Curcumin-peptide conjugates and formulations

Abstract

Disclosed here are compositions comprising a curcuminoid-peptide complex. Also disclosed are therapeutic compositions comprising a curcuminoid-peptide complex as described and a pharmaceutically acceptable excipient, diluent, or carrier.

What is claimed is: 
     
         1 . A curcuminoid composition comprising
 a curcuminoid bound to peptide to form a curcuminoid-peptide complex, wherein the peptide comprises at least 2 amino acids.   
     
     
         2 . The composition of  claim 1 , wherein the ratio of curcumin to peptide is between 1-50:1-50 w/w (mg:g). 
     
     
         3 . The composition of  claim 2 , wherein the w/w (mg:g) ratio of curcumin to peptide is about 1:1; 1:≦10; 10:≧1; 25:1; 1:25, 50:1 or 1:50. 
     
     
         4 . The composition of  claim 1 , wherein the curcuminoid is bound to the peptide through a linker. 
     
     
         5 . The composition of  claim 1 , wherein the linker is an alkyl, alkenyl, or alkynyl moiety. 
     
     
         6 . The composition of  claim 1 , wherein the linker is a substituted alkyl, a substituted alkenyl, or a substituted alkynyl moiety, wherein the substitution is a —OH, —SH, —COOH, —N—C(O)H, —N—C(O)OH, or —C(O)NH. 
     
     
         7 . The composition of  claim 1 , wherein the curcuminoid is selected from the group consisting of curcumin, desmethoxycurcumin, bisdesmethoxycurcumin, tetrahydrocurcumin, tetrahydrodesmethoxycurcumin, and tetrahydrobisdesmethoxycurcumin. 
     
     
         8 . The composition of  claim 1 , wherein the peptide is selected from the group consisting of a dipeptide, a tripeptide, an oligopeptide, a polypeptide, a protein, and a protein fragment. 
     
     
         9 . The composition of  claim 1 , wherein the peptide is selected from the group consisting of whey protein, tumor necrosis factor (TNF-α); cyclooxygenase (COX, COX-1 or COX-2); α1-acid glycoprotein; myeloid differentiation protein 2; a histone acetyl-transferases (HATs, or p300/CBP); histone deacetylases; glyoxalase I (GLOI); xanthine oxidase; a proteasome; sarco (endo) plasmic reticulum Ca 2+  ATPase; human immunodeficiency virus type 1 protease; DNA methyltransferases (DNMTs, DNMT1); DNA polymerase λ; a ribonucleases; a lipoxygenases; a matrix metalloproteinases; lysozyme; protein kinase C; cellular sarcoma; glycogen synthase kinase-3; ErbB2; phosphorylase kinase; thioredoxin reductase; aldose reductase; thioredoxin reductase; caseins; human serum albumin; bovine serum albumin; fibrinogen; β-lactoglobulin (β-LG); α-lactalbumin; human serum immunoglobulin; FtsZ; transthyretin; glutathione (GSH); and Kelch-like ECH-associated protein 1. 
     
     
         10 . The composition of  claim 1 , wherein the peptide is whey protein, rice protein, or pea protein. 
     
     
         11 . The composition of  claim 1 , wherein the curcuminoid and the peptide are conjugated by a covalent bond, an ionic interaction, a lipophilic (van der Waals) interaction, or a hydrogen bond. 
     
     
         12 . The composition of  claim 1 , wherein the curcuminoid and the peptide are conjugated by a covalent bond, an ionic interaction, a lipophilic 
     
     
         13 . The composition of  claim 1 , wherein the curcuminoid-peptide complex provides a serum C max  of curcumin of <500 ng/mL. 
     
     
         14 . The composition of  claim 13 , wherein the curcuminoid-peptide complex provides a serum C max  of curcumin of <100 ng/mL. 
     
     
         15 . The composition of  claim 1 , wherein the curcuminoid-peptide complex provides a serum C max  of curcumin of <<0.001% of the curcuminoid-peptide complex administered. 
     
     
         16 . A therapeutic curcuminoid composition comprising
 a curcuminoid bound to peptide to form a curcuminoid-peptide complex in a pharmaceutically acceptable excipient, diluent, or carrier, wherein the peptide comprises at least 2 amino acids and the curcuminoid-peptide complex provides a serum C max  of curcumin of <500 ng/mL.   
     
     
         17 . The therapeutic curcuminoid composition of  claim 16 , wherein the curcuminoid is bound to the peptide through a linker. 
     
     
         18 . The therapeutic curcuminoid composition of  claim 17 , wherein the linker is an alkyl, alkenyl, or alkynyl moiety. 
     
     
         19 . The therapeutic curcuminoid composition of  claim 16 , wherein the peptide is selected from the group consisting of a dipeptide, a tripeptide, an oligopeptide, a polypeptide, a protein, and a protein fragment. 
     
     
         20 . The therapeutic curcuminoid composition of  claim 16 , wherein the peptide is selected from the group consisting of whey protein, tumor necrosis factor (TNF-α); cyclooxygenase (COX, COX-1 or COX-2); α1-acid glycoprotein; myeloid differentiation protein 2; a histone acetyl-transferases (HATs, or p300/CBP); histone deacetylases; glyoxalase I (GLOI); xanthine oxidase; a proteasome; sarco (endo) plasmic reticulum Ca 2+  ATPase; human immunodeficiency virus type 1 protease; DNA methyltransferases (DNMTs, DNMT1); DNA polymerase A-; a ribonucleases; a lipoxygenases; a matrix metalloproteinases; lysozyme; protein kinase C; cellular sarcoma; glycogen synthase kinase-3; ErbB2; phosphorylase kinase; thioredoxin reductase; aldose reductase (ALR2); thioredoxin reductase; caseins; human serum albumin; bovine serum albumin; fibrinogen; β-lactoglobulin (β-LG); α-lactalbumin; human serum immunoglobulin; FtsZ; transthyretin; glutathione (GSH); and Kelch-like ECH-associated protein 1.