| abstract |
A composition for use in the treatment of hyperlipidemia, gastroesophageal reflux related to obesity, steatohepatitis or hypercholesterolemia, comprising an insulinotropic peptide conjugate, which is: (i) exendin-4 linked to an Fc region of immunoglobulin through a linker non-peptidyl; or (ii) represented by the following formula 1: R1-X-R2-LF <Formula 1> wherein R1 is selected from the group consisting of deamino-histidyl, dimethyl-histidyl, beta-hydroxy imidazopropionyl, 4-imidazoacetyl and beta -imized propionic carboxy, R2 is selected from the group consisting of -NH2, -OH and -Lys, X is Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Y-Gln-Met-Glu -Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu- Z-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser or Gly -Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Y-Gln-Met- Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Z -Asn-Gly-Gly, Y is selected from the group consisting of Lys, Ser and Arg, Z is selected from the group consisting of Lys, Ser and Arg, L is a non-peptidyl linker and F is an immunoglobulin Fc, in wherein the non-peptidyl linker is selected from the group consisting of SMCC (4- (N-maleimido methyl) cyclohexane-1-carboxylate succinimidyl), SFB (4-formylbenzoate succinimidyl), polyethylene glycol, polypropylene glycol, polyvinyl pyrrolidone, copolymers of ethylene glycol and propylene glycol, polyoxyethoxylate polyols, polyvinyl alcohol, polysaccharides, dextran, polyvinyl ethyl ether, biodegradable polymers such as PLA (polylactic acid) and PLGA (polylactic-glycolic acid), chitonic acid polymers, lipid combinations thereof. |