ZA200109944B - A substantially crystalline form of melagatran. - Google Patents
A substantially crystalline form of melagatran. Download PDFInfo
- Publication number
- ZA200109944B ZA200109944B ZA200109944A ZA200109944A ZA200109944B ZA 200109944 B ZA200109944 B ZA 200109944B ZA 200109944 A ZA200109944 A ZA 200109944A ZA 200109944 A ZA200109944 A ZA 200109944A ZA 200109944 B ZA200109944 B ZA 200109944B
- Authority
- ZA
- South Africa
- Prior art keywords
- compound
- melagatran
- water
- solvent
- iso
- Prior art date
Links
- DKWNMCUOEDMMIN-PKOBYXMFSA-N melagatran Chemical compound C1=CC(C(=N)N)=CC=C1CNC(=O)[C@H]1N(C(=O)[C@H](NCC(O)=O)C2CCCCC2)CC1 DKWNMCUOEDMMIN-PKOBYXMFSA-N 0.000 title claims description 61
- 229960002137 melagatran Drugs 0.000 title claims description 61
- 150000001875 compounds Chemical class 0.000 claims description 99
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 91
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 67
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 61
- 238000000034 method Methods 0.000 claims description 46
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 44
- 239000002904 solvent Substances 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 34
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 30
- 230000008569 process Effects 0.000 claims description 30
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 229960004592 isopropanol Drugs 0.000 claims description 22
- 239000000126 substance Substances 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 125000005233 alkylalcohol group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 10
- -1 alkyl acetates Chemical class 0.000 claims description 8
- 238000001938 differential scanning calorimetry curve Methods 0.000 claims description 8
- 238000009472 formulation Methods 0.000 claims description 8
- 108090000190 Thrombin Proteins 0.000 claims description 6
- 239000012296 anti-solvent Substances 0.000 claims description 6
- 229960004072 thrombin Drugs 0.000 claims description 6
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 5
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 229940043265 methyl isobutyl ketone Drugs 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 4
- 239000012298 atmosphere Substances 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 4
- OGHBATFHNDZKSO-UHFFFAOYSA-N propan-2-olate Chemical compound CC(C)[O-] OGHBATFHNDZKSO-UHFFFAOYSA-N 0.000 claims description 4
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 claims description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 3
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 claims description 3
- 230000001747 exhibiting effect Effects 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 150000001983 dialkylethers Chemical class 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 4
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 125000001931 aliphatic group Chemical group 0.000 claims 1
- 150000005215 alkyl ethers Chemical class 0.000 claims 1
- 238000010009 beating Methods 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 239000000243 solution Substances 0.000 description 51
- 239000013078 crystal Substances 0.000 description 32
- 238000002425 crystallisation Methods 0.000 description 29
- 235000019441 ethanol Nutrition 0.000 description 20
- 229960004756 ethanol Drugs 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 150000004682 monohydrates Chemical class 0.000 description 17
- 239000012453 solvate Substances 0.000 description 17
- 238000003109 Karl Fischer titration Methods 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 238000000113 differential scanning calorimetry Methods 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000003960 organic solvent Substances 0.000 description 10
- 239000002002 slurry Substances 0.000 description 10
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 229940079593 drug Drugs 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 238000002411 thermogravimetry Methods 0.000 description 8
- 238000001035 drying Methods 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 238000003860 storage Methods 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- RWIOMIFNKVTIAA-JUOYHRLASA-N 2-[[(1r)-2-[(2s)-2-[(4-carbamimidoylphenyl)methylcarbamoyl]azetidin-1-yl]-1-cyclohexyl-2-oxoethyl]amino]acetic acid;hydrate Chemical compound O.C1=CC(C(=N)N)=CC=C1CNC(=O)[C@H]1N(C(=O)[C@H](NCC(O)=O)C2CCCCC2)CC1 RWIOMIFNKVTIAA-JUOYHRLASA-N 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 230000018044 dehydration Effects 0.000 description 5
- 238000006297 dehydration reaction Methods 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 150000004677 hydrates Chemical class 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000008399 tap water Substances 0.000 description 4
- 235000020679 tap water Nutrition 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000002050 diffraction method Methods 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000036571 hydration Effects 0.000 description 3
- 238000006703 hydration reaction Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- IADUEWIQBXOCDZ-VKHMYHEASA-N (S)-azetidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 238000012369 In process control Methods 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- JHVLLYQQQYIWKX-UHFFFAOYSA-N benzyl 2-bromoacetate Chemical compound BrCC(=O)OCC1=CC=CC=C1 JHVLLYQQQYIWKX-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000002144 chemical decomposition reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 229940088679 drug related substance Drugs 0.000 description 2
- 238000010965 in-process control Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- KKQZWTDAJBOBSS-UHFFFAOYSA-N n'-(aminomethyl)benzenecarboximidamide Chemical compound NCNC(=N)C1=CC=CC=C1 KKQZWTDAJBOBSS-UHFFFAOYSA-N 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- WAMWSIDTKSNDCU-ZETCQYMHSA-N (2s)-2-azaniumyl-2-cyclohexylacetate Chemical compound OC(=O)[C@@H](N)C1CCCCC1 WAMWSIDTKSNDCU-ZETCQYMHSA-N 0.000 description 1
- OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 238000007707 calorimetry Methods 0.000 description 1
- JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003517 fume Substances 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940032007 methylethyl ketone Drugs 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000011085 pressure filtration Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012066 reaction slurry Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Liquid Crystal Substances (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9902550A SE9902550D0 (sv) | 1999-07-02 | 1999-07-02 | New crystalline forms |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200109944B true ZA200109944B (en) | 2003-03-03 |
Family
ID=20416364
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200109944A ZA200109944B (en) | 1999-07-02 | 2001-12-03 | A substantially crystalline form of melagatran. |
Country Status (33)
| Country | Link |
|---|---|
| US (1) | US6479078B1 (sk) |
| EP (1) | EP1196431B1 (sk) |
| JP (1) | JP2003503508A (sk) |
| KR (1) | KR20020020765A (sk) |
| CN (1) | CN100537598C (sk) |
| AR (1) | AR035553A1 (sk) |
| AT (1) | ATE339438T1 (sk) |
| AU (1) | AU765614B2 (sk) |
| BR (1) | BR0012035A (sk) |
| CA (1) | CA2376944A1 (sk) |
| CY (1) | CY1107542T1 (sk) |
| CZ (1) | CZ20014722A3 (sk) |
| DE (1) | DE60030723T2 (sk) |
| DK (1) | DK1196431T3 (sk) |
| EE (1) | EE200100646A (sk) |
| ES (1) | ES2270849T3 (sk) |
| HK (1) | HK1045529B (sk) |
| HU (1) | HUP0202322A3 (sk) |
| IL (1) | IL146972A0 (sk) |
| IS (1) | IS6215A (sk) |
| MX (1) | MXPA01013441A (sk) |
| MY (1) | MY122760A (sk) |
| NO (1) | NO20016419L (sk) |
| NZ (1) | NZ516187A (sk) |
| PL (1) | PL352872A1 (sk) |
| PT (1) | PT1196431E (sk) |
| RU (1) | RU2243973C2 (sk) |
| SE (1) | SE9902550D0 (sk) |
| SK (1) | SK18832001A3 (sk) |
| TR (1) | TR200103855T2 (sk) |
| TW (1) | TWI250991B (sk) |
| WO (1) | WO2001002426A1 (sk) |
| ZA (1) | ZA200109944B (sk) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6976012B1 (en) | 2000-01-24 | 2005-12-13 | Sony Corporation | Method and apparatus of using a neural network to train a neural network |
| AR035216A1 (es) * | 2000-12-01 | 2004-05-05 | Astrazeneca Ab | Derivados de acido mandelico ,derivados farmaceuticamente aceptables, uso de estos derivados para la fabricacion de medicamentos, metodos de tratamiento ,procesos para la preparacion de estos derivados, y compuestos intermediarios |
| US7129233B2 (en) * | 2000-12-01 | 2006-10-31 | Astrazeneca Ab | Mandelic acid derivatives and their use as thrombin inhibitors |
| AR034517A1 (es) * | 2001-06-21 | 2004-02-25 | Astrazeneca Ab | Formulacion farmaceutica |
| SE0201659D0 (sv) * | 2002-05-31 | 2002-05-31 | Astrazeneca Ab | Modified release pharmaceutical formulation |
| SE0201661D0 (sv) * | 2002-05-31 | 2002-05-31 | Astrazeneca Ab | New salts |
| US7781424B2 (en) * | 2003-05-27 | 2010-08-24 | Astrazeneca Ab | Modified release pharmaceutical formulation |
| CA2547625C (en) * | 2003-11-27 | 2012-07-24 | Ajinomoto Co., Inc. | Crystals of phenylalanine derivatives and production methods thereof |
| US20050209211A1 (en) * | 2004-03-16 | 2005-09-22 | Devalina Law | Trihemihydrate, anhydrate and novel hydrate forms of Cefdinir |
| US7524354B2 (en) * | 2005-07-07 | 2009-04-28 | Research Foundation Of State University Of New York | Controlled synthesis of highly monodispersed gold nanoparticles |
| TW200827336A (en) * | 2006-12-06 | 2008-07-01 | Astrazeneca Ab | New crystalline forms |
| US20090061000A1 (en) * | 2007-08-31 | 2009-03-05 | Astrazeneca Ab | Pharmaceutical formulation use 030 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0687881A (ja) * | 1992-09-07 | 1994-03-29 | Asahi Chem Ind Co Ltd | ロキタマイシン・一水和物結晶、及びその製造法 |
| JP3077925B2 (ja) * | 1992-12-15 | 2000-08-21 | ヤマサ醤油株式会社 | ２’−デオキシ−２’−メチリデンシチジン無水物結晶およびその製造法 |
| SE9301916D0 (sv) | 1993-06-03 | 1993-06-03 | Ab Astra | New peptides derivatives |
| SE9404196D0 (sv) * | 1994-12-02 | 1994-12-02 | Astra Ab | New antithrombotic formulation |
| JP3182685B2 (ja) * | 1995-09-01 | 2001-07-03 | 北陸製薬株式会社 | 水和物結晶及びその製造方法 |
| JP2914324B2 (ja) * | 1995-10-23 | 1999-06-28 | 味の素株式会社 | ピペリジン誘導体の結晶並びにその製造中間体及び製造方法 |
| TW541316B (en) * | 1995-12-21 | 2003-07-11 | Astrazeneca Ab | Prodrugs of thrombin inhibitors |
| SE9603724D0 (sv) * | 1996-10-11 | 1996-10-11 | Astra Ab | New pharmaceutical parenteral formulation of a thrombin inhibitor |
| SE9802974D0 (sv) | 1998-09-03 | 1998-09-03 | Astra Ab | New crystalline forms |
| FR2793418B1 (fr) * | 1999-05-11 | 2001-07-27 | Synthelabo | Formulations galeniques d'agents antithrombotiques pour administration sous-cutanee |
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1999
- 1999-07-02 SE SE9902550A patent/SE9902550D0/xx unknown
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2000
- 2000-06-27 TW TW089112623A patent/TWI250991B/zh not_active IP Right Cessation
- 2000-06-30 IL IL14697200A patent/IL146972A0/xx unknown
- 2000-06-30 PL PL00352872A patent/PL352872A1/xx not_active Application Discontinuation
- 2000-06-30 SK SK1883-2001A patent/SK18832001A3/sk unknown
- 2000-06-30 KR KR1020017016964A patent/KR20020020765A/ko not_active Application Discontinuation
- 2000-06-30 PT PT00946687T patent/PT1196431E/pt unknown
- 2000-06-30 CA CA002376944A patent/CA2376944A1/en not_active Abandoned
- 2000-06-30 AT AT00946687T patent/ATE339438T1/de not_active IP Right Cessation
- 2000-06-30 MY MYPI20003011 patent/MY122760A/en unknown
- 2000-06-30 ES ES00946687T patent/ES2270849T3/es not_active Expired - Lifetime
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- 2000-06-30 EE EEP200100646A patent/EE200100646A/xx unknown
- 2000-06-30 EP EP00946687A patent/EP1196431B1/en not_active Expired - Lifetime
- 2000-06-30 AR ARP000103347A patent/AR035553A1/es unknown
- 2000-06-30 RU RU2001134299/04A patent/RU2243973C2/ru not_active IP Right Cessation
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- 2000-06-30 NZ NZ516187A patent/NZ516187A/en not_active IP Right Cessation
- 2000-06-30 AU AU60408/00A patent/AU765614B2/en not_active Ceased
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- 2000-06-30 BR BR0012035-9A patent/BR0012035A/pt not_active IP Right Cessation
- 2000-06-30 DK DK00946687T patent/DK1196431T3/da active
- 2000-06-30 MX MXPA01013441A patent/MXPA01013441A/es active IP Right Grant
- 2000-06-30 WO PCT/SE2000/001398 patent/WO2001002426A1/en active IP Right Grant
- 2000-06-30 JP JP2001507862A patent/JP2003503508A/ja active Pending
- 2000-06-30 CN CNB008096902A patent/CN100537598C/zh not_active Expired - Fee Related
- 2000-06-30 US US09/623,165 patent/US6479078B1/en not_active Expired - Fee Related
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2001
- 2001-12-03 ZA ZA200109944A patent/ZA200109944B/en unknown
- 2001-12-27 IS IS6215A patent/IS6215A/is unknown
- 2001-12-28 NO NO20016419A patent/NO20016419L/no not_active Application Discontinuation
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2002
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2006
- 2006-12-12 CY CY20061101785T patent/CY1107542T1/el unknown
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