Synthetic peptide amides
The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P 450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I: These compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.
1. A synthetic peptide amide having the formula:
D-Phe-D-Phe-D-Leu-D-Lys-[ω(4-aminopiperidine-4-carboxylic acid)]-OH or a pharmaceutically acceptable salt, hydrate, or acid salt hydrate thereof.
2. The synthetic peptide amide or pharmaceutically acceptable salt, hydrate, or acid salt hydrate thereof according to claim 1 , wherein the pharmaceutically acceptable salt or acid salt hydrate comprises HCl.
3. The synthetic peptide amide or pharmaceutically acceptable salt, hydrate, or acid salt hydrate thereof according to claim 1 , wherein the pharmaceutically acceptable salt or acid salt hydrate comprises acetic acid.
4. The synthetic peptide amide or pharmaceutically acceptable salt, hydrate, or acid salt hydrate thereof according to claim 1 , which is a solid composition.
5. The synthetic peptide amide or pharmaceutically acceptable salt, hydrate, or acid salt hydrate thereof according to claim 4 , herein the solid composition is a lyophilized solid composition.
6. A pharmaceutical composition comprising the synthetic peptide amide having the formula:
D-Phe-D-Phe-D-Leu-D-Lys-[ω(4-aminopiperidine-4-carboxylic acid)]-OH or a pharmaceutically acceptable salt, hydrate, or acid salt hydrate thereof and a pharmaceutically acceptable excipient or carrier.
7. The pharmaceutical composition according to claim 6 , wherein the pharmaceutical composition comprising the pharmaceutically acceptable excipient or carrier is an aqueous solution.
8. The pharmaceutical composition aqueous solution according to claim 7 , wherein the aqueous solution is an isotonic solution.
9. The pharmaceutical composition which is an aqueous solution according to claim 7 , wherein the aqueous solution is a buffered solution.
10. A method for the treatment of a kappa opioid receptor-associated disease or condition in a patient, wherein the kappa opioid receptor-associated disease or condition is pruritus, the method comprising administering to the patient a composition comprising an effective amount of a synthetic peptide amide having the formula:
D-Phe-D-Phe-D-Leu-D-Lys-[ω(4-aminopiperidine-4-carboxylic acid)]-OH or a pharmaceutically acceptable salt, hydrate, or acid salt hydrate thereof.
11. The method according to claim 10 , wherein the pruritus is associated with chronic kidney disease.
12. The method according to claim 11 , wherein the pruritus is associated with chronic kidney disease in a patient undergoing hemodialysis.
13. The method according to claim 11 , wherein the chronic kidney disease is end-stage renal disease.
14. The method according to claim 10 , wherein the pruritus is associated with a disease or condition selected from the group consisting of primary biliary cholangitis, primary biliary cirrhosis and chronic cholestatic liver disease.
15. The method according to claim 14 , wherein the pruritus is associated chronic cholestatic liver disease.
16. The method according to claim 10 , wherein the pruritus is associated with atopic dermatitis.
17. The method according to claim 10 , wherein the pruritus is associated with contact dermatitis.
18. The method according to claim 10 , wherein the pruritus is associated with psoriasis.