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WO2024010629A1 - Compositions et méthodes de traitement de l'hypertension - Google Patents

Compositions et méthodes de traitement de l'hypertension Download PDF

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Publication number
WO2024010629A1
WO2024010629A1 PCT/US2023/019789 US2023019789W WO2024010629A1 WO 2024010629 A1 WO2024010629 A1 WO 2024010629A1 US 2023019789 W US2023019789 W US 2023019789W WO 2024010629 A1 WO2024010629 A1 WO 2024010629A1
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WO
WIPO (PCT)
Prior art keywords
weight
oil
carriers
cbd
composition according
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.)
Ceased
Application number
PCT/US2023/019789
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English (en)
Inventor
John Docherty
Christopher Andrew BUNKO
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.)
Poviva Corp
Original Assignee
Poviva Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from US17/857,985 external-priority patent/US11666544B1/en
Priority claimed from US17/857,991 external-priority patent/US11980593B2/en
Application filed by Poviva Corp filed Critical Poviva Corp
Priority to MX2023011494A priority Critical patent/MX2023011494A/es
Priority to EP23723801.9A priority patent/EP4346802A4/fr
Priority to CA3199545A priority patent/CA3199545A1/fr
Priority to JP2023536335A priority patent/JP2024528761A/ja
Priority to AU2023237124A priority patent/AU2023237124A1/en
Publication of WO2024010629A1 publication Critical patent/WO2024010629A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23D—EDIBLE OILS OR FATS, e.g. MARGARINES, SHORTENINGS OR COOKING OILS
    • A23D7/00—Edible oil or fat compositions containing an aqueous phase, e.g. margarines
    • A23D7/005—Edible oil or fat compositions containing an aqueous phase, e.g. margarines characterised by ingredients other than fatty acid triglycerides
    • A23D7/0053—Compositions other than spreads
    • 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
    • A61K31/658—Medicinal preparations containing organic active ingredients o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/111—Aromatic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/158—Fatty acids; Fats; Products containing oils or fats
    • 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

Definitions

  • compositions and methods for delivering cannabidiol to a subject in need of hypertension treatment are orally delivered.
  • kits comprising the disclosed compositions as part of a method of delivering the cannabidiol-containing compositions.
  • Figure 1 is a plot of the individual plasma concentration of CBD in Animals 1-10 after oral administration of 25 mg/kg of the composition disclosed in Table 1.
  • Figure 2 is the plot of the average plasma concentrations of CBD in Animals 1-10 after oral administration of 25 mg/kg of the composition disclosed in Table 1.
  • Figure 3 is a plot of the individual plasma concentration of CBD in Animals 11-20 after oral administration of 25 mg/kg of the composition disclosed in Table 2.
  • Figure 4 is the plot of the average plasma concentrations of CBD in Animals 11-20 after oral administration of 25 mg/kg of the composition disclosed in Table 2.
  • Figure 5 is a plot of the individual plasma concentration of CBD in Animals 21-30 after oral administration of 25 mg/kg of the composition disclosed in Table 3.
  • Figure 6 is the plot of the average plasma concentrations of CBD in Animals 21-30 after oral administration of 25 mg/kg of the composition disclosed in Table 3.
  • Figure 7 is a plot of the individual plasma concentration of CBD in Animals 31-40 after oral administration of 25 mg/kg of the composition disclosed in Table 4.
  • Figure 8 is the plot of the average plasma concentrations of CBD in Animals 31-40 after oral administration of 25 mg/kg of the composition disclosed in Table 4.
  • Figure 9 is a plot of the individual plasma concentration of CBD in Animals 41-50 after oral administration of 25 mg/kg of the composition disclosed in Table 5.
  • Figure 10 is the plot of the average plasma concentrations of CBD in Animals 41-50 after oral administration of 25 mg/kg of the composition disclosed in Table 5.
  • Figure 11 is the 24-hour plot of the systolic blood pressure of subjects given the composition disclosed in Table 6 (•) versus placebo (o).
  • Figure 12 is the 24-hour plot of the mean arterial pressure of subjects given the composition disclosed in Table 6 (•) versus placebo (o).
  • Figure 13 is the 24-hour plot of the diastolic blood pressure of subjects given the composition disclosed in Table 6 (•) versus placebo (o).
  • Ranges may be expressed herein as from “about” one particular value, and/or to “about” another particular value. When such a range is expressed, another aspect includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint.
  • any embodiment of any of the disclosed methods or compositions can consist of or consist essentially of - rather than comprise/include/contain/have - any of the described steps, elements, and/or features.
  • the term “consisting of’ or “consisting essentially of’ can be substituted for any of the open-ended linking verbs recited above, in order to change the scope of a given claim from what it would otherwise be using the open-ended linking verb.
  • composition is defined herein as a composition that does not require approval by a regulatory authority and can be offered for sale by any retail merchant, for example, pharmacies, grocery stores, convenience stores, department stores, and the like.
  • any embodiment of any of the disclosed compounds or methods can consist of or consist essentially of - rather than comprise/include/contain/have - any of the described steps, elements, and/or features.
  • the term “consisting of’ or “consisting essentially of’ can be substituted for any of the open-ended linking verbs recited above, in order to change the scope of a given claim from what it would otherwise be using the open-ended linking verb.
  • compositions comprise:
  • the base compositions can comprise CBD oil.
  • CBD oil is the cannabidiol-containing extract from the hemp plant Cannabis sativa.
  • the CBD oil useful for preparing the disclosed compositions can be extracts which are crude extracts containing less than about 80% by weight of cannabidiol.
  • CBD oil comprising less than about 80% by weight of cannabidiol is referred to a “crude CBD oil.”
  • the formulator will necessarily adjust the amount of CBD oil present in the disclosed compositions to ensure adequate delivery of the desired amount of cannabidiol.
  • the compositions comprise a “hemp distillate” comprising from about 80% to about 92% by weight of cannabidiol.
  • cannabidiol in a still further embodiment isolated, pure cannabidiol can be used in the present compositions.
  • hemp distillate comprising from 80% to about 92% cannabidiol by weight
  • the term “CBD oil” applies. In some descriptions of the “CBD oil” this ingredient can be referred to as a “CBD resin.”
  • compositions comprise: a) from about 0.5% to about 20% by weight of CBD oil; b) from about 0.5% to about 60% by weight of one or more edible oils; and c) the balance a carrier.
  • the base compositions comprise: a) from about 0.5% to about 20% by weight of CBD oil; b) from about 0.5% to about 60% by weight of one or more edible oils; and c) the balance from about 20% to about 99% by weight of a carrier chosen from gum Arabic, inulin, microcrystalline cellulose, D-lactose monohydrate, quillaia, xanthan gum, pectin, guar, and psyllium.
  • a carrier chosen from gum Arabic, inulin, microcrystalline cellulose, D-lactose monohydrate, quillaia, xanthan gum, pectin, guar, and psyllium.
  • compositions comprise: a) from about 2% to about 5% by weight of CBD oil; b) from about 4% to about 15% by weight of sunflower oil; and c) a carrier chosen from gum Arabic, inulin, microcrystalline cellulose, D- lactose monohydrate, quillaia, xanthan gum, pectin, guar, and psyllium.
  • the base compositions comprise: a) from about 2% to about 5% by weight of CBD oil; b) from about 6% to about 15% by weight of sunflower oil; c) from about 5% to about 20% of a bile salt; and d) from about a carrier chosen from gum Arabic, inulin, microcrystalline cellulose, D-lactose monohydrate, and quillaia.
  • the carrier is gum Arabic.
  • the carrier is inulin.
  • the carrier is microcrystalline cellulose.
  • the carrier is D-lactose monohydrate.
  • the carrier is quillaia.
  • the base compositions comprise: a) from about 0.5% to about 8% by weight of CBD oil; b) from about 0.5% to about 15% by weight of coconut oil; and c) a carrier chosen from gum Arabic, inulin, microcrystalline cellulose, D- lactose monohydrate, quillaia, xanthan gum, pectin, guar, and psyllium.
  • the base compositions comprise: a) from about 2% to about 5% by weight of CBD oil; b) from about 4% to about 15% by weight of coconut oil; and c) a carrier chosen from gum Arabic, inulin, microcrystalline cellulose, D- lactose monohydrate, quillaia, xanthan gum, pectin, guar, and psyllium.
  • the base compositions comprise: a) from about 2% to about 5% by weight of CBD oil; b) from about 0.5% to about 15% by weight of coconut oil; c) from about 5% to about 15% of a bile salt; and d) a carrier chosen from gum Arabic, inulin, microcrystalline cellulose, D- lactose monohydrate, and quillaia.
  • the base composition comprises: a) from about 0.5% to about 8% by weight of CBD oil; b) from about 0.5% to about 15% by weight of coconut oil; and c) a carrier chosen from gum Arabic, inulin, microcrystalline cellulose, D- lactose monohydrate, quillaia, xanthan gum, pectin, guar, and psyllium.
  • the base compositions comprise: a) from about 0.5% to about 8% by weight of CBD oil; b) from about 0.5% to about 15% by weight of coconut oil; and c) a carrier chosen from gum Arabic, inulin, microcrystalline cellulose, D- lactose monohydrate, quillaia, xanthan gum, pectin, guar, and psyllium.
  • the base compositions comprise: a) from about 2% to about 5% by weight of CBD oil; b) from about 4% to about 15% by weight of coconut oil; and c) a carrier chosen from gum Arabic, inulin, microcrystalline cellulose, D- lactose monohydrate, quillaia, xanthan gum, pectin, guar, and psyllium.
  • the base compositions comprise: a) from about 2% to about 5% by weight of CBD oil; b) from about 0.5% to about 15% by weight of coconut oil; c) from about 5% to about 15% of a bile salt; and d) a carrier chosen from gum Arabic, inulin, microcrystalline cellulose, D- lactose monohydrate, and quillaia.
  • the disclosed compositions comprise from about 0.5% to about 20% by weight of CBD oil.
  • the disclosed base compositions can comprise from about 0.5% to about 8% by weight of CBD oil.
  • the base composition can comprise from about 1% to about 5% by weight of CBD oil.
  • the base composition can comprise from about 2% to about 6% by weight of CBD oil.
  • the base composition can comprise from about 2% to about 5% by weight of CBD oil.
  • the base composition can comprise from about 3% to about 5% by weight of CBD oil.
  • the amount of CBD oil can be 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, or 8% by weight or any fractional amounts, for example, 1.5%, 3,25%, and 5.75%.
  • a carboxylic acid in some embodiments aid in the formulation a flowable powder for encapsulation or packaging as described herein below, especially when the carboxylic acid serves to form a salt with one or more of the carriers or delivery agents.
  • the disclosed anti-hypertension compositions comprise: a) from about 5 mg to about 15 mg by weight of CBD oil; and b) from about 5 mg to about 45 mg by weight of one or more edible oils.
  • compositions comprise: a) from about 5 mg to about 15 mg by weight of CBD oil; b) from about 5 mg to about 45 mg by weight of one or more edible oils; and c) the balance one or more carriers.
  • compositions comprise: a) from about 5 mg to about 15 mg by weight of CBD oil; b) from about 5 mg to about 45 mg by weight of one or more edible oils; and c) from about 150 mg to about 500 mg by weight of one or more carriers.
  • compositions comprise: a) from about 5 mg to about 12 mg by weight of CBD oil; b) from about 5 mg to about 30 mg by weight of one or more edible oils; and c) from about 200 mg to about 350 mg by weight of one or more carriers.
  • compositions comprise: a) from about 7 mg to about 12 mg by weight of CBD oil; b) from about 7 mg to about 24 mg by weight of one or more edible oils; and c) from about 250 mg to about 350 mg by weight of one or more carriers.
  • compositions comprise: a) from about 5 mg to about 15 mg by weight of CBD oil; b) from about 5 mg to about 45 mg by weight of one or more edible oils; and c) from about 200 mg to about 350 mg by weight of one or more carriers chosen from gum Arabic, inulin, or mixtures thereof.
  • compositions comprise: a) from about 5 mg to about 15 mg by weight of CBD oil; b) from about 5 mg to about 45 mg by weight of one or more edible oils; c) from about 25 mg to about 45 mg by weight of one or more bile salts; and d) from about 200 mg to about 350 mg by weight of one or more carriers chosen from gum Arabic, inulin, or mixtures thereof.
  • compositions comprise: a) about 10 mg by weight of CBD oil; b) about 20 mg by weight of sunflower oil; c) about 34 mg by weight of ox bile; and c) about 278 mg by weight of gum Arabic.
  • compositions comprise: a) about 10 mg by weight of CBD oil; b) about 20 mg by weight of coconut oil; and c) about 240 mg by weight of inulin.
  • the composition comprises from about 5 mg to about 15 mg by weight of CBD oil.
  • the base compositions can comprise from about 5 mg to about 12 mg by weight of CBD oil.
  • the base compositions can comprise from about 7 mg to about 15 mg by weight of CBD oil.
  • the base compositions can comprise from about 7 mg to about 12 mg by weight of CBD oil.
  • the base compositions can comprise 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, or 15 mg by weight of CBD oil.
  • compositions comprise one or more edible oils.
  • the disclosed edible oils include oils that are primarily triglyceride-containing oils. Non-limiting examples of these oils are chosen from sunflower oil, coconut oil, canola oil, palm oil, soybean oil, com oil, safflower oil, and peanut oil.
  • the edible oil is sunflower oil. In a further nonlimiting example, the edible oil is coconut oil. In a still further non-limiting example, the edible oil is canola oil. In a yet further non-limiting example, the edible oil is palm oil. In a still yet non-limiting example, the edible oil is soybean oil. In another non-limiting example, the edible oil is com oil. In a still another non-limiting example the edible oil is safflower oil. In a yet another non-limiting example the edible oil is peanut oil.
  • the disclosed base compositions can comprise from about 0.5% to about 60% by weight of edible oil. In one embodiment the base compositions can comprise from about 3% to about 15% by weight of edible oil.
  • the base compositions can comprise from about 5% to about 17% by weight of edible oil. In a further embodiment the base compositions can comprise from about 7.5% to about 15% by weight of edible oil. In a still further embodiment, the base compositions can comprise from about 5% to about 10% by weight of edible oil. In a yet further embodiment, the compositions comprise from about 20% to about 40% by weight of one or more edible oils. In a still yet further embodiment, the compositions can comprise from about 15% to about 30% by weight of one or more edible oils.
  • compositions can comprise from about 0.5% to about 60% by weight of one or more edible oils, for example, the amount of edible oil can be 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 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%, or 60% by weight, or any fractional amount thereof, of one or more edible oils.
  • the ratio of CBD oil to edible oil is from about 1 : 1 to about 1 :4.
  • the ratio of CBD oil to edible oil can be 1 : 1, 1 : 1.1, 1 : 1.2, 1 : 1.3, 1 : 1.4, 1 : 1.5, 1 : 1.6, 1 : 1.7, 1 : 1.8, 1 : 1.9, 1 :2, 1 :2.1, 1 :2.2, 1 :2.3, 1 :2.4, 1 :2.5, 1 :2.6, 1 :2.7, 1 :2.8, 1 :2.9, or 1 :3.
  • the disclosed base compositions of this aspect comprise from about 5 mg to about 45 mg by weight of an edible oil.
  • the base compositions can comprise from about 5 mg to about 30 mg by weight of one or more edible oils.
  • the base compositions can comprise from about 5 mg to about 20 mg by weight of one or more edible oils.
  • the base compositions can comprise from about 5 mg to about 15 mg by weight of one or more edible oils.
  • the base compositions can comprise from about 5 mg to about 12 mg by weight of one or more edible oils.
  • the base compositions can comprise from about 10 mg to about 30 mg by weight of one or more edible oils.
  • the base compositions can comprise from about 15 mg to about 25 mg by weight of one or more edible oils.
  • compositions can comprise 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, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, or 45 mg by weight of one or more edible oils.
  • the disclosed edible oils include oils that are primarily triglyceride-containing oils. Ono-limiting examples of these oils are chosen from sunflower oil, coconut oil, canola oil, palm oil, soybean oil, corn oil, safflower oil, and peanut oil.
  • the edible oil is sunflower oil.
  • the edible oil is coconut oil.
  • the edible oil is canola oil.
  • the edible oil is palm oil.
  • the edible oil is soybean oil.
  • the edible oil is com oil.
  • the edible oil is safflower oil.
  • the edible oil is peanut oil.
  • highly unsaturated carboxylic acids derived from plant-based triglycerides can be mixed with one or more edible oils.
  • a formulator having a base composition comprising 10% by weight of an edible oil can substitute 5% of that edible oil with 5% of a disclosed carboxylic acid.
  • the disclosed carriers are polysaccharides.
  • Non-limiting examples of poly saccharide carriers include inulin, galactogen, cellulose, chitin, pectin, psyllium, guar, hemicellulose, potato starch, and partially hydrolyzed polysaccharides.
  • the carriers are sugar alcohols, for example, sorbitol, erythritol, xylitol, lactitol, maltitol, mannitol, hydrogenated starch hydrolysates, isomaltose, or any combination thereof.
  • carrier component is based on a native or chemically modified agar, alginates, carrageenan gum, cellulose, chitosan, chitin, cyclodextrin, dextran, gellan gum, glycogen, glycosaminoglycan, gum karaya, inulin, pectin, polydextrose, xanthan gum, or any other starches, gums or other polysaccharide, including functionalized derivatives, dextrinized, hydrolyzed, oxidized, alkylated, hydroxyalkylated, acetylated, fractionated, and physically modified starches and mixtures thereof.
  • glycerin and/or propylene glycol can be added as a carrier.
  • the carrier is chosen from gum Arabic, inulin, mannitol, silicon dioxide, colloidal silicon dioxide, microcrystalline cellulose, D-lactose monohydrate, tapioca starch, tapioca flour, quillaia, or mixtures thereof.
  • the carrier is gum Arabic.
  • the carrier is inulin.
  • the carrier is microcrystalline cellulose.
  • the carrier is D-lactose monohydrate.
  • the carrier is quillaia.
  • the carrier can be a combination of gum Arabic, inulin, microcrystalline cellulose, D-lactose monohydrate, or quillaia.
  • the carrier is mannitol, a non-limiting example is PartekTM mannitol, available from Partek Inc.
  • the carrier is a microcrystalline cellulose.
  • the carrier is colloidal silicon dioxide.
  • the disclosed base compositions can comprise from about 50% to about 99% by weight of one or more carriers. In one embodiment disclosed compositions can comprise from about 60% to about 95% by weight of one or more carriers. In another embodiment the disclosed compositions can comprise from about 60% to about 80% by weight of one or more carriers. In a yet another embodiment the disclosed compositions can comprise from about 75% to about 95% by weight of one or more carriers. In a further embodiment the disclosed compositions can comprise from about 65% to about 90% by weight of one or more carriers. As such, the disclosed base compositions can comprise 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%,
  • the disclosed base compositions can comprise from about 100 mg to about 500 mg by weight of one or more carriers. In one embodiment the base compositions comprise from about 250 mg to about 350 mg by weight of one or more carriers. In another embodiment the base compositions comprise from about 150 mg to about 300 mg by weight of one or more carriers. In a further embodiment the base compositions comprise from about 200 mg to about 300 mg by weight of one or more carriers. In a yet further embodiment the base compositions comprise from about 300 mg to about 400 mg by weight of one or more carriers. In one embodiment the base compositions comprise from about 200 mg to about 450 mg by weight of one or more carriers.
  • the disclosed base compositions can comprise 100 mg, 101 mg, 102, mg, 103, mg, 104 mg, 105 mg, 106 mg, 107 mg, 108 mg, 109 mg, 110 mg, 111 mg, 112 mg, 113 mg, 114 mg, 115 mg, 116 mg, 117 mg, 118 mg, 119 mg, 120 mg, 121 mg, 122 mg, 123 mg, 124 mg, 125 mg, 126 mg, 127 mg,
  • Bile Salts The disclosed base compositions can further comprise from 5% to about 20% by weight of a bile salt.
  • Bile salts enhance the ability of the disclosed compositions to target the duodenum.
  • Non-limiting examples of bile salts and/or bile acids includes steroid acids (and/or the carboxylate anion thereof) and salts thereof, found in the bile of an animal (e.g., a human), including cholic acid, cholate, deoxycholic acid, deoxycholate, hyodeoxycholic acid, hyodeoxycholate, glycocholic acid, glycocholate, taurocholic acid, taurocholate, chenodeoxycholic acid, chenodeoxycholate, lithocholic acid, lithocolate, and the like.
  • Taurocholic acid and/or taurocholate are referred to herein as TCA.
  • Bile salts are typically conjugated with glycine or taurine.
  • the term "bile acid” as used herein includes cholic acid conjugated with either glycine or taurine: glycocholate and taurocholate, respectively (and salts thereof). Any reference to a bile salt or bile acid used herein includes reference to an identical compound naturally or synthetically prepared. In one non-limiting example the bile salt is ox bile.
  • compositions can comprise from about 5% to about 20% by weight of one or more bile salts. In one embodiment the compositions comprise from about 7.5% to about 20% by weight of one or more bile salts. In one embodiment the compositions comprise from about 7.5% to about 12.5% by weight of one or more bile salts. In one embodiment the compositions comprise from about 15% to about 20% by weight of one or more bile salts. In one embodiment the compositions comprise from about 5% to about 15% by weight of one or more bile salts. In one embodiment the compositions comprise from about 12% to about 15% by weight of one or more bile salts.
  • compositions can comprise, for example, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20 % by weight of one or more bile salts.
  • compositions comprise from about 25 mg to about 50 mg by weight of one or mor bile salts. In one embodiment, the compositions comprise from about 30 mg to about 50 mg by weight of one or more bile salts. In another embodiment, the compositions comprise from about 30 mg to about 40 mg by weight of one or more bile salts. In further embodiment, the compositions comprise from about 25 mg to about 40 mg by weight of one or more bile salts. In yet another embodiment, the compositions comprise from about 25 mg to about 35 mg by weight of one or more bile salts.
  • the disclosed base compositions can comprise, for example, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, 30 mg 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, or 50 mg by weight one or more bile salts.
  • composition comprises: a) from about 10 mg to about 100 mg by weight of CBD oil; b) from about 10 mg to about 300 mg by weight of sunflower oil; and c) the balance one or more carriers.
  • the base composition comprises: a) from about 10 mg to about 100 mg by weight of CBD oil; b) from about 10 mg to about 300 mg by weight of sunflower oil; and c) from about 200 mg to about 800 mg by weight of one or more carriers.
  • the base compositions comprise: a) from about 10 mg to about 100 mg by weight of CBD oil; b) from about 10 mg to about 300 mg by weight of sunflower oil; c) from about 50 mg to about 8 mg by weight of one or more bile salts; and d) from about 200 mg to about 800 mg by weight of one or more carriers.
  • the base compositions comprise: a) from about 10 mg to about 100 mg by weight of CBD oil; b) from about 10 mg to about 300 mg by weight of sunflower oil; c) from about 50 mg to about 80 mg by weight of one or more bile salts; and d) from about 200 mg to about 800 mg by weight of one or more carriers wherein the carriers are chosen from tapioca starch, tapioca flour, silicon dioxide, and mixture thereof.
  • the base compositions comprise: a) from about 25 mg to about 40 mg by weight of CBD oil; b) from about 50 mg to about 80 mg by weight of sunflower oil; c) from about 60 mg to about 70 mg by weight of one or more bile salts; and d) from about 500 mg to about 600 mg by weight of one or more carriers wherein the carriers are chosen from tapioca starch, tapioca flour, silicon dioxide, and mixture thereof.
  • the base compositions comprise: a) from about 75 mg to about 90 mg by weight of CBD oil; b) from about 55 mg to about 70 mg by weight of sunflower oil; c) from about 60 mg to about 70 mg by weight of one or more bile salts; and d) from about 500 mg to about 600 mg by weight of one or more carriers wherein the carriers are chosen from tapioca starch, tapioca flour, silicon dioxide, and mixture thereof.
  • the base compositions comprise: a) about 81 mg by weight of CBD oil; b) about 62 mg by weight of sunflower oil; c) about 65 mg by weight of one or more bile salts; and d) about 575 mg by weight of one or more carriers wherein the carriers are chosen from tapioca starch, tapioca flour, silicon dioxide, and mixture thereof.
  • the base composition comprises: a) from about 20 mg to about 40 mg by weight of CBD oil; b) from about 40 mg to about 80 mg by weight of sunflower oil; and c) from about 500 mg to about 600 mg by weight of one or more carriers.
  • the base composition comprises: a) from about 70 mg to about 100 mg by weight of CBD oil; b) from about 70 mg to about 200 mg by weight of sunflower oil; and c) from about 300 mg to about 450 mg by weight of one or more carriers.
  • the base composition comprises: a) from about 70 mg to about 100 mg by weight of CBD oil; b) from about 70 mg to about 200 mg by weight of sunflower oil; and c) from about 300 mg to about 450 mg by weight of one or more carriers wherein the carriers are chosen from mannitol, silicon dioxide, colloidal silicon dioxide, microcrystalline cellulose, and mixture thereof.
  • the base compositions comprise: a) from about 80 mg to about 95 mg by weight of CBD oil; b) from about 160 mg to about 190 mg by weight of sunflower oil; and c) from about 300 mg to about 400 mg by weight of one or more carriers wherein the carriers are chosen from mannitol, silicon dioxide, colloidal silicon dioxide, microcrystalline cellulose, and mixture thereof.
  • the base compositions comprise: a) from about 80 mg to about 95 mg by weight of CBD oil; b) from about 160 mg to about 190 mg by weight of sunflower oil; c) from about 60 mg to about 70 mg by weight of one or more bile salts and d) from about 300 mg to about 400 mg by weight of one or more carriers wherein the carriers are chosen from mannitol, silicon dioxide, colloidal silicon dioxide, microcrystalline cellulose, and mixture thereof.
  • the base compositions comprise: a) about 87 mg by weight of CBD oil; b) about 174 mg by weight of sunflower oil; c) about 65 mg by weight one or more bile salts; and d) about 375 mg by weight of one or more carriers wherein the carriers are chosen from mannitol, silicon dioxide, colloidal silicon dioxide, microcrystalline cellulose.
  • the base composition comprises: a) from about 65 mg to about 85 mg by weight of CBD oil; b) from about 135 mg to about 170 mg by weight of sunflower oil; and c) from about 300 mg to about 400 mg by weight of one or more carriers.
  • the base composition comprises: a) from about 65 mg to about 85 mg by weight of CBD oil; b) from about 135 mg to about 170 mg by weight of sunflower oil; and c) from about 300 mg to about 400 mg by weight of one or more carriers wherein the carriers are chosen from mannitol, silicon dioxide, colloidal silicon dioxide, microcrystalline cellulose, and mixture thereof.
  • the base composition comprises: a) from about 70 mg to about 80 mg by weight of CBD oil; b) from about 145 mg to about 160 mg by weight of sunflower oil; and c) from about 300 mg to about 350 mg by weight of one or more carriers wherein the carriers are chosen from mannitol, silicon dioxide, colloidal silicon dioxide, microcrystalline cellulose, and mixture thereof.
  • the base composition comprises: a) from about 70 mg to about 80 mg by weight of CBD oil; b) from about 145 mg to about 160 mg by weight of sunflower oil; c) from about 5 mg to about 8 mg by weight of one or more bile salts; and d) from about 300 mg to about 350 mg by weight of one or more carriers wherein the carriers are chosen mannitol, silicon dioxide, colloidal silicon dioxide, microcrystalline cellulose, and mixture thereof.
  • the base composition comprises: a) about 76 mg by weight of CBD oil; b) about 152 mg by weight of sunflower oil; c) about 7 mg by weight of one or more bile salts; and d) about 335 mg by weight of one or more carriers wherein the carriers are chosen from mannitol, silicon dioxide, colloidal silicon dioxide, microcrystalline cellulose, and mixture thereof.
  • a base composition comprises: a) from about 5 mg to about 15 mg by weight of CBD oil; b) from about 5 mg to about 60 mg by weight of an admixture of a carboxylic acid derived from a plant-based triglyceride and one or more edible oils, wherein the ratio of the carboxylic acid and the edible oils is from about 1 :9 to about 9: 1; and c) from about 100 mg to about 300 mg by weight of one or more carriers.
  • compositions are free flowing solids.
  • the disclosed compositions have less than about 0.01% by weight of moisture. Any residual moisture can be removed by standard dehydration processes.
  • free flowing solids the compositions can readily be placed into capsules, made into tablets or pellets. If the formulator wishes to form a liquid composition, the compositions can be dissolved in or suspended in a carrier.
  • compositions suitable forms for delivery of the disclosed compositions: Sublingual tablets, buccal tablets, orally-disintegrating tablets, chewable tablets, lozenges, oral powders, oral granules, oral pellets, chewable gels, granules of pellets intended for reconstitution in a liquid medium for immediate consumption, hard candy, gelatin based chewy candy, gummy candies, jelly candies, sprinkle formulation, swallowable immediate- release capsules, pills or tablets, extended-release capsules, pills or tablets, or delayed- release capsules, pill or tablets.
  • a total dosage of the disclosed composition is from about 90 mg to about 450 mg over the course of 24 hours depending upon the severity of the hypertension. For an average hum weighing 60 kg, this equates to from about 1.5 mg/kg to about 75 mg/kg per 24 hours.
  • the dosage per day is from about 90 mg to about 150 mg. In a further embodiment the dosage per day is from about 140 mg to about 250 mg. In another embodiment the dosage per day is from about 200 mg to about 400 mg. In a still further embodiment the dosage per day is from about 300 mg to about 450 mg. In a yet further embodiment the dosage per day is from about 250 mg to about 350 mg.
  • the dosage of one or more disclosed compositions can be from about 90 mg to about 450 mg per 24 hours, for example, 90 mg, 91 mg, 92 mg, 93 mg, 94 mg, 95 mg, 96 mg, 97 mg, 98 mg, 99 mg, 100 mg, 101 mg, 102, mg, 103, mg, 104 mg, 105 mg, 106 mg, 107 mg, 108 mg, 109 mg, 110 mg, 111 mg, 112 mg, 113 mg, 114 mg, 115 mg, 116 mg, 117 mg, 118 mg, 119 mg, 120 mg, 121 mg, 122 mg, 123 mg, 124 mg, 125 mg, 126 mg, 127 mg, 128 mg, 129 mg, 130 mg 31 mg, 132 mg, 133 mg, 134 mg, 135 mg, 136 mg, 137 mg, 138 mg, 139 mg, 140 mg, 141 mg, 142 mg, 143 mg, 144 mg, 145 mg, 146 mg, 147 mg, 148 mg,
  • Parteck-M® 100 mannitol (80.62 g) was added to the reaction mixture smith continuous stirring at 75 °C. The contents of the vessel was spread evenly on a dehydrator tray and the tray was then placed in a convection air flow dehydrator at about 65 °C for 90 minutes. The trays were then allowed to cool to room temperature. The dehydrated admixture was transferred to stainless-steel vessel and deoxycholic acid (3.86 g) was added with continuous stirring until the admixture was homogeneous. The yield was of the total product was approximately 309 g.
  • the composition for testing was formed into capsules having the quantities disclosed in Table 1
  • CBD oil (10 g) and sunflower oil (10 g) is combined with 100 g of D-lactose monohydrate to form a homogeneous admixture.
  • the admixture is then metered into 212.5 gm of quillaja in 467.5 mL of water to form a pre-emulsion.
  • the pre-emulsion is then passed through a high pressure microfluidizer homogenizer to afford the liquid nanoemulsion.
  • TABLE XIX provides the mean and standard deviation for the results of Animals-30.
  • TABLE XII provides the mean and standard deviation for the results of Animals-40.
  • TABLE XV provides the mean and standard deviation for the results of Animals-50.
  • compositions were used in controlled human clinical trials measuring the difference in systolic blood pressure (SBP), mean arterial pressure (MSP), and diastolic blood pressure (DBP) between volunteers taking a composition disclosed in Table 6 or Table 7 versus placebo over a 24 hour period.
  • SBP systolic blood pressure
  • MSP mean arterial pressure
  • DBP diastolic blood pressure
  • cannabidiol for an effective amount of 25 mg. contains 45-55% deoxycholic acid, taurocholate and glycocholic acid
  • TABLE 7 contains 90.64 % cannabidiol for an effective amount of 75 mg. contains 45-55% deoxycholic acid, taurocholate and glycocholic acid
  • Table 8 The composition disclosed in Table 8 is used for a human clinical trial.
  • composition disclosed in Table 6 was administered to human volunteers with mild to moderate hypertension under the following protocol.
  • the results are depicted in Figure 11.
  • the results of subjects given the composition containing the composition in Table 6 are reflected in the dashed line with solid circles (•) and the subjects given the placebo are reflected in the solid line and open circles (o).
  • SBP systolic blood pressure
  • Figure 12 reflects the mean arterial pressures (MAP) of the two groups. During the ambulatory period, volunteers averaged a significant reduction of 5.3% in MAP versus the group given a placebo.
  • Figure 13 reflects the reduction of 3.5% in diastolic pressure versus placebo.
  • Arterial stiffness is a strong predictor of disease in humans.
  • the impacts of increased arterial stiffness are not limited only to coronary heart disease such as hypertension, but also include other disease states such as diabetes mellitus, renal disease and more. It can also be a prognostic marker for cardiovascular events and all -cause mortality, even in asymptomatic individuals without overt cardiovascular disease.
  • This study is more comprehensive than the study conducted above and many types of analysis are performed including 24-hour ambulatory blood pressure (which is the primary outcome); arterial stiffness and autonomic balance; brain structure and function through brain magnetic resonance imaging (“MRI”); blood biomarkers (including lipids such as cholesterol and more); renal, hepatic, sleep quality / daytime sleepiness / sleep disorders; actigraphy, geriatric depression scale, perceived stress, and Beck anxiety inventory.
  • MRI brain magnetic resonance imaging
  • biomarkers including lipids such as cholesterol and more
  • actigraphy geriatric depression scale, perceived stress, and Beck anxiety inventory.

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Abstract

Sont divulguées dans la présente invention des compositions et des méthodes d'administration de cannabidiol à un sujet dont l'état le nécessite. Les compositions divulguées comprenant de l'huile de CBD, de l'huile comestible et un transporteur sont administrées par voie orale pour le traitement de l'hypertension. Sont également divulgués des kits comprenant les compositions divulguées dans le cadre d'un procédé d'administration de la composition contenant du cannabidiol.
PCT/US2023/019789 2022-07-05 2023-04-25 Compositions et méthodes de traitement de l'hypertension Ceased WO2024010629A1 (fr)

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MX2023011494A MX2023011494A (es) 2022-07-05 2023-04-25 Composiciones y metodos para el tratamiento de la hipertension.
EP23723801.9A EP4346802A4 (fr) 2022-07-05 2023-04-25 Compositions et méthodes de traitement de l'hypertension
CA3199545A CA3199545A1 (fr) 2022-07-05 2023-04-25 Compositions et methodes pour le traitement de l'hypertension
JP2023536335A JP2024528761A (ja) 2022-07-05 2023-04-25 高血圧を処置する為の組成物及び方法
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WO2020236802A1 (fr) * 2019-05-20 2020-11-26 Poviva Corp. Compositions comprenant des agents biologiquement actifs et des sels biliaires
US20210177978A1 (en) * 2015-12-09 2021-06-17 Poviva Corp. Methods for formulating orally ingestible compositions comprising lipophilic active agents

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US20200315965A1 (en) * 2019-04-02 2020-10-08 Cannasol Technologies, Llc Nanoemulsion concentrate formulations and methods
JP2021031485A (ja) * 2020-02-06 2021-03-01 株式会社中島商会 Ｃｂｄオイルの製造方法
US20210299062A1 (en) * 2020-03-29 2021-09-30 Mark J. Rosenfeld Cannabinoid compositions and methods of treatment
WO2021216475A1 (fr) * 2020-04-20 2021-10-28 Poviva Corp. Compositions et méthodes permettant une administration améliorée d'agents antiviraux
CN114177163B (zh) * 2022-01-12 2023-05-02 刘树民 一种治疗高血压的药物

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US20210177978A1 (en) * 2015-12-09 2021-06-17 Poviva Corp. Methods for formulating orally ingestible compositions comprising lipophilic active agents
US20200188322A1 (en) * 2017-07-18 2020-06-18 Deyi Pharmarmaceutical Ltd. Use of cannabidiol in treatment of pulmonary hypertension
WO2020236802A1 (fr) * 2019-05-20 2020-11-26 Poviva Corp. Compositions comprenant des agents biologiquement actifs et des sels biliaires

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