CN114849052A - 一种糖尿病皮肤创口修复微针贴片及其制备方法 - Google Patents
一种糖尿病皮肤创口修复微针贴片及其制备方法 Download PDFInfo
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- CN114849052A CN114849052A CN202210454782.0A CN202210454782A CN114849052A CN 114849052 A CN114849052 A CN 114849052A CN 202210454782 A CN202210454782 A CN 202210454782A CN 114849052 A CN114849052 A CN 114849052A
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- microneedle
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Abstract
本发明具体涉及一种糖尿病皮肤创口修复微针贴片及其制备方法,包括:(1)将生物相容性高分子与抗糖尿病药物混合,并与光引发剂完全溶解在溶剂中形成均匀混合溶液;(2)在过氧化钙表面包覆聚多巴胺获得功能性复合纳米粒子;(3)将功能性复合纳米粒子混入纺丝液中通过静电纺丝制得复合纤维膜;(4)在微针模板模腔上方滴加均匀混合溶液,填满模腔后去除模腔上方多余溶液;(5)将复合纤维膜附着于微针模板模腔上方,并利用紫外光辐射后在室温环境下干燥,得到微针贴片。本发明微针贴片的微针有效刺入皮肤,抗糖尿病药物得以释放,调节血糖浓度;复合纤维膜微针贴片具有光热转换、ROS清除和供氧性能等性能,能有效促进皮肤创口的修复。
Description
技术领域
本发明属于高分子微针制备技术领域,具体涉及一种糖尿病皮肤创口修复微针贴片及其制备方法。
背景技术
慢性糖尿病严重影响患者的生活质量,并且极易诱发并发症状(如肥胖症、糖尿病足溃烂等慢性疾病)。受高血糖浓度和基质金属蛋白酶(MMPs)的影响,慢性糖尿病伤口愈合缓慢,伤口创面产生持续性的炎症反应,造成血管和肉芽组织再生受阻。伤口长期暴露于环境中,极易导致细菌感染,使得病情进一步恶化。此外,慢性糖尿病伤口组织部位存在大量的炎症因子并产生过量的活性氧自由基(ROS),炎症因子加剧纤维细胞的凋亡。而过量的ROS将打破体内氧化应激的平衡,削弱机体抗氧化能力,对生长因子,核酸和周围正常组织产生严重影响,阻碍慢性糖尿病伤口愈合。
研究表明,氧气(O2)可促进细胞增殖和组织重塑。多种载氧治疗体系已被用于伤口修复。过氧化钙(CaO2)具有良好的生物相容性,可在弱酸性环境下与水反应生成O2。然而,纯无机纳米粒子难以黏附于组织表面,易引发皮肤组织的炎症反应。
发明内容
基于现有技术中存在的上述不足,本发明的目的是提供一种糖尿病皮肤创口修复微针贴片及其制备方法,通过静电纺丝的方法制备包含功能性复合纳米粒子的复合纳米纤维膜。此外,将抗糖尿病药物载入微针针头,通过微针模板和光聚合技术,使微针针头与复合纳米纤维膜连接,形成柔性皮肤创口修复微针贴片。该方法反应条件温和、简单易行、绿色无污染,所制备的柔性皮肤创口修复微针贴片敷料兼具血糖水平调控和皮肤创口修复的功能,特别适合于糖尿病患者皮肤溃疡的治疗应用。
为了达到上述发明目的,本发明采用如下技术方案:
一种糖尿病皮肤创口修复微针贴片的制备方法,包括以下步骤:
(1)将生物相容性高分子与抗糖尿病药物混合,并与光引发剂完全溶解在溶剂中形成均匀混合溶液,并超声除去气泡;
(2)在过氧化钙表面包覆聚多巴胺,获得功能性复合纳米粒子;
(3)将功能性复合纳米粒子混入纺丝液中,通过静电纺丝制得复合纤维膜;
(4)在微针模板模腔上方滴加步骤(1)得到的均匀混合溶液,填满模腔后去除模腔上方多余溶液;
(5)将复合纤维膜附着于微针模板模腔上方,并利用紫外光辐射后在室温环境下干燥,得到微针贴片。
作为优选方案,所述步骤(1)中,生物相容性高分子为甲基丙烯酸酐化明胶、透明质酸、氧化海藻酸钠中的一种或几种。
作为优选方案,所述步骤(1)中,抗糖尿病药物为胰岛素、二甲双胍、甲苯磺丁脲或罗格列酮。
作为优选方案,所述步骤(2)中,功能性复合纳米粒子为聚多巴胺包覆过氧化钙的纳米粒子或金属离子掺杂聚多巴胺包覆过氧化钙的纳米粒子。
作为优选方案,所述金属离子为Cu2+、Fe3+、Mn4+或Co2+。
作为优选方案,所述步骤(3)中,所述纺丝液的高聚物为聚乙烯吡咯烷酮、聚乙烯醇、聚己内酯、聚乳酸、透明质酸、海藻酸钠、壳聚糖、明胶、丝素蛋白中的一种或几种。
作为优选方案,所述步骤(3)中,功能性复合纳米粒子的含量相对纺丝液的高聚物为0.05-1.0wt%。
作为优选方案,所述步骤(3)中,静电纺丝的参数包括:电压为10-15kV、纺丝距离为10-20cm、接收装置转速为100-500rpm。
作为优选方案,所述步骤(5)中,紫外光辐射的工艺参数包括:紫外光波长为365nm、功率为10-100mW·cm-2、光辐射时间为3-10min。
本发明还提供一种如上任一方案所述的制备方法制得的糖尿病皮肤创口修复微针贴片。
与现有技术相比,本发明具有如下有益效果:
本发明的糖尿病皮肤创口修复微针贴片,微针有效刺入皮肤,使得微针的抗糖尿病药物得以释放,从而调节血糖浓度;复合纤维膜微针贴片具有光热转换、ROS清除和供氧性能等性能,能有效促进皮肤创口的修复;因此,本发明的糖尿病皮肤创口修复微针贴片兼具血糖水平调控和皮肤创口修复的双重功能,特别适合于糖尿病患者皮肤溃疡的治疗应用。
附图说明
图1为本发明实施例1的CaO2的SEM图;
图2为本发明实施例1的CaO2@PDA的SEM图;
图3为本发明实施例1的CaO2@PDA的TEM图;
图4为本发明实施例1的药物富集针尖示意图;
图5为本发明实施例1的微针贴片的照片以及SEM图;
图6为本发明实施例1的糖尿病动物模型的血糖值变化图;
图7为本发明实施例1的糖尿病动物模型的皮肤创口修复图;
图8为本发明实施例1的糖尿病动物模型的皮肤创口修复率图。
图9为本发明实施例6的药物富集针尖示意图。
具体实施方式
为了更清楚地说明本发明实施例,下面将对照附图说明本发明的具体实施方式。显而易见地,下面描述中的附图仅仅是本发明的一些实施例,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图,并获得其他的实施方式。
实施例1:
本实施例的微针贴片的制备方法,包括以下步骤:
(1)CaO2及CaO2@PDA纳米粒子的制备
在超声条件下,将1.0g CaCl2和0.2g PVP溶于无水乙醇中,形成均一溶液;随后加入10mL氨水溶液(0.8M)并不断搅拌,再将2.0mL H2O2(1.0M)缓慢注射至上述溶液中,并在室温下反应4h;将溶液置于离心管,在12,000rpm转速下离心收集沉淀,用无水乙醇洗涤三次,得到白色CaO2产物并分散于乙醇溶液中待使用。其中,如图1所示,CaO2为纳米球状结构。
随后将0.2g盐酸多巴胺溶于9.0mL乙醇/水溶液(v/v=3:1),缓慢滴加至上述CaO2乙醇溶液内并不断搅拌,同时加入2.0mL氨水溶液,反应12h,乙醇洗涤离心分离得到CaO2@PDA纳米粒子。其中,如图2和3所示,成功制得过氧化钙表面包覆聚多巴胺的CaO2@PDA功能性复合纳米粒子。
(2)微针复合纳米纤维贴片层的制备
将质量比为1:1的聚己内酯/明胶,按照20%(M/V)溶于10mL的六氟异丙醇溶剂(HFIP),同时加入10mg CaO2@PDA功能性复合纳米粒子,搅拌混合均匀,得到最终的纺丝液;其中,CaO2@PDA功能性复合纳米粒子的含量相对聚己内酯/明胶为1.0wt%;
调节静电纺丝参数,正极电压为12.0kV,负极电压为-2.0kV,纺丝距离为13cm,接收装置转速为200rpm,推进速度为0.08mL·min-1,制得复合纳米纤维膜。
(3)糖尿病皮肤创口修复微针贴片的制备
称取0.6g甲基丙烯酸酐化明胶,溶于2mL柠檬酸溶液中,溶解均匀后加入10mgIC2959和300mg胰岛素,混合搅拌溶解均匀,得到微针溶液;
借助移液枪将微针溶液浇铸至微针模具凹槽,随后去除微针PDMS模具凹槽表面多余的溶液,再将复合纳米纤维膜作为贴片层附着至PDMS模具的凹槽表面处,轻压后用再置于紫外光下(365nm、10mW·cm-2)照射10min,室温干燥12h,剥离模板即可,得到微针贴片,如图3所示,为药物富集针尖示意图,药物均匀分布在微针;如图4所示,本实施例成功制得微针贴片敷料。
以下对本实施例的糖尿病皮肤创口修复微针贴片在皮肤创口修复应用进行研究:
建立Ⅱ型糖尿病伤口小鼠模型,并分为对照组(control)、空白微针(即不含抗糖尿病药物)敷料组(MNs)、含抗糖尿病药物微针敷料组(MNs-D)、含抗糖尿病药物和功能性复合纳米粒子贴片层微针敷料组(MNs-D/F)以及含抗糖尿病药物和功能性复合纳米粒子贴片层微针敷料辅助近红外光组(MNs-D/F-NIR)。使用对应的微针敷料对糖尿病小鼠伤口进行治疗处理,其中对照组不做任何处理;分别在第1、3、5、7、10和14天,对小鼠的伤口进行数码成像,同时检测并记录小鼠血糖值。
对糖尿病小鼠血糖值进行测量,如图5所示,MNs-D、MNs-D/F和MNs-D/F-NIR组的血糖降低现象更为明显。此外,在第5天时,Control组的血糖出现回升现象,而MNs-D、MNs-D/F和MNs-D/F-NIR组的血糖值持续降低,并在第10天降低至9±3mM。在伤口愈合前7天内,与Control、MNs和MNs-D组的伤口状况相比较,MNs-D/F和MNs-D/F-NIR组的伤口面积出现明显降低的现象,如图6所示,伴随时间的进一步延长,在第10天对照组和MNs组的伤口面积出现较为明显的变化,但依然大于MNs-D/P和MNs-D/F-NIR组的伤口面积。这可能是Control、MNs和MNs-D组的糖尿病伤口处过量ROS产生的炎症反应,阻碍了伤口的愈合;在第14天时,MNs-D、MNs-D/F和MNs-D/F-NIR组的伤口几乎愈合完全,而Control和MNs组的伤口面积尚未愈合完整。伤口修复率如图7所示,MNs-D/F和MNs-D/F-NIR组在第7天的伤口修复率分别为59.5%和70%,而Control、MNs和MNs-D组的修复率分别为22.2%、23.3%和30.5%。在第14天,Control、MNs和MNs-D组的伤口愈合率分别为79.7%、82.5%和87.8%。而MNs-D/F和MNs-D/F-NIR组的伤口愈合率分别为94.7%和99.3%。
本实施例的糖尿病皮肤创口修复微针贴片的创口修复机理为:
聚多巴胺(PDA)具有优异的光热转换性能、生物相容性和组织黏附性能,可对纳米粒子材料的表面进行修饰。此外,PDA大分子链上的邻苯二酚官能团可与ROS结合,进而清除ROS。通过在CaO2纳米粒子的表面包覆PDA,制备得到具有光热转换、ROS清除和供氧性能的功能性复合纳米粒子,并将其负载于复合纳米纤维薄膜内,用于皮肤创口修复微针贴片敷料的柔性贴片层。此外,将抗糖尿病药物载入微针针头,得到柔性皮肤创口修复微针贴片敷料,实现糖尿病皮肤创口的快速修复应用。
实施例2:
本实施例的糖尿病皮肤创口修复微针贴片的制备方法,包括以下步骤:
(1)铜离子掺杂聚多巴胺包覆过氧化钙纳米粒子的制备(Cu-CaO2@PDA)
在超声条件下,将0.2g盐酸多巴胺和0.05g二水氯化铜溶于9.0mL乙醇/水溶液(v/v=3:1),缓慢滴加至上述在实施例1所制备的CaO2乙醇溶液中内并不断搅拌,同时加入2.0mL氨水溶液,反应12h,乙醇洗涤离心分离得到Cu-CaO2@PDA纳米粒子。
(2)微针复合纳米纤维贴片层的制备
将质量比为1:1的聚己内酯/透明质酸,按照15%(M/V)溶于10mL的六氟异丙醇溶剂(HFIP),同时加入5mg Cu-CaO2@PDA,搅拌混合均匀,得到纺丝液;其中,Cu-CaO2@PDA功能性复合纳米粒子的含量相对聚己内酯/透明质酸为0.5wt%;
调节静电纺丝参数,正极电压为15.0kV,负极电压为-3.0kV,纺丝距离20cm,接收装置转速为500rpm,推进速度为0.08mL·min-1,制得复合纳米纤维膜;
(3)皮肤创口修复高分子微针贴片的制备
称取0.6g甲基丙烯酸酐化透明质酸,溶于2mL丙酮中,溶解均匀后加入10mgIC2959和300mg甲苯磺丁脲,混合搅拌均匀;借助移液枪将溶液浇铸至微针模具凹槽;随后去除微针PDMS模具凹槽表面多余的溶液,再将微针复合纳米纤维贴片层附着至PDMS模具的凹槽表面处,轻压后用再置于紫外光下(365nm,20mW·cm-2)照射8min,室温干燥6h剥离模板即可。
实施例3:
本实施例的糖尿病皮肤创口修复微针贴片的制备方法,包括以下步骤:
(1)铁离子掺杂聚多巴胺包覆过氧化钙纳米粒子的制备(Fe-CaO2@PDA)
在超声条件下,将0.2g盐酸多巴胺和0.07g六水氯化铁溶于9.0mL乙醇/水溶液(v/v=3:1),缓慢滴加至上述在实施例1所制备的CaO2乙醇溶液中内并不断搅拌,同时加入1.5mL氨水溶液,反应15h,乙醇洗涤离心分离得到Fe-CaO2@PDA纳米粒子。
(2)微针复合纳米纤维贴片层制备:将质量比为1:1的聚乙烯醇/透明质酸,按照15%(M/V)溶于10mL的水中,同时加入8mg Fe-CaO2@PDA,搅拌混合均匀得到纺丝液;其中,Fe-CaO2@PDA功能性复合纳米粒子的含量相对聚乙烯醇/透明质酸为0.1wt%;
调节静电纺丝参数,正极电压为10.0kV,负极电压为-1.0kV,纺丝距离为10cm,接收装置转速为100rpm,推进速度为0.08mL·min-1,制得复合纳米纤维膜;
(3)皮肤创口修复高分子微针贴片的制备
称取0.3g甲基丙烯酸酐化透明质酸和0.3氧化海藻酸钠,溶于2mL去离子水中,溶解均匀后加入10mg IC2959和300mg罗格列酮,混合搅拌均匀;借助移液枪将溶液浇铸至微针模具凹槽;随后去除微针PDMS模具凹槽表面多余的溶液,再将微针复合纳米纤维贴片层附着至PDMS模具的凹槽表面处,轻压后用再置于紫外光下(365nm,30mW·cm-2)照射5min,室温干燥6h剥离模板即可。
实施例4:
本实施例的糖尿病皮肤创口修复微针贴片的制备方法,包括以下步骤:
(1)锰离子掺杂聚多巴胺包覆过氧化钙纳米粒子的制备(Mn-CaO2@PDA)
将0.2g盐酸多巴胺和0.08g四水合氯化锰溶于9.0mL乙醇/水溶液(v/v=3:1),缓慢滴加至上述在实施例1所制备的CaO2乙醇溶液中内并不断搅拌,同时加入2.5mL氨水溶液,反应6h,乙醇洗涤离心分离得到Mn-CaO2@PDA纳米粒子。
(2)微针复合纳米纤维贴片层的制备
将质量比为1:1的聚乙烯吡咯烷酮/丝素蛋白,按照10%(M/V)溶于10mL的水中,同时加入10mg Mn-CaO2@PDA,搅拌混合均匀得到纺丝液;其中,Mn-CaO2@PDA功能性复合纳米粒子的含量相对聚乙烯吡咯烷酮/丝素蛋白为0.05wt%;
调节静电纺丝参数,正极电压为11.0kV,负极电压为-1.0kV,纺丝距离为16cm,接收装置转速为300rpm,推进速度为0.08mL·min-1,制得复合纳米纤维膜;
(3)皮肤创口修复高分子微针贴片敷料的制备
称取0.3g甲基丙烯酸酐化丝素蛋白和0.3海藻酸钠,溶于2mL去离子水中,溶解均匀后加入10mg IC2959和300mg二甲双胍,混合搅拌均匀。借助移液枪将溶液浇铸至微针模具凹槽。随后去除微针PDMS模具凹槽表面多余的溶液,再将微针复合纳米纤维贴片层附着至PDMS模具的凹槽表面处,轻压后用再置于紫外光下(365nm,10mW·cm-2)照射5min,室温干燥6h剥离模板即可。
实施例5:
本实施例的糖尿病皮肤创口修复微针贴片的制备方法,包括以下步骤:
(1)钴离子掺杂聚多巴胺包覆过氧化钙纳米粒子的制备(Co-CaO2@PDA)
将0.2g盐酸多巴胺和0.10g六水合氯化钴溶于9.0mL乙醇/水溶液(v/v=3:1),缓慢滴加至上述在实施例1所制备的CaO2乙醇溶液中内并不断搅拌,同时加入2.5mL氨水溶液,反应6h,乙醇洗涤离心分离得到Co-CaO2@PDA纳米粒子。
(2)微针复合纳米纤维贴片层的制备
将质量比为1:1的丝素蛋白/壳聚糖,按照20%(M/V)溶于10mL的醋酸水溶液(0.1wt%)中,同时加入10mg Co-CaO2@PDA,搅拌混合均匀得到纺丝液;其中,Co-CaO2@PDA功能性复合纳米粒子的含量相对聚乙烯吡咯烷酮/丝素蛋白为0.25wt%;
调节静电纺丝参数,正极电压为14.0kV,负极电压为-3.0kV,纺丝距离为16cm,接收装置转速为300rpm,推进速度为0.08mL·min-1,制得复合纳米纤维膜;。调节静电纺丝参数,制备得到丝素蛋白/壳聚糖复合纳米纤维膜。
(3)皮肤创口修复高分子微针贴片敷料的制备
称取0.4g甲基丙烯酸酐化明胶和0.2聚乙烯醇,溶于2mL去离子水中,溶解均匀后加入10mg IC2959和300mg二甲双胍,混合搅拌均匀;借助移液枪将溶液浇铸至微针模具凹槽;随后去除微针PDMS模具凹槽表面多余的溶液,再将微针复合纳米纤维贴片层附着至PDMS模具的凹槽表面处,轻压后用再置于紫外光下(365nm,100mW·cm-2)照射3min,室温干燥6h剥离模板即可。
实施例6:
本实施例的微针贴片的制备方法与实施例1的不同之处在于:
在紫外光照射的过程中,进行离心处理,得到的微针贴片的微针部分内的药物在尖头聚集,如图9所示,从而有利于药物的释放,提升降血糖的效率;其中,离心转速不宜过高,过高的话药物聚集度高,微针针头的强度难以保证;离心转速不宜过低,过低的话难以使得药物聚集在针头部分;
其他步骤同实施例1。
鉴于本发明方案实施例众多,各实施例实验数据庞大众多,不适合于此处逐一列举说明,但是各实施例所需要验证的内容和得到的最终结论均接近。故而此处不对各个实施例的验证内容进行逐一说明,仅以实施例1-6作为代表说明本发明申请优异之处。
本文中所描述的具体实施例仅仅是对本发明精神作举例说明。本发明所属技术领域的技术人员可以对所描述的具体实施例做各种修改或补充或采用类似的方式替代,但并不会偏离本发明的精神或者超越所附权利要求书所定义的范围。
Claims (10)
1.一种糖尿病皮肤创口修复微针贴片的制备方法,其特征在于,包括以下步骤:
(1)将生物相容性高分子与抗糖尿病药物混合,并与光引发剂完全溶解在溶剂中形成均匀混合溶液,并超声除去气泡;
(2)在过氧化钙表面包覆聚多巴胺,获得功能性复合纳米粒子;
(3)将功能性复合纳米粒子混入纺丝液中,通过静电纺丝制得复合纤维膜;
(4)在微针模板模腔上方滴加步骤(1)得到的均匀混合溶液,填满模腔后去除模腔上方多余溶液;
(5)将复合纤维膜附着于微针模板模腔上方,并利用紫外光辐射后在室温环境下干燥,得到微针贴片。
2.根据权利要求1所述的制备方法,其特征在于,所述步骤(1)中,生物相容性高分子为甲基丙烯酸酐化明胶、透明质酸、氧化海藻酸钠中的一种或几种。
3.根据权利要求1所述的制备方法,其特征在于,所述步骤(1)中,抗糖尿病药物为胰岛素、二甲双胍、甲苯磺丁脲或罗格列酮。
4.根据权利要求1所述的制备方法,其特征在于,所述步骤(2)中,功能性复合纳米粒子为聚多巴胺包覆过氧化钙的纳米粒子或金属离子掺杂聚多巴胺包覆过氧化钙的纳米粒子。
5.根据权利要求4所述的制备方法,其特征在于,所述金属离子为Cu2+、Fe3+、Mn4+或Co2+。
6.根据权利要求1所述的制备方法,其特征在于,所述步骤(3)中,所述纺丝液的高聚物为聚乙烯吡咯烷酮、聚乙烯醇、聚己内酯、聚乳酸、透明质酸、海藻酸钠、壳聚糖、明胶、丝素蛋白中的一种或几种。
7.根据权利要求1所述的制备方法,其特征在于,所述步骤(3)中,功能性复合纳米粒子的含量相对纺丝液的高聚物为0.05-1.0wt%。
8.根据权利要求1所述的制备方法,其特征在于,所述步骤(3)中,静电纺丝的参数包括:电压为10-15kV、纺丝距离为10-20cm、接收装置转速为100-500rpm。
9.根据权利要求1所述的制备方法,其特征在于,所述步骤(5)中,紫外光辐射的工艺参数包括:紫外光波长为365nm、功率为10-100mW·cm-2、光辐射时间为3-10min。
10.一种如权利要求1-9任一项所述的制备方法制得的糖尿病皮肤创口修复微针贴片。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN110772500A (zh) * | 2019-11-08 | 2020-02-11 | 南昌大学 | 可发热的微针贴片及其制备方法和应用 |
Citations (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1961974A (zh) * | 2005-11-09 | 2007-05-16 | 中国科学院化学研究所 | 可生物降解及吸收的聚合物纳米纤维膜材料及其制备方法和用途 |
CN101172164A (zh) * | 2006-11-03 | 2008-05-07 | 中国科学院化学研究所 | 可生物降解及吸收的生物高分子纳米纤维膜材料及其制法和用途 |
US20080226699A1 (en) * | 2003-11-28 | 2008-09-18 | Acrux Dds Pty Ltd | Method and System for Rapid Transdermal Administration |
CN105944134A (zh) * | 2016-05-25 | 2016-09-21 | 东华大学 | 一种静电纺高壳聚糖含量的抗菌伤口敷料的制备方法 |
CN108837299A (zh) * | 2018-07-18 | 2018-11-20 | 武汉大学 | 一种智能调节血糖的微针贴片及其制备方法 |
CN110420344A (zh) * | 2019-07-16 | 2019-11-08 | 温州大学 | 一种伤口敷料及其制备方法与应用 |
CN110680929A (zh) * | 2019-09-18 | 2020-01-14 | 浙江大学 | 一种具有广谱活性氧清除功能的微球及其制备方法 |
CN112842989A (zh) * | 2021-01-20 | 2021-05-28 | 浙江理工大学 | 一种负载铜离子掺杂聚多巴胺的微针贴片及其制备方法、应用 |
CN112972699A (zh) * | 2021-03-02 | 2021-06-18 | 南京医科大学附属口腔医院 | 一种用于牙周调控的活性氧响应纳米药物载体及其制备方法 |
CN113041393A (zh) * | 2021-03-18 | 2021-06-29 | 苏州大学 | 可调控活性氧自由基的复合材料及其制备方法与应用 |
CN113577276A (zh) * | 2021-08-02 | 2021-11-02 | 浙江理工大学 | 一种离子掺杂聚多巴胺包覆过氧化钙复合纳米粒子及其制备方法与应用 |
CN113842396A (zh) * | 2021-10-12 | 2021-12-28 | 西安交通大学医学院第一附属医院 | 一种改性多聚多巴胺的抗氧化剂及应用 |
CN114159551A (zh) * | 2021-11-25 | 2022-03-11 | 西南交通大学 | 一种用于慢性创面修复的可溶性双层载药微针贴片及其制备方法 |
CN114225090A (zh) * | 2021-12-30 | 2022-03-25 | 南京大学 | 一种具有粘附性和抗菌性能的壳聚糖基纳米纤维伤口敷料及其制备方法 |
CN114344544A (zh) * | 2022-01-05 | 2022-04-15 | 四川大学 | 光激活抗菌敷料及其制备方法 |
CN114376993A (zh) * | 2022-02-16 | 2022-04-22 | 中南大学湘雅三医院 | 一种促进糖尿病人伤口愈合的载氧化酶微针及其制备方法 |
-
2022
- 2022-04-24 CN CN202210454782.0A patent/CN114849052A/zh active Pending
Patent Citations (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080226699A1 (en) * | 2003-11-28 | 2008-09-18 | Acrux Dds Pty Ltd | Method and System for Rapid Transdermal Administration |
CN1961974A (zh) * | 2005-11-09 | 2007-05-16 | 中国科学院化学研究所 | 可生物降解及吸收的聚合物纳米纤维膜材料及其制备方法和用途 |
CN101172164A (zh) * | 2006-11-03 | 2008-05-07 | 中国科学院化学研究所 | 可生物降解及吸收的生物高分子纳米纤维膜材料及其制法和用途 |
CN105944134A (zh) * | 2016-05-25 | 2016-09-21 | 东华大学 | 一种静电纺高壳聚糖含量的抗菌伤口敷料的制备方法 |
CN108837299A (zh) * | 2018-07-18 | 2018-11-20 | 武汉大学 | 一种智能调节血糖的微针贴片及其制备方法 |
CN110420344A (zh) * | 2019-07-16 | 2019-11-08 | 温州大学 | 一种伤口敷料及其制备方法与应用 |
CN110680929A (zh) * | 2019-09-18 | 2020-01-14 | 浙江大学 | 一种具有广谱活性氧清除功能的微球及其制备方法 |
CN112842989A (zh) * | 2021-01-20 | 2021-05-28 | 浙江理工大学 | 一种负载铜离子掺杂聚多巴胺的微针贴片及其制备方法、应用 |
CN112972699A (zh) * | 2021-03-02 | 2021-06-18 | 南京医科大学附属口腔医院 | 一种用于牙周调控的活性氧响应纳米药物载体及其制备方法 |
CN113041393A (zh) * | 2021-03-18 | 2021-06-29 | 苏州大学 | 可调控活性氧自由基的复合材料及其制备方法与应用 |
CN113577276A (zh) * | 2021-08-02 | 2021-11-02 | 浙江理工大学 | 一种离子掺杂聚多巴胺包覆过氧化钙复合纳米粒子及其制备方法与应用 |
CN113842396A (zh) * | 2021-10-12 | 2021-12-28 | 西安交通大学医学院第一附属医院 | 一种改性多聚多巴胺的抗氧化剂及应用 |
CN114159551A (zh) * | 2021-11-25 | 2022-03-11 | 西南交通大学 | 一种用于慢性创面修复的可溶性双层载药微针贴片及其制备方法 |
CN114225090A (zh) * | 2021-12-30 | 2022-03-25 | 南京大学 | 一种具有粘附性和抗菌性能的壳聚糖基纳米纤维伤口敷料及其制备方法 |
CN114344544A (zh) * | 2022-01-05 | 2022-04-15 | 四川大学 | 光激活抗菌敷料及其制备方法 |
CN114376993A (zh) * | 2022-02-16 | 2022-04-22 | 中南大学湘雅三医院 | 一种促进糖尿病人伤口愈合的载氧化酶微针及其制备方法 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110772500A (zh) * | 2019-11-08 | 2020-02-11 | 南昌大学 | 可发热的微针贴片及其制备方法和应用 |
CN110772500B (zh) * | 2019-11-08 | 2022-11-22 | 南昌大学 | 可发热的微针贴片及其制备方法和应用 |
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