CN112220974B - 基于3d打印的丹参酮ⅱa血管支架的制备方法 - Google Patents

基于3d打印的丹参酮ⅱa血管支架的制备方法 Download PDF

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CN112220974B
CN112220974B CN202011187073.8A CN202011187073A CN112220974B CN 112220974 B CN112220974 B CN 112220974B CN 202011187073 A CN202011187073 A CN 202011187073A CN 112220974 B CN112220974 B CN 112220974B
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陶玲
沈祥春
蒋丹
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Abstract

本发明公开了基于3D打印的丹参酮ⅡA血管支架的制备方法,包括以下步骤:a、建模:设计血管支架的3D模型,得建模数据;b、制备打印溶液:称取丹参酮IIA原料药,加乙醇,在超声仪中溶解,得溶液A;另称取聚乳酸,与溶液A混合,并加入二氯甲烷溶解,得溶液B;c、3D打印血管支架:将建模数据输入3D打印机的程序中,将溶液B装入3D打印针筒,制备与血管内径大小一致的圆筒,转动圆筒,从3D打印针筒内挤出溶液B,打印到圆筒表面,得血管支架样品;d、将血管支架样品烘干、冷却后,得血管支架成品。本发明既具有减少血管再狭窄、血栓形成、血管壁损概率的特点,又具有载药量高、药物有效均匀分布、释放时间长的特点。

Description

基于3D打印的丹参酮ⅡA血管支架的制备方法
技术领域
本发明涉及一种医用器械制备领域,特别是一种基于3D打印的丹参酮ⅡA血管支架的制备方法。
背景技术
近年来,随着人们生活水平的不断提高,心血管疾病已经成为人类健康的重大威胁,是导致人类死亡和致残的重要因素之一。随着血管内治疗技术的发展,血管内支架植入术已经成为了治疗心血管疾病最有效的方法之一。血管支架是指在管腔球囊扩张成形的基础上,在病变段置入内支架以达到支撑狭窄闭塞段血管,减少血管弹性回缩及再塑形,保持管腔血流通畅的目的。
丹参酮ⅡA(Manshinone IIA,TA)是唇形科植物丹参Salvia miltiorrhiza Bge.的干燥根及根茎中提取的脂溶性菲醌化合物,历史悠久,疗效显著,在我国临床用于扩张冠脉、扩张血管、抗血栓、改善微循环障碍、保护血管内皮细胞损伤等,但水溶性差,释放极为缓慢。
目前3D打印技术在国际上已开始被应用于器官模型的制造与手术分析策划、个性化组织工程支架材料和假体植入物的制造等方面,利用3D打印技术可以根据不同患者的CT、磁共振成像(MRI)等成像数据,快速制造个性化的组织工程支架材料,从而实现材料与患者病变部位的完美匹配。但是对于血管支架而言,材料要求和尺寸精度要求比较高,其中3D打印的PLA支架和金属支架应用临床治疗后,容易对机体造成二次刺激,带来不同程度的血小板聚集、新的血栓的形成、短期内引发血管壁再狭窄、造成血管壁损等问题;而在支架表面涂以肝素、氧化钛等物质,或覆以可降解或不可降解的聚合物薄膜,或涂抹或者添加抗凝血药物的覆膜支架,存在载药量低、不够均匀、涂抹的药物释放过快的问题。
因此,现有的3D打印成型的PLA血管支架或者金属血管支架,存在容易造成血管再狭窄、血栓形成、血管壁损的问题,在支架表面涂覆药物的方式,存在载药量低且不均匀、药物释放过快的问题。
发明内容
本发明的目的在于,提供一种基于3D打印的丹参酮ⅡA血管支架的制备方法。本发明既具有减少血管再狭窄、血栓形成、血管壁损概率的特点,又具有载药量高、药物有效均匀分布、释放时间长的特点。
本发明的技术方案:基于3D打印的丹参酮ⅡA血管支架的制备方法,包括以下步骤:
a、建模:用计算机建模软件设计血管支架的3D模型,得建模数据;
b、制备打印溶液:称取丹参酮IIA原料药400-1000mg,加5-20mL乙醇,在超声仪中溶解20-40min,得溶液A;另称取聚乳酸2-10g,与溶液A混合,并加入二氯甲烷30-80ml溶解,得溶液B;
c、3D打印血管支架:将建模数据输入3D打印机的程序中,将溶液B装入3D打印针筒,制备与血管内径大小一致的圆筒,转动圆筒,从3D打印针筒内挤出溶液B,打印到圆筒表面,得血管支架样品;
d、将血管支架样品经过烘干、冷却后,得血管支架成品。
前述的基于3D打印的丹参酮ⅡA血管支架的制备方法中,所述步骤b为,制备打印溶液:称取丹参酮IIA原料药450-550mg,加8-15mL乙醇,在超声仪中溶解25-35min,得溶液A;另称取聚乳酸4-7g,与溶液A混合,在不断搅拌下加入二氯甲烷40-60ml溶解,得溶液B。
前述的基于3D打印的丹参酮ⅡA血管支架的制备方法中,所述步骤b为,制备打印溶液:称取丹参酮IIA原料药500mg,加10mL乙醇,在超声仪中溶解30min,得溶液A;另称取聚乳酸5g,与溶液A混合,在不断搅拌下加入二氯甲烷50ml溶解,得溶液B。
前述的基于3D打印的丹参酮ⅡA血管支架的制备方法中,所述步骤c中,圆筒的转速为10-40r/min,3D打印针筒的打印针头为23G或者25G,压强是200-300MPa。
前述的基于3D打印的丹参酮ⅡA血管支架的制备方法中,所述步骤c中,圆筒的转速为20r/min,3D打印针筒的打印针头为25G,打印针头的外径为0.5mm,内径为0.25mm,压强是250MPa。
前述的基于3D打印的丹参酮ⅡA血管支架的制备方法中,所述步骤d为,将血管支架样品经过烘箱33-45℃干燥、冷却后,得血管支架成品。
前述的基于3D打印的丹参酮ⅡA血管支架的制备方法中,所述步骤d为,将血管支架样品经过烘箱37℃干燥、冷却后,得血管支架成品。
与现有技术相比,本发明在PLA中加入TA,使用3D打印技术成功构建了具有良好力学强度的含药血管支架,TA在PLA支架中有效均匀分布,载药量高达30.43%,792h仅释放了药物的6.44%。该心血管支架在植入生物体初期,有效支撑病变部位血管壁,避免血管急性回弹并维持其通畅之后,随着病变部位狭窄血管的血管功能的逐步重建与自我修复,支架在4-6个月内逐渐被降解吸收,毫无残留;并结合了TA扩张血管、抗凝血、抗血栓、改善微循环障碍、保护引起的血管内皮细胞损伤等作用,使血管的舒缩活动及血管内皮细胞功能恢复到正常的生理状态,减少由于血管内皮损伤所导致的血管再狭窄和血栓形成的发生概率,减少由于支架安装导致的血管内皮二次损伤,及进一步导致的血管再狭窄和血栓再形成,减少患者在接受血管支架治疗后,服用抗凝药物和抗血栓药物带来的经济负担,提高患者的生活质量。
因此,本发明既具有减少血管再狭窄、血栓形成、血管壁损概率的特点,又具有载药量高、药物有效均匀分布、释放时间长的特点。
附图说明
图1是实施例的血管支架成品图;
图2是25G的打印针头分别在10r/min、20r/min、30r/min、40r/min的圆筒转速下打印得到的血管支架样品图。
具体实施方式
下面结合实施例对本发明作进一步的说明,但并不作为对本发明限制的依据。
实施例
本发明中采用的各个药品为:
丹参酮IIA原料药(西安昊安公司,98%,批号:HXDST2A140110);
聚乳酸PLA(300KD,东莞市展阳高分子材料有限公司);
乙醇(分析纯,昆山金城试剂有限公司,批号:20190618);
二氯甲烷(分析纯,上海试四赫维化工有限公司);
本发明中采用的各个仪器为:
电子天平(FA2004B,上海佑科仪器仪表有限公司);
JN-3200D超声波清洗机(宁波江南仪器厂);
JJ-1精密电动搅拌器(江苏省金坛市鸿科仪器厂);
现有技术中的3D打印机和3D打印软件;
RC膜透析袋(Mw=8000-14000,MD34,北京solarbio有限公司);
UV-5800PC型紫外分光光度计(上海元析仪器有限公司)。
基于3D打印的丹参酮ⅡA血管支架的制备方法,包括以下步骤:
a、建模:用计算机建模软件设计血管支架的3D模型,得建模数据;
b、制备打印溶液:称取丹参酮IIA原料药500mg,加10mL乙醇,在超声仪中溶解30min,得溶液A;另称取聚乳酸5g,与溶液A混合,在不断搅拌下加入二氯甲烷50ml溶解,得溶液B;
c、3D打印血管支架:将建模数据输入3D打印机的程序中,将溶液B装入3D打印针筒,制备与血管内径大小一致的圆筒,转动圆筒,圆筒的转速为10-40r/min,从3D打印针筒内挤出溶液B,3D打印针筒的打印针头为25G,打印针头的外径为0.5mm,内径为0.25mm,压强是250MPa,因二氯甲烷的挥发性极强,打印针头的参数设计和压强设计,保证出料均匀性,打印到圆筒表面,得血管支架样品;
d、将血管支架样品经过烘箱37℃干燥、冷却后,得血管支架成品。血管支架成品如图1所示。制得的血管支架成品,表面光滑,网格状分明,间隙均匀、适度。载药量高达30.43%,载药均匀。
此外,还做了打印针头为25G时,圆筒转速分别为10r/min、20r/min、30r/min、40r/min的情况下打印得到的血管支架样品。如图2所示。图中从左向右依次是10r/min、20r/min、30r/min、40r/min的圆筒转速下打印得到的血管支架样品。
从图2中可以明显看出,25G的针头在20r/min的打印速度下打印得到的血管支架样品最好。

Claims (6)

1.基于3D打印的丹参酮ⅡA血管支架的制备方法,其特征在于:包括以下步骤:
a、建模:用计算机建模软件设计血管支架的3D模型,得建模数据;
b、制备打印溶液:称取丹参酮IIA原料药400-1000mg,加5-20mL乙醇,在超声仪中溶解20-40min,得溶液A;另称取聚乳酸2-10g,与溶液A混合,并加入二氯甲烷30-80ml溶解,得溶液B;
c、3D打印血管支架:将建模数据输入3D打印机的程序中,将溶液B装入3D打印针筒,3D打印针筒的打印针头为23G或者25G,制备与血管内径大小一致的圆筒,转动圆筒,圆筒的转速为10-40r/min,从3D打印针筒内挤出溶液B,压强是200-300MPa,打印到圆筒表面,得血管支架样品;
d、将血管支架样品经过烘干、冷却后,得血管支架成品。
2.根据权利要求1所述的基于3D打印的丹参酮ⅡA血管支架的制备方法,其特征在于:所述步骤b为,制备打印溶液:称取丹参酮IIA原料药450-550mg,加8-15mL乙醇,在超声仪中溶解25-35min,得溶液A;另称取聚乳酸4-7g,与溶液A混合,在不断搅拌下加入二氯甲烷40-60ml溶解,得溶液B。
3.根据权利要求2所述的基于3D打印的丹参酮ⅡA血管支架的制备方法,其特征在于:所述步骤b为,制备打印溶液:称取丹参酮IIA原料药500mg,加10mL乙醇,在超声仪中溶解30min,得溶液A;另称取聚乳酸5g,与溶液A混合,在不断搅拌下加入二氯甲烷50ml溶解,得溶液B。
4.根据权利要求1所述的基于3D打印的丹参酮ⅡA血管支架的制备方法,其特征在于:所述步骤c中,圆筒的转速为20r/min,3D打印针筒的打印针头为25G,打印针头的外径为0.5mm,内径为0.25mm,压强是250MPa。
5.根据权利要求1所述的基于3D打印的丹参酮ⅡA血管支架的制备方法,其特征在于:所述步骤d为,将血管支架样品经过烘箱33-45℃干燥、冷却后,得血管支架成品。
6.根据权利要求5所述的基于3D打印的丹参酮ⅡA血管支架的制备方法,其特征在于:所述步骤d为,将血管支架样品经过烘箱37℃干燥、冷却后,得血管支架成品。
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