Iodothyronine compositions

• US 7,163,918 B2
• Filed: 05/02/2002
• Issued: 01/16/2007
• Est. Priority Date: 08/22/2000
• Status: Expired due to Term

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: New River Pharmaceuticals Inc. (Shire plc)
• Inventors: Piccariello, Thomas, Moncrief, James Scott, Olon, Lawrence Peter, Goldstein, Alex Saunders, Boerth, Nancy Johnston
• Primary Examiner(s): RUSSEL, JEFFREY E
• Application Number:
  US10/136,433
• Publication Number:
  US 20040087483A1
• Time in Patent Office: 1,720 Days
• Field of Search: 530/300, 530/345, 530/402, 530/409, 530/410, 514/5, 514/563, 514/567, 562/447
• US Class Current: 514/9.7
• CPC Class Codes: A61K 47/62 the modifying agent being a protein, peptide or polyamino acid
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT

Abstract

The present invention relates to compositions comprising thyroxine (T4) and triiodothyronine (T3). More specifically, the invention relates to thyroxine (T4) and triiodothyronine (T3) compositions that include a peptide carrier and thyroxine (T4) and triiodothyronine (T3) covalently attached to at least one of the N-terminus, the C-terminus, a side chain of the peptide carrier, and/or interspersed within the peptide chain; methods for protecting and administering thyroxine (T4) and triiodothyronine (T3); and methods for treating thyroid disorders.

Claims

1. A composition comprising:

a single T3 conjugated to the N-terminus of a peptide carrier,

wherein said peptide carrier is fewer than 15 amino acids and consists essentially of the one or more of the 20 naturally occurring amino acids; and

wherein said composition is in a form suitable for oral administration and delivery of a pharmaceutically effective amount of T3.

2. The composition of claim 1, comprising T3-Glu-Glu.

3. The composition of claim 1, comprising T3-Ser-Ser.

4. The composition of claim 1, comprising T3-PolySer.

5. The composition of claim 1, comprising T3-Lys.

6. The composition of claim 1, wherein said carrier peptide is an amino acid.

7. The composition of claim 1, wherein said composition formulations afford sustained release of T3.

8. The composition of claim 1, wherein said carrier peptide enhances absorption.

9. The composition of claim 1, wherein said carrier peptide is a homopolymer.

10. The composition of claim 1, wherein said carrier peptide is a heteropolymer.

11. The composition of claim 1, which is formulated to enhance the solubility of the T3 in aqueous or organic solvents.

12. The composition of claim 11, wherein said enhanced solubility allows even dispersion in polymer formulations.

13. A method of treating a thyroid hormone disorder comprising administering the composition of claim 1.

14. The composition of claim 1, wherein said form suitable for oral administration is a tablet, a capsule, a suspension, or a solution.

15. The composition of claim 1, wherein said carrier peptide consists of one or more of the 20 naturally occurring amino acids.

22. A method of treating a thyroid hormone disorder comprising administering the composition of claim 15.

16. A composition comprising a Glu-Glu carrier peptide that comprises at least one T3 active agent, with the proviso that no more than four T3 active agents are contiguously bonded.

23. A method of treating a thyroid hormone disorder comprising administering the composition of claim 16.

17. T3-Glu-Glu.

18. A composition comprising T3-Glu-Glu.

19. The composition of claim 18, wherein said T3-Glu-Glu is covalently attached to PEG.

20. The composition of claim 18, wherein said T3-Glu-Glu is covalently attached to cyclodextrin.

21. The composition of claim 18, wherein said T3-Glu-Glu is non-covalently attached to cyclodextrin.

25. A method of treating a thyroid hormone disorder comprising administering the composition of claim 18.

24. A method of treating a thyroid hormone disorder comprising administering T3-Glu-Glu.