Development of oral insulin: progress and current status.

摘要

NOBEX oral drug delivery technology is centered on modification of peptides, proteins and small organic molecules by attachment of one or more amphiphilic oligomers. Attachment of these oligomers results in stability to enzymatic degradation, improved solubility to allow optimized formulation, and modification of pharmacology to prolong circulating half-life and activity. NOBEX has applied this technology to insulin, creating an orally absorbed, bioactive conjugate which is safe and rapidly absorbed and which demonstrates dose-dependent, glucose-lowering effects in animal models, healthy volunteers and type 1 diabetic patients. Results of recently completed and ongoing studies in both type 1 and type 2 diabetes suggest a promising role for conjugated insulin in the management of fasting and post-prandial hyperglycemia. Orally administered conjugated insulin is delivered first to the liver through the portal circulation, similar to the physiological route of insulin secretion in non-diabetic individuals. Potential benefits from this route of insulin delivery include improved disease management and reduction of long-term complications of diabetes. Further studies with oral conjugated insulin are planned in both type 1 and type 2 diabetic patients.