CN109535314A - 一种疏水性纳凝胶及其制备方法 - Google Patents
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Abstract
本发明公开了一种疏水性纳凝胶及其制备方法。所述的疏水性纳凝胶,以聚甲基丙烯酸缩水甘油酯为骨架,粒径为10~250 nm,Zeta电位为‑40~‑50 mV,分散指数为0.1~0.2,具有如式(I)所示疏水功能的甘油酯基团和高活性的环氧基团结构:
Description
技术领域
本发明涉及纳米材料领域,具体涉及一种疏水性纳凝胶及其制备方法。
背景技术
纳凝胶是指高分子链通过化学或者物理作用相互交联形成的具有三维网状结构且粒径小于1000 nm的凝胶颗粒。水和凝胶网络之间存在亲和性,水能够以键合水、束缚水和自由水等形式存在于纳凝胶网络中而失去流动性,因此纳凝胶在水中具有溶胀却不溶解的特性且能够保持一定的稳定状态。
纳凝胶具有水凝胶和纳米材料的双重特性,尺寸小,比表面积大,部分纳凝胶能够对周围环境的变化迅速响应,例如对pH、温度和光等具有环境响应性,利用纳凝胶与生物活性物质的刺激响应现象可以检测相关物质的浓度及其变化。同时纳凝胶也具有良好的载药能力和生物相容性,纳凝胶与生物医学的结合,促进了临床医学诊断技术和治疗水平的提高,它作为载体可以准确地将药物运输到靶细胞来治疗疾病,提高药物的利用率,已经成为医药界的研究热点。
近年来,纳凝胶的研究方向主要集中在亲水和两亲性方面,对于疏水性纳凝胶的制备及机理研究较少。
发明内容
针对现有技术存在的上述技术问题,本发明的目的在于提供一种疏水性纳凝胶及其制备方法。
所述的一种疏水性纳凝胶,其特征在于所述的疏水性纳凝胶粒径的骨架基质为聚甲基丙烯酸缩水甘油酯,疏水性纳凝胶中含有如式(Ⅰ)所示具有疏水功能的甘油酯基团和高活性环氧基团结构:
(I)
式(Ⅰ)中,m、n均为大于零的整数。
所述的疏水性纳凝胶,其特征在于所述疏水性纳凝胶的粒径为10~250 nm,Zeta电位-40~-50 mV,分散性指数0.1~0.2。
所述的疏水性纳凝胶的制备方法,其特征在于将甲基丙烯酸缩水甘油酯、二甲基丙烯酸乙二醇酯、十二烷基硫酸钠和去离子水超声混合均匀,形成水包油型乳液,然后加入过硫酸铵和N,N,N',N'-四甲基乙二胺,加热下静置反应,反应结束后反应液冷却至室温,制得含有聚甲基丙烯酸缩水甘油酯的纳米凝胶,即为所述疏水性纳凝胶。
所述的疏水性纳凝胶的制备方法,其特征在于甲基丙烯酸缩水甘油酯、二甲基丙烯酸乙二醇酯、十二烷基硫酸钠和去离子水的混合液中,甲基丙烯酸缩水甘油酯的质量分数为0.59%~10%,二甲基丙烯酸乙二醇酯的质量分数为0%~0.41%,十二烷基硫酸钠的质量分数为0.5%~4%。
所述的疏水性纳凝胶的制备方法,其特征在于甲基丙烯酸缩水甘油酯和二甲基丙烯酸乙二醇酯两者质量之和记为聚合单体的质量,过硫酸铵的质量为聚合单体质量的0.6%~3%,N,N,N',N'-四甲基乙二胺的质量为聚合单体质量的1.2%~6%。
所述的疏水性纳凝胶的制备方法,其特征在于,反应温度为50~70℃,反应时间为3~10 min。
通过采用上述技术,本发明具有如下有益效果:
1)本发明提供的新型疏水性纳凝胶,兼具水凝胶和纳米材料的双重特性,尺寸小,比表面积大,分散稳定,分布均匀,可以与其它生化分离介质相互结合,增加介质内部吸附点位,提高吸附量;同时,采用聚甲基丙烯酸缩水甘油酯等生物相容性好的聚合物材料,安全性高。
2)本发明提供的新型疏水性纳凝胶具有疏水性基团,可以负载一些难溶于水的药物,可用于缓释给药。此外,甲基丙烯酸缩水甘油酯是含有环氧基的疏水单体,通过与疏水交联剂二甲基丙烯酸乙二醇酯反应生成疏水性纳凝胶,该纳凝胶含有疏水和高活性的基团,易于修饰后转变成两亲性或亲水性凝胶基质;含有高反应性的环氧基,可以简单快速地利用环氧基经反应或接枝得到羧基、羟基和氨基等亲水基团,使该纳凝胶具有变成两亲性或亲水性的潜力,在生物医药和生物分离等领域具有较大前景。
3)本发明提供的新型疏水性纳凝胶,其制备方法采用微乳直接合成纳凝胶,具有操作简单,反应条件温和,所得纳凝胶稳定等优点。
具体实施方式
下面结合具体的实施例对本发明进行进一步描述,但本发明的保护范围并不仅限于此:
以下实施例中,%均指质量百分数的单位。
实施例1:
以所有的原料总量为100%计,将含有0.59%甲基丙烯酸缩水甘油酯、0.41%二甲基丙烯酸乙二醇酯、0.5%十二烷基硫酸钠和98.41%去离子水的混合液在玻璃瓶中超声混合均匀,形成水包油型乳液,放置到70℃的水浴温度下,同步加入质量为甲基丙烯酸缩水甘油酯和二甲基丙烯酸乙二醇酯两者总质量3%的过硫酸铵和6%的N,N,N',N'-四甲基乙二胺催化剂,70℃下继续静置反应8 min,反应结束后迅速冷却至室温,得到聚甲基丙烯酸缩水甘油酯纳米凝胶粗品,将制得的聚甲基丙烯酸缩水甘油酯纳米凝胶粗品用Malvern ZS90粒度分析仪对纳凝胶粒径进行测试,得到的纳米凝胶粒径为10~190 nm,平均粒径约为41 nm,Zeta电位约为-40 mV,分散指数约为0.2,本发明所得的粗品可直接作为中间原料进行其它反应;本发明也可将制得的粗品进行后处理得到精品,具体的后处理过程如下:往纳凝胶溶液中加入无水乙醇,纳凝胶沉淀析出,再用去离子水洗涤沉淀物,去除残留的催化剂和未反应的单体,经冷冻干燥后可得到纯净的纳米凝胶,以后实施例中的后处理方法与实施例1相同。
实施例2:
以所有的原料总量为100%计,将含有2.8%甲基丙烯酸缩水甘油酯、0.2%二甲基丙烯酸乙二醇酯、2%十二烷基硫酸钠和94.73%去离子水的混合液在玻璃瓶中超声混合均匀,形成水包油型乳液,放置到50℃的水浴温度下,同步加入质量为甲基丙烯酸缩水甘油酯和二甲基丙烯酸乙二醇酯总量3%的过硫酸铵和6%的N,N,N',N'-四甲基乙二胺催化剂,50℃下继续静置反应10 min,反应结束后迅速冷却至室温,得到聚甲基丙烯酸缩水甘油酯纳米凝胶。将制得的聚甲基丙烯酸缩水甘油酯纳米凝胶用Malvern ZS90粒度分析仪对纳米凝胶粒径进行测试。得到的纳凝胶粒径为40~250 nm,平均粒径约为90 nm,Zeta电位-49 mV,分散指数0.17。
实施例3:
以所有的原料总量为100%计,将含有4.93%甲基丙烯酸缩水甘油酯、0.07%二甲基丙烯酸乙二醇酯、2.5%十二烷基硫酸钠和92.41%去离子水的混合液在玻璃瓶中超声混合均匀,形成水包油型乳液,放置到70℃的水浴温度下,同步加入质量为甲基丙烯酸缩水甘油酯和二甲基丙烯酸乙二醇酯总量0.6%的过硫酸铵和1.2%的N,N,N',N'-四甲基乙二胺催化剂,70℃下继续静置反应8 min,反应结束后迅速冷却至室温,得到聚甲基丙烯酸缩水甘油酯纳米凝胶。将制得的聚甲基丙烯酸缩水甘油酯纳米凝胶用Malvern ZS90粒度分析仪对纳米凝胶粒径进行测试。得到的纳凝胶粒径为30~220 nm,平均粒径约70 nm,Zeta电位约为-40 mV,分散指数约为0.1。
实施例4:
以所有的原料总量为100%计,将含有6.98%甲基丙烯酸缩水甘油酯、0.02%二甲基丙烯酸乙二醇酯、1%十二烷基硫酸钠和91.82%去离子水的混合液在玻璃瓶中超声混合均匀,形成水包油型乳液,放置到70℃的水浴温度下,同步加入质量为甲基丙烯酸缩水甘油酯和二甲基丙烯酸乙二醇酯总量0.86%的过硫酸铵和1.71%的N,N,N',N'-四甲基乙二胺催化剂,70℃下继续静置反应3 min,反应结束后迅速冷却至室温,得到聚甲基丙烯酸缩水甘油酯纳米凝胶。将制得的聚甲基丙烯酸缩水甘油酯纳米凝胶用Malvern ZS90粒度分析仪对纳米凝胶粒径进行测试。得到的纳凝胶粒径为10~220 nm,平均粒径为50 nm,Zeta电位-45 mV,分散指数0.2。
实施例5:
以所有的原料总量为100%计,将含有10%甲基丙烯酸缩水甘油酯、4%十二烷基硫酸钠和85.82%去离子水的混合液在玻璃瓶中超声混合均匀,形成水包油型乳液,放置到70℃的水浴温度下,同步加入质量为甲基丙烯酸缩水甘油酯和二甲基丙烯酸乙二醇酯总量0.6%的过硫酸铵和1.2%的N,N,N',N'-四甲基乙二胺催化剂,70℃下继续静置反应8 min,反应结束后迅速冷却至室温,得到聚甲基丙烯酸缩水甘油酯纳米凝胶。将制得的聚甲基丙烯酸缩水甘油酯纳米凝胶用Malvern ZS90粒度分析仪对纳凝胶粒径进行测试。得到的纳凝胶粒径为30~190 nm,平均粒径约为76 nm,Zeta电位-50 mV,分散指数0.12。
Claims (6)
1.一种疏水性纳凝胶,其特征在于所述的疏水性纳凝胶粒径的骨架基质为聚甲基丙烯酸缩水甘油酯,疏水性纳凝胶中含有如式(Ⅰ)所示具有疏水功能的甘油酯基团和高活性环氧基团结构:
(I)
式(Ⅰ)中,m、n均为大于零的整数。
2.根据权利要求1所述的疏水性纳凝胶,其特征在于所述疏水性纳凝胶的粒径为10~250 nm,Zeta电位-40~-50 mV,分散性指数0.1~0.2。
3.根据权利要求1所述的疏水性纳凝胶的制备方法,其特征在于将甲基丙烯酸缩水甘油酯、二甲基丙烯酸乙二醇酯、十二烷基硫酸钠和去离子水超声混合均匀,形成水包油型乳液,然后加入过硫酸铵和N,N,N',N'-四甲基乙二胺,加热下静置反应,反应结束后反应液冷却至室温,制得含有聚甲基丙烯酸缩水甘油酯的纳米凝胶,即为所述疏水性纳凝胶。
4.根据权利要求3所述的疏水性纳凝胶的制备方法,其特征在于甲基丙烯酸缩水甘油酯、二甲基丙烯酸乙二醇酯、十二烷基硫酸钠和去离子水的混合液中,甲基丙烯酸缩水甘油酯的质量分数为0.59%~10%,二甲基丙烯酸乙二醇酯的质量分数为0%~0.41%,十二烷基硫酸钠的质量分数为0.5%~4%。
5.根据权利要求3所述的疏水性纳凝胶的制备方法,其特征在于甲基丙烯酸缩水甘油酯和二甲基丙烯酸乙二醇酯两者质量之和记为聚合单体的质量,过硫酸铵的质量为聚合单体质量的0.6%~3%,N,N,N',N'-四甲基乙二胺的质量为聚合单体质量的1.2%~6%。
6.根据权利要求3所述的疏水性纳凝胶的制备方法,其特征在于,反应温度为50~70℃,反应时间为3~10 min。
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4622367A (en) * | 1984-12-12 | 1986-11-11 | Ceskoslovenska Akademie Ved | X-ray contrast spherical hydrogel particles based on polymer and copolymers of acrylates and methacrylates and the method for preparation thereof |
EP2143482A1 (en) * | 2003-02-19 | 2010-01-13 | Natrix Separations Inc. | Composite materials comprising supported porous gels |
CN103194800A (zh) * | 2013-02-28 | 2013-07-10 | 吉林大学 | 光子禁带大范围可调节的聚合物光子晶体的制备方法 |
CN103436965A (zh) * | 2013-07-13 | 2013-12-11 | 吉林大学 | 光子禁带可调节及呈现图案化颜色显示的聚合物光子晶体的制备方法 |
-
2018
- 2018-11-23 CN CN201811409173.3A patent/CN109535314B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4622367A (en) * | 1984-12-12 | 1986-11-11 | Ceskoslovenska Akademie Ved | X-ray contrast spherical hydrogel particles based on polymer and copolymers of acrylates and methacrylates and the method for preparation thereof |
EP2143482A1 (en) * | 2003-02-19 | 2010-01-13 | Natrix Separations Inc. | Composite materials comprising supported porous gels |
EP2143481A1 (en) * | 2003-02-19 | 2010-01-13 | Natrix Separations Inc. | Composite materials comprising supported porous gels |
CN103194800A (zh) * | 2013-02-28 | 2013-07-10 | 吉林大学 | 光子禁带大范围可调节的聚合物光子晶体的制备方法 |
CN103436965A (zh) * | 2013-07-13 | 2013-12-11 | 吉林大学 | 光子禁带可调节及呈现图案化颜色显示的聚合物光子晶体的制备方法 |
Non-Patent Citations (2)
Title |
---|
CHANTAL PAQUET, ETAL.: "Nanobeads Highly Loaded with Superparamagnetic Nanoparticles Prepared by Emulsification and Seeded-Emulsion Polymerization", 《LANGMUIR》 * |
RENWEI WANG, ET AL.: "Preparation of Uniform Poly(glycidyl methacrylate) Porous Microspheres by Membrane Emulsification Polymerization Technology", 《JOURNAL OF APPLIED POLYMER SCIENCE》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111056646A (zh) * | 2019-10-21 | 2020-04-24 | 浙江工业大学 | 一种可漂浮性颗粒的制备方法 |
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