Pharmaceutical compositions of melanocortin receptor ligands
View Patent ↗The present invention relates to improvements in compositions containing peptides that are ligands of one or more of the melanocortin receptors (MC-R), or pharmaceutically acceptable salts thereof, methods for preparing such compositions, and method of using such compositions to treat mammals. In particular, the present invention relates to a pharmaceutical composition comprising a pamoate salt of Ac-Arg-cyclo(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH 2 which is a ligand of the melanocortin receptor subtype 4 (MC4-R), and in which, after subcutaneous or intramuscular administration to a subject, the peptide forms a depot at physiological pH that is slowly dissolved and released into the body fluid and bloodstream. The present invention may further comprise an organic component such as dimethylacetamide (DMA) or polyethylene glycol (PEG) with an average molecular weight of lower than 1000.
1. A pharmaceutical composition for subcutaneous or intramuscular injection comprising a melanocortin receptor peptide ligand wherein
said peptide is a pamoate salt of Ac-Arg-cyclo(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;
said peptide is dissolved in a Polyethylene Glycol (PEG) 200 or PEG400 aqueous solution in which the volume-to-volume ratio of PEG to water is from about 1:9 to about 1:1 and the weight-to-volume concentration of said peptide is between about 200 mg/mL and about 300 mg/mL; and
said composition is a solution, a gel, a semi-solid or a suspension.
2. The pharmaceutical composition according to claim 1 , wherein the pH of said composition is between about 3.0 and about 8.0.
3. The pharmaceutical composition according to claim 2 , wherein said pamoate salt of Ac-Arg-cyclo(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH 2 is dissolved in a PEG400/aqueous solution, in which the volume-to-volume ratio of PEG400 to water is about 1:1 and the weight-to-volume concentration of the peptide is about 200 mg/mL.
4. The pharmaceutical composition according to claim 2 , wherein said pamoate salt of Ac-Arg-cyclo(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH 2 is dissolved in a PEG200/aqueous solution, in which the volume-to-volume ratio of PEG200 to water is about 1:1and the weight-to-volume concentration of the peptide is about 200 mg/mL.
5. The pharmaceutical composition according to claim 2 , wherein said pamoate salt of Ac-Arg-cyclo(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 is dissolved in a PEG400/Phosphate Buffered Saline (PBS) solution, in which the volume-to-volume ratio of PEG400 to PBS is about 1:1 and the weight-to-volume concentration of the peptide is about 300 mg/mL.
6. The pharmaceutical composition according to claim 2 , wherein said pamoate salt of Ac-Arg-cyclo(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH 2 is dissolved in a PEG400/saline solution, in which the volume-to-volume ratio of PEG400 to saline solution is about 1:1 and the weight-to-volume concentration of the peptide is about 300 mg/mL.
7. The pharmaceutical composition according to claim 1 , further comprising a preservative, m-cresol, phenol, benzyl alcohol, methyl paraben, an isotonic agent, a stabilizer, imidazole, arginine, histidine, a surfactant, a chelating agent, a buffer or a divalent metal ion, or any combination thereof.
8. The pharmaceutical composition according to claim 7 , wherein said preservative or isotonic agent is present in a concentration from about 0.01 mg/mL to about 100 mg/mL.
9. The pharmaceutical composition according claim 7 , wherein said buffer is selected from the group consisting of Tris, ammonium acetate, sodium acetate, glycine, aspartic acid, and Bis-Tris.
10. The pharmaceutical composition according to claim 7 , wherein said divalent metal is zinc.