左旋盐酸苯环壬酯鼻腔喷雾剂的评价概念.doc

左旋盐酸苯环壬酯鼻腔喷雾剂的评价 高永良 王晓青（军事医学科学院毒物药物研究所 北京 100850） [摘要] 目的方法结果Tmax为（15.78±8.65）±3.66）ng.mL-1，约是片剂的4倍，对片剂的相对生物利用度为（231±79）%。结论 [关键词]STUDY ON A NASAL SPRAY DRUG DELIVERY SYSTEM CONTAINING L-PHENCYNONATE HYDROCHLORIDE Gao Yong-liang, Wang Xiao-qing, Li Jing-lai (Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850) [ABSTRACT] OBJECTIVE: To study the security ,including mucous membrane irritation and ciliotoxicity, and pharmacokinetics of a nasal spray drug delivery system containing L-phencynonate hydrochloride and compared with the tablet on bioavailability. METHODS: Mucous membrane irritation test of rats was carried out by studing the structural and specific cellular changes of nasal mucosa after administering the spray. “toad palate mucoas method” was used to assay the ciliotoxicity of the spray. Finally, in vivo study was carried out with beagle dogs to investigate pharmacokinetics and bioavailability of the nasal spray. RESULTS: The influence of the spray on cilia structural and specific cellular changes of nasal mucosa showed together that the ciliotoxicity of the formulation was low and reversible. The results of pharmacokinetic study indicated that nasal spray fit with two compartment model in vivo with Tmax (12.5±2.74)min and Cmax (10.00±3.66)ng·mL-1, respectively 5 times and 4 folds or so higher than conventional tablets. The relative bioavailability of nasal spray was (231±79)%, compared with conventional tablets. CONCLUSIONS: The nasal spray of L-phencynonate hydrochloride developed in this study was confirmed with little ciliotoxicity, quick absorption and higher relative bioavailability. [KEY WORDS] L-phencynonate hydrochloride; nasal spray; mucous membrane irritation; ciliotoxicity; LC/MS/MS; pharmacokinetics; bioavailability 盐酸苯环壬酯是军事医学科学院毒物药物研究所发明的中枢抗胆碱能国家一类新药，拥有中国专利两项和英美专利各一项。盐酸苯环壬酯片上市十多年来，用于晕动病的防治，具有疗效强，中枢不良反应小的优点。进一步的动物研究及临床报告表明，该药对椎动脉供血不足引起的眩晕、位置性眩晕、帕金森氏综合症和癫痫等，同样具有较好的疗效。目前已证实分离得到的两种光学异构体中，左旋盐酸苯环壬酯是活性异构