CN116650709A - Polyvinyl alcohol-based composite hydrogel, and preparation method and application thereof - Google Patents
Polyvinyl alcohol-based composite hydrogel, and preparation method and application thereof Download PDFInfo
- Publication number
- CN116650709A CN116650709A CN202310561425.9A CN202310561425A CN116650709A CN 116650709 A CN116650709 A CN 116650709A CN 202310561425 A CN202310561425 A CN 202310561425A CN 116650709 A CN116650709 A CN 116650709A
- Authority
- CN
- China
- Prior art keywords
- pva
- polyvinyl alcohol
- hydrogel
- shk
- solution
- 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
- 239000004372 Polyvinyl alcohol Substances 0.000 title claims abstract description 200
- 229920002451 polyvinyl alcohol Polymers 0.000 title claims abstract description 200
- 239000000017 hydrogel Substances 0.000 title claims abstract description 135
- 239000002131 composite material Substances 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- NEZONWMXZKDMKF-JTQLQIEISA-N Alkannin Chemical compound C1=CC(O)=C2C(=O)C([C@@H](O)CC=C(C)C)=CC(=O)C2=C1O NEZONWMXZKDMKF-JTQLQIEISA-N 0.000 claims abstract description 116
- 241001071917 Lithospermum Species 0.000 claims abstract description 116
- UNNKKUDWEASWDN-UHFFFAOYSA-N alkannin Natural products CC(=CCC(O)c1cc(O)c2C(=O)C=CC(=O)c2c1O)C UNNKKUDWEASWDN-UHFFFAOYSA-N 0.000 claims abstract description 116
- 238000004132 cross linking Methods 0.000 claims abstract description 30
- 239000000243 solution Substances 0.000 claims description 51
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 239000012670 alkaline solution Substances 0.000 claims description 20
- 238000005406 washing Methods 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- 238000006136 alcoholysis reaction Methods 0.000 claims description 11
- 238000006116 polymerization reaction Methods 0.000 claims description 11
- 230000007935 neutral effect Effects 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 8
- 238000004140 cleaning Methods 0.000 claims description 5
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000012459 cleaning agent Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 21
- 206010052428 Wound Diseases 0.000 abstract description 19
- 208000027418 Wounds and injury Diseases 0.000 abstract description 19
- 230000000694 effects Effects 0.000 abstract description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 9
- 239000001257 hydrogen Substances 0.000 abstract description 9
- 230000001737 promoting effect Effects 0.000 abstract description 7
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 6
- 239000003963 antioxidant agent Substances 0.000 abstract description 5
- 230000003078 antioxidant effect Effects 0.000 abstract description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 abstract description 5
- 230000004071 biological effect Effects 0.000 abstract description 3
- 230000035876 healing Effects 0.000 abstract description 2
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 20
- 229940079593 drug Drugs 0.000 description 17
- 230000000052 comparative effect Effects 0.000 description 16
- 241000700159 Rattus Species 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 230000029663 wound healing Effects 0.000 description 14
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 10
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 10
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 10
- 229960001285 quercetin Drugs 0.000 description 10
- 235000005875 quercetin Nutrition 0.000 description 10
- 239000011259 mixed solution Substances 0.000 description 9
- 239000008367 deionised water Substances 0.000 description 8
- 229910021641 deionized water Inorganic materials 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000011068 loading method Methods 0.000 description 7
- 230000000844 anti-bacterial effect Effects 0.000 description 5
- 230000021164 cell adhesion Effects 0.000 description 5
- 235000013824 polyphenols Nutrition 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 229940124350 antibacterial drug Drugs 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 238000002791 soaking Methods 0.000 description 4
- 230000007547 defect Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 241000411851 herbal medicine Species 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 208000037816 tissue injury Diseases 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 230000037314 wound repair Effects 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 description 1
- 229930192627 Naphthoquinone Natural products 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 108010087230 Sincalide Proteins 0.000 description 1
- 241000863480 Vinca Species 0.000 description 1
- 206010053692 Wound complication Diseases 0.000 description 1
- 206010048038 Wound infection Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229940116978 human epidermal growth factor Drugs 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- -1 naphthoquinone compound Chemical class 0.000 description 1
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 230000003651 pro-proliferative effect Effects 0.000 description 1
- 230000002633 protecting effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
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
- 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
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0014—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form 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
- 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
- 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
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/408—Virucides, spermicides
-
- 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
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a polyvinyl alcohol-based composite hydrogel, a preparation method and application thereof. The composite hydrogel is obtained by crosslinking Shikonin (SHK) and polyvinyl alcohol (PVA). According to the invention, SHK and PVA are crosslinked in an alkaline environment, wherein a hydroxyl group on a PVA side chain and a phenolic hydroxyl group in SHK molecules can form a stable and firm hydrogen bond under the alkaline condition, so that SHK is anchored on the PVA molecular chain on the surface of the hydrogel. When the SHK/PVA hydrogel encounters moist environments such as cells and tissues, the SHK/PVA hydrogel swells, hydrogen bonds are opened, SHK existing on the surface of the hydrogel is released into the surrounding environment in the form of molecules of the original medicine, the biological activity effects such as anti-inflammatory, antioxidant and repairing are exerted, and the aim of promoting the rapid healing of wounds can be effectively achieved.
Description
Technical Field
The invention relates to the technical field of hydrogel preparation, in particular to a polyvinyl alcohol-based composite hydrogel, a preparation method and application thereof.
Background
The skin is used as the first defense line of human body and has important functions of protecting, regulating, secreting and the like. However, skin trauma due to burns, trauma, infection and chronic diseases remains a significant challenge worldwide. Delayed wound healing increases the risk of wound infection or complications and incurs high treatment costs, and therefore there is an urgent need to develop a rapid and effective wound repair material (i.e., wound dressing).
In order to achieve rapid wound healing, wound dressings are required to have a variety of functions such as anti-inflammatory, antibacterial, angiogenic, pro-proliferative and remodelling. However, conventional wound dressings are dry and do not provide a moist environment for wound healing. Hydrogels can retain a significant amount of moisture, creating a moist healing environment, and are considered ideal wound repair dressings. Among them, polyvinyl alcohol (PVA) hydrogel is a non-toxic, non-immunogenic polymer, which is widely used in the field of tissue engineering due to its stable chemical properties, high water content, good permeability and biocompatibility. However, PVA hydrogels alone do not possess bioactivity and antimicrobial properties and do not promote cell adhesion and wound healing.
In order to make the wound dressing prepared at present have antibacterial performance and promote cell adhesion and wound healing, antibacterial drugs (such as ciprofloxacin) and growth factors (such as recombinant human epidermal growth factor (rhEGF)) are mostly introduced into the hydrogel dressing, which can obviously increase the preparation cost of the dressing, the preparation process of the dressing is complicated, the active ingredients of the growth factors have severe requirements on the storage and transportation of the drug-loaded dressing, the transportation cost is greatly increased, and the biocompatibility of the wound dressing can be deteriorated due to the addition of the antibacterial drugs.
Disclosure of Invention
In view of the above, the present invention aims to provide a polyvinyl alcohol-based composite hydrogel, a preparation method and applications thereof. The polyvinyl alcohol-based composite hydrogel has low preparation cost, excellent bioactivity and biocompatibility, and can promote cell adhesion and wound healing.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the invention provides a polyvinyl alcohol-based composite hydrogel, which is obtained by crosslinking shikonin and polyvinyl alcohol.
Preferably, the mass ratio of the shikonin to the polyvinyl alcohol is (0-3): 97-100.
Preferably, the polymerization degree of the polyvinyl alcohol is 1000 to 3000.
Preferably, the alcoholysis degree of the polyvinyl alcohol is 98-100%.
In a second aspect, the present invention also provides a method for preparing the polyvinyl alcohol-based composite hydrogel, which comprises the following steps:
s1: drying the polyvinyl alcohol solution to obtain polyvinyl alcohol hydrogel;
s2: crosslinking shikonin and the polyvinyl alcohol hydrogel in an alkaline environment to obtain the polyvinyl alcohol-based composite hydrogel.
5. The method according to claim 4, wherein the drying treatment is carried out at a temperature of 20 to 80 ℃.
Preferably, the alkaline environment is provided by an alkaline solution.
Preferably, the alkaline solution is selected from any one or more of sodium hydroxide solution, potassium hydroxide solution, ammonia water or sodium ethoxide solution.
Preferably, the concentration of OH-in the alkaline solution is 0-6 mol/L.
Preferably, the time of the crosslinking is 10 to 60 minutes.
Preferably, the cross-linking is completed and further comprises a washing step.
Preferably, the cleaning agent is water.
Preferably, the washing is ended until the washing liquid is neutral.
In a third aspect, the present invention provides a wound dressing comprising the polyvinyl alcohol-based composite hydrogel according to the above technical solution.
Compared with the prior art, the invention has the beneficial effects that:
according to the invention, a natural Chinese herbal medicine component Shikonin (SHK) and polyvinyl alcohol are crosslinked to obtain the polyvinyl alcohol-based composite hydrogel, wherein the SHK has various pharmacological effects including anti-inflammatory, antioxidant, antitumor, antibacterial, antiviral, repairing and the like, and the PVA has stable chemical properties, high water content, good permeability and biocompatibility. According to the invention, SHK and PVA are crosslinked in an alkaline environment, wherein a hydroxyl group on a PVA side chain and a phenolic hydroxyl group in SHK molecules can form a stable and firm hydrogen bond under the alkaline condition, so that SHK is anchored on the PVA molecular chain on the surface of the hydrogel. When the SHK/PVA hydrogel encounters moist environments such as cells and tissues, the SHK/PVA hydrogel swells, hydrogen bonds are opened, SHK existing on the surface of the hydrogel is released into the surrounding environment in the form of molecules of the original medicine, the biological activity effects such as anti-inflammatory, antioxidant and repairing effects are exerted, the purpose of promoting rapid wound healing can be effectively achieved, and the biocompatibility is good.
Drawings
FIG. 1 is a schematic diagram of the hydrogen bonding between SHK and PVA in a SHK/PVA hydrogel;
FIG. 2 is a graphical representation of a split microscope of the SHK/PVA hydrogels obtained in examples 1-3 and the PVA hydrogels obtained in comparative example 1;
FIG. 3 is a schematic diagram of the chemical structural formulas of SHK and Que;
FIG. 4 (a) is a graph showing the comparison of drug contents measured by standard dissolution curves of SHK/PVA hydrogels obtained in examples 1 to 3 in DMSO;
FIG. 4 (b) is a graph showing the comparison of the drug content measured by the standard dissolution curve of Que/PVA hydrogels in DMSO obtained in comparative examples 2 to 4;
FIG. 5 is a graph showing the proliferation state of NIH3T3 cells by SHK/PVA hydrogels obtained in examples 1 to 3 and PVA hydrogels obtained in comparative example 1;
FIG. 6 is a graph showing comparison of activities of SHK/PVA hydrogels obtained in examples 1 to 3 and PVA hydrogels obtained in comparative example 1 on NIH3T3 cells;
FIG. 7 is a graph showing the comparison of wound healing of rats from day 0 to day 14 after the whole layer wound of rats was treated with SHK/PVA hydrogels obtained in examples 1 to 3 and PVA hydrogel obtained in comparative example 1;
FIG. 8 is a graph showing the relative wound area of rats from day 0 to day 14 after the whole layer wound of rats was treated with SHK/PVA hydrogels obtained in examples 1 to 3 and PVA hydrogel obtained in comparative example 1;
FIG. 9 is a graph showing fluorescence contrast between inflammatory factor IL-6 and TNF- α after treatment of defective tissue with SHK/PVA hydrogels obtained in examples 1 to 3 and PVA hydrogel obtained in comparative example 1.
Detailed Description
The technical solutions of the present invention will be clearly and completely described in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Aiming at the fact that single PVA hydrogel does not have bioactivity and antibacterial performance, in the prior art, antibacterial drugs and growth factors are mostly introduced into hydrogel dressing, but the preparation cost and the transportation cost of the hydrogel dressing are too high, and the biocompatibility of the hydrogel dressing is reduced due to the introduction of the antibacterial drugs. Based on the above, the invention provides a polyvinyl alcohol-based composite hydrogel (also called SHK/PVA hydrogel), which is obtained by crosslinking shikonin and polyvinyl alcohol. Wherein the saidShikonin (SHK) is a soluble naphthoquinone compound extracted from radix Arnebiae (traditional Chinese herbal medicine), and has molecular formula of C 16 H 16 O 5 Has various pharmacological effects including anti-inflammatory, antioxidant, antitumor, antibacterial, antiviral and repairing effects, and is gradually applied to the field of tissue engineering. The polyvinyl alcohol (PVA) is a non-toxic and non-immunogenic polymer, has stable chemical properties, high water content, good permeability and biocompatibility, and is also widely used in the field of tissue engineering. The sources of shikonin and polyvinyl alcohol are not particularly limited, and the shikonin and polyvinyl alcohol are commercially available products. Since the degree of polymerization and alcoholysis of the polyvinyl alcohol can affect the mechanical properties of the final prepared hydrogel, in some embodiments of the invention, the degree of polymerization of the polyvinyl alcohol is 1000 to 3000, specifically 1000, 1200, 1500, 1700, 2000, 2200, 2500, 2700, 3000, etc.; the alcoholysis degree is 98-100%, and can be 98%, 98.5%, 99%, 99.5% or 100%. In some embodiments of the invention, the shikonin and polyvinyl alcohol are in a mass ratio of (0-3): (97-100), such as may be 0.1:99.9, 0.5:99.5, 1:99, 1.5:98.5, 2:98, 2.3:97.7, 2.5:97.5, or 3:97, etc. It should be noted that the amount of shikonin is small compared to polyvinyl alcohol, but the amount of shikonin cannot be 0. First, PVA hydrogel has limited surface hydroxyl groups and limited shikonin loading dose. In addition, shikonin is fixed on the surface of the PVA hydrogel, and when the shikonin is applied to tissue injury as a wound dressing, shikonin molecules on the surface of the PVA hydrogel act on the wound surface efficiently, so that the biochemical effect of the shikonin is exerted, and the tissue injury is promoted. The addition amount of shikonin should not be too high in view of cost. Therefore, the grid structure in the SHK/PVA hydrogel provided by the invention is mainly a hydrogen bond structure formed by crosslinking the hydroxyl groups of the polyvinyl alcohol.
According to the invention, SHK and PVA are crosslinked, wherein a hydroxyl group on a PVA side chain and a phenolic hydroxyl group in SHK molecules can form a stable and firm hydrogen bond under alkaline conditions, so that SHK is anchored on a PVA molecular chain on the surface of hydrogel (a schematic diagram is shown in figure 1). When the SHK/PVA hydrogel meets moist environments such as cells and tissues, the SHK/PVA hydrogel absorbs water and swells, hydrogen bonds are opened, SHK existing on the surface of the hydrogel is released into the surrounding environment in the form of original medicine molecules, the biological activity effects such as anti-inflammatory, antioxidant and repairing effects are exerted, and the aim of promoting rapid wound healing can be effectively achieved.
The invention also provides a preparation method of the polyvinyl alcohol-based composite hydrogel, which comprises the following steps:
s1: drying the polyvinyl alcohol solution to obtain polyvinyl alcohol hydrogel;
s2: crosslinking shikonin and the polyvinyl alcohol hydrogel in an alkaline environment to obtain the polyvinyl alcohol-based composite hydrogel.
According to the invention, the polyvinyl alcohol solution is firstly dried to obtain the polyvinyl alcohol hydrogel. The polyvinyl alcohol solution is obtained by mixing polyvinyl alcohol and water, wherein the water can be deionized water, distilled water or ultrapure water. The temperature of the mixing is preferably 80-100 ℃, preferably 90 ℃, and the time is 8-15 h, preferably 10-12 h. The mixing is preferably carried out under stirring. In some embodiments of the present invention, the polyvinyl alcohol solution is dried at 20 to 80 ℃, preferably 30 to 60 ℃, more preferably 40 to 60 ℃, and the drying is stopped based on no significant moisture on the surface of the product, thereby obtaining the polyvinyl alcohol hydrogel. In some embodiments of the present invention, it is preferred that the polyvinyl alcohol solution is poured or coated into a mold and dried at 20 to 80 ℃ to obtain a polyvinyl alcohol film in the form of a hydrogel.
According to the invention, shikonin and polyvinyl alcohol hydrogel are crosslinked in an alkaline environment to obtain the polyvinyl alcohol-based composite hydrogel. In the present invention, the alkaline environment is provided by an alkaline solution selected from any one or more of sodium hydroxide solution, potassium hydroxide solution, ammonia water or sodium ethoxide solution. The alkaline solution is used for dissolving shikonin on one hand and reinforcing the hydrogen bond grid structure in the polyvinyl alcohol hydrogel on the other hand. Since shikonin is self-polymerized in an excessively strong alkaline environment, the alkaline solution is preferably used in the present inventionMiddle OH - The concentration of (2) is controlled to be 0 to 6mol/L, not 0mol/L, but 0.1mol/L, 0.5mol/L, 1mol/L, 2mol/L, 3mol/L, 4mol/L, 5mol/L or 6mol/L, preferably 2 to 5mol/L. In some embodiments of the present invention, shikonin is preferably dissolved in an alkaline solution to obtain an alkaline solution of shikonin, the concentration of the alkaline solution of shikonin in the alkaline solution is 0 to 3200. Mu. Mol/L, and may be 50. Mu. Mol/L, 80. Mu. Mol/L, 100. Mu. Mol/L, 150. Mu. Mol/L, 200. Mu. Mol/L, 400. Mu. Mol/L, 800. Mu. Mol/L, 1000. Mu. Mol/L, 1200. Mu. Mol/L, 1500. Mu. Mol/L, 2000. Mu. Mol/L, 2500. Mu. Mol/L, 3000. Mu. Mol/L, 3200. Mu. Mol/L, etc., and then the polyvinyl alcohol hydrogel or the polyvinyl alcohol film is soaked so that phenolic hydroxyl groups of shikonin and hydroxyl groups in the polyvinyl alcohol hydrogel/film are crosslinked, thereby obtaining a polyvinyl alcohol-based composite hydrogel. The soaking is carried out at room temperature, and the soaking time is 10-60 min, preferably 20-40 min, and more preferably 25-30 min. In some embodiments of the present invention, it is preferable to add an alkaline solution of shikonin to a mold containing the dried polyvinyl alcohol film, and soak for 10 to 60 minutes. Since the crosslinking of shikonin and polyvinyl alcohol is performed in an alkaline environment, in some embodiments of the present invention, it is preferable to further include a washing step after the soaking is completed. The cleaning step specifically comprises the following steps: and cleaning the soaked film with water until the washing liquid is neutral. The purpose of the cleaning is to remove unreacted shikonin and residual alkali liquor so as to facilitate the subsequent practical application of the prepared polyvinyl alcohol-based composite hydrogel.
The preparation method of the polyvinyl alcohol-based composite hydrogel provided by the invention is simple and convenient, has low cost, and can be used for crosslinking the obtained product and shikonin in an alkaline environment after the polyvinyl alcohol solution is dried, so that the preparation method is efficient and quick and is convenient for realizing large-scale production.
In order to explore the universality of the preparation method aiming at plant polyphenol medicaments, quercetin (Que) is adopted to replace Shikonin (SHK) to obtain Que/PVA hydrogel. Through researches, it is found that a certain drug loading rate of Que can be realized in the obtained hydrogel only when the Que with relatively high content is adopted. When the amount of Que added is small, the amount of Que in the resulting hydrogel is too low to be detected. The result shows that compared with Que, the PVA hydrogel provided by the invention is easier to carry SHK, and SHK is the most preferred drug model of the drug carrying method.
The polyvinyl alcohol-based composite hydrogel related to the technical scheme provided by the invention has better capability of promoting cell adhesion and proliferation through in vitro experimental study. Meanwhile, the rat skin defect repair experiment further proves that the prepared polyvinyl alcohol-based composite hydrogel has the capabilities of promoting skin tissue regeneration and accelerating wound healing. And the polyvinyl alcohol-based composite hydrogel has good biocompatibility. Therefore, the invention also provides a wound dressing, which comprises the polyvinyl alcohol-based composite hydrogel related in the technical scheme.
In order to further illustrate the present invention, the following examples are provided. The experimental materials used in the following examples of the present invention are commercially available or prepared according to conventional preparation methods well known to those skilled in the art. Shikonin was purchased from Alatin Biochemical technologies Co., ltd, model S115193.
In the SHK/PVA hydrogels of the following examples, the schematic cross-linking between SHK and PVA is shown in FIG. 1, and it can be seen that the phenolic hydroxyl groups of SHK cross-link with the hydroxyl groups of PVA, and thus SHK is carried in PVA.
Example 1
The present example provides a SHK/PVA hydrogel, the preparation method of which is as follows:
s1: PVA (polymerization degree 1700, alcoholysis degree greater than 99%) was dissolved in deionized water and magnetically stirred overnight at 90℃to give 100mg mL -1 Is a PVA solution of (C). The PVA mixed solution is then poured or coated into a mold and allowed to dry completely at 37 ℃;
s2: a certain amount of SHK was dissolved in a 6M sodium hydroxide solution to prepare a cross-linking solution having a SHK concentration of 80uM, and the SHK cross-linking solution was added to a mold containing the dried PVA film, immersed for 30 minutes, and then washed with water once until the wash solution pH was neutral to wash out the residual lye, obtaining an 80SHK/PVA hydrogel (80 means the molar concentration of SHK in alkaline solution).
Example 2
The present example provides a SHK/PVA hydrogel, the preparation method of which is as follows:
s1: PVA (polymerization degree 1700, alcoholysis degree greater than 99%) was dissolved in deionized water and magnetically stirred overnight at 90℃to give 100mg mL -1 Is a PVA solution of (C). Then pouring or coating the PVA mixed solution into a mould, and completely drying the PVA mixed solution at 35 ℃;
s2: a certain amount of SHK is dissolved in 5M potassium hydroxide solution, a cross-linking solution with SHK concentration of 160uM is prepared, and the SHK cross-linking solution is added into a mold containing a dried PVA film, soaked for 25min, and then washed once with water until the washing solution pH is neutral, so as to wash out the residual lye, and a 160SHK/PVA hydrogel (160 refers to the molar concentration of SHK in alkaline solution) is obtained.
Example 3
The present example provides a SHK/PVA hydrogel, the preparation method of which is as follows:
s1: PVA (polymerization degree 1700, alcoholysis degree greater than 99%) was dissolved in deionized water and magnetically stirred overnight at 90℃to give 100mg mL -1 Is a PVA solution of (C). Then pouring or coating the PVA mixed solution into a mould, and completely drying the PVA mixed solution at 40 ℃;
s2: a certain amount of SHK is dissolved in 6M sodium hydroxide solution, a cross-linking solution with the SHK concentration of 320uM is prepared, the SHK cross-linking solution is added into a mould containing a dried PVA film, soaked for 35min, and then washed once by water until the pH of the washing solution is neutral, so that residual lye is washed off, and 320SHK/PVA hydrogel (320 refers to the molar concentration of SHK in alkaline solution) is obtained.
Comparative example 1
S1: PVA (polymerization degree 1700, alcoholysis degree greater than 99%) was dissolved in deionized water and magnetically stirred overnight at 90℃to give 100mg mL -1 Is a PVA solution of (C). The PVA mixed solution is then poured or coated into a mold and allowed to dry completely at 37 ℃;
s2: preparing a sodium hydroxide solution with the concentration of 6M as a crosslinking solution, adding the crosslinking solution into a mould containing the dried PVA film, soaking for 30min, and then adopting primary water for cleaning until the pH of the washing solution is neutral so as to wash out residual alkali liquor, thereby obtaining the PVA hydrogel.
Comparative example 2
S1: PVA (polymerization degree 1700, alcoholysis degree greater than 99%) was dissolved in deionized water and magnetically stirred overnight at 90℃to give 100mg mL -1 Is a PVA solution of (C). The PVA mixed solution is then poured or coated into a mold and allowed to dry completely at 37 ℃;
s2: quercetin (Que) is dissolved in 6M sodium hydroxide solution, crosslinking solution with the Que concentration of 1600uM is prepared, the Que crosslinking solution is added into a mould containing a dried PVA film, soaked for 30min, and then water is adopted for washing once until the pH of the washing liquid is neutral, so that residual lye is washed off, and 1600Que/PVA hydrogel (1600 refers to the molar concentration of Que in alkaline solution) is obtained.
Comparative example 3
S1: PVA (polymerization degree 1700, alcoholysis degree greater than 99%) was dissolved in deionized water and magnetically stirred overnight at 90℃to give 100mg mL -1 Is a PVA solution of (C). The PVA mixed solution is then poured or coated into a mold and allowed to dry completely at 37 ℃;
s2: quercetin (Que) is dissolved in 6M sodium hydroxide solution, a crosslinking solution with the Que concentration of 320uM is prepared, the Que crosslinking solution is added into a mould containing a dried PVA film, soaked for 30min, and then washed once by water until the pH of the washing solution is neutral, so that residual lye is washed off, and 320Que/PVA hydrogel (320 refers to the molar concentration of Que in alkaline solution) is obtained.
Comparative example 4
S1: PVA (polymerization degree 1700, alcoholysis degree greater than 99%) was dissolved in deionized water and magnetically stirred overnight at 90℃to give 100mg mL -1 Is a PVA solution of (C). The PVA mixed solution is then poured or coated into a mold and allowed to dry completely at 37 ℃;
s2: quercetin (Que) is dissolved in 6M sodium hydroxide solution, a crosslinking solution with the Que concentration of 160uM is prepared, the Que crosslinking solution is added into a mould containing a dried PVA film, soaked for 30min, and then washed once by water until the pH of the washing solution is neutral, so that residual lye is washed off, and 160Que/PVA hydrogel (160 refers to the molar concentration of Que in alkaline solution) is obtained.
Morphology characterization and drug loading test
The hydrogels obtained in examples 1 to 3 and comparative example 1 were subjected to morphology characterization using a bulk microscope, and as shown in fig. 2, it can be seen that SHK was carried in PVA hydrogels in different amounts in the products obtained in examples 1 to 3 as compared with comparative example 1.
The SHK/PVA hydrogels prepared in examples 1 to 3 and the Que/PVA hydrogels prepared in comparative examples 2 to 4 were dissolved by using dimethyl sulfoxide (DMSO), the shikonin and quercetin contents were measured at 520nm by using a multifunctional microplate reader, and the drug loading amounts of the SHK/PVA hydrogels to SHK and Que were measured by comparing standard curves of shikonin and quercetin in DMSO solutions.
The chemical structural formulas of SHK and Que are shown in figure 3, the test result is shown in figure 4 (p is 0.05 is represented by the x), and figure 4 (a) is a comparison graph of drug content measured and calculated by standard dissolution curves of SHK/PVA hydrogels obtained in examples 1-3 in DMSO; FIG. 4 (b) is a graph showing the comparison of the drug content measured by the standard dissolution curve of Que/PVA hydrogels obtained in comparative examples 2 to 4 in DMSO.
As can be seen from FIG. 4 (a), the shikonin with different contents provided in examples 1 to 3 of the present invention was carried in PVA with a drug loading of 1.2 to 2.3wt%. As can be seen from FIG. 4 (b), when treated with 1600. Mu.M Que base cross-linking solution, the drug content of 1600Que/PVA hydrogels was nearly 6%, demonstrating that the drug delivery method of the present invention is equally applicable to Que. However, compared with shikonin, the drug loading amount of the quercetin is relatively low, when PVA hydrogel is treated by 160 mu M of quercetin lye, the content of the quercetin in the hydrogel is too low to be detected, and when the PVA hydrogel is treated by 320 mu M of quercetin lye, the drug loading amount of the hydrogel is about 1.3%. Compared with Que, the PVA hydrogel provided by the invention is easier to carry SHK, which shows that SHK is the most preferable drug model of the drug carrying method.
Proliferation status and Activity test of NIH3T3 cells
NIH3T3 cells are selected to evaluate the adhesion and proliferation states of cells on a single PVA hydrogel and different SHK/PVA hydrogels, and the activity of the cells adhered to the single PVA hydrogel and the different SHK/PVA hydrogels is detected by a cck-8 method.
The test method is as follows:
NIH3T3 cells (2X 10) 4 ) Inoculated into 24-well cell culture plates containing the hydrogel samples obtained in examples 1 to 3 and comparative example 1 while using NIH3T3 cells alone without treatment as a Blank group (i.e., blank group), in CO 2 After culturing in an aseptic cell incubator with a content of 5% and a temperature of 37 ℃ for 3 days, living cells are stained by a fluorescence inversion microscope, and the cell compatibility of the hydrogel is observed.
The test results are shown in fig. 5, and it can be seen that the SHK/PVA hydrogel dressing prepared according to the present invention is advantageous for cell adhesion, and the higher the SHK concentration, the more the number of cells adhered. Meanwhile, on the surface of a single PVA hydrogel, cells are in an agglomerated adhesion state. Cells cultured on the 80SHK/PVA surface are still clustered, but the number of cell clusters adhering to the 80SHK/PVA surface is obviously increased and the size is reduced. In contrast, cells spread in a typical morphology of monodisperse shuttles on 160SHK/PVA and 320SHK/PVA hydrogel surfaces, indicating that the cells remain well active on the material surface. In addition, the cell proliferation efficiency of cells on different SHK/PVA hydrogels is detected by a CCK-8 method, and the result is shown in figure 6 (representing p < 0.05), the absorbance of the SHK/PVA hydrogels at 450nm is obviously higher than that of single PVA hydrogels, and the SHK/PVA hydrogels are close to a blank group, so that the SHK/PVA hydrogel dressing prepared by the invention has the proliferation capacity of obviously promoting NIH3T3 cells, and the higher the SHK content is, the stronger the activity of the NIH3T3 cells is. The TCP group is NIH3T3 cells cultured on TC-treated cell culture plates.
In vivo rat wound healing experiments
The test method is as follows:
the wound healing promoting performance of the drug-loaded PVA hydrogel dressing prepared by the invention is evaluated by adopting a rat back skin full-layer defect model. Animal experiments are all approved by the ethical committee of the national institute of applied chemistry of vinca of academy of sciences of China, and accord with the guidelines for nursing and use of laboratory animals.
SD rats for test (purchased from Liaoning long Biotechnology Co., ltd., 220-250 g) were anesthetized with 1% pentobarbital sodium, and a circular skin defect of 14mm in diameter was formed in the back skin of the rats. Wherein SD rats were randomly grouped into 5 groups according to the following treatment: blank (i.e., blank), PVA, 80SHK/PVA, 160SHK/PVA, 320SHK/PVA, four groups of wounds were covered with 14mm diameter PVA hydrogel, 80SHK/PVA hydrogel, 160SHK/PVA hydrogel, 320SHK/PVA hydrogel, respectively, and the Blank wound was bandaged with sterile gauze. The rats after operation are fed in a single cage, and the activities, diet and health conditions of the rats are observed every day. The wound material was changed every 2 days. Then, after 4, 7, 9, 12 and 14 days after the rat operation, the wound was photographed with a digital camera, and the wound healing was observed and quantitatively analyzed.
The test results are shown in fig. 7-8, and it can be seen that the relative wound area of rats is gradually reduced from day 0 to day 14 by adopting the SHK/PVA hydrogel as the dressing, so that the SHK/PVA hydrogel dressing prepared by the invention can obviously accelerate the wound healing.
Biocompatibility testing
The test method is as follows:
each group of rats was sacrificed on days 3 and 7, and wound tissue specimens were obtained, paraffin-embedded specimens were sectioned approximately 5 μm thick, and immunohistochemical analysis was performed for inflammatory factor IL-6 and TNF- α expression according to the prior study methods.
The test results are shown in fig. 9, and can show that the SHK/PVA hydrogel dressing prepared by the invention can effectively release SHK and obviously down regulate the immune response of tissues, thus indicating that the SHK/PVA hydrogel prepared by the invention has good biocompatibility.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (10)
1. A polyvinyl alcohol-based composite hydrogel is characterized by being obtained by crosslinking shikonin and polyvinyl alcohol.
2. The polyvinyl alcohol-based composite hydrogel according to claim 1, wherein the mass ratio of shikonin to polyvinyl alcohol is (0-3): 97-100.
3. The polyvinyl alcohol-based composite hydrogel according to claim 1, wherein the polyvinyl alcohol has a degree of polymerization of 1000 to 3000;
the alcoholysis degree of the polyvinyl alcohol is 98-100%.
4. The method for producing a polyvinyl alcohol-based composite hydrogel according to any one of claims 1 to 3, comprising the steps of:
s1: drying the polyvinyl alcohol solution to obtain polyvinyl alcohol hydrogel;
s2: crosslinking shikonin and the polyvinyl alcohol hydrogel in an alkaline environment to obtain the polyvinyl alcohol-based composite hydrogel.
5. The method according to claim 4, wherein the drying treatment is carried out at a temperature of 20 to 80 ℃.
6. The method of claim 4, wherein the alkaline environment is provided by an alkaline solution;
the alkaline solution is selected from any one or more of sodium hydroxide solution, potassium hydroxide solution, ammonia water or sodium ethoxide solution;
OH in the alkaline solution - The concentration of (C) is 0-6 mol/L.
7. The method according to claim 4, wherein the crosslinking time is 10 to 60 minutes.
8. The method of claim 4, further comprising a cleaning step after the crosslinking is completed.
9. The method of claim 8, wherein the cleaning agent is water;
the washing is ended when the washing liquid is neutral.
10. A wound dressing comprising the polyvinyl alcohol-based composite hydrogel according to any one of claims 1 to 3 or prepared according to the preparation method of any one of claims 4 to 9.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310561425.9A CN116650709A (en) | 2023-05-17 | 2023-05-17 | Polyvinyl alcohol-based composite hydrogel, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310561425.9A CN116650709A (en) | 2023-05-17 | 2023-05-17 | Polyvinyl alcohol-based composite hydrogel, and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116650709A true CN116650709A (en) | 2023-08-29 |
Family
ID=87725258
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310561425.9A Pending CN116650709A (en) | 2023-05-17 | 2023-05-17 | Polyvinyl alcohol-based composite hydrogel, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116650709A (en) |
-
2023
- 2023-05-17 CN CN202310561425.9A patent/CN116650709A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111662464B (en) | Preparation method of chitosan/sodium alginate double-network hydrogel | |
| Zhang et al. | Graphene oxide-modified electrospun polyvinyl alcohol nanofibrous scaffolds with potential as skin wound dressings | |
| CN108047465B (en) | Methacrylate gelatin/chitosan interpenetrating network hydrogel, preparation method and application | |
| Jing et al. | Alginate/chitosan-based hydrogel loaded with gene vectors to deliver polydeoxyribonucleotide for effective wound healing | |
| NL2026161B1 (en) | Preparation method of 4d chitosan-based thermosensitive hydrogel | |
| Chen et al. | Mussel-inspired ultra-stretchable, universally sticky, and highly conductive nanocomposite hydrogels | |
| CN110152055B (en) | Functional drug sustained-release medical dressing constructed by alginic acid aminated derivative/bacterial cellulose nanocrystalline composite gel | |
| Huang et al. | A tannin-functionalized soy protein-based adhesive hydrogel as a wound dressing | |
| CN110665051A (en) | Preparation method of hemostatic and antibacterial frozen gel stent | |
| CN114316162B (en) | Photo-crosslinking injectable nanofiber-hydrogel compound as well as preparation method and application thereof | |
| WO2021114005A1 (en) | Method of preparing amnion-spongy chitosan composite double-layer wound dressing | |
| CN116650710A (en) | Mussel inspired multifunctional double-network crosslinked hydrogel wound dressing | |
| Lu et al. | Antibacterial cellulose nanocrystal-incorporated hydrogels with satisfactory vascularization for enhancing skin regeneration | |
| Du et al. | Heparin-based sericin hydrogel–encapsulated basic fibroblast growth factor for in vitro and in vivo skin repair | |
| Seifi et al. | A novel multifunctional chitosan-gelatin/carboxymethyl cellulose-alginate bilayer hydrogel containing human placenta extract for accelerating full-thickness wound healing | |
| CN112876694B (en) | Preparation method and application of acrylic acid/epsilon-polylysine adhesive antibacterial hydrogel | |
| CN116650709A (en) | Polyvinyl alcohol-based composite hydrogel, and preparation method and application thereof | |
| CN110917382A (en) | Preparation method of amnion-spongy chitosan composite double-layer wound dressing | |
| CN111840634B (en) | Preparation method and application of grape seed extract hydrogel | |
| Cai et al. | Multifunctional PDA/ZIF8 based hydrogel dressing modulates the microenvironment to accelerate chronic wound healing by ROS scavenging and macrophage polarization | |
| CN113754903A (en) | Preparation method of double-crosslinked hyaluronic acid/chitosan composite hydrogel for skin repair | |
| CN112979999A (en) | Biological macromolecule and modified halloysite composite hydrogel and preparation and application thereof | |
| Zhou et al. | Towards promoting wound healing: A near-infrared light-triggered persistently antibacterial, synergistically hemostatic nanoarchitecture-integrated chitosan hydrogel | |
| CN113069590B (en) | Preparation method of regenerated bacterial cellulose composite hydrogel dressing | |
| CN117180494B (en) | Injectable polysaccharide hydrogel capable of reducing fibrotic scar generation and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |