CN107375219B - 一种丹参酮ⅱa-羟基磷灰石固体分散体及其制备方法 - Google Patents

一种丹参酮ⅱa-羟基磷灰石固体分散体及其制备方法 Download PDF

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CN107375219B
CN107375219B CN201710809951.7A CN201710809951A CN107375219B CN 107375219 B CN107375219 B CN 107375219B CN 201710809951 A CN201710809951 A CN 201710809951A CN 107375219 B CN107375219 B CN 107375219B
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张丹丹
杨勇
张似锦
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Fengjie County People's Hospital
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Abstract

本发明涉及一种丹参酮ⅡA‑羟基磷灰石固体分散体及其制备方法，该丹参酮ⅡA‑羟基磷灰石固体分散体以丹参酮ⅡA为活性成分，以羟基磷灰石为固体载体，羟基磷灰石优选纳米羟基磷灰石，型号优选MH‑HAP04‑20。固体分散体中，所述丹参酮ⅡA与纳米羟基磷灰石的质量比为1:(6‑10)。该固体分散体的制备方法为：按质量比称取丹参酮ⅡA、羟基磷灰石用95％乙醇超声溶解或分散均匀，进行喷雾冷冻干燥。本发明提供的丹参酮ⅡA固体分散体以羟基磷灰石为固体载体，羟基磷灰石不仅可以提高丹参酮ⅡA在水中的溶解度，而且可以提高丹参酮ⅡA的光稳定性和热稳定性。

Description

一种丹参酮ⅡA-羟基磷灰石固体分散体及其制备方法
技术领域
本发明涉及药物制剂领域，尤其涉及一种丹参酮ⅡA固体分散体及其制备方法。
背景技术
丹参酮ⅡA是中药丹参中提取出来的活性成份，它是丹参原植物中含量最高的脂溶性成份。研究表明，丹参酮ⅡA具有多种药理作用。但是丹参酮ⅡA水溶性差，生物利用度低，而且光稳定性和热稳定性差(丹参酮ⅡA的化学稳定性研究，中药材，2010年第33卷4期)。
有研究者将丹参酮ⅡA采用水溶性载体制成固体分散体，虽然解决了丹参酮ⅡA的水溶性差的问题，但是光稳定性和热稳定性差依然难以有效解决(丹参酮ⅡA聚乙烯吡咯烷酮K30固体分散体的稳定性考察，中国药房，2008年第19卷第18期)。
因此，申请人在开发丹参酮ⅡA相关制剂时，需要在提高丹参酮ⅡA水溶性的同时提高丹参酮ⅡA的光稳定性和热稳定性。
发明内容
本发明目的在于提供一种丹参酮ⅡA固体分散体及制备方法，一方面提高丹参酮ⅡA的水溶性，另一方面提高丹参酮ⅡA的光稳定性和热稳定性差。
为实现上述目的，本发明提供了以下技术方案：
一种丹参酮ⅡA固体分散体，固体载体为纳米羟基磷灰石。
优选地，所述丹参酮ⅡA与纳米羟基磷灰石的质量比为1:(6-10)。
优选地，所述纳米羟基磷灰石的型号为MH-HAP04-20。
上述丹参酮ⅡA固体分散体的制备方法：按质量比称取丹参酮ⅡA、羟基磷灰石用95％乙醇超声溶解或分散均匀，进行喷雾冷冻干燥。
优选地，丹参酮ⅡA的质量浓度为8-12mg/mL。
优选地，所述喷雾冷冻干燥的有关参数为：压缩氮气压力为0.03-0.05MPa，料液流速10-15mL/min，冰箱温度最低达-110℃。
羟基磷灰石作为制剂辅料在提高丹参酮ⅡA水溶性、光和热稳定性方面的应用。
本发明的优点：
本发明提供的丹参酮ⅡA固体分散体以羟基磷灰石为固体载体，羟基磷灰石不仅可以提高丹参酮ⅡA在水中的溶解度，而且可以提高丹参酮ⅡA的光稳定性和热稳定性。
具体实施方式
实施例1丹参酮ⅡA-羟基磷灰石固体分散体的制备
按丹参酮ⅡA-羟基磷灰石质量比1:8称取丹参酮ⅡA、羟基磷灰石用95％乙醇超声溶解或分散均匀，进行喷雾冷冻干燥。其中，丹参酮ⅡA的质量浓度为10mg/mL，喷雾冷冻干燥的有关参数为：压缩氮气压力为0.04MPa，料液流速12mL/min，冰箱温度最低达-110℃。
羟基磷灰石的型号为MH-HAP04-20(纯度99％，针状，宽20nm，长150nm)，购自南京埃普瑞纳米材料有限公司。
实施例2丹参酮ⅡA-羟基磷灰石固体分散体的制备
按丹参酮ⅡA-羟基磷灰石质量比1:6称取丹参酮ⅡA、羟基磷灰石用95％乙醇超声溶解或分散均匀，进行喷雾冷冻干燥。其中，丹参酮ⅡA的质量浓度为8mg/mL，喷雾冷冻干燥的有关参数为：压缩氮气压力为0.04MPa，料液流速12mL/min，冰箱温度最低达-110℃。
羟基磷灰石的型号为MH-HAP04-20(纯度99％，针状，宽20nm，长150nm)，购自南京埃普瑞纳米材料有限公司。
实施例3丹参酮ⅡA-羟基磷灰石固体分散体的制备
按丹参酮ⅡA-羟基磷灰石质量比1:10称取丹参酮ⅡA、羟基磷灰石用95％乙醇超声溶解或分散均匀，进行喷雾冷冻干燥。其中，丹参酮ⅡA的质量浓度为12mg/mL，喷雾冷冻干燥的有关参数为：压缩氮气压力为0.04MPa，料液流速12mL/min，冰箱温度最低达-110℃。
羟基磷灰石的型号为MH-HAP04-20(纯度99％，针状，宽20nm，长150nm)，购自南京埃普瑞纳米材料有限公司。
实施例4效果实施例
1、溶解度水平的测定
按照《中国药典》2015版中溶解度水平的测定方法分别测定丹参酮ⅡA单体以及实施例1-3制备的固体分散体中丹参酮ⅡA在水中的溶解度水平。结果丹参酮ⅡA单体为微溶，实施例1-3制备的固体分散体中丹参酮ⅡA在水中为可溶，说明将丹参酮ⅡA制成固体分散体可显著提高其在水中溶解度，水溶性增强。
2、温度对丹参酮ⅡA单体及实施例1-3制备的固体分散体中丹参酮ⅡA稳定性的影响
将丹参酮ⅡA单体及实施例1-3制备的固体分散体粉末平铺于培养皿中，样品厚度约1mm，置于药物稳定性试验仪中，于80℃下放置10d，进行影响因素试验。在第0、5、10天末各取样1次，测定丹参酮ⅡA的含量并计算第5、10天末相对于0天的降解率(％)。
测定及计算结果如表1所示。
表1温度对丹参酮ⅡA稳定性的影响
丹参酮ⅡA单体 实施例1 实施例2 实施例3
5天末相对降解率(％) 26 ＜5 ＜5 ＜5
10天末相对降解率(％) 45 ＜5 ＜5 ＜5
3、光照对丹参酮ⅡA单体及实施例1-3制备的固体分散体中丹参酮ⅡA稳定性的影响
在温度25℃条件下，将将丹参酮ⅡA单体及实施例1-3制备的固体分散体粉末平铺于培养皿中，厚度约1mm，置于药物稳定性试验仪中，于光照度为(4500±500)Lx条件下放置10d，进行影响因素试验。在第0、5、10天末各取样1次，测定丹参酮ⅡA的含量并计算第5、10天末相对于0天的降解率(％)。
测定及计算结果如表2所示。
表2光照对丹参酮ⅡA稳定性的影响
丹参酮ⅡA单体 实施例1 实施例2 实施例3
5天末相对降解率(％) 53 ＜5 ＜5 ＜5
10天末相对降解率(％) 71 ＜5 ＜5 ＜5
本发明提供的丹参酮ⅡA固体分散体以羟基磷灰石为固体载体，羟基磷灰石不仅可以提高丹参酮ⅡA在水中的溶解度，而且可以提高丹参酮ⅡA的光稳定性和热稳定性。
本领域技术人员应当知道，上述具体实施方式仅用于解释本发明，本发明的保护范围并不局限于上述具体实施方式。

Claims (1)

1.型号为MH-HAP04-20的纳米羟基磷灰石作为制剂辅料在提高丹参酮ⅡA光稳定性方面的应用，其特征在于：所述制剂为由型号为MH-HAP04-20的纳米羟基磷灰石和丹参酮ⅡA组成的固体分散体。
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101057839A (zh) * 2005-04-12 2007-10-24 四川大学 丹参酮固体分散体及其用途
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CN101057839A (zh) * 2005-04-12 2007-10-24 四川大学 丹参酮固体分散体及其用途
CN102083467A (zh) * 2008-03-11 2011-06-01 Aska制药株式会社 固体分散体及其药物组合物、以及它们的制备方法
CN102793673A (zh) * 2012-09-07 2012-11-28 中国药科大学 一种小檗碱磷脂复合物固体分散体及其制备方法

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