CN116036352B - 促进创面愈合的抗菌水凝胶粘合剂及其制备方法和应用 - Google Patents
促进创面愈合的抗菌水凝胶粘合剂及其制备方法和应用 Download PDFInfo
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- CN116036352B CN116036352B CN202310026256.9A CN202310026256A CN116036352B CN 116036352 B CN116036352 B CN 116036352B CN 202310026256 A CN202310026256 A CN 202310026256A CN 116036352 B CN116036352 B CN 116036352B
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- beta
- cyclodextrin
- hydrogel
- hydrogel adhesive
- glucan
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Abstract
本发明涉及促进创面愈合的抗菌水凝胶粘合剂及其制备方法和应用。首先将β‑葡聚糖酸解活化后与透明质酸反应,透析、干燥后得β‑葡聚糖接枝透明质酸,然后将聚乙烯醇和β‑环糊精通过分子间作用力产生氢键交联形成水凝胶粘合剂的基底,保障粘合剂的机械性能与粘附性,并加入β‑葡聚糖接枝透明质酸,形成互穿网络水凝胶,提高抗炎修复功能,有效促进伤口愈合并减少疤痕形成。最后以β‑环糊精为保护剂,用硼氢化钠还原硝酸银,形成银纳米粒子的胶体水溶液,透析后得到由β‑环糊精包裹的纳米银,将其添加到互穿网络水凝胶,进一步提高水凝胶的抗菌性能。
Description
技术领域
本发明涉及医用生物材料技术领域,具体涉及促进创面愈合的抗菌水凝胶粘合剂及其制备方法和应用。
背景技术
皮肤作为人体最大的器官,提供了抵御外界环境使机体免受生物侵扰的重要天然屏障。皮肤一旦受到损伤,不仅会出血,还很容易让病原体进入体内造成伤口感染,引起炎症甚至溃烂。针对皮肤创伤的护理和治疗的问题时,临床上常常使用手术缝合线、吻合器等对伤口进行封合。虽然该方法缝合牢固,但是操作复杂,容易留疤,并且缝合时会对伤口造成二次伤害,在拆线时也会带来一定的痛苦和不适。因此有必要开发一种医用粘合剂来代替传统的缝合方式将伤口粘连在一起。目前已有的粘合剂存在很多缺陷,比如α-氰基丙烯酸酯衍生物粘合剂虽然粘合强度很大,但是生物相容性差,容易引起伤口炎症反应。后来研制出的纤维蛋白胶有着良好的生物相容性和降解性,却因价格昂贵、制备时间长、存在潜在感染病毒风险限制了其使用。
发明内容
本发明提供了促进创面愈合的抗菌水凝胶粘合剂及其制备方法,以生物相容性好的聚乙烯醇、β-环糊精交联合成水凝胶粘合剂基底,加入接枝有透明质酸的β-葡聚糖,达到增强伤口修复率、提高皮肤修复度的效果,最后加入银纳米粒子,提高水凝胶粘合剂的抗菌性能。
本发明解决上述技术问题的方案如下:促进创面愈合的抗菌水凝胶粘合剂,它包括水凝胶互穿网络,所述水凝胶互穿网络负载有β-环糊精包裹的纳米银,β-环糊精包裹纳米银的负载量为0.02~2wt%;所述水凝胶互穿网络由聚乙烯醇和β-环糊精交联合成的水凝胶粘合剂基底、降解活化的β-葡聚糖接枝透明质酸组成;以所述水凝胶互穿网络为基准,所述水凝胶粘合剂基底的含量为98-99.9wt%;降解活化的β-葡聚糖接枝透明质酸的含量为0.1-2wt%。
由聚乙烯醇和β-环糊精交联合成水凝胶粘合剂基底保障粘合剂的机械性能与粘附性,降解活化的β-葡聚糖接枝透明质酸提高抗炎修复,β-环糊精包裹纳米银为纳米银粒子提供保护层防止氧化。
优选的,所述β-环糊精包裹纳米银的负载量为2wt%, 所述水凝胶粘合剂基底的含量为99.8wt%;降解活化的β-葡聚糖接枝透明质酸的含量为0.2wt%。
优选的,所述聚乙烯醇与β-环糊精质量之比0.5-5:1。
优选的,β-环糊精包裹纳米银溶液的粒子粒径为35-45nm。
上述促进创面愈合的抗菌水凝胶粘合剂的制备方法包括以下步骤:
S1、将β-葡聚糖进行降解再活化,得到降解活化的β-葡聚糖,降解后的β-葡聚糖纯度更高,分子量更低,提高与透明质酸的接枝率;降解活化步骤具体如下:取20~80mL甲酸、1~5g β-葡聚糖混合均匀,加热至75-100℃反应1-4h,40~100℃真空干燥甲酸至少量,加入20-50mL无水乙醇混合均匀,置换出葡聚糖并在4000~8000rpm的转速下离心10-30min,收集沉淀后冷冻干燥48~72h,得到降解后的β-葡聚糖,将β-葡聚糖溶于20~40mL超纯水中,加热至75-100℃反应1-3h,加入1~4mL环氧氯丙烷于20-60℃超声2-6h,40~100℃真空干燥液体至少量,加入20-50mL无水乙醇混合均匀,置换出葡聚糖并在4000~8000rpm的转速下离心10-30min,收集沉淀后冷冻干燥48~72h;
S2、将降解活化后的β-葡聚糖与透明质酸按照1:1-10的质量比加入到20-100mL超纯水中,于20~80℃反应48~60h,经过透析3~7天,将溶液冷冻干燥48~72h,得到β-葡聚糖接枝透明质酸;β-葡聚糖具有消炎、抗肿瘤、抗辐射和增强机体免疫功能等生物活性,提高巨噬细胞向伤口位置转移并促进胶原的沉积;透明质酸,具有良好的生物相容性、可降解性和极高的保水性,可以调控细胞的粘附、促进伤口愈合和血管化。
S3、取聚乙烯醇和β-环糊精分散于10~80mL超纯水中,再加入硼酸,加热至75-100℃搅拌反应1-4h,得到水凝胶粘合剂基底;在水凝胶粘合剂基底中加入β-葡聚糖接枝透明质酸,于30-60℃下搅拌反应0.5~3h,得到水凝胶互穿网络;其中,硼酸的加入量为所述水凝胶粘合剂的基底的1-3wt%,
S4、将浓度为10~100mM β-环糊精溶液与浓度为1~6mM硝酸银溶液混合搅拌1-6h,再以2~8s每滴的速度加入浓度为10~100mM硼氢化钠溶液于冰浴条件下反应,透析3-10天后,得到β-环糊精包裹纳米银(β-CD/AgNPs溶液)溶液,将β-环糊精包裹纳米银溶液加入至水凝胶互穿网络,搅拌反应,得到水凝胶粘合剂;其中,β-环糊精溶液、硝酸银溶液、硼氢化钠溶液的体积之比为1:0.5-2:0.5-2。
优选的,所述S2中,降解活化后的β-葡聚糖与透明质酸质量之比为1:5;透明质酸的纯度为90%~99%。
优选的,所述S3中,聚乙烯醇的醇解度为88%~99%,硼酸的加入量为所述水凝胶粘合剂的基底的2wt%。
优选的,所述S4中,β-环糊精溶液、硝酸银溶液、硼氢化钠溶液的体积之比为1:1:1。
优选的,所述S4中,所述β-环糊精溶液的浓度为50mM;硝酸银溶液浓度为6mM、硼氢化钠溶液浓度为50mM。
本发明还提供一种如上所述促进创面愈合的抗菌水凝胶粘合剂在医疗修复创面材料的应用。
本发明的有益效果是:
1、本发明选用的原材料生物相容性好,β-葡聚糖和透明质酸都是天然大分子多糖,来源广泛,价格低廉;聚乙烯醇、β-环糊精被认证为安全成分。
2、本发明通过β-葡聚糖接枝透明质酸结合两种材料的优点,改善了β-葡聚糖不溶于水、难降解与透明质酸机械强度差的缺点。使水凝胶粘合剂具有增加伤口愈合效率,促进成纤维细胞的聚集与粘附,并减少疤痕形成的等优点,且愈合效果优于普通手术缝合线。
3、本发明通过引入银纳米粒子,提高水凝胶粘合剂的抗菌性能,对大肠杆菌和金黄色葡萄球菌的杀菌率达到99.9%,可以有效预防细菌感染引起的炎症;在配合电刺激治疗时能增强细胞间的电信号传导,加快伤口愈合。
上述说明仅是本发明技术方案的概述,为了能够更清楚了解本发明的技术手段,并可依照说明书的内容予以实施,以下以本发明的较佳实施例并配合附图详细说明如后。本发明的具体实施方式由以下实施例及其附图详细给出。
附图说明
此处所说明的附图用来提供对本发明的进一步理解,构成本申请的一部分,本发明的示意性实施例及其说明用于解释本发明,并不构成对本发明的不当限定。在附图中:
图1为本发明实施例1、对比例1-2在搭接剪切力实验结果示意图;
图2为本发明实施例1与对比例1在抗菌实验(检测用菌为大肠杆菌)中菌落照片;
图3为本发明实施例1与对比例1在抗菌实验(检测用菌为金黄色葡萄球菌)中菌落照片;
图4为本发明实施例1与对比例1在细胞毒性实验结果示意图;
图5为本发明实施例1与对比例1在电刺激大鼠皮肤伤口模型的实验结果照片。
具体实施方式
以下结合附图对本发明的原理和特征进行描述,所举实例只用于解释本发明,并非用于限定本发明的范围。
本发明的工作原理:本发明首先将聚乙烯醇和β-环糊精通过分子间作用力产生氢键交联合成水凝胶粘合剂的基底,保障粘合剂的机械性能与粘附性,并加入β-葡聚糖和透明质酸,形成互穿网络水凝胶,提高抗炎修复功能,最后添加β-环糊精包裹的银纳米粒子,提高水凝胶的抗菌性能的同时配合电刺激治疗增强细胞间的电信号传导,从而促进血管生成及细胞增殖,加快伤口愈合的过程。水凝胶粘合剂在填充伤口的同时,可以作为介质将外界电信号传导到伤口所有部位,加快创伤修复过程。
实施例1
S1、称取2g β-葡聚糖溶于40mL甲酸溶液中,在90℃油浴锅中反应4h,90℃下真空干燥甲酸至少量,加入50mL无水乙醇置换出葡聚糖并在8000rpm的转速下离心10min,收集沉淀后冷冻干燥48h。将干燥后沉淀物加入到40mL的超纯水中,90℃反应2h,加入4mL的环氧氯丙烷进行活化,60℃超声6h,然后将溶液在90℃下真空干燥至少量液体,加入50mL无水乙醇后在8000rpm下离心20min,取沉淀冷冻干燥48h,得到降解活化后的β-葡聚糖。
S2、取0.8g葡聚糖和4g透明质酸加入到100mL超纯水中,在40℃的水浴锅中反应60h,然后透析7天,将溶液冷冻干燥72h,即制得β-葡聚糖接枝透明质酸。
S3、称取3g聚乙烯醇和2g β-环糊精,分散于80mL超纯水中,并加入硼酸作为交联剂,在90℃以上的水浴锅中加热搅拌3h后,得到水凝剂粘合剂基底,在基底中加入200mg中的β-葡聚糖接枝透明质酸,在60℃下水浴搅拌2h,即合成水凝胶互穿网络;以水凝胶互穿网络为基准;硼酸的加入量为2wt%。
S4、以β-环糊精为保护剂,硼氢化钠为还原剂,用化学还原法合成β-环糊精包裹银纳米粒子;将100mL、50mM的β-环糊精溶液加入100mL的6mM硝酸银溶液中,磁力搅拌6h后,加入200mL的50mM硼氢化钠溶液在冰水浴中还原,透析7天后,得到β-环糊精包裹的纳米银溶液;将制备好的β-环糊精包裹纳米银溶液按2wt%的比例加入到水凝胶互穿网络中,充分搅拌60min,得到负载纳米银的水凝胶粘合剂。
对比例1
对比例1与实施例1中的步骤相同,不同的在于不经过步骤S4的处理,得到无纳米银负载的水凝胶粘合剂。
对比例2
对比例2与对比例1中的步骤相同,不同的在于步骤S3中的聚乙烯醇加入量为1g,得到负载纳米银的水凝胶粘合剂。
将实施例与各对比例进行表征测试
1、搭接剪切力测试:取0.1g对比例1、2和实施例1制得的水凝胶粘合剂均匀涂在两个载玻片上,涂布面积分别为20mm×20mm,将两个载玻片搭接在一起,并在室温下放置12h。之后在室温下,使用万能力学测试机进行拉伸测试,拉伸速度为10mm/min。剪切强度=载玻片被拉开时的最大力/粘合面积。
结果如图1所示,对比例2粘合强度最低,对比例1和实施例1表现出接近的粘合强度,说明在水凝剂粘合剂基底合成中,聚乙烯醇比例偏低,会导致水凝胶粘合剂的粘性下降。
2、抗菌测试:
试验通过将菌液稀释涂布后计算菌落个数来表征材料的抗菌性能。
杀菌率%=(对照组CFU数-实验组CFU数)/(对照组CFU数)×100%
检测用菌:大肠杆菌(Escherichia coli ATCC25922),金黄色葡萄球菌(Staphylococcus aureus ATCC6538)。
分别将0.3g的实施例1和对比例1制得的水凝胶粘合剂灭菌后加入到含有2×106~2×108CFU/mL的大肠杆菌、金黄色葡萄球菌菌液的试管中,在37℃摇床里混合1~5h,之后用磷酸盐缓冲液(PBS,pH=7.4)稀释500倍,取100μL稀释液涂布到琼脂板上,置于37℃培养箱中培养12-24h,观察结果并计数菌落数。另设置一空白对照组,将含有2×106~2×108CFU/mL的大肠杆菌、金黄色葡萄球菌菌液的试管中,在37℃摇床里混合1~5h,之后用磷酸盐缓冲液(PBS,pH=7.4)稀释500倍,取100μL稀释液涂布到琼脂板上,置于37℃培养箱中培养12~24h,观察结果并计数菌落数。
结果如图2-3所示,对比例1的菌落数和空白组菌落数相比无明显变化,实施例1的菌落数明显减少。说明负载纳米银的水凝胶粘合剂具有抑菌效果。抗菌率整理如表1所示。
表1 实施例1和对比例1所得水凝胶粘合剂的抗菌率
项目 | 对比例1 | 实施例1 |
大肠杆菌抗菌率/% | 10.35 | 99.99 |
金黄色葡萄球菌抗菌率/% | 5.09 | 99.99 |
3、体外细胞毒性测试:先将的实施例1和对比例1制得的水凝胶粘合剂灭菌后以0.1g/mL的浓度浸泡在培养基24h,然后将成纤维细胞接种在96孔板中,接种密度为5000个/孔。将孔板放在37℃培养箱中培养24h后吸走培养基,将浸泡过水凝胶粘合剂的培养基转移到96孔板中,继续在培养箱中培养。24h后弃去培养基,用PBS缓冲液洗两遍后每孔避光加入含有MTT(噻唑蓝)和培养基的混合液,MTT和培养基的混合比例为1:9,37℃孵育4h后小心吸走上清液,每孔加入200μL的二甲基亚砜(DMSO)溶解孔板底部蓝紫色结晶,用酶标仪在490nm处检测吸光度。其中培养基为阴性对照组,含有10%苯酚的培养基混合液为阳性对照组。
结果如图4所示,可以看出对比例1和实施例1的细胞存活率分别为92.98%和95.32%,材料毒性等级为1级。
4、血液相容性测试:取抗凝血用生理盐水稀释,稀释比例为4:5,将实施例1和对比例1制得的水凝胶粘合剂分别浸泡在生理盐水中,37℃水浴半小时,然后添加稀释后的血样(0.2 mL 稀释血样/10mL生理盐水),接着在37℃的水浴锅中孵育1h,离心5min,取上清液用紫外分光光度计在545nm处测量吸光度。其中超纯水为阳性对照组,生理盐水为阴性对照组。结果如表2所示,实施例1与对比例1所制备的水凝胶粘合剂均达到了安全等级。
表2 实施例1和对比例1的水凝胶粘合剂的溶血实验结果
项目 | 对比例1 | 实施例1 |
溶血率/% | 1.8 | 2.3 |
结果(溶血率<5%,安全) | 安全 | 安全 |
5、抗炎修复功能测试:取实施例1中S2步骤得到的β-葡聚糖接枝透明质酸,灭菌后分别以0.02%、0.2%和2%的浓度浸泡在培养基24h,然后将成纤维细胞接种在96孔板中,接种密度为5000个/孔。将孔板放在37℃培养箱中培养24h后吸走培养基,将浸泡过材料后的培养基转移到96孔板中,继续在培养箱中培养。48h后弃去培养基,PBS缓冲液洗两遍后每孔避光加入含有MTT和培养基的混合液,MTT和培养基的混合比例为1:9,37℃孵育4h后小心吸走上清液,每孔加入200μL的二甲基亚砜(DMSO)溶解孔板底部蓝紫色结晶,用酶标仪在490nm处检测吸光度,并计算细胞增殖率,结果如表3所示。
表3 不同浓度的β-葡聚糖接枝透明质酸的细胞实验结果
浓度 | 0.02% | 0.2% | 2% |
细胞增殖率/%(n=3) | 110.2 | 125.2 | 95.5 |
6、电刺激细胞实验:将实施例1和对比例1制得的固定于24孔板底部,加入75%乙醇浸泡晾干,用PBS缓冲液充分清洗,加入培养基浸润24h,然后弃去培养基。将成纤维细胞接种在24孔板内的水凝胶上,接种密度为2000个/孔,待细胞贴壁生长在水凝胶上后进行电刺激,以培养基为对照组。48h后弃去培养基,每孔用PBS洗两遍后避光加入200μL CCK-8和培养基的混合液,CCK-8和培养基的混合比例为1:9,37℃孵育1h后取100μL于96孔板中,用酶标仪在450nm处检测吸光度,并计算细胞增殖率。结果如表3所示,说明在电刺激的情况下,负载有银纳米粒子的水凝胶粘合剂可增强细胞间的电信号传导,加快伤口愈合的过程。
表4 实施例1和对比例1的水凝胶粘合剂的电刺激细胞实验结果
项目 | 对比例1 | 实施例1 |
细胞增殖率/%(n=3) | 113.7 | 139.5 |
7、电刺激大鼠皮肤伤口模型的实验过程:大鼠麻醉后,对背部进行脱毛处理并用75%乙醇消毒,之后在背部创建三个1.5cm伤口,第一个伤口不进行处理作为空白对照组,第二个和第三个伤口分别用对比例1和实施例1制得的水凝胶粘结剂进行涂抹粘合,在100mV电压下进行半小时伤口电刺激愈合。结果如图5所示,经过实施例1水凝胶粘合剂处理的伤口愈合效果最好,负载有银纳米粒子的水凝胶粘合剂可增强细胞间的电信号传导,加快伤口愈合的过程。
以上所述,仅为本发明的较佳实施例而已,并非对本发明作任何形式上的限制;凡本行业的普通技术人员均可按说明书附图所示和以上所述而顺畅地实施本发明;但是,凡熟悉本专业的技术人员在不脱离本发明技术方案范围内,利用以上所揭示的技术内容而做出的些许更动、修饰与演变的等同变化,均为本发明的等效实施例;同时,凡依据本发明的实质技术对以上实施例所作的任何等同变化的更动、修饰与演变等,均仍属于本发明的技术方案的保护范围之内。
Claims (10)
1.促进创面愈合的抗菌水凝胶粘合剂,其特征在于,它包括水凝胶互穿网络,所述水凝胶互穿网络负载有β-环糊精包裹的纳米银,β-环糊精包裹纳米银的负载量为0.02~2wt%;所述水凝胶互穿网络由聚乙烯醇和β-环糊精交联合成的水凝胶粘合剂基底、降解活化的β-葡聚糖接枝透明质酸组成;以所述水凝胶互穿网络为基准,所述水凝胶粘合剂基底的含量为98-99.9wt%;降解活化的β-葡聚糖接枝透明质酸的含量为0.1-2wt%。
2.如权利要求1所述促进创面愈合的抗菌水凝胶粘合剂,其特征在于,所述β-环糊精包裹纳米银的负载量为2wt%,所述水凝胶粘合剂基底的含量为99.8wt%;降解活化的β-葡聚糖接枝透明质酸的含量为0.2wt%。
3.如权利要求1所述促进创面愈合的抗菌水凝胶粘合剂,其特征在于,β-环糊精包裹纳米银溶液的粒子粒径为35-45nm。
4.如权利要求1-3任一所述的促进创面愈合的抗菌水凝胶粘合剂的制备方法,其特征在于,包括以下步骤:
S1、将β-葡聚糖进行降解再活化,得到降解活化的β-葡聚糖;
S2、将降解活化后的β-葡聚糖与透明质酸按照1:1-10的质量比加入到超纯水中,于20~80℃反应48~60h,经过透析、冷冻干燥,得到β-葡聚糖接枝透明质酸;
S3、取聚乙烯醇和β-环糊精分散于超纯水中,再加入硼酸,加热至75-100℃搅拌反应1-4h,得到水凝胶粘合剂基底;在水凝胶粘合剂基底中加入β-葡聚糖接枝透明质酸,于30-60℃下搅拌反应0.5~3h,得到水凝胶互穿网络;其中,硼酸的加入量为所述水凝胶粘合剂的基底的1-3wt%;
S4、将浓度为10~100mMβ-环糊精溶液与浓度为1~6mM硝酸银溶液混合搅拌1-6h,再加入浓度为10~100mM硼氢化钠溶液于冰浴条件下反应,再经过透析得到β-环糊精包裹纳米银溶液,加入至水凝胶互穿网络,搅拌反应,得到水凝胶粘合剂;其中,β-环糊精溶液、硝酸银溶液、硼氢化钠溶液的体积之比为1:0.5-2:0.5-2。
5.如权利要求4所述促进创面愈合的抗菌水凝胶粘合剂的制备方法,其特征在于,所述S2中,降解活化后的β-葡聚糖与透明质酸质量之比为1:5;透明质酸的纯度为90%~99%。
6.如权利要求4所述促进创面愈合的抗菌水凝胶粘合剂的制备方法,其特征在于,所述S3中,所述聚乙烯醇与β-环糊精质量之比0.5-5:1。
7.如权利要求4所述促进创面愈合的抗菌水凝胶粘合剂的制备方法,其特征在于,所述S3中,聚乙烯醇的醇解度为88%~99%,硼酸的加入量为所述水凝胶粘合剂的基底的2wt%。
8.如权利要求4所述促进创面愈合的抗菌水凝胶粘合剂的制备方法,其特征在于,所述S4中,β-环糊精溶液、硝酸银溶液、硼氢化钠溶液的体积之比为1:1:1。
9.如权利要求4所述促进创面愈合的抗菌水凝胶粘合剂的制备方法,其特征在于,所述S4中,所述β-环糊精溶液的浓度为50mM;硝酸银溶液浓度为6mM、硼氢化钠溶液浓度为50mM。
10.如权利要求1-3任一所述促进创面愈合的抗菌水凝胶粘合剂在医疗修复创面材料的应用。
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1547488A (zh) * | 2001-06-29 | 2004-11-17 | 具有气味控制性能的高吸水性含羧基聚合物 | |
TW201510042A (zh) * | 2013-05-15 | 2015-03-16 | Evonik Industries Ag | 具快速吸收性質的超吸收性聚合物及其製造方法 |
CN108149485A (zh) * | 2017-12-13 | 2018-06-12 | 天津宝兴威科技股份有限公司 | 一种β-环糊精纳米银抗菌织物的制备方法 |
CN110339820A (zh) * | 2019-07-18 | 2019-10-18 | 苏州火睿新材料科技有限公司 | 一种载氧化高银的环糊精聚合微球及其制备方法 |
KR20200109254A (ko) * | 2019-03-12 | 2020-09-22 | 단국대학교 산학협력단 | 금 나노 입자 및 pva/베타-사이클로덱스트린을 포함하는 투명 나노섬유 하이드로겔 및 이의 제조방법 |
CN114099420A (zh) * | 2021-11-29 | 2022-03-01 | 长春工业大学 | 一种双层药物缓释水凝胶敷料的结构设计及其制备方法 |
CN114796620A (zh) * | 2022-04-24 | 2022-07-29 | 广东顺德工业设计研究院(广东顺德创新设计研究院) | 一种用作医用植入材料的互穿网络水凝胶及其制备方法和应用 |
-
2023
- 2023-01-09 CN CN202310026256.9A patent/CN116036352B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1547488A (zh) * | 2001-06-29 | 2004-11-17 | 具有气味控制性能的高吸水性含羧基聚合物 | |
TW201510042A (zh) * | 2013-05-15 | 2015-03-16 | Evonik Industries Ag | 具快速吸收性質的超吸收性聚合物及其製造方法 |
CN108149485A (zh) * | 2017-12-13 | 2018-06-12 | 天津宝兴威科技股份有限公司 | 一种β-环糊精纳米银抗菌织物的制备方法 |
KR20200109254A (ko) * | 2019-03-12 | 2020-09-22 | 단국대학교 산학협력단 | 금 나노 입자 및 pva/베타-사이클로덱스트린을 포함하는 투명 나노섬유 하이드로겔 및 이의 제조방법 |
CN110339820A (zh) * | 2019-07-18 | 2019-10-18 | 苏州火睿新材料科技有限公司 | 一种载氧化高银的环糊精聚合微球及其制备方法 |
CN114099420A (zh) * | 2021-11-29 | 2022-03-01 | 长春工业大学 | 一种双层药物缓释水凝胶敷料的结构设计及其制备方法 |
CN114796620A (zh) * | 2022-04-24 | 2022-07-29 | 广东顺德工业设计研究院(广东顺德创新设计研究院) | 一种用作医用植入材料的互穿网络水凝胶及其制备方法和应用 |
Non-Patent Citations (1)
Title |
---|
葡聚糖作为新型医用敷料的应用研究与前景;王小林 等;中国组织工程研究;第21卷(第26期);4252-4257 * |
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