- 學位論文
連翹酯苷A注射緩釋劑型之開發及藥物動力學評估
Development, characterization and pharmacokinetics of the extended-release injectable delivery system of forsythoside A
摘要
連翹酯苷A (Forsythoside A)是連翹(Forsythia suspense VAHL.)中的主要活性成分之一，具有抗氧化及抗菌、抗病毒的功能。然而，先前的研究指出，連翹酯苷A在體內的半衰期較短，可能導致較為短暫的作用時間而影響其抗微生物之效果。同時，由於目前已開發之HPLC-UV分析方法靈敏不足，可能會影響藥物動力學實驗結果，因此在本研究中，發展了一個使用高效液相層析儀及電化學偵測器(HPLC-EC)的分析方法以分析連翹酯苷A在大鼠血漿中的濃度，運用於藥物動力學實驗。此分析方法具有良好的線性關係。準確度範圍為94.5-106.5%， 而相對標準差大致皆小於6.6%，表示此分析方法具有良好的準確度及精密度。此外，為了延長連翹酯苷A在體內的循環時間，也發展了一個以泊洛沙姆(Poloxamer) 407為基底的溫度敏感性水凝膠，並添加P188或PEG 6000將其性質做最佳化，使之具有適當的溶液-凝膠轉換溫度、成膠時間及黏度，而有延長釋放的效果。而藥物動力學的實驗結果顯示連翹酯苷A製成水凝膠後，比起以靜脈或皮下注射連翹酯苷A水溶液可顯著的延長其半衰期，而這也表示此溫度敏感性水凝膠劑型可延長連翹酯苷A在體內的循環時間。
並列摘要
Forsythoside A (FSA) is one of the main bioactive ingredients in Forsythia suspense VAHL., which possesses the antioxidant and antibacterial effects. The previous study demonstrated that the half-life of FSA was relatively short, however, indicating the brief therapeutic duration. Also, the previously developed method using high-performance liquid chromatography and ultraviolet-visible detector (HPLC-UV) was not sensitive enough that might affect the result of pharmacokinetic study. In present study, an analytical method using HPLC and electrochemical detector (HPLC-EC) for determination of FSA in rat plasma was developed. Pinoresinol was used as internal standard (IS). The accuracy of this method was ranging from 94.5 to 106.5%, and the intra- and inter-day precision RSD was generally lower than 6.6%, demonstrating good accuracy and precision. Furthermore, a Poloxamer 407 based thermal sensitive hydrogel formulation with addition of P188 or PEG 6000 was optimized and evaluated to extend the circulation time of FSA. The result of pharmacokinetic study showed the half-life of FSA hydrogel was significantly longer as compared with that of FSA solution administrated intravenously and subcutaneously, indicated that the circulation time of FSA was prolonged by temperature-sensitive hydrogel formulation.