CN105949343B - A kind of preparation method of the synthetic method of aldehydedodextrans, the method for coating based on the aldehydedodextrans and microsphere composition - Google Patents
A kind of preparation method of the synthetic method of aldehydedodextrans, the method for coating based on the aldehydedodextrans and microsphere composition Download PDFInfo
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- CN105949343B CN105949343B CN201610289196.XA CN201610289196A CN105949343B CN 105949343 B CN105949343 B CN 105949343B CN 201610289196 A CN201610289196 A CN 201610289196A CN 105949343 B CN105949343 B CN 105949343B
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- microballoon
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- 238000000034 method Methods 0.000 title claims abstract description 50
- 239000004005 microsphere Substances 0.000 title claims abstract description 39
- 239000000203 mixture Substances 0.000 title claims abstract description 33
- 238000000576 coating method Methods 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- 238000010189 synthetic method Methods 0.000 title claims abstract description 30
- 239000011248 coating agent Substances 0.000 title claims abstract description 29
- 238000006243 chemical reaction Methods 0.000 claims abstract description 45
- -1 halo acetal Chemical class 0.000 claims abstract description 34
- 238000007037 hydroformylation reaction Methods 0.000 claims abstract description 19
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229920001503 Glucan Polymers 0.000 claims abstract description 17
- 239000004593 Epoxy Substances 0.000 claims abstract description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 8
- 230000007062 hydrolysis Effects 0.000 claims abstract description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 132
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 102
- 239000001301 oxygen Substances 0.000 claims description 102
- 229910052760 oxygen Inorganic materials 0.000 claims description 102
- 239000000243 solution Substances 0.000 claims description 84
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 54
- 239000008363 phosphate buffer Substances 0.000 claims description 48
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 38
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 claims description 35
- 239000007787 solid Substances 0.000 claims description 35
- 238000004176 ammonification Methods 0.000 claims description 34
- 238000001556 precipitation Methods 0.000 claims description 31
- 238000004140 cleaning Methods 0.000 claims description 30
- 150000003384 small molecules Chemical class 0.000 claims description 26
- 235000019441 ethanol Nutrition 0.000 claims description 24
- 229910052693 Europium Inorganic materials 0.000 claims description 22
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 claims description 22
- 238000003756 stirring Methods 0.000 claims description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- 238000010992 reflux Methods 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 239000012074 organic phase Substances 0.000 claims description 18
- 230000001235 sensitizing effect Effects 0.000 claims description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 16
- 238000000502 dialysis Methods 0.000 claims description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 15
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 14
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 14
- 239000007864 aqueous solution Substances 0.000 claims description 14
- 229910052796 boron Inorganic materials 0.000 claims description 14
- 238000001953 recrystallisation Methods 0.000 claims description 14
- DHDHJYNTEFLIHY-UHFFFAOYSA-N 4,7-diphenyl-1,10-phenanthroline Chemical compound C1=CC=CC=C1C1=CC=NC2=C1C=CC1=C(C=3C=CC=CC=3)C=CN=C21 DHDHJYNTEFLIHY-UHFFFAOYSA-N 0.000 claims description 13
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 claims description 13
- 239000013078 crystal Substances 0.000 claims description 13
- 239000012510 hollow fiber Substances 0.000 claims description 13
- 239000002243 precursor Substances 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 238000013329 compounding Methods 0.000 claims description 12
- 229910052761 rare earth metal Inorganic materials 0.000 claims description 12
- 150000002910 rare earth metals Chemical class 0.000 claims description 12
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 11
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 11
- 239000007788 liquid Substances 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 9
- STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 9
- OIAQMFOKAXHPNH-UHFFFAOYSA-N 1,2-diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1C1=CC=CC=C1 OIAQMFOKAXHPNH-UHFFFAOYSA-N 0.000 claims description 8
- KOFZTCSTGIWCQG-UHFFFAOYSA-N 1-bromotetradecane Chemical compound CCCCCCCCCCCCCCBr KOFZTCSTGIWCQG-UHFFFAOYSA-N 0.000 claims description 8
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 claims description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 7
- JKXCZYCVHPKTPK-UHFFFAOYSA-N hydrate;trihydrochloride Chemical compound O.Cl.Cl.Cl JKXCZYCVHPKTPK-UHFFFAOYSA-N 0.000 claims description 7
- 239000011734 sodium Substances 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 239000011630 iodine Substances 0.000 claims description 6
- ILCQYORZHHFLNL-UHFFFAOYSA-N n-bromoaniline Chemical compound BrNC1=CC=CC=C1 ILCQYORZHHFLNL-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 239000011592 zinc chloride Substances 0.000 claims description 6
- 235000005074 zinc chloride Nutrition 0.000 claims description 6
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 5
- 239000008346 aqueous phase Substances 0.000 claims description 5
- 239000012535 impurity Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 5
- 239000010452 phosphate Substances 0.000 claims description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 5
- 239000012279 sodium borohydride Substances 0.000 claims description 5
- 238000000967 suction filtration Methods 0.000 claims description 5
- 229910052771 Terbium Inorganic materials 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 229930002868 chlorophyll a Natural products 0.000 claims description 4
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 229960004337 hydroquinone Drugs 0.000 claims description 4
- 238000003786 synthesis reaction Methods 0.000 claims description 4
- GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 claims description 4
- 230000008859 change Effects 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 claims description 3
- 229960000907 methylthioninium chloride Drugs 0.000 claims description 3
- XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 claims description 3
- 239000011261 inert gas Substances 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 3
- 150000005208 1,4-dihydroxybenzenes Chemical class 0.000 claims 1
- POEOLRMDMUNLPY-UHFFFAOYSA-N 2,3-diphenyl-1,10-phenanthroline Chemical compound C1=CC=CC=C1C1=CC2=CC=C(C=CC=N3)C3=C2N=C1C1=CC=CC=C1 POEOLRMDMUNLPY-UHFFFAOYSA-N 0.000 claims 1
- QRLRDGCQATZBAK-UHFFFAOYSA-N [B].N#CC#N Chemical compound [B].N#CC#N QRLRDGCQATZBAK-UHFFFAOYSA-N 0.000 claims 1
- WRLRISOTNFYPMU-UHFFFAOYSA-N [S].CC1=CC=CC=C1 Chemical compound [S].CC1=CC=CC=C1 WRLRISOTNFYPMU-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 239000007853 buffer solution Substances 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 8
- 238000004132 cross linking Methods 0.000 abstract description 5
- 239000000463 material Substances 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 5
- 230000009286 beneficial effect Effects 0.000 abstract description 4
- 238000005576 amination reaction Methods 0.000 abstract description 3
- 230000002349 favourable effect Effects 0.000 abstract description 3
- 230000000977 initiatory effect Effects 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 230000008878 coupling Effects 0.000 abstract description 2
- 238000010168 coupling process Methods 0.000 abstract description 2
- 238000005859 coupling reaction Methods 0.000 abstract description 2
- 150000002431 hydrogen Chemical class 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 8
- 239000000843 powder Substances 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- BZYUMXXOAYSFOW-UHFFFAOYSA-N 2,3-dimethylthiophene Chemical compound CC=1C=CSC=1C BZYUMXXOAYSFOW-UHFFFAOYSA-N 0.000 description 5
- 238000007539 photo-oxidation reaction Methods 0.000 description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- GHKCSRZBNZQHKW-UHFFFAOYSA-N 1-sulfanylethanol Chemical class CC(O)S GHKCSRZBNZQHKW-UHFFFAOYSA-N 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 239000005864 Sulphur Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 125000005909 ethyl alcohol group Chemical group 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 150000002978 peroxides Chemical class 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 238000001994 activation Methods 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000005661 hydrophobic surface Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- SJOLAWBAJBCHLW-UHFFFAOYSA-N 1-bromo-1,1-diethoxyethane Chemical compound CCOC(C)(Br)OCC SJOLAWBAJBCHLW-UHFFFAOYSA-N 0.000 description 1
- XQQBUAPQHNYYRS-UHFFFAOYSA-N 2-methylthiophene Chemical compound CC1=CC=CS1 XQQBUAPQHNYYRS-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- QENGPZGAWFQWCZ-UHFFFAOYSA-N Methylthiophene Natural products CC=1C=CSC=1 QENGPZGAWFQWCZ-UHFFFAOYSA-N 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- IPTOYISYIDUYAC-UHFFFAOYSA-N [C-]#N.[Na+].[B+3].[C-]#N.[C-]#N.[C-]#N Chemical compound [C-]#N.[Na+].[B+3].[C-]#N.[C-]#N.[C-]#N IPTOYISYIDUYAC-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004308 accommodation Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- SISAYUDTHCIGLM-UHFFFAOYSA-N bromine dioxide Inorganic materials O=Br=O SISAYUDTHCIGLM-UHFFFAOYSA-N 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 description 1
- 229960004419 dimethyl fumarate Drugs 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/12—Chemical modification
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2325/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring; Derivatives of such polymers
- C08J2325/02—Homopolymers or copolymers of hydrocarbons
- C08J2325/04—Homopolymers or copolymers of styrene
- C08J2325/06—Polystyrene
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to the preparation method of a kind of synthetic method of aldehydedodextrans, the method for coating based on the aldehydedodextrans and microsphere composition.The hydroformylation glucan is using halo acetal and glucan as raw material, is substituted, hydrolysis forms, and the aldehyde radical of generation is not susceptible to cross-linking reaction, and active group aldehyde radical density is controllable, favorable reproducibility, is more beneficial for the connection of monoclonal antibody, albumen.The method for coating is using epoxy ethyl particulate as initiation material, instead of traditional carboxyl particulate.Amination can be replaced sugared with organic molecule, whole coating process seems that simple, cycle is short, preferably to be used for industrialized production.The preparation method of the microsphere composition, the hydroformylation glucan is coated on microsphere surface and forms covalent coupling of the aldehydedodextrans microballoon for biomolecule, this method technique is simple, easy to operate, reproducible.
Description
Technical field
The invention belongs to the field of chemical synthesis, and in particular to a kind of synthetic method of aldehydedodextrans, based on the aldehyde radical
The method for coating of glucan and the preparation method of microsphere composition.
Background technology
Polystyrene microsphere has been widely used in medical diagnostic field, and its cardinal principle is that protein can be by a variety of sides
Formula is covalently bonded to microsphere surface.Microsphere surface can modify the group of the functionalization such as epoxy radicals, chloromethyl, aldehyde radical, carboxyl, all
It can be reacted with the amino at the Fc ends of antibody, form covalent bond.When covalent cross-linking mode is selected, generally require to examine
Consider effect phase, complex process degree and the last charge stable situation of crosslinking.First three group can directly with albumen amino
Reaction, covalent bond is formed, use more convenient, but storage stability is slightly worse than carboxyl microballoon.And carboxyl microballoon then need through
Cross after EDC/NHS activation, just the amino with albumen reacts, and forms covalent bond, this method is relatively stable, and is current
The labeling method of in the market main flow.
But there is also defect for this method：
1, using carboxyl particulate as raw material, activate to form amino particulate by adding EDC/NHS, then with the amino in albumen
Reacted.The reaction compared to the reaction of aldehyde radical one-step method is more easy to that particulate occurs because adding essential activation process
Union phenomenon, condition are difficult to control.
2, because microsphere surface is in addition to carboxyl, remaining is all the hydrophobic surface of naked leakage, and these hydrophobic surfaces are in egg
In vain with nonspecific absorption easily occurs in the cohesive process of microballoon, and it is easier by solvent, pH even salinity
Influence, so as to interference detection results.
The content of the invention
In order to solve above mentioned problem existing for prior art, the invention provides a kind of synthetic method of aldehydedodextrans,
The preparation method of method for coating and microsphere composition based on the aldehydedodextrans.The present invention proposes a kind of brand-new aldehyde radical
The synthetic method of glucan, and be coated on microsphere surface and form the covalent idol that aldehydedodextrans microballoon is used for biomolecule
Connection, this method technique are simple, easy to operate, reproducible.
The technical solution adopted in the present invention is：
A kind of synthetic method of aldehydedodextrans,
The novel synthesis circuit of aldehydedodextrans can represent as follows：
Comprise the following steps：
A, after glucan being dissolved in into water, under inert gas shielding, EDTA, 1, 4-benzenediol, sodium borohydride, NaOH are added
And toluene, it is stirred at reflux 1-3 hours；
B, bromo- 1, the 1- diethoxyethane solution of 2- is added dropwise into system, time for adding is no less than 1 hour；It is added dropwise to complete
Afterwards, 12-18 hours are stirred at reflux；
C, the organic phase in system is washed with water, obtains the aqueous solution, the aqueous solution is added in methanol, obtains hydroformylation sugar
Precursor precipitation；
D, it is hydroformylation sugar precursor precipitation is soluble in water, add toluenesulfonic acid and adjust pH to 1-2, after heating hydrolysis, use
NaOH solution is adjusted to neutrality, and aldehydedodextrans are obtained in the form of precipitation.
By above-mentioned steps, it can synthesize that purity is good, the aldehydedodextrans of high income.
Preferably, a kind of synthetic method of aldehydedodextrans, comprises the following steps：
A, after the glucan of 20000-40000 parts by weight being dissolved in the water of 50-130 parts by volume, under nitrogen protection, add
The 1, 4-benzenediol of EDTA, 5-15 parts by weight of 5-15 parts by weight, the sodium borohydride of 5-15 parts by weight, 4000-8000 parts by weight
NaOH and 40-80 parts by volume toluene, be stirred at reflux 1-3 hours；
B, the toluene solution of bromo- 1, the 1- diethoxyethane of 2- is added dropwise into system, time for adding is no less than 1 hour, 2-
The volume ratio of bromo- 1,1- diethoxyethane and toluene is 1:4-5；After being added dropwise to complete, 12-18 hours are stirred at reflux；
C, after being cooled to room temperature, the organic phase in system is washed with water three times, the volume of water used is 120-180 every time
Parts by volume, merge aqueous phase and obtain the aqueous solution, the aqueous solution is added in the methanol of 1500-2500 parts by volume, and ethanol is used after suction filtration
Three times, the volume of ethanol used is 200-280 parts by volume every time for washing, and washed precipitation is dried in vacuo, and obtains hydroformylation
Sugar precursor precipitates；
D, the hydroformylation sugar precursor precipitation of 5000-15000 parts by weight is dissolved in the water of 30-70 parts by volume, adds first
Benzene sulfonic acid adjusts pH to 1-2, is heated to 70-90 DEG C and is hydrolyzed, and after hydrolyzing 1-3 hours, use quality fraction is 30-50%'s
NaOH solution is adjusted to neutrality, and after filtering, removal of impurities, aldehydedodextrans are obtained in the form of precipitation.
Present invention also offers a kind of method for coating based on the aldehydedodextrans synthetic method,
The coating circuit signal of aldehydedodextrans can represent as follows, and wherein microballoon is represented with ball：
Comprise the following steps：
A, microballoon is added in 1,6- hexamethylene diamine solution, reacts 8-16 hours, obtain ammonification microballoon；
B, the aldehydedodextrans are dissolved in phosphate buffer, add the ammonification microballoon, dripped after well mixed
Add three hydrogen boron sodium cyanide solutions, react 8-16 hours；
C, eccentric cleaning, obtain being coated with the microballoon of aldehydedodextrans.
Preferably, a kind of method for coating based on the aldehydedodextrans synthetic method, comprises the following steps：
A, at 70 DEG C, the mass fraction that the epoxy ethyl microballoon of 500-1500 parts by weight is added to 10-30 parts by volume is
In 10% 1,6- hexamethylene diamine solution, at 90 DEG C after stirring reaction 8-16 hours, removed not through dialysis or hollow fiber conduit cleaning
The small molecule of reaction, obtain ammonification microballoon；
B, the aldehydedodextrans of 2000-3000 parts by weight are dissolved in the phosphate buffer of 40-60 parts by volume,
The concentration of the phosphate buffer is 0.1mol/L, the pH=6.0 of the phosphate buffer, adds the ammonification microballoon,
Three hydrogen boron sodium cyanide solutions are added dropwise after well mixed, the three hydrogen boron sodium cyanide solution is three hydrogen boron Cymags of 400 parts by weight
It is dissolved in the 0.1mol/L phosphate buffers of 2.5 parts by volume and obtains, 8-16 hours is reacted at 37 DEG C；
C, eccentric cleaning removes unreacted small molecule, obtains being coated with the microballoon of aldehydedodextrans.
The synthetic method and method for coating of the aldehydedodextrans have following advantages：
1st, the hydroformylation glucan is using halo acetal and glucan as raw material, is substituted, hydrolysis forms, generation
Aldehyde radical is not susceptible to cross-linking reaction, and active group aldehyde radical density is controllable, favorable reproducibility, is more beneficial for the connection of monoclonal antibody, albumen.
2nd, the method for coating is using epoxy ethyl particulate as initiation material, instead of traditional carboxyl particulate.Can be with organic
Small molecule replaces amination sugar, and whole coating process seems that simple, cycle is short, preferably to be used for industrialized production.
Present invention also offers a kind of preparation method of the microsphere composition based on the method for coating, including following step
Suddenly：
A, prepared by oxygen microballoon：Thioxene, β-two butanone and rare earth compounding are put into microballoon, formed by oxygen
Microballoon；
B, the preparation of microballoon is supplied oxygen：Sensitising agent is put into microballoon, forms oxygen supply microballoon；
C, aldehydedodextrans coating microballoon：It will be added by oxygen microballoon or oxygen supply microballoon in 1,6- hexamethylene diamine solution, and react 8-
16 hours, obtain ammonification microballoon；The aldehydedodextrans are dissolved in phosphate buffer, add the ammonification microballoon, are mixed
Three hydrogen boron sodium cyanide solutions are added dropwise after closing uniformly, react 8-16 hours；Eccentric cleaning, obtain being coated with aldehydedodextrans by oxygen
Microballoon or oxygen supply microballoon；
D, it is described to be combined as microsphere composition by oxygen microballoon and oxygen supply microballoon.
Preferably, a kind of preparation method of microsphere composition, comprises the following steps：
A, prepared by oxygen microballoon：Thioxene, β-two butanone and rare earth compounding are put into microballoon, formed by oxygen
Microballoon；
B, the preparation of microballoon is supplied oxygen：Sensitising agent is put into microballoon, forms oxygen supply microballoon；
C, aldehydedodextrans coating microballoon：At 70 DEG C, 500-1500 parts by weight are added by oxygen microballoon or oxygen supply microballoon
The mass fraction of 10-30 parts by volume is in 10% 1,6- hexamethylene diamine solution, at 90 DEG C after stirring reaction 8-16 hours, through dialysis
Or hollow fiber conduit cleaning removes unreacted small molecule, obtains ammonification microballoon；By the aldehyde radical Portugal of 2000-3000 parts by weight
Glycan is dissolved in the phosphate buffer of 40-60 parts by volume, and the concentration of the phosphate buffer is 0.1mol/L, the phosphorus
The pH=6.0 of phthalate buffer, the ammonification microballoon is added, three hydrogen boron sodium cyanide solutions, three hydrogen is added dropwise after well mixed
Boron sodium cyanide solution is dissolved in the 0.1mol/L phosphate buffers of 2.5 parts by volume for three hydrogen boron Cymags of 400 parts by weight to be obtained
Arrive, 8-16 hours are reacted at 37 DEG C；Eccentric cleaning removes unreacted small molecule, obtains being coated with the micro- by oxygen of aldehydedodextrans
Ball or oxygen supply microballoon；
D, it is described to be combined as microsphere composition by oxygen microballoon and oxygen supply microballoon.
Preferably, the rare earth compounding is europium complex or terbium coordination compound；The sensitising agent is that photooxidation dye substance is sub-
Methyl blue, rose-red, one kind or combination in phthalocyanine compound and chlorophyll A.Because the europium complex and terbium coordination compound
Property is close, can meet the needs of the present invention.
Preferably, the synthetic method of the europium complex, comprises the following steps：
A, adjacent phenyl biphenyl is dissolved in dichloromethane, is added aluminium chloride, is cooled to 0 DEG C；Chloroacetic chloride is added dropwise, is added dropwise
1-2 hours are reacted at room temperature afterwards, are dried to obtain solids I；
B, the solids I is dissolved in absolute ether, adds sodium methoxide and Trifluoroacetic Acid Ethyl Ester, react at room temperature 2-3
Hour, it is dried to obtain solids II；
C, six trichloride hydrate europiums are well mixed with the solids II, add absolute ethyl alcohol dissolving, stirring adds ammonia
After reacting at room temperature 1-2 hours, water is added into system to pH to 7-9 for water, is filtered, is dried to obtain solids III；
D, take 4,7- diphenyl -1,10- phenanthroline to dissolve by heating and recrystallization crystal is collected after ethanol, cooling；Take described
Recrystallize crystal and 4,7- diphenyl -1,10- phenanthroline are added in toluene, stir 1-2 hours, be cooled to room temperature, except toluene, obtain
To europium complex.
Further, the synthetic method of the europium complex, comprises the following steps
A, the adjacent phenyl biphenyl of 4500-5000 parts by weight is dissolved in the anhydrous methylene chloride of 30-50 parts by volume, added
The aluminium chloride of 5500-6000 parts by weight, it is cooled to 0 DEG C；The chloroacetic chloride of 3500-4500 parts by weight is added dropwise, rear room temperature is added dropwise
1-2 hours are reacted, after the organic phase in system is washed with water three times, 5000-6000 weight is obtained with anhydrous sodium sulfate drying
Part solids I；
B, take the solids I of 3000-3500 parts by weight to be dissolved in the absolute ether of 30-50 parts by volume, add
The sodium methoxide of 1500-2500 parts by weight and the Trifluoroacetic Acid Ethyl Ester of 3000-5000 parts by weight, 2-3 hours are reacted at room temperature, by system
In organic phase be washed with water three times after, obtain the solids II of 1000-2000 parts by weight with anhydrous sodium sulfate drying；
C, six trichloride hydrate europiums of 2800-3200 parts by weight and the solids II of 6000-6800 parts by weight are mixed
The absolute ethyl alcohol dissolving for uniformly adding 30-50 parts by volume is closed, stirring adds the ammoniacal liquor of 1500-2500 parts by volume to pH to 7-9,
After room temperature reaction 1 hour, the water of 600-1000 parts by volume is added into system, precipitation is collected by filtration, and precipitation is dried to obtain
Solids III；
D, 4,7- diphenyl -1,10- phenanthroline of 3000-5000 parts by weight is taken to dissolve by heating in 100-150 parts by volume
Ethanol, recrystallization crystal is collected after cooling；Take the recrystallization crystal and 800-1200 parts by weight of 2500-3500 parts by weight
4,7- diphenyl -1,10- phenanthroline are added in the toluene of 200-400 parts by volume, and 1-2 hours are stirred at 62 DEG C, are cooled to room temperature,
Except toluene, europium complex is obtained.
Preferably, the synthetic method of thioxene and β-two butanone, comprises the following steps：
A, bromoaniline is dissolved in DMF, adds bromotetradecane and diisopropylethylamine, 100 DEG C of reaction 10-14 are small
Shi Hou, dichloromethane is added into reaction solution, recrystallize to obtain N, the dibasic para-bromoaniline of N-；
B, the N, the dibasic para-bromoaniline of N-, magnesium rod and iodine are dissolved in wiring solution-forming in THF, maintain the reflux for condition
Under, solution is added drop-wise in THF, back flow reaction 1 hour after liquid feeding, 0 DEG C is cooled to, benzoyl hydroperoxide is added into system
And THF, 2-3 hours are reacted at room temperature；After hydrochloric acid is added into system to hydrolyze the salt of generation, dichloromethane is added into system
Alkane, dry and chromatograph isolated intermediate；
C, the intermediate is dissolved in toluene solution, adds zinc chloride and 2 mercapto ethanol, back flow reaction 3-5 are small
When, except toluene chromatographs to obtain thioxene and β-two butanone.
Further, the synthetic method of thioxene and β-two butanone, comprises the following steps：
A, the bromoaniline of 30000-40000 parts by weight is dissolved in the DMF of 100-150 parts by volume, adds 120000-
The bromotetradecane of 200000 parts by weight and the diisopropylethylamine of 50000-100000 parts by weight, after 100 DEG C are reacted 12 hours,
The dichloromethane of 200-400 parts by volume is added into reaction solution, after system is washed with water three times, ethyl alcohol recrystallization is added, obtains
The dibasic para-bromoaniline of N, N-；
B, the N, the dibasic para-bromoaniline of N-, the magnesium rod of 2500-3500 parts by weight and iodine are dissolved in 40-60 volumes
Wiring solution-forming in the THF of part, and solution is added drop-wise in the THF of 80-120 parts by volume and maintained the reflux for, flowed back after liquid feeding anti-
It should react 1 hour, be cooled to 0 DEG C, the benzoyl hydroperoxide and 40-60 parts by volume of 10000-15000 parts by weight are added into system
THF, at room temperature react 2-3 hours；Into system add molar concentration be 0.1mol/L hydrochloric acid to hydrolyze the salt of generation after, to
The dichloromethane of 150-250 parts by volume is added in system, after the organic phase in system is washed with water three times, uses anhydrous sodium sulfate
Dry, column chromatography for separation obtains intermediate；
C, the intermediate is dissolved in the toluene solution of 80-120 parts by volume, adds zinc chloride and 7000-10000 weights
The 2 mercapto ethanol of part is measured, back flow reaction 3-5 hours, except toluene, column chromatography obtains thioxene and β-two butanone.
On the english abbreviation and the Name Resolution of other materials occurred in the present invention：
DMF：Dimethyl fumarate, No. CAS：68-12-2；
THF；Tetrahydrofuran, No. CAS：109-99-9；
DPP：4,7- diphenyl -1,10- phenanthroline, No. CAS：1662-01-7；
EDTA：Ethylenediamine tetra-acetic acid, No. CAS：60-00-4；
1, 4-benzenediol, No. CAS：123-31-9；
Sodium borohydride, No. CAS：16940-66-2；
Bromo- 1, the 1- diethoxyethane of 2-, chemical formula：C6H13BrO2, No. CAS：2032-35-1；
Toluenesulfonic acid, No. CAS：98-11-3；
1,6- hexamethylene diamine, No. CAS：124-09-4；
Three hydrogen boron Cymags, also known as sodium cyanoborohydride, No. CAS：25895-60-7；
2,5 thioxenes, No. CAS：638-02-8；
Adjacent phenyl biphenyl, C12H10, No. CAS：92-52-4；
Chloroacetic chloride, No. CAS：75-36-5；
Trifluoroacetic Acid Ethyl Ester；No. CAS：383-63-1；
To amino bromination benzene, No. CAS：106-40-1；
Bromotetradecane, No. CAS：112-71-0；
Diisopropylethylamine, No. CAS：7087-68-5；
In the present invention, water used is deionized water.
It should be noted that parts by weight and parts by volume in the present invention, it is intended merely to show the proportionate relationship of each material, and
Some quantitative value is not represented specifically, and in the present invention, the parts by weight and parts by volume have following corresponding relation：When 1 parts by weight are
During 1g, 1 parts by volume is 1L.
Beneficial effects of the present invention are：
1st, the hydroformylation glucan is using halo acetal and glucan as raw material, is substituted, hydrolysis forms, generation
Aldehyde radical is not susceptible to cross-linking reaction, and active group aldehyde radical density is controllable, favorable reproducibility, is more beneficial for the connection of monoclonal antibody, albumen.
2nd, the method for coating is using epoxy ethyl particulate as initiation material, instead of traditional carboxyl particulate.Can be with organic
Small molecule replaces amination sugar, and whole coating process seems that simple, cycle is short, preferably to be used for industrialized production.
3rd, the preparation method of the microsphere composition, the hydroformylation glucan is coated on microsphere surface formation aldehyde radical Portugal and gathered
Sugared microballoon is used for the covalent coupling of biomolecule, and this method technique is simple, easy to operate, reproducible.
Embodiment
In the present invention, if not refering in particular to, all parts, percentage are unit of weight, and all equipment and raw material etc. are equal
It is commercially available or the industry is conventional.Method in following embodiments, it is the routine of this area unless otherwise instructed
Method.
The invention provides a kind of synthetic method of aldehydedodextrans, the method for coating based on the aldehydedodextrans
With the preparation method of microsphere composition.
With reference to embodiment, present disclosure is further illustrated.It should be appreciated that the implementation of the present invention is not limited to
In the following examples, any formal accommodation and/or change made to the present invention fall within the scope of the present invention.
Embodiment 1
A kind of synthetic method of aldehydedodextrans, comprises the following steps：
A, after 30g glucans being dissolved in into 90ml water, under nitrogen protection, 10mg EDTA, 10mg1,4- benzene two are added
Phenol, 10mg sodium borohydrides, 6g NaOH and 60ml toluene, are stirred at reflux 2 hours；
B, the toluene solution of bromo- 1, the 1- diethoxyethane of 2- is slowly added dropwise into system, time for adding is small no less than 1
When, the toluene solution of bromo- 1, the 1- diethoxyethane of 2- is dissolved in 200ml toluene for bromo- 1, the 1- diethoxyethane of 50ml2-
It is made in solution；After being added dropwise to complete, it is stirred at reflux 15 hours；
C, after being cooled to room temperature, the organic phase in system is washed with water three times, the volume of water used is 150ml every time,
Merge aqueous phase and obtain the aqueous solution, the aqueous solution is added in 2000ml methanol, washed three times with ethanol after suction filtration, used every time
The volume of ethanol is 240ml, and washed precipitation is dried in vacuo, and obtains 33g hydroformylations sugar precursor precipitation；
D, hydroformylation sugar precursor precipitation described in 10g is dissolved in 50ml water, adds toluenesulfonic acid and adjust pH to 1-2, be heated to 80
DEG C it is hydrolyzed, after hydrolysis 2 hours, the NaOH solution that use quality fraction is 40% is adjusted to neutrality, and filtering, dialysis or centrifugation are clear
Small molecular weight impurity is removed in washout, freezes to obtain aldehydedodextrans freeze-dried powder 9g.
Embodiment 2
A kind of synthetic method of aldehydedodextrans, comprises the following steps：
A, after 20g glucans being dissolved in into 130ml water, under nitrogen protection, 5mg EDTA, 15mg1,4- benzene two are added
Phenol, 5mg sodium borohydrides, 8g NaOH and 40ml toluene, are stirred at reflux 3 hours；
B, the toluene solution of bromo- 1, the 1- diethoxyethane of 2- is slowly added dropwise into system, time for adding is small no less than 1
When, the toluene solution of bromo- 1, the 1- diethoxyethane of 2- is dissolved in 200ml toluene for bromo- 1, the 1- diethoxyethane of 40ml2-
It is made in solution；After being added dropwise to complete, it is stirred at reflux 12 hours；
C, after being cooled to room temperature, the organic phase in system is washed with water three times, the volume of water used is 180ml every time,
Merge aqueous phase and obtain the aqueous solution, the aqueous solution is added in 1500ml methanol, washed three times with ethanol after suction filtration, each institute
It is 280ml with the volume of ethanol, and washed precipitation is dried in vacuo, obtains 22g hydroformylations sugar precursor precipitation；
D, hydroformylation sugar precursor precipitation described in 5g is dissolved in 70ml water, adds toluenesulfonic acid and adjust pH to 1-2, be heated to 70 DEG C
It is hydrolyzed, after hydrolyzing 3 hours, the NaOH solution that use quality fraction is 30% is adjusted to neutrality, filtering, dialysis or eccentric cleaning
Small molecular weight impurity is removed, freezes to obtain aldehydedodextrans freeze-dried powder 4.5g.
Embodiment 3
A kind of synthetic method of aldehydedodextrans, comprises the following steps：
A, after 40g glucans being dissolved in into 50ml water, under nitrogen protection, addition 15mg EDTA, 5mg1,4- benzenediols,
15mg sodium borohydrides, 4g NaOH and 80ml toluene, are stirred at reflux 1 hour；
B, the toluene solution of bromo- 1, the 1- diethoxyethane of 2- is slowly added dropwise into system, time for adding is small no less than 1
When, the toluene solution of bromo- 1, the 1- diethoxyethane of 2- is dissolved in 200ml toluene for bromo- 1, the 1- diethoxyethane of 45ml2-
It is made in solution；After being added dropwise to complete, it is stirred at reflux 18 hours；
C, after being cooled to room temperature, the organic phase in system is washed with water three times, the volume of water used is 120ml every time,
Merge aqueous phase and obtain the aqueous solution, the aqueous solution is added in 2500ml methanol, washed three times with ethanol after suction filtration, used every time
The volume of ethanol is 200ml, and washed precipitation is dried in vacuo, and obtains 44g hydroformylations sugar precursor precipitation；
D, hydroformylation sugar precursor precipitation described in 15g is dissolved in 30ml water, adds toluenesulfonic acid and adjust pH to 1-2, be heated to 90
DEG C it is hydrolyzed, after hydrolysis 1 hour, the NaOH solution that use quality fraction is 50% is adjusted to neutrality, and filtering, dialysis or centrifugation are clear
Small molecular weight impurity is removed in washout, freezes to obtain aldehydedodextrans freeze-dried powder 13.5g.
Embodiment 4
A kind of method for coating based on aldehydedodextrans described in embodiment 1, comprises the following steps：
A, at 70 DEG C, 1g epoxy ethyls microballoon (being purchased from U.S. Bangs Laboratories, INC) is added into 20ml mass
Fraction is in 10% 1,6- hexamethylene diamine solution, and stirring reaction is removed after 12 hours through dialysis or hollow fiber conduit cleaning at 90 DEG C
Unreacted small molecule is gone, obtains ammonification microballoon；
B, the aldehydedodextrans freeze-dried powder in 2.5g embodiments 1 is taken to be dissolved in 50ml phosphate buffers, it is described
The concentration of phosphate buffer is 0.1mol/L, the pH=6.0 of the phosphate buffer, adds the ammonification microballoon, mixing
Three hydrogen boron sodium cyanide solutions are slowly added dropwise after uniformly, the three hydrogen boron sodium cyanide solution is that the hydrogen boron Cymags of 0.4g tri- are dissolved in
Obtain in 2.5ml 0.1mol/L phosphate buffers, reacted 12 hours at 37 DEG C；
C, eccentric cleaning removes unreacted small molecule and constant volume is into 50ml, obtains 0.9g and is coated with the micro- of aldehydedodextrans
Ball.
Embodiment 5
A kind of method for coating based on aldehydedodextrans described in embodiment 2, comprises the following steps：
A, at 70 DEG C, 15g epoxy ethyls microballoon (being purchased from U.S. Bangs Laboratories, INC) is added into 10ml matter
Measure in 1, the 6- hexamethylene diamine solution that fraction is 10%, stirring reaction is cleaned after 16 hours through dialysis or hollow fiber conduit at 90 DEG C
Unreacted small molecule is removed, obtains ammonification microballoon；
B, the aldehydedodextrans freeze-dried powder in 2g embodiments 2 is taken to be dissolved in 60ml phosphate buffers, the phosphorus
The concentration of phthalate buffer is 0.1mol/L, the pH=6.0 of the phosphate buffer, adds the ammonification microballoon, and mixing is equal
Three hydrogen boron sodium cyanide solutions are slowly added dropwise after even, the three hydrogen boron sodium cyanide solution is that the hydrogen boron Cymags of 0.4g tri- are dissolved in 2.5ml
0.1mol/L phosphate buffers in obtain, reacted 8 hours at 37 DEG C；
C, eccentric cleaning removes unreacted small molecule and constant volume is into 50ml, obtains 1.35g and is coated with aldehydedodextrans
Microballoon.
Embodiment 6
A kind of method for coating based on aldehydedodextrans described in embodiment 3, comprises the following steps：
A, at 70 DEG C, 0.5g epoxy ethyls microballoon (being purchased from U.S. Bangs Laboratories, INC) is added into 30ml matter
Measure in 1, the 6- hexamethylene diamine solution that fraction is 10%, stirring reaction is removed after 8 hours through dialysis or hollow fiber conduit cleaning at 90 DEG C
Unreacted small molecule is gone, obtains ammonification microballoon；
B, the aldehydedodextrans freeze-dried powder in 3g embodiments 3 is taken to be dissolved in 40ml phosphate buffers, the phosphorus
The concentration of phthalate buffer is 0.1mol/L, the pH=6.0 of the phosphate buffer, adds the ammonification microballoon, and mixing is equal
Three hydrogen boron sodium cyanide solutions are slowly added dropwise after even, the three hydrogen boron sodium cyanide solution is that the hydrogen boron Cymags of 0.4g tri- are dissolved in 2.5ml
0.1mol/L phosphate buffers in obtain, reacted 16 hours at 37 DEG C；
C, eccentric cleaning removes unreacted small molecule and constant volume is into 50ml, obtains 0.45g and is coated with aldehydedodextrans
Microballoon.
Embodiment 7
A kind of preparation method of microsphere composition, comprises the following steps：
A, prepared by oxygen microballoon：With the method in Patent No. US 5780646 embodiment by 200mg dimethyl
Thiophene, β-two butanone and 100mg rare earth compoundings are put into microballoon (being purchased from U.S. Bangs Laboratories, INC), are formed
By oxygen microballoon；The rare earth compounding is europium complex；
B, the preparation of microballoon is supplied oxygen：With the method in Patent No. US 5780646 embodiment, by 200mg sensitising agents
It is put into microballoon, forms oxygen supply microballoon；The sensitising agent is the releasable singlet according to disclosed in United States Patent (USP) US 5709994
The chlorophyll A of oxygen；
C, aldehydedodextrans coating microballoon：At 70 DEG C, by the 1g quality point that 20ml is added by oxygen microballoon or oxygen supply microballoon
Number is in 10% 1,6- hexamethylene diamine solution, stirring reaction removes through dialysis or hollow fiber conduit cleaning at 90 DEG C after 12 hours
Unreacted small molecule, obtain ammonification microballoon；Aldehydedodextrans in 2.5g embodiments 1 are dissolved in 50ml phosphate-buffered
In liquid, the concentration of the phosphate buffer is 0.1mol/L, the pH=6.0 of the phosphate buffer, adds the ammonification
Microballoon, is added dropwise three hydrogen boron sodium cyanide solutions after well mixed, the three hydrogen boron sodium cyanide solution is 0.4g three hydrogen boron Cymags
It is dissolved in 2.5ml 0.1mol/L phosphate buffers and obtains, is reacted 12 hours at 37 DEG C；Eccentric cleaning removes unreacted small
Molecule and constant volume into 50ml, obtain being coated with aldehydedodextrans by oxygen microballoon or oxygen supply microballoon；
D, it is described to be combined as microsphere composition by oxygen microballoon and oxygen supply microballoon.
Embodiment 8
A kind of preparation method of microsphere composition, comprises the following steps：
A, prepared by oxygen microballoon：With the method in Patent No. US 5780646 embodiment by 200mg dimethyl
Thiophene, β-two butanone and 100mg rare earth compoundings are put into microballoon (being purchased from U.S. Bangs Laboratories, INC), are formed
By oxygen microballoon；The rare earth compounding is europium complex；
B, the preparation of microballoon is supplied oxygen：With the method in Patent No. US 5780646 embodiment, by 200mg sensitising agents
It is put into microballoon, forms oxygen supply microballoon；The sensitising agent is the photooxidation dye substance according to disclosed in United States Patent (USP) US 5709994
Methylene blue；
C, aldehydedodextrans coating microballoon：At 70 DEG C, by the 0.5g quality that 30ml is added by oxygen microballoon or oxygen supply microballoon
Fraction is in 10% 1,6- hexamethylene diamine solution, and stirring reaction removes after 8 hours through dialysis or hollow fiber conduit cleaning at 90 DEG C
Unreacted small molecule, obtain ammonification microballoon；Aldehydedodextrans in 3g embodiments 2 are dissolved in 40ml phosphate buffer
In, the concentration of the phosphate buffer is 0.1mol/L, the pH=6.0 of the phosphate buffer, it is micro- to add the ammonification
Ball, is added dropwise three hydrogen boron sodium cyanide solutions after well mixed, the three hydrogen boron sodium cyanide solution is that 0.4g three hydrogen boron Cymags are molten
Obtain in 2.5ml 0.1mol/L phosphate buffers, reacted 16 hours at 37 DEG C；Eccentric cleaning removes unreacted small point
Son and constant volume is into 50ml, obtain being coated with aldehydedodextrans by oxygen microballoon or oxygen supply microballoon；
D, it is described to be combined as microsphere composition by oxygen microballoon and oxygen supply microballoon.
Embodiment 9
A kind of preparation method of microsphere composition, comprises the following steps：
A, prepared by oxygen microballoon：With the method in Patent No. US 5780646 embodiment by 200mg dimethyl
Thiophene, β-two butanone and 100mg rare earth compoundings are put into microballoon (being purchased from U.S. Bangs Laboratories, INC), are formed
By oxygen microballoon；The rare earth compounding is terbium coordination compound；
B, the preparation of microballoon is supplied oxygen：With the method in Patent No. US 5780646 embodiment, by 200mg sensitising agents
It is put into microballoon, forms oxygen supply microballoon；The sensitising agent is the photooxidation dye substance according to disclosed in United States Patent (USP) US 5709994
Rose-red；
C, aldehydedodextrans coating microballoon：At 70 DEG C, by the 1.5g quality that 10ml is added by oxygen microballoon or oxygen supply microballoon
Fraction is in 10% 1,6- hexamethylene diamine solution, and stirring reaction is removed after 16 hours through dialysis or hollow fiber conduit cleaning at 90 DEG C
Unreacted small molecule is gone, obtains ammonification microballoon；Aldehydedodextrans in 2g embodiments 3 are dissolved in 60ml phosphate-buffered
In liquid, the concentration of the phosphate buffer is 0.1mol/L, the pH=6.0 of the phosphate buffer, adds the ammonification
Microballoon, is added dropwise three hydrogen boron sodium cyanide solutions after well mixed, the three hydrogen boron sodium cyanide solution is 0.4g three hydrogen boron Cymags
It is dissolved in 2.5ml 0.1mol/L phosphate buffers and obtains, is reacted 8 hours at 37 DEG C；Eccentric cleaning removes unreacted small
Molecule and constant volume into 50ml, obtain being coated with aldehydedodextrans by oxygen microballoon or oxygen supply microballoon；
D, it is described to be combined as microsphere composition by oxygen microballoon and oxygen supply microballoon.
Embodiment 10
A kind of preparation method of microsphere composition, comprises the following steps：
A, the synthetic method of europium complex：4.8g adjacent phenyl biphenyl is dissolved in 40ml anhydrous methylene chloride, added
Enter 5.88g aluminium chloride, be cooled to 0 DEG C；4g chloroacetic chloride is added dropwise, is reacted at room temperature 1.5 hours after being added dropwise, by system
After organic phase is washed with water three times, 5.2g solids I is obtained with anhydrous sodium sulfate drying；Solids I described in 3.2g is taken to be dissolved in
In 40ml absolute ether, 2g sodium methoxides and 4g Trifluoroacetic Acid Ethyl Esters are added, is reacted at room temperature 2.5 hours, will be organic in system
After being mutually washed with water three times, 1.6g solids II is obtained with anhydrous sodium sulfate drying；By the trichloride hydrate europiums of 2.932g six with
Solids II described in 6.39g is well mixed, adds the dissolving of 40ml absolute ethyl alcohols, and stirring adds 2ml ammoniacal liquor to pH to 8, and room temperature is anti-
After answering 1 hour, 800ml water is added into system, precipitation is collected by filtration, and precipitation is dried to obtain 9g solids III；Take 4.0g
4,7- diphenyl -1,10- phenanthroline (DPP) are dissolved by heating in 120ml ethanol, and recrystallization crystal is collected after cooling；Take 3.014g
The recrystallization crystal and 0.997g 4,7- diphenyl -1,10- phenanthroline are added in 300ml toluene, and it is small that 1.5 are stirred at 62 DEG C
When, room temperature is cooled to, except toluene, obtains europium complex.
B, the synthetic method of thioxene and β-two butanone：34.4g bromoanilines are dissolved in 125ml DMF, added
Enter 0.6mol bromotetradecanes and 0.6mol diisopropylethylamine, after 100 DEG C are reacted 12 hours, 300ml is added into reaction solution
Dichloromethane, after system is washed with water three times, add ethyl alcohol recrystallization, obtain N, the dibasic para-bromoaniline of N-；By described in
The dibasic para-bromoaniline of N, N-, 3g magnesium rods and iodine are dissolved in wiring solution-forming in 50ml THF, under the conditions of maintaining the reflux for, by solution
It is added drop-wise in 100ml THF, back flow reaction 1 hour after liquid feeding, is cooled to 0 DEG C, 0.1mol peroxide benzene is added into system
Formic acid and 50ml THF, react 2.5 hours at room temperature；It is 0.1mol/L hydrochloric acid to hydrolyze that molar concentration is slowly added into system
After the salt of generation, 200ml dichloromethane is added into system, after the organic phase in system is washed with water three times, with anhydrous sulphur
Sour sodium is dried, and column chromatography for separation obtains intermediate；The intermediate is dissolved in 100ml toluene solution, adds zinc chloride
With 0.11mol 2 mercapto ethanols, back flow reaction 4 hours, Rotary Evaporators remove toluene, column chromatography obtain thioxene and
β-two butanone.
C, prepared by oxygen microballoon：With the method in Patent No. US 5780646 embodiment by described in 200mg two
Methylthiophene, β-two butanone and europium complex described in 100mg are put into microballoon (being purchased from U.S. Bangs Laboratories, INC)
In, formed by oxygen microballoon；
D, the preparation of microballoon is supplied oxygen：With the method in Patent No. US 5780646 embodiment, by 200mg sensitising agents
It is put into microballoon, forms oxygen supply microballoon；The sensitising agent is the releasable singlet according to disclosed in United States Patent (USP) US 5709994
The chlorophyll A of oxygen；
E, aldehydedodextrans coating microballoon：At 70 DEG C, by the 1g quality point that 20ml is added by oxygen microballoon or oxygen supply microballoon
Number is in 10% 1,6- hexamethylene diamine solution, stirring reaction removes through dialysis or hollow fiber conduit cleaning at 90 DEG C after 12 hours
Unreacted small molecule, obtain ammonification microballoon；Aldehydedodextrans in 2.5g embodiments 1 are dissolved in 50ml phosphate-buffered
In liquid, the concentration of the phosphate buffer is 0.1mol/L, the pH=6.0 of the phosphate buffer, adds the ammonification
Microballoon, is added dropwise three hydrogen boron sodium cyanide solutions after well mixed, the three hydrogen boron sodium cyanide solution is 0.4g three hydrogen boron Cymags
It is dissolved in 2.5ml 0.1mol/L phosphate buffers and obtains, is reacted 12 hours at 37 DEG C；Eccentric cleaning removes unreacted small
Molecule and constant volume into 50ml, obtain being coated with aldehydedodextrans by oxygen microballoon or oxygen supply microballoon；
F, it is described to be combined as microsphere composition by oxygen microballoon and oxygen supply microballoon.
Embodiment 11
A kind of preparation method of microsphere composition, comprises the following steps：
C, the synthetic method of europium complex：4.5g adjacent phenyl biphenyl is dissolved in 50ml anhydrous methylene chloride, added
Enter 5.50g aluminium chloride, be cooled to 0 DEG C；4.5g chloroacetic chloride is added dropwise, is reacted at room temperature 1 hour after being added dropwise, by system
After organic phase is washed with water three times, 5.0g solids I is obtained with anhydrous sodium sulfate drying；Solids I described in 3.5g is taken to be dissolved in
In 30ml absolute ether, 2.5g sodium methoxides and 3g Trifluoroacetic Acid Ethyl Esters are added, is reacted at room temperature 3 hours, will be organic in system
After being mutually washed with water three times, 2.0g solids II is obtained with anhydrous sodium sulfate drying；By the trichloride hydrate europiums of 2.800g six with
Solids II described in 6.00g is well mixed, adds the dissolving of 50ml absolute ethyl alcohols, and stirring adds 1.5ml ammoniacal liquor to pH to 7, room temperature
After reaction 1 hour, 1000ml water is added into system, precipitation is collected by filtration, and precipitation is dried to obtain 10g solids III；Take
3.0g 4,7- diphenyl -1,10- phenanthroline (DPP) are dissolved by heating in 150ml ethanol, and recrystallization crystal is collected after cooling；Take
Crystal and 1.200g 4 are recrystallized described in 2.500g, 7- diphenyl -1,10- phenanthroline is added in 200ml toluene, stirred at 62 DEG C
2 hours, room temperature is cooled to, except toluene, obtains europium complex.
D, the synthetic method of thioxene and β-two butanone：30.0g bromoanilines are dissolved in 150ml DMF, added
Enter 0.45mol bromotetradecanes and 0.8mol diisopropylethylamine, after 100 DEG C are reacted 12 hours, 200ml is added into reaction solution
Dichloromethane, after system is washed with water three times, add ethyl alcohol recrystallization, obtain N, the dibasic para-bromoaniline of N-；By described in
The dibasic para-bromoaniline of N, N-, 3.5g magnesium rods and iodine are dissolved in wiring solution-forming in 40ml THF, will be molten under the conditions of maintaining the reflux for
Drop is added in 120ml THF, back flow reaction 1 hour after liquid feeding, is cooled to 0 DEG C, and 0.8mol peroxides are added into system
Benzoic acid and 60ml THF, react 2 hours at room temperature；It is 0.1mol/L hydrochloric acid to hydrolyze that molar concentration is slowly added into system
After the salt of generation, 250ml dichloromethane is added into system, after the organic phase in system is washed with water three times, with anhydrous sulphur
Sour sodium is dried, and column chromatography for separation obtains intermediate；The intermediate is dissolved in 80ml toluene solution, add zinc chloride and
0.13mol 2 mercapto ethanols, back flow reaction 3 hours, Rotary Evaporators remove toluene, column chromatography obtain thioxene and β-
Two butanone.
C, prepared by oxygen microballoon：With the method in Patent No. US 5780646 embodiment by 200mg dimethyl
Thiophene, β-two butanone and europium complex described in 100mg are put into microballoon (being purchased from U.S. Bangs Laboratories, INC), shape
Into by oxygen microballoon；
D, the preparation of microballoon is supplied oxygen：With the method in Patent No. US 5780646 embodiment, by 200mg sensitising agents
It is put into microballoon, forms oxygen supply microballoon；The sensitising agent is the photooxidation dye substance according to disclosed in United States Patent (USP) US 5709994
Methylene blue；
E, aldehydedodextrans coating microballoon：At 70 DEG C, by the 0.5g quality that 30ml is added by oxygen microballoon or oxygen supply microballoon
Fraction is in 10% 1,6- hexamethylene diamine solution, and stirring reaction removes after 8 hours through dialysis or hollow fiber conduit cleaning at 90 DEG C
Unreacted small molecule, obtain ammonification microballoon；Aldehydedodextrans in 3g embodiments 2 are dissolved in 40ml phosphate buffer
In, the concentration of the phosphate buffer is 0.1mol/L, the pH=6.0 of the phosphate buffer, it is micro- to add the ammonification
Ball, is added dropwise three hydrogen boron sodium cyanide solutions after well mixed, the three hydrogen boron sodium cyanide solution is that 0.4g three hydrogen boron Cymags are molten
Obtain in 2.5ml 0.1mol/L phosphate buffers, reacted 16 hours at 37 DEG C；Eccentric cleaning removes unreacted small point
Son and constant volume is into 50ml, obtain being coated with aldehydedodextrans by oxygen microballoon or oxygen supply microballoon；
F, it is described to be combined as microsphere composition by oxygen microballoon and oxygen supply microballoon.
Embodiment 12
A kind of preparation method of microsphere composition, comprises the following steps：
E, the synthetic method of europium complex：5.0g adjacent phenyl biphenyl is dissolved in 30ml anhydrous methylene chloride, added
Enter 6.00g aluminium chloride, be cooled to 0 DEG C；3.5g chloroacetic chloride is added dropwise, is reacted at room temperature 2 hours after being added dropwise, by system
After organic phase is washed with water three times, 6.0g solids I is obtained with anhydrous sodium sulfate drying；Solids I described in 3.0g is taken to be dissolved in
In 50ml absolute ether, 1.5g sodium methoxides and 5g Trifluoroacetic Acid Ethyl Esters are added, is reacted at room temperature 2 hours, will be organic in system
After being mutually washed with water three times, 1.0g solids II is obtained with anhydrous sodium sulfate drying；By the trichloride hydrate europiums of 3.200g six with
Solids II described in 6.80g is well mixed, adds the dissolving of 30ml absolute ethyl alcohols, and stirring adds 2.5ml ammoniacal liquor to pH to 9, room temperature
After reaction 1 hour, 600ml water is added into system, precipitation is collected by filtration, and precipitation is dried to obtain 11g solids III；Take
5.0g 4,7- diphenyl -1,10- phenanthroline (DPP) are dissolved by heating in 100ml ethanol, and recrystallization crystal is collected after cooling；Take
Crystal and 0.800g 4 are recrystallized described in 3.500g, 7- diphenyl -1,10- phenanthroline is added in 400ml toluene, stirred at 62 DEG C
1 hour, room temperature is cooled to, except toluene, obtains europium complex.
F, the synthetic method of thioxene and β-two butanone：40.0g bromoanilines are dissolved in 100ml DMF, added
Enter 0.8mol bromotetradecanes and 0.45mol diisopropylethylamine, after 100 DEG C are reacted 12 hours, 400ml is added into reaction solution
Dichloromethane, after system is washed with water three times, add ethyl alcohol recrystallization, obtain N, the dibasic para-bromoaniline of N-；By described in
The dibasic para-bromoaniline of N, N-, 2.5g magnesium rods and iodine are dissolved in wiring solution-forming in 60ml THF, will be molten under the conditions of maintaining the reflux for
Drop is added in 80ml THF, back flow reaction 1 hour after liquid feeding, is cooled to 0 DEG C, and 0.12mol peroxides are added into system
Benzoic acid and 40ml THF, react 3 hours at room temperature；It is 0.1mol/L hydrochloric acid to hydrolyze that molar concentration is slowly added into system
After the salt of generation, 150ml dichloromethane is added into system, after the organic phase in system is washed with water three times, with anhydrous sulphur
Sour sodium is dried, and column chromatography for separation obtains intermediate；The intermediate is dissolved in 120ml toluene solution, adds zinc chloride
With 0.09mol 2 mercapto ethanols, back flow reaction 5 hours, Rotary Evaporators remove toluene, column chromatography obtain thioxene and
β-two butanone.
C, prepared by oxygen microballoon：With the method in Patent No. US 5780646 embodiment by 200mg dimethyl
Thiophene, β-two butanone and europium complex described in 100mg are put into microballoon (being purchased from U.S. Bangs Laboratories, INC), shape
Into by oxygen microballoon；
D, the preparation of microballoon is supplied oxygen：With the method in Patent No. US 5780646 embodiment, by 200mg sensitising agents
It is put into microballoon, forms oxygen supply microballoon；The sensitising agent is the photooxidation dye substance according to disclosed in United States Patent (USP) US 5709994
Phthalocyanine compound；
E, aldehydedodextrans coating microballoon：At 70 DEG C, by the 1.5g quality that 10ml is added by oxygen microballoon or oxygen supply microballoon
Fraction is in 10% 1,6- hexamethylene diamine solution, and stirring reaction is removed after 16 hours through dialysis or hollow fiber conduit cleaning at 90 DEG C
Unreacted small molecule is gone, obtains ammonification microballoon；Aldehydedodextrans in 2g embodiments 3 are dissolved in 60ml phosphate-buffered
In liquid, the concentration of the phosphate buffer is 0.1mol/L, the pH=6.0 of the phosphate buffer, adds the ammonification
Microballoon, is added dropwise three hydrogen boron sodium cyanide solutions after well mixed, the three hydrogen boron sodium cyanide solution is 0.4g three hydrogen boron Cymags
It is dissolved in 2.5ml 0.1mol/L phosphate buffers and obtains, is reacted 8 hours at 37 DEG C；Eccentric cleaning removes unreacted small
Molecule and constant volume into 50ml, obtain being coated with aldehydedodextrans by oxygen microballoon or oxygen supply microballoon；
F, it is described to be combined as microsphere composition by oxygen microballoon and oxygen supply microballoon.
It should be noted last that the above embodiments are merely illustrative of the technical solutions of the present invention and it is unrestricted, although ginseng
The present invention is described in detail according to preferred embodiment, should be understood that the specific implementation that the foregoing is only the present invention
Mode, the protection domain being not intended to limit the present invention, within the spirit and principles of the invention, that is done any repaiies
Change, equivalent substitution, improvement etc., should be included in the scope of the protection.
Claims (10)
1. a kind of synthetic method of aldehydedodextrans, it is characterised in that comprise the following steps：
A, after glucan being dissolved in into water, under inert gas shielding, EDTA, 1, 4-benzenediol, sodium borohydride, NaOH and first are added
Benzene, it is stirred at reflux 1-3 hours；
B, bromo- 1, the 1- diethoxyethane solution of 2- is added dropwise into system, time for adding is no less than 1 hour；After being added dropwise to complete, stir
Mix backflow 12-18 hours；
C, the organic phase in system is washed with water, obtains the aqueous solution, the aqueous solution is added in methanol, obtains hydroformylation sugar precursor
Precipitation；
D, it is hydroformylation sugar precursor precipitation is soluble in water, add toluenesulfonic acid and adjust pH to 1-2, after heating hydrolysis, use NaOH
Solution is adjusted to neutrality, and aldehydedodextrans are obtained in the form of precipitation.
2. the synthetic method of aldehydedodextrans according to claim 1, it is characterised in that comprise the following steps：
A, after the glucan of 20000-40000 parts by weight being dissolved in the water of 50-130 parts by volume, under nitrogen protection, 5-15 is added
The 1, 4-benzenediols of EDTA, 5-15 parts by weight of parts by weight, the sodium borohydride of 5-15 parts by weight, 4000-8000 parts by weight
The toluene of NaOH and 40-80 parts by volume, it is stirred at reflux 1-3 hours；
B, the toluene solution of bromo- 1, the 1- diethoxyethane of 2- is added dropwise into system, time for adding is no less than 1 hour, 2- bromo- 1,
The volume ratio of 1- diethoxyethane and toluene is 1:4-5；After being added dropwise to complete, 12-18 hours are stirred at reflux；
C, after being cooled to room temperature, the organic phase in system is washed with water three times, the volume of water used is 120-180 volumes every time
Part, merge aqueous phase and obtain the aqueous solution, the aqueous solution is added in the methanol of 1500-2500 parts by volume, washed after suction filtration with ethanol
Three times, the volume of ethanol used is 200-280 parts by volume every time, and washed precipitation is dried in vacuo, before obtaining hydroformylation sugar
Body precipitates；
D, the hydroformylation sugar precursor precipitation of 5000-15000 parts by weight is dissolved in the water of 30-70 parts by volume, adds toluene sulphur
Acid adjusts pH to 1-2, is heated to 70-90 DEG C and is hydrolyzed, and after hydrolyzing 1-3 hours, use quality fraction is that 30-50% NaOH is molten
Liquid is adjusted to neutrality, and after filtering, removal of impurities, aldehydedodextrans are obtained in the form of precipitation；
In methods described, parts by weight/parts by volume is：g/L.
A kind of 3. method for coating for the aldehydedodextrans that synthetic method of claim 1 or 2 obtains, it is characterised in that
Comprise the following steps：
A, microballoon is added in 1,6- hexamethylene diamine solution, reacts 8-16 hours, obtain ammonification microballoon；
B, the aldehydedodextrans are dissolved in phosphate buffer, add the ammonification microballoon, three are added dropwise after well mixed
Hydrogen boron sodium cyanide solution, react 8-16 hours；
C, eccentric cleaning, obtain being coated with the microballoon of aldehydedodextrans.
4. method for coating according to claim 3, it is characterised in that comprise the following steps：
A, it is 10% by the mass fraction that the epoxy ethyl microballoon of 500-1500 parts by weight adds 10-30 parts by volume at 70 DEG C
In 1,6- hexamethylene diamine solution, at 90 DEG C after stirring reaction 8-16 hours, removed through dialysis or hollow fiber conduit cleaning unreacted
Small molecule, obtain ammonification microballoon；
B, the aldehydedodextrans of 2000-3000 parts by weight are dissolved in the phosphate buffer of 40-60 parts by volume, it is described
The concentration of phosphate buffer is 0.1mol/L, the pH=6.0 of the phosphate buffer, adds the ammonification microballoon, mixing
Three hydrogen boron sodium cyanide solutions are added dropwise after uniformly, the three hydrogen boron sodium cyanide solution is dissolved in for three hydrogen boron Cymags of 400 parts by weight
Obtained in the 0.1mol/L phosphate buffers of 2.5 parts by volume, 8-16 hours are reacted at 37 DEG C；
C, eccentric cleaning removes unreacted small molecule, obtains being coated with the microballoon of aldehydedodextrans；
In methods described, parts by weight/parts by volume is：g/L.
5. a kind of usage right requires the method that the aldehydedodextrans that 1 or 2 synthetic methods obtain prepare microsphere composition, its
It is characterised by, comprises the following steps：
A, prepared by oxygen microballoon：Thioxene, β-two butanone and rare earth compounding are put into microballoon, formed micro- by oxygen
Ball；
B, the preparation of microballoon is supplied oxygen：Sensitising agent is put into microballoon, forms oxygen supply microballoon；
C, aldehydedodextrans coating microballoon：It will be added by oxygen microballoon or oxygen supply microballoon in 1,6- hexamethylene diamine solution, reaction 8-16 is small
When, obtain ammonification microballoon；The aldehydedodextrans are dissolved in phosphate buffer, add the ammonification microballoon, mixing is equal
Three hydrogen boron sodium cyanide solutions are added dropwise after even, react 8-16 hours；Eccentric cleaning, obtain being coated with aldehydedodextrans by oxygen microballoon
Or oxygen supply microballoon；
D, it is described to be combined as microsphere composition by oxygen microballoon and oxygen supply microballoon.
6. the preparation method of microsphere composition according to claim 5, it is characterised in that comprise the following steps：
A, prepared by oxygen microballoon：Thioxene, β-two butanone and rare earth compounding are put into microballoon, formed micro- by oxygen
Ball；
B, the preparation of microballoon is supplied oxygen：Sensitising agent is put into microballoon, forms oxygen supply microballoon；
C, aldehydedodextrans coating microballoon：At 70 DEG C, 500-1500 parts by weight are added into 10-30 by oxygen microballoon or oxygen supply microballoon
The mass fraction of parts by volume be 10% 1,6- hexamethylene diamine solution in, at 90 DEG C after stirring reaction 8-16 hours, through dialysis or in
The cleaning of hollow fiber pipe removes unreacted small molecule, obtains ammonification microballoon；By the aldehydedodextrans of 2000-3000 parts by weight
It is dissolved in the phosphate buffer of 40-60 parts by volume, the concentration of the phosphate buffer is 0.1mol/L, the phosphate
The pH=6.0 of buffer solution, the ammonification microballoon is added, three hydrogen boron sodium cyanide solutions, the three hydrogen boron cyanogen is added dropwise after well mixed
Change sodium solution is dissolved in the 0.1mol/L phosphate buffers of 2.5 parts by volume for three hydrogen boron Cymags of 400 parts by weight to be obtained, and 37
8-16 hours are reacted at DEG C；Eccentric cleaning removes unreacted small molecule, obtain being coated with aldehydedodextrans by oxygen microballoon or
Supply oxygen microballoon；
D, it is described to be combined as microsphere composition by oxygen microballoon and oxygen supply microballoon；
In methods described, parts by weight/parts by volume is：g/L.
7. the preparation method of the microsphere composition according to claim 5 or 6, it is characterised in that the rare earth compounding is
Europium complex or terbium coordination compound；The sensitising agent be methylene blue, rose-red, phthalocyanine compound and chlorophyll A in one kind or
Combination.
8. the preparation method of microsphere composition according to claim 7, it is characterised in that the synthesis side of the europium complex
Method comprises the following steps：
A, adjacent phenyl biphenyl is dissolved in dichloromethane, is added aluminium chloride, is cooled to 0 DEG C；Chloroacetic chloride is added dropwise, rear chamber is added dropwise
Temperature reaction 1-2 hours, it is dried to obtain solids I；
B, the solids I is dissolved in absolute ether, adds sodium methoxide and Trifluoroacetic Acid Ethyl Ester, react at room temperature 2-3 hours,
It is dried to obtain solids II；
C, six trichloride hydrate europiums are well mixed with the solids II, add absolute ethyl alcohol dissolving, stirring adds ammoniacal liquor extremely
PH to 7-9, after reacting at room temperature 1-2 hours, water is added into system, filter, be dried to obtain solids III；
D, take 4,7- diphenyl -1,10- phenanthroline to dissolve by heating and recrystallization crystal is collected after ethanol, cooling；Take the heavy knot
Jingjing body and 4,7- diphenyl -1,10- phenanthroline are added in toluene, are stirred 1-2 hours, are cooled to room temperature, except toluene, obtain europium
Complex.
9. the preparation method of microsphere composition according to claim 8, it is characterised in that the synthesis side of the europium complex
Method comprises the following steps
A, the adjacent phenyl biphenyl of 4500-5000 parts by weight is dissolved in the anhydrous methylene chloride of 30-50 parts by volume, added
The aluminium chloride of 5500-6000 parts by weight, it is cooled to 0 DEG C；The chloroacetic chloride of 3500-4500 parts by weight is added dropwise, rear room temperature is added dropwise
1-2 hours are reacted, after the organic phase in system is washed with water three times, 5000-6000 weight is obtained with anhydrous sodium sulfate drying
Part solids I；
B, take the solids I of 3000-3500 parts by weight to be dissolved in the absolute ether of 30-50 parts by volume, add 1500-
The sodium methoxide of 2500 parts by weight and the Trifluoroacetic Acid Ethyl Ester of 3000-5000 parts by weight, 2-3 hours are reacted at room temperature, by system
After organic phase is washed with water three times, the solids II of 1000-2000 parts by weight is obtained with anhydrous sodium sulfate drying；
C, six trichloride hydrate europiums of 2800-3200 parts by weight are mixed with the solids II of 6000-6800 parts by weight
It is even, the absolute ethyl alcohol dissolving of 30-50 parts by volume is added, stirring adds the ammoniacal liquor of 1500-2500 parts by volume to pH to 7-9, room temperature
After reaction 1 hour, the water of 600-1000 parts by volume is added into system, precipitation is collected by filtration, and precipitation is dried to obtain solid
Thing III；
D, 4,7- diphenyl -1,10- phenanthroline of 3000-5000 parts by weight is taken to dissolve by heating in the ethanol of 100-150 parts by volume,
Recrystallization crystal is collected after cooling；Take the recrystallization crystal and the 4,7- of 800-1200 parts by weight of 2500-3500 parts by weight
Diphenyl -1,10- phenanthroline is added in the toluene of 200-400 parts by volume, and 1-2 hours are stirred at 62 DEG C, room temperature are cooled to, except first
Benzene, obtain europium complex；
In methods described, parts by weight/parts by volume is：g/L.
10. the preparation method of microsphere composition according to claim 7, it is characterised in that the thioxene and β-
The synthetic method of two butanone comprises the following steps：
A, bromoaniline is dissolved in DMF, adds bromotetradecane and diisopropylethylamine, 100 DEG C of reaction 10-14 hours
Afterwards, dichloromethane is added into reaction solution, recrystallizes to obtain N, N- bis- substitutes para-bromoaniline；
B, by the N, the dibasic para-bromoaniline of N-, magnesium rod and iodine are dissolved in wiring solution-forming in THF, under the conditions of maintaining the reflux for,
Solution is added drop-wise in THF, back flow reaction 1 hour after liquid feeding, is cooled to 0 DEG C, into system add benzoyl hydroperoxide and
THF, 2-3 hours are reacted at room temperature；After hydrochloric acid is added into system to hydrolyze the salt of generation, dichloromethane is added into system,
Dry and chromatograph isolated intermediate；
C, the intermediate is dissolved in toluene solution, adds zinc chloride and 2 mercapto ethanol, back flow reaction 3-5 hours, remove
Toluene chromatographs to obtain thioxene and β-two butanone.
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| CN113045684B (en) * | 2021-03-11 | 2023-04-25 | 山西奥睿基赛生物科技有限公司 | Solid phase metal ion chelating agent, preparation method and application thereof |
| CN113621139B (en) * | 2021-08-24 | 2022-09-13 | 濮阳市盛源石油化工（集团）有限公司 | Glucan-based amphiphilic block copolymer and preparation method thereof |
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