CN108904530B - 一种纳米银杀菌止血组合物 - Google Patents
一种纳米银杀菌止血组合物 Download PDFInfo
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- CN108904530B CN108904530B CN201810876671.2A CN201810876671A CN108904530B CN 108904530 B CN108904530 B CN 108904530B CN 201810876671 A CN201810876671 A CN 201810876671A CN 108904530 B CN108904530 B CN 108904530B
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Abstract
本发明涉及一种生物医药技术领域,更具体地,本发明涉及一种纳米银杀菌止血组合物及其制备方法。本发明提供了一种纳米银杀菌止血组合物,所述杀菌止血组合的制备原料按重量份计算,至少包括以下组分:10~50份改性透明质酸、0.5~5份乳酸依沙吖啶、2~8份羧甲基壳聚糖接枝聚丙烯酸钠,其中,所述改性透明质酸包括有机组分和无机组分;所述无机组分包括纳米银和/钙离子。
Description
技术领域
本发明涉及一种生物医药技术领域,更具体地,本发明涉及一种纳米银杀菌止血组合物及其制备方法。
背景技术
出血是伴随着诸多病症出现的常见的急诊症状之一。过量失血可引起休克,危及病人生命。大量失血可降低病人对手术的耐受能力,影响术后恢复。同时,出血可严重影响手术视野,打乱组织层次,防碍技术操作,打乱手术步骤,分散手术者的精力,出血严重还会危及患者的生命。能否快速有效的止血,是治疗是否有效的一个关键因素。此外,在此过程中,杀菌以及创面的快速愈合对于皮肤的修复以及生命都有的很大的影响,随着医疗技术的不断发展和人民生活水平的提高,对用于伤口的医用材料提出了新的更高的要求。
目前,市场上开发的杀菌止血和促进伤口愈合的材料有很多,并且随着需求的不断提高,新型的医用功能性止血杀菌以及促进伤口愈合的材料也出现多种,由于其配方与制作工艺不同,其作用及应用范围也不尽相同,但其会存在不同的一些问题,例如,有的仅用于较浅的创面治疗,有的止血效果欠佳,换药后不能迅速止血止痛,给患者造成对换药的恐惧心里;有的容易黏附灰尘,也易黏附在衣物上;有的只局限于杀菌功能,即在配方中只有杀菌剂及辅料,而没有其他作用;有的止血杀菌以及促进伤口愈合的材料生物相容性较差;而有的纳米银或其他重金属医用材料,因金属材料分布不均,而造成局部重金属残留,对人体造成危害。
针对上述的一些问题,本发明提供一种纳米银杀菌止血组合物,该组合物含有纳米银,其与杀菌止血组合物体系具有协同的抗菌、抑菌作用;杀菌止血组合物可以促进血液凝固、促进创面快速愈合的作用,该止血杀菌组合物体能够有效保持伤口的湿润性,能够防止因医用材料的粘连而造成的二次创伤;此外,还可以吸收创面产生的大量渗透液,从而促进伤口愈合;该止血杀菌组合物有很好的生物相容性以及生物降解性能,减少了因排斥而带来的炎症反应。该止血杀菌组合物加工过程简单,易于工业化生产。
发明内容
本发明第一个方面提供了一种纳米银杀菌止血组合物,所述纳米银杀菌止血组合物的制备原料按重量份计算,至少包括以下组分:
改性透明质酸 10~50份;
乳酸依沙吖啶 0.5~5份;
羧甲基壳聚糖接枝聚丙烯酸钠 2~8份;
其中,所述改性透明质酸包括有机组分和无机组分;所述无机组分包括纳米银和/或钙离子。
作为本发明的一种优选技术方案,所述纳米银的制备原料与所述钙离子的制备原料的摩尔比为1:(2~5)。
作为本发明的一种优选技术方案,所述纳米银的制备原料包括银盐;所述钙离子的制备原料包括钙盐。
作为本发明的一种优选技术方案,所述有机组分的制备原料包括透明质酸、马来酸酐、含有两个羧基的烯烃与含有两个环氧的化合物。
作为本发明的一种优选技术方案,所述透明质酸、马来酸酐、含有两个羧基的烯烃与含有两个环氧的化合物的摩尔比为1:(20~30):(25~35):(20~30)。
作为本发明的一种优选技术方案,所述含有两个羧基的烯烃选自反丁烯二酸、马来酸、2,4-己二烯二酸、辛-4-烯二酸、戊烯二酸中的任意一种或多种的组合。
作为本发明的一种优选技术方案,所述含有两个环氧的化合物选自1,2,3,4-二环氧环戊烷、1,2,7,8-二环氧辛烷、1,2-5,6-二环氧-环辛烷、1,2,6,7-二环氧庚烷、1,2,3,4-二环氧丁烷中的任意一种或多种的组合。
作为本发明的一种优选技术方案,所述杀菌止血组合还包括3~8份助剂,所述助剂包括聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物。
本发明的第二个方面提供了所述纳米银杀菌止血组合物的应用,所述纳米银杀菌止血组合物应用在创可贴、医用纱布、手术用巾、医用海绵、棉棒与止血膜领域中。
本发明的第三个方面提供了所述纳米银杀菌止血组合物的制备方法,至少包括以下步骤:
(1)按重量份向反应器中加入改性透明质酸与乳酸依沙吖啶,再加入水作为溶剂,加热至55℃~75℃溶解,搅拌均匀,得到A液;
(2)将步骤(1)的A液进行处理,得到物质B;
(3)按重量份向步骤(2)的物质B中添加羧甲基壳聚糖接枝聚丙烯酸钠、助剂,加热至60℃~80℃,搅拌均匀,得到物质C;
(4)将步骤(3)中的物质C冷却,过滤,得到固体D;
(5)将步骤(4)中的物质D做灭菌处理,得到纳米银杀菌止血组合物。
本发明与现有技术相比具有以下优点:
(1)本发明采用了改性透明质酸作为纳米银杀菌止血组合物的主要组分,而改性透明质酸中的有机组分一方面提高了组合物体系的保湿性能;另一方面提高了体系对创面渗透液的吸收能力,促进伤口的愈合。而改性透明质酸中的无机组分提高了纳米银杀菌止血组合物的光谱抗菌能力,加快血液凝固,促进伤面愈合;
(2)本发明采用的乳酸依沙吖啶一方面协同作用提高杀菌止血组合物的杀菌效果;另一方面可以防止创面部位水分的挥发,保持创面的湿润性,从而防止因医用材料的粘连而造成的二次创伤;
(3)本发明采用的羧甲基壳聚糖接枝聚丙烯酸钠一方面提高体系的锁水能力,另一方面提高体系的杀菌、止血的性能;
(4)本发明提供的纳米银杀菌止血组合物适用范围广,且制备方法简单,容易进行,易于进行大规模生产。
具体实施方式
本发明第一个方面提供了一种纳米银杀菌止血组合物,所述纳米银杀菌止血组合物的制备原料按重量份计算,包括以下组分:
改性透明质酸 10~50份;
乳酸依沙吖啶 0.5~5份;
羧甲基壳聚糖接枝聚丙烯酸钠 2~8份;
其中,所述改性透明质酸包括有机组分和无机组分;所述无机组分包括纳米银和/钙离子。
优选地,所述纳米银杀菌止血组合物的制备原料按重量份计算,包括以下组分:
改性透明质酸20~40份;
乳酸依沙吖啶2~4份;
羧甲基壳聚糖接枝聚丙烯酸钠4~6份;
其中,所述改性透明质酸包括有机组分和无机组分;所述无机组分包括纳米银和/钙离子。
更优选地,所述纳米银杀菌止血组合物的制备原料按重量份计算,包括以下组分:
改性透明质酸30份;
乳酸依沙吖啶3份;
羧甲基壳聚糖接枝聚丙烯酸钠5份;
其中,所述改性透明质酸包括有机组分和无机组分;所述无机组分包括纳米银和/钙离子。
改性透明质酸:
本发明中,所述改性透明质酸包括有机组分和无机组分;所述有机组分的制备原料包括透明质酸、马来酸酐、含有两个羧基的烯烃与含有两个环氧的化合物;所述无机组分包括纳米银和/或钙离子;所述纳米银的制备原料包括银盐;所述钙离子的制备原料包括钙盐;所述改性透明质酸的制备方法为:
(1)在氮气氛围下,称取透明质酸、马来酸酐、含有两个羧基的烯烃与含有两个环氧的化合物置于反应瓶中,加入N,N-二甲基甲酰胺、四丁基溴化铵,置于90℃的油浴中加热18h;得到物质A;
(2)用无水乙醚对步骤(1)中的物质A洗涤三次,并抽真空,干燥,得到物质B;
(3)取步骤(2)中的物质B溶于N,N-二甲基甲酰胺中,并逐滴加入银盐,在室温下搅拌8h,形成物质C;
(4)向步骤(3)中的C物质中逐滴加入硼氢化钠溶液,搅拌1h后,超声2min,得到物质D;
(5)向步骤(4)的物质D中逐滴加入钙盐,在室温下搅拌8h,形成物质E;
(6)用无水乙醚对步骤(5)的物质E洗涤三次,并抽真空干燥,即得到改性透明质酸。
所述银盐与钙盐重量比是1:(2~5);优选地,所述银盐与钙盐重量比是1:4;所述银盐与钙盐分别是硝酸银与氯化钙。
所述透明质酸、马来酸酐、含有两个羧基的烯烃与含有两个环氧的化合物的摩尔比为1:(20~30):(25~35):(20~30);优选地,所述透明质酸、马来酸酐、含有两个羧基的烯烃与含有两个环氧的化合物的摩尔比为1:(23~27):(27~32):(22~28);更优选地,所述透明质酸、马来酸酐、含有两个羧基的烯烃与含有两个环氧的化合物的摩尔比为1:25:30:26。
所述含有两个羧基的烯烃选自反丁烯二酸、马来酸、2,4-己二烯二酸、辛-4-烯二酸、戊烯二酸中的任意一种或多种的组合;所述反丁烯二酸CAS:110-17-8、马来酸CAS:6915-18-0、2,4-己二烯二酸CAS:1119-72-8、辛-4-烯二酸CAS:14277-16-8、戊烯二酸CAS:1724-02-3;优选地,所述含有两个羧基的烯烃为2,4-己二烯二酸。
所述含有两个环氧的化合物选自1,2,3,4-二环氧环戊烷、1,2,7,8-二环氧辛烷、1,2-5,6-二环氧-环辛烷、1,2,6,7-二环氧庚烷、1,2,3,4-二环氧丁烷中的任意一种或多种的组合;所述1,2:3,4-二环氧环戊烷CAS:187-29-1、1,2,7,8-二环氧辛烷CAS:2426-07-5、1,2-5,6-二环氧-环辛烷CAS:286-75-9、1,2,6,7-二环氧庚烷CAS:4247-19-2、1,2,3,4-二环氧丁烷CAS:564-00-1;优选地,所述含有两个环氧的化合物为1,2,3,4-二环氧丁烷。
优选地,所述改性透明质酸的制备方法为:
(1)在氮气氛围下,称取0.01mol透明质酸、0.25mol马来酸酐、0.3mol2,4-己二烯二酸与0.26mol1,2,3,4-二环氧丁烷置于反应瓶中,加入4.5mL N,N-二甲基甲酰胺、0.001mol四丁基溴化铵,置于90℃的油浴中加热18h;得到物质A;
(2)用20mL无水乙醚对步骤(1)中的物质A洗涤三次,并抽真空,干燥,得到物质B;
(3)取步骤(2)中的物质B溶于3mLN,N-二甲基甲酰胺,用硝酸银和蒸馏水配置形成硝酸银溶液(2mg/mL),并逐滴加入6mL于上述溶液中,在室温下搅拌8h,形成物质C;
(4)向步骤(3)中的C物质中逐滴加入6mL硼氢化钠溶液(20mg/mL),搅拌1h后,超声2min,得到物质D;
(5)用氯化钙和蒸馏水配置形成氯化钙溶液(2mg/mL),并逐滴加入24mL于步骤(4)的物质D中,在室温下搅拌8h,形成物质E;
(6)用50mL无水乙醚对步骤(5)的物质E洗涤三次,并抽真空干燥,即得到改性透明质酸。
乳酸依沙吖啶:
所述乳酸依沙吖啶为黄色结晶性粉末;无臭,味苦。本品在热水中易溶,在沸无水乙醇中溶解,在水中略溶,在乙醇中微溶,在乙醚中不溶;所述乳酸依沙吖啶CAS:1837-57-6。
所述乳酸依沙吖啶适用于敏感革兰阳性菌及革兰阴性菌引起的浅表皮肤感染,如创伤性创口感染、化脓性皮肤感染等;此外,所述乳酸依沙吖啶含有苯环,可用于杀菌止血组合物体系中已形成疏水性的界面,从而能防止创面部位水分的挥发,保持创面的湿润性,从而防止因医用材料的粘连而造成的二次创伤。
羧甲基壳聚糖接枝聚丙烯酸钠:
本发明中,所述羧甲基壳聚糖接枝聚丙烯酸钠为一种分子筛类分子,可吸收大量的水分,从而加快止血速度,并且不会引起创口处因放热而造成的损伤。
在一种实施方式中,所述羧甲基壳聚糖接枝聚丙烯酸钠的制备方法为:
(1)将4.1g羧甲基壳聚糖置于120mL蒸馏水中,在氮气保护下,70℃搅拌30分钟;
(2)加入1.0g偶氮二异丁腈,再搅拌30分钟,降温至50℃;
(3)加入丙烯酸钠水溶液80mL(内含33.0g丙烯酸钠),在70℃下继续搅拌5小时,然后冷却到室温;
(4)加入乙醇200mL作沉淀剂,在室温下搅拌过夜,过滤,所得固体为羧甲基壳聚糖接枝聚丙烯酸钠粗制品;
(5)将所得固体分别用200mL乙醇充分搅拌洗涤三次,再在200mL 80%乙醇溶液中浸泡24小时,然后过滤,真空干燥后粉碎,得羧甲基壳聚糖接枝聚丙烯酸钠粉末。
所述羧甲基壳聚糖CAS:83512-85-0。
在一种实施方式中,所述杀菌止血组合还包括3~8份助剂。
在一种实施方式中,所述助剂包括聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物;所述聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物的重量比为1:(0.5~3):(0.5~3):(0.5~3):(0.5~3);优选地,所述聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物的重量比为1:0.5:0.5:1.5:1。
所述聚维酮碘的CAS:25655-41-8、醋酸氯己定的CAS:206986-79-0、葡萄糖酸氯己定的CAS:18472-51-0、所述蜂胶CAS:9009-62-5;所述田七提取物为市面购得。
本发第二个方面提供了所述纳米银杀菌止血组合物的应用领域,所述纳米银杀菌止血组合物应用于创可贴、医用纱布、手术用巾、医用海绵、棉棒与止血膜领域中。
本发明中第三个方面提供了所述纳米银杀菌止血组合物的制备方法,包括以下步骤:
(1)按重量份向反应器中加入改性透明质酸与乳酸依沙吖啶,再加入水作为溶剂,加热至55℃~75℃溶解,搅拌均匀,得到A液;
(2)将步骤(1)的A液进行处理,得到物质B;
(3)按重量份向步骤(2)的物质B中添加羧甲基壳聚糖接枝聚丙烯酸钠、助剂,加热至60℃~80℃,搅拌均匀,得到物质C;
(4)将步骤(3)中的物质C冷却,过滤,得到固体D;
(5)将步骤(4)中的物质D做灭菌处理,得到纳米银杀菌止血组合物。
在一种实施方式中,步骤(2)中所述后处理的具体步骤是:向步骤(1)的A液中加入0.5mL N-羟基琥珀酰亚胺(0.06mol/L)、1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(0.6mol/L),在45℃下充分搅拌,反应8h。
优选地,所述纳米银杀菌止血组合物的制备方法,包括以下步骤:
(1)按重量份向反应器中加入改性透明质酸与乳酸依沙吖啶,再加入水作为溶剂,加热至55℃~75℃溶解,搅拌均匀,得到A液;
(2)向步骤(1)的A液中加入1mL N-羟基琥珀酰亚胺(0.06mol/L)、1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(0.6mol/L),在45℃下充分搅拌,反应8h,得到物质B;
(3)按重量份向步骤(2)的物质B中添加羧甲基壳聚糖接枝聚丙烯酸钠、助剂,加热至60℃~80℃,搅拌均匀,得到物质C;
(4)将步骤(3)中的物质C冷却,过滤,得到固体D;
(5)将步骤(4)中的物质D做灭菌处理,得到纳米银杀菌止血组合物。
本发明采用了改性透明质酸作为杀菌止血组合物的主要组分,形成以透明质酸为核心,并与聚酯连接形成网络结构,分子链间既有化学作用形成的共价键,又含有物理作用形成的大量氢键,此外,还有大量裸露的亲水性官能团,这样的分子结构一方面提高了组合物体系的保湿性能;另一方面提高了体系对创面渗透液的吸收能力,促进伤口的愈合。而改性透明质酸中的无机组分纳米银以及钙离子提高了杀菌止血组合物的光谱抗菌能力,加快血液凝固,促进伤面愈合。
本发明采用了乳酸依沙吖啶,一方面与体系中的纳米银、钙离子以及聚维酮碘、醋酸氯己定、葡萄糖酸氯己定协同作用提高杀菌止血组合物的杀菌效果;另一方面可以防止创面部位水分的挥发,保持创面的湿润性,从而防止因医用材料的粘连而造成的二次创伤。
本发明采用的羧甲基壳聚糖接枝聚丙烯酸钠含有大量的亲水性基团,与体系中的改性透明质酸之间形成大量的氢键,提高体系的锁水、保湿能力,另一方面也提高体系的杀菌、止血的性能。
实施例1
本发明的实施例1提供了一种纳米银杀菌止血组合物,所述纳米银杀菌止血组合物的制备原料按重量份计算,包括以下组分:
改性透明质酸 30份;
乳酸依沙吖啶 3份;
羧甲基壳聚糖接枝聚丙烯酸钠 5份;
其中,所述改性透明质酸包括有机组分和无机组分;所述无机组分包括纳米银和/或钙离子;
所述改性透明质酸的制备方法为:
(1)在氮气氛围下,称取0.01mol透明质酸、0.25mol马来酸酐、0.3mol2,4-己二烯二酸与0.26mol1,2,3,4-二环氧丁烷置于反应瓶中,加入4.5mL N,N-二甲基甲酰胺、0.001mol四丁基溴化铵,置于90℃的油浴中加热18h;得到物质A;
(2)用20mL无水乙醚对步骤(1)中的物质A洗涤三次,并抽真空,干燥,得到物质B;
(3)取步骤(2)中的物质B溶于3mL N,N-二甲基甲酰胺,用硝酸银和蒸馏水配置形成硝酸银溶液(2mg/mL),并逐滴加入6mL于上述溶液中,在室温下搅拌8h,形成物质C;
(4)向步骤(3)中的C物质中逐滴加入6mL硼氢化钠溶液(20mg/mL),搅拌1h后,超声2min,得到物质D;
(5)用氯化钙和蒸馏水配置形成氯化钙溶液(2mg/mL),并逐滴加入24mL于步骤(4)的物质D中,在室温下搅拌8h,形成物质E;
(6)用50mL无水乙醚对步骤(5)的物质E洗涤三次,并抽真空干燥,即得到改性透明质酸;
所述2,4-己二烯二酸CAS:1119-72-8,所述1,2,3,4-二环氧丁烷CAS:564-00-1;
所述乳酸依沙吖啶CAS:1837-57-6;
所述羧甲基壳聚糖接枝聚丙烯酸钠的制备方法为:
(1)将4.1g羧甲基壳聚糖置于120mL蒸馏水中,在氮气保护下,70℃搅拌30分钟;
(2)加入1.0g偶氮二异丁腈,再搅拌30分钟,降温至50℃;
(3)加入丙烯酸钠水溶液80mL(内含33.0g丙烯酸钠),在70℃下继续搅拌5小时,然后冷却到室温;
(4)加入乙醇200mL作沉淀剂,在室温下搅拌过夜,过滤,所得固体为羧甲基壳聚糖接枝聚丙烯酸钠粗制品;
(5)将所得固体分别用200mL乙醇充分搅拌洗涤三次,再在200mL 80%乙醇溶液中浸泡24小时,然后过滤,真空干燥后粉碎,得羧甲基壳聚糖接枝聚丙烯酸钠粉末。
所述羧甲基壳聚糖CAS:83512-85-0;
所述杀菌止血组合还包括3~8份助剂,所述助剂包括聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物;所述聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物的重量比为1:0.5:0.5:1.5:1;
所述聚维酮碘的CAS:25655-41-8、醋酸氯己定的CAS:206986-79-0、葡萄糖酸氯己定的CAS:18472-51-0、所述蜂胶CAS:9009-62-5;所述田七提取物为市面购得;
所述纳米银杀菌止血组合物的制备方法,包括以下步骤:
(1)按重量份向反应器中加入改性透明质酸与乳酸依沙吖啶,再加入水作为溶剂,加热至55℃~75℃溶解,搅拌均匀,得到A液;
(2)向步骤(1)的A液中加入1mL N-羟基琥珀酰亚胺(0.06mol/L)、1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(0.6mol/L),在45℃下充分搅拌,反应8h,得到物质B;
(3)按权利要求1中的重量份向步骤(2)的物质B中添加羧甲基壳聚糖接枝聚丙烯酸钠、助剂,加热至60℃~80℃,搅拌均匀,得到物质C;
(4)将步骤(3)中的物质C冷却,过滤,得到固体D;
(5)将步骤(4)中的物质D做灭菌处理,得到纳米银杀菌止血组合物。
实施例2
本发明的实施例2提供了一种纳米银杀菌止血组合物,所述纳米银杀菌止血组合物的制备原料按重量份计算,包括以下组分:
改性透明质酸 50份;
乳酸依沙吖啶 5份;
羧甲基壳聚糖接枝聚丙烯酸钠 8份;
其中,所述改性透明质酸包括有机组分和无机组分;所述无机组分包括纳米银和/或钙离子;
所述改性透明质酸的制备方法同实施例1;
所述乳酸依沙吖啶CAS:1837-57-6;
所述羧甲基壳聚糖接枝聚丙烯酸钠的制备方法同实施例1;
所述杀菌止血组合还包括3~8份助剂,所述助剂包括聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物;所述聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物的重量比为1:0.5:0.5:1.5:1;
所述聚维酮碘的CAS:25655-41-8、醋酸氯己定的CAS:206986-79-0、葡萄糖酸氯己定的CAS:18472-51-0、所述蜂胶CAS:9009-62-5;所述田七提取物为市面购得;
所述纳米银杀菌止血组合物的制备方法同实施例1。
实施例3
本发明的实施例3提供了一种纳米银杀菌止血组合物,所述纳米银杀菌止血组合物的制备原料按重量份计算,包括以下组分:
改性透明质酸 10份;
乳酸依沙吖啶 0.5份;
羧甲基壳聚糖接枝聚丙烯酸钠 2份;
其中,所述改性透明质酸包括有机组分和无机组分;所述无机组分包括纳米银和/或钙离子;
所述改性透明质酸的制备方法同实施例1;
所述乳酸依沙吖啶CAS:1837-57-6;
所述羧甲基壳聚糖接枝聚丙烯酸钠的制备方法同实施例1;
所述杀菌止血组合还包括3~8份助剂,所述助剂包括聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物;所述聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物的重量比为1:0.5:0.5:1.5:1;
所述聚维酮碘的CAS:25655-41-8、醋酸氯己定的CAS:206986-79-0、葡萄糖酸氯己定的CAS:18472-51-0、所述蜂胶CAS:9009-62-5;所述田七提取物为市面购得;
所述纳米银杀菌止血组合物的制备方法同实施例1。
实施例4
本发明的实施例4提供了一种纳米银杀菌止血组合物,所述纳米银杀菌止血组合物的制备原料按重量份计算,包括以下组分:
改性透明质酸 30份;
乳酸依沙吖啶 3份;
羧甲基壳聚糖接枝聚丙烯酸钠 5份;
其中,所述改性透明质酸包括有机组分和无机组分;所述无机组分包括纳米银和/或钙离子;
所述改性透明质酸的制备方法为:
(1)在氮气氛围下,称取0.01mol透明质酸、0.2mol马来酸酐、0.25mol2,4-己二烯二酸与0.2mol1,2,3,4-二环氧丁烷置于反应瓶中,加入4.5mL N,N-二甲基甲酰胺、0.001mol四丁基溴化铵,置于90℃的油浴中加热18h;得到物质A;
(2)用20mL无水乙醚对步骤(1)中的物质A洗涤三次,并抽真空,干燥,得到物质B;
(3)取步骤(2)中的物质B溶于3mL N,N-二甲基甲酰胺,用硝酸银和蒸馏水配置形成硝酸银溶液(2mg/mL),并逐滴加入6mL于上述溶液中,在室温下搅拌8h,形成物质C;
(4)向步骤(3)中的C物质中逐滴加入6mL硼氢化钠溶液(20mg/mL),搅拌1h后,超声2min,得到物质D;
(5)用氯化钙和蒸馏水配置形成氯化钙溶液(2mg/mL),并逐滴加入24mL于步骤(4)的物质D中,在室温下搅拌8h,形成物质E;
(6)用50mL无水乙醚对步骤(5)的物质E洗涤三次,并抽真空干燥,即得到改性透明质酸;
所述2,4-己二烯二酸CAS:1119-72-8,所述1,2,3,4-二环氧丁烷CAS:564-00-1;
所述乳酸依沙吖啶CAS:1837-57-6;
所述羧甲基壳聚糖接枝聚丙烯酸钠的制备方法同实施例1;
所述杀菌止血组合还包括3~8份助剂,所述助剂包括聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物;所述聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物的重量比为1:0.5:0.5:1.5:1;
所述聚维酮碘的CAS:25655-41-8、醋酸氯己定的CAS:206986-79-0、葡萄糖酸氯己定的CAS:18472-51-0、所述蜂胶CAS:9009-62-5;所述田七提取物为市面购得;
所述纳米银杀菌止血组合物的制备方法同实施例1。
实施例5
本发明的实施例5提供了一种纳米银杀菌止血组合物,所述纳米银杀菌止血组合物的制备原料按重量份计算,包括以下组分:
改性透明质酸 30份;
乳酸依沙吖啶 3份;
羧甲基壳聚糖接枝聚丙烯酸钠 5份;
其中,所述改性透明质酸包括有机组分和无机组分;所述无机组分包括纳米银和/或钙离子;
所述改性透明质酸的制备方法为:
(1)在氮气氛围下,称取0.01mol透明质酸、0.3mol马来酸酐、0.35mol2,4-己二烯二酸与0.3mol1,2,3,4-二环氧丁烷置于反应瓶中,加入4.5mL N,N-二甲基甲酰胺、0.001mol四丁基溴化铵,置于90℃的油浴中加热18h;得到物质A;
(2)用20mL无水乙醚对步骤(1)中的物质A洗涤三次,并抽真空,干燥,得到物质B;
(3)取步骤(2)中的物质B溶于3mL N,N-二甲基甲酰胺,用硝酸银和蒸馏水配置形成硝酸银溶液(2mg/mL),并逐滴加入6mL于上述溶液中,在室温下搅拌8h,形成物质C;
(4)向步骤(3)中的C物质中逐滴加入6mL硼氢化钠溶液(20mg/mL),搅拌1h后,超声2min,得到物质D;
(5)用氯化钙和蒸馏水配置形成氯化钙溶液(2mg/mL),并逐滴加入24mL于步骤(4)的物质D中,在室温下搅拌8h,形成物质E;
(6)用50mL无水乙醚对步骤(5)的物质E洗涤三次,并抽真空干燥,即得到改性透明质酸;
所述2,4-己二烯二酸CAS:1119-72-8,所述1,2,3,4-二环氧丁烷CAS:564-00-1;
所述乳酸依沙吖啶CAS:1837-57-6;
所述羧甲基壳聚糖接枝聚丙烯酸钠的制备方法同实施例1;
所述杀菌止血组合还包括3~8份助剂,所述助剂包括聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物;所述聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物的重量比为1:0.5:0.5:1.5:1;
所述聚维酮碘的CAS:25655-41-8、醋酸氯己定的CAS:206986-79-0、葡萄糖酸氯己定的CAS:18472-51-0、所述蜂胶CAS:9009-62-5;所述田七提取物为市面购得;
所述纳米银杀菌止血组合物的制备方法同实施例1。
实施例6
本发明提供的实施例6的具体实施方式同实施例1,不同之处,将所述2,4-己二烯二酸替换为辛-4-烯二酸,CAS:14277-16-8。
实施例7
本发明提供的实施例7的具体实施方式同实施例1,不同之处,将所述1,2,3,4-二环氧丁烷替换为1,2,6,7-二环氧庚烷,CAS:4247-19-2。
实施例8
本发明的实施例1提供了一种纳米银杀菌止血组合物,所述纳米银杀菌止血组合物的制备原料按重量份计算,包括以下组分:
改性透明质酸 30份;
乳酸依沙吖啶 3份;
羧甲基壳聚糖接枝聚丙烯酸钠 5份;
其中,所述改性透明质酸包括有机组分和无机组分;所述无机组分包括纳米银和/或钙离子;
所述改性透明质酸的制备方法为:
(1)在氮气氛围下,称取0.01mol透明质酸、0.25mol马来酸酐、0.3mol2,4-己二烯二酸与0.26mol1,2,3,4-二环氧丁烷置于反应瓶中,加入4.5mL N,N-二甲基甲酰胺、0.001mol四丁基溴化铵,置于90℃的油浴中加热18h;得到物质A;
(2)用20mL无水乙醚对步骤(1)中的物质A洗涤三次,并抽真空,干燥,得到物质B;
(3)取步骤(2)中的物质B溶于3mL N,N-二甲基甲酰胺,用硝酸银和蒸馏水配置形成硝酸银溶液(2mg/mL),并逐滴加入6mL于上述溶液中,在室温下搅拌8h,形成物质C;
(4)向步骤(3)中的C物质中逐滴加入6mL硼氢化钠溶液(20mg/mL),搅拌1h后,超声2min,得到物质D;
(5)用氯化钙和蒸馏水配置形成氯化钙溶液(2mg/mL),并逐滴加入30mL于步骤(4)的物质D中,在室温下搅拌8h,形成物质E;
(6)用50mL无水乙醚对步骤(5)的物质E洗涤三次,并抽真空干燥,即得到改性透明质酸;
所述2,4-己二烯二酸CAS:1119-72-8,所述1,2,3,4-二环氧丁烷CAS:564-00-1;
所述乳酸依沙吖啶CAS:1837-57-6;
所述羧甲基壳聚糖接枝聚丙烯酸钠的制备方法同实施例1;
所述杀菌止血组合还包括3~8份助剂,所述助剂包括聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物;所述聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物的重量比为1:0.5:0.5:1.5:1;
所述聚维酮碘的CAS:25655-41-8、醋酸氯己定的CAS:206986-79-0、葡萄糖酸氯己定的CAS:18472-51-0、所述蜂胶CAS:9009-62-5;所述田七提取物为市面购得;
所述纳米银杀菌止血组合物的制备方法同实施例1。
对比例1
对比例1的具体实施方式同实施例1,不同之处,将所述改性透明质酸的重量份替换为0。
对比例2
对比例2的具体实施方式同实施例1,不同之处,将所述改性透明质酸替换为透明质酸。
对比例3
对比例3提供了一种纳米银杀菌止血组合物,所述纳米银杀菌止血组合物的制备原料按重量份计算,包括以下组分:
改性透明质酸 30份;
乳酸依沙吖啶 3份;
羧甲基壳聚糖接枝聚丙烯酸钠 5份;
其中,所述改性透明质酸包括有机组分和无机组分;所述无机组分包括纳米银和/或钙离子;
所述改性透明质酸的制备方法为:
(1)在氮气氛围下,称取0.01mol透明质酸、0.25mol马来酸酐、0.3mol2,4-己二烯二酸与0.26mol1,2,3,4-二环氧丁烷置于反应瓶中,加入4.5mL N,N-二甲基甲酰胺、0.001mol四丁基溴化铵,置于90℃的油浴中加热18h;得到物质A;
(2)用20mL无水乙醚对步骤(1)中的物质A洗涤三次,并抽真空,干燥,得到物质B;物质B即为最后所需物质;
所述2,4-己二烯二酸CAS:1119-72-8,所述1,2,3,4-二环氧丁烷CAS:564-00-1;
所述乳酸依沙吖啶CAS:1837-57-6;
所述羧甲基壳聚糖接枝聚丙烯酸钠的制备方法同实施例1;
所述杀菌止血组合还包括3~8份助剂,所述助剂包括聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物;所述聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物的重量比为1:0.5:0.5:1.5:1;
所述聚维酮碘的CAS:25655-41-8、醋酸氯己定的CAS:206986-79-0、葡萄糖酸氯己定的CAS:18472-51-0、所述蜂胶CAS:9009-62-5;所述田七提取物为市面购得;
所述纳米银杀菌止血组合物的制备方法同实施例1。
对比例4
对比例4的具体实施方式同实施例1,不同之处,将所述乳酸依沙吖啶的重量份替换为0。
对比例5
对比例5的具体实施方式同实施例1,不同之处,将所述羧甲基壳聚糖接枝聚丙烯酸钠的重量份替换为0。
性能评估:
1、抗菌性能
采用S.aureusATCC6538进行杀菌实验。S.aureusATCC6538在LB琼脂上37℃培养24h,制备好的菌悬液浓度为5×107cfu/mL;C.albicansATCC0231在YPD琼脂平板上37℃培养24h,制备好的菌悬液浓度为5×107cfu/mL。将实施例1-8和对比例1-5所得液体分别加入到菌体培养液中,37℃培24h后,取10μL培养液,用平板计数法观察活菌浓度。以PBS作为对照组,从而确定最小杀菌浓度(MBC),结果见表1。
2、保湿性能
将含有一定水分的样品放在35℃的干燥器中干燥,定时称量样品重量份的减少,称出样品的保水量,通过对比分析,比较出不同样品保湿性的大小。向10g实施例1-8及对比例1-5制得的杀菌组合物中加入2g的蒸馏水,然后置入以硅胶为干燥剂的同一干燥器环境中,放置5h,称出样品水分减少量。计算出它们的保水量:保水量=残存水分重量份/样品重量份,结果见表1。
3、创面愈合性能
清洁级SD大鼠,雌雄兼半,体质量240±10g,购于四川大学华西医院动物实验中心,采用乌拉坦(4.5ml·kg-1)腹腔注射将大鼠麻醉,鼠背朝上四肢固定,除去背部毛发,用生理盐水擦拭,在大鼠脊柱两侧距肩胛骨以下4cm处标记一个直径为1.8cm的圆,用镊子将皮肤提起,沿标记线剪去皮肤。分别将实施例1-8及对比例1-5的止血材料涂抹于创面位置,观察21天时创面的愈合情况,其中“创面愈合率”大于等于90%为“完全愈合”;“创面愈合率”小于90%大于等于60%为“愈合”;小于60%为“没有愈合”,具体结果见表1。
4、止血实验
实验动物为雄性大耳白兔13只,体重2.5-3公斤,雌雄兼半,将白兔麻醉,固定在手术台上,手术暴露股静脉并横向切断,令其自由喷血8秒钟后,分别用1g的实施例1-8及对比例1-5的止血材料对创口进行止血,每组分别观察止血时间结果见表1。
表1性能测试结果
最小杀菌浓度(%) | 保湿性能(%) | 创面愈合情况 | 止血时间(s) | |
实施例1 | 0.04 | 93 | 完全愈合 | 20 |
实施例2 | 0.16 | 83 | 愈合 | 31 |
实施例3 | 0.18 | 79 | 愈合 | 35 |
实施例4 | 0.12 | 87 | 愈合 | 24 |
实施例5 | 0.09 | 86 | 愈合 | 29 |
实施例6 | 0.08 | 90 | 愈合 | 22 |
实施例7 | 0.11 | 76 | 愈合 | 26 |
实施例8 | 0.07 | 88 | 愈合 | 23 |
对比例1 | 0.51 | 51 | 没有愈合 | 90 |
对比例2 | 0.41 | 65 | 没有愈合 | 68 |
对比例3 | 0.48 | 55 | 没有愈合 | 85 |
对比例4 | 0.39 | 62 | 没有愈合 | 72 |
对比例5 | 0.31 | 59 | 没有愈合 | 79 |
从上述测试结果可以看出,本发明提供的纳米银杀菌止血组合物中含有的改性透明质酸、乳酸依沙吖啶、羧甲基壳聚糖接枝聚丙烯酸钠体系有良好的保湿性能,提高了纳米银杀菌止血组合物的光谱抗菌能力,加快血液凝固,促进伤面愈合,还可以防止因医用材料的粘连而造成的二次创伤。
以上内容仅仅是对本发明结构所作的举例和说明,并非用来限定本发明的保护范围。所属本技术领域的技术人员在上述技术方案的基础上所作的修改或补充或采用类似的方式替换,只要不偏离发明的结构或者超越本权利要求书所定义的范围,均应属于本发明的保护范围。
Claims (6)
1.一种纳米银杀菌止血组合物,其特征在于,所述纳米银杀菌止血组合物的制备原料按重量份计算,至少包括以下组分:改性透明质酸10~50份;乳酸依沙吖啶0.5~5份;羧甲基壳聚糖接枝聚丙烯酸钠2~8份;其中,所述改性透明质酸包括有机组分和无机组分;所述无机组分包括纳米银和/或钙离子;
所述有机组分的制备原料包括透明质酸、马来酸酐、含有两个羧基的烯烃与含有两个环氧的化合物;
所述有机组分中透明质酸、马来酸酐、含有两个羧基的烯烃与含有两个环氧的化合物的摩尔比为1:(20~30):(25~35):(20~30);
所述含有两个羧基的烯烃选自反丁烯二酸、马来酸、2,4-己二烯二酸、辛-4-烯二酸、戊烯二酸中的任意一种或多种的组合;
所述改性透明质酸的制备方法为:
(1)在氮气氛围下,称取透明质酸、马来酸酐、含有两个羧基的烯烃与含有两个环氧的化合物置于反应瓶中,加入N,N-二甲基甲酰胺、四丁基溴化铵,置于90℃的油浴中加热18h;得到物质A;(2)用无水乙醚对步骤(1)中的物质A洗涤三次,并抽真空,干燥,得到物质B;(3)取步骤(2)中的物质B溶于N,N-二甲基甲酰胺中,并逐滴加入银盐,在室温下搅拌8h,形成物质C;(4)向步骤(3)中的C物质中逐滴加入硼氢化钠溶液,搅拌1h后,超声2min,得到物质D;(5)向步骤(4)的物质D中逐滴加入钙盐,在室温下搅拌8h,形成物质E;(6)用无水乙醚对步骤(5)的物质E洗涤三次,并抽真空干燥,即得到改性透明质酸。
2.根据权利要求1所述的纳米银杀菌止血组合物,其特征在于,所述纳米银的制备原料与所述钙离子的制备原料的摩尔比为1:(2~5)。
3.根据权利要求2所述的纳米银杀菌止血组合物,其特征在于,所述纳米银的制备原料包括银盐;所述钙离子的制备原料为包括钙盐。
4.根据权利要求1所述的纳米银杀菌止血组合物,其特征在于,所述含有两个环氧的化合物选自1,2,3,4-二环氧环戊烷、1,2,7,8-二环氧辛烷、1,2,5,6-二环氧-环辛烷、1,2,6,7-二环氧庚烷、1,2,3,4-二环氧丁烷中的任意一种或多种的组合。
5.根据权利要求1所述的纳米银杀菌止血组合物,其特征在于,所述杀菌止血组合还包括3~8份助剂,所述助剂包括聚维酮碘、醋酸氯己定、葡萄糖酸氯己定、蜂胶与田七提取物。
6.根据权利要求1~5任意一项所述纳米银杀菌止血组合物的制备方法,至少包括以下步骤:(1)按重量份向反应器中加入改性透明质酸与乳酸依沙吖啶,再加入水作为溶剂,加热至55℃~75℃溶解,搅拌均匀,得到A液;(2)将步骤(1)的A液进行处理,得到物质B;(3)按重量份向步骤(2)的物质B中添加羧甲基壳聚糖接枝聚丙烯酸钠、助剂,加热至60℃~80℃,搅拌均匀,得到物质C;(4)将步骤(3)中的物质C冷却,过滤,得到固体D;(5)将步骤(4)中的物质D做灭菌处理,得到纳米银杀菌止血组合物。
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