CN113423379A - 利用金属-有机骨架材料和三嵌段共聚物的用于透皮递送的复合物 - Google Patents
利用金属-有机骨架材料和三嵌段共聚物的用于透皮递送的复合物 Download PDFInfo
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- CN113423379A CN113423379A CN201980087688.2A CN201980087688A CN113423379A CN 113423379 A CN113423379 A CN 113423379A CN 201980087688 A CN201980087688 A CN 201980087688A CN 113423379 A CN113423379 A CN 113423379A
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Abstract
本发明涉及一种利用金属‑有机骨架材料(MOF)和三嵌段共聚物的用于透皮递送的复合物。此外,本发明涉及一种包含所述用于透皮递送的复合物的化妆品组合物和制备用于透皮递送的复合物的方法。
Description
技术领域
本发明涉及一种利用金属-有机骨架材料(MOF)和三嵌段共聚物的用于透皮递送的复合物。
此外,本发明涉及一种包含所述用于透皮递送的复合物的化妆品组合物。
此外,本发明涉及一种制备所述用于透皮递送的复合物的方法。
本发明是在韩国产业通商资源部的支持下通过课题编号10077704完成的,上述课题的研究管理专门机构为韩国产业技术评价管理院,研究项目名称为材料部件技术开发项目(战略性核心材料开发项目),研究课题名称为可以利用LDH和MOF来提高功能性生理活性物质的皮肤透过率以及控制开始(On)/停止(Off)释放的复合材料的开发,研究时间为2017年04月01日至2019年12月31日。
背景技术
使化妆品的活性(有效)物质渗透至皮肤并不容易。为此,为了稳定活性成分并增加透皮效率,正在努力并积极地研究将透皮递送系统(transdermal delivery system,TDS)用于功能性化妆品。由于功能性材料的开发,正在广泛地研究可以赋予这种材料更高的稳定性的各种功能化方法。
皮肤总是暴露于外部环境中,皮肤是保护身体的重要器官,并且是阻止体液的损失并保护身体免受有害环境侵害的最重要的首道防线。即,皮肤抑制水分和电解质的流失,并提供正常的生化代谢环境,而且起到保护人体免受机械性刺激以及紫外线和各种微生物侵害的屏障功能。皮肤大致分为真皮和表皮,真皮与其下部的皮下脂肪紧密贴合。表皮是上皮组织的一部分,由5个细胞层组成,即由基底细胞层、棘细胞层、颗粒层、透明层和角质层组成。存在于皮肤的最外侧的角质层是起到屏障功能的第一道防护膜。Elias等提出灰浆(角质细胞间脂质)和砖(角质细胞)的两个区划模型之后,开始更加关注角质层和皮肤屏障。即,角质层的角质细胞形成如同堆砌砖块的形状,角质细胞间脂质起到支撑这些角质细胞的如同灰浆的作用。角质层由约40%的蛋白质、40%的水分以及10-20%的脂质组成,其结构由富含蛋白质的角质细胞和填充角质细胞之间的脂质构成,其中,特别是脂质起到主要的屏障作用。角质层中存在被称为天然保湿因子(Natural Moisturizing Factor,NMF)的亲水性的吸湿物质而在皮肤保湿中起到重要的作用。NMF的组成为氨基酸类、吡咯烷酮羧酸、尿素、氨、尿酸、葡萄糖胺、肌酸酐、柠檬酸盐、钠、钾、钙、氯、镁、糖、有机酸、肽等。为了使活性成分的效果极大化,制成比皮肤细胞间脂质之间的100-200nm小或相似的尺寸时才可以更容易地渗透到皮肤深处。
正在积极地研究被称为金属-有机骨架材料(Metal-Organic Framework,MOF)的物质的合成和特性。金属-有机骨架材料是包含金属离子或金属簇的二级结构单元与有机配体配位结合形成的三维晶体多孔物质。目前为止,通过金属二级结构单元与各种有机配体结构的组合,合成了数千种金属-有机骨架材料物质。与现有的作为多孔物质的沸石、活性炭、二氧化硅等相比,金属-有机骨架材料的表面积是所述现有的多孔物质的3倍至7倍左右,并且易于实现化学功能化,因此金属-有机骨架材料作为代替现有的多孔物质的新型物质备受关注。
MOF-5是由美国的Omar M.Yaghi教授于1999年合成的金属-有机骨架材料,所述MOF-5是通过1,4-苯二甲酸(1,4-benzenedicarboxylic acid,BDC)有机配体与Zn4O的二级结构单元之间的配位结合形成的第一个代表性的金属-有机骨架材料。此外,在同一年,中国香港的Williams研究小组通过1,3,5-苯三甲酸(1,3,5-benzenetricarboxylic acid)与Cu2(COOR)4的二级结构单元的组合,合成了新型金属-有机骨架材料HKUST-1。HKUST-1的情况下,合成后溶剂与Cu2+金属配位,在真空下对其进行热处理时,形成开放金属位点(open-metal site,OMS),这像路易斯酸一样起作用,可以与富含电子的化学物质(路易斯碱)相互作用,从而可用于催化剂、气体分离和储存。
合成MOF-5的美国的Yaghi研究小组利用有机合成技术设计并合成了从首次报道的MOF-5结构经过改性的各种MOF。通过调节有机配体的长度,合成了具有与MOF-5相似的结构但空穴尺寸增大的MOF,并且通过使用具有各种官能团的有机配体,成功地将各种官能团引入到MOF结构中。从设计阶段就可以调节所需的物理性能的定制(tailor-made)方式的合成策略可以认为是MOF物质有别于现有的其它多孔物质的非常独特的优点。
法国的Ferey研究小组一直在研究Cr系和Fe系的羧酸盐(carboxylate)MOF并合成MIL系列,而且发表了作为Al和苯三甲酸盐(benzenetricarboxylate,H3BTC)的配位化合物的MIL-53(商标名Basolite A100),并作为催化剂和吸附剂进行了大量研究。此外,根据报道,MIL-101是具有最大5900m2/g的大表面积的多孔物质。
随着有机合成技术的发展,已经合成了各种设计的有机配体,并且通过各种金属和金属簇之间的组合,已报道有数千种MOF和它们的各种特性。美国西北大学的Hupp研究小组通过延长有机配体的长度,合成了作为新型的MOF的Nu-110。通过实验方法和计算化学方法设计了新型配体,并使该配体与硝酸铜(copper nitrate)反应合成了Nu-110。所合成的Nu-110 MOF在现有的MOF物质中具有最大的表面积,其表面积为7100m2/g,这是可以用1g的MOF覆盖整个美式足球场的巨大的表面积。将MOF用于气体的储存和分离或者用于储存能量时,这种高表面积可以发挥非常大的优势。在药物递送系统中,问题在于药物在到达目标身体组织之前迅速分解且其活性降低。因此,正在研究利用载体递送药物以增加药物的活性。利用载体时,药物的稳定性增加,而且具有药物的毒性降低且药物的效率增加等效果,作为有效地递送药物的载体的条件,需要高负载量,防止破裂(burst)现象,调节载体的分解等。目前为止报道的纳米载体有脂质体、纳米乳、纳米颗粒、胶束、二氧化硅等,但这些载体无法满足前面提出的条件。根据M.Vallet-Regi研究小组的结果,特别是二氧化硅的情况下,所负载的药物的储存容量降低。因此,建议MOF作为解决这种问题的方法。MOF是一种结合了大孔容、规则孔隙度和易于控制孔径的优点的物质。在如上所述的思路下,调节MOF的孔结构和化学功能性等时,可以弥补目前使用的载体具有的缺点,从而可以实现高载药量、载体-药物之间的相互作用和适当的释放速度。
Patricia Horcajada研究小组曾尝试应用如下载体,所述载体可以通过调节多孔性有机-金属结构体的结构和孔隙率来提高载药量和载体-药物之间的相互作用。研究小组将多孔性羧酸铁(iron-carboxylate)MOFs用作纳米尺寸的载体,包封具有互相不同的极性和尺寸以及各种官能团的药物。这里使用的羧酸铁MOFs是无毒的且具有生物相容性,因此具有作为载体的优点。此外,在将MOFs浸入溶解有各种药物的溶液中以负载药物的过程中,研究小组使用水或乙醇来代替有机溶剂,从而提高了生物医学方面的应用可能性。
另外,生物降解性高分子是指生物的代谢参与分解的一个过程中而转变为低分子量化合物的高分子物质,它们的生物降解性往往可以通过存在于人的皮肤或其他细胞组织的酶而加速化。生物降解性高分子有源自植物或动物的天然高分子、微生物产生的高分子和合成高分子,代表性的实例有纤维素、普鲁兰多糖、聚谷氨酸、聚乳酸、聚乙醇烯、聚乙二醇、聚氨酯等。生物降解性高分子具有生物相容性和生物降解性等特性,因此作为载体在诸如生物医药、药学以及化妆品的多种领域中受到广泛关注。作为利用这种生物降解性高分子的实例,韩国公开专利公报第10-2014-0098926号中公开了一种缓释剂型和含有其的化妆品组合物,该缓释剂型中通过利用生物降解性高分子而使不稳定的活性成分稳定化,并缓慢释放稳定化的活性成分。
发明内容
要解决的技术问题
因此,本发明要解决的技术问题是提供一种新型的用于透皮递送的复合物,所述复合物可以将活性成分以稳定的状态有效地递送至皮肤中。
此外,本发明要解决的另一个技术问题是提供一种包含所述用于透皮递送的复合物的化妆品组合物。
此外,本发明要解决的另一个技术问题是用于制备所述用于透皮递送的复合物的制备方法。
技术方案
为了解决上述技术问题,本发明提供一种用于透皮递送的复合物,其包含金属-有机骨架材料(metal-organic framework)和聚乙二醇(PEG)-聚己内酯(PCL)-聚乙二醇(PEG)的三嵌段共聚物(triblock copolymer)。
此外,本发明提供一种包含所述用于透皮递送的复合物的化妆品(cosmetic)组合物。
此外,本发明提供一种制备用于透皮递送的复合物的方法,其包括以下步骤:
i)混合金属-有机骨架材料溶液和聚乙二醇(PEG)-聚己内酯(PCL)-聚乙二醇(PEG)的三嵌段共聚物溶液;ii)将所述步骤(i)中获得的溶液进行搅拌或(超)声波(sonication)处理以形成复合物;iii)将所述步骤(ii)中获得的复合物进行干燥,
或包括以下步骤:
i)混合金属-有机骨架材料溶液和聚乙二醇(PEG)-聚己内酯(PCL)-聚乙二醇(PEG)的三嵌段共聚物溶液;ii)将所述步骤(i)中获得的溶液进行(超)声波处理之后进行搅拌以形成复合物;iii)将所述步骤(ii)中获得的复合物进行干燥。
以下,对本发明进行详细说明。
根据本发明的一个方面,提供一种用于透皮递送的复合物,所述复合物包含金属-有机骨架材料和聚乙二醇(PEG)-聚己内酯(PCL)-聚乙二醇(PEG)的三嵌段共聚物。
在本发明中,作为用于透皮递送的复合物的一种成分,包含金属-有机骨架材料(metal-organic framework,MOF)。
金属-有机骨架材料是包含金属离子或金属簇的二级结构单元与有机配体配位结合形成的三维晶体多孔物质。在本发明中,金属-有机骨架材料优选为类沸石咪唑酯骨架材料(zeolitic imidazolate framework,ZIF)。类沸石咪唑酯骨架材料是过渡金属离子(例如,Fe、Co、Cu或Zn)与咪唑(imidazole)连接基团连接而形成的。
在本发明中,类沸石咪唑酯骨架材料优选为ZIF-8。ZIF-8具有锌(Zn)离子与4个咪唑配位结合的结构(图1)。
在本发明中,作为用于透皮递送的复合物的一种成分,包含聚乙二醇(PEG)-聚己内酯(PCL)-聚乙二醇(PEG)的三嵌段共聚物。在本发明中,聚乙二醇(PEG)-聚己内酯(PCL)-聚乙二醇(PEG)的三嵌段共聚物可以根据本领域中公知的方法进行合成,例如,可以用甲氧基聚(乙二醇)(methoxypoly(ethylene glycol),mPEG)和ε-己内酯(ε-caprolactone)形成PEG-PCL的二嵌段共聚物之后对它们进行连接,从而合成PEG-PCL-PEG的三嵌段共聚物(图2)。
在本发明中,PEG-PCL-PEG的三嵌段共聚物与金属-有机骨架材料形成复合物,从而提高透皮递送效果。
在本发明中,优选地,相对于10重量份的金属-有机骨架材料,以0.01-20重量份的PEG-PCL-PEG的三嵌段共聚物形成复合物。本发明的一个具体实施方案中,PEG-PCL-PEG的三嵌段共聚物与ZIF-8的亚胺(imine)基结合。
根据本发明的一个具体实施方案,所述用于透皮递送的复合物进一步包含活性成分。在本发明中,对活性成分不作具体限制。在本发明中,活性成分可以是例如选自保湿剂、美白剂、皱纹改善剂、紫外线阻断剂、毛发生长促进剂、维生素或其衍生物、氨基酸或肽、抗炎剂、痤疮治疗剂、杀菌剂、女性激素、角质松解剂和天然产物中的一种以上,但并不限定于此。
保湿剂的实例包括肌酸、聚谷氨酸、乳酸钠、羟脯氨酸、2-吡咯烷酮-5-羧酸钠、透明质酸、透明质酸钠、神经酰胺、植物甾醇、胆固醇、谷甾醇、蛋白多糖等,但并不限定于此。美白剂的实例包括熊果苷和熊果苷衍生物、曲酸、红没药醇、烟酰胺、维生素C和维生素C衍生物、胎盘、尿囊素等,但并不限定于此。皱纹改善剂的实例包括视黄醇、视黄醇衍生物、腺苷、甘草提取物、红参提取物、人参提取物等,但并不限定于此。紫外线阻断剂的实例包括二苯甲酮衍生物、对氨基苯甲酸衍生物、甲氧基肉桂酸衍生物、水杨酸衍生物等,但并不限定于此。对毛发生长促进剂不作特别限制,但优选为血液循环促进剂和/或毛囊刺激剂,血液循环促进剂的实例包括日本当药提取物、千金藤素、维生素E及其衍生物、γ-谷维素等,但并不限定于此,毛囊刺激剂的实例包括辣椒酊、姜酊、斑蝥酊、烟酸苄酯等,但并不限定于此。维生素或其衍生物例的实例包括维生素A(视黄醇)及其衍生物、维生素B1、维生素B2、维生素B6、维生素E及其衍生物、维生素D、维生素H、维生素K、泛酸及其衍生物、生物素、泛醇、辅酶Q10、艾地苯醌等,但并不限定于此。氨基酸或肽的实例包括胱氨酸、半胱氨酸、蛋氨酸、丝氨酸、赖氨酸、色氨酸、氨基酸提取物、表皮细胞生长因子(EGF)、胰岛素样生长因子(IGF)、成纤维细胞生长因子(FGF)、三肽-1铜、三肽-29、三肽-1、乙酰基六肽-8、烟酰三肽-35、六肽-12、六肽-9、棕榈酰五肽-4、棕榈酰五肽-3、棕榈酰四肽-7、棕榈酰三肽-29、棕榈酰三肽-1、九肽-7、三肽-10瓜氨酸(citrulline)、sh-多肽-15、棕榈酰三肽-5、二氨基丙酰基三肽-33、r-蜘蛛(spider)多肽-1等,但并不限定于此。抗炎剂的实例包括β-甘草次酸、甘草次酸衍生物、氨基己酸、氢化可的松、β-葡聚糖、羟基积雪草苷、甘草等,但并不限定于此。痤疮治疗剂的实例包括雌二醇、雌激素、乙炔雌二醇、三氯生、壬二酸等,但并不限定于此。杀菌剂的实例包括苯扎氯铵、苄索氯铵(benzethonium chloride)、卤卡班等,但并不限定于此。对女性激素不作特别限制,但优选为雌激素,雌激素优选为雌二醇、乙炔雌二醇、作为植物雌激素的异黄酮等。角质松解剂的实例包括硫、水杨酸、AHA、BHA、间苯二酚等,但并不限定于此。天然产物的提取物或由它们获得的成分的实例包括日本金缕梅、野芝麻、白花蛇舌草、掌叶大黄、甘草、芦荟、甘菊、玫瑰果、马栗树、人参、丝瓜、黄瓜、紫菜、裙带菜、薯蓣、蜗牛、零余子、绿茶等的提取物或姜黄素(curcumin)、扁柏酚、β-胡萝卜素等,但并不限定于此。
此外,活性成分还可以使用油、蜡、油脂(butter)、石蜡、诸如硬脂酸等的高级脂肪酸、诸如鲸蜡醇乙基己酸酯等的酯、诸如硅酮等的美容成分。油的实例包括橄榄油、山茶油、鳄梨油、澳洲坚果油、蓖麻油、葵花油、荷荷芭油、扁桃仁油、杏仁油、绿茶油、白池花籽(meadowfoam seed)油或摩洛哥坚果油等,但并不限定于此。蜡的实例包括巴西棕榈蜡、小烛树(candelilla)蜡、荷荷芭油、蜂蜡、羊毛脂、豆蜡、米糠蜡、硅蜡等,但并不限定于此。油脂的实例包括牛油树脂、芒果脂、绿茶脂或豆(soy)脂等,但并不限定于此。碳氢化合物的实例包括液体石蜡、石蜡、凡士林(petrolatum)、地蜡、微晶蜡(microcrystalline wax)或角鲨烷等,但并不限定于此。高级脂肪酸的实例包括月桂酸、肉豆蔻酸、棕榈酸、硬脂酸、异硬脂酸、油酸、亚油酸或亚麻酸等,但并不限定于此。高级醇的实例包括月桂醇、肉豆蔻醇、鲸蜡醇、硬脂醇、油醇或山嵛醇等,但并不限定于此。酯类的实例包括2-辛基十二醇肉豆蔻酸酯、鲸蜡醇2-乙基己酸酯、二异硬脂醇苹果酸酯或鲸蜡醇乙基己酸酯等,但并不限定于此。硅酮的实例包括聚二甲基硅氧烷类、环聚二甲基硅氧烷类、有机硅聚合物类或硅油等,但并不限定于此。
除此之外,还有酵母提取物、胶原蛋白、弹性蛋白、蔗糖八硫酸酯铝、DHA、EPA、香料成分等。
根据本发明的另一个方面,提供一种包含本发明的用于透皮递送的复合物的化妆品组合物。在本发明中,化妆品组合物例如可以配制成爽肤水、乳液、润肤露、面霜、精华素等,但并不限定于此。
化妆品组合物中优选包含1-60重量%的本发明的用于透皮递送的复合物,更优选包含2-50重量%的本发明的用于透皮递送的复合物。在本发明中,当化妆品组合物中包含小于1重量%的用于透皮递送的复合物时,活性成分带来的效果可能甚微,并且即使化妆品组合物中包含超过60重量%的用于透皮递送的复合物,也难以期待活性成分带来的效果与其添加量成比例地增加,因此在经济上不优选。
根据本发明的另一个方面,提供一种制备用于透皮递送的复合物的方法,其包括以下步骤:
i)混合金属-有机骨架材料溶液和聚乙二醇(PEG)-聚己内酯(PCL)-聚乙二醇(PEG)的三嵌段共聚物溶液;ii)将所述步骤(i)中获得的溶液进行搅拌或(超)声波处理以形成复合物;iii)将所述步骤(ii)中获得的复合物进行干燥,
或包括以下步骤:
i)混合金属-有机骨架材料溶液和聚乙二醇(PEG)-聚己内酯(PCL)-聚乙二醇(PEG)的三嵌段共聚物溶液;ii)将所述步骤(i)中获得的溶液进行(超)声波处理之后进行搅拌以形成复合物;iii)将所述步骤(ii)中获得的复合物进行干燥。
在所述制备方法的步骤(i)中,金属-有机骨架材料溶液可以通过将金属-有机骨架材料溶解在溶剂中来获得,例如溶解在纯净水、碳原子数为1至5的无水或含水低级醇或者它们的混合物中来获得。所述金属-有机骨架材料优选为类沸石咪唑酯骨架材料(ZIF)。在本发明中,类沸石咪唑酯骨架材料优选为ZIF-8。
本发明的一个具体实施方案中,ZIF-8可以通过在六水合硝酸锌(zinc nitratehexahydrate)溶液中逐滴加入2-甲基咪唑(2-methylimidazole)溶液并搅拌来制备。
在所述制备方法的步骤(i)中,PEG-PCL-PEG的三嵌段共聚物溶液可以通过将PEG-PCL-PEG的三嵌段共聚物溶解在溶剂中来获得,例如溶解在纯净水、碳原子数为1至5的无水或含水低级醇或者它们的混合物中来获得。
在所述制备方法的步骤(ii)中,将通过混合金属-有机骨架材料溶液和PEG-PCL-PEG的三嵌段共聚物溶液而得到的溶液进行搅拌或(超)声波处理,或者进行(超)声波处理之后进行搅拌时,PEG-PCL-PEG的三嵌段共聚物和金属-有机骨架材料结合形成复合物。本发明的一个具体实施方案中,PEG-PCL-PEG的三嵌段共聚物与ZIF-8的亚胺基结合。
在所述制备方法的步骤(iii)中,所制备的复合物的干燥可以例如通过在60℃以上的高温下真空干燥或冷冻干燥来进行。本发明的一个具体实施方案中,在所述步骤(iii)的干燥之后,可以进一步进行洗涤所制备的复合物的步骤。复合物的洗涤可以例如通过使用乙醇来进行。
有益效果
本发明的用于透皮递送的复合物将活性成分以非常稳定的形式有效地递送至皮肤中,因此以少量的活性成分也可以长时间显示出非常优异的效果。
附图说明
图1是示出ZIF-8的结构的示意图。
图2是示出PEG-PCL-PEG三嵌段共聚物的合成过程的示意图。
图3是使用冷冻电子显微镜对实施例1中制备的ZIF-8-三嵌段共聚物复合物进行放大拍摄的照片。
图4是使用冷冻电子显微镜对实施例4中制备的ZIF-8-三嵌段共聚物复合物进行放大拍摄的照片((a)在25℃下搅拌,(b)在40℃下搅拌)。
图5是示出使用Photal ELS-Z测量ZIF-8-三嵌段共聚物复合物的颗粒直径尺寸的结果的图。
图6是示出为了测量ZIF-8-三嵌段共聚物复合物的稳定性而利用Photal ELS-Z测量Zeta电位的结果的图。
图7是示出利用Turbiscan测量ZIF-8-三嵌段共聚物复合物的稳定度的结果的图。
图8是示出ZIF-8和ZIF-8-三嵌段共聚物复合物的X射线粉末衍射(XRD)光谱的图。
图9是示出通过紫外-可见分光光度法(UV-visible spectrophotometer)对ZIF-8以及实施例1至实施例3中制备的ZIF-8-三嵌段共聚物复合物进行测量的结果的图((a)ZIF-8,(b)实施例1,(c)实施例2,(d)实施例3)。
具体实施方式
以下,通过实施例对本发明进行更具体的说明。但是,以下实施例仅仅是有助于理解本发明的示例,本发明的范围并不限定于此。
制备例1:ZIF-8的制备
制备例1-1:六水合硝酸锌(zinc nitrate hexahydrate)溶液的制备
将0.4g的六水合硝酸锌完全溶解在1.6g的H2O中。此时,利用NaOH将pH调节至8.0后使用H2O,并进行超声波处理5分钟以完全溶解。之后,添加8ml的去离子水,以300RPM搅拌30分钟。
制备例1-2:2-甲基咪唑(2-methylimidazole)溶液的制备
将4.0g的2-甲基咪唑完全溶解在16.0g的去离子水中。此时,为了完全溶解,进行30分钟以上的超声波处理。
制备例1-3:ZIF-8的合成
在制备例1-1的六水合硝酸锌溶液中逐滴加入制备例1-2的2-甲基咪唑溶液,并以300RPM搅拌30分钟。通过该过程,在Zn2+中形成咪唑桥(bridge),并合成配体,从而形成ZIF-8。将形成的ZIF-8进行洗涤,然后在70℃下干燥7小时30分钟。
制备例1-4:ZIF-8的洗涤
利用蒸馏水离心分离2次,然后使用乙醇离心分离2次,以此进行洗涤。此时,离心分离的条件是以4000RPM进行15分钟(Universal 320/德国(Germany))。
制备例2:PEG-PCL-PEG三嵌段共聚物的制备
分为两个步骤制备了聚乙二醇(PEG)-聚己内酯(PCL)-聚乙二醇(PEG)三嵌段共聚物。第一步骤中形成了甲氧基聚(乙二醇)(mPEG)和ε-己内酯(ε-CL)的二嵌段(diblock)共聚物,第二步骤中使用六亚甲基二异氰酸酯(hexamethylene diisocyanate,HMDI)将两个二嵌段共聚物分子进行连接。
首先,使用迪安-斯塔克分离器(Dean stark trap)去除残留水分之后,将8.06g的mPEG完全溶解在80mL的无水甲苯中25分钟,然后真空干燥3小时。然后,分别添加4.03g的作为单体的ε-CL和1.61g的作为催化剂的SnOct2,然后在140℃下反应14小时。然后,将HMDI添加至反应混合物中,并在60℃下反应8小时。将生成物在二乙醚中进行分离,并在真空下去除残留溶剂之后,得到PEG-PCL-PEG三嵌段共聚物。所有反应都在氮气气氛下进行。将PEG-PCL-PEG三嵌段共聚物的合成示意图示于图2中。将合成的PEG-PCL-PEG三嵌段共聚物的重均分子量制备为10000。
实施例1:通过搅拌和高温真空干燥制备复合物
在制备例1-1的六水合硝酸锌溶液中逐滴加入制备例1-2的2-甲基咪唑溶液,并在300RPM下搅拌15分钟。搅拌结束后,按照下表1的组成,将用制备例2中合成的PEG-PCL-PEG三嵌段共聚物在乙醇中制成的5%的溶液分别进行添加,然后在300RPM下搅拌15分钟。洗涤后在70℃下真空干燥7小时30分钟。
[表1]
实施例1-1 | 实施例1-2 | 实施例1-3 | 实施例1-4 | 实施例1-5 | |
ZIF-8溶液 | 29ml | 27ml | 25ml | 23ml | 20ml |
三嵌段共聚物溶液 | 1ml | 3ml | 5ml | 7ml | 10ml |
实施例2:通过超声波处理和高温真空干燥制备复合物
在制备例1-1的六水合硝酸锌溶液中添加制备例1-2的2-甲基咪唑溶液,然后在25℃下进行超声波处理15分钟。超声波处理结束后,按照下表2的组成,将用制备例2中合成的PEG-PCL-PEG三嵌段共聚物在乙醇中制成的5%的溶液分别进行添加,然后在25℃下进行超声波处理15分钟。洗涤后在70℃下真空干燥7小时30分钟。
[表2]
实施例2-1 | 实施例2-2 | 实施例2-3 | 实施例2-4 | 实施例2-5 | |
ZIF-8溶液 | 29ml | 27ml | 25ml | 23ml | 20ml |
三嵌段共聚物溶液 | 1ml | 3ml | 5ml | 7ml | 10ml |
实施例3:通过超声波处理和冷冻干燥制备复合物
在制备例1-1的六水合硝酸锌溶液中添加制备例1-2的2-甲基咪唑溶液,然后在25℃下进行超声波处理15分钟。超声波处理结束后,按照下表3的组成,将用制备例2中合成的PEG-PCL-PEG三嵌段共聚物在乙醇中制成的5%的溶液分别进行添加,然后在25℃下进行超声波处理15分钟。洗涤后在-120℃下冷冻至少3小时以上,然后干燥两天。
[表3]
实施例3-1 | 实施例3-2 | 实施例3-3 | 实施例3-4 | 实施例3-5 | |
ZIF-8溶液 | 29ml | 27ml | 25ml | 23ml | 20ml |
三嵌段共聚物溶液 | 1ml | 3ml | 5ml | 7ml | 10ml |
实施例4:超声波处理之后通过搅拌和高温真空干燥制备复合物
将用ZIF-8在乙醇中制成的1%的溶液和用PEG-PCL-PEG三嵌段共聚物在乙醇中制成的1%的溶液以50:50(47g:47g)进行混合,然后进行超声波处理20分钟,然后将一个样品在25℃下以300rpm搅拌17小时,并将另一个样品在40℃下以300rpm搅拌17小时,然后在70℃下真空干燥7小时。
实施例5:含有视黄醇的ZIF-8-三嵌段共聚物复合物的制备
将47g的用ZIF-8在乙醇中制成的1%的溶液、47g的用PEG-PCL-PEG三嵌段共聚物在乙醇中制成的1%的溶液以及6g的视黄醇进行混合,并进行超声波处理20分钟,然后在40℃下以300rpm搅拌17小时之后在70℃下真空干燥7小时。
实施例6:含有植物天然产物的ZIF-8-三嵌段共聚物复合物的制备
根据下表4的组成,通过与实施例5相同的方法进行制备。
[表4]
实施例7:含有海洋天然产物的ZIF-8-三嵌段共聚物复合物的制备
根据下表5的组成,通过与实施例5相同的方法进行制备。
[表5]
实施例8:含有油的ZIF-8-三嵌段共聚物复合物的制备
根据下表6的组成,通过与实施例5相同的方法进行制备。
[表6]
实施例9:含有蜡的ZIF-8-三嵌段共聚物复合物的制备
根据下表7的组成,通过与实施例5相同的方法进行制备。
[表7]
实施例10:含有油脂的ZIF-8-三嵌段共聚物复合物的制备
根据下表8的组成,通过与实施例5相同的方法进行制备。
[表8]
实施例11:含有石蜡的ZIF-8-三嵌段共聚物复合物的制备
根据下表9的组成,通过与实施例5相同的方法进行制备。
[表9]
实施例12:含有高级脂肪酸的ZIF-8-三嵌段共聚物复合物的制备
根据下表10的组成,通过与实施例5相同的方法进行制备。
[表10]
实施例13:含有酯的ZIF-8-三嵌段共聚物复合物的制备
根据下表11的组成,通过与实施例5相同的方法进行制备。
[表11]
实施例14:含有硅酮的ZIF-8-三嵌段共聚物复合物的制备
根据下表12的组成,通过与实施例5相同的方法进行制备。
[表12]
实施例15:含有保湿剂的ZIF-8-三嵌段共聚物复合物的制备
根据下表13的组成,通过与实施例5相同的方法进行制备。
[表13]
实施例16:含有美白剂的ZIF-8-三嵌段共聚物复合物的制备
根据下表14的组成,通过与实施例5相同的方法进行制备。
[表14]
实施例17:含有紫外线阻断剂的ZIF-8-三嵌段共聚物复合物的制备
根据下表15的组成,通过与实施例5相同的方法进行制备。
[表15]
实施例18:含有维生素的ZIF-8-三嵌段共聚物复合物的制备
根据下表16的组成,通过与实施例5相同的方法进行制备。
[表16]
实施例19:含有氨基酸的ZIF-8-三嵌段共聚物复合物的制备
根据下表17的组成,通过与实施例5相同的方法进行制备。
[表17]
实施例20:含有肽的ZIF-8-三嵌段共聚物复合物的制备
根据下表18的组成,通过与实施例5相同的方法进行制备。
[表18]
实施例21:含有抗炎剂的ZIF-8-三嵌段共聚物复合物的制备
根据下表19的组成,通过与实施例5相同的方法进行制备。
[表19]
实施例22:含有痤疮治疗剂的ZIF-8-三嵌段共聚物复合物的制备
根据下表20的组成,通过与实施例5相同的方法进行制备。
[表20]
实施例23:含有杀菌剂的ZIF-8-三嵌段共聚物复合物的制备
根据下表21的组成,通过与实施例5相同的方法进行制备。
[表21]
实验例1:冷冻电子显微镜拍摄
对实施例1及实施例4中制备的ZIF-8-三嵌段共聚物复合物进行了拍摄。由于颗粒尺寸非常微小,无法利用普通的光学显微镜进行测量,因此利用冷冻电子显微镜(JEM1010,JEOL公司,日本)进行了拍摄(图3和图4)。
实验例2:颗粒分布的测量
使用Photal ELS-Z测量实施例1-3中制备的ZIF-8-三嵌段共聚物复合物的颗粒分布,并示于图5中。根据测量结果可以知道,复合物的平均颗粒尺寸为281.8nm。
实验例3:ZIF-8-三嵌段共聚物复合物的稳定性的测量
为了测量实施例1-3中制备的ZIF-8-三嵌段共聚物复合物的稳定性,利用PhotalELS-Z测量了Zeta电位,并将其结果示于图6中。根据测量结果可以知道,颗粒的电位为-63.65mV,该复合物是稳定的。
实验例4:ZIF-8-三嵌段共聚物复合物的稳定度的测量
为了测量实施例1-3中制备的ZIF-8-三嵌段共聚物复合物的稳定度,使用Turbiscan进行了测量,根据测量结果可以知道随着时间的经过,△T、△BS几乎没有变化,因此复合物是稳定的(图7)。
实验例5:X射线粉末衍射试验
对制备例1中制备的ZIF-8和实施例4中制备的ZIF-8-三嵌段共聚物复合物进行X射线粉末衍射试验(XRD),并将其结果示于图8中。从图8的结果可以看出,显示出恒定的峰,因此可以知道很好地合成了各个复合物。
实验例6:紫外-可见分光光度法(UV-visible spectrophotometry)试验
通过紫外-可见分光光度法对制备例中制备的ZIF-8和实施例1至实施例3中制备的ZIF-8-三嵌段共聚物复合物进行测量,并将其结果示于图9中。
实验例7:ZIF-8-三嵌段共聚物复合物的促进透皮吸收的效果的实验
根据下表22的组成,分别制备具有含有10%的视黄醇的ZIF-8-三嵌段共聚物复合物的脂质体(脂质体A)和普通脂质体(脂质体B)。
[表22]
(单位:重量%)
将人造皮肤Neoderm(Tego Science公司)安装到弗兰兹型扩散池(Franz-typediffusion cell)(Lab fine instruments公司,韩国)并进行实验。在弗兰兹型扩散池的接收(receptor)池(5ml)中加入50mM的磷酸盐缓冲液(pH为7.4,0.1M的NaCl),然后在32℃下,将扩散池(diffusion cell)以600rpm进行混合并分散,并将50μl的脂质体A和50μl的脂质体B分别加入供给(donor)池中。按照预定的时间进行吸收和扩散,并且使发生吸收和扩散的皮肤为0.64cm2。有效成分的吸收和扩散结束后,利用干燥的低尘擦拭纸(kimwipes)或10ml的乙醇洗掉未被吸收并残留在皮肤上的残留物,并使用尖端型均质机(homogenizer),将吸收并扩散有有效成分的皮肤进行磨碎,然后使用4ml的二氯甲烷提取被吸收到皮肤内部的视黄醇。之后,利用0.45μm的尼龙膜(nylon membrane)滤膜对提取液进行过滤,并通过高效液相色谱(HPLC)法在以下条件下测量视黄醇的含量,然后将结果示于表23中。
[表23]
从所述表23可以看出,在本发明中视黄醇被包封在ZIF-8-三嵌段共聚物复合物中并有效地被递送到皮肤中。
Claims (31)
1.一种用于透皮递送的复合物,其包含金属-有机骨架材料和聚乙二醇(PEG)-聚己内酯(PCL)-聚乙二醇(PEG)的三嵌段共聚物。
2.根据权利要求1所述的用于透皮递送的复合物,其特征在于,所述金属-有机骨架材料是类沸石咪唑酯骨架材料(ZIF)。
3.根据权利要求2所述的用于透皮递送的复合物,其特征在于,所述类沸石咪唑酯骨架材料是ZIF-8。
4.根据权利要求3所述的用于透皮递送的复合物,其特征在于,所述ZIF-8的亚胺基与PEG-PCL-PEG的三嵌段共聚物结合。
5.根据权利要求1所述的用于透皮递送的复合物,其特征在于,相对于10重量份的所述金属-有机骨架材料,所述复合物包含0.01-20重量份的PEG-PCL-PEG的三嵌段共聚物。
6.根据权利要求1所述的用于透皮递送的复合物,其特征在于,所述复合物进一步包含活性成分。
7.根据权利要求6所述的用于透皮递送的复合物,其特征在于,所述活性成分是选自保湿剂、美白剂、皱纹改善剂、紫外线阻断剂、毛发生长促进剂、维生素或其衍生物、氨基酸或肽、抗炎剂、痤疮治疗剂、杀菌剂、女性激素、角质松解剂和天然产物中的一种以上。
8.根据权利要求7所述的用于透皮递送的复合物,其特征在于,所述保湿剂是选自肌酸、聚谷氨酸、乳酸钠、羟脯氨酸、2-吡咯烷酮-5-羧酸钠、透明质酸、透明质酸钠、神经酰胺、植物甾醇、胆固醇、谷甾醇、普鲁兰多糖和蛋白多糖中的一种以上。
9.根据权利要求7所述的用于透皮递送的复合物,其特征在于,所述美白剂是选自熊果苷和熊果苷衍生物、曲酸、红没药醇、烟酰胺、维生素C和维生素C衍生物、胎盘和尿囊素中的一种以上。
10.根据权利要求7所述的用于透皮递送的复合物,其特征在于,所述皱纹改善剂是选自视黄醇、视黄醇衍生物、腺苷、甘草提取物、红参提取物和人参提取物中的一种以上。
11.根据权利要求7所述的用于透皮递送的复合物,其特征在于,所述紫外线阻断剂是选自二苯甲酮衍生物、对氨基苯甲酸衍生物、甲氧基肉桂酸衍生物和水杨酸衍生物中的一种以上。
12.根据权利要求7所述的用于透皮递送的复合物,其特征在于,所述毛发生长促进剂是血液循环促进剂或毛囊刺激剂。
13.根据权利要求12所述的用于透皮递送的复合物,其特征在于,所述血液循环促进剂是选自日本当药提取物、千金藤素、维生素E及其衍生物和γ-谷维素中的一种以上。
14.根据权利要求12所述的用于透皮递送的复合物,其特征在于,所述毛囊刺激剂是选自辣椒酊、姜酊、斑蝥酊和烟酸苄酯中的一种以上。
15.根据权利要求7所述的用于透皮递送的复合物,其特征在于,所述维生素或其衍生物是选自维生素A及其衍生物、维生素B1、维生素B2、维生素B6、维生素E及其衍生物、维生素D、维生素H、维生素K、泛酸及其衍生物、生物素、泛醇、辅酶Q10和艾地苯醌中的一种以上。
16.根据权利要求7所述的用于透皮递送的复合物,其特征在于,所述氨基酸或肽是选自胱氨酸、半胱氨酸、蛋氨酸、丝氨酸、赖氨酸、色氨酸、氨基酸提取物、表皮细胞生长因子(EGF)、胰岛素样生长因子(IGF)、成纤维细胞生长因子(FGF)、三肽-1铜、三肽-29、三肽-1、乙酰基六肽-8、烟酰三肽-35、六肽-12、六肽-9、棕榈酰五肽-4、棕榈酰四肽-7、棕榈酰三肽-29、棕榈酰三肽-1、九肽-7、三肽-10瓜氨酸、sh-多肽-15、棕榈酰三肽-5、二氨基丙酰基三肽-33和r-蜘蛛多肽-1中的一种以上。
17.根据权利要求7所述的用于透皮递送的复合物,其特征在于,所述抗炎剂是选自β-甘草次酸、甘草次酸衍生物、氨基己酸、氢化可的松、β-葡聚糖和甘草中的一种以上。
18.根据权利要求7所述的用于透皮递送的复合物,其特征在于,所述痤疮治疗剂是选自雌二醇、雌激素、乙炔雌二醇、三氯生和壬二酸中的一种以上。
19.根据权利要求7所述的用于透皮递送的复合物,其特征在于,所述杀菌剂是选自苯扎氯铵、苄索氯铵和卤卡班中的一种以上。
20.根据权利要求7所述的用于透皮递送的复合物,其特征在于,所述女性激素是选自雌二醇、乙炔雌二醇和异黄酮中的一种以上。
21.根据权利要求7所述的用于透皮递送的复合物,其特征在于,所述角质松解剂是选自硫、水杨酸、AHA、BHA和间苯二酚中的一种以上。
22.根据权利要求7所述的用于透皮递送的复合物,其特征在于,所述天然产物是选自日本金缕梅提取物、野芝麻提取物、白花蛇舌草提取物、掌叶大黄提取物、甘草提取物、芦荟提取物、甘菊提取物、玫瑰果提取物、马栗树提取物、人参提取物、丝瓜提取物、黄瓜提取物、紫菜提取物、裙带菜提取物、薯蓣提取物、蜗牛提取物、零余子提取物、扁柏酚和β-胡萝卜素中的一种以上。
23.一种化妆品组合物,其包含权利要求6至22中任一项所述的用于透皮递送的复合物。
24.根据权利要求23所述的化妆品组合物,其特征在于,所述化妆品组合物包含1-60重量%的所述用于透皮递送的复合物。
25.一种制备用于透皮递送的复合物的方法,其包括以下步骤:
i)混合金属-有机骨架材料溶液和聚乙二醇(PEG)-聚己内酯(PCL)-聚乙二醇(PEG)的三嵌段共聚物溶液;
ii)将所述步骤(i)中获得的溶液进行搅拌或(超)声波处理以形成复合物;
iii)将所述步骤(ii)中获得的复合物进行干燥。
26.一种制备用于透皮递送的复合物的方法,其包括以下步骤:
i)混合金属-有机骨架材料溶液和聚乙二醇(PEG)-聚己内酯(PCL)-聚乙二醇(PEG)的三嵌段共聚物溶液;
ii)将所述步骤(i)中获得的溶液进行(超)声波处理之后进行搅拌以形成复合物;
iii)将所述步骤(ii)中获得的复合物进行干燥。
27.根据权利要求25或26所述的制备用于透皮递送的复合物的方法,其特征在于,所述金属-有机骨架材料是类沸石咪唑酯骨架材料。
28.根据权利要求27所述的制备用于透皮递送的复合物的方法,其特征在于,所述类沸石咪唑酯骨架材料是ZIF-8。
29.根据权利要求25或26所述的制备用于透皮递送的复合物的方法,其特征在于,所述步骤(iii)中进行60℃以上的高温真空干燥或冷冻干燥。
30.根据权利要求25或26所述的制备用于透皮递送的复合物的方法,其特征在于,在所述步骤(iii)后,进一步包括洗涤所述复合物的步骤。
31.根据权利要求30所述的制备用于透皮递送的复合物的方法,其特征在于,使用乙醇进行洗涤。
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KR20160057189A (ko) * | 2014-11-13 | 2016-05-23 | 주식회사 엘지생활건강 | 폴리페놀계 유효 성분 안정화용 조성물 |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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Non-Patent Citations (1)
Title |
---|
ZHOU,W. ET AL: "Selenium-containing polymer@ metal-organic frameworks nanocomposites an efficient multiresponsive drug delivery system" * |
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