ZA200302313B - Pravastatin sodium substantially free of pravastatin lactone and epi-pravastatin, and compositions containing same. - Google Patents
Pravastatin sodium substantially free of pravastatin lactone and epi-pravastatin, and compositions containing same. Download PDFInfo
- Publication number
- ZA200302313B ZA200302313B ZA200302313A ZA200302313A ZA200302313B ZA 200302313 B ZA200302313 B ZA 200302313B ZA 200302313 A ZA200302313 A ZA 200302313A ZA 200302313 A ZA200302313 A ZA 200302313A ZA 200302313 B ZA200302313 B ZA 200302313B
- Authority
- ZA
- South Africa
- Prior art keywords
- pravastatin
- sodium
- salt
- acid
- impurities
- Prior art date
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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 198
- 229960002965 pravastatin Drugs 0.000 title claims description 116
- 229960001495 pravastatin sodium Drugs 0.000 title claims description 74
- 239000000203 mixture Substances 0.000 title claims description 27
- 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 15
- 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 114
- 239000000243 solution Substances 0.000 claims description 55
- 238000000034 method Methods 0.000 claims description 49
- GJRQTCIYDGXPES-UHFFFAOYSA-N isobutyl acetate Chemical compound CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 claims description 38
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- -1 alkali metal cation Chemical class 0.000 claims description 24
- 238000000855 fermentation Methods 0.000 claims description 24
- 230000004151 fermentation Effects 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- 238000000605 extraction Methods 0.000 claims description 23
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 22
- 239000003960 organic solvent Substances 0.000 claims description 22
- 239000007787 solid Substances 0.000 claims description 22
- 239000012535 impurity Substances 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 238000002955 isolation Methods 0.000 claims description 16
- 238000000746 purification Methods 0.000 claims description 16
- 150000001412 amines Chemical class 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 14
- 159000000000 sodium salts Chemical class 0.000 claims description 12
- 239000013078 crystal Substances 0.000 claims description 11
- 238000002425 crystallisation Methods 0.000 claims description 11
- 230000008025 crystallization Effects 0.000 claims description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 10
- 229910052783 alkali metal Inorganic materials 0.000 claims description 10
- 150000003863 ammonium salts Chemical class 0.000 claims description 10
- 239000002585 base Substances 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 239000011734 sodium Substances 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 239000003456 ion exchange resin Substances 0.000 claims description 8
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 8
- 229910052708 sodium Inorganic materials 0.000 claims description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 7
- 150000001768 cations Chemical class 0.000 claims description 7
- 238000000354 decomposition reaction Methods 0.000 claims description 7
- 238000001953 recrystallisation Methods 0.000 claims description 7
- 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 6
- 239000012296 anti-solvent Substances 0.000 claims description 6
- 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 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 238000005185 salting out Methods 0.000 claims description 5
- 238000004108 freeze drying Methods 0.000 claims description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- 235000019270 ammonium chloride Nutrition 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- 150000001735 carboxylic acids Chemical class 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims description 2
- 150000003141 primary amines Chemical class 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 claims 4
- 239000002552 dosage form Substances 0.000 claims 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 230000002378 acidificating effect Effects 0.000 claims 1
- 125000005210 alkyl ammonium group Chemical group 0.000 claims 1
- 125000005907 alkyl ester group Chemical group 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 150000007529 inorganic bases Chemical class 0.000 claims 1
- 244000005700 microbiome Species 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 22
- 235000010633 broth Nutrition 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000011347 resin Substances 0.000 description 13
- 229920005989 resin Polymers 0.000 description 13
- 229910021529 ammonia Inorganic materials 0.000 description 10
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 8
- 238000001914 filtration Methods 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 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 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 229920001429 chelating resin Polymers 0.000 description 6
- 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 6
- 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 6
- 239000000843 powder Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 125000002091 cationic group Chemical group 0.000 description 5
- 230000002255 enzymatic effect Effects 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 230000033444 hydroxylation Effects 0.000 description 5
- 238000005805 hydroxylation reaction Methods 0.000 description 5
- 150000002596 lactones Chemical group 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
- 125000002843 carboxylic acid group Chemical group 0.000 description 4
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- 150000001875 compounds Chemical class 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 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 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000006243 chemical reaction Methods 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
- 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
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- YKYONYBAUNKHLG-UHFFFAOYSA-N propyl acetate Chemical compound CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 3
- 230000002000 scavenging effect Effects 0.000 description 3
- 238000003756 stirring 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
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- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
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- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 2
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- 150000001340 alkali metals Chemical class 0.000 description 2
- 239000006286 aqueous extract Substances 0.000 description 2
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- 229960005370 atorvastatin Drugs 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- NMJJFJNHVMGPGM-UHFFFAOYSA-N butyl formate Chemical compound CCCCOC=O NMJJFJNHVMGPGM-UHFFFAOYSA-N 0.000 description 2
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- 238000000576 coating method Methods 0.000 description 2
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 229960003765 fluvastatin Drugs 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
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- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
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- 238000004519 manufacturing process Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- BHIWKHZACMWKOJ-UHFFFAOYSA-N methyl isobutyrate Chemical compound COC(=O)C(C)C BHIWKHZACMWKOJ-UHFFFAOYSA-N 0.000 description 2
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- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
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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)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Diabetes (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Vascular 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)
- Pyrane Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23827800P | 2000-10-05 | 2000-10-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200302313B true ZA200302313B (en) | 2004-03-25 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200302313A ZA200302313B (en) | 2000-10-05 | 2003-03-25 | Pravastatin sodium substantially free of pravastatin lactone and epi-pravastatin, and compositions containing same. |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP1330245A4 (cs) |
| JP (6) | JP3737801B2 (cs) |
| KR (1) | KR20030059173A (cs) |
| CN (1) | CN1468098A (cs) |
| AU (1) | AU2002211462A1 (cs) |
| CA (1) | CA2422744A1 (cs) |
| CZ (1) | CZ20031166A3 (cs) |
| HR (1) | HRP20030347A2 (cs) |
| HU (1) | HUP0400913A2 (cs) |
| IL (1) | IL155194A0 (cs) |
| IS (1) | IS6766A (cs) |
| MX (1) | MXPA03002963A (cs) |
| NO (1) | NO20031532L (cs) |
| NZ (1) | NZ525631A (cs) |
| PL (1) | PL361230A1 (cs) |
| SK (1) | SK5232003A3 (cs) |
| WO (1) | WO2002030415A1 (cs) |
| ZA (1) | ZA200302313B (cs) |
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| EP1798214A3 (en) * | 1999-11-30 | 2007-08-01 | Teva Gyogyszergyár Zártköruen Muködo Részvenytarsaság | Process for recovering statin compounds from a fermentation broth |
| KR20030026920A (ko) * | 1999-11-30 | 2003-04-03 | 비오갈 기오기스제르갸르 알티. | 발효 브로스로부터 스타틴 화합물의 수집 방법 |
| SI1265604T1 (sl) * | 1999-11-30 | 2007-04-30 | Sag Teva Gyogyszergyar Zartkoe | Postopek za ponovno pridobivanje statinskih spojin iz fermentacije brozge |
| HUP0204005A3 (en) | 1999-12-14 | 2003-05-28 | Teva Gyogyszergyar Zartkoeruee | Novel forms of pravastatin sodium, process for their preparation and pharmaceutical compositions containing them |
| AU2002211462A1 (en) * | 2000-10-05 | 2002-04-22 | Teva Gyogyszergyar Reszvenytarsasag | Pravastatin sodium substantially free of pravastatin lactone and epi-pravastatin, and compositions containing same |
| 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 (en) * | 2003-02-25 | 2004-09-01 | Balkanpharma-Razgrad AD | Method for the isolation and purification of pravastatin sodium |
| 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 |
| TWI319707B (en) * | 2003-11-24 | 2010-01-21 | Method of purifying pravastatin | |
| EP1786414A4 (en) | 2004-08-06 | 2008-04-09 | Transform Pharmaceuticals Inc | NEW PHARMACEUTICAL STATIN COMPOSITIONS AND RELEVANT TREATMENT PROCEDURES |
| 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 |
| CN114031496A (zh) * | 2021-11-30 | 2022-02-11 | 广东蓝宝制药有限公司 | 一种高纯度普伐他汀1,1,3,3-四甲基丁胺的制备方法 |
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| US3378441A (en) * | 1963-10-17 | 1968-04-16 | S B Penick & Company | Tetraene antibiotic purification |
| JPS5221594B2 (cs) * | 1973-09-29 | 1977-06-11 | ||
| IT1059403B (it) * | 1975-02-07 | 1982-05-31 | Glaxo Lab Ltd | Procedimento per produrre acido clavulanico e suoi derivati nonche composizioni che lo contengono |
| US4231938A (en) * | 1979-06-15 | 1980-11-04 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
| MX7065E (es) * | 1980-06-06 | 1987-04-10 | Sankyo Co | Un procedimiento microbiologico para preparar derivados de ml-236b |
| JPS572240A (en) * | 1980-06-06 | 1982-01-07 | Sankyo Co Ltd | Ml-236b derivative |
| 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 |
| ATE159051T1 (de) * | 1994-03-31 | 1997-10-15 | Cultor Oy | Verfahren zur rückgewinnung von natamycin |
| 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 (en) * | 1997-05-07 | 1998-11-11 | Gist-Brocades B.V. | HMG-CoA reductase inhibitor preparation process |
| 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 |
| PL350317A1 (en) * | 1999-02-03 | 2002-12-02 | Inst Drug Res Ltd | Microbial process for preparing pravastatin |
| HUP9902352A1 (hu) * | 1999-07-12 | 2000-09-28 | Gyógyszerkutató Intézet Kft. | Eljárás pravasztatin mikrobiológiai előállítására |
| KR20030026920A (ko) * | 1999-11-30 | 2003-04-03 | 비오갈 기오기스제르갸르 알티. | 발효 브로스로부터 스타틴 화합물의 수집 방법 |
| AU2002211462A1 (en) * | 2000-10-05 | 2002-04-22 | Teva Gyogyszergyar Reszvenytarsasag | Pravastatin sodium substantially free of pravastatin lactone and epi-pravastatin, and compositions containing same |
-
2001
- 2001-10-05 AU AU2002211462A patent/AU2002211462A1/en not_active Abandoned
- 2001-10-05 IL IL15519401A patent/IL155194A0/xx unknown
- 2001-10-05 WO PCT/US2001/031230 patent/WO2002030415A1/en not_active Application Discontinuation
- 2001-10-05 CZ CZ20031166A patent/CZ20031166A3/cs unknown
- 2001-10-05 NZ NZ525631A patent/NZ525631A/en unknown
- 2001-10-05 CA CA002422744A patent/CA2422744A1/en not_active Abandoned
- 2001-10-05 PL PL01361230A patent/PL361230A1/xx unknown
- 2001-10-05 JP JP2002533858A patent/JP3737801B2/ja not_active Expired - Fee Related
- 2001-10-05 HU HU0400913A patent/HUP0400913A2/hu not_active IP Right Cessation
- 2001-10-05 SK SK523-2003A patent/SK5232003A3/sk unknown
- 2001-10-05 EP EP01979511A patent/EP1330245A4/en not_active Withdrawn
- 2001-10-05 KR KR10-2003-7004764A patent/KR20030059173A/ko not_active IP Right Cessation
- 2001-10-05 MX MXPA03002963A patent/MXPA03002963A/es not_active Application Discontinuation
- 2001-10-05 CN CNA018168604A patent/CN1468098A/zh active Pending
-
2003
- 2003-03-25 ZA ZA200302313A patent/ZA200302313B/en unknown
- 2003-04-01 IS IS6766A patent/IS6766A/is unknown
- 2003-04-04 NO NO20031532A patent/NO20031532L/no not_active Application Discontinuation
- 2003-05-02 HR HR20030347A patent/HRP20030347A2/xx not_active Application Discontinuation
-
2004
- 2004-09-24 JP JP2004278522A patent/JP2005013238A/ja not_active Withdrawn
-
2005
- 2005-08-18 JP JP2005237299A patent/JP2006036781A/ja active Pending
-
2009
- 2009-08-21 JP JP2009191951A patent/JP2009268479A/ja not_active Withdrawn
-
2013
- 2013-01-25 JP JP2013011711A patent/JP2013128486A/ja not_active Withdrawn
-
2015
- 2015-07-31 JP JP2015152088A patent/JP2015212300A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0400913A2 (en) | 2006-11-28 |
| IS6766A (is) | 2003-04-01 |
| JP2015212300A (ja) | 2015-11-26 |
| NZ525631A (en) | 2005-05-27 |
| PL361230A1 (en) | 2004-10-04 |
| CN1468098A (zh) | 2004-01-14 |
| JP2009268479A (ja) | 2009-11-19 |
| AU2002211462A1 (en) | 2002-04-22 |
| NO20031532D0 (no) | 2003-04-04 |
| JP2005013238A (ja) | 2005-01-20 |
| SK5232003A3 (en) | 2004-06-08 |
| JP2006036781A (ja) | 2006-02-09 |
| IL155194A0 (en) | 2003-11-23 |
| EP1330245A1 (en) | 2003-07-30 |
| CZ20031166A3 (cs) | 2004-04-14 |
| MXPA03002963A (es) | 2005-01-25 |
| JP2013128486A (ja) | 2013-07-04 |
| JP2004510817A (ja) | 2004-04-08 |
| JP3737801B2 (ja) | 2006-01-25 |
| CA2422744A1 (en) | 2002-04-18 |
| WO2002030415A1 (en) | 2002-04-18 |
| KR20030059173A (ko) | 2003-07-07 |
| NO20031532L (no) | 2003-04-04 |
| HRP20030347A2 (en) | 2005-04-30 |
| WO2002030415A9 (en) | 2002-10-31 |
| EP1330245A4 (en) | 2004-10-20 |
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