CN106075577A - 基于有机胍盐和聚乙二醇的抗菌涂层 - Google Patents
基于有机胍盐和聚乙二醇的抗菌涂层 Download PDFInfo
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- CN106075577A CN106075577A CN201610581836.4A CN201610581836A CN106075577A CN 106075577 A CN106075577 A CN 106075577A CN 201610581836 A CN201610581836 A CN 201610581836A CN 106075577 A CN106075577 A CN 106075577A
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- Prior art keywords
- hexamethylene
- poly
- polyethylene glycol
- hydrochloride
- glycol mono
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- Paints Or Removers (AREA)
Abstract
本发明公开了基于有机胍盐和聚乙二醇的抗菌涂层,其组份按重量份数包括聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐20‑30份、烯丙基缩水甘油醚10‑15份、聚乙二醇单烯丙基醚10‑15份,4‑甲苯磺酰氯7‑15份,本发明制作工艺简单,制备的涂层具有良好的抗菌和抗细菌粘附性能,从而达到了抗生物被膜的作用,同时具有较低的哺乳动物细胞毒性。
Description
技术领域
本发明涉及抗菌涂层制备技术领域,具体为基于有机胍盐和聚乙二醇的抗菌涂层。
背景技术
随着现代医学的发展,越来越多的生物医学器件应用于人体,而这些生物医学器件的植入后感染对患者健康构成严重威胁,例如骨科植入物、各类支架、尿路/静脉导管等在使用过程中都存在着较高的感染率,这些感染的起源大多是由于这些设备合成表面细菌粘附和增殖。因此,医疗和卫生保健系统迫切需要开发新技术来减少各种植入的生物医学设备引起的感染。近年来,许多研究人员关注在抗菌涂层技术,不少研究都证实了其可以有效地减少微生物感染,特别是这一技术可以避免过量使用传统的抗生素,通过表面修饰方法而不改变材料的本体性能,建立一层表面抗菌涂层于生物医学器件或植入物,以防止微生物粘附以及抑制其扩散,或者在微生物和表面接触时就杀死它们。
发明内容
本发明的目的在于提供基于有机胍盐和聚乙二醇的抗菌涂层,以解决上述背景技术中提出的问题。
为实现上述目的,本发明提供如下技术方案:基于有机胍盐和聚乙二醇的抗菌涂层,其组份按重量份数包括聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐20-30份、烯丙基缩水甘油醚10-15份、聚乙二醇单烯丙基醚10-15份,4-甲苯磺酰氯7-15份。
优选的,其制备方法包括以下步骤:
A、对甲苯磺酰基聚乙二醇单烯丙基醚的合成方法包括以下步骤:
a、将0.056摩尔聚乙二醇单烯丙基醚添加到含有10毫升无水吡啶的三口圆底烧瓶内,在氮气保护下冰浴搅拌;
b、之后将0.102摩尔4-甲苯磺酰氯添加进三口圆底烧瓶内搅拌5小时;之后将60毫升二氯甲烷添加进三口圆底烧瓶内,在室温下搅拌30小时;
c、之后,混合稀释了60毫升二氯甲烷和2100毫升有机相随后用水、100毫升浓度为10mol/L盐酸水溶液,100毫升浓度为1.2mol/L饱和碳酸氢钠洗脱;
d、然后加入硫酸镁进行干燥,最后采用用真空蒸馏,得到一种无色液体。
B、聚乙二醇单烯丙基醚功能化聚六亚甲基胍或聚六亚甲基双胍的制备包括以下步骤:
a、将聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐溶解于甲醇,配成20%质量浓度的溶液;
b、在溶液中加入4摩尔当量的碳酸钾,搅拌均匀;
c、将反应混合物用氮气保护条件下加热到65℃至回流30分钟,将1.2或2.4当量的聚乙二醇单烯丙基醚加入,在65℃下回流反应24小时;
d、反应结束后,混合液用0.5摩尔盐酸溶液中和至中性,然后在透析袋中透析4至5天,浓缩后冷冻干燥得到产品聚六亚甲基胍-聚乙二醇单烯丙基醚二嵌段共聚物,或聚六亚甲基双胍-聚乙二醇单烯丙基醚二嵌段共聚物。
C、烯丙基功能化聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐的制备方法包括以下步骤:
a、将一定量浓度为38.0wt%的聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐低聚物溶液在DMSO中,之后将混合物倒入配有电磁搅拌器的圆底烧瓶内;
b、对圆底烧瓶进行加热,加热温度为60℃-65℃,加热持续时间为30分钟-40分钟,之后迅速注入一定体积的烯丙基缩水甘油醚,且烯丙基缩水甘油醚与聚六亚甲基胍盐酸盐的进料摩尔比为1.0,得到混合物A、;
c、混合物A在60℃下在不断搅拌,反应60小时结束,粗产物通过反复沉淀、溶解在丙酮或甲醇溶液中三次,来完全去除DMSO和未反应的烯丙基缩水甘油醚,得到混合物B;
d、将混合物B在室温下真空干燥后12小时,得到纯化产物。
与现有技术相比,本发明的有益效果是:本发明制作工艺简单,制备的涂层具有良好的抗菌和抗细菌粘附性能,从而达到了抗生物被膜的作用,同时具有较低的哺乳动物细胞毒性;另外,本发明制得的涂层不但表面抗菌而且抗生物膜,改性涂层表面不支持细菌细胞附着,因此预防生物膜的形成。经过烯丙基缩水甘油醚和聚乙二醇单烯丙基醚改性后涂层表面增加了表面亲水性被认为有助于抗生物膜,与其他抗生素涂层技术相比,这种抗生物膜属性使得修饰后的聚六亚甲基胍盐酸盐成为表面涂层一个优越的选择。
附图说明
图1为本发明的聚六亚甲基胍盐酸盐和烯丙基缩水甘油醚以及对甲苯磺酰基聚乙二醇单烯丙基醚的反应示意图。
具体实施方式
下面将结合本发明实施例中的附图,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
请参阅图1,本发明提供一种技术方案:基于有机胍盐和聚乙二醇的抗菌涂层,其组份按重量份数包括聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐20-30份、烯丙基缩水甘油醚10-15份、聚乙二醇单烯丙基醚10-15份,4-甲苯磺酰氯7-15份。
实施例一:
采用的成分配比为:聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐20份、烯丙基缩水甘油醚10份、聚乙二醇单烯丙基醚10份,4-甲苯磺酰氯7份。
本实施例的制备方法包括以下步骤:
其制备方法包括以下步骤:
A、对甲苯磺酰基聚乙二醇单烯丙基醚的合成方法包括以下步骤:
a、将0.056摩尔聚乙二醇单烯丙基醚添加到含有10毫升无水吡啶的三口圆底烧瓶内,在氮气保护下冰浴搅拌;
b、之后将0.102摩尔4-甲苯磺酰氯添加进三口圆底烧瓶内搅拌5小时;之后将60毫升二氯甲烷添加进三口圆底烧瓶内,在室温下搅拌30小时;
c、之后,混合稀释了60毫升二氯甲烷和2100毫升有机相随后用水、100毫升浓度为10mol/L盐酸水溶液,100毫升浓度为1.2mol/L饱和碳酸氢钠洗脱;
d、然后加入硫酸镁进行干燥,最后采用用真空蒸馏,得到一种无色液体。
B、聚乙二醇单烯丙基醚功能化聚六亚甲基胍或聚六亚甲基双胍的制备包括以下步骤:
a、将聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐溶解于甲醇,配成20%质量浓度的溶液;
b、在溶液中加入4摩尔当量的碳酸钾,搅拌均匀;
c、将反应混合物用氮气保护条件下加热到65℃至回流30分钟,将1.2当量的聚乙二醇单烯丙基醚加入,在65℃下回流反应24小时;
d、反应结束后,混合液用0.5摩尔盐酸溶液中和至中性,然后在透析袋中透析4天,浓缩后冷冻干燥得到产品聚六亚甲基胍-聚乙二醇单烯丙基醚二嵌段共聚物,或聚六亚甲基双胍-聚乙二醇单烯丙基醚二嵌段共聚物。
C、烯丙基功能化聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐的制备方法包括以下步骤:
a、将一定量浓度为38.0wt%的聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐低聚物溶液在DMSO中,之后将混合物倒入配有电磁搅拌器的圆底烧瓶内;
b、对圆底烧瓶进行加热,加热温度为60℃,加热持续时间为30分钟,之后迅速注入一定体积的烯丙基缩水甘油醚,且烯丙基缩水甘油醚与聚六亚甲基胍盐酸盐的进料摩尔比为1.0,得到混合物A、;
c、混合物A在60℃下在不断搅拌,反应60小时结束,粗产物通过反复沉淀、溶解在丙酮或甲醇溶液中三次,来完全去除DMSO和未反应的烯丙基缩水甘油醚,得到混合物B;
d、将混合物B在室温下真空干燥后12小时,得到纯化产物。
实施例二:
采用的成分配比为:聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐30份、烯丙基缩水甘油醚15份、聚乙二醇单烯丙基醚15份,4-甲苯磺酰氯15份。
本实施例的制备方法包括以下步骤:
A、对甲苯磺酰基聚乙二醇单烯丙基醚的合成方法包括以下步骤:
a、将0.056摩尔聚乙二醇单烯丙基醚添加到含有10毫升无水吡啶的三口圆底烧瓶内,在氮气保护下冰浴搅拌;
b、之后将0.102摩尔4-甲苯磺酰氯添加进三口圆底烧瓶内搅拌5小时;之后将60毫升二氯甲烷添加进三口圆底烧瓶内,在室温下搅拌30小时;
c、之后,混合稀释了60毫升二氯甲烷和2100毫升有机相随后用水、100毫升浓度为10mol/L盐酸水溶液,100毫升浓度为1.2mol/L饱和碳酸氢钠洗脱;
d、然后加入硫酸镁进行干燥,最后采用用真空蒸馏,得到一种无色液体。
B、聚乙二醇单烯丙基醚功能化聚六亚甲基胍或聚六亚甲基双胍的制备包括以下步骤:
a、将聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐溶解于甲醇,配成20%质量浓度的溶液;
b、在溶液中加入4摩尔当量的碳酸钾,搅拌均匀;
c、将反应混合物用氮气保护条件下加热到65℃至回流30分钟,将2.4当量的聚乙二醇单烯丙基醚加入,在65℃下回流反应24小时;
d、反应结束后,混合液用0.5摩尔盐酸溶液中和至中性,然后在透析袋中透析5天,浓缩后冷冻干燥得到产品聚六亚甲基胍-聚乙二醇单烯丙基醚二嵌段共聚物,或聚六亚甲基双胍-聚乙二醇单烯丙基醚二嵌段共聚物。
C、烯丙基功能化聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐的制备方法包括以下步骤:
a、将一定量浓度为38.0wt%的聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐低聚物溶液在DMSO中,之后将混合物倒入配有电磁搅拌器的圆底烧瓶内;
b、对圆底烧瓶进行加热,加热温度为65℃,加热持续时间为40分钟,之后迅速注入一定体积的烯丙基缩水甘油醚,且烯丙基缩水甘油醚与聚六亚甲基胍盐酸盐的进料摩尔比为1.0,得到混合物A、;
c、混合物A在60℃下在不断搅拌,反应60小时结束,粗产物通过反复沉淀、溶解在丙酮或甲醇溶液中三次,来完全去除DMSO和未反应的烯丙基缩水甘油醚,得到混合物B;
d、将混合物B在室温下真空干燥后12小时,得到纯化产物。
实施例三:
采用的成分配比为:聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐25份、烯丙基缩水甘油醚12份、聚乙二醇单烯丙基醚12份,4-甲苯磺酰氯11份。
本实施例的制备方法包括以下步骤:
A、对甲苯磺酰基聚乙二醇单烯丙基醚的合成方法包括以下步骤:
a、将0.056摩尔聚乙二醇单烯丙基醚添加到含有10毫升无水吡啶的三口圆底烧瓶内,在氮气保护下冰浴搅拌;
b、之后将0.102摩尔4-甲苯磺酰氯添加进三口圆底烧瓶内搅拌5小时;之后将60毫升二氯甲烷添加进三口圆底烧瓶内,在室温下搅拌30小时;
c、之后,混合稀释了60毫升二氯甲烷和2100毫升有机相随后用水、100毫升浓度为10mol/L盐酸水溶液,100毫升浓度为1.2mol/L饱和碳酸氢钠洗脱;
d、然后加入硫酸镁进行干燥,最后采用用真空蒸馏,得到一种无色液体。
B、聚乙二醇单烯丙基醚功能化聚六亚甲基胍或聚六亚甲基双胍的制备包括以下步骤:
a、将聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐溶解于甲醇,配成20%质量浓度的溶液;
b、在溶液中加入4摩尔当量的碳酸钾,搅拌均匀;
c、将反应混合物用氮气保护条件下加热到65℃至回流30分钟,将1.2当量的聚乙二醇单烯丙基醚加入,在65℃下回流反应24小时;
d、反应结束后,混合液用0.5摩尔盐酸溶液中和至中性,然后在透析袋中透析4天,浓缩后冷冻干燥得到产品聚六亚甲基胍-聚乙二醇单烯丙基醚二嵌段共聚物,或聚六亚甲基双胍-聚乙二醇单烯丙基醚二嵌段共聚物。
C、烯丙基功能化聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐的制备方法包括以下步骤:
a、将一定量浓度为38.0wt%的聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐低聚物溶液在DMSO中,之后将混合物倒入配有电磁搅拌器的圆底烧瓶内;
b、对圆底烧瓶进行加热,加热温度为62℃,加热持续时间为35分钟,之后迅速注入一定体积的烯丙基缩水甘油醚,且烯丙基缩水甘油醚与聚六亚甲基胍盐酸盐的进料摩尔比为1.0,得到混合物A、;
c、混合物A在60℃下在不断搅拌,反应60小时结束,粗产物通过反复沉淀、溶解在丙酮或甲醇溶液中三次,来完全去除DMSO和未反应的烯丙基缩水甘油醚,得到混合物B;
d、将混合物B在室温下真空干燥后12小时,得到纯化产物。
本发明制备的涂层进行最小抑菌浓度测定:使用了大肠杆菌、金黄色葡萄球菌、铜绿假单胞菌和腐皮镰孢菌通过使用一个标准的对倍稀释法测定了原始聚六亚甲基胍盐酸盐和修饰过后的聚六亚甲基胍盐酸盐的最小抑菌浓度;首先,96孔板上加入100.0微升不同浓度的原始聚六亚甲基胍盐酸盐,烯丙基缩水甘油醚修饰聚六亚甲基胍盐酸盐、聚乙二醇单烯丙基醚修饰聚六亚甲基胍盐酸盐;接着,100.0微升106CFU/毫升浓度的细菌或真菌孢子悬浮液被添加到孔板内使得最后微生物浓度是5×105CFU/毫升。96孔板放置在37.0℃的微生物培养箱内培养16小时取出。从每个孔吸出5.0μl细胞悬液涂布在穆勒-辛顿琼脂培养基上。最低抑制浓度的结果通过样品浓度的孔内吸出的混合液在琼脂板上没有菌落可以观察到,测定数据如下表:
本发明修饰后的聚六亚甲基胍盐酸盐涂层聚二甲基硅氧烷进行表面抗菌活性测定:首先,金黄色葡萄球菌和铜绿假单胞菌菌株在LB培养基37℃培养16小时,过夜的细菌悬液重新接种于新鲜培养基内生长到OD600=0.5。此外,腐皮镰孢菌是种植在YM琼脂斜面28℃培养72小时后,通过添加2毫升的聚丁二酸丁二醇酯到上述的斜面中,用旋涡震荡器震荡1分钟后得到它的孢子,以上的三个菌液稀释至1×107cfu/毫升的浓度备用;取35毫米无菌培养皿放置材料,10.0μl细菌和真菌的孢子悬浮液分别滴加在每个修饰后的聚六亚甲基胍盐酸盐涂层表面,然后覆盖另一个聚二甲基硅氧烷片,轻轻按压将培养液散布在整个表面,样品放置37.0℃微生物培养箱内培育1小时后取出,2毫升聚丁二酸丁二醇酯添加到35毫米培养皿洗下所有的微生物,再从每个培养皿内取100.0微升的混合液涂布在LB琼脂培养基上计算菌落数。杀死率是由下列公式计算而来的:
杀死率=×100%
实验重复三次,经过上述测试后,用75%的乙醇浸泡30分钟这些涂层片用于清洗,然后再用超纯水清洗这些涂层片数遍,在空气中干燥后,开始第二次测试,方法同上,一直做到第10次的重复。
本发明修饰后的聚六亚甲基胍盐酸盐涂层聚二甲基硅氧烷进行表面抗生物膜性能测定:过夜培养的铜绿假单胞菌用MH肉汤培养基稀释至浓度1×108cfu/毫升。烯丙基缩水甘油醚修饰聚六亚甲基胍盐酸盐涂层片、分子量为1200的聚乙二醇单烯丙基醚修饰聚六亚甲基胍盐酸盐涂层片、分子量为2400的聚乙二醇单烯丙基醚修饰聚六亚甲基胍盐酸盐涂层片和原始的聚二甲基硅氧烷幻灯片都沉浸在2.0毫升细菌悬液内5天,以确保完整的生物膜形成,5天后,每片聚二甲基硅氧烷片上的浮游细菌被聚丁二酸丁二醇酯清洗干净,接着,各种聚二甲基硅氧烷片使用活/死试剂盒染色,染色之后的样品用LSM710倒置荧光显微镜观测。检测SYTO 9,激发波长被设定为488纳米,而PI检测的激发波长561纳米。图像在激发波长处使用Zen 2009软件拍摄以及处理。
本发明制备的涂层进行抗血小板粘附测试:富含血小板血浆通过离心健康兔新鲜血液在1000转/分钟离心15分钟获得。首先,聚二甲基硅氧烷片浸在37℃聚丁二酸丁二醇酯溶液中1小时,之后,聚丁二酸丁二醇酯溶液移走并加入1毫升的富含血小板血浆,聚二甲基硅氧烷片与富含血小板血浆在37℃中培育30分钟后移走富含血小板血浆,然后用聚丁二酸丁二醇酯冲洗至少三次。最后,使用2.5wt%戊二醛4℃固定过夜,再通过不同浓度梯度的乙醇溶液脱水并真空干燥备用,样品用扫描电子显微镜观察。
本发明制备的涂层溶血性试验:取新鲜人类红细胞用Tris缓冲液冲洗三次,每次以900转/分钟的速度离心10分钟,最后用Tris稀释至最终红细胞浓度为5.0%。原始的和修饰后的聚六亚甲基胍盐酸盐涂层聚二甲基硅氧烷都浸泡在37℃的2.0毫升人类红细胞溶液内培育1小时,之后,样本以1000转/分钟的速度离心5分钟取上清液用酶标仪测定其540纳米处的吸光值。0%溶血和100%溶血值分别用只加入Tris和1%的Triton X代表。
本发明制备的涂层进行细胞毒性试验:分子量为2400的聚乙二醇单烯丙基醚修饰聚六亚甲基胍盐酸盐涂层片被切成1平方厘米大小并在121℃高压灭菌20分钟,再放置在24孔板用聚丁二酸丁二醇酯溶液中浸泡16小时。之后,平滑肌细胞和培养基被添加孔板内,细胞种植5天,培养基每2天一换,在第1,3,5天,含有分子量为2400的聚乙二醇单烯丙基醚修饰聚六亚甲基胍盐酸盐涂层片空白原始的聚二甲基硅氧烷片的空版内的细胞使用活/死染色试剂盒染色用倒置荧光显微镜观测,其中,检测FITC,激发波长为488纳米。Rhod检测的激发波长561纳米。图像在激发波长处使用Zen 2009软件拍摄并处理。
本发明中采用的聚六亚甲基胍,已被证实有较高的抗菌活性,被广泛用作消毒剂和杀菌剂在局部伤口和环境。其机理是破坏菌体的细胞膜。
烯丙基缩水甘油醚的活性环氧基的很容易与各种反应官能团如羟基、羧基、氨基通过SN2亲核开环替换反应。活跃的聚六亚甲基胍末端氨基将与环氧基反应,形成carbon-to-carbon双键。此外,实验中用的烯丙基聚乙二醇是新一代的聚(羧酸)高效减水剂的重要原料,因为大多数生物医学设备是由有机硅聚合物材料制作,而其中聚二甲基硅氧烷是使用最广泛的材料之一,因此实验把聚二甲基硅氧烷作为模型,本发明采用氩等离子体技术进行涂层前处理,等离子体表面处理技术也用于许多其他生物材料表面,本发明中应用氩等离子体处理聚二甲基硅氧烷表面;本发明采用了许多不同的测试方法表征各种被修饰后的聚六亚甲基胍涂层的聚二甲基硅氧烷表面,众所周知,生物膜难以根除,传统抗生素对它们的效果收效甚微,细菌生物被膜在生物材料产生胞外多糖矩阵,保护他们免受抗生素和宿主的身体先天免疫系统。因此,至关重要的是,本发明制得的涂层不但表面抗菌而且抗生物膜,改性涂层表面不支持细菌细胞附着,因此预防生物膜的形成。经过烯丙基缩水甘油醚和聚乙二醇单烯丙基醚改性后涂层表面增加了表面亲水性被认为有助于抗生物膜,与其他抗生素涂层技术相比,这种抗生物膜属性使得修饰后的聚六亚甲基胍盐酸盐成为表面涂层一个优越的选择。
为生物医学植入体而言,它们对哺乳细胞毒性是至关重要的一个考量。传统的抗菌材料,如银离子,尽管杀菌性能很强,但是并不广泛用于表面涂层,因为存在较高的细胞毒性。修饰后聚六亚甲基胍盐酸盐涂层的聚二甲基硅氧烷幻灯片经过溶血性试验,发现几乎是无毒的,溶血率低于2.0%,说明抗菌表面有良好的生物相容性。接着让涂层聚二甲基硅氧烷与平滑肌细胞接触时,细胞5天内生长良好,显示良好的细胞生存能力。这个结果表明涂层聚二甲基硅氧烷对细菌细胞和哺乳动物细胞有良好的选择性。
本发明制作工艺简单,制备的涂层具有良好的抗菌和抗细菌粘附性能,从而达到了抗生物被膜的作用,同时具有较低的哺乳动物细胞毒性。
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 (2)
1.基于有机胍盐和聚乙二醇的抗菌涂层,其特征在于:其组份按重量份数包括聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐20-30份、烯丙基缩水甘油醚10-15份、聚乙二醇单烯丙基醚10-15份,4-甲苯磺酰氯7-15份。
2.根据权利要求1所述的基于有机胍盐和聚乙二醇的抗菌涂层,其特征在于:其制备方法包括以下步骤:
A、对甲苯磺酰基聚乙二醇单烯丙基醚的合成方法包括以下步骤:
a、将0.056摩尔聚乙二醇单烯丙基醚添加到含有10毫升无水吡啶的三口圆底烧瓶内,在氮气保护下冰浴搅拌;
b、之后将0.102摩尔4-甲苯磺酰氯添加进三口圆底烧瓶内搅拌5小时;之后将60毫升二氯甲烷添加进三口圆底烧瓶内,在室温下搅拌30小时;
c、之后,混合稀释了60毫升二氯甲烷和2100毫升有机相随后用水、100毫升浓度为10mol/L盐酸水溶液,100毫升浓度为1.2mol/L饱和碳酸氢钠洗脱;
d、然后加入硫酸镁进行干燥,最后采用用真空蒸馏,得到一种无色液体。
B、聚乙二醇单烯丙基醚功能化聚六亚甲基胍或聚六亚甲基双胍的制备包括以下步骤:
a、将聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐溶解于甲醇,配成20%质量浓度的溶液;
b、在溶液中加入4摩尔当量的碳酸钾,搅拌均匀;
c、将反应混合物用氮气保护条件下加热到65℃至回流30分钟,将1.2或2.4当量的聚乙二醇单烯丙基醚加入,在65℃下回流反应24小时;
d、反应结束后,混合液用0.5摩尔盐酸溶液中和至中性,然后在透析袋中透析4至5天,浓缩后冷冻干燥得到产品聚六亚甲基胍-聚乙二醇单烯丙基醚二嵌段共聚物,或聚六亚甲基双胍-聚乙二醇单烯丙基醚二嵌段共聚物。
C、烯丙基功能化聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐的制备方法包括以下步骤:
a、将一定量浓度为38.0wt%的聚六亚甲基胍盐酸盐或聚六亚甲基双胍盐酸盐低聚物溶液在DMSO中,之后将混合物倒入配有电磁搅拌器的圆底烧瓶内;
b、对圆底烧瓶进行加热,加热温度为60℃-65℃,加热持续时间为30分钟-40分钟,之后迅速注入一定体积的烯丙基缩水甘油醚,且烯丙基缩水甘油醚与聚六亚甲基胍盐酸盐的进料摩尔比为1.0,得到混合物A、;
c、混合物A在60℃下在不断搅拌,反应60小时结束,粗产物通过反复沉淀、溶解在丙酮或甲醇溶液中三次,来完全去除DMSO和未反应的烯丙基缩水甘油醚,得到混合物B;
d、将混合物B在室温下真空干燥后12小时,得到纯化产物。
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