燒傷治療藥Zinc Norfloxacin之合成及抗菌活性

Synthesis and Antibacterial Activity of Zinc Norfloxacin

李安榮(An-Rong Lee) ； 黃文鑫(Wen-Hsin Huang)

《Journal of Medical Sciences》 13卷6期 (1993/06) Pp. 397-404

摘要

本研究深入探討新燒傷治療藥zinc norfloxacin之合成、製劑製備及抗菌活性。燒燙傷是最常見的意外傷害，甚至在軍陣上影響戰力甚鉅。大範圍或深度燒傷，不僅傷口癒合緩慢，且影響皮膚外觀，若受到綠膿桿菌感染，更為燒傷病人死亡之主因。臨床上唯一外用燒傷治療藥物，為達淨磺胺銀（silver sulfadiazine; AgSD），然本藥具肝毒性、導致腎衰竭、價格高昂及安定性不佳，且易致過敏之缺點。本研究室曾製備達淨磺胺鋅（zinc sulfadiazine; Zn（SD）2）衍生物具優越之療效及及低毒性，然其乳膏劑型之長期安定性試驗發現外觀仍不穩定，乃著手進一步探討zinc norfolxacin (Zn（NFLX）2）是否具有強力抗菌活性及加速傷口痊癒或成本低廉之優點，以作為AgSD之取代藥物。初步結果發現Zn（NFLX）2之優點為具有強力抗綠膿桿菌活性，療效更優於達淨磺胺鋅及連淨磺胺銀。本藥製備容易，成本低廉，適合量產。本研究室將進行與其他藥物配伍，製成各種軟膏、人造皮膚製劑等之研究。本類藥物高效、低毒，為極具開發潛能之新藥。

關鍵字

燒傷治療藥 ； 抗菌活性 ； Zinc norfloxacin ； 綠膿桿菌

並列摘要

The synthesis, physicochemical properties, stability, in vitro antibacterial activity, and toxicity of zinc norfloxacin (Zn (NFLX)2; 1d) was described. Zn(NFLX)2 was redily obtained in two steps from norfloxacin (1a), a novel pyridone-carboxylic acid type antibaterial agent, by treatment with sodium hydroxide followed by zinc nitrate in a total yield of 23.9%. The structural characterization was established by UV, IR, NMR, and elemental analysis. Zn (NFLX)2 possesses fairly good stability and is reasonably soluble in water which endows itself an excellent candidate in the studies of pharmaceutical dosage forms. Compared to silver or zinc sulfadiazine, Zn(NFLX)2 exhibits superior in vitro antibacterial, notably antipseudomonal activity with low toxicity in animal study which may make Zn(NFLX)2 a valuable addition to the therapeutic armamentarium for the control of burn wound sepsis in the military field.

並列關鍵字

Drugs for burns ； Antibacterial activity ； Zinc norfolxacin ； Pseudomonas aeruginosa