CN107217322B - 一种载药长丝及其制备方法 - Google Patents
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Abstract
本发明公开了一种载药长丝及其制备方法,载药长丝的组成包括丝素蛋白和药物,丝素蛋白和药物的质量比为99.9:0.1‑70:30;载药长丝的应力为0.1MPa‑1GPa,伸长率为0.1%‑80%,直径为0.5μm‑300μm。本发明的载药长丝具有抗肿瘤和抗菌消炎功能,载药长丝具有良好的强力、伸长、韧性,丝素蛋白因具有可控的降解性,同时,也对药物的释放速率起到一定作用,可用于手术缝合线、编织生物支架材料和功能性纱布等,应用前景广阔。本发明的载药长丝制备过程条件温和可控,制备工艺简单。
Description
技术领域
本发明属于蚕丝医用材料技术领域,具体涉及一种载药长丝及其制备方法。
背景技术
蚕丝因与人体胶原蛋白的氨基酸组成相似,具有良好的生物相容性,是制备医、卫用制品较为理想的原料,例如:手术缝合线、功能性纱布、组织支架、药物载体等。因此,如何利用蚕丝蛋白为原料制备具有优异理化性能的再生长丝成为重点研究的方向。
美国专利US4233212A、US005252285A公开了一种制备再生丝素纤维的方法,首先将丝素纤维溶解到盐溶液中,透析除盐,成膜,然后,再用六氟异丙醇溶解再生丝素进行纺丝获得再生丝素纤维。David M. Phillips等人采用湿法纺丝技术获得再生丝素蛋白纤维,该方法首先在1-甲基-3-乙基咪唑氯离子盐溶液体系中进行纺丝,然后,将牵伸丝在乙醇溶液中定型获得再生纤维(David M. Phillips, et al. J. Mater. Chem. 2005, 15:4206-4208.)。
中国专利CN103320886A公开了一种仿生再生丝素蛋白长丝纤维及其制备方法,采用湿法纺丝方法制备再生丝素蛋白长丝。中国专利CN1372023、CN102477592A公开了一种以蚕丝为原料,经脱胶、溶解等工序后,采用湿法纺丝获得生物可降解组织工程支架用再生丝素纤维。
现有的丝素蛋白再生材料制备方法制备的再生材料功能单一,力学性能较差,导致其应用存在一定难度。
发明内容
本发明的目的在于提供一种载药长丝及其制备方法,以克服现有的再生材料功能单一,力学性能较差的缺点。
为此,本发明提供了一种载药长丝,所述载药长丝的组成包括丝素蛋白和药物,所述丝素蛋白和所述药物的质量比为99.9:0.1-70:30;所述载药长丝的应力为0.1MPa-1GPa,伸长率为0.1%-80%,直径为0.5μm-300μm。
本发明还提供了一种载药长丝的制备方法,
方法Ⅰ包括以下步骤:
(1)制备离子溶解体系,所述离子溶解体系包括酸和盐离子,酸和盐离子的质量比为99:1-70:30;
(2)将脱胶蚕丝溶解于所述离子溶解体系中,搅拌均匀得到纺丝液,所述纺丝液中脱胶蚕丝质量分数为5%-25%,将所述纺丝液进行纺丝,得到初生长丝;
(3)用质量分数为0-100%的有机溶剂水溶液制备牵伸浴,将所述初生长丝在所述牵伸浴中进行牵伸,牵伸速度为1mm/min -20mm/min,牵伸温度为室温至60℃,牵伸倍率大于等于1倍,得到丝素蛋白长丝;
(4)将抗肿瘤药物和/或抗菌消炎药物溶解于去离子水中,得到含药物溶液,含药物水溶液中药物质量分数为1%-20%;将所述丝素蛋白长丝浸入所述含药物溶液中,静置沉积处理0.5-6h,得到载药长丝;
或者,方法Ⅱ包括以下步骤:
1)制备离子溶解体系,离子溶解体系包括酸和盐离子,酸和盐离子的质量比为99:1-70:30;
2)将脱胶蚕丝溶解于离子溶解体系中,搅拌均匀得到纺丝液;纺丝液中脱胶蚕丝质量分数为5%-25%;
3)将抗肿瘤药物和/或抗菌消炎药物溶解于去离子水中,得到含药物溶液,含药物水溶液中药物质量分数为1%-20%;将含药物溶液与浓度为1%-10%的丝素蛋白水溶液共混,制成电凝胶纳米药物球;
4)将所述电凝胶纳米药物球加入所述纺丝液中,搅拌均匀得到混合液,将所述混合液进行纺丝,得到初生长丝;
5)用质量分数为0-100%的有机溶剂水溶液制备牵伸浴,将所述初生长丝在所述牵伸浴中进行牵伸,牵伸速度1mm/min -20mm/min,牵伸温度为室温至60℃,牵伸倍率大于等于1倍,得到载药长丝。
与现有技术相比,本发明的优点和积极效果是:本发明提供了一种载药长丝及其制备方法,本发明的载药长丝具有抗肿瘤和抗菌消炎功能,载药长丝具有良好的强力、伸长和韧性,丝素蛋白因具有可控的降解性,同时,也对药物的释放速率起到一定作用,可用于手术缝合线、编织生物支架材料和功能性纱布等,应用前景广阔。本发明的载药长丝制备过程条件温和可控,制备工艺简单。
结合附图阅读本发明的具体实施方式后,本发明的其他特点和优点将变得更加清楚。
附图说明
图1是本发明实施例1制备得到的载药长丝的SEM图;
图2是本发明实施例1制备得到的载药长丝的力学性能曲线图。
具体实施方式
以下对本发明的具体实施方式进行详细说明,应当理解的是,此处所描述的具体实施方式仅用于说明和解释本发明,并不用于限制本发明。
本发明的载药长丝的组成包括丝素蛋白和药物,丝素蛋白和药物的质量比为99.9:0.1-70:30;载药长丝的应力为0.1MPa-1GPa,伸长率为0.1%-80%,直径为0.5μm-300μm。
药物包括抗肿瘤药物和/或抗菌消炎药物,当药物包括所述抗肿瘤药物和所述抗菌消炎药物时,所述抗肿瘤药物和所述抗菌消炎药物的质量比为1:99-30:70。
抗肿瘤药物包括盐酸表柔比星、阿霉素和表阿霉素中的一种或多种;抗菌消炎药物包括苯扎氯胺、阿司匹林、吲哚美辛和地塞米松中的一种或多种。
本发明的载药长丝具有抗肿瘤和抗菌消炎功能,载药长丝具有良好的强力、伸长和韧性,丝素蛋白因具有可控的降解性,同时,也对药物的释放速率起到一定作用,可用于手术缝合线、编织生物支架材料和功能性纱布等,应用前景广阔。
本发明还提供了载药长丝的制备方法:
方法Ⅰ包括以下步骤:
(1)制备离子溶解体系,所述离子溶解体系包括酸和盐离子,酸和盐离子的质量比为99:1-70:30;
(2)将脱胶蚕丝溶解于所述离子溶解体系中,搅拌均匀得到纺丝液,所述纺丝液中脱胶蚕丝质量分数为5%-25%,将所述纺丝液进行纺丝,得到初生长丝;
(3)用质量分数为0-100%的有机溶剂水溶液制备牵伸浴,将所述初生长丝在所述牵伸浴中进行牵伸,牵伸速度为1mm/min -20mm/min,牵伸温度为室温至60℃,牵伸倍率大于等于1倍,得到丝素蛋白长丝;
(4)将抗肿瘤药物和/或抗菌消炎药物溶解于去离子水中,得到含药物溶液,含药物水溶液中药物质量分数为1%-20%;将所述丝素蛋白长丝浸入所述含药物溶液中,静置沉积处理0.5-6h,得到载药长丝;
或者,方法Ⅱ包括以下步骤:
1)制备离子溶解体系,离子溶解体系包括酸和盐离子,酸和盐离子的质量比为99:1-70:30;
2)将脱胶蚕丝溶解于离子溶解体系中,搅拌均匀得到纺丝液;纺丝液中脱胶蚕丝质量分数为5%-25%;
3)将抗肿瘤药物和/或抗菌消炎药物溶解于去离子水中,得到含药物溶液,含药物水溶液中药物质量分数为1%-20%;将含药物溶液与浓度为1%-10%的丝素蛋白水溶液共混,制成电凝胶纳米药物球;
4)将所述电凝胶纳米药物球加入所述纺丝液中,搅拌均匀得到混合液,将所述混合液进行纺丝,得到初生长丝;
5)用质量分数为0-100%的有机溶剂水溶液制备牵伸浴,将所述初生长丝在所述牵伸浴中进行牵伸,牵伸速度1mm/min -20mm/min,牵伸温度为室温至60℃,牵伸倍率大于等于1倍,得到载药长丝。
实施例1
(1)取9.5g甲酸和0.5g贝壳粉在室温搅拌共混,制备得到甲酸/贝壳离子溶解体系;
(2)将1g脱胶蚕丝溶解于甲酸/贝壳离子溶解体系中,室温搅拌4h,制备成纺丝液;采用湿法纺丝方式对纺丝液进行纺丝,得到初生长丝;纺丝参数:凝固浴为质量分数为50%的乙醇溶液,纺丝速度为0.5mL/min;
(3)在室温条件下,将初生长丝在75%乙醇溶液中进行牵伸定型,牵伸速度为15mm/min,牵伸倍数为1倍,得到理化性能稳定的丝素蛋白长丝;
(4)将0.05g盐酸表柔比星药物溶解于去离子水中,制成质量分数为1%的药物溶液,将丝素蛋白长丝浸入药物溶液中,室温静置沉积2h,得到载药长丝。
图1为上述载药长丝的SEM图,由图1可以看出,载药长丝表面有许多纵向沟槽,有利于药物的大量负载。
图2为上述载药长丝的力学性能曲线图,由图2可以看出,载药长丝的伸长率在80%以上,应力在0.8MPa;可通过进一步牵伸,提高载药长丝内部丝素蛋白分子的取向度来进一步提高材料的应力值。
实施例2
(1)取95g甲酸和5g氯化钙在室温搅拌共混,制备得到甲酸/氯化钙离子溶解体系;
(2)将20g脱胶蚕丝溶解于甲酸/氯化钙离子溶解体系,室温搅拌4h,制备成纺丝液;采用湿法纺丝方式对纺丝液进行纺丝,得到初生长丝;纺丝参数:凝固浴为质量分数为50%的乙醇溶液,纺丝速度为0.5mL/min;
(3)室温条件下,将初生长丝在50%乙醇溶液中进行牵伸定型,牵伸速度为5mm/min,牵伸倍数为2倍,得到理化性能稳定的丝素蛋白长丝;
(4)将0.035g盐酸表柔比星药物和3.465g阿司匹林药物分别溶解于去离子水中,混合,制备成质量分数为5%的药物溶液,将丝素蛋白长丝浸入药物溶液中,室温静置沉积5h,得到载药长丝。
实施例3
1)取80g甲酸和20g蜗牛壳粉共混,在室温搅拌共混,制备得到甲酸/蜗牛壳离子溶液;
2)将25g脱胶蚕丝溶解于甲酸/蜗牛壳离子溶解体系,室温搅拌6h,制备成纺丝液;
3)取3g阿霉素和7g吲哚美辛溶解于40g去离子水中,制备成含药物溶液;将含药物溶液与浓度为10%的丝素蛋白水溶液共混,制备成电凝胶纳米药物球;
4)取5g电凝胶纳米药物球加入纺丝液中,搅拌1h,得到混合液,采用干湿法纺丝方式对混合液进行纺丝,得到初生长丝;纺丝参数:凝固浴为去离子水,纺丝速度为1mL/min;
5)将初生长丝在50%乙醇溶液中进行牵伸定型,牵伸速度为5mm/min,牵伸倍数为2倍,得到理化性能稳定的载药长丝。
实施例4
1)取70g磷酸和30g贝壳粉共混,在室温搅拌共混,制备得到磷酸/贝壳离子溶液;
2)将15g脱胶蚕丝溶解于磷酸/贝壳离子溶解体系中,室温搅拌6h,制备成纺丝液;
3)取3g阿霉素和7g吲哚美辛溶解于40g去离子水中,制备成含药物溶液;将含药物溶液与浓度为2%的丝素蛋白水溶液共混,制备成电凝胶纳米药物球;
4)取6g电凝胶纳米药物球加入纺丝液中,搅拌1h,得到混合液,采用干湿法纺丝方式对混合液进行纺丝,得到初生长丝;纺丝参数:凝固浴为去离子水,纺丝速度为1mL/min;
5)将初生长丝在50%乙醇溶液中进行牵伸定型,牵伸速度为10mm/min,牵伸倍数为2倍,得到理化性能稳定的载药长丝。
以上实施例仅用以说明本发明的技术方案,而非对其进行限制;尽管参照前述实施例对本发明进行了详细的说明,对于本领域的普通技术人员来说,依然可以对前述实施例所记载的技术方案进行修改,或者对其中部分技术特征进行等同替换;而这些修改或替换,并不使相应技术方案的本质脱离本发明所要求保护的技术方案的精神和范围。
Claims (2)
1.一种载药长丝,其特征在于,
所述载药长丝的制备方法包括:
1)取80g甲酸和20g蜗牛壳粉共混,在室温搅拌共混,制备得到甲酸/蜗牛壳离子溶液;
2)将25g脱胶蚕丝溶解于甲酸/蜗牛壳离子溶解体系,室温搅拌6h,制备成纺丝液;
3)取3g阿霉素和7g吲哚美辛溶解于40g去离子水中,制备成含药物溶液;将含药物溶液与浓度为10%的丝素蛋白水溶液共混,制备成电凝胶纳米药物球;
4)取5g电凝胶纳米药物球加入纺丝液中,搅拌1h,得到混合液,采用干湿法纺丝方式对混合液进行纺丝,得到初生长丝;纺丝参数:凝固浴为去离子水,纺丝速度为1mL/min;
5)将初生长丝在50%乙醇溶液中进行牵伸定型,牵伸速度为5mm/min,牵伸倍数为2倍,得到理化性能稳定的载药长丝。
2.一种载药长丝,其特征在于,
所述载药长丝的制备方法包括:
1)取70g磷酸和30g贝壳粉共混,在室温搅拌共混,制备得到磷酸/贝壳离子溶液;
2)将15g脱胶蚕丝溶解于磷酸/贝壳离子溶解体系中,室温搅拌6h,制备成纺丝液;
3)取3g阿霉素和7g吲哚美辛溶解于40g去离子水中,制备成含药物溶液;将含药物溶液与浓度为2%的丝素蛋白水溶液共混,制备成电凝胶纳米药物球;
4)取6g电凝胶纳米药物球加入纺丝液中,搅拌1h,得到混合液,采用干湿法纺丝方式对混合液进行纺丝,得到初生长丝;纺丝参数:凝固浴为去离子水,纺丝速度为1mL/min;
5)将初生长丝在50%乙醇溶液中进行牵伸定型,牵伸速度为10mm/min,牵伸倍数为2倍,得到理化性能稳定的载药长丝。
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