CN114853923B - 一种双亲性壳聚糖胶体稳定剂及其制备方法、全水相乳液及其制备方法 - Google Patents
一种双亲性壳聚糖胶体稳定剂及其制备方法、全水相乳液及其制备方法 Download PDFInfo
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Abstract
本发明提供了一种双亲性壳聚糖胶体稳定剂及其制备方法、全水相乳液及其制备方法,利用N‑烷基化反应将疏水基团接枝到壳聚糖侧链制备不同结构的双亲性壳聚糖,再通过疏水相互作用诱导自组装形成双亲性壳聚糖胶体,作为乳化剂稳定全水相乳液。与线性聚合物乳化剂和传统的胶体颗粒乳化剂相比,避免了繁琐的实验合成条件和复杂的制备过程。形成的双亲性壳聚糖胶体的结构及性能可调控性强,可将活性物质负载到水‑水两相界面,实现活性物质的多重负载。制备的多功能全水相乳液在食品、化妆品、生物医学等领域具有潜在的应用前景。
Description
技术领域
本发明属于高分子材料技术领域和乳液领域,具体涉及一种双亲性壳聚糖胶体稳定剂及其制备方法、全水相乳液及其制备方法。
背景技术
乳液是两种互不相溶的液体在机械力或其他外力作用下,其中一种液体以微小液滴的形式分散于另一种液体所形成的热力学不稳定的分散体。添加稳定剂可阻止液滴聚并,使乳液达到稳定状态。传统乳液中互不相溶的两相分别为油相和水相,根据形成乳液的液滴内外相的不同,可分为油包水(W/O)、水包油(O/W)、水包油包水(W/O/W)、油包水包油(O/W/O)等多种类型的乳液。
除了上述常见的油-水乳液外,两种互不相溶的水溶液也可以产生乳液。全水相乳液(也称为水包水乳液、双水相乳液)是利用聚合物与聚合物/无机盐等在水溶液中自发的离散型相分离行为而形成的水-水分散体系。由于全水相乳液成分不含油相,具有无毒、绿色环保和更好的生物相容性等特点,在化妆品、食品、生物技术和药物输送方面的高级应用中避免了更多的有毒成分。
然而,全水相乳液拥有着极低的表面张力(10-1N/m-10-6N/m)和较大的界面厚度(几十到几百纳米),传统的用来稳定油水乳液的表面活性剂很难穿透整个界面,不能用于全水相乳液的稳定。因此,寻找合适的全水相乳液稳定剂是目前研究的热点。
发明内容
本发明的目的在于提供一种双亲性壳聚糖胶体稳定剂及其制备方法,利用N-烷基化反应将疏水基团接枝到壳聚糖侧链制备不同结构的双亲性壳聚糖(AmCS),再通过疏水相互作用诱导自组装形成双亲性壳聚糖胶体(AmCS CPs),作为乳化剂稳定全水相乳液。
本发明还有一个目的在于提供一种全水相乳液及其制备方法,利用上述双亲性壳聚糖胶体稳定剂制备。
本发明具体技术方案如下:
一种双亲性壳聚糖胶体稳定剂的制备方法,包括以下步骤:
1)双亲性壳聚糖的制备:
将壳聚糖、碱和异丙醇混合,匀速搅拌并加热反应使壳聚糖碱化,再继续升温滴加卤代烃,恒温搅拌反应后,制备N-烷基化壳聚糖,反应结束后,离心分离得到固体,纯化、烘干,得到双亲性壳聚糖(AmCS);
2)双亲性壳聚糖胶体的制备:
将双亲性壳聚糖溶于有机溶剂中,在搅拌下逐滴加入超纯水,至出现丁达尔现象,再透析除去有机溶剂,得到双亲性壳聚糖胶体(AmCS CPs)。
步骤1)中所述碱为氢氧化钾或氢氧化钠;
步骤1)中所述卤代烃取代基是烷烃或芳烃;优选的为氯辛烷、氯代正十六烷或苄基氯;
步骤1)中壳聚糖、碱、异丙醇的质量比为是1:1:20;
步骤1)中所述加热反应使壳聚糖碱化是指碱化温度到达40-65℃后恒温反应0.5-4h以使壳聚糖碱化;
步骤1)中继续升温达到60-110℃滴加卤代烃,恒温60-110℃搅拌反应,反应时间为3-5h;
步骤1)中卤代烃与壳聚糖单体的用量摩尔比0.1:1-4.5:1。
步骤1)中所述纯化具体为:离心分离得到固体后,加入适量蒸馏水,用稀盐酸中和至中性,产物在丙酮中充分沉淀后过滤,用体积比为7:3的乙醇和水混合溶液洗涤,直至洗出的水中不再有卤离子,再用无水乙醇洗涤,离心分离。
步骤1)中所述烘干是指80℃下烘干至恒重。
本发明控制适当的碱化时间,可以使壳聚糖内的立体规整性得到充分破坏,壳聚糖与碱接触更充分、碱化更彻底,使烷基化反应更容易发生,但是过长的碱化时间会造成壳聚糖结焦,对烷基化反应不利;适当的碱化温度下,壳聚糖内分子热运动会加剧,分子内及分子间氢键更容易破坏,大量的氨基暴露出来,增加了与卤代烃的接触机会,使烷基化反应更容易发生,而如果碱化温度过高会使壳聚糖焦化、降解程度加剧,烷基化壳聚糖取代度就会降低;反应时间过短或过长也会使取代度变化。反应时间在3-5h之间都可实现。随着反应温度的升高,产品的取代度会随之增大,反应温度太低,会导致原料反应不完全或不发生反应:而反应温度太高会使壳聚糖结焦、降解程度加剧,使得取代度下降。此外,氢氧化钠及卤代烃的用量也会影响烷基化产物的取代度。氢氧化钠用量过少,其与壳聚糖接触不够,不能满足壳聚糖碱化所需,氢氧化钠用量过多会使副反应增多,取代度下降,产物提纯精制难度增加;卤代烃用量过多会使副反应增多,用量过少不能满足壳聚糖烷基化反应所需。
步骤2)中,所述有机溶剂为二甲基亚砜(DMSO)或二甲基甲酰胺(DMF);
步骤2)中,双亲性壳聚糖溶于有机溶剂中,浓度为0.1-5.0mg·mL-1。
步骤2)中,所述有机溶剂和超纯水体积比6:1~1:6;
步骤2)中,滴加超纯水使组装基元在分子间弱相互作用力(氢键、范德华力、亲疏水作用等)下聚集发生自组装形成胶体;获得的胶束粒径在100nm-1000nm。
步骤2)中,所述透析在水溶液中进行,用透析袋(MW:3500)透析3-7天,除去有机溶剂。透析3-7天,透析的目的是为了除去有机溶剂(DMSO或者DMF),保留合成的产物。有机溶剂是有毒的,本发明用自组装方式形成的胶束制备特点为绿色环保,无毒生物相容性好的全水相乳液,如果里面有有机溶剂的存在,全水相乳液的制备就没有任何应用的优势。所以要将这个有机溶剂透析掉。只保留双亲性壳聚糖,用于后面的组装胶束,稳定全水相乳液。
步骤2)中滴加超纯水可以使AmCS发生自组装形成AmCS CPs的原理是:胶束通过自组装形成的其中一种作用就是疏水作用。前面通过烷基化反应将疏水基团接枝到壳聚糖(CS)的侧链,向其中滴加水就会使得疏水基团彼此靠近聚集以避开水,就是通过疏水物的疏水基与水相互排斥。疏水基一般来说是非极性基,这种排斥作用会使疏水基团相互靠拢,同时使水相互集中并更大程度的结构化,就会自组装形成胶束粒子。
本发明制备双亲性壳聚糖胶体稳定剂的思路是:将壳聚糖与碱和异丙醇发生碱化反应得到壳聚糖碱化单体,再通过N-烷基化反应将疏水基团(正十六烷、辛基、苄基等)引入到壳聚糖侧链,制备不同取代基的AmCS。将AmCS在有机溶剂(DMSO或DMF)中溶解在磁力搅拌下逐滴加入超纯水,使组装基元在分子间弱相互作用力(氢键、范德华力、亲疏水作用等)下发生自发组装聚集;透析除去(DMSO或DMF),得到AmPS CPs。用制备的AmPS CPs稳定剂在均质作用下二次组装到水-水界面,形成稳定的全水相乳液。
本发明提供的一种双亲性壳聚糖胶体稳定剂,采用上述方法制备得到。
本发明提供的双亲性壳聚糖胶体稳定剂,利用N-烷基化反应将疏水基团接枝到壳聚糖侧链制备不同结构的双亲性壳聚糖(AmCS),再通过疏水相互作用诱导自组装形成双亲性壳聚糖胶体(AmCS CPs),作为乳化剂稳定全水相乳液。与线性聚合物乳化剂和传统的合成颗粒乳化剂相比,避免了繁琐的实验合成条件和复杂的制备过程。形成的AmCS CPs的结构及性能可调控性强,可将活性物质负载到水-水两相界面,实现活性物质的多重负载。制备的多功能全水相乳液在食品、化妆品、生物医学等领域具有潜在的应用前景。
本发明提供的一种全水相乳液,利用上述双亲性壳聚糖胶体稳定剂制备得到。
本发明提供的一种全水相乳液的制备方法为:
将聚乙二醇溶于双亲性壳聚糖胶体稳定剂溶液中,获得聚乙二醇溶液;将葡聚糖溶于超纯水中,获得葡聚糖溶液;将聚乙二醇溶液和葡聚糖溶液混合,静置至混合物形成分层的两个宏观相;在均质作用下使其形成全水相乳液。
所述聚乙二醇PEG的分子量为200-20000;
所述葡聚糖Dex的分子量为1000-500000;
所述聚乙二醇溶液中将聚乙二醇浓度范围为1wt%-60wt%;
所述葡聚糖溶液中葡聚糖的浓度范围为1wt%-60wt%;
所述混合,聚乙二醇溶液和葡聚糖溶液的体积比为6:1-1:6;
所述双亲性壳聚糖胶体稳定剂溶液中双亲性壳聚糖胶体稳定剂的浓度为0.1-5.0mg·mL-1。
所述均质作用具体条件为:均质速度为200-10000r·min-1,均质时间为1-5min。
制备的过程是先将壳聚糖碱化,获得壳聚糖碱化单体,再使其与卤代烃(取代基为正十六烷,苄基、辛基等)发生N-烷基化反应,这些疏水基团被引入到壳聚糖的侧链,使改性后壳聚糖具有疏水性。因为有这些取代基的存在,改性后的壳聚糖只能在有机溶剂中溶解。本发明选用了DMSO和DMF。将其在有机溶剂中溶解之后,通过向溶液中滴加水,通过疏水基团的疏水作用诱导其发生自组装形成双亲性壳聚糖胶体。全水相乳液的特点是界面厚度大(几十到几百纳米),表面张力极低(10-1N/m-10-6N/m)。这两个特点会使得一些小分子的表面活性剂等传统的稳定剂不足够跨越整个相界面,达不到稳定全水相乳液的目的。本发明计合成的胶体首先粒径在几百纳米左右,在实例中有胶体粒子的SEM图为证,它的粒径足够横跨双水相乳液的界面起到稳定的作用,之后通过接触角测试证明本发明合成的壳聚糖胶体对两相具有两亲性,可以在界面上稳固存在,阻止两个水相液滴的聚并,从而形成稳定的全水相乳液。再者,本发明合成方法灵活简易,可以将活性物质(酶或者药物)等负载在胶体中,然后通过均质形成全水相乳液,这种方法制备的稳定剂在稳定乳液的同时还能扩展这种全水相乳液界面的应用研究。
与现有技术相比,本发明是基于大分子多级自组装的原理,通过N-烷基化反应将疏水基团引入到壳聚糖侧链,制备不同结构的AmCS,在水溶液中通过自组装形成AmCS CPs,作为稳定全水相乳液的乳化剂;与线性聚合物乳化剂和传统的合成颗粒乳化剂相比,避免了繁琐的实验合成条件和复杂的制备过程。形成的AmCS CPs结构可调控性强,可负载药物和活性物质到全水相界面,实现全水相乳液对活性物质的多重负载,拓展全水相乳液的应用领域。且,本发明是以全水相系统为基础的全水相乳液,这种乳液可用于低卡路里功能食品的研发,食品和生物加工技术中的微型化化学反应器,也可在生物药品,无油化妆品中作为活性载体使用;也可用于人工细胞界面辅助设计、模拟细胞材料、细胞和生物相容微粒子的制备及3D生物打印新型材料的研发设计等领域的功能性应用研究。
附图说明
图1正十六烷改性壳聚糖胶体的扫描电子显微镜图;
图2正十六烷改性壳聚糖胶体与PEG水相和Dex水相的接触角图片;
图3溶在正十六烷改性壳聚糖胶体溶液的20wt%PEG溶液和溶在超纯水的20wt%Dex溶液以体积比VPEG:VDex为1:3形成的全水相系统图片;
图4正十六烷改性壳聚糖胶体稳定的全水相乳液的光学显微镜图片,两相体积比VPEG:VDex为1:3;
图5正十六烷改性壳聚糖胶体稳定的全水相乳液的催化反应动力学;
图6溶在正十六烷改性壳聚糖胶体溶液的20wt%PEG溶液和溶在超纯水的20wt%Dex溶液以体积比VPEG:VDex为3:1形成的全水相系统图片;
图7正十六烷改性壳聚糖胶体稳定的全水相乳液的光学显微镜图片,两相体积比VPEG:VDex为3:1。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚,下面将结合本发明实施例,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作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。
下述实施例中所用的试验材料和试剂等,如无特殊说明,均可从商业途径获得。
实施例中未注明具体技术或条件者,均可以按照本领域内的文献所描述的技术或条件或者按照产品说明书进行。
实施例1
一种双亲性壳聚糖胶体稳定剂的制备方法,包括以下步骤:
1)正十六烷改性壳聚糖的制备:
将2g壳聚糖、2g氢氧化钾和40g异丙醇置于三颈烧瓶之中,匀速搅拌并升温至40℃后恒温2h以使壳聚糖碱化,升温至60℃滴加氯代正十六烷6mL,恒温60℃搅拌反应4h。反应结束后离心分离得到固体,加入30mL蒸馏水,用浓度为2mol·L-1的稀盐酸中和至中性,产物在丙酮中充分沉淀后过滤,用乙醇-水(V:V=7:3)混合溶液洗涤,直至洗出的水中不再有氯离子,再用无水乙醇洗涤,离心分离后在80℃下烘干至恒重,得到具有双亲性的正十六烷改性壳聚糖(NHa-CS)。
2)NHa-CS胶体的制备:
称取0.02g的NHa-CS加入到含10mL DMSO的烧杯中,配成2.0mg·mL-1的NHa-CS溶液,在烧杯中加磁子,放置在恒温磁力搅拌器上搅拌使其充分溶解,溶液在磁力搅拌下逐滴加入超纯水,加水至溶液出现蓝乳光现象即可,用激光灯照射有明显的光亮的通路,即出现丁达尔效应,发生自发组装聚集;将溶液转入透析袋(MW:3500),透析三天,除去DMSO,得到正十六烷改性壳聚糖胶体(NHa-CS CPs)溶液,即双亲性壳聚糖胶体稳定剂,如图1所示。以称取的NHa-CS质量为准,透析之后DMSO去除,溶液中溶剂是水,但NHa-CS质量是不变的,通过旋蒸,定容,控制后续使用胶束的浓度为2mg·mL-1。
利用上述制备的正十六烷改性壳聚糖胶体(NHa-CS CPs)制备全水相乳液,具体制备方法为:
常温下,称取10g的聚乙二醇(PEG,分子量为20kDa)加入到含40g 2mg·mL-1NHa-CSCPs溶液的烧杯中,在烧杯中放入磁子,置于恒温磁力搅拌器上搅拌使其充分溶解,得到溶在NHa-CS CPs溶液的质量分数为20wt%的PEG溶液;称取10g的葡聚糖(Dex,分子量为150kDa),加入到含40g超纯水的烧杯中,在烧杯中放入磁子,将烧杯置于恒温磁力搅拌器上搅拌使其充分溶解,得到质量分数为20wt%的Dex溶液。两相水溶液按体积比VPEG:VDex=1:3,两相混合后总体积为6mL,将PEG溶液和Dex溶液混合于10mL螺口瓶中,静置至混合物会形成分层的两个宏观相,得到PEG/Dex双水相系统,上相富含PEG,下相富含Dex。如图3所示。在均质速度8000r·min-1,均质3min后得到稳定的全水相乳液。经光学显微镜下观察,如图4所示。
图1是根据实例1中所述制备的NHa-CS CPs的扫描电子显微镜图;将制备的NHa-CSCPs稀释100倍,滴加在硅片上,用SEM表征;由图中可以看出NHa-CS CPs是粒径在300nm左右的球形状。它的粒径足够克服全水相乳液界面厚度大的特点。
固体颗粒稳定剂的润湿能力是决定着乳液的稳定性能的重要影响因素,而固体颗粒润湿性能的表征主要手段之一是接触角。图2是NHa-CS CPs与PEG水相和Dex水相的接触角图片,其中(a)是NHa-CS CPs与PEG水相的接触角数据,(b)是NHa-CS CPs与PEG水相的接触角数据。将实施例1中制备的NHa-CS CPs冷冻干燥,用接触角仪表征。通过图中接触角数据可以看到NHa-CS CPs与PEG相和Dex相的接触角均小于90°,证明了NHa-CS CPs对聚合物PEG和Dex的水溶液具有两亲性。
图3是溶在正十六烷改性壳聚糖胶体溶液的20wt%PEG溶液和溶在超纯水的20wt%Dex溶液以体积比(VPEG:VDex)1:3形成的全水相系统图片,从图中可以看出溶在NHa-CS CPs的体积分数小的PEG水相是呈乳光色,体积分数大的Dex水相呈无色透明,两相呈明显的分层宏观相,构成双水相系统。PEG水相分布在上相,Dex水相在下相。
图4是正十六烷改性壳聚糖胶体稳定的全水相乳液的光学显微镜图片,两相体积比VPEG:VDex为1:3由图所知:形成PEG为分散相,Dex为连续相的稳定存在的,平均直径约为100μm的乳液滴。通过观察本发明实施例1中制备的NHa-CS CPs稳定的全水相乳液稳定时间在一周左右。
根据脲酶催化脲素水解时溶液电导不断增加。本发明建立了电导法测脲酶活性和脲素的方法,探究脲酶在纯水溶液以及在全水相乳液液滴内外和界面上的催化情况,具体实验如下:
底物溶液:称1g脲素溶于5mL纯水中,得到200mg·mL-1的脲素。
对比实验1:将脲酶溶于纯水中,取15mL浓度为0.5mg·mL-1脲酶溶液置于螺口瓶中,加入150μL浓度为20mg·mL-1脲素溶液。测量其在90分钟电导率变化。
对比实验2:将5g的PEG溶于20g超纯水中,得到质量浓度为20wt%的PEG水溶液,将0.04g脲酶溶于PEG水溶液中,得到含脲酶浓度为2mg·mL-1的PEG水溶液。将5g的Dex溶于20g超纯水中,得到质量浓度为20wt%的Dex水溶液。取3.75mL含脲酶的PEG水溶液与11.25mL的Dex水溶液混合在螺口瓶中,以8000r·min-1的均质速度,均质3min后得到脲酶在内水相的全水相乳液。向乳液中加入150μL浓度为20mg·mL-1脲素溶液。测量其在90分钟内的电导率变化。
对比实验3:将5g的PEG溶于20g超纯水中,得到质量浓度为20wt%的PEG水溶液。将5g的Dex溶于20g超纯水中,得到质量浓度为20wt%的Dex水溶液,将0.04g脲酶溶于Dex水溶液中,得到含脲酶浓度为2mg·mL-1的Dex水溶液。取3.75mL的PEG水溶液与含脲酶的11.25mL的Dex水溶液混合在螺口瓶中,以8000r·min-1的均质速度,均质3min后得到脲酶在外水相的全水相乳液。向乳液中加入150μL浓度为20mg·mL-1脲素溶液。测量其在90分钟内的电导率变化。
对比实验4:将脲酶溶在NHa-CS CPs中,称0.04g脲酶溶于20mL的NHa-CS CPs溶液中,得到含脲酶浓度为2mg·mL-1的NHa-CS CPs溶液。再将5g的PEG溶于20g的含脲酶的NHa-CS CPs溶液中,得到质量浓度为20wt%的溶于含脲酶的NHa-CS CPs的PEG水溶液。将5g的Dex溶于20g超纯水中,得到质量浓度为20wt%的Dex水溶液。取3.75mL溶于含脲酶的NHa-CSCPs的PEG水溶液与11.25mL的Dex水溶液混合在螺口瓶中,以8000r·min-1的均质速度,均质3min后得到脲酶在界面上的全水相乳液。向乳液中加入150μL浓度为20mg·mL-1脲素溶液。测量其在90分钟内的电导率变化。
图5是基于实施例1制备的全水相乳液在强化酶促反应速率的应用。进一步证明了本发明制备NHa-CS CPs,在稳定全水相乳液的同时,可负载酶等活性物质,实现界面应用研究。
制备的改性壳聚糖胶体作为全水相乳液的乳化剂,可负载活性物质到乳液滴界面,强化了酶促反应的催化效率。
实施例2
一种双亲性壳聚糖胶体稳定剂的制备方法,包括以下步骤:
1)正十六烷改性壳聚糖的制备
将2g壳聚糖、2g氢氧化钾和40g异丙醇置于三颈烧瓶之中,匀速搅拌并升温至40℃后恒温2h以使壳聚糖碱化,升温至60℃滴加氯代十六烷6mL,恒温60℃搅拌反应4h。反应结束后离心分离得到固体,加入30mL蒸馏水,用浓度为2mol·L-1的稀盐酸中和至中性,产物在丙酮中充分沉淀后过滤,用乙醇-水(V:V=7:3)混合溶液洗涤,直至洗出的水中不再有氯离子,再用无水乙醇洗涤,离心分离后在80℃下烘干至恒重,得到NHa-CS。
2)NHa-CS胶体的制备
称取0.02g的NHa-CS加入到含10mL DMSO的烧杯中,配成2.0mg·mL-1的NHa-CS溶液,在烧杯中加磁子,放置在恒温磁力搅拌器上搅拌使其充分溶解,溶液在磁力搅拌下逐滴加入超纯水,至出现溶液呈蓝乳光现象。用激光灯照射有明显的光亮的通路,即丁达尔效应,诱导发生自发组装聚集;将溶液转入透析袋(MW:3500),透析三天,除去DMSO,得到NHa-CS CPs溶液,以称取的NHa-CS质量为准,透析之后DMSO去除,溶液中溶剂是水,但NHa-CS质量是不变的,通过旋蒸,定容,控制后续使用胶束的浓度为2mg·mL-1。
利用上述制备的正十六烷改性壳聚糖胶体(NHa-CS CPs)制备全水相乳液,具体制备方法为:
常温下,称取10g的聚乙二醇(PEG,分子量为20kDa)加入到含40g的2mg·mL-1NHa-CS CPs溶液的烧杯中,在烧杯中放入磁子,置于恒温磁力搅拌器上搅拌使其充分溶解,得到溶在NHa-CS CPs溶液的质量分数为20wt%的PEG溶液;称取10g的葡聚糖(Dex,分子量为150kDa),加入到含40g超纯水的烧杯中,在烧杯中放入磁子,将烧杯置于恒温磁力搅拌器上搅拌使其充分溶解,得到质量分数为20wt%的Dex溶液。两相水溶液按体积比为VPEG:VDex=3:1,两相混合后总体积为6mL,将PEG溶液和Dex溶液混合于10mL螺口瓶中,静置至混合物会形成分层的两个宏观相,得到PEG/Dex双水相系统,上相富含PEG,下相富含Dex。如图6所示。在均质速度6000r·min-1,均质2min后得到稳定的全水相乳液。经光学显微镜下观察,如图7所示。
图6是溶在正十六烷改性壳聚糖胶体溶液的20wt%PEG溶液和溶在超纯水的20wt%Dex溶液以体积比(VPEG:VDex)3:1形成的全水相系统图片,从图中可以看出溶在胶束的体积分数大的PEG水相是呈乳光色,体积分数小的Dex水相呈无色透明,两相呈明显的分层宏观相,构成双水相系统。PEG水相依然是分布在上相,Dex水相在下相。
图7是正十六烷改性壳聚糖胶体稳定的全水相乳液的光学显微镜图片,两相体积比VPEG:VDex为3:1。由图可得出:形成了Dex为分散相,PEG为连续相的稳定存在的,平均直径约为33μm的乳液滴。与实施例1相比,实例2中因为两聚合物水相的变化,形成了内外相相反的全水相乳液。
实施例3
一种双亲性壳聚糖胶体稳定剂的制备方法,包括以下步骤:
1)苄基改性壳聚糖的制备:
将2g壳聚糖、2g氢氧化钾和40g异丙醇三颈烧瓶之中,匀速搅拌并升温至40℃后恒温2h以使壳聚糖碱化,升温至60℃滴加苄基氯6mL,恒温60℃搅拌反应4h,制备N-烷基化壳聚糖。反应结束后离心分离得到固体,加入30mL蒸馏水,用浓度为2mol·L-1的稀盐酸中和至中性,产物在丙酮中充分沉淀后过滤,用乙醇-水(V:V=7:3)混合溶液洗涤,直至洗出的水中不再有氯离子,再用无水乙醇洗涤,离心分离后在80℃下烘干,得到具有双亲性的苄基改性壳聚糖(Benzyl-CS)。
2)Benzyl-CS胶体的制备:
称取0.02g的Benzyl-CS加入到含10mL二甲基甲酰胺(DMF)的烧杯中,配成2mg·mL-1的Benzyl-CS溶液,在烧杯中加磁子,放置在恒温磁力搅拌器上搅拌使其充分溶解,溶液在磁力搅拌下逐滴加入超纯水,至溶液出现蓝乳光现象,用激光灯照射有明显的光亮的通路,即丁达尔效应,诱导发生自发组装聚集;将溶液转入透析袋(MW:3500),透析三天,除去DMF,得到苄基改性壳聚糖胶体(Benzyl-CS CPs)溶液。以称取的Benzyl-CS质量为准,透析之后DMF去除,溶液中溶剂是水,但Benzyl-CS质量是不变的,通过旋蒸,定容,控制后续使用胶束的浓度为2mg·mL-1。
利用上述制备的苄基改性壳聚糖胶体(Benzyl-CS CPs)制备全水相乳液,具体制备方法为:
常温下,称取9g的聚乙二醇(PEG,分子量为20kDa)加入到含41g 2mg·mL-1Benzyl-CS CPs溶液的烧杯中,在烧杯中放入磁子,置于恒温磁力搅拌器上搅拌使其充分溶解,得到溶解在Benzyl-CS CPs溶液中的质量分数为18wt%的PEG溶液;称取9g的葡聚糖(Dex,分子量为150kDa),加入到含41g超纯水的烧杯中,在烧杯中放入磁子,将烧杯置于恒温磁力搅拌器上搅拌使其充分溶解,得到质量分数为18wt%的Dex溶,两相聚合物水溶液按体积比为VPEG:VDex=2:1,两相混合后总体积为6mL,将PEG溶液和Dex溶液混合于10mL螺口瓶中,将混合物静置至混合物会形成分层的两个宏观相,得到PEG/Dex双水相系统。上相富含PEG,下相富含Dex。在均质速度8000r·min-1,均质3min后得到稳定的全水相乳液。
实施例4
一种双亲性壳聚糖胶体稳定剂的制备方法,包括以下步骤:
1)辛基改性壳聚糖的制备:
将1.5g壳聚糖、1.5g氢氧化钾和30g异丙醇置于三颈烧瓶之中,匀速搅拌并升温至40℃后恒温2h以使壳聚糖碱化,升温至60℃滴加氯辛烷6mL,恒温60℃搅拌反应4h,制备N-烷基化壳聚糖。反应结束后离心分离得到固体,加入30mL蒸馏水,用浓度为2mol·L-1的稀盐酸中和至中性,产物在丙酮中充分沉淀后过滤,用乙醇-水(V:V=7:3)混合溶液洗涤,直至洗出的水中不再有氯离子,再用无水乙醇洗涤,离心分离后在80℃下烘干,得到具有双亲性的辛基改性壳聚糖(Octyl-CS)。
2)Octyl-CS胶体的制备:
称取0.02g的Octyl-CS加入到含10mL二甲基甲酰胺(DMF)的烧杯中,配成2mg·mL-1的Octyl-CS溶液,在烧杯中加磁子,放置在恒温磁力搅拌器上搅拌使其充分溶解,溶液在磁力搅拌下逐滴加入超纯水,至溶液出现蓝乳光现象,用激光灯照射有明显的光亮的通路,即出现丁达尔效应,诱导发生自发组装聚集;将溶液转入透析袋(MW:3500),透析三天,除去DMF,得到辛基改性壳聚糖胶体(Octyl-CS CPs)。以称取的Octyl-CS质量为准,透析之后DMF去除,溶液中溶剂是水,但Octyl-CS质量是不变的,通过旋蒸,定容,控制后续使用胶束的浓度为2mg·mL-1。
利用上述制备的辛基改性壳聚糖胶体(Octyl-CS CPs)制备全水相乳液,具体制备方法为:
常温下,称取8g的聚乙二醇(PEG,分子量为20kDa)加入到含42g 2mg·mL-1Octyl-CS CPs溶液的烧杯中,在烧杯中放入磁子,置于恒温磁力搅拌器上搅拌使其充分溶解,得到溶解在Octyl-CS CPs溶液中的质量分数为16wt%的PEG溶液;称取8g的葡聚糖(Dex,分子量为150kDa),加入到含42g超纯水的烧杯中,在烧杯中放入磁子,将烧杯置于恒温磁力搅拌器上搅拌使其充分溶解,得到质量分数为16wt%的Dex溶液,两相聚合物水溶液按体积比为VPEG:VDex=1:1,两相混合后总体积为6mL,将PEG溶液和Dex溶液混合于10mL螺口瓶中,将混合物静置至混合物会形成澄清的两相,得到PEG/Dex双水相系统。上相富含PEG,下相富含Dex。在均质速度8000r·min-1,均质2min后得到稳定的全水相乳液。
Claims (5)
1.一种全水相乳液,其特征在于,利用双亲性壳聚糖胶体稳定剂制备得到;
所述双亲性壳聚糖胶体稳定剂的制备方法包括以下步骤:
1)双亲性壳聚糖的制备:
将壳聚糖、碱和异丙醇混合,匀速搅拌并加热反应使壳聚糖碱化,再继续升温滴加取代基为正十六烷、辛基或苄基的卤代烃,恒温搅拌反应后,制备N-烷基化壳聚糖,反应结束后,离心分离得到固体,纯化、烘干,得到双亲性壳聚糖AmCS;
2)双亲性壳聚糖胶体稳定剂的制备:
将双亲性壳聚糖溶于有机溶剂中,在搅拌下逐滴加入超纯水,至出现丁达尔现象,再透析除去有机溶剂,得到双亲性壳聚糖胶体稳定剂AmCS CPs;
步骤1)中卤代烃与壳聚糖单体的用量摩尔比0.1:1-4.5:1;
步骤2)中,所述有机溶剂为二甲基亚砜或二甲基甲酰胺,双亲性壳聚糖溶于有机溶剂中,浓度为0.1-5.0 mg·mL-1;所述有机溶剂和超纯水体积比6:1~1:6;获得的胶束粒径在100nm-1000nm。
2.根据权利要求1所述的全水相乳液,其特征在于,步骤1)中壳聚糖、碱、异丙醇的质量比为是1:1:20。
3.一种权利要求1或2所述的全水相乳液的制备方法,其特征在于,所述全水相乳液的制备方法为:
将聚乙二醇溶于双亲性壳聚糖胶体稳定剂溶液中,获得聚乙二醇溶液;将葡聚糖溶于超纯水中,获得葡聚糖溶液;将聚乙二醇溶液和葡聚糖溶液混合,静置至混合物形成分层的两个宏观相;在均质作用下使其形成全水相乳液。
4.根据权利要求3所述的制备方法,其特征在于,所述混合,聚乙二醇溶液和葡聚糖溶液的体积比为 6:1-1:6。
5.根据权利要求3或4所述的制备方法,其特征在于,所述均质作用具体条件为:均质速度为 200-10000 r·min-1,均质时间为 1-5 min。
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