| 摘要: | 厚朴酚（magnolol）為一水難溶性之多酚類，從木蘭科植物厚朴 Magnolia officinalis 之莖皮、根皮及枝皮所分離出的成分，具有抗氧化、抗發炎、抗腫瘤、抗菌、抗氣喘、心臟保護作用及胃腸道保護作用等優越的藥理活性。然生體可用率低，本研究擬採用固體分散的技術，來增加厚朴酚之水中溶解度及體外溶離率，以期提高口服吸收。
首先採用多種增溶劑測試其於水中對厚朴酚之增溶作用，結果顯示普維酮K-30及HP-β-環糊精等具有顯著的效果。故本研究即選用普維酮K-30及HP-β-環糊精為載體，以熱熔法或溶媒蒸散法製成固體分散物，再經示差掃描熱分析、傅式轉換紅外線光譜分析、粉末X光繞射分析及電子顯微鏡掃描分析，得知在適當比例下，厚朴酚可與此兩種載體形成非晶形的產物，但由體外溶離試驗的比較，則顯現普維酮K-30之固體分散物之溶離效果較好。另在紐西蘭白兔之口服吸收比較上，在血峰濃度（Cmax）及血藥面積（AUC）方面，此固體分散物比單獨厚朴酚分別增加45％及83％，確實可顯著地提高生體可用率。
本研究中發現熱熔法比溶媒蒸散法更易形成非晶形之厚朴酚固體分散物，且熱熔法兼具便利、簡單、經濟、環保等優點，因此可提供業界將來欲開發厚朴酚為口服劑型時之參考。
Magnolol, a water-insoluble polyphenol, were isolated from Magnolia officinalis and reported to possess many beneficial pharmacological activities including anti-oxidation, anti-inflammatory, anti-thrombus, anti-carcinogenic, antibacterial and protecting gastro-intestinal tract. However, its oral absorption is poor and erratic that many offend its efficiency. In this paper, we attempted to enhance the solubility and dissolution of magnolol by the formation of amorphous solid dispersionwith water-solable carrier and thereby could tried to render its utilization in oral absorption more efficient in clinic.
Among of the investigated carries, povidone K-30 and HP-β-cyclodextrin were found to have significant solubility enhancing effect on the magnolol. Therefore, the solid dispersions （SD） of magnolol were prepared by comelting or solvent evaporating method with povidone K-30 or HP-β-cyclodextrin and the characterization of the SD were assessed by the differential scanning calorimetry, Fourier transformation infrared spectrophotometry, powder X-ray diffraction and scanning electron microscopy. It was found that the solid dispersion would be an amorphous when the sufficient amount of carrier was used.
The SD prepared from the povidone K-30 was found having the best dissolution rate than that of prepared from HP-β-cyclodextrin or the intact drug. The pharmacokinetics of oral absorption of magnolol in rabbits were also significantly enhanced ( 45％ in Cmax or 83％ in AUC, respectively) when the SD was administered to compared with the intact drug.
In this study, we had found that the comelting methond was easier to form the amorphous amagnolol solid dispersion than the solvent evaporating method. On the other hand, the former also had the benefits of being feasible, economic, safety and environmental protection. In practice, if the oral solid dosage form of magnolol would be expected to have more efficiency, this proposed method was worthy of paying more attention to refer. |
