JP6196154B2 - Ｃ型肝炎ウイルス阻害剤の組み合わせ - Google Patents
Ｃ型肝炎ウイルス阻害剤の組み合わせ Download PDFInfo
- Publication number
- JP6196154B2 JP6196154B2 JP2013523278A JP2013523278A JP6196154B2 JP 6196154 B2 JP6196154 B2 JP 6196154B2 JP 2013523278 A JP2013523278 A JP 2013523278A JP 2013523278 A JP2013523278 A JP 2013523278A JP 6196154 B2 JP6196154 B2 JP 6196154B2
- Authority
- JP
- Japan
- Prior art keywords
- pharmaceutically acceptable
- formula
- acceptable salt
- compound
- hcv
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 241000711549 Hepacivirus C Species 0.000 title description 53
- 239000003112 inhibitor Substances 0.000 title description 20
- 150000001875 compounds Chemical class 0.000 claims description 79
- 150000003839 salts Chemical class 0.000 claims description 57
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 9
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 239000000203 mixture Substances 0.000 description 31
- 238000011282 treatment Methods 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 238000009472 formulation Methods 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- 239000000843 powder Substances 0.000 description 13
- 230000003612 virological effect Effects 0.000 description 13
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 12
- 101800001554 RNA-directed RNA polymerase Proteins 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- -1 NS3 Proteins 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 101800001014 Non-structural protein 5A Proteins 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 101800001838 Serine protease/helicase NS3 Proteins 0.000 description 7
- 230000000840 anti-viral effect Effects 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 201000010099 disease Diseases 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 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 5
- 241000700605 Viruses Species 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 229960000329 ribavirin Drugs 0.000 description 5
- 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 5
- 102000006992 Interferon-alpha Human genes 0.000 description 4
- 108010047761 Interferon-alpha Proteins 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 150000001413 amino acids Chemical group 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000009097 single-agent therapy Methods 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 229940124771 HCV-NS3 protease inhibitor Drugs 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 101800001020 Non-structural protein 4A Proteins 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- 108010076039 Polyproteins Proteins 0.000 description 3
- 108010052090 Renilla Luciferases Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000006072 paste Substances 0.000 description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- NYPIRLYMDJMKGW-VPCXQMTMSA-N 4-amino-1-[(2r,3r,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]pyrimidin-2-one Chemical group 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 2
- 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 2
- 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 2
- 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 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229920001817 Agar Polymers 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 241000710781 Flaviviridae Species 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 108010025815 Kanamycin Kinase Proteins 0.000 description 2
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 108060004795 Methyltransferase Proteins 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- 101800001019 Non-structural protein 4B Proteins 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108700022715 Viral Proteases Proteins 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- 235000012216 bentonite Nutrition 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 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 2
- 229960001418 dasabuvir Drugs 0.000 description 2
- 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 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 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 2
- 239000006260 foam Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 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 2
- 229940097496 nasal spray Drugs 0.000 description 2
- 239000007922 nasal spray Substances 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 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 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000003825 pressing Methods 0.000 description 2
- 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 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 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 2
- 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 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 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 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 239000002691 unilamellar liposome Substances 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-NRXMZTRTSA-N (2r,3r,4r,5s)-2,3,4,5,6-pentahydroxyhexanoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-NRXMZTRTSA-N 0.000 description 1
- CRYXXTXWUCPIMU-WNQIDUERSA-N (2s)-2-aminobutanediamide;phenol Chemical compound OC1=CC=CC=C1.NC(=O)[C@@H](N)CC(N)=O CRYXXTXWUCPIMU-WNQIDUERSA-N 0.000 description 1
- JXDNUMOTWHZSCB-XMTZKCFKSA-N (3s)-3-acetamido-4-[[(2s)-3-carboxy-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1r)-1-carboxy-2-sulfanylethyl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CS)C(O)=O JXDNUMOTWHZSCB-XMTZKCFKSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
- LXFQSRIDYRFTJW-UHFFFAOYSA-M 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=CC(C)=C(S([O-])(=O)=O)C(C)=C1 LXFQSRIDYRFTJW-UHFFFAOYSA-M 0.000 description 1
- OPJKGTJXHVPYIM-UHFFFAOYSA-N 2-methylprop-2-enamide;phenol Chemical compound CC(=C)C(N)=O.OC1=CC=CC=C1 OPJKGTJXHVPYIM-UHFFFAOYSA-N 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N CC(C)(C)[C@@H](C(N(C[C@@H](C1)Oc(nc2)c(cc(cc3)Cl)c3c2OC)[C@@H]1C(N[C@](C1)([C@@H]1C=C)C(NS(C1CC1)(=O)=O)=O)=O)=O)NC(OC(C)(C)C)=O Chemical compound CC(C)(C)[C@@H](C(N(C[C@@H](C1)Oc(nc2)c(cc(cc3)Cl)c3c2OC)[C@@H]1C(N[C@](C1)([C@@H]1C=C)C(NS(C1CC1)(=O)=O)=O)=O)=O)NC(OC(C)(C)C)=O XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108091026890 Coding region Proteins 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
- 208000006558 Dental Calculus Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 241000710188 Encephalomyocarditis virus Species 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-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
- 241000282412 Homo Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 102000008021 Nucleoside-Triphosphatase Human genes 0.000 description 1
- 108010075285 Nucleoside-Triphosphatase Proteins 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229940123066 Polymerase inhibitor Drugs 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108090000944 RNA Helicases Proteins 0.000 description 1
- 102000004409 RNA Helicases Human genes 0.000 description 1
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 238000003349 alamar blue assay Methods 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229920000469 amphiphilic block copolymer Polymers 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 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
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 108700008776 hepatitis C virus NS-5 Proteins 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 244000052637 human pathogen Species 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- UQEIFYRRSNJVDO-UHFFFAOYSA-N n,n-dibenzyl-2-phenylethanamine Chemical compound C=1C=CC=CC=1CN(CC=1C=CC=CC=1)CCC1=CC=CC=C1 UQEIFYRRSNJVDO-UHFFFAOYSA-N 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920002721 polycyanoacrylate Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000004537 potential cytotoxicity Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001915 proofreading effect Effects 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000013102 re-test Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000019204 saccharin Nutrition 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
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000002893 slag Substances 0.000 description 1
- 238000009491 slugging Methods 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical class OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000009264 viral breakthrough Effects 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 230000009265 virologic response Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 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
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4168—1,3-Diazoles having a nitrogen attached in position 2, e.g. clonidine
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- 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
-
- 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
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37139910P | 2010-08-06 | 2010-08-06 | |
| US61/371,399 | 2010-08-06 | ||
| PCT/US2011/046285 WO2012018829A1 (en) | 2010-08-06 | 2011-08-02 | Combinations of hepatitis c virus inhibitors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016072377A Division JP2016155844A (ja) | 2010-08-06 | 2016-03-31 | Ｃ型肝炎ウイルス阻害剤の組み合わせ |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013535487A JP2013535487A (ja) | 2013-09-12 |
| JP2013535487A5 JP2013535487A5 (cg-RX-API-DMAC7.html) | 2014-09-04 |
| JP6196154B2 true JP6196154B2 (ja) | 2017-09-13 |
Family
ID=45559795
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013523278A Expired - Fee Related JP6196154B2 (ja) | 2010-08-06 | 2011-08-02 | Ｃ型肝炎ウイルス阻害剤の組み合わせ |
| JP2016072377A Withdrawn JP2016155844A (ja) | 2010-08-06 | 2016-03-31 | Ｃ型肝炎ウイルス阻害剤の組み合わせ |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016072377A Withdrawn JP2016155844A (ja) | 2010-08-06 | 2016-03-31 | Ｃ型肝炎ウイルス阻害剤の組み合わせ |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US20120196794A1 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2600835B1 (cg-RX-API-DMAC7.html) |
| JP (2) | JP6196154B2 (cg-RX-API-DMAC7.html) |
| KR (1) | KR101846596B1 (cg-RX-API-DMAC7.html) |
| CN (2) | CN105148275A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2011285890B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BR112013002922A2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2807589C (cg-RX-API-DMAC7.html) |
| EA (1) | EA022303B1 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2685174T3 (cg-RX-API-DMAC7.html) |
| IL (1) | IL224369B (cg-RX-API-DMAC7.html) |
| MX (1) | MX2013001170A (cg-RX-API-DMAC7.html) |
| SG (2) | SG187193A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2012018829A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8329159B2 (en) | 2006-08-11 | 2012-12-11 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US20110274648A1 (en) | 2009-11-11 | 2011-11-10 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20110269956A1 (en) | 2009-11-11 | 2011-11-03 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20110281910A1 (en) | 2009-11-12 | 2011-11-17 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US8362020B2 (en) | 2009-12-30 | 2013-01-29 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US20120196794A1 (en) * | 2010-08-06 | 2012-08-02 | Bristol-Myers Squibb Company | Combinations of Hepatitis C Virus Inhibitors |
| EP2963034A1 (en) | 2010-08-26 | 2016-01-06 | RFS Pharma, LLC. | Potent and selective inhibitors of hepatitis c virus |
| US8552047B2 (en) | 2011-02-07 | 2013-10-08 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US9243025B2 (en) * | 2011-03-31 | 2016-01-26 | Idenix Pharmaceuticals, Llc | Compounds and pharmaceutical compositions for the treatment of viral infections |
| US8957203B2 (en) | 2011-05-05 | 2015-02-17 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US9546160B2 (en) | 2011-05-12 | 2017-01-17 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8691757B2 (en) | 2011-06-15 | 2014-04-08 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
| US8492386B2 (en) | 2011-10-21 | 2013-07-23 | Abbvie Inc. | Methods for treating HCV |
| AU2013201406B2 (en) | 2011-10-21 | 2014-10-02 | Abbvie Ireland Unlimited Company | Methods for treating HCV |
| AR088408A1 (es) | 2011-10-21 | 2014-05-28 | Abbvie Inc | Metodos para el tratamiento de hcv |
| US9326973B2 (en) | 2012-01-13 | 2016-05-03 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| DK2909205T3 (en) | 2012-10-19 | 2017-03-06 | Bristol Myers Squibb Co | 9-METHYL-SUBSTITUTED HEXADECAHYDROCYCLOPROPA (E) PYRROL (1,2-A) (1,4) DIAZOCYCLOPENTADECINYLCARBAMATE DERIVATIVES AS NON-STRUCTURAL 3 (NS3) PROTEASE INHIBITORS FOR TREATMENT |
| US9334279B2 (en) | 2012-11-02 | 2016-05-10 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2014070964A1 (en) | 2012-11-02 | 2014-05-08 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| US9643999B2 (en) | 2012-11-02 | 2017-05-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2014070974A1 (en) | 2012-11-05 | 2014-05-08 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| EP2964664B1 (en) | 2013-03-07 | 2017-01-11 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| US20150023913A1 (en) | 2013-07-02 | 2015-01-22 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US9717712B2 (en) | 2013-07-02 | 2017-08-01 | Bristol-Myers Squibb Company | Combinations comprising tricyclohexadecahexaene derivatives for use in the treatment of hepatitis C virus |
| CN105530933B (zh) | 2013-07-17 | 2018-12-11 | 百时美施贵宝公司 | 用于治疗hcv的包含联苯衍生物的组合产品 |
| US10617675B2 (en) | 2015-08-06 | 2020-04-14 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| EA201892448A1 (ru) | 2016-04-28 | 2019-06-28 | Эмори Юниверсити | Алкинсодержащие нуклеотидные и нуклеозидные терапевтические композиции и связанные с ними способы применения |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY140680A (en) * | 2002-05-20 | 2010-01-15 | Bristol Myers Squibb Co | Hepatitis c virus inhibitors |
| US7456166B2 (en) * | 2006-05-17 | 2008-11-25 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| US8329159B2 (en) * | 2006-08-11 | 2012-12-11 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| EP2346329B1 (en) * | 2008-10-09 | 2013-08-21 | Anadys Pharmaceuticals, Inc. | A method of inhibiting hepatitis c virus by combination of a 5,6-dihydro-1h-pyridin-2-one and one or more additional antiviral compounds |
| US8415374B2 (en) * | 2009-10-12 | 2013-04-09 | Bristol-Myers Squibb Company | Combinations of hepatitis C virus inhibitors |
| US20120196794A1 (en) * | 2010-08-06 | 2012-08-02 | Bristol-Myers Squibb Company | Combinations of Hepatitis C Virus Inhibitors |
-
2011
- 2011-08-01 US US13/195,317 patent/US20120196794A1/en not_active Abandoned
- 2011-08-02 EA EA201390155A patent/EA022303B1/ru not_active IP Right Cessation
- 2011-08-02 JP JP2013523278A patent/JP6196154B2/ja not_active Expired - Fee Related
- 2011-08-02 SG SG2013005905A patent/SG187193A1/en unknown
- 2011-08-02 ES ES11815206.5T patent/ES2685174T3/es active Active
- 2011-08-02 CN CN201510608270.5A patent/CN105148275A/zh active Pending
- 2011-08-02 SG SG2014008346A patent/SG2014008346A/en unknown
- 2011-08-02 CN CN201180048188.1A patent/CN103153280B/zh not_active Expired - Fee Related
- 2011-08-02 WO PCT/US2011/046285 patent/WO2012018829A1/en not_active Ceased
- 2011-08-02 BR BR112013002922A patent/BR112013002922A2/pt not_active Application Discontinuation
- 2011-08-02 EP EP11815206.5A patent/EP2600835B1/en not_active Not-in-force
- 2011-08-02 KR KR1020137005628A patent/KR101846596B1/ko not_active Expired - Fee Related
- 2011-08-02 AU AU2011285890A patent/AU2011285890B2/en not_active Ceased
- 2011-08-02 CA CA2807589A patent/CA2807589C/en not_active Expired - Fee Related
- 2011-08-02 MX MX2013001170A patent/MX2013001170A/es unknown
-
2013
- 2013-01-23 IL IL224369A patent/IL224369B/en not_active IP Right Cessation
-
2014
- 2014-04-28 US US14/263,101 patent/US20140235617A1/en not_active Abandoned
-
2015
- 2015-07-31 US US14/814,891 patent/US20150335655A1/en not_active Abandoned
-
2016
- 2016-03-31 JP JP2016072377A patent/JP2016155844A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| AU2011285890A1 (en) | 2013-03-21 |
| KR101846596B1 (ko) | 2018-04-06 |
| EA201390155A1 (ru) | 2013-05-30 |
| CA2807589A1 (en) | 2012-02-09 |
| JP2016155844A (ja) | 2016-09-01 |
| EA022303B1 (ru) | 2015-12-30 |
| BR112013002922A2 (pt) | 2016-06-07 |
| EP2600835A1 (en) | 2013-06-12 |
| KR20140002611A (ko) | 2014-01-08 |
| CN103153280A (zh) | 2013-06-12 |
| MX2013001170A (es) | 2013-02-15 |
| CN105148275A (zh) | 2015-12-16 |
| WO2012018829A1 (en) | 2012-02-09 |
| US20140235617A1 (en) | 2014-08-21 |
| EP2600835B1 (en) | 2018-05-30 |
| IL224369B (en) | 2019-08-29 |
| AU2011285890B2 (en) | 2014-12-18 |
| CA2807589C (en) | 2016-08-30 |
| ES2685174T3 (es) | 2018-10-05 |
| US20120196794A1 (en) | 2012-08-02 |
| SG2014008346A (en) | 2014-05-29 |
| US20150335655A1 (en) | 2015-11-26 |
| SG187193A1 (en) | 2013-03-28 |
| CN103153280B (zh) | 2015-09-09 |
| EP2600835A4 (en) | 2013-11-20 |
| JP2013535487A (ja) | 2013-09-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6196154B2 (ja) | Ｃ型肝炎ウイルス阻害剤の組み合わせ | |
| JP5992828B2 (ja) | Ｃ型肝炎ウイルス阻害剤の組み合わせ | |
| US9060971B2 (en) | Combination pharmaceutical agents as inhibitors of HCV replication | |
| HK1180211A (en) | Combinations of hepatitis c virus inhibitors | |
| HK1180211B (en) | Combinations of hepatitis c virus inhibitors | |
| HK1172237A (en) | Combinations of a specific hcv ns5a inhibitor and an hcv ns3 protease inhibitor | |
| HK1172237B (en) | Combinations of a specific hcv ns5a inhibitor and an hcv ns3 protease inhibitor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140717 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20140717 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20150731 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150804 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20150813 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151102 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20151201 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170817 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6196154 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| LAPS | Cancellation because of no payment of annual fees |