| 摘要: | 柚皮苷元 (Naringenin) 為一難溶於水之黃酮類，存在於如柑橘屬等植物之果實中，體外研究顯示其具有抗氧化、抑制乳房腫瘤細胞增生及延緩發生、抗動脈粥狀硬化、抗潰瘍、及抗血栓等多種優越之藥理活性。然柚皮苷元之生體可用率低，推測其原因可能和低溶解度有關，故本研究擬以固體分散技術來製備柚皮苷元之固體分散物，期能增加柚皮苷元之溶解度及溶離速率，進而增加其口服吸收。
首先選用多種增溶劑測試其在水中對柚皮苷元之增溶作用，結果顯示普維酮等有優異的增溶效果。隨後將柚皮苷元與普維酮以溶劑法或研磨法製備成固體分散物，並經示差掃瞄熱分析、傅式轉換紅外線光譜及粉末X光繞射法驗證，得知在等量柚皮苷元與普維酮共存時，兩種製備方法都可以得到安定性良好的非晶形產物。而由體外溶離試驗及米格魯獵兔犬口服吸收之藥動學比較，顯示出此等固體分散物確實改善了柚皮苷元之溶離度及增加了口服之生體可用率。其中又以研磨法更佳，因其兼具簡便、安全、經濟、環保等特點，值得業界將來欲將柚皮苷元開發成口服劑型時之參考。
Naringenin, a natural flavonoid, is slightly soluble in water and is widely present in Citrus fruits. It was reported to possess many beneficial pharmacological activities including anti-oxidation, inhibiting breast tumour cell''s hyperplasia and delaying occurrence, anti-scleratheroma, anti-uceration as well as anti-thrombus, etc.. However, the oral bioavailability of naringenin is poor, inferring to its low solubility. Therefore, the aim of this study was to prepare the solid dispersion of naringenin, and thus to enhance its solubility and dissolution rate, and then the oral absorption of naringenin could be improved thereby.
From the investigation of the solubilization effect of several kinds of solubilizer, povidone was the first-choice promising carrier. Therefore, the solid dispersions (SD) of naringenin with povidone were prepared by solvent or grinding method. Assessing by the differential scanning calorimetry, Fourier transformation infrared spectrophotometry and powder x-ray diffraction, it was shown that all of SD products would be amorphous when the weight ratio of povidone in it was exceeding 50﹪.
By comparison of the in vitro dissolution tests and the pharmacokinetics in beagles of naringenin, it could be confirmed that both of the preparation methods were actually feasible. However, the grinding method (by ball mill) have the simple, conventient, safe, ecomomic and eco-awareness’s prdominance in practice. It could be suggested that this method be worthy of referring to the manufacturing plant for the development of the oral dosage form of naringenin in clinical use in the furture. |
