Injectable formulation of disodium 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), an ultrafast nitric oxide donor prodrug.
Injectable formulation of disodium 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), an ultrafast nitric oxide donor prodrug.
复制标题
1-[2-(羧基)吡咯烷-1-基]diazen-1-ium-1,2-二醇二钠 (PROLI/NO) 的注射制剂，是一种超快速一氧化氮供体前药。
DOI：
10.1002/jps.20486
复制
发表时间：
2006
影响因子：
3.8
通讯作者：
Keefer,LarryK
中科院分区：
文献类型：
--
作者：
Waterhouse,DavidJ;Saavedra,JosephE;Davies,KeithM;Citro,MichaelL;Xu,Xia;Powell,DouglasA;Grimes,GeorgeJ;Potti,GopalK;Keefer,LarryK
PROLI/NO是一种结构为XN（O）NONa（X = L-脯氨酰基）的试剂，其在生理pH下释放一氧化氮（NO）的2-s半衰期使其成为用于将NO的治疗效果定位在应用部位的优异前药，但难以配制和证明为纯的。然而，尽管其具有非凡的热和水解不稳定性，但PROLI/NO可以通过将其溶解在含有5% D-甘露醇的冷0.1 M氢氧化钠中，然后快速超滤并在抽空的隔膜小瓶中冻干而配制成可注射药物。通过定量模拟输注液溶液（10 mM碳酸盐/碳酸氢盐，pH 10.5）中的NO释放来判断，当在−20°C下储存140天观察期时，在这些抽空小瓶的内容物中未观察到分解证据。仅检测到的水解产物为NO、亚硝酸根离子、脯氨酸和N-亚硝基脯氨酸，均为正常人体生理过程的产物。© 2005 Wiley-Liss公司。和美国药剂师协会
PROLI/NO is an agent of structure XN(O)═NONa (X = L-prolyl) whose 2-s half-life for nitric oxide (NO) release at physiological pH makes it an excellent prodrug for localizing NO's therapeutic effects at the site of application, but a difficult one to formulate and certify as pure. Despite its extraordinary thermal and hydrolytic instability, however, PROLI/NO could be formulated as an injectable drug by dissolving it in cold 0.1 M sodium hydroxide containing 5%D-mannitol, then quickly ultrafiltering and lyophilizing it in evacuated septum vials. No evidence for decomposition was seen in the contents of these evacuated vials when stored at −20°C over a 140-day observation period, as judged by quantifying NO release in simulated infusate solutions (10 mM carbonate/bicarbonate, pH 10.5). The only hydrolysis products detected were NO, nitrite ion, proline, andN-nitrosoproline, all products of normal human physiological processes. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association