PAT rt Fe100mg tem RsRET eA * 20238F SFRBUET (SBSH) 20218 4MET BAREG ROME S 872399 ROM ABET ANTS 7 (FD) SL ABS PA7r4 Fie100mg wee —F YJa-F 23990151020 BRLRBR Acofide Tablets 100mg, RRS Hts HORBLEL aRESS RES 22500AMX00868000 IesehAteE A 201388 6B Sik - A Rk SRT A ae mE unmeR TE) PE BMS OMAR £ Y (BTS cE BNE Paty ® Fie kaDee 2RB (ROBBERS LEVEE) ARI ORDO L. BED REED & 6B 3. ABR + HER 3.1 ABA PAT 74 KR100mE ax ey AFT = MERE KAD 100mgSUA, ERE LO 2, {AE ct kose7oeea-z, eka YAEL 2, PEEK 1 smal BAT PU YB 7AV9L E70 AOA, BMF RY ROALF ING 9 3.2 BOER Paz rt Kae100mg Sue FAW A-F 4 v8 aa Bf an we CO) oa |C He (9.1mm xee Bs 42mm as 257mg 4, PIER SRR MRT. ASTY TC SUVERAEMS, LMR, SH 5. MER ISDRIC MET SS 5.1 BRET «ANTE 7 SV BROR CORRIT 2 UE HEB SATO, 5.2 ERE ARIAS <5) BRU ORM QO RMR ART Sct. 6. RERUAB RARITY AFT & FiSReKAD e LC 16] 00me% 183), Be: 7. BERUARC RET SER TA AR 1 2 BRS LCF EROMB AH o NG MBA EAMORSPILCAIRT 4 CE, 12 ERO? SBA RD RBO ORES SRL. LAE ARIRETIC OA. QC TORE ORD ERTT 2 OE. 8. BECRANER BLAM LFA YEAF I—LBRA CH) FFI Y YOUBET 5 OC, RSS. I BRLT BUC o CBRERSL BS FIER 9. SEOUREAT SESS SIR 9.5 SERSERPLULEIR LCs SEARED & SACHEM ARLE ORES ORES LES CMTS BAI OME ST ack, 9.6 BALM SM LORRER USAR OBR BL BILOMAMLICRIL CHR T SCL. Fy hOB Sc eaeeencosl, 9.7 EE INAS ETRE LC AURBUB SIE LT Le be 9.8 BRS SOB W S ATABEIC IL, GRIT Be CURT 5 Ce, ARICA (ROE - HORSE) AMER LTH, 10. 8B 10.2 GEER RICER TS ce) RASS EPRI «SBA wr - RAF BMT EFA YEAFI— AY AERC T RA ar 7 ROE DREN AMOEBA EET 2 BENS VIREERERT ow. HAY Be VAOGRBIC £ 9 ARIOFER OID TEAL ROS Benz. AY VRE IU Y LAT? — eA AUB OGRE CHER OURAS | BA CHIC Te Fob Y SEES PRP ARDS HBABHED HS. RMB S 2. BARES SY RUDE 11. BA ROBMFAYS DNS TERBS OC WBRETPIAT RAB AGBI S MBAS AES ERIE T Be CHET WABI TE, 11.2 ZOOM Ibe 0.5 ~ 196A O.S% ARI | SRE7RB ¥ RB JOSE RE Me Annee HAOHER EW BHR Ris, (Bb Fe, Wot as DAs ie ALTHBON, ASTI Mpey Ley on, y-Grpisan dn OeRALPseAN MPIIF Fit EB AD Mm MP RY Fy Y Feo14. BALOER 14.1 RARAHOTE PIPED RAPTPS — bm SARY MH LCHRADT % & SFE SCE. PIP — b ORRMR PABA LBC IRSRFLE SC CRORE OHEIB AGES HIRED 2 CE 1 15. ZO WOE 15.2 FERRIC ES < 1H Fy O24 9 NDA A DREERERIC BUC, FRAMES 200meIke/E, 6OOmpke/E, 2,000mgkg ECE NS ASSO. 8/50, SISOBIICEE DA, COOmpke/A (SASRURIT CARRE MOOI) BF CRRCHIM Lt. — DB ABCD EA HATRED Dot, Rhy LIAO n AMAA MME 2,000mgikg/E (HSURIT CHERAB OMUS30{8) C.F ARID BLT FET UTE OA BURL C2,000me/ke/ A CAS O BORE IA BRI & tite dba 16. REAR 16.1 ME 16.1.1 BERS RABIES, AIRE (7 AT 7S MERMAID LC 100me) @ZERRISICRIEEIBSS Lie & Sma ARBRE UO ERAN 7 X — 2 (ALL ROBY CHAD, Y. BERBERA. FSA tHE, 1-6 ° 30 20 0 0 5 5-01 (hr) AABURS Li & & OSA 9 x — % RSE Tmax Cmax AUCint Ti (mg) (hr) (ng/mL) (ng + hv/mL) (hr) 100 2.4240.97 | 308221333 | 171.3259.43 | 13.3146.91 SMES, os AUCing: SESRIERSALD SSRIS COME LTH L TEAUC 16.1.2 RRS RRABIEI. AAR (TAFT > FSR e LC 100mg) #1838), 98 (BBS 8B), 3~(g/L) 0 Fi, 1-6 RR STAR SRE FRNA UN 10 20035000 5 fF (hr) 16.2 BR 16.2.1 ROWE RRABSIK. ARIE (TIFT 5 FRADE LC 100mg) SSRIS, RBTNLIS IOS Le LE, Cpa dR THR SS SHIRAI SO2 LAL. Fh, PHESOC,,.. (ERS 59.6% CH 2 foo AUC It. RES CR EES. SIRISR URAC UCNT 1 T7684 U'RO.0% I Laa, i> agém) 10 3 si EE RBS UN 16.3 5 16.3.1 ERASE In vitro FORA C85 hf MRE. & b MIE CRA.21%~85.95% EMT LTS 85,10%TH), RE ORARE RL Kk, ERG SRAILT LT Sy CBA SHTML, 16.4 Heit 16.4.1 RR ELA BEB (4e] 7 FSR (600mg/03 Ci) SAPS OSS Lee 3. MURR RT 120 5, 6.0 TABI ES SOTHO Ke. TOA, MOVES IIL 770 ILE, ABER 7107 0 VBEOG AR UBL 7 7A CRD LY 2 ROR ROE 16.4.2 BERhCYPRERRE 7 RY LEAL £9, ARIACYP2CE, CYPIAINIECYP3AIE £9 T Bet vy Foe © hUGTIERAS 70 FB fein vitro CABS EBS EY, ARUIEUGTIASSUSUGTIASIS £2 CARBER® 7-2 8 RED EHRI HESS LBA DHS. 16.5 Heit BRERA BION. (4c) TAF ETI. SERRE 17. BPR ALB 17.1 AMERURLE CTS RR 17.1.1 BABIN PGR, LABADITSS, NRSRERRE EMDR Yo OWNREIET 1 AN 7D 7 REED eR ICL LE BRR ARO MAIL BD EY) Ta ARIE (PAF = PiReteAe LT 100mg) SMI A3E, sBMBORS LACS, 220 PRA MRA CHS RPAOMROMEH) RU ER (RARE, LRA. SHMREE) OA WT. FPR SNE RE S 7, Ee, SERIO IER UAE CARGO META OR OMB TRO t BY CHE, JED) Romel RAE UC. RIBS + ALL baie RR. LI SUMO RK 1 OL, LBL, RENG3 » ALLA 0 BROIL CL 5 20~ 640 BT () PRERRBAB A RSGHRIEPILG) KEV SRRHOMRORSS FSR (6OOmg/103uCi) SPF BOIS Lice S. SIGIR EACBBINEE TIRED 92 THUS. 3765 HEES A (GNBAF—2) 6 TF RE 300mg/ BRE (44268) Sofi) AD py 1s4 235 BRE DEDROMR (%) BY 348 52.2 [oseteARRR) [30.5, 39.3] [47.6, 56.7] BAR ORORE (%) : 174 [ose] (11.0, 23.7] rig =D : p<0.001 FE2) URS OED (TERAB: [APACS]. (RCo). [DLE Kok), [Bhot F >A 6% (Lol4sop) . ALTIEANI.8% (8/450) . 774 RCMP TOF 7 Fv HN4.8% (21/4426). BHI23% (10/4426) TH otc. [8.2 S96] 17.1.2 BARBERS RR CRAG LIRR SNGUMER EERE TBR T 1 287 TE BUC. ABO ER BSEROBRROREMEI LY RR BHR chub AT PSC eA REE ST RSI SUT, PSG RUGBGO (PRAONROMME) (2S H48.9% (193/395Hl) MU48.9% (69/1419) CH ate. 24BAS ECD ARS SIRS & BS OSHIP THY AA ORIRS AWE ES AGRO NTU, 6. RRB £ SARIRBIIATS.1% Gos40sfl) T Zo 550.7% (1543046) PROBE RRL. AROMS ORT 3E8) Romel NBME. AIRINGS BILLA A > SER, LER, ANTMRO RRS 11 LAL. RAVES 2 RULERS J ROSH TL 320~ TROBE BPE ORERIRME (2 11.5% (4714086)) “Ca of. SE RIERBL. GER, RY 22.2% (/4086H)) | ALTAR 1.5% (6/408fil) CH > 7:5 [8.2 4808 18. RAE 18.1 (ERIE PRE LAY YEATF EP BERL (in vitro) 5 18.2 AC RTE 4 ROR S AES) OBR y |b OBA EAEMOTURIEBe MRL. EK. A RRUFY bO 7 O=Y VBR APSE ROBBER L RD, 18.3 SHERRIE PARES ALERED EAE 1 19. ARRIBA SCP. ROL PAF? > iRakAD (JAN) Acotiamide Hydrochloride Hydrate (JAN) Acotiamide (INN) et NV. {2- [Bis (I-methylethyl) amino] ethyl} -2-[(2-hydroxy-4,5-dimethoxybenzoyl) amino] thiazole-4- carboxamide monohydrochiloride trihydrate DFR CyyHygNqOsS * HCl» 3H,0 BFE 541.06 te AG ~ RB ORIG OBA TH S. NNYX Fila PS IPA RITT KAR HBR EA/ AW (99.5) ORBITS IK TAN RUT RS PU ILIRBUI CK eR I Fu bngaasyDUBE CU. ART FROSTY VISIR EA ERIE {eet on A oe Ayr wry Tec r HCI - 3t0 ne 7 Now RRS HEL, 20. BARU LOE PTPLRBOS METAS LUT TURES SC ES 22. BR PIPE 1008 (108E10) . SOOKE (LOKE<10«5) 23. ERM DATARS: SIMS £ URE COE PNEIRS (Fb) GRRBEFAA: 20134F3A25A, CTD26.4.6) DeHABA: 240 BEARER (Fy bh) CRQBREAA: 201383 A25A, CTD2.6.6.5) SARA: 240 ROA Beta (V7 2) (HGBIERA: 201343 A25A, CTD2.6.6.5) 4) ABR RFRA RIT RS (ras2V 72%) GFERFAA: 20138F3925R, CTD26.6.5) SHARE: SUGARS (EIR Sate) (AEVEAA: 2013439258, CTD2.7.6.1) OAR: BURGER (REISER) (REA: 201343R25H, CTD27.6.1) TA: SRR (ROR) (RVEAA: 201383A25H, CTp27.64) 8) FLEE: EDRGUR (MERE SRO PIER; IBD) (FGBEAA: 20134F3525A, CTD26.4.4) 9) #EPUBBRL: Mass Balance and Metabolism Study (SSHBESERSU) 10) #LPS#H#}: Metabolite Profiling of Acotiamide (Human Mass Balance Study) (ARSE AA: 2013838258. CTn2. 722) 1) Furuta S. etal: EurJ Pharmacol. 2004; 497: 223-231 12) Matsueda K. et al.: Gut. 2012; 61: 821-828 13) tt ABS: BIRGER (FOVEAA: 201383A25A, CTD2.7.6.3) 1) tA: RMR SRR (FGBEAA: 201343 825H. CTD2.7.6.3) 15) Matsunaga Y. etal: J Pharmacol Exp Ther. 2011; 336: 791-800 16) Nagahama K. et al.: Neurogastrocnterol Motil. 2012; 24: 566-574 17) Kawachi M. etal.: Eur J Pharmacol. 2011; 666: 218-225 24. SRBRARUMVADER CUT RRIRARSH SRE 103-8351 FORABP RR ABA 10-11 TEL (03) 3661-0277 FAX (03) 3663-2352 SBAHSRS 9:00~ 17:50 (-LERRE - MALARE BRS) 26. WERT RAS 26.1 SBME 7a Lat RK A ARHG AAT 10-11