TWI577392B - ［（１ｓ）－１－｛［（２ｓ，４ｒ）－４－（７－氯－４－甲氧基異喹啉－１－基氧基）－２－（｛（１ｒ，２ｓ）－１－［（環丙基磺醯基）胺甲醯基］－２－乙烯基環丙基｝胺甲醯基）吡咯啶－１－基］羰基｝－２，２－二甲基丙基］胺基甲酸１，１－二甲基乙基酯之可溶性膠囊調配物 - Google Patents
［（１ｓ）－１－｛［（２ｓ，４ｒ）－４－（７－氯－４－甲氧基異喹啉－１－基氧基）－２－（｛（１ｒ，２ｓ）－１－［（環丙基磺醯基）胺甲醯基］－２－乙烯基環丙基｝胺甲醯基）吡咯啶－１－基］羰基｝－２，２－二甲基丙基］胺基甲酸１，１－二甲基乙基酯之可溶性膠囊調配物 Download PDFInfo
- Publication number
- TWI577392B TWI577392B TW102116102A TW102116102A TWI577392B TW I577392 B TWI577392 B TW I577392B TW 102116102 A TW102116102 A TW 102116102A TW 102116102 A TW102116102 A TW 102116102A TW I577392 B TWI577392 B TW I577392B
- Authority
- TW
- Taiwan
- Prior art keywords
- formulation
- range
- compound
- auc
- active pharmaceutical
- Prior art date
Links
- -1 Cyclopropylsulfonyl Chemical group 0.000 title description 19
- 239000007963 capsule composition Substances 0.000 title description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 title description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 title 1
- 150000001412 amines Chemical class 0.000 title 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 title 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 title 1
- 239000000203 mixture Substances 0.000 claims description 154
- 238000009472 formulation Methods 0.000 claims description 134
- 150000001875 compounds Chemical class 0.000 claims description 63
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 55
- 239000002775 capsule Substances 0.000 claims description 52
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 28
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 28
- 229920000053 polysorbate 80 Polymers 0.000 claims description 28
- 239000002904 solvent Substances 0.000 claims description 26
- 239000004094 surface-active agent Substances 0.000 claims description 25
- 239000004322 Butylated hydroxytoluene Substances 0.000 claims description 24
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical group CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 24
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 24
- 229940095259 butylated hydroxytoluene Drugs 0.000 claims description 24
- 239000003381 stabilizer Substances 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 19
- 150000004667 medium chain fatty acids Chemical class 0.000 claims description 17
- 125000005456 glyceride group Polymers 0.000 claims description 14
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 14
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 12
- 239000008380 degradant Substances 0.000 claims description 9
- 230000036470 plasma concentration Effects 0.000 claims description 9
- 208000015181 infectious disease Diseases 0.000 claims description 8
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims description 6
- 229930003427 Vitamin E Natural products 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 5
- 239000011709 vitamin E Substances 0.000 claims description 5
- 229940046009 vitamin E Drugs 0.000 claims description 5
- 235000019165 vitamin E Nutrition 0.000 claims description 5
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 229960005070 ascorbic acid Drugs 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- 235000019282 butylated hydroxyanisole Nutrition 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 235000010388 propyl gallate Nutrition 0.000 claims description 3
- 239000000473 propyl gallate Substances 0.000 claims description 3
- 229940075579 propyl gallate Drugs 0.000 claims description 3
- 239000004255 Butylated hydroxyanisole Substances 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 229940043253 butylated hydroxyanisole Drugs 0.000 claims description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims description 2
- 230000014759 maintenance of location Effects 0.000 claims description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims 2
- 229920001214 Polysorbate 60 Polymers 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000243 solution Substances 0.000 description 31
- 238000000034 method Methods 0.000 description 27
- 239000003826 tablet Substances 0.000 description 19
- 229940079593 drug Drugs 0.000 description 18
- 239000007903 gelatin capsule Substances 0.000 description 18
- 229940068968 polysorbate 80 Drugs 0.000 description 18
- 238000007908 dry granulation Methods 0.000 description 16
- 241000711549 Hepacivirus C Species 0.000 description 14
- 230000009246 food effect Effects 0.000 description 13
- 235000021471 food effect Nutrition 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- 241000282472 Canis lupus familiaris Species 0.000 description 12
- 239000000499 gel Substances 0.000 description 12
- 239000007937 lozenge Substances 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 150000002632 lipids Chemical class 0.000 description 9
- 238000011068 loading method Methods 0.000 description 9
- 238000005550 wet granulation Methods 0.000 description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 description 8
- 239000003963 antioxidant agent Substances 0.000 description 6
- 230000003078 antioxidant effect Effects 0.000 description 6
- 235000006708 antioxidants Nutrition 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 239000007916 tablet composition Substances 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 108010050904 Interferons Proteins 0.000 description 5
- 102000014150 Interferons Human genes 0.000 description 5
- LDVVMCZRFWMZSG-UHFFFAOYSA-N captan Chemical compound C1C=CCC2C(=O)N(SC(Cl)(Cl)Cl)C(=O)C21 LDVVMCZRFWMZSG-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 229940079322 interferon Drugs 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 229920002785 Croscarmellose sodium Polymers 0.000 description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 4
- 229960001681 croscarmellose sodium Drugs 0.000 description 4
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 235000012054 meals Nutrition 0.000 description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 4
- 239000008108 microcrystalline cellulose Substances 0.000 description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 3
- 108010047761 Interferon-alpha Proteins 0.000 description 3
- 102000006992 Interferon-alpha Human genes 0.000 description 3
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940088679 drug related substance Drugs 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 150000003626 triacylglycerols Chemical class 0.000 description 3
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- BHIZVZJETFVJMJ-UHFFFAOYSA-N 2-hydroxypropyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(C)O BHIZVZJETFVJMJ-UHFFFAOYSA-N 0.000 description 2
- GHHURQMJLARIDK-UHFFFAOYSA-N 2-hydroxypropyl octanoate Chemical compound CCCCCCCC(=O)OCC(C)O GHHURQMJLARIDK-UHFFFAOYSA-N 0.000 description 2
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 2
- 102100021022 Gastrin Human genes 0.000 description 2
- 108010052343 Gastrins Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 108010079943 Pentagastrin Proteins 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- 101800001838 Serine protease/helicase NS3 Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- AOBORMOPSGHCAX-UHFFFAOYSA-N Tocophersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000007888 film coating Substances 0.000 description 2
- 238000009501 film coating Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229960001021 lactose monohydrate Drugs 0.000 description 2
- 150000004668 long chain fatty acids Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000002711 medium chain fatty acid esters Chemical class 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- ANRIQLNBZQLTFV-DZUOILHNSA-N pentagastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1[C]2C=CC=CC2=NC=1)NC(=O)CCNC(=O)OC(C)(C)C)CCSC)C(N)=O)C1=CC=CC=C1 ANRIQLNBZQLTFV-DZUOILHNSA-N 0.000 description 2
- 229960000444 pentagastrin Drugs 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 229940044519 poloxamer 188 Drugs 0.000 description 2
- 229920001993 poloxamer 188 Polymers 0.000 description 2
- 229940113116 polyethylene glycol 1000 Drugs 0.000 description 2
- 229940026235 propylene glycol monolaurate Drugs 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 2
- 229960000984 tocofersolan Drugs 0.000 description 2
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 239000002076 α-tocopherol Substances 0.000 description 2
- 235000004835 α-tocopherol Nutrition 0.000 description 2
- LAPJKAPBVNANHS-UHFFFAOYSA-N 1-O-decyl 2-O-(2,3-dihydroxypropyl) benzene-1,2-dicarboxylate Chemical compound C(C=1C(C(=O)OCC(O)CO)=CC=CC=1)(=O)OCCCCCCCCCC LAPJKAPBVNANHS-UHFFFAOYSA-N 0.000 description 1
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
- YFXGICNMLCGLHJ-RSKRLRQZSA-N 2,2-dimethylpropyl (2s)-2-[[[(2r,3r,4r,5r)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-naphthalen-1-yloxyphosphoryl]amino]propanoate Chemical compound C1=CC=C2C(OP(=O)(N[C@@H](C)C(=O)OCC(C)(C)C)OC[C@H]3O[C@H]([C@]([C@@H]3O)(C)O)N3C=4N=C(N)N=C(C=4N=C3)OC)=CC=CC2=C1 YFXGICNMLCGLHJ-RSKRLRQZSA-N 0.000 description 1
- WITKSCOBOCOGSC-UHFFFAOYSA-N 2-dodecanoyloxypropyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(C)OC(=O)CCCCCCCCCCC WITKSCOBOCOGSC-UHFFFAOYSA-N 0.000 description 1
- NYPIRLYMDJMKGW-VPCXQMTMSA-N 4-amino-1-[(2r,3r,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]pyrimidin-2-one Chemical compound C[C@@]1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 NYPIRLYMDJMKGW-VPCXQMTMSA-N 0.000 description 1
- LZAUGCMVNLZVJV-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-n-methyl-5-[2-methyl-5-[(1-pyrimidin-2-ylcyclopropyl)carbamoyl]phenyl]-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1)C)=CC=1C(=O)NC1(C=2N=CC=CN=2)CC1 LZAUGCMVNLZVJV-UHFFFAOYSA-N 0.000 description 1
- WPMJNLCLKAKMLA-UHFFFAOYSA-N 5-(3,3-dimethylbut-1-ynyl)-3-[(4-hydroxycyclohexyl)-[(4-methylcyclohexyl)-oxomethyl]amino]-2-thiophenecarboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C1CCC(O)CC1 WPMJNLCLKAKMLA-UHFFFAOYSA-N 0.000 description 1
- XBEQSQDCBSKCHJ-UHFFFAOYSA-N 5-[[6-[2,4-bis(trifluoromethyl)phenyl]pyridazin-3-yl]methyl]-2-(2-fluorophenyl)imidazo[4,5-c]pyridine Chemical compound FC1=CC=CC=C1C1=NC2=CN(CC=3N=NC(=CC=3)C=3C(=CC(=CC=3)C(F)(F)F)C(F)(F)F)C=CC2=N1 XBEQSQDCBSKCHJ-UHFFFAOYSA-N 0.000 description 1
- PVRFQJIRERYGTQ-DSQUMVBZSA-N 9-[(2s,4ar,6r,7r,7ar)-7-fluoro-7-methyl-2-oxo-2-propan-2-yloxy-4,4a,6,7a-tetrahydrofuro[3,2-d][1,3,2]dioxaphosphinin-6-yl]-6-ethoxypurin-2-amine Chemical compound C([C@H]1O2)O[P@@](=O)(OC(C)C)O[C@H]1[C@](F)(C)[C@@H]2N1C(N=C(N)N=C2OCC)=C2N=C1 PVRFQJIRERYGTQ-DSQUMVBZSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 102100040018 Interferon alpha-2 Human genes 0.000 description 1
- 108010079944 Interferon-alpha2b Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 241000183024 Populus tremula Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 235000009499 Vanilla fragrans Nutrition 0.000 description 1
- 235000012036 Vanilla tahitensis Nutrition 0.000 description 1
- 244000263375 Vanilla tahitensis Species 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 229960002118 asunaprevir Drugs 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- 235000021028 berry Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- NBRBXGKOEOGLOI-UHFFFAOYSA-N dasabuvir Chemical compound C1=C(C(C)(C)C)C(OC)=C(C=2C=C3C=CC(NS(C)(=O)=O)=CC3=CC=2)C=C1N1C=CC(=O)NC1=O NBRBXGKOEOGLOI-UHFFFAOYSA-N 0.000 description 1
- 229960001418 dasabuvir Drugs 0.000 description 1
- BMAIGAHXAJEULY-UKTHLTGXSA-N deleobuvir Chemical compound C12=CC=C(C(=O)NC3(CCC3)C=3N(C4=CC(\C=C\C(O)=O)=CC=C4N=3)C)C=C2N(C)C(C=2N=CC(Br)=CN=2)=C1C1CCCC1 BMAIGAHXAJEULY-UKTHLTGXSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 1
- 229960001596 famotidine Drugs 0.000 description 1
- SLVAPEZTBDBAPI-GDLZYMKVSA-N filibuvir Chemical compound CCC1=NC(CC)=CC(CC[C@]2(OC(=O)C(CC3=NN4C(C)=CC(C)=NC4=N3)=C(O)C2)C2CCCC2)=C1 SLVAPEZTBDBAPI-GDLZYMKVSA-N 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 208000010710 hepatitis C virus infection Diseases 0.000 description 1
- 229920001903 high density polyethylene Polymers 0.000 description 1
- 239000004700 high-density polyethylene Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229940057917 medium chain triglycerides Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- XMZSTQYSBYEENY-RMKNXTFCSA-N n-[4-[(e)-2-[3-tert-butyl-5-(2,4-dioxopyrimidin-1-yl)-2-methoxyphenyl]ethenyl]phenyl]methanesulfonamide Chemical compound C1=C(N2C(NC(=O)C=C2)=O)C=C(C(C)(C)C)C(OC)=C1\C=C\C1=CC=C(NS(C)(=O)=O)C=C1 XMZSTQYSBYEENY-RMKNXTFCSA-N 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 239000008184 oral solid dosage form Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 1
- 229940050929 polyethylene glycol 3350 Drugs 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- RYXIBQLRUHDYEE-UHFFFAOYSA-M potassium;5-(cyclohexen-1-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound [K+].C1CC(OC)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C([O-])=O)C(=O)C1CCC(C)CC1 RYXIBQLRUHDYEE-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- TTZHDVOVKQGIBA-IAAJYNJHSA-N propan-2-yl (2s)-2-[[[(2r,3r,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@]2(F)C)O)COP(=O)(N[C@@H](C)C(=O)OC(C)C)OC=2C=CC=CC=2)C=CC(=O)NC1=O TTZHDVOVKQGIBA-IAAJYNJHSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- FGHMGRXAHIXTBM-TWFJNEQDSA-N s-[2-[[(2r,3r,4r,5r)-5-(2-amino-6-oxo-3h-purin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-(benzylamino)phosphoryl]oxyethyl] 3-hydroxy-2,2-dimethylpropanethioate Chemical compound C([C@@H]1[C@H]([C@@](C)(O)[C@H](N2C3=C(C(NC(N)=N3)=O)N=C2)O1)O)OP(=O)(OCCSC(=O)C(C)(CO)C)NCC1=CC=CC=C1 FGHMGRXAHIXTBM-TWFJNEQDSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- DEKOYVOWOVJMPM-RLHIPHHXSA-N setrobuvir Chemical compound N1([C@H]2[C@@H]3CC[C@@H](C3)[C@H]2C(O)=C(C1=O)C=1NC2=CC=C(C=C2S(=O)(=O)N=1)NS(=O)(=O)C)CC1=CC=C(F)C=C1 DEKOYVOWOVJMPM-RLHIPHHXSA-N 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- SSERCMQZZYTNBY-UHFFFAOYSA-M sodium;3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-phenylthiophene-2-carboxylate Chemical compound [Na+].C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1C=CC=CC=1)C([O-])=O)C1CCC(O)CC1 SSERCMQZZYTNBY-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000004250 tert-Butylhydroquinone Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 235000019281 tert-butylhydroquinone Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000010977 unit operation Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261643454P | 2012-05-07 | 2012-05-07 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201350145A TW201350145A (zh) | 2013-12-16 |
| TWI577392B true TWI577392B (zh) | 2017-04-11 |
Family
ID=48428670
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW102116102A TWI577392B (zh) | 2012-05-07 | 2013-05-06 | ［（１ｓ）－１－｛［（２ｓ，４ｒ）－４－（７－氯－４－甲氧基異喹啉－１－基氧基）－２－（｛（１ｒ，２ｓ）－１－［（環丙基磺醯基）胺甲醯基］－２－乙烯基環丙基｝胺甲醯基）吡咯啶－１－基］羰基｝－２，２－二甲基丙基］胺基甲酸１，１－二甲基乙基酯之可溶性膠囊調配物 |
Country Status (33)
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104363898A (zh) * | 2012-05-07 | 2015-02-18 | 百时美施贵宝爱尔兰控股公司 | [(1s)-1-{[(2s,4r)-4-(7-氯-4-甲氧基异喹啉-1-基氧基)-2-({(1r,2s)-1-[(环丙基磺酰基)氨甲酰基]-2-乙烯基环丙基}氨甲酰基)吡咯烷-1-基]羰基}-2,2-二甲基丙基]氨基甲酸1,1-二甲基乙基酯的口服固体给药制剂 |
| MX360452B (es) | 2012-10-19 | 2018-11-01 | Bristol Myers Squibb Co | Inhibidores del virus de la hepatitis c. |
| US9643999B2 (en) | 2012-11-02 | 2017-05-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| EP2914598B1 (en) | 2012-11-02 | 2017-10-18 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| EP2914613B1 (en) | 2012-11-02 | 2017-11-22 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| US9409943B2 (en) | 2012-11-05 | 2016-08-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| JP6342922B2 (ja) | 2013-03-07 | 2018-06-13 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｃ型肝炎ウイルス阻害剤 |
| WO2019130341A1 (en) * | 2017-12-26 | 2019-07-04 | Hetero Labs Limited | Capsule compositions comprising lopinavir and ritonavir |
| EA202092131A1 (ru) | 2018-03-14 | 2020-11-27 | Кэнди Терапьютикс Лимитед | Новый фармацевтический препарат, содержащий двойные антагонисты рецептора nk-1/nk-3 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1283041A1 (en) * | 1996-11-21 | 2003-02-12 | Abbott Laboratories | Pharmaceutical compositions containing HIV-protease inhibitors |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ526169A (en) * | 2000-10-31 | 2005-12-23 | Boehringer Ingelheim Pharma | Oral dosage self-emulsifying formulations of pyranone protease inhibitors |
| US6828301B2 (en) * | 2002-02-07 | 2004-12-07 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for hepatitis C viral protease inhibitors |
| MY140680A (en) | 2002-05-20 | 2010-01-15 | Bristol Myers Squibb Co | Hepatitis c virus inhibitors |
| ES2435799T3 (es) * | 2008-10-09 | 2013-12-23 | Anadys Pharmaceuticals, Inc. | Un método de inhibición del virus de la hepatitis C mediante combinación de una 5,6-dihidro-1H-piridin-2-ona y de uno o más compuestos antivirales adicionales |
| US8252821B2 (en) * | 2009-04-14 | 2012-08-28 | Bristol-Myers Squibb Company | Bioavailable capsule compositions of amorphous alpha-(N-sulfonamido)acetamide compound |
-
2013
- 2013-04-29 US US13/872,652 patent/US20130302414A1/en not_active Abandoned
- 2013-04-30 PT PT13722217T patent/PT2846780T/pt unknown
- 2013-04-30 HR HRP20181583TT patent/HRP20181583T1/hr unknown
- 2013-04-30 RS RS20181141A patent/RS57881B1/sr unknown
- 2013-04-30 MY MYPI2014703294A patent/MY171378A/en unknown
- 2013-04-30 LT LTEP13722217.0T patent/LT2846780T/lt unknown
- 2013-04-30 ES ES13722217.0T patent/ES2688817T3/es active Active
- 2013-04-30 SM SM20180506T patent/SMT201800506T1/it unknown
- 2013-04-30 EA EA201492039A patent/EA028749B1/ru not_active IP Right Cessation
- 2013-04-30 KR KR20147033971A patent/KR20150004921A/ko not_active Ceased
- 2013-04-30 SI SI201331126T patent/SI2846780T1/sl unknown
- 2013-04-30 SG SG11201406964QA patent/SG11201406964QA/en unknown
- 2013-04-30 PE PE2014001988A patent/PE20142439A1/es not_active Application Discontinuation
- 2013-04-30 AU AU2013260005A patent/AU2013260005B2/en not_active Ceased
- 2013-04-30 CN CN201380023724.1A patent/CN104363899A/zh active Pending
- 2013-04-30 EP EP13722217.0A patent/EP2846780B1/en active Active
- 2013-04-30 NZ NZ630248A patent/NZ630248A/en not_active IP Right Cessation
- 2013-04-30 WO PCT/US2013/038770 patent/WO2013169520A1/en not_active Ceased
- 2013-04-30 PL PL13722217T patent/PL2846780T3/pl unknown
- 2013-04-30 CA CA2872765A patent/CA2872765A1/en not_active Abandoned
- 2013-04-30 BR BR112014027676A patent/BR112014027676A2/pt not_active IP Right Cessation
- 2013-04-30 JP JP2015511510A patent/JP6276756B2/ja not_active Expired - Fee Related
- 2013-04-30 MX MX2014013220A patent/MX358545B/es active IP Right Grant
- 2013-04-30 DK DK13722217.0T patent/DK2846780T3/en active
- 2013-05-06 UY UY0001034785A patent/UY34785A/es unknown
- 2013-05-06 AR ARP130101544A patent/AR090954A1/es unknown
- 2013-05-06 TW TW102116102A patent/TWI577392B/zh not_active IP Right Cessation
-
2014
- 2014-10-27 PH PH12014502405A patent/PH12014502405A1/en unknown
- 2014-11-03 IL IL235466A patent/IL235466B/en active IP Right Grant
- 2014-11-06 CL CL2014003012A patent/CL2014003012A1/es unknown
- 2014-12-02 CO CO14265249A patent/CO7141457A2/es unknown
- 2014-12-05 ZA ZA2014/08967A patent/ZA201408967B/en unknown
-
2018
- 2018-10-15 CY CY181101051T patent/CY1120756T1/el unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1283041A1 (en) * | 1996-11-21 | 2003-02-12 | Abbott Laboratories | Pharmaceutical compositions containing HIV-protease inhibitors |
Non-Patent Citations (3)
| Title |
|---|
| A multiple ascending dose study of BMS-650032 in HCV infected subjects；https://web.archive.org/20111021202911/http://clinicaltrials.gov/ct2/show/NCT00722358，2011-10-21。 * |
| C. Pasquinelli et al., Single- and multiple-ascending-dose studies of the NS53 protease inhibitor asunaprevir in subjects with or without chronic hepatitis C. Antimicrobial agents and chemotherapy, 56(4), 1838-1844, 2012 Apr 1。 * |
| Cole ET. et al., Challenges and opportunities in the encapsulation of liquid and semi-solid formulations into capsules for oral administration. Advanced drug delivery reviews, 60(6), 747-756, 2008。 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI577392B (zh) | ［（１ｓ）－１－｛［（２ｓ，４ｒ）－４－（７－氯－４－甲氧基異喹啉－１－基氧基）－２－（｛（１ｒ，２ｓ）－１－［（環丙基磺醯基）胺甲醯基］－２－乙烯基環丙基｝胺甲醯基）吡咯啶－１－基］羰基｝－２，２－二甲基丙基］胺基甲酸１，１－二甲基乙基酯之可溶性膠囊調配物 | |
| US20250177320A1 (en) | Pharmaceutical formulations of phloroglucinol and trimethylphloroglucinol | |
| US11260038B1 (en) | Methods and compositions for treating edema refractory to oral diuretics | |
| US12458699B2 (en) | Formulation for oral delivery of proteins, peptides and small molecules with poor permeability | |
| CN112168781B (zh) | 他克莫司的自微乳组合物及其制备方法 | |
| HK1204552B (en) | Solubilized capsule formulation of 1,1-dimethylethyl [(1s)-1-{[(2s,4r)-4-(7-chloro-4methoxyisoquinolin-1-yloxy)-2-({(1r,2s)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}carbamoyl)pyrrolidin-1-yl]carbonyl}-2,2-dimethylpropyl]carbamate | |
| AU2023301386A1 (en) | Pharmaceutical compositions comprising isotretinoin and processes for preparation and uses thereof | |
| HK40012399B (en) | Pharmaceutical formulations of phloroglucinol and trimethylphloroglucinol | |
| HK40012399A (en) | Pharmaceutical formulations of phloroglucinol and trimethylphloroglucinol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |