Takeichi Y, Baba K, Kinouchi Y, Iida Y, Umeno Y, Muranishi S, Nakai Y
Pharmaceutical Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Chem Pharm Bull (Tokyo). 1990 Sep;38(9):2547-51. doi: 10.1248/cpb.38.2547.
An improvement of the rectal absorption of uracil was examined by the application of absorption enhancers in addition to the increased solubility of uracil. Uracil was ground with additives such as MgO, sodium 2,6-dihydroxybenzoate, human serum albumin or hydroxypropylmethylcellulose acetate succinate. Aqueous, oily and powdery formulations, which consisted of the ground mixtures, nicotinamide, urea and absorption enhancers such as polyoxyethylene (23) cetylether (BC-23) or sodium caprate, were prepared. Uracil solubility in the aqueous formulations was increased about 4-13 times that in the corresponding control formulations. When rectally administered to beagle dogs, marked increases in the plasma uracil level were observed in some of the cases of aqueous and oily formulations. In the powdery formulations and formulations containing macromolecular additives, however, absorption improvements was not observed. The results indicated that an improvement in the absorption of uracil was caused by the combinative improving effect of the increased uracil solubility and the promoting effect of absorption enhancers.
除了提高尿嘧啶的溶解度外，还通过应用吸收促进剂来研究尿嘧啶直肠吸收的改善情况。将尿嘧啶与氧化镁、2,6 - 二羟基苯甲酸钠、人血清白蛋白或醋酸琥珀酸羟丙基甲基纤维素等添加剂研磨。制备了由研磨后的混合物、烟酰胺、尿素和吸收促进剂如聚氧乙烯（23）十六烷基醚（BC - 23）或癸酸钠组成的水性、油性和粉末状制剂。尿嘧啶在水性制剂中的溶解度比相应对照制剂提高了约4 - 13倍。当对比格犬进行直肠给药时，在一些水性和油性制剂的情况下观察到血浆尿嘧啶水平显著升高。然而，在粉末状制剂和含有大分子添加剂的制剂中，未观察到吸收改善。结果表明，尿嘧啶吸收的改善是由尿嘧啶溶解度增加的联合改善作用和吸收促进剂的促进作用引起的。
