ORAL SUBMICRON PARTICLE DELIVERY SYSTEM FOR PROTEINS AND PROCESS FOR ITS PRODUCTION

摘要

The invention provides a novel submicron system for the oral administration of proteins. An effective oral carrier for proteins should shield its content against the gastrointestinal tract proteases and be capable of facilitating the uptake of the protein drug across the gastrointestinal epithelium. The present invention relates to production of gelled particles which comprises a protein drug susceptible to enzymatic degradation by enzymes and acid conditions in the stomach, a polymeric matrix which undergoes precipitation-swelling process, and two-layer-coating materials which are themselves capable of enhancing absorption of said drug across the intestinal mucosal tissues and of inbihiting degradation of said drug by gastric enzymes. Insulin-loaded particles with appropriate submicron size for gastrointestinal absorption were made of natural occurring polymers by emulsification-based method and proved to be gastric pH and protease protective. Effects on glycemia were observed during 14 h after their oral single administration to rats, achieving 42% of pharmacological activity compared to subcutaneous administration. Postprandial rise in blood glucose was suppressed and insulinemia levels increased by a factor of seven. The relative oral bioavailability of insulin calculated over 8 h by comparison with a subcutaneous injection of free insulin was 34%.