Compositions and methods for regulating sleep and uses thereof

Abstract

Disclosed herein are compositions and methods for improving sleep health benefits by providing a composition and a carrier. Some embodiments provided include, for example, administering a therapeutically effective compound of a plant extract. In some embodiments, the plant extract is Eupatorium perfoliatum. In some embodiments, the plant extract includes costunolide. JPEG2025539362000027.jpg28170

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 508,807, filed June 16, 2023, U.S. Provisional Patent Application No. 63 / 494,995, filed April 7, 2023, and U.S. Provisional Patent Application No. 63 / 384,854, filed November 23, 2022, all of which are incorporated by reference in their entirety.

[0002] FIELD OF THE DISCLOSURE The present disclosure relates to compositions and methods for preparing same. More particularly, the present disclosure relates to compositions and methods for regulating sleep by administering a therapeutically effective amount of an oral composition and a carrier. [Background technology]

[0003] High-quality sleep is essential for good mental and physical health and quality of life. Poor sleep is associated with a variety of adverse health and social outcomes, including impaired performance at school and work. Reduced sleep duration is associated with 7 of the 15 leading causes of death in the United States, including cardiovascular disease, malignant neoplasms, cerebrovascular disease, accidents, diabetes, sepsis, and hypertension.

[0004] Given the current epidemic of chronic diseases related to sleep deprivation afflicting the world's population, inventions that improve or mitigate the negative effects of sleep deprivation would have immediate and immeasurable benefits to the health of people worldwide. Good sleep hygiene, which includes maintaining consistent bedtimes and wake times, reducing caffeine intake, and managing screen time before bed, can promote optimal sleep duration and quality.

[0005] Therapeutic intervention is the most common treatment for sleep disorders. Currently, three molecules, suvorexant, lemborexant, and daridrexant, are FDA-approved for the treatment of insomnia via orexin receptor antagonism. Several molecules are being investigated for insomnia. However, most therapeutic agents are not suitable for routine consumption as nutritional interventions.

[0006] A variety of herbal remedies and dietary supplements are advertised as sleep aids. These include melatonin, valerian root, German centipede, kava, L-tryptophan, small-leaf linden (Tilia), verbena (verbena), monk balm (Melissa), and skullcap (Scutellaria). However, these products are not consistently regulated, resulting in variable purity and potency of their ingredients. Scientific evidence supporting the effectiveness of these herbal remedies is limited. Most are generally considered safe, although information regarding their interactions with prescription medications is lacking. Of these, melatonin is best known for treating insomnia. Taking 3–5 mg a few hours before bedtime is typically most effective, especially when used occasionally. However, it is not recommended for the long-term management of chronic insomnia. The long-term safety of melatonin is unknown.

[0007] Clearly, there remains an unmet need to develop nutritional interventions to improve sleep quality and duration. Summary of the Invention [Problem to be solved by the invention]

[0008] Aspects of the present disclosure relate to oral compositions for improving, restoring, regulating, or maintaining sleep. In some embodiments, the oral compositions include a therapeutically effective amount of a botanical extract and one or more carriers or excipients, wherein the botanical extract is capable of improving, restoring, regulating, or maintaining sleep. In some embodiments, the botanical extract is Eupatorium perfoliatum, Zingiber officinale, Picea sitchensis, Viburnum davidii, Arnica montana, Helianthus annuus, Lactuca sativa, Barnadesia spinosa, Dolomiaea souliei, Saussurea costus, Artemisia annua, Inula helenium, Laurus nobilis, Momodica cochinchinensis, Pogostemon cablin, Tanacetum parthenium, Cichorium intybus, Solidago Canadensis, Horeum vulgare, Tricum aestivum, Silene conica, Alloteropsis semialata, Paris polyphylla, Camella sinensis, Glebionis cornaria, Hordeum vulgare, Setaria italic, Zea mays, Arabidopsis thaliana, Brachypodium distachyon, Grindelia integrifolia, Lobelia chinesis, Arachis hypogaea, Nepenthes khasiana, Selaginella mollendorffii, Taxus x media, Acorus gramieus, Andrographis paniculata, Artemisia maritima, Bletilla striata, Fallopia multflora, Gossypium hirsutum, Hordeum spontaneum, Hypericum perforatum, Musa acuminate, Oryza rufipogon, Oryza sativa,In some embodiments, the plant extract is selected from the group consisting of Quercus suber, Solanum tuberosum, Valeriana officinalis, Vitis vinifera, Polygonatum odoratum, Glycine max, Panicum virgatum cv. Trailblazer, or Populus trichorarpa. In some embodiments, the plant extract is selected from the group consisting of costunolide, 5a,9-dimethyl-3-methylidene-3ah,4h,5h,9bh-naphtho[1,2-b]furan-2,8-dione, bainol A, (3r,3ar,4r,11as)-3,6,10-trimethyl-2-oxo-3h,3ah,4h,7h,8h,11h,11ah-cyclodeca[b]furan-4-ylacetone, (3r,3as, 4r,11aS)-4-Hydroxy-3,6,10-trimethyl-3h,3ah,4h,7h,8h,11h,11ah-cyclodeca[b]furan-2-one, 1R,2S,5S,6S,7S)-5-isopropyl-2,8-dimethyltricyclo[4.4.0.02,7]dec-8-en-4-one, 2-((1R,3S,4R)-4-methyl-3-(prop-1en-2-yl)-4-vinylsilyl) cyclohexyl)acrylaldehyde, 3,7,11-trimethyldodeca-1,3,5,8,10-pentaene, p-cymene, (1S,2R,4R,7E,11S)-4,8-dimethyl-12-methylidene-3,14-dioxatricyclo[9.3.0.02,4]tetradec-7-en-13-one, 3-[(3aS,4R,5R,8aR)-4-hydroxy-5,7-dimethyl-3-methylidene -2-oxo-4,5,8,8a-tetrahydro-3aH-cyclohepta[b]furan-6-yl]propylacetone, 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxychromen-4-one, 5,7-dihydroxy-2-(4-hydroxyphenyl)-3,6-dimethoxychromen-4-one,2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxymethyl]oxan-2-yl]oxychromen-4-one, 1-(2-hydroxy-4-methoxyphenyl)-3-(4-hydroxyphenyl)propan-1-one, 3-(4-hydroxyphenyl)-1-[4-hydroxy-2-[3,4,5-trihydroxy-6-( 3-(4-hydroxyphenyl)-1-[4-methoxy-2-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]propan-1-one, 3-(4-hydroxyphenyl)-1-[2-hydroxy-4-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]propan-1-one, (2S,3S,4S,5R,6S)-6-[5,7-dihydroxy-2-(4- hydroxyphenyl)-4-oxochromen-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid, 7-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, 3-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydrox- 3-[(2S,5R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2S,3S,5R)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, 3-[(2S,5R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2S,3S,5R)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one,[(2R,3S,4S,5R,6S)-6-[3,5-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-8-methoxy-4-oxochromen-7-yl]oxy-3,4-dihydroxy-5-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]methylacetone, 5,7-dihydroxy-2-(4-hydroxyphenyl)-3-[(2S,3R,4S,5S)-3,4,5-trihydroxyoxan-2-yl] yl]oxychromen-4-one, 3-[(2S,3R,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, (2S,3S,4S,5R,6S)-6-[4-(5,7-dihydroxy-3,6-dimethoxy-4-oxochromen-2-yl)-2-hydroxyphenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid, 2-(3,4-dihydroxyphenyl)-3,5 ,7-trihydroxychromen-4-one, 1,6-dihydroxy-3-methyl-8-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyanthracene-9,10-dione, 1,3,8-trihydroxy-6-methylanthracene-9,10-dione, (E)-3-(4-hydroxyphenyl)-N-[4-[[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]-[3-[[(E)-3-(4-hydroxyphenyl) 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-6-methoxychromen-4-one,The oral composition comprises a compound selected from the group consisting of (E)-3-(4-hydroxyphenyl)-N-[3-[[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]-[4-[[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]-[3-[[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]amino]propyl]amino]butyl]amino]propyl]prop-2-enamide, (1S,3R,4R,5R)-3,4-bis[[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy]-1,5-dihydroxycyclohexane-1-carboxylic acid, and 5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one. In some embodiments, the oral composition is formulated as a dietary supplement, a food ingredient or additive, a medical food, a nutraceutical, or a pharmaceutical composition. In some embodiments, the oral composition is in a dosage form configured as one of a soft gel capsule, a hard capsule, a liquid, a powder, and a tablet. In some embodiments, the oral composition comprises 10%-99% w / w of a plant extract. In some embodiments, the excipient further comprises a preservative. In some embodiments, the plant extract further comprises a sweetener. In some embodiments, the plant extract further comprises a colorant. In some embodiments, the plant extract further comprises an additive. In some embodiments, the plant extract further comprises a flavoring agent.

[0009] Some aspects of the present disclosure relate to methods of improving, restoring, regulating, or maintaining sleep in a subject in need thereof. In some embodiments, the method comprises administering a therapeutically effective amount of an oral composition described herein. Some aspects of the present disclosure relate to methods of treating a sleep disorder in a subject in need thereof. In some embodiments, the method comprises administering a therapeutically effective amount of an oral composition described herein. In some embodiments, the plant extract comprises an orexin receptor 2 antagonist. In some embodiments, the plant extract comprises an orexin receptor 1 antagonist. In some embodiments, the plant extract further results in decreased calcium influx. In some embodiments, the plant extract further results in decreased phosphorylation of pERK1 / 2. In some embodiments, improving sleep results in the subject getting a full night's sleep. In some embodiments, improving sleep results in the subject getting a restful night's sleep. In some embodiments, regulating sleep results in an increase in slow wave sleep 1-4 in the subject. In some embodiments, regulating sleep results in an increase in REM sleep in the subject. In some embodiments, the sleep disorder is selected from the group consisting of insomnia, sleep-related breathing disorders, central hypersomnia, circadian rhythm sleep-wake disorders, parasomnia, and sleep-related movement disorders. In some embodiments, the sleep disorder is selected from the group consisting of insomnia, narcolepsy, hypersomnia, sleep apnea, periodic limb movement disorder, restless legs syndrome, nocturnal eating syndrome, jet lag, shift work sleep disorder, irregular sleep-wake patterns, confusional awakenings, sleepwalking, sleep terrors, sleep talking, nightmares, sleep paralysis, REM sleep behavior disorder, snoring, and sleeping sickness.

[0010] Features and advantages of the compositions and methods described herein will become apparent from the following description considered in conjunction with the accompanying drawings. These drawings depict certain aspects of the compositions and methods described in this application and, therefore, should not be considered limiting. In the drawings, like reference numbers or symbols typically identify like components unless the context dictates otherwise. The drawings may not be drawn to scale. [Brief explanation of the drawings]

[0011] [Figure 1] 1 is a graph showing the in vitro biological activity of Compound 20 on orexin receptor 2. [Figure 2] 1 is a graph showing the in vitro biological activity of compound 21 on orexin receptor 2. [Figure 3] 1 is a graph showing the in vitro biological activity of Compound 22 on orexin receptor 2. [Figure 4] 1 is a graph showing the in vitro biological activity of Compound 23 on orexin receptor 2. [Figure 5] 1 is a graph showing the in vitro biological activity of Compound 24 on orexin receptor 2. [Figure 6] 1 is a graph showing the in vitro biological activity of Compound 25 on orexin receptor 2. [Figure 7] 1 is a graph showing the in vitro biological activity of Compound 26 on orexin receptor 2. [Figure 8] 1 is a graph showing the in vitro biological activity of Compound 27 on orexin receptor 2. [Figure 9] 1 is a graph showing the in vitro biological activity of Compound 28 on orexin receptor 2. [Figure 10] 1 is a graph showing the in vitro biological activity of Compound 29 on orexin receptor 2. [Figure 11] 1 is a graph showing the in vitro biological activity of Compound 30 on orexin receptor 2. [Figure 12] 1 is a graph showing the in vitro biological activities of compounds 31 to 38 on orexin receptors (Orx1 and Orx2). DETAILED DESCRIPTION OF THE INVENTION

[0012] The present disclosure provides, among other things, the discovery of compounds, compositions, and methods for improving, restoring, regulating, or maintaining sleep in a subject. In aspects, the compositions include one or more compounds described herein and a carrier. In some aspects, the methods include orally administering one or more compounds described herein or compositions described herein, thereby improving, restoring, regulating, or maintaining sleep in a subject. In some embodiments, the oral compositions may further improve a person's sleep quality, for example, by promoting the maintenance of sleep conducive to restful sleep. The oral compositions described herein employed in various embodiments of the present disclosure have been shown to be antagonists of specific receptors that may be involved in the induction and regulation of sleep.

[0013] Additionally, the oral compositions disclosed herein may also be useful in modulating satiety or disorders related to satiety.

[0014] definition Unless expressly defined otherwise, technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In the event that there are multiple definitions of terms herein, the definition in this section prevails unless expressly stated otherwise. As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Unless otherwise stated, the use of either the conjunction "or" or "and" means "and / or." Furthermore, the use of the term "including," as well as other forms such as "include," "includes," and "included," is not limiting. As used herein, whether in transitional phrases or in the body of the claims, the terms "comprise(s)" and "comprising" should be construed as having an open-ended meaning. That is, these terms should be construed synonymously with the phrases "having at least" or "including at least." When used in the context of a process, the term "comprising" means that the process includes at least the recited steps, but may include additional steps. When used in the context of a compound, composition, or device, the term "comprising" means that the compound, composition, or device includes at least the recited features or components, but may also include additional features or components.

[0015] When a range of values ​​is provided, it is understood that the upper and lower limits, and every intervening value between the upper and lower limits of the range, are encompassed within the embodiments.

[0016] While the present disclosure has been illustrated and described in detail in the foregoing description, such description is intended to be illustrative or exemplary and not restrictive. The present disclosure is not limited to the disclosed embodiments. Variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed disclosure, from a study of this disclosure and the appended claims.

[0017] All references mentioned herein are incorporated herein by reference in their entirety. To the extent that publications and patents or patent applications incorporated by reference conflict with the disclosure contained herein, the present specification supersedes and / or is intended to take precedence over such conflicting material.

[0018] Compounds disclosed herein having at least one chiral center may exist as racemates or individual enantiomers, or as enantiomerically enriched mixtures of enantiomers. It should be noted that all such isomers and mixtures thereof are within the scope of the present invention. Furthermore, crystalline forms of compounds disclosed herein may exist as different polymorphs. Such polymorphs are included in one embodiment of the present invention. In addition, some of the compounds of the present invention may form solvates with water (i.e., hydrates) or common organic solvents. Such solvates are included in one embodiment of the present invention.

[0019] As used herein, the term "pharmaceutically acceptable salt" refers to a salt of a compound that does not cause significant irritation to an organism to which it is administered and does not abrogate the biological activity and properties of the compound. In some embodiments, the salt is an acid addition salt of the compound. Pharmaceutical salts can be obtained by reacting a compound with an inorganic acid such as a hydrohalic acid (e.g., hydrochloric acid, hydrobromic acid), sulfuric acid, nitric acid, phosphoric acid, etc. Pharmaceutical salts can also be obtained by reacting a compound with an organic acid such as an aliphatic or aromatic carboxylic or sulfonic acid, for example, acetic acid, succinic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, nicotinic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, or naphthalenesulfonic acid. Pharmaceutical salts can also be obtained by reacting a compound with a base to form an ammonium salt; an alkali metal salt such as a sodium salt or a potassium salt; an alkaline earth metal salt such as a calcium salt or a magnesium salt; a salt of an organic base such as dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, C1-C7 alkylamine, cyclohexylamine, triethanolamine, ethylenediamine, etc.; a salt with an amino acid such as arginine or lysine, etc.

[0020] As used herein, the term "pharmaceutically acceptable carrier" or "pharmaceutically acceptable excipient" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in therapeutic compositions is contemplated. In addition, various adjuvants commonly used in the art may be included. Considerations for including various ingredients in pharmaceutical compositions are described, for example, in Gilman et al. (Eds.) (1990); Goodman and Gilman's: The Pharmacological Basis of Therapeutics, 8th Ed., Pergamon Press, the entire contents of which are incorporated herein by reference.

[0021] The term "halogen," as used herein, means any one of the radiostable atoms in column 7 of the periodic table of the elements, for example, fluorine, chlorine, bromine, or iodine.

[0022] Any amine, hydroxyl, or carboxyl side chain on the compounds disclosed herein can be esterified or amidated. The procedures and specific groups used to achieve this purpose are known to those of skill in the art and can be readily found in references such as Greene and Wuts, Protective Groups in Organic Synthesis, 3rd Ed. John Wiley & Sons, New York, NY, 1999, which is incorporated herein in its entirety.

[0023] As used herein, "C" is a set of integers where "a" and "b" are integers. a From C b " or "C a ~C b" refers to the number of carbon atoms in an alkyl, alkenyl, or alkynyl group, or the number of carbon atoms in a cycloalkyl, aryl, heteroaryl, or heterocyclyl ring. That is, the alkyl, alkenyl, alkynyl, cycloalkyl ring, aryl ring, heteroaryl ring, or heterocyclyl ring can contain from "a" to "b" carbon atoms. Thus, for example, a "C1 to C4 alkyl" group or a "C1-C4 alkyl" group refers to all alkyl groups having 1 to 4 carbons, i.e., CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)-, and (CH3)3C-. Similarly, for example, a cycloalkyl group may contain "a" through "b" total atoms, including 3 to 8 carbon atoms in the ring(s), such as a C3-C8 cycloalkyl group. When "a" and "b" are not specified with respect to alkyl, cycloalkyl, or cycloalkenyl, the broadest range described by those definitions is assumed. Similarly, a "4- to 7-membered heterocyclyl" group refers to all heterocyclyl groups having a total of 4 to 7 ring atoms, such as azetidine, oxetane, oxazoline, pyrrolidine, piperidine, piperazine, morpholine, and the like. As used herein, the term "C1-C6" includes C1, C2, C3, C4, C5, and C6, as well as ranges defined by either of the two preceding numbers. For example, C1-C6 alkyl includes C1, C2, C3, C4, C5, and C6 alkyl, C2-C6 alkyl, C1-C3 alkyl, and the like. Similarly, C3-C8 carbocyclyl or cycloalkyl includes hydrocarbon rings containing 3, 4, 5, 6, 7, and 8 carbon atoms, respectively, or ranges defined by either of the two numbers, such as C3-C7 cycloalkyl or C5-C6 cycloalkyl. As another example, a 3- to 10-membered heterocyclyl includes 3, 4, 5, 6, 7, 8, 9, or 10 ring atoms, or a range defined by either of the previous two numbers, such as a 4- to 6-membered or 5- to 7-membered heterocyclyl.

[0024] As used herein, "alkyl" refers to a hydrocarbon group that is straight or branched, fully saturated (no double or triple bonds), or a hydrocarbon chain. The alkyl group may have 1 to 20 carbon atoms. (Whenever it appears herein, a numerical range such as "1 to 20" refers to each integer within the given range; for example, "1 to 20 carbon atoms" means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc. (up to 20 carbon atoms), but this definition also encompasses the occurrence of the term "alkyl" without a specified numerical range.) The alkyl group may also be a medium-sized alkyl having 1 to 10 carbon atoms. The alkyl group may also be a lower alkyl having 1 to 5 carbon atoms. The alkyl group of a compound may be designated as "C1-C4 alkyl" or similar designation. As an example, "C1-C4 alkyl" indicates that there are 1 to 4 carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and t-butyl. Typical alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, ethenyl, propenyl, butenyl, and the like.

[0025] An alkyl group can be substituted or unsubstituted. If substituted, the substituent(s) can be alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, protected hydroxyl, alkoxy, aryloxy, acyl, ester, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl. and one or more group(s) individually and independently selected from: C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, protected C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino (including mono- and di-substituted amino groups), and protected derivatives thereof. Whenever a substituent is described as "optionally substituted," that substituent may be substituted with one of the above substituents.

[0026] As used herein, "cycloalkyl" refers to a monocyclic or polycyclic hydrocarbon ring system that is fully saturated (no double bonds). When composed of two or more rings, the rings may be fused, bridged, or spiro-connected. Cycloalkyl groups include C3 to C6. 10 and in other embodiments, from C3 to C6. The cycloalkyl group can be unsubstituted or substituted. Typical cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. When substituted, the substituent(s) can be alkyl or selected from those described above for alkyl group substitution, unless otherwise specified. When substituted, the substituents on the cycloalkyl group can form an aromatic ring fused to the cycloalkyl group, including aryl and heteroaryl.

[0027] As used herein, "heteroalkyl" refers to a straight or branched hydrocarbon chain containing one or more heteroatoms, i.e., elements other than carbon, including, but not limited to, nitrogen, oxygen, and sulfur, in the chain backbone. Heteroalkyl groups can have from 1 to 20 carbon atoms, although this definition also encompasses the occurrence of the term "heteroalkyl" where no numerical range is specified. Heteroalkyl groups can also be medium-sized heteroalkyls having from 1 to 9 carbon atoms. Heteroalkyl groups can also be lower heteroalkyls having from 1 to 4 carbon atoms. The heteroalkyl group of a compound can be defined as "C 1~4 A heteroalkyl group may be designated "heteroalkyl" or similar designations. A heteroalkyl group may contain one or more heteroatoms. By way of example only, "C 1~4 "Heteroalkyl" indicates that there are from 1 to 4 carbon atoms in the heteroalkyl chain and that there is one or more heteroatoms in the backbone of the chain.

[0028] As used herein, the term "amino" refers to R A and R B is, as defined herein, hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~7 Carbocyclyl, C 6~10 "-NR" is independently selected from aryl, 5- to 10-membered heteroaryl, and 5- to 10-membered heterocyclyl; A R B " refers to the group.

[0029] As used herein, "aryl" refers to a carbocyclic (all carbon) ring or two or more fused rings (rings sharing two adjacent carbon atoms) having a completely delocalized π-electron system. Examples of aryl groups include, but are not limited to, benzene, naphthalene, and azulene. An aryl group may be substituted or unsubstituted. When substituted, a hydrogen atom may be substituted with an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, protected hydroxyl, alkoxy, aryloxy, acyl, ester, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, Substituted with substituent(s) that are one or more group(s) independently selected from C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, protected C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and protected derivatives thereof. When substituted, the substituents on the aryl group may form a non-aromatic ring fused to the aryl group, including cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclyl.

[0030] As used herein, "heteroaryl" refers to a monocyclic or polycyclic aromatic ring system (a ring system having a fully delocalized π-electron system), one or more fused rings containing one or more heteroatoms, i.e., elements other than carbon, including, but not limited to, nitrogen, oxygen, and sulfur. Examples of heteroaryl rings include, but are not limited to, furan, thiophene, phthalazine, pyrrole, oxazole, thiazole, imidazole, pyrazole, isoxazole, isothiazole, triazole, thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine, and triazine. Heteroaryl groups can be substituted or unsubstituted. When substituted, a hydrogen atom may be substituted with alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, protected hydroxyl, alkoxy, aryloxy, acyl, ester, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, Substituted with substituent(s) that are one or more group(s) independently selected from C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, protected C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and protected derivatives thereof. When substituted, substituents on a heteroaryl group may form a non-aromatic ring fused to the aryl group, including cycloalkyl, cycloalkenyl, cycloalkynyl, and heterocyclyl.

[0031] As used herein, "heterocyclyl" refers to a non-aromatic cyclic ring or ring system containing at least one heteroatom in the ring backbone. Heterocyclyls may be linked together in fused, bridged, or spiro-linked forms. Heterocyclyls may be saturated to any degree, provided that at least one ring in the ring system is not aromatic. The heteroatom(s) may be present in either the non-aromatic or aromatic ring of the ring system. Heterocyclyl groups may have 3 to 20 ring members (i.e., the number of atoms comprising the ring backbone, including carbon atoms and heteroatoms), although this definition also covers occurrences of the term "heterocyclyl" where no numerical range is specified. Heterocyclyl groups may also be medium-sized heterocyclyls having 3 to 10 ring members. Heterocyclyl groups may also be heterocyclyls having 3 to 6 ring members. Heterocyclyl groups may also be designated as "3 to 6-membered heterocyclyl" or similar designations. In preferred 6-membered monocyclic heterocyclyls, the heteroatom(s) are selected from 1 to 3 of O, N or S, and in preferred 5-membered monocyclic heterocyclyls, the heteroatom(s) are selected from 1 or 2 heteroatoms selected from O, N or S.Examples of heterocyclyl rings include azepinyl, acridinyl, carbazolyl, cinnolinyl, dioxolanyl, imidazolinyl, imidazolidinyl, morpholinyl, oxiranyl, oxepanyl, thiepanyl, piperidinyl, piperazinyl dioxopiperazinyl, pyrrolidinyl, pyrrolidonyl, pyrrolidionyl, 4-piperidonyl, pyrazolinyl, pyrazolidinyl, 1,3-dioxinyl, 1,3-dioxanyl, 1,4-dioxinyl, 1,4-dioxanyl, 1,3-oxathianiyl, 1,4-oxathianiyl, 2H-1,2-oxazinyl, trioxanyl, hexahydro-1,3,5-triazinyl, 1,3-dioxolyl, 1,3-dioxolanyl, 1,3-dithiol, 1,3-dithiolanyl, isoxa These include, but are not limited to, oxolinyl, isoxazolidinyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, thiazolinyl, thiazolidinyl, 1,3-oxathiolanyl, indolinyl, isoindolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, tetrahydro-1,4-thiazinyl, thiamorpholinyl, dihydrobenzofuranyl, benzimidazolidinyl, and tetrahydroquinoline.

[0032] As used herein, the terms "purified," "substantially purified," and "isolated" refer to the compounds disclosed herein being free of other heterogeneous compounds with which the compounds of the invention are normally associated in nature, such that the compounds of the invention comprise at least 0.5%, 1%, 5%, 10%, or 20%, and most preferably at least 50% or 75%, by weight of the mass of a given sample.

[0033] A substituent is based on or derived from an unsubstituted parent group in which one or more hydrogen atoms have been replaced with another atom or group. Unless otherwise specified, when a group is deemed to be "substituted" or "optionally substituted," that group includes C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C3-C7 carbocyclyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), C3-C7-carbocyclyl-C1-C6 alkyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy). 5-10 membered heterocyclyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 membered heterocyclyl-C1-C6-alkyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), aryl (halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), aryl(C1-C6)alkyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 membered heteroaryl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 membered heteroaryl(C1-C6)alkyl (halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), optionally substituted with alkoxy), halo, cyano, hydroxy, C1-C6 alkoxy, C1-C6 alkoxy(C1-C6)alkyl (i.e., ether), aryloxy, sulfhydryl (mercapto), halo(C1-C6)alkyl (e.g., -CF3), halo(C1-C6)alkoxy (e.g., -OCF3), C1-C6 alkylthio, arylthio, amino, amino(C1-C6)alkyl, nitro, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido,Substituted with one or more substituents independently selected from S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, acyl, cyanato, isocyanato, thiocyanato, isothiocyanato, sulfinyl, sulfonyl, and oxo (=O). Whenever a group is described as "optionally substituted," that substituent can be substituted with the above substituents.

[0034] As used herein, the term "subject" refers to a human or non-human mammal, e.g., a dog, cat, mouse, rat, cow, sheep, pig, goat, non-human primate, or bird, e.g., a chicken, as well as any other vertebrate or invertebrate.

[0035] It is to be understood that if the compounds disclosed herein have unsatisfied valences, the valences should be filled with hydrogen and / or deuterium.

[0036] The term "about" as used herein refers to an amount, level, value, number, frequency, percentage, dimension, size, amount, weight, or length that varies by as much as 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1% relative to a reference amount, level, value, number, frequency, percentage, dimension, size, amount, weight, or length. When the term about precedes a value, it is not intended that the element be strictly limited to that value, but rather that amounts different from the value are included.

[0037] compound In some aspects, the disclosure provides compounds of formula (I): [ka]

[0038] In some embodiments, Formula (I) is a salt described herein. In some embodiments, the salt is suitable for oral ingestion. In some embodiments, the salt is a pharmaceutically acceptable salt.

[0039] In some embodiments, formula (I) is represented by formula (IA): [ka]

[0040] In some embodiments, formula (I) is represented by formula (IB): [ka]

[0041] In some aspects, the disclosure provides compounds of formula (II): [ka]

[0042] In some embodiments, Formula (II) is a salt as described herein. In some embodiments, the salt is suitable for oral ingestion. In some embodiments, the salt is a pharmaceutically acceptable salt.

[0043] In some aspects, the disclosure provides compounds of formula (III): [ka]

[0044] In some embodiments, Formula (III) is a salt as described herein. In some embodiments, the salt is suitable for oral ingestion. In some embodiments, the salt is a pharmaceutically acceptable salt.

[0045] In some embodiments of compounds of Formula (I), (IA), (IB), (II), or (III), R 1is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted -C1-C6 alkyl, optionally substituted -O-C1-C6 alkyl, optionally substituted -C3-C8 cycloalkyl, optionally substituted -O-C3-C8 cycloalkyl, optionally substituted -C3-C8 heteroalkyl, optionally substituted -O-C3-C8 heteroalkyl, optionally substituted -C6-C 10 Aryl, optionally substituted -O-C-C 10 aryl, or L.

[0046] In some embodiments of compounds of Formula (I), (IA), (II), or (III), R 2 is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted -C1-C6 alkyl, optionally substituted -O-C1-C6 alkyl, optionally substituted -C3-C8 cycloalkyl, optionally substituted -O-C3-C8 cycloalkyl, optionally substituted -C3-C8 heteroalkyl, optionally substituted -O-C3-C8 heteroalkyl, optionally substituted -C6-C 10 Aryl, optionally substituted -O-C6-C 10 aryl, or L.

[0047] In some embodiments of compounds of Formula (I), (IB), (II), or (III), R 3 is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted -C1-C6 alkyl, optionally substituted -O-C1-C6 alkyl, optionally substituted -C3-C8 cycloalkyl, optionally substituted -O-C3-C8 cycloalkyl, optionally substituted -C3-C8 heteroalkyl, optionally substituted -O-C3-C8 heteroalkyl, optionally substituted -C6-C 10 Aryl, optionally substituted -O-C-C 10 aryl, or L.

[0048] In some embodiments of compounds of Formula (I) or (IA), R 4is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted -C1-C6 alkyl, optionally substituted -O-C1-C6 alkyl, optionally substituted -C3-C8 cycloalkyl, optionally substituted -O-C3-C8 cycloalkyl, optionally substituted -C3-C8 heteroalkyl, optionally substituted -O-C3-C8 heteroalkyl, optionally substituted -C6-C 10 Aryl, optionally substituted -O-C6-C 10 aryl, or L.

[0049] In some embodiments of compounds of Formula (I) or (IB), R 5 is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted -C1-C6 alkyl, optionally substituted -O-C1-C6 alkyl, optionally substituted -C3-C8 cycloalkyl, optionally substituted -O-C3-C8 cycloalkyl, optionally substituted -C3-C8 heteroalkyl, optionally substituted -O-C3-C8 heteroalkyl, optionally substituted -C6-C 10 Aryl, optionally substituted -O-C6-C 10 aryl, or L.

[0050] In some embodiments of compounds of Formula (I) or (IB), R 6 is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted -C1-C6 alkyl, optionally substituted -O-C1-C6 alkyl, optionally substituted -C3-C8 cycloalkyl, optionally substituted -O-C3-C8 cycloalkyl, optionally substituted -C3-C8 heteroalkyl, optionally substituted -O-C3-C8 heteroalkyl, optionally substituted -C6-C 10 Aryl, optionally substituted -O-C6-C 10 aryl, or L.

[0051] In some embodiments of the compounds of Formula (I), R 7is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted -C1-C6 alkyl, optionally substituted -O-C1-C6 alkyl, optionally substituted -C3-C8 cycloalkyl, optionally substituted -O-C3-C8 cycloalkyl, optionally substituted -C3-C8 heteroalkyl, optionally substituted -O-C3-C8 heteroalkyl, optionally substituted -C6-C 10 Aryl, optionally substituted -O-C6-C 10 aryl, or L.

[0052] In some embodiments of compounds of Formula (I), (IA), (IB), (II), or (III), L is -Z 1 -Z 2 In some embodiments of compounds of Formula (I), (IA), (IB), (II), or (III), L is -Z 1 -Z 2 -Z 3 In some embodiments, L is a monosaccharide. In some embodiments, L is a polysaccharide. In some embodiments of a compound of Formula (I), (IA), (IB), (II), or (III), R 1 ~R 7 At least one of is L. In some embodiments of compounds of Formula (I), (IA), (IB), (II), or (III), R 1 ~R 7 At least one of is L, and L is -Z 1 -Z 2 In some embodiments of compounds of Formula (I), (IA), (IB), (II), or (III), R 1 ~R 7 Only one of the is L and L is -Z 1 -Z 2 In some embodiments of compounds of Formula (I), (IA), (IB), (II), or (III), R 1 ~R 7 and wherein only one of is optionally substituted C3-C8 heterocyclyl.

[0053] In some embodiments of the compound of Formula (I), (IA), or (II), Z is -CH-, -O-, -NH-, optionally substituted C-C cycloalkyl, optionally substituted C-C 10 aryl, optionally substituted -C3-C8 heterocyclyl, or optionally substituted C3-C 10 In some embodiments, Z1 is optionally substituted -C3-C8 heterocyclyl.

[0054] In some embodiments of compounds of Formula (I), (IA), (IB), (II), or (III), Z 2 is hydrogen, deuterium, halo, -CH2-, -O-, -CO2H, -CO2CHCH-, optionally substituted -C3-C8 cycloalkyl, optionally substituted -C6-C 10 aryl, optionally substituted -C3-C8 heterocyclyl, or optionally substituted -C3-C 10 In some embodiments, Z is heteroaryl. 2 is an optionally substituted -C3-C8 heterocyclyl.

[0055] In some embodiments of compounds of Formula (I), (IA), (IB), (II), or (III), Z 3 is hydrogen, deuterium, halo, -CH2-, -O-, optionally substituted -C3-C8 cycloalkyl, optionally substituted -C6-C 10 aryl, optionally substituted -C3-C8 heterocyclyl, or optionally substituted -C3-C 10 In some embodiments, Z is heteroaryl. 2 is an optionally substituted -C3-C8 heterocyclyl.

[0056] In some embodiments, optionally substituted -C3-C8 heterocyclyl is [ka] In some embodiments, the optionally substituted -C3-C8 heterocyclyl is a monosaccharide. In some embodiments, the optionally substituted -C3-C8 heterocyclyl is selected from the group consisting of glucose, mannose, fructose, xylose, and rhamnose. In some embodiments, the optionally substituted -C3-C8 heterocyclyl is an enantiomer and may be D-glucose. In some embodiments, the optionally substituted -C3-C8 heterocyclyl is [ka] In some embodiments, the optionally substituted -C3-C8 heterocyclyl is [ka] In some embodiments, the optionally substituted -C3-C8 heterocyclyl is [ka] For example, in some embodiments, a compound according to Formula (I), (IA), (IB), (II), or (III) may be a structurally similar compound compared to a naturally occurring source, but may not, for example, be a naturally occurring compound. In some embodiments, a compound according to Formula (I), (IA), (IB), (II), or (III) may be chemically modified from a naturally occurring compound. For example, a compound according to Formula (I), (IA), (IB), (II), or (III) may be deuterated at one or more positions to replace a hydrogen and is not itself a naturally occurring compound.

[0057] In some embodiments of a compound of Formula (I), (IA), (IB), (II), or (III), the compound is selected from the compounds of Table A, a salt thereof, or a pharmaceutically acceptable salt thereof. Table A depicts compounds according to the present disclosure and may include isomers and stereoisomers of the depicted compounds. For example, compounds of Table A include compounds having a crossed double bond: [ka] Cis and trans isomers may be indicated by the symbol [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6]

[0058] In some embodiments, compounds of Formula (I) do not include compounds 12, 13, 14, 15, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 33, 34, 35, 38, or a combination thereof. In some embodiments, compounds of Formula (II) do not include compounds 16, 17, 18, 19, or a combination thereof. In some embodiments, compounds of Formula (III) do not include compounds 30, 31, or a combination thereof.

[0059] In some embodiments, the disclosed chemical structures may contain glucosides or other structures in which the sugar moiety is selected from the non-limiting examples of glucose, fructose, galactose, mannose, xylose, rhamnose, sialic acid, and sugar derivatives. While the metabolic products of such structures vary depending on the specific sugar / glucoside, the primary metabolic reaction of glucosides is hydrolysis. This process involves cleavage of the glycosidic bond between the glucose unit and the aglycone (the non-sugar portion of the molecule). Enzymes called glucosidases, present in various organisms, facilitate this reaction. Hydrolysis yields the sugar component (glucose) and the aglycone. Thus, the present disclosure provides aglycones for any of the disclosed compounds listed in Table A. In some embodiments, the present disclosure provides substituted flavonoids, substituted flavanones, substituted flavones, substituted chalcones, and substituted anthraquinones. In some embodiments, the flavonoid core molecule may be generated from chalcone by isomerization with the enzyme chalcone isomerase (CHI) to generate the flavanone group.

[0060] Salts of the compounds of the present disclosure refer to compounds that possess the desired pharmacological activity of the parent compound, including, but not limited to, (1) acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or salts formed with acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanoic acid, benzo ... or (2) salts formed by substitution of an acidic proton present in the parent compound.

[0061] In compounds described herein having one or more chiral centers, where the absolute stereochemistry is not specified, it is understood that each center may independently be in the R-configuration or the S-configuration, or a mixture thereof. Accordingly, the compounds provided herein may be enantiomerically pure, enantiomerically enriched, or stereoisomeric mixtures, including all diastereomeric and enantiomeric forms. Furthermore, in any compound described herein having one or more double bond(s) that produce a geometric isomer that can be defined as E or Z, it is understood that each double bond may independently be E or Z, or a mixture thereof. Stereoisomers may be obtained, if desired, by methods such as stereoselective synthesis and / or separation of stereoisomers by chiral chromatographic columns. Similarly, it is understood that all tautomeric forms are intended to be included in the described compounds.

[0062] It is understood that the compounds described herein can be isotopically labeled or labeled by other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels. Substitution with isotopes such as deuterium may provide certain therapeutic benefits resulting from greater metabolic stability, such as increased in vivo half-life or reduced dosage requirements. Each chemical element represented in a compound structure can include any isotope of that element. For example, in a compound structure, a hydrogen atom may be explicitly disclosed or understood to be present in the compound. At any position in a compound where a hydrogen atom can be present, the hydrogen atom may be any isotope of hydrogen, including, but not limited to, hydrogen 1 (protium), hydrogen 2 (deuterium), and hydrogen 3 (tritium). Therefore, reference to a compound herein encompasses all possible isotopic forms unless the context clearly indicates otherwise.

[0063] It is understood that the compounds described herein may be labeled by other means, including, but not limited to, the use of chromophores or fluorophores, bioluminescent labels, or chemiluminescent labels. Substitution with isotopes such as deuterium may provide certain therapeutic benefits resulting from greater metabolic stability, such as increased in vivo half-life or reduced dosage requirements. Each chemical element represented in a compound structure may include any isotope of that element. For example, in a compound structure, a hydrogen atom may be explicitly disclosed or understood to be present in the compound. At any position in a compound where a hydrogen atom may be present, the hydrogen atom may be any isotope of hydrogen, including, but not limited to, hydrogen 1 (protium), hydrogen 2 (deuterium), and hydrogen 3 (tritium). Therefore, reference to a compound herein encompasses all possible isotopic forms unless the context clearly indicates otherwise.

[0064] It is understood that the oral compositions, formulations, and methods described herein include the use of crystalline forms, amorphous phases, and / or pharmaceutically acceptable salts, solvates, hydrates, and conformers of the compounds of some embodiments, as well as metabolites and active metabolites of these compounds with the same type of activity. Conformers are conformational isomers. Conformational isomerism is the phenomenon of molecules with the same structural formula but different conformations (conformers) in terms of the arrangement of atoms around a rotatable bond. In certain embodiments, the compounds described herein exist in solvated forms with pharmaceutically acceptable solvents such as water, ethanol, etc. In other embodiments, the compounds described herein exist in unsolvated forms. Solvates contain either stoichiometric or non-stoichiometric solvents and may be formed during the process of crystallization with pharmaceutically acceptable solvents such as water, ethanol, etc. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. In addition, the compounds provided herein can exist in unsolvated and solvated forms. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the compounds and methods provided herein. Other forms in which the compounds of some embodiments may be provided may include amorphous, milled, and nanoparticulate forms.

[0065] Similarly, it is understood that the compounds described herein, e.g., compounds of some embodiments, include the compounds in any of the forms described herein (e.g., pharmaceutically acceptable salts, prodrugs, crystalline forms, amorphous forms, solvated forms, enantiomeric forms, tautomeric forms, etc.).

[0066] composition In aspects, disclosed herein are compositions comprising one or more compounds described herein and a carrier. In some embodiments, one or more compounds are derived from a plant. In some embodiments, one or more compounds are derived from a cell. In some embodiments, one or more compounds are synthetically produced. In some embodiments, the composition is an oral composition.

[0067] In some embodiments, the composition comprises a plant extract containing one or more compounds described herein and a carrier. As used herein, "extract" refers to a composition containing a desired target compound separated from other substances present in the naturally occurring material from which the oral composition is obtained. Plant extracts can be obtained from any plant tissue, including whole plants; plant parts such as shoot vegetative organs / structures (e.g., leaves, stems, and tubers), roots, flowers and floral organs / structures (e.g., bracts, sepals, petals, stamens, ovaries, anthers, and ovaries), seeds (including embryos, endosperm, and seed coats), and fruits (mature ovaries); plant tissues (e.g., vascular tissue, aboveground tissue, etc.); or cells (e.g., guard cells, egg cells, etc.), and their progeny, cultures, or cell lines. In some embodiments, the extract is generally recognized as safe for human consumption. Thus, in certain embodiments, the extract is derived from an edible source. In this regard, the extract is an edible extract. Extracts can be prepared by freezing, crushing, soaking, grinding, and / or fermenting the desired material, subjecting the material to solvent extraction, and separating the insoluble and soluble materials. In this regard, the "extract" of the present disclosure can be, but is not limited to, crude, fractionated, sub-fractionated, separated, isolated, concentrated, or purified.

[0068] In some embodiments, a plant extract may be a crude extract. As used herein, "crude" refers to a compound or molecule that has not been completely separated from the components of the original composition in which it was present. In embodiments relating to fractions or subfractions, molecules in a crude extract may be subjected to partial separation to obtain a less crude extract containing other substances. In comparison, the term "isolated" means that a compound or molecule is substantially enriched or purified with respect to the complex cellular environment in which it naturally occurs, such as in a crude extract. When an isolated molecule is enriched or purified, the absolute level of purity is not critical, and one of skill in the art can easily determine an appropriate level of purity depending on the intended use of the material. In some cases, an isolated molecule forms part of a composition that may contain other components (e.g., a more or less crude extract containing many other substances), for example. In other situations, an isolated molecule may be purified to essential homogeneity, as determined, for example, by spectrophotometry, NMR, or chromatography (e.g., LC-MS).

[0069] Suitable solvents for preparing extracts include, for example, n-pentane, hexane, butane, chloroform, dichloromethane, diethyl ether, acetonitrile, water, butanol, isopropanol, ethanol, methanol, glacial acetic acid, acetone, norflurane (HFA134a), ethyl acetate, dimethyl sulfoxide, heptafluoropropane (HFA227), and subcritical or supercritical fluids, such as liquid carbon dioxide and water, or combinations thereof in any proportion. When solvents such as those mentioned above are used, the resulting extract typically contains nonspecific, lipid-soluble substances. This can be removed by various processes, including "dewaxing," which involves cooling to a predetermined temperature (usually -20°C) and then removing the waxy ballast by filtration or centrifugation, extraction with subcritical or supercritical carbon dioxide or a nonpolar solvent (e.g., hexane), and distillation.

[0070] In some embodiments, the plant extract comprises Eupatorium perfoliatum. In some embodiments, the plant extract comprises a purified or crude extract of Eupatorium perfoliatum. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from leaves. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from flowers. In some embodiments, the extract may be derived directly from roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove oils before proceeding with the extraction process. In some embodiments, the plant extract comprises 3',4',5,7-tetrahydroxy-3-[α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranosyloxy]flavone. In some embodiments, the plant extract comprises 3,3',4',5,7-pentahydroxyflavone. In some embodiments, the plant extract comprises compound 13. In some embodiments, the plant extract comprises compound 14.

[0071] In some embodiments, the plant extract comprises Zingiber officinale. In some embodiments, the plant extract comprises a purified or crude extract of Zingiber officinale. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0072] In some embodiments, the plant extract comprises Picea sitchensis. In some embodiments, the plant extract comprises a purified or crude extract of Picea sitchensis. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0073] In some embodiments, the plant extract comprises Viburnum davidii. In some embodiments, the plant extract comprises a purified or crude extract of Viburnum davidii. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process. In some embodiments, the plant extract comprises 1-(2-hydroxy-4-{[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}phenyl)-3-(4-hydroxyphenyl)propan-1-one. In some embodiments, the plant extract comprises 3-(4-hydroxyphenyl)-1-[4-hydroxy-2-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]propan-1-one. In some embodiments, the plant extract comprises 4'-O-methyl davidioside. In some embodiments, the plant extract comprises compound 16. In some embodiments, the plant extract comprises compound 17. In some embodiments, the plant extract comprises compound 19.

[0074] In some embodiments, the plant extract comprises Arnica montana. In some embodiments, the plant extract comprises a purified or crude extract of Arnica montana. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process. In some embodiments, the plant extract comprises 3,4',5,7-tetrahydroxyflavone. In some embodiments, the plant extract comprises Compound 12.

[0075] In some embodiments, the plant extract comprises Helianthus annuus. In some embodiments, the plant extract comprises a purified or crude extract of Helianthus annuus. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0076] In some embodiments, the plant extract comprises Lactuca sativa. In some embodiments, the plant extract comprises a purified or crude extract of Lactuca sativa. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0077] In some embodiments, the plant extract comprises Barnadesia spinosa. In some embodiments, the plant extract comprises a purified or crude extract of Barnadesia spinosa. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0078] In some embodiments, the plant extract comprises Dolomiaea souliei. In some embodiments, the plant extract comprises a purified or crude extract of Dolomiaea souliei. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0079] In some embodiments, the plant extract comprises Saussurea costus. In some embodiments, the plant extract comprises a purified or crude extract of Saussurea costus. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0080] In some embodiments, the plant extract comprises Artemisia annua. In some embodiments, the plant extract comprises a purified or crude extract of Artemisia annua. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0081] In some embodiments, the plant extract comprises Inula helenium. In some embodiments, the plant extract comprises a purified or crude extract of Inula helenium. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0082] In some embodiments, the plant extract comprises Laurus nobilis. In some embodiments, the plant extract comprises a purified or crude extract of Laurus nobilis. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0083] In some embodiments, the plant extract comprises Momoca cochinchinensis. In some embodiments, the plant extract comprises a purified or crude extract of Momoca cochinchinensis. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0084] In some embodiments, the plant extract comprises Pogostemon cablin. In some embodiments, the plant extract comprises a purified or crude extract of Pogostemon cablin. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0085] In some embodiments, the plant extract comprises Cichorium intybus. In some embodiments, the plant extract comprises a purified or crude extract of Cichorium intybus. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0086] In some embodiments, the plant extract comprises Solidago Canadensis. In some embodiments, the plant extract comprises a purified or crude extract of Solidago Canadensis. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0087] In some embodiments, the plant extract comprises Horeum vulgare. In some embodiments, the plant extract comprises a purified or crude extract of Horeum vulgare. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0088] In some embodiments, the plant extract comprises Triticum aestivum. In some embodiments, the plant extract comprises a purified or crude extract of Triticum aestivum. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0089] In some embodiments, the plant extract comprises Silene conica. In some embodiments, the plant extract comprises a purified or crude extract of Silene conica. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0090] In some embodiments, the plant extract comprises Alloteropsis semialata. In some embodiments, the plant extract comprises a purified or crude extract of Alloteropsis semialata. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0091] In some embodiments, the plant extract comprises Paris polyphylla. In some embodiments, the plant extract comprises a purified or crude extract of Paris polyphylla. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0092] In some embodiments, the plant extract comprises Camella sinensis. In some embodiments, the plant extract comprises a purified or crude extract of Camella sinensis. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0093] In some embodiments, the plant extract comprises Hordeum vulgare. In some embodiments, the plant extract comprises a purified or crude extract of Hordeum vulgare. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0094] In some embodiments, the plant extract comprises Setaria italicum. In some embodiments, the plant extract comprises a purified or crude extract of Setaria italicum. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0095] In some embodiments, the plant extract comprises Zea mays. In some embodiments, the plant extract comprises a purified or crude extract of Zea mays. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the seeds, leaves, and / or flowers may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0096] In some embodiments, the plant extract comprises Arabidopsis thaliana. In some embodiments, the plant extract comprises a purified or crude extract of Arabidopsis thaliana. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from leaves. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from flowers. In some embodiments, the extract may be derived directly from roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0097] In some embodiments, the plant extract comprises Brachypodium distachyon. In some embodiments, the plant extract comprises a purified or crude extract of Brachypodium distachyon. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0098] In some embodiments, the plant extract comprises Grindelia integrifolia. In some embodiments, the plant extract comprises a purified or crude extract of Grindelia integrifolia. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0099] In some embodiments, the plant extract comprises Lobelia chinesis. In some embodiments, the plant extract comprises a purified or crude extract of Lobelia chinesis. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0100] In some embodiments, the plant extract comprises Arachis hypogaea. In some embodiments, the plant extract comprises a purified or crude extract of Arachis hypogaea. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0101] In some embodiments, the plant extract comprises Nepenthes khasiana. In some embodiments, the plant extract comprises a purified or crude extract of Nepenthes khasiana. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0102] In some embodiments, the plant extract comprises Selaginella mollendorffii. In some embodiments, the plant extract comprises a purified or crude extract of Selaginella mollendorffii. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0103] In some embodiments, the plant extract comprises Selaginella mollendorffii. In some embodiments, the plant extract comprises a purified or crude extract of Selaginella mollendorffii. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0104] In some embodiments, the plant extract comprises Taxus x media. In some embodiments, the plant extract comprises a purified or crude extract of Taxus x media. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0105] In some embodiments, the plant extract comprises Acorus gramieus. In some embodiments, the plant extract comprises a purified or crude extract of Acorus gramieus. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0106] In some embodiments, the plant extract comprises Andrographis paniculata. In some embodiments, the plant extract comprises a purified or crude extract of Andrographis paniculata. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0107] In some embodiments, the plant extract comprises Artemisia maritima. In some embodiments, the plant extract comprises a purified or crude extract of Artemisia maritima. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0108] In some embodiments, the plant extract comprises Bletilla striata. In some embodiments, the plant extract comprises a purified or crude extract of Bletilla striata. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0109] In some embodiments, the plant extract comprises Fallopia multflora. In some embodiments, the plant extract comprises a purified or crude extract of Fallopia multflora. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0110] In some embodiments, the plant extract comprises Gossypium hirsutum. In some embodiments, the plant extract comprises a purified or crude extract of Gossypium hirsutum. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0111] In some embodiments, the plant extract comprises Hordeum spontaneum. In some embodiments, the plant extract comprises a purified or crude extract of Hordeum spontaneum. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0112] In some embodiments, the plant extract comprises Hypericum perforatum. In some embodiments, the plant extract comprises a purified or crude extract of Hypericum perforatum. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0113] In some embodiments, the plant extract comprises Musa acuminate. In some embodiments, the plant extract comprises a purified or crude extract of Musa acuminate. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0114] In some embodiments, the plant extract comprises Oryza rufipogon. In some embodiments, the oral composition comprises an extract of Oryza rufipogon. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0115] In some embodiments, the plant extract comprises Oryza sativa. In some embodiments, the plant extract comprises a purified or crude extract of Oryza sativa. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0116] In some embodiments, the plant extract comprises Quercus suber. In some embodiments, the plant extract comprises a purified or crude extract of Quercus suber. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0117] In some embodiments, the plant extract comprises Solanum tuberosum. In some embodiments, the plant extract comprises a purified or crude extract of Solanum tuberosum. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0118] In some embodiments, the plant extract comprises Valeriana officinallis. In some embodiments, the plant extract comprises a purified or crude extract of Valeriana officinallis. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0119] In some embodiments, the plant extract comprises Vitis vinifera. In some embodiments, the plant extract comprises a purified or crude extract of Vitis vinifera. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from leaves. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from flowers. In some embodiments, the extract may be derived directly from roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove oils before proceeding with the extraction process.

[0120] In some embodiments, the plant extract comprises Polygonatum odoratum. In some embodiments, the plant extract comprises a purified or crude extract of Polygonatum odoratum. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0121] In some embodiments, the plant extract comprises Glycine max. In some embodiments, the plant extract comprises a purified or crude extract of Glycine max. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0122] In some embodiments, the plant extract comprises Panicum virgatum cv. Trailblazer. In some embodiments, the plant extract comprises a purified or crude extract of Panicum virgatum cv. Trailblazer. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0123] In some embodiments, the plant extract comprises Populus trichorarpa. In some embodiments, the plant extract comprises a purified or crude extract of Populus trichorarpa. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process.

[0124] In some embodiments, the plant extract comprises Eruca vesicaria. In some embodiments, the plant extract comprises a purified or crude extract of Eruca vesicaria. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from leaves. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from flowers. In some embodiments, the extract may be derived directly from roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove oils before proceeding with the extraction process. In some embodiments, the plant extract comprises [(2R,3S,4S,5R,6S)-6-{[2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-3-yl]oxy}-3,4,5-trihydroxyoxan-2-yl]methyl(2E)-3-(4-hydroxyphenyl)prop-2-enoate. In some embodiments, the plant extract comprises compound 22.

[0125] In some embodiments, the plant extract comprises Gynura procumbens. In some embodiments, the plant extract comprises a purified or crude extract of Gynura procumbens. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from leaves. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from flowers. In some embodiments, the extract may be derived directly from roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove oils before proceeding with the extraction process. In some embodiments, the plant extract comprises 7-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-3,5-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one. In some embodiments, the plant extract comprises compound 21.

[0126] In some embodiments, the plant extract comprises Clausena excavata. In some embodiments, the plant extract comprises a purified or crude extract of Clausena excavata. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from leaves. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from flowers. In some embodiments, the extract may be derived directly from roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove oils before proceeding with the extraction process. In some embodiments, the plant extract comprises 3-[(2S,5R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2S,3S,5R)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one. In some embodiments, the plant extract comprises Compound 20. In some embodiments, the plant extract comprises compound 24.

[0127] In some embodiments, the plant extract comprises Psidium guajava. In some embodiments, the plant extract comprises a purified or crude extract of Psidium guajava. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the leaves. In some embodiments, the extract may be derived directly from the whole seeds. In some embodiments, the extract may be derived directly from the flowers. In some embodiments, the extract may be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process. In some embodiments, the plant extract comprises 3-[(2S,3R,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one. In some embodiments, the plant extract comprises compound 27.

[0128] In some embodiments, the plant extract comprises Senna alexandrina. In some embodiments, the plant extract comprises a purified or crude extract of Senna alexandrina. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the leaf. In some embodiments, the extract may be derived directly from the whole seed. In some embodiments, the extract may be derived directly from the flower. In some embodiments, the extract may be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove the oil before proceeding with the extraction process. In some embodiments, the plant extract comprises 3-(((2R,3S,4R,5R,6S)-4,5-dihydroxy-6-(hydroxymethyl)-3-(((2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one. In some embodiments, the plant extract comprises compound 23. In some embodiments, the plant extract comprises compound 26.

[0129] In some embodiments, the plant extract comprises Tanacetum parthenium. In some embodiments, the plant extract comprises a purified or crude extract of Tanacetum parthenium. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from leaves. In some embodiments, the extract may be derived directly from whole seeds. In some embodiments, the extract may be derived directly from flowers. In some embodiments, the extract may be derived directly from roots. In some embodiments, the seeds, leaves, flowers, and / or roots may be ground into a powder, which is then heated to a temperature selected from the range of about 30-100°C to remove oils before proceeding with the extraction process. In some embodiments, the plant extract comprises 1,6-dihydroxy-3-methyl-8-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyanthracene-9,10-dione. In some embodiments, the plant extract comprises 3,6-dimethoxyapigenin. In some embodiments, the plant extract comprises Compound 30.

[0130] In some embodiments, the oral composition comprises an extract from one or more plant sources. In some embodiments, the oral composition comprises an extract from two or more plant sources. In some embodiments, the oral composition comprises an extract from three or more plant sources.

[0131] In some embodiments, the extracts described herein include juices, infusions, and fermentation residues. The fermented plant-derived extracts or processed fractions thereof are used in ingestible compositions, such as health-promoting compositions or tonics for humans and animals.

[0132] In some embodiments, the composition comprises about 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% w / w of one or more compounds or extracts disclosed herein, or a range including and / or spanning the aforementioned values. In some embodiments, the composition comprises about 0.1% to about 10% of one or more compounds or extracts as described herein. In some embodiments, the composition comprises about 0.1% to about 5% of one or more compounds or extracts as described herein. In some embodiments, the composition comprises about 1% to about 10% of one or more compounds or extracts as described herein. In some embodiments, when one or more compounds or extracts of the present disclosure are provided or administered to humans and animals as pharmaceuticals, nutritional supplements, or dietary supplements, they may be provided by themselves or as compositions containing 0.1-99% active ingredient, for example, in combination with an acceptable carrier. In some embodiments, a compound or extract of the present disclosure may be provided or administered at about 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% w / w, or a range including and / or spanning the aforementioned values. In some embodiments, a plant extract described herein comprises one or more compounds selected from Table A. In some embodiments, a composition described herein comprises one or more compounds selected from Table A. In some embodiments, the one or more compounds selected from Table A include compounds 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, or a combination thereof.

[0133] In some embodiments, compositions may include one or more compounds described herein and a suitable carrier or excipient, in some embodiments, one or more compounds described herein may be in a ratio of about 10:1 to about 1:10, or a range including and / or spanning the aforementioned values. In some embodiments, one or more compounds described herein may be in a ratio of about 10:1, 9.5:1, 8.5:1, 8.0:1, 7.5:1, 7:1, 6.5:1, 6:1, 5.5:1, 5:1, 4.5:1, 4:1, 3.5:1, 3.0:1, 2.5:1, 2.0:1, 1.5:1, 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5, 1:10. In some embodiments, the composition comprises one or more compounds selected from Table A. In some embodiments, the one or more compounds selected from Table A include compounds 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, or a combination thereof.

[0134] In some embodiments, the disclosure provided herein provides a composition comprising one or more compounds described herein and a carrier. In some embodiments, the carrier is an acceptable carrier suitable for oral ingestion. In some embodiments, the acceptable carrier is a pharmaceutically acceptable carrier. In some embodiments, the acceptable carrier is a food-grade carrier. In some embodiments, the one or more compounds are substantially pure compounds. In some embodiments, the composition is an oral composition. As used herein, the term "carrier" refers to a material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, manufacturing aid (e.g., lubricant, magnesium talc, calcium or zinc stearate, stearic acid), or solvent encapsulating material, that is involved in carrying or transporting a compound of interest from one organ or part of the body to another. Each carrier must be compatible with the other ingredients of the formulation and not harmful to the subject.Some examples of substances that can function as carriers include: (1) sugars, such as lactose, glucose, fructose, maltose, and sucrose; (2) starches, such as corn starch, tapioca starch, rice starch, wheat starch, and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethylcellulose, microcrystalline cellulose, methylcellulose, ethylcellulose, cellulose acetate, and hydroxypropylmethylcellulose; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter, carnauba wax, beeswax, paraffin wax, candelilla wax, shellac wax, rice bran wax, and suppository wax; and (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, and olive oil. , corn oil, and soybean oil; (10) glycols such as propylene glycol and glycerol (glycerin); (11) polyols such as glycerin, xylitol, erythritol, maltitol, isomalt, lactitol, sorbitol, mannitol, and polyethylene glycol; (12) esters such as ethyl oleate and ethyl laurate; (13) agar, (14) buffers 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) pH buffers; (21) polyesters, polycarbonates, and / or polyanhydrides; (22) lipids and / or phospholipids; and (23) other non-toxic, compatible materials employed in conventional formulations.Examples of food-grade carriers include vegetable proteins, soy proteins, ion exchangers, soft gels, oils, alumina, aluminum stearate, lecithin, serum proteins such as human serum albumin, phosphates, buffer substances such as glycine, sorbic acid, and potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salt, or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, and polyvinylpyrrolidone, cellulose-based substances, PEG, maltodextrin, calcium carbonate, dicalcium phosphate, tricalcium phosphate, microcrystalline cellulose, dextrose, rice flour, magnesium stearate, stearic acid, croscarmellose sodium, sodium starch glycolate, crospovidone, sucrose, vegetable gums, lactose, methylcellulose, povidone, carboxymethylcellulose, corn starch, and mixtures thereof. Other examples of pharmaceutically acceptable carriers are described, for example, in AN'EL'S PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY SYSTEMS (9th Ed., Lippincott Williams and Wilkins (2010)), PHARMACEUTICAL SCIENCES (8th Ed., Mack Publishing Co. (1990)), or REMINGTON: THE SCIENCE AND PRACTICE OF PHARMACY (1st Ed., Lippincott Williams & Wilkins (2005), which are incorporated in their entirety. In some embodiments, the carrier is about 0.5% to about 80% (w / w) of the composition. In some embodiments, the carrier is about 0.5%, about 1.0%, about 1.5%, about 2.0%, about 2.5%, about 3.0%, about 3.5%, about 4.0%, about 4.5%, about 5.0%, about 7.5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 70%, about 75%, about 80% (w / w) of the composition, or ranges including, between, and / or spanning the aforementioned values.

[0135] In some embodiments, the oral composition may further comprise a preservative, in some embodiments, the preservative may be in an amount of about 0.01%, 0.05%, 0.1%, 0.15%, 0.20%, 0.25%, 0.50%, 0.75%, 1.0%, 1.25%, 1.50%, 1.75%, 2.0%, 2.25%, 2.50%, 2.75%, 3.0%, 3.25%, 3.5%, 3.75%, 4.0%, 4.25%, 4.5%, 4.75%, 5.0% w / w, or a range inclusive and / or spanning the aforementioned values. In some embodiments, the preservative may be selected from the group consisting of, but not limited to, sodium benzoate, methylparaben, propylparaben, sodium nitrite, sulfur dioxide, sodium sorbate, ascorbic acid, tocopherol, calcium propionate, citric acid, sorbic acid, tocopherol, calcium propionate, citric acid, sorbic acid, butylated hydroxotoluene (BHT), butylated hydroxyanisole (BHA), alcohol, such as ethyl alcohol, rosemary extract, and potassium sorbate. Other suitable preservatives include, but are not limited to, salts of edetic acid (also known as ethylenediaminetetraacetic acid, or EDTA, e.g., disodium EDTA).

[0136] In some embodiments, the oral composition may further comprise a sweetener. In some embodiments, the sweetener may be present in an amount of about 1.0%, 1.25%, 1.50%, 1.75%, 2.0%, 2.25%, 2.50%, 2.75%, 3.0%, 3.25%, 3.5%, 3.75%, 4.0%, 4.25%, 4.5%, 4.75%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0% w / w, or a range inclusive of and / or spanning the aforementioned values. In some embodiments, the sweetener may comprise a natural sweetener. In some embodiments, the sweetener may comprise a synthetic sweetener. Non-limiting examples of sweetening agents include sucrose, dextrose, maltose, dextrin, anhydrous invert sugar, fructose, high fructose corn syrup, levulose, galactose, corn syrup solids, tagatose, polyols (e.g., sorbitol, mannitol, xylitol, lactitol, erythritol, and maltitol), hydrogenated starch hydrolysates, isomalt, trehalose, and mixtures thereof.

[0137] In some embodiments, the oral composition may further comprise a flavoring agent. In some embodiments, the flavoring agent may be present in an amount of about 1.0%, 1.25%, 1.50%, 1.75%, 2.0%, 2.25%, 2.50%, 2.75%, 3.0%, 3.25%, 3.5%, 3.75%, 4.0%, 4.25%, 4.5%, 4.75%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0% w / w, or a range inclusive of and / or spanning the foregoing values. In some embodiments, the flavoring agent may comprise a natural or artificial flavor. In certain embodiments, the flavoring agent comprises an essential oil, such as an oil derived from a plant or fruit, such as peppermint oil, spearmint oil, other mint oils, clove oil, cinnamon oil, oil of wintergreen, bay leaf, thyme, cedar leaf, nutmeg, allspice, sage, mace, and almond. In another particular embodiment, the flavoring agent comprises a plant extract or fruit extract, such as apple, banana, watermelon, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot, and mixtures thereof. In yet another particular embodiment, the flavoring agent comprises a citrus flavoring, such as an extract, essence, or oil of lemon, lime, orange, tangerine, grapefruit, citron, kumquat, etc.

[0138] In some embodiments, the oral composition may further comprise a colorant, which may be in an amount of about 1.0%, 1.25%, 1.50%, 1.75%, 2.0%, 2.25%, 2.50%, 2.75%, 3.0%, 3.25%, 3.5%, 3.75%, 4.0%, 4.25%, 4.5%, 4.75%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0% w / w, or a range inclusive and / or spanning the aforementioned values.

[0139] In some embodiments, the oral composition may further comprise at least one additive. In some embodiments, the additive may be present in an amount of about 1.0%, 1.25%, 1.50%, 1.75%, 2.0%, 2.25%, 2.50%, 2.75%, 3.0%, 3.25%, 3.5%, 3.75%, 4.0%, 4.25%, 4.5%, 4.75%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0% w / w, or a range inclusive and / or spanning the foregoing values. In some embodiments, the at least one additive may be an emulsifier. In some embodiments, the additive may comprise one or more vitamins. In some embodiments, the additive may comprise one or more minerals. In some embodiments, the additive may comprise a stabilizer.

[0140] In some embodiments, the compositions described herein may include two or more compounds of Formula (I), (IA), (IB), (II), or (III). In some embodiments, the two or more compounds described herein may be in a ratio of about 10:1 to about 1:10, or a range including and / or spanning the aforementioned values. In some embodiments, the ratio of two or more compounds described herein may be about 10:1, 9.5:1, 8.5:1, 8.0:1, 7.5:1, 7:1, 6.5:1, 6:1, 5.5:1, 5:1, 4.5:1, 4:1, 3.5:1, 3.0:1, 2.5:1, 2.0:1, 1.5:1, 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5, 1:10. In some embodiments, the two or more compounds may be selected from Table A, a salt, or an isomer thereof. In some embodiments, two or more compounds selected from Table A include Compound 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, or a combination thereof. In some embodiments, one of the two or more compounds includes Compound 12. In some embodiments, one of the two or more compounds includes Compound 13. In some embodiments, one of the two or more compounds includes Compound 14. In some embodiments, one of the two or more compounds includes Compound 15. In some embodiments, one of the two or more compounds includes Compound 16. In some embodiments, one of the two or more compounds includes Compound 17. In some embodiments, one of the two or more compounds includes Compound 18. In some embodiments, one of the two or more compounds includes Compound 19. In some embodiments, one of the two or more compounds includes Compound 20. In some embodiments, one of the two or more compounds includes Compound 21. In some embodiments, one of the two or more compounds includes Compound 22. In some embodiments, one of the two or more compounds comprises compound 23.In some embodiments, one of the two or more compounds comprises compound 24. In some embodiments, one of the two or more compounds comprises compound 25. In some embodiments, one of the two or more compounds comprises compound 26. In some embodiments, one of the two or more compounds comprises compound 27. In some embodiments, one of the two or more compounds comprises compound 28. In some embodiments, one of the two or more compounds comprises compound 29. In some embodiments, one of the two or more compounds comprises compound 30. In some embodiments, one of the two or more compounds comprises compound 31. In some embodiments, one of the two or more compounds comprises compound 32. In some embodiments, one of the two or more compounds comprises compound 33. In some embodiments, one of the two or more compounds comprises compound 34. In some embodiments, one of the two or more compounds comprises compound 35. In some embodiments, one of the two or more compounds comprises compound 36. In some embodiments, one of the two or more compounds comprises compound 37. In some embodiments, one of the two or more compounds comprises compound 38. In some embodiments, the two or more compounds comprise at least two of compounds 14, 22, 23, 26, and 30. In some embodiments, the two or more compounds are present in a ratio of about 10:1 to about 1:10. In some embodiments, the two or more compounds are present in a ratio of about 5:1 to about 1:5. In some embodiments, the two or more compounds are present in a ratio of about 2.5:1 to about 2:1. In some embodiments, the two or more compounds are present in a ratio of about 2.5:1 to about 1:2.5. In some embodiments, the two or more compounds are in a ratio of about 5:1. In some embodiments, the two or more compounds are in a ratio of about 4:1. In some embodiments, the two or more compounds are in a ratio of about 3:1. In some embodiments, the two or more compounds are in a ratio of about 2:1. In some embodiments, the two or more compounds are in a ratio of about 1:1. In some embodiments, the two or more compounds are in a ratio of about 1:2. In some embodiments, the two or more compounds are in a ratio of about 1:3. In some embodiments, the two or more compounds are in a ratio of about 1:4.In some embodiments, the two or more compounds are in a ratio of about 1:5. In some embodiments, the oral composition comprises a compound of Formula (III) but does not include a compound selected from the group of compounds 30, 31, or a combination thereof. In some embodiments, the oral composition comprises two or more compounds of Formula (I), (IA), (IB), (II), or (III) but does not include a compound selected from the group of compounds 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, or a combination thereof. In some embodiments, the oral composition consists essentially of compounds 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, or combinations thereof that are not bound to lignocellulosic material. In some embodiments, the oral composition comprises two or more compounds selected from compounds 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, or combinations thereof, with the proviso that the two or more compounds are not bound to lignin, cellulose, and / or pectin in the oral composition. In some embodiments, the oral composition comprises two or more compounds selected from compounds 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, or a combination thereof, with the proviso that the two or more compounds are not derived from a natural source extract or extracted from a natural source, e.g., a plant.

[0141] In some embodiments, the oral composition may consist essentially of one or more compounds described herein that are not bound to lignocellulosic material. Lignocellulosic material refers to a composite material primarily composed of lignin, cellulose, and hemicellulose. These are naturally occurring polymers found in plant cell walls. Lignocellulosic material is characterized by a rigid structure, high strength, and resistance to degradation. This material is generally derived from wood, grass, and the inedible parts of plants. In some embodiments, the composition does not contain lignin, cellulose, and / or pectin. In some embodiments, the composition does not contain extracts derived from natural sources.

[0142] In some embodiments, the oral composition comprises a compound of Formula (I) selected from the group consisting of compounds 12, 13, 14, 15, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 33, 34, and 35. In some embodiments, the oral composition comprises a compound of Formula (I) selected from the group consisting of compounds 14, 22, 23, and 26. In some embodiments, the oral composition comprises a compound of Formula (I) selected from the group consisting of compounds 22 and 23. In some embodiments, the oral composition comprises a compound of Formula (I) and a compound of Formula (II). In some embodiments, the compound of Formula (II) is selected from the group consisting of compounds 16, 17, 18, and 19. In some embodiments, the oral composition comprises a compound of Formula (I) and a compound of Formula (III). In some embodiments, the compound of Formula (III) is Compound 30 or 31. In some embodiments, the oral composition comprises a compound of Formula (II) and a compound of Formula (III). In some embodiments, the oral composition comprises two or more compounds selected from Table A. In some embodiments, the oral composition comprises a compound of formula (I) but does not include a compound selected from the group of compounds 12, 13, 14, 15, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 33, 34, 35, or a combination thereof. In some embodiments, the oral composition comprises a compound of formula (II) but does not include a compound selected from the group of compounds 16, 17, 18, 19, or a combination thereof. In some embodiments, the oral composition comprises a compound of Formula (III) but does not include a compound selected from the group of compounds 30, 31, or a combination thereof. In some embodiments, the oral composition comprises one or more compounds of Formula (I), (IA), (IB), (II), or (III) but does not include a compound selected from the group of compounds 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, or a combination thereof.In some embodiments, the oral composition consists essentially of compounds 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, or combinations thereof that are not bound to lignocellulosic material. In some embodiments, the oral composition comprises one or more compounds selected from compounds 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, or combinations thereof, with the proviso that the one or more compounds are not bound to lignin, cellulose, and / or pectin in the oral composition. In some embodiments, the oral composition comprises one or more compounds selected from compounds 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, or a combination thereof, provided that the one or more compounds are not derived from a natural source extract or extracted from a natural source, e.g., a plant.

[0143] formulation Aspects of the present disclosure relate to formulations comprising one or more compounds described herein. In some embodiments, a substantially pure compound or extract comprising one or more compounds of the present disclosure can be combined with a carrier and provided in any form suitable for consumption by, provision to, or administration to a subject. In some embodiments, one or more compounds or an extract comprising one or more compounds is added to a consumable product as an exogenous ingredient or additive. Suitable intake forms include, but are not limited to, a dietary supplement, a food ingredient or additive, a food, a medical food, a nutraceutical composition, or a pharmaceutical composition. In some embodiments, one or more compounds or an extract comprising one or more compounds is provided in either liquid, granular, or powder form. In some embodiments, the formulation may be a food product.

[0144] The compositions containing the plant extracts or compounds of the present disclosure can be combined with a carrier and provided in any suitable form for ingestion by or administration to a subject. In this regard, the plant extracts or compounds are added to consumables as an exogenous ingredient or additive. Suitable ingestion forms include, but are not limited to, dietary supplements, food ingredients or additives, medical foods, nutraceutical compositions, or pharmaceutical compositions. In some embodiments, the plant extracts or compounds are provided in either liquid or powder form.

[0145] A food ingredient or additive is an edible substance intended, directly or indirectly, to be a component of or affect the properties of a food (including substances intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food). Foods, particularly functional foods, are foods that have been fortified or concentrated during processing to contain additional, complementary nutrients and / or beneficial ingredients. Foods according to the present disclosure can be in the form of, for example, butter, margarine, sweet or savory spreads, condiments, biscuits, health bars, bread, cakes, cereals, candy, confectionery, soups, milk, yogurt, or fermented dairy products, cheese, juice-based and vegetable-based beverages, fermented beverages, shakes, flavored waters, teas, oils, or any other suitable food product. In some embodiments, the food is a whole food in which the concentration of a compound has been concentrated through specific post-harvest and food-manufacturing processing methods to a level that provides an effective amount of the compound. In some embodiments, the food comprises one or more compounds described herein and a fiber source. In some embodiments, the food comprises one or more compounds described herein. In some embodiments, the food is a food bar. In some embodiments, the food bar comprises from about 0.01% to about 20% (w / w) of one or more compounds described herein. In some embodiments, the food bar comprises from about 0.1% to about 10% (w / w) of one or more compounds described herein. In some embodiments, the food product is a crisp. In some embodiments, the food crisp comprises from about 0.01% to about 20% (w / w) of one or more compounds described herein. In some embodiments, the food crisp comprises from about 0.1% to about 10% (w / w) of one or more compounds described herein.

[0146] The compounds, compositions, and extracts of the present disclosure can be prepared as nutritional formulations, such as foods, including medical foods or functional foods. A "medical food or functional food" is defined as a food that is consumed as part of a normal diet but that has been demonstrated to have physiological benefits beyond its basic nutritional function and / or reduce the risk of a disease or condition, such as a chronic disease. By way of example and not limitation, medical foods and functional foods may contain one or more of the following ingredients: compounds described herein, compositions described herein, extracts described herein, vitamins, minerals, herbs, botanicals, amino acids, dietary substances intended to supplement the diet by increasing total dietary intake, concentrates, metabolites, ingredients, extracts, or any combination of the foregoing. Dietary supplements may also be incorporated into foodstuffs, such as functional foods, designed to promote health or prevent disease or disorders. When administered as a pharmaceutical formulation, the composition can be administered to a patient in any of several ways, either prophylactically or therapeutically. In some embodiments, the compositions described herein may be administered alone or in combination with other additives or pharmaceutical agents, and may be combined with a physiologically acceptable carrier. The effective amount and method and purpose of administration of a particular formulation may vary based on the individual subject, the stage of the disease or condition, and other factors apparent to one skilled in the art. For pharmaceutical formulations, as with nutritional supplements, the concentration of the subject composition may be monitored (e.g., plasma levels may be monitored) during the course of treatment to ensure that the desired level is maintained.

[0147] In some embodiments, the food product contains carbohydrates. Various carbohydrates, such as various sugars and starches, are used in foods. Carbohydrates are an important source of energy for the body and include complex carbohydrates (such as whole grains and vegetables) and simple carbohydrates (such as sugars and refined grains). Several common carbohydrates are used in foods, including starch, sugar, fructose, maltodextrin, dextrose, corn syrup, oligosaccharides, cellulose, and complex carbohydrates, such as inulin, which can be added to processed foods as a prebiotic fiber. According to the present disclosure, the concentration of carbohydrates can vary depending on the intended use of the product. In some embodiments, carbohydrates can comprise from about 1% to about 95% by weight of the food product. In some embodiments, carbohydrates can comprise from about 1% to about 95% by weight of the food product. In some embodiments, the food product may comprise carbohydrates in a range of about 1%, 3%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or ranges of higher and lower values ​​independently selected from ranges including, between, and / or spanning the aforementioned values.

[0148] In some embodiments, foods may contain sugars. Sugars such as high-fructose corn syrup, sucrose, glucose syrup, dextrose, and other sweeteners are often added to processed foods to make them more palatable. Additionally, sugar alcohols or maltodextrins may be added to foods to reduce the calorie content of the product and / or enhance its nutritional profile. In some embodiments, foods may contain one or more sugars that are slowly or incompletely digestible by humans, if not completely indigestible. These sugars may include isomaltose, panose, and branched oligomers with a degree of polymerization of four or more. Additional non-limiting examples of sugars include sucrose, HFCS, fructose, brown sugar (which may be partially or fully refined), powdered sugar (also known as confectioner's sugar), high fructose corn syrup, honey, molasses, maple syrup, agave nectar, coconut sugar, jujube sugar, fruit juice concentrate, maltodextrin, dextrose, glucose syrup, maple syrup, molasses, and lactose. According to the present disclosure, the concentration of sugars may vary depending on the intended use of the product. In some embodiments, sugars may comprise from about 1% to about 95% by weight of the food product. In some embodiments, the sugar(s) component comprises from about 2% to about 10% by weight of the composition. In some embodiments, sugars may comprise from about 1% to about 95% by weight of the food product. In some embodiments, the food product may comprise sugars in a range of high and low values ​​independently selected from about 1%, 3%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or ranges including, between, and / or spanning the aforementioned values.

[0149] In some embodiments, the food product comprises a fiber source. In some embodiments, the food product comprises about 5% to about 30% (w / w) fiber. In some embodiments, the food product comprises at least 10% fiber. In some embodiments, the food product comprises at least 15% fiber. In some embodiments, the food product comprises at least 20% fiber. In some embodiments, the food product comprises at least 30% fiber. In some embodiments, the fiber may be selected from psyllium husk, inulin, beta-glucan, acacia fiber, pectin, wheat dextrin, cellulose, fructooligosaccharides, guar gum, fruit fiber, or combinations thereof. In some embodiments, the fiber is soluble dietary fiber.

[0150] In some embodiments, food products may contain protein. Protein may be present in a range of concentrations depending on the product. Protein sources may include soy protein, soy flour, soy protein isolate, whey protein isolate, casein, gelatin, legume protein isolate, soy protein concentrate, egg albumin or egg white, wheat protein concentrate, legume protein concentrate, and mixtures thereof. In some embodiments, meat products such as jerky, sausage, or meatballs may contain protein as a major ingredient. Protein may be present in concentrations ranging from about 10% to about 25% of the total ingredients. Dairy products such as cheese, yogurt, or milk may be primarily composed of proteins such as casein or whey. Protein may be present in concentrations ranging from about 3% to about 15% of the total ingredients. Plant-based products such as tofu, tempeh, or seitan may primarily contain proteins derived from soybeans, peas, legumes, or wheat. Protein may be present at a concentration ranging from about 10% to about 25% of the total ingredients. In energy and protein bars, proteins such as whey or soy, or any protein according to the present disclosure, may be added to provide a protein source. Protein may be present at a concentration ranging from about 10% to about 25% of the total ingredients. According to the present disclosure, the protein concentration may vary depending on the intended use of the product. In some embodiments, the protein may comprise from about 1% to about 95% by weight of the food product. In some embodiments, the protein may comprise from about 1% to about 95% by weight of the food product. In some embodiments, the food product may comprise about 1%, 3%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or a range having high and low values ​​independently selected from ranges including, between, and / or spanning the aforementioned values.

[0151] In some embodiments, the food product may include starch. In some embodiments, the food product may further include a starch component(s) in an amount sufficient to provide about 5% to 45%, or about 10% to 30%, or about 15% to 25% starch in the food product. The starch component may include purely added flour or other granules, as well as any starch fraction provided by other ingredients, such as oat bran or soy protein. In some embodiments, the starch may include any conventionally used starch or flour component for use in ready-to-eat cereals. Exemplary suitable starchy grains include flours from staple grains, including wheat, rice, corn (maize), oats, barley, and rye, or starch fractions isolated from cereal flours, including, for example, corn starch, wheat starch, rice starch, and various processed starches, including pregelatinized and / or modified starches.

[0152] In some embodiments, food products may contain wheat flour. According to the present disclosure, several types of wheat flour may be used. For example, common types of wheat flour used in food products include all-purpose flour (which, like other wheat flours, may contain protein), whole wheat flour, bread flour, cake flour, confectionery flour, self-rising flour, and gluten-free flour. According to the present disclosure, the concentration of wheat flour may vary depending on the intended use of the product. For example, in baked products such as bread, cake, and cookies, wheat flour is typically the primary ingredient and may be present at a concentration ranging from 50% to 100% of the total dry ingredients. In soups and sauces, wheat flour is often used as a thickener and may be present at a concentration ranging from 1% to 5% of the total ingredients. Batter and Breading: In fried foods such as chicken or fish, wheat flour is often used as part of the batter or breading and may be present at a concentration ranging from 20% to 50% of the total dry ingredients. In snack foods such as crackers and chips, wheat flour may be present at a concentration ranging from 30% to 70% of the total ingredients. In some embodiments, wheat flour may comprise from about 1% to about 95% by weight of the food product. In some embodiments, wheat flour may comprise from about 1% to about 95% by weight of the food product. In some embodiments, the food product may comprise wheat flour at about 1%, 3%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or a range with high and low values ​​independently selected from ranges including, between, and / or spanning the aforementioned values.

[0153] In some embodiments, the food product may include a fat. In some embodiments, the food product may include an oil. In some embodiments, the food product may include one or more fats or oils. Several types of fats may be used according to the present disclosure. For example, common types of fats include butter, margarine, vegetable oil, shortening, and lard. According to the present disclosure, the concentration of fat may vary depending on the intended use of the product. In baked goods such as cakes, cookies, and pastries, fats such as butter, shortening, or oil are often used to provide moisture, flavor, and texture. In some embodiments, fats may be included at a concentration ranging from 10% to 30% of the total ingredients. In some embodiments, fats such as olive oil or mayonnaise are often used to provide flavor and texture, as are sauces and dressings. In some embodiments, fats may be included at a concentration ranging from 10% to 30% of the total ingredients. In fried foods such as chicken or French fries, fats such as vegetable oil or lard are used for frying and may be included at a concentration ranging from 30% to 60% of the total ingredients. In snack foods such as chips and crackers, fats such as vegetable oils or palm oil are often used to provide flavor and texture. In some embodiments, fats may be present in concentrations ranging from 10% to 30% of the total ingredients. In some embodiments, fats may comprise from about 1% to about 95% by weight of the food product. In some embodiments, fats may comprise from about 1% to about 95% by weight of the food product. In some embodiments, fats may comprise from about 1%, 3%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or a range with high and low values ​​independently selected from ranges including, between, and / or spanning the aforementioned values.

[0154] In some embodiments, the food product may contain one or more additional ingredients. If desired, the disclosed food products may further contain various ingredients designed to enhance their aesthetic or nutritional qualities. These supplemental ingredients may include vitamin and / or mineral fortification, colorants, flavors, sweetener(s), and mixtures thereof. Exact ingredient concentrations may vary. However, generally, such ingredients may each comprise from about 0.01% to about 5%, or from about 0.1% to 2%, by dry weight of the food product. One particularly useful ingredient is common table salt. In some embodiments, the salt comprises from about 0.1% to 5%, or from about 0.5% to 4.0%, of the food product.

[0155] In some embodiments, the food product is derived from a plant. In some embodiments, the food product is derived from the husk of a hemp seed. In some embodiments, the food product is a solid food product. In some embodiments, the food product is a semi-solid food product. In some embodiments, the food product is a puffed product, a bakery product, a press cake, a ready-to-eat product, a food bar, a cereal, a crisp, or a spread.

[0156] Dietary supplements are orally ingested products containing the compounds or extracts disclosed herein and intended to supplement the diet. Dietary supplements are products derived from food sources that provide additional health benefits beyond the basic nutritional value contained in the food. Pharmaceutical compositions are defined as any component of a pharmaceutical product intended to provide pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or intended to affect the structure or any function of the human or other animal body. Dietary supplements, nutritional supplements, and pharmaceutical compositions can be found in many forms, such as capsules, tablets, coated tablets, pills, capsules, pellets, granules, soft gels, gel caps, liquids, powders, emulsions, suspensions, elixirs, syrups, and any other form suitable for use. In some embodiments, the compositions described herein are provided as dietary supplements. In some embodiments, dietary supplements are provided as capsules, tablets, powders, or in liquid form. In some embodiments, the compositions described herein are provided as nutritional supplements. In some embodiments, nutritional supplements are provided as capsules, tablets, powders, or in liquid form. In some embodiments, the compositions described herein are provided as a medicament, hi some embodiments, the medicament is provided as a capsule, tablet, powder, or in liquid form.

[0157] The pharmaceutical compositions disclosed herein may be prepared in a manner known per se, for example, by conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping, or tabletting processes. Further, the active ingredient is contained in an amount effective to achieve its intended purpose. Many of the compounds used in the pharmaceutical combinations disclosed herein may be provided as salts containing pharmaceutically compatible counterions.

[0158] Multiple techniques for administering compounds, salts, and / or compositions exist in the art, including, but not limited to, oral, rectal, pulmonary, topical, aerosol, injection, infusion, and parenteral delivery (including intramuscular, subcutaneous, intravenous, intramedullary, intrathecal, direct intraventricular, intraperitoneal, intranasal, and intraocular injection). In some embodiments, the compounds described herein, including pharmaceutically acceptable salts thereof, can be administered orally. In some embodiments, the compounds described herein, including compounds of Formula (I), (IA), (IB), (II), (III), or salts thereof, can be administered orally. In some embodiments, the compounds described herein, including compounds of Formula (I), (IA), (IB), (II), (III), or salts thereof, can be provided in a form for oral ingestion.

[0159] The compounds, salts and / or compositions may also be administered locally rather than systemically, for example, by injecting or implanting the compound directly into the affected area, often in a depot or sustained-release formulation. Furthermore, the compounds may be provided or administered in targeted drug delivery systems, for example, liposomes coated with tissue-specific antibodies. The liposomes are targeted to and selectively taken up by organs. For example, intranasal or pulmonary delivery may be desirable to target respiratory diseases or conditions.

[0160] Oral compositions may, if desired, be presented in a pack or dispenser device, which may contain one or more unit dosage forms containing the active ingredient. For example, the pack may comprise a metal or plastic flake, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. The pack or dispenser may also be in a form prescribed by a government agency regulating the manufacture, use, or sale of pharmaceuticals, with notice associated with the container, the notice reflecting the agency's approval of the drug dosage form for human or veterinary administration. Such notice may, for example, be labeling approved by the U.S. Food and Drug Administration for prescription drugs or an approved product insert. Compositions that may include the compounds and / or salts described herein formulated in a compatible pharmaceutical excipient may be prepared and placed in an appropriate container and labeled for treatment of an indicated condition.

[0161] The compounds, salts, and / or pharmaceutical compositions may be provided to the administering physician or other medical professional in the form of a kit. A kit is a package housing a container containing the compound(s) in a suitable pharmaceutical composition and instructions for administering the pharmaceutical composition to a subject. The kit may also optionally contain one or more additional therapeutic agents. The kit may also contain separate doses of the compound(s) or pharmaceutical composition for sequential or sequential administration. The kit may optionally contain one or more diagnostic tools and instructions for use. The kit may contain a suitable delivery device, such as a syringe, along with instructions for administering the compound(s) and any other therapeutic agents. The kit may optionally contain instructions for storage, reconstitution (if applicable), and administration of any or all included therapeutic agents. The kit may contain multiple containers reflecting the number of doses to be given to a subject.

[0162] In some embodiments, the oral compositions described herein are administered at a dose ranging from about 0.1 to 200 mg / kg body weight. In some embodiments, the oral compositions described herein are administered at a dose ranging from about 0.1 to 1, 0.5 to 1, 0.1 to 10, 0.5 to 10, 1 to 10, 1 to 20, 1 to 30, 1 to 40, 1 to 50, 1 to 60, 1 to 70, 1 to 80, 1 to 90, 1 to 100, 1 to 200, 1 to 300, 1 to 400, 1 to 500, 1 to 600, 1 to 700, 1 to 800, 1 to 900, 1 to 1000, 1 to 11, 1 to 12, 1 to 13, 1 to 14, 1 to 15, 1 to 16, 1 to 17, 1 to 18, 1 to 19, 10 to 20, 10 to 30, 10 to 40, 10 to 50, 10 to 60, 1 to 70, 1 to 80, 1 to 90, 1 to 1000, 1 to 11, 1 to 12, 1 to 13, 1 to 14, 1 to 15, 1 to 16, 1 to 17, 1 to 18, 1 to 19, 10 to 20, 10 to 30, 10 to 40, 10 to 50, 10 to 50, 10 to 60, 1 to 70, 1 to 80, 1 to 90, 1 to 1000, 1 to 11, 1 to 50, 10-60, 10-70, 10-80, 10-90, 10-100, 10-200, 10-300, 10-400, 10-500, 10-600, 10-700, 10-800, 10-900, 10-1000, 20-30, 20-40, 20-50, 20-60, 20-70, 20-80, 20-90, 20-100, 20-200, 20-300, 20-400, 20-500, 20-600, 20-700, 20-800, 20-900, 20-1000, 30-40, 30-50, 30-60, 30-70, 30-80, 30-90, 30-100, 30-200, 30-300, 30-400, 30-500, 30-600, 30-700, 30-800, 30-900, 30-1000, 40-50, 40-60, 40-70, 40-80, 40-90, 40-100, 40-200, 40-300, 40-400, 40-500, 40-600, 40-700, 40-800, 40-900, 40-1000, 50-60, 50-70, 50-80, 50-90, 50-100, 50-200, 50-300, 50-400 , 50~500, 50~600, 50~700, 50~800, 50~900, 60~70, 60~80, 60~90, 60~100, 60~200, 60~300, 60~400, 60~500, 60~600, 60~700, 60~800, 60~900, 60~1000, 70~80, 70~90, 70~100, 70~200, 70~300, 70~400, 70~500, 70~600, 70~700, 70~800, 70~900, 70~1000, 80~90, 80~100, 80~200, 80~300,It is administered at a dose within the range of 80-400, 80-500, 80-600, 80-700, 80-800, 80-900, 80-100, 90-100, 90-200, 90-300, 90-400, 90-500, 90-600, 90-700, 90-800, 90-900, 90-1000, 100-150, 100-200, 100-300, 100-400, 100-500, 100-600, 100-700, 100-800, 100-900, or 100-1000 mg / kg body weight. In some embodiments, the oral compositions described herein contain at least about 0.01, 0.02, 0.03, 0.05, 0.07, 0.1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 0.5, 19, 19.5, 20, 20.5, 21, 21.5, 22, 22.5, 23, 23.5, 24, 24.5, 25, 25.5, 26, 26.5, 27, 27.5, 28, 28.5, 29, 29.5, 30, 30.5, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 55, 60, 65, 70, 80, 90, or 95 mg / kg body weight. In some embodiments, the oral compositions described herein contain about 0.01, 0.02, 0.03, 0.05, 0.07, 0.1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 4.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, 20, 20.5, 21, 21.5, 22, 22.5, 23, 23.5, 24, 24.5 , 25, 25.5, 26, 26.5, 27, 27.5, 28, 28.5, 29, 29.5, 30, 30.5, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40mg / m, 2In some embodiments, the oral compositions described herein are administered in a dose of about 0.01, 0.02, 0.03, 0.05, 0.07, 0.1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, and administered at doses exceeding 9.5, 20, 20.5, 21, 21.5, 22, 22.5, 23, 23.5, 24, 24.5, 25, 25.5, 26, 26.5, 27, 27.5, 28, 28.5, 29, 29.5, 30, 30.5, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 mg / kg of subject body weight.

[0163] In some embodiments, the dose of the oral compositions described herein is about 0.1 mg to 10 mg, 0.1 mg to 25 mg, 0.1 mg to 30 mg, 0.1 mg to 50 mg, 0.1 mg to 75 mg, 0.1 mg to 100 mg, 0.5 mg to 10 mg, 0.5 mg to 25 mg, 0.5 mg to 30 mg, 0.5 mg to 50 mg, 0.5 mg to 75 mg, 0.5 mg to 100 mg, 1 mg to 10 mg, 1 mg to 1 mg~25mg, 1mg~30mg, 1mg~50mg, 1mg~75mg, 1mg~100mg, 2mg~10mg, 2mg~25mg, 2mg~30mg, 2mg~50mg, 2mg~75mg, 2mg~100mg, 3mg~10mg, 3mg~25mg, 3mg~30mg, 3mg~50mg, 3mg~75mg, 3mg~100mg, 4mg~100mg, 5mg~10mg, 5mg~25 mg, 5mg~30mg, 5mg~50mg, 5mg~75mg, 5mg~300mg, 5mg~200mg, 7.5mg~15mg, 7.5mg~25mg, 7.5mg~30mg, 7.5mg~5 0mg, 7.5mg~75mg, 7.5mg~100mg, 7.5mg~200mg, 10mg~20mg, 10mg~25mg, 10mg~50mg, 10mg~75mg, 10mg~100mg, 15mg to 30mg, 15mg to 50mg, 15mg to 100mg, 20mg to 20mg, 20mg to 100mg, 30mg to 100mg, 40mg to 100mg, 10mg to 80mg, 15mg to 80mg, 20mg to 80mg, 30mg to 80mg, 40mg to 80mg, 10mg to 60mg, 15mg to 60mg, 20mg to 60mg, 30mg to 60mg, or about 40mg to 60mg. In some embodiments, the oral compositions described herein contain between about 1 mg and 5 mg, 1 mg and 7.5 mg, 2.5 mg and 5 mg, 2.5 mg and 7.5 mg, 5 mg and 7.5 mg, 5 mg and 9 mg, 5 mg and 10 mg, 5 mg and 12 mg, 5 mg and 14 mg, 5 mg and 15 mg, 5 mg and 16 mg, 5 mg and 18 mg, 5 mg and 20 mg, 5 mg and 22 mg, 5 mg and 24 mg, 5 mg and 26 mg, 5 mg and 28 mg, 5 mg and 30 mg, 5 mg and 32 mg, 5 mg and 34 mg, 5 mg and 36 mg, 5 mg and 38 mg, 5 mg and 40 mg, 5 mg and 42 mg, 5 mg and 44 mg, 5 mg and 46 mg, 5 mg and 48 mg,5mg~50mg、5mg~52mg、5mg~54mg、5mg~56mg、5mg~58mg、5mg~60mg、7mg~7.7mg、7mg~9mg、7mg~10mg、7mg~12mg、7mg~14mg、7mg~15mg、7mg~16mg、7mg~18mg、7mg~20mg、7mg~22mg、7mg~24mg、7mg~26mg、7mg~28mg、7mg~30mg、7mg~32mg、7mg~34mg、7mg~36mg、7mg~38mg、7mg~40mg、7mg~42mg、7mg~44mg、7mg~46mg、7mg~48mg、7mg~50mg、7mg~52mg、7mg~54mg、7mg~56mg、7mg~58mg、7mg~60mg、9mg~10mg、9mg~12mg、9mg~14mg、9mg~15mg、9mg~16mg、9mg~18mg、9mg~20mg、9mg~22mg、9mg~24mg、9mg~26mg、9mg~28mg、9mg~30mg、9mg~32mg、9mg~34mg、9mg~36mg、9mg~38mg、9mg~40mg、9mg~42mg、9mg~44mg、9mg~46mg、9mg~48mg、9mg~50mg、9mg~52mg、9mg~54mg、9mg~56mg、9mg~58mg、9mg~60mg、10mg~12mg、10mg~14mg、10mg~15mg、10mg~16mg、10mg~18mg、10mg~20mg、10mg~22mg、10mg~24mg、10mg~26mg、10mg~28mg、10mg~30mg、10mg~32mg、10mg~34mg、10mg~36mg、10mg~38mg、10mg~40mg、10mg~42mg、10mg~44mg、10mg~46mg、10mg~48mg、10mg~50mg、10mg~52mg、10mg~54mg、10mg~56mg、10mg~58mg、10mg~60mg、12mg~14mg、12mg~15mg、12mg~16mg、12mg~18mg、12mg~20mg、12mg~22mg、12mg~24mg、12mg~26mg、12mg~28mg、12mg~30mg、12mg~32mg、12mg~34mg、12mg~36mg、12mg~38mg、12mg~40mg、12mg~42mg、12mg~44mg、12mg~46mg、12mg~48mg、12mg~50mg、12mg~52mg、12mg~54mg、12mg~56mg、12mg~58mg、12mg~60mg、15mg~16mg、15mg~18mg、15mg~20mg、15mg~22mg、15mg~24mg、15mg~26mg、15mg~28mg、15mg~30mg、15mg~32mg、15mg~34mg、15mg~36mg、15mg~38mg、15mg~40mg、15mg~42mg、15mg~44mg、15mg~46mg、15mg~48mg、15mg~50mg、15mg~52mg、15mg~54mg、15mg~56mg、15mg~58mg、15mg~60mg、17mg~18mg、17mg~20mg、17mg~22mg、17mg~24mg、17mg~26mg、17mg~28mg、17mg~30mg、17mg~32mg、17mg~34mg、17mg~36mg、17mg~38mg、17mg~40mg、17mg~42mg、17mg~44mg、17mg~46mg、17mg~48mg、17mg~50mg、17mg~52mg、17mg~54mg、17mg~56mg、17mg~58mg、17mg~60mg、20mg~22mg、20mg~24mg、20mg~26mg、20mg~28mg、20mg~30mg、20mg~32mg、20mg~34mg、20mg~36mg、20mg~38mg、20mg~40mg、20mg~42mg、20mg~44mg、20mg~46mg、20mg~48mg、20mg~50mg、20mg~52mg、20mg~54mg、20mg~56mg、20mg~58mg、20mg~60mg、22mg~24mg、22mg~26mg、22mg~28mg、22mg~30mg、22mg~32mg、22mg~34mg、22mg~36mg、22mg~38mg、22mg~40mg、22mg~42mg、22mg~44mg、22mg~46mg、22mg~48mg、22mg~50mg、22mg~52mg、22mg~54mg、22mg~56mg、22mg~58mg、22mg~60mg、25mg~26mg、25mg~28mg、25mg~30mg、25mg~32mg、25mg~34mg、25mg~36mg、25mg~38mg、25mg~40mg、25mg~42mg、25mg~44mg、25mg~46mg、25mg~48mg、25mg~50mg、25mg~52mg、25mg~54mg、25mg~56mg、25mg~58mg、25mg~60mg、27mg~28mg、27mg~30mg、27mg~32mg、27mg~34mg、27mg~36mg、27mg~38mg、27mg~40mg、27mg~42mg、27mg~44mg、27mg~46mg、27mg~48mg、27mg~50mg、27mg~52mg、27mg~54mg、27mg~56mg、27mg~58mg、27mg~60mg、30mg~32mg、30mg~34mg、30mg~36mg、30mg~38mg、30mg~40mg、30mg~42mg、30mg~44mg、30mg~46mg、30mg~48mg、30mg~50mg、30mg~52mg、30mg~54mg、30mg~56mg、30mg~58mg、30mg~60mg、33mg~34mg、33mg~36mg、33mg~38mg、33mg~40mg、33mg~42mg、33mg~44mg、33mg~46mg、33mg~48mg、33mg~50mg、33mg~52mg、33mg~54mg、33mg~56mg、33mg~58mg、33mg~60mg、36mg~38mg、36mg~40mg、36mg~42mg、36mg~44mg、36mg~46mg、36mg~48mg、36mg~50mg、36mg~52mg、36mg~54mg、36mg~56mg、36mg~58mg、36mg~60mg、40mg~42mg、40mg~44mg、40mg~46mg、40mg~48mg、40mg~50mg、40mg~52mg、40mg~54mg、40mg~56mg、40mg~58mg、40mg~60mg、43mg~46mg、43mg~48mg、43mg~50mg、43mg~52mg、43mg~54mg、43mg~56mg、43mg~58mg、42mg~60mg、45mg~48mg、45mg~50mg、45mg~52mg、45mg~54mg、45mg~56mg、45mg~58mg、45mg~60mg、48mg~50mg、48mg~52mg、48mg~54mg、48mg~56mg、48mg~58mg、48mg~60mg、50mg~52mg、50mg~54mg、It is administered at 50 mg to 56 mg, 50 mg to 58 mg, 50 mg to 60 mg, 52 mg to 54 mg, 52 mg to 56 mg, 52 mg to 58 mg, or 52 mg to 60 mg. In some embodiments, the dose of the oral compositions described herein is about 0.1 mg, 0.3 mg, 0.5 mg, 0.75 mg, 1 mg, 1.25 mg, 1.5 mg, 1.75 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 5 mg, about 10 mg, about 12.5 mg, about 13.5 mg, about 15 mg, about 17.5 mg, about 20 mg, about 22.5 mg, about 25 mg, about 27 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 125 mg, about 150 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, or about 1000 mg or more. In some embodiments, the dose of the oral compositions described herein is less than about 0.5 mg, 0.75 mg, 1 mg, 1.25 mg, 1.5 mg, 1.75 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 5 mg, about 10 mg, about 12.5 mg, about 13.5 mg, about 15 mg, about 17.5 mg, about 20 mg, about 22.5 mg, about 25 mg, about 27 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 125 mg, about 150 mg, or about 200 mg.

[0164] When preparing solid compositions such as tablets or capsules, the compound or extract is mixed with carriers (e.g., conventional tableting ingredients such as corn starch, lactose, sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicalcium phosphate, or gums) and other diluents (e.g., water) to form a solid composition. This solid composition is then subdivided into unit dosage forms containing an effective amount of a compound of the present disclosure. Tablets or pills containing the compound or extract can be coated or otherwise compounded to provide a dosage form offering the advantage of prolonged action.

[0165] The liquid forms that the compounds or extracts of the present disclosure are formulated for oral or parenteral administration include aqueous solutions, suitably flavored syrups, aqueous or oily suspensions, flavored emulsions with edible oils, and elixirs and similar vehicles.Suitable dispersants or suspending agents for aqueous suspensions include synthetic natural gums, such as tragacanth, acacia, alginate, dextran, sodium carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone, or gelatin.The liquid preparations for oral administration can be, for example, in the form of solution, syrup, or suspension, or they can be presented as dry products that are to be reconstituted with water or other suitable vehicles before use. Such liquid preparations may be prepared by conventional means with acceptable additives such as suspending agents (e.g., sorbitol syrup, methylcellulose, or edible hydrogenated oils); emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters, or ethyl alcohol); preservatives (e.g., methyl or propyl p-hydroxybenzoate, or sorbic acid); and artificial or natural colorants and / or sweeteners.

[0166] Methods for preparing the formulations or compositions of the present disclosure include the step of bringing the disclosed compounds or extracts into association with the carriers and, optionally, one or more accessory ingredients and / or active ingredients. Generally, the formulations are prepared by uniformly and intimately bringing the disclosed compounds or extracts into association with liquid carriers, or finely divided solid carriers, or both, and then, if necessary, shaping the product. Thus, the disclosed formulations may consist of, or consist essentially of, the compounds or extracts described herein in combination with suitable carriers.

[0167] When administered to humans or animals as a pharmaceutical, nutraceutical, or dietary supplement, the compounds or extracts of the present disclosure can be administered per se or as a composition containing, for example, 0.1-99% of the active ingredient in combination with an acceptable carrier. In some embodiments, one or more compounds or extracts of the present disclosure can be administered at about 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% w / w, or a range including and / or spanning the aforementioned values.

[0168] In some embodiments, the enriched food, dietary supplement, or medical food may further comprise one or more of proteins, carbohydrates, and / or fats used by the body, preferably the human body, to maintain growth, repair, and vital processes and to provide energy. When provided as an enriched food, dietary supplement, or medical food, the composition comprises selected compounds, compositions, or extracts of the present disclosure, so that they can be ingested simultaneously with or about simultaneously with food. In some embodiments, the enriched food, dietary supplement, or medical food is generally ingested within about 1 hour before or after eating food. In some embodiments, the enriched food, dietary supplement, or medical food is generally ingested within about 15 minutes before or after eating food. In some embodiments, the enriched food, dietary supplement, or medical food is generally ingested within about 5 minutes before or after eating food. In some embodiments, the dietary supplement or nutritional supplement can also be ingested simultaneously with food or together with the enriched food, dietary supplement, or medical food.

[0169] Methods and Uses In some embodiments, the present disclosure provides methods and uses for improving, restoring, regulating, or maintaining sleep. According to such methods, an effective amount of one or more compounds or compositions of the present disclosure is provided to a subject in need thereof to improve, restore, regulate, or maintain the subject's sleep. As used herein, the term "subject" refers to an animal, preferably a mammal. In some embodiments, the subject is a veterinary, companion animal, livestock, laboratory animal, or zoo animal. In other embodiments, the subject is a human.

[0170] Several signaling molecules have been identified that play a role in sleep. Various neurotransmitters, including noradrenaline, acetylcholine, histamine, dopamine, serotonin, and the neuropeptides orexin A and B (also called hypocretin), promote wakefulness. Orexin is a neuropeptide involved in regulating the sleep-wake cycle, feeding patterns, energy balance, and stress in mammals. Dysregulation or loss of orexin signaling is associated with narcolepsy. In some embodiments, the plant extracts or compounds described herein are orexin receptor antagonists. In some embodiments, the plant extracts or compounds described herein include orexin receptor 2 (OX2) antagonists. In some embodiments, the plant extracts or compounds described herein include orexin receptor 1 (OX1) antagonists. In some embodiments, the plant extracts or compounds described herein can be antagonists of both orexin receptor 1 and orexin receptor 2. In some embodiments, the compounds or compositions described herein may be useful in methods of antagonizing orexin receptor activity in a subject in need of such inhibition, comprising administering an effective amount of the compound. The utility of the compounds of the present disclosure as antagonists of OX1 and / or OX2 was demonstrated by the FLIPR Ca 2+This may be readily determined without undue experimentation by methods known in the art, including the "Flux Assay" (Okumura et al., Biochem. Biophys. Res. Comm. 280:976-981, 2001).

[0171] Calcium influx may be important for generating on / off state cycling and REM sleep. In some embodiments, the plant extracts or compounds described herein provide for a reduction in calcium influx in a subject. In some embodiments, a method for reducing calcium influx in a subject comprises administering a composition described herein to the subject.

[0172] Sleep deprivation leads to ER stress and activation of the endoplasmic reticulum kinase (pERK) pathway. In some embodiments, the plant extracts or compounds described herein result in a decrease in the phosphorylation of pERK1 / 2. In some embodiments, a method for inactivating pERK1 / 2 phosphorylation in a subject comprises administering a composition provided herein.

[0173] In some embodiments, the method includes rapidly inducing sleep in a subject by administering a composition described herein, in some embodiments, the subject falls asleep more rapidly than about 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 15.0%, 20%, 25%, 50.0%, 75.0%, or ranges inclusive and / or spanning the foregoing values.

[0174] In some embodiments, the method includes promoting good quality sleep in a subject by administering a composition described herein, in some embodiments, the subject's sleep quality is improved by about 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 15.0%, 20%, 25.0%, 50.0%, 75.0%, or ranges inclusive and / or spanning the foregoing values.

[0175] In some embodiments, the method includes providing productive sleep in a subject by administering a composition described herein, in some embodiments, the subject's productive sleep improves by about 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 15.0%, 20%, 25.0%, 50.0%, 75.0%, or a range inclusive and / or spanning the foregoing values.

[0176] In some embodiments, the method includes providing a subject with a full night's sleep by administering a composition described herein. In some embodiments, the subject sleeps, on average, about 15 minutes, 30 minutes, 45 minutes, 60 minutes, 75 minutes, 90 minutes, 105 minutes, 120 minutes, 135 minutes, 150 minutes, 165 minutes, 180 minutes longer, or ranges inclusive and / or spanning the foregoing values. In some embodiments, the method includes reducing the time it takes to fall asleep in the subject by administering a composition described herein. In some embodiments, the subject reduces the time it takes to fall asleep by about 15 minutes, 30 minutes, 45 minutes, 60 minutes, 75 minutes, 90 minutes, 105 minutes, 120 minutes, 135 minutes, 150 minutes, 165 minutes, 180 minutes longer, or ranges inclusive and / or spanning the foregoing values.

[0177] In some embodiments, the method includes increasing slow-wave sleep 1-4 in a subject by administering a composition described herein. In some embodiments, the method includes increasing REM sleep in a subject by administering a composition described herein. In some embodiments, the method includes increasing deep sleep in a subject by administering a composition described herein. Humans experience various sleep periods. These include slow-wave sleep 1 (SWS1), slow-wave sleep 2 (SWS2), slow-wave sleep 3 (SWS3), slow-wave sleep 4 (SWS4), and rapid eye movement (REM). SWS1 and SWS2 are both periods of light sleep from which it is relatively easy to wake a person. Light sleep typically occurs in the second half of sleep. SWS3 and SWS4 are both periods of deep sleep, which are difficult to awaken a sleeper. Deep sleep typically occurs in the first half of sleep, and each subsequent period becomes shorter. REM sleep is the sleep period in which a person experiences their most vivid dreams. The wave patterns resemble those seen when a person is awake. In healthy individuals, SWS1 accounts for about 5% of sleep, SWS2 accounts for about 50% of sleep, SWS3 accounts for about 10% of sleep, SWS4 accounts for about 10% of sleep, and REM accounts for about 25% of sleep. In some embodiments, the methods may increase slow-wave sleep 1 by about 1% to about 5% of the subject's sleep. In some embodiments, the methods may increase slow-wave sleep 2 by about 10% to about 50% of the subject's sleep. In some embodiments, the methods may increase slow-wave sleep 3 by about 2% to about 10% of the subject's sleep. In some embodiments, the methods may increase slow-wave sleep 4 by about 2% to about 10% of the subject's sleep. In some embodiments, the methods may increase REM by about 10% to about 25% of the subject's sleep.

[0178] In some embodiments, the method improves sleep disorders in a subject by administering a composition described herein to the subject. Sleep disorders are described in the International Classification of Sleep Disorders (ICDS). ICDS-3 was published in 2014 and characterizes sleep disorders as belonging to one of the following classes: (1) insomnia; (2) sleep-related breathing disorders; (3) central disorders of excessive sleepiness; (3) circadian rhythm sleep-wake disorders; (4) parasomnia; and (5) sleep-related movement disorders. Therefore, sleep disorders that can be treated by the oral compositions described herein include sleep disorders in the following classes: (1) insomnia; (2) sleep-related breathing disorders; (3) central disorders of excessive sleepiness; (3) circadian rhythm sleep-wake disorders; (4) parasomnia; and (5) sleep-related movement disorders. In particular, the oral composition may be effective in treating a sleep disorder selected from insomnia, narcolepsy, hypersomnia, sleep apnea syndrome, periodic limb movement disorder, restless legs syndrome, nighttime eating (and drinking) syndrome, jet lag, shift work sleep disorder, irregular sleep-wake patterns, confusional awakenings, sleepwalking, sleep terrors, sleep talking, nightmares, sleep paralysis, REM sleep behavior disorder, snoring, sleeping sickness, sleep disorders associated with other diseases or conditions, or other sleep disorders.

[0179] An "effective amount" refers to an amount that, when administered to a patient, provides a sufficient amount of drug to achieve an effect. In the case of a treatment method, this effect may be treatment of a sleep disorder. Thus, an "effective amount" may also be a "therapeutically effective amount." A "therapeutically effective amount" refers to an amount that, when administered to a subject, provides a sufficient amount of drug to treat a disease or a symptom of a disease.

[0180] As used herein, the terms "treating," "treatment," "treat," and the like refer to affecting a subject, tissue, or cell to achieve a desired pharmacological and / or physiological effect. The effect may be preventative, in that it completely or partially prevents or reduces the severity of a disease or associated symptoms, or therapeutic, in that it partially or completely cures a disease. Thus, for example, reference to "treating" a sleep disorder encompasses (a) helping a subject fall asleep; (b) helping a subject stay asleep after sleep is achieved; c) alleviating or reducing the effects of the sleep disorder, e.g., enhancing wakefulness during non-sleep periods; or (d) preventing a sleep disorder from occurring in a subject predisposed to or at risk for a sleep disorder, so that the sleep disorder does not occur in the subject, or if it does occur, it occurs in a less severe form.

[0181] In some embodiments, a method for treating insomnia in a subject comprises administering one or more compounds described herein. In some embodiments, a method for treating insomnia in a subject comprises administering an oral composition described herein. Symptoms and severity of insomnia may be measured using the Insomnia Severity Index (ISI) questionnaire. Typically, the ISI is administered by a clinician, nurse, or researcher, or may be self-administered by the patient. The ISI assesses both the nighttime and daytime components of insomnia and is available in multiple languages. The ISI asks patients to rate seven questions, each on a scale of 0 to 4, regarding (1) difficulty falling asleep, (2) difficulty maintaining sleep, (3) problems waking up early, (4) satisfaction with their current sleep pattern, (5) perception of how noticeable their sleep problem is to others, (6) level of concern about their sleep problem, and (7) how much their sleep problem interferes with daily life. The method may result in improvement in one or more of these seven aspects of insomnia. In some embodiments of the methods of treatment, the subject being treated may have an initial ISI score of 7 or greater, and in some cases, the initial ISI score may be 10 or greater. In some embodiments, the methods of treating insomnia may result in a decrease in the patient's ISI score compared to the initial ISI score. This decrease in ISI score may be 1, 2, 3, 4, 5, 6 or more units on the ISI scale, and preferably, the patient's ISI score after treatment is 7 or less.

[0182] The ISI may be used alone to assess the severity of a subject's insomnia, or may be used in conjunction with one or more other questionnaires, such as the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-les-Q), the Work and Social Adjustment Scale (WSAS), the Depression, Anxiety, and Stress Scale (DASS) questionnaire, the Dysfunctional Beliefs About Sleep (DBAS) questionnaire, the Multidimensional Fatigue Inventory questionnaire, and other known questionnaires known in the art.

[0183] Typically, patients are assessed with one or more questionnaires before receiving treatment and then at regular intervals throughout treatment (e.g., at 1, 2, 3, 4, 5, 6, 7, or 8 week intervals). On-treatment assessments may begin as early as 2 weeks after initiation of treatment.

[0184] In some embodiments, treatment may be maintained for up to 14 days, for example, treatment may be maintained for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 days. In some embodiments, treatment is maintained for longer than 14 days, for example, 3 weeks, 1, 2, 3, 4, 5, 6, 12, 18, 24, 36 months or longer.

[0185] Typically, the oral composition is administered once a day, preferably immediately before the patient attempts to go to sleep. In some embodiments, the oral composition is administered within about 2 hours after the patient attempts to go to sleep, for example, within about 1.5 hours, within about 1 hour, or within about 30 minutes before sleep.

[0186] In some embodiments, insomnia may be assessed by measuring one or more objective measures of sleep. Objective measures of sleep may be measured by polysomnography (PSG) and / or activity measurement. Objective measures of sleep may include measuring sleep onset latency (SO); wake after sleep onset (WASO); total sleep time (TST); sleep efficiency (SE); the proportion of time spent in REM sleep and all sleep stages compared to non-REM sleep patterns, including slow-wave sleep patterns; sleep apnea; periodic limb movements; and combinations thereof. In some embodiments, a method for treating insomnia may provide an improvement in one or more objective measures of sleep, for example, two, three, four, five, six, or more objective measures of sleep.

[0187] In some embodiments, the compounds or compositions of the present disclosure may be administered in combination with other compounds to improve sleep quality, hi some embodiments, the compounds or compositions of the present disclosure may be administered in combination with other compounds to treat or prevent sleep disorders and sleep disturbances. In some embodiments, the other compounds include sedatives, hypnotics, anxiolytics, antipsychotics, anxiolytics, antihistamines, benzodiazepines, barbiturates, cyclopyrrolones, GABA agonists, 5HT-2 antagonists including 5HT-2A antagonists and 5HT-2A / 2C antagonists, histamine H3 antagonists, histamine antagonists including histamine H3 inverse agonists, imidazopyridines, mild tranquilizers, melatonin agonists and antagonists, melatonin agonists, prokinetin agonists and antagonists, pyrazolopyrimidines, T-type calcium channel antagonists, triazolopyridines, such as, for example, adinazolam, allobarbital, alonimideAlprazolam, amitriptyline, amobarbital, amoxapine, armodafinil, APD-125, bentazepam, benzoctamine, brotizolam, bupropion, busprion, butabarbital, capromorelin, capride, carbochloral, chloral betaine, chloral hydrate, chlordiazepoxide, clomipramine, clonazepam, cloperidone, clorazepate, chloresate, clozapine, conazepam, ciprazepam, desipramine, dexclamol, diazepam, dichloralphenazone , divalproex, diphenhydramine, doxepin, EMD-281014, eplivanserin, estazolam, eszopiclone, esclorinol, etomidate, fenobam, flunitrazepam, flurazepam, fluvoxamine, fluoxetine, fosazepam, gaboxadol, glutethimide, halazepam, hydroxyzine, ibutamoren, imipramine, indiplon, lithium, lorazepam, lormetazepam, LY-156735, maprotiline, MDL-100907, mecloqualone, melatonin, mefonazepam Ibuprofen, meprobamate, methaqualone, methyprylon, midaflur, midazolam, modafinil, nefazodone, NGD-2-73, nisobamate, nitrazepam, nortriptyline, ornortriptyline, oxazepam, paraldehyde, paroxetine, pentobarbital, perlapine, perphenazine, phenelzine, phenobarbital, prazepam, promethazine, propofol, protriptyline, quazepam, ramelteon, liclazepam, loretamide, secobarbital, sertraline, sprox The therapeutic agents that may be used include, but are not limited to, thiazolinone, TAK-375, temazepam, thioridazine, tiagabine, tracazolate, tranylcypromine, trazodone, triazolam, trepipam, tricetamide, triclofos, trifluoperazine, trimetozine, trimipramine, urdazepam, venlafaxine, zaleplon, zolazepam, zopiclone, zolpidem, and salts thereof, and combinations thereof, or the compounds of the present invention may be administered in conjunction with the use of physical methods such as light therapy and electrical stimulation.

[0188] The present disclosure also provides methods and uses for treating, improving, restoring, regulating, or maintaining the body weight of a subject. According to such methods, an effective amount of one or more compounds or compositions of the present disclosure is provided to a subject in need thereof to treat, improve, restore, regulate, or maintain the body weight of the subject. In some embodiments, the one or more compounds, plant extracts, or compositions are present in an amount sufficient to promote health and wellness.

[0189] In some embodiments, methods for weight management in a subject include administering one or more compounds or compositions described herein to the subject. In some embodiments, the subject loses and / or maintains weight. In some embodiments, weight is lost and / or maintained by about 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 15.0%, 20%, or a range inclusive and / or spanning the foregoing values ​​from the subject's original weight.

[0190] In some embodiments, a method for appetite suppression comprises administering to a subject a composition described herein, in which the subject feels fuller by about 1.0%, about 2.0%, about 3.0%, about 4.0%, about 5.0%, about 6.0%, about 7.0%, about 8.0%, about 9.0%, about 10.0%, about 15.0%, about 20%, or ranges inclusive and / or spanning the foregoing values ​​after administration of one or more compounds or compositions described herein.

[0191] In some embodiments, a method for suppressing appetite in a subject comprises administering a composition described herein to the subject, in some embodiments, the subject's appetite is reduced by about 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 15.0%, 20%, or a range including and / or spanning the foregoing values ​​after administration of one or more compounds or compositions described herein.

[0192] In some embodiments, a method for inducing satiety in a subject comprises administering a composition described herein to the subject. In some embodiments, the induced satiety in the subject increases by about 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 15.0%, 20%, or a range including and / or spanning the aforementioned values ​​after administration of one or more compounds or compositions described herein. Satiety and / or satiety can be assessed using consumer surveys (e.g., human subjects) that can demonstrate statistically significant measures of increased satiety and / or satiety.

[0193] Also provided are methods for promoting weight loss by administering a composition provided herein to a subject. In some embodiments, the subject loses weight by about 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 15.0%, 20%, or a range inclusive and / or spanning the aforementioned values ​​after administration of one or more compounds or compositions described herein. The amount and duration of such administration will depend on the individual's weight loss needs and health status and can be assessed by one skilled in the art. The subject's weight loss can be measured over time to determine whether weight loss is occurring. Weight loss can be compared to control animals not administered the ingestible composition. [Example]

[0194] The following non-limiting examples are provided to further illustrate the present disclosure. Example 1 A Dionex™ Accelerated Solvent Extractor 350 was used to extract plant material. Four 100 mL stainless steel ASE extraction cells were filled with 25 g of ground plant tissue. The preset temperature was 60°C, and static extraction was performed for a total of 12 extraction cycles. The solvents used for extraction were 95% ethanol, ethyl acetate, and hexane. The solvent was removed, and the 95% ethanol extract was subjected to a bioassay-guided fractionation protocol. Briefly, the extract was dry-loaded onto a C18 spherical flash column. Elution was performed at a flow rate of 30 mL / min using a mobile phase consisting of water + 0.1% formic acid (A) and CH3CN + 0.1% formic acid (B), following a gradient from 1% to 3% B in 3 min, increasing to 100% B in 22 min, and then maintaining 100% B for 7 min. Highly active fractions were pooled and the pooled sample was further purified by bioassay-guided fractionation using a Kinetex reversed-phase C18 preparative column to yield costunolide.

[0195] Example 2 This is a prophetic example. In this example, the plant tissues in Table 1 were extracted using the extraction method of Example 1. [Table 2-1] [Table 2-2]

[0196] The amount of costunolide or other compounds of interest, such as those described herein, present in a particular extract (% extract, w / w) is determined. Quantitation of the compounds is performed by normalizing the results by the weight of the extract. The results of these analyses are interpreted.

[0197] Example 3 The oral composition is provided daily after which the patient goes to bed with the intention of getting a good night's rest, and utilizes a caplet formulation containing an extract of Eupatorium perfoliatum and a carrier.

[0198] Directions: For the oral composition, take one capsule orally once daily with a glass of water (8 ounces) before bedtime. Preferably, the oral composition is taken with the intention of achieving a good night's sleep.

[0199] Example 4 In this example, the in vitro biological activity of naturally occurring compounds derived from plants described herein was investigated to determine whether they can modulate orexin receptors. Structures 20-38 were identified as modulating orexin receptors (Orx1, Orx2) or both. Figures 1-11 show compounds 20-30 as modulating Orx2 agonists. Figure 12 shows compounds 31-38 as modulating orexin receptor (Orx1, Orx2) agonists.

[0200] Example 5 In this example, the in vitro biological activity of naturally occurring compounds was evaluated.

[0201] In this example, the following protocol was used: 1.) Seed cells in 20 μL of cell seeding reagent; 2.) Incubate cells overnight at 37°C, 5% CO2; 3.) Treat cells with 2.5 μL of 10X antagonist prepared in compound dilution buffer (for OR2 screening, add 2.5 μL of 1:100 natural product sample to DiscoverX cell seeding reagent. A 10X stock of the control antagonist, Seltrexant, was prepared at 1500 nM); 4.) Incubate for 30 minutes at 37°C, 5% CO2; 5.) Treat cells with 2.5 μL of 10X agonist prepared in compound dilution buffer (for OR2 screening, add 2.5 μL of 10X orexin BEC80, 252.7 nM); 6.) Incubate for 90 minutes at 37°C, 5% CO2; 7.) Add 12.5 μL of working detection solution. 8.) Incubate in the dark at room temperature for 1 hour, and 9.) Read the chemiluminescent signal.

[0202] The plants described herein were tested to determine the concentration (μM) required to achieve the relative IC50 of the OR2 receptor, the absolute percent agonism achieved at the μM concentration of the relative OR2 IC50, the percentage of receptor activity at the concentration (μM) required to achieve the OR2 IC50, cell viability as measured by XTT assay at the IC50 μM concentration, the concentration (fold dilution) of fractions required to achieve the OR2 IC50, and the percentage of receptor activity at the concentration (fold dilution) of fractions required to achieve the OR2 IC50. The results are listed in Table 2. [Table 3]

[0203] Example 6 In this example, the in vivo tolerability of compounds 26, 21, 29, and 13 was evaluated.

[0204] Experimentally naive male Sprague-Dawley rats were acclimated to the treatment room in their own cages for up to 7 days after arrival at the testing facility, with free access to food and water. On the day of the experiment, animals were allowed to acclimate to the experimental room for at least 1 hour before the start of any experiments. All animals were tail-marked, weighed, and randomly assigned to treatment groups. Animals (n=3 per dose) were treated with either Compounds 26, 21, 29, or 13 (10 mL / kg, PO). Up to four doses of each compound were tested using a dose-escalation procedure starting at 30 mg / kg. If this initial dose was well tolerated, the dose was increased to 100 mg / kg. If the 30 mg / kg dose was not tolerated, the dose was reduced to 15 mg / kg. Following the dose-escalation procedure, if the 100 mg / kg dose was well tolerated, the dose was increased to 315 mg / kg. If not tolerated, the dose is reduced to 60 mg / kg. This pattern continues with the following decision points: if 315 mg / kg is well tolerated, the dose is increased to a maximum of 500 mg / kg. If 315 mg / kg is not tolerated, the dose is reduced to 200 mg / kg. After compound administration, each animal was placed in a clear Perspex cage and observed for 60 minutes, of which recordings were taken at 15, 30, and 60 minutes.

[0205] Compound 26 was supplied by Arctom as a yellow powder. For formulation, a vehicle of 10% dimethyl sulfoxide (DMSO) in 20% hydroxypropyl beta-cyclodextrin (HPBC) was used. The dose escalation procedure involved a dose volume of 10 mL / kg based on an assumed body weight of 300 grams per animal. This resulted in a dose volume of approximately 3 mL per animal. With three animals per group, the total dose volume required per group was 9 mL. Four dose concentrations were prepared: for the 30 mg / kg dose concentration, 45 mg of Compound 26 was weighed and dissolved in a total volume of 15 mL (1.5 mL DMSO + 13.5 mL 20% HPBC). After weighing, Compound 26 was dissolved in the calculated volume of vehicle. To ensure proper mixing and dissolution, the solution was sonicated, resulting in a yellow, milky solution. Similar procedures were followed for the other doses.

[0206] Compound 26 was supplied as a yellow powder by Brightseed Inc. For formulation, a vehicle of 10% dimethyl sulfoxide (DMSO) in 20% hydroxypropyl beta-cyclodextrin (HPBC) was used. Four dose concentrations were prepared: for the 30 mg / kg dose concentration, 45 mg of tiliroside was weighed and dissolved in a total volume of 15 mL (1.5 mL of DMSO + 13.5 mL of 20% HPBC). To ensure proper mixing and dissolution, the solution was sonicated, resulting in a yellow, milky solution. Similar procedures were followed for the other doses.

[0207] Compound 29 was supplied as an orange powder by Brightseed Inc. For formulation, a vehicle of 10% dimethyl sulfoxide (DMSO) in 20% hydroxypropyl beta-cyclodextrin (HPBC) was used. For a 30 mg / kg dose concentration, 45 mg of compound 29 was weighed and dissolved in a total volume of 15 mL (1.5 mL DMSO + 13.5 mL 20% HPBC). After weighing, compound 29 was dissolved in the calculated volume of vehicle. To ensure proper mixing and dissolution, the solution was sonicated, 10 μL of NaOH was added in one portion, and then sonicated again until no solids remained, resulting in a viscous, dark red solution. This procedure was repeated for all doses.

[0208] Compound 13 was supplied as a yellow powder by Ambeed, Inc. For formulation, a vehicle of 10% dimethyl sulfoxide (DMSO) in 20% hydroxypropyl beta-cyclodextrin (HPBC) was used. For a 30 mg / kg dose concentration, 45 mg of compound 13 was weighed and dissolved in a total volume of 15 mL (1.5 mL DMSO + 13.5 mL 20% HPBC). After weighing, compound 13 was dissolved in the calculated volume of vehicle. To ensure proper mixing and dissolution, the solution was sonicated, 10 μL of NaOH was added in one portion, and then sonicated again until no solids remained, resulting in a bright yellow solution. This procedure was followed for all doses.

[0209] A compound is considered to be intolerable if three or more adverse effects (or any severe adverse effects) occur at a particular dose during the entire 60-minute period. After compound administration, animals were observed for adverse effects such as significant piloerection, abnormal breathing, hunching, vocalization, and decreased activity. Decreased activity is determined when the animal exhibits decreased activity and stops moving around the cage without sleeping. Mild - slightly decreased activity and responsive when challenged. Moderate - decreased activity and little response when challenged. Pica indicates that the animal was eating non-food items such as bedding. The results of Example 5 are summarized in Table 3 below. [Table 4]

[0210] In summary, all animals receiving all four doses of compounds 26, 21, 29, and 13 (30, 100, 315, and 500 mg / kg) can be considered well tolerated. With respect to the use of virtually any plural and / or singular term herein, one of skill in the art can convert from plural to singular and / or from singular to plural as appropriate to the context and / or application. For clarity, various singular / plural permutations may be explicitly set forth herein.

[0211] In general, those skilled in the art will understand that the terms used in this specification, and particularly in the appended claims (e.g., the body of the appended claims), are generally intended as "open" terms (e.g., the term "comprises" should be interpreted as "including, but not limited to," the term "having" should be interpreted as "having at least," the term "including" should be interpreted as "including, but not limited to," etc.). As those skilled in the art will further understand, if a specific number of introduced claim recitations is intended, such intention will be explicitly stated in the claim; in the absence of such statement, no such intention exists. For example, as an aid to understanding, the following appended claims may include the use of the introductory phrases "at least one" and "one or more" to introduce claim recitations. However, the use of such expressions should not be interpreted as meaning that introducing a claim recitation with the indefinite article "a" or "an" limits a particular claim containing such an introduced claim recitation to embodiments containing only one such recitation, even if the same claim contains the introductory phrases "one or more" or "at least one" and an indefinite article such as "a" or "an" (e.g., "a" and / or "an" should be interpreted to mean "at least one" or "one or more"); the same is true for the use of definite articles used to introduce claim recitations. Moreover, even if a specific number of introduced claim recitations is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number of times (e.g., the bare recitation of "two recitations" without other modifiers means at least two recitations, or more than two recitations). Furthermore, when phrases similar to "at least one of A, B, and C, etc." are used, such configurations are generally intended in the sense that one of ordinary skill in the art would understand the phrase (e.g., "a system having at least one of A, B, and C" includes, but is not limited to, systems of A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, etc.).

[0212] When a convention similar to "at least one of A, B, and C, etc." is used, such configuration is generally intended in the sense that one of ordinary skill in the art would understand the convention (e.g., "a system having at least one of A, B, and C" includes, but is not limited to, systems of A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, etc.). Those of ordinary skill in the art will further understand that whether in this specification, claims, or drawings, virtually any conjunction word and / or phrase presenting two or more alternative terms should be understood to contemplate the possibility of including one of the terms, either of the terms, or both terms. For example, the phrase "A or B" is understood to include the possibilities of "A" or "B" or "A and B."

[0213] Additionally, where features or aspects of the disclosure are described in terms of a Markush group, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0214] As will be understood by those skilled in the art, all ranges disclosed herein encompass any and all possible subranges and combinations thereof for all purposes, such as in terms of providing a written description. Any recited range can be broken down into at least equal halves, thirds, quarters, fifths, tenths, etc., and readily recognized as being fully described. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third, upper third, etc. Also, as will be understood by those skilled in the art, all terms such as "up to," "at least," "greater than," "less than," etc., refer to ranges that are inclusive of the recited numbers and can subsequently be broken down into subranges, as described above. Finally, as will be understood by those skilled in the art, ranges include individual members. Thus, for example, a group having 1 to 3 items refers to a group having 1, 2, or 3 items. Similarly, a group having 1 to 5 items refers to a group having 1, 2, 3, 4, or 5, etc. While various aspects and embodiments have been disclosed herein, other aspects and embodiments will be apparent to those skilled in the art. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope and spirit being indicated by the following claims.

Claims

1. 1. An oral composition for improving, restoring, regulating, or maintaining sleep, said oral composition comprising: a compound of formula (I); 【Chemistry 1】 (In the formula, R １ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; R ２ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; R ３ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; R ４ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; R ５ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; R ６ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; R ７ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; L is -Z １ -Z ２ or Z １ -Z ２ -Z ３ and Z １ is -CH ２ -, -O-, -NH-, optionally substituted C ３ ~C ８ Cycloalkyl, optionally substituted C ６ ~C １０ Aryl, optionally substituted -C ３ ~C ８ heterocyclyl, or optionally substituted C ３ ~C １０ In some embodiments, Z1 is optionally substituted -C ３ ~C ８ is heterocyclyl; Z ２ is hydrogen, deuterium, halo, -CH ２ -, -O-, -CO ２ H, -CO ２ CHCH—, optionally substituted —C ３ ~C ８ Cycloalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted -C ３ ~C ８ heterocyclyl, or optionally substituted -C ３ ~C １０ is heteroaryl; Z ３ is hydrogen, deuterium, halo, -CH ２ -, -O-, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted -C ３ ~C ８ heterocyclyl, or optionally substituted -C ３ ~C １０ Heteroaryl) and one or more carriers or excipients.

2. 2. The oral composition of claim 1, wherein the compound is represented by formula (IA): 【Chemistry 2】

3. 2. The oral composition of claim 1, wherein the compound is represented by formula (IB): 【Transformation 3】

4. The oral composition of any one of claims 1 to 3, wherein the compound is derived from a plant extract.

5. The aforementioned plant extract, Eupatorium perfoliatum, Zingiber officinale, Picea sitchensis, Viburnum davidii, Arnica montana, Helianthus annuus, Lettuce sativa、BASadesia spinosa、Dolomiaea souliei、Saussurea costus、Artemisia annua、Inula helenium、Laurus nobilis、Momodica Cochinchinensis, Pogostemon cablin, Tanacetum parthenium, Cichorium intybus, Solidago canadensis, Horeum vulgare, Tricum aestivum, Silene conica, Alloteropsis semialata, Paris polyphylla, Camellia sinensis, Glebion cornaria, Hordeum vulgare, Setaria italic, Zea mys、Aabidōpsis thaliana、B｡achypodium distachyon、Grindelia integrifolia、Lobelia chinasis、Arachis hypogaea、Nepenthes khasiana、Selaginella mollendorffii、Taxus x media、Acorus gramieus、Andrographis paniculata、Artemisia maritima、Bletilla striata、Fallòopia Multiflora, Gossypium hirsutum, Hordeum spontaneous, Hypericum perforatum, Musa acuminate, Oryza rufipogon, Oryza sativa, Quercus suber, Solanum tuberosum, Valeriana officinalis, Vitis vinifera, Polygonatum odoratum, Glycine max, Panicum virgatum cv. Trailblazer, Clausena5. The oral composition of claim 4, wherein the active ingredient is selected from the group consisting of: Acanthus excavata, Gynura procumbens, Psidium guajava, Eruca vesicaria, Senna alexandrina, or Populus trichorarpa.

6. The plant extract may further comprise: costunolide, 5a,9-dimethyl-3-methylidene-3ah,4h,5h,9bh-naphtho[1,2-b]furan-2,8-dione, bainol A, (3r,3ar,4r,11as)-3,6,10-trimethyl-2-oxo-3h,3ah,4h,7h,8h,11h,11ah-cyclodeca[b]furan-4-yl acetate, (3r,3as,4r,11as)-4-hydroxy-3,6,10-trimethyl-3h,3ah,4h,7h,8h,11h,11ah-cyclodeca[b]furan-4-yl acetate, Furan-2-one, 1R,2S,5S,6S,7S)-5-isopropyl-2,8-dimethyltricyclo[4.4.0.02,7]dec-8-en-4-one, 2-((1R,3S,4R)-4-methyl-3-(prop-1en-2-yl)-4-vinylcyclohexyl)acrylaldehyde, 3,7,11-trimethyldodeca-1,3,5,8,10-pentaene, p-cymene, (1S,2R,4R,7E,11S)-4,8-dimethyl-12-methylidene-3,14-dioxatricyclo[9.3.0.02, 4]tetradec-7-en-13-one, 3-[(3aS,4R,5R,8aR)-4-hydroxy-5,7-dimethyl-3-methylidene-2-oxo-4,5,8,8a-tetrahydro-3aH-cyclohepta[b]furan-6-yl]propyl acetate, 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxychromen-4-one, 5,7-dihydroxy-2-(4-hydroxyphenyl)-3,6-dimethoxychromene -4-one, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxymethyl]oxan-2-yl]oxychromen-4-one, 1-(2-hydroxy-4-methoxyphenyl)-3-(4-hydroxyphenyl)propan-1-one, 3-(4-hydroxyphenyl)-1-[4-hydroxy-2-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]propan-1-one, 3-(4-hydroxyphenyl)-1-[4-methoxy-2-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]propan-1-one, 3-(4-hydroxyphenyl)-1-[2-hydroxy-4-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]propan-1-one, (2S,3S,4S,5R,6S)-6-[5,7-dihydroxy -2-(4-hydroxyphenyl)-4-oxochromen-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid, 7-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, 3-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl) ethyl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, 3-[(2S,5R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2S,3S,5R)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, acetic acid [(2R,3S,4 S,5R,6S)-6-[3,5-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-8-methoxy-4-oxochromen-7-yl]oxy-3,4-dihydroxy-5-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]methyl, 5,7-dihydroxy-2-(4-hydroxyphenyl)-3-[(2S,3R,4S,5S)-3,4,5-trihydroxyoxan-2-yl]oxychromen-4-one, 3-[(2S,3R,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, (2S,3S,4S,5R,6S)-6-[4-(5,7-dihydroxy-3,6-dimethoxy-4-oxochromen-2-yl)-2-hydroxyphenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one, 1,6-dihydroxy-3-methyl-8-[(2S,3R,4 S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyanthracene-9,10-dione, 1,3,8-trihydroxy-6-methylanthracene-9,10-dione, (E)-3-(4-hydroxyphenyl)-N-[4-[[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]-[3-[[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]amino]propyl]amino]butyl]prop-2-enamide, 5,7-dihydroxy-6-methoxy-2-(4-methyl)anthracene-9,10-dione, 1,3,8-trihydroxy-6-methylanthracene-9,10-dione, (E)-3-(4-hydroxyphenyl)-N-[4-[[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]amino]propyl]amino]butyl]prop-2-enamide, (E)-3-(4-hydroxyphenyl)-N-[3-[[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]-[4-[[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]-2-(3,4-di ...

6. The oral composition according to claim 4 or 5, comprising a compound selected from the group consisting of (1S,3R,4R,5R)-3,4-bis[[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]amino]propyl]amino]butyl]amino]propyl]prop-2-enamide, (1S,3R,4R,5R)-3,4-bis[[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy]-1,5-dihydroxycyclohexane-1-carboxylic acid, and 5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one.

7. 7. The oral composition of any one of claims 1 to 6, wherein the oral composition is formulated as a dietary supplement, a food ingredient or additive, a medical food, a nutraceutical composition, or a pharmaceutical composition.

8. The oral composition of any one of claims 1 to 7, wherein the oral composition is in a dosage form configured as one of a soft gel capsule, a hard capsule, a liquid, a powder, and a tablet.

9. The oral composition of any one of claims 1 to 8, wherein the oral composition comprises 0.01% to 99% w / w of the compound of formula (I).

10. The oral composition of any one of claims 4 to 9, wherein the oral composition comprises 0.01% to 99% w / w of the plant extract.

11. The oral composition of any one of claims 1 to 10, wherein the oral composition further comprises a preservative.

12. The oral composition of any one of claims 1 to 11, wherein the oral composition further comprises a sweetener.

13. The oral composition of any one of claims 1 to 12, wherein the oral composition further comprises a colorant.

14. The oral composition according to any one of claims 1 to 13, further comprising an additive.

15. The oral composition of any one of claims 1 to 14, wherein the oral composition further comprises a flavoring agent.

16. 16. The oral composition of any one of claims 1 to 15, wherein the compound of formula (I) consists essentially of compounds 12, 13, 14, 15, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 33, 34, 35, and 38 and is not bound to lignocellulosic material.

17. The oral composition of any one of claims 1 to 16, provided that the oral composition does not contain lignin, cellulose, or pectin.

18. The oral composition of any one of claims 1 to 3, provided that said compound of formula (I) is not an extract from a natural source.

19. 19. The oral composition of any one of claims 1 to 18, wherein the compound of formula (I) is selected from compounds 14, 22, 23, and 26.

20. 20. The oral composition of claim 19, wherein the compound of formula (I) is selected from compounds 22 and 23.

21. The oral composition of any one of claims 1 to 20, wherein the oral composition is formulated as a solid.

22. 22. The oral composition of claim 21, wherein the solid is a food product, a tablet, or a capsule.

23. 12. The oral composition of claim 11, wherein the preservative is from about 0.01% to about 5% by weight of the composition.

24. The oral composition further comprises a compound of formula (II): 【Chemistry 4】 or a salt thereof, wherein R １ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; R ２ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; R ３ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; L is -Z １ -Z ２ or Z １ -Z ２ -Z ３ and Z １ is -CH ２ -, -O-, -NH-, optionally substituted C ３ ~C ８ Cycloalkyl, optionally substituted C ６ ~C １０ Aryl, optionally substituted -C ３ ~C ８ heterocyclyl, or optionally substituted C ３ ~C １０ In some embodiments, Z1 is optionally substituted -C ３ ~C ８ is heterocyclyl; Z ２ is hydrogen, deuterium, halo, -CH ２ -, -O-, -CO ２ H, -CO ２ CHCH—, optionally substituted —C ３ ~C ８ Cycloalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted -C ３ ~C ８ heterocyclyl, or optionally substituted -C ３ ~C １０ is heteroaryl; and Z ３ is hydrogen, deuterium, halo, -CH ２ -, -O-, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted -C ３ ~C ８ heterocyclyl, or optionally substituted -C ３ ~C １０ The oral composition of any one of claims 1 to 23, wherein the compound is heteroaryl.

25. 25. The oral composition of claim 24, wherein the compound of formula (II) is compound 16, 17, 18 or 19.

26. The oral composition further comprises a compound of formula (III), or a salt thereof: 【Transformation 5】 In the formula, R １ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; R ２ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; R ３ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; R ４ is H, deuterium, hydroxyl, halogen, cyano, optionally substituted amino, optionally substituted —C １ ~C ６ Alkyl, optionally substituted —O—C １ ~C ６ Alkyl, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted —O—C ３ ~C ８ Cycloalkyl, optionally substituted -C ３ ~C ８ Heteroalkyl, optionally substituted —O—C ３ ~C ８ Heteroalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted —O—C ６ ~C １０ aryl, or L; L is -Z １ -Z ２ or Z １ -Z ２ -Z ３ and Z １ is -CH ２ -, -O-, -NH-, optionally substituted C ３ ~C ８ Cycloalkyl, optionally substituted C ６ ~C １０ Aryl, optionally substituted -C ３ ~C ８ heterocyclyl, or optionally substituted C ３ ~C １０ In some embodiments, Z1 is optionally substituted -C ３ ~C ８ is heterocyclyl; Z ２ is hydrogen, deuterium, halo, -CH ２ -, -O-, -CO ２ H, -CO ２ CHCH—, optionally substituted —C ３ ~C ８ Cycloalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted -C ３ ~C ８ heterocyclyl, or optionally substituted -C ３ ~C １０ is heteroaryl; and Z ３ is hydrogen, deuterium, halo, -CH ２ -, -O-, optionally substituted -C ３ ~C ８ Cycloalkyl, optionally substituted -C ６ ~C １０ Aryl, optionally substituted -C ３ ~C ８ heterocyclyl, or optionally substituted -C ３ ~C １０ The oral composition of any one of claims 1 to 25, which is heteroaryl.

27. 27. The oral composition of claim 26, wherein the compound of formula (III) is compound 30 or 31.

28. 28. The oral composition of any one of claims 1 to 27, wherein the oral composition comprises an orexin receptor 2 antagonist.

29. 29. The oral composition of any one of claims 1 to 28, wherein the oral composition comprises an orexin receptor 1 antagonist.

30. 1. A method of improving, restoring, regulating, or maintaining sleep in a subject in need thereof, comprising:

30. The method of claim 1, wherein the oral composition is administered wherein the oral composition is administered in an amount sufficient to improve, restore, regulate, or maintain sleep in a subject in need of sleep.

31. 31. The method of claim 30, wherein administration of the oral composition further results in a decrease in pERK1 / 2 phosphorylation.

32. 32. The method of claim 30 or 31, wherein administration of the oral composition further results in a decrease in calcium influx.

33. 33. The method of any one of claims 30 to 32, wherein improving sleep results in the subject sleeping through the night.

34. 34. The method of any one of claims 30 to 33, wherein improving sleep provides the subject with a restful night's sleep.

35. 35. The method of any one of claims 30-34, wherein regulating sleep results in an increase in slow wave sleep 1-4 in the subject.

36. 36. The method of any one of claims 30-35, wherein regulating sleep results in an increase in REM sleep in the subject.

37. 37. The method of any one of claims 30-36, wherein regulating sleep reduces the time it takes to fall asleep in the subject.

38. 38. The method of claim 37, wherein the time to sleep onset is from about 15 minutes to about 180 minutes.

39. 39. The method of any one of claims 30-38, wherein regulating sleep increases average sleep time in the subject.

40. 40. The method of claim 39, wherein the average sleep time is increased by about 15 minutes to about 180 minutes.

41. 41. The method of any one of claims 30 to 40, wherein the oral composition is administered to the subject before sleep.

42. 1. A method of treating a sleep disorder in a subject in need thereof, comprising: administering a therapeutically effective amount of an oral composition according to any one of claims 1 to 29; Thereby treating a sleep disorder in a subject in need of treatment.

43. 43. The method of claim 42, wherein administration of the oral composition further results in a decrease in pERK1 / 2 phosphorylation.

44. 44. The method of claim 42 or 43, wherein administration of the oral composition further results in a decrease in calcium influx.

45. 45. The method of any one of claims 42 to 44, wherein the sleep disorder is selected from the group consisting of insomnia, sleep-related breathing disorders, central hypersomnia disorders, circadian rhythm sleep-wake disorders, parasomnias, and sleep-related movement disorders.

46. 46. ​​The method of any one of claims 42 to 45, wherein the sleep disorder is selected from the group consisting of insomnia, narcolepsy, hypersomnia, sleep apnea, periodic limb movement disorder, restless legs syndrome, nocturnal eating syndrome, jet lag, shift work sleep disorder, irregular sleep-wake patterns, confusional awakenings, sleepwalking, sleep terrors, sleep talking, nightmares, sleep paralysis, REM sleep behavior disorder, snoring, and sleeping sickness.

47. 47. The method of any one of claims 42 to 46, wherein the orexin receptor is activated or restored following administration of the oral composition.

48. 48. The method of any one of claims 42 to 47, wherein the oral composition is administered to the subject before sleep.

49. 49. The method of any one of claims 42-48, further comprising administering an additional compound to treat the sleep disorder.

50. The additional compound for treating the sleep disorder is selected from the group consisting of sedatives, hypnotics, anxiolytics, antipsychotics, anxiolytics, antihistamines, benzodiazepines, barbiturates, cyclopyrrolones, GABA agonists, 5HT-2 antagonists, histamine antagonists, imidazopyridines, secondary sedatives, melatonin agonists and antagonists, melatonergic agents, prokineticin agonists and antagonists, pyrazolopyrimidines, T-type calcium channel antagonists, triazolopyridines, melatonin, mephobarbital, meprobamate, methaqualone, methyprylon, midaneflur, midazolam, modafinil, mefazodone, NGD-2-7 3, nisobamate, nitrazepam, nortriptyline, nortriptyline, oxazepam, paraldehyde, paroxetine, pentobarbital, perlapine, perphenazine, phenelzine, phenobarbital, prazepam, promethazine, propofol, protriptyline, quazepam, ramelteon, reclazepam, loretamide, secobarbital, sertraline, suproclon, TAK-375, temic acid, cyclopyrrolone, GABA agonists, 5HT-2 antagonists, histamine antagonists, imidazopyridines, secondary sedatives, melatonin agonists and antagonists, melatonergic agents, prokineticin agonists andAntagonists, pyrazolopyrimidines, T-type calcium channel antagonists, triazolopyridines, melatonin, mephobarbital, meprobamate, methaqualone, methyprylon, midaneflur, midazolam, modafinil, mefazodone, NGD-2-73, nisobamate, nitrazepam, nortriptyline, nortriptyline, oxazepam, paraldehyde, paroxetine, pentobarbital, perlapine, perphenazine, phenelzine, phenobarbital, prazepam, promethazine, propofol, pro 50. The method of claim 49, wherein the agonist is selected from the group consisting of: tryptyline, quazepam, ramelteon, levazepam, loretamide, secobarbital, sertraline, suproclon, TAK-375, temazepam, thioridazine, tiagabine, tracazolate, tranylcypromaine, trazodone, triazolam, trepipam, tricetamide, triclofos, trifluperazine, trimetozine, trimipramine, aldazepam, venlafaxine, zaleplon, zolazepam, zopiclone, zolpidem, and combinations thereof.

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