2nd Department of Biochemistry Faculty of Pharmaceutical Sciences, Mukogawa Women's University.
Senju Pharmaceutical Co., LTD.
Chem Pharm Bull (Tokyo). 2023;71(7):552-557. doi: 10.1248/cpb.c23-00115.
Benzalkonium chloride (BAC) is a useful preservative for ophthalmic solutions but has some disadvantageous effects on corneal epithelium, especially keratinocytes. Therefore, patients requiring the chronic administration of ophthalmic solutions may suffer from damage due to BAC, and ophthalmic solutions with a new preservative instead of BAC are desired. To resolve the above situation, we focused on 1,3-didecyl-2-methyl imidazolium chloride (DiMI). As a preservative for ophthalmic solutions, we evaluated the physical and chemical properties (absorption to a sterile filter, solubility, heat stress stability, and light/UV stress stability), and also the anti-microbial activity. The results indicated that DiMI was soluble enough to prepare ophthalmic solutions, and was stable under severe heat and light/UV conditions. In addition, the anti-microbial effect of DiMI as a preservative was considered to be stronger than BAC. Moreover, our in vitro toxicity tests suggested that DiMI is safer to humans than BAC. Considering the test results, DiMI may be an excellent candidate for a new preservative to replace BAC. If we can overcome manufacturing process issues (soluble time and flushing volume) and the insufficiency of toxicological information, DiMI may be widely adopted as a safe preservative, and immediately contribute to the increased well-being of all patients.
苯扎氯铵（BAC）是一种有用的眼用溶液防腐剂，但对角膜上皮，特别是角朊细胞有一些不利影响。因此，需要长期使用眼用溶液的患者可能会因 BAC 而受损，需要一种用新防腐剂替代 BAC 的眼用溶液。为了解决上述情况，我们专注于 1,3-二癸基-2-甲基咪唑啉氯化物（DiMI）。作为眼用溶液的防腐剂，我们评估了其物理化学性质（对无菌过滤器的吸收、溶解度、热应激稳定性和光/UV 应激稳定性）和抗菌活性。结果表明，DiMI 具有足够的溶解度以制备眼用溶液，并且在剧烈的热和光/UV 条件下稳定。此外，DiMI 作为防腐剂的抗菌效果被认为比 BAC 更强。此外，我们的体外毒性试验表明，DiMI 比 BAC 对人体更安全。考虑到这些测试结果，DiMI 可能是替代 BAC 的一种优秀的新型防腐剂候选物。如果我们能够克服制造工艺问题（溶解度时间和冲洗量）和毒理学信息不足，DiMI 可能会被广泛用作一种安全的防腐剂，并立即为所有患者的福祉增加做出贡献。
