SK4532003A3 - Method of purifying plavastatin - Google Patents

Method of purifying plavastatin Download PDF

Info

Publication number: SK4532003A3
Authority: SK; Slovakia
Prior art keywords: pravastatin; purification; isolation; acceptable salt; pharmaceutically acceptable
Prior art date: 2000-10-16

Application number

SK453-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Nobunari Sugio

Shunshi Kojima

Yasuyuki Takamatsu

Minoru Hagisawa

Kiyoshi Hamano

Mutsuo Suzuki

Original Assignee

Sankyo Co

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.)

2000-10-16

Filing date

2001-10-15

Publication date

2003-10-07

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=18794392&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=SK4532003(A3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2001-10-15 Application filed by Sankyo Co filed Critical Sankyo Co

2003-10-07 Publication of SK4532003A3 publication Critical patent/SK4532003A3/sk

Links

238000000034 method Methods 0.000 title claims abstract description 121
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 claims abstract description 250
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 159
229960002965 pravastatin Drugs 0.000 claims abstract description 159
229960001495 pravastatin sodium Drugs 0.000 claims abstract description 84
239000012535 impurity Substances 0.000 claims abstract description 73
150000003839 salts Chemical class 0.000 claims abstract description 60
150000007522 mineralic acids Chemical class 0.000 claims abstract description 39
125000000217 alkyl group Chemical group 0.000 claims abstract description 36
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 36
150000007529 inorganic bases Chemical class 0.000 claims abstract description 33
239000003960 organic solvent Substances 0.000 claims abstract description 33
239000000203 mixture Substances 0.000 claims abstract description 19
238000000746 purification Methods 0.000 claims description 99
238000002955 isolation Methods 0.000 claims description 83
150000001875 compounds Chemical class 0.000 claims description 59
238000000354 decomposition reaction Methods 0.000 claims description 54
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 32
238000000605 extraction Methods 0.000 claims description 29
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 16
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 12
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 34
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 32
239000000243 solution Substances 0.000 description 28
238000004128 high performance liquid chromatography Methods 0.000 description 26
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 20
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
YKYONYBAUNKHLG-UHFFFAOYSA-N propyl acetate Chemical compound CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 17
239000002904 solvent Substances 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 14
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 14
239000000706 filtrate Substances 0.000 description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
230000035484 reaction time Effects 0.000 description 10
-1 and the like Chemical compound 0.000 description 9
229940125904 compound 1 Drugs 0.000 description 8
238000002425 crystallisation Methods 0.000 description 8
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238000003756 stirring Methods 0.000 description 8
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238000000855 fermentation Methods 0.000 description 7
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239000012046 mixed solvent Substances 0.000 description 7
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
150000001298 alcohols Chemical class 0.000 description 5
238000001914 filtration Methods 0.000 description 5
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KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
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230000015556 catabolic process Effects 0.000 description 4
238000006731 degradation reaction Methods 0.000 description 4
238000002086 displacement chromatography Methods 0.000 description 4
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239000012442 inert solvent Substances 0.000 description 4
PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 4
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
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 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
238000001514 detection method Methods 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
239000007788 liquid Substances 0.000 description 3
229960004844 lovastatin Drugs 0.000 description 3
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 3
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 3
230000000813 microbial effect Effects 0.000 description 3
244000005700 microbiome Species 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
230000003287 optical effect Effects 0.000 description 3
238000002390 rotary evaporation Methods 0.000 description 3
238000000926 separation method Methods 0.000 description 3
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-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
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
150000008044 alkali metal hydroxides Chemical class 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
230000000052 comparative effect Effects 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
238000004821 distillation Methods 0.000 description 2
239000003814 drug Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000000047 product Substances 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
230000006798 recombination Effects 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
239000012266 salt solution Substances 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
229960002855 simvastatin Drugs 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
239000011780 sodium chloride Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
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229940124597 therapeutic agent Drugs 0.000 description 2
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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 1
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 1
125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
125000005916 2-methylpentyl group Chemical group 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
125000005917 3-methylpentyl group Chemical group 0.000 description 1
206010067484 Adverse reaction Diseases 0.000 description 1
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 1
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 1
DBAMUTGXJAWDEA-UHFFFAOYSA-N Butynol Chemical compound CCC#CO DBAMUTGXJAWDEA-UHFFFAOYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
238000010268 HPLC based assay Methods 0.000 description 1
208000031226 Hyperlipidaemia Diseases 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
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241000228153 Penicillium citrinum Species 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
229940123934 Reductase inhibitor Drugs 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
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230000002378 acidificating effect Effects 0.000 description 1
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150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
150000008041 alkali metal carbonates Chemical class 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
239000012670 alkaline solution Substances 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
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KJKPYONSOHIHQW-UHFFFAOYSA-N butyl acetate;propyl acetate Chemical compound CCCOC(C)=O.CCCCOC(C)=O KJKPYONSOHIHQW-UHFFFAOYSA-N 0.000 description 1
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GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
229910052808 lithium carbonate Inorganic materials 0.000 description 1
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SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
229910000032 lithium hydrogen carbonate Inorganic materials 0.000 description 1
JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 description 1
HQRPHMAXFVUBJX-UHFFFAOYSA-M lithium;hydrogen carbonate Chemical compound [Li+].OC([O-])=O HQRPHMAXFVUBJX-UHFFFAOYSA-M 0.000 description 1
230000005923 long-lasting effect Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000002245 particle Substances 0.000 description 1
125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
229960002797 pitavastatin Drugs 0.000 description 1
VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
229940090181 propyl acetate Drugs 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
OVYTZAASVAZITK-UHFFFAOYSA-M sodium;ethanol;hydroxide Chemical compound [OH-].[Na+].CCO OVYTZAASVAZITK-UHFFFAOYSA-M 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000003643 water by type Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- 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
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
- C12P17/06—Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein
- 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
- 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
- C07C67/58—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
- 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
- C07C67/60—Separation; Purification; Stabilisation; Use of additives by treatment giving rise to chemical modification
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/22—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety
- C07C69/33—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety esterified with hydroxy compounds having more than three hydroxy groups
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/62—Carboxylic acid esters
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/26—All rings being cycloaliphatic the ring system containing ten carbon atoms
- C07C2602/28—Hydrogenated naphthalenes

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
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Wood Science & Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
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Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Biotechnology (AREA)
Genetics & Genomics (AREA)
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Pharmacology & Pharmacy (AREA)
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Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (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)

SK453-2003A 2000-10-16 2001-10-15 Method of purifying plavastatin SK4532003A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP2000315256A JP3236282B1 (ja)	2000-10-16	2000-10-16	プラバスタチンを精製する方法
PCT/JP2001/009045 WO2002032848A1 (fr)	2000-10-16	2001-10-15	Procede de purification de pravastatine

Publications (1)

Publication Number	Publication Date
SK4532003A3 true SK4532003A3 (en)	2003-10-07

Family

ID=18794392

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK453-2003A SK4532003A3 (en)	2000-10-16	2001-10-15	Method of purifying plavastatin

Country Status (19)

Country	Link
US (1)	US20030216596A1 (fr)
EP (4)	EP1327626A4 (fr)
JP (1)	JP3236282B1 (fr)
KR (1)	KR20030042018A (fr)
CN (4)	CN1868996A (fr)
AU (1)	AU2001294258A1 (fr)
BR (1)	BR0114681A (fr)
CA (1)	CA2425883A1 (fr)
CZ (1)	CZ20031052A3 (fr)
HU (1)	HUP0303106A3 (fr)
IL (1)	IL155360A0 (fr)
MX (1)	MXPA03003347A (fr)
NO (1)	NO20031739L (fr)
NZ (3)	NZ536891A (fr)
PL (1)	PL360934A1 (fr)
RU (2)	RU2260582C2 (fr)
SK (1)	SK4532003A3 (fr)
WO (1)	WO2002032848A1 (fr)
ZA (1)	ZA200302966B (fr)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP3422791B2 (ja)	2002-08-06	2003-06-30	三共株式会社	プラバスタチンの単離・精製方法
TW589178B (en) *	2003-02-21	2004-06-01	China Chemical & Pharmaceutica	A novel industrial process to obtain pravastatin sodium of high purity
EP1452519A1 (fr) *	2003-02-25	2004-09-01	Balkanpharma-Razgrad AD	Procédé d'isolation et purification de pravastatine sodique
US20090042979A1 (en) *	2004-08-06	2009-02-12	Transform Pharmaceuticals Inc.	Novel Statin Pharmaceutical Compositions and Related Methods of Treatment
WO2006017692A2 (fr) *	2004-08-06	2006-02-16	Transform Pharmaceuticals, Inc.	Nouvelles preparations de fenofibrate et methodes de traitement associees
KR20070038553A (ko) *	2004-08-06	2007-04-10	트렌스폼 파마수티컬스 인코퍼레이티드	신규한 스타틴 약제학적 조성물 및 관련된 치료방법
CN100361954C (zh) *	2005-05-16	2008-01-16	天津市冠东科技有限公司	制备普伐他汀结晶体的干燥方法
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
JP2012507299A (ja) *	2008-10-31	2012-03-29	バイオジェン・アイデック・エムエイ・インコーポレイテッド	Ｌｉｇｈｔ標的分子およびその使用
CN109796333B (zh) *	2019-01-25	2021-04-09	北大方正集团有限公司	一种从发酵液中提取纯化普伐他汀钠的方法
CN112778120B (zh) *	2019-11-08	2024-05-17	上海现代制药股份有限公司	一种降血脂类药物氧化杂质的制备方法
CN119915919A (zh) *	2023-10-31	2025-05-02	上海现代制药股份有限公司	普伐他汀有关物质的检测方法
CN119915920A (zh) *	2023-10-31	2025-05-02	上海现代制药股份有限公司	普伐他汀有关物质的检测方法

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MX7065E (es) *	1980-06-06	1987-04-10	Sankyo Co	Un procedimiento microbiologico para preparar derivados de ml-236b
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
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
IL108432A (en) *	1993-01-29	1997-09-30	Sankyo Co	DERIVATIVES OF 3, 5-DIHYDROXY-7- £1, 2, 6, 7, 8, 8a-HEXAHYDRO-2- METHYL-8- (SUBSTITUTED ALKANOYLOXY)-1-NAPHTHYL\| HEPTANOIC ACID AND THEIR LACTONES, THEIR PREPARATION, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
WO1997006128A1 (fr) *	1995-08-03	1997-02-20	Gist-Brocades B.V.	Processus selectif de desacylation de composes acyles
SI9800046A (sl)	1998-02-18	1999-08-31	LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d.	Postopek za pridobivanje inhibitorjev HMG-CoA reduktaze visoke čistosti
SI20305A (sl) *	1999-08-06	2001-02-28	LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d.	Kristali natrijeve soli pravastatina
SI20072A (sl)	1998-09-18	2000-04-30	LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d.	Postopek za pridobivanje inhibitorjev HMG-CoA reduktaze
JP2000279174A (ja)	1999-03-30	2000-10-10	Bml Inc	ヒトｌｄｌレセプターに対するモノクローナル抗体及びこれを用いる家族性高脂血症の判定方法
HUP9902352A1 (hu) *	1999-07-12	2000-09-28	Gyógyszerkutató Intézet Kft.	Eljárás pravasztatin mikrobiológiai előállítására
HRP20030347A2 (en) *	2000-10-05	2005-04-30	Teva Gy�gyszergy�r R�szv�nyt�rsas�g	Pravastatin sodium substantially free of pravastatin lactone and epi-pravastatin, and compositions containing same

2000
- 2000-10-16 JP JP2000315256A patent/JP3236282B1/ja not_active Expired - Lifetime
2001
- 2001-10-15 CZ CZ20031052A patent/CZ20031052A3/cs unknown
- 2001-10-15 EP EP01974858A patent/EP1327626A4/fr not_active Withdrawn
- 2001-10-15 CN CNA2005100700673A patent/CN1868996A/zh active Pending
- 2001-10-15 EP EP04027245A patent/EP1514862A1/fr not_active Withdrawn
- 2001-10-15 NZ NZ536891A patent/NZ536891A/en unknown
- 2001-10-15 BR BR0114681-5A patent/BR0114681A/pt not_active IP Right Cessation
- 2001-10-15 HU HU0303106A patent/HUP0303106A3/hu unknown
- 2001-10-15 CN CNA2005100712967A patent/CN1690037A/zh active Pending
- 2001-10-15 CN CNA01820712XA patent/CN1481353A/zh active Pending
- 2001-10-15 NZ NZ525256A patent/NZ525256A/en unknown
- 2001-10-15 EP EP04027246A patent/EP1514863A1/fr not_active Withdrawn
- 2001-10-15 WO PCT/JP2001/009045 patent/WO2002032848A1/fr not_active Ceased
- 2001-10-15 MX MXPA03003347A patent/MXPA03003347A/es unknown
- 2001-10-15 CN CNA2005100700688A patent/CN1679535A/zh active Pending
- 2001-10-15 AU AU2001294258A patent/AU2001294258A1/en not_active Abandoned
- 2001-10-15 KR KR10-2003-7005271A patent/KR20030042018A/ko not_active Withdrawn
- 2001-10-15 NZ NZ536892A patent/NZ536892A/en unknown
- 2001-10-15 RU RU2003110580/04A patent/RU2260582C2/ru not_active IP Right Cessation
- 2001-10-15 PL PL01360934A patent/PL360934A1/xx not_active Application Discontinuation
- 2001-10-15 IL IL15536001A patent/IL155360A0/xx unknown
- 2001-10-15 SK SK453-2003A patent/SK4532003A3/sk unknown
- 2001-10-15 CA CA002425883A patent/CA2425883A1/fr not_active Abandoned
- 2001-10-15 EP EP04027244A patent/EP1522589A1/fr not_active Withdrawn
2003
- 2003-04-15 NO NO20031739A patent/NO20031739L/no not_active Application Discontinuation
- 2003-04-15 ZA ZA200302966A patent/ZA200302966B/en unknown
- 2003-04-16 US US10/417,062 patent/US20030216596A1/en not_active Abandoned
2005
- 2005-05-04 RU RU2005113661/04A patent/RU2005113661A/ru not_active Application Discontinuation

Also Published As

Publication number	Publication date
CN1481353A (zh)	2004-03-10
EP1327626A1 (fr)	2003-07-16
WO2002032848A1 (fr)	2002-04-25
BR0114681A (pt)	2003-12-09
CZ20031052A3 (cs)	2003-09-17
EP1514862A1 (fr)	2005-03-16
NZ536891A (en)	2005-05-27
US20030216596A1 (en)	2003-11-20
CN1679535A (zh)	2005-10-12
PL360934A1 (en)	2004-09-20
NZ536892A (en)	2005-05-27
KR20030042018A (ko)	2003-05-27
HUP0303106A2 (hu)	2003-12-29
AU2001294258A1 (en)	2002-04-29
MXPA03003347A (es)	2003-06-19
NO20031739D0 (no)	2003-04-15
HUP0303106A3 (en)	2004-10-28
CA2425883A1 (fr)	2003-04-15
JP2002121174A (ja)	2002-04-23
EP1327626A4 (fr)	2004-08-18
NO20031739L (no)	2003-06-13
CN1868996A (zh)	2006-11-29
IL155360A0 (en)	2003-11-23
CN1690037A (zh)	2005-11-02
EP1514863A1 (fr)	2005-03-16
NZ525256A (en)	2005-01-28
RU2260582C2 (ru)	2005-09-20
EP1522589A1 (fr)	2005-04-13
ZA200302966B (en)	2004-07-15
RU2005113661A (ru)	2006-11-10
JP3236282B1 (ja)	2001-12-10

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