雷公藤甲素阿魏酸醇质体凝胶的制备与经皮渗透性研究
|
摘要
采用改良后的Franz扩散池法,以小鼠腹部皮肤为模型进行体外透皮扩散,收集不同时间点的接收液,用HPLC测定其中阿魏酸的浓度、用LC-MS/MS测定雷公藤甲素的浓度,比较醇质体凝胶、普通凝胶、乳膏3种剂型的透皮速度、透皮量与皮肤储量的差别,以探索雷公藤甲素阿魏酸醇质体凝胶中阿魏酸、雷公藤甲素的体外透皮特性并与普通凝胶组和乳膏组比较。结果,雷公藤甲素阿魏酸醇质体凝胶、普通凝胶和乳膏中阿魏酸稳态透皮速率分别为5.268 5,8.990 9,12.042 0μg·cm~(-2)·h~(-1),皮肤滞留量分别(30.234 8±1.525 4),(20.402 6±0.402 6),(7.635 3±1.094 2)μg·cm~(-2);雷公藤甲素阿魏酸醇质体凝胶中雷公藤甲素的稳态透皮速率为67.238 0 ng·cm~(-2)·h~(-1)约为乳膏的1.24倍,普通凝胶的3.28倍,皮肤滞留量为(371.351 4±35.317 1)ng·cm~(-2)约为乳膏的3.35倍,普通凝胶的5.25倍。故雷公藤甲素阿魏酸醇质体凝胶透皮效果良好,有助于临床安全给药。
The aim of this study was to prepare triptolide and ferulic acid ethosomes gel,investigate its transdermal permeation,and compare the results with ordinary gel and cream. Improved Franz diffusion cell method was used in the transdermal delivery experiment with rat abdominal skin as in vitro model. The receptor fluid at different time points was collected; ferulic acid concentration was determined by high performance liquid chromatography( HPLC) and triptolide concentration was determined by liquid chromatography-electrospray ionization mass spectrometry( LC-MS/MS). Then the penetration rate,transdermal volume and skin reserve of three dosage forms( hydroplasy gel,ordinary gel,and cream) to investigate the transdermal properties of ferulic acid and triptolide in vitro of triptolide and ferulic acid ethosomes gel. The results showed that the steady penetration rate of ferulic acid was 5. 268 5,8. 990 9,12. 042 0μg·cm~(-2)·h~(-1) respectively in triptolide and ferulic acid ethosomes gel,ordinary gel and cream; the skin retention was( 30. 234 8 ±1. 525 4),( 20. 402 6 ± 0. 402 6),( 7. 635 3 ± 1. 094 2) μg·cm~(-2). The steady-state permeation rate of triptolide was 67. 238 0,67. 238 0 ng·cm~(-2)·h~(-1) in triptolide and ferulic acid ethosomes gel,about 1. 24 times of cream and 3. 28 times of ordinary gel; the skin retention was( 371. 351 4 ± 35. 317 1) ng·cm~(-2),about 3. 35 times of cream and 5. 25 times of ordinary gel. Therefore,the ethosomes gel showed good transdermal absorption property and it may be good for clinical safety administration.
The aim of this study was to prepare triptolide and ferulic acid ethosomes gel,investigate its transdermal permeation,and compare the results with ordinary gel and cream. Improved Franz diffusion cell method was used in the transdermal delivery experiment with rat abdominal skin as in vitro model. The receptor fluid at different time points was collected; ferulic acid concentration was determined by high performance liquid chromatography( HPLC) and triptolide concentration was determined by liquid chromatography-electrospray ionization mass spectrometry( LC-MS/MS). Then the penetration rate,transdermal volume and skin reserve of three dosage forms( hydroplasy gel,ordinary gel,and cream) to investigate the transdermal properties of ferulic acid and triptolide in vitro of triptolide and ferulic acid ethosomes gel. The results showed that the steady penetration rate of ferulic acid was 5. 268 5,8. 990 9,12. 042 0μg·cm~(-2)·h~(-1) respectively in triptolide and ferulic acid ethosomes gel,ordinary gel and cream; the skin retention was( 30. 234 8 ±1. 525 4),( 20. 402 6 ± 0. 402 6),( 7. 635 3 ± 1. 094 2) μg·cm~(-2). The steady-state permeation rate of triptolide was 67. 238 0,67. 238 0 ng·cm~(-2)·h~(-1) in triptolide and ferulic acid ethosomes gel,about 1. 24 times of cream and 3. 28 times of ordinary gel; the skin retention was( 371. 351 4 ± 35. 317 1) ng·cm~(-2),about 3. 35 times of cream and 5. 25 times of ordinary gel. Therefore,the ethosomes gel showed good transdermal absorption property and it may be good for clinical safety administration.
引文
[1]胡晓敏,宗英,余珊珊,等.类风湿关节炎治疗药物的研发进展及趋势[J].中国新药杂志,2017,26(1):36.
[2]王均琴,李国春,周学平,等.雷公藤提取物治疗类风湿关节炎的Meta分析[J].现代中西医结合杂志,2014,23(10):1032.
[3]Fan D,He X,Bian Y,et al.Triptolide Modulates TREM-1 signal pathway to inhibit the inflammatory response in Rheumatoid Arthritis[J].Int J Mol Sci,2016,17(4):498.
[4]余雅婷,朱卫丰,金晨,等.雷公藤甲素的剂型改进及给药方式研究进展[J].中国新药杂志,2016,25(12):1359.
[5]陶玲,肖芳,朱卫丰,等.雷公藤减毒研究进展[J].中国实验方剂学杂志,2017,23(5):229.
[6]Mancuso C,Santangelo R.Ferulic acid:pharmacological and toxicological aspects[J].Food Chem Toxicol,2014,65(2):185.
[7]Tsai C Y,Woung L C,Yen J C,et al.Thermosensitive chitosanbased hydrogels for sustained release of ferulic acid on corneal wound healing[J].Carbohydr Polym,2016,135:308.
[8]Liang Q,Ju Y,Chen Y,et al.Lymphatic endothelial cells efferent to inflamed joints produce i NOS and inhibit lymphatic vessel contraction and drainage in TNF-induced arthritis in mice[J].Arthritis Res Ther,2016,18(1):62.
[9]毕建云,刘善新,靳光乾,等.阿魏酸透皮吸收研究综述[J].中药材,2013,36(6):1028.
[10]张艳,李周,王利胜.双藤微乳凝胶的制备和体外释放度的考察[J].今日药学,2017,27(3):145.
[2]王均琴,李国春,周学平,等.雷公藤提取物治疗类风湿关节炎的Meta分析[J].现代中西医结合杂志,2014,23(10):1032.
[3]Fan D,He X,Bian Y,et al.Triptolide Modulates TREM-1 signal pathway to inhibit the inflammatory response in Rheumatoid Arthritis[J].Int J Mol Sci,2016,17(4):498.
[4]余雅婷,朱卫丰,金晨,等.雷公藤甲素的剂型改进及给药方式研究进展[J].中国新药杂志,2016,25(12):1359.
[5]陶玲,肖芳,朱卫丰,等.雷公藤减毒研究进展[J].中国实验方剂学杂志,2017,23(5):229.
[6]Mancuso C,Santangelo R.Ferulic acid:pharmacological and toxicological aspects[J].Food Chem Toxicol,2014,65(2):185.
[7]Tsai C Y,Woung L C,Yen J C,et al.Thermosensitive chitosanbased hydrogels for sustained release of ferulic acid on corneal wound healing[J].Carbohydr Polym,2016,135:308.
[8]Liang Q,Ju Y,Chen Y,et al.Lymphatic endothelial cells efferent to inflamed joints produce i NOS and inhibit lymphatic vessel contraction and drainage in TNF-induced arthritis in mice[J].Arthritis Res Ther,2016,18(1):62.
[9]毕建云,刘善新,靳光乾,等.阿魏酸透皮吸收研究综述[J].中药材,2013,36(6):1028.
[10]张艳,李周,王利胜.双藤微乳凝胶的制备和体外释放度的考察[J].今日药学,2017,27(3):145.