柚皮? (naringin) 為一水難溶之雙氫黃酮類配醣體，體外研究顯示具多種優越之藥理活性。本研究利用溶媒再結晶法製備不同晶形之柚皮?，經粉末X光繞射法及示差掃瞄熱分析法以觀察晶形差異，得到柚皮?之二種不同晶形。 添加羧甲基纖維素鈉可增加柚皮?之溶解度，並得以製成安定的溶液劑。在柚皮?與羧甲基纖維素鈉之固體混合物中，以示差掃瞄熱分析法可觀察出二者間有明顯的交互作用，經以溶媒蒸散法可得到柚皮?之非晶形固體分散物。 為探討可提高柚皮?生可用率之最佳劑型，將柚皮?懸液、膠體及柚皮?與羧甲基纖維素鈉形成之溶液劑或其固體分散物之膠囊劑分別以200 mg/kg經口投予紐西蘭白兔，比較此四種劑型吸收之差異，結果血清中皆未檢出原型柚皮?及其?元 (naringenin)。而血清中柚皮?代謝物之測定係分別以 b-glucuronidase及sulfatase，於37℃且添加抗壞血酸下水解，以高效液相層析法定量。Naringenin sulfates之血峰濃度與血藥面積皆明顯高於naringenin glucuronides。口服柚皮?-羧甲基纖維素鈉溶液劑其吸收比柚皮?懸液顯著提高了97.2 %，而固體分散物之膠囊劑則幾無吸收。 環孢靈為一治療指數極低之免疫抑制劑。為了解柑橘屬中藥對環孢靈動力學之影響，本研究乃以大白鼠為模型探討單服新劑型Neoral®與分別併服枳實、枳殼、化橘紅後環孢靈體內動力學之差異。血中環孢靈濃度利用螢光偏極免疫法定量。併服枳實之環孢靈血峰濃度與血藥面積分別降低了91.5 % 及95.7 %，而併服化橘紅卻分別增高了47.3 % 及 173.1 %，而併服枳殼時則無明顯改變。為了用藥安全與療效之考量，移植病患服用Neoral®者應避免與枳實、化橘紅併服。; Naringin is a flavonoid possessing many beneficial pharmacological activities but sparingly soluble in water. Crystallization method is used for the preparation of different crystal forms of naringin by using various solvents. Powder X-ray diffraction and differential scanning calorimetry (DSC) demonstrated that two crystal forms of naringin were obtained. Sodium carboxymethylcellulose (CMC) was used to improve the solubility of naringin. Through DSC analysis, significantly interaction of physical mixture was observed. CMC was selected as the carrier of solid dispersion and amorphous product was formed by solvent evaporation method. Four dosage forms of naringin including suspension, colloid, solution of naringin—CMC and capsule of its solid dispersion were orally administered to rabbits (200 mg/kg), respectively, to investigate the improvement of naringin absorption. Naringenin was determined by HPLC after incubation with b-glucuronidase and sulfatase, respectively at 37 ℃ in the presence of ascorbic acid. Significantly more naringenin sulfatate were detected as compared to glucuronides. The absorption was significantly improved by 97.2 % and 17.9 % after oral dosing naringin—CMC solution when compared to those after suspension and colloid of naringin, respectively. Neoral® (cyclosporin) is a potent immunosuppressive agent with narrow therapeutic range. In this study, the effects of Citrus decoctions of Zhishi (Citrus aurantium LINN.), Zhiqiao (Citrus aurantium LINN.) and Huajuhong (Citrus paradisi MACF.) on cyclosporin pharmacokinetics were investigated in rats. Blood samples were assayed for cyclosporin by a specific monoclonal FPIA method. The Cmax and AUC0-t of cyclosporin decreased by 91.5 % and 95.7 % after coadministration with Zhishi decoctions, whereas increased by 47.3 % and 173.1 % after coadministration with Huajuhong decoctions, respectively. However, no significant effect was observed for Zhiqiao decoction. It seems prudent to attend organ allograft recipients treated with Neoral® to avoid the concurrent use of herbal remedies containing Zhishi or Huajuhong.
