JPH0257580B2 - - Google Patents
Info
- Publication number
- JPH0257580B2 JPH0257580B2 JP56182728A JP18272881A JPH0257580B2 JP H0257580 B2 JPH0257580 B2 JP H0257580B2 JP 56182728 A JP56182728 A JP 56182728A JP 18272881 A JP18272881 A JP 18272881A JP H0257580 B2 JPH0257580 B2 JP H0257580B2
- Authority
- JP
- Japan
- Prior art keywords
- parts
- weight
- maleic anhydride
- carrier
- component
- 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 - Lifetime
Links
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 claims description 23
- 239000013543 active substance Substances 0.000 claims description 22
- 229920001577 copolymer Polymers 0.000 claims description 18
- 239000007795 chemical reaction product Substances 0.000 claims description 13
- 239000000178 monomer Substances 0.000 claims description 13
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 8
- FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 claims description 8
- 230000003100 immobilizing effect Effects 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 5
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
- 239000005977 Ethylene Substances 0.000 claims description 4
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- XJRBAMWJDBPFIM-UHFFFAOYSA-N methyl vinyl ether Chemical compound COC=C XJRBAMWJDBPFIM-UHFFFAOYSA-N 0.000 claims description 4
- FPSURBCYSCOZSE-UHFFFAOYSA-N 1-ethenoxybutan-1-ol Chemical compound CCCC(O)OC=C FPSURBCYSCOZSE-UHFFFAOYSA-N 0.000 claims description 3
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 claims description 3
- 125000000524 functional group Chemical group 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 3
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- 230000009257 reactivity Effects 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 239000000427 antigen Substances 0.000 description 13
- 108091007433 antigens Proteins 0.000 description 13
- 102000036639 antigens Human genes 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 239000000047 product Substances 0.000 description 11
- 239000007864 aqueous solution Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 9
- -1 Cephadex Substances 0.000 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
- UPBDXRPQPOWRKR-UHFFFAOYSA-N furan-2,5-dione;methoxyethene Chemical compound COC=C.O=C1OC(=O)C=C1 UPBDXRPQPOWRKR-UHFFFAOYSA-N 0.000 description 8
- 229920002451 polyvinyl alcohol Polymers 0.000 description 8
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000004372 Polyvinyl alcohol Substances 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 108010074605 gamma-Globulins Proteins 0.000 description 6
- 208000006454 hepatitis Diseases 0.000 description 6
- 231100000283 hepatitis Toxicity 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 5
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 229920000768 polyamine Polymers 0.000 description 5
- 229960005356 urokinase Drugs 0.000 description 5
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 239000003146 anticoagulant agent Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- JJCQSGDBDPYCEO-XVZSLQNASA-N dibekacin Chemical compound O1[C@H](CN)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N JJCQSGDBDPYCEO-XVZSLQNASA-N 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- 239000012730 sustained-release form Substances 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 229960004676 antithrombotic agent Drugs 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000011247 coating layer Substances 0.000 description 3
- 238000007334 copolymerization reaction Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical class CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000700721 Hepatitis B virus Species 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 108010093965 Polymyxin B Proteins 0.000 description 2
- 239000004721 Polyphenylene oxide Substances 0.000 description 2
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000001414 amino alcohols Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 2
- VHRGRCVQAFMJIZ-UHFFFAOYSA-N cadaverine Chemical compound NCCCCCN VHRGRCVQAFMJIZ-UHFFFAOYSA-N 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 239000000645 desinfectant Substances 0.000 description 2
- GYZLOYUZLJXAJU-UHFFFAOYSA-N diglycidyl ether Chemical class C1OC1COCC1CO1 GYZLOYUZLJXAJU-UHFFFAOYSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000578 dry spinning Methods 0.000 description 2
- 239000003527 fibrinolytic agent Substances 0.000 description 2
- 230000003480 fibrinolytic effect Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- QQVIHTHCMHWDBS-UHFFFAOYSA-N isophthalic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229920005615 natural polymer Polymers 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 229920006267 polyester film Polymers 0.000 description 2
- 229920000570 polyether Polymers 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 229920000024 polymyxin B Polymers 0.000 description 2
- 229960005266 polymyxin b Drugs 0.000 description 2
- 239000001294 propane Substances 0.000 description 2
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 2
- 238000009987 spinning Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- MTZUIIAIAKMWLI-UHFFFAOYSA-N 1,2-diisocyanatobenzene Chemical compound O=C=NC1=CC=CC=C1N=C=O MTZUIIAIAKMWLI-UHFFFAOYSA-N 0.000 description 1
- PGRNEGLBSNLPNP-UHFFFAOYSA-N 1,6-dichloro-3-methylhex-1-ene Chemical compound ClC=CC(C)CCCCl PGRNEGLBSNLPNP-UHFFFAOYSA-N 0.000 description 1
- PWGJDPKCLMLPJW-UHFFFAOYSA-N 1,8-diaminooctane Chemical compound NCCCCCCCCN PWGJDPKCLMLPJW-UHFFFAOYSA-N 0.000 description 1
- DBTNNHQROYDOOG-UHFFFAOYSA-N 1-(furan-2-yl)prop-2-en-1-one Chemical compound C=CC(=O)C1=CC=CO1 DBTNNHQROYDOOG-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
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- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- VVJIVFKAROPUOS-UHFFFAOYSA-N 2,2-bis(aminomethyl)propane-1,3-diamine Chemical compound NCC(CN)(CN)CN VVJIVFKAROPUOS-UHFFFAOYSA-N 0.000 description 1
- HJKLEAOXCZIMPI-UHFFFAOYSA-N 2,2-diethoxyethanamine Chemical class CCOC(CN)OCC HJKLEAOXCZIMPI-UHFFFAOYSA-N 0.000 description 1
- GHKSKVKCKMGRDU-UHFFFAOYSA-N 2-(3-aminopropylamino)ethanol Chemical compound NCCCNCCO GHKSKVKCKMGRDU-UHFFFAOYSA-N 0.000 description 1
- OZDGMOYKSFPLSE-UHFFFAOYSA-N 2-Methylaziridine Chemical compound CC1CN1 OZDGMOYKSFPLSE-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- AWFYPPSBLUWMFQ-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)ethanone Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=C2 AWFYPPSBLUWMFQ-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- ULGJWNIHLSLQPZ-UHFFFAOYSA-N 7-[(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-n-[2-(1h-indol-3-yl)ethyl]heptanamide Chemical compound C1CCCC2=NC3=CC(Cl)=CC(Cl)=C3C(NCCCCCCC(=O)NCCC=3C4=CC=CC=C4NC=3)=C21 ULGJWNIHLSLQPZ-UHFFFAOYSA-N 0.000 description 1
- IYLLULUTZPKQBW-UHFFFAOYSA-N Acrinol Chemical compound CC(O)C(O)=O.C1=C(N)C=CC2=C(N)C3=CC(OCC)=CC=C3N=C21 IYLLULUTZPKQBW-UHFFFAOYSA-N 0.000 description 1
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- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
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- 102000019040 Nuclear Antigens Human genes 0.000 description 1
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- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 108010034949 Thyroglobulin Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
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- GKXVJHDEWHKBFH-UHFFFAOYSA-N [2-(aminomethyl)phenyl]methanamine Chemical compound NCC1=CC=CC=C1CN GKXVJHDEWHKBFH-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
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Description
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é¢ãããã®ã§ãããDETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel carrier for immobilizing a physiologically active substance.
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ãã Conventionally, many attempts have been made to immobilize physiologically active substances on carriers to make them insoluble, thereby stabilizing or sustaining their activity or making them easier to use.
In such attempts, it is important to use an appropriate carrier in order to effectively exert the various activities of the physiologically active substance. The functions required of such a carrier are that it has a high ability to immobilize physiologically active substances, that the immobilization reaction does not require high temperatures to the extent that the activity of the physiologically active substance is lost, and that It is possible to release biologically active substances in a sustained manner or to permanently retain them on a carrier depending on the purpose, and the carrier itself is stable in the place where it is used. Examples include the ability to obtain molded products of various shapes such as granules, and the ability to provide a strong coating layer that can be coated on various molded products. However, among the various carriers currently in use, although some of them retain each of the above-mentioned functions, they do not satisfactorily retain all of them. For example, conventionally known typical carriers such as Cephadex, glass beads, and activated carbon have only been available in fixed shapes. It was impossible to obtain such information, and there were limits to where it could be used. In addition, polymers having maleic anhydride groups, such as copolymers of aromatic vinyl monomers and maleic anhydride or copolymers of aliphatic vinyl ether and maleic anhydride, can be used as carriers for immobilizing physiologically active substances. Although examples in which they have been used are known, it is difficult to use them alone due to problems such as stringability, formability such as film forming properties, and water resistance, and no such examples have been found. In addition, filamentous materials made of the reaction product of the former copolymer and a crosslinking agent are known from U.S. Pat. No. 3,966,839, U.S. Pat. has poor ability to immobilize physiologically active substances. Furthermore, a molded article made of a reaction product of the latter copolymer and a crosslinking agent is known from U.S. Pat. No. 3,810,468;
The molded product is hard but brittle, making it impossible to use it as a column filler, filter, etc. Further, in this case, if the crosslinking reaction is carried out sufficiently to satisfy the above-mentioned functions, the functions will be drastically reduced. Homopolymers obtained from monomers having acidic groups other than maleic anhydride, such as carboxyl groups, sulfone groups, phosphonic groups, phosphine groups, phenolic hydroxyl groups, etc., and copolymers with other monomers copolymerizable with these monomers. There are many reports using these as carriers, but when these are used as carriers, high temperatures are required for the immobilization reaction (i.e., they do not fulfill the function), and when immobilized at low temperatures, the period of time they remain on the carrier is limited. The number of acidic groups in the polymer is small compared to the molecular weight (i.e., the function is not satisfied), and there are many things that cannot be molded or coated (i.e., the functionality is not satisfied). It cannot be used satisfactorily for reasons such as:
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ã§ããã In view of these current circumstances, the present inventors have conducted intensive research in order to obtain a carrier that satisfies all of the functions as a carrier, and have found that (A) maleic anhydride and an aromatic vinyl monomer or The reaction product of an olefin monomer, (B) a copolymer of maleic anhydride and an aliphatic vinyl ether or aliphatic vinyl ester copolymerizable with it, and (C) a polyfunctional compound can be used as a carrier for immobilizing a physiologically active substance. The present invention has been developed based on the discovery that the method is superior.
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ãèŠæšãšããã That is, the present invention provides 0.5 to 99.5 parts by weight of (A) a copolymer of maleic anhydride and at least one monomer selected from the group consisting of styrene, ethylene, isobutylene, and propylene (hereinafter referred to as component (A)); , (B) a copolymer of maleic anhydride and at least one monomer selected from the group consisting of methyl vinyl ether, ethyl vinyl ether, butanediol vinyl ether, and vinyl acetate (hereinafter referred to as
(referred to as component (B)) 0.5 to 99.5 parts by weight, component (A) and (B)
1 to 200 parts by weight of (C) per 100 parts by weight of the total amount of ingredients
Component (A) is added to a compound containing two or more functional groups in one molecule that are reactive with a maleic anhydride group or a carboxyl group generated by hydrolysis of a maleic anhydride group (hereinafter referred to as component (C)). The gist of the present invention is a carrier for immobilizing a physiologically active substance, which is made of a reaction product obtained by reacting component (B) with component (B).
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ã¯ããã«åªããŠãããšããäºå®ã§ããã The carrier of the present invention is an excellent carrier that can satisfy all of the above-mentioned functions required for a carrier for immobilizing a physiologically active substance, but what is particularly noteworthy is that component (A)
The ability of the carrier of the present invention comprising a reaction product of component (B) and component (C) to immobilize a physiologically active substance is determined by the reaction product of component (A) and component (C); The fact is that the performance is far superior to that expected when the reaction product of the component and (C) component is mixed.
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ããŒã«ãªHBsæäœãªã©ãçšããããã The term "physiologically active substance" as used in the present invention refers to a substance that has some pharmacological effect or physiological influence on living organisms, such as antigens and antibodies against them, hormones and receptors against them, enzymes and their substrates, inhibitors, and complements. Related substances such as enzymes, various blood proteins, drugs such as antibiotics and disinfectants,
Examples include antithrombotic agents. More specifically, for example, antigens extracted from the glomerular basement membrane of the kidney,
Antigens such as nuclear antigens and proteinaceous antigens in body fluids, B
Antibodies against hepatitis surfactant antigen ( HBs antibody), l antibodies, antibodies against angiotensin,
Antibodies such as antibodies against cortisol, complements such as the g component of C complement, hormones, receptors for hormones, deoxyribonuclease, amylase, trypsin, chymotrypsin, aminoacylase, galactosidase, invertase, pectinase, L-asparaginase, glucose oxidase, Enzymes such as uriase and cellulase, substrates for enzymes, enzyme inhibitors such as aprotinin, blood proteins such as albumin, globulin, ceruloplasmin, transferrin, thyroglobulin, haptoglobin, hemopexin, conglutinin, amikacin, dipekacin,
Antibiotics such as kanamycin, streptomycin, gentamicin, fradiomycin, polymyxin, disinfectants such as acrinol, acrylfuran, benzalkonium chloride, benzethonium chloride, cyclohexidine, streptokinase, urokinase, plasmin, purinase, synthetic fibrinolytic activators, etc. Examples include fibrinolytic activators, anticoagulants such as heparin and coumarin derivatives, and antithrombotic agents such as platelet inhibitors such as dipyridamole, but in the present invention, various enzymes, antigens, antibodies, antibiotics, bactericidal agents, etc. is preferably used. In particular, HBs antibodies are preferably used as antibodies, and HBs antibodies in human blood, purified HBs antigens or HBs antibodies recovered from antiserum obtained by immunizing humans or animals with vaccines, and HBs antibodies by cell fusion can be used. Monoclonal HBs antibodies, etc., obtained by this method are used.
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䜿çšãããã As component (A) in the present invention, a copolymer of maleic anhydride and at least one monomer selected from the group consisting of styrene, ethylene, isobutylene, and propylene is used. Polymerization ratio is 1:1 to 1:5
and those having a molecular weight of 500 to 2,000,000 are preferably used.
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1:5 and a molecular weight of 500 to 2,000,000 is preferably used.
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ïŒEncyclopedia of Polymer Science and
TechnologyïŒ10å·»ã616é ãã(ii)ãšãã¬ã³ã€ãã³ã
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ã«ã¢ãã³ãçšããããã Furthermore, as component (C) in the present invention, a compound containing two or more functional groups in one molecule that is reactive with a maleic anhydride group or a carboxyl group generated by hydrolysis of a maleic anhydride group is used. used. Examples of such compounds include polyisocyanates such as hexamethylene diisocyanate, toluene diisocyanate, xylene diisocyanate, phenylene diisocyanate, isocyanate derivatives of aniline-formaldehyde, tetramethylene glycol, glycidyl ethers, etc. , polyeposides such as diglycidyl ether of diethylene glycol, polyvinyl alcohol, copolymers of polyvinyl alcohol with ethylene, propylene, vinyl chloride, allyl alcohol, N-vinylpyrrolidone, etc., methyl, ethyl, propyl, butyl, octyl of polyvinyl alcohol, Ether derivatives such as dodecyl and phenyl, formal of polyvinyl alcohol, acetal derivatives such as ethanal, butyral, and aminoacetal, ester derivatives of polyvinyl alcohol such as acetic acid, formic acid, butyric acid, caproic acid, lauric acid, stearic acid, and benzoic acid, ethylene Glycol, propylene glycol, butylene glycol, diethylene glycol, cyclohexanediol, pentaerythritol, glycerin,
Polyols such as 1,1,1-trimethylolpropane and their carboxymethylated products, polyether polyols such as polyethylene glycol, polypropylene glycol, polytetramethylene glycol and their carboxymethylated products, succinic acid, glutaric acid, adipic acid, sebacic acid,
Polyesters having hydroxyl groups at both ends obtained by condensing dicarboxylic acids such as isophthalic acid, phthalic acid, and terephthalic acid with glycols such as ethylene glycol, propylene glycol, butylene glycol, and their carboxymethylated products, starch, gelatin, and dextran. Examples include natural polymers such as and their carboxymethylated products, amino alcohols such as monoethanolamine and triethanolamine, and polyamines. Examples of polyamines include low-molecular polyamines such as ethylenediamine, trimethylenediamine, 1,2-diaminopropane, tetramethylenediamine, 1,3-diaminobutane, 2,3
-diaminobutane, pentamethylenediamine,
2,4-diaminopentane, hexamethylenediamine, octamethylenediamine, nonamethylenediamine, decamethylenediamine, undecamethylenediamine, dodecamethylenediamine, tridecamethylenediamine, octadecamethylenediamine, N,N-dimethylethylenediamine, N ,N
-diethyltrimethylenediamine, N,N-dimethyltrimethylenediamine, N,N-dibutyltrimethylenediamine, N,N,N'-triethylethylenediamine, N-methyltrimethylenediamine, N,N-dimethyl-p-phene Nylenediamine, N,N-dimethylhexamethylenediamine,
Diethylenetriamine, triethylenethitramine, tetraethylenepentamine, heptaethyleneoctamine, nonaethylenedecamine, 1,3-bis(2'-aminoethylamino)propane, bis(3-aminopropal)amine, 1,3 -bis(3'-aminopropylamino)propane, 1,2,
3-triaminopropane, tris(2-aminoethyl)amine, tetra(aminomethyl)methane,
Methyliminobispropylamine, methyliminobisethylamine, ethyliminobisethylamine, N-aminopropyl-2morpholine, N-aminopropyl-2-pipecoline, N-(2-hydroxyethyl)trimethylenediamine, xylylenediamine, nylenediamine, piperazine,
N-methylpiperazine, N-(2-aminoethyl)
Examples include ethanolamine, N-aminoethylpiperazine, N,N,N'-tetramethylethylenediamine, N,N,N',N'-tetramethyltetramethylenediamine, and polymeric polyamines such as (i) amines and alkylenes. Poly(allene polyamine) synthesized from dihalite or epichlorohydrin [encyclopidio of
Polymer Science and Technology,
(Encyclopedia of Polymer Science and
Technology) Volume 10, Page 616], (ii) Ethyleneimine,
Alkylene imine polymers obtained by ring-opening polymerization of alkylene imines such as propylene imine [Encyclopedia of Polymer Science and Technology, vol. 1, p. 734],
(iii) Others include polyvinylamine, polylysine, etc. Among these, polyvinyl alcohol and its derivatives, polyols, polyether polyols, natural polymers, and amino alcohols are preferably used, and particularly preferably polyvinyl alcohols are used. Alcohol, polyethylene glycol, triethylene glycol, and triethanolamine are used.
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èŠã§ããã The reaction product constituting the carrier of the present invention is the above (A)
0.5 to 99.5 parts by weight of component, 0.5 to 99.5 parts by weight of component (B), and 1 part per 100 parts by weight of the total amount of component (A) and component (B).
It is a reaction product with ~200 parts by weight of component (C). (A)
The ratio of component (A) to the total amount of component and (B) is 0.5
If the amount is less than % by weight, the resulting reaction product water,
Too soluble in body fluids or blood;
On the other hand, if it exceeds 99.5% by weight, the ability to immobilize physiologically active substances will be significantly reduced, and moldability, film-forming properties, and threadability will deteriorate. It is necessary that the proportion of is 0.5 to 99.5% by weight, preferably 20 to 99.5% by weight, particularly preferably 30 to 95% by weight. If the ratio of component (C) to 100 parts by weight of the total amount of components (A) and (B) is less than 1 part by weight, depending on the type and ratio of components (A) and (B), The solubility of the reaction products produced may become too large;
If the amount exceeds 1 part by weight, the ability to immobilize physiologically active substances will be significantly reduced and moldability will also deteriorate.
The proportion of component (C) is 1 to 200 parts by weight, preferably 1 to 200 parts by weight.
It is necessary to use 150 parts by weight, particularly preferably 20 to 100 parts by weight.
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ããã°ããã The carrier of the present invention includes, for example, component (A), component (B), and (C)
It can be prepared by blending the ingredients in any manner and order, shaping the blend, and then subjecting it to heat treatment. The most preferred method for blending the three components is to dissolve the three components in water or an organic solvent such as acetone or alcohol. Heat treatment is usually performed at a temperature of 20 to 200â for 1 minute to 72
It will be done for about an hour. Molding can be easily carried out by known dry methods, wet methods, etc., and supports in the form of films, threads, nonwoven fabrics, pellets, granules, etc. can be obtained. The carrier of the present invention also includes one whose surface is coated with the above reaction product. In order to prepare such a carrier, for example, a molded article may be coated with a mixture of components (A), (B) and (C), and then heat treated.
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æ¡çšãããã As a method for immobilizing a physiologically active substance on the carrier of the present invention, for example, a method of immersing the carrier in a solution of a physiologically active substance, a method of spraying a solution of a physiologically active substance onto the carrier, etc. can be adopted. When the tube is tube-shaped, a method of circulating a physiologically active substance solution inside the tube is preferably adopted.
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ããšãæå³ããã Immobilization as used in the present invention means insolubilizing a physiologically active substance by chemical bonding and making it remain on a carrier, but more specifically, it refers to both permanent immobilization and sustained release immobilization. means. Permanent immobilization means that the immobilized bioactive substance does not leave the carrier at the point of use, while sustained release immobilization means that it gradually separates from the carrier at the point of use. means.
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åãè¡ãªãã°åŸæŸçåºå®åãè¡ãªããã The carrier of the present invention has the feature that permanent immobilization and sustained release immobilization can be carried out as appropriate depending on the purpose, and this is a great advantage as a carrier. For example, permanent fixation can be achieved by heat treating the carrier at a temperature of about 100 to 140°C for several hours and then fixing it at room temperature or below. Sustained release immobilization can be achieved by immobilization after immersion for a period of time.
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ããã The carrier of the present invention on which a physiologically active substance is immobilized has various uses. For example, it is used as a so-called immunoadsorbent, in which an antigen or antibody is immobilized and the corresponding antigen or antibody is removed. or by immobilizing drugs such as antibiotics or anticancer drugs so that their medicinal effects are exerted when they are used.
Antithrombotic agents can be immobilized and used to prevent blood coagulation when they are used. When used as an immunoadsorbent, it is often filled into a column and used as a filter for filtration. A material having a denier of 10 denier or less and a large surface area per mass is preferably used.
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è¡ã«ããèçã®çºçãæŒããããšãã§ããã There are many possible uses for the immunoadsorbent in which antigens and antibodies as described above are immobilized on the carrier of the present invention, but in particular, the immunoadsorbent in which the HBs antibody is immobilized is
The onset of hepatitis caused by blood transfusion has been known for a long time, and is highly effective in preventing hepatitis, and it is now well known that hepatitis is classified into type A, type B, and nonA-nonB types. Among these, the most notable is hepatitis B, which is caused by infection with the hepatitis B virus. If used, this hepatitis B virus can be efficiently adsorbed. Therefore, if this filter is used to filter blood, the hepatitis B virus in the blood will be removed, and the onset of hepatitis due to blood circulation can be suppressed.
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ããã Hereinafter, the present invention will be explained in more detail with reference to Examples. Note that "parts" in the examples mean "parts by weight."
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Gantrez AN169ïŒGAF瀟補ãã¡ãã«ããã«ãš
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ãåŸãäžå€ã§ãã€ããExamples 1 to 3 1 part of Gantrez AN169 (manufactured by GAF, copolymer of methyl vinyl ether and maleic anhydride),
1 part of SMA3000 (manufactured by ARCO Chemical, copolymer of styrene and maleic anhydride) and magrogol
400 (manufactured by Matsumoto Yushi Co., Ltd., polyethylene glycol) 1
1 part was dissolved in 7 parts of acetone, and a 10 denier thread was produced from this solution by dry spinning. The obtained yarn was heat treated at 140°C for 2 hours. This product was insoluble in hot water. Take 1 g of each of these threads and prepare three types of samples. Sample A is added to an aqueous solution of Hebusbrin (manufactured by Midori Juji Co., Ltd., dried anti-hepatitis B human immunoglobulin) [200 mg/50 ml], and sample B is added to an aqueous solution of dibekacin sulfate (PH). (adjusted to 8) [100
When sample C was immersed in urokinase aqueous solution [100 mg/50 ml] at 7°C for 24 hours, it was found that sample A contained 60 hebsbrin.
45 mg of dibekacin sulfate was immobilized on sample B, and 40 ft of urokinase was immobilized on sample C. The activity of the immobilized material remained unchanged after storage in air at 7° C. for 3 months.
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ããComparative Example 1 0.3 parts of Gantrez AN169 and 99.7 parts of SMA3000
and 50 parts of Magrogol 400 were dissolved in 350 parts of acetone, and spinning was attempted in the same manner as in Example 1 using this solution, but spinnability was poor and spinning was impossible.
æ¯èŒäŸ ïŒ
99.7éšã®Gantrez AN169ãšã0.3éšã®SMA3000
ãšã50éšã®ãã°ããŽãŒã«400ãšã350éšã®ã¢ã»ãã³
ã«æº¶è§£ãå®æœäŸïŒãšåæ§ã®çŽ¡ç³žãè¡ãã11ãããŒ
ã«ã®ç³žãåŸãããã®ç³žã«140âã«ãŠïŒæéç±åŠç
ãæœãããããã®ãã®ã¯å·æ°Žäžæº¶ã§ãã€ããç±æ°Ž
ã«ã¯æº¶è§£ãããComparative Example 2 99.7 parts of Gantrez AN169 and 0.3 parts of SMA3000
and 50 parts of Magrogol 400 were dissolved in 350 parts of acetone and spun in the same manner as in Example 1 to obtain a thread of 11 denier. This yarn was heat treated at 140°C for 2 hours. This product was insoluble in cold water but soluble in hot water.
å®æœäŸ ïŒ
ïŒéšã®Gantrez AN169ãšãïŒéšã®SMA3000ãš
ïŒéšã®ãã°ããŽãŒã«400ã17éšã®ã¢ã»ãã³ã«æº¶è§£
ãããã®æº¶æ¶²ãã也åŒçŽ¡ç³žæ³ã«ããïŒãããŒã«ã®
糞ãäœæãããåŸããã糞ã«120âã«ãŠïŒæéã®
ç±åŠçãæœãããããã®ãã®ã¯ç±æ°Žã«äžæº¶ã§ãã€
ãããã®ç³žïŒïœãããã¹ããªã³æ°Žæº¶æ¶²ã200mgïŒ
50mlãã«ïŒâã«ãŠ24æé浞挬ãããšãã90mgã®ã
ãã¹ããªã³ãåºå®åããããExample 4 1 part of Gantrez AN169, 1 part of SMA3000, and 1 part of Magrogol 400 were dissolved in 17 parts of acetone, and a 3-denier thread was produced from this solution by dry spinning. The obtained yarn was heat treated at 120°C for 3 hours. This product was insoluble in hot water. 1g of this thread was mixed with Hebusbrin aqueous solution [200mg/
50ml] at 7°C for 24 hours, 90mg of hebusbrin was immobilized.
ãã®ç³žã容é10mlã®ã«ã©ã ã«å
ãŠããããã®ã«
ã©ã ãéããŠHBsæåéïŒïŒ215ã®è¡æŒ¿ããéã
ããšãããéããŠããè¡æŒ¿ã®æåéã¯ïŒïŒ22ã«æž
å°ããŠããããã®çµæããã¿ãŠå€éã®HBsæåã
HBsæäœã®åºå®åãããæ¬å®æœäŸã®ç³žã«åžçãã
ãããšãæããã§ããã When this thread was filled in a column with a capacity of 10 ml and plasma with an amount of HBs antigen of 1: 2.15 was filtered through this column, the amount of antigen in the filtered plasma was reduced to 1: 2.2 . A large amount of HB s antigen
It is clear that the HBs antibody was adsorbed to the immobilized thread of this example.
å®æœäŸ ïŒ
ç¡æ°Žãã¬ã€ã³é
žãšãšãã«ããã«ãšãŒãã«ã®å
±é
åäœïŒå
±éåæ¯ïŒïŒïŒãååé50äžïŒïŒéšãšãç¡
æ°Žãã¬ã€ã³é
žãšãšãã¬ã³ã®å
±éåäœïŒå
±éåæ¯
ïŒïŒïŒãååé50äžïŒ1.5éšãšãããªãšãã¬ã³ã°
ãªã³ãŒã«0.5éšãïŒéšã®ã¢ã»ãã³ã«æº¶è§£ããå®æœ
äŸïŒãšåæ§ã«ããŠ10ãããŒã«ã®ç³žãåŸããåŸãã
ã糞ã120âã«ãŠïŒæéç±åŠçãè¡ã€ãåŸãå®æœ
äŸïŒãšåæ§ã®åºå®åæäœãè¡ã€ããšããããã¹ã
ãªã³ã55mgãç¡«é
žãžãã«ã·ã³ã50mgããŠããããŒ
ãŒã60mgåºå®åããããåºå®åãããç©è³ªã®æŽ»æ§
ã¯ïŒã±æçµéåŸãäžå€ã§ãã€ããExample 5 1 part of a copolymer of maleic anhydride and ethyl vinyl ether (copolymerization ratio 1:1, molecular weight 500,000) and a copolymer of maleic anhydride and ethylene (copolymerization ratio 1:1, molecular weight 500,000) 1.5 parts of triethylene glycol and 0.5 parts of triethylene glycol were dissolved in 7 parts of acetone, and a 10 denier thread was obtained in the same manner as in Example 1. The obtained thread was heat-treated at 120° C. for 3 hours, and then immobilized in the same manner as in Example 1, resulting in immobilization of 55 mg of hebusbulin, 50 mg of dibekacin sulfate, and 60 mg of urokinase. The activity of the immobilized substance remained unchanged even after 3 months.
å®æœäŸ ïŒ
10éšã®Gantrez AN139ãšã90éšã®ã€ãœãã³â
110ïŒã¯ã©ã¬è£œãç¡æ°Žãã¬ã€ã³é
žãšã€ãœããã¬ã³ãš
ã®å
±éåäœïŒãšã30éšã®ããªããã«ã¢ã«ã³ãŒã«
ïŒéå床1700ãå®å
šããåç©ïŒãšã2600éšã®æ°Žã«
溶解ãããã®æ°Žæº¶æ¶²ãããªãšã¹ãã«ãã€ã«ã äžã«
æµå»¶ãã140âã«ãŠïŒæéç±åŠçãè¡ããåã
30ÎŒã®ãã€ã«ã ãäœæãããåŸããããã€ã«ã ã
ïŒcmåæ¹ã«è£æããå®æœäŸïŒãšåæ§ã®åºå®åæäœ
ãè¡ã€ããšãããããã¹ããªã³ã40mgãç¡«é
žãžã
ã«ã·ã³ã35mgããŠããããŒãŒã30mgåºå®åãã
ããåºå®åããããã€ã«ã ã25âã®æ°Žã«10æ¥é浞
挬ããåŸæŽ»æ§ã¯åºå®ååœåãšå€åããªãã€ããExample 6 10 parts Gantrez AN139 and 90 parts Isoban
110 (manufactured by Kuraray, a copolymer of maleic anhydride and isobutylene) and 30 parts of polyvinyl alcohol (degree of polymerization 1700, completely saponified product) were dissolved in 2600 parts of water, and this aqueous solution was poured onto a polyester film. Rolled out, heat treated at 140â for 5 hours,
A 30Ό film was made. The obtained film was cut into 5 cm squares and immobilized in the same manner as in Example 1, resulting in immobilization of 40 mg of hebusbulin, 35 mg of dibekacin sulfate, and 30 mg of urokinase. After the immobilized film was immersed in water at 25°C for 10 days, the activity remained unchanged from that at the beginning of immobilization.
å®æœäŸ ïŒ
ïŒéšã®Gantrez AN169ãšãïŒéšã®SMA3000
ãšã1.5éšã®ãã°ããŽãŒã«400ãšãã100éšã®ã¢ã»
ãã³ã«æº¶è§£ãã溶液ãäœæãããã®ãã®ã«ã·ãªã³
ãŒã³è£œã«ããŒãã«ã宀枩ã«ãŠïŒåé浞挬ããåŸã
åãåºã120âã§ïŒæéç±åŠçãè¡ã€ããšããã
ã«ããŒãã«è¡šé¢ã«åã10ÎŒã®è¢«èŠå±€ã圢æãã
ãããã®è¢«èŠå±€ã¯ç±æ°Žäžæº¶ã§ãã€ããã²ãã€ã¥ã
ãŠãã®ã«ããŒãã«ãããªããã·ïŒ¢æ°Žæº¶æ¶²ã800000
åäœïŒ100mlãã«ïŒâã§12æé浞挬ãããšãã
400000åäœã®ããªããã·ã³ïŒ¢ãåºå®åããããåº
å®åã«ããŒãã«ã37âã®æ°Žäžã«40æ¥é浞挬ããåŸ
ãããªããã·ã³ïŒ¢ã®è¬çå¹æã¯å
åã«èªããã
ããExample 7 Two parts of Gantrez AN169 and two parts of SMA3000
A solution was prepared by dissolving 1.5 parts of Magrogol 400 in 100 parts of acetone, and a silicone catheter was immersed in this solution for 3 minutes at room temperature.
When taken out and heat treated at 120â for 2 hours,
A coating layer with a thickness of 10 ÎŒm was formed on the surface of the catheter. This coating layer was insoluble in hot water. Subsequently, this catheter was treated with Polymixi B aqueous solution [800000
unit/100ml] for 12 hours at 7â
400,000 units of polymyxin B were immobilized. Even after the immobilized catheter was immersed in water at 37°C for 40 days, the pharmacological effects of polymyxin B were fully observed.
å®æœäŸ ïŒ
ïŒéšã®Gantrez AN169ãšãïŒéšã®SMA3000
ãšãïŒéšã®ãã°ããŽãŒã«400ãšã20éšã®ã¢ã»ãã³
ã«æº¶è§£ãããã®æ°Žæº¶æ¶²ãããªãšã¹ãã«ãã€ã«ã äž
ã«æµå»¶ãã140âã«ãŠïŒæéç±åŠçãè¡ããåã
20ÎŒã®ãã€ã«ã ãäœæããããã®ãã€ã«ã ã¯ç±æ°Ž
äžæº¶ã§ãã€ãããã®ãã€ã«ã ïŒïœãγâã°ãããª
ã³ïŒã·ã°ãã±ãã«ã«ç€Ÿè£œHUMAN COHN
FRACTIONïŒæ°Žæº¶æ¶²ã200mgïŒ150mlãã«ïŒâ
ã«ãŠïŒæé浞挬ãããšãã60mgã®Î³âã°ãããªã³
ãåºå®åããããExample 8 Two parts of Gantrez AN169 and two parts of SMA3000
and 2 parts of Magrogol 400 were dissolved in 20 parts of acetone, this aqueous solution was cast onto a polyester film, and heat treated at 140°C for 3 hours to determine the thickness.
A 20Ό film was made. This film was insoluble in hot water. 1 g of this film was mixed with γ-globulin (HUMAN COHN manufactured by Sigma Chemical Co., Ltd.).
FRACTION) aqueous solution [200mg/150ml] at 7â
60 mg of γ-globulin was immobilized.
æ¯èŒäŸ ïŒ
ïŒéšã®Gantrez AN169ãšïŒéšã®ãã°ããŽãŒã«
400ã20éšã®ã¢ã»ãã³ã«æº¶è§£ããå®æœäŸïŒãšåæ§
ã«ããŠåã25ÎŒã®ãã€ã«ã ãäœæããããã®ãã€
ã«ã ïŒïœãå®æœäŸïŒãšåæ§ã«Î³âã°ãããªã³æ°Žæº¶
液ã«æµžæŒ¬ããããã€ã«ã ã¯è¥å¹²æº¶è§£ãããããã€
ã«ã ïŒïœãããã«æç®ããγâã°ãããªã³ã®åºå®
åéã¯58mgã§ãã€ããComparative example 3 4 parts of Gantrez AN169 and 2 parts of tuna gor
400 was dissolved in 20 parts of acetone, and a 25 Όm thick film was prepared in the same manner as in Example 8. 1 g of this film was immersed in a γ-globulin aqueous solution in the same manner as in Example 8. Although the film was slightly dissolved, the amount of γ-globulin immobilized per gram of film was 58 mg.
æ¯èŒäŸ ïŒ
ïŒéšã®SMA3000ãšïŒéšã®ãã°ããŽãŒã«400ã20
éšã®ã¢ã»ãã³ã«æº¶è§£ããå®æœäŸïŒãšåæ§ã«ããŠå
ã10ÎŒã®ãã€ã«ã ãäœæããããã®ãã€ã«ã ã¯ç±
æ°Žäžæº¶ã§ãã€ãããã®ãã€ã«ã ïŒïœãå®æœäŸïŒãš
åæ§ã«Î³âã°ãããªã³æ°Žæº¶æ¶²ã«æµžæŒ¬ãããšããã
ãã€ã«ã ã«åºå®åãããγâã°ãããªã³ã¯ïŒmgã«
ãããªãã€ããComparative example 4 4 parts of SMA3000 and 2 parts of Tuna Gol 400 for 20
A film having a thickness of 10 Όm was prepared in the same manner as in Example 8. This film was insoluble in hot water. When 1 g of this film was immersed in a γ-globulin aqueous solution in the same manner as in Example 8,
Only 4 mg of γ-globulin was immobilized on the film.
Claims (1)
ãœããã¬ã³åã³ãããã¬ã³ãããªã矀ããéžã°ã
ãå°ãªããšãäžã€ã®ã¢ãããŒãšã®å ±éåäœ0.5ã
99.5éééšãšã(B)ç¡æ°Žãã¬ã€ã³é žãšã¡ãã«ããã«
ãšãŒãã«ããšãã«ããã«ãšãŒãã«ããã¿ã³ãžãªãŒ
ã«ããã«ãšãŒãã«åã³é ¢é žããã«ãããªã矀ãã
éžã°ããå°ãªããšãäžã€ã®ã¢ãããŒãšã®å ±éåäœ
0.5ã99.5éééšãšã(A)ãš(B)ã®åèšé100éééšã«
察ãïŒã200éééšã®(C)ç¡æ°Žãã¬ã€ã³é žåºãŸãã¯
ç¡æ°Žãã¬ã€ã³é žåºãå æ°Žå解ãåããŠçããã«ã«
ããã·ã«åºãšã®åå¿æ§ããã€å®èœåºãïŒååäžã«
ïŒå以äžå«æããååç©ã«(A)ãš(B)ãåå¿ããåå¿
çæç©ãããªãçç掻æ§ç©è³ªåºå®åçšæ äœã1 (A) Copolymer of maleic anhydride and at least one monomer selected from the group consisting of styrene, ethylene, isobutylene and propylene 0.5~
99.5 parts by weight and (B) a copolymer of maleic anhydride and at least one monomer selected from the group consisting of methyl vinyl ether, ethyl vinyl ether, butanediol vinyl ether, and vinyl acetate.
0.5 to 99.5 parts by weight, and 1 to 200 parts by weight of (C) a maleic anhydride group or a carboxyl group generated by hydrolysis of a maleic anhydride group based on 100 parts by weight of the total amount of (A) and (B). A carrier for immobilizing a physiologically active substance, which is made of a reaction product obtained by reacting (A) and (B) with a compound containing two or more functional groups in one molecule with the reactivity of .
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP56182728A JPS5883633A (en) | 1981-11-13 | 1981-11-13 | Carrier for immobilization of physiologically active substance |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP56182728A JPS5883633A (en) | 1981-11-13 | 1981-11-13 | Carrier for immobilization of physiologically active substance |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS5883633A JPS5883633A (en) | 1983-05-19 |
JPH0257580B2 true JPH0257580B2 (en) | 1990-12-05 |
Family
ID=16123399
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP56182728A Granted JPS5883633A (en) | 1981-11-13 | 1981-11-13 | Carrier for immobilization of physiologically active substance |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS5883633A (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE60315133T2 (en) * | 2002-02-15 | 2008-04-10 | PPG Industries Ohio, Inc., Cleveland | AQUEOUS, FILM-FORMING COMPOSITIONS CONTAINING ALTERNATIVE COPOLYMERS OF ISOBUTYLENE |
EP1474478B1 (en) * | 2002-02-15 | 2008-12-31 | PPG Industries Ohio, Inc. | Waterborne thermosetting compositions containing alternating copolymers of isobutylene type monomers |
US7696138B2 (en) * | 2006-07-28 | 2010-04-13 | Afton Chemical Corporation | Alkyl acrylate copolymer dispersants and uses thereof |
JP2008260887A (en) * | 2007-04-13 | 2008-10-30 | Yokohama Rubber Co Ltd:The | Thermoplastic elastomer and thermoplastic elastomer composition |
CN101864408A (en) * | 2010-05-25 | 2010-10-20 | äžåœç§åŠé¢è¿çšå·¥çšç 究æ | Preparation method of nanometer fiber immobilization beta-D-galactosidase |
-
1981
- 1981-11-13 JP JP56182728A patent/JPS5883633A/en active Granted
Also Published As
Publication number | Publication date |
---|---|
JPS5883633A (en) | 1983-05-19 |
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