CA2798386A1 - Pharmaceutical compositions and methods of making same - Google Patents
Pharmaceutical compositions and methods of making same Download PDFInfo
- Publication number
- CA2798386A1 CA2798386A1 CA2798386A CA2798386A CA2798386A1 CA 2798386 A1 CA2798386 A1 CA 2798386A1 CA 2798386 A CA2798386 A CA 2798386A CA 2798386 A CA2798386 A CA 2798386A CA 2798386 A1 CA2798386 A1 CA 2798386A1
- Authority
- CA
- Canada
- Prior art keywords
- pharmaceutical composition
- cyclodextrin
- pazopanib
- dnm
- composition according
- 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
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 74
- 238000000034 method Methods 0.000 title claims abstract description 47
- 239000000203 mixture Substances 0.000 claims abstract description 126
- 229960000639 pazopanib Drugs 0.000 claims abstract description 119
- 239000003798 L01XE11 - Pazopanib Substances 0.000 claims abstract description 116
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 claims abstract description 114
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class 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 abstract description 84
- 239000000243 solution Substances 0.000 claims description 95
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 75
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 66
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 58
- 238000009472 formulation Methods 0.000 claims description 34
- 238000002360 preparation method Methods 0.000 claims description 30
- 239000003795 chemical substances by application Substances 0.000 claims description 28
- 239000006172 buffering agent Substances 0.000 claims description 20
- 239000003002 pH adjusting agent Substances 0.000 claims description 19
- MQHIQUBXFFAOMK-UHFFFAOYSA-N pazopanib hydrochloride Chemical group Cl.C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 MQHIQUBXFFAOMK-UHFFFAOYSA-N 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000003889 eye drop Substances 0.000 claims description 13
- -1 methyl- Chemical group 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 10
- 239000012047 saturated solution Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 5
- 229960005492 pazopanib hydrochloride Drugs 0.000 claims description 5
- 239000010452 phosphate Substances 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- DZLKUJDRGIBINH-ZMGQIDSOSA-N 4-[[(1S,3R,5R,6S,8R,10R,11S,13R,15R,16S,18R,20R,21S,23R,25R,26S,28R,30R,31S,33R,35R,36R,37R,38R,39R,40R,41R,42R,43R,44R,45R,46R,47R,48R,49R)-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecahydroxy-10,15,20,25,30,35-hexakis(4-sulfobutoxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontan-5-yl]methoxy]butane-1-sulfonic acid Chemical compound O([C@@H]([C@@H]([C@H]1O)O)O[C@H]2[C@H](O)[C@H]([C@@H](O[C@@H]3[C@@H](COCCCCS(O)(=O)=O)O[C@@H]([C@@H]([C@H]3O)O)O[C@@H]3[C@@H](COCCCCS(O)(=O)=O)O[C@@H]([C@@H]([C@H]3O)O)O[C@@H]3[C@@H](COCCCCS(O)(=O)=O)O[C@@H]([C@@H]([C@H]3O)O)O[C@@H]3[C@@H](COCCCCS(O)(=O)=O)O[C@@H]([C@@H]([C@H]3O)O)O3)O[C@@H]2COCCCCS(O)(=O)=O)O)[C@H](COCCCCS(O)(=O)=O)[C@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H]3[C@@H](COCCCCS(O)(=O)=O)O1 DZLKUJDRGIBINH-ZMGQIDSOSA-N 0.000 claims 11
- 229940031576 hydroxypropylbetadex (0.58-0.68 ms) Drugs 0.000 claims 5
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 4
- 229920000858 Cyclodextrin Polymers 0.000 description 47
- 229960004853 betadex Drugs 0.000 description 38
- 238000004448 titration Methods 0.000 description 38
- 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 description 37
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 34
- 235000002639 sodium chloride Nutrition 0.000 description 28
- 239000002245 particle Substances 0.000 description 26
- 239000000523 sample Substances 0.000 description 24
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 23
- 239000003814 drug Substances 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
- 239000012086 standard solution Substances 0.000 description 21
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
- 229940079593 drug Drugs 0.000 description 20
- NZAQRZWBQUIBSF-UHFFFAOYSA-N 4-(4-sulfobutoxy)butane-1-sulfonic acid Chemical compound OS(=O)(=O)CCCCOCCCCS(O)(=O)=O NZAQRZWBQUIBSF-UHFFFAOYSA-N 0.000 description 19
- 239000012088 reference solution Substances 0.000 description 17
- 239000011780 sodium chloride Substances 0.000 description 16
- 239000011521 glass Substances 0.000 description 15
- 239000002997 ophthalmic solution Substances 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 13
- 239000012488 sample solution Substances 0.000 description 12
- 239000005711 Benzoic acid Substances 0.000 description 11
- 235000010233 benzoic acid Nutrition 0.000 description 11
- 238000004364 calculation method Methods 0.000 description 11
- 238000007792 addition Methods 0.000 description 10
- 229910052786 argon Inorganic materials 0.000 description 10
- 229940097362 cyclodextrins Drugs 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 238000003918 potentiometric titration Methods 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 239000007789 gas Substances 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 229940054534 ophthalmic solution Drugs 0.000 description 8
- 238000005063 solubilization Methods 0.000 description 8
- 230000007928 solubilization Effects 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000010668 complexation reaction Methods 0.000 description 7
- 239000012458 free base Substances 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- VSDUZFOSJDMAFZ-VIFPVBQESA-N methyl L-phenylalaninate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-VIFPVBQESA-N 0.000 description 6
- 239000008363 phosphate buffer Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000003860 storage Methods 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000008215 water for injection Substances 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 229940088679 drug related substance Drugs 0.000 description 4
- 239000001488 sodium phosphate Substances 0.000 description 4
- 229910000162 sodium phosphate Inorganic materials 0.000 description 4
- 235000011008 sodium phosphates Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000011200 topical administration Methods 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 229940012356 eye drops Drugs 0.000 description 3
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000010979 pH adjustment Methods 0.000 description 3
- 239000013618 particulate matter Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 231100001271 preclinical toxicology Toxicity 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000012453 solvate Substances 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
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 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 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 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 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
- 206010064930 age-related macular degeneration Diseases 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- 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 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 2
- 229940097267 cobaltous chloride Drugs 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 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
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- IDIIJJHBXUESQI-DFIJPDEKSA-N moxifloxacin hydrochloride Chemical compound Cl.COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 IDIIJJHBXUESQI-DFIJPDEKSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- NMMVKSMGBDRONO-UHFFFAOYSA-N potassium;9-methyl-3-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound [K+].CC1=CC=CN(C2=O)C1=NC=C2C1=NN=N[N-]1 NMMVKSMGBDRONO-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- BBMHARZCALWXSL-UHFFFAOYSA-M sodium dihydrogenphosphate monohydrate Chemical compound O.[Na+].OP(O)([O-])=O BBMHARZCALWXSL-UHFFFAOYSA-M 0.000 description 2
- GNMBMOULKUXEQF-UHFFFAOYSA-M sodium;2-(3-fluoro-4-phenylphenyl)propanoate;dihydrate Chemical compound O.O.[Na+].FC1=CC(C(C([O-])=O)C)=CC=C1C1=CC=CC=C1 GNMBMOULKUXEQF-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008137 solubility enhancer Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- MKPLKVHSHYCHOC-AHTXBMBWSA-N travoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(C(F)(F)F)=C1 MKPLKVHSHYCHOC-AHTXBMBWSA-N 0.000 description 2
- 239000012976 trial formulation Substances 0.000 description 2
- 238000010200 validation analysis Methods 0.000 description 2
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- WLRMANUAADYWEA-NWASOUNVSA-N (S)-timolol maleate Chemical compound OC(=O)\C=C/C(O)=O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 WLRMANUAADYWEA-NWASOUNVSA-N 0.000 description 1
- IWEGDQUCWQFKHS-UHFFFAOYSA-N 1-(1,3-dioxolan-2-ylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(CC2OCCO2)N=C1 IWEGDQUCWQFKHS-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- VCCRYTPIYXGSRM-UHFFFAOYSA-N 5-[[4-[(2,3-dimethylindazol-6-yl)methylamino]pyrimidin-2-yl]amino]-2-methylbenzenesulfonamide;hydrate;hydrochloride Chemical compound O.Cl.C1=CC2=C(C)N(C)N=C2C=C1CNC(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 VCCRYTPIYXGSRM-UHFFFAOYSA-N 0.000 description 1
- ZLOLCGXDJBXQCN-UHFFFAOYSA-N 5-[[4-[(2,3-dimethylindazol-6-yl)methylamino]pyrimidin-2-yl]amino]-2-methylbenzenesulfonamide;hydrochloride Chemical compound Cl.C1=CC2=C(C)N(C)N=C2C=C1CNC(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 ZLOLCGXDJBXQCN-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 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
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
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- Inorganic Chemistry (AREA)
- Ophthalmology & Optometry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Molecular Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
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| US33171510P | 2010-05-05 | 2010-05-05 | |
| US61/331,715 | 2010-05-05 | ||
| PCT/US2011/035363 WO2011140343A1 (en) | 2010-05-05 | 2011-05-05 | Pharmaceutical compositions and methods of making same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2798386A1 true CA2798386A1 (en) | 2011-11-10 |
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| CA2798386A Abandoned CA2798386A1 (en) | 2010-05-05 | 2011-05-05 | Pharmaceutical compositions and methods of making same |
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| JP (1) | JP5835717B2 (https=) |
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| CN (1) | CN102970871A (https=) |
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| BR (1) | BR112012028291A2 (https=) |
| CA (1) | CA2798386A1 (https=) |
| CL (1) | CL2012003075A1 (https=) |
| CO (1) | CO6640262A2 (https=) |
| CR (1) | CR20120556A (https=) |
| DO (1) | DOP2012000281A (https=) |
| EA (1) | EA201291168A1 (https=) |
| ES (1) | ES2519615T3 (https=) |
| IL (1) | IL222751A0 (https=) |
| MA (1) | MA34286B1 (https=) |
| MX (1) | MX2012012837A (https=) |
| NZ (1) | NZ603411A (https=) |
| PE (1) | PE20130217A1 (https=) |
| PH (1) | PH12012502159A1 (https=) |
| SG (1) | SG185087A1 (https=) |
| TW (1) | TW201206908A (https=) |
| UY (1) | UY33367A (https=) |
| WO (1) | WO2011140343A1 (https=) |
| ZA (1) | ZA201208265B (https=) |
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| US20070020299A1 (en) | 2003-12-31 | 2007-01-25 | Pipkin James D | Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid |
| ES2493641T3 (es) * | 2007-06-28 | 2014-09-12 | Cydex Pharmaceuticals, Inc. | Administración nasal de soluciones acuosas de corticosteroides |
| US12370352B2 (en) | 2007-06-28 | 2025-07-29 | Cydex Pharmaceuticals, Inc. | Nasal and ophthalmic delivery of aqueous corticosteroid solutions |
| US8623395B2 (en) | 2010-01-29 | 2014-01-07 | Forsight Vision4, Inc. | Implantable therapeutic device |
| WO2013022801A1 (en) | 2011-08-05 | 2013-02-14 | Forsight Vision4, Inc. | Small molecule delivery with implantable therapeutic device |
| AR081364A1 (es) * | 2010-05-05 | 2012-08-29 | Glaxo Wellcome Mfg Pte Ltd | Composiciones farmaceuticas de pazopanib y metodos para su elaboracion |
| EP3861969A1 (en) | 2010-08-05 | 2021-08-11 | ForSight Vision4, Inc. | Injector apparatus for drug delivery |
| WO2012068549A2 (en) | 2010-11-19 | 2012-05-24 | Forsight Vision4, Inc. | Therapeutic agent formulations for implanted devices |
| PT2755600T (pt) | 2011-09-16 | 2021-04-19 | Forsight Vision4 Inc | Aparelhos de troca de fluidos |
| AU2013221298A1 (en) * | 2012-02-17 | 2014-08-28 | Pharmacyclics Llc | Combinations of histone deacetylase inhibitor and pazopanib and uses thereof |
| CN110062479A (zh) * | 2012-03-08 | 2019-07-26 | 三星电子株式会社 | 用于控制无线通信系统中的服务的方法 |
| WO2014152959A1 (en) * | 2013-03-14 | 2014-09-25 | Forsight Vision4, Inc. | Systems for sustained intraocular delivery of low solubility compounds from a port delivery system implant |
| CN105246438B (zh) | 2013-03-28 | 2018-01-26 | 弗赛特影像4股份有限公司 | 用于输送治疗物质的眼科植入物 |
| ES2813877T3 (es) | 2013-08-28 | 2021-03-25 | Crown Bioscience Inc Taicang | Distintivos de expresión génica predictivos de la respuesta de un sujeto a un inhibidor multicinasa y métodos de uso de los mismos |
| RU2017105844A (ru) * | 2014-08-08 | 2018-09-11 | Форсайт Вижн4, Инк. | Стабильные и растворимые составы ингибиторов рецепторных тирозинкиназ и способы их получения |
| CN110478119B (zh) | 2014-11-10 | 2022-04-15 | 弗赛特影像4股份有限公司 | 可膨胀药物递送装置和使用方法 |
| JP6818264B2 (ja) | 2014-12-25 | 2021-01-20 | 国立大学法人京都大学 | 高密度リポタンパク質およびその細胞親和性ペプチドを融合した高密度リポタンパク質の点眼による後眼部薬物デリバリー |
| CN113017981B (zh) | 2016-04-05 | 2023-07-25 | 弗赛特影像4股份有限公司 | 药物递送装置 |
| WO2018192416A1 (en) * | 2017-04-17 | 2018-10-25 | National Institute Of Biological Sciences, Beijing | Treating Male Senescence |
| WO2019028104A1 (en) * | 2017-08-02 | 2019-02-07 | Alphala Co., Ltd. | NOVEL COMPOUND AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME |
| EP4249069B1 (en) * | 2018-06-07 | 2025-11-19 | Pfizer Inc. | Aqueous formulation comprising 1-(4-{[4-(dimethylamino)piperidin-1-yl]carbonyl}phenyl)-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea |
| CN113350351A (zh) * | 2020-03-13 | 2021-09-07 | 青晓制药公司 | 帕唑帕尼的应用、药物组合物、注射液及制备方法和应用 |
| USD1033637S1 (en) | 2022-01-24 | 2024-07-02 | Forsight Vision4, Inc. | Fluid exchange device |
| US20240050429A1 (en) * | 2022-08-10 | 2024-02-15 | Qx Therapeutics, Inc. | Pazopanib pharmaceutical composition, injection and preparation method and use thereof |
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| SE8904296D0 (sv) * | 1989-12-21 | 1989-12-21 | Pharmacia Ab | Transdermal system |
| US7893040B2 (en) * | 2005-07-22 | 2011-02-22 | Oculis Ehf | Cyclodextrin nanotechnology for ophthalmic drug delivery |
| EA016227B1 (ru) * | 2005-11-29 | 2012-03-30 | Смитклайн Бичем Корпорейшн | Способ лечения офтальмологических неоваскулярных расстройств |
| AR059066A1 (es) * | 2006-01-27 | 2008-03-12 | Amgen Inc | Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf) |
| MX2008013405A (es) * | 2006-04-18 | 2009-03-09 | Ekr Therapeutics Inc | Composiciones farmaceuticas premezcladas listas para uso. |
| ES2830024T3 (es) * | 2007-10-19 | 2021-06-02 | Novartis Ag | Composiciones y métodos para el tratamiento del edema macular |
| US8987280B2 (en) * | 2008-01-30 | 2015-03-24 | Genentech, Inc. | Pyrazolopyrimidine PI3K inhibitor compounds and methods of use |
| AU2010273254A1 (en) * | 2009-07-16 | 2012-02-02 | Glaxo Wellcome Manufacturing Pte Ltd | Treatment method |
| US20120232102A1 (en) * | 2009-09-30 | 2012-09-13 | Chun-Fang Xu | Methods Of Administration And Treatment |
| UY33164A (es) * | 2010-01-06 | 2011-08-31 | Glaxo Wellcome Mfg Pte Ltd | Metodo de tratamiento |
| US20130023550A1 (en) * | 2010-05-05 | 2013-01-24 | Glaxo Wellcome Manufacturing Pte, Ltd | Pharmaceutical compositions and methods of making same |
| AR081364A1 (es) * | 2010-05-05 | 2012-08-29 | Glaxo Wellcome Mfg Pte Ltd | Composiciones farmaceuticas de pazopanib y metodos para su elaboracion |
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2011
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- 2011-05-03 UY UY0001033367A patent/UY33367A/es unknown
- 2011-05-03 TW TW100115488A patent/TW201206908A/zh unknown
- 2011-05-05 PH PH1/2012/502159A patent/PH12012502159A1/en unknown
- 2011-05-05 CN CN2011800333447A patent/CN102970871A/zh active Pending
- 2011-05-05 MX MX2012012837A patent/MX2012012837A/es active IP Right Grant
- 2011-05-05 KR KR1020127031739A patent/KR20130071434A/ko not_active Withdrawn
- 2011-05-05 CA CA2798386A patent/CA2798386A1/en not_active Abandoned
- 2011-05-05 NZ NZ603411A patent/NZ603411A/en not_active IP Right Cessation
- 2011-05-05 JP JP2013509268A patent/JP5835717B2/ja not_active Expired - Fee Related
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- 2011-05-05 MA MA35417A patent/MA34286B1/fr unknown
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- 2011-05-05 US US13/101,689 patent/US20110281901A1/en not_active Abandoned
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2012
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2015
- 2015-05-06 US US14/705,298 patent/US20150231265A1/en not_active Abandoned
Also Published As
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|---|---|
| KR20130071434A (ko) | 2013-06-28 |
| TW201206908A (en) | 2012-02-16 |
| PH12012502159A1 (en) | 2013-02-04 |
| JP2013525501A (ja) | 2013-06-20 |
| AU2011247995A1 (en) | 2012-12-13 |
| DOP2012000281A (es) | 2013-05-31 |
| PE20130217A1 (es) | 2013-03-21 |
| CN102970871A (zh) | 2013-03-13 |
| JP5835717B2 (ja) | 2015-12-24 |
| SG185087A1 (en) | 2012-12-28 |
| AR081364A1 (es) | 2012-08-29 |
| IL222751A0 (en) | 2012-12-31 |
| US20150231265A1 (en) | 2015-08-20 |
| MA34286B1 (fr) | 2013-06-01 |
| CR20120556A (es) | 2013-02-20 |
| UY33367A (es) | 2011-10-31 |
| US20120028918A1 (en) | 2012-02-02 |
| EP2566331B1 (en) | 2014-09-03 |
| EP2566331A1 (en) | 2013-03-13 |
| WO2011140343A1 (en) | 2011-11-10 |
| ZA201208265B (en) | 2013-07-31 |
| CL2012003075A1 (es) | 2013-03-08 |
| EP2566331A4 (en) | 2013-09-18 |
| HK1175947A1 (en) | 2013-07-19 |
| BR112012028291A2 (pt) | 2015-09-15 |
| AU2011247995B2 (en) | 2014-07-31 |
| EA201291168A1 (ru) | 2013-06-28 |
| MX2012012837A (es) | 2013-01-24 |
| CO6640262A2 (es) | 2013-03-22 |
| NZ603411A (en) | 2014-10-31 |
| US20110281901A1 (en) | 2011-11-17 |
| ES2519615T3 (es) | 2014-11-07 |
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Legal Events
| Date | Code | Title | Description |
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| FZDE | Discontinued |
Effective date: 20170505 |