CN105669960A - 掺锶羟基磷灰石表面接枝聚(ε-己内酯)复合材料及其制备方法 - Google Patents
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Abstract
本发明涉及了一种掺锶羟基磷灰石表面接枝聚(ε-己内酯)复合材料及其制备方法。该方法首先是利用酸碱法制备掺锶羟基磷灰石纳米粒子,并在高温下将其活化,以此为引发剂,在辛酸亚锡的催化下,引发ε-己内酯开环聚合,从而制得一种有机/无机杂化复合材料。本发明将具有良好成骨诱导活性、较高机械强度的掺锶羟基磷灰石纳米粒子,和具有较好柔韧性、可加工性、生物相容性、及药物通透性的聚(ε-己内酯),有效地融合在一起。克服了无机材料脆性大,分散性差以及单纯的聚(ε-己内酯)材料生物活性较差的缺点。在骨组织工程修复领域有着良好的发展前景。
Description
技术领域
本发明涉及一种掺锶羟基磷灰石表面接枝聚(ε-己内酯)复合材料及其制备方法。
背景技术
羟基磷灰石是人骨骼和牙齿的主要无机成分,具有优良的生物相容性,能与骨组织紧密接触,具有良好的骨传导性,并对新骨生长具有一定诱导作用,在组织工程领域被广泛应用。研究发现,羟基磷灰石(HA)中的Ca被Sr、Mg、Ti、Fe、Mn、Zn等二价金属元素取代后,可以有效改善其成骨诱导活性。
本发明提出在掺锶羟基磷灰石粒子表面接枝聚(ε-己内酯)的方法制备掺锶羟基磷灰石/聚己内酯复合材料。其中聚(ε-己内酯)材料具有良好的力学强度、加工性能、生物相容性、及药物通透性。
目前,已有通过先在HA表面接枝乳酸或低聚乳酸,然后再引发环酯单体开环聚合,同现有技术相比,本发明操作步骤少,制备方法简单。所制备的材料与以物理方式结合的无机纳米粒子/聚合物复合材料相比,具有更好的分散性,有机/无机相的界面有着更强的粘连。同时,其具有良好的生物相容性、生物可降解性和成骨诱导活性,在骨组织工程领域具有广阔应用前景。
发明内容
本发明的目的之一在于克服现有技术中存在的问题,提供一种掺锶羟基磷灰石表面接枝聚(ε-己内酯)复合材料及。
本发明的目的之二在于提供该复合材料的制备方法。
本发明通过高温活化Srx-HA表面的羟基,在辛酸亚锡的催化下,引发ε-己内酯(ε-CL)开环聚合,并通过调整反应时间来控制聚(ε-己内酯)的接枝率。具体技术方案如下:
一种掺锶羟基磷灰石表面接枝聚(ε-己内酯)复合材料,其特征在于该复合材料是以活化后的掺锶羟基磷灰石纳米粒子为引发剂,引发ε-己内酯开环聚合,得一种有机/无机杂化复合材料,其接枝率为:1%~6%;所述的掺锶羟基磷灰石纳米粒子中钙元素与锶元素的摩尔比为:0<nSr/nCa<10。
所述的复合材料的分子量分布范围在:1×105~1×106。
上述的掺锶羟基磷灰石纳米粒子的粒径分布范围在:20nm~500nm。
一种制备上述的掺锶羟基磷灰石表面接枝聚(ε-己内酯)复合材料的方法,其特征在于该方法的具体步骤为:
a.将氢氧化锶和氢氧化钙分散于去离子水中,控制n(Sr/Ca)=0~10;在90℃~100℃温度下,缓慢滴加0.10~0.20M的磷酸,磷酸浓度不易过大,控制钙和锶的摩尔数之和与磷的摩尔数的比为1.67:1;调整体系pH为10.0~11.0,真空反应24h,陈化2~3天,去离子水洗涤,得到掺锶羟基磷灰石纳米粒子Srx-HA,x=nSr/n(Ca+Sr);
b.将步骤a所得Srx-HA在100℃~120℃活化2h后;
c.将步骤b所得0.1~1gSrx-HA和5~10g精馏过的ε-己内酯单体于甲苯中,再加入0.88mL0.1~0.2molL-1的Sn(Oct)2的甲苯溶液作催化;于密闭容器中,在惰性气氛保护下,于100°C~120°C下反应3~24h;反应完毕后,所得产物用乙醚沉降,冷冻干燥,即得掺锶羟基磷灰石表面接枝聚(ε-己内酯)复合材料。
所述的掺锶羟基磷灰石表面接枝聚(ε-己内酯)复合材料的接枝率为所接枝上的聚合物对整个无机/聚合物粒子的质量比。
本发提供的Srx-HA-g-PCL复合材料可有效改善Srx-HA无机材料易团聚、脆性大、韧性不足等缺陷,同时还改善无机材料表面性能,增强其界面粘附力;同时,Srx-HA纳米粒子可以提高单纯聚(ε-己内酯)材料的生物活性。该材料是一种颇具应用前景的骨修复及替代材料,在组织工程领域具有很大的应用价值。
本发明提出在掺锶羟基磷灰石粒子表面接枝聚(ε-己内酯)的方法制备掺锶羟基磷灰石/聚己内酯复合材料。其中聚(ε-己内酯)材料具有良好的力学强度、加工性能、生物相容性、及药物通透性。
目前,已有通过先在HA表面接枝乳酸或低聚乳酸,然后再引发环酯单体开环聚合,同现有技术相比,本发明操作步骤少,制备方法简单。所制备的材料与以物理方式结合的无机纳米粒子/聚合物复合材料相比,具有更好的分散性,有机/无机相的界面有着更强的粘连。同时,其具有良好的生物相容性、生物可降解性和成骨诱导活性,在骨组织工程领域具有广阔应用前景。
具体实施方式
下面实例进一步说明本发明,但本发明不仅限于此。
实施例一:
将氢氧化锶和氢氧化钙分散于去离子水中,控制n(Sr/Ca)=1:9。并将其加热至90℃~100℃后,缓慢滴加0.10~0.20M的稀磷酸,控制n(Ca+Sr)/nP=1.67。待磷酸滴加完后,用氨水调整体系pH为10.0~11.0,真空反应24h,陈化2~3d,去离子水洗涤2~3次,冷冻干燥,得到Sr10-HA纳米粒子。
取一带有磁子的封闭安瓶,用煤气焰烘烤除水后,加入2g已在100℃~120℃烘箱中活化2h的Sr10-HA,用注射器取2~5g精馏过的ε-CL单体加入安瓶中,再依次加入50mL精制甲苯、和0.88mL0.1~0.2molL-1的Sn(Oct)2的甲苯溶液,在N2气氛下,于100~120°C油浴中反应3~4h。反应完毕后,所得产物用乙醚沉降,冷冻干燥,即得Sr10-HA-g-PCL复合材料,其接枝率为5%。
实施例二:
将氢氧化锶和氢氧化钙分散于去离子水中,控制n(Sr/Ca)=1:9。并将其加热至90℃~100℃后,缓慢滴加0.10~0.20M的稀磷酸,控制n(Ca+Sr)/nP=1.67。待磷酸滴加完后,用氨水调整体系pH为10.0~11.0,真空反应24h,陈化2~3d,去离子水洗涤2~3次,冷冻干燥,得到Sr10-HA纳米粒子。
取一带有磁子的封闭安瓶,用煤气焰烘烤除水后,加入2g已在100℃~120℃烘箱中活化2h的Sr10-HA,用注射器取2~5g精馏过的ε-CL单体加入安瓶中,再依次加入50mL精制甲苯、和0.88mL0.1~0.2molL-1的Sn(Oct)2的甲苯溶液,在N2气氛下,于100~120°C油浴中反应6~8h。反应完毕后,所得产物用乙醚沉降,冷冻干燥,即得Sr10-HA-g-PCL复合材料,其接枝率为6%。
实施例三:
将氢氧化锶和氢氧化钙分散于去离子水中,控制n(Sr/Ca)=1:1。并将其加热至90℃~100℃后,缓慢滴加0.10~0.20M的稀磷酸,控制n(Ca+Sr)/nP=1.67。待磷酸滴加完后,用氨水调整体系pH为10.0~11.0,真空反应24h,陈化2~3d,去离子水洗涤2~3次,冷冻干燥,得到Sr50-HA纳米粒子。
取一带有磁子的封闭安瓶,用煤气焰烘烤除水后,加入2g已在100℃~120℃烘箱中活化2h的Sr50-HA,用注射器取2~5g精馏过的ε-CL单体加入安瓶中,再依次加入50mL精制甲苯、和0.88mL0.1~0.2molL-1的Sn(Oct)2的甲苯溶液,在N2气氛下,于100~120°C油浴中反应3~4h。反应完毕后,所得产物用乙醚沉降,冷冻干燥,即得Sr50-HA-g-PCL复合材料,其接枝率为5%。
实施例四:
将氢氧化锶和氢氧化钙分散于去离子水中,控制n(Sr/Ca)=1:1。并将其加热至90℃~100℃后,缓慢滴加0.10~0.20M的稀磷酸,控制n(Ca+Sr)/nP=1.67。待磷酸滴加完后,用氨水调整体系pH为10.0~11.0,真空反应24h,陈化2~3d,去离子水洗涤2~3次,冷冻干燥,得到Sr50-HA纳米粒子。
取一带有磁子的封闭安瓶,用煤气焰烘烤除水后,加入0.56g已在100℃~120℃烘箱中活化2h的Sr50-HA,用注射器取2~5g精馏过的ε-CL单体加入安瓶中,再依次加入50mL精制甲苯、和0.88mL0.1~0.2molL-1的Sn(Oct)2的甲苯溶液,在N2气氛下,于100~120°C油浴中反应6~8h。反应完毕后,所得产物用乙醚沉降,冷冻干燥,即得Sr50-HA-g-PCL复合材料,其接枝率为6%。
以上所述仅为本发明的较佳实施比例,并不用以限制本发明,凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等,均应包含在本发明的保护范围之内。
Claims (4)
1.一种掺锶羟基磷灰石表面接枝聚(ε-己内酯)复合材料,其特征在于该复合材料是以活化后的掺锶羟基磷灰石纳米粒子为引发剂,引发ε-己内酯开环聚合,得一种有机/无机杂化复合材料,其接枝率为:1%~6%;所述的掺锶羟基磷灰石纳米粒子中钙元素与锶元素的摩尔比为:0<nSr/nCa<10。
2.根据权利要求1所述的掺锶羟基磷灰石表面接枝聚(ε-己内酯)复合材料,其特征在于该复合材料的分子量分布范围在:1×105~1×106。
3.根据权利要求1所述的掺锶羟基磷灰石表面接枝聚(ε-己内酯)复合材料,其特征在于所述的掺锶羟基磷灰石纳米粒子的粒径分布范围在:20nm~500nm。
4.一种制备根据权利要求1、2或3中所述的掺锶羟基磷灰石表面接枝聚(ε-己内酯)复合材料的方法,其特征在于该方法的具体步骤为:
a.将氢氧化锶和氢氧化钙分散于去离子水中,控制n(Sr/Ca)=0~10;在90℃~100℃温度下,缓慢滴加0.10~0.20M的磷酸,磷酸浓度不易过大,控制钙和锶的摩尔数之和与磷的摩尔数的比为1.67:1;调整体系pH为10.0~11.0,真空反应24h,陈化2~3天,去离子水洗涤,得到掺锶羟基磷灰石纳米粒子Srx-HA,x=nSr/n(Ca+Sr);
b.将步骤a所得Srx-HA在100℃~120℃活化2h后;
c.将步骤b所得0.1~1gSrx-HA和5~10g精馏过的ε-己内酯单体于甲苯中,再加入0.88mL0.1~0.2molL-1的Sn(Oct)2的甲苯溶液作催化;于密闭容器中,在惰性气氛保护下,于100°C~120°C下反应3~24h;反应完毕后,所得产物用乙醚沉降,冷冻干燥,即得掺锶羟基磷灰石表面接枝聚(ε-己内酯)复合材料。
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CN103834041A (zh) * | 2014-02-21 | 2014-06-04 | 重庆医药高等专科学校 | 一种MGF-Ct24E功能化聚乳酸仿生骨基质材料及其制备方法 |
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CN1544524A (zh) * | 2003-11-17 | 2004-11-10 | 中国科学院长春应用化学研究所 | 羟基磷灰石生物降解脂肪族聚酯复合材料的制备方法 |
CN103319696A (zh) * | 2012-03-23 | 2013-09-25 | 中国科学院化学研究所 | 一种羟基磷灰石/可生物降解聚酯复合材料及其制备方法 |
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