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(12) United States Patent (10) Patent No.: US 9.468,645 B2 Owoc (45) Date of Patent: Oct

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(12) United States Patent (10) Patent No.: US 9.468,645 B2 Owoc (45) Date of Patent: Oct USOO9468645B2 (12) United States Patent (10) Patent No.: US 9.468,645 B2 OWOc (45) Date of Patent: Oct. 18, 2016 (54) HIGHLY SOLUBLE PURINE BOACTIVE (2013.01); A61K 9/0019 (2013.01); A61 K COMPOUNDS AND COMPOSITIONS 9/0095 (2013.01); A61K 9/4858 (2013.01); THEREOF A61 K3I/00 (2013.01); A61K 45/06 (2013.01); A23 V 2002/00 (2013.01) (71) Applicant: JHO Intellectual Property Holdings, (58) Field of Classification Search LLC, Davie, FL (US) CPC ..................... A23V 2002/00; A23V 2200/31; (72) Inventor: Jack Owoc, Weston, FL (US) A23V 2250/062: A23V 2250/21: A23V 2250/5108: A23V 2250/5118: A23V (*) Notice: Subject to any disclaimer, the term of this 2250/54246; A23V 2250/54252: A23V patent is extended or adjusted under 35 2250/704; A23V 2250/712: A61K 31/522; U.S.C. 154(b) by 3 days. A61K 2300/00; A61K 45/06; A61 K9/00 See application file for complete search history. (21) Appl. No.: 14/628,626 (56) References Cited (22) Filed: Feb. 23, 2015 U.S. PATENT DOCUMENTS (65) Prior Publication Data 837,282 A * 12/1906 Owoc ....................... EO1B 9/60 US 2015/O238494 A1 Aug. 27, 2015 238,292 5,973,005 A * 10/1999 D'Amelio, Sr. ... CO7C 277/08 514,565 Related U.S. Application Data 2006/0236421 A1* 10, 2006 Pennell ................ C12N 9/1007 800,278 (60) Provisional application No. 61/944,528, filed on Feb. 2009,0257997 A1* 10, 2009 Owoc .................. A61K9/0014 25, 2014. 424/94.1 (51) Int. C. * cited by examiner A6 IK3I/522 (2006.01) A6 IK 45/06 (2006.01) Primary Examiner – Debbie K Ware A2.3L 2/52 (2006.01) (74) Attorney, Agent, or Firm — David W. Barman A2.3L 2/02 (2006.01) A2.3L I/30 (2006.01) (57) ABSTRACT A6 IK 9/00 (2006.01) The invention provides nutritional Supplements, in powder, A6 IK 9/48 (2006.01) tablet or capsule dosage forms and aqueous formulations, A6 IK3I/00 (2006.01) containing one or more of the purine bioactive compounds (52) U.S. C. described including theacrine and theacrine species. CPC ................ A61 K3I/522 (2013.01); A23L I/30 (2013.01); A23L 2/02 (2013.01); A23L 2/52 20 Claims, No Drawings US 9,468,645 B2 1. 2 HGHLY SOLUBLE PURINE BOACTIVE Theacrine enhances activity levels in a dose-dependent COMPOUNDS AND COMPOSITIONS a. THEREOF Theacrine reduces inflammation. INDEX TO RELATED APPLICATIONS Theacrine reduces pain. Theacrine increases endurance. This application is a non-provisional of, and claims ben Theacrine decreases depression. efit to U.S. Provisional Patent Application Ser. No. 61/944, Theacrine alleviates sleep deprivation. 528 filed Feb. 25, 2014 the disclosure of which is incorpo During sleep deprivation with moderate-intensity exer rated herein by reference in its entirety. 10 cise, theacrine Supplementation may improve perfor TECHNICAL FIELD mance of complex central executive tasks. Theacrine in combination with other psychoStimulants This disclosure of the present invention relates generally has a synergistic effect that enhances the benefits to new chemical entities (NCEs), which are a purine alkaloid described above. compound structurally related to caffeine and abundantly 15 Theacrine may impart a beneficial hypoglycemic effect in present in Camelia kuchu, Camelia sinensis and several the management of hyperglycemia. Coffea species. The disclosure relates more specifically to 1.3.7.9-tetramethyluric acid (theacrine), (O(2), 2-Methoxy The synthesis of theacrine is achieved as follows: 1,9-dimethyl-7H-purine-6,8-dione (liberine) and (O(2), 1.7, Theacrine is synthesized from uric acid by one step. At the 9-trimethyluric acid (methylliberine) wherein a basic uric presence of potassium carbonate, uric acid is methylated by acid structure has been partially or fully methylated in 2, 3 trimethyl phosphate to give theacrine. or 4 positions. This disclosure relates specifically to The one step pathway is depicted below: theacrine, and theacrine species Such as liberine, and meth ylliberine and compositions thereof. The disclosure of the present invention includes synthetic O procedures of 1.3.7.9-tetramethyluric acid, O(2), 1.9-trim 25 ethyluric acid and O(2), 1.7.9-trimethyluric acid and their Subsequent purification to yield compounds which are HN ) O K2CO3, trimethylphosphate 99.9% pure and melting points of 228.9° C., 220° C. and 1. N --Reflux 215° C. respectively. O N 30 H H The disclosure of the present invention further relates to O compositions of matter wherein one or more of the purine alkaloid compounds is administered to mammals in combi nation with other psychoStimulants including, but not lim ited to caffeine, theobromine, theophylline, yohimbine, combinations thereof, and other compounds known in the art 35 to impart a psychoStimulant effect. In addition this disclosure of the present invention relates to nutritional Supplements, in powder, tablet or capsule dosage forms, aqueous formulations, containing one or more Stable aqueous compositions of matter useful for oral of the purine bioactive compounds described. 40 administration of at least one biologically-active form of a In addition this disclosure of the present invention relates purine alkaloid compound structurally related to caffeine to to nutritional Supplements, in powder, tablet or capsule a mammalian Subject, which compositions comprise: dosage forms, as solutions or Suspensions, aqueous formu a) 1,3,7,9-tetramethyluric acid (theacrine), (O(2), 1.9- lations, which may be used as stimulant of the central trimethyluric acid (ibertine) and (O(2), 1.7.9-trimethy nervous system and metabolic stimulant. It may also be used 45 luric acid (methylliberine) wherein a basic uric acid medically to increase locomotor activity, increase, maintain structure has been partially or fully methylated in 2, 3 and extend locomotor activity, enhance activity levels in a or 4 positions dose-dependent manner, reduce inflammation, reduce pain, increase endurance, reduce depression, impart a beneficial b) Water; hypoglycemic effect and alleviate sleep deprivation. 50 c) Water (pH range of 2.0-8.5); and d) Acqueous buffer solutions (pH range: 1.5-9.0). BACKGROUND In one embodiment, the present invention provides stable aqueous compositions of matter useful for oral administra Many stimulant nutritional Supplements are available at tion of at least one biologically-active form of a purine various retail outlets, in many dosage forms, including 55 alkaloid compound structurally related to caffeine to a tablets, capsules, powders, and liquids intended for human mammalian Subject, which compositions comprise: consumption. Most of them feature caffeine as the main a) 1,3,7,9-tetramethyluric acid (theacrine), (O(2), stimulant. Theacrine offers the advantages of caffeine with 2-Methoxy-1,9-dimethyl-7H-purine-6,8-dione (liber the addition of the other benefits included in the summary ine) and (O(2), 1.7.9-trimethyluric acid (methylliber below: 60 ine) wherein a basic uric acid structure has been SUMMARY OF THE INVENTION partially or fully methylated in 2, 3 or 4 positions b) Aqueous buffered solutions (pH range: 1.5-9.0). Some of the benefits of the present invention include: In one embodiment, the composition provides said Theacrine increases locomotor activity. 65 theacrine, or the theacrine species (as used, theacrine species Theacrine) increases locomotor activity and maintains it includes liberine and methylliberine) are present in said for extended time. aqueous composition in any amount between about 0.01% US 9,468,645 B2 3 4 and about 10% by weight based on the total weight of said prising the steps of preparing a composition according to composition, including all percentages and ranges of per the present invention; and orally administering the compo centages therebetween. sition to said mammalian Subject. In one embodiment, the composition of the present inven tion is further comprising one or more nutritional adjuvant The present invention also contemplates a method for materials selected from the group consisting of flavoring increasing endurance in a mammalian Subject, said method agents, colorants, viscosity modifiers, preservatives, fra comprising the steps of preparing a composition according grances, amino acids and their salts, vitamins, minerals, to the present invention; and orally administering the com essential fatty acids, enzymes, co-enzymes, mono-glycer position to said mammalian Subject. ides, di-glycerides, tri-glyceride ester oils emulsifiers, 10 The present invention also contemplates a method for hydrolyzed proteins, whey protein, stabilizers, flow modi reducing depression in a mammalian Subject, said method fiers, viscosity improvers, chelating agents, anti-oxidants, comprising the steps of preparing a composition according anti-microbials, benzoates, alcohols, esters of para-hydroxy to the present invention; and orally administering the com benzoic acid, propionates, preservatives, Surfactants (includ position to said mammalian Subject. ing anionic, cationic or nonionic Surfactants) or combina 15 tions thereof. The present invention also contemplates a method for In one embodiment, the composition of the present inven alleviating the deleterious effects of hypergycemia in a tion the total amount of said one or more nutritional adjuvant mammalian Subject, said method comprising the steps of materials present is present in any amount between about preparing a composition according to the present invention; 0.01% and about 10% by weight based on the total weight and orally administering the composition to said mammalian of said composition. Subject. In one embodiment, the composition of the present inven The present invention also contemplates a method for tion is further comprising one or more natural beverages, alleviating the deleterious effects of sleep deprivation in a including without limitation, milk products, soy products, mammalian Subject, said method comprising the steps of ice cream, yoghurt, citrus fruit juices, non-citrus fruit juices, 25 preparing a composition according to the present invention; and vegetable juices, or components of any of the foregoing. and orally administering the composition to said mammalian In one embodiment, the composition of the present inven Subject.
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