CN114099438A - 山萘酚脂质体凝胶及其制备方法 - Google Patents
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Abstract
本发明公开了一种山萘酚脂质体凝胶及其制备方法。山萘酚脂质体凝胶包含如下重量份：山萘酚1～5％，大豆卵磷脂10～50％，胆固醇1～10％，卡波姆0.5～5％，甘油5～30％，丙二醇5～20％，三乙醇胺1～5％。山萘酚脂质体凝胶制备方法为：将山萘酚包裹进脂质体中，将脂质体分散在凝胶中，提高脂质体的稳定性及黏性，并有较好的生物相容性。本发明的山萘酚脂质体生产过程稳定，粒径及包封率较为理想，稳定性良好；所制备的山萘酚脂质体凝胶黏度适中，易于涂抹。
Description
技术领域
本发明属于药物制剂领域，具体涉及一种山萘酚脂质体、凝胶及其制备方法。
背景技术
山萘酚又称山萘黄素、5,7-三羟基黄酮醇，主要来源于姜科植物山柰的根茎，化学式为C15H10O6，属于黄酮类化合物，单体纯品为黄色结晶状粉末，微溶于水，溶于热乙醇、***和DMSO等有机溶剂。其广泛存在于各种水果、蔬菜及饮料中，人们已经从茶叶、椰菜、巫榛子、蜂胶、柚子以及其他绿色植物提取到它的纯品。因其具有防癌、抗癌、抗炎、抗氧化、抗菌、抗病毒等多种功效而受到人们的广泛关注。
山萘酚可通过不同的作用机制，如调控环氧合酶-2的转录、抑制P-糖蛋白的功能和表达、抑制白介素-4抗细胞增殖等，对胃癌细胞、肺癌细胞、肝癌细胞等多种肿瘤细胞起抑制作用或诱导细胞凋亡；山萘酚具有抑制AGE形成和消除自由基功能的作用，有较强的抗氧化作用。此外，有研究表明山萘酚还具有抗炎、抗菌作用，可用于治疗面部痤疮、炎症等，但目前对山萘酚的经皮研究较少。
脂质体是一种由磷脂双分子层作为膜材形成的一种类脂囊泡，既可以包裹亲脂性药物也可以包裹亲水性药物。类脂囊泡的类生物膜结构使得脂质体与人体皮肤具有较好的生物相容性，提高了药物的经皮透过率，降低毒副作用。
脂质体作为一种混悬溶液在储存过程中容易出现聚集、沉降等稳定性问题，将脂质体制备成凝胶剂，改善脂质体溶液不好保存的缺点，可以延长药物在皮肤表面的滞留时间达到缓释效果，提高药物在皮肤中的渗透量，同时可以使药物在凝胶中均匀分散。
发明内容：
本发明的目的之一是提供一种山萘酚脂质体凝胶及其制备方法，以满足山萘酚经皮给药的目的。
为了实现上述目的以及其他相关目的，本发明采用如下技术方案：
一种山萘酚脂质体溶液，由如下重量比成分组成：
优选地，所述山萘酚脂质体溶液由如下重量比成分组成：
更优选地，所述山萘酚脂质体溶液由如下重量比成分组成：
本发明的第二目的在于提供一种山萘酚脂质体溶液的制备方法，包括如下步骤：
(1)称取组分量山萘酚、胆固醇、大豆卵磷脂，于有机溶剂中溶解；
(2)将溶液置于圆底烧瓶中，水浴加热溶解，以薄膜分散法，将圆底烧瓶置于旋转蒸发仪上水浴减压蒸干有机溶剂，加pH为7.4的磷酸盐缓冲液水化；
(3)将脂质体溶液置于烧杯中，冰浴条件下超声，即得山萘酚脂质体溶液。优选地，所述有机溶剂加入量为1～20％，有机溶液为甲醇、乙醇或氯仿，更优选乙醇；水浴加热温度为35～60℃；超声功率为100～200w，超声时间为 5～20min。
本发明的最终目的在于提供一种山萘酚脂质体凝胶，由如下重量比成分组成：
优选地，所述山萘酚脂质体凝胶由如下重量比成分组成：
本发明还有目的在于提供一种山萘酚脂质体凝胶的制备方法，包括如下步骤：
(1)称取组分量的卡波姆、甘油、丙二醇及水于烧杯中，搅拌均匀，使其充分溶胀，加三乙醇胺调节pH值得空白凝胶；
(2)将空白凝胶与山萘酚脂质体溶液混合并搅拌均匀，即得山萘酚脂质体凝胶。
优选地，所述调节pH值至6～8。
本发明积极效果是，脂质体由卵磷脂制备而成，具有类似于生物膜结构的双分子脂质层，中心亲水链部分可溶解亲水性药物，双层磷脂部分可溶解亲脂性药物，增加药物的溶解度。脂质体可以作为经皮给药的优良载体，但在临床使用中，液体制剂作为经皮给药不方便给药，限制了其在外用给药中的应用。凝胶基质可以增加脂质体的黏度，增加药物在皮肤表面的滞留时间，且亲水性凝胶具有适宜涂抹、易清洗、不污染衣物等优点。
本发明的山萘酚脂质体凝胶体外释药结果表明，相对于山萘酚普通凝胶，山萘酚脂质体凝胶有明显的缓释效果，并且24h离体皮肤累积透过量以及皮肤滞留量显著提高，说明与普通凝胶相比，脂质体凝胶更具有作为药物经皮吸收载体的优势。
下面结合实施例和说明书附图，对本发明做进一步详细说明。
附图说明
图1是本发明用HPLC法测定样品浓度所得释放曲线图。
图2是本发明用HPLC法测定单位累积透过量所得体外经皮渗透曲线图。
具体实施方式
实施例1山萘酚脂质体凝胶制备
分别称取山萘酚100mg、大豆卵磷脂3000mg及胆固醇500mg于圆底烧瓶中，加入20ml乙醇，置于500ml圆底烧瓶中，于旋转蒸发仪上，水浴 55℃旋转加热，蒸干乙醇后继续旋转10min，后加50ml磷酸盐缓冲液(pH7.4) 37℃下水化30min，后置于烧杯中，于冰浴条件下超声10min，即得浓度为 2mg/ml的山萘酚脂质体溶液。
包封率测定：取0.5ml脂质体溶液于透析袋中扎紧。将透析袋置于20ml 0.5％吐温-80溶液中，在37℃恒温水浴、转速100rpm·min-1条件下，在2， 4，6，8，10，12h取溶出介质2ml，同时补加2ml同温度的溶出介质。将样品过0.22μm滤膜，测定样品浓度CFree，同时测定脂质体溶液的总浓度CTotle。根据公式EE％＝(CTotle-CFree)/CTotle×100％计算山萘酚脂质体的包封率为 60.55％。
粒径和电位测定：取适量山萘酚脂质体溶液，用蒸馏水稀释，摇匀，采用激光动态散射法测定其粒径和ζ电位，山萘酚脂质体的粒径为164.3±6.0 nm，ζ电位为-46.40±2.44mV。
透射电镜观察：取适量山萘酚脂质体混悬液用蒸馏水稀释，用2％磷钨酸溶液负染，滴于铜网上，自然晾干，在透射电镜下观察，山萘酚脂质体呈均匀球形。
称取卡波姆400mg、甘油6000mg及丙二醇4000mg于烧杯中，加40ml 水搅拌均匀，放置过夜使其充分溶胀，后加入1200mg三乙醇胺调节pH值至 7，得空白凝胶。
将空白凝胶与山萘酚脂质体溶液混合并搅拌均匀，即得山萘酚脂质体凝胶。
实施例2山萘酚脂质体凝胶制备
分别称取山萘酚100mg、大豆卵磷脂2500mg及胆固醇600mg于圆底烧瓶中，加入30ml乙醇，置于500ml圆底烧瓶中，于旋转蒸发仪上，水浴 55℃旋转加热，蒸干乙醇后继续旋转10min，后加50ml磷酸盐缓冲液(pH7.4) 37℃下水化30min，后置于烧杯中，于冰浴条件下超声10min(超声功率为 110w)，即得浓度为2mg/ml的山萘酚脂质体溶液。山萘酚脂质体的包封率为 59.23％，粒径为160.3±4.3nm，ζ电位为-40.55±3.57mV，在透射电镜下观察，山萘酚脂质体呈均匀球形。
称取卡波姆400mg、甘油6000mg及丙二醇4000mg于烧杯中，加40ml 水搅拌均匀，放置过夜使其充分溶胀，后加入1200mg三乙醇胺调节pH值至 7，得空白凝胶。
将空白凝胶与山萘酚脂质体溶液混合并搅拌均匀，即得山萘酚脂质体凝胶。
实施例3山萘酚脂质体凝胶制备
分别称取山萘酚100mg、大豆卵磷脂3000mg及胆固醇500mg于圆底烧瓶中，加入20ml乙醇，置于500ml圆底烧瓶中，于旋转蒸发仪上，水浴 55℃旋转加热，蒸干乙醇后继续旋转10min，后加50ml磷酸盐缓冲液(pH7.4) 37℃下水化30min，后置于烧杯中，于冰浴条件下超声10min，即得浓度为 2mg/ml的山萘酚脂质体溶液。
称取卡波姆500mg、甘油6000mg及丙二醇6000mg于烧杯中，加40ml 水搅拌均匀，放置过夜使其充分溶胀，后加入1500mg三乙醇胺调节pH值至 7，得空白凝胶。
将空白凝胶与山萘酚脂质体溶液混合并搅拌均匀，即得山萘酚脂质体凝胶。
实施例4山萘酚脂质体凝胶与普通凝胶的体外释放试验
取山萘酚脂质体凝胶和山萘酚普通凝胶各2g分别放入透析袋中扎紧。将透析袋置于40ml 0.5％吐温-80溶液中，在37℃恒温水浴、转速100rpm·min-1条件下，在2，4，6，8，10，12h，24h取溶出介质2ml，同时补加2ml同温度的溶出介质。将样品过0.22μm滤膜，用HPLC法测定样品浓度。所得释放曲线如图1所示。
由图1可知，山萘酚普通凝胶快速释放，而山萘酚脂质体凝胶缓慢释放， 最终维持在一定的药物浓度，达到缓释效果，从而延长药物的作用时间，减 少给药次数。
实施例5山萘酚脂质体凝胶的体外透皮试验
采用Franz扩散池法，离体SD大鼠皮肤平铺于Franz立式扩散池上， 角质层面向上，固定好，接收液面与皮肤下方充分接触，无气泡。在供给池 上加入山萘酚脂质体凝胶1g(相当于含山萘酚5mg)及同等含药量的山萘酚 普通凝胶1g(制备方法与脂质体凝胶制备方法相同，只是将山萘酚脂质体溶 液替换为含相同药量的山萘酚水溶液)，将扩散池置于透皮扩散试验仪中， 32±0.5℃恒温水浴，400r·min-1转速搅拌，分别于1，2，4，6，8，10，12h取2ml接收液，并立刻补加同等温度的2ml接收液，将接收液过0.22μm滤 膜后用高效液相色谱法测定单位累积透过量。测定结果如图2所示，山萘酚 脂质体凝胶12h内单位累积透过量高于山萘酚普通凝胶。
离体透皮试验结束后，将皮肤取下剪碎，加入2ml甲醇，超声提取30min，取上清液过0.22μm滤膜后用高效液相色谱法测定药物含量。结果显示山萘酚脂质体凝胶在皮肤内的滞留量明显高于山萘酚普通凝胶。
以上实施例仅用以说明本发明的技术方案，而非对其限制。本领域的普通技术人员应当理解：其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换；而这些修改或者替换，并不使相应技术方案的本质脱离本发明各实施例技术方案的精神和范围。
Claims (9)
1.一种山萘酚脂质体溶液，其特征在于，包含以下重量比成分：
2.如权利要求1所述的山萘酚脂质体溶液，其特征在于，包含以下重量比成分：
3.如权利要求1所述的山萘酚脂质体溶液，其特征在于，包含以下重量比成分：
4.一种制备如权利要求1～3所述的山萘酚脂质体溶液制备方法，包括如下步骤：
(1)称取组分量山萘酚、胆固醇、大豆卵磷脂，于有机溶剂中溶解；
(2)将溶液置于圆底烧瓶中，水浴加热溶解，以薄膜分散法，将圆底烧瓶置于旋转蒸发仪上水浴减压蒸干有机溶剂，加pH为7.4的磷酸盐缓冲液水化；
(3)将脂质体溶液置于烧杯中，冰浴条件下超声，即得山萘酚脂质体溶液。
5.如权利要求4所述的山萘酚脂质体溶液制备方法，其特征在于：
步骤(1)中所述有机溶剂为甲醇、乙醇或氯仿，用量为1～20％；
步骤(2)中所述水浴加热温度为35～60℃；
步骤(3)中所述超声功率为100～200w，超声时间为5～20min。
6.一种山萘酚脂质体凝胶，其特征在于，由如下重量比成分组成：
7.如权利要求6所述的山萘酚脂质体凝胶，其特征在于，由如下重量比成分组成：
8.一种制备如权利要求6或7所述的山萘酚脂质体凝胶的制备方法，，包括如下步骤：
(1)称取处方量的卡波姆、甘油、丙二醇及水于烧杯中，搅拌均匀，使其充分溶胀，加三乙醇胺调节pH值得空白凝胶；
(2)将空白凝胶与山萘酚脂质体溶液混合并搅拌均匀，即得山萘酚脂质体凝胶。
9.如权利要求8所述的山萘酚脂质体凝胶的制备方法，其特征在于，使用三乙醇胺调节pH值至6～8。
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115487205A (zh) * | 2022-09-16 | 2022-12-20 | 中国计量大学 | 一种黑茶多糖-荷叶碱微凝胶复合物及其制备方法和应用 |
| CN116270425A (zh) * | 2023-01-18 | 2023-06-23 | 哈尔滨医科大学 | 用于治疗银屑病的含三氧化二砷纳米脂质体的长效凝胶制剂及其制备方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103622903A (zh) * | 2013-12-04 | 2014-03-12 | 山东大学 | 盐酸***脂质体凝胶及其制备方法 |
| CN104306368A (zh) * | 2014-10-09 | 2015-01-28 | 中国人民解放军第二军医大学 | 山奈酚在制备抗hcv感染药物中的应用 |
| CN105982844A (zh) * | 2015-02-11 | 2016-10-05 | 中国人民解放军第二军医大学 | 一种白藜芦醇脂质体凝胶及其制备方法 |
| CN108464993A (zh) * | 2018-03-20 | 2018-08-31 | 陈锦珊 | 一种镰形棘豆总黄酮脂质体凝胶及其制备方法 |
-
2021
- 2021-11-11 CN CN202111333124.8A patent/CN114099438A/zh active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103622903A (zh) * | 2013-12-04 | 2014-03-12 | 山东大学 | 盐酸***脂质体凝胶及其制备方法 |
| CN104306368A (zh) * | 2014-10-09 | 2015-01-28 | 中国人民解放军第二军医大学 | 山奈酚在制备抗hcv感染药物中的应用 |
| CN105982844A (zh) * | 2015-02-11 | 2016-10-05 | 中国人民解放军第二军医大学 | 一种白藜芦醇脂质体凝胶及其制备方法 |
| CN108464993A (zh) * | 2018-03-20 | 2018-08-31 | 陈锦珊 | 一种镰形棘豆总黄酮脂质体凝胶及其制备方法 |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115487205A (zh) * | 2022-09-16 | 2022-12-20 | 中国计量大学 | 一种黑茶多糖-荷叶碱微凝胶复合物及其制备方法和应用 |
| CN115487205B (zh) * | 2022-09-16 | 2024-03-29 | 中国计量大学 | 一种黑茶多糖-荷叶碱微凝胶复合物及其制备方法和应用 |
| CN116270425A (zh) * | 2023-01-18 | 2023-06-23 | 哈尔滨医科大学 | 用于治疗银屑病的含三氧化二砷纳米脂质体的长效凝胶制剂及其制备方法 |
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