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The Two Tortoitumia Ultimate Tatli Himin THETWO TORTOITUMIAUS 20180104248A1ULTIMATE TATLI HIMIN ( 19) United States ( 12) Patent Application Publication ( 10 ) Pub . No. : US 2018 /0104248 A1 Lopez et al. (43 ) Pub . Date : Apr . 19 , 2018 ( 54 ) THEACRINE -BASED SUPPLEMENT AND Publication Classification METHOD OF USE THEREOF IN A (51 ) Int. Cl. SYNERGISTIC COMBINATION WITH A61K 31/ 522 ( 2006 . 01 ) CAFFEINE C07D 487/ 04 (2006 . 01) (52 ) U . S . CI. @( 71 ) Applicant : Ortho - Nutra, LLC , Morganville , NJ CPC .. A61K 31/ 522 ( 2013 .01 ) ; C07D 487 /04 (US ) ( 2013. 01 ) @(72 ) Inventors : Hector L Lopez , Cream Ridge , NJ (US ) ; Shawn Wells , Lewisville , TX (US ) ; Tim N . Ziegenfuss , Chardon , OH (57 ) ABSTRACT (US ) A human dietary supplement comprises theacrine and @( 73 ) Assignee : Ortho -Nutra , LLC , Morganville , NJ optionally other compounds that modulate the effects of theacrine . Uses for the theacrine - containing supplement (US ) include improvement of at least one ofmood , energy, focus, concentration or sexual desire or a reduction of at least one (21 ) Appl. No. : 15 /600 , 371 of anxiety or fatigue. A synergistic composition comprises ( 22 ) Filed : May 19 , 2017 co -administration of theacrine and caffeine , wherein the co - administered caffeine reduces theacrine oral clearance Related U . S . Application Data (CL / F ) and oral volume of distribution (Vd / F ) . In addition , the co - administered caffeine increases area under the plasma (63 ) Continuation - in -part of application No. 14 / 539, 726 , concentration time curve ( AUC ) of theacrine , and increases filed on Nov. 12 , 2014 . theacrine maximum plasma concentration ( Cmax ) in com (60 ) Provisional application No .61 / 903 ,362 , filed on Nov . parison with the corresponding pharmacokinetic parameters 12 , 2013 . when theacrine is administered alone . Covas mean ENERGY w * * * * * Wiks tamide 73474 , F18 , 25830086 , 0x04914 Come coming a means ) Vamoat tas note 0 . 86 orience interval wwwwwwwwwwwwwww . wwwwwwwwww * . ' . ' * VAS(cm) . .. * wwwwwwwwwwwwwwwinangunan the energy wwwwwwwwwwwwwwwwwwww. 3hr Energy . Waring Trial Units for verucal axis are Visual Analogue Scale ( in cm . Patent Application Publication Apr . 19 , 2018 Sheet 1 of 18 US 2018 /0104248 A1 ti antibio FIG . 1 Patent Application Publication Apr . 19, 2018 Sheet 2 of 18 US 2018/ 0104248 A1 Covariste en Wake sambdax 78674 . ( 3 . 25 08. 093 Compted to exwriales si a mans ) Vertical is die 0 .86 coniugnce alarms www vvvape . * grammar * )VAS(cm * : . wwwwwwwwwwwwww* wwwwwwwww wwwwwwwwwww*wwwwwwwwsxwewesen . * . wwwwww Hy Energy 2 egy * * ** ** * * * * * * * * * * * * * * * * * * * * * Paba Trail Units for vertical axis are Visual Analogue Scale ( in cm ). FIG . 2 Patent Application Publication Apr . 19 , 2018 Sheet 3 of 18 US 2018 /0104248 A1 FATIGUES Curontotect Fit, 28 * * . 366 , 0 . 04 wiecie hypothesis decomposition Vertical tos darote 0 . 95 oxidemo interval * * * * * * * * * * * * * * * * * * * * www . * * * VAS(cm) 2 12 . wwwwwwwwwwwwwwwwwwwwwwwwww tematamatateemat Macedo www . ** * ** ** * ** * * * ** ** W ** * * ** * * * *- - * wwwwwwwwwwwwwwwww 0 2 Units for vertical axis are Visual Analogue Scale (in en ) . FIG . 3 Patent Application Publication Apr . 19 , 2018 Shet 4 of18 US 2018 / 0104248 A1 ??????????? ??? ??? ? ?? ? Sess ?? AS ???????? - - - - - - "- " er - Pre - w eservementervers , www sincommonominme -* *- werenament - * , . … …. vvvvvvvvvvvvvv -* : * * .… … ??????????? Airitinar-reneral , ??= … …www : ? . … . .… . , … “ ? …. ,?? ?? setP?? * ". ? ,we'll - -* haowoodwww. - - *-- *-? *- *verywerewwreture . 3 = … httertest … … … … … … ????? .… … … … … weethereserversity. www ?? is is is title ?? FIG . 4 Patent Application Publication Apr. 19 , 2018 Sheet 5 of 18 US 2018 /0104248 A1 Diastolle Blood proseura Current event: F6, 3684 639 , - 0 .40 Kective hypothesi daconson Vorical bar denota 0 .96 confidence interval wwwing wwiii wwwwwwwwwwwwwwwwwwwws ? ? ??????? * .inanmaa waiiuszivis 3 *. * . * Windecisses.* . - . W @ sinirincisi w . .** * *. rici. * e w wwwwww ist iiiii W www. -4 *-: * wwwwwwwwwww wwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwsss. * placeto Teacing . .. wwwwwwwwwwwww wwwwwwwwwww 8 wwo OE LEB 04 03 06 U OM UW O NU OU EM FIG . 5 Patent Application Publication Apr . 19 , 2018 Sheet 6 of 18 US 2018 /0104248 A1 M . W . S . * . .. *. * . * , . .. * . .* . * ** * . ' ' ' * ' " ' " " " ' . * * * . *. ". - ." " ? ? ? ? ? ? ?? ? ? ? ? ? ? ? ? ? ? ?? ? ?? ? ? ?? ?? ? ? ? ? ? ? ? ? ? ? . ? . .. .. .. .. ?? ? ? ? ? . V . 1 . 3 . " 14 . - 97 . 4 . 4 . 4 . 4 . 4 . .* Ohr . * .* .* . * .* . * .* . *. .* -* 1 hr www . * * . * * * * * * * * * * * 04hr * * * * * * * * * * * * * * wwwwwww. ww * 6 hr 4VWWW Fatigue Anxiety Libido Sulewww ca m ca tots . www . * * * * * * * * * * -* * Units for vertical axis are Visual Analogue Scale (in cm ). Wlect Size 00200 mg dose 0010er course 007 - day repeated dose study relative to baseline on : Fatigue : 0 .64 , Anxiety - 0 .59 , Libido : 0 .71 FIG . 6 Patent Application Publication Apr . 19 , 2018 Sheet 7 of 18 US 2018 /0104248 A1 . .. .. .. .. .. 44 * * . * * * * * * . * WWW * * * * * * Y * * * * * * * * * * * * * * * * * * * 11. * . , ? ? ? ? ? ? ? ? ? ? . * . VASunits Ohr * * * word.com * * 1 hr * * 88888 04hr * * a$plexo .* * Adieus Motivationto 6 hr W * uopepua10 W . Units for verticalaxis are Visual Analogue Scale ( in cm ). Size of 200 mg dose of Gover course of day repeated dose study relative to baseline on : Energy : 0 .63 , Motivation to Exercise: 0 .58 Concentration 0 .60 FIG . 7 Patent Application Publication Apr . 19 , 2018 Sheet 8 of 18 US 2018 /0104248 A1 * Sitat * Subed 2 within SubedSubsect3 Theacrino(ng/mL) southern Subc4 SubjectsSutecto Subedo Subsct7 + Subedi 130 The (Hr ) FIG . 8 ( A ) Patent Application Publication Apr . 19 , 2018 Sheet 9 of 18 US 2018 /0104248 A1 10000 + Subject 1 * SubjectSubect 2 + Subject3 Theacrine(ng/mL) +- Subject 44 . * Subject 5 Subject 6 # Subject 7 * Subect 8 100 + . ? . ? . ? . ? . ? . ? . ? . ? . ? . ? . ? . ? . ? . ? . ? . ? . r . - + + + + - + + + + + + + + + + + + Time (Hr ) FIG . 8 ( B ) Patent Application Publication Apr . 19 , 2018 Sheet 10 of 18 US 2018 /0104248 A1 + DUOSubject 1 + Subject2 * Subject 3 mL)ng/Theacrine( the Subct 4 * Subjects + Subject 6 Subject 7 Subject 8 Time (HO ) FIG . 8 ( C ) Patent Application Publication Apr . 19 , 2018 Sheet 11 of 18 US 2018 /0104248 A1 ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? MATGESVAT CUF AUCH sieleweledyd sx , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 . WWWWWWW 2x www Mafite 1. 050515253 . - 25 mg theacrine and + - 125 mg theacrine in combination with 150 mg caffeine MRT0- « , mean residence time zero to infinity ; CL / F , oral clearance ; Vz / F , oral volume of distribution ; AUCow , area under the curve from zero to time infinity (dose normalized ) ; Cmax , maximum plasma concentration (dose normalized ) ; Tmax , time to reach maximum plasma concentration . FIG . 9 Patent Application Publication Apr . 19 , 2018 Sheet 12 of 18 US 2018 /0104248 A1 10000 + Subject 1 + Subject 2 + Subject 3 Caffeine(ng/mL) Subject 4 ng magulang + Subject 5 monterest Subject 6 terimakasama # Subject 7 ang + Subject 8 10 20 Time (Hr ) FIG . 10 ( A ) Patent Application Publication Apr . 19 , 2018 Sheet 13 of 18 US 2018 /0104248 A1 10000 + Subject 1 + Subject 2 pumuntansi * Subject 3 terra! Caffeine(ng/mL) L : ** Subject 4 etted * Subjects mtineret pentru Subjecto Subject7 Subject8 op 10 20 Time (Hr ) FIG . 10 ( B ) Patent Application Publication Apr . 19 , 2018 Sheet 14 of 18 US 2018 /0104248 A1 .. .. .. MRTO w CUF VE AUCO WW *. PKparameters W max . ww BX . .. .. .. Halt lite 0 . 0 ??? ??0 . ??2 ?? ???? ???0 . 4??? ??? ?????? 0 . 6??? ??? ??? ??? ??0???? . 8???? ???? ???? 10ww 12 14 16 18 20 single caffeine dose ( 150 mg) alone or in combination with theacrine (125 mg) FIG . 11 Patent Application Publication Apr . 19 , 2018 Sheet 15 of 18 US 2018 /0104248 A1 1 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + ++ + + + + + + + + * . ww: ** * . w * * Heartratobeatoperminute . w * * * wygenerowany 10 Mme post- cose (an ) Single dose theacrine 25 mg ( - - - ), theacrine 125 mg ( - - - ) , caffeine 150 mg ( - - ) , theacrine 125 mg plus caffeine 150 mg ( - A - ) . FIG . 12 ( A ) Patent Application Publication Apr . 19 , 2018 Sheet 16 of 18 US 2018 /0104248 A1 (Oy : * www * * * * * * * * * * * * * M )08116530poogworks * 3 8 ** ** * * w 12. 16 .. 20 .. 24 Tuno post- dose ( M ) Single dose theacrine 25 mg ( - - - ), theacrine 125 mg ( - - - ), caffeine 150 mg ( - - - ) , or theacrine 125 mg plus caffeine 150 mg ( - A - ) . FIG . 12 ( B ) Patent Application Publication Apr . 19 , 2018 Sheet 17 of 18 US 2018 /0104248 A1 8 WWW V . V . W - * W * . * . * * . * . * * . * * . 8 COMWor) * 8 * * w * 8 * $300oogvoed * 8 8 wwwwwwwwwwwwwwww Time posidase Single dose theacrine 25 mg ( - . - ), theacrine 125 mg (- - - ) , caffeine 150 mg ( - - - ), or theacrine 125 mg plus caffeine 150 mg ( - A - ) . FIG . 12 ( C ) Patent Application Publication Apr . 19 , 2018 Sheet 18 of 18 US 2018 /0104248 A1 16000 WWWWWWWWWWWWWWWW ( * : * sim *Firma * Rex kW)Bioordasusidand * * * * * * * * * * * ** Tina post- dose ho Single dose theacrine 25 mg ( - . - ) , theacrine 125 mg ( - - - ), caffeine 150 mg ( - . - ) , or theacrine 125 mg plus caffeine 150 mg ( - A - ). FIG . 12 ( D ) US 2018
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