Oral delivery of peptides using enzyme-cleavable membrane translocators
AssigneeUnigene Laboratories Inc.
InventorsWilliam Stern, Nozer M. Mehta, Martha V. L. Ray
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Abstract
Bioavailability of peptide active agents to be administered orally is enhanced by a pharmaceutical composition providing targeted release of the peptide to the intestine in addition to having the active peptide linked to a membrane translocator which is capable of being at least partially cleaved in vivo by an enzyme. The composition includes an acid-resistant protective vehicle which transports components of the invention through the stomach and a sufficient amount of a pH-lowering agent to lower local intestinal pH. All components are released together into the intestine with the peptide.
Claims57
A pharmaceutical composition for oral delivery of a physiologically active peptide agent comprising:
- (A) a therapeutically effective amount of said active peptide linked to a membrane translocator, said membrane translocator possesses the capability of being at least partially cleaved from the active peptide in vivo by an enzyme;
- (B) at least one pharmaceutically acceptable pH-lowering agent and/or protease inhibitor;
- and
- (C) an acid resistant protective vehicle effective to transport said pharmaceutical composition through the stomach of a patient while preventing contact between said active peptide agent and stomach proteases.
A method for enhancing the bioavailability of an orally delivered physiologically active peptide agent comprising:
- (A) linking said peptide agent to a membrane translocator that possesses the capability of being at least partially cleaved in vivo by an enzyme;
- and
- (B) selectively releasing said peptide active agent linked to said membrane translocator, together with at least one pH-lowering agent and/or protease inhibitor into a patient's intestine following passage of said peptide active agent, pH-lowering agent and/or protease inhibitor through said patient's mouth and stomach under protection of an acid resistant protective vehicle which substantially prevents contact between stomach proteases and said peptide agent.
Dependencies are inferred from the claim text.