NO329903B1 - Syntetiske polysakkarider, farmasoytiske preparater inneholdende slike samt anvendelse derav - Google Patents
Syntetiske polysakkarider, farmasoytiske preparater inneholdende slike samt anvendelse derav Download PDFInfo
- Publication number
- NO329903B1 NO329903B1 NO20003662A NO20003662A NO329903B1 NO 329903 B1 NO329903 B1 NO 329903B1 NO 20003662 A NO20003662 A NO 20003662A NO 20003662 A NO20003662 A NO 20003662A NO 329903 B1 NO329903 B1 NO 329903B1
- Authority
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- Norway
- Prior art keywords
- methyl
- glucopyranosyl
- compound
- tri
- silica gel
- Prior art date
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- 150000004676 glycans Chemical class 0.000 title claims description 28
- 229920001282 polysaccharide Polymers 0.000 title claims description 27
- 239000005017 polysaccharide Substances 0.000 title claims description 27
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 12
- 239000000203 mixture Substances 0.000 claims description 95
- 238000004519 manufacturing process Methods 0.000 claims description 89
- 238000002360 preparation method Methods 0.000 claims description 38
- 239000004480 active ingredient Substances 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 208000035475 disorder Diseases 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 208000005189 Embolism Diseases 0.000 claims description 6
- 208000001435 Thromboembolism Diseases 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- 230000007170 pathology Effects 0.000 claims description 5
- 230000015271 coagulation Effects 0.000 claims description 4
- 238000005345 coagulation Methods 0.000 claims description 4
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
- 238000013171 endarterectomy Methods 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 230000002792 vascular Effects 0.000 claims description 3
- 206010002388 Angina unstable Diseases 0.000 claims description 2
- 206010003658 Atrial Fibrillation Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 206010061216 Infarction Diseases 0.000 claims description 2
- 208000005764 Peripheral Arterial Disease Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 208000007814 Unstable Angina Diseases 0.000 claims description 2
- 238000002399 angioplasty Methods 0.000 claims description 2
- 125000000129 anionic group Chemical group 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 230000004064 dysfunction Effects 0.000 claims description 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
- 238000001631 haemodialysis Methods 0.000 claims description 2
- 230000000322 hemodialysis Effects 0.000 claims description 2
- 230000007574 infarction Effects 0.000 claims description 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 2
- 230000000302 ischemic effect Effects 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 230000002537 thrombolytic effect Effects 0.000 claims description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical class [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 150000003385 sodium Chemical class 0.000 claims 1
- 230000009424 thromboembolic effect Effects 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 240
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 201
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 195
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 141
- 239000000741 silica gel Substances 0.000 description 116
- 229910002027 silica gel Inorganic materials 0.000 description 116
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- 150000001875 compounds Chemical class 0.000 description 79
- 238000004809 thin layer chromatography Methods 0.000 description 77
- 239000000243 solution Substances 0.000 description 74
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 44
- 238000004587 chromatography analysis Methods 0.000 description 44
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- 239000012074 organic phase Substances 0.000 description 31
- 239000012299 nitrogen atmosphere Substances 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- 238000000034 method Methods 0.000 description 24
- 238000003756 stirring Methods 0.000 description 22
- 230000015572 biosynthetic process Effects 0.000 description 21
- 238000003786 synthesis reaction Methods 0.000 description 21
- 235000017557 sodium bicarbonate Nutrition 0.000 description 20
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 238000000746 purification Methods 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- GSCHIGXDTVYEEM-UHFFFAOYSA-N 2-[2-[[3-[6-[[4,5-dihydroxy-3-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxymethyl]-3,4-dihydroxy-5-[3,4,5-trihydroxy-6-[(3,4,5-trihydroxyoxan-2-yl)oxymethyl]oxan-2-yl]oxyoxan-2-yl]oxy-4,5-dihydroxy-6-[4,5,6-trihydroxy-2-(hydroxymethyl)oxan Chemical compound OC1C(O)C(O)C(CO)OC1OC1C(OCC2C(C(O)C(O)C(OC3C(OC(O)C(O)C3O)CO)O2)OC2C(C(O)C(OC3C(C(O)C(O)C(COC4C(C(O)C(O)CO4)O)O3)O)C(COC3C(C(O)C(O)CO3)OC3C(C(O)C(O)C(CO)O3)O)O2)O)OCC(O)C1O GSCHIGXDTVYEEM-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000003146 anticoagulant agent Substances 0.000 description 12
- 238000000605 extraction Methods 0.000 description 12
- 229960002897 heparin Drugs 0.000 description 12
- 229920000669 heparin Polymers 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- 239000000377 silicon dioxide Substances 0.000 description 12
- 150000004044 tetrasaccharides Chemical group 0.000 description 12
- UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical compound OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 description 11
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 11
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
- 239000002808 molecular sieve Substances 0.000 description 11
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 11
- 239000012312 sodium hydride Substances 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- 108090000190 Thrombin Proteins 0.000 description 9
- -1 alkali metal cations Chemical class 0.000 description 9
- 230000002785 anti-thrombosis Effects 0.000 description 9
- 239000002243 precursor Substances 0.000 description 9
- 229960004072 thrombin Drugs 0.000 description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 8
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- 150000002772 monosaccharides Chemical group 0.000 description 7
- 150000002482 oligosaccharides Chemical class 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 229940125898 compound 5 Drugs 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 150000002016 disaccharides Chemical class 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 229920002683 Glycosaminoglycan Polymers 0.000 description 5
- LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 229960002246 beta-d-glucopyranose Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 229920001542 oligosaccharide Polymers 0.000 description 5
- 239000012429 reaction media Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 4
- 108010074860 Factor Xa Proteins 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 102000004211 Platelet factor 4 Human genes 0.000 description 4
- 108090000778 Platelet factor 4 Proteins 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 229930182475 S-glycoside Natural products 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000004133 Sodium thiosulphate Substances 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 239000000370 acceptor Substances 0.000 description 4
- 229940127219 anticoagulant drug Drugs 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 235000015497 potassium bicarbonate Nutrition 0.000 description 4
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 4
- 239000011736 potassium bicarbonate Substances 0.000 description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 4
- 235000019345 sodium thiosulphate Nutrition 0.000 description 4
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 150000003569 thioglycosides Chemical class 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 4
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 3
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 3
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 3
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical class CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 3
- PZUPAGRIHCRVKN-UHFFFAOYSA-N 5-[5-[3,4-dihydroxy-6-[(3,4,5-trihydroxyoxan-2-yl)oxymethyl]-5-[3,4,5-trihydroxy-6-[(3,4,5-trihydroxyoxan-2-yl)oxymethyl]oxan-2-yl]oxyoxan-2-yl]oxy-3,4-dihydroxy-6-[(3,4,5-trihydroxyoxan-2-yl)oxymethyl]oxan-2-yl]oxy-6-(hydroxymethyl)oxane-2,3,4-triol Chemical group OCC1OC(O)C(O)C(O)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(COC4C(C(O)C(O)CO4)O)O3)O)C(COC3C(C(O)C(O)CO3)O)O2)O)C(COC2C(C(O)C(O)CO2)O)O1 PZUPAGRIHCRVKN-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920005654 Sephadex Polymers 0.000 description 3
- 239000012507 Sephadex™ Substances 0.000 description 3
- 239000005708 Sodium hypochlorite Substances 0.000 description 3
- DRUIESSIVFYOMK-UHFFFAOYSA-N Trichloroacetonitrile Chemical compound ClC(Cl)(Cl)C#N DRUIESSIVFYOMK-UHFFFAOYSA-N 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 229960004676 antithrombotic agent Drugs 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000007127 saponification reaction Methods 0.000 description 3
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
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- 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Polymers & Plastics (AREA)
- Materials Engineering (AREA)
- Biochemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9800515A FR2773804B1 (fr) | 1998-01-19 | 1998-01-19 | Polysaccharides de synthese, procede pour leur preparation et compositions pharmaceutiques le contenant |
| PCT/FR1999/000044 WO1999036443A1 (fr) | 1998-01-19 | 1999-01-13 | Polysaccharides de synthese, procede pour leur preparation et compositions pharmaceutiques le contenant |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20003662D0 NO20003662D0 (no) | 2000-07-17 |
| NO20003662L NO20003662L (no) | 2000-09-14 |
| NO329903B1 true NO329903B1 (no) | 2011-01-24 |
Family
ID=9521914
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20003662A NO329903B1 (no) | 1998-01-19 | 2000-07-17 | Syntetiske polysakkarider, farmasoytiske preparater inneholdende slike samt anvendelse derav |
Country Status (41)
| Country | Link |
|---|---|
| US (1) | US6528497B1 (es) |
| EP (1) | EP1049721B1 (es) |
| JP (1) | JP4402835B2 (es) |
| KR (1) | KR100513196B1 (es) |
| CN (1) | CN1165550C (es) |
| AR (1) | AR013019A1 (es) |
| AT (1) | ATE209219T1 (es) |
| AU (1) | AU741748B2 (es) |
| BR (1) | BRPI9907025B8 (es) |
| CA (1) | CA2317465C (es) |
| CO (1) | CO4970795A1 (es) |
| CZ (1) | CZ297815B6 (es) |
| DE (1) | DE69900718T2 (es) |
| DK (1) | DK1049721T3 (es) |
| DZ (1) | DZ2709A1 (es) |
| EE (1) | EE04157B1 (es) |
| EG (1) | EG23982A (es) |
| ES (1) | ES2168000T3 (es) |
| FR (1) | FR2773804B1 (es) |
| GT (1) | GT199900003A (es) |
| HK (1) | HK1030002A1 (es) |
| HR (1) | HRP20000480B1 (es) |
| HU (1) | HU228333B1 (es) |
| IL (1) | IL137241A0 (es) |
| MA (1) | MA26597A1 (es) |
| MY (1) | MY119090A (es) |
| NO (1) | NO329903B1 (es) |
| NZ (1) | NZ505492A (es) |
| PE (1) | PE20000269A1 (es) |
| PL (1) | PL202802B1 (es) |
| PT (1) | PT1049721E (es) |
| RU (1) | RU2211224C2 (es) |
| SA (1) | SA99191113B1 (es) |
| SI (1) | SI1049721T1 (es) |
| SK (1) | SK283411B6 (es) |
| TR (1) | TR200002078T2 (es) |
| TW (1) | TW548279B (es) |
| UA (1) | UA60352C2 (es) |
| UY (1) | UY25356A1 (es) |
| WO (1) | WO1999036443A1 (es) |
| ZA (1) | ZA99355B (es) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2814463B1 (fr) | 2000-09-22 | 2002-11-15 | Sanofi Synthelabo | Nouveaux polysaccharides a activite antithrombotique comprenant au moins une liaison covalente avec la biotine ou un derive de la biotine |
| FR2874924B1 (fr) | 2004-09-09 | 2006-12-01 | Sanofi Aventis Sa | Hexadecasaccharides biotinyles, leur preparation et leur utilisation therapeutique |
| TWI403334B (zh) * | 2004-12-23 | 2013-08-01 | Merck Sharp & Dohme | 包含生物素殘基之抗血栓雙重抑制劑 |
| GB0507577D0 (en) | 2005-04-14 | 2005-05-18 | Novartis Ag | Organic compounds |
| IL188647A0 (en) * | 2008-01-08 | 2008-11-03 | Orina Gribova | Adaptable structured drug and supplements administration system (for oral and/or transdermal applications) |
| WO2009130704A1 (en) * | 2008-04-24 | 2009-10-29 | Technion Research And Development Foundation Ltd. | Beta-lactoglobulin-polysaccharide nanoparticles for hydrophobic bioactive compounds |
| US8614314B2 (en) | 2008-05-30 | 2013-12-24 | Momenta Pharmaceuticals, Inc. | Saccharide structures and methods of making and using such structures |
| FR2935386B1 (fr) * | 2008-08-26 | 2010-09-10 | Sanofi Aventis | Nouveaux polysaccharides a activite antithrombotique comprenant une liaion covalente avec une chaine amine |
| WO2010117803A2 (en) * | 2009-03-30 | 2010-10-14 | University Of Georgia Research Foundation, Inc. | Heparan sulfate synthesis |
| BR112012000379A2 (pt) | 2009-07-09 | 2016-03-29 | Oshadi Drug Administration Ltd | composições de matriz carreadora, métodos e usos |
| WO2011014793A2 (en) | 2009-07-31 | 2011-02-03 | Reliable Biopharmaceutical Corporation | Process for preparing fondaparinux sodium and intermediates useful in the synthesis thereof |
| FR2949115B1 (fr) | 2009-08-14 | 2012-11-02 | Sanofi Aventis | OLIGOSACCHARIDES N-SULFATES ACTIVATEURS DES RECEPTEURS DES FGFs, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE |
| FR2949114B1 (fr) | 2009-08-14 | 2011-08-26 | Sanofi Aventis | OCTASACCHARIDES N-ACYLES ACTIVATEURS DES RECEPTEURS DES FGFs, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE |
| US8420790B2 (en) | 2009-10-30 | 2013-04-16 | Reliable Biopharmaceutical Corporation | Efficient and scalable process for the manufacture of Fondaparinux sodium |
| EP2614089A1 (fr) | 2010-09-10 | 2013-07-17 | Sanofi-Aventis | Polysaccharides biotinyles a activite antithrombotique et presentant une stabilite metabolique amelioree |
| US9005664B2 (en) | 2010-10-17 | 2015-04-14 | Technion Research And Development Foundation Ltd. | Denatured lactoglobulin and polyphenol coassemblies |
| FR2970969B1 (fr) | 2011-01-27 | 2013-10-18 | Sanofi Aventis | Oligosaccharides 3-o-alkyles activateurs des recepteurs des fgfs, leur preparation et leur application en therapeutique |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ260933A (en) * | 1993-07-16 | 1996-07-26 | Hercules Inc | Cation-complexed polysaccharides; use in foods and pharmaceuticals |
| FR2749849B1 (fr) * | 1996-06-14 | 1998-09-04 | Sanofi Sa | Polysaccharides synthetiques, procede pour leur preparation et compositions pharmaceutiques les contenant |
| CZ427499A3 (cs) * | 1998-05-29 | 2000-05-17 | The Procter & Gamble Company | Jemné topické antimikrobiální přípravky |
-
1998
- 1998-01-19 FR FR9800515A patent/FR2773804B1/fr not_active Expired - Lifetime
-
1999
- 1999-01-13 NZ NZ505492A patent/NZ505492A/en not_active IP Right Cessation
- 1999-01-13 WO PCT/FR1999/000044 patent/WO1999036443A1/fr active IP Right Grant
- 1999-01-13 TR TR2000/02078T patent/TR200002078T2/xx unknown
- 1999-01-13 HU HU0102009A patent/HU228333B1/hu not_active IP Right Cessation
- 1999-01-13 RU RU2000119753/04A patent/RU2211224C2/ru not_active IP Right Cessation
- 1999-01-13 PL PL341875A patent/PL202802B1/pl unknown
- 1999-01-13 CN CNB998022438A patent/CN1165550C/zh not_active Expired - Fee Related
- 1999-01-13 KR KR10-2000-7007824A patent/KR100513196B1/ko not_active IP Right Cessation
- 1999-01-13 UA UA2000074011A patent/UA60352C2/uk unknown
- 1999-01-13 CZ CZ20002635A patent/CZ297815B6/cs not_active IP Right Cessation
- 1999-01-13 EP EP99900524A patent/EP1049721B1/fr not_active Expired - Lifetime
- 1999-01-13 DK DK99900524T patent/DK1049721T3/da active
- 1999-01-13 BR BRPI9907025A patent/BRPI9907025B8/pt not_active IP Right Cessation
- 1999-01-13 IL IL13724199A patent/IL137241A0/xx not_active IP Right Cessation
- 1999-01-13 DE DE69900718T patent/DE69900718T2/de not_active Expired - Lifetime
- 1999-01-13 PT PT99900524T patent/PT1049721E/pt unknown
- 1999-01-13 CA CA002317465A patent/CA2317465C/en not_active Expired - Fee Related
- 1999-01-13 ES ES99900524T patent/ES2168000T3/es not_active Expired - Lifetime
- 1999-01-13 EE EEP200000429A patent/EE04157B1/xx unknown
- 1999-01-13 SK SK1078-2000A patent/SK283411B6/sk not_active IP Right Cessation
- 1999-01-13 US US09/600,506 patent/US6528497B1/en not_active Expired - Lifetime
- 1999-01-13 AT AT99900524T patent/ATE209219T1/de active
- 1999-01-13 AU AU19745/99A patent/AU741748B2/en not_active Ceased
- 1999-01-13 SI SI9930025T patent/SI1049721T1/xx unknown
- 1999-01-13 JP JP2000540158A patent/JP4402835B2/ja not_active Expired - Fee Related
- 1999-01-14 GT GT199900003A patent/GT199900003A/es unknown
- 1999-01-15 MA MA25431A patent/MA26597A1/fr unknown
- 1999-01-16 DZ DZ990010A patent/DZ2709A1/xx active
- 1999-01-16 EG EG5499A patent/EG23982A/xx active
- 1999-01-18 UY UY25356A patent/UY25356A1/es not_active Application Discontinuation
- 1999-01-18 TW TW088100716A patent/TW548279B/zh not_active IP Right Cessation
- 1999-01-18 MY MYPI99000203A patent/MY119090A/en unknown
- 1999-01-18 AR ARP990100172A patent/AR013019A1/es active IP Right Grant
- 1999-01-19 PE PE1999000044A patent/PE20000269A1/es not_active Application Discontinuation
- 1999-01-19 ZA ZA9900355A patent/ZA99355B/xx unknown
- 1999-01-19 CO CO99002526A patent/CO4970795A1/es unknown
- 1999-02-27 SA SA99191113A patent/SA99191113B1/ar unknown
-
2000
- 2000-07-17 NO NO20003662A patent/NO329903B1/no not_active IP Right Cessation
- 2000-07-19 HR HR970630A patent/HRP20000480B1/xx not_active IP Right Cessation
-
2001
- 2001-02-12 HK HK01101003A patent/HK1030002A1/xx not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |