JPH0510626B2 - - Google Patents
Info
- Publication number
- JPH0510626B2 JPH0510626B2 JP58147364A JP14736483A JPH0510626B2 JP H0510626 B2 JPH0510626 B2 JP H0510626B2 JP 58147364 A JP58147364 A JP 58147364A JP 14736483 A JP14736483 A JP 14736483A JP H0510626 B2 JPH0510626 B2 JP H0510626B2
- Authority
- JP
- Japan
- Prior art keywords
- microcapsules
- diisocyanate
- physiological saline
- antibody
- diluted
- 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
- 239000003094 microcapsule Substances 0.000 claims description 54
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 16
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 16
- 239000000243 solution Substances 0.000 claims description 14
- 239000000126 substance Substances 0.000 claims description 14
- -1 amino compound Chemical class 0.000 claims description 11
- 239000012948 isocyanate Substances 0.000 claims description 9
- 150000002513 isocyanates Chemical class 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 229920000172 poly(styrenesulfonic acid) Polymers 0.000 claims description 7
- 229940005642 polystyrene sulfonic acid Drugs 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000006185 dispersion Substances 0.000 claims description 4
- 230000000379 polymerizing effect Effects 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 30
- 239000002504 physiological saline solution Substances 0.000 description 21
- 238000000034 method Methods 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 11
- 239000002953 phosphate buffered saline Substances 0.000 description 10
- 239000000427 antigen Substances 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- 238000001514 detection method Methods 0.000 description 8
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 7
- 229940098773 bovine serum albumin Drugs 0.000 description 7
- 238000005119 centrifugation Methods 0.000 description 7
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000006116 polymerization reaction Methods 0.000 description 6
- 239000011162 core material Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 230000004520 agglutination Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000004816 latex Substances 0.000 description 4
- 229920000126 latex Polymers 0.000 description 4
- 229960003646 lysine Drugs 0.000 description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- DVKJHBMWWAPEIU-UHFFFAOYSA-N toluene 2,4-diisocyanate Chemical compound CC1=CC=C(N=C=O)C=C1N=C=O DVKJHBMWWAPEIU-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- 239000005057 Hexamethylene diisocyanate Substances 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 150000004985 diamines Chemical class 0.000 description 3
- 230000001804 emulsifying effect Effects 0.000 description 3
- RRAMGCGOFNQTLD-UHFFFAOYSA-N hexamethylene diisocyanate Chemical compound O=C=NCCCCCCN=C=O RRAMGCGOFNQTLD-UHFFFAOYSA-N 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 238000007127 saponification reaction Methods 0.000 description 3
- IAUKWGFWINVWKS-UHFFFAOYSA-N 1,2-di(propan-2-yl)naphthalene Chemical compound C1=CC=CC2=C(C(C)C)C(C(C)C)=CC=C21 IAUKWGFWINVWKS-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- 241000589902 Leptospira Species 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 239000010775 animal oil Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 125000005442 diisocyanate group Chemical group 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- TZMQHOJDDMFGQX-UHFFFAOYSA-N hexane-1,1,1-triol Chemical compound CCCCCC(O)(O)O TZMQHOJDDMFGQX-UHFFFAOYSA-N 0.000 description 2
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 150000002540 isothiocyanates Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000005056 polyisocyanate Substances 0.000 description 2
- 229920001228 polyisocyanate Polymers 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- MGNBKNBEZGLHNF-UHFFFAOYSA-N (2-methylpyrazol-3-yl)boronic acid Chemical compound CN1N=CC=C1B(O)O MGNBKNBEZGLHNF-UHFFFAOYSA-N 0.000 description 1
- XBTRYWRVOBZSGM-UHFFFAOYSA-N (4-methylphenyl)methanediamine Chemical compound CC1=CC=C(C(N)N)C=C1 XBTRYWRVOBZSGM-UHFFFAOYSA-N 0.000 description 1
- FKTHNVSLHLHISI-UHFFFAOYSA-N 1,2-bis(isocyanatomethyl)benzene Chemical compound O=C=NCC1=CC=CC=C1CN=C=O FKTHNVSLHLHISI-UHFFFAOYSA-N 0.000 description 1
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- VGHSXKTVMPXHNG-UHFFFAOYSA-N 1,3-diisocyanatobenzene Chemical compound O=C=NC1=CC=CC(N=C=O)=C1 VGHSXKTVMPXHNG-UHFFFAOYSA-N 0.000 description 1
- IKYNWXNXXHWHLL-UHFFFAOYSA-N 1,3-diisocyanatopropane Chemical compound O=C=NCCCN=C=O IKYNWXNXXHWHLL-UHFFFAOYSA-N 0.000 description 1
- ALQLPWJFHRMHIU-UHFFFAOYSA-N 1,4-diisocyanatobenzene Chemical compound O=C=NC1=CC=C(N=C=O)C=C1 ALQLPWJFHRMHIU-UHFFFAOYSA-N 0.000 description 1
- SIZPGZFVROGOIR-UHFFFAOYSA-N 1,4-diisocyanatonaphthalene Chemical compound C1=CC=C2C(N=C=O)=CC=C(N=C=O)C2=C1 SIZPGZFVROGOIR-UHFFFAOYSA-N 0.000 description 1
- PWGJDPKCLMLPJW-UHFFFAOYSA-N 1,8-diaminooctane Chemical compound NCCCCCCCCN PWGJDPKCLMLPJW-UHFFFAOYSA-N 0.000 description 1
- VYOWNYLBHHBVDR-UHFFFAOYSA-N 1-(3-methylbutyl)-2-phenylbenzene Chemical group CC(C)CCC1=CC=CC=C1C1=CC=CC=C1 VYOWNYLBHHBVDR-UHFFFAOYSA-N 0.000 description 1
- CVAMMFFQVDUIEX-UHFFFAOYSA-N 1-benzyl-2,4-dimethylbenzene Chemical compound CC1=CC(C)=CC=C1CC1=CC=CC=C1 CVAMMFFQVDUIEX-UHFFFAOYSA-N 0.000 description 1
- DTZHXCBUWSTOPO-UHFFFAOYSA-N 1-isocyanato-4-[(4-isocyanato-3-methylphenyl)methyl]-2-methylbenzene Chemical compound C1=C(N=C=O)C(C)=CC(CC=2C=C(C)C(N=C=O)=CC=2)=C1 DTZHXCBUWSTOPO-UHFFFAOYSA-N 0.000 description 1
- HKTCLPBBJDIBGF-UHFFFAOYSA-N 1-phenyl-2-propan-2-ylbenzene Chemical group CC(C)C1=CC=CC=C1C1=CC=CC=C1 HKTCLPBBJDIBGF-UHFFFAOYSA-N 0.000 description 1
- VILCJCGEZXAXTO-UHFFFAOYSA-N 2,2,2-tetramine Chemical compound NCCNCCNCCN VILCJCGEZXAXTO-UHFFFAOYSA-N 0.000 description 1
- XHLFUMPVVXAFKO-UHFFFAOYSA-N 2,2-bis[(3-isocyanato-4-methylphenyl)carbamoyloxymethyl]butyl n-(3-isocyanato-4-methylphenyl)carbamate Chemical compound C=1C=C(C)C(N=C=O)=CC=1NC(=O)OCC(COC(=O)NC=1C=C(C(C)=CC=1)N=C=O)(CC)COC(=O)NC1=CC=C(C)C(N=C=O)=C1 XHLFUMPVVXAFKO-UHFFFAOYSA-N 0.000 description 1
- KKTUQAYCCLMNOA-UHFFFAOYSA-N 2,3-diaminobenzoic acid Chemical compound NC1=CC=CC(C(O)=O)=C1N KKTUQAYCCLMNOA-UHFFFAOYSA-N 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- MQIUGAXCHLFZKX-UHFFFAOYSA-N Di-n-octyl phthalate Natural products CCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCC MQIUGAXCHLFZKX-UHFFFAOYSA-N 0.000 description 1
- RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical compound NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 206010024238 Leptospirosis Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- SPTUBPSDCZNVSI-UHFFFAOYSA-N N=C=O.N=C=O.COC1=CC=CC=C1C1=CC=CC=C1OC Chemical compound N=C=O.N=C=O.COC1=CC=CC=C1C1=CC=CC=C1OC SPTUBPSDCZNVSI-UHFFFAOYSA-N 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- RMUCZJUITONUFY-UHFFFAOYSA-N Phenelzine Chemical compound NNCCC1=CC=CC=C1 RMUCZJUITONUFY-UHFFFAOYSA-N 0.000 description 1
- 206010035148 Plague Diseases 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000004984 aromatic diamines Chemical class 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- BJQHLKABXJIVAM-UHFFFAOYSA-N bis(2-ethylhexyl) phthalate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1C(=O)OCC(CC)CCCC BJQHLKABXJIVAM-UHFFFAOYSA-N 0.000 description 1
- OMWQUXGVXQELIX-UHFFFAOYSA-N bitoscanate Chemical compound S=C=NC1=CC=C(N=C=S)C=C1 OMWQUXGVXQELIX-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical compound C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 230000035931 haemagglutination Effects 0.000 description 1
- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate group Chemical group [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
- ZBKFYXZXZJPWNQ-UHFFFAOYSA-N isothiocyanate group Chemical group [N-]=C=S ZBKFYXZXZJPWNQ-UHFFFAOYSA-N 0.000 description 1
- 239000003350 kerosene Substances 0.000 description 1
- 239000010699 lard oil Substances 0.000 description 1
- 235000021388 linseed oil Nutrition 0.000 description 1
- 239000000944 linseed oil Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- 150000003021 phthalic acid derivatives Chemical class 0.000 description 1
- 238000012643 polycondensation polymerization Methods 0.000 description 1
- 229920006389 polyphenyl polymer Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- BLTPNRTWCHWASU-UHFFFAOYSA-N propane-1,1,1-triamine Chemical compound CCC(N)(N)N BLTPNRTWCHWASU-UHFFFAOYSA-N 0.000 description 1
- ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical compound NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000012719 thermal polymerization Methods 0.000 description 1
- RUELTTOHQODFPA-UHFFFAOYSA-N toluene 2,6-diisocyanate Chemical compound CC1=C(N=C=O)C=CC=C1N=C=O RUELTTOHQODFPA-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
Landscapes
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Polyurethanes Or Polyureas (AREA)
Description
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The present invention relates to a method for producing microcapsules for immunoanalysis with high sensitization efficiency. BACKGROUND ART A hemagglutination reaction has traditionally been used as a method for immunologically testing antigens or antibodies. Furthermore, a latex aggregation reaction using polystyrene latex as a carrier has already been put into practical use. However, these conventional methods have drawbacks such as easy non-specific aggregation, insufficient sensitivity, poor long-term storage, and a long time required for determination. Instead of such red blood cells or latex,
A method using microcapsules as a carrier was proposed. (Unexamined Japanese Patent Publication No. 55-94636, No. 57-19661, No.
57â19662, etc.). This method eliminates the above-mentioned drawbacks inherent to animal-derived carriers (red blood cells) and the disadvantages of synthetic carriers such as latex.If this microcapsule carrier method is applied, sensitivity can be increased, simple operation, and - Improved effects compared to conventional methods, such as reliable determination of off state, are being obtained, and new tests that are practically impossible with conventional methods are being developed. The present inventors continued to conduct various studies on the performance of microcapsules as carriers for immunoassays, and found that microcapsules with a specific combination of core material, wall material, and additives could be used for highly sensitive immunoassays. It has been found that microcapsules can be obtained that provide reagents. That is, in the present invention, an oily substance liquid consisting of a polyvalent isocyanate and an oily substance is added to an aqueous solution containing polyvinyl alcohol and polystyrene sulfonic acid, emulsified and dispersed in the coexistence of polyvinyl alcohol and polystyrene sulfonic acid, and then a water-soluble polyvalent amino acid is added. The present invention relates to a method for producing microcapsules for immunoanalysis, which comprises adding a compound to the emulsified dispersion and polymerizing it with the polyvalent isocyanate. The microcapsules of the present invention are manufactured by the following steps. (1) An oily substance liquid is prepared by dissolving an oil-soluble polyvalent isocyanate, isothiocyanate, or a prepolymer thereof (hereinafter referred to as isocyanate) in an oily substance that forms the core. (2) Aqueous solution containing both PVA and PSS (PVA
-Prepare a PSS aqueous solution). (3) Adding an oily substance liquid to the PVA-PSS aqueous solution,
Emulsifying and dispersing in the coexistence of PVA and PSS. (4) Add a polyvalent amino compound to the emulsified dispersion. (5) Perform thermal polymerization (about 60 to 90â, usually about 70â)
(heat for at least 1 hour, usually about 2 hours). Microencapsulation is completed through the above steps. In the combination of a polyvalent isocyanate and a polyvalent amino compound, in which the condensation polymerization reaction progresses slowly, step (4) is
process, but this is not desirable. PVA and PSS must always coexist when emulsifying and dispersing polyvalent isocyanate. For example, even if one of them is emulsified and dispersed and the other is added afterwards to form a coexistence system, the microcapsules of the present invention cannot be obtained. The microcapsules thus obtained exhibit very high detection sensitivity in agglutination reactions when used as microcapsule reagents sensitized with antigens or antibodies. The microcapsules of the present invention can be produced only under the above combination conditions, and if any one of them is missing, the desired microcapsules will not be obtained.
The reason is not necessarily clear, but PVAâ
In the coexistence of PSS, polymerization at the interface is thought to be controlled extremely skillfully, and this seems to be due to the fact that the wall surface has many irregularities and therefore has a large surface area. PVA having a polymerization degree of about 200 to 1500 is usually used. If the degree of polymerization is too low, the emulsifying and dispersing power will be weak; if the degree of polymerization is too high, it will be difficult for antigens or antibodies to bind. It is desirable to use PVA in an amount of about 4 to 16% by weight based on the oily substance. There is no particular correlation with the degree of saponification as shown in microcapsules for pressure-sensitive paper (Japanese Patent Application Laid-Open No. 132631/1983), but in practical terms it is approximately 85%.
The above is good. A suitable PSS has a molecular weight of about 100,000 to 2 million, preferably 200,000 to 1 million, but practically 50
It is used with a degree of sulfonation ranging from 40 to 99%. The amount used is 10 to 100% by weight of PVA.
A range of is appropriate. The polyvalent amino compound used as a component of the wall material in the microcapsules of the present invention is a water-soluble primary amino compound. For example, linear diamines (ethylene, tetramethylene, hexamethylene, octamethylene diamine, etc.), diethylenetriamine, triethylenetetramine, tetraethylpentamine, aromatic diamines (phenylene, xylene diamine, diaminobenzoic acid, aminophenylethylamine) ), heterocyclic diamines (diamino-pyridine, -triazole, -pyrimidine, -mercaptopyrimidine, etc.), basic amino acids (arginine, lysine, hydroxylysine, ornithine, citrulline, glutamine, asparagine, etc.), triamines (triamino-propane, -benzene, -pyrimidine, etc.), among which linear diamines and basic amino acids, particularly hexamethylene diamine and lysine, are preferred. Oily substances that serve as capsule core materials include natural mineral oils, animal oils, vegetable oils, and synthetic oils. Since the surface of these core substances is completely covered by the capsule wall, they do not seem to have a direct effect on antigens or antibodies, but it is preferable to avoid biochemically active substances. Examples of mineral oils include kerosene, naphtha, and paraffin oil; examples of animal oils include fish oil and lard oil. Examples of vegetable oils include peanut oil, linseed oil, soybean oil, castor oil and corn oil. Examples of synthetic oils include biphenyl compounds (e.g., isopropylbiphenyl, isoamylbiphenyl), terphenyl compounds, naphthalene compounds (e.g., diisopropylnaphthalene), and alkylated diphenylalkanes (e.g., 2,4-dimethyldiphenylmethane). , phthalic acid compounds (eg, diethyl phthalate, dibutyl phthalate, dioctyl phthalate), chlorinated paraffin, and the like.
A polyvalent isocyanate, a polyvalent isothiocyanate, or a prepolymer thereof refers to a compound having two or more isocyanate groups or isothiocyanate groups and is soluble in an oily substance. Specific examples include m-phenylene diisocyanate, p-phenylene diisocyanate, 2,6-tolylene diisocyanate, 2,4-tolylene diisocyanate, naphthalene-1,4-diisocyanate, diphenylmethane. -4,4'-diisocyanate,
3,3'-dimethoxy-4,4'-biphenyl diisocyanate, 3,3'-dimethyldiphenylmethane-
4,4'-diisocyanate, xylylene-1,4
-diisocyanate, xylylene-1,3-diisocyanate, 4,4'-diphenylpropane diisocyanate, trimethylene diisocyanate,
Hexamethylene diisocyanate, propylene-
1,2-diisocyanate, butylene-1,2-
Diisocyanate, ethyridine diisocyanate, cyclohexylene-1,2-diisocyanate, cyclohexylene-1,4-diisocyanate, p-phenylene diisothiocyanate, xylylene-1,4-diisothiocyanate diisocyanate or diisothiocyanate such as diisothiocyanate, ethyridine diisothiocyanate; 4,4â²,4â³-triphenylmethane triisocyanate, toluene-2,
4,6-triisocyanate, polymethylene polyphenyl triisocyanate, 1,1,1-tris [(3-isocyanato-4-methylphenyl)
triisocyanates such as carbamoyloxymethyl]propane; tetraisocyanates such as 4,4'-dimethyldiphenylmethane-2,2',5,5'-tetraisocyanate; addition of hexamethylene diisocyanate and hexanetriol thing,
Adduct of 2,4-tolylene diisocyanate and Brenz catechol, adduct of tolylene diisocyanate and hexanetriol, adduct of tolylene diisocyanate and trimethylolpropane, adduct of xylylene diisocyanate and trimethylolpropane , a polyisocyanate prepolymer such as an adduct of hexamethylene diisocyanate and trimethylolpropane; or any similar suitable polyisocyanate or polyisothiocyanate. It is also possible to use two or more of these in combination. The amount used is oil-based liquid
It is preferably about 0.1 to 20 parts, particularly about 1 to 10 parts, per 100 parts. Other conditions for microencapsulation that can be applied to the method for producing microcapsules of the present invention are described in detail in "Microcapsules" by Asashi Kondo, published by Nikkan Kogyo Shimbun (1971), JP-A-72346-1973, etc. has been done. Although the specific gravity of the microcapsules of the present invention can be freely changed by changing the core material,
Generally speaking, a value within the range of 0.85-1.25 is appropriate for use as an immunological test. The average size of microcapsules is 0.5 ÎŒm ~
It is desirable to select from the range of 20 ÎŒm, preferably from 1 ÎŒm to 10 ÎŒm. Since the microcapsules of the present invention exhibit extremely high sensitization efficiency, they are extremely useful as carriers for immunoassay reagents. Furthermore, since it provides a highly sensitive immunological test reagent with a very high S/N ratio, it is extremely advantageous in terms of manufacturing costs. The present invention will be explained in more detail with reference to Examples below. Example 1 Oil-soluble red fluorescent dye oleosol Red BB was added to a mixed oil (specific gravity approximately 1.14) of 8.4 g of diisopropylnaphthalene and 16.6 g of chlorinated paraffin (Toyoparax 150, Toyo Soda Co., Ltd., chlorination degree 50%).
Oleosol Red BB (Sumitomo Chemical CI 26105) 0.25g
was dissolved. To the resulting solution was added 1,1,1-tris[(3-isocyanato-4-methylphenyl)carbamoyloxymethyl]propane (Burnock D
-750, manufactured by Dainippon Ink Co., Ltd.) dissolved in 2 g of methyl ethyl ketone was mixed. This oily substance liquid was mixed with 2 g of polyvinyl alcohol, PVA-105 (manufactured by Kuraray Co., Ltd., saponification degree 98%, polymerization degree 500) and a partial sodium salt of polystyrene sulfonic acid (manufactured by Procter-Gamble Co., Ltd., VERSA, TL-500,
(average molecular weight: 500,000) was added to a solution of 75 ml of water, and stirred and emulsified to prepare oil droplets with an average size of about 5 ÎŒm. Add a solution of 2.6 g of hexamethylene diamine dissolved in 25 ml of water, and
After diluting with 75 ml, the mixture was reacted at 70°C for 2 hours to perform microencapsulation. After the microcapsules were produced, they were centrifuged and washed with physiological saline to remove unreacted residues, and then dispersed in physiological saline so that the microcapsule particle concentration was 10%. Comparative microcapsule A: Polyvinyl alcohol, PVA-117 (manufactured by Kuraray Co., Ltd., instead of polyvinyl alcohol, PVA-105)
Microcapsules A were prepared under the same conditions as in Example 1, except that the degree of saponification was 98% and the degree of polymerization was 1700. Comparative Microcapsule B: Microcapsule B was prepared under the same conditions as in Example 1 except that 3 g of polyvinyl alcohol, PVA-105, was used without using polystyrene sulfonic acid. Comparative Microcapsule C: Microcapsule C was prepared under the same conditions as in Example 1 except that 2 g of polystyrene sulfonic acid was used without using polyvinyl alcohol or PVA-105. Using the above four types of microcapsules, microcapsule reagents were prepared by the following operations, and their sensitivities were compared. Preparation of microcapsule reagent and evaluation thereof Reagent A using microcapsules of the present invention 1.5 g of the microcapsules of the present invention prepared in Example 1 were taken out and diluted and dispersed in 8.5 ml of physiological saline. Next, 10 ml of a 25% glutaraldehyde aqueous solution diluted 100 times with physiological saline was added to the diluted microcapsule solution and reacted at 37°C for 45 minutes. After the reaction was completed, the mixture was washed by centrifugation and redispersed in 10 ml of physiological saline. Aliquot 2 ml of this, add 2 ml of Affinity chromatography-purified anti-human IgG antibody (sheep immune, manufactured by Wako Pure Chemical Industries, Ltd., 1% solution) diluted 200 times with physiological saline, and incubate at 37°C for 120 minutes. did. Then 0.15M containing 0.2% glycine
3 with phosphate buffered saline (PBS, PH=7.2)
After centrifugation and washing, it was dispersed in PBS containing 3% bovine serum albumin (BSA) to prepare a human IgG detection reagent. Comparative microcapsule reagents A, B, and C Comparative microcapsules A, B, and C were each treated with glutaraldehyde in the same manner as in the process, and Afinitei chromatographic purified anti-human
A subsequent reaction was performed using a 50-fold diluted solution of IgG antibody under the same conditions as in the step to obtain comparative reagents A, B, and C. Evaluation of reagents. An antigen-antibody reaction was performed using the microtiter method using the reagent A prepared in the following procedure. The tube in which obvious agglutination was observed was considered positive, and the highest dilution factor of the serum showing positive was determined.
This was taken as the antibody titer. 1% human IgG (Miles) 1% solution
Normal goat serum was diluted 20,000 times with PBS containing BSA, and normal goat serum was diluted 10 times with PBS containing 1% BSA as a negative control. Place 25Ό of each into each tube hole of the V-bottom microplate.
A dilution series was prepared by diluting the samples at 2-fold intervals using PBS containing 1% BSA. next. 25ÎŒ of the reagent A prepared in step A was collected with a dropper and dropped into the tube hole of the test solution dilution row of the microplate. The microplate was shaken for 5 minutes to advance the antigen-antibody reaction. After standing at room temperature for 3 hours, the aggregation image at the bottom of the microplate tube was observed, and the antibody titers as shown in Table 1 were obtained. ïŒïŒ Comparative microcapsule reagents A to C obtained in 1.
Antibody titers as shown in the table were obtained.
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åŸãã[Table] Reagent A, in which the microcapsules of the present invention are sensitized with anti-human IgG antibodies, is 800% lower than comparative reagent A.
It was found that the antibody titer was twice as high. In addition, the non-specific agglutination property measured by the negative control was lower than that of comparative reagents B and C, and a reagent with an extremely high signal-to-noise ratio was obtained. The reagent obtained using the microcapsules of the present invention provides a sufficiently high antibody titer at a lower antibody concentration than the comparative reagent, and is therefore extremely advantageous in terms of production cost. Anti-human that has not been purified by Affinity chromatography instead of anti-human IgG antibody purified by Affinity chromatography
The reaction was carried out under the same conditions as in the step except that IgG antibody (manufactured by Miles) was diluted 20 times with physiological saline to obtain anti-human IgG detection reagent B. According to the procedure, the antigen-antibody reaction was carried out using a microtiter method to determine the antibody titer, and the results shown in Table 2 were obtained.
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䟡ãæ±ãããåŸãããçµæã第ïŒè¡šã«ç€ºãã[Table] It has been found that the microcapsules of the present invention give sufficiently high antibody titers even when commercially available antibodies are directly immobilized thereon. Regarding the microcapsules of Comparative Examples A to C. Although the same conditions as above were performed, no agglutination images were observed in the human IgG dilution series. In the step, the diluted microcapsules were incubated at 37°C for 90 minutes using a 100-fold dilution of Affinitei chromatography-purified anti-human IgG antibody without being treated with glutaraldehyde to cause an adsorption reaction. Next, centrifugal washing with PBS was repeated three times, and human IgG was dispersed in PBS containing 3% BSA.
Detection reagent C was obtained. Following the inoculation, the antibody titer was determined by the microtiter method. The results obtained are shown in Table 3.
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䟡ãæ±ãããåŸãããçµæã第ïŒè¡šã«ç€ºãã[Table] Sufficiently high antibody titers were obtained even when antibodies were directly physically adsorbed onto the microcapsules of the present invention without using a crosslinking agent such as glutaraldehyde. Example 2 Microcapsules were prepared under the same conditions as in Example 1, except that 1.2 g of DL-lysine hydrochloride was dissolved in 25 ml of water instead of hexamethylene diamine, and the solution was neutralized with a caustic soda solution. 1.5 g of the microcapsules prepared in this example were taken out and diluted and dispersed in 8.5 ml of physiological saline. Then 1-ethyl-3-(3-dimethylaminopropyl)
Physiological saline containing 0.2% by weight of carbodiimide hydrochloride
10ml was added to the diluted microcapsules and reacted at 37°C for 45 minutes. After the reaction was completed, the mixture was washed by centrifugation and redispersed in 10 ml of physiological saline. Add the following to this 2ml. Sensitized microcapsules obtained by reacting Affinitei chromatographically purified anti-human IgG antibodies under
It was used as an IgG detection reagent. According to the procedure, the antibody titer was determined by the microtiter method. The results obtained are shown in Table 4.
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䟡ãæ±ãããåŸãããçµæã第ïŒè¡šã«ç€ºãã[Table] The reagent conjugated with antibodies to the microcapsules of the present invention using lysine as a component for forming the microcapsule wall gave extremely high antibody titers. Example 3 1.5 g of the microcapsules prepared in Example 1 were taken and diluted and dispersed in 8.5 ml of physiological saline.
10ml of physiological saline containing 1% by weight of n-propylamine
were mixed and incubated at 37°C for 45 minutes. After centrifugation and washing, the mixture was dispersed in 10 ml of physiological saline, and 10 ml of a 25% glutaraldehyde aqueous solution diluted 100 times with physiological saline was added thereto, followed by reaction at 37° C. for 45 minutes. After the reaction was completed, the mixture was washed by centrifugation and redispersed in 10 ml of physiological saline. Take 2 ml of this and react with Affinity chromatography purified anti-human IgG antibody in the same manner as in the step.
It was used as an IgG detection reagent. According to the procedure, the antibody titer was determined by the microtiter method. The results obtained are shown in Table 5.
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ãçµæã第ïŒè¡šã«ç€ºãã[Table] The reagent in which an amine compound was adsorbed to the microcapsules of the present invention and an antibody was bound using a crosslinking agent such as glutaraldehyde had a slightly stronger nonspecific aggregation property, but gave an extremely high antibody titer. In addition, linear amines (n-propylamine and n
-butylamine), diamines (hexamethylene diamine and octamethylene diamine) and basic amino acids (lysine, arginine, hydroxylysine). All of the obtained reagents gave extremely high antibody titers. Reference Example Leptospira autumnalis strain A was grown in Kortov's medium (containing 10% normal rabbit serum), and the culture solution after 6 to 10 days of culture was centrifuged at 9000 RPM for 20 minutes at 5°C. Dilute the sediment with physiological saline
After washing twice, it was redispersed in physiological saline and crushed for 10 minutes using a 20kHz sonicator (manufactured by Otake Seisakusho). This is centrifuged at 12,000 R.PM, and the precipitate is diluted with physiological saline to 10 times the original amount to prepare the antigen solution.
On the other hand, the supernatant was further centrifuged at 50,000 R.PM for 1 hour, and the supernatant was adjusted to have an optical density of 0.2 at a wavelength of 280 nm using a spectrophotometer, and used as an antigen solution. 1.5 g of the microcapsules prepared in Example 1 were separated and diluted and dispersed in 8.5 ml of physiological saline. To this dispersion, add 10 ml of a 25% glutaraldehyde aqueous solution diluted 100 times with physiological saline, and
It was allowed to react for a minute. Then, the mixture was washed by centrifugation and redispersed in 10 ml of physiological saline. Take 2 ml of this, add 2 ml each of the above antigen solutions A and B, and heat at 37â.
Incubated for 120 minutes. Next, perform centrifugation washing three times with PBS containing 0.2% glycine, then 3% BSA
By dispersing it in PBS containing Leptosvira autumnalis A disease detection reagents A and B were obtained. Rabbits were hyperimmunized with Leptospira autumnalis strain A to prepare antiserum. The Kortov medium culture of the autumn plague strain A was centrifuged, and the precipitated bacterial bodies were suspended in saline water. 4~
Rabbits were injected subcutaneously twice at 5-day intervals, followed by an additional 4-5
Nine intravenous injections are given at daily intervals. Seven to eight weeks had passed since the first subcutaneous injection, and after confirming that the mice had a predetermined antibody titer, whole blood was collected and antiserum was prepared. According to the procedure, the antibody titer was determined using a 100-fold dilution of the above antiserum using Leptospirosis A disease detection reagents (a) and (b) using the microtiter method. The results obtained are shown in Table 6.
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補ããããšãã§ããã[Table] Separate water-insoluble antigens and water-soluble antigens,
When the microcapsules of the present invention were sensitized to each antibody separately, reagents capable of detecting each antibody could be prepared.
Claims (1)
ã³é žãšãå«ã氎溶液ã«å€äŸ¡ã€ãœã·ã¢ããŒããšæ²¹æ§
ç©è³ªãããªãæ²¹æ§ç©è³ªæ¶²ãæ·»å ãããªããã«ã¢ã«
ã³ãŒã«ãšããªã¹ãã¬ã³ã¹ã«ãã³é žãšã®å ±åäžã«ä¹³
ååæ£ããã€ãã§æ°Žæº¶æ§å€äŸ¡ã¢ããååç©ãåèš
ä¹³ååæ£æ¶²ã«å ããŠåèšå€äŸ¡ã€ãœã·ã¢ããŒããšé
åãããããšãç¹åŸŽãšããå ç«åæçšãã€ã¯ãã«
ãã»ã«ã®è£œé æ³ã1 Add an oily substance liquid consisting of a polyvalent isocyanate and an oily substance to an aqueous solution containing polyvinyl alcohol and polystyrene sulfonic acid, emulsify and disperse in the coexistence of polyvinyl alcohol and polystyrene sulfonic acid, and then add the water-soluble polyvalent amino compound to the above-mentioned solution. A method for producing microcapsules for immunoanalysis, which comprises polymerizing the polyvalent isocyanate in addition to an emulsified dispersion.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP58147364A JPS6039562A (en) | 1983-08-12 | 1983-08-12 | Microcapsule for immunoreaction and its production |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP58147364A JPS6039562A (en) | 1983-08-12 | 1983-08-12 | Microcapsule for immunoreaction and its production |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS6039562A JPS6039562A (en) | 1985-03-01 |
JPH0510626B2 true JPH0510626B2 (en) | 1993-02-10 |
Family
ID=15428534
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP58147364A Granted JPS6039562A (en) | 1983-08-12 | 1983-08-12 | Microcapsule for immunoreaction and its production |
Country Status (1)
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JP (1) | JPS6039562A (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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JPH059809Y2 (en) * | 1987-08-21 | 1993-03-10 |
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1983
- 1983-08-12 JP JP58147364A patent/JPS6039562A/en active Granted
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JPS6039562A (en) | 1985-03-01 |
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