CN1478474A - 水飞蓟素自乳化微乳组合物及其制备工艺 - Google Patents

水飞蓟素自乳化微乳组合物及其制备工艺 Download PDF

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CN1478474A
CN1478474A CNA031343716A CN03134371A CN1478474A CN 1478474 A CN1478474 A CN 1478474A CN A031343716 A CNA031343716 A CN A031343716A CN 03134371 A CN03134371 A CN 03134371A CN 1478474 A CN1478474 A CN 1478474A
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silymarin
self
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CN1233317C (zh
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艳 刘
刘艳
李晓燕
李馨儒
赵振伟
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XI'AN LIJUN PHARMACEUTICAL CO Ltd
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Abstract

本发明涉及一种水飞蓟素自乳化微乳组合物及其制备工艺。本发明可使水飞蓟素的粒径达到纳米级，提高水飞蓟素的溶解度，提高吸收度。水飞蓟素自乳化微乳组合物，包括水飞蓟素、亚油酸乙酯、氢化蓖麻油和无水乙醇。本发明微乳体系的表面张力较单纯外相水的表面张力小，且各微乳体系均大大提高了水飞蓟素的溶解度。由扫描电镜可知，微乳粒子呈球形或近球形，粒径分布显示多数集中在10～50纳米，平均粒径17.2纳米。

Description

水飞蓟素自乳化微乳组合物及其制备工艺
技术领域
本发明涉及一种水飞蓟素自乳化微乳组合物及其制备工艺。
背景技术
水飞蓟素是从菊科植物水飞蓟果实中提取分离而得到的一类黄酮类化合物的总称。药理和毒理研究表明，水飞蓟素具有明显的保护肝细胞和稳定肝细胞的作用，临床上主要用于急慢性肝炎的治疗。但水飞蓟素难溶于水，生物利用度不好，导致疗效降低。韩国专利“水飞蓟素的口服微乳组合物”申请号为008013195，公开号为CN1316898A，提出可得到粒径1微米以下的微乳，但根据物理化学和药剂学的教科书中关于微乳的描述，微乳粒径为10～100纳米的乳滴分散在另一种液体中形成的胶体分散体系，外观透明，大小均匀，因此，上述发明并不能称为微乳。
发明内容
本发明的目的是提供一种水飞蓟素自乳化微乳组合物，本发明可使水飞蓟素的粒径达到纳米级，提高水飞蓟素的溶解度，提高吸收度。
水飞蓟素自乳化微乳组合物，包括水飞蓟素、亚油酸乙酯、氢化蓖麻油和无水乙醇，其配比为1～2∶1.2～2.4∶3.75～5∶2.5～7.5。
水飞蓟素自乳化微乳组合物的制备工艺，氢化蓖麻油和无水乙醇混合均匀，加入亚油酸乙酯超声振荡形成空白微乳浓缩液，加入水飞蓟素，室温磁力搅拌至全溶的水飞蓟素微乳浓缩液。
下表为7个水飞蓟微乳体系的理化性质考察
试验序号 表面张力(10-2J/m2) 溶解度(mg/ml)
    I     3.144     4.3136
    II     1.931     2.2386
    III     0.314     2.1949
    IV     1.572     2.2495
    V     1.437     2.2386
    VI     0.606     2.2495
    VII     3.860     2.7849
    水     7.253
上述各微乳体系的表面张力较单纯外相水的表面张力小，且各微乳体系均大大提高了水飞蓟素的溶解度。由扫描电镜可知，微乳粒子呈球形或近球形，粒径分布显示多数集中在10～50纳米，平均粒径17.2纳米。
附图说明
图1为水飞蓟素微乳组合物透色电镜扫描图。
图2为水飞蓟素微乳组合物粒径分布图。
具体实施方式
本发明配比如下：
实施例1 实施例2 实施例3 实施例4
水飞蓟素 40毫克 80毫克 40毫克 80毫克
亚油酸乙酯 33毫克 66毫克 33毫克 66毫克
氢化蓖麻油 150毫克 300毫克 200毫克 400毫克
无水乙醇 150毫克 300毫克 100毫克 200毫克
将氢化蓖麻油和无水乙醇按配方量混合均匀，加入亚油酸乙酯超声振荡形成空白微乳浓缩液，加入配方量水飞蓟素，室温磁力搅拌至全溶的水飞蓟素微乳浓缩液。
水飞蓟素微乳的大鼠离体小肠吸收实验
表3水飞蓟素微乳的大鼠离体小肠吸收结果
取样时间(h) 水飞蓟素 酚红 供试液体积(ml)    剩余药量
吸收度 浓度(μg/ml) 吸收度 浓度(μg/ml)   (×105μg)
  循环前           A0        C0＝2.00          A0           C0＝20.06       V0＝50.00       X0＝1.00
0.0           0.185         1.90            0.145            19.34            51.86            0.98
0.5           0.165         1.68            0.168             22.48           45.11            0.78
1.0           0.144         1.45            0.173             23.16           44.06            0.69
1.5           0.152         1.54            0.181             24.25           42.30            0.73
2.0           0.131         1.31            0.180             24.11           42.70            0.65
2.5           0.131         1.31            0.180             24.11           42.70            0.65
3.0           0.114         1.12            0.187             25.07           41.28            0.60
3.5           0.109         1.07            0.196             26.03           41.31            0.60
4.0           0.096         0.93            0.216             29.03           37.07            0.52
4.5           0.085         0.81            0.208             27.94           38.39             0.50
由以上结果可得，水飞蓟素微乳4.5小时的总吸收率为49.0％
水飞蓟素溶液的大鼠离体小肠吸收实验
表4水飞蓟素溶液的大鼠离体小肠吸收结果
取样时间(h) 水飞蓟素 酚红 供试液体积(ml) 剩余药量
吸收度 浓度(μg/ml) 吸收度 浓度(μg/ml)   (×105μg)
  循环前          A0        C0＝2.00           A0          C0＝20.06         V0＝50.00        X0＝1.000.0            0.116        115.00           0.145             19.34               51.70           0.590.5            0.114        112.00           0.143             19.07               53.01           0.521.0            0.071        66.00            0.143             19.07               53.61           0.491.5            0.064        58.00            0.148             19.75               52.34           0.452.0            0.060        54.00            0.149             19.88               52.51           0.442.5            0.077        72.00            0.152             20.29               51.95           0.443.0            0.076        72.00            0.151             20.16               52.76           0.463.5            0.067        61.00            0.153             20.43               52.54           0.414.0            0.060        58.00            0.156             20.84               51.96           0.40
由以上结果可得，水飞蓟素溶液4.0小时的总吸收率为32.2％。
由大鼠离体小肠吸收结果可以看出，将水飞蓟素微乳化以后确实提高了水飞蓟素的吸收。
水飞蓟素自乳化微乳系统的药代动力学
采用HPLC法，测定两组Wistar大鼠分别灌胃给与受试制剂和参比制剂后不同时刻血浆中水飞蓟素的浓度。于大鼠灌胃给药前和给药后间隔一定时间于眼眶后静脉丛取血测定，结果表明，受试制剂的生物利用度显著高于参比制剂。结果见表5。
表5水飞蓟素自乳化微乳系统的药代动力学结果
Concentration                      C(mg/L)
  t(h)   0   0.5   1.0   1.5   4.0   8.0
  受试制剂   0   29.6   32.7   23.4   11.3   3.8
  参比制剂   0   4.1   6.0   3.5   1.9   0.7
综上所述，自乳化微乳系统是增溶水飞蓟素和提高水飞蓟素生物利用度的有效方法。

Claims (2)

1、水飞蓟素自乳化微乳组合物，包括水飞蓟素、亚油酸乙酯、氢化蓖麻油和无水乙醇，其配比为1～2∶1.2～2.4∶3.7 5～5∶2.5～7.5。
2、制备如权利要求1所述的水飞蓟素自乳化微乳组合物的工艺，其特征在于：氢化蓖麻油和无水乙醇混合均匀，加入亚油酸乙酯超声振荡形成空白微乳浓缩液，加入水飞蓟素，室温磁力搅拌至全溶的水飞蓟素微乳浓缩液。
CN 03134371 2003-07-07 2003-07-07 水飞蓟素自乳化微乳组合物及其制备工艺 Expired - Lifetime CN1233317C (zh)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006021160A1 (fr) * 2004-08-27 2006-03-02 Shijiazhuang Pharma. Group Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. Système de relargage de médicament auto-émulsifiant à base de butylbenzènephtaléine, méthode de préparation et applications d’un tel système
EP1682088A4 (en) * 2003-10-21 2010-02-24 Hanmi Pharm Ind Co Ltd ORAL MICROEMULSION COMPOSITION COMPRISING BIPHENYLDIMETHYLDICARBOXYLATE AND SILYBINE
CN101342167B (zh) * 2007-07-10 2012-03-21 陈亚玲 药物组合物
CN115624526A (zh) * 2022-10-19 2023-01-20 江苏集萃新型药物制剂技术研究所有限公司 降脂保肝的双相组合物

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CN102488323A (zh) * 2011-12-13 2012-06-13 云南瑞升烟草技术（集团）有限公司 烟草净油乳化制剂及其在烟叶上的应用

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1682088A4 (en) * 2003-10-21 2010-02-24 Hanmi Pharm Ind Co Ltd ORAL MICROEMULSION COMPOSITION COMPRISING BIPHENYLDIMETHYLDICARBOXYLATE AND SILYBINE
WO2006021160A1 (fr) * 2004-08-27 2006-03-02 Shijiazhuang Pharma. Group Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. Système de relargage de médicament auto-émulsifiant à base de butylbenzènephtaléine, méthode de préparation et applications d’un tel système
AU2005276811B2 (en) * 2004-08-27 2008-11-13 Shijiazhuang Pharma. Group Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. Butylphthalide self-emulsifying drug delivery system, its preparation method and application
AU2005276811B8 (en) * 2004-08-27 2009-01-22 Shijiazhuang Pharma. Group Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. Butylphthalide self-emulsifying drug delivery system, its preparation method and application
US8728518B2 (en) 2004-08-27 2014-05-20 Cspc Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd Butylphthalide self-emulsifying drug delivery system, its preparation and method and application
CN101342167B (zh) * 2007-07-10 2012-03-21 陈亚玲 药物组合物
CN115624526A (zh) * 2022-10-19 2023-01-20 江苏集萃新型药物制剂技术研究所有限公司 降脂保肝的双相组合物

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