JPH01217035A - Production of crosslinked polymer particle - Google Patents
Production of crosslinked polymer particleInfo
- Publication number
- JPH01217035A JPH01217035A JP63044832A JP4483288A JPH01217035A JP H01217035 A JPH01217035 A JP H01217035A JP 63044832 A JP63044832 A JP 63044832A JP 4483288 A JP4483288 A JP 4483288A JP H01217035 A JPH01217035 A JP H01217035A
- Authority
- JP
- Japan
- Prior art keywords
- particles
- oxirane ring
- ether
- compound
- water
- 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.)
- Pending
Links
- 239000002245 particle Substances 0.000 title claims abstract description 65
- 229920006037 cross link polymer Polymers 0.000 title claims description 13
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 125000000466 oxiranyl group Chemical group 0.000 claims abstract description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 150000001875 compounds Chemical class 0.000 claims abstract description 20
- -1 glycidyl monovinyl compound Chemical class 0.000 claims abstract description 15
- 150000005846 sugar alcohols Polymers 0.000 claims abstract description 13
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 238000010557 suspension polymerization reaction Methods 0.000 claims abstract description 11
- 150000001350 alkyl halides Chemical class 0.000 claims abstract description 8
- 229920001289 polyvinyl ether Polymers 0.000 claims abstract description 7
- 229920001290 polyvinyl ester Polymers 0.000 claims abstract description 6
- JJRUAPNVLBABCN-UHFFFAOYSA-N 2-(ethenoxymethyl)oxirane Chemical compound C=COCC1CO1 JJRUAPNVLBABCN-UHFFFAOYSA-N 0.000 claims description 11
- 239000007900 aqueous suspension Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 4
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 claims description 3
- 230000000379 polymerizing effect Effects 0.000 claims description 2
- 239000004593 Epoxy Substances 0.000 claims 1
- 150000002924 oxiranes Chemical class 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 18
- 238000010559 graft polymerization reaction Methods 0.000 abstract description 9
- 238000012856 packing Methods 0.000 abstract description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract description 6
- 239000012736 aqueous medium Substances 0.000 abstract description 6
- 229920000642 polymer Polymers 0.000 abstract description 6
- CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 abstract description 3
- 230000003301 hydrolyzing effect Effects 0.000 abstract description 3
- 229920002554 vinyl polymer Polymers 0.000 abstract description 3
- 239000003505 polymerization initiator Substances 0.000 abstract description 2
- 239000007788 liquid Substances 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000000499 gel Substances 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
- 238000004811 liquid chromatography Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 7
- 239000000178 monomer Substances 0.000 description 7
- 238000006116 polymerization reaction Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 6
- GYZLOYUZLJXAJU-UHFFFAOYSA-N diglycidyl ether Chemical compound C1OC1COCC1CO1 GYZLOYUZLJXAJU-UHFFFAOYSA-N 0.000 description 6
- 239000000945 filler Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 238000011088 calibration curve Methods 0.000 description 5
- 229920001577 copolymer Polymers 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 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
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 108010038061 Chymotrypsinogen Proteins 0.000 description 4
- 241000238557 Decapoda Species 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 102000009843 Thyroglobulin Human genes 0.000 description 4
- 108010034949 Thyroglobulin Proteins 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Substances CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 229940125396 insulin Drugs 0.000 description 4
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 235000021317 phosphate Nutrition 0.000 description 4
- 229960002175 thyroglobulin Drugs 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- ATVJXMYDOSMEPO-UHFFFAOYSA-N 3-prop-2-enoxyprop-1-ene Chemical compound C=CCOCC=C ATVJXMYDOSMEPO-UHFFFAOYSA-N 0.000 description 3
- DBCAQXHNJOFNGC-UHFFFAOYSA-N 4-bromo-1,1,1-trifluorobutane Chemical compound FC(F)(F)CCCBr DBCAQXHNJOFNGC-UHFFFAOYSA-N 0.000 description 3
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 3
- 108010052832 Cytochromes Proteins 0.000 description 3
- 102000018832 Cytochromes Human genes 0.000 description 3
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108010058846 Ovalbumin Proteins 0.000 description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 229940000635 beta-alanine Drugs 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000000084 colloidal system Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 108010074605 gamma-Globulins Proteins 0.000 description 3
- 238000009775 high-speed stirring Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 229940092253 ovalbumin Drugs 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 3
- 229920001451 polypropylene glycol Polymers 0.000 description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- KVNYFPKFSJIPBJ-UHFFFAOYSA-N 1,2-diethylbenzene Chemical compound CCC1=CC=CC=C1CC KVNYFPKFSJIPBJ-UHFFFAOYSA-N 0.000 description 2
- KUDUQBURMYMBIJ-UHFFFAOYSA-N 2-prop-2-enoyloxyethyl prop-2-enoate Chemical compound C=CC(=O)OCCOC(=O)C=C KUDUQBURMYMBIJ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 description 2
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229920013820 alkyl cellulose Polymers 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 229940059574 pentaerithrityl Drugs 0.000 description 2
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 229920001515 polyalkylene glycol Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000012798 spherical particle Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- BOOBDAVNHSOIDB-UHFFFAOYSA-N (2,3-dichlorobenzoyl) 2,3-dichlorobenzenecarboperoxoate Chemical compound ClC1=CC=CC(C(=O)OOC(=O)C=2C(=C(Cl)C=CC=2)Cl)=C1Cl BOOBDAVNHSOIDB-UHFFFAOYSA-N 0.000 description 1
- KOMNUTZXSVSERR-UHFFFAOYSA-N 1,3,5-tris(prop-2-enyl)-1,3,5-triazinane-2,4,6-trione Chemical compound C=CCN1C(=O)N(CC=C)C(=O)N(CC=C)C1=O KOMNUTZXSVSERR-UHFFFAOYSA-N 0.000 description 1
- UBRWPVTUQDJKCC-UHFFFAOYSA-N 1,3-bis(2-tert-butylperoxypropan-2-yl)benzene Chemical compound CC(C)(C)OOC(C)(C)C1=CC=CC(C(C)(C)OOC(C)(C)C)=C1 UBRWPVTUQDJKCC-UHFFFAOYSA-N 0.000 description 1
- UWFRVQVNYNPBEF-UHFFFAOYSA-N 1-(2,4-dimethylphenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(C)C=C1C UWFRVQVNYNPBEF-UHFFFAOYSA-N 0.000 description 1
- GDXHBFHOEYVPED-UHFFFAOYSA-N 1-(2-butoxyethoxy)butane Chemical compound CCCCOCCOCCCC GDXHBFHOEYVPED-UHFFFAOYSA-N 0.000 description 1
- STMDPCBYJCIZOD-UHFFFAOYSA-N 2-(2,4-dinitroanilino)-4-methylpentanoic acid Chemical compound CC(C)CC(C(O)=O)NC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O STMDPCBYJCIZOD-UHFFFAOYSA-N 0.000 description 1
- JJBFVQSGPLGDNX-UHFFFAOYSA-N 2-(2-methylprop-2-enoyloxy)propyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC(C)COC(=O)C(C)=C JJBFVQSGPLGDNX-UHFFFAOYSA-N 0.000 description 1
- XMNIXWIUMCBBBL-UHFFFAOYSA-N 2-(2-phenylpropan-2-ylperoxy)propan-2-ylbenzene Chemical compound C=1C=CC=CC=1C(C)(C)OOC(C)(C)C1=CC=CC=C1 XMNIXWIUMCBBBL-UHFFFAOYSA-N 0.000 description 1
- WFUGQJXVXHBTEM-UHFFFAOYSA-N 2-hydroperoxy-2-(2-hydroperoxybutan-2-ylperoxy)butane Chemical compound CCC(C)(OO)OOC(C)(CC)OO WFUGQJXVXHBTEM-UHFFFAOYSA-N 0.000 description 1
- VFZKVQVQOMDJEG-UHFFFAOYSA-N 2-prop-2-enoyloxypropyl prop-2-enoate Chemical compound C=CC(=O)OC(C)COC(=O)C=C VFZKVQVQOMDJEG-UHFFFAOYSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- CARNFEUGBMWTON-UHFFFAOYSA-N 3-(2-prop-2-enoxyethoxy)prop-1-ene Chemical compound C=CCOCCOCC=C CARNFEUGBMWTON-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical group C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 1
- 101100228210 Caenorhabditis elegans gly-7 gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- YIVJZNGAASQVEM-UHFFFAOYSA-N Lauroyl peroxide Chemical compound CCCCCCCCCCCC(=O)OOC(=O)CCCCCCCCCCC YIVJZNGAASQVEM-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000005396 acrylic acid ester group Chemical group 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- YGBGWFLNLDFCQL-UHFFFAOYSA-N boron zinc Chemical compound [B].[Zn] YGBGWFLNLDFCQL-UHFFFAOYSA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- XENVCRGQTABGKY-ZHACJKMWSA-N chlorohydrin Chemical compound CC#CC#CC#CC#C\C=C\C(Cl)CO XENVCRGQTABGKY-ZHACJKMWSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 239000007771 core particle Substances 0.000 description 1
- 108010039354 cytochrome C7 Proteins 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- 125000004386 diacrylate group Chemical group 0.000 description 1
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical compound OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 1
- 125000003700 epoxy group Chemical group 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 239000007863 gel particle Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 125000003055 glycidyl group Chemical group C(C1CO1)* 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229920013821 hydroxy alkyl cellulose Polymers 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- ZQMHJBXHRFJKOT-UHFFFAOYSA-N methyl 2-[(1-methoxy-2-methyl-1-oxopropan-2-yl)diazenyl]-2-methylpropanoate Chemical compound COC(=O)C(C)(C)N=NC(C)(C)C(=O)OC ZQMHJBXHRFJKOT-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- RPQRDASANLAFCM-UHFFFAOYSA-N oxiran-2-ylmethyl prop-2-enoate Chemical compound C=CC(=O)OCC1CO1 RPQRDASANLAFCM-UHFFFAOYSA-N 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920005650 polypropylene glycol diacrylate Polymers 0.000 description 1
- 229920005651 polypropylene glycol dimethacrylate Polymers 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- QPILZZVXGUNELN-UHFFFAOYSA-M sodium;4-amino-5-hydroxynaphthalene-2,7-disulfonate;hydron Chemical compound [Na+].OS(=O)(=O)C1=CC(O)=C2C(N)=CC(S([O-])(=O)=O)=CC2=C1 QPILZZVXGUNELN-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- GJBRNHKUVLOCEB-UHFFFAOYSA-N tert-butyl benzenecarboperoxoate Chemical compound CC(C)(C)OOC(=O)C1=CC=CC=C1 GJBRNHKUVLOCEB-UHFFFAOYSA-N 0.000 description 1
- SWAXTRYEYUTSAP-UHFFFAOYSA-N tert-butyl ethaneperoxoate Chemical compound CC(=O)OOC(C)(C)C SWAXTRYEYUTSAP-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 108010094139 tumor-globulin Proteins 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
Landscapes
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Polyethers (AREA)
Abstract
Description
【発明の詳細な説明】 (産業上の利用分野) 本発明は、液体クロマトグラフィー用充填剤。[Detailed description of the invention] (Industrial application field) The present invention is a packing material for liquid chromatography.
特に水系用液体クロマトグラフィー用充填剤或いはそれ
らの合成用中間体として有用な多孔性の架橋重合体粒子
の製造法に関する。In particular, the present invention relates to a method for producing porous crosslinked polymer particles useful as fillers for aqueous liquid chromatography or intermediates for their synthesis.
(従来の技術)
従来、液体クロマトグラフィー用充填剤としては、(1
)スチレンと架橋性単緻体の共重合体ゲル〔ジエー・シ
ー・ムーア、ジャーナル・オプeポリマー・サイエンス
(J、 C,Moore+ J、 Polym。(Prior art) Conventionally, as a packing material for liquid chromatography, (1
) Copolymer gel of styrene and crosslinkable single compact [CG Moore, Journal Ope Polymer Science (J, C, Moore+ J, Polym.
Sci、)、A2,835(1964)]、■アクリル
酸エステル系単量体と架橋性単量体ポリアルキレングリ
コールのポリアクリル酸エステルの共重合体ゲル(特開
昭55−99068号公報)、■ポリビニルアルコール
をエピクロルヒドリンで架橋したゲル(特開昭52−1
38077号公報)。Sci, ), A2, 835 (1964)], ■ Copolymer gel of polyacrylic ester of acrylic ester monomer and crosslinkable monomer polyalkylene glycol (Japanese Unexamined Patent Publication No. 55-99068), ■Gel made by crosslinking polyvinyl alcohol with epichlorohydrin (Unexamined Japanese Patent Publication No. 52-1
Publication No. 38077).
■酢酸ビニルとトリアリルイソシアヌレートの共重合体
ゲルを加水分解したポリビニルアルコールゲル(特開昭
57−30945号公報)、■アクリル酸エステル系単
量体又はアクリルアミドと架橋性単量体メチレンビスア
クリルアミドの共重合体ゲル(鈴木輝−他1日本化学会
誌、1975゜1756)、■デキストランをエピクロ
ルヒドリンで架橋したゲル(特公昭47−21405号
公報)、■シリカゲルやガラス等の無機系ゲルを化学修
飾したもの〔ニス・エイチ・チャン、アール・ノニル、
エフ・イー・レグニール、アナリテイカル・ケミストリ
ー(S、 a Chang * R,Noel mF’
、E、Regniers Anal、 Chem、
)48.1839(1976))等が知られている。■Polyvinyl alcohol gel obtained by hydrolyzing a copolymer gel of vinyl acetate and triallyl isocyanurate (Japanese Patent Application Laid-Open No. 57-30945), ■Acrylic acid ester monomer or acrylamide and crosslinkable monomer methylenebisacrylamide copolymer gel (Suzuki Teru et al. 1 Journal of the Chemical Society of Japan, 1975゜1756), ■Gel made by crosslinking dextran with epichlorohydrin (Japanese Patent Publication No. 1983-21405), ■Chemical modification of inorganic gels such as silica gel and glass. What I did [Nis H Chan, Earl Nonil,
F.E. Regnir, Analytical Chemistry (S, a Chang * R, Noel mF'
,E,Regniers Anal,Chem,
) 48.1839 (1976)) are known.
(発明が解決しようとする線題)
上記■のゲルは、有機溶媒を溶離液とする液体クロマト
グラフィーでは優れた充填剤となり得るが、水とのなじ
みが良くないため、水系では使用できない。上記の■、
■及び■のゲルは、若干疎水性が残っているため、被分
離物質に疎水性があると、疎水性吸着を起こし1分子ふ
るい分離を行う場合には都合が悪い。(Problem to be Solved by the Invention) The above gel can be an excellent packing material in liquid chromatography using an organic solvent as an eluent, but it cannot be used in an aqueous system because it is not compatible with water. ■ above,
The gels (2) and (2) remain slightly hydrophobic, so if the substance to be separated is hydrophobic, hydrophobic adsorption will occur, which is inconvenient when performing single molecule sieving separation.
上記の■及び■のゲルは、疎水性ではないが。The gels of ■ and ■ above are not hydrophobic.
機械的強度に乏しく、高圧がかかる高速液体クロマトグ
ラフィー用カラム充填剤として用(へることはできない
。また、■のゲルは疎水性でなく9機械的強度もあるが
、アルカリに弱く、耐久性に劣るという欠点があった。It has poor mechanical strength and is used as a column filler for high-performance liquid chromatography where high pressure is applied (it cannot be damaged.Also, the gel in (■) is not hydrophobic and has 9 mechanical strength, but is weak against alkalis and has poor durability. It had the disadvantage of being inferior to
従って1本発明は、このような従来技術の欠点を解決し
、親水性、耐圧性及び耐アルカリ性を有し、液体クロマ
トグラフィー用充填剤或いは液体クロマトグラフィー用
充填剤合成用の中間体として有用な多孔性架橋重合体粒
子を提供することを目的とする。Therefore, the present invention solves the drawbacks of the prior art and provides a material that has hydrophilicity, pressure resistance, and alkali resistance and is useful as a packing material for liquid chromatography or an intermediate for synthesizing a packing material for liquid chromatography. The object is to provide porous crosslinked polymer particles.
(1憬須を解決するための手段)
本発明は、グリシジルモノビニルエステル又はグリシジ
ルモノビニルエーテルCI)ト多価アルコールのポリビ
ニルエステル又は多価アルコールのポリビニルエーテル
(II)を、水と相溶性でない有機溶媒(1)の存在下
で水性懸濁重合させ、更K。(Means for Solving Problem 1) The present invention provides glycidyl monovinyl ester or glycidyl monovinyl ether (CI), a polyvinyl ester of a polyhydric alcohol, or a polyvinyl ether of a polyhydric alcohol (II) in an organic solvent that is not miscible with water. Aqueous suspension polymerization in the presence of (1) and further K.
得られた粒子(A)の(I)成分によるオキシラン環を
加水分解させ、更に、得られた粒子(B )Kオキシラ
ン環を有するアルキルハライドを反応させてオキシラン
環を導入し、このオキシラン環を有する粒子(C)のオ
キシラン環に、オキシラン環を有する化合物をグラフト
重合させることを特徴とする架橋重合体粒子の製造法に
関する。The oxirane ring of the obtained particle (A) due to component (I) is hydrolyzed, and further, the obtained particle (B) is reacted with an alkyl halide having a K oxirane ring to introduce an oxirane ring. The present invention relates to a method for producing crosslinked polymer particles, which comprises graft-polymerizing a compound having an oxirane ring onto the oxirane ring of the particle (C).
次に9本発明の架橋重合体粒子の製造法に用いる各成分
について詳述する。Next, each component used in the method for producing crosslinked polymer particles of the present invention will be described in detail.
本発明に用いるグリシジルモノビニルエステル又はグリ
シジルモノビニルエステルトシては、グリシジルメタク
リレート、グリシジルアクリレート、アリルグリシジル
エーテル等が挙げられるが。Examples of the glycidyl monovinyl ester or glycidyl monovinyl ester used in the present invention include glycidyl methacrylate, glycidyl acrylate, and allyl glycidyl ether.
反応性及び耐アルカリ性を考慮すると、グリシジルメタ
クリレートが好ましい。Considering reactivity and alkali resistance, glycidyl methacrylate is preferred.
また1本発明に用いる多価アルコールのポリビニルエス
テル又ハ多価アルコールのポリビニルエーテルとしては
1例えば、エチレングリコールジメタクリレート、エチ
レングリコールジアクリレート、プロピレングリコール
ジメタクリレート。Examples of polyvinyl esters of polyhydric alcohols and polyvinyl ethers of polyhydric alcohols used in the present invention include ethylene glycol dimethacrylate, ethylene glycol diacrylate, and propylene glycol dimethacrylate.
プロピレングリコールジアクリレートのようなアルキレ
ングリコールジビニルエステル、ポリエチレングリコー
ルジメタクリレート、ポリプロピレングリコールジメタ
クリレート、ポリエチレングリコールジアクリレート、
ポリプロピレングリコールジアクリレート等のポリアル
キレングリコールのジビニルエステル、グリセリンのジ
又はトリアクリレート、グリセリンのジ又はトリメタク
リレート、トリメチロールプロパンジ又はトリメタクリ
レート、トリメチロールプロパンジ又はトリアクリレー
ト、テトラメチロールメタンジ、トリ又はテトラメタク
リレート、テトラメチロールメタンジ、トリ又はテトラ
アクリレート、エチレングリコールジアリルエーテル、
フロピレンゲリコールジアリルエーテル、ポリエチレン
グリコールジアリルエーテル、ポリプロピレングリコー
ルジアリルエーテル、グリセリンジ又はトリアリルエー
テル、トリメチロールプロ・くンジ又はトリアリルエー
テル、テトラメチロールメタンジ、トリ又はテトラアリ
ルエーテル等が挙げられるが1反応性並びに生成した多
孔性の架橋重合体粒子の親水性及び耐圧性を考慮すると
、エチレングリコールジメタクリレート、テトラメチロ
ールメタ/ジ。Alkylene glycol divinyl esters such as propylene glycol diacrylate, polyethylene glycol dimethacrylate, polypropylene glycol dimethacrylate, polyethylene glycol diacrylate,
Divinyl esters of polyalkylene glycols such as polypropylene glycol diacrylate, di- or triacrylates of glycerin, di- or trimethacrylates of glycerin, trimethylolpropane di- or trimethacrylates, trimethylolpropane di- or triacrylates, tetramethylolmethane di-, tri- or Tetramethacrylate, tetramethylolmethanedi, tri- or tetraacrylate, ethylene glycol diallyl ether,
Examples include fluoropylene gelyl diallyl ether, polyethylene glycol diallyl ether, polypropylene glycol diallyl ether, glycerin di- or triallyl ether, trimethylol pro-kundi or triallyl ether, tetramethylolmethane di, tri- or tetraallyl ether, etc. 1 reactivity and the hydrophilicity and pressure resistance of the produced porous crosslinked polymer particles, ethylene glycol dimethacrylate, tetramethylol meta/di.
トリ又はテトラメタクリレートが望ましい。Tri- or tetramethacrylates are preferred.
グリ・ンジルモノビニルエステル又はグリ゛ン・ジルモ
ノビニルエーテル(IL1価アシアルコールリビニルエ
ステル又は多価アルコールノホリヒニルエーテル(It
)との比率は、(■)が多くなると、生成したゲル粒子
の親水性は向上するが、耐圧性は低下する傾向となる。Green glycol monovinyl ester or green glycol monovinyl ether (IL monovalent acyal alcohol ribinyl ester or polyhydric alcohol monovinyl ether
) As the ratio of (■) increases, the hydrophilicity of the generated gel particles improves, but the pressure resistance tends to decrease.
従って、 (I)/(n)の比率は重責比で5015
0〜97/3の範囲であるのが好ましい。Therefore, the ratio of (I)/(n) is 5015 in weight ratio.
It is preferably in the range of 0 to 97/3.
本発明に用いる水と相溶性でない有機溶媒は。The organic solvent that is not miscible with water is used in the present invention.
粒子を多孔性にするために用いられ、これらは25℃で
水100gに対しての溶解量が15g以下のものであり
1例えば、トルエン、ジエチルベンゼン、ドデカン、イ
ソアミルアルコール、クロロベンゼン、酢酸エチル、酢
酸プロピル、酢酸ブチル等がある。これらの溶媒は単独
で用いてもよいし、混合して用いてもよい。溶媒は、単
量体総量に対して50〜300重盪チ使用するのが好ま
しい。水と相溶性でない有機溶媒が少なすぎると。These particles are used to make the particles porous and have a solubility of less than 15 g in 100 g of water at 25° C.1 For example, toluene, diethylbenzene, dodecane, isoamyl alcohol, chlorobenzene, ethyl acetate, propyl acetate. , butyl acetate, etc. These solvents may be used alone or in combination. The solvent is preferably used in an amount of 50 to 300% by weight based on the total amount of monomers. If there are too few organic solvents that are not compatible with water.
得られる粒子を多孔性にし難くなり、多すぎると。Too much will make it difficult to make the resulting particles porous.
得られる粒子の空隙率が大きくなり、耐圧性に乏しくな
る。The resulting particles have a large porosity and poor pressure resistance.
本発明においては、グリシジルモノビニルエステル又は
グリシジルモノビニルエーテル(I)、!=I価アシア
ルコールリビニルエステル又は多価アルコールのポリビ
ニルエーテル(II)とは、水と相溶性でない有機溶媒
の存在下に水性媒体中で懸濁重合させる。In the present invention, glycidyl monovinyl ester or glycidyl monovinyl ether (I),! = I-valent acyal alcohol ribinyl ester or polyvinyl ether of polyhydric alcohol (II) is suspension polymerized in an aqueous medium in the presence of an organic solvent that is not miscible with water.
水性媒体としては、水が使用されるが、懸濁系の安定性
を阻害しない範囲で水性有機溶媒(例えばメタノール、
エタノール、アセトン等)又は無機塩(例えば塩化す)
IJウム、硫酸ナトリウム等)を溶解して含む水を使
用してもよい。なお水性媒体は、前記(I)、 (n
)及び水と相溶しない有機溶媒のinに対して1〜59
重量倍使用するのが好ましbo
このとき、水と相溶性でない有機溶剤の添加時期は9反
応前にすべて添加するか、又は重合率が20%に達する
までに添加するのが好ましい。添加方法としては1分割
して行ってもよい。Water is used as the aqueous medium, but an aqueous organic solvent (e.g. methanol,
ethanol, acetone, etc.) or inorganic salts (e.g. chloride)
Water containing dissolved IJum, sodium sulfate, etc.) may also be used. Note that the aqueous medium is the above (I), (n
) and 1 to 59 for in of organic solvents that are incompatible with water.
It is preferable to use twice the amount by weight. At this time, it is preferable to add all the organic solvents that are not compatible with water before the 9 reactions or until the polymerization rate reaches 20%. The addition method may be divided into one portion.
本発明方法において使用するため好適な懸濁重合の重合
開始剤としては、過酸化ベンゾイル、過酸化ジクロロベ
ンゾイル、過酸化ジクミル、過酸化ジー第三ブチル、2
.5−ジ(ペルオキシベンゾエート)ヘキシン−3,1
,3−ビス−(第三ブチルペルオキシイソプロビル)ベ
ンゼン、 過e化ラウロイル、過酢酸第三ブチル、ス5
−ジメチルース5−ジ(第三ブチルペルオキシ)ヘキシ
ン−3゜2.5−ジメチル−2,5−ジ(第三ブチルペ
ルオキシ)ヘキサン及び過安息香酸第三ブチル、メチル
エチルケトンペルオキシド、メチルシクロヘキサノ/ベ
ルオヤシド等の有機過酸化物、アゾビス−イソブチロニ
トリル及びジメチルアゾジイソブチレート等のアゾ系化
合物があり、これらの1穐又は2種以上を使用できる。Suspension polymerization initiators suitable for use in the process of the invention include benzoyl peroxide, dichlorobenzoyl peroxide, dicumyl peroxide, di-tert-butyl peroxide,
.. 5-di(peroxybenzoate)hexyne-3,1
, 3-bis-(tert-butylperoxyisopropyl)benzene, lauroyl peroxide, tert-butyl peracetate, s5
-dimethylose 5-di(tert-butylperoxy)hexane-3゜2.5-dimethyl-2,5-di(tert-butylperoxy)hexane and tert-butyl perbenzoate, methyl ethyl ketone peroxide, methyl cyclohexano/beroyaside, etc. There are organic peroxides, azo compounds such as azobis-isobutyronitrile, and dimethylazodiisobutyrate, and one or more of these can be used.
この使用量は、ビニル単量体の種類及び得られる重合体
の目的とする分子量によ塾決定されるが、好ましくはビ
ニル系単量体に対して0,1〜4.0重量%使用される
。The amount used is determined depending on the type of vinyl monomer and the desired molecular weight of the resulting polymer, but it is preferably used in an amount of 0.1 to 4.0% by weight based on the vinyl monomer. Ru.
また、@記懸濁重合において2分散剤として難溶性燐酸
塩、水溶性高分子保護コロイド等を重合系に添加するこ
とができる。In addition, in the suspension polymerization mentioned above, sparingly soluble phosphates, water-soluble polymeric protective colloids, etc. can be added to the polymerization system as dispersants.
a溶性燐酸塩としては、燐酸三カルシウム、燐酸マグト
シウム等がある。高分子保護コロイド°としては、ポリ
ビニルアルコール、アルキルセルロース、ヒドロキシア
ルキルセルロース、カルボキンアルキルセルロース等の
水溶性セルロース誘導体、ポリアクII A/酸す)
IJウム等がある。難溶性燐酸塩は2重合系に存在する
物質全量に対して0、O1′ffr量幅以上、水溶性高
分子保護コロイドは10〜o、 o o を重を係の範
囲で使用されるのが好ましい。Examples of a-soluble phosphates include tricalcium phosphate and magtosium phosphate. Polymer protective colloids include polyvinyl alcohol, water-soluble cellulose derivatives such as alkyl cellulose, hydroxyalkyl cellulose, and carboquin alkyl cellulose, and polyac II A/acid).
There are IJum etc. Slightly soluble phosphates are used within the range of 0 to 1'ffr relative to the total amount of substances present in the bipolymerization system, and water-soluble polymeric protective colloids are used within the range of 10 to 1'ffr. preferable.
水性a渭重合を行う場合、水性媒体を除く各成分を予め
混合して又は各々別々に水性媒体に添加して分散させる
ことができる。この場合よく分散させるために、ホモミ
キサー等により高速攪拌するのが好ましく、この高速攪
拌は9重合初期まで行うことができる。これ以後の重合
は、プロペラ攪拌機等を用いる普通の攪拌下に行うこと
ができる。When performing aqueous a-water polymerization, each component except the aqueous medium can be mixed in advance or each component can be added separately to the aqueous medium and dispersed. In this case, in order to disperse well, it is preferable to perform high-speed stirring using a homomixer or the like, and this high-speed stirring can be carried out up to the initial stage of 9-polymerization. The subsequent polymerization can be carried out under ordinary stirring using a propeller stirrer or the like.
粒子(A)のオキシラン環の加水分解は*H酸又は燐酸
を含む水中でオキシラン環を有する共重合体を30〜1
00℃で5〜20時間処理することによりオキシラン環
の約80%を加水分解することができる。Hydrolysis of the oxirane ring of particles (A) is carried out by dissolving the copolymer having an oxirane ring in water containing H acid or phosphoric acid from 30 to 1
Approximately 80% of the oxirane ring can be hydrolyzed by treatment at 00°C for 5 to 20 hours.
オキシラン環を導入するため、水性懸濁重合し次いで加
水分解して得られた粒子(B)に反応させるオキシラン
環を有するアルキルハライドとしては、エビクロルヒド
リ/l エビブロモヒドリ/。In order to introduce an oxirane ring, the alkyl halide having an oxirane ring to be reacted with the particles (B) obtained by aqueous suspension polymerization and subsequent hydrolysis is shrimp chlorohydrin/l shrimp bromohydrin/.
エビフルオルヒドリン、エビヨードヒドリンが挙げられ
る。これらの化合物は、水酸化ナトリウム。Examples include shrimp fluorohydrin and shrimp iodohydrin. These compounds are sodium hydroxide.
水酸化カリウム等の水酸化物の存在下に、ジメチルスル
ホキシド、 N、N−ジメチルホルムアミド。Dimethyl sulfoxide, N,N-dimethylformamide in the presence of a hydroxide such as potassium hydroxide.
N、N−ジメチルアセトアミド等の極性溶媒中で粒子(
B)を膨潤させて反応させることができる。Particles (
B) can be swollen and reacted.
オキシラン環を有するアルキルハライドは、良く乾燥し
た多孔性架橋重合体粒子1g当たり10′″6モル以上
使用するのが好ましい。The alkyl halide having an oxirane ring is preferably used in an amount of 10''6 mol or more per gram of well-dried porous crosslinked polymer particles.
1g当たり104モル未満の使用である場合。If less than 104 moles per gram are used.
粒子(B)に付与されるオキシラン環(次のグラフト重
合の反応開始点)の濃度が低く、新水性を向上させる効
果が少なくなる傾向がある。The concentration of the oxirane ring (reaction starting point for the next graft polymerization) imparted to the particles (B) is low, and the effect of improving fresh water properties tends to be reduced.
水酸化す) IJウム、水酸化カリウム等の水酸化物は
、オキシラン環を有するアルキルハライドに対して等モ
ル以上あれば良く、ジメチルスルホキシド、 N、N
−ジメチルホルムアミド、 N、N−ジメチルアセトア
ミド等の極性溶媒は9反応系を攪拌できるのに充分な1
1あれば良く、特に制限はない。The amount of hydroxide such as IJium or potassium hydroxide may be at least equimolar to the alkyl halide having an oxirane ring, and dimethyl sulfoxide, N, N, etc.
- Polar solvents such as dimethylformamide, N,N-dimethylacetamide, etc. should be used at a concentration of 1 to 90% to stir the reaction system.
1 is sufficient, and there is no particular restriction.
反応は30−100℃の範囲で1時間以上行うことが好
ましくへ。The reaction is preferably carried out at a temperature in the range of 30-100°C for 1 hour or more.
このようKして得られるオキシラン環を有する粒子(C
)は、核粒子1g当たり、オキシラン基0.1〜2me
q有するように調整されるのが好ましい。この値が小さ
すぎると1次の1糧において。Particles having oxirane rings (C
) is 0.1 to 2 me of oxirane group per 1 g of core particles.
It is preferable to adjust it so that it has q. If this value is too small, it will cause problems in the first food.
オキシラ/環を有する化合物を充分グラフトさせること
ができず、多すぎると、オキシラン環の導入は、困難で
ある。If the oxirane/ring-containing compound cannot be grafted sufficiently, and if the amount is too large, it will be difficult to introduce the oxirane ring.
なお、水性懸濁重合し、加水分解して得られた粒子(B
)のオキシラ/環を有するアルキルハライドとの反応点
は、該粒子(B)中に存在する水酸基である。In addition, particles obtained by aqueous suspension polymerization and hydrolysis (B
The point of reaction with the alkyl halide having an oxira/ring in ) is the hydroxyl group present in the particle (B).
オキシラン環が導入された粒子(C)にグラフト重合さ
せる。オキシラン環を有する化合物としては、充分な親
水性を有することが必要であり、親水性基、すなわち水
酸基やエーテル基を多く含有しているものが望ましく、
マた。共重合反応によって、細孔表面が親水性の側鎖で
覆われるように一定数以上のオキシラ/環を有している
ことが好ましい。The particles (C) into which the oxirane ring has been introduced are subjected to graft polymerization. The compound having an oxirane ring must have sufficient hydrophilicity, and it is desirable that the compound contains a large amount of hydrophilic groups, that is, hydroxyl groups and ether groups.
Mata. It is preferable to have a certain number or more of oxiras/rings so that the pore surfaces are covered with hydrophilic side chains through a copolymerization reaction.
また、オキシラン環を有する化合物の分子量が大きすぎ
ると、最終的に得られる多孔性の架橋重合体粒子内の細
孔容積を減少させるので、好ましくない。Further, if the molecular weight of the compound having an oxirane ring is too large, the pore volume in the finally obtained porous crosslinked polymer particles is decreased, which is not preferable.
このため9本発明に使用する。オキシラン環を有する化
合物としては、水への溶解度が29/100m1!水(
25℃)以上1分子量1000以下で、かつエポキシ基
当量(分子量/オキシラン環の数)が300以下のもの
が好ましく1例えばエチレンオキシド、グリシドール、
1.2.34−ジェポキシブタン、ジグリシジルエーテ
ル、エチレングリコール(モノ−若しくはジ)グリシジ
ルエーテル、グリセリンポリグリシジルエーテル、ソル
ビットポリグリシジルエーテル、ジグリセロールボリグ
リシジルエーテル、ポリエチレングリコール(七ノー若
しくはジ)グリシジルエーテル(ポリエチレングリコー
ルの重合度9以下)、ポリプロピレングリコール(モノ
−若しくはジ)グリシジルエーテル(ポリプロピレング
リコールの重合度3以下)、1.4−ブタンジオール(
モノ−若しくはジ)グリシジルエーテル、1.3−7’
0パンジオール(七ノー若しくはジ)グリシジルエーテ
ル等が挙げられる。For this reason, 9 are used in the present invention. As a compound with an oxirane ring, the solubility in water is 29/100ml! water(
25°C) or more and 1,000 or less, and an epoxy group equivalent (molecular weight/number of oxirane rings) of 300 or less. For example, ethylene oxide, glycidol,
1.2.34-Jepoxybutane, diglycidyl ether, ethylene glycol (mono- or di)glycidyl ether, glycerin polyglycidyl ether, sorbitol polyglycidyl ether, diglycerol polyglycidyl ether, polyethylene glycol (7- or di)glycidyl ether ( (polymerization degree of polyethylene glycol 9 or less), polypropylene glycol (mono- or di)glycidyl ether (polymerization degree of polypropylene glycol 3 or less), 1,4-butanediol (
Mono- or di)glycidyl ether, 1.3-7'
Examples include 0-panediol (7-no or di)glycidyl ether.
これらの化合物のグラフト看は、前記のオキシラン環が
導入された粒子(C)igに対して0.05〜IgKな
るように調整されるのが好ましい。グラフト量が多すぎ
ると、最終的に得られた粒子の膨潤度が増し、該粒子を
カラムに詰めて分析を行う場合にカラム圧を高くしなけ
ればならず、該粒子の破壊が起こりやすぐなる。グラフ
ト量が少なすぎると、オキシラン環を有する化合物をグ
ラフトさせることによる親水性の付与効果が小さくなる
傾向となる。The graft density of these compounds is preferably adjusted to be 0.05 to IgK relative to the particle (C)ig into which the oxirane ring is introduced. If the amount of grafting is too large, the degree of swelling of the final particles will increase, and when the particles are packed in a column for analysis, the column pressure must be increased, and the particles are likely to be destroyed. Become. If the amount of grafting is too small, the effect of imparting hydrophilicity by grafting the compound having an oxirane ring will tend to be reduced.
グラフト重合に使用される触媒としては、硫酸。Sulfuric acid is used as a catalyst for graft polymerization.
塩酸、過塩素酸、燐酸等のプロトン酸、三弗化硼素、三
弗化硼素エーテラート、四弗化硼素亜鉛等のルイス酸及
び塩化第一錫、塩化第二錫、四塩化チタン、塩化アルミ
ニウム等の金属ハロゲン化物等が挙げられるが、特に三
弗化硼素エーテラートが好ましい。また、触媒の使用量
は、オキシラン環を有する化合物に対して0.01〜3
0重量%であるのが好ましい。Protonic acids such as hydrochloric acid, perchloric acid, and phosphoric acid; Lewis acids such as boron trifluoride, boron trifluoride etherate, and zinc boron tetrafluoride; and stannous chloride, tin chloride, titanium tetrachloride, aluminum chloride, etc. Among them, boron trifluoride etherate is particularly preferred. In addition, the amount of catalyst used is 0.01 to 3 for the compound having an oxirane ring.
Preferably it is 0% by weight.
グラフト重合を実施する際には、溶媒の存在は必須では
な(へが9表面の均一性や操作性の点から。When carrying out graft polymerization, the presence of a solvent is not essential (from the viewpoint of surface uniformity and operability).
通常、溶媒の存在下で反応を行う方が有利である。It is usually advantageous to carry out the reaction in the presence of a solvent.
溶媒としては9粒子(C)やオキシラン環を有する化合
物に対して不活性であればよく、脂肪族又は脂環式のエ
ーテル類、ケトン類、エステル類、炭化水素類、ハロゲ
ン化炭化水素類、ニトリル類。The solvent may be inert to the 9 particles (C) or the compound having an oxirane ring, and may include aliphatic or alicyclic ethers, ketones, esters, hydrocarbons, halogenated hydrocarbons, Nitriles.
スルホキ7ド類等を挙げることができる。特に好ましく
へ溶媒としては、エチルエーテル、ジエチレンクリコー
ルジメチルエーテル、エチレングリコールジブチルエー
テル、テトラヒドロフラン、1゜4−ジオキサン等のエ
ーテル類、1.2−ジクロロエタン、1.4−ジブロモ
エタン、1.2−ジクロロ’jc1ハフ、 1.1.
2− トリクロロエタン等のハロゲン化炭化水素類、ジ
メチルスルホキシド等のスルホキ7ド類等を挙げること
ができる。Examples include sulfokides and the like. Particularly preferred solvents include ethers such as ethyl ether, diethylene glycol dimethyl ether, ethylene glycol dibutyl ether, tetrahydrofuran, 1°4-dioxane, 1.2-dichloroethane, 1.4-dibromoethane, 1.2-dichloroethane, etc. 'jc1 Hough, 1.1.
Examples include halogenated hydrocarbons such as 2-trichloroethane, sulfoxides such as dimethyl sulfoxide, and the like.
グラフト重合は、低温でも反応速度が速いものもあるが
、一般忙は、低温では反応速度が遅くなり、実用性に乏
しく、逆に高温では9種々の最適な反応湯度は、オキシ
ラ/環を有する化合物の稽類、溶媒の種類、触媒の種類
等によって選択されるが9通常、0〜150℃の範囲で
ある。Some graft polymerizations have a fast reaction rate even at low temperatures, but in general, the reaction rate slows down at low temperatures, making them impractical; on the other hand, at high temperatures, the various optimal reaction temperatures are Although the temperature is selected depending on the type of compound, the type of solvent, the type of catalyst, etc., the temperature is usually in the range of 0 to 150°C.
以上のようにして得゛られた球状粒子は9粒径1〜50
μm、好ましくは1〜15μmに分級し。The spherical particles obtained in the above manner had 9 particle sizes of 1 to 50.
Classified into μm, preferably 1 to 15 μm.
ゲルパーミニ−7ヨンクロマトグラフイー用又は分配吸
着型クロマトグラフィー用充填剤として使用することが
できる。更に、イオン交換基、グリ7ジル基、長鎖アル
キル基等を導入して、充填剤としての性質を変えたり、
アフイニテイクロマトグラフイーやイオン交換クロマト
グラフィー用担体としても使用可能である。It can be used as a packing material for gel permini-7 chromatography or partition adsorption chromatography. Furthermore, by introducing ion exchange groups, glycidyl groups, long chain alkyl groups, etc., the properties as fillers can be changed.
It can also be used as a carrier for affinity chromatography and ion exchange chromatography.
グリシジルモノビニルエステル又はグリシジルモノビニ
ルエーテル(1)と多価アルコールのポリビニルエステ
ル又は多価アルコールのポリビニルエーテル(II)を
、水と相溶性でない有機溶媒(1)の存在下で水性懸濁
重合させ、更に、得られた粒子(A)の(I)Ilii
分に基づくオキシラン環を水によって加水分解させると
、得られる粒子(B)は親水性及び耐圧性を兼ね備えた
本のとなる。Glycidyl monovinyl ester or glycidyl monovinyl ether (1) and polyvinyl ester of polyhydric alcohol or polyvinyl ether of polyhydric alcohol (II) are subjected to aqueous suspension polymerization in the presence of an organic solvent (1) that is not miscible with water, and further , (I)Ilii of the obtained particles (A)
When the oxirane ring based on the compound is hydrolyzed with water, the resulting particles (B) have both hydrophilicity and pressure resistance.
また9粒子(B)にアルキルハライドを反応させること
により得られた粒子(C)にオキシラン環を有する化合
物をグラフト重合させることにより。Also, by graft polymerizing a compound having an oxirane ring to particles (C) obtained by reacting 9 particles (B) with an alkyl halide.
更に親水性が増加した最終生成物の架橋重合体粒子を得
ることができる。Further, crosslinked polymer particles of the final product with increased hydrophilicity can be obtained.
(実施例) 次に、実施例に基づいて本発明を詳述するが。(Example) Next, the present invention will be explained in detail based on examples.
本発明はこれに限定されるものではない。The present invention is not limited to this.
実施例1
(1)水性懸濁重合による粒子(A)及びそれを用いた
粒子(B)の製造
エチレングリコールジメタクリレー) 409゜グリ7
ジルメタクリレート1609.酢酸n−ブチル75g、
イソアミルアルコール125g及びアゾビスイソブチロ
ニトリル1.0gの混合物を水1760m1!に加え、
ホモミキサーを使用して高速攪拌しながら室温で1%メ
チルセルロース水溶液200m1!を逐次添加し1粒径
を調節した後。Example 1 (1) Production of particles (A) and particles (B) using the same by aqueous suspension polymerization Ethylene glycol dimethacrylate) 409°Gly7
Zil methacrylate 1609. 75g n-butyl acetate,
A mixture of 125g of isoamyl alcohol and 1.0g of azobisisobutyronitrile was added to 1760ml of water! In addition to
200ml of 1% methylcellulose aqueous solution at room temperature with high speed stirring using a homomixer! was added sequentially to adjust the particle size.
1チメチルセルロース水溶液220 mJを予め加えた
31の7、ラスコに移し、85℃で6時間懸濁重合させ
た。The mixture was transferred to a 31-7 flask to which 220 mJ of 1-thimethylcellulose aqueous solution had been added in advance, and suspension polymerization was carried out at 85° C. for 6 hours.
得られた粒子(A)全量を0.5N硫酸中80℃で反応
させて、オキシラン環を加水分解させて粒子(B)を得
た。The entire amount of the obtained particles (A) was reacted in 0.5N sulfuric acid at 80°C to hydrolyze the oxirane ring to obtain particles (B).
(2)オキラン環の導入による粒子(C)の製造(1)
で合成し、8〜15μmに分級した粒子(B)25g、
エピクロルヒドリン17411s ジメチルスルホキ
シド225 ml及び30m水酸化ナトリウム水溶液1
8gをII!のフラスコに仕込み。(2) Production of particles (C) by introducing ocilane rings (1)
25 g of particles (B) synthesized and classified into 8 to 15 μm,
Epichlorohydrin 17411s dimethyl sulfoxide 225 ml and 30 m sodium hydroxide aqueous solution 1
8g II! Prepared in a flask.
40℃で6時間反応させた。反応後9口過して粒子ヲ集
め、順次、ジメチルスルホキシド、水及びアセトンで洗
浄して、オキシラン環を有する粒子(C)を得た。The reaction was carried out at 40°C for 6 hours. After the reaction, the particles were collected after 9 passes and washed successively with dimethyl sulfoxide, water and acetone to obtain particles (C) having an oxirane ring.
塩酸・塩化カルシウム法でオキシラン環を定量したとこ
ろ、1.tmeq/gであった。When the oxirane ring was quantified using the hydrochloric acid/calcium chloride method, 1. It was tmeq/g.
(3)グラフト重合
(2)で合成したオキシラン環を有する粒子(C)50
g、エチレングリコールジグリシジルエーテル(水への
溶解度Log/100m1!水、25℃)50g、三弗
化硼素エチルエーテル錯体5ml及び1.4−ジオキサ
ン500m1!を11!のフラスコに仕込み、80℃で
5時間反応させグラフト重合を行った。反応後、生成粒
子を口過して集め、順次、1.4−ジオキサン及びアセ
トンで洗浄し。(3) Particles having oxirane rings synthesized by graft polymerization (2) (C) 50
g, 50 g of ethylene glycol diglycidyl ether (solubility in water Log/100 ml! water, 25°C), 5 ml of boron trifluoride ethyl ether complex and 500 ml of 1,4-dioxane! 11! The mixture was charged into a flask and reacted at 80°C for 5 hours to perform graft polymerization. After the reaction, the produced particles were collected by sieving and washed sequentially with 1,4-dioxane and acetone.
60℃で3時間、減圧乾燥した。得られた架橋重合体粒
子は多孔性で、その収量は、sa、7gであった。It was dried under reduced pressure at 60°C for 3 hours. The obtained crosslinked polymer particles were porous and the yield was sa, 7 g.
(4)応用
こうして得られた粒子をふるい分けして8〜15μmの
粒度とし、直径8.0ms高さ30〇−のステンレスカ
ラムに充填した。このカラムを用いて蛋白質、アミノ酸
の測定を行った。測定条件は、移動相に0.5Mの塩化
ナトリウムを含む20mM燐酸緩衝液(pH7)、流量
を1.0ml!/分。(4) Application The particles thus obtained were sieved to a particle size of 8 to 15 μm and packed into a stainless steel column with a diameter of 8.0 ms and a height of 300 mm. Proteins and amino acids were measured using this column. The measurement conditions were a mobile phase of 20mM phosphate buffer (pH 7) containing 0.5M sodium chloride, and a flow rate of 1.0ml! /min.
温度を25℃とし、検出器にはUV検出器(280nm
)を使用した。The temperature was 25°C, and the detector was a UV detector (280 nm
)It was used.
蛋白質(チログロブリン、T−グロブリン、牛血清アル
ブミン、卵白アルブミン、α−キモトリプシノーゲン、
チトクロームC,インシュリン。Proteins (thyroglobulin, T-globulin, bovine serum albumin, ovalbumin, α-chymotrypsinogen,
Cytochrome C, insulin.
β−アラニン)の分子量と溶出容量との関係を示した(
交正曲線を第1図に示した。符号1〜8は。The relationship between the molecular weight of β-alanine) and the elution volume (
The intersection curves are shown in Figure 1. Codes 1 to 8 are.
頑次、上記の記載順の物質のプロットである。This is a plot of the substances in the order listed above.
実施例2
実施例1の(2)で合成したオキシラン環を有する粒子
(C)509.グリシドールsog、三弗化硼素エチル
エーテル錯体5ml!及びL4−ジオキサ7500 m
lを11!のフラスコに仕込み、80℃で5時間反応さ
せグラフト重合を行った。反応後。Example 2 Particles (C) 509. having an oxirane ring synthesized in Example 1 (2). Glycidol sog, boron trifluoride ethyl ether complex 5ml! and L4-dioxa 7500 m
11 l! The mixture was charged into a flask and reacted at 80°C for 5 hours to perform graft polymerization. After reaction.
生成粒子を口過して集め、順次、1.4−ジオキサン及
びアセトンで洗浄し、60℃で3時間、減圧乾燥した。The produced particles were collected by filtration, sequentially washed with 1,4-dioxane and acetone, and dried under reduced pressure at 60° C. for 3 hours.
得られた架橋重合体粒子は多孔性で。The resulting crosslinked polymer particles are porous.
その収量は、63.59であった。The yield was 63.59.
こうして得られた粒子をふるい分けして8〜15μmの
粒度とし、直径8.0am+e高さ300#のステンレ
スカラムに充填した。このカラムを用いて蛋白質、アミ
ノ酸の測定を行った。測定条件は、移動相に0.5Mの
塩化ナトリウムを含む20mM燐酸緩衝液(pH7)、
流量を1.0mj’/分。The particles thus obtained were sieved to a particle size of 8-15 μm and packed into a stainless steel column with a diameter of 8.0 am+e and a height of 300#. Proteins and amino acids were measured using this column. The measurement conditions were: 20mM phosphate buffer (pH 7) containing 0.5M sodium chloride in the mobile phase;
The flow rate was 1.0 mj'/min.
温度を25℃とし、検出器に:FiUV検出器(280
nm)を使用した。The temperature was set to 25°C, and the detector was a FiUV detector (280
nm) was used.
蛋白質(実施例1と同様)の分子量と溶出容量との関係
を示した較正曲線を第2図に示した。符号9〜16は、
順次、前記の記載順の物質のプロットである。A calibration curve showing the relationship between the molecular weight of the protein (same as in Example 1) and the elution volume is shown in FIG. Codes 9 to 16 are
Sequentially, the substances are plotted in the order listed above.
比較例
実施例1の(1)で合成した粒子(B)をふるい分けし
て8〜15μmの粒度とし、直径& Off1b高さ3
00mmのステンレスカラムに充填した。このカラムを
用いて省白質、アミノ酸の測定を行った。Comparative Example The particles (B) synthesized in Example 1 (1) were sieved to have a particle size of 8 to 15 μm, and the diameter & Off1b height was 3.
It was packed into a 00 mm stainless steel column. This column was used to measure white matter and amino acids.
測定条件は、移動相に0.5Mの塩化す) 13ウムを
詮む20mM燐酸緩衝液(pH7)、流量を1.0ml
!/分、温度を25℃とし、検出器にはUV検出器(2
80nm >を使用した。The measurement conditions were: 20mM phosphate buffer (pH 7) containing 13 um (0.5M chloride in the mobile phase), and a flow rate of 1.0ml.
! /min, the temperature was 25℃, and the detector was equipped with a UV detector (2
80 nm> was used.
蛋白質(実施例1と同様)の分子量と溶出容量との関係
を示した較正曲線を第3図に示した。符号17〜24は
、順次+ m記の記載順の物質のプロットである。A calibration curve showing the relationship between the molecular weight of the protein (same as in Example 1) and the elution volume is shown in FIG. Reference numerals 17 to 24 are plots of substances in the order of +m.
(発明の効果)
本発明によれば、耐圧性及び親水性に優れた多孔性の球
状の粒子が得られ、この多孔性の架橋重合体粒子は、液
体クロマトグラフィー用充填剤又は液体クロマトグラフ
ィー用充填剤合成用の中間体として好適である。(Effects of the Invention) According to the present invention, porous spherical particles with excellent pressure resistance and hydrophilicity can be obtained, and these porous crosslinked polymer particles can be used as a filler for liquid chromatography or as a filler for liquid chromatography. Suitable as an intermediate for filler synthesis.
第1図は、実施例1において測定した較正曲線。
第2図は、実施例2において測定した較正曲線。
第3図は、比較例において測定した較正曲線である。
符号の説明
1・・・チログロブリン 2・・・γ−グロブリン3・
・・牛血清アルブミ/ 4・・・卵白アルブミン5・・
・α−キモトリプシノーゲン
6・・・チトクロームC7・・・インシュリン8・・・
β−アラニン 9・・・チログロブリン10・・・γ
−グロブリン 11・・・牛血清アルブミン12・・・
卵白アルブミン
13・・・α−キモトリプシノーゲン
14・・・チトクロームC15・・・インシュリン16
・・・β−アラニン 17・・・チログロブリン18・
・・γ−グロブリン19・・・牛血清アルブミン20・
・・卵白アルブミン
21・・・α−キモトリプシノーゲン
22・・・チトクロームC23・・・インシュリン24
・・・β・・・アラニン
溶出容1(■勾
罰 1 図
り芝呼 主 43二 量 師ツノ第 2 図FIG. 1 is a calibration curve measured in Example 1. FIG. 2 is a calibration curve measured in Example 2. FIG. 3 is a calibration curve measured in a comparative example. Explanation of symbols 1... Thyroglobulin 2... γ-globulin 3.
...Bovine serum albumin/4...Ovalbumin5...
・α-chymotrypsinogen 6...Cytochrome C7...Insulin 8...
β-alanine 9...Thyroglobulin 10...γ
-Globulin 11...Bovine serum albumin 12...
Ovalbumin 13...α-chymotrypsinogen 14...Cytochrome C15...Insulin 16
...β-Alanine 17... Thyroglobulin 18.
・・γ-globulin 19・・bovine serum albumin 20・
・・Ovalbumin 21・α-chymotrypsinogen 22・Cytochrome C23・Insulin 24
...β...Alanine elution volume 1 (■ Punishment 1 Figure 432 Volume Master Tsuno 2
Claims (1)
ビニルエーテル( I )と多価アルコールのポリビニル
エステル又は多価アルコールのポリビニルエーテル(I
I)を、水と相溶性でない有機溶媒(III)の存在下で水
性懸濁重合させ、更に、得られた粒子(A)の( I )
成分によるオキシラン環を加水分解させ、更に、得られ
た粒子(B)にオキシラン環を有するアルキルハライド
を反応させてオキシラン環を導入し、このオキシラン環
を有する粒子(C)のオキシラン環にオキシラン環を有
する化合物をグラフト重合させることを特徴とする架橋
重合体粒子の製造法。 2、グリシジルモノビニルエステル又はグリシジルモノ
ビニルエーテル( I )と多価アルコールのポリビニル
エステル又は多価アルコールのポリビニルエーテル(I
I)の重量比を50/50〜97/3とする請求項1記
載の製造法。 3、成分( I )がグリシジルメタクリレートである請
求項1又は2記載の製造法。 4、オキシラン環を有する化合物が、水への溶解度が2
g/100ml水(25℃)以上であり、分子量100
0以下で、エポキシ当量(分子量/オキシラン環の数)
が300以下の化合物である請求項1、2又は3記載の
製造法。[Scope of Claims] 1. Glycidyl monovinyl ester or glycidyl monovinyl ether (I) and polyvinyl ester of polyhydric alcohol or polyvinyl ether of polyhydric alcohol (I)
I) is subjected to aqueous suspension polymerization in the presence of an organic solvent (III) that is not miscible with water, and further, (I) of the obtained particles (A) is
The oxirane ring caused by the component is hydrolyzed, and the obtained particles (B) are further reacted with an alkyl halide having an oxirane ring to introduce an oxirane ring, and the oxirane ring is added to the oxirane ring of the particle (C) having this oxirane ring. 1. A method for producing crosslinked polymer particles, the method comprising graft polymerizing a compound having the following. 2. Glycidyl monovinyl ester or glycidyl monovinyl ether (I) and polyvinyl ester of polyhydric alcohol or polyvinyl ether of polyhydric alcohol (I)
2. The method according to claim 1, wherein the weight ratio of I) is 50/50 to 97/3. 3. The manufacturing method according to claim 1 or 2, wherein component (I) is glycidyl methacrylate. 4. A compound with an oxirane ring has a solubility in water of 2.
g/100ml water (25℃) or more, molecular weight 100
0 or less, epoxy equivalent (molecular weight/number of oxirane rings)
4. The method according to claim 1, 2 or 3, wherein the compound has a compound of 300 or less.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP63044832A JPH01217035A (en) | 1988-02-26 | 1988-02-26 | Production of crosslinked polymer particle |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP63044832A JPH01217035A (en) | 1988-02-26 | 1988-02-26 | Production of crosslinked polymer particle |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH01217035A true JPH01217035A (en) | 1989-08-30 |
Family
ID=12702438
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP63044832A Pending JPH01217035A (en) | 1988-02-26 | 1988-02-26 | Production of crosslinked polymer particle |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH01217035A (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003029327A1 (en) * | 2001-09-28 | 2003-04-10 | Showa Denko K. K. | Particulate hydrophobic polymer, production process therefor and column for reversed-phase high-performance liquid chromatography |
WO2007142331A1 (en) * | 2006-06-08 | 2007-12-13 | Reverse Proteomics Research Institute Co., Ltd. | Affinity carrier and method for production thereof |
WO2011125674A1 (en) * | 2010-03-31 | 2011-10-13 | Jsr株式会社 | Filler for affinity chromatography |
WO2013187512A1 (en) * | 2012-06-15 | 2013-12-19 | 旭化成メディカル株式会社 | Alkali-resistant ion exchange temperature-responsive adsorbent, and method for producing same |
-
1988
- 1988-02-26 JP JP63044832A patent/JPH01217035A/en active Pending
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003029327A1 (en) * | 2001-09-28 | 2003-04-10 | Showa Denko K. K. | Particulate hydrophobic polymer, production process therefor and column for reversed-phase high-performance liquid chromatography |
US7205361B2 (en) * | 2001-09-28 | 2007-04-17 | Showa Denko K.K. | Particulate hydrophobic polymer, production process therefor and column for reversed-phase high-performance liquid chromatography |
WO2007142331A1 (en) * | 2006-06-08 | 2007-12-13 | Reverse Proteomics Research Institute Co., Ltd. | Affinity carrier and method for production thereof |
WO2011125674A1 (en) * | 2010-03-31 | 2011-10-13 | Jsr株式会社 | Filler for affinity chromatography |
US9162161B2 (en) | 2010-03-31 | 2015-10-20 | Jsr Corporation | Filler for affinity chromatography |
JP5998050B2 (en) * | 2010-03-31 | 2016-09-28 | Jsr株式会社 | Affinity chromatography packing |
WO2013187512A1 (en) * | 2012-06-15 | 2013-12-19 | 旭化成メディカル株式会社 | Alkali-resistant ion exchange temperature-responsive adsorbent, and method for producing same |
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