CN118632697A

CN118632697A - Bioactive compositions and methods of use thereof

Info

Publication number: CN118632697A
Application number: CN202280063161.8A
Authority: CN
Inventors: R·耶格尔; M·普尔普拉; S·韦尔斯; K·廖
Original assignee: Nanjing Niubang Biotechnology Co ltd
Current assignee: Nanjing Niubang Biotechnology Co ltd
Priority date: 2021-07-27
Filing date: 2022-07-27
Publication date: 2024-09-10

Abstract

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

Description

Bioactive compositions and methods of use thereof

Cross Reference to Related Applications

The present application claims priority from U.S. c. ≡119 (e) for U.S. provisional application No. 63/203,644 and U.S. provisional application No. 63/226,057, filed on 7.27 days 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 7.27 days 2021 and entitled "COMBINATION OF PARAXANTHINE AND TAURINE-BASED BIOACTIVE COMPOSITION AND METHOD OF USE THEREOF", each of which is incorporated herein by reference in its entirety.

Technical Field

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

Background

Caffeine is a bitter white crystalline purine, a methylxanthine alkaloid, and is chemically related to 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 to protect them from predatory insects and prevent germination of nearby seeds. The best known source of caffeine is coffee beans, the misname of coffee plant seeds.

The concentration of caffeine in the coffee beverage may be quite variable. One cup of standard coffee is often assumed to provide 100mg caffeine, but recent analysis of 14 different fine coffee products purchased at U.S. coffee shops has found that the amount of caffeine in 8oz (240 ml) brewed coffee ranges from 72-130mg (McCusker, r.r., goldberger, b.a. and Cone, e.j.2003.caffeine content of specialty blends.j.analog.toolface, 27:520-522.). Caffeine in espresso coffee ranges from 58-76mg in a single serving. Interestingly, the caffeine content of the same type of coffee purchased from the same store on six separate days varied from 130 to 282mg per 8-oz serving. Many individuals experience sleep, anxiety and/or stress problems with caffeine, which can be exacerbated by unexpectedly high doses.

Thus, 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 chemical compounds and mixtures thereof that can be used to provide various benefits as a function of concentration, thus requiring the production of less material.

Disclosure of Invention

Disclosed herein are compositions comprising paratxanthine and tyrosine and/or taurine and methods of use thereof. In certain aspects, the paratxanthine and the 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), a co-crystallized product of glyceride, propylene glycol, lauroyl polyethylene glycol, a lauroyl polyethylene glycol derivative, piperine (bioperine), Piperine, black pepper, bergamotin, dihydroxybergamotin (CYP 3 A4), flavonoids (naringin, hesperidin, nobiletin, hesperetin, quercetin), pterostilbene, fisetin, phospholipid complexes (phytosomes), salicin, fish oils (omega-3 fatty acids and specific small lipid pro-inflammatory resolution epoxide derivatives), oxy lipids, acid cherries, krill oil, astaxanthin, proteolytic enzymes, glucosamine sulphate, chondroitin sulphate, 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, Chilli (cayenne), raspberry ketone, myrrh (guggul), green tea, guarana (guarana), cola, beta-phenylethylamine, acacia (Acacia rigidula), forskolin (coleus forskohlii (Coleus forskohlli)), theophylline, synephrine, yohimbine, rhodiola rosea, withania, ginseng, ginkgo biloba, siberian ginseng, astragalus, licorice, green tea, ganoderma lucidum, dehydroepiandrosterone (DHEA), pregnenolone, N-acetyl tyrosine, glucuronolactone, acetyl l-carnitine, 5-hydroxytryptophan, tryptophan, phenethylamine, twisted stevia rebaudiana (Sceletium tortuosum) (and dendrine alkaloids), dendrobe species (Dendrobium sp.), acacia, PQQ (pyrroloquinoline quinone), ubiquinone (01), nicotinamide riboside, pinamitraz, huperzine a (Huperzia serrata), levodopa, mucuna pruriens (Mucuna pruriens) and forskolin (coleus forskohlii), 2- (dimethylamino) ethanol (DMAE), huperzine a (Chinese clubmoss) or Huperzia serrata, DMAE bitartrate, ornithine, citrulline, pyruvate, acanthopanax (Eleutherococcus senticosus), D-ribose, whey protein, trimethylglycine, arginine, HMB (beta-hydroxy beta-methylbutyric acid), milk protein, schisandra chinensis (SCHISANDRA CHINENSIS), leucine, betalain (Betalains), leucine (Leucic Acid), L-carnitine, sodium bicarbonate, arachidonic acid, beta-alanine, brassinosteroids, alanylglutamine, deer grass (Rhaponticum carthamoides), and pharmaceutical compositions containing the same, casein, ecdysteroids, creatine, branched amino acids, beetroot, coffee, nitrate, korean ginseng (Panax ginseng), clenbuterol, alpha-GPC, valine, colostrum, conyza tannery (Trichopus zeylanicus), withania somnifera, terminalia arjuna (TERMINALIA ARJUNA), egg, ursolic acid, isoleucine, medium chain triglycerides, glutamine, zinc, vitamin D, maca (maca), schisandra (Schizandra), nicotinamide Mononucleotide (NMN), exogenous ketone, ergothioneine, and pharmaceutical compositions, Berberine, dihydroberberine and combinations thereof.

In certain embodiments, the composition comprises a combination of a homolog of paratxanthine and tyrosine, or a combination of a paratxanthine and tyrosine analog. In an exemplary embodiment, 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. In further embodiments, the tyrosine is present in polymerized form, and wherein the polymerized form is dityrosine (Tyr-Tyr), trityrosine (Tyr-Tyr), tetratyrosine (Tyr-Tyr), or a peptide comprising the foregoing. In a further embodiment, tyrosine is present as lysyl tyrosine or leucine-tyrosine. In an even further embodiment, tyrosine is present in a dipeptide having the structure L-Tyr-X, wherein X is an amino acid.

Further disclosed herein are methods for athletic performance or effort in a subject by administering to the subject a composition comprising an effective amount of a hypoxanthine and a tyrosine. In certain embodiments, administration of the parathyroxyxanthine and taurine results in a synergistic increase in athletic performance or effort in a subject relative to administration of the paratuanine or taurine alone. In certain implementations, 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. According to certain embodiments, the subject experiences increased endurance or increased strength.

In certain embodiments, the ratio of the amounts of hypoxanthine and tyrosine administered to a subject is about 1:10 to about 1:30. In a further embodiment, the ratio of the amounts of paratxanthine and tyrosine administered to a subject is from about 1:10 to about 1:10.

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

Further disclosed herein are methods of improving cognitive function in a subject comprising administering to the subject a composition comprising an effective amount of a parathyroid hormone. In certain embodiments, improved cognitive function in a subject 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. In certain embodiments, administration of the composition to a subject enhances mood in the subject. In further embodiments, administration of the parathyroxypurine and tyrosine results in a synergistic enhancement of cognitive function in the subject relative to administration of the parathyroxypurine or tyrosine alone.

Further disclosed herein are methods of enhancing energy or mood in a subject comprising administering to the 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.

While various embodiments are disclosed, still 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 realized, the disclosed compositions, systems and methods are capable of 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 in nature and not as restrictive.

Drawings

Fig. 1 shows exemplary data demonstrating the effect of certain disclosed compositions on forelimb strength in mice.

Detailed Description

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.

Ranges may be expressed herein as from "about" one particular value, and/or to "about" another particular value. When such a range is expressed, a further aspect includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about," it will be understood that the particular value forms a further aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also to be understood that a plurality of values are disclosed herein, and that each value is also disclosed herein as "about" that particular value, in addition to the value itself. For example, if the value "10" is disclosed, then "about 10" is also disclosed. It should also be understood that each unit between two particular units is also disclosed. For example, if 10 and 15 are disclosed, 11, 12, 13 and 14 are also disclosed.

As used herein, the term "subject" refers to a target, such as an animal, to which it is administered. Thus, the subject of the methods disclosed herein can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig, or rodent. The term does not indicate a particular age or gender. Thus, adult and neonatal subjects, whether male or female, are contemplated as well as fetuses. In one aspect, the subject is a mammal. A patient refers to a subject suffering from a disease or disorder. As used herein, the term "treatment" refers to the medical management of a patient, which is intended to cure, ameliorate, stabilize or prevent a disease, pathological condition or disorder. The term includes active treatment, i.e. treatment specific for the amelioration of a disease, pathological condition or disorder, and also includes causal treatment, i.e. treatment directed to the removal of the cause of the associated disease, pathological condition or disorder. In addition, the term also includes palliative treatment, i.e., treatment designed to alleviate symptoms rather than cure a disease, pathological condition, or disorder; prophylactic treatment, i.e., treatment intended to minimize or partially or completely inhibit the development of a related disease, pathological condition, or disorder; and supportive treatment, i.e., treatment for supplementing another specific therapy directed to an improvement in the associated disease, pathological condition, or disorder. 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 who 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) alleviating the disease, i.e., causing regression of the disease. In one aspect, the subject is a mammal, e.g., a primate, and in a further aspect, the subject is a human.

The term "subject" also includes domestic animals (e.g., cats, dogs, etc.), farm animals (e.g., cattle, horses, pigs, sheep, goats, etc.), and laboratory animals (e.g., mice, rabbits, rats, guinea pigs, drosophila, etc.).

As used herein, the terms "effective amount" and "effective amount" refer to an amount sufficient to achieve a desired result or to have an effect on an undesired 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 undesired symptom, but generally insufficient to cause unacceptable adverse side effects. The specific therapeutically effective dose level for any particular patient will depend on a variety of factors, including the condition to be treated and the severity of the condition; the specific composition used; age, weight, general health, sex, and diet of the patient; the time of application; route of administration; excretion rate of the specific compound employed; duration of treatment; drugs used in combination or simultaneously with the particular compound employed, and the like as is well known in the medical arts. For example, it is well within the skill of the art to initiate a dose of the compound at a level below that required to achieve the desired therapeutic effect and gradually increase the dose until the desired effect is achieved. If desired, the effective daily dose may be divided into multiple doses for administration purposes. Thus, a single dose composition may contain such amounts or their submultiples that make up the daily dose. In the case of any contraindications, the dose can be adjusted by the individual physician. The dosage may vary and may be administered as one or more doses per day for one or more days. Guidance can be found in the literature regarding the appropriate dosage of a given class of drug. In further aspects, the formulation may be in a "prophylactically effective amount"; i.e., an amount effective to prevent a disease or condition.

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

As used herein, the term "synergistically effective amounts" means and includes amounts of two or more active compounds which provide the synergistic effect defined above.

As used herein, the term "substantially" refers to a complete or near complete range or degree of action, characteristic, property, state, structure, item, or result. For example, an "substantially" enclosed object means that the object is completely enclosed or nearly completely enclosed. In some cases, the exact allowable degree of deviation from absolute completeness may depend on the particular context. In general, however, near completion will be such as to have the same overall result as absolute and overall. When used in a negative sense, the term "substantially" is equally applicable to a complete or nearly complete absence of an action, characteristic, property, state, structure, item, or result. For example, a composition that is substantially free of particles will be completely devoid of particles, or so almost completely devoid of particles, such that the effect will be the same as it is completely devoid of particles. In other words, a composition that is substantially free of ingredients or elements may actually still contain such items, so long as there is no measurable effect thereof.

As used herein, "cognitive function" refers to any advanced mental processes or brain states 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, antegrade memory, retrograde memory, memory extraction, discrimination learning, decision making, suppression of response control, attention-oriented transfer, delayed reinforcement learning, inverse learning, temporal integration of voluntary behaviors, and expression of interest in the surrounding environment and self-health, processing speed, reasoning, and problem solving and social cognition.

Composition and method for producing the same

Compositions comprising a combination of paratxanthine and tyrosine and related uses thereof are disclosed. Further disclosed herein are compositions comprising a combination of hypoxanthine and taurine and related uses thereof. The inosine may be produced synthetically or may be isolated from natural sources or by fermentation. The paratxanthines isolated from such sources may be purified to a purity of 95% or greater. Optionally, less purification can be used such that the combination of inosine comprises 50% or even less of the material. In some embodiments, it may be preferable to utilize isolated inosine from a natural source, which may include other homologs of the inosine typically found in the sources of the inosine.

In certain embodiments, the compositions are formulated such that the dose contains a range of about 1 to about 1000mg (e.g., 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 range or value therein) of the auxiliary xanthines.

Tyrosine has the chemical formula C ₉H₁₁NO₃ and has a molecular weight of 181.19. Tyrosine is a dietary amino acid. It is also synthesized by the body from phenylalanine or phenethylamine. In addition to its value as an energy substrate and in protein synthesis, it is a precursor to numerous biogenic amines and neurotransmitters. Tyrosine crosses the blood brain barrier and enters neurons where it becomes metabolized to catecholamine neurotransmitters. In certain embodiments, the source of tyrosine is a natural source. In a further embodiment, the tyrosine source is synthetic. In a further embodiment, the tyrosine is produced by fermentation.

According to a further embodiment, tyrosine is present as an ester (e.g., L-tyrosine ethyl ester, L-tyrosine methyl ester). In still further embodiments, the tyrosine is provided by a tyrosine derivative (e.g., N-acetyl-L-tyrosine and/or glycyl-L-tyrosine). In yet a further embodiment, the tyrosine derivative is present as an ester (e.g., N-acetyl-L-tyrosine ethyl ester and N-acetyl-L-tyrosine methyl ester). In a further embodiment, the tyrosine is present in polymerized 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 a further embodiment, tyrosine is present in a dipeptide having the structure L-Tyr-X, wherein X is an amino acid. In an exemplary implementation, the tyrosine is in the form of lysyl tyrosine or leucine-tyrosine.

Taurine has the chemical formula C ₂H₇NO₃ S and has a molecular weight of 125.14. Taurine is naturally derived from cysteine. Mammalian taurine synthesis occurs in the pancreas via the cysteine sulfinic acid pathway. In this pathway, cysteine is first oxidized to its sulfinic acid by a cysteine dioxygenase enzyme. The cysteine sulfinic acid is in turn decarboxylated by a cysteine sulfinic acid decarboxylase to form hypotaurine. The hypotaurine is enzymatically oxidized by a hypotaurine dehydrogenase to produce taurine. Synthetic taurine is obtained by ammonolysis of isethionic acid (2-hydroxyethanesulfonic acid), which in turn is obtained by reaction of ethylene oxide with aqueous sodium bisulphite. The direct process involves the reaction of aziridine with sulfurous acid. Taurine is essential for cardiovascular function and for 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 a further embodiment, the taurine is produced by fermentation.

In certain embodiments, taurine is present in an amount ranging from about 500mg to about 6000mg (e.g., about 500mg, about 1000mg, about 1,500mg, about 2,000mg, about 2,500mg, about 3,000mg, about 3,500mg, about 4,0000mg, about 4,500mg, about 5,000mg, about 5,500mg, or about 6000mg, etc., or any range or value therein).

In certain embodiments, a combination of hypoxanthine and tyrosine and/or taurine may 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 varying the combination of paratxanthine and tyrosine and/or the dosage of the chemical compound with which it is combined, various physiological effects can be selected. The composition may provide primarily a single benefit, or may provide multiple benefits simultaneously. in certain embodiments, the combination of hypoxanthine 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), 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, triterpenes, catechu, andrographis paniculata, baical skullcap root, agmatine sulfate, nettle, sea buckthorn, curcumin, four-edge powdery mildew, boswellia serrata, horseradish (mustard extract for tea tree oil), emu oil, arnica, mangrove (family Anacardiaceae), short flower gourd, ginger (ginger and gingerol/shogaol), cactus, caffeine, yohimbine, methyl synephrine, theobromine, tocopherol, theophylline, alpha-yohimbine, conjugated Linoleic Acid (CLA), octopamine, evodiamine, passion flower, red pepper, cayenne pepper, raspberry ketone, myrrh, green tea, guarana, cola fruit, beta-phenylethylamine, acacia, Forskolin (coleus forskohlii), theophylline, synephrine, yohimbine, rhodiola rosea, withania, ginseng, ginkgo biloba, siberian ginseng, astragalus, licorice, green tea, ganoderma lucidum, dehydroepiandrosterone (DHEA), pregnenolone, N-acetyl tyrosine, glucuronolactone, acetyl l-carnitine, 5-hydroxytryptophan, tryptophan, phenethylamine, twisted stevia rebaudiana (and pinocembrin alkaloids), dendrobium species, acacia, PQQ (pyrroloquinoline quinone), ubiquinone (01), nicotinamide riboside, pilocarpine, huperzine a (huperzia serrata, levodopa, mucuna, 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, kava, kanna, huperzine a, ketone, maca, ginseng, kava, rhodiola rosea, theanine, and combinations thereof.

In certain embodiments, the paratxanthine and the tyrosine are present in about equal amounts. In these embodiments, the combination weight of the combination of the inosine and the tyrosine in the composition is about 50% of the weight of the composition on a w/v basis. In certain further embodiments, the range may be at least 10% to 90% of paratxanthine and 90% to 10% of tyrosine, respectively.

In a further embodiment, the hypoxanthine and tyrosine are present in a ratio of 1:4 to about 1:30. In yet a further embodiment, the hypoxanthine 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 dose ranging from about 100-150mg/kg of body weight of the subject.

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

In certain embodiments, the compositions are formulated such that the dose contains tyrosine in the range of about 500 to about 13,500mg (e.g., about 500mg, about 1000mg, about 1,500mg, about 2,000mg, about 2,500mg, about 3,000mg, about 3,500mg, about 4,0000mg, about 4,500mg, about 5,000mg, about 7,500mg, 10,000, about 13,500mg, etc., or any range or value therein).

Depending on the subject to be treated and the route of administration, the compounds of the invention may be administered in different doses. Although the dose varies from subject to subject, suitable daily doses are within the range of about 1 to about 1000mg (e.g., 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 range or value therein)/subject administered in a single dose or multiple doses.

In certain embodiments, the compositions are formulated such that the dose contains a range of about 1 to about 1000mg (e.g., 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 range or values therein) of paratuanine, and a range of 400 to about 3000mg (e.g., about 400mg, about 450mg, about 500mg, about 550mg, about 600mg, about 650mg, about 700mg, about 750mg, about 800mg, about 850mg, about 900mg, about 950mg, about 1000mg, about 2000mg, about 3000mg, about 2500mg, or any range or values therein), or any range therein.

Nutritional supplement

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

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

Food product

The compositions of the present disclosure may take the form of a food product. The term "food" is used herein in a broad sense and covers both food and beverages for humans as well as food and beverages for animals (i.e. feed). Preferably, the food product is suitable and designed for human consumption.

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

When in the form of a food product, the composition may comprise 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 compositions of the present disclosure may take the form of one of the following: fruit juice; beverage comprising whey protein: health tea or herbal tea, cocoa, coffee, yogurt and/or drinkable yogurt, cheese, ice cream, dessert, candy, biscuit, cake mix or cake filling, snack, fruit filling, cake or doughnut coating, instant bakery filling cream, biscuit filling, instant bakery filling, low calorie filling, adult nutritional drink, acidified soybean/juice drink, nutritional or health bar, beverage powder, energy drink, sublingual, soft candy, calcium fortified soymilk or calcium fortified coffee drink.

Food ingredients

The compositions of the present disclosure may take the form of food ingredients and/or feed ingredients.

As used herein, the term "food ingredient" or "feed ingredient" includes compositions that are, or may be added to, functional foods or foods that are nutritional and/or health supplements for humans and animals.

The food ingredients may be in the form of liquids, suspensions or solids, depending on the use and/or mode of application and/or mode of administration.

Functional food

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

Accordingly, a functional food is a normal food having incorporated therein components or ingredients (such as those described herein) that impart specific functions-such as medical or physiological benefits-to the food other than a purely nutritional effect.

Although there is no legal definition of functional foods, most parties interested in this field agree that they are foods marketed as having specific health effects in addition to basic nutritional effects.

Some functional foods are nutraceuticals. As used herein, the term "nutraceutical" means a food that is not only capable of providing a nutritional effect and/or taste satisfaction, but also capable of delivering a therapeutic (or other beneficial) effect to a consumer. The nutraceutical spans the traditional dividing line between food and pharmaceuticals.

Medical food

The compositions of the present disclosure may take the form of a medical food. By "medical food" is meant a food formulated for consumption or administration with or without supervision by a physician and intended for specific meal management or conditions for which unique nutritional needs are established by medical assessment based on accepted scientific principles.

Application method

In certain embodiments, the paratxanthine may be combined with tyrosine and/or taurine, and in certain embodiments, one or more other chemical compounds (e.g., other active ingredients) to provide a variety of positive effects in a subject. By varying the dose of the hypoxanthine and/or chemical compound with which it is combined, various physiological effects can be selected. The composition may provide primarily a single benefit, or may provide multiple benefits simultaneously. Depending on the subject to be treated and the route of administration, the compounds of the invention may be administered in different doses. Although the dosage varies from subject to subject, suitable daily dosages are within the range of about 1 to about 14,500mg (e.g., 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, about 1000mg, about 1,500mg, about 2,000mg, about 2,500mg, about 3,000mg, about 3,500mg, about 4,0000mg, about 4,500mg, about 5,000mg, about 7,500mg, 10,000, about 13,500mg, about 14,000, about 14,500mg, or the like, or any range therein) administered in single or multiple doses.

In certain embodiments, the paratuanine and tyrosine and/or taurine may be administered to a subject as part of a single composition. In a further embodiment, the paratxanthine and the tyrosine and/or taurine are administered simultaneously or sequentially as separate compositions.

Advantageously, the compositions of the present disclosure may be administered in a single dose, e.g., one or less per day, or in total daily doses administered in divided doses of two, three or four times per day. In certain embodiments, the composition is administered in need thereof (e.g., when the subject is in need of enhanced energy, motor or cognitive performance, etc.).

Athletic performance

Further disclosed herein are methods for enhancing performance or effort in a subject comprising administering to the subject a composition disclosed herein. As used herein, the term "enhancing performance" is intended to mean any improvement in performance. The performance may be evaluated in any manner. Some enhancements are easily measured. For example, in a timed event, the improved time may evaluate the enhanced performance. Some performance enhancing properties may be judged subjectively by an athlete or performer or observer. In these cases, enhanced performance means that the performance is subjectively perceived as improved, amplified, faster, better, etc. In certain embodiments, the disclosed methods are used to enhance athletic performance. "athletic performance" refers to any professional or recreational activity in which a performer, such as an athlete, performs a physical action, such as running, swimming, golf, bowling, archery, football, baseball, basketball, soccer, hiking, cycling, dancing, and the like. In some cases, athletic performance is improved by endurance improvement in the subject. In other words, administration of the disclosed compositions improves the endurance level of the subject, thereby enhancing the athletic performance of the subject. In further embodiments, administration of the composition to a subject increases cognitive performance, which thereby improves motor performance.

In certain embodiments, the subject experiences an improvement in at least one of mood, energy, concentration, attention, or libido, or a reduction in at least one of anxiety, fatigue, effort perception, or pain perception after administration of the composition.

In further embodiments, the composition does not produce a dependency in the subject after continued administration to the subject and/or does not produce a withdrawal effect in the subject when continued use is stopped.

Further disclosed herein are methods of increasing exercise tolerance in a subject comprising administering to the subject a composition disclosed herein. In certain embodiments, the composition administered to the subject comprises parathyroid hormone. In an exemplary implementation, administration of the parathyroxypurine and tyrosine produces a synergistic increase in exercise tolerance in the subject relative to administration of the parathyroxypurine or 1-methylxanthine alone.

Further disclosed herein are methods of increasing exercise tolerance in a subject comprising administering to the subject a composition disclosed herein. In certain embodiments, the composition administered to the subject comprises paratuanine and taurine. In an exemplary implementation, administration of the parathyroxypurine and taurine produces a synergistic increase in exercise tolerance in the subject relative to administration of the parathyroxypurine or 1-methylxanthine alone.

According to a further embodiment, administration of the disclosed compositions to a subject increases the level of perceived effort of the subject. In an exemplary implementation, the subject experiences at least about 5% increase in energy. According to certain embodiments, the composition administered further comprises (in addition to the inosine and/or tyrosine and/or taurine) at least one ingredient selected from the group consisting of: l-theanine, phosphatidylcholine, alpha-GPC (L-alpha glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, bacopa monnieri (Bacopa Monnieri), phosphatidylserine, pilocarpine and cevimeline, lithospermum gracile (Amburana cearensis), ricepaper (Lippia sidoides), guarana (Paullinia cupana), dolichos (Plathymiscium floribundum), tetrahydrocurcumin and Solanum asperum and/or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2- (dimethylamino) ethanol (DMAE), DMAE bitartrate, huperzine A, matrine, methyl-large fruit caffeine, B12, sulbuthionine, magnolia officinalis, ketone, MCT, omega 3's, lutein, zeaxanthin and n-acetyl tyrosine, acetyl L-carnitine and/or combinations thereof.

In certain embodiments, the subject's level of perceived effort is increased by about 2% to about 50%. In further embodiments, the subject's level of perceived effort is increased by about 5% to about 30%. In still further embodiments, the subject's level of perceived effort is increased by about 10% to about 25%.

Muscle function

Further disclosed herein are methods for increasing muscle function in a subject by administering to the subject a composition disclosed herein. In certain aspects, disclosed herein are methods of promoting muscle growth by administering an effective amount of one or more of the compositions disclosed herein. In certain further aspects, administration of an effective amount of the disclosed compositions results in higher levels of myoprotein synthesis (MPS) in the subject. In a still further aspect, administration of an effective amount of the disclosed composition results in improved muscle proliferation in a subject.

In certain aspects, disclosed herein are methods of promoting muscle growth by administering an effective amount of one or more of the compositions disclosed herein. In certain further aspects, administration of an effective amount of the disclosed compositions results in higher levels of myoprotein synthesis (MPS) in the subject. In a still further aspect, administration of an effective amount of the disclosed composition results in improved muscle proliferation in a subject.

According to certain embodiments, the compositions disclosed herein may 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 the subject. In a still further aspect, the subject is a mammal. In a further aspect, the mammal is a human.

In certain aspects, administration of the disclosed compositions is effective to prevent or treat age-related muscle atrophy or sarcopenia. In a further aspect, administration of the disclosed compositions is effective in preventing or treating muscle atrophy associated with muscle fixation, such as occurs frequently in fractured bone casting (casting). In a further aspect, administration of the disclosed compositions is effective to prevent or treat muscle atrophy associated with diseases such as cancer (also referred to 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 a further aspect, the composition is administered in a prophylactically effective amount (e.g., to a subject at risk of developing sarcopenia, cachexia, or fixation-induced atrophy).

In certain aspects, the composition further comprises one or more additional active ingredients to further enhance muscle strength, size, and/or muscle function. In certain embodiments, the one or more additional active ingredients are amino acids. According to certain embodiments, the amino acid is selected from Branched Chain Amino Acids (BCAAs) including, but not limited to, isoleucine, leucine and valine. In a further embodiment, the amino acid is selected from the group consisting of essential amino acids including, but not limited to, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. In yet a further embodiment, the amino acid is selected from the group consisting of conditionally essential amino acids including, but not limited to, arginine, cysteine, glutamine, glycine, proline, ergothioneine and tyrosine. According to certain embodiments, the conditionally essential amino acid is tyrosine. In yet a further embodiment, the amino acid is selected from the group consisting of non-essential amino acids including, but not limited to, alanine, aspartic acid, asparagine, glutamic acid, serine, selenocysteine, and pyrrolysine. In a still further embodiment, the amino acid derivative is selected from the group consisting of creatine, carnitine, beta-alanine, taurine, beta-hydroxy beta-methylbutyrate L-arginine, omega-3 fatty acids, vitamin D, whey protein, BAIBA, and other protein extracts from animal, plant, or fermentation sources.

According to exemplary aspects of these embodiments, this may reduce fatigue, improve effort, increase mobility, and improve alertness. In further embodiments, administration of the disclosed compositions is cardioprotective. In further embodiments, administration of the disclosed compositions 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 a further aspect, muscle performance is enhanced by increasing intracellular calcium (e.g., via RyR activation).

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

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

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 compositions of the methods of enhancing cognitive function disclosed herein further comprise N-acetyl tyrosine, taurine, huperzine a, acetyl l-carnitine, CDP choline, alpha GPC, choline bitartrate, choline citrate, B12, caffeine, methyllarge fruit caffeine, matrine, paratoluine, theobromine, withania, rhodiola rosea, lutein, zeaxanthin, fish oil, creatine, ginseng, hericium erinaceum, niacin, cordyceps sinensis, theanine, B vitamins, GABA, sulbuthionine, vinpocetine, adenosine triphosphate, inositol, enhanced arginine silicate, nitrate, electrolytes, hesperidin and/or derivatives of portulaca.

In certain embodiments, the subject has experienced an age-related cognitive decline. In an exemplary implementation, administering the composition to the subject increases BDNF levels in the subject. According to certain embodiments, administering the composition to the subject increases Brain Derived Neurotrophic Factor (BDNF) levels in the subject. In an exemplary implementation, BDNF levels are increased by about 5% to about 40%. In further embodiments, BDNF levels are increased by at least about 15%. In further embodiments, administration of the composition to a subject increases other neurotrophic factors, such as Neuronal Growth Factor (NGF). In yet a further embodiment, administration of the composition to a subject increases mTOR levels in the CNS.

Therapeutic method

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 Disorder (ADHD), cognition 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 are methods for treating an mood disorder by administering to a subject in need thereof the compositions disclosed herein. In certain embodiments, the mood disorder is selected from clinical depression, post-partum depression or post-partum depression, perinatal depression, atypical depression, melancholy depression, psychotic major depression, tension depression, seasonal affective disorder, dysthymia, bipolar depression, depressive personality disorder, recurrent transient depression, mild depressive disorder, bipolar disorder or bipolar disorder, depression caused by chronic medical conditions, co-morbid depression, refractory depression, suicidal tendency, suicidal ideation or suicidal behavior. In some embodiments, the methods described herein provide therapeutic benefit to a subject suffering from depression (e.g., moderate or major depression). In some embodiments, the mood disorder is associated with a disease or disorder described herein.

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

Further disclosed herein are methods for treating anxiety in a subject in need thereof by administering to the subject in need thereof the compositions 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 collective term covering several different forms of abnormalities and morbid fear and anxiety.

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

In certain embodiments, the composition for use in a method of treating an mood disorder or anxiety disorder further comprises at least one ingredient selected from the group consisting of: l-theanine, phosphatidylcholine, alpha-GPC (L-alpha glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, bacopa monnieri, phosphatidylserine, pilocarpine and cevimeline, lithospermum gracile, libizia serrata, guarana, duohuaku bean, tetrahydrocurcumin and Solanum asperum and/or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2- (dimethylamino) ethanol (DMAE), DMAE bitartrate, magnolia officinalis, theanine, phosphatidylserine, willd's, rhodiola rosea, mucuna spinosa, twisted pine stevia, 5-HTP, tryptophan, saffron, vitamin D, SAMe, hericium erinaceum 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 the following: 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.

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 embodiments, the disclosed compositions are administered to a subject suffering from: narcolepsy, sleep apnea and shift work sleep disorders, insomnia, epilepsy, attention deficit disorder, attention deficit hyperactivity syndrome (ADHD), cognition 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 neuroprotective agents. In certain embodiments, administration of the disclosed compositions to a subject in need thereof is neuroprotective. In exemplary aspects of these embodiments, this neuroprotection is in a form that protects against dopaminergic cell death.

According to a further embodiment, the disclosed compositions are useful for the treatment of senile depression. In exemplary embodiments, the compositions are effective in treating subjects suffering from senile depression of primary, vascular or traumatic origin. And mental retardation in the elderly.

Administration of the disclosed compositions to a subject can 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, intra-aural administration, intra-cerebral administration, rectal administration, sublingual administration, intradermal administration, buccal administration and parenteral administration, including injections such as intravenous administration, intra-arterial administration, intramuscular administration and subcutaneous administration. Administration may be continuous or intermittent. In various aspects, the formulation may be administered therapeutically; i.e., administered to treat an existing disease or condition. In further aspects, the formulation may be administered prophylactically; i.e. for the prevention of diseases or conditions.

In another embodiment, a combination of hypoxanthine and tyrosine and/or taurine may be used at lower dosage levels and/or in combination with compounds that modulate or antagonize their activity. Such compositions may induce improved endurance performance, mood, vigor, lipolysis, energy expenditure, athletic performance and/or reduced appetite.

An advantage of using the disclosed compositions is that the likelihood of individuals developing resistance to chemical compositions is reduced. That is, the individual may not become desensitized to the induced effects. According to certain aspects, the disclosed compositions containing a combination of inosine and tyrosine and/or taurine have at least the following significant advantages over administration of compositions containing comparable doses of caffeine. The combination of paratuanine and tyrosine and/or taurine has substantially lower toxicity. The combination of paratxanthine and tyrosine has greater stability (e.g., does not lose potency over a period of time as caffeine does). Compositions containing a combination of paratuanines and tyrosine and/or taurine are more potent wake promoters (in certain embodiments, via adenosine receptor antagonism). Further, compositions containing a combination of paratxanthine and tyrosine and/or taurine enhance striatal dopaminergic tone. Still further, the combination of paratxanthine and tyrosine and/or taurine does not produce sleep rebound. Further, the combination of paratxanthine and tyrosine and/or taurine does not produce a withdrawal effect that frequently occurs with respect to caffeine after cessation of use. Still further, the combination of paratuanine and tyrosine and/or taurine does not enhance anxiety. Still further, the combination of paratxanthine and tyrosine and/or taurine has a less bitter taste than caffeine. Even further, the combination of paratxanthine and tyrosine and/or taurine is more effective than caffeine for a larger portion of the population. In another embodiment, a combination of hypoxanthine and tyrosine and/or taurine may be used at higher dosage levels and/or with synergistic compounds.

These compositions may increase basal/resting metabolic rate, increase thermogenesis, decrease appetite, enhance cognitive performance, increase alpha wave brain activity, and/or induce euphoria in an individual. Without being bound by theory, the inventors believe that at higher dose levels, compositions containing a combination of paratxanthine and tyrosine and/or taurine may be noradrenergic and dopaminergic, and may exhibit increased adenosine receptor inhibition.

In another embodiment, the paratxanthine and tyrosine and/or taurine are combined with ephedrine, caffeine, salicylic acid, and the like. The foregoing combinations may produce synergistic effects with the stimulating effects of the combination of paratxanthine and tyrosine. For example, in certain embodiments, paratxanthine and tyrosine may be combined with a much smaller amount of caffeine in order to modulate the hyperstimulative effects of caffeine, thereby stabilizing heart rate and other metabolic activities. That is, a combination of paratxanthine and tyrosine and/or taurine and caffeine may result in a composition that imparts increased concentration and effort induced by caffeine, but without higher heart rate and blood pressure due to the effects of caffeine that are modulated by the combination of paratxanthine and tyrosine and/or taurine. Thus, the combination may lead to enhanced consciousness and calm without stress that caffeine may cause.

In another embodiment, a combination of paratxanthine and tyrosine may 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. Topical agents containing a combination of paratuanine and tyrosine and/or taurine may also be used to promote localized loss of menstrual fat. Such compositions may also be used in creams or lotions to promote localized enhanced metabolism and/or enhanced heat production.

According to further embodiments, the paratxanthine and the tyrosine may be combined with one or more analgesic and/or anti-inflammatory agents. In an exemplary implementation, the combination of hypoxanthine and tyrosine and/or taurine is as follows: ibuprofen, salicylic acid, anti-inflammatory agents, salicin, fish oil (omega-3 fatty acids and specific small lipid pro-inflammatory resolution derivatives), acerola, krill oil, astaxanthin, proteolytic enzymes, glucosamine sulfate, chondroitin sulfate, MSM (methylsulfonylmethane), SAMe (S-adenosylmethionine), ASU (avocado soybean unsaponifiable fraction), cetyl myristate, falcate dolichos and/or triterpenes.

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

In certain embodiments, the composition comprises a ratio of about 1:5 of hypoxanthine and tyrosine. In certain embodiments, the amount of paratxanthine provided is from about 2mg to about 800mg, and the amount of tyrosine provided is from about 500mg to about 2000mg.

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

In another embodiment, a combination of paratxanthine and tyrosine and/or taurine is combined with one or more bioavailability enhancers. In exemplary embodiments, bioavailability enhancers include, but are not limited to: piperine, black pepper, bergamotin (CYP 3A4 inhibitor), flavonoids (including hesperidin, naringin, hesperetin, quercetin and nobiletin in both isolated and combined), pterostilbene, fisetin, nano-encapsulation, microcapsule encapsulation, liposomes and/or phospholipid complexes. The enhancer in combination with the combination of inosine and tyrosine may depend on what properties of the combination of inosine and tyrosine and/or taurine are desired for the particular application.

In another embodiment, a combination of paratxanthine and tyrosine may be administered using one or more delivery methods including, for example, transdermal patches and/or creams, powders that are readily mixed, intravenous methods, capsules, tablets, liquids (including liquids for mixing with other beverages), soft capsules, injectable forms, and/or cosmetic applications, including soaps, emulsions, and shampoos. The anti-inflammatory properties of the combination of paratxanthine and tyrosine may be desirable for various topical applications.

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

1. a composition comprising paratxanthine and tyrosine.

2. The composition of claim 1, further comprising one or more 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), 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 (_ω -3 fatty acids and specific small lipid pro-inflammatory resolution epoxide derivatives), oxy lipids, sour cherries, krill oil, astaxanthin, proteolytic enzymes, glucosamine sulfate, chondroitin sulfate, MSM (methylsulfonylmethane), and combinations thereof SAMe (S-adenosylmethionine), ASU (avocado soybean unsaponifiable fraction), cetyl myristate, falcate dolichos, triterpenes, catechu, andrographis paniculata, baikal skullcap root, agmatine sulfate, nettle, seabuckthorn, curcumin, erysiphe gracilis, mastic, horseradish (mustard extract for tea tree oil), emu oil, arnica, mangrove (anaceae), short-flowered cucurbit, ginger (ginger and gingerol/shogaol), cactus, caffeine, yohimbine, methyl synephrine, theobromine, flavonoid, tocopherol, theophylline, alpha-yohimbine, conjugated Linoleic Acid (CLA), octopamine, evodiamine, Passion flower, red pepper, cayenne pepper, raspberry ketone, commiphora mukul, green tea, guarana, cola, beta-phenylethylamine, acacia, forskolin (coleus forskohlii), theophylline, synephrine, yohimbine, rhodiola rosea, littoral, ginseng, ginkgo biloba, siberian ginseng, astragalus, licorice, green tea, ganoderma lucidum, dehydroepiandrosterone (DHEA), pregnenolone, N-acetyl, glucuronolactone, acetyl l-carnitine, 5-hydroxytryptophan, tryptophan, phenethylamine, twisted stevia rebaudiana (and dendrine alkaloid), dendrobe species, acacia, PQQ (pyrroloquinoline quinone), ubiquinone (01), nicotinamide riboside, Pekamion, huperzine A (Chinese huperzia or Huperzia serrata, levodopa, 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-methylbutyric acid), lactoprotein, schisandra chinensis, leucine, betalain, leucine, L-carnitine, sodium bicarbonate, arachidonic acid, beta-alanine, brassinosteroids, alanyl glutamine, deer grass, casein, ecdysteroids, creatine, branched amino acids, betaines, Coffee, nitrate, korean ginseng, clenbuterol, alpha-GPC, valine, colostrum, ceylon hairtail, withania somnifera, apocynum arvense, egg, ursolic acid, isoleucine, medium chain triglycerides, glutamine, zinc, vitamin D, maca, schisandra, nicotinamide Mononucleotide (NMN), exogenous ketone, ergothioneine, berberine, dihydroberberine, and combinations thereof.

3. The composition of claim 1, further comprising a combination of a homolog of paratxanthine and tyrosine or a combination of a paratxanthine and tyrosine analog.

4. The composition of claim 3, wherein the combination of paratxanthine homologues or analogues is selected from the group consisting of caffeine, 1-methylxanthine, a combination of paratxanthine and 7-methylxanthine, paratxanthine, theobromine, theophylline, dactyline, methyldactylicapnine, and combinations thereof.

5. The composition of claim 4, wherein the paratxanthine homolog or analog is caffeine.

6. The composition of claim 5, wherein the effective dose of caffeine is lower than the effective dose of caffeine in a composition that does not contain a combination of paratxanthine and tyrosine.

7. The composition 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.

8. The composition of claim 1 wherein the tyrosine is present in polymerized form.

9. The composition of claim 8, wherein the tyrosine is present as dityrosine (Tyr-Tyr), trityrosine (Tyr-Tyr-Tyr), tetratyrosine (Tyr-Tyr-Tyr-Tyr) or a peptide comprising the foregoing.

10. The composition of claim 8, wherein the tyrosine is present as lysyl tyrosine or leucine-tyrosine.

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

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

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

14. A composition comprising paratxanthine and taurine.

15. The composition of claim 14, further comprising one or more 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), 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, triterpenes, catechu, andrographis paniculata, baical skullcap root, agmatine sulfate, nettle, sea buckthorn, curcumin, four-edge powdery mildew vine, boswellia serrata, horseradish (mustard extract for tea tree oil), emu oil, arnica, mangrove (family Anacardiaceae), short flower gourd, ginger (ginger and gingerol/shogaol), cactus, caffeine, yohimbine, methyl synephrine, theobromine, flavonoid, tocopherol, theophylline, alpha-yohimbine, conjugated Linoleic Acid (CLA), octopamine, evodiamine, passion flower, red pepper, cayenne pepper, raspberry ketone, indian myrrh, green tea, guarana, cola fruit, beta-phenethylamine, acacia, forskolin (coleus forskohlii), theophylline, synephrine, yohimbine, rhodiola rosea, withania, ginseng, ginkgo biloba, siberian ginseng, astragalus, licorice, green tea, ganoderma lucidum, dehydroepiandrosterone (DHEA), pregnenolone, N-acetyl tyrosine, glucuronolactone, acetyl l-carnitine, 5-hydroxytryptophan, tryptophan, phenethylamine, twisted stevia rebaudiana (and pinasterine alkaloids), dendrobe species, acacia, PQQ (pyrroloquinoline quinone), ubiquinone (01), nicotinamide riboside, pilocarpine, huperzine A (Chinese lycopodium or huperzia, levodopa, mucuna pruriens and forskolin (coleus forskohlii), 2- (dimethylamino) ethanol (DMAE), DMAE bitartrate, ornithine, citrulline, pyruvate, radix Acanthopanacis Senticosi, D-ribose, whey protein trimethylglycine, arginine, HMB (beta-hydroxy beta-methylbutyric acid), milk protein, shizandra berry, leucine, betalain, leucine, L-carnitine sodium bicarbonate, arachidonic acid, beta-alanine, rape steroid, alanyl glutamine, deer grass, casein, ecdysteroids, creatine, branched chain amino acids, beet root, coffee, nitrate, korean ginseng, clenbuterol, alpha-GPC, valine, colostrum, inonotus cassiae, kandelia candel, Arjune, egg, ursolic acid, isoleucine, medium chain triglycerides, glutamine, zinc, vitamin D, maca, schisandra, nicotinamide Mononucleotide (NMN), exogenous ketone, ergothioneine, berberine, dihydroberberine, and combinations thereof.

16. The composition of claims 14-15, wherein the paratxanthine and taurine are present in a ratio of about 1:5.

17. The composition of claims 14-16, further comprising a combination of a parathyroid hormone homologue and/or a parathyroid hormone analogue.

18. The composition of claim 17, wherein the combination of paratxanthine homologues or analogues is selected from the group consisting of caffeine, 1-methylxanthine, a combination of paratxanthine and 7-methylxanthine, paratxanthine, theobromine, theophylline, dactyline, methyldactylicapnine, and combinations thereof.

19. The composition of claim 18, wherein the paratxanthine homolog or analog is caffeine.

20. The composition of claim 19, wherein the effective dose of caffeine is lower than the effective dose of caffeine in a composition that does not contain a combination of paratxanthine and tyrosine.

21. A composition of any preceding claim, wherein the composition is a powder.

22. A composition of any preceding claim, wherein the composition is a dietary supplement and the supplement is a solid oral dosage form.

23. A composition of any of the preceding claims, wherein the composition is formulated for topical administration.

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

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

26. The method of claim 25, wherein the subject experiences an improvement in at least one of mood, energy, concentration, attention, or libido, or a reduction in at least one of anxiety, fatigue, effort perception, or pain perception after administration of the composition.

27. The method of claim 26, wherein the composition does not produce a dependency in the subject after continued administration to the subject and/or does not produce a withdrawal effect in the subject when continued use is stopped.

28. The method of claim 25, wherein the amount of paratxanthine provided is from about 50mg to about 400mg.

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

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

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

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

33. The method of claim 25, wherein the composition further comprises at least one ingredient selected from the group consisting of: l-theanine, phosphatidylcholine, alpha-GPC (L-alpha glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, bacopa monnieri, phosphatidylserine, pilocarpine and cevimeline, lithospermum gracile, libizia serrata, guarana, duohuaku bean, tetrahydrocurcumin and Solanum asperum and/or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2- (dimethylamino) ethanol (DMAE), DMAE bitartrate, magnolia officinalis, theanine, phosphatidylserine, willd's, rhodiola rosea, mucuna spinosa, pinus contortulaefolius, 5-HTP, tryptophan, saffron, vitamin D, SAMe, hericium erinaceum and huperzine A.

34. A method of increasing exercise tolerance in a subject comprising administering to the subject a composition of any one of claims 1-24.

35. The method of claim 34, wherein the composition is the composition of any one of claims 1-11, and wherein administration of the parathyroxypurine and tyrosine produces a synergistic increase in exercise tolerance in the subject relative to administration of the parathyroxypurine or tyrosine alone.

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

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

38. The method of claim 34, wherein the composition is the composition of any one of claims 12-18, and wherein administration of the parathyroxypurine and taurine produces a synergistic increase in exercise tolerance in the subject relative to administration of the parathyroxypurine or taurine alone.

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

40. The method of claim 39, wherein the condition is selected from the group consisting of narcolepsy, epilepsy, attention deficit disorder, attention Deficit Hyperactivity Disorder (ADHD), cognition 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 an mood disorder.

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

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

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

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

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

47. The method of claim 40, wherein the composition comprises the paratxanthine in an amount of about 2mg to about 800 mg.

48. The method of claim 39, wherein the composition further comprises at least one ingredient selected from the group consisting of: l-theanine, phosphatidylcholine, alpha-GPC (L-alpha glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, bacopa monnieri, phosphatidylserine, pilocarpine and cevimeline, lithospermum gracile, libizia serrata, guarana, duohuaku bean, tetrahydrocurcumin and Solanum asperum and/or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2- (dimethylamino) ethanol (DMAE), DMAE bitartrate, magnolia officinalis, theanine, phosphatidylserine, withania somnifera, rhodiola rosea, n-acetyl tyrosine, mucuna pruriens, twisted stevia rebaudiana, 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 claims 1-24.

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

51. A method of improving cognitive performance in a subject comprising administering a composition of any of claims 1-24.

52. The method of claim 51, 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.

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

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

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

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

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

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

59. The nutritional supplement of claim 55, further comprising one or more compounds selected from the group consisting of: isoleucine, leucine and valine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, creatine, arginine, cysteine, glutamine, glycine, proline, carnitine, beta-alanine, beta-hydroxy beta-methylbutyric acid, L-arginine, omega-3 fatty acids, vitamin D, whey proteins 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 claims 1-24.

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

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

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

64. The method of claim 60, wherein the composition is the composition of any one of claims 12-18, and wherein the administration of the parathyroxyxanthine and taurine produces a synergistic increase in muscle size in the subject relative to administration of the paratuanine 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 claims 1-24.

66. The method of claim 65, wherein the amount of paratxanthine administered is between about 25mg and about 800mg.

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

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

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

70. The method of claim 69, wherein the composition is the composition of any one of claims 1-11, and wherein the administration of the parathyroxypurine and tyrosine produces a synergistic increase in energy perception in the subject relative to administration of a comparable dose of parathyroxypurine or tyrosine alone.

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

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

73. The method of claim 69, wherein the composition is the composition of any one of claims 12-18, and wherein the administration of the parathyroxypurine and taurine produces a synergistic increase in energy perception in the subject relative to administration of a comparable dose of paratuanine or taurine alone.

74. The method of claim 65, wherein the composition further comprises at least one ingredient selected from the group consisting of: l-theanine, phosphatidylcholine, alpha-GPC (L-alpha glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, bacopa monnieri, phosphatidylserine, pilocarpine and cevimeline, lithospermum gracile, libizia serrata, guarana, duohuaku bean, tetrahydrocurcumin and Solanum asperum and/or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2- (dimethylamino) ethanol (DMAE), DMAE bitartrate, magnolia officinalis, theanine, phosphatidylserine, withania somnifera, rhodiola rosea, n-acetyl tyrosine, mucuna pruriens, twisted stevia rebaudiana, 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 claims 1-24.

77. The method of claim 75, wherein the amount of paratxanthine administered is between about 50mg and about 400mg.

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 an increase in endurance.

80. The method of claim 76, wherein the composition is the composition of any one of claims 1-11, and wherein administration of the composition to the subject produces a synergistic increase in athletic performance with administration of a comparable dose of either parathyroid xanthine or tyrosine alone.

81. The method of claim 76, wherein the composition is the composition of any one of claims 12-18, and wherein administration of the composition to the subject produces a synergistic increase in athletic performance compared to administration of a comparable dose of parathyroid xanthine or taurine alone.

82. The method of claim 76, wherein the composition further comprises at least one agent selected from the group consisting of: l-theanine, phosphatidylcholine, alpha-GPC (L-alpha glycerophosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, bacopa monnieri, phosphatidylserine, pilocarpine and cevimeline, lithospermum gracile, libizia serrata, guarana, duohangyang bean, tetrahydrocurcumin and Solanum asperum and/or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2- (dimethylamino) ethanol (DMAE), DMAE bitartrate, huperzine A, matrine, methyl-megacaffeine, B12, sulbuthionine, magnolia officinalis, ketone, MCT, omega 3's, lutein, zeaxanthin and n-acetyl tyrosine, acetyl-L-carnitine and/or combinations thereof.

Examples

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

Example 1

Parafurine plus tyrosine

Cognition, memory and learning

1.1. Method of

Behavioral studies were performed in mice by a pole-climbing test using Cook to check learning and memory ability.

32 Male Swiss Albino mice of 8 weeks old were kept in animal houses at 12:12 hours photoperiod, at constant temperature (22.+ -. 3 ℃) and constant humidity (30% -70%) using a standard laboratory diet (Purina 5L79, rats and mice 18% protein; PMI Nutrition International, brentwood, MO, USA). Distilled water was provided without limitation. All animal experiments were reviewed and approved by the Institutional animal ethics Committee (Institutional ANIMAL ETHICAL Committee) (IAEC) of RADIANT RESEARCH SERVICES pvt.ltd (Bangalore, india). All studies were conducted according to the guidelines of the committee for the purpose of controlling and supervising experiments with animals.

After one week of acclimation, animals were randomized into four groups per body weight (n=8 per group in each test) for oral treatment once daily at about the same time of day (±1 hour) for a total of 7 consecutive days: (1) vehicle control or (2) paratxanthine or (3) tyrosine or (4) tyrosine plus paratxanthine. The dose administered to mice was calculated using the equivalent dose (HED) for humans by the United states food and drug administration (US Food and Drug Administration), assuming a human weight of 60 kg. The following HEDs were used in this study: 100mg of ParafuanineIngenious Ingredients, l.p LEWISVILLE, TX, USA; mouse dose: 20.5mg/kg bw/day) or 500mg tyrosine (mouse dose: 102.75mg/kg bw/day), or 500mg tyrosine (mouse dose: 102.75mg/kg bw/day) plus 100mg of paratunguentumIngenious Ingredients, l.p LEWISVILLE, TX, USA; mouse dose: 20.5mg/kg bw/day). Test article formulations were prepared daily using 0.5% sodium carboxymethyl cellulose as vehicle. Administration was via oral gavage using a disposable polypropylene syringe with a sterilized stainless steel gavage tube. Food intake was monitored daily while water intake was unrestricted.

Climbing pole test of Cook

The mice were trained in such a way that the animals had to climb up the pole (no shock zone) within 30 seconds to avoid a shock. The shock was preceded by a beep lasting 15 seconds. The animals were trained to climb the pole (conditioned avoidance response) while the buzzer was sounding. Within a specified interval, 20 trials were given for each animal and averages were recorded that avoided shock and error. The trained animals were assayed by conditioned avoidance response.

1.3. Induction of amnesia

Amnesia was induced by injection with scopolamine. Scopolamine is an anticholinergic and an attractive amnestic agent for distinguishing the effects of candidate anti-amnestic drugs. Scopolamine is a non-selective postsynaptic muscarinic receptor blocker and can cause cognitive impairment in rodents and humans by reducing the effectiveness of ACH in the CNS in animals and humans. Scopolamine can induce significant deficits in cognitive performance at the time of behavioral testing, 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 deficit.

2. Results

Mice treated with paratxanthine showed reversal of scopolamine-induced amnesia and improved memory and learning. The combination of parathyroxypurine and tyrosine shows a synergistic effect over that of parathyroxypurine or tyrosine alone.

2.1. Supplement effect on the pole-climbing test of Cook

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

Example 2

Parafurine plus tyrosine

Sports and active nutrition, athletic performance, strength, energy, and emotion

1.1. Method of

After one week of acclimation, animals were randomized into four groups per body weight (n=8 per group in each test) for oral treatment once daily for approximately the same time (1 hour) per day for a total of 28 consecutive days: (1) vehicle control or (2) paratxanthine or (3) tyrosine or (4) tyrosine plus paratxanthine. The dose administered to mice was calculated using the equivalent dose (HED) for humans by the United states food and drug administration, assuming a human weight of 60 kg. The following HEDs were used in this study: 100mg of ParafuanineIngenious Ingredients, l.p LEWISVILLE, TX, USA; mouse dose: 20.5mg/kg bw/day) or 500mg tyrosine (mouse dose: 102.75mg/kg bw/day), or 500mg tyrosine (mouse dose: 102.75mg/kg bw/day) plus 100mg of paratunguentumIngenious Ingredients, l.p LEWISVILLE, TX, USA; mouse dose: 20.5mg/kg bw/day). Test article formulations were prepared daily using 0.5% sodium carboxymethyl cellulose as vehicle. Administration was via oral gavage using a disposable polypropylene syringe with a sterilized stainless steel gavage tube. Food intake was monitored daily while water intake was unrestricted.

1.2. Forelimb grip strength test

On day 0 and day 28, forelimb grip strength was measured by using a stainless steel mesh to evaluate muscle strength (Orchid Scientific & Innovative INDIA PVT LTD, india). Grip strength was measured one hour after treatment. Briefly, each mouse was first placed in the test chamber for ten minutes to acclimate to the environment. Each mouse was then placed on top of the grip dynamometer grid to allow the mouse to grasp the grid with all four paws. The mice were held by the base of the tail without pressing down on the mesh. The animals were then gently pulled back off the grid by pulling the tail along the grip measurement axis. The speed was slow enough to allow the mice to develop resistance to pull and once the mice released the grid, the fraction (gf) displayed on the screen of the grip measurement was recorded. Three independent experiments were performed for each animal and the average of the three experiments was calculated and recorded.

1.3. Exercise training

Training was completed in a swimming chamber at moderate room temperature for 15 minutes during the treatment period. During the treatment period, animals were acclimatized to the procedure 1 hour after dosing daily for 5 days of the week. On day 28 of the respective treatment, all animals were subjected to the forced swim test. Animals were forced to individually swim for 30 minutes at room temperature in glass jars having a height of 20cm, a diameter of 10cm and a depth of 15cm filled with fresh water. The parameter measured is the total time spent actively swimming (the total duration of time during which the animal swims throughout the experimental period).

2. Results

As shown in fig. 1, mice treated with hypoxanthine showed improved strength over the control. Tyrosine improves strength to a lesser extent, however, the combination of paratxanthine and tyrosine shows a synergistic effect over paratxanthine or tyrosine alone.

2.1. Supplement the effect of holding force on forelimbs

2.2. Supplement of effects on energy and emotion

Mice treated with hypoxanthine showed improved energy and emotion. The combination of parathyroid xanthine and tyrosine showed synergistic benefits over parathyroid xanthine and tyrosine alone.

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

Example 3

Parafuanine plus taurine

Energy and emotion

1.1. Method of

24 Male Swiss Albino mice of 8 weeks of age were kept in animal houses at 12:12 hours photoperiod, at constant temperature (22.+ -. 3 ℃) and constant humidity (30% -70%) using a standard laboratory diet (Purina 5L79, rats and mice 18% protein; PMI Nutrition International, brentwood, MO, USA). Distilled water was provided without limitation. All animal experiments were reviewed and approved by the Institutional animal ethics Committee (Institutional ANIMAL ETHICAL Committee) (IAEC) of RADIANT RESEARCH SERVICES pvt.ltd (Bangalore, india). All studies were conducted according to the guidelines of the committee for the purpose of controlling and supervising experiments with animals.

After one week of acclimation, animals were randomized into three groups per body weight (n=8 per group in each test) for oral treatment once daily for approximately the same time (1 hour) per day for a total of 28 consecutive days: (1) paratxanthine or (2) taurine or (3) taurine plus paratxanthine. The dose administered to mice was calculated using the equivalent dose (HED) for humans by the United states food and drug administration, assuming a human weight of 60 kg. The following HEDs were used in this study: 100mg of ParafuanineIngenious Ingredients, l.p LEWISVILLE, TX, USA; mouse dose: 20.5mg/kg bw/day) or 500mg taurine (mouse dose: 102.75mg/kg bw/day), or 500mg taurine (mouse dose: 102.75mg/kg bw/day) plus 100mg of paratunguentumIngenious Ingredients, l.p LEWISVILLE, TX, USA; mouse dose: 20.5mg/kg bw/day). Test article formulations were prepared daily using 0.5% sodium carboxymethyl cellulose as vehicle. Administration was via oral gavage using a disposable polypropylene syringe with a sterilized stainless steel gavage tube. Food intake was monitored daily while water intake was unrestricted.

1.2. Exercise training

Training was completed in a swimming chamber at moderate room temperature for 15 minutes during the treatment period. During the treatment period, animals were acclimatized to the procedure 1 hour after dosing daily for 5 days of the week. On day 28 of the respective treatment, all animals were subjected to the forced swim test. Animals were forced to individually swim for 30 minutes at room temperature in glass jars having a height of 20cm, a diameter of 10cm and a depth of 15cm filled with fresh water. The parameters measured were the total time spent actively swimming (the total duration of time the animal swims throughout the experimental period during which it was) and the duration of immobility (the total time the animal was immobile during which it was).

2. Results

Mice treated with a combination of paratuanines and taurine showed a synergistic effect over either paratuanine or taurine alone.

2.1. Supplement of effects on energy and emotion

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

The duration of immobility was synergistically shorter in the combination group of parathyroxypurine and taurine (21.25.+ -. 1.04 min) compared to taurine (21.50.+ -. 2.20 min) and parathyroxypurine (21.38.+ -. 1.92 min).

Claims

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.