DE3689493T2 - Verfahren zur Herstellung von reinem natürlichen Heparansulfat und Dermatansulfat und ihre pharmazeutische Verwendung. - Google Patents
Verfahren zur Herstellung von reinem natürlichen Heparansulfat und Dermatansulfat und ihre pharmazeutische Verwendung.Info
- Publication number
 - DE3689493T2 DE3689493T2 DE86102963T DE3689493T DE3689493T2 DE 3689493 T2 DE3689493 T2 DE 3689493T2 DE 86102963 T DE86102963 T DE 86102963T DE 3689493 T DE3689493 T DE 3689493T DE 3689493 T2 DE3689493 T2 DE 3689493T2
 - Authority
 - DE
 - Germany
 - Prior art keywords
 - solution
 - weight
 - sulfate
 - concentration
 - heparan sulfate
 - 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.)
 - Expired - Fee Related
 
Links
- 229920002971 Heparan sulfate Polymers 0.000 title claims abstract description 50
 - 229920000045 Dermatan sulfate Polymers 0.000 title claims abstract description 48
 - 238000000034 method Methods 0.000 title claims abstract description 34
 - 230000008569 process Effects 0.000 title claims abstract description 24
 - AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 title claims description 46
 - 229940051593 dermatan sulfate Drugs 0.000 title claims description 46
 - 238000004519 manufacturing process Methods 0.000 title description 5
 - 239000000203 mixture Substances 0.000 claims abstract description 14
 - 102000016611 Proteoglycans Human genes 0.000 claims abstract description 9
 - 108010067787 Proteoglycans Proteins 0.000 claims abstract description 9
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 - 239000000243 solution Substances 0.000 claims description 47
 - CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 24
 - OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
 - 229920002683 Glycosaminoglycan Polymers 0.000 claims description 23
 - XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 23
 - FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 22
 - 239000000047 product Substances 0.000 claims description 21
 - 238000011282 treatment Methods 0.000 claims description 21
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 - 102000004169 proteins and genes Human genes 0.000 claims description 9
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 - ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 6
 - UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 6
 - 238000003379 elimination reaction Methods 0.000 claims description 5
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 - VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 4
 - AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 4
 - 239000000920 calcium hydroxide Substances 0.000 claims description 4
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 - YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 4
 - 238000000108 ultra-filtration Methods 0.000 claims description 4
 - CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 3
 - 150000001298 alcohols Chemical class 0.000 claims description 3
 - 150000001875 compounds Chemical class 0.000 claims description 3
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 - 239000012895 dilution Substances 0.000 claims description 3
 - SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 3
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 - 102000039446 nucleic acids Human genes 0.000 claims description 3
 - 108020004707 nucleic acids Proteins 0.000 claims description 3
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 - ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 claims description 3
 - 229940116357 potassium thiocyanate Drugs 0.000 claims description 3
 - 210000001557 animal structure Anatomy 0.000 claims description 2
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 - 230000000694 effects Effects 0.000 abstract description 17
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 - 108010074860 Factor Xa Proteins 0.000 abstract description 6
 - 229960005348 antithrombin iii Drugs 0.000 abstract description 6
 - 239000003527 fibrinolytic agent Substances 0.000 abstract description 4
 - QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 abstract description 3
 - 230000003213 activating effect Effects 0.000 abstract description 2
 - 230000007515 enzymatic degradation Effects 0.000 abstract description 2
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 - FPJHWYCPAOPVIV-VOZMEZHOSA-N (2R,3S,4R,5R,6R)-6-[(2R,3R,4R,5R,6R)-5-acetamido-2-(hydroxymethyl)-6-methoxy-3-sulfooxyoxan-4-yl]oxy-4,5-dihydroxy-3-methoxyoxane-2-carboxylic acid Chemical compound CO[C@@H]1O[C@H](CO)[C@H](OS(O)(=O)=O)[C@H](O[C@@H]2O[C@H]([C@@H](OC)[C@H](O)[C@H]2O)C(O)=O)[C@H]1NC(C)=O FPJHWYCPAOPVIV-VOZMEZHOSA-N 0.000 abstract 2
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 - UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 4
 - 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 4
 - 229920000669 heparin Polymers 0.000 description 4
 - 229960002897 heparin Drugs 0.000 description 4
 - OIPPWFOQEKKFEE-UHFFFAOYSA-N orcinol Chemical compound CC1=CC(O)=CC(O)=C1 OIPPWFOQEKKFEE-UHFFFAOYSA-N 0.000 description 4
 - 239000002244 precipitate Substances 0.000 description 4
 - 102000005686 Serum Globulins Human genes 0.000 description 3
 - 108010045362 Serum Globulins Proteins 0.000 description 3
 - HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
 - 230000001112 coagulating effect Effects 0.000 description 3
 - 230000015271 coagulation Effects 0.000 description 3
 - 238000005345 coagulation Methods 0.000 description 3
 - 230000009089 cytolysis Effects 0.000 description 3
 - 230000005764 inhibitory process Effects 0.000 description 3
 - 230000003993 interaction Effects 0.000 description 3
 - 239000007788 liquid Substances 0.000 description 3
 - 239000007858 starting material Substances 0.000 description 3
 - 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 2
 - MSWZFWKMSRAUBD-UHFFFAOYSA-N 2-Amino-2-Deoxy-Hexose Chemical compound NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
 - 108010049003 Fibrinogen Proteins 0.000 description 2
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 - 239000012491 analyte Substances 0.000 description 2
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 - 238000010438 heat treatment Methods 0.000 description 2
 - 239000012528 membrane Substances 0.000 description 2
 - 230000036470 plasma concentration Effects 0.000 description 2
 - 230000002265 prevention Effects 0.000 description 2
 - 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 2
 - 150000003242 quaternary ammonium salts Chemical class 0.000 description 2
 - 230000019635 sulfation Effects 0.000 description 2
 - 238000005670 sulfation reaction Methods 0.000 description 2
 - 239000000725 suspension Substances 0.000 description 2
 - 229960004072 thrombin Drugs 0.000 description 2
 - 201000002282 venous insufficiency Diseases 0.000 description 2
 - OEANUJAFZLQYOD-CXAZCLJRSA-N (2r,3s,4r,5r,6r)-6-[(2r,3r,4r,5r,6r)-5-acetamido-3-hydroxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl]oxy-4,5-dihydroxy-3-methoxyoxane-2-carboxylic acid Chemical group CC(=O)N[C@H]1[C@H](OC)O[C@H](CO)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](OC)[C@H](C(O)=O)O1 OEANUJAFZLQYOD-CXAZCLJRSA-N 0.000 description 1
 - 229920002567 Chondroitin Polymers 0.000 description 1
 - 102000004032 Heparin Cofactor II Human genes 0.000 description 1
 - 108090000481 Heparin Cofactor II Proteins 0.000 description 1
 - 241000124008 Mammalia Species 0.000 description 1
 - 241001465754 Metazoa Species 0.000 description 1
 - 206010056717 Varicophlebitis Diseases 0.000 description 1
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 - 102000003801 alpha-2-Antiplasmin Human genes 0.000 description 1
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 - DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 1
 - 230000000295 complement effect Effects 0.000 description 1
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 - 238000006731 degradation reaction Methods 0.000 description 1
 - 201000010099 disease Diseases 0.000 description 1
 - 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
 - 231100000673 dose–response relationship Toxicity 0.000 description 1
 - 150000004676 glycans Chemical class 0.000 description 1
 - 238000000892 gravimetry Methods 0.000 description 1
 - 230000023597 hemostasis Effects 0.000 description 1
 - 239000012535 impurity Substances 0.000 description 1
 - 238000001727 in vivo Methods 0.000 description 1
 - 238000009776 industrial production Methods 0.000 description 1
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 - 238000007918 intramuscular administration Methods 0.000 description 1
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 - 239000000463 material Substances 0.000 description 1
 - 206010062198 microangiopathy Diseases 0.000 description 1
 - 230000002107 myocardial effect Effects 0.000 description 1
 - 230000001590 oxidative effect Effects 0.000 description 1
 - 230000003285 pharmacodynamic effect Effects 0.000 description 1
 - 229920001282 polysaccharide Polymers 0.000 description 1
 - 239000005017 polysaccharide Substances 0.000 description 1
 - 230000003389 potentiating effect Effects 0.000 description 1
 - 235000004252 protein component Nutrition 0.000 description 1
 - 239000002689 soil Substances 0.000 description 1
 - 239000007787 solid Substances 0.000 description 1
 - UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical class [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
 - 201000005060 thrombophlebitis Diseases 0.000 description 1
 - 230000002792 vascular Effects 0.000 description 1
 
Classifications
- 
        
- C—CHEMISTRY; METALLURGY
 - C07—ORGANIC CHEMISTRY
 - C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
 - C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
 
 - 
        
- 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
 - C08B37/0066—Isolation or extraction of proteoglycans from organs
 
 - 
        
- 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
 
 - 
        
- 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
 - C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
 - C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
 - C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
 - C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; 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
 - C08B37/0069—Chondroitin-4-sulfate, i.e. chondroitin sulfate A; Dermatan sulfate, i.e. chondroitin sulfate B or beta-heparin; Chondroitin-6-sulfate, i.e. chondroitin sulfate C; Derivatives thereof
 
 
Landscapes
- Chemical & Material Sciences (AREA)
 - Health & Medical Sciences (AREA)
 - Life Sciences & Earth Sciences (AREA)
 - Organic Chemistry (AREA)
 - Engineering & Computer Science (AREA)
 - General Health & Medical Sciences (AREA)
 - Molecular Biology (AREA)
 - Biochemistry (AREA)
 - Chemical Kinetics & Catalysis (AREA)
 - Medicinal Chemistry (AREA)
 - Materials Engineering (AREA)
 - Polymers & Plastics (AREA)
 - Dermatology (AREA)
 - Diabetes (AREA)
 - Pharmacology & Pharmacy (AREA)
 - Bioinformatics & Cheminformatics (AREA)
 - Biotechnology (AREA)
 - Hematology (AREA)
 - General Chemical & Material Sciences (AREA)
 - Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
 - Genetics & Genomics (AREA)
 - Animal Behavior & Ethology (AREA)
 - Public Health (AREA)
 - Veterinary Medicine (AREA)
 - Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
 - Polysaccharides And Polysaccharide Derivatives (AREA)
 - Pyrane Compounds (AREA)
 - Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
 - Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
 - Preparation Of Compounds By Using Micro-Organisms (AREA)
 - Steroid Compounds (AREA)
 - Nitrogen Condensed Heterocyclic Rings (AREA)
 - Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
 - Saccharide Compounds (AREA)
 - Peptides Or Proteins (AREA)
 
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title | 
|---|---|---|---|
| IT8519885A IT1208509B (it) | 1985-03-13 | 1985-03-13 | Processo per la produzione di eparan solfato e dermatan solfato naturali sostanzialmente puri eloro impiego farmaceutico. | 
Publications (2)
| Publication Number | Publication Date | 
|---|---|
| DE3689493D1 DE3689493D1 (de) | 1994-02-17 | 
| DE3689493T2 true DE3689493T2 (de) | 1994-04-28 | 
Family
ID=11162062
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date | 
|---|---|---|---|
| DE86102963T Expired - Fee Related DE3689493T2 (de) | 1985-03-13 | 1986-03-06 | Verfahren zur Herstellung von reinem natürlichen Heparansulfat und Dermatansulfat und ihre pharmazeutische Verwendung. | 
Country Status (20)
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title | 
|---|---|---|---|---|
| IT1189085B (it) * | 1986-03-25 | 1988-01-28 | Mediolanum Farmaceutici Srl | Processo per la preparazione di dermatan solfato ad alta purezza e composizioni farmaceutiche che lo contengono | 
| US5707604A (en) * | 1986-11-18 | 1998-01-13 | Access Pharmaceuticals, Inc. | Vivo agents comprising metal-ion chelates with acidic saccharides and glycosaminoglycans, giving improved site-selective localization, uptake mechanism, sensitivity and kinetic-spatial profiles | 
| DE3639561A1 (de) * | 1986-11-20 | 1988-06-01 | Baumann Hanno | Verfahren zur herstellung von nicht-thrombogenen substraten | 
| IT1232939B (it) * | 1987-11-06 | 1992-03-10 | Opocrin Spa | Eparan solfato caratterizzato da elevata attivita' antitrombotica, elevata biodisponibilita', assenza di attivita' anticoagulante; suo processo di estrazione da organi e da tessuti e relative composizioni farmaceutiche | 
| JPH04500377A (ja) * | 1988-06-03 | 1992-01-23 | イタルファルマコ エッセ ピ ア | グリコサミノグリカン塩、その製造方法およびそれを含有する医薬組成物 | 
| ES2062307T3 (es) * | 1989-10-04 | 1994-12-16 | Akzo Nv | Un proceso para la fabricacion de glicosaminoglicuronano sulfatado con actividad antitrombotica. | 
| EP0493533A4 (en) * | 1989-10-27 | 1992-10-28 | Case Western Reserve University | Inhibition of cell growth by keratan sulfate, chondroitin sulfate, dermatan sulfate and other glycans | 
| IT1240615B (it) * | 1990-04-03 | 1993-12-17 | Mediolanum Farmaceutici Spa | Impiego del dermatan solfato nella prevenzione e terapia dell'invecchiamento cerebrale e degli stati di deficit funzionale del sistema nervoso centrale | 
| AU7742591A (en) * | 1990-04-06 | 1991-10-30 | Washington University | Anticoagulant oligosaccharides | 
| US5705178A (en) * | 1991-05-31 | 1998-01-06 | Gliatech, Inc. | Methods and compositions based on inhibition of cell invasion and fibrosis by anionic polymers | 
| US5605938A (en) * | 1991-05-31 | 1997-02-25 | Gliatech, Inc. | Methods and compositions for inhibition of cell invasion and fibrosis using dextran sulfate | 
| FR2691066B1 (fr) * | 1992-05-15 | 1995-06-09 | Sanofi Elf | Utilisation de glycosaminoglycanes exogenes, de leurs analogues ainsi que de leurs fragments, fractions et derives, pour la preparation de medicaments destines au traitement de thrombopenies. | 
| IT1256236B (it) * | 1992-12-23 | 1995-11-29 | Mediolanum Farmaceutici Srl | Oligosaccaridi aventi attivita' biologica e procedimento per la loro preparazione di glicosaminoglicani | 
| CN1115182A (zh) * | 1993-09-30 | 1996-01-17 | 生化学工业株式会社 | 抗血栓剂 | 
| US6106866A (en) * | 1995-07-31 | 2000-08-22 | Access Pharmaceuticals, Inc. | In vivo agents comprising cationic drugs, peptides and metal chelators with acidic saccharides and glycosaminoglycans, giving improved site-selective localization, uptake mechanism, sensitivity and kinetic-spatial profiles, including tumor sites | 
| IT1296581B1 (it) * | 1997-11-28 | 1999-07-14 | Istituto Scient Di Chimica E B | Materiali polimerici non trombogenici e ad esaltata compatibilita' con fluidi e tessuti organici | 
| EP1192187A1 (en) * | 1999-06-30 | 2002-04-03 | Hamilton Civic Hospitals Research Development, Inc. | Heparin compositions that inhibit clot associated coagulation factors | 
| CN1473061A (zh) * | 2000-09-08 | 2004-02-04 | ���ܶ�����ҽԺ�о���չ����˾ | 抗血栓形成的组合物 | 
| CN107098989A (zh) * | 2017-04-27 | 2017-08-29 | 甘肃省金羚集团药业有限公司 | 一种肝素钠的制备方法 | 
| CN114478832B (zh) * | 2022-02-14 | 2023-03-03 | 河北常山生化药业股份有限公司 | 从肝素钠副产物中提纯四种多糖类产品的方法 | 
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title | 
|---|---|---|---|---|
| US3179566A (en) * | 1963-05-16 | 1965-04-20 | Canada Packers Ltd | Purification of heparin | 
| JPS5318520B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1972-07-05 | 1978-06-15 | ||
| AR207237A1 (es) * | 1974-02-25 | 1976-09-22 | Thomas A | Procedimiento para obtener extractos biologicos estables liofilizados solubles constituidos por complejos proteicos termorresistentes | 
| US4243582A (en) * | 1979-04-26 | 1981-01-06 | Monsanto Company | Novel glycoproteins from bovine cartilage | 
| JPS58171403A (ja) * | 1982-04-01 | 1983-10-08 | Eisai Co Ltd | ヘパラン硫酸の精製法 | 
| IT1189298B (it) * | 1982-06-18 | 1988-02-04 | Manetti & Roberts Italo Brit | Procedimento per produrre i glicosa minoglicani dermatansolfato ed eparan-solfato sostanzialmente puri e loro impiego farmaceutico | 
| FR2555993B1 (fr) * | 1983-12-06 | 1986-11-07 | Anic Spa | Chitosanes 6-sulfates et procede pour leur preparation | 
| IT1195497B (it) * | 1983-03-08 | 1988-10-19 | Opocrin Spa | Procedimento per la preparazione di frazioni oligosaccaridiche dotate di proprieta' farmacologiche per degradazione chimica di eparina | 
| IT1163772B (it) * | 1983-07-13 | 1987-04-08 | Baldacci Lab Spa | Oligosaccaridi eterogenei complessabili ed alfa-idosani ad attivita' terapeutica, procedimento per la loro preparazione e relative composizioni farmaceutiche | 
- 
        1985
        
- 1985-03-13 IT IT8519885A patent/IT1208509B/it active
 
 - 
        1986
        
- 1986-03-06 DE DE86102963T patent/DE3689493T2/de not_active Expired - Fee Related
 - 1986-03-06 EP EP86102963A patent/EP0199033B1/en not_active Expired - Lifetime
 - 1986-03-06 AT AT86102963T patent/ATE99702T1/de not_active IP Right Cessation
 - 1986-03-10 US US06/838,133 patent/US4783447A/en not_active Expired - Fee Related
 - 1986-03-11 NZ NZ215435A patent/NZ215435A/xx unknown
 - 1986-03-12 FI FI861020A patent/FI82700C/fi not_active IP Right Cessation
 - 1986-03-12 IN IN184/CAL/86A patent/IN163616B/en unknown
 - 1986-03-12 DK DK113886A patent/DK113886A/da not_active Application Discontinuation
 - 1986-03-12 GR GR860677A patent/GR860677B/el unknown
 - 1986-03-12 ES ES552898A patent/ES8705894A1/es not_active Expired
 - 1986-03-12 NO NO860940A patent/NO166187C/no unknown
 - 1986-03-12 CA CA000503943A patent/CA1286286C/en not_active Expired - Lifetime
 - 1986-03-12 ZA ZA861855A patent/ZA861855B/xx unknown
 - 1986-03-12 PH PH33516A patent/PH22370A/en unknown
 - 1986-03-13 AU AU54727/86A patent/AU582221B2/en not_active Ceased
 - 1986-03-13 JP JP61053838A patent/JPS61218601A/ja active Granted
 - 1986-03-13 KR KR1019860001805A patent/KR910006809B1/ko not_active Expired
 - 1986-03-13 YU YU37586A patent/YU46303B/sh unknown
 - 1986-03-13 PT PT82198A patent/PT82198B/pt unknown
 
 - 
        1987
        
- 1987-06-10 PH PH35381A patent/PH25136A/en unknown
 
 
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