CN117065080A - Medical adhesive and preparation method thereof - Google Patents
Medical adhesive and preparation method thereof Download PDFInfo
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- CN117065080A CN117065080A CN202210505890.6A CN202210505890A CN117065080A CN 117065080 A CN117065080 A CN 117065080A CN 202210505890 A CN202210505890 A CN 202210505890A CN 117065080 A CN117065080 A CN 117065080A
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- medical adhesive
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- carbon double
- double bond
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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 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 36
- 125000000524 functional group Chemical group 0.000 claims abstract description 20
- 229920006295 polythiol Polymers 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 13
- 229920003232 aliphatic polyester Polymers 0.000 claims abstract description 10
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 46
- 239000000463 material Substances 0.000 claims description 29
- 239000000243 solution Substances 0.000 claims description 24
- -1 functional group compound Chemical class 0.000 claims description 17
- 239000000178 monomer Substances 0.000 claims description 12
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 11
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 claims description 8
- IMQFZQVZKBIPCQ-UHFFFAOYSA-N 2,2-bis(3-sulfanylpropanoyloxymethyl)butyl 3-sulfanylpropanoate Chemical compound SCCC(=O)OCC(CC)(COC(=O)CCS)COC(=O)CCS IMQFZQVZKBIPCQ-UHFFFAOYSA-N 0.000 claims description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 6
- 150000002430 hydrocarbons Chemical group 0.000 claims description 6
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 6
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 6
- IGAWKPMXUGZZIH-UHFFFAOYSA-N 2-prop-2-enoyloxyethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCOC(=O)C=C IGAWKPMXUGZZIH-UHFFFAOYSA-N 0.000 claims description 5
- OKKRPWIIYQTPQF-UHFFFAOYSA-N Trimethylolpropane trimethacrylate Chemical compound CC(=C)C(=O)OCC(CC)(COC(=O)C(C)=C)COC(=O)C(C)=C OKKRPWIIYQTPQF-UHFFFAOYSA-N 0.000 claims description 3
- PDNOURKEZJZJNZ-UHFFFAOYSA-N [4-(bromomethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(CBr)C=C1 PDNOURKEZJZJNZ-UHFFFAOYSA-N 0.000 claims description 3
- 229960003638 dopamine Drugs 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- ZODNDDPVCIAZIQ-UHFFFAOYSA-N (2-hydroxy-3-prop-2-enoyloxypropyl) 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCC(O)COC(=O)C=C ZODNDDPVCIAZIQ-UHFFFAOYSA-N 0.000 claims description 2
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 claims description 2
- HAQZWTGSNCDKTK-UHFFFAOYSA-N 2-(3-sulfanylpropanoyloxy)ethyl 3-sulfanylpropanoate Chemical compound SCCC(=O)OCCOC(=O)CCS HAQZWTGSNCDKTK-UHFFFAOYSA-N 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 12
- 230000002209 hydrophobic effect Effects 0.000 abstract description 9
- 238000002791 soaking Methods 0.000 abstract description 6
- 238000010276 construction Methods 0.000 abstract description 2
- 238000011010 flushing procedure Methods 0.000 abstract description 2
- 239000011347 resin Substances 0.000 abstract description 2
- 229920005989 resin Polymers 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- 229920001610 polycaprolactone Polymers 0.000 description 15
- 239000004632 polycaprolactone Substances 0.000 description 15
- 239000002244 precipitate Substances 0.000 description 15
- 238000001556 precipitation Methods 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000001291 vacuum drying Methods 0.000 description 9
- 238000004821 distillation Methods 0.000 description 8
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 8
- 206010052428 Wound Diseases 0.000 description 7
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000002390 rotary evaporation Methods 0.000 description 4
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 4
- QZQIWEZRSIPYCU-UHFFFAOYSA-N trithiole Chemical compound S1SC=CS1 QZQIWEZRSIPYCU-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical group OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000002861 polymer material Substances 0.000 description 3
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
- 206010048038 Wound infection Diseases 0.000 description 2
- 125000003172 aldehyde group Chemical group 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 239000000227 bioadhesive Substances 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- 150000004662 dithiols Chemical class 0.000 description 2
- 239000012949 free radical photoinitiator Substances 0.000 description 2
- 229920006150 hyperbranched polyester Polymers 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 239000012948 isocyanate Chemical group 0.000 description 2
- 150000002513 isocyanates Chemical group 0.000 description 2
- 239000010985 leather Substances 0.000 description 2
- 239000011344 liquid material Substances 0.000 description 2
- VHRYZQNGTZXDNX-UHFFFAOYSA-N methacryloyl chloride Chemical compound CC(=C)C(Cl)=O VHRYZQNGTZXDNX-UHFFFAOYSA-N 0.000 description 2
- 238000005935 nucleophilic addition reaction Methods 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical group O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- VYMPLPIFKRHAAC-UHFFFAOYSA-N 1,2-ethanedithiol Chemical compound SCCS VYMPLPIFKRHAAC-UHFFFAOYSA-N 0.000 description 1
- 239000012956 1-hydroxycyclohexylphenyl-ketone Substances 0.000 description 1
- OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 description 1
- GNCJRTJOPHONBZ-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1h-imidazole Chemical compound CC1(C)NC=NC1(C)C GNCJRTJOPHONBZ-UHFFFAOYSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical group SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- 208000031737 Tissue Adhesions Diseases 0.000 description 1
- 125000004018 acid anhydride group Chemical group 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M acrylate group Chemical group C(C=C)(=O)[O-] NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 238000007718 adhesive strength test Methods 0.000 description 1
- 150000008064 anhydrides Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000003364 biologic glue Substances 0.000 description 1
- MQDJYUACMFCOFT-UHFFFAOYSA-N bis[2-(1-hydroxycyclohexyl)phenyl]methanone Chemical compound C=1C=CC=C(C(=O)C=2C(=CC=CC=2)C2(O)CCCCC2)C=1C1(O)CCCCC1 MQDJYUACMFCOFT-UHFFFAOYSA-N 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 208000028831 congenital heart disease Diseases 0.000 description 1
- 238000001723 curing Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Chemical compound CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 230000009477 glass transition Effects 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 239000012943 hotmelt Substances 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical group OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 239000003894 surgical glue Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 238000009864 tensile test Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G75/00—Macromolecular compounds obtained by reactions forming a linkage containing sulfur with or without nitrogen, oxygen, or carbon in the main chain of the macromolecule
- C08G75/02—Polythioethers
- C08G75/04—Polythioethers from mercapto compounds or metallic derivatives thereof
- C08G75/045—Polythioethers from mercapto compounds or metallic derivatives thereof from mercapto compounds and unsaturated 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
- 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
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Surgery (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
Abstract
The invention discloses a medical adhesive and a preparation method thereof. The medical adhesive comprises the reaction product of the following raw materials: 30% -55% of a compound of a polythiol functional group; 20-30 mole percent of compound with multi-carbon double bond functional groups; 20% -45% by mole of an adhesive compound; 0.001% -0.05% of catalyst. The medical adhesive takes hydrophobic aliphatic polyester as main resin and contains hydrophilic adhesion functional groups. The method has the advantages of strong operability in the actual use process, simple construction method, good adhesion performance and water soaking and flushing resistance.
Description
Technical Field
The invention belongs to the field of biomedical materials, and particularly relates to a medical adhesive and a preparation method thereof.
Background
Billions of suture operations are performed annually worldwide to close wounds or surgical incisions. Improper wound treatment not only results in slow healing but also can cause wound infection, which in severe cases can even be life threatening to the patient. However, the suture wound has complex operation and poor sealing property, and is easy to leak body fluid and cause infection. To solve the above problems, a specific polymer material is stuck to a wound site as an adhesive, which can effectively stop bleeding, seal a wound, prevent infection and promote wound healing. The medical adhesive has simple use method, improves the nursing quality, is not easy to generate scars, and is particularly suitable for the fields of surgery, dentistry, plastic cosmetology and the like.
Ideally, the medical adhesive is a liquid material that hardens the assembly after application to the wound surfaceThe fabrics are bonded together. And the surface of the biological tissue is rich in a large number of active groups (such as-NH) 2 The materials containing adhesion groups such as succinimide, aldehyde group, isocyanate, anhydride and catechol can achieve a strong tissue adhesion effect. To achieve the above object, the preparation of aqueous bioadhesives by dispersing functional polymeric materials in water is currently a common method in the art. The aqueous medical adhesive is poor in water adhesion due to inherent hydrophilicity and is not resistant to water washing. In addition, aqueous adhesives are also prone to fouling and bacterial attack on the body surface, causing wound infections. Based on the above problems, the university of Harvey medical institute (Ablood-resistant surgical glue for minimally invasive repair of vessels and heart defects [ J)]Sci.Transl.Med.,2014,6 (218): 218ra 6) a non-aqueous bioadhesive based on a hydrophobic aliphatic polyester material was developed. The hydrophobic adhesive material is itself in a liquid state, adheres to tissue under water, and resists water-washing. The adhesive material is an acrylate group with a hydrophobic end group, and the chain segment is aliphatic polyester containing eight methylene groups. The adhesive material hardens under light irradiation, thereby bonding the objects together. However, the light curing method is often limited by complex surface contours of the wound, poor light penetration, insufficient hardening adhesion, and reduced adhesion. In addition, the adhesive material lacks an adhesive functional group, and has poor adhesion effect to biological tissues. While the university of Jiangnan (CN 202010268527.8, CN202010271866.1 and CN 202011049135.9) develops a liquid polymer material which takes hydrophobic hyperbranched polythioether as a framework and takes hydrophobic thiol groups as terminal groups, and then the liquid polymer material and polyethylene glycol materials which respectively take acrylic ester, isocyanate and benzaldehyde as terminal groups are mixed to develop the non-aqueous polyether type biological adhesive which is light-cured, double-component mixed-cured and hot melt injected. However, the hydrophilic polyethylene glycol material contained in the adhesive may impair the adhesive effect and water resistance of the adhesive in water. Moreover, the adhesive material often suffers from uneven mixing of components, poor operability in actual use, narrow operation window, and the like in use.
Disclosure of Invention
In order to solve the defects and the shortcomings existing in the prior art, the invention provides the medical adhesive which has good tissue bonding effect, strong practical use operability and water resistance and the preparation method thereof. In order to achieve the aim of the invention, the adhesive material takes hydrophobic hyperbranched polyester as a framework structure and has hydrophilic adhesion groups modified on molecular chain side groups or end groups, thereby achieving the effect.
As one aspect of the present invention, the present invention provides the following technical solutions:
a medical adhesive comprising the reaction product of:
30-55 mole percent of polythiol functional group compound;
20-30 mole percent of compound with multiple carbon-carbon double bond functional groups;
20-45 mole percent of an adhesive compound;
0.001 to 0.05 mole percent of catalyst.
As a preferred embodiment, the medical adhesive comprises the reaction product of:
30-55 mol% of linear or multi-arm aliphatic polyester macromolecular monomer which takes the combination of saturated hydrocarbon chains containing five to ten carbons and ester bonds as a repeating unit and has the molecular weight of 500-2000 g/mol, wherein the end group is a mercaptan group;
20-30 mole percent of compound with multiple carbon-carbon double bond functional groups;
20-45 mole percent of an adhesive compound;
0.001 to 0.05 mole percent of catalyst.
As another preferred embodiment, the medical adhesive comprises the reaction product of:
30-55 mole percent of polythiol functional group compound;
20-30 mol% of linear or multi-arm aliphatic polyester macromolecular monomers with end groups of carbon-carbon double bond groups, a combination of saturated hydrocarbon chains containing five to ten carbons and ester bonds as a repeating unit and a molecular weight of 500-2000 g/mol;
20-45 mole percent of an adhesive compound;
0.001 to 0.05 mole percent of catalyst.
A preparation method of a medical adhesive comprises the following steps:
(1) Dissolving a compound with a polythiol functional group in an organic solvent, adding a catalyst, adding a compound with a multi-carbon double bond functional group, and reacting for 3-24 hours;
(2) Adding an adhesive compound into the reaction solution obtained in the step (1) for reaction for 6-24 hours.
As a preferable mode, the method of the invention further comprises (3) purifying the reaction liquid obtained in the step (2).
The compound with the polythiol functional group is a linear or multi-arm aliphatic polyester macromolecular monomer which has more than two thiol groups per molecule, has a molecular weight of less than 500g/mol, takes a small molecular monomer or a terminal group as a thiol group, takes a combination of a saturated hydrocarbon chain containing five to ten carbons and an ester bond as a repeating unit, and has a molecular weight of 500 to 2000 g/mol.
As a preferred embodiment, the polythiol functional compound is a polythiol functional compound having two or three thiol groups per molecule, such as ethylene dithiol, ethylene glycol bis (3-mercaptopropionate), trimethylolpropane tris (3-mercaptopropionate), or a compound of formula I:
wherein m=5 to 10, n=5 to 30, and at least two R 3 A group.
The compound with multiple carbon-carbon double bond functional groups is a small molecular monomer with more than two carbon-carbon double bonds per molecule and molecular weight less than 500g/mol, or a linear or multi-arm aliphatic polyester macromolecular monomer with a terminal group of carbon-carbon double bond groups, a combination of saturated hydrocarbon chains containing five to ten carbons and ester bonds as a repeating unit and molecular weight of 500-2000 g/mol.
As a preferred embodiment, the compound having a multi-carbon double bond functional group is a compound having two or three carbon-carbon double bonds per molecule, such as 3- (acryloyloxy) -2-hydroxypropyl methacrylate, 2- (acryloyloxy) ethyl methacrylate, trimethylolpropane trimethacrylate, or a compound of formula II:
wherein x=5 to 10, y=5 to 30, and there are at least 2R 6 A group.
The adhesive compound of the present invention refers to a compound containing both a thiol-reactive group including a carbon-carbon double bond, a halogen functional group, and the like, and an adhesive group including an acid anhydride group, a succinimidyl ester group, an aldehyde group, a phenylboronic acid group, a catechol group, and the like.
As a preferred embodiment, the adhesive compound of the present invention is selected from one or more of maleic anhydride, 4-bromomethylphenylboronic acid, 3-acrylamido dopamine.
The catalysts of the present invention include, but are not limited to, free radical thermal initiators commonly used in thiol-ene addition reactions, such as; azobisisobutyronitrile, benzoyl peroxide, free radical photoinitiators, such as; benzophenone, 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropenone, 2-hydroxy-2-methyl-1-phenylpropion, 1-hydroxycyclohexylphenyl ketone, and the like, nucleophilic addition catalysts such as: triethylamine, triethylphosphorus, triphenylphosphine, tetramethylimidazole, and the like.
Wherein, the compound with polythiol functional group and the compound with multi-carbon double bond functional group are preferably selected to match, one with 2 degrees of functionality and one with 3 degrees of functionality, and one with small molecular monomer and one with large molecular monomer.
Wherein, when the catalyst is a free radical thermal initiator, the reaction condition is 50-100 ℃; when the catalyst is a free radical photoinitiator, the reaction condition is room temperature reaction under ultraviolet irradiation; when the catalyst is a nucleophilic addition catalyst, the reaction condition is room temperature.
The organic solvent includes, but is not limited to, one or more of N' N-dimethylformamide solution, acetonitrile, tetrahydrofuran, dichloromethane and the like.
As a preferred embodiment, the purification comprises the steps of: concentrating the reaction solution obtained in the step (2), adding a small amount of reaction solvent for redissolving, then dripping into absolute methanol for precipitation, taking the precipitate, repeating the dissolving-precipitating operation, and drying the precipitate in vacuum to obtain the adhesive.
The medical adhesive of the invention is in liquid state at room temperature, and the glass transition temperature is-60 to-20 ℃.
Wherein the chemical structure of the adhesive takes hydrophobic hyperbranched polyester as a framework and is modified with hydrophilic adhesive groups. The binder may cure the bonded object by spontaneously hydrophilic and hydrophobic association between the polymer segments.
As another aspect of the present invention, there is also provided a medical adhesive, which is prepared according to the method of preparing a medical adhesive as described in any one of the above.
The invention has the following beneficial effects:
(1) The adhesive provided by the invention is a water-insoluble liquid material, can directly bond biological tissues in water environment and can resist soaking and flushing of body fluid.
(2) The adhesive provided by the invention uses the aliphatic polyester material as the main resin, and the chemical structure of the adhesive contains a large number of hydrophilic adhesion functional groups, so that the adhesive has good adhesion performance to tissues.
(3) After the adhesive provided by the invention is coated on an object in a water environment, the adhesive can be spontaneously crosslinked and hardened through hydrophilic-hydrophobic association, so that the adhesive has strong operability in the actual use process and simple construction method.
Detailed Description
Adhesive strength test method: the hairless pigskin is cut into strips of 2.5cm x 5cm, the surface of the pigskin is sequentially wiped with isopropyl alcohol and water, the strips are dried to obtain the pigskin strips for testing, the adhesive materials in the following examples are coated on one ends of the two strips, the adhesive-coated parts are bonded together, and then the strips are placed in normal saline for 1 hour to enable the strips to be fully bonded together. The maximum adhesion was then determined by a tensile test, with a tensile rate of 5mm/min. The maximum adhesion was divided by the adhesion area to give the adhesion strength. Meanwhile, the bonded leather strips are placed in normal saline, antibacterial agents are added, and the leather strips are placed in a refrigerator at the temperature of 4 ℃ for soaking and storage for two weeks. The bond strength after soaking was then tested by the test method described above. The ratio of the adhesive strength after soaking to that before soaking is the water resistance of the adhesive.
Example 1
30g of polycaprolactone diol (Sigma-Aldrich, M) are weighed out n =500 g/mol) and 15g of methacryloyl chloride were dissolved in 200mL of dry dichloromethane, followed by dropwise addition of 12mL of triethylamine, and the reaction was carried out at room temperature for 24h. After the reaction was completed, the reaction solution was concentrated by rotary evaporation, and then the reaction solution was added dropwise to 500mL of anhydrous methanol. The lower precipitate was taken, redissolved with 50mL of dichloromethane, added dropwise again to 500mL of anhydrous methanol, and dried under vacuum to give polycaprolactone dimethacrylate.
9.964g of trimethylolpropane tris (3-mercaptopropionate) was dissolved in 300mL of tetrahydrofuran, followed by the addition of 19.2g of polycaprolactone dimethacrylate and 50mg of 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionne and reaction at room temperature under UV irradiation for 6 hours; then, 4.2g of maleic anhydride was added and the reaction was continued for 6 hours. The reaction solution was concentrated by distillation under reduced pressure, and then the product was redissolved with 40mL of tetrahydrofuran, followed by dropwise addition to 400mL of anhydrous methanol for precipitation. And taking the precipitate at the lower layer, repeating the dissolving-precipitating operation for 3 times, and vacuum drying to obtain the adhesive material.
Example 2
45g of polycaprolactone triol (Sigma-Aldrich, M) was weighed out n =900 g/mol), 15.18g of thioglycolic acid and 2.4g of 4-dimethylaminopyridine were dissolved in 300mL of dry dichloromethaneSubsequently, 100mL of a methylene chloride solution containing 34g of dicyclohexylcarbodiimide was added dropwise thereto, and the mixture was reacted at room temperature for 24 hours. After the reaction was completed, the reaction solution was concentrated by rotary evaporation, and then the reaction solution was added dropwise to 1000mL of anhydrous methanol. The lower precipitate was taken, redissolved with 50mL of dichloromethane, added dropwise again to 500mL of anhydrous methanol, and dried under vacuum to give polycaprolactone trithiol.
30g of polycaprolactone trithiol was dissolved in 500mL of tetrahydrofuran, followed by addition of 5.52g of 2- (acryloyloxy) ethyl methacrylate and 50mg of 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionate and reaction at room temperature under UV irradiation for 6h; then, 4.2g of maleic anhydride was added and the reaction was continued for 6 hours. The reaction solution was concentrated by distillation under reduced pressure, and then the product was redissolved with 40mL of tetrahydrofuran, followed by dropwise addition to 400mL of anhydrous methanol for precipitation. And taking the precipitate at the lower layer, repeating the dissolving-precipitating operation for 3 times, and vacuum drying to obtain the adhesive material.
Example 3
45g of polycaprolactone triol (Sigma-Aldrich, M) was weighed out n =900 g/mol), 17.3g of methacryloyl chloride was dissolved in 300mL of dry dichloromethane, followed by dropwise addition of 18mL of triethylamine, and the reaction was carried out at room temperature for 24h. After the reaction was completed, the reaction solution was concentrated by rotary evaporation, and then the reaction solution was added dropwise to 1000mL of anhydrous methanol. The lower precipitate was taken, redissolved with 50mL of dichloromethane, added dropwise again to 500mL of anhydrous methanol, and dried under vacuum to give polycaprolactone trimethacrylate.
3.53g of ethanedithiol was dissolved in 300mL of tetrahydrofuran, followed by addition of 21g of polycaprolactone trimethacrylate and 50mg of 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionate, and reaction was carried out at room temperature under UV irradiation for 6 hours; then, 1.467g of maleic anhydride was added, and the reaction was continued for 6 hours. The reaction solution was concentrated by distillation under reduced pressure, and then the product was redissolved with 40mL of tetrahydrofuran, followed by dropwise addition to 400mL of anhydrous methanol for precipitation. And taking the precipitate at the lower layer, repeating the dissolving-precipitating operation for 3 times, and vacuum drying to obtain the adhesive material.
Example 4
30g of poly (ethylene-propylene) is weighedCaprolactone diol (sigma-aldrich, M n =500 g/mol), 13.7g of thioglycolic acid and 1.8g of 4-dimethylaminopyridine were dissolved in 200mL of dried dichloromethane, followed by dropwise addition of 50mL of a dichloromethane solution containing 26g of dicyclohexylcarbodiimide, and reaction was carried out at room temperature for 24 hours. After the reaction was completed, the reaction solution was concentrated by rotary evaporation, and then the reaction solution was added dropwise to 1000mL of anhydrous methanol. The lower precipitate was taken, redissolved with 50mL of dichloromethane, added dropwise again to 500mL of anhydrous methanol, and dried under vacuum to give polycaprolactone dithiol.
19.5g of polycaprolactone dithiol was dissolved in 200mL of tetrahydrofuran, followed by addition of 4.72g of trimethylolpropane trimethacrylate and 50mg of 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionate, and reacted at room temperature under UV irradiation for 6 hours; then, 1.17g of maleic anhydride was added and the reaction was continued for 6 hours. The reaction solution was concentrated by distillation under reduced pressure, and then the product was redissolved with 50mL of tetrahydrofuran, followed by dropwise addition to 500mL of anhydrous methanol for precipitation. And taking the precipitate at the lower layer, repeating the dissolving-precipitating operation for 3 times, and vacuum drying to obtain the adhesive material.
Example 5
30g of the polycaprolactone trithiol prepared in example 2 was dissolved in 500mL of tetrahydrofuran, followed by the addition of 5.52g of 2- (acryloyloxy) ethyl methacrylate and 50mg of 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionne, and reacted for 6 hours at room temperature under UV irradiation; then, 8.4g of 4-bromomethylphenylboronic acid was added thereto, and the reaction was continued for 6 hours. The reaction solution was concentrated by distillation under reduced pressure, and then the product was redissolved with 40mL of tetrahydrofuran, followed by dropwise addition to 400mL of anhydrous methanol for precipitation. And taking the precipitate at the lower layer, repeating the dissolving-precipitating operation for 3 times, and vacuum drying to obtain the adhesive material.
Example 6
30g of the polycaprolactone trithiol prepared in example 2 was dissolved in 500mL of tetrahydrofuran, followed by the addition of 5.52g of 2- (acryloyloxy) ethyl methacrylate and 50mg of 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionne, and reacted for 6 hours at room temperature under UV irradiation; 16.8g of 3-acrylamido dopamine are then added and the reaction is continued for 6h. The reaction solution was concentrated by distillation under reduced pressure, and then the product was redissolved with 40mL of tetrahydrofuran, followed by dropwise addition to 400mL of anhydrous methanol for precipitation. And taking the precipitate at the lower layer, repeating the dissolving-precipitating operation for 3 times, and vacuum drying to obtain the adhesive material.
Comparative example 1
9.964g of trimethylolpropane tris (3-mercaptopropionate) was dissolved in 300mL of tetrahydrofuran, followed by addition of 22.4g of polycaprolactone dimethacrylate and 50mg of 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionne and reaction at room temperature under UV irradiation for 6 hours; then, 4.2g of maleic anhydride was added and the reaction was continued for 6 hours. The reaction solution was concentrated by distillation under reduced pressure, and then the product was redissolved with 40mL of tetrahydrofuran, followed by dropwise addition to 400mL of anhydrous methanol for precipitation. And taking the precipitate at the lower layer, repeating the dissolving-precipitating operation for 2 times, and vacuum drying to obtain the adhesive material.
Comparative example 2
9.964g of trimethylolpropane tris (3-mercaptopropionate) was dissolved in 300mL of tetrahydrofuran, followed by the addition of 19.2g of polycaprolactone dimethacrylate and 50mg of 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionne and the reaction at room temperature under UV irradiation for 6 hours. The reaction solution was concentrated by distillation under reduced pressure, and then the product was redissolved with 40mL of tetrahydrofuran, followed by dropwise addition to 400mL of anhydrous methanol for precipitation. And taking the precipitate at the lower layer, repeating the dissolving-precipitating operation for 3 times, and vacuum drying to obtain the adhesive material.
Comparative example 3
9.965g of trimethylolpropane tris (3-mercaptopropionate) was dissolved in 300mL of tetrahydrofuran, and then 14g of polyethylene glycol dimethacrylate (sigma-aldrich, m=700 g/mol) and 50mg of 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropionne were added and reacted at room temperature under ultraviolet irradiation for 6 hours; then, 3.5g of maleic anhydride was added and the reaction was continued for 6 hours. The reaction solution was distilled off under reduced pressure to dryness, and then the product was redissolved with 40mL of tetrahydrofuran, followed by dropwise addition to 400mL of anhydrous diethyl ether for precipitation. And taking the precipitate at the lower layer, repeating the dissolving-precipitating operation for 3 times, and vacuum drying to obtain the adhesive material.
The material properties of the examples and comparative examples are shown in Table 1.
Table 1 material properties of examples and comparative examples
Claims (10)
1. A medical adhesive comprising the reaction product of:
30-55 mole percent of polythiol functional group compound;
20-30 mole percent of compound with multiple carbon-carbon double bond functional groups;
20-45 mole percent of an adhesive compound;
0.001 to 0.05 mole percent of catalyst.
2. The medical adhesive according to claim 1, wherein the polythiol functional compound is a linear or multi-arm aliphatic polyester-based macromer having a thiol group as a terminal group, a combination of a saturated hydrocarbon chain having five to ten carbons and an ester bond as a repeating unit, and a molecular weight of 500 to 2000 g/mol.
3. The medical adhesive according to claim 1, wherein the compound having a multi-carbon double bond functional group is a linear or multi-arm aliphatic polyester-based macromer having a terminal carbon-carbon double bond group, a combination of saturated hydrocarbon chains having five to ten carbons and ester bonds as a repeating unit, and a molecular weight of 500 to 2000 g/mol.
4. The medical adhesive according to claim 2, wherein the compound having a multi-carbon double bond functional group is a small molecular monomer having more than two carbon-carbon double bonds per molecule and a molecular weight of less than 500 g/mol; preferably one or more of 3- (acryloyloxy) -2-hydroxypropyl methacrylate, 2- (acryloyloxy) ethyl methacrylate and trimethylolpropane trimethacrylate.
5. The medical adhesive according to claim 2 or 4, wherein the polythiol functional compound is a compound of formula I:
wherein m=5 to 10, n=5 to 30, and at least two R 3 A group.
6. The medical adhesive according to claim 3, wherein the polythiol functional group compound is a small molecular monomer having more than two thiol groups per molecule and a molecular weight of less than 500 g/mol; preferably one or more of ethanedithiol, ethylene glycol bis (3-mercaptopropionate), and trimethylolpropane tris (3-mercaptopropionate).
7. The medical adhesive according to claim 3 or 6, wherein the compound having a multi-carbon double bond functional group is a compound represented by formula II:
wherein x=5 to 10, y=5 to 30, and there are at least 2R 6 A group.
8. The medical adhesive according to any one of claims 1-7, wherein the adhesion compound is selected from one or more of maleic anhydride, 4-bromomethylphenylboronic acid, 3-acrylamido dopamine.
9. The medical adhesive according to any one of claims 1 to 8, wherein one of the materials of the polythiol functional group compound and the multi-carbon double bond functional group compound has a functionality of 2, the other material has a functionality of 3, and one material is a small molecular monomer and the other material is a large molecular monomer.
10. A method of preparing the medical adhesive of any one of claims 1-9, comprising the steps of:
(1) Dissolving a compound with a polythiol functional group in an organic solvent, adding a catalyst, adding a compound with a multi-carbon double bond functional group, and reacting for 3-24 hours;
(2) Adding an adhesive compound into the reaction solution obtained in the step (1) for reaction for 6-24 hours.
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CN118059326A (en) * | 2024-01-25 | 2024-05-24 | 明澈生物科技(苏州)有限公司 | Photo-curing material, ophthalmic drainage device and preparation method thereof |
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CN118059327A (en) * | 2024-01-25 | 2024-05-24 | 明澈生物科技(苏州)有限公司 | Photo-curing material, glaucoma drainage device and preparation method thereof |
CN118059326A (en) * | 2024-01-25 | 2024-05-24 | 明澈生物科技(苏州)有限公司 | Photo-curing material, ophthalmic drainage device and preparation method thereof |
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