CN108083248A - 一种高分散性纳米磷灰石的制备方法 - Google Patents

一种高分散性纳米磷灰石的制备方法 Download PDF

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CN108083248A
CN108083248A CN201810061333.3A CN201810061333A CN108083248A CN 108083248 A CN108083248 A CN 108083248A CN 201810061333 A CN201810061333 A CN 201810061333A CN 108083248 A CN108083248 A CN 108083248A
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蒋柳云
丁豪杰
马兵利
苏胜培
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Abstract

本发明公开了一种高分散性纳米磷灰石的制备方法。该高分散性纳米磷灰石是指将羧基化环糊精与钙盐反应，然后添加无机磷源，调pH值在10左右，在30℃~90℃下加热搅拌反应3~6小时后，静置过夜，倾去上层清液，水洗至pH值到7左右，用无水乙醇洗2~3次，从而制备一种高分散性的纳米磷灰石。本发明制得的纳米磷灰石不仅在亲水性溶剂中具有很好的分散性，同时还能在二氯甲烷等疏水性溶液中保持高度分散性，因而有望用于与不同聚合物以高含量复合制得高骨传导性的复合材料用做骨科材料。

Description

一种高分散性纳米磷灰石的制备方法
技术领域
本发明涉及一种高分散性纳米磷灰石的制备方法，属于生物医用材料领域。
背景技术
合成的纳米羟基磷灰石[Ca10(PO4)6(OH)2, n-HA]，因其成分与结构与人骨的无机组分相似，因而常用于高聚物填料，以赋予高聚物骨传导性及发挥其纳米增强效应，从而获得理想的复合材料用于骨修复、骨折、椎间融合器等大部分骨科材料，这已成为骨科材料中研究的重点。但研究表明，n-HA无机纳米粒子因其固有的易团聚特性，尤其是其表面亲水性，因而很难在疏水性溶剂中分散，以致难以与疏水性高聚物复合，已成为骨科材料研究中亟待解决的难题。
为解决n-HA无机粒子与疏水性高聚物复合时的界面结合问题，国内外研究人员对n-HA进行了大量表面接枝改性研究，但在n-HA接枝前纳米粒子大部分可能已经团聚，以致改性效果甚微，从而分散性未能得到明显提高，且接枝过程繁琐、毒性大、成本高。而在n-HA制备过程中引入一些大分子有机物可有效提高其分散性。
申请人在前期研究中关注到环糊精(Cyclodextrin，简称CD)是一系列环状低聚糖大分子的总称，具有独特的腔内疏水，腔外亲水的圆台式结构，是骨科中具有功能化的材料。因而提出了采用磷酸化环糊精作为磷源制备功能性纳米磷灰石的新思想，即将磷酸化环糊精做为辅助磷源，再依次加入钙源和无机磷源，保持钙和磷的摩尔比为1.67，获得的新型纳米磷灰石其分散性有所提高，并申请了相关专利（公开号CN106924819A）。但采用的磷酸化环糊精在水中溶解度较低，需在N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲基亚砜等有机溶剂中才能溶解，使实验成本提高，同时也给环境带来污染。而羧甲基环糊精(Carboxymethyl Cyclodextrin，简称CM-CD)在环糊精上引入了羧基，因而在水中溶解度比环糊精大大提高，同时利用羧甲基环糊精上的羧基与钙结合，再与磷酸盐结合而获得特殊结构的纳米磷灰石，因此若在HA制备过程中将羧甲基环糊精引入，则有望提高其分散性，以用于与不同聚合物以高含量复合制得高骨传导性的复合材料用于骨科材料。
发明内容
本发明提供了一种羧甲基环糊精掺杂的高分散性纳米磷灰石的制备方法，该方法制备的新型纳米磷灰石不仅在水溶液中具有很高的分散性，同时还能在二氯甲烷等疏水性溶液中保持高度分散，因而可用于与不同聚合物以高含量复合制得高骨传导性的复合材料用于骨科材料。
一种高分散性纳米磷灰石的制备方法，包括如下步骤：
将羧甲基环糊精溶于水，浓度为30~50g/100ml，然后按不同比例添加无机钙源水溶液，再添加无机磷盐，保持钙磷摩尔比为1.67，调pH值在10~12之间，在30~90℃下搅拌反应3~6小时后，静置过夜，洗涤，待用。
本发明中，利用羧甲基化环糊精制备杂化纳米磷灰石，其特征是指α、β、γ型环糊精中的一种羧基化环糊精；
本发明中羧甲基环糊精与钙盐反应，然后添加磷源，其钙盐特征是指硝酸钙、氯化钙等可溶性盐，磷源是指磷酸钠、磷酸二氢铵等可溶性盐，保持溶液中总的钙与磷的摩尔比为1.67；
本发明中羧甲基环糊精与钙盐反应，其两者摩尔比为3:10~10:3。
本发明提供的高分散性纳米磷灰石的制备方法优越性在于：
（1）从材料的性能来说，与现有的n-HA相比，本发明制备的纳米磷灰石结构中引入了羧甲基环糊精大分子，赋予了其空间位阻作用而实现高分散性，还可赋予其环糊精结构的两亲性，使其与各类亲疏水性高聚物复合都有良好的界面结合性，解决其与疏水性高聚物复合的难题。
（2）本发明各种原材料易得，可以自制或市场上购买，制备步骤简单，反应条件温和，所用试剂均对环境无污染，且反应时间短，适合于大规模生产。
（3）本发明制备的高分散性纳米磷灰石因带有羧甲基环糊精结构，因而结晶度明显比n-HA具有更低，从而可提高其降解性，扩大应用范围，以致与亲疏水性各类高聚物复合所得的复合材料在骨填充颗粒、骨组织工程支架材料、引导骨组织再生膜、载药材料等多种骨科领域有很大的应用前景。
附图说明
图1为下述实施例的部分粉末在二氯甲烷中的分散照片及XRD谱图。(a)和(a) 是传统法制备的n-HA, (b)和(b)羧基化β-环糊精与n-HA共混法获得的纳米磷灰石，(c)和(c) 引入β-环糊精的与n-HA共沉淀法获得的纳米磷灰石, (d)和(d) 引入羧基化β-环糊精的与n-HA共沉淀法获得的纳米磷灰石。
具体实施方式
实施例1：取17.36 g 羧基化β-环糊精溶于200 ml水，加入8.86 g四水硝酸钙溶于100 ml水，搅拌3小时后，再加入十二水磷酸钠8.55 g溶于100 ml水，缓慢滴加于上述溶液中，用10 wt%的氢氧化钠调pH值为10左右，70 ℃加热搅拌4小时，静置48小时后，用去离子水洗涤5遍，再用乙醇洗涤3遍，烘干后备用。
实施例2：取5.79 g 羧基化β-环糊精溶于300 ml水，加入26.58 g四水硝酸钙溶于300 ml水，搅拌2小时后，再加入十二水磷酸钠25.63 g溶于150 ml水，缓慢滴加于上述溶液中，用15 wt%的氢氧化钠调pH值为12左右，80 ℃加热搅拌6小时，静置48小时后，用去离子水洗涤5遍，再用乙醇洗涤3遍，烘干后备用。
实施例3：取7.74 g 羧基化α-环糊精溶于100 ml水，加入和17.70 g四水硝酸钙溶于200 ml水，搅拌3小时后，再加入十二水磷酸钠17.07 g溶于50 ml水，缓慢滴加于上述溶液中，用10 wt%的氢氧化钠调pH值为10左右，60 ℃加热搅拌4小时，静置48小时后，用去离子水洗涤5遍，再用乙醇洗涤3遍，烘干后备用。
实施例4：取9.15 g羧基化γ-环糊精溶于250 ml水，加入和15.93 g四水硝酸钙溶于180 ml水，搅拌2小时后，再加入十二水磷酸钠15.39 g溶于120 ml水，缓慢滴加于上述溶液中，用12 wt%的氢氧化钠调pH值为10左右，60 ℃加热搅拌4小时，静置48小时后，用去离子水洗涤5遍，再用乙醇洗涤3遍，烘干后备用。
对比实施例1：取11.81 g四水硝酸钙溶于50 ml水，搅拌2小时后，再加入十二水磷酸钠11.38 g溶于50 ml水，缓慢滴加于上述溶液中，用10 wt%的氢氧化钠调pH值为10左右，70 ℃加热搅拌4小时，静置48小时后，用去离子水洗涤5遍，再用乙醇洗涤3遍，烘干后备用。
对比实施例2：取16.14 g β-磷酸环糊精溶于400 ml水，加入21.26 g四水硝酸钙溶于300 ml水，搅拌2小时后，再加入十二水磷酸钠21.24 g溶于150 ml水，缓慢滴加于上述溶液中，用15 wt%的氢氧化钠调pH值为10左右，70 ℃加热搅拌6小时，静置48小时后，用去离子水洗涤5遍，再用乙醇洗涤3遍，烘干后备用。
对比实施例3：取16.14 g β-磷酸环糊精溶于400 ml水，将9.04 g羟基磷灰石加水200 ml分散后缓慢滴加于上述溶液中，70 ℃加热搅拌6小时，静置48小时后，用去离子水洗涤5遍，再用乙醇洗涤3遍，烘干后备用。
附图1为上述实施例的部分粉末在二氯甲烷中的分散照片及其XRD谱图。

Claims (3)

1.一种高分散性纳米磷灰石的制备方法，其特征是指将羧甲基环糊精与钙盐反应，然后添加磷源，保持钙与磷的摩尔比为1.67，调pH值，在一定温度下搅拌反应一定时间后，静置过夜，洗涤，待用。
2.按照权利要求1所述的羧基化环糊精，其特征是指α、β、γ型环糊精中的任一种。
3.按照权利要求1所述的羧甲基环糊精与钙盐反应，其两者摩尔比为3:10~10:3。
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