Cannabinoid emulsion
Patent Information
- Authority / Receiving Office
- EP · EP
- Patent Type
- Applications
- Current Assignee / Owner
- BLACK & BLUE FOODS INC
- Filing Date
- 2024-08-09
- Publication Date
- 2026-06-17
AI Technical Summary
Existing emulsions for cannabinoid delivery face challenges such as limited stability, bioavailability issues, and content uniformity, particularly in aqueous-based products like beverages.
A stable emulsion comprising cannabinoid compounds, optionally terpenes, and a complex of whey protein and casein protein, which provides a healthy and high-concentration formulation for oral consumption.
The emulsion maintains stability at room and high temperatures, ensuring effective bioavailability and uniform distribution of cannabinoids, making it suitable for various consumer products including beverages and natural health supplements.
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Figure CA2024051049_13022025_PF_FP_ABST
Abstract
Description
CANNABINOID EMULSIONCROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims the benefit of priority from co-pending U.S. Provisional Patent Application No. 63 / 531 ,864 filed August 10, 2023, the contents of which are incorporated herein by reference in their entirety.FIELD
[0002] The present application relates to emulsions comprising cannabinoid or cannabis derived compounds and optionally terpenes, and methods of preparation thereof. Further, the present application relates to compositions comprising the emulsion, and uses thereof.BACKGROUND
[0003] Cannabinoids are a class of diverse chemical compounds that act on cannabinoid receptors in cells that alter neurotransmitter release in the brain. So far, over a hundred cannabinoids have been identified from cannabis, for example tetrahydrocannabinol (THC), cannabidiol (CBD). Cannabinoids have been shown to possess anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties, and it is thus important to develop suitable optimized delivery systems in which cannabinoids will achieve a therapeutically effective dose.
[0004] Oral and inhaled are the most common and convenient routes of administration for the cannabinoids, for example by inhaling cigarettes or taking capsules, foods or liquids. However, cannabinoids are hydrophobic compounds and are insoluble in water, which presents challenges in making products for oral consumption with effective bioavailability of cannabinoids at defined finished product concentrations.
[0005] Emulsions carry lipophilic compounds into suspended small oil droplets which makes them dispersible in aqueous phases. Nevertheless, the limited stability of emulsions remains a practical application issue, which means that with time they will undergo coalescence, creaming, sedimentation, Ostwald ripening and finally separation into their two original liquid phases due to free energy. This represents a big challenge for making products for oral consumption. Thus, careful consideration of components and methods of emulsification is needed to provide a stable emulsion. Inaddition, healthy components of the emulsion appropriate for oral administration are highly desirable.
[0006] The complex chemistry and limited physical stability of emulsions in aqueous suspensions may lead to content uniformity issues. It is desired that concentrations of cannabinoids and other nutritional additives remain uniformly distributed and suspended in the final product.
[0007] US 10,143,212 patent discloses an emulsion, in which the lipid is encapsulated by a complex of casein and whey protein. However, this patent does not disclose an emulsion with cannabinoids, cannabis-derived compounds, terpenes or combinations thereof.
[0008] A need therefore exists for improved water-soluble formulations of cannabinoids that may be used in the preparation of consumer products such as cannabis edibles, food supplements and natural health products (NHP), and in particular aqueous-based products such as beverages.SUMMARY
[0009] The present application discloses an emulsion comprising cannabinoid compounds, optionally terpenes and casein and whey proteins. The emulsion is stable at room temperature and at high temperature processing and provides a healthy and high concentration formulation of cannabinoid compounds that may be used to prepare, for example, liquid or powder compositions. The liquid compositions may be used to prepare, for example, beverages. The compositions of the application can be used, for example, in supplements and natural health products that improve the overall health of a subject which reduces the incidence and / or severity of diseases, disorders or conditions, for example by supporting the subject’s body’s own ability to reduce pain and / or inflammation.
[0010] Accordingly, present application includes an emulsion comprising: a) one or more cannabinoid compounds; b) a complex of whey protein and casein protein; c) water; and d) an oil.
[0011] In some embodiments, the one or more cannabinoid compounds are selected from cannabigerolic acid (CBGA), cannabigerolic acid monomethylether (CBGAM), cannabigerol (CBG), cannabigerol monomethylether (CBGM), cannabigerovarinic acid (CBGVA), cannabigerovarin (CBGV), cannabichromenic Acid (CBCA), cannabichromene (CBC), cannabichromevarinic acid (CBCVA), cannabichromevarin (CBCV), cannabidiolic acid (CBDA), cannabidiol (CBD), A6 cannabidiol (A6-CBD), cannabidiol monomethylether (CBDM), cannabidiol-C4 (CBD C4), cannabidivarinic acid (CBDVA), cannabidivarin (CBDV), cannabidiorcol (CBD C1), tetrahydrocannabinolic acid A (THCA-A), tetrahydrocannabinolic acid B (THCA- B), tetrahydrocannabinol (THC or A9-THC), A8-tetrahydrocannabinol (A8-THC), A10- tetrahydrocannabinol (A10-THC), tetrahydrocannabinolic acid C4 (THCA-C4), tetrahydrocannbinol C4 (THC C4), tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabivarin (THCV), A8-tetrahydrocannabivarin (A8-THCV), A9 tetrahydrocannabivarin (A9-THCV), tetrahydrocannabiorcolic acid (THCA-C1), tetrahydrocannabiorcol (THC-C1), delta 7 cis iso tetrahydrocannabivarin, A8 tetrahydrocannabinolic acid (A8-THCA), A9 tetrahydrocannabinolic acid (A9-THCA), cannabicyclolic acid (CBLA), cannabicyclol (CBL), cannabicyclovarin (CBLV), cannabielsoic acid A (CBEA-A), cannabielsoic acid B (CBEA-B), cannabielsoin (CBE), cannabinolic acid (CBNA), cannabinol (CBN), cannabinol methylether (CBNM), cannabinol-C4 (CBN-C4), cannabivarin (CBV), cannabino-C2 (CBN-C2), cannabiorcol (CBN-C1), cannabinodiol (CBND), cannabinodivarin (CBDV), cannabitriol (CBT), 11 hydroxy-A9-tetrahydrocannabinol (11 OH-THC), 11 nor 9-carboxy-A9- tetrahydrocannabinol ethoxy-cannabitriolvarin (CBTVE), 10 ethoxy-9-hydroxy-A6a- tetrahydrocannabinol, cannabitriolvarin (CBTV), 8,9 dihydroxy-A6a(10a)- tetrahydrocannabinol (8,9-Di-OH-CBT-C5), dehydrocannabifuran (DCBF), cannbifuran (CBF), cannabichromanon (CBCN), cannabicitran (CBT), 10 oxo- A6a(10a)-tetrahydrocannabinol (OTHC), A9-cis-tetrahydrocannabinol (cis-THC), cannabiripsol (CBR), 3,4,5,6-tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n- propyl-2,6-methano-2H-1-benzoxocin-5-methanol (OH-iso-HHCV), and trihydroxy- delta-9-tetrahydrocannabinol (triOH-THC), or any combination thereof.
[0012] In some embodiments, the emulsion further comprises one or more terpenes and / or one or more terpenoids.
[0013] In some embodiments, the oil is omega-3 oil. In some embodiments, the omega-3 oil is selected from oils obtained from fish such as salmon, tuna, herring, mackerel, anchovies, sardines, pollock, cod, catfish, flounder, grouper, halibut, mahi mahi, orange roughy, red snapper, shark, swordfish, tilefish, plankton, algae, krill and / or green-lipped mussel, and / or plant oils such as canola oil, borage oil, evening primrose oil, safflower oil, sunflower oil, flaxseed oil, wheat germ oil, algal oil, or and grapeseed oil, and oils obtained from chia seeds, kiwifruit seeds, perilla seeds, lingonberry seeds, camelina seeds, purslane seeds, black raspberry seeds, hemp seeds, butternut, walnuts, pecan nuts, and / or hazel nuts.
[0014] The present application includes a powder formulation which comprises the emulsion of the present application.
[0015] The present application includes a use of the emulsion of the present application in compositions selected from beverages, gels, gelatins and concentrates and a use as a beverage enhancer.
[0016] The present application includes a composition selected from a beverage, gel, gelatin, concentrate and beverage enhancer, wherein the composition comprises the emulsion of the present application.
[0017] The present application includes a method of reducing the incidence and / or severity of a disease, disorder or condition, the method comprising administering a composition of the present application to a subject in need thereof.
[0018] The present application also includes a method of improving resistance to a disease, disorder or condition and / or improving immune response, the method comprising administering a composition of the present application to a subject in need thereof. In some embodiments, the disease, disorder or condition is joint pain, inflammatory pain and / or osteoarthritic pain.
[0019] Th present application also includes a method of preparing the emulsion, the dry formulation and the liquid composition of the present application.
[0020] Other features and advantages of the present application will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating embodiments of the application, are given by way of illustration only and the scope of the claimsshould not be limited by these embodiments but should be given the broadest interpretation consistent with the description as a whole.DRAWINGS
[0021] The embodiments of the application will now be described in greater detail with reference to the attached drawings in which:
[0022] Figure 1 shows the change of particle size (nm) over time (days) of initial batch Lot LC-NPMC-2022-04-18-1-B&B, an exemplary composition of the application. The lines as seen at the y-axis at time 0 are as follows: 3000 psi, 1st pass; 6000 psi, 1 st pass; 10000 psi, 2nd pass; and 3000 psi, 2nd pass.
[0023] Figure 2 shows the change in particle size (nm) over time (days) of the experimental batch Lot LC-NPMC-2022-04-29-1-B&B, exemplary compositions of the application. The lines as seen at the y-axis at time 0 are as follows: 5000 psi, 3rd pass; 5000 psi, 2nd pass; 5000 psi, 5th pass; 3000 psi, 5th pass; and 3000 psi, 3rd pass.
[0024] Figure 3 shows the parameter effect chart for particle size for exemplary compositions of the application.
[0025] Figure 4 shows the parameter effect chart for zeta potential for exemplary compositions of the application.
[0026] Figure 5 shows the parameter effect chart for change in particle size for exemplary compositions of the application.
[0027] Figure 6 shows the parameter effect chart for change in zeta potential for exemplary compositions of the application.
[0028] Figure 7 shows the parameter effect chart for change in pH for exemplary compositions of the application.
[0029] Figure 8 shows the high-performance liquid chromatography (HPLC) chromatogram of negative control sample.
[0030] Figure 9 shows particle size of exemplary emulsions stored for four weeks at 25 °C and 4 °C (top line refers to 25 °C showing a particle size of 978.7 after 4 weeks of storage and bottom line refers to 4 °C showing a particle size of 878.8 after 4 weeks of storage).
[0031] Figure 10 shows zeta potential of exemplary emulsions stored for four weeks at 25 °C and 4 °C (after one week of storage, top line refers to 4 °C showing a zeta potential of 33.4 and bottom line refers to 25 °C showing a zeta potential of 32.3).
[0032] Other features and advantages of the present disclosure will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating embodiments of the disclosure, are given by way of illustration only and the scope of the claims should not be limited by these embodiments, but should be given the broadest interpretation consistent with the description as a whole.DESCRIPTION OF VARIOUS EMBODIMENTSI. Definitions
[0033] Unless otherwise indicated, the definitions and embodiments described in this and other sections are intended to be applicable to all embodiments and aspects of the present application herein described for which they are suitable as would be understood by a person skilled in the art.
[0034] All features disclosed in the specification, including the claims, abstract, and drawings, and all the steps in any method or process disclosed, may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. Each feature disclosed in the specification, including the claims, abstract, and drawings, can be replaced by alternative features serving the same, equivalent, or similar purpose, unless expressly stated otherwise.
[0035] As used in this application and claim(s), the words "comprising" (and any form of comprising, such as "comprise" and "comprises"), "having" (and any form of having, such as "have" and "has"), "including" (and any form of including, such as "include" and "includes") or "containing" (and any form of containing, such as "contain" and "contains"), are inclusive or open-ended and do not exclude additional, unrecited elements or process steps.
[0036] The term “consisting” and its derivatives as used herein are intended to be closed terms that specify the presence of the stated features, elements, components, groups, integers, and / or steps, and also exclude the presence of other unstated features, elements, components, groups, integers and / or steps.
[0037] The term “consisting essentially of”, as used herein, is intended to specify the presence of the stated features, elements, components, groups, integers, and / or steps as well as those that do not materially affect the basic and novel characteristic(s) of these features, elements, components, groups, integers, and / or steps.
[0038] The terms "about", “substantially” and “approximately” as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least ±5% of the modified term if this deviation would not negate the meaning of the word it modifies or unless the context suggests otherwise to a person skilled in the art.
[0039] As used in the present application, the singular forms “a”, “an” and “the” include plural references unless the content clearly dictates otherwise. For example, an embodiment including “a compound” should be understood to present certain aspects with one compound, or two or more additional compounds.
[0040] In embodiments comprising an “additional” or “second” component or effect, such as an additional or second compound, the second compound as used herein is different from the other compounds or first compound. A “third” compound is different from the other, first, and second compounds, and further enumerated or “additional” compounds are similarly different.
[0041] The term “and / or” as used herein means that the listed items are present, or used, individually or in combination. In effect, this term means that “at least one of” or “one or more” of the listed items is used or present. The term “and / or” with respect to enantiomers, prodrugs, salts and / or solvates thereof means that the compounds of the application exist as individual enantiomers, prodrugs, salts and hydrates, as well as a combination of, for example, a salt of a solvate of a compound of the application.
[0042] The term “cannabinoid” as used herein refers to a class of chemical compounds that act on cannabinoid receptors in cells that alter neurotransmitter release in the brain and other organs and tissues of the endocannabinoid and immune systems. Cannabinoids also include synthetic (made in a laboratory setting) and semisynthetic cannabinoids (derived or obtained from a natural source, e.g. plant, and issubsequently modified or derivatized in one or more different ways in a laboratory setting).
[0043] The term “distillate” as used herein refers to a purified cannabinoid obtained by a distillation of cannabis plant material, such as cannabis oil or cannabis extract. To produce the distillate, the cannabis plant material is distilled to remove noncannabinoid components such as lipids, waxes, carbohydrates, and others and the distillation can be performed by any method known in the art.
[0044] The term “isolate” as used herein refers to a product of a purification of cannabis plant material, such as cannabis oil and cannabis extract or cannabinoid distillate, to obtain purified cannabinoid. The purification, in which non-cannabinoid components such as lipids, waxes, carbohydrates, and others are removed, can be performed by any purification method known in the art.
[0045] The term “cannabis oil” as used herein refers to an oil extracted from a plant of the Cannabis genus and contains one or more cannabinoids.
[0046] The term “cannabis extract” as used herein refers to material extracted from a plant of the Cannabis genus and contains one or more cannabinoids.
[0047] The term “cannabigerol” or “CBG” as used herein refers to a cannabinoid found in the Cannabis genus of plants or synthetic or semi-synthetic analogue thereof. CBG has the following chemical structure:
[0048] The term “cannabidiol” or “CBD” as used herein refers to a cannabinoid found in the Cannabis genus of plants or synthetic or semi-synthetic analogue thereof. CBD has the following chemical structure:
[0049] The term “tetrahydrocannabinol” or “THC” as used herein refers to a cannabinoid ((-)-trans-A9-tetrahydrocannabinol) found in the Cannabis genus of plants or synthetic or semi-synthetic analogue thereof. THC has the following chemical structure:
[0050] The term “terpene” and “terpenoids” as used herein refers to cannabis derived terpenes / terpenoids and non-cannabis derived terpenes. Terpenes are hydrocarbons, whereas terpenoids contain additional functional groups.
[0051] The term “flavonoid” as used herein refers to any compound of a class of plant pigments having a structure based on or similar to that of flavone. Chemically, flavonoids have the general structure of a 15-carbon skeleton, which consists of two phenyl rings and a heterocyclic ring.
[0052] The term “aqueous solution” as used herein refer to a water-based solution.
[0053] The term “neutraceutical” or “nutraceutical” as used herein is a combination of the terms “nutritional” and “pharmaceutical”. It refers to a composition, which is known or suspected in the art to positively affect human nutrition and / or health. Nutraceuticals include nutritional supplements and natural health products (NHP), which may or may not have regulatory approval.
[0054] The term "emulsion" as used herein refers to a colloidal dispersion of two immiscible liquids, for example, an oil and water, one of which is part of a continuous phase and the other of which is part of a dispersed phase.
[0055] The term “omega-3 fatty acid” as used herein means a polyunsaturated fatty acid whose first double bond occurs at the third carbon-carbon bond from the end opposite the acid group.
[0056] The term “omega-3 oil” as used herein means oil that contains at least one (e.g., one, two, or three) fatty acid(s) containing a carbon-carbon double bond in the n-3 position (i.e. , the third bond from the methyl end of the fatty acid).
[0057] The term "particle size" as used herein refers to oil in water droplet average diameter in an emulsion.
[0058] The term "stable" as used herein refers the ability of the compound, composition or emulsion of the application to resist change in its chemical properties over time.
[0059] The term "subject" as used herein includes all members of the animal kingdom including mammals, and suitably refers to humans.
[0060] The term “treating” or “treatment” as used herein and as is well understood in the art, means an approach for obtaining beneficial or desired results, including clinical results. Beneficial or desired results include, but are not limited to alleviation or amelioration of one or more symptoms or conditions, diminishment of extent of one or more symptoms or conditions, stabilized (i.e. not worsening) state of one or more symptoms or conditions, preventing spread of one or more symptoms or conditions, diminishment of the reoccurrence of one or more symptoms or conditions (whether partial or total), whether detectable or undetectable. “Treating” and “treatment” as used herein also include prophylactic treatment. Treatment methods comprise administering to a subject an effective amount of one or more of the emulsions or compositions of the present application and optionally consist of a single administration, or alternatively comprise a series of administrations.
[0061] As used herein, the term “effective amount” or “therapeutically effective amount” means an amount of an emulsion or a composition of the application that is effective, at dosages and for periods of time necessary to achieve the desired result.
[0062] The term “administered” as used herein means administration of a therapeutically effective amount of an emulsion of the application or a composition of the application to a subject.
[0063] The term “emulsion of the application” refers to the emulsion as described herein.
[0064] The term “composition of the application” refers to the compositions comprising the emulsion of the application.
[0065] The term “powder formulation” refers to a powder obtained by drying the emulsion of the application.
[0066] Unless otherwise indicated the term “wt%” as used herein refers to wt / wt%.II. Emulsions of the Application
[0067] The present application includes an emulsion comprising: a) one or more cannabinoid compounds; b) a complex of whey protein and casein protein; c) water; and d) an oil.
[0068] In some embodiments, the one or more cannabinoid compounds are selected from cannabigerolic acid (CBGA), cannabigerolic acid monomethylether (CBGAM), cannabigerol (CBG), cannabigerol monomethylether (CBGM), cannabigerovarinic acid (CBGVA), cannabigerovarin (CBGV), cannabichromenic Acid (CBCA), cannabichromene (CBC), cannabichromevarinic acid (CBCVA), cannabichromevarin (CBCV), cannabidiolic acid (CBDA), cannabidiol (CBD), A6 cannabidiol (A6-CBD), cannabidiol monomethylether (CBDM), cannabidiol-C4 (CBD C4), cannabidivarinic acid (CBDVA), cannabidivarin (CBDV), cannabidiorcol (CBD C1), tetrahydrocannabinolic acid A (THCA-A), tetrahydrocannabinolic acid B (THCA- B), tetrahydrocannabinol (THC or A9-THC), A8-tetrahydrocannabinol (A8-THC), A10- tetrahydrocannabinol (A10-THC), tetrahydrocannabinolic acid C4 (THCA-C4), tetrahydrocannbinol C4 (THC C4), tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabivarin (THCV), A8-tetrahydrocannabivarin (A8-THCV), A9tetrahydrocannabivarin (A9-THCV), tetrahydrocannabiorcolic acid (THCA-C1), tetrahydrocannabiorcol (THC-C1), delta 7 cis iso tetrahydrocannabivarin, A8 tetrahydrocannabinolic acid (A8-THCA), A9 tetrahydrocannabinolic acid (A9-THCA), cannabicyclolic acid (CBLA), cannabicyclol (CBL), cannabicyclovarin (CBLV), cannabielsoic acid A (CBEA-A), cannabielsoic acid B (CBEA-B), cannabielsoin (CBE), cannabinolic acid (CBNA), cannabinol (CBN), cannabinol methylether (CBNM), cannabinol-C4 (CBN-C4), cannabivarin (CBV), cannabino-C2 (CBN-C2), cannabiorcol (CBN-C1), cannabinodiol (CBND), cannabinodivarin (CBDV), cannabitriol (CBT), 11 hydroxy-A9-tetrahydrocannabinol (11 OH-THC), 11 nor 9-carboxy-A9- tetrahydrocannabinol ethoxy-cannabitriolvarin (CBTVE), 10 ethoxy-9-hydroxy-A6a- tetrahydrocannabinol, cannabitriolvarin (CBTV), 8,9 dihydroxy-A6a(10a)- tetrahydrocannabinol (8,9-Di-OH-CBT-C5), dehydrocannabifuran (DCBF), cannbifuran (CBF), cannabichromanon (CBCN), cannabicitran (CBT), 10 oxo- A6a(10a)-tetrahydrocannabinol (OTHC), A9-cis-tetrahydrocannabinol (cis-THC), cannabiripsol (CBR), 3,4,5,6-tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n- propyl-2,6-methano-2H-1-benzoxocin-5-methanol (OH-iso-HHCV), and trihydroxy- delta-9-tetrahydrocannabinol (triOH-THC), or any combination thereof.
[0069] In some embodiments, the one or more cannabinoid compounds are a salt, isomer, enantiomer, or optically active derivative thereof. In some embodiments, the one or more cannabinoid compounds are derived from a natural source. In some embodiments, the one or more cannabinoid compounds are derived from a plant of the Cannabis genus, e.g., Cannabis sativa, Cannabis indica, Cannabis hybrid, or other genera. In some embodiments, the one or more cannabinoid compounds are synthetic or semi-synthetic cannabinoids.
[0070] In some embodiments, the one or more cannabinoid compounds are comprised in a distillate, an isolate, cannabis oil, cannabis extract or a combination thereof. In some embodiments, the one or more cannabinoid compounds are comprised in a distillate. In some embodiments, the one or more cannabinoid compounds are comprised in an isolate. In some embodiments, the one or more cannabinoid compounds are comprised in a cannabis oil. In some embodiments, the one or more cannabinoid compounds are comprised in a cannabis extract.
[0071] In some embodiments, the distillate is obtained from cannabis extract or cannabis oil. In some embodiments, the cannabis extract or cannabis oil are distilledto obtain the distillate. In some embodiments, the distillate comprises from about 70 wt% to about 95 wt %, from about 75 wt% to about 90 wt%, from about 80 wt% to about 95 wt %, from about 85 wt% to about 95 wt % of one or more cannabinoid compounds. In some embodiments, the distillate comprises about 85, 86, 87, 88, 89, 90, 91 , 92 or 93 wt% of one or more cannabinoid compounds, and values therebetween.
[0072] In some embodiments, the isolate comprises from about 95 wt% to about 100 wt%, about 97 wt% to about 100 wt%, or about 98 wt% to about 100 wt % of one or more cannabinoid compounds, and values therebetween.
[0073] In some embodiments, the cannabis oil containing one or more cannabinoid compounds is extracted from a plant of the Cannabis genus, e.g., Cannabis sativa, Cannabis indica, Cannabis hybrid, or other genera, using various techniques known in the art, such as solvent-based extraction.
[0074] In some embodiments, the cannabis extract containing one or more cannabinoid compounds is extracted from a plant of the Cannabis genus, e.g., Cannabis sativa, Cannabis indica, Cannabis hybrid, or other genera, using any suitable technique for separating cannabinoids from the plant. In some embodiments, the extract can be obtained using solvent-based extraction.
[0075] In some embodiments, the one or more cannabinoid compounds is or comprises CBG, or a salt, isomer, enantiomer, or optically active derivative thereof. In some embodiments, the one or more cannabinoid compounds is or is comprised in a CBG distillate. In some embodiments, the one or more cannabinoid compounds is or is comprised in a CBG isolate.
[0076] In some embodiments, the one or more cannabinoid compounds is or comprises CBD, or a salt, isomer, enantiomer, or optically active derivative thereof. In some embodiments, the one or more cannabinoid compounds is or is comprised in a CBD distillate. In some embodiments, the one or more cannabinoid compounds is or is comprised in a CBD isolate.
[0077] In some embodiments, the one or more cannabinoid compounds is or comprises THC, or a salt, isomer, enantiomer, or optically active derivative thereof. In some embodiments, the one or more cannabinoid compounds is or is comprised in aTHC distillate. In some embodiments, the one or more cannabinoid compounds is or is comprised in a THC isolate.
[0078] In some embodiments, the emulsion of the application comprises one cannabinoid (single cannabinoid). In some embodiments, the emulsion of the application comprises two or more cannabinoid compounds. In some embodiments, the emulsion of the application comprises two, three, four or more cannabinoid compounds. In some embodiments, the emulsion of the application comprises two cannabinoid compounds. In some embodiments, the emulsion of the application comprises two or more cannabinoid compounds comprised in a distillate, an isolate, cannabis oil, cannabis extract or a combination thereof.
[0079] In some embodiments, the one or more cannabinoid compounds are present in the emulsion in an amount of about 0.25 wt% to about 13 wt% of the emulsion. In some embodiments, the one or more cannabinoid compounds are present in the emulsion in an amount of about 0.25 wt%, about 0.5 wt%, about 1 wt%, about 1 .5 wt%, about 2 wt%, about 4 wt%, about 5 wt%, about 7 wt%, about 8.5 wt% or about 10 wt% and values therebetween. In some embodiments, the one or more cannabinoid compounds are present in the emulsion in an amount of about 0.5 wt%. In some embodiments, the one or more cannabinoid compounds are present in the emulsion in an amount of about 1.2 wt%. In some embodiments, the one or more cannabinoid compounds are present in the emulsion at in an amount of about 2.4 wt%. In some embodiments, the one or more cannabinoid compounds are present in the emulsion in an amount of about 5.1 wt%. In some embodiments, the one or more cannabinoid compounds are present in the emulsion in an amount of about 10.2 wt%.
[0080] In some embodiments, the emulsion further comprises one or more terpenes, one or more terpenoids, one or more flavonoids, and any combinations thereof. In some embodiments, the emulsion further comprises one or more terpenes and / or one or more terpenoids. In some embodiments, the one or more terpenes and / or one or more terpenoids are selected from abietane, alpha-bisabolol, alphaphellandrene, alpha-pinene, beta-caryophyllene, beta-myrcene, beta-pinene, borneol, cadinene, camphene, camphor, carvacrol, caryophyllene acetate, caryophyllene oxide, cedrane, cembrene, citral, citronellol, copaene, dextro carvone, dextro fenchone, eucalyptol, eugenol, farnesene, gama-3-carene, gamma-terpinene, geraniol, geranyl acetate, guaiazulene, guaiene, humulene, isopulegol, labdane,limonene, linalool, longifolene, menthol, nerol, nerolidol, ocimene, ocimene, patchoulol, p-cymene, phytane, phytol, pinene, pulegone, retinal, retinol, sclarene, stemarene, stemoden, terpineol, terpinolele, terpinolene, texadiene, thymol, valencene, valencene, vetivazulene, and zingiberene, or any combination thereof, or a salt, isomer, enantiomer, or optically active derivative thereof. In some embodiments, the one or more terpenes and / or one or more terpenoids comprise hemiterpenes, monoterpenols, terpene esters, diterpenes, monoterpenes, polyterpenes, tetraterpenes, terpenoid oxides, sesterterpenes, sesquiterpenes, norisoprenoids, or their derivatives, as well as isomeric, enantiomeric, or optically active derivatives thereof. In some embodiments, the derivatives of the one or more terpenes and / or one or more terpenoids comprise terpenoids, hemiterpenoids, monoterpenoids, sesquiterpenoids, sesterterpenoid, sesquarterpenoids, tetraterpenoids, triterpenoids, tetraterpenoids, polyterpenoids, isoprenoids, or steroids. In some embodiments, the one or more terpenes and / or one or more terpenoids comprise a-(alpha), p-(beta), y- (gamma), oxo-, isomers, or any combinations thereof.
[0081] In some embodiments, the emulsion further comprises one or more flavonoids selected from bioflavonoids, isoflavonoids and neoflavonoids. In some embodiments, the one or more flavonoids are present in the emulsion in an amount of from about 0.00001 wt% to about 0.01 wt%.
[0082] In some embodiments, the one or more terpenes and / or one or more terpenoids are present in the emulsion in an amount of about 0 wt% to about 13 wt% of the emulsion. In some embodiments, the one or more terpenes and / or one or more terpenoids are present in the emulsion in an amount of about 0 to about 0.1 wt%, about 0 to about 0.5 wt%, about 0.5 to about 1 wt%, about 0 to about 1 wt%, about 0 to about 5 wt%, about 0 to about 12 wt%, about 1 to about 2 wt%, about 2 to about 3 wt%, about 3 to about 4 wt%, about 4 to about 5 wt%, about 5 to about 7.5 wt%, about 5 to about 10 wt% or about 10 to about 12.5 wt%, and values therebetween.
[0083] In some embodiments, the whey protein used in the emulsion of the application is any milk serum protein or protein composition known in the art, including, but not limited to, protein isolate, whey protein concentrate, a-lactalbumin and / or p- lacoglobulin. In some embodiments, the whey protein is selected from whey protein isolate, whey protein concentrate, a-lactalbumin and p-lacoglobulin. In some embodiments, the whey protein is whey protein isolate.
[0084] In some embodiments, the casein protein used in the emulsion of the application is any casein protein known in the art. In some embodiments, the casein protein is selected from a-casein, K-casein, p-casein, b-casein, and their salts, such as sodium, potassium, calcium and ammonium, or mixtures thereof. In some embodiments, the casein protein is sodium caseinate.
[0085] In some embodiments, the whey protein is present in the emulsion in an amount of about 0.25 wt% to about 5 wt% of the emulsion. In some embodiments, the whey protein is present in the emulsion in an amount of about 0.5 wt%, about 1 wt%, about 1 .25 wt%, about 1 .5 wt%, about 1 .8 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt% or about 5 wt% and values therebetween. In some embodiments, the whey protein is present in the emulsion in an amount of about 0.5 wt%. In some embodiments, the whey protein is present in the emulsion in an amount of about 1 .3 wt%. In some embodiments, the casein protein is present in the emulsion in an amount of about 3 wt%.
[0086] In some embodiments, the casein protein is present in the emulsion in an amount of about 0.25 wt% to about 5 wt% of the emulsion. In some embodiments, the casein protein is present in the emulsion in an amount of about 0.5 wt%, about 1 wt%, about 1.25 wt%, about 1.5 wt%, about 1.8 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt% or about 5 wt% and values therebetween. In some embodiments, the casein protein is present in the emulsion in an amount of about 0.5 wt%. In some embodiments, the casein protein is present in the emulsion in an amount of about 1 .3 wt%. In some embodiments, the casein protein is present in the emulsion in an amount of about 3 wt%.
[0087] In some embodiments, the weight ratio of casein protein to whey protein is about 10:1 to about 1 :10. In some embodiments, the weight ratio of casein protein to whey protein is about 6:1 to about 1 :6, about 3:1 to about 1 :3, about 2:1 to about 1 :2 or about 1 :1. In some embodiments, the weight ratio of casein protein to whey protein is about 6:1 to about 1 :6. In some embodiments, the weight ratio of casein protein to whey protein is 1 :1 .
[0088] In some embodiments, the whey protein is present in the emulsion in an amount of about 1.3 wt% and the casein protein is present in the emulsion in an amount of about 1 .3 wt%.
[0089] In some embodiments, the complex comprises whey protein and casein protein which are cross-linked or covalently bonded. In some embodiments, the one or more cannabinoid compounds are encapsulated in the complex of whey protein and casein protein.
[0090] In some embodiments, the water is present in the emulsion of the application in an amount of about 65 wt% to about 80 wt% of the emulsion. In some embodiments, the water is present in the emulsion of the application in an amount of about 68 wt%, about 70 wt%, about 73 wt%, about 75 wt%, or about 78 wt% and values therebetween.
[0091] In some embodiments, the whey protein and casein protein are dissolved in the water to form an aqueous solution and the emulsion is formed between the aqueous solution comprising the complex and the oil, and the one or more cannabinoid compounds are encapsulated by the complex of whey protein and casein protein.
[0092] In some embodiments, the oil which is used in the emulsion of the application includes any oil used in food, pharmaceutical or cosmetic industries. In some embodiments, the oil is an edible oil. In some embodiments, the oil is extracted from any appropriate source such as a marine animal, plant, phytoplankton or algae including microalgae, or is produced synthetically. The oil can be used in non-purified, purified or highly purified form, concentrated or non-concentrated. The oil aids in the dissolution of the cannabinoid or cannabis derived compound and allows for emulsification of the cannabinoid and cannabis-derived compounds.
[0093] In some embodiments, the oil is an omega-3 oil. In some embodiments, the oil contains omega-3 fatty acids or omega-3 fatty acid precursors such as a- linolenic acid. In some embodiments, the fatty acids that are present in the omega-3 oil are selected from one or more of all-cis-7,10,13-hexadecatrienoic acid; a-linolenic acid (ALA) (all-cis-9,12,15-octadecatrienoic acid); stearidonic acid (SDA) (all-cis- 6,9,12,15-octadecatetraenoic acid); eicosatrienoic acid (ETE) (all-cis- 11 ,14,17- eicosatrienoic acid); eicosatetraenoic acid (ETA) (all-cis-8,11 ,14,17-eicosatetraenoic acid); eicosapentaenoic acid (EPA) (all-cis-5,8,11 ,14,17-eicosapentaenoic acid); docosapentaenoic acid (DPA) (all-cis-7,10,13,16,19-docosapentaenoic acid); docosahexaenoic acid (DHA) (all-cis-4,7,10,13,16,19-docosahexaenoic acid);tetracosapentaenoic acid (all-cis-9,12,15,18,21-tetracosapentaenoic acid); and tetracosahexaenoic acid (nisinic acid) (all-cis-6,9, 12, 15,18,21 -tetracosahexaenoic acid). In some embodiments, the omega-3 fatty acids provide anti-inflammatory properties.
[0094] In some embodiments, the omega-3 is selected from oils obtained from fish such as salmon, tuna, herring, mackerel, anchovies, sardines, pollock, cod, catfish, flounder, grouper, halibut, mahi mahi, orange roughy, red snapper, shark, swordfish, tilefish, plankton, algae, krill and / or green-lipped mussel, and / or plant oils such as canola oil, borage oil, evening primrose oil, safflower oil, sunflower oil, flaxseed oil, wheat germ oil, algal oil, and / or grapeseed oil, and / or oils obtained from chia seeds, kiwifruit seeds, peri Ila seeds, lingonberry seeds, camelina seeds, purslane seeds, black raspberry seeds, hemp seeds, butternut, walnuts, pecan nuts, and / or hazel nuts. In some embodiments, the oil is sunflower oil. In some embodiments, the oil is algal oil.
[0095] In some embodiments, the oil is present in the emulsion of the application in an amount of about 8 wt% to about 30 wt% of the emulsion. In some embodiments, the oil is present in the emulsion of the application in an amount of about 8 wt%, about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt% or about 30 wt% and values therebetween. In some embodiments, the oil is present in the emulsion of the application in an amount of about 20 wt%.
[0096] In some embodiments, the weight ratio of oil to one or more cannabinoid compounds is about 100:1 to about 1 :1. In some embodiments, the weight ratio of oil to at least one cannabinoid or cannabis derived compound is about 80:1 , about 20:1 , about 7:1 , about 2:1 , or about 1 :1.
[0097] In some embodiments, the emulsion further comprises one or more pH adjusting agents selected from sodium acetate, phosphoric acid, acetic acid, lactic acid, fumaric acid, adipic acid, malic acid, tartaric acid, citric acid, hydrochloric acid, sulfuric acid, potassium hydroxide, salts thereof, and combinations thereof. In some embodiments, the one or more pH adjusting agents comprise citric acid and potassium hydroxide. In some embodiments, the citric acid is anhydrous citric acid.
[0098] In some embodiments, the one or more pH adjusting agents are present in the emulsion of the application in an amount of about 0.1 wt% to about 5 wt% of theemulsion. In some embodiments, the one or more pH adjusting agents are present in the emulsion of the application in an amount of about 0.5 wt%, about 1 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, or about 4.5 wt% and values therebetween. In some embodiments, the one or more pH adjusting agents are present in the emulsion of the application in an amount of about 0.9 wt%.
[0099] In some embodiments, the pH of the final emulsion is below about 4. In some embodiments, the pH of the final emulsion is from about 2 to about 3.2.
[0100] In some embodiments, the emulsion further comprises one or more antifoaming agents. The anti-foaming agents which can be used in the emulsion of the application are any anti-foaming agents known in the art. Examples include, but are not limited to polydimethylsiloxane, fatty acid ester, silicon dioxide, vegetable oil based anti-foaming agents and the like.
[0101] In some embodiments, the one or more anti-foaming agents are present in the emulsion of the application in an amount of about 0.005 wt% to about 0.1 wt % of the emulsion. In some embodiments, the one or more anti-foaming agents are present in the emulsion of the application in an amount of about 0.01 wt%, about 0.05 wt%, or about 0.08 wt% and values therebetween. In some embodiments, the one or more anti-foaming agents are present in the emulsion in an amount of about 0.01 wt%.
[0102] In some embodiments, the encapsulation of the one or more cannabinoid compounds by the complex is achieved by homogenization of the mixture of the protein complex and the one or more cannabinoid compounds. This results in the formation of microparticles of the one or more cannabinoid compounds, which are encapsulated in the protein complex.
[0103] In some embodiments, the emulsion of the application has an average particle size of below about 1000 nm. In some embodiments, the emulsion of the application has an average particle size of about 50 nm to about 900 nm, about 50 nm to about 800 nm, about 50 nm to about 700 nm, about 50 nm to about 600 nm, about 50 nm to about 500 nm, about 50 to about 400 nm, about 50 nm to about 300 nm, or about 900 nm, about 800 nm, about 700 nm, about 600 nm, about 500 nm, or about 400 nm and values therebetween. In some embodiments, the particle size is determined using dynamic light scattering method.
[0104] While not wishing to be limited by theory, the protein complex, which is adsorbed at the oil-water interface, greatly improves the stability of the emulsion of the application and protects the one or more cannabinoid compounds of the application from exposure to oxidants and pro-oxidants. Pro-oxidants, such as metal ions, are able to lower the activation energy for the initiation of oxidation. Some of these metal ions are bound by the protein complexes, which reduces their negative impact on the oxidation of the one or more cannabinoid compounds.
[0105] In some embodiments, the emulsion of the application is a stable oil-in- water emulsion. In some embodiments, the emulsion of the application is stable at room temperature for at least two weeks orfor at least three weeks. Thus, the emulsion of the applications remains free from degradation of the one or more cannabinoid compounds of the application and maintains homogeneous content and appearance. Determination whether an emulsion has lost its stability may be carried out by any of the following techniques: measurement of particle size, zeta potential, light scattering, focused beam reflectance measurement, centrifugation, rheology, potency analysis of the cannabinoids and other active ingredients, assessment of visual appearance or a combination thereof.
[0106] In some embodiments, the emulsion of the application has zeta potential of above about 30 mV. In some embodiments the emulsion of the application has zeta potential of above about 33 mV, above about 35 mV, above about 40, or above about 45 mV. In some embodiments, the emulsion of the application has zeta potential of between about 40 mV to about 50 mV.
[0107] In some embodiments, the present application includes an emulsion comprising: a) about 0.25 wt% to about 13 wt% of one or more cannabinoid compounds; b) about 0.25 wt% to about 5 wt% of casein protein; c) about 0.25 wt% to about 5 wt% of whey protein; d) about 8 wt% to about 30 wt% oil; e) optionally about 0.1 wt% to about 5 wt% of one or more pH adjusting agents; f) optionally about 0.005 wt% to about 0.1 wt % of one or more anti-foaming agents; andg) water to make 100%.
[0108] In some embodiments, the present application includes an emulsion comprising: a) about 1 wt% to about 12 wt% of one or more cannabinoid compounds; b) about 0.8 wt% to about 2 wt% of casein protein; c) about 0.8 wt% to about 2 wt% of whey protein; d) about 8 wt% to about 22 wt% oil; e) optionally about 2 wt% to about 5 wt% of one or more pH adjusting agents; f) optionally about 0.005 wt% to about 0.1 wt % of one or more anti-foaming agents; and g) water to make 100%.
[0109] In some embodiments, the present application includes an emulsion comprising: a) about 1 wt% to about 12 wt% of one or more cannabinoid compounds; b) about 1 .3 wt% of casein protein; c) about 1 .3 wt% of whey protein; d) about 8 wt% to about 22 wt% oil; e) optionally about 2 wt% to about 5 wt% of one or more pH adjusting agents; f) optionally about 0.005 wt% to about 0.1 wt % of one or more anti-foaming agents; and g) water to make 100%.
[0110] In some embodiments, the emulsion of the application has the advantage that it is resistant to oxidation, has a long shelf-life and / or is stable at high temperature processing, thus allowing it to be heat-treated or sterilized. This is of great benefit as it allows one or more encapsulated cannabinoid compounds of the application to be added to products that must be sterilized before consumption. Further, the application provides convenient formulations of cannabinoid compounds useful for enhancing or creating aqueous soluble cannabinoid compositions. The emulsion of the application may be useful, for example, to prepare compositionsselected from a beverage, gel, gelatin and concentrate and as a beverage enhancer. As such, the emulsion of the application is for use in compositions selected from beverages, gels, gelatins and concentrates and as a beverage enhancer.
[0111] The present application also includes a composition selected from a beverage, gel, gelatin, concentrate and beverage enhancer, wherein the composition comprises the emulsion of the present application.
[0112] In some embodiments, the composition is a beverage. In some embodiments, the beverage is selected from water, milk, tea, coffee, fruit juice (e.g., orange, apple, cranberry, pear, currant, etc.), vegetable juice (e.g., carrot, tomato, etc.), nutritional supplement, natural health product, punch and carbonated drink (e.g. sparkling water, soda water, sports drink, and soft drink, such as a cola). In some embodiments, the beverage is the nutritional supplement or the natural health product.
[0113] In some embodiments, the one or more cannabinoids are present in the composition of the application at a concentration of about 0.001 mg / ml to about 5 mg / mL, about 0.01 mg / mL to about 4 mg / mL, about 0.1 mg / mL to about 3 mg / mL, about 0.5 mg / mL to about 2 mg / mL, about 1 mg / mL to about 1 .5 mg / mL, and values therebetween. In some embodiments, the one or more cannabinoids are present in the composition of the application at a concentration of about 0.2 mg / mL, about 0.4 mg / mL, about 0.85 mg / mL, or about 1.7 mg / mL.
[0114] In some embodiments, the one or more cannabinoids are present in the composition of the application in an amount of about 10 mg to about 500 mg, about 15 mg to about 450 mg, about 20 mg to about 400 mg, about 50 mg to about 300 mg, about 100 mg to about 200 mg, and values therebetween. In some embodiments, the one or more cannabinoids are present in a composition of the application in an amount of about 20 mg, about 50 mg, about 100 mg, about 210 mg, or about 420 mg.
[0115] In some embodiments, the composition of the application comprises a liquid selected from water, oil, and alcohol. In some embodiments, the liquid is selected from plain water, alcohol, non-alcoholic drink, soft drink, fruit juice, vegetable juice, tea, coffee, milk, punch or other hot, room temperature or cold liquids used in drinks. The composition of the application can be caffeinated or non-caffeinated. Such compositions may be produced in ready to use form or be produced in a form suitable for preparation in final consumable form at or proximate to the time of ingestion.
[0116] In some embodiments, the liquid is present in the composition of the application in an amount of between about 50% wt% to about 99.99% wt% of the composition of the application. In some embodiments, the liquid is present in the composition of the application in an amount of between about 80% wt% to about 99.99% wt%. In some embodiments, the liquid is present in the composition of the application in an amount of between about 80% wt% to about 99.9% wt%. In some embodiments, the liquid is present in the composition of the application in an amount of between about 95% wt% to about 99.9% wt%. In some embodiments, the liquid is water.
[0117] In some embodiments, the composition of the application comprises between about 0.5% wt% to about 25% wt% of the emulsion of the application, between about 1 % wt% to about 10% wt% of the emulsion of the application, or between about 1 % wt% to about 5% wt% of the emulsion of the application, based on the total weight of the composition. In some embodiments, the composition of the application comprises between about 0.5% wt% to about 3% wt% of the emulsion of the application based on the total weight of the composition.
[0118] In some embodiments, the emulsions and the compositions of the application include any number of other additives, including without limitation a solvent, a bulking agent, an antioxidant such as naturally derived antioxidant (e.g. polyphenols and anthrocyanidins), or a nutritional supplement. These additives may be used either alone or in combination to improve, for example, the chemical and / or physical properties, stability, nutritional profile, taste, colour and / or viscosity, of the emulsions and the compositions of the application.
[0119] In some embodiments, the emulsions and the compositions of the application further include one or more suitable types of modifiers and additives, the one or more of additives are selected from anti-foaming agents, stabilizers, viscosity modifiers, emulsifiers, oils, thickening agents, minerals, acids, bases, vitamins, flavours, colourants, sweeteners (e.g. liquid sweeteners), and the like and combinations thereof, to provide improved solubility, stability, bioavailability, colour and taste. In some embodiments, the compositions of the application comprise a stabilizer to maintain stability and prevent degeneration. Examples of stabilizers include but are not limited to acai gum (gum Arabic), agar-agar, ammonium alginate, calcium alginate, carob bean gum (locust bean gum), chondrus extract (carrageenan),ghatti gum, guar gum, pectin, potassium alginate, sodium alginate, sterculia gum (karaya gum), tragacanth, gelatin, lecithin, mono-glycerides, di-glycerides, maltodextrin, xanthan gum, proplylene glycol alginates (PGA), microcrystalline cellulose, sodium carboxymethyl cellulose, Purity Gum 2000 (modified starch), pectin, carrageenan, casein and inulin. In some embodiments, the stabilizer is pectin. In some embodiments, the pectin is present in the composition in an amount of between about 0.1 % wt% to about 5% wt% of the composition of the application.
[0120] In some embodiments, the emulsions and the compositions of the application further comprise at least one nutritional supplement. In some embodiments, the nutritional supplements are selected from vitamin A, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K calcium, phosphorus, potassium, sulfur, sodium, chlorine, magnesium, iron, cobalt, copper, zinc, molybdenum, iodine, selenium, manganese, nickel, chromium, fluorine, boron, strontium histidine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, threonine, tryptophan, valine, alpha-linoleic acid, linoleic acid, L-theanine, malic acid, curcumin, or a combination thereof.
[0121] In some embodiments compositions are packaged as individual packages, suitably single use packages, or as multiple packages. In some embodiments, the packaging is in air tight containers. In some embodiments, packaging is comprised of paper, plastic, metal, and / or glass. In some embodiments, compositions include bubble containing or producing liquids with dissolved gas or liquids capable of producing gas proximately in time of consumption. In some embodiments, compositions with dissolved gas are created by a method comprising addition of carbon dioxide, ozone, oxygen, or nitrogen. In some embodiments, for compositions with dissolved gas, dissolved gas is added to the composition by methods comprising application of pressure, or adding water with the dissolved gas. The dissolved gas is released from the composition when pressure is reduced as effervescence.
[0122] In some embodiments, the emulsion of the application is further dried to form a powder formulation for use in the composition of the application. In some embodiments, the emulsion of the application is dried using any method known in the art to evaporate the water phase of the emulsion, and possibly none, some oressentially all of the oil. In some embodiments, the emulsion of the application is spray dried to form the powder formulation. Alternative methods include, but are not limited to, pan coating, air-suspension coating, centrifugal extrusion, vibrational nozzle technique, freeze-drying or using a food dehydrator. As such, the emulsion of the application is for use in a powder formulation.
[0123] The present application also includes a powder formulation which comprises the emulsion of the present application.
[0124] In some embodiments, the resulting powder formulation is diluted with a bulking agent or a mixture of bulking agents. Suitable bulking agents include, for example, gum arabic, waxy maize starch, dextrin, maltodextrin, polydextrose, inulin, fructooligosaccharide, sucrose, glucose, fructose, galactose, lactose, maltose, trehalose, cellobiose, lactulose, ribose, arabinose, xylose, lyxose, allose, altrose, mannose, gulose, talose, erythritol, threitol, arabitol, xylitol, mannitol, ribitol, galactitol, fucitol, inositol, maltitol, sorbitol, isomalt, lactitol, polyglycitol, iditol, volemitol, maltotriitol, maltotetraitol, maltol, stevia, stevio side, rebaudio side, neotame, sucralose, saccharin, sodium cyclamate, aspartame, acesulfame potassium, chitin, and chitosan, and combinations thereof.
[0125] In some embodiments, the bulking agent furthers comprises a sweetener, pH modifier, pH stabilizer, antimicrobial preservative, antioxidant, texture modifier, or colourant, or combinations thereof.
[0126] In some embodiments, once prepared, the powder formulation is mixed directly in a liquid composition of the application or is dissolved in a solution to then be added to the composition of the application. In some embodiments, the powder formulation is prepared and packaged using any packaging known in the art. For example, in some embodiments, the powder formulation is packaged as a single serving or multiple servings in a metal, glass, and / or plastic container. In some embodiments, the powder formulation is packaged as a single serving stick pack or pouch.
[0127] In some embodiments, the emulsions of the application enhance or maintain the stability of the one or more cannabinoids in the emulsion and in the composition produced therefrom. In some embodiments, the composition of the application is stable at room temperature for at least one week with <30% decrease,<20% decrease or less than 10% decrease in amount of the one or more cannabinoids. In some embodiments, the composition of the application is stable at room temperature for at least two weeks with <40% decrease, <30% decrease or less than 25% decrease in amount of the one or more cannabinoids. Thus, the emulsion of the application remains free from degradation of one or more cannabinoids and maintains homogeneous appearance.III. Method of Preparing the Emulsions of the Application
[0128] The present application includes a method of preparing an emulsion comprising one or more cannabinoid compounds, the method comprising: a) heating an aqueous solution of casein protein and whey protein to form an aqueous solution comprising a casein protein and whey protein complex; b) mixing the one or more cannabinoid compounds with an oil to form a first mixture; c) dispersing the mixture formed in b) in the aqueous solution of a) to form a second mixture; and d) homogenizing the second mixture formed in c) to form the emulsion.
[0129] In some embodiments, the complex comprises whey protein and casein protein which are cross-linked or covalently bonded.
[0130] In some embodiments, the pH of the aqueous solution of casein protein and whey protein complex is adjusted to about 6 to about 9, prior to the heating in a). In some embodiments, the pH of the aqueous solution of casein protein and whey protein is adjusted to about 6.5 to about 8, prior to the heating in a). In some embodiments, the pH of the aqueous solution of casein protein and whey protein is adjusted to about 7.5 to about 8, prior to the heating in a). In some embodiments, the pH of the aqueous solution is adjusted using any pH adjusting agent, such as potassium hydroxide, sodium hydroxide, disodium hydrogen phosphate, sodium bicarbonate, sodium phosphate tribasic, dipotassium hydrogen phosphate, and combinations thereof.
[0131] In some embodiments, the casein protein and whey protein complex is formed by heating the aqueous solution of casein and whey protein at about 70° C to about 100° C. In some embodiments, the complex is formed by heating the aqueoussolution of casein and whey protein at about 80° C to about 95° C, or at about 90° C. In some embodiments, the aqueous solution of casein and whey protein is heated for about 1 minute to about 30 minutes, from about 5 minutes to about 20 minutes, or for about 5 minutes. In some embodiments, after heating, the aqueous solution is cooled to below about 20° C, or to about 10° C.
[0132] While not wishing to be limited by theory, it is believed that heating the casein and whey proteins causes unfolding of whey proteins which releases the sulfhydryl groups of the respective proteins, allowing them to form intermolecular disulfide bond linkages with caseins. Excess sulfhydryl groups present in the whey proteins remain in their reduced state. These free sulfhydryl group confer additional antioxidant activity on the complex.
[0133] In some embodiments, after heating in a), the pH of the aqueous solution of casein protein and whey protein complex is adjusted to below about 4. In some embodiments, the pH of the aqueous solution of casein protein and whey protein complex is adjusted to about 2 to about 3.2 after the heating in a). In some embodiments, the pH of the aqueous solution of casein protein and whey protein complex is adjusted using any pH adjusting agent, such as sodium acetate, phosphoric acid, acetic acid, lactic acid, fumaric acid, adipic acid, malic acid, tartaric acid, citric acid, hydrochloric acid, sulfuric acid, salts thereof, and combinations thereof.
[0134] In some embodiments, the mixing of the one or more cannabinoid compounds with an oil in b) further comprises sonication. In some embodiments, the sonication is performed in an ultrasonic bath at about 80 kHz at 100 % power for about 10 minutes. In some embodiments, the sonication is performed under conditions to render the mixture homogenous.
[0135] In some embodiments, the mixing of the one or more cannabinoid compounds with an oil in c) further comprises heating. In some embodiments, the mixing in c) is performed at a temperature of about 40° C to about 50° C.
[0136] In some embodiments, the homogenizing in d) is performed using any known method. Suitable methods include, for example, high-pressure homogenization (HPH), high-shear homogenization or microfluidization. In some embodiments, the homogenizing in d) is performed by a top homogenizer. In some embodiments, thehomogenizing in d) comprises using a microfluidizer at about 2,500 psi and about 40,000 psi pressure. In some embodiments, the microfluidizer is set at about 10,000 psi and about 40,000 psi, or at about 20,000 psi and about 40,000 psi of pressure is applied to create an emulsion system with particles less than about 500 nm.
[0137] In some embodiments, the complex comprises whey protein and casein protein which are cross-linked or covalently bonded. In some embodiments, in the emulsion, the one or more cannabinoid compounds is encapsulated in the complex of whey protein and casein protein.
[0138] In some embodiments, the one or more cannabinoid compounds are selected from cannabigerolic acid (CBGA), cannabigerolic acid monomethylether (CBGAM), cannabigerol (CBG), cannabigerol monomethylether (CBGM), cannabigerovarinic acid (CBGVA), cannabigerovarin (CBGV), cannabichromenic Acid (CBCA), cannabichromene (CBC), cannabichromevarinic acid (CBCVA), cannabichromevarin (CBCV), cannabidiolic acid (CBDA), cannabidiol (CBD), A6 cannabidiol (A6-CBD), cannabidiol monomethylether (CBDM), cannabidiol-C4 (CBD C4), cannabidivarinic acid (CBDVA), cannabidivarin (CBDV), cannabidiorcol (CBD C1), tetrahydrocannabinolic acid A (THCA-A), tetrahydrocannabinolic acid B (THCA- B), tetrahydrocannabinol (THC or A9-THC), A8-tetrahydrocannabinol (A8-THC), A10- tetrahydrocannabinol (A10-THC), tetrahydrocannabinolic acid C4 (THCA-C4), tetrahydrocannbinol C4 (THC C4), tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabivarin (THCV), A8-tetrahydrocannabivarin (A8-THCV), A9 tetrahydrocannabivarin (A9-THCV), tetrahydrocannabiorcolic acid (THCA-C1), tetrahydrocannabiorcol (THC-C1), delta 7 cis iso tetrahydrocannabivarin, A8 tetrahydrocannabinolic acid (A8-THCA), A9 tetrahydrocannabinolic acid (A9-THCA), cannabicyclolic acid (CBLA), cannabicyclol (CBL), cannabicyclovarin (CBLV), cannabielsoic acid A (CBEA-A), cannabielsoic acid B (CBEA-B), cannabielsoin (CBE), cannabinolic acid (CBNA), cannabinol (CBN), cannabinol methylether (CBNM), cannabinol-C4 (CBN-C4), cannabivarin (CBV), cannabino-C2 (CBN-C2), cannabiorcol (CBN-C1), cannabinodiol (CBND), cannabinodivarin (CBDV), cannabitriol (CBT), 11 hydroxy-A9-tetrahydrocannabinol (11 OH-THC), 11 nor 9-carboxy-A9- tetrahydrocannabinol ethoxy-cannabitriolvarin (CBTVE), 10 ethoxy-9-hydroxy-A6a- tetrahydrocannabinol, cannabitriolvarin (CBTV), 8,9 dihydroxy-A6a(10a)- tetrahydrocannabinol (8,9-Di-OH-CBT-C5), dehydrocannabifuran (DCBF),cannbifuran (CBF), cannabichromanon (CBCN), cannabicitran (CBT), 10 oxo- A6a(10a)-tetrahydrocannabinol (OTHC), A9-cis-tetrahydrocannabinol (cis-THC), cannabiripsol (CBR), 3,4,5,6-tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n- propyl-2,6-methano-2H-1-benzoxocin-5-methanol (OH-iso-HHCV), and trihydroxy- delta-9-tetrahydrocannabinol (triOH-THC), or any combination thereof.
[0139] In some embodiments, the one or more cannabinoid compounds are a salt, isomer, enantiomer, or optically active derivative thereof. In some embodiments, the one or more cannabinoid compounds are derived from a natural source. In some embodiments, the one or more cannabinoid compounds are derived from a plant of the Cannabis genus, e.g., Cannabis sativa, Cannabis indica, Cannabis hybrid, or other genera. In some embodiments, the one or more cannabinoid compounds are synthetic or semi-synthetic cannabinoids.
[0140] In some embodiments, the one or more cannabinoid compounds are comprised in a distillate, an isolate, cannabis oil, cannabis extract or a combination thereof. In some embodiments, the one or more cannabinoid compounds are comprised in a distillate. In some embodiments, the one or more cannabinoid compounds are comprised in an isolate. In some embodiments, the one or more cannabinoid compounds are comprised in a cannabis oil. In some embodiments, the one or more cannabinoid compounds are comprised in a cannabis extract.
[0141] In some embodiments, the distillate is obtained from cannabis extract or cannabis oil. In some embodiments, the cannabis extract or cannabis oil are distilled to obtain the distillate. In some embodiments, the distillate comprises from about 70 wt% to about 95 wt %, from about 75 wt% to about 90 wt %, from about 80 wt% to about 95 wt %, from about 85 wt% to about 95 wt % of one or more cannabinoid compounds. In some embodiments, the distillate comprises about 85, 86, 87, 88, 89, 90, 91 , 92 or 93 wt % of one or more cannabinoid compounds, and values therebetween.
[0142] In some embodiments, the isolate comprises from about 95 wt% to about 100 wt%, about 97 wt% to about 100 wt%, or about 98 wt% to about 100 wt % of one or more cannabinoid compounds, and values therebetween.
[0143] In some embodiments, the cannabis oil containing one or more cannabinoid compounds is extracted from a plant of the Cannabis genus, e.g.,Cannabis sativa, Cannabis indica, Cannabis hybrid, or other genera, using various techniques known in the art, such as solvent-based extraction.
[0144] In some embodiments, the cannabis extract containing one or more cannabinoid compounds is extracted from a plant of the Cannabis genus, e.g., Cannabis sativa, Cannabis indica, Cannabis hybrid, or other genera, using any suitable technique for separating cannabinoids from the plant. In some embodiments, the extract can be obtained using solvent-based extraction.
[0145] In some embodiments, the one or more cannabinoid compounds is or comprises CBG, or a salt, isomer, enantiomer, or optically active derivative thereof. In some embodiments, the one or more cannabinoid compounds is or is comprised in a CBG distillate. In some embodiments, the one or more cannabinoid compounds is or is comprised in a CBG isolate.
[0146] In some embodiments, the one or more cannabinoid compounds is or comprises CBD, or a salt, isomer, enantiomer, or optically active derivative thereof. In some embodiments, the one or more cannabinoid compounds is or is comprised in a CBD distillate. In some embodiments, the one or more cannabinoid compounds is or is comprised in a CBD isolate.
[0147] In some embodiments, the one or more cannabinoid compounds is or comprises THC, or a salt, isomer, enantiomer, or optically active derivative thereof. In some embodiments, the one or more cannabinoid compounds is or is comprised in a THC distillate. In some embodiments, the one or more cannabinoid compounds is or is comprised in a THC isolate.
[0148] In some embodiments, the emulsion of the application comprises one cannabinoid (single cannabinoid). In some embodiments, the emulsion of the application comprises two or more cannabinoid compounds. In some embodiments, the emulsion of the application comprises two, three, four or more cannabinoid compounds. In some embodiments, the emulsion of the application comprises two cannabinoid compounds. In some embodiments, the emulsion of the application comprises two or more cannabinoid compounds comprised in a distillate, an isolate, cannabis oil, cannabis extract or a combination thereof.
[0149] In some embodiments, the one or more cannabinoid compounds are present in the emulsion in an amount of about 0.25 wt% to about 13 wt% of theemulsion. In some embodiments, the one or more cannabinoid compounds are present in the emulsion in an amount of about 0.25 wt%, about 0.5 wt%, about 1 wt%, about 1 .5 wt%, about 2 wt%, about 4 wt%, about 5 wt%, about 7 wt%, about 8.5 wt% or about 10 wt% and values therebetween. In some embodiments, the one or more cannabinoid compounds are present in the emulsion in an amount of about 0.5 wt%. In some embodiments, the one or more cannabinoid compounds are present in the emulsion in an amount of about 1.2 wt%. In some embodiments, the one or more cannabinoid compounds are present in the emulsion at in an amount of about 2.4 wt%. In some embodiments, the one or more cannabinoid compounds are present in the emulsion in an amount of about 5.1 wt%. In some embodiments, the one or more cannabinoid compounds are present in the emulsion in an amount of about 10.2 wt%.
[0150] In some embodiments, the emulsion further comprises one or more terpenes, one or more terpenoids, one or more flavonoids, and any combinations thereof. In some embodiments, the emulsion further comprises one or more terpenes and / or one or more terpenoids. In some embodiments, the one or more terpenes and / or one or more terpenoids are selected from abietane, alpha- bisabolol, alphaphellandrene, alpha-pinene, beta-caryophyllene, beta-myrcene, beta-pinene, borneol, cadinene, camphene, camphor, carvacrol, caryophyllene acetate, caryophyllene oxide, cedrane, cembrene, citral, citronellol, copaene, dextro carvone, dextro fenchone, eucalyptol, eugenol, farnesene, gama-3-carene, gamma-terpinene, geraniol, geranyl acetate, guaiazulene, guaiene, humulene, isopulegol, labdane, limonene, linalool, longifolene, menthol, nerol, nerolidol, ocimene, ocimene, patchoulol, p-cymene, phytane, phytol, pinene, pulegone, retinal, retinol, sclarene, stemarene, stemoden, terpineol, terpinolele, terpinolene, texadiene, thymol, valencene, valencene, vetivazulene, and zingiberene, or any combination thereof, or a salt, isomer, enantiomer, or optically active derivative thereof. In some embodiments, the one or more terpenes and / or one or more terpenoids comprise hemiterpenes, monoterpenols, terpene esters, diterpenes, monoterpenes, polyterpenes, tetraterpenes, terpenoid oxides, sesterterpenes, sesquiterpenes, norisoprenoids, or their derivatives, as well as isomeric, enantiomeric, or optically active derivatives thereof. In some embodiments, the derivatives of the one or more terpenes and / or one or more terpenoids comprise terpenoids, hemiterpenoids, monoterpenoids, sesquiterpenoids, sesterterpenoid, sesquarterpenoids, tetraterpenoids, triterpenoids,tetraterpenoids, polyterpenoids, isoprenoids, or steroids. In some embodiments, the one or more terpenes and / or one or more terpenoids comprise a-(alpha), p-(beta), y- (gamma), oxo-, isomers, or any combinations thereof.
[0151] In some embodiments, the emulsion further comprises one or more flavonoids selected from bioflavonoids, isoflavonoids and neoflavonoids. In some embodiments, the one or more flavonoids are present in the emulsion in an amount of from about 0.00001 wt% to about 0.01 wt%.
[0152] In some embodiments, the one or more terpenes and / or one or more terpenoids are present in the emulsion in an amount of about 0 wt% to about 13 wt% of the emulsion. In some embodiments, the one or more terpenes and / or one or more terpenoids are present in the emulsion in an amount of about 0 to about 0.1 wt%, about 0 to about 0.5 wt%, about 0.5 to about 1 wt%, about 0 to about 1 wt%, about 0 to about 5 wt%, about 0 to about 12 wt%, about 1 to about 2 wt%, about 2 to about 3 wt%, about 3 to about 4 wt%, about 4 to about 5 wt%, about 5 to about 7.5 wt%, about 5 to about 10 wt% or about 10 to about 12.5 wt%, and values therebetween.
[0153] In some embodiments, the whey protein used in the emulsion of the application is any milk serum protein or protein composition known in the art, including, but not limited to, protein isolate, whey protein concentrate, a-lactalbumin and / or p- lacoglobulin. In some embodiments, the whey protein is selected from whey protein isolate, whey protein concentrate, a-lactalbumin and p-lacoglobulin. In some embodiments, the whey protein is whey protein isolate.
[0154] In some embodiments, the casein protein used in the emulsion of the application is any casein protein known in the art. In some embodiments, the casein protein is selected from a-casein, K-casein, p-casein, b-casein, and their salts, such as sodium, potassium, calcium and ammonium, or mixtures thereof. In some embodiments, the casein protein is sodium caseinate.
[0155] In some embodiments, the whey protein is present in the emulsion in an amount of about 0.25 wt% to about 5 wt% of the emulsion. In some embodiments, the whey protein is present in the emulsion in an amount of about 0.5 wt%, about 1 wt%, about 1 .25 wt%, about 1 .5 wt%, about 1 .8 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt% or about 5 wt% and values therebetween. In some embodiments, the whey protein is present in the emulsion inan amount of about 0.5 wt%. In some embodiments, the whey protein is present in the emulsion in an amount of about 1 .3 wt%. In some embodiments, the casein protein is present in the emulsion in an amount of about 3 wt%.
[0156] In some embodiments, the casein protein is present in the emulsion in an amount of about 0.25 wt% to about 5 wt% of the emulsion. In some embodiments, the casein protein is present in the emulsion in an amount of about 0.5 wt%, about 1 wt%, about 1.25 wt%, about 1.5 wt%, about 1.8 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt% or about 5 wt% and values therebetween. In some embodiments, the casein protein is present in the emulsion in an amount of about 0.5 wt%. In some embodiments, the casein protein is present in the emulsion in an amount of about 1 .3 wt%. In some embodiments, the casein protein is present in the emulsion in an amount of about 3 wt%.
[0157] In some embodiments, the weight ratio of casein protein to whey protein is about 10:1 to about 1 :10. In some embodiments, the weight ratio of casein protein to whey protein is about 6:1 to about 1 :6, about 3:1 to about 1 :3, about 2:1 to about 1 :2 or about 1 :1. In some embodiments, the weight ratio of casein protein to whey protein is about 6:1 to about 1 :6. In some embodiments, the weight ratio of casein protein to whey protein is 1 :1 .
[0158] In some embodiments, the whey protein is present in the emulsion in an amount of about 1.3 wt% and the casein protein is present in the emulsion in an amount of about 1 .3 wt%.
[0159] In some embodiments, the water is present in the emulsion of the application in an amount of about 65 wt% to about 80 wt% of the emulsion. In some embodiments, the water is present in the emulsion of the application in an amount of about 68 wt%, about 70 wt%, about 73 wt%, about 75 wt%, or about 78 wt% and values therebetween.
[0160] In some embodiments, the oil which is used in the emulsion of the application includes any oil used in food, pharmaceutical or cosmetic industries. In some embodiments, the oil is an edible oil. In some embodiments, the oil is extracted from any appropriate source such as a marine animal, plant, phytoplankton or algae including microalgae, or may be produced synthetically. The oil can be used in nonpurified, purified or highly purified form, concentrated or non-concentrated. The oil aidsin the dissolution of the cannabinoid or cannabis derived compound and allows for emulsification of the cannabinoid and cannabis-derived compounds.
[0161] In some embodiments, the oil is an omega-3 oil. In some embodiments, the oil contains omega-3 fatty acids or omega-3 fatty acid precursors such as a- linolenic acid. In some embodiments, the fatty acids that are present in the omega-3 oil are selected from one or more of all-cis-7,10,13-hexadecatrienoic acid; a-linolenic acid (ALA) (all-cis-9,12,15-octadecatrienoic acid); stearidonic acid (SDA) (all-cis- 6,9,12,15-octadecatetraenoic acid); eicosatrienoic acid (ETE) (all-cis- 11 ,14,17- eicosatrienoic acid); eicosatetraenoic acid (ETA) (all-cis-8,11 ,14,17-eicosatetraenoic acid); eicosapentaenoic acid (EPA) (all-cis-5,8,11 ,14,17-eicosapentaenoic acid); docosapentaenoic acid (DPA) (all-cis-7,10,13,16,19-docosapentaenoic acid); docosahexaenoic acid (DHA) (all-cis-4,7,10,13,16,19-docosahexaenoic acid); tetracosapentaenoic acid (all-cis-9,12,15,18,21-tetracosapentaenoic acid); and tetracosahexaenoic acid (nisinic acid) (all-cis-6,9, 12, 15,18,21 -tetracosahexaenoic acid). In some embodiments, the omega-3 fatty acids provide anti-inflammatory properties.
[0162] In some embodiments, the omega-3 is selected from oils obtained from fish such as salmon, tuna, herring, mackerel, anchovies, sardines, pollock, cod, catfish, flounder, grouper, halibut, mahi mahi, orange roughy, red snapper, shark, swordfish, tilefish, plankton, algae, krill and / or green-lipped mussel, and / or plant oils such as canola oil, borage oil, evening primrose oil, safflower oil, sunflower oil, flaxseed oil, wheat germ oil, algal oil, and / or grapeseed oil and oils obtained from chia seeds, kiwifruit seeds, perilla seeds, lingonberry seeds, camelina seeds, purslane seeds, black raspberry seeds, hemp seeds, butternut, walnuts, pecan nuts, and / or hazel nuts. In some embodiments, the oil is sunflower oil. In some embodiments, the oil is algal oil.
[0163] In some embodiments, the oil is present in the emulsion of the application in an amount of about 8 wt% to about 30 wt% of the emulsion. In some embodiments, the oil is present in the emulsion of the application in an amount of about 8 wt%, about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt% or about 30 wt% and values therebetween. In some embodiments, the oil is present in the emulsion of the application in an amount of about 20 wt%.
[0164] In some embodiments, the weight ratio of oil to one or more cannabinoid compounds is about 100:1 to about 1 :1. In some embodiments, the weight ratio of oil to at least one cannabinoid or cannabis derived compound is about 80:1 , about 20:1 , about 7:1 , about 2:1 , or about 1 :1.
[0165] In some embodiments, the emulsion further comprises one or more pH adjusting agents selected from sodium acetate, phosphoric acid, acetic acid, lactic acid, fumaric acid, adipic acid, malic acid, tartaric acid, citric acid, hydrochloric acid, sulfuric acid, potassium hydroxide, salts thereof, and combinations thereof. In some embodiments, the one or more pH adjusting agents comprise citric acid and potassium hydroxide. In some embodiments, the citric acid is anhydrous citric acid.
[0166] In some embodiments, the one or more pH adjusting agents are present in the emulsion of the application in an amount of about 0.1 wt% to about 5 wt% of the emulsion. In some embodiments, the one or more pH adjusting agents are present in the emulsion of the application in an amount of about 0.5 wt%, about 1 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, or about 4.5 wt% and values therebetween. In some embodiments, the one or more pH adjusting agents are present in the emulsion of the application in an amount of about 0.9 wt%.
[0167] In some embodiments, the emulsion further comprises one or more antifoaming agents. The anti-foaming agents which can be used in the method of the application are any anti-foaming agents known in the art. Examples include, but are not limited to polydimethylsiloxane, fatty acid ester, silicon dioxide, vegetable oil based anti-foaming agents and the like.
[0168] In some embodiments, the one or more anti-foaming agents are present in the emulsion of the application in an amount of about 0.005 wt% to about 0.1 wt % of the emulsion. In some embodiments, the one or more anti-foaming agents are present in the emulsion of the application in an amount of about 0.01 wt%, about 0.05 wt%, or about 0.08 wt% and values therebetween. In some embodiments, the one or more anti-foaming agents are present in the emulsion in an amount of about 0.01 wt%.
[0169] In some embodiments, the emulsion of the application has an average particle size of below about 1000 nm. In some embodiments, the emulsion of the application has an average particle size of about 50 nm to about 900 nm, about 50 nm to about 800 nm, about 50 nm to about 700 nm, about 50 nm to about 600 nm, about50 nm to about 500 nm, about 50 to about 400 nm, about 50 nm to about 300 nm, or about 900 nm, about 800 nm, about 700 nm, about 600 nm, about 500 nm, or about 400 nm and values therebetween. In some embodiments, the particle size is determined using dynamic light scattering method.
[0170] While not wishing to be limited by theory, the protein complex, which is adsorbed at the oil-water interface, greatly improves the stability of the emulsion of the application and protects the one or more cannabinoid compounds of the application from exposure to oxidants and pro-oxidants. Pro-oxidants, such as metal ions, are able to lower the activation energy for the initiation of oxidation. Some of these metal ions are bound by the protein complexes, which reduces their negative impact on the oxidation of the one or more cannabinoid compounds.
[0171] In some embodiments, the emulsion of the application is a stable oil-in- water emulsion. In some embodiments, the emulsion of the application is stable at room temperature for at least two weeks or for at least three weeks. Thus, the emulsion of the applications remains free from degradation of the one or more cannabinoid compounds of the application and maintains homogeneous content and appearance. Determination whether an emulsion has lost its stability may be carried out by any of the following techniques: measurement of particle size, zeta potential, light scattering, focused beam reflectance measurement, centrifugation, rheology, potency analysis of the cannabinoids and other active ingredients, assessment of visual appearance or a combination thereof.
[0172] In some embodiments, the emulsion of the application has zeta potential of above about 30 mV. In some embodiments the emulsion of the application has zeta potential of above about 33 mV, above about 35 mV, above about 40, or above about 45 mV. In some embodiments, the emulsion of the application has zeta potential of between about 40 mV to about 50 mV.
[0173] The present application also includes an emulsion of the application prepared by the method of the application.
[0174] In some embodiments, the method of the application further comprises heat treating or sterilizing the emulsion of the present application. In some embodiments, the emulsion is sterilized by ultra-high temperature (UHT) (e.g. 140° C. for 5 seconds). In some embodiments, the emulsion is pasteurized (e.g. 70° C. for 30minutes). In some embodiments, the emulsion is retorted (e.g. heated in a sealed container at 120° C. for 20 minutes).
[0175] In some embodiments, the emulsion of the application has the advantage that it is resistant to oxidation, has a long shelf-life and / or is stable at high temperature processing, thus allowing it to be heat-treated or sterilized. This is of great benefit as it allows the encapsulated one or more cannabinoid compounds of the application to be added to products that must be sterilized before consumption. Further, the application provides convenient formulations of cannabinoid compounds useful for enhancing or creating aqueous soluble cannabinoid compositions. The emulsion of the application may be useful, for example, to prepare compositions selected from a beverage, gel, gelatin and concentrate and as a beverage enhancer. As such, the emulsion of the application is for use in compositions selected from beverages, gels, gelatins and concentrates and as a beverage enhancer.
[0176] In some embodiments, the application also includes a method of making a liquid composition of the application comprising the emulsion of the present application comprising: diluting the emulsion of the application with a suitable liquid to form the composition. In some embodiments, the liquid composition of the application is homogeneous. In some embodiments, the liquid composition of the application is an emulsion. To prepare the liquid composition of the application, any dispersion / solubilization methods known in the art may be used. In some embodiments, the liquid used for dilution is selected from liquid selected from water, oil, alcohol, non-alcoholic drink, soft drink, fruit juice, vegetable juice, tea, coffee, milk and punch.
[0177] In some embodiments, the present application also includes a method of making a dry powder composition of the application comprising drying the emulsion of the application to form a powder. In some embodiments, the emulsion is dried by spray-drying. Alternative methods include, but are not limited to, pan coating, airsuspension coating, centrifugal extrusion, vibrational nozzle technique, freeze-drying or using a food dehydrator. As such, the application further includes a powder obtained by drying the emulsion of the present application.
[0178] In some embodiments, the resulting powder composition is mixed in a suitable liquid, solid, gel, cream, paste, or any other form, for administration tosubjects. In some embodiments, the powder composition is prepared and packaged using any packaging known in the art. For example, in some embodiments, the powder composition is packaged as a single serving or multiple servings in a metal, glass, or plastic container. In some embodiments, the powder composition may be packaged as a single serving stick pack or pouch.IV. Methods and Uses of the Emulsions
[0179] The emulsion of the application has the advantage that it is, for example, resistant to oxidation, has a long shelf-life and is stable at high temperature processing, thus allowing it to be heat-treated or sterilized. This is of great benefit as it allows the encapsulated cannabinoid compounds of the application to be added to products that must be sterilized before consumption. Further, the present application provides convenient formulations of cannabinoid compounds useful for enhancing or creating aqueous soluble cannabinoid compositions. The emulsion of the application may be useful, for example, to prepare compositions selected from a beverage, gel, gelatin and concentrate and as a beverage enhancer. As such, the present application includes a use of the emulsion of the application in compositions selected from beverages, gels, gelatins and concentrates and use as a beverage enhancer.
[0180] Therefore, the present application also includes a method of reducing the incidence and / or severity of a disease, disorder or condition in a subject comprising administering a composition of the application to a subject in need thereof.
[0181] The application also includes a use of a composition of the application to reduce the incidence and / or severity of a disease, disorder or condition.
[0182] In some embodiments, the compositions of the application improve resistance to the disease, disorder or condition and / or improve immune response. In some embodiments, the compositions of the application maintain or promote health, including nutrient structure-function and quality of life, so that the disease, disorder or condition is improved or not worsened. In some embodiments, the compositions of the application relieve symptoms of the disease, disorder or condition.
[0183] In some embodiments, the methods and the uses of the application improve resistance to the disease, disorder or condition and improve immune response relative to otherwise the same conditions in a subject, except that the subject is not administered a composition of the application. In some embodiments, themethods and the uses of the application maintain or promote health, including nutrient structure-function, to support the subject’s body’s own ability to resist the disease, disorder or condition and / or improve immune response. In some embodiments, the methods and uses of the application improvesquality of life or relieves symptoms of the disease, disorder or condition.
[0184] In some embodiments, the disease, disorder or condition is pain or inflammation or a combination thereof, or any disease, disorder or condition that results from pain or inflammation, or a combination thereof. In some embodiments, the compositions of the application reduce the incidence and / or severity of a disease, disorder or condition in a subject by improving the overall health of a subject for example by supporting the subject’s body’s own ability to reduce pain and / or inflammation.
[0185] In some embodiments, the disease, disorder or condition is Alzheimer's disease; Parkinson's disease; essential tremor; amyotrophic lateral sclerosis (ALS); Huntington's disease; Friedreich's ataxia; multiple sclerosis; frontotemporal dementia; prion disease; Lewy body dementia; progressive supranuclear palsy; vascular dementia; normal pressure hydrocephalus; traumatic spinal cord injury; human immunodeficiency virus (HIV) dementia; alcohol induced neurotoxicity; Down's syndrome; movement disorders ofthe central and / or peripheral nervous system; motor neurone diseases (MND); spinal muscular atrophy; or any other related neurological or psychiatric neurodegenerative disease; brain damage; brain injury; brain dysfunction; dysgraphia; dysarthria; apraxia; agnosia; amnesia; dizziness; vertigo; coma; stroke; spinal cord damage; spinal cord injury; spinal cord disorders; central neuropathy; peripheral neuropathy; cranial nerve disorder; trigeminal neuralgia; tumors of the nervous system; infections of the brain or spinal cord; encephalitis; meningitis; prion disease; complex regional pain syndrome; an autonomic nervous system disorder; autonomic neuropathy; dysautonomia; postural orthostatic tachycardia syndrome (POTS); neurocardiogenic syncope (NCS); multiple system atrophy (MSA); hereditary sensory and autonomic neuropathy (HSAN); Holmes-Adie syndrome (HAS); a sleep disorder; narcolepsy; pain such as acute pain and chronic pain; migraine; cluster headache; tension headache; joint pain, back pain; lower back pain; neck pain; neuropathic pain; cancer pain; allodynia; osteoarthritic pain; inflammatory pain; a neuropsychiatric disorder; attention deficit hyperactivity disorder;autism; Tourette's Syndrome; obsessive compulsive disorder; an autism spectrum disorder; Rett syndrome; Fragile X syndrome; Angelman syndrome; hyperkinetic disorder; Tourette syndrome; dystonia; a cancer; brain cancer; glioma; breast cancer; liver cancer; lung cancer; pancreatic cancer; melanoma; ovarian cancer; gastric cancer; renal cancer; bladder cancer; addiction; nicotine addiction; smoking; alcohol addiction; drug addiction; Cannabis use disorder; a mental disorder; post-traumatic stress disorder; anxiety; early psychosis; schizophrenia; a cognitive disorder; stroke; cardiac ischemia; coronary artery disease; thromboembolism; myocardial infarction; ischemic related disease; a gastrointestinal disorder; inflammatory bowel disease; Crohn's disease; ulcerative colitis; nausea; vomiting; emesis; motion sickness; chemotherapy induced nausea; chemotherapy induced nausea vomiting; inflammation; arthritis; rheumatoid arthritis; osteoarthritis; diabetes; high blood pressure; poor insulin control; appetite suppression; anorexia; neonatal hypoxic- ischemic encephalopathy (NHIE); a degenerative skeletal muscle disease; or Duchenne muscular dystrophy (DMD).
[0186] In some embodiments, the subject is a mammal. In some embodiments, the subject is human.
[0187] In some embodiments, the disease, disorder or condition is joint pain. In some embodiments, the disease, disorder or condition is inflammatory pain. In some embodiments, the disease, disorder or condition is osteoarthritic pain.
[0188] In some embodiments, the methods and uses of the application reduce the intensity or duration of pain or eliminate the pain in a subject in need thereof.
[0189] In some embodiments, the methods and uses of the application provide improved bioavailability of the one or more cannabinoid compounds and fast pain relief.
[0190] In some embodiments, the methods and uses of the application achieve reduced pain intensity for at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 18 hours, or at least 24 hours post administration.
[0191] Treatment methods of the application comprise administering to a subject a therapeutically effective amount of a composition of the application and optionally administered once, twice, three, or four times a day, or as needed.
[0192] In some embodiments, the composition of the application is administered orally.
[0193] In some embodiments, the composition of the application is administered in a liquid form. In some embodiments, the liquid form is a solution, suspension or emulsion.
[0194] The methods of preparing the composition of the application are as specified above.
[0195] The following non-limiting examples are illustrative of the present application:EXAMPLESMethod, Equipment and MaterialsEquipmentTable 1 : Equipment used
[0196] The particle size was determined using dynamic light scattering (DLS) method. The sample was diluted 1 :2500 with acidic water solution (the solution was prepared by adding anhydrous citric acid to Type 1 deionized water to obtain pH 3.2). The test was performed according to Anton Paar Litesizer500 instructions, and further dilutions were performed as needed and indicated by the instrument.MaterialsMaterials Used: CBG isolate, sunflower oil, omega 3, water, whey protein, sodium caseinate, KOH, citric acid, anti-foaming agent.StandardsTable 2: Standards Used for QuantitationInitial Batch
[0197] The initial batch, Lot LC-NPMC-2022-04-18-1-B&B, was prepared in the lab according to the process developed by the Applicant with particle size reduction using the microfluidizer at several different pressures and number of passes.
[0198] The process developed by the Applicant included: 1) mixing caseinate protein and whey protein complex in water and allowing dissolution at room temperature for about 1 hour; 2) adjusting the pH with KOH to 6.5-8; 3) heating the aqueous solution of casein protein and whey protein at about 90 °C for 5 to 10 min; 3) cooling the protein complex solution to about 10 °C; 4) adjusting the pH of the protein complex solution with citric acid anhydrous to pH of about 3.2; 5) adding oil to the protein complex solution under high shear mixing (handheld, 12-15 krpm for 3 min.) 6) heat treating the mixture at 95 °C for 3 sec. ; and 7) homogenizing the mixture in two stages using a microfluidizer at 3000 psi and 500 psi pressure.Table 3: Emulsion Composition for Initial BatchesTable 4: Particle Size (nm) and Zeta Potential (mV) of the Initial Batches
[0199] The target particle size should be in the nano range (sub-micron); close to 500 nm. The target zeta potential should optimally be more than 30 mV (or less than -30 mV). Zeta potential is an indicator of stability of the colloidal system. Colloids with zeta potential of more than 30 mV (or less than -30 mV) are repelled from one another and remain well dispersed or easily redispersed in solution. As shown in Table 4 and Table 5, all trials resulted in particle size relatively close to 500 nm and zeta potential greater than 30 mV. Therefore, it was demonstrated that the emulsion had successfully been recreated.
[0200] The stability of the initial batch emulsion was monitored by taking particle size over a period of 18 days as shown in Figure 1 .
[0201] Particle size of the initial batch emulsions was measured at 8 and 18 days. There was no visible phase separation seen in any of the emulsions throughout the duration of the testing.
[0202] Particle size for each emulsion remained in the nano range; all under 750 nm except the 3000 psi 1stpass sample. Visible mold / bacteria began to form after the 18-day mark interfering with particle size measurements and subsequent testing was not performed.Experimental Batch
[0203] A second batch, Lot LC-NPMC-2022-04-29-1-B&B, was made using the emulsion composition of Table 3 above, varying the pressures on the microfluidizer. Pressure was set for 3000 and 5000 psi to investigate if target particle size could be achieved and remain stable using lower energy for emulsification.Table 5: Particle Size (nm) and Zeta Potential (mV) of Batch Lot LC-NPMC-2022-04- 29-1-B&B
[0204] As shown in Table 5, particle size and zeta potential for all preparations met target values, suggesting that all of the prepared emulsions would remain stable.As per the initial batch, the experimental batch was tracked over time to monitor the change in particle size.
[0205] As can be seen in Figure 5, the emulsions had only slight increase in particle size after one week with an increase of less than 150 nm. The emulsions were to be monitored for another week however similarly to the initial batch, mold / bacteria began to grow after the 7-day mark, interfering with any future particle size measurements. A pasteurization step was added for all future emulsions to mitigate microbial growth.Buffer Dilution Study
[0206] A dilution of each emulsion sample was performed for analysis to reduce the density of particles to measure laser light scattering angles through the solution. A low concentration pH citrate buffer was employed to avoid destabilization of the colloids during the test procedure. Various buffer concentrations were prepared to investigate the effect of ionic strength and pH on particle size measurement.Table 6: Particle Size (nm) Measurements of 3000 psi, 1st Pass Sample from Initial Batch LC-NPMC-2022-04-18-1-B&BTable 7: Particle Size (nm) Measurements of 10000 psi, 2ndPass Samples fromInitial Batch over Two Days
[0207] As can be seen in Table 6 and Table 7, two emulsions from the initial batch were tested using four different diluents for particle size testing. Target pHs of2.00 and 3.20 were proposed matching the pH of the finished formulation. Diluent concentration was varied between 20 mM and 50 mM.
[0208] LC-NPMC-2022-04-18-1 -B&B that was submitted to 1 pass at 3,000 psi had consistent results with all of the diluent buffers with the exception of 50 mM at pH 2.50.
[0209] LC-NPMC-2022-04-18-1 -B&B that was submitted to 10,000 psi and 2 passes also showed little variation across all of the buffer solutions except for one outlier with the diluent of 50 mM and a pH of 3.15. LC-NPMC-2022-04-18-1 -B&B was stored overnight in the diluent and tested again the next day. Testing the next day revealed a slight increase in particle size.
[0210] The outlier from each emulsion sample occurred with higher ionic strength buffers. This did not occurforthe 10,000 psi sample the second day of testing. The remaining samples did not vary much in particle size suggesting that the ionic strength is not a critical parameter of the diluent as long as the pH is below 3.20.Design of Experiment (DOE) Batches
[0211] To better understand the effects of the manufacturing parameters and ingredient ratios on emulsion stability a DOE was performed. The DOE batches were evaluated on particle size, change in particle size over two weeks, zeta potential, change in zeta potential over two weeks, separation time, viscosity and change in pH.Table 8: DOE Plan to Evaluate Effect of Manufacturing Parameters and Ingredient Ratios on Emulsion Stability
[0212] A half factorial DOE design was chosen varying four parameters (whey, casein, microfluidizer pressure and the presence of KOH) while keeping the remainingparameters the same as the original tech transfer batches. It was decided that a resolution of IV was acceptable to be able to grasp the effect of the parameters on the final emulsion, resulting in a total of eight experiments. A resolution of IV allowed the estimation of main effects caused by parameters unconfounded by two-factor Interactions.DOE Results
[0213] The DOE batches were created over the course of two days, formulated in the same order as listed in Table 8. The initial protocol included the use of an overhead mixer to create a coarse emulsion, however, this method of mixing did not provide enough shear force to make the input coarse emulsion. A planned deviation to the protocol was documented to include the use of a blender.Table 9: Emulsion Composition of B&BDOEBATCH-1Table 10: Emulsion Composition of B&BDOEBATCH-2Table 11 : Emulsion Composition of B&BDOEBATCH-3| Total | 1OO.OO | 511.07 |Table 12: Emulsion Composition of B&BDOEBATCH-4Table 13: Emulsion Composition of B&BDOEBATCH-5Table 14: Emulsion Composition of B&BDOEBATCH-6Table 15: Emulsion Composition of B&BDOEBATCH-7Table 16: Emulsion Composition of B&BDOEBATCH-8
[0214] General trends were observed while creating the emulsions for the DOE experiment. The batches that contained the lowest amount of whey and casein (batches 1 and 7) took very little time to dissolve the proteins. Additionally, very little citric acid was needed to acidify the solution as the pH was considerably lower, -2.60, after addition of the full amount as per the recipe. The viscosity of both of these batches was quite low when compared to the previously made placebo batches as part of the tech transfer. The batches containing the highest amount of whey and casein, batch 4 and 8, took longer to dissolve the proteins when compared to the other DOE batches. The amount of citric acid required to acidify the solution was more when compared to the other batches, with approximately 9 g being added. The viscosity of batches was higher than the tech transfer batches, making the batches difficult to work with and process through the microfluidizer. The emulsions that were prepared without the addition of potassium hydroxide, batches 5 - 8, demonstrated no difference in processing when compared to batches containing potassium hydroxide. The lack of potassium hydroxide did not appear to add to the difficulty of dissolving the proteins and did not contribute to an increase in production time.
[0215] Effect charts were made to evaluate the individual and combined relative effect of input ingredient component concentrations. As can be seen in Figure 3 through Figure 7, the Pareto charts rank the parameters by order of effect with the parameter showing the largest effect at the top and the parameter with the lowest effect at the bottom. Parameters with no effect are not shown on the chart. The dotted line on the chart determines the threshold for which a parameter is deemed significant by the Minitab software. Only one of the investigated parameters had a significant effect. As seen in Figure 4, the concentration of casein was shown to have a significant effect on zeta-potential of the emulsion.Table 17: Results of DOE Batches Highlighting %Casein
[0216] As can be seen in Table 17, the casein concentration was determined to have an effect on the zeta potential. A high casein content was linked to a zeta potential of ~17 mV while a low casein content was linked to a zeta potential of ~21 mV. There were no other significant effects from any parameters or combination of parameters that were found for the evaluated criteria.
[0217] The values for particle size and zeta-potential for the DOE batches were different from the tech transfer batches Lot LC-NPMC-2022-04-18-1-B&B and Lot LC- NPMC-2022-04-29-1 -B&B. Particle size was larger and zeta-potential was lower in the DOE batches. The reason for these differences was discovered to be caused by the buffer system used as a diluent to conduct the measurements. It was discovered that the buffer used, contained an ion concentration that was too elevated, leading to an electrical current which overwhelmed the Instrument (see next section).Cannabigerol (CBG) Containing EmulsionsFirst CBG Batches
[0218] Emulsions containing CBG isolate were created to investigate the effect of the presence of cannabinoids on emulsion stability. An anti-foaming agent was also added to minimize the foaming of proteins during emulsion processing. A total of 4 batches were created, varying the composition as shown in the tables below.Table 18: Emulsion Composition of 20Jul2022-Batch1Table 19: Emulsion Composition of 20Jul2022-Batch2Table 20: Emulsion Composition of 20Jul2022-Batch3Table 21 : Emulsion Composition of 20Jul2022-Batch4Table 22: Particle Size and Zeta Potential Results from CBG Batches Made July 20, 2022
[0219] CBG was dissolved in sunflower oil via mechanical stirring using a stirring bar. Upon even dispersion of the isolate solids, the mixture was placed in an ultrasonic bath at 80 kHz at 100 % power for 10 minutes to ensure the mixture was homogenous.
[0220] The particle size of the CBG containing emulsions (Table 23) were similar to those of previous placebo formulations (formulations without CBG). The zeta potential was less than ideal, with each batch reporting a zeta potential less than 20 mV. Upon further investigation, it was discovered that the ion concentration of the buffer system being used was too high, not allowing the instrument to reach peak voltage and properly gauge the zeta potential. This was rectified in future zeta potential measurements by returning to the citric acid solution, of a lower ionic strength and with a pH of ~3.2 as was used in earlier measurements.
[0221] The batches relative to each other showed very little difference in zeta potential between batches and little difference in particle size with exception to batch 1. The difference between batch 1 and the remaining batches was likely due to a slightly different microfluidization pressure used. The pressure was increased to facilitate easier processing of the emulsion through the instrument. The results indicate that there is little to no effect on particle size when potassium hydroxide is omitted orupon the addition of the anti-foaming agent. A second CBG batch was prepared to determine the effect of CBG on emulsion stability with the knowledge in hand to obtain proper zeta potential measurements.Second CBG Batches
[0222] The second CBG batches were created to determine if the CBG containing emulsion is stable. A secondary objective of the batches was to use a new brand of sodium caseinate and to ensure that stability was not affected with the new product.Table 23: Emulsion Composition of 11Aug2022-Batch1Table 24: Emulsion Composition of 11Aug2022-Batch2Table 25: Emulsion Composition of 11Aug2022-Batch3Table 26: Particle Size and Zeta Potential Results from CBG Batches Made August 11 , 2022
[0223] The batches were divided prior to the addition of oil. One portion contained oil only and the other contained the oil / CBG blend. As shown in Table 23, Table 24 and Table 25, batch 1 was made with the original casein, batch 2 was made with the new casein and the anti-foaming agent and batch 3 was made with the new casein and no anti-foaming agent. Particle size and zeta potential measurements as reported in Table 26 were well within the established target ranges. There was no visible difference between the formulations. In conclusion, CBG, casein source and presence of anti-foaming agent was shown to have little impact on particle size and zeta potential.Method Extraction Pre-Validation for Potency Analysis
[0224] A batch with the same composition as the batch seen in Table 24, MethodValidation-Batchl and replacing the sunflower oil for omega-3 enriched algal oil was made to validate the capability of the LC-NPMC-MTH-001 potency analysis method with the emulsion sample matrix. A separate placebo batch, not containing CBG, was also created to investigate the interference created by the sample matrix on the high-performance liquid chromatography HPLC.
[0225] The Bligh and Dyer extraction method [Breil, C., Abert Vian, M., Zemb, T., Kunz, W., & Chemat, F. (2017). “Bligh and dyer” and Folch methods for solid- liquid-liquid extraction of lipids from microorganisms. Comprehension of solvatation mechanisms and towards substitution with alternative solvents. International Journal of Molecular Sciences, 18(4), 708] was utilized to separate the oil containing CBG from the remaining components of the emulsion. Traditionally used in biochemistry to separate lipids from biological tissues, this method proved effective at extracting the CBD / oil mixture from the emulsion. The method entails the extraction of the emulsion using first a mixture of chloroform and methanol, followed by two subsequentextractions with chloroform and then with water. The solution was then centrifuged to separate the aqueous and organic layers with a layer of proteins in between.
[0226] The potency analysis method was validated for selectivity, recovery, and repeatability. An assay was also run on the CBG isolate to test for purity. The selectivity was verified by ensuring the resolution between the CBG and Cannabigerolic acid (CBGA) peaks were greater than one. Recovery was accessed based on the amount of CBG that was quantified from placebo emulsions spiked with a known amount of CBG. The repeatability of the method was evaluated by verifying the %RSD of three spiked emulsions was less than two percent. The standard used for the quantification of cannabinoids in the emulsion was a combination of CBG and CBGA single component standards, made to a concentration of 50 ppm for each component.Peak Area Study
[0227] The results of the method validation study yielded concentrations for the positive controls, spiked placebo emulsion and CBG containing emulsion that were higher than expected. This was thought to have occurred due to the fact that the peaks for CBG and CBGA are located close together on the chromatograms. This would lead to an increased peak area as the software would integrate a portion of the baseline of the adjacent peak. This was verified by conducting a separate study to investigate if the peak area of CBG was larger when accompanied by CBGA. Four standards were prepared for the study; two containing CBG and CBGA while the remaining two contained solely CBG. These standards were prepared from two individual stock standards, one containing solely CBG and the other containing solely CBGA.T able 27 : Peak Areas of CBG Vs CBG + CBGA
[0228] As can be seen in Table 27, the peak areas corresponding to CBG of the standard containing both components are larger than the standard containing onlyCBG. These results suggest that the combination of standards could have had an effect on the CBG peak areas observed during the method validation study.Method Validation Results
[0229] Taking into consideration the findings of the peak area study, the standards were not used to calculate the concentration of each emulsion. The ratio of peak areas of the positive control, CBG isolate dissolved in methanol for a target concentration of 50 ppm, to the peak areas of the samples was utilized to calculate the concentration of the emulsions.
[0230] Placebo emulsion samples were tested to determine if there was any interference in the chromatogram caused by the sample matrix. Negative control samples were found to have no considerable matrix interference, as can be seen in Figure 8, with no visible peaks being present.Table 28: Results from CBG Emulsion Samples
[0231] The CBG containing emulsions were tested to determine the recovery of the method as well as the reproducibility of the overall extraction and potency determination. The maximum possible concentration of the CBG containing emulsion is -12.43 mg of CBG per gram of oil, according to the master batch record. The recovery of CBG from the emulsions was determined to be -94.3 % as can be seen in Table 28.Table 29: Results from CBG Spiking of Placebo Emulsions
[0232] The spiked placebo emulsions were tested according to the extraction method in order to estimate the recovery of the method. As can be seen in Table 29, the recovery of CBG from the spiked emulsions was found to be higher than expected.This is likely due to the concentration of CBG in the oil not being known with certainty. The concentration of CBG to oil was estimated based on the oil added during emulsion preparation. This could be rectified by exploring a different method for spiking where the amount of oil into which the CBG isolate is being spiked is known.CBG Load Study
[0233] The load capability of the CBG in the emulsion was examined along with short-term stability results for potency and particle size.
[0234] The emulsions were prepared as described above while varying the content of CBG.Table 30: Emulsion Batch Record for 50 mg per Beverage TargetTable 31 : Emulsion Batch Record for 100 mg per Beverage TargetTable 32: Emulsion Batch Record for 210 mg per Beverage TargetTable 33: Emulsion Batch Record for 420 mg per Beverage Target
[0235] As can be seen in Table 30, Table 31 , Table 32 and Table 33, the CBG concentrations were varied to simulate a beverage containing 50 mg, 100 mg, 210 mg and 420 mg respectively. This is to say that the beverages would contain 50, 100, 210, and 420 mg per beverage if the emulsions were to be diluted in the final beverage. The 50 to 210 mg batches were made successfully without the need for added sonication. The 420 mg batch was not successful as the amount of CBG could not be fully dissolved in the oil.
[0236] A deviation from the procedure was documented to include pasteurization (in glass bottles) at 70 °C for 30 minutes. Pasteurization was successful; there was no visible bacterial growth after two weeks.Two Week Particle Size and Zeta PotentialTable 34: Particle Size and Zeta Potential Data for Load Study Emulsions Collected over Two Weeks
[0237] Particle size and zeta potential were monitored for all three concentrations as shown in T able 34 for a period of almost three weeks stored at 25°C. Particle size for all three batches remained stable, with all samples varying less than 60 nm from the initial measurement. Zeta potential remained at the desired target of > 30 mV, indicating emulsion stability. A visual inspection concluded that there was no creaming or separation observed. The emulsions maintained homogeneous appearance over the study period.Two Week PotencyThe potency of the load study emulsions was tested for two weeks under ambient conditions (25°C). The results are shown in tables 36-37 below.Table 35: Concentration of Load Study Emulsions According to Input from Master Batch RecordsTable 36: Average Potency (% label claim): One Week StabilityTable 37: Average Potency (% label claim): Two Weeks Stability
[0238] The time zero data, not displayed in this report, was compromised due to incorrect dilutions being used for analysis. The time zero concentrations, as can be seen in Table 35, were instead estimated from the material inputs as per the MBR.
[0239] After one week, the 50 mg / beverage batch performed the best, retaining ~90 % potency as can be seen in Table 36. The emulsions with higher concentration showed ~84 % and ~72 % potency retention for the 100 mg and 210 mg per beverage batches, respectively. Testing the potency after two weeks lead to all three batches decreasing in potency further with ~79 %, ~79 % and ~65 % remaining for the 50 mg, 100 mg, and 210 mg per beverage batches, respectively.Stability of the Emulsion
[0240] The emulsion was prepared containing 3% sodium caseinate, 3% whey protein, 0.58% citric acid, 15% omega-3 oil, 0.02% anti-foaming agent, and the remainder was water. 10% KOH solution was used in an amount appropriate to achieve pH of 7.5-8 in the aqueous solution of casein protein and whey protein complex. The emulsion was sampled after pasteurization and was tested for stability in the stability chamber at 25°C / 60% relative humidity (RH) and at 4°C to gather information from both conditions. All samples were initially subjected to 24 hours of 25°C / 60%RH conditions. rnnoziii Particle Size & Zeta PotentialTable 38: Particle size and zeta potential for samples stored for four weeks under 25 °C and 4 °C
[0242] The emulsion displayed good zeta potential values across the 4-week duration under both storage conditions. It can be seen in Table 38 that all zeta potential values are >|30| mV, an indicator of physical stability (Mahbubul, I. (2019). 3 - Stability and Dispersion Characterization of Nanofluid. In Preparation, Characterization, Properties and Application of Nanofluid (pp. 47-112). William Andrew Applied SciencePublishers.). The particle size for both the ambient and refrigerated samples remained in the nanoparticle range. The refrigerated sample was stable with an overall change of only -10%, but the particle size did increase rapidly after the 2-week time point in ambient storage conditions. This was expected as higher temperatures decrease the viscosity of the oil and increase the collisions between droplets (Adhikary, T., & Basak, P. (2022). Chapter 27 - Extraction and separation of oils: the journey from distillation to pervaporation. In Advances in Oil-Water Separation (pp. 511-535).Conclusion
[0243] Throughout the duration of the project, a successful CBG containing emulsion was demonstrated. The placebo emulsion was shown to have excellent stability through the use of particle size and zeta potential data (stored for four weeks at room temperature and 4 °C). A DOE type experiment was carried out to investigate the effect of different ingredients on emulsion stability parameters. The DOE revealed that the lone effect of significance observed was the effect of casein concentration on the zeta potential. The cannabinoid CBG was successfully incorporated into the emulsion formulation as well as a defoaming agent to reduce air being introduced into the system. The stability of the CBG containing emulsion was demonstrated through particle size and zeta potential data. The method for cannabinoid potency analysis was validated by testing for selectivity, recovery, and repeatability. An extraction method known as the Bligh and Dyer method was implemented for recovering the CBG containing oil from the emulsion. An omega-3 rich, algal based oil was incorporated into the formulation and was demonstrated to create a successful emulsion using this ingredient. A CBG load study resulted in excellent particle size and zeta potential data for every concentration tested. The potency analysis of the load study emulsions demonstrated reduced potency retention in emulsions with higher CBG concentrations.
Claims
CLAIMS:1 . An emulsion comprising: a) one or more cannabinoid compounds; b) a complex of whey protein and casein protein; c) water; and d) an oil.
2. The emulsion of claim 1 , wherein the one or more cannabinoid compounds are selected from cannabigerolic acid (CBGA), cannabigerolic acid monomethylether (CBGAM), cannabigerol (CBG), cannabigerol monomethylether (CBGM), cannabigerovarinic acid (CBGVA), cannabigerovarin (CBGV), cannabichromenic Acid (CBCA), cannabichromene (CBC), cannabichromevarinic acid (CBCVA), cannabichromevarin (CBCV), cannabidiolic acid (CBDA), cannabidiol (CBD), A6 cannabidiol (A6-CBD), cannabidiol monomethylether (CBDM), cannabidiol-C4 (CBD C4), cannabidivarinic acid (CBDVA), cannabidivarin (CBDV), cannabidiorcol (CBD C1), tetrahydrocannabinolic acid A (THCA-A), tetrahydrocannabinolic acid B (THCA- B), tetrahydrocannabinol (THC or A9-THC), A8-tetrahydrocannabinol (A8-THC), A10- tetrahydrocannabinol (A10-THC), tetrahydrocannabinolic acid C4 (THCA-C4), tetrahydrocannbinol C4 (THC C4), tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabivarin (THCV), A8-tetrahydrocannabivarin (A8-THCV), A9 tetrahydrocannabivarin (A9-THCV), tetrahydrocannabiorcolic acid (THCA-C1), tetrahydrocannabiorcol (THC-C1), delta 7 cis iso tetrahydrocannabivarin, A8 tetrahydrocannabinolic acid (A8-THCA), A9 tetrahydrocannabinolic acid (A9-THCA), cannabicyclolic acid (CBLA), cannabicyclol (CBL), cannabicyclovarin (CBLV), cannabielsoic acid A (CBEA-A), cannabielsoic acid B (CBEA-B), cannabielsoin (CBE), cannabinolic acid (CBNA), cannabinol (CBN), cannabinol methylether (CBNM), cannabinol-C4 (CBN-C4), cannabivarin (CBV), cannabino-C2 (CBN-C2), cannabiorcol (CBN-C1), cannabinodiol (CBND), cannabinodivarin (CBDV), cannabitriol (CBT), 11 hydroxy-A9-tetrahydrocannabinol (11 OH-THC), 11 nor 9-carboxy-A9- tetrahydrocannabinol ethoxy-cannabitriolvarin (CBTVE), 10 ethoxy-9-hydroxy-A6a- tetrahydrocannabinol, cannabitriolvarin (CBTV), 8,9 dihydroxy-A6a(10a)- tetrahydrocannabinol (8,9-Di-OH-CBT-C5), dehydrocannabifuran (DCBF), cannbifuran (CBF), cannabichromanon (CBCN), cannabicitran (CBT), 10 oxo- A6a(10a)-tetrahydrocannabinol (OTHC), A9-cis-tetrahydrocannabinol (cis-THC), cannabiripsol (CBR), 3,4,5,6-tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n-propyl-2,6-methano-2H-1-benzoxocin-5-methanol (OH-iso-HHCV), and trihydroxy- delta-9-tetrahydrocannabinol (triOH-THC), or any combination thereof.
3. The emulsion of claim 1 or 2, wherein the one or more cannabinoid compounds are comprised in a distillate, an isolate, cannabis oil, cannabis extract or a combination thereof.
4. The emulsion of claim 3, wherein the one or more cannabinoid compounds are comprised in a distillate.
5. The emulsion of claim 3, wherein the one or more cannabinoid compounds are comprised in an isolate.
6. The emulsion of claim 3, wherein the one or more cannabinoid compounds are comprised in a cannabis oil.
7. The emulsion of claim 3, wherein the one or more cannabinoid compounds are comprised in a cannabis extract.
8. The emulsion of any one of claims 1 to 7, wherein the one or more cannabinoid compounds is or comprises CBG, or a salt, isomer, enantiomer, or optically active derivative thereof.
9. The emulsion of claim 8, wherein the one or more cannabinoid compounds is or is comprised in a CBG distillate.
10. The emulsion of claim 8, wherein the one or more cannabinoid compounds is or is comprised in a CBG isolate.
11. The emulsion of any one of claims 1 to 7, the one or more cannabinoid compounds is or comprises CBD, or a salt, isomer, enantiomer, or optically active derivative thereof.
12. The emulsion of claim 11 , wherein the one or more cannabinoid compounds is or is comprised in a CBD distillate.
13. The emulsion of claim 11 , wherein the one or more cannabinoid compounds is or is comprised in a CBD isolate.
14. The emulsion of any one of claims 1 to 7, wherein the one or more cannabinoid compounds is or comprises THC, or a salt, isomer, enantiomer, or optically active derivative thereof.
15. The emulsion of claim 14, wherein the one or more cannabinoid compounds is or is comprised in a THC distillate.
16. The emulsion of claim 14, wherein the one or more cannabinoid compounds is or is comprised in a THC isolate.
17. The emulsion of any one of claims 1 to 16, wherein the one or more cannabinoid compounds are present in the emulsion in an amount of about 0.25 wt% to about 13 wt% of the emulsion.
18. The emulsion of any one of claims 1 to 17, wherein the emulsion further comprises one or more terpenes, one or more terpenoids, one or more flavonoids, and any combinations thereof.
19. The emulsion of claim 18, wherein the emulsion further comprises one or more terpenes and / or one or more terpenoids.
20. The emulsion of claim 19, wherein the one or more terpenes and / or one or more terpenoids are present in the emulsion in an amount of about 0 to about 13 wt% of the emulsion.21 . The emulsion of any one of claims 1 to 20, wherein the whey protein is selected from whey protein isolate, whey protein concentrate, a-lactalbumin and p-lacoglobulin.
22. The emulsion of claim 21 , wherein the whey protein is whey protein isolate.
23. The emulsion of any one of claims 1 to 22, wherein the casein protein is selected from a-casein, K-casein, p-casein, b-casein, and their salts, such as sodium, potassium, calcium and ammonium, or mixtures thereof.
24. The emulsion of claim 23, wherein the casein protein is sodium caseinate.
25. The emulsion of claim 21 or 22, wherein the whey protein is present in the emulsion in an amount of about 0.25 wt% to about 5 wt% of the emulsion.
26. The emulsion of claim 23 or 24, wherein the casein protein is present in the emulsion in an amount of about 0.25 wt% to about 5 wt% of the emulsion.
27. The emulsion of any one of claims 21 to 26, wherein the weight ratio of casein protein to whey protein is about 10:1 to about 1 :10.
28. The emulsion of any one of claims 25 to 27, wherein the whey protein is present in the emulsion in an amount of about 1 .3 wt% and the casein protein is present in the emulsion in an amount of about 1 .3 wt%.
29. The emulsion of any one of claims 1 to 28, wherein the complex comprises whey protein and casein protein which are cross-linked or covalently bonded.
30. The emulsion of any one of claims 1 to 29, wherein the one or more cannabinoid compounds are encapsulated in the complex of whey protein and casein protein.31 . The emulsion of any one of claims 1 to 30, wherein the water is present in the emulsion in an amount of about 65 wt% to about 80 wt% of the emulsion.
32. The emulsion of any one of claims 1 to 31 , wherein the oil is omega-3 oil.
33. The emulsion of claim 32, wherein the omega-3 oil is selected from oils obtained from fish such as salmon, tuna, herring, mackerel, anchovies, sardines, pollock, cod, catfish, flounder, grouper, halibut, mahi mahi, orange roughy, red snapper, shark, swordfish, tilefish, plankton, algae and / or krill, green-lipped mussel, and / or plant oils such as canola oil, borage oil, evening primrose oil, safflower oil, sunflower oil, flaxseed oil, wheat germ oil, algal oil, and / or grapeseed oil, and / or oils obtained from chia seeds, kiwifruit seeds, perilla seeds, lingonberry seeds, camelina seeds, purslane seeds, black raspberry seeds, hemp seeds, butternut, walnuts, pecan nuts and / or hazel nuts.
34. The emulsion of claim 33, wherein, the oil is sunflower oil.
35. The emulsion of claim 33, wherein the oil is algal oil.
36. The emulsion of any one of claims 32 to 35, wherein the oil is present in the emulsion in an amount of about 8 wt% to about 30 wt% of the emulsion.
37. The emulsion of any one of claims 32 to 35, wherein the weight ratio of oil to one or more cannabinoid compounds is about 100:1 to about 1 :1 .
38. The emulsion of any one of claims 1 to 37, wherein the emulsion further comprises one or more pH adjusting agents selected from sodium acetate, phosphoric acid, acetic acid, lactic acid, fumaric acid, adipic acid, malic acid, tartaric acid, citric acid, hydrochloric acid, sulfuric acid, potassium hydroxide, salts thereof, and combinations thereof.
39. The emulsion of claim 38, wherein the one or more pH adjusting agents comprise citric acid and potassium hydroxide.
40. The emulsion of claim 38 or 39, wherein the one or more pH adjusting agents are present in the emulsion in an amount of about 0.1 wt% to about 5 wt% of the emulsion.
41. The emulsion of any one of claims 1 to 40, wherein the emulsion further comprises one or more anti-foaming agents.
42. The emulsion of claim 41 , wherein the one or more anti-foaming agents are present in the emulsion in an amount of about 0.005 wt% to about 0.1 wt % of the emulsion.
43. The emulsion of any one of claims 1 to 42, wherein the emulsion has an average particle size of below about 1000 nm.
44. The emulsion of any one of claims 1 to 43, wherein the emulsion is stable at room temperature for at least two weeks or for at least three weeks.
45. The emulsion of any one of claims 1 to 44, wherein the emulsion has zeta potential of above about 30 mV.
46. The emulsion of claim 1 comprising: a) about 0.25 wt% to about 13 wt% of one or more cannabinoid compounds; b) about 0.25 wt% to about 5 wt% of casein protein; c) about 0.25 wt% to about 5 wt% of whey protein; d) about 8 wt% to about 30 wt% oil; e) optionally about 0.1 wt% to about 5 wt% of one or more pH adjusting agents; f) optionally about 0.005 wt% to about 0.1 wt % of one or more anti-foaming agents; and g) water to make 100%.
47. The emulsion of claim 46 comprising: a) about 1 wt% to about 12 wt% of one or more cannabinoid compounds; b) about 0.8 wt% to about 2 wt% of casein protein; c) about 0.8 wt% to about 2 wt% of whey protein; d) about 8 wt% to about 22 wt% oil;e) optionally about 2 wt% to about 5 wt% of one or more pH adjusting agents; f) optionally about 0.005 wt% to about 0.1 wt % of one or more anti-foaming agents; and g) water to make 100%.
48. The emulsion of claim 47, comprising: a) about 1 wt% to about 12 wt% of one or more cannabinoid compounds; b) about 1 .3 wt% of casein protein; c) about 1 .3 wt% of whey protein; d) about 8 wt% to about 22 wt% oil; e) optionally about 2 wt% to about 5 wt% of one or more pH adjusting agents; f) optionally about 0.005 wt% to about 0.1 wt % of one or more anti-foaming agents; and g) water to make 100%.
49. The emulsion of any one of claims 1 to 48 for use in a powder formulation.
50. A powder formulation which comprises the emulsion of any one of claims 1 to 48.51 . The emulsion of any one of claims 1 to 49 for use in compositions selected from beverages, gels, gelatins and concentrates and as a beverage enhancer.
52. A use of the emulsion of any one of claims 1 to 49 in compositions selected from beverages, gels, gelatins and concentrates and use as a beverage enhancer.
53. A composition selected from a beverage, gel, gelatin, concentrate and beverage enhancer, wherein the composition comprises the emulsion of any one of claims 1 to 49.
54. The composition of claim 53, wherein the composition is beverage.
55. The composition of claim 54, wherein the beverage is selected from water, milk, tea, coffee, fruit juice (e.g., orange, apple, cranberry, pear, currant, etc.), vegetable juice (e.g., carrot, tomato, etc.), nutritional supplement, natural health product, punch and carbonated drink (e.g. sparkling water, soda water, sports drink, and soft drink, such as a cola).
56. The composition of claim 55, wherein the beverage is the nutritional supplement or the natural health product.
57. The composition of any one of claims 53 to 56, wherein the one or more cannabinoids are present in the composition at a concentration of about 0.001 mg / ml to about 5 mg / mL.
58. The composition of claim 57, wherein the one or more cannabinoids are present in the composition in an amount of about 10 mg to about 500 mg.
59. The composition of any one of claims 53 to 58, wherein the composition further comprises a liquid selected from water, oil, alcohol, non-alcoholic drink, soft drink, fruit juice, vegetable juice, tea, coffee, milk and punch.
60. The composition of claim 59, wherein the liquid is present in the composition in an amount of between about 50% wt% to about 99.99% wt% of the composition.61 . The composition of claim 59 or 60, wherein the liquid is water.
62. The composition of any one of claims 53 to 61 , wherein the composition comprises between about 0.5% wt% to about 25% wt% of the emulsion.
63. The composition of any one of claims 53 to 62, wherein the composition comprises one or more of additives selected from anti-foaming agents, stabilizers, viscosity modifiers, emulsifiers, oils, thickening agents, minerals, acids, bases, vitamins, flavours, colourants, sweeteners, or combinations thereof.
64. The composition of claim 63, wherein the composition comprises the stabilizer.
65. The composition of claim 64, wherein the stabilizer is pectin.
66. The composition of claim 65, wherein the pectin is present in the composition in an amount of between about 0.1 % wt% to about 5% wt% of the composition.
67. The composition of any one of claims 53 to 66, wherein the composition further comprises at least one nutritional supplement selected from vitamin A, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K calcium, phosphorus, potassium, sulfur, sodium, chlorine, magnesium, iron, cobalt, copper, zinc, molybdenum, iodine, selenium, manganese, nickel, chromium, fluorine, boron, strontium histidine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, threonine, tryptophan, valine,alpha-linoleic acid, linoleic acid, L-theanine, malic acid and curcumin, or a combination thereof.
68. The composition of any one of claims 53 to 67, wherein the composition is stable at room temperature for at least one week with <30% decrease, <20% decrease or less than 10% decrease in amount of the one or more cannabinoids.
69. A method of reducing the incidence and / or severity of a disease, disorder or condition, the method comprising administering a composition of any one of claims 53 to 68 to a subject in need thereof.
70. The method of claim 69, wherein the composition reduces the incidence and / or severity of a disease, disorder or condition in the subject by improving overall health of the subject.71 . The method of claim 70, wherein the improving overall health of the subject is by supporting the subject’s body’s own ability to reduce pain and / or inflammation.
72. A method of improving resistance to a disease, disorder or condition and / or improving immune response, the method comprising administering a composition of any one of claims 53 to 68 to a subject in need thereof.
73. The method of claim 72, wherein the composition improves resistance to a disease, disorder or condition and / or improves immune response by maintaining or promoting health, including nutrient structure-function, to support the subject’s body’s own ability to resist the disease, disorder or condition and / or improve immune response..
74. The method of any one of claims claim 69 to 73, wherein the disease, disorder or condition is Alzheimer's disease; Parkinson's disease; essential tremor; amyotrophic lateral sclerosis (ALS); Huntington's disease; Friedreich's ataxia; multiple sclerosis; frontotemporal dementia; prion disease; Lewy body dementia; progressive supranuclear palsy; vascular dementia; normal pressure hydrocephalus; traumatic spinal cord injury; human immunodeficiency virus (HIV) dementia; alcohol induced neurotoxicity; Down's syndrome; movement disorders of the central and / or peripheral nervous system; motor neurone diseases (MND); spinal muscular atrophy; or any other related neurological or psychiatric neurodegenerative disease; brain damage; brain injury; brain dysfunction; dysgraphia; dysarthria; apraxia; agnosia; amnesia; dizziness; vertigo; coma; stroke; spinal cord damage; spinal cord injury; spinal corddisorders; central neuropathy; peripheral neuropathy; cranial nerve disorder; trigeminal neuralgia; tumors of the nervous system; infections of the brain or spinal cord; encephalitis; meningitis; prion disease; complex regional pain syndrome; an autonomic nervous system disorder; autonomic neuropathy; dysautonomia; postural orthostatic tachycardia syndrome (POTS); neurocardiogenic syncope (NCS); multiple system atrophy (MSA); hereditary sensory and autonomic neuropathy (HSAN); Holmes-Adie syndrome (HAS); a sleep disorder; narcolepsy; pain such as acute pain and chronic pain; migraine; cluster headache; tension headache; joint pain, back pain; lower back pain; neck pain; neuropathic pain; cancer pain; allodynia; osteoarthritic pain; inflammatory pain; a neuropsychiatric disorder; attention deficit hyperactivity disorder; autism; Tourette's Syndrome; obsessive compulsive disorder; an autism spectrum disorder; Rett syndrome; Fragile X syndrome; Angelman syndrome; hyperkinetic disorder; Tourette syndrome; dystonia; a cancer; brain cancer; glioma; breast cancer; liver cancer; lung cancer; pancreatic cancer; melanoma; ovarian cancer; gastric cancer; renal cancer; bladder cancer; addiction; nicotine addiction; smoking; alcohol addiction; drug addiction; Cannabis use disorder; a mental disorder; post-traumatic stress disorder; anxiety; early psychosis; schizophrenia; a cognitive disorder; stroke; cardiac ischemia; coronary artery disease; thromboembolism; myocardial infarction; ischemic related disease; a gastrointestinal disorder; inflammatory bowel disease; Crohn's disease; ulcerative colitis; nausea; vomiting; emesis; motion sickness; chemotherapy induced nausea; chemotherapy induced nausea vomiting; inflammation; arthritis; rheumatoid arthritis; osteoarthritis; diabetes; high blood pressure; poor insulin control; appetite suppression; anorexia; neonatal hypoxic-ischemic encephalopathy (NHIE); a degenerative skeletal muscle disease; or Duchenne muscular dystrophy (DMD).
75. The method of any one of claims 69 to 74, wherein the subject is human.
76. The method of claim 74 or claim 75, wherein the disease, disorder or condition is joint pain.
77. The method of claim 74 or claim 75, wherein the disease, disorder or condition is inflammatory pain.
78. The method of claim 74 or claim 75, wherein the disease, disorder or condition is osteoarthritic pain.
79. The method of any one of claims 76 to 78, wherein the intensity or duration of pain in the subject is reduced or the pain is eliminated.
80. The method of claim 79, wherein the pain intensity is reduced for at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 18 hours, or at least 24 hours post administration.
81. A method of preparing an emulsion comprising one or more cannabinoid compounds, the method comprising: a) heating an aqueous solution of casein protein and whey protein to form an aqueous solution comprising a casein protein and whey protein complex; b) mixing the one or more cannabinoid compounds with an oil to form a first mixture; c) dispersing the mixture formed in b) in the aqueous solution of a) to form a second mixture; and d) homogenizing the second mixture formed in c) to form the emulsion.
82. The method of claim 81 , wherein the pH of the aqueous solution of casein protein and whey protein complex is adjusted to about 6 to about 9, prior to the heating in a).
83. The method of claims 82, wherein the casein protein and whey protein complex is formed by heating the aqueous solution of casein and whey protein at about 70° C to about 100° C.
84. The method of claim 83, further comprising cooling the aqueous solution to below about 20° C after heating.
85. The method of claim 84, further comprising adjusting the pH of the aqueous solution of casein protein and whey protein complex to below about 4 after heating in a).
86. The method of any one of claims 81 to 85, wherein the homogenizing in d) is performed by a top homogenizer.
87. The method of claim 86, wherein the homogenizing in d) comprises using a microfluidizer at about 2,500 psi and about 40,000 psi pressure.
88. The method of any one of claims 81 to 87, wherein the one or more cannabinoid compounds are selected from cannabigerolic acid (CBGA), cannabigerolic acid monomethylether (CBGAM), cannabigerol (CBG), cannabigerol monomethylether (CBGM), cannabigerovarinic acid (CBGVA), cannabigerovarin (CBGV), cannabichromenicAcid (CBCA), cannabichromene (CBC), cannabichromevarinicacid (CBCVA), cannabichromevarin (CBCV), cannabidiolic acid (CBDA), cannabidiol (CBD), A6 cannabidiol (A6-CBD), cannabidiol monomethylether (CBDM), cannabidiol- C4 (CBD C4), cannabidivarinic acid (CBDVA), cannabidivarin (CBDV), cannabidiorcol (CBD C1), tetrahydrocannabinolic acid A (THCA-A), tetrahydrocannabinolic acid B (THCA-B), tetrahydrocannabinol (THC or A9-THC), A8-tetrahydrocannabinol (A8- THC), A10-tetrahydrocannabinol (A10-THC), tetrahydrocannabinolic acid C4 (THCA- C4), tetrahydrocannbinol C4 (THC C4), tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabivarin (THCV), A8-tetrahydrocannabivarin (A8-THCV), A9 tetrahydrocannabivarin (A9-THCV), tetrahydrocannabiorcolic acid (THCA-C1), tetrahydrocannabiorcol (THC-C1), delta 7 cis iso tetrahydrocannabivarin, A8 tetrahydrocannabinolic acid (A8-THCA), A9 tetrahydrocannabinolic acid (A9-THCA), cannabicyclolic acid (CBLA), cannabicyclol (CBL), cannabicyclovarin (CBLV), cannabielsoic acid A (CBEA-A), cannabielsoic acid B (CBEA-B), cannabielsoin (CBE), cannabinolic acid (CBNA), cannabinol (CBN), cannabinol methylether (CBNM), cannabinol-C4 (CBN-C4), cannabivarin (CBV), cannabino-C2 (CBN-C2), cannabiorcol (CBN-C1), cannabinodiol (CBND), cannabinodivarin (CBDV), cannabitriol (CBT), 11 hydroxy-A9-tetrahydrocannabinol (11 OH-THC), 11 nor 9-carboxy-A9- tetrahydrocannabinol ethoxy-cannabitriolvarin (CBTVE), 10 ethoxy-9-hydroxy-A6a- tetrahydrocannabinol, cannabitriolvarin (CBTV), 8,9 dihydroxy-A6a(10a)- tetrahydrocannabinol (8,9-Di-OH-CBT-C5), dehydrocannabifuran (DCBF), cannbifuran (CBF), cannabichromanon (CBCN), cannabicitran (CBT), 10 oxo- A6a(10a)-tetrahydrocannabinol (OTHC), A9-cis-tetrahydrocannabinol (cis-THC), cannabiripsol (CBR), 3,4,5,6-tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n- propyl-2,6-methano-2H-1-benzoxocin-5-methanol (OH-iso-HHCV), and trihydroxy- delta-9-tetrahydrocannabinol (triOH-THC), or any combination thereof.
89. The method of claim 88, wherein the one or more cannabinoid compounds are comprised in a distillate, an isolate, cannabis oil, cannabis extract or a combination thereof.
90. The method of claim 89, wherein the one or more cannabinoid compounds are comprised in a distillate.91 . The method of claim 89, wherein the one or more cannabinoid compounds are comprised in an isolate.
92. The method of claim 89, wherein the one or more cannabinoid compounds are comprised in a cannabis oil.
93. The method of claim 89, wherein the one or more cannabinoid compounds are comprised in a cannabis extract.
94. The method of any claims 88 to 93, wherein the one or more cannabinoid compounds is or comprises CBG, or a salt, isomer, enantiomer, or optically active derivative thereof.
95. The method of claim 94, wherein the one or more cannabinoid compounds is or is comprised in a CBG distillate.
96. The method of claim 94, wherein the one or more cannabinoid compounds is or is comprised in a CBG isolate.
97. The method of any claims 88 to 93, wherein the one or more cannabinoid compounds is or comprises CBD, or a salt, isomer, enantiomer, or optically active derivative thereof.
98. The method of claim 97, wherein the one or more cannabinoid compounds is or is comprised in a CBD distillate.
99. The method of claim 97, wherein the one or more cannabinoid compounds is or is comprised in a CBD isolate.
100. The method of any claims 88 to 93, wherein the one or more cannabinoid compounds is or comprises THC, or a salt, isomer, enantiomer, or optically active derivative thereof.101 . The method of claim 100, wherein the one or more cannabinoid compounds is or is comprised in a THC distillate.
102. The method of claim 100, wherein the one or more cannabinoid compounds is or is comprised in a THC isolate.
103. The method of any one of claims 88 to 102, wherein the one or more cannabinoid compounds are present in the emulsion in an amount of about 0.25 wt% to about 13 wt% of the emulsion.
104. The method of any one of claims 88 to 103, wherein the emulsion further comprises one or more terpenes, one or more terpenoids, one or more flavonoids, and any combinations thereof.
105. The method of claim 104, wherein the emulsion further comprises one or more terpenes and / or one or more terpenoids.
106. The method of claim 105, wherein the one or more terpenes and / or one or more terpenoids are present in the emulsion in an amount of about 0 to about 13 wt% of the emulsion.
107. The method of any one of claims 81 to 106, wherein the whey protein is selected from whey protein isolate, whey protein concentrate, a-lactalbumin and p-lacoglobulin.
108. The method of claim 107, wherein the whey protein is whey protein isolate.
109. The method of any one of claims 81 to 108, wherein the casein protein is selected from a-casein, K-casein, p-casein, b-casein, and their salts, such as sodium, potassium, calcium and ammonium, or mixtures thereof.
110. The method of claim 109, wherein the casein protein is sodium caseinate.
111. The method of claim 107 or 108, wherein the whey protein is present in the emulsion in an amount of about 0.25 wt% to about 5 wt% of the emulsion.
112. The method of claim 109 or 110, wherein the casein protein is present in the emulsion in an amount of about 0.25 wt% to about 5 wt% of the emulsion.
113. The method of any one of claims 105 or 106, wherein the weight ratio of casein protein to whey protein is about 10:1 to about 1 :10.
114. The method of any one of claims 107 to 113, wherein the whey protein is present in the emulsion in an amount of about 1.3 wt% and the casein protein is present in the emulsion in an amount of about 1 .3 wt%.
115. The method of any one of claims 81 to 114, wherein the oil is omega-3 oil.
116. The method of claim 115, wherein the omega-3 oil is selected from oils obtained from fish such as salmon, tuna, herring, mackerel, anchovies, sardines, pollock, cod,catfish, flounder, grouper, halibut, mahi mahi, orange roughy, red snapper, shark, swordfish, tilefish, plankton, algae, krill and / or green-lipped mussel, and / or plant oils such as canola oil, borage oil, evening primrose oil, safflower oil, sunflower oil, flaxseed oil, wheat germ oil, algal oil, and / or grapeseed oil, and / or oils obtained from chia seeds, kiwifruit seeds, peri Ila seeds, lingonberry seeds, camelina seeds, purslane seeds, black raspberry seeds, hemp seeds, butternut, walnuts, pecan nuts, and / or hazel nuts.
117. The method of claim 116, wherein the oil is sunflower oil.
118. The method of claim 116, wherein the oil is algal oil.
119. The method of any one of claims 115 to 118, wherein the oil is present in the emulsion in an amount of about 8 wt% to about 30 wt% of the emulsion.
120. The method of any one of claims 115 to 118, wherein the weight ratio of oil to one or more cannabinoid compounds is about 100:1 to about 1 :1 .
121. The method of any one of claims 81 to 120, wherein the emulsion further comprises one or more pH adjusting agents selected from sodium acetate, phosphoric acid, acetic acid, lactic acid, fumaric acid, adipic acid, malic acid, tartaric acid, citric acid, hydrochloric acid, sulfuric acid, potassium hydroxide, salts thereof, and combinations thereof.
122. The method of claim 121 , wherein the one or more pH adjusting agents comprise citric acid and potassium hydroxide.
123. The method of claim 121 or 122, wherein the one or more pH adjusting agents are present in the emulsion in an amount of about 0.1 wt% to about 5 wt% of the emulsion.
124. The method of any one of claims 81 to 123, wherein the emulsion further comprises one or more anti-foaming agents.
125. The method of claims 124, wherein the one or more anti-foaming agents are present in the emulsion in an amount of about 0.005 wt% to about 0.1 wt % of the emulsion.
126. The method of any one of claims 81 to 125, wherein the emulsion has an average particle size of below about 1000 nm.
127. The method of any one of claims 81 to 126, wherein the emulsion is stable at room temperature for at least two weeks or for at least three weeks.
128. The method of any one of claims 81 to 127, wherein the emulsion has zeta potential of above about 30 mV.
129. The method of any one of claims 81 to 128, further comprises heat treating or sterilization.
130. A method of making a dry powder formulation of claim 50 comprising drying the emulsion of any one of claims 1 to 48 to form a powder.
131. A method of making a liquid composition of claims 53 to 68 comprising diluting the emulsion of any one of claims 1 to 48 or mixing the powder formulation of claim 50 with a suitable liquid to form the composition.
132. The method of claim 131 , wherein the liquid used for dilution is selected from liquid selected from water, oil, alcohol, non-alcoholic drink, soft drink, fruit juice, vegetable juice, tea, coffee, milk and punch.