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Summary  Water-in-oil-in-water (W/O/W) insulin emulsions with a concentration of 100 U/ml of insulin were prepared, and the possible absorption of insulin in emulsion form was examined. The following results were obtained: W/O/W insulin emulsions were quite resistant to proteolytic enzymes in vitro. In the presence of pancreatic lipase, however, W/O/W insulin emulsion gradually lost its activity by the action of proteolytic enzymes. When administered to the jejunum at doses over 10 U/kg, a significant and consistent increase in plasma insulin was observed, followed by a fall in blood glucose. The infusion of W/O/W insulin emulsions into the jejunum was three to four times more effective than the administration of aqueous insulin. Insulin, when administered to the stomach, did not cause hypoglycemia at doses up to 150 U/kg. When W/O/W insulin emulsions were administered orally, on the other hand, definite responses were observed in 3 out of 7 rabbits with 100 U/kg and in 4 out of 7 rabbits with 150 U/kg. For developing an effective method for oral administration of insulin, the present results indicate a possible means of protecting insulin molecule from proteolytic destruction, and of facilitating intestinal absorption of insulin.

Enteral absorption of water-in-oil-in-water insulin emulsions in rabbits