CN115337472A - 一种涂层组合物、涂层及其制备方法、医疗器械 - Google Patents
一种涂层组合物、涂层及其制备方法、医疗器械 Download PDFInfo
- Publication number
- CN115337472A CN115337472A CN202211047723.8A CN202211047723A CN115337472A CN 115337472 A CN115337472 A CN 115337472A CN 202211047723 A CN202211047723 A CN 202211047723A CN 115337472 A CN115337472 A CN 115337472A
- Authority
- CN
- China
- Prior art keywords
- coating
- hyperbranched polyurethane
- polyurethane
- hyperbranched
- coating composition
- 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 63
- 239000011248 coating agent Substances 0.000 title claims abstract description 62
- 239000008199 coating composition Substances 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title abstract description 11
- 239000004814 polyurethane Substances 0.000 claims abstract description 107
- 229920002635 polyurethane Polymers 0.000 claims abstract description 107
- 239000000463 material Substances 0.000 claims abstract description 43
- 239000002318 adhesion promoter Substances 0.000 claims abstract description 23
- 229940124599 anti-inflammatory drug Drugs 0.000 claims abstract description 21
- 229920000249 biocompatible polymer Polymers 0.000 claims abstract description 17
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 claims description 43
- 239000000178 monomer Substances 0.000 claims description 29
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 21
- 230000008961 swelling Effects 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 239000011159 matrix material Substances 0.000 claims description 19
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 claims description 16
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 15
- 239000005058 Isophorone diisocyanate Substances 0.000 claims description 15
- NIMLQBUJDJZYEJ-UHFFFAOYSA-N isophorone diisocyanate Chemical compound CC1(C)CC(N=C=O)CC(C)(CN=C=O)C1 NIMLQBUJDJZYEJ-UHFFFAOYSA-N 0.000 claims description 15
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 14
- 229940043237 diethanolamine Drugs 0.000 claims description 14
- 229940074391 gallic acid Drugs 0.000 claims description 14
- 235000004515 gallic acid Nutrition 0.000 claims description 14
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 claims description 13
- BRRSNXCXLSVPFC-UHFFFAOYSA-N 2,3,4-Trihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(O)=C1O BRRSNXCXLSVPFC-UHFFFAOYSA-N 0.000 claims description 12
- MJORMRFQFZHIGF-UHFFFAOYSA-N 3,4-dihydroxy-1h-quinolin-2-one Chemical compound C1=CC=C2C(=O)C(O)=C(O)NC2=C1 MJORMRFQFZHIGF-UHFFFAOYSA-N 0.000 claims description 12
- 229920000642 polymer Polymers 0.000 claims description 9
- 229960000956 coumarin Drugs 0.000 claims description 8
- 235000001671 coumarin Nutrition 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 claims description 8
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 claims description 7
- -1 carboxyl bisphenol Chemical compound 0.000 claims description 7
- 229940016667 resveratrol Drugs 0.000 claims description 7
- 235000021283 resveratrol Nutrition 0.000 claims description 7
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 6
- 238000004132 cross linking Methods 0.000 claims description 6
- 229940068372 acetyl salicylate Drugs 0.000 claims description 5
- 239000011247 coating layer Substances 0.000 claims description 5
- PTBDIHRZYDMNKB-UHFFFAOYSA-N 2,2-Bis(hydroxymethyl)propionic acid Chemical compound OCC(C)(CO)C(O)=O PTBDIHRZYDMNKB-UHFFFAOYSA-N 0.000 claims description 4
- 229930185605 Bisphenol Natural products 0.000 claims description 4
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 3
- 229920000669 heparin Polymers 0.000 claims description 3
- 229960002897 heparin Drugs 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 229910000077 silane Inorganic materials 0.000 claims description 3
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 229910052804 chromium Inorganic materials 0.000 claims description 2
- 239000011651 chromium Substances 0.000 claims description 2
- 239000004632 polycaprolactone Substances 0.000 claims description 2
- 229920001610 polycaprolactone Polymers 0.000 claims description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 2
- 229960001860 salicylate Drugs 0.000 claims description 2
- 239000000758 substrate Substances 0.000 abstract description 20
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 7
- 230000010100 anticoagulation Effects 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 6
- 239000003146 anticoagulant agent Substances 0.000 abstract description 2
- 229940127219 anticoagulant drug Drugs 0.000 abstract description 2
- 238000002474 experimental method Methods 0.000 abstract description 2
- 206010061218 Inflammation Diseases 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- UKLDJPRMSDWDSL-UHFFFAOYSA-L [dibutyl(dodecanoyloxy)stannyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)O[Sn](CCCC)(CCCC)OC(=O)CCCCCCCCCCC UKLDJPRMSDWDSL-UHFFFAOYSA-L 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 7
- 239000012975 dibutyltin dilaurate Substances 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000002184 metal Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 125000005442 diisocyanate group Chemical group 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000007943 implant Substances 0.000 description 5
- 230000002572 peristaltic effect Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 4
- 229920000307 polymer substrate Polymers 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- CADZRPOVAQTAME-UHFFFAOYSA-L calcium;hydroxy phosphate Chemical compound [Ca+2].OOP([O-])([O-])=O CADZRPOVAQTAME-UHFFFAOYSA-L 0.000 description 3
- 229920000587 hyperbranched polymer Polymers 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- UPMLOUAZCHDJJD-UHFFFAOYSA-N 4,4'-Diphenylmethane Diisocyanate Chemical compound C1=CC(N=C=O)=CC=C1CC1=CC=C(N=C=O)C=C1 UPMLOUAZCHDJJD-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 239000005057 Hexamethylene diisocyanate Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000002429 anti-coagulating effect Effects 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000000919 ceramic Substances 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- RRAMGCGOFNQTLD-UHFFFAOYSA-N hexamethylene diisocyanate Chemical compound O=C=NCCCCCCN=C=O RRAMGCGOFNQTLD-UHFFFAOYSA-N 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 150000002527 isonitriles Chemical class 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 2
- 229910052721 tungsten Inorganic materials 0.000 description 2
- 239000010937 tungsten Substances 0.000 description 2
- BOZRCGLDOHDZBP-UHFFFAOYSA-N 2-ethylhexanoic acid;tin Chemical compound [Sn].CCCCC(CC)C(O)=O BOZRCGLDOHDZBP-UHFFFAOYSA-N 0.000 description 1
- KKJUPNGICOCCDW-UHFFFAOYSA-N 7-N,N-Dimethylamino-1,2,3,4,5-pentathiocyclooctane Chemical compound CN(C)C1CSSSSSC1 KKJUPNGICOCCDW-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 238000006691 Passerini condensation reaction Methods 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 229910001069 Ti alloy Inorganic materials 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
- MCMNRKCIXSYSNV-UHFFFAOYSA-N ZrO2 Inorganic materials O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 125000002462 isocyano group Chemical group *[N+]#[C-] 0.000 description 1
- 239000010985 leather Substances 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229960000965 nimesulide Drugs 0.000 description 1
- HYWYRSMBCFDLJT-UHFFFAOYSA-N nimesulide Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1=CC=CC=C1 HYWYRSMBCFDLJT-UHFFFAOYSA-N 0.000 description 1
- 229910052758 niobium Inorganic materials 0.000 description 1
- 239000010955 niobium Substances 0.000 description 1
- GUCVJGMIXFAOAE-UHFFFAOYSA-N niobium atom Chemical compound [Nb] GUCVJGMIXFAOAE-UHFFFAOYSA-N 0.000 description 1
- 229910052755 nonmetal Inorganic materials 0.000 description 1
- RVTZCBVAJQQJTK-UHFFFAOYSA-N oxygen(2-);zirconium(4+) Chemical compound [O-2].[O-2].[Zr+4] RVTZCBVAJQQJTK-UHFFFAOYSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229910052715 tantalum Inorganic materials 0.000 description 1
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical compound [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052726 zirconium Inorganic materials 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/0005—Use of materials characterised by their function or physical properties
- A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/30—Low-molecular-weight compounds
- C08G18/32—Polyhydroxy compounds; Polyamines; Hydroxyamines
- C08G18/3203—Polyhydroxy compounds
- C08G18/3206—Polyhydroxy compounds aliphatic
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/30—Low-molecular-weight compounds
- C08G18/32—Polyhydroxy compounds; Polyamines; Hydroxyamines
- C08G18/3203—Polyhydroxy compounds
- C08G18/3218—Polyhydroxy compounds containing cyclic groups having at least one oxygen atom in the ring
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/30—Low-molecular-weight compounds
- C08G18/32—Polyhydroxy compounds; Polyamines; Hydroxyamines
- C08G18/3271—Hydroxyamines
- C08G18/3275—Hydroxyamines containing two hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/30—Low-molecular-weight compounds
- C08G18/34—Carboxylic acids; Esters thereof with monohydroxyl compounds
- C08G18/348—Hydroxycarboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/30—Low-molecular-weight compounds
- C08G18/38—Low-molecular-weight compounds having heteroatoms other than oxygen
- C08G18/3819—Low-molecular-weight compounds having heteroatoms other than oxygen having nitrogen
- C08G18/3842—Low-molecular-weight compounds having heteroatoms other than oxygen having nitrogen containing heterocyclic rings having at least one nitrogen atom in the ring
- C08G18/3844—Low-molecular-weight compounds having heteroatoms other than oxygen having nitrogen containing heterocyclic rings having at least one nitrogen atom in the ring containing one nitrogen atom in the ring
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/67—Unsaturated compounds having active hydrogen
- C08G18/675—Low-molecular-weight compounds
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/74—Polyisocyanates or polyisothiocyanates cyclic
- C08G18/75—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic
- C08G18/751—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring
- C08G18/752—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring containing at least one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group
- C08G18/753—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring containing at least one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group containing one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group having a primary carbon atom next to the isocyanate or isothiocyanate group
- C08G18/755—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring containing at least one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group containing one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group having a primary carbon atom next to the isocyanate or isothiocyanate group and at least one isocyanate or isothiocyanate group linked to a secondary carbon atom of the cycloaliphatic ring, e.g. isophorone diisocyanate
-
- 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
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
-
- 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
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet 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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2150/00—Compositions for coatings
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明涉及医疗领域，具体是一种涂层组合物、涂层及其制备方法、医疗器械。本发明提供了一种涂层组合物，包括以下质量百分含量的组分：5wt％～30wt％超支化聚氨酯；5wt％～30wt％生物相容性聚合物；0.5wt％～30wt％抗炎药物；0.01wt％～2wt％粘附性促进剂。本发明提供的涂层组合物能够形成生物相容性和抗炎抗凝效果好的涂层，所述涂层能够与不同的基体材料牢固结合，适合应用于医疗器械中。实验表明，本发明所述涂层成功涂覆于不同的基底材料中；以聚氨酯基底为例，涂覆有所述涂层的聚氨酯基底的BCI值约为未涂覆的6倍，表明本发明所述涂层具有显著的抗炎抗凝能力且结合稳定。
Description
技术领域
本发明涉及医疗领域，具体是一种涂层组合物、涂层及其制备方法、医疗器械。
背景技术
植介入器械是植入治疗的必要工具，如中心静脉导管、PTCA导管、金属支架等，这类医疗器械与血液接触容易在医疗器械表面形成血栓，造成医疗器械失效。随着医学的发展与药物的研究，很多“绝症”得以治疗，但是植介入材料的血栓一直是世界难题。以中心静脉导管为例，材料的血液相容性对患者具有显著的影响，目前导管表面涂敷药物是一种便捷方法，但是这些药物对人体有副作用。为了提高材料的抗凝血性，材料表面改性可抑制血液与医疗器械起始接触引发的血栓，但由于植介入器械长期在血液环境中，血液微环境的变化会引起表面结构不稳定，改性大分子经常被氧化，而且缺乏响应性和自适应性，从而会引发后期和晚期血栓，同样威胁病人健康。
超支化聚合物是一种具有三维结构的高度支化大分子,由于其制备简单，成本较低，性能优越等特点，在纳米封装、药物控制释放及生物材料等领域受到广泛关注。具有智能响应和自适应性的超支化聚合物涂层容易制备、结构稳定，是医用涂层的发展方向。
发明内容
有鉴于此，本发明所要解决的技术问题在于提供一种涂层组合物、涂层及其制备方法、医疗器械，本发明提供的涂层组合物能够形成生物相容性和抗炎抗凝血效果好的涂层，所述涂层能够与不同的基体材料牢固结合，适合应用于医疗器械尤其是医用植入物中。
本发明提供了一种涂层组合物，包括以下质量百分含量的组分：
5wt％～30wt％超支化聚氨酯；
5wt％～30wt％生物相容性聚合物；
0.5wt％～30wt％抗炎药物；
0.01wt％～2wt％粘附性促进剂。
本发明所述超支化聚氨酯的分子链中含有大量的异氰基(-NCO)和氨基甲酸酯基(-NH-COO-),表现出高度的活性与极性，良好的流动性、溶解性，黏度低以及多功能性等特点，可与含有活泼氢的基材,如塑料、泡沫、织物、皮革、陶瓷等多孔材料,同时与玻璃、橡胶、金属等表面光洁的材料也有优良的化学粘接力，因此本发明所述超支化聚氨酯可用于不同材料的表面涂层的制备，通过增加功能基团，使涂层具有自适应性和智能响应性，可显著提升抗凝能力，适应血液微环境的变化，降低了植介入器械引发的病理反应，延长了器械使用寿命。
在本发明的某些实施例中，所述超支化聚氨酯选自没食子酸结构超支化聚氨酯、三羟基苯甲酸酯香豆素结构超支化聚氨酯、白藜芦醇结构超支化聚氨酯、三羟基喹啉结构超支化聚氨酯中的至少一种。在本发明的某些实施例中，所述超支化聚氨酯的结构如式1所示：
所述L选自
所述R为
其中，x+q+r+t≤12。在一个实施例中，所述超支化聚氨酯的结构如式2所示：
所述R、x、q、r、t和上述一样，不再赘述。
在本发明的某些实施例中，所述超支化聚氨酯选自没食子酸结构超支化聚氨酯，所述超支化聚氨酯由没食子酸、异佛尔酮二异氰酸酯和二羟基单体制备得到；或者，所述超支化聚氨酯选自三羟基苯甲酸酯香豆素结构超支化聚氨酯，所述超支化聚氨酯由三羟基苯甲酸酯香豆素、异佛尔酮二异氰酸酯和二羟基单体制备得到；或者，所述超支化聚氨酯选自白藜芦醇结构超支化聚氨酯，所述超支化聚氨酯由白藜芦醇、异佛尔酮二异氰酸酯和二羟基单体制备得到；或者，所述超支化聚氨酯选自三羟基喹啉单体结构超支化聚氨酯，所述超支化聚氨酯由三羟基喹啉、异佛尔酮二异氰酸酯和二羟基单体制备得到；所述二羟基单体选自羧基双酚、酚酞啉、二羟甲基丙酸、乙二醇或二乙醇胺中的至少一种。
在一个实施例中，所述超支化聚氨酯的支化度为0.3～0.7，优选为0.4～0.6。在一个实施例中，所述超支化聚氨酯在所述涂层组合物中的质量百分含量为5wt％～30wt％，优选为5wt％～20wt％，最优选为5wt％～15wt％。
本发明所述生物相容性聚合物为粘性和温敏性的生物相容性聚合物，能够提高涂层的润滑性能，同时具有较好的生物相容性。在本发明的某些实施例中，所述生物相容性聚合物选自聚乙烯吡咯烷酮、聚乙烯己内酰胺、聚乙二醇、聚己内酯，聚氨酯、肝素类聚合物及其共混物中的至少一种，优选选自聚乙烯吡咯烷酮、聚乙烯己内酰胺、聚N-异丙基丙烯酰胺、聚乙二醇、肝素类及其共混物中的至少一种。在一个实施例中，所述生物相容性聚合物在所述涂层组合物中的质量百分含量为5wt％～30wt％，优选为5wt％～20wt％，最优选为5wt％～15wt％。
本发明所述抗炎药物被包覆在所述涂层中，在血液环境中能够缓慢释放，达到抗慢性炎症的作用，当血液环境温度发生微小变化时，药物的释放速率也随即发生变化。在本发明的某些实施例中，所述抗炎药物选自乙酰水杨酸盐类、非乙酰基水杨酸盐类或非水杨酸类抗炎药中的至少一种，优选选自乙酰水杨酸盐类。在一个实施例中，所述抗炎药物优选为阿司匹林、对乙酰氨基酚、吲哚美辛、萘普生、萘普酮、双氯芬酸、布洛芬、尼美舒利、罗非昔布、塞来昔布中的至少一种。在一个实施例中，所述抗炎药物在所述涂层组合物中的质量百分含量为0.5wt％～30wt％，优选为0.5wt％～20wt％，更优选为0.5wt％～10wt％。
本发明所述粘附性促进剂能够促进所述超支化聚氨酯和所述生物相容性聚合物之间进行交联反应并包覆所述抗炎药物。在本发明的某些实施例中，所述粘附性促进剂选自钛酸酯类粘附性促进剂、硅烷类粘附性促进剂、铬络合物类粘附性促进剂中的至少一种，优选选自钛酸酯类粘附性促进剂、硅烷类粘附性促进剂中的至少一种。在一个实施例中，所述粘附性促进剂在所述涂层组合物中的质量百分含量为0.01wt％～2wt％，优选为0.01wt％～0.06wt％。
本发明提供了一种上述超支化聚氨酯的制备方法，包括：将三羟基单体、二羟基单体、二异氰酸酯和催化剂进行反应，得到上述超支化聚氨酯。
具体而言，本发明将三羟基单体、二羟基单体、二异氰酸酯和催化剂溶于溶剂中，在氮气环境下进行反应，反应后除去溶剂，得到上述超支化聚氨酯。
在本发明的某些实施例中，所述三羟基单体选自没食子酸、白藜芦醇、三羟基喹啉、三羟基苯甲酸酯香豆素中的至少一种，优选选自没食子酸，白藜芦醇或三羟基苯甲酸酯香豆素中的至少一种。其中，所述没食子酸的结构如式I1所示；所述白藜芦醇的结构如式I2所示；所述三羟基喹啉的结构如式I3所示；所述三羟基苯甲酸酯香豆素的结构如式I4所示。
在本发明的某些实施例中，所述二羟基单体选自羧基双酚、酚酞啉、二羟甲基丙酸、乙二醇或二乙醇胺中的至少一种；其中，所述羧基双酚的结构如式II1所示；所述酚酞啉的结构如式II2所示；所述二羟甲基丙酸的结构如式II3所示；所述乙二醇的结构如式II4所示；所述二乙醇胺的结构如式II5所示。
在本发明的某些实施例中，所述二异氰酸酯选自六亚甲基二异氰酸酯、异佛尔酮二异氰酸酯、二苯基甲烷二异氰酸酯中的至少一种；其中，所述六亚甲基二异氰酸酯的结构式如式III1所示；所述异佛尔酮二异氰酸酯的结构式如式III2所示；所述二苯基甲烷二异氰酸酯的结构式如式III3所示。在本发明的某些实施例中，所述催化剂选自二月桂酸二丁基锡、辛酸亚锡或辛酸锡中的至少一种。
本发明所述二羟基单体中，所述二乙醇胺具有特殊结构，可作为新支化点。当所述二羟基单体不包括二乙醇胺时，以质量份计，所述二羟基单体的用量为5份～10份，优选为5份～7份；当所述二羟基单体包括二乙醇胺时，以质量份计，所述二乙醇胺的用量为10份以内，优选为5份以内；其它所选的二羟基单体的用量为0份～10份，优选为0份～5份。
在本发明的某些实施例中，以质量份计，所述三羟基单体的用量为10份～30份，优选为10份～20份。所述二异氰酸酯的用量为30份～60份，优选为40份～60份；所述催化剂的用量为0.002份～0.1份，优选为0.005份～0.1份。在一个实施例中，所述反应的温度为80℃～100℃，优选为80℃～90℃；所述反应的时间为2.5h～5h，优选为3h～5h。
上述三羟基苯甲酸酯香豆素为具有抗炎药理活性结构三羟基单体，采用Passerini反应得到，其制备方法包括以下步骤：将没食子酸、苯甲醛和7-异腈-4-甲基香豆素在溶剂中反应，得到上述具有抗炎药理活性结构三羟基单体。
具体而言，本发明将没食子酸、苯甲醛和7-异腈-4-甲基香豆素加入到3mL～7mL干燥的二氯甲烷中，优选加入到4mL～6mL干燥的二氯甲烷中，搅拌并在氮气保护下进行回流反应，得到反应液；将所述反应液用10mL～30mL的二氯甲烷稀释，优选用10mL～20mL的二氯甲烷稀释，稀释后依次以稀盐酸和稀碳酸钠水溶液洗涤，分别除去残余的异腈和羧酸反应物，水洗，干燥，减压蒸除溶剂，柱层析得到上述具有抗炎药理活性结构三羟基单体。
在本发明的某些实施例中，所述没食子酸的用量为1mmol～3mmol，优选为1mmol～2mmol；所述苯甲醛的用量为1mmol～3mmol，优选为1mmol～2mmol；所述7-异腈-4-甲基香豆素的用量为1mmol～3mmol，优选为1mmol～2mmol。在一个实施例中，所述回流反应的时间为24h～72h，优选为24h～48h。
本发明提供了一种涂层，由上述涂层组合物形成。本发明所述涂层为一种集成性涂层，针对植介入器械从植入到服役全过程引起的病理环境进行设计。涂层中的超支化聚氨酯可与基底具有牢固的化学粘结力，提高涂层稳定性，同时与具有温敏性和生物相容性聚合物连接、交联，并负载抗炎症药物。涂层中药物在血液环境中缓慢释放，达到抗慢性炎症的作用，当血液环境温度发生微小变化时，药物的释放速率也随即发生变化。在本发明的某些实施例中，所述涂层中的抗炎药物占所述涂层总质量的分数为0.1％～30％，优选为0.1％～20％，更优选为1％～20％，最优选为5％～15％。在一个实施例中，所述涂层中的抗炎药物占所述涂层总质量的分数为1％、3％、5％、10％或15％。
本发明还提供了一种上述涂层的制备方法，包括将基体材料置于所述超支化聚氨酯的溶液中溶胀，溶胀后置于所述生物相容性聚合物、抗炎药物和粘附性促进剂的溶液中继续溶胀，溶胀后进行交联反应，在所述基体材料表面形成上述涂层。
本发明首先将基体材料置于所述超支化聚氨酯的溶液中溶胀。具体而言，本发明首先将所述超支化聚氨酯溶于溶剂中，然后将所述基体材料置于所述超支化聚氨酯的溶液中溶胀。本发明所述超支化聚氨酯和上述一样，不再赘述。在一个实施例中，所述溶剂选自N,N二甲基甲酰胺或四氢呋喃中的至少一种。在一个实施例中，所述溶胀的时间为10min～60min，优选为20min～60min，更优选为20min～40min，最优选为20min～30min。
本发明将基体材料置于所述超支化聚氨酯的溶液中溶胀后，将所述基体材料置于所述生物相容性聚合物、抗炎药物和粘附性促进剂的溶液中继续溶胀。具体而言，本发明将所述生物相容性聚合物、抗炎药物和粘附性促进剂溶于溶剂中，将所述基体材料置于所述生物相容性聚合物、抗炎药物和粘附性促进剂的溶液中继续溶胀。本发明所述生物相容性聚合物、抗炎药物和粘附性促进剂和上述一样，不再赘述。在一个实施例中，所述溶剂为乙醇的水溶液；所述乙醇和水的体积比为6～9:1～4，优选为7:3。在一个实施例中，所述溶胀的时间为10min～60min，优选为20min～60min，更优选为20min～40min，最优选为20min～30min。
本发明将基体材料置于所述超支化聚氨酯的溶液中溶胀，并置于所述生物相容性聚合物、抗炎药物和粘附性促进剂的溶液中继续溶胀后，进行交联反应，在所述基体材料表面形成上述涂层。本发明所述交联反应为加热交联反应。在一个实施例中，所述反应的温度为60℃～150℃，优选为80℃～110℃。在一个实施例中，所述反应的时间为10h～40h，优选为24h。
本发明提供了一种医疗器械，包括基体材料和设置在所述基体材料表面上的涂层；所述涂层由上述的涂层组合物形成或者所述涂层为上述的涂层或者所述涂层为上述的制备方法得到的涂层。在本发明的某些实施例中，所述基体材料表面上的涂层的厚度为1μm～30μm，优选为1μm～25μm，更优选为2μm～20μm。
本发明所述医疗器械包括但不限于植介入医疗器械和医疗植入物，术语“植介入医疗器械”和“植入物”在此处同义使用并且理解为包括医疗或治疗性植入物。在本发明的某些实施例中，所述医疗器械为医用内置假体、医用导管、医用支架或医用缝合线。在一个实施例中，所述医疗器械为血管内置假体或管腔内置假体。
本发明所述基体材料选自金属基体材料、无机非金属基体材料或聚合物基体材料，优选为金属基体材料。在本发明的某些实施例中，所述基体材料选自金属基体材料，所述金属基体材料由铁、镁、镍、钨、钛、锆、铌、钽、锌或硅中的至少一种组成。在本发明的某些实施例中，所述基体材料选自金属基体材料，所述金属基体材料由锂、钠、钾、钙、锰、铁或钨中的至少一种组成。在本发明的某些实施例中，所述基体材料选自无机非金属基体材料，所述无机非金属基体材料由二氧化锆、羟基磷酸钙中的至少一种组成。在本发明的某些实施例中，所述基体材料选自聚合物基体材料，所述聚合物基体材料由聚氨酯类聚合物、聚砜类聚合物、聚酯类聚合物、聚醚类聚合物中的至少一种组成。
本发明提供了一种涂层组合物，包括以下质量百分含量的组分：5wt％～30wt％超支化聚氨酯；5wt％～30wt％生物相容性聚合物；0.5wt％～30wt％抗炎药物；0.01wt％～2wt％粘附性促进剂。本发明提供的涂层组合物能够形成生物相容性和抗炎抗凝血效果好的涂层，所述涂层能够与不同的基体材料牢固结合，适合应用于医疗器械尤其是医用植入物中。实验表明，本发明所述涂层成功涂覆于不同的基底材料中；以聚氨酯基底为例，涂覆有本发明所述涂层的聚氨酯基底的BCI值约为未加涂层的聚氨酯基底的6倍，表明本发明所述涂层具有显著的抗凝血能力且结合稳定。
附图说明
图1为聚氨酯裸导管形成涂层前后的红外光谱图；
图2为对形成涂层前后的聚氨酯基底材料的酶标仪测试吸光值图。
具体实施方式
本发明公开了一种涂层组合物、涂层及其制备方法、医疗器械。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，它们都被视为包括在本发明。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。
以下结合实施例对本发明进行进一步阐述：
实施例1含没食子酸结构超支化聚氨酯结构集成型涂层应用聚合物基底
在85℃下，将2.3g没食子酸、12.4g异佛尔酮二异氰酸酯和0.05g二月桂酸二丁基锡置于三口瓶中，机械搅拌，通氮气及冷凝回流，反应2h，温度设置为5℃，将含有二乙醇胺0.001g的N,N二甲基甲酰胺溶液通过蠕动泵滴加到上述溶液中，反应1h，得到没食子酸结构超支化聚氨酯，其支化度为0.52。
将得到的没食子酸结构超支化聚氨酯溶解于质量分数为10％的N,N二甲基甲酰胺，将聚氨酯基底材料置于没食子酸结构超支化聚氨酯溶液中溶胀10min，取出置于溶有2g分子量为40000Da的聚乙烯吡咯烷酮、0.7g分子量为200Da的聚乙二醇和0.2g钛酸四丁酯的水-乙醇(7:3)溶液中10min，取出置于10mL含有分子量为100000Da的肝素钠0.1g的水溶液中10min，在聚氨酯基底材料表面形成本发明所述涂层，在真空烘箱100℃干燥1天。
对形成涂层前后的聚氨酯基底材料进行红外光谱测试，结果如图1所示。图1为聚氨酯裸导管形成涂层前后的红外光谱图。对比两样品表面红外光谱曲线，聚氨酯裸导管表面在形成涂层前后有明显区别，形成涂层后，聚氨酯原有吸收峰强度被削弱，取而代之的是涂层成分中基团的特征吸收峰，1707cm-1处为聚乙烯吡咯烷酮酰胺羰基峰，1530cm-1为苯环吸收峰，1241cm-1为醚键吸收峰，718cm-1为醇羟基吸收峰。
对形成涂层前后的聚氨酯基底材料通过酶标仪测试吸光值，将血液收集于有3.6mL的3.5％柠檬酸钠的小瓶中以防凝固，将200μL所述血液分别滴加在涂层和聚氨酯基底材料表面，然后分别滴加20μL的浓度为0.2mol/L的氯化钙溶液，37℃下孵育5min。完成后，将25mL的去离子水加入以破坏未凝的红细胞，运用酶标仪检测涂层抗凝血能力。以BCI代表抗凝能力大小，BCI数值越大，抗凝效果越好。所述BCI的计算公式为：
在公式(1)中，ODsample为酶标仪所测样品在541nm处吸光度。ODblank为将新鲜的200μL血液用25mL去离子水溶血后样品在541nm处的吸光度。
通过计算得到形成涂层前后的聚氨酯基底材料的抗凝能力BCI值，结果如图2所示，图2为对形成涂层前后的聚氨酯基底材料的酶标仪测试吸光值图。图2显示了涂层与聚氨酯基底的BCI大小，两个数值之间的差异显示本发明中所述涂层有显著的抗凝血能力。
实施例2含三羟基苯甲酸酯香豆素结构超支化聚氨酯结构集成型涂层应用聚合物基底
将0.3g的没食子酸、0.1g的苯甲醛和1g的7-异腈-4-甲基香豆素加入到4mL干燥的二氯甲烷中，搅拌反应，在氮气保护下回流反应48h，停止反应。反应液以10mL的二氯甲烷稀释后，依次以稀盐酸、稀碳酸钠水溶液洗涤，分别除去残余的异腈和羧酸反应物，水洗，干燥，减压蒸除溶剂，柱层析得纯品三羟基苯甲酸酯香豆素结构单体。
取0.8g上述制备的三羟基苯甲酸酯香豆素结构单体，0.46g二异氰酸酯，0.002g乙二醇，0.001g二乙醇胺和约0.002g二月桂酸二丁基锡溶于N,N二甲基甲酰胺，通氮气，在80℃下反应3h，旋转蒸发除去溶剂，得到三羟基苯甲酸酯香豆素结构超支化聚氨酯，其支化度为0.57。
将得到的三羟基苯甲酸酯香豆素结构超支化聚氨酯溶解于质量分数为10％的N,N二甲基甲酰胺，将聚氨酯基底材料置于三羟基苯甲酸酯香豆素结构超支化聚氨酯溶液中溶胀10min，取出置于溶有2g分子量为40000Da的聚乙烯吡咯烷酮、0.7g分子量为200Da的聚乙二醇和0.2g钛酸四丁酯的水-乙醇(7:3)溶液中10min，取出置于10mL含有分子量为100000Da的肝素钠0.1g的水溶液中10min，在聚氨酯基底材料表面形成本发明所述涂层，在真空烘箱100℃干燥1天。
实施例3含白藜芦醇结构超支化聚氨酯结构集成型涂层应用聚合物基底
在85℃下，将4g白藜芦醇、12.4g异佛尔酮二异氰酸酯和0.05g二月桂酸二丁基锡置于三口瓶中，机械搅拌，通氮气及冷凝回流，反应2h，温度设置为5℃，将含有二乙醇胺0.01g的N,N二甲基甲酰胺溶液通过蠕动泵滴加到上述溶液中，反应1h，得到白藜芦醇结构超支化聚氨酯，其支化度为0.62。
将得到的白藜芦醇结构超支化聚氨酯溶解于N,N二甲基甲酰胺质量分数10％，将聚氨酯基底材料置于白藜芦醇结构超支化聚氨酯溶液中溶胀10min，取出置于溶有2g分子量为40000Da的聚乙烯吡咯烷酮、0.7g分子量为200Da的聚乙二醇和0.2g钛酸四丁酯的水-乙醇(7:3)溶液中10min，取出置于10mL含有分子量为100000Da的肝素钠0.1g的水溶液中10min，在聚氨酯基底材料表面形成本发明所述涂层，在真空烘箱100℃干燥1天。
实施例4含三羟基喹啉结构超支化聚氨酯结构集成型涂层应用聚合物基底
在85℃下，将4.6g三羟基喹啉、12.4g异佛尔酮二异氰酸酯，0.05g二月桂酸二丁基锡置于三口瓶中，机械搅拌，通氮气及冷凝回流，反应2h，温度设置为5℃，将含有二乙醇胺0.02g的N,N二甲基甲酰胺溶液通过蠕动泵滴加到上述溶液中，反应1h，得到三羟基喹啉结构超支化聚氨酯，其支化度为0.49。
将得到的三羟基喹啉结构超支化聚氨酯溶解于质量分数为10％的N,N二甲基甲酰胺，将聚氨酯基底材料置于三羟基喹啉结构超支化聚氨酯溶液中溶胀10min，取出置于溶有2g分子量为40000Da的聚乙烯吡咯烷酮、0.7g分子量为200Da的聚乙二醇和0.2g钛酸四丁酯的水-乙醇(7:3)溶液中10min，取出置于10mL含有分子量为100000Da的肝素钠0.1g的水溶液中10min，在聚氨酯基底材料表面形成本发明所述涂层，在真空烘箱100℃干燥1天。
实施例5含没食子酸结构超支化聚氨酯结构集成型涂层应用金属基底
在85℃下，将2.3g没食子酸、12.4g异佛尔酮二异氰酸酯和0.05g二月桂酸二丁基锡置于三口瓶中，机械搅拌，通氮气及冷凝回流，反应2h，温度设置为5℃，将含有二乙醇胺0.001g的N,N二甲基甲酰胺溶液通过蠕动泵滴加到上述溶液中，反应1h，得到没食子酸结构超支化聚氨酯，其支化度为0.52。
将得到的没食子酸结构超支化聚氨酯溶解于质量分数为10％的N,N二甲基甲酰胺，以金属钛合金(TA1ELI)为基底，将基底材料置于没食子酸结构超支化聚氨酯溶液中溶胀10min，取出置于溶有2g分子量为40000Da的聚乙烯吡咯烷酮、0.7g分子量为200Da的聚乙二醇和0.2g钛酸四丁酯的水-乙醇(7:3)溶液中10min，取出置于10mL含有分子量为100000Da的肝素钠0.1g的水溶液中10min，在金属钛合金(TA1ELI)表面形成本发明所述涂层，在真空烘箱100℃干燥1天。
实施例6含没食子酸结构超支化聚氨酯结构集成型涂层应用陶瓷基底
在85℃下，将2.3g没食子酸、12.4g异佛尔酮二异氰酸酯和0.05g的二月桂酸二丁基锡置于三口瓶中，机械搅拌，通氮气及冷凝回流，反应2h，温度设置为5℃，将含有二乙醇胺0.001g的N,N二甲基甲酰胺溶液通过蠕动泵滴加到上述溶液中，反应1h，得到没食子酸结构超支化聚氨酯，其支化度为0.52。
将得到的没食子酸结构超支化聚氨酯溶解于N,N二甲基甲酰胺质量分数10％，以羟基磷酸钙(DTD)为基底，将基底材料置于没食子酸结构超支化聚氨酯溶液中溶胀10min，取出置于溶有2g分子量为40000Da的聚乙烯吡咯烷酮、0.7g分子量为200Da的聚乙二醇和0.2g钛酸四丁酯的水-乙醇(7:3)溶液中10min，取出置于10mL含有分子量为100000Da的肝素钠0.1g的水溶液中10min，在羟基磷酸钙(DTD)表面形成本发明所述涂层，在真空烘箱100℃干燥1天。
以上所述，仅为本发明较佳的具体实施方式，但本发明的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本发明揭露的技术范围内，根据本发明的技术方案及其发明构思加以等同替换或改变，都应涵盖在本发明的保护范围之内。
Claims (10)
1.一种涂层组合物，包括以下质量百分含量的组分：
5wt％～30wt％超支化聚氨酯；
5wt％～30wt％生物相容性聚合物；
0.5wt％～30wt％抗炎药物；
0.01wt％～2wt％粘附性促进剂。
2.根据权利要求1所述的涂层组合物，其特征在于，所述超支化聚氨酯选自没食子酸结构超支化聚氨酯、三羟基苯甲酸酯香豆素结构超支化聚氨酯、白藜芦醇结构超支化聚氨酯、三羟基喹啉结构超支化聚氨酯中的至少一种。
3.根据权利要求2所述的涂层组合物，其特征在于，所述超支化聚氨酯选自没食子酸结构超支化聚氨酯，所述超支化聚氨酯由没食子酸、异佛尔酮二异氰酸酯和二羟基单体制备得到；
或者，
所述超支化聚氨酯选自三羟基苯甲酸酯香豆素结构超支化聚氨酯，所述超支化聚氨酯由三羟基苯甲酸酯香豆素、异佛尔酮二异氰酸酯和二羟基单体制备得到；
或者；
所述超支化聚氨酯选自白藜芦醇结构超支化聚氨酯，所述超支化聚氨酯由白藜芦醇、异佛尔酮二异氰酸酯和二羟基单体制备得到；
或者，
所述超支化聚氨酯选自三羟基喹啉单体结构超支化聚氨酯，所述超支化聚氨酯由三羟基喹啉、异佛尔酮二异氰酸酯和二羟基单体制备得到；
所述二羟基单体选自羧基双酚、酚酞啉、二羟甲基丙酸、乙二醇或二乙醇胺中的至少一种。
4.根据权利要求3所述的涂层组合物，其特征在于，所述超支化聚氨酯的支化度为0.3～0.7。
5.根据权利要求4所述的涂层组合物，所述生物相容性聚合物选自聚乙烯吡咯烷酮、聚乙烯己内酰胺、聚乙二醇、聚己内酯，聚氨酯、肝素类聚合物中的至少一种；
所述抗炎药物选自乙酰水杨酸盐类抗炎药、非乙酰基水杨酸盐类抗炎药、非水杨酸类抗炎药中的至少一种；
所述粘附性促进剂选自钛酸酯类粘附性促进剂、硅烷类粘附性促进剂、铬络合物类粘附性促进剂中的至少一种。
6.一种涂层，由权利要求1～5中任一所述的涂层组合物形成。
7.一种如权利要求6所述的涂层的制备方法，包括：
将基体材料置于所述超支化聚氨酯的溶液中溶胀，溶胀后置于所述生物相容性聚合物、抗炎药物和粘附性促进剂的溶液中继续溶胀，溶胀后进行交联反应，在所述基体材料表面形成所述涂层。
8.根据权利要求7所述的制备方法，其特征在于，所述溶胀的时间为10min～60min；
所述反应的温度为60℃～150℃；所述反应的时间为10h～40h。
9.一种医疗器械，其特征在于，包括基体材料和设置在所述基体材料表面上的涂层；
所述涂层由权利要求1～5中任一所述的涂层组合物形成。
10.根据权利要求9所述的医疗器械，其特征在于，所述基体材料选自金属基体材料、无机非金属基体材料或聚合物基体材料。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211047723.8A CN115337472B (zh) | 2022-08-30 | 2022-08-30 | 一种涂层组合物、涂层及其制备方法、医疗器械 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211047723.8A CN115337472B (zh) | 2022-08-30 | 2022-08-30 | 一种涂层组合物、涂层及其制备方法、医疗器械 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115337472A true CN115337472A (zh) | 2022-11-15 |
| CN115337472B CN115337472B (zh) | 2023-08-29 |
Family
ID=83954054
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211047723.8A Active CN115337472B (zh) | 2022-08-30 | 2022-08-30 | 一种涂层组合物、涂层及其制备方法、医疗器械 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115337472B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116236625A (zh) * | 2023-05-05 | 2023-06-09 | 中科瑞鸿(长春)医疗技术有限公司 | 一种涂层组合物、涂层及其制备方法和医疗器械 |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002100355A1 (en) * | 2001-06-12 | 2002-12-19 | Stick Tech Oy | A prepreg, a composite and their uses |
| CN101977639A (zh) * | 2008-03-20 | 2011-02-16 | 拜尔材料科学股份公司 | 具有亲水涂层的医疗器械 |
| CN102056993A (zh) * | 2008-06-13 | 2011-05-11 | 埃西勒国际通用光学公司 | 与随后涂层和相应涂覆基材具有良好附着性的可光固化丙烯酸系涂料组合物 |
| US20120095112A1 (en) * | 2009-06-22 | 2012-04-19 | Unilever House | Branched polymer dispersants |
| CN103333484A (zh) * | 2013-07-18 | 2013-10-02 | 威海洁瑞医用制品有限公司 | 一种疏水型医用热塑性聚氨酯合金 |
| WO2015044509A1 (en) * | 2013-09-27 | 2015-04-02 | Skulle Implants Oy | A method for coating and a coated surface, a coating and an implant containing such coating |
| CN105983137A (zh) * | 2015-02-11 | 2016-10-05 | 北京迪玛克医药科技有限公司 | 一种超支化聚酯改性聚氨酯医用介入导管及其制备方法 |
| CN106967206A (zh) * | 2017-04-12 | 2017-07-21 | 沈坤 | 亲水润滑医用聚氨酯材料及其制备方法和应用 |
| CN107789677A (zh) * | 2017-09-29 | 2018-03-13 | 湖北大学 | 一种超支化聚酰亚胺抗凝血抗菌材料的制备方法及应用 |
| CN110891620A (zh) * | 2017-05-30 | 2020-03-17 | 赢创加拿大公司 | 具有改性表面的人工瓣膜 |
| CN111407930A (zh) * | 2020-03-19 | 2020-07-14 | 中国科学院长春应用化学研究所 | 一种聚合物仿生涂层及其制备方法 |
| CN113507924A (zh) * | 2019-03-01 | 2021-10-15 | 北卡罗来纳大学教堂山分校 | 通过官能化介孔二氧化硅纳米颗粒的一氧化氮延长释放型聚合物 |
-
2022
- 2022-08-30 CN CN202211047723.8A patent/CN115337472B/zh active Active
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002100355A1 (en) * | 2001-06-12 | 2002-12-19 | Stick Tech Oy | A prepreg, a composite and their uses |
| CN101977639A (zh) * | 2008-03-20 | 2011-02-16 | 拜尔材料科学股份公司 | 具有亲水涂层的医疗器械 |
| CN102056993A (zh) * | 2008-06-13 | 2011-05-11 | 埃西勒国际通用光学公司 | 与随后涂层和相应涂覆基材具有良好附着性的可光固化丙烯酸系涂料组合物 |
| US20120095112A1 (en) * | 2009-06-22 | 2012-04-19 | Unilever House | Branched polymer dispersants |
| CN103333484A (zh) * | 2013-07-18 | 2013-10-02 | 威海洁瑞医用制品有限公司 | 一种疏水型医用热塑性聚氨酯合金 |
| WO2015044509A1 (en) * | 2013-09-27 | 2015-04-02 | Skulle Implants Oy | A method for coating and a coated surface, a coating and an implant containing such coating |
| CN105983137A (zh) * | 2015-02-11 | 2016-10-05 | 北京迪玛克医药科技有限公司 | 一种超支化聚酯改性聚氨酯医用介入导管及其制备方法 |
| CN106967206A (zh) * | 2017-04-12 | 2017-07-21 | 沈坤 | 亲水润滑医用聚氨酯材料及其制备方法和应用 |
| CN110891620A (zh) * | 2017-05-30 | 2020-03-17 | 赢创加拿大公司 | 具有改性表面的人工瓣膜 |
| CN107789677A (zh) * | 2017-09-29 | 2018-03-13 | 湖北大学 | 一种超支化聚酰亚胺抗凝血抗菌材料的制备方法及应用 |
| CN113507924A (zh) * | 2019-03-01 | 2021-10-15 | 北卡罗来纳大学教堂山分校 | 通过官能化介孔二氧化硅纳米颗粒的一氧化氮延长释放型聚合物 |
| CN111407930A (zh) * | 2020-03-19 | 2020-07-14 | 中国科学院长春应用化学研究所 | 一种聚合物仿生涂层及其制备方法 |
Non-Patent Citations (2)
| Title |
|---|
| 孙昭艳等: "高性能高分子材料高性能高分子材料:从基础走向应用", 《科技导报》 * |
| 孙昭艳等: "高性能高分子材料高性能高分子材料:从基础走向应用", 《科技导报》, vol. 35, no. 11, 13 June 2017 (2017-06-13) * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116236625A (zh) * | 2023-05-05 | 2023-06-09 | 中科瑞鸿(长春)医疗技术有限公司 | 一种涂层组合物、涂层及其制备方法和医疗器械 |
| CN116236625B (zh) * | 2023-05-05 | 2024-04-30 | 中科瑞鸿(长春)医疗技术有限公司 | 一种涂层组合物、涂层及其制备方法和医疗器械 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115337472B (zh) | 2023-08-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Hong et al. | Synthesis, characterization, and paclitaxel release from a biodegradable, elastomeric, poly (ester urethane) urea bearing phosphorylcholine groups for reduced thrombogenicity | |
| Ye et al. | Nonthrombogenic, biodegradable elastomeric polyurethanes with variable sulfobetaine content | |
| Yang et al. | Polydopamine modified TiO2 nanotube arrays for long-term controlled elution of bivalirudin and improved hemocompatibility | |
| Thierry et al. | Bioactive coatings of endovascular stents based on polyelectrolyte multilayers | |
| CN101862233B (zh) | 药物释放型血管内支架和治疗再狭窄的方法 | |
| CA2600711C (en) | Compliant polymeric coatings for insertable medical articles | |
| US20160375180A1 (en) | Method for producing medical device and medical device | |
| Bil et al. | Design and in vitro evaluation of electrospun shape memory polyurethanes for self-fitting tissue engineering grafts and drug delivery systems | |
| US8709465B2 (en) | Diazeniumdiolated phosphorylcholine polymers for nitric oxide release | |
| US20020188037A1 (en) | Method and system for providing bioactive agent release coating | |
| EP1551469B1 (en) | Bioactive agent release coating with aromatic poly(meth)acrylates | |
| Ye et al. | Biodegradable zwitterionic polymer coatings for magnesium alloy stents | |
| Ding et al. | Peptide‐Functionalized Polyurethane Coatings Prepared via Grafting‐To Strategy to Selectively Promote Endothelialization | |
| EP1536846A1 (en) | Active agent delivery system including a polyurethane, medical device, and method | |
| TW201019917A (en) | Stent coatings for reducing late stent thrombosis | |
| CN105833358B (zh) | 一种颅内药物洗脱支架系统及其制备方法 | |
| US7041308B2 (en) | Drug-polymer coated stents with segmented homochain copolyesters | |
| CN115337472A (zh) | 一种涂层组合物、涂层及其制备方法、医疗器械 | |
| Liu et al. | Stabilized hemocompatible coating of nitinol devices based on photo-cross-linked alginate/heparin multilayer | |
| JP2012510301A (ja) | 血管壁臨時骨格（補助材）用の生分解性ブレンド | |
| Wang et al. | Nitric oxide-releasing semi-crystalline thermoplastic polymers: preparation, characterization and application to devise anti-inflammatory and bactericidal implants | |
| Yu et al. | A tough, slippery, and anticoagulant double-network hydrogel coating | |
| JPH07100744B2 (ja) | 湿潤時に表面が潤滑性を有する医療用具およびその製造方法 | |
| US20200384149A1 (en) | Absorbable Iron-Based Instrument | |
| Zhou et al. | Adhesive and self-healing polyurethanes with tunable multifunctionality |
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 |