Bioactive compositions and methods of use thereof

Abstract

The disclosed compositions, systems, and methods relate to compositions for human consumption and comprise a combination of paraxanthine and / or 1-methylxanthine and chlorogenic acid, and optionally other compounds that modulate the effect of the combination of paraxanthine and / or 1-methylxanthine and chlorogenic acid. Also disclosed are methods of using the aforementioned compositions to improve at least one of cognitive ability, mood, and / or sleep.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 63 / 434,206, filed on December 21, 2022, and entitled “BIOACTIVE COMPOSITIONS AND METHODS OF USE THEREOF,” the entire contents of which are incorporated herein by reference under 35 U.S.C. §119(e). Technical Field

[0003] The disclosed technology generally relates to compositions and methods for achieving physiological and / or cognitive function by administering compositions containing a combination of paraxanthine and chlorogenic acid. Background Art

[0004] Therefore, there is a need in the art to identify alternative compounds and mixtures thereof that can provide benefits. It is also desirable to provide compounds and mixtures thereof that can be used to provide multiple benefits, especially synergistic benefits. Summary of the Invention

[0005] Disclosed herein are compositions comprising paraxanthine and / or 1-methylxanthine and chlorogenic acid. In exemplary embodiments, the composition comprises from about 50 mg to about 400 mg of paraxanthine and / or 1-methylxanthine and at least about 25 mg of chlorogenic acid. In other embodiments, the composition comprises from about 25 mg to about 500 mg of chlorogenic acid. In other embodiments, the composition may further comprise one or more paraxanthine metabolites.

[0006] Also disclosed herein is a method of treating a condition in an individual in need thereof, which may comprise administering a composition disclosed herein to the individual. A method of enhancing the attention of an individual in need thereof may comprise administering a composition disclosed herein. A method of improving working memory in an individual in need thereof may comprise administering a composition to the individual, which composition may comprise a composition disclosed herein. A method of improving cognitive ability in an individual may comprise administering a composition disclosed herein. A method of preventing or treating TBI in an individual in need thereof. A method of treating an inflammatory disease or condition in an individual in need thereof. A method for improving joint health in an individual in need thereof. A method for enhancing neuroplasticity in an individual in need thereof. A method for improving digestive health in an individual in need thereof. A method of reducing hypertension in an individual in need thereof. A method of regulating cellular energy homeostasis may comprise administering a composition disclosed herein to the individual. A method of regulating blood glucose levels in an individual by administering a composition disclosed herein to the individual.

[0007] In certain embodiments, the disclosed compositions comprise another active ingredient selected from the group consisting of gallic acid, (+)-catechin (C), (-)-epicatechin (EC), (+)-gallocatechin (GC), (-)-epigallocatechin (EGC), (-)-catechin gallate (CG), (-)-gallocatechin gallate (GCG), (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG), glycerides, propylene glycol, Alcohol, lauroyl polyethylene glycol, lauroyl polyethylene glycol derivatives, piperine cocrystallized product, piperine, black pepper, bergamotin, dihydroxybergamotin (CYP3A4), flavonoids (naringin, hesperidin, nobiletin, tangeretin, quercetin), pterostilbene, fisetin, phospholipid complex, salicin, fish oil (omega-3 fatty acids and specific small lipid-promoting epoxide derivatives), oxidized lipids, tart cherry, krill oil, astaxanthin, proteolytic enzymes, glucosamine sulfate, chondroitin sulfate, MSM (Methylsulfonylmethane), SAMe (S-adenosylmethionine), ASU (Avocado-Soybean Unsaponifiable Fraction), Cetyl Myristoleate, Falcon, Triterpenes, Acaciacatechu, Andrographis paniculata, Scutalleria baicalensis, Agmatine Sulfate, Stinging Nettle, Sea Buckthorn, Curcumin, Cissus Quadrilangularis, Boswellia Serrata, Wasabi (Wasabi extract for tea tree oil), Emu Oil, Arnica, Mango (Mangifera indica L.(Anacardiaceae), Lagenaria breviflora, Ginger (Zingiberofficinale) (Ginger & Gingerols / Shogaols), Hoodia gordonii, Caffeine, Yohimbe, Methylsynephrine, Synephrine, Theobromine, Flavenoids, Tocopherols, Theophylline, Alpha-Yohimbe, Conjugated Linoleic Acid (CLA), Octopamine, Evodiamine, Passionflower, Red Pepper, Cayenne Pepper, Raspberry Ketones, Mukul Myrrh, Green Tea, Guarana, Kola Nut, Beta-Phenylethylamines, Acacia Rigidula, Forskolin (Coleus forskohlli), Theophylline, Synephrine, Yohimbe, Rhodiola Rosea, Ashwagandha, Ginseng, Ginkgo Biloba, Siberian Ginseng ginseng), astragalus, licorice, green tea, reishi mushroom, dehydroepiandrosterone (DHEA), pregnenolone, N-acetyl-tyrosine, glucuronolactone, acetyl-L-carnitine, 5-hydroxytryptophan, tryptophan, phenylethylamines, Sceletium tortuosum (and mesembrine alkaloids), Dendrobium sp.), Acacia, PQQ (pyrroloquinoline quinone), Ubiquinone (01), Nicotinamide Riboside, Picamiron, Huperzine A (Chinese stone pine) or Huperzia serrata, L-Dopa, Mucuna pruriens, Forskolin (Coleus forskohlii), 2-(Dimethylamino)ethanol (DMAE), DMAE bitartrate, Ornithine, Citrulline, Pyruvate, Eleutherococcus senticosus, D-Ribose, Whey Protein, Trimethylglycine, Arginine, HMB (β-Hydroxyβ-Methylbutyrate), Milk Protein, Schisandra chinensis, Leucine, Betaine, Leucic Acid, L-Carnitine, Sodium Bicarbonate, Arachidonic Acid, β-Alanine, Brassinosteroids, Cannabinoids, Alanylglutamine, Rhaponticum carthamoides), casein, ecdysteroids, creatine, branched-chain amino acids, beetroot, coffee, nitrates, Panax ginseng, clenbuterol, alpha-GPC, valine, colostrum, Trichopus zeylanicus, ashwagandha, Terminalia arjuna, eggs, ursolic acid, isoleucine, medium-chain triglycerides, glutamine, zinc, vitamin D, maca, schisandra chinensis, nicotinamide mononucleotide (NMN), exogenous ketones, ergothioneine, berberine, dihydroberberine, and combinations thereof.

[0008] In certain embodiments, the ratio of paraxanthine and / or 1-methylxanthine to chlorogenic acid administered to the individual is about 1:10 to about 1:30. In other embodiments, the ratio of paraxanthine to chlorogenic acid administered to the individual is about 1:10 to about 1:10.

[0009] In certain embodiments, the compositions are substantially free of caffeine.

[0010] Also disclosed herein is a method for improving cognitive function in an individual, comprising administering to the individual a composition comprising an effective amount of paraxanthine and chlorogenic acid. In certain embodiments, the improved cognitive function in the individual is measured by an increase in one or more of: attention, information acquisition, information processing, working memory, short-term memory, long-term memory, anterograde memory, retrograde memory, memory retrieval, discrimination learning, decision-making, inhibitory response control, attention set shifting, delayed reinforcement learning, reversal learning, temporal integration of autonomous behavior, processing speed, reasoning, problem solving, and / or social cognition. In certain embodiments, administering the composition to the individual enhances the individual's mood. In other embodiments, administration of paraxanthine and chlorogenic acid produces a synergistic enhancement of the individual's cognitive function relative to the administration of paraxanthine or chlorogenic acid alone.

[0011] Although a number of embodiments are disclosed, other embodiments of the present disclosure will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the disclosed compositions, systems, and methods. As will be appreciated, the disclosed compositions, systems, and methods are capable of modification in various obvious respects, all without departing from the spirit and scope of the present disclosure. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] none. DETAILED DESCRIPTION

[0013] Before explaining at least one embodiment of the present invention in detail, it should be understood that the present invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or shown in the accompanying drawings. The present invention is capable of other embodiments and can be practiced and implemented in various ways. Furthermore, it should be understood that the phraseology and terminology employed herein are for descriptive purposes only and should not be construed as limiting.

[0014] Ranges may be expressed herein as from "about" one particular value, and / or to "about" another particular value. When such a range is expressed, another aspect includes from the one particular value and / or to the other particular value. Similarly, when a value is expressed as an approximation by using the antecedent "about," it should be understood that the particular value forms another aspect. It should also be understood that the endpoints of each range are important, both in relation to and independent of the other endpoint. It should also be understood that many values are disclosed herein, and each value is also disclosed herein as "about" that particular value in addition to the value itself. For example, if the value "10" is disclosed, then "about 10" is also disclosed. It should also be understood that each unit between two particular units is also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0015] As used herein, the term "cardiovascular disease" or "cardiovascular disorder" is used herein in the broadest sense and includes all diseases and pathological conditions whose pathogenesis involves vascular abnormalities, such as, for example, atherosclerotic plaque formation (including stable or unstable / vulnerable plaques), atherosclerosis, arteriosclerosis, arteriolar sclerosis, and elevated systemic lipopolysaccharide (LPS) exposure. The term additionally includes diseases and pathological conditions that benefit from inhibition of atherosclerotic plaque formation. Cardiovascular disease includes, but is not limited to, coronary atherosclerosis, coronary microvascular disease, stroke, carotid artery disease, peripheral arterial disease, ischemia, coronary artery disease (CAD), acute coronary syndrome (ACS), coronary heart disease (CHD), conditions associated with CAD and CHD, cerebrovascular disease, peripheral vascular disease, aneurysms, vasculitis, venous thrombosis, diabetes and metabolic syndrome, chronic kidney disease, distal tissue damage after ischemia and reperfusion, and cardiopulmonary bypass. Specifically, included within this category are all cardiovascular diseases associated with conditions whose appearance, development, or progression can be controlled by inhibiting the formation of atherosclerotic plaques.

[0016] As used herein, "improving serum lipid profile" refers to lowering serum total and / or LDL cholesterol and triglyceride levels, and increasing the ratio of HDL cholesterol to LDL cholesterol.

[0017] Disclosed herein, in certain aspects, are methods of improving the serum lipid profile of a subject by administering an effective amount of one or more compositions disclosed herein.

[0018] The term "overweight" is defined as a person who has a body weight greater than or equal to 25 kg / m 2 and less than 30 kg / m 2 The terms "overweight" and "preobesity" are used interchangeably.

[0019] As used herein, the term "obese" is defined as a condition in which an individual has a body weight equal to or greater than 30 kg / m 2 According to WHO, the term obesity can be classified as follows: The term "type I obesity" refers to a condition in which the BMI is equal to or greater than 30 kg / m 2 But less than 35 kg / m 2 The term "type II obesity" refers to a condition in which the BMI is equal to or greater than 35 kg / m 2 But less than 40 kg / m 2 The term "type III obesity" refers to a condition in which the BMI is equal to or greater than 40 kg / m 2 situation.

[0020] As used herein, the terms "management" and "managing" encompass preventing, delaying the recurrence of, or lessening the severity of the recurrence of a disease, disorder, or condition in a patient already suffering from a fat-related body composition or weight disorder such as obesity, lipodystrophy, diabetes or metabolic syndrome, fibrosis, and cancer. The terms encompass modulating the onset, development, and / or duration of a fat-related body composition or weight disorder such as obesity, lipodystrophy, diabetes or metabolic syndrome, fibrosis, and cancer, or changing the way a patient responds to a fat-related body composition or weight disorder.

[0021] As used herein, the term "subject" refers to the target of administration, such as an animal. Thus, the subject of the methods disclosed herein can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig, or rodent. The term does not denote a particular age or sex. Thus, adult and newborn individuals, as well as fetuses, whether male or female, are intended to be covered. In one aspect, the subject is a mammal. A patient refers to an individual suffering from a disease or disorder. As used herein, the term "treatment" refers to the medical management of a patient with the purpose of curing, improving, stabilizing, or preventing a disease, pathological condition, or disorder. The term includes active treatment, i.e., treatment specifically intended to improve a disease, pathological condition, or disorder, and also includes causal treatment, i.e., treatment intended to remove the cause of the associated disease, pathological condition, or disorder. In addition, the term includes palliative treatment, i.e., treatment designed to relieve symptoms rather than cure a disease, pathological condition, or disorder; preventive treatment, i.e., treatment intended to minimize or partially or completely inhibit the development of an associated disease, pathological condition, or disorder; and supportive treatment, i.e., treatment for supplementing another specific therapy intended to improve an associated disease, pathological condition, or disorder. In various aspects, the term encompasses any treatment of an individual, including mammals (e.g., humans), and includes: (i) preventing the disease from occurring in an individual who may be susceptible to the disease but has not yet been diagnosed with the disease; (ii) suppressing the disease, i.e., preventing its development; or (iii) alleviating the disease, i.e., causing the disease to regress. In one aspect, the individual is a mammal such as a primate, and in another aspect, the individual is a human.

[0022] The term "subject" also includes domesticated animals (eg, cats, dogs, etc.), livestock (eg, cows, horses, pigs, sheep, goats, etc.), and laboratory animals (eg, mice, rabbits, rats, guinea pigs, fruit flies, etc.).

[0023] As used herein, the terms "effective amount" and "effective amount" refer to an amount sufficient to achieve a desired result or have a certain effect on an undesirable condition. For example, a "therapeutically effective amount" refers to an amount sufficient to achieve the desired therapeutic result or have a certain effect on an undesirable symptom, but generally insufficient to cause unacceptable adverse side effects. The specific therapeutically effective dosage level for any particular patient will depend on a variety of factors, including the disorder being treated and the severity of the disorder; the specific composition employed; the patient's age, weight, general health, sex, and diet; the time of administration; the route of administration; the excretion rate of the specific compound employed; the duration of treatment; drugs used in combination or concomitantly with the specific compound employed, and similar factors well known in the medical art. For example, it is well within the skill of the art to start the dose of the compound at a level lower than that required to achieve the desired therapeutic effect and gradually increase the dose until the desired effect is achieved. If desired, the effective daily dose can be divided into multiple doses for administration purposes. Thus, a single-dose composition may contain such an amount or a submultiple thereof to make up the daily dose. In the presence of any contraindications, the dose can be adjusted by the individual physician. Dosages can vary and can be administered in one or more doses per day, for one or more days. Guidance on appropriate dosages for a given class of pharmaceutical products can be found in the literature. In various other aspects, the formulation can be administered in a "prophylactically effective amount"; that is, an amount effective to prevent a disease or condition.

[0024] As used herein, the term "synergistic effect" or grammatical variations thereof refers to and includes the synergistic effect encountered in a combination of two or more active compounds, wherein the combined activity of the two or more active compounds exceeds the sum of the individual activities of each active compound.

[0025] As used herein, the term "synergistically effective amount" refers to and includes an amount of two or more active compounds that provides the synergistic effect described above.

[0026] As used herein, the term "substantially" refers to the complete or nearly complete extent or degree of an action, characteristic, property, state, structure, item, or result. For example, an object that is "substantially" enclosed will mean that the object is either completely enclosed or nearly completely enclosed. The exact permissible degree of deviation from absolute completeness may in some cases depend on the specific context. However, in general, the proximity of completion will be such as to have the same overall result as if absolute and complete completion were achieved. The use of "substantially" also applies when used in a negative sense to refer to the complete or nearly complete lack of an action, characteristic, property, state, structure, item, or result. For example, a composition that is "substantially free" of particles will completely lack particles, or be so close to completely lacking particles that the effect will be the same as if it completely lacked particles. In other words, a composition that is "substantially free" of a component or element may still actually contain these items, as long as there is no measurable effect thereof.

[0027] As used herein, "cognitive function" refers to any higher-order intellectual brain process or brain state involved in learning and / or memory, including but not limited to attention, information acquisition, information processing, working memory, short-term memory, long-term memory, anterograde memory, retrograde memory, memory retrieval, discrimination learning, decision-making, inhibitory response control, attention set shifting, delayed reinforcement learning, reversal learning, temporal integration of autonomous behavior, expressing interest in the surrounding environment, self-care processing speed, reasoning, problem solving, and social cognition.

[0028] Composition

[0029] Disclosed are compositions comprising a combination of paraxanthine and chlorogenic acid and related uses thereof. Paraxanthine can be produced synthetically or isolated from natural sources or by fermentation. Paraxanthine isolated from these sources can be purified to a purity of 95% or greater. Optionally, a lower purification can be used such that the paraxanthine combination comprises 50% or even less of the material. In some embodiments, it may be preferred to utilize paraxanthine isolated from a natural source, which may contain other paraxanthine congeners typically present in the source of paraxanthine.

[0030] Further disclosed are compositions comprising a combination of 1-methylxanthine (also referred to herein as "1-Mx") and chlorogenic acid, and related uses thereof. 1-Methylxanthine can be produced synthetically, or can be isolated from natural sources or by fermentation. 1-Methylxanthine isolated from these sources can be purified to a purity of 95% or greater. Optionally, a lower purification can be used such that the paraxanthine combination comprises 50% or even less of the material. In some embodiments, it may be preferred to utilize 1-methylxanthine isolated from a natural source, which may include other 1-methylxanthine congeners that are typically present in the source of 1-methylxanthine.

[0031] In certain embodiments, the composition is formulated such that a dose contains from about 1 to about 1000 mg of paraxanthine and / or 1-methylxanthine (e.g., about 1 mg, about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 75 mg, 100, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, or about 1000 mg, etc., or any range or value therein).

[0032] Chlorogenic acid is a polyphenol that is an ester of caffeic acid and quinic acid. Chlorogenic acid scavenges free radicals, thereby inhibiting DNA damage and preventing the induction of carcinogenesis. The chemical formula of CA is C 16 H 18 According to certain embodiments, chlorogenic acid has the following structure:

[0033]

[0034] In certain embodiments, the composition is formulated so that a dose contains from about 25 to about 1000 mg of chlorogenic acid (e.g., about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 75 mg, 100, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, or about 1000 mg, etc., or any range or value therein).

[0035] In certain embodiments, the combination of paraxanthine and / or 1-methylxanthine and chlorogenic acid can be combined with one or more other compounds (e.g., other active ingredients) to provide a variety of positive effects in an individual. By varying the combination of paraxanthine and chlorogenic acid and / or the dosage of the compound combined therewith, a variety of physiological effects can be selected. The composition can primarily provide a single benefit, or can provide multiple benefits simultaneously.In certain embodiments, the combination of paraxanthine and chlorogenic acid is combined with one or more additional active ingredients selected from the group consisting of gallic acid, (+)-catechin (C), (-)-epicatechin (EC), (+)-gallocatechin (GC), (-)-epigallocatechin (EGC), (-)-catechin gallate (CG), (-)-gallocatechin gallate (GCG), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG). , glycerides, propylene glycol, lauroyl polyethylene glycol, lauroyl polyethylene glycol derivatives, piperine co-crystallized products, piperine, black pepper, bergamotin, dihydroxybergamotin (CYP3A4), flavonoids (naringin, hesperidin, nobiletin, tangerin, quercetin), pterostilbene, fisetin, phospholipid complex, salicin, fish oil (omega-3 fatty acids and specific small lipid-promoting epoxide derivatives), oxidized lipids, tart cherry, krill oil, astaxanthin, proteolytic enzymes, glucosamine sulfate, chondroitin sulfate, MSM (methylsulfonylmethane), SAMe (S-adenosylmethionine), ASU (Avocado-Soy Unsaponifiable Fraction), Cetyl Myristate, Falcon, Triterpenes, Catechu, Andrographis Paniculata, Scutellaria Baicalensis, Agmatine Sulfate, Stinging Nettle, Sea Buckthorn, Curcumin, Pueraria Quadrangularis, Frankincense, Wasabi (Wasabi Extract for Tea Tree Oil), Emu Oil, Arnica Montana, Mango (Anacardiaceae), Ginger (Zingiber Officinale & Gingerols / Shogaols), Cuphead Cornus officinalis, Caffeine, Yohimbe, Methylsynephrine, Synephrine, Theobromine, Tocopherols, Theophylline, Alpha-Yohimbe, Conjugated Linoleic Acid (CLA), Octopamine, Evodiamine, Passionflower, Red Pepper, cayenne pepper, raspberry ketones, myrrh mukul, green tea, guarana, kola nut, beta-phenylethylamines, acacia, forskolin (Coleus forskohlii), theophylline, synephrine, yohimbe, rhodiola rosea, ashwagandha, ginseng, ginkgo biloba, Siberian ginseng, astragalus, licorice, green tea, reishi mushroom, dehydroepiandrosterone (DHEA), pregnenolone, N-acetyl-tyrosine, glucuronolactone, acetyl-L-carnitine, 5-hydroxytryptophan, tryptophan, phenylethylamines, mesembryanthemum contortum (and mesembryanthemum alkaloids), dendrobium, acacia, PQQ (pyrroloquinoline quinone), ubiquinone (01), nicotinamide riboside, picamiron, huperzine A (Chinese club moss) or huperzine serrata, L-dopa, Mucuna pruriens, forskolin (Coleus forskohlii), 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, medium chain triglycerides, creatine, citrulline, arginine, lion's mane, cordyceps, leucine, isoleucine, valine, BAIBA, ergothioneine, seed of paradise, Kanna, huperzine A, ketones, maca, ginseng, ashwagandha, rhodiola rosea, theanine, and combinations thereof.

[0036] In certain embodiments, paraxanthine and chlorogenic acid are present in approximately equal amounts. In these embodiments, paraxanthine and chlorogenic acid each comprise approximately 50% of the total weight of paraxanthine and chlorogenic acid in the composition, on a w / v basis. In certain other embodiments, the ranges may be at least 10% to 90% paraxanthine and 90% to 10% chlorogenic acid, respectively.

[0037] In other embodiments, paraxanthine and chlorogenic acid are present in a ratio of 1 :4 to about 1 :30. In other embodiments, paraxanthine and chlorogenic acid are present in a ratio of about 1 :4 to about 1 :10.

[0038] In certain embodiments, 1-methylxanthine and chlorogenic acid are present in approximately equal amounts. In these embodiments, 1-methylxanthine and chlorogenic acid each comprise approximately 50% of the total weight of 1-methylxanthine and chlorogenic acid in the composition, on a w / v basis. In certain other embodiments, the ranges may be at least 10% to 90% 1-methylxanthine and 90% to 10% chlorogenic acid, respectively.

[0039] In other embodiments, 1-methylxanthine and chlorogenic acid are present in a ratio of 1:4 to about 1:30. In other embodiments, 1-methylxanthine and chlorogenic acid are present in a ratio of about 1:4 to about 1:10.

[0040] In certain embodiments, chlorogenic acid is administered to a subject at a dose of about 100-150 mg / kg of the subject's body weight.

[0041] In certain embodiments, the composition is formulated so that a dose contains from about 1 to about 1000 mg of paraxanthine (e.g., about 1 mg, about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 75 mg, 100, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, or about 1000 mg, etc., or any range or value therein).

[0042] In certain embodiments, the composition is formulated such that a dose contains from about 500 to about 13,500 mg of chlorogenic acid (e.g., about 500 mg, about 1000 mg, about 1,500 mg, about 2,000 mg, about 2,500 mg, about 3,000 mg, about 3,500 mg, about 4,0000 mg, about 4,500 mg, about 5,000 mg, about 7,500 mg, 10,000, about 13,500 mg, etc., or any range or value therein).

[0043] According to individuality to be treated and route of administration, the compounds of the present invention can be used in different doses. Although dosage varies because of individuality, suitable daily dose ranges are each individual about 1 to about 1000 mg (for example, about 1 mg, about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 75 mg, 100, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg or about 1000 mg etc., or any range or value therein), with single dose or multiple dose.

[0044] In certain embodiments, the composition is formulated so that a dose contains from about 1 to about 1000 mg (e.g., about 1 mg, about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 75 mg, 100, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, or about 1000 mg, etc., or any range or value therein) of paraxanthine and from about 400 to about 3000 mg (e.g., about 400 mg, about 450 mg, about 500 mg, about 550 mg, mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1500 mg, about 2000 mg, about 2500 mg or about 3000 mg, etc., or any range or value therein).

[0045] In certain embodiments, the composition is formulated such that each dose contains from about 1 to about 1000 mg (e.g., about 1 mg, about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 75 mg, 100, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, or about 1000 mg, etc., or any range or value therein) of 1-methylxanthine and from 400 to about 3000 mg (e.g., about 400 mg, about 450 mg, about 500 mg, about 550 mg, mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1500 mg, about 2000 mg, about 2500 mg or about 3000 mg, etc., or any range or value therein).

[0046] nutritional supplements

[0047] The compositions of the present disclosure may take the form of a dietary supplement, or they may themselves be used in combination with a dietary supplement (also referred to herein as a food supplement).

[0048] Nutritional supplements can come in many forms, such as tablets, capsules, soft gels, gel caps, liquids, or powders. Some dietary supplements can help ensure adequate dietary intake of essential nutrients; others may help reduce the risk of disease.

[0049] Food products

[0050] Compositions of the present disclosure can take the form of food products. Here, the term "food" is broad and includes food and drink for humans, as well as food and drink (i.e., feed) for animals. Preferably, the food product is suitable for and designed for human consumption.

[0051] Depending on the use and / or mode of application and / or mode of administration, the food may be in the form of a liquid, a solid or a suspension.

[0052] When in the form of a food product, the composition may comprise one or more of the following or be used in combination with one or more of the following: a nutritionally acceptable carrier, a nutritionally acceptable diluent, a nutritionally acceptable excipient, a nutritionally acceptable adjuvant, a nutritionally active ingredient.

[0053] For example, the composition of the present disclosure can take the form of one of the following: a juice; a beverage containing whey protein; a health tea or herbal tea, a cocoa beverage, a coffee beverage, a yogurt and / or a beverage yogurt, a cheese, an ice cream, a dessert, a candy, a cookie, a cake, a cake mix or cake filling, a snack food, a fruit filling, a cake or donut frosting, a ready-to-eat bakery filling cream, a cookie filling, a ready-to-use bakery filling, a reduced-calorie filling, an adult nutritional beverage, an acidified soy / juice beverage, a nutritional or health bar, a beverage powder, an energy drink, a sublingual, a gummy, a calcium-fortified soy milk, or a calcium-fortified coffee beverage.

[0054] Food ingredients

[0055] The compositions of the present disclosure may take the form of a food ingredient and / or a feed ingredient.

[0056] As used herein, the term "food ingredient" or "feed ingredient" includes a composition that is a functional food or food product that is a nutritional and / or health supplement for humans and animals or a composition that can be added to a functional food or food product that is a nutritional and / or health supplement for humans and animals.

[0057] Depending on the use and / or the mode of application and / or the mode of administration, the food ingredient may be in the form of a liquid, a suspension or a solid.

[0058] Functional foods

[0059] The compositions of the present disclosure may take the form of functional foods.As used herein, the term "functional food" means a food that is not only capable of providing a nutritional effect, but is also capable of delivering additional beneficial effects to the consumer.

[0060] Thus, a functional food is a conventional food that has components or ingredients (such as those described herein) incorporated therein that impart a specific functional effect—such as a medical or physiological benefit—to the food rather than a purely nutritional effect.

[0061] While there is no legal definition of functional foods, most parties involved in the field agree that they are foods marketed as having specific health benefits beyond basic nutritional effects.

[0062] Some functional foods are nutraceuticals. Here, the term "nutraceutical" means a food that not only provides nutritional benefits and / or flavor satisfaction, but also delivers a therapeutic (or other beneficial) effect to the consumer. Nutraceuticals straddle the traditional dividing line between food and medicine.

[0063] Medical food

[0064] The compositions of the present disclosure may take the form of a medical food. "Medical food" means a food that is formulated to be consumed or administered with or without a physician's supervision and is intended for use in a specific dietary management or condition for which unique nutritional requirements have been established through medical evaluation based on generally accepted scientific principles.

[0065] How to use

[0066] In certain embodiments, paraxanthine can be combined with chlorogenic acid, and in certain embodiments, can be combined with one or more other compounds (e.g., other active ingredients) to provide a variety of positive effects in individuals. By changing the dosage of paraxanthine and / or the compound combined therewith, various physiological effects can be selected. The composition can primarily provide one benefit, or can provide multiple benefits simultaneously. Depending on the individual to be treated and the route of administration, the compounds of the present invention can be administered in different doses. Although the dosage will vary from subject to subject, a suitable daily dosage range is from about 1 to about 1000 mg per subject (e.g., about 1 mg, about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 75 mg, 100, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg or about 1000 mg, etc., or any range or value therein), administered in single or multiple doses.

[0067] Advantageously, the compositions of the present disclosure can be administered in a single dose, e.g., once a day or less, or in a total daily dose administered in divided doses twice, three times, or four times a day. In certain embodiments, the compositions are administered as needed (e.g., when an individual needs to enhance energy, motor or cognitive performance, etc.).

[0068] Athletic performance

[0069] Further disclosed herein is a method for enhancing individual performance or energy, comprising administering a composition disclosed herein to an individual. As used herein, the term "enhanced performance" is intended to represent any improvement in performance. Performance can be assessed in any manner. Certain enhancements are easily measured. For example, in timed events, the improved time can assess the enhanced performance. Certain performance enhancement properties can be subjectively judged by an athlete, performer, or observer. In these cases, enhanced performance means that performance is subjectively perceived as improved, amplified, faster, better, etc. In certain embodiments, the disclosed method is used to enhance athletic performance. "Athletic performance" refers to any occupation or recreational activity in which the performer, such as an athlete, performs physical activities such as running, swimming, golf, bowling, archery, rugby, baseball, basketball, football, hiking, cycling, dancing, etc. In some cases, athletic performance is improved by improving individual endurance. In other words, administering the disclosed composition improves individual endurance levels, thereby enhancing individual athletic performance. In further embodiments, administering the composition to an individual increases cognitive ability, thereby improving athletic performance.

[0070] In certain embodiments, upon administration of the composition, the individual experiences an improvement in at least one of mood, energy, concentration, attention, or sexual desire, or a decrease in at least one of anxiety, fatigue, perception of effort, or perception of pain.

[0071] In further embodiments, following continued administration to an individual, the composition does not produce dependence in the individual and / or produce withdrawal effects in the individual when continued use is discontinued.

[0072] Further disclosed herein is a method of increasing exercise tolerance in an individual, comprising administering a composition disclosed herein to the individual. In certain embodiments, the composition administered to the individual comprises paraxanthine and chlorogenic acid. In an exemplary embodiment, administration of paraxanthine and chlorogenic acid produces a synergistic increase in exercise tolerance in the individual relative to administration of either paraxanthine or chlorogenic acid alone.

[0073] Further disclosed herein is a method of increasing exercise tolerance in an individual, comprising administering a composition disclosed herein to the individual. In certain embodiments, the composition administered to the individual comprises paraxanthine and chlorogenic acid. In an exemplary embodiment, administration of paraxanthine and chlorogenic acid produces a synergistic increase in exercise tolerance in the individual relative to administration of either paraxanthine or chlorogenic acid alone.

[0074] According to further embodiments, administering the disclosed composition to an individual increases the energy level perceived by the individual. In an exemplary embodiment, the individual experiences an increase in energy of at least about 5%. According to certain embodiments, the administered composition further comprises (in addition to paraxanthine and / or 1-methylxanthine and / or chlorogenic acid) at least one ingredient selected from the group consisting of L-theanine, phosphatidylcholine, α-GPC (L-α-glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, Bacopa monnieri, phosphatidylserine, pilocarpine, and cevimeline Amburana cearensis, Lippia sidoides, Guarana, Plathymiscium truncatum, and ciprofloxacin. floribundum), tetrahydrocurcumin and Solanum nigrum and / or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, huperzine A, theacrine, O(2), 1,7,9-tetramethyluric acid (methylliberine), B12, sulbutiamine, magnolia bark, ketones, MCTs, omega 3, lutein, zeaxanthin and N-acetyl-tyrosine, acetyl-L-carnitine and / or combinations thereof.

[0075] In certain embodiments, the individual's perceived energy level increases by about 2% to about 50%. In further embodiments, the individual's perceived energy level increases by about 5% to about 30%. In yet further embodiments, the individual's perceived energy level increases by about 10% to about 25%.

[0076] Improving lipid profile and treating CVD

[0077] Disclosed herein is a method for improving the serum lipid profile of an individual, the method comprising administering to the individual an effective amount of a composition comprising from about 2 mg to about 800 mg of paraxanthine and from about 25 mg to about 500 mg of chlorogenic acid. In certain aspects, the paraxanthine is present in the composition in an amount from about 20 mg to about 600 mg. In other aspects, the paraxanthine is present in the composition in an amount from about 50 mg to about 400 mg.

[0078] In another aspect, a method for preventing or treating a cardiovascular condition is provided, the condition including the pathology of atherosclerotic plaque formation. The method comprises administering to an individual in need thereof a therapeutically effective amount of a composition comprising from about 2 mg to about 800 mg of paraxanthine and from about 25 mg to about 500 mg of chlorogenic acid. Cardiovascular conditions include, for example, coronary artery disease, coronary microvascular disease, stroke, carotid artery disease, peripheral arterial disease, and chronic kidney disease. The method may include further slowing the progression of atherosclerotic plaque formation. The method may further comprise administering to the individual one or more additional therapeutic agents for preventing or treating the cardiovascular condition.

[0079] In another aspect, a method for treating metabolic syndrome is provided. The method comprises administering to an individual in need thereof a therapeutically effective amount of a composition comprising from about 2 mg to about 800 mg of paraxanthine and from about 25 mg to about 500 mg of chlorogenic acid. The method may further comprise reducing one or more risk factors associated with metabolic syndrome, including one or more of abdominal obesity, hyperglycemia, dyslipidemia, and hypertension. The method may further comprise administering to the individual one or more additional agents to prevent or treat metabolic syndrome.

[0080] In another aspect, a method for delaying or slowing the progression of atherosclerosis is provided, comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising about 2 mg to about 800 mg of paraxanthine and about 25 mg to about 500 mg of chlorogenic acid.

[0081] Weight loss / body composition

[0082] Paraxanthine exhibits a variety of effects depending on the dosage. The presence of other ingredients may also modulate its effects. It can be used to improve lipolysis, thermogenesis and / or reduce appetite. In one embodiment, paraxanthine can be used to promote weight loss by reducing appetite, acting as an antioxidant and anti-inflammatory agent. Paraxanthine can be used transdermally to enhance one or more of these effects. In another embodiment, a dietary supplement is provided, comprising from about 2 mg to about 800 mg of paraxanthine and from about 25 mg to about 500 mg of chlorogenic acid. In another embodiment, a nutritional supplement is provided, which supports weight loss and / or fat loss through lipolysis to improve body composition. Therefore, one object of the present disclosure is to provide a composition comprising paraxanthine that can impart a variety of positive effects on an individual's body composition. Another object of the present disclosure is to provide homologues, derivatives and repeats of paraxanthine and synthetic chemical equivalents of paraxanthine. Another object of the present disclosure is to provide aggregated paraxanthine, paraxanthine salts, microencapsulated, liposomal or esterified paraxanthine. Another object of the present disclosure is to provide paraxanthine in combination with glycerides of paraxanthine, propylene glycol, polyethylene glycol (PEG), lauroyl polyethylene glycol, lauroyl polyethylene glycol derivatives, and co-crystallized products.

[0083] Further disclosed herein is a method of promoting weight loss and / or weight management in an individual by providing to the individual a composition comprising from about 2 mg to about 800 mg of paraxanthine.

[0014] Although dosage varies from individual to individual, suitable daily dosage ranges from about 1 to about 1000 mg per individual (e.g., about 1 mg, about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 75 mg, 100, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg or about 1000 mg, etc., or any range or value therein), are administered in single dose or multiple doses. In some aspects, paraxanthine is present in the compositions in an amount of about 20 mg to about 600 mg. In other aspects, paraxanthine is present in the composition in an amount from about 50 mg to about 400 mg.

[0084] According to certain embodiments, weight loss is promoted by inducing thermogenesis in an individual. According to exemplary embodiments of these embodiments, the composition may further comprise one or more compounds selected from the group consisting of caffeine, green tea, capsaicin, garcinia cambogia, yohimbine, catechol, EGCG, catechins, proanthocyanidins, octacosanol, and bitter orange.

[0085] According to further embodiments, weight loss is promoted by suppressing the individual's appetite. In exemplary embodiments of these embodiments, the composition may further comprise one or more compounds selected from the group consisting of fenugreek, glucomannan, gymnema sylvestre, 5-HTP, Caralluma fimbriata, green tea extract, conjugated linoleic acid, garcinia cambogia, and yerba mate.

[0086] According to further embodiments, weight loss is promoted by enhancing lipolysis in an individual. In exemplary embodiments of these embodiments, the composition may further comprise one or more compounds selected from the group consisting of caffeine, green tea extract, L-carnitine, garcinia cambogia (hydroxycitric acid), capsaicin, ginseng, taurine, silk peptide, catechol, EGCG, catechins, proanthocyanidins, octacosanol, and octacosanol.

[0087] According to certain embodiments, the disclosed methods further comprise restricting caloric intake of the individual. In exemplary embodiments, the individual loses more weight than a comparable calorie-restricted individual who has not been provided with the composition. According to further embodiments, the ratio of fat loss to muscle loss in the individual is greater than a comparable calorie-restricted individual who has not been provided with the composition.

[0088] Suppress inflammation

[0089] Also disclosed herein is a method of inhibiting inflammation in an individual in need thereof, comprising administering to the individual a composition comprising: about 2 mg to about 800 mg of paraxanthine and about 25 mg to about 500 mg of chlorogenic acid. In certain aspects, the paraxanthine is present in the composition in an amount of about 20 mg to about 600 mg. In other aspects, the paraxanthine is present in the composition in an amount of about 50 mg to about 400 mg.

[0090] In certain embodiments, the individual is at risk for an inflammatory disease or condition. In further embodiments, the individual is diagnosed with an inflammatory disease or condition. In exemplary embodiments, the individual is diagnosed with diabetes, Crohn's disease, rheumatoid arthritis, fibromyalgia, systemic lupus erythematosus, glomerulonephritis, scleroderma, or multiple sclerosis.

[0091] In still further embodiments, the one or more additional ingredients are selected from omega-3 fatty acids, vitamin D, vitamin B, protein, selenium, rapidly digestible carbohydrates such as sugars, vitamin K, calcium, vitamin A, ashwagandha (Withania somnifera), acetylcholine, acetyl-L-carnitine, tyrosine, N-acetyl-L-tyrosine, ergothioneine, tryptophan, 5-HTP, arginine, citrulline, norvaline, GABA, DOPA (Velvet Bean), Kanna (serotonin), L-theanine, phosphatidylcholine, alpha-GPC (L-alpha-glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, Bacopa monnieri, phosphatidylserine, pilocarpine and cevimeline, Alara dal, Lipidium officinale, guarana, Gradiocarpus multiflorus, tetrahydrocurcumin, and Solanum nigrum.

[0092] Also disclosed herein are methods of improving joint health by administering a composition comprising paraxanthine to an individual in need thereof. In certain embodiments, the composition further comprises dileucine.

[0093] According to certain embodiments, improving joint health comprises alleviating or reducing the severity of at least one symptom of osteoarthritis, such as, for example, pain, stiffness, tenderness, decreased flexibility, friction, bone spurs, swelling, or any combination thereof. Thus, in some embodiments, a method of reducing the severity of at least one symptom of osteoarthritis in an individual suffering from osteoarthritis is provided, comprising administering to the individual an herbal composition of the present disclosure.

[0094] In some embodiments of the fourth aspect, the improvement in joint health can be measured by the change from baseline to endpoint score in the 30-second sit-to-stand test (30SCST). Thus, in some embodiments, a method of improving the 30-second sit-to-stand test (30SCST) score in an individual with an inflammatory joint condition is provided, comprising administering a composition of the present disclosure to the individual for at least 30 days, at least 60 days, at least 90 days, at least 120 days, or longer. In some embodiments, the improvement in 30SCST at 120 days is at least 8%, at least 10%, at least 13%, at least 15%, at least 16%, or at least about 18%.

[0095] In some embodiments of the fourth aspect, the improvement in joint health can be measured by the change in knee flexion range of motion from baseline to endpoint. Thus, in some embodiments, a method of improving knee flexion range of motion in an individual with an inflammatory joint condition is provided, comprising administering a composition of the present disclosure to the individual for at least 30 days, at least 60 days, at least 90 days, at least 120 days, or longer. In some embodiments, the improvement in knee flexion range of motion at 120 days is at least 4%, at least 5%, at least 6%, or at least 7%.

[0096] As described herein, an effective amount of the composition can be administered to an individual once daily. In some embodiments, an effective amount of the composition can be administered to an individual in multiple doses per day, for example, twice a day or more frequently, three times a day or more frequently, or four times a day or more frequently. In some embodiments, an effective amount of the composition can be administered to an individual once a week or more frequently, twice a week or more frequently, three times a week or more frequently, four times a week or more frequently, five times a week or more frequently, or six times a week or more frequently.

[0097] Cognitive function

[0098] Disclosed herein is a method of enhancing cognitive function in an individual, comprising administering to the individual a composition disclosed herein. In certain embodiments, the improved cognitive function is measured by an increase in one or more of: attention, information acquisition, information processing, working memory, short-term memory, long-term memory, anterograde memory, retrograde memory, memory retrieval, discrimination learning, decision-making, inhibitory response control, attentional set shifting, delayed reinforcement learning, reversal learning, temporal integration of voluntary behavior, processing speed, reasoning, problem solving, and / or social cognition.

[0099] In certain embodiments, administration of the disclosed compositions increases working memory.

[0100] In other embodiments, administration of the disclosed compositions increases attention.

[0101] According to certain embodiments, the composition of the method disclosed herein for enhancing cognitive function further comprises N-acetyl-tyrosine, taurine, huperzine A, acetyl-L-carnitine, CDP choline, α-GPC, choline bitartrate, choline citrate, B12, caffeine, O(2),1,7,9-tetramethyluric acid, 1,3,7,9-tetramethyluric acid, paraxanthine, theobromine, ashwagandha, rhodiola rosea, lutein, zeaxanthin, fish oil, creatine, ginseng, lion's mane mushroom, niacin, cordyceps, theanine, B vitamins, GABA, sulbutiamine, vinpocetine, adenosine triphosphate, inositol, enhanced arginine silicate, nitrates, electrolytes, hesperidin and derivatives of hesperidin and / or Bacopa monnieri.

[0102] In certain embodiments, the individual experiences age-related cognitive decline. In an exemplary embodiment, administering the composition to an individual will increase the BDNF level in the individual. According to certain embodiments, administering the composition to an individual will increase the brain-derived neurotrophic factor (BDNF) level in the individual. In an exemplary embodiment, the BDNF level increases by about 5% to about 40%. In a further embodiment, the BDNF level increases by at least about 15%. In a further embodiment, administering the composition to an individual will increase other neurotrophic factors, such as neuron growth factor (NGF).

[0103] Treatment

[0104] Also disclosed herein is a method of treating a condition in a subject by administering a composition disclosed herein to a subject in need thereof. In certain embodiments, the condition is selected from narcolepsy, epilepsy, attention deficit disorder, attention deficit hyperactivity disorder (ADHD), cognitive impairment, paralysis, uncontrolled anger, migraine, substance abuse addiction, eating disorders, depression, anxiety, traumatic head injury (TBI), Parkinson's disease, Alzheimer's disease, and dementia.

[0105] Further disclosed herein is a method for treating a mood disorder by administering a composition disclosed herein to an individual in need thereof. In certain embodiments, the mood disorder is selected from clinical depression, postpartum depression (postnataldepression) or postpartum depression (postpartum depression), perinatal depression, atypical depression, melancholic depression (melancholic depression), psychotic major depression, catatonic depression (catatonic depression), seasonal affective disorder, dysthymia, double depression, depressive personality disorder, recurrent brief depression, mild depression, bipolar disorder or manic depression, depression caused by chronic medical conditions, comorbid depression (comorbid depression), treatment-resistant depression, refractory depression, suicidal tendency, suicidal ideation (suicidal ideation) or suicidal behavior. In some embodiments, the methods described herein provide a therapeutic effect to an individual suffering from depression (e.g., moderate or severe depression). In some embodiments, the mood disorder is related to a disease or condition as described herein.

[0106] In certain embodiments, the mood disorder is depression.In exemplary embodiments, the individual has been diagnosed with or is at risk for depression.

[0107] Further disclosed herein are methods for treating an anxiety disorder in an individual in need thereof by administering to an individual in need thereof a composition disclosed herein. In certain embodiments, the anxiety disorder is selected from the group consisting of generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, phobia, and post-traumatic stress disorder. As will be understood by those skilled in the art, anxiety disorder is an umbrella term encompassing several different forms of abnormal and pathological fear and anxiety.

[0108] According to certain embodiments, the composition is administered in a therapeutically effective amount. In other embodiments, the composition is administered in a prophylactically effective amount.

[0109] In certain embodiments, the composition used in the method of treating a mood disorder or anxiety disorder further comprises at least one ingredient selected from the group consisting of L-theanine, phosphatidylcholine, α-GPC (L-α-glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, Bacopa monnieri, phosphatidylserine, pilocarpine, and cevimeline, Alara caesalpinia officinalis, Lipidium officinale, Guarana, Grapefruit multiflorum, tetrahydrocurcumin, and Solanum nigrum, and / or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, Magnolia officinalis, theanine, phosphatidylserine, Ashwagandha, Rhodiola rosea, macuna, Mesembryanthemum contortum, 5-HTP, tryptophan, saffron, vitamin D, SAMe, lion's mane, and / or huperzine A.

[0110] Further disclosed herein are methods for treating or preventing age-related cognitive decline in individuals in need thereof, comprising administering to the individual an effective amount of a composition disclosed herein. In certain embodiments, administration of the composition increases one or more of: attention, information acquisition, information processing, working memory, short-term memory, long-term memory, anterograde memory, retrograde memory, memory retrieval, discrimination learning, decision-making, inhibitory response control, attention set shifting, delayed reinforcement learning, reversal learning, temporal integration of autonomous behavior, processing speed, reasoning, problem solving, and / or social cognition. In certain embodiments, administration of the composition to the individual enhances the individual's working memory.

[0111] In certain embodiments, administering the composition to an individual enhances BDNF expression, glutathione levels, and / or dopaminergic tone, serotonergic tone, cholinergic tone, and / or reduces stress-induced Cortisol levels.

[0112] According to certain embodiments, the compositions disclosed herein are used to treat one or more medical conditions in an individual in need thereof. In certain embodiments, the disclosed compositions are administered to an individual suffering from narcolepsy, sleep apnea and shift work sleep disorder, insomnia, epilepsy, attention deficit disorder, attention deficit hyperactivity disorder (ADHD), cognitive impairment, paralysis, uncontrolled anger, migraines, substance abuse addiction, eating disorders, depression, anxiety, traumatic head injury (TBI), Parkinson's disease, Alzheimer's disease and / or dementia.

[0113] In some aspects, the disclosed compositions are neuroprotective agents. In certain embodiments, administering the disclosed compositions to an individual in need thereof is neuroprotective. In exemplary aspects of these embodiments, this neuroprotective effect is in the form of preventing dopaminergic cell death.

[0114] According to other embodiments, the disclosed compositions can be used to treat geriatric depression. In exemplary embodiments, the compositions are effective in treating individuals with geriatric depression of primary, vascular, or traumatic origin, as well as individuals with geriatric mental decline.

[0115] Administration of the disclosed compositions to an individual may include any method of providing a pharmaceutical formulation to an individual. These methods are well known to those skilled in the art and include, but are not limited to, oral administration, transdermal administration, inhalation administration, nasal administration, topical administration, intravaginal administration, ocular administration, intraaural administration, intracerebral administration, rectal administration, sublingual administration, intradermal administration, buccal administration, and parenteral administration, including injectables such as intravenous administration, intraarterial administration, intramuscular administration, and subcutaneous administration. Administration may be continuous or intermittent. In various aspects, the formulation may be administered therapeutically; that is, administered to treat an existing disease or condition. In other various aspects, the formulation may be administered prophylactically; that is, administered to prevent a disease or condition.

[0116] In another embodiment, the combination of paraxanthine and chlorogenic acid can be used at lower dosage levels and / or in combination with compounds that modulate or antagonize their activity. Such compositions can induce improved endurance performance, mood, vitality, lipolysis, energy expenditure, athletic performance, and / or decreased appetite.

[0117] An advantage of using the disclosed compositions is that the likelihood of a person developing a tolerance to the chemical composition is reduced. That is, a person may not become insensitive to the induced effects. According to certain aspects, the disclosed compositions containing a combination of paraxanthine and chlorogenic acid have at least the following significant advantages over administering a composition containing a comparable dose of caffeine. The combination of paraxanthine and chlorogenic acid has significantly lower toxicity. The combination of paraxanthine and chlorogenic acid has greater stability (e.g., does not lose potency over time to the same extent as caffeine).

[0118] Compositions containing a combination of paraxanthine and chlorogenic acid are more effective wakefulness agents (in certain embodiments, via adenosine receptor antagonism). Further, compositions containing a combination of paraxanthine and chlorogenic acid enhance striatal dopaminergic tone. Still further, the combination of paraxanthine and chlorogenic acid does not produce sleep rebound. Further, the combination of paraxanthine and chlorogenic acid does not produce withdrawal effects, as often occurs with caffeine, upon discontinuation of use. Still further, the combination of paraxanthine and chlorogenic acid does not enhance anxiety. Still further, the combination of paraxanthine and chlorogenic acid is less bitter than caffeine. Even further, the combination of paraxanthine and chlorogenic acid is effective for a larger portion of the population compared to caffeine. In another embodiment, the combination of paraxanthine and chlorogenic acid can be used at higher dose levels and / or with synergistic compounds.

[0119] Further disclosed herein are methods of improving sleep in an individual by administering a composition disclosed herein. In certain embodiments, the individual suffers from insomnia. In certain embodiments, administration of 1-methylxanthine and chlorogenic acid synergistically improves sleep in the individual relative to administration of 1-methylxanthine or chlorogenic acid alone. In other embodiments, administration of paraxanthine and chlorogenic acid synergistically improves sleep in the individual relative to administration of paraxanthine or chlorogenic acid alone.

[0120] These compositions can increase an individual's basal / resting metabolic rate, increase thermogenesis, reduce appetite, enhance cognitive performance, increase alpha wave brain activity, and / or induce euphoria. Without being bound by theory, the inventors believe that at higher dose levels, compositions containing a combination of paraxanthine and chlorogenic acid can be noradrenergic and dopaminergic and can exhibit increased adenosine receptor inhibition.

[0121] In another embodiment, the combination of paraxanthine and chlorogenic acid can be used as a topical agent for incorporation into body creams or lotions to produce a cream or lotion for brightening the skin, tightening the skin, and / or improving skin elasticity. Topical agents containing the combination of paraxanthine and chlorogenic acid can also be used to promote local transepidermal fat loss. Such a composition can also be used in a cream or lotion to promote local enhanced metabolism and / or enhanced thermogenesis.

[0122] According to other embodiments, paraxanthine and chlorogenic acid can be combined with one or more analgesics and / or anti-inflammatory agents. In an exemplary embodiment, paraxanthine and chlorogenic acid are combined with ibuprofen, salicylic acid, anti-inflammatory agents, salicin, fish oil (ω-3 fatty acids and specific small lipid-promoting resolvable derivatives), tart cherry, krill oil, astaxanthin, proteolytic enzymes, glucosamine sulfate, chondroitin sulfate, MSM (methylsulfonylmethane), SAMe (S-adenosylmethionine), ASU (avocado-soybean unsaponifiable fraction), cetyl myristoleate, falcate beans and / or triterpenes.

[0123] The dose of the combination of paraxanthine and chlorogenic acid may range from about 100 mg to about 3000 mg. In another embodiment, the range may be about 500 mg to about 2500 mg. In a further embodiment, the dose of the combination of paraxanthine and chlorogenic acid is about 600 mg. In another embodiment, the range may be at least 10% to 90% paraxanthine and 90% to 10% chlorogenic acid, respectively.

[0124] In certain embodiments, the composition comprises paraxanthine and chlorogenic acid in a ratio of about 1 :5. In certain embodiments, paraxanthine is provided in an amount of about 2 mg to about 800 mg and chlorogenic acid is provided in an amount of about 500 mg to about 2000 mg.

[0125] In an exemplary embodiment, the composition is administered at a dose of about 100 mg paraxanthine and about 500 mg chlorogenic acid.

[0126] In another embodiment, the combination of paraxanthine and chlorogenic acid is combined with one or more bioavailability enhancers. In an exemplary embodiment, bioavailability enhancers include, but are not limited to, piperine, piperine, black pepper, bergamotin, dihydroxybergamotin (CYP3A4 inhibitor), flavonoids (including hesperidin, naringin, tangeretin, quercetin, and nobiletin in isolated and combined forms), pterostilbene, fisetin, nanoencapsulation, microencapsulation, liposomes, and / or phospholipid complexes. The enhancer that is combined with the combination of paraxanthine and chlorogenic acid may depend on which properties of the combination of paraxanthine and chlorogenic acid are desired for a particular use.

[0127] In another embodiment, the combination of paraxanthine and chlorogenic acid can be administered using one or more delivery methods, including, for example, transdermal patches and / or creams, powder mixes, intravenous methods, capsules, tablets, liquids (including liquids for mixing with other beverages), soft gelatin capsules, injectable forms, and / or cosmetic applications (including soaps, lotions, and shampoos). For a variety of topical applications, the anti-inflammatory properties of the combination of paraxanthine and chlorogenic acid may be desirable.

[0128] Administration of the disclosed compositions to an individual may include any method of providing a pharmaceutical formulation to an individual. These methods are well known to those skilled in the art and include, but are not limited to, oral administration, transdermal administration, inhalation administration, nasal administration, topical administration, intravaginal administration, ocular administration, intraaural administration, intracerebral administration, rectal administration, sublingual administration, intradermal administration, buccal administration, and parenteral administration, including injectables such as intravenous administration, intraarterial administration, intramuscular administration, and subcutaneous administration. Administration may be continuous or intermittent. In various aspects, the formulation may be administered therapeutically; that is, administered to treat an existing disease or condition. In other various aspects, the formulation may be administered prophylactically; that is, administered to prevent a disease or condition.

[0129] According to certain embodiments, various aspects and embodiments of the invention are defined by the following numbered clauses:

[0130] 1. A composition comprising: about 50 mg to about 400 mg of paraxanthine and at least about 25 mg of chlorogenic acid.

[0131] 2. The composition of clause 1, wherein chlorogenic acid is present in the composition in an amount of about 25 mg to about 500 mg.

[0132] 3. The composition of clause 1, wherein paraxanthine is present in the composition in an amount of about 200 mg to about 400 mg.

[0133] 4. A composition comprising: about 50 mg to about 400 mg of 1-methylxanthine and at least about 25 mg of chlorogenic acid.

[0134] 5. A method of treating a condition in a subject in need thereof, comprising administering to the subject a composition as described in any one of clauses 1 to 4.

[0135] 6. The method of clause 5, wherein the condition is selected from narcolepsy, epilepsy, attention deficit disorder, attention deficit hyperactivity disorder (ADHD), cognitive impairment, paralysis, uncontrolled anger, migraine, substance abuse addiction, eating disorders, depression, anxiety, traumatic head injury (TBI), concussion, Parkinson's disease, Alzheimer's disease, and dementia.

[0136] 7. The method of clause 6, wherein the condition is a mood disorder.

[0137] 8. The method of clause 7, wherein the mood disorder is depression.

[0138] 9. The method of clause 8, wherein the individual has been diagnosed with or is at risk for depression.

[0139] 10. The method of clause 7, wherein the composition further comprises at least one ingredient selected from the group consisting of L-theanine, phosphatidylcholine, α-GPC (L-α-glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, Bacopa monnieri, phosphatidylserine, pilocarpine and cevimeline, Alara caesalpinia officinalis, Lipidium officinale, Guarana, Grapefruit multiflorum, tetrahydrocurcumin and Solanum nigrum and / or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, Magnolia officinalis, theanine, phosphatidylserine, Ashwagandha, Rhodiola rosea, N-acetyl-tyrosine, Mucuna pruriens, Mesembryanthemum contortum, 5-HTP, tryptophan, saffron, vitamin D, SAMe, Lion's Mane and / or Huperzine A.

[0140] 11. A method of enhancing attention in an individual in need thereof, comprising administering a composition as described in any one of clauses 1 to 4.

[0141] 12. A method of improving working memory in an individual in need thereof, comprising administering to the individual a composition comprising the composition of any one of clauses 1 to 4.

[0142] 13. A method of improving cognitive ability in an individual comprising administering the composition of any one of clauses 1 to 4.

[0143] 14. The method of clause 13, wherein the improved cognitive function is measured by an increase in one or more of: attention, information acquisition, information processing, working memory, short-term memory, long-term memory, anterograde memory, retrograde memory, memory retrieval, discrimination learning, decision-making, inhibitory response control, attentional set shifting, delayed reinforcement learning, reversal learning, temporal integration of voluntary behavior, processing speed, reasoning, problem solving, and / or social cognition.

[0144] 15. A method of preventing or treating TBI in a subject in need thereof, comprising administering the composition of any one of clauses 1 to 4.

[0145] 16. The method of clause 15, wherein administering the composition to the individual enhances expression of brain-derived neurotrophic factor (BDNF) relative to the brain of the individual to which the composition has not been administered.

[0146] 17. The method of clauses 15-16, wherein administration of the composition prevents the occurrence of TBI when administered to the individual prior to injury.

[0147] 18. A method of enhancing neuroplasticity in an individual in need thereof, comprising administering to the individual the composition of any one of clauses 1 to 4.

[0148] 19. The method of clause 18, wherein the amount of paraxanthine and / or 1-methylxanthine administered to the individual is from about 500 mg to about 400 mg, wherein the amount of chlorogenic acid administered to the individual is from about 50 mg to about 500 mg, wherein administration of paraxanthine and / or 1-methylxanthine and chlorogenic acid produces a synergistic enhancement of neuroplasticity in the individual relative to administration of paraxanthine and / or 1-methylxanthine or chlorogenic acid alone.

[0149] 20. A method of improving digestive health in a subject in need thereof, comprising administering to the subject a composition according to any one of clauses 1 to 4.

[0150] 21. The method of clause 20, wherein digestive health is improved by enhancing the individual's microbiome.

[0151] 22. The method of clause 21, wherein the amount of paraxanthine administered to the individual is from about 500 mg to about 400 mg, wherein the amount of chlorogenic acid administered to the individual is from about 50 mg to about 500 mg, wherein administration of paraxanthine and chlorogenic acid results in a synergistic improvement in the digestive health of the individual relative to administration of paraxanthine or chlorogenic acid alone.

[0152] 23. A method of reducing hypertension in a subject in need thereof, comprising administering to the subject the composition of any one of clauses 1 to 4.

[0153] 24. The method of clause 23, wherein the amount of paraxanthine administered to the individual is about 500 mg to about 400 mg, wherein the amount of chlorogenic acid administered to the individual is about 50 mg to about 500 mg, wherein administration of paraxanthine and chlorogenic acid produces a synergistic reduction in hypertension in the individual relative to administration of paraxanthine or chlorogenic acid alone.

[0154] 25. A method of enhancing energy or mood in an individual, comprising administering to the individual a composition comprising effective amounts of paraxanthine and chlorogenic acid, wherein the amount of paraxanthine administered to the individual is from about 500 mg to about 400 mg, wherein the amount of chlorogenic acid administered to the individual is from about 50 mg to about 500 mg, wherein administration of paraxanthine and chlorogenic acid produces a synergistic enhancement of energy and / or mood in the individual relative to administration of either paraxanthine or chlorogenic acid alone.

[0155] 26. A method of regulating cellular energy homeostasis comprising administering to a subject a composition according to any one of clauses 1 to 4.

[0156] 27. The method of clause 26, wherein administering the composition inhibits 5' AMP-activated protein kinase and / or CD38 in the individual.

[0157] 28. The method of clause 26, wherein administration of the composition increases NAD levels in the individual.

[0158] 29. The method of clause 26, wherein administration of the composition alleviates the individual's cellular energy deficit state.

[0159] 30. The method of any one of clauses 26 to 29, wherein the amount of paraxanthine administered to the individual is about 500 mg to about 400 mg, wherein the amount of chlorogenic acid administered to the individual is about 50 mg to about 500 mg, wherein administration of paraxanthine and chlorogenic acid produces a synergistic regulation of cellular energy homeostasis in the individual relative to administration of paraxanthine or chlorogenic acid alone.

[0160] 31. A method of regulating blood glucose levels in a subject comprising administering to the subject a composition according to any one of clauses 1 to 4.

[0161] 32. The method of clause 31, wherein administering the composition to the individual reduces advanced glycation end products in the individual.

[0162] 33. The method of clause 31, wherein administering the composition to the subject reduces glycation in the subject.

[0163] 34. The method of any preceding clause, further comprising administering to the individual a composition comprising a metabolite of paraxanthine and / or chlorogenic acid.

[0164] 35. The method of any preceding clause, wherein the composition administered to the individual is substantially free of caffeine.

[0165] 36. A composition comprising: about 50 mg to about 400 mg of paraxanthine or 1-methylxanthine and at least about 25 mg of chlorogenic acid.

[0166] 37. The composition of clause 36, wherein chlorogenic acid is present in the composition in an amount of about 25 mg to about 500 mg.

[0167] 38. The composition of clause 36, wherein the composition comprises paraxanthine in an amount of about 200 mg to about 400 mg.

[0168] 39. The composition of clause 36, wherein the composition comprises 1-methylxanthine in an amount of about 200 mg to about 400 mg.

[0169] 40. A method of improving cognition in an individual comprising administering a composition comprising: about 50 mg to about 400 mg of paraxanthine or 1-methylxanthine and at least about 25 mg of chlorogenic acid.

[0170] 41. The method of clause 40, wherein chlorogenic acid is present in the composition in an amount of about 25 mg to about 500 mg.

[0171] 42. The method of clause 40, wherein the composition comprises paraxanthine in an amount of about 200 mg to about 400 mg.

[0172] 43. The method of clause 42, wherein administration of paraxanthine and chlorogenic acid produces a synergistic enhancement in cognitive function in the individual relative to administration of paraxanthine or chlorogenic acid alone.

[0173] 44. The method of clause 40, wherein the composition comprises 1-methylxanthine in an amount of about 200 mg to about 400 mg.

[0174] 45. The method of clause 44, wherein administration of 1-methylxanthine and chlorogenic acid produces a synergistic enhancement in cognitive function in the individual relative to administration of 1-methylxanthine or chlorogenic acid alone.

[0175] 46. The method of clause 40, wherein the improved cognitive ability is measured by an increase in one or more of: attention, information acquisition, information processing, working memory, short-term memory, long-term memory, anterograde memory, retrograde memory, memory retrieval, discrimination learning, decision-making, inhibitory response control, attentional set shifting, delayed reinforcement learning, reversal learning, temporal integration of voluntary behavior, processing speed, reasoning, problem solving, and / or social cognition.

[0176] 47. The method of clause 46, wherein the improved cognitive ability is measured by improved working memory.

[0177] 48. The method of clause 40, wherein administration of the composition to the individual enhances BDNF expression, glutathione levels and / or dopaminergic tone, serotonergic tone, cholinergic tone, and / or reduces stress-induced Cortisol levels.

[0178] 49. A method of improving sleep in a subject comprising administering a composition comprising: about 50 mg to about 400 mg of paraxanthine or 1-methylxanthine and at least about 25 mg of chlorogenic acid.

[0179] 50. The method of clause 49, wherein chlorogenic acid is present in the composition in an amount of about 25 mg to about 500 mg.

[0180] 51. The method of clause 49, wherein the composition comprises paraxanthine in an amount of about 200 mg to about 400 mg.

[0181] 52. The method of clause 51, wherein administration of paraxanthine and chlorogenic acid produces a synergistic improvement in sleep in the individual relative to administration of paraxanthine or chlorogenic acid alone.

[0182] 53. The method of clause 49, wherein the composition comprises 1-methylxanthine in an amount of about 200 mg to about 400 mg.

[0183] 54. The method of clause 53, wherein administration of 1-methylxanthine and chlorogenic acid produces a synergistic improvement in sleep in the individual relative to administration of 1-methylxanthine or chlorogenic acid alone.

[0184] 55. The method of clause 49, wherein the individual suffers from insomnia.

[0185] Example

[0186] The following examples are put forward so as to provide those of ordinary skill in the art with a complete disclosure and description of how to prepare and evaluate certain embodiments of the compounds, compositions, articles, devices and / or methods claimed herein, and are intended to be purely exemplary of the present invention and are not intended to limit the scope of what the inventors regard as their invention. However, those skilled in the art will appreciate that, in light of the present disclosure, many changes can be made to the specific embodiments disclosed and still obtain similar or similar results without departing from the spirit and scope of the invention.

[0187] Example 1 - Various Embodiments for Assessing Pentobarbital-Induced Sleep

[0188] Although a number of embodiments are disclosed, other embodiments of the present disclosure will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the disclosed compositions, systems, and methods. As will be appreciated, the disclosed compositions, systems, and methods are capable of modification in various obvious respects, all without departing from the spirit and scope of the present disclosure. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive.

[0189] This example was conducted to evaluate the efficacy of the test substance on sodium pentobarbital-induced sleep activity in experimental mice. Table 1 below shows information about the mice.

[0190] Table 1. Mouse information

[0191]

[0192] Mice were randomly divided into nine groups, each containing eight mice. These groups were a normal control group, which did not receive any dose of sodium pentobarbital or any other test substance; a pathological control group, which received any dose of sodium pentobarbital and scopolamine; a PX group, which received any dose of sodium pentobarbital and paraxanthine; a CA group, which received any dose of sodium pentobarbital and chlorogenic acid; a 1-MX group, which received any dose of sodium pentobarbital and 1-methylxanthine; a PX+CA group, which received any dose of sodium pentobarbital, paraxanthine, and chlorogenic acid; and a 1-MX+CA group, which received any dose of sodium pentobarbital, 1-methylxanthine, and chlorogenic acid. Dosage information can be found in Table 2 below.

[0193] On the same day of the experiment, mice of different groups were treated with control and test substance respectively. After 30 minutes, except the normal control group, sodium pentobarbital of 40 mg / kg body weight dosage was used to induce sleep to all mice groups. The administration of test substance was carried out by intraperitoneal injection. The sleep onset time of all mice was recorded. After inducing sleep, mice were placed in an inverted position, and when sedation was finished, the time point at which mice recovered to normal posture was recorded. The time interval between administration and the start of sleep was recorded as latency. Table 2 shows the data recorded from the embodiment.

[0194] Table 2. Effects on pentobarbital-induced sleep.

[0195]

[0196] Example 2 - Evaluation of various embodiments of cognitive enhancement effects based on the Plus-Maze Model

[0197] This example is used to evaluate the effects of the test substance on the behavioral activity / memory enhancement activity of experimental rats. Table 3 gives the information of the rats selected for this example.

[0198] Table 3. Rat information

[0199]

[0200] Rats were randomly divided into nine groups, each containing eight rats. These groups included a normal control group, which did not receive any test substance at various doses; a pathological control group, which received only scopolamine at various doses; a PX group, which received scopolamine and paraxanthine at various doses; a CA group, which received scopolamine and chlorogenic acid at various doses; a 1-MX group, which received scopolamine and 1-methylxanthine at various doses; a PX+CA group, which received scopolamine, paraxanthine, and chlorogenic acid at various doses; and a 1-MX+CA group, which received scopolamine, 1-methylxanthine, and chlorogenic acid at various doses. The rats were treated with the test substances daily for ten consecutive days.

[0201] During the 10-day test, the test substance was orally administered 30 minutes prior to the injection of 1 mg / kg body weight of scopolamine to induce amnesia in all groups of rats, except the control group. Scopolamine injections were administered intraperitoneally. This was followed by behavioral testing using an elevated plus maze apparatus to measure long-term memory-enhancing activity. Table 4 shows the data recorded in the Examples.

[0202] Table 4. Effects on cognitive enhancement - elevated plus maze.

[0203]

[0204] Several brain biomarkers were also measured in rats. Tables 5 and 6 show these data.

[0205] Table 5. Brain biomarker concentrations and cognitive improvement.

[0206]

[0207] Table 6. Brain biomarker concentrations and cognitive improvement.

[0208]

[0209] Example 3 - Evaluation of various embodiments of Morris water maze-based cognitive enhancement effects

[0210] This example is used to evaluate the effects of the test substance on the behavioral activity / memory enhancement activity of experimental rats. Table 7 gives the information of the rats selected for this example.

[0211] Table 7. Rat information

[0212]

[0213] Rats were randomly divided into nine groups, each containing eight rats. These groups included a normal control group, which did not receive any test substance at various doses; a pathological control group, which received only scopolamine at various doses; a PX group, which received scopolamine and paraxanthine at various doses; a CA group, which received scopolamine and chlorogenic acid at various doses; a 1-MX group, which received scopolamine and 1-methylxanthine at various doses; a PX+CA group, which received scopolamine, paraxanthine, and chlorogenic acid at various doses; and a 1-MX+CA group, which received scopolamine, 1-methylxanthine, and chlorogenic acid at various doses. The rats were treated with the test substances daily for ten consecutive days.

[0214] During the 10-day test, the test substance was orally administered 30 minutes prior to the injection of 1 mg / kg body weight of scopolamine to induce amnesia in all groups of rats, except the control group. Scopolamine injections were administered via intraperitoneal injection. Subsequently, behavioral testing was performed using the Morris water maze apparatus to measure long-term memory enhancement activity. Table 8 shows the data recorded in the Examples.

[0215] Table 8. Effects on cognitive enhancement – Morris water maze.

[0216]

[0217] Several brain biomarkers were also measured in rats. Tables 9 and 10 show these data.

[0218] Table 9. Brain biomarker concentrations and cognitive improvement.

[0219]

[0220] Table 10. Brain biomarker concentrations and cognitive improvement.

[0221]

Claims

1. A composition comprising: about 50 mg to about 400 mg of paraxanthine or 1-methylxanthine and at least about 25 mg of chlorogenic acid.

2. The composition according to claim 1, wherein Chlorogenic acid is present in the composition in an amount of about 25 mg to about 500 mg.

3. The composition according to claim 1, wherein The composition comprises paraxanthine in an amount of about 200 mg to about 400 mg.

4. The composition according to claim 1, wherein The composition comprises 1-methylxanthine in an amount of about 200 mg to about 400 mg.

5. A method of improving cognition in an individual comprising administering a composition comprising: about 50 mg to about 400 mg of paraxanthine or 1-methylxanthine and at least about 25 mg of chlorogenic acid.

6. The method according to claim 5, characterized in that Chlorogenic acid is present in the composition in an amount of about 25 mg to about 500 mg.

7. The method according to claim 5, wherein The composition comprises paraxanthine in an amount of about 200 mg to about 400 mg.

8. The method according to claim 7, characterized in that Administration of paraxanthine and chlorogenic acid produces a synergistic enhancement in cognitive function in the individual relative to administration of either paraxanthine or chlorogenic acid alone.

9. The method according to claim 5, wherein The composition comprises 1-methylxanthine in an amount of about 200 mg to about 400 mg.

10. The method according to claim 9, characterized in that Administration of 1-methylxanthine and chlorogenic acid produces a synergistic enhancement in cognitive function in the individual relative to administration of 1-methylxanthine or chlorogenic acid alone.

11. The method according to claim 5, characterized in that Improved cognitive abilities are measured by increases in one or more of the following: attention, information acquisition, information processing, working memory, short-term memory, long-term memory, anterograde memory, retrograde memory, memory retrieval, discrimination learning, decision-making, inhibitory response control, attentional set shifting, delayed reinforcement learning, reversal learning, temporal integration of voluntary actions, processing speed, reasoning, problem solving, and / or social cognition.

12. The method according to claim 11, characterized in that Improved cognitive performance was measured by improved working memory.

13. The method according to claim 5, characterized in that Administration of the composition to the individual enhances BDNF expression, glutathione levels, and / or dopaminergic tone, serotonergic tone, cholinergic tone, and / or reduces stress-induced Cortisol levels.

14. A method of improving sleep in an individual comprising administering a composition comprising: about 50 mg to about 400 mg of paraxanthine or 1-methylxanthine and at least about 25 mg of chlorogenic acid.

15. The method according to claim 14, wherein Chlorogenic acid is present in the composition in an amount of about 25 mg to about 500 mg.

16. The method according to claim 14, wherein The composition comprises paraxanthine in an amount of about 200 mg to about 400 mg.

17. The method according to claim 16, characterized in that Administration of paraxanthine and chlorogenic acid produces a synergistic improvement in sleep in the subject relative to administration of paraxanthine or chlorogenic acid alone.

18. The method according to claim 14, wherein The composition comprises 1-methylxanthine in an amount of about 200 mg to about 400 mg.

19. The method according to claim 18, characterized in that Administration of 1-methylxanthine and chlorogenic acid produces a synergistic improvement in sleep in the subject relative to administration of 1-methylxanthine or chlorogenic acid alone.

20. The method according to claim 14, wherein The individual suffers from insomnia.

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