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聚季铵盐保存的曲伏前列素滴眼液较苯扎氯铵和拉坦前列素滴眼液对体内眼表毒性更小。

Reduced in vivo ocular surface toxicity with polyquad-preserved travoprost versus benzalkonium-preserved travoprost or latanoprost ophthalmic solutions.

机构信息

INSERM, U968, France.

出版信息

Ophthalmic Res. 2012;48(2):89-101. doi: 10.1159/000335984.

DOI:10.1159/000335984
PMID:22473057
Abstract

The study used a validated acute in vivo model to compare a new formulation of travoprost 0.004% ophthalmic solution(travoprost PQ), preserved with polyquaternium-1 (PQ), with commercially available formulations of benzalkonium-chloride(BAK)-preserved travoprost 0.004% ophthalmic solution(travoprost BAK) and BAK-preserved latanoprost 0.005%ophthalmic solution (latanoprost BAK). Adult male New Zealand albino rabbits (n = 36) were randomly divided into 6 groups. Phosphate-buffered saline (PBS), 0.001% PQ, 0.015% BAK, travoprost PQ, travoprost BAK or latanoprost BAK were applied onto rabbit eyes as 1 drop, for 15 times at 5-min intervals.The ocular surface reactions were investigated at hour 4 and day 1 using slitlamp examination; in vivo confocal microscopy (IVCM) for cornea, limbus and conjunctiva/conjunctiva-associated lymphoid tissue, conjunctival impression cytology and standard immunohistology in cryosections for detecting CD45+ infiltrating cells and MUC-5AC-labeled cells. PBS, PQ and travoprost PQ did not induce obvious irritation by clinical observation, changes in microstructures of the whole ocular surface as measured by IVCM analysis,inflammatory infiltration or cell damage as measured by impression cytology, altered levels of goblet cell counts or numerous CD45+ cells in the cornea. In contrast, all BAK-containing products induced diffuse conjunctival hyperemia and chemosis, abnormal changes in the ocular surface microstructure,significant total ocular surface toxicity scores,damaged epithelial cells, inflammatory cell infiltration and decreased goblet cell density. Travoprost PQ did not elicitocular surface toxicity when administered to rabbit eyes.These results suggest a greater safety advantage for the ocular surface of patients receiving chronic glaucoma treatment with PQ-preserved drugs.

摘要

该研究使用经过验证的急性体内模型比较了一种新的 travoprost 0.004%眼用溶液(travoprost PQ)配方,该配方用多聚季铵盐-1(PQ)保存,与市售的苯扎氯铵(BAK)保存 travoprost 0.004%眼用溶液(travoprost BAK)和 BAK 保存的拉坦前列素 0.005%眼用溶液(latanoprost BAK)进行比较。成年雄性新西兰白兔(n=36)随机分为 6 组。用磷酸盐缓冲盐水(PBS)、0.001%PQ、0.015%BAK、travoprost PQ、travoprost BAK 或 latanoprost BAK 滴眼,每次 1 滴,5 分钟间隔 15 次。在第 4 小时和第 1 天,通过裂隙灯检查;角膜、角膜缘和结膜/结膜相关淋巴组织的共焦显微镜(IVCM);结膜印片细胞学;和冷冻切片的标准免疫组织化学,检测 CD45+浸润细胞和 MUC-5AC 标记细胞,来评估眼表面反应。临床观察、IVCM 分析测量的整个眼表面微观结构变化、炎症浸润或印迹细胞学测量的细胞损伤、杯状细胞计数或角膜中 CD45+细胞数量的改变均表明 PBS、PQ 和 travoprost PQ 没有引起明显的刺激。相反,所有含 BAK 的产品均引起弥漫性结膜充血和水肿、眼表面微观结构异常改变、总眼表面毒性评分显著升高、上皮细胞损伤、炎症细胞浸润和杯状细胞密度降低。travoprost PQ 滴眼后不会引起兔眼表面毒性。这些结果表明,在接受慢性青光眼治疗的患者中,使用 PQ 保存药物可能具有更大的眼表面安全性优势。

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