DK163482B - PROCEDURE FOR PREPARING A HYDROPHILIC POLYETHER-POLYCARBONATE MEMBRANE - Google Patents
PROCEDURE FOR PREPARING A HYDROPHILIC POLYETHER-POLYCARBONATE MEMBRANE Download PDFInfo
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- DK163482B DK163482B DK096275A DK96275A DK163482B DK 163482 B DK163482 B DK 163482B DK 096275 A DK096275 A DK 096275A DK 96275 A DK96275 A DK 96275A DK 163482 B DK163482 B DK 163482B
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- Prior art keywords
- membrane
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- membranes
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- 239000012528 membrane Substances 0.000 title claims description 157
- 239000004417 polycarbonate Substances 0.000 title claims description 59
- 229920000515 polycarbonate Polymers 0.000 title claims description 59
- 238000000034 method Methods 0.000 title claims description 31
- 238000001631 haemodialysis Methods 0.000 claims description 30
- 230000000322 hemodialysis Effects 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
- 239000002904 solvent Substances 0.000 claims description 20
- 238000005266 casting Methods 0.000 claims description 19
- 229920001400 block copolymer Polymers 0.000 claims description 18
- 230000008569 process Effects 0.000 claims description 18
- 239000004721 Polyphenylene oxide Substances 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 230000008961 swelling Effects 0.000 claims description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 14
- 229920000570 polyether Polymers 0.000 claims description 14
- 229920001223 polyethylene glycol Polymers 0.000 claims description 14
- IISBACLAFKSPIT-UHFFFAOYSA-N Bisphenol A Natural products C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 IISBACLAFKSPIT-UHFFFAOYSA-N 0.000 claims description 13
- 238000000465 moulding Methods 0.000 claims description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 229920001577 copolymer Polymers 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 239000006184 cosolvent Substances 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 3
- 239000000758 substrate Substances 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 2
- 229920001281 polyalkylene Polymers 0.000 claims description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 claims 1
- 239000002954 polymerization reaction product Substances 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 230000035699 permeability Effects 0.000 description 22
- 239000000243 solution Substances 0.000 description 18
- 239000000463 material Substances 0.000 description 15
- 238000000108 ultra-filtration Methods 0.000 description 14
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 230000004888 barrier function Effects 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000000502 dialysis Methods 0.000 description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- -1 bisphenol A carbonates Chemical class 0.000 description 4
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 4
- 239000012778 molding material Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229960002668 sodium chloride Drugs 0.000 description 3
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 206010018910 Haemolysis Diseases 0.000 description 2
- 229920001202 Inulin Polymers 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000009749 continuous casting Methods 0.000 description 2
- 229940109239 creatinine Drugs 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 238000010612 desalination reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000008588 hemolysis Effects 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 2
- 229940029339 inulin Drugs 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229940045136 urea Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- 125000006091 1,3-dioxolane group Chemical group 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920000298 Cellophane Polymers 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000003939 Membrane transport proteins Human genes 0.000 description 1
- 108090000301 Membrane transport proteins Proteins 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000010425 asbestos Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229930188620 butyrolactone Natural products 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000012045 crude solution Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 238000005530 etching Methods 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000003754 machining Methods 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 230000008384 membrane barrier Effects 0.000 description 1
- 230000009061 membrane transport Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920006380 polyphenylene oxide Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 229910052895 riebeckite Inorganic materials 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 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
- B01D71/50—Polycarbonates
-
- 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
- B01D67/0009—Organic membrane manufacture by phase separation, sol-gel transition, evaporation or solvent quenching
- B01D67/0011—Casting solutions therefor
Landscapes
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Manufacturing & Machinery (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- External Artificial Organs (AREA)
- Manufacture Of Porous Articles, And Recovery And Treatment Of Waste Products (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Polyesters Or Polycarbonates (AREA)
Description
DK 163482BDK 163482B
iin
Den foreliggende opfindelse angår en fremgangsmåde til fremstilling af en hydrofil polyether-polycarbonatmembran til brug ved hæmodialyse, ved hvilken man anvender faseomdannelsesteknik.The present invention relates to a process for the preparation of a hydrophilic polyether polycarbonate membrane for use in hemodialysis using phase conversion technique.
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Fra beskrivelsen til dansk patentansøgning nr. 3613/72 kendes membraner fremstillet af polyphenylenoxid, hvilke membraner i tykkelse varierer fra 50 til 500 micron svarende til fra 2 til 20 mils. Membranernes porer har meget stor diameter, og mem-10 branerne tilbageholder derfor kun stoffer med en molekylvægt på mere end ca. 70.000. De således kendte membraner egner sig derfor ikke til dialyse.From the specification of Danish patent application No. 3613/72, membranes made of polyphenylene oxide are known, which membranes in thickness range from 50 to 500 microns corresponding to from 2 to 20 mils. The pores of the membranes have a very large diameter and therefore the membranes retain only substances with a molecular weight of more than approx. 70,000. The membranes thus known are therefore not suitable for dialysis.
Fra beskrivelsen til dansk patentansøgning nr. 1579/73 kendes 15 en fremgangsmåde til fremstilling af ultra- og hyperfiltre-ringsmembraner af ethylcellulose, hvilke membraner tillader passage af forbindelser med en molekylvægt på op til 20.000 og helt eller delvis tilbageholder forbindelser med en molekylvægt over 20.000. De således kendte membraner kan anvendes til 20 koncentrering af opløsninger og til separering af opløsninger i forskellige fraktioner.From the specification of Danish Patent Application No. 1579/73, there is known a process for the preparation of ultra- and hyperfiltration membranes of ethyl cellulose, which membranes allow passage of compounds having a molecular weight of up to 20,000 and fully or partially retaining compounds having a molecular weight above 20,000. . The membranes thus known can be used for concentrating solutions and for separating solutions into different fractions.
Endvidere kendes fra U.S.A. patentskrift nr. 3.133.132 en fremgangsmåde til fremstilling af en porøs membran, der er be-25 regnet til separering af opløste stoffer fra en opløsning.Also known from U.S.A. U.S. Pat. No. 3,133,132 discloses a process for the preparation of a porous membrane which is intended for the separation of solutes from a solution.
Nærmere betegnet angår patentskriftet fremstilling af en cel-luloseestermembran, som er beregnet til afsaltning af saltvand .More particularly, the patent relates to the preparation of a cellulose ester membrane which is intended for desalination of saline.
30 Fremdeles kendes fra U.S.A. patentskrift nr. 3.3322.894 en fremgangsmåde til fremstilling af en polyviny1encarbonatmem-bran, der er anvendelig til udførelse af omvendt osmose og herunder afsaltning af saltvand.30 Still known from U.S.A. U.S. Patent No. 3,3322,894 discloses a process for producing a polyvinyl carbonate membrane useful for performing reverse osmosis and including desalination of saline.
35 Ingen af de fra ovennævnte litteratursteder kendte membraner kan imidlertid betegnes som en aromat isk-alifat i sk polycarbo-natmembran, der er dannet af en hydrofil polycarbonatcopoly-mer, og ingen af membranerne er en hæmodialysemembran.However, none of the membranes known from the above literature sites can be described as an aromatic isic aliphate in so-called polycarbonate membrane formed from a hydrophilic polycarbonate copolymer, and none of the membranes is a hemodialysis membrane.
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2 Hæmodialysemembraner til anvendelse i den kunstige nyre fremstilles for tiden generelt af cellofanmaterialer. Det bedste af disse for tiden til rådighed stående materialer til dette formål har vist sig at være en cellulose, der er regenereret 5 fra en cuproammoniumopløsning, blødgjort med glycerol og kendes under varemærket "Cuprophan". Selv om "Cuprophan"®-mem-braner tilvejebringer ultrafiltreringshastigheder og clearance af opløste stoffer med lav molekylvægt indenfor de ønskelige intervaller for god hæmodialyse, er de stadig behæftet med 10 mange mangler, som hindrer dem i at være helt tilfredsstillende som hæmodialysemembraner. Visse toksiner, som det antages at være nødvendigt at fjerne fra blodet ved hjælp af hæmodialyse, er "middelmolekyler", dvs. molekyler med molekylvægte i området fra 300 til 5.000. Sådanne middelmolekyler passerer 15 gennem "Cuprophan"®-membraner med hastigheder, der er meget mindre end ønskeligt. Endvidere er brudstyrken og rivestyrken for Cuprophan-membraner mindre end ønskeligt for materialer, der benyttes til hæmodialyse, og deres holdetid er lav, tilsyneladende som følge af vandring af blødgøringsmiddel under 20 lagring. Endvidere har permeabi1 i teten af Cuprophan-membraner-ne vist sig at variere fra parti til parti samt at formindskes ved ældning. Endelig er det meget vanskeligt at frembringe adhæsion mellem Cuprophan og andre materialer og mellem Cuprophan og sig selv. Det er således vanskeligt at benytte forbed-25 rede hæmodialysekonstruktioner, som kræver læksikre rum, hvilket beror på membranmaterialet til afspærring af blod fra dia-lysatopløsning og blod og dialysatopløsninger fra atmosfæren.2 Hemodialysis membranes for use in the artificial kidney are currently generally made of cellophane materials. The best of these currently available materials for this purpose has been found to be a cellulose regenerated from a cuproammonium solution, softened with glycerol and known under the trademark "Cuprophan". Although "Cuprophan" ® membranes provide ultrafiltration rates and clearance of low molecular weight solvents within the desirable intervals for good hemodialysis, they still suffer from 10 many deficiencies that prevent them from being completely satisfactory as hemodialysis membranes. Certain toxins that it is thought necessary to remove from the blood by hemodialysis are "intermediate molecules", ie. molecules with molecular weights ranging from 300 to 5,000. Such intermediate molecules pass 15 through "Cuprophan" ® membranes at rates much less than desirable. Furthermore, the breaking and tearing strength of Cuprophan membranes is less than desirable for materials used for hemodialysis and their holding time is low, apparently due to migration of plasticizer during storage. Furthermore, permeability in the density of Cuprophan membranes has been found to vary from batch to batch and to decrease with aging. Finally, it is very difficult to produce adhesion between Cuprophan and other materials and between Cuprophan and itself. Thus, it is difficult to use improved hemodialysis constructs which require leak-proof spaces, which depend on the membrane material for blocking blood from dialysate solution and blood and dialysate solutions from the atmosphere.
Ved forsøg på udvikling af hæmodialysemembraner med mekaniske 30 egenskaber og transportegenskaber, der er overlegne i forhold til Cuprophans egenskaber, har det tidligere været foreslået at fremstille membraner af polyether-polycarbonat-blokcopolyme-re indeholdende en restmængde hydrofobe, aromatiske polycar-bonatblokke, der bibringer sejhed, og hydrofile polyether-35 blokke, som bibringer permeabilitet for vand og opløste stoffer. Polycarbonatsystemet blev valgt til udvikling af dialysemembraner som følge af de fremragende mekaniske egenskaber,In attempts to develop hemodialysis membranes with mechanical properties and transport properties superior to Cuprophan's properties, it has previously been proposed to prepare membranes of polyether-polycarbonate block copolymers containing a residual amount of hydrophobic, aromatic polycarbonate blocks which toughness, and hydrophilic polyether-35 blocks which impart permeability to water and solutes. The polycarbonate system was chosen for the development of dialysis membranes due to the excellent mechanical properties,
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3 som i handelen gående polycarbonat udviser, den meget lave thrombogenic itet, som korrekt hepariniserede polycarbonatover-flader udviser, letheden ved formning af denne polymertype til forskellige former, såsom film og fibre, og de mange syntetis-5 ke muligheder for kemisk modifikation af det grundlæggende a-romatiske polycarbonatgrundskelet med henblik på opnåelse af ønskede membrantransportegenskaber. Som omtalt i "Proceedings of the 5th Annual Contractors' Conference of the Artificial Kidney Program of the National Institute of Arthritis and Me-10 tabolic Diseases", U.S. Department of Health, Education and Welfare (1972), side 32-33, blev gelatinerede membraner fremstillet ud fra polyether-polycarbonat-blokcopolymere ved hjælp af en faseomfannelsesteknik, dvs. støbning af en opløsning af copolymeren i et passende opløsningsmiddel på en underlags-15 overflade til dannelse af et lag, som kun delvis får lov til at tørre, og som derpå dyppes i et flydende gelatineringsme-dium, i hvilket copolymeren er uopløselig, men som er blandbart med opløsningsmidlet, under anvendelse af chloroform som støbeopløsningsmidlet, og methanol som galatineringsmediet. De 2Q gelatinerede membraner, som resulterer af en sådan procedure, viste sig imidlertid, selv om de viser sig betydelig bedre end Cuprohhan-membraner i henseende til deres permeabilitet for opløste stoffer i middelmolekylområdet, at være behæftet med flere ulemper ved deres praktiske anvendelse som hæmolysemem-25 braner. Først af alt var deres ultrafiltreringshastigheder 2 til 5 gange så store som for "Cuprohan"®-membraner, hvilket ville være klinisk uacceptabelt for hæmodialyse, som den i øjeblikket udføres, på grund af muligheden for at afvanding af patienten finder sted under behandlingen. For det andet var 30 deres brudstyrke ikke større og i mange tilfælde mindre end brudstyrken af "Cuprophan"®-membraner. For det tredie indebar forsøg på kontinuerlig støbning af membranen på maskineri af produktionstypen i bredder, der er passende til anvendelse i kommercielle hæmodialysatorer, yderligere problemer, som gjor-35 de methanol gelatiner ingsproceduren uigennemførlig til kommerciel hæmod i a 1ysemembranfremst i 11 i ng.3, which exhibits commercially available polycarbonate, the very low thrombogenicity exhibiting properly heparinized polycarbonate surfaces, the ease of molding this polymer type into various forms, such as films and fibers, and the many synthetic options for chemical modification thereof. basic α-aromatic polycarbonate backbone to obtain desired membrane transport properties. As discussed in "Proceedings of the 5th Annual Contractors' Conference of the Artificial Kidney Program of the National Institute of Arthritis and Me-10 Tabolic Diseases", U.S. Department of Health, Education and Welfare (1972), pages 32-33, gelatinous membranes were prepared from polyether-polycarbonate block copolymers using a phase conversion technique, i.e. casting a solution of the copolymer in a suitable solvent on a substrate surface to form a layer which is only partially allowed to dry and which is then dipped in a liquid gelatin medium in which the copolymer is insoluble but which is miscible with the solvent, using chloroform as the casting solvent, and methanol as the galating medium. However, the 2Q gelatinous membranes resulting from such a procedure, although significantly better than Cuprohhan membranes in terms of their permeability to solute in the medium molecule region, were found to have several drawbacks in their practical use as a hemolysis chemistries. -25 fires. First of all, their ultrafiltration rates were 2 to 5 times as high as for "Cuprohan" ® membranes, which would be clinically unacceptable for hemodialysis as it is currently performed, due to the possibility of dewatering of the patient during treatment. Second, their breaking strength was not greater and in many cases less than the breaking strength of "Cuprophan" ® membranes. Third, attempts at continuous casting of the membrane on production-type machinery in widths suitable for use in commercial hemodialysers posed additional problems which rendered the methanol gelatinization procedure unfeasible for commercial hemodialysis in aisle membrane production at 11 in ng.
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Det mest alvorlige problem, man stødte på, var den hyppige forekomst af kraftig gennemsivning af albumin gennem membranerne under ultrafiltreringsforsøg, hvilken gennemsivning viste sig at skyldes huller eller andre defekter i den ultratynde 5 overflade af membranen, der danner barrieren mellem blodet og dialysatet eller den strømmende opløsning. Alle disse membraner omtales som værende "anisotope" eller "skinned", hvilket betyder, at deres to sider er betydeligt forskellige fra hinanden, idet den ene side er relativt glat, og den anden side 10 er relativt ru og porøs. Den glatte side er "spærre"-1 åget, som vender mod blodet under hæmolyse og er ganske tynd, dvs. af størrelsesordenen 0,05 til 0,2 micron. Det øvrige af membranen fungerer blot som en understøtning og er ca. 25 til ca.The most serious problem encountered was the frequent occurrence of vigorous permeation of albumin through the membranes during ultrafiltration experiments, which was found to be due to gaps or other defects in the ultrathin surface of the membrane forming the barrier between the blood and dialysate or the flowing solution. All of these membranes are referred to as being "anisotope" or "skinned", meaning that their two sides are significantly different from one another, with one side being relatively smooth and the other side 10 being relatively rough and porous. The smooth side is the "barrier" -1 yoke, which faces the blood during hemolysis and is quite thin, ie. of the order of 0.05 to 0.2 micron. The rest of the membrane simply acts as a support and is approx. 25 to approx.
30 micron tykt. Ubeskadtheden af spærrelaget er afgørende for 15 funktionen af membranen under dialyse. En hvilken som helst perforering, punktur eller andet indgreb på spærrelagets integritet ødelægger brugbarheden af membranen, og alle materialer, der er i kontakt med membranen, siver blot igennem. Det har nu vist sig ved hjælp af elektronmikroskopi, at de metha-20 nol-gelatinerede polycarbonatmembraner dannes med deres spærrelag på den side af membranen, som er i kontakt med den støbende overflade, i stedet for den side af membranen, der vender mod luften under tørring. Betydningen af dette faktum er, at kontinuerlig støbning af disse membraner på maskineri af 25 produktionstypen involverer kontinuerlig afskrælning af det fine spærrelag fra den støbende overfalde under processen, hvilket gør det næsten umuligt at bevare spærrelagets integritet og at opnå en membran, der er egnet til anvendelse ved hæ-modialyse. Det viste sig endvidere, at lang tids udsætning af 30 membranen for methanol påvirker membranegenskaberne, hvilket derved nødvendiggør hurtig og omfattende skylning eller vask-ning af membranen til fjernelse af methanolen derfra og erstatte den med vand med henblik på at give membranen en passende holdetid. Et yderligere problem, som viste sig, var u-35 gennemførligheden af at benytte store voluminer methanol som gelatineringsmediet som følge af udgiften til og toksiciteten og antændeligheden af dette materiale.30 microns thick. The integrity of the barrier layer is essential for the function of the membrane during dialysis. Any perforation, puncture, or other interference with the integrity of the barrier layer destroys the usefulness of the membrane and all materials in contact with the membrane simply seep through. It has now been found by electron microscopy that the methanol-gelatinized polycarbonate membranes are formed with their barrier layers on the side of the membrane which contacts the molding surface, instead of the side facing the air membrane. during drying. The importance of this fact is that continuous casting of these membranes on production-type machinery involves continuous peeling of the fine barrier layer from the casting surface during the process, making it almost impossible to maintain the integrity of the barrier layer and to obtain a membrane suitable for use in hemodialysis. It was further found that prolonged exposure of the membrane to methanol affects the membrane properties, thus necessitating rapid and extensive rinsing or washing of the membrane to remove the methanol therefrom and replace it with water to give the membrane an adequate holding time. A further problem which appeared was the feasibility of using large volumes of methanol as the gelatinizing medium due to the expense and toxicity and flammability of this material.
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Den foreliggende opfindelse tager derfor sigte på fremstilling af hæmodialysemembraner med forbedret permeabilitet overfor opløste stoffer i middelmolekyle-området sammenlignet med de for tiden til rådighed stående hæmodialysemembraner, samtidig 5 med bevarelse af klinisk acceptable ultrafiltreringshastigheder samt klinisk acceptabel clearance af opløste stoffer med lav molekylvægt.Therefore, the present invention is directed to the preparation of hemodialysis membranes with improved permeability to solutes in the intermediate molecule range as compared to currently available hemodialysis membranes, while maintaining clinically acceptable ultrafiltration rates and clinically acceptable low molecular weight solutes.
Et andet sigte med opfindelsen er at opnå hæmodialysemembraner 10 med forbedret brudstyrke og rivestyrke sammenlignet med de for tiden til rådighed stående hæmodialysemembraner.Another object of the invention is to obtain hemodialysis membranes 10 with improved fracture strength and tear strength as compared to currently available hemodialysis membranes.
Et yderligere formål med opfindelsen er at tilvejebringe hæmodialysemembraner med forbedret holdetid sammenlignet med de 15 hæmodialysemembraner, som for tiden står til rådighed. Yderligere er det et sigte med den foreliggende opfindelse at opnå hæmodialysemembraner med forbedret forseg1e1 ighed i forhold til de nuværende hæmodialysemembraner med henblik på at muliggøre læksikre hæmodialysatorrum ved hjælp af simpel varmefor-20 segling af membranerne.A further object of the invention is to provide hemodialysis membranes with improved holding time compared to the 15 hemodialysis membranes currently available. Further, it is an object of the present invention to provide hemodialysis membranes with improved sealability over the current hemodialysis membranes to enable leak-proof hemodialyzer compartments by simple heat sealing of the membranes.
Dette opnås ved hjælp af en fremgangsmåde af den indledningsvis omtalte art, som er ejendommelig ved, at man på overfladen af et underlag med en glat finish støber et lag støbeopløsning 25 med en viskositet i intervallet fra ca. 5 til ca. 30 Pa.s omfattende en polyether-polycarbonat-blokcopolymer, som består af 5-35 vægt% gentagende polyalkylenethercarbonatenheder og fra 95 til ca. 65 vægtdele gentagende bisphenol A-carbonaten-heder, og som har en molekylvægt på 50.000 til ca. 750.000 30 bestemt ved måling af det logaritmiske viskositetstal, og et med vand blandbart organisk opløsningsmiddel sammen med et co-opløsningsmiddel, der fungerer som kvældemiddel for copolyme-ren, tørrer nævnte lag til delvis fordampning af opløsningsmidlerne derfra, neddykker det delvis tørrede lag i vand til 35 dannelse af en geleret membran og fjerner den gelerede membran fra underlagets overflade.This is achieved by a method of the kind mentioned in the preamble, which is characterized in that a layer of casting solution 25 having a viscosity in the range of approx. 5 to approx. 30 Pa.s comprising a polyether polycarbonate block copolymer consisting of 5-35 wt% repeating polyalkylene ether carbonate units and from 95 to about 65 parts by weight of repeating bisphenol A carbonates and having a molecular weight of 50,000 to approx. 750,000 determined by measuring the logarithmic viscosity number and a water-miscible organic solvent together with a co-solvent acting as a swelling agent for the copolymer dries said layer to partially evaporate the solvents therefrom, immerses the partially dried layer in water to form a gelled membrane and remove the gelled membrane from the surface of the substrate.
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Ved anvendelse i et hæmodialyseapparat har den ved fremgangsmåden ifølge opfindelsen fremstillede membran egenskaber til fortrinsvis at fjerne molekyler med middelstor molekylvægt fra blod.When used in a hemodialysis apparatus, the membrane prepared by the method of the invention preferably has the ability to remove molecules of medium molecular weight from blood.
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Membranen fremstillet ved fremgangsmåden ifølge opfindelsen er betydelig bedre end membranerne fremstillet af de hidtil kendte materialer, f.eks. "Cuprophan"®, på følgende områder.The membrane produced by the method of the invention is significantly better than the membranes made from the known materials, e.g. "Cuprophan" ®, in the following areas.
10 1. Polycarbonatmembraner muliggør en clearance af vigtige "middelmolekyler”, der er indtil tre gange større end muligt med nCuprophan"®-membranen ved sammenligningsforsøg.10 1. Polycarbonate membranes allow for clearance of important "intermediate molecules" that are up to three times larger than possible with the nCuprophan® membrane in comparison experiments.
2. Brudstyrken af polycarbonatmembraner er 1% - 2 gange så 15 stor som brudstyrken af ,,Cuprophan"®-membraner.2. The breaking strength of polycarbonate membranes is 1% - 2 times as great as the breaking strength of ,, Cuprophan "® membranes.
3. Bredden af membranegenskaber, som kan opnås med polycarbo-nater, er betydelig og kan indrettes efter behov som ønsket.3. The width of membrane properties obtainable with polycarbonates is considerable and can be adjusted as required.
20 4. Polycarbonatmembraner er stivere end "Cuprophan"®-membraner i våd tilstand. Denne egenskab resulterer i tyndere blodlag i dialysatorer, mere effektiv dialyse og mindre blod-priming vo-1 umen.4. Polycarbonate membranes are stiffer than "Cuprophan" ® membranes in the wet state. This property results in thinner blood layers in dialyzers, more efficient dialysis and less blood-priming volume.
25 5. Polycarbonater er varmeforseglel ige i våd eller tør til stand, hvilket muliggør en stor bredde i dialysatorudform-ni ngen.5. Polycarbonates are heat-sealable in wet or dry condition, which allows for a wide width in the dialyzer design.
6. Som følge af polycarbonatmembraners større dialyseeffekti-30 vitet fås en væsentlig forkortet dialysetid (9 timer/uge) sammenlignet med "Cuprophan"®-membraner.6. Due to the greater dialysis efficiency of polycarbonate membranes, a significantly shorter dialysis time (9 hours / week) is obtained compared to "Cuprophan" ® membranes.
I en udførelsesform for fremgangsmåden ifølge opfindelsen har polymeren en molekylvægt i intervallet fra 200.000 til 500.000 35 bestemt ved måling af det logaritmiske viskositetstal. Herved opnås ultrafiltreringshastigheder, som er klinisk acceptable til anvendelse ved hæmodialyse.In one embodiment of the process of the invention, the polymer has a molecular weight in the range of 200,000 to 500,000 determined by measuring the logarithmic viscosity number. Hereby ultrafiltration rates are obtained which are clinically acceptable for use in hemodialysis.
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Fremgangsmåden ifølge opfindelsen er let og økonomisk at tilpasse til maskinprodukt ion i stor skala uden svækkelse af u-skadtheden af membranens spærrelag.The method of the invention is easily and economically adaptable to large scale machine product ion without attenuating the inertia of the membrane barrier layer.
5 Dette opnås ifølge opfindelsen ved fremstilling af en gelatineret polycarbonatmembran udfra en polyether-polycarbonat-blokcopolymer ved hjælp af den faseomdannelsesteknik, som anvender et vandigt gelatineringssystem med vand som gelatineringsmedium og et med vand blandbart organisk opløsningsmiddel 10 som støbeopløsningsmiddel.This is achieved according to the invention by preparing a gelatinous polycarbonate membrane from a polyether-polycarbonate block copolymer by the phase conversion technique which uses an aqueous gelatinization system as a gelatinizing medium and a water miscible organic solvent 10 as a casting solvent.
Det har vist sig, at gelantinerede polycarbonatmembraner fremstillet på denne måde med vand som det geldannende medium formes med deres spærrelag på den side af membranen, som vender 15 mod luften under tørring, i stedet for på den side af membranen, som er i kontakt med støbeoverfladen, således som det er tilfældet for methanolgelatinerede polycarbonatmembraner, hvilket gør det muligt for den gelatinerede membran let at blive fjernet fra støbeoverfladen uden forringelse af uskadtheden af 20 det fine spærrelag, hvorved maskinprodukt ion i stor skala af sådanne membraner gøres praktisk gennemførlig. Anvendelsen af vand som geldannende medium i stedet for methanol letter også mask i nprodukt i on i stor skåle, som følge af at vand selvsagt er mindre dyrt, ikke-toksisk og uantændeligt, og brugen af 25 vand eliminerer også nødvendigheden af omfattende skylning eller vaskning af membranen med henblik på fjernelse af det geldannende medium derfra, således som det var krævet ved metha-nolgelatinering. Det har også vist sig, at de vand-gelatinere-de polycarbonatmembraner har en betydelig højere styrke end 30 både methanolgelatinerede polycarbonatmembraner og de metha- nolgelatinerede "Cuprophan"®-membraner. Gelatinerede polycarbonatmembraner fremstillet ifølge den foreliggende opfindelse har endvidere vist sig at være betydelig overlegne i forhold til "Cuprophan"®-membraner i henseende til deres permeabi1 ite-35 ter overfor opløste stoffer i middel-molekylområdet, medens ultrafiltreringshastigheder og celarance af opløste stoffer med lav molekylvægt bevares sammenlignet med hvad der er til-It has been found that gelatinous polycarbonate membranes made in this way with water as the gelling medium are formed with their barrier layers on the side of the membrane facing the air during drying, rather than on the side of the membrane which is in contact with the the molding surface, as is the case for methanol-gelatinous polycarbonate membranes, which allows the gelatinized membrane to be easily removed from the molding surface without impairing the innocence of the fine barrier layer, thus making machine-scale large-scale production of such membranes practically feasible. The use of water as a gelling medium in place of methanol also facilitates masking in large-scale on-product products, as water is obviously less expensive, non-toxic and non-flammable, and the use of 25 water also eliminates the need for extensive rinsing or washing. of the membrane for removal of the gelling medium therefrom, as required by methanol gelatinization. It has also been found that the water-gelatinized polycarbonate membranes have a significantly higher strength than both methanol-gelatinized polycarbonate membranes and the methanol-gelatinized "Cuprophan" ® membranes. Furthermore, gelatinous polycarbonate membranes made in accordance with the present invention have been found to be significantly superior to "Cuprophan" ® membranes with respect to their permeability to intermediate molecular region solutes, while ultrafiltration rates and low solubility solvents. molecular weight is retained compared to what is
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8 fældet for "Cuprophan"®-membraner. Det har endvidere vist sig, at ultrafiItreringshatighederne for membranerne fremstillet ifølge den foreliggende opfindelse kan styres til niveauer, som ved hjælp af korrekt valg af molekylvægten af polyether-5 polycarbonat-blokcopolymeren, der benyttes til fremstilling af membranen, kan sammenlignes med ultrafiltreringshastighederne for "Cuprophan"®-membraner.8 precipitated for "Cuprophan" ® membranes. Furthermore, it has been found that the ultrafiltration rates of the membranes made in accordance with the present invention can be controlled to levels comparable to the ultrafiltration rates of "Cuprophan by means of proper selection of the molecular weight of the polyether-polycarbonate block copolymer used to prepare the membrane. "® membranes.
Polycarbonatmaterialet, af hvilket de forbedrede hæmodialyse-10 membraner fremstilles ifølge den foreliggende opfindelse, er en polyetherpolycarbonat-blokcopolymer, som indeholder fra ca.The polycarbonate material from which the improved hemodialysis membranes are prepared in accordance with the present invention is a polyether polycarbonate block copolymer containing from ca.
5 til ca. 35 vægt% af polyetherkomponenten. Det har vist sig, at denne mængde polyetherblokke gør det normalt hydrofobe po-lycarbonat tilstrækkelig hydrofilt til at gøre det egnet til 15 anvendelse som en hæmodialysemembran. Sådanne blokcopolymere kan f.eks. fremstilles ved hjælp af fremgangsmåden ifølge Goldberg (Journal of Polymer Science; Part C, nr. 4, side 707-730 [1963]), ved hvilken en comonomerblanding af fra ca.5 to approx. 35% by weight of the polyether component. It has been found that this amount of polyether blocks makes the normally hydrophobic polycarbonate sufficiently hydrophilic to make it suitable for use as a hemodialysis membrane. Such block copolymers can e.g. is prepared by the method of Goldberg (Journal of Polymer Science; Part C, No. 4, pages 707-730 [1963]), in which a comonomer mixture of from ca.
95 til ca. 65 vægt% 2,2-(4,4'-dihydroxydiphenyl)propan, der 20 generelt kendes som bisphenol A, og tilsvarende fra ca. 5 til ca. 35 vægt% af en polyetherglycol, såsom polyethylenglycol, omsættes med et carboxylsyrederivat, såsom phosgen. En polyethylenglycol, der har vist sig at være særlig egnet, er "Carbowax®6000", som er en polyethylenglycol med en gennem-25 snitlig molekylvægt på 6700, selv om polyethylenglycoler med andre molekylvægte også kan benyttes, såsom eksempelvis "Car-bowax®600", "Carbowax®1000" og "Carbowax®4000", som er polyethylenglycoler med molekylvægte på henholdsvis 600, 1000 og 4000. Polyetherglycoler ud over polyethylenglycoler kan også 30 benyttes, såsom eksempelvis polypropylenoxid-polyethylenoxid-blokcopolymere, der er eksemplificeret ved repræsentanter fra "Pluronic"®-diolserien, såsom "F1uronic®F68".95 to approx. 65% by weight of 2,2- (4,4'-dihydroxydiphenyl) propane, which is generally known as bisphenol A, and correspondingly from ca. 5 to approx. 35% by weight of a polyether glycol such as polyethylene glycol is reacted with a carboxylic acid derivative such as phosgene. A polyethylene glycol which has been found to be particularly suitable is "Carbowax®6000", which is a polyethylene glycol having an average molecular weight of 6700, although polyethylene glycols of other molecular weights may also be used, such as, for example, "Carbowax® 600 "," Carbowax® 1000 "and" Carbowax® 4000 "which are polyethylene glycols having molecular weights of 600, 1000 and 4000 respectively. Polyether glycols in addition to polyethylene glycols may also be used, such as, for example, polypropylene oxide-polyethylene oxide block copolymers exemplified by representatives from the "Pluronic" ® diol series, such as "F1uronic®F68".
Polyether-polycarbonat-blokcopolymere med molekylvægte gående 35 fra ca. 50.000 til ca. 750.000 kan hens igtsmæsæsigt fremstil les på den ovennævnte måde. Et foretrukket molekylvægtinterval går fra ca. 200.000 til ca. 500.000, eftersom det har vistPolyether polycarbonate block copolymers with molecular weights ranging from about 50,000 to approx. 750,000 can be appropriately prepared in the above manner. A preferred molecular weight range is from approx. 200,000 to approx. 500,000, as it has shown
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9 sig, at membraner fremstillet ifølge den foreliggende opfindelse udfra polyetherpolycarbonat-blokcopolymere med molekylvægte indenfor et sådant foretrukket interval udviser ultrafiltreringshastigheder, som kan sidestilles med "Cuprophan"®-5 membraners ultrafiltreringshastigheder og derfor ligger indenfor det interval, som er klinisk acceptabelt til anvendelse ved hæmodialyse.9, that membranes made in accordance with the present invention from polyether polycarbonate block copolymers with molecular weights within such a preferred range exhibit ultrafiltration rates comparable to "Cuprophan" ® 5 membranes ultrafiltration and therefore are within the range clinically acceptable for use. hemodialysis.
Støbeopløsninger til anvendelse ved fremgangsmåden ifølge den 10 foreliggende opfindelse fremstilles ved opløsning af polyether-polycarbonat-blokcopolymeren i et med vand blandbart organisk opløsningsmiddel for copolymeren. Opløsningsmidlet har fortrinsvis et kogepunkt indenfor intervallet 50 til 85°C med henblik på optimal støbning ved stuetemperatur. Det foretrukne 15 opløsningsmiddel er 1,3-dioxolan, som har en passende kombination af høj opløsningsmiddelkraft for copolymeren, blandbarhed med vand og et kogepunkt på 75-76°C. Andre egnede opløsningsmidler, som kan benyttes, omfatter 1,3-dioxan, 1,4 dioxan, te-trahydrofuran, butyrolacton, acetonitril, cel 1 osol veacetat, 20 dimethyl formamid, pyridin og blandinger deraf. Chloroform, som tidligere har været foreslået til anvendelse som et støbeopløsningsmiddel ved methanol-gelatineringen af polycarbonat-membraner, er ikke egnet, eftersom den ikke er blandbar med vand.Molding solutions for use in the process of the present invention are prepared by dissolving the polyether-polycarbonate block copolymer in a water-miscible organic solvent for the copolymer. The solvent preferably has a boiling point within the range of 50 to 85 ° C for optimum molding at room temperature. The preferred solvent is 1,3-dioxolane, which has a suitable combination of high solvent power for the copolymer, water miscibility and a boiling point of 75-76 ° C. Other suitable solvents which may be employed include 1,3-dioxane, 1,4-dioxane, tetrahydrofuran, butyrolactone, acetonitrile, cell 1 osole acetate, dimethyl formamide, pyridine and mixtures thereof. Chloroform previously proposed for use as a casting solvent in the methanol gelatinization of polycarbonate membranes is not suitable as it is immiscible with water.
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Støbeopløsningerne er generelt sammensat således, at de har et totalt indhold af faste stoffer fra ca. l til 20 vægt% med henblik på frembringelse af doper, som i viskositet går fra ca. 5 til ca. 30 Pa.s. Indholdene af fast stof går typisk fra 30 ca. 10 til ca. 20 vægt% med henblik på frembringelse af viskositeter fra ca. 7 til ca. 25 Pa.s, som er det foretrukne interval. Et kvældemiddel, såsom di methylsu1foxid, sættes fordelagtigt til støbeopløsningen i mængder fra ca. 10 til ca. 75 vægt% af copolymeren, idet det foretrukne interval går fra ca.The casting solutions are generally composed such that they have a total solids content of approx. 1 to 20% by weight for the production of dopes which in viscosity range from approx. 5 to approx. 30 Pa.s. The solids content typically ranges from about 30 approx. 10 to approx. 20% by weight in order to produce viscosities of approx. 7 to approx. 25 Pa.s, which is the preferred range. A swelling agent, such as di methyl sulfoxide, is advantageously added to the molding solution in amounts of from about 10 to approx. 75% by weight of the copolymer, the preferred range being from approx.
35 15 til ca. 25 vægt% af copolymeren. Tilsætningen af kvældemid- let har vist sig at forøge permeabi1 i teten af den resulterende membran. Andre kvældemidler, som har været benyttet, omfatter35 to approx. 25% by weight of the copolymer. The addition of the swelling agent has been shown to increase permeability in the density of the resulting membrane. Other choking agents that have been used include
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10 dimethylformamid, dimethylacetamid, acetami d, formamid og py-r i d i n .10 dimethylformamide, dimethylacetamide, acetamide d, formamide and py-r i d i n.
Fremstillingen af polycarbonatmembranen kan udføres på konti-5 nuerlig måde ved hjælp af en skraber under støbning af støbeopløsningen på en bevægende overflade med en glat overfladefinish, såsom et belagt slippapir. Den godt filtrerede (10 pm) støbeopløsning føres fortrinsvis til en beholder, der er placeret foran skraberen, ved hjælp af en portioneringspumpe med 10 positiv forskydning. Beholderen har endeledeorganer til styring af bredden af membranlaget. Tykkelsen af membranlaget styres ved indstilling af mellemrummet mellem kniven og den bevægende båndoverflade, hvilket mellemrum sædvanligvis indstilles til opnåelse af en endelig membrantykkelse på 25,4 til 15 38,1 x 10_6m.The preparation of the polycarbonate membrane can be carried out in a continuous manner by means of a scraper while casting the molding solution on a moving surface with a smooth surface finish, such as a coated release paper. The well-filtered (10 µm) molding solution is preferably fed to a container located in front of the scraper by means of a 10-part positive displacement pump. The container has end members for controlling the width of the membrane layer. The thickness of the membrane layer is controlled by adjusting the space between the knife and the moving belt surface, which space is usually set to obtain a final membrane thickness of 25.4 to 38.1 x 10_6m.
Den netop støbte og våde hinde får lov til at lufttørre ved temperaturer gående fra ca. 20 til ca. 30°C i et tidsrum, der går fra ca. 1,0 til ca. 5,0 minutter med henblik på delvis 20 fordampning af opløsningsmidlet derfra, idet tørretiden be stemmes af såvel båndhastigheden som tørrestrækningen. Den delvis tørrede hinde gelat i neres til frembri ngelse af den endelige membran ved hjælp af dypning i et vandbad samtidig med at den stadig klæber til det bevægende bånd. Gelatineringsbad-25 temperaturen kan varieres fra ca. 0 til ca. 40°C , idet det foretrukne interval er fra 20 til 30°C . Efter gelatinering skrælles membranen af fra det bevægende bånd og vikles separat fra båndet op på en cylindrisk kerne. Membranen vaskes til slut grundigt med deioniseret vand til fjernelse af de sidste 30 spor af opløsningsmiddel og kvældemiddel og lagres i en lukket plastpose eller en anden beholder indeholdende vand og et steriliserende middel, såsom formaldehyd. Den endelige tykkelse af membranen varierer generelt fra ca. 25,4 til ca. 38,1 x 10-6m, afhængigt af knivgabets indstilling, støbeopløsningen's 35 viskositet og båndhastigheden.The just molded and wet membrane is allowed to air dry at temperatures ranging from approx. 20 to approx. 30 ° C for a period ranging from approx. 1.0 to approx. 5.0 minutes for partial evaporation of the solvent therefrom, the drying time being determined by both the band speed and the drying distance. The partially dried membrane is gelatinized to produce the final membrane by dipping into a water bath while still adhering to the moving band. The gelatin bath temperature can be varied from approx. 0 to approx. 40 ° C, the preferred range being from 20 to 30 ° C. After gelatinization, the membrane is peeled off from the moving band and wound separately from the band onto a cylindrical core. Finally, the membrane is thoroughly washed with deionized water to remove the last 30 traces of solvent and swelling agent and stored in a sealed plastic bag or other container containing water and a sterilizing agent such as formaldehyde. The final thickness of the membrane generally varies from approx. 25.4 to approx. 38.1 x 10-6m, depending on the knife gap setting, the cast solution's viscosity and the tape speed.
Opfindelsen illustreres nærmere i de følgende eksempler.The invention is further illustrated in the following examples.
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Eksempel 1Example 1
En blanding af 491 g af polyether-polycarbonat-blokcopolymeren opnået ved omsætning af phosgen med en comonomerblånding af 5 "bisphenol A" (75 vægt%) og "Carbowax®6000" (25 vægt%), og med et grænseviskositetstal på 1,7 (i chloroform ved 25°C) svarende til en molekylvægt på 377.000, 3146 g 1,3-dioxolan og 98,2 g dimethylsulfoxid blev langsomt omrørt, indtil opløsning fandt sted (ca. 8 timer). Den rå opløsning blev i et trykfil-10 ter ved 3,1 til 4,5 atm filtreret gennem en polypropylenfilt eller gennem 25 μιη porøs asbestpiademedium til fjernelse af en lille rest af fint uopløseligt materiale. Den resulterende støbeopløsning har en viskositet på 16 Pa.s. ved 25°C.A mixture of 491 g of the polyether polycarbonate block copolymer obtained by reaction of phosgene with a comonomer blend of 5 "bisphenol A" (75 wt%) and "Carbowax®6000" (25 wt%), and having an intrinsic viscosity of 1.7 (in chloroform at 25 ° C) corresponding to a molecular weight of 377,000, 3146 g of 1,3-dioxolane and 98.2 g of dimethyl sulfoxide were slowly stirred until dissolution took place (about 8 hours). The crude solution was filtered into a pressure filter at 3.1 to 4.5 atm through a polypropylene felt or through 25 μιη porous asbestos pad medium to remove a small residue of finely insoluble material. The resulting casting solution has a viscosity of 16 Pa.s. at 25 ° C.
15 Ca. 1,9 liter af ovennævnte 10 pm filtrerede støbeopløsning blev via en skraber støbt på overfladen af et 40,6 cm bredt bevægende bånd, som bevægede sig med en hastighed på 71,9 cm pr. min. Beholderens ende-ledeorganer blev indstillet til frembringelse af en støbt hinde med en bredde på 39,4 cm, idet 20 mellemrummet mellem skraberen og den bevægende båndoverflade blev indstillet på 177,8 x 10“6m. Disse dimensioner tilveje-bringer prøver, som er egnede til anvendelse i Ki i 1-dialysatoren. En total tørretid for den støbte hinde på 2,54 min. fik lov at hengå før gelatinering i et vandbad. Den omgivende 25 lufts temperatur blev holdt på 24,7± 0,4°C, og temperaturen af gelatineringsvandbadet blev holdt på 25± 0,5°C. Efter gelatinering blev den resulterende membran trukket af fra det bevægende bånd og separat fra båndet viklet op på en cylindrisk kerne. Ialt 53,95 m membran blev således fremstillet i løbet 30 af et tidsrum på 75 minutter. Membranen blev vasket i en strøm af deioniseret vand og opbevaret i en forseglet polyethylen-pose indeholdende 2% vandig formaldehyd.15 Approx. 1.9 liters of the above 10 µm filtered casting solution were cast via a scraper onto the surface of a 40.6 cm wide moving band moving at a rate of 71.9 cm per mine. The end members of the container were set to produce a molded web of 39.4 cm width, with the gap between the scraper and the moving tape surface being set at 177.8 x 10 6 cm. These dimensions provide samples suitable for use in Ki in the 1-dialyzer. A total drying time of the molded membrane of 2.54 min. were allowed to hang before gelatinizing in a water bath. The ambient 25 air temperature was maintained at 24.7 ± 0.4 ° C and the temperature of the gelatin water bath was maintained at 25 ± 0.5 ° C. After gelatinization, the resulting membrane was detached from the moving band and separately wound from the band onto a cylindrical core. Thus, a total of 53.95 m of membrane was prepared over a period of 75 minutes. The membrane was washed in a stream of deionized water and stored in a sealed polyethylene bag containing 2% aqueous formaldehyde.
Den som ovenfor anført fremstillede polycarbonatmembran viste 35 sig at have fysiske egenskaber og permeabi1 itetsegenskaber som anført i den efterfølgende tabel 1. Med henblik på sammenligning anføres tilsvarende værdier for en typisk prøve afThe polycarbonate membrane prepared as mentioned above was found to have physical and permeability properties as set forth in the following Table 1. For comparison purposes, similar values are given for a typical sample of
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12 "Cuprophan"®PT150 membran. Permeabi1 itetsegenskaberne blev bestemt i en dialyseforsøgscelle af den type, som er udformet af the National Bureau of Standards.12 "Cuprophan" ® PT150 membrane. The permeability properties were determined in a dialysis test cell of the type designed by the National Bureau of Standards.
5 TABEL 1TABLE 1
Polycarbonat- membran ifølge "Cuprophan"®PT _eksempel 1 150 membran Vådtykkelse, m 33 x 10~6 22,9 x 10“6 10Polycarbonate Membrane according to "Cuprophan" ®PT Example 1 150 Membrane Wet Thickness, m 33 x 10 ~ 6 22.9 x 10 "6 10
Relativ brudstyrke, cm Hg 30 20Relative breaking strength, cm Hg 30 20
Ultrafiltreri ngshastighed ved 37°C, 200 mm HgåP, ml/m2- time-mm Hg 3,6 3,9Ultrafiltration rate at 37 ° C, 200 mm HgP, ml / m2 hour-mm Hg 3.6 3.9
Diffusionspermeabilitet ved 15 37eC, cm/min (xlO4) (molekyl vægt af fast stof i parentes) natriumchlorid (58,4) 709 707 vitamin B12 (1355) 101 46 human serumalbumin (60.000) 0 0 20 -Diffusion permeability at 37 ° C, cm / min (x104) (molecular weight of solid in brackets) sodium chloride (58.4) 709 707 vitamin B12 (1355) 101 46 human serum albumin (60,000) 0 0 20 -
Det fremgår af dataene i tabel 1, at polycarbonatmembranen fremstillet ifølge den foreliggende opfindelse, som har ca.It can be seen from the data in Table 1 that the polycarbonate membrane made in accordance with the present invention which has approx.
40% større tykkelse med "Cuprophan"®-membranen og ca. samme ultrafiltreringshastighed og permeabilitet overfor natri um-25 chlorid, som er et opløst stof med en repræsentativ lav molekylvægt i blod, udviser en 50% højere brudstyrke og en 120% højere permeabilitet overfor vitamin Bi2> som er et eksempel på et opløst stof med middelmolekylvægt, medens den er fuldstændig uigennemtrængelig for serumalbumin, der er en kompo-30 nent med høj molekylvægt i blod, hvis fjernelse fra blodet under hæmodialyse ikke er ønskelig.40% greater thickness with the "Cuprophan" ® membrane and approx. the same ultrafiltration rate and permeability to sodium chloride, which is a solute with a representative low molecular weight in blood, exhibits a 50% higher breaking strength and a 120% higher permeability to vitamin Bi2, which is an example of a medium molecular weight solute while completely impermeable to serum albumin, which is a high molecular weight component of blood whose removal from the blood during hemodialysis is not desirable.
Det har yderligere vist sig, at polycarbonatmembranen fremstillet ifølge den foreliggende opfindelse er betydelig sti-35 vere i våd tilstand end "Cuprophan,,®-membraner. Dette er vigtigt ved hæmodialyse i henseende til bevarelse af en tynd blodhinde, et større areal blod til dialyse og et lavt blod-It has further been found that the polycarbonate membrane made in accordance with the present invention is significantly stiffer in wet condition than "Cuprophan" ® membranes. This is important in hemodialysis for preservation of a thin anemia, a larger area of blood. dialysis and a low blood
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13 priming volumen. Polycarbonatmembranen ifølge den foreliggende opfindelse er endvidere varmeforseglelig, hvilket muliggør større bredde i hæmodialysatorudformningen. Endvidere har polycarbonatmembranen ifølge opfindelsen vist sig at være ikke-5 toksisk ved en række in vitro- og dyreforsøg, og at være forligelig med blod, og membranens thrombogenicitet er ca. den samme som for "Cuprophan"®-membraner in vitro.13 priming volume. Furthermore, the polycarbonate membrane of the present invention is heat sealable, which allows for greater width in the hemodialyzer design. Furthermore, the polycarbonate membrane of the invention has been found to be nontoxic in a variety of in vitro and animal experiments, and to be blood compatible, and the thrombogenicity of the membrane is approx. the same as for "Cuprophan" ® membranes in vitro.
Undersøgelse af polycarbonatmenbranen fremstillet ifølge ek-10 sempel 1 under anvendelse af vand som gelatineringsmedium ved hjælp af scanderende elektrofotomikroskopi viste, at den side af membranen, der vendte mod luften under tørring, var glat-tere og mere jævn end den side af membranen, som var i kontakt med støbeoverfladen, hvilket viser, at membranen blev dannet 15 med sit spærrelag eller aktive lag på den side af membranen, der vender mod luften under tørri ngen, i stedet for den side af membranen, som er i kontakt med støbeoverfladen, således som tilfældet er for methanol-gel at inerede polycarbonat-mem-braner. Den kontinuerlige aftrækning af membranen fra den be-20 vægende båndoverflade har således ingen skadelig virkning på membranens fine spærrelag, hvilket gør maskinfremsti 11ing af membranen i stor skala gennemførlig. Den vand-gelatinerede polycarbonatmembran fremstillet ifølge eksempel 1 viste sig også at have en meget finere og mere ensartet ultragelstruktur 25 end en lignende membran fremstillet ved hjælp af methanol gela-tinering. Dette afspejles i den betydelig højere styrke af de vandgel at inerede polycarbonatmembraner, som har vist sig at have brudstyrker, der er 50-70% større end brudstyrkerne for de tilsvarende methanolgelatinerede polycarbonatmembraner.Examination of the polycarbonate membrane produced according to Example 1 using water as a gelatinization medium by scanning electrophotomicroscopy showed that the side of the membrane facing the air during drying was smoother and more smooth than the side of the membrane which was in contact with the mold surface, showing that the membrane was formed with its barrier layer or active layer on the side of the membrane facing the air during the drying, instead of the side of the membrane which contacts the mold surface, thus as is the case for methanol-gel to inert polycarbonate membranes. Thus, the continuous pulling of the membrane from the moving tape surface has no detrimental effect on the fine barrier layer of the membrane, making machine fabrication of the membrane large-scale feasible. The water-gelatinized polycarbonate membrane prepared according to Example 1 was also found to have a much finer and more uniform ultragel structure 25 than a similar membrane made by methanol gelatinization. This is reflected in the significantly higher strength of the water gel inert polycarbonate membranes, which have been found to have fracture strengths 50-70% greater than the fracture strengths of the corresponding methanol gelatinized polycarbonate membranes.
3030
Det vil således fremgå, at fremgangsmåden ifølge opfindelsen muliggør maskinfremsti 11 ing i stor skala af polycarbonat-mem-braner, som er anvendelige til hæmodialyse, og som udviser forbedret styrke og forbedrede permeabi1iteter overfor opløste 35 stoffer i middel-molekylområdet sammenlignet med for tiden til rådighed stående hæmodialysemembraner, samtidig med bevarelse af ultrafiltreringshastigheder indenfor det klinisk acceptableThus, it will be appreciated that the process of the invention enables large-scale machining of polycarbonate membranes useful for hemodialysis, which exhibits improved strength and improved permeabilities to dissolved substances in the average molecular range as compared to available hemodialysis membranes, while maintaining ultrafiltration rates within the clinically acceptable range
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14 interval med hensyn til undgåelse af afvanding og også bevarelse af clearance af opløste stoffer med lav molekylvægt indenfor det klinisk acceptable interval med henblik på undgåelse af lav molekylvægt - udmatte!sessyndrom.14 interval for avoiding dewatering and also maintaining clearance of low molecular weight solutes within the clinically acceptable range for low molecular weight avoidance - fatigue syndrome.
55
Eksempel 2Example 2
Dette eksempel viser effektiviteten af til støbeopløsningsmaterialet tilsat kvældemiddel i henseende til forøgelse af per-10 meabiliteten for vand og opløst stof af polycarbonatmembraner fremstillet ifølge den foreliggende opfindelse.This example demonstrates the effectiveness of swelling agent added to the molding material in increasing the permeability of water and solute of polycarbonate membranes made in accordance with the present invention.
Gelatinerede membraner blev støbt under identiske betingelser ud fra støbematerialer indeholdende en polyether-polycarbonat-15 blokcopolymer opnået ved omsætning af phosgen med en comono-merblanding af "bisphenol A" (75 vægt%) og "Carbowax®6000" (25 vægt%) og med et grænseviskositetstal på 1,2 (i chloroform ved 25eC), svarende til en molvægt på 190.000. Støbeopløsningsmaterialerne indeholdt varierende mængder af kvældemidlet dime-20 thylsulfoxid (DMS0). Egenskaberne af de resulterende polycarbonatmembraner, som funktion af mængden af DMSO-kvæl-demiddel i støbematerialet, er opført i tabel 2. Tilsvarende værdier er til sammenligning anført for en typisk prøve af "Cupro-phan"®PT-150.Gelatinous membranes were cast under identical conditions from molding materials containing a polyether polycarbonate-15 block copolymer obtained by reaction of phosgene with a comonomer mixture of "bisphenol A" (75 wt%) and "Carbowax®6000" (25 wt%) and with an intrinsic viscosity number of 1.2 (in chloroform at 25 ° C), corresponding to a molecular weight of 190,000. The casting materials contained varying amounts of the swelling agent dimethyl sulfoxide (DMSO). The properties of the resulting polycarbonate membranes, as a function of the amount of DMSO nitrogen in the molding material, are listed in Table 2. Corresponding values are given for a typical sample of "Cupro-phan" ®PT-150.
25 30 3525 30 35
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DK 163482 BDK 163482 B
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Dataene i tabel 2 viser tydeligt den udtalte virkning af at sætte DMSO til støbeopløsningen i henseende til graden af membrankvældning målt ved hjælp af membran-vådtykkel se og -vandindhold med resulterende forøgelse af membranpermeabi1i-5 tet overfor vand og forskellige opløste stoffer. Polycarbonat-membranen fremstillet under anvendelse af støbematerialet, der ikke indeholder noget kvældemiddedl, udviste permeabi1 itetse-genskaber, der kan sidestilles med egenskaberne af en typisk "Cuprophan"®PT150-membran. Tilsætning af den første mængde 10 DMSO-kvældemiddel (2 g pr. 15 g polymer) til støbematerialet ses at have næsten fordoblet vandindholdet og tredoblet den hydrauliske permeabilitet (målt ved hjælp af ultrafiltreringshastighed) af membranen samt at have forøget permeabi1 i teten overfor alle de afprøvede opløste stoffer. Graden af permeabi-15 1 itetsforøgelse steg med molekylstørrelsen af opløst stof, idet 24-37% højere værdier blev iagttaget i tilfælde af mindre mængder opløste stoffer, såsom urinstof og creatinin, og en meget tydelig forøgelse på 160% blev fundet for inulin, som er et typisk eksempel på et opløst stof i det øvre "middelmoleky-20 le"-interval. Yderligere stigning af mængden af kvældemiddel i støbematerialet (til 4 g pr. 15 g polymer) ses at have forøget pol yearbonatmembranens vandindhold og vandpermeabi1 i tet yderligere, idet permeabi1 i teten overfor opløste stoffer med mindre molekylvægt kun blev forøget en smule (2-7%) (dvs. natri-25 umchlorid, urinstof, creatinin og urinsyre), medens der stadig skete en væsentlig forøgelse af "middelmolekyle"-permeabi1ite-ten (henholdsvis 22, 24 og 60%'s forøgelse for phosphat, raf-finose og inulin). Betydningsfuldt er det, at polycarbonatmem-branerne fuldstændig afviser albumin, selv når væsentlige 30 mængder kvældemiddel er sat til støbematerialet.The data in Table 2 clearly shows the pronounced effect of adding DMSO to the casting solution with respect to the degree of membrane swelling measured by membrane wet thickness and water content with resultant increase of membrane permeability to water and various solutes. The polycarbonate membrane made using the casting material containing no swelling agent exhibited permeability etching properties comparable to the characteristics of a typical "Cuprophan" PT150 membrane. Addition of the first amount of 10 DMSO swelling agent (2 g per 15 g polymer) to the casting material is seen to have almost doubled the water content and tripled the hydraulic permeability (measured by ultrafiltration rate) of the membrane, and to have increased permeability in all of the membrane. tested solutes. The degree of permeability increase increased with the molecular size of the solute, with 24-37% higher values being observed in the case of smaller amounts of solutes such as urea and creatinine, and a very clear increase of 160% was found for inulin which is a typical example of a solute in the upper "intermediate molecular" range. Further increase in the amount of swelling agent in the casting material (to 4 g per 15 g polymer) is seen to have increased the water content of the polydbonate membrane and the water permeability in tet further, with the permeabi1 in the density of solvents having lower molecular weight only slightly increased (2-7 %) (i.e. sodium chloride, urea, creatinine and uric acid), while there was still a significant increase in the "average molecule" permeability (22, 24 and 60% increase for phosphate, raffinose and inulin). Importantly, the polycarbonate membranes completely reject albumin, even when substantial amounts of swelling agent are added to the molding material.
Eksempel 3Example 3
Dette eksempel tjener til illustration af effektiviteten af 35 flere coopløsningsmidler - kvældemidler til forøgelse af po-lycarbonatmembranens permeabilitet, når de sættes til membran-støbeopløsningsmaterialet.This example serves to illustrate the effectiveness of 35 more co-solvents - swelling agents for increasing the permeability of the polycarbonate membrane when added to the membrane molding solvent.
DK 163482 BDK 163482 B
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Støbeopløsninger blev fremstillet ud fra følgende materiale under anvendelse af en polyether-polycarbonat-blokcopolymer, opnået ved omsætning af phosgen med en comonomerbland ing bestående af "bisphenol A" (75 vægt%) og "Carbowax 6000" (25 5 vægt%) og med et grænseviskositetstal (i chloroform ved 25*C) på 1,52 svarende til en molekylvægt på 301.000Castings were prepared from the following material using a polyether-polycarbonate block copolymer obtained by reaction of phosgene with a comonomer mixture consisting of "bisphenol A" (75 wt%) and "Carbowax 6000" (25 wt%) and with an intrinsic viscosity number (in chloroform at 25 ° C) of 1.52 corresponding to a molecular weight of 301,000
Komponent Vægt i g 10 Polyether-polycarbonat-blokcopolymer 40,0 1,3-dioxo1 an 256,2Component Weight in g 10 Polyether Polycarbonate Block Copolymer 40.0 1,3-Dioxolane 256.2
Kvældemiddel 8,0Nitrogen 8.0
Membraner blev fremstillet ud fra hvert materiale ved hjælp af 15 manuel støbning under identiske betingelser på glasplader ved stuetemperatur og ved gelatinering i vand ved 25°C efter varierende tørretider. De fysiske egenskaber og permeabi1 itetse-genskaberne bestemt for disse membraner er opført i tabel 3.Membranes were prepared from each material by manual casting under identical conditions on glass plates at room temperature and by gelatinization in water at 25 ° C after varying drying times. The physical properties and permeability properties determined for these membranes are listed in Table 3.
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Claims (11)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US45493974A | 1974-03-26 | 1974-03-26 | |
| US45493974 | 1974-03-26 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK96275A DK96275A (en) | 1975-09-27 |
| DK163482B true DK163482B (en) | 1992-03-09 |
| DK163482C DK163482C (en) | 1992-07-27 |
Family
ID=23806700
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK096275A DK163482C (en) | 1974-03-26 | 1975-03-10 | PROCEDURE FOR PREPARING A HYDROPHILIC POLYETHER-POLYCARBONATE MEMBRANE |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS5228826B2 (en) |
| BE (1) | BE826775A (en) |
| CA (1) | CA1062413A (en) |
| CH (1) | CH594434A5 (en) |
| DK (1) | DK163482C (en) |
| FR (1) | FR2265807B1 (en) |
| GB (1) | GB1500937A (en) |
| IT (1) | IT1030266B (en) |
| NL (1) | NL172920C (en) |
| NO (1) | NO135162C (en) |
| SE (1) | SE407583B (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1107467A (en) * | 1976-03-19 | 1981-08-25 | Paul A. Cantor | Polycarbonate membranes for use in hemodialysis |
| US4069151A (en) * | 1976-03-31 | 1978-01-17 | C. R. Bard, Inc. | Thin polycarbonate membranes for use in hemodialysis |
| DE2932761A1 (en) * | 1979-08-13 | 1981-02-26 | Akzo Gmbh | POLYCARBONATE-POLYAETHER-COPOLYMER MEMBRANE |
| SE423106B (en) * | 1980-07-25 | 1982-04-13 | Gambro Dialysatoren | PLASMAFERES MEMBRANE AND WAY TO MANUFACTURE THIS |
| ATE10437T1 (en) * | 1980-09-01 | 1984-12-15 | Gambro, Inc. | DRY POLYCARBONATE MEMBRANE AND METHOD OF MANUFACTURE. |
| EP0046816A1 (en) * | 1980-09-01 | 1982-03-10 | Gambro, Inc. | Polycarbonate hemofiltration membrane and method of hemofiltering using such a membrane |
| SE446505B (en) * | 1982-11-16 | 1986-09-22 | Gambro Dialysatoren | MEMBRANE AND WAY TO MAKE THIS |
| EP0135760A1 (en) * | 1983-08-19 | 1985-04-03 | Bayer Ag | Polyether-polycarbonates for dialysis-membranes |
| US20080143014A1 (en) * | 2006-12-18 | 2008-06-19 | Man-Wing Tang | Asymmetric Gas Separation Membranes with Superior Capabilities for Gas Separation |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3945926A (en) * | 1971-10-18 | 1976-03-23 | Chemical Systems, Inc. | Integral microporous high void volume polycarbonate membranes and a dry process for forming same |
| US3901810A (en) * | 1972-09-21 | 1975-08-26 | Calgon Corp | Ultrafiltration membranes |
-
1975
- 1975-02-28 GB GB8359/75A patent/GB1500937A/en not_active Expired
- 1975-03-04 IT IT67549/75A patent/IT1030266B/en active
- 1975-03-07 FR FR7507225A patent/FR2265807B1/fr not_active Expired
- 1975-03-10 DK DK096275A patent/DK163482C/en active
- 1975-03-11 NL NLAANVRAGE7502865,A patent/NL172920C/en not_active IP Right Cessation
- 1975-03-17 BE BE154410A patent/BE826775A/en not_active IP Right Cessation
- 1975-03-19 CA CA222,510A patent/CA1062413A/en not_active Expired
- 1975-03-19 CH CH353175A patent/CH594434A5/xx not_active IP Right Cessation
- 1975-03-24 NO NO751026A patent/NO135162C/no unknown
- 1975-03-25 SE SE7503430A patent/SE407583B/en not_active IP Right Cessation
- 1975-03-26 JP JP50036697A patent/JPS5228826B2/ja not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB1500937A (en) | 1978-02-15 |
| FR2265807A1 (en) | 1975-10-24 |
| IT1030266B (en) | 1979-03-30 |
| NL172920C (en) | 1983-11-16 |
| JPS5228826B2 (en) | 1977-07-28 |
| SE407583B (en) | 1979-04-02 |
| DK163482C (en) | 1992-07-27 |
| FR2265807B1 (en) | 1979-02-23 |
| BE826775A (en) | 1975-09-17 |
| NL7502865A (en) | 1975-09-30 |
| NO135162C (en) | 1977-02-23 |
| NO135162B (en) | 1976-11-15 |
| JPS5179172A (en) | 1976-07-09 |
| CH594434A5 (en) | 1978-01-13 |
| NO751026L (en) | 1975-09-29 |
| SE7503430L (en) | 1975-09-29 |
| NL172920B (en) | 1983-06-16 |
| CA1062413A (en) | 1979-09-18 |
| DK96275A (en) | 1975-09-27 |
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