CN110124089A - 一种可剥离型多孔抗菌生物泡沫敷料及其制备方法 - Google Patents
一种可剥离型多孔抗菌生物泡沫敷料及其制备方法 Download PDFInfo
- Publication number
- CN110124089A CN110124089A CN201910310333.7A CN201910310333A CN110124089A CN 110124089 A CN110124089 A CN 110124089A CN 201910310333 A CN201910310333 A CN 201910310333A CN 110124089 A CN110124089 A CN 110124089A
- Authority
- CN
- China
- Prior art keywords
- foam dressing
- dressing
- preparation
- antibacterial biological
- porous
- 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
- 239000006260 foam Substances 0.000 title claims abstract description 73
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 48
- 238000002360 preparation method Methods 0.000 title claims abstract description 42
- 239000000463 material Substances 0.000 claims abstract description 21
- 239000000839 emulsion Substances 0.000 claims abstract description 15
- 239000000178 monomer Substances 0.000 claims abstract description 14
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims abstract description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 33
- 101100172132 Mus musculus Eif3a gene Proteins 0.000 claims description 24
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 239000000243 solution Substances 0.000 claims description 18
- 239000007864 aqueous solution Substances 0.000 claims description 15
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 claims description 12
- 239000004094 surface-active agent Substances 0.000 claims description 12
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 11
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 11
- 229920000053 polysorbate 80 Polymers 0.000 claims description 11
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 10
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 claims description 10
- 239000002131 composite material Substances 0.000 claims description 10
- 230000004048 modification Effects 0.000 claims description 10
- 238000012986 modification Methods 0.000 claims description 10
- 239000011701 zinc Substances 0.000 claims description 10
- 229910052725 zinc Inorganic materials 0.000 claims description 10
- 239000005751 Copper oxide Substances 0.000 claims description 9
- 229910000431 copper oxide Inorganic materials 0.000 claims description 9
- 239000003431 cross linking reagent Substances 0.000 claims description 9
- 239000003999 initiator Substances 0.000 claims description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 7
- 239000008103 glucose Substances 0.000 claims description 7
- 239000011148 porous material Substances 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 125000004386 diacrylate group Chemical group 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 4
- 238000006116 polymerization reaction Methods 0.000 claims description 3
- 238000013019 agitation Methods 0.000 claims description 2
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 2
- 239000005977 Ethylene Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 238000001035 drying Methods 0.000 claims 1
- 230000001954 sterilising effect Effects 0.000 claims 1
- 238000004659 sterilization and disinfection Methods 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 abstract description 34
- 206010052428 Wound Diseases 0.000 abstract description 33
- 230000029663 wound healing Effects 0.000 abstract description 18
- 230000003993 interaction Effects 0.000 abstract description 4
- 235000015097 nutrients Nutrition 0.000 abstract description 3
- 230000002441 reversible effect Effects 0.000 abstract description 3
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 abstract description 2
- 238000013461 design Methods 0.000 abstract description 2
- 230000012666 negative regulation of transcription by glucose Effects 0.000 abstract description 2
- 230000008614 cellular interaction Effects 0.000 abstract 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 23
- 229920001287 Chondroitin sulfate Polymers 0.000 description 23
- 229940059329 chondroitin sulfate Drugs 0.000 description 23
- 239000012071 phase Substances 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 238000012545 processing Methods 0.000 description 19
- 239000002953 phosphate buffered saline Substances 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 description 12
- 238000001556 precipitation Methods 0.000 description 12
- 235000019441 ethanol Nutrition 0.000 description 11
- 238000000034 method Methods 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 8
- 235000019394 potassium persulphate Nutrition 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 229920000671 polyethylene glycol diacrylate Polymers 0.000 description 7
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 7
- 229920002554 vinyl polymer Polymers 0.000 description 7
- 241000894006 Bacteria Species 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 241000191967 Staphylococcus aureus Species 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 229910021389 graphene Inorganic materials 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000000845 anti-microbial effect Effects 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 5
- 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 5
- 210000003491 skin Anatomy 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 239000000908 ammonium hydroxide Substances 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 239000012154 double-distilled water Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 239000002114 nanocomposite Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000009210 therapy by ultrasound Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- QWMJEUJXWVZSAG-UHFFFAOYSA-N (4-ethenylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=C)C=C1 QWMJEUJXWVZSAG-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 206010020649 Hyperkeratosis Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 206010072170 Skin wound Diseases 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
- 239000004327 boric acid Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000002872 contrast media Substances 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- XKKVXDJVQGBBFQ-UHFFFAOYSA-L zinc ethanol diacetate Chemical compound C(C)O.C(C)(=O)[O-].[Zn+2].C(C)(=O)[O-] XKKVXDJVQGBBFQ-UHFFFAOYSA-L 0.000 description 3
- IPCXNCATNBAPKW-UHFFFAOYSA-N zinc;hydrate Chemical compound O.[Zn] IPCXNCATNBAPKW-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 2
- VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000001332 colony forming effect Effects 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 230000036074 healthy skin Effects 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000002429 large intestine Anatomy 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000004246 zinc acetate Substances 0.000 description 2
- QHFAXRHEKNHTDH-UHFFFAOYSA-N (2-ethenylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1C=C QHFAXRHEKNHTDH-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- 241000221931 Hypomyces rosellus Species 0.000 description 1
- 229920001410 Microfiber Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000237536 Mytilus edulis Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 208000031737 Tissue Adhesions Diseases 0.000 description 1
- 206010048629 Wound secretion Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229960001301 amobarbital Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000035587 bioadhesion Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000005034 decoration Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000001408 fungistatic effect Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- -1 glycidyl ester Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000003658 microfiber Substances 0.000 description 1
- 235000020638 mussel Nutrition 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000008385 outer phase Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000010526 radical polymerization reaction Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010129 solution processing Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/18—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/20—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/26—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/425—Porous materials, e.g. foams or sponges
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
-
- 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
- A61L2300/23—Carbohydrates
- A61L2300/236—Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
-
- 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
- A61L2300/412—Tissue-regenerating or healing or proliferative 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Materials Engineering (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Inorganic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明涉及一种可剥离型多孔抗菌生物泡沫敷料及其制备方法,属生物功能材料制备技术领域;本发明通过基于Zn‑CuO@GO稳定的Pickering高内相乳液模板设计了一种可无创剥离型多孔抗菌生物泡沫敷料,这类多孔抗菌生物泡沫敷料不仅可以有效粘附创口,并且可以明显加速创口愈合,同时通过可逆的多价苯硼酸/顺式‑二醇相互作用粘附创口并在葡萄糖作用下实现无痛剥离;Pickering高内相乳液模板赋予了生物泡沫敷料以多孔结构,借而促进细胞相互作用和营养物交换,并最大程度利用活性苯硼酸官能单体;Zn‑CuO@GO的运用提升了生物泡沫敷料的抗菌效果。
Description
技术领域
本发明涉及一种可剥离型多孔抗菌生物泡沫敷料及其制备方法,属生物功能材料制备技术领域。
背景技术
近年来,受河蚌、壁虎和蜘蛛网等粘附机制启发,科学家们开发了多种仿生粘合性生物敷料,并用于受损组织再生和创口愈合。在临床上,这类生物敷料一般需要通过组织粘附剂将其与不同的组织粘合,使生物敷料与受损部位紧密结合,从而促进组织再生。如将可注射水凝胶在凝胶形成之前注入受损部位以及利用创口中存在的天然分子活性基团如巯基和胺基,通过迈克尔加成共价结合将敷料固定到创口等。但是基于生物粘附的生物敷料也有缺陷,譬如其化学惰性经常会导致与受损组织的脱离,降低其抗菌和愈伤效果。此外,一般共价化学粘合是不可逆的,在去除创口敷料时可能对健康皮肤造成二次损伤而不利于敷料的后期置换和剥离。因此,寻求一种无痛剥离的敷料是一个非常有价值的工作。
发明内容
针对现有技术中存在的一些不足,本发明提供了一种乳液模板法制备可剥离型多孔抗菌生物泡沫敷料及其制备方法,本发明制备的材料具较好的抗炎活性和抑菌效果,同时4-乙烯基苯硼酸的引入增强对创面的粘附性的同时实现了敷料的无痛剥离。
为实现上述目的,本发明采用的技术方案如下:
本发明首先提供一种可剥离型多孔抗菌生物泡沫敷料,所述生物泡沫敷料具有三维多孔结构且石墨烯负载锌掺杂氧化铜(Zn-CuO@GO)复合材料颗粒在材料内均匀分布;所述生物泡沫敷料对创面有粘附性,同时具有葡萄糖响应特性可实现敷料的无痛剥离。
本发明还提供一种可剥离型多孔抗菌生物泡沫敷料的制备方法,具体包括如下步骤:
(1)甲基丙烯酸修饰的硫酸软骨素(CSMA)的合成:
首先,将硫酸软骨素钠盐(CS)溶解在磷酸盐缓冲液中(PBS),然后加入一定量甲基丙烯酸缩水甘油酯,将反应溶液在室温下剧烈搅拌;所得产物用丙酮沉淀提取。为了除去残余的甲基丙烯酸缩水甘油酯,将白色产物重新溶解并用氯仿萃取。最后,收集与浓缩水相,再次用丙酮沉淀,产物经冷冻干燥得到甲基丙烯酸修饰的硫酸软骨素(CSMA),-20℃储存备用。
其中,所述硫酸软骨素钠盐与磷酸盐缓冲液的用量为5-10g:100mL,其中磷酸盐缓冲液的pH为5.2-7.4;
所述硫酸软骨素钠盐与甲基丙烯酸缩水甘油酯用量为1 g:1-2mL;
(2)石墨烯负载锌掺杂氧化铜(Zn-CuO@GO)复合材料的制备:
将一定量乙酸铜和乙酸锌通过搅拌溶解在双蒸水中,然后加入乙醇后得到的乙醇/水溶液。随后加入一定量的氧化石墨烯并在高强度超声微波反应器中超声处理(20 kHz,750W)后,将一定量的氨水(28%)注入反应池中调节反应体系pH,继续进行超声辅助的化学反应(20 kHz,750W)。反应一小时,后经离心、双蒸馏水和乙醇逐次洗涤、真空干燥后即可得到所述多刺纳米复合材料。
其中,所述乙酸铜和乙酸锌的质量比为 0.15:0.055,所述乙醇/水溶液的用量为100 mL,其中乙醇和水的体积比为9:1。
所述氧化石墨烯的用量为0.005 g,氨水用量为0.8 mL,pH约为8。
(3)多孔抗菌生物泡沫敷料的制备:
首先将Zn-CuO@GO分散到含表面活性剂Tween-80的水溶液中,再将单体甲基丙烯酸修饰的硫酸软骨素CSMA、交联剂聚乙二醇双丙烯酸酯(PEGDA)、4-乙烯基苯硼酸4-VPBA和引发剂过硫酸钾(KPS)溶解在上述水溶液中作为水相。在搅拌条件下将一定量的甲苯作为油相缓慢加入水相中制备Pickering HIPE模板,随后将制备好的乳液模板转移到离心管中聚合反应。接着将聚合好的材料从模具中取出,并先后加入到丙酮和过量的水中以除去甲苯。最后,将产物多孔抗菌生物泡沫敷料冷冻干燥备用。
其中,所述Zn-CuO@GO和含有表面活性剂Tween-80的水溶液的用量为7-14 mg:7.0mL;其中水溶液中表面活性剂Tween-80的体积浓度为10%。
所述单体CSMA、交联剂聚乙二醇双丙烯酸酯PEGDA、4-VPBA和引发剂过硫酸钾KPS的质量比为:1.0: (0.7-1.5) : (0.1-0.15) : (0.01-0.02);
所述水相和油相的体积比为1.0:(4.0-5.0) ;
所述聚合反应条件为在60 oC下聚合反应0.5-1.0小时。
本发明的有益效果:
本发明提出了一种采用氧化石墨烯负载锌掺杂氧化铜复合材料(Zn-CuO@GO)作为乳化剂、乙烯基功能化硫酸软骨素和乙烯基苯硼酸单体作为外相试剂构建Pickering高内相乳液模板,再经热引发自由基聚合制备多孔抗菌生物泡沫敷料的新方法。
1.本发明采用的苯硼酸(PBA),其具有的可逆亲和作用来实现细胞动态识
别和诱导粘附。而皮肤创口存在丰富的带有1,2-或1,3-顺式二醇的多糖或者蛋白质,将苯硼酸应用到创口粘附性敷料制备中,可利用它们对顺式二醇的高响应性,实现这种以苯硼酸介导的敷料对创口的粘附并加速创口愈合的目的。
2. 高内相乳液(HIPE),是内相体积比大于74%的一种高浓度乳液体系,以其作为模板是可控制备多孔材料的重要工具。将其用于高度多孔的生物材料,可以获得大面积接触创口的效果,进而提高高活性苯硼酸的结合效率。皮克林高内相乳液(Pickering HIPE )是HIPE模板的一种特殊形式,该乳液体系利用功能纳米颗粒取代表面活性剂来乳化乳液体系,以其为模板制备的多孔材料具有更好的机械强度,同时利用某些纳米颗粒固有的磁、热和光学特性,可在多孔材料中引入更多的功能,进一步拓展多孔材料的应用领域。
3. Zn-CuO@GO作为 Pickering高内相乳液模板乳化剂,可赋予制备的敷料抗菌效果,同时显著增强敷料的机械强度;以硫酸软骨素作为基质材料可以增强敷料的抗炎活性,促进水和营养物质的吸收,加速创口愈合;此外,4-乙烯基苯硼酸(4-VPBA)作为功能单体可以与创口可逆性共价结合,增强对创面的粘附性,同时其葡萄糖响应特性可实现敷料的无痛剥离。
总之,本发明基于Zn-CuO@GO稳定的Pickering HIPE模板设计了一种可无创剥离型多孔抗菌生物泡沫敷料。这类多孔抗菌生物泡沫敷料不仅可以有效粘附创口,并且可以明显加速创口愈合。同时通过可逆的多价苯硼酸/顺式-二醇相互作用粘附创口并在葡萄糖作用下实现无痛剥离。Pickering HIPE模板赋予了生物泡沫敷料以多孔结构,借而促进细胞相互作用和营养物交换,并最大程度利用活性苯硼酸官能单体。
附图说明
图1 实施例1中制备的乙烯基修饰的硫酸软骨素的核磁氢谱图。
图2为本发明制备的敷料#1 (A、D),敷料#2 (B、E)和生物泡沫敷料#3 (C、F)的 扫描电镜图。
图3为制备的敷料#1(a)、敷料#2 (b)和生物泡沫敷料#3 (c)的红外光谱图。
图4为制备的敷料对大肠杆菌和金黄色葡萄球菌处理前后的细菌菌落图。
图5为制备的敷料处理后的小鼠创口愈合进程示意图。
图6为制备的敷料#1(B、b)、敷料#2 (C、c)、生物泡沫敷料#3 (C、c)以及对照组纱布处理 (A、a)应用十天后小鼠创口处皮肤组织切片图。
图7为实施例1中生物泡沫敷料#3可逆性黏附的示意图,图A、B为葡萄糖处理前敷料对创面的粘附性;图C为葡萄糖处理后的图。
具体实施方式
下面结合附图以及具体实施例对本发明作进一步的说明,但本发明的保护范围并不限于此。
本发明中同时制备对比材料,在制备过程中不加硼酸或不加皮克林粒子,对得到的材料和本发明制备的多孔抗菌生物泡沫敷料进行对比分析。
实施例1:缺少皮克林粒子的多孔抗菌生物泡沫敷料(对比材料:敷料#1)的制备
(1)甲基丙烯酸修饰的硫酸软骨素(CSMA)的合成
首先,将硫酸软骨素钠盐(CS, 5 g)溶解在100 mL磷酸盐缓冲盐水中(PBS,pH=7.4),然后加入10 mL甲基丙烯酸缩水甘油酯。然后将反应溶液在室温下剧烈搅拌15天。所得产物用丙酮沉淀提取。为了除去残余的甲基丙烯酸缩水甘油酯,将白色产物重新溶解并用氯仿萃取。最后,收集与浓缩水相,再次用丙酮沉淀,产物经冷冻干燥得到乙烯基修饰的硫酸软骨素(CSMA),-20 ℃储存备用。
(2)石墨烯负载锌掺杂氧化铜(Zn-CuO@GO)复合材料的制备
将0.15 g乙酸铜和0.055 g乙酸锌通过搅拌溶解在10 mL双蒸水中,然后加入90 mL乙醇后得到乙醇/水溶液。随后加入0.005 g氧化石墨烯并在高强度超声微波反应器(20 kHz,750W)中超声处理5 min后,将0.8 mL氨水 (28%)注入反应池中调节反应体系pH约为8,继续进行超声(20 kHz, 750W)辅助的化学反应。反应一小时,后经离心、双蒸馏水和乙醇逐次洗涤、真空干燥后即可得到所述多刺纳米复合材料。
(2)多孔抗菌生物泡沫敷料的制备
首先取7.0 mL含表面活性剂Tween-80的水溶液,单体CSMA(1.4 g)、交联剂PEGDA(1.0g)和引发剂KPS(28 mg)溶解在上述水溶液中。在搅拌下将甲苯(35 mL)缓慢加入水相中制备Pickering HIPE模板,随后将制备好的乳液模板转移到50 mL离心管中,并在60 oC下聚合1.0小时。接着将聚合好的材料从模具中取出,并先后加入到丙酮和过量的水中以除去甲苯。最后,将产物敷料#1冷冻干燥备用。
实施例2:缺少硼酸的多孔抗菌生物泡沫敷料(对比材料:敷料#2)的制备
(1)甲基丙烯酸修饰的硫酸软骨素(CSMA)的合成
首先,将硫酸软骨素钠盐(CS, 7 g)溶解在100 mL磷酸盐缓冲盐水中(PBS,pH=7.4),然后加入10 mL甲基丙烯酸缩水甘油酯。然后将反应溶液在室温下剧烈搅拌15天。所得产物用丙酮沉淀提取。为了除去残余的甲基丙烯酸缩水甘油酯,将白色产物重新溶解并用氯仿萃取。最后,收集与浓缩水相,再次用丙酮沉淀,产物经冷冻干燥得到乙烯基修饰的硫酸软骨素(CSMA),-20 ℃储存备用。
(2)石墨烯负载锌掺杂氧化铜(Zn-CuO@GO)复合材料的制备
将0.15 g乙酸铜和0.055 g乙酸锌通过搅拌溶解在10 mL双蒸水中,然后加入90 mL乙醇后得到乙醇/水溶液。随后加入0.005 g氧化石墨烯并在高强度超声微波反应器(20 kHz,750W)中超声处理5 min后,将0.8 mL氨水 (28%)注入反应池中调节反应体系pH约为8,继续进行超声(20 kHz, 750W)辅助的化学反应。反应一小时,后经离心、双蒸馏水和乙醇逐次洗涤、真空干燥后即可得到所述多刺纳米复合材料。
(3)多孔抗菌生物泡沫敷料的制备
首先将10 mg Zn-CuO@GO分散到7.0 mL含表面活性剂Tween-80的水溶液中。然后,单体CSMA(1.4 g)、交联剂PEGDA(2.1 g)和引发剂KPS(14 mg)溶解在上述Zn-CuO@GO分散的水溶液中。在搅拌下将甲苯(30 mL)缓慢加入水相中制备Pickering HIPE模板,随后将制备好的乳液模板转移到50 mL离心管中,并在60 oC下聚合1.0小时。接着将聚合好的材料从模具中取出,并先后加入到丙酮和过量的水中以除去甲苯。最后,将产物敷料#2冷冻干燥备用。
实施例3:多孔抗菌生物泡沫敷料(生物泡沫敷料#3)的制备
(1)甲基丙烯酸修饰的硫酸软骨素(CSMA)的合成
首先,将硫酸软骨素钠盐(CS, 10 g)溶解在100 mL磷酸盐缓冲盐水中(PBS,pH=7.4),然后加入10 mL甲基丙烯酸缩水甘油酯。然后将反应溶液在室温下剧烈搅拌15天。所得产物用丙酮沉淀提取。为了除去残余的甲基丙烯酸缩水甘油酯,将白色产物重新溶解并用氯仿萃取。最后,收集与浓缩水相,再次用丙酮沉淀,产物经冷冻干燥得到甲基丙烯酸修饰的硫酸软骨素(CSMA),-20 ℃储存备用。
(2)石墨烯负载锌掺杂氧化铜(Zn-CuO@GO)复合材料的制备
将0.15 g乙酸铜和0.055 g乙酸锌通过搅拌溶解在10 mL双蒸水中,然后加入90 mL乙醇后得到乙醇/水溶液。随后加入0.005 g氧化石墨烯并在高强度超声微波反应器(20 kHz,750W)中超声处理5 min后,将0.8 mL氨水 (28%)注入反应池中调节反应体系pH约为8,继续进行超声(20 kHz, 750W)辅助的化学反应。反应一小时,后经离心、双蒸馏水和乙醇逐次洗涤、真空干燥后即可得到所述多刺纳米复合材料。
(3)多孔抗菌生物泡沫敷料的制备
首先将7 mg Zn-CuO@GO分散到7.0 mL含表面活性剂Tween-80的水溶液中。然后,单体CSMA(1.4 g)、交联剂PEGDA(1.4 g)、4-VPBA(200 mg)和引发剂KPS(28 mg)溶解在上述Zn-CuO@GO分散的水溶液中。在搅拌下将甲苯(28 mL)缓慢加入水相中制备Pickering HIPE模板,随后将制备好的乳液模板转移到50 mL离心管中,并在60 oC下聚合1.0小时。接着将聚合好的材料从模具中取出,并先后加入到丙酮和过量的水中以除去甲苯。最后,将产物多孔抗菌生物泡沫敷料#3冷冻干燥备用。
图1中为该实施例步骤(1)中制备的甲基丙烯酸修饰的硫酸软骨素(CSMA)的核磁氢谱图,由图可知,本发明成功将乙烯基引入到硫酸软骨素单体中。
图2为所制备敷料#1、#2、#3的扫描电镜图。图中A、D为敷料#1的结构图及局部放大图,可以看出,缺少了皮克林粒子的存在,所得的多孔生物泡沫虽然基本上保留了其微纤维状结构,但结构较为破碎。图中B、E为敷料#2的结构图及局部放大图,可以看出,该泡沫具有完整的三维多孔结构且Zn-CuO@GO稳定了材料结构。图中C、F为生物泡沫敷料#3的结构图及局部放大图,可以看出,该泡沫具有较好的三维多孔结构且Zn-CuO@GO颗粒在材料内均匀分布。
图3为该本发明所制备敷料#1、#2、#3的红外光谱图,图中c为生物泡沫敷料#3的光谱图,表明4-VPBA成功引入材料中。
实施例4:多孔抗菌生物泡沫敷料(生物泡沫敷料#4)的制备
(1)甲基丙烯酸修饰的硫酸软骨素(CSMA)的合成
首先,将硫酸软骨素钠盐(CS, 5 g)溶解在100 mL磷酸盐缓冲盐水中(PBS,pH=7.4),然后加入10 mL甲基丙烯酸缩水甘油酯。然后将反应溶液在室温下剧烈搅拌15天。所得产物用丙酮沉淀提取。为了除去残余的甲基丙烯酸缩水甘油酯,将白色产物重新溶解并用氯仿萃取。最后,收集与浓缩水相,再次用丙酮沉淀,产物经冷冻干燥得到乙烯基修饰的硫酸软骨素(CSMA),-20 ℃储存备用。
(2)石墨烯负载锌掺杂氧化铜(Zn-CuO@GO)复合材料的制备同实施例3。
(3)多孔抗菌生物泡沫敷料的制备
首先将10 mg Zn-CuO@GO分散到7.0 mL含表面活性剂Tween-80的水溶液中。然后,单体CSMA(1.4 g)、交联剂PEGDA(1.0 g)、4-VPBA(140 mg)和引发剂KPS(14 mg)溶解在上述Zn-CuO@GO分散的水溶液中。在搅拌下将甲苯(30mL)缓慢加入水相中制备Pickering HIPE模板,随后将制备好的乳液模板转移到50 mL离心管中,并在60 oC下聚合0.5小时。接着将聚合好的材料从模具中取出,并先后加入到丙酮和过量的水中以除去甲苯。最后,将产物多孔抗菌生物泡沫#4冷冻干燥备用。
实施例5:多孔抗菌生物泡沫敷料(生物泡沫敷料#5)的制备
(1)甲基丙烯酸修饰的硫酸软骨素(CSMA)的合成
首先,将硫酸软骨素钠盐(CS, 7 g)溶解在100 mL磷酸盐缓冲盐水中(PBS,pH=7.4),然后加入10 mL甲基丙烯酸缩水甘油酯。然后将反应溶液在室温下剧烈搅拌15天。所得产物用丙酮沉淀提取。为了除去残余的甲基丙烯酸缩水甘油酯,将白色产物重新溶解并用氯仿萃取。最后,收集与浓缩水相,再次用丙酮沉淀,产物经冷冻干燥得到乙烯基修饰的硫酸软骨素(CSMA),-20 ℃储存备用。
(2)石墨烯负载锌掺杂氧化铜(Zn-CuO@GO)复合材料的制备同实施例3。
(3)多孔抗菌生物泡沫敷料的制备
首先将14mg Zn-CuO@GO分散到7.0 mL含表面活性剂Tween-80的水溶液中。然后,单体CSMA(1.4 g)、交联剂PEGDA(2.1 g)、4-VPBA(210 mg)和引发剂KPS(28 mg)溶解在上述Zn-CuO@GO分散的水溶液中。在搅拌下将甲苯(35 mL)缓慢加入水相中制备Pickering HIPE模板,随后将制备好的乳液模板转移到50 mL离心管中,并在60 oC下聚合0.8小时。接着将聚合好的材料从模具中取出,并先后加入到丙酮和过量的水中以除去甲苯。最后,将产物多孔抗菌生物泡沫#5冷冻干燥备用。
实施例6:多孔抗菌生物泡沫敷料(敷料#1、#2、#3)的愈伤性能
(1)抗菌性能
将大肠杆菌(ATCC 25922)或金黄色葡萄球菌(ATCC 29213)保持37℃置于营养液中培养(两者均由江苏大学附属医院提供),当菌落形成单位达到108时离心收集,并用pH为6的浓度为0.85%氯化钠溶液洗涤两次。在37℃下将制备的生物泡沫敷料浸入细菌悬浮液中一定时间后,收集悬浮液中的细菌,并在LB-琼脂平板上涂布过夜,然后计数菌落形成单位(CFU)。
结果表明:敷料#1对大肠杆菌和金黄色葡萄球菌无明显抑制活性;敷料#2对大肠杆菌和金黄色葡萄球菌优异的抗菌活性,与其接触后细菌数目明显减少;敷料#3对大肠杆菌和金黄色葡萄球菌有优异的抗菌活性,与其接触后细菌数目明显减少。
图4为所制备敷料#1、#2、#3对大肠杆菌和金黄色葡萄球菌作用前后的菌落图。可以看出,缺少Zn-CuO@GO作为皮克林粒子,仅CSMA组成的敷料#1无明显抗菌性能。敷料#2和生物泡沫敷料#3表现出良好的抗菌性能。
(2)创口愈合性能
所有实验均在江苏大学动物护理和使用委员会的批准下进行,并且使用体重约250 g的雄性Sprague Dawley (SD)大鼠(由江苏大学实验动物中心提供)来评价材料的愈伤作用。首先剃去大鼠的背毛,通过腹膜注射戊巴比妥(30 mg/kg)来麻醉动物。利用手术刀在大鼠背部制造1.5 cm2面积的皮肤创口,切除的创口随后用20 mg待测试的多孔抗菌生物泡沫敷料覆盖;在麻醉恢复期间,将伤口保持暴露,并将小鼠置于加热垫上。随后每天监测小鼠创口愈合情况。在手术后5天、10天和15天分别麻醉处死动物。研究过程中,每天检查大鼠创口并拍照记录,包括创口在内的皮肤样品在4%多聚甲醛溶液中固定后切片用于组织学分析。
结果表明:敷料#1处理后的创口尺寸在同一时间比对照组(纱布处理)有一定下降,在处理10天后,敷料#1处理的伤口表现出一定加速伤口愈合的趋势,在处理15天后,多孔抗菌生物泡沫敷料处理的创口几近闭合。
敷料#2处理后的创口尺寸在同一时间比对照组(纱布处理)进一步下降,在处理10天后,敷料#2处理的伤口表现出较快的伤口愈合,疤痕几乎消失,在处理15天后,多孔抗菌生物泡沫敷料处理的创口同样几乎完全闭合。
生物泡沫敷料#3处理后的创口尺寸在同一时间比对照组(纱布处理)进一步下降。由于抗菌敷料的消炎性质,创口愈合过程的炎症期明显加速。在处理10天后,生物泡沫敷料#3处理的伤口表现出更快的伤口愈合,疤痕几乎完全消失。在处理15天后,多孔抗菌生物泡沫敷料处理的创口几乎完全闭合,这种由多孔抗菌生物泡沫敷料引起的加速伤口愈合效果可以归因于硫酸软骨素良好的生物相容性、材料的多孔结构以及皮克林粒子抗菌性能的综合作用。
图5为小鼠创口愈合过程图。敷料#1表现出一些加速伤口愈合趋势,可以归因于CSMA较好的生物相容性,以及多孔结构有利于促进体液和营养物质的吸收。敷料#2和#3加速了伤口愈合进程。
图6为生物泡沫应用十天后小鼠皮肤组织切片图。敷料#1治疗组(图中 B、b)的创口有炎症细胞的出现,再次表明了仅CSMA组成的敷料#1无明显抗菌性能。
由于使用的生物泡沫具有高度交联的多孔微观结构,可以充分地吸附来自创口的分泌物。然而由于CSMA的分子骨架大、双键含量少,加上材料本身的脆性,敷料#1在交联后会形成断裂,其吸收创口分泌物的能力较差,虽然能加快伤口愈合进程,但本身并不具有抗菌效果。
敷料#2治疗组(图中C、c)的表皮再生几乎完成,而对照组(纱布处理)仅具有无组织的细胞外基质,表皮尚未修复完成(图中A、a)。在泡沫治疗组中,形成的真皮几乎与健康皮肤一样厚,损伤部位被健康上皮组织完整覆盖。然而,缺少了硼酸的存在,即便在葡萄糖溶液处理下,敷料仍旧难以从创口剥离,剥离过程易对创口造成二次伤害。
生物泡沫敷料#3治疗组(图中D、d)的表皮再生几乎完成,而对照组(纱布处理)仅具有无组织的细胞外基质,表皮尚未修复完成(图中A、a)。在泡沫敷料治疗组中,形成的真皮几乎与健康皮肤一样厚,损伤部位被健康上皮组织完整覆盖。另外,生物泡沫敷料#3处理组观察到明显的角质层,这进一步证明了其可以加速创口愈合和组织再生修复。
图7为生物泡沫敷料可逆性黏附的示意图。可以看出,生物泡沫敷料#3可以有效地附着到皮肤创口上,即使在镊子拉拽下也无法分离,证明了敷料优良的粘着性能(图 A、B)。然而,在注入葡萄糖溶液后,生物泡沫敷料逐渐脱离皮层,并且可以轻易地摘除(图C)。
Claims (8)
1.一种可剥离型多孔抗菌生物泡沫敷料,其特征在于,所述生物泡沫敷料具有三维多孔结构且石墨烯负载锌掺杂氧化铜(Zn-CuO@GO)复合材料颗粒在材料内均匀分布。
2.根据权利要求1所述的一种可剥离型多孔抗菌生物泡沫敷料,其特征在于,所述生物泡沫敷料有粘附性,同时具有葡萄糖响应特性可实现敷料的无痛剥离。
3.一种可剥离型多孔抗菌生物泡沫敷料的制备方法,其特征在于,按照如下方法制备:
将石墨烯负载锌掺杂氧化铜(Zn-CuO@GO)复合材料分散到含表面活性剂Tween-80的水溶液中;
将单体甲基丙烯酸修饰的硫酸软骨素CSMA、交联剂聚乙二醇双丙烯酸酯PEGDA、4-乙烯基苯硼酸4-VPBA和引发剂过硫酸钾KPS溶解在上述水溶液中作为水相;
在搅拌条件下将一定量的甲苯作为油相缓慢加入水相中制备Pickering HIPE模板;
将制备好的乳液模板聚合反应;
将聚合好的材料取出,除去甲苯,干燥备用。
4.根据权利要求3所述的一种可剥离型多孔抗菌生物泡沫敷料的制备方法,其特征在于,所述Zn-CuO@GO和含有表面活性剂Tween-80的水溶液的用量为7-14 mg:7.0 mL;其中水溶液中表面活性剂Tween-80的体积浓度为10%。
5.根据权利要求3所述的一种可剥离型多孔抗菌生物泡沫敷料的制备方法,其特征在于,所述单体CSMA、交联剂聚乙二醇双丙烯酸酯PEGDA、4-VPBA和引发剂过硫酸钾KPS的质量比为:1.0: (0.7-1.5) : (0.1-0.15) : (0.01-0.02)。
6.根据权利要求3所述的一种可剥离型多孔抗菌生物泡沫敷料的制备方法,其特征在于,
所述水相和油相的体积比为1.0:(4.0-5.0) 。
7.根据权利要求3所述的一种可剥离型多孔抗菌生物泡沫敷料的制备方法,其特征在于,所述聚合反应条件为在60 oC下聚合反应0.5-1.0小时。
8.权利要求1所述的一种可剥离型多孔抗菌生物泡沫敷料在制备抗菌、杀菌及创口愈合的药物中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910310333.7A CN110124089A (zh) | 2019-04-17 | 2019-04-17 | 一种可剥离型多孔抗菌生物泡沫敷料及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910310333.7A CN110124089A (zh) | 2019-04-17 | 2019-04-17 | 一种可剥离型多孔抗菌生物泡沫敷料及其制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN110124089A true CN110124089A (zh) | 2019-08-16 |
Family
ID=67570415
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910310333.7A Pending CN110124089A (zh) | 2019-04-17 | 2019-04-17 | 一种可剥离型多孔抗菌生物泡沫敷料及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110124089A (zh) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104784698A (zh) * | 2015-03-09 | 2015-07-22 | 江苏大学 | 多级孔聚乳酸药物载体及其制备方法 |
CN105191982A (zh) * | 2015-10-21 | 2015-12-30 | 江苏大学 | 一种多刺锌掺杂氧化铜纳米颗粒及其制备方法 |
WO2017072186A1 (en) * | 2015-10-30 | 2017-05-04 | Knauf Insulation Sprl | Improved binder compositions and uses thereof |
CN107011609A (zh) * | 2016-01-27 | 2017-08-04 | 中国科学院化学研究所 | 一种具有自恢复能力的高强化学-物理双网络水凝胶及其制备方法与应用 |
-
2019
- 2019-04-17 CN CN201910310333.7A patent/CN110124089A/zh active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104784698A (zh) * | 2015-03-09 | 2015-07-22 | 江苏大学 | 多级孔聚乳酸药物载体及其制备方法 |
CN105191982A (zh) * | 2015-10-21 | 2015-12-30 | 江苏大学 | 一种多刺锌掺杂氧化铜纳米颗粒及其制备方法 |
WO2017072186A1 (en) * | 2015-10-30 | 2017-05-04 | Knauf Insulation Sprl | Improved binder compositions and uses thereof |
CN107011609A (zh) * | 2016-01-27 | 2017-08-04 | 中国科学院化学研究所 | 一种具有自恢复能力的高强化学-物理双网络水凝胶及其制备方法与应用 |
Non-Patent Citations (1)
Title |
---|
吴润润: "锌掺杂氧化铜纳米颗粒及其复合材料的制备与其抗菌、愈伤性能和机理研究", 《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Biswas et al. | Recent advancement of biopolymers and their potential biomedical applications | |
Du et al. | Bioinspired hybrid patches with self-adhesive hydrogel and piezoelectric nanogenerator for promoting skin wound healing | |
CN103230617B (zh) | 一种胶原/壳聚糖微纳纤维复合止血膜材料及其制备方法 | |
CN102258801B (zh) | 一种海藻酸钙海绵医用敷料及其制备方法 | |
Tang et al. | Highly absorbent bio-sponge based on carboxymethyl chitosan/poly-γ-glutamic acid/platelet-rich plasma for hemostasis and wound healing | |
CN109568643B (zh) | 一种含小檗碱的抗菌止血微球的制备方法及其应用 | |
Sheokand et al. | Natural polymers used in the dressing materials for wound healing: Past, present and future | |
CN112341640B (zh) | 一种生物基自修复水凝胶及其制备方法和应用 | |
Zheng et al. | A novel pullulan oxidation approach to preparing a shape memory sponge with rapid reaction capability for massive hemorrhage | |
JP2008291258A (ja) | 水溶性エラスチンの架橋剤 | |
CN104857552B (zh) | 一种止血贴及其制备方法 | |
CN102886063A (zh) | 一种纳米微晶纤维素增强胶原复合基质的制备与应用 | |
Chen et al. | Designing biomimetic scaffolds for skin tissue engineering | |
CN111793899B (zh) | 仿生纳米纤维材料及其制备方法与应用 | |
CN110507842B (zh) | 一种细菌纤维素/透明质酸/ε-聚赖氨酸功能型敷料及其制备方法 | |
CN111407921A (zh) | 一种医用水凝胶敷料、其制备方法及应用 | |
Zheng et al. | Highly stable collagen scaffolds crosslinked with an epoxidized natural polysaccharide for wound healing | |
Balusamy et al. | Electrospun nanofibrous materials for wound healing applications | |
CN104922722A (zh) | 可吸收降解淀粉止血材料的制备方法 | |
Jiao et al. | Recent advances in biomimetic hemostatic materials | |
Liu et al. | A tough and mechanically stable adhesive hydrogel for non-invasive wound repair | |
Zhou et al. | Preparation and application of hemostatic hydrogels | |
CN104436283A (zh) | 一种医用胶原膜材料及其制备方法 | |
CN112007210A (zh) | 一种光引发聚乙二醇基水凝胶敷料及其制备方法 | |
CN108452366B (zh) | 一种鳕鱼皮明胶复合止血敷料及其制备方法 |
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 | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190816 |
|
RJ01 | Rejection of invention patent application after publication |