Compositions for treatment with glucagon-like peptide, and methods of making and using the same

Abstract

In part, the present invention is directed to compositions comprising a carrier with a metal binding domain, a metal ion, and GLP-1.

1 . A biocompatible composition comprising: a carrier with a metal binding domain (MBD), a metal ion chelated to the metal binding domain of the carrier, and glucagon-like peptide-1 (GLP-1) with a MBD chelated to the metal ion, wherein after administration of the composition to a patient, GLP-1 is released from the carrier.  
     
     
         2 . The composition of  claim 1 , wherein the carrier is one of the following: polymer, micelle, reverse micelle, liposome, emulsion, hydrogel, microparticle, nanoparticle, microsphere, or solid surface.  
     
     
         3 . The composition of  claim 1 , wherein the carrier is a polymer.  
     
     
         4 . The composition of  claim 1 , wherein the carrier is a polymer having a molecular mass ranging from about 100 to about 100,000,000 daltons.  
     
     
         5 . The composition of  claim 1 , wherein the carrier is a polymer having a molecular mass ranging from about 10,000 to about 250,000 daltons.  
     
     
         6 . The composition of  claim 1 , wherein the carrier comprises a poly amino acid.  
     
     
         7 . The composition of  claim 1 , wherein the carrier comprises poly-lysine.  
     
     
         8 . The composition of  claim 1 , wherein the carrier comprises poly(ethyleneglycol).  
     
     
         9 . The composition of  claim 1 , wherein the carrier comprises a protective sidechain.  
     
     
         10 . The composition of  claim 9 , wherein the protective side chain comprises poly(ethylene glycol).  
     
     
         11 . The composition of  claim 9 , wherein the protective side chain comprises alkoxy poly(ethyleneglycol).  
     
     
         12 . The composition of  claim 9 , wherein the protective side chain comprises methoxy poly(ethyleneglycol) (MPEG).  
     
     
         13 . The composition of  claim 1 , wherein the metal binding domain comprises a nitrogen containing poly carboxylic acid.  
     
     
         14 . The composition of  claim 1 , wherein the metal binding domain comprises one or more of the following: 
 N-(hydroxy-ethyl)ethylenediaminetriacetic acid;    nitrilotriacetic acid (NTA);    ethylene-bis(oxyethylene-nitrilo)tetraacetic acid;    1,4,7,10-tetraazacyclodo-decane-N,N′,N″,N′″-tetraacetic acid;    1,4,7,10-tetraaza-cyclododecane-N,N′,N″-triacetic acid;    1,4,7-tris(carboxymethyl)-10-(2′-hydroxypropyl)-1,4,7,10-tetraazocyclodecane;    1,4,7-triazacyclonane-N,N′,N″-triacetic acid;    1,4,8,11-tetraazacyclotetra-decane-N,N′,N″,N′″-tetraacetic acid;    diethylenetriamine-pentaacetic acid (DTPA);    ethylenedicysteine;    bis(aminoethanethiol)carboxylic acid;    triethylenetetraamine-hexaacetic acid;    ethylenediamine-tetraacetic acid (EDTA);    1,2-diaminocyclohexane-N,N,N′,N′-tetraacetic acid; or    polypeptide.    
     
     
         15 . The composition of the  claim 14 , wherein the polypeptide has the formula: (AxHy)p where A is any amino acid residue, H is histidine, x is an integer from 0-6; y is an integer from 1-6; and p is an integer from 1-6.  
     
     
         16 . The composition of  claim 1 , wherein the metal ion is a transition metal ion.  
     
     
         17 . The composition of  claim 1 , wherein the metal ion is one or more of the following: Zn 2+ , Ni 2+ , Co 2+ , Fe 2+ , Mn 2+ , or Cu 2+ .  
     
     
         18 . The composition of  claim 1 , wherein the metal ion is Zn 2+  or Ni 2+ .  
     
     
         19 . The composition of  claim 9 , wherein the carrier comprises poly-L-lysine, the protective side chain comprises MPEG, the metal binding domain comprises NTA, and the metal ion is Ni 2+ .  
     
     
         20 . The composition of  claim 9 , wherein the carrier comprises poly-L-lysine, the protective side chain comprises MPEG, the metal binding domain comprises NTA, and the metal ion is Zn 2+ .  
     
     
         21 . A pharmaceutical composition comprising the composition of  claim 1 .  
     
     
         22 . The pharmaceutical composition of  claim 22 , wherein the pharmaceutical composition is an injectable composition.