DK2318365T3 - Hidtil ukendte polymorfe former af perindopril (l)-arginin og fremgangsmåde til fremstilling heraf - Google Patents
Hidtil ukendte polymorfe former af perindopril (l)-arginin og fremgangsmåde til fremstilling heraf Download PDFInfo
- Publication number
- DK2318365T3 DK2318365T3 DK09769810.4T DK09769810T DK2318365T3 DK 2318365 T3 DK2318365 T3 DK 2318365T3 DK 09769810 T DK09769810 T DK 09769810T DK 2318365 T3 DK2318365 T3 DK 2318365T3
- Authority
- DK
- Denmark
- Prior art keywords
- perindopril
- arginine
- polymorphic form
- solvent
- preparation
- Prior art date
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- RYCSJJXKEWBUTI-YDYAIEMNSA-N perindopril arginine Chemical compound OC(=O)[C@@H](N)CCCNC(N)=N.C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 RYCSJJXKEWBUTI-YDYAIEMNSA-N 0.000 title claims description 180
- 238000000034 method Methods 0.000 title claims description 53
- 230000008569 process Effects 0.000 title claims description 46
- 238000002360 preparation method Methods 0.000 title description 45
- 239000002904 solvent Substances 0.000 claims description 48
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 27
- 239000002253 acid Substances 0.000 claims description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 19
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 18
- 239000012296 anti-solvent Substances 0.000 claims description 16
- 238000010992 reflux Methods 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 11
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- -1 acetonitrile Chemical class 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 8
- 238000002955 isolation Methods 0.000 claims 4
- 229930064664 L-arginine Natural products 0.000 claims 2
- 235000014852 L-arginine Nutrition 0.000 claims 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims 2
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 150000002430 hydrocarbons Chemical group 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 150000002500 ions Chemical class 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 229960002582 perindopril Drugs 0.000 description 39
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000007787 solid Substances 0.000 description 21
- 239000003960 organic solvent Substances 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 238000001907 polarising light microscopy Methods 0.000 description 9
- 150000003839 salts Chemical class 0.000 description 8
- 239000004475 Arginine Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 7
- 230000009477 glass transition Effects 0.000 description 7
- 238000001144 powder X-ray diffraction data Methods 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000002002 slurry Substances 0.000 description 6
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical class CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 229960003076 perindopril arginine Drugs 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000004626 scanning electron microscopy Methods 0.000 description 5
- 238000001694 spray drying Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 150000001483 arginine derivatives Chemical class 0.000 description 4
- 238000010533 azeotropic distillation Methods 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 238000000113 differential scanning calorimetry Methods 0.000 description 4
- 150000004677 hydrates Chemical class 0.000 description 4
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 4
- IYNMDWMQHSMDDE-MHXJNQAMSA-N perindopril erbumine Chemical class CC(C)(C)N.C1CCC[C@@H]2N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H](C(O)=O)C[C@@H]21 IYNMDWMQHSMDDE-MHXJNQAMSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 3
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 150000002688 maleic acid derivatives Chemical class 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- KFUSEUYYWQURPO-UHFFFAOYSA-N 1,2-dichloroethene Chemical compound ClC=CCl KFUSEUYYWQURPO-UHFFFAOYSA-N 0.000 description 1
- YVCVYCSAAZQOJI-JHQYFNNDSA-N 4'-demethylepipodophyllotoxin Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YVCVYCSAAZQOJI-JHQYFNNDSA-N 0.000 description 1
- 0 CCCCCC=*CCCC*CCCCCCC*(C)N(C)CC Chemical compound CCCCCC=*CCCC*CCCCCCC*(C)N(C)CC 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 229940062352 aceon Drugs 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000011146 organic particle Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229960003929 perindopril erbumine Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002076 thermal analysis method Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Claims (13)
1. Polymorf form γ af Perindopril (L)-Arginin kendetegnet ved et røntgenpulverdiffraktionsmønster med toppe ved 4,21, 7,87, 13,19, 14,12, 17,60, 20,15 ± 0,2 grad 2-theta.
2. Polymorf form γ ifølge krav 1, der har en krystalliseringsgrad på under 60 %.
3. Fremgangsmåde til fremstilling af den polymorfe form γ af Perindopril (L)-Arginin ifølge krav 1, hvilken fremgangsmåde omfatter følgende trin: a) opløsning af Perindoprilfri syre i vand, b) tilsætning af L-Arginin, c) Ijemelse af opløsningsmidlet og d) isolering af den polymorfe form γ af Perindopril (L)-Arginin.
4. Fremgangsmåde til fremstilling af den polymorfe form γ af Perindopril (L)-Arginin ifølge krav 1, hvilken fremgangsmåde omfatter følgende trin: a) opløsning af Perindopril L-Arginin i et opløsningsmiddel, b) tilsætning af antiopløsningsmiddel, c) isolering af den polymorfe form γ af Perindopril (L)-Arginin.
5. Fremgangsmåde til fremstilling af den polymorfe form γ af Perindopril (L)-Arginin ifølge krav 1, hvilken fremgangsmåde omfatter følgende trin: a) suspension af Perindoprilfri syre og L- Arginin i et opløsningsmiddel, b) opvarmning af reaktionsmassen til en refluxtemperatur, c) tilsætning af antiopløsningsmiddel og d) isolering af den polymorfe form γ af Perindopril (L)-Arginin.
6. Fremgangsmåde til fremstilling af den polymorfe form γ af Perindopril (L)-Arginin ifølge krav 1, hvilken fremgangsmåde omfatter følgende trin: a) opløsning af Perindoprilfri syre og (L)-Arginin i vand, b) tilsætning af første opløsningsmiddel, c) nedkøling af reaktionsblandingen, d) tilsætning af andet opløsningsmiddel og e) isolering af den polymorfe form γ af Perindopril (L)-Arginin.
7. Fremgangsmåde til fremstilling af den polymorfe form γ af Perindopril (L)-Arginin ifølge krav 1, hvilken fremgangsmåde omfatter følgende trin: a) opløsning af Perindoprilfri syre i blanding af opløsningsmidler, b) tilsætning af opløsningen af (L)-Arginin i vand øg c) isølering af den polymorfe form y af Perindopril (L)-Arginin.
8. Fremgangsmåde til fremstilling af den polymorfe form y af Perindopril (L)-Arginin ifølge krav 1, hvilken fremgangsmåde omfatter følgende trin: a) suspension af Perindopril (L)-Arginin i et opløsningsmiddel, b) ømrøring af suspensiønen fra trin (a) ved mellem 20 til 115° C øg c) isølering af den pølymørfe form γ af Perindopril (L)-Arginin.
9. Fremgangsmåde ifølge krav 8, hvor opløsningsmidlet er udvalgt fra carbønhydrider, såsøm toluen, pentan, n-heptan, cyclohexan, n-hexan eller nitriler, såsom acetonitril, eller blandinger deraf
10. Fremgangsmåde til fremstilling af den polymorfe form γ af Perindopril (L)-Arginin ifølge krav 1, hvilken fremgangsmåde omfatter følgende trin: a) suspension af Perindopril (L)-Arginin i et opløsningsmiddel, b) azeotrop destillering af suspensiønen fra trin (a) ved en temperatur på ca. 80-110 °C, c) tilsætning af antiopløsningsmiddel øg d) isolering af den polymorfe form γ af Perindopril (L)-Arginin.
11. Fremgangsmåde ifølge krav 10, hvor opløsningsmidlet er toluen.
12. Fremgangsmåde ifølge krav 10, hvor antiopløsningsmidlet er acetonitril.
13. Fremgangsmåde til fremstilling af den polymorfe form y af Perindopril (L)-Arginin ifølge krav 1 ved at eksponere den amorfe form af Perindopril (L)-Arginin for en relativ fugtighed på ca. 90 % i adskillige timer.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1535CH2008 | 2008-06-24 | ||
| PCT/IN2009/000357 WO2009157018A2 (en) | 2008-06-24 | 2009-06-22 | Novel polymorphic forms of perindopril (l)-arginine and process for the preparation thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2318365T3 true DK2318365T3 (da) | 2015-11-23 |
Family
ID=41203736
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK09769810.4T DK2318365T3 (da) | 2008-06-24 | 2009-06-22 | Hidtil ukendte polymorfe former af perindopril (l)-arginin og fremgangsmåde til fremstilling heraf |
Country Status (13)
| Country | Link |
|---|---|
| US (3) | US8686161B2 (da) |
| EP (2) | EP2318365B1 (da) |
| AU (1) | AU2009263737B2 (da) |
| CA (2) | CA2729604C (da) |
| CY (1) | CY1116930T1 (da) |
| DK (1) | DK2318365T3 (da) |
| ES (1) | ES2552653T3 (da) |
| HR (1) | HRP20151208T1 (da) |
| HU (1) | HUE025982T2 (da) |
| PL (1) | PL2318365T3 (da) |
| PT (1) | PT2318365E (da) |
| SI (1) | SI2318365T1 (da) |
| WO (1) | WO2009157018A2 (da) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2897866B1 (fr) | 2006-02-28 | 2008-04-18 | Servier Lab | Forme cristalline alpha du sel d'arginine du perindopril, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| DK2318365T3 (da) | 2008-06-24 | 2015-11-23 | Mylan Lab Ltd | Hidtil ukendte polymorfe former af perindopril (l)-arginin og fremgangsmåde til fremstilling heraf |
| AU2009212902A1 (en) * | 2008-09-03 | 2010-03-18 | Apotex Pharmachem Inc. | Amorphous form of an L-arginine salt of perindopril and processes of preparation thereof |
| FR2985512B1 (fr) * | 2012-01-05 | 2014-06-20 | Servier Lab | Procede de preparation du sel de l-arginine du perindopril |
| FR2985511B1 (fr) * | 2012-01-05 | 2014-01-03 | Servier Lab | Forme cristalline delta du sel d'arginine du perindopril, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| CN103172696B (zh) * | 2012-12-19 | 2014-12-17 | 宁波美诺华药业股份有限公司 | 一种γ晶型的培哚普利精氨酸盐的制备方法 |
| WO2016178591A2 (en) | 2015-05-05 | 2016-11-10 | Gene Predit, Sa | Genetic markers and treatment of male obesity |
| PH12018502155B1 (en) | 2016-04-20 | 2024-03-27 | Servier Lab | Pharmaceutical composition comprising a beta blocker, a converting enzyme inhibitor and an antihypertensive or an nsaid |
| CN109725022A (zh) * | 2018-12-27 | 2019-05-07 | 湖南科技大学 | 一种结合水含量的快速测量方法 |
| EP3842035A1 (en) | 2019-12-23 | 2021-06-30 | KRKA, d.d., Novo mesto | Composition for the preparation of perindopril arginine granules, a method for their preparation and pharmaceutical composition comprising the granules |
| CN112047999B (zh) * | 2020-09-18 | 2022-12-02 | 天津力生制药股份有限公司 | 一种γ晶型的精氨酸培哚普利盐的制备方法 |
| SI26268A (sl) * | 2021-11-18 | 2023-05-31 | Zupet Rok | Postopek za pripravo hidratirane oblike perindopril l-arginina |
| CN114149357B (zh) * | 2021-12-29 | 2024-06-25 | 江苏嘉逸医药有限公司 | 一种γ晶型培哚普利精氨酸盐的制备方法 |
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| US4616031A (en) * | 1979-12-07 | 1986-10-07 | Adir | Perhydroindole-2-carboxylic acids as antihypertensives |
| US4508729A (en) | 1979-12-07 | 1985-04-02 | Adir | Substituted iminodiacids, their preparation and pharmaceutical compositions containing them |
| US4616030A (en) * | 1979-12-07 | 1986-10-07 | Adir | Perhydroindole-2-carboxylic acids as antihypertensives |
| US5162362A (en) * | 1980-08-30 | 1992-11-10 | Hoechst Aktiengesellschaft | Octahydroindole-2-carboxylic acids |
| DE3226768A1 (de) * | 1981-11-05 | 1983-05-26 | Hoechst Ag, 6230 Frankfurt | Derivate der cis, endo-2-azabicyclo-(3.3.0)-octan-3-carbonsaeure, verfahren zu ihrer herstellung, diese enthaltende mittel und deren verwendung |
| FR2620709B1 (fr) | 1987-09-17 | 1990-09-07 | Adir | Procede de synthese industrielle du perindopril et de ses principaux intermediaires de synthese |
| GB9101443D0 (en) | 1991-01-23 | 1991-03-06 | Plessey Telecomm | Coin mechanisms |
| FR2811319B1 (fr) * | 2000-07-06 | 2002-08-23 | Adir | Nouvelle forme cristalline beta du sel de tert-butylamine du perindopril, son procede de preparation et les compositions pharmaceutiques qui la contiennent |
| FR2811318B1 (fr) * | 2000-07-06 | 2002-08-23 | Adir | Nouvelle forme cristalline gamma du sel de tert-butylamine du perindopril, son procede de preparation et les compositions pharmaceutiques qui la contiennent |
| FR2838648B1 (fr) | 2002-04-18 | 2004-05-21 | Servier Lab | Nouveau sel de perindopril et les compositions pharmaceutiques qui le contiennent |
| CA2517205C (en) * | 2003-02-28 | 2010-08-24 | Lupin Limited | Process for preparation of perindopril and salts thereof |
| DE60302287T2 (de) * | 2003-08-29 | 2006-08-10 | Les Laboratoires Servier | Verfahren für die Synthese von Perindopril und seiner pharmazeutisch annehmbaren Salzen |
| PT1420029E (pt) * | 2003-12-10 | 2008-04-14 | Servier Lab | Processo de síntese do perindopril e dos seus sais farmaceuticamente aceitáveis |
| US7615571B2 (en) * | 2004-05-31 | 2009-11-10 | Ipca Laboratories Ltd. | Process for manufacture of pure (2S, 3aS, 7aS)-1-[(2S)-2-[[(1S)-1-(ethoxycarbonyl) butyl]amino]-1-oxopropyl] octahydro-1H-indole-2-carboxylic acid and its tert. butyl amine salt |
| CA2614099A1 (en) * | 2005-07-05 | 2007-01-11 | Cipla Limited | Process for the synthesis of the ace inhibitor |
| FR2897866B1 (fr) * | 2006-02-28 | 2008-04-18 | Servier Lab | Forme cristalline alpha du sel d'arginine du perindopril, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| FR2897865B1 (fr) * | 2006-02-28 | 2008-04-18 | Servier Lab | Forme cristalline beta du sel d'arginine du perindopril, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| EP1864973A1 (en) | 2006-06-09 | 2007-12-12 | Sochinaz SA | Process for the preparation of perindopril and salts thereof |
| DK2318365T3 (da) | 2008-06-24 | 2015-11-23 | Mylan Lab Ltd | Hidtil ukendte polymorfe former af perindopril (l)-arginin og fremgangsmåde til fremstilling heraf |
| AU2009212902A1 (en) | 2008-09-03 | 2010-03-18 | Apotex Pharmachem Inc. | Amorphous form of an L-arginine salt of perindopril and processes of preparation thereof |
| AU2013328352A1 (en) * | 2012-10-10 | 2015-05-14 | Piramal Enterprises Limited | An improved process for preparation of Perindopril intermediate |
-
2009
- 2009-06-22 DK DK09769810.4T patent/DK2318365T3/da active
- 2009-06-22 CA CA2729604A patent/CA2729604C/en not_active Expired - Fee Related
- 2009-06-22 ES ES09769810.4T patent/ES2552653T3/es active Active
- 2009-06-22 EP EP09769810.4A patent/EP2318365B1/en not_active Revoked
- 2009-06-22 WO PCT/IN2009/000357 patent/WO2009157018A2/en active Application Filing
- 2009-06-22 SI SI200931310T patent/SI2318365T1/sl unknown
- 2009-06-22 HU HUE09769810A patent/HUE025982T2/en unknown
- 2009-06-22 PT PT97698104T patent/PT2318365E/pt unknown
- 2009-06-22 AU AU2009263737A patent/AU2009263737B2/en active Active
- 2009-06-22 PL PL09769810T patent/PL2318365T3/pl unknown
- 2009-06-22 CA CA2919564A patent/CA2919564A1/en not_active Abandoned
- 2009-06-22 EP EP13003519.9A patent/EP2682388B1/en not_active Revoked
- 2009-06-22 US US13/001,180 patent/US8686161B2/en not_active Expired - Fee Related
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2014
- 2014-01-23 US US14/161,967 patent/US20140135504A1/en not_active Abandoned
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2015
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- 2015-11-10 CY CY20151101010T patent/CY1116930T1/el unknown
- 2015-11-11 HR HRP20151208TT patent/HRP20151208T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009157018A2 (en) | 2009-12-30 |
| CA2919564A1 (en) | 2009-12-30 |
| CA2729604A1 (en) | 2009-12-30 |
| US20140135504A1 (en) | 2014-05-15 |
| WO2009157018A3 (en) | 2010-07-29 |
| EP2318365B1 (en) | 2015-08-12 |
| EP2682388B1 (en) | 2018-01-10 |
| SI2318365T1 (sl) | 2016-01-29 |
| PT2318365E (pt) | 2015-11-25 |
| HRP20151208T1 (hr) | 2015-12-18 |
| AU2009263737A1 (en) | 2009-12-30 |
| CY1116930T1 (el) | 2017-04-05 |
| EP2318365A2 (en) | 2011-05-11 |
| US20150336890A1 (en) | 2015-11-26 |
| EP2682388A1 (en) | 2014-01-08 |
| CA2729604C (en) | 2017-12-05 |
| WO2009157018A9 (en) | 2010-06-10 |
| PL2318365T3 (pl) | 2016-02-29 |
| US9725412B2 (en) | 2017-08-08 |
| US20110301357A1 (en) | 2011-12-08 |
| AU2009263737B2 (en) | 2013-10-24 |
| HUE025982T2 (en) | 2016-05-30 |
| US8686161B2 (en) | 2014-04-01 |
| ES2552653T3 (es) | 2015-12-01 |
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