JP3737801B2 - プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウム、並びにそれを含む組成物 - Google Patents
プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウム、並びにそれを含む組成物 Download PDFInfo
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- JP3737801B2 JP3737801B2 JP2002533858A JP2002533858A JP3737801B2 JP 3737801 B2 JP3737801 B2 JP 3737801B2 JP 2002533858 A JP2002533858 A JP 2002533858A JP 2002533858 A JP2002533858 A JP 2002533858A JP 3737801 B2 JP3737801 B2 JP 3737801B2
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- Japan
- Prior art keywords
- pravastatin
- solution
- pravastatin sodium
- ammonium salt
- sodium
- 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.)
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- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 title claims description 116
- 229960001495 pravastatin sodium Drugs 0.000 title claims description 53
- 239000000203 mixture Substances 0.000 title claims description 22
- OQARDMYXSOFTLN-PZAWKZKUSA-N pravastatin lactone Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 OQARDMYXSOFTLN-PZAWKZKUSA-N 0.000 title claims description 6
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 91
- 229960002965 pravastatin Drugs 0.000 claims description 91
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 74
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 claims description 67
- 239000000243 solution Substances 0.000 claims description 62
- 238000000034 method Methods 0.000 claims description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 21
- 239000003960 organic solvent Substances 0.000 claims description 18
- 150000003863 ammonium salts Chemical class 0.000 claims description 16
- 238000002425 crystallisation Methods 0.000 claims description 15
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- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 claims description 8
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 claims description 8
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 7
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- 230000001376 precipitating effect Effects 0.000 claims 1
- -1 2-methyl-1-oxobutoxy Chemical group 0.000 description 40
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 239000013078 crystal Substances 0.000 description 21
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- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
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- 229910021529 ammonia Inorganic materials 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000013543 active substance Substances 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 239000001963 growth medium Substances 0.000 description 8
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- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 8
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- 150000003839 salts Chemical class 0.000 description 8
- VGMFHMLQOYWYHN-UHFFFAOYSA-N Compactin Natural products OCC1OC(OC2C(O)C(O)C(CO)OC2Oc3cc(O)c4C(=O)C(=COc4c3)c5ccc(O)c(O)c5)C(O)C(O)C1O VGMFHMLQOYWYHN-UHFFFAOYSA-N 0.000 description 7
- AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 description 7
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 7
- BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 6
- 239000006286 aqueous extract Substances 0.000 description 6
- 229920001429 chelating resin Polymers 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- VWBQYTRBTXKKOG-IYNICTALSA-M pravastatin sodium Chemical compound [Na+].C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC([O-])=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 VWBQYTRBTXKKOG-IYNICTALSA-M 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 230000033444 hydroxylation Effects 0.000 description 5
- 238000005805 hydroxylation reaction Methods 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000003729 cation exchange resin Substances 0.000 description 4
- 229940023913 cation exchange resins Drugs 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 235000010980 cellulose Nutrition 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 150000002596 lactones Chemical class 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000003125 aqueous solvent Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000010908 decantation Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 3
- WDAXFOBOLVPGLV-UHFFFAOYSA-N isobutyric acid ethyl ester Natural products CCOC(=O)C(C)C WDAXFOBOLVPGLV-UHFFFAOYSA-N 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- YKYONYBAUNKHLG-UHFFFAOYSA-N propyl acetate Chemical compound CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229910001415 sodium ion Inorganic materials 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 2
- 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 description 2
- 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 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 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
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- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 2
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- XUPYJHCZDLZNFP-UHFFFAOYSA-N butyl butanoate Chemical compound CCCCOC(=O)CCC XUPYJHCZDLZNFP-UHFFFAOYSA-N 0.000 description 2
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- 238000010790 dilution Methods 0.000 description 1
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- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
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- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
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- 239000012535 impurity Substances 0.000 description 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
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- 229920000058 polyacrylate Polymers 0.000 description 1
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- 229940068984 polyvinyl alcohol Drugs 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
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- 239000003755 preservative agent Substances 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical group O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- HUAZGNHGCJGYNP-UHFFFAOYSA-N propyl butyrate Chemical compound CCCOC(=O)CCC HUAZGNHGCJGYNP-UHFFFAOYSA-N 0.000 description 1
- MCSINKKTEDDPNK-UHFFFAOYSA-N propyl propionate Chemical compound CCCOC(=O)CC MCSINKKTEDDPNK-UHFFFAOYSA-N 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
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- RGFNRWTWDWVHDD-UHFFFAOYSA-N sec-butyl ester of butyric acid Natural products CCCC(=O)OCC(C)C RGFNRWTWDWVHDD-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 238000011172 small scale experimental method Methods 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940005573 sodium fumarate 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
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- 239000000600 sorbitol Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
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- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 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
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- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/04—Sodium compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
- C07D309/38—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms one oxygen atom in position 2 or 4, e.g. pyrones
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/225—Polycarboxylic acids
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/52—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Crystallography & Structural Chemistry (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23827800P | 2000-10-05 | 2000-10-05 | |
| PCT/US2001/031230 WO2002030415A1 (en) | 2000-10-05 | 2001-10-05 | Pravastatin sodium substantially free of pravastatin lactone and epi-pravastatin, and compositions containing same |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004278522A Division JP2005013238A (ja) | 2000-10-05 | 2004-09-24 | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
| JP2005237299A Division JP2006036781A (ja) | 2000-10-05 | 2005-08-18 | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2004510817A JP2004510817A (ja) | 2004-04-08 |
| JP2004510817A5 JP2004510817A5 (de) | 2005-10-20 |
| JP3737801B2 true JP3737801B2 (ja) | 2006-01-25 |
Family
ID=22897222
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002533858A Expired - Fee Related JP3737801B2 (ja) | 2000-10-05 | 2001-10-05 | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウム、並びにそれを含む組成物 |
| JP2004278522A Withdrawn JP2005013238A (ja) | 2000-10-05 | 2004-09-24 | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
| JP2005237299A Pending JP2006036781A (ja) | 2000-10-05 | 2005-08-18 | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
| JP2009191951A Withdrawn JP2009268479A (ja) | 2000-10-05 | 2009-08-21 | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
| JP2013011711A Withdrawn JP2013128486A (ja) | 2000-10-05 | 2013-01-25 | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
| JP2015152088A Pending JP2015212300A (ja) | 2000-10-05 | 2015-07-31 | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
Family Applications After (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004278522A Withdrawn JP2005013238A (ja) | 2000-10-05 | 2004-09-24 | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
| JP2005237299A Pending JP2006036781A (ja) | 2000-10-05 | 2005-08-18 | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
| JP2009191951A Withdrawn JP2009268479A (ja) | 2000-10-05 | 2009-08-21 | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
| JP2013011711A Withdrawn JP2013128486A (ja) | 2000-10-05 | 2013-01-25 | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
| JP2015152088A Pending JP2015212300A (ja) | 2000-10-05 | 2015-07-31 | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP1330245A4 (de) |
| JP (6) | JP3737801B2 (de) |
| KR (1) | KR20030059173A (de) |
| CN (1) | CN1468098A (de) |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006036781A (ja) * | 2000-10-05 | 2006-02-09 | Teva Gyogyszergyar Rt | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6444452B1 (en) * | 1999-11-30 | 2002-09-03 | Biogal Gyogyszergyar Rt. | Process for recovering statin compounds from a fermentation broth |
| EP1798214A3 (de) * | 1999-11-30 | 2007-08-01 | Teva Gyogyszergyár Zártköruen Muködo Részvenytarsaság | Verfahren zur Gewinnung von Statinverbindungen aus einer Fermentationsbrühe |
| EP1481674B1 (de) * | 1999-11-30 | 2008-01-02 | TEVA Gyógyszergyár Zártkörüen Müködö Részvénytársaság | Verfahren zur Rückgewinnung von Statinverbindungen aus einer Fermentationsbrühe |
| KR20020062340A (ko) | 1999-12-14 | 2002-07-25 | 비오갈 기오기스제르갸르 알티. | 신규 형태의 프라바스타틴 나트륨 |
| JP3236282B1 (ja) * | 2000-10-16 | 2001-12-10 | 三共株式会社 | プラバスタチンを精製する方法 |
| GB0218781D0 (en) | 2002-08-13 | 2002-09-18 | Astrazeneca Ab | Chemical process |
| EP1452519A1 (de) * | 2003-02-25 | 2004-09-01 | Balkanpharma-Razgrad AD | Verfahren zur Isolierung und Reinigung von Pravastatin-Natriumsalz |
| GB0312896D0 (en) | 2003-06-05 | 2003-07-09 | Astrazeneca Ab | Chemical process |
| 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 |
| JP2007512366A (ja) * | 2003-11-24 | 2007-05-17 | テバ ジョジセルジャール ザ−トケルエン ムケド レ−スベニュタ−ルシャシャ−グ | プラバスタチンの精製方法 |
| WO2006017698A2 (en) | 2004-08-06 | 2006-02-16 | Transform Pharmaceuticals, Inc. | Novel statin pharmaceutical compositions and related methods of treatment |
| ES2254028B1 (es) * | 2004-11-29 | 2007-03-01 | Ercros Industrial, S.A. | Procedimiento para la obtencion de pravastatina sodica purificada. |
| MX2007010431A (es) * | 2005-02-25 | 2007-10-11 | Teva Pharma | Proceso para purificar tadalafil. |
| JP4813841B2 (ja) * | 2005-07-25 | 2011-11-09 | キユーピー株式会社 | プラバスタチンナトリウムの製造方法 |
| HU229260B1 (en) * | 2010-11-29 | 2013-10-28 | Egis Gyogyszergyar Nyrt | Process for preparation of rosuvastatin salts |
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| JPS5221594B2 (de) * | 1973-09-29 | 1977-06-11 | ||
| CH624956A5 (de) * | 1975-02-07 | 1981-08-31 | Glaxo Operations Ltd | Verfahren zur entfernung von verunreinigungen aus clavulansaeure. |
| US4231938A (en) * | 1979-06-15 | 1980-11-04 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
| JPS572240A (en) * | 1980-06-06 | 1982-01-07 | Sankyo Co Ltd | Ml-236b derivative |
| DK149080C (da) * | 1980-06-06 | 1986-07-28 | Sankyo Co | Fremgangsmaade til fremstilling af derivater af ml-236b-carboxylsyre |
| JPS5889191A (ja) * | 1981-11-20 | 1983-05-27 | Sankyo Co Ltd | ３−ヒドロキシ−ｍｌ−２３６ｂ誘導体の製造法 |
| JPS5890509A (ja) * | 1981-11-25 | 1983-05-30 | Sankyo Co Ltd | 高コレステロ−ル血症治療用組成物 |
| JPH01190661A (ja) * | 1988-01-22 | 1989-07-31 | Konishi Kagaku Kogyo Kk | ４，４′−ジヒドロキシジフエニルスルホンの精製法 |
| JP2739328B2 (ja) * | 1988-09-14 | 1998-04-15 | 日本ケミファ株式会社 | ベンズイミダゾール化合物の精製方法 |
| US5202029A (en) * | 1991-03-13 | 1993-04-13 | Caron Kabushiki Kaisha | Process for purification of hmg-coa reductase inhibitors |
| NZ250609A (en) * | 1992-12-28 | 1995-07-26 | Sankyo Co | Hexahydronaphthalene esters and ring closed lactones; preparation and medicaments |
| JPH06256278A (ja) * | 1993-03-03 | 1994-09-13 | Nissan Chem Ind Ltd | 光学活性α−カルバモイルアルカン酸誘導体およびその製法 |
| CA2126365C (en) * | 1993-07-06 | 1999-08-24 | Steven W. Felman | Recovery of citric acid from impure process streams by addition of strong acids and salts thereof |
| ES2112042T3 (es) * | 1994-03-31 | 1998-03-16 | Cultor Oy | Procedimiento para la recuperacion de natamicina. |
| DK0784605T3 (da) * | 1995-08-03 | 2000-07-31 | Dsm Nv | Selektiv fremgangsmåde til deacyleringen af acylforbindelser |
| JPH09124655A (ja) * | 1995-11-01 | 1997-05-13 | Sankyo Co Ltd | 新規スクアレンシンターゼ阻害活性化合物 |
| EP0877089A1 (de) * | 1997-05-07 | 1998-11-11 | Gist-Brocades B.V. | Verfahren zur Herstellung eines Inhibitors der Hmg-Coa Reduktase |
| SI20072A (sl) * | 1998-09-18 | 2000-04-30 | LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. | Postopek za pridobivanje inhibitorjev HMG-CoA reduktaze |
| SI20070A (sl) * | 1998-09-18 | 2000-04-30 | LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. | Nove soli inhibitorjev HMG-CoA reduktaze |
| JP2000229855A (ja) * | 1998-12-07 | 2000-08-22 | Satoshi Takebe | プラバスタチンナトリウム錠 |
| CA2361701C (en) * | 1999-02-03 | 2007-04-10 | Institute For Drug Research Ltd. | Microbial process for preparing pravastatin |
| HUP9902352A1 (hu) * | 1999-07-12 | 2000-09-28 | Gyógyszerkutató Intézet Kft. | Eljárás pravasztatin mikrobiológiai előállítására |
| US6444452B1 (en) * | 1999-11-30 | 2002-09-03 | Biogal Gyogyszergyar Rt. | Process for recovering statin compounds from a fermentation broth |
| CA2422744A1 (en) * | 2000-10-05 | 2002-04-18 | Biogal Gyogyszergyar Rt. | Pravastatin sodium substantially free of pravastatin lactone and epi-pravastatin, and compositions containing same |
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2001
- 2001-10-05 CA CA002422744A patent/CA2422744A1/en not_active Abandoned
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- 2001-10-05 WO PCT/US2001/031230 patent/WO2002030415A1/en not_active Application Discontinuation
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- 2003-04-01 IS IS6766A patent/IS6766A/is unknown
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006036781A (ja) * | 2000-10-05 | 2006-02-09 | Teva Gyogyszergyar Rt | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
| JP2013128486A (ja) * | 2000-10-05 | 2013-07-04 | Teva Gyogyszergyar Zartkoruen Mukodo Rt | プラバスタチンラクトン及びエピプラバスタチンを実質的に含まないプラバスタチンナトリウムの製造方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CZ20031166A3 (cs) | 2004-04-14 |
| KR20030059173A (ko) | 2003-07-07 |
| JP2009268479A (ja) | 2009-11-19 |
| AU2002211462A1 (en) | 2002-04-22 |
| SK5232003A3 (en) | 2004-06-08 |
| HUP0400913A2 (en) | 2006-11-28 |
| JP2013128486A (ja) | 2013-07-04 |
| JP2005013238A (ja) | 2005-01-20 |
| CA2422744A1 (en) | 2002-04-18 |
| WO2002030415A9 (en) | 2002-10-31 |
| JP2006036781A (ja) | 2006-02-09 |
| CN1468098A (zh) | 2004-01-14 |
| EP1330245A4 (de) | 2004-10-20 |
| HRP20030347A2 (en) | 2005-04-30 |
| JP2004510817A (ja) | 2004-04-08 |
| NO20031532D0 (no) | 2003-04-04 |
| NO20031532L (no) | 2003-04-04 |
| ZA200302313B (en) | 2004-03-25 |
| PL361230A1 (en) | 2004-10-04 |
| IL155194A0 (en) | 2003-11-23 |
| MXPA03002963A (es) | 2005-01-25 |
| WO2002030415A1 (en) | 2002-04-18 |
| JP2015212300A (ja) | 2015-11-26 |
| NZ525631A (en) | 2005-05-27 |
| EP1330245A1 (de) | 2003-07-30 |
| IS6766A (is) | 2003-04-01 |
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