CN105561377B - 一种可降解光固化医用粘合剂及其制备和应用 - Google Patents
一种可降解光固化医用粘合剂及其制备和应用 Download PDFInfo
- Publication number
- CN105561377B CN105561377B CN201510992697.XA CN201510992697A CN105561377B CN 105561377 B CN105561377 B CN 105561377B CN 201510992697 A CN201510992697 A CN 201510992697A CN 105561377 B CN105561377 B CN 105561377B
- Authority
- CN
- China
- Prior art keywords
- pgs
- medical
- adhesive
- preparation
- degradable
- 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.)
- Active
Links
- 230000001070 adhesive effect Effects 0.000 title claims abstract description 47
- 239000000853 adhesive Substances 0.000 title claims abstract description 42
- 238000000016 photochemical curing Methods 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000003756 stirring Methods 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
- 238000001035 drying Methods 0.000 claims abstract description 4
- CXMXRPHRNRROMY-UHFFFAOYSA-N n-Decanedioic acid Natural products OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 claims description 20
- 150000002148 esters Chemical class 0.000 claims description 13
- 229920000305 Nylon 6,10 Polymers 0.000 claims description 12
- 239000003999 initiator Substances 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 5
- 238000002844 melting Methods 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 4
- 235000011187 glycerol Nutrition 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229930006711 bornane-2,3-dione Natural products 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 230000008018 melting Effects 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 claims description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 2
- 125000002362 bornane-2,3-dione group Chemical group 0.000 claims description 2
- 238000004132 cross linking Methods 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 238000004062 sedimentation Methods 0.000 claims description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical group N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000004026 adhesive bonding Methods 0.000 abstract description 2
- OZJJSQVLXHKGHV-UHFFFAOYSA-N 2-isocyanoethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCC[N+]#[C-] OZJJSQVLXHKGHV-UHFFFAOYSA-N 0.000 abstract 2
- LKFHUFAEFBRVQX-UHFFFAOYSA-N decanedioic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.OC(=O)CCCCCCCCC(O)=O LKFHUFAEFBRVQX-UHFFFAOYSA-N 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 15
- 239000011521 glass Substances 0.000 description 12
- 238000007711 solidification Methods 0.000 description 12
- 230000008023 solidification Effects 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 238000000576 coating method Methods 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000009194 climbing Effects 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000004483 ATR-FTIR spectroscopy Methods 0.000 description 3
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000001723 curing Methods 0.000 description 3
- 230000009477 glass transition Effects 0.000 description 3
- -1 isobutyl AIBN Chemical compound 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 238000010008 shearing Methods 0.000 description 3
- 238000004513 sizing Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 244000061458 Solanum melongena Species 0.000 description 2
- 235000002597 Solanum melongena Nutrition 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000005357 flat glass Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- VNQXSTWCDUXYEZ-UHFFFAOYSA-N 1,7,7-trimethylbicyclo[2.2.1]heptane-2,3-dione Chemical compound C1CC2(C)C(=O)C(=O)C1C2(C)C VNQXSTWCDUXYEZ-UHFFFAOYSA-N 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920001651 Cyanoacrylate Polymers 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 108010080379 Fibrin Tissue Adhesive Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 244000283207 Indigofera tinctoria Species 0.000 description 1
- MWCLLHOVUTZFKS-UHFFFAOYSA-N Methyl cyanoacrylate Chemical compound COC(=O)C(=C)C#N MWCLLHOVUTZFKS-UHFFFAOYSA-N 0.000 description 1
- 241000233805 Phoenix Species 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 210000002403 aortic endothelial cell Anatomy 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- CSCPPACGZOOCGX-WFGJKAKNSA-N deuterated acetone Substances [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000005606 hygroscopic expansion Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000005395 methacrylic acid group Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005303 weighing Methods 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/12—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from polycarboxylic acids and polyhydroxy compounds
-
- 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
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/91—Polymers modified by chemical after-treatment
- C08G63/914—Polymers modified by chemical after-treatment derived from polycarboxylic acids and polyhydroxy compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Surgery (AREA)
- Materials For Medical Uses (AREA)
- Adhesives Or Adhesive Processes (AREA)
Abstract
本发明涉及一种可降解光固化医用粘合剂及其制备和应用,所述粘合剂为聚癸二酸甘油酯接枝甲基丙烯酸(2‑异氰基乙基)酯PGS‑IM;分子结构式为:将聚(癸二酸甘油酯)PGS中加入溶剂,氮气保护下,置于油浴中搅拌至PGS溶解,然后加入甲基丙烯酸(2‑异氰基乙基)酯,反应15‑120min,提纯后干燥即得。本发明PGS‑IM常温下为粘稠的半固体,施胶方便,可蓝光或者紫外固化,对组织无损伤,固化迅速,固化后粘结性能良好。
Description
技术领域
本发明属于粘合剂及其制备领域,特别涉及一种可降解光固化医用粘合剂及其和应用。
背景技术
缝合技术是外科手术成功的关键,具有相当的技术难度,且耗时较长,技术均一性差。对于外科手术缝合而言,如果缝合不严密,可能会引起局部组织出血、感染甚至不愈合。医用粘合剂做为一种新的闭合技术,具有简便易用,操作快捷,同时可具有止血功能等优点,因而受到人们越来越广泛的关注。当前临床上可用的粘合剂主要包括医用级氰基丙烯酸酯(CA)和纤维蛋白封闭剂,前者体内使用有一定的毒性,后者粘结性弱易被冲洗掉,因而它们的应用都受到限制。近年来,新型医用粘合剂的研究越来越多,开发出如改性聚(乙烯醇)粘合剂[3],多糖类生物粘合剂,胶原类粘合剂等。这些粘合剂往往是通过化学反应实现粘结组织的,一般要么涂上后固化快,不便于实现细微的调整,要么固化慢,粘结作用较弱。光固化医用粘合剂由于其施胶方便,固化速度快,粘结强度高,越来越受到研究者青睐。然而,这些粘合剂多是亲水性的,在体内易吸水膨胀或者被冲水快速冲走。另外,当前光固化医用粘合剂的研究多集中于紫外光固化方面,由于紫外光对组织和细胞有一定损伤,故而使其应用受到限制。
发明内容
本发明所要解决的技术问题是提供一种可降解光固化医用粘合剂及其制备和应用,本发明的粘合剂制备工艺简单,材料易得,成本低,所得粘合剂具有较好的粘结性能和较高的粘结强度,同时具有良好的生物相容性,可用于医用粘合剂。
本发明的一种可降解光固化医用粘合剂,所述粘合剂为聚癸二酸甘油酯接枝甲基丙烯酸(2-异氰基乙基)酯PGS-IM;
分子结构式为:其中x:y为0.01-100:1,R为氢原子或PGS链段。
本发明的一种可降解光固化医用粘合剂的制备方法,包括:
(1)将摩尔比为1:1的癸二酸、甘油,混合,熔融,通N2搅拌,然后抽真空,降至室温,得到聚(癸二酸甘油酯)PGS;
(2)将上述聚(癸二酸甘油酯)PGS中加入溶剂,氮气保护下,置于油浴中搅拌至PGS溶解,然后加入甲基丙烯酸(2-异氰基乙基)酯,反应15-120min,分离提纯,即得。
所述步骤(1)中熔融温度为125-138℃。
所述步骤(1)中搅拌时间为18-24h。
所述步骤(1)中抽真空为125-138℃下抽真空(真空度为4-8mbar)36-48h。
步骤(2)中加料均在手套箱中进行,其中手套箱中水含量≤0.1ppm,氧含量≤0.1ppm。
所述步骤(2)中溶剂为无水二甲基甲酰胺DMF。
所述步骤(2)中聚(癸二酸甘油酯)PGS、甲基丙烯酸(2-异氰基乙基)酯的摩尔比例关系为:0.01:1-100:1。
所述步骤(2)中油浴温度为60-95℃。
所述步骤(2)中提纯方法为用水沉淀1-5次。
所述步骤(2)中干燥方法为在-20-0℃冷冻1-12h,在压强1-500Pa下冷冻干燥6-48h。
本发明的一种可降解光固化医用粘合剂的应用,包括:
将PGS-IM施于拟粘接的物件表面,将物件接合在一起,然后置于蓝光或紫外光下固化5s-5min。
所述蓝光固化为加蓝光引发剂后固化,紫外光固化为加紫外光引发剂后固化;其中蓝光引发剂为樟脑醌;紫外光引发剂为Igra2959。
本发明的一种可降解光固化医用粘合剂的应用,PGS-IM进行热交联施胶,具体为:将PGS-IM和自由基引发剂施于拟粘接的物件表面,将物件接合在一起,然后40-100℃加热,其中自由基引发剂为偶氮二异丁AIBN和/或过氧化二苯甲酰BPO。
本发明的PGS-IM由以下方法进行表征,测试:
PGS-IM的结构表征:
PGS-IM的结构由核磁共振氢谱(1H NMR)和傅里叶变换衰减全反射红外光谱(ATR-FTIR)进行确定。1H NMR谱图由Bruke AM-400(400MHz)型核磁共振仪,氘代丙酮作溶剂测定。ATR-FTIR测试由红外光谱测定仪(Nicolet 6700)完成。
PGS-IM的热学性能表征:
PGS-IM的热学性能通过美国TA公司的Discovery型热失重分析仪(TGA)和耐驰公司的204 F1 Phoenix型差示扫描量热仪(DSC)测试所得。TGA测试在氮气氛围下,以10℃/min的升温速率从40℃升到500℃。DSC测试是在氮气氛围下,10℃/min的速率从室温升温到150℃消除热历史,然后降至-50℃,再从-50℃升温到150℃测试所得。玻璃化转变温度(Tg)按玻璃化转变过程中的中点温度确定,由仪器自带的分析软件得出。
PGS-IM粘结性能实验:
PGS-IM的粘结实验由透光性较好的玻璃板和可作心脏补片的材料聚(对苯二甲酸乙二醇酯)(PET)板材完成,光源为一台蓝光光固化机(波长:430-485nm,1500Mw/cm2),参考国标(GB/T 7124-2008)中胶黏剂的测试方法。将蓝光光固化催化剂樟脑醌(百灵威,98%)和2.4-二甲氨基-苯甲酸乙酯(百灵威,98%)按1:4(m:m)混合后,按1%(w/w)当量加入PGS-IM中,混合均匀,避光存放。一端带孔(便于力学测试)的玻璃板(100mm×35mm×5mm)另一端均匀涂上20mg混有催化剂的PGS-IM,涂胶面积35mm×12mm,将另一块玻璃板压紧固定,用蓝光光固化机照射60s。用铁丝穿过玻璃板的孔,将铁丝固定在万能试验机(长春科新试验仪器有限公司)夹具上,以5mm/min拉伸速度进行拉伸测试。PET板测试采用8mm厚的PET板,将其裁剪成100mm×20mm的长条,每两片PET板间均匀涂上10mg混有催化剂的PGS-IM,涂胶面积20mm×10mm,固定后,蓝光光固化机照射60s。将PET板样条直接夹在万能试验机(长春科新试验仪器有限公司,配备200N传感器)夹具上以5mm/min速度进行拉伸测试。玻璃和PET板均测试5个样品,剪切强度取平均值。PGS-IM的生物相容性测试:
将混有催化剂的PGS-IM配置成1g/L的四氢呋喃(THF)溶液,取100μl均匀涂在细胞爬片()上,待溶剂挥发后,蓝光光固化机照射30秒,固化后用蒸馏水水冲洗掉残余溶剂。将含有新合成的生物胶涂层的玻璃片和对照的纯玻璃片各三块,放在含有DMEM(11965-092,Gibco公司,美国)的6孔平底板中,然后,将按参考文献中[18,19]中描述的方法培养的RAECs重新悬浮在上述6孔细胞培养板中培养。培养后第二天用倒置相差显微镜(Olympus,日本)200倍光镜观察细胞生长情况。
本发明粘合剂的制备方程:
其中x:y=0.01-100:1。
有益效果
(1)本发明的粘合剂制备工艺简单,材料易得,成本低,所得粘合剂具有较好的粘结性能和较高的粘结强度,同时具有良好的生物相容性,可用于医用粘合剂;
(2)本发明PGS-IM常温下为粘稠的半固体,施胶方便,可蓝光或者紫外固化,对组织无损伤,固化迅速,固化后粘结性能良好。
附图说明
图1为PGS-IM的1H NMR谱图;
图2为PGS-IM的红外光谱谱图;
图3为PGS-IM的热学曲线:(A)TGA曲线,(B)DSC曲线;
图4为蓝光固化的PGS-IM的粘接性能,(A)粘接玻璃的抗剪切拉伸力学曲线,(B)粘接PET板的抗剪切拉伸力学曲线;
图5为大鼠胸主动脉内皮细胞(RAECs)培养两天后的倒置相差显微镜图像;(A)普通玻片细胞爬片的对照组,(B)涂有蓝光固化PGS-IM涂层的细胞爬片;图中央弧形部分是圆形细胞爬片与培养皿结合部,放大200倍,scale bars=500μm。
具体实施方式
下面结合具体实施例,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。此外应理解,在阅读了本发明讲授的内容之后,本领域技术人员可以对本发明作各种改动或修改,这些等价形式同样落于本申请所附权利要求书所限定的范围。
实施例1
PGS的制备:重结晶纯化后的癸二酸20.2574g(0.1mol)和甘油9.2037g(0.1mol)加入三口烧瓶中,135℃下熔融,通N2搅拌24h,然后135℃下抽真空(4mbar)48h,降至室温得到淡黄色蜡状固体。
1H NMR(400MHz,Chloroform-d)δ3.45-5.29(m,5H),2.35(m,4H),1.62(m,4H),1.35(m,4H)。
PGS-IM的合成:反应的加料在手套箱中(水含量≤0.1ppm,氧含量≤0.1ppm)进行,称量1210.0mg(4.69mmol)PGS加入25ml茄型反应瓶中,再加入1.6ml无水DMF,氮气保护下,置于80℃油浴中搅拌至PGS完全溶解。加入359.5mg(2.35mmol)甲基丙烯酸(2-异氰基乙基)酯,20分钟后反应结束。用去离子水沉淀除去DMF,再用四氢呋喃溶解,去离子水沉淀三次,除去未反应的甲基丙烯酸(2-异氰基乙基)酯单体,得到白色色粘稠状的半固体(1038.0mg)产率70%。
从PGS-IM的1H NMR谱图(图1)可以清楚的看到PGS的癸二酸部分的质子信号分别标为‘a1’,‘a2’,‘a3’(δ=1.35、1.62和2.35ppm),且积分比为2:1:1,证实了癸二酸部分的结构。标有‘b’(δ=1.93ppm)的信号是甲基丙烯酸(2-异氰基乙基)酯中甲基的质子信号,标有‘c1’(δ=5.61ppm)和‘c2’(δ=6.12ppm)的信号对应甲基丙烯酸(2-异氰基乙基)酯双键中质子的信号,三者积分比为3:1:1,与结构完全符合,从而证实了甲基丙烯酸(2-异氰基乙基)酯的成功接枝。根据接枝侧基的特征峰‘c1’(1个烯氢)和主链的特征峰‘a2’(癸二酸结构中的4个亚甲基氢)的积分比为0.08:1,可以计算出接枝率为32%。
PGS-IM的热学性能表征
PGS-IM的热学性能通过热失重分析(TGA)和差示扫描量热(DSC)进行分析(图3)。从TGA(图3A)分析中可以看出PGS-IM在200℃内无重量减少,说明它具有比较广的温度使用范围。从DSC(图3B)分析中可以得出PGS-IM的玻璃化转变温度(Tg)为-30.6℃。在测试温度范围(-50℃到150℃)内没有观察其熔融和结晶峰,说明在其使用的体温附近,PGS-IM为玻璃化温度之上的无定型状态,具有一定的流动性,便于其涂覆在待粘接底物的表面。
PGS-IM粘结性能表征
选用了玻璃板和PET板(常用的心脏补片材料)作为被粘接材料对PGS-IM的粘结性能进行了测试。首先用PGS-IM将两块测试的板材初步粘接到一起,然后用对组织基本无损伤的蓝光对其进行原位即时固化。固化30秒后,即达到较好的粘接性,两块被粘接的板材作为整体可以任意移动,不发生相对移位。而后对其抗剪切拉伸情况进行量化的测试。结果如图4所示,其中图4A图4B分别为粘接玻璃和PET板的测试结果。结果显示蓝光固化的PGS-IM粘合剂对二者均有较好的粘接性,对玻璃和PET板的粘结强度分别达到为0.84±0.12MPa和0.39±0.07MPa。
PGS-IM的生物相容性测试
分别在普通玻片和含有蓝光固化后的PGS-IM涂层的细胞爬片上培养RAECs。培养两天后,用倒置相差显微镜(Olympus,日本)观察两组细胞的生长情况(图5)。从图中可以看出大鼠主动脉内皮细胞在蓝光固化的PGS-IM胶层上生长良好,在涂层及其放置的细胞培养皿上看不出明显的差异(图5B)。总体生长情况和无涂层的对照组(图5A)相当。说明PGS-IM具有良好的细胞相容性。
实施例2
PGS的制备:重结晶纯化后的癸二酸20.2574g(0.1mol)和甘油9.2037g(0.1mol)加入三口烧瓶中,135℃下熔融,通N2搅拌24h,然后135℃下抽真空(4mbar)48h,降至室温得到淡黄色蜡状固体。
PGS-IM的合成:反应的加料在手套箱中(水含量≤0.1ppm,氧含量≤0.1ppm)进行,称量4.69mmol)PGS加入25ml茄型反应瓶中,再加入1.6ml无水DMF,氮气保护下,置于80℃油浴中搅拌至PGS完全溶解。加入4mmol甲基丙烯酸(2-异氰基乙基)酯,20分钟后反应结束。用去离子水沉淀除去DMF,再用四氢呋喃溶解,去离子水沉淀三次,除去未反应的甲基丙烯酸(2-异氰基乙基)酯单体,得到白色色粘稠状的半固体,产率75%。
选用了玻璃板和PET板(常用的心脏补片材料)作为被粘接材料对PGS-IM的粘结性能进行了测试,进行紫外光固化。结果显示紫外光固化的PGS-IM粘合剂对二者均有较好的粘接性。
Claims (10)
1.一种可降解光固化医用粘合剂,其特征在于:所述粘合剂为聚癸二酸甘油酯接枝甲基丙烯酸(2-异氰基乙基)酯PGS-IM;分子结构式为:
其中x:y为0.01-100:1,R为氢原子或癸二酸链段。
2.一种如权利要求1所述的可降解光固化医用粘合剂的制备方法,包括:
(1)将摩尔比为1:1的癸二酸、甘油,混合,熔融,通N2搅拌,然后抽真空,降至室温,得到聚(癸二酸甘油酯)PGS;
(2)在上述聚(癸二酸甘油酯)PGS中加入溶剂,氮气保护下,置于油浴中搅拌至PGS溶解,然后加入甲基丙烯酸(2-异氰基乙基)酯,反应15-120min,提纯后干燥即得;其中聚(癸二酸甘油酯)PGS、甲基丙烯酸(2-异氰基乙基)酯的摩尔量比例关系为:0.01:1-100:1。
3.根据权利要求2所述的一种可降解光固化医用粘合剂的制备方法,其特征在于:所述步骤(1)中熔融温度为125-138℃;搅拌时间为18-24h;抽真空为125-138℃下抽真空36-48h,真空度为4-8mbar。
4.根据权利要求2所述的一种可降解光固化医用粘合剂的制备方法,其特征在于:步骤(2)中加料均在水含量≤0.1ppm,氧含量≤0.1ppm下进行。
5.根据权利要求2所述的一种可降解光固化医用粘合剂的制备方法,其特征在于:所述步骤(2)中溶剂为无水二甲基甲酰胺。
6.根据权利要求2所述的一种可降解光固化医用粘合剂的制备方法,其特征在于:所述步骤(2)中油浴温度为60-95℃。
7.根据权利要求2所述的一种可降解光固化医用粘合剂的制备方法,其特征在于:所述步骤(2)中提纯方法为用水沉淀1-5次;干燥方法为在-20-0℃冷冻1-12h,在压强1-500Pa下冷冻干燥6-48h。
8.一种如权利要求1所述的可降解光固化医用粘合剂的应用,包括:
将PGS-IM施于拟粘接的物件表面,将物件接合在一起,然后置于蓝光或紫外光下固化5s-5min。
9.根据权利要求8所述的一种可降解光固化医用粘合剂的应用,其特征在于:蓝光固化为加蓝光引发剂后固化,紫外光固化为加紫外光引发剂后固化;其中蓝光引发剂为樟脑醌体系;紫外光引发剂为Igra2959。
10.一种如权利要求1所述的可降解光固化医用粘合剂的应用,其特征在于:PGS-IM进行热交联施胶,具体为:将PGS-IM和自由基引发剂施于拟粘接的物件表面,将物件接合在一起,然后40-100℃加热,其中自由基引发剂为偶氮二异丁腈AIBN和/或过氧化二苯甲酰BPO。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510992697.XA CN105561377B (zh) | 2015-12-25 | 2015-12-25 | 一种可降解光固化医用粘合剂及其制备和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510992697.XA CN105561377B (zh) | 2015-12-25 | 2015-12-25 | 一种可降解光固化医用粘合剂及其制备和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105561377A CN105561377A (zh) | 2016-05-11 |
CN105561377B true CN105561377B (zh) | 2018-09-25 |
Family
ID=55872369
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510992697.XA Active CN105561377B (zh) | 2015-12-25 | 2015-12-25 | 一种可降解光固化医用粘合剂及其制备和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105561377B (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106620827B (zh) * | 2017-01-25 | 2019-12-31 | 东华大学 | 一种聚(癸二酸甘油二酯)的应用 |
CN111956818B (zh) * | 2020-08-17 | 2022-02-08 | 江南大学 | 一种易拉罐拉环处的蓝光消毒洁净方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007082304A2 (en) * | 2006-01-12 | 2007-07-19 | Massachusetts Institute Of Technology | Biodegradable elastomers |
WO2011091411A2 (en) * | 2010-01-25 | 2011-07-28 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Polyesters, methods of making polyesters and uses therefor |
CN103937419A (zh) * | 2013-01-22 | 2014-07-23 | 香港纺织及成衣研发中心有限公司 | 一种具有微纳图案表面结构的粘弹胶带 |
-
2015
- 2015-12-25 CN CN201510992697.XA patent/CN105561377B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007082304A2 (en) * | 2006-01-12 | 2007-07-19 | Massachusetts Institute Of Technology | Biodegradable elastomers |
WO2011091411A2 (en) * | 2010-01-25 | 2011-07-28 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Polyesters, methods of making polyesters and uses therefor |
CN103937419A (zh) * | 2013-01-22 | 2014-07-23 | 香港纺织及成衣研发中心有限公司 | 一种具有微纳图案表面结构的粘弹胶带 |
Non-Patent Citations (2)
Title |
---|
Poly(glycerol sebacate) biomaterial:synthesis and biomedical applications;Xian Jun Loh et al.;《Journal of Materials Chemistry B》;20151021;第3卷(第39期);7633-7804 * |
Synthesis and Characterization of Photocurable Elastomers from Poly(glycerol-co-sebacate);Christiaan L.E. Nijst et al.;《Biomacromolecules》;20070829;第8卷(第10期);3067-3073 * |
Also Published As
Publication number | Publication date |
---|---|
CN105561377A (zh) | 2016-05-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8759465B2 (en) | Cross-linkable polymeric compositions | |
Mehdizadeh et al. | Injectable citrate-based mussel-inspired tissue bioadhesives with high wet strength for sutureless wound closure | |
CN108929412A (zh) | 一种温度响应的粘附性可注射水凝胶的制备方法 | |
WO2007127225A2 (en) | Cross-linkable polymeric compositions | |
CN113292671B (zh) | 一种含有苯硼酸基团的高分子交联剂、其制备的生物粘合剂及制备方法和应用 | |
EP2292277A2 (en) | Polymer coated sutures | |
US20110015759A1 (en) | Adhering composition and method of applying the same | |
CN105925220A (zh) | 一种对皮肤粘性优良的医用压敏胶及其制备方法和应用 | |
CN105561377B (zh) | 一种可降解光固化医用粘合剂及其制备和应用 | |
US20180169295A1 (en) | Film, manufacturing method thereof, and use thereof | |
Gong et al. | Photopolymerizable and moisture-curable polyurethanes for dental adhesive applications to increase restoration durability | |
Higashi et al. | Thermo-responsive polymer brushes on glass plate prepared from a new class of amino acid-derived vinyl monomers and their applications in cell-sheet engineering | |
Chen et al. | A supramolecular copolymer based on small molecules, used for a multifunctional adhesive and rapid hemostasis | |
Cui et al. | Strain hardening and highly resilient hydrogels crosslinked by chain-extended reactive pseudo-polyrotaxane | |
Zhang et al. | A nucleobase-inspired super adhesive hydrogel with desirable mechanical, tough and fatigue resistant properties based on cytosine and ε-caprolactone | |
CN114716626A (zh) | 一种用于硬膜修复的湿性粘合水凝胶及其制备方法和应用 | |
CN113999135A (zh) | 粘附分子以及含粘附分子的仿生型水凝胶 | |
CN116693931B (zh) | 一种超结构多孔湿性粘合水凝胶及其制备方法与应用 | |
CN111053946B (zh) | 一种基于多糖和超支化多肽的双组分组织粘合剂及其制备方法 | |
JP6096887B2 (ja) | シアノアクリレートモノマーを含む硬化性組成物 | |
CN115746388B (zh) | 一种含多尺度孔道网络的自粘附型止血修复凝胶、其制备方法及应用 | |
CN109880132B (zh) | 六臂聚乙二醇氨基水凝胶、其制备方法及应用 | |
Kowalczuk et al. | Self‐Degrading Multifunctional PEG‐Based Hydrogels—Tailormade Substrates for Cell Culture | |
Tanaka et al. | Polymeric arsenicals as scaffolds for functional and responsive hydrogels | |
CN108623729A (zh) | 基于超支化聚合物的水凝胶及其应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |