|HAO WANAT HA MARIAUS009827320B2 DE EL ANIMATION WITH (12 ) United States Patent (10 ) Patent No. : US 9 ,827 , 320 B2 Lin et al. ( 45 ) Date of Patent: * Nov . 28 , 2017 ( 54 ) COMPOSITIONS WITH REDUCED BITTER (58 ) Field of Classification Search TASTE PERCEPTION None See application file for complete search history . @(71 ) Applicant : The Procter & Gamble Company , Cincinnati , OH (US ) ( 56 ) References Cited @( 72 ) Inventors : Yakang Lin , Liberty Township , OH U . S . PATENT DOCUMENTS (US ) ; Koti Sreekrishna , Mason , OH 6 , 169 ,118 B1 * 1/ 2001 Bilali A61K 8 / 21 ( US ) 424 /401 2005 // 01531350153135 A1 ** 7 / 2005 2005 Popplewell . .. .. A61KA61K 8 // 11 @( 73 ) Assignee : The Procter & Gamble Company , 428 /402 . 2 Cincinnati , OH (US ) 2009 /0018213 A1 * 1 / 2009 Snyder .. .. .. .. A01N 31/ 02 514 /724 @( * ) Notice : Subject to any disclaimer , the term of this 2013/ 0243935 A1 9 / 2013 Barnekow et al. patent is extended or adjusted under 35 U . S . C . 154 ( b ) by 0 days. FOREIGN PATENT DOCUMENTS This patent is subject to a terminal dis EP 2438907 A2 4 / 2012 claimer . WO WO 98 /03153 AL 1 / 1998 WO WO 98 /05312 AL 2 / 1998 (21 ) Appl. No. : 14 /633 , 161 ( 22 ) Filed : Feb . 27 , 2015 OTHER PUBLICATIONS U . S . Appl . No. 14 /633 , 160 . * (65 ) Prior Publication Data U . S . Appl. No. 14 /633 , 163 . * Product Data Sheet for Mirapol A - 15 , downloaded Feb . 2 , 2017 , US 2015 /0238613 A1 Aug . 27 , 2015 from http :/ /dewolfchem . com / wp -content / uploads/ 2013 /08 /mirapol a15 .pdf . * Related U . S . Application Data International Search Report and Written Opinion for 13580 — PCT / (60 ) Provisional application No .62 / 065 ,846 , filed on Oct . US2015 /017896 dated Jun . 15 , 2015 . 20 , 2014 , provisional application No . 61/ 945 , 437 , Rhodia : “ Mirapol A - 15 Product Data Sheet ” , Sep . 1 , 2008 , http : // filed on Feb . 27 , 2014 . dewolfchem . com / wp -content / uploads / 2013 /08 /mirapol - a15 .pdf . (51 ) Int. Cl. * cited by examiner A61K 47134 ( 2017 .01 ) A61K 8 / 84 ( 2006 . 01 ) Primary Examiner — Frederick Krass A61K 8 / 88 ( 2006 .01 ) Assistant Examiner — Michael P Cohen A23L 1 / 22 ( 2006 .01 ) ( 74 ) Attorney , Agent, or Firm — Amanda Herman ; A23L 2 /56 ( 2006 . 01 ) Alexandra S . Anoff A610 11 / 00 ( 2006 .01 ) A23L 27 /00 ( 2016 . 01 ) (57 ) ABSTRACT (52 ) U . S . CI. A composition with reduced bitterness containing poly CPC . .. A61K 47 / 34 ( 2013 .01 ) ; A23L 2 / 56 quaternium - 2 , polyquaternium - 17 , and /or polyquaternium ( 2013 . 01) ; A23L 27 / 86 ( 2016 . 08 ) ; A6IK 8 / 84 18 . ( 2013 .01 ) ; A61K 8 /88 ( 2013 .01 ) ; A610 11/ 00 (2013 .01 ) ; A6IK 2800 / 5426 (2013 .01 ) 11 Claims, 14 Drawing Sheets U . S . Patent Novcom . 28, 2017 wwwSheet 1 of 14 . com US 9 ,827 ,320 B2 ** * - Fig . 1A frozeninyFig . 1B 21 SooooooFig ww . 101 atent Nov . 28 , 2017 Sheet 2 of 14 US 9 ,827 , 320 B2 %Polymer 20.33% 20.17% 20.08% $0.04% 20.02% 20.01% ZITIIIII LLLLLLLLILIIN Kultuur polymer LIITILI M IZDA ??????????????? MirapolMerquatLuviquatcontrol Fig.2A 100A-155502200FC905care TNTkecelakaan11 + TIMA ** 0.00 180.00 160.00 140.00 120.0000 .10000 .80 60.00 0040. 20.00 -20.00 Guaifenesin MM 2 control the of % U . S . Patent Nov. 28 , 2017 Sheet 3 of 14 US 9 ,827 , 320 B2 w %008000 A %000LOON %0010002 %080000S %0L0000a %E000000 Onuo TTTT 0111111111111111MIMI WE90603juenbungOSSOjenbung AAAAAAAAAAAA 1111111111117111111/ 71 SL-Vjodej 97811 MI W OOLlodeJiW ??????????????????ILL Leded for nnnn ge c epce pedodoodge -000 -00'09 00'OCLENNT 000 00'OVL 00'OCI 0000L 0008 0001 control the of % wwwwwwwwwwwwwwwwwwwwwwwwwwwwww atent Nov . 28 , 2017 Sheet 4 of 14 US 9 ,827 ,320 B2 10.17%MirapolA-15 00.17%LuvquatCarePlymer + + + + 80.17%Merquat2200 + + + + + + + UONO brinqimmiminho pannage luminum ment 2222222222222 UOANQUOI CarvacrolAPB-100uM8 100uM Fig.20 100UMAITC o pood ?????BUNUIT ??? "? Wull ????????????????????IZ ibuprofen 1mM + + + + + + + + Naproxen1mm gayutyukyky Lubrifice GuaifensinImM minginninginningunniyninyonstige wwwwwwwwwwwww mga Diphenhydramine1mM 10000.0 8000.0 6000.0 00Clo?edanol 1mM -2000.0 U . S . Patent Nov . 28, 2017 Sheet 5 of 14 US 9 ,827 ,320 B2 0.000047% sdow% Q0.000374% 20.000187% 20.000093% wwww 7777777777777777 GGMM 2 WXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX MA%01. 0 +CB s-RS5698A -CB WXXXXXXXXXXXXXXXXXXX MA%01. 0 +CB r -?????????????£ RS5722B-CB 3.Fig w XXXXXXXXXXXXXXXXXXXXXXXX hominent MA%01 .0 +CB que ALLITTIIIIIIII L-RS5698A -CB ??? MA%01 .0 +BB ?????? BL168003-B Units Fluorescence U . S . Patent Nov. 28 , 2017 Sheet 6 of 14 US 9 ,827 ,320 B2 %Polyquaternium-2 NoMA $0.033 20.011 0.0037 0.00123 20.00041 TOIMITI 2mMGG 7777777777TI YYYY riggingvinging tinggal binnenplannhanhnhang ganapan MIILLID Fig.4A 1011111111111111111111110L77777777SZTITITETTA TELIIIIIIIIIIIIII DicyclomineHydroxyzinePromethazineDoxepin TOIDIDIITI LIITTILA 25000- -00007 15000 0000 5000 Units Fluorescence atent Nov . 28 , 2017 Sheet 7 of 14 US 9 ,827 ,320 B2 %Polyquaternium-2 0.00123 $0.1 033.20 011.20 $0.037 a0.00041 aNoMA 2mMGG T IT WWWWW 1mM IIIIIIIIIII 2mMPhenytoin2mMOmeprazoleDiphenhydramine Fig.4B nonnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn TIT w MINIIIIIII FITTIILITSALA 1mMDiltiazem 15000+ 0 20000 -5000 Units Fluorescence U . S . Patent Nov . 28, 2017 Sheet 8 of 14 US 9 ,827 ,320 B2 %Polyquaternium-2 0.0037 B0.1 20.033 20.011 20.00123 20.00041 ENOMA | II | IIII |MITITII 2mMGG 10mMAPAP IIIIIIIIIIIIIIIIII Fig.4C 0.25%JambuSEWS 1mMEnalapril ????????????? 1mMCetirizine wa 14000 12000 4000 2000 10000 Units Fluorescence U . S . Patent Nov . 28, 2017 Sheet 9 of 14 US 9 ,827 ,320 B2 20.02%polyquaternium-2 $0.2mm MITTTTTTTTTTTTT www program programang ang pangangailangan mo ngayon KAPRIGO KAN veya lonamycinum 10 phon GG2MM wy + ????????* -1+ APARMM 5.2 -1+ WILLMAXXU * TRITTTTTTTTTTTT-177777TOITTTTT1TTTTTTTTTTTTTTTTTTT bbm WERKKRKA XARXEKRARXERRARXERRARRERKORREKARERKRORRERA XXXXXXXXXXXXXX -1+ mmmmmmmmmmmmmmmmmm ??????? ????sea nonannan alcoholethoxypyrazinevanillyl -paramethyl Fig.5A wwwwwwwwwwwwwwwwwwwwwwwwwwwwww wwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwww ?????????????????? WRXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX MYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYY phenoxyethanolhesperidin -2 * nananana who * * ennman WEKKKKKKKA XXXNXX VXXXXXXX WARREKRAARREKEN M acidanthranilic benzoyl w terpineonanthranilate-beta naphthyl -beta YYY hoghorn herg * TTEITTTTTE-LITE wwwmnnnnnnnnnnnnnnnnnn KARKAERARKIERARKEN wwwwwwwwwwwwwwwwww ?????. IKKEK anthranilatedimethyl TETETTELETTEanthranilate methyl 14000 12000 10000 8000 00 4000 2000 aminoacetophenone-2 FUS anthranit?teformyl methyl U . S . Patent Nov . 28 , 2017 Sheet 10 of 14 US 9 ,827 ,320 B2 2 No Polyquaternium - 2 0 .01 % polyquaternium - 2 2000020000 - -- - - 150002 W www 100004 FUS SEXX . IDEII E . II 1 . 2 . 1 . 1 . 1 . 1 . 1 TIEDE 5000 ????????? RRRRRRRRRRRRR wallmountd16 0 ????? ADdw .?d ??????????? time J009 2.5mm Famotidine 2mM Erythromycin 0.5mm Saccharine 3%Propylene glycal 5MM Pseudoephedrine HCI 2.5mm Prednisolone 0.5mM 1 ,10-Phenanthroline R Fig. 5B U . S . Patent Nov . 28 , 2017 Sheet 11 of 14 US 9 ,827 ,320 B2 20.01%polyquaternium-2 Q2mM - + + + X + + DET+ + + + + X + + A-LAAAAAAAAAAAAAAAAAAAAAAAA *Awamemuumim + XML + + WRXXXXXXXX + * - + + + + - + * ALLADAANDAADLANANLAR + * WRXXXXXXXXXXXXXXXXXX LAKKKKKKKKKKKKKKKALE KUULUU Chlorhe?idice * WXXXXXXXX wwwwwwwwwwwwwwwwwwwwwwwwwwwwwww wwwwwwwwwwwwwwwwwwwwwwwwwwwwwwww wwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwww forfinyangarapingllogagan guzgunggangan VA hy hydrochlorideProcainamide Fig.50 * Phenanthroline-10 ,1 * + + * hydrochlorideOrphenadrine * * LAADUANDAALALALALA NAVAUXXXXX SKAAKKAAKAKKUKAKAM YYYYYYYYYYYYY Methylthiourea-N YYYYYYYYYYYYYYYYY R -XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX Kopruhgungen Caprolactam-E * EKAKK * 11min11111111 XXX * Brucine Tinggi * * KAWE wwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwww AAALAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA wwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwwww * KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK nonnornanananarinnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn BenzamideAmygdalin 14000 12000 10000 8000 0009 4000 2000 FUS U . S . Patent Nov . 28 , 2017 Sheet 12 of 14 US 9 ,827 ,320 B2 Sam diluted to 0 .617 % 10 .02 % polyquaternium - 2 18000 16000 14000 12000 K 10000 8 8000 * 6000 yang 4000 * 2000 ??????????????? ??????? * * * * -2000 DayQuil® GG(2mm wan) Hyland's®PediaCare®YPE DEFEND Chestal®NyQuil® )HoneyNyQuil®Original cherry w . out wDox. out Qox DayQuil®Severe lonomycin (10 4M ) Nature'sWay® ,Umeka™ AlcoholCold -CareFree NyQuil® Mucinex®w. out CHL Fast -Max® DM Max Fig . 6 atent Nov . 28 , 2017 Sheet 13 of 14 US 9 ,827 ,320 B2 AfterExpectorationBitter InMouthBitter N3MinuteBitter 335MinuteBitter 10MinuteBitter Base+0.03%Polyquat.-2 Ex.5-HFCS6 Base+0.1%Polyquat.-2 Ex.4-HFCS LA Fig.7 Base+0.3%Polyquat.-2 coopérations podenpiteetselspoo Ex.3-HFCS Polyquat.-2 Base+1% ZITIITITZ Ex.2-HFCS IIIIIIIIIIIIIIIIIIII Widawwwdowaniu VI 1117777777777777A Ex.1HFCS anan LLLLLBase e ? ? ô c o Bitterness U . S . Patent Nov . 28, 2017 Sheet 14 of 14 US 9 ,827 ,320 B2 HIER ??????????? 10MinuteBitter 12 Ex.8ActiveFormula+01%Polyquaternium-2 3MinuteBitter5MinuteBitter Fig.8 X C DEx.7-4ActiveFormula UZAZAAR Expectoration Bitter HA InMouthBitterAfter coö o todo on Bitterness US 9 ,827 ,320 B2 COMPOSITIONS WITH REDUCED BITTER FIG . 2B compares the modulation of bitterness of solu TASTE PERCEPTION tions with different water soluble polymers in an Assay for Taste Receptors ; FIELD OF THE INVENTION FIG . 2C compares the modulation of bitterness of solu 5 tions with different