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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,80μg),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。
Ciclesonide is currently in clinical research stage for the treatment of asthma neo-glucocorticoid drugs. The purpose of this study was to prepare small doses of ciclesonide dry powder inhaler (DPIs, 80μg), and explore its anti-asthmatic effect. The use of globular lactose as diluent, and micronized ciclesonide mixing, preparation of ciclesonide capsules, placed in a dry powder inhalation device for oral inhalation. Establishment of guinea pig asthma model, evaluation of ciclesonide anti-asthma. The results showed that the lung deposition rate of the prepared Ciclesonide powder inhaler was about 26%, and the content uniformity was in line with the requirements of Chinese Pharmacopoeia. In the established model of asthmatic guinea pigs, the alveolar septa of asthmatic guinea pigs were broadened, the alveolar space was narrowed, the bronchial mucosal epithelium was partially necrotic and exfoliated, with goblet cell hyperplasia and eosinophil infiltration. After treatment with ciclesonide, pulmonary pathological symptoms were effectively relieved or recovered. The total number of cells and eosinophils in BALF were significantly decreased, the level of IL-5 was decreased, the level of IFN-γ was increased, Showed a clear effect of treatment of asthma. This study successfully prepared a new anti-asthma Ciclesonide pulmonary delivery system, and in animal models confirmed its inhibition of asthma.