JP2003514798A - アトルバスタチンカルシウムの多形 - Google Patents
アトルバスタチンカルシウムの多形Info
- Publication number
- JP2003514798A JP2003514798A JP2001538875A JP2001538875A JP2003514798A JP 2003514798 A JP2003514798 A JP 2003514798A JP 2001538875 A JP2001538875 A JP 2001538875A JP 2001538875 A JP2001538875 A JP 2001538875A JP 2003514798 A JP2003514798 A JP 2003514798A
- Authority
- JP
- Japan
- Prior art keywords
- atorvastatin
- calcium
- salt
- hydrate
- atorvastatin calcium
- 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.)
- Withdrawn
Links
- OJRHUICOVVSGSY-RXMQYKEDSA-N (2s)-2-chloro-3-methylbutan-1-ol Chemical compound CC(C)[C@H](Cl)CO OJRHUICOVVSGSY-RXMQYKEDSA-N 0.000 title claims abstract description 59
- 229960001770 atorvastatin calcium Drugs 0.000 title claims abstract description 38
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- 159000000007 calcium salts Chemical class 0.000 claims description 29
- 239000012266 salt solution Substances 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 24
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 22
- 229960005370 atorvastatin Drugs 0.000 claims description 22
- 239000000243 solution Substances 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 17
- 239000007787 solid Substances 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical group [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 5
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims 3
- 239000002184 metal Substances 0.000 claims 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 claims 1
- 125000005210 alkyl ammonium group Chemical group 0.000 claims 1
- 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 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 11
- 229940079593 drug Drugs 0.000 abstract description 10
- 239000002552 dosage form Substances 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- -1 alkali metal salts Chemical class 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 108010007622 LDL Lipoproteins Proteins 0.000 description 6
- 102000007330 LDL Lipoproteins Human genes 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- VVRPOCPLIUDBSA-CNZCJKERSA-M sodium;(3r,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoate Chemical group [Na+].C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 VVRPOCPLIUDBSA-CNZCJKERSA-M 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 235000010980 cellulose Nutrition 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000001639 calcium acetate Substances 0.000 description 4
- 235000011092 calcium acetate Nutrition 0.000 description 4
- 229960005147 calcium acetate Drugs 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 230000000704 physical effect Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000008247 solid mixture Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 108010046315 IDL Lipoproteins Proteins 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000007942 carboxylates Chemical class 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 2
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 2
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 2
- 102000000853 LDL receptors Human genes 0.000 description 2
- 108010001831 LDL receptors Proteins 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000005599 alkyl carboxylate group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical class [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 229960000913 crospovidone Drugs 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 150000003871 sulfonates Chemical class 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- KJTLQQUUPVSXIM-ZCFIWIBFSA-M (R)-mevalonate Chemical compound OCC[C@](O)(C)CC([O-])=O KJTLQQUUPVSXIM-ZCFIWIBFSA-M 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
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UNMYWSMUMWPJLR-UHFFFAOYSA-L Calcium iodide Chemical compound [Ca+2].[I-].[I-] UNMYWSMUMWPJLR-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 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 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
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
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- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 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
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- 101000879758 Homo sapiens Sjoegren syndrome nuclear autoantigen 1 Proteins 0.000 description 1
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- FQCKMBLVYCEXJB-MNSAWQCASA-L atorvastatin calcium Chemical compound [Ca+2].C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 FQCKMBLVYCEXJB-MNSAWQCASA-L 0.000 description 1
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- 239000011692 calcium ascorbate Substances 0.000 description 1
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 description 1
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- 150000002596 lactones Chemical class 0.000 description 1
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- 229940002661 lipitor Drugs 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 1
- MZUOYVUQORIPHP-MNSAWQCASA-L magnesium;(3r,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoate Chemical group [Mg+2].C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 MZUOYVUQORIPHP-MNSAWQCASA-L 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
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- 230000010534 mechanism of action Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
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- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000019691 monocalcium phosphate Nutrition 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
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- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000005498 phthalate group Chemical class 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229940068984 polyvinyl alcohol Drugs 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
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- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
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- 230000004083 survival effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 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 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- VLCLHFYFMCKBRP-UHFFFAOYSA-N tricalcium;diborate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]B([O-])[O-].[O-]B([O-])[O-] VLCLHFYFMCKBRP-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16615399P | 1999-11-17 | 1999-11-17 | |
| US60/166,153 | 1999-11-17 | ||
| PCT/US2000/031555 WO2001036384A1 (en) | 1999-11-17 | 2000-11-16 | Polymorphic form of atorvastatin calcium |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009030514A Division JP2009102439A (ja) | 1999-11-17 | 2009-02-12 | アトルバスタチンカルシウムの多形 |
Publications (2)
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| JP2003514798A true JP2003514798A (ja) | 2003-04-22 |
| JP2003514798A5 JP2003514798A5 (enExample) | 2005-12-22 |
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| JP2001538875A Withdrawn JP2003514798A (ja) | 1999-11-17 | 2000-11-16 | アトルバスタチンカルシウムの多形 |
| JP2009030514A Pending JP2009102439A (ja) | 1999-11-17 | 2009-02-12 | アトルバスタチンカルシウムの多形 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009030514A Pending JP2009102439A (ja) | 1999-11-17 | 2009-02-12 | アトルバスタチンカルシウムの多形 |
Country Status (20)
| Country | Link |
|---|---|
| EP (3) | EP2206497A1 (enExample) |
| JP (2) | JP2003514798A (enExample) |
| KR (1) | KR20020063190A (enExample) |
| CN (1) | CN1423634A (enExample) |
| AT (2) | ATE288893T1 (enExample) |
| AU (1) | AU783002B2 (enExample) |
| CA (1) | CA2392096C (enExample) |
| CZ (1) | CZ20021642A3 (enExample) |
| DE (2) | DE60044884D1 (enExample) |
| ES (2) | ES2349364T3 (enExample) |
| HR (1) | HRP20020429B8 (enExample) |
| HU (1) | HUP0203257A3 (enExample) |
| IL (2) | IL149681A0 (enExample) |
| PL (1) | PL355805A1 (enExample) |
| PT (2) | PT1235799E (enExample) |
| SI (2) | SI1535613T1 (enExample) |
| SK (1) | SK286789B6 (enExample) |
| WO (1) | WO2001036384A1 (enExample) |
| YU (1) | YU35802A (enExample) |
| ZA (1) | ZA200203755B (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008530146A (ja) * | 2005-12-13 | 2008-08-07 | テバ ファーマシューティカル インダストリーズ リミティド | アトルバスタチン・ヘミカルシウムの結晶形及びその調製方法 |
| JP2012031130A (ja) * | 2010-07-28 | 2012-02-16 | Kyongbo Pharm Co Ltd | アトルバスタチンヘミカルシウム塩の新規な結晶形、その水和物、及びその製造方法 |
| JP2012046523A (ja) * | 2004-05-05 | 2012-03-08 | Pfizer Products Inc | アトルバスタチンの塩形態 |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7411075B1 (en) | 2000-11-16 | 2008-08-12 | Teva Pharmaceutical Industries Ltd. | Polymorphic form of atorvastatin calcium |
| PL362472A1 (en) * | 2000-11-03 | 2004-11-02 | Teva Pharma | Atorvastatin hemi-calcium form vii |
| IL156055A0 (en) | 2000-11-30 | 2003-12-23 | Teva Pharma | Novel crystal forms of atorvastatin hemi calcium and processes for their preparation as well as novel processes for preparing other forms |
| US7501450B2 (en) | 2000-11-30 | 2009-03-10 | Teva Pharaceutical Industries Ltd. | Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms |
| KR100790766B1 (ko) * | 2000-12-27 | 2008-01-03 | 테바 파마슈티컬 인더스트리즈 리미티드 | 아토르바스타틴의 결정 형태, 이의 제조방법 및 이를 포함하는 약제학적 조성물 |
| WO2002057229A1 (en) * | 2001-01-19 | 2002-07-25 | Biocon India Limited | FORM V CRYSTALLINE [R-(R*,R*)]-2-(4-FLUOROPHENYL)-ß,$G(D)-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1- HEPTANOIC ACID HEMI CALCIUM SALT. (ATORVASTATIN) |
| EP1423364B1 (en) * | 2001-06-29 | 2015-11-04 | Warner-Lambert Company LLC | Crystalline forms of [r-(r*,r*)]-2-(4-fluorophenyl)-beta, delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid calcium salt (2:1) (atorvastatin) |
| US7074818B2 (en) | 2001-07-30 | 2006-07-11 | Dr. Reddy's Laboratories Limited | Crystalline forms VI and VII of Atorvastatin calcium |
| JP2005500351A (ja) * | 2001-07-30 | 2005-01-06 | ドクター・レディーズ・ラボラトリーズ・リミテッド | 結晶形態ｖｉおよびｖｉｉのアトルバスタチンカルシウム |
| UA77990C2 (en) * | 2001-12-12 | 2007-02-15 | Crystalline calcium salt of (2:1) [r-(r*,r*)]-2-(4-fluorophenyl)-?,?-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrroleheptanic acid | |
| WO2003070702A1 (en) * | 2002-02-15 | 2003-08-28 | Teva Pharmaceutical Industries Ltd. | Novel crystal forms of atorvastatin hemi-calcium and processes for their preparation, as well as novel processes for preparing atorvastatin hemi-calcium forms i, viii and ix |
| IL163594A0 (en) | 2002-02-19 | 2005-12-18 | Teva Pharma | Processes for desolvating solvates of atorvastatinhemi-calcium and atorvastatin hemi-calcium essentially free of organic solvent |
| ATE409476T1 (de) * | 2002-06-13 | 2008-10-15 | Novartis Pharma Gmbh | Calciumsalze von statinen aus indol |
| GB0218781D0 (en) * | 2002-08-13 | 2002-09-18 | Astrazeneca Ab | Chemical process |
| CA2508871C (en) * | 2002-11-28 | 2008-09-09 | Teva Pharmaceutical Industries Ltd. | Crystalline form f of atorvastatin hemi-calcium salt |
| EP1424324A1 (en) * | 2002-11-28 | 2004-06-02 | Teva Pharmaceutical Industries Limited | Crystalline form F of Atorvastatin hemi-calcium salt |
| GB0312896D0 (en) | 2003-06-05 | 2003-07-09 | Astrazeneca Ab | Chemical process |
| US7790197B2 (en) | 2003-06-09 | 2010-09-07 | Warner-Lambert Company Llc | Pharmaceutical compositions of atorvastatin |
| US7655692B2 (en) | 2003-06-12 | 2010-02-02 | Pfizer Inc. | Process for forming amorphous atorvastatin |
| CA2465693A1 (en) * | 2003-06-12 | 2004-12-12 | Warner-Lambert Company Llc | Pharmaceutical compositions of atorvastatin |
| US20050271717A1 (en) | 2003-06-12 | 2005-12-08 | Alfred Berchielli | Pharmaceutical compositions of atorvastatin |
| UY28501A1 (es) | 2003-09-10 | 2005-04-29 | Astrazeneca Uk Ltd | Compuestos químicos |
| GB0324791D0 (en) | 2003-10-24 | 2003-11-26 | Astrazeneca Ab | Chemical process |
| MX2007000765A (es) * | 2004-07-20 | 2007-03-28 | Warner Lambert Co | Formas cristalinas de sal de calcio del acido (r-(r*, r*))-2- (4-fluorofenil)- beta,gama- dihidroxi-5- (1-metiletil)-3 -fenil-4-((fenilamino) (carbonil)-1ih -pirrol-1- heptanoico (2:1). |
| EP1694685A1 (en) | 2004-09-28 | 2006-08-30 | Teva Pharmaceutical Industries Ltd | Process for preparing forms of atorvastatin calcium substantially free of impurities |
| MX2007004425A (es) | 2004-10-18 | 2007-06-07 | Teva Pharma | Proceso para preparar hemi-calcio de atorvastatina amorfo disolviendo la sal en un solvente organico que es una mezcla de un alcohol y una cetona y/o un ester y removiendo el solvente. |
| KR20070067175A (ko) | 2004-10-28 | 2007-06-27 | 워너-램버트 캄파니 엘엘씨 | 무정형 아토르바스타틴 형성 방법 |
| WO2006048894A1 (en) * | 2004-11-05 | 2006-05-11 | Morepen Laboratories Limited | Novel crystalline forms of atorvastatin calcium and processes for preparing them. |
| CA2588216A1 (en) | 2004-11-22 | 2006-05-26 | Dexcel Pharma Technologies Ltd. | Stable atorvastatin formulations |
| CA2499047A1 (en) | 2005-03-01 | 2006-09-01 | Apotex Pharmachem Inc. | Process for producing atorvastatin hemicalcium |
| AU2006281229A1 (en) | 2005-08-15 | 2007-02-22 | Arrow International Limited | Crystalline and amorphous sodium atorvastatin |
| WO2007020421A1 (en) * | 2005-08-15 | 2007-02-22 | Arrow International Limited | Crystalline and amorphous sodium atorvastatin |
| CA2547216A1 (en) | 2005-09-21 | 2007-03-21 | Renuka D. Reddy | Process for annealing amorphous atorvastatin |
| EP1808162A1 (en) | 2005-11-21 | 2007-07-18 | Teva Pharmaceutical Industries Ltd. | Atorvastatin pharmaceutical formulation |
| EP1923057A1 (en) | 2005-11-21 | 2008-05-21 | Teva Pharmaceutical Industries Ltd | Atorvastatin pharmaceutical formulation |
| DE602006014193D1 (de) | 2005-11-21 | 2010-06-17 | Warner Lambert Co | Neue formen von är-(r*,r*)ü-2-(4-fluorphenyl)-b,d-dihydroxy-5-(1-methylethyl)-3-phenyl-4-ä(phenylamino)carbonylü-1h-pyrrol-1-heptansäure-magnesium |
| EP1810667A1 (en) | 2006-01-20 | 2007-07-25 | KRKA, tovarna zdravil, d.d., Novo mesto | Pharmaceutical composition comprising amorphous atorvastatin |
| US20090240064A1 (en) * | 2006-02-22 | 2009-09-24 | Venkata Panakala Rao Gogulapati | Crystalline form of atorvastatin hemi-calcium |
| KR101012917B1 (ko) * | 2007-03-02 | 2011-02-08 | 동아제약주식회사 | 피롤 헵탄산 화합물의 신규한 결정형 |
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| CZ201039A3 (cs) | 2010-01-19 | 2011-07-27 | Zentiva, K. S | Zpusob prumyslové výroby amorfní formy hemivápenaté soli (3R,5R) 7-[3-fenyl-4-fenylkarbamoyl-2-(4-fluorfenyl)-5-isopropylpyrrol-1-yl]-3,5-dihydroxyheptanové kyseliny (atorvastatinu) s vysokým specifickým povrchem a jeho použití v lékové forme |
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Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4681893A (en) * | 1986-05-30 | 1987-07-21 | Warner-Lambert Company | Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis |
| FI94339C (fi) * | 1989-07-21 | 1995-08-25 | Warner Lambert Co | Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi |
| SG45369A1 (en) * | 1993-01-19 | 1998-10-16 | Warner Lambert Co | Stable oral ci-981 formulation and process of preparing same |
| DE69634054T2 (de) * | 1995-07-17 | 2005-12-08 | Warner-Lambert Co. | Kristalline (R-(R*, R*))-2-(4-Fluorophenyl)-β, δ-Dihydroxy-5-(1-Methylethyl)-3-Phenyl-4-((Phenylamino)Carbonyl)-1H-Pyrrol-1-Heptancarbonsäure Hemi Calcium Salz (Atorvastatin) |
| HRP960313B1 (en) * | 1995-07-17 | 2002-08-31 | Warner Lambert Co | Form iii crystalline (r- (r*, r*)-2- (4-fluorophenyl) -beta-delta-hydroxy-5-(1-methylethyl) -3-phenyl-4- ((phenylamino) carbonyl -1h-pyrrole-1-heptanoic acid calcium salt (2:1) |
-
2000
- 2000-11-16 SI SI200031061T patent/SI1535613T1/sl unknown
- 2000-11-16 EP EP10157435A patent/EP2206497A1/en not_active Withdrawn
- 2000-11-16 YU YU35802A patent/YU35802A/sh unknown
- 2000-11-16 DE DE60044884T patent/DE60044884D1/de not_active Expired - Lifetime
- 2000-11-16 KR KR1020027006304A patent/KR20020063190A/ko not_active Ceased
- 2000-11-16 AT AT00978744T patent/ATE288893T1/de not_active IP Right Cessation
- 2000-11-16 AT AT04027375T patent/ATE478665T1/de not_active IP Right Cessation
- 2000-11-16 SI SI200030648T patent/SI1235799T1/xx unknown
- 2000-11-16 PL PL00355805A patent/PL355805A1/xx not_active Application Discontinuation
- 2000-11-16 JP JP2001538875A patent/JP2003514798A/ja not_active Withdrawn
- 2000-11-16 PT PT00978744T patent/PT1235799E/pt unknown
- 2000-11-16 EP EP04027375A patent/EP1535613B1/en not_active Expired - Lifetime
- 2000-11-16 ES ES04027375T patent/ES2349364T3/es not_active Expired - Lifetime
- 2000-11-16 HR HR20020429A patent/HRP20020429B8/xx not_active IP Right Cessation
- 2000-11-16 CZ CZ20021642A patent/CZ20021642A3/cs unknown
- 2000-11-16 EP EP00978744A patent/EP1235799B1/en not_active Expired - Lifetime
- 2000-11-16 CA CA002392096A patent/CA2392096C/en not_active Expired - Fee Related
- 2000-11-16 IL IL14968100A patent/IL149681A0/xx active IP Right Grant
- 2000-11-16 CN CN00818409A patent/CN1423634A/zh active Pending
- 2000-11-16 HU HU0203257A patent/HUP0203257A3/hu unknown
- 2000-11-16 SK SK674-2002A patent/SK286789B6/sk not_active IP Right Cessation
- 2000-11-16 PT PT04027375T patent/PT1535613E/pt unknown
- 2000-11-16 DE DE60018100T patent/DE60018100T2/de not_active Expired - Lifetime
- 2000-11-16 ES ES00978744T patent/ES2234699T3/es not_active Expired - Lifetime
- 2000-11-16 WO PCT/US2000/031555 patent/WO2001036384A1/en not_active Ceased
- 2000-11-16 AU AU16173/01A patent/AU783002B2/en not_active Ceased
-
2002
- 2002-05-10 ZA ZA200203755A patent/ZA200203755B/en unknown
- 2002-05-15 IL IL149681A patent/IL149681A/en unknown
-
2009
- 2009-02-12 JP JP2009030514A patent/JP2009102439A/ja active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012046523A (ja) * | 2004-05-05 | 2012-03-08 | Pfizer Products Inc | アトルバスタチンの塩形態 |
| JP2014028849A (ja) * | 2004-05-05 | 2014-02-13 | Pfizer Products Inc | アトルバスタチンの塩形態 |
| JP2008530146A (ja) * | 2005-12-13 | 2008-08-07 | テバ ファーマシューティカル インダストリーズ リミティド | アトルバスタチン・ヘミカルシウムの結晶形及びその調製方法 |
| JP2012031130A (ja) * | 2010-07-28 | 2012-02-16 | Kyongbo Pharm Co Ltd | アトルバスタチンヘミカルシウム塩の新規な結晶形、その水和物、及びその製造方法 |
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