CN116832227A - 一种基体表面黏附静电络合物涂层的制备方法及其应用 - Google Patents
一种基体表面黏附静电络合物涂层的制备方法及其应用 Download PDFInfo
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- CN116832227A CN116832227A CN202310822730.9A CN202310822730A CN116832227A CN 116832227 A CN116832227 A CN 116832227A CN 202310822730 A CN202310822730 A CN 202310822730A CN 116832227 A CN116832227 A CN 116832227A
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Classifications
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Abstract
本发明属于医疗器材表面功能性涂层技术领域,尤其涉及一种基体表面黏附静电络合物涂层的制备方法及其应用,本发明通过沉淀法,首先从可降解的阳(阴)离子聚合物的水溶液中引入阴(阳)离子表面活性剂,由静电作用力形成沉淀络合物,之后对沉淀络合物进行分离,清洗与干燥,使干燥后的沉淀络合物溶解于有机溶剂中,制得静电络合物涂料,将应用于植入性医疗器材的基体浸没在该静电络合物涂料中,之后经加温干燥固化,在基体表面形成静电络合物涂层,能够广泛地应用于各种植入性医疗器材的表面涂层领域,从而实现抑制细菌黏附、荚膜微生物形成及其感染,提升植入性医疗器材的表面亲水性,提升生物相容性等效果。
Description
技术领域
本发明属于医疗器材表面功能性涂层技术领域,尤其涉及一种基体表面黏附静电络合物涂层的制备方法及其应用。
背景技术
近十年来,抗生素的过量使用促生出越来越多的抗药性细菌,因此,抗生素替代产品的研发迫在眉睫。而阳离子聚合物一直是抗生素替代学术研究和实际应用的研究热点。目前,尿路感染是植入性导尿管引发的常见感染之一,其感染的机理即为细菌和尿液中的营养成分黏附在疏水性的硅胶导尿管基体表面,并繁殖形成微生物荚膜。
由于细菌的细胞膜是由带负电的阴离子脂肪构成,其结构可被阳离子抗菌剂由静电作用里破坏,从而导致细菌的裂解和死亡。阳离子抗菌剂的杀菌主要针对于细菌细胞膜固有的生物特性,因此具有广谱的杀菌效果,且细菌极难进化出有效的抗药性。阳离子抗菌剂在抗菌领域有着广泛的前景。阳离子聚合物涂层实现的方法主要为喷涂,浸润,镀膜等。这些工艺获得的聚合体涂层容易被水冲刷掉或者直接剥离,抗菌性能失效快,使其很难在植入性基体表面形成一层长效的抗菌涂层。而在植入身体后,游离出的阳离子聚合物有可能会造成溶血,凝血,引起免疫反应的副作用,降低阳离子涂层的生物相容性。同时现有的表面化学改性技术虽然可以针对不同表面枝接阳离子聚合物,但其需要复杂的化学反应,限制其产业化应用,且无法适用于所有类型的基体。
同时,由于其带有正电荷的特性,可吸引除细菌以外的灰尘,蛋白质等物质,缓慢的黏附或沉积在涂有阳离子聚合物涂层的物体表面,覆盖掉阳离子聚合物的电荷,使其失去抗菌效果。在正电荷被覆盖以后,灰尘,蛋白质等污垢在表面的聚集,也可以进一步为细菌附着和荚膜微生物的形成提供条件和养料,让细菌的繁殖更加容易。此外,荚膜微生物的形成也大幅度增加了杀菌难度,进而引起相应的感染。
发明内容
本发明的目的是针对上述现有技术的不足,提供一种基体表面黏附静电络合物涂层的制备方法及其应用,通过将正负电荷吸附制成的静电络合物涂料涂覆在基体表面,以形成稳定的、生物相容性较好的抗菌性静电络合物涂层。
本发明解决其技术问题所采用的技术方案是:
一方面,本发明提供一种基体表面黏附静电络合物涂层的制备方法,包括如下步骤:
S1:静电络合物的制备:
S1a:将可降解的阳离子聚合物或阴离子聚合物溶解于去离子水中制得阳离子聚合物溶液或阴离子聚合物溶液;
S1b:将阴离子表面活性剂或阳离子表面活性剂溶解于60v/v%的乙醇水溶液中制得阴离子表面活性剂溶液或阳离子表面活性剂溶液;
S1c:将所述阳离子聚合物溶液和阴离子表面活性剂溶液在剧烈搅拌中混合,或将所述阴离子聚合物溶液和阳离子表面活性剂溶液在剧烈搅拌中混合,得到悬浊液;
S1d:对所述悬浊液进行离心沉淀,得到微粒,对所述微粒进行清洗,将洗净后的所述微粒沉淀冷冻并真空干燥;
S2:表面静电络合物涂层的制备:
S2a:将真空干燥后的所述微粒溶解在非苯类和非烷烃类的有机溶剂中,配制得到所述静电络合物涂料;
S2b:在基体表面涂覆所述静电络合物涂料,经加温干燥后,制得表面具有静电络合物涂层的基体。
优选的,所述阳离子聚合物或阴离子聚合物的质量浓度为1%~10%;所述阴离子表面活性剂或阳离子表面活性剂的质量浓度为1%~10%。
优选的,所述静电络合物涂料的浓度为1~100mg/mL。
优选的,所述阳离子聚合物为多肽类阳离子聚合物;所述阴离子表面活性剂为磺酸类表面活性剂和脂肪类表面活性剂中的一种。
优选的,所述多肽类阳离子聚合物为聚赖氨酸和乳酸链球菌素中的一种;所述磺酸类表面活性剂为琥珀酸二(2-乙基己酯)磺酸钠和月桂基磺酸钠中的一种;所述脂肪类表面活性剂为硬脂酸钠和油酸钠中的一种。
优选的,所述阳离子聚合物为多糖类阳离子聚合物,所述多糖类阳离子聚合物为壳聚糖及其衍生物;所述阴离子表面活性剂为磺酸类表面活性剂,所述磺酸类表面活性剂为琥珀酸二(2-乙基己酯)磺酸钠和月桂基磺酸钠中的一种。
优选的,所述阴离子聚合物为多糖类阴离子聚合物,所述多糖类阴离子聚合物为葡聚糖、海藻酸钠、透明质酸钠和肝素钠中的一种;所述阳离子表面活性剂为三烷基(苄基)甲基氯化铵、二烷基乙醇胺酯甲基硫酸甲酯铵和丙烯酸二乙氨基乙酯氯化铵中的一种。
优选的,所述有机溶剂为甲醇、乙醇、异丙醇、丙酮和乙醚中的一种。
优选的,所述步骤S2中的涂覆方法为浸涂法,其中,步骤S2b包括:
将所述基体浸没在静电络合物涂料中,之后将所述基体从静电络合物涂料中提起取出,所述提起取出的速度为1mm/min-100cm/min,之后经加温干燥,制得表面具有静电络合物涂层的基体。
另一方面,本发明还提供一种基体表面黏附静电络合物涂层的应用,采用上述任一项所述的基体表面黏附静电络合物涂层的制备方法在医疗器材表面制备静电络合物涂层。
本发明的有益效果在于:区别于现有技术,本发明的基体表面黏附静电络合物涂层的制备方法,通过沉淀法,首先从可降解的阳(阴)离子聚合物的水溶液中引入阴(阳)离子表面活性剂,由静电作用力形成沉淀络合物,之后对沉淀络合物进行分离,清洗与干燥,使干燥后的沉淀络合物溶解于有机溶剂中,制得静电络合物涂料,将应用于植入性医疗器材的基体浸没在该静电络合物涂料中,之后经加温干燥固化,以在基体表面形成静电络合物涂层,该涂层不易脱落,合成方法步骤简单,反应条件易行,能够广泛地应用于各种植入性医疗器材的表面涂层领域,静电络合物涂层中屏蔽了正电荷,提高其抗污抗蛋白质黏附效果,从而延长其抗微生物荚膜效果,有效实现抑制细菌黏附、荚膜微生物形成及其感染,提升植入性医疗器材的表面亲水性,提升生物相容性等效果。
附图说明
图1是本发明中表面具有静电络合物涂层的基体的杀菌机理演示图;
图2是本发明各实施例中表面具有静电络合物涂层的硅胶导尿管横截面的对比图;
图3是本发明中表面无静电络合物涂层的硅胶导尿管横截面的扫描电镜图;
图4是本发明实施例一中表面具有静电络合物涂层的硅胶导尿管横截面;
图5是本发明实施例一中表面具有静电络合物涂层的硅胶导尿管横截面经过超声处理后涂层的变化图;
图6是本发明各实施例中表面具有静电络合物涂层的硅胶导尿管的接触杀菌性能对比图;
图7是本发明各实施例中表面具有静电络合物涂层的硅胶导尿管在人工尿液中的抗细菌生物膜性能对比图;
图8是本发明中改性前后硅胶导尿管在人工尿液中抑制抗细菌生物膜的扫描电镜对比图。
具体实施方式
为了更清楚地说明本发明实施例的目的、技术方案和优点,下面将结合附图及实施例对本发明作进一步说明,进行清楚、完整的描述,显然,所描述的实施例是本发明的部分实施例,而不是全部实施例。基于本发明的实施例,本领域普通技术人员在没有付出创造性劳动的前提下所获得的所有其他实施例,都属于本发明的保护范围。
本发明实施例中基体表面黏附静电络合物涂层的制备方法,包括步骤S1、S2,以及步骤S1a、S1b、S1c、S1d、S2a、S2b,具体如下:
S1:静电络合物的制备:
S1a:将可降解的阳离子聚合物或阴离子聚合物溶解于去离子水中制得阳离子聚合物溶液或阴离子聚合物溶液;
其中,阳离子聚合物或阴离子聚合物的质量浓度为1%~10%。
其中,阳离子聚合物采用可降解、具有抗菌性的多肽类阳离子聚合物或多糖类阳离子聚合物:多肽类阳离子聚合物为聚赖氨酸和乳酸链球菌素中的一种,聚赖氨酸包括ε-聚赖氨酸;多糖类阳离子聚合物为壳聚糖及其衍生物,例如壳聚糖季铵盐。
其中,阴离子聚合物采用可降解、具有抗菌性的多糖类阴离子聚合物,该多糖类阴离子聚合物为葡聚糖、海藻酸钠、透明质酸钠和肝素钠中的一种。
S1b:将阴离子表面活性剂或阳离子表面活性剂溶解于60v/v%的乙醇水溶液中制得阴离子表面活性剂溶液或阳离子表面活性剂溶液;
其中,阴离子表面活性剂或阳离子表面活性剂的质量浓度为1%~10%。
当阳离子聚合物采用可降解、具有抗菌性的多肽类阳离子聚合物时,本发明实施例中采用的阴离子表面活性剂为磺酸类表面活性剂和脂肪类表面活性剂中的一种;其中,磺酸类表面活性剂为琥珀酸二(2-乙基己酯)磺酸钠和月桂基磺酸钠中的一种;脂肪类表面活性剂为硬脂酸钠和油酸钠中的一种。
当阳离子聚合物采用可降解、具有抗菌性的多糖类阳离子聚合物时,本发明实施例中采用的阴离子表面活性剂为磺酸类表面活性剂;其中,磺酸类表面活性剂为琥珀酸二(2-乙基己酯)磺酸钠和月桂基磺酸钠中的一种。
当阴离子聚合物采用可降解、具有抗菌性的多糖类阴离子聚合物时,本发明实施例中采用的阳离子表面活性剂为三烷基(苄基)甲基氯化铵、二烷基乙醇胺酯甲基硫酸甲酯铵和丙烯酸二乙氨基乙酯氯化铵中的一种。
S1c:将阳离子聚合物溶液和阴离子表面活性剂溶液在剧烈搅拌中混合,或将阴离子聚合物溶液和阳离子表面活性剂溶液在剧烈搅拌中混合,得到悬浊液;
其中,悬浊液中包含有经过络合反应形成的沉淀络合物,沉淀络合物成乳白色微粒状。
S1d:对悬浊液进行离心沉淀,得到微粒,对微粒进行清洗,将洗净后的微粒沉淀冷冻并真空干燥;
在离心沉淀后需用去离子水清洗多次,至少清洗三次,以洗出没有形成沉淀的游离的阳离子聚合物或阴离子聚合物,以及阴离子表面活性剂或阳离子表面活性剂。
其中,离心沉淀过程中离心机的转速为5000-20000rpm。
S2:表面静电络合物涂层的制备:
S2a:将真空干燥后的微粒溶解在非苯类和非烷烃类的有机溶剂中,配制得到静电络合物涂料;
其中,静电络合物涂料的浓度为1~100mg/mL。
其中,有机溶剂为甲醇、乙醇、异丙醇、丙酮和乙醚中的一种;需要说明的是,有机溶剂不可用苯类和烷烃类溶剂。
S2b:在基体表面涂覆静电络合物涂料,经加温干燥后,制得表面具有静电络合物涂层的基体。
其中,步骤S2中采用浸涂的涂覆方法,首先将乳白色微粒溶解在有机溶剂中,然后再将基体浸没在溶解有乳白色微粒的有机溶剂中,具体的,步骤S2b包括:
将基体浸没在静电络合物涂料中,之后将基体从静电络合物涂料中提起取出,提起取出的速度为1mm/min-100cm/min,之后经加温干燥,制得表面具有静电络合物涂层的基体。
其中,基体能够应用于植入性的医疗器材,制备该植入性的医疗器材的材质包括但不限于聚氨酯,硅胶,金属材料等;植入性的医疗器材例如导尿管。
下面以具体实施例对上述方法做进一步的说明和解释:
实施例1:
(1)静电络合物的制备:
将ε-聚赖氨酸以1%的浓度溶解在去离子水中;
将琥珀酸二(2-乙基己酯)磺酸钠以1%的浓度溶解在60v/v%的乙醇溶液中;
将1%ε-聚赖氨酸溶液滴加到1%琥珀酸二(2-乙基己酯)磺酸钠溶液中,并以1000rpm的速度搅拌15分钟,直至溶液变成混浊的悬浊液;
将悬浊液以10000rpm的速度离心,收取微粒沉淀,然后将微粒沉淀重新分散于去离子水中,以清洗没有形成微粒的ε-聚赖氨酸或琥珀酸二(2-乙基己酯)磺酸钠,并继续离心分离,如此重复三次后,得到ε-聚赖氨酸和琥珀酸二(2-乙基己酯)磺酸钠所形成的微粒,然后将收取的微粒沉淀冷冻并真空干燥,得到冻干的粉末。
(2)表面静电络合物涂层的制备:
将上述(1)中制得的静电络合物的粉末溶解在丙酮中得到1w/w%的静电络合物涂料;
将硅胶导尿管浸没在静电络合物涂料中3min后缓慢垂直提出,进而在硅胶导尿管表面形成一层致密的预制涂层,之后将此硅胶导尿管在40℃下固化15分钟,得到致密干燥的静电络合物涂层,该静电络合物涂层具有抗菌性;记作EPL-AOT涂层。
实施例2:
与实施例1步骤(1),步骤(2)中的步骤相同,仅是将ε-聚赖氨酸替换为壳聚糖季铵盐,将涂层记作QCS-AOT涂层。
实施例3:
与实施例1步骤(1),步骤(2)中的步骤相同,仅是将琥珀酸二(2-乙基己酯)磺酸钠替换为月桂基磺酸钠,将涂层记作EPL-SDS涂层。
实施例4:
与实施例1步骤(1),步骤(2)中的步骤相同,仅是将琥珀酸二(2-乙基己酯)磺酸钠替换为硬脂酸钠,将涂层记作EPL-OAS涂层。
(3)静电络合物涂层的表征
所有经过涂覆改性的基体,如聚氨酯/硅胶导尿管等作为测试材料,皆可用扫描电镜直接观测其横截面并测量出涂层的厚度和均一性。
(4)静电络合物涂层杀菌效果的验证
(4.1)细菌的培养:将粪球菌在-80℃的甘油菌中复苏并隔夜培养,之后进行4个小时的二次传代培养;将培养好的细菌离心,用PBS缓冲液清洗3次,最后并重新悬浮于PBS缓冲液中,制得约108CFU/mL浓度的菌液。
(4.2)接触杀菌效果的验证:将5μL的粪球菌菌液均匀涂抹于测试材料表面;其中阴性对照组为未进行任何改性的硅胶导尿管,测试组为具备抗菌涂料改性的硅胶导尿管(实施例1至4);将涂抹菌液后的测试材料在37℃的培养箱中培养3个小时后,把测试材料浸润于灭菌的PBS缓冲液中将细菌从测试材料表面洗脱下,并涂板计数。
(4.3)人工尿液中抗生物膜效果的验证:将5μL的粪球菌液分散于1mL的人工尿液中,将1cm长的硅胶导尿管浸润在人工尿液中并培养并过夜保存;其中阴性对照组为未进行任何改性的硅胶导尿管,测试组为具备长效抗菌涂层的硅胶导尿管(实施例1至4);之后,将测试材料从取出并用PBS缓冲液洗净悬浮状态的细菌;将洗好的测试材料放在1mL的PBS缓冲液中,冰浴超声15分钟并震荡2分钟;用涂板法计数PBS缓冲液中的细菌浓度;拍摄扫描电镜的样品则不需要在冰浴中超声,在用PBS清洗后用酒精脱水并用戊二醛固定,待在空气中干燥24小时以后拍摄。人工尿液的配方请见表一:
表一:人工尿液配方表
组分 | 浓度 |
尿素 | 18.2g/L |
氯化钠 | 7.5g/L |
氯化钾 | 4.5g/L |
磷酸钠 | 4.8g/L |
肌酸酐 | 2g/L |
白蛋白 | 50mg/L |
(4.4)抗菌及抗生物膜效果的计算:抗菌和抗生物膜效果都可以通过对数减少的方法来衡量:
对数减少=log10(对照组上的细菌数/改性材料上的细菌数)。
接触杀菌和抗生物膜形成验证方法可直观的模拟出实际用于中基体表面与细菌的短时间接触以及基体植入与人体内时,表面与含蛋白质的人体体液长期接触的情况;由于细菌在空气中广泛存在,因此在基体从包装取出后到植入体内这段时间内,会短时间暴露于细菌感染的风险中;接触杀菌测试可以模拟出此类短时间接触细菌时,涂层的杀菌效果。
当基体置于体内以后,人体体液内的多糖及蛋白质会缓慢的黏附在基体表面,从而促进生物膜的形成在抗生物膜形成验证中,基体同样被浸泡于富含蛋白质的细菌培养基中,故可以通过这两项体外实验证明该类涂层的瞬时以及长效的抗菌杀菌效果。
结果分析:
实施例1至4的涂层可以通过硅胶导尿管横截面的扫描电镜直接观测,如图2中所示,其厚度均为10-20微米的致密均一涂层;以实施例1为例,如图3、4、5中所示,该涂层在超声处理后依然可以稳定存在于硅胶导尿管表面,其厚度和均一性未受到明显影响,因此,本发明实施例中提供的制备方法可以在基体表面形成一层稳定致密均一的抗菌的静电络合物涂层。
在与粪球菌共同培养3小时后,具有涂层的硅胶导尿管(实施例1至4)都表现出了优异的接触杀菌效果,其短时间接触杀菌效果都超过了99.999%,如图6中所示,该涂层具有优异的杀菌性能。
在人工尿液中培养后,以琥珀酸二(2-乙基己酯)磺酸钠为阴离子表面活性剂的实施例1和2都表现出好于以月桂基磺酸钠和硬脂酸钠为阴离子表面活性剂的实施例3和4,如图7中所示,其中实施例1和2都达到了大于99.99%的抑制效果。以实施例1为例,在扫描电镜下,如图8中所示,无涂层的硅胶导尿管在与粪球菌共同培养24小时后,会形成明显的粪球菌菌落,即微生物荚膜,而实施例1的表面则没有发现黏附的粪球菌。因此如果以硅胶导尿管为应用场景,则应用琥珀酸二(2-乙基己酯)磺酸钠作为阴离子表面活性剂的配方要优于应用月桂基磺酸钠和硬脂酸钠作为阴离子表面活性剂的配方,这是因为,琥珀酸二(2-乙基己酯)磺酸钠在水中的溶解性弱于月桂基磺酸钠,且硬脂酸钠为脂肪酸根表面活性剂。在加入了尿素、氯化钠、氯化钾、磷酸钠等电解质的人工尿液中,应用了琥珀酸二(2-乙基己酯)磺酸钠形成的涂层会比应用了硬脂酸钠和月桂基磺酸钠的涂层更加稳定且长效地释放ε-聚赖氨酸或壳聚糖季铵盐,从而达到更长效的微生物荚膜抑制效果。
本发明实施例中通过正负电荷吸附制成静电络合物涂料,如图1中所示,可在导尿管表面形成稳定的抗菌静电络合物涂层,能够有效防止尿液中营养成分的黏附,并针对性杀灭细菌,有效防止了导尿管引发的尿路感染,提高了防黏附和杀菌性能,并改善了导尿管表面的疏水性。
应当理解的是,对本领域普通技术人员来说,可以根据上述说明加以改进或变换,而所有这些改进和变换都应属于本发明所附权利要求的保护范围。
Claims (10)
1.一种基体表面黏附静电络合物涂层的制备方法,其特征在于,包括如下步骤:
S1:静电络合物的制备:
S1a:将可降解的阳离子聚合物或阴离子聚合物溶解于去离子水中制得阳离子聚合物溶液或阴离子聚合物溶液;
S1b:将阴离子表面活性剂或阳离子表面活性剂溶解于60v/v%的乙醇水溶液中制得阴离子表面活性剂溶液或阳离子表面活性剂溶液;
S1c:将所述阳离子聚合物溶液和阴离子表面活性剂溶液在剧烈搅拌中混合,或将所述阴离子聚合物溶液和阳离子表面活性剂溶液在剧烈搅拌中混合,得到悬浊液;
S1d:对所述悬浊液进行离心沉淀,得到微粒,对所述微粒进行清洗,将洗净后的所述微粒沉淀冷冻并真空干燥;
S2:表面静电络合物涂层的制备:
S2a:将真空干燥后的所述微粒溶解在非苯类和非烷烃类的有机溶剂中,配制得到所述静电络合物涂料;
S2b:在基体表面涂覆所述静电络合物涂料,经加温干燥后,制得表面具有静电络合物涂层的基体。
2.如权利要求1所述的基体表面黏附静电络合物涂层的制备方法,其特征在于,所述阳离子聚合物或阴离子聚合物的质量浓度为1%~10%;所述阴离子表面活性剂或阳离子表面活性剂的质量浓度为1%~10%。
3.如权利要求2所述的基体表面黏附静电络合物涂层的制备方法,其特征在于,所述静电络合物涂料的浓度为1~100mg/mL。
4.如权利要求1所述的基体表面黏附静电络合物涂层的制备方法,其特征在于,所述阳离子聚合物为多肽类阳离子聚合物;所述阴离子表面活性剂为磺酸类表面活性剂和脂肪类表面活性剂中的一种。
5.如权利要求4所述的基体表面黏附静电络合物涂层的制备方法,其特征在于,所述多肽类阳离子聚合物为聚赖氨酸和乳酸链球菌素中的一种;所述磺酸类表面活性剂为琥珀酸二(2-乙基己酯)磺酸钠和月桂基磺酸钠中的一种;所述脂肪类表面活性剂为硬脂酸钠和油酸钠中的一种。
6.如权利要求1所述的基体表面黏附静电络合物涂层的制备方法,其特征在于,所述阳离子聚合物为多糖类阳离子聚合物,所述多糖类阳离子聚合物为壳聚糖及其衍生物;所述阴离子表面活性剂为磺酸类表面活性剂,所述磺酸类表面活性剂为琥珀酸二(2-乙基己酯)磺酸钠和月桂基磺酸钠中的一种。
7.如权利要求1所述的基体表面黏附静电络合物涂层的制备方法,其特征在于,所述阴离子聚合物为多糖类阴离子聚合物,所述多糖类阴离子聚合物为葡聚糖、海藻酸钠、透明质酸钠和肝素钠中的一种;所述阳离子表面活性剂为三烷基(苄基)甲基氯化铵、二烷基乙醇胺酯甲基硫酸甲酯铵和丙烯酸二乙氨基乙酯氯化铵中的一种。
8.如权利要求1-7任一项所述的基体表面黏附静电络合物涂层的制备方法,其特征在于,所述有机溶剂为甲醇、乙醇、异丙醇、丙酮和乙醚中的一种。
9.如权利要求1-7任一项所述的基体表面黏附静电络合物涂层的制备方法,其特征在于,所述步骤S2中的涂覆方法为浸涂法,其中,步骤S2b包括:
将所述基体浸没在静电络合物涂料中,之后将所述基体从静电络合物涂料中提起取出,所述提起取出的速度为1mm/min-100cm/min,之后经加温干燥,制得表面具有静电络合物涂层的基体。
10.一种基体表面黏附静电络合物涂层的应用,其特征在于,采用如权利要求1-9任一项所述的基体表面黏附静电络合物涂层的制备方法在医疗器材表面制备静电络合物涂层。
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