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 |
Family
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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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| ZA (1) | ZA201208265B (enExample) |
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| US20070020299A1 (en) | 2003-12-31 | 2007-01-25 | Pipkin James D | Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid |
| US12370352B2 (en) | 2007-06-28 | 2025-07-29 | Cydex Pharmaceuticals, Inc. | Nasal and ophthalmic delivery of aqueous corticosteroid solutions |
| ES2493641T3 (es) * | 2007-06-28 | 2014-09-12 | Cydex Pharmaceuticals, Inc. | Administración nasal de soluciones acuosas de corticosteroides |
| US8623395B2 (en) | 2010-01-29 | 2014-01-07 | Forsight Vision4, Inc. | Implantable therapeutic device |
| UY33367A (es) * | 2010-05-05 | 2011-10-31 | Glaxo Wellcome Mfg Pte Ltd | Composiciones farmacéuticas y métodos para su elaboración |
| HUE054113T2 (hu) | 2010-08-05 | 2021-08-30 | Forsight Vision4 Inc | Injekciós készülék gyógyszerbejuttatáshoz |
| WO2012068549A2 (en) | 2010-11-19 | 2012-05-24 | Forsight Vision4, Inc. | Therapeutic agent formulations for implanted devices |
| EP2739252A4 (en) | 2011-08-05 | 2015-08-12 | Forsight Vision4 Inc | SMALL MOLECULE ADMINISTRATION USING AN IMPLANTABLE THERAPEUTIC DEVICE |
| WO2013040247A2 (en) | 2011-09-16 | 2013-03-21 | Forsight Vision4, Inc. | Fluid exchange apparatus and methods |
| RU2014137190A (ru) * | 2012-02-17 | 2016-04-10 | Фармасайкликс, Инк. | Комбинации ингибитора гистон-деацетилазы и пазопаниба и их применение |
| EP2824981B1 (en) * | 2012-03-08 | 2019-02-27 | Samsung Electronics Co., Ltd. | Method for controlling service in radio communication system |
| US9968603B2 (en) | 2013-03-14 | 2018-05-15 | Forsight Vision4, Inc. | Systems for sustained intraocular delivery of low solubility compounds from a port delivery system implant |
| EP2978393B1 (en) | 2013-03-28 | 2023-12-27 | ForSight Vision4, Inc. | Ophthalmic implant for delivering therapeutic substances |
| EP3039424B1 (en) | 2013-08-28 | 2020-07-29 | Crown Bioscience, Inc. (Taicang) | Gene expression signatures predictive of subject response to a multi-kinase inhibitor and methods of using the same |
| MY182793A (en) * | 2014-08-08 | 2021-02-05 | Forsight Vision4 Inc | Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof |
| AU2015346450B2 (en) | 2014-11-10 | 2020-01-30 | Forsight Vision4, Inc. | Expandable drug delivery devices and method of use |
| EP3238746B1 (en) | 2014-12-25 | 2023-12-20 | Kyoto University | High-density lipoprotein, and delivery of drug to posterior segment of eye by ocular instillation of said cytophilic peptide-fused high-density lipoprotein |
| KR20180133440A (ko) | 2016-04-05 | 2018-12-14 | 포사이트 비젼4, 인크. | 이식 가능한 안구 약물 전달 장치 |
| CN110769853B (zh) * | 2017-04-17 | 2022-06-03 | 北京生命科学研究所 | 治疗雄性衰老 |
| WO2019028104A1 (en) * | 2017-08-02 | 2019-02-07 | Alphala Co., Ltd. | NOVEL COMPOUND AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME |
| EP3810089B1 (en) * | 2018-06-07 | 2023-08-02 | 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 |
| KR20080071188A (ko) * | 2005-11-29 | 2008-08-01 | 스미스클라인 비참 코포레이션 | 치료 방법 |
| 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) |
| CN101484136A (zh) * | 2006-04-18 | 2009-07-15 | Ekr治疗公司 | 预混合的、立即可用的药物组合物 |
| MX2010004281A (es) * | 2007-10-19 | 2010-09-10 | Sarcode Corp | Composiciones y metodos para el tratamiento de la retinopatia diabetica. |
| ES2494365T3 (es) * | 2008-01-30 | 2014-09-15 | Genentech, Inc. | Compuestos de pirazolopirimidina que inhiben PI3K y métodos de uso |
| WO2011009016A1 (en) * | 2009-07-16 | 2011-01-20 | Glaxo Wellcome Manufacturing Pte Ltd | Treatment method |
| WO2011039648A1 (en) * | 2009-09-30 | 2011-04-07 | Glaxo Wellcome Manufacturing Pte Ltd. | Methods of administration and treatment |
| UY33164A (es) * | 2010-01-06 | 2011-08-31 | Glaxo Wellcome Mfg Pte Ltd | Metodo de tratamiento |
| UY33367A (es) * | 2010-05-05 | 2011-10-31 | Glaxo Wellcome Mfg Pte Ltd | Composiciones farmacéuticas y métodos para su elaboración |
| US20130023550A1 (en) * | 2010-05-05 | 2013-01-24 | Glaxo Wellcome Manufacturing Pte, Ltd | Pharmaceutical compositions and methods of making same |
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2011
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- 2011-05-03 TW TW100115488A patent/TW201206908A/zh unknown
- 2011-05-03 AR ARP110101514A patent/AR081364A1/es unknown
- 2011-05-05 PE PE2012002115A patent/PE20130217A1/es not_active Application Discontinuation
- 2011-05-05 US US13/101,689 patent/US20110281901A1/en not_active Abandoned
- 2011-05-05 PH PH1/2012/502159A patent/PH12012502159A1/en unknown
- 2011-05-05 MA MA35417A patent/MA34286B1/fr unknown
- 2011-05-05 JP JP2013509268A patent/JP5835717B2/ja not_active Expired - Fee Related
- 2011-05-05 CA CA2798386A patent/CA2798386A1/en not_active Abandoned
- 2011-05-05 BR BR112012028291A patent/BR112012028291A2/pt not_active IP Right Cessation
- 2011-05-05 EP EP11778348.0A patent/EP2566331B1/en active Active
- 2011-05-05 CN CN2011800333447A patent/CN102970871A/zh active Pending
- 2011-05-05 AU AU2011247995A patent/AU2011247995B2/en not_active Ceased
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- 2011-05-05 WO PCT/US2011/035363 patent/WO2011140343A1/en not_active Ceased
- 2011-05-05 EA EA201291168A patent/EA201291168A1/ru unknown
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2012
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2015
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Also Published As
| Publication number | Publication date |
|---|---|
| EP2566331A1 (en) | 2013-03-13 |
| US20120028918A1 (en) | 2012-02-02 |
| PH12012502159A1 (en) | 2013-02-04 |
| EP2566331B1 (en) | 2014-09-03 |
| SG185087A1 (en) | 2012-12-28 |
| US20110281901A1 (en) | 2011-11-17 |
| TW201206908A (en) | 2012-02-16 |
| KR20130071434A (ko) | 2013-06-28 |
| ZA201208265B (en) | 2013-07-31 |
| BR112012028291A2 (pt) | 2015-09-15 |
| PE20130217A1 (es) | 2013-03-21 |
| DOP2012000281A (es) | 2013-05-31 |
| US20150231265A1 (en) | 2015-08-20 |
| EP2566331A4 (en) | 2013-09-18 |
| HK1175947A1 (en) | 2013-07-19 |
| IL222751A0 (en) | 2012-12-31 |
| JP2013525501A (ja) | 2013-06-20 |
| MA34286B1 (fr) | 2013-06-01 |
| NZ603411A (en) | 2014-10-31 |
| AU2011247995B2 (en) | 2014-07-31 |
| CR20120556A (es) | 2013-02-20 |
| JP5835717B2 (ja) | 2015-12-24 |
| ES2519615T3 (es) | 2014-11-07 |
| CL2012003075A1 (es) | 2013-03-08 |
| UY33367A (es) | 2011-10-31 |
| AR081364A1 (es) | 2012-08-29 |
| WO2011140343A1 (en) | 2011-11-10 |
| CN102970871A (zh) | 2013-03-13 |
| EA201291168A1 (ru) | 2013-06-28 |
| AU2011247995A1 (en) | 2012-12-13 |
| CO6640262A2 (es) | 2013-03-22 |
| MX2012012837A (es) | 2013-01-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20170505 |