UA73829C2 - A method for the preparation of non-crystalline atorvastatin calcium and pharmaceutical composition - Google Patents
A method for the preparation of non-crystalline atorvastatin calcium and pharmaceutical composition Download PDFInfo
- Publication number
- UA73829C2 UA73829C2 UA2003076436A UA2003076436A UA73829C2 UA 73829 C2 UA73829 C2 UA 73829C2 UA 2003076436 A UA2003076436 A UA 2003076436A UA 2003076436 A UA2003076436 A UA 2003076436A UA 73829 C2 UA73829 C2 UA 73829C2
- Authority
- UA
- Ukraine
- Prior art keywords
- atorvastatin
- solution
- calcium
- volume
- stage
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 45
- 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 42
- 229960001770 atorvastatin calcium Drugs 0.000 title claims abstract description 42
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title description 12
- 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 abstract description 39
- 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 abstract description 39
- 229960005370 atorvastatin Drugs 0.000 claims abstract description 39
- 159000000007 calcium salts Chemical class 0.000 claims abstract description 20
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 14
- 239000000243 solution Substances 0.000 claims description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
- 150000001875 compounds Chemical class 0.000 claims description 27
- 239000002904 solvent Substances 0.000 claims description 24
- 239000002244 precipitate Substances 0.000 claims description 18
- 150000002596 lactones Chemical class 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- -1 tert-amyl Chemical group 0.000 claims description 15
- 239000008346 aqueous phase Substances 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 238000010511 deprotection reaction Methods 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 6
- MMCOUVMKNAHQOY-UHFFFAOYSA-N carbonoperoxoic acid Chemical group OOC(O)=O MMCOUVMKNAHQOY-UHFFFAOYSA-N 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 238000006386 neutralization reaction Methods 0.000 claims description 5
- 239000012071 phase Substances 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 238000007142 ring opening reaction Methods 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- BWFCZHDTTAYGNN-CNZCJKERSA-N calcium;(3r,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound [Ca].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 BWFCZHDTTAYGNN-CNZCJKERSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 230000009466 transformation Effects 0.000 claims description 3
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 230000008030 elimination Effects 0.000 claims description 2
- 238000003379 elimination reaction Methods 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 238000001556 precipitation Methods 0.000 claims 4
- 230000008021 deposition Effects 0.000 claims 2
- 238000001035 drying Methods 0.000 claims 2
- 238000001914 filtration Methods 0.000 claims 2
- 238000005406 washing Methods 0.000 claims 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 13
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 239000000843 powder Substances 0.000 abstract description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 abstract description 3
- 239000011575 calcium Substances 0.000 abstract description 3
- 239000002775 capsule Substances 0.000 abstract description 3
- 239000008101 lactose Substances 0.000 abstract description 3
- 239000003826 tablet Substances 0.000 abstract description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract description 2
- 229910052791 calcium Inorganic materials 0.000 abstract description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 abstract 1
- 239000003529 anticholesteremic agent Substances 0.000 abstract 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract 1
- 150000001735 carboxylic acids Chemical group 0.000 abstract 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- 238000004809 thin layer chromatography Methods 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 150000003839 salts Chemical group 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 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 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 125000002843 carboxylic acid group Chemical group 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 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 2
- 229920002307 Dextran Polymers 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 239000005913 Maltodextrin Substances 0.000 description 2
- 229920002774 Maltodextrin Polymers 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 239000004368 Modified starch Substances 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229940035034 maltodextrin Drugs 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 235000019426 modified starch Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000003495 polar organic solvent Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- OUCSEDFVYPBLLF-KAYWLYCHSA-N 5-(4-fluorophenyl)-1-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-n,4-diphenyl-2-propan-2-ylpyrrole-3-carboxamide Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@H]2OC(=O)C[C@H](O)C2)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 OUCSEDFVYPBLLF-KAYWLYCHSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- UNMYWSMUMWPJLR-UHFFFAOYSA-L Calcium iodide Chemical compound [Ca+2].[I-].[I-] UNMYWSMUMWPJLR-UHFFFAOYSA-L 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical group CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 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
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- YMGDMIIYRIYUFO-UHFFFAOYSA-J [Ca+2].[Ca+2].[I-].[I-].[I-].[I-] Chemical compound [Ca+2].[Ca+2].[I-].[I-].[I-].[I-] YMGDMIIYRIYUFO-UHFFFAOYSA-J 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
- 239000001639 calcium acetate Substances 0.000 description 1
- 235000011092 calcium acetate Nutrition 0.000 description 1
- 229960005147 calcium acetate Drugs 0.000 description 1
- 229940061587 calcium behenate Drugs 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 229940046413 calcium iodide Drugs 0.000 description 1
- 229910001640 calcium iodide Inorganic materials 0.000 description 1
- QXDMQSPYEZFLGF-UHFFFAOYSA-L calcium oxalate Chemical compound [Ca+2].[O-]C(=O)C([O-])=O QXDMQSPYEZFLGF-UHFFFAOYSA-L 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- SMBKCSPGKDEPFO-UHFFFAOYSA-L calcium;docosanoate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCCCCCC([O-])=O SMBKCSPGKDEPFO-UHFFFAOYSA-L 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000002563 ionic surfactant Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 150000007518 monoprotic acids Chemical class 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- ONQDVAFWWYYXHM-UHFFFAOYSA-M potassium lauryl sulfate Chemical compound [K+].CCCCCCCCCCCCOS([O-])(=O)=O ONQDVAFWWYYXHM-UHFFFAOYSA-M 0.000 description 1
- 229940116985 potassium lauryl sulfate Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Obesity (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SI200100010A SI20814A (sl) | 2001-01-23 | 2001-01-23 | Priprava amorfnega atorvastatina |
| PCT/IB2002/000161 WO2002059087A1 (en) | 2001-01-23 | 2002-01-22 | Preparation of non-crystalline atorvastatin calcium |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA73829C2 true UA73829C2 (en) | 2005-09-15 |
Family
ID=20432812
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA2003076436A UA73829C2 (en) | 2001-01-23 | 2002-01-22 | A method for the preparation of non-crystalline atorvastatin calcium and pharmaceutical composition |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US6750353B2 (https=) |
| EP (1) | EP1373202B1 (https=) |
| JP (1) | JP4336106B2 (https=) |
| KR (1) | KR100882066B1 (https=) |
| CN (1) | CN1260213C (https=) |
| AT (1) | ATE294159T1 (https=) |
| AU (1) | AU2002219455B2 (https=) |
| BG (1) | BG108017A (https=) |
| BR (1) | BR0206637A (https=) |
| CA (1) | CA2435954C (https=) |
| CZ (1) | CZ20031988A3 (https=) |
| DE (1) | DE60203894T2 (https=) |
| DK (1) | DK1373202T3 (https=) |
| EE (1) | EE05270B1 (https=) |
| ES (1) | ES2240748T3 (https=) |
| HR (1) | HRP20030575B1 (https=) |
| HU (1) | HU227535B1 (https=) |
| IL (2) | IL157068A0 (https=) |
| MX (1) | MXPA03006548A (https=) |
| PL (1) | PL209428B1 (https=) |
| RS (1) | RS51010B (https=) |
| RU (1) | RU2324679C2 (https=) |
| SI (2) | SI20814A (https=) |
| SK (1) | SK286593B6 (https=) |
| UA (1) | UA73829C2 (https=) |
| WO (1) | WO2002059087A1 (https=) |
| ZA (1) | ZA200305307B (https=) |
Families Citing this family (46)
| 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 |
| 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 |
| CA2622477A1 (en) | 2000-12-27 | 2002-07-04 | Teva Pharmaceutical Industries Ltd. | Crystalline forms of atorvastatin |
| WO2002068335A2 (en) * | 2001-02-27 | 2002-09-06 | Council Of Scientific And Industrial Research | Essential oil composition for potable water disinfection |
| SK16002003A3 (sk) | 2001-06-29 | 2004-12-01 | Warner-Lambert Company Llc | Kryštalické formy vápenatej soli (2:1) [R-(R*,R*)]-2-(4-fluóro- fenyl)-beta,delta-dihydroxy-5-(1-metyletyl)-3-fenyl-4- [(fenylamino)karbonyl]-1H-pyrrol-1-heptánovej kyseliny (atorvastatín) |
| WO2005033078A1 (en) * | 2003-10-07 | 2005-04-14 | Biocon Limited | Process for the production of atorvastatin calcium |
| HU227124B1 (en) * | 2001-09-14 | 2010-07-28 | Egis Gyogyszergyar Nyilvanosan | Polymorphs of 1-pyrrole derivative, intermediate for the preparation of atorvastatin |
| CN100379723C (zh) | 2002-02-19 | 2008-04-09 | 特瓦制药工业有限公司 | 阿托伐他汀半钙脱溶剂的方法和基本上不含有机溶剂的阿托伐他汀半钙 |
| ITMI20020907A1 (it) * | 2002-04-29 | 2003-10-29 | Chemi Spa | Processo di preparazione della forma amorfa del sale di calcio della atorvastatina |
| CA2385529A1 (en) * | 2002-05-21 | 2003-11-21 | Bernard Charles Sherman | Stable dosage forms comprising atorvastatin calcium |
| CA2520740C (en) * | 2003-04-11 | 2012-06-05 | Lek Pharmaceuticals D.D. | Process for the preparation of amorphous calcium salt of atorvastatin |
| US7790197B2 (en) | 2003-06-09 | 2010-09-07 | Warner-Lambert Company Llc | Pharmaceutical compositions of atorvastatin |
| US20050271717A1 (en) | 2003-06-12 | 2005-12-08 | Alfred Berchielli | Pharmaceutical compositions of atorvastatin |
| US7655692B2 (en) | 2003-06-12 | 2010-02-02 | Pfizer Inc. | Process for forming amorphous atorvastatin |
| EP1648903A2 (en) | 2003-07-02 | 2006-04-26 | Egis Gyogyszergyar Rt. | Process for the preparation of amorphous form of a platelet aggregation inhibitor drug |
| AU2003247327A1 (en) * | 2003-07-15 | 2005-01-28 | Eos Eczacibasi Ozgun Kimyasal Urunler Sanyi Ve Ticaret A.S. | Process for the preparation of amortphous atorvastatin calcium without interconversion of any crystalline form |
| JP2007517028A (ja) * | 2003-12-29 | 2007-06-28 | レツク・フアーマシユーテイカルズ・デー・デー | 非晶質の（４ｒ−シス）−６−［２−［３−フェニル−４−（フェニルカルバモイル）−２−（４−フルオロフェニル）−５−（１−メチルエチル）−ピロール−１−イル］−エチル］−２，２−ジメチル−［１，３］−ジオキサン−４−イル−酢酸を調製する方法 |
| ATE545629T1 (de) | 2004-03-17 | 2012-03-15 | Ranbaxy Lab Ltd | Verfahren zur herstellung von atorvastatin- calcium in amorpher form |
| US7875731B2 (en) | 2004-05-05 | 2011-01-25 | Pfizer Inc. | Salt forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β, δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)Carbonyl]-1H-pyrrole-1-heptanoic acid |
| US8044086B2 (en) * | 2004-07-16 | 2011-10-25 | Lek Pharmaceuticals D.D. | Oxidative degradation products of atorvastatin calcium |
| CA2701710C (en) | 2004-07-20 | 2013-08-27 | Warner-Lambert Company Llc | Novel 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) |
| WO2006011155A1 (en) * | 2004-07-26 | 2006-02-02 | Apollo International Limited | One pot process for amorphous atorvastain calcium |
| US7645888B2 (en) | 2004-08-27 | 2010-01-12 | Biocon Limited | Process for the production of amorphous atorvastatin calcium |
| AU2005298383A1 (en) | 2004-10-28 | 2006-05-04 | Warner-Lambert Company Llc | Process for forming amorphous atorvastatin |
| ES2270722B1 (es) * | 2005-09-15 | 2008-03-01 | Ercros Industrial, S.A. | Procedimiento para la obtencion de atorvastatina calcica amorfa. |
| US20090216029A1 (en) * | 2005-09-16 | 2009-08-27 | Yatendra Kumar | Process for the production of atorvastatin calcium in amorphous form |
| CA2547216A1 (en) | 2005-09-21 | 2007-03-21 | Renuka D. Reddy | Process for annealing amorphous atorvastatin |
| ATE466840T1 (de) | 2005-11-21 | 2010-05-15 | Warner Lambert Co | Neue formen von är-(r*,r*)ü-2-(4-fluorphenyl)-b,d-dihydroxy-5-( -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 |
| EP1979313A1 (en) * | 2006-01-31 | 2008-10-15 | Jubilant Organosys Limited | Process for the preparation of amorphous atorvastatin calcium salt |
| CN100406438C (zh) * | 2006-06-30 | 2008-07-30 | 浙江新东港药业股份有限公司 | 一种无定型阿伐他汀钙的制备方法 |
| US20100113802A1 (en) * | 2006-11-02 | 2010-05-06 | Cadila Pharmaceuticals Limited | Process for preparing amorphous atorvastatin hemi calcium salt and its itermediate |
| KR100833439B1 (ko) * | 2007-01-02 | 2008-05-29 | 씨제이제일제당 (주) | 비결정형 아토르바스타틴 칼슘의 개선된 제조방법 |
| WO2009052246A1 (en) | 2007-10-17 | 2009-04-23 | Ovokaitys, Todd, F. | Process for the modification of the solid state of a compound and co-amorphous compositions produced with same |
| WO2009139730A1 (en) * | 2008-05-13 | 2009-11-19 | Ulkar Kimya San. Ve Tic. A.S. | Preparation of novel non-crystalline forms of atorvastatin calcium |
| KR101050722B1 (ko) | 2008-12-02 | 2011-07-21 | 대웅바이오 주식회사 | 무정형 아토르바스타틴 칼슘염의 제조방법 |
| US8115015B2 (en) * | 2009-01-26 | 2012-02-14 | Cadila Healthcare Limited | Process for the preparation of amorphous atorvastatin calcium |
| US20130041162A1 (en) * | 2010-04-19 | 2013-02-14 | Dsm Sinochem Pharmaceuticals Netherlands B.V. | Production of atorvastatin low in ether impurities |
| HUP1000299A2 (hu) | 2010-06-08 | 2012-02-28 | Nanoform Cardiovascular Therapeutics Ltd | Nanostrukturált Atorvastatint, gyógyszerészetileg elfogadott sóit és kokristályait tartalmazó készítmény és eljárás elõállításukra |
| CN102796036B (zh) * | 2012-09-12 | 2014-06-04 | 江苏阿尔法药业有限公司 | 一种阿托伐他汀钙的制备方法 |
| US10202598B2 (en) | 2014-05-30 | 2019-02-12 | Todd Frank Ovokaitys | Methods and systems for generation, use, and delivery of activated stem cells |
| US10384985B2 (en) | 2014-06-06 | 2019-08-20 | B.K. Consultants, Inc. | Methods and compositions for increasing the yield of, and beneficial chemical composition of, certain plants |
| US10040728B2 (en) | 2014-06-06 | 2018-08-07 | Todd Frank Ovokaitys | Methods and compositions for increasing the bioactivity of nutrients |
| CN113321607A (zh) * | 2020-02-28 | 2021-08-31 | 北京福元医药股份有限公司沧州分公司 | 一种阿托伐他汀钙中间体的纯化方法 |
| WO2022126109A1 (en) | 2020-12-08 | 2022-06-16 | Ovokaitys Todd Frank | Methods and systems for increased production of stem cells |
Family Cites Families (17)
| 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 |
| US5216174A (en) | 1988-02-22 | 1993-06-01 | Warner-Lambert Co. | Process for trans-6-[12-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| US5245047A (en) | 1988-02-22 | 1993-09-14 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| US5003080A (en) | 1988-02-22 | 1991-03-26 | Warner-Lambert Company | Process for trans-6-(2-(substituted-pyrrol-1-yl)alkyl)pryan-2-one inhibitors of cholesterol synthesis |
| US5149837A (en) | 1988-02-22 | 1992-09-22 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| US5097045A (en) | 1989-02-01 | 1992-03-17 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| US5124482A (en) | 1988-02-22 | 1992-06-23 | Warner-Lambert Company | Process for trans-6-(2-substituted-pyrrol-1-yl)alkyl)pyran-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 |
| US5103024A (en) | 1990-10-17 | 1992-04-07 | Warner-Lambert Company | Process for the synthesis of (4r-cis)-1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate |
| US5155251A (en) | 1991-10-11 | 1992-10-13 | Warner-Lambert Company | Process for the synthesis of (5R)-1,1-dimethylethyl-6-cyano-5-hydroxy-3-oxo-hexanoate |
| US5298627A (en) | 1993-03-03 | 1994-03-29 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
| US5798375A (en) * | 1995-07-03 | 1998-08-25 | Sankyo Company, Limited | Treatment of arteriosclerosis and xanthoma |
| HRP960312B1 (en) * | 1995-07-17 | 2001-10-31 | Warner Lambert Co | NOVEL PROCESS FOR THE PRODUCTION OF AMORPHOUS /R-(R*, R*)/-2-(4-FLUOROPHENYL)-"beta", "delta"-DIHYDROXY-5-PHENYL-4-/(PHENYLAMINO)CARBONYL/-1H-PYRROLE -1-HEPTANOIC ACID CALCIUM SALT (2 : 1) |
| 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) |
| KR100389518B1 (ko) * | 1995-07-17 | 2003-11-15 | 워너-램버트 캄파니 엘엘씨 | 결정질[r-(r*,r*)]-2-(4-플루오로페닐)-베타,델타-디히드록시-5-(1-메틸에틸)-3-페닐-4-[(페닐아미노)카르보닐]-1h-피롤-1-헵탄산헤미칼슘염(아토르바스타틴) |
| US6087511A (en) * | 1996-07-16 | 2000-07-11 | Warner-Lambert Company | Process for the production of amorphous [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl )-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid) calcium salt (2:1) |
| IN191236B (https=) * | 1999-05-25 | 2003-10-11 | Ranbaxy Lab Ltd |
-
2001
- 2001-01-23 SI SI200100010A patent/SI20814A/sl not_active IP Right Cessation
-
2002
- 2002-01-22 JP JP2002559389A patent/JP4336106B2/ja not_active Expired - Fee Related
- 2002-01-22 WO PCT/IB2002/000161 patent/WO2002059087A1/en not_active Ceased
- 2002-01-22 CN CNB028039688A patent/CN1260213C/zh not_active Expired - Fee Related
- 2002-01-22 UA UA2003076436A patent/UA73829C2/uk unknown
- 2002-01-22 RU RU2003124962/04A patent/RU2324679C2/ru not_active IP Right Cessation
- 2002-01-22 EE EEP200300333A patent/EE05270B1/xx not_active IP Right Cessation
- 2002-01-22 MX MXPA03006548A patent/MXPA03006548A/es active IP Right Grant
- 2002-01-22 CZ CZ20031988A patent/CZ20031988A3/cs unknown
- 2002-01-22 DE DE60203894T patent/DE60203894T2/de not_active Expired - Lifetime
- 2002-01-22 AU AU2002219455A patent/AU2002219455B2/en not_active Ceased
- 2002-01-22 SI SI200230156T patent/SI1373202T1/sl unknown
- 2002-01-22 HU HU0302797A patent/HU227535B1/hu not_active IP Right Cessation
- 2002-01-22 HR HR20030575A patent/HRP20030575B1/xx not_active IP Right Cessation
- 2002-01-22 DK DK02734878T patent/DK1373202T3/da active
- 2002-01-22 CA CA002435954A patent/CA2435954C/en not_active Expired - Fee Related
- 2002-01-22 EP EP02734878A patent/EP1373202B1/en not_active Expired - Lifetime
- 2002-01-22 AT AT02734878T patent/ATE294159T1/de active
- 2002-01-22 ES ES02734878T patent/ES2240748T3/es not_active Expired - Lifetime
- 2002-01-22 SK SK908-2003A patent/SK286593B6/sk not_active IP Right Cessation
- 2002-01-22 IL IL15706802A patent/IL157068A0/xx unknown
- 2002-01-22 KR KR1020037009509A patent/KR100882066B1/ko not_active Expired - Fee Related
- 2002-01-22 RS YUP-568/03A patent/RS51010B/sr unknown
- 2002-01-22 BR BR0206637-8A patent/BR0206637A/pt not_active IP Right Cessation
- 2002-01-22 PL PL361763A patent/PL209428B1/pl unknown
- 2002-12-18 US US10/323,444 patent/US6750353B2/en not_active Expired - Fee Related
-
2003
- 2003-07-09 ZA ZA200305307A patent/ZA200305307B/xx unknown
- 2003-07-22 BG BG108017A patent/BG108017A/bg unknown
- 2003-07-23 IL IL157068A patent/IL157068A/en not_active IP Right Cessation
- 2003-10-03 US US10/677,344 patent/US7074940B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| UA73829C2 (en) | A method for the preparation of non-crystalline atorvastatin calcium and pharmaceutical composition | |
| RS56803B1 (sr) | Postupak za proizvodnju 2-[4-(3-ili2-fluorobenziloksi)benzilamino] propanamida sa visokim stepenom čistoće | |
| AU2002219455A1 (en) | Preparation of non-crystalline atorvastatin calcium | |
| EP1345896B1 (en) | Crystalline forms of atorvastatin | |
| JP4234429B2 (ja) | 水酸化カルシウムによる〔Ｒ（Ｒ＊，Ｒ＊）〕−２−（４−フルオロフェニル）−β，δ−ジヒドロキシ−５−（１−メチルエチル）−３−フェニル−４−〔（フェニルアミノ）カルボニル〕−１Ｈ−ピロール−１−ヘプタン酸エステルの加水分解 | |
| AU2002232891A1 (en) | Hydrolysis of [R(R*,R*)]-2-(4-fluorophenyl)-beta,delta -dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino) carbonyl]-1H-pyrrole-1-heptanoic acid esters with calcium hydroxide | |
| HUP0203257A2 (hu) | Atorvastatin kalcium polimorf módosulatai, eljárás az előállításukra és ezeket tartalmazó gyógyszerkészítmények | |
| HUP0402590A2 (hu) | (3R,5R)7-[3-fenil-4-fenilkarbamoil-2-(4-fluorfenil)-5-izopropil-pirrol-1-il]-3,5-dihidroxi-heptánsav (Atorvastatin) amorf hemikálcium-sójának előállítási módszere | |
| US20080269315A1 (en) | Crystalline form | |
| KR100829268B1 (ko) | 비정질 아토바스타틴 칼슘의 제조 방법 | |
| US20050165242A1 (en) | Process for the preparation of amorphous atorvastatin calcium |