基于双位点同步微透析技术的青藤碱微乳凝胶皮肤及血液药代动力学研究

丁杨; 钱珊珊; 郭健; 桂双英

doi:10.14148/j.issn.1672-0482.2022.1050

基于双位点同步微透析技术的青藤碱微乳凝胶皮肤及血液药代动力学研究

doi: 10.14148/j.issn.1672-0482.2022.1050

丁杨^{1, 2, 3, 4,},
钱珊珊⁵,
郭健^{1, 2, 3, 4},
桂双英^{1, 2, 3, 4, ,}

1.
安徽中医药大学药学院, 安徽合肥 230012
2.
安徽省中医药科学院药物制剂研究所, 安徽合肥 230012
3.
现代药物制剂安徽省教育厅工程技术研究中心, 安徽合肥 230012
4.
药物制剂技术与应用安徽省重点实验室，安徽合肥 230012
5.
安徽中医药大学第二附属医院, 安徽合肥 230061

基金项目:

国家自然基金面上项目 81873019

安徽高校自然科学研究项目 KJ2021A0541

详细信息

作者简介:
丁杨，女, 讲师，E-mail：1332494359@qq.com

桂双英，教授，博士生导师, 国家一流课程《中药药剂学>课程负责人，安徽省药剂学重点学科带头人, 安徽省高校领军人才团队带头人、安徽省学术与技术带头人、药物制剂技术与应用安徽省重点实验室主任、安徽省中医药科学院药物制剂研究所所长。兼任世中联经皮给药专委会副会长、中国中药协会精准中药专业委员会副主任委员等。主持国家自然科学基金区域联合基金、面上项目等省部级以上科研项目22项，以第一完成人获安徽省科技进步一等奖、中国产学研合作研究会创新成果二等奖各1项，参与获中华中医药学会一等奖等省级以上科技奖励5项。主持获安徽省教学成果一、二等奖各1项

通讯作者:
桂双英, 女，教授，主要从事制剂新制剂与新技术的研究，E-mail：guishy0520@126.com

中图分类号: R283
计量
- 文章访问数: 150
- HTML全文浏览量: 12
- PDF下载量: 25
- 被引次数: 0
出版历程
- 收稿日期: 2022-08-15
- 网络出版日期: 2022-11-19
- 发布日期: 2022-11-10

Pharmacokinetic Study of Skin and Blood of Sinomenine-Loaded Microemulsion Gel Based on Double Sites Simultaneous Microdialysis

DING Yang^{1, 2, 3, 4
,},
QIAN Shan-shan⁵,
GUO Jian^{1, 2, 3, 4},
GUI Shuang-ying^{1, 2, 3, 4
, ,}

1.
College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China
2.
Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei 230012, China
3.
Engineering Technology Research Center of Modernized Pharmaceutics Anhui Education Department, Hefei 230012, China
4.
Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Hefei 230012, China
5.
The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230061, China

摘要

摘要: 目的采用双位点同步微透析技术研究青藤碱微乳凝胶(Sinomenine-loaded microemulsion gel, SMG)的大鼠皮肤与血液药代动力学过程, 探究SMG的经皮药代动力学特征。方法建立青藤碱的超高液相色谱(UPLC)含量测定方法, 开展专属性、线性、精密度、回收率等方法学考察。SD大鼠经麻醉, 腹部脱毛处理后, 植入线性探针和血液探针, 局部涂抹青藤碱微乳凝胶, 采用微透析技术结合UPLC技术测定皮肤和血液透析液中青藤碱浓度。结果青藤碱的UPLC分析方法在0.5~20 μg·mL^-1浓度范围内线性良好, 色谱的专属性、精密度及回收率等均符合微透析样品检测要求。药代动力学研究中青藤碱在皮肤中C_max为(10.91±3.05)μg·mL^-1, T_max为(180.00±39.80)min, AUC_0→t为(736.51±45.30)μg·min·mL^-1; 在血液中C_max为(6.74±1.91)μg·mL^-1, T_max为(239.98±40.85)min, AUC_0→t为(426.43±30.18)μg·min·mL^-1。结论 SMG经皮给药后能够缓慢持续释放青藤碱, 可在皮肤中形成储库效应。
- 经皮给药 /
- 青藤碱 /
- 微乳凝胶 /
- 微透析 /
- 探针 /
- 经皮药代动力学
Abstract: OBJECTIVE To investigate the pharmacokinetics of sinomenine-loaded microemulsion gel (SMG) by skin and blood microdialysis in rats, and explore the pharmacokinetic characteristics of SMG. METHODS An UPLC method for the determination of sinomenine was established, and its specificity, linearity, precision and recovery rate were examined. The probe was implanted after the rats were anesthetized and depilated, then the sinomenine microemulsion gel was applied onto the bare abdominal skin of the rats. The microdialysis technique and UPLC were used to determine the concentration of the drug. RESULTS The results showed that the established method for the determination of sinomenine microemulsion gel was well linear in the range of 0.5-20 μg·mL^-1, and the specificity, degree of precision and recovery rate of the chromatography all conformed to the examination requirements of microdialysis samples.The results of pharmacokinetic study showed that the C_max values of sinomenine in skin and blood were (10.91±3.05) and (6.74±1.91)μg·mL^-1, respectively. The T_max values were (180.00±39.80) and (239.98±40.85)min, respectively. And the AUC_0→t values were (736.51±45.30) and (426.43±30.18)μg·min·mL^-1. CONCLUSION The sinomenine microemulsion gel plays a role in forming skin reservoir through percutaneous penetration, and can control the sustained release of drug.
- transdermal administration /
- sinomenine /
- microemulsion gel /
- microdialysis /
- probe /
- transdermal pharmacokinetics

HTML全文

图 1 专属性考察的UPLC色谱图

Figure 1. UPLC characteristic chromatograms of the exclusive investigation

下载: 全尺寸图片幻灯片

图 2 探针植入图

Figure 2. Probe implantation diagram

下载: 全尺寸图片幻灯片

图 3 大鼠皮肤和血液青藤碱浓度-时间曲线(x±s，n=5)

Figure 3. Mean subcutaneous concentration-time profiles of sinomenine in the skin and blood (x±s, n=5)

下载: 全尺寸图片幻灯片

表 1 青藤碱皮肤和血液主要药代动力学参数

Table 1. Main pharmacokinetic parameters of sinomenine in the skin and blood

参数	皮肤	血液
t_1/2Kα/min	99.85±16.90	113.76±26.61
t_1/2Ke/min	122.13±21.72	161.65±20.33
T_max/min	180.00±39.80	239.98±40.85
C_max/μg·mL^-1	10.91±3.05	6.74±1.91
AUC_0→t/(μg·min·mL^-1)	736.51±45.30	426.43±30.18

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