アシル化修飾を利用したペプチド性医薬品の消化管吸収の改善

抄録

Generally, the oral absorption of peptide and protein drugs is typically poor. This has been attributed to their extensive hydrolysis and poor membrane permeability characteristics. To overcome these delivery problems, we synthesized lipophific derivatives of peptides and proteins such as tetragastrin, insulin, human calcitonin and lysozyme by chemical modification with various fatty acids. A significant increase in the intestinal absorption of these lipophilic peptides was observed in comparison with native peptides. In addition, these derivatives were more stable than the parent peptides in homogenates of the various intestinal mucosae Furthermore, the mechanisms whereby intestinal absorption and stability of these peptides was improved by acylation were discussed in this review article. In summary, this chemical modification approach may be useful to improve the intestinai absorption of peptides and proteins.