CN109890347A - 延迟释放递送体系和方法 - Google Patents
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Abstract
本发明公开了一种延迟释放递送体系,该延迟释放递送体系包括亲水性芯颗粒,该亲水性芯颗粒具有表面孔并且包含液体。所述颗粒被包封在聚合物中,该聚合物具有疏水性主链和亲水性侧基。邻近亲水性侧基的表面孔中的至少一些表面孔在有水的情况下被阻塞并且在没有水的情况下被消除阻塞。经处理的颗粒包含液体,其中液体与多孔芯颗粒的重量比为至少400:1。
Description
技术领域
本发明涉及可充当用于芳香剂或皮肤有益成分、头皮有益成分和头发有益成分的持续递送体系的颗粒、用于制备这些颗粒的方法,以及包含这些颗粒的组合物。更具体地,颗粒吸收芳香剂或活性物质并且在较长时间内逐渐释放这些芳香剂或活性物质。
背景技术
芳香剂用于各种产品中,以增强消费者在使用这些产品时的乐趣。人们长期以来一直认识到生产这类产品的愿望:将它们施用于皮肤、头皮或头发后,可长久保持其香味。尽管在这方面做了许多努力,但是大多数用于皮肤、头皮和头发的商业产品最初具有强烈的令人愉快的气味,但令人失望的是,在施用后几分钟内往往会失去其气味。解决该问题的尝试包括使用浸渍有芳香剂的无机载体掺入产品中。EP 0332259A公开了通过将香料吸附在二氧化硅上而制备的香料颗粒。美国5,336,665公开了自由流动的疏水性多孔无机疏水性载体颗粒,诸如硅铝酸盐,这些颗粒具有一定的孔体积和孔直径并且具有吸附在这些颗粒中的香料。美国5,246,919公开了一种芳香材料,其由氯化钠颗粒料聚集体组成并且具有吸收在颗粒料之间的孔中的芳香油。
已作出努力来增加芳香剂保留在身体角质表面上的时间量而不增加芳香剂负荷,诸如通过使用涂层和微胶囊体系。美国4,020,156描述了一种芳香小珠组合物,其由具有包含芳香剂的粘附表面涂层的多个颗粒状尿素小珠组成。美国2006/0153889描述了一种用于颗粒的不连续表面涂层,该不连续表面涂层允许活性物质从芯颗粒上的下层沉积物中受控地释放。
微胶囊技术在本领域中是公知的并且通常涉及包封需要保护的芯材料,直到在保护性覆盖物中使用时为止。一般来讲,高粘度流体将从载体中更缓慢地分散,这倾向于延长芳香剂的持续时间,而较低粘度流体将因为较高的蒸发率而增强香味的强度。延时释放微胶囊以受控速率释放其芯材料。结果是,被包封材料具有较长的有效寿命,因为其不会立即从保护性微胶囊中释放。美国7,294,612描述了一种聚合物包封的液体芳香剂,该液体芳香剂经阳离子聚合物进一步处理以改善沉积。如美国6,245,733中所述,熔融微球的预玻璃附聚物使用微毛细管作用快速吸收油基或醇基液体,使预玻璃附聚物的重量增加一倍以上。美国7,622,132描述了一种由热软化材料的易碎胶囊包封的化妆品材料,该热软化材料在室温下是固体,但当组合物在皮肤表面上摩擦时会破裂并在施用于皮肤时熔化。
尽管有上述专利,仍然持续需要这样的芳香剂产品,它们在延长的时间段内表现出香味持续释放到皮肤、头皮和头发上的延长持续时间。
发明内容
根据本发明的一个方面,提供了包括至少一种经处理的颗粒的延迟释放递送体系。
在本发明的该方面的一个实施方案中,经处理的颗粒包括亲水性芯颗粒,该亲水性芯颗粒具有表面孔和包含在其中的液体。亲水性芯颗粒进一步由聚合物包封,该聚合物具有疏水性主链和多个亲水性侧基。邻近亲水性侧基的表面孔中的至少一些表面孔在有水的情况下被阻塞并且在没有水的情况下被消除阻塞。
在本发明的该方面的另一个实施方案中,经处理的颗粒包括多孔芯颗粒,该多孔芯颗粒具有多孔表面和吸收在多孔芯颗粒中的液体。液体与多孔芯颗粒的重量比为至少约400:1,诸如从约400:1至约800:1。
根据本发明的另一个方面,提供了一种用于制备延迟释放递送体系的方法。
在本发明的该方面的一个实施方案中,制备延迟释放递送体系的方法包括以下步骤:
(a)提供至少一种亲水性芯颗粒,该至少一种亲水性芯颗粒具有表面孔且具有吸收在其中的液体;
(b)使(a)的颗粒与液体聚合物接触足够的时间,以便用液体聚合物包封所述至少一种颗粒,以形成至少一种经处理的颗粒,其中液体聚合物具有疏水性主链和多个亲水性侧链,并且其中邻近亲水性侧链的亲水性芯颗粒上的至少一些表面孔在有水的情况下被阻塞并且在没有水的情况下被消除阻塞;以及
(c)将至少一种经处理的颗粒分散在含水的美容上可接受的媒介中。
根据本发明的该方面的另一个实施方案,用于制备延迟释放递送体系的方法包括以下步骤:
(a)提供多孔芯颗粒;以及
(b)使多孔芯颗粒与液体在足以使该液体被吸收到芯颗粒中的条件下接触,其中该液体与多孔芯颗粒的重量比为至少约400:1。
具体实施方式
本发明的延迟释放递送体系包括多孔颗粒,该多孔颗粒具有吸收在其中的液体。
延迟释放递送体系包括至少一种经处理的颗粒,该至少一种经处理的颗粒包括亲水性芯颗粒,该亲水性芯颗粒具有用聚合物包封的表面孔。该聚合物具有疏水性主链和多个亲水性侧基。该聚合物使经处理的颗粒的表面上的孔阻塞,例外的是颗粒表面上邻近聚合物上亲水性侧基的至少一些孔在有水的情况下被阻塞并且在没有水的情况下被消除阻塞。在含水环境的存在下,经处理的颗粒中包含的液体被保留在颗粒中,因为水分子被吸引到亲水性侧基上并且阻塞邻近侧基的至少一些表面孔。
当在储存期间悬浮在含水碱中或在含水产品中时,经处理的颗粒保持完整性。例如,当被擦到皮肤上时,随着产品中的水蒸发,阻塞聚合物上亲水性侧基附近的孔的水分子从孔中拉开,使得经处理的颗粒中所包含的液体以缓慢和持续的方式逐渐通过孔释放。
任何能够吸收液体的亲水性多孔芯颗粒都可用于制备该延迟释放递送体系。通常,此类颗粒由无机材料形成,该无机材料包括但不限于二氧化硅、甲硅烷基化二氧化硅和硅酸钙。由这些无机材料形成的微球,尤其是亲水性微球,优选用于本发明的延迟释放递送体系中。用于本发明的亲水性微球可以是天然的或合成的,并且具有约100nm至约50μm的平均粒度。尤其优选的是对吸油具有高亲和力的微球。一种此类微球由硅酸钙形成,可作为购自Tomita Pharmaceutical Co.,Ltd.,这种微球具有约29μM的粒度。该合成材料具有花瓣状晶体结构,具有明显的深度、大的孔径和体积,以及优异的液体吸收性。与其他无机材料相比,硅酸钙吸收其重量的至少五倍的油和水。100g的硅酸钙粉末吸收650g的油。由二氧化硅形成的微球,诸如二氧化硅壳也是有用的。这些微球可得自KOBO,具有约3μM的粒径,并且每100g二氧化硅粉末吸收400-600g油。还可用的是由甲硅烷基化二氧化硅、热解法二氧化硅形成的微球,它可作为CAB-O-SIL TS-530购自Cabot。用六甲基二硅氮烷处理二氧化硅。该处理用三甲基甲硅烷基取代许多表面羟基,使得二氧化硅极其疏水。
可用于本发明的延迟递送体系的聚合物具有疏水性主链和亲水性侧基或侧链。该聚合物的主链足够疏水,以良好地粘附到液体填充的多孔颗粒的表面上。亲水性侧链的行为类似于刷子的刷毛。刷毛足够长并且沿着聚合物主链适当地间隔开,以使得侧链不仅能够吸引水,而且能够捕集和保持水。尤其优选的聚合物是具有硅氧烷主链的那些聚合物。硅氧烷很好地粘附到多孔颗粒上,并且可通过添加亲水性侧链进行改性。一种这样的优选聚合物具有含聚甘油侧链的硅氧烷主链。该聚合物的硅氧烷主链或疏水性侧粘附到多孔颗粒表面,锚定在孔中。该聚合物尤其很好地粘附到填充有含油液体的亲水性多孔颗粒上。孔中的油使得亲水性颗粒的行为类似于疏水性颗粒,以便使该聚合物很好地粘附到颗粒表面上。聚甘油侧链形成该聚合物的亲水性侧并且不附接到微球表面。当将本发明的聚合物涂覆的经处理的颗粒分散在含水碱中时,碱中的水分子被吸引到侧链。水分子氢键合到侧链并围绕每个颗粒。水分子在侧链从聚合物主链延伸的点处阻塞聚合物中的空间。侧链的数目越大,与经处理的颗粒相关联的水就越多。当包含经处理的颗粒的含水产品被擦到皮肤上时,水从包含经处理的颗粒的产品中蒸发。与经处理的颗粒相关联的水是最后蒸发的。一旦那些水分子不再可用于阻塞硅氧烷主链中的孔(侧链所在的位置),那些区域中先前阻塞的孔就暴露出来,并且芳香剂开始从经处理的颗粒中排出。
环境湿度水平可影响水从包含液体填充的经处理的颗粒的产品中的蒸发。环境湿度越高,由于水蒸发越慢,液体释放越慢。
经处理的颗粒中夹带的液体越多,液体例如,包含芳香剂油的液体被释放所需的时间越长,并且香味在皮肤上的持续时间越久。液体的扩散率还将影响释放时间。
让经处理的颗粒在不相容的媒介中悬浮可进一步延迟夹带在颗粒孔中的液体的释放。例如,包含芳香剂油的经处理的颗粒可以分散在含水碱中用于储存,或者分散在含水产品中。
预期影响液体例如芳香剂油的受控释放以及由此芳香剂在皮肤上的持续性的另一个因素包括多孔颗粒上的聚合物涂层的厚度。由于聚合物涂层是疏水性的,一旦水从皮肤产品蒸发,皮肤上的油将缓慢溶解经处理的颗粒上的涂层,从而允许液体逸出。随着聚合物厚度的增加,夹带的液体的释放的持续时间将越长。
类似地,掺入有经处理的颗粒的产品中的油相的量也将对包含的液体的延时释放产生影响。一旦水从产品中蒸发,产品中的油将开始逐渐溶解疏水性聚合物涂层并导致液体从颗粒中持续释放。产品中油相的量越小,液体的释放就越慢。
对于包含液体的经处理的颗粒,它们在包含这些颗粒的产品中的量也会影响施用该产品的皮肤上芳香剂的持续时间。
任何能够被吸收到亲水性芯颗粒中的液体都可用于制备该延迟释放递送体系。该液体可为水基的、油基的、水包油乳液、水包硅氧烷乳液、油包水乳液、硅氧烷包水乳液或多重乳液。优选地,该液体将选自包含以下项的那些液体:芳香剂油、皮肤有益活性物质、头皮有益活性物质或头发有益活性物质,以及它们的组合。
该延迟释放递送体系可通过以下步骤制备:
(a)提供至少一种亲水性芯颗粒,该亲水性芯颗粒具有表面孔和吸收在其中的液体;
(b)使(a)的颗粒与液体聚合物在能够充分用液体聚合物包封所述至少一种颗粒的条件下接触,以形成至少一种经处理的颗粒,其中液体聚合物具有疏水性主链和多个亲水性侧链,并且其中邻近亲水性侧链的亲水性芯颗粒上的至少一些表面孔在有水的情况下被阻塞并且在没有水的情况下被消除阻塞;以及
(c)将至少一种经处理的颗粒分散在含水的美容上可接受的媒介中。
该亲水性芯颗粒可以是能够将液体吸收在其中的任何亲水性多孔颗粒,如上所述。
任何能够被吸收到亲水性芯颗粒中的液体都可用于制备该延迟释放递送体系,如上所述。液体可通过本领域中已知的任何合适的方法被吸收到至少一种芯颗粒中。
使液体填充的经处理的颗粒与聚合物接触的步骤可以使用本领域技术人员已知的用于将涂层施加到颗粒上的任何合适的方法进行,包括但不限于混合、喷涂,和超声处理中的至少一者。
用聚合物包封液体填充的芯颗粒的优选方法是使用超声处理。用透射电子显微镜(TEM)测量液体填充的颗粒的平均尺寸(例如,填充有包含芳香剂油的液体的3μm二氧化硅颗粒)。在容器中混合70%水、28%液体填充颗粒和2%液体聚合物以形成浆液。然后使用购自Sonicor Instrument Co.的超声波探头将该浆液在中等强度、20kHz、25℃下超声处理30分钟,得到浓稠的胶态悬浮液。将该悬浮液在1000rpm下离心15分钟以沉淀颗粒并去除未附接的聚合物材料。用去离子水洗涤所得混合物,并且重复洗涤步骤三次。在超声处理后再次使用TEM测量经处理的颗粒上的聚合物涂层的均匀度和厚度。聚合物涂层的厚度将是允许聚合物锚定到孔中的量,同时避免过厚的涂层,过厚的涂层可能预期会不利地影响液体的释放。聚合物厚度将优选地在约10nm至约30nm的范围内。预计小于约10nm的涂层将不会均匀地涂覆多孔颗粒,而厚度大于约30nm的涂层可预期基本上防止液体从经处理的多孔颗粒中释放出来。为了防止经处理的颗粒脱水(这将活化液体的释放),随后将经处理的颗粒浸没在约70重量%的水中。
适用于本发明的延迟释放递送体系的聚合物包括但不限于上文所讨论的那些中的任一种。
在本发明的另一个实施方案中,延迟递送体系包括至少一种经处理的颗粒,该至少一种经处理的颗粒包括芯颗粒,该芯颗粒具有多孔表面和吸收在芯颗粒中的液体。该液体的重量与芯颗粒的重量的比率为至少约400:1。更优选地,该比率介于约400:1和约800:1之间,包括其中的任何比率,包括401:1至799:1,以及其中的任何范围。
任何能够吸收液体的多孔颗粒均可用于制备该延迟释放递送体系,如上文所述。
该延迟释放递送体系可通过以下步骤制备:
(a)提供多孔芯颗粒;以及
(b)使多孔芯颗粒与液体在足以使该液体被吸收到多孔芯颗粒中的条件下接触,其中该液体与多孔芯颗粒的重量比为至少约400:1。
可用于制备延迟释放递送体系的该方法中的多孔芯颗粒可包括能够将液体吸收在其中的任何多孔颗粒。可用的多孔颗粒可包括但不限于上文所述的亲水性颗粒。
通过使芯颗粒与液体在至少100psi的压力下接触至少30分钟,使液体被吸收到芯颗粒中。更优选地,使用的压力在大于100psi至约1000psi的范围内,包括其间的任何值,包括101至999psi和该范围内的任何整数,诸如300psi、500psi、700psi等,接触时间可以是约30分钟至最多约2小时的任何时间,诸如约1小时。接触步骤可重复至少一次,例如一至三次。高压将颗粒中的孔扩大,使得颗粒能够容纳更多的液体,并且还将液体推进到孔中。达到所需液体吸收量所需的压力和时间与液体密度成比例地增加。一般来讲,将多孔颗粒和待吸收的液体以约1:5至约1:10的多孔颗粒与液体之比混合,并且将所得浆液转移到高压槽中。然后使浆液经受高压至少30分钟,并且至多约2小时。
该方法还可包括将经处理的颗粒包封于如上文所述的聚合物涂层中的步骤。
可通过使液体的表面张力与多孔芯颗粒(例如,微球)的表面张力相容来促进多孔颗粒对液体的吸收。液体的表面张力可在约30-72dyne/cm的范围内。例如,疏水性液体,诸如包含芳香剂油的液体,可具有范围在约30-45dyne/cm的表面张力。可将稀释剂组合在内以改变芳香剂油的表面张力。包含疏水性液体诸如芳香剂油的多孔颗粒通常具有在约40-70dyne/cm的范围内的表面张力。在某些实施方案中,表面张力被改性,其中将具有疏水性主链和亲水性侧链或侧基的聚合物涂覆到包含液体的多孔颗粒上。在这种情况下,涂覆的颗粒的表面张力将在约60-72dyne/cm的范围内,以确保经处理的颗粒可分散于产品的水相中。如上所述,当水从含水产品中蒸发时,将活化包含在多孔颗粒中的液体的释放。表面张力可通过本领域已知的用于此目的的任何方法测量。可用于测量液体表面张力的仪器的示例是购自Krüss的表面张力计K100。
一种确定特定液体(例如包含芳香剂油的液体)被吸收到多孔颗粒中所需的压力和时间的方法使用了共焦激光扫描显微镜法(CLSM)。通过将芳香剂油与荧光染料例如尼罗红混合,将包含染料的油掺入稀释剂中,并且在不同压力和时间的条件下将液体与芯颗粒混合来制备样品。将每个制备的包含液体的微球的样品放置在微型载片上并在共焦显微镜下检查。发射/反射光由光电倍增器转换成电信号并且显示在计算机监视器屏幕上。该方法允许测量表面积和在数学上计算芳香剂油所占的体积。
任何能够被吸收到芯颗粒中的液体都可用于制备延迟释放递送体系,如上所述。在稀释剂中包含芳香剂或活性物质以便被芯颗粒吸收的液体可以是亲水性或疏水性的。如上所述,为了实现液体在多孔颗粒中的最佳载量,液体和芯颗粒的表面张力应当是相容的。例如,为了将芳香剂油的表面张力改性为与芯颗粒的表面张力更相容,芳香剂油可与一种或多种稀释剂混合。
适用于本发明的芳香剂无限制地包括芳香剂组合物的任何芳香剂,包括芳香剂油、植物提取物、合成芳香剂或它们的混合物,这些芳香剂能够与本发明的延迟释放递送体系相容并且能够被包封在该体系中,并且也与所采用的包封工艺相容。合适的芳香剂包括但不限于来源于水果、花和草本植物,以及油(包括精油)的那些芳香剂。合适的芳香剂来源可见于Hilda Butler所著的Poucher’s Perfumes Cosmetics and Soaps 2000年第10版。
经处理的颗粒,无论是否被包封在聚合物中,均可悬浮在美容上可接受的媒介中。此类美容上可接受的媒介可为水基的、油基的、水包油乳液、水包硅氧烷乳液、油包水乳液、硅氧烷包水乳液或多重乳液。就包封在聚合物中的经处理的颗粒而言,该媒介是含水的。该媒介可包括美容上进一步可接受的皮肤有益成分、头皮有益成分或头发有益成分。
Claims (10)
1.一种延迟释放递送体系,所述延迟释放递送体系包括至少一种经处理的颗粒,所述经处理的颗粒包括亲水性芯颗粒,所述亲水性芯颗粒具有表面孔和包含在其中的液体,所述亲水性芯颗粒进一步被聚合物包封,所述聚合物具有疏水性主链和多个亲水侧基,其中邻近所述亲水性侧基的所述表面孔中的至少一些表面孔在有水的情况下被阻塞并且在没有水的情况下被消除阻塞。
2.根据权利要求1所述的延迟释放递送体系,其中所述聚合物包含硅氧烷主链。
3.根据权利要求2所述的延迟释放递送体系,其中所述聚合物用聚甘油侧基改性。
4.根据权利要求1所述的延迟释放递送体系,其中所述液体为水基的、油基的、水包油乳液、水包硅氧烷乳液、油包水乳液、硅氧烷包水乳液或多重乳液。
5.根据权利要求1所述的延迟释放递送体系,其中所述液体包含芳香剂油、皮肤有益活性物质、头皮有益活性物质、头发有益活性物质或它们的组合。
6.根据权利要求1所述的延迟释放递送体系,其中所述液体和所述经处理的颗粒具有相容的表面张力。
7.根据权利要求1所述的延迟释放递送体系,其中所述亲水性芯颗粒为平均粒度介于约100nm至约50μm的微球。
8.根据权利要求7所述的延迟释放递送体系,其中所述亲水性芯颗粒具有从所述颗粒的所述表面延伸穿过所述芯的一系列微孔。
9.一种化妆品组合物,所述化妆品组合物包括在含水的美容上可接受的媒介中的根据权利要求1所述的延迟释放递送体系。
10.根据权利要求9所述的化妆品组合物,包含至少一种另外的皮肤有益成分、头皮有益成分或头发有益成分。
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JP6902097B2 (ja) | 2021-07-14 |
US20180110687A1 (en) | 2018-04-26 |
JP2019533686A (ja) | 2019-11-21 |
EP3532010B1 (en) | 2021-01-06 |
US10363205B2 (en) | 2019-07-30 |
CA3041789A1 (en) | 2018-05-03 |
WO2018080678A1 (en) | 2018-05-03 |
AU2017352302A1 (en) | 2019-05-30 |
ES2859726T3 (es) | 2021-10-04 |
CN109890347B (zh) | 2023-10-31 |
KR20190055846A (ko) | 2019-05-23 |
KR102270658B1 (ko) | 2021-07-01 |
EP3532010A1 (en) | 2019-09-04 |
EP3532010A4 (en) | 2019-09-04 |
AU2017352302B2 (en) | 2020-09-10 |
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