CN111686017A - 一种祛痘纳米脂质载体及制备方法 - Google Patents
一种祛痘纳米脂质载体及制备方法 Download PDFInfo
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- CN111686017A CN111686017A CN202010391244.2A CN202010391244A CN111686017A CN 111686017 A CN111686017 A CN 111686017A CN 202010391244 A CN202010391244 A CN 202010391244A CN 111686017 A CN111686017 A CN 111686017A
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Abstract
本发明涉及化妆品技术领域，尤其涉及一种祛痘纳米脂质载体及制备方法。这种祛痘纳米脂质载体按照质量份，包括祛痘活性物1‑10份、碱1‑10份、固体脂质5‑30份、液体脂质5‑20份、油包水型乳化剂1‑10份以及水包油型乳化剂1‑10份。本申请将祛痘活性物负载在三相分散体系的纳米脂质载体上，能很好地解决稳定性差、刺激性强的水溶性活性物的包覆问题，使其有效发挥祛痘功效。且制备仅需要油脂、去离子水及乳化剂，仅需要加热及均质即可以完成制备，其产物在安全性、可操作性上具有一定的优势。
Description
技术领域
本发明涉及化妆品技术领域，尤其涉及一种祛痘纳米脂质载体及制备方法。
背景技术
青春痘，又名痤疮，是一种好发于颜面、胸、背部的毛囊及皮脂腺的慢性炎症性皮肤病。其典型皮损表现为粉剌、丘瘆、脓痕、结节及囊肿。青春痘的发生与皮脂分泌过多、毛囊皮脂腺导管堵塞、细菌感染和炎症反应等主要因素密切相关。常见的，进入青春期后人体内雄激素特别是睾酮的水平迅速升高，促进皮脂腺发育并产生大量皮脂；同时毛囊皮脂腺导管的角化异常造成导管堵塞，皮脂排出障碍，形成角质栓；毛囊中多种微生物尤其是痤疮丙酸杆菌大量繁殖，痤疮丙酸杆菌产生的脂酶分解皮脂生成游离脂肪酸；同时趋化炎症细胞和介质，最终诱导并加重炎症反应。青春痘严重影响人的容貌和自信，对人们的工作、生活产生消极影响，因此祛痘是化妆品的研究焦点之一。
祛痘最有效的机理是：首先松动角栓，然后使得厌氧菌痤疮杆菌接触氧气使其无法生长。
祛痘常用的活性物质有水杨酸，其分子式为C7H6O3，是植物柳树皮提取物，是一种天然的消炎药。水杨酸可以祛角质、杀菌、消炎，因而非常适合治疗毛孔堵塞引起的青春痘，国际主流祛痘产品都是含水杨酸的，浓度通常是0.5~2%。但是水杨酸对皮肤和粘膜的刺激性较大，会与机体组织中的蛋白质发生反应，所以有腐蚀作用。且水杨酸仅能够松动角栓，不能够导入氧气，祛痘效果一般。
而另一种祛痘常用活性物质是BPO过氧化苯甲酰，过氧化苯甲酰有大量氧气，直接涂抹就能对着痤疮杆菌发射氧气。但是其刺激性较大、具有易过敏的问题。
纳米结构脂质载体（NLC）是在固体纳米脂质粒（SLN）基础上发展起来的新型载体，能够克服SLN的载药能力有限、药物储存过程中易泄漏、以水分散体形式存在时分散液中水分含量过高等缺陷。NLC在SLN的基础上将固态油脂替换为固态油脂和液态油脂的混合物，使得其具有更加不规则的缺陷型结构，从而产生更多的空间来容纳更多的活性物质，有效的提高了其包覆率，从而缓慢释放出活性物质，降低刺激性。
发明内容
本发明要解决上述问题，提供一种祛痘纳米脂质载体及制备方法。
本发明解决问题的技术方案是，提供一种祛痘纳米脂质载体，按照质量份，包括祛痘活性物1-10份、碱1-10份、固体脂质5-30份、液体脂质5-20份、油包水型乳化剂1-10份以及水包油型乳化剂1-10份。
优选地，所述祛痘活性物选用水杨酸；按照质量份，还包括壳聚糖1-10份、过氧化尿素0.1-2份、乙酸5-20份、甘油3-8份、环糊精15-20份。
优选地，所述固体脂质包括十八醇、三山嵛酸甘油酯、胆固醇、三肉豆蔻酸甘油酯、棕榈酰硬脂酰甘油酯、三硬脂酸甘油酯、单硬酯酸甘油酯、山嵛醇、月桂酸、甘油硬脂酸酯柠檬酸酯、氢化蓖麻油、棕榈酸、棕榈醇、鲸蜡硬脂醇、脂肪醇和脂肪酸中的一种或几种。
优选地，所述液体脂质包括辛酸癸酸三甘油酯、棕榈酸异丙酯、肉豆蔻酸异丙酯、液体石蜡、棕榈酸异辛酯月桂酸己酯、2-辛基月桂醇、油酸、亚油酸、大豆油和橄榄油中的一种或几种。
优选地，所述油包水型乳化剂包括甘油酸酯枸橼酸酯、蔗糖硬脂酸酯、ABIL EM-90、P135、Span20、Span40、Span60、Span80、Brij 72、Brij 721、A6中的一种或几种。
优选地，所述水包油型乳化剂包括失水山梨醇倍半油酸酯、SS、SSE-20、A25、NovelA、Tween20、Tween40、Tween60、Tween80、K12中的一种或几种。
本发明的另一个目的是提供一种祛痘纳米脂质载体的制备方法，包括以下步骤：
（1）将固体脂质、液体脂质和油包水型乳化剂加热液化混合，得到油相；将祛痘活性物、碱溶于去离子水，得到内水相；将水包油型乳化剂溶于去离子水中，得到外水相；
（2）将内水相加热至油相温度后、在均质的条件下加至油相中，得到粗乳液；降低5-10°粗乳液的温度，并将降温后的粗乳液在均质的条件下加至外水相中，得到乳液；将乳液磁力搅拌后冷却至常温，得到祛痘纳米脂质载体。
优选地，祛痘活性物还需进行前处理，包括以下步骤：
a.将乙酸配置成体积分数为2%的乙酸溶液，将壳聚糖溶于乙酸溶液中得到溶液1；将过氧化尿素溶于甘油中得的溶液2；将溶液2滴加到溶液1中，边加边搅拌，得到溶液3；
b.将水杨酸和环糊精溶于水中得到溶液4，将溶液3缓慢滴加到溶液4中，搅拌5-8h后于2-5℃静置18-24h，然后抽滤，并将得到的滤饼干燥，得到完成前处理的祛痘活性物。
优选地，油相加热温度为60-85℃。
优选地，内水相加入油相中时，均质转速均为15000-25000rpm，均质时间为30-60s。
优选地，粗乳液加入外水相时，均质转速为15000-25000rpm，均质时间为1-5min。
优选地，磁力搅拌转速为500-1200rpm。
本发明的有益效果：
1.将祛痘活性物负载在纳米脂质载体上，这种纳米脂质载体的结构类似于多重乳状液W/O/W，是三相分散体系, 祛痘活性物可以很好的分散于多相组分中，采用生物相容性较好的脂质和乳化剂材料，祛痘活性物则被包埋在粒子内部或吸附在粒子表面，对于包覆水溶性的活性物制备纳米脂质载体具有很好的优越性，能很好地解决稳定性差、刺激性强的水溶性活性物的包覆问题，使其有效发挥祛痘功效。
2.制备仅需要油脂、去离子水及乳化剂，仅需要加热及均质即可以完成制备，其产物在安全性、可操作性上具有一定的优势。
3.采用了水杨酸和过氧化尿素作为祛痘活性物质，通过壳聚糖薄膜包裹过氧化尿素得到包覆体1，再用水杨酸壁材包覆包覆体1得到包覆体2，然后将包覆体2负载在纳米脂质载体上，使其在作用时是循序渐进的——首先通过水杨酸打开角栓，然后通过过氧化尿素释放出氧气，以双重作用来达到优异的祛痘效果。同时，水杨酸和过氧化尿素之间的壳聚糖薄膜层，一方面具有二者的粘附结合作用，另一方面能够改性水杨酸和包覆过氧化尿素，降低两者刺激性。
4.过氧化尿素在分解过程中，还会生成尿素，尿素能够防止干裂，增进角质层的水合作用，从而使皮肤柔软，进一步降低祛痘活性物刺激性造成的皮肤脱皮、发红问题。
附图说明
图1是实施例1中一种祛痘纳米脂质载体的粒径分布图。
图2是实施例2中一种祛痘纳米脂质载体的粒径分布图。
具体实施方式
以下是本发明的具体实施方式，并结合附图，对本发明的技术方案作进一步的描述，但本发明并不限于这些实施例。
实施例1
一种祛痘纳米脂质载体，通过以下方法制备：
（1）按照质量份，准备15份十八醇作为固体脂质，10份棕榈酸异丙酯作为液体脂质，2份Span60作为油包水型乳化剂；2份水杨酸作为祛痘活性物，2份氢氧化钠作为碱；2份Twen60作为水包油型乳化剂。
（2）将固体脂质、液体脂质和油包水型乳化剂在60℃条件下混合均匀形成混合溶液，作为油相。将祛痘活性物、碱溶于去离子水，得到内水相。将水包油型乳化剂溶于去离子水中，得到外水相。
（3）将内水相加热至70℃后、在均质的条件下加至油相中，得到粗乳液，均质转速为20000rpm，均质时间为45s。降低粗乳液的温度至60℃，并将降温后的粗乳液在均质的条件下加至外水相中，得到乳液，均质转速为20000rpm，均质时间为3min。将乳液以800rpm转速磁力搅拌后冷却至常温，得到祛痘纳米脂质载体。
对得到的祛痘纳米脂质载体进行理化性质测定，测定方法如下：
粒径的测定：取祛痘纳米脂质载体0.1m1，用9.9m1去离子水稀释100倍，用激光粒度仪（马尔文仪器）纳米ZS90检测粒径。粒径结果见图1，测得平均粒径为23.8μm，一致性为2.858，表明纳米粒粒径较小且均一。
实施例2
一种祛痘纳米脂质载体，通过以下方法制备：
（1）按照质量份，准备5份三硬脂酸甘油酯作为固体脂质，5份2-辛基月桂醇作为液体脂质，1份Span80作为油包水型乳化剂；1份水杨酸作为祛痘活性物，1份氢氧化钠作为碱；1份失水山梨醇倍半油酸酯作为水包油型乳化剂。并准备壳聚糖1份、过氧化尿素0.1份、乙酸5份、甘油3份、环糊精15份。
（2）将乙酸配置成体积分数为2%的乙酸溶液，将壳聚糖溶于乙酸溶液中得到溶液1；将过氧化尿素溶于甘油中得的溶液2；将溶液2滴加到溶液1中，边加边搅拌，得到溶液3。
（3）将水杨酸和环糊精溶于去离子水中得到溶液4，将溶液3缓慢滴加到溶液4中，搅拌5h后于2℃静置18h，然后抽滤，并将得到的滤饼干燥，得到完成前处理的祛痘活性物。
（4）将固体脂质、液体脂质和油包水型乳化剂在60℃条件下混合均匀形成混合溶液，作为油相。将完成前处理的祛痘活性物、碱溶于去离子水，得到内水相。将水包油型乳化剂溶于去离子水中，得到外水相。
（5）将内水相加热至60℃后、在均质的条件下加至油相中，得到粗乳液，均质转速为15000rpm，均质时间为30s。降低粗乳液的温度至55℃，并将降温后的粗乳液在均质的条件下加至外水相中，得到乳液；均质转速为15000rpm，均质时间为1min。将乳液以500 rpm的转速磁力搅拌后冷却至常温，得到祛痘纳米脂质载体。
粒径的测定：取祛痘纳米脂质载体0.1m1，用9.9m1去离子水稀释100倍，用激光粒度仪（马尔文仪器）纳米ZS90检测粒径。粒径结果见图2，测得平均粒径为9.51μm，一致性为1.299，表明纳米粒粒径较小且均一。
实施例3
一种祛痘纳米脂质载体，通过以下方法制备：
（1）按照质量份，准备30份单硬酯酸甘油酯和月桂酸的等质量比混合物作为固体脂质，20份2-辛基月桂醇和亚油酸的等质量比混合物作为液体脂质，10份Span20作为油包水型乳化剂；10份水杨酸作为祛痘活性物，10份氢氧化钠作为碱；10份SSE-20作为水包油型乳化剂。并准备壳聚糖10份、过氧化尿素2份、乙酸20份、甘油8份、环糊精20份。
（2）将乙酸配置成体积分数为2%的乙酸溶液，将壳聚糖溶于乙酸溶液中得到溶液1；将过氧化尿素溶于甘油中得的溶液2；将溶液2滴加到溶液1中，边加边搅拌，得到溶液3。
（3）将水杨酸和环糊精溶于去离子水中得到溶液4，将溶液3缓慢滴加到溶液4中，搅拌8h后于5℃静置24h，然后抽滤，并将得到的滤饼干燥，得到完成前处理的祛痘活性物。
（4）将固体脂质、液体脂质和油包水型乳化剂在85℃条件下混合均匀形成混合溶液，作为油相。将完成前处理的祛痘活性物、碱溶于去离子水，得到内水相。将水包油型乳化剂溶于去离子水中，得到外水相。
（5）将内水相加热至85℃后、在均质的条件下加至油相中，得到粗乳液，均质转速为25000rpm，均质时间为60s。降低粗乳液的温度至75℃，并将降温后的粗乳液在均质的条件下加至外水相中，得到乳液；均质转速为25000rpm，均质时间为5min。将乳液以1200rpm的转速磁力搅拌后冷却至常温，得到祛痘纳米脂质载体。
实施例4
一种祛痘纳米脂质载体，通过以下方法制备：
（1）按照质量份，准备15份山嵛醇作为固体脂质，10份棕榈酸异丙酯作为液体脂质，8份Span40作为油包水型乳化剂；4份水杨酸作为祛痘活性物，2份氢氧化钠作为碱； 10份SSE-20作为水包油型乳化剂。并准备壳聚糖8份、过氧化尿素0.5份、乙酸18份、甘油5份、环糊精18份。
（2）将乙酸配置成体积分数为2%的乙酸溶液，将壳聚糖溶于乙酸溶液中得到溶液1；将过氧化尿素溶于甘油中得的溶液2；将溶液2滴加到溶液1中，边加边搅拌，得到溶液3。
（3）将水杨酸和环糊精溶于去离子水中得到溶液4，将溶液3缓慢滴加到溶液4中，搅拌6h后于4℃静置20h，然后抽滤，并将得到的滤饼干燥，得到完成前处理的祛痘活性物。
（4）将固体脂质、液体脂质和油包水型乳化剂在80℃条件下混合均匀形成混合溶液，作为油相。将完成前处理的祛痘活性物、碱溶于去离子水，得到内水相。将水包油型乳化剂溶于去离子水中，得到外水相。
（5）将内水相加热至80℃后、在均质的条件下加至油相中，得到粗乳液，均质转速为22000rpm，均质时间为40s。降低粗乳液的温度至72℃，并将降温后的粗乳液在均质的条件下加至外水相中，得到乳液；均质转速为20000rpm，均质时间为1min。将乳液以1000rpm的转速磁力搅拌后冷却至常温，得到祛痘纳米脂质载体。
本文中所描述的具体实施例仅仅是对本发明精神作举例说明。本发明所属技术领域的技术人员可以对所描述的具体实施例做各种各样的修改或补充或采用类似的方式替代，但并不会偏离本发明的精神或者超越所附权利要求书所定义的范围。
Claims (10)
1.一种祛痘纳米脂质载体，其特征在于：按照质量份，包括祛痘活性物1-10份、碱1-10份、固体脂质5-30份、液体脂质5-20份、油包水型乳化剂1-10份以及水包油型乳化剂1-10份。
2.根据权利要求1所述的一种祛痘纳米脂质载体，其特征在于：所述祛痘活性物选用水杨酸；按照质量份，还包括壳聚糖1-10份、过氧化尿素0.1-2份、乙酸5-20份、甘油3-8份、环糊精15-20份。
3.根据权利要求1所述一种祛痘纳米脂质载体，其特征在于：所述固体脂质包括十八醇、三山嵛酸甘油酯、胆固醇、三肉豆蔻酸甘油酯、棕榈酰硬脂酰甘油酯、三硬脂酸甘油酯、单硬酯酸甘油酯、山嵛醇、月桂酸、甘油硬脂酸酯柠檬酸酯、氢化蓖麻油、棕榈酸、棕榈醇、鲸蜡硬脂醇、脂肪醇和脂肪酸中的一种或几种。
4.根据权利要求1所述的一种祛痘纳米脂质载体，其特征在于：所述液体脂质包括辛酸癸酸三甘油酯、棕榈酸异丙酯、肉豆蔻酸异丙酯、液体石蜡、棕榈酸异辛酯月桂酸己酯、2-辛基月桂醇、油酸、亚油酸、大豆油和橄榄油中的一种或几种。
5.根据权利要求1所述的一种祛痘纳米脂质载体，其特征在于：所述油包水型乳化剂包括甘油酸酯枸橼酸酯、蔗糖硬脂酸酯、ABIL EM-90、P135、Span20、Span40、Span60、Span80、Brij 72、Brij 721、A6中的一种或几种。
6.根据权利要求1所述的一种祛痘纳米脂质载体，其特征在于：所述水包油型乳化剂包括失水山梨醇倍半油酸酯、SS、SSE-20、A25、Novel A、Tween20、Tween40、Tween60、Tween80、K12中的一种或几种。
7.一种根据权利要求1-6任意一项所述的祛痘纳米脂质载体的制备方法，其特征在于：包括以下步骤：
将固体脂质、液体脂质和油包水型乳化剂加热液化混合，得到油相；将祛痘活性物、碱溶于去离子水，得到内水相；将水包油型乳化剂溶于去离子水中，得到外水相；
将内水相加热至油相温度后、在均质的条件下加至油相中，得到粗乳液；降低5-10°粗乳液的温度，并将降温后的粗乳液在均质的条件下加至外水相中，得到乳液；将乳液磁力搅拌后冷却至常温，得到祛痘纳米脂质载体。
8.根据权利要求7所述的一种祛痘纳米脂质载体的制备方法，其特征在于：祛痘活性物还需进行前处理，包括以下步骤：
将乙酸配置成体积分数为2%的乙酸溶液，将壳聚糖溶于乙酸溶液中得到溶液1；将过氧化尿素溶于甘油中得的溶液2；将溶液2滴加到溶液1中，边加边搅拌，得到溶液3；
将水杨酸和环糊精溶于水中得到溶液4，将溶液3缓慢滴加到溶液4中，搅拌5-8h后于2-5℃静置18-24h，然后抽滤，并将得到的滤饼干燥，得到完成前处理的祛痘活性物。
9.根据权利要求7所述的一种祛痘纳米脂质载体的制备方法，其特征在于：油相加热温度为60-85℃。
10.根据权利要求7所述的一种祛痘纳米脂质载体的制备方法，其特征在于：均质转速均为15000-25000rpm。
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