CN113116858A - 一种载伊班膦酸钠plga微球及采用该微球的复合组织工程骨的制备方法 - Google Patents
一种载伊班膦酸钠plga微球及采用该微球的复合组织工程骨的制备方法 Download PDFInfo
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Abstract
本发明涉及药物化学技术领域，且公开了一种载伊班膦酸钠PLGA微球及采用该微球的复合组织工程骨的制备方法，运用复乳溶剂蒸发法制备方法包括以下步骤：将载伊班膦酸钠PLGA溶解在二氯甲烷溶液中，并通过涡旋搅拌以混合形成均匀溶液，将混合后的溶液转移到含有PVA水溶液的烧杯中搅拌，将溶液搅拌以使以使溶剂蒸发并稳定微球形态，使用蒸馏水对微球形态物洗涤三次以分离获得载伊班膦酸钠PLGA微球，本发明中，载伊班膦酸钠/PLGA/CPC复合组织工程骨具有良好的生物相容性和成骨活性，可促进骨髓间充质干细胞的黏附、增殖和成骨分化，利于坏死股骨头局部的新骨形成，加速坏死股骨头的修复和愈合，可用于股骨头缺血性坏死的治疗。
Description
技术领域
本发明涉及药物化学技术领域，具体为一种载伊班膦酸钠PLGA微球及采用该微球的复合组织工程骨的制备方法。
背景技术
股骨头坏死，又称股骨头缺血性坏死(Avascular Necrosis of the FemoralHead，ANFH)是骨科常见的疾病之一。其主要由激素、风湿疾病、血液疾病等引起，首先影响股骨头的血液供应，进而造成股骨头的骨质破坏，引起股骨头的坏死甚至塌陷，往往引发髋部肌肉痉挛、髋关节功能受限，严重影响患者的生活质量。随着骨组织工程技术的发展，对于股骨头坏死的治疗由最初的单一药物或手术简单治疗，进展到联合药物、微创手术以及骨组织工程技术手段进行综合性的治疗，以期达到理想的效果。理想的骨组织工程材料应具有良好的生物相容性、易成型性和合适的孔径，以保证营养物质的供应和新骨组织的生长。单一的生物材料通常不可能实现所有的功能。因此，不同材料的组成成为研究的重点。磷酸钙骨水泥（Calcium phosphate bone cement，CPC）是一种具有良好生物相容性和骨传导性的骨修复材料，被认为是修复骨缺损的理想基质材料。聚乳酸-羟基乙酸（Poly-lactic-co-glycolic acid，PLGA）具有良好的生物相容性和生物降解性，已被FDA批准用于临床，在骨组织工程中得到广泛应用。PLGA还可用于载体药物、药物和细胞因子的缓释。伊班膦酸钠是第三代含氮双膦酸盐类的药物，能强烈抑制骨吸收，防止骨丢失，增加骨量，降低骨折发生率
现有的伊班膦酸钠药物大多采用注射的方式进行使用，对股骨头进行微创髓心减压术后缺少一种既提供即刻支撑力，同时能够利用伊班膦酸钠缓释促进新生骨的形成、改善应力、防止股骨头的塌陷，用于修复坏死股骨头的工程骨。
发明内容
针对现有技术的不足，本发明提供了一种载伊班膦酸钠PLGA微球及采用该微球的复合组织工程骨的制备方法，以解决了背景技术中提出的问题。
为实现上述目的，本发明提供如下技术方案：
一种载伊班膦酸钠PLGA微球的制备方法，运用复乳溶剂蒸发法制备方法包括以下步骤：
S1、将1g的载伊班膦酸钠PLGA溶解在6 ml二氯甲烷溶液中，并通过涡旋搅拌60秒以混合形成均匀溶液；
S2、将所述步骤S1中混合后的溶液转移到含有100 ml的0.3％PVA水溶液的烧杯中搅拌；
S3、将所述步骤S2中混合后的溶液以1200 rpm的转速搅拌6小时以使以使溶剂蒸发并稳定微球形态；
S4、使用蒸馏水对所述步骤S3中搅拌后的微球形态物洗涤三次以分离获得载伊班膦酸钠PLGA微球。
优选的，所述步骤S2中的二氯甲烷溶液中含有浓度为0.01mg/μl的伊班膦酸钠。
优选的，所述步骤S1中的二氯甲烷溶液和所述步骤S2中的PVA水溶液使用前均使用0.22μm滤膜过滤器过滤。
优选的，在所述步骤S4之后，所述制备方法还包括步骤S5：
将所述步骤4中得到的载伊班膦酸钠PLGA微球冷冻干燥24小时，并储存于-20℃环境中备用。
本发明还提供了一种复合组织工程骨的制备方法，包括磷酸钙骨水泥和上述任一项载伊班膦酸钠PLGA微球，所述磷酸钙骨水泥由固相粉末和液相固化液两部分组成，所述固相粉末的主要成份包括β-磷酸三钙-80％、无水磷酸二钙-10％、羟磷灰石-5％和纳米羟基磷灰石-5％，所述液相固化液为2%的Na2HPO4溶液。
优选的，该复合组织工程骨的制备方法包括以下步骤：
N1、将所述步骤S5中的载伊班膦酸钠PLGA微球、所述固相粉末、所述液相固化液在室温20℃下混合搅拌；
N2、将所述步骤N1中混合后的物料搅拌成糊状后推入圆柱形模具；
N3、将N2中得到的载伊班膦酸钠/PLGA/CPC复合组织工程骨支架冷冻干燥后，于-20℃储存备用；
所述步骤N1中液相固化液的固液比为4:1.5。
优选的，所述步骤N2中圆柱形模具的直径为八毫米且长度为十五毫米。
有益效果
与现有技术相比，本发明提供了一种载伊班膦酸钠PLGA微球及采用该微球的复合组织工程骨的制备方法，具备以下有益效果：
本发明中，利用改进的复乳溶剂蒸发法能够成功制备出载伊班膦酸钠的PLGA微球，PLGA微球是良好的伊班膦酸钠的药物载体和缓释体，对伊班膦酸钠具有较高的载药率，载伊班膦酸钠的PLGA微球在降解后，可使药物缓慢释放，载伊班膦酸钠/PLGA/CPC复合组织工程骨支架具有良好的材料学性能，有合适的孔径结构和力学性能，体外实验和动物实验显示载伊班膦酸钠/PLGA/CPC复合组织工程骨具有良好的生物相容性和成骨活性，可促进骨髓间充质干细胞的黏附、增殖和成骨分化，利于坏死股骨头局部的新骨形成，加速坏死股骨头的修复和愈合，可用于股骨头缺血性坏死的治疗。
具体实施方式
下面对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
一种载伊班膦酸钠PLGA微球的制备方法，运用复乳溶剂蒸发法制备方法包括以下步骤：
S1、将1g的载伊班膦酸钠PLGA溶解在6 ml二氯甲烷溶液中，并通过涡旋搅拌60秒以混合形成均匀溶液；
S2、将步骤S1中混合后的溶液转移到含有100 ml的0.3％PVA水溶液的烧杯中搅拌；
S3、将步骤S2中混合后的溶液以1200 rpm的转速搅拌6小时以使以使溶剂蒸发并稳定微球形态；
S4、使用蒸馏水对步骤S3中搅拌后的微球形态物洗涤三次以分离获得载伊班膦酸钠PLGA微球。
本实施例中，步骤S2中的二氯甲烷溶液中含有浓度为0.01mg/μl的伊班膦酸钠。
步骤S1中的二氯甲烷溶液和步骤S2中的PVA水溶液使用前均使用0.22μm滤膜过滤器过滤。
在步骤S4之后，制备方法还包括步骤S5：将步骤4中得到的载伊班膦酸钠PLGA微球冷冻干燥24小时，并储存于-20℃环境中备用
本发明还提供了一种复合组织工程骨的制备方法，包括磷酸钙骨水泥和上述任一项载伊班膦酸钠PLGA微球，磷酸钙骨水泥由固相粉末和液相固化液两部分组成，固相粉末的主要成份包括β-磷酸三钙-80％、无水磷酸二钙-10％、羟磷灰石-5％和纳米羟基磷灰石-5％，液相固化液为2%的Na2HPO4溶液。
采用该载伊班膦酸钠PLGA微球的复合组织工程骨的制备方法包括以下步骤：
N1、将步骤S5中的载伊班膦酸钠PLGA微球、固相粉末、液相固化液在室温20℃下混合搅拌；
N2、将步骤N1中混合后的物料搅拌成糊状后推入圆柱形模具；
N3、将N2中得到的载伊班膦酸钠/PLGA/CPC复合组织工程骨支架冷冻干燥后，于-20℃储存备用；
步骤N1中液相固化液的固液比为4:1.5。
步骤N2中圆柱形模具的直径为八毫米且长度为十五毫米。
从以上的描述中，可以看出，本发明上述的实施例实现了如下技术效果：利用改进的复乳溶剂蒸发法能够成功制备出载伊班膦酸钠的PLGA微球，PLGA微球是良好的伊班膦酸钠的药物载体和缓释体，对伊班膦酸钠具有较高的载药率，载伊班膦酸钠的PLGA微球在降解后，可使药物缓慢释放，载伊班膦酸钠/PLGA/CPC复合组织工程骨支架具有良好的材料学性能，有合适的孔径结构和力学性能，体外实验和动物实验显示载伊班膦酸钠/PLGA/CPC复合组织工程骨具有良好的生物相容性和成骨活性，可促进骨髓间充质干细胞的黏附、增殖和成骨分化，利于坏死股骨头局部的新骨形成，加速坏死股骨头的修复和愈合，可用于股骨头缺血性坏死的治疗。
尽管已经示出和描述了本发明的实施例，对于本领域的普通技术人员而言，可以理解在不脱离本发明的原理和精神的情况下可以对这些实施例进行多种变化、修改、替换和变型，本发明的范围由所附权利要求及其等同物限定。
Claims (7)
1.一种载伊班膦酸钠PLGA微球的制备方法，其特征在于：运用复乳溶剂蒸发法制备方法包括以下步骤：
S1、将1g的载伊班膦酸钠PLGA溶解在6 ml二氯甲烷溶液中，并通过涡旋搅拌60秒以混合形成均匀溶液；
S2、将所述步骤S1中混合后的溶液转移到含有100 ml的0.3％PVA水溶液的烧杯中搅拌；
S3、将所述步骤S2中混合后的溶液以1200 rpm的转速搅拌6小时以使以使溶剂蒸发并稳定微球形态；
S4、使用蒸馏水对所述步骤S3中搅拌后的微球形态物洗涤三次以分离获得载伊班膦酸钠PLGA微球。
2.根据权利要求1所述的一种载伊班膦酸钠PLGA微球的制备方法，其特征在于：所述步骤S2中的二氯甲烷溶液中含有浓度为0.01mg/μl的伊班膦酸钠。
3.根据权利要求1所述的一种载伊班膦酸钠PLGA微球的制备方法，其特征在于：所述步骤S1中的二氯甲烷溶液和所述步骤S2中的PVA水溶液使用前均使用0.22μm滤膜过滤器过滤。
4.根据权利要求1所述的一种载伊班膦酸钠PLGA微球的制备方法，其特征在于：在所述步骤S4之后，所述制备方法还包括步骤S5：将所述步骤4中得到的载伊班膦酸钠PLGA微球冷冻干燥24小时，并储存于-20℃环境中备用。
5.一种复合组织工程骨的制备方法，其特征在于：包括磷酸钙骨水泥和如权利要求1-4任一所述的载伊班膦酸钠PLGA微球，所述磷酸钙骨水泥由固相粉末和液相固化液两部分组成，所述固相粉末的主要成份包括β-磷酸三钙-80％、无水磷酸二钙-10％、羟磷灰石-5％和纳米羟基磷灰石-5％，所述液相固化液为2%的Na2HPO4溶液。
6.根据权利要求5所述的一种复合组织工程骨的制备方法，其特征在于：该复合组织工程骨的制备方法包括以下步骤：
N1、将所述步骤S5中的载伊班膦酸钠PLGA微球、所述固相粉末、所述液相固化液在室温20℃下混合搅拌；
N2、将所述步骤N1中混合后的物料搅拌成糊状后推入圆柱形模具；
N3、将N2中得到的载伊班膦酸钠/PLGA/CPC复合组织工程骨支架冷冻干燥后，于-20℃储存备用；所述步骤N1中液相固化液的固液比为4:1.5。
7.根据权利要求6所述的一种复合组织工程骨的制备方法，其特征在于：所述步骤N2中圆柱形模具的直径为八毫米且长度为十五毫米。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115025285A (zh) * | 2022-06-22 | 2022-09-09 | 深圳市前海蛇口自贸区医院(深圳市南山区蛇口人民医院) | PLGA/MgO-阿仑膦酸钠水凝胶微球及其制备方法 |
| CN115317667A (zh) * | 2022-09-23 | 2022-11-11 | 上海纳米技术及应用国家工程研究中心有限公司 | 载药plga微球改性的pmma骨水泥的制备方法及其产品和应用 |
| CN115708894A (zh) * | 2022-09-16 | 2023-02-24 | 张皓轩 | 一种用于治疗股骨头坏死的复合骨组织支架及其制备方法 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050260115A1 (en) * | 2002-05-06 | 2005-11-24 | Tas Ahmet C | Method of preparing porous calcium phosphate granules |
| CN100998597A (zh) * | 2007-01-12 | 2007-07-18 | 西北工业大学 | 二膦酸盐微球组合物及其制备方法 |
| CN101687059A (zh) * | 2007-02-14 | 2010-03-31 | 格拉夫蒂斯公司 | 释放骨吸收抑制剂的可注射型磷酸钙水泥 |
| US20100313791A1 (en) * | 2009-06-12 | 2010-12-16 | Kaohsiung Medical University | Calcium phosphate bone cement, precursor thereof and fabrication method thereof |
| CN102114271A (zh) * | 2011-02-24 | 2011-07-06 | 西南交通大学 | 载多种药物的磷酸钙骨水泥粉末 |
| CN104105509A (zh) * | 2012-01-19 | 2014-10-15 | 德普伊国际有限公司 | 骨填料组合物 |
-
2021
- 2021-03-26 CN CN202110325180.0A patent/CN113116858A/zh active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050260115A1 (en) * | 2002-05-06 | 2005-11-24 | Tas Ahmet C | Method of preparing porous calcium phosphate granules |
| CN100998597A (zh) * | 2007-01-12 | 2007-07-18 | 西北工业大学 | 二膦酸盐微球组合物及其制备方法 |
| CN101687059A (zh) * | 2007-02-14 | 2010-03-31 | 格拉夫蒂斯公司 | 释放骨吸收抑制剂的可注射型磷酸钙水泥 |
| US20100313791A1 (en) * | 2009-06-12 | 2010-12-16 | Kaohsiung Medical University | Calcium phosphate bone cement, precursor thereof and fabrication method thereof |
| CN102114271A (zh) * | 2011-02-24 | 2011-07-06 | 西南交通大学 | 载多种药物的磷酸钙骨水泥粉末 |
| CN104105509A (zh) * | 2012-01-19 | 2014-10-15 | 德普伊国际有限公司 | 骨填料组合物 |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115025285A (zh) * | 2022-06-22 | 2022-09-09 | 深圳市前海蛇口自贸区医院(深圳市南山区蛇口人民医院) | PLGA/MgO-阿仑膦酸钠水凝胶微球及其制备方法 |
| CN115708894A (zh) * | 2022-09-16 | 2023-02-24 | 张皓轩 | 一种用于治疗股骨头坏死的复合骨组织支架及其制备方法 |
| CN115317667A (zh) * | 2022-09-23 | 2022-11-11 | 上海纳米技术及应用国家工程研究中心有限公司 | 载药plga微球改性的pmma骨水泥的制备方法及其产品和应用 |
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