CN116650348A - 甘草素的用途、脂质体及其应用 - Google Patents
甘草素的用途、脂质体及其应用 Download PDFInfo
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- CN116650348A CN116650348A CN202310791897.3A CN202310791897A CN116650348A CN 116650348 A CN116650348 A CN 116650348A CN 202310791897 A CN202310791897 A CN 202310791897A CN 116650348 A CN116650348 A CN 116650348A
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- liposome
- avobenzone
- glycyrrhizin
- homogenization
- water
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- A61K8/00—Cosmetics or similar toiletry preparations
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- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/14—Liposomes; Vesicles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
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- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
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Abstract
本发明公开了一种甘草素稳定阿伏苯宗的新用途,还公开一种阿伏苯宗的脂质体及其应用。甘草素可以有效的增强阿伏苯宗的光稳定性,且能提升防晒配方的SPF值和PA值。脂质体溶解性好,防晒指数高,还可以均匀分布于皮肤表面且不渗透皮肤,避免了防晒剂对人体内分泌的影响。
Description
技术领域
本发明属于防晒剂领域,具体涉及将甘草素稳定阿伏苯宗的新用途,含有甘草素和阿伏苯宗的脂质体及其应用。
背景技术
阿伏苯宗AVB是目前法规批准的最强的UVA紫外线吸收剂,也是使用最广泛的紫外线吸收剂。但该原料的光稳定性不好,在日光下其防护能力会迅速减弱,且存在与某些原料的配伍禁忌。如与肉桂酸辛酯(OMC)合用时,可以形成新的化合物,且此化合物对紫外线没有吸收能力。
现有技术中常使用奥克立林、苯基苯并咪唑磺酸来稳定AVB。奥克立林需要达到3倍于AVB的添加量,才能有可以接受的稳定效果。而苯基苯并咪唑磺酸存在溶解性问题,常用碱盐溶解,导致配方离子浓度过高,影响稳定性。另外,AVB是有机防晒剂,有机防晒剂涂布于皮肤上时存在渗透的风险。如二苯酮-3和甲氧基肉桂酸辛酯,可以被皮肤吸收进入血液和尿液。体内和体外研究报道这两种防晒剂对人体内分泌存在干扰。
因此,要得到较佳的防晒效果就需要将阿伏苯宗稳定下来,进一步地,又要使得防晒剂不能渗透皮肤对人体产生伤害风险。为此,人们一直寻找一种解决办法。
发明内容
为了克服现有技术中存在的不足,本发明提供一种用甘草素来稳定阿伏苯宗的新用途,还提供一种脂质体、含有该脂质体的防晒霜以及所述脂质体在个人护理产品中的应用。
本发明的技术方案为:
一种甘草素的用途,它用于稳定阿伏苯宗。甘草素为中药提取物,也称为甘草醇、甘草甜素等,常用于抗皮肤敏感,近些年也有文献公开用于抗癌,申请人偶然发现甘草素可用于稳定阿伏苯宗,增强阿伏苯宗的光稳定性,且能提升含有阿伏苯宗防晒成分配方的SPF值和PA值。应用时甘草素与阿伏苯宗的质量配比为1:5-23,更优选为1:9-13。应用时甘草素与阿伏苯宗可以一起做成乳液、脂质体乳液、膏霜、防晒棒、防晒喷雾等。
本发明公开一种脂质体,所述脂质体包含阿伏苯宗和甘草素,脂质体形态有助于提高阿伏苯宗及甘草素的溶解性。
优选地,以所述脂质体的总质量为基准,所述脂质体中阿伏苯宗、稳定剂、助乳化剂和脂质体材料的占比分别为30.0~55.0%、2.0~6.0%、8.0~15.0%和1.0~3.5%,余量为水。
优选地,为了使脂质体不渗透皮肤,避免了人体吸收,所述脂质体的粒径大于800nm。
优选地,为了使脂质体均匀分布于皮肤表面且不渗透皮肤,所述脂质体的粒径大于800nm,且小于1200nm。
优选地,所述脂质体材料为磷脂或氢化磷脂。
优选地,为了得到稳定的脂质体,所述脂质体材料中磷脂酰胆碱的含量在75wt%以上。
优选地,为了提高其稳定性,所述甘草素的纯度在80wt%以上。
优选地,基于成本、易得性和促乳化性考虑,所述助乳化剂为多元醇,所述多元醇为甘油、己二醇、丁二醇和丙二醇中的一种或几种。
本发明公开一种所述脂质体的制备方法,包括以下步骤,
S1.将阿伏苯宗融化,然后加入甘草素得油相;
S2.将助乳化剂和脂质体材料混合并溶解,加水混合得水相;
S3.将所述油相加入所述水相中,高压均质;
优选地,为了平衡成本及生产效率,步骤S1的融化温度为55-80℃,步骤S2中的溶解温度为50-70℃。为了平衡能耗和所得脂质体的粒径,步骤S3中高压均质的次数为3-10次,均质压力为500~1000bar。更优选步骤S3中高压均质的次数为3-5次,均质压力为700~1000bar。
所述脂质体可以使得阿伏苯宗具有光稳定性,适用于个人防晒产品,本发明还公开一种含有所述脂质体的防晒霜。
优选地,所述防晒霜以总质量为基准,包括2-5%乳化剂、3-6%油脂、2-5%保湿剂、0.2-1%增稠剂和10-22%脂质体,余量为水。
其中,所述乳化剂选自蔗糖脂肪酸酯、失水山梨醇类、聚氧乙烯类、脂肪酸酯类、脂肪酸皂类、POE蓖麻油或氢化蓖麻油衍生物或烷基糖苷类。
其中,所述油脂选自辛酸/癸酸甘油三酯、肉豆蔻酸异丙酯、辛酸十六烷基酯、肉豆蔻酸辛基十二烷基酯、棕榈酸异丙酯、硬脂酸丁酯、月桂酸己酯、肉豆蔻酸肉豆蔻酯、霍霍巴油、甜杏仁油、橄榄油、角鲨烷、角鲨烯、羊毛脂及其衍生物、小麦胚芽油、山茶花油、蓖麻油、亚麻子油、红花油、紫苏子油、大豆油、花生油、茶籽油、椰子油、沙棘果油、乳木果油、月见草油、或硅油。
其中,所述保湿剂选自丙二醇、丙三醇、透明质酸钠、普鲁兰多糖、银耳多糖、褐藻糖胶、聚谷氨酸、β-葡聚糖和海藻糖、PCA钠或胶原蛋白肽;
其中,所述增稠剂选自瓜尔豆胶或其衍生物、卡拉胶、半乳聚糖、阿拉伯胶、果胶、甘露聚糖、淀粉或其衍生物、黄原胶、甲基纤维素、羟乙基纤维素、羧甲基纤维素、甲基羟基丙基纤维素、聚乙烯吡咯烷酮、羧基乙烯基聚合物、烷基改性羧基乙烯基聚合物、聚丙烯酸聚合物类、聚乙二醇、膨润土或卡波。
本发明还公开一种所述脂质体在个人护理产品中的应用。
本发明的有益效果如下:
(1)甘草素作为植物提取物,可增强阿伏苯宗的光稳定性,安全性高。
(2)本发明防晒剂脂质体溶解性好,其中防晒剂含量为30-55%,防晒指数高。
(3)发明的脂质体粒径可控制在800nm以上,可以均匀分布于皮肤表面且不渗透皮肤,避免了防晒剂对人体内分泌的影响。
(4)本发明的防晒剂脂质体,适用于于冷配工艺,产品成本低/稳定性好。
(5)因甘草素增强了阿伏苯宗的光稳定性,本发明的防晒霜SPF值和PA值高。
(6)因甘草素增强了阿伏苯宗的光稳定性,使得含有甘草素和阿伏苯宗的脂质体可广泛用于具有防晒作用的个人护理品中。
附图说明
图1为实施例4的透射电镜图
具体实施方式
下面对本发明作更进一步的说明,本发明实施例所用的实验方法如无特殊说明,均为常规方法。本发明实施例所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
实验原料 | 规格 | 厂家 |
阿伏苯宗 | 99.0wt% | 宜都华阳化工有限责任公司 |
磷脂 | 75wt%PC | LipoidAG |
甘草素 | 90wt% | 青海湖药业有限公司 |
实施例及对比例配方如表1所示,防晒剂脂质体的制备方法如下:
(1)按表1所述的乳化剂、油酯在70℃下融化完全,得油相;
(2)将磷脂、甘草素和多元醇混合并在65℃下溶解,加水得水相;
(3)将油相缓慢加入水相中,进行高压均质,均质次数3次,均质压力为700bar,即得。
表1实施例及对比例组分列表
一、防晒剂脂质体的粒径和多分散系数的测定
粒径测定方法如下:用超纯水按1:10的质量比稀释脂质体后,取适量溶液加入到样品池中。采用粒径分析仪ZetasizerNano ZS90测定脂质体的粒径和多分散系数(PDI)。考察结果见表2。
表2.防晒脂质体粒径和多分散系数的测定结果
粒径,nm | PDI | |
实施例1 | 220.0±1.5 | 0.232±0.142 |
实施例2 | 305.2±2.0 | 0.101±0.077 |
实施例3 | 820.1±4.5 | 0.204±0.101 |
实施例4 | 905.7±5.1 | 0.141±0.089 |
实施例5 | 600.2±3.4 | 0.472±0.202 |
实施例6 | 960.4±4.2 | 0.156±0.103 |
实施例7 | 408.3±2.2 | 0.453±0.210 |
实施例8 | 360.6±2.3 | 0.214±0.134 |
实施例9 | 540.6±3.2 | 0.305±0.189 |
对比例1 | 759.1±4.0 | 0.121±0.075 |
对比例2 | 802.3±4.0 | 0.215±0.121 |
磷脂脂质体由于较强的亲脂性主要停留在角质层,且由于其弹性差难以穿越角质层。当磷脂脂质体的粒径较小时,会渗透入皮肤表面的毛囊。有研究表明,小于640nm的脂质体即可进入毛囊,表现出更多的蓄积性和渗透力。因此,本发明的脂质体粒径可控制在800nm以上,最大限度的减少对皮肤的渗透。
由上述结果可以看出实施例3、实施例4和实施例6的纳米粒径大于800nm,PDI较小(低于0.30),粒径分布均匀,具有很好的稳定性、安全性和应用性。
采用透射电镜对实施例4进行形态学观察。透射电镜图如图1所示。结果表明防晒脂质体的形态为类球性粒子,粒径与粒度仪所测结果一致,平均粒径在900nm左右。
二、防晒剂脂质体的包封率的测定
取实施例3、实施例4和实施例6的脂质体,分别置于超滤离心管内管中,在4000rpm离心10分钟,然后取滤液。参照USP方法测游离阿伏苯宗的含量,色谱条件为:色谱柱SE-30,0.32-mm×25-m或类似色谱柱,流速2mL/min,载气为氦气,进样量1μL,进样温200℃,检测温度280℃,分流比50:1,运行时间15min。按以下公式计算包封率,结果见表3。
包封率(%)=(W1-W2)/W1×100%
其中,W1为防晒脂质体的称样量,W2为游离阿伏苯宗的含量。
表3防晒脂质体的包封率测定结果
实施例 | 包封率,% |
实施例3 | 92.4±1.5 |
实施例4 | 90.5±2.1 |
实施例6 | 88.4±2.7 |
对比例1 | 91.5±2.0 |
对比例2 | 92.1±2.1 |
由上述结果可以看出实施例3、实施例4和实施例6的包封率均达到要求,其中实施例3的包封率最高,将具有很好的稳定性和应用性。
三、均质次数和均质压力对防晒剂脂质体的影响
按实施例4配比制备样品,采用均质压力分别为500bar、700bar和1000bar,均质次数分别为3,5和10次。考察结果见下表4。
表4均质压力和次数对脂质体的影响
均质压力和次数 | 粒径,nm | PDI | 包封率,% |
500bar,3次 | 1040±5.6 | 0.198±0.104 | 85.0±1.9 |
700bar,3次 | 890.7±5.0 | 0.166±0.108 | 90.5±2.0 |
1000bar,3次 | 620.5±4.3 | 0.125±0.087 | 91.3±2.9 |
500bar,5次 | 760.4±4.7 | 0.175±0.094 | 86.3±1.8 |
700bar,10次 | 426.2±2.6 | 0.128±0.088 | 87.1±2.1 |
结果表明,不同的均质压力和次数的条件下,防晒脂质体都具有小的PDI和较高的包封率。但均质次数越多、均质压力越大,脂质体的粒径会减小且瞬时和出料温度会升高5-10℃,且能耗增大。所以综合各因素,本发明的高压均质的最佳条件为:均质压力700bar,均质循环次数3次。
四、甘草素对阿伏苯宗的稳定作用
按表5配制防晒霜,按照《化妆品安全技术规范》(2015年版)的测试方法,分别在光照0、2、4、6、8小时后测试防晒霜的SPF和UVA PF值,结果见表6和表7。
具体配制方法如下:
(1)将乳化剂 SUCRO和辛酸/癸酸甘油三酯混合,并在75℃下溶解完全,得油相(应用对比例1中阿伏苯宗在步骤(1)中加入);
(2)将保湿剂甘油、增稠剂黄原胶和水在75℃下溶解完全后得水相;
(3)将油相加入水相,均质3~5min,然后在40℃下边搅拌边加入脂质体,混合均匀,即得。
表5.防晒霜配方表(份数)
表6.应用对比例和应用例的SPF测试结果
表7.应用对比例和应用例的UVA PF值测试结果
从表6和表7可以看出,甘草素可以有效的增强阿伏苯宗的光稳定性,且能提升配方的SPF值和PA值。
以上所述仅是本发明的优选实施方式,应当指出:对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (10)
1.甘草素的用途,其特征在于,它用于稳定阿伏苯宗。
2.一种脂质体,其特征在于,所述脂质体包含阿伏苯宗和甘草素。
3.如权利要求2所述的脂质体,其特征在于,以所述脂质体的总质量为基准,所述脂质体中阿伏苯宗、稳定剂、助乳化剂和脂质体材料的占比分别为30.0~55.0%、2.0~6.0%、8.0~15.0%和1.0~3.5%,余量为水。
4.如权利要求2所述的脂质体,其特征在于,所述脂质体的粒径大于800nm;所述脂质体的粒径大于800nm,且小于1200nm。
5.如权利要求3或4所述的脂质体,其特征在于,所述脂质体材料为磷脂或氢化磷脂;所述脂质体材料中磷脂酰胆碱的含量在75wt%以上。
6.如权利要求3或4所述的脂质体,其特征在于,所述甘草素的纯度在80wt%以上。
7.如权利要求3-6任一项所述的脂质体,其特征在于,所述助乳化剂为多元醇;所述多元醇为甘油、己二醇、丁二醇和丙二醇中的一种或几种。
8.一种如权利要求2-7任一项所述的脂质体的制备方法,包括以下步骤,
S1.将阿伏苯宗融化,然后加入甘草素得油相;
S2.将助乳化剂和脂质体材料混合并溶解,加水混合得水相;
S3.将所述油相加入所述水相中,高压均质即得;
步骤S1的融化温度为55-80℃,步骤S2中的溶解温度为50-70℃,步骤S3中高压均质的次数为3-10次,均质压力为500~1000bar;步骤S3中高压均质的次数为3-5次,均质压力为700~1000bar。
9.一种含有权利要求2-7所述脂质体的防晒霜;所述防晒霜以总质量为基准,包括2-5%乳化剂、3-6%油脂、2-5%保湿剂、0.2-1%增稠剂和10-22%脂质体,余量为水。
10.一种如权利要求2-7所述脂质体在个人护理产品中的应用。
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