SK5232003A3 - 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 PDF

Info

Publication number: SK5232003A3
Authority: SK; Slovakia
Prior art keywords: pravastatin; sodium; salt; solution; pravastatin sodium
Prior art date: 2000-10-05

Application number

SK523-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Vilmos Keri

Lajos Deak

Ilona Forgacs

Csaba Szabo

Arvai Edit Nagyne

Original Assignee

Biogal Gyogyszergyar

Priority date (The priority date 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 date listed.)

2000-10-05

Filing date

2001-10-05

Publication date

2004-06-08

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22897222&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=SK5232003(A3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2001-10-05 Application filed by Biogal Gyogyszergyar filed Critical Biogal Gyogyszergyar

2004-06-08 Publication of SK5232003A3 publication Critical patent/SK5232003A3/sk

Links

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 abstract description 175
229960002965 pravastatin Drugs 0.000 title claims abstract description 118
229960001495 pravastatin sodium Drugs 0.000 title claims abstract description 70
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 abstract description 14
239000000203 mixture Substances 0.000 title claims description 27
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 abstract description 116
238000000034 method Methods 0.000 claims abstract description 31
150000003863 ammonium salts Chemical class 0.000 claims abstract description 29
238000000855 fermentation Methods 0.000 claims abstract description 23
230000004151 fermentation Effects 0.000 claims abstract description 23
230000008569 process Effects 0.000 claims abstract description 10
150000003839 salts Chemical class 0.000 claims abstract description 9
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 77
239000000243 solution Substances 0.000 claims description 73
-1 pravastatin salt cation Chemical class 0.000 claims description 47
GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 claims description 37
FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 claims description 37
OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 claims description 37
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 36
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
239000007787 solid Substances 0.000 claims description 22
235000019270 ammonium chloride Nutrition 0.000 claims description 17
239000013078 crystal Substances 0.000 claims description 17
238000002425 crystallisation Methods 0.000 claims description 15
230000008025 crystallization Effects 0.000 claims description 15
239000003960 organic solvent Substances 0.000 claims description 15
150000001412 amines Chemical class 0.000 claims description 13
239000007864 aqueous solution Substances 0.000 claims description 12
238000001953 recrystallisation Methods 0.000 claims description 12
239000003456 ion exchange resin Substances 0.000 claims description 11
229920003303 ion-exchange polymer Polymers 0.000 claims description 11
229910052783 alkali metal Inorganic materials 0.000 claims description 10
239000011734 sodium Substances 0.000 claims description 10
229910052708 sodium Inorganic materials 0.000 claims description 10
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
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 7
239000012296 anti-solvent Substances 0.000 claims description 6
229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 5
239000002552 dosage form Substances 0.000 claims description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 4
238000004108 freeze drying Methods 0.000 claims description 4
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
230000002378 acidificating effect Effects 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
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
239000008194 pharmaceutical composition Substances 0.000 claims 2
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 claims 2
238000009472 formulation Methods 0.000 claims 1
238000000605 extraction Methods 0.000 abstract description 18
150000001875 compounds Chemical class 0.000 abstract description 8
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 20
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
239000002253 acid Substances 0.000 description 13
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
238000001914 filtration Methods 0.000 description 9
238000002955 isolation Methods 0.000 description 9
239000000047 product Substances 0.000 description 9
239000002904 solvent Substances 0.000 description 9
238000004128 high performance liquid chromatography Methods 0.000 description 8
229920001467 poly(styrenesulfonates) Polymers 0.000 description 8
239000011347 resin Substances 0.000 description 8
229920005989 resin Polymers 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
229910021529 ammonia Inorganic materials 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
159000000000 sodium salts Chemical class 0.000 description 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
239000000843 powder Substances 0.000 description 6
239000003826 tablet Substances 0.000 description 6
239000006286 aqueous extract Substances 0.000 description 5
229920001429 chelating resin Polymers 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
239000000546 pharmaceutical excipient Substances 0.000 description 5
238000000746 purification Methods 0.000 description 5
239000002689 soil Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-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
235000011114 ammonium hydroxide Nutrition 0.000 description 4
125000002843 carboxylic acid group Chemical group 0.000 description 4
239000003729 cation exchange resin Substances 0.000 description 4
229940023913 cation exchange resins Drugs 0.000 description 4
150000001768 cations Chemical class 0.000 description 4
239000001913 cellulose Substances 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
229940079593 drug Drugs 0.000 description 4
239000003814 drug Substances 0.000 description 4
230000002255 enzymatic effect Effects 0.000 description 4
150000002596 lactones Chemical group 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
239000000908 ammonium hydroxide Substances 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000002775 capsule Substances 0.000 description 3
235000010980 cellulose Nutrition 0.000 description 3
229920002678 cellulose Polymers 0.000 description 3
229920001577 copolymer Polymers 0.000 description 3
239000002702 enteric coating Substances 0.000 description 3
238000009505 enteric coating Methods 0.000 description 3
239000007789 gas Substances 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 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
239000003791 organic solvent mixture Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
238000001556 precipitation Methods 0.000 description 3
YKYONYBAUNKHLG-UHFFFAOYSA-N propyl acetate Chemical compound CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 3
238000005185 salting out Methods 0.000 description 3
229910001415 sodium ion Inorganic materials 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
TUZYXOIXSAXUGO-JFBQIPGGSA-N (3r,5r)-7-[(2s,6s,8s,8ar)-6-hydroxy-2-methyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C1=C[C@H](C)C(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-JFBQIPGGSA-N 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
229920002134 Carboxymethyl cellulose Polymers 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
FFOPEPMHKILNIT-UHFFFAOYSA-N Isopropyl butyrate Chemical compound CCCC(=O)OC(C)C FFOPEPMHKILNIT-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
229920000881 Modified starch Polymers 0.000 description 2
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
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000003125 aqueous solvent Substances 0.000 description 2
229960005370 atorvastatin Drugs 0.000 description 2
239000002585 base Substances 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
DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
NMJJFJNHVMGPGM-UHFFFAOYSA-N butyl formate Chemical compound CCCCOC=O NMJJFJNHVMGPGM-UHFFFAOYSA-N 0.000 description 2
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
239000008112 carboxymethyl-cellulose Substances 0.000 description 2
239000003610 charcoal Substances 0.000 description 2
239000013522 chelant Substances 0.000 description 2
239000011248 coating agent Substances 0.000 description 2
238000000576 coating method Methods 0.000 description 2
239000002274 desiccant Substances 0.000 description 2
150000002148 esters Chemical class 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
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
239000008187 granular material Substances 0.000 description 2
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
239000012535 impurity Substances 0.000 description 2
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
239000007788 liquid Substances 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
229910003002 lithium salt Inorganic materials 0.000 description 2
PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
229960004844 lovastatin Drugs 0.000 description 2
QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
BHIWKHZACMWKOJ-UHFFFAOYSA-N methyl isobutyrate Chemical compound COC(=O)C(C)C BHIWKHZACMWKOJ-UHFFFAOYSA-N 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 2
229960002855 simvastatin Drugs 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000008247 solid mixture Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000000126 substance Substances 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
HNAGHMKIPMKKBB-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carboxamide Chemical compound C1C(C(=O)N)CCN1CC1=CC=CC=C1 HNAGHMKIPMKKBB-UHFFFAOYSA-N 0.000 description 1
YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
HFZLSTDPRQSZCQ-UHFFFAOYSA-N 1-pyrrolidin-3-ylpyrrolidine Chemical compound C1CCCN1C1CNCC1 HFZLSTDPRQSZCQ-UHFFFAOYSA-N 0.000 description 1
PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
AVMSWPWPYJVYKY-UHFFFAOYSA-N 2-Methylpropyl formate Chemical compound CC(C)COC=O AVMSWPWPYJVYKY-UHFFFAOYSA-N 0.000 description 1
XZXYQEHISUMZAT-UHFFFAOYSA-N 2-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol Chemical compound CC1=CC=C(O)C(CC=2C(=CC=C(C)C=2)O)=C1 XZXYQEHISUMZAT-UHFFFAOYSA-N 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
239000004254 Ammonium phosphate Substances 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
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238000009666 routine test Methods 0.000 description 1
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239000002278 tabletting lubricant 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
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238000004809 thin layer chromatography Methods 0.000 description 1
238000000825 ultraviolet detection Methods 0.000 description 1
238000005292 vacuum distillation Methods 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

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Heart & Thoracic Surgery (AREA)
Epidemiology (AREA)
Cardiology (AREA)
Crystallography & Structural Chemistry (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Emergency Medicine (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyrane Compounds (AREA)

SK523-2003A 2000-10-05 2001-10-05 Pravastatin sodium substantially free of pravastatin lactone and epi-pravastatin, and compositions containing same SK5232003A3 (en)

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

Publications (1)

Publication Number	Publication Date
SK5232003A3 true SK5232003A3 (en)	2004-06-08

Family

ID=22897222

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK523-2003A SK5232003A3 (en)	2000-10-05	2001-10-05	Pravastatin sodium substantially free of pravastatin lactone and epi-pravastatin, and compositions containing same

Country Status (18)

Country	Link
EP (1)	EP1330245A4 (ja)
JP (6)	JP3737801B2 (ja)
KR (1)	KR20030059173A (ja)
CN (1)	CN1468098A (ja)
AU (1)	AU2002211462A1 (ja)
CA (1)	CA2422744A1 (ja)
CZ (1)	CZ20031166A3 (ja)
HR (1)	HRP20030347A2 (ja)
HU (1)	HUP0400913A2 (ja)
IL (1)	IL155194A0 (ja)
IS (1)	IS6766A (ja)
MX (1)	MXPA03002963A (ja)
NO (1)	NO20031532L (ja)
NZ (1)	NZ525631A (ja)
PL (1)	PL361230A1 (ja)
SK (1)	SK5232003A3 (ja)
WO (1)	WO2002030415A1 (ja)
ZA (1)	ZA200302313B (ja)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1481674B1 (en) *	1999-11-30	2008-01-02	TEVA Gyógyszergyár Zártkörüen Müködö Részvénytársaság	Process for recovering statin compounds from a fermentation broth
RU2002114072A (ru) *	1999-11-30	2004-07-20	Биогал Джиоджисзерджиар РТ (HU)	Способ выделения соединений статина из ферментационного бульона
EP1798214A3 (en) *	1999-11-30	2007-08-01	Teva Gyogyszergyár Zártköruen Muködo Részvenytarsaság	Process for recovering statin compounds from a fermentation broth
CA2394200C (en)	1999-12-14	2006-10-03	Biogal Gyogyszergyar Rt.	Novel forms of pravastatin sodium
CZ20031166A3 (cs) *	2000-10-05	2004-04-14	Biogal Gyogyszergyar Rt	Sodná sůl pravastatinu, která v podstatě neobsahuje pravastatin lakton a epi-pravastatin a kompozice na její bázi
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2003
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2004
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Also Published As

Publication number	Publication date
IL155194A0 (en)	2003-11-23
WO2002030415A9 (en)	2002-10-31
PL361230A1 (en)	2004-10-04
HUP0400913A2 (en)	2006-11-28
HRP20030347A2 (en)	2005-04-30
NO20031532D0 (no)	2003-04-04
CA2422744A1 (en)	2002-04-18
ZA200302313B (en)	2004-03-25
EP1330245A1 (en)	2003-07-30
KR20030059173A (ko)	2003-07-07
WO2002030415A1 (en)	2002-04-18
CZ20031166A3 (cs)	2004-04-14
AU2002211462A1 (en)	2002-04-22
EP1330245A4 (en)	2004-10-20
JP2006036781A (ja)	2006-02-09
JP2013128486A (ja)	2013-07-04
JP3737801B2 (ja)	2006-01-25
MXPA03002963A (es)	2005-01-25
CN1468098A (zh)	2004-01-14
JP2005013238A (ja)	2005-01-20
NO20031532L (no)	2003-04-04
NZ525631A (en)	2005-05-27
JP2004510817A (ja)	2004-04-08
JP2015212300A (ja)	2015-11-26
IS6766A (is)	2003-04-01
JP2009268479A (ja)	2009-11-19

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