CN111065376A - 包括积雪草提取物的共熔混合物的组合物 - Google Patents
包括积雪草提取物的共熔混合物的组合物 Download PDFInfo
- Publication number
- CN111065376A CN111065376A CN201880057550.3A CN201880057550A CN111065376A CN 111065376 A CN111065376 A CN 111065376A CN 201880057550 A CN201880057550 A CN 201880057550A CN 111065376 A CN111065376 A CN 111065376A
- Authority
- CN
- China
- Prior art keywords
- eutectic mixture
- mixture
- centella asiatica
- butter
- alcohol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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Abstract
提供一种共熔混合物,其包括积雪草提取物、黄油、表面活性剂、高级醇以及高级脂肪酸。使用该共熔混合物,可以提供包括积雪草提取物的各种剂型的组合物而没有析出现象。
Description
技术领域
本申请要求于2017年9月5日申请的韩国专利申请第10-2017-0113348号的优先权,所述说明书的全部是本申请的参考文献。
本公开涉及一种包括积雪草提取物的组合物。
背景技术
积雪草(Centella asiatica)也被称为积雪草(Centella),崩大碗,或老虎草(tiger herb),并且积雪草滴定提取物(Titrated Extract of Cetella asiatica:TECA)在医药学领域中用于多种用途。
在积雪草提取物中,积雪草(Centella asiatica)也被称为积雪草(Centella),崩大碗,或老虎草(tiger herb),并且积雪草滴定提取物(Titrated Extract of Cetellaasiatica:TECA)在医药学领域中用于多种用途。
积雪草提取物中含有积雪草皂苷(asiaticoside)、羟基积雪草酸(madecassicacid),以及积雪草酸(asiatic acid)作为主要成分,并且显示出皮肤伤口和慢性溃疡的治疗活性等。众所周知,积雪草皂苷和羟基积雪草酸涉及胶原蛋白的生成和分泌,因此具有提升受损皮肤的再生和真皮的弹性的效能。另外,近来,不仅医药品,用作功能性化妆品材料的需求正在增加。
积雪草提取物通常制造为高粘度类型的用于提高在皮肤的附着力的软膏剂型。然而,由于积雪草提取物的主要成分大多为难溶物质,因此对于纯净水的溶解度非常低。因此,为了提升积雪草提取物的溶解度,使用了将积雪草提取物以极性强的乙醇来溶解并在制备过程中添加其的方法。然而,在完成的剂型中,积雪草提取物的溶解度低,并且经常出现析出现象。为了解决这样的问题,使用过量增稠剂,或将产品的pH值保持在5.0以下,或添加过量乙醇,但是这样的方法仅限于特定剂型,并且难以应用于制造各种剂型的产品。
因此,需要在各种剂型中稳定地保持TECA的溶解度的方法。
发明内容
技术问题
提供一种积雪草提取物的共熔混合物。
技术方案
一方面提供一种共熔混合物,包括积雪草提取物、黄油、表面活性剂、高级醇,以及高级脂肪酸。
“共熔混合物(eutectic mixture)"是指由两种或多种不同成分组成的混合物,或如由一种成分组成的固体化合物具有恒定熔点,即共晶(共熔晶)的混合物。由于共熔混合物具有恒定熔点,尽管在表面上看起来是均匀的,但实际上,可以混合几种细微不同的结晶。
所述共熔混合物可以包括2%(w/w)至8%(w/w),3%(w/w)至7%(w/w),4%(w/w)至6%(w/w),或约5%(w/w)的所述积雪草提取物。所述积雪草提取物可以包括积雪草滴定提取物(Titrated Extract of Centella asiatica:TECA)。在TECA中可以包括约40%的积雪草皂苷(asiaticoside)、约40%的羟基积雪草酸(madecassic acid),以及约20%的积雪草酸(asiatic acid)。所述积雪草提取物可以以诸如水和乙醇等的适当的溶剂稀释TECA的。所述积雪草提取物可以作为药物组合物或化妆品组合物的原料在商业上售卖。所述积雪草提取物可以由本领域技术人员根据食物和医药品安全部的医药品标准和已知的提取物制法来容易地制造。
所述积雪草提取物可以包括20%(w/w)至60%(w/w)、25%(w/w)至55%(w/w)、30%(w/w)至50%(w/w)、35%(w/w)至45%(w/w),或约40%(w/w)的所述黄油。所述黄油可以包括植物性黄油。所述植物性黄油可以包括乳木果油、可可油、芒果籽油、大花可可树籽脂、椰子籽油,或其混合物。
所述共熔混合物可以包括10%(w/w)至40%(w/w)、15%(w/w)至35%(w/w)、20%(w/w)至30%(w/w),或约25%(w/w)的所述表面活性剂。所述表面活性剂可以包括甘油硬脂酸酯、PEG-40硬脂酸酯、PEG-100硬脂酸酯、聚山梨酯60、甘油硬脂酸酯SE、或其混合物。
所述共熔混合物可以包括5%(w/w)至25%(w/w)、10%(w/w)至20%(w/w),或约15%(w/w)的所述高级醇。所述高级醇可以包括鲸蜡醇、硬脂醇、山嵛醇、鲨肝醇,或其混合物。
所述共熔混合物可以包括5%(w/w)至25%(w/w)、10%(w/w)至20%(w/w),或约15%(w/w)的所述高级脂肪酸。所述高级脂肪酸可以包括硬脂酸、异硬脂酸、肉豆蔻酸、软脂酸,或其混合物。
另一方面提供包括所述共熔混合物的化妆品组合物。
所述化妆品组合物可以制造为化妆水(润肤液)、柔肤液、爽肤水、收敛剂、乳液、牛奶乳液、保湿乳液、营养乳液、按摩霜、营养乳霜、保湿乳霜、手霜、粉底、精华素、营养精华素、面膜、肥皂、洁面泡沫、洁面液、洁面霜、身体润肤液、沐浴露、悬浮液、凝胶、粉末、糊剂、面膜或片装面膜,或包括气雾剂组合物的剂型。这样的剂型可以根据本领域常规方法来制造。
除了上述成分之外,所述化妆品组合物还可以包括诸如保存剂、稳定化剂、表面活性剂、增稠剂、溶解剂、保湿剂、软化剂、紫外线吸收剂、防腐剂、杀菌剂、乳化剂、抗氧化剂、pH调节剂、有机和无机颜料、香料、冷感剂,或止汗剂等的本领域常用的添加剂。所述保存剂等的额外成分的配合量可以由本领域技术人员在不损害本公开的目的和效果的范围内容易地选择,所述配合量可以为基于组合物总重量的0.001%(w/w)至30%(w/w),具体地为0.01%(w/w)至10%(w/w)。
另一方面提供包括所述共熔混合物的皮肤外用剂组合物。
所述皮肤外用剂组合物可以制造为本领域通常制造的任何剂型,例如,包括乳液、乳霜、化妆水、面膜、粉底、乳液、美容液,毛发化妆品等。具体地,包括润肤液、柔肤液、爽肤水、收敛剂、乳液、牛奶乳液、保湿乳液、营养乳液、按摩霜、营养乳霜、保湿乳霜、手霜、粉底、精华、营养精华、面膜、肥皂、洁面泡沫、洁面液、洁面霜、身体润肤液、和沐浴露的剂型。
所述化妆品组合物或皮肤外用剂组合物可以为水包油(O/W)的剂型。
所述组合物的水相部可以包括1.0%(w/w)至20%(w/w)的保湿剂,和0.01%(w/w)至5.0%(w/w)的增稠剂。保湿剂可以包括甘油、1.3丁二醇、丙二醇、戊二醇,或其混合物,以防止在低温下连续相的冻结并有助于保湿效果。增稠剂可以包括卡波姆、瓜尔豆胶、卡拉胶、黄原胶、羧甲基纤维素、羟乙基纤维素、羟丙基纤维素、聚丙烯酸酯-13、聚丙烯酰胺、丙烯酸钠/丙烯酰二甲基牛磺酸钠共聚物、羟基乙基丙烯酸酯/丙烯酰二甲基牛磺酸钠共聚物,或其混合物,以控制连续相的粘度。
所述组合物的油相物可以包括1.0%(w/w)至30.0%(w/w)的润肤油、0.1%(w/w)至10.0%(w/w)的乳化剂,和0.1%(w/w)至10.0%(w/w)的蜡。所述软化剂油可以包括各种酯类油、澳洲堅果油、荷荷巴油、包括蓖麻油的各种植物性油、角鲨烷、矿物油、异十六烷、矽油,或其混合物。所述乳化剂可以包括鲸蜡基PEG/PPG-10/1聚二甲基硅氧烷、PEG-10聚二甲基硅氧烷、硬脂醇聚醚-21和硬脂醇聚醚-2、聚甘油-2二聚羟基硬脂酸酯、聚甘油-3聚蓖麻醇酸酯、聚甘油-3甲基葡糖二硬脂酸酯、甘油硬脂酸酯、PEG-40硬脂酸、PEG-100硬脂酸、聚山梨酯60、3-甘油硬脂酸酯SE甘油硬脂酸酯,或其混合物。所述蜡可以包括蜂蜡、小烛树蜡、巴西蜡棕蜡、多蜡(multiwax)、石蜡、微晶蜡、纯地蜡,或其混合物。
由于所述组合物包括积雪草提取物,因此可以用于改善或治疗皮肤损伤,如皮肤保湿、皮肤镇静、皮肤保护、皱纹改善等。
另一方面提供一种制造共熔混合物的方法,包括:混合积雪草提取物、黄油、表面活性剂、高级醇,和高级脂肪酸并加热至65℃至80℃后搅拌来获得混合物的步骤;将所述混合物以20rpm至40rpm搅拌并同时冷却至45℃至60℃后再次以4000rpm至8000rpm搅拌来获得混合物的步骤;以及将所述混合物以20rpm至40rpm搅拌并同时冷却至室温的步骤。
所述冷却可以通过使用温度保持在0℃至20℃的冷却浴来进行,并且可以不考虑时间进行冷却,直到混合物达到期望的温度。所述冷却可以与20rpm至40rpm的适当水平的搅拌一起进行。
在冷却后搅拌混合物的步骤可以通过使用4000rpm至8000rpm的搅拌器来进行,并且可以进行如1如1至30分钟至30分钟、2分钟至20分钟,或3分钟至10分钟等直到混合物充分混合。
有益效果
包括积雪草提取物、黄油、表面活性剂、高级醇,以及高级脂肪酸的共熔混合物可以提供包括其的多种剂型的组合物而没有析出现象。
附图说明
图1a是示出包括比较例5的O/W化妆品组合物的外观的照片。
图1b是示出包括比较例6的O/W化妆品组合物的外观的照片。
图1c是示出包括实施例18的O/W化妆品组合物的外观的照片。
图2a是示出在包括比较例5的O/W化妆品组合物中出现析出现象的显微镜图像。
图2b是示出在包括比较例6的O/W化妆品组合物中出现析出现象的显微镜图像。
图2c是示出在包括实施例18的O/W化妆品组合物中出现析出现象的显微镜图像。
具体实施方式
在下文中,将通过实施例更详细地描述本公开。然而,这些实施例仅用于说明本公开,本公开的范围不限于这四个实施例。
1.制造包括黄油类、表面活性剂、高级醇和高级脂肪酸的共熔混合物
通过在TECA中添加黄油类、表面活性剂、高级醇和高级脂肪酸来制造共熔混合物。具体地,使用各种黄油类、表面活性剂、高级醇和高级脂肪酸根据在下表1-4中所述的组成并根据以下(a)-(c)步骤来制造含有TECA的共熔混合物。在表1-4中各成分的组成取决于重量百分比。
(a)混合各成分并加热(70℃~75℃)后,使用超高速搅拌器(PRIMIX,Homomixmarker II 2.5)均匀混合。
(b)将在所述(a)中获得的混合物在保持在10℃的冷却浴槽中以25rpm搅拌的同时冷却(50℃~55℃),然后使用超高速搅拌器以6000rpm均匀混合5分钟。
(c)将在所述(b)中获得的混合物在保持在10℃的冷却浴槽中以25rpm搅拌的同时冷却(30℃)来获得共熔混合物。
[表1]根据更换黄油类制造共熔混合物
成分 | 比较例1 | 实施例1 | 实施例2 | 实施例3 | 实施例4 | 实施例5 |
TECA | 5.0 | 5.0 | 5.0 | 5.0 | 5.0 | 5.0 |
乳木果油 | - | 40.0 | - | - | - | - |
可可油 | - | - | 40.0 | - | - | - |
芒果籽油 | - | - | - | 40.0 | - | - |
大花可可树籽脂 | - | - | - | - | 40.0 | - |
椰子籽油 | - | - | - | - | - | 40.0 |
甘油硬脂酸酯 | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 |
PEG-100硬脂酸酯 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 |
鲸蜡硬脂醇 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 |
硬脂酸 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 |
根据制造结果,在实施例1-5的情况下,获得浅黄色不透明蜡状组合物,相反,在比较例1的情况下,获得每种TECA沉淀并分离的组合物。
[表2]根据更换表面活性剂制造共熔混合物
成分 | 比较例2 | 实施例6 | 实施例7 | 实施例8 | 实施例9 |
TECA | 5.0 | 5.0 | 5.0 | 5.0 | 5.0 |
乳木果油 | 40.0 | 40.0 | 40.0 | 40.0 | 40.0 |
甘油硬脂酸酯 | - | 10.0 | - | - | - |
PEG-100硬脂酸酯 | - | 15.0 | 10.0 | - | - |
PEG-40硬脂酸酯 | - | - | 15.0 | 10.0 | |
聚山梨酯60 | - | - | - | 15.0 | 10.0 |
甘油硬脂酸酯SE | - | - | - | - | 15.0 |
鲸蜡硬脂醇 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 |
硬脂酸 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 |
根据制造结果,在实施例6-9的情况下,获得浅黄色不透明蜡状组合物,相反,在比较例2的情况下,获得TECA析出的组合物。
[表3]根据更换高级醇和高级脂肪酸制造共熔混合物
根据制造结果,在实施例10-13的情况下,获得浅黄色不透明蜡状组合物,相反,在比较例3的情况下,获得TECA沉淀的组合物。
[表4]根据更换高级脂肪酸制造共熔混合物
成分 | 比较例4 | 实施例14 | 实施例15 | 实施例16 | 实施例17 |
TECA | 5.0 | 5.0 | 5.0 | 5.0 | 5.0 |
乳木果油 | 40.0 | 40.0 | 40.0 | 40.0 | 40.0 |
甘油硬脂酸酯 | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 |
PEG-100硬脂酸酯 | 15.0 | 15.0 | 15.0 | 15.0 | 15.0 |
鲸蜡硬脂醇 | 15.0 | 15.0 | - | - | - |
硬脂酸 | - | 15.0 | - | - | - |
异硬脂酸 | 15.0 | - | - | ||
肉豆蔻酸 | 15.0 | - | |||
软脂酸 | 15.0 |
根据制造结果,在实施例14-17的情况下,获得浅黄色不透明蜡状组合物,相反,在比较例4的情况下,获得TECA沉淀的组合物。
2.制造O/W乳液
以如以下表5所示的组成应用TECA共熔混合物来制造O/W皮肤外用剂,并且制造方法如以下(a)-(e)。
[表5]制造使用TECA共熔混合物的O/W皮肤外用剂
a)混合表5的水性相成分并加热(70℃~75℃),然后均匀混合来获得混合物。
(b)混合表5的油性相成分并加热(70℃~75℃),然后均匀混合来获得混合物。
(c)在所述(a)的混合物放入(b)的混合物并均匀混合。
(d)将在所述(c)中获得的混合物冷却(45℃),然后在其中放入防腐剂和香料,并均匀混合。
(e)将在所述(d)中获得的混合物冷却至30℃。
图1a、1b,和1c是分别示出包括比较例5、比较例6,和实施例18的O/W化妆品组合物的外观的照片,图2a、2b,及2c是分别示出在包括比较例5、比较例6,和实施例18的O/W化妆品组合物中出现析出现象的显微镜图像。根据制造结果,比较例5是通过将TECA、黄油、表面活性剂、高级醇,和高级脂肪酸的简单混合物添加至油相而制备的,确认了其在约一周内出现析出,并且TECA不能溶解。
比较例6是通过将比较例1-4中的任何一个添加至油相中而制备的,观察了其在4℃、25℃、37℃,和45℃下4周内出现TECA的析出。
实施例18是通过将根据实施例1~17制造的共熔混合物中的任何一个添加至油相中而制备的,观察了其在4℃、25℃、37℃,和45℃下8周期间没有出现析出。
Claims (9)
1.一种共熔混合物,包括积雪草提取物、黄油、表面活性剂、高级醇以及高级脂肪酸。
2.根据权利要求1所述的共熔混合物,其中,所述积雪草提取物为积雪草滴定提取物。
3.根据权利要求1所述的共熔混合物,其中,所述共熔混合物包括按重量百分比计2%至8%的积雪草提取物、30%至50%的黄油、15%至35%的表面活性剂、5%至25%的高级醇以及5%至25%的高级脂肪酸。
4.根据权利要求1所述的共熔混合物,其中,所述黄油包括乳木果油、可可油、芒果籽油、大花可可树籽脂和椰子籽油中的至少一者。
5.根据权利要求1所述的共熔混合物,其中,所述表面活性剂包括甘油硬脂酸酯、PEG-40硬脂酸酯、PEG-100硬脂酸酯、聚山梨酯60和甘油硬脂酸酯SE中的至少一者。
6.根据权利要求1所述的共熔混合物,其中,所述高级醇包括鲸蜡醇、硬脂醇、山嵛醇和鲨肝醇中的至少一者。
7.根据权利要求1所述的共熔混合物,其中,所述高级脂肪酸包括硬脂酸、异硬脂酸、肉豆蔻酸和软脂酸中的至少一者。
8.一种皮肤外用剂组合物,其包括根据权利要求1所述的共熔混合物。
9.一种制造共熔混合物的方法,包括:
步骤a:混合积雪草提取物、黄油、表面活性剂、高级醇和高级脂肪酸并加热至65℃至80℃后搅拌以获得混合物;
步骤b:将在步骤a中获得的混合物以20rpm至40rpm搅拌并同时冷却至45℃至60℃后,再次以4000rpm至8000rpm搅拌来获得混合物;以及
步骤c:将在步骤b中获得的混合物以20rpm至40rpm搅拌并同时冷却至室温。
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