环索奈德干粉吸入剂的研究及其对豚鼠哮喘的抑制作用

doi:10.5246/jcps.2011.05.060

环索奈德干粉吸入剂的研究及其对豚鼠哮喘的抑制作用

刘菲, 王桂玲, 张燕, 门萤, 杜举, 居瑞军, 张亮, 应雪, 吕万良^*, 张强^*

北京大学医学部天然药物及仿生药物国家重点实验室; 药学院药剂学系, 北京 100191

收稿日期:2011-04-08 修回日期:2011-07-08 出版日期:2011-09-20 发布日期:2011-09-20
通讯作者: 吕万良*, 张强*

Development of ciclesonide dry powder inhalers and the anti-asthmatic efficacy in guinea pigs

Fei Liu, Gui-Ling Wang, Yan Zhang, Ying Men, Ju Du, Rui-Jun Ju, Liang Zhang, Xue Ying, Wan-Liang Lu^*, Qiang Zhang^*

State Key Laboratory of Natural and Biomimetic Drugs; Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2011-04-08 Revised:2011-07-08 Online:2011-09-20 Published:2011-09-20
Contact: Wan-Liang Lu*, Qiang Zhang*

摘要/Abstract

摘要：

环索奈德是目前处于临床研究阶段, 用于治疗哮喘的新糖皮质激素类药物。本研究的目的是制备小剂量环索奈德干粉吸入剂 (DPIs, 80 μg), 并探讨其抗哮喘作用。采用球型乳糖作为稀释剂, 与微粉化环索奈德混匀, 制备环索奈德胶囊, 置于干粉吸入装置中供口服吸入用。建立豚鼠哮喘模型, 评价环索奈德抗哮喘作用。结果表明: 制备得到的环索奈德干粉吸入剂的肺部沉积率约为26%, 含量均匀度符合中国药典要求。在建立的哮喘豚鼠模型中, 哮喘豚鼠肺泡间隔增宽, 肺泡腔缩小, 支气管黏膜上皮部分坏死、脱落, 伴杯状细胞增生及嗜酸性粒细胞侵润。给予环索奈德治疗后, 肺部病理症状得到了有效缓解或恢复, 肺泡灌洗液(BALF) 中细胞总数及嗜酸性粒细胞明显减少, IL-5水平降低, IFN-γ水平升高, 表现出明显的治疗哮喘效果。本研究成功的制备了新型抗哮喘环索奈德肺部给药系统, 并在动物模型上证实了其对哮喘的抑制作用。

关键词: 环索奈德, 干粉吸入剂, 哮喘, IL-5, IFN-γ

Abstract:

Ciclesonide is a new corticosteroid currently in clinical development for the treatment of asthma by oral inhalation. The objectives of the present study were to develop ciclesonide dry powder inhalers (DPIs, 80 μg) and investigate the anti-asthmatic effect in animals. For preparing a ciclesonide capsule-type DPI, sphere-shaped lactose was used as a diluent carrier, mixed with micronized ciclesonide, and filled into a capsule, and then put into a dry powder inhaler for oral inhalation. The asthmatic model was established with guinea pigs, and the therapeutic efficacy of ciclesonide was performed on the asthmatic guinea pig model. Results showed that the pulmonary deposition ratio of ciclesonide DPIs was approximately 26% and their content uniformity met the requirements of China Pharmacopoeia. The established pathological model exhibited the typical features of asthma with a widened pulmonary alveolar interval, narrowed alveolar space and detached bronchial mucosal epithelium with topical necrosis, goblet cell hyperplasia, and inflammatory cell infiltration. After treating with ciclesonide, the impaired indicators in asthmatic guinea pigs were significantly recovered or alleviated, exhibiting decreased total cells, decreased eosinophils and a decreased IL-5 level while there was an increased IFN-γ level in the bronchoalveolar lavage fluid (BALF). This study develops a new pulmonary ciclesonide delivery system for treating asthma, and proves the therapeutic efficacy in asthmatic guinea pigs.

Key words: Ciclesonide, Dry powder inhalers, Asthma, IL-5, IFN-γ

中图分类号:

R943

Supporting:

Foundation items: Tianjin Pharmaceuticals Research Organization Co., Ltd, and in part by the Key Grant of Beijing Natural Science Foundation (Grant No. 7091005).
^*Corresponding author. Tel./Fax: 86-10-82802683

刘菲, 王桂玲, 张燕, 门萤, 杜举, 居瑞军, 张亮, 应雪, 吕万良^*, 张强^*. 环索奈德干粉吸入剂的研究及其对豚鼠哮喘的抑制作用[J]. , DOI: 10.5246/jcps.2011.05.060.

Fei Liu, Gui-Ling Wang, Yan Zhang, Ying Men, Ju Du, Rui-Jun Ju, Liang Zhang, Xue Ying, Wan-Liang Lu^*, Qiang Zhang^* . Development of ciclesonide dry powder inhalers and the anti-asthmatic efficacy in guinea pigs[J]. , DOI: 10.5246/jcps.2011.05.060.

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