CN113509442A - 一种含补骨脂酚的脂质体及其制备方法 - Google Patents
一种含补骨脂酚的脂质体及其制备方法 Download PDFInfo
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- LFYJSSARVMHQJB-QIXNEVBVSA-N bakuchiol Chemical compound CC(C)=CCC[C@@](C)(C=C)\C=C\C1=CC=C(O)C=C1 LFYJSSARVMHQJB-QIXNEVBVSA-N 0.000 title claims abstract description 61
- LFYJSSARVMHQJB-UHFFFAOYSA-N Backuchiol Natural products CC(C)=CCCC(C)(C=C)C=CC1=CC=C(O)C=C1 LFYJSSARVMHQJB-UHFFFAOYSA-N 0.000 title claims abstract description 60
- LFYJSSARVMHQJB-GOSISDBHSA-N bakuchinol Natural products CC(C)=CCC[C@@](C)(C=C)C=CC1=CC=C(O)C=C1 LFYJSSARVMHQJB-GOSISDBHSA-N 0.000 title claims abstract description 60
- 229940117895 bakuchiol Drugs 0.000 title claims abstract description 60
- KXXXNMZPAJTCQY-UHFFFAOYSA-N bakuchiol Natural products CC(C)CCCC(C)(C=C)C=Cc1ccc(O)cc1 KXXXNMZPAJTCQY-UHFFFAOYSA-N 0.000 title claims abstract description 60
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Abstract
本发明公开了一种含补骨脂酚的脂质体及其制备方法,补骨脂酚脂质体,包括以下重量份数的原料:补骨脂酚3‑8份、卵磷脂3‑8份、胆甾醇0.5‑1.5份、辛酸/癸酸甘油三酯5‑15份、1,3‑丙二醇15‑30份、乙酰化透明质酸钠1‑3份和水50‑65份;其制备方法包括将补骨脂酚、卵磷脂和胆甾醇加入到辛酸/癸酸甘油三酯和1,3‑丙二醇中,融解,得油相;将乙酰化透明质酸钠,加入水中溶解,得水相;将有油相加入水相中,高压均质,得含补骨脂酚的脂质体。本发明具有对皮肤刺激小、透皮吸收效果好的特点。
Description
技术领域
本发明涉及一种补骨脂酚脂质体,特别是一种含补骨脂酚的脂质体及其制备方法。
背景技术
补骨脂酚是从草本植物补骨脂籽中提取出来的酚类物质,是一种异戊二烯基酚萜类化合物,实验研究和临床实验中发现其具有控油、抗炎、抗痤疮的活性,还具有抗氧化、抗衰老、美白的效果,可以改善皱纹、减少色素沉着,安全性高。但是补骨脂酚的保存条件比较苛刻,易氧化,并且由于皮肤角质层的存在,补骨脂酚直接作用于皮肤时,其吸收会受到很大的限制,透过率较低,透皮吸收效果较差,从而影响补骨脂酚的应用。
由磷脂、20%~50%乙醇和水组成的脂质体(liposome),是一种乙醇含量很高的纳米给药载体,具有流动性好、变形性强、包封率高、稳定性好、刺激性小等优点,可通过包封增加药物的溶解度,促进药物的经皮吸收,并在角质层形成药物贮库,起到缓释作用,避免药物大量进入血液,引起全身性反应。其中,脂质体的组成极大的影响其包封率和透皮性能,脂质体中的乙醇含量很高,虽然可以降低脂质体之间的水合力,但过量可导致脂质体的聚集与融合,而且乙醇对皮肤具有刺激性,容易导致过敏反应,不适合敏感性皮肤使用。
发明内容
本发明的目的在于,提供一种含补骨脂酚的脂质体及其制备方法。本发明具有对皮肤刺激小、透皮吸收效果好的特点。
本发明的技术方案:一种含补骨脂酚的脂质体,包括以下重量份数的原料:补骨脂酚3-8份、卵磷脂3-8份、胆甾醇0.5-1.5份、辛酸/癸酸甘油三酯5-15份、1,3-丙二醇15-30份、乙酰化透明质酸钠1-3份和水50-65份。
前述的一种含补骨脂酚的脂质体中,包括以下重量份数的原料:补骨脂酚5份、卵磷脂5份、胆甾醇1份、辛酸/癸酸甘油三酯10份、1,3-丙二醇20份、乙酰化透明质酸钠2份和水57份。
前述的一种含补骨脂酚的脂质体中,所述卵磷脂中磷脂酰胆碱的含量在70%以上。
上述的含补骨脂酚的脂质体的制备方法,包括以下步骤:
步骤一、称取补骨脂酚、卵磷脂和胆甾醇加入到辛酸/癸酸甘油三酯和1,3-丙二醇中,于60-80℃下搅拌融解,得油相;
步骤二、称取乙酰化透明质酸钠,加入水中,于60-80℃下搅拌溶解,得水相;
步骤三、将有油相加入水相中,搅拌20-40min,得到初步混合液,将初步混合液通过高压均质机在500-1500bar下均质循环3-8次,得含补骨脂酚的脂质体。
前述的制备方法中,包括以下步骤:
步骤一、称取补骨脂酚、卵磷脂和胆甾醇加入到辛酸/癸酸甘油三酯和1,3-丙二醇中,于70℃下搅拌融解,得油相;
步骤二、称取乙酰化透明质酸钠,加入水中,于70℃下搅拌溶解,得水相;
步骤三、将油相加入水相中,搅拌30min,得到初步混合液,将初步混合液用高压均质机在1000bar的条件下均质循环5次,得含补骨脂酚的脂质体。
与现有技术相比,本发明采用1,3-丙二醇代替乙醇与卵磷脂和胆甾醇形成脂质体,产品中不含乙醇,1,3-丙二醇性能温和,减少对皮肤的刺激,适合敏感性皮肤。改善脂质体稳定性欠佳的问题,使其更易于保存;
将补骨脂酚有效成分包封于由1,3-丙二醇、卵磷脂和胆甾醇构成的脂质体内,形成的微型球状载体,其中,脂溶性活性成分补骨脂酚可包裹在磷脂双分子层间,具有粒径为100-200nm,粒径小,包封率可达90%以上,包封率高,载药量为3-8%,载药量大,可变形性和性质稳定等优点,能有效携带补骨脂酚有效成分通过角质层,达到基底层和真皮层,具有控油、抗皱、平滑肌肤、提亮肤色的效果。
本发明还从多方面提高补骨脂酚脂质体的透皮吸收效果:
其一,1,3-丙二醇本身是化妆品成分中常用的保湿剂,对肌肤具有保湿、润滑、促进吸收的功效;
其二,1,3-丙二醇与卵磷脂和胆甾醇形成脂质体,可以增加磷脂双分子层膜的流动性,使其易变性,提高了角质层分子的流动性,有助于透过角质层,提高吸收率;
其三,添加了乙酰化透明质酸钠,乙酰化透明质酸钠是透明质酸钠经乙酰化反应得到。乙酰化的透明质酸钠不只具有很好的亲水性,而且还具有很好的亲脂效果,在皮肤中存在形式为半镶嵌的结构,亲脂的一段可以牢牢附着在皮肤表皮上,在皮肤表面形成水合膜,增加角质层的水分,皮肤表皮在吸收一定量的水分后膨胀,进而降低皮肤结构的致密性,从而改变皮肤角质层的渗透性,促进补骨脂酚脂质体中的有效成分向皮肤渗透,在皮肤保湿性、皮肤修复性和增加皮肤弹性有着显著的效果。
其四,乙酰化透明质酸钠还可以通过疏水结构基团、共价结构基团等与磷脂相互作用,形成复合物,降低粘度,增强补骨脂酚脂质体的透皮吸收性,有效增加补骨脂酚透皮深度,提高活性物透皮吸收的能力,改善吸收效果。
因此,本发明制备得到的补骨脂酚脂质体载药量高,可达8%,粒径均匀,在100-200nm之间,稳定性好,乙酰化透明质酸钠和1,3-丙二醇,相辅相成,共同增加补骨脂酚脂质体的透皮吸收效果。
具体实施方式
下面结合实施例对本发明作进一步的说明,但并不作为对本发明限制的依据。
实施例:
一种含补骨脂酚的脂质体,其制备方法包括包括包括以下步骤:
步骤一、称取5份补骨脂酚、5份卵磷脂和1份胆甾醇加入到10份的辛酸/癸酸甘油三酯和20份的1,3-丙二醇中,于70℃下搅拌融解,得油相;其中卵磷脂中的磷脂酰胆碱的含量为70%;
步骤二、称取2份乙酰化透明质酸钠,加入到57份的水中,于70℃下搅拌溶解,得水相;
步骤三、将油相加入水相中,搅拌30min,得到初步混合液,然后使用高压均质机将初步混合液在1000bar的条件下均质循环5次,即得含补骨脂酚的脂质体。
其中补骨脂酚可以选择:补骨脂酚的CAS为10309-37-2,为淡黄色油状液体,纯度为99%。
补骨脂酚还可以按照以下方法进行提取得到的:
A、将补骨脂/补骨脂籽于-10~-5℃下低温冷冻,然后于-5~5℃下低温粉碎,得粒径为0.5-1um的A品;
B、将A品置于浓度为80-90%的乙醇溶液提取2-3次,每次5-6h,过滤得滤液和滤渣,合并滤液,回收溶剂,得B品;
C、合并滤渣,将滤渣经石油醚提取2-3次,每次5-6h,过滤,合并滤液,回收溶剂后,得C品;
D、将B品和C品混合,减压浓缩,静置后,得D品;
E、将D品与浓度为2%的氢氧化钠溶液混合,调节PH为10,静置,固液分离,得沉淀E品;
F、将沉淀E品经浓度为2%的氢氧化钠溶液溶解,然后经大孔吸附树脂处理,处理后,分别用水以及体积比为15:1的石油醚-乙酸乙酯冲洗3BV,去除水洗液液,回收油醚-乙酸乙酯洗脱液,减压浓缩,得成品。
提取方法能源消耗少,更好地保存补骨脂酚中的活性物质,去除补骨脂素和异补骨脂素,富集补骨脂酚,补骨脂酚的提取效率高,补骨脂酚中的活性纯度大于99%。
对上述的含补骨脂酚的脂质体,进行检测:
1)载药量:检测得到补骨脂酚脂质体的载药量为8%。
2)粒径分布和PDI:用激光粒度仪测定制备得到的脂质体的粒径分布和PDI,测得脂质体的粒径为100-200nm,PDI为0.18-0.26,温度为4℃下放置30后,粒径为120-220nm,PDI为0.19-0.28,因此制备所得的含补骨脂酚的脂质体,粒径小、均匀,稳定性好,提高吸收率。
3)体外透皮实验:
用剃刀将大鼠背部表面的毛发刮除,并通过手术将皮肤全层去除。用异丙醇擦拭真皮侧,清除残留的粘着的皮下脂肪,随后用PBS(pH=7.4)反复冲洗皮肤,用铝箔包好,-20℃保存备用。将老鼠皮肤固定在Franz扩散池上,有效渗透面积为1.766cm2,接收池中注入15mLPBS缓冲液,水浴温度37摄氏度。分别取不含乙酰化含透明质酸钠的补骨脂酚脂质体和含有乙酰化含透明质酸钠的补骨脂酚脂质体0.01mL于扩散池,密封。开启磁力搅拌器时计时,分别于不同时间点取样1.5mL。取样后,及时补充等体积的恒温PBS液。样品以12000r/min离心10min后,取上清液,测定样品中补骨脂酚的浓度C,然后计算累积透过量。
24h不含乙酰化含透明质酸钠的补骨脂酚脂质体的累积透过量:120μg/cm2;24h含有乙酰化含透明质酸钠的补骨脂酚脂质体的累积透过量:227μg/cm2。
由此可知,补骨脂酚脂质体中加入乙酰化透明质酸钠,吸收透过率更好。
Claims (5)
1.一种含补骨脂酚的脂质体,其特征在于:包括以下重量份数的原料:补骨脂酚3-8份、卵磷脂3-8份、胆甾醇0.5-1.5份、辛酸/癸酸甘油三酯5-15份、1,3-丙二醇15-30份、乙酰化透明质酸钠1-3份和水50-65份。
2.根据权利要求1所述的一种含补骨脂酚的脂质体,其特征在于:包括以下重量份数的原料:补骨脂酚5份、卵磷脂5份、胆甾醇1份、辛酸/癸酸甘油三酯10份、1,3-丙二醇20份、乙酰化透明质酸钠2份和水57份。
3.根据权利要求1所述的一种含补骨脂酚的脂质体,其特征在于:所述卵磷脂中磷脂酰胆碱的含量在70%以上。
4.根据权利要求1-3任意一项权利要求所述的含补骨脂酚的脂质体的制备方法,其特征在于:包括以下步骤:
步骤一、称取补骨脂酚、卵磷脂和胆甾醇加入到辛酸/癸酸甘油三酯和1,3-丙二醇中,于60-80℃下搅拌融解,得油相;
步骤二、称取乙酰化透明质酸钠,加入水中,于60-80℃下搅拌溶解,得水相;
步骤三、将油相加入水相中,搅拌20-40min,得到初步混合液,将初步混合液通过高压均质机在500-1500bar下均质循环3-8次,得含补骨脂酚的脂质体。
5.根据权利要求4所述的制备方法,其特征在于:包括以下步骤:
步骤一、称取补骨脂酚、卵磷脂和胆甾醇加入到辛酸/癸酸甘油三酯和1,3-丙二醇中,于70℃下搅拌融解,得油相;
步骤二、称取乙酰化透明质酸钠,加入水中,于70℃下搅拌溶解,得水相;
步骤三、将油相加入水相中,搅拌30min,得到初步混合液,将初步混合液用高压均质机在1000bar的条件下均质循环5次,得含补骨脂酚的脂质体。
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114028261A (zh) * | 2021-11-26 | 2022-02-11 | 浙江宜格企业管理集团有限公司 | 一种高神经酰胺负载量的柔性脂质体及其制备方法 |
CN114099440A (zh) * | 2021-12-08 | 2022-03-01 | 中国药科大学 | 一种装载疏水性抗氧化药物的传递体局部药物递送系统 |
CN115737515A (zh) * | 2022-11-23 | 2023-03-07 | 四川肽美生物科技有限公司 | 玻色因补骨脂酚皮肤抗衰老组合物及生产工艺 |
CN116585225A (zh) * | 2023-04-20 | 2023-08-15 | 杭州未可品牌管理有限公司 | 一种补骨脂酚微纳米乳液及其制备方法和用途 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101874763A (zh) * | 2009-04-29 | 2010-11-03 | 上海家化联合股份有限公司 | 一种白藜芦醇柔性脂质体及其制备方法 |
CN110392565A (zh) * | 2017-03-10 | 2019-10-29 | 奇华顿股份有限公司 | 有机化合物中或与之相关的改进 |
-
2021
- 2021-06-21 CN CN202110684230.4A patent/CN113509442A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101874763A (zh) * | 2009-04-29 | 2010-11-03 | 上海家化联合股份有限公司 | 一种白藜芦醇柔性脂质体及其制备方法 |
CN110392565A (zh) * | 2017-03-10 | 2019-10-29 | 奇华顿股份有限公司 | 有机化合物中或与之相关的改进 |
Non-Patent Citations (3)
Title |
---|
YOUNG HO CHO ETAL.: "Bioavailability Enhancement System for the Skin Permeation Promotion of Psolarea corylifolia Extract", 《KOREAN SOCIETY FOR BIOTECHNOLOGY AND BIOENGINEERING JOURNAL》 * |
YOUNG HO CHO ETAL.: "Development of Bioavailability Enhancement System for the Skin Permeation Promotion of Psolarea corylifolia Extract" * |
任姝静等: "有效浸润、多维促渗——功能多样的透明质酸" * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114028261A (zh) * | 2021-11-26 | 2022-02-11 | 浙江宜格企业管理集团有限公司 | 一种高神经酰胺负载量的柔性脂质体及其制备方法 |
CN114099440A (zh) * | 2021-12-08 | 2022-03-01 | 中国药科大学 | 一种装载疏水性抗氧化药物的传递体局部药物递送系统 |
CN115737515A (zh) * | 2022-11-23 | 2023-03-07 | 四川肽美生物科技有限公司 | 玻色因补骨脂酚皮肤抗衰老组合物及生产工艺 |
CN116585225A (zh) * | 2023-04-20 | 2023-08-15 | 杭州未可品牌管理有限公司 | 一种补骨脂酚微纳米乳液及其制备方法和用途 |
CN116585225B (zh) * | 2023-04-20 | 2023-12-12 | 杭州未可品牌管理有限公司 | 一种补骨脂酚微纳米乳液及其制备方法和用途 |
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