Purpose: To investigate the behaviour of peptides and hyaluronan in strong acid solutions containing electrolytes in the preparation of a new formulation of insulin, hyaluronan-insulin complex, and to evaluate the in vivo oral activity of the formulation.
Methods: Individual processing parameters in the preparation of the insulin complex were first refined, and two formulations were subsequently investigated. The chemical structure, particle size and hydrophilic/hydrophobic properties of the insulin complex in these formulations were studied using light scattering techniques, amino acid analysis, atomic force microscopy and cryo-transmission electron microscopy. The in vivo activity of oral hyaluronan-insulin complex was then evaluated by measuring the decrease in blood glucose concentrations in streptozotocin diabetic rats.
Results: Five of seven batches of the two insulin complex formulations fit the baseline criteria for approval of the new formulation. The formulation consists of a transparent aqua sol containing a solid hydrophobic phase as precipitate. Glucose-lowering activity was demonstrated after oral administration of the insulin complex'to diabetic rats.
Conclusion: A new insulin formulation, a hyaluronan-insulin complex, has been developed and oral activity has been demonstrated.