七代茶鹼醋酸衍生物之鹼與酶水解及其物化性質   全文下載

Alkaline, Enzymatic Hydrolysis and Physicochemical Properties of 7-Theophyllineacetic Acid Derivatives

本研究製備出一系列七代茶鹼醋酸的二醇酯類衍生物，這些衍生物的穩定性在60℃的氫氧化納溶液（pH 13.0）中進行測定。此降解反應的進行以高效能液相層析儀配合紫外光偵測器檢測。所有衍生物都被水解，其速率常數也被計算出來。此一化學水解為一級速率反應，其半衰期亦被決定。本研究亦討論了這些酯類衍生物在稀釋的人類血漿（37℃）中的釋出程度，在此環境下，這些衍生物具有高度穩定性，在24小時高效能液相層析儀的觀察下，並未觀察到自發性的水解產物產生。這些七代茶鹼醋酸及其酯類衍生物的親水率跟親脂率（以log P表示）也利用紫外光光譜加以研究。與原化合物相比較，所有的酯類衍生物表現出較高的親脂率，然其在水性基質中，溶解度則相對降低。

In the present study, a number of esters which derived from 7-theophyllineacetic acid were prepared. The stability of 7-theophyllinylacetyloxyglycols was evaluated in sodium hydroxide solution (pH 13.0) at 60ûC. The degradation reaction was monitored by using a HPLC assay with ultraviolet detection. All of esters were hydrolyzed to yield the correspondence quantitative amount of the hydrolytic product. The rate constants of the hydrolytic decomposition of the described esters were estimated. The chemical mediated conversion displayed first-order kinetics, and half-lives of hydrolysis were determined, too. Also, the ability of the esters to release 7- theophyllineacetic acid through diluted human plasma at 37ûC was studied. Compounds were found to possess a high stability at these conditions. It was noticed that no spontaneous hydrolysis of ester derivatives was noticed within 24 hr as revealed by HPLC analysis. The aqueous solubility and lipophilicity (expressed as logP) of 7-theophyllineacetic acid and its esters were investigated by means of UV spectrophotometry. It was found that all of the esters were more lipophilic than its parent molecule. However, their solubility in aqueous media was decreased, compared by the parent drug. 本研究製備出一系列七代茶鹼醋酸的二醇酯類衍生物，這些衍生物的穩定性在60℃的氫氧化納溶液（pH 13.0）中進行測定。此降解反應的進行以高效能液相層析儀配合紫外光偵測器檢測。所有衍生物都被水解，其速率常數也被計算出來。此一化學水解為一級速率反應，其半衰期亦被決定。本研究亦討論了這些酯類衍生物在稀釋的人類血漿（37℃）中的釋出程度，在此環境下，這些衍生物具有高度穩定性，在24小時高效能液相層析儀的觀察下，並未觀察到自發性的水解產物產生。這些七代茶鹼醋酸及其酯類衍生物的親水率跟親脂率（以log P表示）也利用紫外光光譜加以研究。與原化合物相比較，所有的酯類衍生物表現出較高的親脂率，然其在水性基質中，溶解度則相對降低。