CA2281602A1 - Cross-linked vinyl polymers with bile acid adsorbing effect - Google Patents
Cross-linked vinyl polymers with bile acid adsorbing effect Download PDFInfo
- Publication number
- CA2281602A1 CA2281602A1 CA002281602A CA2281602A CA2281602A1 CA 2281602 A1 CA2281602 A1 CA 2281602A1 CA 002281602 A CA002281602 A CA 002281602A CA 2281602 A CA2281602 A CA 2281602A CA 2281602 A1 CA2281602 A1 CA 2281602A1
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- Prior art keywords
- another
- independently
- mixture
- mmol
- stirred
- 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
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- 239000003613 bile acid Substances 0.000 title claims description 41
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 title claims description 27
- 229920002554 vinyl polymer Polymers 0.000 title claims description 5
- 230000000694 effects Effects 0.000 title description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 77
- 229920000642 polymer Polymers 0.000 claims abstract description 71
- 150000001875 compounds Chemical class 0.000 claims abstract description 48
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 150000001450 anions Chemical class 0.000 claims abstract description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 5
- 239000002253 acid Substances 0.000 claims abstract description 4
- 125000006545 (C1-C9) alkyl group Chemical group 0.000 claims abstract 6
- 239000000203 mixture Substances 0.000 claims description 138
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 63
- 239000000178 monomer Substances 0.000 claims description 31
- 239000003999 initiator Substances 0.000 claims description 30
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 9
- 238000001179 sorption measurement Methods 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 230000009467 reduction Effects 0.000 claims description 7
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 6
- 241001484259 Lacuna Species 0.000 claims description 6
- 210000004369 blood Anatomy 0.000 claims description 6
- 239000008280 blood Substances 0.000 claims description 6
- 125000002348 vinylic group Chemical group 0.000 claims description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 5
- 150000004820 halides Chemical class 0.000 claims description 5
- 229920006037 cross link polymer Polymers 0.000 claims description 4
- 238000006845 Michael addition reaction Methods 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 230000001315 anti-hyperlipaemic effect Effects 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims description 2
- 230000037356 lipid metabolism Effects 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- 125000005843 halogen group Chemical group 0.000 claims 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- 238000007348 radical reaction Methods 0.000 claims 1
- 239000003524 antilipemic agent Substances 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 110
- 239000000243 solution Substances 0.000 description 101
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 99
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 97
- 229910052757 nitrogen Inorganic materials 0.000 description 92
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 91
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 75
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 54
- 239000000047 product Substances 0.000 description 53
- LBSPZZSGTIBOFG-UHFFFAOYSA-N bis[2-(4,5-dihydro-1h-imidazol-2-yl)propan-2-yl]diazene;dihydrochloride Chemical compound Cl.Cl.N=1CCNC=1C(C)(C)N=NC(C)(C)C1=NCCN1 LBSPZZSGTIBOFG-UHFFFAOYSA-N 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 229920006395 saturated elastomer Polymers 0.000 description 35
- 238000003756 stirring Methods 0.000 description 34
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 30
- 238000000108 ultra-filtration Methods 0.000 description 25
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 238000005342 ion exchange Methods 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 238000006116 polymerization reaction Methods 0.000 description 21
- 239000002244 precipitate Substances 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 19
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
- 239000000499 gel Substances 0.000 description 19
- 238000004809 thin layer chromatography Methods 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 235000012000 cholesterol Nutrition 0.000 description 17
- 238000000921 elemental analysis Methods 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- 239000006228 supernatant Substances 0.000 description 17
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000012071 phase Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- 239000012528 membrane Substances 0.000 description 12
- 239000003505 polymerization initiator Substances 0.000 description 12
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 11
- 238000004821 distillation Methods 0.000 description 11
- 210000004185 liver Anatomy 0.000 description 11
- 239000012465 retentate Substances 0.000 description 11
- 229920001268 Cholestyramine Polymers 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- WBWWGRHZICKQGZ-HZAMXZRMSA-N taurocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 WBWWGRHZICKQGZ-HZAMXZRMSA-N 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 210000000936 intestine Anatomy 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 239000012266 salt solution Substances 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- FLCAEMBIQVZWIF-UHFFFAOYSA-N 6-(dimethylamino)-2-methylhex-2-enamide Chemical compound CN(C)CCCC=C(C)C(N)=O FLCAEMBIQVZWIF-UHFFFAOYSA-N 0.000 description 6
- GDFCSMCGLZFNFY-UHFFFAOYSA-N Dimethylaminopropyl Methacrylamide Chemical compound CN(C)CCCNC(=O)C(C)=C GDFCSMCGLZFNFY-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000009102 absorption Effects 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 150000001336 alkenes Chemical class 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 210000001589 microsome Anatomy 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000012466 permeate Substances 0.000 description 6
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000012086 standard solution Substances 0.000 description 6
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- ZJJATABWMGVVRZ-UHFFFAOYSA-N 1,12-dibromododecane Chemical compound BrCCCCCCCCCCCCBr ZJJATABWMGVVRZ-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- 101100274389 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) chz-1 gene Proteins 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 229910052749 magnesium Inorganic materials 0.000 description 5
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- IUKIMAXMUXWYTA-UHFFFAOYSA-N 1-(bromomethyl)-4-[2-[4-(bromomethyl)phenyl]-1,1,1,3,3,3-hexafluoropropan-2-yl]benzene Chemical compound C=1C=C(CBr)C=CC=1C(C(F)(F)F)(C(F)(F)F)C1=CC=C(CBr)C=C1 IUKIMAXMUXWYTA-UHFFFAOYSA-N 0.000 description 4
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 4
- 239000005977 Ethylene Substances 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- -1 bile acid anions Chemical class 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000003795 desorption Methods 0.000 description 4
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 4
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 4
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 4
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 4
- 230000010235 enterohepatic circulation Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- RFDAIACWWDREDC-FRVQLJSFSA-N glycocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 RFDAIACWWDREDC-FRVQLJSFSA-N 0.000 description 4
- CBFCDTFDPHXCNY-UHFFFAOYSA-N icosane Chemical compound CCCCCCCCCCCCCCCCCCCC CBFCDTFDPHXCNY-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 4
- BGHCVCJVXZWKCC-UHFFFAOYSA-N tetradecane Chemical compound CCCCCCCCCCCCCC BGHCVCJVXZWKCC-UHFFFAOYSA-N 0.000 description 4
- 238000001291 vacuum drying Methods 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 3
- SAWCWRKKWROPRB-UHFFFAOYSA-N 1,1-dibromohexane Chemical compound CCCCCC(Br)Br SAWCWRKKWROPRB-UHFFFAOYSA-N 0.000 description 3
- STBMZSJLFYGOJU-UHFFFAOYSA-N 1,1-dibromooctane Chemical compound CCCCCCCC(Br)Br STBMZSJLFYGOJU-UHFFFAOYSA-N 0.000 description 3
- SGRHVVLXEBNBDV-UHFFFAOYSA-N 1,6-dibromohexane Chemical compound BrCCCCCCBr SGRHVVLXEBNBDV-UHFFFAOYSA-N 0.000 description 3
- DPBJAVGHACCNRL-UHFFFAOYSA-N 2-(dimethylamino)ethyl prop-2-enoate Chemical compound CN(C)CCOC(=O)C=C DPBJAVGHACCNRL-UHFFFAOYSA-N 0.000 description 3
- OYXZMSRRJOYLLO-AWBHSAGMSA-N 7a-hydroxycholesterol Chemical compound C([C@H]1O)=C2C[C@@H](O)CC[C@]2(C)[C@@H]2C1[C@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 OYXZMSRRJOYLLO-AWBHSAGMSA-N 0.000 description 3
- PZASAAIJIFDWSB-CKPDSHCKSA-N 8-[(1S)-1-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalen-2-yl]ethyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid Chemical compound FC(F)(F)C=1C2=CC([C@@H](N3C4CCC3CC(C4)C(O)=O)C)=CC=C2C=CC=1OC1CCC(C(F)(F)F)CC1 PZASAAIJIFDWSB-CKPDSHCKSA-N 0.000 description 3
- 239000004380 Cholic acid Substances 0.000 description 3
- 108010007979 Glycocholic Acid Proteins 0.000 description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 229960002471 cholic acid Drugs 0.000 description 3
- 235000019416 cholic acid Nutrition 0.000 description 3
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 3
- 229910000397 disodium phosphate Inorganic materials 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 3
- QYZFTMMPKCOTAN-UHFFFAOYSA-N n-[2-(2-hydroxyethylamino)ethyl]-2-[[1-[2-(2-hydroxyethylamino)ethylamino]-2-methyl-1-oxopropan-2-yl]diazenyl]-2-methylpropanamide Chemical compound OCCNCCNC(=O)C(C)(C)N=NC(C)(C)C(=O)NCCNCCO QYZFTMMPKCOTAN-UHFFFAOYSA-N 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 125000001453 quaternary ammonium group Chemical group 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 239000011775 sodium fluoride Substances 0.000 description 3
- 235000013024 sodium fluoride Nutrition 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 239000012089 stop solution Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- POOSGDOYLQNASK-UHFFFAOYSA-N tetracosan acid Natural products CCCCCCCCCCCCCCCCCCCCCCCC POOSGDOYLQNASK-UHFFFAOYSA-N 0.000 description 3
- LCUQJELQVHGIJS-UHFFFAOYSA-N 1,1-dibromododecane Chemical compound CCCCCCCCCCCC(Br)Br LCUQJELQVHGIJS-UHFFFAOYSA-N 0.000 description 2
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- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
- C08F8/44—Preparation of metal salts or ammonium salts
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F271/00—Macromolecular compounds obtained by polymerising monomers on to polymers of nitrogen-containing monomers as defined in group C08F26/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
-
- 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
- A61P3/06—Antihyperlipidemics
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- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F20/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
- C08F20/02—Monocarboxylic acids having less than ten carbon atoms, Derivatives thereof
- C08F20/10—Esters
- C08F20/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate
- C08F20/36—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate containing oxygen in addition to the carboxy oxygen, e.g. 2-N-morpholinoethyl (meth)acrylate or 2-isocyanatoethyl (meth)acrylate
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F22/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides or nitriles thereof
- C08F22/10—Esters
- C08F22/1006—Esters of polyhydric alcohols or polyhydric phenols, e.g. ethylene glycol dimethacrylate
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F22/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides or nitriles thereof
- C08F22/36—Amides or imides
- C08F22/38—Amides
- C08F22/385—Monomers containing two or more (meth)acrylamide groups, e.g. N,N'-methylenebisacrylamide
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Polymers & Plastics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19705963A DE19705963A1 (de) | 1997-02-17 | 1997-02-17 | Vernetzte Vinylpolymere mit Gallensäure-Adsorberwirkung |
| DE19705963.5 | 1997-02-17 | ||
| PCT/EP1998/000898 WO1998036002A1 (de) | 1997-02-17 | 1998-02-17 | Vernetzte vinylpolymere mit gallensäure-adsorberwirkung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2281602A1 true CA2281602A1 (en) | 1998-08-20 |
Family
ID=7820445
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002281602A Abandoned CA2281602A1 (en) | 1997-02-17 | 1998-02-17 | Cross-linked vinyl polymers with bile acid adsorbing effect |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP0960141A1 (cs) |
| JP (1) | JP2002515930A (cs) |
| KR (1) | KR20000071167A (cs) |
| CN (1) | CN1251112A (cs) |
| AU (1) | AU728985B2 (cs) |
| BR (1) | BR9807408A (cs) |
| CA (1) | CA2281602A1 (cs) |
| CZ (1) | CZ293299A3 (cs) |
| DE (1) | DE19705963A1 (cs) |
| HU (1) | HUP0001012A3 (cs) |
| PL (1) | PL335106A1 (cs) |
| RU (1) | RU99119911A (cs) |
| TR (1) | TR199901978T2 (cs) |
| WO (1) | WO1998036002A1 (cs) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7291673B2 (en) | 2000-06-02 | 2007-11-06 | Eidgenossiche Technische Hochschule Zurich | Conjugate addition reactions for the controlled delivery of pharmaceutically active compounds |
| US7413739B2 (en) | 1999-02-01 | 2008-08-19 | Eidgenossische Technische Hochschule Zurich | Conjugate addition reactions for the controlled delivery of pharmaceutically active compounds |
| US7744912B1 (en) | 1999-02-01 | 2010-06-29 | Eidgenossische Technische Hochschule Zurich | Biomaterials formed by nucleophilic addition reaction to conjugated unsaturated groups |
| US8282912B2 (en) | 2002-03-22 | 2012-10-09 | Kuros Biosurgery, AG | Compositions for tissue augmentation |
| US8961947B2 (en) | 2007-04-13 | 2015-02-24 | Kuros Biosurgery Ag | Polymeric tissue sealant |
| US20220402872A1 (en) * | 2019-11-12 | 2022-12-22 | Universita' Degli Studi Di Trieste | Photopolymerizable antibacterial monomer |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU4369499A (en) * | 1998-06-30 | 2000-01-17 | Aventis Research & Technologies Gmbh & Co. Kg | Novel method for producing cross-linked vinyl polymers based on quaternary ammonium groups exhibiting a bile acid adsorbent effect |
| JP2005054145A (ja) * | 2003-08-07 | 2005-03-03 | Mitsubishi Gas Chem Co Inc | ガスバリア性（メタ）アクリレート樹脂硬化物および塗料、接着剤、フィルム |
| JP6126498B2 (ja) * | 2013-02-15 | 2017-05-10 | 富士フイルム株式会社 | 高分子機能性膜及びその製造方法 |
| JP6071957B2 (ja) * | 2014-03-07 | 2017-02-01 | 富士フイルム株式会社 | イオン交換性ポリマーおよびその製造方法、電解質膜およびその製造方法ならびにイオン交換性ポリマー製造用組成物 |
| WO2017038328A1 (ja) * | 2015-08-31 | 2017-03-09 | 富士フイルム株式会社 | イオン交換ポリマー、硬化性組成物、硬化物、部材、及び、装置 |
| WO2019054797A1 (ko) | 2017-09-15 | 2019-03-21 | 주식회사 엘지화학 | 중합성 조성물, 고분자 캡슐 및 이를 포함하는 섬유 유연제 조성물 |
| CN110317588A (zh) * | 2018-03-29 | 2019-10-11 | 中国石油化工股份有限公司 | 一种阳离子表面活性剂及其制备方法和起泡剂及其应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR206115A1 (es) * | 1973-06-11 | 1976-06-30 | Merck & Co Inc | Procedimiento para preparar un polimero lineal no ramificado y no reticulado |
| GB9123683D0 (en) * | 1991-11-07 | 1992-01-02 | Sandoz Ltd | Improvements in or relating to organic compounds |
| DE69307112T2 (de) * | 1992-07-06 | 1997-04-17 | Otsuka Kagaku Kk | Polymerisierbares monomer, polymere und verfahren zu seiner herstellung |
| DE59307535D1 (de) * | 1992-07-22 | 1997-11-20 | Hoechst Ag | Hydrophile Zentren aufweisende Polyvinylamin-Derivate, Verfahren zu ihrer Herstellung sowie die Verwendung der Verbindungen als Arzneimittel, Wirkstoffträger und Nahrungsmittelhilfsstoff |
| US5618530A (en) * | 1994-06-10 | 1997-04-08 | Geltex Pharmaceuticals, Inc. | Hydrophobic amine polymer sequestrant and method of cholesterol depletion |
| US5624963A (en) * | 1993-06-02 | 1997-04-29 | Geltex Pharmaceuticals, Inc. | Process for removing bile salts from a patient and compositions therefor |
-
1997
- 1997-02-17 DE DE19705963A patent/DE19705963A1/de not_active Withdrawn
-
1998
- 1998-02-17 HU HU0001012A patent/HUP0001012A3/hu unknown
- 1998-02-17 CZ CZ992932A patent/CZ293299A3/cs unknown
- 1998-02-17 CA CA002281602A patent/CA2281602A1/en not_active Abandoned
- 1998-02-17 TR TR1999/01978T patent/TR199901978T2/xx unknown
- 1998-02-17 CN CN98803685A patent/CN1251112A/zh active Pending
- 1998-02-17 JP JP53537598A patent/JP2002515930A/ja active Pending
- 1998-02-17 BR BR9807408-3A patent/BR9807408A/pt not_active Application Discontinuation
- 1998-02-17 AU AU64983/98A patent/AU728985B2/en not_active Ceased
- 1998-02-17 EP EP98910693A patent/EP0960141A1/de not_active Withdrawn
- 1998-02-17 WO PCT/EP1998/000898 patent/WO1998036002A1/de not_active Application Discontinuation
- 1998-02-17 RU RU99119911/04A patent/RU99119911A/ru not_active Application Discontinuation
- 1998-02-17 KR KR1019997007457A patent/KR20000071167A/ko not_active Withdrawn
- 1998-02-17 PL PL98335106A patent/PL335106A1/xx unknown
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7413739B2 (en) | 1999-02-01 | 2008-08-19 | Eidgenossische Technische Hochschule Zurich | Conjugate addition reactions for the controlled delivery of pharmaceutically active compounds |
| US7670605B2 (en) | 1999-02-01 | 2010-03-02 | Eidgenossische Technische Hochschule Zurich | Conjugate addition reactions for the controlled delivery of pharmaceutically active compounds |
| US7744912B1 (en) | 1999-02-01 | 2010-06-29 | Eidgenossische Technische Hochschule Zurich | Biomaterials formed by nucleophilic addition reaction to conjugated unsaturated groups |
| US7291673B2 (en) | 2000-06-02 | 2007-11-06 | Eidgenossiche Technische Hochschule Zurich | Conjugate addition reactions for the controlled delivery of pharmaceutically active compounds |
| US8282912B2 (en) | 2002-03-22 | 2012-10-09 | Kuros Biosurgery, AG | Compositions for tissue augmentation |
| US8961947B2 (en) | 2007-04-13 | 2015-02-24 | Kuros Biosurgery Ag | Polymeric tissue sealant |
| US9180222B2 (en) | 2007-04-13 | 2015-11-10 | Kuros Biosurgery Ag | Polymeric tissue sealant |
| US20220402872A1 (en) * | 2019-11-12 | 2022-12-22 | Universita' Degli Studi Di Trieste | Photopolymerizable antibacterial monomer |
Also Published As
| Publication number | Publication date |
|---|---|
| BR9807408A (pt) | 2000-03-14 |
| AU6498398A (en) | 1998-09-08 |
| PL335106A1 (en) | 2000-04-10 |
| CZ293299A3 (cs) | 1999-12-15 |
| AU728985B2 (en) | 2001-01-25 |
| EP0960141A1 (de) | 1999-12-01 |
| JP2002515930A (ja) | 2002-05-28 |
| HUP0001012A3 (en) | 2001-11-28 |
| CN1251112A (zh) | 2000-04-19 |
| TR199901978T2 (xx) | 2000-06-21 |
| HUP0001012A2 (hu) | 2000-09-28 |
| RU99119911A (ru) | 2001-06-27 |
| KR20000071167A (ko) | 2000-11-25 |
| WO1998036002A1 (de) | 1998-08-20 |
| DE19705963A1 (de) | 1998-08-20 |
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Legal Events
| Date | Code | Title | Description |
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| FZDE | Discontinued |