Brewster M E, Estes K S, Loftsson T, Perchalski R, Derendorf H, Mullersman G, Bodor N
Center for Drug Design and Delivery, College of Pharmacy, J. Hillis Miller Health Center, University of Florida, Gainesville 32610.
J Pharm Sci. 1988 Nov;77(11):981-5. doi: 10.1002/jps.2600771118.
A dihydropyridine in equilibrium pyridinium salt chemical delivery system (CDS) for estradiol (E2CDS) was complexed with various modified beta-cyclodextrins including hydroxyethyl-beta-cyclodextrin (HECD), hydroxypropyl-beta-cyclodextrin (HPCD), and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DMCD). Complex formation with all of these cyclodextrins resulted in dramatic increases in the water solubility of E2CDS. Studies on the complex of E2CDS and HPCD (E2CDS-CD) indicated that the encapsulated estrogen was approximately four times more stable than the unmanipulated CDS, producing an estimated half-life of degradation of 4 years compared with 1.2 years for the uncomplexed drug at room temperature. The complexation of E2CDS and HPCD also stabilized the dihydronicotinate in solutions containing potassium ferricyanide. This formulation was shown to be equivalent to E2CDS in dimethyl sulfoxide in delivering the oxidized, estradiol precursor (E2Q+) to the brain, and also produced similar biological responses; these included decreased luteinizing hormone (LH) secretion and a decrease in the rate of weight gain in castrated female rats.
一种用于雌二醇的二氢吡啶处于平衡吡啶鎓盐化学传递系统（CDS）（E2CDS）与多种改性β-环糊精复合，包括羟乙基-β-环糊精（HECD）、羟丙基-β-环糊精（HPCD）和七（2,6-二-O-甲基）-β-环糊精（DMCD）。与所有这些环糊精形成复合物导致E2CDS的水溶性显著增加。对E2CDS与HPCD的复合物（E2CDS-CD）的研究表明，包封的雌激素比未处理的CDS稳定约四倍，在室温下估计降解半衰期为4年，而未复合药物的半衰期为1.2年。E2CDS与HPCD的复合还使含有铁氰化钾的溶液中的二氢烟酸盐稳定。该制剂在将氧化的雌二醇前体（E2Q+）递送至大脑方面显示与二甲基亚砜中的E2CDS相当，并且还产生类似的生物学反应；这些反应包括促黄体生成素（LH）分泌减少以及去势雌性大鼠体重增加速率降低。
