基于微透析结合UPLC的弩药微乳经皮给药后多成分皮肤药动学研究

谢欢; 宋选飞; 周斌; 刘耀; 杨芳芳; 陈迎龙; 朱艳; 张永萍

doi:10.14148/j.issn.1672-0482.2024.0167

基于微透析结合UPLC的弩药微乳经皮给药后多成分皮肤药动学研究

doi: 10.14148/j.issn.1672-0482.2024.0167

谢欢^1,,
宋选飞¹,
周斌¹,
刘耀^{1, 2, 3},
杨芳芳^{1, 2, 3},
陈迎龙⁴,
朱艳⁵,
张永萍^{1, 2, 3, ,}

1.
贵州中医药大学药学院, 贵州贵阳 550025
2.
贵州省中药民族药炮制与制剂工程技术研究中心, 贵州贵阳 550025
3.
国家苗药工程技术研究中心, 贵州贵阳 550025
4.
贵州中医药大学针灸推拿学院，贵州贵阳 550025
5.
贵州健康职业学院中医药系，贵州铜仁 554300

基金项目:

国家自然科学基金面上项目 82160753

贵州省高等学校中药民族药(苗药)新剂型新制剂工程研究中心项目黔教技〔2022〕022

国家苗药工程技术研究中心能力提升项目黔科合中引地〔2023〕006

详细信息

作者简介:
谢欢, 女, 硕士研究生，E-mail: 2591708814@qq.com

通讯作者:
张永萍, 女, 教授, 博士生导师，主要从事中药及民族药新制剂、新剂型与新技术开发研究，E-mail: zgygpg@126.com

中图分类号: 285.5
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- 文章访问数: 59
- HTML全文浏览量: 9
- PDF下载量: 2
- 被引次数: 0
出版历程
- 收稿日期: 2023-07-28
- 网络出版日期: 2024-02-26
- 发布日期: 2024-02-10

Study on the Multi-Component Skin Pharmacokinetics of Crossbow Microemulsion after Transdermal Administration Based on Microdialysis Combined with UPLC

XIE Huan^1
,,
SONG Xuanfei¹,
ZHOU Bin¹,
LIU Yao^{1, 2, 3},
YANG Fangfang^{1, 2, 3},
CHEN Yinglong⁴,
ZHU Yan⁵,
ZHANG Yongping^{1, 2, 3
, ,}

1.
School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
2.
Guizhou Institute of Engineering and Technology for Processing and Preparation of Traditional Chinese Medicine and Ethnic Medicine, Guiyang 550025, China
3.
National Engineering and Technology Research Center of Miao Medicine, Guiyang 550025, China
4.
College of Acupuncture and Tuina, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
5.
School of Traditional Chinese Medicine, Guizhou Health Vocation College, Tongren 554300, China

摘要

摘要: 目的考察弩药微乳多成分在家兔皮肤组织中的药动学特征。方法采用UPLC测定绿原酸、苯甲酰新乌头原碱、杠柳毒苷、新乌头碱质量浓度; 采用增量法与减量法探究温度、灌流速度、质量浓度对探针回收率的影响, UPLC测定弩药微乳经皮给药后不同时间点透析液中多成分含量变化, 并用DAS2.0软件处理数据。结果升高温度, 各成分探针回收率逐渐提高; 流速越大, 药物回收率越低, 且回收率与探针周围药物质量浓度关系不大。弩药微乳中绿原酸、苯甲酰新乌头原碱、杠柳毒苷、新乌头碱在皮下组织中的药动学参数C_max分别为(3.24±0.36)(1.04±0.29)(4.78±2.15)(2.86±0.55)μg·mL^-1; AUC_0-∞分别为(52.42±30.84)(7.70±3.73)(42.23±13.93)(22.68±12.51)h·μg·mL^-1。结论首次采用微透析在体实时取样技术, 建立UPLC检测方法, 对弩药微乳经皮给药后多成分皮肤药动学进行研究, 为弩药微乳后续的考察及应用提供参考。
- 弩药微乳 /
- 微透析 /
- UPLC /
- 皮肤药动学
Abstract: OBJECTIVE To investigate the pharmacokinetic characteristics of crossbow microemulsion in rabbit skin. METHODS The concentrations of chlorogenic acid, benzoyl new aconitine, periplocin and new aconitine were determined by UPLC. The effects of temperature, perfusion speed and mass concentration on the recovery rate of the probe were investigated by incremental and decrement methods, the changes of multi-component content in the dialysate at different time points after transdermal administration of crossbow microemulsion were determined by UPLC, and DAS 2.0 software was used to process the data. RESULTS The recovery rate of the probe increased with increasing temperature, and the higher the flow rate, the lower the recovery rate. The pharmacokinetic parameters of chlorogenic acid, benzoyl new aconitine, periplocin and new aconitine in microemulsion C_max were (3.24±0.39) (1.04±0.29) (4.78 ± 2.15) (2.86 ± 0.55) μg·mL^-1, respectively, and in AUC_0-∞ were (52.42 ± 30.84) (7.70 ± 3.73) (42.23 ± 13.93) (22.68 ± 12.51) h·mg·mL^-1, respectively. CONCLUSION A real-time in vivo microdialysis sampling technique was first used and a UPLC detection technique was established to study the skin pharmacokinetics of multi-components of crossbow microemulsion after transdermal administration, which provides a reference for the follow-up investigation and application of crossbow microemulsion.
- crossbow microemulsion /
- microdialysis /
- UPLC /
- skin pharmacokinetics

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图 1 混合对照品(a)、在体微透析样品(b)、空白灌流液(c)色谱图

注: 1. 绿原酸; 2. 苯甲酰新乌头原碱; 3. 杠柳毒苷; 4. 新乌头碱

Figure 1. Mixed control substance (a), in vivo microdialysis sample (b), blank perfusion (c) chromatograms

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图 2 不同温度下4种成分RR

Figure 2. RR of 4 components at different temperatures

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图 3 不同流速下4种成分RR及RL

Figure 3. RR and RL of 4 components at different flow velocities

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图 4 不同质量浓度下4种成分RR及RL

Figure 4. RR and RL of 4 components in different concentrations

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图 5 探针在体回收率(x±s，n=3)

Figure 5. In vivo recovery rate of the probe (x±s, n=3)

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图 6 弩药微乳经皮给药后皮下组织中4种成分药-时曲线图(x±s，n=3)

Figure 6. Drug-time curve of 4 components in subcutaneous tissue after transdermal administration of crossbow microemulsion (x±s, n=3)

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表 1 4种成分线性回归方程及线性范围

Table 1. 4 Linear regression equations and linear range

指标成分	回归方程	r	线性范围/(μg·mL^-1)
绿原酸	Y=8 519.9X+3 428.8	0.999 8	0.483~96.600
苯甲酰新乌头原碱	Y=5 935X+1 625.7	0.999 6	0.489~97.800
杠柳毒苷	Y=3 059.6X+87.918	0.999 8	0.529~105.800
新乌头碱	Y=6 181.3X+524.19	0.999 9	0.443~88.600

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表 2 4种成分线性回归方程及线性范围

Table 2. 4 Linear regression equations and linear range

指标成分	回归方程	r	线性范围/(μg·mL^-1)
绿原酸	Y=85 424X-1 641.8	0.999 9	0.122~12.240
苯甲酰新乌头原碱	Y=66 715X-262.06	0.999 9	0.018~6.670
杠柳毒苷	Y=28 799X+3 927.1	0.999 2	0.108~10.830
新乌头碱	Y=64 331X-77 487	1.000 0	0.097~9.770

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表 3 各成分药动学具体参数(x±s，n=3)

Table 3. Specific pharmacokinetic parameters of each component (x±s, n=3)

PK参数	绿原酸	苯甲酰新乌头原碱	杠柳毒苷	新乌头碱
t_max/h	5.01±0.00	3.33±2.08	5.67±1.53	4.67±0.56
C_max/μg·mL^-1	3.24±0.36	1.04±0.29	4.78±2.15	2.86±0.55
AUC_{0-11 h}/μg·mL^-1·h	23.28±2.23	5.92±1.65	31.98±16.51	16.95±4.34
AUC_0-∞/μg·mL^-1·h	52.42±30.84	7.70±3.73	42.23±13.93	22.68±12.51
MRT_{0-11 h}/h	5.53±0.41	5.33±0.82	6.13±0.89	5.31±0.30
MRT_0-∞/h	22.98±22.80	9.41±4.24	9.40±5.20	7.77±2.68

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