経皮経粘膜吸収とＤＤＳ ペプチド性医薬品の経粘膜吸収改善

Abstract

Peptide and protein drugs are becoming a very important class of therapeutic agents. However, the oral bioavailability of peptide and protein drugs is generally poor because they are extensively degraded by proteases in the gastrointestinal tract and impermeable through the intestinal mucosa. For systemic delivery of peptide and protein drugs, parenteral administration is currently required to achieve their therapeutic activities. However, these administration are poorly accepted by patients and may cause allergic reactions and serious side effects. Therefore, various strategies have been examined to overcome the delivery problems of these peptides when they administered orally. These strategies include (1) to use additives such as absorption enhancers and protease inhibitors, (2) to develop an administration method for peptides that can serve as an alternative to oral and injection administration, (3) to modify the molecular structure of peptide and protein drugs to produce prodrugs and analogues, and (4) to use the dosage forms to these peptide drugs. Of all these strategies, we demonstrated that transmucosal absorption of various peptides including insulin, calcitonin, tetragastrin and thyrotropin releasing hormone (TRH) could be improved by using these approaches. Therefore, these approaches may give us basic information to improve the transmucosal absorption of peptide and protein drugs.