去甲氧基姜黄素羟丙基-β-环糊精磷脂复合物在大鼠体内药动学研究

Pharmacokinetics study of deme-thoxycurcumin hydroxypropyl-β-cyclodextrin phospholipid complex in rats

目的比较去甲氧基姜黄素羟丙基-β-环糊精磷脂复合物、去甲氧基姜黄素羟丙基-β-环糊精包合物、去甲氧基姜黄素磷脂复合物、去甲氧基姜黄素原料药在大鼠体内的药代学性质,探讨去甲氧基姜黄素羟丙基-β-环糊精磷脂复合物作为药物载体的优势。方法 SD大鼠灌胃给药50mg/mL(以去甲氧基姜黄素原料药计)剂量制剂及游离药物后,分别于5min、10min、15min、30min、45min、1h、1.5h、2h、3h、4h、6h、8h、10h、12h、1d、2d、3d在大鼠眼底静脉丛取血。采用高效液相法测定血浆中去甲氧基姜黄素的浓度。结果去甲氧基姜黄素羟丙基-β-环糊精磷脂复合物的AUC0-∞(μg·L-1·h)为(1 424.87±258.62),较原料药去甲氧基姜黄素(370.58±2.76)、去甲氧基姜黄素磷脂复合物(716.17±123.18)、去甲氧基姜黄素羟丙基-β-环糊精包合物(1 009.35±138.64)均有提高(P<0.01或P<0.05)。结论去甲氧基姜黄素羟丙基-β-环糊精磷脂复合物较单一的磷脂复合物或羟丙基-β-环糊精包合物更能促进药物的吸收,有利于提高药物的生物利用度。

Objective To compare the pharmacokinetics of deme-thoxycurcumin hydroxypropyl-β-cyclodextrin phospholipid complex, deme-thoxycurcumin hydroxypropyl-β-cyclodextrin, deme-thoxycurcumin phospholipid complex and deme-thoxycurcumin in rats in vIvo, so as to discuss the advantages of hydroxypropyl-β-cyclodextrin phospholipid complex as drug carrier. Methods SD rats were gavaged with the preparations and free drug at 50 mg/mL （dose according to deme- thoxycurcumin）, Then, blood samples were drawn from rat retinal venous plexus at 5 min, 10 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 1 d, 2 d and 3 d. And the deme-thoxycurcumin concentrations in blood were determined by HPLC, Results The AUC0-∞ of deme-thoxycurcumin hydroxypropyl-β-cyclodextrin phospholipid complex was （1 424.87±258. 62） μg. L-1. h, which was higher than that of deme-thoxycurcumin （370.58±2.76） μg. L-1. h, deme- thoxycurcumin phospholipid complex （716. 17± 123. 18） μg . L -1 . h and deme-thoxycurcumin hydroxypropyl-β-cyclodextrin 〈1 009. 35± 138. 64） μg . L-1 . h, being 3. 84, 1. 98, and l. 41 folds of deme-thoxycurcumin, deme-thoxycurcumin phospholipid complex and deme-thoxycurcumin hydroxypropyl-β-cyclodextrin, respectively （P〈0. 01 or P〈0. 05）. Conclusion The deme-thoxycurcumin hydroxypropyl-β-cyclodextrin phospholipid complex has a better absorption property than deme- thoxycurcumin phospholipid complex and deme-thoxycurcumin hydroxypropyl-β-cyclodextrin, which can help to improve the bioavailability.