CN117046327A - Hollow fiber membrane with good biocompatibility and application thereof - Google Patents
Hollow fiber membrane with good biocompatibility and application thereof Download PDFInfo
- Publication number
- CN117046327A CN117046327A CN202311309320.0A CN202311309320A CN117046327A CN 117046327 A CN117046327 A CN 117046327A CN 202311309320 A CN202311309320 A CN 202311309320A CN 117046327 A CN117046327 A CN 117046327A
- Authority
- CN
- China
- Prior art keywords
- hollow fiber
- fiber membrane
- aromatic
- grafted
- membrane according
- Prior art date
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- Pending
Links
- 239000012528 membrane Substances 0.000 title claims abstract description 49
- 239000012510 hollow fiber Substances 0.000 title claims abstract description 39
- 125000003118 aryl group Chemical group 0.000 claims abstract description 37
- 239000004695 Polyether sulfone Substances 0.000 claims abstract description 24
- 229920002492 poly(sulfone) Polymers 0.000 claims abstract description 24
- 229920006393 polyether sulfone Polymers 0.000 claims abstract description 24
- 229920001600 hydrophobic polymer Polymers 0.000 claims abstract description 23
- GTDPSWPPOUPBNX-UHFFFAOYSA-N ac1mqpva Chemical compound CC12C(=O)OC(=O)C1(C)C1(C)C2(C)C(=O)OC1=O GTDPSWPPOUPBNX-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000003146 anticoagulant agent Substances 0.000 claims abstract description 12
- 229940127219 anticoagulant drug Drugs 0.000 claims abstract description 12
- 229920000768 polyamine Polymers 0.000 claims abstract description 12
- 238000003756 stirring Methods 0.000 claims abstract description 12
- 150000004984 aromatic diamines Chemical class 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 8
- 239000011159 matrix material Substances 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 6
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 4
- 238000010517 secondary reaction Methods 0.000 claims abstract description 4
- 239000000243 solution Substances 0.000 claims description 33
- 238000009987 spinning Methods 0.000 claims description 22
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 229920005575 poly(amic acid) Polymers 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 229960002897 heparin Drugs 0.000 claims description 4
- 229920000669 heparin Polymers 0.000 claims description 4
- CBCKQZAAMUWICA-UHFFFAOYSA-N 1,4-phenylenediamine Chemical compound NC1=CC=C(N)C=C1 CBCKQZAAMUWICA-UHFFFAOYSA-N 0.000 claims description 3
- UPMLOUAZCHDJJD-UHFFFAOYSA-N 4,4'-Diphenylmethane Diisocyanate Chemical compound C1=CC(N=C=O)=CC=C1CC1=CC=C(N=C=O)C=C1 UPMLOUAZCHDJJD-UHFFFAOYSA-N 0.000 claims description 3
- YBRVSVVVWCFQMG-UHFFFAOYSA-N 4,4'-diaminodiphenylmethane Chemical compound C1=CC(N)=CC=C1CC1=CC=C(N)C=C1 YBRVSVVVWCFQMG-UHFFFAOYSA-N 0.000 claims description 3
- HLBLWEWZXPIGSM-UHFFFAOYSA-N 4-Aminophenyl ether Chemical compound C1=CC(N)=CC=C1OC1=CC=C(N)C=C1 HLBLWEWZXPIGSM-UHFFFAOYSA-N 0.000 claims description 3
- CQMIJLIXKMKFQW-UHFFFAOYSA-N 4-phenylbenzene-1,2,3,5-tetracarboxylic acid Chemical compound OC(=O)C1=C(C(O)=O)C(C(=O)O)=CC(C(O)=O)=C1C1=CC=CC=C1 CQMIJLIXKMKFQW-UHFFFAOYSA-N 0.000 claims description 3
- VQVIHDPBMFABCQ-UHFFFAOYSA-N 5-(1,3-dioxo-2-benzofuran-5-carbonyl)-2-benzofuran-1,3-dione Chemical compound C1=C2C(=O)OC(=O)C2=CC(C(C=2C=C3C(=O)OC(=O)C3=CC=2)=O)=C1 VQVIHDPBMFABCQ-UHFFFAOYSA-N 0.000 claims description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 3
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 claims description 3
- 238000000578 dry spinning Methods 0.000 claims description 3
- AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 claims description 3
- 125000006158 tetracarboxylic acid group Chemical group 0.000 claims description 3
- MBYLVOKEDDQJDY-UHFFFAOYSA-N tris(2-aminoethyl)amine Chemical compound NCCN(CCN)CCN MBYLVOKEDDQJDY-UHFFFAOYSA-N 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 238000002166 wet spinning Methods 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 2
- 230000010100 anticoagulation Effects 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 7
- 108010073385 Fibrin Proteins 0.000 abstract description 3
- 102000009123 Fibrin Human genes 0.000 abstract description 3
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 abstract description 3
- 108010094028 Prothrombin Proteins 0.000 abstract description 3
- 102100027378 Prothrombin Human genes 0.000 abstract description 3
- 229950003499 fibrin Drugs 0.000 abstract description 3
- 229940039716 prothrombin Drugs 0.000 abstract description 3
- 230000008021 deposition Effects 0.000 abstract description 2
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 238000000034 method Methods 0.000 description 5
- 239000000835 fiber Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 229920001002 functional polymer Polymers 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000002715 modification method Methods 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 238000005191 phase separation Methods 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 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 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000004283 Sodium sorbate Substances 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 239000013590 bulk material Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 238000002464 physical blending Methods 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940113116 polyethylene glycol 1000 Drugs 0.000 description 1
- 229940085675 polyethylene glycol 800 Drugs 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- BTURAGWYSMTVOW-UHFFFAOYSA-M sodium dodecanoate Chemical compound [Na+].CCCCCCCCCCCC([O-])=O BTURAGWYSMTVOW-UHFFFAOYSA-M 0.000 description 1
- UDWXLZLRRVQONG-UHFFFAOYSA-M sodium hexanoate Chemical compound [Na+].CCCCCC([O-])=O UDWXLZLRRVQONG-UHFFFAOYSA-M 0.000 description 1
- 229940082004 sodium laurate Drugs 0.000 description 1
- BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 1
- ZNCPFRVNHGOPAG-UHFFFAOYSA-L sodium oxalate Chemical compound [Na+].[Na+].[O-]C(=O)C([O-])=O ZNCPFRVNHGOPAG-UHFFFAOYSA-L 0.000 description 1
- 229940039790 sodium oxalate Drugs 0.000 description 1
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 description 1
- 239000004324 sodium propionate Substances 0.000 description 1
- 235000010334 sodium propionate Nutrition 0.000 description 1
- 229960003212 sodium propionate Drugs 0.000 description 1
- LROWVYNUWKVTCU-STWYSWDKSA-M sodium sorbate Chemical compound [Na+].C\C=C\C=C\C([O-])=O LROWVYNUWKVTCU-STWYSWDKSA-M 0.000 description 1
- 235000019250 sodium sorbate Nutrition 0.000 description 1
- PBDAWQLIMPWEEF-JEDNCBNOSA-M sodium;(2s)-2,6-diaminohexanoate Chemical compound [Na+].NCCCC[C@H](N)C([O-])=O PBDAWQLIMPWEEF-JEDNCBNOSA-M 0.000 description 1
- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000004804 winding Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
- B01D71/06—Organic material
- B01D71/66—Polymers having sulfur in the main chain, with or without nitrogen, oxygen or carbon only
- B01D71/68—Polysulfones; Polyethersulfones
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D67/00—Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
- B01D67/0002—Organic membrane manufacture
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
- B01D69/02—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor characterised by their properties
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
- B01D69/08—Hollow fibre membranes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D2325/00—Details relating to properties of membranes
- B01D2325/36—Hydrophilic membranes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D2325/00—Details relating to properties of membranes
- B01D2325/58—Biocompatibility of membrane
Landscapes
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Manufacturing & Machinery (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Artificial Filaments (AREA)
Abstract
The invention discloses a hollow fiber membrane with good biocompatibility, which comprises a polysulfone/polyethersulfone matrix component and a grafted aromatic hydrophobic polymer with the mass content of 30-100% of the matrix component, wherein the preparation method of the grafted aromatic hydrophobic polymer comprises the following steps: dissolving aromatic diamine in an organic solvent, adding aromatic dianhydride, performing polymerization reaction for 4-10h, adding polyamine, stirring and dissolving, performing secondary reaction for 2-4 h, and finally adding an anticoagulant containing carboxyl, and performing grafting reaction for 12-48h to obtain the grafted aromatic hydrophobic polymer. The hollow fiber membrane has stable performance, can effectively reduce deposition of prothrombin, fibrin and the like, obviously improves anticoagulation effect and greatly improves biocompatibility.
Description
Technical Field
The invention relates to the field of biological materials, in particular to a hollow fiber membrane with good biocompatibility and application thereof.
Background
Polysulfone/polyethersulfone is a polymer material with excellent comprehensive properties, has excellent heat resistance, physical and mechanical properties, insulating properties, relatively good biocompatibility and the like, and has been widely used in a plurality of fields. Polysulfone/polyethersulfone also has good film forming and filtration properties, and thus is one of the most common hollow fiber membrane preparation materials.
However, the polysulfone/polyethersulfone membrane material has strong hydrophobic effect and strong polarity of sulfur and oxygen atoms existing in the structure, so that the polysulfone/polyethersulfone membrane material has strong adhesion effect on blood platelets and the like when being applied to clinical blood contact, and the porous structure of the fibrous membrane material is easy to deposit prothrombin and fibrin in pores of the fibrous membrane, so that a coagulation system is activated, thrombus is induced to form, protein pollution is easy to occur after long-term use, and further a pore blocking phenomenon occurs.
In order to improve the anticoagulation and anti-pollution performance of the polysulfone/polyethersulfone membrane material, three methods are mainly adopted: (1) Performing body modification, namely performing anticoagulation modification on a polysulfone/polyether sulfone material body, and then preparing a fibrous membrane; (2) Surface modification, grafting self-anticoagulation polymer on the surface of the fiber by a chemical method, a photochemical method or a plasma technology, or coating the self-anticoagulation polymer on the surface by a physical method; (3) Blending modification, namely blending polysulfone/polyether sulfone with self-coagulation-resistant functional polymer to form spinning solution, and finally spinning to form a film.
The polysulfone/polyethersulfone bulk material has stable performance, is very difficult to modify, and is generally applied to hollow fiber membrane materials with smaller diameters by surface grafting and coating modification, so that the mass production and the application are difficult to realize. At present, a physical blending modification method is mainly adopted to improve the anticoagulation performance of the polysulfone/polyether sulfone fibrous membrane. For example, polyvinyl pyrrolidone (PVP), a zwitterionic compound (MPC of polyphosphoester) and a sulfonated functional polymer are mixed into a polysulfone/polyethersulfone film-forming liquid, and finally spun into a film. However, the hydrophilic additive can be slowly separated out in the use process of the hollow fiber membrane obtained by the modification method, and the performance stability is not high; even if amphiphilic polymers are used, the problem of large phase separation still exists, and the strength and mechanical properties of the fiber membrane are easily reduced, so that the filtration stability of the membrane is reduced.
Disclosure of Invention
The invention aims to overcome at least one defect of the prior art and provide a hollow fiber membrane with good biocompatibility and application thereof.
The technical scheme adopted by the invention is as follows:
in a first aspect, the present invention provides a hollow fiber membrane with good biocompatibility, the components of the hollow fiber membrane comprise a polysulfone/polyethersulfone matrix component and a grafted aromatic hydrophobic polymer with a mass content of 30% -100% of the matrix component, wherein the preparation method of the grafted aromatic hydrophobic polymer comprises the following steps:
1) Dissolving aromatic diamine in an organic solvent, adding aromatic dianhydride, and carrying out polymerization reaction for 4-10h to obtain a polyamic acid solution;
2) Adding polyamine into the polyamic acid solution prepared in the step 1), stirring and dissolving, and carrying out secondary reaction for 2-4 h;
3) Adding an anticoagulant containing carboxyl into the solution obtained in the step 2), and carrying out grafting reaction for 12-48 hours to obtain the grafted aromatic hydrophobic polymer.
In some examples, the aromatic dianhydride of step 1) is selected from any one of 3,3',4, 4' -benzophenone tetracarboxylic dianhydride, 4, 4' -hexafluoroisopropylidene-phthalic anhydride, 3',4, 4' -biphenyl tetracarboxylic dianhydride, 1, 2',4, 5' -pyromellitic anhydride, 3',4, 4' -diphenylsulfone tetracarboxylic dianhydride, or phthalic anhydride.
In some examples, the aromatic diamine of step 1) is selected from any one of 3,3' -dimethyl-4, 4' -diphenyl methane diamine, 4, 4' -diamino diphenyl methane, 4, 4' -diphenyl methane diisocyanate, or 4, 4' -diamino diphenyl ether, p-phenylenediamine.
In some examples, the molar ratio of aromatic dianhydride to aromatic diamine is: (1-1.05): 1.
in some examples, the polyamine of step 2) is selected from one or more of ethylenediamine, propylenediamine, tris (2-aminoethyl) amine, and quaternium.
In some examples, the molar ratio of the polyamine to the aromatic dianhydride is (2 to 2.05): 1.
in some examples, the organic solvent in step 1) is selected from at least one of dimethyl sulfoxide, N-methyl-2-pyrrolidone, N-dimethylformamide, and N, N-dimethylacetamide.
In some examples, the anticoagulant containing a carboxyl group is selected from heparin or heparin analogues.
In some examples, the method of making a hollow fiber membrane comprises the steps of: stirring and dissolving polysulfone/polyether sulfone, grafted aromatic hydrophobic polymer, water-soluble pore-forming agent and spinning solution solvent at 80-180 ℃, centrifugally filtering, standing at 40-80 ℃ for 2-24 hours to defoam to obtain spinning solution, and carrying out dry spinning or wet spinning, washing, stretching and drying on the spinning solution to obtain the modified hollow fiber membrane.
In some examples, the mass ratio of each component in the spinning solution is: 20-60 parts of polysulfone/polyether sulfone, 20-40 parts of grafted aromatic hydrophobic polymer, 0.1-10 parts of water-soluble pore-forming agent and 100-300 parts of spinning solution solvent.
In a second aspect, the invention provides an application of a hollow fiber membrane with good biocompatibility in preparing a blood purification material.
The beneficial effects of the invention are as follows:
according to some examples of the invention, the aromatic hydrophobic polymer grafted with the anticoagulant is blended with polysulfone/polyethersulfone for modification, and the anticoagulant group is directly obtained on the surface of the prepared hollow fiber membrane, so that the subsequent anticoagulant modification of the hollow fiber membrane is not needed, and the purpose of continuous anticoagulant modification is realized.
According to some examples of the invention, the grafted aromatic hydrophobic polymer has obvious hydrophobicity, good blending effect with polysulfone/polyethersulfone, difficult phase separation and stable performance of the hollow fiber membrane;
in some examples of the invention, the grafted aromatic hydrophobic polymer and polysulfone/polyethersulfone are blended, and the surface side branches have a large amount of amino groups, so that the hydrophilic effect of the hollow fiber membrane can be additionally improved and the biocompatibility can be improved according to the similar compatibility principle.
Detailed Description
The hollow fiber membrane with good biocompatibility comprises a polysulfone/polyethersulfone matrix component and a grafted aromatic hydrophobic polymer with the mass content of 30-100% of the matrix component, wherein the preparation method of the grafted aromatic hydrophobic polymer comprises the following steps:
1) Dissolving aromatic diamine in an organic solvent, adding aromatic dianhydride, and carrying out polymerization reaction for 4-10h to obtain a polyamic acid solution;
2) Adding polyamine into the polyamic acid solution prepared in the step 1), stirring and dissolving, and carrying out secondary reaction for 2-4 h;
3) Adding an anticoagulant containing carboxyl into the solution obtained in the step 2), and carrying out grafting reaction for 12-48 hours to obtain the grafted aromatic hydrophobic polymer.
In some examples, the aromatic dianhydride of step 1) is selected from any one of 3,3',4, 4' -benzophenone tetracarboxylic dianhydride, 4, 4' -hexafluoroisopropylidene-phthalic anhydride, 3',4, 4' -biphenyl tetracarboxylic dianhydride, 1, 2',4, 5' -pyromellitic anhydride, 3',4, 4' -diphenylsulfone tetracarboxylic dianhydride, or phthalic anhydride. The raw materials have wide sources and good stability.
In some examples, the aromatic diamine of step 1) is selected from any one of 3,3' -dimethyl-4, 4' -diphenyl methane diamine, 4, 4' -diamino diphenyl methane, 4, 4' -diphenyl methane diisocyanate, or 4, 4' -diamino diphenyl ether, p-phenylenediamine. These aromatic diamines are relatively widely available and have good stability.
In some examples, the molar ratio of aromatic dianhydride to aromatic diamine is: (1-1.05): 1, thus ensuring a sufficient reaction.
In some examples, the polyamine of step 2) is selected from one or more of ethylenediamine, propylenediamine, tris (2-aminoethyl) amine, and quaternium.
In some examples, the molar ratio of the polyamine to the aromatic dianhydride is (2 to 2.05): 1.
in some examples, the organic solvent in step 1) is selected from at least one of dimethyl sulfoxide, N-methyl-2-pyrrolidone, N-dimethylformamide, and N, N-dimethylacetamide.
The existence of carboxyl is more beneficial to the anticoagulant grafting reaction. In some examples, the anticoagulant containing a carboxyl group is selected from heparin or heparin analogues. Heparin or heparin analogues have good anticoagulation effect and safety is verified in a long-term use process.
In some examples, the method of making a hollow fiber membrane comprises the steps of: stirring and dissolving polysulfone/polyether sulfone, grafted aromatic hydrophobic polymer, water-soluble pore-forming agent and spinning solution solvent at 80-180 ℃, centrifugally filtering, standing at 40-80 ℃ for 2-24 hours to defoam to obtain spinning solution, and carrying out dry spinning or wet spinning, washing, stretching and drying on the spinning solution to obtain the modified hollow fiber membrane.
In some examples, the mass ratio of each component in the spinning solution is: 20-60 parts of polysulfone/polyether sulfone, 20-40 parts of grafted aromatic hydrophobic polymer, 0.1-10 parts of water-soluble pore-forming agent and 100-300 parts of spinning solution solvent.
The following disclosure provides many different embodiments, or examples, for implementing different aspects of the invention.
The preparation method of the grafted aromatic hydrophobic polymer of examples 1 to 3 in the present invention is as follows:
1. and (3) measuring a certain amount of strong polar solvent, gradually adding a certain amount of diamine under the protection of nitrogen, stirring for 2 hours until the diamine is completely dissolved, gradually adding dianhydride, and stirring for 4-10 hours to obtain the polyamic acid stock solution. Wherein each substance and the content thereof are shown in the following table 1.
2. Adding polyamine to the solution obtained in the step (1), wherein the molar ratio of the polyamine to the aromatic dianhydride in the step (1) is 2.05:1, stirring for 2 hours to dissolve, and then continuing stirring for 4-10 hours.
3. Adding 10mg of heparin/heparin analogue into the solution obtained in the step (2), fully stirring and dissolving, and soaking for 12-48 hours to obtain the aromatic hydrophobic polymer solution.
TABLE 1
The preparation methods of the modified hollow fiber membranes in the examples and comparative examples of the present invention are as follows:
1) According to the raw material components and mass ratio in Table 2, polysulfone/polyether sulfone, blending resin, water-soluble pore-forming agent and spinning solution solvent are respectively weighed, stirred and dissolved at 100 ℃ to form transparent solution, centrifugally filtered, and kept stand at 80 ℃ for 4 hours to defoam to obtain spinning solution.
2) Extruding the spinning solution obtained in the step 1 from a spinneret at an extrusion speed of 3-15mL/min by using spinning equipment, performing air bath of 5-50cm in air, performing solidification molding in a water bath of 20-50 ℃, winding and molding at a speed of 5-50m/min, soaking the molded fiber filaments in water, removing residual solvent and unreacted raw materials, and drying to obtain the hollow fiber membrane.
Wherein the water-soluble pore-forming agent can be at least one selected from polyethylenimine, polyethylene glycol 800, polyethylene glycol 1000, polyethylene glycol 2000, polyvinylpyrrolidone, polyacrylic acid, polyvinyl alcohol, tween-20, tween-60, tween-80, sodium sorbate, potassium sorbate, sodium citrate, sodium laurate, sodium alginate, sodium lysinate, sodium ethylenediamine tetraacetate, sodium N-tetradecanecarbonate, sodium dodecylsulfonate, sodium octoate, sodium caproate, sodium propionate, sodium acetate, sodium oxalate, lithium acetate, sodium chloride, lithium chloride, calcium chloride or copper chloride, and the spinning solution solvent is at least one selected from dimethyl sulfoxide, N-methyl-2-pyrrolidone, N-dimethylformamide and N, N-dimethylacetamide.
TABLE 2
Performance tests were then performed on examples 4-7 and comparative examples 1-2, with the test results shown in table 3 below:
TABLE 3 Table 3
Conclusion:
it can be seen that the hollow fiber membrane prepared by the invention has no obvious change in ultrafiltration coefficient and does not affect dialysis performance compared with the fiber membrane of comparative example 1 which is not subjected to hydrophilic modification; the water contact angle is obviously reduced, and the hydrophilicity is obviously improved; the pure water flux recovery rate is obviously improved after hemodialysis, which indicates that the modified hollow fiber membrane reduces deposition of prothrombin, fibrin and the like; APTT (activated partial thromboplastin time) is obviously prolonged and anticoagulation effect is obviously improved.
The hydrophilicity and anticoagulation effect are also increased to some extent as compared with a hollow fiber membrane modified with only polyvinylpyrrolidone.
The above description of the present invention is further illustrated in detail and should not be taken as limiting the practice of the present invention. It is within the scope of the present invention for those skilled in the art to make simple deductions or substitutions without departing from the concept of the present invention.
Claims (10)
1. The hollow fiber membrane with good biocompatibility is characterized in that the components of the hollow fiber membrane comprise polysulfone/polyethersulfone matrix components and grafted aromatic hydrophobic polymers with the mass content of 30% -100% of the matrix components, wherein the preparation method of the grafted aromatic hydrophobic polymers comprises the following steps:
1) Dissolving aromatic diamine in an organic solvent, adding aromatic dianhydride, and carrying out polymerization reaction for 4-10h to obtain a polyamic acid solution;
2) Adding polyamine into the polyamic acid solution prepared in the step 1), stirring and dissolving, and carrying out secondary reaction for 2-4 h;
3) Adding an anticoagulant containing carboxyl into the solution obtained in the step 2), and carrying out grafting reaction for 12-48 hours to obtain the grafted aromatic hydrophobic polymer.
2. The hollow fiber membrane according to claim 1, wherein the aromatic dianhydride of step 1) is selected from any one of 3,3',4, 4' -benzophenone tetracarboxylic dianhydride, 4, 4' -hexafluoroisopropylidene-phthalic anhydride, 3',4, 4' -biphenyl tetracarboxylic dianhydride, 1, 2',4, 5' -pyromellitic anhydride, 3',4, 4' -diphenylsulfone tetracarboxylic dianhydride or phthalic anhydride.
3. The hollow fiber membrane according to claim 1, wherein the aromatic diamine of step 1) is selected from any one of 3,3' -dimethyl-4, 4' -diphenyl methane diamine, 4, 4' -diaminodiphenyl methane, 4, 4' -diphenyl methane diisocyanate, 4, 4' -diaminodiphenyl ether and p-phenylenediamine.
4. A hollow fiber membrane according to claim 2 or 3, characterized in that the molar ratio of aromatic dianhydride to aromatic diamine is: (1-1.05): 1.
5. the hollow fiber membrane of claim 1, wherein the polyamine of step 2) is selected from one or more of ethylenediamine, propylenediamine, tris (2-aminoethyl) amine, and quaternium.
6. The hollow fiber membrane according to claim 2 or 5, wherein the molar ratio of the polyamine to the aromatic dianhydride is (2 to 2.05): 1.
7. the hollow fiber membrane according to claim 1, wherein the organic solvent in step 1) is selected from at least one of dimethyl sulfoxide, N-methyl-2-pyrrolidone, N-dimethylformamide, and N, N-dimethylacetamide; and/or
The anticoagulant containing carboxyl groups is selected from heparin or heparin analogues.
8. The hollow fiber membrane according to claim 1, wherein the preparation method of the hollow fiber membrane comprises the steps of: stirring and dissolving polysulfone/polyether sulfone, grafted aromatic hydrophobic polymer, water-soluble pore-forming agent and spinning solution solvent at 80-180 ℃, centrifugally filtering, standing at 40-80 ℃ for 2-24 hours to defoam to obtain spinning solution, and carrying out dry spinning or wet spinning, washing, stretching and drying on the spinning solution to obtain the modified hollow fiber membrane.
9. The hollow fiber membrane according to claim 8, wherein the mass ratio of each component in the spinning solution is: 20-60 parts of polysulfone/polyether sulfone, 20-40 parts of grafted aromatic hydrophobic polymer, 0.1-10 parts of water-soluble pore-forming agent and 100-300 parts of spinning solution solvent.
10. Use of a hollow fiber membrane according to any one of claims 1 to 9 with good biocompatibility for the preparation of a blood purification material.
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