Methods and Compositions for Oral Administration of Exenatide

Abstract

This invention provides compositions comprising a byetta, fish oil, and a protease inhibitor, method for treating diabetes mellitus, comprising administering same, and methods for oral or rectal administration of a byetta.

1 - 11 . (canceled) 
     
     
         12 . A method for administration of exenatide to a subject, comprising rectally administering, to the subject, a pharmaceutical composition comprising the exenatide, a protease inhibitor selected from Soybean Trypsin Inhibitor (SBTI) and aprotinin, EDTA, and an omega-3 fatty acid;
 wherein the pharmaceutical composition does not comprise both SBTI and aprotinin; and   wherein a substantial fraction of the exenatide retains glucagon-like peptide-1 (GLP-1) agonist activity after absorption through a rectal tissue of the subject.   
     
     
         13 . The method of  claim 12 , wherein the pharmaceutical composition is in the form of a suppository. 
     
     
         14 . The method of  claim 13 , wherein the suppository is a solid suppository. 
     
     
         15 . The method of  claim 14 , wherein the solid suppository comprises a base of solid fat that becomes flowable within the rectum. 
     
     
         16 . The method of  claim 13 , wherein the suppository is a gelatin capsule suppository that comprises a substance that is liquid at room temperature. 
     
     
         17 . The method of  claim 12 , wherein the subject is obese. 
     
     
         18 . The method of  claim 12 , wherein the administration lowers plasma glucagon in the subject. 
     
     
         19 - 23 . (canceled) 
     
     
         24 . A method for treating diabetes mellitus in a diabetic subject, comprising rectally administering, to the subject, a pharmaceutical composition comprising exenatide, a protease inhibitor selected from Soybean Trypsin Inhibitor (SBTI) and aprotinin, EDTA, and an omega-3 fatty acid, thereby treating the diabetes mellitus in the subject;
 wherein the pharmaceutical composition does not comprise both SBTI and aprotinin; and   wherein a substantial fraction of the exenatide retains glucagon-like peptide-1 (GLP-1) agonist activity after absorption through a rectal tissue of the subject.   
     
     
         25 . The method of  claim 24 , wherein the pharmaceutical composition is in the form of a suppository. 
     
     
         26 . The method of  claim 25 , wherein the suppository is a solid suppository. 
     
     
         27 . The method of  claim 26 , wherein the solid suppository comprises a base of solid fat that becomes flowable within the rectum. 
     
     
         28 . The method of  claim 25 , wherein the suppository is a gelatin capsule suppository that comprises a substance that is liquid at room temperature. 
     
     
         29 . The method of  claim 24 , wherein the subject is obese. 
     
     
         30 . The method of  claim 24 , wherein the administration lowers plasma glucagon in the subject. 
     
     
         31 - 71 . (canceled) 
     
     
         72 . The method of  claim 12 , wherein the amino acid sequence of the exenatide has at least 95% sequence identity to HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS (SEQ ID NO:1) and has glucagon-like peptide (GLP-1) agonist activity. 
     
     
         73 . The method of  claim 72 , wherein the amino acid sequence of the exenatide is the sequence of SEQ ID NO:1. 
     
     
         74 . The method of  claim 24 , wherein the amino acid sequence of the exenatide has at least 95% sequence identity to HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS (SEQ ID NO:1) and has glucagon-like peptide (GLP-1) agonist activity. 
     
     
         75 . The method of  claim 74 , wherein the amino acid sequence of the exenatide is the sequence of SEQ ID NO:1.