Active agent delivery systems and methods for protecting and administering active agents

• US 20040127397A1
• Filed: 12/05/2003
• Published: 07/01/2004
• Est. Priority Date: 08/22/2000
• Status: Abandoned Application

• Current Assignee: New River Pharmaceuticals Inc. (Shire plc)
• Original Assignee: New River Pharmaceuticals Inc. (Shire plc)
• Inventors: Kirk, Randall J., Piccariello, Thomas, Olon, Lawrence P.
• Application Number:
  US10/727,565
• Publication Number:
  US 20040127397A1
• Time in Patent Office: Days
• US Class Current: 514/2
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 47/55 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• CPC Class Codes: A61K 47/62 the modifying agent being a protein, peptide or polyamino acid
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65

Abstract

A composition comprising a polypeptide and an active agent covalently attached to the polypeptide. Also provided is a method for delivery of an active agent to a patient comprising administering to the patient a composition comprising a polypeptide and an active agent covalently attached to the polypeptide. Also provided is a method for protecting an active agent from degradation comprising covalently attaching the active agent to a polypeptide. Also provided is a method for controlling release of an active agent from a composition comprising covalently attaching the active agent to the polypeptide.

Claims

1. A method for controlling release of an active agent other than an amino acid in a patient comprising orally administering to said patient an amino acid/active agent complex comprising a polypeptide covalently attached to the active agent through an alcohol, an amine or a carboxylic acid functionality wherein said active agent enzymatically releases into the bloodstream following oral administration.

2. The method of claim 1, wherein the polypeptide includes of one or more of the twenty naturally occurring amino acids.

3. The method of claim 1, wherein said amino acid is glutamic acid, aspartic acid, arginine, asparagine, cysteine, lysine, threonine or serine.

4. The method of claim 1, wherein said amino acid is glutamic acid.

5. The method of claim 1, wherein said complex is in the form of an ingestible tablet, a capsule, or an oral suspension.

6. The method of claim 1, wherein said complex further comprises a microencapsulating agent.

7. The method of claim 1, wherein said complex further comprises an adjuvant covalently attached to said polypeptide.

8. A method for preparing a composition comprising a polypeptide and an active agent covalently attached to said polypeptide comprising the steps of:

(a) attaching the active agent to an amino acid to form an active agent/amino acid complex;

(b) forming an N-carboxyanhydride (NCA) from said active agent/amino acid complex; and

(c) polymerizing said N-carboxyanhydride (NCA).

9. The method of claim 8, wherein the active agent is attached to the side chain of said amino acid.

10. The method of claim 8, wherein the active agent is attached to the N-terminus of said amino acid.

11. The method of claim 8, wherein the active agent is attached to the C-terminus of said amino acid

12. The method of claim 8, further comprising the step of (d) granulating said complex.

13. The method of claim 8, wherein said amino acid is glutamic acid, aspartic acid, arginine, asparagine, cysteine, lysine, threonine or serine.

14. The method of claim 8, wherein said amino acid is glutamic acid.

15. The method of claim 8, wherein said amino acid is a synthetic amino acid with a pendant amine, alcohol, sulfhydryl, amide, urea, or acid functionality.