Matsuzawa A, Morishita M, Takayama K, Nagai T
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
Biol Pharm Bull. 1995 Dec;18(12):1718-23. doi: 10.1248/bpb.18.1718.
The present work was undertaken to prepare water-in-oil-in-water (W/O/W) emulsions as a carrier for insulin via the enteral route. The emulsions were prepared by a two-step procedure using a homogenizer. To avoid insulin escape from the inner aqueous phase, 3, 5, or 10% gelatin was added in the inner phase. The oily phase was composed of 5% lecithin, 20% Span 80 and 75% soybean oil. The purified water containing 3% Tween 80 was used for the outer aqueous phase. In addition, these emulsions were filtered with a membrane filter (0.45 micron) to obtain smaller emulsion particles. The stability of the emulsions was evaluated by a turbidity measurement method and photomicrographic observation. By the addition of gelatin to the inner aqueous phase and storage at 4 degrees C, the stability of the emulsions could be improved. The hypoglycemic effects of insulin after administration of emulsion to the stomach, the duodenum, the jejunum, the ileum and the colon were examined using an in situ loop method in rats. A significant hypoglycemic effect was observed at the ileum and colon loops after administration of the filtered emulsions containing 5% gelatin in the inner phase. These findings suggest that the W/O/W multiple emulsions stabilized by gelatin can improve ileal and colonic absorption of insulin.
本研究旨在制备水包油包水（W/O/W）型乳剂，作为胰岛素经肠道给药的载体。采用两步法，使用均质机制备乳剂。为避免胰岛素从内水相逸出，在内相中加入3%、5%或10%的明胶。油相由5%的卵磷脂、20%的司盘80和75%的大豆油组成。含有3%吐温80的纯化水用于外水相。此外，这些乳剂用膜过滤器（0.45微米）过滤以获得更小的乳剂颗粒。通过浊度测量法和显微摄影观察评估乳剂的稳定性。通过向内水相中添加明胶并在4℃下储存，可以提高乳剂的稳定性。使用大鼠原位肠袢法，研究了将乳剂分别给予胃、十二指肠、空肠、回肠和结肠后胰岛素的降血糖作用。在内相中含有5%明胶的过滤乳剂给药后，在回肠和结肠肠袢处观察到显著的降血糖作用。这些发现表明，由明胶稳定的W/O/W多重乳剂可以改善胰岛素在回肠和结肠的吸收。
