左氧氟沙星与曲安奈德双载药温敏泪道凝胶的制备及评价

Preparation and Evaluation of Thermoresponsive Double-drug Loaded Lacrimal Duct Gel Containing Levofloxacin and Triamcinolone Acetonide

目的:制备左氧氟沙星和曲安奈德温敏型双载药泪道凝胶,以期用于泪道阻塞性疾病防治。方法:以泊洛沙姆407为基质,泊洛沙姆188为凝胶增强剂,以人工泪液稀释前后的胶凝温度为考察指标,确定合适的凝胶基质处方。再以盐酸左氧氟沙星和醋酸曲安奈德为主药,制备温敏型双载药泪道凝胶,测定凝胶的含药量,并考察凝胶体外溶蚀行为。建立泪道阻塞动物模型,进一步考察凝胶对泪道炎症的作用。结果:最佳凝胶基质组成为:泊洛沙姆188浓度为10%,泊洛沙姆407浓度为18%。所制得的温敏型双载药泪道凝胶中,盐酸左氧氟沙星的标示含量为(97.4±0.72)%,醋酸曲安奈德的标示含量为(92.98±0.85)%,体外溶蚀行为持续缓慢,在阻塞局部具有显著的抗炎作用。结论:成功制得温敏型双载药泪道凝胶。

Objective: To prepare levofloxacin and triamcinolone acetonide thermoresponsive lacrimal duct gel to apply in the treatment and prevention of lacrimal duct obstructive disease( LDOD). Methods: Using poloxamer 407 as the base material and poloxamer188 as the gelling enhancer,and the gelation temperature in the artificial tear before and after dilution as the evaluation index,the best gel matrix formulation was identified. Levofloxacin hydrochloride and triamcinolone acetonide were used as the main drugs to prepare thermosensitive double-drug loaded lacrimal duct gel. The drug contents in the gel were determined,and the dissolution behavior of the gel in vitro was investigated. An animal model of lacrimal duct obstruction was established to further investigate the effect of the gel on lacrimal duct inflammation. Results: The best gel matrix was as follows: the concentration of poloxamer 188 was 10% and that of poloxamer 407 was 18%. The content of levofloxacin hydrochloride in the gel was( 97. 4 ± 0. 72)%,and that of triamcinolone acetonide was( 92. 98 ± 0. 85)%. The dissolution behavior in vitro was sustained and slow,and the anti-inflammatory effect in obstructive areas was remarkable. Conclusion: Levofloxacin and triamcinolone acetonide thermoresponsive double-loaded lacrimal duct gel is prepared successfully.