CN117567790A - Medical polyurethane foam with procoagulant inner surface and anticoagulant outer surface and preparation method thereof - Google Patents
Medical polyurethane foam with procoagulant inner surface and anticoagulant outer surface and preparation method thereof Download PDFInfo
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- CN117567790A CN117567790A CN202410054205.1A CN202410054205A CN117567790A CN 117567790 A CN117567790 A CN 117567790A CN 202410054205 A CN202410054205 A CN 202410054205A CN 117567790 A CN117567790 A CN 117567790A
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- procoagulant
- polyurethane foam
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- diisocyanate
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- 229920005830 Polyurethane Foam Polymers 0.000 title claims abstract description 130
- 239000011496 polyurethane foam Substances 0.000 title claims abstract description 130
- 239000003805 procoagulant Substances 0.000 title claims abstract description 129
- 239000003146 anticoagulant agent Substances 0.000 title claims abstract description 45
- 229940127219 anticoagulant drug Drugs 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000000463 material Substances 0.000 claims abstract description 177
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 79
- 239000011248 coating agent Substances 0.000 claims abstract description 32
- 238000000576 coating method Methods 0.000 claims abstract description 32
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 30
- 229920002545 silicone oil Polymers 0.000 claims abstract description 22
- 230000010100 anticoagulation Effects 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 125000005442 diisocyanate group Chemical group 0.000 claims abstract description 8
- 239000004088 foaming agent Substances 0.000 claims abstract description 8
- 150000005846 sugar alcohols Polymers 0.000 claims abstract description 4
- 239000000243 solution Substances 0.000 claims description 92
- 238000004140 cleaning Methods 0.000 claims description 32
- 239000008213 purified water Substances 0.000 claims description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- 238000001179 sorption measurement Methods 0.000 claims description 19
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 18
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 18
- 229920001610 polycaprolactone Polymers 0.000 claims description 16
- 239000004632 polycaprolactone Substances 0.000 claims description 16
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 15
- DJOWTWWHMWQATC-KYHIUUMWSA-N Karpoxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1(O)C(C)(C)CC(O)CC1(C)O)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C DJOWTWWHMWQATC-KYHIUUMWSA-N 0.000 claims description 14
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 claims description 14
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 14
- 239000004626 polylactic acid Substances 0.000 claims description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 229920000954 Polyglycolide Polymers 0.000 claims description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 12
- 239000004633 polyglycolic acid Substances 0.000 claims description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 11
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 10
- 238000005187 foaming Methods 0.000 claims description 10
- 229940117841 methacrylic acid copolymer Drugs 0.000 claims description 10
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims description 10
- 238000006116 polymerization reaction Methods 0.000 claims description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 150000002009 diols Chemical class 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- KTLIZDDPOZZHCD-UHFFFAOYSA-N 3-(2-aminoethylamino)propan-1-ol Chemical compound NCCNCCCO KTLIZDDPOZZHCD-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- MYBGXHYNILTXRW-UHFFFAOYSA-N C(C(=C)C)(=O)OCCP(=O)=C(O)C[N+](C)(C)C.C(C(=C)C)(=O)[O-] Chemical compound C(C(=C)C)(=O)OCCP(=O)=C(O)C[N+](C)(C)C.C(C(=C)C)(=O)[O-] MYBGXHYNILTXRW-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- 239000005057 Hexamethylene diisocyanate Substances 0.000 claims description 6
- 239000005058 Isophorone diisocyanate Substances 0.000 claims description 6
- 229920000669 heparin Polymers 0.000 claims description 6
- 229960002897 heparin Drugs 0.000 claims description 6
- RRAMGCGOFNQTLD-UHFFFAOYSA-N hexamethylene diisocyanate Chemical compound O=C=NCCCCCCN=C=O RRAMGCGOFNQTLD-UHFFFAOYSA-N 0.000 claims description 6
- NIMLQBUJDJZYEJ-UHFFFAOYSA-N isophorone diisocyanate Chemical compound CC1(C)CC(N=C=O)CC(C)(CN=C=O)C1 NIMLQBUJDJZYEJ-UHFFFAOYSA-N 0.000 claims description 6
- -1 methacryloxyethyl Chemical group 0.000 claims description 6
- DVKJHBMWWAPEIU-UHFFFAOYSA-N toluene 2,4-diisocyanate Chemical class CC1=CC=C(N=C=O)C=C1N=C=O DVKJHBMWWAPEIU-UHFFFAOYSA-N 0.000 claims description 6
- QXJQHYBHAIHNGG-UHFFFAOYSA-N trimethylolethane Chemical compound OCC(C)(CO)CO QXJQHYBHAIHNGG-UHFFFAOYSA-N 0.000 claims description 6
- SHKUUQIDMUMQQK-UHFFFAOYSA-N 2-[4-(oxiran-2-ylmethoxy)butoxymethyl]oxirane Chemical compound C1OC1COCCCCOCC1CO1 SHKUUQIDMUMQQK-UHFFFAOYSA-N 0.000 claims description 5
- 229920002125 Sokalan® Polymers 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 239000004584 polyacrylic acid Substances 0.000 claims description 5
- VZXPHDGHQXLXJC-UHFFFAOYSA-N 1,6-diisocyanato-5,6-dimethylheptane Chemical compound O=C=NC(C)(C)C(C)CCCCN=C=O VZXPHDGHQXLXJC-UHFFFAOYSA-N 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
- 229920001661 Chitosan Polymers 0.000 claims description 4
- 102000008186 Collagen Human genes 0.000 claims description 4
- 108010035532 Collagen Proteins 0.000 claims description 4
- 108010010803 Gelatin Proteins 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 229920002845 Poly(methacrylic acid) Polymers 0.000 claims description 4
- 229920002873 Polyethylenimine Polymers 0.000 claims description 4
- 108010039918 Polylysine Proteins 0.000 claims description 4
- 229920006318 anionic polymer Polymers 0.000 claims description 4
- CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical compound CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 claims description 4
- 229920006317 cationic polymer Polymers 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 229920001436 collagen Polymers 0.000 claims description 4
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- 229920000159 gelatin Polymers 0.000 claims description 4
- 239000008273 gelatin Substances 0.000 claims description 4
- 235000019322 gelatine Nutrition 0.000 claims description 4
- 235000011852 gelatine desserts Nutrition 0.000 claims description 4
- 235000011187 glycerol Nutrition 0.000 claims description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 4
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 claims description 4
- 229920000656 polylysine Polymers 0.000 claims description 4
- 229920005862 polyol Polymers 0.000 claims description 4
- 150000003077 polyols Chemical class 0.000 claims description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 3
- 150000003863 ammonium salts Chemical group 0.000 claims description 3
- 235000010413 sodium alginate Nutrition 0.000 claims description 3
- 239000000661 sodium alginate Substances 0.000 claims description 3
- 229940005550 sodium alginate Drugs 0.000 claims description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 2
- 229920002674 hyaluronan Polymers 0.000 claims description 2
- 229960003160 hyaluronic acid Drugs 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 208000007536 Thrombosis Diseases 0.000 abstract description 20
- 210000004369 blood Anatomy 0.000 abstract description 19
- 239000008280 blood Substances 0.000 abstract description 19
- 230000015572 biosynthetic process Effects 0.000 abstract description 7
- 230000001737 promoting effect Effects 0.000 abstract description 3
- 230000023555 blood coagulation Effects 0.000 abstract description 2
- 239000012567 medical material Substances 0.000 abstract description 2
- 239000006260 foam Substances 0.000 description 16
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 12
- 238000011049 filling Methods 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 9
- 238000009738 saturating Methods 0.000 description 8
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 238000005507 spraying Methods 0.000 description 7
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- UKLDJPRMSDWDSL-UHFFFAOYSA-L [dibutyl(dodecanoyloxy)stannyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)O[Sn](CCCC)(CCCC)OC(=O)CCCCCCCCCCC UKLDJPRMSDWDSL-UHFFFAOYSA-L 0.000 description 6
- 239000012975 dibutyltin dilaurate Substances 0.000 description 6
- 239000012047 saturated solution Substances 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 108090000190 Thrombin Proteins 0.000 description 4
- ISKQADXMHQSTHK-UHFFFAOYSA-N [4-(aminomethyl)phenyl]methanamine Chemical compound NCC1=CC=C(CN)C=C1 ISKQADXMHQSTHK-UHFFFAOYSA-N 0.000 description 4
- 229960001701 chloroform Drugs 0.000 description 4
- 230000002526 effect on cardiovascular system Effects 0.000 description 4
- 229960004072 thrombin Drugs 0.000 description 4
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical compound [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 description 4
- 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 3
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- 230000004048 modification Effects 0.000 description 3
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- 206010002329 Aneurysm Diseases 0.000 description 2
- 206010046996 Varicose vein Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
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- 210000002381 plasma Anatomy 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000004971 Cross linker Substances 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
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Abstract
The invention discloses medical polyurethane foam with internal procoagulant blood and anticoagulation outer surface and a preparation method thereof, and relates to the technical field of medical material preparation, wherein the medical polyurethane foam comprises the following components in parts by weight: 10-80 parts of polyalcohol, 30-80 parts of diisocyanate, 0.1-5 parts of catalyst, 1-15 parts of silicone oil, 0-15 parts of foaming agent and 0.5-5 parts of water, and further comprises a procoagulant material A, a procoagulant material B, a cross-linking agent and an anticoagulant material coating solution. The invention also provides a preparation method of the medical polyurethane foam, which can prevent thrombus from falling off, has good safety and can be degraded, and effectively solves the problems that the capability of the common polyurethane foam material for promoting thrombus formation is insufficient and thrombus is easy to fall off.
Description
Technical Field
The invention relates to the technical field of medical material preparation, in particular to medical polyurethane foam with an internal procoagulant blood and an anticoagulant external surface and a preparation method thereof.
Background
Foam-based medical devices can maintain a temporary compressed shape so that they can be stored in a compressed state and delivered to a focal site via a catheter. The cost and complications of such minimally invasive interventions are significantly reduced compared to traditional open surgery.
The polyurethane foam material has excellent elasticity, water absorbability, degradability, low density and biocompatibility due to the porous structure, and has great development space in the field of cardiovascular plugging filling materials, such as left atrial appendage plugging materials, valve peripheral leakage prevention materials, varicose vein filling materials, aneurysm filling materials and the like.
After the foam is conveyed to the cardiovascular focus position, the foam can expand rapidly and absorb blood, the blood flow speed through the foam is reduced or even the blood flow cannot occur due to the complicated internal structure of the foam, and then thrombus is gradually formed, so that the focus position is plugged or filled.
Because the foam modulus is lower, the flexibility is good, the focus of the load geometric shape can be matched, for example, the left auricle with a complex inner cavity can be fully filled; the foam density is low, and the plugging filling is 1cm 3 The cavity of the material is only required to be less than 50mg, and the use amount of the material is reduced, so that better biosafety can be obtained; the foam has degradability, can realize tissue repair and regeneration of focus parts along with degradation of the foam and organization of internal thrombus, and has long-term biological safety.
However, during the thrombus formation inside the foam, the thrombus may expand indefinitely, and the contact of the outer surface of the foam with blood may induce thrombus formation, so that there is a risk of thrombus detachment, which may induce a series of complications. On the other hand, the polyurethane foam material has insufficient capability of promoting thrombosis, and anticoagulant drugs are used in the operation process, so that the blood absorbed into the foam can form thrombus only after a long time, and quick filling and plugging cannot be realized.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides the medical polyurethane foam with the anticoagulant inner procoagulant outer surface and the preparation method thereof, which can prevent thrombus from falling off, has good safety and can be degraded, and effectively solves the problems that the capability of common polyurethane foam material for promoting thrombus formation is insufficient and thrombus is easy to fall off.
In order to achieve the above purpose, the technical scheme adopted by the invention for solving the technical problems is as follows: the medical polyurethane foam for providing internal procoagulant external surface anticoagulation comprises the following components in parts by weight: 10-80 parts of polyalcohol, 30-80 parts of diisocyanate, 0.1-5 parts of catalyst, 1-15 parts of silicone oil, 0-15 parts of foaming agent and 0.5-5 parts of water, and further comprises a procoagulant material A, a procoagulant material B, a cross-linking agent and an anticoagulant material coating solution.
Further, the medical polyurethane foam with the anticoagulated inner procoagulant outer surface comprises the following components in parts by weight: 37 parts of polyol, 51 parts of diisocyanate, 1.3 parts of catalyst, 6.4 parts of silicone oil, 2.1 parts of foaming agent and 2.2 parts of water, and further comprises a procoagulant material A, a procoagulant material B, a crosslinking agent and an anticoagulant material coating solution.
Further, the polyhydric alcohol is at least one of polycaprolactone diol, polylactic acid diol, polyglycolic acid diol, polycaprolactone triol, polylactic acid triol, polyglycolic acid triol, polycaprolactone tetrol, polylactic acid tetrol, polyglycolic acid tetrol, butanediol, propylene glycol, ethylene glycol, triethanolamine, hydroxypropyl ethylenediamine, glycerol, pentaerythritol, trimethylolethane, and tris (hydroxymethyl) aminomethane.
Further, the diisocyanate is at least one of hexamethylene diisocyanate, trimethylhexamethylene diisocyanate, isophorone diisocyanate, hydrogenated toluene diisocyanate, methylene diphenyl diisocyanate, and lysine ethyl ester diisocyanate.
Further, the catalyst is a mixture of an organotin catalyst and an organoamine catalyst.
Further, the foaming agent is at least one of dichloromethane, chloroform and acetone.
Further, the preparation method of the procoagulant material A comprises the following steps: the cationic polymer is dissolved in an acidic aqueous solution to obtain procoagulant material a.
Further, the cationic polymer is at least one of collagen, gelatin, chitosan, polyethyleneimine, polyquaternium and polylysine.
Further, the concentration of cations in procoagulant material A is 0.1-5mg/mL.
Further, the acidic aqueous solution is one of a hydrogen chloride solution, an acetic acid solution and a formic acid solution.
Further, the concentration of the acidic aqueous solution is 0.1 to 5mol/L.
Further, the preparation method of the procoagulant material B comprises the following steps: the anionic polymer dissolves in water to give procoagulant material B.
Further, the anionic polymer is at least one of polyacrylic acid, polymethacrylic acid, hyaluronic acid and sodium alginate.
Further, the concentration of the procoagulant material B is 0.1-5mg/mL.
Further, the crosslinking agent is at least one of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, divinyl sulfone and 1, 4-butanediol diglycidyl ether.
Further, the preparation method of the anticoagulant material coating solution specifically comprises the following steps: dissolving an anticoagulant material in water, then adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, and reacting at room temperature to obtain an anticoagulant material coating solution.
Further, the anticoagulant material is at least one of heparin, methacryloxyethyl phosphorylcholine-methacrylic acid copolymer and methacryloxyethyl sulfobetaine-methacrylic acid copolymer.
Further, the concentration of the anticoagulant material in the anticoagulant material coating solution is 1-10mg/mL.
Further, the concentration of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride in the anticoagulant material coating solution is 1-10mg/mL.
Further, the concentration of N-hydroxysuccinimide in the anticoagulant material coating solution is 1-10mg/mL.
Further, the reaction was carried out at room temperature for 6 to 24 hours.
The beneficial effects of adopting the further scheme are as follows: activating the carboxyl group.
The preparation method of the medical polyurethane foam with the internal procoagulant blood and the anticoagulated external surface specifically comprises the following steps:
s1, mixing polyol and diisocyanate to prepare a prepolymer, and then adding a catalyst, silicone oil, a foaming agent and water to mix for polymerization foaming to obtain a polyurethane foam material;
s2, immersing the polyurethane foam material obtained in the step S1 in the procoagulant material A to saturate the adsorption solution, squeezing and cleaning with purified water, immersing the polyurethane foam material in the procoagulant material B to saturate the adsorption solution, squeezing and cleaning with purified water, and then placing the polyurethane foam material in the procoagulant material A to saturate the adsorption solution;
s3, repeating the operation of the step S2, dissolving a cross-linking agent in water to prepare a cross-linking agent solution, immersing the polyurethane foam material in the cross-linking agent solution to saturate the adsorption solution, and squeezing and cleaning with purified water to obtain the procoagulant polyurethane foam material;
s4, setting an anticoagulant material coating solution on the outer surface of the procoagulant polyurethane foam material obtained in the step S3, and extruding and cleaning with purified water after reaction to obtain the medical polyurethane foam with the anticoagulant inner procoagulant outer surface.
Further, in step S2, the adsorption solution is saturated for 8-12min.
Further, in step S3, the process is repeated 5 to 10 times.
Further, the concentration of the crosslinker solution is 0.1-5mg/mL.
Further, the adsorption solution is saturated for 4-6 hours.
Further, in step S4, the anticoagulant material coating solution is applied to the outer surface of the procoagulant polyurethane foam material by spraying or brushing.
Further, the reaction is carried out at 0-10 ℃ for 6-24h.
In summary, the invention has the following beneficial effects:
1. the medical polyurethane foam with the internal procoagulant blood and the anticoagulated external surface can absorb blood into the foam when contacting with blood, and the procoagulant blood coating is coated on the internal surface of the material, so that the internal thrombus formation can be promoted, and the plugging and filling can be realized; the anticoagulant material on the outer surface of the foam can inhibit thrombus formation on the outer surface, prevent thrombus from infinitely expanding and falling off, and has good safety; the porous and degradable performance can promote the repair and regeneration of tissues, and has long-term safety.
2. The medical polyurethane foam with the internal procoagulant blood and the anticoagulated external surface is suitable for plugging and filling materials in the cardiovascular fields such as left auricle plugging materials, valve peripheral leakage prevention materials, varicose vein filling materials, aneurysm filling materials and the like.
Drawings
FIG. 1 is a graph showing comparison of time results of activated partial thromboplastin;
FIG. 2 is a graph comparing thrombin time results;
FIG. 3 is a graph showing comparison of the results of the number of platelet adhesion.
Detailed Description
The present invention will be further described with reference to examples and drawings, but the present invention is not limited thereto.
Example 1
The medical polyurethane foam with the internal procoagulant outer surface anticoagulated blood comprises the following components in parts by weight: 30 parts of polycaprolactone diol, 7 parts of triethanolamine, 2.2 parts of water, 51 parts of hexamethylene diisocyanate, 1 part of dibutyltin dilaurate, 0.3 part of N-ethylmorpholine, 6.4 parts of silicone oil and 2.1 parts of methylene dichloride.
The medical polyurethane foam with the anticoagulated inner procoagulant outer surface further comprises procoagulant material A, procoagulant material B, a cross-linking agent and an anticoagulation material coating solution.
The preparation method of the medical polyurethane foam with the anticoagulated inner procoagulant outer surface comprises the following steps:
s1, mixing polycaprolactone dihydric alcohol, triethanolamine and hexamethylene diisocyanate to prepare a prepolymer, and then adding dibutyltin dilaurate, N-ethylmorpholine, silicone oil, methylene dichloride and water to mix for polymerization foaming to obtain a polyurethane foam material;
s2, dissolving collagen in a hydrogen chloride solution with the concentration of 2mg/mL to prepare a procoagulant material A, wherein the concentration of the collagen is 3mg/mL, immersing the polyurethane foam material obtained in the step S1 in the procoagulant material A, saturating the adsorption solution for 10min, squeezing and cleaning with purified water, dissolving polyacrylic acid in the water to prepare a procoagulant material B with the concentration of 1mg/mL, immersing the polyurethane foam material in the procoagulant material B, saturating the adsorption solution for 10min, squeezing and cleaning with purified water, and then saturating the adsorption solution in the procoagulant material A for 10min;
s3, repeating the operation of the step S2 for 10 times, dissolving 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride in water to prepare a cross-linking agent solution of 2mg/mL, immersing the polyurethane foam material in the cross-linking agent solution to saturate the solution for 5 hours, and squeezing and cleaning the polyurethane foam material with purified water to obtain the procoagulant polyurethane foam material;
s4, dissolving heparin in water, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, reacting for 24 hours at room temperature to activate carboxyl groups, obtaining an anticoagulant material coating solution, wherein the concentration of heparin is 5mg/mL, the concentration of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 5mg/mL, the concentration of N-hydroxysuccinimide is 5mg/mL, spraying the anticoagulant material coating solution on the outer surface of the procoagulant polyurethane foam material, reacting for 24 hours at 4 ℃, and then squeezing and cleaning with purified water to obtain the medical polyurethane foam with the anticoagulant inner procoagulant outer surface.
Example 2
The medical polyurethane foam with the internal procoagulant outer surface anticoagulated blood comprises the following components in parts by weight: 28 parts of polylactic acid triol, 2 parts of ethylene glycol, 5 parts of triethanolamine, 2.2 parts of water, 55 parts of isophorone diisocyanate, 0.5 part of dibutyltin diacetate, 1 part of triethylenediamine, 6.2 parts of silicone oil and 0.1 part of methylene dichloride.
The medical polyurethane foam with the anticoagulated inner procoagulant outer surface further comprises procoagulant material A, procoagulant material B, a cross-linking agent and an anticoagulation material coating solution.
The preparation method of the medical polyurethane foam with the anticoagulated inner procoagulant outer surface comprises the following steps:
s1, mixing polylactic acid triol, ethylene glycol, triethanolamine and isophorone diisocyanate to prepare a prepolymer, and then adding dibutyl tin diacetate, triethylenediamine, silicone oil, methylene dichloride and water to mix for polymerization foaming to obtain a polyurethane foam material;
s2, dissolving chitosan in acetic acid solution with the concentration of 3mg/mL to prepare procoagulant material A, wherein the concentration of chitosan is 1mg/mL, immersing the polyurethane foam material obtained in the step S1 in the procoagulant material A, saturating the adsorption solution for 10min, squeezing and cleaning with purified water, dissolving polymethacrylic acid in the water to prepare procoagulant material B with the concentration of 1mg/mL, immersing the polyurethane foam material in the procoagulant material B, saturating the adsorption solution for 10min, squeezing and cleaning with purified water, and then saturating the adsorption solution in the procoagulant material A for 10min;
s3, repeating the operation of the step S2 for 8 times, dissolving 1, 4-butanediol diglycidyl ether in water to prepare a cross-linking agent solution of 2mg/mL, immersing the polyurethane foam material in the cross-linking agent solution to saturate the solution for 5 hours, and squeezing and cleaning the polyurethane foam material with purified water to obtain the procoagulant polyurethane foam material;
s4, dissolving methacryloxyethyl phosphorylcholine-methacrylic acid in water, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, reacting for 24 hours at room temperature to activate carboxyl groups, obtaining an anticoagulant material coating solution, wherein the concentration of the methacryloxyethyl phosphorylcholine-methacrylic acid is 2mg/mL, the concentration of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 8mg/mL, the concentration of the N-hydroxysuccinimide is 8mg/mL, spraying the anticoagulant material coating solution on the outer surface of the procoagulant polyurethane foam material, reacting for 24 hours at 6 ℃, and then squeezing and cleaning with purified water to obtain the medical polyurethane foam with the anticoagulant inner procoagulant outer surface.
Example 3
The medical polyurethane foam with the internal procoagulant outer surface anticoagulated blood comprises the following components in parts by weight: 10 parts of polylactic acid dihydric alcohol, 10 parts of butanediol, 10 parts of polyglycolic acid dihydric alcohol, 0.5 part of water, 30 parts of hydrogenated toluene diisocyanate, 0.05 part of stannous octoate, 0.05 part of N-ethyl morpholine, 1 part of silicone oil and 1 part of trichloromethane.
The medical polyurethane foam with the anticoagulated inner procoagulant outer surface further comprises procoagulant material A, procoagulant material B, a cross-linking agent and an anticoagulation material coating solution.
The preparation method of the medical polyurethane foam with the anticoagulated inner procoagulant outer surface comprises the following steps:
s1, mixing polylactic acid dihydric alcohol, butanediol, polyglycolic acid dihydric alcohol and hydrogenated toluene diisocyanate to prepare a prepolymer, and then adding stannous octoate, N-ethyl morpholine, silicone oil, chloroform and water to mix for polymerization foaming to obtain a polyurethane foam material;
s2, dissolving gelatin in a formic acid solution with the concentration of 0.1mg/mL to prepare a procoagulant material A, wherein the concentration of gelatin is 0.1mg/mL, immersing the polyurethane foam material obtained in the step S1 in the saturated solution for 8min, squeezing and cleaning with purified water, dissolving polymethacrylic acid in water to prepare a procoagulant material B with the concentration of 0.11mg/mL, immersing the polyurethane foam material in the saturated solution for 8min, squeezing and cleaning with purified water, and then placing the polyurethane foam material into the saturated solution for 8min;
s3, repeating the operation of the step S2 for 10 times, dissolving divinyl sulfone in water to prepare a cross-linking agent solution of 0.1mg/mL, immersing the polyurethane foam material in the cross-linking agent solution to saturate the solution for 4 hours, and squeezing and cleaning the polyurethane foam material with purified water to obtain a procoagulant polyurethane foam material;
s4, dissolving the methacryloyl ethyl sulfobetaine-methacrylic acid copolymer in water, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, reacting for 6 hours at room temperature to activate carboxyl groups, obtaining an anticoagulant material coating solution, wherein the concentration of the methacryloyl ethyl sulfobetaine-methacrylic acid copolymer is 5mg/mL, the concentration of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 5mg/mL, the concentration of the N-hydroxysuccinimide is 5mg/mL, spraying the anticoagulant material solution on the outer surface of the procoagulant polyurethane foam material, reacting for 6 hours at 0 ℃, and then squeezing and cleaning with purified water to obtain the medical polyurethane foam with the anticoagulant inner procoagulant outer surface.
Example 4
The medical polyurethane foam with the internal procoagulant outer surface anticoagulated blood comprises the following components in parts by weight: 30 parts of polycaprolactone tetrol, 10 parts of hydroxypropyl ethylenediamine, 20 parts of trimethylolethane, 3 parts of water, 60 parts of methylene diphenyl diisocyanate, 2 parts of dibutyltin diacetate, 1 part of N-methyl morpholine and 10 parts of silicone oil.
The medical polyurethane foam with the anticoagulated inner procoagulant outer surface further comprises procoagulant material A, procoagulant material B, a cross-linking agent and an anticoagulation material coating solution.
The preparation method of the medical polyurethane foam with the anticoagulated inner procoagulant outer surface comprises the following steps:
s1, mixing polycaprolactone tetrol, hydroxypropyl ethylenediamine, trimethylolethane and methylene diphenyl diisocyanate to prepare a prepolymer, and then adding dibutyltin diacetate, N-methyl morpholine, silicone oil and water to mix for polymerization foaming to obtain a polyurethane foam material;
s2, dissolving polyethyleneimine in an acetic acid solution with the concentration of 5mg/mL to prepare a procoagulant material A, wherein the concentration of polyethyleneimine is 5mg/mL, immersing the polyurethane foam material obtained in the step S1 in the procoagulant material A, saturating the adsorption solution for 12min, squeezing and cleaning with purified water, then dissolving sodium alginate in water to prepare a procoagulant material B with the concentration of 2mg/mL, immersing the polyurethane foam material in the procoagulant material B, saturating the adsorption solution for 12min, squeezing and cleaning with purified water, and then placing the polyurethane foam material into the procoagulant material A to saturate the adsorption solution for 12min;
s3, repeating the operation of the step S2 for 10 times, dissolving 1, 4-butanediol diglycidyl ether in water to prepare a cross-linking agent solution of 2mg/mL, immersing the polyurethane foam material in the cross-linking agent solution to saturate the solution for 5 hours, and squeezing and cleaning the polyurethane foam material with purified water to obtain the procoagulant polyurethane foam material;
s4, dissolving a methacryloxyethyl phosphorylcholine-methacrylic acid copolymer in water, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, reacting for 12 hours at room temperature to activate carboxyl groups, obtaining an anticoagulant material coating solution, wherein the concentration of the methacryloxyethyl phosphorylcholine-methacrylic acid copolymer is 5mg/mL, the concentration of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 5mg/mL, the concentration of the N-hydroxysuccinimide is 5mg/mL, spraying the anticoagulant material coating solution on the outer surface of the procoagulant polyurethane foam material, reacting for 12 hours at 5 ℃, and then squeezing and cleaning with purified water to obtain the medical polyurethane foam with the anticoagulant inner procoagulant outer surface.
Example 5
The medical polyurethane foam with the internal procoagulant outer surface anticoagulated blood comprises the following components in parts by weight: 30 parts of polycaprolactone tetrol, 10 parts of hydroxypropyl ethylenediamine, 20 parts of trimethylolethane, 10 parts of pentaerythritol, 10 parts of polyglycolic acid triol, 5 parts of water, 60 parts of methylene diphenyl diisocyanate, 20 parts of lysine ethyl diisocyanate, 2 parts of stannous octoate, 3 parts of N-methyl morpholine, 15 parts of silicone oil and 15 parts of acetone.
The medical polyurethane foam with the anticoagulated inner procoagulant outer surface further comprises procoagulant material A, procoagulant material B, a cross-linking agent and an anticoagulation material coating solution.
The preparation method of the medical polyurethane foam with the anticoagulated inner procoagulant outer surface comprises the following steps:
s1, mixing polycaprolactone tetrol, hydroxypropyl ethylenediamine, trimethylolethane, pentaerythritol, polyglycolic acid triol, methylene diphenyl diisocyanate and lysine ethyl ester diisocyanate to prepare a prepolymer, and then adding stannous octoate, N-methyl morpholine, silicone oil, acetone and water to mix for polymerization foaming to obtain a polyurethane foam material;
s2, dissolving polylysine in a hydrogen chloride solution with the concentration of 1mg/mL to prepare a procoagulant material A, wherein the concentration of polylysine is 3mg/mL, immersing the polyurethane foam material obtained in the step S1 in the saturated solution for 10min, squeezing and cleaning with purified water, then dissolving polyacrylic acid in water to prepare a procoagulant material B with the concentration of 5mg/mL, immersing the polyurethane foam material in the procoagulant material B to saturate the adsorbed solution for 10min, squeezing and cleaning with purified water, and then placing the polyurethane foam material into the procoagulant material A to saturate the adsorbed solution for 10min;
s3, repeating the operation of the step S2 for 10 times, dissolving 1, 4-butanediol diglycidyl ether in water to prepare a 5mg/mL cross-linking agent solution, immersing the polyurethane foam material in the cross-linking agent solution to saturate the solution for 6 hours, and squeezing and cleaning the polyurethane foam material with purified water to obtain the procoagulant polyurethane foam material;
s4, dissolving heparin in water, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, reacting for 24 hours at room temperature to activate carboxyl groups, obtaining an anticoagulant material coating solution, wherein the concentration of heparin is 10mg/mL, the concentration of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 10mg/mL, the concentration of N-hydroxysuccinimide is 10mg/mL, spraying the anticoagulant material coating solution on the outer surface of the procoagulant polyurethane foam material, reacting for 24 hours at 10 ℃, and then squeezing and cleaning with purified water to obtain the medical polyurethane foam with the anticoagulant inner procoagulant outer surface.
Example 6
The medical polyurethane foam with the internal procoagulant outer surface anticoagulated blood comprises the following components in parts by weight: 20 parts of polycaprolactone triol, 10 parts of polylactic acid tetrol, 20 parts of polyglycolic acid tetrol, 10 parts of propylene glycol, 10 parts of glycerin, 10 parts of tris (hydroxymethyl) aminomethane, 3 parts of water, 30 parts of trimethyl hexamethylene diisocyanate, 30 parts of toluene diisocyanate, 1 part of dibutyltin dilaurate, 4 parts of triethylenediamine and 12 parts of silicone oil.
The medical polyurethane foam with the anticoagulated inner procoagulant outer surface further comprises procoagulant material A, procoagulant material B, a cross-linking agent and an anticoagulation material coating solution.
The preparation method of the medical polyurethane foam with the anticoagulated inner procoagulant outer surface comprises the following steps:
s1, mixing polycaprolactone triol, polylactic acid tetrol, polyglycolic acid tetrol, propylene glycol, glycerol, tris (hydroxymethyl) aminomethane, trimethyl hexamethylene diisocyanate and toluene diisocyanate to prepare a prepolymer, and then adding dibutyl tin dilaurate, triethylenediamine, silicone oil and water to mix for polymerization foaming to obtain a polyurethane foam material;
s2, dissolving polyquaternary ammonium salt in a formic acid solution with the concentration of 4mg/mL to prepare a procoagulant material A, wherein the concentration of the polyquaternary ammonium salt is 2mg/mL, immersing the polyurethane foam material obtained in the step S1 in the saturated solution for 10min, squeezing and cleaning with purified water, then dissolving polyacrylic acid in water to prepare a procoagulant material B with the concentration of 4mg/mL, immersing the polyurethane foam material in the procoagulant material B to saturate the adsorbed solution for 10min, squeezing and cleaning with purified water, and then placing the polyurethane foam material into the saturated solution of the procoagulant material A to saturate the adsorbed solution for 10min;
s3, repeating the operation of the step S2 for 10 times, dissolving divinyl sulfone in water to prepare a cross-linking agent solution of 2mg/mL, immersing the polyurethane foam material in the cross-linking agent solution to saturate the solution for 5 hours, and squeezing and cleaning the polyurethane foam material with purified water to obtain a procoagulant polyurethane foam material;
s4, dissolving the methacryloyl ethyl sulfobetaine-methacrylic acid copolymer in water, adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, reacting for 12 hours at room temperature to activate carboxyl groups, obtaining an anticoagulant material coating solution, wherein the concentration of the methacryloyl ethyl sulfobetaine-methacrylic acid copolymer is 6mg/mL, the concentration of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 8mg/mL, the concentration of the N-hydroxysuccinimide is 5mg/mL, spraying the anticoagulant material coating solution on the outer surface of the procoagulant polyurethane foam material, reacting for 12 hours at 5 ℃, and then squeezing and cleaning with purified water to obtain the medical polyurethane foam with the anticoagulant inner procoagulant outer surface.
Comparative example 1
The polyurethane foam comprises the following components in parts by weight: 30 parts of polycaprolactone diol, 7 parts of triethanolamine, 2.2 parts of water, 51 parts of hexamethylene diisocyanate, 1.3 parts of dibutyltin dilaurate, 6.4 parts of silicone oil and 2.1 parts of dichloromethane.
The preparation method of the polyurethane foam comprises the following steps:
s1, mixing polycaprolactone dihydric alcohol, triethanolamine and hexamethylene diisocyanate for 12 hours to obtain a prepolymer;
s2, adding water, dibutyl tin dilaurate, silicone oil and methylene dichloride into the prepolymer obtained in the step S1, quickly mixing, and performing polymerization foaming to obtain the polyurethane foam.
Comparative example 2
The polyurethane foam comprises the following components in parts by weight: 28 parts of polylactic acid triol, 2 parts of ethylene glycol, 5 parts of triethanolamine, 2.2 parts of water, 55 parts of isophorone diisocyanate, 1.5 parts of N-ethyl morpholine, 6.2 parts of silicone oil and 0.1 part of trichloromethane.
The preparation method of the polyurethane foam comprises the following steps:
s1, mixing polylactic acid triol, ethylene glycol, triethanolamine and isophorone diisocyanate for 24 hours to obtain a prepolymer;
s2, adding water, N-ethyl morpholine, silicone oil and methylene dichloride into the prepolymer obtained in the step S1, quickly mixing, and performing polymerization foaming to obtain the polyurethane foam.
Test example 1
To investigate the procoagulant properties of the internal procoagulant external surface anticoagulant medical polyurethane foam surfaces obtained in example 1 and example 2, the Activated Partial Thromboplastin Time (APTT) and Thrombin Time (TT) were entered by a semi-automatic coagulometer (ACL 200,Instrumentation Laboratory Co,USA)And (5) evaluating rows. Platelet Poor Plasma (PPP) was obtained by centrifuging whole blood for 15 min. To determine APTT and TT, 1cm each was used 3 The medical polyurethane foams obtained in examples 1 and 2 and the polyurethane foams obtained in comparative examples 1 and 2 were immersed in 1000. Mu.L of PPP at 37℃for 45 minutes, then PPP was extruded, 100. Mu.L of the extruded PPP was mixed with 200. Mu.L of a test thrombin test reagent at 37℃for 5 minutes, and APTT and TT of plasma were monitored, and the results are shown in FIGS. 1-2, wherein 1, 2, 3 and 4 are experimental results of example 1, example 2, comparative example 1 and comparative example 2, respectively.
As can be seen from fig. 1-2, compared with the polyurethane foam without procoagulant modification, the Activated Partial Thromboplastin Time (APTT) and Thrombin Time (TT) of the polyurethane foam provided by the invention are significantly reduced, which means that the blood coagulation time in the foam is significantly reduced, and the modified polyurethane foam can realize faster thrombosis and faster filling and plugging when applied to the cardiovascular field.
Test example 2
Platelet Rich Plasma (PRP) was obtained by centrifuging fresh whole blood with 500rcf for 15 min. Static platelet analysis was performed in a 24-well plate, and after cutting the medical polyurethane foam for internal procoagulant external surface anticoagulation obtained in example 1 and example 2 and the polyurethane foam obtained in comparative example 1 and comparative example 2 into 1cm×1cm×0.2 cm-sized sheet-like samples, immersing in 500 μl PRP at 37 ℃ for 1h, washing the samples with 0.9wt% sodium chloride solution for 10min, and then gently washing the samples with 0.9wt% sodium chloride solution to remove non-adhered platelets, fixing with 2.5wt% glutaraldehyde solution at 4 ℃ overnight. The number of platelets adhered to the outer surface of the foam was observed and recorded by a scanning electron microscope (Nova Nano SEM450 (FEI, usa)), and the results are shown in fig. 3, wherein 1, 2, 3 and 4 are experimental results of example 1, example 2, comparative example 1 and comparative example 2, respectively.
As can be seen from fig. 3, the number of platelets adhered to the outer surface of the modified polyurethane foam is significantly reduced compared to the polyurethane foam without procoagulant modification, indicating that the modified polyurethane foam has an outermost surface which is an anticoagulant surface, can inhibit thrombus formation, prevents thrombus from infinitely expanding and falling off, and has good safety.
Although specific embodiments of the invention have been described in detail with reference to the accompanying drawings, it should not be construed as limiting the scope of protection of the present patent. Various modifications and variations which may be made by those skilled in the art without the creative effort are within the scope of the patent described in the claims.
Claims (10)
1. The medical polyurethane foam with the anticoagulated inner procoagulant outer surface is characterized by comprising the following components in parts by weight: 10-80 parts of polyalcohol, 30-80 parts of diisocyanate, 0.1-5 parts of catalyst, 1-15 parts of silicone oil, 0-15 parts of foaming agent and 0.5-5 parts of water;
also included are procoagulant material A, procoagulant material B, a cross-linking agent and a coating solution of anticoagulant material.
2. The internal procoagulant external surface anticoagulated medical polyurethane foam according to claim 1, wherein the polyol is at least one of polycaprolactone diol, polylactic acid diol, polyglycolic acid diol, polycaprolactone triol, polylactic acid triol, polyglycolic acid triol, polycaprolactone tetrol, polylactic acid tetrol, polyglycolic acid tetrol, butanediol, propylene glycol, ethylene glycol, triethanolamine, hydroxypropyl ethylenediamine, glycerol, pentaerythritol, trimethylolethane, and tris (hydroxymethyl) aminomethane.
3. The internal procoagulant external surface anticoagulated medical polyurethane foam according to claim 1, wherein the diisocyanate is at least one of hexamethylene diisocyanate, trimethylhexamethylene diisocyanate, isophorone diisocyanate, hydrogenated toluene diisocyanate, methylene diphenyl diisocyanate and lysine ethyl ester diisocyanate.
4. The medical polyurethane foam having an internal procoagulant exterior surface for anticoagulation according to claim 1, wherein the catalyst is a mixture of organotin-based catalyst and organoamine-based catalyst; the foaming agent is at least one of dichloromethane, chloroform and acetone.
5. The medical polyurethane foam having an internal procoagulant exterior surface for anticoagulation according to claim 1, wherein the procoagulant material a is prepared by the following method: dissolving a cationic polymer in an acidic aqueous solution to obtain a procoagulant material A; the cationic polymer is at least one of collagen, gelatin, chitosan, polyethyleneimine, polyquaternary ammonium salt and polylysine; the acidic aqueous solution is one of a hydrogen chloride solution, an acetic acid solution and a formic acid solution.
6. The medical polyurethane foam having an internal procoagulant exterior surface for anticoagulation according to claim 1, wherein the procoagulant material B is prepared by the following method: the anionic polymer is dissolved in water to obtain procoagulant material B; the anionic polymer is at least one of polyacrylic acid, polymethacrylic acid, hyaluronic acid and sodium alginate.
7. The medical polyurethane foam having an internal procoagulant exterior surface anticoagulated according to claim 1, wherein the cross-linking agent is at least one of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, divinyl sulfone and 1, 4-butanediol diglycidyl ether.
8. The medical polyurethane foam for internal procoagulant external surface anticoagulation according to claim 1, wherein the preparation method of the anticoagulation material coating solution comprises the following steps: dissolving an anticoagulant material in water, then adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, and reacting at room temperature to obtain an anticoagulant material coating solution.
9. The medical polyurethane foam having an internal procoagulant exterior surface anticoagulated according to claim 8, wherein the anticoagulation material is at least one of heparin, methacryloxyethyl phosphorylcholine-methacrylic acid copolymer and methacryloxyethyl sulfobetaine-methacrylic acid copolymer.
10. A process for the preparation of a medical polyurethane foam having an internal procoagulant external surface anticoagulated according to any one of claims 1-9, comprising in particular the following steps:
s1, mixing polyol and diisocyanate to prepare a prepolymer, and then adding a catalyst, silicone oil, a foaming agent and water to mix for polymerization foaming to obtain a polyurethane foam material;
s2, immersing the polyurethane foam material obtained in the step S1 in the procoagulant material A to saturate the adsorption solution, squeezing and cleaning with purified water, immersing the polyurethane foam material in the procoagulant material B to saturate the adsorption solution, squeezing and cleaning with purified water, and then placing the polyurethane foam material in the procoagulant material A to saturate the adsorption solution;
s3, repeating the operation of the step S2, dissolving a cross-linking agent in water to prepare a cross-linking agent solution, immersing the polyurethane foam material in the cross-linking agent solution to saturate the adsorption solution, and squeezing and cleaning with purified water to obtain the procoagulant polyurethane foam material;
s4, setting an anticoagulant material coating solution on the outer surface of the procoagulant polyurethane foam material obtained in the step S3, and extruding and cleaning with purified water after reaction to obtain the medical polyurethane foam with the anticoagulant inner procoagulant outer surface.
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