CN107952109A - 一种注射型骨填充材料及制备方法 - Google Patents
一种注射型骨填充材料及制备方法 Download PDFInfo
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- MMXZSJMASHPLLR-UHFFFAOYSA-N pyrroloquinoline quinone Chemical compound C12=C(C(O)=O)C=C(C(O)=O)N=C2C(=O)C(=O)C2=C1NC(C(=O)O)=C2 MMXZSJMASHPLLR-UHFFFAOYSA-N 0.000 claims abstract description 28
- 229910052712 strontium Inorganic materials 0.000 claims abstract description 25
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000001913 cellulose Substances 0.000 claims abstract description 18
- 229920002678 cellulose Polymers 0.000 claims abstract description 18
- GBNXLQPMFAUCOI-UHFFFAOYSA-H tetracalcium;oxygen(2-);diphosphate Chemical compound [O-2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GBNXLQPMFAUCOI-UHFFFAOYSA-H 0.000 claims abstract description 18
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims abstract description 17
- 235000019700 dicalcium phosphate Nutrition 0.000 claims abstract description 17
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- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 claims abstract description 3
- 239000001506 calcium phosphate Substances 0.000 claims description 39
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 39
- 235000011010 calcium phosphates Nutrition 0.000 claims description 39
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 39
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Abstract
本发明涉及一种注射型骨填充材料及制备方法，由质量分数为20～50％的多孔陶瓷颗粒与50～80％的硫酸钙水泥组成。通过溶液喷雾振动造粒，以磷酸四钙、磷酸氢钙为原料，以锶磷灰石为籽晶，控制反应的温度、湿度和时间，生成锶掺杂磷灰石，再经烧结造孔及提升锶磷灰石的结晶度及转变晶相，制备粒径可控的锶掺杂双相陶瓷，辅以硫酸钙水泥，纤维素的加入增强了骨填充材料抗水溃散性、粘结性及韧性，采用微创注射到骨缺损部位，增强骨填充材料的力学性能，避免了开放手术操作，并随着添加的吡咯喹啉醌释放增强机体的免疫力，提升骨填充材料的诱导性，加速骨缺损的修复。注射型骨填充材料抗压强度均在10MPa以上，满足人体松质骨修复的需要。
Description
技术领域
本发明涉及一种注射型骨填充材料及制备方法，主要用于生物医用材料等领域。
背景技术
骨缺损是临床骨科最常见的病症之一，可由感染、外伤、肿瘤和先天性疾病等造成，大部分不能自愈而需进行骨移植。随着人口老龄化和各种创伤的增多，对生物医学材料尤其是骨移植材料的需求也持续增长。很多天然的和合成的材料和组合物已被用于骨缺损的治疗。
自体骨长久以来一直被认为是最有效的骨修复材料，因为它同时具有骨诱导性和非免疫原性。大量研究表明，同种或异种骨移植的修复程度与移植骨大小有关，颗粒骨移植的临床成功应用效果及成功率均高于大的块状骨移植。这主要是因为颗粒骨比块状骨具有更佳的成骨效果，但单纯颗粒骨移植结构松散，不易成型，单独使用容易引发颗粒游走、移位、压迫神经等并发症，影响其骨修复能力和效果，且自体骨来源不足、术中失血增多及子术并发症等不利因素，限制了临床上的应用。
人工骨修复是目前治疗骨缺损较为理想的方法。对于临床上大量存在的不规则骨缺损，传统骨修复材料需在休外预制成型，经过于术切开后植入体内，病人需承受手术创伤，这种方式创伤较大，且不能完全充填骨缺损。近年来，伴随着微创外科的发展，可注射自固化材料的应用克服了这个问题。在精确手术定位下，注射材料只需微小的创伤即可到达骨缺损部位，在一定时间里固化并达到合适的机械强度，刺激新骨生成或为成骨细胞提供良好的支架，自身则在缺损修复过程中逐渐降解。
磷酸钙骨水泥与硫酸钙骨水泥及两者的结合作为骨修复材料已被广泛应用于临床治疗，并取得了一定的效果，但以硫酸钙水泥承载磷酸钙烧结的多孔陶瓷颗粒还未见有相关研究，磷酸钙烧结的多孔陶瓷颗粒成分与人体骨成分类似，以多孔陶瓷颗粒替代自体骨颗粒，使用硫酸钙水泥承载多孔陶瓷颗粒微创注射到缺损部位，加速骨缺损的修复。本发明采用喷雾振动造粒的方法制备陶瓷基础材料，经喷雾造粒、高温烧结成型，制备多孔陶瓷颗粒，辅以硫酸钙水泥，制备可注射型含多孔陶瓷的骨填充材料，硫酸钙固化后增加填充材料的力学性能，纤维素及吡咯喹啉醌的加入，增强材料的抗水溃散性、注射性及韧性，加速成骨细胞的分化，使成骨速率与材料的降解速率匹配，完成缺损的修复。
发明内容
本发明的目的在于提供一种注射型骨填充材料，并提供一种注射型骨填充材料的制备方法。该骨填充材料由多孔陶瓷颗粒及硫酸钙水泥组成。
注射型骨填充材料的具体组成与质量分数为20～50％的多孔陶瓷颗粒与50～80％的硫酸钙水泥组成。
多孔陶瓷颗粒为锶掺杂双相陶瓷(Sr-HA/Sr-TCP)；硫酸钙水泥由粉液两部分组成，粉体为硫酸钙粉体，液体为含0.5～5％吡咯喹啉醌的0.5～10％的纤维素溶液。
本发明的注射型骨填充材料的制备按照以下步骤：
(1)多孔陶瓷颗粒的制备：将30～80％质量分数的磷酸钙与20～70％质量分数的PVA颗粒混合均匀，通过喷雾PVA溶液振动造粒制备磷酸钙/PVA复合颗粒，其中，PVA颗粒粒径为200～350μm；
将制备的磷酸钙/PVA复合颗粒，经反应24～72h，转移到烧结炉中，烧结温度为350～1250℃，烧结时间为3～36h，室温冷却，得到多孔陶瓷颗粒，其粒径为500～2000μm，孔径为100～300μm；
(2)硫酸钙水泥的制备：按照粉液质量比3:2将硫酸钙粉体和含0.5～5％吡咯喹啉醌的0.5～10％的纤维素溶液混合均匀，得到硫酸钙水泥；
(3)骨填充材料的制备：将占骨填充材料质量分数为20～50％的多孔陶瓷颗粒推入到占骨填充材料质量分数为50～80％的硫酸钙水泥中，得到注射型骨填充材料，注射到骨修复部位，15～60min内固化完成缺损的修复。
步骤(1)中的磷酸钙为磷酸四钙、磷酸氢钙及锶磷灰石组成，其中，磷酸四钙与磷酸氢钙的摩尔比为1:1，锶磷灰石占磷酸钙质量百分含量为1～20％；
磷酸四钙、磷酸氢钙的粒径为50～150μm，锶磷灰石的粒径为0.1～2μm，锶磷灰石中优选锶占锶钙的摩尔比为6～10:10；
步骤(1)中的PVA溶液，PVA的质量分数为1～10％；
步骤(1)烧结过程中，优选烧结温度800～1200℃，烧结时间5～18h；
步骤(2)中纤维素优选羟丙基纤维素，优选羟丙基纤维素占溶液的质量百分含量为3～5％。
本发明的优点在于：磷酸钙烧结的多孔陶瓷颗粒成分与人体骨成分类似，硫酸钙骨水泥承载多孔陶瓷颗粒微创注射到缺损部位，以多孔陶瓷颗粒替代自体骨颗粒，加速骨缺损的修复，并改善陶瓷类骨填充材料注射性差、力学强度差的问题。
通过溶液喷雾振动造粒，以磷酸四钙、磷酸氢钙为原料，以锶磷灰石为籽晶，控制反应的温度、湿度和时间，生成锶掺杂磷灰石，再经烧结造孔及提升锶磷灰石的结晶度及转变晶相，制备粒径可控的锶掺杂双相陶瓷，辅以硫酸钙水泥，纤维素的加入增强了骨填充材料抗水溃散性、粘结性及韧性，采用微创注射到骨缺损部位，增强骨填充材料的力学性能，避免了开放手术操作，并随着添加的吡咯喹啉醌释放增强机体的免疫力，大大降低手术感染的风险，提升骨填充材料的诱导性，加速骨缺损的修复。注射型骨填充材料的抗压强度均在10MPa以上，满足人体松质骨修复的需要。
附图说明
图1：可注射型骨填充材料的抗压强度图
图2：制备的多孔陶瓷的SEM图
具体实施方式
下面结合实施例对本发明的内容作进一步的详细说明，但本发明的实施方式不限于此。
注射型骨填充材料组成与质量分数为20～50％的锶掺杂双相陶瓷与50～80％的硫酸钙水泥组成。硫酸钙水泥由粉液两部分组成，粉体为硫酸钙，液体为含0.5～5％吡咯喹啉醌的0.5～10％的纤维素溶液。
(1)锶掺杂双相陶瓷颗粒的制备：将30～80％质量分数的磷酸钙与20～70％质量分数的PVA颗粒混合均匀，通过喷雾PVA溶液振动造粒制备磷酸钙/PVA复合颗粒，其中，PVA颗粒粒径为200～350μm；
将制备的磷酸钙/PVA复合颗粒，经反应24～72h，转移到烧结炉中，烧结温度为350～1250℃，烧结时间为3～36h，室温冷却，得到锶掺杂双相陶瓷颗粒，其粒径为500～2000μm，孔径为100～300μm；
(2)硫酸钙水泥的制备：按照粉液质量比3:2将硫酸钙粉体和含0.5～5％吡咯喹啉醌的0.5～10％的纤维素溶液混合均匀，得到硫酸钙水泥；
(3)骨填充材料的制备：将占骨填充材料质量分数为20～50％的锶掺杂双相陶瓷颗粒推入到占骨填充材料质量分数为50～80％的硫酸钙水泥中，得到注射型骨填充材料，注射到骨修复部位，15～60min内固化完成缺损的修复。
磷酸钙为磷酸四钙、磷酸氢钙及锶磷灰石组成，其中，磷酸四钙与磷酸氢钙的摩尔比为1:1，锶磷灰石占磷酸钙质量百分含量为1～20％。
实施例1
注射型骨填充材料组成与质量分数为20％的锶掺杂双相陶瓷与80％的硫酸钙水泥组成。硫酸钙水泥由粉液两部分组成，粉体为硫酸钙，液体为含0.5％吡咯喹啉醌的5％的纤维素溶液。
(1)锶掺杂双相陶瓷颗粒的制备：将50％质量分数的磷酸钙与50％质量分数的PVA颗粒混合均匀，通过喷雾质量分数为1％的PVA溶液振动造粒制备磷酸钙/PVA复合颗粒，PVA颗粒粒径为200～350μm；
将制备的磷酸钙/PVA复合颗粒，经反应72h，转移到烧结炉中，烧结温度为1000℃，烧结时间为24h，室温冷却，得到多孔陶瓷颗粒，其粒径为500～2000μm，孔径为100～300μm；
(2)硫酸钙水泥的制备：按照粉液质量比3:2将硫酸钙和含0.5％吡咯喹啉醌的5％的纤维素溶液混合均匀，得到硫酸钙骨水泥；
(3)骨填充材料的制备：再将占骨填充材料质量分数为20％的锶掺杂双相陶瓷颗粒推入到占骨填充材料质量分数为80％的硫酸钙水泥中，得到注射型骨填充材料，注射到骨修复部位，15min内固化完成缺损的修复。
磷酸钙为磷酸四钙、磷酸氢钙及锶磷灰石组成，其中，磷酸四钙与磷酸氢钙的摩尔比为1:1，锶磷灰石占磷酸钙质量百分含量为20％；
将骨填充材料制备成Φ6mm×12mm的试样，在37℃、100％相对湿度环境中固化24h，进行抗压强度测试，平均值为17.59Mpa(如附图1-A所示)。
实施例2
注射型骨填充材料组成与质量分数为30％的锶掺杂双相陶瓷与70％的硫酸钙水泥组成。硫酸钙水泥由粉液两部分组成，粉体为硫酸钙，液体为含5％吡咯喹啉醌的0.5％的纤维素溶液。
(1)锶掺杂双相陶瓷颗粒的制备：将80％质量分数的磷酸钙与20％质量分数的PVA颗粒混合均匀，通过喷雾质量分数为10％的PVA溶液振动造粒制备磷酸钙/PVA复合颗粒，PVA颗粒粒径为200～350μm；
将制备的磷酸钙/PVA复合颗粒，经反应48h，转移到烧结炉中，烧结温度为1150℃，烧结时间为12h，室温冷却，得到多孔陶瓷颗粒，其粒径为500～2000μm，孔径为100～300μm；
(2)硫酸钙水泥的制备：按照粉液质量比3:2将硫酸钙和含5％吡咯喹啉醌的0.5％的纤维素溶液混合均匀，得到硫酸钙骨水泥；
(3)骨填充材料的制备：将占骨填充材料质量分数为30％的锶掺杂双相陶瓷颗粒推入到占骨填充材料质量分数为70％的硫酸钙水泥中，得到注射型骨填充材料，注射到骨修复部位，15min内固化完成缺损的修复。
磷酸钙为磷酸四钙、磷酸氢钙及锶磷灰石组成，其中，磷酸四钙与磷酸氢钙的摩尔比为1:1，锶磷灰石占磷酸钙质量百分含量为1％；
对制备的多孔陶瓷颗粒查看其围观形貌，如图2所示，孔径在100μm左右。
将骨填充材料制备成Φ6mm×12mm的试样，在37℃、100％相对湿度环境中固化24h，进行抗压强度测试，平均值为18.21Mpa(如附图1-B所示)。
实施例3
注射型骨填充材料组成与质量分数为50％的锶掺杂双相陶瓷与50％的硫酸钙水泥组成。硫酸钙水泥由粉液两部分组成，粉体为硫酸钙，液体为含1％吡咯喹啉醌的10％的纤维素溶液。
(1)锶掺杂双相陶瓷颗粒的制备：将30％质量分数的磷酸钙与70％质量分数的PVA颗粒混合均匀，通过喷雾质量分数为3％的PVA溶液振动造粒制备磷酸钙/PVA复合颗粒，PVA颗粒粒径为200～350μm；
将制备的磷酸钙/PVA复合颗粒，经反应24h，转移到烧结炉中，烧结温度为1250℃，烧结时间为3h，室温冷却，得到多孔陶瓷颗粒，其粒径为500～2000μm，孔径为100～300μm；
(2)硫酸钙水泥的制备：按照粉液质量比3:2将硫酸钙和含1％吡咯喹啉醌的10％的纤维素溶液混合均匀，得到硫酸钙骨水泥；
(3)骨填充材料的制备：将占骨填充材料质量分数为50％的锶掺杂双相陶瓷颗粒推入到占骨填充材料质量分数为50％的硫酸钙水泥中，得到注射型骨填充材料，注射到骨修复部位，15min内固化完成缺损的修复。
磷酸钙为磷酸四钙、磷酸氢钙及锶磷灰石组成，其中，磷酸四钙与磷酸氢钙的摩尔比为1:1，锶磷灰石占磷酸钙质量百分含量为10％；
将骨填充材料制备成Φ6mm×12mm的试样，在37℃、100％相对湿度环境中固化24h，进行抗压强度测试，平均值为14.55Mpa(如附图1-C所示)。
实施例4
注射型骨填充材料组成与质量分数为40％的锶掺杂双相陶瓷与60％的硫酸钙水泥组成。硫酸钙水泥由粉液两部分组成，粉体为硫酸钙，液体为含1％吡咯喹啉醌的3％的纤维素溶液。
(1)锶掺杂双相陶瓷颗粒的制备：将70％质量分数的磷酸钙与30％质量分数的PVA颗粒混合均匀，通过喷雾质量分数为2％的PVA溶液振动造粒制备磷酸钙/PVA复合颗粒，PVA颗粒粒径为200～350μm；
将制备的磷酸钙/PVA复合颗粒，经反应36h，转移到烧结炉中，烧结温度为800℃，烧结时间为36h，室温冷却，得到多孔陶瓷颗粒，其粒径为500～2000μm，孔径为100～300μm；
(2)硫酸钙水泥的制备：按照粉液质量比3:2将硫酸钙和含1％吡咯喹啉醌的3％的纤维素溶液混合均匀，得到硫酸钙水泥；
(3)骨填充材料的制备：将占骨填充材料质量分数为40％的锶掺杂双相陶瓷颗粒推入到占骨填充材料质量分数为60％的硫酸钙水泥中，得到注射型骨填充材料，注射到骨修复部位，15min内固化完成缺损的修复。
磷酸钙为磷酸四钙、磷酸氢钙及锶磷灰石组成，其中，磷酸四钙与磷酸氢钙的摩尔比为1:1，锶磷灰石占磷酸钙质量百分含量为15％；
将骨填充材料制备成Φ6mm×12mm的试样，在37℃、100％相对湿度环境中固化24h，进行抗压强度测试，平均值为16.13Mpa(如附图1-D所示)。
Claims (8)
1.一种注射型骨填充材料，其特征在于，骨填充材料组成与质量分数为20～50％的多孔陶瓷颗粒与50～80％的硫酸钙水泥组成。
2.如权利要求1所述的注射型骨填充材料，其特征在于，多孔陶瓷颗粒为锶掺杂双相陶瓷；硫酸钙水泥由粉液两部分组成，粉体为硫酸钙粉体，液体为含0.5～5％吡咯喹啉醌的0.5～10％的纤维素溶液。
3.如权利要求1所述的注射型骨填充材料制备方法，其特征在于，按照以下步骤：
(1)多孔陶瓷颗粒的制备：将30～80％质量分数的磷酸钙与20～70％质量分数的PVA颗粒混合均匀，通过喷雾PVA溶液振动造粒制备磷酸钙/PVA复合颗粒，其中，PVA颗粒粒径为200～350μm；
将制备的磷酸钙/PVA复合颗粒，经反应24～72h，转移到烧结炉中，烧结温度为350～1250℃，烧结时间为3～36h，室温冷却，得到多孔陶瓷颗粒，其粒径为500～2000μm，孔径为100～300μm；
(2)硫酸钙水泥的制备：按照粉液质量比3:2将硫酸钙粉体和含0.5～5％吡咯喹啉醌的0.5～10％的纤维素溶液混合均匀，得到硫酸钙水泥；
(3)骨填充材料的制备：将占骨填充材料质量分数为20～50％的多孔陶瓷颗粒推入到占骨填充材料质量分数为50～80％的硫酸钙水泥中，得到注射型骨填充材料，注射到骨修复部位，15～60min内固化完成缺损的修复。
4.如权利要求3所述的方法，其特征在于，步骤(1)中的磷酸钙为磷酸四钙、磷酸氢钙及锶磷灰石，其中，磷酸四钙与磷酸氢钙的摩尔比为1:1，锶磷灰石占磷酸钙质量百分含量为1～20％。
5.如权利要求4所述的方法，其特征在于，磷酸四钙和磷酸氢钙的粒径为50～150μm，锶磷灰石的粒径为0.1～2μm，锶磷灰石中锶占锶钙的摩尔比为6～10:10。
6.如权利要求3所述的方法，其特征在于，步骤(1)中的PVA溶液，PVA的质量百分含量为1～10％。
7.如权利要求3所述的方法，其特征在于，步骤(1)烧结过程中，烧结温度800～1200℃，烧结时间5～18h。
8.如权利要求3所述的方法，其特征在于，步骤(2)中纤维素为羟丙基纤维素，羟丙基纤维素占溶液的质量百分含量为3～5％。
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