口服不同劑型valsartan對自發性高血壓大鼠的降血壓影響

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Title:	口服不同劑型valsartan對自發性高血壓大鼠的降血壓影響 Blood pressure-lowering effects of different dosage forms of orally administered valsartan on spontaneously hypertensive rats
Authors:	徐士恩
Contributors:	藥學系林千玉
Keywords:	新型人造油體複合溶劑高血壓大鼠纈沙坦 valsartan composite solvent hypertensive rat new artificial oil body
Date:	2017
Issue Date:	2018-01-11 11:44:32 (UTC+8)
Abstract:	高血壓為國人心血管疾病的危險因子，其臨床治療的第一線用藥valsartan(纈沙坦)，是一種血管緊張素II受體阻斷劑（angiotensin II receptor blocker），不容易溶於水。前人研究已有數種改善低溶解度的方法，其中也有進一步證實溶解度改善後，確實能增加動物口服valsartan的血中濃度，然而，卻未能證明對高血壓動物的降血壓影響。因此本研究的目的有二：一是尋找一種溶解度更高的配方，以期更能增加生體可利用率；二是以此配方製作不同劑型，觀察對自發性高血壓大鼠的降血壓影響是否不同。實驗方法是將數種可以溶解valsartan的溶劑混合為複合溶劑，找到能提高valsartan最大溶解度的配方後，再以此配方製成不同劑型，分別餵食自發性高血壓大鼠，以非侵入性血壓機量測血壓。結果顯示，使用特定配方的複合溶劑可大為提高valsartan溶解度，約為前人研究的2000倍以上；且此複合溶劑的不同劑型，對自發性高血壓大鼠的降血壓效果並不相同，其中以新型人造油體劑型的降血壓效果最佳。綜合上述，本研究已找到valsartan溶解度更高之配方，此配方的新型人造油體劑型更能達到降血壓效果，未來或許可提供治療高血壓患者口服valsartan，解決其低溶解度與低生體可利用率的方法之一。 Hypertension is a risk factor for cardiovascular disease in Taiwan, the first line of its clinical treatment, valsartan, which is an angiotensin II receptor blocker and not easily soluble in water. Previous studies have found several methods to improve valsartan’s low solubility, and were further improved that it could increase the valsartan concentration in blood of animal's studies. However, there is no any experiment to demonstrate the blood pressure-lowering effect on hypertensive animals. Therefore, the purpose of this study has two aspects. First, to find a formula that can dissolve more valsartan in solvents and increase the higher bioavailability. Second, to produce different dosage forms in the same formula to apply in hypertensive rats, and observe whether there are different blood pressure-lowering effects. The method is mixing several kinds of solvents which can dissolve valsartan to form the composite solvent. The composite solvent is a specific formula that has the maximum solubility of valsartan. We then make the different dosage forms of the specific formula. Each of the different dosage forms was fed hypertensive rats. The blood pressure of the hypertensive rat was measured by the non-invasive measuring machine. The results show that the composite solvent greatly increase the solubility of valsartan more than 2,000 times of previous studies. The different dosage forms of the composite solvent have different effects of lowering blood pressure on the hypertensive rats. The dosage form of the new artificial oil body works best. In conclusion, this study has found a higher solubility formula for valsartan, and a new dosage form of the artificial oil body achieving a better blood pressure-lowering effect. It may provide one of the treatment to solve the low solubility and bioavailability of orally administered valsartan for the hypertensive patients.
Relation:	電子全文公開日期：2022-07-29，學年度：105，102頁
Appears in Collections:	[Dept. of Pharmacy] Dissertations and Theses

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