萊克多巴胺屬乙型腎上腺素受體促進劑類藥物,因具有提高飼料換肉率及減少排泄物等效果,常用為動物飼料添加物,但在台灣列為禁用之藥物。環糊精與型腎上腺素受體促進劑形成內包複合物具有提高光譜特性,具備控制釋放功能及提高分解效率等應用。本研究透過紫外/可見光分光光譜儀、螢光光譜儀及核磁共振光譜儀比較分析萊克多巴胺與α-CD、β-CD、γ-CD三種環糊精形成內包複合物之作用機制。結果顯示,導入環糊精能使萊克多巴胺的紫外線吸收度及螢光強度產生增強效果,其中以β-CD增色幅度最為明顯。螢光消光實驗進一步顯示β-CD與萊克多巴形成之複合物呈現最低之消光效果。核磁共振氫譜 DOSY 實驗測定萊克多巴胺與三種不同環糊精混合時的擴散係數(DS)並據以計算而得之結合常數(Ka) 顯示萊克多巴胺與環β-CD糊精間能形成最穩定之複合物,空腔尺寸扮演重要。NOESY 實驗結果及以NOE強度研衍生之距離限制進行分子模擬結果呈現萊克多巴胺 H-8、H-9側苯環區進入 β-CD 空腔。疏水性為形成內包複合物之主要驅動力。
Ractopamine is a β2-adrenergic receptor agonist. It is a common feed additive supplement to increase the feed conversion rate and to decrease the animal excrements. Ractopamine is banned in Taiwan due to its suspected health effects. The formation of inclusion complex between β-agonist drugs and cyclo-dextrins could enhance the spectroscopic features of guest drugs, provide the control-releasing function and promote the degrade of drugs. In this study, we use UV-Vis spectroscopy, fluorescence spectroscopy and NMR spectroscopy to investigate the interaction between ractopamine and three cyclo-dextrins. The results showed that with the introduction of cyclo-dextrins into ractopamine solution, both UV –Vis absorption in and fluorescence intensity of ractopamine increased. Among them, β-dextrin results in the most obvious change. The binding constants of ractopamine obtained from the diffusion coefficients measured from NMR DOSY experiments showed that, the drug formed the most stable complex with β-dextrin. These results showed that the size of cyclo-dextrin is a critical parameter in the formation of the complex. The molecular simulation based on the distance constraints derived from the NOE in NMR NOESY experiments indicated that the H-8、H-9 in the non-polar side of ractopamine entered the cavity of β-dextrin. Hydrophobicity is the major driving force in the formation of inclusion complex.