CN114631934A - 一种可营造低氧微环境促急性创面早期愈合的敷料 - Google Patents
一种可营造低氧微环境促急性创面早期愈合的敷料 Download PDFInfo
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- CN114631934A CN114631934A CN202210249664.6A CN202210249664A CN114631934A CN 114631934 A CN114631934 A CN 114631934A CN 202210249664 A CN202210249664 A CN 202210249664A CN 114631934 A CN114631934 A CN 114631934A
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Abstract
本发明公开了一种可营造低氧微环境促急性创面早期愈合的敷料，包括敷料本体，所述敷料本体由基质、第一涂覆层和第二涂覆层共同构成，所述第一涂覆层涂覆在基质的底部，所述第二涂覆层涂覆在第一涂覆层的底部，所述基质为丝素蛋白纳米纤维膜，所述第一涂覆层为促细胞生长药物，所述第二涂覆层为抑菌药物，本发明通过将由丝素蛋白纳米纤维膜制备的基质与细胞生长药物、抑菌药物进行配合使用，共同构建生物敷料，丝素蛋白纤维之间形成的支架便于细胞的黏附与迁移，并且能够达到低氧的目的，同时通过细胞生长药物以及抑菌药物的配合，起到协同促进创面愈合的作用，有利于实际的应用。
Description
技术领域
本发明属于创面愈合敷料技术领域，具体为一种可营造低氧微环境促急性创面早期愈合的敷料。
背景技术
随着社会经济的发展和我国人口老龄化加速，除烧创伤等引起的急性创面外，各种疾病导致的慢性难愈合创面，如糖尿病足创面、压疮、血管性溃疡、癌性溃疡、特殊细菌感染性创面、痛风石创面、各种医源性创面等逐年增加，创面治疗最核心的问题是如何加快愈合，而除了传统意义上的皮片移植、皮瓣移植等修复技术外，近年来，创面微环境对愈合的影响越来越受到重视，国内外的文献研究表明，低氧是组织损伤和创面愈合中突出的微环境因素，是对早期创面正常愈合的关键刺激因素，在组织修复各关键环节的调节中起关键作用。
但是目前国内外低氧敷料还尚未应用于临床，仅有少量敷料用于实验，主要存在的问题是：一是低氧敷料如何固定于创面上，保证创面处于低氧环境；二是通过既往研究我们得知适度低氧可显著促进创面愈合，但临床上究，目前绝大部分国内外研究也仅做了完全缺氧与常氧状态的创面愈合的对照研究。
另外，创面的潮湿和温暖环境是细菌的理想繁殖条件，有效的抑菌成分能够尽量维持创面处于无菌或细菌可控状态，降低创面感染的风险，提高创面愈合的治疗。适度的促细胞生长成分能够促进上皮细胞的增殖和迁移，缩短创面愈合的时间。所以我们在敷料中加载了抑菌和促生长成分。
发明内容：
本发明的目的就在于为了解决上述问题而提供一种可营造低氧微环境促急性创面早期愈合的敷料，解决了背景技术中提到的问题。
为了解决上述问题，本发明提供了一种技术方案：
一种可营造低氧微环境促急性创面早期愈合的敷料，包括敷料本体，所述敷料本体由基质、第一涂覆层和第二涂覆层共同构成，所述第一涂覆层涂覆在基质的底部，所述第二涂覆层涂覆在第一涂覆层的底部，所述基质为丝素蛋白纳米纤维膜，所述第一涂覆层为细胞生长药物，所述第二涂覆层为抑菌药物。
作为优选，所述丝素蛋白纳米纤维膜是以天然蚕丝素蛋白为主要原料研制而成，具体为甲酸溶液处理的10％新鲜丝素蛋白溶液通过静电纺丝技术形成的丝素蛋白纳米纤维膜，可以营造创面的低氧微环境。
作为优选，所述细胞生长药物通过如下重量份的原料制备而成：决明子 3-9份、川芎2-8份、甘草4-6份、红花4-6份、海藻酸钠5-8份、水提蜂胶 8-12份、醋酸3-7份。
作为优选，所述抑菌药物通过如下重量份的原料制备而成：溶菌酶3-6 份、地锦草2-7份、五倍子4-6份、黄芩3-5份、紫苦参根6-7份、益母草 8-11份、金银花2-5份。
本发明的有益效果是：本发明通过将由丝素蛋白纳米纤维膜制备的基质与细胞生长药物、抑菌药物进行配合使用，共同构建生物敷料，丝素蛋白纤维之间形成的支架便于细胞的黏附与迁移，并且能够营造创面低氧微环境，同时通过细胞生长药物以及抑菌药物的配合，起到协同促进创面愈合的作用，有利于实际的应用。
附图说明：
为了易于说明，本发明由下述的具体实施及附图作以详细描述。
图1是本发明低氧敷料内部结构剖视图；
图2是本发明全层皮肤创面内氧分压测定示意图；
图3是本发明小鼠背部皮肤全层创面内氧分压测定实物图；
图4是本发明两组创面内前3天氧分压的测定示意图；
图5是本发明3组原代小鼠表皮细胞与敷料共培养的细胞活力检测示意图；
图6是本发明两组小鼠全层皮肤创面的愈合过程示意图；
图7是本发明两组小鼠全层皮肤创面的未愈率统计示意图；
图8是本发明两组小鼠全层皮肤创面第3天皮肤组织中PCNA的表达示意图；
图9是本发明两组小鼠全层皮肤创面第3天创周皮肤组织HE染色示意图；
图10是本发明两组小鼠全层皮肤创面第3天皮肤组织中PCNA的表达统计分析示意图；
图11是本发明两组小鼠全层皮肤创面第3天创缘上皮细胞爬行长度统计图。
图1中：1、敷料本体；11、基质；12、第一涂覆层；13、第二涂覆层。
具体实施方式：
如图1-11所示，本具体实施方式采用以下技术方案：
实施例：
一种可营造低氧微环境促急性创面早期愈合的敷料，包括敷料本体1，所述敷料本体1由基质11、第一涂覆层12和第二涂覆层13共同构成，所述第一涂覆层12涂覆在基质11的底部，所述第二涂覆层13涂覆在第一涂覆层12 的底部，所述基质11为丝素蛋白纳米纤维膜，同时基质11采用美国KCI公司的具有单项透气功能的半透明膜进行固定；所述第一涂覆层12为细胞生长药物，所述第二涂覆层13为抑菌药物。
其中，所述丝素蛋白纳米纤维膜是以天然蚕丝素蛋白为主要原料研制而成的丝素蛋白制作而成的，丝素蛋白是一种高纯度的蛋白质，其不含细胞、细胞器、其他蛋白、多糖、DNA或其他片段，其具有优异的力学特性，良好的生物相容性、可控的降解性，同时形态易塑、安全无毒、透气保湿，并且是一种多孔丝素膜。甲酸溶液处理后的10％新鲜丝素蛋白溶液通过静电纺丝技术形成的丝素蛋白纳米纤维膜，可以营造创面的低氧微环境。
其中，所述细胞生长药物通过如下重量份的原料制备而成：决明子3-9 份、川芎2-8份、甘草4-6份、红花4-6份、海藻酸钠5-8份、水提蜂胶8-12 份、醋酸3-7份。
其中，所述抑菌药物通过如下重量份的原料制备而成：溶菌酶3-6份、地锦草2-7份、五倍子4-6份、黄芩3-5份、紫苦参根6-7份、益母草8-11 份、金银花2-5份。
以下通过具体实施例来说明本发明的有益效果：
实施例一、
而为了达到不同的透氧程度，我们采用了甲酸溶液和甲醇溶液对不同浓度的丝蛋白溶液进行了处理，具体如下：
1、实验组(低氧膜)：为甲酸溶液处理的10％新鲜丝素蛋白溶液形成的膜。后将膜置于通风橱中待甲酸完全挥发后形成最终样品；
2、对照组(透氧膜)：为甲醇处理的7％新鲜丝蛋白溶液形成的膜，后经纯水浸泡将甲醇充分浸泡挥发完后形成最终样品。
实施例二、
低氧敷料性能检测：采用与创缘(小鼠创面)氧含量接近的体积分数2％氧气行体外实验，显示体积分数2％氧气可促进表皮细胞增殖和迁移。为了达到在体创面低氧的目的，采用10％的甲酸溶液溶解丝蛋白制作丝蛋白纳米纤维膜，为了使丝蛋白纳米纤维膜固定于创面，采用美国KCI公司的具有单项透气功能的半透明膜进行固定，同时采用了小鼠背部皮肤的全层缺损创面检测制作敷料的透氧性，如图3所示，左侧为甲酸处理的丝素蛋白纳米纤维膜，右侧采用了甲醇处理的丝素蛋白纳米纤维膜进行对照。
结果发现：丝蛋白纳米纤维膜创面的前3天的氧体积分数在1％-5％之间，接近于测定的小鼠创缘的氧体积分数，具体如图4所示。
实施例三、
材料的生物安全性检验：为了确保材料的生物安全性，将低氧膜、透氧膜分别与原代小鼠表皮细胞共培养于1640培养基中，用CCK-8检测各组细胞 12小时、24小时、48小时、72小时的细胞活力，用OD450的值表示。结果显示3组细胞在12小时、24小时、48小时、72小时的细胞活力均无明显统计学差异(p＞0.05)，具体如图5所示。
实施例四、
载体实验：采取小鼠背部皮肤全层缺损创面进行了自身对照进行实验，前3天贴敷料，3天后敞开于空气中，具体如图6所示，分别在第1，3，5， 7，9天对两组小鼠全层皮肤创面的未愈合率进行配对t检验，发现自第1，3， 5，7，9天低氧组小鼠创面的未愈率均较透氧组低，具有统计学差异(p＜0.05)，具体如图7所示。
同时提取第3天两组创面的组织蛋白，采用蛋白质印记法检测其PCNA(细胞增殖的指标之一)含量，发现低氧组中PCNA明显高于常氧组，另外也进行了组织切片HE染色，发现低氧组中上皮细胞迁移较常氧组快，具体如图8与图9所示，在第3天时提取两组小鼠创周皮肤组织蛋白，用蛋白质印记法检测其PCNA的表达，并进行配对t检验，我们发现低氧组中PCNA的表达较透氧组明显升高(p＜0.05)，具体如图10所示，通过配对t检验低氧组爬行长度较透氧组明显偏长(p＜0.05)，具体如图11所示，通过以上实验，我们得出该低氧敷料早期应用于急性创面中可以促进创面的愈合。
尽管已经示出和描述了本发明的实施例，对于本领域的普通技术人员而言，可以理解在不脱离本发明的原理和精神的情况下可以对这些实施例进行多种变化、修改、替换和变型，本发明的范围由所附权利要求及其等同物限定。
Claims (4)
1.一种可营造低氧微环境促急性创面早期愈合的敷料，其特征在于，包括敷料本体(1)，所述敷料本体(1)由基质(11)、第一涂覆层(12)和第二涂覆层(13)共同构成，所述第一涂覆层(12)涂覆在基质(11)的底部，所述第二涂覆层(13)涂覆在第一涂覆层(12)的底部，所述基质(11)为丝素蛋白纳米纤维膜，所述第一涂覆层(12)为细胞生长药物，所述第二涂覆层(13)为抑菌药物。
2.根据权利要求1所述的一种可营造低氧微环境促急性创面早期愈合的敷料，其特征在于，所述丝素蛋白纳米纤维膜是以天然蚕丝素蛋白为主要原料研制而成，具体为甲酸溶液处理的10％新鲜丝素蛋白溶液通过静电纺丝技术形成的丝素蛋白纳米纤维膜。
3.根据权利要求1所述的一种可营造低氧微环境促急性创面早期愈合的敷料，其特征在于，所述细胞生长药物通过如下重量份的原料制备而成：决明子3-9份、川芎2-8份、甘草4-6份、红花4-6份、海藻酸钠5-8份、水提蜂胶8-12份、醋酸3-7份。
4.根据权利要求1所述的一种可营造低氧微环境促急性创面早期愈合的敷料，其特征在于，所述抑菌药物通过如下重量份的原料制备而成：溶菌酶3-6份、地锦草2-7份、五倍子4-6份、黄芩3-5份、紫苦参根6-7份、益母草8-11份、金银花2-5份。
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| CN111097067A (zh) * | 2020-01-10 | 2020-05-05 | 温州医科大学 | 一种促伤口快速愈合的抗菌性医用敷料及其制备方法 |
| CN111632187A (zh) * | 2020-06-12 | 2020-09-08 | 安徽农业大学 | 一种生物可降解医用敷料及其制备方法 |
| CN112741927A (zh) * | 2020-07-07 | 2021-05-04 | 山东汉方制药有限公司 | 一种抗菌促愈合纳米纤维支架及采用该支架制得的纳米纤维支架贴 |
| CN112451732A (zh) * | 2020-11-27 | 2021-03-09 | 山东大学 | 一种单侧负载银的丝素蛋白抗菌敷料及制备方法和应用 |
| CN113769151A (zh) * | 2020-11-27 | 2021-12-10 | 山东大学 | 一种单侧负载银的丝素蛋白抗菌敷料及制备方法和应用 |
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