WO2023067509A1 - Compositions pour complémenter des produits de kombucha avec des agents thérapeutiques et leurs procédés de fabrication et d'utilisation - Google Patents

Compositions pour complémenter des produits de kombucha avec des agents thérapeutiques et leurs procédés de fabrication et d'utilisation Download PDF

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Publication number
WO2023067509A1
WO2023067509A1 PCT/IB2022/060018 IB2022060018W WO2023067509A1 WO 2023067509 A1 WO2023067509 A1 WO 2023067509A1 IB 2022060018 W IB2022060018 W IB 2022060018W WO 2023067509 A1 WO2023067509 A1 WO 2023067509A1
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Prior art keywords
several embodiments
lipid
extract
composition
beverage
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PCT/IB2022/060018
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English (en)
Inventor
Brian R. SLOAT
Michael A. Sandoval
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Disruption Labs, Inc.
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Publication of WO2023067509A1 publication Critical patent/WO2023067509A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23F—COFFEE; TEA; THEIR SUBSTITUTES; MANUFACTURE, PREPARATION, OR INFUSION THEREOF
    • A23F3/00—Tea; Tea substitutes; Preparations thereof
    • A23F3/16—Tea extraction; Tea extracts; Treating tea extract; Making instant tea
    • A23F3/163—Liquid or semi-liquid tea extract preparations, e.g. gels, liquid extracts in solid capsules
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/38—Other non-alcoholic beverages
    • A23L2/382—Other non-alcoholic beverages fermented
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/062—Ascomycota
    • A61K36/064—Saccharomycetales, e.g. baker's yeast
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
    • A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A61K9/1277—Processes for preparing; Proliposomes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10—Preparation or pretreatment of starting material
    • A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment

Definitions

  • This disclosure relates generally to lipid, micro- and/or nanoparticle-based compositions (e.g., liposomal, solid lipid particles, oil-in-water emulsions, etc.) and their use in methods for the delivery of hydrophobic and/or hydrophilic therapeutic agents (e.g., vitamins, nutrients, plant extracts, nutraceuticals, pharmaceuticals, or other beneficial agents for delivery) to subjects.
  • hydrophobic and/or hydrophilic therapeutic agents e.g., vitamins, nutrients, plant extracts, nutraceuticals, pharmaceuticals, or other beneficial agents for delivery
  • the particle compositions are suspended in solution (e.g., kombucha broth).
  • the lipid compositions comprise individual components of and/or combinations of hemp extracts, cannabinoids, a mushroom extract, a kratom extract, a kava extract, and/or a kana extract as a therapeutic agent or therapeutic ingredient.
  • the compositions are stable (e.g., at room temperature) for prolonged periods of time.
  • Kombucha is a fermented, lightly effervescent, sweetened black or green tea drink commonly consumed for its purported health benefits.
  • the culture is often called tea mushroom, tea fungus, or Manchurian mushroom.
  • the beverage is called kombucha tea to distinguish it from the culture of bacteria and yeast. Juice, spices, fruit or other flavorings may be added.
  • Kombucha is produced by fermenting sugared tea using a symbiotic culture of bacteria and yeast (SCOBY) commonly called a “mother” or “mushroom”.
  • the yeast generally includes Saccharomyces cerevisiae or other species.
  • the bacteria often includes Gluconacetobacter xylinus.
  • Gluconacetobacter xylinus can oxidize yeast-produced alcohols to acetic acid (and other acids).
  • SCOBY is often referred to as a symbiotic growth of acetic acid bacteria and osmophilic yeast species in a zoogleal mat biofilm.
  • the living bacteria in kombucha are probiotic.
  • a particle composition and/or a lipid-based particle composition for the delivery of an active agent (e.g., a therapeutic agent) to an fermented and/or alcoholic beverage, such as kombucha (or similar fermented caffeinated beverages).
  • an active agent e.g., a therapeutic agent
  • the particle is a lipid particle.
  • the particle is a nanoscale particle.
  • the particle is a microscale particle.
  • the particle is liposomal (e.g., is a liposome).
  • the particle comprises, consists of, or consists essentially of one or more of a phospholipid component, a non-phospholipid lipid component (e.g., a medium and/or long chain triglyceride component), a sterol component, and/or water.
  • the particle comprises, consists of, or consists essentially of one or more of a phospholipid component, a non-phospholipid lipid component, a sterol component, water, and/or an therapeutic ingredient (e.g., a therapeutic agent or combination of therapeutic agents).
  • the particle is liposomal (e.g., is a liposome).
  • the particle comprises, consists of, or consists essentially of one or more of a phospholipid component, a non-phospholipid lipid component (e.g., a medium and/or long chain triglyceride component), and/or a sterol component.
  • the particle comprises, consists of, or consists essentially of one or more of a phospholipid component, a non-phospholipid lipid component, a sterol component, and/or an therapeutic ingredient.
  • the particle comprises an active ingredient (e.g., a therapeutic agent) and/or a combination of active ingredients (e.g., therapeutic agents).
  • the particle comprises the therapeutic ingredient comprises a fungus extract, a kratom extract, a Kanna extract, a kava extract, or combinations thereof.
  • the particle comprises a therapeutic ingredient at a weight percent in the composition ranging from 0.01% to 20%.
  • the particle comprises the therapeutic ingredient comprises a fungus extract, a kratom extract, a Kanna extract, a kava extract, a hemp extract, a cannabis extract, or combinations thereof.
  • the particle comprises a phosphatidylcholine at a weight percent in the composition ranging from 1% to 25%.
  • the particle comprises a sterol at a weight percent in the composition ranging from 0.1% to 10%.
  • the particle comprises a lipid component at a weight percent in the composition ranging from 0% to 24% or where the particle does not comprise the lipid component. In several embodiments, the particle comprises water at a weight percent in the composition ranging from 21% to about 95%.
  • the particle comprises water at a weight percent in the composition ranging from 0% (anhydrous) to about 20%, a therapeutic ingredient at a weight percent of the lipid-based particles from 0.01% to 20%, a phosphatidylcholine at a weight percent in the lipid-based particles from 25% to 60%, a sterol at a weight percent in the lipid- based particles from 0.5% to 10%, and a lipid component at a weight percent in the lipid- based particles from 0% to 50% or where the particle does not comprise the lipid component.
  • the particle comprises, consists of, or consists essentially of nanoparticles having an average size ranging from about 20 nm to about 500 nm.
  • the average size of the nanoparticles changes less than or equal to 20%.
  • the composition comprises liposomes and/or an oil-in- water nano-emulsion and/or a solid lipid nanoparticle.
  • an appreciable amount of the nanoparticle composition does not settle and/or separate from solution upon standing for a period of at least about one month.
  • the composition is configured such that when concentrated to dryness to afford a powder formulation of nanoparticles, the nanoparticle powder can be reconstituted to provide the nanoparticle composition.
  • the average size of the nanoparticles changes by less than about 20%.
  • the polydispersity of the nanoparticles in the composition is less than or equal to 0.25.
  • the polydispersity of the nanoparticles changes by less than or equal to 100%. In several embodiments, upon 90 days of storage at 25°C and 60% relative humidity, the polydispersity of the nanoparticles changes by less than or equal to 0.1. In several embodiments, upon 3, 6, 9, 12, 15, 30, 45, 60, 90 or more days of storage at 25°C and 60% relative humidity, the D90 of the nanoparticles changes less than or equal to 20%. In several embodiments, when exposed to simulated gastric fluid at a pH of 1.6 for a period of at least 1 hour, the average size of the nanoparticles changes less than or equal to 20%.
  • the composition when exposed to simulated intestinal fluid at a pH of 6.5 for a period of at least 1 hour, the average size of the nanoparticles changes less than or equal to 20%.
  • the composition comprises a particle.
  • the particle comprises a therapeutic ingredient at a weight percent in the composition ranging from 0.01% to 20%.
  • the therapeutic ingredient comprises a fungus extract, a kratom extract, a Kanna extract, a kava extract, or combinations thereof.
  • the particle comprises a phosphatidylcholine at a weight percent in the composition ranging from 25% to 60%.
  • the particle comprises a sterol at a weight percent in the composition ranging from 0.5% to 10%.
  • the particle comprises a lipid component (e.g., a lipid component that is not a phospholipid) at a weight percent in the composition ranging from 0% to 50%.
  • the lipid-based particle is anhydrous, or contains water at up to 21% by weight of the composition.
  • the lipid-based particle composition is provided as a dry powder.
  • the powder is configured to be reconstituted in water to provide an aqueous solution.
  • nanoparticles within the aqueous solution have an average size ranging from about 20 nm to about 500 nm.
  • nanoparticles within the aqueous solution upon reconstitution, have an average size ranging from about 75 nm to about 200 nm.
  • the average size of the nanoparticles when reconstituted and exposed to simulated gastric fluid at a pH of 1.6 for a period of at least 1 hour, the average size of the nanoparticles changes less than or equal to 10%.
  • the average size of the nanoparticles when reconstituted and exposed to simulated intestinal fluid at a pH of 6.5 for a period of at least 1 hour, changes less than or equal to 10%.
  • the lipid component is a short chain triglyceride, a medium chain triglyceride, a long chain triglyceride, or a combination of any of the foregoing.
  • the average size of the nanoparticles changes less than 2%.
  • the sterilization conditions are selected from the group consisting of ozonation, UV treatment, and/or pasteurization.
  • the composition further comprises a preservative.
  • the preservative comprises one or more of malic acid, citric acid, potassium sorbate, sodium benzoate, and Vitamin E.
  • the sterol is cholesterol.
  • the composition further comprises a flavoring agent.
  • the therapeutic ingredient comprises a full spectrum extract of a psilocybin mushroom, a broad spectrum extract of a psilocybin mushroom, a distillate of a psilocybin mushroom, or an isolate of a psilocybin mushroom.
  • the therapeutic ingredient comprises a full spectrum extract of kratom, a broad spectrum extract of kratom, a distillate of kratom, or an isolate of kratom.
  • the therapeutic ingredient comprises a full spectrum extract of Kanna, a broad spectrum extract of Kanna, a distillate of Kanna, or an isolate of Kanna.
  • the therapeutic ingredient comprises a full spectrum extract of kava, a broad spectrum extract of kava, a distillate of kava, or an isolate of kava. In several embodiments, the therapeutic ingredient further comprises a full spectrum extract of hemp, a broad spectrum extract of hemp, a distillate of hemp, or an isolate of hemp. In several embodiments, the therapeutic ingredient further comprises a full spectrum extract of cannabis, a broad spectrum extract of cannabis, a distillate of cannabis, or an isolate of cannabis.
  • the therapeutic ingredient consists of or consists essentially of a full spectrum extract of a psilocybin mushroom, a broad spectrum extract of a psilocybin mushroom, a distillate of a psilocybin mushroom, or an isolate of a psilocybin mushroom.
  • the therapeutic ingredient consists of or consists essentially of a full spectrum extract of kratom, a broad spectrum extract of kratom, a distillate of kratom, or an isolate of kratom.
  • the therapeutic ingredient consists of or consists essentially of a full spectrum extract of kava, a broad spectrum extract of kava, a distillate of kava, or an isolate of kava. In several embodiments, the therapeutic ingredient consists of or consists essentially of a full spectrum extract of Kanna, a broad spectrum extract of Kanna, a distillate of Kanna, or an isolate of Kanna.
  • the therapeutic ingredient comprises, consists of, or consists essentially of an alkaloid (e.g., from a mushroom, kratom, kava, kanna, or combinations thereof), psilocin (3-[2 (dimethylamino)ethyl]-4-indolol), psilocybin ([3-(2- dimethylaminoethyl)-l//-indol-4-yl] dihydrogen phosphate), baeocystin, norbaeocystin, bufotenin, aeruginascin, mitaphylline, 7-OH-mitragynine, paynantheine, speciogynine, mitragynine, mitrajavine, ajmalicine, raubasine, akuammigine, ciliaphylline, corynantheidine, corynoxeine, corynoxine A and/or B, epic
  • the therapeutic ingredient further comprises one or more additional therapeutic agents.
  • the lipid-based particle composition and/or lipid-based particle is contained in an aqueous liquid, such as a beverage.
  • the beverage is an alcoholic beverage and/or a fermented beverage.
  • the lipid-based particle composition can be diluted by the aqueous liquid to have a final concentration of the lipid- based particle composition in the aqueous liquid of less than, more than, equal to, or between 50, 40, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, 0.02, 0.01 percent by weight or by volume of the aqueous liquid and lipid-based particle composition combination.
  • Some embodiments pertain to a method of treating a patient in need of treatment comprising administering an effective amount of the lipid-based particle composition as disclosed above and/or anywhere else herein or the fortified biomass as disclosed above and/or anywhere else herein.
  • the method comprises providing phosphatidylcholine. In several embodiments, the method comprises providing a lipid component. In several embodiments, the method comprises mixing the medium chain triglyceride and phosphatidylcholine to provide a solution. In several embodiments, the method comprises passing the solution through a microfluidizer to provide a lipid-based particle composition. In several embodiments, the method comprises mixing a therapeutic ingredient with the lipid-based particle composition. In several embodiments, the method further comprises adding one or more sterols to the solution. In several embodiments, the method further comprises adding water to the solution.
  • the active ingredient or combination of active ingredients comprise a mixture of therapeutics isolated from a plant source (e.g., a full spectrum mixture).
  • the active ingredient or combination of active ingredients comprise one or more cannabinoids.
  • the one or more cannabinoids include one or more phytocannabinoids (e.g., combinations of phytocannabinoids).
  • the one or more phytocannabinoids comprise CBD.
  • the lipid constituents of the particle allow the particle to solubilize CBD (or other phytocannabinoids or cannabinoids) of high purity.
  • the CBD in the particle is of sufficient purity to provide a crystalline and/or solid (e.g., an amorphous or crystalline powder).
  • the CBD not an oil.
  • the active ingredient or combination of active ingredients comprise one or more non-cannabinoid therapeutic agents.
  • the therapeutic agent comprises, consists of, or consists essentially of a synthetic therapeutic agent, non- synthetic therapeutic agent, and/or combinations thereof.
  • the therapeutic agent or combination of therapeutic agents e.g., one or more extracts or active agents from or found in hemp, cannabis, fungus, kratom, Kanna, or kava
  • an aqueous composition at a concentration of greater than or equal to about: 200 mg/ml, 150 mg/ml, 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, or ranges including and/or spanning the aforementioned values.
  • the one or more therapeutic agent(s) are present in the composition at a dry wt.% of equal to or at least about: 0.01%, 0.05%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 70%, or ranges including and/or spanning the aforementioned values.
  • the one or more therapeutic agent(s) are present in the composition at a wet Wt.% of equal to or at least about: 0.01%, 0.05%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, or ranges including and/or spanning the aforementioned values.
  • the phytocannabinoid of a lipid-based particle composition as disclosed herein is a single phytocannabinoid (e.g., CBD).
  • the phytocannabinoid e.g., CBD
  • the phytocannabinoid has a purity by weight % of equal to or greater than about: 70%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, 100%, or ranges including and/or spanning the aforementioned values.
  • the phytocannabinoid (e.g., CBD) is present in the lipid-based particle composition at dry weight % of equal to or greater than about: 5%, 8%, 10%, 15%, 20%, or ranges including and/or spanning the aforementioned values.
  • the phytocannabinoid is free of or essentially free of THC.
  • the phytocannabinoid e.g., CBD
  • THC is present below the limit of quantitation (LOQ) (e.g., when analyzed by high pressure liquid chromatography (HPLC) with standard detectors, such as UV/Vis, photodiode array, refractive index, fluorescence, light scattering, conductivity, and the like).
  • LOQ limit of quantitation
  • the phospholipid component comprises, consists of, or consists essentially of one or more of phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidylinositol phosphate, phosphatidylinositol bisphosphate, and phosphatidylinositol trisphosphate.
  • the phospholipid component comprises phosphatidylcholine.
  • the phospholipid component is a single phospholipid.
  • the phospholipid component is phosphatidylcholine.
  • the phosphatidylcholine is highly pure. In several embodiments, the phosphatidylcholine has a purity by weight % of equal to or greater than about: 97%, 98%, 99%, 100%, or ranges including and/or spanning the aforementioned values.
  • the phosphatidylcholine is present in the lipid-based particle composition at dry weight % of equal to or greater than about: 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, or ranges including and/or spanning the aforementioned values.
  • the phospholipid component comprises, consists of, or consists essentially of a synthetic phospholipid, non-synthetic phospholipid, and/or combinations thereof.
  • the lipid component (e.g., the lipid component that is not a phospholipid) comprises, consists of, or consists essentially of a triglyceride. In several embodiments, where present, the lipid component (e.g., the lipid component that is not a phospholipid) comprises, consists of, or consists essentially of a fatty acid (or fatty acids). In several embodiments, the lipid component comprises a medium chain triglyceride (MCT).
  • MCT medium chain triglyceride
  • the medium chain triglyceride comprises a fatty acid selected from one or more of caproic acid, octanoic acid, capric acid, caprylic acid, and/or lauric acid (e.g., is formed from).
  • the medium chain triglyceride comprises a fatty acid tail 6-12 carbons in length (e.g., 6, 7, 8, 9, 10, 11, or 12).
  • the lipid component comprises a long chain triglyceride.
  • the long chain triglyceride comprises a fatty acid tail greater than 12 carbons in length (e.g., greater than or equal to 13, 14, 15, 16, 17, 18, 19, or 20 carbons in length, or ranges including and/or spanning the aforementioned values).
  • the lipid component comprises a short chain triglyceride (SCT).
  • the short chain triglyceride comprises a fatty acid tail less than 6 carbons in length (e.g., less than or equal to 5, 4, 3, 2, 1 carbons in length, or ranges including and/or spanning the aforementioned values).
  • the lipid component is a single lipid.
  • the lipid component is MCT.
  • the MCT is highly pure.
  • the lipid component e.g., SCT, MCT, LCT, or combination thereof
  • the purity by weight % of equal to or greater than about: 90%, 95%, 97%, 98%, 99%, 100%, or ranges including and/or spanning the aforementioned values.
  • the lipid component (e.g., MCT, SCT, LCT, or combination thereof) is present in the lipid-based particle composition at dry weight % of equal to or greater than about: 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or ranges including and/or spanning the aforementioned values.
  • the non-phospholipid lipid component comprises, consists of, or consists essentially of a synthetic non-phospholipid lipid, non-synthetic non-phospholipid lipid, and/or combinations thereof.
  • the sterol component comprises, consists of, or consists essentially of cholesterol. In several embodiments, where present, the sterol component comprises, consists of, or consists essentially of a single sterol. In several embodiments, the sterol component is cholesterol. In several embodiments, multiple sterols are used. In several embodiments, the cholesterol (or other sterol) is highly pure. In several embodiments, the cholesterol (or other sterol) has a purity by weight % of equal to or greater than about: 97%, 98%, 99%, 100%, or ranges including and/or spanning the aforementioned values.
  • the cholesterol (or other sterol) is present in the lipid-based particle composition at dry weight % of equal to or greater than about: 0.1, 0.5, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 9%, 10%, or ranges including and/or spanning the aforementioned values.
  • the sterol component comprises, consists of, or consists essentially of a synthetic sterol, a non-synthetic sterol, and/or combinations thereof.
  • the lipid-based particle composition is aqueous while in other embodiments the composition may be provided as a dry or substantially dry solid (e.g., having a water content in weight % of less than or equal to 21%, 20%, 15%, 10%, 5%, 2%, 1%, 0.5%, or ranges including and/or spanning the aforementioned values).
  • water may be present at a wet weight percent of equal to or greater than about: 22%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 77%, 80%, 85%, or ranges including and/or spanning the aforementioned values.
  • the therapeutic ingredient such as phytocannabinoid (e.g., CBD) is present in the composition at wet weight % of equal to or greater than about: 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 5%, 8%, 10%, 15%, 20%, or ranges including and/or spanning the aforementioned values.
  • the phosphatidylcholine is present in the aqueous composition at wet weight % of equal to or greater than about: 1%, 5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values.
  • the MCT is present in the aqueous composition at wet weight % of equal to or greater than about: 0%, 1%, 5%, 10%, 15%, 20%, 24%, or ranges including and/or spanning the aforementioned values.
  • the cholesterol is present in the aqueous composition at wet weight % of equal to or greater than about: 0.1%, 0.5%, 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0% or ranges including and/or spanning the aforementioned values.
  • the particle comprises CBD, phosphatidylcholine, cholesterol, a lipid component other than a phospholipid (e.g., one or more of a medium chain triglyceride, a long chain triglyceride, and/or hemp oil), and/or water.
  • the CBD is present in an amount of less than or equal to about 25 mg/ml.
  • the phosphatidylcholine is present in an amount of less than or equal to about 100 mg/ml.
  • the cholesterol is present in an amount of less than or equal to about 25 mg/ml.
  • the medium chain triglyceride is present in an amount of less than or equal to about 100 mg/ml.
  • the lipid-based particle composition further comprises a preservative.
  • the preservative comprises one or more of malic acid, citric acid, potassium sorbate, sodium benzoate, and Vitamin E.
  • malic acid is present in an amount of less than or equal to about 0.85 mg/ml.
  • citric acid is present in an amount of less than or equal to about 0.85 mg/ml.
  • potassium sorbate is present in an amount of less than or equal to about 1 mg/ml.
  • sodium benzoate is present in an amount of less than or equal to about 1 mg/ml.
  • the composition further comprises a flavoring agent.
  • lipid-based particle composition comprising: a nanoparticle comprising: cannabidiol (CBD) that is of sufficient purity that it exists in a solid and/or powdered state prior to formulation in the nanoparticle composition at a weight percent in the composition ranging from 1% to 10%; a phosphatidylcholine at a weight percent in the composition ranging from 2.5% to 15%; a sterol at a weight percent in the composition ranging from 0.5% to 5%; and a medium chain triglyceride at a weight percent in the composition ranging from 2.5% to 15%.
  • the composition comprises water at a weight percent in the composition ranging from 60% to about 80%.
  • the nanoparticles have an average size ranging from about 75 nm to about 175 nm. In several embodiments, upon storage for a period of one month, the average size of the nanoparticles changes by less than about 20%.
  • the lipid-based particle composition is in the form of liposomes and/or an oil-in-water nano-emulsion.
  • an appreciable amount of the nanoparticle composition does not settle and/or separate from the water upon standing for a period of at least about 12 hours.
  • the composition is configured such that when concentrated to dryness to afford a powder formulation of nanoparticles, the nanoparticle powder can be reconstituted to provide the nanoparticle composition.
  • the composition has a Tmax for CBD of less than 4.5 hours.
  • the average size of the nanoparticles changes by less than about 20%.
  • the poly dispersity of the nanoparticles in the composition is less than or equal to 0.15. In several embodiments, upon 90 days of storage at 25°C and 60% relative humidity, the polydispersity of the nanoparticles changes by less than or equal to 10%. In several embodiments, upon 90 days of storage at 25°C and 60% relative humidity, the polydispersity of the nanoparticles changes by less than or equal to 0.1. In several embodiments, the composition has a shelf life of greater than 18 months at 25°C and 60% relative humidity. In several embodiments, upon 90 days of storage at 25°C and 60% relative humidity, the D90 of the nanoparticles changes less than or equal to 10%. In several embodiments, the composition has a concentration max (Cmax) of 80 ng/ml after an oral dose of 15 mg/kg.
  • lipid-based particle composition comprising a particle comprising cannabidiol (CBD) that is of sufficient purity that it exists in a solid and/or powdered state prior to formulation in the nanoparticle composition at a weight percent in the composition ranging from 5% to 15%, a phosphatidylcholine at a weight percent in the composition ranging from 35% to 60%, a sterol at a weight percent in the composition ranging from 2.5% to 10%, and a medium chain triglyceride at a weight percent in the composition ranging from 35% to 50%.
  • the composition further comprising a preservative.
  • the preservative comprises one or more of malic acid, citric acid, potassium sorbate, sodium benzoate, and Vitamin E.
  • the sterol is cholesterol.
  • the composition further comprises a flavoring agent.
  • the composition has a Cmax of 80 ng/ml after an oral dose of 15 mg/kg.
  • the lipid-based particle composition is provided as a dry powder.
  • the powder is configured to be reconstituted in water to provide an aqueous solution.
  • nanoparticles within the aqueous solution have an average size ranging from about 75 nm to about 175 nm.
  • the composition further comprising a preservative.
  • the preservative comprises one or more of malic acid, citric acid, potassium sorbate, sodium benzoate, and Vitamin E.
  • the sterol is cholesterol.
  • the composition further comprises a flavoring agent.
  • the lipid-based particle composition is in the form and/or comprises one or more of liposomes, an oil-in-water nanoemulsion (and/or microparticle emulsion), and/or solid lipid particles.
  • an appreciable amount of the particles in the composition do not settle and/or do not separate (e.g., upon visual inspection) from the water upon standing for a period of at least about 12 hours.
  • the particles when suspended in water, the particles remain substantially homogenously distributed in the water upon standing for a period of at least about 12 hours.
  • the nanoparticles have an average size ranging from about 10 nm to about 500 nm.
  • the composition comprises nanoparticles having an average size of less than or equal to about: 10 nm, 50 nm, 100 nm, 250 nm, 500 nm, 1000 nm, or ranges including and/or spanning the aforementioned values.
  • the composition comprises microparticles having an average size of less than or equal to about: 1000 nm, 1.5 pm, 2 pm, 3 pm, 5 pm, 10 pm or ranges including and/or spanning the aforementioned values.
  • the dried powder composition comprises microparticles that form nanoparticles (as disclosed herein) when reconstituted.
  • these dried powder compositions comprise particles having an average size of less than or equal to about: 250 nm, 500 nm, 1000 nm, 1.5 pm, 2 pm, 3 pm, 5 pm, 10 pm, 50 pm, or ranges including and/or spanning the aforementioned values.
  • the average size of the nanoparticles (or microparticles) increases by less than about 10%.
  • the lipid-based particle composition is configured such that when concentrated to dryness to afford dry particles (e.g., from any one of the oil-in- water emulsion (e.g., a nanoemulsion or microemulsion), liposome solution, and/or solid lipid particle) as a powder, the dry nanoparticles can be reconstituted to provide a reconstituted particle based solution (e.g., the nanoparticle composition).
  • the average size of the nanoparticles increases or decreases by less than about 15% and/or by less than about 100%.
  • excipients may be added to the liposomes, oil-in-water nano-emulsions (and/or microparticle emulsions), and/or a solid lipid particle.
  • the excipient comprises trehalose.
  • lipid-based particle composition e.g., in the fermented caffeinated beverage.
  • one or more phytocannabinoids e.g., CBD
  • one or more lipophilic components of the composition to provide a solution.
  • one or more lipid components that are not phospholipids
  • one or more sterols are added.
  • one or more phospholipids are added.
  • one or more flavoring and/or preservatives are added.
  • water is added.
  • the lipophilic ingredients are combined and the hydrophilic ingredients are combined separately.
  • the lipophilic ingredients are then added to the hydrophilic ingredients.
  • the solution is passed through a microfluidizer and/or a high sheer homogenizer.
  • the process affords a particle composition.
  • a method of manufacturing the particle composition of a phytocannabinoid is disclosed.
  • the phytocannabinoid is added to solvent.
  • one or more phospholipids are added to the solvent.
  • one or more sterols are added to the solvent.
  • one or more lipids is added to the solvent.
  • the solvent is removed to provide a substantially solid product.
  • the product is mixed with water to provide an emulsion.
  • the emulsion is passed through a microfluidizer and/or a high sheer homogenizer.
  • the process affords a nanoparticle composition.
  • a method of treating a patient in need of treatment comprising administering an effective amount therapeutic agent provided as a lipid-based particle composition as disclosed herein to the patient.
  • Some embodiments pertain to a method of treating a patient in need of treatment comprising administering an effective amount of the composition to the patient.
  • the patient in need of treatment is a patient suffering from one or more of pain, anxiety & stress, seizures, malaise, inflammation, mood disorders, and insomnia.
  • the condition is treated by administering an effective amount of a composition as disclosed herein to the patient.
  • the Cmax is increased relative to CBD alone or comparator embodiments (e.g., CBD oil-based products) by equal to or at least about: 15%, 20%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values.
  • the Cmax is increased (relative to an oil-based product) by equal to or at least about: 10 ng/mL, 20 ng/mL, 30 ng/mL, 40 ng/mL, 50 ng/mL, 60 ng/mL, 70 ng/mL, 80 ng/mL, 90 ng/mL, or ranges including and/or spanning the aforementioned values.
  • the Tmax for CBD is decreased (relative to CBD alone or a CBD in oil mixture) by equal to or at least about: 15%, 20%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values.
  • the Tmax for CBD in a disclosed embodiment is decreased (relative to CBD alone or a CBD in oil mixture) by equal to or at least about: 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, or ranges including and/or spanning the aforementioned values.
  • the AUC for CBD using a disclosed embodiment is increased (relative to CBD alone or a CBD in oil mixture) by equal to or at least about: 100 ng/mL*hr, 200 ng/mL*hr, 300 ng/mL*hr, 400 ng/mL*hr, or ranges including and/or spanning the aforementioned values.
  • the AUC is improved (relative to CBD alone or a CBD in oil mixture) by equal to or at least about: 25%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values.
  • Figure 1 is a flow chart showing an embodiment of a method of preparing a lipid- based particle composition as disclosed herein.
  • Figure 2 is a flow chart showing another embodiment of a method for preparing a lipid-based particle composition as disclosed herein.
  • Figure 3 depicts the CBD concentration in an embodiment of the disclosed lipid- based particle compositions over time when stored at 25°C/60% relative humidity.
  • Figure 4 depicts the particle size of an embodiment of the disclosed lipid-based particle compositions over time when stored at 25°C/60% relative humidity.
  • Figure 5 depicts representative images of some embodiments of lipid nanoparticles as disclosed herein.
  • Figure 6 depicts resulting Z-Average Particle Size of some embodiments after 5 microfluidization passes for embodiments prepared using solvent-free methods.
  • Figure 7 depicts resulting D90 Particle Size of some embodiments after 5 microfluidization passes for embodiments prepared using solvent-free methods.
  • Figure 8 depicts resulting polydispersity of some embodiments after 5 microfluidization passes for embodiments prepared using solvent-free methods.
  • Figure 9A-D depict the pharmacokinetic profiles of certain embodiments of CBD lipid nanoparticle solutions, CBD lipid nanoparticle powders and CBD oil-based commercial comparators.
  • Figure 9A shows CBD plasma concentration data for an embodiment as disclosed herein, including for a lipid nanoparticle solution and a lipid nanoparticle powder.
  • Figure 9B provides a comparison of the lipid nanoparticle powder of Figure 9A compared to commercial comparators comprising CBD oil.
  • Figure 9C provides a comparison of the lipid nanoparticle solution of Figure 9A compared to commercial comparators comprising CBD oil.
  • Figure 9D provides an expanded view of the data in Figure 9C.
  • Figure 10 depicts the Tmax for of CBD lipid nanoparticle as disclosed herein compared to and CBD oil-based commercial comparators.
  • Figure 11 depicts Half-Lives (T1/2) of some embodiments of CBD lipid nanoparticle solutions, powders, and oil-based commercial comparators.
  • Figure 12 depicts Area Under The Curve (AUC) of some embodiments of CBD lipid nanoparticle solutions, powders, and oil-based commercial comparators.
  • Figure 13 shows data for the change in CBD lipid nanoparticle particle size in several embodiments over approximately 6 months at different solution pH.
  • Figure 14 shows data for the change in CBD concentration in certain embodiments of lipid nanoparticles after 7 months at different storage conditions.
  • Figure 15 shows data for various passes through a microfluidizer, including an initial particle size measurements after 1 pass through 10 passes.
  • Figure 16 shows data for different particles after various passes through a microfluidizer, including particles after 1 pass through 10 passes after storage for 6 months at 25°C with 60% relative humidity.
  • Figure 17A-C shows change in particle size distribution by operating pressure measured using Z average, D90 particle sizing, and polydispersity index, respectively.
  • Figure 18 shows short-term stability data for various embodiments of CBD lipid nanoparticles prepared with cholesterol alternative phytosterols.
  • Figures 19A and 19B show stability data for various embodiments of CBD lipid nanoparticles in simulated gastric and simulated intestinal fluids.
  • Figure 20 shows stability data for various embodiments of CBD lipid nanoparticles.
  • Figure 21 shows embodiments of the lipid-based particle suspension solution.
  • Figures 22A and 22B show CBD concentration in kombucha beverages over time with starting concentrations of 20 mcg/mL and 180 mcg/mL, respectively.
  • Figure 23 shows encapsulated CBD concentration in three flavors of GT’s brand kombucha fermented beverage over time.
  • Figure 24 shows encapsulated CBD concentration in three flavors of ORGANIC BREW DR’s brand kombucha fermented beverage over time.
  • Figure 25 shows encapsulated CBD concentration in the three flavors of HEALTH- ADE brand kombucha fermented beverage over time.
  • Figure 26 shows encapsulated vitamin D3 concentration in watermelon flavor HEALTH- ADE’s brand kombucha fermented beverage over time.
  • Figure 27 shows encapsulated vitamin D3 concentration in love flavor of ORGANIC BREW DR’s brand kombucha fermented beverage over time.
  • Figure 28 shows 6 months of vitamin D3 stability data in HEALTH-ADE kombucha watermelon flavor and a shelf-life prediction using MINITAB® Version 21.2.
  • the lipid-based particle compositions are nanoparticle compositions.
  • the nanoparticles comprise liposomes.
  • the lipid-based particle compositions comprise one or more therapeutic agents (e.g., single therapeutic agents or combinations thereof).
  • one or more therapeutic agents may be a cannabinoid, a phytocannabinoid, a non-cannabinoid therapeutic, and/or a combination of any of the foregoing.
  • the phytocannabinoid is cannabidiol (CBD).
  • CBD cannabidiol
  • the composition is comprised of high-quality, pure, and/or high-grade ingredients (e.g., highly pure) that yield a well-characterized, reproducible delivery system (e.g., comprising lipid-based particles).
  • the lipid-based particle compositions as disclosed herein have enhanced stability (e.g., are stable for long periods of time under various conditions).
  • the composition confers water solubility to hydrophobic therapeutic agents, to combinations of hydrophobic therapeutic agents, and/or to combinations of hydrophobic and hydrophilic therapeutic agents.
  • the composition imparts apparent solubility to a compound (or compounds) that is otherwise considered practically insoluble in water (e.g., >10 liters of water needed to dissolve 1 gram of CBD) and/or a compound (or compounds) practically water insoluble according to the biopharmaceutical classification system.
  • the lipid-based particle composition comprises a liposomal and/or nano-emulsion composition of a therapeutic agent.
  • the lipid- based particle composition is configured for oral ingestion.
  • the lipid- based particle composition is suspended in a broth (e.g. a liquid medium containing proteins and/or other nutrients for the culture of bacteria) providing a lipid-based particle suspension solution.
  • the lipid-based particle composition is suspended in a fermented beverage, such as a caffeinated fermented beverage (e.g., kombucha, etc.). In some embodiments, the lipid-based particle composition is suspended in a kombucha (which may or may not be decaffeinated). In several embodiments, the lipid-based particle suspension solution as disclosed herein has enhanced stability (e.g., are stable for long periods of time under various conditions).
  • lipid-based particle compositions e.g., cannabinoids, phytocannabinoids, fish oils, vitamin D and other lipid soluble vitamins.
  • hydrophilic therapeutic agents may also be provided in the disclosed lipid-based particle compositions (e.g., alone, in combination with other hydrophilic therapeutic agents, and/or in combination with hydrophobic therapeutic agents).
  • the lipid-based particle compositions disclosed herein may enhance the delivery of and/or slow or lessen the degradation of hydrophilic or hydrophobic therapeutic agents (or combinations thereof).
  • nanoparticles e.g., lipid-based nanoparticles
  • microparticles are also envisioned.
  • the term “effective amount,” as used herein, refers to that amount of a recited compound and/or composition that imparts a modulating effect, which, for example, can be a beneficial effect, to a subject afflicted with a disorder, disease or illness, including improvement in the condition of the subject (e.g., in one or more symptoms), delay or reduction in the progression of the condition, prevention or delay of the onset of the disorder, and/or change in clinical parameters, disease or illness, etc., as would be well known in the art.
  • an effective amount can refer to the amount of a composition, compound, or agent that improves a condition in a subject by at least 5%, e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100%.
  • an improvement in a condition can be a reduction in disease symptoms or manifestations (e.g., pain, anxiety & stress, seizures, malaise, inflammation, mood disorders, insomnia, etc.).
  • Actual dosage levels of active ingredients in an active composition of the presently disclosed subject matter can be varied so as to administer an amount of the active compound(s) that is effective to achieve the desired response for a particular subject and/or application.
  • the selected dosage level will depend upon a variety of factors including, but not limited to, the activity of the composition, composition, route of administration, combination with other drugs or treatments, severity of the condition being treated, and the physical condition and prior medical history of the subject being treated.
  • a minimal dose is administered, and dose is escalated in the absence of dose-limiting toxicity to a minimally effective amount. Determination and adjustment of an effective dose, as well as evaluation of when and how to make such adjustments, are contemplated herein.
  • Treat” or “treating” or “treatment” refers to any type of action that imparts a modulating effect, which, for example, can be a beneficial effect, to a subject afflicted with a disorder, disease or illness, including improvement in the condition of the subject (e.g., in one or more symptoms), delay or reduction in the progression of the condition, and/or change in clinical parameters, disease or illness, curing the illness, etc.
  • the “patient” or “subject” treated as disclosed herein is, in several embodiments, a human patient, although it is to be understood that the principles of the presently disclosed subject matter indicate that the presently disclosed subject matter is effective with respect to all vertebrate species, including mammals, which are intended to be included in the terms “subject” and “patient.” Suitable subjects are generally mammalian subjects. The subject matter described herein finds use in research as well as veterinary and medical applications.
  • mammal as used herein includes, but is not limited to, humans, non-human primates, cattle, sheep, goats, pigs, mini-pigs (a mini-pig is a small breed of swine weighing about 35 kg as an adult), horses, cats, dog, rabbits, rodents (e.g., rats or mice), monkeys, etc.
  • Human subjects include neonates, infants, children, juveniles, adults and geriatric subjects.
  • the subject can be a subject “in need of’ the methods disclosed herein can be a subject that is experiencing a disease state and/or is anticipated to experience a disease state, and the methods and compositions of the invention are used for therapeutic and/or prophylactic treatment.
  • the term “weight percent” when referring to a component, is the weight of the component divided by the weight of the composition that includes the component, multiplied by 100%. For example, the weight percent of component A when 5 grams of component A is added to 95 grams of component B is 5% (e.g., 5 g A / (5 g A + 95 g B) x 100%).
  • the “dry weight %” e.g., “dry wt %”, “dry weight percent”, etc.” of an ingredient is the weight percent of that ingredient in the composition where the weight of water has not been included in the calculation of the weight percent of that ingredient.
  • a dry weight % can be calculated for a composition that does not include water or for a composition that includes water.
  • the “wet weight %” e.g., “wet wt %”, “wet weight percent”, etc.
  • the dry weight percent of component A when 5 grams of component A is added to 95 grams of component B and 100 grams of water is 5% (e.g., 5 g A / (5 g A + 95 g B) x 100%).
  • the wet weight percent of component A when 5 grams of component A is added to 95 grams of component B and 100 grams of water is 2.5% (e.g., 5 g A / (5 g A + 95 g B + 100 g water) x 100%).
  • A may be at 5 wt % and B may be at 5 wt %, totaling 10 wt %.
  • the terms “or ranges including and/or spanning the aforementioned values” is meant to include any range that includes or spans the aforementioned values.
  • the wt % of an ingredient is expressed as “1%, 5%, 10%, 20%, or ranges including and/or spanning the aforementioned values,” this includes wt % ranges for the ingredient spanning from 1% to 20%, 1% to 10%, 1% to 5%, 5% to 20%, 5% to 10%, and 10% to 20%.
  • extract means a compound or group of compounds that has been extracted from an extract source.
  • an extract source may be a plant (e.g., hemp, cannabis, kratom, kava, Kanna) or a fungus (e.g., mushrooms, cordyceps, lion mane, reishi, chaga gano, psilocybin mushrooms, etc.).
  • An extract may be extracted from the extract source as a full spectrum extract, a broad spectrum extract, a distillate, or an isolate.
  • Full-spectrum extracts can be made a variety of different ways known in the art, including through pressure along (e.g., using a press, such as a rosin press), solvent extraction (using an appropriate solvent, such as, ethanol, ether, ethyl acetate, acetone, low and medium chain hydrocarbon solvents, etc.), supercritical CO2 extraction, and the like. Where solvent extraction is used, extract can be collected by removing the extraction solvent medium. Broad spectrum extracts are more refined than full spectrum extracts. Broad spectrum extracts may be made by further purifying full spectrum extracts, removing particular agents from full spectrum extracts, etc.
  • Distillates may be made using methods known in the art, including extracting a full or broad spectrum extract and, optionally performing vacuum filtration to remove insoluble, and preforming a distillation.
  • a distillate may be collected by directly subjecting a source to distillation conditions.
  • An isolate is a single compound that has been isolated in a purified form (including substantially pure forms or pure form).
  • a “therapeutic ingredient” is a compound or group of compounds provided within a composition or as a composition that provides a therapeutic benefit.
  • a therapeutic ingredient in a particular composition may be an extract, a therapeutic agent, or a group of therapeutic agents.
  • a “therapeutic agent” is a compound that provides a therapeutic benefit.
  • One or more therapeutic agents may be combined to provide a therapeutic ingredient in a composition.
  • the “entourage effect” is a mechanism by which the combination of therapeutic agents in extracts or therapeutic ingredients act synergistically to modulate or treat a disease or disorder or exert a therapeutic benefit.
  • the term “cannabinoid” refers to the chemical substance, regardless of structure or origin, that joins the cannabinoid receptors of the body and brain and that have similar effects to those produced by the cannabis plant.
  • the term “cannabinoid” includes but is not limited to Cannabichromenes (e.g., cannabichromene (CBC), cannabichromenic acid (CBCA), cannabichromevarin (CBCV), cannabichromevarinic acid (CBCVA)), Cannabicyclols (e.g., cannabicyclol (CBL), cannabicyclolic acid (CBLA), cannabicyclovarin (CBLV), etc.), Cannabidiols (e.g., cannabidiol (CBD), cannabidiol monomethylether (CBDM), cannabidiolic acid (CBDA), Cannabidiol-C4 (CBD-C4), cannabidiol-C4 (CBD
  • Cannabinoids can also include cannabinoids derived from sources other than hemp or marijuana, such as oranges. Cannabinoids can also include synthetic (e.g., not naturally occurring, such as analogs, or naturally occurring but synthesized in a lab) chemicals.
  • the term “phytocannabinoid” refers to a group of cannabinoids that occur naturally in the cannabis plant, including but not limited to, THC (tetrahydrocannabinol), THCA (tetrahydrocannabinolic acid), CBD (cannabidiol), CBDA (cannabidiolic acid), CBN (cannabinol), CBG (cannabigerol), CBC (cannabichromene), CBL (cannabicyclol), CBV (cannabivarin), THCV (tetrahydrocannabivarin), CBDV (cannabidivarin), CBCV (cannabichromevarin), CBGV (cannabigerovarin), CBGM (cannabigerol monomethyl ether), CBE (cannabielsoin), and CBT (cannabicitran).
  • THC tetrahydrocannabinol
  • THCA tetrahydrocannabinolic acid
  • CBD canannabidio
  • phospholipid refers to a lipid having two hydrophobic fatty acid tails and a hydrophilic head comprising of a phosphate group.
  • short chain triglyceride refers to tri-substituted triglycerides with fatty acids having aliphatic tails of 1 to 5 carbon atoms (1, 2, 3, 4, 5) and mixtures thereof.
  • medium chain triglyceride refers to tri-substituted triglycerides with fatty acids having aliphatic tails of 6 to 12 carbon atoms (6, 7, 8, 9, 10, 11, 12) and mixtures thereof.
  • long chain triglyceride refers to tri-substituted triglycerides with fatty acids having an aliphatic tail of greater than 13 carbon atoms (13, 14, 15, 16, 17, 18, 19, 20, or more) and mixtures thereof.
  • sterol refers to a subgroup of steroids with a hydroxyl group at the 3-position of the A-ring.
  • Cmax is given its plain and ordinary meaning and refers to the maximum (or peak) plasma concentration of an agent after it is administered.
  • Tmax is given its plain and ordinary meaning and refers to the length of time required for an agent to reach maximum plasma concentration after the agent is administered.
  • AUC is given its plain and ordinary meaning and refers to the calculated area under the curve, referring to a plasma concentration-time curve (e.g., the definite integral in a plot of drug concentration in blood plasma vs. time.).
  • polydispersity or “PDI” is used to describe the degree of nonuniformity of a size distribution of particles. Also known as the heterogeneity index, PDI is a number calculated from a two-parameter fit to the correlation data (the cumulants analysis). This index is dimensionless and scaled such that values smaller than 0.05 are mainly seen with highly monodisperse standards.
  • an “amino acid” includes amino acids with natural amino acid side chains or non-natural amino acid side chains.
  • a “natural amino acid side chain” refers to the side-chain substituent of a naturally occurring amino acid.
  • Naturally occurring amino acids have a substituent attached to the a-carbon.
  • Naturally occurring amino acids include Arginine, Lysine, Aspartic acid, Glutamic acid, Glutamine, Asparagine, Histidine, Serine, Threonine, Tyrosine, Cysteine, Methionine, Tryptophan, Alanine, Isoleucine, Leucine, Phenylalanine, Valine, Proline, and Glycine.
  • Non-natural amino acid side chain refers to the side-chain substituent of a non-naturally occurring amino acid.
  • Non-natural amino acids include P-amino acids (P 3 and p 2 ), Homoamino acids, Proline and Pyruvic acid derivatives, 3-substituted Alanine derivatives, Glycine derivatives, Ring-substituted Phenylalanine and Tyrosine Derivatives, Linear core amino acids and N-methyl amino acids.
  • Exemplary non-natural amino acids are available from Sigma- Aldridge, listed under “unnatural amino acids & derivatives.” See also, Travis S. Young and Peter G. Schultz, “Beyond the Canonical 20 Amino Acids: Expanding the Genetic Lexicon,” J. Biol. Chem. 2010 285: 11039-11044, which is incorporated by reference in its entirety.
  • Kombucha is one example of a functional beverage that is seeing a surge in popularity due to its purported health benefits.
  • Kombucha sometimes called kombucha tea or kombucha broth, is a fermented, lightly effervescent, sweetened black or green tea drink.
  • Kombucha begins as a mixture of ordinary black tea sweetened with processed sugar.
  • a starter culture (called a SCOBY or Symbiotic Culture of Bacteria and Yeast) is added to the mixture, and the mixture is allowed to sit for a week to ten days to ferment at room temperature. By the end of this first fermentation period the mixture has transformed into kombucha, which is tart due to the presence of acetic acid and gluconic acid.
  • kombucha contains enzymes and amino acids, polyphenols, and various other organic acids which can very between preparations.
  • the variations in both chemical and microbial composition of the beverage can be observed owing to differences in tea varieties (black, green, and geographical origin), microbial culture conditions, process technologies, and duration of fermentation. These variations produce beverages of diverse functional properties.
  • supplemental sugars such as fruit or processed sugar is added after primary fermentation.
  • the kombucha may go through a second fermentation process in either bottles or kegs, where the residual yeast and bacteria consume the sugars and create natural carbonation.
  • the kombucha drink in some instances can contain ethanol.
  • the ethanol content can be more than 0.01 wt.%, more than 0.05 wt.%, more than 0.1 wt.%, more than 0.2 wt.%, more than 0.3 wt.%, more than 0.4 wt.%, more than 0.5 wt.%, more than 0.6 wt.%, more than 0.7 wt.%, more than 0.8 wt.%, more than 0.9 wt.%, more than 1 wt.%, more than 2 wt.%, more than 3 wt.%, more than 4 wt.%, more than 5 wt.%, more than 6 wt.%, more than 7 wt.%, more than 8 wt.%, more than 9 wt.%, more than 10 wt.%.
  • the kombucha drink contains 0.1 to 0.5 wt.%, 0.1 to 1 wt.%, 0.1 to 2 wt.%, 0.1 to 3 wt.%, 0.1 to 4 wt.%, 0.1 to 5 wt.%, 0.1 to 0.6 wt.%, 0.1 to 0.7 wt.%, 0.1 to 0.80 wt.%, 0.1 to 0.9 wt.%, 0.4 to 1 wt.%, 0.4 to 2 wt.%, 0.4 to 3 wt.%, 0.4 to 4 wt.%, 0.4 to 5 wt.%, 0.4 to 6 wt.%, 0.4 to 7 wt.%, 0.4 to 8 wt.%, 0.4 to 9 wt.%, 0.4 to 10 wt.%, or 0.01 to 10 wt.% ethanol or any amount or range thereof.
  • kombucha is a potential source of probiotics; kombucha may provide the benefits of green tea; kombucha contains antioxidants; kombucha can kill bacteria; kombucha may reduce heart disease risk; kombucha may help manage type 2 diabetes; and kombucha may help protect against cancer.
  • kombucha has exhibited a strong antimicrobial effect against Staphylococcus epidermidis, Micrococcus lutes, Listeria monocytogenes, and Pseudomonas aeruginosa. Because kombucha provides a unique delivery method with added health benefits there have been attempts to supplement the beverage with additional therapeutic ingredients (e.g., CBD). However, these attempts often fail due to the somewhat harsh environment provided by kombucha beverages. For instance, the therapeutic ingredient may degrade over time, causing it to lose efficacy.
  • additional therapeutic ingredients e.g., CBD
  • lipid-based particle composition that can deliver therapeutic ingredients (including extracts, therapeutic agents, and combinations of therapeutic agents) in fermented beverages, such as caffeinated alcoholic beverages (e.g., kombucha).
  • the therapeutic ingredients are provided in a solubilizing particle delivery system (e.g., lipid nanoparticle, a liposomal system, oil-in-water emulsions, dry liposome particles, etc.).
  • lipid-based particle compositions comprising extracts, therapeutic agents, or combinations of therapeutic agents.
  • the lipid- based particle composition is provided as a suspension in solution (e.g.
  • the disclosed lipid-based particle compositions achieve one or more of the following benefits (or other benefits): they include less impurities, they have less variations batch-to-batch (e.g., stability, degradation profiles, efficacy), they have more delivery predictability, they less side effects when treating a patient, they have higher bioavailability, they have faster onset of activity, they have better efficacy, they have better shelf-life, they have better stability in the gut, etc.
  • benefits include less impurities, they have less variations batch-to-batch (e.g., stability, degradation profiles, efficacy), they have more delivery predictability, they less side effects when treating a patient, they have higher bioavailability, they have faster onset of activity, they have better efficacy, they have better shelf-life, they have better stability in the gut, etc.
  • the beverage is an alcoholic beverage.
  • the beverage is an alcoholic beverage that is not kombucha.
  • the beverage in some instances can contain ethanol at more than 0.01 wt.%, more than 0.05 wt.%, more than 0.1 wt.%, more than 0.2 wt.%, more than 0.3 wt.%, more than 0.4 wt.%, more than 0.5 wt.%, more than 0.6 wt.%, more than 0.7 wt.%, more than 0.8 wt.%, more than 0.9 wt.%, more than 1 wt.%, more than 2 wt.%, more than 3 wt.%, more than 4 wt.%, more than 5 wt.%, more than 6 wt.%, more than 7 wt.%, more than 8 wt.%, more than 9 wt.%, more than 10 wt.%, more than 11 wt.%, more
  • the alcoholic beverage contains 0.1 to 0.5 wt.%, 0.1 to 1 wt.%, 0.1 to 2 wt.%, 0.1 to 3 wt.%, 0.1 to 4 wt.%, 0.1 to 5 wt.%, 0.1 to 0.6 wt.%, 0.1 to 0.7 wt.%, 0.1 to 0.80 wt.%, 0.1 to 0.9 wt.%, 0.4 to 1 wt.%, 0.4 to 2 wt.%, 0.4 to 3 wt.%, 0.4 to 4 wt.%, 0.4 to 5 wt.%, 0.4 to 6 wt.%, 0.4 to 7 wt.%, 0.4 to 8 wt.%, 0.4 to 9 wt.%, 0.4 to 10 wt.%, or 0.01 to 10 wt.% ethanol or any amount or range thereof.
  • the beverage in some instances can contain probiotics, such as yeast, bacteria, etc.
  • the probiotics are yeast.
  • the probiotics are bacteria.
  • the beverage is a kefir, a ginger beer, a kvass, a lacto-fermented soda, a rejuvelac, cultured vegetable juices, a beer, a probiotic shot, a soda, a probiotic soda, a probiotic seltzer, a yogurt drink, a hard seltzer, a hard lemonade, a cocktail, a infused water, a cider, a wine, a sake, a huangjiu, etc.
  • therapeutic lipid-based particle products comprising therapeutic ingredients.
  • the therapeutic ingredient are ingredients use or have used the thoroughness and diligence of pharmaceutical drug development to consumer products to be considered a therapeutic agent.
  • a nano-lipid delivery system is utilized to impart apparent aqueous solubility and deliverability to an otherwise practically water insoluble molecule (e.g., hemp, cannabis, fungus (e.g., mushrooms), kratom, kava, and Kanna derived hydrophobic phytocannabinoids and therapeutic molecules).
  • attributes of some embodiments disclosed herein have been determined to be high quality and reproducible. Such reproducibility and low variations may allow the products to generate a reproducible certificate of analysis for different batches.
  • the systems disclosed herein increase the bioavailability of therapeutic ingredients (e.g., CBD, cannabinoids, hemp extracts, cannabis extracts, fungus extracts, kratom extracts, kava extracts, Kanna extracts, other therapeutic agents, and/or combinations of any of the foregoing), decrease the time for absorption of those therapeutic ingredients, increase the stability of the therapeutic ingredients or the particles comprising the therapeutic ingredients, increase the consistency of delivery (e.g., by limiting batch-to-batch variation), and/or increase the efficacy of the therapeutic ingredients (higher dosing and/or faster onset of activity).
  • the compositions disclosed herein may deliver broad or full spectrum extracts and/or distillates to achieve an entourage effect, providing a synergy between active agents within the therapeutic ingredient.
  • the carriers (lipid-based particle compositions) disclosed herein are able to deliver therapeutic agents that are highly pure.
  • the therapeutic agents e.g., one or more cannabinoids, such as CBD, non-cannabinoids, hemp isolates, cannabis isolates, fungus isolates, kratom isolates, kava isolates, Kanna isolates, and combinations thereof
  • the therapeutic agents have a purity of greater than or equal to about: 90%, 95%, 98%, 99%, 99.5%, 99.9%, 99.99%, or ranges including and/or spanning the aforementioned values.
  • the lipid-based particle compositions disclosed herein make use of CBD or other therapeutic agents that are of sufficient purity that they exist as a solid (e.g., a powder, a crystalline compound, etc.).
  • the solid therapeutic agents are solid due to high levels of purity and lacking other agents that would cause it to form an oil when impure.
  • the CBD powder (or other therapeutic agents) lack solidifying agents, such as, maltodextrin or other additive agents that cause the solidification of CBD (or other therapeutic agents).
  • some embodiments relate to delivery systems (e.g., lipid-based particle compositions and/or formulations comprising the same) that improve the absorption of the highly insoluble forms of a therapeutic agent (e.g., hemp isolates, cannabis isolates, fungus isolates, kratom isolates, kava isolates, Kanna isolates, etc.) or combinations of agents.
  • a therapeutic agent e.g., hemp isolates, cannabis isolates, fungus isolates, kratom isolates, kava isolates, Kanna isolates, etc.
  • the therapeutic ingredient is a hemp extract, cannabis extract, fungus extract, kratom extract, kava extract, Kanna extract, or a combination thereof.
  • an extract can be a full spectrum extract, a broad spectrum extract, a distillate from a source, an isolate from plant or fungus source, and/or combinations thereof.
  • the therapeutic ingredient can comprise a mixture of different agents provided as an extract.
  • the therapeutic ingredient can be isolates from an extract, including single compounds (e.g., single active agents that are pure or substantially pure) or combinations of individual compounds (e.g., different active agents that, taken individually, are pure or substantially pure) that are mixed together (e.g., at different ratios) to provide the therapeutic agent of the delivery system.
  • the therapeutic ingredient e.g., hemp extract, cannabis extract, fungus extract, kratom extract, kava extract, Kanna extract, etc.
  • therapeutic agent used to prepare the lipid-based particle compositions disclosed herein e.g., the starting material
  • one or more or all of the therapeutic agents in the composition has an aqueous solubility of less than or equal to about: 0.05 mg/ml, 0.01 mg/ml, 0.012 mg/ml, 0.001 mg/ml, or ranges including and/or spanning the aforementioned values.
  • the aqueous solubility of the therapeutic agent or agents can be improved to equal to or greater than about: 1 mg/ml, 5 mg/ml, 20 mg/ml, 30 mg/ml, 50 mg/ml, 100 mg/ml, or ranges including and/or spanning the aforementioned values.
  • At least one therapeutic agent in the lipid-based particle composition is hydrophobic.
  • at least one hydrophobic therapeutic agent used to prepare a lipid-based particle composition as disclosed herein e.g., cannabinoid, a phytocannabinoid, vitamin, or other therapeutic agent, etc.
  • the solubility of the at least one hydrophobic therapeutic agent (and/or the amount of the therapeutic that can be provided in an aqueous solution) used to prepare the compositions disclosed herein can be improved to equal to or greater than about: 1 mg/ml, 5 mg/ml, 20 mg/ml, 30 mg/ml, 50 mg/ml, 100 mg/ml, or ranges including and/or spanning the aforementioned values.
  • the solubility of the at least one hydrophobic therapeutic agent can be improved by at least about: 50%, 100%, 150%, 200%, 500%, 1000%, 10,000%, or ranges including and or spanning the aforementioned values.
  • the solubility is measured as an amount that can be suspended for longer than 30 days and or that can be dissolved in an aqueous solution at a concentration of at least 20 mg/ml.
  • the therapeutic agent(s) is or may be synthetic. In several embodiments, as disclosed elsewhere herein, the therapeutic agent(s) is or may be non-synthetic. In several embodiments, as disclosed elsewhere herein, the therapeutic agent(s) is or may be semi- synthetic (e.g., prepared through fermentation, etc.).
  • the therapeutic ingredient is or may be a combination of synthetic and non-synthetic therapeutic agents.
  • the therapeutic ingredient is a single compound (or is substantially pure single compound).
  • the therapeutic ingredient comprises a mixture of different compounds (e.g., comprises a full spectrum of compounds from an extract, a mixture of isolates, etc.).
  • the therapeutic ingredient is an extract from a therapeutic agent source (e.g., cannabinoids, alkaloids, terpenes, or other therapeutics extracted from a source, such as a plant or mushroom).
  • the therapeutic ingredient is an extract or a mixture of extracts from one or more therapeutic agent sources.
  • the therapeutic ingredient is a distillate or a mixture of distillates from one or more therapeutic agent sources.
  • the therapeutic ingredient comprises a hemp extract, a fungus extract, a kratom extract, a kava extract, a Kanna extract, or combinations thereof.
  • the therapeutic ingredient is a cannabinoid distillate from a cannabinoid source.
  • the therapeutic ingredient is a vitamin, nutrient, plant extract, nutraceutical, pharmaceutical, or other beneficial agents for delivery.
  • the therapeutic ingredient may be an analgesic, an anesthetic, an antibacterial agent, an anticonvulsant, an antidementia agent, an antidepressant, an antidote, a deterrent, a toxicologic agent, an antiemetic, an antifungal, an antigout agent, an anti-inflammatory agent, an antimigraine agent, an antimyasthenic agent, an antineoplastic agent, an antiparasitic agent, an antiparkinson agent, an antipsychotic, an antipasticity agent, an antiviral, an anxiolytic, a bipolar agent, a blood glucose regulator, a blood product, a blood modifier, a blood volume expander, a cardiovascular agent, a central nervous system agent, a dental agent, an oral agent, a dermatological agent, an enzyme replacement agent, an enzyme modifying agent
  • the hormonal agent, a hormone stimulant, a hormone replacement, a hormone modifying agent, and/or hormone suppressant may act on the adrenal system, the pituitary system, the prostaglandin system, sex hormone, the thyroid, and/or the parathyroid.
  • the compound may comprise a small molecule.
  • the active compound may comprise a biologic.
  • the active compound may comprise a biomolecule.
  • the active compound may comprise a macromolecule.
  • the active compound comprises a nucleic acid, a protein, a lipid, a carbohydrate, or a combination thereof.
  • the active compound comprises a cell or a derivative of a cell.
  • the active compound comprises antisense RNA.
  • the active compound comprises an siRNA, a miRNA, a IncRNA, or a combination thereof.
  • the active compound comprises a nucleic acid vector.
  • the active compound is selected from the group consisting of Dihydromyrciten, a Vitamin, CoQlO, an Omega 3 fatty acid, Huperzine A, Bacopa monnieri extract, Cannabidiol, Cannabigerol, Cannabinol, Cannabichromene, Tetrahydrocannabivarin, Tetrahydrocannabinol, Full extracts of hemp, Specific ratios of isolated cannabinoids, Cannabigerolic acid, Cannabidolic acid, Mitragynine, Payantheine, Mitraphylline, Speciociliantine, Speciogynine, Cholecalciferol, Ergocalciferol, D,L-Alpha- Tocopherol, Menaquinone, Ascorbyl palmitate, Retinyl palmitate, Beta-Sitosterol, Plant Sterol Rich Extracts, Cholesterol, Ubiquinone, Phosphatidyl
  • the dry weight % of one or more therapeutic agents present in the composition is equal to or at least about: 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 50%, 60%, 70%, or ranges including and/or spanning the aforementioned values.
  • the therapeutic agents are provided in an aqueous composition.
  • the wet weight % of the one or more therapeutic agents present in the composition is equal to or at least about: 0.01%, 0.05%, 0.1%, 0.5%, 0.75%, 1%, 1.5%, 2%, 3%, 4%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values.
  • the one or more therapeutic agents may be provided in the wet composition at a concentration of greater than or equal to about: 0.1 mg/ml, 0.5 mg/ml, 1 mg/ml, 5 mg/ml, 20 mg/ml, 30 mg/ml, 50 mg/ml, 100 mg/ml, 150 mg/ml, 200 mg/ml, or ranges including and/or spanning the aforementioned values.
  • the dry weight % therapeutic ingredient present in the composition is equal to or at least about: 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 50%, 60%, 70%, or ranges including and/or spanning the aforementioned values.
  • the therapeutic ingredient is provided in an aqueous composition.
  • the wet weight % of the therapeutic ingredient present in the composition is equal to or at least about: 0.01%, 0.05%, 0.1%, 0.1%, 0.5%, 0.75%, 1%, 1.5%, 2%, 3%, 4%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values.
  • the therapeutic ingredient may be provided in the wet composition at a concentration of greater than or equal to about: 0.1 mg/ml, 0.5 mg/ml, 1 mg/ml, 5 mg/ml, 20 mg/ml, 30 mg/ml, 50 mg/ml, 100 mg/ml, 150 mg/ml, 200 mg/ml, or ranges including and/or spanning the aforementioned values.
  • the one or more therapeutic agents used in the lipid-based particle compositions as disclosed herein has high purity as indicated by its existing in a solid form (e.g., powder) prior to processing (e.g., formulation into a composition as disclosed herein).
  • a composition comprising one or more therapeutic agents (e.g., cannabinoids, such as CBD, non-cannabinoids, and combinations thereof) in water is provided.
  • cannabinoids such as CBD, non-cannabinoids, and combinations thereof
  • the delivery system may be lipid-based and forms an oil-in-water emulsion (e.g., a nanoemulsion), a liposome, and/or solid lipid particle (e.g., nanoparticle).
  • the lipid-based delivery system provides particles in the nano-measurement range (as disclosed elsewhere herein).
  • a solid lipid nanoparticle is spherical or substantially spherical nanoparticle.
  • a solid lipid nanoparticle possesses a solid lipid core matrix that can solubilize lipophilic molecules.
  • the lipid core is stabilized by surfactants and/or emulsifiers as disclosed elsewhere herein, while in other embodiments, surfactants are absent.
  • the size of the particle is measured as a mean diameter. In several embodiments, the size of the particle is measured by dynamic light scattering. In several embodiments, the size of the particle is measured using a zeta-sizer. In several embodiments, the size of the particle can be measured using Scanning Electron Microscopy (SEM). In several embodiments, the size of the particle is measured using a cryogenic SEM (cryo-SEM). Where the size of a nanoparticle is disclosed elsewhere herein, any one or more of these instruments or methods may be used to measure such sizes.
  • the lipid-based particle and/or nanoparticle composition (e.g., a liposomal composition as disclosed herein, a solid lipid particle composition as disclosed herein, an oil-in-water emulsion composition as disclosed herein, etc.), or simply the composition for brevity, comprises a therapeutic agent or combination of therapeutic agents (e.g., one or more cannabinoids, phytocannabinoids, non-cannabinoid therapeutics) and one or more of a phospholipid, a lipid other than a phospholipid (e.g., a lipid that is not a phospholipid), and a sterol.
  • therapeutic agents e.g., one or more cannabinoids, phytocannabinoids, non-cannabinoid therapeutics
  • a phospholipid e.g., a lipid other than a phospholipid
  • a lipid that is not a phospholipid e.g., a lipid that is not a phospholipid
  • the composition comprises, consists of, or consists essentially of therapeutic agent or combination of therapeutic agents (e.g., one or more cannabinoids, phytocannabinoids, non-cannabinoid therapeutics, hemp extracts, cannabis extracts, fungus extracts, kratom extracts, kava extracts, Kanna extracts, etc.), a phospholipid, a lipid other than a phospholipid (e.g., a lipid that is not a phospholipid), and a sterol.
  • the composition is aqueous (e.g., contains water) while in other embodiments, the composition is dry (lacks water or substantially lacks water).
  • the composition has been dried (e.g., has been subjected to a process to remove most or substantially all water).
  • the composition comprises nanoparticles in water (e.g., as a solution, suspension, or emulsion).
  • the composition is provided as a powder (e.g., that can be constituted or reconstituted in water).
  • the water content (in wt %) of the composition is less than or equal to about: 21%, 20%, 15%, 10%, 5%, 2.5%, 1%, 0.5%, 0.1%, or ranges including and/or spanning the aforementioned values.
  • the lipid-based particle composition may include one or more therapeutic agents (e.g., a single therapeutic agent or a combination of therapeutic agents) as a therapeutic ingredient.
  • the lipid-based particle composition may include a single therapeutic agent or a plurality of therapeutic agents (e.g., 1, 2, 3, 4, or more).
  • the lipid-based particle composition may include a single therapeutic extract or a plurality of therapeutic extracts (e.g., 1, 2, 3, 4, or more).
  • the lipid-based particle composition may comprise a cannabinoid and a non-cannabinoid therapeutic agent (e.g., a cannabinoid and a terpene); the lipid-based particle may comprise two cannabinoids and a non-cannabinoid therapeutic agent; the lipid-based particle may comprise two non-cannabinoid therapeutic agents; the lipid-based particle may comprise a non-cannabinoid, hydrophilic therapeutic agent and a hydrophobic active agent (e.g., a cannabinoid or non-cannabinoid); the lipid-based particle may comprise a hemp extract and a kava extract; the lipid-based particle may comprise a kava extract and a kanna extract; the lipid-based particle may comprise a mushroom extract and a kratom extract; the lipid-based particle may comprise a kratom extract and a hemp extract; the lipid-based particle may comprise a kratom extract and a kanna
  • the therapeutic agents are present in the aqueous lipid-based particle composition at a concentration of less than or equal to about: 200 mg/ml, 150 mg/mL, 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 2.5 mg/ml, 1 mg/ml, 0.5 mg/ml, 0.1 mg/ml or ranges including and/or spanning the aforementioned values.
  • the one or more therapeutic agents are present in the aqueous composition at a concentration of greater than or equal to about: 200 mg/ml, 150 mg/mL, 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 2.5 mg/ml, 1 mg/ml, 0.5 mg/ml, 0.1 mg/ml or ranges including and/or spanning the aforementioned values.
  • the one or more therapeutic agents are present in the composition at a dry wt % of equal to or at least about: 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 50%, 60%, 70%, or ranges including and/or spanning the aforementioned values.
  • the one or more therapeutic agents, collectively or individually are present in the composition at a wet wt % of equal to or at least about: 0.01%, 0.05%, 0.1%, 0.25%, 0.5%, 1%, 2%, 3%, 4%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values.
  • the composition is aqueous, while in others it has been dried into a powder (that is free of or substantially free of water). In several embodiments, where the composition has been dried, it comprises a water content of less than or equal to 20%, 15%, 10%, 7.5%, 5%, 2.5%, 1%, or ranges including and/or spanning the aforementioned values.
  • the therapeutic ingredient is present in the aqueous lipid- based particle composition at a concentration of less than or equal to about: 200 mg/ml, 150 mg/mL, 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 2.5 mg/ml, 1 mg/ml, 0.5 mg/ml, 0.1 mg/ml or ranges including and/or spanning the aforementioned values.
  • the therapeutic ingredient is present in the aqueous composition at a concentration of greater than or equal to about: 200 mg/ml, 150 mg/mL, 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 2.5 mg/ml, 1 mg/ml, 0.5 mg/ml, 0.1 mg/ml or ranges including and/or spanning the aforementioned values.
  • the therapeutic ingredient is present in the composition at a dry wt % of equal to or at least about: 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 50%, 60%, 70%, or ranges including and/or spanning the aforementioned values.
  • the therapeutic ingredient is present in the composition at a wet wt % of equal to or at least about: 0.01%, 0.05%, 0.1%, 0.25%, 0.5%, 1%, 2%, 3%, 4%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values.
  • the composition is aqueous, while in others it has been dried into a powder (that is free of or substantially free of water). In several embodiments, where the composition has been dried, it comprises a water content of less than or equal to 20%, 15%, 10%, 7.5%, 5%, 2.5%, 1%, 0.5%, 0.1%, 0.05%, 0.01%, or ranges including and/or spanning the aforementioned values.
  • the therapeutic ingredient may comprise, consist of, or consist essentially of a full spectrum or broad spectrum extract (e.g., hemp, fungus, kratom, Kanna, and kava extracts).
  • the therapeutic ingredient comprises rosin.
  • the rosin is extract that is produced after pressing cannabis or hemp flower or any botanical containing oily therapeutic agents using a high-pressure press.
  • the rosin is a full spectrum extract.
  • the therapeutic agent may comprise full spectrum extract, broad spectrum extract, crude, distillates, oils, and isolates, and combinations thereof.
  • the lipid-based particle composition may include one or more cannabinoids (e.g., a single cannabinoid or a combination of different cannabinoids).
  • the lipid-based particle composition may include one or more phytocannabinoids (e.g., a single phytocannabinoid or a combination of different phytocannabinoids).
  • the lipid-based particle composition comprises CBD and at least one other cannabinoid and/or therapeutic agent.
  • the lipid-based particle composition comprises a cannabichromene, a cannabicyclol, a cannabidiol, a cannabielsoin, a cannabigerol, a cannabinol, a cannabinodiol, a cannabitriol, a delta-9-tetrahydrocannabinol, another cannabinoid, a synthetic cannabinoid, and/or combinations of any of the foregoing.
  • the lipid-based particle composition comprises two or more cannabichromenes, cannabicyclols, cannabidiols, cannabielsoins, cannabigerols, cannabinols, cannabinodiols, cannabitriols, delta-9-tetrahydrocannabinols, tetrahydrocannabiphorols, cannabidiolphorols, other cannabinoids, synthetic cannabinoids, and/or combinations of any of the foregoing.
  • the lipid-based particle composition comprises CBC, CBCA, CBCV, CBCVA, CBL, CBLA, CBLV, CBD, CBDM, CBDA, CBD-C1, CBDV, CBDVA, CBEA-B, CBE, CBEA-A, CBG, CBGM, CBGA, CBGAM, CBGV, CBGVA, CBND, CBVD, CBN, CBNM, CBN-C2, CBN-C4, CBNA, CBN-C1, CBV, CBDP, THCP, 10-ethoxy-9-hydroxy-delta-6a-tetrahydrocannabinol, 8,9-dihydroxy-delta-61- tetrahydrocannabinol, CBT, CBTV, THC, THC-C4, THCA-A, THCA-B, THCA-C4, THC- Cl, THCA-C1, THCV, THCVA, OTHC, CBCF, CBF, cannabigl
  • the lipid-based particle composition comprises CBN, CBD, and CBG.
  • the cannabinoid or cannabinoids collectively or individually, are present in the aqueous lipid-based particle composition at a concentration of less than or equal to about: 200 mg/ml, 150 mg/ml, 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 2.5 mg/ml or ranges including and/or spanning the aforementioned values.
  • the cannabinoid or cannabinoids are present in the aqueous composition at a concentration of greater than or equal to about: 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, or ranges including and/or spanning the aforementioned values.
  • the cannabinoid or cannabinoids, collectively or individually are present in the composition at a dry wt % of equal to or at least about: 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 50%, 60%, 70%, or ranges including and/or spanning the aforementioned values.
  • the cannabinoid or cannabinoids are present in the composition at a wet wt % of equal to or at least about: 0.1%, 0.25%, 0.5%, 1%, 2%, 3%, 4%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values.
  • the total potential THC does not to exceed 0.3 weight % of the phytocannabinoid, where the total potential THC is defined as THCa x 0.877 + 9- THC + 8-THC.
  • the total potential THC does not to exceed 0.3 weight % of the phytocannabinoid, where the total potential THC is defined as THCa + 9-THC.
  • the lipid-based particle composition may comprise a non-cannabinoid therapeutic agent or non-cannabinoid active agents (e.g., agents that are not a cannabinoid).
  • the therapeutic e.g., non-cannabinoid therapeutic agent
  • the therapeutic agent is hydrophilic.
  • the therapeutic agent is hydrophobic.
  • the therapeutic agent e.g., non-cannabinoid therapeutic
  • the non-cannabinoid therapeutic agent is selected from the group consisting of Noopept (N-phenylacetyl-L-prolyglygice ethyl ester), melatonin, glutathione, gamma-glutamylcysteine (GGC), gamma-aminobutyric acid (GABA), valerian root, magnesium, theanine, 5-HTP, tyrosine, taurine, zinc, alpha fenchone, alpha terpinene, alpha terpineol, beta caryophyllene, alpha pinene, beta pinene, bisabolene, bisabolol, borneol, eucalyptol, gamma terpinene, guaiacol, humulene, linalool, myrcene, para cymene, phytol, terpinolene, limonene, others, and/or
  • these non-cannabinoid therapeutic agents may be provided in combination with cannabinoids at the concentrations disclosed herein.
  • a hydrophilic composition when used, it is mixed with the aqueous soluble ingredients before mixing with the lipid ingredients.
  • the lipid particles comprise extracts of mushrooms (e.g., cordyceps, lion mane, reishi, chaga gano, psilocybin (including the compound itself, natural extract forms, synthetic forms, derivatives of psilocybin, and prodrugs of any one of the foregoing), others, and/or combinations of any of the foregoing), kratom extracts, Kanna extracts, kava extracts, or combinations of any one or more of the foregoing.
  • Such combination of extracts may also include any of the foregoing and hemp and marijuana extracts as disclosed herein.
  • the therapeutic ingredient is an extract as disclosed herein.
  • the lipid particle is composed of or comprises individual compounds (e.g., therapeutic agents) from any of the extracts disclosed herein (e.g., mushrooms, kratom, Kanna, kava, hemp, marijuana, combinations thereof, etc.).
  • the therapeutic agents are highly pure isolates derived from mushrooms, kratom, Kanna, kava, hemp, marijuana, or combinations of any of the foregoing.
  • These compounds (e.g., therapeutic agents) may also be from other sources, for example, sources that provide these therapeutic compounds but that are other natural sources (other than mushrooms, kratom, Kanna, kava, hemp, marijuana, etc.).
  • the compounds are derived from or are broad spectrum extracts (e.g., oils, etc.), full spectrum extracts (e.g., oils, etc.), distillates (e.g., oils, etc.), and/or combinations thereof.
  • the lipid particles are composed of or comprise compounds (e.g., therapeutic agents) from a crude extract (an extract that is not further purified).
  • the lipid particle is composed of compounds (e.g., therapeutic agents) from combinations of sources.
  • the lipid particles are composed of or comprise extracts of mushrooms (e.g., cordyceps, lion mane, reishi, chaga gano, psilocybin (including the compound itself, natural extract forms, synthetic forms, derivatives of psilocybin, and prodrugs of any one of the foregoing), others, and/or combinations of any of the foregoing).
  • the therapeutic ingredient comprises, consists of, or consists essentially of a fungus extract.
  • the lipid particles disclosed herein are composed and/or comprise fungus extracts (e.g., a mushroom extract) including individual compounds (e.g., therapeutic compounds) from fungus, isolates from fungus, distillates from fungus, broad spectrum extracts from fungus, and/or full spectrum extracts from fungus.
  • the therapeutic ingredient comprises, consists of, or consists essentially of a mushroom extract or fungus extract.
  • the therapeutic ingredient is an active agent or a combination of active agents from a mushroom or a mushroom extract.
  • lipid particles are composed and/or comprise mushroom extracts (e.g., of mushroom powder or oil).
  • the mushroom extracts include extracts from a mushroom species that produces psilocybin (e.g., a psilocybin mushroom).
  • the mushroom species is selected from the group consisting of Mitragyna speciosa, Mitragyna Hirsuta, Mitragyna Javanica, Psilocybe azurescens, Psilocybe semilanceata, Psilocybe cyanescens, or combinations thereof.
  • the mushroom extract is an alkaloid.
  • the mushroom extract and/or therapeutic agent is psilocin (3-[2 (dimethylamino)ethyl]-4-indolol), psilocybin ([3-(2- dimethylaminoethyl)-l//-indol-4-yl] dihydrogen phosphate), baeocystin, norbaeocystin, bufotenin, aeruginascin, or combinations of any of the foregoing.
  • the mushroom extracts are extracted from mushrooms (e.g., are natural extracts).
  • the mushroom extracts may be produced synthetically (e.g., in a laboratory).
  • the synthetic extract may share a structure with an extract that is naturally occurring.
  • the mushroom extracts are analogs of natural extracts of mushrooms (e.g., produced synthetically).
  • the lipid particles as disclosed herein are composed and or comprise kratom extracts, including individual compounds (e.g., therapeutic compounds) from kratom, isolates from kratom, distillates from kratom, broad spectrum extracts from kratom, and/or full spectrum extracts from kratom.
  • the therapeutic ingredient comprises, consists of, or consists essentially of a kratom extract.
  • the therapeutic ingredient is an active agent or a combination of active agents from kratom or a kratom extract.
  • the lipid particles are composed of and/or comprise kratom powders, kratom oils, and/or kratom active ingredients.
  • the kratom extracts are from one or more kratom strains.
  • the one or more kratom strains are selected from Maeng da, Indo, Bas/red vein, Green Malay, Super Green Malaysian, Red Kali Kratom, Green Vein Kali, White Vein Kali, Red Indo Kratom, Green Indo Kratom, White Vein Indo Kratom, White Vein Thai Kratom, Gold Reserve Kratom Extract, Ultra Enhanced Indo Extract, ISOL-8 Extract, Natural Enhanced True Thai, Natural Enhanced White Sumatra, other kratoms, or combinations of any of the foregoing.
  • the lipid particles are composed of and/or comprise of kratom extracts (e.g., one or more kratom extracts).
  • the kratom extract is selected from the group consisting of alkaloids, mitaphylline, 7-OH-mitragynine, paynantheine, speciogynine, mitragynine, mitrajavine, other kratom active agents, and/or combinations of any of the foregoing.
  • the kratom extract is an alkaloid.
  • the kratom extract is selected from the group consisting of ajmalicine or raubasine (e.g., a cerebrocirculant, antiaggregant, anti- adrenergic at alpha- 1, sedative, anticonvulsant, smooth muscle relaxer), akuammigine, ciliaphylline (e.g., an antitussive, analgesic), corynantheidine (p-opioid antagonist, also found in yohimbe), corynoxeine (e.g., a calcium channel blocker), corynoxine A and/or B (dopamine mediating anti-locomotives), epicatechin (e.g., an antioxidant, antiaggregant, antibacterial, antidiabetic, antihepatitic, anti-inflammatory, anti-leukemic, antimutagenic, antiperoxidant, antiviral, potential cancer preventative, alpha- amylase inhibitor), 9- hydroxycorynantheidine (e.g.,
  • the kratom extracts are extracted from kratom (e.g., are natural extracts). In other embodiments, the kratom extracts may be produced synthetically (e.g., in a laboratory). In several embodiments, the synthetic extract may share a structure with an extract that is naturally occurring. In several embodiments, the kratom extracts are analogs of natural extracts of kratom (e.g., produced synthetically).
  • the lipid particles as disclosed herein are composed and or comprise Sceletium extracts, including individual compounds (e.g., therapeutic compounds) from Sceletium, isolates from Sceletium, distillates from Sceletium, broad spectrum extracts from Sceletium, and/or full spectrum extracts from Sceletium.
  • the therapeutic ingredient is a Sceletium extract.
  • the therapeutic ingredient is an active agent or a combination of active agents from Sceletium or a Sceletium extract. Sceletium is a succulent plant commonly found in South Africa, which is also known as Kanna, Channa, Kougoed.
  • the lipid particles are composed of and/or comprise Sceletium powders, Sceletium oils, and/or Sceletium active ingredients.
  • the therapeutic ingredient comprises, consists of, or consists essentially of a Sceletium extract.
  • the therapeutic ingredient is an active agent or a combination of active agents from a Sceletium extract.
  • the Sceletium extracts are from one or more Sceletium species.
  • the one or more species are selected from the Tortuosum family (Sceletium tortuosum; Sceletium crassicaule; Sceletium strictum; Sceletium expansum, Sceletium varians, etc.) or the Emarcidum family (Sceletium emarcidum; Sceletium exalatum, Sceletium rigidum, etc.).
  • Tortuosum family Sceletium tortuosum; Sceletium crassicaule; Sceletium strictum; Sceletium expansum, Sceletium varians, etc.
  • Emarcidum family Sceletium emarcidum; Sceletium exalatum, Sceletium rigidum, etc.
  • combinations of Sceletium species are used, other Sceletium species, or combinations of any of the foregoing.
  • the lipid particles are composed of and/or comprise Sceletium extracts (e.g., one or more Sceletium extracts).
  • the lipid particles are composed of and/or comprise Sceletium powders and/or Sceletium active ingredients (e.g., including but not limited to alkaloids).
  • the Sceletium extract is an alkaloid.
  • the Sceletium extract is selected from the group consisting of joubertiamine dehydrojoubertiamine dihydrojoubertiamine joubertinamine, O-methyldehydrojoubertiamine, O- methyljouberiamine, O-methyldihydrojoubertiamine, 3’-methoxy-4’-o-methyl joubertiamine, 4-(3,4-dimehoxyphenyl)-4-[2-acetylmethylamino)ethyl]cyclohexanone, 4-(3-methoxy-4- hydroxy-phenyl)-4-[2-(aceylmethylamino)ethyl]cyclohexadienone, sceletium alkaloid A4, touruosamine, N-formyltortuosamine, N-acetyltortuosamine, or combinations of any of the foregoing.
  • the Sceletium extract is a 3a-aryl-cis-octahydroindole class (e.g. mesembrine), C-seco mesembrine alkaloids (e.g. joubertiamine), an alkaloid containing a 2,3 -disubstituted pyridine moiety and 2 nitrogen atoms (e.g. sceletium A4), a ring C-seco Sceletium alkaloid A4 group (e.g. tortuosamine), or combinations of the foregoing.
  • Sceletium extracts are extracted from Sceletium (e.g., are natural extracts).
  • Sceletium extracts may be produced synthetically (e.g., in a laboratory).
  • the synthetic extract may share a structure with an extract that is naturally occurring.
  • the Sceletium extracts are analogs of natural extracts of Sceletium (e.g., produced synthetically).
  • the lipid particles as disclosed herein are composed and/or comprise kava extracts, including individual compounds (e.g., therapeutic compounds) from kava, isolates from kava, distillates from kava, broad spectrum extracts from kava, and/or full spectrum extracts from kava.
  • the therapeutic ingredient comprises, consists of, or consists essentially of a kava extract.
  • the therapeutic ingredient is an active agent or a combination of active agents from kava or a kava extract.
  • the lipid particles are composed of and/or comprise kava powders, kava oils, and/or kava active ingredients (e.g., including but not limited to alkaloids).
  • Kava is Piper inelhy.slicum) is a plant found in the south Pacific.
  • the lipid particles are composed of and/or comprise of kava extracts (e.g., one or more kava extracts).
  • the kava extract is an alkaloid (pipermethystine, etc.), a kavalactone (e.g., dihydrokavain, kavain, desmehtoxyyangonin, dihydromethysticin, yangonin, methysticin, etc.) or combinations of any of the foregoing.
  • the kava extracts are extracted from kava plants (e.g., are natural extracts).
  • the kava extracts may be produced synthetically (e.g., in a laboratory).
  • the synthetic extract may share a structure with an extract that is naturally occurring.
  • the kava extracts are analogs of natural extracts of kava (e.g., produced synthetically).
  • the therapeutic agent or combination of therapeutic agents is present in the aqueous composition at a concentration of greater than or equal to about: 200 mg/ml, 150 mg/ml, 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 2.5 mg/ml, 1 mg/ml, 0.5 mg/ml, 0.1 mg/ml, or ranges including and/or spanning the aforementioned values.
  • the one or more therapeutic agent(s) are present in the composition at a dry wt % of equal to or at least about: 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 50%, 60%, 70%, or ranges including and/or spanning the aforementioned values.
  • the one or more therapeutic agent(s) are present in the composition at a wet wt % of equal to or at least about: 0.01%, 0.05%, 0.1%, 0.25%, 0.5%, 1%, 2%, 3%, 4%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values.
  • combination products are provided.
  • combination products may include one or more cannabinoids, one or more non-cannabinoid therapeutic agents, or mixtures of any the foregoing.
  • lipid-based particle compositions as disclosed herein may be configured for use as a sleep aid formulation, for use in methods of inducing sleep, and/or for methods of treating sleep disorders.
  • the lipid-based particle composition for use as a sleep aid comprises one or more of CBN, CBD, and/or CBG.
  • an aqueous sleep aid lipid-based particle composition comprises CBN in an amount equal to or less than about: 100 mg/ml, 75 mg/ml, 50 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, or ranges including and/or spanning the aforementioned values.
  • an aqueous sleep aid lipid-based particle composition comprises CBD in an amount equal to or less than about: 100 mg/ml, 75 mg/ml, 50 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 2 mg/ml, 1 mg/ml or ranges including and/or spanning the aforementioned values.
  • an aqueous sleep aid lipid-based particle composition comprises CBG in an amount equal to or less than about: 100 mg/ml, 75 mg/ml, 50 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 2 mg/ml, 1 mg/ml or ranges including and/or spanning the aforementioned values.
  • an aqueous sleep aid lipid-based particle composition comprises CBN in an amount equal to or less than about 20 mg/ml, CBD in an amount equal to or less than about 2 mg/ml, and CBG in an amount equal to or less than about 1 mg/ml. In several embodiments, an aqueous sleep aid lipid-based particle composition comprises CBN in an amount equal to or less than about 10 mg/ml, CBD in an amount equal to or less than about 2 mg/ml, and CBG in an amount equal to or less than about 1 mg/ml.
  • the sleep aid formulation comprises one or more of valerian root, magnesium, GABA, galantamine, melatonin, theanine, 5-HTP, tyrosine, taurine, zinc (e.g., non-cannabinoid therapeutic agents in the amounts as disclosed elsewhere herein). These ingredients may be provided in addition to CBN, CBD, and/or CBG or as alternatives to any one of these cannabinoids.
  • the sleep aid formulation comprises THC (in the amounts as disclosed elsewhere herein).
  • valerian root, magnesium, GABA, galantamine, melatonin, theanine, 5-HTP, tyrosine, zinc, and/or taurine may be provided in addition to one or more cannabinoid in several embodiments of sleep aid formulations.
  • the lipid-based particle composition comprising one or more of valerian root, magnesium, GABA, galantamine, melatonin, theanine, 5-HTP, tyrosine, taurine, zinc, and/or one or more cannabinoids is configured for use as a use in a method of treating insomnia or sleeplessness.
  • the sleep aid formulation comprises one or more of limonene, myrcene, alpha-terpinene, gamma-terpinene, linalool, and/or terpinolene maybe included (e.g., non-cannabinoid therapeutic agents in the amounts as disclosed elsewhere herein).
  • one or more cannabinoids e.g., CBN, CBD, CBG, etc.
  • CBN, CBD, CBG, etc. may be added to any one or more of limonene, myrcene, alpha-terpinene, gamma-terpinene, linalool, and/or terpinolene to provide a sleep aid formulation.
  • the lipid-based particle composition comprising one or more of limonene, myrcene, alpha- terpinene, gamma-terpinene, linalool, terpinolene, and/or one or more cannabinoids is configured for use as a use in a method of treating insomnia or sleeplessness.
  • the lipid-based particle composition comprises one or more of alpha-fenchome, guaiacel, para-cymene, and/or beta-camophyliene (e.g., non- cannabinoid therapeutic agents in the amounts as disclosed elsewhere herein).
  • the lipid-based particle composition comprising one or more of alpha- fenchome, guaiacel, para-cymene, and/or beta-camophyliene is configured for use as a pain relief formulation and/or is used in methods of treating pain.
  • the lipid-based particle composition comprising alpha-fenchome, guaiacel, para-cymene, and/or beta-camophyliene is configured for oral or topical use in pain relief (e.g., to treat pain).
  • alpha-fenchome, guaiacel, para-cymene, and/or beta-camophyliene may be provided with CBD or other cannabinoids (e.g., in the amounts disclosed elsewhere herein) or without cannabinoids.
  • the lipid-based particle composition comprises one or more of alpha-terpineol and/or phytol (e.g., non-cannabinoid therapeutic agents in the amounts as disclosed elsewhere herein).
  • the lipid-based particle composition comprising alpha-terpineol and/or phytol is configured for use as an anti-anxiety formulation (e.g., to treat anxiety) and/or is used in methods of treating anxiety.
  • alpha-terpineol and/or phytol may be provided with CBD or other cannabinoids (e.g., in the amounts disclosed elsewhere herein) or without cannabinoids.
  • the lipid-based particle composition comprises alpha- fenchome, alpha-terpineol, and/or bisabolol (in the amounts as disclosed elsewhere herein).
  • the lipid-based particle composition comprising alpha-fenchome, alpha-terpineol, and/or bisabolol is configured for use as an anti-inflammatory formulation and/or is used in a method of reducing and/or treating inflammation.
  • alpha-fenchome, alpha-terpineol, and/or bisabolol may be provided with CBD or other cannabinoids (e.g., in the amounts disclosed elsewhere herein) or without cannabinoids.
  • the lipid-based particle composition comprises one or more of alpha-terpineol and/or canephene.
  • the lipid-based particle composition comprising alpha-terpineol and/or canephene is configured for use as an antioxidant and/or is used in a method of lowering oxidative damage in the body of a subject.
  • alpha-terpineol and/or canephene may be provided with CBD or other cannabinoids (e.g., in the amounts disclosed elsewhere herein) or without cannabinoids.
  • the CBD or other therapeutic agent is a purified form.
  • the CBD or other therapeutic used to prepare the lipid-based particle composition is a solid and not an oil (e.g., is a CBD of sufficiently high purity that it exists as a solid).
  • the CBD (or other non-THC cannabinoid) is an isolate having a THC (including all THC isomers and stereoisomers) content (in weight %) of less than or equal to about: 0.01%, 0.1%, 0.3%, 0.5%, 1.0%, 3.0%, 4.0%, 5.0%, or ranges including and/or spanning the aforementioned values.
  • the CBD (or other non-THC cannabinoid) has a total potential THC content (in weight %) of less than or equal to about: 0.01%, 0.1%, 0.3%, 0.5%, 1.0%, 3.0%, 4.0%, 5.0%, or ranges including and/or spanning the aforementioned values.
  • the CBD (or other non-THC cannabinoid) is substantially THC free, lacks THC, or lacks a detectable amount of THC.
  • the CBD (or other non-THC cannabinoid) is isolated from hemp and/or marijuana.
  • the CBD (or other non-THC cannabinoid) is isolated from hemp and not marijuana.
  • the CBD (or other non-THC cannabinoid) is isolated from marijuana and not hemp.
  • the CBD (or other cannabinoid) has a terpene impurity content (in weight percent) of less than or equal to about: 0.01%, 0.1%, 0.3%, 0.5%, 1.0%, 2.0%, 5.0% or ranges including and/or spanning the aforementioned values.
  • the liquid solution or substantially solid composition of lipid particles is composed of cannabinoids that are highly pure isolates derived from hemp or marijuana plant. Cannabinoids may also be from other sources, for example, ones derived from terpenes and natural sources that do not include hemp. Examples include “citrus CBD” “terpene CBD” and pharmaceutical “synthetic” CBD.
  • the cannabinoids are derived from broad spectrum hemp and/or cannabis oil, full spectrum hemp and/or cannabis oil, distillates from hemp and/or cannabis oil and combinations thereof.
  • the lipid particles are composed of cannabinoids derived from resin or rosin (solventless extraction of cannabinoids achieved by pressing biomass).
  • the lipid particles are composed of cannabinoids from a crude extract of hemp or marijuana (an extraction that is not further purified).
  • the lipid particle solution is composed of cannabinoids from combinations of sources, such as hemp oil fortified with cannabinoid isolate.
  • the active compound comprises at least one antioxidant.
  • antioxidants that can be used with the compositions of the present invention include acetyl cysteine, ascorbic acid polypeptide, ascorbyl dipalmitate, ascorbyl methylsilanol pectinate, ascorbyl palmitate, ascorbyl stearate, BHA, BHT, t-butyl hydroquinone, cysteine, cysteine HCI, diamylhydroquinone, di-t-butylhydroquinone, dicetyl thiodipropionate, dioleyl tocopheryl methylsilanol, disodium ascorbyl sulfate, distearyl thiodipropionate, ditridecyl thiodipropionate, dodecyl gallate, erythorbic acid, esters of ascorbic acid, ethyl ferulate, ferulic acid, gall
  • the active compound comprises at least one essential oil.
  • Essential oils include oils derived from herbs, flowers, trees, and other plants. Such oils are typically present as tiny droplets between the plant’s cells, and can be extracted by several methods known to those of skill in the art (e.g., steam distilled, enfleurage, maceration, solvent extraction, or mechanical pressing). When these types of oils are exposed to air they tend to evaporate. As a result, many essential oils are colorless, but with age they can oxidize and become darker. Essential oils are insoluble in water and are soluble in alcohol, ether, fixed oils (vegetal), and other organic solvents. Typical physical characteristics found in essential oils include boiling points that vary from about 160 to 240 °C and densities ranging from about 0.759 to about 1.096.
  • Essential oils typically are named by the plant from which the oil is found.
  • rose oil or peppermint oil are derived from rose or peppermint plants, respectively.
  • Non-limiting examples of essential oils that can be used in the context of the present invention include sesame oil, macadamia nut oil, tea tree oil, evening primrose oil, Spanish sage oil, Spanish rosemary oil, coriander oil, thyme oil, pimento berries oil, rose oil, anise oil, balsam oil, bergamot oil, rosewood oil, cedar oil, chamomile oil, sage oil, clary sage oil, clove oil, cypress oil, eucalyptus oil, fennel oil, sea fennel oil, frankincense oil, geranium oil, ginger oil, grapefruit oil, jasmine oil, juniper oil, lavender oil, lemon oil, lemongrass oil, lime oil, mandarin oil, marjoram oil, myrrh oil, neroli oil, orange oil,
  • the active agent comprises an algae extract.
  • the algae extract may comprise ashwagandha and/or astoxantin.
  • the active compound is encapsulated by particle at a concentration of 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 105 mg, 110 mg, 115 mg, 120 mg, 125 mg, 130 mg, 135 mg, 140 mg, 145 mg, 150 mg, or ranges including and/or spanning the aforementioned values, per kg of the nanoparticle.
  • a lipid-based particle composition e.g., a liposomal, solid lipid particles, oil-in-water emulsions, nanoparticle, etc.
  • the lipid- based particle composition e.g., when in water or dried
  • the lipid- based particle composition comprises multilamellar particle vesicles, unilamellar particle vesicles, multivesicular particles, emulsion particles, irregular particles with lamellar structures and bridges, partial emulsion particles, combined lamellar and emulsion particles, and/or combinations thereof.
  • the composition is characterized by having multiple types of particles (e.g., lamellar, emulsion, irregular, etc.).
  • a majority of the particles present are emulsion particles.
  • a majority of the particles present are lamellar (multilamellar and/or unilamellar).
  • a majority of the particles present are irregular particles.
  • a minority of the particles present are emulsion particles.
  • a minority of the particles present are lamellar (multilamellar and/or unilamellar).
  • a minority of the particles present are irregular particles.
  • multilamellar particles comprise equal to or at least about 5%, 8%, 9%, 10%, 15%, 25%, 50%, 75%, 85%, 95%, or 100% (or ranges spanning and/or including the aforementioned values), of the particles present in the composition (e.g., the aqueous composition)
  • the composition e.g., the aqueous composition
  • between about 5% and about 10% of the particles present are multilamellar.
  • about 8.6% of the particles present are multilamellar.
  • unilamellar particles comprise equal to or at least about 5%, 8%, 9%, 10%, 15%, 20%, 25%, 50%, 75%, 85%, 95%, or 100% (or ranges spanning and/or including the aforementioned values) of the particles present in the composition (e.g., the aqueous composition). For example, in some embodiments, between about 10% and about 15% of the particles present are unilamellar. In several embodiments, about 12.88% of the particles present are unilamellar.
  • emulsion particles comprise equal to or at least about 5%, 8%, 9%, 10%, 15%, 25%, 50%, 60%, 65%, 70%, 75%, 85%, 95%, or 100% (or ranges spanning and/or including the aforementioned values) of the particles present in the composition (e.g., the aqueous composition).
  • the composition e.g., the aqueous composition.
  • between about 60% to about 75% of the particles present are emulsion particles.
  • about 69.7% of the particles present are emulsion particles.
  • micelle particles comprise equal to or at least about 5%, 8%, 9%, 10%, 15%, 25%, 50%, 60%, 65%, 70%, 75%, 85%, 95%, or 100% (or ranges spanning and/or including the aforementioned values) of the particles present in the composition (e.g., the aqueous composition).
  • liposomes comprise equal to or at least about 5%, 8%, 9%, 10%, 15%, 25%, 50%, 60%, 65%, 70%, 75%, 85%, 95%, or 100% (or ranges spanning and/or including the aforementioned values) of the particles present in the composition (e.g., the aqueous composition).
  • irregular particles comprise equal to or at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 25%, 50%, 75%, 85%, 95%, or 100% (or ranges spanning and/or including the aforementioned values) of the particles present in the composition (e.g., the aqueous composition).
  • the composition e.g., the aqueous composition.
  • between about 1% to about 5% of the particles present are irregular particles.
  • 2.73% are irregular particles.
  • combined lamellar and emulsion particles comprise equal to or at least about 5%, 6%, 7%, 8%, 9%, 10%, 15%, 25%, 50%, 75%, 85%, 95%, or 100% (or ranges spanning and/or including the aforementioned values) of the particles present in the composition (e.g., the aqueous composition).
  • the composition e.g., the aqueous composition.
  • between about 5% to about 6% of the particles present are combined lamellar and emulsion particles.
  • 6.06% of the particles are combined lamellar and emulsion particles.
  • mixed-micelle particles comprise equal to or at least about 5%, 6%, 7%, 8%, 9%, 10%, 15%, 25%, 50%, 75%, 85%, 95%, or 100% (or ranges spanning and/or including the aforementioned values) of the particles present in the composition (e.g., the aqueous composition).
  • the particle compositions can comprise combinations of multilamellar particles, unilamellar particles, emulsion particles, micelle particles, irregular particles, and/or liposomes.
  • the percentages and/or concentrations of particles present in the composition may be purposefully modified.
  • the percentage and/or concentration of the particles present in the composition are tailored to the active compound and/or the liquid comprising the particles. Such tailoring may lead to more homogenization and/or dispersion in the liquid.
  • the tailoring may stabilize dispersion in the liquid.
  • Such tailoring may also tailor to specific densities of the compositions. The densities of the compositions can be matched or different from a liquid that the compositions are contacted by or contained within.
  • the composition is biased towards one type of particle, such as solid particles or liposomes.
  • the composition may be biased by increasing or decreasing the ratio in the composition of lipids that are solid at room temperature to lipids that are liquid at room temperature.
  • Lipids that are liquid at room temperature may comprise MCT (a mixture of capric and caprylic triglycerides, which may have a ratio of c8:cl0 carbon chains of 45:55), captex 1000 (a triglyceride of capric acid).
  • Lipids that are solid at room temperature may comprise solubilizers and/or emollients.
  • Lipids that are solid at room temperature may comprise phosphatidylcholine (such as HSPC) phosphatidylethanolamine, sphingomyelin, triglycerides of oleic acid, and/or triglycerol monooleate.
  • concentration of an oil is adjusted, such as the concentration of a triglyceride, a fatty acid, a diglyceride, or a monoglyceride.
  • the concentration of a sterol such as cholesterol or a plant sterol, is adjusted.
  • the composition is biased towards liposomes by increasing the concentration of lipids that are liquid at room temperature. Biasing the composition may alter characteristics of the composition including density, particle composition, solubility, pharmacokinetic properties, or other characteristics described herein.
  • substituting MCT with a lipid that is a liquid at room temperature and/or increasing the concentration ratio of HSPC to MCT will bias the outcome of the particles more towards liposomes.
  • substituting HSPC with a lipid that is a solid at room temperature will bias the outcome of the particles more towards solid lipid particles.
  • the composition comprises high purity triglycerides, such as oleic acid and/or conjugated linoleics.
  • the composition may be formulated, such as by changing the composition or concentration of lipids, for specific delivery or specific metabolism.
  • the composition may comprise medium chain triglycerides to bias the composition towards phase 1 liver metabolism.
  • the composition is formulated for a specific absorption mechanism, such as lymphatic absorption or liver first pass.
  • the lipid-based particle composition comprises one or more phospholipids.
  • the one or more phospholipids comprises one or more of phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidylinositol phosphate, phosphatidylinositol bisphosphate, and phosphatidylinositol trisphosphate.
  • the phospholipid is phosphatidylcholine.
  • the only phospholipid present is phosphatidylcholine (e.g., the phospholipid lacks phospholipids other than phosphatidylcholine or is substantially free of other phospholipids).
  • the one or more phospholipid components e.g., phosphatidylcholine, and/or others, collectively or individually, are present in the aqueous composition at a concentration of less than or equal to about: 600 mg/ml, 500 mg/ml, 400 mg/ml, 300 mg/ml, 200 mg/ml, 150 mg/ml, 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 10 mg/ml, or ranges including and/or spanning the aforementioned values.
  • the one or more phospholipid(s) are present in the composition at a dry wt % of equal to or less than about: 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, or ranges including and/or spanning the aforementioned values.
  • the one or more phospholipid(s) are present in the composition at a wet wt % of equal to or less than about: 1%, 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 20%, 25%, 30%, 40%, or ranges including and/or spanning the aforementioned values.
  • the composition is aqueous, while in others it has been dried into a powder.
  • the phosphatidylcholine is synthetic, derived from sunflower, soy, egg, or mixtures thereof.
  • the one or more phospholipids (and/or lipids) can be hydrogenated or non-hydrogenated.
  • the phospholipid e.g., phosphatidylcholine
  • the phospholipid may be of high purity.
  • the phosphatidylcholine is H100-3 grade (from Lipoid) and includes over 96.3% phosphatidylcholine (hydrogenated) or over 99% phosphatidylcholine (hydrogenated).
  • the phospholipid e.g., phosphatidylcholine
  • the phospholipid has a purity of greater than or equal to about: 92.5%, 95%, 96%, 96.3%, 98%, 99%, 100%, or ranges including and/or spanning the aforementioned values.
  • the phospholipid e.g., phosphatidylcholine
  • the phospholipid (e.g., phosphatidylcholine) comprises less than or equal to about 8.5%, 5%, 4%, 3.7%, 2%, 1%, or 0.1% (or ranges including and/or spanning the aforementioned values) of any one or more of saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids (C 18), arachidonic acid (ARA) (C 20:4), docosahexaenoic acid DHA (C 22:6), phosphatidic acid, phosphatidylethanolamine, and/or lysophosphatidylcholine by weight.
  • the phosphatidylcholine has less than about 1.1% lysophosphatidylcholine and less than about 2.0% triglycerides by weight.
  • the lipid-based particle composition comprises one or more sterols.
  • the one or more sterols comprises one or more cholesterols, ergosterols, hopanoids, hydroxysteroids, phytosterols (e.g., vegapure), ecdysteroids, and/or steroids.
  • the sterol comprises cholesterol.
  • the sterol is cholesterol.
  • the only sterol present is cholesterol (e.g., the sterol lacks or substantially lacks sterols other than cholesterol).
  • the one or more sterol(s) e.g., cholesterol, and/or other sterols
  • the one or more sterol(s) are present in the aqueous composition at a concentration of less than or equal to about: 100 mg/ml, 50 mg/ml, 40 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 1 mg/ml, or ranges including and/or spanning the aforementioned values.
  • the one or more sterol(s) are present in the composition at a dry wt % of equal to or less than about: 0.25%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 30%, 40%, or ranges including and/or spanning the aforementioned values.
  • the one or more sterol(s) (collectively or individually) are present in the composition at a wet wt % of equal to or less than about: 0.1%, 0.25%, 0.5%, 1%, 2%, 3%, 4%, 5%, 7.5%, 10%, 15%, 20%, or ranges including and/or spanning the aforementioned values.
  • the composition is aqueous, while in others it has been dried into a powder.
  • the cholesterol used in the composition comprises cholesterol from one or more of sheep’s wool, synthetic cholesterol, or semisynthetic cholesterol from plant origin.
  • the sterol (or combination of sterols) has a purity of greater than or equal to about: 92.5%, 95%, 96%, 98%, 99%, 99.9%, 100.0%, or ranges including and/or spanning the aforementioned values.
  • the sterol has a total % impurity content by weight of less than or equal to about: 8.5%, 5%, 4%, 3.7%, 2%, 1%, 0%, or ranges including and/or spanning the aforementioned values.
  • the sterol is cholesterol.
  • the sterol is not cholesterol.
  • the sterol is phytosterol.
  • the lipid-based particle composition comprises a lipid component (e.g., a lipid that is not a phospholipid).
  • the lipid (or mixture of lipids) used in the composition is a liquid at room temperature.
  • the lipid(s) is one in which the therapeutic (e.g., CBD) is soluble.
  • the lipid(s) comprises one or more of a triglyceride(s) and/or one or more oils.
  • the oil may be hemp oil and/or marijuana oil.
  • the lipid (e.g., the triglyceride) comprises one or more medium chain triglycerides (MCTs).
  • MCTs medium chain triglycerides
  • the lipid comprises one or more medium chain triglycerides that can be an ester of glycerol and any one or more medium chain fatty acids.
  • the medium chain triglyceride comprises a fatty acid with an aliphatic tail 6-12 carbons in length (e.g., 6, 7, 8, 9, 10, 11, or 12) or combinations of different chain length fatty acids.
  • the MCT could comprise a tri-ester of glycerol and one fatty acid having an aliphatic chain length of 8, one fatty acid having an aliphatic chain length of 9, and one fatty acid having an aliphatic chain length of 10.
  • the MCT could comprise a tri-ester of glycerol and three fatty acid having an aliphatic chain that is the same length (e.g., each having a length of 8).
  • the medium chain fatty acids of the MCT include one or more of caproic acid, heptanoic acid, octanoic acid, nonanoic acid, capric acid, undecanoic acid, and/or lauric acid, or any combination thereof.
  • the lipid comprises tristearin.
  • the lipid component comprises one or more long chain triglycerides.
  • the long chain triglyceride comprises a fatty acid having a tail that is greater than 12 carbons in length (e.g., greater than or equal to 13, 14, 15, 16, 17, 18, 19, or 20 carbons in length, or ranges including and/or spanning the aforementioned values) and glycerol.
  • the lipid component comprises a short chain triglyceride (SCT).
  • the short chain triglyceride comprises a fatty acid tail less than 6 carbons in length (e.g., less than or equal to 5, 4, 3, 2, 1 carbons in length, or ranges including and/or spanning the aforementioned values).
  • the lipid is a triglyceride that is a tri-ester of fatty acids having aliphatic chain lengths 6 to 20 carbons in length.
  • the composition lacks long chain triglycerides.
  • the lipid comprises one or more of tricaprin, trilaurin, trimyristine, tripalmitin, and tristearin.
  • the lipid is a triglyceride that is a tri-ester of fatty acids having aliphatic chain lengths 1 to 20 carbons in length.
  • the composition lacks long chain triglycerides.
  • the lipid (e.g., that is not a phospholipid) comprises one or more short chain, medium chain, long chain fatty acids, or combinations thereof (e.g., nontriglycerides that are not an ester of glycerol).
  • the short chain fatty acid comprises a fatty acid tail less than 6 carbons in length (e.g., less than or equal to 5, 4, 3, 2, 1 carbons in length, or ranges including and/or spanning the aforementioned values).
  • the medium chain fatty acid comprises an aliphatic tail 6-12 carbons in length (e.g., 6, 7, 8, 9, 10, 11, or 12).
  • the long chain fatty acid comprises a tail that is greater than 12 carbons in length (e.g., greater than or equal to 13, 14, 15, 16, 17, 18, 19, or 20 carbons in length, or ranges including and/or spanning the aforementioned values).
  • the lipid comprises one or more different chain length fatty acids (short chain, medium chain, long chain, or combinations thereof). In several embodiments, the lipid comprises one or more different chain length fatty acids (short chain, medium chain, long chain, or combinations thereof) and one or more different chain length triglycerides (as disclosed elsewhere herein).
  • the one or more lipid(s) are present in the aqueous composition at a concentration of less than or equal to about: 400 mg/ml, 300 mg/ml, 200 mg/ml, 150 mg/ml, 100 mg/ml, 93 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 10 mg/ml, 5 mg/ml, 1 mg/ml, or no lipid, or ranges including and/or spanning the aforementioned values.
  • 400 mg/ml 300 mg/ml, 200 mg/ml, 150 mg/ml, 100 mg/ml, 93 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, 10 mg/ml, 5 mg/ml, 1 mg/ml, or no lipid, or ranges including and/or spanning the aforementioned values.
  • the one or more lipids are present in the composition (collectively or individually) at a dry wt % of equal to or less than about: 0%, 1%, 2.5%, 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, or ranges including and/or spanning the aforementioned values.
  • the one or more lipids are present in the composition at a wet wt % of equal to or less than about: 0%, 1%, 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 20%, 30%, 40%, or ranges including and/or spanning the aforementioned values.
  • the composition is aqueous, while in others it has been dried into a powder.
  • the lipid has a purity of greater than or equal to about: 92.5%, 95%, 96%, 98%, 99%, 99.9%, or ranges including and/or spanning the aforementioned values.
  • the lipid has a total % impurity content by weight of less than or equal to about: 8.5%, 5%, 4%, 3.7%, 2%, 1%, 0%, or ranges including and/or spanning the aforementioned values.
  • the lipid that is not a phospholipid is not an MCT or LCT but is an MCT-substitute.
  • the MCT-substitute lipid is selected from one or more of oleic acid, capric acid, caprylic acid, and triglycerides of such (Captex 8000, Captex GTO, Captex 1000), glycerol monooleate, glycerol monostearate (GeleolTM Mono and Diglyceride NF), omega-3 fatty acids (a-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), Tonalin, Pronova Pure® 46:38, free fatty acid Tonalin FFA 80), conjugated linoleic acid, alpha glycerylphosphorylcholine (alpha GPC), palmitoylethanolamide (PEA), cetyl alcohol, or emulsifying wax.
  • oleic acid e.g., the nonphospholipid lipid
  • capric acid e.g., the nonphospholipid lipid
  • caprylic acid
  • the one or more MCT-substitute lipids are present in the lipid-based particle composition (collectively or individually) at a dry wt % of equal to or less than about: 0%, 0.1% 0.5%, 1.0%, 2.5%, 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 80% or ranges including and/or spanning the aforementioned values.
  • the one or more MCT-substitute lipids are present in the composition at a wet wt % of equal to or less than about: 0%, 0.1%, 0.5%, 1.0% 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 20%, 30%, 40%, 60% or ranges including and/or spanning the aforementioned values.
  • the MCT-substitute lipid has a purity of greater than or equal to about: 70%, 80%, 85%, 92.5%, 95%, 96%, 98%, 99%, 99.9%, 100%, or ranges including and/or spanning the aforementioned values.
  • the MCT-substitute lipid has a total % impurity content by weight of less than or equal to about: 8.5%, 5%, 4%, 3.7%, 2%, 1%, 0%, or ranges including and/or spanning the aforementioned values.
  • the non-phospholipid lipid is an MCT.
  • the lipid-based particle composition comprises a preservative.
  • the preservative includes one or more benzoates (such as sodium benzoate or potassium benzoate), nitrites (such as sodium nitrite), sulfites (such as sulfur dioxide, sodium or potassium sulphite, bisulphite or metabisulphite), sorbates (such as sodium sorbate, potassium sorbate), ethylenediaminetetraacetic acid (EDTA) (and/or the disodium salt thereof), polyphosphates, organic acids (e.g., citric, succinic, malic, tartaric, benzoic, lactic and propionic acids), and/or antioxidants (e.g., vitamins such as vitamin E and/or vitamin C, butylated hydroxy toluene).
  • benzoates such as sodium benzoate or potassium benzoate
  • nitrites such as sodium nitrite
  • sulfites such as sulfur dioxide, sodium or potassium sulphite, bisulphit
  • the one or more preservatives are present in the aqueous composition at a concentration of less than or equal to about: 10 mg/ml, 5 mg/ml, 1 mg/ml, 0.85 mg/ml, 0.5 mg/ml, 0.1 mg/ml, or ranges including and/or spanning the aforementioned values.
  • the one or more preservatives are present in the composition at a dry wt % of equal to or at less than about: 0.01%, 0.1%, 0.25%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values.
  • the one or more preservatives are present in the composition at a wet wt % of equal to or less than about: 0.001%, 0.01%, 0.025%, 0.05%, 0.1%, 0.5%, 0.75%, 1.0%, 1.5%, 2.0%, 2.5%, 5%, or ranges including and/or spanning the aforementioned values.
  • the composition is aqueous, while in others it has been dried into a powder.
  • the aqueous composition comprises one or more of malic acid at about 0.85 mg/ml, citric acid at about 0.85 mg/ml, potassium sorbate at about 1 mg/ml, and sodium benzoate at about 1 mg/ml.
  • the preservatives inhibit or prevent growth of mold, bacteria, and fungus.
  • Vitamin E is added at 0.5 mg/ml to act as an antioxidant in the oil phase.
  • the preservative concentrations may be changed depending on the flavored oil used.
  • the lipid-based particle composition comprises one or more flavoring agents.
  • the one or more flavoring agent(s), collectively or individually, are present in the aqueous composition at a concentration of less than or equal to about: 10 mg/ml, 5 mg/ml, 1.5 mg/ml, 1.2 mg/ml, 1 mg/ml, 0.9 mg/ml, 0.5 mg/ml, 0.1 mg/ml, or ranges including and/or spanning the aforementioned values.
  • the one or more flavoring agent(s) are present in the composition at a dry wt % of equal to or less than about: 0.01%, 0.1%, 0.25%, 0.5%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values.
  • the one or more flavoring agents are present in the composition at a wet wt % of equal to or less than about: 0.001%, 0.01%, 0.025%, 0.05%, 0.1%, 0.5%, 0.75%, 1.0%, 1.5%, 2.0%, 2.5%, 5.0%, 10%, or ranges including and/or spanning the aforementioned values.
  • the composition is aqueous, while in others it has been dried into a powder.
  • the one or more flavoring agents of the composition comprise monk fruit extract (e.g., MonkGold50), stevia, peppermint oil, lemon oil, vanilla, or the like, or combinations thereof.
  • the composition contains MonkGold50 at 0.9 mg/ml and flavored oils as flavoring. Examples of flavored oils are peppermint and lemon at 1.2 mg/ml. Chemicals that are not oil may also be used for flavor, for example, such as dry powders that replicate a flavor such as vanilla.
  • the lipid-based particle composition is aqueous while in other embodiments the composition may be provided as a dry or substantially dry solid (e.g., having a water content in weight % of less than or equal to 21%, 20%, 15%, 10%, 5%, 2%, 1%, 0.5%, or ranges including and/or spanning the aforementioned values).
  • water may be present at a wet weight percent of equal to or less than about: 22%, 30%, 40%, 50%, 60%, 70%, 75%, 77%, 80%, 85%, 90%, 95%, 97.5%, 99%, or ranges including and/or spanning the aforementioned values.
  • the lipid-based particle composition comprises one or more carbohydrates (and/or a carbohydrate source).
  • the carbohydrate source is selected from the group consisting of trehalose, sucrose, dextrose, glucose, isomaltulose, tagatose, arabinose, maltose, fructose, dextrin, lactose, maltose, fucose, galactose, inositol, maltodextrin, maltol, mannose, muscovado, ribose, rhamnose, saccharose, sucralose, xylose, lecithin, avocado fiber, acacia fiber, psyllium fiber, betaglucan, guar gum, xanthan gum, pectin, chitin, cellulose, hemicellulose, sodium alginate, potassium alginate, ammonium alginate, calcium alginate, ammonium alginate, propylene
  • the one or more carbohydrates are present in the aqueous composition at a concentration of less than or equal to about: 100 mg/ml, 90 mg/ml, 80 mg/ml, 70 mg/ml, 60 mg/ml, 50 mg/ml, 40 mg/ml, 30 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 1.5 mg/ml, 1.2 mg/ml, 1 mg/ml, 0.9 mg/ml, 0.5 mg/ml, 0.1 mg/ml, 0.01 mg/ml, 0.001 mg/ml or ranges including and/or spanning the aforementioned values.
  • the one or more carbohydrates are present in the composition at a dry wt % of equal to or less than about: 0.001%, 0.01%, 0.1%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 35%, 50%, 60%, 70%, 80%, 90%, 95% or ranges including and/or spanning the aforementioned values.
  • the one or more carbohydrates are present in the composition at a wet wt % of equal to or less than about: 0.001%, 0.01%, 0.1%, 0.1%, 0.5%, 0.75%, 1.0%, 1.5%, 2.0%, 2.5%, 5.0%, 10%, 15%, 20%, 30%, 40%, 50%, or ranges including and/or spanning the aforementioned values.
  • the composition is aqueous, while in others it has been dried into a powder.
  • the one or more carbohydrates surprisingly, stabilize the lipid composition when in powdered form (e.g., dry or substantially dry form).
  • the one or more carbohydrates surprisingly help the lipid composition to return to particle form (e.g., nano or microparticle form) when reconstituted.
  • the lipid-based particle composition comprises one or more one or more other additives, such as amino acids, polyethylene glycols, etc.
  • the one or more additives (or carbohydrate source(s)), collectively or individually, are present in the aqueous composition at a concentration of less than or equal to about: 100 mg/ml, 90 mg/ml, 80 mg/ml, 70 mg/ml, 60 mg/ml, 50 mg/ml, 40 mg/ml, 30 mg/ml, 20 mg/ml, 10 mg/ml, 5 mg/ml, 1.5 mg/ml, 1.2 mg/ml, 1 mg/ml, 0.9 mg/ml, 0.5 mg/ml, 0.1 mg/ml, 0.01 mg/ml, 0.001 mg/ml or ranges including and/or spanning the aforementioned values.
  • the one or more additives are present in the composition at a dry wt % of equal to or less than about: 0.001%, 0.01%, 0.1%, 1%, 5%, 7.5%, 10%, 15%, 20%, 25%, 35%, 50%, 60%, 70%, 80%, 90%, 95% or ranges including and/or spanning the aforementioned values.
  • the one or more additives are present in the composition at a wet wt % of equal to or less than about: 0.001%, 0.01%, 0.1%, 0.1%, 0.5%, 0.75%, 1.0%, 1.5%, 2.0%, 2.5%, 5.0%, 10%, 15%, 20%, 30%, 40%, 50%, or ranges including and/or spanning the aforementioned values.
  • the composition is aqueous, while in others it has been dried into a powder.
  • the one or more additives surprisingly, stabilize the lipid composition when in powdered form (e.g., dry or substantially dry form).
  • the one or more additives surprisingly help the lipid composition to return to particle form (e.g., nano or microparticle form) when reconstituted.
  • the aqueous lipid-based particle composition comprises phosphatidylcholine in a range from about 8% to about 12%, MCT in a range from about 8% to about 12%, one or more therapeutic agents (e.g., CBD and/or others) in a range from about 1% to about 5%, cholesterol in a range from about 0.5% to about 4%, and water in a range from about 60% to about 90%.
  • phosphatidylcholine in a range from about 8% to about 12%
  • MCT in a range from about 8% to about 12%
  • one or more therapeutic agents e.g., CBD and/or others
  • the aqueous composition further comprises one or more of vitamin E in a range from about 0.01% to about 1.0%, malic acid in a range from about 0.01% to about 1.0%, citric acid in a range from about 0.01% to about 1.0%, potassium sorbate in a range from about 0.01% to about 2.0%, sodium benzoate in a range from about 0.01% to about 2.0%, and/or monk fruit extract in a range from about 0.01% to about 2.0%.
  • the composition is aqueous and includes one or more therapeutic agents (e.g., CBD and/or others) at about 20 mg/ml, phosphatidylcholine at about 100 mg/ml, cholesterol at about 10 mg/ml, and MCT at about 93 mg/ml.
  • one or more therapeutic agents e.g., CBD and/or others
  • phosphatidylcholine at about 100 mg/ml
  • cholesterol at about 10 mg/ml
  • MCT at about 93 mg/ml.
  • the aqueous lipid-based particle composition comprises phosphatidylcholine in a range from about 9% to about 11%, MCT in a range from about 8% to about 10%, one or more therapeutic agents (e.g., CBD and/or others) in a range from about 1% to about 3%, cholesterol in a range from about 0.5% to about 2%, and water in a range from about 70% to about 80%.
  • the aqueous composition further comprises one or more of vitamin E in a range from about 0.01% to about 1.0%, malic acid in a range from about 0.01% to about 1.0%, citric acid in a range from about 0.01% to about 1.0%, potassium sorbate in a range from about 0.01% to about 2.0%, sodium benzoate in a range from about 0.01% to about 2.0%, and/or monk fruit extract in a range from about 0.01% to about 2.0%.
  • the lipid-based particle composition comprises (in dry wt %) phosphatidylcholine in a range from about 40% to about 50%, MCT in a range from about 35% to about 45%, one or more therapeutic agents (e.g., CBD and/or others) in a range from about 5% to about 25%, and cholesterol in a range from about 2.5% to about 10%.
  • phosphatidylcholine in a range from about 40% to about 50%
  • MCT in a range from about 35% to about 45%
  • one or more therapeutic agents e.g., CBD and/or others
  • cholesterol in a range from about 2.5% to about 10%.
  • the composition further comprises (in dry weight) one or more of vitamin E in a range from about 0.01% to about 2.0%, malic acid in a range from about 0.01% to about 2.0%, citric acid in a range from about 0.01% to about 2.0%, potassium sorbate in a range from about 0.01% to about 2.0%, sodium benzoate in a range from about 0.01% to about 2.0%, and/or monk fruit extract in a range from about 0.01% to about 2.0%.
  • vitamin E in a range from about 0.01% to about 2.0%
  • malic acid in a range from about 0.01% to about 2.0%
  • citric acid in a range from about 0.01% to about 2.0%
  • potassium sorbate in a range from about 0.01% to about 2.0%
  • sodium benzoate in a range from about 0.01% to about 2.0%
  • monk fruit extract in a range from about 0.01% to about 2.0%.
  • the lipid-based particle composition comprises (in dry wt %) phosphatidylcholine in a range from about 42% to about 46%, MCT in a range from about 39% to about 43%, one or more therapeutic agents (e.g., CBD and/or others) in a range from about 5% to about 15%, and cholesterol in a range from about 2.5% to about 7%.
  • phosphatidylcholine in a range from about 42% to about 46%
  • MCT in a range from about 39% to about 43%
  • one or more therapeutic agents e.g., CBD and/or others
  • cholesterol in a range from about 2.5% to about 7%.
  • the composition further comprises (in dry weight) one or more of vitamin E in a range from about 0.01% to about 2.0%, malic acid in a range from about 0.01% to about 2.0%, citric acid in a range from about 0.01% to about 2.0%, potassium sorbate in a range from about 0.01% to about 2.0%, sodium benzoate in a range from about 0.01% to about 2.0%, and/or monk fruit extract in a range from about 0.01% to about 2.0%.
  • the composition can be varied such that the different ratios of the components yield a nanoparticle containing one or more therapeutic agents (e.g., CBD and/or others) that are stable.
  • a solid lipid nanoparticle of the lipid-based particle compositions comprises a lipid core matrix.
  • the lipid core matrix is solid.
  • the solid lipid comprises one or more ingredients as disclosed elsewhere herein.
  • the core of the solid lipid comprises one or more triglycerides (e.g., tristearin), diglycerides (e.g. glycerol behenate), monoglycerides (e.g. glycerol mono stearate), fatty acids (e.g. stearic acid), steroids (e.g. cholesterol), and waxes (e.g. cetyl palmitate).
  • emulsifiers can be used to stabilize the lipid dispersion (with respect to charge and molecular weight).
  • the core ingredients and/or the emulsifiers are present in the composition (collectively or individually) at a dry wt % of equal to or less than about: 0.5%, 1.0%, 2.5%, 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 80% or ranges including and/or spanning the aforementioned values.
  • the core ingredients and/or the emulsifiers are present in the composition at a wet wt % of equal to or less than about: 0.5%, 1.0% 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 20%, 30%, 40%, 60% or ranges including and/or spanning the aforementioned values.
  • the core ingredients and/or the emulsifiers have a purity of greater than or equal to about: 70%, 80%, 85%, 92.5%, 95%, 96%, 98%, 99%, 99.9%, 100%, or ranges including and/or spanning the aforementioned values.
  • the lipid-based particle composition (e.g., when in water or dried) comprises multilamellar nanoparticle vesicles, unilamellar nanoparticle vesicles, multivesicular nanoparticles, emulsion particles, irregular particles with lamellar structures and bridges, partial emulsion particles, combined lamellar and emulsion particles, and/or combinations thereof.
  • the composition is characterized by having multiple types of particles (e.g., lamellar, emulsion, irregular, etc.). In other embodiments, a majority of the particles present are emulsion particles.
  • a majority of the particles present are lamellar (multilamellar and/or unilamellar). In other embodiments, a majority of the particles present are irregular particles. In still other embodiments, a minority of the particles present are emulsion particles. In several embodiments, a minority of the particles present are lamellar (multilamellar and/or unilamellar). In other embodiments, a minority of the particles present are irregular particles.
  • the particles present in the composition are multilamellar nanoparticle vesicles.
  • the particles present in the composition are multilamellar nanoparticle vesicles.
  • the particles present in the composition are multilamellar nanoparticle vesicles.
  • between about 5% and about 10% of the particles present are multilamellar.
  • about 8.6% of the particles present are multilamellar.
  • the particles present in the composition are unilamellar nanoparticle vesicles.
  • the particles present in the composition are unilamellar nanoparticle vesicles.
  • the particles present in the composition are unilamellar nanoparticle vesicles.
  • between about 10% and about 15% of the particles present are unilamellar.
  • about 12.88% of the particles present are unilamellar.
  • the particles present in the composition are emulsion particles.
  • the particles present in the composition are emulsion particles.
  • the particles present in the composition are emulsion particles.
  • emulsion particles are emulsion particles.
  • between about 60% to about 75% of the particles present are emulsion particles.
  • about 69.7% of the particles present are emulsion particles.
  • the particles present in the composition are irregular particles (e.g., with lamellar structures and/or bridges).
  • irregular particles e.g., with lamellar structures and/or bridges.
  • of the particles present in the composition are irregular particles.
  • between about 1% to about 5% of the particles present are irregular particles.
  • 2.73% are irregular particles.
  • the particles present in the composition are combined lamellar and emulsion particles.
  • the particles present in the composition are combined lamellar and emulsion particles.
  • lamellar and emulsion particles are combined lamellar and emulsion particles.
  • between about 5% to about 6% of the particles present are combined lamellar and emulsion particles.
  • 6.06% of the particles are combined lamellar and emulsion particles.
  • the composition (e.g., the aqueous composition) comprises between 60% and 80% emulsion particles. In several embodiments, the composition (e.g., the aqueous composition) comprises between 7.5% and 20% small unilamellar vesicles. In several embodiments, the composition (e.g., the aqueous composition) comprises between 5% and 15% multilamellar vesicles. In several embodiments, the composition (e.g., the aqueous composition) comprises between 3% and 10% combined lamellar and emulsion particles. In several embodiments, the composition (e.g., the aqueous composition) comprises between 1% and 6% irregular particles.
  • the composition (e.g., the aqueous composition) comprises between 65% and 75% emulsion particles. In several embodiments, the composition (e.g., the aqueous composition) comprises between 10% and 15% small unilamellar vesicles. In several embodiments, the composition (e.g., the aqueous composition) comprises between 5% and 12% multilamellar vesicles. In several embodiments, the composition (e.g., the aqueous composition) comprises between 4% and 8% combined lamellar and emulsion particles. In several embodiments, the composition (e.g., the aqueous composition) comprises between 1% and 4% irregular particles.
  • the composition (e.g., the aqueous composition) comprises between 60% and 80% emulsion particles, between 7.5% and 20% small unilamellar vesicles, between 5% and 15% multilamellar vesicles, between 3% and 10% combined lamellar and emulsion particles, and between 1% and 6% irregular particles.
  • the composition (e.g., the aqueous composition) comprises between 65% and 75% emulsion particles, between 10% and 15% small unilamellar vesicles, between 5% and 12% multilamellar vesicles, between 4% and 8% combined lamellar and emulsion particles, and between 1% and 4% irregular particles.
  • the composition (e.g., the aqueous composition) comprises 69.7% emulsion particles, 12.88% small unilamellar vesicles, 8.64% multilamellar vesicles, 6.06% combined lamellar and emulsion particles, and 2.73% irregular particles.
  • solutions of particles are composed of non-lipid ingredients, such as polymers.
  • solutions are cannabinoids, mushrooms, mushroom extracts or powders, kratom extracts or powders, kanna extracts or powders, kava extracts or powders are prepared without one or more of phospholipids, sterols, lipid components (e.g., those other than phospholipids), preservatives, flavoring agents, and/or carbohydrates and other additives.
  • an aqueous lipid-based composition as disclosed herein has a viscosity (in centipoise (cP)) of equal to or less than about: 1.0, 1.05, 1.1, 1.2, 1.5, 2.0, 5.0, 10.0, 20, 30, 50, 100, or ranges including and/or spanning the aforementioned values.
  • cP centipoise
  • the lipid-based particle composition has a viscosity (in centipoise (cP)) of equal to or less than about: 1.0, 1.05, 1.1, 1.2, 1.5, 2.0, 5.0, 10.0, 20, 30, 50, 100, or ranges including and/or spanning the aforementioned values.
  • cP centipoise
  • the lipid-based particle composition has a viscosity (in cP) of equal to or less than about: 1.0, 1.05, 1.1, 1.2, 1.5, 2.0, 5.0, 10.0, 20, 30, 50, 100, or ranges including and/or spanning the aforementioned values.
  • the viscosity of the CBD lipid nanoparticle aqueous solution is equal to or less than 5.0 Cp.
  • the liposomes and/or a liquid (e.g., aqueous) composition comprising the nanoparticles as disclosed herein are lyophilized.
  • one or more lyoprotectant agents may be added.
  • an individual lyoprotectant agent may be present at a dry wt % equal to or less than the dry weight of the lipophilic ingredients.
  • the lyoprotectant agent(s) may be present at a dry wt % equal to or less than about: 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, or ranges including and/or spanning the aforementioned values.
  • the lyoprotectant agent(s) may be present at a wet wt % of equal to or less than about: 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 20%, 30%, or ranges including and/or spanning the aforementioned values.
  • the lyoprotectant is selected from the group consisting of lactose, dextrose, trehalose, arginine, glycine, histidine, and/or combinations thereof.
  • compositions comprising nanoparticles and/or liposomes.
  • the composition is prepared by forming a lipid-in-oil emulsion.
  • an oil-in-water emulsion can be prepared without the use of organic solvents as shown in Figure 1 (e.g., in an organic solvent-free method).
  • solid ingredients 101 are added and dissolved into liquid ingredients 102.
  • one or more of the sterol (e.g., cholesterol) and/or therapeutic agent(s) can be dissolved in lipid oil (e.g., a medium chain triglyceride) and/or vitamin E.
  • lipid oil e.g., a medium chain triglyceride
  • the phospholipid e.g., phosphatidylcholine
  • the phospholipid can be added with mixing.
  • the addition of water 103 e.g., having a temperature of equal to or at least about: 10°C, 20°C, 30°C, 40°C, 50°C, 60°C, 80°C, or ranges including and/or spanning the aforementioned values
  • additional mixing 104 achieves an oil-in-water emulsion 105.
  • the oil-in-water emulsion is then subject to high-shear mixing to form nanoparticles (e.g., therapeutic agent and/or CBD liposomes).
  • high-shear mixing 106 is performed using a high shear dispersion unit or an in-line mixer can be used to prepare the emulsions.
  • the particles can be made by solvent evaporation and/or solvent precipitation.
  • the lipid-in-oil emulsion is formed by dissolving ingredients 201, such as, one or more of a phospholipid (e.g., phosphatidylcholine), a sterol (e.g., cholesterol), one or more therapeutic agents (e.g., phytocannabinoid, CBD, etc.), a lipid (e.g., a medium chain triglyceride), and/or a preservative (e.g., vitamin E) in a solvent 202.
  • the solvent can include one or more organic solvents, including but not limited to, ethanol, chloroform, and/or ethyl acetate.
  • the solvents are class II solvents, class III solvents (e.g., at least class II and/or class III by the ICH Q3C standard), or mixtures thereof.
  • the solution of ingredients and solvent is dried 203.
  • the ingredients are provided as lipids and or liposomes as a thin film.
  • the solvent is removed from the composition by subjecting the solution to heat under vacuum to promote evaporation.
  • the film may further be dried under nitrogen gas.
  • the lipid film is hydrated 205 with warm aqueous solution to form an oil-in-water emulsion.
  • high- shear mixing is performed 206 using a high shear dispersion unit or an in-line mixer can be used to prepare the emulsions.
  • the lipid-in-water emulsion is subject to high pressure homogenization using a microfluidizer.
  • high sheer mixing can be used to reduce the particle size.
  • the oil-in-water emulsion is processed to a nanoparticle (e.g., about 20 to about 500 nm, etc.) using the microfluidizer or other high sheer processes.
  • the oil-in-water emulsion is processed to a nanoparticle having a size from about 80 nm to 180 nm in diameter or about 100 nm to about 150 nm in diameter.
  • the lipid-in-water emulsion is passed through the microfluidizer a plurality of times (e.g., equal to or at least 1 time, 2 times, 3 times, 4 times, 5 times, 10 times, or ranges including and/or spanning the aforementioned values).
  • the emulsion is passed through the microfluidizer at a pressure of equal to or less than about: 5,000 PSI, 15,000 PSI, 20,000 PSI, 25,000 PSI, 30,000 PSI, or ranges including and/or spanning the aforementioned values.
  • the emulsion is passed through the microfluidizer at a temperature of equal to or at least about: 30°C, 40°C, 50°C, 65°C, 80°C, or ranges including and/or spanning the aforementioned values.
  • the emulsion is passed through the microfluidizer at least about room temperature (e.g., about 20°C or about 25°C) and/or without any heating and/or temperature control.
  • the emulsion is passed through the microfluidizer at a temperature of equal to or less than about 80°C.
  • the microfluidizer includes an interaction chamber consisting of 75 pm to 200 pm pore sizes and the emulsion is passed through this chamber.
  • the pore size of the microfluidizer are less than or equal to about: 75 pm, 100 pm, 150 pm, 200 pm, 250 pm, 300 pm, or ranges including and/or spanning the aforementioned values.
  • the nanoparticle composition is prepared by high shear mixing, sonication, or extrusion.
  • the lipid-based particle composition is characterized by an ability to pass through a 0.2 pm filter while preserving the nanoparticle structure (e.g., a change in average nanoparticle size of no greater than 10 nm, 20 nm, or 30 nm).
  • a change in average nanoparticle size of no greater than 10 nm, 20 nm, or 30 nm e.g., a change in average nanoparticle size of no greater than 10 nm, 20 nm, or 30 nm.
  • after passage through a 0.2 pm there is a change in average diameter of the particles of equal to or at less than about: 1%, 5%, 10%, 20%, or ranges including and/or spanning the aforementioned values.
  • after passage through a 0.2 pm there is a change in PDI of the particles of equal to or at less than about: 1%, 5%, 10%, 20%, or ranges including and/or spanning the aforementioned values.
  • the lipid-based particle composition is composed of highly pure ingredients. These may include GMP manufactured CBD isolate or other therapeutic agents. In several embodiments, the CBD or other therapeutic agents are triple checked for potency and purity, and has negligible concentrations of THC or other impurities. In several embodiments, the composition (and/or one or more ingredients constituting the compositions) is manufactured with high purity, multicompendial ingredients to be at the same standards as pharmaceutical products. In several embodiments, the composition is manufactured using pharmaceutical equipment and documentation to ensure the product is of high quality and consistent from batch to batch.
  • the therapeutic nanoparticle composition imparts solubility to hydrophobic therapeutic agents (e.g., CBD, other phytocannabinoids, etc.) in a delivery system that is easily dispersible in aqueous solutions.
  • hydrophobic therapeutic agents e.g., CBD, other phytocannabinoids, etc.
  • CBD oils do not disperse well in aqueous solutions and have poor oral absorption.
  • CBD particle formulations made using methods other than those disclosed herein have inconsistent particle size and may not be stable with storage over time.
  • the nanoparticle delivery systems comprising e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing
  • the method of manufacture of the compositions avoids the introduction of contaminants (such as metal contamination).
  • over 50%, 75%, 95% (or ranges spanning and or including the aforementioned values) of the nanoparticles prepared by the methods disclosed herein have a particle size of between about 20 to about 500 nm (as measured by zeta sizing (e.g., refractive index).
  • the nanoparticles prepared by the methods disclosed herein have a particle size of between about 50 nm to about 200 nm (as measured by zeta sizing (e.g., refractive index). In several embodiments, over 50%, 75%, 95% (or ranges spanning and or including the aforementioned values) of the nanoparticles prepared by the methods disclosed herein have a particle size of between about 90 nm to about 150 nm (as measured by zeta sizing (e.g., refractive index). In several embodiments, this consistency in size allows predictable delivery to subjects.
  • the D90 particle size measurement varies between 150 and 500 nm.
  • the lipid-based delivery system described herein offers protection to therapeutic agents (e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing) against degradation in an aqueous environment for long-term storage.
  • therapeutic agents e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing
  • the composition is well characterized to ensure a consistent product from batch to batch and with long-term stability.
  • the product stability is routinely tested for appearance, particle size and distribution, zeta potential, residual solvents, heavy metals, therapeutic agent (e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing) concentration, and microbial testing and the values measured using these test methods varies (over a period of at least about 1 month or about 6 months at 25°C with 60% relative humidity) by less than or equal to about: 1%, 5%, 10%, 20%, 30%, or ranges including and/or spanning the aforementioned values.
  • therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing
  • the particle size and/or PDI varies over a period of at least about 1 month or about 6 months (at 25°C with 60% relative humidity) by less than or equal to about: 1%, 5%, 10%, 20%, 30%, or ranges including and/or spanning the aforementioned values.
  • PDI and size can be measured using conventional techniques disclosed herein.
  • the therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing concentration varies over a period of at least about 1 month or about 6 months (at 25 °C with 60% relative humidity) by less than or equal to about: 1%, 5%, 10%, 15%, or ranges including and/or spanning the aforementioned values.
  • PDI and size can be measured using conventional techniques disclosed herein.
  • the formulations and/or compositions disclosed herein are stable during sterilization.
  • the sterilization may include one or more of ozonation, UV treatment, and/or heat treatment.
  • the particle size and/or PDI after sterilization varies by less than or equal to about: 1%, 5%, 10%, 20%, 30%, or ranges including and/or spanning the aforementioned values.
  • the therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing
  • concentration after sterilization varies (e.g., drops) by less than or equal to about: 1%, 5%, 10%, 15%, or ranges including and/or spanning the aforementioned values.
  • the lipid-based particle compositions (including after stabilization) disclosed herein have a shelf life of equal to or greater than 6 months, 12 months, 14 months, 16 months, 18 months, 19 months, or ranges including and/or spanning the aforementioned values.
  • the shelf life can be determined as the period of time in which there is 95% confidence that at least 50% of the response (therapeutic agent(s) concentration or particle size) is within the specification limit. This refers to a 95% confidence interval and when linear regression predicts that at least 50% of the response is within the set specification limit.
  • the dashed line on the stability plot is the 95% confidence interval and the solid line is the linear regression.
  • the dots are the responses.
  • the response variable is either Z-average particle size or therapeutic agent (e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing) concentration in Figures 3 and 4.
  • the particle size specification is 100 to 200 nm
  • the therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing concentration specification is 18 to 22 mg / mL.
  • the lipid-based particle composition contains preservatives to protect against bacteria, mold, and fungal growth.
  • the product specification is no more than 100 cfu/gram.
  • the composition has equal to or not more than: 50 cfu/gram, 10 cfu/gram, 5 cfu/gram, 1 cfu/gram, 0.1 cfu/gram, or ranges including and/or spanning the aforementioned values.
  • the composition has equal to or not more than: 100 cfu/gram, 50 cfu/gram, 25 cfu/gram, 10 cfu/gram, 5 cfu/gram, 1 cfu/gram, 0.1 cfu/gram, or ranges including and/or spanning the aforementioned values.
  • the composition has a log reduction for the bacteria of equal to or greater than: 1, 2, 3, 4, 5, 10, or ranges including and/or spanning the aforementioned values.
  • the lipid-based particle composition ingredients provided herein provides a proper ratio and/or combination of ingredients that allow it to maintain stability and efficacy as disclosed elsewhere herein (e.g., during long term storage for example).
  • the individual particles within the disclosed lipid-based particle compositions may not settle or sediment appreciably.
  • an appreciable amount of the composition e.g., as viewed by the naked eye
  • the composition does not settle and/or separate from an aqueous liquid upon standing.
  • the composition does not appreciably settle or separate from an aqueous liquid upon standing for equal to or at least about 1 day, at least about 1 month, about 3 months, about 6 months, about 9 months, about 1 year, or ranges including and/or spanning the aforementioned values.
  • the composition upon standing, the composition remains dispersed in an aqueous liquid for at least about 1 day, at least about 1 month, about 3 months, about 6 months, about 9 months, about 1 year, or ranges including and/or spanning the aforementioned values.
  • the homogeneity of the disclosed compositions changes by equal to or less than about: 0.5%, 1%, 5%, 7.5%, 10%, or 15% (or ranges including and/or spanning the aforementioned values) after a period of one week or one month. In this case, homogeneity is observed through images by SEM or cryo-SEM (e.g., the average size of the particles and/or the particle types).
  • the composition remains dispersed in an aqueous liquid and does not appreciably settle or separate from an aqueous liquid after at least about: 1 minute, 5 minutes, 30 minutes, or an hour in a centrifuge at a centripetal acceleration of at least about 100 m/s, at least about 1000 m/s, or at least about 10,000 m/s. In several embodiments, the composition remains dispersed in an aqueous liquid and does not appreciably settle or separate from an aqueous liquid after at least about: 1 minute, 5 minutes, 30 minutes, or an hour in a centrifuge at a centrifuge speed of 5000 RPM, 10,000 RPM, or 15,000 RPM.
  • the nanoparticle delivery system aids in absorption of the therapeutic agent (e.g., cannabinoids, such as CBD, noncannabinoids, and/or combinations of any of the foregoing) molecule when orally ingested.
  • the compositions disclosed herein allow the therapeutic agent (e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing) to be delivered to and/or absorbed through the gut.
  • some embodiments pertain to the use of the lipid-based nanodelivery system to protect the therapeutic agent (e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing) from degradation and/or precipitation in the aqueous solution it is stored in (e.g., in an aqueous composition for administration to a subject).
  • the therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing
  • use of the delivery systems disclosed herein result in improved bioavailability and/or absorption rate.
  • the Cmax of a therapeutic is increased using a disclosed embodiment
  • the Tmax of is decreased using an embodiment as disclosed herein
  • the AUC is increased using a disclosed embodiment.
  • the pharmacokinetic outcomes disclosed elsewhere herein can be achieved using aqueous lipid-based particle compositions or powdered lipid-based particle compositions (e.g., where the powder is supplied by itself, in a gel capsule, as an additive to food, etc.).
  • the Cmax of the therapeutic agent or ingredient is increased using the disclosed embodiments relative to other delivery vehicles (e.g., after administration to a subject).
  • the Cmax is increased relative to the therapeutic agent or ingredients (e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing) alone or comparator embodiments (e.g., oil-based products) by equal to or at least about: 15%, 20%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values.
  • the therapeutic agent or ingredients e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • comparator embodiments e.g., oil-based products
  • the therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • Cmax is increased (relative to a comparator oil-based product) by equal to or at least about: 5%, 10%, 20%, 30%, 50%, 100%, or ranges including and/or spanning the aforementioned values.
  • the therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • Cmax is increased (relative to a comparator oil-based product) by equal to or at least about: 10 ng/mL, 20 ng/mL, 30 ng/mL, 40 ng/mL, 50 ng/mL, 60 ng/mL, 70 ng/mL, 80 ng/mL, 90 ng/mL, or ranges including and/or spanning the aforementioned values.
  • the Cmax of CBD is equal to or at least about: 0.5 pg/L, 1 pg/L, 2 pg/L, 3 pg/L, 4 pg/L, 5 pg/L, 6 pg/L, or ranges including and/or spanning the aforementioned values.
  • the Cmax of CBD is equal to or at least about: 40 ng/mL, 50 ng/mL, 60 ng/mL, 70 ng/mL, 80 ng/mL, 90 ng/mL, 100 ng/mL, 150 ng/mL, 200 ng/mL, or ranges including and/or spanning the aforementioned values.
  • the Cmax of the therapeutic agent is equal to or at least about: 0.5 pg/L, 1 pg/L, 2 pg/L, 3 pg/L, 4 pg/L, 5 pg/L, 6 pg/L, or ranges including and/or spanning the aforementioned values.
  • cannabinoids such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the Cmax of the therapeutic agent is equal to or at least about: 0.5 pg/L, 1 pg/L, 2 pg/L, 3 pg/L, 4 pg/L, 5 pg/L, 6 pg/L, or ranges including and/or spanning the aforementioned values.
  • the Cmax is equal to or at least about: 40 ng/mL, 50 ng/mL, 60 ng/mL, 70 ng/mL, 80 ng/mL, 90 ng/mL, 100 ng/mL, 150 ng/mL, 200 ng/mL, or ranges including and/or spanning the aforementioned values.
  • therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the Cmax is equal to or at least about: 40 ng/mL, 50 ng/mL, 60 ng/mL, 70 ng/mL, 80 ng/mL, 90 ng/mL, 100 ng/mL, 150 ng/mL, 200 ng/mL, or ranges including and/or spanning the aforementioned
  • the Cmax for a disclosed embodiment is increased relative to an equal dose of a therapeutic agent (e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing) in an oil-based comparator vehicle.
  • a therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • an oil-based comparator vehicle e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the Cmax for a disclosed embodiment is increased relative to an oil-based comparator vehicle by equal to or at least about: 15%, 20%, 50%, 100%, 150%, 200%, or
  • these pharmacokinetic results can be achieved using aqueous compositions or powdered compositions (where the powder is supplied by itself, in a gel capsule, as an additive to food, etc.).
  • the Cmax using a disclosed embodiment is 1.25 times higher than when using a comparator delivery system (e.g., the Cmax of the comparator x 1.25). In some instances, the Cmax using a disclosed embodiment is equal to or at least about 1.25 times higher, 1.5 times higher, 2 times higher, 3 times higher (or ranges including or spanning the aforementioned values) than when using a comparator delivery system.
  • a composition disclosed herein may achieve a more steady release of therapeutic. This may be reflected by a lower Cmax when compared to some comparator compositions.
  • the Cmax for a disclosed embodiment is decreased relative to an equal dose of a therapeutic agent (e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing) in an comparator vehicle.
  • a therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the Cmax for a disclosed embodiment is decreased relative to a comparator vehicle by equal to or at least about: 15%, 20%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values. In several embodiments, these pharmacokinetic results can be achieved using aqueous compositions or powdered compositions (where the powder is supplied by itself, in a gel capsule, as an additive to food, etc.).
  • the Cmax using a disclosed embodiment is 1.25 times lower than when using a comparator delivery system. In some instances, the Cmax using a disclosed embodiment is equal to or at least about 1.25 times lower, 1.5 times lower, 2 times lower, 3 times lower (or ranges including or spanning the aforementioned values) than when using a comparator delivery system.
  • the Tmax for a therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • a therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • a disclosed embodiment is shortened relative to other vehicles.
  • the Tmax is equal to or at less than about: 30 minutes, 1 hours, 2 hours, 3 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 8 hours, or ranges including and/or spanning the aforementioned values.
  • therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the Tmax is equal to or at less than about: 30 minutes, 1 hours, 2 hours, 3 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 8 hours, or ranges including and/or spanning the aforementioned values.
  • the Tmax is equal to or at less than about: 30 minutes, 1 hours, 2 hours, 3 hours, 4 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 8 hours, or ranges including and/or spanning the aforementioned values.
  • therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the Tmax is equal to or at less than about: 30 minutes, 1 hours, 2 hours, 3 hours, 4 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 8 hours, or ranges including and/or spanning the aforementioned values.
  • the Tmax is between about 4 hours and about 6.5 hours or between about 3 hours and about 7 hours.
  • therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the Tmax is between about 4 hours and about 6.5 hours or between about 3 hours and about 7 hours.
  • the Tmax is equal to or less than about: 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, or ranges including and/or spanning the aforementioned values.
  • the Tmax for the therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the Tmax is improved relative to oil-based vehicles (e.g., has a shorter duration to Tmax).
  • the Tmax is shortened relative to comparable delivery vehicles (e.g., an oil-based vehicle) by equal to or at least about: 5%, 10%, 15%, 20%, 25%, 50%, or ranges including and/or spanning the aforementioned values.
  • the Tmax is shortened relative to the therapeutic agent(s) alone by equal to or at least about: 5%, 10%, 15%, 20%, 25%, or ranges including and/or spanning the aforementioned values. In several embodiments, the Tmax for a disclosed embodiment is decreased relative to an oil-based comparator vehicle by equal to or at least about: 15%, 20%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values.
  • the Tmax of a therapeutic agent for a disclosed embodiment is decreased relative to an oil-based comparator vehicle by equal to or at least about: 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, or ranges including and/or spanning the aforementioned values.
  • the Tmax is a fraction of that achieved using a comparator delivery system.
  • the time to Tmax using a disclosed embodiment is 0.5 times, 0.7 times, 0.8 times, 0.9 times, or 0.95 times the Tmax of a comparator delivery system (or ranges including or spanning the aforementioned values).
  • the AUC is equal to or at least about: 50 ng/mL*hr, 100 ng/mL*hr, 200 ng/mL*hr, 300 ng/mL*hr, 400 ng/mL*hr, 450 ng/mL*hr, 500 ng/mL*hr, 550 ng/mL*hr, 600 ng/mL*hr, 650 ng/mL*hr, 700 ng/mL*hr, 800 ng/mL*hr, 1000 ng/mL*hr, or ranges including and/or spanning the aforementioned
  • the AUC for a therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • a therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • a therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the AUC for a therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the AUC using a disclosed embodiment is increased (relative to a therapeutic agent itself or a comparator delivery vehicle) by equal to or at least about: 5%, 10%, 20%, 30%, or ranges including and/or spanning the aforementioned values.
  • the AUC is improved relative to a therapeutic agent alone or in an oil mixture by equal to or at least about: 5%, 25%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values.
  • the AUC using a disclosed embodiment is 1.25 times higher than when using a comparator delivery system.
  • the AUC using a disclosed embodiment is equal to or at least about 1.25 times higher, 1.5 times higher, 2 times higher, 3 times higher (or ranges including or spanning the aforementioned values) than when using a comparator delivery system.
  • the AUC for the time period from administration to 4 hours post administration using a disclosed embodiment is equal to or at least about: 40 ng/mL*hr, 50 ng/mL*hr, 75 ng/mL*hr, 100 ng/mL*hr, 200 ng/mL*hr, 300 ng/mL*hr, 400 ng/mL*hr, 450 ng/mL*hr, or ranges including and/or spanning the aforementioned values.
  • the AUC for the time period from administration to 4 hours post administration using a disclosed embodiment is increased (e.g., relative to the therapeutic alone or a comparator delivery vehicle) by equal to or at least about: 15 ng/mL*hr, 25 ng/mL*hr, 50 ng/mL*hr, 75 ng/mL*hr, or ranges including and/or spanning the aforementioned values.
  • therapeutic agent e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the AUC for the time period from administration to 4 hours post administration using a disclosed embodiment is increased (e.g., relative to the therapeutic alone or a comparator delivery vehicle) by equal to or at least about: 15 ng/mL*hr, 25 ng/mL*hr, 50 ng/mL*hr, 75 ng/mL*hr, or range
  • the AUC for the time period from administration to 4 hours post administration using a disclosed embodiment is increased (e.g., relative to the therapeutic alone or a comparator delivery vehicle) by equal to or at least about: 5%, 10%, 20%, 25%, 30%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values.
  • the AUC for the time period from administration to 4 hours post administration using a disclosed embodiment is double that of a comparator delivery system, triple that of a comparator delivery system, quadruple that of a comparator delivery system, or higher.
  • the AUC for the time period from 4 hours post administration to 6 hours post administration using a disclosed embodiment is equal to or at least about: 40 ng/mL*hr, 50 ng/mL*hr, 75 ng/mL*hr, 100 ng/mL*hr, 200 ng/mL*hr, 300 ng/mL*hr, 400 ng/mL*hr, 450 ng/mL*hr, or ranges including and/or spanning the aforementioned values.
  • the AUC for the time period from 4 hours post administration to 6 hours post administration using a disclosed embodiment is increased (e.g., relative to the therapeutic alone or a comparator delivery vehicle) by equal to or at least about: 15 ng/mL*hr, 25 ng/mL*hr, 50 ng/mL*hr, 75 ng/mL*hr, or ranges including and/or spanning the aforementioned values.
  • therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the AUC for the time period from 4 hours post administration to 6 hours post administration using a disclosed embodiment is increased (e.g., relative to the therapeutic alone or a comparator delivery vehicle) by equal to or at least about: 15 ng/mL*hr, 25 ng/mL*hr
  • the AUC for the time period from 4 hours post administration to 6 hours post administration using a disclosed embodiment is increased (e.g., relative to the therapeutic alone or a comparator delivery vehicle) by equal to or at least about: 5%, 10%, 20%, 25%, 30%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values.
  • therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the AUC for the time period from 4 hours post administration to 6 hours post administration using a disclosed embodiment is increased (e.g., relative to the therapeutic alone or a comparator delivery vehicle) by equal to or at least about: 5%, 10%, 20%, 25%, 30%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values.
  • the AUC for the time period from 4 hours post administration to 6 hours post administration using a disclosed embodiment is double that of a comparator delivery system, triple that of a comparator delivery system, quadruple that of a comparator delivery system, or higher.
  • the half-life for a therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • cannabinoids such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the ti/2 of therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the ti/2 of therapeutic agent is equal to or at less than about: 4 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, or ranges including and/or spanning the aforementioned values.
  • the ti/2 of therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the ti/2 of therapeutic agent is between about 4 hours and about 6.5 hours or between about 3 hours and about 7 hours.
  • the ti/2 for a disclosed embodiment is decreased relative to a therapeutic agent alone or an oil-based comparator vehicle by equal to or at least about: 15%, 20%, 50%, 100%, 150%, 200%, or ranges including and/or spanning the aforementioned values.
  • the ti/2 of therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the ti/2 is a fraction of that achieved using a comparator delivery system.
  • the time to ti/2 using a disclosed embodiment is 0.5 times, 0.7 times, 0.8 times, 0.9 times, or 0.95 times the ti/2 of a comparator delivery system (or ranges including or spanning the aforementioned values).
  • the Cmax, Tmax, AUC, and ti/2 results provided are disclosed with specific reference to CBD as the active agent.
  • the above pharmacokinetic results are also expected for other phytocannabinoids, a fungus extract, a kratom extract, a Kanna extract, a kava extract, a hemp extract, a cannabis extract, and/or other therapeutic agents as disclosed elsewhere herein.
  • the lipid-based particle composition comprises nanoparticles having an average size of less than or equal to about: 10 nm, 50 nm, 100 nm, 250 nm, 500 nm, 1000 nm, or ranges including and/or spanning the aforementioned values. In several embodiments, the composition comprises nanoparticles having an average size of between about 50 nm and 150 nm or between about 50 and about 250 nm.
  • the size distribution of the nanoparticles for at least 50%, 75%, 80%, 90% (or ranges including and/or spanning the aforementioned percentages) of the particles present is equal to or less than about: 20 nm, 40 nm, 60 nm, 80 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 160 nm, 180 nm, 200 nm, 300 nm, 400 nm, 500 nm, or ranges including and/or spanning the aforementioned nm values.
  • the composition comprises nanoparticles having an average size of less than or equal to about: 10 nm, 50 nm, 100 nm, 250 nm, 500 nm, 1000 nm, or ranges including and/or spanning the aforementioned values.
  • the size distribution of the nanoparticles for at least 90% of the particles present is equal to or less than about: 20 nm, 40 nm, 60 nm, 80 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 160 nm, 180 nm, 200 nm, 300 nm, 400 nm, 500 nm, or ranges including and/or spanning the aforementioned nm values.
  • the size distribution of the nanoparticles for at least 90% of the particles present is equal to or less than about: 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 160 nm, 180 nm, 200 nm, or ranges including and/or spanning the aforementioned nm values.
  • the D90 of the particles present is equal to or less than about: 80 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 160 nm, 180 nm, 200 nm, 300 nm, 400 nm, 500 nm, or ranges including and/or spanning the aforementioned values.
  • the size of the nanoparticle is the diameter of the nanoparticle as measured using any of the techniques as disclosed elsewhere herein. For instance, in several embodiments, the size of the nanoparticle is the measured using dynamic light scattering. In several embodiments, the size of the nanoparticle is the measured using a zeta sizer.
  • the average size of the nanoparticles of a composition as disclosed herein is substantially constant and/or does not change significantly over time (e.g., it is a stable nanoparticle).
  • the average size of nanoparticles comprising the composition changes less than or equal to about: 1%, 5%, 10%, 20%, or ranges including and/or spanning the aforementioned values.
  • the polydispersity index (PDI) of the nanoparticles of a composition as disclosed herein is less than or equal to about: 0.05, 0.10, 0.15, 0.20, 0.25, 0.30, 0.40, 0.50, 0.60, 0.70, 0.80, or ranges including and/or spanning the aforementioned values.
  • the size distribution of the nanoparticles is highly monodisperse with a polydispersity index of less than or equal to about: 0.05, 0.10, 0.15, 0.20, 0.25, or ranges including and/or spanning the aforementioned values.
  • the zeta potential of the nanoparticles of a composition as disclosed herein is less than or equal to about: 1 mV, 3 mV, 4 mV, 5 mV, 6 mV, 7 mV, 8 mV, 10 mV, 20 mV, or ranges including and/or spanning the aforementioned values.
  • the zeta potential of the nanoparticles is greater than or equal to about: -3 mV, -1 mV, 0 mV, 1 mV, 3 mV, 4 mV, 5 mV, 6 mV, 7 mV, 8 mV, 4 mV, 10 mV, 20 mV, or ranges including and/or spanning the aforementioned values.
  • the zeta potential and/or diameter of the particles is acquired using a zetasizer (e.g., a Malvern ZS90 or similar instrument).
  • the lipid-based particle composition has a pH of less than or equal to about: 2, 3, 4, 5, 6, 6.5, 7, 8, 9, or ranges including and/or spanning the aforementioned values. In several embodiments, the composition has a pH of greater than or equal to about: 2, 3, 4, 5, 6, 6.5, 7, 8, 9, or ranges including and/or spanning the aforementioned values.
  • the lipid-based particle composition is stable.
  • the polydispersity of the nanoparticles changes less than or equal to about: 1%, 5%, 10%, 20%, or ranges including and/or spanning the aforementioned values.
  • the soluble fraction of therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing
  • the soluble fraction of therapeutic agent in the formulation changes less than or equal to about: 1%, 5%, 10%, 20%, 30%, or ranges including and/or spanning the aforementioned values.
  • the PDI of nanoparticles comprising the composition changes by less than or equal to about: 1%, 5%, 10%, 20%, or ranges including and/or spanning the aforementioned values.
  • the PDI of nanoparticles comprising the composition changes by less than or equal to about: 0.05, 0.1, 0.2, 0.3, 0.4, or ranges including and/or spanning the aforementioned values.
  • the average size of nanoparticles comprising the composition changes by less than or equal to about: 10%, 20%, 30%, 40%, 50%, 100%, or ranges including and/or spanning the aforementioned values.
  • the D90 of nanoparticles comprising the composition changes by less than or equal to about: 10%, 20%, 30%, 40%, 50%, 100%, or ranges including and/or spanning the aforementioned values.
  • the particle size of the nanoparticles of a composition as disclosed herein does not change and/or changes less than 5% during a period of greater than or equal to about: 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 10 hours, or ranges including and/or spanning the aforementioned values.
  • the particle size of the nanoparticles disclosed herein when exposed to simulated intestinal fluid (e.g., at a concentration of 20 mg/mL), does not change and/or changes less than 5% during a period of greater than or equal to about: 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 10 hours, or ranges including and/or spanning the aforementioned values.
  • the average particle size of nanoparticles comprising the composition changes by less than or equal to about: 1%, 5%, 10%, 20%, 50%, or ranges including and/or spanning the aforementioned values.
  • the PDI of nanoparticles comprising the composition changes by less than or equal to about: 1%, 5%, 10%, 20%, or ranges including and/or spanning the aforementioned values.
  • the PDI of nanoparticles comprising the composition changes by less than or equal to about: 0.01, 0.05, 0.1, 0.2, 0.3, or ranges including and/or spanning the aforementioned values.
  • the average particle size of nanoparticles comprising the composition changes by less than or equal to about: 1%, 5%, 10%, 20%, 50%, or ranges including and/or spanning the aforementioned values.
  • the PDI of nanoparticles comprising the composition changes by less than or equal to about: 1%, 5%, 10%, 20%, 100%, 150%, or ranges including and/or spanning the aforementioned values.
  • the PDI of nanoparticles comprising the composition changes by less than or equal to about: 0.01, 0.05, 0.1, 0.2, 0.3, or ranges including and/or spanning the aforementioned values.
  • the composition particle size remains consistent (a size change of less than or equal to about: 0%, 0.5%, 1%, 2%, 3%, 5%, or ranges including and/or spanning the aforementioned values) for a period of at least about 30 days when stored at room temperature, refrigeration, and up to 40°C.
  • the therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • concentration in the composition remains consistent (a loss of less than or equal to about: 0.5%, 1%, 2%, 3%, 5%, or ranges including and/or spanning the aforementioned values) for a period of at least about 30 days, 60 days, 90 days, or 120 days when stored at room temperature, refrigeration, and up to 40°C.
  • the composition when stored at room temperature, refrigeration, and up to 40°C, the composition is stable (e.g., the particle size or therapeutic agent concentration in the nanoparticles remains consistent and/or has a change of less than or equal to about: 0.5%, 1%, 2%, 5%, or ranges including and/or spanning the aforementioned values) for a period of at least about: 2 weeks, 30 days, 2 months, 3 months, 6 months, 9 months, 1 year, or ranges including and/or spanning the aforementioned measures of time.
  • the method of using the lipid-based particle composition and/or of treating a subject with the lipid-based particle composition includes administering to a subject in need of treatment (e.g., orally, topically, etc.) an effective amount of the composition.
  • the composition e.g., delivery system
  • the bioavailability of the therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • cannabinoids such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the initial administered dose is greater than or equal to about: 10%, 20%, 50%, 75%, or ranges including and/or spanning the aforementioned values.
  • the oral bioavailability of the therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the oral bioavailability is improved over the therapeutic alone by greater than or equal to about: 10%, 50%, 75%, 100%, 200%, or ranges including and/or spanning the aforementioned values.
  • the method of treating comprises selecting patient for treatment.
  • the method of threating comprises administering to the patient an effective amount of a formulation comprising a lipid-based particle composition comprising a therapeutic agent (e.g., cannabinoids, such as CBD, non-cannabinoid therapeutic agents, and combinations thereof).
  • a therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoid therapeutic agents, and combinations thereof.
  • compositions as described herein may be used to induce at least one effect, e.g. therapeutic effect, that may be associated with at least one therapeutic agent (e.g., cannabinoids, such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing), which is capable of inducing, enhancing, arresting or diminishing at least one effect, by way of treatment or prevention of unwanted conditions or diseases in a subject.
  • the at least one active agent may be selected amongst therapeutic agents, i.e.
  • the phospholipid, non-phospholipid lipid, sterol, etc. by themselves do not induce or modulate a therapeutic effect but endow the composition (e.g., a pharmaceutical composition) with a selected desired characteristic.
  • compositions disclosed herein e.g., lipid-based particle compositions including fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), other therapeutics, or combinations of any of the foregoing
  • lipid-based particle compositions including fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), other therapeutics, or combinations of any of the foregoing
  • fungus extract(s) e.g., lipid-based particle compositions including fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), other therapeutics, or combinations of any of the foregoing
  • the subject is treated by administering an effective amount of a composition (e.g., lipid-based particle compositions including fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), other therapeutics, or combinations of any of the foregoing) as disclosed herein to the subject.
  • a composition e.g., lipid-based particle compositions including fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), other therapeutics, or combinations of any of the foregoing
  • the disease or condition to be treated via administration of a composition may include one or more of liver protection, hangover prevention, vitamin deficiency, alcohol related heart disease, alcohol related neurological conditions, opioid withdraw, attention deficient disorder (ADHD), pain, anxiety, depression, seizures, malaise, nausea, insomnia, work-sleep shift disorder, sleep disturbances, inflammation, immunity, epilepsy, diabetes, cancer (breast, colon, prostate, glioma, etc.), etc.
  • the composition e.g., a composition comprising one or more of a hemp extract, a cannabis extract, a mushroom extract, a kratom extract, a kanna extract, a kava extract, combinations of the foregoing, etc.
  • a cerebrocirculant an antiaggregant, an anti- adrenergic at alpha- 1, a sedative, an anticonvulsant, a smooth muscle relaxer, an antitussive, an analgesic, a p-opioid antagonist, a calcium channel blocker, a dopamine mediating anti-locomotive, an antioxidant, an antiaggregant, an antibacterial, an antidiabetic, an antihepatitic, an anti-inflammatory, an anti-leukemic, an antimutagenic, an antiperoxidant, an antiviral, a cancer preventative, an alpha-amylase inhibitor, a 9- hydroxycorynantheidine, an
  • the composition e.g., a composition comprising one or more of a hemp extract, a cannabis extract, a mushroom extract, a kratom extract, a kanna extract, a kava extract, combinations of the foregoing, etc.
  • a disease or disorder where any one or more of the following is needed: a cerebrocirculant, an antiaggregant, an anti- adrenergic at alpha- 1, a sedative, an anticonvulsant, a smooth muscle relaxer, an antitussive, an analgesic, a p-opioid antagonist, a calcium channel blocker, a dopamine mediating anti-locomotive, an antioxidant, an antiaggregant, an antibacterial, an antidiabetic, an antihepatitic, an anti-inflammatory, an anti-leukemic, an antimutagenic, an antiperoxidant, an antiviral, a cancer preventative, an alpha-amy
  • the lipid-based particle composition (e.g., those including fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), other therapeutics, or combinations of any of the foregoing) is provided for use in treating a condition selected from pain associated disorders (as an analgesic), inflammatory disorders and conditions (as anti-inflammatory), appetite suppression or stimulation (as anoretic or stimulant), symptoms of vomiting and nausea (as antiemetic), intestine and bowl disorders, disorders and conditions associated with anxiety (as anxiolytic), disorders and conditions associated with psychosis (as antipsychotic), disorders and conditions associated with seizures and/or convulsions (as antiepileptic or antispasmodic), sleep disorders and conditions (as anti-insomniac), disorders and conditions which require treatment by immunosuppression, disorders and conditions associated with elevated blood glucose levels (as antidiabetic), disorders and conditions associated with nerve
  • the lipid-based particle composition (e.g., those comprising fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), other therapeutics, or combinations of any of the foregoing) is provided for use in a method of treating a subject suffering from a condition selected from pain associated disorders, inflammatory disorders and conditions, symptoms of vomiting and nausea, intestine and bowl disorders, disorders and conditions associated with anxiety, disorders and conditions associated with psychosis, disorders and conditions associated with seizures and/or convulsions, sleep disorders and conditions, disorders and conditions which require treatment by immunosuppression, disorders and conditions associated with elevated blood glucose levels, disorders and conditions associated with nerve system degradation, inflammatory skin disorders and conditions, disorders and conditions associated with artery blockage, disorders and conditions associated with bacterial infections, disorders and conditions associated with fungal infections, proliferative disorders and conditions, and disorders and conditions associated with inhibited bone growth, post trauma disorders and others, a patient in need of appetite
  • the lipid-based particle compositions may be used for inducing, enhancing, arresting or diminishing at least one effect, by way of treatment or prevention of unwanted conditions or diseases in a subject.
  • the therapeutic agent (substance, molecule, element, compound, entity, or a combination thereof) may be selected amongst therapeutic agents, i.e. agents capable of inducing or modulating a therapeutic effect when administered in a therapeutically effective amount, and non- therapeutic agents, i.e. which by themselves do not induce or modulate a therapeutic effect but which may endow the pharmaceutical composition with a selected desired characteristic.
  • a lipid-based particle compositions as disclosed herein may be selected to treat, prevent or ameliorate any pathology or condition.
  • a pharmaceutical composition comprising fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), other therapeutics, or combinations of any of the foregoing
  • administering of a therapeutic amount of the composition or system described herein, whether in a concentrate form or in a diluted formulation form, is effective to ameliorate undesired symptoms associated with a disease, to prevent the manifestation of such symptoms before they occur, to slow down the progression of the disease, slow down the deterioration of symptoms, to enhance the onset of remission period, slow down the irreversible damage caused in the progressive chronic stage of the disease, to delay the onset of said progressive stage, to lessen the severity or cure the disease, to improve survival rate or more rapid recovery, or to prevent the disease from occurring or a combination of two or more of the above.
  • the lipid-based particle compositions disclosed herein lack, contain less than 2%, and/or less than about 0.5% of one or more of lecithin surfactants, hyaluronic acid, Alcolec S, Alcolec BS, Alcolec XTRA-A, polysorbates (such as Polysorbate 80 and Polysorbate 20), monoglycerides, diglycerides, glyceryl oleate, polaxamers, terpenes, sodium alginate, polyvinylpyrrolidone, L-alginate, chondroitin, poly gamma glutamic acid, gelatin, chitosan, com starch, polyoxyl 40-hydroxy castor oil, Tween 20, Span 80, or the salts of any of thereof.
  • lecithin surfactants such as Polysorbate 80 and Polysorbate 20
  • polysorbates such as Polysorbate 80 and Polysorbate 20
  • monoglycerides diglycerides, glyceryl ole
  • the lipid-based particle compositions disclosed herein lack, contain less than 2%, and/or less than about 0.5% of a surfactant. In several embodiments, the lipid-based particle compositions disclosed herein (or the active ingredients within these compositions, e.g., cannabinoids) lack, contain less than 3%, contain less than 2%, and/or less than about 0.5% of one or more of THCa, 9-THC, 8-THC, CBDa, CBC, CBG, CBN, THCV, and/or CBGa, individually or collectively.
  • the CBD lipid-based particle compositions disclosed herein lack, contain less than 2%, and/or less than about 0.5% of one or more of THCa, 9-THC, 8-THC, CBDa, CBC, CBG, CBN, THCV, and/or CBGa.
  • the lipid-based particle compositions lack unhydrogenated phospholipids.
  • the lipid-based particle compositions lack hydrogenated phospholipids.
  • the lipid-based particle compositions comprise one or more unhydrogenated or hydrogenated phospholipids.
  • the lipid-based particle compositions disclosed herein lack, contain less than 2%, and/or less than about 0.5% of one or more of a buffering agent, a polymeric stabilizing agent, or sodium hydroxide.
  • the lipid-based particle compositions disclosed herein lack a nanoparticle structure wherein the structure comprises an outer single layer membrane of essential phospholipids that encapsulates liquid lipids and cannabinoids.
  • essential phospholipids are extracts of characteristic fatty acid lipid-based particle composition of the phospholipids distinguished by their particular high content of polyunsaturated fatty acids, predominantly linoleic acid (approx. 70%), linolenic acid and oleic acid and with a high content exceeding 75% of (3-sn-phosphatidyl) choline.
  • the essential phospholipid fraction includes phosphatidylethanolamine, phosphatidylinositol and other lipids.
  • the lipid-based particle compositions disclosed herein lack nonnatural ingredients.
  • the lipid-based particle compositions disclosed are synthetic and not found in nature.
  • the lipid-based particle compositions disclosed herein lack, contain less than 2%, and/or less than about 0.5% of one or more organic bases (which may include, but are not limited to: butyl hydroxyl anisole (BHA), butyl hydroxyl toluene (BHT) and sodium ascorbate). In several embodiments, the lipid-based particle compositions disclosed herein lack, contain less than 2%, and/or less than about 0.5% of whey protein isolate. In several embodiments, the lipid-based particle compositions disclosed herein lack, contain less than 2%, and/or less than about 0.5% of ticamulsion 3020, purity gum, gum Arabic, and/or a modified gum Arabic.
  • organic bases which may include, but are not limited to: butyl hydroxyl anisole (BHA), butyl hydroxyl toluene (BHT) and sodium ascorbate.
  • BHA butyl hydroxyl anisole
  • BHT butyl hydroxyl toluene
  • sodium ascorbate
  • the lipid-based particle compositions disclosed herein lack, contain less than 2%, and/or less than about 0.5% one or more of fatty acids, triglycerides triacylglycerols, acylglycerols, fats, waxes, sphingolipids, glycerides, sterides, cerides, glycolipids, sulfolipids, lipoproteins, chylomicrons and the derivatives of these lipids. In several embodiments, the lipid-based particle compositions disclosed herein lack, contain less than 2%, and/or less than about 0.5% of a surfactant.
  • the lipid-based particle compositions disclosed herein lack, contain less than 2%, and/or less than about 0.5% of one or more of polyglycolized glycerides and polyoxyethylene glycerides of medium to long chain mono-, di-, and triglycerides, such as: almond oil PEG-6 esters, almond oil PEG-60 esters, apricot kernel oil PEG-6 esters (Labrafil® M1944CS), caprylic/capric triglycerides PEG-4 esters (Labrafac® Hydro WL 1219), caprylic/capric triglycerides PEG-4 complex (Labrafac® Hydrophile), caprylic/capric glycerides PEG-6 esters (Softigen® 767), caprylic/capric glycerides PEG-8 esters (Labrasol®), castor oil PEG-50 esters, hydrogenated castor oil PEG-5 esters, hydrogenated castor oil PEG-7 esters, 9 hydrogenated castor oil P
  • Labrafil® Isostearique triolein PEG-6 esters, trioleate PEG-25 esters, polyoxyl 35 castor oil (Cremophor® EL or Kolliphor® EL), polyoxyl 40 hydrogenated castor oil (Cremophor® RH 40 or Kolliphor® RH40), polyoxyl 60 hydrogenated castor oil (Cremophor® RH60), polyglycolized derivatives and polyoxyethylene esters or ethers derivatives of medium to long chain fatty acids, propylene glycol esters of medium to long chain fatty acids, which can be used including caprylate/caprate diglycerides, glyceryl monooleate, glyceryl ricinoleate, glyceryl laurate, glyceryl dilaurate, glyceryl dioleate, glyceryl mono/dioleate, polyglyceryl- 10 trioleate, poly glyceryl- 10 laurate, polyglyceryl- 10
  • Some embodiments also encompass methods for making (as disclosed elsewhere herein) and for administering the disclosed compositions.
  • Multiple techniques of administering the lipid-based particle compositions as disclosed herein exist including, but not limited to, oral, rectal, topical, aerosol, injection and parenteral delivery, including intramuscular, subcutaneous, intravenous, intramedullary injections, intrathecal, direct intraventricular, intraperitoneal, intranasal and intraocular injections.
  • administration is performed through oral pathways, which administration includes administration in an emulsion, capsule, tablet, film, chewing gum, suppository, granule, pellet, spray, syrup, or other such forms.
  • modes of administration include modes of administration through intraocular, intranasal, and intraauricular pathways.
  • topical permeation enhancers may be included and may be selected from, but not inclusive of, the following: dimethyl sulfoxide, dimethyl sulfone, ethanol, propylene glycol, dimethyl isosorbide, polyvinyl alcohol, CapryolTM 90, Labrafil Ml 944 CS, Labrasol, Labrasol ALF, LauroglycolT M90, Transcutol HP, Capmul S12L, Campul PG-23 EP/NF, Campul PG-8 NF.
  • the topical may include one or more of Lipoid’s Skin Lipid Matrix 2026 technology, lipid/oil based ingredients or oil soluble ingredients, and includes Captex 170 EP as a skin permeation enhancer, argan oil, menthol, arnica oil, camphor, grapefruit seed oil, For example, dimethyl sulfoxide, dimethyl isosorbide, topical analgesics such as lidocaine, wintergreen oil, and terpenes such as guaiacol.
  • Lipoid Skin Lipid Matrix 2026 technology
  • lipid/oil based ingredients or oil soluble ingredients includes Captex 170 EP as a skin permeation enhancer, argan oil, menthol, arnica oil, camphor, grapefruit seed oil,
  • dimethyl sulfoxide dimethyl isosorbide
  • topical analgesics such as lidocaine, wintergreen oil, and terpenes such as guaiacol.
  • any one or more of these ingredients is present in the topical composition at a dry wt % of equal to or less than about: 0.1%, 0.5%, 1%, 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, or ranges including and/or spanning the aforementioned values. In several embodiments, any one or more of these ingredients is present in the topical at a wet wt % of equal to or at least about: 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 20%, 30%, or ranges including and/or spanning the aforementioned values.
  • the lipid-based particle compositions disclosed herein can be in admixture with a suitable carrier, diluent, or excipient such as sterile water, physiological saline, glucose, or the like, and can contain auxiliary substances such as wetting or emulsifying agents, pH buffering agents, gelling or viscosity enhancing additives, preservatives, flavoring agents, colors, and the like, depending upon the route of administration and the preparation desired.
  • a suitable carrier diluent, or excipient
  • auxiliary substances such as wetting or emulsifying agents, pH buffering agents, gelling or viscosity enhancing additives, preservatives, flavoring agents, colors, and the like, depending upon the route of administration and the preparation desired.
  • Such preparations can include liposomes, microemulsions, micelles, and/or unilamellar or multilamellar vesicles.
  • the lipid-based particle compositions are suspended in a broth providing a lipid-based particle suspension solution.
  • the broth is a liquid medium containing proteins and/or other nutrients for the culture of bacteria.
  • the lipid-based particle suspension solution disclosed herein have improved shelf life as indicated in part by the ability of the lipid-based particle composition to remain suspended in the liquid broth without aggregating or separating/settling from solution.
  • the lipid-based particle suspension solution disclosed remain solubilized for a period greater than or equal to 6 months, 12 months, 14 months, 16 months, 18 months, 19 months, or ranges including and/or spanning the aforementioned values.
  • the shelf life can be determined as the period of time in which there is 95% confidence that at least 50% of the response (therapeutic agent(s) concentration or particle size) is within the specification limit.
  • the response variable is either Z-average particle size or therapeutic agent (e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing) concentration in Figures 3 and 4.
  • the particle size specification is 100 to 200 nm
  • the therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing concentration specification is 18 to 22 mg / mL.
  • the shelf life determined as a time where the concentration of the active ingredient has changed (e.g., lessened) by less than or equal to 15%, 10%, 5%, 2.5%, or ranges including and or spanning the aforementioned ranges.
  • compositions disclosed herein when provided in a lipid-based particle suspension solution, have improved thermal stability.
  • thermal sterilization includes exposing and/or heating a composition to a temperature of equal to or at least about 100 °C. In several embodiments, the thermal sterilization is performed for a time period of equal to or at least about: 10 minutes, 15 minutes, 30 minutes, 60 minutes, or ranges including and/or spanning the aforementioned values.
  • the particle size and/or PDI varies by less than or equal to about: 1%, 5%, 10%, 20%, 30%, or ranges including and/or spanning the aforementioned values.
  • the concentration of the therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the concentration of the therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any of the foregoing
  • the storage conditions include temperatures of equal to or at least about: 2°C, 8°C, 10°C, 20°C, 40°C, 60°C%
  • the compositions disclosed herein when provided in a lipid-based particle suspension solution, are stable during ozonation sterilization, UV sterilization, heat sterilization (e.g., pasteurization), filtration sterilization, and/or gamma irradiation during beverage preparation and packaging.
  • the particle size and/or PDI after sterilization varies by less than or equal to about: 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, or ranges including and/or spanning the aforementioned values.
  • the therapeutic agent e.g., cannabinoids, such as CBD, non-cannabinoids, and/or combinations of any of the foregoing concentration after sterilization (e.g., exposure to techniques that allow sterilization of the composition) drops by less than or equal to about: 0.05%, 0.1%, 0.5%, 1%, 5%, 10%, 15%, or ranges including and/or spanning the aforementioned values.
  • the lipid-based particle suspension solutions comprising lipid-based particle compositions have a shelf life of equal to or greater than 6 months, 12 months, 14 months, 16 months, 18 months, 19 months, or ranges including and/or spanning the aforementioned values (e.g., a standard storage conditions).
  • the ozonation may be performed at a final therapeutic (e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), etc.) concentration of 0.2 mg/mL in water.
  • the ozonation is carried out using a ozonation time (e.g., using a commercial ozone air and water purifier) for a period of equal to or at least about: 1 minute, 5 minutes, 10 minutes, 20 minutes, 30 minutes, 1 hour, or ranges including and/or spanning the aforementioned values.
  • the particle size and/or PDI after ozonation sterilization (e.g., measured directly after sterilization) varies by less than or equal to about: 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2.5%, 5%, or ranges including and/or spanning the aforementioned values.
  • the change in particle size and/or PDI after ozonation relative to a non- sterilized control (e.g., measured one week after sterilization) varies by less than or equal to about: 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2.5%, 5%, 8%, 10%, or ranges including and/or spanning the aforementioned values.
  • the particle size and/or PDI measurement is performed directly after (e.g., substantially immediately) sterilization and/or a week or more after sterilization (e.g., 1 week, two weeks, etc.).
  • the UV treatment may be performed at a final therapeutic (e.g., fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), etc.) concentration of 0.2 mg/mL in water.
  • the UV treatment is carried out using at least 1, 2, 5, 10, UV cycles, or ranges including and/or spanning the aforementioned values.
  • the particle size and/or PDI after UV treatment varies by less than or equal to about: 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2.5%, 5%, or ranges including and/or spanning the aforementioned values.
  • the change in particle size and/or PDI after UV treatment relative to a non-sterilized control varies by less than or equal to about: 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2.5%, 5%, 8%, 10%, or ranges including and/or spanning the aforementioned values.
  • the UV treatment may be performed using UVA, UVB, UVC, full spectrum UV light, and/or combinations of the foregoing.
  • the particle size and/or PDI measurement is performed directly after (e.g., substantially immediately) sterilization and/or a week or more after sterilization (e.g., 1 week, two weeks, etc.).
  • the lipid-based particle composition lacks terpenes (e.g., as impurities or additives). However, in other embodiments, one or more terpenes may be added to prepare the nanoparticle composition.
  • the one or more terpenes includes one or more of alpha fenchone, alpha terpinene, alpha terpineol, beta caryophyllene, alpha pinene, beta pinene, bisabolene, bisabolol, borneol, eucalyptol, gamma terpinene, guaiacol, humulene, linalool, myrcene, para cymene, phytol, and/or terpinolene.
  • the one or more terpenes includes one or more of 7,8-dihydro-alpha-ionone, 7,8-dihydro-beta-ionone, Acetanisole, Acetic Acid, Acetyl Cedrene, Anethole, Anisole, Benzaldehyde, Bergamotene (Alpha-cis- Bergamotene) (Alpha-trans-Bergamotene), Bisabolol (Beta-Bisabolol), Alpha Bisabolol, Borneol, Bornyl Acetate, Butanoic/Butyric Acid, Cadinene (Alpha-Cadinene) (Gamma- Cadinene), cafestol, Caffeic acid, Camphene, Camphor, Capsaicin, Carene (Delta-3-Carene), Carotene, Carvacrol, Dextro-Carvone, Laevo-Carvone, Alpha-Caryophyl
  • the one or more terpenes are present in the aqueous composition at a concentration of less than or equal to about: 400 mg/ml, 300 mg/ml, 200 mg/ml, 150 mg/ml, 100 mg/ml, 75 mg/ml, 50 mg/ml, 25 mg/ml, or ranges including and/or spanning the aforementioned values.
  • the one or more terpenes are present in the composition at a dry wt % of equal to or less than about: 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, or ranges including and/or spanning the aforementioned values.
  • the one or more terpenes are present in the composition at a wet wt % of equal to or less than about: 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 20%, 30%, 40%, or ranges including and/or spanning the aforementioned values.
  • Dry powder formulations or liquid embodiments may also be used in a variety of consumer products.
  • dry powders can be added (e.g., scooped, from a packet, squirted from a dispenser, etc.) into any consumer product.
  • liquid solutions or powdered lipid particle formulations can be coated onto and/or added into a consumer product (e.g., sprayed and/or squirted from a dispenser, through dipping, soaking, rolling, dusting, etc.).
  • the consumer product is a food product (e.g., candies, lollipops, edibles, food, ingestible, buccal adhesives, or others).
  • the consumer product is a biomass.
  • the biomass is a hemp biomass (e.g., the buds and/or nugs of the hemp plant), a marijuana biomass (e.g., the buds and/or nugs of the marijuana plant), a mushroom biomass (plant or powdered plant, cordyceps, lion mane, reishi, chaga gano, psilocybin, or combinations thereof), and/or kratom biomass (plant or powdered plant, Maeng da, Indo, Bali/red vien, Green Malay, or combinations thereof).
  • hemp biomass e.g., the buds and/or nugs of the hemp plant
  • a marijuana biomass e.g., the buds and/or nugs of the marijuana plant
  • a mushroom biomass plant or powdered plant, cordyceps, lion mane, reishi, chaga gano, psilocybin, or combinations thereof
  • kratom biomass plant or powdered plant, Maeng da, Indo, Bali/red vien, Green Mal
  • the biomass is a moonrock (e.g., a marijuana nug dipped in or sprayed with concentrate (e.g., solvent extracted marijuana) and/or hash oil; a moon rock may be further rolled in and/or coated with kief).
  • the biomass is a rosin.
  • the biomass is hash.
  • the biomass is bubble hash.
  • Bubble hash is a cannabis concentrate comprising trichomes, or resinous glands, that have been separated from the plant (e.g., using ice water, agitation, and a sieve).
  • the lipid particles supplement and/or fortify the consumer product (e.g., biomass) with a therapeutic agent from the lipid particles.
  • the therapeutic agent is delivered to the user in a greater quantity than would be achieved using (e.g., consuming) the biomass alone or is not present in the biomass alone.
  • the lipid particles may be used to deliver additional cannabinoids, terpenes, and/or combinations thereof (as disclosed elsewhere herein) to the biomass.
  • the biomass may be fortified with additional cannabinoids, terpenes, and/or combinations thereof (as disclosed elsewhere herein).
  • the biomass is supplemented with CBD, other cannabinoids, non-cannabinoid therapeutics, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any one of the foregoing by spraying a liquid solution onto the biomass (or other consumer product).
  • a product that is fortified with CBD, other cannabinoids, non-cannabinoid therapeutics, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), and/or combinations of any one of the foregoing is provided.
  • these fortifying therapeutic agents can be used to enhance health benefits of the consumer product (e.g., biomass), to change the flavor profile of the consumer product (e.g., biomass), to change the physiological effects of the consumer product (e.g., biomass), and/or to provide other benefits.
  • the consumer product e.g., biomass
  • the flavor profile of the consumer product e.g., biomass
  • the physiological effects of the consumer product e.g., biomass
  • coating is performed with an aqueous or solvent solution of the lipid particles.
  • the solution may be sprayed (e.g., via a spray nozzle, atomizer, etc.) or otherwise coated (e.g., dip-coated, etc.) onto the hemp biomass or marijuana biomass or mushroom biomass or kratom biomass, kava biomass, or combinations thereof.
  • pharmaceutical coating equipment e.g., that used to coat tablets, beads, drug layered/coated films
  • fluid bed technology, film bed technology, dry powder laying technology, and/or combinations thereof are used to coat the biomass.
  • film coating is used.
  • the biomass prior to coating with a liquid solution of lipid particles, the biomass is dried completely. Then, after coating, the fortified biomass is dried. In other implementations, freshly harvested biomass is solution coated (e.g., prior to drying). After coating and/or spraying with the lipid particles, the biomass can then be dried together with the lipid particles to provide a fortified biomass. In several embodiments, as disclosed elsewhere herein, a powder can be used to coat the biomass. In several embodiments, a powder lipid particle formulation is dusted or coated onto either dried or freshly harvested biomass. Additional drying may be performed to afford a consumable fortified product.
  • the biomass is dried prior to coating with a powder lipid particle
  • an additional drying step may optionally be performed (though it may not be required).
  • the dried fortified biomass is suitable for use by a user.
  • the powdered biomass of one plant may be used to coat the biomass of another plant.
  • the fortified biomass is further processed prior to use (e.g., in dried or undried form).
  • milling is used to reduce the size of the coated biomass particles.
  • the milling is a two stage process with a first course milling and then a fine milling.
  • the average particle size of the fortified biomass is such that greater than 50% pass through screen having a mesh size of less than or equal to 100, 150, 200, or ranges spanning and/or including the aforementioned values.
  • the average particle size of the fortified biomass is less than or equal to about: 1000 pm, 500 pm, 200 pm, or ranges including and/or spanning the aforementioned values.
  • the fortified biomass is suitable for delivery to a user.
  • the biomass is smoked or vaporized and inhaled where active agents from the biomass (including the fortifying agents) are delivered as smoke or vapor to the lungs.
  • the fortified biomass is suitable for delivery to a user via the gastrointestinal tract (e.g., as an edible, a food ingredient, a gummy, a coated candy, etc.).
  • coatings can be applied to candies, lollipops, edibles, food, ingestible, buccal adhesives, or others.
  • the lipid particles used in the manufacture of supplemented biomass and/or consumer products may lack one or more lipid ingredients, including lacking one or more of a phosphatidylcholine, a sterol, a medium chain triglyceride, and/or combinations thereof.
  • the lipid type, co- solvent triglyceride size, water type, osmolality is adjusted to provide a suitable coating composition.
  • the lipid particle formulation can be remote loaded with therapeutic agents (cannabinoids, non-cannabinoid therapeutics, terpenes, fungus extract(s), kratom extract(s), Kanna extract(s), kava extract(s), hemp extract(s), cannabis extract(s), etc.).
  • a liquid formulation of lipid particles is adding to a therapeutic agent.
  • the therapeutic agent incorporates into the particles by hydrophobic/hydrophilic interactions, electrostatic interactions, etc.
  • a remote loaded product could be coated onto biomass (as disclosed above), dried, and/or milled to provide a fortified, finished product.
  • the lipid particle can be provided with or without a therapeutic agent inside prior to remote loading. Then, other therapeutic agents (cannabinoids, non-cannabinoid therapeutics, etc.) can be loaded into that particle through remote loading.
  • the remote loaded therapeutic is THC.
  • THC cannabinoids
  • the lipid-based particle composition as disclosed herein may be added, injected, measured, and/or poured into kombucha products and/or other fermented caffeinated beverages. It has been noted that the lipid-based particle composition provide increased stability to various therapeutic ingredients and agents as provided herein (including cannabinoids, such as, CBD). In several embodiments, the lipid-based particle composition is added to the kombucha product and/or other fermented caffeinated beverage as a dry solid or as a concentrated solution lipid particle solution (e.g., an aqueous composition as provided elsewhere herein).
  • the lipid-based particle composition is provided in the kombucha product (and/or other fermented caffeinated beverage) at a concentration that is equal to or at least about: 10 pg/mL (or “mcg/mL”), 50 pg/mL, 100 pg/mL, 150 pg/mL, 200 pg/mL, 250 pg/mL, 350 pg/mL, 450 pg/mL, 500 pg/mL, 750 pg/mL, 1 mg/mL, 1.25 mg/mL, 1.5 mg/mL, 1.75 mg/mL, 1.80 mg/mL, 2.0 mg/mL, 2.25 mg/mL, 2.5 mg/mL, 2.6 mg/mL, 3.0 mg/mL, 4.0 mg/mL, 5.0 mg/mL, or ranges including and/or spanning
  • enough of the lipid-based particle composition is added to afford a total concentration of active ingredient in the kombucha product (and/or other fermented caffeinated beverage) of equal to or at least about: 1 pg/mL (or “mcg/mL”), 5 pg/mL, 10 pg/mL, 15 pg/mL, 20 pg/mL, 25 pg/mL, 35 pg/mL, 45 pg/mL, 50 pg/mL, 75 pg/mL, 100 pg/mL, 125 pg/mL, 150 pg/mL, 175 pg/mL, 180 pg/mL, 200 pg/mL, 225 pg/mL, 250 pg/mL, 500 pg/mL, or ranges including and/or spanning the aforementioned values.
  • a concentrated lipid-based particle composition in aqueous solution is added to the kombucha product (and/or other fermented caffeinated beverage
  • each milliliter of kombucha product (and/or other fermented caffeinated beverage) is added equal to or at least about: 0.1 pL, 0.25 pL, 0.5 pL, 0.75 pL, 1 pL, 2.5 pL, 5.0 pL, 7.5 pL, 10 pL, 25 pL, 50 pL, 75 pL, 100 pL, 250 pL, or 500 pL of the concentrated lipid-based particle solution (or ranges including and/or spanning the aforementioned values).
  • compositions and methods have been disclosed. Although this disclosure has been described in terms of certain illustrative embodiments and uses, other embodiments and other uses, including embodiments and uses which do not provide all the features and advantages set forth herein, are also within the scope of this disclosure. Components, elements, features, acts, or steps can be arranged or performed differently than described and components, elements, features, acts, or steps can be combined, merged, added, or left out in various embodiments. All possible combinations and subcombinations of elements and components described herein are intended to be included in this disclosure. No single feature or group of features is necessary or indispensable.
  • the terms “approximately,” “about,” and “substantially” as used herein represent an amount close to the stated amount that still performs a desired function or achieves a desired result. For example, in several embodiments, as the context may dictate, the terms “approximately”, “about”, and “substantially” may refer to an amount that is within less than or equal to 10% of the stated amount.
  • the term “generally” as used herein represents a value, amount, or characteristic that predominantly includes or tends toward a particular value, amount, or characteristic.
  • the ingredients used herein were obtained from the following vendors: Sunflower derived phosphatidylcholine and medium chain triglycerides were purchased from American Lecithin Company (a Lipoid Company listed as “MCT”), potassium sorbate, peppermint oil, vitamin E, malic acid, and cholesterol were purchased from Spectrum Chemicals, CBD isolate was purchased from Botanical & Bioscience Laboratories, Luo Han Guo (monk fruit) extract was purchased from GLG Life Tech Corporation, water for injection was purchased from Rocky Mountain Biologicals, and citric acid monohydrate and sodium benzoate were purchased from JT Baker.
  • the CBD isolate used comprised not more than 0.3% THC by weight per weight (w/w).
  • the phosphatidylcholine was H 100-3 grade including over 96.3% or 99.9 % phosphatidylcholine (hydrogenated).
  • Residual solvents and pesticides were measured by gas chromatography (GC), and heavy metals by inductive coupled plasma-optical emission spectrometry (ICP-oES) at 374 Labs. Rapid preservative effectiveness testing was determined by a reduction in colony forming units (CFU) of test microorganisms at Microchem Laboratory (Round Rock, Texas). Testing confirmed that the compositions were resistant to bacterial growth (by measuring colony forming units (CFUs) per volume in a given amount of time.
  • CFU colony forming units
  • CBD lipid nanoparticles in this example were prepared using a solvent-based method with high pressure homogenization.
  • lipophilic ingredients solid CBD comprising not more than 0.3% THC, medium chain triglyceride, cholesterol, phosphatidylcholine, Vitamin E, oil soluble flavoring, etc.
  • To prepare the lipophilic ingredients approximately 1.3 to 1.5 times the weight of the lipophilic ingredients was added of 100% (200 proof) ethanol. The lipophilic ingredients were dissolved in the ethanol before proceeding.
  • the 20 liter round bottom flask was transferred to a Hei-VAP Industrial Rotary Evaporator (Heidolph Corporation) and the ethanol was removed by evaporation under reduced pressure, elevated temperature, and vessel rotation. When the ethanol was removed, a film of lipid remained on the glass vessel walls. The lipid film was blanketed with nitrogen glass and left at room temperature overnight.
  • Hei-VAP Industrial Rotary Evaporator Heidolph Corporation
  • the volume of lipid slurry can be processed at a pressure of 10,000 - 30,000 PSI such that the material is recirculated back into the unprocessed volume for a period of time until the desired particle size characteristics are achieved.
  • the resulting lipid nanoparticle solution was cooled with continuous stirring for 12 - 24 hours before characterizing and fill-finish. Flavoring in oil form was introduced into the dried lipid film prior to introduction of the aqueous solution. Water soluble flavoring is dissolved into the water for injection prior to introduction into the lipid film.
  • This example discloses stability testing and shelf-life data for some embodiments as prepared in Example 1.
  • the batches prepared in Example 1 were filled into 20 mF amber vials with a child-proof cap affixed with a required removal torque of 7.0 to 9.0 pound force inch.
  • Sealed bottles were stored at 2 - 8°C, 25°C/60% Relative Humidity, 40°C/75% relative humidity, or 50°C and uncontrolled humidity.
  • samples were pulled for characterization on months 0, 1, 2, 3, 6, and 11. Characterization included particle size analysis by dynamic light scattering and CBD concentration by UPLC. Results are show in Figure 3 and 4.
  • shelf-life plots were created in MINITAB Version 17.0 using real-time data only (25°C/60% Relative Humidity).
  • the shelf-life is the period of time in which there is 95% confidence that at least 50% of the response (CBD concentration or particle size) is within the specification limit.
  • Shown in Figure 3 is the shelf-life plot of 4 batches of product as a function of CBD concentration. Over the 11 months where CBD concentration was determined, the response slope of the regression line is not significantly different from zero and no shelf-life can be predicted until a negative slope (e.g., degradation) appears in the data set.
  • Figure 4 shows the shelf-life plot of 4 batches of product as a function of lipid nanoparticle Z- Average size in nanometers.
  • This example discloses representative images of lipid nanoparticles prepared as previously described in Example 1.
  • a sample consistent with the ingredient composition outlined in Batch 1 and 3 was diluted 10 times with water.
  • Three microliters was placed on a thin copper grid (Cu-200CN, Pacific Grid-Tech) that was previously glow-discharged.
  • the sample was loaded into the freezing chamber at low temperature (0 - 5°C) under humidity control (100%).
  • the specimen was rapidly frozen with cryogen, liquid ethane cooled by liquid nitrogen.
  • the prepared dried was mounted on 200kV FEI Talos C200C electron microscope. Microscope images were collected at 45K magnification. Example images are shown in Figure 5.
  • Eipid nanoparticles prepared using the methods of Example 1 afforded several sub-types of particles. Shown in Figure 5 Panel A are characteristic emulsion style particles, Figure 5 Panel B shows lipid nanoparticles containing unilamellar vesicles, also known as small unilamellar vesicles, Figure 5 Panel C shows particles with multilamellar vesicles, Figure 5 Panel D shows combined emulsion and unilamellar vesicles, and Figure 5 Panel D shows irregular particles with lamellar structures and bridges, as well as partial emulsion particles.
  • Figure 5 Panel A are characteristic emulsion style particles
  • Figure 5 Panel B shows lipid nanoparticles containing unilamellar vesicles, also known as small unilamellar vesicles
  • Figure 5 Panel C shows particles with multilamellar vesicles
  • Figure 5 Panel D shows combined emulsion and unilamellar vesicles
  • Figure 5 Panel D shows irregular particles with la
  • these sub-types of particles can be controlled via changes in the ingredients and processing parameters, or combinations of both.
  • concentration of MCT decreases to 0% the proportion of emulsion lipid nanoparticles will decrease and the vesicle sub-type of particles will increase.
  • MCT but possibly includes other oils that are a liquid at room temperature or is a liquid at room temperature when mixed with other lipids.
  • Replacing the liquid oil at room temperature with an oil that is both solid at room temperature and waxy makes a solid lipid nanoparticle product.
  • This type of particle will appear similar to the emulsion lipid particle because both have a dense core.
  • Decreasing the liquid oil and/or increasing the phosphatidylcholine will likely increase the proportion of particles that are mixed or irregular. Decreasing the liquid oil and decreasing the processing pressure will increase the propensity of forming multilamellar vesicles. Decreasing the liquid oil and processing with a larger bore interaction chamber, with or without a reduction in processing pressure will increase the proportion of multilamellar vesicles.
  • CBD isolate containing lipid nanoparticles were prepared according to the methods described in the Manufacturing Process of Example 1.
  • the finished product was mixed with an additional excipient that serves as the lyoprotectant, such as 0%, 5%, 10%, 15%, or 20% of the following alone or in combination lactose, dextrose, trehalose, arginine, glycine, and /or histidine.
  • Excipient was added to the finished product solution and mixed (200 RPM) until dissolved. Additional incubation at room temperature was allowed for material equilibration.
  • a Buchi B290 mini benchtop spray dryer was used to spray dry the CBD lipid nanoparticles to a powder.
  • the inlet temperature of the spray-dryer was set at 60 - 100°C.
  • the aspirator was constant at 35 m 3 /hour and the feed pump varied up to 5 mL/min.
  • Spray drying parameters were varied such that the outlet temperature was maintained at or below 65 °C and yielding a flowable powder.
  • a VirTis Advantage Pro Freeze Dryer was used to lyophilize the CBD lipid nanoparticles to a powder. Samples were placed in 20 mL glass vials with a stopper half seated. Vials were placed on the lyophilizer shelf and equilibrated at 4°C for 6 hours before rapidly freezing at -50°C for 12 hours. Samples were ramped to their lyophilization temperature at a rate of 0.5°C/min. After an additional 30 minutes of equilibration, primary drying commenced with the condenser set at -80°C and chamber pressure set to 100 - 200 mTorr.
  • CBD lipid nanoparticle powders were stored in clear glass vials at 25°C/60% relative humidity for 7 months. Powders were reconstituted and particle size analysis was measured and compared to the original formulation.
  • the original nanoparticle formulation had Z- Average particle size of 125.1 nm (average of three measurements) and the reconstituted powder have a Z-Average particle size of 127.6 nm. Statistical comparison between the two samples resulted in a p-value of 0.115.
  • the polydispersity index of the CBD nanoparticle solution was 0.133 (average of three measurements) and the reconstituted powder had a poly dispersity index of 0.163. Statistical comparison between the two samples resulted in a p-value 0.285.
  • the results demonstrate that the CBD containing lipid nanoparticle can be reconstituted and the same particle size characteristics are preserved in the drying process. Further, since it was 7 months later, the particles are advantageously stable in powder form.
  • CBD lipid nanoparticles were prepared using a solvent free method utilizing a high-shear in-line mixer, followed by high pressure homogenization. All water-soluble formulation ingredients, including water soluble flavoring agents, were dissolved into water for injection at the specified concentrations. Aqueous solutions were heated and filtered prior to further use. Warm aqueous solution was transferred to a mixing vessel with an outlet at the bottom of the container that feeds the inlet of a high-shear in-line mixer (Silverson Verso Mixer). The outlet of high-shear mixer utilizes a tube that returns liquid to the top of the mixing vessel.
  • Method 1 Lipophilic ingredients were accurately weighed into a glass mixing vessel and well dispersed. The lipophilic ingredients were heated with mixing to assist in the dispersion of the materials to form a homogenous lipid slurry. The lipid slurry, including any oil-based flavoring agents, was transferred slowly to the in-line mixing vessel with the mixer activated and emulsified for up to 60 minutes (in a high shear mixer).
  • Method 2 Lipophilic ingredients were accurately weighed onto a weigh boat and then transferred one at a time to the high-shear mixing vessel with the mixer activated. As each ingredient was introduced, 5 to 10 minutes of mixing was allowed before subsequent additions to allow for homogenous dispersion. Once all lipophilic ingredients were added, the lipid slurry was emulsified for up to 60 minutes while maintaining the processing temperature (in a high shear mixer).
  • the dispersion was passed through the microfluidizer 5 times and the resulting Z-Average particle size was measure after each pass (3 measurements per pass).
  • Pass number 0 represents the particle size after high-shear mixing only and had a particle size 385.8 ⁇ 53.1 nm.
  • the resulting particle size was 106.2 ⁇ 1.0 nm and 109.7 ⁇ 1.0 nm.
  • the particle size increased slightly after passes 4 and 5 to 118.0 ⁇ 0.3 nm and 126.2 ⁇ 0.5 nm, respectively.
  • the dispersion was passed through the microfluidizer 5 times and the resulting D90 particle size was measure after each pass (3 measurements per pass).
  • the D90 particle size describes the diameter where 90% of the distribution has a smaller particle size and 10% has a larger particle size.
  • Pass number 0 represents the particle size after high-shear mixing only and had a particle size 2,266.7 ⁇ 1152.4 nm.
  • the resulting particle size decreased to 830.3 ⁇ 1.083.2 nm.
  • the resulting particle size was 185.0 ⁇ 2.0 nm, 191.3 ⁇ 8.4 nm, and 238.7 ⁇ 28.0 nm, respectively.
  • the dispersion was passed through the microfluidizer 5 times and the resulting polydispersity index was measure after each pass (3 measurements per pass).
  • Pass number 0 represents the polydispersity index after high-shear mixing only was 0.754 ⁇ 0.297.
  • the resulting polydispersity index was 0.205 ⁇ 0.006 and 0.172 ⁇ 0.002.
  • the polydispersity index was 0.132 ⁇ 0.013 and 0.151 ⁇ 0.022, respectively.
  • CBD containing lipid nanoparticles were prepared using the solvent based manufacturing process in 100 mL batches with varied lipid concentrations to determine their impact on nanoparticle size distribution and short-term stability. Nanoparticles were aliquoted into 20 mL or greater aliquots in clear glass vessels and stored 2 - 8°C, 25°C with 60% relative humidity, and 40°C with 75% relative humidity. At regular intervals the particle size distribution was determined and Z-Average, polydispersity index, and D90 particle size was recorded. The following table summarizes percent weight of ingredients in the formulations studied.
  • HSPC hydrogenated sunflower phosphatidylcholine
  • MCT medium chain triglyceride
  • CBD cannabidiol
  • CBD containing lipid nanoparticles were smaller with higher total lipid to CBD ratios, including a greater oil phase composition.
  • a similar trend was observed with PDI, a higher total lipid to CBD ratio and higher oil content had a more homogenous particle size distribution.
  • formulations with high lipid and oil content experienced less percent change in particle size and PDI.
  • CBD containing lipid nanoparticles were prepared according to the solvent based manufacturing process using formulation ingredients outlined in batches 2 & 4 in Example 1. Powders of the CBD containing lipid nanoparticles were prepared according to the methods outlined in Example 4.
  • Figure 9A-D Shown in Figure 9A-D are the pharmacokinetic profiles of CBD containing lipid nanoparticles in solution as well the powder formulation filled in gelatin capsules.
  • Figure 9A shows two embodiments as disclosed herein. As demonstrated, the nanoparticle powder had an increased Cmax and the solution had an increased Tmax.
  • Figure 9B shows that the powder formulation in gelatin capsules had a Cmax that was approximately 63% higher than the CBD-oil comparators.
  • the solution formulation had faster Tmax ( ⁇ 4 hours) compared to the CBD-oil comparators, which had a Tmax of greater than 6 hours and close to 8 hours in some samples.
  • Figures 9C and 9D show the CBD lipid nanoparticle solution had detectable concentrations of CBD earlier than the oil-based comparators (within the first hour of the study), as well as reached an apparent Tmax approximately 2 hours earlier than oil-based comparator 3, 4 hours earlier than oil-based comparator 1, and 6 hours earlier than oil-based comparator 2.
  • the CBD lipid nanoparticles reached a higher plasma concentration than comparators 1 and 2.
  • FIG. 10 Shown in Figure 10 is the comparison of the absorption phase of the CBD lipid nanoparticle solutions over the first four hours of the study, and three leading oil-based CBD commercial comparators.
  • measurable levels of CBD were detected in plasma within 30 minutes.
  • the rates of absorption were taken to be the slope of the regression equation.
  • the CBD lipid nanoparticle solution formulation had the shortest half-life of 5.5 ⁇ 5.2 hours and the CBD lipid nanoparticle powder formulation having a half-life of 6.6 ⁇ 2.4 hours (Figure 11).
  • the CBD oil-based comparators had half-lives generally greater than the liquid formulation, of 6.4 ⁇ 3.0, 11.2 ⁇ 9.1, and 7.3 ⁇ 3.8 hours. Table 5.
  • Figure 12 shows AUC or Area Under the Curve information (0 to infinity). See also Table 5.
  • AUC is a pharmacokinetic parameter that reflects a molecule’s total exposure.
  • the CBD lipid nanoparticle solution had an AUC of 557.8 ⁇ 297.5 ng/mL*hr, where the CBD lipid nanoparticle powder had an AUC of 575.9 ⁇ 211.5 ng/mL* hr.
  • both liquid and powder formulations had comparable AUCs.
  • Both oil-based CBD comparators had AUCs that were lower than the Lipid Nanoparticle formulation.
  • Comparator 3 had an AUC of 352.1 ⁇ 216.9 and comparator 1 had an AUC of 393.8 ⁇ 133.0 ng/mL*hr. Indicating the oil-based CBD products had less total exposure than the lipid nanoparticle formulations.
  • the AUC4 - 6 for the CBD lipid nanoparticles and powder was 84.0 ⁇ 64.3 and 119.0 ⁇ 12.9 ng/mL*hr, respectively.
  • the AUCs for this same period of time were 28.2 ⁇ 20.9, 49.2 ⁇ 21.2, and 84.0 ⁇ 64.3 ng/mL*hr for the oil based comparators.
  • the AUCo 10 for the CBD lipid nanoparticles and powder was 129.4 ⁇ 31.5 ng/mL*hr and 191.0 ⁇ 58.1 ng/mL*hr.
  • the AUCs for the CBD oil based comparators were 70.7 ⁇ 36.0, 141.2 ⁇ 45.3, and 141.9 ⁇ 64.5 ng/mL*hr over the same period of time.
  • the higher AUCs during the first 4 hours of the study in the CBD lipid nanoparticle groups demonstrate the rapid absorption compared to the oil-based comparators. Table 6.
  • CBD containing lipid nanoparticles were prepared using the solvent based manufacturing process, however, different concentrations of preservatives were dissolved in the aqueous solution prior to hydration of the lipid film and mixing.
  • Citric acid monohydrate and malic acid was added to Formulation 1 at 6.10 and 5.73 mM, respectively.
  • citric acid was added at 4.88 mM and no malic acid was added.
  • citric acid was added 0.16 mM and no malic acid was added.
  • no citric or malic acid was added. All formulations contained 8.53 mM of potassium sorbate and 8.90 mM of sodium benzoate.
  • Formulations were characterized for pH, particle size distribution, zeta potential, CBD concentration and particle size after storage for 6 or 7 months at 2 - 8°C, 25°C with 60% relative humidity, and 40°C with 75% relative humidity, and a preservative effectiveness challenge.
  • the table below summarizes Formulation initial characterization data.
  • Figure 13 shows the change in CBD lipid nanoparticle size over approximately 6 months at differing solution pH values.
  • Figure 14 shows the change in CBD concentration in lipid nanoparticles over approximately 7 months at differing storing conditions.
  • Solution pH did not impact the stability of the particle size (Figure 13) when measure at regular intervals over approximately 6 months of storage at 25°C with 60% relative humidity. After 7 months of storage at 2 - 8°C, 25°C with 60% relative humidity, and 40°C with 75% relative humidity, the percent CBD remaining was significantly less for pH 4.072 compared to the formulation groups.
  • the formulations were challenged with 5 microorganisms (E.coli, P. aeruginosa, S. aureus, A.brasiliensis, and C. albicans) at 10 7 CFU/mL and the log reduction in colony forming units after incubation for 7 days was calculated.
  • 5 microorganisms E.coli, P. aeruginosa, S. aureus, A.brasiliensis, and C. albicans
  • the minimum require for an effective preservative system is at least a 1.0 log reduction in colony forming units for each organism evaluated after 7 days of incubation.
  • Preservative systems with a pH of 4.459 and 4.07s met the minimum requirements of a preservative system, but solutions with a pH of 5.093 and 6.250 did not.
  • the preservative systems evaluated in this study were more effective at preventing bacterial growth, especially at lower pH, than yeasts and molds.
  • Example 9 Higher concentrations of CBD in the lipid nanoparticle formulation
  • Table 9 The table below summarizes the results of the study as percent change in Z- average particle size and polydispersity index after 100 days of storage at the stated storage temperature. Despite the percent change in particle size parameters at any storage temperature, all were within the product’s specification, indicating that CBD can be incorporated into the formulation beyond 2%. Table 10.
  • Example 10 CBD Containing Lipid Nanoparticles Can Be Filtered
  • CBD containing lipid nanoparticles were prepared using the solvent based method at a 10 liter batch size. Prior to further study, the nanoparticles were characterized for particle size distribution and CBD concentration. To filter the material, the nanoparticle solution was transferred to a pressurized vessel containing a stainless-steel side arm. To the side arm, Pharmed BPT tubing was used to connect the pressurized vessel to a receiving vessel, with a 3M betafine filter in-line. To filter the nanoparticle solution, nitrogen gas was filled into the pressurized vessel to displace the solution forcing it through the filter and into the receiving vessel. Two 3M betafine filters were evaluated in this study, a 0.2 micron and 0.65 micron polypropylene filter. After filtration, the particle size distribution and CBD concentration was measured again and compared to the starting measurements. All measurements were performed in triplicate.
  • Example 11 Resulting Particle Size Distribution By Operating Pressure And Pass Number
  • CBD containing lipid nanoparticles were prepared by the solvent based manufacturing process in batch sizes of 100 mL.
  • the purpose of the first part of the study was to determine the impact of pass number on the initial particle size distribution and any changes after 6 months of storage at 25°C with 60% relative humidity.
  • the full volume of lipid slurry was microfluidized 10 times with a sample collection after each volume for analysis. Shown below in Figure 15 is the Z-Average and D90 particle sizes. After 1 pass through the microfluidizer, the Z-Average was below 200 nm but the D90 particle size was 1.0 micron. After 2 passes through the microfluidizer both the Z-Average and D90 were below 200 nm.
  • Example 12 CBD Containing Lipid Nanoparticles Prepared With Several CBD Isolates [00324] CBD containing lipid nanoparticles were prepared using the solvent based manufacturing process or the solvent free, high shear mixing process in 100 mL batches. Lipid nanoparticles were prepared with CBD isolate from different manufacturers, all of which had greater than 99% CBD purity and no detectable THC. Nanoparticles were prepared at 20 mg/mL and the final concentration was verified by UHPLC. All preparations had a Z-average particle size between 85.4 nm and 105.6 nm, a D90 particle size of 113.0 nm to 153.2 nm, and a polydispersity index of 0.105 to 0.169.
  • Example 13 CBD Containing Lipid Nanoparticles Prepared With Full Or Broad Spectrum CBD Material
  • CBD containing lipid nanoparticles were prepared by the solvent based and/or solvent free manufacturing process in 0.1 liter batches.
  • the CBD origin was from a full spectrum or broad spectrum hemp extract where the CBD content varied from 44.25% to 86.6%.
  • the THC content was below 0.3% or not detectable. All formulations were prepared to a final concentration of 20 mg/mL CBD and confirmed by UHPLC. Modifications to the remaining lipids in the formulations were made to accommodate the lower concentration of CBD in the full/broad spectrum hemp extracts.
  • All formulations had a Z-average particle size between 94.88 nm and 178.0 nm, a D90 particle size between 132.0 nm and 265.0 nm, and a polydispersity index of 0.100 to 0.221.
  • the resulting particle size attributes were not different from those prepared with CBD isolate, indicating the broad or full spectrum CBD can be exchanged with CBD isolate in the lipid nanoparticle formulation.
  • Example 14 Lipid Nanoparticles Prepared with CBG Isolate, CBN Distillate, and CBDa Oil
  • Lipid nanoparticles were prepared with other commercially available cannabinoids using the solvent based manufacturing process and characterized for particle size distribution.
  • Global cannabinoids CBG isolate had 93.34% CBG by weight, with no other cannabinoids detected (based on Manufacturer’s COA).
  • the Z-av erage particle size was 105.6 nm, the D90 particle size was 241.0 nm, and the polydispersity index was 0.206.
  • Lipid nanoparticles were prepared with CBN distillate from global cannabinoids. The CBN distillate was 80.5% CBN by weight, contained 3.1% CBC by weight, but no other cannabinoids were detectable (based on Manufacturer’s COA).
  • the Z- average particle size was 99.59 nm
  • the D90 particle size was 139.0 nm
  • the polydispersity index was 0.138.
  • Lipid nanoparticles were also prepared using a dilute CBDa oil (Myriam’s Hope, Nevada) with not modification to the formulation lipid ratios (results not shown). The results of the CBG and CBN nanoparticles are summarized in the table below.
  • Example 15 Phytosterol Alternatives To Cholesterol Used To Prepare CBD Containing Lipid Nanoparticles
  • CBD lipid nanoparticle formulations were prepared using the solvent based manufacturing process in 0.1 liter batches.
  • formulations were prepared with different phytosterols as alternatives to cholesterol.
  • the physterosterols were purchased from BASF corporation and named Vegapure 867 GN, Vegapure FS, and Vegapure 95DS.
  • the phytosterol replaced cholesterol in the formulation at the same weight percent, no additional modifications were made to the formulation, no cholesterol was added.
  • the table below summarizes the initial particle size measurements using the three phytosterol alternatives to cholesterol.
  • the Vegapure 867 GN had a Z-average particle size of 85.1 nm and PDI of 0.152
  • the Vegapure FS had a Z-average particle size of 87.6 nm and PDI of 0.168
  • the Vegapure 95 DS had a particle size of 130.7 nm and PDI of 0.400.
  • CBD lipid nanoparticles were prepared using the solvent based manufacturing process at 0.1 -liter batches.
  • the medium chain triglycerides (MCT) were replaced with alternatives available from ABITEC Corporation.
  • Captex 8000 NF is triglyceride of caprylic acid
  • Captex GTO is a triglyceride of oleic acid
  • Captex 1000 is a triglyceride of capric acid.
  • the Captex triglycerides replaced the MCT in the weight percents stated in the table below. The table also summarizes the initial particle size and polydispersity index. Table 16a.
  • CBD lipid nanoparticles were prepared using the solvent based manufacturing process at 0.1 liter batches.
  • the medium chain triglycerides (MCT) were replaced with alternative non-aqueous liquids including omega-3 fatty acids (Tonalin and Pronova Pure® 46:38), glyceryl monooleate, conjugated linoleic acid, and alpha glycerylphosphorylcholine (alpha-GPC).
  • the ingredients replaced MCT with an equivalent weight (10%) as presented in the original formulation.
  • the table below summarizes the formulations and the initial particle size measurements. Table 16b.
  • a composition for the delivery of CBD was prepared using the following method. To prepare the composition, CBD (2.0 g) was dissolved in medium chain triglyceride (9.3 g) with mixing. To this solution was added, cholesterol (1.0 g) and phosphatidylcholine (10.0 g). Vitamin E was added (0.05 g) with stirring and to act as an antioxidant in the oil phase. At that time, malic acid (0.085 g), citric acid (0.085 mg), potassium sorbate (0.1 g), sodium benzoate (0.1 g), and Monk Fruit Extract (0.09 g) was added to water (76.07 g) with mixing. The aqueous phase was added to the oil phase with mixing.
  • the oil-in-water emulsion was processed to a nanoparticle (about 20 - 500 nm) by successively passing the solution through microfluidizer (5 times at 30,000 PSI) at a temperature of at least 65 °C.
  • the microfluidizer contained an interaction chamber consisting of 50 to 70 um pore sizes.
  • CBD isolate 2.0 g
  • medium chain triglyceride 9.3 g
  • cholesterol 1.0 g
  • phosphatidylcholine 10.0 g
  • Vitamin E 0.05 g
  • An oil-in-water emulsion was prepared by suspending the dried composition with 76.07 g of warm water containing malic acid (0.085 g), citric acid (0.085 mg), potassium sorbate (0.1 g), sodium benzoate (0.1 g), and Monk Fruit extract (0.09 g).
  • the oil-in-water emulsion was processed to a nanoparticle (20 - 500 nm) by successively passing the solution through microfluidizer 5 times at 30,000 PSI at a temperature of at least 75°C.
  • the microfluidizer contained an interaction chamber consisting of 50 to 70 um pore sizes.
  • Example 19 Testing of an Embodiment of the Composition [00336] A 5 Liter manufacturing batch was analyzed by high pressure liquid chromatography (HPLC) to measure cannabinoids present in the sample. The results were as shown in the following table:
  • Noopept N-phenylacetyl-L-prolyglygice ethyl ester
  • Formulations 1 - 5 were placed on a 90 day stability study at 2 - 8°C, 25°C with 60% relative humidity, and 40°C with 75% relative humidity. The initial particle size measurements and measurements after 90 days at each stability temperature are shown in the table below. Table 21.
  • Noopept lipid nanoparticle formulations may be modified further by coincorporating a cannabinoid, such as CBD, CBG, CBN, or CBDa into the formulation.
  • the formulation may be stored as a liquid or dried to a powder as outlined in Example 4.
  • Lipid nanoparticle formulations containing melatonin alone and melatonin and CBD were prepared using the solvent based manufacturing process. Melatonin alone or melatonin and CBD were, along with the other lipid ingredients, partially to completely dissolved in ethanol prior to drying to a film. The film was blanketed in nitrogen gas and stored for a period of 12 to 24 hours at 4°C prior to processing. Solid lipid films were hydrated with warm water and mixed for 30 minutes to form a lipid slurry before being microfluidized. All formulations were prepared in 100 mF batches. The table below summarizes the formulations made in this example.
  • CBD and melatonin lipid nanoparticles were spray dried to a powder after the addition of trehalose to the liquid feed solution. Formulations were spray dried as outlined in Example 4. Prior to forming a powder, the initial particle size distribution was measured for
  • Formulations 1 - 5 (melatonin only) and summarized in the table below. Powder formulations were sieved successively through 75 to 34 microns. Residual moisture for the powders was measured to be less than 6% for all formulations.
  • Example 22 Lipid Nanoparticle Powder Formulations Of CBD, Melatonin, and GABA
  • the following lipid nanoparticle formulations are designed to promote sleep.
  • the formulations were prepared using the solvent based manufacturing process in 200 mL batches. All lipids, CBD, and melatonin was dissolved in ethanol and dried to a film. The film was hydrated with a warm media containing up to 1.052 mg/mL each of sodium benzoate and potassium sorbate, and up to 0.622 mg/mL each of citric acid monohydrate and malic acid.
  • GABA gamma-aminobutyric acid
  • Example 23 Stability of CBD Lipid Nanoparticles in Simulated Gastric and Intestinal Fluids
  • the stability of CBD Lipid Nanoparticles through the digestive process was simulated by measuring the particle size distribution in simulated gastric fluid after 2 hours, followed by dilution and incubation in simulated intestinal fluid after 4 hours.
  • the CBD lipid nanoparticles were prepared using the solvent based manufacturing process at the 100 mL scale.
  • Simulated gastric fluid was prepared by dissolving/dispersing 1 gram of sodium chloride (CAS 7647-14-5), 21.5 mg of sodium taurocholate (CAS 345909-26-4), 6.5 mg of lecithin (CAS 8002-43-5), and sufficient hydrochloric acid (CAS 7647-01-0) into purified water (QS 500 mL) to achieve a final pH of 1.6.
  • Simulated intestinal fluid was prepared by dissolving/dispersing 1 gram of sodium chloride (CAS 7647-14-5), 806.5 mg of sodium taurocholate (CAS 345909-26-4), 64.4 mg of lecithin (CAS 8002-43-5), 1.1 grams of maleic acid (CAS 110-16-7), and 696 mg of sodium hydroxide (CAS 1310-73-2) in purified water (QS 500 mL). The pH was adjusted to 6.5 as needed. Simulated solutions were used immediately or stored at 4°C for no longer than 1 month.
  • the conical tube containing the simulate fluid and sample was placed inside a 37°C shaker incubator for 2 hours. At the end of the first incubation a sample was taken for particle size analysis. Immediately, the Float-A-Lyzer is placed in a new conical tube containing 20 mL of simulated intestinal fluid and returned to the 37°C shaker incubator for 4 hours. At the end of the second incubation a sample was taken for particle size analysis. The total time of the experiment was 6 hours. Three commercially available, oil-based CBD products were analyzed similarly. All samples were measured in triplicate.
  • FIG. 19A and 19B show the change in particle size and poly dispersity index over the incubation period in simulated gastric and intestinal fluid.
  • the CBD lipid nanoparticles experienced no change in particle size and a modest increase of PDI during the full incubation period.
  • All the commercial oil-based CBD products experienced fluctuations in particle size and PDI during the incubation in simulated gastric and/or intestinal fluids, indicating an instability in the formulation during the digestive process.
  • Example 24 Preparation of CBD Lipid Nanoparticles With Oil Based, Less Pure Phospholipids
  • CBD containing lipid nanoparticles were prepared using the solvent based manufacturing process in 0.1 liter batches.
  • Lipid nanoparticles were prepared with oil based phospholipids and compared to the 99.0% pure phosphatidylcholine (H100-3).
  • the compositions of the oil based phospholipids are provided in the table below under composition (information taken from manufacturer’s COA), along with the initial particle size distribution measurements.
  • Example 25 Examples of Sweeteners.
  • CBD lipid nanoparticles were prepared using the solvent based manufacturing process at the 100 mL batch size. Dried lipid films were hydrated with a hydration media containing up to 1.052 mg/mL each of sodium benzoate and potassium sorbate, and up to 0.622 mg/mL each of citric acid monohydrate and malic acid as preservatives. A sweetener (0.09% w/w) was dissolved in the hydration media prior to adding to the dried film based on the formulations table below, no additional flavoring agent was added to the formulation. A day after processing the formulations were screened for initial particle size distribution (shown in the table below). Initial particle size measurements indicate that all sweeteners evaluated from Monkfruit Corporation, GLG Corporation, and Tate and Lyle are compatible with the CBD lipid nanoparticle formulation.
  • Example 26 Stability of CBD Lipid Nanoparticles in Hot and Cold Coffee Products
  • CBD lipid nanoparticles was dispersed in coffee beverages at a concentration of 10 mg CBD per 8 ounce coffee beverage.
  • a hot coffee beverage was prepared using the pour over technique, the resulting liquid was 130°F at the time the CBD lipid nanoparticles were introduced.
  • CBD nanoparticles were also dispersed in a nitro cold brew coffee (PARKS COFFEE), the coffee beverage was at 2 - 8°C at the time the nanoparticles were introduced.
  • PARKS COFFEE nitro cold brew coffee
  • the coffee beverage was at 2 - 8°C at the time the nanoparticles were introduced.
  • the coffee was diluted for particle size measurement.
  • the initial particle size measurement in each solution was compared to the particle size after 30 minutes of storage in two coffee beverages. As shown in the Figure 21, the particle size only increased by 11.3% and 6.5% in cold and hot coffee beverages over 30 minutes, respectively, indicating the CBD lipid nanoparticles are stable in coffee beverages.
  • Lipid nanoparticles were prepared according to Example 1 with slight modifications. Briefly, cannabidiol (40 or 20 mg/mL), hydrogenated sunflower phosphatidyl choline (100 mg/mL; HSPC), MCT (95 mg/mL) and plant sterols (10 mg/mL; Vegapure) were dissolved into a minimal amount of ethanol. Subsequently the ethanol was removed leaving a thin film of product on the wall of the round bottom, glass vessel. In a separate vessel, potassium sorbate (1 mg/mL), sodium benzoate (1 mg/mL), and citric acid (1 mg/mL) were dissolved into 99.7 grams of purified water with mixing.
  • the aqueous solution was warmed to 70°C, then 78 grams was used to hydrate the thin lipid film in the round bottom flask.
  • a pre-emulsion was formed with the lipid film and aqueous solution by mixing at 70°C for an additional 30 minutes.
  • the pre-emulsion was then processed through a microfluidizer at 30,000 PSI for 5 discreet passes to achieve the desired particle size.
  • GT Kombucha beverages were purchased at WHOLE FOODS. Beverages were inverted several times to achieve a homogenous dispersion of ingredients within the glass bottles. The caps were gently opened so that the beverages could degas.
  • For the beverage containing 20 mcg/mL of CBD 236.6 uL of 40 mg/mL of CBD containing lipid nanoparticles was added directly to the 473 mL of kombucha using a 1.0 mL pipettor. This was equivalent to 9.5 mg of CBD and 48.6 mg of total lipids and vitamin E in a -474 mL volume. If an equivalent amount CBD were added as a powder, -70 to 139 mg of powder would be added, depending on the concentration of CBD in the powder.
  • Example 28 Viscosity Measurement of an Embodiment
  • the viscosity of the CBD lipid nanoparticles was measured using a low volume adapter attached to a LV-DV-II+ Brookfield viscometer (Brookfield, Middleboro, MA). The viscosity was determined using 16 mL of solution at 26°C and a spindle speed of 60 RPM, measured over 3 minutes. The viscosity of the CBD lipid nanoparticle solution was determined to be 5.096 Cp.
  • a composition for the delivery of synthetic CBD was prepared using the methods similar to those disclosed in Example 1. Particle size and zeta potential of liquid was measured on a Malvern ZS90 Zetasizer (Malvern, UK). The liquid product was diluted at least 50 times in purified water and the equivalent of 1 mg of CBD in a powder form was dissolved in 1 mL of purified water for measurements. Cannabinoids concentration was measured by ultra high-pressure liquid chromatography (UHPLC). The mean particle size was found to be 97.4 nm with a D90 of 146.7 nm. The PDI was 0.168 and the nanoparticles had a zeta potential of +4.2 mV. The synthetic CBD concentration was measured to be at 1.96%. Results are summarized in the table below.
  • a composition for the delivery of synthetic CBDV was prepared using the methods similar to those disclosed in Example 1.
  • the resulting particle size and zeta potential were determined using a Malvern ZetaSizer and CBDV concentration was determined using a UPLC.
  • the PDI was 0.140 and the nanoparticles had a zeta potential of +5.04 mV.
  • the synthetic CBDV concentration was measured to be at 1.801%. Results are summarized in the table below. Table 29.
  • a composition for the delivery of synthetic CBG was prepared using methods similar to those disclosed in Example 1.
  • the resulting particle size and zeta potential were determined using a Malvern ZetaSizer and CBG concentration was determined using a UPLC.
  • the mean particle size was found to be 95.7 nm with a D90 of 132.0 nm.
  • the PDI was 0.103 and the nanoparticles had a zeta potential of +5.08 mV.
  • the synthetic CBG concentration was measured to be at 1.664%. Results are summarized in the table below. Table 30.
  • a composition for the delivery of CBT distillate was prepared using methods similar to those in Example 1.
  • the resulting particle size and zeta potential were determined using a Malvern ZetaSizer and CBT concentration was not determined.
  • the mean particle size was found to be 80.4 nm with a D90 of 104.3 nm.
  • the PDI was 0.144 and the nanoparticles had a zeta potential of +6.81 mV. Results are summarized in the table below. Table 31.
  • Lipid nanoparticles containing 4% CBD (40 mg/mL) were prepared by forming an oil-in-water emulsion from a dried lipid composition and hydration media containing citric acid, sodium benzoate, potassium sorbate, and Monk Fruit Extract, as previously mentioned. An acceptable particle size was accomplished by high pressure homogenization.
  • the CBD nanoparticle solution was filled into a 7 mL vial affixed with a fine mist pump sprayer. Approximately 1.6 grams of CBD nanoparticles were evenly sprayed onto ⁇ 2 grams of finely ground hemp flower to fortify the hemp with CBD. After coating the hemp with the liquid, the hemp was cured in a circulating drying. A cannabinoids profile of the hemp flower was developed before and after fortification with CBD nanoparticles by UPLC.
  • CBD concentration in the hemp flower went from 2.148% to 4.138% following fortification with CBD nanoparticles. While CBD concentration increased with fortification, the remaining cannabinoids decreased in concentration.
  • A9-THC in the hemp flower exceeded the limits to be considered hemp before fortification; however, after fortification the A9-THC concentration dropped below the 0.3% limit. Fortification of hemp flower with CBD nanoparticles proves to be a viable approach for remediation of hemp that exceeds permissible limits of A9-THC.
  • Example 34 Preparing Lipid Nanoparticles Containing Cannabinoids and Alpha-Pinene
  • a composition for the delivery of hemp distillate with alpha-pinene terpene added was prepared using procedures similar to Example 1.
  • the hemp distillate was determined to contain CBD, CBG, CBN, CBC, and CBDV. When all ingredients were dissolved, the solvent was removed to form a dried composition.
  • the resulting particle size and zeta potential were determined using a Malvern ZetaSizer and cannabinoid concentrations were determined by UPLC. Terpene concentrations were determined by GC-FID.
  • the cannabinoid profile was measured by UPLC and results shown in the table below.
  • the CBD concentration was found to 1.229% and minor cannabinoids of CBG, CBN, CBC, and CBDV were also detectable.
  • terpenes were detectable in the formulation; however, the predominant terpene was alpha-pinene, the terpene intentionally added to the formulation.
  • the mean particle size of the formulation was found to be 86.5 nm with a D90 of 114.0 nm.
  • the PDI was 0.082 and the nanoparticles had a zeta potential of +4.02 mV.
  • Example 35 Compositions That Survive Pasteurization
  • Lipid nanoparticles containing 4% CBD were prepared by forming an oil-in-water emulsion from a dried lipid composition and hydration media (resulting in a composition similar to that prepared in Example 1).
  • a manufacturing setting i.e. beverage manufacturing
  • 200 mL of deionized water was heated to a critical temperature and allowed to stabilize.
  • encapsulated CBD was introduced to the water such that the CBD was at a final concentration of 0.1 mg/mL.
  • the diluted encapsulated CBD was held for the specific time to achieve pasteurization. After the required time has lapsed, the solution was cooled to room temperature (20 - 25°C). The following pasteurization conditions were evaluated.
  • a non-pasteurized solution was prepared as a control.
  • a sample of the solution was collected after each condition cooled to room temperature and again after 1 week of storage at room temperature.
  • Samples were evaluated for CBD concentration by UPLC and particle size analysis by dynamic light scattering (Z-average). No significant differences were detected between pasteurization conditions or 1 week after pasteurization with CBD concentration, particle size increased slightly after pasteurization. Table 36.
  • Example 36 Compositions That Survive Ozonation
  • Lipid nanoparticles containing 4% CBD were prepared by forming an oil-in-water emulsion from a dried lipid composition and hydration media (resulting in a composition similar to that prepared in Example 1).
  • encapsulated CBD was diluted to a final CBD concentration of 0.2 mg/mL in 500 mL of deionized water.
  • An Ozone Air & Water Purifier was used to ozonate the encapsulated CBD solution for up to 30 minutes. At 10- minute intervals (up to 30 minutes) a sample of the solution was collected for CBD concentration by UPLC and particle size analysis (Z-average) by dynamic light scattering.
  • Ozonated solutions were stored at room temperature for 1 week and analyzed again for CBD concentration and particle size analysis.
  • a non-ozonated solution was prepared as a control. No significant differences were detected between ozonation conditions or 1 week after ozonation with CBD concentration, particle size increased modestly after ozonation.
  • Example 37 Compositions That Survive Ultraviolet (UV) Treatment
  • Lipid nanoparticles containing 4% CBD were prepared by forming an oil-in-water emulsion from a dried lipid composition and hydration media (resulting in a composition similar to Example 1).
  • encapsulated CBD was diluted to a final CBD concentration of 0.2 mg/mL in 500 mL of deionized water.
  • a UV source was used to UV treat 0.5 liters of encapsulated CBD solution for either 1 cycle or 10 cycles of treatment with mechanical stirring. After each cycle of treatment a sample of the solution was collected for CBD concentration by UPLC. UV treated solutions were stored at room temperature for 1 week and analyzed again for CBD concentration. A non-UV treated sample was collected as a control. No significant differences were detected between UV treatment cycles or 1 week after UV treatment with CBD concentration.
  • Example 38 Preparing a Two Ounce Ready-To-Drink (RTD) Beverage For Immunity Support
  • Lipid nanoparticles containing 2% CBD (20 mg/mL) are prepared by forming an oil-in-water emulsion using methods similar to those disclosed in Example 1.
  • the 2 ounce RTD kombucha beverage for immunity support is constructed by dissolving 125 mcg vitamin D3 (as cholecalciferol), 25 mg of magnesium (as magnesium chloride), and 20 mg of zinc (as zinc gluconate) into 58 mL of the kombucha drink.
  • One mL of the 2% encapsulated CBD solution is added to bring the total volume to 59 mL and CBD concentration to 0.339 mg/mL.
  • Monk Fruit extract and flavor are added as needed.
  • Lipid nanoparticles containing 2% CBD (20 mg/mL) are prepared by forming an oil-in-water emulsion using methods similar to those disclosed in Example 1.
  • the 2 ounce RTD kombucha beverage for calm sensation is constructed by dissolving 200 mg L-Theanine into 57.5 mL of the kombucha drink.
  • One and a half mL of the 2% encapsulated CBD solution is added to bring the total volume to 59 mL and CBD concentration to 0.508 mg/mL.
  • Monk Fruit extract and flavor are added as needed.
  • Example 40 Preparing a Two Ounce Ready-To-Drink (RTD) Beverage For Energy Support
  • Lipid nanoparticles containing 2% CBC (20 mg/mL) and 0.5% THCV (5 mg/mL) are prepared by forming an oil-in-water emulsion using methods similar to those disclosed in Example 1.
  • the 2 ounce RTD kombucha beverage for immunity support was constructed by dissolving 40 mg niacin, 4 mg of vitamin B6, 6 mcg of vitamin B 12, and 100 mg of L- tyrosine into 58 mL of the kombucha drink.
  • One mL of the 2% encapsulated CBC/0.5% THCV solution is added to bring the total volume to 59 mL and CBC concentration to 0.339 mg/mL and 0.085 mg/mL THCV.
  • Monk Fruit extract and flavor are added as needed.
  • Formulations were prepared using ingredient profiles and techniques as disclosed herein in Example 27, with the concentrations of the CBD and Vitamin D3 as defined below. The impact of several quality attributes of the formulation on particle size, vitamin D3 and CBD concentration, and product stability in fermented beverages were determined.
  • Fermented beverages (kombucha) from brands HEALTH- ADE (Watermelon, Tropical Punch, and Passion Fruit Tangerine), GT’s Brand (Matcha Vanilla, Mystic Mango, and Guava Left), and ORGANIC BREW DR (Superberry, Love, and Ginger Lemon) were purchased from a local grocery store.
  • the CBD isolate used comprised not more than 0.3 THC by weight per weight (w/w).
  • phosphatidylcholine Two grades of phosphatidylcholine was used, the H100-3 grade included over 97% phosphatidylcholine, were the H20 grade consisted of 27.69% phosphatidylcholine, 23.68% phosphatidylinositol, 11.47% phospatidylethanolamine, and the rest of the composition consisted of other phospholipids and fatty acids.
  • Particle size and zeta potential of the liquid formulations was measured on a Malvern ZS90 (Malvern, UK). The liquid product was diluted at least 100 times in purified water for measurement. Products were measured in low-volume, disposable cuvettes and zeta cassettes.
  • Cannabinoids and vitamin D3, related substances, and identity (retention time) were measured by high-pressure liquid chromatography at Sante Labs (Austin, TX) or Micro Quality Labs (Pasadena, CA). Ethanol content was measured by gas chromatography (GC) and microbiology (total aerobic plate count, yeast and molds, and coliforms) using media plates was performed at Sante Labs.
  • GC gas chromatography
  • microbiology total aerobic plate count, yeast and molds, and coliforms
  • the full volume of the lipid emulsion was processed through a microfluidizer (Microfluidics Corporation) up to 5 times at a processing pressure up to 30,000 PSI.
  • the volume of processed lipid emulsion can be recirculated back into the unprocessed volume for a period of time until the desired particle size characteristics are achieved.
  • the resulting lipid particle solution was cooled with continuous stirring for 12 - 24 hours before being used in further processing.
  • Lipid particles containing vitamin D3 were prepared similarly, except where CBD is dissolved into the room temperature liquid lipids, vitamin D3 was instead.
  • Lipid nanoparticles were prepared with either H100-3 or H20 phosphatidylcholine.
  • Both encapsulated products had similar D90 particle sizes of 123 nm and 146 nm for CBD and vitamin D3, respectively. Both had homogenous particle size distributions as seen by the polydispersity index between 0.131 and 0.151. Both had modestly positive surface charges between +6.920 and +7.965 mV. The concentrations reported in the table above were used to dilute to a final concentration in the kombucha fermented beverage.
  • All fermented beverages had a recommended storage condition of 2 - 8 °C and were stored under these conditions for all stability studies.
  • the fermented beverages had an acidic pH and was in the range of 2.893 to 4.002.
  • All beverages reported a sugar content on the product label, which ranged from 11 to 20 grams.
  • Characteristic to fermented beverages the ethanol concentration was measured and found to range from less the detection limit and up to 5,537.99 ppm. Not shown in, microbiology measurement was taken on each product prior to starting additional experiments. Each product was found to contain total aerobic plate counts.
  • Encapsulated CBD added to the three flavors of GT’s brand kombucha fermented beverage are shown in Figure 23.
  • Encapsulated CBD measured at each of the time points was between 97 and 110% of the starting concentration. No other cannabinoids were detected throughout the 6 months of storage at 2 - 8°C, including delta-9 THC.
  • Encapsulated CBD added to the three flavors of ORGANIC BREW DR’s brand kombucha fermented beverage are shown in Figure 24.
  • Encapsulated CBD measured at each of the time points was between 82 and 111% of the starting concentration. No other cannabinoids were detected throughout the 6 months of storage at 2 - 8°C, including delta-9 THC.
  • the variability in CBD measurements observed in the Eove flavor were likely due to the homogeneity of the sample and natural sedimentation that occurs in fermented beverage products.
  • Encapsulated CBD added to the three flavors of HEALTH- ADE brand kombucha fermented beverage are shown in Figure 25.
  • Encapsulated CBD measured at each of the time points was between 92 and 112% of the starting concentration. No other cannabinoids were detected throughout the 6 months of storage at 2 - 8°C, including delta-9 THC.
  • kombucha fermented beverages contain particulate ingredients that naturally sediment.
  • the presence of the particulates makes measuring the particle size of the encapsulated CBD within the beverage difficult by dynamic light scattering. Therefore, no particle size measurements are reported during storage in the fermented beverage.
  • Encapsulated vitamin D3 added to the watermelon flavor of HEALTH-ADE’ s brand kombucha fermented beverage are shown in Figure 26. After 6 months of storage at 2 - 8°C the percent remaining of vitamin D3 was at 96% of the starting concentration. In other words, a loss of approximately 4% of the starting concentration of vitamin D3 was measured under these storage conditions.
  • Encapsulated vitamin D3 added to the love flavor of ORGANIC BREW DR’s brand kombucha fermented beverage are shown in Figure 27. After 90 days of storage at 2 - 8°C the percent remaining of vitamin D3 was at 95.6% of the starting concentration. In other words, a loss of approximately 4.4% of the starting concentration of vitamin D3 was measured under these storage conditions.
  • the appearance of the kombucha fermented beverages was unchanged from the start of the study compared to each time point throughout the 6 months of storage at 2 - 8°C.
  • Kombucha fermented beverages experience a natural sedimentation of particulate ingredients over time and this was observed in samples containing the encapsulated vitamin D3 as well.
  • the encapsulated product added to the beverage was not found to phase separate or aggregate within the beverage throughout the 90 days of storage at 2 - 8°C.
  • Kombucha fermented beverages contain particulate ingredients that naturally sediment. The presence of the particulates makes measuring the particle size of the encapsulated vitamin D3 within the beverage difficult by dynamic light scattering. Therefore, no particle size measurements are reported during storage in the fermented beverage.
  • the solid line in Figure 28 represents the fitted regression line of the data set, where the dotted line represents the lower 95% confidence band for the data set.
  • the shelflife of the product is determined when the confidence band crosses the lower specification limit. In Figure 28, the shelf-life could not be determined because the confidence band does not cross the lower specification limit within the 6 months of storage at 2 - 8°C. This indicates that the encapsulated product will remain stable during the anticipated shelf-life of the kombucha fermented beverage.
  • a composition for the delivery of Piper methysticum extract was prepared using the following method.
  • the extract is expected to be composed of alkaloids and kavalactones, such as pipermethystine, dihydrokavain, kavain, desmethoxyyangonin, dihydromethysticin, yangonin, and methysticin.
  • Piper methysticum extract is added along with medium chain triglycerides, Vegapure 867 GN, phosphatidylcholine, and Vitamin E. When all ingredients were dissolved, the solvent was removed to form a dried composition.
  • the aqueous phase was formed by dissolving citric acid, potassium sorbate, sodium benzoate, and Monk Fruit extract into grams of warm water.
  • the aqueous phase was added to the dried lipid composition with mixing to form an oil-in-water emulsion.
  • the particle size was reduced to 20 - 500 nm by high pressure homogenization at 30,000 PSI at a temperature of at least 55°C.
  • the high-pressure homogenizer contained an interaction chamber consisting of 50 to 70 micrometer pore size. This composition can be added to a kombucha beverage where the Piper methysticum extract maintains high levels of activity over time.
  • a composition for the delivery of Sceletium (kanna) extract was prepared using the following method.
  • the extract is expected to be composed of alkaloids, such as, but not limited to, joubertiamine dehydrojoubertiamine dihydrojoubertiamine joubertinamine, O- methyldehydrojoubertiamine, O- methyljouberiamine, O-methyldihydrojoubertiamine, 3’- methoxy-4’-o-methyl joubertiamine, 4-(3,4-dimehoxyphenyl)-4-[2- acetylmethylamino)ethyl]cyclohexanone, 4-(3-methoxy-4- hydroxy-phenyl)-4-[2- (aceylmethylamino)ethyl]cyclohexadienone, sceletium alkaloid A4, touruosamine, N- formyltortuosamine, N-acetyltortuosamine.
  • Sceletium extract is added along with medium chain triglycerides, Vegapure 867 GN, phosphatidylcholine, and Vitamin E. When all ingredients were dissolved, the solvent was removed to form a dried composition.
  • the aqueous phase was formed by dissolving citric acid, potassium sorbate, sodium benzoate, and Monk Fruit extract into grams of warm water.
  • the aqueous phase was added to the dried lipid composition with mixing to form an oil-in-water emulsion.
  • the particle size was reduced to 20 - 500 nm by high pressure homogenization.
  • This composition can be added to a kombucha beverage where the Sceletium (kanna) extract maintains high levels of activity over time.
  • a composition for the delivery of CBN isolate was prepared using the following method. To a minimal amount of ethanol, medium chain triglycerides, Vegapure 867 GN, phosphatidylcholine, and Vitamin E are added and mixed to dissolve. When dissolved, the solvent was removed to form a dried composition. An aqueous phase was formed by dissolving citric acid, potassium sorbate, sodium benzoate, and Monk Fruit extract into grams of warm water. The aqueous phase was added to the dried lipid composition with mixing to form an oil-in-water emulsion. The particle size was reduced to 20 - 500 nm by high pressure homogenization. The result is an empty lipid nanoparticle with no encapsulated ingredient.
  • CBN isolate is added to the empty lipid nanoparticle composition and mixed to allow the hydrophobic CBN ingredient intercalate into the lipophilic interior of the nanoparticle.
  • heating and high shear mixing may be employed to promote intercalation.
  • the result is a CBN loaded lipid nanoparticle with a particle size of 20 - 500 nm. With storage, there is no sedimentation expected of the particles or CBN isolate.
  • This composition can be added to a kombucha beverage where the CBN maintains high levels of activity over time.
  • Lipid nanoparticles containing a kratom extract were manufactured using methodologies and ingredients comparable to those in Example 1.
  • the kratom extract used to make the lipid nanoparticle was found to contain greater than 70% total alkaloids with mitragynine, paynantheine, speciogynine, and speciocilliatine alkaloids being detectable.
  • the formulation was targeting a mitragynine concentration of 11.0 mg/mL.
  • Kratom alkaloids were measured using UPLC and particle size was measured using dynamic light scattering on Malvern Zetasizer ZS90. The same kratom alkaloids present in the kratom extract were also present in the lipid nanoparticle formulation. The measured concentration of alkaloids present in the formulation is shown in the table below. The Z-average particle size was measured to be 98.93 nm and had a PDI of 0.227. Particle size data is shown in the table below. These compositions can be added to a kombucha beverage where the extracts maintain high levels of activity over time.
  • the first group is treated with a mushroom extract (psylocibin) containing lipid-based particle composition in kombucha as disclosed herein orally.
  • the second group is treated with kava extract containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • the third group is treated with kanna extract containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • the fourth group is treated with kratom extracts containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • Groups fifth through eight are treated with kratom, kava, kanna, and mushroom biomass in kombucha, respectively.
  • the ninth group of patients is treated with a placebo orally.
  • the patients in the groups one through four report less feelings of nervousness, less feelings of restlessness, less feelings of impending danger, panic or doom, less trouble concentrating, less trouble sleeping.
  • After oral ingestion the patients in groups one through four have lower heart rates and less trembling than those in groups five through eight. The results show statistically significant improvements in the groups one through four relative to either groups five through eight or the ninth group.
  • the first group is treated with a kratom containing lipid-based particle composition in kombucha as disclosed herein orally.
  • the second group is treated with kava extract containing lipid-based particle composition in kombucha as disclosed herein orally.
  • the third group is treated with kanna extract containing lipid-based particle composition in kombucha as disclosed herein orally.
  • the fourth group is treated with mushroom extracts containing lipid-based particle composition in kombucha as disclosed herein orally.
  • Groups fifth through eight are treated with kratom, kava, kanna, and mushroom biomass orally in kombucha, respectively.
  • the ninth group of patients is treated with a placebo topically. Groups one through four of patients experiences recovery from pain faster than the groups five through eight and to a higher degree as measured by a self-evaluation. The results show statistically significant improvements in groups one through four relative to either groups five through eight or the ninth group.
  • the patients in groups five through eight show improvement over the placebo, but not to the degree achieved reported by groups one through four.
  • the patients in groups five through eight have statistically higher reports of side effects associated with treatment than either groups one through four or the ninth group.
  • the first group is treated with a kratom containing lipid-based particle composition in kombucha as disclosed herein orally.
  • the second group is treated with kava extract containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • the third group is treated with kanna extract containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • the fourth group is treated with mushroom extracts containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • Groups fifth through eight are treated with kratom, kava, kanna, and mushroom biomass orally in kombucha, respectively.
  • the ninth group of patients are treated with a placebo orally.
  • the patients in groups one through four report less cramping and less severity of cramping. After oral ingestion, the patients in the groups one through four report having an improved moods.
  • the results show statistically significant improvements in groups one through four relative to groups five through eight or the ninth group.
  • the patients in groups five through eight show improvement over the placebo, but not to the degree achieved reported by groups one through four.
  • the patients in groups five through eight have statistically higher reports of side effects associated with treatment than either groups one through four or the ninth group.
  • the first group is treated with a kava and mushroom extract containing lipid-based particle composition in kombucha as disclosed herein orally.
  • the second group of patients is treated orally with a kava and mushroom suspension composition in kombucha orally.
  • the third group of patients is treated with a placebo orally.
  • the first of patients experience recovery from each of the symptoms of anxiety faster than the second group and to a higher degree as measured by a self-evaluation.
  • the patients in the first and second groups report less feelings of nervousness, less feelings of restlessness, less feelings of impending danger, panic or doom, less trouble concentrating, less trouble sleeping.
  • Patients in the first group report less symptoms than compared to the second group. After oral ingestion, the patients in the first and have lower heart rates and less trembling than those in the third group.
  • the first group of patients experience lower systemic levels of the hormone cortisol compared to measurements prior to oral treatment and compared to patients in groups two and three. The results show statistically significant improvements in the first group relative to either the second group or the third group.
  • the patients in the second group show improvement over the placebo, but not to the degree achieved reported by the first group.
  • the patients in the third group have statistically higher reports of side effects associated with treatment than either the first and second group.
  • [00418] Four groups of female and male patients of age between 25 and 40 are admitted to treatment after having had been diagnosed with pain due to exercise related injuries.
  • the first group is treated with a kratom extract, alpha-fenchome, and guaiacel containing lipid-based particle composition in kombucha as disclosed herein orally.
  • the second group is treated with a alpha-fenchome, guaiacel, para-cymene, and/or beta-camophyliene containing lipid- based particle composition in kombucha as disclosed herein orally.
  • the third group of patients is treated orally with a competitor liposomal kratom based composition in kombucha made with kratom leaf powder.
  • the fourth group of patients is treated with a placebo in kombucha.
  • the first and second groups of patients experience recovery from pain faster than the third group and to a higher degree as measured by a self-evaluation.
  • the results show statistically significant improvements in the first and second groups relative to either the third group or the fourth group.
  • the patients in the third group show improvement over the placebo, but not to the degree achieved reported by the first or second groups.
  • the patients in the third and fourth groups have statistically higher reports of side effects associated with treatment than either the first and second groups.
  • the first group is treated with an alpha-fenchome, alpha-terpineol, and bisabolol containing lipid-based particle composition in kombucha as disclosed herein orally.
  • the second group is treated with a kava, alpha-fenchome, alpha-terpineol, and bisabolol containing lipid-based particle composition in kombucha as disclosed herein orally.
  • the third group of patients is treated orally with a kava biomass in a composition in kombucha.
  • the fourth group of patients is treated with a placebo orally. Joint inflammation is measured after two weeks of twice a day administration of the formulations.
  • the first and second groups of patients experience less inflammation than the third group at a statistically significant level.
  • the second group also experiences les inflammation than the first group.
  • the patients in the third group show statistically significant improvement over the placebo, but not to the degree achieved reported by the first or second groups.
  • the patients in the third group have statistically higher reports of side effects associated with treatment than either the first, second, or fourth groups.
  • Example 52 Method of Increasing Sexual Function and Libido Adult Men
  • the first group of patients had statistically significantly improved levels of sexual function and libido compared to their respective pre-study measurements, compared to groups two and three.
  • the patients in the second and third group had no significant increase in sexual function and libido compared to their respective baseline measurements.
  • the first group is treated with a kratom extract containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • the second group is treated with kava extract containing lipid- based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • the third group is treated with kanna extract containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • the fourth group is treated with mushroom extracts containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • Groups fifth through eight are treated with kratom, kava, kanna, and mushroom biomass in kombucha, respectively.
  • the ninth group of patients is treated with a placebo in kombucha orally on a daily schedule.
  • the results show statistically significant improvements in groups one through four relative to either groups five through eight or the ninth group.
  • the patients in groups five through eight have statistically higher reports of side effects associated with treatment than either groups one through four or the ninth group.
  • the patients in the groups one through four have electrical activity in the brain that is more similar to a non-epileptic patient than either groups five through eight or the ninth group. The electrical activity is measured using an electroencephalogram.
  • a patient experiencing a seizure can be treated with either a kratom, kanna, kava, or mushroom extract containing lipid-based particle composition as disclosed herein orally to reduce the severity of seizure and/or shorten the duration, or combinations of extracts in a lipid particle composition (unlike comparator products containing each as a biomass).
  • Ninth groups of female and male patients of age between 25 and 40 are admitted to treatment after having had been diagnosed with diabetes.
  • the first group is treated with a kratom extract containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • the second group is treated with kava extract containing lipid- based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • the third group is treated with kanna extract containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • the fourth group is treated with mushroom extracts containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • Groups fifth through eight are treated with kratom, kava, kanna, and mushroom biomass in kombucha, respectively.
  • the ninth group of patients is treated with a placebo in kombucha orally on a daily schedule.
  • the results show statistically significant improvements in groups one through four relative to either groups five through eight or the ninth group.
  • the patients in groups five through eight have statistically higher reports of side effects associated with treatment than either groups one through four or the ninth group.
  • groups one through four also experiences lowering arterial inflammation due to the antioxidant properties of the extracts, reducing neuropathic pain, a complication of diabetes, increased opening of blood vessels (which may reduce blood pressure over time and improve circulation), relief from muscle cramps, and relief from gastrointestinal pain and cramping.
  • Ninth groups of female and male patients of age between 25 and 55 are admitted to treatment after having had been diagnosed with a form of cancer (breast, colon, prostate, glioma, etc.).
  • the first group is treated with a kratom extract containing lipid-based particle composition in kombucha as disclosed herein intravenously on a daily schedule.
  • the second group is treated with kava extract containing lipid-based particle composition in kombucha as disclosed herein intravenously on a daily schedule.
  • the third group is treated with kanna extract containing lipid-based particle composition in kombucha as disclosed herein intravenously on a daily schedule.
  • the fourth group is treated with mushroom extracts containing lipid-based particle composition in kombucha as disclosed herein on a daily schedule.
  • Groups fifth through eight are treated with kratom, kava, kanna, and mushroom extracts in kombucha, respectively.
  • the ninth group of patients is treated with a placebo in kombucha on a daily schedule.
  • the results show statistically significant improvements in the groups one through four relative to either groups five through eight or the ninth group.
  • the patients in groups five through eight have statistically higher reports of side effects associated with treatment than either groups one through four or the ninth group.
  • the first group is treated with a kratom extract containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • the second group is treated with kava extract containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • the third group is treated with kanna extract containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • the fourth group is treated with mushroom extracts containing lipid-based particle composition in kombucha as disclosed herein orally on a daily schedule.
  • Groups fifth through eight are treated with kratom, kava, kanna, and mushroom in kombucha orally with extracts, respectively.
  • the ninth group of patients is treated with a placebo in kombucha orally on a daily schedule.
  • the results show statistically significant improvements in the groups one through four relative to either groups five through eight or the ninth group.
  • the patients in the groups one through four report less feelings of nervousness, less feelings of restlessness, less feelings of impending danger, panic or doom, less trouble concentrating, less trouble sleeping due to opioid withdraw.
  • After oral ingestion the patients in groups one through four have lower heart rates and less trembling than those in groups five through eight.
  • the results show statistically significant improvements in the groups one through four relative to either groups five through eight or the ninth group.
  • Example 57 Method of Treating a Condition
  • At least three groups of female and male patients are admitted to treatment after having had been diagnosed with a condition, or are at risk of a condition, or are in need of treatment for a condition.
  • Non-limiting conditions and therapeutic ingredients for such conditions may include dihydromyrciten for liver protection, dihydromyrciten for hangover prevention, vitamins for vitamin deficiency, CoQlO and/or omega 3 fatty acids for alcohol related heart disease, and/or phosphatidylserine, huperzine A, and/or Bacopa monnieri extract for alcohol related neurological conditions.
  • a first group is treated orally with a therapeutic containing lipid-based particle composition in a beverage as disclosed herein and on a schedule, such as a daily schedule.
  • a second group is treated with the therapeutic ingredient not contained in a lipid-based particle in a similar beverage orally and on the same schedule.
  • a third group is treated with a placebo in a similar beverage orally and on the same schedule.
  • Group one of patients experience an improvement in the condition or symptoms of the condition. The results show statistically significant improvements in group one relative to either groups two or three.
  • Example 58 Method of Testing Encapsulated Ingredient Stability in Alcoholic Drink
  • Encapsulated ingredients can be introduced to an alcoholic drinks at one or more concentration, such as at 0.263 mg/gm on a weight per weight basis.
  • the finished product containing the encapsulated ingredient can be mixed until the product is homogenous.
  • the finished product can be divided into individual vials, capped, and placed at the recommended storage condition, such as at 2 - 8°C, for a period of time, such as 6 months.
  • the product can be removed from storage and assessed for visual appearance, microbiology, concentration of ingredient remaining (percent remaining), formation of substances from degradation of the ingredient, such as delta 9 THC for CBD, and size of the encapsulated ingredient, such as nanoparticle size.
  • Microbiology can be tested to determine the amount of living microbes in the finish product by spectroscopy, plating (e.g. agar plates), live/dead staining, etc.
  • concentration of ingredients remaining and/or formation of substances from degradation of the ingredient can be determined by High Performance Liquid Chromatography (HPLC), Gas Chromatography (GC), Mass Spectrometry (MS), etc.
  • the size of the encapsulated ingredient can be determined by dynamic light scattering (DLS), Scanning Electron Microscopy (SEM), cryogenic SEM (cryo-SEM), etc.

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Abstract

Certains modes de réalisation concernent une composition à base particulaire employée dans une boisson et son utilisation dans des procédés pour l'administration d'agents thérapeutiques à des sujets. Dans plusieurs modes de réalisation, les compositions sont stables pendant des intervalles de temps prolongés et présentent une biodisponibilité améliorée.
PCT/IB2022/060018 2021-10-18 2022-10-18 Compositions pour complémenter des produits de kombucha avec des agents thérapeutiques et leurs procédés de fabrication et d'utilisation WO2023067509A1 (fr)

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