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WO2025147521A2 - Formulations de particules de microémulsion et boissons enrichies en particules de microémulsion - Google Patents

Formulations de particules de microémulsion et boissons enrichies en particules de microémulsion Download PDF

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Publication number
WO2025147521A2
WO2025147521A2 PCT/US2025/010098 US2025010098W WO2025147521A2 WO 2025147521 A2 WO2025147521 A2 WO 2025147521A2 US 2025010098 W US2025010098 W US 2025010098W WO 2025147521 A2 WO2025147521 A2 WO 2025147521A2
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WO
WIPO (PCT)
Prior art keywords
component
microemulsion
beverage
payload
weeks
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
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PCT/US2025/010098
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English (en)
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WO2025147521A3 (fr
Inventor
Aaron C. Anselmo
Jinning Liu
Gwangseong Kim
Stephanie TOMASIC
Olivia BROWN
Alexandria HWANG
Anant S. BALIJEPALLI
Andrea Stamp
Ana Jaklenec
Catherine B. Reynolds
Robert S. Langer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Vitakey Inc
Original Assignee
Vitakey Inc
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Publication date
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Publication of WO2025147521A2 publication Critical patent/WO2025147521A2/fr
Publication of WO2025147521A3 publication Critical patent/WO2025147521A3/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
    • A23L2/52—Adding ingredients
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/80—Emulsions
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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 OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L35/00—Foods or foodstuffs not provided for in groups A23L5/00 - A23L33/00; Preparation or treatment thereof
    • A23L35/10—Emulsified foodstuffs

Definitions

  • the present disclosure provides a variety of technologies relating to incorporating payload components into beverages.
  • the present disclosure specifically provides technologies for incorporating payload components into microemulsion particle formulations, which are combined with aqueous solutions (i.e., base beverages) to provide ingestible (specifically, drinkable) fortified beverages with one or more beneficial or otherwise desirable attributes.
  • aqueous solutions i.e., base beverages
  • ingestible specifically, drinkable
  • provided technologies identify the source of one or more problems with conventional approaches to incorporating certain payloads into beverages, and solve such problems.
  • the present disclosure documents success of provided technologies with a variety of different payloads (specifically including each of lutein, Vitamin D2, Vitamin B12, and caffeine) in microemulsion particle formulations prepared from various components (e g., fatty component, surfactant component and, optionally, one or more antioxidant and/or stabilizing components).
  • various components e g., fatty component, surfactant component and, optionally, one or more antioxidant and/or stabilizing components.
  • microemulsion technologies may be particularly useful for introducing and/or maintaining payload(s) in beverage(s).
  • the present disclosure demonstrates that microemulsion technologies as described herein can achieve long term stable maintenance of payload(s) of interest, in some embodiments in diverse beverages (e.g., in beverages of different pHs and/or including different components) and/or may achieve desirable release characteristics over time.
  • the present disclosure further documents that such release characteristics are stable even after storage of a provided microemulsion particle formulation (containing a payload of interest) in a beverage (including, for example, a sports drink or a soda, e.g., a carbonated soda).
  • Some embodiments of provided technologies may utilize payload in a solid form.
  • some embodiments of provided technologies encompass a recognition that in certain contexts microemulsion particle formulations are desirably prepared and/or maintained in liquid form, or at least without component(s) (e.g., payload component(s) in a solid form).
  • component(s) e.g., payload component(s) in a solid form.
  • the present disclosure appreciates that other reports describe technologies where, for example, explicit drying and/or isolation steps are performed in order to provide a payload component in a solid form, which may then be incorporated into an emulsion (see, for example, WO2022266442, which describes preparation of caffeine:tannic acid complexes by drying or otherwise isolating solid precipitates and, in some embodiments, including them in an emulsion composition).
  • the present disclosure by contrast, demonstrates desirable stability of provided microemulsion particle formulations, including of desirable release characteristics.
  • the present disclosure documents stability (including absence of payload release) of provided microemulsion particle formulations, even after combination with, and storage in, base beverages.
  • the present disclosure further demonstrates extended release of payload over a period of hours after simulated ingestion of a fortified beverage, and maintenance of such release characteristics after storage of such fortified beverage (i .e., storage of a provided microemulsion particle formulation in a base beverage).
  • avoiding solid-phase payload components may permit preparation of more tunable microemulsion particle formulations, for example facilitating bespoke design of such formulations for inclusion in particular beverage(s) of interest.
  • the present disclosure also demonstrates that certain provided microemulsion particle formulations are characterized by stable attributes when combined with various different base beverages (e.g., with different pHs and/or other different components (e.g., flavors, fragrances, vitamins, stimulants (e.g., caffeine) and/or levels and/or combinations thereof).
  • base beverages e.g., with different pHs and/or other different components (e.g., flavors, fragrances, vitamins, stimulants (e.g., caffeine) and/or levels and/or combinations thereof).
  • provided formulations have beneficial particle size characteristics (e.g., average size and/or particles size distribution characteristics) so that among other things, combination of provided microemulsion particle formulations with base beverages does not negatively impact aspects of the beverages, such as turbidity or other visual characteristics.
  • the present disclosure documents that such particle size characteristics are maintained over time, including after combination with, and storage in, such base beverage.
  • fortified beverage composition has been stored for a period of time that is at least 8 weeks.
  • the present disclosure is directed to methods for fortifying a beverage, e g., methods comprising: i) providing a microemulsion particle formulation as described herein; and ii) combining the microemulsion particle formulation with the beverage to produce a fortified beverage; as described herein, in many embodiments, a microemulsion particle formulation utilized in such combination comprises one or more microemulsion particles and at least 79 wt% water, and the one or more microemulsion particles comprises: 0.01 wt% to 0.13 wt% of a payload component; 0.1 wt% to 2 wt% of a fatty component; 12 wt% to 20 wt% of a surfactant component; 0.1 wt% to 2 wt% of an antioxidant component; and 0.1 wt% to 4 wt% of a stabilizing component.
  • providing a microemulsion particle formulation comprises: i) preparing an aqueous phase; ii) preparing an oil phase; and iii) combining the aqueous and the oil phases so that the microemulsion particle formulation, comprising a plurality of microemulsion particles is produced.
  • preparing an aqueous phase comprises mixing water and an antioxidant component; and ii) preparing an oil phase comprises mixing a payload component, an oil component, a surfactant component, and a stabilizing component.
  • payload components comprise lutein, vitamin D, zeaxanthin, vitamin B 12, or a combination thereof.
  • preparing an aqueous phase comprises mixing water, a payload component, and an antioxidant component; and ii) preparing an oil phase comprises mixing an oil component, a surfactant component, and a stabilizing component.
  • the payload comprises caffeine.
  • the formulation comprises the payload component and tannic acid in a combined weight percent in a range from 8 wt% to 9 wt%.
  • FIG. 3A - FIG. 3B are plots of particle diameter size (FIG. 3A) and turbidity (FIG. 3B) of microemulsion particle formulations and non-microemulsion particle formulations according to illustrative embodiments of the present disclosure;
  • FIG. 4A - FIG. 4B are plots of particle diameter size (FIG. 4A) and turbidity (FIG. 4B) of microemulsion particle formulations and non-microemulsion particle formulations (“Omniactive”) according to illustrative embodiments of the present disclosure;
  • FIG. 4C - FIG. 4D are photographs of samples of water including microemulsion particle formulations at day 0 (FIG. 4C) and day 30 (FIG. 4D) according to illustrative embodiments of the present disclosure;
  • FIG. 5A - FIG. 5B are plots of particle diameter size (FIG. 5A) and turbidity (FIG. 5B) of microemulsion particle formulations and non-microemulsion particle formulations (“Omniactive”) according to illustrative embodiments of the present disclosure;
  • FIG. 5C - FIG. 5D are photographs of samples of a Red BullTM energy drink including microemulsion particle formulations at day 0 (FIG. 5C) and day 30 (FIG. 5D) according to illustrative embodiments of the present disclosure;
  • FIG. 6A - FIG. 6B are plots of particle diameter size (FIG. 6A) and turbidity (FIG. 6B) of microemulsion particle formulations and non-microemulsion particle formulations (“Omniactive”) according to illustrative embodiments of the present disclosure;
  • FIG. 6C - FIG. 6D are photographs of samples of a MonsterTM energy drink including microemulsion particle formulations at day 0 (FIG. 6C) and day 30 (FIG. 6D) according to illustrative embodiments of the present disclosure;
  • FIG. 7A - FIG. 7B are plots of particle diameter size (FIG. 7A) and turbidity (FIG. 7B) of microemulsion particle formulations and non-microemulsion particle formulations (“Omniactive”) according to illustrative embodiments of the present disclosure
  • FIG. 7C - FIG. 7D are photographs of samples of a RockstarTM energy drink including microemulsion particle formulations at day 0 (FIG. 7C) and day 30 (FIG. 7D) according to illustrative embodiments of the present disclosure;
  • FIG. 8A - FIG. 8B are plots of particle diameter size (FIG. 8A) and turbidity (FIG. 8B) of microemulsion particle formulations and non-microemulsion particle formulations (“Omni active”) v. their concentration in a RockstarTM energy drink, according to illustrative embodiments of the present disclosure;
  • FIG. 8C - FIG. 8D are photographs of samples of a RockstarTM energy drink including non-microemulsion particle formulations (FIG. 8C) and microemulsion particle formulations (FIG. 8D) at varying concentrations according to illustrative embodiments of the present disclosure;
  • FIG. 9A is a plot presenting stability of lutein as a payload component in microemulsion particle formulations included in a MonsterTM energy drink according to illustrative embodiments of the present disclosure
  • FIG. 9B shows photographs of samples of a plain MonsterTM energy drink (left panel), a MonsterTM energy drink including a microemulsion particle formulation (middle panel), and a MonsterTM energy drink including a non-microemulsion particle formulation (right panel) according to illustrative embodiments of the present disclosure;
  • FIG. 9C is a plot presenting stability of lutein as a payload component in both microemulsion particle formulations and non-microemulsion particle formulations (“Omniactive”) included in a MonsterTM energy drink according to illustrative embodiments of the present disclosure;
  • FIG. 9D shows photographs of samples of a plain MonsterTM energy drink (left panel), a MonsterTM energy drink including a non-microemulsion particle formulation (centerleft panel), a MonsterTM energy drink including a microemulsion particle formulation (centerright panel and right panel) according to illustrative embodiments of the present disclosure
  • FIG. 11C is a plot presenting stability of lutein as a payload component in microemulsion particle formulations according to illustrative embodiments of the present disclosure.
  • FIG. 16A - FIG. 16B are plots presenting release performance characteristics of microemulsion particle formulations comprising caffeine as a payload component when formulations are stored for 6 weeks with exposure to light in a MonsterTM energy drink according to illustrative embodiments of the present disclosure;
  • the term “about” or “approximately” means within 10%, preferably within 10%, and more preferably within 5% of a given value or range.
  • Ambient refers to a typical indoor (e.g., climate-controlled) temperature, usually within a range of about 18° C to about 32° C, and/or typical indoor (e g., climate-controlled) humidity, usually within a range of about 30% to 50%.
  • ambient temperature is within a range of about 20° C to about 30° C.
  • ambient temperature is 25 ⁇ 5° C.
  • ambient temperature is approximately 21° C.
  • ambient temperature is 18° C.
  • ambient temperature is 19° C.
  • ambient temperature is 20° C.
  • ambient temperature is 21° C.
  • ambient temperature is 22° C.
  • ambient temperature is 23° C. In some embodiments, ambient temperature is 24° C. In some embodiments, ambient temperature is 25° C. Tn some embodiments, ambient temperature is 26° C. In some embodiments, ambient temperature is 27° C. In some embodiments, ambient temperature is 28° C. In some embodiments, ambient temperature is 29° C. In some embodiments, ambient temperature is 30° C. In some embodiments, ambient may be used to describe outdoor conditions, and may include temperatures ranging from about 15° C to about 40° C, or from about 25° C to about 40° C. In some embodiments, ambient humidity is within a range of about 35% to about 45%. In some embodiments, ambient temperature is 35%. In some embodiments, ambient temperature is 36%.
  • ambient temperature is 37%. In some embodiments, ambient temperature is 38%. In some embodiments, ambient temperature is 39%. In some embodiments, ambient temperature is 40%. In some embodiments, ambient temperature is 41%. In some embodiments, ambient temperature is 42%. In some embodiments, ambient temperature is 43%. In some embodiments, ambient temperature is 44%. In some embodiments, ambient temperature is 45%.
  • Beverage As used herein, the term “beverage” is used to refer to a potable liquid (e.g., that can be ingested, swallowed, drunk, or consumed by a person or animal without material risk to the person or animal).
  • a beverage can be or include an energy drink, water, nutrient-fortified water, carbonated drink, coffee, tea, juice, milk, milk alternative, or baby formula.
  • a “beverage” may be or comprise a formulation of the present disclosure in liquid form.
  • Biocompatible As used herein, the term “biocompatible” is used to describe a characteristic of not causing significant detectable harm to living tissue when placed in contact therewith e.g., in vivo. In certain embodiments, materials are “biocompatible” if they are not significantly toxic to cells, e.g., when contacted therewith in a relevant amount and/or under relevant conditions such as over a relevant period of time. In certain embodiments, materials are “biocompatible” if their addition to cells in vitro results in less than or equal to 20% cell death, and/or their administration in vivo does not induce significant inflammation or other adverse effects.
  • Comparable refers to two or more agents, entities, situations, sets of conditions, etc., that may not be identical to one another but that are sufficiently similar to permit comparison therebetween so that one skilled in the art will appreciate that conclusions may reasonably be drawn based on differences or similarities observed. Tn some embodiments, comparable sets of conditions, circumstances, individuals, or populations are characterized by a plurality of substantially identical features and one or a small number of varied features. Those of ordinary skill in the art will understand, in context, what degree of identity is required in any given circumstance for two or more such agents, entities, situations, sets of conditions, etc. to be considered comparable.
  • Degradation refers to a change in chemical structure and often involves breakage of at least one chemical bond. To say that a chemical compound is degraded typically means that the chemical structure of the chemical compound has changed (e.g., a chemical bond is broken). Common mechanisms of degradation include, for example, oxidation, hydrolysis, isomerization, fragmentation, or a combination thereof.
  • Diameter As used herein, the term “diameter” is used to refer to the longest distance from one end of a particle to another end of the particle. Those skilled in the art will appreciate that a variety of techniques are available for use in characterizing particle diameters (i.e., particle sizes). In some instances, for example, size of particles (e.g., diameter of particles) can be measured by a Coulter Counter. In some instances, for example, size of particles (e.g., diameter of particles) can be measured by a Malvern Mastersizer.
  • a population of particles is characterized by an average size (e.g., D[3,2], D[4,3], etc.) and/or by particular characteristics of size distribution (e.g., absence of particles above or below particular sizes [e.g., DvlO, Dv20, Dv30, Dv40, Dv50, Dv60, Dv70, Dv80, Dv90, Dv99, etc ], a unimodal, bimodal, or multimodal distribution, etc.).
  • an average size e.g., D[3,2], D[4,3], etc.
  • particular characteristics of size distribution e.g., absence of particles above or below particular sizes [e.g., DvlO, Dv20, Dv30, Dv40, Dv50, Dv60, Dv70, Dv80, Dv90, Dv99, etc ], a unimodal, bimodal, or multimodal distribution, etc.
  • Dispersity is used to refer to the breadth of particle size distribution relative to the average particle size
  • HLB is used to refer to the hydrophilic lipophilic balance that is an inherent property of, for example, a nonionic surfactant.
  • the HLB value of a given non-ionic surfactant is obtained from a commonly accessible tabular source.
  • non-ionic surfactants characterized as having a low HLB value e.g., ⁇ 8
  • nonionic surfactants characterized as having a high HLB value e.g., >15
  • non-ionic surfactants characterized as having an intermediate HLB value e.g., >8 and ⁇ 15 are compatible emulsifiers with both lipid and aqueous systems.
  • homogenous As used herein, the term “homogenous” means of substantially uniform structure and/or composition throughout.
  • Hydrophobic As used herein, the term “hydrophobic” is used to refer to the propensity of a material to reject association, chemically and/or physically, with water.
  • a material characterized as being hydrophobic is biologically derived and/or synthetically derived.
  • a material characterized as being hydrophobic is a lipid, protein, and/or carbohydrate.
  • a material characterized as being hydrophobic is a polymer and/or small molecule.
  • composites, mixtures, blends, or super-structures of several materials are collectively referred to as hydrophobic based on their observed propensity to reject association, chemically and/or physically, with water.
  • a particular sample or preparation may be described as layered, independent of its mode of preparation, so long as at a particular point in time and/or using a particular mode of assessment, distinct materials can be identified in a layered structure.
  • a “layered” particle may include one or more layers that wholly encapsulate a material below.
  • a “layered” particle may include one or more layers that does not wholly encapsulate a material below.
  • at least one layer of a layered preparation is or comprises a polymer, e.g., a hydrophobic polymer or hydrophilic polymer.
  • each layer of a layered preparation is or comprises a polymer, e g., a pH responsive polymer or a temperature- responsive polymer.
  • lipid As used herein, the term “lipid” is used to refer to a class of chemical structures characterized as hydrophobic materials. In some instances, a lipid material is derived from a biological source. In other instances, a lipid material is derived from a synthetic source. In some instances, a lipid comprises one or more aliphatic alcohols and/or acids linked by glycerol and/or glycol moieties. In other instances, a lipid comprises aliphatic chains, linear conjugated, aromatic, and/or cyclic aliphatic moieties. In some embodiments, a lipid refers to a pure chemical entity. In other embodiments, a lipid refers to a mixture of several pure chemical entities.
  • the pressure is lowered to ⁇ 200 torr, ⁇ 150 torr, ⁇ 100 torr, ⁇ 50 torr, ⁇ 10 torr, ⁇ 5 torr, and/or ⁇ 1 torr.
  • Particle As used herein, the term “particle” is used to refer to a discrete physical entity, typically having a size (e.g., a longest cross-section, such as a diameter) within a range.
  • a particle can have a size of 5 nm to 150 nm, about 10 nm to 150 nm, about 15 nm to 150 nm, about 20 nm to 150 nm, about 25 nm to 150 nm, about 30 nm to 150 nm, about 35 nm to 150 nm, about 40 nm to 150 nm, about 45 nm to 150 nm, about 50 nm to 150 nm, about 55 nm to 150 nm, about 60 nm to 150 nm, about 65 nm to 150 nm, about 70 nm to 150 nm, about 75 nm to 150 nm, about 80 nm to 150 nm, about 85 nm to 150 n
  • nm to 100 nm about 10 nm to 100 nm, about 15 nm to 100 nm, about 20 nm to 100 nm, about 25 nm to 100 nm, about 30 nm to 100 nm, about 35 nm to 100 nm, about 40 nm to 100 nm, about 45 nm to 100 nm, about 50 nm to 100 nm, about 55 nm to 100 nm, about 60 nm to 100 nm, about 65 nm to 100 nm, about 70 nm to 100 nm, about 75 nm to 100 nm, about 80 nm to 100 nm, about 85 nm to 100 nm, about 90 nm to 100 nm, about 95 nm to 100 nm, about 5 nm to 100 nm, about 10 nm to 100 nm, about 15 nm to 100 nm, about 20 nm to 100 nm, about 25 n
  • 75 nm about 15 nm to 75 nm, about 20 nm to 75 nm, about 25 nm to 75 nm, about 30 nm to 75 nm, about 35 nm to 75 nm, about 40 nm to 75 nm, about 45 nm to 75 nm, about 50 nm to 75 nm, about 55 nm to 75 nm, about 60 nm to 75 nm, about 65 nm to 75 nm, about 5 nm to 50 nm, about 10 nm to 50 nm, about 15 nm to 50 nm, about 20 nm to 50 nm, about 25 nm to 50 nm, about 30 nm to 50 nm, about 35 nm to 50 nm, about 40 nm to 50 nm, about 45 nm to 50 nm, about 5 nm to 25 nm, about 10 nm to 25 nm, about 15 nm to 25
  • pH Responsive is used to refer to certain polymer component(s) as described herein, and in particular means that the relevant polymer component is characterized in that one or more aspects of its structure or arrangement is altered when exposed to a change in pH condition (e.g., to a particular pH and/or to a pH change of particular magnitude).
  • a polymer component is considered to be “pH-responsive” if, when the relevant polymer component is associated with a payload component in a particle preparation as described herein, the particle preparation releases the payload component under specific pH condition(s).
  • >90% of payload component is released from a particle preparation that includes a pH-responsive polymer component within 15 minutes when the particle preparation is exposed to a particular defined pH condition (e.g., within a range of defined pH values and/or at a specific pH value); in some embodiments, such release results when such contacting occurs at temperatures between 33-40 °C, and in aqueous-based buffers of ionic strength ranging from 0.001-0.151 M (e.g., water, simulated gastric fluid, gastric fluid, simulated intestinal fluid, intestinal fluid) with osmolality between 1-615 mOsm/kg.
  • a pH-responsive polymer component is one that degrades when exposed to a particular pH or pH change.
  • Reference As used herein describes a standard or control relative to which a comparison is made. For example, in some embodiments, an agent, animal, individual, population, sample, sequence or value of interest is compared with a reference or control agent, animal, individual, population, sample, sequence or value. In some embodiments, a reference or control is tested and/or determined substantially simultaneously with the testing or determination of interest. In some embodiments, a reference or control is a historical reference or control, optionally embodied in a tangible medium. Typically, as would be understood by those skilled in the art, a reference or control is determined or characterized under comparable conditions or circumstances to those under assessment. Those skilled in the art will appreciate when sufficient similarities are present to justify reliance on and/or comparison to a particular possible reference or control.
  • a polymer component is considered to be “temperature-responsive” if, when the relevant polymer component is associated with a payload component in a particle preparation as described herein, amorphous regions of the polymer component experience a transition from a rigid state (e.g., glassy state) to a more fluid-like flexible state (e.g., more conducive to flow), at a temperature close to the point of transition from the solid state to rubbery state (e.g., glass transition).
  • a rigid state e.g., glassy state
  • a more fluid-like flexible state e.g., more conducive to flow
  • Water activity As used herein, “water activity” of a material is an indication (e.g., a measurement) of how much free (i.e., available to bind or react) water is present in the material and is typically determined as the ratio of the vapor pressure of water in a material (p) to the vapor pressure of pure water (po) at the same temperature. For example, a water activity of 0.80 means the vapor pressure is 80 percent of that of pure water. Water activity typically increases with temperature.
  • Preventive Electrolytic Hygrometers REH
  • Capacitance Hygrometers Capacitance Hygrometers
  • Dew Point Hygrometers sometimes called chilled mirror.
  • a first layer on a second layer in some embodiments means a first layer directly on and in contact with a second layer. In other embodiments, a first layer on a second layer can include another layer there between.
  • the present disclosure provides formulations including one or more microemulsion particles and at least 80% w/v water, wherein the one or more microemulsion particles incorporate a payload component, a fatty acid component, a surfactant component, an antioxidant component, and a stabilizing component.
  • a microemulsion particle formulation of the present disclosure does not form aggregates, flocculates, bezoars, or sediments when combined with one or more aqueous solutions (for example, when combined with one or more beverages such as, for example, with one or more of coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula).
  • beverages such as, for example, with one or more of coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula.
  • a microemulsion particle formulation of the present disclosure does not form aggregates, flocculates, bezoars, or sediments when added to one or more aqueous solutions (for example, with a beverage such as, for example, one or more of coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, and/or baby formula) following storage in such aqueous solution for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.
  • a beverage
  • release of a payload component from a microemulsion particle formulation described herein into a solution is delayed as compared to an appropriate reference (e.g., to free payload component and/or to non-emulsified payload component).
  • a microemulsion particle formulation of the present disclosure that includes a payload component is characterized in that such payload component displays a reduced diffusion coefficient in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) after such a microemulsion particle formulation has been combined with such aqueous solution and the combination has been stored for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months
  • a microemulsion particle formulation of the present disclosure that includes a payload component is characterized in that the payload component maintains a diffusion coefficient that is reduced by at least about 10%, at least about 20%, at least about 50%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 99.9%, at least about 99.99%, at least about 99.999%, or at least about 99.9999% as compared to a diffusion coefficient of an appropriate reference (e.g., a free payload component or a non-emulsified payload component) following storage in an aqueous solution (for example, in a beverage such as, for example, in coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days
  • a microemulsion particle formulation of the present disclosure that includes a payload component is characterized in that, when the formulation is combined with an aqueous solution (e.g., with a beverage such as, for example, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) a concentration equilibrium of the payload component is maintained between particles of the formulation and the aqueous solution with which it is combined (which aqueous solution may be referred to as “exterior” relative to the particles); in some such embodiments, such a concentration equilibrium is maintained for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8
  • an aqueous solution
  • a payload component concentration equilibrium is calculated as a ratio of a payload component concentration within particles of the formulation and a payload component concentration in an exterior aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula).
  • a beverage e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula.
  • a payload component concentration equilibrium is a ratio of about 500:1, about 450: 1, about 400: 1, about 350: 1, about 300: 1, about 250:1, about 200: 1, about 150: 1, about 100: 1, about 75: 1, about 50: 1, about 25: 1, about 10: 1, about 9: 1, about 8: 1, about 7:1, about 6: 1, about 5:1, about 4: 1, about 3:1, about 2: 1, or about 1.5: 1 following storage of a microemulsion of the present disclosure in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks,
  • an aqueous solution
  • a concentration equilibrium is modulated in response to the presence of one or more environmental factors.
  • a concentration equilibrium is modulated such that a ratio of a payload component concentration within particles of a microemulsion particle formulation and a payload component concentration in an exterior aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented nonalcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) increases in the presence of one or more environmental factors as compared to a ratio in the absence of the one or more environmental factors.
  • a beverage e.g., coconut water, sparkling water, fermented nonalcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula
  • a concentration equilibrium is modulated such that a ratio of a payload component concentration within particles of a microemulsion particle formulation and a payload component concentration in an exterior aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) decreases in the presence of one or more environmental factors as compared to a ratio in the absence of the one or more environmental factors.
  • a beverage e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula
  • an environmental factor includes, but is not limited to, an increase or decrease in temperature, an increase or decrease in concentration of the payload component in the aqueous solution, enzymatic digestion, bile salts, pH, microbes, tonicity, shear, pressure, activation energy, sound, or magnetic field.
  • a microemulsion particle formulation of the present disclosure is characterized by delayed release of a payload component into one or more gastrointestinal compartments of a subject that has ingested the microemulsion particle formulation as compared to release observed upon ingestion of an appropriate reference (e.g., of free payload component and/or of non-emulsified payload component).
  • release of a payload component from a microemulsion particle formulation of the present disclosure is delayed until the microemulsion particle formulation reaches the small intestine of a subject that has ingested the microemulsion particle formulation.
  • a microemulsion particle formulation of the present disclosure increases bioavailability of a payload component in a subject that has ingested the microemulsion particle formulation as compared to that observed for an appropriate reference payload component formulation (e.g., free payload component and/or non-emulsified payload component).
  • an appropriate reference payload component formulation e.g., free payload component and/or non-emulsified payload component.
  • a microemulsion particle formulation of the present disclosure is characterized in that release of a payload component is responsive to the presence of one or more digestive enzymes in a gastrointestinal compartment of a subject that has ingested the microemulsion particle formulation. In some embodiments, a microemulsion particle formulation of the present disclosure is characterized in that release of a payload component is responsive to the presence of one or more digestive enzymes in an oral cavity of a subject that has ingested the microemulsion particle formulation.
  • a microemulsion particle formulation of the present disclosure is characterized in that release of a payload component is responsive to the presence of one or more digestive enzymes in a gastric cavity of a subject that has ingested the microemulsion particle formulation.
  • a microemulsion particle formulation of the present disclosure is characterized in that release of a payload component is responsive to the presence of one or more digestive enzymes in a small intestine of a subject that has ingested the microemulsion particle formulation.
  • a microemulsion particle formulation of the present disclosure is characterized in that release of a payload component is responsive to the presence of one or more digestive enzymes in a colon of a subject that has ingested the microemulsion particle formulation.
  • release of payload component from a provided microemulsion particle formulation described herein is reduced and/or delayed relative to an appropriate reference (e.g., to free payload component and/or to non-emulsified payload component) unless and/or until the provided microemulsion particle formulation encounters such digestive enzyme(s).
  • release may, in some embodiments, be rapid - including in some embodiments relative to one or more other formulations of the same payload component.
  • a microemulsion particle formulation of the present disclosure includes a payload component that is reversibly modified via chemical conjugation to one or more lipophilic moieties.
  • a payload component is chemically conjugated to a fat.
  • a payload component is chemically conjugated to a fatty acid.
  • a reversibly modified payload component has delayed release from a microemulsion particle (and/or from a microemulsion particle formulation) as compared to a payload component that has not been reversibly modified.
  • a lipophilic moiety is removed from a payload component to which it is reversibly conjugated upon ingestion of a microemulsion particle of the present disclosure by a subject. In some embodiments, a lipophilic moiety is removed from a payload component to which it is reversibly conjugated by a digestive enzyme present in a gastrointestinal compartment of a subject upon ingestion of a microemulsion particle of the present disclosure by the subject.
  • a microemulsion particle formulation of the present disclosure is characterized by an internal pH of about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, or about 14.
  • release of a payload component from a microemulsion particle of the present disclosure is reduced when the microemulsion particle is exposed to a pH of about 1.5 to 3.5, about 1 .75 to 3.5, about 2.0 to 3.5, about 2.25 to 3.5, about 2.5 to 3.5, about 2.75 to 3.5, about 3.0 to 3.5, about 3.25 to 3.5, about 1.5 to 3.25, about 1.75 to 3.25, about 2.0 to 3.25, about 2.25 to 3.25, about 2.5 to 3.25, about 2.75 to 3.25, about 3.0 to 3.25, about 1.5 to 3.0, about 1.75 to 3.0, about 2.0 to 3.0, about 2.25 to 3.0, about 2.5 to 3.0, about 2.75 to 3.0, about 1.5 to 2.75, about 1.75 to 2.75, about 2.0 to 2.75, about 2.25 to 2.75, about 2.5 to 2.75, about 1.5 to 2.5, about 1.75 to 2.5, about 2.0 to 2.5, about 2.25 to 2.5, about 1.5 to 2.25, about 1.75 to 2.75, about 2.0 to 2.75, about 2.25 to 2.75
  • release of a payload component from a microemulsion particle (and/or from a microemulsion particle formulation) of the present disclosure is independent of pH and/or is non-responsive to a change in pH.
  • particles of a microemulsion particle formulation of the present disclosure have a same average diameter at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14.
  • particles of a microemulsion particle formulation of the present disclosure have a same average diameter following storage in an aqueous solution (for example, in a beverage, e g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14, for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least
  • a preparation of microemulsion particles (e.g., a microemulsion particle formulation) of the present disclosure is characterized by a distribution of average diameters (e.g., Dv(10), Dv(20), Dv(30), Dv(40), Dv(50), Dv(60), Dv(70), Dv(80), Dv(90), Dv(99), etc.) that is the same at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14.
  • average diameters e.g., Dv(10), Dv(20), Dv(30), Dv(40), Dv(50), Dv(60), Dv(70), Dv(80), Dv(90), Dv(
  • a microemulsion particle formulation of the present disclosure is characterized by a same distribution of average diameters (e.g., Dv(10), Dv(20), Dv(30), Dv(40), Dv(50), Dv(60), Dv(70), Dv(80), Dv(90), Dv(99), etc.) following storage in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient- fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH
  • a microemulsion particle formulation of the present disclosure is characterized by a payload component concentration that is the same at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14.
  • a microemulsion particle formulation of the present disclosure has a same payload component concentration following storage in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14, for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5
  • a microemulsion particle formulation of the present disclosure releases a payload component at a predictable rate upon ingestion of the microemulsion particle by a subject.
  • a microemulsion particle of the present disclosure releases a payload component upon ingestion of the microemulsion particle formulation (e.g., in a fortified beverage as described herein) by a subject at a rate that prolongs a pharmacologic, nutritive, and/or cognitive benefit of the payload component as compared to that achieved with an appropriate reference (e.g., by free payload and/or by non-emulsified payload component).
  • a microemulsion particle formulation of the present disclosure releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 60%, about 60%, about 60%, about 60%, about 60%, about 60%, about 60%, about
  • a microemulsion particle formulation of the present disclosure that has been stored in an aqueous solution (for example, in a beverage, e g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about
  • a microemulsion particle formulation of the present disclosure stored in an aqueous solution for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about
  • a microemulsion particle formulation of the present disclosure releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 60%, about 60%, about 60%, about 60%, about 60%, about 60%, about 60%, about
  • a microemulsion particle formulation of the present disclosure stored in an aqueous solution for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70%
  • a microemulsion particle formulation of the present disclosure releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 60%, about 60%, about 60%, about 60%, about 60%, about 60%, about 60%, about
  • a microemulsion particle formulation of the present disclosure stored in an aqueous solution (for example, in a beverage, e g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to
  • the present disclosure additionally provides beverages that have been fortified with microemulsion particle formulations as described herein, e.g., including a payload component, a fatty acid component, a surfactant component, an antioxidant component, and a stabilizing component.
  • aqueous phase e g., a base beverage
  • particle phase e.g., that is or comprises particles of a microemulsion particle formulation
  • a particular payload e.g., caffeine
  • a particular payload is present in both the particle phase and the aqueous phase of a provided fortified beverage.
  • a formulated beverage is characterized by one or more features of payload release (e.g., extended release) as described herein.
  • a provided formulated beverage has been stored for a period of time (e.g., as set forth herein); in certain such embodiments, such a stored formulated beverage is characterized by one or more features of payload release that is reasonably comparable to that observed for the fortified beverage prior to such storage.
  • a formulation of the present disclosure is added to a base beverage to produce the fortified beverage.
  • a base beverage is selected from, but not limited to, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula.
  • a base beverage is Monster TM or Red BullTM energy drink.
  • a base beverage is oatmilk or OatlyTM beverage.
  • a fortified beverage of the present disclosure includes about 0.1 w/v% to 5 w/v% of a payload component.
  • a fortified beverage of the present disclosure includes about 0.1 w/v% to 5 w/v%, about 0.25 w/v% to 5 w/v%, about 0.5 w/v% to 5 w/v%, about 0.75 w/v% to 5 w/v%, about 1 w/v% to 5 w/v%, about 1.25 w/v% to 5 w/v%, about 1.5 w/v% to 5 w/v%, about 1.75 w/v% to 5 w/v%, about 2.0 w/v% to 5 w/v%, about 2.25 w/v% to 5 w/v%, about 2.5 w/v% to 5 w/v%, about 2.75 w/v% to 5 w/v%, about 3 w/v/v
  • w/v% about 1 w/v% to 3.5 w/v%, about 1.25 w/v% to 3.5 w/v%, about 1.5 w/v% to 3.5 w/v%, about 1.75 w/v% to 3.5 w/v%, about 2.0 w/v% to 3.5 w/v%, about 2.25 w/v% to 3.5 w/v%, about 2.5 w/v% to 3.5 w/v%, about 2.75 w/v% to 3.5 w/v%, about 3 w/v% to 3.5 w/v%, about 3.25 w/v% to 3.5 w/v%, about 0.1 w/v% to 3 w/v%, about 0.25 w/v% to 3 w/v%, about 0.5 w/v% to 3 w/v%, about 0.75 w/v% to 3 w/v%, about 1 w/v% to 3 w/v%, about 1.25
  • a base beverage comprises a concentration of a payload component that is less than the concentration of the payload component in a microsome particle of the present disclosure, thereby establishing a concentration gradient across the liposomal membrane.
  • a concentration of a payload component in a base beverage is in equilibrium with a concentration of the payload component in a microsome particle of the present disclosure.
  • Lutein Recovery To evaluate the stability that microemulsion particle formulations provide to lutein as a payload component the percent recovery was determined by quantifying the amount of lutein in a sample at a particular time interval. 9.9 mL of a beverage was added to a 12 mL glass vial and 100 pL of a microemulsion formulation was then added to the 12 mL glass vial. The vial was covered with a rubber stopper and aluminum seal, crimped shut, and vortexed to ensure proper mixing. The contents of the vial were measured for lutein recovery in replicates of three at time intervals of 0 days, 7 days, 14 days, 28 days, and 56 days.
  • lutein recovery was calculated as the percentage ratio of the average lutein peak area for each timepoint relative to the average lutein peak area at timepoint 0 days.
  • microemulsion particle formulations comprising lutein were compared to Omni ActiveTM Lutemax 2020 particle formulations (i.e., non-microemulsion particle formulations) for lutein stability performance characteristics (as quantified by lutein recovery) in RockstarTM at a concentration of 3 mg lutein / 473 mL of RockstarTM.
  • Microemulsion particle formulations showed superior stability performance characteristics as compared to OmniActiveTM Lutemax 2020 particle formulations after two weeks of storage in RockstarTM.
  • microemulsion particle formulations comprising lutein were characterized for lutein stability performance characteristics (as quantified by lutein recovery) in water at a concentration of 10 mg lutein / 10 mL of water. Microemulsion particle formulations showed desirable stability performance characteristics for a time period of up to 8 weeks storage in water.
  • microemulsion particle formulations comprising lutein were compared to OmniActiveTM Lutemax 2020 particle formulations (i.e., non-microemulsion particle formulations) for lutein stability performance characteristics (as quantified by lutein recovery) in water (FIG. 12A), oatmilk (FIG. 12B), and OatlyTM beverage (FIG. 12C) at a concentration of 1 mg lutein / 100 mL of each respective beverage.
  • Particle formulations mixed with water were stored at room temperature, while particle formulations mixed with oatmilk and OatlyTM beverage were stored at refrigerated temperatures (about 4 °C).
  • Microemulsion particle formulations showed desirable stability performance characteristics for a time period of up to 2 weeks storage in water, oatmilk, and OatlyTM beverage.
  • Vitamin D2 Recovery To evaluate the stability that microemulsion particle formulations provide to vitamin D2 as a payload component, 9.9 mL of a beverage was added to a 12 mL glass vial. 100 pL of a microemulsion formulation was then added to the 12 mL glass vial. The vial was covered with a rubber stopper and aluminum seal, crimped shut, and vortexed to ensure proper mixing. The contents of the vial were measured for vitamin D2 recovery in replicates of three at intervals of 0 days, 7 days, 14 days, 28 days, and 56 days. After each timepoint sample replicates were taken, sample vials were stored in a cardboard storage box at 25 °C until the next timepoint was measured.
  • the beverage layer was visibly separated from the bottom beverage layer and the top solvent layer.
  • About 0.54 mL of the top solvent layer was transferred into a 2 mL glass HPLC vial and capped.
  • Each replicate was then analyzed by HPLC to quantify the vitamin D2 in each sample by measuring the vitamin D peak area (mAU).
  • HPLC parameters used are presented in TABLE 3.
  • the average vitamin D peak area of the 3 replicates was then measured and used for quantifying vitamin D2 recovery.
  • the timepoint at 0 days was used as the basis for quantifying vitamin D2 recovery. Accordingly, vitamin D2 recovery was calculated as the percentage ratio of the average vitamin D2 peak area for each timepoint relative to the average vitamin D2 peak area at timepoint 0 days.
  • microemulsion particle formulations comprising vitamin D2 were assessed for vitamin D2 stability performance characteristics (as quantified by vitamin D2 recovery) and in water (FIG. 13A) and oatmilk (FIG. 13B) at a concentration of 1 .3 mg vitamin D2 / 100 mL of respective beverage.
  • performance characteristics were similarly assessed in a competitor product, exemplified by Provitas® D2-100SD formulation.
  • Particle formulations mixed with water were stored at room temperature, while particle formulations mixed with oatmilk were stored at refrigerated temperatures (about 4 °C).
  • Microemulsion particle formulations showed desirable stability performance characteristics for a time period of up to 2 weeks storage in water, oatmilk.
  • Vitamin Bl 2 Recovery To evaluate the stability that microemulsion particle formulations provide to vitamin B 12 as a payload component, 9.9 mL of a beverage was added to a 12 mL glass vial. 100 pL of a microemulsion formulation was then added to the 12 mL glass vial. The vial was covered with a rubber stopper and aluminum seal, crimped shut, and vortexed to ensure proper mixing. The contents of the vial were measured for vitamin B12 recovery in replicates of three at intervals of 0 days, 7 days, 14 days, 28 days, and 56 days. After each timepoint sample replicates were taken, sample vials were stored in a cardboard storage box at 25 °C until the next timepoint was measured.
  • the beverage layer was visibly separated from the top solvent layer and the bottom beverage layer.
  • About 0.5 mL of the bottom beverage layer was transferred into a 2 mL glass HPLC vial and capped.
  • Each replicate was then analyzed by HPLC to quantify the vitamin B12 in each sample by measuring the vitamin B 12 peak area (mAU).
  • HPLC parameters used are presented in TABLE 4.
  • the timepoint at 0 days was used as the basis for quantifying vitamin B12 recovery. Accordingly, vitamin B 12 recovery was calculated as the percentage ratio of the average vitamin B 12 peak area for each timepoint relative to the average vitamin B12 peak area at timepoint 0 days. TABLE 4.
  • microemulsion particle formulations comprising vitamin B12 were characterized for vitamin B12 stability performance characteristics (as quantified by vitamin B12 recovery) in water (FIG. 14A), oatmilk (FIG. 14B), and OatlyTM beverage (FIG. 14C) at a concentration of 0.2 mg vitamin B12 / 100 mL of respective beverage.
  • performance characteristics were similarly assessed in a competitor product, exemplified by DSMTM Vitamin B12 1% SD or CaldicTM 98% cyanocoblamin formulations.
  • exemplary microemulsion formulations as provided herein facilitate delayed release of payload components (e.g., caffeine) into solution.
  • payload components e.g., caffeine
  • Delayed release of caffeine has been a goal for the energy drink and carbonated beverage industries, among other things to reduce or avoid a caffeine “crash”.
  • certain phenolic acids specifically including those that include one or more gallic acid moieties, can bind to caffeine. Indeed, ability of phenols, polyphenols, and other agents (e.g., cyclodextrins) to complex with caffeine has been studies for decades (see, for example, Cai et al., J. Chem. Soc., Perkin Trans. 2:2197, 1990).
  • tannic-acid-based delayed-release caffeine preparations for inclusion in beverages, either as colloid preparations (see, for example, WO2022/266441) or as “emulsion” preparations (see, for example, WO2022/266442).
  • the present disclosure identifies the source of various problems with such studies and, moreover, provides microemulsion particle formulations, beverages containing them, and technologies for production and use of both, that achieve results not reported for other proposed extended-release caffeine formulations, including those described in WO2022/266441 and/or WO2022/266442.
  • Exemplary microemulsion formulations comprising caffeine were prepared according to methods disclosed herein.
  • microemulsion formulations comprising caffeine were prepared by a self- emulsification method.
  • Caffeine and tannic acid were separately weighed and separately dissolved in water and heated at 70 °C. After full dissolution of each of caffeine and tannic acid, the caffeine solution was added rapidly into the tannic acid solution to form a solution having a milky color, which is indicative of a tannic acid - caffeine complex forming.
  • a polysaccharide solution was also prepared by mixing a polysaccharide (e.g., xantham gum) in water. This polysaccharide solution was then mixed fully with the caffeine-tannic acid complex solution, forming an aqueous phase.
  • a mixture of an oil component e.g., soybean oil
  • a surfactant component e.g., polysorbate 80
  • a mixture of an oil component e.g., soybean oil
  • a surfactant component e.g., polysorbate 80
  • the oil phase was mixed with the aqueous phase at a ratio of oil phase to aqueous phase of about 1 :4 v/v by adding the aqueous phase into the oil phase in a dropwise manner while being stirred.
  • the mixture of oil phase and aqueous phase was stirred for at least 60 min to form a homogeneous suspension.
  • microemulsion particles are formed in a size range of 10-200 nm in diameter in monodispersed manner i.e., formulations were characterized as having low PDI).
  • Microemulsion particle formulation compositions of the present example are presented in TABLE 5.
  • exemplary microemulsion formulations of the present disclosure stored in Pepsi soft drink can delay payload component release to achieve sustained payload component bioavailability following ingestion of the formulation by a subject.

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Abstract

Les formulations de particules de microémulsion de l'invention peuvent être incluses dans des boissons, par exemple des boissons énergisantes. L'invention concerne des formulations de particules de microémulsion comprenant une ou plusieurs particules de microémulsion et une teneur élevée en eau, la ou les particules de microémulsion comprenant un composant de charge utile, un composant gras, un composant tensioactif, un composant antioxydant et un composant de stabilisation.
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WO2022266441A1 (fr) 2021-06-17 2022-12-22 Pepsico, Inc. Compositions permettant une libération lente de la caféine et boissons comprenant celles-ci
WO2022266442A1 (fr) 2021-06-17 2022-12-22 Pepsico, Inc. Compositions permettant une libération lente de la caféine

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EA201170897A1 (ru) * 2008-12-29 2011-12-30 Унилевер Н.В. Пищевые продукты, обогащенные метилксантинами

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022266441A1 (fr) 2021-06-17 2022-12-22 Pepsico, Inc. Compositions permettant une libération lente de la caféine et boissons comprenant celles-ci
WO2022266442A1 (fr) 2021-06-17 2022-12-22 Pepsico, Inc. Compositions permettant une libération lente de la caféine

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Title
CAI ET AL., J. CHEM. SOC., PERKIN TRANS., vol. 2000-2001, 1990, pages 2197

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