CN108969790B - 一种具有抗疤痕再生功能的可吸收型多孔医用敷料及其制备方法 - Google Patents
一种具有抗疤痕再生功能的可吸收型多孔医用敷料及其制备方法 Download PDFInfo
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- CN108969790B CN108969790B CN201810740926.2A CN201810740926A CN108969790B CN 108969790 B CN108969790 B CN 108969790B CN 201810740926 A CN201810740926 A CN 201810740926A CN 108969790 B CN108969790 B CN 108969790B
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- calcium alginate
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Abstract
本发明提供一种具有抗疤痕再生功能的可吸收型多孔医用敷料及其制备方法，包括以下步骤：将膨润土溶液高速搅拌，在漩涡处加入氯化钠粉末，搅拌均匀后，滴加海藻酸钠和氯化钙，恒温静置培养，得到含微米海藻酸钙晶体的膨润土凝胶；将含微米海藻酸钙晶体的膨润土凝胶加入乙醇中，快速搅拌分散后，过滤，离心洗涤，得到了微米海藻酸钙晶体；将微米海藻酸钙晶体浸入硝酸银溶液中，室温恒温1h后，过滤去除多余的银离子，加入到硼氢化钠溶液还原反应，得到负载纳米银的海藻酸钙微晶；将负载纳米银的海藻酸钙微晶加入到蚕丝蛋白溶液中，混合均匀后，滴加抗病毒剂，经冷冻干燥，得到具有抗疤痕再生功能的可吸收型多孔医用敷料。
Description
技术领域
本发明属于纺织医用材料技术领域，具体涉及一种具有抗疤痕再生功能的可吸收型多孔医用敷料及其制备方法。
背景技术
疤痕疙瘩是临床上常见的病理性疤痕，也称胶质疤痕，形成机理较为复杂，与细胞因子、细胞凋亡、细胞外基质及角质形成细胞等有关，且具有不断浸润生长的特性，手术治疗后复发率极高。此外，伤口愈合过程中形成疤痕疙瘩不仅会引起皮肤粘连，影响创面愈合的时间和效果，而且极大的影响美观，因此，如何使创面早起愈合并减少或避免疤痕遗留是人们关注的热点。
中国专利CN 107638587A公开的具有组织诱导功能的无疤痕再生医用敷料及其制备方法，将可吸收聚氨酯/聚酯/聚醚/聚氨基酸/聚赖氨酸/聚赖氨酸PU高分子材料经静电纺丝制备得到具有组织诱导功能的可吸收医用膜片，然后在可吸收医用膜片的表面均匀喷涂上硅凝胶，然后在硅凝胶的表面附着多孔的抗菌吸液层或者促进伤口愈合的材料，选用合适的透气膜作为背衬层，最后按顺序紧密贴合，冻干/晾干/烘干，得到形成具有组织诱导功能的无疤痕再生医用敷料。该方法制备的具有组织诱导功能的无疤痕再生医用敷料利用硅凝胶或聚二甲基硅氧烷类的有机硅材料修复疤痕，再与抗菌材料和促进伤口愈合材料复合，使医用敷料既能促进伤口愈合和减少生孩子无疤痕生成。中国专利CN 105536027A公开的一种能够降低组织张力的疤痕贴及其制备方法，该疤痕贴包括聚氨酯膜、医用敷料和隔离纸，其中医用敷料包括天然海藻酸钠、羧甲基纤维素钠、甘油、β-葡聚糖、表皮生长因子、D-泛醇/胶原蛋白/尿囊素促愈合修复剂、水溶性红没药醇/甘草酸二钾/野菊花提取液/芦荟提取液抗敏抗炎剂、神经酰胺/碳酸二辛脂/透明质酸/海藻提取物/芦荟提取物/霍霍巴油/角鲨烷/小麦胚芽油/羊毛脂保湿润肤剂、橄榄油/α-生育酚/维生素E醋酸酯/D-抗坏血酸钠/维生素C磷酸酯镁/番茄提取物/亚硫酸钠/二丁基羟基甲苯/花青素/辅酶Q10/葡萄籽提取物促愈合剂、乳化剂、植物抗菌剂、防腐剂、香精和水，该方法制备的疤痕贴可减少伤口组织张力，防止伤口张力稍大使伤口处纤维过渡增生形成疤痕疙瘩。由上述现有技术可知，通过将伤口舒缓材料和促进伤口愈合材料加入到医用敷料中，并与其他抗菌材料复合，以提高医用敷料的综合性，但是功能性材料多以大分子状态存在，皮肤吸收慢，且容易造成吸收不均，造成伤口恢复进度不均，既而容易形成较小的疤痕，效果仍有进一步提升的空间。
发明内容
本发明要解决的技术问题是提供一种具有抗疤痕再生功能的可吸收型多孔医用敷料及其制备方法，本发明将微米海藻酸钙晶体内部和表面形成银颗粒，再与抗病毒剂加入到蚕丝蛋白溶液中，经冷冻干燥制备得到多孔医用敷料，该方法制备的多孔医用敷料将微米技术与纳米技术结合，制备的多孔医用敷料透气吸收性好，还具有抗菌和抗疤痕再生功能，使用效果显著。
为解决上述技术问题，本发明的技术方案是：
一种具有抗疤痕再生功能的可吸收型多孔医用敷料的制备方法，包括以下步骤：
(1)将膨润土溶液高速搅拌，在漩涡处加入氯化钠粉末，搅拌均匀后，滴加海藻酸钠和氯化钙，恒温静置培养，得到含微米海藻酸钙晶体的膨润土凝胶；
(2)将步骤(1)制备的含微米海藻酸钙晶体的膨润土凝胶加入乙醇中，快速搅拌分散后，过滤，离心洗涤，得到了微米海藻酸钙晶体；
(3)将步骤(2)制备的微米海藻酸钙晶体浸入硝酸银溶液中，室温恒温1h后，过滤去除多余的银离子，加入到硼氢化钠溶液还原反应，得到负载纳米银的海藻酸钙微晶；
(4)将步骤(3)制备的负载纳米银的海藻酸钙微晶加入到蚕丝蛋白溶液中，混合均匀后，滴加抗病毒剂，经冷冻干燥，得到具有抗疤痕再生功能的可吸收型多孔医用敷料。
作为上述技术方案的优选，所述步骤(1)中，膨润土粉末和氯化钠粉末的质量比为35:20。
作为上述技术方案的优选，所述步骤(1)中，海藻酸钠和氯化钙的质量比为1:1。
作为上述技术方案的优选，所述步骤(2)中，恒温静置培养的温度为50-65℃，时间为25-40d，体系的pH值为7.5-8。
作为上述技术方案的优选，所述步骤(2)中，微米海藻酸钙晶体的粒径为250-800μm。
作为上述技术方案的优选，所述步骤(3)中，微米海藻酸钙晶体、硝酸银和硼氢化钠的摩尔比为1:0.1-0.2：0.35-0.42。
作为上述技术方案的优选，所述步骤(4)中，抗病毒剂为膦甲酸、异丙肌苷或者更昔洛韦。
作为上述技术方案的优选，所述步骤(4)中，负载纳米银的海藻酸钙微晶、蚕丝蛋白和抗病毒剂的质量比为1:15-25:0.7-0.9。
作为上述技术方案的优选，所述步骤(4)中，具有抗疤痕再生功能的可吸收型多孔医用敷料的孔隙率为25-40％，孔径尺寸为0.05-0.5mm。
作为上述技术方案的优选，所述的一种具有抗疤痕再生功能的可吸收型多孔医用敷料的制备方法制备的具有抗疤痕再生功能的可吸收型多孔医用敷料。
与现有技术相比，本发明具有以下有益效果：
(1)本发明制备的具有抗疤痕再生功能的可吸收型多孔医用敷料的功能材料为负载纳米银的海藻酸钙微晶和抗病毒剂，负载纳米银的海藻酸钙微晶是利用膨润土溶液作为海藻酸钙晶体的生成体系，在膨润土溶液中会出现很多晶核，利用氯化钠控制海藻酸钙的尺寸，制备得到海藻酸钙微晶，海藻酸钙具有很强的止血作用，吸附性强，将海藻酸钙制成微米级分散于医用敷料中，海藻酸钙微晶更有利于伤口的吸附，且不容易造成具备刺激过量，防止伤口形成疤痕疙瘩，此外，海藻酸钙微晶中含附着银纳米颗粒，可保证伤口的抗菌性能，再与抗病毒剂协同作用，对伤口进行抗菌抗病毒作用。此外，本发明制备的多孔医用敷料的主要才为多孔蚕丝蛋白材料，蚕丝蛋白生物相容性好，主要成分为氨基酸，可作为养料被伤口吸收，且舒适透气。
(2)本发明制备的具有抗疤痕再生功能的可吸收型多孔医用敷料可以解决伤口的快速吸收问题，止血抗菌，透气舒适，且胶质细胞被选择性消除，防止疤痕的再生，功能性佳。
具体实施方式
下面将结合具体实施例来详细说明本发明，在此本发明的示意性实施例以及说明用来解释本发明，但并不作为对本发明的限定。
实施例1：
(1)按照膨润土粉末和氯化钠粉末的质量比为35:20，将膨润土溶液高速搅拌，在漩涡处加入氯化钠粉末，搅拌均匀后，滴加质量比为1:1的海藻酸钠和氯化钙，调节体系的pH值为7.5，在50℃下恒温静置培养25d，得到含微米海藻酸钙晶体的膨润土凝胶。
(2)将含微米海藻酸钙晶体的膨润土凝胶加入乙醇中，快速搅拌分散后，过滤，离心洗涤，得到粒径为250-800μm的微米海藻酸钙晶体。
(3)按照微米海藻酸钙晶体、硝酸银和硼氢化钠的摩尔比为1:0.1：0.35，将微米海藻酸钙晶体浸入1g/L硝酸银溶液中，室温恒温1h后，过滤去除多余的银离子，加入到1moL/L的硼氢化钠溶液，在25℃下还原反应60min，得到负载纳米银的海藻酸钙微晶。
(4)按照负载纳米银的海藻酸钙微晶、蚕丝蛋白和抗病毒剂的质量比为1:15:0.7，将负载纳米银的海藻酸钙微晶加入到5wt％的蚕丝蛋白溶液中，混合均匀后，滴加抗病毒剂膦甲酸，经冷冻干燥，得到具有抗疤痕再生功能的可吸收型多孔医用敷料，其中，具有抗疤痕再生功能的可吸收型多孔医用敷料的孔隙率为25％，孔径尺寸为0.05-0.2mm。
实施例2：
(1)按照膨润土粉末和氯化钠粉末的质量比为35:20，将膨润土溶液高速搅拌，在漩涡处加入氯化钠粉末，搅拌均匀后，滴加质量比为1:1的海藻酸钠和氯化钙，调节体系的pH值为8，在65℃下恒温静置培养40d，得到含微米海藻酸钙晶体的膨润土凝胶。
(2)将含微米海藻酸钙晶体的膨润土凝胶加入乙醇中，快速搅拌分散后，过滤，离心洗涤，得到粒径为250-800μm的微米海藻酸钙晶体。
(3)按照微米海藻酸钙晶体、硝酸银和硼氢化钠的摩尔比为1:0.2：0.42，将微米海藻酸钙晶体浸入1.5g/L硝酸银溶液中，室温恒温1h后，过滤去除多余的银离子，加入到1moL/L的硼氢化钠溶液，在30℃下还原反应90min，得到负载纳米银的海藻酸钙微晶。
(4)按照负载纳米银的海藻酸钙微晶、蚕丝蛋白和抗病毒剂的质量比为1:25:0.9，将负载纳米银的海藻酸钙微晶加入到8wt％的蚕丝蛋白溶液中，混合均匀后，滴加抗病毒剂异丙肌苷，经冷冻干燥，得到具有抗疤痕再生功能的可吸收型多孔医用敷料，其中，具有抗疤痕再生功能的可吸收型多孔医用敷料的孔隙率为40％，孔径尺寸为0.3-0.5mm。
实施例3：
(1)按照膨润土粉末和氯化钠粉末的质量比为35:20，将膨润土溶液高速搅拌，在漩涡处加入氯化钠粉末，搅拌均匀后，滴加质量比为1:1的海藻酸钠和氯化钙，调节体系的pH值为7.8，在55℃下恒温静置培养35d，得到含微米海藻酸钙晶体的膨润土凝胶。
(2)将含微米海藻酸钙晶体的膨润土凝胶加入乙醇中，快速搅拌分散后，过滤，离心洗涤，得到粒径为250-800μm的微米海藻酸钙晶体。
(3)按照微米海藻酸钙晶体、硝酸银和硼氢化钠的摩尔比为1:0.12：0.38，将微米海藻酸钙晶体浸入1.3g/L硝酸银溶液中，室温恒温1h后，过滤去除多余的银离子，加入到1moL/L的硼氢化钠溶液，在28℃下还原反应75min，得到负载纳米银的海藻酸钙微晶。
(4)按照负载纳米银的海藻酸钙微晶、蚕丝蛋白和抗病毒剂的质量比为1:18:0.8，将负载纳米银的海藻酸钙微晶加入到6.5wt％的蚕丝蛋白溶液中，混合均匀后，滴加抗病毒剂更昔洛韦，经冷冻干燥，得到具有抗疤痕再生功能的可吸收型多孔医用敷料，其中，具有抗疤痕再生功能的可吸收型多孔医用敷料的孔隙率为29％，孔径尺寸为0.15-0.35mm。
实施例4：
(1)按照膨润土粉末和氯化钠粉末的质量比为35:20，将膨润土溶液高速搅拌，在漩涡处加入氯化钠粉末，搅拌均匀后，滴加质量比为1:1的海藻酸钠和氯化钙，调节体系的pH值为7.9，在60℃下恒温静置培养35d，得到含微米海藻酸钙晶体的膨润土凝胶。
(2)将含微米海藻酸钙晶体的膨润土凝胶加入乙醇中，快速搅拌分散后，过滤，离心洗涤，得到粒径为250-800μm的微米海藻酸钙晶体。
(3)按照微米海藻酸钙晶体、硝酸银和硼氢化钠的摩尔比为1:0.18：0.40，将微米海藻酸钙晶体浸入1.4g/L硝酸银溶液中，室温恒温1h后，过滤去除多余的银离子，加入到1moL/L的硼氢化钠溶液，在29℃下还原反应70min，得到负载纳米银的海藻酸钙微晶。
(4)按照负载纳米银的海藻酸钙微晶、蚕丝蛋白和抗病毒剂的质量比为1:23:0.75，将负载纳米银的海藻酸钙微晶加入到6.5wt％的蚕丝蛋白溶液中，混合均匀后，滴加抗病毒剂更昔洛韦，经冷冻干燥，得到具有抗疤痕再生功能的可吸收型多孔医用敷料，其中，具有抗疤痕再生功能的可吸收型多孔医用敷料的孔隙率为38％，孔径尺寸为0.3-0.45mm。
实施例5：
(1)按照膨润土粉末和氯化钠粉末的质量比为35:20，将膨润土溶液高速搅拌，在漩涡处加入氯化钠粉末，搅拌均匀后，滴加质量比为1:1的海藻酸钠和氯化钙，调节体系的pH值为7.5，在65℃下恒温静置培养25d，得到含微米海藻酸钙晶体的膨润土凝胶。
(2)将含微米海藻酸钙晶体的膨润土凝胶加入乙醇中，快速搅拌分散后，过滤，离心洗涤，得到粒径为250-800μm的微米海藻酸钙晶体。
(3)按照微米海藻酸钙晶体、硝酸银和硼氢化钠的摩尔比为1:0.2：0.35，将微米海藻酸钙晶体浸入1.5g/L硝酸银溶液中，室温恒温1h后，过滤去除多余的银离子，加入到1moL/L的硼氢化钠溶液，在25℃下还原反应90min，得到负载纳米银的海藻酸钙微晶。
(4)按照负载纳米银的海藻酸钙微晶、蚕丝蛋白和抗病毒剂的质量比为1:15:0.9，将负载纳米银的海藻酸钙微晶加入到5wt％的蚕丝蛋白溶液中，混合均匀后，滴加抗病毒剂膦甲酸，经冷冻干燥，得到具有抗疤痕再生功能的可吸收型多孔医用敷料，其中，具有抗疤痕再生功能的可吸收型多孔医用敷料的孔隙率为29％，孔径尺寸为0.1-0.25mm。
实施例6：
(1)按照膨润土粉末和氯化钠粉末的质量比为35:20，将膨润土溶液高速搅拌，在漩涡处加入氯化钠粉末，搅拌均匀后，滴加质量比为1:1的海藻酸钠和氯化钙，调节体系的pH值为8，在50℃下恒温静置培养40d，得到含微米海藻酸钙晶体的膨润土凝胶。
(2)将含微米海藻酸钙晶体的膨润土凝胶加入乙醇中，快速搅拌分散后，过滤，离心洗涤，得到粒径为250-800μm的微米海藻酸钙晶体。
(3)按照微米海藻酸钙晶体、硝酸银和硼氢化钠的摩尔比为1:0.1：0.42，将微米海藻酸钙晶体浸入1g/L硝酸银溶液中，室温恒温1h后，过滤去除多余的银离子，加入到1moL/L的硼氢化钠溶液，在30℃下还原反应60min，得到负载纳米银的海藻酸钙微晶。
(4)按照负载纳米银的海藻酸钙微晶、蚕丝蛋白和抗病毒剂的质量比为1:25:0.7，将负载纳米银的海藻酸钙微晶加入到5-8wt％的蚕丝蛋白溶液中，混合均匀后，滴加抗病毒剂膦甲酸、异丙肌苷或者更昔洛韦，经冷冻干燥，得到具有抗疤痕再生功能的可吸收型多孔医用敷料，其中，具有抗疤痕再生功能的可吸收型多孔医用敷料的孔隙率为32％，孔径尺寸为0.12-0.26mm。
经检测，实施例1-6制备的具有抗疤痕再生功能的可吸收型多孔医用敷料的抗菌性、疤痕生长情况和疤痕去除情况的结果如下所示：
| 实施例1 | 实施例2 | 实施例3 | 实施例4 | 实施例5 | 实施例6 | |
| 抗菌率(％) | 79 | 86 | 84 | 80 | 82 | 83 |
| 处理10d后疤痕生长率(％) | 3.6 | 5.9 | 5.0 | 4.8 | 3.9 | 4.2 |
| 处理10d后疤痕去除率(％) | 29 | 37 | 36 | 34 | 30 | 33 |
由上表可见，本发明制备的具有抗疤痕再生功能的可吸收型多孔医用敷料不仅具有透气性能和抗菌性能，还具有优异的抑制疤痕和去除疤痕的能力。
上述实施例仅例示性说明本发明的原理及其功效，而非用于限制本发明。任何熟悉此技术的人士皆可在不违背本发明的精神及范畴下，对上述实施例进行修饰或改变。因此，举凡所属技术领域中具有通常知识者在未脱离本发明所揭示的精神与技术思想下所完成的一切等效修饰或改变，仍应由本发明的权利要求所涵盖。
Claims (9)
1.一种具有抗疤痕再生功能的可吸收型多孔医用敷料的制备方法，其特征在于，包括以下步骤：
（1）将膨润土溶液高速搅拌，在漩涡处加入氯化钠粉末，搅拌均匀后，滴加海藻酸钠和氯化钙，恒温静置培养，得到含微米海藻酸钙晶体的膨润土凝胶；
（2）将步骤（1）制备的含微米海藻酸钙晶体的膨润土凝胶加入乙醇中，快速搅拌分散后，过滤，离心洗涤，得到了微米海藻酸钙晶体；
（3）将步骤（2）制备的微米海藻酸钙晶体浸入硝酸银溶液中，室温恒温1h后，过滤去除多余的银离子，加入到硼氢化钠溶液还原反应，得到负载纳米银的海藻酸钙微晶；微米海藻酸钙晶体、硝酸银和硼氢化钠的摩尔比为1:0.1-0.2：0.35-0.42；
（4）将步骤（3）制备的负载纳米银的海藻酸钙微晶加入到蚕丝蛋白溶液中，混合均匀后，滴加抗病毒剂，经冷冻干燥，得到具有抗疤痕再生功能的可吸收型多孔医用敷料。
2.根据权利要求1所述的一种具有抗疤痕再生功能的可吸收型多孔医用敷料的制备方法，其特征在于：所述步骤（1）中，膨润土粉末和氯化钠粉末的质量比为35:20。
3.根据权利要求1所述的一种具有抗疤痕再生功能的可吸收型多孔医用敷料的制备方法，其特征在于：所述步骤（1）中，海藻酸钠和氯化钙的质量比为1:1。
4.根据权利要求1所述的一种具有抗疤痕再生功能的可吸收型多孔医用敷料的制备方法，其特征在于：所述步骤（1）中，恒温静置培养的温度为50-65℃，时间为25-40d，体系的pH值为7.5-8。
5.根据权利要求1所述的一种具有抗疤痕再生功能的可吸收型多孔医用敷料的制备方法，其特征在于：所述步骤（2）中，微米海藻酸钙晶体的粒径为250-800μm。
6.根据权利要求1所述的一种具有抗疤痕再生功能的可吸收型多孔医用敷料的制备方法，其特征在于：所述步骤（4）中，抗病毒剂为膦甲酸、异丙肌苷或者更昔洛韦。
7.根据权利要求1所述的一种具有抗疤痕再生功能的可吸收型多孔医用敷料的制备方法，其特征在于：所述步骤（4）中，负载纳米银的海藻酸钙微晶、蚕丝蛋白和抗病毒剂的质量比为1:15-25:0.7-0.9。
8.根据权利要求1所述的一种具有抗疤痕再生功能的可吸收型多孔医用敷料的制备方法，其特征在于：所述步骤（4）中，具有抗疤痕再生功能的可吸收型多孔医用敷料的孔隙率为25-40%，孔径尺寸为0.05-0.5mm。
9.根据权利要求1-8任一项所述的一种具有抗疤痕再生功能的可吸收型多孔医用敷料的制备方法制备的有抗疤痕再生功能的可吸收型多孔医用敷料。
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