• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    dietary supplement, and use of a composition. a human dietary supplement comprises theacrine and, optionally, other compounds that modulate the effects of theacrine. Uses for the theacrine-containing supplement include at least one improvement in mood, energy, focus, concentration or sex drive or a reduction of at least one in anxiety or fatigue.
    公开号:BR112016010422B1
    申请号:R112016010422-6
    申请日:2014-11-12
    公开日:2021-08-31
    发明作者:Hector L. Lopez；Shawn Wells；Tim N. Ziegenfuss
    申请人:Ortho-Nutra, Llc；
    IPC主号:
    专利说明:

    FIELD OF THE INVENTION
    [001] The present invention relates to systems and methods for using theacrine alone and in combination for use in providing physiological benefits. More particularly, the invention relates to theacrine and other natural compounds, whether synthetically produced or harvested from natural sources, and the use of these chemical compounds to provide physiological benefits, which may vary according to the concentration of theacrine and the presence of synergists and antagonists. BACKGROUND OF THE INVENTION
    [002] Tea is one of the most widely consumed products in the world. Tea and the different varieties of tea have been studied extensively. Many epidemiological and preclinical studies suggest that drinking tea may reduce the risk of cancer and cardiovascular disease. Teacrine, a caffeine-like alkaloid purine, is relatively rare and is only present in some tea varieties (Kucha tea, Camellia genus), the cupuaçu fruit, and other coffee and cocoa related plants (Coffea and Theobroma genera) , such as Coffea liberica, Coffea dewevrei, Coffea abeokutae and Theobroma grandiflorum.
    [003] 1,3,7,9-Tetramethyluric acid, commonly known as theacrine, was not studied until about 1975. However, it was known since about 1937, when it was detected in decaffeinated Camellia sinensis tea leaves , dried. At present, the tea variety Camellia assamica var. Kucha is the primary source of natural theacrine and produces the chemical in higher concentrations than other known plants. Interestingly, theacrine has not been detected at all in more traditional tea varieties. It is thought to be formed by methylation of caffeine and may be an intermediate in the production of liberin or other purines. Its natural function, if any, remains unknown. Theacrine has attracted attention only relatively recently, and often only as a secondary consideration when looking at other compounds. Some studies suggest that it may have beneficial qualities, such as serving as an antioxidant, effective anti-inflammatory, and may have anti-obesity properties.
    [004] In studies involving theacrine, the beneficial effects may be at least partially attributable to an assortment of purine alkaloids and phenolic compounds. The most common tea-related purine alkaloids include caffeine, theobromine, theophylline, and theacrine. The main phenolic compounds in tea are gallic acid and eight natural tea catechins, including (+)-catechin (C), (-)-epicatechin (EC), (+)-gallocatechin (GC), (-)-epigalocatechin (EGC), (-)-catechin gallate (CG), (-)-gallocatechin gallate (GCG), (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG).
    [005] Many different biological and physiological activities have been attributed to tea and its various components. However, only some of its components have been studied in depth. Caffeine is by far the most studied, and the most commonly used stimulant in tea. Theacrine appears to have an opposite effect, despite being very similar in terms of chemical structure. Recent experiments have shown that theacrine exhibits a variety of activities, some of which appear inconsistent.
    [006] In recent years, there has been a substantial shift in public opinion towards the use of natural chemical compounds for a variety of purposes rather than synthetic chemicals. For example, a wide variety of natural chemicals are now commonly used as sedatives, for example valerian root and chamomile, antidepressants, for example St John's Wort, stimulants, for example caffeine, and concentration, for example ginseng. In general, natural compounds can be easier to digest and interact with the body and can include minimal and less serious side effects.
    [007] Therefore, it is desirable to identify natural 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 a variety of benefits, which vary with concentration, thus requiring fewer materials to be produced or harvested. SUMMARY OF THE INVENTION
    [008] Therefore, the main objective of the present invention is to provide a chemical composition comprising theacrine, produced naturally or synthetically, and optionally other chemicals, including theacrine congeners or analogues, to provide a plurality of desirable effects. Theacrine analogues can include, but are not limited to, caffeine, methylcaffeine, theobromine, theophylline, liberin and methylliberal, and variants thereof. Other suitable active agents can include one or more ergogenic or nootropic compounds, such as CDP choline, alpha-GPC, choline bitartrate, St. John's Wort, sulbutyamine and the like.
    [009] Theacrine exhibits a wide variety of effects depending on dosage. The presence of other ingredients can also modulate their effects. It can be used to promote calm or focus and to relax, but it can also be used to improve energy and stamina. It can also serve as an antioxidant and an anti-inflammatory.
    [010] In one modality, theacrine can be used to modulate stimulants, to provide greater energy without increasing anxiety or nervousness. There may be variability between individuals, as described herein.
    [011] In another modality, theacrine can be used as a sedative or mild relaxant.
    [012] In another modality, theacrine can be used to promote weight loss, act as an antioxidant and as an anti-inflammatory. Theacrine can be used transdermally to ameliorate one or more of these effects.
    [013] In one embodiment, a dietary supplement comprising about 5 mg to about 850 mg of theacrine, natural or synthetic, is provided.
    [014] In another embodiment, a treatment method is provided to improve performance or physical energy in an individual. Said method involves providing the subject with a composition comprising about 5 mg to about 850 mg of theacrine, either natural or synthetic, wherein upon administration of the composition the subject experiences an improvement of at least one of mood, energy, focus, concentration or sexual desire or a reduction of at least one of anxiety or fatigue. In another embodiment, a second compound such as caffeine can also be administered in the composition.
    [015] Therefore, it is an object of the present invention to provide compositions including theacrine capable of imparting a plurality of positive effects.
    [016] It is another objective of the present invention to provide congeners, derivatives and iterations of theacrine and synthetic chemical equivalents of theacrine.
    [017] It is another objective of the present invention to provide agglomerated theacrine, teacrine salts, microencapsulated, liposomal or esterified theacrine.
    [018] It is another objective of the present invention to provide teacrine combined with glycerides, propylene glycol, polyethylene glycol (PEG), lauroyl macrogol, lauroyl macrogol derivatives and cocrystallization products of theacrine.
    [019] These and other objectives and advantages of the present invention will become evident from a reading of the enclosed descriptive report and appended claims. The most important characteristics of the invention have thus been outlined, very roughly, so that the detailed descriptive report below can be better understood, and so that the present contribution to the technique can be better understood. There are features of the invention that will be described below and that will constitute the subject matter of the claims appended hereto. BRIEF DESCRIPTION OF THE DRAWINGS
    [020] Figure 1 is a molecular diagram of theacrine according to the principles of the invention.
    [021] Figure 2 is a graph of trial results showing perceived energy on a VAS scale (0 to 10 cm) at 1, 2, and 3 hours after administration of teacrine or placebo.
    [022] Figure 3 is a graph of trial results showing fatigue perceived on a VAS scale (0 to 10 cm) at 0 minutes and 60 minutes after administration of teacrine or placebo.
    [023] Figure 4 is a graph of the results of a trial showing systolic blood pressure at various time intervals after administration of teacrine or placebo.
    [024] Figure 5 is a graph of the results of a trial showing diastolic blood pressure at various time intervals after administration of teacrine or placebo.
    [025] Figure 6 shows the results of a 7-day repeated dose study of 200 mg teacrine against baseline in: fatigue (0.64), anxiety (-0.59) and libido (0.71 ) at various intervals after dosing (at 0:00, 1:00, 4:00, 6:00; bars from left to right for each measured category).
    [026] Figure 7 shows the results of a 7-day repeated dose study of 200 mg teacrine relative to baseline in: energy (0.63), exercise motivation (0.58), and concentration ( 0.60) at various intervals after dosing (at 0:00, 1:00, 4:00, 6:00; bars from left to right for each measured category). DETAILED DESCRIPTION OF THE INVENTION
    [027] 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 arrangements of components set out in the following description or illustrated in the drawings. The invention may have other embodiments and may be practiced and carried out in various ways. Likewise, it is to be understood that the phraseology and terminology used herein are for the purpose of description and are not to be construed as limiting.
    [028] An invention is disclosed which relates to uses of theacrine, also known as 1,3,7,9-tetramethyluric acid, Temurine, Temorine, tetramethyluric acid, tetramethyl uric acid and 1,3,7,9-tetramethylpurine- 2,6,8-trione. Theacrine can be produced synthetically or it can be isolated from a natural source. Theacrine isolated from a natural source can be purified to 95% or more. Optionally, less purification can be used such that theacrine accounts for 50%, or even less, of the material. In some embodiments, it may be preferable to use theacrine isolated from a natural source which may include other theacrine congeners typically found in theacrine isolates.
    [029] In one embodiment, theacrine can be combined with other chemical compounds to provide a plurality of positive effects in a human or other animal. By changing the dosage of theacrine and/or the chemical compounds with which it is combined, various physiological effects can be selected. The compositions may primarily provide a single benefit, or they may provide multiple benefits simultaneously.
    [030] In another modality, theacrine can be used at lower dosage levels and/or in conjunction with compounds that modulate or antagonize its activity. Such compositions can induce an improved mood, increased energy, a reduction in fatigue, an increase in focus, increased concentration, increased mobility, decreased appetite, and increased stamina.
    [031] An advantage of using the invention may be the reduced probability that a person will develop a tolerance to chemical compositions in accordance with the principles of the invention. That is, a person may not be desensitized to the induced effects.
    [032] In another modality, theacrine can be used at higher dosage levels and/or with synergistic compounds. These compositions can increase a person's resting/basal metabolic rate, increase thermogenesis, decrease appetite, improve cognitive performance, increase alpha wave brain activity, and/or induce euphoria. Without being bound by theory, the inventors believe that at higher dosage levels, theacrine may be noradrenergic and dopaminergic, and may exhibit greater adenosine receptor inhibition.
    [033] In another embodiment of the invention, theacrine can be combined with ephedrine, caffeine, salicylic acid or the like. These can be used to modulate the more sedative effects of theacrine or, optionally, to interact synergistically with the more stimulating effects of theacrine. For example, theacrine can be combined with caffeine to modulate the excessive stimulatory effects of caffeine, thereby stabilizing heart rate and other metabolic activity. That is, a combination of theacrine and caffeine can result in a composition that confers increased focus and caffeine-induced energy, but without the higher heart rate and blood pressure due to the modulation of caffeine by theacrine. Thus, the combination can result in heightened states of awareness and calm without the stresses that caffeine can create.
    [034] Theacrine and caffeine given in combination have unexpected effects. In fact, it was unexpectedly found that a combination of theacrine and caffeine administered to human subjects results in increased levels of focus, concentration and energy as measured by the 100mm VAS scales, while also decreasing measures of anxiety, irritability or feelings of overstimulation. This decrease in anxiety, irritability, tension and/or feelings of overstimulation is reflected by patients in the 100 mm VAS standardized for durations of 30 minutes, 60 minutes, 120 minutes and 180 minutes compared to administration of caffeine alone. The combination also exhibits a prolonged duration of action with increased energy, focus and/or concentration compared to caffeine or theacrine alone.
    [035] In addition, theacrine also has unexpected effects on the development of tolerance and addiction to caffeine. In a study of fourteen days of repeated teacrine and caffeine administration, subjects were found to maintain higher psychometric indices of energy, focus, concentration, exercise motivation, motivation to perform and complete tasks, and better mood on Day 14 compared with caffeine alone, and absolute levels of energy and motivation were higher than with theacrine alone. Those taking theacrine alone still maintained high subjective energy, focus, concentration, exercise motivation, motivation to perform and finish tasks, sexual desire and better mood with less anxiety compared to Day 1. Individuals taking caffeine alone saw the energy, focus and concentration levels decreased by Day 5 of the study and had increased anxiety scores throughout the study.
    [036] In another embodiment of the invention, theacrine can be combined with one or more bioavailability enhancers, including, for example, bioperine, piperine, black pepper, bergamotin, dihydroxybergamotine (CYP3A4 inhibitors), flavonoids (including hesperidin, naringin, mandarin, quercetin and nobiletin both in isolation and in combination), pterostilbenes, fisetin, nanoencapsulation, microencapsulation, liposomes and/or phytosomes. Enhancers that are combined with theacrine may depend on the qualities of theacrine that are desired for a particular use.
    [037] In another embodiment of the invention, theacrine can be introduced using one or more methods of administration, including, for example, transdermal patches and/or creams, ready-to-mix powders, intravenous methods, capsules, tablets, liquids (including liquids for mix with other beverages), smooth gels, serving format, and/or cosmetic applications including soaps, lotions and shampoos. The anti-inflammatory qualities of theacrine may be desired for a variety of topical applications.
    [038] In another embodiment of the invention, theacrine can be used to provide sports performance enhancers that can reduce fatigue, improve mobility and improve alertness.
    [039] In another embodiment of the invention, theacrine can be used as a topical agent for incorporation into body creams or lotions to produce a cream or lotion for skin lightening, skin firming, and/or skin elasticity improvement. A topical teacrine agent can also be used to promote localized transdermal fat loss. Theacrine can also be used in a cream or lotion to promote improved localized metabolism and/or improved thermogenesis.
    [040] In another embodiment of the invention, theacrine can be combined with one or more of an analgesic, for example ibuprofen or salicylic acid, anti-inflammatory agents, salicin, fish oil (omega-3 fatty acids and pro-resolution derivatives of small, specialized lipids), sour cherry, krill oil, astaxanthin, proteolytic enzymes, glucosamine sulfate, chondroitin sulfate, MSM (methylsulfonylmethane), SAMe (S-adenosylmethionine), ASU (soy avocado unsaponifiable fraction), myristoleate of cetyl, Dolichos falcatus and/or triterpenoids.
    [041] Theacrine itself may reduce inflammation biomarkers in humans in response to factors causing acute inflammatory stress (eg, strenuous exercise) or chronic consumption. Teacrine has been shown to decrease C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6) and TNF-alpha.
    [042] In another embodiment of the invention, theacrine can be combined with extracts of one or more of Acacia catechu, Andrographis paniculata, Scutalleria baicalensis, agmatine sulfate, Nettle, Maritime Hawthorn, curcumin, Cissus Quadrilangularis, Boswellia Serrata, Wasabia japonica ( wasabi extract for Tea Tree Oil), Emu Oil, Arnica, Mangifera indica L. (Anacardiaceae), Lagenaria breviflora, and/or Zingiber officinale (ginger & gingeroles/sogaoles). Such a combination can be used in, for example, methods of increasing and improving pain modulation, and controlling the inflammatory response.
    [043] In another embodiment of the invention, theacrine may be combined with one or more metabolic enhancers including hoodia gordonii, caffeine, yohimbine, synephrine, theobromine, flavonoids, flavanone glycosides such as naringin and hesperidin, tocopherols, theophylline, alpha-yohimbine , conjugated linoleic acid (CLA), octopamine, evodiamine, grenadilla, red pepper, cayenne pepper, raspberry ketone, guggul, green tea, guarana, kola nut, any beta-phenethylamines, Acacia rigidula, and/or forskolin (Coleus forskohlli). Such a combination can be used, for example, in methods of improving 1) thermogenesis/metabolism of fat and carbohydrates; 2) fat loss, weight management and body composition improvement (loss of body fat, while maintaining or saving lean body mass/non-fat mass/muscle); and/or 3) appetite control/ appetite modulation.
    [044] Combinations of theacrine and, for example, caffeine, theobromine, or flavanone glycosides such as naringin or hesperidin, after administration to individuals exhibit lower VAS 100mm scores of perceived physical exertion with exercise compared to the ingredients alone. Theobromine is used by some for improved breathing or a subjective feeling of improved breathing, but it is also known to increase feelings of anxiety, tension and a high heart rate in some individuals. A combination of theobromine and theacrine retains the beneficial effects while reducing the unwanted effects of anxiety, tension and/or high heart rate.
    [045] In another embodiment of the invention, theacrine may be combined with anti-fatigue, focusing and/or energy enhancing ingredients including caffeine, theobromine, theophylline, synephrine, yohimbine, rhodiola, ashwagandha, ginseng, ginkgo biloba, Siberian ginseng, Astragalus , licorice, green tea, reishi, dehydroepiandrosterone (DHEA), pregnenolone, tyrosine, N-acetyl-tyrosine, glucuronolactone, taurine, choline, CDP-choline, alpha-GPC, acetyl-L-carnitine, 5-hydroxytryptophan, tryptophan, any beta-phenethylamines, Sceletium tortuosum (and Mesembrine alkaloids), Dendrobium sp., Acacia rigidula, PQQ (Piroloquinoline quinone), Ubiquinone(ol), nicotinamide riboside, picamilon, Huperzine A (Chinese lycopodium) or Huperdozia serrata, Mucuna pruriens, forskolin (Coleus forskohlli). Such a combination can be used, for example, in methods of improving cognitive function, including focus, concentration, sustained attention, working memory, choice and non-choice reaction time, executive function, verbal and non-verbal learning, visual memory. - spatial and verbal fluency.
    [046] In another embodiment, theacrine can be combined with a nutritional cholinergic ingredient such as 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, choline bitartrate, alpha-GPC (alpha-glycerophosphorylcholine), Huperzine A, CDP choline, or combinations thereof. One of skill in the art will recognize that these are only examples of cholinergic ingredients and that other cholinergic ingredients not listed are also contemplated by the present invention. The combination of a nutritional cholinergic ingredient with theacrine can result in a synergistic effect of increased psychometric measurements for attention, focus and concentration beyond either theacrine alone or the cholinergic ingredient alone.
    [047] In another embodiment, any of the above combinations can be used with an isomer, congener, derivative and/or metabolite of theacrine such as, for example, liberin or methyl-libertine. Other suitable examples include methylated theacrine, theacrine nitrate salts, oxidized theacrine, reduced theacrine and/or theacrine salts. Agglomerated theacrine, microencapsulated theacrine, liposomal theacrine, esterified theacrine, theacrine glycerides, and mixtures of theacrine with propylene glycol, lauroyl macrogol, polyethylene glycol, theacrine derivatives, and/or theacrine cocrystallization products may also be used in accordance with the principles of the invention. Such a use as such, as well as co-crystals or other conjugates (such as quercetin or pterostilbenoids), theacrine salts including citrate, salicylate, malate, tartrate, fumarate, succinate, nitrate, sulfate, phosphate and the like, or PEG-ylated preparations (Macrogol) may increase the functional effectiveness of theacrine.
    [048] In another modality, theacrine congeners, for example catechins and other flavonoids, can be used in an isolate, either independently or in combination with compositions based on theacrine.
    The dosage of theacrine can range from about 5 mg to about 850 mg. In another embodiment, the range can be from about 65 mg to about 300 mg. With respect to the weight of the human subject, in one embodiment the dosage can be expressed as about 0.75 mg/kg of body weight to about 3 mg/kg of body weight. In initial studies the human ED90 appears to be from about 1 mg/kg to about 3 mg/kg.
    [050] In one aspect of the invention, theacrine can be administered with caffeine. When administered with caffeine, the ratio of caffeine to theacrine, weight to weight, can range from about 0.5:1 to about 50:1, and in another embodiment, from about 1:1 to about 10: 1, and in another mode, from about 2:1 to about 4:1. Upon administration, theacrine can be administered in an amount of about 5 mg to about 800 mg with amounts of caffeine ranging from about 25 mg to about 650 mg. In another embodiment, the theacrine can be administered in an amount of about 5 mg to about 650 mg with the caffeine, and in other embodiments it can be any amount in that range. This administration provides an increase, as measured by the 100mm VAS scales, in at least one in focus, concentration, and energy, while also providing a decrease in at least one in anxiety, irritability, and feelings of overstimulation. Recommended dosages expressed in terms of amount per body weight can range from about 0.75 mg/kg to about 3 mg/kg of theacrine when administered in combination with caffeine, although theacrine can be administered in the ranges described above to about 850 mg, regardless of whether or not it is administered in combination with caffeine.
    [051] The invention can be used to treat a variety of conditions, such as improving mood, energy, focus or concentration. The invention may also promote reduced appetite, reduce perceived exertion from exercise, decrease discomfort associated with intense exercise, and may also improve sexual desire. EXAMPLESEXAMPLE 1
    [052] In order to examine the beneficial experimental effects and psychometric properties of theacrine supplementation in healthy subjects, explore the optimal dosage and potential cumulative effects in a healthy human cohort with a 7-day sub-acute repetitive administration protocol, and acquire Preliminary data on several biomarkers of safety and tolerability, an experiment was performed.
    [053] 15 healthy individuals (mean ± SD of age, height, weight, BMI: 28.3 ± 6.1 years, 175.7 ± 11.5 cm, 89.8 ± 21.7 kg, 29.1 ± 4.7) ingested 200 mg of TeaCrine™ (Compound Solutions, Inc., Carlsbad, CA) (TC) or Placebo (PLA). Anchored VAS questionnaires were used to detect changes in various aspects of energy and physical and mental performance; Side effect profiles, hemodynamics, and biochemical safety markers were also collected over a 3-h post-administration period. A subset of 6 subjects underwent a separate 7-day open-label repeat-dose study comparing 100 mg, 200 mg, and 400 mg of TC.
    [054] The experiment was a randomized, double-blind, placebo-controlled, crossover clinical trial between subjects (for study N=15). Another subset study was a repetitive administration, sub-acute (7-day), open-label trial (for subset N=6).
    [055] Six (6) subjects provided written and dated informed consent to participate in the 7-day repetitive administration study between December 15, 2012 and February 21, 2013. A separate cohort of fifteen (15) subjects provided written informed consent and dated for the acute-dose, placebo-controlled, crossover clinical trial. All subjects were in good health as determined by physical examination and medical history, between the ages of 18 and 45 (inclusive). The individual's caffeine intake from food/beverage was limited to <300 mg per day. Subjects were willing and able to comply with the experimental and supplement protocol.
    [056] Excluded individuals included individuals who were pregnant or lactating, individuals with a history of hepatorenal, musculoskeletal, autoimmune or neurological disease, diabetes, thyroid disease, adrenal disease, hypogonadism, inborn error of metabolism, personal history of heart disease, high blood pressure (systolic > 140 mm Hg & diastolic > 90 mm Hg), psychiatric disorders, cancer, benign prostatic hypertrophy, caffeine sensitivity, gastric ulcer, reflux disease, or any other medical condition considered exclusive by medical personnel, individuals who were currently taking thyroid, hyperlipidemic, hypoglycemic, antihypertensive, anticoagulant or OTC products containing pseudoephedrine or other stimulants, individuals who used any weight loss supplements within 30 days of the study, individuals who have gained or lost more than 4.54 kg (10 lbs) in the last 30 days, individuals who drank more than 1 cup of percolated coffee or 2 cups of tea per day, individuals who smoked or who had quit smoking in the past six months, individuals who had a known allergy to any of the ingredients in the supplement or placebo, and individuals who did not demonstrate a verbal understanding of the Informed Consent document.
    [057] The study did not incorporate a dietary intervention (other than supplement/placebo intake). Subjects were instructed to complete a 24-h diet record prior to their first laboratory visit, and to duplicate that 24-h diet prior to each subsequent laboratory visit. The study also did not incorporate any physical activity intervention. Subjects abstained from physical exercise and/or heavy physical activity the day before each laboratory visit.
    [058] Levels of physical activity and health history were determined using standardized questionnaires. Heart rate and blood pressure were measured using an Omron HEM-780. Standing height was determined using a wall mounted stadiometer. Body weight was measured using a 767™ Dry Medical Scale. A 100 mm anchored VAS questionnaire for energy, fatigue, and concentration was distributed to each acute laboratory session; Additional VAS questionnaires were distributed for daily assessment over a 6-hour period during the 7-day subset study. Quest Diagnostics (Pittsburgh, PA) was used for transport and analysis of all blood samples. For each laboratory session, subjects reported to the laboratory well hydrated, 10-12 hours postprandial, and at least 24 hours after their last exercise session. STATISTICAL ANALYSIS:
    [059] Descriptive statistics (mean, median, SD, 95% CIs) were used to quantify the physical characteristics of individuals. RM ANOVA, as well as analyzes of covariance (ANCOVA), using reference scores as the covariate (respectively), were used to analyze differences between trials. Alpha was set at 0.05 (P < 0.05) for statistical significance, and < 0.10 for trends. Effect sizes were also calculated. Upon arrival for the first trial session, subjects were randomly assigned to receive the respective supplement/placebo. Each individual ingested the sponsor's recommended dosage of their respective supplement (1 capsule prior to the evaluation schedule). Supplements were prepared in capsule form and packaged in generic coded containers for double-blind administration. RESULTS:
    [060] The 200 mg dose of TC caused significant improvements in energy (TC: +8.6% vs. PLA: -5.7%, P=0.049) and reductions in fatigue (TC: -6.7% vs. .PLA: +5.8%, P=0.04). A trend towards improved concentration was also observed (TC: +2.4% vs. PLA: -1.3%, P=0.07). No changes in systemic hemodynamics or side effect profiles were observed. The N=6 cohort study demonstrated moderate to large effect sizes (0.50 to 0.71) with the 200 mg TC dose over a 7-day evaluation period for the following subjective measurements: energy, fatigue , concentration, anxiety, exercise motivation and libido.
    [061] The results of the experiment are also shown graphically in Figures 2 to 7.
    [062] As shown in Figure 2, subjects who were administered theacrine reported higher energy levels at each measured time increment. Figure 3 shows that while subjects given placebo reported greater fatigue 60 minutes after administration, those given teacrine reported lower levels of fatigue. Figures 4 and 5 show that there was no substantial change in systemic hemodynamics.
    [063] Figures 6 and 7 show the results of the study with the N=6 cohort. With a 200 mg dose of theacrine over a 7-day evaluation period, theacrine was found to have a positive effect on each of energy, fatigue, concentration, anxiety, exercise motivation, and libido. That is, fatigue and anxiety were substantially decreased, while energy, concentration, exercise motivation and libido were substantially increased.
    [064] Thus, experimental data show that theacrine supplementation appears to favorably affect the various subjective and psychometric indices of energy and fatigue. These findings, as well as the potential cumulative effects on focus, concentration, and libido, are worthy of further study.
    [065] Although previously published animal data suggested that higher doses of "TC" would be needed to exert its neurophysiological effects, these early human data suggest much lower doses of 1.5 mg to 2.5 mg/kg body weight body weight (eg approximately 200 mg in a 100 kg individual) provides optimal benefit. Follow-up studies should confirm these results, explore other subjective measures of physical and cognitive function, and clarify the mechanisms by which theacrine exerts the observed salutary effects. ADMINISTRATION ROUTE
    [066] The compounds can be administered by any route, including but not limited to oral, sublingual, buccal, ocular, pulmonary, rectal and parenteral administration, or as an oral or nasal spray formulation (eg inhalation of nebulized vapors , droplets or solid particles). Parenteral administration includes, for example, intravenous, intramuscular, intraarterial, intraperitoneal, intranasal, intravaginal, intravesical (e.g., bladder), intradermal, transdermal, topical or subcutaneous administration. Also considered within the scope of the invention is the instillation of theacrine into the patient's body in a controlled formulation, with systemic or local release of the drug occurring at a later time. For example, the drug can be located in a depot for controlled release into the circulation.
    [067] The pharmaceutical compositions of the present invention can be administered in combination with a pharmaceutically acceptable carrier. The active ingredients in such formulations may comprise from 1% by weight to 99% by weight, or alternatively, 0.1% by weight to 99.9% by weight. “Pharmaceutically acceptable carrier” means any vehicle, diluent or excipient which is compatible with the other ingredients of the formulation and not harmful to the user. Useful excipients include microcrystalline cellulose, magnesium stearate, calcium stearate, any acceptable sugar (e.g., mannitol, xylitol), and for cosmetic use an oil base is preferred.
    [068] The nutraceutical compositions of the present invention can be administered in combination with a nutraceutically acceptable carrier. The active ingredients in such formulations may comprise from 1% by weight to 99% by weight, or alternatively, 0.1% by weight to 99.9% by weight. “Nutraceutically acceptable carrier” means any vehicle, diluent or excipient which is compatible with the other ingredients of the formulation and not harmful to the user. Useful excipients include microcrystalline cellulose, magnesium stearate, calcium stearate, any acceptable sugar (e.g., mannitol, xylitol), and for cosmetic use an oil base is preferred.
    [069] While the present invention has been described in relation to certain embodiments thereof, and many details have been presented in this illustration, it is to be understood that other modifications and additional modifications, in addition to those presented or suggested herein, may be made within the spirit and scope of this invention. Descriptions of embodiments shown in the drawings are not to be construed as limiting or defining the current and simple meanings of the terms of the claims unless explicitly stated.
    [070] Thus, those skilled in the art will appreciate that the design, on which this disclosure is based, can easily be used as a basis for designing other structures, methods and systems to accomplish the various purposes of the present invention . It is important, therefore, that the claims are considered to include these equivalent constructions to the extent that they do not depart from the spirit and scope of the present invention.
    [071] All references cited herein are incorporated by reference in their entirety. The present invention may be incorporated in other specific forms without departing from the spirit or essential attributes thereof and, therefore, reference should be made to the appended claims, rather than the preceding descriptive report, as indicating the scope of the invention.
    权利要求:
    Claims (12)
    [0001]
    1. DIETARY SUPPLEMENT, characterized in that it comprises from 65 mg to 850 mg of theacrine, natural or synthetic, wherein the dietary supplement further comprises caffeine.
    [0002]
    2. SUPPLEMENT according to claim 1, characterized in that it further comprises a pharmaceutically acceptable vehicle.
    [0003]
    3. SUPPLEMENT according to claim 1, characterized in that it is in a solid oral dosage form.
    [0004]
    4. SUPPLEMENT according to claim 1, characterized in that it is in a topical form for administration.
    [0005]
    5. USE OF A COMPOSITION, characterized in that it is intended for the manufacture of a drug to improve physical performance or energy in a human, in which the composition comprises from 65 mg to 850 mg of teacrine, natural or synthetic and caffeine, in which the composition provides a dosage of theacrine and caffeine in an amount of at least 0.75 mg/kg to 3 mg/kg, after administration of the composition, the human feels at least one improvement in mood, energy, focus, concentration or sexual desire or a reduction of at least one of anxiety or fatigue.
    [0006]
    Use according to claim 5, characterized in that the amount of theacrine provided is from 65 mg to 300 mg.
    [0007]
    Use according to claim 5, characterized in that the human feels a decrease in fatigue of at least 6 percent.
    [0008]
    8. USE, according to claim 5, characterized in that the human feels an increase in energy of at least 8 percent.
    [0009]
    Use according to claim 5, characterized in that caffeine is present in the composition in the amount of 25 mg to 650 mg.
    [0010]
    Use according to claim 5, characterized in that the weight to weight ratio of theacrine to caffeine is from 0.5:1 to 50:1.
    [0011]
    Use according to claim 5, characterized in that the weight to weight ratio of theacrine to caffeine is from 1:1 to 10:1.
    [0012]
    Use according to claim 5, characterized in that the weight to weight ratio of theacrine to caffeine is 1:1.2.
    类似技术:
    公开号 | 公开日 | 专利标题
    BR112016010422B1|2021-08-31|DIETARY SUPPLEMENT AND TREATMENT METHOD TO IMPROVE PERFORMANCE OR PHYSICAL ENERGY IN AN INDIVIDUAL
    TWI494103B|2015-08-01|Composition for improving sexual wellness
    KR100680121B1|2007-02-07|Formulation containing lyso-phosphatidylserine for the prevention and treatment of stress states in warm-blooded animals
    US10398701B2|2019-09-03|Theacrine-based supplement and method of use thereof in a synergistic combination with caffeine
    US20040077556A1|2004-04-22|Compositions and methods for promoting weight loss, thermogenesis, appetite suppression, lean muscle mass, increasing metabolism and boosting energy levels, and use as a dietary supplement in mammals
    US20140017341A1|2014-01-16|Composition and method for treating fat tissues and inflammatory processes
    EP1763359B1|2014-10-08|Use of pregnane glycosides in the treatment/management of obesity
    US20160213673A1|2016-07-28|Endurance formulation and use
    ES2681996B2|2020-06-02|COMPOSITIONS TO REDUCE APPETITE AND ANSIA, STRENGTHEN SATIETY, IMPROVE MOOD AND REDUCE STRESS.
    Carlo Tenore et al.2015|Coffee and depression: a short review of literature
    WO2019185439A1|2019-10-03|Natural base composition for use in the treatment of chronical stress characterized by mood and/or anxiety disorders
    US20120270860A1|2012-10-25|Methods for treating or preventing alcohol-related disorders or craving-related disorders
    EP2859896B1|2018-01-31|Pharmaceutical compositions for the treatment of muscular disorders
    US20150157672A1|2015-06-11|Kits and methods for sustained weight loss
    US20210330723A1|2021-10-28|Supplement for mitigating woman&#39;s disorders caused by ageing
    US20210137928A1|2021-05-13|Enhanced caffeinated beverage composition
    EP3651770A1|2020-05-20|Theacrine-based supplement and method of use thereof in a synergistic combination with caffeine
    WO2021137926A1|2021-07-08|Enhanced caffeinated beverage composition
    WO2018112475A1|2018-06-21|Energy compositions and methods
    WO2021151094A1|2021-07-29|Paraxanthine-based bioactive composition and method of use thereof
    KR20170005873A|2017-01-16|Oral composition for improving systemic symptoms including sensitivity to cold
    KR100814634B1|2008-03-18|Extract of juglans regia l. and nelumbo nucifera gaertn, and composition for stress-free condition comprising the same
    US20090214682A1|2009-08-27|Composition and methods for weight loss in a subject
    Armendariz et al.0|Report of the Scientific Committee of the Spanish Agency for Food Safety and Nutrition | on the risks related to the consumption of energy drinks
    同族专利:
    公开号 | 公开日
    US20150132280A1|2015-05-14|
    MX2016006103A|2017-07-27|
    US10272091B2|2019-04-30|
    EP3068240A4|2017-06-14|
    AU2021266209A1|2021-12-02|
    CN105992521A|2016-10-05|
    WO2015073576A1|2015-05-21|
    AU2014348672A1|2016-06-02|
    EP3068240A1|2016-09-21|
    CA2929666A1|2015-05-21|
    AU2020200966A1|2020-02-27|
    BR112016010422A8|2020-04-14|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE3608852A1|1986-03-17|1987-09-24|Henkel Kgaa|SEBOSUPPRESSIVE PREPARATIONS|
    RU2392836C2|2004-12-08|2010-06-27|Унилевер Н.В.|Consumer product for improvement of mental activity|
    CN1317281C|2004-12-10|2007-05-23|暨南大学|Production technology of natural 1,3,7,9-tetra methyl uric acid|
    JP4807563B2|2005-12-06|2011-11-02|株式会社伊藤園|Container-packed beverage and method for producing the same|
    ES2716226T3|2007-11-16|2019-06-11|Int Ip Holdings Llc|Edible energy composition with a low caffeine content|
    CN101289448B|2008-06-18|2010-06-09|中山大学|Method for preparing 1,3,7,9-tetramethyl uric acid|
    CN101543498B|2009-05-05|2011-05-04|中山大学|Application of bitter theophylline in preparing anti-inflammation and analgesic drugs|
    US9468645B2|2014-02-25|2016-10-18|Jho Intellectual Property Holdings, Llc|Highly soluble purine bioactive compounds and compositions thereof|WO2018211425A1|2017-05-19|2018-11-22|Ortho-Nutra, Llc|Theacrine-based supplement and method of use thereof in a synergistic combination with caffeine|
    EP3174891B1|2014-07-24|2020-01-29|W.R. Grace & CO. - CONN.|Crystalline form of nicotinamide riboside|
    WO2016144660A1|2015-03-09|2016-09-15|W.R. Grace & Co.-Conn.|Crystalline form of nicotinamide riboside|
    BR112018002168A2|2015-08-05|2018-09-18|Metro Int Biotech Llc|nicotinamide mononucleotide derivatives and their uses|
    JP6165380B1|2015-08-18|2017-07-19|レジリオ株式会社|Neural network reconstruction / activator|
    GB2542881B|2015-10-02|2020-01-01|Carr Andrew|Crystal forms of ß-nicotinamide mononucleotide|
    US10674746B2|2015-10-27|2020-06-09|Cytozyme Animal Nutrition, Inc.|Animal nutrition compositions and related methods|
    US10980764B1|2016-02-01|2021-04-20|University Of South Florida|Exogenous ketone supplements for reducing anxiety-related behavior|
    US10736861B2|2016-03-11|2020-08-11|Axcess Global Sciences, Llc|Mixed salt compositions for producing elevated and sustained ketosis|
    US11241403B2|2016-03-11|2022-02-08|Axcess Global Sciences, Llc|Beta-hydroxybutyrate mixed salt compositions and methods of use|
    US10973786B2|2016-03-11|2021-04-13|Axcess Global Sciences, Llc|R-beta-hydroxybutyrate, S-beta-hydroxybutyrate, and RS-beta-hydroxybutyrate mixed salt compositions|
    WO2018020491A1|2016-07-28|2018-02-01|Trinutra Ltd.|SYNERGISTIC COMBINATIONS OF CAFFEINE, GINKGO BILOBA AND β--PHENYLETHYLAMINE|
    IT201600124013A1|2016-12-06|2018-06-06|Solarpharm Srl|Astaxanthin based food product|
    WO2018112475A1|2016-12-16|2018-06-21|Hempep, Inc.|Energy compositions and methods|
    US11103470B2|2017-11-22|2021-08-31|Axcess Global Sciences, Llc|Non-racemic beta-hydroxybutyrate compounds and compositions enriched with the R-enantiomer and methods of use|
    US11202769B2|2017-11-22|2021-12-21|Axcess Global Sciences, Llc|Ketone body esters of s-beta-hydroxybutyrate and/or s-1,3-butanediol for modifying metabolic function|
    US11185518B2|2017-12-19|2021-11-30|Axcess Global Sciences, Llc|S-beta-hydroxybutyrate compounds and compositions enriched with S-enantiomer|
    US11180521B2|2018-01-30|2021-11-23|Metro International Biotech, Llc|Nicotinamide riboside analogs, pharmaceutical compositions, and uses thereof|
    US10820617B1|2018-03-29|2020-11-03|Government Of The United States, As Represented By The Secretary Of The Air Force|All inclusive electrolytes, vitamins, and protein powder training supplement|
    US20190313682A1|2018-04-12|2019-10-17|Metabolic Recovery Systems, LLC|Compositions and methods for supplementing the diet|
    US20210212936A1|2018-06-01|2021-07-15|Baxter International Inc.|Parenteral nutrition formulation|
    CN109043269A|2018-07-10|2018-12-21|鲁东大学|A kind of solid beverage containing bitter theophylline|
    US11129802B2|2018-08-27|2021-09-28|Axcess Global Sciences, Llc|Compositions and methods for delivering cannabidiol and ketone bodies|
    US10980772B2|2018-08-27|2021-04-20|Axcess Global Sciences, Llc|Compositions and methods for delivering tetrahydrocannabinol and ketone bodies|
    CN109350622A|2018-10-17|2019-02-19|深圳市龙格生技术有限公司|The group technology of niacinamide core carbohydrates and their derivative and pyrroloquinoline quinone and its sodium salt|
    US10973792B2|2019-02-13|2021-04-13|Axcess Global Sciences, Llc|Racemic beta-hydroxybutyrate mixed salt-acid compositions and methods of use|
    US10618927B1|2019-03-22|2020-04-14|Metro International Biotech, Llc|Compositions and methods for modulation of nicotinamide adenine dinucleotide|
    US11033553B2|2019-06-21|2021-06-15|Axcess Global Sciences, Llc|Non-vasoconstricting energy-promoting compositions containing ketone bodies|
    WO2021137926A1|2019-12-30|2021-07-08|Ortho-Nutra, Llc|Enhanced caffeinated beverage composition|
    US11241401B2|2020-02-06|2022-02-08|Axcess Global Sciences, Llc|Enantiomerically pure r-beta-hydroxybutyrate mixed salt-acid compositions|
    法律状态:
    2019-10-15| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2021-07-06| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-07-06| B15K| Others concerning applications: alteration of classification|Free format text: A CLASSIFICACAO ANTERIOR ERA: A23L 1/30 Ipc: A61K 31/353 (2006.01), A61K 31/122 (2006.01), A61K |
    2021-08-31| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 12/11/2014, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    US201361903362P| true| 2013-11-12|2013-11-12|
    US61/903,362|2013-11-12|
    PCT/US2014/065289|WO2015073576A1|2013-11-12|2014-11-12|Theacrine-based supplement and method of use thereof|
    [返回顶部]