Oral products containing cannabinoids

Abstract

The present disclosure provides nanoemulsions comprising an oil phase containing at least one cannabinoid and an aqueous phase, wherein at least one of the oil phase and the aqueous phase comprises one or more emulsifiers, and wherein the zeta potential of the nanoemulsion is less than about -10 mV. Methods for preparing such nanoemulsions are further provided.

Description

Technical Field

[0001] The present disclosure relates to a method for preparing a nanoemulsion, as well as to a nanoemulsion, an oral product, a pouch-packed oral product, and a package containing said nanoemulsion. In particular, the present disclosure relates to a method for preparing a product for human use. The product is configured for oral use and delivers an active ingredient during use. Such products include cannabinoids or products derived from cannabinoids.

Background Art

[0002] Tobacco can be enjoyed in so-called "smokeless" forms. Particularly popular smokeless tobacco products are used by inserting several forms of processed tobacco or tobacco-containing formulations into the user's mouth. Conventional forms of such smokeless tobacco products include moist snuff, snus, and chewing tobacco. These are typically formed almost entirely from particulate, granular, or shredded tobacco and are either portioned out by the user or presented to the user in individual portions such as disposable pouches or bags. Other conventional forms of smokeless products include compressed or aggregated forms such as plugs, tablets, or pellets. Alternative product forms such as tobacco-containing gum and mixtures of tobacco with other plant materials are also known.For example, U.S. Patent Nos. 1,376,586 (Schwartz), 4,513,756 (Pittman et al.), 4,528,993 (Sensabaugh, Jr. et al.), 4,624,269 (Story et al.), 4,991,599 (Tibbetts), 4,987,907 (Townsend), and 5,092,3 are incorporated herein by reference. Patent No. 52 (Sprinkle, III et al.), No. 5,387,416 (White et al.), No. 6,668,839 (Williams), No. 6,834,654 (Williams), No. 6,953,040 (Atchley et al.), No. 7,032,601 (Atchley et al.) and No. 7,694,686 (Atchley et al.), U.S. Patent Application Publication No. 2004 / 0020503 (Will iams), same No. 2005 / 0115580 (Quinter et al.), same No. 2006 / 0191548 (Strickland et al.), same No. 2007 / 0062549 (Holton, Jr. et al.), same No. 2007 / 0186941 (Holton, Jr. et al.), same No. 2007 / 0186942 (Strickland et al.), same No. 2008 / 0029110 (Dube et al.), same No. 2008 / 0029 See the types, components, and processing methods of smokeless tobacco formulations described in No. 116 (Robinson et al.), No. 2008 / 0173317 (Robinson et al.), No. 2008 / 0209586 (Neilsen et al.), No. 2009 / 0065013 (Essen et al.); and No. 2010 / 0282267 (Atchley), and WO2004 / 095959 (Arnarp et al.).

[0003] More smokeless tobacco product configurations combining tobacco materials with various binders and fillers have been proposed recently, and examples of product forms including drops, lozenges, gels, and extruded materials can be seen. For example, U.S. Patent Application Publications 2008 / 0196730 (Engstrom et al.), 2008 / 0305216 (Crawford et al.), 2009 / 0293889 (Kumar et al.), 2010 / 0291245 (Gao et al.), 2011 / 0139164 (Mua et al.), 2012 / 0037175 (Cantrell et al.), 2012 / 0055494 (Hunt et al.), 2012 / 0138073 (Cantrell et al.), each incorporated herein by reference. See the product types listed in Issues 2012 / 0138074 (Cantrell et al.), 2013 / 0074855 (Holton, Jr.), 2013 / 0074856 (Holton, Jr.), 2013 / 0152953 (Mua et al.), 2013 / 0274296 (Jackson et al.), 2015 / 0068545 (Moldoveanu et al.), 2015 / 0101627 (Marshall et al.), and 2015 / 0230515 (Lampe et al.).

[0004] All-white snus portions are gaining popularity, becoming a visually appealing alternative to traditional snus. These recent "white" pouch products may or may not contain bleached tobacco. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] U.S. Patent No. 1,376,586 [Patent Document 2] U.S. Patent No. 4,513,756 [Patent Document 3] U.S. Patent No. 4,528,993 [Patent Document 4] U.S. Patent No. 4,624,269 [Patent Document 5] U.S. Patent No. 4,991,599 [Patent Document 6] U.S. Patent No. 4,987,907 [Patent Document 7] U.S. Patent No. 5,092,352 [Patent Document 8] U.S. Patent 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] U.S. Patent Application Publication No. 2004 / 0020503 [Patent Document 15] U.S. Patent Application Publication No. 2005 / 0115580 [Patent Document 16] U.S. Patent Application Publication No. 2006 / 0191548 [Patent Document 17] U.S. Patent Application Publication No. 2007 / 0062549 [Patent Document 18] U.S. Patent Application Publication No. 2007 / 0186941 [Patent Document 19] U.S. Patent Application Publication No. 2007 / 0186942 [Patent Document 20] U.S. Patent Application Publication No. 2008 / 0029110 [Patent Document 21] U.S. Patent Application Publication No. 2008 / 0029116 [Patent Document 22] U.S. Patent Application Publication No. 2008 / 0173317 [Patent Document 23] U.S. Patent Application Publication No. 2008 / 0209586 [Patent Document 24] U.S. Patent Application Publication No. 2009 / 0065013 [Patent Document 25] U.S. Patent Application Publication No. 2010 / 0282267 [Patent Document 26] International Publication No. 2004 / 095959 [Patent Document 27] U.S. Patent Application Publication No. 2008 / 0196730 [Patent Document 28] U.S. Patent Application Publication No. 2008 / 0305216 [Patent Document 29] U.S. Patent Application Publication No. 2009 / 0293889 [Patent Document 30] U.S. Patent Application Publication No. 2010 / 0291245 [Patent Document 31] U.S. Patent Application Publication No. 2011 / 0139164 [[ID=3s]][Patent Document 32] U.S. Patent Application Publication No. 2012 / 0037175 [Patent Document 33] U.S. Patent Application Publication No. 2012 / 0055494 [Patent Document 34] U.S. Patent Application Publication No. 2012 / 0138073 [Patent Document 35] U.S. Patent Application Publication No. 2012 / 0138074 [Patent Document 36] U.S. Patent Application Publication No. 2013 / 0074855 [Patent Document 37] U.S. Patent Application Publication No. 2013 / 0074856 [Patent Document 38] U.S. Patent Application Publication No. 2013 / 0152953 [Patent Document 39] o U.S. Patent Application Publication No. 2013 / 0274296 [Patent Document 40] U.S. Patent Application Publication No. 2015 / 0068545 [Patent Document 41] U.S. Patent Application Publication No. 2015 / 0101627 [Patent Document 42] U.S. Patent Application Publication No. 2015 / 0230515 [Overview of the project] [Problems that the invention aims to solve]

[0006] It would be desirable to provide products designed for oral use that deliver active ingredients to consumers in an enjoyable form, such as a pouch-packaged product. [Means for solving the problem]

[0007] (Brief summary) According to some embodiments described herein, a method for preparing a nanoemulsion containing at least one cannabinoid, (a) A step of providing an oil phase containing at least one cannabinoid, (b) A step of providing an aqueous phase, (c) A process of combining the oil phase and the aqueous phase to form a macroemulsion, (d) Process to form nanoemulsions by processing macroemulsions. Includes, At least one of the oil phase and the aqueous phase contains one or more emulsifiers. A method is provided.

[0008] According to some embodiments described herein, a nanoemulsion comprising at least one cannabinoid, (a) A step of providing an oil phase containing at least one cannabinoid, (b) A step of providing an aqueous phase, (c) A process of combining the oil phase and the aqueous phase to form a macroemulsion, (d) Process to form nanoemulsions by processing macroemulsions. Includes, At least one of the oil phase and the aqueous phase contains one or more emulsifiers. Nanoemulsions obtained or obtainable by the method are provided.

[0009] According to some embodiments described herein, (a) an oil phase containing at least one cannabinoid, (b) Water phase A nanoemulsion containing, At least one of the oil phase and the aqueous phase contains one or more emulsifiers. The zeta potential of the nanoemulsion is less than approximately -10mV. Nanoemulsions are provided.

[0010] According to some embodiments described herein, an oral product comprising a nanoemulsion containing at least one cannabinoid, wherein the nanoemulsion is (a) obtained or obtainable by the methods defined herein, or (b) (i) an oil phase containing at least one cannabinoid, (ii) aqueous phase Includes, At least one of the oil phase and the aqueous phase contains one or more emulsifiers. The zeta potential of the nanoemulsion is less than approximately -10mV. Oral products are provided.

[0011] According to some embodiments described herein, pouched oral products are provided, including a saliva-permeable pouch and an oral product as defined herein incorporated within the pouch.

[0012] According to some embodiments described herein, a package containing an oral product as defined herein, or at least one pouch-packaged oral product as defined herein, is provided.

[0013] This disclosure includes, but is not limited to, the following embodiments.

[0014] Embodiment 1: A method for preparing a nanoemulsion containing at least one cannabinoid, comprising the steps of (a) providing an oil phase containing at least one cannabinoid, (b) providing an aqueous phase, (c) combining the oil phase and the aqueous phase to form a macroemulsion, and (d) processing the macroemulsion to form a nanoemulsion, wherein at least one of the oil phase and the aqueous phase contains one or more emulsifiers.

[0015] Embodiment 2: (d) The method according to Embodiment 1, further comprising the step of ultrasonically treating a macroemulsion to form a nanoemulsion.

[0016] Embodiment 3: The method according to Embodiment 1 or 2, wherein (d) includes the step of processing a macroemulsion in a homogenizer to form a nanoemulsion.

[0017] Embodiment 4: The method according to Embodiment 3, wherein the homogenizer is a high-pressure valve homogenizer, an ultrasonic jet homogenizer, or an ultrasonic probe homogenizer.

[0018] Embodiment 5: The method according to Embodiment 3 or 4, wherein the macroemulsion passes through the homogenizer at a flow rate of approximately 100 mL / min to approximately 9 L / min.

[0019] Embodiment 6: The method according to any one of Embodiments 3 to 5, wherein the macroemulsion passes through a homogenizer at a temperature of approximately 20°C to approximately 40°C.

[0020] Embodiment 7: The method according to any one of Embodiments 1 to 6, wherein Embodiment 7(d) includes the step of processing a macroemulsion in a microfluidizer to form a nanoemulsion.

[0021] Embodiment 8: The method according to any one of Embodiments 1 to 7, further comprising the step of (a) (1) heating the oil phase to a temperature of at least about 50°C and dissolving at least one cannabinoid in the oil phase.

[0022] Embodiment 9: The method according to Embodiment 8, wherein (a)(1) includes a step of heating the oil phase to a temperature of about 60°C to about 85°C.

[0023] Embodiment 10: The method according to any one of Embodiments 1 to 9, wherein the weight ratio of oil to at least one cannabinoid is about 1:1 to about 10:1.

[0024] Embodiment 11: The method according to any one of Embodiments 1 to 10, further comprising the step of (b)(1) combining the aqueous phase with one or more emulsifiers.

[0025] Embodiment 12: The method according to Embodiment 11, wherein (b)(1) includes a step of combining the aqueous phase with one or more emulsifiers by high-shear mixing.

[0026] Embodiment 13: The method according to any one of Embodiments 1 to 12, wherein (c) includes a step of combining an oil phase and an aqueous phase by high-shear mixing to form a macroemulsion.

[0027] Embodiment 14:(c) is the method according to any one of Embodiments 1 to 13, wherein the step is to combine the oil phase and the aqueous phase in a weight ratio of about 2:1 to about 1:10.

[0028] Embodiment 15: The method according to any one of Embodiments 1 to 14, wherein the total HLB value of one or more emulsifiers is approximately 11 to approximately 15.

[0029] Embodiment 16: One or more emulsifiers include stearamide MEA, glyceryl stearate (and) PEG-100 stearate, polysorbate 85, PEG-7 olive, cetearyl glucoside, PEG-8 oleate, polyglyceryl-3 methyl glucose distearate, oleth-10, oleth-10 / polyoxyl-10 oleyl ether NF, ceteth-10, PEG-8 laurate, cocamide MEA, polysorbate 60, polysorbate 80, isosteareth-20, PEG-60 almond glyceride, and PEG-20 methyl glucose sesquisse. The method according to any one of Embodiments 1 to 15, wherein the emulsifier is selected from the group consisting of theate, PEG-7 glyceryl cocoate, PEG-8 stearate, PEG-8 caprate, PEG-35 almond glyceride, PEG-6 laurate, laureth-7, steareth-10, isotrideceth-8, PEG-35 castor oil, isotrideceth-9, PEG-40 castor oil, ceteareth-12, laureth-9, PEG-40 hydrogenated castor oil, PEG-20 glyceryl isostearate, PEG-20 stearate, and mixtures thereof, or comprises the same.

[0030] Embodiment 17: The method according to any one of Embodiments 1 to 15, wherein the emulsifier comprises one or more emulsifiers, a first emulsifier having an HLB value of about 1 to about 9, and a second emulsifier having an HLB value of about 10 to about 20.

[0031] Embodiment 18: The first emulsifier is glycol distearate, sorbitan trioleate, sorbitan tristearate, sorbitan triisostearate, glyceryl isostearate, propylene glycol isostearate, glycol stearate, sorbitan sesquioleate, glyceryl stearate, lecithin, sorbitan oleate, sorbitan monostearate, sorbitan stearate, sorbitan isostearate, steareth-2, oleth-2, PEG- The method according to Embodiment 17, selected from the group consisting of 7 hydrogenated castor oil, laureth-2, sorbitan palmitate, laureth-3, glyceryl laurate, ceteth-2, PEG-30 dipolyhydroxystearate, glyceryl stearate SE, sorbitan stearate (and) sucrose cocoate, PEG-4 dilaurate, methyl glucose sesquistearate, PEG-8 dioleate, sorbitan laurate, PEG-40 sorbitan perolate, and mixtures thereof.

[0032] Embodiment 19: The second emulsifier is laureth-4, PEG-7 glyceryl cocoate, PEG-20 almond glyceride, PEG-25 hydrogenated castor oil, stearamide MEA, glyceryl stearate (and) PEG-100 stearate, polysorbate 81, polysorbate 85, polysorbate 65, PEG-7 glyceryl cocoate, PEG-8 stearate, PEG-8 caprate, PEG-35 almond glyceride, PEG-6 laureth Laureth-7, Steareth-10, Isotrideceth-8, PEG-35 Castor Oil, Isotrideceth-9, PEG-40 Castor Oil, Ceteareth-12, Laureth-9, PEG-40 Hydrogenated Castor Oil, PEG-20 Glyceryl Isostearate, PEG-20 Stearate, PEG-40 Sorbitan Perisostearate, PEG-7 Oliveate, Cetearyl Glucoside, PEG-8 Oleate, Polyglyceryl-3 Methyl Glucose Distearate, Oleate Su-10, Oleth-10 / Polyoxyl 10 Oleyl Ether NF, Ceteth-10, PEG-8 Laurate, Cocamide MEA, Polysorbate 60, Polysorbate 80, Isosteareth-20, PEG-60 Almond Glyceride, PEG-20 Methyl Glucose Sesquistearate, Ceteareth-20, Oleth-20, Steareth-20, Steareth-21, Ceteth-20, Isoceth-20, Polysorbate 20, Polysorbate 40, Ceteareth The method according to Embodiment 17 or 18, selected from the group consisting of -25, ceteareth-30, PEG-30 stearate, laureth-23, PEG-75 lanolin, polysorbate 20, PEG-40 stearate, PEG-100 stearate, steareth-100, PEG-80 sorbitan laurate, polyoxyethylene stearate (e.g., polyoxyethylene (40) stearate), polyoxyethylene ether, and mixtures thereof.

[0033] Embodiment 20: The method according to any one of Embodiments 1 to 19, wherein 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), cannabiclomevalin (CBCV), cannabigerovalin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerol acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabivaric acid (THCV A), and mixtures thereof.

[0034] Embodiment 21: The method according to any one of Embodiments 1 to 20, wherein the cannabinoid comprises cannabidiol.

[0035] Embodiment 22: A nanoemulsion comprising at least one cannabinoid, wherein the nanoemulsion is obtained or can be obtained by a method comprising the steps of (a) providing an oil phase containing at least one cannabinoid, (b) providing an aqueous phase, (c) combining the oil phase and the aqueous phase to form a macroemulsion, and (d) processing the macroemulsion to form a nanoemulsion, wherein at least one of the oil phase and the aqueous phase comprises one or more emulsifiers.

[0036] Embodiment 23: The nanoemulsion according to Embodiment 22, wherein the zeta potential of the nanoemulsion is less than approximately -10 mV.

[0037] Embodiment 24: The nanoemulsion according to Embodiment 22 or 23, wherein the nanoemulsion comprises droplets of an oil phase dispersed in an aqueous phase, and the droplets have an average diameter of about 1 nm to about 200 nm.

[0038] Embodiment 25: A nanoemulsion comprising (a) an oil phase containing at least one cannabinoid, and (b) an aqueous phase, wherein at least one of the oil phase and the aqueous phase contains one or more emulsifiers, and the zeta potential of the nanoemulsion is less than about -10 mV.

[0039] Embodiment 26: An oral product comprising a nanoemulsion containing at least one cannabinoid, wherein the nanoemulsion is (a) obtained or can be obtained by the method defined in any one of Embodiments 1 to 21, or (b) as defined in any one of Embodiments 22 to 25.

[0040] Embodiment 27: The oral product according to Embodiment 26, further comprising a filler.

[0041] Embodiment 28: The oral product according to claim 26 or 27, wherein the water activity of the oral product is about 0.85 or less.

[0042] Embodiment 29: A pouch-packaged oral product comprising a saliva-permeable pouch and an oral product defined in any one of Embodiments 26 to 28 incorporated within the pouch.

[0043] Embodiment 30: A package containing an oral product as defined in any one of Embodiments 26 to 28 or at least one pouch-packaged oral product as defined in Embodiment 29.

[0044] Embodiment 31: The method according to any one of Embodiments 1 to 30, a nanoemulsion, product, or package, wherein the cannabinoid is replaced whole or partially with a cannabimimeric.

[0045] The above and other features, aspects, and advantages of this disclosure will become apparent upon reading the following detailed description, which is briefly described below. The present invention includes any combination of two, three, four or more of the above embodiments, and any combination of any two, three, four or more features or elements described herein, whether or not such features or elements are explicitly combined in the description of a particular embodiment herein. This disclosure is intended to be read holistically, and unless otherwise indicated as is clear from the context, any separable features or elements of the disclosed invention should be interpreted as being combinable as intended in any of its various aspects and embodiments.

[0046] Since the aspects of this disclosure have been described above using the general terminology mentioned above, the following will refer to the accompanying drawings, although these drawings are not necessarily drawn to a specific scale. The drawings are for illustrative purposes only and should not be construed as limiting the disclosure. Next, embodiments of the present invention will be described as examples, with reference to the accompanying drawings. [Brief explanation of the drawing]

[0047] [Figure 1] This is a cross-sectional view of an embodiment of a pouch-packaged product, showing the entire width of the product and the outer pouch filled with the composition of the present disclosure. [Modes for carrying out the invention]

[0048] A method for preparing a nanoemulsion containing at least one cannabinoid, as described herein, (a) A step of providing an oil phase containing at least one cannabinoid, (b) A step of providing an aqueous phase, (c) A process of combining the oil phase and the aqueous phase to form a macroemulsion, (d) Process to form nanoemulsions by processing macroemulsions. Includes, At least one of the oil phase and the aqueous phase contains one or more emulsifiers. A method is provided.

[0049] The following provides a more complete description of the Disclosure, with illustrative embodiments. These exemplary embodiments are provided so that the Disclosure may be thorough and complete and so that the scope of the Disclosure may be fully conveyed to those skilled in the art. In practice, the Disclosure may be implemented in many different forms and should not be construed as being limited to the embodiments described herein, but rather these embodiments are provided so as to satisfy the applicable legal requirements of the Disclosure. As used herein and in the claims, the singular forms “a,” “an,” and “the” refer to multiple subjects unless otherwise indicated by context. References to “dry weight percent” or “dry weight basis” refer to the weight of the dry components (i.e., all components excluding water). References to “wet weight” refer to the weight of the composition including water. Unless otherwise indicated, references to “weight percent” of a composition reflect the total wet weight of the composition (i.e., including water).

[0050] The methods and products described herein include the step of forming a nanoemulsion comprising an aqueous phase and an oil phase, the nanoemulsion comprising at least one cannabinoid. The relative amounts of the various components in the methods and products may vary, but are typically selected to impart desired sensory and performance characteristics to the nanoemulsion or oral product containing the nanoemulsion. Examples of individual components of the product are described below.

[0051] method According to some embodiments described herein, a method for preparing a nanoemulsion containing at least one cannabinoid, (a) A step of providing an oil phase containing at least one cannabinoid, (b) A step of providing an aqueous phase, (c) A process of combining the oil phase and the aqueous phase to form a macroemulsion, (d) Process to form nanoemulsions by processing macroemulsions. Includes, At least one of the oil phase and the aqueous phase contains one or more emulsifiers. A method is provided.

[0052] (a) As described herein, (a) includes the step of providing an oil phase. The oil phase contains an oil combined with at least one cannabinoid. Any suitable oil, including petroleum-based oils (e.g., mineral oil) and natural or naturally derived oils (e.g., oils derived from plant materials or animal sources), may be used as the oil phase in (a). In some embodiments, the oil contains mineral oil. In some embodiments, the oil contains long-chain fatty acids, monoacylglycerols, diacylglycerols, triacylglycerols, or combinations thereof, where the acyl group is a long-chain fatty acid. As used herein, “long-chain fatty acid” refers to a carboxylic acid (CO2H) having an aliphatic carbon chain of about 11 to about 21 carbon atoms. The aliphatic carbon chain may be linear or branched. The aliphatic carbon chain may be saturated (i.e., all sp 3 It may be carbon-carbon (having carbon atoms) or unsaturated (i.e., having at least one unsaturated site). As used herein, the term “unsaturated” means carbon-carbon, sp at one or more positions in an aliphatic carbon chain. 2 This refers to the presence of a double bond. Unsaturated alkyl groups can be monounsaturated or polyunsaturated. Typical long-chain fatty acids include, but are not limited to, undecylic acid, undecanoic acid, lauric acid, tridecanoic acid, myristic acid, pentadecanoic acid, palmitic acid, margaric acid, stearic acid, nonadecanoic acid, arachidic acid, heneicosanoic acid, alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid, cervonic acid, linoleic acid, linolelideic acid, gamma-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid.

[0053] In some embodiments, the oil comprises acylglycerols, such as monoacylglycerols, diacylglycerols, or triacylglycerols, where the acyl group is a long-chain fatty acid as described herein. In some embodiments, the oil comprises triacylglycerols, where the acyl group is a long-chain fatty acid as described herein. In some embodiments, the oil comprises polyunsaturated long-chain fatty acids, or mono, di, or triacylglycerols containing polyunsaturated long-chain fatty acids as acyl components. The chain length of fatty acids in naturally occurring triglycerides varies, but is typically 16, 18, or 20 carbon atoms. In some embodiments, the concentration of polyunsaturated fatty acids in the oil (as free fatty acids, or, for example, as triglycerides) may range from about 2% to 100% (weight / weight), for example, about 5% to 100% (weight / weight), or greater than 10%, for example, 20% to 80% (weight / weight).

[0054] In some embodiments, the oil may consist mainly of long-chain triacylglycerols (LCTs). In some embodiments, the oil may include medium-chain triacylglycerols (MCTs) and / or short-chain triacylglycerols (SCTs). In some embodiments, the oil may include castor oil, corn oil, coconut oil, cod liver oil, evening primrose oil, cottonseed oil, palm oil, rice bran oil, sesame oil, rapeseed oil, canola oil, cocoa butter, linseed oil, olive oil, peanut oil, soybean oil, safflower oil, sunflower oil, olive oil, or a combination thereof.

[0055] The amount of oil present in the final nanoemulsion can vary. In some embodiments, (a) includes a step of providing oil such that the final nanoemulsion contains oil in an amount of about 1% to about 80% by weight, for example about 5% to about 60% by weight, about 5% to about 50% by weight, for example about 5% to about 30% by weight, for example about 10% to about 20% by weight, based on the total weight of the emulsion.

[0056] As described herein, (a) includes the step of providing an oil phase containing at least one cannabinoid. Cannabinoids are certain types of natural or synthetic compounds that act on intracellular cannabinoid receptors (i.e., CB1 and CB2) that inhibit the release of neurotransmitters in the brain. Cannabinoids are cyclic molecules that exhibit certain properties, such as the ability to easily cross the blood-brain barrier. Cannabinoids can be naturally occurring from plants such as cannabis (phytocannabinoids), derived from animals (endocannabinoids), or artificially produced (synthetic cannabinoids). Cannabis species represent at least 85 different phytocannabinoids, including cannabigerol, cannabichromene, cannabidiol, tetrahydrocannabinol, cannabinol and cannabinodiol, as well as other cannabinoids such as cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN) and cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabiclomevalin (CBCV), cannabigerovalin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerol acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabitriol (CBO), and tetrahydrocannabinolic acid (tetrahydrocannabmolic acid). It can be classified into subclasses including THCA (then acid) and tetrahydrocannabivaric acid (THCV A).

[0057] 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), cannabiclomevalin (CBCV), cannabigerovalin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerol acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivaric acid (THCV A), and mixtures thereof. In some embodiments, the cannabinoid includes at least tetrahydrocannabinol (THC). In some embodiments, the cannabinoid is tetrahydrocannabinol (THC). In some embodiments, the cannabinoid comprises at least cannabidiol (CBD).

[0058] In some embodiments, the cannabinoid is cannabidiol (CBD) or a pharmaceutically acceptable salt thereof. In some embodiments, the cannabidiol is synthetic cannabidiol. In some embodiments, the cannabinoid is added to the emulsion in the form of an isolate. In some embodiments, the cannabidiol is added to the emulsion in the form of an isolate. The isolate is an extract from a plant such as cannabis, where the active substance of interest (in this case, a cannabinoid such as CBD) is present in high purity, for example, over 95%, over 96%, over 97%, over 98%, or over 99%.

[0059] In some embodiments, the cannabinoid is a high-purity CBD isolate, and the amount of any other cannabinoid in the nanoemulsion is less than or equal to about 1% by weight of the nanoemulsion, for example less than or equal to about 0.5% by weight of the nanoemulsion, for example less than or equal to about 0.1% by weight of the nanoemulsion, for example less than or equal to about 0.01% by weight of the nanoemulsion.

[0060] The selection of cannabinoids that may be present in the disclosed emulsion and their specific percentages may vary depending on the desired flavor, texture, and other characteristics of the emulsion and any product into which the emulsion is incorporated.

[0061] Alternatively, or in addition to cannabinoids, oral products may contain cannabimimetics. Cannabimimetics are a class of compounds derived from plants other than cannabis that have biological effects on the endocannabinoid system similar to those of cannabinoids. Examples include yangonin, α-amyrin or β-amyrin (also classified as terpenes), cyanidin, curcumin (turmeric), catechin, quercetin, salvinorin A, N-acylethanolamine, and N-alkylamide lipids. Such compounds may be used in the same amounts and proportions as those described herein for cannabinoids.

[0062] In some embodiments, (a) includes the step of bringing an oil into contact with at least one cannabinoid in order to provide an oil phase containing at least one cannabinoid.

[0063] In some embodiments, (a) includes the step of mixing the oil with at least one cannabinoid. This mixing can further utilize high shear mixing, high pressure, high temperature, etc. In some embodiments, (a) includes the step of heating the oil phase to a temperature of about 50°C to dissolve at least one cannabinoid in the oil phase. For example, the oil phase may be heated to a temperature of about 50°C to about 90°C, for example, about 55°C to about 85°C, for example, about 60°C to about 85°C, for example, about 65°C to about 85°C, for example, about 70°C to about 85°C.

[0064] Therefore, in some embodiments, the method further includes (a)(1) heating the oil phase to a temperature of at least about 50°C (e.g., about 60°C to about 85°C) to dissolve at least one cannabinoid in the oil phase.

[0065] In some embodiments, (a) includes the step of mixing the oil with at least one cannabinoid for a period of time of about 1 minute to about 60 minutes, for example, about 5 minutes to about 45 minutes, for example, about 10 minutes to about 30 minutes, for example, about 15 minutes to about 20 minutes (at a temperature of, for example, at least about 50°C). In some embodiments, (a) includes the step of mixing the oil with at least one cannabinoid for at least about 10 minutes (at a temperature of, for example, at least about 50°C).

[0066] In some embodiments, (a) comprises providing an oil phase, the weight ratio of cannabinoids to oil in the oil phase being any preferred ratio for dispersing (or dissolving) the cannabinoids in the oil while yielding an effective amount of cannabinoids. In some embodiments, the weight ratio of cannabinoids to oil is about 2:1 to about 1:20, for example about 1:1 to about 1:10, for example about 1:1 to about 1:5, for example about 1:2.

[0067] In some embodiments, the weight ratio of oil to at least one cannabinoid is about 1:1 to about 10:1, for example, about 1:1 to about 5:1. As described herein, “weight ratio of oil to at least one cannabinoid” refers to the weight ratio of oil to cannabinoids in the oil phase.

[0068] (b) As described herein, (b) includes the step of providing an aqueous phase (or “aqueous phase”). The aqueous phase comprises at least water.

[0069] The aqueous phase may also optionally contain one or more additives, such as preservatives, humectants, emulsifiers, flavoring agents, etc.

[0070] Water may be present, for example, as purified water or ultrapure water, physiological saline, buffered physiological saline, or a buffered aqueous phase. In some embodiments, further hydrophilic water-soluble components may be added to the water, including short-chain monovalent, divalent, and polyvalent alcohols (e.g., ethanol, benzyl alcohol, glycerol, propylene glycol, propylene carbonate, polyethylene glycol with an average molecular weight of about 200 to about 10,000, diethylene glycol monoethyl ether, and combinations thereof).

[0071] The water content of the final emulsion can vary depending on the desired properties. In some embodiments, (b) includes a step of providing water in an amount such that the final water content of the nanoemulsion is about 10% by weight to about 90% by weight, based on the total weight of the emulsion. In some embodiments, the water content is about 15% by weight to about 60% by weight, for example, about 20% by weight to about 50% by weight, for example, about 25% by weight to about 40% by weight, based on the total weight of the emulsion.

[0072] The aqueous phase may contain one or more water-soluble or water-dispersible additives. Therefore, in some embodiments, (b) further includes the step of bringing water into contact with one or more additives to produce the aqueous phase.

[0073] In some embodiments, the method further includes the step of (b)(1) combining water with one or more emulsifiers. Thus, the aqueous phase may include water combined with one or more emulsifiers.

[0074] The following sections describe including one or more emulsifiers in the aqueous phase, but please note that such emulsifiers may also be included in the oil phase. Therefore, one or more emulsifiers may be included in the oil phase, the aqueous phase, and / or both the oil and aqueous phases.

[0075] "Emulsifier" means a substance that helps form and stabilize an emulsion by promoting the dispersion of hydrophobic and hydrophilic components (e.g., oil and water). Generally, emulsifiers are amphiphilic molecules selected from, for example, nonionic and ionic amphiphilic molecules. The expression "amphiphilic molecule" means any molecule with a bipolar structure that includes at least one hydrophobic part and at least one hydrophilic part and has the property of reducing the surface tension of water and the interfacial tension between the water and oil phases. The emulsifiers / amphiphilic molecules provided herein are also called, for example, surfactants and emulsifiers.

[0076] In some embodiments, the emulsifier is selected from the group consisting of small molecule surfactants, phospholipids, proteins, polysaccharides, and mixtures thereof.

[0077] In some embodiments, one or more emulsifiers are selected from the group consisting of fatty acid polyethylene glycol esters, fatty acid propylene glycol esters, polysorbates, fatty acid polyglycerol esters, polyglycerol polyricinoleate, fatty acid sorbitan esters, fatty acid sucrose esters, lecithin, enzyme-treated lecithin, glycerin fatty acid esters, monoglyceride acetate esters, monoglyceride lactate esters, monoglyceride citrate esters, monoglyceride succinate esters, monoglyceride diacetyl tartrate esters, calcium stearoyl dilactate, chitin and chitosan derivatives, natural and modified starches, natural and modified hydrocolloids, natural and modified polysaccharides, natural and modified cellulose, natural and modified proteins, synthetic amphiphilic polymers, and mixtures thereof.

[0078] In some embodiments, one or more emulsifiers are selected from the group consisting of fatty acid polyethylene glycol esters, fatty acid propylene glycol esters, polysorbate, fatty acid polyglycerol esters, polyglycerol polyricinoleate, fatty acid sorbitan esters, fatty acid sucrose esters, lecithin, glycerin fatty acid esters, monoglyceride acetate esters, monoglyceride lactate esters, monoglyceride citrate esters, monoglyceride succinate esters, monoglyceride diacetyl tartrate esters, calcium stearoyl dilactate, and mixtures thereof.

[0079] In some embodiments, one or more emulsifiers are selected from the group consisting of polyethylene glycol esters of fatty acids, polyethylene glycol esters of lecithin, and mixtures thereof.

[0080] In some embodiments, one or more emulsifiers include glycol distearate, sorbitan trioleate, sorbitan tristearate, sorbitan triisostearate, glyceryl isostearate, propylene glycol isostearate, glycol stearate, sorbitan sesquioleate, glyceryl stearate, lecithin, sorbitan oleate, sorbitan monostearate, sorbitan stearate, sorbitan isostearate, steareth-2, oleth-2, PEG-7 hydrogenated castor oil, laureth-2, and sorbitan palmitate. Tan, Laureth-3, Glyceryl Laurate, Ceteth-2, PEG-30 Dipolyhydroxystearate, Glyceryl Stearate SE, Sorbitan Stearate (and) Sucrose Cocoate, PEG-4 Dilaurate, Methyl Glucose Sesquistearate, PEG-8 Dioleate, Sorbitan Laurate, PEG-40 Sorbitan Perolate, Laureth-4, PEG-7 Glyceryl Cocoate, PEG-20 Almond Glyceride, PEG-25 Hydrogenated Castor Oil, Stearamide MEA, Glyceryl Stearate (and) PEG-100 Stearate Polysorbate 81, Polysorbate 85, Polysorbate 65, PEG-7 Glyceryl Cocoate, PEG-8 Stearate, PEG-8 Caprate, PEG-35 Almond Glyceride, PEG-6 Laurate, Laureth-7, Steareth-10, Isotrideceth-8, PEG-35 Castor Oil, Isotrideceth-9, PEG-40 Castor Oil, Ceteareth-12, Laureth-9, PEG-40 Hydrogenated Castor Oil, PEG-20 Glyceryl Isostearate, PEG-20 Stearate, PEG-40 Sorbitan Perisostearate, PEG-7 Olive Oil Cetearyl glucoside, PEG-8 oleate, polyglyceryl-3 methyl glucose distearate, oleth-10, oleth-10 / polyoxyl-10 oleyl ether NF, ceteth-10, PEG-8 laurate, cocamide MEA, polysorbate 60, polysorbate 80, isosteareth-20, PEG-60 almond glyceride, PEG-20 methyl glucose sesquistearate, ceteareth-20, oleth-20, steareth-20, steareth-21, ceteth-20, isoceth-20, polysorbate 20, polysorbate 40,Selected from the group consisting of ceteareth-25, ceteareth-30, PEG-30 stearate, laureth-23, PEG-75 lanolin, polysorbate 20, PEG-40 stearate, PEG-100 stearate, steareth-100, PEG-80 sorbitan laurate, polyoxyethylene stearate (e.g., polyoxyethylene (40) stearate), polyoxyethylene ether, and mixtures thereof.

[0081] In some embodiments, one or more emulsifiers have an overall HLB value in the range of about 10 to about 15, for example, about 11 to about 15, for example, about 11 to about 14, for example, about 11 to about 13.5. As will be understood by those skilled in the art, HLB is the hydrophilic-lipophilic balance of an emulsifier or surfactant, and is a measure of the degree to which it is hydrophilic or lipophilic. HLB values ​​can be determined by calculating values ​​in various regions of a molecule, as described in Griffin in Griffin, William C. (1949), "Classification of Surface-Active Agents by 'HLB'" (PDF), Journal of the Society of Cosmetic Chemists, Vol. 1 (No. 5): pp. 311-326; Griffin, William C. (1954), "Calculation of HLB Values ​​of Non-Ionic Surfactants" (PDF), Journal of the Society of Cosmetic Chemists, Vol. 5 (No. 4): pp. 249-256; and Davies in Davies JT (1957), "A quantitative kinetic theory of emulsion type, I. Physical chemistry of the emulsifying agent" (PDF), Gas / Liquid and Liquid / Liquid Interface, Proceedings of the International Congress of Surface Activity, pp. 426-438. HLB values ​​can be determined according to the industry standard textbook, namely "The HLB SYSTEM, a time-saving guide to emulsifier selection," ICI Americas Inc., first edition 1976, revised March 1980. The HLB values ​​of the emulsifiers described herein were determined according to this standard method.

[0082] In some embodiments, one or more emulsifiers have an HLB value of about 11 to about 15. In some embodiments, one or more emulsifiers have an HLB value of about 11 to about 13.5. In some embodiments, the overall HLB value of one or more emulsifiers present in the nanoemulsion is about 11 to about 15, for example, about 11 to about 13.5.

[0083] In some embodiments, the nanoemulsion comprises an emulsifier having an HLB value of about 11 to about 15, the emulsifier being stearamide MEA, glyceryl stearate (and) PEG-100 stearate, polysorbate 85, PEG-7 olivet, cetearyl glucoside, PEG-8 oleate, polyglyceryl-3 methyl glucose distearate, oleth-10, oleth-10 / polyoxyl-10 oleyl ether NF, ceteth-10, PEG-8 laurate, cocamide MEA, polysorbate 60, polysorbate 80, isosteareth-20, The following are selected from the group consisting of PEG-60 almond glyceride, PEG-20 methyl glucose sesquistearate, PEG-7 glyceryl cocoate, PEG-8 stearate, PEG-8 caprate, PEG-35 almond glyceride, PEG-6 laurate, laureth-7, steareth-10, isotrideceth-8, PEG-35 castor oil, isotrideceth-9, PEG-40 castor oil, ceteareth-12, laureth-9, PEG-40 hydrogenated castor oil, PEG-20 glyceryl isostearate, PEG-20 stearate, and mixtures thereof.

[0084] In some embodiments, the nanoemulsion comprises at least two emulsifiers having different HLB values. In some embodiments, the nanoemulsion comprises a first emulsifier having a low HLB value and a second emulsifier having a high HLB value. In some embodiments, the nanoemulsion comprises a first emulsifier having an HLB value of about 1 to about 9 (e.g., about 2 to 9, e.g., about 3 to 9, e.g., about 3 to 8) and a second emulsifier having an HLB value of about 10 to about 20 (e.g., about 10 to 18, e.g., about 11 to 17). In some embodiments, the overall (i.e., combined) HLB value of the first and second emulsifiers is about 11 to about 15, e.g., about 11 to about 13.5.

[0085] A first emulsifier having an HLB value of about 1 to about 9 may be selected from any suitable emulsifier having such an HLB value. For example, the first emulsifier may be an emulsifier having an HLB value of about 1 to about 9, selected from monoglycerides and diglycerides of fatty acids including glyceryl stearate and glyceryl oleate; fatty acid esters of C12-C22 fatty alcohols including fatty acid esters of cetyl alcohol and fatty acid esters of stearoyl alcohol; mixtures of fatty acid esters of cetyl alcohol and fatty acid esters of stearoyl alcohol; mixtures of fatty acid esters of cetyl alcohol and fatty acid esters of stearoyl alcohol in which the fatty acid is derived from olive oil (e.g., cetearyl olivine); fatty acid esters of sorbitol including sorbitan oleate; fatty acid esters of sorbitol (sorbitan olivine or cetearyl olivine) in which the fatty acid is derived from olive oil; and mixtures thereof.

[0086] In some embodiments, the first emulsifier is an emulsifier having an HLB value of about 1 to about 9, selected from fatty acid monoglycerides and diglycerides, fatty acid esters of C12-C22 fatty alcohols, fatty acid esters of sorbitol, and mixtures thereof. In some embodiments, the first emulsifier is glycol distearate, sorbitan trioleate, sorbitan tristearate, sorbitan triisostearate, glyceryl isostearate, propylene glycol isostearate, glycol stearate, sorbitan sesquioleate, glyceryl stearate, lecithin (e.g., soy lecithin), sorbitan oleate, sorbitan monostearate, sorbitan stearate, sorbitan isostearate, s Selected from the group consisting of theareth-2, oleth-2, PEG-7 hydrogenated castor oil, laureth-2, sorbitan palmitate, laureth-3, glyceryl laurate, ceteth-2, PEG-30 dipolyhydroxystearate, glyceryl stearate SE, sorbitan stearate (and) sucrose cocoate, PEG-4 dilaurate, methyl glucose sesquistearate, PEG-8 dioleate, sorbitan laurate, PEG-40 sorbitan perolate, and mixtures thereof.

[0087] In some embodiments, the first emulsifier is lecithin or comprises lecithin. In some embodiments, the first emulsifier is soy lecithin or comprises soy lecithin.

[0088] The second emulsifier can be selected from any suitable emulsifier having an HLB value of about 10 to about 20. In some embodiments, the second emulsifier is an emulsifier having an HLB value of 10 to 20, selected from fatty acid esters of polyethylene glycol, for example, fatty acid esters of polyethylene glycol in which the fatty acid is derived from coconut oil (including PEG7), fatty acid esters of polyglycerol, for example, fatty acid esters of polyglycerol and oleic acid (for example, polyglyceryl 10 oleate), and mixtures thereof.In some embodiments, the second emulsifier is laureth-4, PEG-7 glyceryl cocoate, PEG-20 almond glyceride, PEG-25 hydrogenated castor oil, stearamide MEA, glyceryl stearate (and) PEG-100 stearate, polysorbate 81, polysorbate 85, polysorbate 65, PEG-7 glyceryl cocoate, PEG-8 stearate, PEG-8 caprate, PEG-35 almond glyceride, PEG-6 laurate, laureth-7, steareth-10, isotrideceth-8, PEG-35 castor oil, isotrideceth-9, PEG-40 castor oil, ceteareth-12, laureth-9, PEG-40 hydrogenated castor oil, PEG-20 glyceryl isostearate, PEG-20 stearate, PEG-40 sorbitan perisostearate, PEG-7 olive, cetearyl glucoside, PEG-8 oleate, polyglyceryl-3 methyl glucoside Distetearate, Oleth-10, Oleth-10 / Polyoxyl 10 Oleyl Ether NF, Ceteth-10, PEG-8 Laurate, Cocamide MEA, Polysorbate 60, Polysorbate 80, Isosteareth-20, PEG-60 Almond Glyceride, PEG-20 Methyl Glucose Sesquistearate, Ceteareth-20, Oleth-20, Steareth-20, Steareth-21, Ceteth-20, Isoceth-20, Polysorbate 20, Poly The following may be selected: sorbate 40, ceteareth-25, ceteareth-30, PEG-30 stearate, laureth-23, PEG-75 lanolin, polysorbate 20, PEG-40 stearate, PEG-100 stearate, steareth-100, PEG-80 sorbitan laurate, polyoxyethylene stearate (e.g., polyoxyethylene (40) stearate), polyoxyethylene ether, and mixtures thereof.

[0089] In some embodiments, the second emulsifier is or comprises polyoxyethylene stearate (e.g., polyoxyethylene (40) stearate).

[0090] In some embodiments, the emulsifier is a combination of lecithin (e.g., soy lecithin) and polyoxyethylene stearate (e.g., polyoxyethylene (40) stearate), or comprises these two.

[0091] In some embodiments, one or more emulsifiers include neutral, positively charged, or negatively charged, natural or synthetic phospholipid molecules. The phospholipid consists of two fatty acid tails and a phosphate group head, which are connected via a third molecule, glycerol. Non-limiting examples of natural phospholipids include lecithin (e.g., soy lecithin and / or egg lecithin), phosphatidylcholine-enriched lecithin, phosphatidylserine-enriched lecithin, enzyme-modified lecithin, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidic acid, sphingomyelin, diphosphatidylglycerol, phosphatidylserine, phosphatidylcholine and cardiolipin; synthetic phospholipids, e.g., dimyristoylphosphatidylcholine, dimyristoylphosphatidylglycerol, distearoylphosphatidylglycerol and dipalmitoylphosphatidylcholine; and hydrogenated or partially hydrogenated lecithin and phospholipids. Non-exclusive examples of synthetic phospholipid derivatives include phosphatidic acid (DMPA, DPPA, DSPA), phosphatidylcholine (DDPC, DLPC, DMPC, DPPC, DSPC, DOPC, POPC, DEPC), phosphatidylglycerol (DMPG, DPPG, DSPG, POPG), phosphatidylethanolamine (DMPE, DPPE, DSPE, DOPE), phosphatidylserine (DOPS), and PEG phospholipids (mPEG-phospholipids, polyglycerol-phospholipids, functionalized phospholipids, and terminally activated phospholipids).

[0092] In some embodiments, the emulsifier comprises a surfactant, which may be ionic (anionic or cationic), zwitterionic or nonionic, and may be hydrophobic or hydrophilic. Examples of hydrophobic surfactants include, but are not limited to, Maisine 35-1, Imwitor 742, Capmul MCM, Capmul PG 12, Lauroglycol 90, Lauroglycol FCC, Caproyl 90, Captex 250, and fatty acids selected from the group consisting of octanoic acid, decanoic acid, undecanoic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid. As used herein, hydrophobic surfactants may also be called poorly water-soluble surfactants or lipophilic surfactants.

[0093] Examples of hydrophilic surfactants may include, but are not limited to, polyoxyethylene sorbitan fatty acid esters, hydrogenated castor oil ethoxylates, PEG monoesters and diesters of palmitic acid and stearic acid, fatty acid ethoxylates, and combinations thereof.

[0094] Examples of suitable surfactants generally include, but are not limited to, polyoxyethylene sorbitan fatty acid esters; for example, monolauryl and trilauryl, palmityl, stearyl and oleyl esters; for example, products of the type known as polysorbate and marketed under the trade name Tween®; polyoxyethylene fatty acid esters, for example, polyoxyethylene stearates of the type known under the trade name Myrj® and marketed; polyoxyethylene ethers, for example, those available under the trade name Brij®; and polyoxyethylene castor oil derivatives, for example, products of the type known as Cremophors® and marketed.Particularly suitable are polyoxyl 35 castor oil (Cremophor® EL) and polyoxyl 40 hydrogenated castor oil (Cremophor® RH40); α-tocopherol, α-tocopheryl polyethylene glycol succinate (vitamin E TPGS), α-tocopherol palmitate and α-tocopherol acetate; PEG glyceryl fatty acid esters, such as PEG-8 glyceryl caprylate / caprate (commercially known as Labrasol®), PEG-4 glyceryl caprylate / caprate (Labrafac Hydro WL 1219), PEG-32 glyceryl laurate (Gelucire 44 / 14), PEG-6 glyceryl monooleate (Labrafil® M1944 CS), and PEG-6 glyceryl linoleate (Labrafil® M2125). CS); propylene glycol mono-fatty acid and di-fatty acid esters, e.g., propylene glycol laurate, propylene glycol caprylate / caprate; further, diethylene glycol monoethyl ether (DGME), commercially known as Transcutol® (Gattefosse, Westwood, NJ); fatty acid esters, e.g., commercially available types known by the name Span® (e.g., Span 85); polyoxyethylene-polyoxypropylene copolymers, e.g., commercially available products known as Pluronic® or Poloxamer®; glycerol triacetates; and monoglycerides and acetylated monoglycerides, e.g., glycerol monodicocoate (Imwitor® 928), glycerol monocaprylate (Imwitor® 308), and mono and diacetylated monoglycerides.

[0095] In some embodiments, the emulsifier is a surfactant, a phospholipid, an amphiphilic polysaccharide, an amphiphilic protein, or a combination thereof. In some embodiments, one or more emulsifiers are ionic, zwitterionic, or nonionic surfactants. In some embodiments, one or more emulsifiers include Tween 20, Tween 80, Span 20, Span 40, Span 60, Span 80, lecithin, Myij 52, Brij 35, Brij 97, hydrophilic colloidal gum, modified starch, or a combination thereof.

[0096] In some embodiments, one or more emulsifiers include a combination of lecithin and Myrj 52.

[0097] The concentrations of one or more emulsifiers present in the final nanoemulsion can vary. In some embodiments, (b)(1) includes a step of combining water with one or more emulsifiers in an amount such that the total final concentration of emulsifiers in the nanoemulsion may be up to about 30% by weight, for example, about 0.1% to about 25% by weight, about 5% to about 25% by weight, or about 10% to about 25% by weight, based on the entire emulsion. In some embodiments, the resulting nanoemulsion contains a combination of lecithin and Myrj52 in an amount of about 0.1% to about 25% by weight, about 5% to about 25% by weight, or about 10% to about 25% by weight, based on the entire emulsion.

[0098] In some embodiments, (b)(1) includes the step of combining water with one or more emulsifiers in an amount such that the total final concentration of emulsifiers in the nanoemulsion is about 0.1% to about 20% by weight of the oral product containing the nanoemulsion, for example, about 1% to about 15% by weight of the oral product, for example, about 2.5% to about 10% by weight of the oral product, for example, about 5% to about 10% by weight of the oral product. In some embodiments, (b)(1) includes the step of combining water with a combination of lecithin and Myrj52 such that the total final concentration of emulsifiers in the nanoemulsion is about 0.1% to about 20% by weight of the nanoemulsion, for example, about 1% to about 15% by weight of the nanoemulsion, for example, about 2.5% to about 10% by weight of the nanoemulsion, for example, about 5% to about 10% by weight of the nanoemulsion.

[0099] In some embodiments, (b)(1) includes the step of combining water with one or more emulsifiers by high-shear mixing. In some embodiments, the high-shear mixing is carried out for a sufficient period of time until a homogeneous mixture is formed. In some embodiments, the high-shear mixing is carried out for a period of at least about 10 minutes, for example, about 10 minutes to about 60 minutes, for example, about 15 minutes to about 45 minutes, for example, about 20 minutes to about 30 minutes.

[0100] (c) As described herein, (c) includes the step of combining the oil phase and the aqueous phase to form a macroemulsion.

[0101] Where used herein, “macroemulsion” refers to an emulsion in which a dispersed phase is distributed (or “dispersed”) within a continuous phase. The oil phase may be a dispersed phase and the aqueous phase may be a continuous phase (i.e., an oil-in-water emulsion). Alternatively, the aqueous phase may be a dispersed phase and the oil phase may be a continuous phase (i.e., a water-in-oil emulsion). Macroemulsions are typically thermodynamically unstable systems with particle or droplet sizes ranging from approximately 5 nm to 200 μm. Typically, such macroemulsions may have particles with an average radius of 100 nm to 100 μm. Macroemulsion is generally considered a term used to describe typical or conventional emulsions that have not undergone any treatment other than mixing a continuous phase and a dispersed phase.

[0102] In some embodiments, the macroemulsion comprises fine particles of a dispersed phase (e.g., an oil phase) in a continuous phase (e.g., an aqueous phase). The fine particles or droplets may have an average size of about 0.1 μm to about 100 μm, for example, about 1 μm to about 10 μm.

[0103] In some embodiments, (c) includes the step of mixing the oil phase and the aqueous phase to provide a macroemulsion. In some embodiments, (c) includes the step of mixing the oil phase and the aqueous phase by high-shear mixing.

[0104] In some embodiments, (c) includes the step of mixing the oil phase and the aqueous phase (for example by high shear mixing) for at least about 10 minutes, for example at least about 15 minutes, for example at least about 20 minutes, for example at least about 30 minutes. In some embodiments, (c) includes the step of mixing the oil phase and the aqueous phase (for example by high shear mixing) for a period of about 10 minutes to about 60 minutes, for example at about 15 minutes to about 45 minutes, for example at about 15 minutes to about 45 minutes, for example at about 20 minutes to about 30 minutes.

[0105] In some embodiments, (c) includes the step of combining the oil phase and the aqueous phase (for example, by mixing, for example by high-shear mixing) at a temperature of about 50°C or less, for example, about 45°C or less, for example, about 40°C or less. In some embodiments, (c) includes the step of combining the oil phase and the aqueous phase (for example, by mixing, for example by high-shear mixing) at a temperature of about 20°C to about 50°C, for example, about 25°C to about 45°C, for example, about 30°C to about 40°C.

[0106] In some embodiments, (c) includes a step of combining the oil phase and the aqueous phase by high-shear mixing at a temperature of about 40°C or less for a period of about 10 to about 60 minutes.

[0107] In some embodiments, (c) is the following step: (i) The first step is to mix the oil phase and the aqueous phase by high-shear mixing for a period of about 1 minute to about 30 minutes, and (ii) A process of further mixing the oil phase and the aqueous phase for a period of approximately 10 to 60 minutes. Includes.

[0108] In some embodiments, the oil phase and the aqueous phase are combined in (c) in a weight ratio of about 10:1 to about 1:20. In some embodiments, the oil-to-aqueous-water ratio in (c) is about 5:1 to about 1:15, for example about 2:1 to about 1:10, for example about 1.1 to about 1:8, for example about 1:2 to about 1:7, for example about 1:3 to about 1:6, for example about 1:4 to about 1:6. In some embodiments, the oil-to-aqueous-water ratio in (c) is about 1:5 to about 1:10.

[0109] (d) As described herein, (d) includes the step of processing the macroemulsion to form a nanoemulsion.

[0110] Where used herein, “nanoemulsion” is a colloidal particulate system having fine particles in the submicron size range. The particulate matter (also referred herein as droplets or particles) is generally a solid sphere, and the surface of such fine particles is amorphous, negatively charged, and lipophilic. Nanoemulsions generally contain nanoscale particles or droplets with an average size of less than about 1,000 nm. The nanoemulsions described herein include nanoparticles (or nanodroplets) of a dispersed phase emulsified in a continuous phase. In some embodiments, the nanoemulsion includes nanoparticles of an oil phase emulsified in water or an aqueous phase.

[0111] The nanoemulsions described herein generally comprise nanoscale particles (or nanoscale droplets) having an average size (i.e., diameter) of about 10 nm to about 1,000 nm, for example, about 10 nm to about 200 nm, about 20 nm to about 100 nm, or about 40 nm to about 100 nm. In some embodiments, the average particle size is about 100 nm, about 90 nm, about 80 nm, about 70 nm, about 60 nm, about 50 nm, or about 40 nm. In some embodiments, the average particle size is about 40 nm to about 80 nm. In some embodiments, the average particle size is about 40 nm to about 80 nm, and the nanoemulsion is transparent.

[0112] The size of nanoparticles can be determined by quasi-elastic light scattering (QELS), as described in Bloomfield, Ann. Rev. Biophys. Bioeng., Vol. 10, pp. 421–450 (1981), which is incorporated herein by reference. It can also be measured by correlation spectroscopy, which analyzes variations in light scattering due to Brownian motion, or by transmission electron microscopy (TEM).

[0113] Nanoemulsions can be prepared in (d) using high-energy or low-energy methods. High-energy methods utilize mechanical devices (homogenizers) capable of generating strong destructive force that can split the oil and aqueous phases into small oil droplets (see McClements and Rao, Critical Reviews in Food Science and Nutrition, Vol. 51, pp. 285-330 (2011)). Such high-energy methods include the use of high-pressure valve homogenizers, microfluidizers, and sonic treatment methods. Low-energy methods may rely on the spontaneous formation of small oil droplets in the system when the solution or environmental conditions are changed.

[0114] For example, the nanoemulsions disclosed herein may be prepared by mechanical processes that use shear force to break down large emulsion droplets into smaller droplets, such as high-pressure homogenization (including high-pressure heating, microfluidization), high-amplitude sonication, and ultrasonic-assisted emulsification. In some embodiments, nanoemulsions may be formed via the use of high-pressure valve homogenizers, microfluidizers, or ultrasonic homogenizers (including ultrasonic jet homogenizers and ultrasonic probe homogenizers).

[0115] In some embodiments, (d) includes the step of processing the macroemulsion in a homogenizer to form a nanoemulsion. The homogenizer may be selected from a high-pressure valve homogenizer, an ultrasonic jet homogenizer, an ultrasonic probe homogenizer, or a combination thereof.

[0116] In some embodiments, (d) includes the step of sonicating the macroemulsion. The macroemulsion may be sonicated in an ultrasonic jet homogenizer or an ultrasonic probe homogenizer.

[0117] In some embodiments, (d) includes the step of processing the macroemulsion in a microfluidizer to form an emulsion.

[0118] Therefore, the aqueous and oil phases can be combined and homogenized, for example, by a probe sonicator (Sonics and Materials, USA), a high-pressure homogenizer (e.g., manufactured by Gauline or Avestine), or a microfluidizer, to obtain the desired nanoemulsion. The number of passes through the high-pressure homogenizer / microfluidizer can vary depending on the desired particle size for the nanoemulsion. Various methods for producing nanoemulsions containing nano-sized particles within a specific size range are known in the art, for example, using sonication or homogenization. One such method is described in U.S. Patent No. 4,737,323, which is incorporated herein by reference.

[0119] In some embodiments, the macroemulsion is processed by passing it through a homogenizer, such as an ultrasonic jet or probe homogenizer, at a flow rate of about 50 mL / min to about 9 L / min. In some embodiments, the macroemulsion passes through the homogenizer at a flow rate of about 100 mL / min to about 1000 mL / min, or about 100 mL / min to about 500 mL / min, for example, about 150 mL / min to about 250 mL / min.

[0120] In some embodiments, the macroemulsion is ultrasonically treated (for example, by an ultrasonic jet or probe homogenizer) at amplitudes of about 1 μm to about 100 μm, for example, about 50 μm to about 90 μm, or for example, about 75 μm to about 85 μm.

[0121] In some embodiments, the macroemulsion is processed at a temperature of about 50°C or less (for example, using a homogenizer such as an ultrasonic jet or probe homogenizer). In some embodiments, the macroemulsion is processed at a temperature of about 20°C to about 50°C, for example, about 20°C to about 40°C, for example, about 25°C to about 35°C (for example, using a homogenizer such as an ultrasonic jet or probe homogenizer). In some embodiments, the macroemulsion passes through a homogenizer (for example, an ultrasonic jet or probe homogenizer) in the above temperature range.

[0122] In some embodiments, the resulting nanoemulsion may be passed through a filter to remove particles or droplets of the dispersed phase that are not in the nanoparticle range. As described above, the nanoemulsions described herein generally contain nanoscale particles having an average size of about 10 nm to about 1,000 nm. Therefore, in some embodiments, (d) includes passing the resulting nanoemulsion through a filter system to provide a final nanoemulsion containing a dispersed phase having an average particle size of about 10 nm to about 1,000 nm. The filter system may have an aperture size of about 1,000 nm or less to yield a desired particle size distribution in the nanoemulsion. In some embodiments, the filter system has an aperture size of about 500 nm or less to yield a nanoemulsion containing a dispersed phase having an average particle size of about 10 nm to about 500 nm.

[0123] whole method In some embodiments, the method further includes the step of adding one or more additives to the nanoemulsion. The additive may be combined with oil in the oil phase. Alternatively or additionally, the additive may be combined with water in the aqueous phase. Alternatively or additionally, the additive may be combined with the mixture obtained after (c). In other words, the additive may be added to the macroemulsion. Alternatively or additionally, the additive may be combined with the mixture obtained after (d). In other words, the additive may be added to the nanoemulsion itself.

[0124] One or more additives may be selected from the group consisting of flavoring agents (or "flavoring agents"), taste modifiers, preservatives, humectants, sweeteners, binders, buffers, salts, and mixtures thereof.

[0125] Flavoring agents and taste modifiers In some embodiments, the method further includes the step of adding a flavoring agent to the oil phase, aqueous phase, and / or both phases in a macroemulsion or nanoemulsion. As used herein, the terms “flavor” and “flavoring agent” refer to materials that may be used to create a desired taste, aroma, or other somatic sensation in a product intended for adult consumers, where permitted by local regulations. Examples of sensory properties that may be altered by flavoring agents include taste, mouthfeel, moisture, cold / hot, and / or aroma / fragrance. Flavoring agents may be natural or synthetic, and the flavor characteristics they impart may be described, but are not limited to, fresh, sweet, herbaceous, confectionery, floral, fruity, or savory.

[0126] Flavorings include naturally derived flavorings, botanicals, extracts of botanical medicines, synthetically obtained materials, or combinations thereof (for example, tobacco, cannabis, licorice, hydrangea, eugenol, magnolia leaves, chamomile, fenugreek, clove, maple, matcha, menthol, mint, anise, cinnamon, turmeric, Indian spices, Asian spices, herbs, Ardisia crenata, cherries, berries, red berries, cranberries, peaches, apples, oranges, mangoes, clementines, lemons, limes, tropical fruits, papaya, rhubarb, grapes, durian, dragon fruit, cucumbers, blueberries, mulberries, citrus fruits, drambuie). Bourbon, Scotch, Whiskey, Gin, Tequila, Rum, Spearmint, Peppermint, Lavender, Aloe Vera, Cardamom, Celery, Cascarilla, Nutmeg, Sandalwood, Bergamot, Geranium, Carthamus, Naswar, Betel, Shisha, Pine, Honey Essence, Rose Oil, Vanilla, Lemon Oil, Orange Oil, Orange Blossom, Cherry Blossom, Cassia, Dwarf Fennel, Cognac, Jasmine, Ylang-Ylang, Sage, Fennel, Wasabi, Pimento, Ginger, Coriander, Coffee, Hemp, Mentha Oil (any species of Mentha), Eucalyptus, Star Anise, Cocoa, Lemongrass, Rooibos, Flax, Ginkgo BilobaBiloba, hazelnut, hibiscus, bay laurel, mate tea, orange peel, rose, green and black tea, thyme, juniper, elderflower, basil, bay laurel leaves, cumin, oregano, paprika, rosemary, saffron, lemon peel, mint, shiso, turmeric, cilantro, myrtle, blackcurrant, valerian, pimento, mace, damien, marjoram, olive, lemon balm, lemon basil, chives, carvi, barbecue The flavorings may include (na, tarragon, limonene, thymol, camphene), umami flavorings, bitter taste receptor site blockers, sensory receptor site activators or stimulants, sugars and / or sugar substitutes (e.g., sucralose, acesulfame potassium, aspartame, saccharin, cyclamate, lactose, sucrose, glucose, fructose, sorbitol, or mannitol), and other additives, such as charcoal, chlorophyll, minerals, botanicals, or breath fresheners. These flavorings may be imitations, synthetic or natural ingredients, or blends thereof. They may be in any preferred form, such as liquids such as oils, solids such as powders, or gases.

[0127] In some embodiments, the flavor includes menthol, spearmint, and / or peppermint. In some embodiments, the flavor includes flavor components of cucumber, blueberry, citrus fruit, and / or red berry. In some embodiments, the flavor includes eugenol. In some embodiments, the flavor includes flavor components extracted from tobacco. In some embodiments, the flavor includes flavor components extracted from cannabis.

[0128] In some embodiments, the flavor may include sensory stimulants intended to achieve somatosensory perception, which is usually chemically induced and perceived by stimulation of the fifth cranial nerve (trigeminal nerve), in addition to or instead of the aromatic or gustatory nerves, and these sensory stimulants may include agents that produce heating, cooling, tingling, or paralyzing effects. A preferred thermal agent may be, but is not limited to, vanillyl ethyl ether, and a preferred cooling agent may be, but is not limited to, eucalyptol or WS-3.

[0129] In some embodiments, flavorings are lipophilic. While we do not wish to be bound by theory, the formulation of lipophilic flavorings as emulsions may enhance the stability of the flavorings (e.g., against oxidation or evaporation). In some embodiments, flavorings are susceptible to oxidation. This means that when exposed to air, the components of the flavorings degrade due to chemical changes. Examples of functional groups that may be present in oxidizable flavoring components include, but are not limited to, alkenes, aldehydes, and / or ketones. In some embodiments, flavorings include citrus oil. Citrus oils contain terpene components that are susceptible to oxidation, evaporation, or both, and therefore, their inclusion in products in the form of emulsions provided herein may be particularly beneficial.

[0130] In some embodiments, the flavoring agent may include terpenes. In some embodiments, the terpenes are terpenes that can be derived from phytocannabinoid-producing plants, such as strains of cannabis species, such as hemp. Suitable terpenes in this regard include so-called "C10" terpenes, which are terpenes containing 10 carbon atoms, and so-called "C15" terpenes, which are terpenes containing 15 carbon atoms. In some embodiments, the nanoemulsion or oral product containing the nanoemulsion contains two or more terpenes. For example, the nanoemulsion or oral product containing the nanoemulsion may contain one, two, three, four, five, six, seven, eight, nine, ten or more terpenes as defined herein. In some embodiments, the terpenes are selected from pinene (α and β), geraniol, linalool, limonene, carvone, eucalyptol, menthone, isomentone, piperitone, myrcene, β-bulbonene, germacrene, and mixtures thereof.

[0131] The amount of flavoring agent used in the emulsion can vary, but is typically up to about 10% by weight, and certain embodiments are characterized by a flavoring agent content of at least about 0.1% by weight, for example, about 0.5% to about 10% by weight, about 1% to about 6% by weight, or about 2% to about 5% by weight, based on the total weight of the emulsion.

[0132] In some embodiments, the method further includes the step of adding a flavor modifier to the oil phase, aqueous phase, and / or both phases in a macroemulsion or nanoemulsion. In some embodiments, the flavor modifier can mask the bitterness of cannabinoids in the emulsion. The flavor modifier can improve the sensory stimulation properties of the nanoemulsions disclosed herein and may help, for example, mask, modify, block, or improve the flavor of the compositions described herein. Non-limiting examples of such flavor modifiers include analgesic or anesthetic herbs, spices, and flavors that produce a perceived cooling sensation (e.g., menthol, eucalyptus, mint), a warming sensation (e.g., cinnamon), or a painful sensation (e.g., capsaicin). Certain flavor modifiers fall into several overlapping categories.

[0133] 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 contains a taste modifier that masks or blocks the perception of bitterness. In some embodiments, the taste modifier is a substance that targets pain receptors (e.g., vanilloid receptors) in the user's mouth to mask the bitterness of another component (e.g., a cannabinoid). In some embodiments, the taste modifier is capsaicin.

[0134] In some embodiments, the taste modifier is the amino acid γ-aminobutyric acid (GABA), as referred to herein above. Studies in mice suggest that GABA may play a role in taste bud function in addition to synaptic inhibition. See, for example, Dvoryanchikov et al., J Neurosci., April 13, 2011, Vol. 31 (No. 15), pp. 5782-91. While not bound by theory, GABA may suppress the perception of certain tastes, such as bitterness. In some embodiments, the composition comprises caffeine and GABA.

[0135] In some embodiments, the taste modifier is adenosine monophosphate (AMP). AMP is a naturally occurring nucleotide substance that can block the bitter flavor of foods or enhance sweetness. While AMP does not directly alter the bitter taste, it can alter the human perception of "bitter" by blocking the associated receptors.

[0136] In some embodiments, the taste modifier is lactizol. Lactizol is an antagonist of sweet taste receptors. Temporarily blocking sweet taste receptors can, for example, enhance savory flavors.

[0137] If present, typical amounts of flavor modifiers are approximately 0.01% by weight or more, approximately 0.1% by weight or more, or approximately 1.0% by weight or more, but usually account for less than approximately 10% by weight of the total weight of the nanoemulsion (for example, approximately 0.01% by weight, approximately 0.05% by weight, approximately 0.1% by weight, or approximately 0.5% to approximately 1% by weight, approximately 5% by weight, or approximately 10% by weight of the total weight of the nanoemulsion).

[0138] In some embodiments, the taste modifier is selected from the group consisting of analgesic or anesthetic herbs, spices, or flavors that produce a perceived cooling or warming effect, gamma-aminobutyric acid, capsaicin, and adenosine monophosphate. In some embodiments, the taste modified by the taste modifier is bitter, sweet, salty, or sour. In some embodiments, the taste is bitter. In some embodiments, the taste modifier is capsaicin.

[0139] Humectant In some embodiments, the method further includes the step of adding a wetting agent to the oil phase, the aqueous phase, and / or both phases in a macroemulsion or nanoemulsion. One or more wetting agents may be used in the emulsions of the present disclosure. The wetting agents may be present in the aqueous phase and / or oil phase of the emulsion.

[0140] Examples of wetting agents include, but are not limited to, glycerin, 1,2-propanediol (propylene glycol), 1,3-propanediol, dipropylene glycol, sorbitol, xylitol, and mannitol. In some embodiments, the wetting agent is glycerin or contains glycerin. In some embodiments, the oral product contains glycerin. In some embodiments, the emulsion contains glycerin. In some embodiments, the wetting agent is propylene glycol or contains propylene glycol. In some embodiments, the oral product contains propylene glycol. In some embodiments, the emulsion contains propylene glycol.

[0141] If included, the wetting agent is typically provided in an amount sufficient to impart the desired moisture properties to the composition. Furthermore, in some cases, the wetting agent can impart desirable flow properties to the composition for deposition within the mold.

[0142] If present in the emulsion, the wetting agent (e.g., glycerin and / or propylene glycol) may be present in amounts of about 0.1% to about 40% by weight of the emulsion, for example, about 1% to about 35% by weight of the emulsion, for example, about 5% to about 30% by weight of the emulsion, for example, about 10% to about 30% by weight of the emulsion, for example, about 15% to about 30% by weight of the emulsion, for example, about 20% to about 25% by weight of the emulsion.

[0143] Sweetener In some embodiments, the method further includes the step of adding a sweetener to the oil phase, the aqueous phase, and / or both phases in a macroemulsion or nanoemulsion. One or more sweeteners may be added to improve the sensory properties of the emulsion or oral product containing the emulsion according to the present disclosure. The sweetener may be any sweetener or combination of sweeteners, in natural or artificial form, or as a combination of natural and artificial sweeteners. Examples of natural sweeteners include fructose, sucrose, glucose, maltose, isomaltulose, mannose, galactose, lactose, stevia, honey, etc. Examples of artificial sweeteners include sucralose, maltodextrin, saccharin, aspartame, acesulfame K, neotame, etc. In some embodiments, the sweetener includes one or more sugar alcohols. Sugar alcohols are polyols derived from monosaccharides or disaccharides in a partially or fully hydrogenated form. Sugar alcohols, for example, have about 4 to about 20 carbon atoms and include erythritol, arabitol, ribitol, isomalt, maltitol, dalcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and combinations thereof (e.g., hydrogenated starch hydrolysates).

[0144] In some embodiments, the sweetener is selected from the group consisting of fructose, sucrose, glucose, maltose, mannose, galactose, lactose, stevia, honey, sucralose, isomaltulose, maltodextrin, saccharin, aspartame, acesulfame K, neotame, erythritol, arabitol, ribitol, isomalt, maltitol, dalcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and mixtures thereof. In some embodiments, the sweetener is selected from the group consisting of sucralose, acesulfame K, aspartame, maltodextrin, mannitol, sucrose, and mixtures thereof. In some embodiments, the sweetener may be sucralose and / or acesulfame K.

[0145] When present in the emulsion, sweeteners (e.g., sucralose and / or acesulfame K) may be present in amounts of about 0.01% to about 10% by weight of the emulsion, for example, about 0.1% to about 5% by weight of the emulsion, for example, about 0.5% to about 2.5% by weight of the emulsion, for example, about 1% to about 2.5% by weight of the emulsion.

[0146] Binder In some embodiments, the method further includes the step of adding a binder to the oil phase, aqueous phase, and / or both phases in a macroemulsion or nanoemulsion. The binder (or combination of binders) may be used in a quantity sufficient to provide the desired physical attributes and physical integrity to the composition in certain embodiments, and the binder also often functions as a thickener or gelling agent. Typical binders may be organic, inorganic, or a combination thereof. Representative binders include cellulose derivatives (e.g., cellulose ethers), povidone, sodium alginate, starch-based binders, pectin, gum, carrageenan, pullulan, zein, and combinations thereof. In some embodiments, the binder includes pectin or carrageenan or a combination thereof.

[0147] The amount of binder used in the composition can vary, but is typically up to about 30% by weight based on the total weight of the nanoemulsion, and certain embodiments are characterized by binder content of at least about 0.1% by weight, for example, about 1% to about 30% by weight, or about 1% to about 10% by weight.

[0148] In some embodiments, the binder includes a cellulose derivative. In certain embodiments, the cellulose derivative is a cellulose ether (e.g., a carboxyalkyl ether), which means a cellulose polymer in which one or more hydrogens of hydroxyl groups in the cellulose structure are replaced by alkyl, hydroxyalkyl, or aryl groups. Non-limiting examples of such cellulose derivatives include methylcellulose, hydroxypropylcellulose ("HPC"), hydroxypropylmethylcellulose ("HPMC"), hydroxyethylcellulose, and carboxymethylcellulose ("CMC"). In some embodiments, the cellulose derivative is one or more of methylcellulose, HPC, HPMC, hydroxyethylcellulose, and CMC. In some embodiments, the cellulose derivative is HPC. In some embodiments, the cellulose derivative is a combination of HPC and HPMC. In some embodiments, the nanoemulsion contains about 1% to about 10% by weight of the cellulose derivative based on the total weight of the nanoemulsion, and in certain embodiments, it contains about 1% to about 5% by weight of the cellulose derivative based on the weight of the nanoemulsion.

[0149] In certain embodiments, the binder includes gum, such as natural gum. As used herein, natural gum refers to naturally occurring polysaccharide materials that have binding properties and are also useful as thickeners or gelling agents. Typical plant-derived natural gums that are typically somewhat water-soluble include xanthan gum, guar gum, gum arabic, gatcha gum, tragacanth gum, karaya gum, locust bean gum, gellan gum, and combinations thereof. Where present, the natural gum binder material is typically present in amounts up to about 5% by weight, based on the total weight of the nanoemulsion, for example, about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, or about 1% to about 2, about 3, about 4, or about 5% by weight.

[0150] cushioning agent In some embodiments, the method further includes the step of adding a buffer to the oil phase, aqueous phase, and / or both phases in the macroemulsion or nanoemulsion. In fact, in certain embodiments, the emulsion or oral product containing the emulsion of this disclosure may contain a pH adjuster or buffer. Examples of pH adjusters and buffers that may be used include, but are not limited to, metal hydroxides (e.g., alkali metal hydroxides, e.g., sodium hydroxide and potassium hydroxide), and other alkali metal buffers, e.g., metal carbonates (e.g., potassium carbonate or sodium carbonate), or metal bicarbonates, e.g., sodium bicarbonate. If present, the buffer is typically present in an amount of less than about 5% by weight of the emulsion or oral product containing the emulsion, for example, about 0.5% to about 5% by weight, e.g., about 0.75% to about 4% by weight, about 0.75% to about 3% by weight, or about 1% to about 2% by weight, based on the total weight of the emulsion or oral product containing the emulsion.

[0151] Non-limiting examples of suitable buffers include alkali metal acetates, glycinates, phosphates, glycerophosphates, citrates, carbonates, bicarbonates, borates, or mixtures thereof. In some embodiments, the buffer is selected from the group consisting of sodium carbonate, sodium bicarbonate, sodium phosphate, ammonium phosphate, and mixtures thereof.

[0152] The oral products of this disclosure may have any preferred pH. In certain embodiments, the oral products of this disclosure have a pH of about 4 to about 7. In certain embodiments, the oral products of this disclosure have a pH of about 4 to about 6.5. In certain embodiments, the oral products of this disclosure have a pH of about 4.5 to about 7. In certain embodiments, the oral products of this disclosure have a pH of about 4.5 to about 6.5. In certain embodiments, the oral products of this disclosure have a pH of about 4 to about 6.5. In certain embodiments, the oral products of this disclosure have a pH of about 4.5 to about 6. In certain embodiments, the oral products of this disclosure have a pH of about 5 to about 6.

[0153] The pH of an oral product can be measured by any preferred technique. For example, the pH of an oral product can be measured by contacting 5 grams of the oral product with 95 g of water (100 g total) and then mixing for 5 minutes. After mixing, the pH of the solution can be measured with a pH probe.

[0154] The nanoemulsions according to this disclosure may have any preferred pH. In certain embodiments, the nanoemulsions of this disclosure have a pH of about 4 to about 7. In certain embodiments, the nanoemulsions of this disclosure have a pH of about 4.5 to about 7. In certain embodiments, the nanoemulsions of this disclosure have a pH of about 5 to about 7. In certain embodiments, the nanoemulsions of this disclosure have a pH of about 5.5 to about 7. In certain embodiments, the nanoemulsions of this disclosure have a pH of about 6 to about 7. In certain embodiments, the nanoemulsions of this disclosure have a pH of about 6 to about 6.5.

[0155] salt In some embodiments, the emulsions or oral products comprising emulsions according to this disclosure typically include a salt (e.g., an alkali metal salt) used in an amount sufficient to impart the desired sensory attributes to the product. Non-limiting examples of suitable salts include sodium chloride, potassium chloride, ammonium chloride, wheat flour salt, sodium acetate, sodium citrate, and the like. If present, a typical amount of salt is at least about 0.5% by weight, for example at least about 1% by weight, for example at least about 1.5% by weight. In some embodiments, the emulsion may contain an amount of salt ranging from about 0.5% to about 10% by weight, for example at about 1% to about 7.5% by weight, for example at about 1.5% to about 5% by weight, based on the total weight of the emulsion.

[0156] Stabilizer In some embodiments, the nanoemulsion may further contain stabilizers to help maintain the nanoemulsion. Typical examples of preferred types of stabilizers include polysaccharides, polyols, sorbitan esters, glycerol esters, polyethylene glycol esters, block polymers, acrylic polymers (e.g., pemlen), silicone-based surfactants, and polysorbates. In some embodiments, the stabilizer is sodium oleate, glycerin, xylitol, sorbitol, ascorbic acid, sodium edetate, sorbitan esters, glycerol monoesters, or a combination thereof.

[0157] The concentration of stabilizers present in the emulsion can vary. If present, the stabilizer concentration can range from approximately 10% by weight of the emulsion, for example, from approximately 0.01% to approximately 10% by weight, from approximately 0.1% to approximately 5% by weight, or from approximately 0.5% to approximately 1% by weight.

[0158] Other additives In some embodiments, the method further includes the step of adding other additives to the oil phase, the aqueous phase, and / or both phases in the macroemulsion or nanoemulsion. For example, in some embodiments, the method further includes the step of adding a preservative to the oil phase, the aqueous phase, and / or both phases in the macroemulsion or nanoemulsion.

[0159] For example, an emulsion or an oral product containing an emulsion may be processed, blended, formulated, combined, and / or mixed with other materials or ingredients. Additives may be artificial, or obtained or derived from herbs or biological sources. Examples of further types of additives include thickeners or gelling agents (e.g., fish gelatin), preservatives (e.g., potassium sorbate, sodium benzoate, calcium propionate, etc.), disintegrants, and substances selected to be relatively water-soluble (e.g., magnesium or zinc gluconate, or relatively water-insoluble (e.g., magnesium or zinc oxide, zinc or magnesium salts, or combinations thereof) for compositions that are more water-soluble). For further details on embodiments and methods, see, for example, U.S. Patent No. 9,237,769 (Mua et al.), U.S. Patent No. 7,861,728 (Holton, Jr. et al.), U.S. Patent Application Publication No. 2010 / 0291245 (Gao et al.), and U.S. Patent Application Publication No. 2007 / 0062549 (Holton, Jr. et al.), which are incorporated herein by reference, respectively. Typical ranges of such additional additives may vary depending on the nature and function of the additive and the intended effect on the final composition, with exemplary ranges being up to about 10% by weight (e.g., about 0.1% to about 5% by weight) based on the total weight of the emulsion.

[0160] For example, if present, preservatives (e.g., potassium sorbate, sodium benzoate, calcium propionate, etc.) may be included in the emulsion in amounts of approximately 0.01% to 5% by weight of the emulsion, for example, approximately 0.05% to 2.5% by weight of the emulsion, for example, approximately 0.1% to 1% by weight of the emulsion.

[0161] Colorants may be used in amounts sufficient to impart the desired physical attributes to the emulsion or oral product containing the emulsion according to this disclosure. Examples of colorants include various dyes and pigments, such as caramel color and titanium dioxide. The amount of colorant used in the emulsion or oral product containing the emulsion may vary, but if present, it is typically up to about 3% by weight, for example, about 0.1% by weight, about 0.5% by weight, or about 1% to about 3% by weight, based on the total weight of the emulsion.

[0162] The aforementioned additives may be used together (for example, as an additive formulation) or separately (for example, individual additive components may be added at different stages involved in the preparation of the final product). Furthermore, the aforementioned types of additives may be encapsulated when provided to the final product or composition. Exemplary encapsulated additives are described, for example, in WO2010 / 132444 (Atchley), which is incorporated herein by reference.

[0163] Nanoemulsion According to some embodiments described herein, a nanoemulsion comprising at least one cannabinoid, (a) A step of providing an oil phase containing at least one cannabinoid, (b) A step of providing an aqueous phase, (c) A process of combining the oil phase and the aqueous phase to form a macroemulsion, (d) Process to form nanoemulsions by processing macroemulsions. Includes, At least one of the oil phase and the aqueous phase contains one or more emulsifiers. Nanoemulsions obtained or obtainable by the method are provided.

[0164] The nanoemulsion may be obtained or obtainable by the methods described in detail above herein.

[0165] The nanoemulsions described herein can be characterized by reference to a polydispersity index. Polydispersity indicates the uniformity of droplet diameter of the nanoemulsion. A higher polydispersity value indicates lower uniformity of droplet diameter. This can be defined as the ratio of the standard deviation to the mean droplet diameter. This ratio can be measured by spectrophotometry. In some embodiments, it may be advantageous to provide nanoemulsions with a low polydispersity index, e.g., less than about 0.5. In some embodiments, the nanoemulsions have a polydispersity index of less than about 0.3.

[0166] The nanoemulsions described herein generally contain nanoscale particles having an average size of about 10 nm to about 1,000 nm, for example, about 10 nm to about 200 nm, about 20 nm to about 100 nm, or about 40 nm to about 100 nm. In some embodiments, the average particle size is about 100 nm, about 90 nm, about 80 nm, about 70 nm, about 60 nm, about 50 nm, or about 40 nm. In some embodiments, the average particle size is about 40 nm to about 80 nm. In some embodiments, the average particle size is about 40 nm to about 80 nm, and the nanoemulsion is transparent.

[0167] In some embodiments, the nanoemulsion comprises nanoparticles or nanodroplets of an oil phase dispersed in an aqueous phase. In some embodiments, the nanodroplets have an average diameter (or average size) of about 1 nm to about 500 nm, for example, about 1 nm to about 200 nm, for example, about 10 nm to about 200 nm.

[0168] The nanoemulsions described herein may be characterized by reference to their zeta potential. Zeta potential is a measure of the charge on the surface of droplets in an emulsion (or nanoemulsion). In some embodiments, the zeta potential of nanoparticles is less than about -10 mV. In some embodiments, the zeta potential of nanoparticles is less than about -20 mV. In some embodiments, the zeta potential of nanoparticles is less than about -30 mV. In some embodiments, the zeta potential of nanoparticles is less than about -40 mV. In some embodiments, the zeta potential of nanoparticles is less than about -50 mV. In some embodiments, the zeta potential of nanoparticles is in the range of about -100 mV to about -10 mV, e.g., about -100 mV to about -20 mV, e.g., about -100 mV to about -30 mV, e.g., about -100 mV to about -40 mV, e.g., about -100 mV to about -50 mV. As will be understood by those skilled in the art, the zeta potential is a measure of the electric charge on the surface of particles in a colloidal dispersion. The zeta potential can be measured with a zeta analyzer, such as a Malvern Zetasizer.

[0169] As described herein, the nanoemulsion comprises an oil phase and an aqueous phase. The emulsion further comprises at least one cannabinoid contained in the oil phase.

[0170] Nanoemulsions may include an oil phase as a continuous phase or a dispersed phase. Nanoemulsions may include an aqueous phase as a continuous phase or a dispersed phase. In some embodiments, the emulsion includes an oil phase as a continuous phase and an aqueous phase as a dispersed phase (i.e., a water-in-oil emulsion). In some embodiments, the nanoemulsion includes an aqueous phase as a continuous phase and an oil phase as a dispersed phase (i.e., an oil-in-water emulsion). In some embodiments, the nanoemulsion may be a water-in-oil emulsion. In some embodiments, the emulsion may be an oil-in-water emulsion.

[0171] In some embodiments, the emulsion is an oil-in-water emulsion, and the cannabinoids are present in the dispersed oil phase. In some embodiments, the emulsion is a water-in-oil emulsion, and the cannabinoids are present in the continuous oil phase.

[0172] In some embodiments, the emulsion is a nanoemulsion containing nanoparticles of an oil phase dispersed in an aqueous phase. In some embodiments, the cannabinoid is present within the nanoparticles of the oil phase in the nanoemulsion.

[0173] In some embodiments, cannabinoids (e.g., cannabidiol) are present in the nanoemulsion at a concentration of at least about 0.001% by weight of the emulsion, for example, in the range of about 0.001% to about 30% by weight of the emulsion. In some embodiments, cannabinoids (e.g., cannabidiol) are present at a concentration of about 0.1% to about 20% by weight based on the total weight of the emulsion. In some embodiments, cannabinoids (e.g., cannabidiol) are present at a concentration of about 0.1% to about 10% by weight, for example, about 0.5% to about 10% by weight, for example, about 1% to about 10% by weight, or about 1% to about 5% by weight, based on the total weight of the emulsion. In some embodiments, cannabinoids (e.g., cannabidiol) are present at a concentration of about 2.5% to about 15% by weight, for example, about 5% to about 15% by weight, or for example, about 5% to about 10% by weight, based on the total weight of the emulsion.

[0174] In some embodiments, the weight ratio of oil to cannabinoid (e.g., cannabidiol) in the nanoemulsion is about 10:1 to about 1:10, for example about 5:1 to about 1:5, for example about 3:1 to about 1:3, for example about 3:1 to about 1:1, for example about 2:1 to about 1:1.

[0175] In some embodiments, the weight ratio of water to cannabinoid (cannabidiol) in the nanoemulsion is about 20:1 to about 1:10, for example, about 15:1 to about 1:1, for example, about 10:1 to about 1:1, for example, about 8:1 to about 5:1.

[0176] To avoid any doubt, the above endpoint combinations are expressly assumed by this disclosure. This applies to any scope disclosed herein.

[0177] According to some embodiments described herein, (a) an oil phase containing at least one cannabinoid, (b) Water phase A nanoemulsion containing, At least one of the oil phase and the aqueous phase contains one or more emulsifiers, and the zeta potential of the nanoemulsion is less than approximately -10 mV. Nanoemulsions are provided.

[0178] The nanoemulsion may be obtained or obtainable by the methods described in detail above herein. The nanoemulsion may have any of the characteristics described above herein.

[0179] oral products According to some embodiments described herein, an oral product comprising a nanoemulsion containing at least one cannabinoid, wherein the nanoemulsion is (a) obtained or obtainable by the methods defined herein, or (b) (i) an oil phase containing at least one cannabinoid, (ii) aqueous phase Includes, At least one of the oil phase and the aqueous phase contains one or more emulsifiers. The zeta potential of the nanoemulsion is less than approximately -10mV. Oral products are provided.

[0180] Oral products are designed for oral use and are therefore designed for insertion into the user's mouth (i.e., oral cavity).

[0181] The amount of nanoemulsion in the oral product can vary and may be any suitable amount for forming a product suitable for oral use. In some embodiments, the nanoemulsion is present in the oral product in amounts of about 1% to about 75% by weight of the oral product, for example, about 5% to about 60% by weight of the oral product, for example, about 10% to about 50% by weight of the oral product, for example, about 15% to about 45% by weight of the oral product, for example, about 20% to about 40% by weight of the oral product, for example, about 25% to about 40% by weight of the oral product, for example, about 30% to about 40% by weight of the oral product.

[0182] In some embodiments, the nanoemulsion is present in the oral product in an amount of about 20% to about 40% by weight.

[0183] Therefore, in some embodiments, cannabinoids (e.g., cannabidiol) are present in the oral product at a concentration of at least about 0.001% by weight, for example, in the range of about 0.001% to about 20% by weight of the oral product. In some embodiments, cannabinoids are present in the oral product at a concentration of about 0.1% to about 15% by weight, based on the total weight of the oral product. In some embodiments, cannabinoids (e.g., cannabidiol) are present at a concentration of about 1% to about 15% by weight, for example, about 5% to about 15% by weight, based on the total weight of the oral product. In some embodiments, cannabinoids (e.g., cannabidiol) are present in the oral product at a concentration of about 0.5% to about 10% by weight, for example, about 1% to about 7.5% by weight, for example, 1.5% to about 5% by weight, for example, about 1.5% to about 2.5% by weight, based on the total weight of the oral product.

[0184] In some embodiments, the oral product further comprises a filler combined with a nanoemulsion. The emulsions disclosed herein can be associated with fillers in a variety of ways (i.e., in oral products comprising the emulsions disclosed herein). For example, the emulsion may be placed on the surface of the filler, dispersed or impregnated in the filler (e.g., adsorbed or absorbed), or the filler and emulsion may exist within the oral product without being physically combined or in physical contact (e.g., the filler and emulsion may be provided separately and independently within the same product).

[0185] Depending on the product and the relationship between the filler and the emulsion, fillers can perform multiple functions, such as enhancing specific sensory properties like texture and mouthfeel, and improving the cohesiveness or compressibility of the product.

[0186] In some embodiments, the filler is a porous particulate material and is cellulose-based. For example, the filler may be a non-tobacco plant material or a derivative thereof, and may also include cellulose materials derived from such sources. Examples of cellulosic non-tobacco plant materials include grains (e.g., corn, oats, barley, rye, buckwheat, etc.), sugar beets (e.g., FIBREX® brand fillers available from International Fiber Corporation), bran fibers, and mixtures thereof.

[0187] In some embodiments, the filler is a cellulose material selected from the group consisting of corn fiber, oat fiber, barley fiber, rye fiber, buckwheat fiber, sugar beet fiber, bran fiber, bamboo fiber, wood pulp fiber, cotton fiber, citrus pulp fiber, grass fiber, willow fiber, poplar fiber, cocoa fiber, derivatives thereof, and combinations thereof. In some embodiments, the filler is a cellulose material selected from the group consisting of corn fiber, oat fiber, sugar beet fiber, bamboo fiber, wood pulp fiber, cotton fiber, grass fiber, derivatives thereof, or combinations thereof. In some embodiments, the filler is a cellulose material selected from the group consisting of sugar beet fiber, wood pulp fiber, bamboo fiber, derivatives thereof, or combinations thereof.

[0188] In some embodiments, the filler is derived from any of the following: corn fiber, oat fiber, barley fiber, rye fiber, buckwheat fiber, sugar beet fiber, bran fiber, bamboo fiber, wood pulp fiber, cotton fiber, citrus pulp fiber, grass fiber, willow fiber, poplar fiber, cocoa fiber, or a combination thereof. In some embodiments, the filler is derived from wood pulp fiber.

[0189] In some embodiments, the filler is a cellulose material. One particularly suitable filler for use in the compositions described herein is microcrystalline cellulose ("MCC"). MCC is typically derived from wood pulp fibers. MCC is composed of glucose units linked by β-1,4 glycosidic bonds and can be synthesized by partially depolymerizing α-cellulose, for example, by reactive extrusion formation, enzyme-mediated depolymerization, mechanical grinding, sonication, steam explosion, and / or acid hydrolysis. MCC may be synthetic or semi-synthetic, or it may be obtained entirely from natural cellulose. MCC may be selected from the group consisting of AVICEL® grades PH-100, PH-101, PH-102, PH-103, PH-105, PH-112, PH-113, PH-200, PH-300, PH-301, PH-302, VIVACEL® grades 101, 102, 12, 20, and EMOCEL® grades 50M and 90M, as well as mixtures thereof. In some embodiments, the oral product contains MCC as a filler.

[0190] In some embodiments, the filler is a non-tobacco plant material or a derivative thereof. Non-limiting examples of derivatives of non-tobacco plant materials include starch (e.g., derived from potatoes, wheat, rice, and corn), natural cellulose, and modified cellulose materials. Examples of additional potential fillers include maltodextrin, dextrose, calcium carbonate, calcium phosphate, lactose, mannitol, xylitol, and sorbitol. Combinations of multiple fillers may also be used.

[0191] As used herein, “starch” may refer to pure starch, modified starch, or starch derivatives from any source. Starch is typically granular and is present in almost all green plants as well as in various types of plant tissues and organs (e.g., seeds, leaves, rhizomes, roots, tubers, sprouts, fruits, grains, and stems). Starch varies not only in composition but also in particle shape and size. Often, starches from different sources have different chemical and physical properties. Specific starches may be selected for inclusion in a composition based on their ability to impart particular sensory properties to the composition. Starches from various sources may be used. For example, the main sources of starch include grains (e.g., rice, wheat, and maize) and root vegetables (e.g., potatoes and cassava). Other examples of starch sources include acorns, arrowroot, arakacha, bananas, barley, legumes (e.g., broad beans, lentils, double peas, peas, chickpeas), breadfruit, buckwheat, canna, chestnut, colocasia, dogtooth violet, kudzu, maranga, millet, oats, oka, Polynesian arrowroot, sago, sorghum, sweet potato, quinoa, rye, tapioca, taro, tobacco, water chestnut, and yam. Certain starches are modified starches. Modified starches undergo one or more structural modifications, often designed to alter their high-temperature properties. Some starches are developed through genetic engineering and are considered "genetically modified" starches. Other starches are modified after they are obtained by chemical, enzymatic, or physical means. For example, modified starch may be starch subjected to chemical reactions such as esterification, etherification, oxidation, depolymerization (dilution) by acid-catalyzed or oxidation in the presence of a base, bleaching, glycosyl transfer and depolymerization (e.g., dextrinization in the presence of a catalyst), crosslinking, acetylation, hydroxypropylation, and / or partial hydrolysis. Enzymatic treatment includes modifying corn starch by subjecting natural starch to enzyme isolates or concentrates, microbial enzymes, and / or enzymes naturally present in plant materials, such as amylase present in corn kernels.Other starches are modified by heat treatments such as gelatinization, dextrinization, and / or cold water swelling processes. Specific modified starches include phosphorylated starch, glycerol cross-linked starch, phosphate cross-linked starch esterified with sodium trimetaphosphate, phosphate monoesterified phosphate cross-linked starch, acetylated phosphate cross-linked starch, acetate starch esterified with acetic anhydride, acetate starch esterified with vinyl acetate, acetylated adipic acid cross-linked starch, acetylated glycerol cross-linked starch, hydroxypropyl starch, hydroxypropyl glycerol cross-linked starch, and sodium octenyl succinate starch.

[0192] The amount of filler can vary, but if present, it is typically at least about 50 weight percent of the oral product, based on the total weight of the oral product, including the emulsion. The typical range of filler (e.g., MCC) in the composition may be about 10 to about 75 weight percent of the total weight of the oral product. For example, filler (e.g., MCC) may be present in the oral product in an amount of at least about 50 weight percent of the oral product, for example, at least about 55 weight percent of the oral product, for example, at least about 60 weight percent of the oral product. In some embodiments, filler (e.g., MCC) may be present in the oral product in an amount of about 50 to about 99 weight percent of the oral product, for example, about 50 to about 95 weight percent of the oral product, for example, about 50 to about 90 weight percent of the oral product, for example, about 55 to about 85 weight percent of the oral product, for example, about 60 to about 80 weight percent of the oral product, for example, about 60 to about 75 weight percent of the oral product.

[0193] In some embodiments, the oral product contains microcrystalline cellulose in an amount of about 55% to about 95% by weight of the oral product. In some embodiments, the oral product contains microcrystalline cellulose in an amount of about 55% to about 80% by weight of the oral product.

[0194] In some embodiments, the weight ratio of filler (e.g., microcrystalline cellulose) to nanoemulsion can be about 10:1 to about 1:10, for example about 5:1 to about 1:5, for example about 5:1 to about 1:2, for example about 3:1 to about 1:1, for example about 2:1 to about 1:1.

[0195] In some embodiments, the weight ratio of filler (e.g., microcrystalline cellulose) to cannabinoid is about 5:1 to about 100:1, for example, about 10:1 to about 60:1, for example, about 15:1 to about 50:1, for example, about 20:1 to about 40:1, for example, about 25:1 to about 35:1. In some embodiments, the weight ratio of microcrystalline cellulose to cannabidiol is about 5:1 to about 100:1, for example, about 10:1 to about 60:1, for example, about 15:1 to about 50:1, for example, about 20:1 to about 40:1, for example, about 25:1 to about 35:1.

[0196] In some embodiments, the oral product contains water. In some embodiments, the water content of the oral product is at least about 10% by weight. In some embodiments, the water content is less than about 30% by weight. Where used herein, “water content” means the total amount of water in the oral product, whether in any form. Water may be present, for example, as purified water or ultrapure water, saline solution, buffered saline solution, or a buffered aqueous phase.

[0197] In some embodiments, the only water present in the composition is contained within the emulsion in the product.

[0198] In some embodiments, the oral product has a water content of about 10% to about 30% by weight of the oral product, for example, about 10% to about 25% by weight of the oral product, for example, about 10% to about 20% by weight of the oral product, for example, about 11% to about 15% by weight of the oral product. In some embodiments, the oral product has a water content of about 12% to about 30% by weight of the oral product, for example, about 13% to about 25% by weight of the oral product, for example, about 14% to about 25% by weight of the oral product, for example, about 15% to about 20% by weight of the oral product.

[0199] In some embodiments, the weight ratio of filler to water is about 1:1 to about 20:1, for example, about 1:1 to about 10:1, for example, about 2:1 to about 5:1, for example, about 3:1 to about 5:1.

[0200] Configuration for oral use In some embodiments, oral products may be solid oral products. “Solid” means a composition that can substantially maintain its physical shape when not supported by external means, such as packaging. Therefore, they are considered to be solid, solid-like, solid-form, or solid-like-form at room temperature. To avoid doubt, solid products must remain substantially solid up to 30°C.

[0201] Regarding solid-like properties, some materials are considered solid in everyday life, but it is understood that their shape may change over very long periods of time. For example, amorphous materials such as glass. However, these materials are considered solid-like because they are solid for the purpose they serve.

[0202] The emulsions and compositions and products containing emulsions described herein are configured for oral use. As used herein, “configured for oral use” means that the product is provided in such a form that, during use, one or more of the components of the emulsion, composition, or product (e.g., flavoring agents and / or active ingredients) enter the user’s mouth through the user’s saliva. In certain embodiments, the emulsion, composition, or product is adapted to deliver the components to the user via the mucous membranes of the user’s mouth, the user’s digestive system, or both, and in some cases, the components are active ingredients that are absorbed through the mucous membranes of the mouth or through the digestive tract when the product is used.

[0203] Products configured for oral use as described herein (incorporating the disclosed emulsions) are in solid form. Products may take various forms, such as lozenges, gums, drops, tablets, and powders. Products may be supplied in pouch form, in which the solid oral product (e.g., powder) is incorporated into the pouch.

[0204] Certain products configured for oral use take the form of lozenges. As used herein, the term “lozenge” refers to a soluble oral product made by solidifying a liquid or gel composition, resulting in the final product being a somewhat hardened solid gel. The stiffness of the gel varies considerably. Certain products may exhibit one or more of the following characteristics, for example: crunchy, granular, chewy, syrupy, paste-like, fluffy, smooth, and / or creamy. In certain embodiments, the desired texture property may be selected from the group consisting of stickiness, cohesiveness, density, dryness, fragility, granularity, gumminess, hardness, weight, hygroscopicity, hygroscopicity, stickiness to the mouth, roughness, slipperiness, smoothness, viscosity, wetness, and combinations thereof.

[0205] Products containing the emulsions of this disclosure may be soluble. As used herein, the terms “dissolve,” “dissolving,” and “dissolvable” refer to compositions having water-soluble components that interact with moisture in the mouth, enter the solution, and thereby cause the product to be gradually consumed. According to one embodiment, a soluble product may remain in the user’s mouth for a given period of time until it is completely dissolved. The rate of dissolution can vary in a wide range from about 1 minute or less to about 60 minutes. For example, a fast-release composition typically dissolves and / or releases the active substance in about 2 minutes or less, often about 1 minute or less (e.g., about 50 seconds or less, about 40 seconds or less, about 30 seconds or less, or within about 20 seconds). Dissolution may occur by any means such as melting, mechanical destruction (e.g., chewing), enzymatic or other chemical decomposition, or by disruption of interactions between the components of the composition. In some embodiments, the product may be meltable, as discussed, for example, in U.S. Patent Application Publication No. 2012 / 0037175 (Cantrell et al.). In other embodiments, the product does not melt while it remains in the user's mouth.

[0206] In some embodiments, the oral product may be in the form of a powder. The powder may be a free-flowing powder. The powder may be contained in a loose form in a container and thus used in a snuff-like manner, where the user picks up the powder from the container and puts it into their mouth. Alternatively or additionally, the powder may be incorporated into a moisture-permeable (e.g., saliva-permeable) pouch, similar to snus-type products. The pouch-packaged product may be configured to be inserted into the user's mouth.

[0207] According to some embodiments described herein, pouch-packaged oral products are provided, including a saliva-permeable pouch and an oral product as defined herein incorporated within the pouch.

[0208] In some embodiments, the products of the present disclosure take the form of pouch-packaged oral products. Such pouch-packaged products include solid oral products containing the emulsion described herein, disposed in a moisture-permeable container (e.g., a water-permeable pouch or a saliva-permeable pouch). For example, a pouch-packaged product may include a solid oral product in powder form incorporated into a saliva-permeable pouch.

[0209] Accordingly, according to some embodiments described herein, a pouch-packaged oral product is provided, comprising a saliva-permeable pouch and an oral product incorporated within the pouch, wherein the oral product is in powder form and comprises an emulsion comprising a continuous phase and a dispersion, the emulsion comprising cannabinoids.

[0210] Such compositions in the form of a breathable pouch are typically used by placing one pouch containing the composition into the mouth of a human subject / user. Generally, the pouch is placed somewhere in the user's mouth, for example, below the lip, as is commonly done with moist snuff products. It is preferable that the pouch is not chewed or swallowed. Then, upon exposure to saliva, some of the components of the composition within it (e.g., flavorings and / or active ingredients) pass through, for example, the breathable pouch, providing the user with flavor and satisfaction, and the user does not need to spit out any part of the composition. After use / enjoyment for about 10 to 60 minutes, usually about 15 to 45 minutes, a considerable amount of the composition has been ingested by the human subject, and the pouch can be removed from the human subject's mouth for disposal.

[0211] Accordingly, in certain embodiments, the emulsions disclosed herein and any other optional components described above are combined in a hygroscopic packet or pouch that acts as a container for use of the composition to provide a pouched product configured for oral use. Certain embodiments of the disclosure are described with reference to Figure 1 of the accompanying drawings, and these described embodiments include a snus-type product having an outer pouch and containing the composition described herein. As will be described in more detail below, such embodiments are provided only as examples, and the pouched products of the disclosure may include other forms of composition. The composition / structure of such packets or pouches, such as container pouch 102 in the embodiment shown in Figure 1, may vary. Referring to Figure 1, a first embodiment of pouched product 100 is shown. Pouched product 100 comprises a hygroscopic container in the form of pouch 102, which contains an oral product 104 containing the cellulose material and cannabinoids described herein.

[0212] In some embodiments, the pouch is saliva permeable. This means that the pouch is made from a saliva permeable pouch material. In some embodiments, the pouch material is a fleece material. In some embodiments, the pouch material is a nonwoven fabric material. In some embodiments, the pouch material is a nonwoven fleece material. In some embodiments, the pouch material contains viscose, such as viscose rayon fibers. In some embodiments, the pouch material contains regenerated cellulose fibers. In some embodiments, the pouch material contains polyester fibers. Polyester fibers may constitute the pouch material or may be included in combination with viscose (e.g., regenerated cellulose fibers).

[0213] In some embodiments, the pouch material includes a binder that allows the pouch to be heat-sealed during manufacturing. In some embodiments, the pouch material includes an acrylic binder. In some embodiments, the pouch material includes an acrylic binder combined with viscose and / or polyester fibers.

[0214] Suitable packets, pouches, or containers of the type used in the manufacture of smokeless tobacco products are available under the trade names CatchDry, Ettan, General, Granit, Goteborgs Rape, Grovsnus White, Metropol Kaktus, Mocca Anis, Mocca Mint, Mocca Wintergreen, Kicks, Probe, Prince, Skruf, and TreAnkrare. Compositions may be contained and packaged in pouches using and employing components of the type used in the manufacture of conventional snus-type products. The pouches provide a type of breathable container that is considered to have characteristics similar to the mesh-like material used in the construction of tea bags. The components of the composition readily diffuse through the pouch into the user's mouth.

[0215] Non-limiting examples of preferred types of pouches are described, for example, in U.S. Patent No. 5,167,244 (Kjerstad), U.S. Patent No. 8,931,493 (Sebastian et al.), and U.S. Patent Publications 2016 / 0000140 (Sebastian et al.), 2016 / 0073689 (Sebastian et al.), 2016 / 0157515 (Chapman et al.), and 2016 / 0192703 (Sebastian et al.), which are incorporated herein by reference, respectively. The pouches may be supplied as individual pouches, or multiple pouches (e.g., 2, 4, 5, 10, 12, 15, 20, 25, or 30 pouches) may be connected or linked together (e.g., end to end) so that a single pouch or individual part can be easily removed from the integrally formed strand or matrix of the pouch for use. The pouches may be formed from a breathable nonwoven fabric, such as viscose.

[0216] Exemplary pouches may be manufactured in materials and manner such that the pouch undergoes controlled dispersion or dissolution during use by the user. Such pouch materials may take the form of mesh, mesh screens, perforated paper, permeable cloth, etc. For example, a pouch material made from rice paper in a mesh form or from perforated rice paper may dissolve in the user's mouth. As a result, the pouch and composition will each be completely dispersed in the user's mouth during normal use, and thus both the pouch and composition may be ingested by the user. Other examples of pouch materials may be manufactured using water-dispersible film-forming materials (e.g., binders such as alginates, carboxymethylcellulose, xanthan gum, and pullulan), and combinations of these materials with materials such as pulverized cellulosic derivatives (e.g., fine-grained wood pulp). Preferred pouch materials may be water-dispersible or soluble, but designed and manufactured so that under normal use conditions, a substantial amount of composition contents permeates the pouch material before the pouch loses its physical integrity. If necessary, flavoring agents, disintegrants, and other desired ingredients may be incorporated into or applied to the pouch material.

[0217] The amount of oral product contained in each pouch-packaged product unit, for example, in a pouch, can vary. In some embodiments, the weight of the emulsion-containing composition in each pouch is at least about 50 mg, for example, about 50 mg to about 2 grams, about 100 mg to about 1.5 grams, or about 200 mg to about 700 mg. In some smaller embodiments, the weight of the composition in each pouch may be about 100 mg to about 300 mg. In larger embodiments, the weight of the material in each pouch may be about 300 mg to about 700 mg. Other components may be contained in each pouch as needed. For example, at least one flavored strip, fragment, or sheet of a flavored, water-dispersible or water-soluble material (for example, an edible film-type material for freshening breath) may be placed in each pouch with or without at least one capsule. Such strips or sheets may be folded or crumpled for easy assembly into the pouch. For example, see U.S. Patent No. 6,887,307 (Scott et al.) and No. 6,923,981 (Leung et al.), incorporated herein by reference; and the types of materials and technologies described in The EFSA Journal (2004), Vol. 85, pp. 1-32.

[0218] According to some embodiments described herein, a package containing an oral product as defined herein or at least one pouch-packaged oral product as defined herein is provided.

[0219] According to several embodiments described herein, a package containing the oral product described herein is provided. For example, the package may contain the oral product in powder form. In such embodiments, the package may take the form of a tin or plastic container. Alternatively or additionally, the package may include the oral product in the form of drops, lozenges, tablets, etc. The package may take the form of a blister pack, tin or plastic container containing such solid oral dosage forms.

[0220] According to some embodiments described herein, a package containing at least one pouch-packaged oral product described herein is provided. The pouch-packaged products described herein may be packaged in any suitable internal packaging material and / or external container. For example, U.S. Patents 7,014,039 (Henson et al.), 7,537,110 (Kutsch et al.), 7,584,843 (Kutsch et al.), 8,397,945 (Gelardi et al.), D592,956 (Thiellier), D594,154 (Patel et al.), and D625,178 (Bailey et al.), incorporated herein by reference, U.S. Patent Application Publication 2008 / 0173317 (Robinson et al.), 2009 / 0014343 (Clark et al.), and 2009 / 0014450 (Bjo See also the various types of containers for smokeless products described in rkholm, and in the same publications No. 2009 / 0250360 (Bellamah et al.), No. 2009 / 0266837 (Gelardi et al.), No. 2009 / 0223989 (Gelardi), No. 2009 / 0230003 (Thiellier), No. 2010 / 0084424 (Gelardi), and No. 2010 / 0133140 (Bailey et al.), No. 2010 / 0264157 (Bailey et al.), and No. 2011 / 0168712 (Bailey et al.). For example, the packaging may be a tin or plastic container containing multiple pouches of oral products.

[0221] Surprisingly, the inventors have found that when cannabinoids are included in oral products in the form of nanoemulsions obtained herein, the release characteristics of the cannabinoids and the rate of absorption into the oral mucosa are improved. As those skilled in the art will understand, cannabinoids are hydrophobic compounds that do not readily dissolve in water. This is especially true for crystalline CBD isolates. Therefore, previous cannabinoid-containing oral formulations have the disadvantage that the cannabinoids are not readily released from such formulations when placed in the user's mouth. Furthermore, due to their inherent lack of solubility, the cannabinoids were not readily absorbed into the oral mucosa. Rather, with such formulations, the user had to swallow the unabsorbed cannabinoids and deliver them to the user's digestive tract where the cannabinoids could be broken down and absorbed.

[0222] The inventors have found that incorporating cannabinoids into an emulsion overcomes the problems associated with their lack of water solubility. The cannabinoids are released from the oral product into the user's mouth relatively quickly. Furthermore, the cannabinoids are readily absorbed into the oral mucosa and thus into the bloodstream without the need to swallow the active ingredient. Therefore, the physiological effects of the active ingredient are felt by the user much more rapidly than with previously known formulations.

[0223] In some embodiments, when placed in the user's mouth, the oral product releases at least 50% by weight of cannabinoids within a maximum of approximately 60 minutes, for example, within approximately 45 minutes, for example, within approximately 30 minutes, for example, within approximately 15 minutes, for example, within approximately 10 minutes, for example, within approximately 5 minutes. In some embodiments, when placed in the user's mouth, the oral product releases at least 60% by weight of cannabinoids within a maximum of approximately 60 minutes, for example, within approximately 45 minutes, for example, within approximately 30 minutes, for example, within approximately 15 minutes, for example, within approximately 10 minutes, for example, within approximately 5 minutes. In some embodiments, when placed in the user's mouth, the oral product releases at least 70% by weight of cannabinoids within a maximum of approximately 60 minutes, for example, within approximately 45 minutes, for example, within approximately 30 minutes, for example, within approximately 15 minutes, for example, within approximately 10 minutes, for example, within approximately 5 minutes. In some embodiments, when placed in the user's mouth, the oral product releases at least 80% by weight of cannabinoids within a maximum of approximately 60 minutes, for example, within approximately 45 minutes, for example, within approximately 30 minutes, for example, within approximately 15 minutes, for example, within approximately 10 minutes, for example, within approximately 5 minutes. In some embodiments, when placed in the user's mouth, the oral product releases at least 90% by weight of cannabinoids within a maximum of approximately 60 minutes, for example, within approximately 45 minutes, for example, within approximately 30 minutes, for example, within approximately 15 minutes, for example, within approximately 10 minutes, for example, within approximately 5 minutes. In some embodiments, when placed in the user's mouth, the oral product releases at least 95% by weight of cannabinoids within a maximum of approximately 60 minutes, for example, within approximately 45 minutes, for example, within approximately 30 minutes, for example, within approximately 15 minutes, for example, within approximately 10 minutes, for example, within approximately 5 minutes.

[0224] The rate of release into the oral cavity can be measured using an in vitro dissolution test. The dissolution profile of cannabinoids can be measured as the amount of cannabinoid released after a certain period of time in 1 liter of phosphate buffer maintained at 37°C with a pH of approximately 7.4, using a USP paddle dissolution apparatus.

[0225] In some embodiments, at least 30% by weight of the released cannabinoids (i.e., those released into the user's oral cavity over a specified period) is absorbed into the oral mucosa within a maximum of about 60 minutes, for example, within about 45 minutes, for example, within about 30 minutes, for example, within about 15 minutes, for example, within about 10 minutes, for example, within about 5 minutes. In some embodiments, at least 40% by weight of the released cannabinoids (i.e., those released into the user's oral cavity over a specified period) is absorbed into the oral mucosa within a maximum of about 60 minutes, for example, within about 45 minutes, for example, within about 30 minutes, for example, within about 15 minutes, for example, within about 10 minutes, for example, within about 5 minutes. In some embodiments, at least 50% by weight of the released cannabinoids (i.e., those released into the user's oral cavity over a specified period) is absorbed into the oral mucosa within a maximum of about 60 minutes, for example, within about 45 minutes, for example, within about 30 minutes, for example, within about 15 minutes, for example, within about 10 minutes, for example, within about 5 minutes. In some embodiments, at least 60% by weight of the released cannabinoids (i.e., those released into the user's oral cavity over a specified period) is absorbed into the oral mucosa within a maximum of about 60 minutes, for example, within about 45 minutes, for example, within about 30 minutes, for example, within about 15 minutes, for example, within about 10 minutes, for example, within about 5 minutes. In some embodiments, at least 70% by weight of the released cannabinoids (i.e., those released into the user's oral cavity over a specified period) is absorbed into the oral mucosa within a maximum of about 60 minutes, for example, within about 45 minutes, for example, within about 30 minutes, for example, within about 15 minutes, for example, within about 10 minutes, for example, within about 5 minutes. In some embodiments, at least 75% by weight of the released cannabinoids (i.e., those released into the user's oral cavity over a specified period) is absorbed into the oral mucosa within a maximum of about 60 minutes, for example, within about 45 minutes, for example, within about 30 minutes, for example, within about 15 minutes, for example, within about 10 minutes, for example, within about 5 minutes.

[0226] In some embodiments, the oral product releases cannabinoids such that at least about 20% by weight of the cannabinoids is absorbed into the user's oral mucosa (e.g., gingiva or buccal mucosa) within a maximum of about 60 minutes, for example, a maximum of about 45 minutes, for example, a maximum of about 30 minutes, for example, a maximum of about 15 minutes, for example, a maximum of about 10 minutes, for example, a maximum of about 5 minutes. In some embodiments, the oral product releases cannabinoids such that at least about 25% by weight of the cannabinoids is absorbed into the user's oral mucosa within a maximum of about 60 minutes, for example, a maximum of about 45 minutes, for example, a maximum of about 30 minutes, for example, a maximum of about 15 minutes, for example, a maximum of about 10 minutes, for example, a maximum of about 5 minutes. In some embodiments, the oral product releases cannabinoids such that at least about 30% by weight of the cannabinoids is absorbed into the user's oral mucosa within a maximum of about 60 minutes, for example, within about 45 minutes, for example, within about 30 minutes, for example, within about 15 minutes, for example, within about 10 minutes, for example, within about 5 minutes. In some embodiments, the oral product releases cannabinoids such that at least about 40% by weight of the cannabinoids is absorbed into the user's oral mucosa within a maximum of about 60 minutes, for example, within about 45 minutes, for example, within about 30 minutes, for example, within about 15 minutes, for example, within about 10 minutes, for example, within about 5 minutes. In some embodiments, the oral product releases cannabinoids such that at least about 50% by weight of the cannabinoids is absorbed into the user's oral mucosa within a maximum of about 60 minutes, for example, within about 45 minutes, for example, within about 30 minutes, for example, within about 15 minutes, for example, within about 10 minutes, for example, within about 5 minutes.

[0227] The percentage of absorption can be measured in vitro. For example, the degree of absorption of cannabinoids into the oral mucosa can be measured via octanol-water partitioning. For instance, the product can be dissolved in saliva at approximately 37°C and then extracted using octanol as part of a liquid-liquid extraction process. Thus, the percentage of the active ingredient absorbed into the oral mucosa (i.e., the degree of in vitro absorption) corresponds to the percentage extracted into octanol.

[0228] The release characteristics and absorption rates of cannabinoids into the oral mucosa can be measured by any suitable means. For example, techniques known to those skilled in the art for measuring the release and absorption of nicotine can be used.

[0229] Surprisingly, it was also found that oral products containing emulsions can be chemically and physically stable for at least six months, for example, at 50% relative humidity. "Chemically and physically stable" is understood to mean that cannabinoids do not migrate from the product, so there is no significant loss of cannabinoids in the product due to migration (chemical stability), no visible changes are observed over the measurement period (physical stability), and the solubility profile remains unchanged.

[0230] It is desirable that the product have a shelf life that allows it to be stored for several days, several weeks, or several months. Therefore, in some embodiments, the oral product is configured such that its water activity is about 0.85 or less, for example, about 0.8 or less, for example, about 0.75 or less, for example, about 0.7 or less, for example, about 0.6 or less, for example, about 0.5 or less. The inventors have found that when the water activity of the oral product is reduced to less than 0.85, the oral product can be stored for several weeks or several months without showing significant microbiological growth.

[0231] As described herein, the "water activity" (aw) of an oral product is calculated by dividing the partial vapor pressure of water in the product by the partial vapor pressure of water under standard conditions. Water activity can be calculated using the following formula:

[0232]

number

[0233] Method for preparing an oral product As described herein, the oral product (a) forming a nanoemulsion by the method as defined above herein, and (b) treating the nanoemulsion to provide an oral product can be prepared using a method comprising.

[0234] In some embodiments, the step of (b) treating the emulsion to provide an oral product in solid form comprises combining the nanoemulsion with a filler. The filler may be as described above herein. For example, in some embodiments, the filler may be a cellulose material, such as microcrystalline cellulose. In some embodiments, the filler may be present in an amount of at least 50% by weight of the oral product.

[0235] In some embodiments, the method further comprises the step of (a)(i) combining a filler (such as a cellulose material, such as microcrystalline cellulose) with a salt, a sweetening agent and / or a flavoring agent. Next, in order to form the oral product, the emulsion may be combined with the product obtained from (a)(i) in (b).

[0236] The ways in which the various components of the composition are combined can vary. Thus, for example, the overall composition containing the powdery composition components can be relatively homogeneous in nature. The above components, which can be in liquid or dry solid form, can be mixed in a pretreatment before being mixed with the remaining components of the composition, or simply mixed together with all the other liquid or dry components. The various components of the composition can be contacted, combined, or mixed together using any mixing technique or apparatus known in the art. Any mixing method that closely contacts the composition components, for example, a mixing apparatus having a stirring blade or other structure that can be stirred, can be used. Examples of mixing apparatuses include casing drums, conditioning cylinders or drums, liquid spray apparatuses, conical blenders, ribbon blenders, Littleford Day mixers available as FKM130, FKM600, FKM1200, FKM2000 and FKM3000, Plough Share type mixer cylinders, Hobart mixers, and the like. Further, see, for example, the types of methodologies described in U.S. Patent Nos. 4,148,325 (Solomon et al.), 6,510,855 (Korte), and 6,834,654 (Williams), each of which is incorporated herein by reference. In some embodiments, the components forming the composition are prepared such that a mixture of these components can be used in a shaping process for forming the composition. The manners and methods for formulating the composition will be apparent to those skilled in the art. See, for example, the types of methodologies described in U.S. Patent Nos. 4,148,325 (Solomon et al.), 6,510,855 (Korte et al.), 6,834,654 (Williams et al.), 4,725,440 (Ridgway et al.), 6,077,524 (Bolder et al.), each of which is incorporated herein by reference.

Example

[0237] Aspects of the present invention are more fully illustrated by the following examples. These examples are provided to illustrate specific aspects of the present disclosure and should not be construed as limiting the present invention.

[0238] [Example 1] Preparation of nanoemulsions The method according to the embodiments of this disclosure can be used to prepare an emulsion containing an oil phase, an aqueous phase, and a cannabinoid as an active ingredient.

[0239] The emulsion is prepared by mixing castor oil with cannabidiol isolate in a 3:1 weight ratio to prepare the oil phase. The mixture is heated at approximately 70°C for approximately 10 minutes until it becomes clear.

[0240] The aqueous phase is formed by mixing water with a preservative (sodium benzoate) and an emulsifier (a combination of Myrj 52 and lecithin). The amount of preservative is 0.4% by weight of the aqueous phase, and the amount of emulsifier is 20% by weight of the aqueous phase. Glycerin is also added to the water in an amount of 35% by weight of the aqueous phase. The components of the aqueous phase are subjected to high-shear mixing for 20 minutes. A high-shear mixer is used for the initial emulsion before the ultrasonic homogenization step. An IKA ULTRA-TURRAX disperser is used to prepare a homogeneous slurry of the solid components in water, and then to produce the initial emulsion. Typically, a shear rate of 5000-15000 rpm is required to prepare the aqueous slurry and the initial emulsion.

[0241] Next, the oil phase and the aqueous phase are combined in a weight ratio of 1:9 to provide a mixture containing the following components.

[0242] [Table 1]

[0243] The oil phase and aqueous phase are combined by high-shear mixing at 30°C for approximately 20 minutes or until a homogeneous, opaque emulsion is formed.

[0244] Next, the obtained macroemulsion is added to the supply vat of the ultrasonic probe homogenizer (i.e., ultrasonic generator) and the temperature is set to 30°C. The macroemulsion is flowed through the ultrasonic generator at 150 mL / min using an instrument-specific amplitude of 80 μm. The temperature exiting the ultrasonic generator should not exceed 40°C. A Fisherbrand Model 505 ultrasonic homogenizer with a maximum output of 500 watts is used for current batch preparation. A Hielscher UIP4000hdT ultrasonic homogenizer is used for large-scale batch production. Typical operating parameters for the Hielscher ultrasonic homogenizer are 15 liters / hour (flow rate), 21-66°C (temperature range), and 7 hours (operating time per day). Parameters may be adjusted during production to optimize product output and quality.

[0245] Next, the resulting nanoemulsion is passed through a filter (1 μm) system. Then, the resulting micelle droplet size is determined using a Malvern 3000 or equivalent instrument.

[0246] Preparation of oral products Next, prepare the oral product using the following method.

[0247] 1. Mix microcrystalline cellulose, sodium chloride, and acesulfame K as dry ingredients in a paddle blender.

[0248] 2. Next, spray the flavoring agent onto the dried components and mix until uniform.

[0249] 3. Next, spray the emulsion prepared above onto the resulting mixture and mix until uniform.

[0250] The resulting oral product has the following components:

[0251] [Table 2]

[0252] Oral products have desirable release and absorption characteristics when placed in the user's oral cavity.

[0253] The various embodiments described herein are presented solely to aid in understanding and teaching the features described in the claims. These embodiments are provided only as representative examples of the embodiments and are not exhaustive and / or exclusive. It should be understood that the advantages, embodiments, examples, functions, features, structures and / or other aspects described herein should not be considered as limitations on the scope of the invention as defined by the claims or limitations on equivalents of the claims, and that other embodiments may be utilized and modified without departing from the scope of the claimed invention. Various embodiments of the invention may preferably include, consist of, or essentially consist of, appropriate combinations of disclosed elements, components, features, parts, processes, means, etc., other than those specifically described herein. Furthermore, this disclosure may include other inventions that are not currently described in the claims but may be described in the claims in the future.

Claims

1. A method for preparing a nanoemulsion comprising a continuous phase and a dispersed phase, wherein the nanoemulsion comprises at least one cannabinoid and 5% to 25% by weight of an emulsifier based on the total weight of the nanoemulsion, the emulsifier being a combination of polyoxyethylene stearate and lecithin, the dispersed phase being an oil phase and comprising at least one cannabinoid and 5% to 30% by weight of oil based on the total weight of the nanoemulsion, the continuous phase being an aqueous phase comprising 20% ​​to 50% by weight of water and 20% to 40% by weight of a wetting agent based on the total weight of the nanoemulsion, the water-to-cannabinoid weight ratio being 10:1 to 1:

1. (a) A step of providing an oil phase containing at least one cannabinoid, (b) A step of providing an aqueous phase, a wetting agent, and an emulsifier. (c) A step of forming a macroemulsion by combining an oil phase, an aqueous phase, a wetting agent, and an emulsifier. (d) A process of processing a macroemulsion to form a nanoemulsion. including, method.

2. The method according to claim 1, wherein (d) is a step of ultrasonically treating a macroemulsion to form a nanoemulsion.

3. The method according to claim 1 or 2, wherein (d) is a step of processing a macroemulsion in a homogenizer to form a nanoemulsion.

4. The method according to claim 3, wherein the homogenizer is a high-pressure valve homogenizer, an ultrasonic jet homogenizer, or an ultrasonic probe homogenizer.

5. The method according to claim 3 or 4, wherein the macroemulsion passes through the homogenizer at a flow rate of approximately 100 mL / min to approximately 9 L / min.

6. The method according to any one of claims 3 to 5, wherein the macroemulsion passes through a homogenizer at a temperature of about 20°C to about 40°C.

7. The method according to claim 1, wherein (d) is a step of processing a macroemulsion in a microfluidizer to form a nanoemulsion.

8. The method according to any one of claims 1 to 7, further comprising the step of (a) (1) heating the oil phase to a temperature of at least about 50°C and dissolving at least one cannabinoid in the oil phase.

9. (a) The method according to claim 8, wherein (1) includes the step of heating the oil phase to a temperature of about 60°C to about 85°C.

10. (b) The method according to claim 1, wherein (1) includes a step of combining the aqueous phase with an emulsifier by high-shear mixing.

11. The method according to any one of claims 1 to 10, wherein (c) is a step of combining an oil phase and an aqueous phase by high shear mixing to form a macroemulsion.

12. The method according to any one of claims 1 to 11, wherein (c) is a step of combining an oil phase and an aqueous phase in a weight ratio of about 2:1 to about 1:

10.

13. The method according to any one of claims 1 to 12, wherein 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), cannabiclomevalin (CBCV), cannabigerovalin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerol acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivaric acid (THCV A), and mixtures thereof.

14. The method according to any one of claims 1 to 13, wherein the cannabinoid comprises cannabidiol.

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