, oleuropein, butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), tertiary butylhydroquinone (TBHQ), and combinations thereof.

23. The nanoemulsion according to claim 1, further comprising a wetting agent.

24. The nanoemulsion according to claim 23, wherein the wetting agent is a polyol.

25. The nanoemulsion according to claim 23, wherein the wetting agent comprises glycerin, propylene glycol, 1,3-propanediol, dipropylene glycol, sorbitol, xylitol, mannitol, or combinations thereof.

26. The nanoemulsion according to claim 1, substantially free of monoalcohol.

27. The nanoemulsion according to any one of claims 1 to 26, comprising a dispersed phase in water, the dispersed phase having an average droplet size of about 100 nm or less.

28. The nanoemulsion according to any one of claims 1 to 26, exhibiting physical stability for 6 months or more.

29. The nanoemulsion according to claim 28, exhibiting physical stability for 12 months or more.

30. An oral product in the form of a sizing agent, consisting essentially of the nanoemulsion according to any one of claims 1 to 26.

31. An oral product in the form of a shot, comprising the nanoemulsion according to any one of claims 1 to 26 diluted in water.

32. The oral product according to claim 31, further comprising at least one buffering agent, at least one preservative, at least one antioxidant, or any combination thereof.

33. The oral product according to claim 31, wherein the shot exhibits physical stability for 6 months or more.

34. The oral product according to claim 31, wherein the injection agent exhibits physical stability for 12 months or longer.

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