CN112898532B - 一种磁性聚合物水凝胶及其制备方法和应用 - Google Patents
一种磁性聚合物水凝胶及其制备方法和应用 Download PDFInfo
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- CN112898532B CN112898532B CN202110074054.2A CN202110074054A CN112898532B CN 112898532 B CN112898532 B CN 112898532B CN 202110074054 A CN202110074054 A CN 202110074054A CN 112898532 B CN112898532 B CN 112898532B
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Abstract
本发明涉及高分子材料制备技术领域,具体涉及一种磁性聚合物水凝胶及其制备方法和应用。二异氰酸酯、聚乙二醇与催化剂在N,N‑二甲基甲酰胺溶剂中反应得到双端异氰酸基聚合物预聚物,然后加入含醛基的双端二羟基化合物,得到侧链为醛基的聚合物溶液,在溶液中加入氨基改性的磁性纳米粒子交联,经去离子水浸泡,多次换水,得到一种磁性聚合物水凝胶。通过该方法制备所得到的水凝胶具有良好的力学性能,其压缩强度可达0.49‑0.96MPa,且在磁场的作用下,可以作为药物载体定向缓释,效果可维持1‑3周。
Description
技术领域
本发明涉及高分子材料制备技术领域,具体涉及一种磁性聚合物水凝胶及其制备方法和应用。
背景技术
公开该背景技术部分的信息仅仅旨在增加对本发明的总体背景的理解,而不必然被视为承认或以任何形式暗示该信息构成已经成为本领域一般技术人员所公知的现有技术。
聚合物(PU)是主链上含有氨基甲酸酯基团(-NHCOO-)的高分子聚合物,可以通过使用脂肪族或芳香族异氰酸酯类化合物和大分子多元醇以及小分子醇类或胺类扩链剂来合成具有所需功能的合成材料。聚合物是一种独特的材料,其性能和应用十分广泛,因为它们可以通过选择不同组成单体而适用于各种特定的应用。近年来,聚合物因其具有优异的力学性能和较好的生物相容性,同时具有原料种类的多样性、配方的多样性的特点,使得聚合物设计自由度高、性能调控范围广,是制备高性能水凝胶的理想材料。
近几年关于磁性聚合物材料的研究取得了较大进展,赋予聚合物以磁性可以改善聚合物的吸附性能、亲水性能及强度;同时,磁性粒子可以使整个载体带有较强的磁场,其产生的物理、化学以及生物磁致效应,有利于产品的回收再利用,因此合成了许多带有磁性的聚合物材料。具有磁性的水凝胶近年来也是人们研究的热门课题,在药物释放、光子晶体、驱动器和人造肌肉等方面均展现出良好的应用前景。多孔结构的磁性水凝胶在磁场下可发生高达70%的体积变形,使得药物随着水分被排挤出来,磁场下的药物释放量是无磁场下的7倍,并且可以实现干细胞在小鼠体内的可控释放。
因其较好的生物相容性,聚合物水凝胶在创面敷料、药物载体、医疗器械等领域已获得广泛的应用。但是传统的聚合物水凝胶很难回收再利用,如果在聚合物中加入磁性纳米Fe3O4,在通过外加磁场,就可以实现对聚合物水凝胶材料回收再利用,然而纳米Fe3O4与聚合物水凝胶的相容性很差,一般通过物理共混的方法,会使纳米Fe3O4与聚合物结合不紧密,纳米Fe3O4很容易脱落,使得聚合物水凝胶的磁性减弱且磁性保留时间不长,使该种聚合物的可回收性大大降低。
一些现有技术利用原位沉淀法得到均匀分布的磁性粒子,另外利用聚合物高分子网络在高浓度氢氧化钠溶液中的体积相变,得到高强度高断裂韧性的磁性水凝胶。但由于采用N,N-二甲基丙烯酰胺单体复合制备水凝胶,直接的皮肤接触及吞食有害,故该制备方法生物相容性较差。也有一些技术提供工艺简单、持久抗菌、组分配比可调的抗菌聚合物水凝胶医用敷料,但其产品无磁性,缺乏有效的回收再利用方法和途径。在一些磁性聚合物制备方法中,由于Fe3O4和磁性扩链剂的限制,简单的共混使得纳米Fe粒子与主链结合力差,随着时间的延长,产物的磁性会迅速下降。
发明人发现,目前的聚合物制备方法中存在无法有效的、能长时间保持磁性的缺点,或存在对人体有害,生物相容性差的缺点。特别是作为载药水凝胶,难以实现对药物释放量的有效控制。
发明内容
针对上述现有技术中存在的Fe粒子与主链结合力差、磁性不稳定以及生物相容性差的问题,本发明提供一种磁性聚合物水凝胶及其制备方法和应用。首先合成侧链含有醛基的聚合物预聚物,通过氨基改性的磁性纳米粒子交联,经后处理得磁性聚合物水凝胶。通过化学共价键的修饰,大幅改善了磁性纳米粒子与聚合物之间的相容性,使得以磁性纳米粒子与聚合物结合非常紧密,解决了一般物理共混中易脱落的难题,同时赋予了聚合物优异的磁性和生物相容性。
具体地,本发明是通过如下所述的技术方案实现的:
本发明第一方面,提供一种侧链含醛基的聚合物,结构式如下:
其中,R1选自C1-C6的直链或支链烷基、烷氧基,取代或未取代芳香基,取代或未取代的甲基环戊烷基,取代或未取代的乙基环戊烷基,取代或未取代的甲基环己烷基,取代或未取代的乙基环己烷基,二对甲苯基甲烷基,二对甲苯基乙烷基;
所述取代选自C1-C6直链或支链烷基、烷氧基,单取代或多取代;
R2选自醛基取代的C1-C6直链或支链烷基、烷氧基,取代或未取代的醛基芳香基,芳香基取代为单取代或多取代,取代基为C1-C6直链或支链烷基、烷氧基和卤素;
n=91-455,m=5-25;
所述侧链含醛基的聚合物的重均分子量为2×104~5×105g/mol。
本发明第二方面,提供一种侧链含醛基的聚合物的制备方法,所述方法包括:二异氰酸酯、聚乙二醇和催化剂溶解在溶剂中,搅拌,升温,进行反应,得到双端异氰酸基聚合物预聚物溶液,向双端异氰酸基聚合物预聚物溶液中加入含醛基的双端二羟基化合物并搅拌均匀,继续保温,进行反应,即得。
本发明第三方面,提供一种磁性聚合物水凝胶,包括侧链含醛基的聚合物和氨基改性的磁性纳米粒子。
本发明第四方面,提供一种磁性聚合物水凝胶的制备方法,所述方法包括:
在溶剂中加入氨基改性的磁性纳米粒子,超声分散,将其加入到同一溶剂稀释后的侧链含醛基的聚合物溶液中,静置,待反应结束后,得到磁性聚合物凝胶,将制备的磁性聚合物凝胶在去离子水中浸泡,定期换水,即得磁性聚合物水凝胶。
本发明第五方面,提供一种载药水凝胶,包括磁性聚合物水凝胶和药物。
本发明第六方面,提供一种载药水凝胶的制备方法,其所述方法包括:将制备好的磁性聚合物水凝胶冷冻干燥,得到干凝胶,将干凝胶浸泡于已溶有药物有效成分的去离子水中,得到载药水凝胶。
本发明第七方面,提供一种侧链含醛基的聚合物和/或磁性聚合物水凝胶和/ 或载药水凝胶在磁性复合材料或载药水凝胶领域的应用。
本发明的一个或多个实施例具有以下有益效果:
1)本发明磁性聚合物的制备方法,原料易得,操作简单方便、实用性强,易于推广与应用。
2)本发明磁性聚合物水凝胶的制备方法中,通过化学共价键的修饰,而非物理共混的方法,大幅改善了磁性纳米粒子与聚合物之间的相容性,使得以磁性纳米粒子为交联中心,与聚合物结合非常紧密,解决了一般物理共混中易脱落的难题,同时赋予了聚合物优异的磁性。
3)本发明提供的聚合物水凝胶主要由二异氰酸酯链段和聚乙二醇链段组成,均具有良好的生物相容性,作为药物载体不会对有机体产生危害。
4)本发明提供的聚合物水凝胶可以作为药物载体,并在磁性条件下可实现对特定位置的病变细胞定向给药。
5)本发明的水凝胶以磁性纳米粒子为交联中心,形成的分子网络大小统一,加上聚合物氢键的作用,三维网络更稳定,具有良好的机械性能,其压缩强度可达0.49-0.96MPa,且作为药物载体缓释效果可维持1-3周。
附图说明
构成本发明的一部分的说明书附图用来提供对本发明的进一步理解,本发明的示意性实施例及其说明用于解释本发明,并不构成对本发明的不当限定。以下,结合附图来详细说明本发明的实施方案,其中:
图1为本发明实施例1制备得磁性聚合物水凝胶G1在不同磁场强度下的药物释放与时间关系图。
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。下列实施例中未注明具体条件的实验方法,通常按照常规条件或按照制造厂商所建议的条件。
除非另行定义,文中所使用的所有专业与科学用语与本领域熟练人员所熟悉的意义相同。此外,任何与所记载内容相似或均等的方法及材料皆可应用于本发明方法中。文中所述的较佳实施方法与材料仅作示范之用。
为了解决现有磁性聚合物制备方法中存在无法有效的、能长时间保持磁性的缺点,或存在对人体有害,生物相容性差的缺点,本发明提出一种磁性聚合物水凝胶及其制备方法和应用。
具体地,通过以下技术方案实现:
在本发明的第一方面,提供一种侧链含醛基的聚合物,结构式如下:
其中,R1选自C1-C6的直链或支链烷基、烷氧基,取代或未取代芳香基,取代或未取代的甲基环戊烷基,取代或未取代的乙基环戊烷基,取代或未取代的甲基环己烷基,取代或未取代的乙基环己烷基,二对甲苯基甲烷基,二对甲苯基乙烷基;
所述取代选自C1-C6直链或支链烷基、烷氧基,单取代或多取代;
R2选自醛基取代的C1-C6直链或支链烷基、烷氧基,取代或未取代的醛基芳香基,芳香基取代为单取代或多取代,取代基为C1-C6直链或支链烷基、烷氧基和卤素;
n=91-455,m=5-25。
所述侧链含醛基的聚合物的重均分子量为2×104~5×105g/mol。
在本发明的一个或多个实施例中,所述R1选自甲基、乙基、丙基、丁基、戊基、己基,1,2苯基,1,3苯基,1,4苯基,1,3取代苯基,所述取代选自C1-C6 直链或支链烷基、烷氧基,单取代或多取代,取代位点为4、5、6位,优选为4 位;
所述取代进一步优选为4-甲基、4-乙基、4-丙基、4-异丙基;
优选地,R1选自取代或未取代的1-甲基-3-环戊烷基,取代或未取代的1-乙基-3-环戊烷基,取代或未取代的1-甲基-3-环己烷基,取代或未取代的1-乙基-3- 环己烷基,所述取代优选为1,5,5-三甲基取代;
R2选自醛基取代的C1-C6直链或支链烷基、烷氧基,取代或未取代的醛基芳香基,芳香基取代为单取代或多取代,取代基为C1-C6直链或支链烷基、烷氧基和卤素;
优选地,所述R2选自醛基取代的C1-C4直链或支链烷基、烷氧基,进一步优选为醛基取代甲基或醛基取代乙基;
优选地,所述R2选自取代或未取代的2,4醛基苯基,2,3醛基苯基,3,6醛基苯基,
取代2,3醛基苯基中所述取代位点为4、5、6位,优选为4位,取代原子为卤素,优选为氟、氯、溴、碘。
n=91-455,m=5-25,进一步优选为n=160-273,m=8-21;
进一步优选地,
在本发明的第二方面,提供一种侧链含醛基的聚合物的制备方法,所述方法包括:二异氰酸酯、聚乙二醇和催化剂溶解在溶剂中,搅拌,升温,进行反应,得到双端异氰酸基聚合物预聚物溶液,向双端异氰酸基聚合物预聚物溶液中加入含醛基的双端二羟基化合物并搅拌均匀,继续保温,进行反应,即得。
侧链含醛基的聚合物的制备方法制备得到的侧链含醛基的聚合物的。
在本发明的一个或多个实施例中,所述溶剂选自N,N-二甲基甲酰胺,N,N- 二甲基乙酰胺,二甲基亚砜;
优选地,所述二异氰酸酯为脂肪族二异氰酸酯和芳香族二异氰酸酯,进一步优选为脂肪族二异氰酸酯、异佛尔酮二异氰酸酯、甲苯二异氰酸酯、二苯基甲烷二异氰酸酯;
优选地,催化剂为锡类催化剂,加入量为二异氰酸酯和聚乙二醇的总质量的 0.1-1%;优选的,催化剂选自二月桂酸二丁锡或辛酸亚锡;
优选地,聚乙二醇的分子量范围为2000-100000,优选为4000-20000,进一步优选为8000或10000或12000;聚乙烯醇分子量过大或过小,会影响其粘度,进而影响侧链含醛基的聚合物的性能。
优选地,聚乙二醇与二异氰酸酯摩尔比为1:1.25-2;进一步优选为1:2;
优选地,通过二正丁胺法测定-NCO含量达到理论值判断聚乙二醇与二异氰酸酯的反应终点;
优选地,双端异氰酸基聚合物预聚物在溶剂中的质量浓度为60-80%;
优选地,所述含醛基的双端二羟基化合物包括但不限于2,3-二羟基丙醛,2,4- 二羟基苯甲醛、4-溴-2,3-二羟基苯甲醛、2,5-二羟基苯甲醛,进一步优选为2,3- 二羟基丙醛或2,4-二羟基苯甲醛;
优选地,二异氰酸酯、聚乙二醇和催化剂在溶剂中升温至70-95℃,反应2-4h,进一步优选为80-90℃,反应2.5-3.5h;
向聚合物预聚物溶液中加入含醛基的双端二羟基化合物,维持温度为 70-95℃,反应2-4h,进一步优选为80-90℃,反应2.5-3.5h;
优选地,含醛基的双端二羟基化合物的加入摩尔量计算公式如下:
N含醛基的双端二羟基化合物=n二异氰酸酯—n聚乙二醇。
优选地,制备所得侧链含醛基的聚合物的质量浓度为60-80%;
在本发明的第三方面,提供一种磁性聚合物水凝胶,包括侧链含醛基的聚合物和氨基改性的磁性纳米粒子。
在本发明的第四方面,提供一种磁性聚合物水凝胶的制备方法,所述方法包括:
在溶剂中加入氨基改性的磁性纳米粒子,超声分散,将其加入到同一溶剂稀释后的侧链含醛基的聚合物溶液中,静置,待反应结束后,得到磁性聚合物凝胶,将制备的磁性聚合物凝胶在去离子水中浸泡,定期换水,即得磁性聚合物水凝胶。
在本发明的一个或多个实施例中,所述溶剂为丙酮、N,N-二甲基甲酰胺, N,N-二甲基乙酰胺,二甲基亚砜;
优选地,氨基改性的磁性纳米粒子量为二异氰酸酯和聚乙二醇的总质量的0.5%-3%;
优选地,超声分散时间为20-40min,进一步优选为25-35min;
优选地,稀释后的侧链含醛基的聚合物溶液质量浓度范围为50-70%。
优选地,静置条件为在2-18℃条件下静置反应3-5h,进一步优选为8℃条件下静置反应4h;
优选地,磁性聚合物凝胶在去离子水浸泡7天,每隔12h换一次水;
优选地,侧链含醛基的聚合物与氨基改性的磁性纳米粒子的反应终点,通过 FT-IR检测-CHO在1760-1640cm-1红外吸收峰彻底消失;
优选地,将制备好的磁性聚合物水凝胶冷冻干燥,也可得到干凝胶。
磁性纳米粒子的制备方法按照文献(Lei Yang等.Preparation of novelhydrophobic magnetic Fe3O4/waterborne polyurethane nanocomposites.Journal ofApplied Polymer Science,2020,137(15):48546)所述,并以全文的方式引入本发明中,制备方法如下:
将0.54g四水合氯化亚铁和1.42g六水合三氯化铁固体,在80℃下,溶解在160mL去离子水中。在超声波下,将1,6-己二胺加入到上述溶液中搅拌1.5h,将混合物的反应温度保持在80℃充分反应。待反应结束后,通过磁分离将氨基改性的磁性纳米粒子从反应体系中分离出来,用去离子水和乙醇洗涤三次,并在真空条件下干燥12h。
在本发明的第五方面,提供一种载药水凝胶,包括磁性聚合物水凝胶和药物;
优选地,所述药物选自抗菌药、消炎止痛药物或促进创面愈合药物,进一步优选为头孢布烯、红霉素、吲哚美辛、艾瑞昔布。
在本发明的第六方面,提供一种载药水凝胶的制备方法,所述方法包括:将制备好的磁性聚合物水凝胶冷冻干燥,得到干凝胶,将干凝胶浸泡于已溶有药物有效成分的去离子水中,得到载药水凝胶;
优选地,将干凝胶浸泡于已溶有药物有效成分的去离子水中10-18h,进一步优选为12h;
优选地,干凝胶质量为5-20g,进一步优选为10g;
优选地,药物有效成分浓度为0.001-0.3mg/mL,优选为0.2mg/mL。
在本发明的第七方面,提供一种侧链含醛基的聚合物和/或磁性聚合物水凝胶和/或载药水凝胶在磁性复合材料或载药水凝胶领域的应用。
下面结合具体的实施例,对本发明做进一步的详细说明,应该指出,所述具体实施例是对本发明的解释而不是限定。
实施例1
步骤1:支链含醛基的聚合物的制备:
将2.22g异佛尔酮二异氰酸酯、50g真空脱水后的聚乙二醇(分子量为10000) 和0.1g二月桂酸二丁基锡溶于30mL DMF,搅拌均匀,升温至85℃恒温反应,至用二正丁胺滴定法测定体系中-NCO含量达到理论值,反应时间约3h,得到双端异氰酸基聚合物预聚物溶液。向聚合物预聚物溶液中加入0.45g 2,3-二羟基丙醛,搅拌均匀,维持85℃反应约3h,得到质量浓度约64.4%支链含醛基的聚合物(BAPU)溶液。
步骤2:磁性聚合物水凝胶的制备:
a.在20mL丙酮中加入0.67g氨基改性的磁性纳米粒子,超声分散30min,得到分散均匀的氨基改性的磁性纳米粒子溶液。
b.在步骤1已制备好的81.12g的BAPU溶液中加入20mL丙酮调节反应溶液的粘度,加入氨基改性的磁性纳米粒子溶液,在8℃条件下静置反应约4h,得到磁性聚合物凝胶(MPU)。
c.将制备的MPU在去离子水浸泡7天,每隔12h换一次水,得磁性聚合物水凝胶(MPU-W),记作G1。
实施例2
步骤1:支链含醛基的聚合物的制备:
将2.22g异佛尔酮二异氰酸酯、60g真空脱水后的聚乙二醇(分子量为10000) 和0.1g辛酸亚锡溶于30mL DMF,搅拌均匀,升温至90℃恒温反应,至用二正丁胺滴定法测定体系中-NCO含量达到理论值,反应时间约2.5h,得到双端异氰酸基聚合物预聚物溶液。向聚合物预聚物溶液中加入0.36g 2,3-二羟基丙醛,搅拌均匀,维持90℃反应约2.5h,得到质量浓度约为68.4%的支链含醛基的聚合物 (BAPU)溶液。
步骤2:磁性聚合物水凝胶的制备:
a.在20mL丙酮中加入0.67g氨基改性的磁性纳米粒子,超声分散30min,得到分散均匀的氨基改性的磁性纳米粒子溶液。
b.在步骤1已制备好的91.03g的BAPU溶液中加入20mL丙酮调节反应溶液的粘度,加入氨基改性的磁性纳米粒子溶液,在8℃条件下静置反应约4h,得到磁性聚合物凝胶(MPU)。
c.将制备的MPU在去离子水浸泡7天,每隔12h换一次水,得磁性聚合物水凝胶(MPU-W),记作G2。
实施例3
将1.68g六亚甲基二异氰酸酯、70g真空脱水后的聚乙二醇(分子量为8000) 和0.09g二月桂酸二丁基锡溶于30mL DMF,搅拌均匀,升温至80℃恒温反应,至用二正丁胺滴定法测定体系中-NCO含量达到理论值,反应时间约3.5h,得到双端异氰酸基聚合物预聚物溶液。向聚合物预聚物溶液中加入0.27g 2,3-二羟基丙醛,搅拌均匀,维持80℃反应约3.5h,得到质量浓度约为71.4%的BAPU溶液。
步骤2:磁性聚合物水凝胶的制备:
a.在20mL丙酮中加入0.67g氨基改性的磁性纳米粒子,超声分散35min,得到分散均匀的氨基改性的磁性纳米粒子溶液。
b.在步骤1已制备好的100.39g的BAPU溶液中加入20mL丙酮调节反应溶液的粘度,加入氨基改性的磁性纳米粒子溶液,在8℃条件下静置反应约4h,得到磁性聚合物凝胶(MPU)。
c.将制备的MPU在去离子水浸泡7天,每隔12h换一次水,得磁性聚合物水凝胶(MPU-W),记作G3。
实施例4
步骤1:支链含醛基的聚合物的制备:
将2.22g异佛尔酮二异氰酸酯、50g真空脱水后的聚乙二醇(分子量为10000) 和0.11g二月桂酸二丁基锡溶于25mL DMF,搅拌均匀,升温至85℃恒温反应,至用二正丁胺滴定法测定体系中-NCO含量达到理论值,反应时间约2.5h,得到双端异氰酸基聚合物预聚物溶液。向聚合物预聚物溶液中加入0.45g 2,3-二羟基丙醛,搅拌均匀,维持90℃反应约3h,得到质量浓度约为68.4%的支链含醛基的聚合物(BAPU)溶液。重复上述过程,制备三份相同的BAPU溶液。
步骤2:磁性聚合物水凝胶的制备:
a.在20mL丙酮中加入0.67g氨基改性的磁性纳米粒子,超声分散25min,得到分散均匀的氨基改性的磁性纳米粒子溶液。
b.在三份步骤1已制备好的质量为76.40g的BAPU溶液中分别加入10、20、 30mL丙酮调节反应溶液的粘度,加入氨基改性的磁性纳米粒子溶液,在8℃条件下静置反应约4h,得到三份质量浓度不同的磁性聚合物凝胶(MPU)。
c.将制备的MPU在去离子水浸泡7天,每隔12h换一次水,得磁性聚合物水凝胶(MPU-W),分别记作G4-Ⅰ、G4-Ⅱ、G4-Ⅲ。
实施例5
步骤1:支链含醛基的聚合物的制备:
将2.22g异佛尔酮二异氰酸酯、50g真空脱水后的聚乙二醇(12000)和0.1g 二月桂酸二丁基锡溶于35mL DMF,搅拌均匀,升温至90℃恒温反应,至用二正丁胺滴定法测定体系中-NCO含量达到理论值,反应时间约3h,得到双端异氰酸基聚合物预聚物溶液。向聚合物预聚物溶液中加入0.69g 2,4-二羟基苯甲醛,搅拌均匀,维持85℃反应约3.5h,得到质量浓度约为60.7%的支链含醛基的聚合物(BAPU)溶液。重复上述过程,制备三份相同的BAPU溶液。
步骤2:磁性聚合物水凝胶的制备:
a.在20mL丙酮中分别加入0.32、0.67、1.06g氨基改性的磁性纳米粒子,超声分散30min,得到三份浓度不同的氨基改性的磁性纳米粒子溶液。
b.在三份步骤1已制备好的质量为86.08g的BAPU溶液中加入20mL丙酮调节反应溶液的粘度,分别加入不同浓度的氨基改性的磁性纳米粒子溶液,在4℃条件下静置反应约3.5h,得到三份磁性聚合物凝胶(MPU)。
c.将制备的MPU在去离子水浸泡7天,每隔12h换一次水,得磁性聚合物水凝胶(MPU-W),分别记作G5-Ⅰ、G5-Ⅱ、G5-Ⅲ。
分析与说明:以下分析方法用于所有实施例,除非另外说明。
药物缓释性能:取10g MPU的干凝胶浸泡于不同体积的已溶有头孢布烯的去离子水中(头孢布烯浓度:0.2mg/mL)12h,得到载药水凝胶,取5g载药水凝胶泡置于50mL磷酸缓冲溶液中,每隔一段时间取缓冲溶液测其紫外吸收,通过吸光度-浓度吸收曲线计算出释放头孢布烯的量。
取4份等质量的磁性聚合物水凝胶G1浸泡在pH=5.5的溶液中,分别置于 0kOe、1.0kOe、3.0kOe、5.0kOe外加磁场下,每隔一段时间测介质的紫外吸收,通过标准紫外吸光度-浓度吸收曲线计算出释放10-羟基喜树碱的含量。测定结果如图1。结果表明本实施例的磁性聚合物水凝胶能够通过控制磁场对药物的释放产生影响,当磁场强度较小时,药物缓释速率较为平缓,释放时间长,释放量也较低,20天后释放量仅达到80%。当施加较大的磁场强度时,其释放速率快,释放量在5天时可达到80%以上。这说明该磁性聚合物水凝胶可实现对药物释放量的精准控制。
压缩性能:
为了比较不同条件下水凝胶的抗压性能,在有一定的压力条件下,需对水凝胶的抗压性能进行测试,测试结果如表1所示:
表1不同条件下水凝胶的抗压性能测试结果
从表1中可以看出水凝胶的压缩模量变化较大,水凝胶的压缩测试是以样品没有被压碎破裂为前提的,压缩模量越大说明水凝胶具有良好的韧性。通过表1 显示,样品G1-G3显示水凝胶的压缩模量和压缩强度随着含醛基化合物的含量的降低而呈现降低的趋势。这可能是因为随着醛基含量的降低,聚合物大分子链之间的交联度下降使得水凝胶的压缩强度和压缩模量降低。实施例4中经探究后呈现出随着水凝胶浓度的降低而导致其压缩性能与压缩模量的下降,这可能是浓度越低,产生气泡越大,形成水凝胶后内部有较多松散且不均匀的孔洞,导致其抗压性能降低。实施例5中经探究后呈现出随着加入磁性纳米粒子的量增加,水凝胶压缩强度增高,这可能是因为随着磁性纳米粒子的增加,除磁性纳米粒子的氨基与聚合物的醛基形成共价键,还有可能磁性纳米子与聚合物链间存在氢键作用,进一步提高了交联密度,增强水凝胶的压缩强度与压缩模量。
本说明书中各个实施例采用递进的方式描述,每个实施例重点说明的都是与其他实施例的不同之处,各个实施例之间相同相似部分互相参见即可。
以上所述仅为本发明的优选实施例而已,并不用于限制本发明,尽管参照前述实施例对本发明进行了详细的说明,对于本领域的技术人员来说,其依然可以对前述各实施例所记载的技术方案进行修改,或者对其中部分技术特征进行等同替换。凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (35)
1.一种磁性聚合物水凝胶,其特征在于,包括一种侧链含醛基的聚合物和氨基改性的磁性纳米粒子;
所述侧链含醛基的聚合物,其特征在于,结构式如下:
所述的磁性聚合物水凝胶的制备方法,其特征在于,所述方法包括:
在溶剂中加入氨基改性的磁性纳米粒子,超声分散,将其加入到同一溶剂稀释后的侧链含醛基的聚合物溶液中,静置,待反应结束后,得到磁性聚合物凝胶,将制备的磁性聚合物凝胶在去离子水中浸泡,定期换水,即得磁性聚合物水凝胶;
所述的磁性聚合物水凝胶和药物制备一种载药水凝胶;
n=91-455,m=5-25;
所述侧链含醛基的聚合物的重均分子量为2×104~5×105g/mol。
2.根据权利要求1所述的磁性聚合物水凝胶,其特征在于,所述侧链含醛基的聚合物中,n=160-273,m=8-21。
3.根据权利要求1所述的磁性聚合物水凝胶,其特征在于,所述的侧链含醛基的聚合物的制备方法包括:二异氰酸酯、聚乙二醇和催化剂溶解在溶剂中,搅拌,升温,进行反应,得到双端异氰酸基聚合物预聚物溶液,向双端异氰酸基聚合物预聚物溶液中加入含醛基的双端二羟基化合物并搅拌均匀,继续保温,进行反应,即得。
4.根据权利要求3所述的磁性聚合物水凝胶,其特征在于,所述溶剂选自N,N-二甲基甲酰胺,N,N-二甲基乙酰胺,二甲基亚砜。
5.根据权利要求3所述的磁性聚合物水凝胶,其特征在于,所述二异氰酸酯为脂肪族二异氰酸酯和芳香族二异氰酸酯。
6.根据权利要求5所述的磁性聚合物水凝胶,其特征在于,所述二异氰酸酯为异佛尔酮二异氰酸酯、甲苯二异氰酸酯、二苯基甲烷二异氰酸酯、六亚甲基二异氰酸酯。
7.根据权利要求3所述的磁性聚合物水凝胶,其特征在于,所述催化剂为锡类催化剂,加入量为单体总质量的0.1-1%。
8.根据权利要求7所述的磁性聚合物水凝胶,其特征在于,所述催化剂为二月桂酸二丁锡或辛酸亚锡。
9.根据权利要求3所述的磁性聚合物水凝胶,其特征在于,所述聚乙二醇的分子量范围为2000-100000。
10.根据权利要求9所述的磁性聚合物水凝胶,其特征在于,所述聚乙二醇的分子量范围为4000-20000。
11.根据权利要求10所述的磁性聚合物水凝胶,其特征在于,所述聚乙二醇的分子量范围为8000或10000或12000。
12.根据权利要求3所述的磁性聚合物水凝胶,其特征在于,所述聚乙二醇与二异氰酸酯摩尔比为1:1.25-2。
13.根据权利要求12所述的磁性聚合物水凝胶,其特征在于,所述聚乙二醇与二异氰酸酯摩尔比为1:2。
14.根据权利要求3所述的磁性聚合物水凝胶,其特征在于,通过二正丁胺法测定-NCO含量达到理论值判断聚乙二醇与二异氰酸酯的反应终点。
15.根据权利要求3所述的磁性聚合物水凝胶,其特征在于,双端异氰酸基聚合物预聚物在溶剂中的质量浓度为35-60%。
16.根据权利要求15所述的磁性聚合物水凝胶,其特征在于,双端异氰酸基聚合物预聚物在溶剂中的质量浓度为40-55%。
17.根据权利要求3所述的磁性聚合物水凝胶,其特征在于,所述含醛基的双端二羟基化合物包括但不限于2,3-二羟基丙醛,2,4-二羟基苯甲醛、4-溴-2,3-二羟基苯甲醛、2,5-二羟基苯甲醛。
18.根据权利要求17所述的磁性聚合物水凝胶,其特征在于,所述含醛基的双端二羟基化合物为2,3-二羟基丙醛,2,4-二羟基苯甲醛。
19.根据权利要求3所述的磁性聚合物水凝胶,其特征在于,二异氰酸酯、聚乙二醇和催化剂在溶剂中升温至70-95℃,反应2-4h。
20.根据权利要求19所述的磁性聚合物水凝胶,其特征在于,二异氰酸酯、聚乙二醇和催化剂在溶剂中升温至80-90℃,反应2.5-3.5h。
21.根据权利要求3所述的磁性聚合物水凝胶,其特征在于,向聚合物预聚物溶液中加入含醛基的双端二羟基化合物,维持温度为70-95℃,反应2-4h。
22.根据权利要求21所述的磁性聚合物水凝胶,其特征在于,所述温度为80-90℃,反应2.5-3.5h。
23.根据权利要求3所述的磁性聚合物水凝胶,其特征在于,含醛基的双端二羟基化合物的加入摩尔量计算公式如下:
N含醛基的双端二羟基化合物= n二异氰酸酯— n聚乙二醇。
24.根据权利要求3所述的磁性聚合物水凝胶,其特征在于,制备所得侧链含醛基的聚合物的质量浓度为60-80%。
25.根据权利要求1所述的磁性聚合物水凝胶,其特征在于,所述的磁性聚合物水凝胶的制备方法,其特征在于,所述溶剂为丙酮、N,N-二甲基甲酰胺,N,N-二甲基乙酰胺,二甲基亚砜;氨基改性的磁性纳米粒子量为反应物总质量的0.5%-3%;超声分散时间为20-40min;稀释后的侧链含醛基的聚合物溶液质量浓度范围为50-70%;静置条件为在2-18℃条件下静置反应3-5h;磁性聚合物凝胶在去离子水浸泡7天,每隔12h换一次水。
26.根据权利要求25所述的磁性聚合物水凝胶,其特征在于,所述超声分散时间为25-35min;所述静置条件为8℃条件下静置反应4h。
27.根据权利要求1所述的磁性聚合物水凝胶,其特征在于,将制备好的磁性聚合物水凝胶冷冻干燥,也可得到干凝胶。
28.根据权利要求1所述的磁性聚合物水凝胶,其特征在于,所述药物选自抗菌药、消炎止痛药物或促进创面愈合药物。
29.根据权利要求28所述的磁性聚合物水凝胶,其特征在于,所述药物选为头孢布烯、红霉素、吲哚美辛、艾瑞昔布。
30.根据权利要求1所述的磁性聚合物水凝胶,其特征在于,所述载药水凝胶的制备方法包括:将制备好的磁性聚合物水凝胶冷冻干燥,得到干凝胶,将干凝胶浸泡于已溶有药物有效成分的去离子水中,得到载药水凝胶。
31.根据权利要求30所述的磁性聚合物水凝胶,其特征在于,将干凝胶浸泡于已溶有药物有效成分的去离子水中10-18h。
32.根据权利要求31所述的磁性聚合物水凝胶,其特征在于,将干凝胶浸泡于已溶有药物有效成分的去离子水中12h。
33.根据权利要求1所述的磁性聚合物水凝胶,其特征在于,所述药物有效成分浓度为0.001-0.3mg/mL。
34.根据权利要求33所述的磁性聚合物水凝胶,其特征在于,所述药物有效成分浓度为0.2mg/mL。
35.权利要求1所述的磁性聚合物水凝胶在磁性复合材料领域的应用。
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