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1.承德医学院,河北 承德 067000
2.中国中医科学院 中药研究所,北京 100700
3.河北省中药新辅料技术创新中心,河北 承德 067000
4.深圳建安医药有限公司,广东 深圳 518000
王明硕,在读硕士,从事中药制剂研究,E-mail:13832412280@163.com
王春民,硕士,主任中药师,从事中药新技术与新应用研究,E-mail:13603140779@139.com; *
刘淑芝,研究员,博士生导师,从事中药新剂型与新药开发研究,E-mail:liushuzhi2004@sina.com
收稿日期:2021-10-21,
网络出版日期:2022-01-05,
纸质出版日期:2022-03-05
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王明硕,杜茂波,沈硕等.椒姜凝胶贴膏的体外释药动力学与药效学评价[J].中国实验方剂学杂志,2022,28(05):141-147.
WANG Ming-shuo,DU Mao-bo,SHEN Shuo,et al.In Vitro Pharmacokinetics and Pharmacodynamic Evaluation of Jiaojiang Cataplasms[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(05):141-147.
王明硕,杜茂波,沈硕等.椒姜凝胶贴膏的体外释药动力学与药效学评价[J].中国实验方剂学杂志,2022,28(05):141-147. DOI: 10.13422/j.cnki.syfjx.20220155.
WANG Ming-shuo,DU Mao-bo,SHEN Shuo,et al.In Vitro Pharmacokinetics and Pharmacodynamic Evaluation of Jiaojiang Cataplasms[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(05):141-147. DOI: 10.13422/j.cnki.syfjx.20220155.
目的
2
研究椒姜凝胶贴膏的体外动力学并对其药效学进行评价,为该制剂的开发提供可行性依据。
方法
2
采用改良的Franz扩散池法进行体外释放与透皮试验,分别以半透膜和离体小鼠皮肤作为透过屏障,采用高效液相色谱法(HPLC)测定指标成分羟基-
α
-山椒素、人参皂苷Rb
1
及6-姜辣素的含量,以评价椒姜凝胶贴膏的释放与经皮渗透效果。6-姜辣素和羟基-
α
-山椒素检测的流动相为水-乙腈-甲醇(2∶1∶1),检测波长280 nm;人参皂苷Rb
1
检测的流动相为乙腈-0.1%磷酸水溶液(31∶69),检测波长203 nm。建立小鼠肠麻痹模型,动物随机分为5组,即假手术组、模型组、多潘立酮组(3.9 mg·kg
-1
)及椒姜凝胶贴膏高、低剂量组(6.2,3.1 g·kg
-1
,以生药量计),观察椒姜凝胶贴膏对模型动物胃肠推进功能的影响。
结果
2
椒姜凝胶贴膏中羟基-
α
-山椒素,6-姜辣素及人参皂苷Rb
1
在24 h的平均释放速率分别为16.41,4.23,4.15 μg∙cm
-2
∙h
-1
;体外透皮试验中24 h平均透过速率分别为2.31,0.64,0.29 μg∙cm
-2
∙h
-1
;皮肤滞留量分别为19.56,3.59,1.61
μg。根据Ritger-Peppas方程,确定羟基-
α
-山椒素、人参皂苷Rb
1
及6-姜辣素的释放为非Fick扩散。椒姜凝胶贴膏高剂量组对模型小鼠小肠摩擦损伤术后的肠功能具有一定改善作用,可以促进肠蠕动,促进小肠推进率(
P
<
0.05)。
结论
2
椒姜凝胶贴膏具有体外释放和透皮性能,体外释放符合Higuchi方程,经皮渗透行为符合零级动力学方程,其对术后的小肠功能有改善作用,可提高小肠推进功能,初步说明该制剂具有一定的临床开发价值。
Objective
2
To study the
in vitro
kinetics of Jiaojiang cataplasms and evaluate its pharmacodynamics, so as to provide a feasible basis for the development of this preparation.
Method
2
The improved Franz diffusion cell was used for the
in vitro
release in semipermeable membrane and transdermal absorption in
in vitro
mouse skins. The contents of hydroxy-
α
-sanshool, 6-gingerol, ginsenoside Rb
1
were determined by high performance liquid chromatography (HPLC), to evaluate the
in vitro
release and transdermal absorption of Jiaojiang cataplasms. The mobile phase of 6-gingerol and hydroxy-
α
-sanshool was water-acetonitrile-methanol (2∶1∶1) with the detection wavelength of 280 nm. The mobile phase of ginsenoside Rb
1
was acetonitrile-0.1% phosphoric acid aqueous solution (31∶69) with the detection wavelength of 203 nm. A mouse intestinal paralysis model was established, and mice were randomly divided into five groups, namely sham operation group, model group, domperidone group (3.9 mg·kg
-1
) and high- and low-dose groups of Jiaojiang cataplasms (6.2, 3.1 g·kg
-1
, measured by crude drug dosage), to observe the effect of this preparation on gastrointestinal propulsion function.
Result
2
Average release rates of hydroxy-
α
-sanshool, 6-gingerol and ginsenoside Rb
1
at 24 h were 16.41, 4.23, 4.15 μg∙cm
-2
∙h
-1
, the average transdermal rates of them at 24 h were 2.31, 0.64, 0.29 μg∙cm
-2
∙h
-1
, their skin retention values were 19.56, 3.59, 1.61 μg, respectively. According to the Ritger-Peppas equation, the release of hydroxy-
α
-sanshool, 6-gingerol, ginsenoside Rb
1
was non-Fick diffusion. The high-dose group of Jiaojiang cataplasms could improve intestinal function of model mice after small intestinal friction injury, and promote intestinal peristalsis and small intestinal propulsion rate (
P
<
0.05).
Conclusion
2
Jiaojiang cataplasms has
in vitro
release and transdermal properties, the
in vitro
release conforms to Higuchi equation, and transdermal absorption behavior conforms to zero-order kinetic equation, which can improve the postoperative function of the small intestine and the propulsion function of small intestine. It preliminarily indicates that the preparation has certain clinical development value.
吕邵娃 , 潘世伟 , 付起凤 , 等 . 脐部给药剂型的发展概况与展望 [J]. 中医药学报 , 2015 , 43 ( 6 ): 109 - 112 .
YANG J G , XU H , WANG H . External application of herbal medicine to acupoints [J]. J Tradit Chin Med , 2008 , 28 ( 1 ): 21 - 23 .
RONG P J , ZHU B , LI Y Q , et al . Mechanism of acupuncture regulating visceral sensation and mobility [J]. Front Med , 2011 , 5 ( 2 ): 151 - 156 .
国家药典委员会 . 中华人民共和国药典:四部 [M]. 北京 : 中国医药科技出版社 , 2020 : 22 .
PASTORE M N , KALIA Y N , HORSTMANN M , et al . Transdermal patches:History,development and pharmacology [J]. Br J Pharmacol , 2015 , 172 ( 9 ): 2179 - 2209 .
宋立华 , 刘淑芝 . 中药凝胶膏剂的研究进展分析 [J]. 中国实验方剂学杂志 , 2015 , 21 ( 22 ): 133 - 136 .
AHSAN A , TIAN W X , FAROOQ M A , et al . An overview of hydrogels and their role in transdermal drug delivery [J]. Int J Polym Mater Polym Biomat , 2021 , 70 ( 8 ): 574 - 584 .
刘淑芝 . 中药巴布剂研究现状分析及展望 [J]. 中医外治杂志 , 2005 , 14 ( 5 ): 3 - 5 .
梁秉文 , 刘淑芝 , 梁文权 . 中药经皮给药制剂技术 [M]. 北京 : 化学工业出版社 , 2013 : 4 - 22 .
周建新 , 沈硕 , 杜茂波 , 等 . 基于UPLC-Q-TOF-MS技术和整合药理学方法探索吴茱萸经皮成分及其治疗腹泻的分子机制 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 7 ): 112 - 120 .
何爱萍 , 易红 , 冯伟红 , 等 . 活血止痛微乳凝胶剂的体外释放和透皮吸收评价 [J]. 中国实验方剂学杂志 , 2017 , 23 ( 5 ): 17 - 21 .
姚瑶 , 冯伟红 , 王岚 , 等 . 活血止痛纳米凝胶贴膏经皮渗透特性及药效评价 [J]. 中国中医药信息杂志 , 2017 , 24 ( 2 ): 70 - 75 .
杜茂波 , 毛著鸿 , 沈硕 , 等 . 工艺变更对祖师麻关节止痛膏体外释放及经皮渗透的影响 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 8 ): 135 - 141 .
杜茂波 , 刘淑芝 , 李曼玲 , 等 . 萸连巴布剂体外释放和透皮行为的研究 [J]. 中国中药杂志 , 2009 , 34 ( 8 ): 969 - 972 .
陈奇 . 中药药理学实验方法学 [M]. 北京 : 人民卫生出版社 , 1994 : 55 .
张林 , 蒋宁 , 周文霞 , 等 . 三种小鼠术后肠麻痹模型的比较研究 [J]. 国际药学研究杂志 , 2016 , 43 ( 2 ): 346 - 350 .
ENDO M , HORI M , OZAKI H , et al . Daikenchuto,a traditional Japanese herbal medicine,ameliorates postoperative ileus by anti-inflammatory action through nicotinic acetylcholine receptors [J]. J Gastroenterol , 2014 , 49 ( 6 ): 1026 - 1039 .
KALFF J C , BUCHHOLZ B M , ESKANDARI M K , et al . Biphasic response to gut manipulation and temporal correlation of cellular infiltrates and muscle dysfunction in rat [J]. Surgery , 1999 , 126 ( 3 ): 498 - 509 .
方蓉 , 郑杭生 , 陈思思 . 离体皮肤渗透法测定三七总皂苷传递体经皮吸收特性 [J]. 中草药 , 2015 , 46 ( 4 ): 513 - 519 .
何百寅 , 谢友良 , 刘常青 , 等 . 三七提取液中三七皂苷R 1 、人参皂苷Rg 1 和人参皂苷Rb 1 的透皮规律研究 [J]. 中国实验方剂学杂志 , 2011 , 17 ( 21 ): 130 - 134 .
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