立他司特滴眼液处方工艺优化及对干眼症疗效评价OA北大核心CSTPCD
Optimization of prescription process of lifitegrast eye drops and evaluation of its efficacy for dry eye disease
为了研制更有效的用于治疗干眼症的药物,进行了立他司特滴眼液的制备研究,并进行了体内外的安全性和有效性考察.首先开发了滴眼液中立他司特的含量测定方法.通过文献调研及单因素实验确定了制剂的处方组成和制备工艺.最后通过Draize眼刺激性试验和HE染色进行滴眼液安全性评价,以泪液分泌试验及ELISA试验评价其对于干眼兔的治疗有效性.结果表明,立他司特滴眼液的最终处方组成为立他司特 5%、氯化钠 0.4%、无水磷酸氢二钠 0.3%～0.4%、五水硫代硫酸钠 0.3%,氢氧化钠 0.3%,外观为透明略带棕黄色的溶液,pH满足 7.75±0.05,渗透压 200～330 mOsmol/kg范围内,且 60℃下3个月内稳定性良好.刺激性研究与生理盐水对比无显著差异,立他司特滴眼液治疗后兔泪液分泌增加且泪液中炎症因子IL-6和IL-1β、TNF-α表达均显著性降低,且相比于市售乳剂环孢素滴眼液起效更快.结果表明,立他司特滴眼液制备方法简单,稳定性好,是干眼症快速治疗更优的选择.
In order to develop a more effective drug for dry eye disease,the preparation of lifitegrast eye drops was carried out,and the safety and efficacy of lifitegrast eye drops in vitro and in vivo were investigated.First the method for the determination of lifitegrast content was established,and then the composition and preparation process of the preparation were determined by literature review and single factor experiment.Finally,the safety of lifitegrast eye drops was evaluated by Draize eye irritation test and HE staining,and the therapeutic efficacy was evaluated by Schirmer test and ELISA test.The results showed that the final prescription of lifitegrast eye drops consisted of 5%lifitegrast,0.4%sodium chloride,0.3%-0.4%anhydrous disodium hydrogen phosphate,0.3%sodium thiosulfate pentahydrate and 0.3%sodium hydroxide.The appearance of lifitegrast eye drops was transparent and slightly brownish yellow solution,the pH was7.75±0.05,the osmotic pressure was in the range of 200-330 mOsmol/kg and it had good stability at 60℃for 3 months.There was no significant difference in irritation study compared with normal saline.Schirmer test showed that tear secretion was increased and the expression of inflammatory factors IL-6,IL-1β and TNF-α in tears were significantly decreased after treatment with lifitegrast eye drops and compared to the commercially available emulsion cyclosporine eye drops,it takes effect faster.The above results indicate that lifitegrast eye drops are simple to prepare and stable,which is a better choice for the rapid treatment of dry eye disease.
颜喜;潘宇南;王锴莉;徐千姿;沈雁;陆洋
北京中医药大学中药学院制药系,北京 102488广州市药品检验所,广州 510160中国药科大学药学院药剂系,南京 211198
药学
立他司特制备工艺方法学体内外评价干眼症
lifitegrastpreparation processmethodologyin vivo-in vitro evaluationdry eye disease
《中国药科大学学报》 2024 (002)
基于中医阴阳理论构建“蟾酥—牛黄”药对有效成分粒径可变纳米递药系统并联合光动力调控肿瘤免疫微环境的探索和实践
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国家自然科学基金项目(No.82173989) This study was supported by the National Natural Science Foundation of China(No.82173989)
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