Novel pepsin inhibitors attachable to polymer matrices-auxiliary agents for the peroral application of peptide and protein drugs

摘要

(Poly)peptide drugs are commonly administered by parenteral routes broadly recognized as difficult, painful and occasionally dangerous. The need for novel systems achieivng an effective peroral delivery of peptide and protein drugs is a great challenge in pharmaceutical technology. The combination of a bioadhesive polymer with an enzyme inhibitor formes the basis for a efficient delivery system. The polymer matrix is able to enhance the bioavailability of therapeutic agents by a prolonged residence time and an optimal contact with the absorbing surface. The enzyme inhibitor can provide a protective effect from luminal proteolytic inactivation. Though, systemic side effects cannot be excluded caused by absorption of the enzyme inhibitor. In order to prevent these probably severe toxic effects, the inhibitor is coavlently attached to the polymer matrix. Moreover, a sufficient concentration of the inhibitor is thereby ensured guaranteeing an inactivation of proteases penetrating into the polymeric carrier system.~1,2