CN103327965B - 脂质体和包含脂质体的个人护理组合物 - Google Patents
脂质体和包含脂质体的个人护理组合物 Download PDFInfo
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- CN103327965B CN103327965B CN201180065780.2A CN201180065780A CN103327965B CN 103327965 B CN103327965 B CN 103327965B CN 201180065780 A CN201180065780 A CN 201180065780A CN 103327965 B CN103327965 B CN 103327965B
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- liposome
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- aqueous dispersion
- phosphatide
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Abstract
本发明公开了脂质体,其包含磷脂、包含羧酸根基团的疏水性活性物质、和选自以下的组分:包含带正电基团的亲水性辅助剂、所述疏水性活性物质与所述亲水性辅助剂的复合物、以及它们的组合。脂质体的含水分散体包含所述脂质体,并且个人护理组合物包含所述脂质体。制备所述脂质体的方法,所述方法包括以下步骤:通过将磷脂、包含羧酸根基团的疏水性活性物质溶解在有机溶剂中形成预混物;从所述预混物中蒸发掉所述有机溶剂以形成磷脂膜;并且用包含具有带正电基团的亲水性辅助剂的水合介质使所述脂质膜水合,并且均化所述介质以形成脂质体的含水分散体。
Description
发明领域
本发明涉及改善疏水性活性物质到皮肤中的递送的脂质体、涉及脂质体的含水分散体、涉及包含脂质体的个人护理组合物、并且涉及制备脂质体的方法。
背景技术
在美容应用中,常常期望局部递送皮肤活性物质到皮肤深层中,即透过角质层到真皮层中。然而,完好无损的皮肤对透过角质层递送皮肤活性物质构成主要障碍。角质层由角质细胞组成,该角质细胞嵌入由组织化的脂质双层组成的脂质基质中,其中脂质物质充当额外的细胞间胶粘物,起到密封角质层中细胞的间隙的作用。
已经开发出多种方法以便透过完好无损的皮肤递送皮肤活性物质。其中一种方法是使用疏水性介质如乳液中的油相破坏或液化角质层中的脂质双层,从而促进活性物质的渗透。
另一种方法是使用囊泡系统如脂质体。脂质体为由磷脂双层组成的囊泡。磷脂分子具有一个极性“头部”和两个非极性“尾部”。由于它的结构,磷脂趋于形成囊泡双层,即脂质体,其中磷脂的极性头部朝向内部或外部的水相对齐,而非极性尾部彼此相向对齐。此类脂质体已用于构建递送活性物质的载体。
然而,有效地截留活性物质进入脂质体并保持此类脂质体的稳定性仍可能是一个挑战。已知在工业中需截留的活性物质的化学性质影响截留效率和相关的脂质体填塞率。包含羧酸根基团如甘草次酸的疏水性活性物质带来这一挑战。
因此,需要在其中可配制包含羧酸根基团的疏水性活性物质的脂质体。脂质体应是稳定的并具有令人满意的此类疏水性活性物质的填塞率,从而改善地渗透到深层皮肤中,并因此在皮层内具有改善的活性物质残留量。
虽然许多人寻求改善疏水性活性物质的脂质体递送,在本领域未见并且未公开本发明的有益效果。参见例如美国专利5,569,464,其涉及包封亲水性或疏水性药物的含水分散体,其中含水分散体包含脂质体、羟酸、和作为稳定剂的氨基酸,以及EP专利0211647B1,其涉及包含水合剂和脂质体形成材料的脂质体形成组合物。
发明内容
本发明涉及脂质体,其包含a)磷脂,b)包含羧酸根基团的疏水性活性物质,和c)组分,其选自:包含带正电基团的亲水性辅助剂,所述疏水性活性物质与所述亲水性辅助剂的复合物,以及它们的组合。本发明还涉及脂质体的含水分散体,并且涉及包含脂质体的个人护理组合物。本发明还涉及制备本发明脂质体的方法,所述方法包括以下步骤:通过将磷脂和包含羧酸根基团的疏水性活性物质溶解在有机溶剂中形成预混物;从所述预混物中蒸发除去所述有机溶剂以形成磷脂膜;所述膜与包含具有带正电基团的亲水性辅助剂的水合介质水合,并且均化所述水合介质以形成脂质体的含水分散体。
附图说明
图1示出了实例1-4和比较例1脂质体、以及比较例2霜膏的填塞率比较。
图2示出了根据8小时内GA渗透通过大鼠皮肤的实例3脂质体和比较例2霜膏的比较。
图3示出了根据在8小时渗透后大鼠皮肤内的GA残留量的实例3脂质体和比较例2霜膏的比较。
具体实施方式
虽然本说明书通过特别指出并清楚地要求保护本发明的权利要求书作出结论,但据信由下列说明可更好地理解本发明。
除非另外指明,所有的百分比、份数和比例均基于脂质体的含水分散体的总重量。所有与所列成分相关的此类重量均基于活性物质的含量计,并因此不包括可能包含在可商购获得的原料中的载体或副产物。
可用于本发明的所有成分如活性物质和其它成分可根据其美容和/或治疗有益效果或其假定的作用模式来分类或描述。然而应当理解,在某些情况下,可用于本发明的活性物质和其它成分可以提供一种以上的美容和/或治疗有益效果,或通过一种以上的作用方式起作用。因此,本文的分类只是为了方便起见,而非旨在将成分限制在所列的特别指出的一个应用或几个应用中。
如本文所用,“脂质体”用于描述包含一个或多个围绕内部水相的天然或合成脂质双层的复层脂质囊泡。
如本文所用,“疏水性活性物质”是指它的辛醇/水分配系数指数的对数值大于零,优选地从0-8,更优选地从1-7的活性物质。疏水性活性物质包含了在它形成脂质体时的pH下可分离的羧酸根基团,这是指羧酸根基团可为羧酸基团或其盐。
如本文所用,“亲水性辅助剂”是指辅助剂的辛醇/水分配系数指数的对数值小于零。
如本文所用,“带正电的基团”是指亲水性辅助剂在本发明脂质体的含水分散体的pH条件下,例如在pH7.0下包含带正电荷的基团。
如本文所用,“弹性脂质体”是指脂质体当渗透通过皮肤阻隔时趋于发生形状改变。
本发明涉及包含磷脂、具有羧酸根基团的疏水性活性物质、和具有带正电基团的亲水性辅助剂的脂质体。本发明的脂质体可以脂质体的含水分散体形式制备。也可将本发明的脂质体掺入个人护理组合物中,其选自霜膏、乳液、凝胶、洗剂、爽肤水、以及它们的组合。
磷脂
本发明的脂质体包含磷脂。磷脂可选自天然磷脂、合成磷脂、以及它们的组合。卵磷脂为其中一种天然来源的磷脂。卵磷脂是存在于蛋黄和大豆等物质中的混合物。它包含多种磷脂,包括磷脂酰胆碱(PC)、磷脂酰乙醇胺(PE)、和磷脂酰肌醇(PI)。天然磷脂也包括例如氢化大豆PC(HSPC)、鞘磷脂、和磷脂酰甘油(PG)。
合成磷脂包括但不限于胆碱磷酸衍生物(例如DDPC、DLPC、DMPC、DPPC、DSPC、DOPC、POPC、DEPC)、磷酸甘油衍生物(例如DMPG、DPPG、DSPG、POPG)、磷脂酸衍生物(例如DMPA、DPPA、DSPA)、磷酸乙醇胺衍生物(例如DMPE、DPPE、DSPE DOPE)、磷酸丝氨酸衍生物(例如DOPS)、磷脂PEG衍生物(例如mPEG-磷脂、聚甘油-磷脂、官能化磷脂、和末端活化磷脂)。对应于上述缩写的磷脂衍生物的化学名可见于网页http://en.wikipedia.org/wiki/ Phospholipid。
在本发明的一个实施例中,磷脂为氢化的磷脂,具体地为氢化大豆PC(HSPC)。
脂质体包含以脂质体的含水分散体重量计约1重量%、3重量%或6重量%至约8重量%、10重量%或20重量%的磷脂。
本发明的脂质体可任选地包括甾体化合物。甾体化合物能够有助于提高脂质双层的稳定性并减少脂质体的渗漏问题。
疏水性活性物质
本发明的脂质体包含具有羧酸根基团的疏水性活性物质。
在一个实施例中,除了羧酸根基团之外,疏水性活性物质还包含具有至少一个芳基的疏水结构域。在一个实施例中,疏水结构域包含多个芳基。优选地,芳基和羧酸根基团位于疏水性活性物质的两个相对端。示例性的疏水性活性物质选自甘草次酸(GA)、甘草亭酸硬脂酸酯、甘草酸十一碳烯酰基苯丙氨酸(商品名SepiwhiteTM)、视黄酸、以及它们的组合。
甘草次酸是一种提供美白有益效果的活性物质。如下所示,它的结构式包括在一端的疏水性多芳基和在另一端的亲水性羧酸根基团。
十一碳烯酰基苯丙氨酸为改性苯丙氨酸,具有如下所示的结构式。它包括在一端的疏水性芳基和在另一端的亲水性羧酸根基团。
适宜的疏水性活性物质可包括在化妆品工业和/或药物工业中使用的那些。
疏水性活性物质在本发明脂质体中的含量为以脂质体的含水分散体重量计约0.01重量%、0.05重量%、0.1重量%、0.3重量%、0.6重量%或0.9重量%至约1.2重量%、1.5重量%或5重量%。作为另外一种选择,疏水性活性物质的量也可基于在构建脂质体中使用的磷脂的量,通常为以磷脂的重量计约1重量%至约20重量%。
亲水性辅助剂
脂质体包含具有带正电基团的亲水性辅助剂。带正电的基团能够与疏水性活性物质的羧酸根基团相互作用以形成复合物。带正电的基团优选地为带正电的氨基(-NH3 +)。在一个实施例中,本发明脂质体的亲水性辅助剂在一端包含一个带正电的基团,并且在与带正电的一端相对的另一端包含一个羧酸根基团。在本发明的另一个实施例中,亲水性辅助剂选自赖氨酸(式I)、精氨酸(式II)、组氨酸(式III)、以及它们的组合。
据信,亲水性辅助剂的带正电的基团与疏水性活性物质的羧酸根基团形成复合物。亲水性辅助剂的非复合端部和芳基端部疏水性活性物质使形成的复合物在性质上为两性的。例如,甘草次酸和赖氨酸形成的复合物的结构在下式IV中示出。
不受理论的约束,据信亲水性辅助剂和疏水性活性物质形成的两性复合物有助于保持使其自身稳定地插入脂质体双层壁的磷脂之间并可能进一步影响脂质体的弹性。通过本发明的脂质体可改善填塞率,并因此改善疏水性活性物质向皮层中的渗透以及在皮层中的残留量。
亲水性辅助剂在本发明脂质体中的含量为以脂质体的含水分散体重量计约0.05重量%、0.3重量%、0.8重量%或1重量%至约1.5重量%、2重量%、8重量%或10重量%。
作为另外一种选择,亲水性辅助剂的量也可基于在构建脂质体中使用的磷脂的量,通常为以磷脂的重量计约1重量%至约20重量%。亲水性辅助剂与疏水性活性物质的摩尔比为约1/10、1/4、1/2或1至约2、4或10。
弹性增强剂
本发明的脂质体优选地为包含弹性增强剂的弹性脂质体。弹性增强剂可选自胆酸钠、脱氧胆酸钠、聚山梨醇酯80(Tween80)、脱水山梨糖醇单油酸酯(Span80)、油酸、甘草酸二钾盐(KG)和胆固醇醚、以及它们的组合。在一个实施例中,弹性增强剂为表面活性剂,例如阴离子表面活性剂、非离子表面活性剂或两性离子表面活性剂,优选非离子表面活性剂。优选地,非离子表面活性剂为Tween80、Span-80和/或聚氧乙烯胆固醇醚,其具有式C27H45O(CH2CH2O)nH,其中n为5至15,例如5、10或15。
在本发明中,弹性增强剂的含量为以脂质体的含水分散体重量计约0.01重量%、0.1重量%或0.4重量%至约2.5重量%、5重量%或10重量%。
其它成分
本发明的脂质体可任选地包含以脂质体的含水分散体重量计约0.01重量%或0.1重量%至约2重量%或5重量%的抗氧化剂。抗氧化剂可选自维生素E、维生素E酯、维生素C、维生素C酯和它们的组合。在一个优选的实施例中,脂质体包含维生素E乙酸酯。
制备方法
本发明的脂质体可按照下文所述步骤制备成脂质体的含水分散体。首先,在70℃下,在容器中,将包括磷脂和疏水性活性物质的所有疏水性材料完全溶解于适宜的有机溶剂中,形成预混物,所述有机溶剂是化妆品和药物工业中脂质体制备可接受的,例如乙醇。可在真空及室温下过夜以除去痕量溶剂。然后从预混物中除去有机溶剂,例如通过旋转真空蒸发。在除去溶剂后,在容器底部形成沉积的磷脂膜。包含亲水性辅助剂的含水介质如磷酸盐缓冲溶液(PBS)用于使膜水合。在水合后,均化含水介质以形成脂质体的含水分散体。可通过恒速搅拌、随后通过超声处理或通过可商购获得的匀化器如购自Avestin,Canada的Emulsiflex C5完成均化。水合介质的选择、用于形成脂质体的水合方式和均化方式是本领域通常已知的。脂质体的含水分散体形成并可在室温下储存。
测量方法
填塞率
填塞率用于测量成功地包封到脂质体中的疏水性活性物质相对于初始加入到有机溶剂中以制备脂质体的含水分散体的疏水性活性物质总量的百分比。将填塞率计算为截留效率(EE%)=CS/CU×100%。
CS代表填塞到脂质体中的疏水性活性物质的量。首先从脂质体的含水分散体中除去未填塞的疏水性活性物质,然后使用纯乙醇破坏脂质体的结构以释放用于浓度测量的疏水性活性物质来对其进行测量。具体地,最终制备的脂质体的含水分散体的一个等分试样(0.2ml)用适当含水介质如500ml PBS进行透析,以完全除去任何未填塞的疏水性活性物质。在透析后,移出在透析袋中的剩余内容物并转移到分开的容器中,并将乙醇加到该容器中至最终体积为25ml。然后通过HPLC测定填塞的疏水性活性物质(CS)在乙醇中的浓度,并且因此计算疏水性活性物质的量。
CU代表初始加入有机溶剂中以制备脂质体的含水分散体的疏水性活性物质的总量。它包括填塞到脂质体中的疏水性活性物质的量和以脂质体分散体水相中未填塞的化学物质表示的活性物质的量。具体地,将制备的脂质体的含水分散体的相同等分试样(0.2ml)转移到分开的容器中,并将乙醇加到该容器中至最终体积为25ml。然后通过HPLC测定疏水性活性物质(CU)总量的浓度,并且因此计算疏水性活性物质的量。
在HPLC测量中,购自Shimadza Corporation,Kyoto,Japan的代码为LC-2010AHT的HPLC设备可与购自Thermo Fisher Scientific的色谱柱Hypersil ODS(250mm*4.6mm)一起使用,并且移动相为甲醇:水=95:5,色谱中的pH用H3PO4调节至3.5。虽然使用HPLC作为测量疏水性活性物质浓度的合适方法,也可使用其它浓度测量方法。
渗透效率测量---扩散池测试
渗透效率用于测量透过皮肤的某些表面区域并到达真皮层的疏水性活性物质的量。Franz扩散池系统也称为Franz-扩散室,常在工业中用于测量化学物质的皮肤渗透效率。
Franz-扩散室包括一个在上端的供体隔室和一个在下端的受体隔室,其中两个隔室的内部空间通过一个阻隔分开。受体隔室通常具有一个取样端口,便于实时监测并分析通过阻隔流入受体隔室的样品。阻隔可为天然皮肤制剂或人工皮肤构造(ASC)。ASC可由不同的细胞类型培养获得并包括真皮和表皮等同物。
在测试期间,将样品载入供体隔室并设置其通过阻隔流向受体隔室。受体隔室填充有15%v/v的乙醇-PBS溶液。可从受体隔室的取样端口取出样品用于测量。计算到达受体隔室的皮肤活性物质的量除以阻隔表面积,作为渗透效率。
在皮层内的疏水性活性物质的残留量
这种残留量用于测量残留在皮肤中的活性物质的总量(在其渗透的皮肤的整个深度上)。在上述渗透测试结束时,当在供体隔室中的所有样品已经流过阻隔时,移出阻隔并用纯水冲洗其表面五次,随后放回Franz-扩散室。然后受体隔室填充50%v/v的乙醇-PBS并且Franz扩散室再静置12小时以溶解所有保留在阻隔不同层内的GA。然后从受体隔室的取样端口取出样品并且可通过HPLC测定样品中的活性物质浓度。
使用方法
可将本发明的脂质体掺入包括化妆品组合物和药物组合物的个人护理组合物中,用于改善疏水性活性物质的透皮递送目的。化妆品组合物可为霜膏、乳液、凝胶、洗剂、爽肤水、以及它们的组合的形式。
实例
实例1-4涉及本发明的脂质体的含水分散体。实例1涉及正常脂质体,实例2还涉及加入胆固醇的脂质体,实例3和4还涉及加入弹性增强剂的脂质体。比较例1-2示出包含疏水性活性物质的那些组合物,但是不在本发明的范围内。具体地,比较例1涉及缺乏亲水性辅助剂的脂质体,并且比较例2示出与脂质体递送相比较作为疏水性活性物质递送载体的水包油型霜膏。
给出的这些实例仅仅是说明性的,不可理解为是对本发明的限制,因为在不脱离本发明实质和范围的条件下可作出许多变型。除非下文另外说明,此处适用的成分均以化学名或CTFA名来识别。
表1
1.氢化大豆胆碱磷酸(HSPC),可以商品名Phopholipon80H从Shanghai ToshisunEnterprises Co.Ltd.商购获得
2.聚氧乙烯(10)胆固醇醚购自Nihon Emulsion Co.Ltd.
3.甘草次酸,购自Xinjiang Tianshan Pharmaceutical Ltd.
4.L-赖氨酸,生物技术级,购自Solarbio Science&Technology Co.,Ltd.
实例1的脂质体通过首先在70℃下,在清洁圆底烧瓶中将1.2克氢化大豆胆碱磷酸(HSPC)、0.288g维生素E乙酸酯和120mg甘草次酸(GA)溶解在20ml乙醇中形成预混物来制备。然后通过旋转真空蒸发除去乙醇,并且在烧瓶底部形成脂质膜。然后用包含82mg溶解L-赖氨酸的40g0.005M,pH7.0的PBS溶液水合脂质膜,同时进行磁力搅拌,持续30分钟。GA:赖氨酸摩尔比=1:2。然后水合溶液通过匀化器进行3次5000psi的高压均化以获得均一化的脂质体的含水分散体,所述匀化器以商品名Emulsiflex C5购自Avestin,Canada。所得样品在室温下储存。
实例2-4的三种脂质体的制备不同于实例1的脂质体制备,不同之处在于还分别加入了219.9mg的胆固醇,219.9mg的Tween-80,110g Tween-80和110g具有式C27H45O(CH2CH2O)10H(也称为CS10)的聚氧乙烯胆固醇醚的混合物到乙醇预混物中。
比较例1的脂质体的制备不同于实例3的脂质体的制备,不同之处在于水合介质缺乏赖氨酸,并且加入的甘草次酸含量略低。
比较例2的组合物的制备可通过制备水包油型乳液的常规方法进行。实例2的霜膏包含0.3%的甘草次酸和99.7%的水包油型霜膏基料,所述霜膏基料包含1.4%的脂肪醇(十六烷基醇、硬脂醇、二十二醇和十六/十八醇的混合物),2%的硅油(聚二甲基硅氧烷和聚二甲基硅氧烷醇),0.25%的硅氧烷粉末(聚甲基倍半硅氧烷)和2%Sepigel305,一同添加水与其它成分至总量为100%。
测量和功效
1.填塞率测量
本发明实例1-4的脂质体和比较例1的脂质体的填塞率根据上文测量方法部分描述的测量方法进行测量。认为在比较例2的霜膏中的甘草次酸填塞率是100%,因为它完全掺入了霜膏的油相。
从上表1中可以看出本发明实例1-4的包含赖氨酸的脂质体具有比比较例1的不包含赖氨酸的脂质体明显更高的填塞率。填塞率数据也在图1中示出。
2.渗透效率测量
在把样品加入供体隔室之前将Franz扩散室用纯水平衡1小时。适当表面积的大鼠皮肤制剂用作阻隔置于受体和供体隔室之间,所述适当表面积对应于Franz扩散室有效扩散面积。具有0.66cm2的有效扩散面积和2.5ml的受体槽体积的Franz扩散室用于该测量。
将200μl脂质体的含水分散体制剂的等分试样转移到供体隔室中,并且用未封闭的供体隔室进行该实验。受体隔室填充有15%v/v的乙醇-PBS(pH=7.4)溶液。在受体槽中的乙醇-PBS溶液用磁力混合器以280rpm的速度在37±0.2℃下持续匀化。在1、3、5、8小时后,从受体隔室取出2.5ml样品并通过HPLC测定甘草次酸浓度,并且通过乘以样品体积相应地计算渗透的GC量。
表2GA渗透效率比较
从表2中可看出,与通过比较例2的水包油型霜膏的递送相比,当经由本发明实例3的脂质体递送时,透过大鼠皮肤的甘草次酸的量显著增加。这个GA渗透效率数据也在图2中示出。
3.残留量测量
在渗透测试结束时,当供体隔室中的所有样品透过大鼠皮肤时,取出所述皮肤,按照前文测量方法部分描述的方法进行残留量测量。
表3GA残留量比较
从表3中可看出,与经由比较例2的水包油型霜膏的甘草次酸递送相比,经由实例3的脂质体的递送显著改善了所有大鼠皮层中积聚的甘草次酸的量。这一残留量测量数据也在图3中示出。
本文所公开的量纲和值不旨在被理解为严格地限于所述的精确值。相反,除非另外指明,每个这样的量纲旨在表示所述值以及围绕该值功能上等同的范围。例如,所公开的量纲“40mm”旨在表示“约40mm”。
除非明确地不包括在内或换句话讲限制,本文所引用的每篇文献,包括任何交叉引用的或相关的专利或专利申请,均特此以引用方式全文并入本文。任何文献的引用不是对其作为本文所公开的或受权利要求书保护的任何发明的现有技术,或者其单独地或者与任何其它参考文献的任何组合,或者参考、提出、建议或公开任何此类发明的认可。此外,当本发明中术语的任何含义或定义与以引用方式并入的文件中术语的任何含义或定义矛盾时,应当服从在本发明中赋予该术语的含义或定义。
尽管已用具体实施例来说明和描述了本发明,但是对那些本领域的技术人员显而易见的是,在不背离本发明的精神和范围的情况下可作出许多其它的更改和修改。因此,随附权利要求书旨在涵盖本发明范围内的所有这些改变和变型。
Claims (18)
1.脂质体,包含:
a)磷脂;
b)包含羧酸根基团的疏水性活性物质;以及
c)组分,其选自:包含带正电基团的亲水性辅助剂,所述疏水性活性物质与所述亲水性辅助剂的复合物,以及它们的组合,
其中所述疏水性活性物质选自甘草次酸、甘草亭酸硬脂酸酯、甘草酸、十一碳烯酰基苯丙氨酸、视黄酸、抗坏血酸四异棕榈酸酯、以及它们的组合,
其中所述亲水性辅助剂为碱性氨基酸,所述碱性氨基酸选自赖氨酸、精氨酸、组氨酸、以及它们的组合;
所示脂质体通过以下方法制备,所述方法包括以下步骤:
a)通过将磷脂和包含羧酸根基团的疏水性活性物质溶解在有机溶剂中形成预混物;
b)从所述预混物中蒸发掉所述有机溶剂以形成磷脂膜;
c)用包含具有带正电基团的亲水性辅助剂的水合介质使所述膜水合,以及
d)均化所述水合介质以形成脂质体的含水分散体。
2.根据权利要求1所述的脂质体,其中所述疏水性活性物质的含量为以所述磷脂的重量计1重量%至20重量%。
3.根据权利要求1所述的脂质体,其中所述亲水性辅助剂的含量为以所述磷脂的重量计1重量%至20重量%。
4.根据权利要求1所述的脂质体,其中所述疏水性活性物质与所述亲水性辅助剂的摩尔比为1:10至10:1。
5.根据权利要求1所述的脂质体,其中所述磷脂为氢化的磷脂。
6.根据权利要求1所述的脂质体,还包含弹性增强剂,所述弹性增强剂选自非离子表面活性剂。
7.根据权利要求1所述的脂质体,还包含弹性增强剂,所述弹性增强剂选自聚氧乙烯胆固醇醚。
8.根据权利要求6所述的脂质体,其中所述非离子表面活性剂为聚山梨醇酯80或脱水山梨糖醇单油酸酯。
9.根据权利要求7所述的脂质体,其中所述聚氧乙烯胆固醇醚为C27H45O(CH2CH2O)nH,其中n为5至15。
10.根据权利要求1所述的脂质体,还包含抗氧化剂,所述抗氧化剂选自维生素E、维生素E酯、维生素C、维生素C酯、以及它们的组合。
11.脂质体的含水分散体,包含权利要求1-5中任一项所述的脂质体,其中所述磷脂的含量为以所述含水分散体的重量计1重量%至20重量%。
12.脂质体的含水分散体,包含权利要求6-9中任一项所述的脂质体,其中所述磷脂的含量为以所述含水分散体的重量计1重量%至20重量%。
13.脂质体的含水分散体,包含权利要求10所述的脂质体,其中所述磷脂的含量为以所述含水分散体的重量计1重量%至20重量%。
14.根据权利要求12所述的脂质体的含水分散体,其中所述弹性增强剂的含量为以所述含水分散体的重量计0.01重量%至10重量%。
15.根据权利要求13所述的脂质体的含水分散体,其中所述抗氧化剂的含量为以所述含水分散体的重量计0.01重量%至5重量%。
16.个人护理组合物,包含权利要求1-10中任一项所述的脂质体,所述个人护理组合物为选自下列的形式:霜膏、乳液、凝胶、洗剂、爽肤水、以及它们的组合。
17.个人护理组合物,所述个人护理组合物通过使用权利要求11-15中任一项所述的脂质体的含水分散体而制备,所述个人护理组合物为选自下列的形式:霜膏、乳液、凝胶、洗剂、爽肤水、以及它们的组合。
18.制备脂质体的方法,包括以下步骤:
a)通过将磷脂和包含羧酸根基团的疏水性活性物质溶解在有机溶剂中形成预混物;
b)从所述预混物中蒸发掉所述有机溶剂以形成磷脂膜;
c)用包含具有带正电基团的亲水性辅助剂的水合介质使所述膜水合,以及
d)均化所述水合介质以形成脂质体的含水分散体;
其中所述疏水性活性物质选自甘草次酸、甘草亭酸硬脂酸酯、甘草酸、十一碳烯酰基苯丙氨酸、视黄酸、抗坏血酸四异棕榈酸酯、以及它们的组合,
其中所述亲水性辅助剂为碱性氨基酸,所述碱性氨基酸选自赖氨酸、精氨酸、组氨酸、以及它们的组合。
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