IMPROVEMENT OF INTESTINAL-ABSORPTION OF HUMAN CALCITONIN BY CHEMICAL MODIFICATION WITH FATTY-ACIDS - SYNERGISTIC EFFECTS OF ACYLATION AND ABSORPTION ENHANCERS

To improve the intestinal absorption of human calcitonin (hCT), novel lipophilic derivatives of hCT were synthesized by chemical modificatio n with short-chain length fatty acids such as acetic acid and caproic acid, and the intestinal absorption and stability of these derivatives were examined in rats. The intestinal absorption properties of hCT an d its acyl derivatives, acetylated hCT (Ac-hCT) and caproylated hCT (C ap-hCT), were estimated by measuring its hypocalcemic effects. Their i ntestinal absorption and stability in the intestinal mucosal homogenat es were improved by increasing the carbon number of the fatty acid. Fu rthermore, we investigated the effects of co-administered absorption e nhancers, sodium glycocholate (Na-GC), N-lauryl-beta-D-maltoside (LM), sodium deoxycholate (Na-DC) and sodium salicylate (Na-Sal), on the in testinal absorption of hCT and its acyl derivatives. Their intestinal absorption was slightly enhanced by the addition of various absorption enhancers except for Na-Sal. However, the extent of the promoting eff ect was a little higher for a native hCT rather than for acyl-hCT deri vatives. These results suggested that it may be possible to achieve th e further absorption enhancement of hCT by using a combination of acyl ation and absorption enhancers.