AU2004262584A1 - Polysaccharides derivatives with high antithrombotic activity in plasma - Google Patents
Polysaccharides derivatives with high antithrombotic activity in plasma Download PDFInfo
- Publication number
- AU2004262584A1 AU2004262584A1 AU2004262584A AU2004262584A AU2004262584A1 AU 2004262584 A1 AU2004262584 A1 AU 2004262584A1 AU 2004262584 A AU2004262584 A AU 2004262584A AU 2004262584 A AU2004262584 A AU 2004262584A AU 2004262584 A1 AU2004262584 A1 AU 2004262584A1
- Authority
- AU
- Australia
- Prior art keywords
- sulphation
- process according
- partial
- acetyl
- acetyl heparosan
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 229920001282 polysaccharide Polymers 0.000 title claims abstract description 76
- 239000005017 polysaccharide Substances 0.000 title claims abstract description 76
- 150000004676 glycans Chemical class 0.000 title claims abstract description 75
- 230000002785 anti-thrombosis Effects 0.000 title claims description 15
- 238000000034 method Methods 0.000 claims abstract description 140
- 230000008569 process Effects 0.000 claims abstract description 89
- 230000000694 effects Effects 0.000 claims abstract description 74
- 230000036961 partial effect Effects 0.000 claims abstract description 72
- 238000002360 preparation method Methods 0.000 claims abstract description 39
- 238000006345 epimerization reaction Methods 0.000 claims abstract description 28
- 102000004190 Enzymes Human genes 0.000 claims abstract description 27
- 108090000790 Enzymes Proteins 0.000 claims abstract description 27
- 238000003381 deacetylation reaction Methods 0.000 claims abstract description 15
- 241000588724 Escherichia coli Species 0.000 claims abstract description 12
- 230000002255 enzymatic effect Effects 0.000 claims abstract description 12
- 230000001580 bacterial effect Effects 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims abstract description 10
- 229920002683 Glycosaminoglycan Polymers 0.000 claims abstract description 9
- 239000003085 diluting agent Substances 0.000 claims abstract description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 3
- 229960002897 heparin Drugs 0.000 claims description 84
- 229920000669 heparin Polymers 0.000 claims description 84
- 239000003795 chemical substances by application Substances 0.000 claims description 40
- 125000003047 N-acetyl group Chemical group 0.000 claims description 35
- 239000011347 resin Substances 0.000 claims description 30
- 229920005989 resin Polymers 0.000 claims description 30
- 238000001228 spectrum Methods 0.000 claims description 29
- 238000011282 treatment Methods 0.000 claims description 28
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 claims description 27
- 229940088598 enzyme Drugs 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
- 239000003146 anticoagulant agent Substances 0.000 claims description 21
- 239000000872 buffer Substances 0.000 claims description 21
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 108090000190 Thrombin Proteins 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 229960004072 thrombin Drugs 0.000 claims description 14
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 claims description 13
- JNYAEWCLZODPBN-KVTDHHQDSA-N (2r,3r,4r)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@@H](O)[C@H]1O JNYAEWCLZODPBN-KVTDHHQDSA-N 0.000 claims description 12
- 102100030951 Tissue factor pathway inhibitor Human genes 0.000 claims description 12
- 108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 claims description 12
- 108010022901 Heparin Lyase Proteins 0.000 claims description 11
- 230000005764 inhibitory process Effects 0.000 claims description 11
- 230000014508 negative regulation of coagulation Effects 0.000 claims description 11
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 10
- 239000004019 antithrombin Substances 0.000 claims description 10
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 claims description 9
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 claims description 9
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 claims description 9
- 108091005804 Peptidases Proteins 0.000 claims description 9
- 239000004365 Protease Substances 0.000 claims description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 9
- 239000007995 HEPES buffer Substances 0.000 claims description 8
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 8
- 238000009739 binding Methods 0.000 claims description 8
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 8
- 229960002442 glucosamine Drugs 0.000 claims description 8
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 230000001180 sulfating effect Effects 0.000 claims description 8
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 7
- 239000002798 polar solvent Substances 0.000 claims description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 claims description 6
- 108010074860 Factor Xa Proteins 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- 238000011321 prophylaxis Methods 0.000 claims description 6
- 206010002388 Angina unstable Diseases 0.000 claims description 5
- 206010010356 Congenital anomaly Diseases 0.000 claims description 5
- 208000007814 Unstable Angina Diseases 0.000 claims description 5
- 150000007513 acids Chemical class 0.000 claims description 5
- 230000004913 activation Effects 0.000 claims description 5
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 5
- 230000000302 ischemic effect Effects 0.000 claims description 5
- 230000002107 myocardial effect Effects 0.000 claims description 4
- 208000010125 myocardial infarction Diseases 0.000 claims description 4
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical group [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 claims description 4
- 206010051055 Deep vein thrombosis Diseases 0.000 claims description 3
- 208000005189 Embolism Diseases 0.000 claims description 3
- 241000238631 Hexapoda Species 0.000 claims description 3
- 102000035195 Peptidases Human genes 0.000 claims description 3
- 206010040047 Sepsis Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 206010047249 Venous thrombosis Diseases 0.000 claims description 3
- 230000002744 anti-aggregatory effect Effects 0.000 claims description 3
- 208000009190 disseminated intravascular coagulation Diseases 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 210000004072 lung Anatomy 0.000 claims description 3
- 238000000053 physical method Methods 0.000 claims description 3
- 230000000019 pro-fibrinolytic effect Effects 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims description 2
- 238000003314 affinity selection Methods 0.000 claims description 2
- 238000007068 beta-elimination reaction Methods 0.000 claims description 2
- 239000012634 fragment Substances 0.000 claims description 2
- 235000010344 sodium nitrate Nutrition 0.000 claims description 2
- 239000004317 sodium nitrate Substances 0.000 claims description 2
- 210000005253 yeast cell Anatomy 0.000 claims description 2
- 230000005526 G1 to G0 transition Effects 0.000 claims 2
- 239000000010 aprotic solvent Substances 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 206010003210 Arteriosclerosis Diseases 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 208000011775 arteriosclerosis disease Diseases 0.000 claims 1
- 230000005251 gamma ray Effects 0.000 claims 1
- GQPLMRYTRLFLPF-UHFFFAOYSA-N nitrous oxide Inorganic materials [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 claims 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 claims 1
- 230000000144 pharmacologic effect Effects 0.000 claims 1
- 239000008363 phosphate buffer Substances 0.000 claims 1
- 230000001858 anti-Xa Effects 0.000 abstract description 34
- 239000000047 product Substances 0.000 description 122
- 239000000243 solution Substances 0.000 description 72
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
- 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 32
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 27
- 239000000543 intermediate Substances 0.000 description 23
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 22
- 238000004519 manufacturing process Methods 0.000 description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
- 239000000758 substrate Substances 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 14
- 102000004211 Platelet factor 4 Human genes 0.000 description 14
- 108090000778 Platelet factor 4 Proteins 0.000 description 14
- 239000012528 membrane Substances 0.000 description 14
- 235000010288 sodium nitrite Nutrition 0.000 description 13
- 102000004879 Racemases and epimerases Human genes 0.000 description 12
- 108090001066 Racemases and epimerases Proteins 0.000 description 12
- 238000001556 precipitation Methods 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 230000004071 biological effect Effects 0.000 description 10
- 239000008367 deionised water Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 229940127219 anticoagulant drug Drugs 0.000 description 9
- 238000011026 diafiltration Methods 0.000 description 9
- 239000012467 final product Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 238000000855 fermentation Methods 0.000 description 8
- 230000004151 fermentation Effects 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- IAJILQKETJEXLJ-LECHCGJUSA-N iduronic acid Chemical compound O=C[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-LECHCGJUSA-N 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 108010093096 Immobilized Enzymes Proteins 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- 150000002337 glycosamines Chemical class 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000012916 structural analysis Methods 0.000 description 7
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 6
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 125000002091 cationic group Chemical group 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 235000010469 Glycine max Nutrition 0.000 description 4
- 229920002684 Sepharose Polymers 0.000 description 4
- 150000003863 ammonium salts Chemical class 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000015271 coagulation Effects 0.000 description 4
- 238000005345 coagulation Methods 0.000 description 4
- 230000004907 flux Effects 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 229940097043 glucuronic acid Drugs 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- WKFQMDFSDQFAIC-UHFFFAOYSA-N 2,4-dimethylthiolane 1,1-dioxide Chemical compound CC1CC(C)S(=O)(=O)C1 WKFQMDFSDQFAIC-UHFFFAOYSA-N 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- -1 N-acetyl polysaccharide Chemical class 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000001110 calcium chloride Substances 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 235000011148 calcium chloride Nutrition 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 230000023597 hemostasis Effects 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000012466 permeate Substances 0.000 description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide pyridine complex Chemical class O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 3
- 229910021653 sulphate ion Inorganic materials 0.000 description 3
- 238000000108 ultra-filtration Methods 0.000 description 3
- WFIYPADYPQQLNN-UHFFFAOYSA-N 2-[2-(4-bromopyrazol-1-yl)ethyl]isoindole-1,3-dione Chemical compound C1=C(Br)C=NN1CCN1C(=O)C2=CC=CC=C2C1=O WFIYPADYPQQLNN-UHFFFAOYSA-N 0.000 description 2
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 241000228212 Aspergillus Species 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 108010049003 Fibrinogen Proteins 0.000 description 2
- 102000008946 Fibrinogen Human genes 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Chemical group CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Chemical group CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 2
- 241000320412 Ogataea angusta Species 0.000 description 2
- 241001452677 Ogataea methanolica Species 0.000 description 2
- 241000606856 Pasteurella multocida Species 0.000 description 2
- 108010094028 Prothrombin Proteins 0.000 description 2
- 241000235070 Saccharomyces Species 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical group O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000003544 deproteinization Effects 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940012952 fibrinogen Drugs 0.000 description 2
- 235000013312 flour Nutrition 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 239000003055 low molecular weight heparin Substances 0.000 description 2
- 229940127215 low-molecular weight heparin Drugs 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- AJFDBNQQDYLMJN-UHFFFAOYSA-N n,n-diethylacetamide Chemical compound CCN(CC)C(C)=O AJFDBNQQDYLMJN-UHFFFAOYSA-N 0.000 description 2
- 229950006780 n-acetylglucosamine Drugs 0.000 description 2
- 101150009274 nhr-1 gene Proteins 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- KQJTXYQXRHCWKW-PJSBSAQXSA-N (4s)-4-[[(2s,3s)-2-benzamido-3-methylpentanoyl]amino]-5-[[2-[[(2s)-5-(diaminomethylideneamino)-1-(4-nitroanilino)-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid;hydrochloride Chemical compound Cl.N([C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCCN=C(N)N)C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)C(=O)C1=CC=CC=C1 KQJTXYQXRHCWKW-PJSBSAQXSA-N 0.000 description 1
- CFWRDBDJAOHXSH-SECBINFHSA-N 2-azaniumylethyl [(2r)-2,3-diacetyloxypropyl] phosphate Chemical compound CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OCCN CFWRDBDJAOHXSH-SECBINFHSA-N 0.000 description 1
- 238000005084 2D-nuclear magnetic resonance Methods 0.000 description 1
- CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 229910000906 Bronze Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 241001522878 Escherichia coli B Species 0.000 description 1
- 108010014173 Factor X Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 108010054964 H-hexahydrotyrosyl-alanyl-arginine-4-nitroanilide Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- 239000008118 PEG 6000 Substances 0.000 description 1
- 241000606860 Pasteurella Species 0.000 description 1
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 230000003024 amidolytic effect Effects 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 239000001166 ammonium sulphate Substances 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000001557 animal structure Anatomy 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940127090 anticoagulant agent Drugs 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 238000010420 art technique Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 108010031969 benzoyl-Ile-Glu-Gly-Arg-p-nitroanilide Proteins 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000010974 bronze Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000005626 carbonium group Chemical group 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- KUNSUQLRTQLHQQ-UHFFFAOYSA-N copper tin Chemical compound [Cu].[Sn] KUNSUQLRTQLHQQ-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 150000002016 disaccharides Chemical group 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 230000009144 enzymatic modification Effects 0.000 description 1
- 150000003948 formamides Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 230000001371 heparinic effect Effects 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000002715 modification method Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- VQTGUFBGYOIUFS-UHFFFAOYSA-N nitrosylsulfuric acid Chemical compound OS(=O)(=O)ON=O VQTGUFBGYOIUFS-UHFFFAOYSA-N 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229940051027 pasteurella multocida Drugs 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000012898 sample dilution Substances 0.000 description 1
- 239000013017 sartobind Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- GLVMEDFRYAYDNX-UHFFFAOYSA-M sodium;propan-2-one;chloride Chemical compound [Na+].[Cl-].CC(C)=O GLVMEDFRYAYDNX-UHFFFAOYSA-M 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
Classifications
-
- 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
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- 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
-
- 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
-
- 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
- C08B37/0075—Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/8215—Microorganisms
- Y10S435/822—Microorganisms using bacteria or actinomycetales
- Y10S435/848—Escherichia
- Y10S435/849—Escherichia coli
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Materials Engineering (AREA)
- Polymers & Plastics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT001618A ITMI20031618A1 (it) | 2003-08-06 | 2003-08-06 | Derivati polisaccaridici dotati di alta attivita' |
| ITMI2003A001618 | 2003-08-06 | ||
| PCT/EP2004/051391 WO2005014656A1 (en) | 2003-08-06 | 2004-07-07 | Polysaccharides derivatives with high antithrombotic activity in plasma |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2004262584A1 true AU2004262584A1 (en) | 2005-02-17 |
Family
ID=34131211
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2004262584A Abandoned AU2004262584A1 (en) | 2003-08-06 | 2004-07-07 | Polysaccharides derivatives with high antithrombotic activity in plasma |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US7687249B2 (enExample) |
| EP (1) | EP1654288B9 (enExample) |
| JP (1) | JP2007501305A (enExample) |
| KR (1) | KR20060063933A (enExample) |
| CN (1) | CN1832966A (enExample) |
| AT (1) | ATE458009T1 (enExample) |
| AU (1) | AU2004262584A1 (enExample) |
| BR (1) | BRPI0413346A (enExample) |
| CA (1) | CA2534709A1 (enExample) |
| DE (1) | DE602004025583D1 (enExample) |
| DK (1) | DK1654288T3 (enExample) |
| ES (1) | ES2341249T3 (enExample) |
| IL (1) | IL173482A0 (enExample) |
| IT (1) | ITMI20031618A1 (enExample) |
| MX (1) | MXPA06001511A (enExample) |
| RU (1) | RU2361881C2 (enExample) |
| WO (1) | WO2005014656A1 (enExample) |
| ZA (1) | ZA200601643B (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2006316039B2 (en) * | 2005-11-21 | 2011-08-18 | Ge Healthcare Bio-Sciences Ab | A method of chromatography using semi-synthetic heparin ligands |
| GB0818255D0 (en) | 2008-10-06 | 2008-11-12 | Agency Science Tech & Res | Isolation and identification of glycosaminoglycans |
| US9498494B2 (en) | 2008-09-11 | 2016-11-22 | Agency For Science, Technology And Research | Glycosaminoglycans |
| CN101698838B (zh) * | 2008-12-26 | 2012-05-23 | 北京大学 | 尿苷二磷酸葡萄糖醛酸异构酶及其编码基因与应用 |
| ITMI20091445A1 (it) * | 2009-08-07 | 2011-02-08 | Inalco S P A A Socio Unico | Derivati semi-sintetici del polisaccaride k5 per la prevenzione ed il trattamento del danno tissutale associato a ischemia e/o riperfusione |
| CN102712942B (zh) * | 2009-09-01 | 2014-05-14 | 伦斯勒理工学院 | K5肝素前体的发酵和纯化 |
| WO2012016216A2 (en) | 2010-07-29 | 2012-02-02 | Shire Human Genetic Therapies | Assays for detection of glycosaminoglycans |
| WO2013116677A2 (en) * | 2012-02-01 | 2013-08-08 | Shire Human Genetic Therapies, Inc. | Assays for detection of glycosaminoglycans |
| CN102796723A (zh) * | 2012-09-11 | 2012-11-28 | 深圳市海普瑞药业股份有限公司 | 肝素酶i的固定化方法 |
| CN102888390B (zh) * | 2012-10-30 | 2014-09-03 | 深圳市海普瑞药业股份有限公司 | 肝素酶ⅲ的固定化方法 |
| CN103059165B (zh) * | 2012-12-26 | 2015-04-29 | 安徽丰原药业股份有限公司 | 一种多糖酰化物及其制备方法 |
| EP3399044B1 (en) | 2015-12-28 | 2021-02-03 | Ajinomoto Co., Inc. | Method for producing heparan sulfate having anticoagulant activity |
| JP6225321B1 (ja) * | 2016-08-31 | 2017-11-08 | 王子ホールディングス株式会社 | ポリ硫酸ペントサンの製造方法 |
| CN111148749A (zh) | 2016-08-31 | 2020-05-12 | 王子控股株式会社 | 酸性低聚木糖的生产方法和酸性低聚木糖 |
| JP6281659B1 (ja) | 2017-02-28 | 2018-02-21 | 王子ホールディングス株式会社 | ポリ硫酸ペントサン、医薬組成物及び抗凝固剤 |
| US11278485B2 (en) | 2017-05-31 | 2022-03-22 | Oji Holdings Corporation | Moisturizing topical preparation |
| SG11202002250VA (en) | 2017-09-12 | 2020-04-29 | Oji Holdings Corp | Pentosan polysulfate and method for producing pentosan polysulfate |
| EP3730521B1 (en) | 2017-12-20 | 2023-05-17 | Oji Holdings Corporation | Pentosan polysulfate and medicine containing pentosan polysulfate |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1214609B (it) * | 1985-05-17 | 1990-01-18 | Opocrin Spa | Esosaminoglicani solfati depolimerizzati ad attivita'antitrombotica, fibrinolitica, antinfiammatoria, loro procedimento di preparazione e composizioni farmaceutiche che li contengono. |
| FR2669932B1 (fr) * | 1990-12-03 | 1994-07-01 | Sanofi Sa | Nouvel heparosane-n,o-sulfate, son procede de preparation et les compositions pharmaceutiques qui le contiennent. |
| IT1271057B (it) | 1994-11-04 | 1997-05-26 | Inalco Spa | Polisaccaridi aventi un elevato contenuto di acido iduronico |
| IT1282994B1 (it) * | 1996-05-10 | 1998-04-03 | Inalco Spa | Derivati del polisaccaride k5 aventi elevata attivita' anticoagulante |
| IT1290814B1 (it) | 1997-03-24 | 1998-12-11 | Istituto Scient Di Chimica E B | Glicosaminoglicani aventi elevata attivita' antitrombotica |
| SE9701454D0 (sv) | 1997-04-18 | 1997-04-18 | Ulf Lindahl | new DNA sequences and a process for enzyme manufacture |
| IT1318432B1 (it) * | 2000-03-30 | 2003-08-25 | Inalco Spa | Glicosaminoglicani derivati dal polisaccaride k5 aventi elevataattivita' anticoagulante ed antitrombotica e processo per la loro |
| US20020062019A1 (en) * | 2000-03-30 | 2002-05-23 | Pasqua Oreste | Glycosaminoglycans derived from K5 polysaccharide having high anticoagulant and antithrombotic activities and process for their preparation |
| ITMI20011633A1 (it) * | 2001-07-27 | 2003-01-27 | San Raffaele Centro Fond | Uso di polisaccaridi batterici supersolfatati inibitori dell'hiv |
| DE60334617D1 (de) * | 2002-06-18 | 2010-12-02 | Glycores 2000 Srl | Epimerderivate von k5-polysaccharid mit hohem sulfatierungsgrad |
-
2003
- 2003-08-06 IT IT001618A patent/ITMI20031618A1/it unknown
-
2004
- 2004-07-07 CN CNA2004800223076A patent/CN1832966A/zh active Pending
- 2004-07-07 RU RU2006106790/04A patent/RU2361881C2/ru not_active IP Right Cessation
- 2004-07-07 WO PCT/EP2004/051391 patent/WO2005014656A1/en not_active Ceased
- 2004-07-07 JP JP2006522341A patent/JP2007501305A/ja active Pending
- 2004-07-07 MX MXPA06001511A patent/MXPA06001511A/es active IP Right Grant
- 2004-07-07 CA CA002534709A patent/CA2534709A1/en not_active Abandoned
- 2004-07-07 BR BRPI0413346-3A patent/BRPI0413346A/pt not_active IP Right Cessation
- 2004-07-07 AT AT04766148T patent/ATE458009T1/de not_active IP Right Cessation
- 2004-07-07 EP EP04766148A patent/EP1654288B9/en not_active Expired - Lifetime
- 2004-07-07 ES ES04766148T patent/ES2341249T3/es not_active Expired - Lifetime
- 2004-07-07 DE DE602004025583T patent/DE602004025583D1/de not_active Expired - Fee Related
- 2004-07-07 US US10/557,584 patent/US7687249B2/en not_active Expired - Fee Related
- 2004-07-07 AU AU2004262584A patent/AU2004262584A1/en not_active Abandoned
- 2004-07-07 DK DK04766148.3T patent/DK1654288T3/da active
- 2004-07-07 KR KR1020067002532A patent/KR20060063933A/ko not_active Withdrawn
-
2006
- 2006-01-31 IL IL173482A patent/IL173482A0/en unknown
- 2006-02-24 ZA ZA200601643A patent/ZA200601643B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ITMI20031618A1 (it) | 2005-02-07 |
| US7687249B2 (en) | 2010-03-30 |
| RU2361881C2 (ru) | 2009-07-20 |
| EP1654288A1 (en) | 2006-05-10 |
| EP1654288B1 (en) | 2010-02-17 |
| JP2007501305A (ja) | 2007-01-25 |
| DK1654288T3 (da) | 2010-09-20 |
| US20070042993A1 (en) | 2007-02-22 |
| ATE458009T1 (de) | 2010-03-15 |
| ES2341249T3 (es) | 2010-06-17 |
| ZA200601643B (en) | 2007-05-30 |
| IL173482A0 (en) | 2006-06-11 |
| DE602004025583D1 (de) | 2010-04-01 |
| BRPI0413346A (pt) | 2006-10-10 |
| WO2005014656A1 (en) | 2005-02-17 |
| CN1832966A (zh) | 2006-09-13 |
| EP1654288B9 (en) | 2010-06-23 |
| CA2534709A1 (en) | 2005-02-17 |
| KR20060063933A (ko) | 2006-06-12 |
| MXPA06001511A (es) | 2006-05-15 |
| RU2006106790A (ru) | 2007-09-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1654288B1 (en) | Polysaccharides derivatives with high antithrombotic activity in plasma | |
| US5550116A (en) | N,O-sulphated heparosans and pharmaceutical compositions containing them | |
| US5384398A (en) | High molecular mass N,O-sulphated heparosans, process for their preparation and the pharmaceutical compositions which contain them | |
| CA2432150C (en) | Glycosaminoglycans derived from k5 polysaccharide having high antithrombin activity and process for their preparation | |
| US8227449B2 (en) | Glycosaminoglycans derived from K5 polysaccharide having high anticoagulant and antithrombotic activities and process for their preparation | |
| RU2283319C2 (ru) | Гликозаминогликаны, производные к5-полисахарида, обладающие высокой антикоагулянтной и антитромботической активностью, и способ их получения | |
| US7812151B2 (en) | Low molecular weight polysaccharides having antithrombotic activity | |
| MXPA04012714A (es) | Derivados epimerizados del polisacarido k5 con un grado muy alto de sulfatacion. | |
| US20050027117A1 (en) | Anticoagulant and antithrombotic LMW-glycosaminoglycans derived from K5 polysaccharide and process for their preparation | |
| AU2002222358B2 (en) | Glycosaminoglycans derived from K5 polysaccharide having high antithrombin activity and process for their preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |