CA2533555A1 - Melanges d'oligosaccharides derives d'heparine, leur preparation et les compositions pharmaceutiques les contenant - Google Patents
Melanges d'oligosaccharides derives d'heparine, leur preparation et les compositions pharmaceutiques les contenant Download PDFInfo
- Publication number
- CA2533555A1 CA2533555A1 CA002533555A CA2533555A CA2533555A1 CA 2533555 A1 CA2533555 A1 CA 2533555A1 CA 002533555 A CA002533555 A CA 002533555A CA 2533555 A CA2533555 A CA 2533555A CA 2533555 A1 CA2533555 A1 CA 2533555A1
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- CA
- Canada
- Prior art keywords
- heparin
- activity
- molecular weight
- mixtures
- salt
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 87
- 229920000669 heparin Polymers 0.000 title claims abstract description 73
- 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 title claims abstract description 69
- 229960002897 heparin Drugs 0.000 title claims abstract description 52
- 229920001542 oligosaccharide Polymers 0.000 title claims abstract description 50
- 150000002482 oligosaccharides Chemical class 0.000 title claims abstract description 50
- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 74
- 230000000694 effects Effects 0.000 claims abstract description 73
- 230000008569 process Effects 0.000 claims abstract description 55
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 300
- 239000000243 solution Substances 0.000 claims description 77
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 60
- 159000000000 sodium salts Chemical class 0.000 claims description 58
- -1 alkaline earth metal salt Chemical class 0.000 claims description 56
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 50
- SIYLLGKDQZGJHK-UHFFFAOYSA-N dimethyl-(phenylmethyl)-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethyl]ammonium Chemical compound C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 SIYLLGKDQZGJHK-UHFFFAOYSA-N 0.000 claims description 32
- 239000011734 sodium Substances 0.000 claims description 29
- 230000001858 anti-Xa Effects 0.000 claims description 28
- 230000032050 esterification Effects 0.000 claims description 28
- 238000005886 esterification reaction Methods 0.000 claims description 28
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 24
- 239000001632 sodium acetate Substances 0.000 claims description 22
- 235000017281 sodium acetate Nutrition 0.000 claims description 22
- 239000002585 base Substances 0.000 claims description 17
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 16
- 229910052708 sodium Inorganic materials 0.000 claims description 15
- 150000002148 esters Chemical class 0.000 claims description 13
- 238000000746 purification Methods 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 12
- 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 claims description 10
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 claims description 10
- 229960001950 benzethonium chloride Drugs 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 229940127215 low-molecular weight heparin Drugs 0.000 claims description 10
- GKTNLYAAZKKMTQ-UHFFFAOYSA-N n-[bis(dimethylamino)phosphinimyl]-n-methylmethanamine Chemical class CN(C)P(=N)(N(C)C)N(C)C GKTNLYAAZKKMTQ-UHFFFAOYSA-N 0.000 claims description 10
- 238000007127 saponification reaction Methods 0.000 claims description 10
- 239000003055 low molecular weight heparin Substances 0.000 claims description 9
- 239000002609 medium Substances 0.000 claims description 9
- 230000009466 transformation Effects 0.000 claims description 9
- VSCBATMPTLKTOV-UHFFFAOYSA-N 2-tert-butylimino-n,n-diethyl-1,3-dimethyl-1,3,2$l^{5}-diazaphosphinan-2-amine Chemical compound CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C VSCBATMPTLKTOV-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 7
- 229960003872 benzethonium Drugs 0.000 claims description 7
- 108010074860 Factor Xa Proteins 0.000 claims description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 229920002401 polyacrylamide Polymers 0.000 claims description 6
- 238000004587 chromatography analysis Methods 0.000 claims description 5
- 150000002016 disaccharides Chemical class 0.000 claims description 5
- 229960000610 enoxaparin Drugs 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 150000004044 tetrasaccharides Chemical class 0.000 claims description 5
- 229920000936 Agarose Polymers 0.000 claims description 4
- 230000009471 action Effects 0.000 claims description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 4
- 239000000470 constituent Substances 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- CTSLUCNDVMMDHG-UHFFFAOYSA-N 5-bromo-3-(butan-2-yl)-6-methylpyrimidine-2,4(1H,3H)-dione Chemical compound CCC(C)N1C(=O)NC(C)=C(Br)C1=O CTSLUCNDVMMDHG-UHFFFAOYSA-N 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- 206010047249 Venous thrombosis Diseases 0.000 claims description 3
- 230000001476 alcoholic effect Effects 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- RLGQACBPNDBWTB-UHFFFAOYSA-N cetyltrimethylammonium ion Chemical class CCCCCCCCCCCCCCCC[N+](C)(C)C RLGQACBPNDBWTB-UHFFFAOYSA-N 0.000 claims description 3
- 229940087051 fragmin Drugs 0.000 claims description 3
- 150000004676 glycans Chemical class 0.000 claims description 3
- 229940095443 innohep Drugs 0.000 claims description 3
- 150000007530 organic bases Chemical class 0.000 claims description 3
- 229920001282 polysaccharide Polymers 0.000 claims description 3
- 239000005017 polysaccharide Substances 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- SYRHIZPPCHMRIT-UHFFFAOYSA-N tin(4+) Chemical compound [Sn+4] SYRHIZPPCHMRIT-UHFFFAOYSA-N 0.000 claims description 3
- 206010002388 Angina unstable Diseases 0.000 claims description 2
- 206010003178 Arterial thrombosis Diseases 0.000 claims description 2
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 206010003658 Atrial Fibrillation Diseases 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 239000008118 PEG 6000 Substances 0.000 claims description 2
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 2
- 206010038923 Retinopathy Diseases 0.000 claims description 2
- 208000007814 Unstable Angina Diseases 0.000 claims description 2
- 230000003030 amydolytic effect Effects 0.000 claims description 2
- 230000033115 angiogenesis Effects 0.000 claims description 2
- 230000002785 anti-thrombosis Effects 0.000 claims description 2
- 239000012736 aqueous medium Substances 0.000 claims description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
- 210000001367 artery Anatomy 0.000 claims description 2
- 239000000872 buffer Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 150000001720 carbohydrates Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 229960004830 cetylpyridinium Drugs 0.000 claims description 2
- NEUSVAOJNUQRTM-UHFFFAOYSA-N cetylpyridinium Chemical compound CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 NEUSVAOJNUQRTM-UHFFFAOYSA-N 0.000 claims description 2
- 238000012691 depolymerization reaction Methods 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229910000000 metal hydroxide Inorganic materials 0.000 claims description 2
- 150000004692 metal hydroxides Chemical class 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 230000002093 peripheral effect Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 230000002685 pulmonary effect Effects 0.000 claims description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 2
- 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 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 230000004663 cell proliferation Effects 0.000 claims 1
- 239000003593 chromogenic compound Substances 0.000 claims 1
- 208000019622 heart disease Diseases 0.000 claims 1
- 238000002347 injection Methods 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- 208000028867 ischemia Diseases 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 238000006116 polymerization reaction Methods 0.000 claims 1
- 239000003981 vehicle Substances 0.000 claims 1
- 239000006228 supernatant Substances 0.000 description 50
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 238000003756 stirring Methods 0.000 description 32
- 239000000725 suspension Substances 0.000 description 30
- 239000013049 sediment Substances 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- 239000012528 membrane Substances 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 16
- 235000011121 sodium hydroxide Nutrition 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 239000011780 sodium chloride Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 108090000935 Antithrombin III Proteins 0.000 description 5
- 238000013019 agitation Methods 0.000 description 5
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 5
- 229940073608 benzyl chloride Drugs 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000012429 reaction media Substances 0.000 description 5
- 102100022977 Antithrombin-III Human genes 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 230000019635 sulfation Effects 0.000 description 4
- 238000005670 sulfation reaction Methods 0.000 description 4
- PXFBZOLANLWPMH-UHFFFAOYSA-N 16-Epiaffinine Natural products C1C(C2=CC=CC=C2N2)=C2C(=O)CC2C(=CC)CN(C)C1C2CO PXFBZOLANLWPMH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000004321 preservation Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- IIPYXGDZVMZOAP-UHFFFAOYSA-N lithium nitrate Chemical compound [Li+].[O-][N+]([O-])=O IIPYXGDZVMZOAP-UHFFFAOYSA-N 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 2
- RPEUKYFRIGEOOE-UHFFFAOYSA-N 1,3-dimethyl-1,3,2-diazaphosphinane Chemical compound CN1CCCN(C)P1 RPEUKYFRIGEOOE-UHFFFAOYSA-N 0.000 description 1
- MAJHARAMJPZOIK-UHFFFAOYSA-N 1h-1,3,2-diazaphosphinin-2-amine Chemical compound NP1NC=CC=N1 MAJHARAMJPZOIK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 102000004411 Antithrombin III Human genes 0.000 description 1
- GDQHWYANHAJERO-UHFFFAOYSA-N CN(C)[PH2](N(C)C)N(C)C Chemical compound CN(C)[PH2](N(C)C)N(C)C GDQHWYANHAJERO-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 102100021194 Glypican-6 Human genes 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 229910014142 Na—O Inorganic materials 0.000 description 1
- RSPISYXLHRIGJD-UHFFFAOYSA-N OOOO Chemical compound OOOO RSPISYXLHRIGJD-UHFFFAOYSA-N 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 230000003024 amidolytic effect Effects 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229960005348 antithrombin iii Drugs 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 1
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
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- 230000023597 hemostasis Effects 0.000 description 1
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- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
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- 239000002808 molecular sieve Substances 0.000 description 1
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- GUAQVFRUPZBRJQ-UHFFFAOYSA-N n-(3-aminopropyl)-2-methylprop-2-enamide Chemical compound CC(=C)C(=O)NCCCN GUAQVFRUPZBRJQ-UHFFFAOYSA-N 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 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
-
- 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
- C08B37/0078—Degradation products
-
- 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
- A61K31/727—Heparin; Heparan
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Molecular Biology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Polymers & Plastics (AREA)
- Materials Engineering (AREA)
- Biochemistry (AREA)
- Emergency Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0309041A FR2857971B1 (fr) | 2003-07-24 | 2003-07-24 | Melanges d'oligosaccharides derives d'heparine, leur preparation et les compositions pharmaceutiques les contenant |
| FR0309041 | 2003-07-24 | ||
| PCT/FR2004/001943 WO2005010051A2 (fr) | 2003-07-24 | 2004-07-22 | Melanges d'oligosaccharides derives d'heparine, leur preparation et les compositions pharmaceutiques les contenant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2533555A1 true CA2533555A1 (fr) | 2005-02-03 |
Family
ID=33561051
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002533555A Abandoned CA2533555A1 (fr) | 2003-07-24 | 2004-07-22 | Melanges d'oligosaccharides derives d'heparine, leur preparation et les compositions pharmaceutiques les contenant |
Country Status (39)
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7589145B2 (en) | 2004-04-15 | 2009-09-15 | Exxonmobil Chemical Patents Inc. | Syndiotactic rich polyolefins |
| EP2447285A3 (en) * | 2006-05-25 | 2013-01-16 | Momenta Pharmaceuticals, Inc. | Low molecular weight heparin composition and uses thereof |
| CN101711771B (zh) * | 2008-10-07 | 2015-12-09 | 上海喜恩医药科技发展有限公司 | 一种肝素衍生的多糖混合物及其制法和药物组合物 |
| DK3144325T3 (da) * | 2010-09-14 | 2021-01-25 | Univ Miyazaki | Heparin med høj renhed og fremstillingsfremgangsmåde dertil |
| WO2012072799A1 (en) | 2010-12-02 | 2012-06-07 | Aventis Pharma S.A. | New methods for the in vitro measurement of the biological activity of an ultra low molecular weight heparin sample |
| CN102558392A (zh) * | 2010-12-14 | 2012-07-11 | 王芃 | 一种高抗FXa、低抗FIIa低分子肝素钠的制备方法 |
| CN102816255B (zh) * | 2011-06-10 | 2015-11-25 | 王芃 | 一种超低分子肝素钠的制备方法 |
| EP2980103B1 (en) | 2013-03-26 | 2020-11-04 | Jiuzhitang Co., Ltd. | Low molecular weight glycosaminoglycan derivative, pharmaceutical composition thereof, preparation method therefor and use thereof |
| CN103864959A (zh) * | 2014-04-03 | 2014-06-18 | 中国药科大学 | 一种肝素十二糖抗动脉粥样硬化的用途 |
| RU2639574C2 (ru) * | 2016-05-23 | 2017-12-21 | Алексей Георгиевич Александров | Способ получения низкомолекулярного гепарина |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL61201A (en) * | 1979-10-05 | 1984-09-30 | Choay Sa | Oligosaccharides having no more than 8 saccharide moieties,their obtention from heparin and pharmaceutical compositions containing them |
| FR2504928A1 (fr) * | 1981-04-29 | 1982-11-05 | Choay Sa | Oligosaccharides a chaines courtes possedant des proprietes biologiques, leur preparation et leurs applications en tant que medicaments |
| 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. |
| IT1284143B1 (it) * | 1996-09-06 | 1998-05-08 | Istituto Scient Di Chimica E B | Eparansolfati semi-sintetici ad elevata attivita' antimetastica e ridotto rischio emorragico |
| AU7753898A (en) * | 1997-06-06 | 1998-12-21 | Hamilton Civic Hospitals Research Development, Inc. | Modified low molecular weight heparin that inhibits clot associated coagulation factors |
| ES2161615B1 (es) * | 1999-07-23 | 2003-03-16 | Rovi Lab Farmaceut Sa | Composiciones de heparinas de muy bajo peso molecular. |
| JP4897991B2 (ja) * | 1999-07-23 | 2012-03-14 | ラボラトリオス ファルマセウティコス ロビ ソシエダッド アノニマ | 超低分子量ヘパリン組成物 |
| FR2800074B1 (fr) * | 1999-10-22 | 2001-12-21 | Aventis Pharma Sa | Nouveaux oligosaccharides, leur preparation et les compositions pharmaceutiques les contenant |
| JP4585072B2 (ja) * | 2000-02-29 | 2010-11-24 | 扶桑薬品工業株式会社 | ヘパリン解重合法、解重合ヘパリン、その誘導体および医薬組成物 |
| FR2807043B1 (fr) * | 2000-03-28 | 2002-11-22 | Aventis Pharma Sa | Composition pharmaceutique contenant des oligosaccharides, les nouveaux oligosaccharides et leur preparation |
| US6969705B2 (en) * | 2000-07-21 | 2005-11-29 | Aventis Pharma S.A. | Compositions of polysaccharides derived from heparin, their preparation and pharmaceutical compositions containing them |
| FR2811992B1 (fr) * | 2000-07-21 | 2003-07-04 | Aventis Pharma Sa | Melanges de polysaccharides derives d'heparine, leur preparation et les compositions pharmaceutiques les contenant |
| CA2458852A1 (en) * | 2001-08-28 | 2003-03-06 | Leo Pharma A/S | Antithrombotic compositions comprising low molecular weight heparin and low molecular weight dermatan sulphate |
| FR2845686B1 (fr) * | 2002-10-10 | 2013-08-30 | Aventis Pharma Sa | Melanges de polysaccharides derives d'heparine, leur preparation et les compositions pharmaceutiques les contenant |
-
2003
- 2003-07-24 FR FR0309041A patent/FR2857971B1/fr not_active Expired - Fee Related
-
2004
- 2004-07-01 PE PE2004000632A patent/PE20050246A1/es not_active Application Discontinuation
- 2004-07-14 PA PA20048606801A patent/PA8606801A1/es unknown
- 2004-07-19 AR ARP040102549A patent/AR045917A1/es not_active Application Discontinuation
- 2004-07-21 HN HN2004000250A patent/HN2004000250A/es unknown
- 2004-07-22 DE DE602004030015T patent/DE602004030015D1/de not_active Expired - Lifetime
- 2004-07-22 SI SI200431594T patent/SI1651677T1/sl unknown
- 2004-07-22 RS YUP-2006/0044A patent/RS20060044A/sr unknown
- 2004-07-22 UA UAA200601969A patent/UA89356C2/ru unknown
- 2004-07-22 BR BRPI0412850-8A patent/BRPI0412850A/pt active Search and Examination
- 2004-07-22 PL PL04785991T patent/PL1651677T3/pl unknown
- 2004-07-22 ME MEP-116/08A patent/MEP11608A/xx unknown
- 2004-07-22 PT PT04785991T patent/PT1651677E/pt unknown
- 2004-07-22 CN CN2004800265420A patent/CN1852926B/zh not_active Expired - Fee Related
- 2004-07-22 AT AT04785991T patent/ATE487741T1/de active
- 2004-07-22 NZ NZ544717A patent/NZ544717A/en unknown
- 2004-07-22 KR KR1020067001609A patent/KR101125517B1/ko not_active Expired - Fee Related
- 2004-07-22 CA CA002533555A patent/CA2533555A1/fr not_active Abandoned
- 2004-07-22 JP JP2006520862A patent/JP4865552B2/ja not_active Expired - Fee Related
- 2004-07-22 MX MXPA06000336A patent/MXPA06000336A/es active IP Right Grant
- 2004-07-22 DK DK04785991.3T patent/DK1651677T3/da active
- 2004-07-22 WO PCT/FR2004/001943 patent/WO2005010051A2/fr not_active Ceased
- 2004-07-22 MY MYPI20042944A patent/MY136769A/en unknown
- 2004-07-22 AU AU2004259111A patent/AU2004259111B2/en not_active Ceased
- 2004-07-22 RU RU2006105384/04A patent/RU2346005C2/ru not_active IP Right Cessation
- 2004-07-22 ES ES04785991T patent/ES2355827T3/es not_active Expired - Lifetime
- 2004-07-22 EP EP04785991A patent/EP1651677B1/fr not_active Expired - Lifetime
- 2004-07-22 OA OA1200600025A patent/OA13197A/fr unknown
- 2004-07-23 UY UY28435A patent/UY28435A1/es unknown
- 2004-07-23 TW TW093121979A patent/TWI369208B/zh not_active IP Right Cessation
- 2004-07-23 GT GT200400145A patent/GT200400145A/es unknown
-
2006
- 2006-01-17 IL IL173206A patent/IL173206A/en not_active IP Right Cessation
- 2006-01-18 CR CR8201A patent/CR8201A/es unknown
- 2006-01-20 MA MA28745A patent/MA27928A1/fr unknown
- 2006-01-23 TN TNP2006000025A patent/TNSN06025A1/en unknown
- 2006-01-23 ZA ZA200600657A patent/ZA200600657B/en unknown
- 2006-01-23 EC EC2006006305A patent/ECSP066305A/es unknown
- 2006-02-20 NO NO20060821A patent/NO20060821L/no not_active Application Discontinuation
-
2011
- 2011-02-04 CY CY20111100132T patent/CY1111165T1/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20140424 |