RU2617764C2 - Неантикоагулянтные гликозаминогликаны, содержащие повторяющиеся дисахаридные звенья, и их медицинское применение - Google Patents
Неантикоагулянтные гликозаминогликаны, содержащие повторяющиеся дисахаридные звенья, и их медицинское применение Download PDFInfo
- Publication number
- RU2617764C2 RU2617764C2 RU2014129816A RU2014129816A RU2617764C2 RU 2617764 C2 RU2617764 C2 RU 2617764C2 RU 2014129816 A RU2014129816 A RU 2014129816A RU 2014129816 A RU2014129816 A RU 2014129816A RU 2617764 C2 RU2617764 C2 RU 2617764C2
- Authority
- RU
- Russia
- Prior art keywords
- glycosaminoglycan
- heparin
- chemically modified
- molecular weight
- solution
- Prior art date
Links
- 229920002683 Glycosaminoglycan Polymers 0.000 title claims abstract description 88
- 239000003146 anticoagulant agent Substances 0.000 title description 2
- 229940127219 anticoagulant drug Drugs 0.000 title description 2
- 125000000600 disaccharide group Chemical group 0.000 title 1
- 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 claims abstract description 122
- 229960002897 heparin Drugs 0.000 claims abstract description 118
- 230000000694 effects Effects 0.000 claims abstract description 35
- 229920002971 Heparan sulfate Polymers 0.000 claims abstract description 27
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 229920000669 heparin Polymers 0.000 claims description 119
- 238000000034 method Methods 0.000 claims description 93
- 150000004676 glycans Polymers 0.000 claims description 53
- 238000007254 oxidation reaction Methods 0.000 claims description 47
- 230000003647 oxidation Effects 0.000 claims description 45
- 150000004804 polysaccharides Polymers 0.000 claims description 44
- 238000006243 chemical reaction Methods 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 22
- 230000002429 anti-coagulating effect Effects 0.000 claims description 20
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 claims description 20
- 230000008569 process Effects 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 16
- 238000009826 distribution Methods 0.000 claims description 16
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 14
- 229910052740 iodine Inorganic materials 0.000 claims description 14
- 239000011630 iodine Substances 0.000 claims description 14
- 102000004169 proteins and genes Human genes 0.000 claims description 14
- 108090000623 proteins and genes Proteins 0.000 claims description 14
- 230000009467 reduction Effects 0.000 claims description 14
- 150000002302 glucosamines Chemical class 0.000 claims description 13
- 150000007513 acids Chemical class 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 10
- 230000001590 oxidative effect Effects 0.000 claims description 10
- 150000002016 disaccharides Chemical group 0.000 claims description 9
- 229920001282 polysaccharide Polymers 0.000 claims description 9
- 239000005017 polysaccharide Substances 0.000 claims description 9
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 claims description 8
- 230000003511 endothelial effect Effects 0.000 claims description 7
- 125000003172 aldehyde group Chemical group 0.000 claims description 6
- 150000001720 carbohydrates Chemical class 0.000 claims description 6
- 239000003638 chemical reducing agent Substances 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 230000006641 stabilisation Effects 0.000 claims description 4
- 238000011105 stabilization Methods 0.000 claims description 4
- 238000007385 chemical modification Methods 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 208000010515 dystocia Diseases 0.000 claims 5
- 230000006806 disease prevention Effects 0.000 claims 2
- 239000000126 substance Substances 0.000 abstract description 8
- 239000000243 solution Substances 0.000 description 104
- 239000000047 product Substances 0.000 description 65
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 230000014508 negative regulation of coagulation Effects 0.000 description 33
- 229940127215 low-molecular weight heparin Drugs 0.000 description 23
- 239000003055 low molecular weight heparin Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 238000001556 precipitation Methods 0.000 description 17
- 239000008213 purified water Substances 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 239000007800 oxidant agent Substances 0.000 description 14
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 239000004019 antithrombin Substances 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 230000008030 elimination Effects 0.000 description 12
- 238000003379 elimination reaction Methods 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 239000012279 sodium borohydride Substances 0.000 description 11
- 229910000033 sodium borohydride Inorganic materials 0.000 description 11
- 238000007068 beta-elimination reaction Methods 0.000 description 10
- 239000012452 mother liquor Substances 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 238000007920 subcutaneous administration Methods 0.000 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 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 208000032843 Hemorrhage Diseases 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
- 208000034158 bleeding Diseases 0.000 description 6
- 230000000740 bleeding effect Effects 0.000 description 6
- 239000007853 buffer solution Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000002349 favourable effect Effects 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 239000012429 reaction media Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000011084 recovery Methods 0.000 description 6
- 241000872931 Myoporum sandwicense Species 0.000 description 5
- 208000007536 Thrombosis Diseases 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 229960004969 dalteparin Drugs 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102100030009 Azurocidin Human genes 0.000 description 4
- 101710154607 Azurocidin Proteins 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 239000008186 active pharmaceutical agent Substances 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 4
- 230000023555 blood coagulation Effects 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 229940088679 drug related substance Drugs 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 229960002442 glucosamine Drugs 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- IAJILQKETJEXLJ-LECHCGJUSA-N iduronic acid Chemical group O=C[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-LECHCGJUSA-N 0.000 description 4
- 210000004400 mucous membrane Anatomy 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 3
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 206010036872 Prolonged labour Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000003114 blood coagulation factor Substances 0.000 description 3
- 239000008366 buffered solution Substances 0.000 description 3
- 210000003679 cervix uteri Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 238000002845 discoloration Methods 0.000 description 3
- 229940126534 drug product Drugs 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 229940097043 glucuronic acid Drugs 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 230000007012 clinical effect Effects 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000011194 good manufacturing practice Methods 0.000 description 2
- 239000002628 heparin derivative Substances 0.000 description 2
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 description 2
- 150000002497 iodine compounds Chemical class 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- -1 periodate compound Chemical class 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 206010043554 thrombocytopenia Diseases 0.000 description 2
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 108090000935 Antithrombin III Proteins 0.000 description 1
- 102100022977 Antithrombin-III Human genes 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 229920002271 DEAE-Sepharose Polymers 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- 208000034423 Delivery Diseases 0.000 description 1
- 101710141457 Histidine-binding periplasmic protein Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000004890 Interleukin-8 Human genes 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 102400000050 Oxytocin Human genes 0.000 description 1
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 description 1
- 101800000989 Oxytocin Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 101710092628 Probable histidine-binding protein Proteins 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 229940122055 Serine protease inhibitor Drugs 0.000 description 1
- 101710102218 Serine protease inhibitor Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 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
- 239000002738 chelating agent Substances 0.000 description 1
- 230000002925 chemical effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 239000012501 chromatography medium Substances 0.000 description 1
- 230000003749 cleanliness Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000005115 demineralization Methods 0.000 description 1
- 230000002328 demineralizing effect Effects 0.000 description 1
- 238000012691 depolymerization reaction Methods 0.000 description 1
- 238000010612 desalination reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 229960000610 enoxaparin Drugs 0.000 description 1
- 208000037902 enteropathy Diseases 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000002692 epidural anesthesia Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004992 fission Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 150000002337 glycosamines Chemical class 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 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 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000003027 hypercoagulation Effects 0.000 description 1
- 230000000023 hypocoagulative effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 1
- 229940096397 interleukin-8 Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 1
- 229960001723 oxytocin Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000010951 particle size reduction Methods 0.000 description 1
- 229940023462 paste product Drugs 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-M periodate Chemical compound [O-]I(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-M 0.000 description 1
- 239000008196 pharmacological composition Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000003331 prothrombotic effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000007391 self-medication Methods 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 230000009677 vaginal delivery Effects 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
Images
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
- C08B37/0075—Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/04—Drugs for genital or sexual disorders; Contraceptives for inducing labour or abortion; Uterotonics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Polymers & Plastics (AREA)
- Pregnancy & Childbirth (AREA)
- Gynecology & Obstetrics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161577223P | 2011-12-19 | 2011-12-19 | |
| US61/577,223 | 2011-12-19 | ||
| PCT/SE2012/051433 WO2013095279A1 (en) | 2011-12-19 | 2012-12-19 | Non anti-coagulative glycosaminoglycans comprising repeating disaccharide unit and their medical use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2014129816A RU2014129816A (ru) | 2016-02-20 |
| RU2617764C2 true RU2617764C2 (ru) | 2017-04-26 |
Family
ID=48668970
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2014129816A RU2617764C2 (ru) | 2011-12-19 | 2012-12-19 | Неантикоагулянтные гликозаминогликаны, содержащие повторяющиеся дисахаридные звенья, и их медицинское применение |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US9475888B2 (enExample) |
| EP (1) | EP2794665B1 (enExample) |
| JP (2) | JP6543467B2 (enExample) |
| KR (1) | KR102135485B1 (enExample) |
| CN (1) | CN104144950B (enExample) |
| AU (1) | AU2012354229B2 (enExample) |
| BR (1) | BR112014014454B1 (enExample) |
| CA (1) | CA2856492C (enExample) |
| CL (1) | CL2014001651A1 (enExample) |
| CO (1) | CO7061069A2 (enExample) |
| CY (1) | CY1119899T1 (enExample) |
| DK (1) | DK2794665T3 (enExample) |
| ES (1) | ES2656613T3 (enExample) |
| HR (1) | HRP20180124T1 (enExample) |
| HU (1) | HUE036523T2 (enExample) |
| IL (1) | IL232905A (enExample) |
| LT (1) | LT2794665T (enExample) |
| ME (1) | ME02994B (enExample) |
| MX (1) | MX351104B (enExample) |
| NO (1) | NO2904345T3 (enExample) |
| PL (1) | PL2794665T3 (enExample) |
| PT (1) | PT2794665T (enExample) |
| RS (1) | RS56874B1 (enExample) |
| RU (1) | RU2617764C2 (enExample) |
| SI (1) | SI2794665T1 (enExample) |
| SM (1) | SMT201800143T1 (enExample) |
| WO (1) | WO2013095279A1 (enExample) |
| ZA (1) | ZA201403640B (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013095215A1 (en) | 2011-12-19 | 2013-06-27 | Dilaforette Ab | Low anticoagulant heparins |
| EP2830635A4 (en) * | 2012-03-26 | 2016-03-16 | Dilafor Ab | COMBINATION TREATMENT OF ILLUSTRATED SULFATED GLYCOSAMINOGLYCANES |
| CN104244957B (zh) * | 2012-03-26 | 2017-11-17 | 迪乐方有限责任公司 | 用于治疗分娩停止的方法 |
| UA117912C2 (uk) * | 2012-05-08 | 2018-10-25 | Ділафор Аб | Застосування гепарину або гепарансульфату для лікування післяпологової кровотечі (ппк) |
| GB2515315A (en) * | 2013-06-19 | 2014-12-24 | Dilafor Ab | New Processes |
| CN103788222B (zh) * | 2014-01-08 | 2016-08-31 | 中国科学院昆明植物研究所 | Fuc3S4S取代的低聚糖胺聚糖及其制备方法 |
| EP3137509A4 (en) * | 2014-04-30 | 2018-03-14 | Agency For Science, Technology And Research | Heparan sulphates |
| CN108424474B (zh) * | 2017-02-15 | 2023-07-25 | 清华大学 | 去抗凝肝素衍生物及其用于炎症性肠病的治疗 |
| UA129730C2 (uk) | 2020-02-17 | 2025-07-16 | Дилафор Аб | Тафоксипарин для лікування прееклампсії |
| EP4272749A1 (en) | 2022-05-03 | 2023-11-08 | Dilafor AB | New medical use of tafoxiparin |
| JP2025514038A (ja) | 2022-05-03 | 2025-05-02 | ディラフォール アクチエボラグ | タフォキシパリンの新規な医学的使用 |
| GB202407366D0 (en) * | 2024-05-23 | 2024-07-10 | Glycos Biomedical Ltd | Preparation of medium molecular weight heparin |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0735050A2 (en) * | 1995-03-31 | 1996-10-02 | Hamilton Civic Hospitals Research Development, Inc. | Compositions for inhibiting thrombogenesis |
| US5767269A (en) * | 1996-10-01 | 1998-06-16 | Hamilton Civic Hospitals Research Development Inc. | Processes for the preparation of low-affinity, low molecular weight heparins useful as antithrombotics |
| WO2009007224A1 (en) * | 2007-07-10 | 2009-01-15 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Low molecular weight heparin derivatives having neuroprotective activity |
| RU2010122324A (ru) * | 2007-11-02 | 2011-12-10 | Момента Фармасьютикалз, Инк. (Us) | Полисахаридные композиции, не обладающие антикоагулянтными свойствами |
Family Cites Families (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1136620A (en) | 1979-01-08 | 1982-11-30 | Ulf P.F. Lindahl | Heparin fragments having selective anticoagulation activity |
| JPS63246396A (ja) * | 1987-03-31 | 1988-10-13 | Shiseido Co Ltd | モノクロ−ナル抗体 |
| FR2614026B1 (fr) * | 1987-04-16 | 1992-04-17 | Sanofi Sa | Heparines de bas poids moleculaire, a structure reguliere, leur preparation et leurs applications biologiques |
| SE9002550D0 (sv) * | 1990-08-01 | 1990-08-01 | Kabivitrum Ab | Heparinfragment |
| SE9003181D0 (sv) | 1990-10-04 | 1990-10-04 | Kabivitrum Ab | Use of heparin fraction |
| US5250519A (en) | 1991-03-29 | 1993-10-05 | Glycomed Incorporated | Non-anticoagulant heparin derivatives |
| US5280016A (en) | 1991-03-29 | 1994-01-18 | Glycomed Incorporated | Non-anticoagulant heparin derivatives |
| JPH0532703A (ja) * | 1991-07-26 | 1993-02-09 | Terumo Corp | 低分子量ヘパリン誘導体の製造法 |
| AU5442594A (en) * | 1992-10-13 | 1994-05-09 | Virginia Commonwealth University | Use of non-anticoagulant heparin for treating ischemia/reperfusion injury |
| US5527785A (en) | 1993-05-14 | 1996-06-18 | The Regents Of The University Of California | Selectin receptor modulating compositions |
| US5744457A (en) * | 1995-03-31 | 1998-04-28 | Hamilton Civic Hospitals Research Development Inc. | Compositions and methods for inhibiting thrombogenesis |
| US5993810A (en) | 1996-03-15 | 1999-11-30 | Lebovitz; Shamir Israel | Method of softening or ripening the cervix of a female mammal using collagenase |
| WO1998016559A1 (fr) | 1996-10-15 | 1998-04-23 | Toray Industries, Inc. | Agent de maturation des canaux cervicaux |
| GB9711443D0 (en) * | 1997-06-03 | 1997-07-30 | Leo Pharm Prod Ltd | Chemical suppositions |
| JP3342007B2 (ja) * | 1997-11-20 | 2002-11-05 | 郁男 山科 | 低分子ヘパリン修飾体及び皮膚潰瘍治療剤 |
| US6596705B1 (en) | 1998-02-09 | 2003-07-22 | The Regents Of The University Of California | Inhibition of L-selectin and P-selection mediated binding using heparin |
| US6498246B1 (en) | 1998-02-26 | 2002-12-24 | Seikagaku Corporation | Glycosaminoglycan derivatives and processes for preparing same |
| US6028061A (en) | 1998-06-18 | 2000-02-22 | Children's Medical Center Corp | Angiogenesis inhibitors and use thereof |
| EP1022289B1 (en) * | 1998-07-31 | 2004-07-07 | Seikagaku Corporation | Novel glycosaminoglycan and drug compositions containing the same |
| JP2002523522A (ja) * | 1998-08-26 | 2002-07-30 | ザ コラボレイティブ グループ,リミテッド. | 非誘導化水溶性ベータ−(1,3)−グルカンのレセプター |
| MXPA02000142A (es) * | 1999-06-30 | 2003-07-21 | Hamilton Civic Hospitals Res | Composiciones de heparina que inhiben los factores de coagulacion asociados con el coagulo. |
| 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 |
| IT1316986B1 (it) | 2000-01-25 | 2003-05-26 | Sigma Tau Ind Farmaceuti | Derivati glicosamminoglicani parzialmente desolfatati nonanticoagulanti ad attivita' antiangiogenica. |
| 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 |
| DK1319183T3 (da) * | 2000-09-12 | 2009-05-18 | Massachusetts Inst Technology | Fremgangsmåder og produkter relateret til heparin med lav molekylvægt |
| SE521676C2 (sv) | 2002-01-02 | 2003-11-25 | Dilafor Ab | Användning av glykosaminoglykaner för prevention och behandling av värksvaghet vid fullgången graviditet |
| US20040072796A1 (en) | 2002-04-18 | 2004-04-15 | Embury Stephen H. | Method and composition for preventing pain in sickle cell patients |
| US8071569B2 (en) | 2002-09-20 | 2011-12-06 | Mousa Shaker A | Oxidized heparin fractions and their use in inhibiting angiogenesis |
| JP2005106694A (ja) * | 2003-09-30 | 2005-04-21 | Mochida Pharmaceut Co Ltd | 敗血症早期検出及び重篤度評価 |
| EP1582531A1 (en) | 2004-03-24 | 2005-10-05 | Aventis Pharma S.A. | Process for oxidizing unfractionated heparins and detecting presence or absence of glycoserine in heparin and heparin products |
| US20060040896A1 (en) * | 2004-08-18 | 2006-02-23 | Paringenix, Inc. | Method and medicament for anticoagulation using a sulfated polysaccharide with enhanced anti-inflammatory activity |
| US7741311B2 (en) | 2005-01-03 | 2010-06-22 | Shaker Mousa | Composition and method for treating occlusive vascular diseases, nerve regeneration, and wound healing |
| MX2008000974A (es) * | 2005-07-22 | 2008-03-27 | Univ California | Composiciones de heparina e inhibicion de selectina. |
| WO2007014155A2 (en) | 2005-07-22 | 2007-02-01 | Trf Pharma, Inc. | Method for treating sickle cell disease and sickle cell disease sequelae |
| AU2007233320B2 (en) * | 2006-04-04 | 2013-12-12 | Singulex, Inc. | Highly sensitive system and methods for analysis of troponin |
| CN101495517B (zh) * | 2006-05-25 | 2012-10-10 | 莫曼塔医药品有限公司 | 低分子量肝素及其用途 |
| EP2205642B1 (en) | 2007-11-02 | 2016-01-27 | Momenta Pharmaceuticals, Inc. | Non-anticoagulant polysaccharide compositions |
| US8592393B2 (en) * | 2007-11-02 | 2013-11-26 | Momenta Pharmaceuticals, Inc. | Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization |
| US8569262B2 (en) | 2007-11-02 | 2013-10-29 | Momenta Pharmaceuticals, Inc. | Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization |
| US8445436B2 (en) | 2007-12-03 | 2013-05-21 | Florida State University Research Foundation, Inc. | Oxytocin and melatonin compositions and associated methods for inducing labor |
| CN102177180A (zh) | 2008-04-04 | 2011-09-07 | 犹他州大学研究基金会 | 烷基化半合成的糖胺聚糖醚及其制备和使用方法 |
| WO2010111570A1 (en) * | 2009-03-27 | 2010-09-30 | E. I. Du Pont De Nemours And Company | Polyglycerol aldehydes |
| EP2419736B1 (en) | 2009-04-16 | 2014-01-29 | Momenta Pharmaceuticals, Inc. | Methods of assessing activity of a polysaccharide composition |
| US20120108538A1 (en) | 2009-06-30 | 2012-05-03 | James Beeson | Sulfated polysaccharides having antiplasmodial activity and methods and products for identifying antiplasmodial activity |
| CA2769258A1 (en) * | 2009-07-31 | 2011-02-03 | Bayer Healthcare Llc | Modified factor ix polypeptides and uses thereof |
| BR112012015029A2 (pt) * | 2009-12-22 | 2017-06-27 | Lifebond Ltd | matriz reticulada, método para controlar a formação de uma matriz, método ou matriz, método para vedar um tecido contra vazamento de um fluído corporal, agente hemostático ou vedante cirúrgico, composição para vedar um ferimento, uso da composição, composição para um veículo para entrega localizada de fármaco, composição para engenharia de tecido, e método para modificar uma composição |
| WO2013095215A1 (en) | 2011-12-19 | 2013-06-27 | Dilaforette Ab | Low anticoagulant heparins |
| CN104244957B (zh) | 2012-03-26 | 2017-11-17 | 迪乐方有限责任公司 | 用于治疗分娩停止的方法 |
| EP2830635A4 (en) | 2012-03-26 | 2016-03-16 | Dilafor Ab | COMBINATION TREATMENT OF ILLUSTRATED SULFATED GLYCOSAMINOGLYCANES |
-
2012
- 2012-12-19 ES ES12858809.2T patent/ES2656613T3/es active Active
- 2012-12-19 HU HUE12858809A patent/HUE036523T2/hu unknown
- 2012-12-19 PT PT128588092T patent/PT2794665T/pt unknown
- 2012-12-19 JP JP2014547146A patent/JP6543467B2/ja active Active
- 2012-12-19 DK DK12858809.2T patent/DK2794665T3/da active
- 2012-12-19 LT LTEP12858809.2T patent/LT2794665T/lt unknown
- 2012-12-19 AU AU2012354229A patent/AU2012354229B2/en active Active
- 2012-12-19 PL PL12858809T patent/PL2794665T3/pl unknown
- 2012-12-19 CN CN201280062050.1A patent/CN104144950B/zh active Active
- 2012-12-19 HR HRP20180124TT patent/HRP20180124T1/hr unknown
- 2012-12-19 SM SM20180143T patent/SMT201800143T1/it unknown
- 2012-12-19 RS RS20180155A patent/RS56874B1/sr unknown
- 2012-12-19 KR KR1020147016676A patent/KR102135485B1/ko active Active
- 2012-12-19 US US14/366,624 patent/US9475888B2/en active Active
- 2012-12-19 RU RU2014129816A patent/RU2617764C2/ru active
- 2012-12-19 MX MX2014007122A patent/MX351104B/es active IP Right Grant
- 2012-12-19 ME MEP-2018-14A patent/ME02994B/me unknown
- 2012-12-19 SI SI201231138T patent/SI2794665T1/en unknown
- 2012-12-19 CA CA2856492A patent/CA2856492C/en active Active
- 2012-12-19 WO PCT/SE2012/051433 patent/WO2013095279A1/en not_active Ceased
- 2012-12-19 EP EP12858809.2A patent/EP2794665B1/en active Active
- 2012-12-19 BR BR112014014454-0A patent/BR112014014454B1/pt active IP Right Grant
-
2013
- 2013-09-27 NO NO13771071A patent/NO2904345T3/no unknown
-
2014
- 2014-05-20 ZA ZA2014/03640A patent/ZA201403640B/en unknown
- 2014-06-01 IL IL232905A patent/IL232905A/en active IP Right Grant
- 2014-06-16 CO CO14129964A patent/CO7061069A2/es unknown
- 2014-06-19 CL CL2014001651A patent/CL2014001651A1/es unknown
-
2018
- 2018-02-09 CY CY20181100162T patent/CY1119899T1/el unknown
- 2018-02-28 JP JP2018034714A patent/JP2018111825A/ja active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0735050A2 (en) * | 1995-03-31 | 1996-10-02 | Hamilton Civic Hospitals Research Development, Inc. | Compositions for inhibiting thrombogenesis |
| US5767269A (en) * | 1996-10-01 | 1998-06-16 | Hamilton Civic Hospitals Research Development Inc. | Processes for the preparation of low-affinity, low molecular weight heparins useful as antithrombotics |
| WO2009007224A1 (en) * | 2007-07-10 | 2009-01-15 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Low molecular weight heparin derivatives having neuroprotective activity |
| RU2010122324A (ru) * | 2007-11-02 | 2011-12-10 | Момента Фармасьютикалз, Инк. (Us) | Полисахаридные композиции, не обладающие антикоагулянтными свойствами |
Non-Patent Citations (2)
| Title |
|---|
| "Inhibitor of slit protein interactions with the heparan sulphate proteoglycan glypican-1: Potential agents for the treatment of spinal cord injury" Lau, E., Margolis, R.U., 2010, Clinical and Experimental Pharmacology and Physiology 37 (4), pp. 417-421. "Does low molecular weight heparin shorten term labor? Ekman-Ordeberg, G., Akerud A., Dubicke, A., Malmström, A., Hellgren, M., 2010 Acta obstetricia et gynecologica Scandinavica 89 (1), pp. 147-150. * |
| "Inhibitor of slit protein interactions with the heparan sulphate proteoglycan glypican-1: Potential agents for the treatment of spinal cord injury" Lau, E., Margolis, R.U., 2010, Clinical and Experimental Pharmacology and Physiology 37 (4), pp. 417-421. "Does low molecular weight heparin shorten term labor? Ekman-Ordeberg, G., Akerud A., Dubicke, A., Malmström, A., Hellgren, M., 2010 Acta obstetricia et gynecologica Scandinavica 89 (1), pp. 147-150. * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2617764C2 (ru) | Неантикоагулянтные гликозаминогликаны, содержащие повторяющиеся дисахаридные звенья, и их медицинское применение | |
| EP2794666B1 (en) | Use of chemically modified heparin derivates in sickle cell disease | |
| US20150057226A1 (en) | Method for treatment of labor arrest | |
| EP3010940B1 (en) | New processes for the production of chemically-modified heparins | |
| US20150099703A1 (en) | Treatment of postpartum haemorrhage with chemically modified heparin or heparan sulphate and a uterotonic agent | |
| US20200254003A1 (en) | Oligosaccharide compound for inhibiting intrinsic coagulation factor x-enzyme complex, and preparation method therefor and uses thereof | |
| HK1202883B (en) | Non anti-coagulative glycosaminoglycans comprising repeating disaccharide unit and their medical use | |
| CN118459618A (zh) | 一种新型的半乳糖基化糖胺聚糖及其制备方法和用途 | |
| HK1220475B (en) | New processes for the production of chemically-modified heparins | |
| HK1199893B (en) | Use of chemically modified heparin derivates in sickle cell disease |