CN118632697A - Bioactive compositions and methods of use thereof - Google Patents

Abstract

The disclosed compositions, systems and methods relate to dietary supplements for human consumption and include a combination of paraxanthine and tyrosine and/or taurine and optionally other compounds that modulate the effects of the combination of paraxanthine and tyrosine and/or taurine. Further disclosed are methods of using the aforementioned compositions for improving at least one of endurance performance, mood, vitality, lipolysis, energy expenditure, athletic performance and/or decreased appetite.

Description

Bioactive compositions and methods of use thereof

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 63/203,644, filed on July 27, 2021, and entitled “COMBINATION OF PARAXANTHINE AND TYROSINE-BASED BIOACTIVE COMPOSITION AND METHOD OF USE THEREOF,” and U.S. Provisional Application No. 63/226,057, filed on July 27, 2021, and entitled “COMBINATION OF PARAXANTHINE AND TAURINE-BASED BIOACTIVE COMPOSITION AND METHOD OF USE THEREOF,” each of which is hereby incorporated by reference in its entirety.

Technical Field

The disclosed technology generally relates to compositions and methods for enhancing muscle and/or cognitive function by administering a composition containing a combination of paraxanthine, tyrosine and/or taurine.

Background Art

Caffeine is a bitter, white, crystalline purine, a methylxanthine alkaloid, and is chemically related to the adenine and guanine bases of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). It is found in the seeds, nuts, or leaves of several plants native to Africa, East Asia, and South America, and helps protect them from predatory insects and prevents nearby seeds from germinating. The best-known source of caffeine is the coffee bean, a misnomer for the seed of the coffee plant.

The caffeine concentration in coffee beverages can be quite variable. A standard cup of coffee is often assumed to provide 100mg caffeine, but a recent analysis of 14 different specialty coffees purchased in American coffee shops found that the caffeine amount in 8oz (～240ml) brewed coffee ranges from 72-130mg (McCusker, R.R., Goldberger, B.A. and Cone, E.J.2003.Caffeine content of specialty coffees.J.Anal.Toxicol., 27:520-522.). The caffeine in espresso ranges from 58-76mg in a single serving. Interestingly, the caffeine content of the same type of coffee purchased from the same store on separate six days ranges from 130 to 282mg per 8-oz portion. Many individuals experience sleep, anxiety and/or nervous problems due to caffeine, which can be aggravated by unexpectedly high doses.

Therefore, there is a need in the art to identify alternative chemical compounds and mixtures thereof that can provide benefits. It is also desirable to provide such chemical compounds and mixtures thereof that can be used to provide various benefits as a function of concentration, thus requiring less material to produce.

Summary of the invention

Disclosed herein are compositions comprising paraxanthine and tyrosine and/or taurine and methods of use thereof. In certain aspects, paraxanthine and tyrosine are present in a ratio of about 1:4 to about 1:30.

In certain embodiments, the disclosed compositions comprise a further 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, lauroyl polyethylene glycol, a co-crystal of lauroyl polyethylene glycol derivatives, bioperine. Products, piperine, black pepper, bergamot, dihydroxybergamot (CYP3A4), flavonoids (naringin, hesperidin, nobiletin, tangeretin, quercetin), pterostilbene, fisetin, phytosomes, salicin, fish oil (ω-3 fatty acids and specific small lipid pro-inflammatory epoxide derivatives), oxylipids, tart cherry, krill oil, astaxanthin, protease, glucosamine sulfate, chondroitin sulfate, MSM (methylsulfonylmethane), SAMe (S-adenosylmethionine), ASU (avocado soy unsaponifiable fraction), cetyl myristate, Dolichos falcata), triterpenes, catechins, Andrographis paniculata, Scutalleria baicalensis, Agmatine sulfate, Stinging Nettle, Sea Buckthorn, Curcumin, Cissus Quadrilangularis, Boswellia Serrata, Wasabia japonica (mustard extract for tea tree oil), Emu Oil, Arnica, Mangifera indica L. (Anacardiaceae), Lagenaria breviflora, Zingiber officinale, officinale (ginger and gingerols/shogaols), hoodia gordonii, caffeine, yohimbine, methyl synephrine, synephrine, theobromine, flavonoids, tocopherols, theophylline, alpha-yohimbine, conjugated linoleic acid (CLA), octopamine, evodiamine, passion flower, red pepper, cayenne pepper, raspberry ketones, guggul, green tea, guarana, kola nut, beta-phenylethylamine, Acacia rigidula, forskolin (Coleus forskohlli), theophylline, synephrine, yohimbe, rhodiola rosea, ashwagandha, ginseng, ginkgo, Siberian ginseng, astragalus, licorice, green tea, ganoderma, dehydroepiandrosterone (DHEA), pregnenolone, N-acetyltyrosine, glucuronolactone, acetyl-L-carnitine, 5-hydroxytryptophan, tryptophan, phenylethylamine, Sceletium tortuosum (and mesembrine alkaloids), Dendrobium sp., Acacia, PQQ (pyrroloquinoline quinone), ubiquinone (01), nicotinamide riboside, picamiron, huperzine A (Chinese clubmoss or Huperzia serrata), L-dopa, Mucuna pruriens pruriens and forskolin (Coleus forskohlii), 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, ornithine, citrulline, pyruvate, Eleutherococcus senticosus, D-ribose, whey protein, trimethylglycine, arginine, HMB (beta-hydroxy beta-methylbutyrate), milk protein, Schisandra chinensis, leucine, betalains, leucine, L-carnitine, sodium bicarbonate, arachidonic acid, beta-alanine, rape steroids, alanyl-glutamine, Rhaponticum carthamoides, casein, ecdysteroids, creatine, branched-chain amino acids, beetroot, coffee, nitrates, Panax ginseng, clenbuterol, alpha-GPC, valine, colostrum, Trichopus cerevisiae zeylanicus), ashwagandha, Terminalia arjuna, egg, ursolic acid, isoleucine, medium chain triglycerides, glutamine, zinc, vitamin D, maca, Schizandra, nicotinamide mononucleotide (NMN), exogenous ketones, ergothioneine, berberine, dihydroberberine, and combinations thereof.

In certain embodiments, compositions comprises the combination of paraxanthine and tyrosine homologue, or the combination of paraxanthine and tyrosine analogue.In exemplary implementation, tyrosine homologue or analogue are N-acetyl-L-tyrosine, glycyl-L-tyrosine, N-acetyl-L-tyrosine ethyl ester or N-acetyl-L-tyrosine methyl ester.In further implementation, tyrosine exists with polymeric form, and wherein polymeric form is dityrosine (Tyr-Tyr), trityrosine (Tyr-Tyr-Tyr), tetratyrosine (Tyr-Tyr-Tyr-Tyr) or contains aforementioned peptide.In further implementation, tyrosine exists as lysyltyrosine or leucine-tyrosine.In even further implementation, tyrosine is present in the dipeptide with structure L-Tyr-X, wherein X is amino acid.

Further disclosed herein is a method for the motor performance or energy in an object by administering a composition comprising an effective amount of paraxanthine and tyrosine to an object. In certain embodiments, relative to the administration of independent paraxanthine or taurine, the administration of paraxanthine and taurine produces a synergistic increase in motor performance or energy in an object. In certain implementations, paraxanthine is provided in an amount of about 25mg to about 400mg, and wherein tyrosine is provided in an amount of 100-150mg/kg of the body weight of the object. According to certain embodiments, the object experiences increased endurance or increased strength.

In certain implementations, the ratio of the amounts of paraxanthine and tyrosine administered to the subject is about 1:10 to about 1:30. In further implementations, the ratio of the amounts of paraxanthine and tyrosine administered to the subject is about 1:10 to about 1:10.

In a further embodiment, the composition is substantially free of caffeine.

Further disclosed herein is a method for improving cognitive function in an object, comprising administering to an object a composition comprising an effective amount of paraxanthine and tyrosine. In certain embodiments, the cognitive function improved in the object is measured by one or more of the following increases: attention, information acquisition, information processing, working memory, short-term memory, long-term memory, anterograde memory, retrograde memory, memory retrieval, discrimination learning, decision making, inhibition of response control, attention set shift, delayed reinforcement learning, reversal learning, time integration of voluntary behavior, processing speed, reasoning, problem solving and/or social cognition. In certain embodiments, administering compositions to an object enhances the mood in the object. In a further embodiment, relative to the administration of independent paraxanthine or tyrosine, the administration of paraxanthine and tyrosine produces a synergistic enhancement of cognitive function in an object.

Further disclosed herein are methods of enhancing energy or mood in a subject, comprising administering to the subject a composition comprising effective amounts of paraxanthine and taurine, wherein the amount of paraxanthine administered to the subject is from about 25 mg to about 800 mg, and wherein the amount of taurine administered to the subject is from about 100 mg to about 6000 mg, and wherein administration of paraxanthine and taurine produces a synergistic enhancement of energy and/or mood in the subject relative to administration of either paraxanthine or taurine alone.

Although multiple 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 can have modifications in various obvious aspects, all without departing from the spirit and scope of the present disclosure. Accordingly, the drawings and detailed description are to be regarded as illustrative and non-restrictive in nature.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 shows exemplary data demonstrating the effects of certain disclosed compositions on forelimb strength in mice.

DETAILED DESCRIPTION

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 the construction and the arrangement of parts set forth in the following description or shown in the accompanying drawings. The present invention can have other embodiments and can be practiced and carried out in various ways. In addition, it should be understood that the wording and terminology used herein are for descriptive purposes and should not be considered as limiting.

Ranges can be expressed herein as from "about" a particular value and/or to "about" another particular value. When such ranges are expressed, a further aspect includes from a particular value and/or to another particular value. Similarly, when a value is expressed as an approximation using the antecedent "about", it is understood that the particular value constitutes a further aspect. It should be further understood that the respective endpoints of the range are significant with respect to the other endpoint and independently of the other endpoint. It should also be understood that multiple values are disclosed herein, and in addition to the value itself, each value is also disclosed herein as "about" the particular value. For example, if the value "10" is disclosed, "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, 11, 12, 13 and 14 are also disclosed.

As used herein, the term "subject" refers to the target of administration, such as an animal. Therefore, the subject of the method disclosed herein can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cattle, cat, guinea pig or rodent. The term does not indicate a specific age or gender. Therefore, it is expected to cover adult and newborn subjects, whether male or female, and fetuses. In one aspect, the subject is a mammal. The patient refers to an object suffering from a disease or condition. As used herein, the term "treatment" refers to the medical management of the patient, which is intended to cure, improve, stabilize or prevent a disease, pathological condition or condition. The term includes active treatment, i.e., treatment specifically for the improvement of a disease, pathological condition or condition, and also includes etiological treatment, i.e., treatment for the removal of the cause of the relevant disease, pathological condition or condition. In addition, the term also includes palliative treatment, i.e., treatment designed to relieve symptoms rather than cure a disease, pathological condition or condition; preventive treatment, i.e., treatment intended to minimize or partially or completely inhibit the development of a relevant disease, pathological condition or condition; and supportive treatment, i.e., treatment for supplementing another specific therapy, which is directed to the improvement of a relevant disease, pathological condition or condition. In various aspects, the term encompasses any treatment of a subject, including a mammal (e.g., a human), and includes: (i) preventing a disease from occurring in a subject that may be susceptible to the disease but has not yet been diagnosed as having it; (ii) inhibiting the disease, i.e., arresting its development; or (iii) ameliorating the disease, i.e., causing regression of the disease. In one aspect, the subject is a mammal, such as a primate, and in a further aspect, the subject is a human.

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

As used herein, the terms "effective amount" and "effective amount" refer to an amount sufficient to achieve the desired result or to have an effect on an undesirable condition. For example, a "therapeutically effective amount" refers to an amount sufficient to achieve the desired therapeutic result or to have an effect on an undesirable symptom, but generally not sufficient to cause unacceptable adverse side effects. The specific therapeutically effective dosage level for any particular patient will depend on various factors, including the condition to be treated and the severity of the condition; 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; the drugs used in combination or simultaneously with the specific compound employed, and similar factors well known in the medical field. 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 necessary, the effective daily dose can be divided into multiple doses for the purpose of administration. Thus, a single dose composition may contain such an amount or a submultiple thereof constituting the daily dose. In the case of any contraindications, the dose may be adjusted by the individual physician. The dose may vary and may be administered in one or more doses per day for one or several days. Guidance can be found in the literature as to appropriate dosages for a given class of drug products.In further various aspects, the formulations may be administered in a "prophylactically effective amount"; that is, an amount effective to prevent a disease or condition.

As used herein, the term "synergistic effect" or grammatical variations thereof means and includes the cooperative 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 activities of each active compound alone.

As used herein, the term "synergistically effective amount" means and includes an amount of two or more active compounds that provides a synergistic effect as defined above.

As used herein, the term "substantially" refers to the complete or almost complete scope or degree of an action, characteristic, property, state, structure, project or result. For example, an object that is "substantially" closed means that the object is completely closed or almost completely closed. In some cases, the exact allowable deviation degree from absolute completeness may depend on the specific context. However, in general, it will be close to completely so as to have an overall result that is absolutely and completely identical with obtaining. When used in a negative sense, the use of "substantially" is equally applicable to refer to the complete or almost complete lack of an action, characteristic, property, state, structure, project or result. For example, a composition that is substantially free of particles will completely lack particles, or almost completely lack particles so that the effect will be the same as it completely lacks particles. In other words, a composition that is substantially free of ingredients or elements may actually still contain such items, as long as there is no measurable effect thereof.

As used herein, "cognitive function" refers to any higher-order intellectual brain process or brain state involved in learning and/or memory, respectively, 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 voluntary actions, and expressing interest in the surrounding environment and self-care, processing speed, reasoning, and problem solving and social cognition.

Composition

Compositions comprising a combination of paraxanthine and tyrosine and their associated uses are disclosed. Compositions comprising a combination of paraxanthine and taurine and their associated uses are further disclosed herein. Paraxanthine can be produced synthetically, or can be isolated from a natural source or by fermentation. Paraxanthine isolated from such sources can be purified to a purity of 95% or more. Optionally, less purification can be used so that the combination of paraxanthines accounts for 50% or even less of the material. In some embodiments, it may be preferred to utilize paraxanthine isolated from a natural source, which may include other homologues of paraxanthine commonly found in the paraxanthine source.

In certain embodiments, the composition is formulated so that the dose contains paraxanthine in the range of 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).

The chemical formula of tyrosine is C ₉ H ₁₁ NO ₃ and has a molecular weight of 181.19. Tyrosine is a dietary amino acid. It is also synthesized by the body from phenylalanine or phenylethylamine. In addition to its value as an energy substrate and in protein synthesis, it is also a precursor for numerous biogenic amines and neurotransmitters. Tyrosine crosses the blood-brain barrier and enters neurons where it becomes metabolized into catecholamine neurotransmitters. In certain embodiments, the source of tyrosine is a natural source. In further embodiments, the source of tyrosine is synthetic. In still further embodiments, tyrosine is produced by fermentation.

According to further embodiments, tyrosine exists as an ester (e.g., L-tyrosine ethyl ester, L-tyrosine methyl ester). In further embodiments, tyrosine is provided by tyrosine derivatives (e.g., N-acetyl-L-tyrosine and/or glycyl-L-tyrosine). In further embodiments, tyrosine derivatives exist as esters (e.g., N-acetyl-L-tyrosine ethyl ester and N-acetyl-L-tyrosine methyl ester). In further embodiments, tyrosine exists in a polymeric form. Examples include, but are not limited to, dityrosine (Tyr-Tyr), trityrosine (Tyr-Tyr-Tyr), tetratyrosine (Tyr-Tyr-Tyr-Tyr) or peptides containing the foregoing.

According to further embodiments, tyrosine is present in a dipeptide having the structure L-Tyr-X, wherein X is an amino acid. In an exemplary implementation, tyrosine is present in the form of lysyltyrosine or leucine-tyrosine.

The chemical formula of taurine is C ₂ H ₇ NO ₃ S, and has a molecular weight of 125.14. Taurine is naturally derived from cysteine. Mammal taurine synthesis occurs in the pancreas via the cysteine sulfinic acid pathway. In this pathway, cysteine is first oxidized to its sulfinic acid by cysteine dioxygenase catalysis. Cysteine sulfinic acid is in turn decarboxylated by cysteine sulfinic acid decarboxylase to form hypotaurine. Hypotaurine is enzymatically oxidized by hypotaurine dehydrogenase to produce taurine. Synthetic taurine is obtained by the aminolysis of isethionic acid (2-hydroxyethanesulfonic acid), which in turn is obtained by the reaction of ethylene oxide with aqueous sodium bisulfite. The direct method involves the reaction of aziridine with sulfurous acid. Taurine is essential for cardiovascular function and the development and function of skeletal muscle, retina and central nervous system. In certain embodiments, the source of taurine is a natural source. In a further embodiment, the source of taurine is synthetic.In an even further embodiment, taurine is produced by fermentation.

In certain embodiments, taurine is present in an amount ranging from about 500 mg to about 6000 mg (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 5,500 mg, or about 6000 mg, etc., or any range or value therein).

In certain embodiments, the combination of paraxanthine and tyrosine and/or taurine can be combined with one or more other chemical compounds (e.g., other active ingredients) to provide a variety of positive effects in a subject. By changing the combination of paraxanthine and tyrosine and/or the dosage of the chemical compound with which it is combined, a variety of physiological effects can be selected. The composition may primarily provide a single benefit, or may provide multiple benefits simultaneously. In certain embodiments, the combination of paraxanthine and tyrosine 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, co-crystallization products of piperine. , piperine, black pepper, bergamot, dihydroxybergamot (CYP3A4), flavonoids (naringin, hesperidin, nobiletin, tangeretin, quercetin), pterostilbene, fisetin, phospholipid complex, salicin, fish oil (ω-3 fatty acids and specific small lipid pro-inflammatory epoxide derivatives), oxylipids, tart cherry, krill oil, astaxanthin, protease, glucosamine sulfate, chondroitin sulfate, MSM (methylsulfonylmethane), SAMe (S-adenosylmethionine), ASU (avocado soy unsaponifiable fraction), cetyl myristate, lentil, triterpenoids, catechu, andrographis paniculata, scutellaria baicalensis, agmatine sulfate , stinging nettle, sea buckthorn, curcumin, quislin, frankincense, horseradish (mustard extract for tea tree oil), emu oil, arnica, mango (Anacardiaceae), calendula, ginger (ginger and gingerols/shogaols), prickly pear, caffeine, yohimbine, methyl synephrine, synephrine, theobromine, tocopherol, theophylline, alpha-yohimbine, conjugated linoleic acid (CLA), octopamine, evodiamine, passion flower, red pepper, cayenne pepper, raspberry ketone, Indian myrrh, green tea, guarana, kola nut, beta-phenylethylamine, acacia, forskolin (Coleus forskohlii), theophylline, synephrine, yohimbine, rhodiola rosea, ashwagandha, ginseng, ginkgo, sibiricum Panax ginseng, Astragalus, Licorice, Green tea, Ganoderma lucidum, Dehydroepiandrosterone (DHEA), Pregnenolone, N-acetyltyrosine, Glucuronolactone, Acetyl-L-carnitine, 5-HTP, Tryptophan, Phenylethylamine, Mesembryanthemum contortum (and Mesembrine alkaloids), Dendrobium species, Acacia, PQQ (pyrroloquinoline quinone), Ubiquinone (01), Nicotinamide riboside, Picamiron, Huperzine A (Chinese club moss or Huperzia serrata), L-DOPA, Mucuna pruriens, Forskolin (Coleus forskohlii), 2-(Dimethylamino)ethanol (DMAE), DMAE bitartrate, Medium chain triglycerides, Creatine, Citrulline, Arginine, Hericium erinaceus (lions mane), Cordyceps sinensis, Leucine, Isoleucine, Valine, BAIBA, Ergothioneine, Capsicum annuum, Kanna, Huperzine A, Huperzine A, Maca, Ginseng, Ashwagandha, Rhodiola rosea, Theanine, and combinations thereof.

In certain embodiments, paraxanthine and tyrosine are present in approximately equal amounts. In these embodiments, on the basis of w/v, paraxanthine and tyrosine each constitute approximately 50% of the combined weight of paraxanthine and tyrosine in the composition. In certain further embodiments, the range may be at least 10% to 90% paraxanthine and 90% to 10% tyrosine, respectively.

In further embodiments, paraxanthine and tyrosine are present in a ratio of 1 :4 to about 1 :30. In still further embodiments, paraxanthine and tyrosine are present in a ratio of about 1 :4 to about 1 :10.

In certain embodiments, tyrosine is administered to a subject at a dosage ranging from about 100-150 mg/kg of the subject's body weight.

In certain embodiments, paraxanthine and taurine are present in approximately equal amounts. In these embodiments, on a w/v basis, paraxanthine and taurine each constitute approximately 50% of the combined weight of paraxanthine and taurine in the composition. In certain further embodiments, the range may be at least 10% to 90% paraxanthine and from 90% to 10% taurine, respectively. In further embodiments, taurine and paraxanthine are present in a ratio of about 4:1 to about 1:4.

In certain embodiments, the composition is formulated so that the dose contains paraxanthine in the range of 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).

In certain embodiments, the composition is formulated so that a dose contains tyrosine in the range of about 500 to about 13,500 mg (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).

Depending on object to be treated and route of administration, the compound of the present invention can be administered in different doses. Although dosage varies from object to object, suitable daily dose is in the range of about 1 to about 1000mg (for example, about 1mg, about 5mg, about 10mg, about 15mg, about 20mg, about 25mg, about 30mg, about 35mg, about 40mg, about 45mg, about 50mg, about 75mg, 100, about 150mg, about 200mg, about 250mg, about 300mg, about 350mg, about 400mg, about 450mg, about 500mg, about 550mg, about 600mg, about 650mg, about 700mg, about 750mg, about 800mg, about 850mg, about 900mg, about 950mg or about 1000mg etc., or any scope or value therein)/object administered with single dose or multiple dose.

In certain embodiments, the compositions are formulated so that the doses contain about 1 to about 1000 mg each (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 , about 850 mg, about 900 mg, about 950 mg or about 1000 mg, etc., or any range or value therein) of paraxanthine, and tyrosine ranging from 400 to about 3000 mg (e.g., 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, about 1000 mg, about 1500 mg, about 2000 mg, about 2500 mg, or about 3000 mg, etc., or any range or value therein).

Nutritional Supplements

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

Nutritional supplements can come in a variety of forms, such as tablets, capsules, softgels, gelcaps, liquids, or powders. Some dietary supplements can help ensure adequate dietary intake of essential nutrients; others may help reduce the risk of disease.

Food Products

The composition of the present disclosure can take the form of food products. Herein, the term "food" is used in a broad sense, and covers food and beverages for people and food and beverages (i.e. feed) for animals. Preferably, the food product is suitable for and designed for human consumption.

The food may be in the form of a liquid, a solid or a suspension, depending on the use and/or the mode of application and/or the mode of administration.

When in the form of a food product, the composition may include 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.

For example, the composition of the present disclosure can take the form of one of the following: juice; beverages containing whey protein: health tea or herbal tea, cocoa drink, coffee drink, yogurt and/or drinking yogurt, cheese, ice cream, dessert, candy, biscuits, cake, cake mix or cake filling, snack, fruit filling, cake or donut icing, ready-to-eat bakery cream, biscuit filling, ready-to-use bakery filling, low-calorie filling, adult nutritional beverage, acidified soy/juice drink, nutrition bar or health bar, beverage powder, energy drink, sublingual, soft candy, calcium-fortified soy milk or calcium-fortified coffee beverage.

Food ingredients

The composition of the present disclosure may take the form of a food ingredient and/or a feed ingredient.

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

The food ingredient may be in the form of a liquid, a suspension or a solid, depending on the use and/or the mode of application and/or the mode of administration.

Functional Foods

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 able to provide a nutritional effect, but is also able to deliver further beneficial effects to the consumer.

Accordingly, functional foods are ordinary foods that have incorporated therein components or ingredients (such as those described herein) that impart specific functions to the food other than purely nutritional effects - such as medical or physiological benefits.

While no legal definition of functional foods exists, most parties interested in the field agree that they are foods marketed as having specific health effects beyond basic nutritional effects.

Some functional foods are nutraceuticals. Here, the term "nutraceutical" means food that not only provides nutritional effects and/or taste satisfaction, but also delivers therapeutic (or other beneficial) effects to consumers. Nutraceuticals cross the traditional dividing line between food and medicine.

Medical food

The compositions of the present disclosure may take the form of a medical food. "Medical food" means a food that is formulated for consumption or administration with or without a physician's supervision and is intended for specific dietary management or conditions for which unique nutritional requirements have been established by medical evaluation based on recognized scientific principles.

How to use

In certain embodiments, paraxanthine can be combined with tyrosine and/or taurine, and in certain embodiments, can be combined with one or more other chemical compounds (e.g., other active ingredients) to provide a variety of positive effects in the subject. By changing the dosage of the paraxanthine and/or chemical compound with which it is combined, various physiological effects can be selected. The composition may mainly provide a single benefit, or may provide multiple benefits simultaneously. Depending on the object 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 is between about 1 and about 14,500 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) administered in single or multiple doses. 0 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 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, about 14,000, or about 14,5000 mg, etc., or any range or value therein)/object.

In certain embodiments, paraxanthine and tyrosine and/or taurine can be administered to a subject as part of a single composition. In further embodiments, paraxanthine and tyrosine and/or taurine are administered simultaneously or sequentially as separate compositions.

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 the subject needs to enhance energy, motor or cognitive performance, etc.).

Sports performance

Further disclosed herein is a method for enhancing performance or energy in an object, comprising administering a composition disclosed herein to an object. As used herein, the term "enhanced performance" is intended to mean any improvement in performance. Performance can be evaluated in any manner. Some enhancements are easily measured. For example, in a timing event, the improved time can evaluate the enhanced performance. Some performance enhancement properties can be subjectively judged by athletes or performers or observers. In these cases, the enhanced performance means that the 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 professional or recreational activity in which a performer, such as an athlete, exerts physical action, such as running, swimming, golf, bowling, archery, rugby, baseball, basketball, soccer, hiking, cycling, dancing, etc. In some cases, athletic performance is improved by improving endurance in an object. In other words, the administration of the disclosed composition improves the endurance level of the object, thereby enhancing the athletic performance of the object. In a further embodiment, the composition is administered to the object to increase cognitive performance, which thereby improves athletic performance.

In certain embodiments, following administration of the composition, the subject experiences an improvement in at least one of mood, energy, focus, attention, or sexual desire, or a reduction in at least one of anxiety, fatigue, perceived effort, or perceived pain.

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

Further disclosed herein is a method for increasing exercise tolerance in a subject, comprising administering a composition disclosed herein to the subject. In certain implementations, the composition administered to the subject comprises paraxanthine and tyrosine. In an exemplary implementation, relative to the administration of independent paraxanthine or 1-methylxanthine, the administration of paraxanthine and tyrosine produces a synergistic increase in exercise tolerance in the subject.

Further disclosed herein is a method for increasing exercise tolerance in a subject, comprising administering a composition disclosed herein to the subject. In certain implementations, the composition administered to the subject comprises paraxanthine and taurine. In an exemplary implementation, the administration of paraxanthine and taurine produces a synergistic increase in exercise tolerance in the subject relative to the administration of a single paraxanthine or 1-methylxanthine.

According to further embodiments, administering the disclosed composition to a subject increases the subject's perceived energy level. In an exemplary implementation, the subject experiences at least about a 5% increase in energy. According to certain embodiments, the administered composition further comprises (in addition to paraxanthine and/or tyrosine and/or taurine) 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, Paullinia cupana, Plathymiscium floribundum, tetrahydrocurcumin, and Solanum asperum and/or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, huperzine A, theophylline, methyl macrocarpine, B12, sulbutiamine, magnolia bark, ketones, MCTs, omega 3's, lutein, zeaxanthin and n-acetyl tyrosine, acetyl-L-carnitine and/or combinations thereof.

In certain embodiments, the subject's perceived energy level increases by about 2% to about 50%. In further embodiments, the subject's perceived energy level increases by about 5% to about 30%. In still further embodiments, the subject's perceived energy level increases by about 10% to about 25%.

Muscle function

Further disclosed herein is a method for increasing muscle function in an object by administering a composition disclosed herein to an object. In some aspects, disclosed herein is a method for promoting muscle growth by administering an effective amount of one or more compositions disclosed herein. In some further aspects, the administration of an effective amount of the disclosed composition results in higher levels of myosin synthesis (MPS) in an object. In yet further aspects, the administration of an effective amount of the disclosed composition results in improved muscle hyperplasia in an object.

In certain aspects, disclosed herein is a method of promoting muscle growth by administering an effective amount of one or more compositions disclosed herein. In certain further aspects, administration of an effective amount of the disclosed compositions results in higher levels of myosin synthesis (MPS) in a subject. In yet further aspects, administration of an effective amount of the disclosed compositions results in improved muscle hyperplasia in a subject.

According to certain embodiments, the compositions disclosed herein can be administered in conjunction with a strength training regimen. As will be appreciated by those skilled in the art, administration of an effective amount of the disclosed compositions results in improved strength and improved athletic performance/ergogenesis in a subject.

In one aspect, the disclosed compounds inhibit muscle atrophy. In a further aspect, the disclosed compounds increase muscle mass. In a still further aspect, the disclosed compounds induce muscle hypertrophy. In a still further aspect, the disclosed compounds inhibit muscle atrophy and increase muscle mass. In an even further aspect, the disclosed compounds inhibit muscle atrophy and induce muscle hypertrophy. In a further aspect, the inhibition of muscle atrophy is in a subject. In an even further aspect, the increase in muscle mass is in a subject. In a still further aspect, the subject is a mammal. In a still further aspect, the mammal is a human.

In certain aspects, administration of the disclosed compositions is effective in preventing or treating age-related muscle atrophy or sarcopenia. In further aspects, administration of the disclosed compositions is effective in preventing or treating muscle atrophy associated with muscle immobilization, such as muscle atrophy that frequently occurs during casting of fractured bones. In further aspects, administration of the disclosed compositions is effective in preventing or treating muscle atrophy associated with diseases such as cancer (also known as cachexia).

According to certain aspects, the composition is administered to a subject suffering from sarcopenia. In various aspects, the composition is administered in a therapeutically effective amount. In further aspects, the composition is administered in a prophylactically effective amount (e.g., administered to a subject at risk of developing sarcopenia, cachexia, or immobilization-induced atrophy).

In some aspects, the composition further comprises one or more additional active ingredients to further enhance muscle strength, size and/or muscle function. In certain embodiments, one or more additional active ingredients are amino acids. According to certain embodiments, amino acids are selected from branched-chain amino acids (BCAA), including but not limited to isoleucine, leucine and valine. In further embodiments, amino acids are selected from essential amino acids, including but not limited to histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine. In further embodiments, amino acids are selected from conditional essential amino acids, including but not limited to arginine, cysteine, glutamine, glycine, proline, ergothioneine and tyrosine. According to certain embodiments, conditional essential amino acids are tyrosine. In further embodiments, amino acids are selected from non-essential amino acids, including but not limited to alanine, aspartic acid, asparagine, glutamic acid, serine, selenocysteine and pyrrolysine. In a further embodiment, the amino acid derivative is selected from creatine, carnitine, β-alanine, taurine, β-hydroxy β-methylbutyrate, L-arginine, ω-3 fatty acids, vitamin D, whey protein, BAIBA and other protein extracts from animal, vegetable or fermentation sources.

According to exemplary aspects of these embodiments, this can reduce fatigue, improve energy, increase activity and improve alertness. In further embodiments, the administration of the disclosed composition is cardioprotective. In further embodiments, the administration of the disclosed composition improves muscle contraction and muscle performance. In exemplary aspects of these embodiments, muscle performance is enhanced by increasing potassium (K+) transport into skeletal muscle. In further aspects, muscle performance is enhanced by increasing intracellular calcium (e.g., via ryanodine receptor (RyR) activation).

In certain aspects of the foregoing embodiments wherein the composition comprises effective amounts of tyrosine and paraxanthine, administration of paraxanthine and tyrosine produces a synergistic increase in muscle size and/or function in a subject relative to administration of paraxanthine or tyrosine alone.

In certain aspects of the foregoing embodiments wherein the composition comprises effective amounts of taurine and paraxanthine, administration of paraxanthine and taurine produces a synergistic increase in muscle size and/or function in a subject relative to administration of paraxanthine or taurine alone.

Cognitive function

Disclosed herein are methods of enhancing cognitive function in a subject, comprising administering to the subject 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, attention set shifting, delayed reinforcement learning, reversal learning, temporal integration of voluntary behavior, processing speed, reasoning, problem solving, and/or social cognition.

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

In further embodiments, administration of the disclosed compositions increases attention.

According to certain embodiments, the composition of the method for enhancing cognitive function disclosed herein further comprises N-acetyl tyrosine, taurine, huperzine A, acetyl-L-carnitine, CDP choline, alpha GPC, choline bitartrate, choline citrate, B12, caffeine, methyl macrocarpon, theophylline, paraxanthine, theobromine, ashwagandha, rhodiola rosea, lutein, zeaxanthin, fish oil, creatine, ginseng, hericium erinaceus, 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.

In certain embodiments, the subject has experienced age-related cognitive decline. In an exemplary implementation, the composition is administered to the subject to increase the BDNF level in the subject. According to certain embodiments, the composition is administered to the subject to increase the brain-derived neurotrophic factor (BDNF) level in the subject. In an exemplary implementation, the BDNF level is increased by about 5% to about 40%. In a further embodiment, the BDNF level is increased by at least about 15%. In a further embodiment, the composition is administered to the subject to increase other neurotrophic factors, such as neuronal growth factor (NGF). In a further embodiment, the composition is administered to the subject to increase the mTOR level in the CNS.

Treatment

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

Further disclosed herein is a method for treating mood disorders by administering a composition disclosed herein to an object in need thereof. In certain embodiments, mood disorders are selected from clinical depression, postpartum depression or postpartum depression, perinatal depression, atypical depression, melancholic depression, psychotic major depression, tension depression, seasonal affective disorder, dysthymia, double depression, depressive personality disorder, recurrent brief depression, mild depressive disorder, bipolar disorder or manic depression, depression caused by chronic medical conditions, comorbid depression, refractory depression, refractory depression, suicidal tendencies, suicidal ideation or suicidal behavior. In some embodiments, the methods described herein provide therapeutic effects for objects suffering from depression (e.g., moderate or severe depression). In some embodiments, mood disorders are associated with diseases or conditions described herein.

In certain embodiments, the mood disorder is depression.In an exemplary implementation, the subject has been diagnosed with depression or is at risk of depression.

Further disclosed herein are methods for treating anxiety in a subject in need thereof by administering to a subject in need thereof a composition disclosed herein. In certain embodiments, the anxiety disorder is selected from: generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, phobia, post-traumatic stress disorder. As will be appreciated by those skilled in the art, anxiety disorders are a general term covering several different forms of abnormal and pathological fear and anxiety.

According to certain embodiments, the composition is administered in a therapeutically effective amount. In further embodiments, the composition is administered in a prophylactically effective amount.

In certain embodiments, the composition for use in the method of treating a mood disorder or an anxiety disorder further comprises at least one ingredient selected from L-theanine, phosphatidylcholine, alpha-GPC (L-alpha glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, Bacopa monnieri, phosphatidylserine, pilocarpine and cevimeline, abaca, lily grass, guarana, granadilla, tetrahydrocurcumin and Solanum asperum and/or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, magnolia bark, theanine, phosphatidylserine, ashwagandha, rhodiola rosea, Mucuna pruriens, contorted mesembryanthemum, 5-HTP, tryptophan, saffron, vitamin D, SAMe, Hericium erinaceus and/or huperzine A.

Further disclosed herein are methods for treating or preventing age-related cognitive decline in a subject in need thereof, comprising administering to the subject 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 voluntary behavior, processing speed, reasoning, problem solving, and/or social cognition.

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

In certain aspects, the disclosed compositions are neuroprotectants. In certain embodiments, administering the disclosed compositions to a subject in need thereof is neuroprotective. In exemplary aspects of these embodiments, such neuroprotection is in the form of protection from dopaminergic cell death.

According to further embodiments, the disclosed compositions can be used to treat geriatric depression. In exemplary embodiments, the compositions are effective in treating subjects suffering from geriatric depression of primary, vascular or traumatic origin. As well as mental decline in the elderly.

Administration of the disclosed compositions to a subject may include any method of providing a pharmaceutical formulation to a subject. Such methods are well known to those skilled in the art and include, but are not limited to, oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intravaginal administration, ophthalmic administration, intraauricular administration, intracerebral administration, rectal administration, sublingual administration, intradermal administration, buccal administration, and parenteral administration, including injections 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 further various aspects, the formulation may be administered prophylactically; that is, administered to prevent a disease or condition.

In another embodiment, the combination of paraxanthine and tyrosine and/or taurine 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 reduced appetite.

The advantage of using the disclosed composition is that the likelihood of an individual developing tolerance to the chemical composition is reduced. That is, the individual may not become desensitized to the induced effects. According to certain aspects, the disclosed composition containing a combination of paraxanthine and tyrosine and/or taurine has at least the following significant advantages over the administration of a composition containing a comparable dose of caffeine. The combination of paraxanthine and tyrosine and/or taurine has substantially lower toxicity. The combination of paraxanthine and tyrosine has greater stability (e.g., does not lose effectiveness over a period of time like caffeine). The composition containing a combination of paraxanthine and tyrosine and/or taurine is a more powerful wakefulness agent (in certain embodiments, via adenosine receptor antagonism). Further, the composition containing a combination of paraxanthine and tyrosine and/or taurine enhances striatal dopaminergic tone. Further, the combination of paraxanthine and tyrosine and/or taurine does not produce sleep rebound. Further, the combination of paraxanthine and tyrosine and/or taurine does not produce withdrawal effects that frequently occur for caffeine after cessation of use. Further, the combination of paraxanthine and tyrosine and/or taurine does not enhance anxiety. Still further, the bitterness of the combination of paraxanthine and tyrosine and/or taurine is less than that of caffeine. Even further, the combination of paraxanthine and tyrosine and/or taurine is effective for a larger portion of the population than caffeine. In another embodiment, the combination of paraxanthine and tyrosine and/or taurine can be used at higher dosage levels and/or used together with a synergistic compound.

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 dosage levels, compositions containing a combination of paraxanthine and tyrosine and/or taurine can be noradrenergic and dopaminergic and can show increased adenosine receptor inhibition.

In another embodiment, paraxanthine and tyrosine and/or taurine are combined with ephedrine, caffeine, salicylic acid, etc. The aforementioned combination can produce a synergistic effect with the stimulating effect of the combination of paraxanthine and tyrosine. For example, in certain embodiments, paraxanthine and tyrosine can be combined with caffeine in a much smaller amount to regulate the overstimulating effect of caffeine, thereby stabilizing heart rate and other metabolic activities. That is, the combination of paraxanthine and tyrosine and/or taurine and caffeine can result in such a composition, which gives the concentration and energy increase induced by caffeine, but without the higher heart rate and blood pressure regulated by the effect of caffeine of the combination of paraxanthine and tyrosine and/or taurine. Therefore, the combination may result in enhanced consciousness and calmness without the tension that caffeine may cause.

In another embodiment, the combination of paraxanthine and tyrosine can be used as a topical agent for incorporation into a body cream or lotion to produce a cream or lotion for whitening skin, tightening skin and/or improving skin elasticity. The topical agent containing the combination of paraxanthine and tyrosine and/or taurine can also be used to promote localized transdermal fat loss. Such compositions can also be used in creams or lotions to promote localized enhanced metabolism and/or enhanced heat production.

According to further embodiments, paraxanthine and tyrosine can be combined with one or more analgesics and/or anti-inflammatory agents. In an exemplary implementation, paraxanthine and tyrosine and/or taurine are combined with the following: ibuprofen, salicylic acid, anti-inflammatory agents, salicin, fish oil (ω-3 fatty acids and specific small lipid pro-inflammatory degradative derivatives), sour cherry, krill oil, astaxanthin, proteolytic enzymes, glucosamine sulfate, chondroitin sulfate, MSM (methylsulfonylmethane), SAMe (S-adenosylmethionine), ASU (avocado soy unsaponifiable fraction), cetyl myristate, sickle fruit lentil and/or triterpenes.

The dosage range of the combination of paraxanthine and tyrosine and/or taurine can be from about 100 mg to about 3000 mg. In another embodiment, the range can be from about 500 mg to about 2500 mg. In a further embodiment, the combined dose of paraxanthine and tyrosine is about 600 mg. In another embodiment, the range can be at least 10% to 90% paraxanthine and 90% to 10% taurine, respectively.

In certain embodiments, the composition comprises paraxanthine and tyrosine 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 tyrosine is provided in an amount of about 500 mg to about 2000 mg.

In an exemplary implementation, the composition is administered at a dosage of about 100 mg paraxanthine and about 500 mg tyrosine.

In another embodiment, the combination of paraxanthine and tyrosine and/or taurine is combined with one or more bioavailability enhancers. In an exemplary embodiment, bioavailability enhancers include, but are not limited to, piperine, piperine, black pepper, bergamot, dihydroxybergamot (CYP3A4 inhibitor), flavonoids (including hesperidin, naringin, tangeretin, quercetin, and nobiletin both in isolation and in combination), pterostilbene, fisetin, nanoencapsulation, microencapsulation, liposomes, and/or phospholipid complexes. The enhancer that is combined with the combination of paraxanthine and tyrosine may depend on what properties of the combination of paraxanthine and tyrosine and/or taurine are desired for a particular use.

In another embodiment, the combination of paraxanthine and tyrosine can be administered using one or more delivery methods, including, for example, transdermal patches and/or creams, easily mixable powders, intravenous methods, capsules, tablets, liquids (including liquids for mixing with other beverages), soft gel capsules, injectable forms, and/or cosmetic applications, including soaps, lotions, and shampoos. The anti-inflammatory properties of the combination of paraxanthine and tyrosine may be desirable for a variety of topical applications.

Administration of the disclosed compositions to a subject may include any method of providing a pharmaceutical formulation to a subject. Such methods are well known to those skilled in the art and include, but are not limited to, oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intravaginal administration, ophthalmic administration, intraauricular administration, intracerebral administration, rectal administration, sublingual administration, intradermal administration, buccal administration, and parenteral administration, including injections 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 further various aspects, the formulation may be administered prophylactically; that is, administered to prevent a disease or condition.

Various aspects and embodiments of the present invention are defined by the following numbered technical solutions:

1. A composition comprising paraxanthine and tyrosine.

2. The composition of technical solution 1, further comprising one or more active ingredients selected from the following: 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, co-crystallized products of piperine, piperine, black pepper, bergamot, dihydroxybergamot (CYP3A4), flavonoids (naringin, hesperidin, nobiletin, tangeretin, quercetin), pterostilbene, fisetin, phospholipid complex, salicin, fish oil ( _ω Omega-3 fatty acids and specific small lipid pro-inflammatory epoxide derivatives), oxylipids, tart cherry, krill oil, astaxanthin, proteolytic enzymes, glucosamine sulfate, chondroitin sulfate, MSM (methylsulfonylmethane), SAMe (S-adenosylmethionine), ASU (avocado soy unsaponifiable fraction), cetyl myristate, lentil, triterpenes, catechu, andrographis paniculata, scutellaria baicalensis, agmatine sulfate, stinging nettle, sea buckthorn, curcumin, quislin, frankincense, wasabi (mustard extract for tea tree oil), emu oil, arnica, mango (Anacardiaceae), caltrop, ginger (ginger and gingerols/shogaols), cactus, caffeine, yohimbine, methyl synephrine, synephrine, theobromine, flavonoids, tocopherols, theophylline, alpha-yohimbine, conjugated linoleic acid (CLA), octopamine, evodiamine, passion flower, red pepper, cayenne pepper, raspberry ketones, Indian myrrh, green tea, guarana, kola nut, beta-phenylethylamine, acacia, forskolin (Coleus forskohlii), theophylline, synephrine, yohimbe, rhodiola rosea, ashwagandha, ginseng, ginkgo, Siberian ginseng, astragalus, licorice, green tea, reishi, dehydroepiandrosterone (DHEA), pregnenolone, N-acetyl, grape Urone lactone, acetyl-L-carnitine, 5-hydroxytryptophan, tryptophan, phenylethylamine, contortus (and contortus alkaloids), Dendrobium species, Acacia, PQQ (pyrroloquinoline quinone), ubiquinone (01), nicotinamide riboside, picamiron, huperzine A (Chinese club moss or Huperzia serrata), L-dopa, Mucuna pruriens and forskolin (Coleus forskohlii), 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, ornithine, citrulline, pyruvate, Acanthopanax senticosus, D-ribose, whey protein, trimethylglycine, arginine, HMB (beta-hydroxy beta-methylbutyrate), Milk protein, Schisandra chinensis, leucine, betacyanin, leucine, L-carnitine, sodium bicarbonate, arachidonic acid, beta-alanine, rape steroids, alanyl-glutamine, deer grass, casein, ecdysteroids, creatine, branched chain amino acids, beetroot, coffee, nitrates, Korean ginseng, clenbuterol, alpha-GPC, valine, colostrum, cyperus rotundus, ashwagandha, terminalia arjuna, egg, ursolic acid, isoleucine, medium chain triglycerides, glutamine, zinc, vitamin D, maca, Schisandra chinensis, nicotinamide mononucleotide (NMN), exogenous ketones, ergothioneine, berberine, dihydroberberine, and combinations thereof.

3. The composition of technical solution 1, further comprising a combination of paraxanthine and a tyrosine homologue or a combination of paraxanthine and a tyrosine analogue.

4. The composition of technical solution 3, wherein the combination of paraxanthine homologues or analogues is selected from caffeine, 1-methylxanthine, a combination of paraxanthine and 7-methylxanthine, paraxanthine, theobromine, theophylline, macrocarpine, methyl macrocarpine and combinations thereof.

5. The composition of technical solution 4, wherein the paraxanthine homologue or analogue is caffeine.

6. The composition of technical solution 5, wherein the effective dose of caffeine is lower than the effective dose of caffeine in the composition not containing the combination of paraxanthine and tyrosine.

7. The composition of technical solution 3, wherein the tyrosine homologue or analogue is N-acetyl-L-tyrosine, glycyl-L-tyrosine, N-acetyl-L-tyrosine ethyl ester or N-acetyl-L-tyrosine methyl ester.

8. The composition of technical solution 1, wherein tyrosine exists in a polymerized form.

9. The composition of technical solution 8, wherein tyrosine exists as dityrosine (Tyr-Tyr), trityrosine (Tyr-Tyr-Tyr), tetratyrosine (Tyr-Tyr-Tyr-Tyr) or a peptide containing the foregoing.

10. The composition of technical solution 8, wherein the tyrosine exists as lysyltyrosine or leucine-tyrosine.

11. The composition of claim 8, wherein tyrosine is present in a dipeptide having the structure L-Tyr-X, wherein X is an amino acid.

12. The composition of any preceding technical solution, wherein the paraxanthine and tyrosine are present in a ratio of about 1:4 to about 1:30.

13. The composition of technical solution 12, wherein the paraxanthine and tyrosine are present in a ratio of about 1:4 to about 1:10.

14. A composition comprising paraxanthine and taurine.

15. The composition of technical solution 14, further comprising one or more active ingredients selected from the following: 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, co-crystallized products of piperine, piperine, black pepper, bergamot, dihydroxybergamot (CYP3A4), flavonoids (naringin, hesperidin, nobiletin, tangeretin, quercetin), pterostilbene, lacquer yellow , phospholipid complex, salicin, fish oil (omega-3 fatty acids and specific small lipid pro-inflammatory epoxide derivatives), oxylipids, tart cherry, krill oil, astaxanthin, proteolytic enzymes, glucosamine sulfate, chondroitin sulfate, MSM (methylsulfonylmethane), SAMe (S-adenosylmethionine), ASU (avocado soy unsaponifiable fraction), cetyl myristate, lentil, triterpenoids, catechu, andrographis paniculata, scutellaria baicalensis, agmatine sulfate, stinging nettle, sea buckthorn, curcumin, quislin, frankincense, wasabi (mustard extract for tea tree oil), emu oil, arnica, mango (anacardiaceae), calendula officinalis, ginger (ginger and gingerol/shogaol), cactus, caffeine, yohimbine, methyl synephrine, synephrine, theobromine, flavonoids, tocopherol, theophylline, alpha-yohimbine, conjugated Linoleic acid (CLA), octopamine, evodiamine, passionflower, red pepper, cayenne pepper, raspberry ketone, Indian myrrh, green tea, guarana, cola nut, beta-phenylethylamine, acacia, forskolin (Coleus forskohlii), theophylline, synephrine, yohimbe, rhodiola rosea, ashwagandha, ginseng, ginkgo, Siberian ginseng, astragalus, licorice, green tea, reishi, dehydroepiandrosterone (DHEA), pregnenolone, N -Acetyltyrosine, glucuronolactone, acetyl-L-carnitine, 5-hydroxytryptophan, tryptophan, phenylethylamine, contortus (and contortus alkaloids), Dendrobium species, Acacia, PQQ (pyrroloquinoline quinone), ubiquinone (01), nicotinamide riboside, picamiron, huperzine A (Chinese club moss or Huperzia serrata), L-dopa, Mucuna pruriens and forskolin (Coleus forskohlii), 2-(dimethylamino)- Ethanol (DMAE), DMAE bitartrate, ornithine, citrulline, pyruvate, Acanthopanax, D-ribose, whey protein, trimethylglycine, arginine, HMB (beta-hydroxy beta-methylbutyrate), milk protein, Schisandra, leucine, betaine, leucine, L-carnitine, sodium bicarbonate, arachidonic acid, beta-alanine, rape steroids, alanyl glutamine, deer grass, casein, ecdysteroids, creatine, branched chain amino acids, beetroot, coffee, nitrates, Korean ginseng, clenbuterol, alpha-GPC, valine, colostrum, Ceylon spatholobus, Ashwagandha, Terminalia arjuna, egg, ursolic acid, isoleucine, medium chain triglycerides, glutamine, zinc, vitamin D, maca, Schisandra, nicotinamide mononucleotide (NMN), exogenous ketones, ergothioneine, berberine, dihydroberberine, and combinations thereof.

16. The composition of technical solutions 14-15, wherein paraxanthine and taurine are present in a ratio of about 1:5.

17. The composition of technical solutions 14-16, further comprising a combination of paraxanthine homologues and/or paraxanthine analogs.

18. The composition of technical solution 17, wherein the combination of paraxanthine homologues or analogues is selected from caffeine, 1-methylxanthine, a combination of paraxanthine and 7-methylxanthine, paraxanthine, theobromine, theophylline, caffeine, methyl caffeine and combinations thereof.

19. The composition of technical solution 18, wherein the paraxanthine homologue or analogue is caffeine.

20. The composition of technical solution 19, wherein the effective dose of caffeine is lower than the effective dose of caffeine in a composition not containing the combination of paraxanthine and tyrosine.

21. The composition of any preceding technical solution, wherein the composition is a powder.

22. The composition of any preceding technical solution, wherein the composition is a dietary supplement, and the supplement is a solid oral dosage form.

23. The composition of any preceding technical solution, wherein the composition is formulated for topical administration.

24. The composition of any of the preceding technical solutions except technical solutions 5-6 and 19-20, wherein the composition is substantially free of caffeine.

25. A method for improving energy in a subject, comprising: administering the composition of technical scheme 1-24 to the subject.

26. The method of technical solution 25, wherein after administration of the composition, the subject experiences an improvement in at least one of mood, energy, concentration, focus, or sexual desire, or a reduction in at least one of anxiety, fatigue, perceived effort, or perceived pain.

27. The method of technical solution 26, wherein after continued administration to the subject, the composition does not produce dependence in the subject and/or does not produce withdrawal effects in the subject when continued use is stopped.

28. The method of technical solution 25, wherein the amount of paraxanthine provided is about 50 mg to about 400 mg.

29. The method of technical solution 25, wherein the amount of tyrosine provided is about 250 mg to about 13,500 mg.

30. The method of technical solution 25, wherein the amount of tyrosine provided is about 100-150 mg/kg body weight of the subject.

31. The method of claim 25, wherein the subject experiences at least about 6% reduction in fatigue.

32. The method of claim 25, wherein the subject experiences at least about a 5% increase in energy.

33. The method of technical solution 25, wherein the composition further comprises at least one ingredient selected from the following: L-theanine, phosphatidylcholine, α-GPC (L-α glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, Bacopa monnieri, phosphatidylserine, pilocarpine and cevimeline, azul, spatholobi, guarana, largium wilfordii, tetrahydrocurcumin and Solanum asperum and/or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, Magnolia officinalis, theanine, phosphatidylserine, ashwagandha, Rhodiola rosea, Mucuna pruriens, contorted mesembryanthemum, 5-HTP, tryptophan, saffron, vitamin D, SAMe, Hericium erinaceus and huperzine A.

34. A method for increasing exercise endurance in a subject, comprising administering to the subject the composition of any one of technical solutions 1-24.

35. The method of technical solution 34, wherein the composition is the composition of any one of technical solutions 1-11, and wherein the administration of paraxanthine and tyrosine produces a synergistic increase in exercise endurance in the subject relative to the administration of paraxanthine or tyrosine alone.

36. The method of technical solution 35, wherein the amount of tyrosine provided is about 250 mg to about 13,500 mg.

37. The method of technical solution 35, wherein the amount of tyrosine provided is about 100-150 mg/kg body weight of the subject.

38. The method of technical solution 34, wherein the composition is the composition of any one of technical solutions 12-18, and wherein the administration of paraxanthine and taurine produces a synergistic increase in exercise endurance in the subject relative to the administration of paraxanthine or taurine alone.

39. A method of treating a condition in a subject in need thereof, comprising administering to the subject the composition of any one of technical solutions 1-24.

40. The method of technical solution 39, wherein the condition is selected from narcolepsy, epilepsy, attention deficit disorder, attention deficit hyperactivity syndrome (ADHD), cognitive deficit disorder, paralysis, uncontrolled anger, migraine, substance abuse addiction, eating disorders, depression, anxiety, traumatic head injury (TBI), concussion, Parkinson's disease, Alzheimer's disease and dementia.

41. The method of claim 39, wherein the condition is a mood disorder.

42. The method of technical solution 41, wherein the mood disorder is depression.

43. The method of technical solution 42, wherein the subject has been diagnosed with depression or is at risk of depression.

44. The method of claim 40, wherein the condition is an anxiety disorder.

45. The method of technical solution 40, wherein the composition is administered in a therapeutically effective amount.

46. The method of technical solution 40, wherein the composition is administered in a prophylactically effective amount.

47. The method of technical solution 40, wherein the composition comprises paraxanthine in an amount of about 2 mg to about 800 mg.

48. The method of technical solution 39, wherein the composition further comprises at least one ingredient selected from the following: L-theanine, phosphatidylcholine, α-GPC (L-α glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, Bacopa monnieri, phosphatidylserine, pilocarpine and cevimeline, azul, spatholobi, guarana, largium multiflorum, tetrahydrocurcumin and Solanum asperum and/or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, Magnolia officinalis, theanine, phosphatidylserine, ashwagandha, Rhodiola rosea, n-acetyltyrosine, Mucuna pruriens, contorted mesembryanthemum, 5-HTP, tryptophan, saffron, vitamin D, SAMe, Hericium erinaceus and/or huperzine A.

49. A method of enhancing attention in a subject in need thereof, comprising administering the composition of any one of technical solutions 1-24.

50. A method for improving working memory in a subject in need thereof, comprising administering to the subject the composition of any one of technical solutions 1-24.

51. A method for improving cognitive performance in a subject, comprising administering the composition of any one of technical schemes 1-24.

52. The method of technical solution 51, wherein the improved cognitive function is measured by an increase 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, attention set shifting, delayed reinforcement learning, reversal learning, temporal integration of voluntary behavior, processing speed, reasoning, problem solving and/or social cognition.

53. A method for increasing muscle function in a subject, comprising: administering to the subject the composition of any one of technical solutions 1-24.

54. The method of technical solution 53, wherein the composition further comprises one or more compounds selected from the following: isoleucine, leucine and valine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, creatine, arginine, cysteine, glutamine, glycine, proline, carnitine, β-alanine and β-hydroxy β-methylbutyric acid.

55. A nutritional supplement for improving muscle strength, muscle size and/or muscle function, comprising the composition of any one of technical solutions 1-24.

56. The nutritional supplement of technical solution 55, wherein the nutritional supplement is a powder or a capsule.

57. The nutritional supplement of technical solution 55, wherein the nutritional supplement is a functional food.

58. The nutritional supplement of technical solution 57, wherein the functional food is a beverage, a nutrition bar, a yogurt or a cereal food.

59. The nutritional supplement of technical solution 55 further comprises one or more compounds selected from the following: isoleucine, leucine and valine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, creatine, arginine, cysteine, glutamine, glycine, proline, carnitine, β-alanine, β-hydroxy β-methylbutyric acid, L-arginine, ω-3 fatty acids, vitamin D, whey protein and other protein extracts from animal, plant or fermentation sources.

60. A method of increasing muscle size in a subject, comprising administering to a subject in need thereof an effective amount of the composition of any one of technical solutions 1-24.

61. The method of technical solution 60, wherein the composition is the composition of any one of technical solutions 1-11, and wherein the administration of paraxanthine and tyrosine produces a synergistic increase in muscle size in a subject relative to the administration of paraxanthine or tyrosine alone.

62. The method of technical solution 61, wherein the amount of tyrosine provided is about 250 mg to about 13,500 mg.

63. The method of technical solution 61, wherein the amount of tyrosine provided is about 100-150 mg/kg body weight of the subject.

64. The method of technical solution 60, wherein the composition is the composition of any one of technical solutions 12-18, and wherein the administration of paraxanthine and taurine produces a synergistic increase in muscle size in a subject relative to the administration of paraxanthine or taurine alone.

65. A method for increasing energy in a subject, comprising administering to a subject in need thereof an effective amount of the composition of any one of technical solutions 1-24.

66. The method of technical solution 65, wherein the amount of paraxanthine administered is about 25 mg to about 800 mg.

67. The method of claim 65, wherein the subject experiences an increase in energy perception of at least about 5%.

68. The method of technical solution 65, wherein the subject experiences a reduction in at least one of anxiety, fatigue, perceived effort and/or perceived pain.

69. The method of technical solution 65, wherein the composition further comprises paraxanthine in an amount of about 2 mg to about 800 mg.

70. The method of technical solution 69, wherein the composition is the composition of any one of technical solutions 1-11, and wherein the administration of paraxanthine and tyrosine produces a synergistic increase in energy perception in the subject relative to the administration of comparable doses of paraxanthine or tyrosine alone.

71. The method of technical solution 70, wherein the amount of tyrosine provided is about 250 mg to about 13,500 mg.

72. The method of technical solution 70, wherein the amount of tyrosine provided is about 100-150 mg/kg body weight of the subject.

73. The method of technical solution 69, wherein the composition is the composition of any one of technical solutions 12-18, and wherein the administration of paraxanthine and taurine produces a synergistic increase in energy perception in the subject relative to the administration of comparable doses of paraxanthine or taurine alone.

74. The method of technical solution 65, wherein the composition further comprises at least one ingredient selected from the following: L-theanine, phosphatidylcholine, α-GPC (L-α glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, Bacopa monnieri, phosphatidylserine, pilocarpine and cevimeline, azul, spatholobi, guarana, largium multiflorum, tetrahydrocurcumin and Solanum asperum and/or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, Magnolia officinalis, theanine, phosphatidylserine, ashwagandha, Rhodiola rosea, n-acetyltyrosine, Mucuna pruriens, contorted mesembryanthemum, 5-HTP, tryptophan, saffron, vitamin D, SAMe, Hericium erinaceus and huperzine A.

75. The method of claim 65, wherein the composition is substantially free of caffeine.

76. A method for improving athletic performance in a subject, comprising administering to the subject a composition comprising an effective amount of the composition of any one of technical solutions 1-24.

77. The method of technical solution 75, wherein the amount of paraxanthine administered is about 50 mg to about 400 mg.

78. The method of claim 76, wherein athletic performance is increased by at least about 10%.

79. The method of claim 76, wherein the subject experiences increased endurance.

80. The method of technical solution 76, wherein the composition is the composition of any one of technical solutions 1-11, and wherein administration of the composition to a subject produces a synergistic increase in athletic performance as compared to administration of comparable doses of paraxanthine or tyrosine alone.

81. The method of technical solution 76, wherein the composition is the composition of any one of technical solutions 12-18, and wherein administration of the composition to a subject produces a synergistic increase in athletic performance compared to administration of comparable doses of paraxanthine or taurine alone.

82. The method of technical solution 76, wherein the composition further comprises at least one agent selected from the following: L-theanine, phosphatidylcholine, α-GPC (L-α glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, Bacopa monnieri, phosphatidylserine, pilocarpine and cevimeline, azulina, spatholobi, guarana, spatholobi, tetrahydrocurcumin and Solanum asperum and/or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, huperzine A, theophylline, methyl macrocarpon, B12, sulbutiamine, magnolia bark, ketones, MCT, ω3's, lutein, zeaxanthin and n-acetyltyrosine, acetyl-L-carnitine and/or combinations thereof.

Example

The following examples are presented to provide those of ordinary skill in the art with a complete disclosure and description of certain examples of how to prepare and evaluate 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, in light of this disclosure, it should be understood by those skilled in the art that many changes may be made in the specific embodiments disclosed and still obtain the same or similar results without departing from the spirit and scope of the present invention.

Example 1

Paraxanthine plus tyrosine

Cognition, memory, learning

1.1. Methods

Behavioral studies were performed in mice to examine learning and memory abilities by using Cook's pole climbing test.

Thirty-two 8-week-old male Swiss Albino mice were housed in an animal room under a 12:12 hour light-dark cycle, at a constant temperature (22 ± 3 ° C) and constant humidity (30%-70%), using a standard laboratory diet (Purina 5L79, 18% protein for rats and mice; PMI Nutrition International, Brentwood, MO, USA). Distilled water was provided ad libitum. All animal experiments were reviewed and approved by the Institutional Animal Ethical Committee (IAEC) of Radiant Research Services Pvt. Ltd (Bangalore, India). All studies were conducted in accordance with the guidelines of the committee for the purpose of controlling and supervising experiments on animals.

After one week of acclimatization, animals were randomized by body weight into four groups (n=8/group in each test) for once-daily oral treatment at approximately the same time each day (±1 hour) for 7 consecutive days: (1) vehicle control or (2) paraxanthine or (3) tyrosine or (4) tyrosine plus paraxanthine. The doses administered to mice were calculated using the US Food and Drug Administration human equivalent dose (HED), assuming a 60 kg human weight. The following HED was used in this study: 100 mg paraxanthine ( Ingenious Ingredients, LP Lewisville, TX, USA; mouse dose: 20.5 mg/kg bw/day) or 500 mg tyrosine (mouse dose: 102.75 mg/kg bw/day), or 500 mg tyrosine (mouse dose: 102.75 mg/kg bw/day) plus 100 mg paraxanthine ( Ingenious Ingredients, LP Lewisville, TX, USA; mouse dose: 20.5 mg/kg bw/day). 0.5% sodium carboxymethylcellulose was used as a vehicle, and test article formulations were prepared daily. Dosing was performed via oral gavage using a disposable polypropylene syringe with a sterile stainless steel gavage tube. Food intake was monitored daily, while water intake was ad libitum.

1.2. Cook’s Pole Climbing Test

Mice were trained in such a way that the animals had to climb up the pole (no shock zone) within 30 seconds to avoid electric shock. The electric shock was preceded by a 15-second buzzer sound. The animals were trained to climb up the pole when the buzzer sounded (conditioned avoidance response). Within a specific interval, 20 trials were given to each animal, and the average values of avoiding electric shock and errors were recorded. The trained animals were measured by conditioned avoidance response.

1.3. Induction of amnesia

Amnesia was induced by using scopolamine injections. Scopolamine is an anticholinergic and an attractive amnesic agent for identifying the effects of candidate anti-amnesic drugs. Scopolamine is a non-selective postsynaptic muscarinic receptor blocker and can cause cognitive impairment in rodents and humans by reducing the availability of ACH in the CNS in animals and humans. Scopolamine can induce significant deficits in cognitive performance during behavioral tests, making it an effective pharmacological model for inducing cognitive deficits. In this study to evaluate cognitive effects, mice were injected intraperitoneally with scopolamine to induce memory deficits.

2. Results

Mice treated with paraxanthine showed reversal of amnesia induced by scopolamine and improved memory and learning. The combination of paraxanthine and tyrosine showed a synergistic effect that exceeded that of either paraxanthine or tyrosine alone.

2.1. Supplementing the function of Cook's climbing pole test

The escape latency in the paraxanthine group (16.38 ± 2.33 seconds) was 46.3% faster than the control (6.38 ± 1.41 seconds). The escape latency in the tyrosine group (8.25 ± 1.04 seconds) was 30.6% faster than the control and 29.3% slower than paraxanthine. The escape latency in the paraxanthine plus tyrosine group (5.88 ± 0.83 seconds) was 50.5% faster than the control, 7.8% faster than paraxanthine alone, and 28.7% faster than tyrosine alone.

Example 2

Paraxanthine plus tyrosine

Sports and Active Nutrition, Sports Performance, Strength, Energy, Mood

1.1. Methods

Thirty-two 8-week-old male Swiss Albino mice were housed in an animal room under a 12:12 hour light-dark cycle, at a constant temperature (22 ± 3 ° C) and constant humidity (30%-70%), using a standard laboratory diet (Purina 5L79, 18% protein for rats and mice; PMI Nutrition International, Brentwood, MO, USA). Distilled water was provided ad libitum. All animal experiments were reviewed and approved by the Institutional Animal Ethical Committee (IAEC) of Radiant Research Services Pvt. Ltd (Bangalore, India). All studies were conducted in accordance with the guidelines of the committee for the purpose of controlling and supervising experiments on animals.

After one week of acclimatization, animals were randomized by body weight into four groups (n=8/group in each test) for once-daily oral treatment at approximately the same time each day (±1 hour) for 28 consecutive days: (1) vehicle control or (2) paraxanthine or (3) tyrosine or (4) tyrosine plus paraxanthine. The doses administered to mice were calculated using the U.S. Food and Drug Administration human equivalent dose (HED), assuming a 60 kg human weight. The following HED was used in this study: 100 mg paraxanthine ( Ingenious Ingredients, LP Lewisville, TX, USA; mouse dose: 20.5 mg/kg bw/day) or 500 mg tyrosine (mouse dose: 102.75 mg/kg bw/day), or 500 mg tyrosine (mouse dose: 102.75 mg/kg bw/day) plus 100 mg paraxanthine ( Ingenious Ingredients, L.P. Lewisville, TX, USA; mouse dose: 20.5 mg/kg bw/day). 0.5% sodium carboxymethylcellulose was used as a vehicle, and test article formulations were prepared daily. Dosing was performed via oral gavage using a disposable polypropylene syringe with a sterile stainless steel gavage tube. Food intake was monitored daily, while water intake was ad libitum.

1.2. Forelimb grip strength test

At the 0th day and the 28th day, forelimb grip strength was measured by using a stainless steel grid to evaluate muscle strength (Orchid Scientific & Innovative India Pvt Ltd, India). Grip strength was measured one hour after treatment. In brief, each mouse was first placed in a test room for ten minutes to acclimate. Each mouse was then placed on the top of a grip dynamometer grid to allow mice to grasp the grid with all four paws. The mouse was held by the base of the tail without pressing the grid downward. Then, by pulling the tail along the grip measurement axis, the animal was gently pulled back from the grid. The speed was slow enough to allow mice to develop resistance to pulling force, and once the mouse released the grid, the score (gf) displayed on the screen of the grip measurement was recorded. Each animal was tested independently three times, and the mean value of the three tests was calculated and recorded.

1.3. Exercise training

During the treatment period, complete training for 15 minutes in a swimming room at moderate room temperature. During the treatment period, animals are adapted to the program 1 hour after administration every day, for 5 days in a week. On the 28th day of treatment respectively, all animals are subjected to forced swimming test. Animals are forced to swim 30 minutes individually at room temperature in a glass jar, and the glass jar has a height of 20 cm, a diameter of 10 cm and injects fresh water to a depth of 15 cm. The parameter measured is the total time spent in active swimming (the total duration of animal swimming from beginning to end in the experimental period during the process).

2. Results

As shown in Figure 1, mice treated with paraxanthine showed improved strength over controls. Tyrosine improved strength to a lesser extent, however, the combination of paraxanthine and tyrosine showed a synergistic effect over either paraxanthine or tyrosine alone.

2.1. Effect of supplementation on forelimb grip strength

2.2. Effects of supplementation on energy and mood

Mice treated with paraxanthine showed improved energy and mood. The combination of paraxanthine and tyrosine showed synergistic benefits over paraxanthine and tyrosine alone.

The duration of activity/active swimming was synergistically longer in the combination group of paraxanthine and tyrosine (9.38 ± 1.30 min) compared to control (8.75 ± 1.39 min), +7.2%, tyrosine (8.88 ± 1.46 min), and paraxanthine (8.63 ± 1.92 min).

Example 3

Paraxanthine plus taurine

Energy, emotions

1.1. Methods

Twenty-four 8-week-old male Swiss Albino mice were housed in an animal room under a 12:12 hour light-dark cycle, at a constant temperature (22 ± 3 ° C) and constant humidity (30%-70%), using a standard laboratory diet (Purina 5L79, 18% protein for rats and mice; PMI Nutrition International, Brentwood, MO, USA). Distilled water was provided ad libitum. All animal experiments were reviewed and approved by the Institutional Animal Ethical Committee (IAEC) of Radiant Research Services Pvt. Ltd (Bangalore, India). All studies were conducted in accordance with the guidelines of the committee for the purpose of controlling and supervising experiments on animals.

After one week of acclimatization, animals were randomized by body weight into three groups (n=8/group in each test) for once-daily oral treatment at approximately the same time each day (±1 hour) for 28 consecutive days: (1) paraxanthine or (2) taurine or (3) taurine plus paraxanthine. The doses administered to mice were calculated using the U.S. Food and Drug Administration human equivalent dose (HED), assuming a 60 kg human weight. The following HED was used in this study: 100 mg paraxanthine ( Ingenious Ingredients, LP Lewisville, TX, USA; mouse dose: 20.5 mg/kg bw/day) or 500 mg taurine (mouse dose: 102.75 mg/kg bw/day), or 500 mg taurine (mouse dose: 102.75 mg/kg bw/day) plus 100 mg paraxanthine ( Ingenious Ingredients, LP Lewisville, TX, USA; mouse dose: 20.5 mg/kg bw/day). 0.5% sodium carboxymethylcellulose was used as a vehicle, and test article formulations were prepared daily. Dosing was performed via oral gavage using a disposable polypropylene syringe with a sterile stainless steel gavage tube. Food intake was monitored daily, while water intake was ad libitum.

1.2. Exercise training

During the treatment period, complete training 15 minutes in the swimming room at medium room temperature. During the treatment period, animals are adapted to the program every day in 1 hour after administration, 5 days in a week. When the 28th day of treatment respectively, all animals are subjected to forced swimming test. Animals are forced to swim 30 minutes individually in a glass jar at room temperature, and the glass jar has a height of 20cm, a diameter of 10cm and injects fresh water to a depth of 15cm. The measured parameter is the total time (the total duration of animal swimming from beginning to end in the experimental period during its process) and the immobile duration (the total time of animal immobile during its process) of active swimming spending.

2. Results

Mice treated with a combination of paraxanthine and taurine showed a synergistic effect that exceeded that of either paraxanthine or taurine alone.

2.1. Effects of supplementation on energy and mood

The duration of activity/active swimming was synergistically longer in the combination group of paraxanthine and taurine (8.75±1.04 min) compared to taurine (8.50±2.20 min) and paraxanthine (8.63±1.92 min).

The duration of immobility was synergistically shorter in the combination group of paraxanthine and taurine (21.25±1.04 minutes) compared to taurine (21.50±2.20 minutes) and paraxanthine (21.38±1.92 minutes).

Although multiple 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 can have modifications in various obvious aspects, all without departing from the spirit and scope of the present disclosure. Accordingly, the drawings and detailed description are to be regarded as illustrative and non-restrictive in nature.

Claims (19)

1. A dietary supplement comprising parathyroid xanthine and tyrosine, wherein the paratuanine and tyrosine are present in a ratio of from about 1:4 to about 1:30.

2. The dietary supplement of claim 1, further comprising a further 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), glycerol esters, propylene glycol, lauroyl polyethylene glycol derivatives, co-crystallized products of piperine, black pepper, bergamotin, dihydroxybergamotin (CYP 3 A4), flavonoids (naringin, hesperidin, nobiletin, hesperetin, quercetin), pterostilbene, fisetin, phospholipid complexes, salicin, fish oils (omega-3 fatty acids and specific small lipid pro-inflammatory resolution epoxide derivatives), oxidized lipids, sour cherries, krill oil, astaxanthin, proteolytic enzymes, glucosamine sulfate, chondroitin sulfate, MSM (methylsulfonylmethane), SAMe (S-adenosylmethionine), ASU (avocado soybean unsaponifiable fraction), cetyl myristate Fusarium oxysporum (Dolichos falcata), triterpenes, catechu, herba Andrographitis (Andrographis paniculata), scutellariae radix (Scutalleria baicalensis), agmatine sulfate, herba Urticae Cannabinae (STINGING NETTLE), fructus Hippophae (Sea Buckthorn), curcumin, herba Cynanchi Paniculati (Cissus Quadrilangularis), olibanum (Boswellia Serrata), herba Horseradish (Wasabia japonica) (mustard extract for tea tree oil), herba Polygoni Avicularis, and fructus Hippophae, Emu oil, arnica, mangosteen (MANGIFERA INDICA l.) (anaceae (ANACARDIACEAE)), short flower cucurbit (LAGENARIA BREVIFLORA), ginger (Zingiber officinale) (ginger and gingerol/shogaol), cactus (hoodia gordonii), caffeine, yohimbine, methyl synephrine, theobromine, flavonoids, tocopherols, theophylline, alpha-yohimbine, conjugated Linoleic Acid (CLA), octopamine, evodiamine, passion flower, red pepper, and the like, The ingredients include capsicum, raspberry ketone, myrrh, green tea, guarana, cola, beta-phenylethylamine, farnesoid (Acacia rigidula), forskolin (coleus forskohlii (Coleus forskohlli)), theophylline, synephrine, yohimbine, rhodiola rosea, cigar, ginseng, ginkgo biloba, siberian ginseng, astragalus, licorice, green tea, ganoderma lucidum, dehydroepiandrosterone (DHEA), pregnenolone, N-acetyl tyrosine, glucuronolactone, acetyl l-carnitine, 5-hydroxytryptophan, tryptophan, phenylethylamine, twisted stevia (Sceletium tortuosum) (and dencichine alkaloid), and the like, Dendrobe species (Dendrobium sp.), acacia, PQQ (pyrroloquinoline quinone), ubiquinone (01), nicotinamide riboside, picamilone, huperzine A (China shipina (Chinese clubmoss) or Huperzia serrata (Huperzia serrata)), levodopa, mucuna pruriens (Mucuna pruriens) and forskolin (Coleus forskohlii), 2- (dimethylamino) ethanol (DMAE), DMAE bitartrate, ornithine, citrulline, pyruvate, acanthopanax (Eleutherococcus senticosus), D-ribose, whey protein, trimethylglycine, arginine, HMB (beta-hydroxy beta-methylbutyric acid), milk protein, shizandra berry (SCHISANDRA CHINENSIS), leucine, betalain, leucine, sinc acid, L-carnitine, sodium bicarbonate, arachidonic acid, beta-alanine, brassinosteroids, alanylglutamine, deer grass (Rhaponticum carthamoides), casein, ecdysteroids, creatine, branched amino acids, beetroot, coffee, nitrate, korean ginseng (panaxginsen), clenbuterol, alpha-GPC, valine, colostrum, cassita stolonifera (Trichopus zeylanicus), withania somnifera, arjuna (TERMINALIA ARJUNA), egg, ursolic acid, isoleucine, medium chain triglycerides, glutamine, zinc, vitamin D, maca, schisandra (Schizandra), nicotinamide Mononucleotide (NMN), exogenous ketone, ergothioneine, berberine, dihydroberberine, and combinations thereof.

3. The dietary supplement of claim 1, further comprising a combination of a homolog of parathyroid hormone and tyrosine or a combination of a parathyroid hormone and tyrosine analog.

4. The dietary supplement of claim 3, wherein the tyrosine homolog or analog is N-acetyl-L-tyrosine, glycyl-L-tyrosine, N-acetyl-L-tyrosine ethyl ester, or N-acetyl-L-tyrosine methyl ester.

5. The dietary supplement of claim 1, wherein the tyrosine is present in a polymerized form, and wherein the polymerized form is di-tyrosine (Tyr-Tyr), tri-tyrosine (Tyr-Tyr), tetra-tyrosine (Tyr-Tyr) or a peptide comprising the foregoing.

6. The dietary supplement of claim 5, wherein said tyrosine is present as lysyl tyrosine or leucine-tyrosine.

7. The dietary supplement of claim 5, wherein said tyrosine is present in a dipeptide having the structure L-Tyr-X, wherein X is an amino acid.

8. A method for athletic performance or effort in a subject, comprising:

administering to the subject a composition comprising an effective amount of paratxanthine and tyrosine.

9. The method of claim 9, wherein administration of the paratxanthine and taurine produces a synergistic increase in athletic performance or effort in the subject relative to administration of the paratxanthine or taurine alone.

10. The method of claim 9, wherein the paratxanthine is provided in an amount of about 25mg to about 400mg, and wherein the tyrosine is provided in an amount of 100-150mg/kg of body weight of the subject.

11. The method of claim 11, wherein the subject experiences increased endurance or increased strength.

12. The method of claim 9, wherein the ratio of the amounts of hypoxanthine and tyrosine administered to the subject is about 1:10 to about 1:30.

13. The method of claim 9, wherein the composition is substantially free of caffeine.

14. A method of improving cognitive function in a subject comprising administering to the subject a composition comprising an effective amount of a parathyroid hormone and a tyrosine.

15. The method of claim 15, wherein 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, antegrade memory, retrograde memory, memory extraction, discrimination learning, decision making, suppression of reaction control, attention-oriented transfer, delayed reinforcement learning, reverse learning, temporal integration of voluntary behaviors, processing speed, reasoning, problem solving, and/or social cognition.

16. The method of claim 15, wherein the ratio of the amounts of hypoxanthine and tyrosine administered to the subject is about 1:10 to about 1:30.

17. The method of claim 15, wherein administering the composition to the subject enhances mood in the subject.

18. The method of claim 15, wherein the administration of the parathyroxypurine and tyrosine produces a synergistic enhancement of cognitive function in the subject relative to administration of the parathyroxypurine or tyrosine alone.

19. A method of enhancing energy or mood in a subject comprising administering to a subject a composition comprising an effective amount of paratxanthine and taurine, wherein the amount of paratxanthine administered to the subject is from about 25mg to about 800mg, and wherein the amount of taurine administered to the subject is from about 100mg to about 6000mg, and wherein the administration of paratxanthine and taurine produces a synergistic enhancement of energy and/or mood in the subject relative to the administration of paratxanthine or taurine alone.