CN106565922B - 一种在生理环境中膨胀率极低的高分子水凝胶及制备和应用 - Google Patents
一种在生理环境中膨胀率极低的高分子水凝胶及制备和应用 Download PDFInfo
- Publication number
- CN106565922B CN106565922B CN201610937144.9A CN201610937144A CN106565922B CN 106565922 B CN106565922 B CN 106565922B CN 201610937144 A CN201610937144 A CN 201610937144A CN 106565922 B CN106565922 B CN 106565922B
- Authority
- CN
- China
- Prior art keywords
- hydrogel
- peg
- expansion rate
- extremely low
- pegda
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F299/00—Macromolecular compounds obtained by interreacting polymers involving only carbon-to-carbon unsaturated bond reactions, in the absence of non-macromolecular monomers
- C08F299/02—Macromolecular compounds obtained by interreacting polymers involving only carbon-to-carbon unsaturated bond reactions, in the absence of non-macromolecular monomers from unsaturated polycondensates
- C08F299/026—Macromolecular compounds obtained by interreacting polymers involving only carbon-to-carbon unsaturated bond reactions, in the absence of non-macromolecular monomers from unsaturated polycondensates from the reaction products of polyepoxides and unsaturated monocarboxylic acids, their anhydrides, halogenides or esters with low molecular weight
- C08F299/028—Macromolecular compounds obtained by interreacting polymers involving only carbon-to-carbon unsaturated bond reactions, in the absence of non-macromolecular monomers from unsaturated polycondensates from the reaction products of polyepoxides and unsaturated monocarboxylic acids, their anhydrides, halogenides or esters with low molecular weight photopolymerisable compositions
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
-
- 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
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/331—Polymers modified by chemical after-treatment with organic compounds containing oxygen
- C08G65/332—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof
- C08G65/3322—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof acyclic
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
- C08J7/02—Chemical treatment or coating of shaped articles made of macromolecular substances with solvents, e.g. swelling agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0068—General culture methods using substrates
- C12N5/0075—General culture methods using substrates using microcarriers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2355/00—Characterised by the use of homopolymers or copolymers, obtained by polymerisation reactions only involving carbon-to-carbon unsaturated bonds, not provided for in groups C08J2323/00 - C08J2353/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2531/00—Microcarriers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/30—Synthetic polymers
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Animal Behavior & Ethology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Public Health (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Dispersion Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Macromonomer-Based Addition Polymer (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及一种在生理环境中膨胀率极低的高分子水凝胶及其制备和应用,包括PEGDA的合成和膨胀率极低的PEG水凝胶的制备。该方法以不同分子量的聚乙二醇(PEG)为原料,通过酯化反应合成不同分子量的两端带有丙烯酰基的聚乙二醇二丙烯酸酯(PEGDA);然后将中间产物PEGDA以不同的浓度进行聚合得到化学交联的PEG水凝胶;最后通过膨胀率的测量筛选出符合要求的低膨胀率的PEG水凝胶。该材料具有生物相容性好、理化性质稳定、膨胀率极低等特点。所得的产物能同时满足基础研究以及临床应用的需求。
Description
技术领域
本发明涉及一种在生理环境中膨胀率极低的水凝胶及制备和应用,具体涉及一种以聚乙二醇为本体,在其两端连接上丙烯酰基,并以一定浓度进行聚合后得到膨胀率很低的聚乙二醇水凝胶的制备技术。本发明属于生物医用高分子材料领域。
背景技术
水凝胶是一类在水中会发生溶胀但不溶解的三维交联网络结构。由于其良好的生物相容性、多孔性和类似于体内组织的粘弹性,高分子水凝胶已成为再生医学研究中一颗冉冉升起的新星,尤其是在组织工程中被广泛用作人工基质材料(Adv. Mater., 2009,21: 3307)。水凝胶可以由多种成分通过不同的合成方法制备得到,生物医用的水凝胶材料包括以聚乙二醇为主的抗细胞黏附材料(Biomaterials, 2011, 32: 4725)以及由细胞外基质组分合成的利于细胞黏附的材料,如透明质酸水凝胶(Adv. Mater., 2011, 23:H41)、海藻酸盐水凝胶(Nat. Mater., 2010, 9: 518)、胶原水凝胶(Biomaterials, 2010,31: 1875)和纤维蛋白水凝胶(Nat. Mater., 2012, 11: 734)等。它们被广泛应用于组织工程支架材料,同时在药物和蛋白质的可控传递以及细胞与生物材料间相互作用的研究等方面也发挥着不可替代的作用。
作为一种高分子网络结构,水凝胶会大量吸水溶胀,直至其网络空腔达到一种饱和状态。由于细胞的体外培养介质以及生物体内的细胞外基质都是液体环境,因此水凝胶的溶胀性能会对细胞实验、动物实验乃至临床治疗的成败产生重要的影响。水凝胶的膨胀率是指在液体环境中达到溶胀平衡后的水凝胶相对于溶胀之前的干态,其质量、体积等参数的比值,它反映了材料内部结构的致密程度。影响水凝胶膨胀率的因素众多,而要实现其膨胀率的可控调节相当复杂,需要深厚的高分子理论基础以及反复的实验尝试。
尽管水凝胶作为一种生物材料有其独特的优势,但传统水凝胶由于在生理条件下会不可避免地发生溶胀而导致其生物医学方面的应用受到一定的限制(Science, 2014,343: 873)。一旦水凝胶发生了较大幅度的溶胀,其表面及内部的一些理化性质往往也会随之发生不可控的变化,这势必会对其应用产生一定的负面影响。因此,以现有生物材料为基础,经过一定的修饰和改进,得到膨胀率很低甚至基本不溶胀的水凝胶材料,从而在后续研究中尽可能地保持其原有的各种性质,是当前相关领域的一个迫在眉睫的研究任务。在这其中,聚乙二醇基水凝胶材料既可以作为抗细胞黏附和组织粘连的材料,又能够通过物理或化学手段修饰上特定的细胞外基质蛋白并进一步作为支架、囊泡等细胞载体。因此,制备出膨胀率极低的聚乙二醇水凝胶,对于细胞生物学和临床医学的研究都有着极其重要的意义。
发明内容
本发明目的在于针对传统水凝胶具有较大的膨胀率而导致其生物医学应用受到制约的不足,提供一种在生理条件下具有极低膨胀率的聚乙二醇水凝胶材料的制备方法。该方法以不同分子量的聚乙二醇(PEG)为原料,通过酯化反应合成不同分子量的两端带有丙烯酰基的聚乙二醇二丙烯酸酯(PEGDA);然后将中间产物PEGDA以不同的浓度进行聚合得到化学交联的PEG水凝胶;最后通过膨胀率的测量筛选出符合要求的低膨胀率的PEG水凝胶。PEG的分子量越大,则水凝胶网络结构的节点间距越大,空腔越大,因此,为了得到低膨胀率的水凝胶,就需要PEGDA水溶液的浓度越低,这样方可利用大量的水占据空腔,从而降低水凝胶的膨胀率。该材料具有生物相容性好、理化性质稳定、膨胀率极低等特点。所得的产物能同时满足基础研究以及临床应用的需求。
为实现上述目的,本发明的具体技术方案如下:
一种在生理环境中膨胀率极低的高分子水凝胶的制备方法,其特征在于,包括以下步骤:
(1) PEGDA的合成
首先将一些实验原料进行纯化,二氯甲烷(DCM)用五氧化二磷进行加热回流除水;三乙胺(TEA)用分子筛干燥后蒸馏提纯;丙烯酰氯蒸馏提纯;PEG用共沸法进行除水;
将一定量的PEG溶解于100 mL甲苯中,加入少量沸石以防止暴沸,加热至一定温度,利用共沸法在蒸馏出甲苯的同时带走PEG中的水分,待剩下20 mL甲苯时,停止加热,并冷却至室温,加入120 mL DCM以溶解析出的PEG,在冰浴条件下加入一定量的TEA,TEA与PEG的摩尔比为3:1 ~ 10:1,将一定量的丙烯酰氯用20 mL DCM进行稀释并充分混匀,然后利用滴液漏斗逐滴滴加至PEG溶液中,滴加全程需在冰浴以及剧烈搅拌下进行;丙烯酰氯与PEG的摩尔比为3:1 ~ 10:1,控制滴加速度,使滴加全程耗时2~4 h,丙烯酰氯滴加完毕后,可撤去冰浴,室温下反应12~24 h;
反应结束后,将反应产物进行抽滤以除去不溶性杂质,然后利用硅藻土柱层析法吸附副产物三乙胺盐酸盐,利用旋蒸对溶液进行浓缩,然后在剧烈搅拌下将浓缩液缓缓加入1000 mL无水乙醚中,于-20℃静置沉降24 h,沉降完毕后,弃去上层清液,对下层沉淀进行抽滤,收集滤渣,真空干燥48 h以上,得中间产物PEGDA大单体;
(2) 膨胀率极低的PEG水凝胶的制备
将中间产物PEGDA溶解于超纯水中,配制成一定浓度的水溶液,然后加入光引发剂D2959,避光搅拌10 min,抽真空以除去溶液中的氧气,D2959的用量为PEGDA的0.05%,重量比,将溶液滴加在样品槽中,通入氮气,在波长365 nm、功率15 W的紫外灯下聚合1~3 h,聚合结束后,用刀片将产物从样品槽中分离出来,得到PEG水凝胶;
将水凝胶置于PBS中浸泡,在37℃下溶胀48 h,以溶胀后的直径与溶胀前的直径的比值记为水凝胶的膨胀率,筛选出其中膨胀率低于1.10的各种水凝胶。
所述的PEG的数均分子量可以为2000、4000、6000、8000、10000、20000、35000中的一种。
所述的TEA与PEG的摩尔比为3:1 ~ 10:1。
所述的丙烯酰氯与PEG的摩尔比为3:1 ~ 10:1。
所述的PEGDA水溶液的浓度为3~30 %,重量分数。
一种在生理环境中膨胀率极低的高分子水凝胶,其特征在于,根据上述任一所述方法制备得到。
一种在生理环境中膨胀率极低的高分子水凝胶在生物医学的应用。
该材料具有生物相容性好、理化性质稳定、膨胀率极低等特点。所得的产物能同时满足基础研究以及临床应用的需求。
本发明的优点在于:
(1) 本发明以聚乙二醇为基本原料,通过酯化反应合成两端带有双键的大单体,然后利用化学交联制备出在生理条件下膨胀率极低的PEG水凝胶。所用原料生物安全性高,部分已是商业化产品。
(2) 本发明制备的聚乙二醇水凝胶具有良好的理化稳定性、生物相容性和低膨胀率。
(3) 本发明制备的聚乙二醇水凝胶容易实现多种修饰,能够便于进行体外细胞实验以及体内植入研究,而且由于其膨胀率极低,在后续操作时基本不会发生性质改变。
(4) 本发明中的制备方法工艺简单,可操作性强,能进一步满足生产和应用。
具体实施方式
以下通过具体的实施例对本发明的技术方案作进一步描述。以下的实施例是对本发明的进一步说明,而不限制本发明的范围。
实施例1
首先将一些实验原料进行纯化。二氯甲烷(DCM)用五氧化二磷进行加热回流除水;三乙胺(TEA)用分子筛干燥后蒸馏提纯;丙烯酰氯蒸馏提纯;PEG用共沸法进行除水。
将10 mmol PEG (M n 2000)溶解于100 mL甲苯中,加入少量沸石以防止暴沸,加热至一定温度,利用共沸法在蒸馏出甲苯的同时带走PEG中的水分。待剩下约20 mL甲苯时,停止加热,并冷却至室温。加入120 mL DCM以溶解析出的PEG。在冰浴条件下加入30 mmolTEA。将30 mmol丙烯酰氯用20 mL DCM进行稀释并充分混匀,然后利用滴液漏斗逐滴滴加至PEG溶液中,滴加全程需在冰浴以及剧烈搅拌下进行。控制滴加速度,使滴加全程耗时2 h。丙烯酰氯滴加完毕后,可撤去冰浴,室温下反应12 h。
反应结束后,将反应产物进行抽滤以除去不溶性杂质,然后利用硅藻土柱层析法吸附副产物三乙胺盐酸盐。利用旋蒸对溶液进行浓缩,然后在剧烈搅拌下将浓缩液缓缓加入1000 mL无水乙醚中,于-20℃静置沉降24 h。沉降完毕后,弃去上层清液,对下层沉淀进行抽滤。收集滤渣,真空干燥48 h以上,得中间产物PEGDA大单体(M n 2000)。
将3 g中间产物PEGDA溶解于7 g超纯水中,配制成重量分数为30%的水溶液,然后加入光引发剂0.0015 g D2959,避光搅拌10 min,抽真空以除去溶液中的氧气。将溶液滴加在样品槽中,通入氮气,在波长365 nm、功率15 W的紫外灯下聚合1 h。聚合结束后,用刀片将产物从样品槽中分离出来,得到PEG水凝胶。
将水凝胶置于PBS中浸泡,在37 °C下溶胀48 h,测定出水凝胶的膨胀率约为1.06。
实施例2
首先将一些实验原料进行纯化。二氯甲烷(DCM)用五氧化二磷进行加热回流除水;三乙胺(TEA)用分子筛干燥后蒸馏提纯;丙烯酰氯蒸馏提纯;PEG用共沸法进行除水。
将2.5 mmol PEG (M n 8000)溶解于100 mL甲苯中,加入少量沸石以防止暴沸,加热至一定温度,利用共沸法在蒸馏出甲苯的同时带走PEG中的水分。待剩下约20 mL甲苯时,停止加热,并冷却至室温。加入120 mL DCM以溶解析出的PEG。在冰浴条件下加入20 mmolTEA。将20 mmol丙烯酰氯用20 mL DCM进行稀释并充分混匀,然后利用滴液漏斗逐滴滴加至PEG溶液中,滴加全程需在冰浴以及剧烈搅拌下进行。控制滴加速度,使滴加全程耗时3 h。丙烯酰氯滴加完毕后,可撤去冰浴,室温下反应18 h。
反应结束后,将反应产物进行抽滤以除去不溶性杂质,然后利用硅藻土柱层析法吸附副产物三乙胺盐酸盐。利用旋蒸对溶液进行浓缩,然后在剧烈搅拌下将浓缩液缓缓加入1000 mL无水乙醚中,于-20 ℃静置沉降24 h。沉降完毕后,弃去上层清液,对下层沉淀进行抽滤。收集滤渣,真空干燥48 h以上,得中间产物PEGDA大单体(M n 8000)。
将1 g中间产物PEGDA溶解于9 g超纯水中,配制成重量分数为10%的水溶液,然后加入光引发剂0.0005 g D2959,避光搅拌10 min,抽真空以除去溶液中的氧气。将溶液滴加在样品槽中,通入氮气,在波长365 nm、功率15 W的紫外灯下聚合2 h。聚合结束后,用刀片将产物从样品槽中分离出来,得到PEG水凝胶。
将水凝胶置于PBS中浸泡,在37 °C下溶胀48 h,测定出水凝胶的膨胀率约为1.05。
实施例3
首先将一些实验原料进行纯化。二氯甲烷(DCM)用五氧化二磷进行加热回流除水;三乙胺(TEA)用分子筛干燥后蒸馏提纯;丙烯酰氯蒸馏提纯;PEG用共沸法进行除水。
将1 mmol PEG (M n 20000)溶解于100 mL甲苯中,加入少量沸石以防止暴沸,加热至一定温度,利用共沸法在蒸馏出甲苯的同时带走PEG中的水分。待剩下约20 mL甲苯时,停止加热,并冷却至室温。加入120 mL DCM以溶解析出的PEG。在冰浴条件下加入10 mmolTEA。将10 mmol丙烯酰氯用20 mL DCM进行稀释并充分混匀,然后利用滴液漏斗逐滴滴加至PEG溶液中,滴加全程需在冰浴以及剧烈搅拌下进行。控制滴加速度,使滴加全程耗时4 h。丙烯酰氯滴加完毕后,可撤去冰浴,室温下反应24 h。
反应结束后,将反应产物进行抽滤以除去不溶性杂质,然后利用硅藻土柱层析法吸附副产物三乙胺盐酸盐。利用旋蒸对溶液进行浓缩,然后在剧烈搅拌下将浓缩液缓缓加入1000 mL无水乙醚中,于-20℃静置沉降24 h。沉降完毕后,弃去上层清液,对下层沉淀进行抽滤。收集滤渣,真空干燥48 h以上,得中间产物PEGDA大单体(M n 20000)。
将0.5 g中间产物PEGDA溶解于9.5 g超纯水中,配制成重量分数为5%的水溶液,然后加入光引发剂0.00025 g D2959,避光搅拌10 min,抽真空以除去溶液中的氧气。将溶液滴加在样品槽中,通入氮气,在波长365 nm、功率15 W的紫外灯下聚合3 h。聚合结束后,用刀片将产物从样品槽中分离出来,得到PEG水凝胶。
将水凝胶置于PBS中浸泡,在37 °C下溶胀48 h,测定出水凝胶的膨胀率约为1.08。
Claims (5)
1.一种在生理环境中膨胀率极低的高分子水凝胶的制备方法,其特征在于,包括以下步骤:
(1) PEGDA的合成
首先将实验原料进行纯化,二氯甲烷(DCM)用五氧化二磷进行加热回流除水;三乙胺(TEA)用分子筛干燥后蒸馏提纯;丙烯酰氯蒸馏提纯;PEG用共沸法进行除水;
将一定量的PEG溶解于100 mL甲苯中,加入少量沸石以防止暴沸,加热至一定温度,利用共沸法在蒸馏出甲苯的同时带走PEG中的水分,待剩下20 mL甲苯时,停止加热,并冷却至室温,加入120 mL DCM以溶解析出的PEG,在冰浴条件下加入一定量的TEA,TEA与PEG的摩尔比为3:1 ~ 10:1,将一定量的丙烯酰氯用20 mL DCM进行稀释并充分混匀,然后利用滴液漏斗逐滴滴加至PEG溶液中,滴加全程需在冰浴以及剧烈搅拌下进行;丙烯酰氯与PEG的摩尔比为3:1 ~ 10:1,控制滴加速度,使滴加全程耗时2~4 h,丙烯酰氯滴加完毕后,撤去冰浴,室温下反应12~24 h;
反应结束后,将反应产物进行抽滤以除去不溶性杂质,然后利用硅藻土柱层析法吸附副产物三乙胺盐酸盐,利用旋蒸对溶液进行浓缩,然后在剧烈搅拌下将浓缩液缓缓加入1000 mL无水乙醚中,于-20℃静置沉降24 h,沉降完毕后,弃去上层清液,对下层沉淀进行抽滤,收集滤渣,真空干燥48 h以上,得中间产物PEGDA大单体;
(2) 膨胀率极低的水凝胶的制备
将中间产物PEGDA溶解于超纯水中,配制成一定浓度的水溶液,然后加入光引发剂D2959,避光搅拌10 min,抽真空以除去溶液中的氧气,D2959的用量为PEGDA的0.05%,重量比,将溶液滴加在样品槽中,通入氮气,在波长365 nm、功率15 W的紫外灯下聚合1~3 h,聚合结束后,用刀片将产物从样品槽中分离出来,得到水凝胶;
将水凝胶置于PBS中浸泡,在37℃下溶胀48 h,以溶胀后的直径与溶胀前的直径的比值记为水凝胶的膨胀率,筛选出其中膨胀率低于1.10的各种水凝胶。
2.根据权利要求1的一种在生理环境中膨胀率极低的高分子水凝胶的制备方法,其特征在于,所述的PEG的数均分子量为2000、4000、6000、8000、10000、20000、35000中的一种。
3.根据权利要求1的一种在生理环境中膨胀率极低的高分子水凝胶的制备方法,其特征在于 PEGDA水溶液的浓度为3~30 %,重量分数。
4.一种在生理环境中膨胀率极低的高分子水凝胶,其特征在于,根据权利要求1-3任一所述方法制备得到。
5.根据权利要求4所述在生理环境中膨胀率极低的高分子水凝胶在生物医学的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610937144.9A CN106565922B (zh) | 2016-11-01 | 2016-11-01 | 一种在生理环境中膨胀率极低的高分子水凝胶及制备和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610937144.9A CN106565922B (zh) | 2016-11-01 | 2016-11-01 | 一种在生理环境中膨胀率极低的高分子水凝胶及制备和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN106565922A CN106565922A (zh) | 2017-04-19 |
CN106565922B true CN106565922B (zh) | 2018-10-16 |
Family
ID=58534600
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610937144.9A Active CN106565922B (zh) | 2016-11-01 | 2016-11-01 | 一种在生理环境中膨胀率极低的高分子水凝胶及制备和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106565922B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111150878B (zh) * | 2018-11-07 | 2022-03-15 | 财团法人工业技术研究院 | 生物可分解的封合胶及其用途 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7670616B2 (en) * | 2004-03-11 | 2010-03-02 | Cornell Research Foundation, Inc. | Hydrogel forming system comprising PEG derivative precursor |
CN103230619B (zh) * | 2013-05-15 | 2014-11-26 | 南京斯瑞奇医疗用品有限公司 | 复合水凝胶敷料及其制备方法 |
CN103435761B (zh) * | 2013-08-20 | 2015-10-07 | 中科院广州化学有限公司 | 一种复合交联剂智能水凝胶及其制备方法与应用 |
-
2016
- 2016-11-01 CN CN201610937144.9A patent/CN106565922B/zh active Active
Also Published As
Publication number | Publication date |
---|---|
CN106565922A (zh) | 2017-04-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Ye et al. | Self-healing pH-sensitive cytosine-and guanosine-modified hyaluronic acid hydrogels via hydrogen bonding | |
Lim et al. | New visible-light photoinitiating system for improved print fidelity in gelatin-based bioinks | |
JP2020139163A (ja) | 官能性双性イオン性ポリマーおよび混合電荷ポリマー、関連するヒドロゲルならびにこれらの使用方法 | |
EP3727488B1 (en) | Hydrogels based on blood plasma components, process and uses thereof | |
WO2012057751A1 (en) | Crosslinked cellulosic polymers | |
Schoolaert et al. | Waterborne electrospinning of poly (N-isopropylacrylamide) by control of environmental parameters | |
CN111019162A (zh) | 以氧化透明质酸为交联剂的壳聚糖多肽衍生物自交联水凝胶的制备方法及应用 | |
KR20150082619A (ko) | 히알루론산의 광반응성 유도체, 이의 제조 방법, 히알루론산의 3d-가교된 유도체, 이의 제조 방법 및 용도 | |
Hwang et al. | Tough antibacterial metallopolymer double-network hydrogels via dual polymerization | |
Jain et al. | Poly (ectoine) hydrogels resist nonspecific protein adsorption | |
Wang et al. | Stack-based hydrogels with mechanical enhancement, high stability, self-healing property, and thermoplasticity from poly (l-glutamic acid) and ureido-pyrimidinone | |
CN102634043A (zh) | 一种超分子水凝胶及其制备方法和应用 | |
CN108484936A (zh) | 一种接枝改性材料所制备的水凝胶及其制备方法和应用 | |
Joshi et al. | Bioinspired adenine–dopamine immobilized polymer hydrogel adhesives for tissue engineering | |
CN106565922B (zh) | 一种在生理环境中膨胀率极低的高分子水凝胶及制备和应用 | |
Lüchow et al. | Modular, synthetic, thiol‐ene mediated hydrogel networks as potential scaffolds for 3D cell cultures and tissue regeneration | |
Koda et al. | One-shot preparation of polyacrylamide/poly (sodium styrenesulfonate) double-network hydrogels for rapid optical tissue clearing | |
CN104744717B (zh) | 一种光固化制备磷酰胆碱仿生涂层的方法 | |
Luo et al. | Novel THTPBA/PEG‐derived highly branched polyurethane scaffolds with improved mechanical property and biocompatibility | |
CN107446085A (zh) | 一种水下自愈合水凝胶的制备方法 | |
Moriwaki et al. | Phospholipid polymer hydrogels with rapid dissociation for reversible cell immobilization | |
CN107899078A (zh) | 一种在三维支架表面共价键合生物活性层的方法 | |
Lambrecht et al. | Swelling Behavior of Novel Hydrogels Produced from Glucose-Based Ionic Monomers with Varying Cross-Linkers | |
CN104211850A (zh) | 一种含可逆氢键的梳型聚合物及其制备方法 | |
CN108676179B (zh) | 一种基于酶交联的聚乙二醇类化学水凝胶及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right |
Effective date of registration: 20230825 Address after: 201306 C Building, 888 Huanhu West Second Road, Pudong New Area, Shanghai Patentee after: Shanghai Helan Nanotechnology Co.,Ltd. Address before: 200241 No. 28 East Jiangchuan Road, Shanghai, Minhang District Patentee before: SHANGHAI NATIONAL ENGINEERING RESEARCH CENTER FOR NANOTECHNOLOGY Co.,Ltd. |
|
TR01 | Transfer of patent right |