CN115317658A - 一种抗菌凝胶及其制备方法和应用 - Google Patents
一种抗菌凝胶及其制备方法和应用 Download PDFInfo
- Publication number
- CN115317658A CN115317658A CN202210926019.3A CN202210926019A CN115317658A CN 115317658 A CN115317658 A CN 115317658A CN 202210926019 A CN202210926019 A CN 202210926019A CN 115317658 A CN115317658 A CN 115317658A
- Authority
- CN
- China
- Prior art keywords
- polymer solution
- gel
- polyphenol
- zwitterionic
- ferric
- 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.)
- Pending
Links
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 238000001879 gelation Methods 0.000 title description 2
- 239000000843 powder Substances 0.000 claims abstract description 64
- 229920000642 polymer Polymers 0.000 claims abstract description 54
- 235000013824 polyphenols Nutrition 0.000 claims abstract description 44
- 150000008442 polyphenolic compounds Chemical class 0.000 claims abstract description 38
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910001447 ferric ion Inorganic materials 0.000 claims abstract description 15
- 238000002156 mixing Methods 0.000 claims abstract description 8
- 239000000243 solution Substances 0.000 claims description 65
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
- 239000000178 monomer Substances 0.000 claims description 27
- -1 quaternary ammonium salt cation Chemical class 0.000 claims description 25
- 239000011787 zinc oxide Substances 0.000 claims description 18
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 16
- 239000003999 initiator Substances 0.000 claims description 11
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims description 8
- 238000006116 polymerization reaction Methods 0.000 claims description 8
- QAIPRVGONGVQAS-DUXPYHPUSA-N trans-caffeic acid Chemical compound OC(=O)\C=C\C1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-DUXPYHPUSA-N 0.000 claims description 8
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 claims description 7
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 claims description 6
- 229920005615 natural polymer Polymers 0.000 claims description 6
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 6
- 239000000565 sealant Substances 0.000 claims description 6
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 claims description 5
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 claims description 5
- 239000001263 FEMA 3042 Substances 0.000 claims description 5
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 claims description 5
- 230000009471 action Effects 0.000 claims description 5
- 239000012670 alkaline solution Substances 0.000 claims description 5
- 229920005610 lignin Polymers 0.000 claims description 5
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 claims description 5
- 229920002258 tannic acid Polymers 0.000 claims description 5
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 claims description 5
- 235000015523 tannic acid Nutrition 0.000 claims description 5
- 229940033123 tannic acid Drugs 0.000 claims description 5
- ACEAELOMUCBPJP-UHFFFAOYSA-N (E)-3,4,5-trihydroxycinnamic acid Natural products OC(=O)C=CC1=CC(O)=C(O)C(O)=C1 ACEAELOMUCBPJP-UHFFFAOYSA-N 0.000 claims description 4
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 4
- 229940074360 caffeic acid Drugs 0.000 claims description 4
- 235000004883 caffeic acid Nutrition 0.000 claims description 4
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 claims description 4
- 235000005487 catechin Nutrition 0.000 claims description 4
- 229950001002 cianidanol Drugs 0.000 claims description 4
- QAIPRVGONGVQAS-UHFFFAOYSA-N cis-caffeic acid Natural products OC(=O)C=CC1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-UHFFFAOYSA-N 0.000 claims description 4
- 235000004515 gallic acid Nutrition 0.000 claims description 4
- 229940074391 gallic acid Drugs 0.000 claims description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-O Imidazolium Chemical compound C1=C[NH+]=CN1 RAXXELZNTBOGNW-UHFFFAOYSA-O 0.000 claims description 3
- 229920001732 Lignosulfonate Polymers 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 125000000129 anionic group Chemical group 0.000 claims description 3
- PFTAWBLQPZVEMU-UHFFFAOYSA-N catechin Chemical compound OC1CC2=C(O)C=C(O)C=C2OC1C1=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-UHFFFAOYSA-N 0.000 claims description 3
- 125000002091 cationic group Chemical group 0.000 claims description 3
- RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 claims description 3
- 229910000360 iron(III) sulfate Inorganic materials 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 230000000379 polymerizing effect Effects 0.000 claims description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 230000000845 anti-microbial effect Effects 0.000 claims 6
- 239000004599 antimicrobial Substances 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 15
- 238000011065 in-situ storage Methods 0.000 abstract description 14
- 230000017423 tissue regeneration Effects 0.000 abstract description 4
- 210000004369 blood Anatomy 0.000 abstract description 2
- 239000008280 blood Substances 0.000 abstract description 2
- 239000012530 fluid Substances 0.000 abstract description 2
- 239000000499 gel Substances 0.000 description 75
- 239000000017 hydrogel Substances 0.000 description 35
- 239000000853 adhesive Substances 0.000 description 28
- 230000001070 adhesive effect Effects 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 238000003756 stirring Methods 0.000 description 21
- 206010052428 Wound Diseases 0.000 description 17
- 208000027418 Wounds and injury Diseases 0.000 description 17
- 210000001519 tissue Anatomy 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 12
- 210000003491 skin Anatomy 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- 239000008367 deionised water Substances 0.000 description 10
- 229910021641 deionized water Inorganic materials 0.000 description 10
- 238000000227 grinding Methods 0.000 description 9
- 238000007873 sieving Methods 0.000 description 9
- 238000002791 soaking Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 238000004108 freeze drying Methods 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 150000003384 small molecules Chemical class 0.000 description 7
- 238000009210 therapy by ultrasound Methods 0.000 description 7
- 230000001580 bacterial effect Effects 0.000 description 6
- 229940117986 sulfobetaine Drugs 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- GPLIMIJPIZGPIF-UHFFFAOYSA-N 2-hydroxy-1,4-benzoquinone Chemical compound OC1=CC(=O)C=CC1=O GPLIMIJPIZGPIF-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
- 206010072170 Skin wound Diseases 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 229960003237 betaine Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 229920002521 macromolecule Polymers 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000003825 pressing Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 230000029663 wound healing Effects 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical group O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 231100000263 cytotoxicity test Toxicity 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 230000023597 hemostasis Effects 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000009851 immunogenic response Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229920002006 poly(N-vinylimidazole) polymer Polymers 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- 238000009864 tensile test Methods 0.000 description 2
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 1
- LYLDIIUFTYRPPK-UHFFFAOYSA-N 1h-imidazole-2-sulfonic acid Chemical compound OS(=O)(=O)C1=NC=CN1 LYLDIIUFTYRPPK-UHFFFAOYSA-N 0.000 description 1
- 241001391944 Commicarpus scandens Species 0.000 description 1
- 229920001651 Cyanoacrylate Polymers 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010080379 Fibrin Tissue Adhesive Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- MWCLLHOVUTZFKS-UHFFFAOYSA-N Methyl cyanoacrylate Chemical compound COC(=O)C(=C)C#N MWCLLHOVUTZFKS-UHFFFAOYSA-N 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000031737 Tissue Adhesions Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 238000001949 anaesthesia Methods 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000010952 in-situ formation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- YCIMNLLNPGFGHC-UHFFFAOYSA-N o-dihydroxy-benzene Natural products OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000033116 oxidation-reduction process Effects 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 230000021715 photosynthesis, light harvesting Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229940083025 silver preparation Drugs 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003106 tissue adhesive Substances 0.000 description 1
- 229940075469 tissue adhesives Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0015—Medicaments; Biocides
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/02—Surgical adhesives or cements; Adhesives for colostomy devices containing inorganic 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
-
- 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
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
-
- 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
- A61L2300/40—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
- A61L2300/45—Mixtures of two or more drugs, e.g. synergistic mixtures
-
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Surgery (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
本发明公开了一种抗菌凝胶及其制备方法和应用,涉及生物医用材料技术领域,该抗菌凝胶包括以下步骤:将多酚高分子溶液、三价铁离子以及两性离子聚合物溶液混合。此凝胶粉末可直接作用于湿润表面,吸收界面水分或组织液、血液后能快速原位成型并牢固粘附,能迅速闭合伤口及促进组织再生,具备抗菌功效,可长期保存。
Description
技术领域
本发明属于生物医用材料技术领域,涉及一种抗菌凝胶及其制备方法和应用。
背景技术
医用粘合敷料具有使用简便、无需二次手术或频繁换药、对组织损伤较小等优点,能减轻患者疼痛、缩短病程,因此逐步取代了缝线、铆钉和夹具等传统的缝合用具,而在临床上被广泛应用于组织的快速固定和粘合。随着生物医用材料的发展,目前已有多种商业化的组织粘合剂能用于伤口封闭及止血,包括氰基丙烯酸酯类、纤维蛋白粘胶类、明胶类等医用粘合剂。但这些粘合剂其具有细胞毒性或引起免疫原性反应,在湿润环境中粘合强度不足,且缺乏抗菌等生物功能性,因此需要改进。
以水凝胶为代表的湿性粘合敷料有助于维持伤口湿润环境,避免伤口粘连和结痂;其类细胞外基质的三维微环境有助于细胞迁移分化,有效促进组织修复。但是,水凝胶在湿润环境下机械强度弱,粘合强度低,需要长时间外加力实现粘合,不利于临床使用。而且水凝胶难以长期保存,在湿润环境中易被细菌和微生物污染,增加了其应用成本及难度。
在湿润环境中,环境及水凝胶中的水分子对粘合强度及稳定性有较大影响,主要原因为:1、界面水层阻碍了粘附性聚合物与基底的直接接触;2、粘合性分子与水分子通过氢键等作用结合,弱化了其与基底的相互作用;3、水凝胶在水中溶胀导致内聚力减小,网络机械性能下降,易被破坏造成脱粘附。传统水凝胶网络结构中含有大量水分子,分子间结合力弱,且交联高分子结构限制了分子链向粘合基底接触和扩散;且传统高分子粘合剂成型或固化过程会产生热量,可能对组织造成二次伤害;固化反应的催化剂及副产物具有细胞毒性,不利于其作为医用粘合剂的应用。
目前多采用儿茶酚类化合物改性或直接共混方法提升湿润环境中的粘合强度,但是此类方法易受氧化及pH影响,并存在由改性或共聚反应中残留的小分子和有机溶剂引起的生理毒性问题,此外,单一儿茶酚粘附机制的凝胶材料在湿润环境中长期粘合稳定性和粘合强度较差,这限制了其在组织工程尤其是粘合湿性创面中的应用。
因此目前的水凝胶存在以下问题需要改进:具有细胞毒性或免疫原性反应,在湿润环境中粘合强度不足,易受氧化及pH影响而难以实现长期稳定粘附,且缺乏抗菌等生物功能性,难以长期保存的问题。
发明内容
为解决上述技术问题,本发明提供一种抗菌凝胶及其制备方法和应用。
本发明是这样实现的,一种抗菌凝胶,包括多酚高分子溶液、三价铁离子以及两性离子聚合物溶液混合制成的产物。
进一步地,所述抗菌凝胶为粉末状。
进一步地,所述抗菌凝胶的目数为50-1600目。
本发明还提供一种如上述的抗菌凝胶的制备方法,包括以下步骤:
将所述多酚高分子溶液、所述三价铁离子以及所述两性离子聚合物溶液混合。
进一步地,所述两性离子聚合物溶液的制备步骤为:将两性离子单体加入纯水后在纳米氧化锌和引发剂作用下,聚合得到两性离子聚合物溶液;所述多酚天然高分子的制备步骤为:将多酚天然高分子溶解在碱性溶液中,得到所述多酚高分子溶液。
进一步地,所述两性离子单体中的阳离子基团为季铵盐阳离子、季膦盐阳离子、吡啶鎓离子和咪唑鎓离子中的任意一种,所述两性离子单体中的阴离子基团为磺酸根阴离子、羧酸根阴离子和磷酸根阴离子中的任意一种。
进一步地,所述两性离子单体加入纯水后的质量浓度为0.1g/ml-0.6g/ml,所述两性离子单体、纳米氧化锌和引发剂的质量比为100:(0.1-1.5):(0.1-1.5),所述引发剂为过硫酸铵、过硫酸钾和过硫酸钠的任意一种,所述聚合的温度为15-70℃,反应时间为0.5-24h。
进一步地,所述多酚高分子为单宁酸、木质素、木质素磺酸盐、咖啡酸、儿茶素和没食子酸的任意一种,所述多酚高分子溶液的质量浓度为0.01g/ml-0.40g/ml,所述多酚高分子溶液的pH>7。
进一步地,所述三价铁离子为氯化铁、硝酸铁或硫酸铁,所述三价铁离子的质量与多酚高分子溶液的体积比为0.1%-1.5%,所述多酚高分子溶液与两性离子聚合物溶液体积比为(1:20)-(1:1)。
本发明还提供一种医用敷料或密封剂,所述医用辅料或密封剂包括上述的原位成型的抗菌粘附性凝胶粉末。
与现有技术相比,本发明的有益效果表现为:
1、本发明制备的抗菌凝胶及凝胶粉末成型后均形成稳定的动态交联网络,具有良好的力学性能,其动态可逆相互作用有利于能量耗散,使凝胶表现出良好的韧性及回弹性,能匹配软组织及皮肤的力学性能,避免受力后结构破坏而脱粘附;
2、本发明制备的抗菌凝胶粉末具备快速原位吸湿成型特性,在针对不同材料(工程材料及组织)界面实现快速高强度粘附,过程没有发热和副反应发生,避免对细胞及组织的二次损害;
3、本发明制备的凝胶粉末成型后在湿润环境表现出良好的粘附性能,且具有良好的生物相容性和低细胞毒性,对组织无刺激性,适用于各种湿润组织界面的粘附;
4、本发明制备的抗菌凝胶及凝胶粉末均具备抗菌性能,作为皮肤创口愈合敷料可抑制炎症,改善组织愈合效果;
5、本发明制备的凝胶粉末与同类型产品相比,合成工艺简单,能长期储存而不影响实际粘合效果,直接涂抹应用便利,无需额外的按压,使用时无需聚合或固化,易于操作,具有良好的实际应用前景。
附图说明
图1为本发明的凝胶粉末在湿润组织创面原位成型及形成粘合的机理示意图;
图2为本发明制备的凝胶粉末吸湿原位成型及其粘附皮肤的图片展示;
图3为本发明制备的凝胶粉末在研磨成粉末前及吸水成胶后的拉伸性能结果;
图4为本发明制备的凝胶粉末在各种材料湿润界面上的粘合强度测试结果;
图5为本发明制备的凝胶对不同基底材料的粘附效果图;
图6为本发明制备的凝胶粉末对金黄葡萄糖球菌和大肠杆菌的抗菌率结果图;
图7为本发明制备的凝胶粉末的细胞毒性测试结果;
图8为本发明制备的凝胶粉末对SD大鼠皮肤伤口的闭合效率统计图。
具体实施方式
为了使本发明要解决的技术问题、技术方案及有益效果更加清楚明白,以下结合附图及实施例,对本发明进行进一步详细说明。应当理解,此处所描述的具体实施例仅仅用以解释本发明,并不用于限定本发明。
本发明的实施例提供一种抗菌凝胶,由多酚高分子溶液、三价铁离子以及两性离子聚合物溶液混合制成的产物。
其中,两性离子单体具有强吸湿性,结构中含有阳离子基团和阴离子基团,相反电荷基团间存在偶极作用,制得的水凝胶粉末利用其强吸湿性和偶极作用,能吸附界面水溶胀并快速原位成型形成初步粘合,成型基于动态非共价的电荷作用力,避免了传统粘合剂在创面或伤口处原位固化时反应放热或副产物对组织和细胞的伤害,且原位成型的同时吸附界面水,有利于粘附性高分子在基底界面渗透,从而降低界面能,改善与界面基质的接触效率,有利于提高在湿润界面上的粘合强度。
将多酚高分子溶液、三价铁离子以及两性离子聚合物溶液共混,其中,三价铁离子与多酚高分子之间形成稳定且可逆的配位,伴随三价铁-二价铁的电子转移,其可促进多酚高分子酚羟基-苯醌转换,从而形成酚羟基-苯醌以及三价铁-二价铁的氧化还原的动态平衡体系,改善了水凝胶柔韧性及可自修复性能,提升了其在湿润环境中的粘合强度及力学稳定性,在粘附成型后,两性离子聚合物间的偶极作用与多酚高分子间可逆的配位键、氢键、静电力等非共价作用力形成可逆动态交联网络,进一步强化粘合部位的力学强度和粘合强度,使凝胶不受环境水的影响,形成稳定粘附并保持韧性,解决了传统粘合性水凝胶韧性差、易碎、在湿润环境中易脱粘附等问题。
其中,加入的三价铁离子与铜、镁、锌等常用金属配位离子相比,与多酚高分子的配位键强度更高,更易形成稳定的凝胶网络,而纳米银虽有相似的机理,但纳米银制备步骤更为繁琐,且具有生物毒性,而三价铁离子则不具有上述的缺点。
具体地,所述抗菌凝胶为粉末状,经透析、冷冻干燥、研磨过筛而制得,此粉末使用时直接涂抹或施加至对应部位即可,应用便利,无需额外的按压,使用时无需聚合或固化,易于操作,具有良好的实际应用前景。
具体地,所述抗菌凝胶的目数(即过筛的目数)为50-1600目,合适的过筛目数的水凝胶粉末使其具有合适的吸湿速率,吸附界面的水或血液、组织液等液体的同时原位成型而粘合。
本发明实施例还提供一种如上述的抗菌凝胶的制备方法,包括以下步骤:
将所述多酚高分子溶液、所述三价铁离子以及所述两性离子聚合物溶液混合。
具体地,所述两性离子聚合物溶液的制备步骤为:将两性离子单体加入纯水后在纳米氧化锌和引发剂作用下,聚合得到两性离子聚合物溶液;所述多酚天然高分子的制备步骤为:将多酚天然高分子溶解在碱性溶液中,得到所述多酚高分子溶液。
其中,加入的纳米氧化锌本身是一种催化剂,不仅能加速两性离子单体聚合成两性离子聚合物,而且起到一定的抗菌和生物活性作用,改善水凝胶的抗菌性能;而作为一种应用广泛的抗菌功能性纳米颗粒,纳米氧化锌与铜、银等抗菌性金属相比细胞毒性较低,更适用于医用粘合敷料;且纳米氧化锌和引发剂(过硫酸铵、过硫酸钾和过硫酸钠)一起使用时,会大大缩短两性离子单体聚合的时间;除了纳米氧化锌之外,金纳米粒子也具有加速两性离子单体聚合和抗菌的作用。加入的多酚高分子的生物活性能抑制伤口炎症,起到止血和促组织再生的功能,加入的多酚类高分子与纳米氧化锌协同作用,进一步协同提高水凝胶的抗菌性能,有利于抑制伤口炎症,加速伤口愈合。
其中,多酚高分子加入碱性溶液中溶解,碱性溶液可为浓度为1.0%至5.0%的氢氧化钠溶液,天然多酚化合物一般在碱性条件下溶解,且碱性条件下更易使酚羟基氧化为苯醌结构,有利于形成上述的动态平衡体系。
具体地,所述两性离子单体中的阳离子基团为季铵盐阳离子、季膦盐阳离子、吡啶鎓离子和咪唑鎓离子中的任意一种,所述两性离子单体中的阴离子基团为磺酸根阴离子、羧酸根阴离子和磷酸根阴离子中的任意一种。
具体地,所述两性离子单体为甲基丙烯酰乙基磺基甜菜碱、聚(3-二甲基甲基-丙烯酰氧乙基丙烷磺酸铵)或聚乙烯基咪唑磺酸甜菜碱。
具体地,所述两性离子单体加入纯水后的质量浓度为0.1g/ml-0.6g/ml,所述两性离子单体、纳米氧化锌和引发剂的质量比为100:(0.1-1.5):(0.1-1.5),优选地,加入的两性离子单体和引发剂的质量比为100:(0.40-1.25)。
具体地,所述引发剂为过硫酸铵、过硫酸钾和过硫酸钠的任意一种,所述聚合的温度为15-70℃,反应时间为0.5-24h,
具体地,所述多酚高分子为单宁酸、木质素、木质素磺酸盐、咖啡酸、儿茶素和没食子酸的任意一种,所述多酚高分子溶液质量浓度为0.01g/ml-0.40g/ml,所述多酚高分子溶液的pH>7,碱性条件下更易使酚羟基氧化为苯醌结构,有利于形成上述的动态平衡体系。
具体地,所述三价铁离子为氯化铁、硝酸铁或硫酸铁,所述三价铁离子的质量与多酚高分子溶液的体积比为0.1%-1.5%,在此范围下更易形成酚羟基-苯醌以及三价铁-二价铁的氧化还原的动态平衡体系,所述多酚高分子溶液与两性离子聚合物溶液体积比为(1:20)-(1:1),在此范围下,多酚高分子溶液与两性离子聚合物溶液共混后更易形成稳定且可逆的动态交联网络。
本发明另一实施例还提供一种医用敷料或密封剂,所述医用辅料或密封剂包括上述的原位成型的抗菌粘附性凝胶粉末。
具体地,所述医用辅料或医用密封剂可用于快速止血、组织粘合、组织固定和医疗器械与组织间的固定;所述组织为皮肤、肌肉、内脏中的任意一种。
以下结合具体实施例对本发明的技术方案做进一步说明。
实施例1
1.将4g甲基丙烯酰乙基磺基甜菜碱溶解在10ml纯水中,加入0.05g纳米氧化锌,充分搅拌并超声处理10min;加入20mg过硫酸铵,充分搅拌均匀后,25℃反应2h,得到聚合物溶液;
2.将0.1g木质素溶解在10ml氢氧化钠溶液中,加入0.05g三氯化铁,充分搅拌溶解后加入步骤1制得的溶液中,得到水凝胶;
3.将所得水凝胶浸泡于去离子水中纯化72小时,去除未反应单体和小分子,并冷冻干燥;
4.将步骤3中干燥的凝胶研磨成粉并过100目筛,得到凝胶粉末。
实施例2
1.将5g甲基丙烯酰乙基磺基甜菜碱溶解在15ml纯水中,加入0.02g纳米氧化锌,充分搅拌并超声处理10min;加入30mg过硫酸钾,充分搅拌均匀后,37℃反应8h,得到聚合物溶液;
2.将0.2g儿茶素溶解在5ml氢氧化钠溶液中,加入0.01g三氯化铁,充分搅拌溶解后加入步骤1制得的溶液中,得到水凝胶;
3.将所得水凝胶浸泡于去离子水中纯化72小时,去除未反应单体和小分子,并冷冻干燥;
4.将步骤3中干燥的凝胶研磨成粉并过200目筛,得到凝胶粉末。
实施例3
1.将2g甲基丙烯酸羧酸甜菜碱溶解在10ml纯水中,加入0.02g纳米氧化锌,充分搅拌并超声处理10min;加入30mg过硫酸钾,充分搅拌均匀后,70℃反应1h,得到聚合物溶液;
2.将0.2g单宁酸溶解在2ml氢氧化钠溶液中,加入0.03g三氯化铁,充分搅拌溶解后加入步骤1制得的溶液中,得到水凝胶;
3.将所得水凝胶浸泡于去离子水中纯化48小时,去除未反应单体和小分子,并冷冻干燥;
4.将步骤3中干燥的凝胶研磨成粉并过360目筛,得到凝胶粉末。
实施例4
1.将1.2g聚(3-二甲基甲基-丙烯酰氧乙基丙烷磺酸铵)溶解在12ml纯水中,加入0.018g纳米氧化锌,充分搅拌并超声处理5min;加入15mg过硫酸铵,充分搅拌均匀后,25℃反应6h,得到聚合物溶液;
2.将0.5g咖啡酸溶解在5ml氢氧化钠溶液中,加入0.05g三氯化铁,充分搅拌溶解后加入步骤1制得的溶液中,得到水凝胶;
3.将所得水凝胶浸泡于去离子水中纯化72小时,去除未反应单体和小分子,并冷冻干燥;
4.将步骤3中干燥的凝胶研磨成粉并过50目筛,得到凝胶粉末。
实施例5
1.将2g聚乙烯基咪唑磺酸甜菜碱溶解在10ml纯水中,加入0.02g纳米氧化锌,充分搅拌并超声处理15min;加入20mg过硫酸钠,充分搅拌均匀后,室温反应5h,得到聚合物溶液;
2.将0.5g没食子酸酯溶解在5ml氢氧化钠溶液中,加入0.03g三氯化铁,充分搅拌溶解后加入步骤1制得的溶液中,得到水凝胶;
3.将所得水凝胶浸泡于去离子水中纯化72小时,去除未反应单体和小分子,并冷冻干燥;
4.将步骤3中干燥的凝胶研磨成粉并过80目筛,得到凝胶粉末
实施例6
1.将6g甲基丙烯酰乙基磺基甜菜碱溶解在10ml纯水中,加入0.05g纳米氧化锌,充分搅拌并超声处理10min;加入20mg过硫酸铵,充分搅拌均匀后,15℃反应24h,得到聚合物溶液;
2.将4g单宁酸溶解在10ml氢氧化钠溶液中,加入10mg三氯化铁,充分搅拌溶解后加入步骤1制得的溶液中,得到水凝胶;
3.将所得水凝胶浸泡于去离子水中纯化72小时,去除未反应单体和小分子,并冷冻干燥;
4.将步骤3中干燥的凝胶研磨成粉并过100目筛,得到凝胶粉末。
实施例7
1.将8g甲基丙烯酰乙基磺基甜菜碱溶解在20ml纯水中,加入0.008g纳米氧化锌,充分搅拌并超声处理10min;加入8mg过硫酸铵,充分搅拌均匀后,25℃反应12h,得到聚合物溶液;
2.将0.1g木质素溶解在1ml氢氧化钠溶液中,加入0.01g三氯化铁,充分搅拌溶解后加入步骤1制得的溶液中,得到水凝胶;
3.将所得水凝胶浸泡于去离子水中纯化72小时,去除未反应单体和小分子,并冷冻干燥;
4.将步骤3中干燥的凝胶研磨成粉并过1600目筛,得到凝胶粉末。
一、本发明制备的凝胶粉末原位成胶及粘合效果测试:
取实施例1中制备的凝胶粉末100mg,滴加500μl去离子水,结果如图2所示,观察到粉末能通过吸水润涨并重新成胶,并能稳定粘附皮肤组织。
二、本发明制备的凝胶粉末原位成胶前后力学性能对比实验
取实施例2中制备的水凝胶,加工为长30×10×5mm的长方形块体;取实施例2中制备的水凝胶粉末1g,填充于30×10×5mm的长方形模具中,加入1ml去离子水使粉末成胶。对上述两种凝胶样品用万能力学测试平台(Instron5967)进行拉伸测试,移动速度为5mm/min,结果如图3所示。
由图3结果可知,粉末原位成胶后与原水凝胶对比拉伸比及初始模量相近,证明本发明制备的凝胶粉末不仅能通过吸湿润涨重新成型,且成型后力学强度没有明显下降,展现出良好的拉伸率及韧性。
三、本发明制备的凝胶粉末对玻璃、硅胶、塑料、木头、猪皮五种基质的粘合剪切强度测试
将上述五种基质材料分别剪裁为30×10mm的长方形条状,在磷酸盐缓冲液(PBS)中浸泡1h,取出后在两块基质的重叠面积处(10×10mm)涂抹实施例4中制备的凝胶粉末,固定放置30min,用用万能力学测试平台(Instron5967)进行拉伸测试,测量拉开粘结基质材料所需的最大力,移动速度为5mm/min,结果根据重合面积计算粘合剪切最大压强,结果如图4所示。
由图4结果可知,粉末在湿润基质表面表现出良好的粘合强度,证明本发明制备的凝胶粉末能有效粘合不同基质的湿润界面。
四、本发明制备的凝胶粉末对各种工程材料及新鲜组织的粘合效果测试
将工程材料及心、肝、肺、肾、骨、皮肤等组织在PBS中浸泡1h,取实施例1中制备的凝胶粉末100mg,加入500μl去离子水引发成胶,用手指粘附水凝胶,按压侵泡取出的基质,观察凝胶是否能粘附各种湿润基质表面,检测结果如图5所示。
由图5可知,粉末成胶后对各种工程材料及心、肝、肺、肾、骨、皮肤均能表现处良好的粘附效果。
五、本发明制备的凝胶粉末抗菌效果测试
1.将大肠杆菌及金黄葡萄糖球菌分别转移于5ml液体Luria-Bertani(LB)培养基中,37℃摇床培养12h。将增殖后的菌液以10-3、10-4、10-5、10-6、10-7浓度梯度稀释后,用紫外分光光度计检测600nm处菌液吸光度(OD),选择OD为0.2-0.8的稀释浓度进行下一步实验;
2.将步骤1中所选培养液以10-3、10-4、10-5再次稀释,每种菌液取500μl菌液加入24孔板,每孔加入200mg实施例1制备的凝胶样品,并以无样品加入的孔(blank)为对照组,37℃摇床培育12h;
3.将步骤2中共培养后的菌液取100μl涂布于固体LB培养基上,37℃静置培养12h后,对固体培养基上的菌落进行计数。
结果如图6所示,在与本发明制备的凝胶样品共培养后,两种菌液中菌落数与对照组相比大幅下降,证实了凝胶对两种细菌表现出良好的抗菌性能。
六、本发明制备的凝胶粉末细胞毒性测试
选用小鼠成纤维细胞L-929进行细胞实验,细胞用DMEM培养基在培养箱中孵育(37℃,5%CO2)。细胞增殖后,吸除培养基,用PBS洗涤细胞,加入少量胰酶,在培养箱中孵育3min(37℃,5%CO2),取出后加入DMEM培养基1ml,摇匀后,1000rpm离心3min,吸出上清后得到细胞沉淀,加入新的DMEM培养基1ml并吹打均匀,用细胞计数器进行计数后,用上述培养基稀释细胞至浓度5万个/ml。在48孔板中每孔加入上述培养基1ml,放入培养箱(37℃,5%CO2)中24小时至细胞贴壁,显微镜下观察到细胞成纺锤形,每个孔中加入实施例6制备的凝胶200mg,相同条件继续培养1-3天。培养既定时间后取出孔板,每孔加入MTT溶液(5mg/ml)20μL,孵育4小时后吸除培养基,每个孔中加入DMSO溶液100μL。用酶标仪测定492nm波长下每个孔的吸光值(A)。
结果如图7所示,样品孔吸光度与空白孔接近,共培养3天吸光度无明显下降,证明了样品对小鼠成纤维细胞无毒性。
七、凝胶对皮肤伤口原位粘合及促皮肤组织修复效果测试
以SD大鼠(周龄6-8周,性别不限)为实验动物模型。以异氟烷为麻醉剂对大鼠进行吸入麻醉(诱导浓度3%,维持浓度1.5%)。麻醉后将大鼠固定在手术台上,背部剃毛并用酒精及碘伏消毒。用手术刀片在背部制造皮肤全层切口,长度为30mm。用手术镊拉紧伤口两侧皮肤,在伤口处涂抹实施例7制备的凝胶粉末200mg,并用手术镊拉近伤口两侧皮肤维持3min待凝胶成型。用同样操作方法,建立空白对照组(不对伤口进行处理),缝合组(用缝线对伤口进行缝合)以及商用产品(3M凝胶)粘合组作为对照。10天后,对大鼠模型进行安乐死,取下伤口部位皮肤,测量伤口长度。
结果如图8所示,凝胶粘合组伤口长度与商用凝胶组近似,优于缝线组及空白组,证实了本发明凝胶粉末能原位成胶并粘合湿润伤口,最终促进伤口愈合。
以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的原则之内所作的任何修改、等同替换和改进等,均应包含在本发明的保护范围之内。
Claims (10)
1.一种抗菌凝胶,其特征在于,包括多酚高分子溶液、三价铁离子以及两性离子聚合物溶液混合制成的产物。
2.如权利要求1所述的抗菌凝胶,其特征在于,所述抗菌凝胶为粉末状。
3.如权利要求2所述的抗菌凝胶,其特征在于,所述抗菌凝胶的目数为50-1600目。
4.如权利要求1-3中任一项所述的抗菌凝胶的制备方法,其特征在于,包括以下步骤:
将所述多酚高分子溶液、所述三价铁离子以及所述两性离子聚合物溶液混合。
5.如权利要求4所述的制备方法,其特征在于,所述两性离子聚合物溶液的制备步骤为:将两性离子单体加入纯水后在纳米氧化锌和引发剂作用下,聚合得到两性离子聚合物溶液;
和/或,所述多酚天然高分子的制备步骤为:将多酚天然高分子溶解在碱性溶液中,得到所述多酚高分子溶液。
6.如权利要求5所述的制备方法,其特征在于,所述两性离子单体中的阳离子基团为季铵盐阳离子、季膦盐阳离子、吡啶鎓离子和咪唑鎓离子中的任意一种,所述两性离子单体中的阴离子基团为磺酸根阴离子、羧酸根阴离子和磷酸根阴离子中的任意一种。
7.如权利要求5或6所述的制备方法,其特征在于,所述两性离子单体加入纯水后的质量浓度为0.1g/ml-0.6g/ml,所述两性离子单体、纳米氧化锌和引发剂的质量比为100:(0.1-1.5):(0.1-1.5),所述引发剂为过硫酸铵、过硫酸钾和过硫酸钠的任意一种,所述聚合的温度为15-70℃,反应时间为0.5-24h。
8.如权利要求5所述的制备方法,其特征在于,所述多酚高分子为单宁酸、木质素、木质素磺酸盐、咖啡酸、儿茶素和没食子酸的任意一种,所述多酚高分子溶液的质量浓度为0.01g/ml-0.40g/ml,所述多酚高分子溶液的pH>7。
9.如权利要求4所述的制备方法,其特征在于,所述三价铁离子为氯化铁、硝酸铁或硫酸铁,所述三价铁离子的质量与多酚高分子溶液的体积比为0.1%-1.5%,所述多酚高分子溶液与两性离子聚合物溶液体积比为(1:20)-(1:1)。
10.一种医用敷料或密封剂,其特征在于,包括如权利要求1-3中任一项所述的抗菌凝胶。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210926019.3A CN115317658A (zh) | 2022-08-03 | 2022-08-03 | 一种抗菌凝胶及其制备方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210926019.3A CN115317658A (zh) | 2022-08-03 | 2022-08-03 | 一种抗菌凝胶及其制备方法和应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN115317658A true CN115317658A (zh) | 2022-11-11 |
Family
ID=83921733
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210926019.3A Pending CN115317658A (zh) | 2022-08-03 | 2022-08-03 | 一种抗菌凝胶及其制备方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115317658A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116983254A (zh) * | 2023-08-03 | 2023-11-03 | 山东中医药大学 | 一种多酚-甜菊糖苷中药小分子水凝胶及其制备方法和应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015174643A1 (ko) * | 2014-05-15 | 2015-11-19 | 포항공과대학교 산학협력단 | 표면 처리된 나노섬유를 포함하는 하이드로젤 및 이의 제조방법 |
KR20150131951A (ko) * | 2014-05-15 | 2015-11-25 | 포항공과대학교 산학협력단 | 표면 처리된 나노섬유를 포함하는 하이드로젤 및 이의 제조방법 |
CN111821508A (zh) * | 2020-07-15 | 2020-10-27 | 南方医科大学口腔医院 | 一种复合冷冻凝胶及其制备方法和应用 |
CN112094375A (zh) * | 2020-03-12 | 2020-12-18 | 四川大学华西医院 | 一种粘性水凝胶及自粘性医用口罩及其制备方法 |
-
2022
- 2022-08-03 CN CN202210926019.3A patent/CN115317658A/zh active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015174643A1 (ko) * | 2014-05-15 | 2015-11-19 | 포항공과대학교 산학협력단 | 표면 처리된 나노섬유를 포함하는 하이드로젤 및 이의 제조방법 |
KR20150131951A (ko) * | 2014-05-15 | 2015-11-25 | 포항공과대학교 산학협력단 | 표면 처리된 나노섬유를 포함하는 하이드로젤 및 이의 제조방법 |
CN112094375A (zh) * | 2020-03-12 | 2020-12-18 | 四川大学华西医院 | 一种粘性水凝胶及自粘性医用口罩及其制备方法 |
CN111821508A (zh) * | 2020-07-15 | 2020-10-27 | 南方医科大学口腔医院 | 一种复合冷冻凝胶及其制备方法和应用 |
Non-Patent Citations (1)
Title |
---|
JINTAO WANG等: "Antibacterial Zwitterionic Polyelectrolyte Hydrogel Adhesives with Adhesion Strength Mediated by Electrostatic Mismatch", 《ACS APPLIED MATERIALS & INTERFACES》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116983254A (zh) * | 2023-08-03 | 2023-11-03 | 山东中医药大学 | 一种多酚-甜菊糖苷中药小分子水凝胶及其制备方法和应用 |
CN116983254B (zh) * | 2023-08-03 | 2024-02-02 | 山东中医药大学 | 一种多酚-甜菊糖苷中药小分子水凝胶及其制备方法和应用 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Zhang et al. | Polyphenol scaffolds in tissue engineering | |
Lu et al. | Mussel-inspired blue-light-activated cellulose-based adhesive hydrogel with fast gelation, rapid haemostasis and antibacterial property for wound healing | |
CN113577377B (zh) | 一种活性氧消除抗菌消炎水凝胶皮肤敷料及其制备方法 | |
Yao et al. | Design strategies for adhesive hydrogels with natural antibacterial agents as wound dressings: Status and trends | |
CN109331216B (zh) | 一种快速止血水凝胶及其制备方法 | |
CN110448721B (zh) | 一种抗菌粘附导电止血抗氧化的可注射复合水凝胶及其制备方法和应用 | |
CN114404649B (zh) | 一种具有pH/葡萄糖双响应性释放二甲双胍的水凝胶及制备方法和应用 | |
CN105920652A (zh) | 一种共价接枝抗菌多肽的抗菌凝胶及其制备方法 | |
CN113368312B (zh) | 一种可生物降解自粘附水凝胶的制备方法及其应用 | |
CN112999412B (zh) | 用于伤口愈合的水凝胶敷料及其制备方法 | |
CN113999406B (zh) | 一种多功能抗菌水凝胶敷料的制备方法及应用 | |
Liu et al. | Ultra-stretchable, tissue-adhesive, shape-adaptive, self-healing, on-demand removable hydrogel dressings with multiple functions for infected wound healing in regions of high mobility | |
Wang et al. | Bio-inspired hydrogel-based bandage with robust adhesive and antibacterial abilities for skin closure | |
CN111635480A (zh) | 一种抗溶胀水凝胶材料及其制备方法 | |
CN115317658A (zh) | 一种抗菌凝胶及其制备方法和应用 | |
CN116650710A (zh) | 一种贻贝启发的多功能双网络交联水凝胶伤口敷料 | |
Wei et al. | Enzymatic one-pot preparation of carboxylmethyl chitosan-based hydrogel with inherent antioxidant and antibacterial properties for accelerating wound healing | |
Liu et al. | Chitosan/poly (ethylene oxide) nanofiber sponge with dual-responsive drug release and excellent antibacterial property | |
Zhang et al. | Cascade enzymatic preparation of carboxymethyl chitosan-based multifunctional hydrogels for promoting cutaneous wound healing | |
Teng et al. | Shape-recoverable macroporous nanocomposite hydrogels created via ice templating polymerization for noncompressible wound hemorrhage | |
US20230211043A1 (en) | Medical adhesive and preparation method thereof | |
WO2024000860A1 (zh) | 自粘性可吸收生物补片及其制备方法和应用 | |
CN116392629A (zh) | 一种多功能水凝胶敷料及其制备方法和应用 | |
CN115322296B (zh) | 肝素功能化水凝胶及其制备方法与应用 | |
CN115536919A (zh) | 一种改性壳聚糖粘附水凝胶及其制备方法和应用 |
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 |