Compositions and methods for modulating sleep and uses thereof

Abstract

Disclosed herein are compositions and methods for improving sleep health benefits by providing compositions and carriers. Some embodiments provided include compounds that, for example, administrate therapeutically effective plant extracts. In some embodiments, the plant extract is herba lycopi perforati. In some embodiments, the plant extract comprises a costunolide.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 508,807, filed June 16, 2023, U.S. Provisional Application No. 63 / 494,995, filed April 7, 2023, and U.S. Provisional Application No. 63 / 384,854, filed November 23, 2022, all of which are incorporated by reference in their entirety.

[0003] Field of the Invention

[0004] The present disclosure relates to compositions and methods for their preparation. In particular, 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 Art

[0005] Good sleep is essential for good physical and mental health and quality of life. Insufficient sleep is associated with a range of adverse health and social outcomes, including poor performance in school and the workplace. Reduced sleep duration is associated with seven of the 15 leading causes of death in the United States, including cardiovascular disease, malignant neoplasms, cerebrovascular disease, accidents, diabetes, sepsis, and hypertension.

[0006] Given the prevalence of chronic diseases related to sleep loss in the current global population, inventions that improve or reduce the adverse effects of sleep loss will have a direct and significant beneficial effect on global human health. Good sleep hygiene can promote optimal sleep duration and quality, such as consistent bedtime and wake-up times, reduced caffeine intake, and managed screen time before bed.

[0007] Therapeutic intervention is the most common treatment for sleep disorders. Currently, there are three FDA-approved molecules for the treatment of insomnia through orexin receptor antagonism: suvorexant, lemborexant, and daridorexant. Several other molecules are under investigation for the treatment of insomnia. However, most treatment options are not suitable for daily use as nutritional interventions.

[0008] Various herbal remedies and dietary supplements are claimed to aid sleep. These include melatonin, valerian root, German chamomile, kava, L-tryptophan, Tilia, verbena, melissa, and Scutellaria. However, these products are not consistently regulated, resulting in variations in ingredient purity and effectiveness. Scientific evidence supporting the effectiveness of these herbal regimens is limited. Most herbal regimens are generally considered safe, but information is lacking regarding how they interact with prescription medications. Melatonin is the most popular regimen for treating insomnia. For optimal effectiveness, 3 mg to 5 mg is typically given several hours before bedtime, especially for occasional use. However, melatonin is not recommended for the long-term management of chronic insomnia. The long-term safety of melatonin is unknown.

[0009] Clearly, there is an unmet need to develop nutritional interventions to improve sleep quality and duration. Summary of the Invention

[0010] Aspects of the present disclosure relate to oral compositions for improving, restoring, regulating, or maintaining sleep. In some embodiments, the oral composition comprises a therapeutically effective amount of a plant extract, and one or more carriers or excipients, wherein the plant extract is capable of improving, restoring, regulating, or maintaining sleep. In some embodiments, the plant extract is selected from the group consisting of: (Eupatorium perfoliatum), ginger (Zingiber officinale) Sitka spruce (Picea sitchensis), Viburnum zedoaria (Viburnum davidii), Arnica (Arnica montana), sunflower (Helianthus annuus), lettuce (Lettuce sativa), Erythrorhizome (Barnadesia spinosa) Chuan Muxiang (Dolomiaea souliei), Cloudwood (Saussurea costus) Artemisia annua (Artemisia annua) Elecampane (Inula helenium) Laurel (Laurus nobilis), Wood turtle fruit (Momodica cochinchinensis) Patchouli (Pogostemon cablin), Brachytongue (Tanacetum parthenium) endive (Chicory intybus) Canada goldenrod (Solidago canadensis), barley (Horeum vulgare) Common wheat (Trick summer)、 Pyrola paniculata (Silene conica) Hairy grass (Alloteropsis semialata) Paris polyphylla (Paris polyphylla)、 Tea (Camella sinensis), Garland chrysanthemum (Glebionis hornaria), barley (Barley common)、 millet (Setaria italic) corn (Zea mays) Arabidopsis thaliana (Arabidopsis thaliana), Brachypodium distachyon (Brachypodium distachyon) Puget Sound Gumweed (Grindelia integrifolia), Lobelia (Lobelia chinensis) peanut (Arachis hypogaea), Nepenthes indicus (Nepenthes khasiana)、 Selaginella chinensis (Selaginella mollendorffii) Mentia yew (Yaxus x media) Acorus (Acorus (gramius)、 Andrographis paniculata (Andrographis paniculata) Artemisia seaweed (Artemisia maritima) Bletilla striata (Bletilla striata) Polygonum multiflorum (Fallopia multiflora) Upland cotton (Gossypium hirsutum) Hordeum vulgare (Spontaneous barley) Hypericum perforatum (Hypericum perforatum), Banana (Muse sharp)、 wild rice (Oryza rufipogon) rice (Rice) Spanish cork oak (Oak (sub)、 potato (Solanum tuberosum), valerian (Valeriana officinalis), Grape (Vitis vinifera), Polygonatum odoratum (Polygonatum odoratum), soybeans (Glycine max), Switchgrass Pioneer cultivar (Panicum virgatum cv. Trailblazer) or Populus trichocarpa ( Populus trichorarpa). In some embodiments, the plant extract comprises a compound selected from the group consisting of: costunolide, 5a,9-dimethyl-3-methylene-3ah,4h,5h,9bh-naphtho[1,2-b]furan-2,8-dione, Baynol A, (3r,3ar,4r,11as)-3,6,10-trimethyl-2-oxo-3h,3ah,4h,7h,8h,11h,11ah-cyclodecano[b]furan-4-yl acetate, (3r,3as,4r,11as)-4-hydroxy-3,6,10-trimethyl-3h,3ah,4h,7h,8h,11h,11ah-cyclodecano[b]furan-2-one, (1 R ,2 S ,5 S ,6 S ,7 S)-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)propenal, 3,7,11-trimethyldodeca-1,3,5,8,10-pentaene, p-isopropyltoluene, (1S,2R,4R,7E,11S)-4,8-dimethyl-12-methylene-3,14-dioxatricyclo[9.3.0.02, 4]tetradec-7-en-13-one, 3-[(3aS,4R,5R,8aR)-4-hydroxy-5,7-dimethyl-3-methylene-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-dimethoxy chromen-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, (2 S ,3 S ,4 S ,5 R ,6 S )-6-[5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxochromen-3-yl]oxy-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid, 7-[(2 S ,3 R ,4 S ,5 S ,6 R )-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2 S ,3 R ,4 R ,5 R ,6 S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, 3-[(2 S ,3 R ,4 S ,5 S ,6 R )-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2 S ,3 R ,4 R ,5 R ,6 S )-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, 3-[(2 S ,5 R )-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2 S ,3 S ,5 R )-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, acetic acid [(2 R ,3 S ,4 S ,5 R ,6 S )-6-[3,5-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-8-methoxy-4-oxochromen-7-yl]oxy-3,4-dihydroxy-5-[(2 S ,3 R ,4 R ,5 R ,6 S )-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]methyl ester, 5,7-dihydroxy-2-(4-hydroxyphenyl)-3-[(2 S ,3 R ,4 S ,5 S )-3,4,5-trihydroxyoxacyclohexane-2-yl]oxychromen-4-one, 3-[(2 S ,3 R ,4 R ,5 S )-3,4-dihydroxy-5-(hydroxymethyl)oxan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, (2 S ,3 S ,4 S,5 R ,6 S )-6-[4-(5,7-dihydroxy-3,6-dimethoxy-4-oxochromen-2-yl)-2-hydroxyphenoxy]-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one, 1,6-dihydroxy-3-methyl-8-[(2 S ,3 R ,4 S ,5 S ,6 R )-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-methoxyphenyl)chromen-4-one, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[(2 S ,3 R ,4 S ,5 S ,6 R )-3,4,5-trihydroxy-6-(hydroxymethyl)oxacyclohexane-2-yl]oxychromen-4-one, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-6-methoxychromen-4-one, ( 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-enoamide, (1 S ,3 R ,4 R ,5 R )-3,4-double[[( 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 dosage form of the oral composition is configured as one of a soft capsule, a hard capsule, a liquid, a powder, and a tablet. In some embodiments, the oral composition comprises 10% to 99% w / w of a plant extract. In some embodiments, the plant extract 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.

[0011] Some aspects of the present disclosure relate to a method for 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 a method for 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 also provides a reduction in calcium influx. In some embodiments, the plant extract also provides a reduction in pERK1 / 2 phosphorylation. In some embodiments, improving sleep provides a complete night's sleep for the subject. In some embodiments, improving sleep provides a restful night's sleep for the subject. In some embodiments, regulating sleep provides an increase in slow-wave sleep stages 1 to 4 for the subject. In some embodiments, regulating sleep provides an increase in REM sleep for 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 disorder, parasomnia, and sleep-related movement disorder. 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, night eating (drinking) syndrome, jet lag, shift work sleep disorder, irregular sleep-wake patterns, confusional arousals, sleepwalking, sleep terrors, sleep talking, nightmares, sleep paralysis, REM sleep behavior disorder, snoring, and sleeping sickness. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The features and advantages of the compositions and methods described herein will become apparent from the following detailed description, which is described 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, similar reference numerals or symbols generally identify similar components unless the context dictates otherwise. The drawings are not drawn to scale.

[0013] Figure 1 Shown are graphs depicting the in vitro biological activity of Compound 20 against orexin receptor 2.

[0014] Figure 2 Shown are graphs depicting the in vitro biological activity of Compound 21 against orexin receptor 2.

[0015] Figure 3 Shown are graphs depicting the in vitro biological activity of Compound 22 against orexin receptor 2.

[0016] Figure 4 Shown are graphs depicting the in vitro biological activity of Compound 23 against orexin receptor 2.

[0017] Figure 5 Shown are graphs depicting the in vitro biological activity of Compound 24 against orexin receptor 2.

[0018] Figure 6 Shown are graphs depicting the in vitro biological activity of Compound 25 against orexin receptor 2.

[0019] Figure 7 Shown are graphs depicting the in vitro biological activity of Compound 26 against orexin receptor 2.

[0020] Figure 8 Shown are graphs depicting the in vitro biological activity of compound 27 against orexin receptor 2.

[0021] Figure 9 Shown are graphs depicting the in vitro biological activity of Compound 28 against orexin receptor 2.

[0022] Figure 10 Shown are graphs depicting the in vitro biological activity of compound 29 against orexin receptor 2.

[0023] Figure 11 Shown are graphs depicting the in vitro biological activity of Compound 30 against orexin receptor 2.

[0024] Figure 12 The results show that compounds 31 to 38 target the orexin receptor (Orx 1 and Orx2) in vitro biological activities. DETAILED DESCRIPTION

[0025] The present disclosure particularly provides the discovery of compounds, compositions and methods for improving, restoring, regulating or maintaining sleep in a subject. In aspects, the composition comprises one or more compounds described herein and a carrier. In some aspects, the method comprises orally administering one or more compounds described herein or compositions described herein to improve, restore, regulate or maintain sleep in a subject. In some embodiments, the oral composition can, for example, promote the maintenance of sleep, thereby achieving a restful night's sleep, further improving a person's sleep quality. The oral compositions described herein, employed in various embodiments of the present disclosure, have been shown to be antagonists of certain receptors that may be associated with the induction and regulation of sleep.

[0026] Additionally, the oral compositions disclosed herein can also be used to regulate satiety or conditions associated with satiety.

[0027] definition

[0028] Unless otherwise expressly defined, the technical and / or scientific terms used herein have the same meaning as those generally understood by those of ordinary skill in the art. If a term in this document has multiple definitions, the definition in this section shall prevail unless otherwise indicated. Unless the context clearly dictates otherwise, the singular forms "a," "an," and "the" as used in this specification and the appended claims include plural referents. Unless otherwise indicated, the conjunctions "or" and "and" are used to mean "and / or." In addition, the use of the terms "including" and other forms, such as "includes" and "included," is not limited. As used in this specification, in transitional phrases or in the body of the claims, the terms "comprise(s) and comprising" should be interpreted as having an open-ended meaning. That is, these terms should be interpreted synonymously with the phrases "having at least" or "comprising at least." When used in the context of a method, the term "comprising" means that the method includes at least the steps listed, 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.

[0029] When a range of values ​​is provided, it is understood that the upper and lower limits of the range and every intervening value between the upper and lower limits of that range are encompassed within the embodiments.

[0030] Although the present disclosure has been illustrated and described in detail in the foregoing description, such description should be considered illustrative or exemplary rather than restrictive. The present disclosure is not limited to the disclosed embodiments. Variations of the disclosed embodiments can be understood and implemented by those skilled in the art in practicing the claimed disclosure, based on a study of the present disclosure and the appended claims.

[0031] All references cited herein are incorporated by reference in their entirety. To the extent that publications and patents or patent applications incorporated by reference contradict the disclosure contained in this specification, this specification is intended to supersede and / or take precedence over any such contradictory material.

[0032] The compounds disclosed herein with at least one chiral center can exist as racemates or in the form of respective enantiomers, and can exist in the form of enantiomer-enriched mixtures of enantiomers. It should be noted that all of these isomers and mixtures thereof are included within the scope of the present invention. In addition, the crystalline forms of the compounds disclosed herein can exist in the form of alternative polymorphs. Such polymorphs are included in one embodiment of the present invention. In addition, some compounds in the compounds of the present invention can form solvates with water (i.e., hydrates) or common organic solvents. Such solvates are included in one embodiment of the present invention.

[0033] As used herein, the term "pharmaceutically acceptable salt" refers to a salt of a compound that does not produce significant stimulation to the organism being administered, nor does it eliminate the biological activity and properties of the compound. In some embodiments, the salt is an acid addition salt of the compound. Pharmaceutically acceptable salts can be obtained by reacting the compound with an inorganic acid (such as a hydrohalic acid (e.g., hydrochloric acid or hydrobromic acid), sulfuric acid, nitric acid, phosphoric acid, etc.). Pharmaceutically acceptable salts can also be obtained by reacting the compound with an organic acid (such as an aliphatic or aromatic carboxylic acid 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). Pharmaceutically acceptable salts can also be obtained by reacting a compound with a base to form salts such as ammonium salts, alkali metal salts such as sodium salts or potassium salts, alkaline earth metal salts such as calcium salts or magnesium salts, salts of organic bases such as dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, C1-C7 alkylamine, cyclohexylamine, triethanolamine, ethylenediamine, and salts with amino acids such as arginine salts, lysine salts, and the like.

[0034] 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. Unless any conventional media or agents are incompatible with the active ingredient, it is contemplated that they will be used in therapeutic compositions. In addition, various adjuvants such as those commonly used in the art may also be included. Considerations for including various components 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, which are incorporated herein by reference in their entirety.

[0035] As used herein, the term "halogen" means any of the radiostable atoms of column 7 of the periodic table, for example, fluorine, chlorine, bromine, or iodine.

[0036] Any amine, hydroxyl, or carboxyl side chain on the compounds disclosed herein may be esterified or amidated. The procedures and specific groups used to achieve this are known to those skilled in the art and can be found in, for example, Greene and Wuts, Protective Groups in Organic Synthesis, 3rd ed. These are readily available from the references at John Wiley & Sons, New York, NY, 1999, which is incorporated herein in its entirety.

[0037] As used herein, “C a to C b ” or “C a -C b” (where “a” and “b” are integers) refers to the number of carbon atoms in an alkyl group, alkenyl group, or alkynyl group, or the number of carbon atoms in the ring of a cycloalkyl group, aryl group, heteroaryl group, or heterocyclyl group. That is, the ring of an alkyl, alkenyl, alkynyl, cycloalkyl group, aryl group, heteroaryl group, or heterocyclyl group can contain from “a” to “b” (inclusive) carbon atoms. Thus, for example, a “C1 to C4 alkyl” group or a “C1-C4 alkyl” group refers to all groups having 1 to 4 carbon atoms. Alkyl groups, i.e., CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)-, and (CH3)3C-. Similarly, for example, a cycloalkyl group can contain a total of "a" to "b" (inclusive) atoms, such as a C3-C8 cycloalkyl group, which has 3 to 8 carbon atoms in the ring. If "a" and "b" are not specified with respect to an alkyl, cycloalkyl, or cycloalkenyl group, it is assumed that the atoms in these definitions are "a" to "b" (inclusive). The broadest range described. Similarly, a "4- to 7-membered heterocyclyl" group refers to all heterocyclyl groups having a total of 4 to 7 ring atoms, for example, 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 C-C alkyl, C-C alkyl, etc. Similarly, C-C carbocyclyl or cycloalkyl each include hydrocarbon rings containing 3, 4, 5, 6, 7 and 8 carbon atoms, or a range defined by either of the two numbers, such as C-C cycloalkyl or C-C cycloalkyl. For example, 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 two aforementioned numbers, such as 4 to 6 membered heterocyclyl or 5 to 7 membered heterocyclyl.

[0038] As used herein, "alkyl" refers to a straight or branched hydrocarbon chain comprising a fully saturated (no double or triple bond) hydrocarbon group. An alkyl group may have 1 to 20 carbon atoms (whenever it appears in this article, a numerical range such as "1 to 20" refers to each integer within a given range; for example, "1 to 20 carbon atoms" means that the alkyl group may be composed of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc. up to 20 carbon atoms (including 20 carbon atoms), but this definition also encompasses the case of the term "alkyl" without a specified numerical range). An alkyl group may also be a medium-sized alkyl group having 1 to 10 carbon atoms. An alkyl group may also be a low-carbon number alkyl group having 1 to 5 carbon atoms. The alkyl group of a compound may be designated as "C1-C4 alkyl" or similar designations. For example, "C1-C4 alkyl" indicates that the alkyl chain has one to four carbon atoms, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl. Typical alkyl groups include, but are in no way limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, ethenyl, propenyl, butenyl, and the like.

[0039] The alkyl group may also be substituted or unsubstituted. When substituted, the substituent groups are individually and independently selected from one or more of the following groups: alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclic, aralkyl, heteroaralkyl, (heteroalicyclic)alkyl, hydroxy, protected hydroxy, alkoxy, aryloxy, acyl, ester, sulfhydryl, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl Optionally substituted amino groups include C-amino, N-amino, S-sulfonamido, N-sulfonamido, C-carboxyl, protected C-carboxyl, O-carboxyl, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino (including monosubstituted and disubstituted amino groups), and protected derivatives thereof. Regardless of whether a substituent is described as "optionally substituted," the substituent may be substituted with one of the substituents listed above.

[0040] As used herein, "cycloalkyl" refers to a fully saturated (no double bonds) monocyclic or polycyclic hydrocarbon ring system. When the ring consists of two or more rings, these rings can be connected together in a fused, bridged or spiro manner. The range of cycloalkyl groups can be C3 to C 10In some embodiments, the cycloalkyl group may be unsubstituted or substituted. Typical cycloalkyl groups include, but are by no means limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. Unless otherwise indicated, if substituted, the substituents may be alkyl or selected from those indicated above for substitution of alkyl groups. When substituted, the substituents on the cycloalkyl group may form an aromatic ring fused to the cycloalkyl group, including aryl and heteroaryl groups.

[0041] 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. A heteroalkyl group can have from 1 to 20 carbon atoms, but this definition also encompasses the case where the term "heteroalkyl" is not specified in a numerical range. A heteroalkyl group can also be a medium-sized heteroalkyl group having from 1 to 9 carbon atoms. A heteroalkyl group can also be a low-sized heteroalkyl group having from 1 to 4 carbon atoms. The heteroalkyl group of a compound can be designated as "C 1-4 Heteroalkyl" or similar designations. A heteroalkyl group may contain one or more heteroatoms. By way of example only, "C 1-4 "Heteroalkyl" means a heteroalkyl group having from one to four carbon atoms in the chain and one or more heteroatoms in the backbone of the chain.

[0042] As used herein, the term "amino" refers to "-NR A R B " group, wherein R A and R B are each independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl are as defined herein.

[0043] As used herein, "aryl" refers to a carbocyclic ring (full carbon) or two or more fused rings (rings having two adjacent carbon atoms) with a completely delocalized π electron system. Examples of aryl groups include, but are not limited to, benzene, naphthalene, and azulene. Aryl groups may be substituted or unsubstituted. When substituted, the hydrogen atoms are replaced by substituent groups independently selected from one or more of the following groups: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclic, aralkyl, heteroaralkyl, (heteroalicyclic) alkyl, hydroxyl, protected hydroxyl, alkoxy, aryloxy, acyl, ester, sulfhydryl, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N- In some embodiments, the aryl group may be a thiocarbamoyl group, a C-amino group, an N-amino group, an S-sulfonamido group, an N-sulfonamido group, a C-carboxyl group, a protected C-carboxyl group, an O-carboxyl group, an isocyanato group, a thiocyanato group, an isothiocyanato group, a nitro group, a silyl group, a sulfenyl group, a sulfinyl group, a sulfonyl group, a haloalkyl group, a haloalkoxy group, a trihalomethanesulfonyl group, a trihalomethanesulfonamido group, and an amino group (including monosubstituted amino groups and disubstituted 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 groups, cycloalkenyl groups, cycloalkynyl groups, and heterocyclyl groups.

[0044] As used herein, "heteroaryl" refers to a monocyclic or polycyclic aromatic ring system (a ring system with a completely delocalized π electron system), one or two 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, the hydrogen atom is replaced by a substituent group independently selected from one or more of the following groups: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclic, aralkyl, heteroaralkyl, (heteroalicyclic)alkyl, hydroxy, protected hydroxy, alkoxy, aryloxy, acyl, ester, sulfhydryl, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N- In some embodiments, the present invention includes but is not limited to alkyl, alkyl, alkyl, alkylene ...

[0045] As used herein, "heterocyclyl" refers to a non-aromatic ring or ring system containing at least one heteroatom in the ring backbone. The heterocyclyl group can be connected together in a fused, bridged or spiro manner. The heterocyclyl group can have any degree of saturation, as long as at least one ring in the ring system is not an aromatic ring. The heteroatom can be present in a non-aromatic ring or an aromatic ring in the ring system. The heterocyclyl group can have 3 to 20 ring members (i.e., the number of atoms (including carbon atoms and heteroatoms) that constitute the ring backbone), but this definition also covers the case of the term "heterocyclyl" without specifying a numerical range. The heterocyclyl group can also be a medium-sized heterocyclyl with 3 to 10 ring members. The heterocyclyl group can also be a heterocyclyl with 3 to 6 ring members. The heterocyclyl group can be designated as "3 to 6-membered heterocyclyl" or similar names. In preferred six-membered monocyclic heterocyclyls, the heteroatoms are selected from one to a maximum of three of O, N, or S, and in preferred five-membered monocyclic heterocyclyls, the heteroatoms are selected from one heteroatom or two heteroatoms of O, N, or S. Examples of heterocyclyl rings include, but are not limited to, azaquinyl, acridinyl, carbazolyl, cinnolinyl, dioxolanyl, imidazolinyl, imidazolidinyl, morpholinyl, oxiranyl, oxepanyl, thiepanyl, piperidinyl, piperazinyl, dioxopiperazinyl, pyrrolidinyl, pyrrolidonyl, pyrrolidinedionyl, 4-piperidonyl, pyrazolinyl, pyrazolidinyl, 1,3-dioxinyl, 1,3-dioxinyl, 1,4-dioxinyl, 1,4-dioxinyl, 1,3-oxathianyl, 1,4-oxathianyl, 1,4-oxathianyl, 2-oxathianyl, 1,2-oxathianyl, 1,3-oxathianyl, 1,4-oxathianyl, 2 ... H -1,2-oxazinyl, trioxanyl, hexahydro-1,3,5-triazinyl, 1,3-dioxolyl, 1,3-dioxolanyl, 1,3-dithiolanyl, 1,3-dithiolanyl, isoxazolinyl, isoxazolidinyl, oxazolinyl, oxazolidinyl, oxazolidinone, thiazolinyl, thiazolidinyl, 1,3-oxathiolanyl, indolinyl, isoindolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, tetrahydro-1,4-thiazinyl, thiamorpholinyl, dihydrobenzofuranyl, benzimidazolidinyl and tetrahydroquinoline.

[0046] As used herein, the terms "purified," "substantially purified," and "isolated" mean that the compounds disclosed herein are free from other, different compounds with which the compounds of the invention are normally associated in their native state, 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 a given sample.

[0047] Substituted groups are based on or derived from unsubstituted parent groups in which one or more hydrogen atoms are replaced by another atom or group. Unless otherwise indicated, when a group is considered to be "substituted" or "optionally substituted", the group is substituted by one or more substituents independently selected from the group consisting of: C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C3-C7 carbocyclyl (optionally substituted by halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C3-C7 carbocyclyl-C1-C6 alkyl (optionally substituted by halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C3-C7 carbocyclyl-C1-C6 alkyl (optionally substituted by halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C3-C7 carbocyclyl-C1-C6 alkyl (optionally substituted by halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C3-C7 carbocyclyl-C1-C6 alkyl (optionally substituted by halo, C1-C6 C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 5-10 membered heterocyclyl (optionally substituted by halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 5-10 membered heterocyclyl-C1-C6 alkyl (optionally substituted by halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), aryl (optionally substituted by halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), aryl (optionally substituted by halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), aryl(C1-C6)alkyl (optionally substituted by halo, C1-C6 C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy optionally substituted), 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 (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy optionally substituted), halo, cyano, hydroxy, C1-C6 alkoxy, C1-C6 alkoxy(C1-C6)alkyl (i.e., ether ), aryloxy, mercapto (sulfhydryl), 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-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-amine, N-amine, S-sulfonamido, N-sulfonamido, C-carboxyl, O-carboxyl, acyl, cyanato, isocyanato, thiocyanato, isothiocyanato, sulfinyl, sulfonyl, and oxo (=O). Regardless of whether a group is described as "optionally substituted," the group may be substituted with the substituents described above.

[0048] As used herein, the term "subject" refers to a human or non-human mammal (e.g., dog, cat, mouse, rat, cow, sheep, pig, goat), non-human primate, or bird (e.g., chicken), as well as any other vertebrate or invertebrate.

[0049] It is understood that where compounds disclosed herein have unfilled valences, such valences should be filled with hydrogen and / or deuterium.

[0050] As used herein, the term "about" refers to an amount, level, value, number, frequency, percentage, dimension, size, amount, weight, or length that differs from a reference amount, level, value, number, frequency, percentage, dimension, size, amount, weight, or length by 30%, 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1%. When a value is preceded by the term about, the component is not intended to be strictly limited to that value, but is intended to include amounts that vary from that value.

[0051] Compound

[0052] In some aspects, the present disclosure provides compounds of Formula (I).

[0053]

[0054] (I).

[0055] In some embodiments, Formula (I) is a salt described herein. In some embodiments, the salt is suitable for oral intake. In some embodiments, the salt is a pharmaceutically acceptable salt.

[0056] In some embodiments, Formula (I) is represented by Formula (IA)

[0057] (IA).

[0058] In some embodiments, Formula (I) is represented by Formula (IB)

[0059] (IB).

[0060] In some aspects, the present disclosure provides compounds of Formula (II).

[0061]

[0062] (II).

[0063] In some embodiments, Formula (II) is a salt described herein. In some embodiments, the salt is suitable for oral intake. In some embodiments, the salt is a pharmaceutically acceptable salt.

[0064] In some aspects, the present disclosure provides compounds of formula (III).

[0065]

[0066] (III).

[0067] In some embodiments, Formula (III) is a salt described herein. In some embodiments, the salt is suitable for oral intake. In some embodiments, the salt is a pharmaceutically acceptable salt.

[0068] In some embodiments of the compound of Formula (I), the compound of Formula (IA), the compound of Formula (IB), the compound of Formula (II), or the compound of Formula (III), R 1 It can be selected from 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.

[0069] In some embodiments of the compound of Formula (I), the compound of Formula (IA), the compound of Formula (II), or the compound of Formula (III), R 2 It can be selected from 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.

[0070] In some embodiments of the compound of Formula (I), the compound of Formula (IB), the compound of Formula (II), or the compound of Formula (III), R 3 It can be selected from 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.

[0071] In some embodiments of the compound of Formula (I) or the compound of Formula (IA), R 4 It can be selected from 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.

[0072] In some embodiments of the compound of Formula (I) or the compound of Formula (IB), R 5 It can be selected from 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.

[0073] In some embodiments of the compound of Formula (I) or the compound of Formula (IB), R 6 It can be selected from 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.

[0074] In some embodiments of the compound of Formula (I), R 7 It can be selected from 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.

[0075] In some embodiments of a compound of Formula (I), a compound of Formula (IA), a compound of Formula (IB), a compound of Formula (II), or a compound of Formula (III), L is —Z 1 -Z 2 In some embodiments of the compound of Formula (I), the compound of Formula (IA), the compound of Formula (IB), the compound of Formula (II), or the compound of Formula (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 the compound of formula (I), the compound of formula (IA), the compound of formula (IB), the compound of formula (II), or the compound of formula (III), R 1 -R 7 is L. In some embodiments of the compound of (I), the compound of (IA), the compound of (IB), the compound of (II), or the compound of (III), R 1 -R 7 At least one of is L and L is -Z 1 -Z 2 In some embodiments of the compound of formula (I), the compound of formula (IA), the compound of formula (IB), the compound of formula (II), or the compound of formula (III), R 1 -R 7 Only one of them is L and L is –Z 1 -Z 2 In some embodiments of the compound of formula (I), the compound of formula (IA), the compound of formula (IB), the compound of formula (II), or the compound of formula (III), R 1 -R 7 Only one of the is optionally substituted C3-C8 heterocyclyl.

[0076] In some embodiments of the compound of formula (I), the compound of formula (IA), or the compound of formula (II), Z1 is -CH2-, -O-, -NH-, optionally substituted C3-C8 cycloalkyl, optionally substituted C6 to C8 cycloalkyl, 10 aryl, optionally substituted -C3-C8 heterocyclic group or optionally substituted C3 to C 10 In some embodiments, Z1 is optionally substituted -C3-C8 heterocyclyl.

[0077] In some embodiments of the compound of Formula (I), the compound of Formula (IA), the compound of Formula (IB), the compound of Formula (II), or the compound of Formula (III), Z 2is hydrogen, deuterium, halo, –CH2–, –O–, –CO2H, –CO2CHCH–, optionally substituted –C3-C8 cycloalkyl, optionally substituted –C6-C 10 aryl, optionally substituted -C3-C8 heterocyclic group or optionally substituted -C3-C 10 In some embodiments, Z 2 is an optionally substituted -C3-C8 heterocyclic group.

[0078] In some embodiments of the compound of Formula (I), the compound of Formula (IA), the compound of Formula (IB), the compound of Formula (II), or the compound of Formula (III), Z 3 is hydrogen, deuterium, halo, –CH2–, –O–, optionally substituted –C3-C8 cycloalkyl, optionally substituted –C6-C 10 aryl, optionally substituted -C3-C8 heterocyclic group or optionally substituted -C3-C 10 In some embodiments, Z 2 is an optionally substituted -C3-C8 heterocyclic group.

[0079] In some embodiments, the optionally substituted C3-C8 heterocyclyl is 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 In some embodiments, the optionally substituted C3-C8 heterocyclyl is In some embodiments, the optionally substituted C3-C8 heterocyclyl is 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, for example, not 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 hydrogen, and the compound itself is not a naturally occurring compound.

[0080] In some embodiments, the compound of formula (I), the compound of formula (IA), the compound of formula (IB), the compound of formula (II), or the compound of formula (III) is selected from the compounds of Table A, their salts, or their pharmaceutically acceptable salts. Table A describes compounds according to the present disclosure and may include isomers and stereoisomers of the described compounds. For example, the compounds of Table A can be described as cis-isomers and trans-isomers by drawing the following crossed double bonds: .

[0081] Table A

[0082] In some embodiments, the compound of formula (I) does not include compound 12, compound 13, compound 14, compound 15, compound 20, compound 21, compound 22, compound 23, compound 24, compound 25, compound 26, compound 27, compound 28, compound 29, compound 33, compound 34, compound 35, compound 38, or a combination thereof. In some embodiments, the compound of formula (II) does not include compound 16, compound 17, compound 18, compound 19, or a combination thereof. In some embodiments, the compound of formula (III) does not include compound 30, compound 31, or a combination thereof.

[0083] In some embodiments, the disclosed chemical structure can contain glucosides, or other structures, wherein the sugar moiety is selected from the non-limiting examples of glucose, fructose, galactose, mannose, xylose, rhamnose, sialic acid and sugar derivatives. The metabolites of such structures can vary depending on the specific sugar / glucoside; however, the main metabolic reaction of glucosides is hydrolysis. This process involves the cleavage of the glycosidic bond between the glucose unit and the aglycone (the non-sugar portion of the molecule). An enzyme called glucosidase present in various organisms can promote this reaction. Hydrolysis produces a sugar component (glucose) and aglycone. Therefore, the present disclosure provides aglycone of any one 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 can be produced by isomerizing chalcone with chalcone isomerase (CHI) to generate a flavanone group.

[0084] Salts of the disclosed compounds refer to compounds having the desired pharmacological activity of the parent compound and include: (1) salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; or salts formed with inorganic acids such as 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-ethanediol, 1,3-diol, 1,4-diol, 1,6-diol, 2,7-diol, 3,7 ... (1) acid addition salts formed with organic acids such as alkylenedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, camphorsulfonic acid, 4-toluenesulfonic acid, 4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, and hexanedioic acid; or (2) salts formed when an acidic proton present in the parent compound is replaced.

[0085] It should be understood that in any compound described herein having one or more chiral centers, if absolute stereochemistry is not explicitly stated, each center can independently be in the R configuration or the S configuration, or a mixture thereof. Thus, the compounds provided herein can be enantiomerically pure, enantiomerically enriched, or can be a mixture of stereoisomers, and include all diastereoisomers and enantiomeric forms. In addition, it should also be understood that in any compound described herein having one or more double bonds that produce geometric isomers that can be defined as E or Z, each double bond can independently be E or Z, or a mixture thereof. If necessary, stereoisomers can be obtained by stereoselective synthesis and / or separation of stereoisomers using chiral chromatographic columns. Similarly, it should be understood that in any compound described, all tautomeric forms are also intended to be included.

[0086] It should be understood that the compounds described herein may be isotopically labeled or otherwise labeled, including but not limited to labeling with a chromophore or fluorescent moiety, a bioluminescent marker, or a chemiluminescent marker. Substitution with isotopes such as deuterium can provide certain therapeutic advantages resulting from higher metabolic stability, such as an increased half-life in vivo or a reduced dosage requirement. Each chemical element represented in the compound structure may include any isotope of the element. For example, in a compound structure, a hydrogen atom may be explicitly disclosed, or it may be understood that a hydrogen atom is present in the compound. At any position in the 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, the compounds mentioned herein encompass all potential isotopic forms unless the context clearly dictates otherwise.

[0087] It should be understood that the compounds described herein may be isotopically labeled or otherwise labeled, including but not limited to labeling with a chromophore or fluorescent moiety, a bioluminescent marker, or a chemiluminescent marker. Substitution with isotopes such as deuterium can provide certain therapeutic advantages resulting from higher metabolic stability, such as an increased half-life in vivo or a reduced dosage requirement. Each chemical element represented in the compound structure may include any isotope of the element. For example, in a compound structure, a hydrogen atom may be explicitly disclosed, or it may be understood that a hydrogen atom is present in the compound. At any position in the 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, the compounds mentioned herein encompass all potential isotopic forms unless the context clearly dictates otherwise.

[0088] It should be 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 having the same active type. A conformer is a structure that is an isomer of conformations. Conformer isomerism is the phenomenon in which molecules have the same structural formula but atoms exhibit different conformations (conformers) around rotating bonds. In specific embodiments, the compounds described herein exist in a solvated form with a pharmaceutically acceptable solvent such as water or ethanol. In other embodiments, the compounds described herein exist in an unsolvated form. Solvates contain stoichiometric and non-stoichiometric amounts of solvent and can be formed during crystallization in the presence of a pharmaceutically acceptable solvent such as water or ethanol. 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 as well as solvated forms. Generally speaking, for the purposes of the compounds and methods provided herein, solvated forms are considered equivalent to unsolvated forms. Other forms in which the compounds of some embodiments may be provided include amorphous forms, milled forms, and nanoparticle forms.

[0089] Likewise, it should be understood that the compounds described herein, e.g., compounds of some embodiments, include compounds in any form described herein (e.g., pharmaceutically acceptable salts, prodrugs, crystalline forms, amorphous forms, solvated forms, enantiomeric forms, tautomeric forms, etc.).

[0090] Composition

[0091] In aspects, disclosed herein are compositions comprising one or more compounds described herein and a carrier. In some embodiments, the one or more compounds are of plant origin. In some embodiments, the one or more compounds are derived from cells. In some embodiments, the one or more compounds are synthetically produced. In some embodiments, the composition is an oral composition.

[0092] In some embodiments, the composition comprises a plant extract and a carrier, wherein the plant extract includes one or more compounds described herein. As used herein, "extract" refers to a composition containing the desired compound of interest, which is separated from other substances present in the natural source material from which the oral composition is obtained. Plant extracts can be obtained from any plant tissue, including the whole plant; plant parts, such as bud vegetative organs / structures (e.g., leaves, stems, and tubers), roots, flowers and flower organs / structures (e.g., bracts, sepals, petals, stamens, carpels, anthers, and ovules), seeds (including embryos, endosperms, and seed coats), and fruits (mature ovaries); plant tissues (e.g., vascular tissues, basic tissues, etc.); or cells (e.g., guard cells, egg cells, etc.), as well as their progeny and cultures or cell lines. In some embodiments, the extract is generally considered to be safe for human ingestion. Therefore, in certain embodiments, the extract is from an edible source. In this regard, the extract is an edible extract. The extract can be prepared by freezing, grinding, macerating, pulverizing and / or fermenting the target source material, subjecting the source material to solvent extraction, and separating insoluble matter from soluble matter. In this regard, the "extract" of the present disclosure can be a crude extract, a fractionated extract, a subfractionated extract, an isolated extract, a separated extract, an enriched extract, or a purified extract, but is not limited thereto.

[0093] In some embodiments, plant extract can be a crude extract. As used herein, "crude extract" refers to a compound or molecule that has not yet been completely separated from the component of the original composition with which it exists. In embodiments relating to fractions or subfractions, the molecule in the crude extract can be partially separated to provide a sub-crude extract containing other substances. In contrast, the term "isolated" means that the compound or molecule is substantially enriched or purified relative to its naturally occurring complex cellular environment (such as in a crude extract). When the isolated molecule is enriched or purified, absolute purity level is unimportant, and those skilled in the art can easily determine appropriate purity level according to the purposes of the material. In some cases, the isolated molecule forms a part for a composition (for example, containing a lot of other substances, such as a crude extract or a sub-crude extract), which can for example contain other components. In other cases, the isolated molecule can be purified to substantially homogeneous, for example, measured by spectrophotometry, NMR or chromatography (for example LC-MS).

[0094] Suitable solvents for the preparation of extracts include, for example, n-pentane, hexane, butane, chloroform, dichloromethane, 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 of any ratios thereof. When using the solvents listed above, the extracts obtained generally contain nonspecific fat-soluble substances. This nonspecific fat-soluble substance can be removed by a variety of processes, including "winterization," which involves cooling to a specific temperature (typically -20°C), followed by filtration or centrifugation to remove waxy ballast, extraction with subcritical or supercritical carbon dioxide or a non-polar solvent (e.g., hexane), and distillation.

[0095] In some embodiments, the plant extract comprises Eupatorium perforatum. In some embodiments, the plant extract comprises a purified or crude extract of Eupatorium 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 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, and the powder may be heated to a temperature in the range of about 30°C to 100°C to remove the oil prior to the extraction step. 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.

[0096] In some embodiments, the plant extract comprises ginger. In some embodiments, the plant extract comprises a purified or crude extract of ginger. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0097] In some embodiments, the plant extract comprises Sitka spruce. In some embodiments, the plant extract comprises a purified or crude extract of Sitka spruce. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaves. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flowers. In some embodiments, the extract can be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0098] In some embodiments, the plant extract includes Viburnum zedoaria. In some embodiments, the plant extract includes a purified or crude extract of Viburnum zedoaria. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can be heated to a temperature in the range of about 30°C to 100°C to remove the oil before performing the extraction step. In some embodiments, the plant extract includes 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-methyldavidioside. 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.

[0099] 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 can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder and the powder heated to a temperature in the range of about 30°C to 100°C to remove the oil prior to performing the extraction step. In some embodiments, the plant extract comprises 3,4′,5,7-tetrahydroxyflavone. In some embodiments, the plant extract comprises Compound 12.

[0100] In some embodiments, the plant extract comprises sunflower. In some embodiments, the plant extract comprises a purified or crude extract of sunflower. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0101] In some embodiments, the plant extract comprises lettuce. In some embodiments, the plant extract comprises a purified or crude extract of lettuce. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0102] In some embodiments, the plant extract comprises Echinops chinensis. In some embodiments, the plant extract comprises a purified or crude extract of Echinops chinensis. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0103] In some embodiments, the plant extract comprises Aucklandia lappa. In some embodiments, the plant extract comprises a purified or crude extract of Aucklandia lappa. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder is then heated to a temperature in the range of about 30°C to 100°C to remove the oil before performing the extraction step.

[0104] In some embodiments, the plant extract comprises Aucklandia lappa. In some embodiments, the plant extract comprises a purified or crude extract of Aucklandia lappa. 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, and the powder may then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0105] 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 can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0106] In some embodiments, the plant extract comprises Inula officinalis. In some embodiments, the plant extract comprises a purified or crude extract of Inula officinalis. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0107] In some embodiments, the plant extract comprises laurel. In some embodiments, the plant extract comprises a purified or crude extract of laurel. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0108] In some embodiments, the plant extract comprises Momordica charantia. In some embodiments, the plant extract comprises a purified or crude extract of Momordica charantia. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0109] In some embodiments, the plant extract comprises patchouli. In some embodiments, the plant extract comprises a purified or crude extract of patchouli. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0110] In some embodiments, the plant extract comprises chicory. In some embodiments, the plant extract comprises a purified or crude extract of chicory. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0111] 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 can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder and the powder can be heated to a temperature in the range of about 30°C to 100°C to remove the oil before performing the extraction step.

[0112] In some embodiments, the plant extract comprises barley. In some embodiments, the plant extract comprises a purified or crude extract of barley. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0113] In some embodiments, the plant extract comprises common wheat. In some embodiments, the plant extract comprises a purified or crude extract of common wheat. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaves. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flowers. In some embodiments, the extract can be derived directly from the roots. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0114] In some embodiments, the plant extract comprises pitcherwort. In some embodiments, the plant extract comprises a purified or crude extract of pitcherwort. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaves. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flowers. In some embodiments, the extract can be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder and the powder can then be heated to a temperature in the range of about 30°C to 100°C to remove the oil prior to performing the extraction step.

[0115] In some embodiments, the plant extract comprises tricholoma. In some embodiments, the plant extract comprises a purified or crude extract of tricholoma. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder and the powder can be heated to a temperature in the range of about 30°C to 100°C to remove the oil before performing the extraction step.

[0116] 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 can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30°C to 100°C to remove the oil prior to performing the extraction step.

[0117] In some embodiments, the plant extract comprises tea. In some embodiments, the plant extract comprises a purified or crude extract of tea. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before proceeding to the extraction step.

[0118] In some embodiments, the plant extract comprises barley. In some embodiments, the plant extract comprises a purified or crude extract of barley. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0119] In some embodiments, the plant extract comprises millet. In some embodiments, the plant extract comprises a purified or crude extract of millet. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaves. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flowers. In some embodiments, the extract can be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before proceeding to the extraction step.

[0120] In some embodiments, the plant extract comprises corn. In some embodiments, the plant extract comprises a purified or crude extract of corn. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaves. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flowers. In some embodiments, the seeds, leaves, and / or flowers can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0121] 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 can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder is then heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0122] 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 can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaves. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flowers. In some embodiments, the extract can be derived directly from the roots. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder and the powder can then be heated to a temperature in the range of about 30°C to 100°C to remove the oil before performing the extraction step.

[0123] In some embodiments, the plant extract comprises Puget Sound gumweed. In some embodiments, the plant extract comprises a purified or crude extract of Puget Sound gumweed. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaves. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flowers. In some embodiments, the extract can be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0124] In some embodiments, the plant extract comprises Lobelia chinensis. In some embodiments, the plant extract comprises a purified or crude extract of Lobelia chinensis. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0125] In some embodiments, the plant extract comprises peanuts. In some embodiments, the plant extract comprises a purified or crude extract of peanuts. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaves. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flowers. In some embodiments, the extract can be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0126] In some embodiments, the plant extract comprises Nepenthes indicus. In some embodiments, the plant extract comprises a purified or crude extract of Nepenthes indicus. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0127] In some embodiments, the plant extract comprises Selaginella truncatula. In some embodiments, the plant extract comprises a purified or crude extract of Selaginella truncatula. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder and the powder can be heated to a temperature in the range of about 30°C to 100°C to remove the oil before performing the extraction step.

[0128] In some embodiments, the plant extract comprises Selaginella truncatula. In some embodiments, the plant extract comprises a purified or crude extract of Selaginella truncatula. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder and the powder can be heated to a temperature in the range of about 30°C to 100°C to remove the oil before performing the extraction step.

[0129] In some embodiments, the plant extract comprises Taxus chinensis. In some embodiments, the plant extract comprises a purified or crude extract of Taxus chinensis. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaves. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flowers. In some embodiments, the extract can be derived directly from the roots. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder and the powder can then be heated to a temperature in the range of about 30°C to 100°C to remove the oil before performing the extraction step.

[0130] In some embodiments, the plant extract comprises Acorus calamus. In some embodiments, the plant extract comprises a purified or crude extract of Acorus calamus. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0131] 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 can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0132] In some embodiments, the plant extract comprises Artemisia seaweed. In some embodiments, the plant extract comprises a purified or crude extract of Artemisia seaweed. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder is then heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0133] 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 can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0134] In some embodiments, the plant extract comprises Polygonum multiflorum. In some embodiments, the plant extract comprises a purified or crude extract of Polygonum multiflorum. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0135] In some embodiments, the plant extract comprises upland cotton. In some embodiments, the plant extract comprises a purified or crude extract of upland cotton. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder is then heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0136] 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 can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaves. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flowers. In some embodiments, the extract can be derived directly from the roots. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder and the powder can then be heated to a temperature in the range of about 30°C to 100°C to remove the oil before performing the extraction step.

[0137] 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 can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0138] In some embodiments, the plant extract comprises Musa acuminata. In some embodiments, the plant extract comprises a purified or crude extract of Musa acuminata. 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, and the powder may then be heated to a temperature in the range of about 30°C to 100°C to remove the oil prior to performing the extraction step.

[0139] In some embodiments, the plant extract comprises wild rice. In some embodiments, the oral composition comprises an extract of wild rice. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0140] In some embodiments, the plant extract comprises rice. In some embodiments, the plant extract comprises a purified or crude extract of rice. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0141] In some embodiments, the plant extract comprises Spanish cork oak. In some embodiments, the plant extract comprises a purified or crude extract of Spanish cork oak. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0142] In some embodiments, the plant extract comprises potato. In some embodiments, the plant extract comprises a purified or crude extract of potato. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0143] In some embodiments, the plant extract comprises valerian. In some embodiments, the plant extract comprises a purified or crude extract of valerian. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to performing the extraction step.

[0144] In some embodiments, the plant extract comprises grapes. In some embodiments, the plant extract comprises a purified or crude extract of grapes. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before proceeding to the extraction step.

[0145] 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 can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0146] In some embodiments, the plant extract comprises soybeans. In some embodiments, the plant extract comprises a purified or crude extract of soybeans. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaves. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil before performing the extraction step.

[0147] In some embodiments, the plant extract comprises Switchgrass Pioneer cultivar In some embodiments, the plant extract comprises Purified or crude extracts of switchgrass pioneer cultivar 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, and the powder may then be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to proceeding to the extraction step.

[0148] In some embodiments, the plant extract comprises Populus trichocarpa. In some embodiments, the plant extract comprises a purified or crude extract of Populus trichocarpa. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaves. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flowers. In some embodiments, the extract can be derived directly from the roots. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder and the powder can then be heated to a temperature in the range of about 30°C to 100°C to remove the oil prior to performing the extraction step.

[0149] In some embodiments, the plant extract includes Arugula inflata ( Eruca vesicaria). In some embodiments, the plant extract comprises a purified or crude extract of Arugula inflata. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can be heated to a temperature in the range of about 30°C to 100°C to remove the oil before performing the extraction step. In some embodiments, the plant extract comprises prop-2-enoic acid [(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) ester. In some embodiments, the plant extract comprises Compound 22.

[0150] In some embodiments, the plant extract includes Glehnia littoralis ( Gynura procumbens ). In some embodiments, the plant extract comprises a purified or crude extract of Glehnia littoralis. 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, and the powder may be heated to a temperature in the range of about 30°C to 100°C to remove the oil prior to performing the extraction step. 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]oxyoxan-2-yl]oxy-3,5-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one. In some embodiments, the plant extract includes Compound 21.

[0151] In some embodiments, the plant extract includes Psoralea corylifolia ( Clausena excavata). In some embodiments, the plant extract comprises a purified or crude extract of Psoralea corylifolia. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaves. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flowers. In some embodiments, the extract can be derived directly from the roots. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can be heated to a temperature in the range of about 30°C to 100°C to remove the oil before performing the extraction step. 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]oxyoxan-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.

[0152] In some embodiments, the plant extract includes guava ( Psidium guajava ). In some embodiments, the plant extract comprises a purified or crude extract of guava. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers and / or roots can be ground into a powder, and the powder can be heated to a temperature in the range of about 30°C to 100°C to remove the oil before performing the extraction step. In some embodiments, the plant extract comprises 3-[(2S,3R,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)oxan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one. In some embodiments, the plant extract comprises Compound 27.

[0153] In some embodiments, the plant extract includes Senna ( Senna alexandrinaIn some embodiments, the plant extract comprises a purified or crude extract of senna. 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, and the powder may be heated to a temperature in the range of about 30° C. to 100° C. to remove the oil prior to the extraction step. 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 includes Compound 23. In some embodiments, the plant extract includes Compound 26.

[0154] In some embodiments, the plant extract includes Coleus brevis. In some embodiments, the plant extract includes a purified or crude extract of Coleus brevis. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the leaf. In some embodiments, the extract can be derived directly from the whole seed. In some embodiments, the extract can be derived directly from the flower. In some embodiments, the extract can be derived directly from the root. In some embodiments, the seeds, leaves, flowers, and / or roots can be ground into a powder, and the powder can be heated to a temperature in the range of about 30°C to 100°C to remove the oil before performing the extraction step. In some embodiments, the plant extract includes 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 includes 3,6-dimethoxyapigenin. In some embodiments, the plant extract includes Compound 30.

[0155] In some embodiments, the oral composition comprises extracts from one or more plant sources. In some embodiments, the oral composition comprises extracts from two or more plant sources. In some embodiments, the oral composition comprises extracts from three or more plant sources.

[0156] In some embodiments, the extracts described herein include juices, infusions, and fermentation residues.The products of fermenting plant-derived extracts or processed fractions thereof can be used in consumer product compositions, such as health-promoting compositions or tonics for humans and animals.

[0157] 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%, 99% w / w, or one or more compounds of the disclosure or extracts including the aforementioned values ​​and / or the range across the aforementioned values. In some embodiments, the composition comprises about 0.1% to about 10% of one or more compounds or extracts described herein. In some embodiments, the composition comprises about 0.1% to about 5% of one or more compounds or extracts described herein. In some embodiments, the composition comprises about 1% to about 10% of one or more compounds or extracts described herein. In some embodiments, when one or more compounds of the present disclosure or extracts are provided or administered to humans and animals as medicines, nutritional medicines or dietary supplements, they can be administered alone or in the form of a composition containing, for example, 0.1% to 99% active ingredient and an acceptable carrier. In some embodiments, the one or more compounds of the present disclosure or extracts provided or administered can be 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%, 99% w / w, or include the aforementioned values ​​and / or the range across the aforementioned values. In some embodiments, plant extracts described herein include one or more compounds selected from Table A. In some embodiments, compositions described herein include one or more compounds selected from Table A. In some embodiments, one or more compounds selected from Table A include Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25, Compound 26, Compound 27, Compound 28, Compound 29, Compound 30, Compound 31, Compound 33, Compound 34, Compound 35, or a combination thereof.

[0158] In some embodiments, the composition can include one or more compounds described herein and a suitable carrier or excipient. In some embodiments, the ratio of one or more compounds described herein can be from about 10:1 to about 1:10, or include and / or span a range of the aforementioned values. In some embodiments, the ratio of one or more compounds described herein can 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 composition comprises one or more compounds described in Table A. In some embodiments, one or more compounds selected from Table A include Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25, Compound 26, Compound 27, Compound 28, Compound 29, Compound 30, Compound 31, Compound 33, Compound 34, Compound 35, or a combination thereof.

[0159] 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 intake. In some embodiments, an acceptable carrier is a pharmaceutically acceptable carrier. In some embodiments, an acceptable carrier is a food grade carrier. In some embodiments, 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 that participates in carrying or transporting the subject compound from one organ or body part to another organ or body part, such as a liquid or solid filler, diluent, excipient, manufacturing aid (e.g., lubricant, talc, magnesium stearate, calcium stearate or zinc stearate, or stearic acid) or solvent encapsulation material. Each carrier should be compatible with the other ingredients in the formulation and will not cause harm to the subject. Some examples of substances that can serve 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 hypromellose; (4) tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients such as cocoa butter, carnauba wax, beeswax, paraffin, candelilla wax, shellac wax, rice wax, and suppository wax; (9 ) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; (10) glycols, such as propylene glycol and glycerol (glycerol); (11) polyols, such as glycerol, 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) ethanol; (20) pH buffer solutions; (21) polyesters, polycarbonates, and / or polyanhydrides; (22) lipids and / or phospholipids; and (23) other nontoxic compatible substances used 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), buffer substances (such as phosphates), glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts, or electrolytes (such as protamine sulfate), disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silicon dioxide, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, PEG, maltodextrin, calcium carbonate, dicalcium phosphate, tricalcium phosphate, microcrystalline cellulose, dextrose, rice flour, magnesium stearate, stearic acid, cross-linked sodium carboxymethylcellulose, sodium starch glycolate, crospovidone, sucrose, vegetable gums, lactose, methylcellulose, povidone, carboxymethylcellulose, corn starch, and mixtures thereof. Other examples of pharmaceutically acceptable carriers can be found, for example, in AN'EL'S PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY SYSTEMS. ( In some embodiments, the carrier comprises about 0.5% to about 80% (w / w) of the composition. In some embodiments, the carrier comprises 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 inclusive of, between, and / or across the foregoing values.

[0160] In some embodiments, the oral compositions may further comprise a preservative. In some embodiments, the amount of the preservative may be 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 values ​​inclusive and / or ranges across these values. In some embodiments, the preservative can be, but is not limited to, selected from the group consisting of sodium benzoate, methylparaben, propylparaben, sodium nitrite, sulfur dioxide, sodium sorbate, ascorbic acid, tocopherol, calcium propionate, citric acid, sorbic acid, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), alcohol (such as ethanol), rosemary extract and potassium sorbate. Other suitable preservatives include, but are not limited to, edetate (also known as ethylenediaminetetraacetic acid salt or EDTA salt, such as disodium EDTA).

[0161] In some embodiments, oral compositions can also include sweetener.In some embodiments, the amount of sweetener can be 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 include aforementioned value and / or the scope across aforementioned value.In some embodiments, sweetener can include natural sweetener.In some embodiments, sweetener can include synthetic sweetener. Non-limiting examples of sweeteners include sucrose, glucose, maltose, dextrin, dried 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.

[0162] In some embodiments, oral compositions can also include flavorings.In some embodiments, the amount of flavorings can be 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 include aforementioned value and / or the scope across aforementioned value.In some embodiments, flavorings can include natural flavors or artificial flavors.In a specific embodiment, flavorings include essential oils, such as oil, peppermint oil, spearmint oil, other peppermint oils, clove oil, cinnamon oil, wintergreen oil, bay oil, thyme oil, cedar leaf oil, nutmeg oil, allspice oil, sage oil, mace oil and almond oil deriving from plant or fruit. In another specific embodiment, the flavoring agent comprises a plant extract or fruit essence, such as apple, banana, watermelon, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot and mixtures thereof. In another specific embodiment, the flavoring agent comprises a citrus flavor, such as an extract, essence or oil of lemon, lime, orange, mandarin orange, grapefruit, citron or kumquat.

[0163] In some embodiments, the oral compositions may further comprise a colorant. In some embodiments, the amount of the colorant may be 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 values ​​inclusive and / or ranges thereof.

[0164] In some embodiments, oral compositions can also include at least one additive.In some embodiments, the amount of additive can be 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 include aforementioned value and / or the scope across aforementioned value.In some embodiments, at least one additive can be an emulsifier.In some embodiments, additive can include one or more vitamins.In some embodiments, additive can include one or more mineral substances.In some embodiments, additive can include stabilizer.

[0165] In some embodiments, the compositions described herein may comprise two or more compounds of Formula (I) (IA) (IB) (II) (IIB), or (III) (III). In some embodiments, the ratio of the two or more compounds described herein may be from about 10:1 to about 1:10, inclusive and / or ranges thereof. In some embodiments, the ratio of two or more compounds described herein can 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, two or more compounds can be selected from Table A, their salts, or isomers. In some embodiments, two or more compounds selected from Table A include Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25, Compound 26, Compound 27, Compound 28, Compound 29, Compound 30, Compound 31, Compound 33, Compound 34, Compound 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 comprises Compound 20. In some embodiments, one of the two or more compounds comprises Compound 21. In some embodiments, one of the two or more compounds comprises 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 include at least two of Compound 14, Compound 22, Compound 23, Compound 26, and Compound 30. In some embodiments, the ratio of the two or more compounds is from about 10:1 to about 1:10. In some embodiments, the ratio of the two or more compounds is from about 5:1 to about 1:5. In some embodiments, the ratio of the two or more compounds is from about 2.5:1 to about 2:1. In some embodiments, the ratio of the two or more compounds is from about 2.5:1 to about 1:2.5. In some embodiments, the ratio of the two or more compounds is from about 5:1. In some embodiments, the ratio of the two or more compounds is from about 4:1. In some embodiments, the ratio of the two or more compounds is from about 3:1. In some embodiments, the ratio of the two or more compounds is from about 2:1. In some embodiments, the ratio of the two or more compounds is from about 1:1. In some embodiments, the ratio of the two or more compounds is from about 1:2. In some embodiments, the ratio of the two or more compounds is from about 1:3. In some embodiments, the ratio of the two or more compounds is about 1:4. In some embodiments, the ratio of the two or more compounds is about 1:5. In some embodiments, the oral composition comprises a compound of Formula (III), but does not comprise a compound selected from the group consisting of Compound 30, Compound 31, or a combination thereof.In some embodiments, the oral composition comprises two or more compounds of Formula (I), Formula (IA), Formula (IB), Formula (II), or Formula (III), but does not comprise a compound selected from the group consisting of Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25, Compound 26, Compound 27, Compound 28, Compound 29, Compound 30, Compound 31, Compound 33, Compound 34, Compound 35, or a combination thereof. In some embodiments, the oral composition consists essentially of Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25, Compound 26, Compound 27, Compound 28, Compound 29, Compound 30, Compound 31, Compound 33, Compound 34, Compound 35, or a combination thereof, which do not bind to lignocellulosic matter. In some embodiments, the oral composition comprises two or more compounds selected from Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25, Compound 26, Compound 27, Compound 28, Compound 29, Compound 30, Compound 31, Compound 33, Compound 34, Compound 35, or a combination thereof, with the proviso that the two or more compounds do not bind to lignin, cellulose, and / or pectin in the oral composition. In some embodiments, the oral composition comprises two or more compounds selected from Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25, Compound 26, Compound 27, Compound 28, Compound 29, Compound 30, Compound 31, Compound 33, Compound 34, Compound 35, or a combination thereof, with the proviso that the two or more compounds are not from extracts of natural sources or are not extracted from natural sources (e.g., plants).

[0166] In some embodiments, oral compositions can be essentially composed of one or more compounds described herein that are not bound to lignocellulosic materials. Lignocellulosic materials refer to composite materials that are primarily composed of lignin, cellulose, and hemicellulose. These are naturally occurring polymers in the cell walls of plants. Lignocellulosic materials are characterized by their rigid structure, high strength, and resistance to decomposition. This material is typically derived from the inedible parts of wood, grass, and plants. In some embodiments, the composition does not include lignin, cellulose, and / or pectin. In some embodiments, the composition does not include extracts from natural sources.

[0167] In some embodiments, the oral composition comprises a compound of formula (I) selected from the group consisting of compound 12, compound 13, compound 14, compound 15, compound 20, compound 21, compound 22, compound 23, compound 24, compound 25, compound 26, compound 27, compound 28, compound 29, compound 33, compound 34, and compound 35. In some embodiments, the oral composition comprises a compound of formula (I) selected from the group consisting of compound 14, compound 22, compound 23, and compound 26. In some embodiments, the oral composition comprises a compound of formula (I) selected from the group consisting of compound 22 and compound 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 compound 16, compound 17, compound 18, and compound 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 compound 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 comprise a compound selected from the group consisting of compound 12, compound 13, compound 14, compound 15, compound 20, compound 21, compound 22, compound 23, compound 24, compound 25, compound 26, compound 27, compound 28, compound 29, compound 33, compound 34, compound 35, or a combination thereof. In some embodiments, the oral composition comprises a compound of formula (II), but does not comprise a compound selected from the group consisting of compound 16, compound 17, compound 18, compound 19, or a combination thereof. In some embodiments, the oral composition comprises a compound of formula (III), but does not comprise a compound selected from the group consisting of compound 30, compound 31, or a combination thereof. In some embodiments, the oral composition comprises one or more compounds of Formula (I), Formula (IA), Formula (IB), Formula (II), or Formula (III), but does not comprise a compound selected from the group consisting of Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25, Compound 26, Compound 27, Compound 28, Compound 29, Compound 30, Compound 31, Compound 33, Compound 34, Compound 35, or a combination thereof.In some embodiments, the oral composition consists essentially of Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25, Compound 26, Compound 27, Compound 28, Compound 29, Compound 30, Compound 31, Compound 33, Compound 34, Compound 35, or a combination thereof, which do not bind to lignocellulosic matter. In some embodiments, the oral composition comprises one or more compounds selected from Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25, Compound 26, Compound 27, Compound 28, Compound 29, Compound 30, Compound 31, Compound 33, Compound 34, Compound 35, or a combination thereof, with the proviso that the one or more compounds do not bind to lignin, cellulose, and / or pectin in the oral composition. In some embodiments, the oral composition comprises one or more compounds selected from Compound 12, Compound 13, Compound 14, Compound 15, Compound 16, Compound 17, Compound 18, Compound 19, Compound 20, Compound 21, Compound 22, Compound 23, Compound 24, Compound 25, Compound 26, Compound 27, Compound 28, Compound 29, Compound 30, Compound 31, Compound 33, Compound 34, Compound 35, or a combination thereof, with the proviso that the one or more compounds are not derived from an extract of a natural source or are not extracted from a natural source (e.g., a plant).

[0168] preparation

[0169] Aspects of the present disclosure relate to preparations comprising one or more compounds described herein. In some embodiments, substantially pure compounds or extracts comprising one or more compounds of the present disclosure can be combined with a carrier and provided in any suitable form for subject intake, provided to a subject or administered to a subject. In some embodiments, one or more compounds or extracts comprising one or more compounds are added to consumer products as exogenous ingredients or additives. Suitable consumer product forms include, but are not limited to, dietary supplements, food ingredients or additives, food products, medical foods, nutritional medicines or pharmaceutical compositions. In some embodiments, the one or more compounds or extracts comprising one or more compounds are provided in liquid, granular or powder form. In some embodiments, the preparation can be a food product.

[0170] Compositions comprising plant extracts or compounds of the present disclosure can be combined with a carrier and provided in any suitable form for ingestion or administration to a subject. In this regard, plant extracts or compounds are added to consumer products as exogenous ingredients or additives. Suitable consumer product forms include, but are not limited to, dietary supplements, food ingredients or additives, medical foods, nutritional medicines, or pharmaceutical compositions. In some embodiments, plant extracts or compounds are provided in the form of liquids or powders.

[0171] Food ingredient or additive is intended to become the component of any food or otherwise affect the edible substance (including any substance intended for production, manufacture, packaging (packing), processing, preparation, treatment, packaging (packaging), transportation or preservation of food) of the feature of any food directly or indirectly. Food product, particularly functional food, is the food that strengthens or supplements nutrients during processing, to include additional supplementary nutrients and / or beneficial ingredients. Food product according to the present disclosure can be, for example, in the form of butter, margarine, sweet or savory spreads, condiments, biscuits, health bars (health bar), bread, cake, cereals, candy, sweets, soup, milk, yogurt or fermented dairy products, cheese, juice and vegetable beverages, fermented beverages, milk shakes, flavored water, tea, oil or any other suitable food. In some embodiments, food product is a fully natural food product, wherein the concentration of the compound has been enriched to the level of providing the compound of effective amount by specific harvest and food production and processing method. In some embodiments, food product includes one or more compounds described herein and a fiber source. In some embodiments, food product includes one or more compounds described herein. In some embodiments, the food product is a food bar. In some embodiments, the food bar comprises about 0.01% to about 20% (w / w) of one or more compounds described herein. In some embodiments, the food bar comprises 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 about 0.01% to about 20% (w / w) of one or more compounds described herein. In some embodiments, the food crisp comprises about 0.1% to about 10% (w / w) of one or more compounds described herein.

[0172] Compounds, compositions and extracts disclosed herein can be prepared as nutritional preparations, such as food, including medical or functional foods."Medical or functional foods" are defined as being taken in as part of a daily diet, but have been shown to have, in addition to basic nutritional functions, physiological benefits and / or reduce the risk of disease or illness (such as chronic diseases). For example, but not limited to, medical foods and functional foods can include 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 substances. Dietary supplements can also be incorporated into food (such as functional foods designed to promote health or prevent disease or symptom). If the composition is applied in the form of a pharmaceutical preparation, the composition can be applied to the patient as a prevention or treatment in any of a variety of ways. In some embodiments, the composition described herein can be applied alone or in combination with other additives or medicaments, and can be combined with their physiologically acceptable carriers. The effective dosage and method of administration of a particular formulation and the target may vary depending on the individual subject, the stage of the disease or condition, and other factors known to those skilled in the art. For pharmaceutical and nutraceutical formulations, the concentration of the subject composition may be monitored (e.g., plasma levels may be monitored) during treatment to ensure that the desired level is maintained.

[0173] In some embodiments, food products include carbohydrates. A variety of carbohydrates are used in food products, such as various sugars and starches. Carbohydrates are an important source of energy for the human body, including complex carbohydrates (such as whole grains and vegetables) and simple carbohydrates (such as sugars and refined grains). A variety of common carbohydrates are used in food products, including starch, sugar, fructose, maltodextrin, dextrose, corn syrup, oligosaccharides, cellulose, complex carbohydrates, such as inulin that can be added to processed foods as a prebiotic fiber. According to the present disclosure, the concentration of carbohydrates can vary according to the intended use of the product. In some embodiments, carbohydrates can account for about 1 weight % to about 95 weight % of the food product. In some embodiments, carbohydrates can account for about 1 weight % to about 95 weight % of the food product. In some embodiments, the food product can contain carbohydrates within high and low ranges 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 a range including, between, and / or across the foregoing values.

[0174] In some embodiments, food products can include sugar.Sugar, such as high fructose corn syrup, sucrose, glucose syrup, dextrose and other sweeteners, are often added to processed foods to make them more palatable. In addition, sugar alcohol or maltodextrin can also be added to food products to reduce caloric content and / or enhance the nutritional composition of the product. In some embodiments, food products can include one or more sugars, even if these sugars can not be fully digested, they will be slowly or incompletely digested by the human body. These sugars can include isomaltose, panose (panose) and a degree of polymerization that is four or higher branched oligomers. Other non-limiting examples of sugar include sucrose, HFCS, fructose, brown sugar (can be partially or completely refined), powdered sugar (also referred to as powdered sugar), high fructose corn syrup, honey, molasses, maple syrup, agave nectar, coconut sugar, date sugar, fruit juice concentrate, maltodextrin, dextrose, glucose syrup, maple syrup, molasses and lactose. According to the present disclosure, the concentration of sugar can vary according to the intended use of the product. In some embodiments, sugar can account for about 1% to about 95% by weight of the food product. In some embodiments, the sugar component accounts for about 2% to about 10% by weight of the composition. In some embodiments, sugar can account for about 1% to about 95% by weight of the food product. In some embodiments, the food product can be included in a carbohydrate independently selected from the group consisting 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 a range including, between, and / or across values.

[0175] In some embodiments, food products include a fiber source. In some embodiments, food products include about 5% to about 30% (w / w) fiber. In some embodiments, food products include at least 10% fiber. In some embodiments, food products include at least 15% fiber. In some embodiments, food products include at least 20% fiber. In some embodiments, food products include at least 30% fiber. In some embodiments, fiber can be selected from psyllium husk, inulin, beta-glucan, acacia fiber, pectin, wheat dextrin, cellulose, fructooligosaccharide, guar gum, fruit fiber or a combination thereof. In some embodiments, fiber is soluble dietary fiber.

[0176] In some embodiments, food products may include protein. Depending on the product, the protein included may be within a certain concentration range. Protein sources may include soy protein, soy flour, soy protein isolate, whey protein isolate, casein, gelatin, soy protein isolate, soy protein concentrate, egg white albumin or egg white, wheat protein concentrate, soy protein concentrate, and mixtures thereof. In some embodiments, meat products (e.g., beef jerky, sausage, or meatballs) may include protein as a primary ingredient. The concentration range of the included protein may be from about 10% to about 25% of the total ingredients. In dairy products such as cheese, yogurt, or milk, proteins such as casein or whey may be the primary ingredients. The concentration range of the included protein may be from about 3% to about 15% of the total ingredients. In plant products such as tofu, tempeh, or gluten, proteins from soybeans, peas, beans, or wheat may be the primary ingredients. The concentration range of the included protein may be from about 10% to about 25% of the total ingredients. In energy bars and protein bars, proteins such as whey or soybeans, or any protein according to the present disclosure, may be added to provide a protein source. In some embodiments, the protein of the present invention can be included in the protein of the present invention.The concentration range of protein included can be about 10% to about 25% of total composition.According to the disclosure, the concentration of protein can change according to the intended use of product.In some embodiments, protein can account for food products about 1 % by weight to about 95 % by weight.In some embodiments, protein can account for food products about 1 % by weight to about 95 % by weight.In some embodiments, food products can be included in the protein independently selected from following high value and low value scope: about 1%, 3%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or comprise aforementioned value, between aforementioned value and / or the scope across aforementioned value.

[0177] In some embodiments, food products can include starch.In some embodiments, food products can comprise the starch component of the amount that is enough to provide about 5% to 45% or about 10% to 30% or about 15% to 25% starch in food products in addition.Starch component can not only comprise the cereal flour or other particles of pure interpolation, but also can comprise any part that is rich in starch provided by other compositions such as oat bran or soy protein.In some embodiments, starch can comprise the starch or cereal flour component of any conventional use, for instant cereals.Exemplary suitable cereals that are rich in starch comprise the cereal flour from most of cereal kernels, comprise wheat, rice, corn (maize), oats, barley, rye or the starch part separated from cereal flower, comprise for example corn starch, wheat starch, rice starch and various processed starch, comprise pregelatinized starch and / or modified starch.

[0178] In some embodiments, the food product may include flour. According to the present invention, several types of flour can be used. For example, types of flour commonly used in food products include all-purpose flour (which, like most other flours, may contain protein), whole wheat flour, bread flour, cake flour, pastry flour, self-raising flour, and gluten-free flour. According to the present disclosure, the concentration of flour can vary depending on the intended use of the product. For example, in baked goods such as bread, cakes, and cookies, flour is typically the main ingredient and its concentration can range from 50% to 100% of the total dry ingredients. In soups and sauces, flour is typically used as a thickener and its concentration can range from 1% to 5% of the total ingredients. Batter and breading: In fried foods such as chicken or fish, flour is typically used as part of the batter or breading and its concentration can range from 20% to 50% of the total dry ingredients. In snack foods such as cookies and potato chips, the concentration of flour included can range from 30% to 70% of the total ingredients. In some embodiments, flour can comprise approximately 1% to approximately 95% by weight of the food product. In some embodiments, flour can comprise approximately 1% to approximately 95% by weight of the food product. In some embodiments, the food product may comprise flour within a high and low range 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 a range including, between, and / or across the foregoing values.

[0179] In some embodiments, a food product may include fat. In some embodiments, a food product may include oil. In some embodiments, a food product may include one or more fats or oils. According to the present disclosure, several types of fats may be used. 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, the concentration of fat included may range from 10% to 30% of the total ingredients. In some embodiments, such as in sauces and dressings, fats such as olive oil or mayonnaise are often used to provide flavor and texture. In some embodiments, the concentration of fat included may range 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 the concentration of fat included may range from 30% to 60% of the total ingredients. In snack foods such as potato chips and crackers, fats such as vegetable oil or palm oil are often used to provide flavor and texture. In some embodiments, the concentration range of the fat included can be 10% to 30% of total composition.In some embodiments, fat can account for food product approximately 1 % by weight to approximately 95 % by weight.In some embodiments, fat can account for food product approximately 1 % by weight to approximately 95 % by weight.In some embodiments, food product can be included in the fat independently selected from following high value and low value scope: approximately 1%, 3%, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or comprise aforementioned value, between aforementioned value and / or across the scope of aforementioned value.

[0180] In some embodiments, food products can include one or more additional ingredients. If desired, disclosed food products can also include multiple materials designed to improve its attractive in appearance or nutritional quality. These adjuvant materials can include vitamins and / or mineral fortifiers, pigments, flavorings, sweeteners and their mixtures. Exact ingredient concentrations may vary. However, generally speaking, these materials can each account for approximately 0.01% to approximately 5%, or approximately 0.1% to 2% of the food product dry weight. A particularly useful material is table salt. In some embodiments, salt accounts for approximately 0.1% to 5%, or approximately 0.5% to 4.0% of the food product.

[0181] In some embodiments, the food product is derived from a plant. In some embodiments, the food product is a solid food. In some embodiments, the food product is a semi-solid food. In some embodiments, the food product is an expanded product, a baked product, a pressed cake, a prepared food, a food bar, a cereal food, a crisp, or a spread.

[0182] Dietary supplements are products for oral use that contain compounds or extracts of the present disclosure and are intended to supplement the diet. Nutraceuticals are products derived from food sources that, in addition to the basic nutritional value in food, can also provide additional health benefits. A pharmaceutical composition is defined as any component in a pharmaceutical product that is intended to provide pharmacological activity or other direct effects in the diagnosis, cure, relief, treatment or prevention of a disease, or to affect the structure and function of the body of the human body or other animals. Dietary supplements, nutraceuticals, and pharmaceutical compositions can be in the form of a variety of capsules, tablets, coated tablets, pills, capsules, pills, granules, softgels, soft gelatin capsules, liquids, powders, emulsions, suspensions, elixirs, syrups, and any other suitable forms 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 the form of liquids. 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 the form of liquids. In some embodiments, the compositions described herein are provided as medicines. In some embodiments, the medication is provided as a capsule, tablet, powder, or in liquid form.

[0183] The pharmaceutical compositions disclosed herein can be manufactured in a manner known per se, for example by means of conventional mixing, dissolving, granulating, dragee manufacturing, pulverizing, emulsifying, encapsulating, entrapping or tableting processes. In addition, the amount of active ingredient contained can effectively achieve its intended purpose. Many compounds used in the pharmaceutical combinations disclosed herein can be provided in the form of salts with pharmaceutically compatible counterions.

[0184] There are a variety of techniques for administering compounds, salts, and / or compositions 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 injections. In some embodiments, the compounds described herein, including compounds described herein, or pharmaceutically acceptable salts thereof, can be administered orally. In some embodiments, the compounds described herein, including compounds of formula (I), compounds of formula (IA), compounds of formula (IB), compounds of formula (II), compounds of formula (III), or salts thereof, can be administered orally. In some embodiments, the compounds described herein, including compounds of formula (I), compounds of formula (IA), compounds of formula (IB), compounds of formula (II), compounds of formula (III), or salts thereof, can be provided in a form for oral ingestion.

[0185] Compounds, salts, and / or compositions can also be administered in a local rather than systemic manner, for example, by direct injection or implantation of the compound into the affected area, typically provided or administered in the form of a depot or sustained-release formulation. Furthermore, the compound can be administered via a targeted drug delivery system, such as liposomes coated with tissue-specific antibodies. The liposomes will be targeted to and selectively taken up by an organ. For example, for respiratory diseases or disorders, intranasal or pulmonary delivery may be necessary.

[0186] If desired, oral compositions may be present in a package or dispenser device that may contain one or more unit dosage forms containing the active ingredient. The package may, for example, comprise metal or plastic foil, such as a blister pack. The package or dispenser device may be accompanied by instructions for administration. The package or dispenser may also be accompanied by a notice associated with the container in a form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, reflecting the form of the drug approved by the agency for human or veterinary administration. For example, such a notice may be a prescription drug label approved by the U.S. Food and Drug Administration, or an approved product insert. Compositions comprising the compounds and / or salts described herein formulated in a compatible pharmaceutical excipient may also be prepared, placed in an appropriate container, and labeled for use in treating a specified condition.

[0187] Compound, salt and / or pharmaceutical composition can be provided to the doctor or other healthcare professional in the form of a medicine box. A medicine box is a package containing a container containing a compound in the form of a suitable pharmaceutical composition, and instructions for administering the pharmaceutical composition to the subject. The medicine box can also optionally contain one or more additional therapeutic agents. The medicine box can also contain separate doses of the compound or pharmaceutical composition for continuous or sequential administration. The medicine box can optionally contain one or more diagnostic tools and instructions for use. The medicine box can contain a suitable delivery device, such as a syringe, etc., and instructions for administering the compound and any other therapeutic agent. The medicine box can optionally contain instructions for storage, redissolution (if applicable) and administration of any or all therapeutic agents included. The medicine box can include multiple containers, reflecting the number of administrations administered to the subject.

[0188] In some embodiments, the oral compositions described herein are administered in a dosage range of about 0.1-200 mg / kg body weight. In some embodiments, the oral compositions described herein are administered in a dosage range of about 0.1-1 mg, 0.5-1 mg, 0.1-10 mg, 0.5-10 mg, 1-10 mg, 1-20 mg, 1-30 mg, 1-40 mg, 1-50 mg, 1-60 mg, 1-70 mg, 1-80 mg, 1-90 mg, 1-100 mg, 1-200 mg, 1-300 mg, 1-400 mg, 1-500 mg, 1-600 mg, 1-700 mg, 1-800 mg, 1-900 mg, 1-1000 mg, 1-11 mg, 1-12 mg, 1-13 mg, 1-13 mg, 1-14 mg, 1-15 mg, 1-16 mg, 1-17 mg, 1-18 mg, 1-19 mg, 10-20 mg, 10-30 mg, 10-40mg, 10-50 mg, 10-60 mg, 10-70 mg, 10-80 mg, 10-90 mg, 10-100 mg, 10-200 mg, 10-300mg, 10-400 mg, 10-500 mg, 10-600 mg, 10-700 mg, 10-800 mg, 10-900 mg, 10-1000 mg, 20-30 mg, 20-40 mg, 20-50 mg, 20-60 mg, 20-70 mg, 20-80 mg, 20-90 mg, 20-100 mg, 20-200mg, 20-300 mg, 20-400 mg, 20-500 mg, 20-600 mg, 20-700 mg, 20-800 mg, 20-900 mg, 20-1000 mg, 30-40 mg, 30-50 mg, 30-60 mg, 30-70 mg, 30-80 mg, 30-90 mg, 30-100 mg, 30-200 mg, 30-300 mg, 30-400 mg, 30-500 mg, 30-600 mg, 30-700 mg, 30-800 mg, 30-900 mg, 30-1000 mg, 40-50 mg, 40-60 mg, 40-70 mg, 40-80 mg, 40-90 mg, 40-100 mg, 40-200 mg, 40-300 mg, 40-400 mg, 40-500 mg, 40-600 mg, 40-700 mg, 40-800 mg、40-900 mg, 40-1000mg, 50-60mg, 50-70 mg, 50-80 mg, 50-90 mg, 50-100 mg, 50-200 mg, 50-300 mg, 50-400mg, 50-500 mg, 50-600 mg, 50-700 mg, 50-800 mg, 50-900 mg, 60-70 mg, 60-80 mg, 60-90mg, 60-100 mg, 60-200 mg, 60-300 mg, 60-400 mg, 60-500 mg, 60-600 mg, 60-700 mg, 60-800 mg, 60-900 mg, 60-1000 mg, 70-80 mg, 70-90 mg, 70-100 mg, 70-200 mg, 70-300 mg, 70-400 mg, 70-500 mg, 70-600 mg, 70-700 mg, 70-800 mg, 70-900 mg, 70-1000 mg, 80-90mg, 80-100 mg, 80-200 mg, 80-300 mg, 80-400 mg, 80-500 mg, 80-600 mg, 80-700 mg, 80-800 mg, 80-900 mg, 80-100 mg, 90-100 mg, 90-200 mg, 90-300 mg, 90-400 mg, 90-500 mg, 90-600 mg, 90-700 mg, 90-800 mg, 90-900 mg, 90-1000 mg, 100-150 mg, 100-200 mg, 100-300 mg, 100-400 mg, 100-500 mg, 100-600 mg, 100-700 mg, 100-800 mg, 100-900 mg or 100-1000 mg. In some embodiments, the oral compositions described herein are administered at a dose of about 0.01 mg, 0.02 mg, 0.03 mg, 0.05 mg, 0.07 mg, 0.1 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 8 mg, 8.5 mg, 9 mg, 9.5 mg, 10 mg, 10.5 mg, 11 mg, 11.5 mg, 12 mg, 12.5 mg, 13 mg, 13.5 mg, 14 mg, 14.5 mg, 15 mg, 15.5 mg, 16 mg, 16.5, 17.5 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mgmg, 17.5 mg, 18 mg, 18.5 mg, 19mg, 19.5 mg, 20 mg, 20.5 mg, 21 mg, 21.5 mg, 22 mg, 22.5 mg, 23 mg, 23.5 mg, 24 mg, 24.5mg, 25 mg, 25.5 mg, 26 mg, 26.5 mg, 27 mg, 27.5 mg, 28 mg, 28.5 mg, 29 mg, 29.5 mg, 30 mg, 30.5 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70mg, 80 mg, 90 mg or 95 mg . In some embodiments, the oral compositions described herein are administered at a dose of less than about 0.01 mg, 0.02 mg, 0.03 mg, 0.05 mg, 0.07 mg, 0.1 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 8 mg, 8.5 mg, 9 mg, 9.5 mg, 10 mg, 10.5 mg, 11 mg, 11.5 mg, 12 mg, 12.5 mg, 13 mg, 13.5 mg, 14 mg, 14.5 mg, 15 mg, 15.5 mg, 16 mg, 16.5 mg, 17 mg, 17.5 mg, 18 mg, 18.5 mg, 19 mg, 19.5 mg, 20 mg, 21.5 mg, 22.5 mg, 23.5 mg, 24.5 mg, 25.5 mg, 26.5 mg, 27.5 mg, 28.5 mg, 29.5 mg, 30.5 mg, .5 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg. In some embodiments, the oral compositions described herein are administered at a dose of greater than about 0.01 mg, 0.02 mg, 0.03 mg, 0.05 mg, 0.07 mg, 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 21.5 mg,0 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg, 3.5 mg, 4 mg, 4.5 mg, 5 mg, 5.5 mg, 6 mg, 6.5 mg, 7 mg, 7.5 mg, 8 mg, 8.5 mg, 9 mg, 9.5 mg, 10 mg, 10.5 mg, 11 mg, 11.5 mg, 12 mg, 12.5 mg, 13 mg, 13.5 mg, 14 mg, 14.5 mg, 15 mg, 15.5 mg, 16 mg, 16.5 mg, 17 mg, 17.5 mg, 18 mg, 18.5 mg, 19 mg, 19.5 mg, 20 mg, 20.5 mg, 21 mg, 21.5 mg, 22 mg, 22.5 mg, 23 mg, 23.5 mg, 24 mg, 24.5 mg, 25 mg, 25.5 mg, 26 mg, 26.5 mg, 27 mg, 27.5 mg, 28 mg, 28.5 mg, 29 mg, 29.5 mg, 30 mg, 30.5 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg or 100 mg.

[0189] In some embodiments, the dosage of the oral compositions described herein is about 0.1 mg-10 mg, 0.1 mg-25 mg, 0.1 mg-30 mg, 0.1 mg-50 mg, 0.1 mg-75 mg, 0.1 mg-100 mg, 0.5 mg-10 mg, 0.5 mg-25 mg, 0.5 mg-30 mg, 0.5 mg-50 mg, 0.5 mg-75 mg, 0.5 mg-100 mg, 1 mg-10 mg, 1 mg-25 mg, 1 mg-30 mg, 1 mg-50 mg, 1 mg-75 mg, 1 mg-100 mg, 2 mg-10 mg, 2 mg-25 mg, 2 mg-30 mg, 2 mg-50 mg, 2 mg-75 mg, 2 mg-100 mg, 3 mg-10 mg, 3 mg-25 mg, 3 mg-30 mg, 3 mg-50 mg, 3 mg-75 mg, 3 mg-100 mg, 4 mg-100 mg, 5 mg-10 mg, 5 mg-25 mg, 5 mg-30 mg, 5 mg-50 mg, 5 mg-75 mg, 5 mg-300 mg, 5 mg-200 mg, 7.5 mg-15 mg, 7.5 mg-25 mg, 7.5mg-30 mg, 7.5 mg-50 mg, 7.5 mg-75 mg, 7.5 mg-100 mg, 7.5 mg-200 mg, 10 mg-20 mg, 10 mg-25 mg, 10 mg -50 mg, 10 mg-75 mg, 10 mg-100 mg, 15 mg-30 mg, 15 mg-50 mg, 15 mg-100 mg, 20 mg-20 mg, 20 mg-100 mg, 30 mg-100 mg, 40 mg-100 mg, 10 mg-80 mg, 15 mg-80 In some embodiments, the oral compositions described herein are administered at doses of about 1 mg to 5 mg, 1 mg to 7.5 mg, 2.5 mg to 5 mg, 2.5 mg to 7.5 mg, 5 mg to 7.5 mg, 5 mg to 9 mg, 5 mg to 10 mg, 5 mg to 12 mg, 5 mg to 14 mg, 5 mg to 15 mg, 5 mg to 16 mg, 5 mg to 18 mg, 5 mg to 19 mg, 6 mg to 20 mg, 7 mg to 21 mg, 6 mg to 22 mg, 6 mg to 23 mg, 6 mg to 24 mg, 6 mg to 25 mg, 6 mg to 26 mg, 6 mg to 27 mg, 6 mg to 28 mg, 7 mg to 29 mg, 8 mg to 30 mg, 9 mg to 10 mg, 10 mg to 11 mg, 11 mg to 12 mg, 12 mg to 13 mg, 13 mg to 14 mg, 15 mg to 16 mg, 15 mg to 17 mg, 16 mg to 18 mg, 17 mg to 29 mg, 6 mg to 25 mg, 6 mg to 26 mg, 6 mg to 27 mg, 6 mg to 28 mg, 6 mg to 29 mg,mg-20mg、5 mg-22 mg、5 mg-24 mg、5 mg-26 mg、5 mg-28 mg、5 mg-30 mg、5 mg-32 mg、5 mg-34mg、5 mg-36 mg、5 mg-38 mg、5 mg-40 mg、5 mg-42 mg、5 mg-44 mg、5 mg-46 mg、5 mg-48mg、5 mg-50 mg、5 mg-52 mg、5 mg-54 mg、5 mg-56 mg、5 mg-58 mg、5 mg-60 mg、7 mg-7.7mg、7 mg-9 mg、7 mg-10 mg、7 mg-12 mg、7 mg-14 mg、7 mg-15 mg、7 mg-16 mg、7 mg-18mg、7 mg-20 mg、7 mg-22 mg、7 mg-24 mg、7 mg-26 mg、7 mg-28 mg、7 mg-30 mg、7 mg-32mg、7 mg-34 mg、7 mg-36 mg、7 mg-38 mg、7 mg-40 mg、7 mg-42 mg、7 mg-44 mg、7 mg-46mg、7 mg-48 mg、7 mg-50 mg、7 mg-52 mg、7 mg-54 mg、7 mg-56 mg、7 mg-58 mg、7 mg-60mg、9 mg-10 mg、9 mg-12 mg、9 mg-14 mg、9 mg-15 mg、9 mg-16 mg、9 mg-18 mg、9 mg-20mg、9 mg-22 mg、9 mg-24 mg、9 mg-26 mg、9 mg-28 mg、9 mg-30 mg、9 mg-32 mg、9 mg-34mg、9 mg-36 mg、9 mg-38 mg、9 mg-40 mg、9 mg-42 mg、9 mg-44 mg、9 mg-46 mg、9 mg-48mg、9 mg-50 mg、9 mg-52 mg、9 mg-54 mg、9 mg-56 mg、9 mg-58 mg、9 mg-60 mg、10 mg-12mg、10 mg-14 mg、10 mg-15 mg、10 mg-16 mg、10 mg-18 mg、10 mg-20 mg、10 mg-22 mg、10mg-24 mg、10 mg-26 mg、10 mg-28 mg、10 mg-30 mg、10 mg-32 mg、10 mg-34 mg、10mg-36mg、10 mg-38 mg、10 mg-40 mg、10 mg-42 mg、10 mg-44 mg、10 mg-46 mg、10 mg-48 mg、10mg-50 mg、10 mg-52 mg、10 mg-54 mg、10 mg-56 mg、10 mg-58 mg、10 mg-60 mg、12 mg-14mg、12 mg-15 mg、12 mg-16 mg、12 mg-18 mg、12 mg-20 mg、12 mg-22 mg、12 mg-24 mg、12mg-26 mg、12 mg-28 mg、12 mg-30 mg、12 mg-32 mg、12 mg-34 mg、12 mg-36 mg、12 mg-38mg、12 mg-40 mg、12 mg-42 mg、12 mg-44 mg、12 mg-46 mg、12 mg-48 mg、12 mg-50 mg、12mg-52 mg、12 mg-54 mg、12 mg-56 mg、12 mg-58 mg、12 mg-60 mg、15 mg-16 mg、15 mg-18mg、15 mg-20 mg、15 mg-22 mg、15 mg-24 mg、15 mg-26 mg、15 mg-28 mg、15 mg-30 mg、15mg-32 mg、15 mg-34 mg、15 mg-36 mg、15 mg-38 mg、15 mg-40 mg、15 mg-42 mg、15 mg-44mg、15 mg-46 mg、15 mg-48 mg、15 mg-50 mg、15 mg-52 mg、15 mg-54 mg、15 mg-56 mg、15mg-58 mg、15 mg-60 mg、17 mg-18 mg、17 mg-20 mg、17 mg-22 mg、17 mg-24 mg、17 mg-26mg、17 mg-28 mg、17 mg-30 mg、17 mg-32 mg、17 mg-34 mg、17 mg-36 mg、17 mg-38 mg、17mg-40 mg、17 mg-42 mg、17 mg-44 mg、17 mg-46 mg、17 mg-48 mg、17 mg-50 mg、17 mg-52mg、17 mg-54 mg、17 mg-56 mg、17 mg-58 mg、17 mg-60 mg、20 mg-22 mg、20 mg-24mg、20mg-26 mg、20 mg-28 mg、20 mg-30 mg、20 mg-32 mg、20 mg-34 mg、20 mg-36 mg、20 mg-38mg、20 mg-40 mg、20 mg-42 mg、20 mg-44 mg、20 mg-46 mg、20 mg-48 mg、20 mg-50 mg、20mg-52 mg、20 mg-54 mg、20 mg-56 mg、20 mg-58 mg、20 mg-60 mg、22 mg-24 mg、22 mg-26mg、22 mg-28 mg、22 mg-30 mg、22 mg-32 mg、22 mg-34 mg、22 mg-36 mg、22 mg-38 mg、22mg-40 mg、22 mg-42 mg、22 mg-44 mg、22 mg-46 mg、22 mg-48 mg、22 mg-50 mg、22 mg-52mg、22 mg-54 mg、22 mg-56 mg、22 mg-58 mg、22 mg-60 mg、25 mg-26 mg、25 mg-28 mg、25mg-30 mg、25 mg-32 mg、25 mg-34 mg、25 mg-36 mg、25 mg-38 mg、25 mg-40 mg、25 mg-42mg、25 mg-44 mg、25 mg-46 mg、25 mg-48 mg、25 mg-50 mg、25 mg-52 mg、25 mg-54 mg、25mg-56 mg、25 mg-58 mg、25 mg-60 mg、27 mg-28 mg、27 mg-30 mg、27 mg-32 mg、27 mg-34mg、27 mg-36 mg、27 mg-38 mg、27 mg-40 mg、27 mg-42 mg、27 mg-44 mg、27 mg-46 mg、27mg-48 mg、27 mg-50 mg、27 mg-52 mg、27 mg-54 mg、27 mg-56 mg、27 mg-58 mg、27 mg-60mg、30 mg-32 mg、30 mg-34 mg、30 mg-36 mg、30 mg-38 mg、30 mg-40 mg、30 mg-42 mg、30mg-44 mg、30 mg-46 mg、30 mg-48 mg、30 mg-50 mg、30 mg-52 mg、30 mg-54 mg、30mg-56mg, 30 mg-58 mg, 30 mg-60 mg, 33 mg-34 mg, 33 mg-36 mg, 33 mg-38 mg, 33 mg-40 mg, 33mg-42 mg, 33 mg-44 mg, 33 mg-46 mg, 33 mg-48 mg, 33 mg-50 mg, 33 mg-52 mg, 33 mg-54mg, 33 mg-56 mg, 33 mg-58 mg, 33 mg-60 mg, 36 mg-38 mg, 36 mg-40 mg, 36 mg-42 mg, 36mg-44 mg, 36 mg-46 mg, 36 mg-48 mg, 36 mg-50 mg, 36 mg-52 mg, 36 mg-54 mg, 36 mg-56mg, 36 mg-58 mg, 36 mg-60 mg, 40 mg-42 mg, 40 mg-44 mg, 40 mg-46 mg, 40 mg-48 mg, 40mg-50 mg, 40 mg-52 mg, 40 mg-54 mg, 40 mg-56 mg, 40 mg-58 mg, 40 mg-60 mg, 43 mg-46mg, 43 mg-48 mg, 43 mg-50 mg, 43 mg-52 mg, 43 mg-54 mg, 43 mg-56 mg, 43 mg-58 mg, 42mg-60 mg, 45 mg-48 mg, 45 mg-50 mg, 45 mg-52 mg, 45 mg-54 mg, 45 mg-56 mg, 45 mg-58mg, 45 mg-60 mg, 48 mg-50 mg, 48 mg-52 mg, 48 mg-54 mg, 48 mg-56 mg, 48 mg-58 mg, 48mg-60 mg, 50 mg-52 mg, 50 In some embodiments, the dose of the oral compositions described herein is greater than, equal to, or 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 25In some embodiments, the present invention relates to an oral dosage of 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. In some embodiments, the dosage 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.

[0190] To prepare a solid composition such as a tablet or capsule, the compound or extract is mixed with a carrier (e.g., conventional tableting ingredients such as corn starch, lactose, sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicalcium phosphate or gum) 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 the disclosed compound. Tablets or pills containing the compound or extract can be coated or otherwise compounded to provide a dosage form with the advantage of a long-lasting effect.

[0191] The liquid form of the compound of the present invention or extract incorporated for oral or parenteral administration includes aqueous solution, appropriately flavored syrup, aqueous or oily suspension and flavored emulsion containing edible oil and elixir and similar vehicles. Suitable dispersants or suspending agents for aqueous suspensions include synthetic natural gums, such as tragacanth, gum arabic, alginate, dextran, sodium carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone or gelatin. Liquid preparations for oral administration can be in the form of, for example, solutions, syrups or suspensions, or they can be in the form of dry products redissolved with water or other suitable vehicles before use. These liquid preparations can be prepared by conventional methods using acceptable additives, such as suspending agents (such as sorbitol syrup, methylcellulose or hydrogenated edible fats); emulsifiers (such as lecithin or gum arabic); non-aqueous vehicles (such as almond oil, oily esters or ethanol); preservatives (such as methylparaben or propylparaben, or sorbic acid); and artificial or natural pigments and / or sweeteners.

[0192] The method for preparing the formulation or composition of the present invention comprises the step of combining the compound or extract of the present invention with a carrier and optionally one or more auxiliary ingredients and / or active ingredients. Generally speaking, the formulation is prepared by uniformly and closely combining the compound or extract of the present invention with a liquid carrier or a finely powdered solid carrier or both, and then shaping the product as needed. Thus, the disclosed formulation can consist of or consist essentially of a combination of the compound or extract described herein and a suitable carrier.

[0193] When the compounds of the present disclosure or extracts are administered to humans and animals as medicines, nutraceuticals, or dietary supplements, they can be administered alone or in the form of a composition containing, for example, 0.1% to 99% active ingredient and an acceptable carrier. In some embodiments, one or more compounds of the present disclosure or extracts 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%, 99% w / w, or a range including and / or spanning the aforementioned values.

[0194] In some embodiments, fortified food, food supplement or medical food can also include one or more of protein, carbohydrate and / or fat, which are used for health (preferably human body), to maintain growth, repair and life process and provide energy. When composition is provided as fortified food, food supplement or medical food, composition includes selected compound of the present disclosure, composition or extract, so that they can be eaten with food simultaneously or approximately simultaneously. In some embodiments, fortified food, food supplement or medical food is usually eaten before food is eaten or after food is eaten within about one hour. In some embodiments, fortified food, food supplement or medical food is usually eaten before food is eaten or after food is eaten within about fifteen minutes. In some embodiments, fortified food, food supplement or medical food is usually eaten before food is eaten or after food is eaten within about five minutes. In some embodiments, dietary supplement or nutritional supplement can also be eaten simultaneously with food, even with fortified food, food supplement or medical food.

[0195] Methods and uses

[0196] In aspects, the present disclosure provides methods and uses for improving, restoring, regulating or maintaining sleep. According to this method, an effective amount of one or more compounds or compositions of the present disclosure is provided to a subject in need thereof so that the subject's sleep is improved, restored, regulated or maintained. As used herein, the term "subject" refers to an animal, preferably a mammal. In some embodiments, the subject is a veterinarian, companion animal, farm animal, laboratory animal or zoological animal. In other embodiments, the subject is a human.

[0197] Several signaling molecules have been found to play a role in sleep. Various neurotransmitters (including norepinephrine, acetylcholine, histamine, dopamine, serotonin, and the neuropeptides orexin A and orexin B (also known as hypocretin)) can promote wakefulness. Orexin is a neuropeptide involved in regulating the sleep-wake cycle, feeding patterns, energy balance, and stress in mammals. Disorders or loss of orexin signaling are 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 act as antagonists of both orexin receptor 1 and orexin receptor 2. In some embodiments, the compounds or compositions described herein can be used in methods for antagonizing orexin receptor activity in subjects requiring such inhibition, the methods comprising administering an effective amount of the compound. The utility of compounds according to the present disclosure as OX1 and / or OX2 antagonists can be readily determined without undue experimentation by methods known in the art, including the "FLIPR Ca 2+ Flux determination" (Okumura et al., Biochem. Biophys. Res. Comm. 280:976-981, 2001).

[0198] Calcium influx can be important for generating on / off state oscillations and REM sleep. In some embodiments, the plant extracts or compounds described herein provide 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.

[0199] Sleep deprivation can lead to ER stress and endoplasmic reticulum kinase (pERK) pathway activation. In some embodiments, the plant extracts or compounds described herein provide a reduction in pERK 1 / 2 phosphorylation. In some embodiments, a method for inactivating pERK 1 / 2 phosphorylation in a subject comprises administering a composition as provided herein.

[0200] In some embodiments, the method comprises rapidly inducing sleep in a subject by administering a composition as described herein. In some embodiments, the subject falls asleep faster 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 values ​​included and / or ranges across the foregoing values.

[0201] In some embodiments, the method comprises promoting quality sleep in a subject by administering a composition as 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 values ​​included and / or ranges across the foregoing values.

[0202] In some embodiments, the method comprises providing effective sleep to a subject by administering a composition as described herein. In some embodiments, the effective sleep of the subject 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 values ​​included and / or ranges across the foregoing values.

[0203] In some embodiments, the method includes providing a complete night's sleep to the subject by administering a composition as described herein. In some embodiments, the average sleep time of the subject is extended by an additional approximately 15 minutes, 30 minutes, 45 minutes, 60 minutes, 75 minutes, 90 minutes, 105 minutes, 120 minutes, 135 minutes, 150 minutes, 165 minutes, 180 minutes, or the aforementioned values ​​and / or the range across the aforementioned values. In some embodiments, the method includes reducing the time it takes for the subject to fall asleep by administering a composition as described herein. In some embodiments, the average time it takes for the subject to fall asleep is reduced by approximately 15 minutes, 30 minutes, 45 minutes, 60 minutes, 75 minutes, 90 minutes, 105 minutes, 120 minutes, 135 minutes, 150 minutes, 165 minutes, 180 minutes, or the aforementioned values ​​and / or the range across the aforementioned values.

[0204] In some embodiments, the method comprises increasing a subject's slow-wave sleep stages 1 to 4 by administering a composition described herein. In some embodiments, the method comprises increasing a subject's REM sleep by administering a composition described herein. In some embodiments, the method comprises increasing a subject's deep sleep by administering a composition described herein. Humans experience several different sleep stages. These include slow-wave sleep stage 1 (SWS1), slow-wave sleep stage 2 (SWS2), slow-wave sleep stage 3 (SWS3), slow-wave sleep stage 4 (SWS4), and rapid eye movement (REM). SWS1 and SWS2 are both light sleep stages, during which a person is relatively easy to awaken. Light sleep is typically more common in the second half of sleep. SWS3 and SWS4 are both deep sleep stages, during which a sleeper is difficult to awaken. Deep sleep is more common in the first half of sleep, with each sleep stage subsequently becoming shorter in duration. REM is the sleep stage during which a person experiences the most vivid dreams. The waveform patterns are similar to those observed when a person is awake. In healthy individuals, SWS1 accounts for approximately 5% of sleep, SWS2 accounts for approximately 50% of sleep, SWS3 accounts for approximately 10% of sleep, SWS4 accounts for approximately 10% of sleep, and REM accounts for approximately 25% of sleep. In some embodiments, the method can increase slow-wave sleep stage 1 by approximately 1% to approximately 5% of a subject's sleep. In some embodiments, the method can increase slow-wave sleep stage 2 by approximately 10% to approximately 50% of a subject's sleep. In some embodiments, the method can increase slow-wave sleep stage 3 by approximately 2% to approximately 10% of a subject's sleep. In some embodiments, the method can increase slow-wave sleep stage 4 by approximately 2% to approximately 10% of a subject's sleep. In some embodiments, the method can increase REM sleep by approximately 10% to approximately 25% of a subject's sleep.

[0205] In some embodiments, the method improves a sleep disorder in a subject by administering a composition described herein to the subject. Sleep disorders are described in the International Classification of Sleep Disorders (ICDS). The ICDS-3, published in 2014, characterizes sleep disorders as one of the following categories: (1) insomnia; (2) sleep-related breathing disorders; (3) central hypersomnias; (3) circadian rhythm sleep-wake disorders; (4) parasomnias; (5) sleep-related movement disorders. Therefore, the sleep disorder treated by the oral composition described herein can include any sleep disorder in the following categories: (1) insomnia; (2) sleep-related breathing disorders; (3) central hypersomnias; (3) circadian rhythm sleep-wake disorders; (4) parasomnias; (5) sleep-related movement disorders. Specifically, the oral composition can effectively treat sleep disorders selected from the following: insomnia, narcolepsy, hypersomnia, sleep apnea, periodic limb movement disorder, restless legs syndrome, night eating (drinking) syndrome, jet lag, shift work sleep disorder, irregular sleep-wake pattern, 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 any other sleep disorder.

[0206] By "effective amount" is meant the amount of a provided drug that, when administered to a patient, is sufficient to achieve an effect. In the context of a therapeutic method, this effect may be treating a sleep disorder. Thus, an "effective amount" may be a "therapeutically effective amount." By "therapeutically effective amount" is meant the amount of a provided drug that, when administered to a subject, is sufficient to treat a disease or a symptom of a disease.

[0207] As used herein, the terms "treating," "treatment," "treat," and the like mean affecting a subject, tissue, or cell to obtain a desired pharmacological and / or physiological effect. The effect may be preventative, i.e., completely or partially preventing a disease or associated symptoms, or reducing the severity of a disease or associated symptoms, and / or the effect may be therapeutic, i.e., partially or completely curing a disease. For example, therefore, reference to "treating" a sleep disorder may encompass: (a) helping a subject fall asleep; (b) helping a subject stay asleep once asleep; (c) alleviating or ameliorating the effects of a sleep disorder, e.g., increasing wakefulness during non-sleep periods; or (d) preventing a sleep disorder in a subject susceptible to or at risk of a sleep disorder so that the subject does not develop or develop a sleep disorder, or so that the sleep disorder develops in a less severe form.

[0208] In some embodiments, a method of treating insomnia in a subject comprises administering one or more compounds described herein. In some embodiments, a method of treating insomnia in a subject comprises administering an oral composition described herein. The symptoms and severity of insomnia can be measured using the Insomnia Severity Index (ISI) questionnaire. Typically, the ISI is administered by a clinician, nurse, or researcher, or can be self-administered by the patient. The ISI assesses both nighttime and daytime components of insomnia and is available in multiple languages. The ISI asks seven questions, each scored on a scale of 0 to 4, relating to (1) difficulty falling asleep, (2) difficulty staying asleep, (3) problems waking up too early, (4) satisfaction with current sleep patterns, (5) perception of the degree to which the sleep problem causes concern to others, (6) degree of concern about the sleep problem, and (7) degree to which the sleep problem interferes with daily life. The method can provide improvements in one or more of these seven aspects of insomnia. In some embodiments of the method of treatment, the subject to be treated can have an initial ISI score of 7 or higher, and in some cases, the initial ISI score can be 10 or higher. In some embodiments, the method of treating insomnia can provide a reduction in the patient's ISI score relative to an initial ISI score. This reduction in ISI score can be a reduction of 1, 2, 3, 4, 5, 6, or more units on the ISI scale, and preferably results in the patient having an ISI score of 7 or less after treatment.

[0209] The ISI can be used alone to assess the severity of insomnia in a subject, or can be used in conjunction with one or more other questionnaires, such as the Quality of Life Happiness and Satisfaction Questionnaire (Q-les-Q), the Work and Social Adjustment Scale (WSAS), the Depression Anxiety Stress Scale (DASS), the Dysfunction Beliefs About Sleep (DBAS), the Multidimensional Fatigue Self-Rating Scale, and any other recognized questionnaires known in the art.

[0210] Patients are typically assessed using one or more questionnaires before starting treatment and then at regular intervals during treatment (e.g., 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, or 8 weeks). During-treatment assessments can begin 2 weeks after treatment begins.

[0211] In some embodiments, treatment can be continued for up to 14 days, for example, treatment can be continued for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, or 14 days. In some embodiments, treatment is continued for more than 14 days, for example, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 12 months, 18 months, 24 months, 36 months, or longer.

[0212] Typically, the oral composition is administered once daily, preferably shortly before the patient attempts to fall asleep. In some embodiments, the oral composition is administered within about 2 hours of the patient attempting to fall asleep, for example, within about 1.5 hours, about 1 hour, or about 30 minutes before bedtime.

[0213] In some embodiments, insomnia can be assessed by measuring one or more objective indicators of sleep. Objective indicators of sleep can be measured by polysomnography (PSG) and / or actigraphy. Objective indicators of sleep can include measurements of: sleep onset latency (SO); wake time after sleep onset (WASO); total sleep time (TST); sleep efficiency (SE); REM and NREM sleep patterns, including slow-wave sleep patterns and the percentage of time in all sleep stages; sleep apnea; periodic limb movements; and combinations thereof. In some embodiments, the method for treating insomnia can provide one or more objective indicators of sleep, for example, improvements in 2, 3, 4, 5, 6 or more objective indicators of sleep.

[0214] In some embodiments, compound of the present disclosure or composition can be used in combination with other compounds to improve sleep quality. In some embodiments, compound of the present disclosure or composition can be used in combination with other compounds to treat or prevent sleep disorders and sleep disorders. In some embodiments, other compounds can include, but are not limited to: sedatives, sleeping pills, anxiolytics, antipsychotics, anxiolytics, antihistamines, benzodiazepines, barbiturates, cyclopyrrolidone drugs, GABA agonists, 5HT-2 antagonists (including 5HT-2A antagonists and 5HT-2A / 2C antagonists), histamine antagonists (including histamine H3 antagonists), histamine H3 inverse agonists, imidazopyridines, weak tranquilizers, melatonin agonists and antagonists, melatonergic agents, prokinetic protein agonists and antagonists, pyrazolopyrimidines, T-type calcium channel antagonists, triazolopyridines, etc., such as: adizalam adinazolam, allobarbital, alonimid, alprazolam, amitriptyline, amobarbital, amoxapine, armodafinil, APD-125, bentazepam, benzoctamine, brotizolam, bupropion, buspirone one), butabarbital, butalbital, capromorelin, capuride, carbocloral, chloral betaine, chloral hydrate, chlordiazepoxide, clomipramine, clonazepam, cloperidone, clorazepate, clorethate, clozapine , clonazepam, cyprazepam, desipramine, dexclamol, diazepam, dichloralphenazone, divalproex, diphenhydramine, doxepin, EMD-281014, eplivanserin, estazolam, eszopiclone,Ethchlorynol, etomidate, fenobam, flunitrazepam, flurazepam, fluvoxamine, fluoxetine, fosazepam, gaboxadol, glutethimide, halazepam, hydroxyzine, ibutamoren, imipramine, indiplon, lithium, lorazepam am), lormetazepam, LY-156735, maprotiline, MDL-100907, mecloqualone, melatonin, mephobarbital, meprobamate, methaqualone, methyprylon, midaflur, midazolam, modafinil, nefazodone, NGD-2-73, nisobamate, Nitrazepam, nortriptyline, ornortriptyline, oxazepam, paroxetine, pentobarbital, perlapine, perphenazine, phenelzine, phenobarbital, prazepam, promethazine, propofol, protriptyline e), quazepam, ramelteon, reclazepam, roletamide, secobarbital, sertraline, suproclone, TAK-375, temazepam, thioridazine, tiagabine, tracazolate, tranylcypromaine, trazodone, triazolam,Trepipam, tricetamide, triclofos, trifluoperazine, trimetozine, trimipramine, uldazepam, venlafaxine, zaleplon, zolazepam, zopiclone, zolpidem and salts thereof, and combinations thereof, etc., or the compounds of the present invention can be administered in combination with physical methods such as light therapy or electrical stimulation.

[0215] The present disclosure also provides methods and uses for treating, improving, restoring, regulating or maintaining a subject's weight. According to this method, an effective amount of one or more compounds or compositions of the present disclosure is provided to a subject in need thereof so that the subject's weight is treated, improved, restored, regulated or maintained. In some embodiments, the one or more compounds, plant extracts or compositions are present in an amount sufficient to promote health and well-being.

[0216] In some embodiments, the method for weight management of a subject includes administering one or more compounds described herein or compositions to the subject. In some embodiments, the subject reduces and / or maintains body mass. In some embodiments, compared with the original body mass of the subject, body mass reduces and / or maintains 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 includes the aforementioned values ​​and / or the scope across the aforementioned values.

[0217] In some embodiments, the method for suppressing appetite comprises administering a composition as described herein to a subject. In some embodiments, after administering one or more compounds or compositions as described herein, the subject's sense of fullness 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 including the aforementioned values ​​and / or the range across the aforementioned values.

[0218] In some embodiments, the method for controlling a subject's appetite comprises administering a composition as described herein to the subject. In some embodiments, after administering one or more compounds or compositions as described herein, the subject's appetite decreases 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 including the aforementioned values ​​and / or the range across the aforementioned values.

[0219] In some embodiments, the method for inducing the satiety of a subject includes applying compositions described herein to a subject. In some embodiments, after applying one or more compounds described herein or compositions, the subject's induced satiety 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 includes the aforementioned values ​​and / or the scope across the aforementioned values. Satiety and / or satiety can be evaluated by consumer surveys (for example, for the mankind), and the survey can show the statistically significant index of satiety and / or satiety increase.

[0220] Also provided is a method for promoting weight loss by applying the compositions provided herein to a subject. In some embodiments, after administering one or more compounds described herein or compositions, the subject's body mass reduces 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 includes the aforementioned values ​​and / or the scope across the aforementioned values. The amount and duration of this administration will depend on individual weight loss demand and health status, and can be evaluated by one of ordinary skill in the art. The weight loss of the subject over time can be measured to determine whether weight loss is occurring. Weight loss can be compared with a control animal that is not administered with an ingestible composition.

[0221] Example

[0222] The following non-limiting examples are provided to further illustrate the present disclosure.

[0223] Example 1

[0224] A Dionex™ Accelerated Solvent Extractor 350 was used to extract the plant material. Four 100 mL stainless steel ASE extraction tanks were filled with 25 g of ground plant tissue. Static extraction was performed at a preset temperature of 60°C for a total of twelve 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 chromatography column. Elution was performed using a mobile phase consisting of water + 0.1% formic acid (A) and CH3CN + 0.1% formic acid (B), followed by a gradient elution from 1% to 3% B over 3 minutes, then increasing to 100% B over 22 minutes, and then maintaining 100% B at a flow rate of 30 mL / min for 7 minutes. High-activity 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.

[0225] Example 2

[0226] This example is a prophetic example. In this example, the extraction method of Example 1 was applied to plant tissues from Table 1.

[0227] Table 1

[0228] The amount of costunolide or other compounds of interest such as was determined in certain extracts (percent of extract, w / w). The compounds were quantified by normalizing the results to the weight of the extract. The results of these analyses were confirmed.

[0229] Example 3

[0230] The oral composition is provided before going to bed every day in the hope of obtaining a good night's sleep. The oral composition adopts a small capsule preparation and comprises an extract of Eupatorium perforatum and a carrier.

[0231] Directions for use: For oral compositions, take one capsule orally once daily before bedtime with an 8-ounce glass of water. Preferably, take the oral composition in anticipation of a full night's sleep.

[0232] Example 4

[0233] In this example, the in vitro biological activities of the naturally occurring compounds in the plants described herein were tested to determine whether they could modulate orexin receptors. Structures 20 to 38 were identified as modulating orexin receptors (Orx1, Orx2), or both. Figures 1 to 11Compounds 20 to 30 are shown to modulate Orx2 agonism. Figure 12 Compounds 31 to 38 were shown to modulate orexin receptor (Orx1, Orx2) agonism.

[0234] Example 5

[0235] In this example, the in vitro biological activities of naturally occurring compounds were evaluated.

[0236] For this example, the following protocol was used: 1.) cells were plated in 20 μL of cell plating reagent; 2.) cells were incubated overnight at 37°C and 5% CO2; 3.) cells were treated with 2.5 μL of 10X antagonist prepared in compound dilution buffer (for OR2 screening, 2.5 μL of 1:100 natural product sample was prepared in DiscoverX cell plating reagent. A control antagonist, Seltorexant, 10X stock solution was prepared at 1500 nM); 4.) incubated for 30 minutes at 37°C and 5% CO2; 5.) cells were treated with 2.5 μL of 10X agonist prepared in compound dilution buffer (for OR2 screening, 2.5 μL of 10X orexin B EC80, 252.7 nM); 6.) incubated for 90 minutes at 37°C and 5% CO2; 7.) 12.5 μL of working detection solution; 8.) incubate at room temperature in the dark for 1 hour; and 9.) read the chemiluminescent signal.

[0237] The plants described herein were tested to determine the concentration (in μM) required to achieve a relative IC50 for the OR2 receptor, the absolute agonism percentage achieved at the μM concentration of the relative OR2 IC50, the percent receptor activity at the concentration (in μM) required to achieve an IC50 in OR2, the percent cell viability at the μM concentration of IC50 as measured by the XTT assay, the concentration of the fraction (in multiple dilutions) required to achieve an IC50 for OR2, and the percent receptor activity at the concentration of the fraction (in multiple dilutions) required to achieve an IC50 for OR2. The results are described in Table 2.

[0238] Table 2

[0239] Example 6

[0240] In this example, the in vivo tolerance of Compound 26, Compound 21, Compound 29, and Compound 13 was evaluated.

[0241] Upon arrival at the testing facility, naive rats (male Sprague-Dawley rats) were housed in cages for up to 7 days to acclimate to the operant chamber environment, with free access to food and water. On the day of the experiment, at least one hour before the start of any experiment, animals were acclimated to the laboratory environment. All animals were tail-tagged, weighed, and randomly assigned to treatment groups. Animals (n=3 per dose) were treated with Compound 26, Compound 21, Compound 29, and Compound 13 (10 mL / kg, orally). For each compound, a dose-escalation protocol was used, starting at 30 mg / kg and tested for up to four doses. 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 protocol, if the 100 mg / kg dose was well tolerated, the dose was increased to 315 mg / kg. If not tolerated, the dose was reduced to 60 mg / kg. These patterns continued to the next decision point: if 315 mg / kg was well tolerated, the dose was increased to a maximum of 500 mg / kg. If 315 mg / kg was not tolerated, the dose was reduced to 200 mg / kg. Following compound administration, each animal was placed in a clear Perspex cage and observed for 60 minutes, with recordings taken at 15, 30, and 60 minute time points.

[0242] Compound 26 was provided by Arctom as a yellow powder. For the 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. Therefore, the dose volume per animal was approximately 3 mL. There were 3 animals per group, and the total dose volume required for each 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 thorough mixing and dissolution, the solution was sonicated to obtain a yellow milky solution. Similar procedures were used for other doses.

[0243] Compound 21 was provided by Brightseed, Inc. as a yellow powder. A vehicle of 10% dimethyl sulfoxide (DMSO) in 20% hydroxypropyl beta-cyclodextrin (HPBC) was used for formulation. Four dose concentrations were prepared: for the 30 mg / kg dose, 45 mg of arginine was weighed and dissolved in a total volume of 15 mL (1.5 mL DMSO + 13.5 mL 20% HPBC). To ensure thorough mixing and dissolution, the solution was sonicated to produce a yellow, milky solution. Similar procedures were used for the other doses.

[0244] Compound 29 was provided by Brightseed, Inc. as an orange powder. 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 thorough mixing and dissolution, the solution was sonicated, adding 10 μL of NaOH each time, and then sonicated again until no solid matter remained, resulting in a thick, dark red solution. A similar procedure was used for all doses.

[0245] Compound 13 was provided by Ambeed, Inc. as a yellow powder. 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 thorough mixing and dissolution, the solution was sonicated, with 10 μL of NaOH added each time, followed by further sonication until no solid material remained, resulting in a bright yellow solution. A similar procedure was used for all doses.

[0246] If three or more adverse reactions (or any serious adverse reactions) occur at a particular dose over a full 60-minute period, the compound is considered to be intolerable. After administration of the compound, the animals are observed for adverse reactions such as pronounced piloerection, abnormal breathing, arched back, vocalization, decreased activity, etc. When the animal shows decreased activity and does not sleep in the cage and stops moving, it is determined to be decreased activity. Mild - slightly decreased activity, with a reaction when stimulated. Moderate - decreased activity, with a weaker reaction when stimulated. Pica means that the animal is eating non-food items, such as bedding. The results of Example 5 are summarized in Table 3 below.

[0247] Table 3. Adverse reaction profiles of different compounds at different time points.

[0248]

[0249] In summary, all animals receiving all four doses (30 mg / kg, 100 mg / kg, 315 mg / kg, and 500 mg / kg) of Compound 26, Compound 21, Compound 29, and Compound 13 can be considered well tolerated. For the use of substantially any plural and / or singular term herein, one skilled in the art can convert the term from plural to singular and / or from singular to plural depending on the context and / or application. For clarity, various singular / plural permutations may be explicitly listed herein.

[0250] It will be understood by those skilled in the art that, in general, the terms used herein, and particularly in the appended claims (e.g., the bodies of the appended claims), are generally intended to be "open" terms (e.g., the term "including" should be interpreted as "including but not limited to," the term "having" should be interpreted as "having at least," the term "includes" should be interpreted as "including but not limited to," etc.). It will also be understood by those skilled in the art that if a specific number of claim recitations is intended, that intent will be expressly recited in the claim, and if that recitation is absent, that intent is not present. For example, to aid understanding, the following appended claims may contain the use of the introductory phrases "at least one" and "one or more" to introduce claim recitations. However, the use of such phrases should not be interpreted as meaning that introducing a claim recitation with the indefinite article "a" or "an" limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even if the same claim includes 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 applies to the use of definite articles to introduce claim recitations. Furthermore, even if a specific number of introduced claim recitations is expressly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (e.g., the mere recitation "two recitations" without other modifiers means at least two recitations, or two or more recitations). Furthermore, where a convention similar to "at least one of A, B, and C, etc." is used, such construction is generally intended to be taken in the sense of the convention as understood by those skilled in the art (e.g., "a system having at least one of A, B, and C" includes but is not limited to systems having only A, only B, only C, both A and B, both A and C, both B and C, and / or both A, B, and C, etc.).

[0251] In the case of the convention of "at least one of A, B, or C", such construction is generally intended to be carried out in the conventional meaning understood by those skilled in the art (for example, "a system having at least one of A, B, or C" includes but is not limited to systems having only A, only B, only C, both A and B, both A and C, both B and C, and / or both A, B, and C, etc.). Those skilled in the art will also understand that, in fact, any transitional words and / or phrases indicating two or more alternative terms, whether in the specification, claims, or drawings, should be understood to include the possibility of including one, either, or both terms. For example, the phrase "A or B" will be understood to include the possibility of "A" or "B" or "A and B".

[0252] In addition, where features or aspects of the disclosure are described in terms of Markush groups, 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.

[0253] Those skilled in the art will understand that, for any and all purposes, such as providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be readily understood to fully describe and enable the same range to be broken down into at least equal halves, thirds, quarters, fifths, tenths, and so forth. As a non-limiting example, each range discussed herein can readily be broken down into a lower third, a middle third, and an upper third, and so forth. Those skilled in the art will also understand that all language such as "up to," "at least," "greater than," "less than," and so forth, includes the listed quantity and refers to a range that can subsequently be broken down into subranges as discussed above. Finally, those skilled in the art will understand that a range includes each individual member. Thus, for example, a group having 1 to 3 items refers to groups having 1, 2, or 3 items. Similarly, a group having 1 to 5 items refers to groups having 1, 2, 3, 4, or 5 items, and so forth. While various aspects and embodiments have been disclosed herein, those skilled in the art will appreciate other aspects and embodiments. The various aspects and embodiments disclosed herein are for purposes of illustration only and are not intended to be limiting, with the true scope and spirit being indicated by the following claims.

Claims

1. An oral composition for improving, restoring, regulating or maintaining sleep, comprising: A compound of formula (I); (I) where R 1 is selected from 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; R 2 is selected from 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; R 3 is selected from 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; R 4 is selected from 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; R 5 is selected from 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; R 6 is selected from 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; R 7 is selected from 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; L is –Z 1 -Z 2 or –Z 1 -Z 2 -Z 3 ; Z1 is -CH2-, -O-, -NH-, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted C6 to C 10 aryl, optionally substituted -C3-C8 heterocyclic group or optionally substituted C3 to C 10 Heteroaryl, in some embodiments, Z1 is optionally substituted -C3-C8 heterocyclyl; 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 heterocyclic group or optionally substituted -C3-C 10 heteroaryl; Z 3 is hydrogen, deuterium, halo, –CH2–, –O–, optionally substituted –C3-C8 cycloalkyl, optionally substituted –C6-C 10 aryl, optionally substituted -C3-C8 heterocyclic group or optionally substituted -C3-C 10 heteroaryl; and One or more carriers or excipients.

2. The oral composition of claim 1, wherein the compound is represented by formula (IA), or a salt thereof: (IA).

3. The oral composition of claim 1, wherein the compound is represented by formula (IB), or a salt thereof: (IB).

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

5. The oral composition of claim 4, wherein the plant extract is selected from the group consisting of: Guan Ye Ze Lan, ginger, North American spruce, Sichuan viburnum, arnica, sunflower, lettuce, thorn chrysanthemum, Sichuan wood fragrance, cloud wood fragrance, artemisia annua, soil Costus, bay laurel, Momordica charantia, patchouli, daisy family chrysanthemum, chicory, Canada goldenrod, barley, common wheat, corn malt bottle Grass, hairy grass, Paris polyphylla, tea, chrysanthemum, barley, millet, corn, Arabidopsis, Brachypodium distachyon, Puget Sound gum grass, Lobelia, Peanut, Indian pitcher plant, southern selaginella, Mandia yew, Acorus calamus, Andrographis paniculata, Artemisia seaweed, Bletilla striata, Polygonum multiflorum, upland cotton, Barley, Hypericum perforatum, wild banana, wild rice, rice, Spanish cork oak, potato, valerian, grape, polygonatum, Soybeans, switchgrass cultivar Pioneer, false yellow peel, Panax notoginseng procumbens, guava, rocket, senna Or Populus trichocarpa.

6. The oral composition of claim 4 or claim 5, wherein the plant extract further comprises a compound selected from the group consisting of: costunolide, 5a,9-dimethyl-3-methylene-3ah,4h,5h,9bh-naphtho[1,2-b]furan-2,8-dione, Baynol A, (3r,3ar,4r,11as)-3,6,10-trimethyl-2-oxo-3h,3ah,4h,7h,8h,11h,11ah-cyclodecano[b]furan-4-yl acetate, (3r,3as,4r,11as)-4-hydroxy-3,6,10-trimethyl-3h,3ah,4h,7h,8h,11h,11ah-cyclodecano[b]furan-2-one, (1 R ,2 S ,5 S ,6 S ,7 S )-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)propenal, 3,7,11-trimethyldodeca-1,3,5,8,10-pentaene, p-isopropyltoluene, (1S,2R,4R,7E,11S)-4,8-dimethyl-12-methylene-3,14-dioxatricyclo[9.3.0.02, 4]tetradec-7-en-13-one, 3-[(3aS,4R,5R,8aR)-4-hydroxy-5,7-dimethyl-3-methylene-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-dimethoxy chromen-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, (2 S ,3 S ,4 S ,5 R ,6 S )-6-[5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxochromen-3-yl]oxy-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid, 7-[(2 S ,3 R ,4 S ,5 S ,6 R )-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2 S ,3 R ,4 R ,5 R ,6 S )-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, 3-[(2 S ,3 R ,4 S ,5 S ,6 R )-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2 S ,3 R ,4 R ,5 R ,6 S )-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, 3-[(2 S ,5 R )-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2 S ,3 S ,5 R )-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, acetic acid [(2 R ,3 S ,4 S ,5 R ,6 S )-6-[3,5-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-8-methoxy-4-oxochromen-7-yl]oxy-3,4-dihydroxy-5-[(2 S ,3 R ,4 R ,5 R ,6 S )-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]methyl ester, 5,7-dihydroxy-2-(4-hydroxyphenyl)-3-[(2 S ,3 R ,4 S ,5 S )-3,4,5-trihydroxyoxacyclohexane-2-yl]oxychromen-4-one, 3-[(2 S ,3 R ,4 R ,5 S )-3,4-dihydroxy-5-(hydroxymethyl)oxan-2-yl]oxy-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one, (2 S ,3 S ,4 S ,5 R ,6 S )-6-[4-(5,7-dihydroxy-3,6-dimethoxy-4-oxochromen-2-yl)-2-hydroxyphenoxy]-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one, 1,6-dihydroxy-3-methyl-8-[(2 S ,3 R ,4 S ,5 S ,6 R )-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-methoxyphenyl)chromen-4-one, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[(2 S ,3 R ,4 S ,5 S ,6 R )-3,4,5-trihydroxy-6-(hydroxymethyl)oxacyclohexane-2-yl]oxychromen-4-one, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-6-methoxychromen-4-one, ( 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-enoamide, (1 S ,3 R ,4 R ,5 R )-3,4-double[[( 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. 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, or a pharmaceutical composition.

8. The oral composition according to any one of claims 1 to 7, wherein the dosage form of the oral composition is configured as one of a soft 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, wherein the oral composition further comprises an additive.

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

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

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

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

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

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

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

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

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

24. The oral composition of any one of claims 1 to 23, wherein the oral composition further comprises a compound of formula (II): (II) or a salt thereof, wherein R 1 is selected from 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; R 2 is selected from 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; R 3 is selected from 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; L is –Z 1 -Z 2 or –Z 1 -Z 2 -Z 3 ; Z1 is -CH2-, -O-, -NH-, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted C6 to C 10 aryl, optionally substituted -C3-C8 heterocyclic group or optionally substituted C3 to C 10 Heteroaryl, in some embodiments, Z1 is optionally substituted -C3-C8 heterocyclyl; 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 heterocyclic group or optionally substituted -C3-C 10 heteroaryl; and Z 3 is hydrogen, deuterium, halo, –CH2–, –O–, optionally substituted –C3-C8 cycloalkyl, optionally substituted –C6-C 10 aryl, optionally substituted -C3-C8 heterocyclic group or optionally substituted -C3-C 10 Heteroaryl.

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

26. The oral composition of any one of claims 1 to 25, wherein the oral composition further comprises a compound of formula (III) or a salt thereof: where R 1 is selected from 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; R 2 is selected from 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; R 3 is selected from 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; R 4 is selected from 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; L is –Z 1 -Z 2 or –Z 1 -Z 2 -Z 3 ; Z1 is -CH2-, -O-, -NH-, an optionally substituted C3-C8 cycloalkyl group, an optionally substituted C6 to C 10 aryl, optionally substituted -C3-C8 heterocyclic group or optionally substituted C3 to C 10 Heteroaryl, in some embodiments, Z1 is optionally substituted -C3-C8 heterocyclyl; 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 heterocyclic group or optionally substituted -C3-C 10 heteroaryl; and Z 3 is hydrogen, deuterium, halo, –CH2–, –O–, optionally substituted –C3-C8 cycloalkyl, optionally substituted –C6-C 10 aryl, optionally substituted -C3-C8 heterocyclic group or optionally substituted -C3-C 10 Heteroaryl.

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

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

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

30. A method of improving, restoring, regulating or maintaining sleep in a subject in need thereof, the method comprising: administering the oral composition according to any one of claims 1 to 29, wherein the oral composition is administered in an amount sufficient to improve, restore, regulate or maintain sleep in a subject in need thereof.

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

32. The method of claim 30 or claim 31 , wherein administering the oral composition also provides a reduction in calcium influx.

33. The method of any one of claims 30 to 32, wherein improving sleep provides the subject with a complete night's sleep.

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

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

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

37. The method of any one of claims 30 to 36, wherein regulating sleep reduces the subject's time to sleep.

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

39. The method of any one of claims 30 to 38, wherein modulating sleep increases the subject's average sleep length.

40. The method of claim 39, wherein the average sleep length increases from about 15 minutes to about 180 minutes.

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

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

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

44. The method of claim 42 or claim 43, wherein administering the oral composition also provides a reduction in calcium influx.

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 hypersomnias, circadian rhythm sleep-wake disorders, parasomnias, and sleep-related movement disorders.

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, nighttime eating (drinking) syndrome, jet lag, shift work sleep disorder, irregular sleep-wake patterns, confusional arousals, sleepwalking, sleep terrors, sleep talking, nightmares, sleep paralysis, REM sleep behavior disorder, snoring, and sleeping sickness.

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

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

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

50. The method of claim 49, wherein the additional compound treating the sleep disorder is selected from the group consisting of sedatives, hypnotics, anxiolytics, antipsychotics, antianxiety agents, antihistamines, benzodiazepines, barbiturates, cyclopyrrolones, GABA agonists, 5HT-2 antagonists, histamine antagonists, imidazopyridines, mild tranquilizers, melatonin agonists and antagonists, melatonergic agents, prokineticin agonists and antagonists, pyrazolopyrimidines, T-type calcium channel antagonists, triazolopyridines, melatonin, methylphenobarbital, meprobamate, methaqualone, methyperidone, midaflutol, midazolam, modafinil, naphthalene, phenobarbital, meprobamate, methaqualone, methyperidone ...zolam, modafinil, naphthalene, phenobarbital, meprobamate, meprobamate, methyperidone, midazolam, modafinil, naphthalene, phenobarbital, meprobamate, meprobamate, methyperidone, midazolam, modafinil, naphthalene, phenobarbital, meprobamate, meprobamate, methyperidone, midazolam, modafinil, naphthalene, phenobarbital, meprobamate, me Fazodone, NGD-2-73, nisolbamate, nitrazepam, nortriptyline, nortriptyline, oxazepam, paraldehyde, paroxetine, pentobarbital, perapine, perphenazine, phenelzine, phenobarbital, prazepam, promethazine, propofol, protriptyline, quazepam, ramelteon, reclozepam, cloletamide, secobarbital, sertraline, suprolone, TAK-375, temazepam, thioridazine, tiagabine, tracazolate, tranylcypromine, trazodone, triazolam, tripipam, trimethoprim-sulfamethoxazole, triclofossil, trifluoperazine, trimetozin, trimipramine, udazepam, venlafaxine, zaleplon, zolazepam, zopiclone, zolpidem, and combinations thereof.

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