作者：余方坤1, 张倩1, 李岭慧1, 徐新兰2, 李锐1, 肖洪涛3, 侯曙光1,2
作者单位：1. 成都中医药大学药学院, 四川 成都 611137;
2. 四川普锐特药业有限公司, 四川 成都 610041;
3. 四川省肿瘤医院&研究所, 四川 成都 610072
关键词：鼻喷雾剂;质量控制;hplc;粒度分布;喷雾模式;喷雾形态
摘要：
为建立高效液相色谱 (hplc) 法同时测定克敏芪丹鼻喷剂中升麻素苷、毛蕊异黄酮葡萄糖苷、阿魏酸、山梨酸钾、5-o-甲基维斯阿米醇苷的含量；并采用激光粒度测定仪考察制剂的粒径分布、喷雾模式和喷雾形态。采用boston-c18柱 (250 mm×4.6 mm，5 μm) 色谱柱；0.05%磷酸水溶液-乙腈的流动相，梯度洗脱；流量为1.0 ml/min；柱温为25 ℃；进样量为10 μl，检测波长为300 nm。采用spraytecness喷雾粒度测定仪、牛津激光测定仪考察制剂的喷雾特性。 结果表明：5种成分在相应浓度范围内线性关系良好；精密度、稳定性、重复性良好，rsd<1.36%；平均加样回收率在100.68%~105.34%，rsd<1.13%；喷雾形态角度在39°左右；喷雾模式椭圆率在1.16%~1.27%；雾滴粒径主要集中在13~85 μm范围内，v%<10 μm的雾滴小于5%。该hplc方法操作简便，专属性强，准确灵敏，重复性好；克敏芪丹鼻喷剂喷雾特性良好。该方法可为克敏芪丹鼻喷剂及其类方制剂的新药开发提供参考。
content determination of five index components in keminqidan nasal spray and investigation of spray characteristics of the preparation
yu fangkun1, zhang qian1, li linghui1, xu xinlan2, li rui1, xiao hongtao3, hou shuguang1,2
1. school of pharmacy, chengdu university of traditional chinese medicine, chengdu 611137, china;
2. sichuan purity pharmaceutical co., ltd., chengdu 610041, china;
3. sichuan cancer hospital & institute, chengdu 610072, china
abstract: to develop an hplc method for the simultaneous determination of cimicifugin, calycosin-7-o-β-d-glucoside, ferulic acid, potassium sorbate and 4'-o-β-d-glucosyl-5-o-methyl-visamminol in keminqidan nasal spray. the droplet size distribution, spray pattern and plume geometry of the preparation were investigated by laser particle size analyzer. a boston-c18 column (250 mm×4.6 mm, 5 μm) was used, and gradient elution was performed with mobile phases composed of 0.05% phosphoric acid aqueous solution-acetonitrile, with the flow rate at 1.0 ml/min, column temperature at 25℃, and injection volume of 10 μl. the detection wavelength was set at 300 nm. the spraytec laser particle size analyzer and oxford laser particle size analyzer were used to investigate the spray characteristics of the preparation. good linear relationships were obtained for each compound within their analytical concentration ranges. the rsds of precision, stability and repeatability tests were less than 1.36%, and the average recoveries of accuracy were 100.68%-105.34% with rsds<1.13%. the angle of plume geometry is about 39°; the ovality of spray pattern is in the range of 1.16%-1.27%; the droplet size is mainly concentrated in the range of 13-85 μm, the droplets with v%<10 μm are less than 5%. the hplc method were developed and fully validated with accepted specificity, accuracy,sensitivity and precision. it indicated that keminqidan nasal spray had good spray characteristics. the methods can provide reference for the new drug development of keminqidan nasal spray and its similar formulations.
keywords: nasal spray;quality control;hplc;droplet size distribution;spray pattern;plume geometry
2023, 49(5):60-68 收稿日期: 2021-12-24;收到修改稿日期: 2022-03-16
基金项目: 国家自然科学基金面上项目(82073994)；四川省杰出青年科技人才基金(2020jdjq0049)；成都大学农业部杂粮加工重点实验室开放课题(2019cc02)；成都中医药大学杏林学者学科人才科研提升计划(xsgg2019005)；教育部春晖计划(20191083-127)
作者简介: 余方坤(1997-),女,四川内江市人,硕士研究生,专业方向为中药新制剂、新剂型与产品开发研究
参考文献
[1] 郑劼, 包凯帆, 李伟, 等. 基于益气固表功效探讨玉屏风散抗过敏复发的作用及机制[j]. 南京中医药大学学报, 2019, 35(5): 606-612
[2] 郭惟, 何颖贤, 张徐文, 等. 玉屏风散加减辅助治疗过敏性鼻炎的系统评价[j]. 中国药房, 2017, 28(21): 2947-2950
[3] 易欣, 田理. 克敏芪丹鼻喷剂治疗气虚血瘀型变应性鼻炎的临床疗效观察[j]. 中医眼耳鼻喉杂志, 2017, 7(4): 232-234
[4] 李亮亮, 黄金智. 毛蕊异黄酮葡萄糖苷药理作用的研究进展[j]. 海南医学院报, 2020, 26(2): 156-160
[5] 刘双利, 姜程曦, 赵岩, 等. 防风化学成分及其药理作用研究进展[j]. 中草药, 2017, 48(10): 2146-2152
[6] 梁瑞峰, 李兵杰, 葛文静, 等. 防风不同提取部位的燥性差异及其对胶原诱导性关节炎大鼠滑膜水通道蛋白的影响[j]. 中草药, 2021, 52(11): 3312-3320
[7] 李海刚, 胡晒平, 周意, 等. 川芎主要药理活性成分药理研究进展[j]. 中国临床药理学与治疗学, 2018, 23(11): 1302-1308
[8] 国家药典委员会. 中华人民共和国药典: 一部[m]. 北京: 中国医药科技出版社, 2020: 781-783.
[9] 周劲松, 张洪坤, 黄玉瑶, 等. 多波长hplc法测定玉屏风散中10种化学成分的含量[j]. 药物分析杂志, 2016(6): 1072-1081
[10] 丁慧, 顾伟伟, 季律, 等. 玉屏风散水煎液hplc指纹图谱的建立及9种成分测定[j]. 中成药, 2017(12): 2550-2554
[11] 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: 8.
[12] us food and drug administration. guidance for industry. bio-availability and bioequivalence studies for nasal aerosols and nasal sprays for local action draft guidance [eb/ol], 2003 [2021-07-12]. https://www.fda.gov/media/70867/download.
[13] 史蒂芬·纽曼, 保拉·安德森, 彼特·拜伦. 呼吸道药物递送的基本理论与实践[m]. 金方, 侯曙光, 译. 北京: 化学工业出版社, 2011: 82-83.
[14] 谢文彬, 吴磊, 李雨珂, 等. hplc-dad法同时测定利咽喷雾剂中7种成分[j]. 中国新药杂志, 2019, 28(13): 1635-1641
[15] 李荣荣, 刘海侠, 彭培好, 等. 四川牡丹皮uplc指纹图谱研究及4种成分的同时测定[j]. 中国测试, 2021, 47(8): 77-82
[16] 袁海英, 蔡帮军, 侯新莲, 等. 一测多评法测定参附注射液中6种人参皂苷的含量[j]. 中国测试, 2020, 46(2): 50-55
[17] 邓春丽, 王晓飞, 沙先谊, 等. 三七总皂苷鼻腔喷雾剂的喷雾特性考察[j]. 中国医药工业杂志, 2015, 46(9): 970-984
[18] 石远, 仝新勇, 陈亮, 等. 黏度和触发参数对混悬型鼻喷雾剂雾滴粒度分布的影响[j]. 中国新药与临床杂志, 2010, 29(12): 899-903
