CN109620796A - 一种基于低免疫原性多肽微米管及其制备方法 - Google Patents
一种基于低免疫原性多肽微米管及其制备方法 Download PDFInfo
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Abstract
一种基于低免疫原性多肽自组装的微米管的制备方法，包括以下步骤：1）首先将低免疫原性多肽在低温下溶解并快速搅拌，经超声处理得到多肽原液；2）随后在pH为6.0~8.0的磷酸二氢钠/磷酸氢二钠缓冲液将多肽配制浓度为0.01%~30%（w/v）的溶液，在37℃下，避光环境下，于生化培养箱内组装6h~24h；3）接着采用超临界CO2干燥或冷冻干燥或常温干燥对溶液进行干燥，最终可得到低免疫原性多肽微米管；本发明工艺简单易行，得到的微米管尺寸均一，形貌规整，性质稳定，且具有良好的生物相容性、可生物降解性和生物安全性，可用作药物载体材料、止血材料、组织工程支架、高级敷料、美容材料等。
Description
技术领域
本发明属于生物医用材料技术领域，涉及了一种基于低免疫原性多肽微米管及其制备方法。
背景技术
微米管作为一种特殊结构的微米材料有其特别的性能和用途。自从微米管被首次发现，此后各种材料的微米管的研究一直是国际新材料领域的前沿和热点，并取得令人瞩目的成就。科学界人士预言，多肽微米管以其独特的结构和优异的生物学性能，尤其是在可控生物降解方面有着独特的优势，将在医药学领域有着诱人的应用前景和巨大潜在应用价值。
多肽具有高生物相容性，低免疫原性，优异的生物活性和合适的生物降解性等诸多优点。自组装指的是以一个分子或多个分子为基本单元，通过非共价键力驱动，以自下而上的构筑方式，自发形成具有高度有序的、稳定的和规整的，且具有一定微观形貌的聚集体。多肽分子自组装以其丰富的自组装驱动力，特殊的功能及良好的生物相容性，在生物材料、药物运输、组织工程等方面具有广泛的应用前景。
综上所述，本发明为了解决目前生物微米材料形貌尺寸不宜调控，生物相容性差，制备得到了一种基于低免疫原性多肽微米管，该微米管具有形貌规整、尺寸均一的形貌特点，并且多肽微米管有良好的生物相容性、可生物降解性和生物安全性等优良性能，可用作药物载体材料、止血材料、组织工程支架、高级敷料等。
发明内容
本发明的目的是针对现有技术的不足而提供的基于低免疫原性多肽微米管。该微米管具有形貌规整、尺寸均一的形貌特点，并且多肽微米管有良好的生物相容性、可生物降解性和生物安全性等优良性能，可用作药物载体材料、止血材料、组织工程支架、高级敷料等。
为实现上述目的，本发明采用如下技术方案：
1）将低免疫原性多肽与磷酸氢二钠/磷酸二氢钠缓冲液（PBS）比例为0.01%~30%（w/v），在pH 6.0～8.0下，低温下搅拌充分溶解并超声处理，至清澈透明后；
2）将其在37℃下，避光环境下，放置生化培养箱中组装6h~24h；
3）再将溶液，利用超临界CO2干燥或冷冻干燥或常温干燥，将干燥后样品用扫描电镜检测可得到低免疫原性多肽自组装微米管。
本技术与现有技术相比，具有如下优点：
（1）与传统动物源胶原蛋白不同，本发明以低免疫原性多肽为原料，从根源上保证了材料的生物安全性，同时，低免疫原性多肽同样具有优异的生物活性；
（2）本发明制备的低免疫原性多肽微米管操作简便易行，制备的微米管具有较好的生物相容性，生物活性及生物降解性，有望在药物载体、组织工程、高级敷料等领域得到应用。
（3）本发明采用以多肽分子自组装能够特性设计低免疫原性多肽的微观形貌，使得多肽微米管具有形貌规整、尺寸均一。
附图说明
图1为本发明的低免疫原性多肽微米管。
具体实施方式
下面通过实施对本发明进行具体的描述，有必要在此指出的是本实施例只用于对本发明进行进一步说明，而不能理解为对本发明保护范围的限制，该领域的技术熟练人员可以根据上述发明的内容作出非本质的改进和调整。
实施例1
1）将低免疫原性多肽与PBS比例为0.01%（w/v），在pH 6.0下，低温下搅拌充分溶解并超声处理，至清澈透明后；
2）将其在37℃下，避光环境下，放置生化培养箱中组装6h；
3）再将溶液，利用超临界CO2干燥，将干燥后样品用扫描电镜检测可得到低免疫原性多肽自组装微米管。
上述步骤中，质量与体积的对应关系为1质量份：1体积=1g：1ml。
本微米管的平均直径在1μm。
实施例2
1）将低免疫原性多肽与PBS比例为0.1%（w/v），在pH 7.0下，低温下搅拌充分溶解并超声处理，至清澈透明后；
2）将其在37℃下，避光环境下，放置生化培养箱中组装12h；
3）再将溶液，利用冷冻干燥，将干燥后样品用扫描电镜检测可得到低免疫原性多肽自组装微米管。
上述步骤中，质量与体积的对应关系为1质量份：1体积=1g：1ml。
本微米管的平均直径在2μm。
实施例3
1）将低免疫原性多肽与PBS比例为10%（w/v），在pH 8.0下，低温下搅拌充分溶解并超声处理，至清澈透明后；
2）将其在37℃下，避光环境下，放置生化培养箱中组装24h；
3）再将溶液，利用常温干燥，将干燥后样品用扫描电镜检测可得到低免疫原性多肽自组装微米管。
上述步骤中，质量与体积的对应关系为1质量份：1体积=1g：1ml
本微米管的平均直径在3μm。
实施例4
1）将低免疫原性多肽与PBS比例为0.1%（w/v），在pH 7.0下，低温下搅拌充分溶解并超声处理，至清澈透明后；
2）将其20℃下，避光环境下，放置生化培养箱中组装12h；
3）再将溶液，利用冷冻干燥，将干燥后样品用扫描电镜检测可得到低免疫原性多肽自组装微米管。
上述步骤中，质量与体积的对应关系为1质量份：1体积=1g：1ml。
Claims (7)
1.一种基于低免疫原性多肽自组装的微米管，其特征在于，由低免疫原性多肽自组织形成的管状形貌，具有微米级的管径。
2.一种基于低免疫原性多肽自组装的微米管的制备方法，其特征在于，包括以下步骤：
将低免疫原性多肽溶于以PBS缓冲液为分散介质的体系中，调节pH至6.0～8.0，避光环境下，20℃~40℃组装6h~24h，得到一种基于低免疫原性多肽自组装的微米管。
3.根据权利要求2所述的一种基于低免疫原性多肽自组装的微米管的制备方法，其特征在于，所述低免疫原性多肽的用量为0.01~30g每100mlPBS缓冲液。
4.根据权利要求2所述的一种基于低免疫原性多肽自组装的微米管的制备方法，其特征在于，具体步骤包括：
1）将低免疫原性多肽与磷酸氢二钠/磷酸二氢钠缓冲液按0.01~30g/100ml，在pH 6.0～8.0下，低温下搅拌充分溶解并超声处理，至清澈透明；
2）将步骤1）产物在37℃下，避光环境下，放置生化培养箱中组装6h~24h；
3）将步骤2）产物，利用超临界CO2干燥或冷冻干燥或常温干燥，可制备得到低免疫原性多肽自组装微米管。
5.根据权利要求4所述的一种基于低免疫原性多肽自组装的微米管的制备方法，其特征在于，具体步骤包括：
1）将低免疫原性多肽与PBS比例为0.01g/100ml，在pH 6.0下，低温下搅拌充分溶解并超声处理，至清澈透明；
2）将其在37℃下，避光环境下，放置生化培养箱中组装6h；
3）再将溶液，利用超临界CO2干燥，将干燥后样品可制备得到低免疫原性多肽自组装微米管。
6.根据权利要求4所述的一种基于低免疫原性多肽自组装的微米管的制备方法，其特征在于，具体步骤包括：
1）将低免疫原性多肽与PBS比例为0.1g/100ml，在pH 7.0下，低温下搅拌充分溶解并超声处理，至清澈透明；
2）将其在37℃下，避光环境中，放置生化培养箱中组装12h；
3）再将溶液，利用冷冻干燥，可制备得到低免疫原性多肽自组装微米管。
7.根据权利要求4所述的一种基于低免疫原性多肽自组装的微米管的制备方法，其特征在于，具体步骤包括：
1）将低免疫原性多肽与PBS比例为10g/100ml，在pH 8.0下，低温下搅拌充分溶解并超声处理，至清澈透明；
2）将其在37℃下，避光环境中，放置生化培养箱中组装24h；
3）再将溶液，利用常温干燥，可制备得到低免疫原性多肽自组装微米管。
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| US20180036702A1 (en) * | 2015-03-03 | 2018-02-08 | Spheritech Ltd | Microparticles |
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| US20180036702A1 (en) * | 2015-03-03 | 2018-02-08 | Spheritech Ltd | Microparticles |
| CN107630059A (zh) * | 2016-07-19 | 2018-01-26 | 华南生物医药研究院 | 新型自组装胶原蛋白及制备方法 |
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