AU2014348762A1 - Formulations of azaindole compounds - Google Patents
Formulations of azaindole compounds Download PDFInfo
- Publication number
- AU2014348762A1 AU2014348762A1 AU2014348762A AU2014348762A AU2014348762A1 AU 2014348762 A1 AU2014348762 A1 AU 2014348762A1 AU 2014348762 A AU2014348762 A AU 2014348762A AU 2014348762 A AU2014348762 A AU 2014348762A AU 2014348762 A1 AU2014348762 A1 AU 2014348762A1
- Authority
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- Australia
- Prior art keywords
- compound
- pharmaceutical composition
- weight
- hcl salt
- combination
- 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.)
- Abandoned
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- 239000000203 mixture Substances 0.000 title claims abstract description 220
- 238000009472 formulation Methods 0.000 title description 18
- 125000005334 azaindolyl group Chemical class N1N=C(C2=CC=CC=C12)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 644
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 320
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 151
- 238000000034 method Methods 0.000 claims abstract description 103
- 239000000945 filler Substances 0.000 claims abstract description 96
- 206010022000 influenza Diseases 0.000 claims abstract description 85
- 241000712461 unidentified influenza virus Species 0.000 claims abstract description 47
- 238000002156 mixing Methods 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 239000003002 pH adjusting agent Substances 0.000 claims abstract description 15
- 230000010076 replication Effects 0.000 claims abstract description 12
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 9
- -1 polyplasdone Polymers 0.000 claims description 440
- 150000003840 hydrochlorides Chemical class 0.000 claims description 174
- 239000011230 binding agent Substances 0.000 claims description 79
- 239000003795 chemical substances by application Substances 0.000 claims description 74
- 239000007884 disintegrant Substances 0.000 claims description 74
- 239000008187 granular material Substances 0.000 claims description 68
- 239000000314 lubricant Substances 0.000 claims description 68
- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 claims description 54
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 50
- 229960003752 oseltamivir Drugs 0.000 claims description 46
- 239000003814 drug Substances 0.000 claims description 42
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 41
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 39
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 39
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 35
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 32
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 32
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- 229960001375 lactose Drugs 0.000 claims description 27
- 239000008101 lactose Substances 0.000 claims description 27
- 229910052751 metal Inorganic materials 0.000 claims description 27
- 239000002184 metal Substances 0.000 claims description 27
- 229920002472 Starch Polymers 0.000 claims description 25
- 235000019698 starch Nutrition 0.000 claims description 25
- 229940124597 therapeutic agent Drugs 0.000 claims description 25
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 23
- 238000005469 granulation Methods 0.000 claims description 23
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 23
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 23
- 229940032147 starch Drugs 0.000 claims description 21
- 239000008107 starch Substances 0.000 claims description 21
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 19
- 229920000858 Cyclodextrin Polymers 0.000 claims description 19
- 229960001028 zanamivir Drugs 0.000 claims description 19
- ARAIBEBZBOPLMB-UFGQHTETSA-N zanamivir Chemical compound CC(=O)N[C@@H]1[C@@H](N=C(N)N)C=C(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO ARAIBEBZBOPLMB-UFGQHTETSA-N 0.000 claims description 19
- 229940079593 drug Drugs 0.000 claims description 18
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 18
- 239000000080 wetting agent Substances 0.000 claims description 17
- 239000004359 castor oil Substances 0.000 claims description 16
- 235000000346 sugar Nutrition 0.000 claims description 15
- 239000008139 complexing agent Substances 0.000 claims description 14
- 229920000136 polysorbate Polymers 0.000 claims description 14
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 13
- 229960004853 betadex Drugs 0.000 claims description 13
- 235000019438 castor oil Nutrition 0.000 claims description 13
- 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 claims description 13
- 229910019142 PO4 Inorganic materials 0.000 claims description 12
- 239000006172 buffering agent Substances 0.000 claims description 12
- 235000010980 cellulose Nutrition 0.000 claims description 12
- 229920002678 cellulose Polymers 0.000 claims description 12
- 230000003179 granulation Effects 0.000 claims description 12
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 11
- MHQJUHSHQGQVTM-HNENSFHCSA-N Octadecyl fumarate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)\C=C/C(O)=O MHQJUHSHQGQVTM-HNENSFHCSA-N 0.000 claims description 11
- 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 claims description 11
- 229940071138 stearyl fumarate Drugs 0.000 claims description 11
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 claims description 10
- 229960005168 croscarmellose Drugs 0.000 claims description 10
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 claims description 10
- 238000000338 in vitro Methods 0.000 claims description 10
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 10
- 239000001488 sodium phosphate Substances 0.000 claims description 10
- 239000001116 FEMA 4028 Substances 0.000 claims description 9
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 9
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 9
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 9
- 239000001913 cellulose Substances 0.000 claims description 9
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 9
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 9
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 9
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 9
- 235000019359 magnesium stearate Nutrition 0.000 claims description 9
- 239000010452 phosphate Substances 0.000 claims description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 9
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 9
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 9
- 239000002911 sialidase inhibitor Substances 0.000 claims description 9
- 239000011734 sodium Substances 0.000 claims description 9
- 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 claims description 8
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 8
- 241000712431 Influenza A virus Species 0.000 claims description 8
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 8
- 229960000913 crospovidone Drugs 0.000 claims description 8
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 8
- 229960001021 lactose monohydrate Drugs 0.000 claims description 8
- 229910052708 sodium Inorganic materials 0.000 claims description 8
- 239000001506 calcium phosphate Substances 0.000 claims description 7
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 7
- 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 claims description 7
- 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 claims description 6
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 6
- 235000011010 calcium phosphates Nutrition 0.000 claims description 6
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 6
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 6
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 6
- 235000010356 sorbitol Nutrition 0.000 claims description 6
- 229940071117 starch glycolate Drugs 0.000 claims description 6
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 6
- 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 claims description 5
- 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 claims description 5
- 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 claims description 5
- 229940123066 Polymerase inhibitor Drugs 0.000 claims description 5
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 5
- 229950008882 polysorbate Drugs 0.000 claims description 5
- 229920003109 sodium starch glycolate Polymers 0.000 claims description 5
- 239000008109 sodium starch glycolate Substances 0.000 claims description 5
- 229940079832 sodium starch glycolate Drugs 0.000 claims description 5
- 239000000600 sorbitol Substances 0.000 claims description 5
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 5
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 claims description 4
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 claims description 4
- 229940123424 Neuraminidase inhibitor Drugs 0.000 claims description 4
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 claims description 4
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- 230000002155 anti-virotic effect Effects 0.000 claims description 4
- 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 claims description 4
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 4
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 4
- 235000019800 disodium phosphate Nutrition 0.000 claims description 4
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 claims description 4
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- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 4
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 4
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 4
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 4
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- 239000008121 dextrose Substances 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
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- 239000000243 solution Substances 0.000 description 85
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- 230000004083 survival effect Effects 0.000 description 18
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- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 18
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- A61P31/12—Antivirals
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- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Veterinary Medicine (AREA)
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- Inorganic Chemistry (AREA)
- Emergency Medicine (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| PCT/US2014/065144 WO2015073491A1 (en) | 2013-11-13 | 2014-11-12 | Formulations of azaindole compounds |
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| SG10201405826RA (en) | 2009-06-17 | 2014-12-30 | Vertex Pharma | Inhibitors of influenza viruses replication |
| UA118010C2 (uk) | 2011-08-01 | 2018-11-12 | Вертекс Фармасьютікалз Інкорпорейтед | Інгібітори реплікації вірусів грипу |
| PT3068776T (pt) | 2013-11-13 | 2019-08-26 | Vertex Pharma | Inibidores da replicação de vírus da gripe |
| WO2015073481A1 (en) | 2013-11-13 | 2015-05-21 | Vertex Pharmaceuticals Incorporated | Methods of preparing inhibitors of influenza viruses replication |
| JP6704416B2 (ja) | 2015-05-13 | 2020-06-03 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | インフルエンザウイルスの複製の阻害剤を調製する方法 |
| EP3294735B8 (en) | 2015-05-13 | 2022-01-05 | Vertex Pharmaceuticals Incorporated | Inhibitors of influenza viruses replication |
| AU2016368317B2 (en) | 2015-12-09 | 2019-05-23 | Sunshine Lake Pharma Co., Ltd. | Inhibitors of influenza virus replication, application methods and uses thereof |
| CN107759571B (zh) | 2016-08-16 | 2021-03-02 | 广东东阳光药业有限公司 | 流感病毒复制抑制剂及其使用方法和用途 |
| CN109641868B (zh) | 2016-08-30 | 2021-12-03 | 广东东阳光药业有限公司 | 流感病毒复制抑制剂及其使用方法和用途 |
| US10987354B2 (en) | 2016-12-15 | 2021-04-27 | Sunshine Lake Pharma Co., Ltd. | Inhibitors of influenza virus replication and uses thereof |
| WO2018127096A1 (en) | 2017-01-05 | 2018-07-12 | Sunshine Lake Pharma Co., Ltd. | Inhibitors of influenza virus replication and uses thereof |
| WO2018137670A1 (zh) * | 2017-01-24 | 2018-08-02 | 苏州科睿思制药有限公司 | 一种病毒蛋白抑制剂药物vx-787的晶型及其制备方法和用途 |
| CN110446711B (zh) | 2017-03-02 | 2022-02-15 | 广东东阳光药业有限公司 | 流感病毒复制抑制剂及其用途 |
| CA3059362A1 (en) * | 2017-04-12 | 2018-10-18 | Vertex Pharmaceuticals Incorporated | Combination therapies for treating influenza virus infection |
| JP7175966B2 (ja) * | 2017-08-31 | 2022-11-21 | ノバルティス アーゲー | 顆粒剤を調製する方法 |
| CN111936497A (zh) * | 2018-04-06 | 2020-11-13 | 杨森制药公司 | 制备匹莫迪韦盐酸盐半水合物的结晶形式的等温反应性结晶方法 |
| WO2020058745A1 (en) * | 2018-09-18 | 2020-03-26 | Shionogi & Co., Ltd. | Treating influenza using substituted polycyclic pyridone derivatives and prodrugs thereof |
| CN113164612A (zh) | 2018-11-13 | 2021-07-23 | 共晶制药公司 | 流感治疗剂的配制物 |
| KR20200106607A (ko) * | 2019-03-05 | 2020-09-15 | 주식회사 코아팜바이오 | 오셀타미비르 함유 의약 조성물 |
| WO2020256820A1 (en) * | 2019-06-20 | 2020-12-24 | Janssen Pharmaceuticals, Inc. | Formulations of azaindole compounds |
| CN112578034B (zh) * | 2020-11-04 | 2022-02-11 | 广东众生睿创生物科技有限公司 | 一种手性胺小分子及其盐的质量控制方法 |
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| LT2522365T (lt) * | 2004-11-24 | 2017-02-10 | Meda Pharmaceuticals Inc. | Kompozicijos, apimančios azelastiną, ir jų panaudojimo būdai |
| US20120093738A1 (en) * | 2009-06-11 | 2012-04-19 | Rubicon Research Private Limited | Taste-masked oral formulations of influenza antivirals |
| SG10201405826RA (en) * | 2009-06-17 | 2014-12-30 | Vertex Pharma | Inhibitors of influenza viruses replication |
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2014
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- 2014-11-12 CN CN201480071163.7A patent/CN105848683A/zh active Pending
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2016
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2018
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2020
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2021
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| SG10201804024VA (en) | 2018-07-30 |
| CA2930105A1 (en) | 2015-05-21 |
| JP2016537347A (ja) | 2016-12-01 |
| MX2016006197A (es) | 2016-08-08 |
| US20180318301A1 (en) | 2018-11-08 |
| JP2021191796A (ja) | 2021-12-16 |
| WO2015073491A1 (en) | 2015-05-21 |
| KR20160084465A (ko) | 2016-07-13 |
| IL278214A (en) | 2020-11-30 |
| RU2685730C1 (ru) | 2019-04-23 |
| EP3068434A1 (en) | 2016-09-21 |
| IL245587A0 (en) | 2016-06-30 |
| US20160250213A1 (en) | 2016-09-01 |
| US20210008072A1 (en) | 2021-01-14 |
| CN105848683A (zh) | 2016-08-10 |
| CL2016001111A1 (es) | 2017-06-09 |
| RU2016122609A (ru) | 2017-12-18 |
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