methods and compositions to improve health conditions

专利摘要:
compositions, methods, and kits described herein can be formulated as a nutritional supplement or a dietary supplement. a composition described herein can provide nutrients or compounds that may otherwise not be consumed in sufficient quantities in a normal diet, and can contribute to an individual's physical and emotional well-being.
公开号:BR112019020554A2
申请号:R112019020554
申请日:2018-03-23
公开日:2020-04-28
发明作者:William Kleidon
申请人:Ojai Energetics Pbc；
IPC主号:

专利说明:

Invention Patent Descriptive Report for “METHODS AND COMPOSITIONS TO IMPROVE HEALTH CONDITIONS”.
CROSS REFERENCE [0001] This application claims priority to United States Provisional Patent Application Serial No. 62 / 479,091, filed on March 30, 2017, United States Provisional Patent Application Serial No. 62 / 506,475, filed on May 15, 2017, and United States Provisional Patent Application Serial No. 62 / 632,965, filed on February 20, 2018, each of which is incorporated herein by reference.
BACKGROUND [0002] Terpenoids are compounds that can have beneficial effects on an individual when taken as a nutritional supplement or a dietary supplement. Terpenoids can have health benefits, physical well-being, and / or emotional well-being for an individual.
[0003] Terpenoids can be used to treat or lessen symptoms of a number of classes of disorders, such as anti-inflammatory disorders, psychiatric disorders, and sleep disorders. Terpenoid degradation compounds can be formed as a by-product during the manufacture of a composition comprising terpenoids. Terpenoid degradation compounds may have little benefit, no effect, or harmful effects on an individual.
SUMMARY [0004] In one aspect, the present disclosure provides a unit dose comprising: (i) a mixture of carboxylated cannabinoids and decarboxylated cannabinoids, and (ii) one or more terpenoids, in which a weight / weight ratio of decarboxylated cannabinoids to carboxylated cannabinoids is greater than 0.5, and in which the
Petition 870190097797, of 9/30/2019, p. 9/284
2/68 unit dose is substantially free of terpenoid degrading compounds. In some embodiments, the unit dose comprises at least 5 mg of decarboxylated cannabinoids. In some embodiments, decarboxylated cannabinoids comprise Δ ⁹ tetrahydrocannabinol.
[0005] In some embodiments, one or more terpenoids is selected from the group consisting of: mircene, limonene, linalool, trans-ocimene, òefa-pinene, a / fa-pinene, eta-carlophylene, delta ~ 3 ~ carene, trans-gamma-bisabolene, trans-a / fa-farnesene, befa-fenchol, a / fa-humulene, and guajol · In some embodiments, one or more terpenoid degrading compounds are selected from the group consisting of: geraniol, geranyl isobutyrate, p-clenene, p-cymene, pmenta-1,5,8-triene, carvone, 3-methyl-6- (1 - methylethylidene) - 2 - cyclohexen ·· 1 ~ one, 3-metH -6 “(1 ~ methyletenll) ~ 2 ~ cyclohexen-1 -one, eucarvone, thymol, p-mint-1 (7), 8-dien-2-ol, perylyl alcohol, camphene, befa-myrcene, alphanelandian, a / fa-terpinene, gamma-terpinene, terpinolene, 4-hydroxy-2methyl-2-cyclohexenone, p ~ cimenene, o-cymene, 3 ~ caren ~ 2 ~ one, 3-caren ~ 5-one, 3-carene oxide , 3-careno-2,5-dione, trans-2-hydroxy ~ 3 ~ caren5-one, thymol, carvacrol, 1,4-cineole, eucalyptol, 3- (1-methylethyl) -6-oxo-2heptenai, and 3,7-dimethyl6 ~ oxo ~ 2 ~ octenai. In some embodiments, the unit dose additionally comprises a trace amount of an acid. In some embodiments, the unit dose additionally comprises a pharmaceutically acceptable exciplent.
[0006] In some embodiments, the pharmaceutically acceptable exciplente is selected from the group consisting of: a binder, a filler, a plasticizer, a lubricant, an anti-foaming agent, a buffering agent, a polymer, an antioxidant, a preservative, a chelating agent, a flavoring, a dye, an odoriferous, a suspending agent, and a combination thereof. In some embodiments, the unit dose is formulated to
Petition 870190097797, of 9/30/2019, p. 10/284
3/68 oral, topical, inhalation, intravenous, or intramuscular administration. In some embodiments, the unit dose is in a solid form. In some embodiments, the unit dose is in a liquid form. In some embodiments, the unit dose is a tablet, a chewable tablet, a capsule, a pill, a granule, an emulsion, a gel, a spray, a plurality of spheres encapsulated in a capsule, a powder, a suspension, a solution liquid, a semi-liquid solution, a semi-solid solution, a syrup, or a slurry. In some embodiments, the unit dose retains at least 80% of the cannabinoids after being placed in a sealed container for 6 months at a temperature of around 25 ° C and a relative humidity level of about 50%. In some embodiments, the unit dose is packaged in a container selected from the group consisting of a tube, a jar, a box, a bottle, a bag, a tray, a drum, a bottle, a syringe, and a can. In some embodiments, a kit comprises a unit dose disclosed herein and instructions for supplementing the mixture of carboxylated cannabinoids and decarboxylated cannabinoids, and one or more terpenoids to an individual in need thereof.
[0007] In one aspect, the present disclosure provides a kit for preparing Δ ⁹ tetrahydrocannabinol comprising: (i) an acid present in an effective amount for converting at least 50% of tetrahydrocannabinolic acid to Δ ⁹ tetrahydrocannabinol, (ii) an reaction vessel configured to retain a reaction mixture comprising acid and tetrahydrocannabinolic acid, and (iii) instructions for performing the conversion using the acid. In some embodiments, the kit additionally comprises tetrahydrocannabinolic acid. In some embodiments, the acid is a weak acid. In some embodiments, the acid has a pKa of about 3 to about
7.
Petition 870190097797, of 9/30/2019, p. 11/284
4/68 [0008] In some embodiments, the acid is selected from the group consisting of: lactic acid, citric acid, malic acid, acetic acid, benzoic acid, ascorbic acid, tartaric acid, and oxalic acid.
[0009] In one aspect, the present disclosure provides a method of supplementing one or more cannabinoids and one or more terpenoids to an individual in need thereof, the method comprising administering to the individual a unit dose comprising: a mixture of carboxylated cannabinoids and decarboxylated cannabinoids , and one or more terpenoids, in which a weight / weight ratio of decarboxylated cannabinoids to carboxylated cannabinoids is greater than 0.5, and in which the unit dose is substantially free of terpenoid degrading compounds. In some embodiments, the individual suffers from a symptom selected from the group consisting of: pain, stress, nausea, vomiting, insomnia, anxiety, and loss of appetite. In some embodiments, the unit dose is administered orally, topically, by inhalation, intravenously, or intramuscularly. In some embodiments, the unit dose is administered at least once a day. In some embodiments, the method further comprises monitoring an individual's health status or condition following administration of the unit dose to the individual.
[0010] In one aspect, the present disclosure provides a method of supplementing one or more cannabinoids and one or more terpenoids to an individual in need thereof, the method comprising administering to the individual a unit dose disclosed herein. In some embodiments, the individual suffers from a symptom selected from the group consisting of: pain, stress, nausea, vomiting, insomnia, anxiety, and loss of appetite. In some embodiments, the unit dose is administered orally, topically, by inhalation, intrave
Petition 870190097797, of 9/30/2019, p. 12/284
5/68 nosy, or intramuscularly. In some embodiments, the unit dose is administered at least once a day. A unit dose can be administered intravenously to an individual before, during, or after a surgical procedure (for example, within 1 minute, 10 minutes, 20 minutes or 30 minutes after surgery).
[0011] In one aspect, the present disclosure provides a method of producing decarboxylated cannabinoids, comprising: (i) contacting a cannabis plant or a portion thereof with an acid to form a reaction mixture under effective conditions for converting carboxylated cannabinoids present in the cannabis plant for decarboxylated cannabinoids; and (ii) separating the cannabis plant or a portion of it from decarboxylated cannabinoids, thereby producing decarboxylated cannabinoids. In some embodiments, the decarboxylated cannabinoids comprise Δ ⁹ tetrahydrocannabinoi. In some embodiments, a weight / weight ratio of decarboxylated cannabinoids to carboxylated cannabinoids in the reaction mixture of (ii) is greater than 0.1. In some embodiments, the conditions are at a temperature of less than 300 ° C. In some embodiments, external heating is not applied during the conversion of carboxylated cannabinoids to decarboxylated cannabinoids. In some embodiments, the acid is a weak acid. In some embodiments, the contact comprises mixing, mixing, stirring, or a combination of these. In some embodiments, the separation is selected from the group consisting of: filtration, extraction, centrifugation, solubilization, concentration, washing, electrolysis, adsorption, purification, chromatography, fractionation, crystallization, and a combination of these.
[0012] In another aspect, the present disclosure provides a mixture comprising: (i) carboxylated cannabinoids and decarboxylated cannabinoids, (ii) one or more terpenoids, and (iii) an acid, in the
Petition 870190097797, of 9/30/2019, p. 13/284
6/68 which a weight / weight ratio of decarboxylated cannabinoids to carboxylated cannabinoids is greater than 0.1, and in which the acid is present in an effective amount in converting at least a portion of carboxylated cannabinoids to decarboxylated cannabinoids. In some embodiments, carboxylated cannabinoids comprise tetrahydrocannabinolic acid. In some embodiments, the mixture comprises at least 0.05% of the decarboxylated cannabinoids. In some embodiments, the decarboxylated cannabinoids comprise Δ ⁹ tetrahydrocannabinol. In some embodiments, a weight / weight ratio of Δ ⁹ tetrahydrocannabinol to tetrahydrocannabinolic acid is greater than about 0.1. In some embodiments, the mixture is substantially free of terpenoid degrading compounds. In some embodiments, the acid is an organic acid.
[0013] In one aspect, the present disclosure provides a reaction vessel comprising a mixture disclosed herein, in which the reaction vessel is configured to provide production of at least 10 g of the decarboxylated cannabinoids.
[0014] In one aspect, the present disclosure provides a method for generating a decarboxylated cannabinoid formulation, comprising: providing a reaction vessel comprising a mixture, in which the mixture comprises: carboxylated cannabinoids and decarboxylated cannabinoids, one or more terpenoids, and an acid, in which a weight / weight ratio of decarboxylated cannabinoids to carboxylated cannabinoids is greater than 0.1, and in which the acid is present in an effective amount in converting at least a portion of carboxylated cannabinoids to decarboxylated cannabinoids ; and mixing the mixture to produce the decarboxylated cannabinoid formulation. In some embodiments, the decarboxylated cannabinoid formulation comprises at least
Petition 870190097797, of 9/30/2019, p. 14/284
7/68 minus 5 mg of decarboxylated cannabinoids. In some embodiments, the decarboxylated cannabinoid formulation comprises Δ ⁹ tetrahydrocannabinol. In some embodiments, the one or more terpenoids is selected from the group consisting of: myrcene, IImonene, linalool, trans-ocimene, beia-pinene, a / fa-pinin, beta-carotene, delta-3-carene, trans-gamma- bisabolene, trans-a / fafarnesene, beta-fenchol, a / fa-humulene, and guajol. In some embodiments, the acid is a weak acid. In some embodiments, the acid has a pKa of about 3 to about 7. In some embodiments, the acid is selected from the group consisting of: lactic acid, citric acid, malic acid, acetic acid, benzoic acid, ascorbic acid , tartaric acid, and oxalic acid.
[0015] In one aspect, the present disclosure provides a unit dose comprising: a mixture of carboxylated cannabinoids and decarboxylated cannabinoids, and one or more terpenoids, in which a weight / weight ratio of decarboxylated cannabinoids to carboxylated cannabinoids is greater than 0 , 5, in which the unit dose is substantially free of terpenoid degrading compounds, and in which the unit dose is substantially free of an acid. In some embodiments, the acid is a weak acid. In some embodiments, the acid has a pKa of about 3 to about 7. In some embodiments, the acid is selected from the group consisting of: lactic acid, citric acid, malic acid, acetic acid, benzoic acid, ascorbic acid , tartaric acid, and oxalic acid.
[0016] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description, in which only illustrative embodiments of the present disclosure are shown and described. As will be understood, the present revelation is capable of other and different embodiments, and its various details are capable of modifying
Petition 870190097797, of 9/30/2019, p. 15/284
8/68 cations in several obvious aspects, all without escaping the revelation. Consequently, the drawings and description are to be listed as illustrative in nature, and not as restrictive.
INCORPORATION BY REFERENCE [0017] All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference in the same proportion as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference . Since publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to replace and / or take precedence over any such contradictory material.
BRIEF DESCRIPTION OF THE DRAWINGS [0018] The new features of the invention are placed with particularity in the appended claims. A better understanding of the characteristics and advantages of the present invention will be obtained by reference to the following detailed description that places illustrative embodiments, in which the principles of the invention are used, and the accompanying drawings (also "Figure" and "FIG." Here), of the which: [0019] FIG. 1 shows a computer control system that is programmed or otherwise configured to implement methods provided herein.
DETAILED DESCRIPTION [0020] While various embodiments of the invention have been shown and described here, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions can occur to those skilled in the art without evading invention. It should be understood that several alternatives to the embodiments of the invention here
Petition 870190097797, of 9/30/2019, p. 16/284
9/68 described can be used.
[0021] The term "about", as used herein, generally refers to an acceptable error range for the particular value as determined by a person skilled in the art, which may depend in part on how the value is measured or determined. For example, "about" can mean within 1 or more than 1 standard deviation. Alternatively, "about" can mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. Alternatively, particularly in relation to biological systems or processes, the term can mean within an order of magnitude, within 5 times, and within 2 times, within a value.
[0022] The term "individual", as used here, generally refers to an animal. The individual may have or be suspected of having an illness or disease. An individual can be a mammal. Non-limiting examples of mammals include humans and animals, such as mice, monkeys, dogs and cats, including transgenic and non-transgenic mice. The methods described herein can be useful in both human, pre-scientific, and veterinary applications. The individual may be a mammal. The individual can be human. Other mammals include, but are not limited to, monkeys, chimpanzees, orangutans, monkeys; domesticated animals (pets), such as dogs, cats, guinea pigs, hamsters, mice, rats, rabbits, and ferrets; domesticated farm animals such as cows, buffalo, bison, horses, donkey, pig, sheep, and goats; or exotic animals typically found in zoos, such as bears, lions, tigers, panthers, elephants, hippopotamus, rhinoceros, giraffes, antelopes, sloth, gazelles, zebras, wildebeest, prairie dogs, koalas, kangaroos, pandas, giant pandas, hyena , seals, sea lions, and elephant seals.
[0023] The term “administer”, as used herein, generally refers to
Petition 870190097797, of 9/30/2019, p. 17/284
10/68 refers to a provision of a composition to an individual, via an administration route, including, but not limited to, intravenous, intra-arterial, oral, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous routes, intraosseous, transmucosal, or intraperitoneal administration. A composition can be administered via a suppository, such as a vaginal or anal suppository. Oral administration routes can be used. A unit dose can be administered via inhalation.
[0024] The term "effective amount or" therapeutically effective amount ", as used herein, generally refers to an amount of a compound described herein that is sufficient to affect a predicted, predetermined, or prescribed application, including, but not limited to, limited to, treatment of disease or condition. The therapeutically effective amount may vary depending on the application (for example, in vitro or in vivo), or the individual and disease condition being treated, for example, the individual's weight and age, the severity of the disease condition and the manner of treatment. administration. The term can also apply to a dose that induces a particular response in target cells, for example, reduced proliferation or downward regulation of activity of a target protein. The specific dose may vary depending on the particular compounds chosen, the dosage regimen to be followed, whether it is administered in combination with other compounds, regulation of administration, the tissue to which it is administered, and the physical delivery system in which it is administered. transported.
[0025] The term "isolated", as used herein, generally refers to a preparation of a substance devoid of at least some of the other components that may also be present where the substance or a similar substance occurs naturally, or is initially obtained from . In this way, for example, an isolated substance can be prepared using a purification technique for
Petition 870190097797, of 9/30/2019, p. 18/284
11/68 to enrich it with a source mixture. Enrichment can be measured on an absolute basis, such as weight per volume of solution, or it can be measured against a second substance that potentially interferes with the source mixture. Increased enrichment can be used. A substance can also be provided in an isolated state by an artificial assembly process, such as chemical synthesis.
[0026] The term "substantially free", as used herein, generally refers to a composition that is less than about 25% (for example, by weight), less than about 15%, less than about 10%, less than about 5%, less than about 1%, less than about 0.5%, less than 0.1%, or even less than a specified component. Such a composition may not have a detectable amount of such a specified component. For example, a composition that is substantially free of a weak acid (for example, an acid with a pKa of at most about 10), may have less than about 1% of the weak acid. The percentage can be determined as a percentage of the total composition, or a percentage of a subset of the composition. For example, a composition that is substantially free of a weak acid may have less than 1% of the weak acid as a percentage of the total composition, or as a percentage of the acids in the composition. The percentages can be percentages of mass, molar, or percentages by volume. The presence or concentration of such a component can be determined spectroscopically, such as chromatography or nuclear magnetic resonance.
[0027] The term "synergistic", as used herein, generally refers to an effect such that the one or more effects of the combination of compositions is greater than one or more effects of each component alone, or they may be greater than that adds them to one or more
Petition 870190097797, of 9/30/2019, p. 19/284
12/68 effects of each component alone. The synergistic effect can be greater than about 10%, 20%, 30%, 50%, 75%, 100%, 110%, 120%, 150%, 200%, 250%, 350%, or 500% or more than the effect on an individual with one of the components alone, or the additive effects of each of the components when administered individually. The effect can be any of the measured effects described here.
[0028] The term "cannabis plant", as used here, generally refers to a plant that is part of a genus of a flowering plant in the Cannabaceae family, and can include three species or subspecies: satlva, indica, and ruderalis . A cannabis plant can comprise a number of different parts, including a node, a plant stem, a leaf, and a flower. The flower of a cannabis plant can be a male flower or a female flower. The female flower may comprise a flower, a pistil, a glue, a trichome, and a chalice.
[0029] The term "cannabinoid", as used here, generally refers to a cannabinoid compound that has been isolated or identified in a cannabis plant. A cannabinoid compound can act on a cannabinoid receptor in a cell. Cannabinoids can alter physiological processes, including altered neurotransmitter release in the brain, appetite, pain, mood, and memory. A cannabinoid compound can have a terpenophenolic C21 nucleus.
[0030] The term "carboxylated cannabinoid", as used here, generally refers to a compound that has been isolated or identified in a cannabis plant, and has a fraction of carboxylic acid (ie, -COOH). A carboxylated cannabinoid can be tetrahydrocannabinolic acid.
[0031] The term "decarboxylated cannabinoid", as used herein, generally refers to a cannabinoid compound that previously has a fraction of carboxylic acid (for example, a
Petition 870190097797, of 9/30/2019, p. 20/284
13/68 carboxylated cannabinoid), and withstands a chemical reaction so as to no longer have the carboxylic acid fraction. A decarboxylated cannabinoid can be a natural compound, and can be present in a cannabis plant. A decarboxy cannabinoid can be synthesized or produced via synthetic methods. A decarboxy cannabinoid can be Δ ⁹ tetrahydrocannabinol.
[0032] The term "terpenoid", as used here, generally refers to an organic compound that is made up of isoprene units, in which each isoprene unit has the formula CsHs. The isoprene units can be connected via covalent bonds. Terpenoids can have the formula (CsHsK in which n is an integer of 1 or more, such as 2, 3, 4, 5, or more. A terpenoid can be a monoterpenoid (Cio support), sesquiterpenoid (C15 support), diterpenoid (support C20), or treterpenoid (support C30) Terpenoids can have beneficial effects on an individual, and can be used as a dietary supplement, or nutritional supplement.
[0033] The term "terpenoid degradation product" as used herein, generally refers to an organic compound that is a product of a reaction carried out on a terpenoid. A terpenoid can degrade into multiple fragments, in which each fragment can be considered as a terpenoid degradation product. A terpenoid degradation product can be carried out during a reaction such as heating, burning, or smoking a terpenoid compound or a composition comprising a terpenoid. A terpenoid degradation product can be formed by applying heat of at least about 50 ° C, 75 ° C, 100 ° C, 200 ° C, 300 ° C, 400 ° C, 500 ° C, 600 ° C, 700 ° C, 800 ° C, 900 ° C, 1000 ° C, or more. A terpenoid degradation product may not have the beneficial properties of the terpenoid from which it was derived.
[0034] Cannabinoid compounds can be divided into ten
Petition 870190097797, of 9/30/2019, p. 21/284
14/68 subclasses. Subclasses of cannabinoid compounds include the canablgerol class, cannabichrome class, cannabidiol class, delta9-tetrahydrocannabinol class, delta-8-tetrahydrocannabinol class, cannabicycline class, cannabinoid and cannabinodiol class, cannabiniol class, and a cannabinoid class.
[0035] Non-limiting examples of cannabinoid compounds in the cannabigerol class include cannabigerolic acid (CBGA), cannabigerolic monomethyl ether (CBGAM), cannabigerol (CBG), cannabigerol monomethyl ether (CBGIVI), cannabigerovarinic acid (CBGVA), and cannabigerovarin (CB) .
[0036] Non-limiting examples of cannabinoid compounds in the cannabichromene class include cannabichromenic acid (CBGA), cannabichromene (CBC), cannabicromevanic acid (CBCVA), and cannabicromevarin (CBCV).
[0037] Non-limiting examples of cannabinoid compounds in the cannabidiol class include cannabidiolic acid (CBDA), cannabidiol (CBD), cannabidiol monomethylether (CBDM), cannabidiol-C4 (CBD-CO, cannabidivarinic acid (CBDVA), cannabidivarin (CBDV) , and cannabidiorcol (CBD-Ci).
[0038] Non-limiting examples of cannabinoid compounds in the lay-9-tetrahydrocannabinol class include delta-9-tetrahydrocannabinolic acid A (THCA-A), delta-9-tetrahydrocannabinolic acid B (THCAB), delta ~ 9 ~ tetrahydrocannabinol (THC ), delta-9-tetrahydrocannabinolic acid-C4 (THCA-C4), delta-9-tetrahydrocannabinoi-C4 (THC-C4), dena-9 tetrahydrocannabivarinic acid (THCVA), delta-9tetrahodrocannabivarin acid (THCV), delta-9 (THCA-C1), delta-9-tetrahydrocannabiorcol (THC-C1), and lie-7-c / s-isotetrahydrocannabivarin.
[0039] Non-limiting examples of cannabinoid compounds in the delta-8-tetrahydrocannabinol class include delta-8-tetrahydrocaine
Petition 870190097797, of 9/30/2019, p. 22/284
15/68 nabinolic (Á ⁸ -THCA), and delta-8-tetrahydrocannabinol (Á ⁸ -THC).
[0040] Non-limiting examples of cannabinoid compounds in the cannabicyclol class include cannabicyclolic acid (CBLA), cannabicyclol (CBL), and cannabicyclovarin (CBLV).
[0041] Non-limiting examples of cannabinoid compounds in the cannabielsoin class include cannabielsómico acid A (CBEA-A), cannabielsóico acid B (CBEA-B), and cannabielsoina (CBE).
[0042] Non-limiting examples of cannabinoid compounds in the cannabinol and cannabinodiol class include cannabinolic acid (CBNA), cannabinol (CBN), cannabinol methylether (CBNM), cannabinol-C4 (CBN-C4), cannabinol (CBV), cannabinol- Cs (CBN-C2), cannabiorcol (CBN-Ci), cannabinodiol (CBND), and cannabinodivarin (CBVD).
[0043] Non-limiting examples of cannabinoid compound in the cannabitriol class include cannabitriol (CBT), 10-ethoxy-9-hydroxy-delta6a-tetrahydrocannabinol, 8,9-dihydroxy-delta-6a-tetrahydrocannabinol, cannabitriolvarin (CBTV), and ethoxy-cannabitriolvarin (CBTVE).
[0044] Non-limiting examples of cannabinoid compounds in the miscellaneous cannabinoid class include dehydrocannabifuran (DCBF), cannabifuran (CBF), cannabicromanon (CBCN), cannabicitran (CBT), 10-oxo ~ delta ~ 6a-tetrahydrocannabinol) , delta-9-c / s ~ tetrahydrocannabinol (cis-THC), 3,4,5,6-tetrahydro-7-hydroxy-a / fa-a / fa-2trimethi1-9-n-propyl-2,6- methane-2H-1-benzoxocin-5-methanol (OH-isoHHCV), cannabiripsol (CBR), and trihydroxy-delta-9-tetrahydrocannabinol (triOH-THC).
[0045] Terpenoid compounds that have been isolated from the essential oil of a cannabis plant may include myrcene, limonene, linalool, trans-ocimene, befa-pinene, a / fa-pinene, befa-cariodylene, delta-3-carene , trans-gamma-bisabolene, trans-a / fa-farnesene, betafenchol, beta-felandrene, a / fa ~ humulene (a / fa ~ karyophylene), guajol, alphanuanian, a / fa-eudesmol, terpinolene, a / fa- selinene, a / fa-terpineol, fen
Petition 870190097797, of 9/30/2019, p. 23/284
16/68 chone, camphene, w / s-sabinene hydrate, w / s-ocimene, deta-eudesmol, befa-selinene, a / fa-frans-bergamotene, gamma-eudesmol, borneol, cisdeta-famesene, gamma-curcumene, c / s-gamma ~ bisabolene, a / fa-thujeno, epi-a / fa-bisabolol, ipsdienol, a / fa-ilangene, befa-eiemene, alpha-cisbergamotene, gamma-muurolene, a / fa-cadinene, a / fa-longipinene, and karyophylene oxide.
[0046] Compounds containing nitrogen were isolated from a cannabis plant. Escanidine top alkaloids that have been isolated from cannabis sativa may include cannabisativin and anhydrocannabisativin. Other nitrogen-containing compounds that have been isolated from a cannabis plant include, but are not limited to, n-transferulohitiramine, np-coumaroiltiramine, n-trans-caffeylthyramine, grossamide, cannabisin-A, cannabisin-B, cannabisin-C, and cannabisine -D.
[0047] Flavonoids are compounds that can be secondary metabolites of plants or fungi. Generally, flavonoids have a Cis support. Flavonoids were identified in a cannabis plant, including apigenin, luteolin, kaempferol, quercetin, orientin, vitexin, canflavine A, and canflavin B.
[0048] Additional compounds that have been isolated from a cannabis plant include unsaturated fatty acids and non-cannabinoid phenols, including, but not limited to, linoleic acid, a / fa-linolenic acid, oleic acid, cannabispirane, isocannabispirane, cannabistylbene-l , cannabistylbeno-ll, canitreno-1, and canitreno-2.
Compositions [0049] The present disclosure provides a unit dose of a composition that can comprise a mixture of carboxylated cannabinoids and decarboxylated cannabinoids, and one or more terpenoids. The composition may comprise decarboxylated cannabinoids (e.g., Δ ⁹ tetrahydrocannabinol) and carboxylated cannabinoids (e.g., tetrahydrocannabinolic acid).
Petition 870190097797, of 9/30/2019, p. 24/284
17/68 [0050] The composition may comprise a ratio of decarboxylated cannabinoids to carboxylated cannabinoids of at least about 0.01: 1, 0.05: 1, 0.1: 1, 0.5: 1, 1: 1 , 2: 1, 3: 1, 4: 1.5: 1, 6: 1, 7: 1, 8: 1, 9: 1, 10: 1, 20: 1, 30: 1, 40: 1, 50 : 1, 60: 1, 70: 1, 80: 1, 90: 1, 100: 1, or more. The ratio of decarboxylated cannabinoids to carboxylated cannabinoids can also be described as a single value of at least about 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7 , 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, or more. The ratio of decarboxylated cannabinoids to carboxylated cannabinoids in a composition of the present disclosure, or a unit dose may be different than the proportion of products isolated directly from a natural source. For example, a ratio of decarboxylated cannabinoids (eg, Δ ⁹ tetrahydrocannabinol) to carboxylated cannabinoids (eg, tetrahydrocannabinolic acid) can be 0.05: 1 when isolated from a natural source, such as a cannabis plant. After supporting a method described here, the ratio of decarboxylated cannabinoids (for example, Δ ⁹ tetrahydrocannabinol) to carboxylated cannabinoids (for example, tetrahydrocannabinolic acid), can be 1: 1, 2: 1.5: 1, or higher.
[0051] Any of the components described herein, including Δ ⁹ tetrahydrocannabinol, can be used in a composition in free form, isolated form, purified from a natural source, and / or purified or prepared from a synthetic source. The natural source can be an animal source or a plant source. The components can be pure to at least about 95, 97, 99, 99.5, 99.9, 99.99, or 99.999%.
[0052] A dose of the present disclosure, which may be a unit dose, may comprise more than about 1 milligram (mg), 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg , 80 mg, 90 mg, or 100 mg of a compound
Petition 870190097797, of 9/30/2019, p. 25/284
18/68 cannabinoid. A dose of a composition of the present disclosure, which may be a unit dose, can comprise about 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg , or 100 mg of a cannabinoid compound. A dose of a composition of the present disclosure, which may be a unit dose, may comprise less than about 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg , 90 mg, or
100 mg of a cannabinoid compound.
[0053] A unit dose of Δ ⁹ tetrahydrocannabinol can be at least about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, or 1000 mg . A unit dose of Δ ⁹ tetrahydrocannabinol can be from about 1 mg to about 20 mg, from 3 mg to about 15, from 5 mg to about 10 mg. A dose of Δ ⁹ tetrahydrocannabinol can comprise at least about 0.001 moles (mol) of Δ ⁹ tetrahydrocannabinol, 0.005 mol !, 0.01 mol, 0.015 mol, 0.02 mol, 0.03 mol, 0.04 mol, 0 , 05 mol, 0.06 mol, 0.07 mol, 0.08 mol, 0.09 mol, 0.1 mol, 0.2 mol, 0.3 mol, 0.4 mol, 0.5 mol, or more.
[0054] A unit dose can comprise at least about 10 milligrams (mg), 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg , 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, or 1000 mg of tetrahydrocannabinolic acid.
[0055] A unit dose can comprise at least about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg,
Petition 870190097797, of 9/30/2019, p. 26/284
19/68
100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg , 950 mg, or 1000 mg of a terpenoid.
[0056] A unit dose can be substantially free of a terpenoid degrading compound. A unit dose can comprise less than about 1000 mg, 900 mg, 800 mg, 700 mg, 600 mg, 500 mg, 400 mg, 300 mg, 200 mg, 100 mg, 50 mg, 40 mg, 30 mg, 20 mg, or 10 mg of a terpenoid degrading compound. A unit dose can comprise less than about 1000 mg, 900 mg, 800 mg, 700 mg, 600 mg, 500 mg, 400 mg, 300 mg, 200 mg, 100 mg, 50 mg, 40 mg, 30 mg, 20 mg, or 10 mg of multiple terpenoid degrading compounds. A unit dose can comprise less than about 10%, 5%, 4%, 3%, 2%, 1%, 0.1%, or 0.01% of a terpenoid degrading compound by weight. A unit dose can comprise less than about 10%, 5%, 4%, 3%, 2%, 1%, 0.1%, or 0.01% of a terpenoid degrading compound by volume. A unit dose can comprise at most about 1000 mg, 900 mg, 800 mg, 700 mg, 600 mg, 500 mg, 400 mg, 300 mg, 200 mg, 100 mg, 50 mg, 40 mg, 30 mg, 20 mg , or 10 mg of a terpenoid degrading compound.
[0057] A unit dose can be substantially free of an acid, in which the acid can be used to convert a carboxylated cannabinoid to a decarboxylated cannabinoid. A unit dose can comprise less than about 1000 mg, 900 mg, 800 mg, 700 mg, 600 mg, 500 mg, 400 mg, 300 mg, 200 mg, 100 mg, 50 mg, 40 mg, 30 mg, 20 mg, or 10 mg of an acid. A unit dose can comprise less than about 1000 mg, 900 mg, 800 mg, 700 mg, 600 mg, 500 mg, 400 mg, 300 mg, 200 mg, 100 mg, 50 mg, 40 mg, 30 mg, 20 mg, or 10 mg of multiple acids. A unit dose can comprise less than about 10%, 5%, 4%, 3%, 2%,
Petition 870190097797, of 9/30/2019, p. 27/284
20/68
1%, 0.1%, or 0.01% of an acid by weight. A unit dose can comprise less than about 10%, 5%, 4%, 3%, 2%, 1%, 0.1%, or 0.01% of an acid by volume. A unit dose can comprise at most about 1000 mg, 900 mg, 800 mg, 700 mg, 600 mg, 500 mg, 400 mg, 300 mg, 200 mg, 100 mg, 50 mg, 40 mg, 30 mg, 20 mg , or 10 mg of an acid.
[0058] A unit dose of a composition of the present disclosure may result in a blood concentration, blood plasma concentration, or blood content of a compound in the composition in a certain amount after a given period of time. A unit dose of a composition can result in a blood content that can be measured from a blood sample, a blood plasma sample, a urine sample, a saliva sample, the individual's breath, or other fluid samples corporeal.
[0059] A unit dose of a cannabinoid can result in a blood concentration of the cannabinoid of at least about 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5 , 3, 4, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 300, 400 , 500 nanograms per milliliter (ng / mL), or greater. Alternatively, the cannabinoid unit dose may result in a cannabinoid blood concentration of at most about 500, 400, 300, 200, 190, 180, 170, 160, 150, 140, 130, 120, 110, 100, 90 , 80, 70, 60, 50, 40, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0.5 ng / ml. A single dose of a cannabinoid can result in a cannabinoid blood concentration of about at least about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 ng / mL or higher. A unit dose of a cannabinoid can result in a cannabinoid blood concentration of 10 to 200 ng / mL, 50 to 190 ng / mL, or 90 to 170 ng / mL.
[0060] A daily dose of a cannabinoid can result in a blood concentration of the cannabinoid of at least about 0.5
Petition 870190097797, of 9/30/2019, p. 28/284
21/68 ng / mL, 0.75 ng / mL, 1 ng / mL, 1.25 ng / mL, 1.5 ng / mL, 1.75 ng / mL, 2 ng / mL, 2.5 ng / mL, 3 ng / mL, 4 ng / mL, 5 ng / mL, 10 ng / mL, 20 ng / mL, 30 ng / mL, 40 ng / mL, 50 ng / mL, 60 ng / mL, 70 ng / mL, 80 ng / mL, 90 ng / mL, 100 ng / mL, 110 ng / mL, 120 ng / mL, 130 ng / mL, 140 ng / mL, 150 ng / mL, 160 ng / mL, 170 ng / ml, 180 ng / ml, 190 ng / ml, 200 ng / ml, 300 ng / ml, 400 ng / ml, 500 ng / ml, or higher. A unit dose of a cannabinoid can result in a cannabinoid blood concentration of 10 to 200 ng / mL, 50 to 190 ng / mL, or 90 to 170 ng / mL.
[0061] Blood levels of a cannabinoid can peak at about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, or 20 minutes after the first dose of a cannabinoid. Blood levels of a cannabinoid can remain detectable for about 1 minute, 2 minutes, 5 minutes, 10 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 18 hours , 24 hours, or 36 hours after the last dose of cannabinoid.
[0062] A composition of the present disclosure can be used in combination therapy. A combination therapy can be administered by a combination treatment regimen. A combination treatment regimen may involve treatment regimens in which administration of a compound described herein, or a pharmaceutically acceptable salt thereof, is initiated before, during, or after treatment with a second agent, and may continue until any time during treatment with the second agent, or after termination of treatment with the second agent. The second agent being used in combination can be administered simultaneously or at different times and / or at reduced or increased intervals during the treatment period than the first agent.
[0063] A composition of the present disclosure can comprise two or more compounds. A composition can comprise two or more compounds of the present disclosure.
Petition 870190097797, of 9/30/2019, p. 29/284
22/68 [0064] A composition of the present disclosure can be used in conjunction with an opioid. The opioid can act on an opioid receptor administration to an individual. The combination of a composition of the present disclosure and an opioid can have a synergistic effect on an individual. Combination therapy can grant little and less the severity of side effects seen compared to when a compound or composition is administered as a single agent.
[0065] A composition of the present disclosure can be used in conjunction with a chemotherapy agent (e.g., paclitaxel, docetaxel, doxorubicin, bortezomib, gemcltabine, or cisplatin), or chemotherapy treatment. The chemotherapy agent or treatment can be radiation, hormonal therapy, targeted therapy, or a cytotoxic agent. When used in conjunction with chemotherapy treatment, the composition and treatment of chemotherapy may exhibit synergistic effects.
[0066] A combination composition can be formulated to achieve a given, desired or predetermined molar ratio or mass ratio between two or more compounds in the composition. The molar ratio can be adjusted to account for the bioavailability, input, and metabolic processing of one or more components of a combination composition. For example, if the bioavailability of a component is low, then the molar amount of that component can be increased relative to other components in the combination composition. The molar or circulating mass ratio can be reached within about 0.1, 0.5, 0.75, 1, 3, 5, or 10, 12, 24, or 48 hours after administration. The molar or circulating mass ratio can be maintained for a period of time of about or greater than about 0.1, 1, 2, 5, 10, 12, 18, 24, 36, 48, 72, or 96 hours.
Petition 870190097797, of 9/30/2019, p. 30/284
23/68
Dosage forms [0067] The compositions described herein can be composed in a variety of different dosage forms. They can be in the form of oral dosage. The composition can be used orally, such as, for example, in the form of a tablet, a capsule, a pill, a granule, an emulsion, a gel, a plurality of spheres encapsulated in a capsule, a powder, a suspension, a liquid, a semi-liquid, a semi-solid, a syrup, a slurry, a chewable form, soft gelatin capsules, pills or solution. Alternatively, a composition can be formulated for inhalation or for intravenous delivery. The compositions can also be formulated as a nasal spray, or for injection when in the form of a solution. Alternatively, the composition may be a liquid composition suitable for oral consumption.
[0068] A composition can also be formulated on a solid or semi-solid support. The composition can be formulated in or in a polymeric material (for example, silicone), and can be used as an injectable polymeric material (for example, silicone) to prevent blood loss during traumatic injury or surgery. The polymeric material can be a biopolymer. The biopolymer can be biodegradable or absorbable in the individual for a period of time.
[0069] Polymeric material can facilitate wound repair, assist in a decrease in pain perceived by the individual, exhibit antimicrobial properties, such as slowing the growth of microorganisms, or facilitate homeostatic balance in or around the wound in the individual as a whole . The polymeric material can decrease shock, trauma, or oxidative stress to the area of or around the wound, or on the individual. The polymeric material can also be used as a vehicle for delivering therapeutic material. In some cases, a composition of the present disclosure and a second material
Petition 870190097797, of 9/30/2019, p. 31/284
Therapeutic 24/68 can be formulated in a polymeric material that is used before, during, or after a surgical procedure or trauma.
[0070] The composition can be formulated for use during and after a surgical procedure, such as in a medical device. The medical device can be a suture, a plunger, wire, an implant, or a prosthesis. The composition can be formulated in a material that is biodegradable or absorbable, and can degrade inside the body after at least about 1 day, 2 days, 3 days, 7 days, 1 month, 2 months, or more. Alternatively, the medical device (e.g., suture or plunger) may be non-biodegradable or non-absorbable. The composition can facilitate a slow release of compounds from the composition, which may be desired. The compositions can be formulated in a medical device that is implanted in an individual during surgery, and can release one or more components over a period of 1.4, 6, 8, 12, 16, 20, 24, 36, 48 , or more hours.
[0071] A composition described here can be used to enhance the success or results of an implant or prophetic procedure. For example, a composition can be administered before, during, or after an implant procedure. Implants can be used to replace a missing biological structure, damaged structure support, or to enhance existing structure. In some embodiments, an implant can be subdermal. In some embodiments, an implant can be transdermal. Implants may include, for example, cardiovascular implants, orthopedic implants, contraception implants, cosmetic implants, prophetic limbs, and eye implants. In some cases, an implant can be a neural loop, and it can be implanted in the cavity of the head, and it can be in or near the brain. In some cases, a composition described herein can provide benefits for neuroplasticity, and can positively alter the brain's ability to change over time. At
Petition 870190097797, of 9/30/2019, p. 32/284
25/68 compositions formulated for inhalation can be packaged in an inhaler or nebulizer. An inhaler can be designed to deliver 0.25, 0.5, or 1 unit dose per inhalation. An inhaler may have a container that holds the object composition formulated for inhalation, a metering valve that allows a measured amount of the formulation to be dispensed with each actuation, and an actuator or nozzle that allows the device to be operated and direct the object composition in the lungs of the individual. The formulated composition can include a liquefied gas propellant and possibly stabilizing excipients. The actuator may have a discharge nozzle that connects to the container and a dust cover to prevent contamination of the actuator. After performance, the object composition can be volatilized, which results in the formation of droplets of the object composition. The droplets can quickly evaporate resulting in micrometer sized particles that can then be inhaled by the individual. [0072] The compositions of the present disclosure suitable for oral administration can be presented as discrete dosage forms, such as capsules, or tablets, or aerosol sprays or liquids each containing a predetermined amount of an active ingredient as a powder or granules , a solution, or a suspension in an aqueous or non-aqueous liquid, an oil-in-water emulsion, or a water-in-oil liquid emulsion, including liquid dosage forms (for example, a suspension or slurry), and forms solid oral dosing systems (for example, a pill or bulk powder). Oral dosage forms can be formulated as tablets, pills, pills, capsules, emulsions, lipophilic and hydrophilic suspensions, liquids, gels, syrups, slurries, suspensions, for oral ingestion by an individual, patient, or individual to be treated. Such dosage forms can be prepared by any of the formulation methods. For example, active ingredients can
Petition 870190097797, of 9/30/2019, p. 33/284
26/68 must be brought in association with a carrier, which constitutes one or more necessary ingredients. Capsules suitable for oral administration include push-fit capsules made of gelatin, as well as soft sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. Push-fit capsules can contain the active ingredients in the charged mixture, such as lactose, binders such as starches, and / or lubricants such as taico or magnesium stearate and, in some cases, stabilizers. The composition for oral use can be obtained by mixing a composition comprising a solid excipient, in some cases, grinding a resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or pill cores. . Excipients can be fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth, methyl cellulose, hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose, and / or polyvinylpyrolidone (PVP). The compositions that are prepared can be prepared by uniformly and intimately mixing the active ingredient with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into the desired presentation. For example, a tablet can be prepared by compression or molding, in some cases, with one or more accessory ingredients. Compressed tablets can be prepared by compression in a suitable machine of the active ingredient in a free-flowing form, such as powder or granules, in some cases, mixed with an excipient such as, but not limited to, a binder, a lubricant, an inert diluent, and / or a surface active or dispersing agent. Molded tablets can be produced by molding in a suitable machine a mixture of the compound
Petition 870190097797, of 9/30/2019, p. 34/284
27/68 powder moistened with an inert liquid thinner.
[0073] Liquid forms, in which the formulations disclosed herein may be incorporated for administration orally or by injection, include aqueous solution, suitably flavored syrups, aqueous or oil suspensions, and emulsions flavored with edible oils such as cottonseed oil , sesame oil, coconut oil, or peanut oil, as well as elixirs and similar pharmaceutical vehicles. Suitable dispersing or suspending agents for aqueous suspensions include synthetic natural gums, such as tragacanth, acacia, alginate, dextran, sodium carboxymethyl cellulose, methylcellulose, polyvinylpyrrolidone or gelatin.
[0074] Liquid preparations for oral administration can take the form of, for example, solutions, syrups or suspensions, or they can be presented as a dry product for reconstitution with water or other suitable vehicles before use. Such liquid preparations can be prepared by conventional approaches with pharmaceutically acceptable additives, such as suspending agents (for example, sorbitol syrup, methyl cellulose or hydrogenated edible fats); emulsifying agents (for example, lecithin or acacia); non-aqueous vehicles (for example, almond oil, oily esters or ethyl alcohol); preservatives (for example, methyl or propyl p-hydroxybenzoates or sorbic acid); and artificial or natural colors and / or sweeteners.
[0075] This disclosure further involves anhydrous compositions and dosage forms comprising an active ingredient, since water can facilitate the degradation of some compounds. For example, water can be added (for example, 5%) to encourage long-term storage in order to determine characteristics such as half-life or the stability of formulations over time. Anhydrous compositions and dosage forms of the present disclosure
Petition 870190097797, of 9/30/2019, p. 35/284
28/68 can be prepared using anhydrous or low humidity ingredients and low unit conditions. The compositions and dosage forms of the present disclosure that contain lactose can be made anhydrous if substantial contact with hydration and / or moisture during manufacture, packaging, and / or storage is expected. An anhydrous composition can be prepared and stored such that its anhydrous nature is maintained. Consequently, anhydrous compositions can be smudged using materials that prevent exposure to water so that they can be included in suitable form kits. Examples of suitable packaging include, but are not limited to, hermetically sealed sheets, plastic, unit dose containers, bubble wrap packaging, and strip packaging.
[0076] An ingredient described herein can be combined in an intimate mixture with a pharmaceutical carrier according to conventional pharmaceutical composition techniques. The carrier can take a variety of forms depending on the form of preparation desired for administration. In the preparation of compositions for an oral dosage form, pharmaceutical medium can be employed as carriers, such as, for example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents, in the case of oral liquid preparations ( such as suspensions, solutions, and elixirs) or aerosols; or carriers such as starches, sugars, micro crystalline cellulose, diluents, granulating agents, lubricants, binders, and disintegrating agents, can be used in the case of solid oral preparations, with or without the use of lactose. For example, suitable carriers include powders, capsules, and tablets, with solid oral preparations. If desired, the tablets can be coated by standard aqueous or non-aqueous techniques.
[0077] Some examples of materials that can serve as
Petition 870190097797, of 9/30/2019, p. 36/284
29/68 pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, corn oil, and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other compatible non-toxic substances used in pharmaceutical formulations.
[0078] Binders suitable for use in dosage forms include, but are not limited to, corn starch, potato starch, or other starches, gelatin, natural and synthetic gums such as acacia, sodium alginate, alginic acid, other alginates , powdered tragacanth, guar gum, cellulose and its derivatives (for example, ethyl cellulose, cellulose acetate, carboxymethyl cellulose calcium, sodium carboxymethyl cellulose), polyvinyl plrrolidone, methyl cellulose, pregelatinized starch, hydroxypropyl methyl cellulose, microcrystalline cellulose, and mixtures of these.
[0079] Lubricants that can be used to form compositions and dosage forms of the present disclosure include, but are not limited to, calcium stearate, magnesium stearate, mineral oil, light mineral oil, glycerin, sorbitol, mannitol, polyethylene glycol, other glycols, stearic acid, sodium lauryl sulfate, talc, hydrogenated vegetable oil (eg, peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, mi oil
Petition 870190097797, of 9/30/2019, p. 37/284
30/68
Iho, and soy oil), zinc stearate, ethyl oleate, ethyl ethyleate, agar, or mixtures thereof. Additional lubricants include, for example, a silico silica gel, a coagulated synthetic silica aerosol, or mixtures thereof. A lubricant can be added, such as, for example, in an amount of less than about 1 percent by weight of the composition.
[0080] Lubricants can also be used in conjunction with fabric barriers that include, but are not limited to, polysaccharides, polyglycans, seprafilm, interceed and hyaluronic acid.
[0081] Disintegrants can be used in the compositions of the present disclosure to provide tablets that disintegrate when exposed to an aqueous environment. Much more than one disintegrant can produce pills that can disintegrate in the bottle. Very little can be insufficient for disintegration to occur and can thus alter the rate and extent of release of the active ingredient (s) from the dosage form. Thus, a sufficient amount of disintegrant that is neither too little nor too much to adversely alter the release of the active ingredient (s) can be used to form the dosage forms of the compounds disclosed herein. The amount of disintegrant used can vary based on the type of formulation and mode of administration, and can be readily discernible to that person skilled in the art. About 0.5 to about 15 percent by weight of disintegrant, or about 1 to about 5 percent by weight of disintegrant, can be used in the pharmaceutical composition. Disintegrants that can be used to form compositions and dosage forms of the present disclosure include, but are not limited to, agar-agar, alginic acid, calcium carbonate, micro crystalline cellulose, croscarmellose sodium, crospovidone, potassium polacrilin, sodium glycolate starch , potato or tapioca starch, other starches, pregelatinized starch, other starches, clays,
Petition 870190097797, of 9/30/2019, p. 38/284
31/68 other algins, other celluloses, gums, or mixtures thereof.
[0082] Examples of fillers suitable for use in the compositions and dosage forms disclosed herein include, but are not limited to, talc, calcium carbonate (e.g., granules or powder), micro crystalline cellulose, powdered cellulose, dextrates, kaolin , mannitol, silicic acid, sorbitol, starch, pregelatinized starch, and mixtures thereof.
[0083] In some cases, aqueous suspensions and / or elixirs may be desired for oral administration. In such cases, the active ingredient can be combined with various sweetening or flavoring agents, coloring matter or dyes and, if desired, emulsifying and / or suspending agents, together with diluents such as water, ethanol, propylene glycol, glycerin, or various combinations of these. [0084] The tablets can be uncoated or coated to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action for a longer period. For example, a time-delaying material, such as glyceryl monostearate or glyceryl distearate, can be employed. Formulations for oral use can also be presented as hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate, or kaolin, or as soft gelatin capsules in which the ingredient active is mixed with water or an oil medium, for example, peanut oil, liquid paraffin, or olive oil.
[0085] In one embodiment, the composition may include a solubilizer to ensure good solubilization and / or dissolution of the compound of the present disclosure, and to minimize precipitation of the compound of the present disclosure. This can be especially important for compositions for non-oral use, for example, compositions for injection. A solubilizer can also be added to increase the solubility of the hydrophilic drug and / or other components, such as
Petition 870190097797, of 9/30/2019, p. 39/284
32/68 surfactants, or to maintain the composition as a stable or homogeneous solution or dispersion.
[0086] The composition may additionally include one or more pharmaceutically acceptable additives or pharmaceutically acceptable excipients. Such additives and excipients include, without limitation, anti-foaming agents, anti-foaming agents, buffering agents, polymers, antioxidants, preservatives, chelating agents, viscomodulators, toners, flavorings, dyes, odorants, opacifiers, suspending agents, binders, fillers, plasticizers, lubricants, and mixtures thereof. A non-exhaustive list of examples of excipients includes monoglycerides, magnesium stearate, modified food starch, gelatin, microcrystalline cellulose, glycerin, stearic acid, silica, yellow beeswax, lecithin, hydroxypropylcellulose, croscarmellose sodium, and crospovidone.
[0087] In some embodiments, a compound or composition described herein can be formulated or administered in combination with another active ingredient or ingredients. In some cases, a cannabinoid composition can be administered with psychedelic compounds for therapeutic intensification. Therapeutic intensification can be via optimization of the endocannabinoid system, neuroplasticity, neural decrease, anti-psychotic effects, anxiety effects, intensified neurogenesis, or a combination of these.
[0088] In some cases, a cannabinoid composition as described herein can be used in combination with psychedelic compounds, such as 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, lysergic acid diethylamide (LSD). In some cases, a cannabinoid composition can be used in combination with psychedelic aided therapeutic programs, and can aid in overall effectiveness.
[0089] The compositions described here can also be formulated
Petition 870190097797, of 9/30/2019, p. 40/284
33/68 as extended release, slow release, sustained release, or release over time, such that one or more components are released over time. The compositions of the present disclosure can have half-lives of at least about 1 minute, 10 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 1 day, 2 days , 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, or more. Delayed release can be achieved by formulating one or more components in a matrix of a variety of materials or by micro encapsulation (for example, micro encapsulation in a material that has a predetermined rate of degradation, or a material with pores with pore sizes that allow controllable release). The compositions can be formulated to release one or more components over a period of 1.4, 6, 8, 12, 16, 20, 24, 36, or 48 hours. The release of one or more components can be at a constant rate or rate of change.
[0090] A composition described herein can be formulated as matrix pellets in which particles of the object composition are embedded in a water-insoluble plastic matrix, and which are enclosed by a water-insoluble plastic membrane containing particles soaked in lactose, produces and maintains plasma levels of the subject composition within the target therapeutic range. A composition can be formulated as a sustained or controlled release capsule or tablet. A sustained or controlled release tablet can be formed by coating core granules composed mainly of the object composition with a layer of a coating film composed of a hydrophobic material and a plastic excipient and, in some cases, containing an enteric polymer material , to form coated granules and then by compressing the coated granules together with an excipient of
Petition 870190097797, of 9/30/2019, p. 41/284
34/68 syncration. Such a sustained or controlled release capsule or tablet can release the composition in a substantially sustained or controlled manner over a given period of time, such as a substantially constant rate of release over a period of at least 0.1 hour, 0.5 hour , 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 24 hours, or more. Such a sustained or controlled release capsule or tablet may allow at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or greater of the composition to be be released over a period of time of at least 0.1 hour, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 12 hours, 24 hours, or more.
[0091] Using the controlled release dosage forms provided herein, the one or more cofactors can be released in their dosage form at a slower rate than observed for an immediate formulation release of the same amount of components. The rate of change in the biological sample can be measured as the change in concentration over a defined time period of administration to maximum concentration for a controlled release formulation is less than about 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% of the rate of the immediate release formulation. The rate of change in concentration over time may be less than about 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% of the rate for the immediate release formulation.
[0092] The rate of change of concentration over time can be reduced by increasing the time to maximum concentration in a relatively proportionate manner. For example, a two-fold increase in time to maximum concentration can reduce the rate of change in concentration by approximately a factor of 2. As a result, one or more cofactors can be provided so that it reaches its maximum concentration at a rate that is significant
Petition 870190097797, of 9/30/2019, p. 42/284
35/68 reduced on an immediate release dosage form. The compositions of the present disclosure can be formulated to provide a change in maximum concentration for 24 hours, 16 hours, 8 hours, 4 hours, 2 hours, or at least 1 hour. The associated reduction in the rate of change in concentration can be by a factor of about 0.05, 0.10, 0.25, 0.5 or at least 0.8. This can be accomplished by releasing less than about 30%, 50%, 75%, 90%, or 95% of the one or more cofactors into the circulation within an hour of such administration.
[0093] Controlled release formulations may exhibit plasma concentration curves having initial slopes (for example, from 2 hours after administration to 4 hours after administration) less than 75%, 50%, 40%, 30%, 20% or 10% of those for an immediate release formulation of the same dosage of the same cofactor.
[0094] The rate of release of the cofactor as measured in dissolution studies can be less than about 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% of the rate for a immediate release formulation of the same cofactor over the first 1, 2, 4, 6, 8, 10, or 12 hours.
[0095] The controlled release formulations provided here can take a variety of formats. The formulation can be in an oral dosage form, including liquid dosage forms (for example, a suspension or slurry), and solid oral dosage forms (for example, a tablet or bulk powder), such as, but not limited to those described here.
[0096] Tablets or pills can also be coated or otherwise composed to provide a dosage form that provides the long-acting advantage. For example, the tablet or pill may comprise an internal dosage and external dosage component, the latter being in the form of an envelope
Petition 870190097797, of 9/30/2019, p. 43/284
36/68 on the first. The two components can be separated by an enteric layer that serves to resist disintegration in the stomach, and allows the internal component to pass intact in the duodenum, or to be delayed in release. A variety of materials can be used for such enteric layers or coatings such as materials including a number of polymeric acids and mixtures of polymeric acids with such materials as shellac, cetyl alcohol and cellulose acetate. A formulation comprising a plurality of cofactors can have different cofactors released at different rates or at different times. For example, there may be additional layers of interspersed cofactors with enteric layers.
[0097] The compositions can be formulated into a food composition. For example, the compositions can be a beverage or other liquids, solid food, semi-solid food, with or without a food carrier. For example, the compositions may include a black tea supplemented with any of the compositions described herein. The composition can be a dairy product supplemented with any of the compositions described herein. The compositions can be formulated into a food composition. For example, the compositions can comprise a beverage, solid food, semi-solid food, or a food carrier.
[0098] Liquid food carriers, such as in the form of beverages, such as supplemented juices, coffees, teas, sodas, and flavored waters, can be used. For example, the beverage may comprise the formulation, as well as a liquid component, such as various deodorants or natural carbohydrates present in conventional drinks. Examples of natural carbohydrates include, but are not limited to, monosaccharides, such as, glucose and fructose; disaccharides, such as maltose and sucrose; conventional sugars, such as dextrin and cyclodextrin; and sugar alcohols, such as
Petition 870190097797, of 9/30/2019, p. 44/284
37/68 xylitol and erythritol. Natural deodorants, such as thaumatin, stevia extract, Levaudioside A, glycyrrhizin, and synthetic deodorizer such as saccharin and aspartame, can also be used. Agents such as flavoring agents, coloring agents, and the like, can also be used. For example, pectic acid and its salt, alginic acid, and its salt, organic acid, protective colloidal adhesive, pH control agent, stabilizer, a preservative, glycerin, alcohol, or carbonizing agents, can also be used. Fruits and vegetables can also be used in the preparation of food or drinks comprising the formulations discussed here.
[0099] Alternatively, the compositions can be a snack bar supplemented with any of the compositions described here. For example, the snack bar can be a chocolate bar, a granola bar, or a dry fruit bar. In yet another embodiment, the present dietary supplement or food compositions are formulated to have a suitable and desirable taste, texture, and viscosity for consumption. Any suitable food carrier can be used in the present food compositions. The food carriers of the present disclosure include almost any food product. Examples of such food carriers include, but are not limited to, food bars (granola bars, protein bars, chocolate bars, etc.), cereal products (oats, breakfast cereals, granola, etc.), products bakery products (bread, donuts, cookies, donuts, sweets, cakes, etc.), beverages (milk-based drinks, sports drinks, fruit juices, alcoholic drinks, bottled water), pastes, grains (rice, corn, oats , rye, wheat, flour, etc.), egg products, snacks (sweets, chips, gum, chocolate, etc.), meats, fruits, and vegetables. In one embodiment, the food carriers employed here can mask the undesirable taste (e.g., bitterness). Where
Petition 870190097797, of 9/30/2019, p. 45/284
38/68 desired, the food composition presented here exhibits more desired textures and aromas than those of any of the components described herein. For example, liquid food carriers can be used according to the present disclosure to obtain the present food compositions in the form of drinks, such as supplemented juices, coffees, teas. Solid food carriers can be used in accordance with the present disclosure to obtain the present food compositions in the form of meal replacements, such as supplemented snack bars, pasta, breads. Alternatively, semi-solid food carriers can be used in accordance with the present disclosure to obtain the present food compositions in the form of gums, or chewable candies, or snacks.
Methods [00100] In some embodiments, the present disclosure provides a method of converting a carboxylated cannabinoid to a decarboxylated cannabinoid. Such conversion may include removal of a carboxylic acid group from the carboxylated cannabinoid.
[00101] In some embodiments, the present disclosure provides a method of supplementing a cannabinoid compound and a terpenoid to an individual in need thereof, comprising administering a unit dose of a composition described herein.
[00102] The method of converting a carboxylated cannabinoid to a decarboxylated cannabinoid can be a chemical reaction. The conditions of the chemical reaction may comprise a catalyst, such as an acid, to facilitate the conversion of a carboxylated cannabinoid to a decarboxylated cannabinoid. A used acid can be a weak acid. The acid can have a pKa that is at most about 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0, -1, -2, -3, -4, -5, - 6, -7, -8, -9, -10,
Petition 870190097797, of 9/30/2019, p. 46/284
39/68 or less. The acid can have a pKa that is at least about -10, 9, -8, -7, -6, -5, -4, -3, -2, -1,0, 1,2, 3, 4 , 5, 6, 7, 8, 9, or more. The acid can have a pKa that is about -10 to about 10, about -7 to about 7, about -3 to about 7, about -1 to about 7, about from 3 to about 7, or from about 4 to about 6, or from about 5 to 7. In some embodiments the acid has a pKa of at most about 20, 15, 10, or 5. In some embodiments the acid has a pKa of at least about -10, -5, 0, 5, or more. The acid can be a weak acid. The acid can be a strong acid. The acid can be an organic acid. The acid can comprise a fraction of carboxylic acid. The acid may have a molecular weight of less than about 500 daltons, 400 daltons, 300 daltons, 200 daltons, 100 daltons, 90 daltons, 80 daltons, 70 daltons, 60 daltons, 50 daltons, 40 daltons, or less.
[00103] The amount of acid used to convert a carboxylated cannabinoid (eg, tetrahydrocannabinolic acid) to a decarboxylated cannabinoid (eg, Δ ⁹ tetrahydrocannabinol) can be selected such that the acid is catalytic (ie, catalyzes the conversion of cannabinoid carboxylated to a decarboxylated cannabinoid). The amount of acid can be at least about 0.01 gram (g), 0.1 g, 0.5 g, 1 g, 2 g, 5 g, 10 g, 20 g, 30 g, 40 g, 50 g, 60 g, 70 g, 80 g, 90 g, 100 g, or more.
[00104] The acid that can be used to convert a carboxylated cannabinoid to a decarboxylated cannabinoid can include one or more members selected from the group consisting of: lactic acid, citric acid, malic acid, acetic acid, benzoic acid, butyric acid, ascorbic acid, lactic acid, tartaric acid, tannic acid, and oxalic acid. An acid can be an edible acid. The acid may be naturally occurring, and may be isolated from a natural source, or it may be produced synthetically. Depending on which acid is
Petition 870190097797, of 9/30/2019, p. 47/284
40/68 used, the acid can be diluted (for example, with water) to provide an acidic solution having a pKa that may be suitable for converting a carboxylated cannabinoid to a decarboxylated cannabinoid.
[00105] The conversion can be carried out in a laboratory, in a production facility, in a residence, or in an office, and can be performed by a technician, a doctor, or by a buyer or user of a kit described here.
[00106] The conversion of a carboxylated cannabinoid to a decarboxylated cannabinoid can be under temperature conditions of a maximum of 500 ° C, 400 ° C, 300 ° C, 200 ° C, 100 ° C, 75 ° C, 50 ° C, 40 ° C, or 30 ° C. The conversion may not require an external heat source or additional heating to perform the reaction of a carboxylated cannabinoid to a decarboxylated cannabinoid.
[00107] Carboxylated cannabinoids can be converted to decarboxylated by contact of a carboxylated cannabinoid with an acid. This can be done by mixing, mixing, stirring, or any combination of these. Conversion can take place in a reaction vessel, such as, for example, a vat, a round bottom flask, a reactor, a batch reactor, a bond flow reactor, a catalytic reactor, a semi-batch reactor, or a household container. The reaction vessel can be configured to retain a reaction mixture. The reaction mixture can comprise an acid and part of a cannabis plant. The part of a cannabis plant may contain tetrahydrocannabinolic acid.
[00108] A reaction vessel can hold at least about 1 gram (g) of starting material, 2 g, 5 g, 10 g, 20 g, 30 g, 40 g, 50 g, 60 g, 70 g, 80 g, 90 g, 100 g, or more of starting material. The starting material can be part of a cannabis plant. The cannabis plant may contain carboxylated cannabinoids. The part of a plant
Petition 870190097797, of 9/30/2019, p. 48/284
41/68 cannabis can contain at least about 1 g, 2 g, 5 g, 10 g, 20 g, 30 g, 40 g, 50 g, 60 g, 70 g, 80 g, 90 g, 100 g or more of tetrahydrocannabinolic acid. A reaction vessel can hold at least about 1 milliliter (mL) in volume, 2 mL, 5 mL, 10 mL, 20 mL, 30 mL, 40 mL, 50 mL, 60 mL, 70 mL, 80 mL, 90 mL , 100 mL, 1 liter (L), 2 L, 5 L, 10 L, 50 L, 100 L, 1000 L, or more. A reaction vessel can be configured to provide production of at least about 1 gram (g) of a decarboxylated cannabinoid compound, 2 g, 5 g, 10 g, 20 g, 30 g, 40 g, 50 g, 60 g , 70 g, 80 g, 90 g, 100 g, or more than a decarboxylated cannabinoid compound.
[00109] A reaction mixture can withstand separation after the reaction is completed or near completion. The separation of the desired decarboxylated cannabinoids from the remainder of the reaction mixture, such as solvent, catalyst, plant material, or unconverted starting material, may include filtration, extraction, centrifugation, solubilization, concentration, washing, electrolysis, adsorption , purification, chromatography, fractionation, crystallization, or a combination of these. In some cases, the desired decarboxylated cannabinoid (for example, Δ ⁹ tetrahydrocannabinol), is separated from the reaction mixture, via 1, 2, 3, 4, 5 or more separation steps or procedures.
[00110] A trace amount of acid may be present in the reaction mixture after the reaction of a carboxylated cannabinoid to a decarboxylated cannabinoid. A trace amount of acid may be present after isolating the desired compound from the reaction mixture. The separated or isolated decarboxylated cannabinoid can be the desired end product that can be used in production processes for distribution to a user. The decarboxylated cannabinoid alone may comprise a trace amount of acid. A trace amount of acid can be less than about
Petition 870190097797, of 9/30/2019, p. 49/284
42/68 ca 10,000 parts per million (ppm), 1000 ppm, 100 ppm, 10 ppm, or 1 ppm.
Indications [00111] Terpenoids can have a beneficial effect on an individual. Terpenoids can be formulated into a composition described herein, and given to an individual as a nutritional supplement or a dietary supplement. A composition can provide nutrients or compounds that might otherwise not be consumed in sufficient quantities in a normal diet. A composition can contain compounds that can be beneficial to an individual's health, physical well-being, and emotional well-being. For example, a composition can be used as an energy boost.
[00112] A composition of the present disclosure can be used to treat or lessen the symptoms of nausea or vomiting. An individual who is administered a unit dose of a composition may experience a decrease in symptoms related to nausea or vomiting. [00113] A composition of the present disclosure can be used to treat an eating disorder, such as anorexia, cachexia, bulimia nervosa, rumination disorder, avoid pain or restrictive eating disorder.
[00114] A composition of the present disclosure can be used as a sleep aid to help with insomnia symptoms. A composition can help an individual to relax, fall asleep faster, improve the amount of sleep, or improve the quality of sleep.
[00115] A composition of the present disclosure can be used to mediate, limit, and reverse the effects of oxidative damage or oxidative stress. The reactive oxygen species imbalance within an individual can be corrected or mediated with administration of a composition described herein.
Petition 870190097797, of 9/30/2019, p. 50/284
43/68 [00116] Oxidative stress can occur before, during, and / or after surgery. Oxidative stress can be due to anesthesia used during surgery, surgical trauma, psychological stress associated with surgery, or a combination of these. A composition can be administered to an individual before, during, or after surgery. A composition can be administered to relieve traumatic shock that can be caused by surgery or injury.
[00117] Oxidative stress can be caused by a physical stress factor or an emotional stress factor. A composition of the present disclosure can be used to treat post-traumatic stress disorder (PTSD). Some symptoms of PTSD that can be relieved by a composition include: flashbacks, bad dreams, frightening thoughts, prevention of certain thoughts or feelings, being easily frightened, feeling tense, having difficulty sleeping, symptoms of cognition or mood, such as characteristics to remember the problem of the traumatic event, distorted feelings, such as guilt or responsibility, and loss of interest in fun activities.
[00118] A composition can be administered to prevent or limit the severity of development of posttraumatic stress disorder. The composition can be administered after physical or emotional stress, such as, for example, after a physical sport, a contact sport, physical combat, physical confrontation, and military combat.
[00119] A composition of the present disclosure can be used to treat, alleviate, or cease symptoms of addiction, addictive behavior, physical addiction, or psychological addiction. Addiction can be characterized by compulsive engagement in the stimulus. Addiction can be classified based on a severity index, such as the severity of addiction index (ASI). The ratings of
Petition 870190097797, of 9/30/2019, p. 51/284
44/68 ASi severity can be based on a 10 point scale, from 0-9. A rating of 0 - 1 can be classified as a non-real problem, treatment not indicated. A rating of 2 - 3 can be classified as a mild treatment problem and may not be indicated. A rating of 4 - 5 can be classified as a moderate problem, and some treatment can be indicated. A rating of 6 - 7 can be a considerable problem, and treatment may be necessary. A rating of 8 - 9 can be considered an extreme problem, and treatment may be absolutely necessary.
[00120] Examples of drug and behavioral addictions include, but are not limited to, alcoholism, addiction to cocaine, addiction to smoking, addiction to nicotine, addiction to opiate, addiction to food, addiction to amphetamine, and addiction to gambling.
[00121] A composition described here can be used to alleviate addiction to smoking. A composition can be used as part of a smoking cessation program, where the individual is given cannabinoid-infused tobacco. A composition can also be administered via water-soluble methods, to allow absorption of the membrane for natural and gradual decrease in addition. In addition, a composition described herein can contribute to anti-anxiety effects. For example, a composition administered in water-soluble form can provide rapid anti-anxiety effects to control addiction, via absorption from the mucous membrane. A cannabinoid composition can be part of a program to decrease tobacco use over time.
[00122] In some cases, a cannabinoid compound may have multiple bell curves of effectiveness. The effectiveness bell curves can change or modulate on a daily basis depending on a number of factors of the individual, including oxidative stress.
[00123] A composition of the present disclosure can be administered
Petition 870190097797, of 9/30/2019, p. 52/284
45/68 to an individual during and / or after treatment. An individual may experience a decrease in symptoms or a decrease in severity rating according to a severity index scale (for example, the ASI severity index).
[00124] A composition can be used to treat cancer or a tumor. Cancers that are liquid tumors can be those that occur, for example, in the blood, bone marrow, and lymph nodes, and can include, for example, leukemia, myeloid leukemia, lymphocytic leukemia, lymphoma, Hodgkin's lymphoma, melanoma, and myeloma multiple. Leukemias include, for example, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), and hair cell leukemia. Cancers that are solid tumors include, for example, prostate cancer, testicular cancer, breast cancer, brain cancer, pancreatic cancer, colon cancer, thyroid cancer, stomach cancer, lung cancer, ovarian cancer, sarcoma of Kaposi, skin cancer, scaly cell skin cancer, kidney cancer, head and neck cancers, throat cancer, squamous carcinomas that form in the moist gastric mucosa of the nose, mouth, throat, bladder cancer, osteosarcoma, cervical cancer , endometrial cancer, esophageal cancer, liver cancer, and kidney cancer. A composition described herein can be used to treat cervical cancer.
[00125] A composition described here can be used to treat prostate cancer. An individual can be assessed based on a level of prostate-specific antigen, or PSA, a protein produced by prostate gland cells. Elevated blood levels of PSA may be associated with individuals with prostate cancer.
[00126] A composition can be administered to an individual who has been diagnosed with prostate cancer. In some cases, a
Petition 870190097797, of 9/30/2019, p. 53/284
The composition can be administered to an individual with a PSA greater than about 1 monogram per milliliter (ng / mL), 2 ng / mL, 3 ng / mL, 4 ng / mL, 5 ng / mL, or 6 ng / mL, or higher. Administration with a composition may have a holidic dosage after an individual's PSA level is below a certain threshold. In some cases, a holidic dosage may begin after the PSA drops below about 20 nanograms per milliliter (ng / mL), 10 ng / mL, 5 ng / mL, 4 ng / mL, 3 ng / mL, 2 ng / ml, or 1 ng / ml. A holidium dosage of a composition can be replaced with another compound or composition. For example, an amount of delta-9-tetrahydrocannabinol (THC) can be administered during a holidic dosage of a composition described herein. The amount of THC administered can be a maximum of about 50 mg / kg, 40 mg / kg, 30 mg / kg, 20 mg / kg, 10 mg / kg, 5 mg / kg, 4 mg / kg, 3 mg / kg , 2 mg / kg, 1 mg / kg, or less.
[00127] A composition of the present disclosure can be used to treat an eating disorder or a weight disorder, such as, for example, anorexia and cachexia. Individuals may observe an increase in appetite after at least one unit dose of a composition of the present disclosure. In some cases, Δ ⁹ tetrahydrocannabinol in a composition can result in an appetite-enhancing effect with a unit dose of at least 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 10 mg, 15 mg, or 20 mg . An increase in appetite can continue for an extended period of time, such as at least 1 day, 2 days, 5 days, 7 days, 1 week, 2 weeks, 1 month, 3 months, 6 months, or 12 months after the last unit dose of a composition to be taken.
[00128] A composition of the present disclosure can be used to treat a muscle related disorder or a movement disorder, such as, for example, spasticity, tremor, ataxia, bladder control, Tourette's syndrome, dystonia, Parkinson's disease,
Petition 870190097797, of 9/30/2019, p. 54/284
47/68 Huntington's disease, and tardive dyskinesia. Spasticity may have been caused by pain, bone or joint deformities, or accidents or spinal injuries.
[00129] A composition of the present disclosure can be used to treat pain. Pain can be acute pain. The pain can be chronic pain. Pain can be associated with an illness. The pain in an individual can be neuropathic pain, menstrual pain, chronic headaches, or back pain. The pain may be due to an illness or disorder, or it may be caused by injury. The pain can be caused by a disease such as cancer, chronic intestinal inflammation, neuralgia, damaged nerves, diabetes, multiple sclerosis, an infection, or old age.
[00130] Pain may be nociceptive pain (ie pain caused by tissue damage), neuropathic pain, or psychogenic pain. The pain can be caused by or associated with a disease (for example, cancer, arthritis, diabetes). Alternatively, the pain is caused by injury (for example, sports injury, trauma). Non-limiting examples of pain that may be susceptible to treatment with the compositions and methods here include: neuropathic pain including peripheral neuropathy, diabetic neuropathy, post-herpetic nephralgia, trigeminal neuralgia, back pain, cancer-associated neuropathy, HIV-associated neuropathy / AIDS, fictitious limb pain, carpal tunnel syndrome, post-stroke central pain, pain associated with chronic alcoholism, hypothyroidism, uremia, pain associated with multiple sclerosis, pain associated with spinal cord injury, pain associated with Parkinson's disease, epilepsy, osteoarthritic pain, rheumatoid arthritic pain, visceral pain, and pain associated with vitamin deficiency; and nociceptive pain including pain associated with trauma to the central nervous system, strains / sprains, and burns; myocardial infarction, acute pancreatitis, postoperative pain, post-traumatic pain, renal colic, associated pain
Petition 870190097797, of 9/30/2019, p. 55/284
48/68 with cancer, pain associated with fibromyalgia, pain associated with carpal tunnel syndrome, and back pain.
[00131] The compositions and methods described herein can be used to improve a level of pain in an individual. A level of pain in an individual can be improved by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40% at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% at least 95%, at least 99% or 100%. A level of pain in an individual can be assessed by a variety of methods. A level of pain can be assessed by self-report (that is, a human individual expresses a verbal report of the level of pain he / she is experiencing). A level of pain can be assessed by behavioral indicators of pain, for example, facial expressions, limb movements, vocalization, restlessness and safeguard. These types of assessments can be useful, for example, when an individual is unable to self-report (for example, a child, an unconscious individual, a non-human individual). A level of pain can be assessed after treatment with a composition of the present disclosure, as compared to the level of pain the individual was experiencing before treatment with the composition.
[00132] A composition of the present disclosure can be used to reduce intraocular pressure or fluid pressure in the eye, and can be used to treat a number of diseases associated with abnormal intraocular pressure, including, but not limited to, glaucoma, iritis, detachment retinal. A composition can decrease intraocular pressure by 5%, 10%, 20%, 30%, 40%, 50%, or more.
[00133] The methods and compositions of the present disclosure can be used to treat epilepsy. The compositions described here
Petition 870190097797, of 9/30/2019, p. 56/284
49/68 can be used to prevent or control epileptic seizures. Epileptic seizures can be classified as tonic-clonic, tonic, clonic, myoclonic, absence or atonic attacks. The compositions and methods here can prevent or reduce the number of epileptic attacks experienced by an individual by at least about 5%, about 10%, about 15%, about 20%, about 25%, about 30% , about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80% , about 85%, about 90%, about 95%, about 99%, or higher.
[00134] The methods and compositions of the present disclosure can be used to relieve the symptoms of an inflammatory disease of the airways of the lungs, or asthma. The compositions can reduce the severity of asthma symptoms, or change in the severity of classification, such as from severe persistent, to moderate persistent, to mild persistent, to intermittent.
[00135] A composition of the present disclosure can be used to alleviate symptoms associated with withdrawal from alcohol and drug addiction, such as benzodiazepines and opiates. The composition can relieve withdrawal symptoms such as sleep disturbance, irritability, increased tension, anxiety, panic attacks, tremors, sweating, difficulty concentrating, confusion, memory loss, weight loss or weight gain, headaches , or muscle pain.
[00136] A composition of the present disclosure can be used to treat psychiatric disorders, including, but not limited to, sleep disorders, anxiety disorders, panic disorders, obsessive-compulsive disorders, bipolar disorder, depression, mood disorders, disorders personality disorders, psychotic disorders such as schizophrenia or delusional disorder. A composition can be used
Petition 870190097797, of 9/30/2019, p. 57/284
50/68 to treat a bipolar episode, in which a symptom may include an unusual change in mood, energy, activity level, and the inability to perform everyday tasks.
[00137] A composition of the present disclosure can be used to treat autoimmune diseases or inflammation, such as, but not limited to, arthritis, lupus, vitiligo, anemia, psoriasis, scleroderma, inflammatory bowel diseases, and type 1 diabetes.
[00138] The composition can be used to treat itching, ADS (attention deficit syndrome), high blood pressure, tinnitus, chronic fatigue syndrome, and restless loss syndrome.
[00139] The composition can be used to treat or relieve symptoms of hiccups or synchronous diaphragmatic palpitation (SDF). Hiccups can be classified as acute, chronic, persistent, or intractable. In some cases, a compound or composition can be used to treat or alleviate the symptoms of chronic hiccups.
[00140] A composition can be used to treat or relieve symptoms of menopause or pre-menopause. A composition can decrease the frequency and / or intensity of symptoms that include, for example, hot flashes, night sweats, pain during intercourse, increased anxiety or irritability, and the need to urinate more frequently.
[00141] A composition can be used to treat or sterilize wounds. A composition can be used in conjunction with citric acid, or it can be formulated into a composition for use in sterilizing open wounds.
[00142] A composition described herein can be used with poison or poison treatment. The composition can be administered before, during, or after administration of a poison antidote or an antivenom. The composition can be administered after exposure to a toxin or poison, and it can be in the absence of an antidote. The admin
Petition 870190097797, of 9/30/2019, p. 58/284
51/68 traction for use with a poison antidote can be via injection, sublingual, oral, via nasal spray, or a transdermal patch. Without wishing to be bound by theory, the cannabinoid composition can help protect the tissue, nervous system, and / or assist with the regulation of total homeostasis in the individual. The cannabinoid composition can adjust to decrease oxidative stress, tissue damage, organ damage, or neural trauma. The composition can also enhance cellular protection, health, and total homeostatic balance.
[00143] In some cases, a composition described herein may be used for the treatment of herpes zoster, rubella, measles, human papilloma virus (HPV), chronic obstructive pulmonary disease (COPD), emphysema, litigation, impetigo, pneumonia, listeria, Ebola, Addison's disease, Graves' disease, Sjögren's syndrome, Hashimoto's disease, autism, myasthenia gravis, Pernicious anemia, or celiac disease.
[00144] In some cases, a composition can be used to treat an autoimmune disease. In some cases, a composition can be used to treat Achalasia, Addison's disease, Adult's Still disease, Agammaglobulinemia, Alopecia areata, Amyloidosis, ankylosing spondylitis, Anti-GBM / Anti-TBM nephritis, Antiphospholipid syndrome, autoimmune angiodema, dysatonomy autoimmune, autoimmune encephalomyelitis, autoimmune hepatitis, autoimmune inner ear disease (AIED), autoimmune myocarditis, autoimmune oophoritis, autoimmune orchitis, autoimmune pancreatitis, autoimmune retinopathy, autoimmune urticaria, Axonal & neuronal neuropathy (BΑΜΑΝo) disease , benign mucous pemphigoid, bullous pemphigoid, Castleman's disease (CD), Celiac disease, Chagas disease, chronic inflammatory demyelination polyneuropathy (CIDP), chronic recurrent multifocal osteomyelitis (CRMO), Churg-Strauss syndrome (CSS) or Eosinophilic granulomatosis (EGPA), cicatricial pemphigoid, Cogan syndrome, cold agglutinin disease, Heart block with
Petition 870190097797, of 9/30/2019, p. 59/284
52/68 genital, Coxsackie myocarditis, CREST syndrome, Crohn's disease, Dermatitis herpetiformis, Dermatomyositis, Devic's disease (neuromyelitis optica), discoid lupus, Dressier syndrome, Endometriosis, Eosinophilic esophagitis (EoE), Eosinophilic faciitis , Essential mixed cryoglobulinemia, Evans syndrome, Fibromyalgia, Fibrous alveolitis, Giant cell arthritis (temporal arthritis), Giant cell myocarditis, Glomerulonephritis, Goodpasture syndrome, Granulomatosis with polyangiitis, Graves' disease, Guillain-Barre syndrome, Thyroiditis Hashimoto, Hemolytic anemia, Henoch-Schonlein purpura (HSP), Herpes gestatione ou gestationis penflgolde (PG), Hidradenitis Suppurativa (HS) (Acne Inversa), Hypogammalglobulinemia, IgA Nephropathy, scleral disease related to lgG4, mombura, purpura inclusion body (IBN), interstitial cystitis (HF), juvenile arthritis, juvenile diabetes, juvenile myositis (JM), Kawasaki disease, La syndrome mbert-Eaton, leukocytoclastic vasculitis, Lichen planus, Lichen sclerosus, Ligneous conjunctivitis, linear IgA disease (LAD), Lupus, chronic Lyme disease, Meniere's disease, Microscopic polyamgiitis (MPA), mixed connective tissue disease (MCOD), Mooren's ulcer, Mucha-Habermann's disease, Multifocal Motor Meuropathy (MMN) or MMNCB, Multiple sclerosis, Myasthenia gravis, Myositis, Narcolepsy, Neonatal lupus, Optic neuromyelitis, Neutropenia, Ocular pemphigoid, Optic neuritis, Rheumatism palindromy PANDAS, Paraneoplastic cerebellar degeneration (PCD), paraxismal nocturnal hemoglobinuria (PNH), Parry Romberg syndrome, Pars planitis (peripheral uveitis), Parsonnage-Turner syndrome, Pemphigus, Peripheral neuropathy, Pernicious anemia, POEMS syndrome, Polyarteritis nodose Polyglandular type I, II, III, Polymyalgia rheumatica, Polymyositis, posmiocardial infarction syndrome, pospericardiotomy syndrome, Primary sclerosing cholangitis, Dermatitis of Pro gesterone, Psoriasis, psoriatic arthritis,
Petition 870190097797, of 9/30/2019, p. 60/284
53/68
Pure red cell aplasia (PRCA), Grangenous pyoderma, Raynaud's phenomenon, Reactive arthritis, Sympathetic reflex dystrophy, Relapse polyondritis, Restless legs syndrome (RLS), Rheumatic fever, Rheumatoid arthritis, Sarcoidosis, Schmidt syndrome, Scleritis, Scleroderma, Sjogren's syndrome, Sperm & testicular autoimmunity, Rigid people syndrome (SPS), Subacute bacterial endocarditis (SBE), Susac's syndrome, Sympathetic ophthalmia (OS), Takayasu's arthritis, Temporal arthritis / giant cell arthritis, Syndrome Tolosa-Hunt (THS), Transverse Myelitis, Type 1 Diabetes, Ulcerative Colitis (UC), Undifferentiated Connective Tissue Disease (LJCTD), Uveitis, Vasculitis, Vitiligo, Vogt-Koyanagi-Harada Disease, or Wegener Granulomatosis ( or Granulomatosis with Polyangiitis (GPA)). [00145] A composition comprising cannabinoids can be formulated in water-soluble form. Administration of the composition in a water-soluble form may allow rapid membrane absorption. The composition can be added to a water supply, for example, drinking water, for protection after a chemical agent or toxicity or exposure event.
[00146] A composition can be used to enhance neurogenesis, or the growth and development of nerve tissue in an individual. A composition can also enhance the total performance of the nervous system, including the parasympathetic nervous system, the sympathetic nervous system, and the enteric nervous system.
[00147] A composition can be used as a supplement to protect a telomere, a region on the end of a chromosome in an individual. The protection of a telomere can protect the chromosome from deterioration.
[00148] In some cases, a composition described herein can be used as a targeted endocannabinoid system (ECB) therapeutic. Two primary system endocannabinoid receptors
Petition 870190097797, of 9/30/2019, p. 61/284
54/68 of endocannabinoids are CB1 and CB2.
[00149] In some cases, a composition of the present disclosure may be used in combination with epigenetics, or the study of inherited changes in gene function that may not involve changes in the DNA sequence, or functionally relevant changes to the genome that may not involve a change in the nucleotide sequence (for example, DNA methylation, histone modification). In some cases, epigenetic mechanisms can include factors and processes such as development (eg, in the womb, childhood), environmental factors (eg, environmental chemicals), drugs, pharmaceuticals, aging, and diet.
[00150] A composition can be administered or suggested based on epigenetic testing. In some cases, a composition described here can modulate risk factors or improve disease conditions. In some cases, terpenes, such as those described herein, can be used to target cannabinoids to specific CB receptor sites. The compounds disclosed herein can be used to prevent mitigating risks or damage during or after epigenetic indication, and can contribute to the change in expression.
[00151] In some cases, a composition can be used to treat the thyroid if a thyroid risk factor is apparent, then the same composition can be used to target a different region of the body using different terpenes if a new epigenetic expression has appeared . In some cases, a composition can have rapid absorption into the body. If a composition is rapidly absorbed, the same formula can be given sequentially, and can change the effects of cannabinoids.
[00152] In some cases, a composition can be administered or suggested based on genetic testing.
[00153] Alternatively, a composition can be administered
Petition 870190097797, of 9/30/2019, p. 62/284
55/68 based on the standard test for target treatment protocols, in which cannabinoids and terpenes in the composition can prevent and / or treat risk factors or disease states.
[00154] An individual may exhibit one or more symptoms. A symptom can be selected from pain, stress, nausea, vomiting, insomnia, anxiety, and loss of appetite. A unit dose can be used to relieve a symptom in an individual, and in some cases, by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80 %, 85%, 90%, 95%, or 99%. A composition can result in a decrease in the severity or amount of symptoms by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90% , 95%, or 99%.
[00155] A unit dose can be administered at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more times daily. An individual can receive dosing for a period of about, less than about, or more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or more days, weeks or months. A unit dose can be a fraction of the daily dose, as well as the daily dose divided by the number of unit doses to be administered per day. A unit dose can be a fraction of the daily dose which is the daily dose divided by the number of unit doses to be administered per day and further divided by the number of unit doses (for example, tablets) per administration. The number of unit doses per administration can be at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more. The number of doses per day can be at least 1,2, 3, 4, 5, 6, 7, 8, 9, 10, or more. The number of unit doses per day can be determined by dividing the daily dose by the unit dose, and can be at least 1, 2, 3, 4. 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 6, 17, 18, 19, 20, or more unit doses per day. For example, a unit dose can be about 1/2, 1/3, 1/4, 1/5, 1/6, 1/7, 1/8, 1/9, or 1/10 of the recommended daily dose.
Petition 870190097797, of 9/30/2019, p. 63/284
56/68 given. A unit dose can be about one third of the daily amount and administered to the individual three times a day. A unit dose can be about half the daily amount and administered to the subject twice a day. A unit dose can be about a quarter of the daily amount with two unit doses administered to the individual twice a day.
[00156] The length of the administration period and / or the dosage amounts can be determined by a doctor or any other type of clinician. The doctor or clinician can observe the individual's response to the administered compositions and adjust the dosage based on the individual's performance. For example, the dosage for individuals who show reduced effects on energy regulation can be increased to achieve desired results.
[00157] The components in the compositions can be administered together at the same time on the same route, or administered separately. The components in the compositions can also be administered subsequently. The components in the compositions can be administered in the same or different route of administration.
[00158] Another aspect of the present disclosure provides for achieving desired effects in one or more individuals after administration of a combination of the composition described herein for a specified period of time. For example, the beneficial effects of the compositions described herein can be observed after administration of the compositions to individuals for 1.2, 3, 4, 6, 8, 10, 12, 24, or 52 weeks.
[00159] In some embodiment, the present disclosure also provides methods of manufacturing the compositions described herein. The manufacture of a composition described herein can comprise mixing or combining two or more components.
[00160] The compositions can be combined or mixed with
Petition 870190097797, of 9/30/2019, p. 64/284
57/68 an active or therapeutic pharmaceutical agent, a carrier, and / or an excipient. Examples of such components are described herein. The combined compositions can be formed in a unit dosage such as tablets, capsules, gel capsules, or slow-release tablets.
[00161] The composition can be prepared such that a solid composition containing a substantially homogeneous mixture of the one or more components is achieved, such that the one or more components are uniformly dispersed throughout the composition so that the composition can be readily subdivided in equally effective unit dosage forms such as tablets, pills and capsules.
[00162] A unit dose of a composition can retain at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of one or more cannabinoids after placing in a sealed container for a certain period of time, such as after 1 day, 7 days, 1 month, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more. A unit dose of a composition can have a useful life that is at least about 1 day, 7 days, 1 month, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more. Without wishing to be bound by theory, a trace amount of acid in a composition can contribute and enhance the life of a composition.
[00163] A unit dose of a composition can be stored under conditions of at least about 25 ° C, 30 ° C, 40 ° C, 50 ° C, 60 ° C, 70 ° C, or more. A unit dose of a composition can be stored under a moisture level condition of at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or more humidity level without significant cannabinoid degradation.
[00164] A unit dose can be packaged in a container to be transferred to the user. A unit dose can be packaged in
Petition 870190097797, of 9/30/2019, p. 65/284
58/68 a tube, a jar, a box, a bottle, a bag, a tray, a drum, a bottle, a syringe, or a can.
Kits [00165] The present disclosure also provides kits. The kits include one or more compositions described here, in suitable packaging, and may additionally comprise written material that may include Instructions for use, discussion of clinical studies, and listing of side effects. Such kits may also include information, such as scientific literature references, packaging insert materials, clinical trial results, and / or summaries thereof, which indicate or establish the activities and / or advantages of the composition, and / or which describe dosage , administration, co-material effects, drug interactions, or other information useful to the health care provider. Such information can be based on the results of several studies, for example, studies using experimental animals involving in vivo models and studies based on human clinical trials. A kit may comprise one or more unit doses described herein. A kit can comprise at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 31, 60, 90, 120, 150, 180, 210, or more unit doses. A kit can comprise at most about 20, 15, 10, 5, 4, 3, 2, or 1 unit dose. Instructions for use may comprise dosing instructions, such as instructions for taking 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more unit doses 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more times a day. For example, a kit may comprise a unit dose supplied as one tablet, with each tablet packaged separately, multiple tablets packaged separately according to the number of unit doses per administration (for example, pairs of tablets), or all tablets packaged together ( for example, in a bottle). As an additional example, a kit may comprise a unit dose above
Petition 870190097797, of 9/30/2019, p. 66/284
59/68 as a bottled drink, the kit comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 24, 28, 36, 48, 72, or more bottles.
[00166] Instructions can be provided in printed form on a user interface of a user's electronic device. Instructions can be provided, for example, in a graphical user interface, or a web-based interface.
[00167] The kit may additionally contain another agent. The compound of the present disclosure and the agent can be provided or packaged as separate compositions in separate containers within the kit. The compound of the present disclosure and the agent can be provided or packaged as a single composition within a container in the kit. Suitable packaging and additional items for use (eg measuring cup for liquid preparations, foil wrap to minimize exposure to air) can be included in the kit. The kits described here can be provided, marketed and / or promoted to healthcare providers, including doctors, nurses, pharmacists, form employees. The kits can also be sold directly to the consumer.
[00168] A kit may comprise a multi-day supply of unit doses. Unit dosages can be any unit dosage described herein. The kit may comprise instructions aimed at administering the supply of many days of unit dosages over a period of multiple days. The multi-day supply can be a one-day supply, a 30-day supply, or a many-week supply. The multi-day supply can be a 90-day supply, 180-day supply, 3-month supply, or 6-month supply. The kit may include daily packaged unit doses, such as packs of 1, 2, 3, 4, or 5 unit doses. The kit can be packaged with other dietary supplements, vitamins, and meal replacement bars, mixes, and be
Petition 870190097797, of 9/30/2019, p. 67/284
60/68 bidas.
[00169] A kit can comprise starting materials that allow a user to convert a carboxy cannabinoid to a decarboxylated cannabinoid (for example, Δ ⁹ tetrahydrocannabinol).
[00170] A kit can comprise all the necessary starting materials so that a user can perform the conversion. The kit may comprise a carboxy cannabinoid, an acid present to convert the carboxy cannabinoid to a decarboxylated cannabinoid, a reaction vessel configured to retain a reaction mixture comprising the acid and the carboxy cannabinoid, and instructions for performing the conversion using the acid . The resulting decarboxylated cannabinoid that is formed from the conversion can be Δ ⁹ tetrahydrocannabinol.
[00171] Alternatively, a kit can comprise some of the necessary starting materials so that a user can perform the conversion. A user can supplement the kit with his own supply of carboxy cannabinoids. The kit may comprise an acid present to convert the carboxy cannabinoid to a decarboxylated cannabinoid, a reaction vessel configured to retain a reaction mixture comprising the acid and the carboxy cannabinoid, and instructions for performing the conversion using the acid. The carboxy cannabinoid that the user supplies may be tetrahydrocannabinolic acid.
[00172] The acid in a kit can be present in at least about 0.01 gram (g), 0.1 g, 0.5 g, 1 g, 2 g, 5 g, 10 g, 20 g, 30 g, 40 g, 50 g, 60 g, 70 g, 80 g, 90 g, 100 g, or more.
[00173] The carboxy cannabinoid (e.g. tetrahydrocannabinolic acid), if provided in a kit, can be present in at least about 1 gram (g), 2 g, 5 g, 10 g, 20 g, 30 g, 40 g , 50 g, 60 g,
Petition 870190097797, of 9/30/2019, p. 68/284
61/68 g, 80 g, 90 g, 100 g, or more. The amount of decarboxylated cannabinoid formed from carrying out a reaction using a kit can be at least about 1 gram (g), 2 g, 5 g, 10 g, 20 g, 30 g, 40 g, 50 g, 60 g, 70 g, 80 g, 90 g, 100 g, or more.
Computer Control Systems [00174] The present disclosure provides computer control systems that are programmed to implement the methods of the disclosure. FIG. 1 shows a computer control system 101 that is programmed or otherwise configured to produce a composition comprising a mixture of carboxylated cannabinoids and decarboxylated cannabinoids, or provide instructions for use or generation of compositions of the present disclosure. The computer control system 101 can regulate various aspects of the methods of the present disclosure, such as, for example, methods of producing decarboxylated cannabinoids, including, but not limited to, the movements of the reaction vessel and shaker, packing a dose of a composition, and printing instructions for using a composition. Computer control system 101 can be implemented in a user's electronic device, or a computer system that is remotely located with respect to the electronic device. The electronic device can be a mobile electronic device.
[00175] Computer system 101 includes a central processing unit (CPU, also "processor" and "computer processor" here) 105, which can be a single-core or multi-core processor, or a plurality of processors for parallel processing. Computer control system 101 also includes memory or memory location 110 (for example, random access memory, read-only memory, instant memory), electronic storage unit 115 (for example, hard disk),
Petition 870190097797, of 9/30/2019, p. 69/284
62/68 communication interface 120 (for example, network adapter) for communication with one or more other systems, and peripheral devices 125, such as cache, other memory, data storage and / or electronic display adapters. Memory 110, storage unit 115, interface 120 and peripheral devices 125 are in communication with CPU 105 via a communication bus (solid lines), such as a motherboard. The storage unit 115 can be a data storage unit (or data repository) for data storage. The computer control system 101 can be operably coupled to a computer network (“network”) 130 with the aid of the communication interface 120. The network 130 can be the Internet, an internet and / or extranet, or an intranet and / or extranet that is communicating with the Internet. Network 130, in some cases, is a telecommunication network and / or data network. Network 130 may include one or more computer servers, which can enable distributed computing, such as cloud computing. Network 130, in some cases, with the aid of computer system 101, can implement a point-to-point network, which can enable devices coupled to computer system 101 to behave like a client or a server.
[00176] CPU 105 can execute a sequence of machine-readable instructions, which can be implemented in a program or software. Instructions can be stored in a memory location, such as memory 110. Instructions can be directed to CPU 105, which can subsequently program or otherwise configure CPU 105 to implement methods of the present disclosure. Examples of operations performed by CPU 105 may include fetch, decode, execute, and writeback.
[00177] CPU 105 may be part of a circuit, such as an integrated circuit. One or more other components of the 101 po system
Petition 870190097797, of 9/30/2019, p. 70/284
63/68 must be included in the circuit. In some cases, the circuit is an application-specific integrated circuit (ASIC).
[00178] The storage unit 115 can store files, such as drivers, libraries, and saved programs. The storage unit 115 can store user data, for example, user preferences and user programs. Computer system 101, in some cases, may include one or more additional data storage units that are external to computer system 101, such as located on a remote server that is communicating with computer system 101 via a intranet or the Internet.
[00179] Computer system 101 can communicate with one or more remote computer systems over network 130. For example, computer system 101 can communicate with a user's remote computer system (for example, a user controls the manufacture of a three-dimensional object). Examples of remote computer systems include personal computers (for example, portable PC), slate or tablet PCs (for example, Apple® iPad, Samsung® Galaxy Tab), phones, Smart phones (for example, Apple® iPhone, Android-enabled device, Blackberry®), or personal digital assistants. The user can access computer system 101, via network 130.
[00180] The methods as described herein can be implemented by executable code per machine (for example, computer processor) stored in an electronic storage location of computer system 101, such as, for example, in memory 110 or unit electronic storage 115. The executable machine or machine-readable code can be provided in the form of software. During use, the code can be executed by processor 105. In some cases, the code can be retrieved
Petition 870190097797, of 9/30/2019, p. 71/284
64/68 from storage unit 115 and stored in memory 110 for ready access by processor 105. In some situations, electronic storage unit 115 may be prevented, and machine executable instructions are stored in memory 110.
[00181] The code can be precompiled and configured for use with a machine having a processor adapted to execute the code, or it can be compiled during the excision time. The code can be supplied in a programming language that can be selected to enable the code to run in a pre-compiled or compiled mode.
[00182] Aspects of the systems and methods provided here, such a computer system 101, can be realized in programming. Various aspects of technology can be considered as "products or" articles of manufacture "typically in the form of code executable by machine (or processor) and / or associated data that is conveyor or materialized in a type of machine-readable medium. Machine executable code can be stored in an electronic storage unit, such as memory (for example, read-only memory, random access memory, instant memory), or a hard drive. “Storage” media can include any or all of the computers, processors or similar tangible memory, or associated modules, such as various semiconductor memories, tape drives, hard drives, and the like, which can provide non-transitory storage in any time for software programming. All or portions of the software can sometimes be communicated via the Internet or several other telecommunication networks. Such communications, for example, can enable software to be loaded from one computer or processor to another, for example, from a control server or with
Petition 870190097797, of 9/30/2019, p. 72/284
65/68 host puter on the computer platform of an application server. Thus, another type of medium that may be the software elements includes optical, electrical and electromagnetic waves, such as used through physical interfaces between local devices, through fixed wired and optical networks, and over various aerial connections. The physical elements that carry such waves, such as wired or wireless connections, optical connections, or the like, can also be considered as a medium that supports the software. As used herein, unless restricted to tangible, non-transitory "storage" medium, terms such as "machine-readable medium" refer to any medium that participates in providing instructions to a processor for execution.
[00183] Consequently, a machine-readable medium, such as computer executable code, can take many forms, including, but not limited to, a tangible storage medium, a carrier wave medium or physical transmission medium. Non-volatile storage media include, for example, optical or magnetic disks, such as any of the storage devices on any computer (s) or the like, as can be used to implement the databases, etc. shown in the drawings. Volatile storage media include dynamic memory, such as main memory on such a computer platform. Tangible means of transmission include coaxial cables; copper wires and optical fibers, including wires that comprise a bus within a computer system. Carrier wave transmission media can take the form of electrical or electromagnetic signals, or acoustic or light waves, such as those generated during radio frequency (RF) and infrared (IR) data communication. Common forms of computer-readable media, therefore, include, for example: a floppy disk, a floppy disk, hard disk, magnetic tape, any other
Petition 870190097797, of 9/30/2019, p. 73/284
66/68 magnetic medium, a CD-ROM, DVD or DVD-ROM, any other optical medium, perforated cards, paper tape, any other physical storage medium with hole patterns, a RAM, a ROM, a PROM and EPROM , a FLASH-EPROM, any other chip or memory cartridge, a carrier wave transport data or instructions, cables or connections that carry such a carrier wave, or any other means by which a computer can read programming code and / or Dice. Many of these forms of computer-readable medium can be involved in transporting one or more sequences of one or more instructions to a processor for execution.
Examples [00184] EXAMPLE 1: Pain Relief Treatment for an Individual with Chronic Pain with a Composition [00185] Individuals (for example, patients) who are suffering from chronic pain have their pain levels accessed and evaluated by a primary care physician. treatment or other pain management expert. Such Individuals are then prescribed 10 mg / day of a composition comprising cannabinoids and one or more terpenoids. The subjects are then evaluated again after two weeks to determine whether the symptoms have improved. After evaluation, the dosage is increased, decreased, or maintained depending on the change in the level of pain. Treatment is maintained as long as necessary to affect a stable resolution of chronic pain symptoms.
[00186] EXAMPLE 2: Treatment of an Individual Who Has Been Diagnosed with Alzheimer's Disease [00187] Individuals who are clinically diagnosed with Alzheimer's disease are evaluated for common symptoms, such as memory loss and confusion.
[00188] Individuals are prescribed 10 mg / day of a composition, and then evaluated again after two weeks to
Petition 870190097797, of 9/30/2019, p. 74/284
67/68 determine whether symptoms worsened. After evaluation, the dosage is increased, decreased, or maintained depending on the change in symptoms of inattention and hyperactivity. Treatment is maintained as long as necessary to affect a stable or desired level of symptoms of Aizheimer disease.
[00189] EXAMPLE 3: Synthesis of a Unit Dose of a Composition [00190] A reaction vessel in an industrial laboratory is placed in an ice bath. The reaction vessel is loaded with 100 grams of cannabis plant, 1 mL of acetic acid, and 5 L of water. The reaction is stirred as the ice bath is removed and the reaction is allowed to go to room temperature.
[00191] After the reaction is completed after 30 minutes, the reaction mixture is filtered and the water in the resulting solution is removed. The solid is then mixed with a filler, such as gelatin, and is packed in a capsule as a unit dose.
[00192] The unit dose is then distributed and sold to users.
[00193] EXAMPLE 4: User Synthesis of a Unit Dose of a Composition Using a Kit [00194] A kit is sold to a user. The kit comprises all the necessary starting materials so that the user can convert a carboxylated cannabinoid to a decarboxylated cannabinoid. The kit comprises 2 grams of a cannabis plant, 1 gram of citric acid, a vat, and instructions for performing the conversion using the acid.
[00195] The user follows the instructions and places the cannabis plant and citric acid in the vat. The user then adds 1 glass of water, according to the instructions provided in the kit. The mixture is stirred for 5 minutes to complete the reaction.
Petition 870190097797, of 9/30/2019, p. 75/284
68/68 [00196] Methods and compositions provided herein can be combined with other methods and compositions, such as those described in PCT Patent Publication No. WO / 2016/094810, which is fully incorporated herein by reference.
[00197] While preferred embodiments of the present invention have been shown and described here, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. The invention is not expected to be limited by the specific examples provided within the specification. While the invention has been described with reference to the aforementioned specification, the descriptions and illustrations of the embodiments here are not significant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without evading invention. In addition, it should be understood that all aspects of the invention are not limited to the specific representations, configurations or relative proportions placed here that depend on a variety of conditions and variables. It should be understood that several alternatives to the embodiments of the invention described herein can be employed in the practice of the invention. It is, therefore, contemplated that the invention must also cover any such alternatives, modifications, variations, or equivalents. It is envisaged that the following claims define the scope of the invention, and that methods and structures within the scope of these claims and their equivalents are thereby covered.

权利要求:
Claims (51)
[1]
1. Unit dose, characterized by the fact of understanding:
(i) a mixture of carboxylated cannabinoids and decarboxylated cannabinoids, and (ii) one or more terpenoids, in which a weight / weight ratio of decarboxylated cannabinoids to carboxylated cannabinoids is greater than 0.5, and in which said unit dose is substantially free of terpenoid degrading compounds.
[2]
2. Unit dose according to claim 1, characterized by the fact that it comprises at least 5 mg of decarboxylated cannabinoids.
[3]
3. Unit dose according to claim 1, characterized by the fact that said decarboxylated cannabinoids comprise Δ ⁹ tetrahydrocannabinol.
[4]
4. Unit dose, according to claim 1, characterized by the fact that referred to one or more terpenoids is selected from the group consisting of: mycrene, iimonene, linalool, trans-ocimene, eta-pinene, a / fa-pinene , beta-karyophylene, delta-3carene, trans-gamme-bisabolene, trans-a / fa-farnesene, befa-fenchol, a / fa-humulene, and guajol.
[5]
5. Unit dose, according to claim 1, characterized by the fact that one or more terpenoid degrading compounds are selected from the group consisting of: geraniol, geranyl isobutyrate, p-cimenene, p ~ cimen, p ~ mint-1,5,8-triene, carvone, 3-methyl-6- (1-methylethylidene) ~ 2 ~ cyclohexen-1-one, 3-methyl-6- (1 methylethyl) -2 ~ cyclohexen-1-one , eucarvona, thymol, p-mint-1 (7), 8-dien-
2-ol, perylyl alcohol, camphene, beta-myrcene, a / fa-phelandreno, a / faterpinene, gamma-terpinene, terpinolene, 4-hydroxy-2-methyl-2cyclohexenone, p-cimenene, o-cymene, 3-caren -2-one, 3-caren-5-one,
Petition 870190097797, of 9/30/2019, p. 77/284
2/9
Carene 3-oxide, 3-carene-2,5-dione, trans-2-hydroxy ”3-caren-5-one, thymol, carvacrol, 1,4-cíneoie, eucalyptol, 3 ~ (1-methylethyl) - 6-oxo ~ 2 ~ heptenal, and 3,7-dimethyl6-oxo-2-octenal,
[6]
6. Unit dose according to claim 1, characterized by the fact that it additionally comprises a trace amount of an acid.
[7]
Unit dose according to claim 1, characterized in that it additionally comprises a pharmaceutically acceptable excipient.
[8]
8. Unit dose according to claim 7, characterized in that said pharmaceutically acceptable excipient is selected from the group consisting of: a binder, a filler, a plasticizer, a lubricant, an anti-foaming agent, an agent buffering agent, a polymer, an antioxidant, a preservative, a chelating agent, a flavoring, a dye, an odoriferous, a suspending agent, and a combination of these.
[9]
9. Unit dose according to claim 1, characterized in that said unit dose is formulated for oral administration, topical administration, administration by inhalation, intravenous administration, or intramuscular administration.
[10]
10. Unit dose, according to claim 1, characterized by the fact that said unit dose is in solid form.
[11]
11. Unit dose, according to claim 1, characterized by the fact that said unit dose is in liquid form.
[12]
12. Unit dose, according to claim 1, characterized in that said unit dose is a tablet, a chewable tablet, a capsule, a pill, a granule, an emulsion, a gel, a spray, a plurality of drops encapsulated in a capsule, powder, suspension, liquid, semi-liquid, semi-solid, solution, syrup, or slurry.
Petition 870190097797, of 9/30/2019, p. 78/284
3/9
[13]
13. Unit dose, according to claim 1, characterized by the fact that said unit dose retains at least 80% of said cannabinoids after being placed in a sealed container for 6 months at a temperature of about 25 ° C and a level of relative humidity of about 50%.
[14]
14. Unit dose, according to claim 1, characterized by the fact that said unit dose is packaged in a container selected from the group consisting of a tube, a jar, a box, a bottle, a bag, a tray, a drum, a bottle, a syringe, and a can.
[15]
15. Kit characterized by the fact that it comprises a unit dose according to claim 1, and instructions for supplementing said mixture of carboxylated cannabinoids and decarboxylated cannabinoids, and one or more terpenoids to an individual in need of these.
[16]
16. Kit for the preparation of Δ ⁹ tetrahydrocannabinol, characterized by the fact that it comprises:
(Ί) an acid present in an effective amount for converting at least 50% of tetrahydrocannabinolic acid to said Δ ⁹ tetrahydrocannabinol, (ΊΙ) a reaction vessel configured to retain a reaction mixture comprising said acid and said tetrahydrocannabinolic acid, and ( ΊΗ) instructions for performing said conversion using said acid.
[17]
17. Kit according to claim 16, characterized in that it additionally comprises tetrahydrocannabinolic acid.
[18]
18. Kit according to claim 16, characterized in that said acid is a weak acid.
Petition 870190097797, of 9/30/2019, p. 79/284
4/9
[19]
19. Kit according to claim 16, characterized in that said acid has a pKa of about 3 to about 7.
[20]
20. Kit according to claim 16, characterized by the fact that said acid is selected from the group consisting of: lactic acid, citric acid, malic acid, acetic acid, benzoic acid, ascorbic acid, tartaric acid, and acid oxalic,
[21]
21. Method of supplementing one or more cannabinoids and one or more terpenoids to an individual in need thereof, the method characterized by the fact that it comprises administering to that individual a unit dose comprising:
i. a mixture of carboxylated cannabinoids and decarboxylated cannabinoids, and ii. one or more terpenoids, in which a weight / weight ratio of decarboxylated cannabinoids to carboxylated cannabinoids is greater than 0.5, and in which said unit dose is substantially free of terpenoid degrading compounds.
[22]
22. Method, according to claim 21, characterized by the fact that said individual suffers from a symptom selected from the group consisting of: pain, stress, nausea, vomiting, insomnia, anxiety, and loss of appetite.
[23]
23. Method according to claim 21, characterized in that said unit dose is administered orally, topically, by inhalation, intravenously, or intramuscularly.
[24]
24. Method according to claim 21, characterized in that said unit dose is administered at least once a day.
[25]
25. Method, according to claim 21, characterized in that it additionally comprises monitoring a state
Petition 870190097797, of 9/30/2019, p. 80/284
5/9 health or condition of said individual subsequent to the administration of said unit dose to said individual.
[26]
26. Method of production of decarboxylated cannabinoids, characterized by the fact that it comprises:
(i) contacting a cannabis plant or a portion thereof with an acid to form a reaction mixture under effective conditions for converting the carboxylated cannabinoids present in said cannabis plant into decarboxylated cannabinoids; and (ii) separating said cannabis pianta or a portion thereof from said decarboxylated cannabinoids, thereby producing said decarboxylated cannabinoids.
[27]
27. Method according to claim 26, characterized in that said decarboxylated cannabinoids comprise Δ ⁹ tetrahydrocannabinol.
[28]
28. Method according to claim 26, characterized in that the weight / weight ratio of decarboxylated cannabinoids to carboxylated cannabinoids in said reaction mixture of (ii) is greater than 0.1.
[29]
29. Method according to claim 26, characterized in that said conditions are at a temperature of less than 300 ° C.
[30]
30. Method according to claim 28, characterized by the fact that external heating is not applied during said conversion of said carboxylated cannabinoids to said decarboxylated cannabinoids.
[31]
31. Method according to claim 26, characterized in that said acid is a weak acid.
[32]
32. Method according to claim 26, characterized by the fact that said contact comprises mixing, mixing, stirring, or a combination of these.
Petition 870190097797, of 9/30/2019, p. 81/284
6/9
[33]
33. Method, according to claim 26, characterized by the fact that said separation is selected from the group consisting of: filtration, extraction, centrifugation, solubilization, concentration, washing, electrolysis, adsorption, purification, chromatography, fractionation, crystallization , and a combination of these.
[34]
34. Mixture characterized by understanding:
(i) carboxylated cannabinoids and decarboxylated cannabinoids, (ii) one or more terpenoids, and (iii) an acid, in which a weight / weight ratio of decarboxylated cannabinoids to carboxylated cannabinoids is greater than 0.1, and in which referred acid is present in an amount effective in converting at least a portion of carboxylated cannabinoids into decarboxylated cannabinoids.
[35]
35. Mixture, in accordance with claim 34, characterized by the fact that said carboxylated cannabinoids comprise tetrahydrocannabinolic acid.
[36]
36. Mixture according to claim 33, characterized in that said mixture comprises at least 0.05 mol of said decarboxylated cannabinoids.
[37]
37. Mixture according to claim 33, characterized by the fact that said decarboxylated cannabinoids comprise Δ ⁹ tetrahydrocannabinol.
[38]
38. Mixture according to claim 37, characterized in that a weight / weight ratio of Δ ⁹ tetrahydrocannabinol to tetrahydrocannabinolic acid is greater than about 0.1.
Petition 870190097797, of 9/30/2019, p. 82/284
7/9
[39]
39. Mixture according to claim 33, characterized in that said mixture is substantially free of terpenoid degrading compounds.
[40]
40. Mixture according to claim 33, characterized by the fact that said acid is an organic acid.
[41]
41. Method for generating a decarboxylated cannabinoid formulation, characterized by the fact that it comprises:
(a) providing a reaction vessel comprising a mixture, in which said mixture comprises:
i. carboxylated cannabinoids and decarboxylated cannabinoids, ii. one or more terpenoids, and an acid, in which a weight / weight ratio of decarboxylated cannabinoids to carboxylated cannabinoids is greater than 0.1, and in which said acid is present in an effective amount in converting at least a portion from carboxylated cannabinoids to decarboxylated cannabinoids; and (b) mixing said mixture to produce said decarboxylated cannabinoid formulation.
[42]
42. Method according to claim 41, characterized in that said decarboxylated cannabinoid formulation comprises at least 5 mg of decarboxylated cannabinoids.
[43]
43. Method according to claim 41, characterized in that said decarboxylated cannabinoid formulation comprises Δ ⁹ tetrahydrocannabinol.
[44]
44. Method according to claim 41, characterized by the fact that said one or more terpenoids is selected from the group consisting of: mycrene, limonene, linalool, trans
Petition 870190097797, of 9/30/2019, p. 83/284
8/9 ochine, òeta-pinene, a / fa-pinene, òefa-caríofileno, delta-3-careno, trans-gamme-bisabolene, trans-a / fa-farnesene, ôete-fenchol, ôete-fenchol, alfahumulene, and guajokul
[45]
45. Method according to claim 41, characterized in that said acid is a weak acid.
[46]
46. Method according to claim 41, characterized in that said acid has a pKa of about 3 to about 7.
[47]
47. Method according to claim 41, characterized in that said acid is selected from the group consisting of: lactic acid, citric acid, malic acid, acetic acid, benzoic acid, ascorbic acid, tartaric acid, and acid oxalic.
[48]
48. Unit dose characterized by the fact that it comprises:
(i) a mixture of carboxylated cannabinoids and decarboxylated cannabinoids, and (ii) one or more terpenoids, in which a weight / weight ratio of decarboxylated cannabinoids to carboxylated cannabinoids is greater than 0.5, in which said unit dose is substantially free of terpenoid degrading compounds, and in which said unit dose is substantially free of an acid.
[49]
49. Unit dose according to claim 48, characterized in that said acid is a weak acid.
[50]
50. Unit dose according to claim 48, characterized in that said acid has a pKa of about 3 to about 7.
[51]
51. Unit dose according to claim 48, characterized by the fact that said acid is selected from the group consisting of: lactic acid, citric acid, malic acid, acid
Petition 870190097797, of 9/30/2019, p. 84/284
9/9 acetic, benzoic acid, ascorbic acid, tartaric acid, and oxalic acid.

类似技术:

---

公开号 | 公开日 | 专利标题

---

BR112019020554A2|2020-04-28|methods and compositions to improve health conditions

---

Wu et al.2010|Vitamin E protects against oxidative damage and learning disability after mild traumatic brain injury in rats

---

Cope et al.2010|Role of zinc in the development and treatment of mood disorders

---

EP1937232B1|2011-12-21|Nutraceutical composition for the treatment of muscle wasting

---

Rock et al.2013|Effect of low doses of cannabidiolic acid and ondansetron on LiCl‐induced conditioned gaping | in rats

---

US9486464B2|2016-11-08|Composition and method of manufacture

---

EP2123266B1|2014-01-15|Cancer therapeutic agent and anti-carcinogenic agent

---

CN102014897A|2011-04-13|Compounds, compositions and methods for making the same

---

US11213559B2|2022-01-04|Formulation for treatment of irritable bowel disease

---

CN105101958A|2015-11-25|Treating pulmonary conditions

---

Jan et al.2007|Evidence supporting the use of melatonin in short gestation infants

---

JP5537151B2|2014-07-02|Tranquilizers and functional foods

---

EA026746B1|2017-05-31|Pharmaceutical composition comprising inositol

---

CN110087492A|2019-08-02|Lipid-metabolism composition for promoting containing Isoxanthohumol

---

Gentile2006|Quetiapine-fluvoxamine combination during pregnancy and while breastfeeding

---

Franco et al.2003|Vitamins C and E improve endothelial dysfunction in intrauterine-undernourished rats by decreasing vascular superoxide anion concentration

---

WO2015089656A1|2015-06-25|Compositions comprising vitamin c, vitamin e, and coenzyme q10 and use thereof for promoting female fertility and reproductive health

---

D'angelo et al.2020|Melatonin administration from 2000 to 2020 to human newborns with hypoxic-ischemic encephalopathy

---

Mindell et al.2011|Earl Mindell's New Vitamin Bible

---

CN102860984B|2014-03-26|Method for preparing compound sulfachloropyridazine sodium powder

---

WO2018222164A2|2018-12-06|Use of an herbal formula containing pumpkin seed oil in bph treatment

---

TW201821081A|2018-06-16|New composition for treating SMA

---

WO2018009664A1|2018-01-11|Stable pro-vitamin derivative compounds, pharmaceutical and dietary compositions, and methods of their use

---

WO2021206020A1|2021-10-14|Prophylactic or therapeutic agent for attention-deficit hyperactivity disorder

---

CN106974292B|2021-02-26|A vitamin composition health food comprising vitamin D, E and folic acid

同族专利:

---

公开号 | 公开日

---

GB2577810A|2020-04-08|

---

CN110709069A|2020-01-17|

---

WO2018183115A1|2018-10-04|

---

AU2018243694A1|2019-10-17|

---

CA3057994A1|2018-10-04|

---

GB201914076D0|2019-11-13|

---

IL269642D0|2019-11-28|

---

JP2020512358A|2020-04-23|

---

EP3600271A1|2020-02-05|

---

US20200101041A1|2020-04-02|

---

EP3600271A4|2020-12-16|

---

MX2019011510A|2020-01-09|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

GB2400320B|2001-05-04|2005-06-08|Gw Pharma Ltd|Cannabinoid-rich extracts|

---

CA2904968A1|2013-03-14|2014-10-02|Sc Laboratories, Inc.|Bioactive concentrates and uses thereof|

---

CA3135893A1|2014-10-21|2016-04-28|United Cannabis Corp.|Cannabis extracts and methods of preparing and using same|

---

WO2016123475A1|2015-01-31|2016-08-04|Constance Therapeutics, Inc.|Methods for preparation of cannabis oil extracts and compositions|

---

AU2016225026A1|2015-02-27|2017-09-07|Canopy Growth Corporation|Compositions comprising combinations of purified cannabinoids, with at least one flavonoid, terpene, or mineral|

---

US9747740B2|2015-03-02|2017-08-29|Ford Global Technologies, Llc|Simultaneous button press secure keypad code entry|

---

CA3022553A1|2016-05-06|2017-11-09|Zeyead GHARIB|The manufacturing methods, compositions, and medical applications of orally administered cannabis pharmaceuticals|

---

CN109843287A|2016-08-03|2019-06-04|塞尔达治疗手术有限公司|Cannabis composition|

---

US20180344786A1|2017-06-06|2018-12-06|NC3 Systems|System and method enhanced cannabiniod effect delivery|

---

EP3687511A4|2017-09-28|2021-11-24|Canopy Growth Corporation|Edible cannabinoid compositions|US10239808B1|2016-12-07|2019-03-26|Canopy Holdings, LLC|Cannabis extracts|

---

GB2571696B|2017-10-09|2020-05-27|Compass Pathways Ltd|Large scale method for the preparation of Psilocybin and formulations of Psilocybin so produced|

---

EP3745884A1|2018-01-31|2020-12-09|Canopy Holdings, Llc|Hemp powder|

---

AU2018417229A1|2018-04-04|2020-10-15|Vinsan Therapeutics Inc.|Topical cannabinoid formulations and instillates, kits, and methods for treating integumentary wounds, and uses thereof|

---

US11040932B2|2018-10-10|2021-06-22|Treehouse Biotech, Inc.|Synthesis of cannabigerol|

---

WO2020084450A1|2018-10-23|2020-04-30|Radient Technologies Innovations Inc.|Method of automating cannabis decarboxylation and extraction by recursive decarboxylation, sampling, and extraction steps|

---

WO2020084425A1|2018-10-24|2020-04-30|Radient Technologies Innovations Inc.|Side effect and symptom relief|

---

US10959961B2|2018-12-14|2021-03-30|Natural Extraction Systems, LLC|Methods of administering anionic cannabinoid molecules dissolved in water|

---

US10609944B1|2018-12-14|2020-04-07|Natural Extraction Systems, LLC|Compositions comprising 2-[-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate and 2-[-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol|

---

WO2021016710A1|2019-07-30|2021-02-04|Tassili Life Sciences, Corp.|Controlled release formulations of multiple active pharmaceutical agents, and psilocybe-derived agents in combination with cannabis-derived agents and methods for their use|

---

US10780075B1|2019-07-31|2020-09-22|Etain IP, LLC|Water soluble cannabis composition|

---

WO2021051105A2|2019-09-12|2021-03-18|Nulixir Inc.|Controlled release core-shell particles and suspensions including the same|

法律状态:
2021-10-19| B350| Update of information on the portal [chapter 15.35 patent gazette]|

优先权:

---

申请号 | 申请日 | 专利标题

---

US201762479091P| true| 2017-03-30|2017-03-30|

---

US201762506475P| true| 2017-05-15|2017-05-15|

---

US201862632965P| true| 2018-02-20|2018-02-20|

---

PCT/US2018/024061|WO2018183115A1|2017-03-30|2018-03-23|Methods and compositions for enhancing health|

---