CN111825858A - 一种基于两性离子和角蛋白的复合水凝胶及其制备方法 - Google Patents
一种基于两性离子和角蛋白的复合水凝胶及其制备方法 Download PDFInfo
- Publication number
- CN111825858A CN111825858A CN202010627818.1A CN202010627818A CN111825858A CN 111825858 A CN111825858 A CN 111825858A CN 202010627818 A CN202010627818 A CN 202010627818A CN 111825858 A CN111825858 A CN 111825858A
- Authority
- CN
- China
- Prior art keywords
- keratin
- composite hydrogel
- zwitterionic
- hydrogel
- zwitterion
- 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
- 239000000017 hydrogel Substances 0.000 title claims abstract description 72
- 102000011782 Keratins Human genes 0.000 title claims abstract description 54
- 108010076876 Keratins Proteins 0.000 title claims abstract description 54
- 239000002131 composite material Substances 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 15
- 239000000178 monomer Substances 0.000 claims abstract description 12
- 239000003999 initiator Substances 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 9
- 229920000642 polymer Polymers 0.000 claims description 5
- 230000002829 reductive effect Effects 0.000 claims description 5
- 238000006116 polymerization reaction Methods 0.000 claims description 4
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 2
- 229920006037 cross link polymer Polymers 0.000 claims description 2
- 239000007870 radical polymerization initiator Substances 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 1
- 239000004254 Ammonium phosphate Substances 0.000 claims 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 claims 1
- 235000019289 ammonium phosphates Nutrition 0.000 claims 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 abstract description 8
- 108090000623 proteins and genes Proteins 0.000 abstract description 8
- 238000001179 sorption measurement Methods 0.000 abstract description 7
- 239000000463 material Substances 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 238000010526 radical polymerization reaction Methods 0.000 abstract description 3
- 206010060932 Postoperative adhesion Diseases 0.000 abstract description 2
- 238000010189 synthetic method Methods 0.000 abstract 1
- 206010052428 Wound Diseases 0.000 description 22
- 208000027418 Wounds and injury Diseases 0.000 description 22
- 239000000243 solution Substances 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 108010006205 fluorescein isothiocyanate bovine serum albumin Proteins 0.000 description 8
- 239000000499 gel Substances 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 6
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 229940098773 bovine serum albumin Drugs 0.000 description 5
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000029663 wound healing Effects 0.000 description 4
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 3
- 229920000742 Cotton Polymers 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000021164 cell adhesion Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 229960003180 glutathione Drugs 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 108010083708 leucyl-aspartyl-valine Proteins 0.000 description 3
- 239000008176 lyophilized powder Substances 0.000 description 3
- PSBDWGZCVUAZQS-UHFFFAOYSA-N (dimethylsulfonio)acetate Chemical compound C[S+](C)CC([O-])=O PSBDWGZCVUAZQS-UHFFFAOYSA-N 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 2
- 239000004971 Cross linker Substances 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- QCSFMCFHVGTLFF-NHCYSSNCSA-N Leu-Asp-Val Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O QCSFMCFHVGTLFF-NHCYSSNCSA-N 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000002861 polymer material Substances 0.000 description 2
- 229920002635 polyurethane Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229920002379 silicone rubber Polymers 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 229940117986 sulfobetaine Drugs 0.000 description 2
- OSSNTDFYBPYIEC-UHFFFAOYSA-N 1-ethenylimidazole Chemical compound C=CN1C=CN=C1 OSSNTDFYBPYIEC-UHFFFAOYSA-N 0.000 description 1
- NULDEVQACXJZLL-UHFFFAOYSA-N 2-(2-aminoethyldisulfanyl)ethylazanium;chloride Chemical compound Cl.NCCSSCCN NULDEVQACXJZLL-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- UQBOJOOOTLPNST-UHFFFAOYSA-N Dehydroalanine Chemical class NC(=C)C(O)=O UQBOJOOOTLPNST-UHFFFAOYSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000003373 anti-fouling effect Effects 0.000 description 1
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 1
- QLULGSLAHXLKSR-UHFFFAOYSA-N azane;phosphane Chemical compound N.P QLULGSLAHXLKSR-UHFFFAOYSA-N 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- NGDIAZZSCVVCEW-UHFFFAOYSA-M sodium;butyl sulfate Chemical compound [Na+].CCCCOS([O-])(=O)=O NGDIAZZSCVVCEW-UHFFFAOYSA-M 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
-
- 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0028—Polypeptides; Proteins; Degradation products thereof
- A61L26/0047—Specific proteins or polypeptides not covered by groups A61L26/0033 - A61L26/0042
-
- 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0066—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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/008—Hydrogels or hydrocolloids
-
- 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/009—Materials resorbable by the body
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/38—Esters containing sulfur
- C08F220/385—Esters containing sulfur and containing nitrogen
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
-
- 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
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2333/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers
- C08J2333/04—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters
- C08J2333/14—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2489/00—Characterised by the use of proteins; Derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明公开了一种基于两性离子和角蛋白的复合水凝胶及其制备方法,该复合水凝胶包括如下原料组分制成:两性离子单体400~600份,角蛋白0~60份,交联剂6~30份和引发剂0~10份,并提供该复合水凝胶的制备方法。本发明的基于两性离子和角蛋白的复合水凝胶具有优异的生物相容性和防粘连效果;合成方法简单,具有优异的可降解性;采用具有良好生物相容性的角蛋白和抗蛋白吸附能力的两性离子化合物单体为原料,通过自由基聚合反应制备了两性离子可降解水凝胶并作为防粘连材料预防术后粘连的发生;可作为防粘连伤口敷料用于生物医学领域。
Description
技术领域
本发明涉及一种复合水凝胶及其制备方法,尤其涉及一种基于两性离子和角蛋白的复合水凝胶及其制备方法。
背景技术
皮肤组织作为抵御外部环境脱水、化学/放射损伤和微生物入侵的第一道屏障,是人体最大的器官。当皮肤受伤时,为了伤口尽快闭合并减少结痂,通常采用敷料覆盖伤口,以防止伤口被细菌感染和大量组织液流失。棉纱布作为伤口敷料,由于其易于使用,治疗成本低以及患者接受度高,至今仍被广泛使用。然而,棉纱布敷料易与受损组织之间发生粘连。在换药期间,纱布与创面分离困难,会对伤口造成二次损伤并延长伤口愈合,尤其是在治疗慢性伤口时。此外,现阶段常用的伤口敷料主要是由聚氨酯、硅橡胶、聚乙烯醇等高分子材料制备而成。新生组织会生长到敷料的微孔中,并附着粘连在里面。伤口愈合后,会导致敷料难以和新生组织表面分离。因此,要求敷料在使用时不粘连创面,揭除时无残留,不损伤创面,不增加病人疼痛等。因此,迫切需要一种具有防伤口粘连敷料,以减轻患者在频繁更换敷料期间所遭受的痛苦以及能够加速伤口的愈合。
两性离子根据其阴离子类型可分为羧铵型(CB),磺铵型(SB)和磷铵型(PB)。两性离子聚合物的同一单体侧链上同时含有阴离子基团和阳离子基团,但是总体呈电中性。两性离子聚合物具有强亲水性和超低生物粘污的特性,可用于生物医学水凝胶的制备。两性离子水凝胶作为一种高水化、柔软的材料,因其独特的防污性能和力学性能,被认为是一种很有前景的创面敷料材料。Wu等制备了具有不同力学性能的聚(磺基甜菜碱甲基丙烯酸酯)(polySBMA)水凝胶,并将其作为创面敷料用于治疗小鼠全层真皮创面。结果表明,较软的polySBMA水凝胶可通过内在的弹性冲动有效地加速伤口愈合,从而改善新血管形成。
然而,两性离子水凝胶较差的细胞相容性和不可降解性限制了其在组织工程和药物载体方面的进一步发展和应用。棉纱布敷料易与受损组织之间发生粘连。在换药期间,纱布与创面分离困难,会对伤口造成二次损伤并延长伤口愈合,尤其是在治疗慢性伤口时。此外,现阶段常用的伤口敷料主要是由聚氨酯、硅橡胶、聚乙烯醇等高分子材料制备而成。新生组织会生长到敷料的微孔中,并附着粘连在里面。伤口愈合后,会导致敷料难以和新生组织表面分离。两性离子水凝胶较差的细胞相容性和不可降解性限制了其在组织工程和药物载体方面的进一步发展和应用。
发明内容
发明目的:本发明的第一目的为提供一种具有优异的生物相容性、防粘连、可降解的基于两性离子和角蛋白的复合水凝胶,本发明的第二目的为提供该复合水凝胶的制备方法。
技术方案:本发明的基于两性离子和角蛋白的复合水凝胶,包括如下原料组分制成:单体400~600份,角蛋白0~60份,交联剂6~30份和引发剂0~10份。
进一步地,两性离子单体制得的聚合物为二硫键交联聚合物。交联剂为还原性敏感交联剂。引发剂为自由基聚合引发剂。角蛋白为还原角蛋白。两性离子为甲基丙烯酸型磺铵型两性离子、羧铵型两性离子或磷铵型两性离子中的一种。
两性离子的结构式为以下中的一种:
本发明的基于两性离子和角蛋白的复合水凝胶的制备方法,包括如下步骤:
将两性离子单体、交联剂和角蛋白形成预聚液,加入引发剂,在40~65℃下反应,然后置于有氧环境下使角蛋白上的巯基自交联以形成二硫键,制得基于两性离子和角蛋白的复合水凝胶。
优选的,角蛋白从人类或动物的毛发中,经还原法提取得到。
本发明使用了一种可降解的交联剂制备水凝胶并复合细胞相容性良好的角蛋白。具体来说是将二硫键引入到水凝胶中,使水凝胶赋予还原性敏感,在还原性环境下促使二硫键断裂发生降解而释放药物。在还原剂如谷胱甘肽(GSH)、半胱氨酸(Cys)和二硫苏糖醇(DTT)的存在下,二硫键很容易断裂。角蛋白生物材料是优异的无抗原材料,具有良好的细胞相容性、生物降解性和非免疫原性。角蛋白中的RGD和LDV氨基酸片段有助于细胞粘附,生长和迁移。角蛋白基药物载体具有二硫键和羧基基团,具有双重GSH/pH响应。
有益效果:与现有技术相比,本发明具有如下显著优点:本发明的基于两性离子和角蛋白的复合水凝胶具有优异的生物相容性和防粘连效果;本发明制备的水凝胶合成方法简单,具有优异的可降解性;采用具有良好生物相容性的角蛋白和抗蛋白吸附能力的两性离子化合物单体为原料,通过自由基聚合反应制备了两性离子可降解水凝胶并作为防粘连材料预防术后粘连的发生;可作为防粘连伤口敷料用于生物医学领域。
附图说明
图1(a)-(c)为本发明复合水凝胶吸附FITC-BSA荧光图,图1(a)为PDMAPS水凝胶吸附FITC-BSA荧光图,图1(b)为PDMAPS/Keratin水凝胶吸附FITC-BSA荧光图,图1(c)为TCPS吸附FITC-BSA荧光图;
图2为本发明复合水凝胶MTT直接法结果图;
图3为本发明复合水凝胶自修复为凝胶状态图;
图4为本发明复合水凝胶吸水后不流动图;
图5(a)-(b)为本发明复合水凝胶呈现凝胶状图。
具体实施方式
下面结合实施例对本发明的技术方案作进一步说明。
实施例1
1.交联剂BACy的合成
交联剂BACy是通过将胱胺二盐酸盐的两个氨基丙烯酸化合成,合成路线如下:
将盐酸胱胺(5.8g,0.025mol)添加到配有温度计和两个10mL恒压滴液漏斗的100mL三口烧瓶中,加入25mL去离子水。将混合物冰水冷却后,在搅拌下同时缓慢滴加丙烯酰氯(4.65g,0.05mol)的二氯甲烷(10mL)溶液和NaOH溶液(4.0g,0.1mol;10mL),控制滴加时间在0.5h以上,滴加过程中温度始终保持在0-5℃。滴加完毕后,将反应混合物在室温下搅拌2h以上。分离有机相,并用二氯甲烷(5×50mL)少量多次萃取有机相。收集的有机相用无水Na2SO4干燥,过滤后,用旋转蒸发法去除溶剂二氯甲烷,得到白色粉末固体。最后用乙酸乙酯/正庚烷混合物(体积比:1:2)重结晶。产率:4.12g(61.5%)。
2.两性离子聚合物水凝胶(以PDMAPS为例)的制备
采用自由基聚合制备二硫键交联的PDMAPS(DMAPS-SS-DMAPS)水凝胶。准确称取一定比例的单体DMAPS、交联剂BACy、引发剂APS。将单体DMAPS、交联剂BACy加入一干净螺口瓶中,用2mL除氧去离子水溶解,随后加入引发剂APS形成水凝胶预聚液,在65℃的恒温烘箱下反应24h。取出凝胶,用蒸馏水浸泡72h,每12h换一次水,除去未反应的反应物。
3PDMAPS/Keratin水凝胶的制备
在制备PDMAPS水凝胶的基础上,将还原角蛋白掺入混合溶液中以形成水凝胶,然后置于有氧环境下或者辅助添加双氧水等氧化剂以使角蛋白上的巯基自交联以形成二硫键,不同交联剂、角蛋白含量的水凝胶配方如表1所示。
表1不同交联剂、角蛋白含量水凝胶配方
实施例2
抗蛋白质吸附性能测试:
异硫氰酸荧光素(FITC)标记牛血清白蛋白(BSA)通过FITC与BSA缀合制备FITC-BSA。首先以100mM NaHCO3(pH=9)为溶剂配制10mg/mL的BSA溶液,将FITC溶于DMSO中配制成1mg/mL的溶液备用。在避光添加下将FITC缓慢滴加于BSA中,并反应2h。结束后,用100mMNaHCO3(pH=9)避光透析直至透析液呈无色,再用去离子水透析三次,得到FITC-BSA溶液备用。
将交联度为5%的薄片状PDMAPS和PDMAPS/Keratin水凝胶置于6孔细胞培养板中,向样品孔加入等量FITC-BSA溶液,使凝胶完全浸没。在4℃下避光孵化12h,弃去FITC-BSA溶液,用PBS缓冲液(pH=7.4)冲洗三次,在荧光显微镜下观察蛋白吸附情况。
由图1(a)-(c)可以看出,空白细胞培养板上粘附了大量的蛋白,而PDMAPS水凝胶和PDMAPS/Keratin基本无蛋白吸附,这体现了两性离子优良的抗蛋白吸附性能。
实施例3
水凝胶与L929细胞相互作用:
在细胞培养前,将制备的水凝胶在指定的培养基中进行5d的培养基解毒过程。在此过程中,未反应的交联剂被有效地从水凝胶中去除,水凝胶中必需的营养物质得到了富集。为了研究水凝胶与细胞的相互作用,将圆形水凝胶在超净台中紫外照射杀菌后置于24孔细胞培养板中。用胰蛋白酶消化L-929细胞,配成3×104cells/mL的细胞悬液。向每孔加入1mL细胞悬液,37℃、5%CO2的培养箱中培养3d。结束后,每孔加入浓度为0.5mg/mL的100μL MTT溶液,培养箱中继续培养4h,吸弃MTT溶液和细胞培养液,PBS溶液洗涤后加入500μLDMSO,避光震荡30min,吸取溶液转入96孔板中,使用酶标仪测量490nm处OD值。
两性离子水凝胶具有极低的蛋白质吸附和细胞粘附性、可操作性和出色的机械性能。Carr L等制备磺基甜菜碱乙烯基咪唑水凝胶,发现其细胞粘附力较低。课题组前期工作已证明角蛋白材料具有良好的细胞相容性,并且可以促进细胞增殖和分化。通过MTT评估L-929细胞在水凝胶上的粘附及生长活力。图2为直接法的实验结果,在PDMAPS/角蛋白水凝胶和PDMAPS水凝胶对比之间观察到L-929细胞活性具有统计学显著差异。PDMAPS/角蛋白的细胞活力随角蛋白含量的增加而增强,表明角蛋白具有出色的细胞相容性。细胞外基质(ECM)与整合素相互作用,支持细胞附着、增殖和迁移,而角蛋白具有与ECM相似的RGD(Arg-Gly-Asp)和LDV(Leu-Asp-Val)等氨基酸序列。
实施例4
PDMAPS/Keratin水凝胶冻干粉及其可注射性研究:
当两性离子微凝胶发生重建时,微凝胶内部的共价交联以及微凝胶粒子间的超分子作用联合形成具有支撑模量和可调粘弹性的两性离子可注射颗粒(zwitterionicinjectablepellet,ZIP)。ZIP可以冻干成无菌粉末,在重新水化后可以恢复其强度和弹性,从而简化了存储和配制过程。该冻干粉可与任何细胞或药物的水溶性悬浮液进行混合,并迅速复合成型,这种材料在许多应用领域显示出巨大的潜力,有望应用于可注射细胞培养支架和水凝胶型伤口敷料。因此,将溶胀后的水凝胶冷冻干燥后,磨成粉末备用。其可注射性和可自愈行为通过针头注射和迅速恢复到一个倒置的小瓶或在一个平面上的自修复为凝胶状态体现,如图3所示。
图4为制备的两性离子冻干粉,加入蒸馏水后倒置螺口瓶,冻干粉吸水后成凝胶状,且不流动,具有一定的强度。在图5(a)-(b)中,冻干粉通过针头注射成型,具备一定的可注射,在冻干粉中加入蒸馏水,冻干粉呈现凝胶状。该水凝胶冻干粉有望应用于伤口敷料,在创口处洒上水凝胶冻干粉。冻干粉吸收渗出的组织液后形成凝胶,由于两性离子的抗粘连特性,水凝胶敷料可轻易去除,减轻病者的疼痛。
Claims (9)
1.一种基于两性离子和角蛋白的复合水凝胶,其特征在于,包括如下原料组分制成:两性离子单体400~600份,角蛋白0~60份,交联剂6~30份和引发剂0~10份。
2.根据权利要求1所述基于两性离子和角蛋白的复合水凝胶,其特征在于:所述两性离子单体制得的聚合物为二硫键交联聚合物。
3.根据权利要求1所述基于两性离子和角蛋白的复合水凝胶,其特征在于:所述交联剂为还原性敏感交联剂。
4.根据权利要求1所述基于两性离子和角蛋白的复合水凝胶,其特征在于:所述引发剂为自由基聚合引发剂。
5.根据权利要求1所述基于两性离子和角蛋白的复合水凝胶,其特征在于:所述角蛋白为还原角蛋白。
6.根据权利要求1所述基于两性离子和角蛋白的复合水凝胶,其特征在于:所述两性离子为甲基丙烯酸型磺铵型两性离子、羧铵型两性离子或磷铵型两性离子中的一种。
8.一种权利要求1所述基于两性离子和角蛋白的复合水凝胶的制备方法,其特征在于,包括如下步骤:
将两性离子单体、交联剂和角蛋白形成预聚液,加入引发剂,在40~65℃下反应,然后置于有氧环境下使角蛋白上的巯基自交联以形成二硫键,制得基于两性离子和角蛋白的复合水凝胶。
9.根据权利要求8所述基于两性离子和角蛋白的复合水凝胶的制备方法,其特征在于:所述角蛋白从人类或动物的毛发中,经还原法提取得到。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010627818.1A CN111825858B (zh) | 2020-07-02 | 2020-07-02 | 一种基于两性离子和角蛋白的复合水凝胶及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010627818.1A CN111825858B (zh) | 2020-07-02 | 2020-07-02 | 一种基于两性离子和角蛋白的复合水凝胶及其制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111825858A true CN111825858A (zh) | 2020-10-27 |
CN111825858B CN111825858B (zh) | 2023-04-25 |
Family
ID=72899612
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010627818.1A Active CN111825858B (zh) | 2020-07-02 | 2020-07-02 | 一种基于两性离子和角蛋白的复合水凝胶及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111825858B (zh) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105664238A (zh) * | 2016-02-25 | 2016-06-15 | 天津大学 | 一种两性离子水凝胶敷料的制备方法和应用 |
CN106867000A (zh) * | 2017-03-16 | 2017-06-20 | 苏州佰锐生物科技有限公司 | 一种促进角蛋白溶解及增强角蛋白材料强度的方法 |
US20180251505A1 (en) * | 2016-11-17 | 2018-09-06 | University Of South Carolina | Keratin-based hydrogels |
CN108601723A (zh) * | 2015-11-03 | 2018-09-28 | 硕腾服务有限责任公司 | 溶胶-凝胶聚合物复合材料及其用途 |
CN110372885A (zh) * | 2019-06-28 | 2019-10-25 | 浙江工业大学 | 一种壳聚糖/两性离子与丙烯酸共聚物双网络自愈合水凝胶及其制备方法 |
CN110384831A (zh) * | 2019-06-30 | 2019-10-29 | 天津大学 | 用于术后防粘连的两性离子水凝胶及交联剂、聚合物的制备方法 |
CN110483705A (zh) * | 2019-08-14 | 2019-11-22 | 西安工业大学 | 一种基于角蛋白的止血水凝胶及其制备方法 |
-
2020
- 2020-07-02 CN CN202010627818.1A patent/CN111825858B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108601723A (zh) * | 2015-11-03 | 2018-09-28 | 硕腾服务有限责任公司 | 溶胶-凝胶聚合物复合材料及其用途 |
CN105664238A (zh) * | 2016-02-25 | 2016-06-15 | 天津大学 | 一种两性离子水凝胶敷料的制备方法和应用 |
US20180251505A1 (en) * | 2016-11-17 | 2018-09-06 | University Of South Carolina | Keratin-based hydrogels |
CN106867000A (zh) * | 2017-03-16 | 2017-06-20 | 苏州佰锐生物科技有限公司 | 一种促进角蛋白溶解及增强角蛋白材料强度的方法 |
CN110372885A (zh) * | 2019-06-28 | 2019-10-25 | 浙江工业大学 | 一种壳聚糖/两性离子与丙烯酸共聚物双网络自愈合水凝胶及其制备方法 |
CN110384831A (zh) * | 2019-06-30 | 2019-10-29 | 天津大学 | 用于术后防粘连的两性离子水凝胶及交联剂、聚合物的制备方法 |
CN110483705A (zh) * | 2019-08-14 | 2019-11-22 | 西安工业大学 | 一种基于角蛋白的止血水凝胶及其制备方法 |
Non-Patent Citations (2)
Title |
---|
YUXUE GAO ET AL.: "Preparation and properties of a highly elastic galactomannan- poly(acrylamide- N, N-bis (acryloyl) cysteamine) hydrogel with reductive stimuli-responsive degradable properties", 《CARBOHYDRATE POLYMERS》 * |
孙晓霞等: "角蛋白生物材料在创伤愈合中的应用研究进展", 《材料导报》 * |
Also Published As
Publication number | Publication date |
---|---|
CN111825858B (zh) | 2023-04-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Cho et al. | Recent progress in self-healing polymers and hydrogels based on reversible dynamic B–O bonds: boronic/boronate esters, borax, and benzoxaborole | |
CN110240712B (zh) | 一种组织粘合用的高拉伸、高粘性、自愈合双网络水凝胶及其制备方法和应用 | |
EP3191016B1 (en) | Functionalized zwitterionic and mixed charge polymers, related hydrogels, and methods for their use | |
US20170014543A1 (en) | HYDROGEL BASED ON γ-POLYGLUTAMIC ACID AND ε-POLYLYSINE CROSSLINKED POLYMER, AND PREPARATION METHOD THEREFOR | |
JP5376543B2 (ja) | ポリイオンデンドリマー、及びそれよりなるハイドロゲル | |
Sapru et al. | Non-immunogenic, porous and antibacterial chitosan and Antheraea mylitta silk sericin hydrogels as potential dermal substitute | |
Huang et al. | A tannin-functionalized soy protein-based adhesive hydrogel as a wound dressing | |
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 | |
SE541313C2 (en) | Amphiphilic antimicrobial hydrogel | |
CN115975224B (zh) | 一种pH/ROS双响应的组织粘附载药水凝胶及其制备方法和应用 | |
CN108484936A (zh) | 一种接枝改性材料所制备的水凝胶及其制备方法和应用 | |
CN114561046A (zh) | 一种胍基透明质酸型抗菌水凝胶及其制备方法和应用 | |
CN106084140B (zh) | 一种含胍基基团的聚酰胺、其制备方法以及由其制得的水凝胶 | |
Balcioglu et al. | Photocrosslinkable gelatin/collagen based bioinspired polyurethane-acrylate bone adhesives with biocompatibility and biodegradability | |
CN111450307B (zh) | 一种双组份医用粘合剂的制备方法 | |
CN111825858A (zh) | 一种基于两性离子和角蛋白的复合水凝胶及其制备方法 | |
Xu et al. | Dually crosslinked self-healing hydrogels originating from cell-enhanced effect | |
KR20100009305A (ko) | 키토산 스폰지의 제조방법 및 이를 이용한 창상도포재 | |
CN115337446B (zh) | 一种促进伤口愈合的生物基粘附性水凝胶贴片的制备方法及其产品和应用 | |
Liu et al. | Biocompatible dual network bovine serum albumin-loaded hydrogel-accelerates wound healing | |
JPH09278803A (ja) | 医療用手当材 | |
Wang et al. | Double Cross-Linked Hydrogel Dressings Based on Triblock Copolymers Bearing Antifreezing, Antidrying, and Inherent Antibacterial Properties | |
CN110755677B (zh) | 一种聚氨基酸水凝胶敷料及其制备方法与应用 | |
CN110841103B (zh) | 一种桑叶粉-桑蚕丝胶/柞蚕丝素共混膜及其制备方法 | |
CN115197442B (zh) | 治疗胃穿孔的可注射自愈合水凝胶敷料、制备方法及用途 |
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 |