CN113384738A - 一种促进伤口愈合的维甲酸敷料的制备方法 - Google Patents

一种促进伤口愈合的维甲酸敷料的制备方法 Download PDF

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CN113384738A
CN113384738A CN202110649176.XA CN202110649176A CN113384738A CN 113384738 A CN113384738 A CN 113384738A CN 202110649176 A CN202110649176 A CN 202110649176A CN 113384738 A CN113384738 A CN 113384738A
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tretinoin
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刘文婷
史宁
刘洪亮
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Shandong Liangfu Pharmaceutical Co ltd
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Abstract

本发明涉及伤口治疗领域,具体涉及一种促进伤口愈合的维甲酸敷料的制备方法,将天然抗菌消炎剂蜂胶与维甲酸联合使用,将可以有效促进伤口中形成有序的胶原交联纤维,提高伤口愈合速率;本敷料是一种泡沫形式的伤口敷料,能够保留大量的液体,可控释放生物活性剂,具有长时间的药物释放,提供长效的抗菌保护。

Description

一种促进伤口愈合的维甲酸敷料的制备方法
技术领域
本发明涉及伤口治疗领域,具体涉及一种促进伤口愈合的维甲酸敷料的制备方法。
背景技术
伤口愈合一般分为四个阶段:(1)止血;(2)炎症阶段,主要作用于清除细菌和清除碎屑,为组织生长做准备;(3)增殖阶段,肉芽组织填充伤口床,形成新的血管,收缩伤口,产生上皮细胞覆盖伤口;(4)成熟阶段,胶原纤维重新组织,恢复力量和灵活性。
伤口敷料提供一个湿润的保护屏障,能够阻止感染和污染,而且易于使用和更换。但目前均存在生物相容性差、不能有效预防伤口感染、促进伤口愈合速度缓慢等问题,在应用上具有很大的局限性。因此,需要开发一种兼具抗菌消炎和促进伤口愈合的多功能生物医用敷料。
很多天然物质具有抗菌消炎等功效,可以被用来加速伤口愈合,避免感染。蜂胶就是其中之一,蜂胶由树脂、蜡、花粉、多酚和精油组成,可以通过调炎性转录因子NF-κB和相关炎性因子来加速小鼠伤口愈合,同时具有抗菌、抗氧化、和抗炎症功效。但是此类抗菌、消炎试剂对组织和纤维增生并无明显促进作用,所以导致伤口愈合较慢。
维甲酸(维A酸),是体内维生素A的代谢中间产物,当皮肤发生生理性老化、或受药物、紫外线辐射及创伤伤害时,维甲酸可纠正或预防有害因素对真皮***生化成分及形态结构引起的异常,刺激皮肤细胞外基质蛋白合成,在真皮上部加速形成新的***带,并可提高伤口部位的张力强度。维甲酸对正常皮肤胶原合成无影响。此外,维甲酸对白细胞趋化有抑制活性,从而起到抗炎作用。而且全反式维甲酸对皮脂腺及其分泌无直接影响。
所以将天然抗菌消炎剂与维甲酸联合使用,将可以有效促进伤口中形成有序的胶原交联纤维,提高伤口愈合速率。
发明内容
为了解决以上问题,本发明提供了一种促进伤口愈合的维甲酸敷料的制备方法,将天然抗菌消炎剂蜂胶与维甲酸联合使用,将可以有效促进伤口中形成有序的胶原交联纤维,提高伤口愈合速率;本敷料是一种泡沫形式的伤口敷料,能够保留大量的液体,可控释放生物活性剂。
本发明具体采用的技术方案是:
一种促进伤口愈合的维甲酸敷料的制备方法,包括以下步骤:
S1:将反应量聚乙烯醇溶于95℃蒸馏水中,搅拌至溶解,然后冷却至室温,得到聚乙烯醇溶液;
本步骤所得聚乙烯溶液中,聚乙烯醇的浓度为4%(v/v)。
S2:将反应量海藻酸钠溶于40℃蒸馏水中,搅拌至溶解,然后冷却至室温,得到海藻酸钠溶液;
本步骤所得海藻酸钠溶液中,海藻酸钠的浓度为4%(v/v)。
S3:将所得聚乙烯醇溶液与海藻酸钠溶液按体积比1-3:1混合,搅拌至均一,得到基料溶液;
S4:将反应量维甲酸、蜂胶和活化剂混合溶解;
本步骤中,维甲酸、蜂胶和活化剂的用量为质量比16-20:1-2:20-22。
优选的,维甲酸、蜂胶和活化剂的用量为质量比16:1:20。
S5:将S3所得基料溶液加入S4中的混合物质,搅拌至均一;
S6:加入盐酸调节pH值降低至2,再加入戊二醛,缓慢搅拌,得到敷料溶液;
本步骤所得敷料溶液中,戊二醛的用量为0.075%(v/v)。
S7:将敷料溶液导入模具,-80℃冷冻(0.5-5h)后,在-50℃冻干24h,得到泡沫形式的敷料。
有益效果:
1)本发明将天然抗菌消炎剂与维甲酸联合使用,不仅可以消灭伤口处细菌,避免感染,还可以有效促进伤口中形成有序的胶原交联纤维,提高伤口愈合速率。
2)泡沫形式的伤口敷料,能够保留大量的液体,可控释放生物活性剂;具有长时间的药物释放,提供长效的抗菌保护。
附图说明
图1是各实施例与对照例的孔隙率柱状图。
图2是各实施例的溶胀速率折线图。
图3是各实施例的蜂胶释放率折线图。
图4是各实施例的维甲酸释放率折线图。
具体实施方式
下面是结合附图和实施例对本发明进一步说明。
实施例1
(1)将聚乙烯醇溶于95℃蒸馏水,使其浓度达到4%(v/v),搅拌至溶解,然后冷却至室温;
(2)将海藻酸钠溶于40℃蒸馏水,使其浓度达到4%(V/V),搅拌使其溶解,然后冷却至室温。
(3)在烧杯中按照1:1混合聚乙烯醇溶液和海藻酸钠溶液,搅拌至均一。
(4)在一个新的烧杯中,加入8g的吐温80、0.5g的维甲酸和10g的蜂胶,避免光照,搅拌使其溶解。
(5)向步骤4烧杯中分别加入混合好的聚乙烯醇和海藻酸钠溶液100ml,搅拌至均一。
(6)加入盐酸,将pH降低至2,再加入0.75%的戊二醛,缓慢搅拌30min。
(7)将溶液导入硅模具中,-80℃冷冻0.5h,在-50℃冻干24h,得到泡沫形式的敷料。
实施例2
(1)将聚乙烯醇溶于95℃蒸馏水,使其浓度达到4%(v/v),搅拌至溶解,然后冷却至室温;
(2)将海藻酸钠溶于40℃蒸馏水,使其浓度达到4%(V/V),搅拌使其溶解,然后冷却至室温。
(3)在烧杯中按照2:1混合聚乙烯醇溶液和海藻酸钠溶液,搅拌至均一。
(4)在一个新的烧杯中,加入8g的吐温80、0.5g的维甲酸和10g的蜂胶,避免光照,搅拌使其溶解。
(5)向步骤4烧杯中分别加入混合好的聚乙烯醇和海藻酸钠溶液100ml,搅拌至均一。
(6)加入盐酸,将pH降低至2,再加入0.75%的戊二醛,缓慢搅拌30min。
(7)将溶液导入硅模具中,-80℃冷冻1h,在-50℃冻干24h,得到泡沫形式的敷料。
实施例3
(1)将聚乙烯醇溶于95℃蒸馏水,使其浓度达到4%(v/v),搅拌至溶解,然后冷却至室温;
(2)将海藻酸钠溶于40℃蒸馏水,使其浓度达到4%(V/V),搅拌使其溶解,然后冷却至室温。
(3)在烧杯中按照3:1混合聚乙烯醇溶液和海藻酸钠溶液,搅拌至均一。
(4)在一个新的烧杯中,加入8g的吐温80、0.5g的维甲酸和10g的蜂胶,避免光照,搅拌使其溶解。
(5)向步骤4烧杯中分别加入混合好的聚乙烯醇和海藻酸钠溶液100ml,搅拌至均一。
(6)加入盐酸,将pH降低至2,再加入0.75%的戊二醛,缓慢搅拌30min。
(7)将溶液导入硅模具中,-80℃冷冻2h,在-50℃冻干24h,得到泡沫形式的敷料。
对照例1
(1)将聚乙烯醇溶于95℃蒸馏水,使其浓度达到4%(v/v),搅拌至溶解,然后冷却至室温;
(2)将海藻酸钠溶于40℃蒸馏水,使其浓度达到4%(V/V),搅拌使其溶解,然后冷却至室温。
(3)在烧杯中按照1:1混合聚乙烯醇溶液和海藻酸钠溶液,搅拌至均一。
(4)在一个新的烧杯中,加入8g的吐温80,避免光照,搅拌使其溶解。
(5)向步骤4烧杯中分别加入混合好的聚乙烯醇和海藻酸钠溶液100ml,搅拌至均一。
(6)加入盐酸,将pH降低至2,再加入0.75%的戊二醛,缓慢搅拌30min。
(7)将溶液导入硅模具中,-80℃冷冻0.5h,在-50℃冻干24h,得到泡沫形式的单一敷料。
对照例2
(1)将聚乙烯醇溶于95℃蒸馏水,使其浓度达到4%(v/v),搅拌至溶解,然后冷却至室温;
(2)将海藻酸钠溶于40℃蒸馏水,使其浓度达到4%(V/V),搅拌使其溶解,然后冷却至室温。
(3)在烧杯中按照1:1混合聚乙烯醇溶液和海藻酸钠溶液,搅拌至均一。
(4)在一个新的烧杯中,加入8g的吐温80、0.5g的维甲酸,避免光照,搅拌使其溶解。
(5)向步骤4烧杯中分别加入混合好的聚乙烯醇和海藻酸钠溶液100ml,搅拌至均一。
(6)加入盐酸,将pH降低至2,再加入0.75%的戊二醛,缓慢搅拌30min。
(7)将溶液导入硅模具中,-80℃冷冻1h,在-50℃冻干24h,得到泡沫形式的单一敷料。
对照例3
(1)将聚乙烯醇溶于95℃蒸馏水,使其浓度达到4%(v/v),搅拌至溶解,然后冷却至室温;
(2)将海藻酸钠溶于40℃蒸馏水,使其浓度达到4%(V/V),搅拌使其溶解,然后冷却至室温。
(3)在烧杯中按照1:1混合聚乙烯醇溶液和海藻酸钠溶液,搅拌至均一。
(4)在一个新的烧杯中,加入8g的吐温80和10g的蜂胶,避免光照,搅拌使其溶解。
(5)向步骤4烧杯中分别加入混合好的聚乙烯醇和海藻酸钠溶液100ml,搅拌至均一。
(6)加入盐酸,将pH降低至2,再加入0.75%的戊二醛,缓慢搅拌30min。
(7)将溶液导入硅模具中,-80℃冷冻2h,在-50℃冻干24h,得到泡沫形式的空白敷料。
按以下方法测试各实施例及对照例的孔隙率:
用乙醇置换法测试孔隙率,通过下面公式计算得到孔隙率P:
Figure BDA0003110449520000071
其中Wi是材料的初始质量,Wf是乙醇饱和处理后样品的质量,Vi是样品初始体积,ρ是纯乙醇的密度,约为0.789g/ml。试验独立重复三次。
测试结果如图1所示。
实施例1-3和对照例1-3均具有较高的孔隙率,所以添加蜂胶或维甲酸不影响基材(聚乙烯醇和海藻酸钠)所形成的孔隙。实施例1-3的孔隙率达到80%以上,保证了良好的吸附性和透气性,敷料对伤口渗出液的吸收可以避免组织浸渍,因为渗出物中含有基质金属蛋白酶和其他生化成分,可能会降解生长中的组织。同时可以保持伤口湿润环境,促进伤口愈合。
按以下方法测试各实施例的溶胀速率和药物释放速率:
溶胀速率
溶胀率通过测量样品在单位时间内吸收PBS的最大量计算得到。简单地说,将样品放置在含有PBS的培养皿中。在确定的时间(如0.1分钟,0.25分钟等)后,用镊子收集海绵,用滤纸轻轻去除表面多余的水分。对样品进行称重并返回PBS溶液。试验独立重复三次。
测试结果如图2所示。
溶胀率反映出材料的吸水性能,实施例1-3均能吸附超过自身2倍重量的液体,说明具有良好的吸附性。溶胀速率和材料的亲疏水性相关,随着海藻酸钠比例的降低,材料的溶胀能力也会降低。
药物释放速率
药物释放利用Franz扩散池进行测量。在供体池中加入37℃5mL的PBS,模拟人体组织温度,接受池中含有30mLPBS。样品浸没在供体池中,每隔一定时间从接受池中吸取3mlPBS用量测量,并补回3ml新鲜的PBS到接受池中。蜂胶浓度通过测试溶液在299nm处的吸光度计算得到。
由于维甲酸水溶性差,所以在PBS中添加2%的吐温80,以促进维甲酸溶解。维甲酸浓度通过测试溶液在350nm处吸光度计算得到。
测试结果如图3和图4所示。
图3和图4分别为蜂胶和维甲酸的释放速率,实施例1-3均具有长时间的药物释放,提供长效的抗菌保护。

Claims (6)

1.一种促进伤口愈合的维甲酸敷料的制备方法,其特征在于,包括以下步骤:
S1:将反应量聚乙烯醇溶于95℃蒸馏水中,搅拌至溶解,然后冷却至室温,得到聚乙烯醇溶液;
S2:将反应量海藻酸钠溶于40℃蒸馏水中,搅拌至溶解,然后冷却至室温,得到海藻酸钠溶液;
S3:将所得聚乙烯醇溶液与海藻酸钠溶液按体积比1-3:1混合,搅拌至均一,得到基料溶液;
S4:将反应量维甲酸、蜂胶和活化剂混合溶解;
S5:将S3所得基料溶液加入S4中的混合物质,搅拌至均一;
S6:加入盐酸调节pH值降低至2,再加入戊二醛,缓慢搅拌,得到敷料溶液;
S7:将敷料溶液导入模具,-80℃冷冻0.5-5h后,在-50℃冻干24h,得到敷料。
2.根据权利要求1所述促进伤口愈合的维甲酸敷料的制备方法,其特征在于,S1聚乙烯醇溶液中,聚乙烯醇的浓度为4%(v/v)。
3.根据权利要求1所述促进伤口愈合的维甲酸敷料的制备方法,其特征在于,S2海藻酸钠溶液中,海藻酸钠的浓度为4%(v/v)。
4.根据权利要求1所述促进伤口愈合的维甲酸敷料的制备方法,其特征在于,S4中所述维甲酸、蜂胶和活化剂的用量为质量比16-20:1-2:20-22。
5.根据权利要求1或4所述促进伤口愈合的维甲酸敷料的制备方法,其特征在于,所述活化剂为吐温-80。
6.根据权利要求1所述促进伤口愈合的维甲酸敷料的制备方法,其特征在于,S6敷料溶液中,戊二醛的用量为0.075%(v/v)。
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