DNJ双层渗透泵片的制备及比格犬体内药动学研究

doi:10.3969/j.issn.1673-5854.2018.06.008

生物质化学工程 ›› 2018, Vol. 52 ›› Issue (6): 51-56.doi: 10.3969/j.issn.1673-5854.2018.06.008

DNJ双层渗透泵片的制备及比格犬体内药动学研究

孙照英¹, 聂彦彦², 赵华南³, 刘志明¹

1. 东北林业大学材料科学与工程学院, 黑龙江哈尔滨 150040;
2. 青岛海慈医疗集团, 山东青岛 266100;
3. 哈药集团技术中心, 黑龙江哈尔滨 150020

收稿日期:2017-08-25 出版日期:2018-11-30 发布日期:2018-12-12
通讯作者: 刘志明,教授,博士,博士生导师,主要从事生物质材料化学、纤维素气凝胶和纳米纤维素、木质素及其复合功能材料研究;E-mail:zhimingliuwhy@126.com。 E-mail:zhimingliuwhy@126.com
作者简介:孙照英(1980-),女,黑龙江哈尔滨人,博士生,主要从事纤维素衍生物药物缓控释研究;E-mail:554610961@qq.com
基金资助:
黑龙江省自然科学基金项目（C2015055）；林业公益性行业科研专项（201504602）；哈尔滨市科技创新人才项目（2014RFXXJ038）

Preparation of DNJ Bi-layer Osmotic Pump Tablets and Its Pharmacokinetics Study in Beagle Dogs

SUN Zhaoying¹, NIE Yanyan², ZHAO Huanan³, LIU Zhiming¹

1. College of Material Science and Engineering, Northeast Forestry University, Harbin 150040, China;
2. Qingdao Hiser Medical Center, Qingdao 266100, China;
3. Harbin Pharmaceutical Group R & D Center, Harbin 150020, China

Received:2017-08-25 Online:2018-11-30 Published:2018-12-12

摘要/Abstract

摘要： 制备了1-脱氧野尻霉素（DNJ）双层渗透泵片，以释放度为评价指标优化了处方，考察了DNJ双层渗透泵片的体外释药性，并对比研究了DNJ双层渗透泵片和速释片在比格犬体内的药动学。DNJ双层渗透泵片的最优处方为含药层羟丙基甲基纤维素（HPMC） E50用量为10 mg、助推层聚氧乙烯（PEO，M_r 6×10⁶）用量为80 mg 、包衣层醋酸纤维素（CA）用量为15 mg及聚乙二醇（PEG）4000用量为5 mg，在此条件下DNJ溶出速度最为适宜，并且不受pH值的变化影响，药物12 h溶出完全，且恒速缓慢释放。对比DNJ双层渗透泵片和速释片在比格犬体内的双制剂双周期交叉试验，结果表明：双层渗透泵片释放的达峰时间（t_max）为（9.3±3.8）h比速释片（4.4±2.2）h显著延迟，达到了缓控释的目的，渗透泵片的相对生物利用度为（96.1±9.8）%，90%置信区间为84.8%~103.7%，渗透泵片与速释片吸收程度生物等效。

关键词: 1-脱氧野尻霉素, 双层渗透泵片, 溶出曲线, 药动学

Abstract: The 1-deoxynojirimycin(DNJ) bi-layer osmotic pump tablets were prepared, and the prescription was optimized by dissolution. The in vitro release of DNJ bi-layer osmotic pump tablets was investigated. And the pharmacokinetics of bi-layer osmotic pump tablets and immediate release tablets were studied in Beagle dogs. The optimal prescription for DNJ bi-layer osmotic pump tablets was the dosage of containing drug layer hydroxypropylmethyl cellulose(HPMC) E50 10 mg, the boost layer polyoxyethylene(PEO, M_r6×10⁶) 80 mg, the coating layer cellulose acetate(CA) 15 mg and polyethylene glycol(PEG) 4000 5 mg. Under these conditions, the dissolution rate of DNJ was the most suitable, and it was not affected by the change of pH value. The drug was completely dissolved in 12 h and slowly released at a constant rate. Comparing the bi-dose two-cycle crossover test of DNJ bi-layer osmotic pump tablets and immediate release tablets in Beagle dogs, the results showed that the time to peak(t_max) (9.3±3.8) h of the release of bi-layer osmotic pump tablets was longer than that of the immediate release tablets (4.4±2.2) h, achieving the purpose of controlled release. The relative bioavailability of osmotic pump tablets was (96.1±9.8)%, and the 90% confidence interval was 84.8%-103.7%. And the absorption degrees of osmotic pump tablets and immediate release tablets were organisms equivalent.

Key words: 1-deoxynojirimycin, bi-layer osmotic pump tablets, cumulative release, pharmacokinetics

中图分类号:

TQ35

孙照英, 聂彦彦, 赵华南, 刘志明. DNJ双层渗透泵片的制备及比格犬体内药动学研究[J]. 生物质化学工程, 2018, 52(6): 51-56.

SUN Zhaoying, NIE Yanyan, ZHAO Huanan, LIU Zhiming. Preparation of DNJ Bi-layer Osmotic Pump Tablets and Its Pharmacokinetics Study in Beagle Dogs[J]. bce, 2018, 52(6): 51-56.

参考文献

[1] KIMURA T,NAKAGAWA K,KUBUTA H,et al. Food-grade mulberry powder enriched with 1-deoxynojirimycin suppresses the elevation of postprandial blood glucose in human[J]. Journal of Agricultural and Food Chemistry,2007,55(14):5869-5874.
[2] WENNEKES T,RICHARD J B,BERG V D,et al. Development of adamantan-1-yl-methoxy-functionalized 1-deoxynojirimycin derivatives as selective inhibitors of glucosylceramide metabolism in man[J]. Journal of Organic Chemistry,2007,72(4):1088-1097.
[3] VICHASILP C,NAKAGAWA K,SOOKWONG P,et al. Development of high 1-DNJ content mulberry tea and use of response surface methodology to optimize tea-making conditions for highest DNJ extraction[J]. LWT-Food Science and Technology,2012,45(2):226-232.
[4] 章靖芳,苏峰,刘为中,等. 渗透泵药物传递系统制备技术研究进展[J]. 安徽医药,2017,21(4):591-594.
[5] 陈伶俐,罗燕娜,朱翠霞,等. 口服渗透泵缓控释给药系统的研究概况[J]. 中国民族民间医药,2017,26(14):61-65.
[6] 王健,王浩,侯惠民. 药物制剂国家工程研究中心近十年研究进展[J]. 中国医药工业杂志,2017,48(3):293-306.
[7] 章靖芳,苏峰,刘为中,等. 渗透泵药物传递系统制备技术研究进展[J]. 安徽医药,2017,21(4):591-594.
[8] HERRLICH S,SPIETH S,MESSNER S,et al. Osmotic micropumps for drug delivery[J]. Advanced Drug Delivery Reviews,2012,64(14):1617-1627.
[9] KUMARAVELRAJAN R,NARAYAN N,SUBA V,et al. Simultaneous delivery of Nifedipine and Metoprolol tartarate using sandwiched osmotic pump tablet system[J]. International Journal of Pharmaceutics,2010,399(1/2):60-70.
[10] 邱阳,吴超,赵宗哲,等. SBA-15增溶非洛地平的双层渗透泵片的制备[J]. 中国新药杂志,2016(7):823-829.
[11] 朱兰琼,刘辉,廖诗琴,等. 盐酸地芬尼多双层渗透泵片的制备及体外释放研究[J]. 中国药房,2017,28(13):1823-1826.
[12] 国家药典委员会. 中华人民共和国药典2015年版[M]. 北京:中国医药科技出版社,2015:866.
[13] ZHANG Z H,DONG H Y,PENG B,et al. Design of an expert system for the development and formulation of push-pull osmotic pump tablets containing poorly water-soluble drugs[J]. International Journal of Pharmaceutics,2011,410(1/2):41-47.
[14] YIN L F,HUANG S H,ZHU C L,et al. In vitro and in vivo studies on a novel solid dispersion of repaglinide using polyvinylpyrrolidone as the carrier[J]. Drug Development and Industrial Pharmacy,2012,38(11):1371-1380.
[15] 徐兵勇,潘迎锋,平丽. 左乙拉西坦缓释片的制备及其Beagle犬体内药动学研究[J]. 中国现代应用药学,2017,34(9):1266-1271.
[16] 吕小波,张明泽,黄春球,等. 血塞通分散片和普通片在比格犬体内的药动学研究[J]. 中国药学杂志,2018(1):52-57.
[17] ZHANG Z H,WANG C G,SUN G M,et al. Pharmacokinetics of two modified release system of dipyridamole in beagle dogs[J]. Jourmal of Chinese Pharmaceutical Sciences,2008,17(4):297-302.
[18] 张琳,林晓冬,刘娜,等. 富马酸喹硫平缓释片体外释放及体内外相关性研究[J]. 食品与药品,2017,19(4):235-240.

DNJ双层渗透泵片的制备及比格犬体内药动学研究

Preparation of DNJ Bi-layer Osmotic Pump Tablets and Its Pharmacokinetics Study in Beagle Dogs

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 2

编辑推荐

Metrics

本文评价

关于本刊

投稿指南

在线期刊

相关单位

联系我们

[1]	孙照英,赵华南,刘志明. 1-脱氧野尻霉素控释微丸的制备工艺优化及其药动学研究[J]. 生物质化学工程, 2020, 54(3): 45-53.
[2]	孙照英, 袁淑杰, 赵华南, 丁辉, 刘志明. 1-脱氧野尻霉素控释微丸的制备及其性能研究[J]. 生物质化学工程, 2018, 52(5): 25-30.