CN114699564A - Adhesion-enhanced lubricating coating, application thereof and medical interventional catheter - Google Patents
Adhesion-enhanced lubricating coating, application thereof and medical interventional catheter Download PDFInfo
- Publication number
- CN114699564A CN114699564A CN202210415649.4A CN202210415649A CN114699564A CN 114699564 A CN114699564 A CN 114699564A CN 202210415649 A CN202210415649 A CN 202210415649A CN 114699564 A CN114699564 A CN 114699564A
- Authority
- CN
- China
- Prior art keywords
- coating
- photo
- adhesion
- lubricating
- anion
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000576 coating method Methods 0.000 title claims abstract description 229
- 239000011248 coating agent Substances 0.000 title claims abstract description 225
- 230000001050 lubricating effect Effects 0.000 title claims abstract description 102
- 239000000126 substance Substances 0.000 claims abstract description 71
- 239000002987 primer (paints) Substances 0.000 claims abstract description 70
- 239000010410 layer Substances 0.000 claims abstract description 67
- 125000002091 cationic group Chemical group 0.000 claims abstract description 42
- 239000002904 solvent Substances 0.000 claims abstract description 31
- 229920001477 hydrophilic polymer Polymers 0.000 claims abstract description 28
- 239000000178 monomer Substances 0.000 claims abstract description 28
- 125000000129 anionic group Chemical group 0.000 claims abstract description 20
- 239000002994 raw material Substances 0.000 claims abstract description 14
- 239000002345 surface coating layer Substances 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims description 80
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- 238000001723 curing Methods 0.000 claims description 30
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 27
- 239000007864 aqueous solution Substances 0.000 claims description 22
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 claims description 17
- 229910052753 mercury Inorganic materials 0.000 claims description 17
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 16
- 150000001450 anions Chemical class 0.000 claims description 16
- 239000002244 precipitate Substances 0.000 claims description 15
- -1 4-benzoylbenzyl Chemical group 0.000 claims description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000002202 Polyethylene glycol Substances 0.000 claims description 11
- 150000001768 cations Chemical class 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 229920001223 polyethylene glycol Polymers 0.000 claims description 11
- XFCMNSHQOZQILR-UHFFFAOYSA-N 2-[2-(2-methylprop-2-enoyloxy)ethoxy]ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCOCCOC(=O)C(C)=C XFCMNSHQOZQILR-UHFFFAOYSA-N 0.000 claims description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 10
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 10
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 10
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 10
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- 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 7
- 229920002674 hyaluronan Polymers 0.000 claims description 7
- 229960003160 hyaluronic acid Drugs 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 6
- 239000011247 coating layer Substances 0.000 claims description 6
- KANJSNBRCNMZMV-ABRZTLGGSA-N fondaparinux Chemical compound O[C@@H]1[C@@H](NS(O)(=O)=O)[C@@H](OC)O[C@H](COS(O)(=O)=O)[C@H]1O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O4)NS(O)(=O)=O)[C@H](O3)C(O)=O)O)[C@@H](COS(O)(=O)=O)O2)NS(O)(=O)=O)[C@H](C(O)=O)O1 KANJSNBRCNMZMV-ABRZTLGGSA-N 0.000 claims description 6
- 229960001318 fondaparinux Drugs 0.000 claims description 6
- 229920000669 heparin Polymers 0.000 claims description 6
- 239000003055 low molecular weight heparin Substances 0.000 claims description 6
- 229940127215 low-molecular weight heparin Drugs 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- GTELLNMUWNJXMQ-UHFFFAOYSA-N 2-ethyl-2-(hydroxymethyl)propane-1,3-diol;prop-2-enoic acid Chemical class OC(=O)C=C.OC(=O)C=C.OC(=O)C=C.CCC(CO)(CO)CO GTELLNMUWNJXMQ-UHFFFAOYSA-N 0.000 claims description 5
- 229920002567 Chondroitin Polymers 0.000 claims description 5
- DAKWPKUUDNSNPN-UHFFFAOYSA-N Trimethylolpropane triacrylate Chemical compound C=CC(=O)OCC(CC)(COC(=O)C=C)COC(=O)C=C DAKWPKUUDNSNPN-UHFFFAOYSA-N 0.000 claims description 5
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 claims description 5
- 239000004952 Polyamide Substances 0.000 claims description 4
- 230000005540 biological transmission Effects 0.000 claims description 4
- 125000004386 diacrylate group Chemical group 0.000 claims description 4
- 238000011068 loading method Methods 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 229920002401 polyacrylamide Polymers 0.000 claims description 4
- 229920002647 polyamide Polymers 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 3
- 229920000045 Dermatan sulfate Polymers 0.000 claims description 3
- 229920000288 Keratan sulfate Polymers 0.000 claims description 3
- 239000004695 Polyether sulfone Substances 0.000 claims description 3
- 239000004697 Polyetherimide Substances 0.000 claims description 3
- 239000004642 Polyimide Substances 0.000 claims description 3
- 229920002125 Sokalan® Polymers 0.000 claims description 3
- OKKRPWIIYQTPQF-UHFFFAOYSA-N Trimethylolpropane trimethacrylate Chemical compound CC(=C)C(=O)OCC(CC)(COC(=O)C(C)=C)COC(=O)C(C)=C OKKRPWIIYQTPQF-UHFFFAOYSA-N 0.000 claims description 3
- 229960004969 dalteparin Drugs 0.000 claims description 3
- 229940051593 dermatan sulfate Drugs 0.000 claims description 3
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 claims description 3
- 238000007598 dipping method Methods 0.000 claims description 3
- 229960000610 enoxaparin Drugs 0.000 claims description 3
- KXCLCNHUUKTANI-RBIYJLQWSA-N keratan Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@H](COS(O)(=O)=O)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@H](O[C@@H](O[C@H]3[C@H]([C@@H](COS(O)(=O)=O)O[C@@H](O)[C@@H]3O)O)[C@H](NC(C)=O)[C@H]2O)COS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@@H]1O KXCLCNHUUKTANI-RBIYJLQWSA-N 0.000 claims description 3
- 229960000899 nadroparin Drugs 0.000 claims description 3
- 239000004584 polyacrylic acid Substances 0.000 claims description 3
- 229920006393 polyether sulfone Polymers 0.000 claims description 3
- 229920001601 polyetherimide Polymers 0.000 claims description 3
- 229920001721 polyimide Polymers 0.000 claims description 3
- 238000004528 spin coating Methods 0.000 claims description 3
- 238000005507 spraying Methods 0.000 claims description 3
- UWMYPAGPLYUAMK-UHFFFAOYSA-M [4-[4-(diethylamino)benzoyl]phenyl]-diethyl-octylazanium iodide Chemical compound [I-].C(C)N(C1=CC=C(C(=O)C2=CC=C(C=C2)[N+](CCCCCCCC)(CC)CC)C=C1)CC UWMYPAGPLYUAMK-UHFFFAOYSA-M 0.000 claims description 2
- 238000004108 freeze drying Methods 0.000 claims description 2
- 230000001376 precipitating effect Effects 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 22
- 239000000463 material Substances 0.000 abstract description 21
- 229920000642 polymer Polymers 0.000 abstract description 16
- 239000002318 adhesion promoter Substances 0.000 abstract description 7
- 238000004132 cross linking Methods 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 6
- 238000005299 abrasion Methods 0.000 abstract description 3
- 208000035143 Bacterial infection Diseases 0.000 abstract description 2
- 208000022362 bacterial infectious disease Diseases 0.000 abstract description 2
- 239000002344 surface layer Substances 0.000 abstract description 2
- 230000005923 long-lasting effect Effects 0.000 abstract 1
- 230000006870 function Effects 0.000 description 18
- 239000000758 substrate Substances 0.000 description 18
- 241000894006 Bacteria Species 0.000 description 16
- 239000008367 deionised water Substances 0.000 description 14
- 229910021641 deionized water Inorganic materials 0.000 description 14
- 238000004140 cleaning Methods 0.000 description 12
- 239000003999 initiator Substances 0.000 description 12
- 230000014759 maintenance of location Effects 0.000 description 10
- 239000004814 polyurethane Substances 0.000 description 10
- 238000001990 intravenous administration Methods 0.000 description 9
- 229920002635 polyurethane Polymers 0.000 description 9
- 239000004800 polyvinyl chloride Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000005461 lubrication Methods 0.000 description 7
- 229920000915 polyvinyl chloride Polymers 0.000 description 7
- 238000001556 precipitation Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 239000008199 coating composition Substances 0.000 description 6
- 239000002131 composite material Substances 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 230000010065 bacterial adhesion Effects 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 238000000016 photochemical curing Methods 0.000 description 5
- 238000001179 sorption measurement Methods 0.000 description 5
- 229910021642 ultra pure water Inorganic materials 0.000 description 5
- 239000012498 ultrapure water Substances 0.000 description 5
- 238000004506 ultrasonic cleaning Methods 0.000 description 5
- 239000004698 Polyethylene Substances 0.000 description 4
- 239000004743 Polypropylene Substances 0.000 description 4
- 229920002385 Sodium hyaluronate Polymers 0.000 description 4
- 238000004364 calculation method Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 230000005012 migration Effects 0.000 description 4
- 238000013508 migration Methods 0.000 description 4
- 229920000573 polyethylene Polymers 0.000 description 4
- 229920001155 polypropylene Polymers 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 229940010747 sodium hyaluronate Drugs 0.000 description 4
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(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- Chemical compound [Na+].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 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 4
- 230000002485 urinary effect Effects 0.000 description 4
- 238000001291 vacuum drying Methods 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 238000009739 binding Methods 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229920009441 perflouroethylene propylene Polymers 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 208000032840 Catheter-Related Infections Diseases 0.000 description 2
- 239000004954 Polyphthalamide Substances 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 229920000840 ethylene tetrafluoroethylene copolymer Polymers 0.000 description 2
- 229920001903 high density polyethylene Polymers 0.000 description 2
- 239000004700 high-density polyethylene Substances 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000004816 latex Substances 0.000 description 2
- 229920000126 latex Polymers 0.000 description 2
- 239000010687 lubricating oil Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 230000010355 oscillation Effects 0.000 description 2
- 229920000139 polyethylene terephthalate Polymers 0.000 description 2
- 239000005020 polyethylene terephthalate Substances 0.000 description 2
- 229920006375 polyphtalamide Polymers 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 229920002379 silicone rubber Polymers 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000007480 spreading Effects 0.000 description 2
- 238000003892 spreading Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 239000004812 Fluorinated ethylene propylene Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 229920002614 Polyether block amide Polymers 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- SWLVFNYSXGMGBS-UHFFFAOYSA-N ammonium bromide Chemical compound [NH4+].[Br-] SWLVFNYSXGMGBS-UHFFFAOYSA-N 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000005660 hydrophilic surface Effects 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229920001684 low density polyethylene Polymers 0.000 description 1
- 239000004702 low-density polyethylene Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 230000010399 physical interaction Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 238000009832 plasma treatment Methods 0.000 description 1
- 210000004623 platelet-rich plasma Anatomy 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920006254 polymer film Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical group 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 238000011076 safety test Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000010301 surface-oxidation reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003512 tertiary amines Chemical group 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 239000012815 thermoplastic material Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
- A61L29/085—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
- A61L2300/208—Quaternary ammonium compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/02—Methods for coating medical devices
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/06—Coatings containing a mixture of two or more compounds
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明提供了一种粘附力增强的润滑涂层，包括底层涂层和表涂涂层；所述底层涂层的原料包括光引发型阴阳离子复合物和溶剂；所述光引发型阴阳离子复合物包括光引发型阳离子物质和阴离子物质；所述表涂涂层的原料包括亲水性单体、亲水性聚合物和溶剂。本发明底涂层中，在固化后，可固化聚合物和粘合促进剂可以物理方式互相结合或以包埋方式形成一个互穿聚合物网络结构。底涂层也可以与表层形成共价键，以构成起稳定的网络涂层。本发明可以实现底涂层在基体材料表面的化学键固定以及内部的自身交联，提高底涂层对基底材料粘附性，提高涂层自身强度，耐磨擦和耐剪切性能。另外，本发明所述底层涂层具有长效抗细菌感染效果。
The invention provides a lubricating coating with enhanced adhesion, comprising a primer coating and a surface coating; the raw materials of the primer coating include a photo-initiated anion-cation complex and a solvent; the photo-initiated anion-cation compound The complex includes a photo-initiated cationic substance and an anionic substance; the raw materials of the surface coating layer include a hydrophilic monomer, a hydrophilic polymer and a solvent. In the primer layer of the present invention, after curing, the curable polymer and the adhesion promoter can be physically bonded to each other or embedded to form an interpenetrating polymer network structure. The primer layer can also form covalent bonds with the surface layer to form a stable network coating. The invention can realize chemical bond fixation of the primer layer on the surface of the base material and internal self-crosslinking, improve the adhesion of the primer layer to the base material, and improve the strength, abrasion resistance and shear resistance of the coating itself. In addition, the primer coating of the present invention has a long-lasting anti-bacterial infection effect.
Description
技术领域technical field
本发明涉及生物材料技术领域，尤其是涉及一种粘附力增强的润滑涂层、其应用和一种医用介入类导管。The invention relates to the technical field of biological materials, in particular to a lubricating coating with enhanced adhesion, its application and a medical interventional catheter.
背景技术Background technique
介入类医用导管多采用高分子材料制成，表面能较低、疏水性强且摩擦系数大，在介入人体过程中容易与粘膜、腔道(尤其是血管)和组织产生较大的摩擦，引起腔道粘膜损伤甚至血管壁破裂。为解决导管使用过程中摩擦力过大的问题，可通过在其表面制备亲水润滑涂层，减小穿插过程的摩擦阻力，减轻对粘膜、血管壁的损伤，缓解病人疼痛感，提高使用安全性。Interventional medical catheters are mostly made of polymer materials, with low surface energy, strong hydrophobicity and large friction coefficient, which are prone to large friction with mucous membranes, cavities (especially blood vessels) and tissues during intervention in the human body, causing Lumen mucosal damage or even vessel wall rupture. In order to solve the problem of excessive friction during the use of the catheter, a hydrophilic lubricating coating can be prepared on the surface of the catheter to reduce the frictional resistance during the insertion process, reduce the damage to the mucous membrane and the blood vessel wall, relieve the pain of the patient, and improve the safety of use. sex.
在导管基底材料表面涂覆一层高附着力的亲水涂层，是提高介入类导管润滑性、降低摩擦力的有效手段。然而，介入类医用导管高分子基底材料种类丰富，包括但不限于聚氯乙烯(PVC)、聚氨酯(TPU)、聚乙烯(PE)、聚丙烯(PP)、乳胶(Latex)、有机硅橡胶、聚醚嵌段聚酰胺(PEBAX)、聚四氟乙烯(PTFE)、聚全氟乙丙烯(FEP)。不同基底材料表面性质差异大，造成常规涂液很难在不同材料表面形成高粘附力润滑涂层。Coating a layer of high-adhesion hydrophilic coating on the surface of the catheter base material is an effective means to improve the lubricity of interventional catheters and reduce friction. However, there are many types of polymer base materials for interventional medical catheters, including but not limited to polyvinyl chloride (PVC), polyurethane (TPU), polyethylene (PE), polypropylene (PP), latex (Latex), silicone rubber, Polyether block polyamide (PEBAX), polytetrafluoroethylene (PTFE), polyperfluoroethylene propylene (FEP). The surface properties of different substrate materials vary greatly, making it difficult for conventional coating solutions to form high-adhesion lubricating coatings on the surfaces of different materials.
目前，在基材表面涂覆增粘底层再引入亲水润滑表层已经成为获得稳定涂层的优选方案。国际医用涂层液巨头帝斯曼公司(DSM)，在利WO 2007065722、WO 2008/104573、CN101970583和CN102947376中公开了具有底层(又称初级涂层)和亲水性表涂制品的制备方法。该底层包括由聚氨酯类低聚物、聚乙烯基吡咯烷酮(PVP)、小分子光引发剂构成的预涂层，可与表涂层形成了稳定、牢固的亲水润滑涂层。尽管专利中聚氨酯类低聚物具有较好的粘附性，并具有不饱和基团可实现光固化形成交联结构，但该体系中底涂与基底材料的作用力主要以物理吸附为主，容易出现涂层牢固性低的问题。另外，该体系采用的引发剂为小分子光引发剂，固化后存在易迁移现象，降低涂层的生物学安全性。At present, coating a tackifying primer on the surface of the substrate and then introducing a hydrophilic lubricating surface layer has become the preferred solution to obtain a stable coating. The international medical coating liquid giant DSM (DSM), in WO 2007065722, WO 2008/104573, CN101970583 and CN102947376, discloses a preparation method of a product with a bottom layer (also known as a primary coating) and a hydrophilic surface coating. The bottom layer includes a precoat layer composed of polyurethane oligomer, polyvinylpyrrolidone (PVP), and small molecule photoinitiator, which can form a stable and firm hydrophilic lubricating coating with the surface coating. Although the polyurethane oligomer in the patent has good adhesion and has unsaturated groups that can realize photocuring to form a cross-linked structure, the force between the primer and the base material in this system is mainly based on physical adsorption. The problem of low coating firmness is prone to occur. In addition, the initiator used in this system is a small-molecule photoinitiator, which is easy to migrate after curing, which reduces the biological safety of the coating.
新加坡杰美特涂层液公司在专利WO 2016200337和CN 107405430中公开了一种用于基底材料上的增粘涂料配方，此底涂层可直接应用在不同衬底上，实现衬底和润滑功能层之间有强大的粘附力。该配方包括聚合物粘合促进剂、第一单体或聚合物交联剂和光引发剂。该聚合物粘合促进剂是嵌段共聚物，包含了疏水/亲水性聚合物嵌段和/或疏水/亲水官能团，在固化后可固化聚合物和粘合促进剂可以物理方式互相结合或以包埋方式形成一个互穿聚合物网络结构。底涂层(增粘涂层)也可以与顶涂层(润滑涂层)形成共价键，以构成起稳定的网络涂层。该体系涂层粘附力得到提升，但是底涂与基底材料的作用力仍是以物理作用为主，且小分子引发剂问题没有得到解决。Singapore Jemet Coating Liquid Company discloses a tackifying coating formulation for base material in patents WO 2016200337 and CN 107405430, and this base coat can be directly applied on different substrates to achieve substrate and lubricating functions There is strong adhesion between layers. The formulation includes a polymeric adhesion promoter, a first monomer or polymeric crosslinker, and a photoinitiator. The polymeric adhesion promoter is a block copolymer containing hydrophobic/hydrophilic polymer blocks and/or hydrophobic/hydrophilic functional groups, and the curable polymer and the adhesion promoter can be physically combined with each other after curing Or form an interpenetrating polymer network structure by embedding. The base coat (tack coat) can also form covalent bonds with the top coat (lubrication coat) to form a stable network coating. The coating adhesion of the system is improved, but the interaction between the primer and the base material is still mainly based on physical interaction, and the problem of small molecular initiators has not been solved.
专利CN 109954169公开了一种包含新型可光固化聚氨酯的底涂涂料组合物，其主链上含有叔胺基团，侧链具有不饱和双键基团和光敏基团单元，该可光固化聚氨酯分子上含有多个交联位点，可以形成牢固的聚合物膜，有效提高亲水润滑涂层在基材，尤其是低表面能基材上的粘附。尽管该专利解决了光引发剂析出的问题，但是具有如此特殊结构聚氨酯的制备，涉及到复杂的有机合成过程，技术路线长、反应条件要求苛刻，造成实际生产时技术难度大、综合成本高。Patent CN 109954169 discloses a primer coating composition comprising a novel photocurable polyurethane, the main chain contains a tertiary amine group, the side chain has an unsaturated double bond group and a photosensitive group unit, the photocurable polyurethane The molecule contains multiple cross-linking sites, which can form a firm polymer film and effectively improve the adhesion of hydrophilic lubricating coatings on substrates, especially low surface energy substrates. Although this patent solves the problem of photoinitiator precipitation, the preparation of polyurethane with such a special structure involves a complex organic synthesis process, a long technical route and harsh reaction conditions, resulting in high technical difficulty and high overall cost in actual production.
发明内容SUMMARY OF THE INVENTION
有鉴于此，本发明要解决的技术问题在于提供一种粘附力增强的润滑涂层，本发明提供的粘附力增强的润滑涂层自带光敏结构单元，构建简单，解决了小分子光引发剂残留和迁移的问题。In view of this, the technical problem to be solved by the present invention is to provide a lubricating coating with enhanced adhesion. Initiator residue and migration issues.
本发明提供了一种粘附力增强的润滑涂层，包括底层涂层和表涂涂层；The present invention provides a lubricating coating with enhanced adhesion, comprising a primer coating and a surface coating;
所述底层涂层的原料包括光引发型阴阳离子复合物和溶剂；所述光引发型阴阳离子复合物包括光引发型阳离子物质和阴离子物质；The raw materials of the primer layer include a photo-initiated anion-cation complex and a solvent; the photo-initiated anion-cation complex includes a photo-initiated cationic substance and an anionic substance;
所述表涂涂层的原料包括亲水性单体、亲水性聚合物和溶剂。The raw materials of the surface coating layer include hydrophilic monomers, hydrophilic polymers and solvents.
优选的，所述光引发型阳离子物质具有式A结构：Preferably, the photoinitiated cationic substance has the structure of formula A:
R选自
R1和R2独立地选自H或C1～C4烷基；R3选自C8～C12烷基；R 1 and R 2 are independently selected from H or C1-C4 alkyl; R 3 is selected from C8-C12 alkyl;
X-选自Cl-或I-。X- is selected from Cl- or I-.
优选的，底层涂层中：Preferably, in the base coat:
所述光引发型阳离子物质选自N-(4-苯甲酰苄基)-N,N-二甲基十二烷基-1-溴化铵、4-(4-(二乙基氨基)苯甲酰基)-N,N-二乙基-N-辛基苯基碘化铵、N,N-二甲基-N-辛基-9-氧-9H-硫杂蒽-3-溴化铵和N-癸基-N,N-二甲基-9,10-双氧-9,10-二氢蒽-2-氯化铵中的一种或多种；The photo-initiated cationic substance is selected from N-(4-benzoylbenzyl)-N,N-dimethyldodecyl-1-ammonium bromide, 4-(4-(diethylamino) Benzoyl)-N,N-diethyl-N-octylphenylammonium iodide, N,N-dimethyl-N-octyl-9-oxo-9H-thiathene-3-bromide One or more of ammonium and N-decyl-N,N-dimethyl-9,10-dioxy-9,10-dihydroanthracene-2-ammonium chloride;
所述阴离子物质为低分子量肝素、磺达肝素、透明质酸、软骨素、硫酸皮肤素、硫酸角质素中的一种或多种；The anionic substance is one or more of low molecular weight heparin, fondaparinux, hyaluronic acid, chondroitin, dermatan sulfate and keratan sulfate;
所述低分子量肝素包括达肝素、那屈肝素、依诺肝素中的一种或多种，平均分子量3000～5000KD；The low molecular weight heparin includes one or more of dalteparin, nadroparin and enoxaparin, and the average molecular weight is 3000-5000KD;
所述磺达肝素分子量为1700KD；The molecular weight of the fondaparinux is 1700KD;
所述的透明质酸分子量为400000～1000000KD；The molecular weight of the hyaluronic acid is 400000～1000000KD;
所述溶剂为甲醇、乙醇、异丙醇、三氯甲烷、丙酮和二甲亚砜中的一种或多种。The solvent is one or more of methanol, ethanol, isopropanol, chloroform, acetone and dimethyl sulfoxide.
优选的，所述光引发型阳离子物质和阴离子物质的质量为(20～85)：100；Preferably, the mass of the photoinitiated cationic substance and the anionic substance is (20-85): 100;
所述光引发型阴阳离子复合物占底层涂层的质量比为0.02％～25％。The mass ratio of the photo-initiated anion-cation complex to the bottom coating is 0.02% to 25%.
所述亲水性单体、亲水性聚合物的质量比为(0.01～15)：(0.01～25)。The mass ratio of the hydrophilic monomer and the hydrophilic polymer is (0.01-15):(0.01-25).
优选的，表涂涂层中：Preferably, in the topcoat:
所述亲水性单体包括聚乙二醇二丙烯酸酯、二甲基丙烯酸二乙二醇酯、三羟甲基丙烷三丙烯酸酯、三羟甲基丙烷三甲基丙烯酸酯和乙氧基化的三羟甲基丙烷三丙烯酸酯中的一种或多种；所述的乙氧基化的三羟甲基丙烷三丙烯酸酯的乙氧基链接数目大于9；The hydrophilic monomers include polyethylene glycol diacrylate, diethylene glycol dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate and ethoxylated one or more of the trimethylolpropane triacrylate; the number of ethoxy links of the ethoxylated trimethylolpropane triacrylate is greater than 9;
所述的亲水性聚合物选自聚乙烯吡咯烷酮(PVP)、聚乙二醇(PEG)、聚乙烯醇(PVA)、聚丙烯酰胺、聚丙烯酸、聚酰胺、聚醚砜、聚酰亚胺、聚醚酰亚胺和聚酞胺中的一种或多种；The hydrophilic polymer is selected from polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyacrylamide, polyacrylic acid, polyamide, polyethersulfone, polyimide , one or more of polyetherimide and polyphthalamide;
所述溶剂为水、N,N-二甲基甲酰胺、二甲基亚砜、丙酮、乙醇、甲醇和异丙醇中的一种或多种。The solvent is one or more of water, N,N-dimethylformamide, dimethylsulfoxide, acetone, ethanol, methanol and isopropanol.
本发明提供了上述技术方案任一项所述的粘附力增强的润滑涂层在制备医用介入类导管表面涂层中的应用。The present invention provides the application of the lubricating coating with enhanced adhesion according to any one of the above technical solutions in preparing the surface coating of medical interventional catheters.
本发明提供了一种医用介入类导管，涂覆有上述技术方案任一项所述的粘附力增强的润滑涂层。The present invention provides a medical interventional catheter, which is coated with the lubricating coating with enhanced adhesion according to any one of the above technical solutions.
本发明提供了一种涂覆润滑涂层粘附力增强的润滑涂层的医用介入类导管的制备方法，包括：The invention provides a preparation method of a medical interventional catheter coated with a lubricating coating with enhanced adhesion of the lubricating coating, comprising:
A)将光引发型阳离子物质水溶液和阴离子物质水溶液反应，得到阴阳离子复合物；A) react the photo-initiated cationic substance aqueous solution with the anionic substance aqueous solution to obtain an anion-cation complex;
B)将阴阳离子复合物溶于溶剂，得到底层涂层溶液；B) dissolving the anion and cation complexes in a solvent to obtain a bottom coating solution;
C)将底层涂层溶液负载在医用介入类导管上，进行紫外固化处理，得到具有粘附力增强的底层涂层的医用导管；C) load the bottom coating solution on the medical interventional catheter, and carry out ultraviolet curing treatment to obtain the medical catheter with the bottom coating with enhanced adhesion;
D)将亲水性单体溶液与亲水性聚合物溶液混合，负载到具有粘附力增强的底层涂层的医用导管表面，紫外固化处理，得到涂覆润滑涂层粘附力增强的润滑涂层的医用介入类导管。D) The hydrophilic monomer solution is mixed with the hydrophilic polymer solution, loaded onto the surface of the medical catheter with the primer coating with enhanced adhesion, and UV-cured to obtain a lubricating coating with enhanced adhesion of the lubricating coating Coated medical interventional catheters.
优选的，所述步骤A)具体为：光引发型阳离子物质水溶液滴加到阴离子物质水溶液中，沉淀析出，洗涤沉淀，冷冻干燥，得到阴阳离子复合物。Preferably, the step A) is specifically as follows: adding the photo-initiated cationic substance aqueous solution dropwise to the anionic substance aqueous solution, precipitating out, washing the precipitation, and freeze-drying to obtain an anion-cationic compound.
优选的，所述光引发型阳离子物质水溶液中光引发型阳离子物质的浓度为0.1～25g/mL；所述阴离子物质水溶液中阴离子物质的浓度为0.1～50g/mL；所述底层涂层溶液中阴阳离子复合物的浓度为0.02～25g/mL；Preferably, the concentration of the photo-initiated cationic substance in the aqueous solution of the photo-initiated cationic substance is 0.1-25 g/mL; the concentration of the anionic substance in the aqueous solution of the anionic substance is 0.1-50 g/mL; The concentration of anion-cation complex is 0.02～25g/mL;
所述亲水性单体溶液中亲水性单体的质量浓度为0.01％～15％；所述亲水性聚合物溶液中亲水性聚合物的质量浓度为0.01％～25％；The mass concentration of the hydrophilic monomer in the hydrophilic monomer solution is 0.01% to 15%; the mass concentration of the hydrophilic polymer in the hydrophilic polymer solution is 0.01% to 25%;
所述负载的方式选自浸渍、喷雾、旋涂或擦拭。The means of loading is selected from dipping, spraying, spin coating or wiping.
优选的，步骤C)所述紫外固化的主透过波长为150～430nm，紫外固化处理的时间为2～15min；Preferably, the main transmission wavelength of the ultraviolet curing in step C) is 150-430 nm, and the time of the ultraviolet curing treatment is 2-15 min;
所述紫外光的光源为低压汞灯、中压汞灯、高压汞灯和加滤光片中的一种或几种。The light source of the ultraviolet light is one or more of a low pressure mercury lamp, a medium pressure mercury lamp, a high pressure mercury lamp and a filter.
与现有技术相比，本发明提供了一种粘附力增强的润滑涂层，包括底层涂层和表涂涂层；所述底层涂层的原料包括光引发型阴阳离子复合物和溶剂；所述光引发型阴阳离子复合物包括光引发型阳离子物质和阴离子物质；所述表涂涂层的原料包括亲水性单体、亲水性聚合物和溶剂。本发明底涂层(增粘涂层)中，在固化后，可固化聚合物和粘合促进剂可以物理方式互相结合或以包埋方式形成一个互穿聚合物网络结构。底涂层(增粘涂层)也可以与顶涂层(润滑涂层)形成共价键，以构成起稳定的网络涂层。本发明所述光引发型阴阳离子复合物型底层在固化时会发生Norrish II反应和重组反应，实现底涂层在基体材料表面的化学键固定以及涂层内部的自身交联，在有效提高低涂层对基底材料粘附性的同时，还增加了提高涂层自身强度，耐磨擦和耐剪切性能提高。Compared with the prior art, the present invention provides a lubricating coating with enhanced adhesion, comprising a primer coating and a surface coating; the raw materials of the primer coating include a photo-initiated anion-cation complex and a solvent; The photo-initiated anion-cation complex includes a photo-initiated cationic substance and an anionic substance; the raw materials of the surface coating layer include a hydrophilic monomer, a hydrophilic polymer and a solvent. In the primer layer (tack coat) of the present invention, after curing, the curable polymer and the adhesion promoter can be physically bonded to each other or embedded to form an interpenetrating polymer network structure. The base coat (tack coat) can also form covalent bonds with the top coat (lubrication coat) to form a stable network coating. The photo-initiated anion-cation composite type bottom layer of the present invention will undergo Norrish II reaction and recombination reaction during curing, so as to realize the chemical bond fixation of the primer layer on the surface of the base material and the self-crosslinking inside the coating layer. While the adhesion of the layer to the base material is increased, the strength of the coating itself is increased, and the abrasion resistance and shear resistance are improved.
本发明采用的光引发型阳离子物质自身就含有光敏结构单元，无需再添加小分子光引发剂，且光固化后被交联限制在涂层网络中，从根本上就解决了小分子光引发剂在涂层中的残留、迁移等行业共性问题。同时，由于底层配方的光引发型阳离子物质的存在，本发明可以直接引发润滑表涂中亲水性单体的固化，从而在表涂配方中也可以不添加引发剂，这样就完全解决了光引发剂问题，涂层整体的生物安全性得到保证。与现有的单一润滑功能涂层配方相比，本发明涂层中含有的阳离子物质具有高效抗菌性，同时该阳离子物质处于涂层内层、被外层润滑层包被，可回避裸露型抗菌剂在复杂生理条件下被生物分子钝化失效的问题，因此涂层具有长期抗感染性，减少医用导管相关感染的发生，延长医用导管的服役时间。The photoinitiated cationic substance used in the present invention itself contains photosensitive structural units, no need to add a small molecular photoinitiator, and after photocuring, it is cross-linked and restricted in the coating network, which fundamentally solves the problem of small molecular photoinitiator. Common problems in the industry such as residue and migration in the coating. At the same time, due to the existence of the photo-initiated cationic substances in the bottom layer formulation, the present invention can directly initiate the curing of the hydrophilic monomer in the lubricating surface coating, so that no initiator can be added in the surface coating formulation, which completely solves the problem of light Initiator issues, the overall biosafety of the coating is guaranteed. Compared with the existing single-lubricating function coating formulation, the cationic substance contained in the coating of the present invention has high-efficiency antibacterial properties, and at the same time, the cationic substance is located in the inner layer of the coating and is covered by the outer lubricating layer, which can avoid exposed antibacterial properties. Therefore, the coating has long-term resistance to infection, reduces the occurrence of medical catheter-related infections, and prolongs the service time of medical catheters.
附图说明Description of drawings
图1为“一种粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管”涂层构建示意图；Figure 1 is a schematic diagram of the coating construction of "a lubricating coating with enhanced adhesion and a medical interventional catheter with lubricating and antibacterial function";
图2为“普通涂层”构建示意图；Figure 2 is a schematic diagram of the construction of "ordinary coating";
图3为未处理医用介入管表面的血小板形貌照片；Figure 3 is a photo of the platelet morphology on the surface of an untreated medical interventional tube;
图4为本发明实施例得到的具有粘附力增强的润滑涂层医用介入管表面的血小板形貌照片；4 is a photo of the platelet morphology on the surface of the lubricating coating medical interventional tube with enhanced adhesion obtained in the embodiment of the present invention;
图5为未处理医用介入管表面的菌落培养数量照片；Figure 5 is a photo of the number of colonies cultured on the surface of the untreated medical interventional tube;
图6为本发明实施例得到的具有粘附力增强的润滑涂层医用介入管表面的菌落培养数量照片；6 is a photo of the number of colonies cultured on the surface of the lubricating coating medical interventional tube with enhanced adhesion obtained in the embodiment of the present invention;
图7为未处理医用介入管表面的细菌粘附和死亡情况照片；Figure 7 is a photo of bacterial adhesion and death on the surface of untreated medical interventional tubes;
图8为对照组具有润滑表涂涂层和普通底层涂层医用介入管表面的细菌粘附和死亡情况照片；Figure 8 is a photo of bacterial adhesion and death on the surface of the medical interventional tube with lubricating surface coating and common bottom coating in the control group;
图9为本发明实施例得到的具有粘附力增强的润滑涂层医用介入管表面的细菌粘附和死亡情况照片。FIG. 9 is a photograph of bacterial adhesion and death on the surface of a medical interventional tube with a lubricating coating with enhanced adhesion obtained in an embodiment of the present invention.
具体实施方式Detailed ways
本发明提供了一种粘附力增强的润滑涂层、其应用和一种医用介入类导管，本领域技术人员可以借鉴本文内容，适当改进工艺参数实现。特别需要指出的是，所有类似的替换和改动对本领域技术人员来说是显而易见的，它们都属于本发明保护的范围。本发明的方法及应用已经通过较佳实施例进行了描述，相关人员明显能在不脱离本发明内容、精神和范围内对本文的方法和应用进行改动或适当变更与组合，来实现和应用本发明技术。The present invention provides a lubricating coating with enhanced adhesion, its application, and a medical interventional catheter, which can be achieved by those skilled in the art by appropriately improving the process parameters for reference. It should be particularly pointed out that all similar replacements and modifications are obvious to those skilled in the art, and they all belong to the protection scope of the present invention. The method and application of the present invention have been described through the preferred embodiments, and it is obvious that relevant persons can make changes or appropriate changes and combinations of the methods and applications herein without departing from the content, spirit and scope of the present invention to realize and apply the present invention. Invention technology.
本发明提供了一种粘附力增强的润滑涂层，包括底层涂层和表涂涂层；The present invention provides a lubricating coating with enhanced adhesion, comprising a primer coating and a surface coating;
所述底层涂层的原料包括光引发型阴阳离子复合物和溶剂；所述光引发型阴阳离子复合物包括光引发型阳离子物质和阴离子物质；The raw materials of the primer layer include a photo-initiated anion-cation complex and a solvent; the photo-initiated anion-cation complex includes a photo-initiated cationic substance and an anionic substance;
所述表涂涂层的原料包括亲水性单体、亲水性聚合物和溶剂。The raw materials of the surface coating layer include hydrophilic monomers, hydrophilic polymers and solvents.
本发明所述表涂涂层有润滑功能，能够抗细菌粘附。The surface coating of the present invention has a lubricating function and can resist bacterial adhesion.
本发明提供的一种粘附力增强的润滑涂层，包括底层涂层。The present invention provides a lubricating coating with enhanced adhesion, comprising a primer coating.
本发明所述底层涂层的原料包括光引发型阴阳离子复合物和溶剂；所述光引发型阴阳离子复合物包括光引发型阳离子物质和阴离子物质；The raw materials of the bottom coating layer of the present invention include a photo-initiated anion-cation complex and a solvent; the photo-initiated anion-cation complex includes a photo-initiated cationic substance and an anion substance;
本发明所述底层涂层具有季铵盐结构的阳离子杀菌功能，可与表涂涂层的抗粘附功能进行协同作用，提高抗细菌感染效果。由于阳离子物质处于涂层内层、被外层润滑层包被，可回避裸露型抗菌剂在复杂生理条件下被生物分子钝化失效的问题，因此涂层具有长期抗感染性。The bottom coating of the invention has the cationic sterilization function of the quaternary ammonium salt structure, and can synergize with the anti-adhesion function of the surface coating to improve the anti-bacterial infection effect. Since the cationic substance is in the inner layer of the coating and is covered by the outer lubricating layer, the problem of the exposed antibacterial agent being passivated and failing by biomolecules under complex physiological conditions can be avoided, so the coating has long-term anti-infective properties.
本发明光引发型阳离子物质具有杀菌性；光引发型阳离子物质自身含有光敏结构单元；底层涂层通过光固化后以化学键固定在基底材料表面；底层涂层通过光固化方式实现涂层内部交联。本发明整个双层结构涂层具有粘附力增强的效果，具有润滑和抗菌功能。The photo-initiated cationic substance of the present invention has bactericidal properties; the photo-initiated cationic substance itself contains a photosensitive structural unit; the underlying coating is fixed on the surface of the base material with chemical bonds after photocuring; . The entire double-layer structural coating of the present invention has the effect of enhancing adhesion, and has lubricating and antibacterial functions.
按照本发明，所述光引发型阳离子物质具有式A结构：According to the present invention, the photoinitiated cationic substance has the structure of formula A:
R选自
R1和R2独立地选自H或C1～C4烷基；R3选自C8～C12烷基；R 1 and R 2 are independently selected from H or C1-C4 alkyl; R 3 is selected from C8-C12 alkyl;
X-选自Cl-或I-。X- is selected from Cl- or I-.
本发明所述光引发型阳离子物质优选选自N-(4-苯甲酰苄基)-N,N-二甲基十二烷基-1-溴化铵、4-(4-(二乙基氨基)苯甲酰基)-N,N-二乙基-N-辛基苯基碘化铵、N,N-二甲基-N-辛基-9-氧-9H-硫杂蒽-3-溴化铵和N-癸基-N,N-二甲基-9,10-双氧-9,10-二氢蒽-2-氯化铵中的一种或多种。The photo-initiated cationic substance of the present invention is preferably selected from N-(4-benzoylbenzyl)-N,N-dimethyldodecyl-1-ammonium bromide, 4-(4-(diethyl) amino)benzoyl)-N,N-diethyl-N-octylphenylammonium iodide, N,N-dimethyl-N-octyl-9-oxo-9H-thiathene-3 - one or more of ammonium bromide and N-decyl-N,N-dimethyl-9,10-dioxo-9,10-dihydroanthracene-2-ammonium chloride.
本发明所述阴离子物质为低分子量肝素、磺达肝素、透明质酸、软骨素、硫酸皮肤素、硫酸角质素中的一种或多种；The anionic substance of the present invention is one or more of low molecular weight heparin, fondaparinux, hyaluronic acid, chondroitin, dermatan sulfate and keratan sulfate;
具体的，所述低分子量肝素包括达肝素、那屈肝素、依诺肝素中的一种或多种，平均分子量3000～5000KD；所述磺达肝素分子量为1700KD；所述的透明质酸分子量为400000～1000000KD；Specifically, the low molecular weight heparin includes one or more of dalteparin, nadroparin and enoxaparin, and the average molecular weight is 3000-5000KD; the molecular weight of the fondaparinux is 1700KD; the molecular weight of the hyaluronic acid is 400000～1000000KD;
本发明底层涂层中，所述溶剂优选为甲醇、乙醇、异丙醇、三氯甲烷、丙酮和二甲亚砜中的一种或多种。In the primer layer of the present invention, the solvent is preferably one or more of methanol, ethanol, isopropanol, chloroform, acetone and dimethyl sulfoxide.
本发明所述光引发型阳离子物质具有杀菌性；其自身含有光敏结构单元；所述底层涂层通过光固化后以化学键固定在基底材料表面；所述底层涂层通过光固化方式实现涂层内部交联。The photo-initiated cationic substance of the present invention has bactericidal properties; it itself contains a photosensitive structural unit; the bottom coating is fixed on the surface of the base material by chemical bonds after photocuring; the bottom coating is photocured to realize the interior of the coating cross-linked.
本发明所述光引发型阳离子物质和阴离子物质的质量优选为(20～85)：100。The mass of the photoinitiated cationic substance and the anionic substance of the present invention is preferably (20-85):100.
本发明所述光引发型阴阳离子复合物占底层涂层的质量比为0.02％～25％。The mass ratio of the photo-initiated anion-cation complex in the base coating is 0.02% to 25%.
本发明提供的一种粘附力增强的润滑涂层，包括表涂涂层。所述表涂涂层的原料包括亲水性单体、亲水性聚合物和溶剂。The present invention provides a lubricating coating with enhanced adhesion, including a topcoat. The raw materials of the surface coating layer include hydrophilic monomers, hydrophilic polymers and solvents.
本发明所述表涂涂层具体良好的润滑性能。The topcoats described in the present invention have particularly good lubricating properties.
按照本发明，所述亲水性单体、亲水性聚合物的质量比优选为(0.01～15)：(0.01～25)。According to the present invention, the mass ratio of the hydrophilic monomer and the hydrophilic polymer is preferably (0.01-15):(0.01-25).
具体的，所述亲水性单体包括聚乙二醇二丙烯酸酯、二甲基丙烯酸二乙二醇酯、三羟甲基丙烷三丙烯酸酯、三羟甲基丙烷三甲基丙烯酸酯和乙氧基化的三羟甲基丙烷三丙烯酸酯中的一种或多种；所述的乙氧基化的三羟甲基丙烷三丙烯酸酯的乙氧基链接数目大于9。Specifically, the hydrophilic monomers include polyethylene glycol diacrylate, diethylene glycol dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate and ethylene glycol One or more of oxygenated trimethylolpropane triacrylates; the ethoxylated trimethylolpropane triacrylates have a number of ethoxy linkages greater than 9.
所述的亲水性聚合物选自聚乙烯吡咯烷酮(PVP)、聚乙二醇(PEG)、聚乙烯醇(PVA)、聚丙烯酰胺、聚丙烯酸、聚酰胺、聚醚砜、聚酰亚胺、聚醚酰亚胺和聚酞胺中的一种或多种；The hydrophilic polymer is selected from polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyacrylamide, polyacrylic acid, polyamide, polyethersulfone, polyimide , one or more of polyetherimide and polyphthalamide;
所述溶剂为水、N,N-二甲基甲酰胺、二甲基亚砜、丙酮、乙醇、甲醇和异丙醇中的一种或多种。The solvent is one or more of water, N,N-dimethylformamide, dimethylsulfoxide, acetone, ethanol, methanol and isopropanol.
本发明所述亲水性单体通过光引发型阳离子物质提供的光敏结构单元实现交联固定。The hydrophilic monomer of the present invention realizes cross-linking and immobilization through the photosensitive structural unit provided by the photo-initiated cationic substance.
本发明提供了上述技术方案任一项所述的粘附力增强的润滑涂层在制备医用介入类导管表面涂层中的应用。The present invention provides the application of the lubricating coating with enhanced adhesion according to any one of the above technical solutions in preparing the surface coating of medical interventional catheters.
本发明对于所述医用介入类导管不进行限定，本领域技术人员熟知的即可，包括但不限于球囊导管、造影导管、微导管、中心静脉导管和留置针套管等。The medical interventional catheter is not limited in the present invention, and those skilled in the art are well-known, including but not limited to balloon catheter, angiography catheter, microcatheter, central venous catheter, indwelling needle cannula, and the like.
本发明所述粘附力增强的润滑涂层可以涂覆于医用介入类导管表面，可以解决导管使用过程中摩擦力过大的问题。The lubricating coating with enhanced adhesion of the present invention can be coated on the surface of a medical interventional catheter, which can solve the problem of excessive friction during the use of the catheter.
本发明的润滑涂料可包括一个底涂层(增粘涂层)和一个顶涂层(润滑涂层)。所述底涂层由固化一个增粘涂料配方所形成，所述增粘涂料配方包括--。在所述底涂层(增粘涂层)中，在固化后，可固化聚合物和粘合促进剂可以物理方式互相结合或以包埋方式形成一个互穿聚合物网络结构。底涂层(增粘涂层)也可以与顶涂层(润滑涂层)形成共价键，以构成起稳定的网络涂层。The lubricious coatings of the present invention may include a base coat (tack coat) and a top coat (lubrication coat). The base coat is formed by curing a tackifying coating formulation comprising -. In the base coat (tack coat), after curing, the curable polymer and the adhesion promoter can be physically bonded to each other or embedded to form an interpenetrating polymer network structure. The base coat (tack coat) can also form covalent bonds with the top coat (lubrication coat) to form a stable network coating.
所述功能或润滑涂层为复合涂层提供润滑性，所述增粘涂层为复合涂层提供稳定性。通过调整亲水性聚合物在增粘涂层中的疏水取代程度，能保证增粘涂层的表面良好地连接到广泛使用的医疗器械材基，例如金属，聚氨酯(PU)、聚氯乙烯(PVC)、橡胶、尼龙、聚丙烯、聚乙烯热塑性材质，聚乙烯(高密度聚乙烯和低密度聚乙烯)，聚全氟乙丙烯(FEP)、聚(乙烯-四氟乙烯)(ETFE)，聚(对苯二甲酸乙二醇酯)(PET)和有机硅弹性体等，其中一些材料疏水性强(表面能低)，例如PP，HDPE，FEP和ETFE，所以要使亲水涂层溶液自发地扩散在这些材料表面上是困难的。不希望被理论所限制，应理解为这个问题的产生是因为这些疏水基底表面能相对所述溶剂(用作所述衬底的表面涂层的一部份的溶剂)的表面能低。这使得很难有效地浸润基底表面。例如，亲水涂层溶液的表面能比所述衬底的表面能高，所以需要以某种方式修改基底表面的表面能。在这种情况下，要实现良好的粘附力的最常用的方法是预处理，如在基底表面进行表面氧化或产生极性基团的等离子体处理。然而，这种预处理润滑涂层可由固化一个可固化亲水聚合物，一个引发剂，和一个溶剂所形成。将可固化亲水聚合物与交联剂或可固化聚合物一同使用的优点：所述可固化亲水聚合物可与交联剂或可固化聚合物自身交联，使整个聚合物网络结构稳定(由于聚合物组分之间的交联)，且所述医疗器械在人体的身体管腔内移动和放置时，微粒的体积可最小化，脱落和迁移作用也较小。The functional or lubricious coating provides lubricity to the composite coating and the tackifying coating provides stability to the composite coating. By adjusting the degree of hydrophobic substitution of hydrophilic polymers in the adhesion-promoting coating, the surface of the adhesion-promoting coating can be well attached to widely used medical device substrates, such as metals, polyurethane (PU), polyvinyl chloride ( PVC), rubber, nylon, polypropylene, polyethylene thermoplastic materials, polyethylene (high density polyethylene and low density polyethylene), polyperfluoroethylene propylene (FEP), poly(ethylene-tetrafluoroethylene) (ETFE), Poly(ethylene terephthalate) (PET) and silicone elastomers, etc. Some of these materials are highly hydrophobic (low surface energy), such as PP, HDPE, FEP and ETFE, so make hydrophilic coating solutions Spontaneous diffusion on the surface of these materials is difficult. Without wishing to be bound by theory, it is understood that this problem arises because the surface energy of these hydrophobic substrates is low relative to the surface energy of the solvent used as part of the surface coating of the substrate. This makes it difficult to effectively wet the substrate surface. For example, the surface energy of a hydrophilic coating solution is higher than that of the substrate, so the surface energy of the substrate surface needs to be modified in some way. In this case, the most common method to achieve good adhesion is pretreatment, such as surface oxidation or plasma treatment to generate polar groups on the substrate surface. However, the pretreatment lubricity coating can be formed by curing a curable hydrophilic polymer, an initiator, and a solvent. Advantages of using a curable hydrophilic polymer with a cross-linking agent or curable polymer: The curable hydrophilic polymer can be cross-linked with the cross-linking agent or the curable polymer itself, stabilizing the entire polymer network structure (due to the cross-linking between the polymer components), and the medical device is moved and placed in the body lumen of the human body, the volume of the particles can be minimized, and the shedding and migration effects are also less.
本发明提供了一种医用介入类导管，涂覆有上述技术方案任一项所述的粘附力增强的润滑涂层。The present invention provides a medical interventional catheter, which is coated with the lubricating coating with enhanced adhesion according to any one of the above technical solutions.
上述为具有润滑抗菌功能的医用介入类导管。The above is a medical interventional catheter with lubricating and antibacterial function.
本发明所述上述技术方案任一项所述的粘附力增强的润滑涂层上述已经有了清楚的描述，在此不再赘述。The lubricating coating with enhanced adhesion according to any one of the above technical solutions of the present invention has been clearly described above, and will not be repeated here.
本发明提供了一种涂覆润滑涂层粘附力增强的润滑涂层的医用介入类导管的制备方法，包括：The invention provides a preparation method of a medical interventional catheter coated with a lubricating coating with enhanced adhesion of the lubricating coating, comprising:
A)将光引发型阳离子物质水溶液和阴离子物质水溶液反应，得到阴阳离子复合物；A) react the photo-initiated cationic substance aqueous solution with the anionic substance aqueous solution to obtain an anion-cation complex;
B)将阴阳离子复合物溶于溶剂，得到底层涂层溶液；B) dissolving the anion and cation complexes in a solvent to obtain a bottom coating solution;
C)将底层涂层溶液负载在医用介入类导管上，进行紫外固化处理，得到具有粘附力增强的底层涂层的医用导管；C) load the bottom coating solution on the medical interventional catheter, and carry out ultraviolet curing treatment to obtain the medical catheter with the bottom coating with enhanced adhesion;
D)将亲水性单体溶液与亲水性聚合物溶液混合，负载到具有粘附力增强的底层涂层的医用导管表面，紫外固化处理，得到涂覆润滑涂层粘附力增强的润滑涂层的医用介入类导管。D) The hydrophilic monomer solution is mixed with the hydrophilic polymer solution, loaded onto the surface of the medical catheter with the primer coating with enhanced adhesion, and UV-cured to obtain a lubricating coating with enhanced adhesion of the lubricating coating Coated medical interventional catheters.
本发明提供了一种涂覆润滑涂层粘附力增强的润滑涂层的医用介入类导管的制备方法，包括：将光引发型阳离子物质水溶液和阴离子物质水溶液反应，得到阴阳离子复合物。The invention provides a preparation method of a medical interventional catheter coated with a lubricating coating with enhanced adhesion of the lubricating coating.
本发明所述步骤A)具体为：光引发型阳离子物质水溶液滴加到阴离子物质水溶液中，沉淀析出，洗涤沉淀，冷冻干燥，得到阴阳离子复合物。The step A) of the present invention is specifically as follows: the photo-initiated cationic substance aqueous solution is added dropwise to the anion substance aqueous solution, precipitated, washed and precipitated, and freeze-dried to obtain an anion-cationic compound.
滴加后有大量白色或淡黄色沉淀从溶液中析出，用蒸馏水或超纯水洗涤沉淀物，冷冻干燥后得到阴阳离子复合物。After the dropwise addition, a large amount of white or light yellow precipitates are precipitated from the solution, and the precipitates are washed with distilled water or ultrapure water, and freeze-dried to obtain an anion-cation complex.
本发明对于光引发型阳离子物质和阴离子物质上述已经有了清楚的描述，在此不再赘述。In the present invention, the above-mentioned photo-initiated cationic substances and anionic substances have been clearly described, which will not be repeated here.
按照本发明，所述光引发型阳离子物质水溶液中光引发型阳离子物质的浓度优选为0.1～25g/mL；更优选为1～23g/mL；According to the present invention, the concentration of the photo-initiated cationic substance in the aqueous solution of the photo-initiated cationic substance is preferably 0.1-25 g/mL; more preferably 1-23 g/mL;
所述阴离子物质水溶液中阴离子物质的浓度优选为0.1～50g/mL；更优选为1～48g/mL。The concentration of the anionic substance in the aqueous solution of the anionic substance is preferably 0.1-50 g/mL; more preferably 1-48 g/mL.
将阴阳离子复合物溶于溶剂，得到底层涂层溶液；本发明所述底层涂层溶液中阴阳离子复合物的浓度优选为0.02～25g/mL；更优选为0.1～12g/mL。The anion and cation complexes are dissolved in a solvent to obtain a bottom coating solution; the concentration of the anion and cation complexes in the bottom coating solution of the present invention is preferably 0.02-25 g/mL; more preferably 0.1-12 g/mL.
将底层涂层溶液负载在医用介入类导管上。本发明所述负载的方式选自浸渍、喷雾、旋涂或擦拭。The primer coating solution is loaded on a medical interventional catheter. The method of loading described in the present invention is selected from dipping, spraying, spin coating or wiping.
本发明对于所述医用介入类导管不进行限定，本领域技术人员熟知的即可；可以理解为一些材质不同的医用导管，比如：留置针套管，导尿管之类，材质可能是硅胶、乳胶。The present invention does not limit the medical interventional catheter, and those skilled in the art are familiar with it; it can be understood as some medical catheters with different materials, such as: indwelling needle cannula, urinary catheter and the like, the material may be silica gel, emulsion.
本发明涂层就是涂在上述管上，整根涂也可以，或者涂一半也可以，或者可以选的，涂层质量可以占导管质量的0.2％～25％。The coating of the present invention is to be coated on the above-mentioned pipe, and the whole pipe can be coated, or half of the pipe can be coated, or alternatively, the quality of the coating can account for 0.2% to 25% of the quality of the pipe.
而后进行紫外固化处理，得到具有粘附力增强的底层涂层的医用导管。Then, ultraviolet curing treatment is performed to obtain a medical catheter with a primer coating with enhanced adhesion.
得到的附着有阴阳离子复合物涂层的导管后，本发明将所述附着有复合物的导管进行紫外固化处理，得到粘附力增强的具有交联结构的底层涂层的导管。After obtaining the catheter with an anion-cation composite coating attached, the present invention performs ultraviolet curing treatment on the composite-attached catheter to obtain a catheter with a cross-linked structure and a primer coating with enhanced adhesion.
在本发明中，所述紫外光的光源优选为低压汞灯、中压汞灯、高压汞灯和加滤光片中的一种或几种。所述紫外固化处理采用的紫外光的主透过波长优选为150～430nm，更优选为200～380nm；所述紫外固化处理的时间优选为2～15min，更优选为3～8min。In the present invention, the light source of the ultraviolet light is preferably one or more of a low pressure mercury lamp, a medium pressure mercury lamp, a high pressure mercury lamp and a filter. The main transmission wavelength of the ultraviolet light used in the ultraviolet curing treatment is preferably 150-430 nm, more preferably 200-380 nm; the time of the ultraviolet curing treatment is preferably 2-15 minutes, more preferably 3-8 minutes.
紫外固化处理后，本发明优选将紫外固化处理产物依次进行清洗和干燥。所述清洗条件包括水浴、水浴震荡和超声清洗，本发明优选在水浴振荡的条件下，依次采用乙醇和去离子水进行清洗，得到清洗后的涂层。在本发明中，所述水浴振荡的频率优选为100～200Hz，更优选为120～150Hz；所述乙醇清洗的时间优选为15～60min，更优选为30～40min；所述去离子水清洗的时间优选为10～50min，更优选为25～30min。本发明对所述清洗用的乙醇和去离子水的用量没有特殊的限制。在本发明中，所述干燥优选为真空干燥，所述干燥的时间优选为12～30小时，更优选为24～28小时；所述干燥的温度优选为45～80℃，更优选为60～70℃。After the ultraviolet curing treatment, in the present invention, the ultraviolet curing treatment product is preferably washed and dried in sequence. The cleaning conditions include water bath, water bath shaking and ultrasonic cleaning. In the present invention, preferably, under the condition of water bath shaking, ethanol and deionized water are used for cleaning in sequence to obtain a cleaned coating. In the present invention, the frequency of the water bath oscillation is preferably 100-200 Hz, more preferably 120-150 Hz; the ethanol cleaning time is preferably 15-60 minutes, more preferably 30-40 minutes; the deionized water cleaning The time is preferably 10 to 50 minutes, more preferably 25 to 30 minutes. The present invention has no special restrictions on the amounts of ethanol and deionized water used for cleaning. In the present invention, the drying is preferably vacuum drying, and the drying time is preferably 12-30 hours, more preferably 24-28 hours; the drying temperature is preferably 45-80° C., more preferably 60- 70°C.
将亲水性单体溶液与亲水性聚合物溶液混合，负载到具有粘附力增强的底层涂层的医用导管表面。A hydrophilic monomer solution is mixed with a hydrophilic polymer solution and loaded onto the surface of a medical catheter with an adhesion-enhancing primer coating.
本发明所述亲水性单体溶液中的溶剂优选为水、N,N-二甲基甲酰胺、二甲基亚砜、丙酮、乙醇、甲醇和异丙醇中的一种或多种。The solvent in the hydrophilic monomer solution of the present invention is preferably one or more of water, N,N-dimethylformamide, dimethylsulfoxide, acetone, ethanol, methanol and isopropanol.
本发明所述亲水性单体溶液中亲水性单体的质量浓度为0.01％～15％；更优选为0.1～10g/mL。所述亲水性聚合物溶液中亲水性聚合物的质量浓度为0.01％～25％；更优选为1～15g/mL。The mass concentration of the hydrophilic monomer in the hydrophilic monomer solution of the present invention is 0.01% to 15%; more preferably, it is 0.1 to 10 g/mL. The mass concentration of the hydrophilic polymer in the hydrophilic polymer solution is 0.01% to 25%; more preferably, it is 1 to 15 g/mL.
而后进行紫外固化处理，得到涂覆润滑涂层粘附力增强的润滑涂层的医用介入类导管。Then, ultraviolet curing treatment is performed to obtain a medical interventional catheter coated with a lubricating coating with enhanced adhesion of the lubricating coating.
所述紫外固化处理采用的紫外光的主透过波长优选为150～430nm，更优选为200～380nm；所述紫外固化处理的时间优选为2～15min，更优选为3～8min。The main transmission wavelength of the ultraviolet light used in the ultraviolet curing treatment is preferably 150-430 nm, more preferably 200-380 nm; the time of the ultraviolet curing treatment is preferably 2-15 minutes, more preferably 3-8 minutes.
紫外固化处理后，本发明优选将紫外固化处理产物依次进行清洗和干燥。所述清洗条件包括水浴、水浴震荡和超声清洗，本发明优选在水浴振荡的条件下，依次采用乙醇和去离子水进行清洗，得到清洗后的涂层。在本发明中，所述水浴振荡的频率优选为100～200Hz，更优选为120～150Hz；所述乙醇清洗的时间优选为15～60min，更优选为30～40min；所述去离子水清洗的时间优选为10～50min，更优选为25～30min。本发明对所述清洗用的乙醇和去离子水的用量没有特殊的限制。在本发明中，所述干燥优选为真空干燥，所述干燥的时间优选为12～30小时，更优选为24～28小时；所述干燥的温度优选为45～80℃，更优选为60～70℃。After the ultraviolet curing treatment, in the present invention, the ultraviolet curing treatment product is preferably washed and dried in sequence. The cleaning conditions include water bath, water bath shaking and ultrasonic cleaning. In the present invention, preferably, under the condition of water bath shaking, ethanol and deionized water are used for cleaning in sequence to obtain a cleaned coating. In the present invention, the frequency of the water bath oscillation is preferably 100-200 Hz, more preferably 120-150 Hz; the ethanol cleaning time is preferably 15-60 minutes, more preferably 30-40 minutes; the deionized water cleaning The time is preferably 10 to 50 minutes, more preferably 25 to 30 minutes. The present invention has no special restrictions on the amounts of ethanol and deionized water used for cleaning. In the present invention, the drying is preferably vacuum drying, and the drying time is preferably 12-30 hours, more preferably 24-28 hours; the drying temperature is preferably 45-80° C., more preferably 60- 70°C.
本发明提供了一种粘附力增强的润滑涂层，包括底层涂层和表涂涂层；所述底层涂层的原料包括光引发型阴阳离子复合物和溶剂；所述光引发型阴阳离子复合物包括光引发型阳离子物质和阴离子物质；所述表涂涂层的原料包括亲水性单体、亲水性聚合物和溶剂。本发明底涂层(增粘涂层)中，在固化后，可固化聚合物和粘合促进剂可以物理方式互相结合或以包埋方式形成一个互穿聚合物网络结构。底涂层(增粘涂层)也可以与顶涂层(润滑涂层)形成共价键，以构成起稳定的网络涂层。本发明所述光引发型阴阳离子复合物型底层在固化时会发生Norrish II反应和重组反应，实现底涂层在基体材料表面的化学键固定以及涂层内部的自身交联，在有效提高低涂层对基底材料粘附性的同时，还增加了提高涂层自身强度，耐磨擦和耐剪切性能提高。The invention provides a lubricating coating with enhanced adhesion, including a primer coating and a surface coating; the raw materials of the primer coating include a photo-initiated anion-cation complex and a solvent; the photo-initiated anion-cation compound The complex includes a photo-initiated cationic substance and an anionic substance; the raw materials of the surface coating layer include a hydrophilic monomer, a hydrophilic polymer and a solvent. In the primer layer (tack coat) of the present invention, after curing, the curable polymer and the adhesion promoter can be physically bonded to each other or embedded to form an interpenetrating polymer network structure. The base coat (tack coat) can also form covalent bonds with the top coat (lubrication coat) to form a stable network coating. The photo-initiated anion-cation composite type bottom layer of the present invention will undergo Norrish II reaction and recombination reaction during curing, so as to realize the chemical bond fixation of the primer layer on the surface of the base material and the self-crosslinking inside the coating layer. While the adhesion of the layer to the base material is increased, the strength of the coating itself is increased, and the abrasion resistance and shear resistance are improved.
本发明采用的光引发型阳离子物质自身就含有光敏结构单元，无需再添加小分子光引发剂，且光固化后被交联限制在涂层网络中，从根本上就解决了小分子光引发剂在涂层中的残留、迁移等行业共性问题。同时，由于底层配方的光引发型阳离子物质的存在，本发明可以直接引发润滑表涂中亲水性单体的固化，从而在表涂配方中也可以不添加引发剂，这样就完全解决了光引发剂问题，涂层整体的生物安全性得到保证。与现有的单一润滑功能涂层配方相比，本发明涂层中含有的阳离子物质具有高效抗菌性，同时该阳离子物质处于涂层内层、被外层润滑层包被，可回避裸露型抗菌剂在复杂生理条件下被生物分子钝化失效的问题，因此涂层具有长期抗感染性，减少医用导管相关感染的发生，延长医用导管的服役时间。The photoinitiated cationic substance used in the present invention itself contains photosensitive structural units, no need to add a small molecular photoinitiator, and after photocuring, it is cross-linked and restricted in the coating network, which fundamentally solves the problem of small molecular photoinitiator. Common problems in the industry such as residue and migration in the coating. At the same time, due to the existence of the photo-initiated cationic substances in the bottom layer formulation, the present invention can directly initiate the curing of the hydrophilic monomer in the lubricating surface coating, so that no initiator can be added in the surface coating formulation, which completely solves the problem of light Initiator issues, the overall biosafety of the coating is guaranteed. Compared with the existing single-lubricating function coating formulation, the cationic substance contained in the coating of the present invention has high-efficiency antibacterial properties, and at the same time, the cationic substance is located in the inner layer of the coating and is covered by the outer lubricating layer, which can avoid exposed antibacterial properties. Therefore, the coating has long-term resistance to infection, reduces the occurrence of medical catheter-related infections, and prolongs the service time of medical catheters.
为了进一步说明本发明，以下结合实施例对本发明提供的一种粘附力增强的润滑涂层、其应用和一种医用介入类导管进行详细描述。In order to further illustrate the present invention, a lubricating coating with enhanced adhesion provided by the present invention, its application and a medical interventional catheter are described in detail below with reference to the examples.
实施例1Example 1
A)配制浓度为0.8g/mL的N-(4-苯甲酰苄基)-N的水溶液，配制浓度为1.5g/mL的肝素钠溶液；将上述N-(4-苯甲酰苄基)-N的水溶液逐滴滴加到10ml的肝素钠溶液中，直至溶液中析出大量白色沉淀，静置2h后，过滤得到白色沉淀物。用超纯水洗涤沉淀物3次，冷冻干燥后得到阴阳离子复合物。A) Prepare an aqueous solution of N-(4-benzoylbenzyl)-N with a concentration of 0.8 g/mL, and prepare a sodium heparin solution with a concentration of 1.5 g/mL; the above N-(4-benzoylbenzyl) The aqueous solution of )-N was added dropwise to 10 ml of sodium heparin solution until a large amount of white precipitate was precipitated in the solution. After standing for 2 h, the white precipitate was obtained by filtration. The precipitate was washed three times with ultrapure water and freeze-dried to obtain an anion-cation complex.
B)将所述步骤A)得到的阴阳离子复合物溶于乙醇溶液中，制备浓度为8g/mL的阴阳离子复合物溶液；将聚氨酯中心静脉导管(重量为X0)在上述复合物溶液中浸泡45min，在25℃放置使乙醇溶剂完全挥发，得到物理吸附阴阳离子复合物的涂层的中心静脉导管(重量为X1)。B) Dissolving the anion-cation complex obtained in step A) in an ethanol solution to prepare an anion-cation complex solution with a concentration of 8 g/mL; soak the polyurethane central venous catheter (weight X0) in the above-mentioned complex solution For 45 minutes, the ethanol solvent was placed at 25° C. to completely volatilize to obtain a central venous catheter (weight X1) coated with a physical adsorption anion-cation complex.
C)将负载有复合物的中心静脉导管至于波长为365nm、功率为320W的高压汞灯下照射5min，N-(4-苯甲酰苄基)-N在紫外激发下与肝素钠和基底发生结合反应，在中心静脉导管表面得到粘附力增强的具有交联结构的底层涂层。随后将中心静脉导管在150Hz的水浴超声条件下，先后用乙醇、去离子水各清洗3次，每次8min；然后在60℃，真空干燥24h后得到模量适中的具有交联结构的涂层的中心静脉导管((重量为X2)。C) The central venous catheter loaded with the complex was irradiated under a high-pressure mercury lamp with a wavelength of 365 nm and a power of 320 W for 5 min, and N-(4-benzoylbenzyl)-N reacted with sodium heparin and substrate under ultraviolet excitation. Combined with the reaction, a primer coating with a cross-linked structure with enhanced adhesion is obtained on the surface of the central venous catheter. Then, the central venous catheter was washed with ethanol and deionized water for 3 times under the ultrasonic condition of 150 Hz water bath, each time for 8 min; then, after vacuum drying at 60 °C for 24 h, a coating with a moderate modulus and a cross-linked structure was obtained The central venous catheter ((weight is X2).
D)配制浓度为0.2g/mL的聚乙二醇水溶液，配制浓度为1g/mL二甲基丙烯酸二乙二醇酯溶液，将上述溶液混合后，浸涂到固定有增粘底层的中心静脉导管表面，用波长为365nm、功率为330W的高压汞灯照射8min，随后用乙醇、去离子水超声振荡洗涤，得到具有润滑表涂涂层和粘附力增强的底层涂层的双层涂层结构的中心静脉导管(重量为X3)。D) Prepare an aqueous solution of polyethylene glycol with a concentration of 0.2 g/mL, and prepare a solution of diethylene glycol dimethacrylate with a concentration of 1 g/mL. After mixing the above solutions, dip-coat it on the central vein fixed with the tackifying bottom layer The surface of the catheter was irradiated with a high-pressure mercury lamp with a wavelength of 365 nm and a power of 330 W for 8 min, followed by ultrasonic washing with ethanol and deionized water to obtain a double-layer coating with a lubricating topcoat and an adhesion-enhancing primer coat Structural central venous catheter (weight X3).
实施例2Example 2
A)配制浓度为3g/mL-的N-二乙基-N-辛基苯基碘化铵的丙酮溶液，配制浓度为12g/mL的透明质酸钠水溶液；将上述N-二乙基-N-辛基苯基碘化铵的水溶液逐滴滴加到25ml的透明质酸钠溶液中，直至溶液中析出大量白色沉淀，静置3.5h后，过滤得到白色沉淀物。用超纯水洗涤沉淀物3次，冷冻干燥后得到阴阳离子复合物。A) prepare an acetone solution of N-diethyl-N-octylphenylammonium iodide with a concentration of 3 g/mL, and prepare an aqueous sodium hyaluronate solution with a concentration of 12 g/mL; The aqueous solution of N-octylphenylammonium iodide was added dropwise to 25 ml of sodium hyaluronate solution, until a large amount of white precipitate was precipitated in the solution, and after standing for 3.5 hours, the white precipitate was obtained by filtration. The precipitate was washed three times with ultrapure water and freeze-dried to obtain an anion-cation complex.
B)将所述步骤A)得到的阴阳离子复合物溶于丙酮溶液中，制备浓度为12g/mL的阴阳离子复合物溶液；将聚氨酯静脉留置针套管(重量为X0)在上述复合物溶液中浸泡60min，在25℃放置使丙酮溶剂完全挥发，得到物理吸附阴阳离子复合物的涂层的静脉留置针套管(重量为X1)。B) Dissolving the anion and cation complex obtained in the step A) in an acetone solution to prepare an anion and cation complex solution with a concentration of 12 g/mL; place a polyurethane intravenous indwelling needle cannula (weight X0) in the above complex solution Soak for 60 min in 25°C and place at 25° C. to completely volatilize the acetone solvent to obtain an intravenous indwelling needle cannula (weight X1) coated with a physical adsorption anion-cation complex.
C)将负载有复合物的静脉留置针套管至于波长为235nm、功率为380W的高压汞灯下照射3min，N-二乙基-N-辛基苯基碘化铵在紫外激发下与透明质酸钠和基底发生结合反应，在静脉留置针套管表面得到粘附力增强的具有交联结构的底层涂层。随后将静脉留置针套管在120Hz的水浴超声条件下，先后用乙醇、去离子水各清洗3次，每次15min；然后在65℃，真空干燥24h后得到模量适中的具有交联结构的涂层的静脉留置针套管(重量为X2)。C) The venous indwelling needle cannula loaded with the complex was irradiated for 3 min under a high-pressure mercury lamp with a wavelength of 235 nm and a power of 380 W, and N-diethyl-N-octylphenylammonium iodide was subjected to ultraviolet excitation with transparent The sodium phosphate reacts with the substrate, and the surface of the intravenous indwelling needle cannula obtains a primer coating with a cross-linked structure with enhanced adhesion. Subsequently, the cannula of the intravenous indwelling needle was washed with ethanol and deionized water for 3 times each for 15 min under the condition of 120 Hz water bath ultrasonic; Coated venous indwelling needle cannula (weight X2).
D)配制浓度为2.5g/mL的聚丙烯酰胺乙醇溶液，配制浓度为1.8g/mL三羟甲基丙烷三丙烯酸酯溶液，将上述溶液混合后，浸涂到固定有增粘底层的静脉留置针套管表面，用波长为365nm、功率为330W的高压汞灯照射8min，随后用乙醇、去离子水超声振荡洗涤，得到具有润滑表涂涂层和粘附力增强的底层涂层的双层涂层结构的静脉留置针套管(重量为X3)。D) Prepare a polyacrylamide ethanol solution with a concentration of 2.5 g/mL, and prepare a trimethylolpropane triacrylate solution with a concentration of 1.8 g/mL. After mixing the above solutions, dip-coat it on the venous indwelling fixed with the tackifying bottom layer The surface of the needle cannula was irradiated with a high-pressure mercury lamp with a wavelength of 365 nm and a power of 330 W for 8 min, followed by ultrasonic washing with ethanol and deionized water to obtain a double layer with a lubricating surface coating and an adhesion-enhancing primer coating. Venous indwelling needle cannula with coated structure (weight X3).
实施例3Example 3
A)配制浓度为0.5g/mL-的N-二甲基十二烷基-1-溴化铵的乙醇溶液，配制浓度为1.5g/mL的软骨素甲醇溶液；将上述N-二甲基十二烷基-1-溴化铵的水溶液逐滴滴加到5ml的软骨素溶液中，直至溶液中析出大量白色沉淀，静置1.5h后，过滤得到白色沉淀物。用超纯水洗涤沉淀物3次，冷冻干燥后得到阴阳离子复合物。A) Prepare an ethanol solution of N-dimethyldodecyl-1-ammonium bromide with a concentration of 0.5 g/mL, and prepare a chondroitin methanol solution with a concentration of 1.5 g/mL; The aqueous solution of dodecyl-1-ammonium bromide was added dropwise to 5 ml of chondroitin solution until a large amount of white precipitate was precipitated in the solution. After standing for 1.5 hours, the white precipitate was obtained by filtration. The precipitate was washed three times with ultrapure water and freeze-dried to obtain an anion-cation complex.
B)将所述步骤A)得到的阴阳离子复合物溶于甲醇溶液中，制备浓度为0.8g/mL的阴阳离子复合物溶液；将PVC导尿管(重量为X0)在上述复合物溶液中浸泡60min，在25℃放置使甲醇溶剂完全挥发，得到物理吸附阴阳离子复合物的涂层的PVC导尿管(重量为X1)。B) Dissolving the anion and cation complex obtained in step A) in methanol solution to prepare an anion and cation complex solution with a concentration of 0.8 g/mL; put a PVC catheter (weight X0) in the above complex solution Soak for 60 min, place at 25° C. to completely volatilize the methanol solvent, and obtain a PVC urinary catheter (weight X1) coated with a physical adsorption anion-cation complex.
C)将负载有复合物的PVC导尿管至于波长为240nm、功率为200W的中压汞灯下照射8min，N-二甲基十二烷基-1-溴化铵在紫外激发下与软骨素和基底发生结合反应，在PVC导尿管表面得到粘附力增强的具有交联结构的底涂涂层。随后将PVC导尿管在180Hz的水浴超声条件下，先后用乙醇、去离子水各清洗3次，每次20min；然后在50℃，真空干燥24h后得到模量适中的具有交联结构的涂层的PVC导尿管(重量为X2)。C) The PVC catheter loaded with the composite was irradiated under a medium pressure mercury lamp with a wavelength of 240 nm and a power of 200 W for 8 min. The binding reaction occurs between the element and the substrate, and a primer coating with a cross-linked structure with enhanced adhesion is obtained on the surface of the PVC urinary catheter. Subsequently, the PVC catheter was washed with ethanol and deionized water for 3 times under the ultrasonic condition of 180 Hz water bath, each time for 20 min; and then vacuum-dried at 50 °C for 24 h to obtain a coating with a moderate modulus and a cross-linked structure. Layer of PVC catheter (weight X2).
D)配制浓度为0.3g/mL的聚乙烯吡咯烷酮甲醇溶液，配制浓度为1.2g/mL聚乙二醇二丙烯酸酯溶液，将上述溶液混合后，浸涂到固定有增粘底层的静脉留置针套管表面，用波长为246nm、功率为330W的高压汞灯照射3min，随后用乙醇、去离子水超声振荡洗涤，得到具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的PVC导尿管(重量为X3)。D) Prepare a polyvinylpyrrolidone methanol solution with a concentration of 0.3 g/mL, and prepare a polyethylene glycol diacrylate solution with a concentration of 1.2 g/mL. After mixing the above solutions, dip-coat it on the venous indwelling needle fixed with the tackifying bottom layer The surface of the casing was irradiated with a high-pressure mercury lamp with a wavelength of 246 nm and a power of 330 W for 3 min, followed by ultrasonic washing with ethanol and deionized water to obtain a double layer with a lubricating surface coating and an adhesion-enhancing primer coating. Coated PVC catheter (weight X3).
实施例4Example 4
A)配制浓度为1.5g/mL的N-(4-苯甲酰苄基)-N的丙酮溶液，配制浓度为1.5g/mL的透明质酸钠水溶液；将上述N-(4-苯甲酰苄基)-N的水溶液逐滴滴加到8ml的透明质酸钠溶液中，直至溶液中析出大量白色沉淀，静置2h后，过滤得到白色沉淀物。用超纯水洗涤沉淀物3次，冷冻干燥后得到阴阳离子复合物。A) Prepare an acetone solution of N-(4-benzoylbenzyl)-N with a concentration of 1.5 g/mL, and prepare an aqueous sodium hyaluronate solution with a concentration of 1.5 g/mL; The aqueous solution of acylbenzyl)-N was added dropwise to 8 ml of sodium hyaluronate solution until a large amount of white precipitate was precipitated in the solution. After standing for 2 hours, the white precipitate was obtained by filtration. The precipitate was washed three times with ultrapure water and freeze-dried to obtain an anion-cation complex.
B)将所述步骤A)得到的阴阳离子复合物溶于乙醇溶液中，制备浓度为8g/mL的阴阳离子复合物溶液；将聚氨酯静脉留置针套管(重量为X0)在上述复合物溶液中浸泡60min，在25℃放置使乙醇溶剂完全挥发，得到物理吸附阴阳离子复合物的涂层的静脉留置针套管(重量为X1)。B) Dissolving the anion and cation complex obtained in the step A) in an ethanol solution to prepare an anion and cation complex solution with a concentration of 8 g/mL; place a polyurethane intravenous indwelling needle cannula (weight X0) in the above complex solution Soak for 60 minutes in 25°C, and place at 25° C. to completely volatilize the ethanol solvent to obtain a cannula for intravenous indwelling needles (weight X1) coated with a physical adsorption anion-cation complex.
C)将负载有复合物的静脉留置针套管至于波长为365nm、功率为320W的高压汞灯下照射3min，N-(4-苯甲酰苄基)-N在紫外激发下与透明质酸钠和基底发生结合反应，在静脉留置针套管表面得到粘附力增强的具有交联结构的底涂涂层。随后将静脉留置针套管在150Hz的水浴超声条件下，先后用乙醇、去离子水各清洗3次，每次8min；然后在60℃，真空干燥24h后得到模量适中的具有交联结构的涂层的静脉留置针套管((重量为X2)。C) The intravenous indwelling needle cannula loaded with the complex was irradiated for 3 min under a high-pressure mercury lamp with a wavelength of 365 nm and a power of 320 W, and N-(4-benzoylbenzyl)-N reacted with hyaluronic acid under ultraviolet excitation. A binding reaction occurs between sodium and the substrate, and a primer coating with a cross-linked structure with enhanced adhesion is obtained on the surface of the intravenous indwelling needle cannula. Subsequently, the cannula of the intravenous indwelling needle was washed with ethanol and deionized water for 3 times under the ultrasonic condition of 150 Hz in a water bath, each time for 8 min. Coated venous indwelling needle cannula ((weight is X2).
D)配制浓度为3.5g/mL的聚乙烯吡咯烷酮异丙醇溶液，配制浓度为1g/mL二甲基丙烯酸二乙二醇酯溶液，将上述溶液混合后，浸涂到固定有增粘底层的静脉留置针套管，用波长为365nm、功率为330W的高压汞灯照射10min，随后用乙醇、去离子水超声振荡洗涤，得到具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的静脉留置针套管(重量为X3)。D) prepare a polyvinylpyrrolidone isopropanol solution with a concentration of 3.5g/mL, prepare a solution of diethylene glycol dimethacrylate with a concentration of 1g/mL, mix the above solutions, and dip-coat the solution on the surface with the tackifying bottom layer fixed. The venous indwelling needle cannula was irradiated with a high-pressure mercury lamp with a wavelength of 365 nm and a power of 330 W for 10 min, followed by ultrasonic washing with ethanol and deionized water to obtain a lubricating surface coating and a primer coating with enhanced adhesion. Venous indwelling needle cannula with double-layer coating structure (weight X3).
实施例5性能测试Example 5 Performance Test
1)涂层粘附力测试：1) Coating adhesion test:
将实施例1-4制得的负载阴阳离子复合物中间体涂层的医用介入类导管(重量X1)、负载粘附力增强的交联结构的底涂涂层的医用介入类导管(重量X2)和负载润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管(重量X3)和对照组负载普通涂层的医用介入导管(重量Y1)分别在超声波清洗机中处理10min和60min后，在60℃下，真空干燥24h后，称重(重量即为X4、X5、X6和Y2)。计算涂层存留率，对于负载中间体涂层的医用介入类导管其计算公式为：涂层留存率1(％)＝(X4-X0/X1-X0)×100％；对于负载粘附力增强的交联结构的底涂涂层的医用介入类导管其计算公式为：涂层留存率2(％)＝(X5-W0/X2-W0)×100％；对于负载润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管其计算公式为：涂层留存率3(％)＝(X6-W0/X3-W0)×100％；对于对照组负载普通涂层的医用介入导管其计算公式为：涂层留存率4(％)＝(Y2-W0/Y1-W0)×100％。结果如表1所示，表1为本发明实施例1-4得到的具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管的涂层存留率。The medical interventional catheters (weight X1) loaded with an anion-cation complex intermediate coating prepared in Examples 1-4 and the medical interventional catheters loaded with the primer coating of the cross-linked structure with enhanced adhesion (weight X2 ) and the medical interventional catheter (weight X3) and the double-layer coating structure loaded with lubricating surface coating and adhesion-enhancing primer coating and the medical interventional catheter (weight Y1) loaded with ordinary coating in the control group were respectively in After 10min and 60min treatment in an ultrasonic cleaner, vacuum drying at 60°C for 24h, and weighing (the weights are X4, X5, X6 and Y2). Calculate the coating retention rate. For the medical interventional catheter loaded with intermediate coating, the calculation formula is: coating retention rate 1(%)=(X4-X0/X1-X0)×100%; The cross-linked structure of the primer-coated medical interventional catheter, its calculation formula is: coating retention rate 2 (%) = (X5-W0/X2-W0) × 100%; The calculation formula of the medical interventional catheter with the double-layer coating structure of the primer coating with enhanced adhesion is: coating retention rate 3(%)=(X6-W0/X3-W0)×100%; for the load of the control group The calculation formula of the medical interventional catheter with ordinary coating is: coating retention rate 4(%)=(Y2-W0/Y1-W0)×100%. The results are shown in Table 1. Table 1 is the coating retention of the medical interventional catheter with a double-layer coating structure with a lubricating surface coating and an adhesion-enhancing primer coating obtained in Examples 1-4 of the present invention. Rate.
表1本发明实施例1-4得到的具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管的涂层存留率Table 1 Coating retention rate of medical interventional catheters with a double-layer coating structure with a lubricating surface coating and an adhesion-enhancing primer coating obtained in Examples 1-4 of the present invention
由表1可以看出，本发明所述的具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管的涂层存留率在超声10min、60min后分别高达99.5％、98.8％，而仅以物理方式负载的中间体涂层的留置针套管涂层存留率分别为43.2％、26.1％，其中对照组负载普通涂层的医用介入类导管的涂层留存率分别为62.1％、46.4％，说明本发明提供的润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构具有更高的基体附着力和涂层自身的稳定性。As can be seen from Table 1, the coating retention rate of the medical interventional catheter with the double-layer coating structure of the lubricating surface coating and the adhesion-enhancing primer coating of the present invention is after ultrasonic 10min, 60min. As high as 99.5% and 98.8%, respectively, while the coating retention rates of the indwelling needle cannula with the intermediate coating only loaded by physical means were 43.2% and 26.1%, respectively. The layer retention rates are 62.1% and 46.4% respectively, indicating that the double-layer coating structure of the lubricating surface coating and the primer coating with enhanced adhesion provided by the present invention has higher substrate adhesion and stability of the coating itself. sex.
2)涂层润滑性测试1：2) Coating Lubricity Test 1:
本发明采用MXD-02摩擦系数仪对实施例1中具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管(实施例组)、具有相同润滑表涂涂层和普通底涂涂层的双层涂层结构的医用介入类导管(对照组)以及未改性医用介入类导管(未改性组)进行摩擦系数的测试。首先分别将以上3组医用介入类导管超声清洗3次，每次15min，然后固定在凹槽板上，向储水槽注入水直至试样完全浸泡其中。将200g的标准滑块轻放入于试样上方，由传感器连接杆拖动滑块以100mm/min的速度运动，测出动摩擦系数，重复以上步骤，结果如表2-1和2-2所示，表2-1和2-2为粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管的摩擦系数。The present invention adopts the MXD-02 friction coefficient meter to the medical interventional catheter (Example group) with the double-layer coating structure of the lubricating surface coating and the adhesion-enhancing primer coating in Example 1, with the same lubrication The friction coefficient of the medical interventional catheter (control group) with the double-coated structure of the surface coating and the common primer coating and the unmodified medical interventional catheter (unmodified group) were tested. First, the above three groups of medical interventional catheters were ultrasonically cleaned 3 times for 15 minutes each time, and then fixed on the groove plate, and water was injected into the water storage tank until the samples were completely immersed in it. Lightly place the 200g standard slider above the sample, drag the slider by the sensor connecting rod to move at a speed of 100mm/min, measure the coefficient of kinetic friction, repeat the above steps, the results are shown in Tables 2-1 and 2-2 Tables 2-1 and 2-2 are the friction coefficients of the lubricating coatings with enhanced adhesion and their medical interventional catheters with lubricating and antibacterial functions.
表2-1粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管的摩擦系数(第一次清洗)Table 2-1 The friction coefficient of the lubricating coating with enhanced adhesion and the medical interventional catheter with lubricating and antibacterial function (the first cleaning)
表2-2粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管的摩擦系数(第二次清洗)Table 2-2 The friction coefficient of the lubricating coating with enhanced adhesion and the medical interventional catheter with lubricating and antibacterial function (the second cleaning)
实验结果表明，多次的超声清洗和水中浸泡对实施例1粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管涂层的粘附力和润滑性能没有影响，摩擦系数无明显变化，粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管的摩擦系数仅为普通导尿管的百分之一左右，这说明润滑涂层与管壁结合牢固，涂层稳定性强。经过多次超声清洗后，而普通底涂涂层的导管，因底涂涂层粘附力低，涂层不牢固导致润滑表涂涂层脱落，随着超声清洗次数的增多，润滑性能下降，摩擦系数逐渐增大。The experimental results show that multiple ultrasonic cleaning and immersion in water have no effect on the adhesion and lubricating properties of the lubricating coating with enhanced adhesion in Example 1 and its medical interventional catheter coating with lubricating and antibacterial functions, and the friction coefficient has no effect. Significant changes, the friction coefficient of the lubricating coating with enhanced adhesion and its lubricating and antibacterial medical interventional catheter is only about one percent of that of the ordinary urinary catheter, which shows that the lubricating coating is firmly combined with the tube wall, and the coating Layer stability. After repeated ultrasonic cleaning, the lubricating surface coating falls off due to the low adhesion of the primer coating and the weak coating of the ordinary primer coating. With the increase of ultrasonic cleaning times, the lubricating performance decreases. The coefficient of friction increases gradually.
3)涂层润滑性测试2：3) Coating Lubricity Test 2:
本发明采用MXD-02摩擦系数仪对实施例1中具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管(实施例组)、仅具有粘附力增强的底涂涂层的单层涂层医用介入类导管(对照组)以及未改性医用介入类导管(未改性组)进行摩擦系数的测试。首先分别将以上3组医用介入类导管用清水浸泡30s，然后固定在凹槽板上，向储水槽注入水直至试样完全浸泡其中。将200g的标准滑块轻放入于试样上方，由传感器连接杆拖动滑块以100mm/min的速度运动，测出动摩擦系数，结果如表3所示，表3为具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管与仅具有粘附力增强的底涂涂层的单层涂层医用介入类导管的摩擦系数。The present invention adopts MXD-02 friction coefficient meter to the medical interventional catheter (Example group) with double-layer coating structure with lubricating surface coating and primer coating with enhanced adhesion in Example 1, only with adhesive The adhesion-enhancing primer-coated single-coat medical interventional catheter (control group) and unmodified medical interventional catheter (unmodified group) were tested for coefficient of friction. First, the above three groups of medical interventional catheters were soaked in water for 30s, then fixed on the groove plate, and water was injected into the water storage tank until the samples were completely immersed in it. Put the 200g standard slider on top of the sample lightly, drag the slider by the sensor connecting rod to move at a speed of 100mm/min, and measure the coefficient of kinetic friction. The results are shown in Table 3. Coefficient of friction of a medical interventional catheter with a double-coated structure of layers and an adhesion-enhancing primer coating versus a single-coat medical interventional catheter with only the adhesion-enhancing primer coating.
表3具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管与仅具有粘附力增强的底涂涂层的单层涂层医用介入类导管的摩擦系数Table 3 Medical interventional catheters with a two-layer coating structure with a lubricating topcoat and an adhesion-enhancing primer coating versus a single-coat medical interventional catheter with only an adhesion-enhancing primer coating coefficient of friction
实验结果表明，具有粘附力增强的底涂涂层的单层涂层医用介入类导管不具备良好的润滑性能，摩擦系数与未改性样品相比无明显变化。具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管具有很好的润滑性能，润滑涂层通过底涂涂层作用与导管管壁结合牢固，二者在润滑性能方面有显著性差异。The experimental results show that the single-layer coated medical interventional catheter with the adhesion-enhancing primer coating does not have good lubricating properties, and the friction coefficient has no significant change compared with the unmodified sample. The medical interventional catheter with a double-layer coating structure with a lubricating surface coating and a primer coating with enhanced adhesion has good lubricating properties. The lubricating coating is firmly combined with the catheter wall through the primer coating. There is a significant difference between the two in terms of lubricating performance.
4)涂层安全性测试4) Coating safety test
将实施例1-4制得的负载润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管(实施例组)、负载相同润滑表涂涂层和普通底涂涂层的医用介入导管(对照组)以及未改性医用介入类导管(未改性组)进行引发剂析出检测试验。其中，负载相同润滑表涂涂层和普通底涂涂层的医用介入导管(对照组)是通过小分子光引发剂固定到导管表面。分别将以上3组样品在温度60℃，功率200w的超声条件下水溶液浸泡6h，取浸泡后的溶液通过红外分光光度计检测每组样品吸光度情况，根据峰值变化判断小分子光引发剂析出情况。表4为具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管的引发剂析出情况The medical interventional catheter (Example Group) with a double-layer coating structure of the loaded lubricating surface coating and the adhesion-enhancing primer coating prepared in Examples 1-4, loaded with the same lubricating surface coating and The general primer-coated medical interventional catheter (control group) and the unmodified medical interventional catheter (unmodified group) were tested for initiator precipitation. Among them, the medical interventional catheter (control group) loaded with the same lubricating surface coating and common primer coating was fixed to the surface of the catheter by a small molecule photoinitiator. The above three groups of samples were soaked in aqueous solution for 6 h under the ultrasonic conditions of temperature 60 °C and power 200 w respectively, and the soaked solution was taken to detect the absorbance of each group of samples by infrared spectrophotometer, and the precipitation of small molecule photoinitiators was judged according to the peak change. Table 4 shows the initiator precipitation of medical interventional catheters with a double-layer coating structure with a lubricating surface coating and an adhesion-enhancing primer coating
表4具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管的引发剂析出情况Table 4 Initiator precipitation of medical interventional catheters with double-layer coating structure with lubricating surface coating and adhesion-enhancing primer coating
实验结果表明，经过长时间的浸泡具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构的医用介入类导管无引发剂析出，表明光引发型阴阳离子复合物型底层在固化时会发生Norrish II反应和重组反应，实现底涂层在基体材料表面的化学键固定以及涂层内部的自身交联，在有效提高低涂层对基底材料粘附性的同时，还增加了提高涂层自身强度，提高涂层的安全性能。The experimental results show that after long-term immersion, the medical interventional catheter with a double-layer coating structure with a lubricating surface coating and an adhesion-enhancing primer coating has no initiator precipitation, indicating that the photo-initiated anion-cation complex type When the bottom layer is cured, Norrish II reaction and recombination reaction will occur to realize the chemical bond fixation of the primer layer on the surface of the base material and the self-crosslinking inside the coating layer. While effectively improving the adhesion of the low layer coating to the base material, it also increases In order to improve the strength of the coating itself and improve the safety performance of the coating.
5)抗凝血性测试：5) Anticoagulant test:
将实施例1～4制得的双层涂层结构的医用介入类导管在新鲜制得的富含血小板血浆中37℃孵化60min后，采用扫描电子显微镜拍摄置针套管表面的血小板形貌。为确保实验真实性和可信性，进行3次重复实验的平均值来得出数据，其中，未进行处理的留置针套管作为阴性对照组(厂家：山东威高集团医用高分子制品股份有限公司)。结果如图3～4所示，图3为未处理套管表面的血小板形貌照片，图4为本发明实施例2得到的具有双层涂层结构的留置针套管表面的血小板形貌照片。The double-coated medical interventional catheters prepared in Examples 1 to 4 were incubated in freshly prepared platelet-rich plasma at 37° C. for 60 min, and then the morphology of platelets on the surface of the needle-inserting cannula was photographed with a scanning electron microscope. In order to ensure the authenticity and reliability of the experiment, the average value of 3 repeated experiments was carried out to obtain the data, among which, the untreated indwelling needle cannula was used as the negative control group (manufacturer: Shandong Weigao Group Medical Polymer Products Co., Ltd. ). The results are shown in Figures 3 to 4. Figure 3 is a photo of the platelet morphology on the surface of the untreated cannula, and Figure 4 is a photo of the platelet morphology on the surface of the indwelling needle cannula with a double-layer coating structure obtained in Example 2 of the present invention. .
由图3～4可以看出，未处理留置针套管表面粘附有大量血小板，且血小板呈现铺展、完全铺展的激活状态。本发明实施例2得到的具有双层涂层结构留置针套管表面的粘附有少数的血小板，且血小板呈现圆形、梭形的未激活状态。考虑血小板粘附和激活在凝血过程中发挥着重要作用，说明本发明提供的具有润滑表涂涂层和粘附力增强的底涂涂层的双层涂层结构留置针套管可以减少凝血现象的发生概率。It can be seen from Figures 3 to 4 that a large number of platelets adhere to the surface of the untreated indwelling needle cannula, and the platelets are in an activated state of spreading and completely spreading. A few platelets adhered to the surface of the indwelling needle cannula with a double-layer coating structure obtained in Example 2 of the present invention, and the platelets were in a round, fusiform inactivated state. Considering that platelet adhesion and activation play an important role in the coagulation process, it shows that the double-coated structure indwelling needle cannula provided by the present invention with a lubricating surface coating and an adhesion-enhancing primer coating can reduce the coagulation phenomenon probability of occurrence.
6)抗菌性测试1：6) Antibacterial test 1:
将实施例1～4制得的具有双层涂层结构的医用介入导管和未涂层处理的医用介入导管灭菌，无菌实验条件下，在浓度为1X106cfu/mL的金黄色葡萄球菌的LB营养液中培养24h，随后取出导管，进行低功率超声处理、稀释，取稀释后的菌液在固体LB平板培养中37℃培养12h，对平板培养基上的菌落进行计数，测定医用导管表面的细菌数量，图5为未涂层处理医用导管培养后的菌落情况，图6为具有双层涂层结构的医用介入导管培养后的菌落情况。进行3次重复实验取平均值，结果如表4所示。Sterilize the medical interventional catheters with a double-layer coating structure and the uncoated medical interventional catheters prepared in Examples 1-4, under aseptic experimental conditions, at a concentration of 1× 10 6 cfu/mL Staphylococcus aureus Incubate in solid LB nutrient solution for 24h, then take out the catheter, carry out low-power ultrasonic treatment and dilution, take the diluted bacterial liquid and cultivate it in solid LB plate culture at 37 °C for 12h, count the colonies on the plate medium, and determine the medical catheter. The number of bacteria on the surface, Figure 5 shows the colony situation after the uncoated medical catheter is cultured, and Figure 6 shows the colony situation after the medical interventional catheter with a double-layer coating structure is cultured. Three repeated experiments were performed to obtain the average value, and the results are shown in Table 4.
表5医用导管表面的活细菌数量Table 5 Number of live bacteria on the surface of medical catheters
由表5可以看出，即便不加润滑油，粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管就可以有效降低导管表面的活细菌数量。往粘附力增强的润滑涂层及其具有润滑抗菌功能的医用介入类导管中注入润滑油后，医用导管的表面的活细菌数量进一步降低，维持在很低的水平。It can be seen from Table 5 that even without lubricating oil, the lubricating coating with enhanced adhesion and the medical interventional catheter with lubricating and antibacterial function can effectively reduce the number of live bacteria on the surface of the catheter. After injecting lubricating oil into the lubricating coating with enhanced adhesion and the medical interventional catheter with lubricating and antibacterial function, the number of viable bacteria on the surface of the medical catheter is further reduced and maintained at a very low level.
7)抗菌性测试2：7) Antibacterial test 2:
在无菌试验操作环境中，37℃培养金黄色葡萄球菌，将实施例1所述的具有润滑表涂涂层和粘附力增强的底层涂层的双层涂层结构的医用介入类导管(实施例组)、具有润滑表涂涂层和普通底层涂层的双层涂层结构的医用介入类导管(对照组)和未涂层处理的医用介入导管(未改性组)浸泡在金黄色葡萄球菌浓度为1X 106cfu/mL的LB溶液中，37℃培养6h后取出，用4％多聚甲醛固定4h，乙醇梯度脱水后，采用扫描电子显微镜观察实施例组和对照组医用介入类导管表面细菌粘附和死亡情况，如图7、图8和图9。In a sterile test operating environment, Staphylococcus aureus was cultured at 37°C, and the medical interventional catheter ( Example group), the medical interventional catheter (control group) and the uncoated medical interventional catheter (unmodified group) with a double-layer coating structure of lubricating surface coating and common bottom coating were soaked in golden yellow Staphylococcus in LB solution with a concentration of 1X 10 6 cfu/mL, cultured at 37°C for 6 hours, taken out, fixed with 4% paraformaldehyde for 4 hours, dehydrated with ethanol gradient, and observed by scanning electron microscope for medical interventional drugs in the example group and the control group. Bacterial adhesion and death on the catheter surface are shown in Figure 7, Figure 8 and Figure 9.
实验结果表明，图7为未改性组医用导管表面细菌粘附和死亡情况，结果表明未涂层处理的医用导管表面粘附了大量的细菌，形态为活细菌；图8为对照组具有润滑表涂涂层和普通底层涂层的双层涂层结构的医用介入类导管表面细菌情况，结果表明润滑表涂涂层有效抑制细菌粘附，只有少量细菌粘附在导管表面，因底层涂层不具有杀菌功能，所以粘附的细菌形态完整都是活细菌，表面对照组导管表面涂层只具有抗粘附功能；图9为实施例组具有润滑表涂涂层和粘附力增强的底层涂层的双层涂层结构的医用介入类导管表面细菌情况，结果表明润滑表涂涂层有效抑制细菌粘附，只有少量细菌粘附在导管表面，且底层涂层具有杀菌功能，所以粘附的细菌形态破裂为死细菌，表明实施例组导管表面涂层为抗杀结合表面。The experimental results show that Figure 7 shows the adhesion and death of bacteria on the surface of the medical catheter in the unmodified group. The results show that a large number of bacteria adhere to the surface of the uncoated medical catheter, and the morphology is live bacteria; Figure 8 shows the control group with lubrication. The bacteria on the surface of the medical interventional catheter with the double-layer coating structure of the surface coating and the ordinary bottom coating. The results show that the lubricating surface coating can effectively inhibit the adhesion of bacteria, and only a small amount of bacteria adhere to the surface of the catheter. It does not have bactericidal function, so the adhered bacteria are all live bacteria, and the surface coating of the catheter in the control group only has anti-adhesion function; Figure 9 shows the example group with a lubricating surface coating and a bottom layer with enhanced adhesion The bacteria on the surface of the medical interventional catheter with the double-layer coating structure of the coating. The results show that the lubricating surface coating can effectively inhibit the adhesion of bacteria, only a small amount of bacteria adhere to the surface of the catheter, and the bottom coating has a bactericidal function, so the adhesion The bacterial morphology was broken into dead bacteria, indicating that the catheter surface coating of the example group was an anti-kill binding surface.
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。The above are only the preferred embodiments of the present invention. It should be pointed out that for those skilled in the art, without departing from the principles of the present invention, several improvements and modifications can be made. It should be regarded as the protection scope of the present invention.
Claims (11)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210415649.4A CN114699564B (en) | 2022-04-20 | 2022-04-20 | Adhesion-enhanced lubricating coating, application thereof and medical intervention catheter |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210415649.4A CN114699564B (en) | 2022-04-20 | 2022-04-20 | Adhesion-enhanced lubricating coating, application thereof and medical intervention catheter |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114699564A true CN114699564A (en) | 2022-07-05 |
| CN114699564B CN114699564B (en) | 2023-05-23 |
Family
ID=82174069
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210415649.4A Active CN114699564B (en) | 2022-04-20 | 2022-04-20 | Adhesion-enhanced lubricating coating, application thereof and medical intervention catheter |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114699564B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114848923A (en) * | 2022-04-20 | 2022-08-05 | 威高集团有限公司 | A dual-modulus multifunctional self-adaptive coating, its application and a medical interventional catheter |
| CN115779159A (en) * | 2022-12-01 | 2023-03-14 | 中山大学 | High-strength-toughness wear-resistant hydrophilic lubricating coating grafted on surface of medical instrument and preparation method thereof |
| CN115814158A (en) * | 2022-12-01 | 2023-03-21 | 中山大学 | Articular cartilage-like wear-resistant lubricating coating and preparation method thereof |
| CN116350856A (en) * | 2023-02-17 | 2023-06-30 | 中国科学院长春应用化学研究所 | A kind of central venous catheter coating composition and central venous catheter |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998058990A1 (en) * | 1997-06-20 | 1998-12-30 | Coloplast A/S | A hydrophilic coating and a method for the preparation thereof |
| CN107405430A (en) * | 2015-06-08 | 2017-11-28 | 厦门杰美特涂层科技有限公司 | Include the coating composition of thickening bottom |
| CN107638612A (en) * | 2017-11-08 | 2018-01-30 | 中国科学院长春应用化学研究所 | A kind of anti-coagulation anti-bacterial type remaining needle sleeve pipe and preparation method thereof |
| CN109966560A (en) * | 2019-03-13 | 2019-07-05 | 业聚医疗器械(深圳)有限公司 | A kind of medical catheter hydrophilic lubrication coating of photocuring and preparation method thereof |
-
2022
- 2022-04-20 CN CN202210415649.4A patent/CN114699564B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998058990A1 (en) * | 1997-06-20 | 1998-12-30 | Coloplast A/S | A hydrophilic coating and a method for the preparation thereof |
| CN107405430A (en) * | 2015-06-08 | 2017-11-28 | 厦门杰美特涂层科技有限公司 | Include the coating composition of thickening bottom |
| US20180163152A1 (en) * | 2015-06-08 | 2018-06-14 | Jmedtech Coating Technologies Pte Ltd | Coating compositions comprising adhesion promoting base layer |
| CN107638612A (en) * | 2017-11-08 | 2018-01-30 | 中国科学院长春应用化学研究所 | A kind of anti-coagulation anti-bacterial type remaining needle sleeve pipe and preparation method thereof |
| CN109966560A (en) * | 2019-03-13 | 2019-07-05 | 业聚医疗器械(深圳)有限公司 | A kind of medical catheter hydrophilic lubrication coating of photocuring and preparation method thereof |
| US20200339906A1 (en) * | 2019-03-13 | 2020-10-29 | Orbusneich Medical Pte. Ltd. | Hydrophilic Lubricating Coating for Medical Catheters and Its Preparation Method |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114848923A (en) * | 2022-04-20 | 2022-08-05 | 威高集团有限公司 | A dual-modulus multifunctional self-adaptive coating, its application and a medical interventional catheter |
| CN115779159A (en) * | 2022-12-01 | 2023-03-14 | 中山大学 | High-strength-toughness wear-resistant hydrophilic lubricating coating grafted on surface of medical instrument and preparation method thereof |
| CN115814158A (en) * | 2022-12-01 | 2023-03-21 | 中山大学 | Articular cartilage-like wear-resistant lubricating coating and preparation method thereof |
| CN115779159B (en) * | 2022-12-01 | 2024-01-16 | 中山大学 | High-strength and high-toughness wear-resistant hydrophilic lubricating coating grafted on surface of medical instrument and preparation method thereof |
| CN115814158B (en) * | 2022-12-01 | 2024-02-23 | 中山大学 | Wear-resistant lubricating coating similar to articular cartilage and preparation method thereof |
| CN116350856A (en) * | 2023-02-17 | 2023-06-30 | 中国科学院长春应用化学研究所 | A kind of central venous catheter coating composition and central venous catheter |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114699564B (en) | 2023-05-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114699564A (en) | Adhesion-enhanced lubricating coating, application thereof and medical interventional catheter | |
| JP4948740B2 (en) | Method for surface modification of substrate and modified substrate obtained therefrom | |
| CN101429287B (en) | Highly blood coagulation resistant cellulose membrane material and preparation method thereof | |
| CN107638612B (en) | A kind of anticoagulant and antibacterial type indwelling needle cannula and preparation method thereof | |
| CN102357265A (en) | Surface modification polyurethane central venous catheter and preparation method thereof | |
| CN110665071A (en) | Antibacterial and anticoagulant type coating, functional material with antibacterial and anticoagulant type coating and preparation method thereof | |
| CN107759820A (en) | A kind of method and application process of silastic surface hydrophilic modifying | |
| Yu et al. | Regulable Polyelectrolyte‐Surfactant Complex for Antibacterial Biomedical Catheter Coating via a Readily Scalable Route | |
| Yu et al. | A tough, slippery, and anticoagulant double-network hydrogel coating | |
| CN114652900A (en) | A kind of hydrophilic antibacterial and anti-protein adhesion catheter, its preparation method and application | |
| Zhang et al. | Water‐Triggered Segment Orientation of Long‐Lasting Anti‐Biofouling Polyurethane Coatings on Biomedical Catheters via Solvent Exchange Strategy | |
| CN112048223A (en) | A kind of "anti-fouling-sterilization-release" multifunctional antibacterial surface and preparation method thereof | |
| Li et al. | Bio-inspired robust, superhydrophilic and superlubric artificial vascular endothelium coating for anti-thromboinflammation on blood-contacting devices | |
| CN115252901B (en) | Preparation method of modified biological valve material and modified biological valve material | |
| CN115814172B (en) | Anti-fouling wear-resistant hydrophilic lubricating coating grafted on surface of medical instrument and preparation method thereof | |
| Zhang et al. | Construction of the mussel-inspired PDAM/lysine/heparin composite coating combining multiple anticoagulant strategies | |
| Guo et al. | Tyramine-enhanced zwitterion hyaluronan hydrogel coating for anti-fouling and anti-thrombosis | |
| CN108129687B (en) | A kind of surface is the preparation method of the imitating cell outer-layer membrane structure coating of Phosphorylcholine | |
| CN115536919B (en) | A modified chitosan adhesive hydrogel and its preparation method and application | |
| CN103881026A (en) | Poly(N-vinylpyrrolidone) microgel as well as preparation method and application thereof | |
| Wen et al. | Recent advances in zwitterionic polymers-based non-fouling coating strategies for biomedical applications | |
| CN107828075A (en) | A kind of medical anticoagulant high polymer material and preparation method thereof | |
| CN105504328B (en) | A kind of room temperature coats the method for improving chitosan film blood compatibility in next step | |
| CN114848923B (en) | Dual-modulus multifunctional self-adaptive coating, application thereof and medical intervention catheter | |
| CN115322296B (en) | Heparin functionalized hydrogel and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |