JP2009504746A5 - - Google Patents

Info

Publication number

JP2009504746A5

JP2009504746A5 JP2008527053A JP2008527053A JP2009504746A5 JP 2009504746 A5 JP2009504746 A5 JP 2009504746A5 JP 2008527053 A JP2008527053 A JP 2008527053A JP 2008527053 A JP2008527053 A JP 2008527053A JP 2009504746 A5 JP2009504746 A5 JP 2009504746A5

Authority

JP

Japan

Prior art keywords

formulation

amount

range

acid

salt

Prior art date

2006-08-16

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.)

Withdrawn

Links

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• 238000009472 formulation Methods 0.000 claims 26
• 239000000203 mixture Substances 0.000 claims 26
• 150000003839 salts Chemical class 0.000 claims 13
• QNZCBYKSOIHPEH-UHFFFAOYSA-N Apixaban Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(CC2)C=3C=CC(=CC=3)N3C(CCCC3)=O)=C2C(C(N)=O)=N1 QNZCBYKSOIHPEH-UHFFFAOYSA-N 0.000 claims 10
• 229960003886 apixaban Drugs 0.000 claims 10
• 229920000858 Cyclodextrin Polymers 0.000 claims 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 9
• 239000001116 FEMA 4028 Substances 0.000 claims 8
• WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical class 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 8
• 235000011175 beta-cyclodextrine Nutrition 0.000 claims 8
• 229960004853 betadex Drugs 0.000 claims 8
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 8
• 229940123583 Factor Xa inhibitor Drugs 0.000 claims 7
• 125000000217 alkyl group Chemical group 0.000 claims 5
• 239000007972 injectable composition Substances 0.000 claims 4
• OFJRNBWSFXEHSA-UHFFFAOYSA-N 2-(3-amino-1,2-benzoxazol-5-yl)-n-[4-[2-[(dimethylamino)methyl]imidazol-1-yl]-2-fluorophenyl]-5-(trifluoromethyl)pyrazole-3-carboxamide Chemical group CN(C)CC1=NC=CN1C(C=C1F)=CC=C1NC(=O)C1=CC(C(F)(F)F)=NN1C1=CC=C(ON=C2N)C2=C1 OFJRNBWSFXEHSA-UHFFFAOYSA-N 0.000 claims 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
• 239000007853 buffer solution Substances 0.000 claims 3
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims 3
• 229950010535 razaxaban Drugs 0.000 claims 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 2
• 229910052783 alkali metal Inorganic materials 0.000 claims 2
• -1 alkali metal citrate Chemical class 0.000 claims 2
• 239000002585 base Substances 0.000 claims 2
• 239000000872 buffer Substances 0.000 claims 2
• 229910052736 halogen Inorganic materials 0.000 claims 2
• 238000002347 injection Methods 0.000 claims 2
• 239000007924 injection Substances 0.000 claims 2
• 239000008194 pharmaceutical composition Substances 0.000 claims 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
• 239000001509 sodium citrate Substances 0.000 claims 2
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims 2
• BBMHARZCALWXSL-UHFFFAOYSA-M sodium dihydrogenphosphate monohydrate Chemical compound O.[Na+].OP(O)([O-])=O BBMHARZCALWXSL-UHFFFAOYSA-M 0.000 claims 2
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 claims 1
• 208000004476 Acute Coronary Syndrome Diseases 0.000 claims 1
• 206010051055 Deep vein thrombosis Diseases 0.000 claims 1
• 206010014522 Embolism venous Diseases 0.000 claims 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims 1
• 239000007983 Tris buffer Substances 0.000 claims 1
• 206010047249 Venous thrombosis Diseases 0.000 claims 1
• 239000003513 alkali Substances 0.000 claims 1
• 150000001340 alkali metals Chemical class 0.000 claims 1
• 125000003545 alkoxy group Chemical group 0.000 claims 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims 1
• 239000013011 aqueous formulation Substances 0.000 claims 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims 1
• 229940092714 benzenesulfonic acid Drugs 0.000 claims 1
• 239000001177 diphosphate Substances 0.000 claims 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims 1
• 235000011180 diphosphates Nutrition 0.000 claims 1
• 229940079593 drug Drugs 0.000 claims 1
• 239000003814 drug Substances 0.000 claims 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims 1
• 125000005843 halogen group Chemical group 0.000 claims 1
• 150000002367 halogens Chemical class 0.000 claims 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
• 230000007794 irritation Effects 0.000 claims 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
• 239000011976 maleic acid Substances 0.000 claims 1
• 239000001630 malic acid Substances 0.000 claims 1
• 235000011090 malic acid Nutrition 0.000 claims 1
• 229910000000 metal hydroxide Inorganic materials 0.000 claims 1
• 150000004692 metal hydroxides Chemical class 0.000 claims 1
• PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 claims 1
• 239000008363 phosphate buffer Substances 0.000 claims 1
• 125000006684 polyhaloalkyl group Polymers 0.000 claims 1
• 229940097346 sulfobutylether-beta-cyclodextrin Drugs 0.000 claims 1
• 239000011975 tartaric acid Substances 0.000 claims 1
• 235000002906 tartaric acid Nutrition 0.000 claims 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 1
• 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 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims 1
• 208000004043 venous thromboembolism Diseases 0.000 claims 1
• 0 *c1n[n](Cc(cc2)cc3c2c(N)n[o]3)c(C(Nc(cc2)c(*)cc2-[n]2c(CN(*)*)ncc2)=O)c1 Chemical compound *c1n[n](Cc(cc2)cc3c2c(N)n[o]3)c(C(Nc(cc2)c(*)cc2-[n]2c(CN(*)*)ncc2)=O)c1 0.000 description 1