CN113999630B - Adhesive, and preparation method and application thereof - Google Patents
Adhesive, and preparation method and application thereof Download PDFInfo
- Publication number
- CN113999630B CN113999630B CN202111122756.XA CN202111122756A CN113999630B CN 113999630 B CN113999630 B CN 113999630B CN 202111122756 A CN202111122756 A CN 202111122756A CN 113999630 B CN113999630 B CN 113999630B
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- CN
- China
- Prior art keywords
- hyaluronic acid
- adhesive
- catecholamine
- amine
- polyamide
- 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.)
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- 230000001070 adhesive effect Effects 0.000 title claims abstract description 72
- 239000000853 adhesive Substances 0.000 title claims abstract description 71
- 238000002360 preparation method Methods 0.000 title abstract description 15
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 66
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 65
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 65
- 150000003943 catecholamines Chemical class 0.000 claims abstract description 20
- 238000002156 mixing Methods 0.000 claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 239000012567 medical material Substances 0.000 claims abstract description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 229960003638 dopamine Drugs 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 9
- 230000001590 oxidative effect Effects 0.000 claims description 8
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims description 8
- 239000012298 atmosphere Substances 0.000 claims description 7
- 239000007800 oxidant agent Substances 0.000 claims description 7
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 239000005708 Sodium hypochlorite Substances 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 2
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 13
- 238000012986 modification Methods 0.000 abstract description 5
- 230000004048 modification Effects 0.000 abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 5
- MGBKJKDRMRAZKC-UHFFFAOYSA-N 3-aminobenzene-1,2-diol Chemical group NC1=CC=CC(O)=C1O MGBKJKDRMRAZKC-UHFFFAOYSA-N 0.000 abstract description 4
- 238000010521 absorption reaction Methods 0.000 abstract description 3
- 208000027418 Wounds and injury Diseases 0.000 description 14
- 206010052428 Wound Diseases 0.000 description 13
- 238000007037 hydroformylation reaction Methods 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- 230000003647 oxidation Effects 0.000 description 8
- 238000007254 oxidation reaction Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 239000003106 tissue adhesive Substances 0.000 description 6
- 239000011837 N,N-methylenebisacrylamide Substances 0.000 description 5
- 239000012190 activator Substances 0.000 description 5
- IMUDHTPIFIBORV-UHFFFAOYSA-N aminoethylpiperazine Chemical compound NCCN1CCNCC1 IMUDHTPIFIBORV-UHFFFAOYSA-N 0.000 description 5
- 238000000502 dialysis Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 description 5
- 241000191967 Staphylococcus aureus Species 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- CTENFNNZBMHDDG-UHFFFAOYSA-N Dopamine hydrochloride Chemical compound Cl.NCCC1=CC=C(O)C(O)=C1 CTENFNNZBMHDDG-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 150000001718 carbodiimides Chemical class 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 229960001149 dopamine hydrochloride Drugs 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical group OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000003760 magnetic stirring Methods 0.000 description 2
- 229920000962 poly(amidoamine) Polymers 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000004626 scanning electron microscopy Methods 0.000 description 2
- 238000010008 shearing Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000007718 adhesive strength test Methods 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- VPKDCDLSJZCGKE-UHFFFAOYSA-N carbodiimide group Chemical group N=C=N VPKDCDLSJZCGKE-UHFFFAOYSA-N 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 239000006916 nutrient agar Substances 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229940075469 tissue adhesives Drugs 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
- C09J105/00—Adhesives based on polysaccharides or on their derivatives, not provided for in groups C09J101/00 or C09J103/00
- C09J105/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61L15/225—Mixtures of macromolecular compounds
-
- 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
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0015—Medicaments; Biocides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0036—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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/043—Mixtures of macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Surgery (AREA)
- Hematology (AREA)
- Dispersion Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses an adhesive, a preparation method and application thereof. The adhesive is prepared from the following components: polyamide-amine and catecholamine modified oxidized hyaluronic acid. The adhesive provided by the invention has excellent adhesive strength, water absorption performance and antibacterial performance. The invention prepares the adhesive by introducing the oxidized hyaluronic acid into catecholamine groups for modification and then mixing the oxidized hyaluronic acid with polyamide-amine, and has the advantages of mild preparation method conditions, green and safe, high production efficiency, mass production and the like. The adhesive can be widely applied to the field of medical materials and has wide market prospect.
Description
Technical Field
The invention belongs to the field of materials, and particularly relates to an adhesive and a preparation method and application thereof.
Background
Tissue adhesives are mainly used for wound closure, but no ideal medical adhesive really meets clinical requirements at present. The existing commercialized tissue adhesive has the problems of low or non-adhesion strength with tissue, slow adhesion effect, low biocompatibility, easiness in bacteria breeding and infection of wounds and the like when the wet wound surface is used, and the problems of nondegradability, easiness in gelling and heat release under the wet condition and the like of the existing tissue adhesive cannot well meet the clinical requirement for closed repair of the wet wound surface. Therefore, it is important to develop a new adhesive having antibacterial properties, rapid molding and high adhesive strength.
Hyaluronic acid, a natural extracellular matrix component, is considered to be a very promising tissue adhesive. The existing hyaluronic acid adhesive preparation method adopts an ultraviolet crosslinking technology, but the adhesive prepared by the method has the problems of low mechanical property, low adhesive property and the like, and the ultraviolet irradiation preparation method also has the problems of ultraviolet injury and the like, so that the application of the hyaluronic acid adhesive is limited. Therefore, the existing adhesive has low adhesive strength, is easy to grow bacteria, has poor water absorption and the like, and needs to be solved.
Disclosure of Invention
In order to overcome the problems of the prior art, it is an object of the present invention to provide an adhesive; the second object of the present invention is to provide a method for preparing such an adhesive; it is a further object of the invention to provide the use of such an adhesive.
The inventive concept of the present invention is as follows: the hyaluronic acid is oxidized, catechol group is introduced for modification, and then the modified hyaluronic acid and polyamide-amine are formed into an adhesive, wherein the amino group of the polyamide-amine reacts with the oxidized hyaluronic acid, and the catechol group and the polyamide-amine form a plurality of interactions such as hydrogen bond, pi-pi accumulation and the like, so that the adhesive strength and the antibacterial property of the adhesive can be effectively improved.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
the first aspect of the present invention provides an adhesive prepared from the following components: polyamide-amine and catecholamine modified oxidized hyaluronic acid.
Preferably, the catecholamine includes at least one of dopamine, epinephrine, and norepinephrine; further preferably, the catecholamine is dopamine.
Preferably, the catecholamine-modified oxidized hyaluronic acid is dopamine grafted and aldehyde-formed hyaluronic acid.
Preferably, the structure of the dopamine grafted hydroformylation hyaluronic acid is shown as a formula (I);
in the formula (I), n is a positive integer;
further preferably, in formula (I), n is a positive integer not less than 5.
Preferably, the grafting rate of the dopamine grafted hydroformylation hyaluronic acid is 10% -40%; further preferably, the grafting rate of the dopamine grafted and hydroformylation hyaluronic acid is 15% -35%; still further preferably, the dopamine grafted hydroformylation hyaluronic acid has a grafting ratio of 20% -31%.
Preferably, the polyamide-amine is a hyperbranched polyamide-amine.
Preferably, the mass ratio of the polyamide-amine to catecholamine modified oxidized hyaluronic acid is 1: (2-10); further preferably, the mass ratio of the polyamide-amine to catecholamine modified oxidized hyaluronic acid is 1: (2-8); still further preferably, the mass ratio of the polyamide-amine to catecholamine-modified oxidized hyaluronic acid is 1: (2-5).
A second aspect of the present invention provides a method for preparing the adhesive according to the first aspect of the present invention, comprising the steps of:
1) Oxidizing hyaluronic acid to obtain oxidized hyaluronic acid;
2) Mixing and reacting the oxidized hyaluronic acid with catecholamine to obtain catecholamine modified oxidized hyaluronic acid;
3) And mixing catecholamine modified oxidized hyaluronic acid with polyamide-amine for reaction to obtain the adhesive.
Preferably, the oxidation of step 1) is performed by mixing hyaluronic acid with an oxidizing agent.
Preferably, the oxidant comprises at least one of sodium periodate, hydrogen peroxide, nitric acid and sodium hypochlorite; still further preferably, the oxidizing agent is sodium periodate.
Preferably, the molar ratio of hyaluronic acid to oxidant is 1: (100-600); further preferably, the molar ratio of hyaluronic acid to oxidant is 1: (230-460).
Preferably, the oxidation time in the step 1) is 3-7 h; further preferably, the oxidation time in step 1) is 4h to 6h.
Preferably, the oxidation temperature in step 1) is 10 ℃ to 40 ℃; further preferably, the oxidation temperature in step 1) is 20 ℃ to 30 ℃; still further preferred, the oxidation temperature in step 1) is 25 ℃.
Preferably, the oxidation in step 1) is carried out under light-shielding conditions.
Preferably, the oxidation in step 1) further comprises a step of adding a reducing agent to terminate the reaction.
Preferably, the reducing agent comprises an alcohol; further preferably, the reducing agent comprises at least one of ethanol, propanol, ethylene glycol, and glycerol; still further preferably, the reducing agent is ethylene glycol.
Preferably, the mixing of step 2) meets at least one of the following conditions:
the oxidized hyaluronic acid participates in the reaction in the mode of oxidized hyaluronic acid solution, and the pH value of the oxidized hyaluronic acid solution is 4-5;
the mixed atmosphere is an inert gas atmosphere;
the mass ratio of the oxidized hyaluronic acid to catecholamine is 1: (0.25-2).
Further preferably, the oxidized hyaluronic acid participates in the reaction in the form of an oxidized hyaluronic acid solution, and the pH value of the oxidized hyaluronic acid solution is 4-5; still further preferably, the pH of the oxidized hyaluronic acid solution is 4.4-4.8.
Further preferably, the mass ratio of the oxidized hyaluronic acid to catecholamine is 1: (0.25-2); still further preferably, the mass ratio of the oxidized hyaluronic acid to catecholamine is 1: (0.4-1.6); still more preferably, the mass ratio of the oxidized hyaluronic acid to catecholamine is 1: (0.5-1.2).
Further preferably, the mixed atmosphere is an inert gas atmosphere; still more preferably, the mixed atmosphere is a nitrogen atmosphere.
Preferably, the reaction temperature in the step 2) is 10-40 ℃; further preferably, the reaction temperature in step 2) is 20 ℃ to 30 ℃.
Preferably, the reaction time in the step 2) is 12-36 h; it is further preferred that the reaction time in step 2) is 18h to 30h.
Preferably, the step 2) further comprises the step of adding an activator to activate the oxidized hyaluronic acid before mixing.
Preferably, the activator is an amine activator; further preferably, the activator includes at least one of carbodiimide (EDC), N-hydroxysuccinimide (NHS).
Preferably, when the activator is a carbodiimide and an N-hydroxysuccinimide, the molar ratio of the carbodiimide to the N-hydroxysuccinimide is 1 (0.3-1); further preferably, the molar ratio of the carbodiimide to the N-hydroxysuccinimide is 1 (0.4-0.7).
Preferably, step 2) further comprises a purification step of dialysis after the mixing reaction.
Preferably, the dialysis has a molecular weight cut-off of 3000Da to 4000Da; further preferably, the dialysis has a molecular weight cut-off of 3400Da to 3600Da.
Preferably, the polyamide-amine (HPMA) is obtained by polymerization of N, N-Methylenebisacrylamide (MBA) and 1- (2-aminoethyl) piperazine (AEPZ); further preferably, the polyamide-amine is obtained from N, N-methylenebisacrylamide and 1- (2-aminoethyl) piperazine by Michael addition reaction.
Preferably, the mass ratio of the N, N-methylene bisacrylamide to the 1- (2-aminoethyl) piperazine is 1: (0.6-1.2); still further preferably, the mass ratio of the N, N-methylenebisacrylamide to the 1- (2-aminoethyl) piperazine is 1: (0.8-0.9).
Preferably, the reaction temperature is 20 ℃ to 40 ℃; further preferably, the polymerization temperature is 25℃to 35 ℃.
Preferably, the reaction time is 40h-80h; further preferably, the polymerization time is 52h to 68h.
A third aspect of the invention provides the use of an adhesive according to the first aspect of the invention in the field of medical materials.
Preferably, the medical material comprises a drug sustained release carrier and a wound dressing.
The beneficial effects of the invention are as follows:
the adhesive provided by the invention has excellent adhesive strength, water absorption performance and antibacterial performance. The invention prepares the adhesive by introducing the oxidized hyaluronic acid into catecholamine groups for modification and then mixing the oxidized hyaluronic acid with polyamide-amine, and has the advantages of mild preparation method conditions, green and safe, high production efficiency, mass production and the like. The adhesive can be widely applied to the field of medical materials and has wide market prospect.
In particular, the invention has the following advantages:
1) The adhesive provided by the invention is sponge in a dry state, has an optimal use effect, is unlimited in storage condition, does not need to be dissolved before use, can quickly absorb liquid of a moist wound surface by a spongy loose porous structure when the adhesive is used on the moist wound surface, so that the contacted moist wound surface can quickly form a dry wound surface, and meanwhile, dopamine and aldehyde groups in the sponge porous structure can be bonded with amino groups of wound surface tissues, so that the adhesive has stronger tissue adhesive strength and is favorable for bonding and plugging the wound surface.
2) The preparation method provided by the invention has the advantages of mild condition, environment friendliness, safety, high production efficiency and mass production, and is prepared by introducing the hyaluronic acid into catecholamine groups for modification and then mixing the catecholamine groups with polyamide-amine to obtain the adhesive.
3) The adhesive provided by the invention can be quickly glued within 10 seconds, can quickly absorb water in a seepage environment, and has obvious use advantages; the hyperbranched polyamide-amine with antibacterial property is added into the adhesive, the adhesive has excellent antibacterial property, particularly has better antibacterial property on staphylococcus aureus, and the adhesive can keep wounds to heal in a sterile and moist environment; the adhesive provided by the invention has excellent adhesive strength, and can be widely applied to the field of medical materials, in particular to a drug slow release carrier and a wound dressing.
Drawings
FIG. 1 is a diagram showing the reaction scheme for preparing dopamine-grafted hydroformylation hyaluronic acid according to example 1.
FIG. 2 is a diagram of the reaction scheme for preparing hyperbranched polyamidoamine according to example 1.
FIG. 3 is a diagram of the reaction scheme for preparing an adhesive according to example 1.
FIG. 4 is a scanning electron microscope image of the adhesive prepared in example 1.
Detailed Description
Specific implementations of the invention are further described below with reference to the drawings and examples, but the implementation and protection of the invention are not limited thereto. It should be noted that the following processes, if not specifically described in detail, can be realized or understood by those skilled in the art with reference to the prior art. The reagents or instruments used did not identify the manufacturer and were considered conventional products available commercially.
Example 1
The procedure for the preparation of the adhesive of this example is as follows:
1) Preparation of dopamine-grafted hydroformylation hyaluronic acid (DA-OHA):
FIG. 1 is a diagram showing the reaction scheme for preparing dopamine-grafted hydroformylation hyaluronic acid according to example 1. Preparing 100mL of sodium hyaluronate aqueous solution with the mass concentration of 1% and completely dissolving by magnetic stirring, then adding 5mL of sodium periodate aqueous solution with the mass concentration of 2%, stirring the mixed solution for 3h at room temperature under the dark condition, then adding 0.1mL of ethylene glycol to terminate the reaction, continuing stirring for 1h, and performing ethanol precipitation dialysis on the obtained product of aldehyde hyaluronic acid (OHA) and freeze-drying for later use.
100mL of 1% strength by mass hydroformylation hyaluronic acid (OHA) was prepared with a pH=4.4-4.8 buffer, and dissolved by magnetic stirring to form a clear solution. EDC & HCl (carbodiimide hydrochloride) and NHS (N-hydroxysuccinimide) with a molar ratio of 2:1 were then added for 30min at room temperature. The pH of the reaction mixture was maintained at 4.4-4.8. 1.2g of dopamine hydrochloride was then added to the reaction under nitrogen, the mixture was stirred at room temperature for 24h. After the completion of the reaction, the reaction mixture was dialyzed against 0.01mol/L aqueous hydrochloric acid (MWCO=3500 Da) and then dialyzed against distilled water, whereby unreacted dopamine hydrochloride was removed by dialysis. Spongy white solid dopamine-grafted hydroformylation hyaluronic acid (DA-OHA) was obtained by lyophilization. The grafting rate of the dopamine grafted aldehyde hyaluronic acid is 31 percent.
2) Preparation of hyperbranched polyamide-amine (HPMA):
FIG. 2 is a diagram of the reaction scheme for preparing hyperbranched polyamidoamine according to example 1. N, N-Methylene Bisacrylamide (MBA) is dispersed in ultrapure water to prepare 30mL of MBA aqueous solution with mass concentration of 10%, then 2.58g of 1- (2-aminoethyl) piperazine (AEPZ) is added dropwise, the MBA aqueous solution gradually becomes a pale yellow clear solution, the bath is kept at a constant temperature of 30 ℃, the solution is stirred vigorously for 60 hours, the product is precipitated by acetone, and the product is centrifugally freeze-dried for standby.
3) Preparation of the adhesive:
FIG. 3 is a diagram of the reaction scheme for preparing an adhesive according to example 1. 100uL of DA-OHA aqueous solution with the mass concentration of 20% and 100uL of HPMA aqueous solution with the mass concentration of 10% are uniformly mixed at room temperature, and the mixture can be glued within 10 seconds to obtain the adhesive.
Example 2
In the preparation process of the adhesive, the adding amount of the dopamine hydrochloride in the step 1) is reduced from 1.2g to 0.5g, and the grafting rate of the prepared dopamine grafted hydroformylation hyaluronic acid is 20%. The remaining steps are exactly the same as in example 1.
Performance testing
1. Adhesive strength test
The adhesives prepared in examples 1-2 were subjected to an adhesion strength test to determine the strength properties of the tissue adhesive in the lap shear state by tensile loading following the standard test procedure ASTM F2255-2005, the specific test procedure being as follows:
two fresh pigskin pieces (20 mm. Times.60 mm in area) were treated to remove fat layer, and soaked in PBS 7.4 for 30min before application. Respectively taking 200uL of DA-OHA with the mass concentration of 2% and uniformly coating the DA-OHA on the surface of a fresh pigskin, uniformly coating 200uL of HPMA with the mass concentration of 10% on the surface of the pigskin on the other side, overlapping the coating parts of the two pigskins, wherein the overlapping area is 20mm multiplied by 20mm, pressing the pigskin for 30min by using a 200g weight, testing by using a universal testing machine, testing the clamping head at the speed of 1mm/min until a sample is destroyed, and the overlapping shearing strength is the overlapping shearing force of unit area, wherein the unit is: and kPa. The test results show that the adhesive prepared in example 1 has an adhesive strength of 89.60.+ -. 6.2kPa; the adhesive prepared in example 2 had an adhesive strength of 39.77.+ -. 8.4kPa, indicating that the adhesive provided by the present invention has excellent adhesive strength.
2. Antibacterial property test
The adhesive prepared in the examples 1-2 was subjected to antibacterial performance test, and the antibacterial effect of the gel on the strain to be tested (staphylococcus aureus) was measured by using an agar diffusion paper sheet method and a colony counting method, and the specific test steps were as follows:
preparation of the composition containing 1X 10 8 The bacterial suspension of the strain to be tested is uniformly coated on the surface of a solid nutrient agar culture medium flat plate, and each flat plate is coated with 100 mu L. The adhesive prepared by the invention is uniformly coated on the surface of the sterilized and dried filter paper sheet under the aseptic condition to be used as a gel paper sheet. The prepared adhesive paper sheet (with the sterilized filter paper sheet as a blank) was attached to the surface of the flat plate. Four paper sheets were placed on each plate for biological repetition and incubated at 37℃for 24h. 1mL of diluted bacterial suspension is taken on a flat plate, the flat plate is poured with agar, the mixture is uniformly mixed, after solidification, the mixture is inverted and cultured in a constant temperature box at 37 ℃ for 24 hours, and the total number of bacterial colonies is calculated by referring to GB 4789.2-2016.
Antibacterial ratio R/% = (total number of control colonies-total number of binder colonies)/total number of control colonies×100.
The test result shows that the antibacterial rate of the adhesive prepared in the example 1 to staphylococcus aureus can reach 90 percent, and the antibacterial rate of the adhesive prepared in the example 2 to staphylococcus aureus can reach 99 percent.
3. Characterization test
The lyophilized xerogel of example 1 was subjected to scanning electron microscopy and FIG. 4 is a scanning electron microscopy image of the adhesive prepared in example 1. As can be seen from FIG. 4, the adhesive prepared by the present invention has a complex network structure, and is an adhesive with excellent structure and performance.
The foregoing examples are illustrative of the present invention and are not intended to be limiting, and other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principles of the invention are intended to be equivalent in scope.
Claims (8)
1. An adhesive, characterized in that: the adhesive is prepared from the following components: polyamide-amine and catecholamine modified oxidized hyaluronic acid;
the catecholamine modified oxidized hyaluronic acid is dopamine grafted aldehyde hyaluronic acid;
the grafting rate of the dopamine grafted aldehyde hyaluronic acid is 20% -31%.
2. The adhesive of claim 1, wherein: the structure of the dopamine grafted aldehyde hyaluronic acid is shown as a formula (I);
in the formula (I), n is a positive integer.
3. The adhesive of claim 1, wherein: the polyamide-amine is a hyperbranched polyamide-amine.
4. The adhesive of claim 1, wherein: the mass ratio of the polyamide-amine to catecholamine modified oxidized hyaluronic acid is 1: (2-10).
5. A method of preparing the adhesive of any one of claims 1-4, wherein: the method comprises the following steps:
1) Oxidizing hyaluronic acid to obtain oxidized hyaluronic acid;
2) Mixing and reacting the oxidized hyaluronic acid with catecholamine to obtain catecholamine modified oxidized hyaluronic acid;
3) And mixing catecholamine modified oxidized hyaluronic acid with polyamide-amine for reaction to obtain the adhesive.
6. The method of manufacturing according to claim 5, wherein: step 1) oxidizing to obtain hyaluronic acid and an oxidant for mixed reaction; the oxidant comprises at least one of sodium periodate, hydrogen peroxide, nitric acid and sodium hypochlorite.
7. The method of manufacturing according to claim 5, wherein: step 2) the mixing meets at least one of the following conditions:
the oxidized hyaluronic acid participates in the reaction in the mode of oxidized hyaluronic acid solution, and the pH value of the oxidized hyaluronic acid solution is 4-5;
the mixed atmosphere is an inert gas atmosphere;
the mass ratio of the oxidized hyaluronic acid to catecholamine is 1: (0.25-2).
8. Use of the adhesive according to any one of claims 1-4 in the field of medical materials.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103648536A (en) * | 2011-04-05 | 2014-03-19 | 弗赖堡大学医院 | Biocompatible and biodegradable gradient layer system for regenerative medicine and for tissue support |
| CN106336829A (en) * | 2016-09-07 | 2017-01-18 | 江南大学 | Preparation method for DA (Dopamine)-based adhesive |
| CN111875822A (en) * | 2020-08-18 | 2020-11-03 | 杭州仪文生物医药有限公司 | Bi-component cross-linked composite material applied to plastic surgery and preparation method thereof |
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| KR102010051B1 (en) * | 2017-09-20 | 2019-08-12 | 주식회사 포스코 | Coacervate formed from catechol conjugated anionic polymer, and adhesive comprising thereof and method for preparing the same |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103648536A (en) * | 2011-04-05 | 2014-03-19 | 弗赖堡大学医院 | Biocompatible and biodegradable gradient layer system for regenerative medicine and for tissue support |
| CN106336829A (en) * | 2016-09-07 | 2017-01-18 | 江南大学 | Preparation method for DA (Dopamine)-based adhesive |
| CN111875822A (en) * | 2020-08-18 | 2020-11-03 | 杭州仪文生物医药有限公司 | Bi-component cross-linked composite material applied to plastic surgery and preparation method thereof |
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| Title |
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| 树枝状聚酰胺-胺的合成及应用;王学川;何林燕;袁绪政;;现代化工(第08期);第86-89页 * |
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