臺灣博碩士論文加值系統

新一代 quinolone 抗菌劑的出現在化學療法上為一重要的進展，由於它們特殊的抗菌範圍及其優異的組織滲透力，使得這一類藥物於臨床的使用上日形重要，在本實驗室一系列 quinolone 之體外經皮吸收試驗後發現'：enoxacin 之透皮效果最佳，因此，本實驗中將針對 enoxacin 作更進一步之經皮吸收研究。
Enoxacin 為一種兩性化合物 (pka1=6.4, pka2=8.4)，所以其溶解度明顯地受到溶液酸值的影響，左偏酸或偏鹼的環境下有較高的溶解度，而分配係數則於中性環境中較高，在不同 pH 值的溶液中，enoxacin 的穿透速率有明顯改變，以 pH=3 時最好，pH=8 時最差；經由去角質皮膚的適透實驗後得知：對於去角質皮膚的穿透速率約為完整皮膚的四倍，角質層為 enoxacin 穿透皮膚的一大障礙。
界面活性劑中以陽離子性界面活性劑 (benzalkonium chloride) 的促進效果最佳，無論在酸性或鹼性的緩衝液抑或純水溶液中均有很好的促進作用，在穿透速率上，促進效果最高可達300倍之多，且benzalkonium chloride 的添加有助於延滯時間縮短，enoxaccin 可以更快速地穿透皮膚；陰離子性界面活性劑 (sodium lauryl sulfate) 則呈現不同的促進作用，於酸性環境中對 enoxacin 之穿透呈抑制作用，在鹼性環境中則具有促進效果，且與其濃度有關，最佳的促進作用出現於 pH=10 濃度為 3% 時，穿透速率增加 166.49 倍；非離子性界面活性劑 (Tween 80) 對 enoxacin 之經皮吸收則無顯著的影響。
β-cyclodextrin 濃度增加對 enoxacin 溶解度影響不大，經由三種方式製備 enoxacin 與β-cyclodextrin 的混合產物以紅外線光譜和熱分析儀測定的結果均無包嵌複合體 (inclusion complex) 形成之跡 象，顯示 enoxacin 不易與環糊精形成包嵌複合物，經體外穿皮吸收試驗後證實：添加α-cyclodextrin，β-cyclodextrin，γ-cyclodextrin 對 enoxacin 吸收無顯著的增加或是抑制作用。丙二醇亦呈現相似之結果，無論在通透速率或是延滯時間上。
EDTA 為一種陽離子嵌合劑，在純水溶液中，EDTA 對 enoxacin 之溶解度及穿透速率之促進效果與 EDTA 的濃度呈正比例的相關性，而緩衝溶液中 EDTA 之助溶效果明顯地受到緩衝溶液的影響。
本研究中所得之經皮吸收試驗結果可作為日後開發 enoxacin 經皮輸藥系統之參考，以期對於皮膚或軟組織的感染症提供更佳的療效與便利。

The fluoroquinolones represent an important advance in antimicrobial therapy. They differ significantly in their antimicrobial spectrum of activity and their pharmacokinetic characteristics. In our series studies about quinolone percutaneous aborption properties, enoxacin presented the best permeability characteristics in six quinolones. Therefore, We took a further transdermal research for enoxacin in this experiment.
Enoxacin is an amphillic compound (pka1=6.4, pka2=8.4) , its solubility is affected by pH values of vehicle notably. It is more soluble in acidic or basic solution, but there is a higher partition coefficient in neutral state. The permeation rate of enoxacin is also influenced by the variation in buffer pH values, it is high in pH=3 buffer and low in pH=8 buffer. The flux of enoxacin is enhanced four times through stripped skin than intact skin.
Cationic surfactant (benzalkonium chloride) presented the best enhancing effect no matter what the buffer pH values are. The enhancing factor reached 300 in pH3 BC 1%(w/v) sol'n. Besides, it results in the shorter lag time when benzalkonium chloride is used. In sodium lauryl sulfate solution, enoxacin displayed a different penetration profile with a longer lag time. Flux was decreased in the acidic state and increased in basic state Nonionic surfactants (Tween 80) didn't show any enhancing effect on the percutaneous absorption of enoxacin markly. And the flux was decreased to 1/3 at pH 10 condition.
Increase in β-cyclodextrin (CD) concentrations wo'nt raise the the solubility of enoxacin. There were three kind of melliods to prepare inclusion complex and the products were evaluated by differential scanning calorimetry and IR spectrum. There were no sign to show the inclusion complex formed. It's difficult for enoxacin to form an inclusion complex with β-CD. The permeation properties of enoxacin is not changed by adding α-CD, β-CD, or γ-CD into donor solutin.
EDTA is a kind of chelating agent. Its effects on increasing enoxacin solubility and permeability are EDTA concentration dependent in purified water but altered by buffer system in buffer solution.
The results of in vitro enoxacin percutaneous absorption study offered a foundaion of enoxacin transdermal delivery system. In order to get a better therapeutic efficacy and convenience for skin and soft tissue infections.