Prodrugs of T3 and T4 with enhanced bioavailability
The invention relates to compositions of amino acid and peptide conjugates comprising T3 and/or T4. The T3 or T4 is covalently attached to at least one amino acid via the N-terminus, the C-terminus, a side chain of the peptide carrier, and/or interspersed within the peptide chain. Also discussed are methods for protecting and administering active agents and methods for treating thyroid disorders.
1 . A composition comprising at least one peptidic-iodothyronine or salt thereof and at least one non-peptidic iodothyronine or salt thereof.
2 . The composition of claim 1 comprising Gly-T3 or salt thereof and T4 or salt thereof.
3 . The composition of claim 1 comprising Gly-T4 or salt thereof and T3 or salt thereof.
4 . A composition comprising Gly-T3 or salt thereof and Gly-T4 or salt thereof.
5 . A method of treating a thyroid disorder comprising orally administering to a human patient an iodothyronine prodrug or salt thereof wherein said prodrug comprises a single iodothyronine covalently bound through to the C-terminus of peptide carrier wherein the carrier peptide is fewer than 5 amino acid.
6 . The method of claim 5 , wherein said iodothyronine is T3.
7 . The method of claim 5 , wherein said iodothyronine is T4.
8 . The method of claim 6 , wherein said carrier peptide is a single amino acid.
9 . The method of claim 6 , wherein said carrier peptide is Gly, Lys, Glu, Ile, Tyr, Val, Ala-Ala, Pro-Pro, Glu-Glu or Phe-Phe.
10 . The method of claim 8 , wherein said prodrug is in salt form.
11 . The method of claim 8 , wherein said salt form is a HCl, acetate, sulfate, mesylate, citrate, phosphate, or tartrate salt.
12 . The method of claim 8 , wherein said salt form is an HCl salt.
13 . The method of claim 8 , wherein said prodrug is Gly-T3 or a salt thereof.
14 . The method of claim 8 or 13 , wherein said condition is hypothyroidism.
15 . The method of claim 8 or 13 , wherein said condition is depression.
16 . Gly-T3.
17 . Ile-T3.
18 . Tyr-T3.
19 . Ala-Ala-T3.
20 . Val-T3.
21 . Pro-Pro-T3.
22 . Phe-Phe-T3.
23 . Gly-T4.
24 . Ile-T4.
25 . Tyr-T4.
26 . Ala-Ala-T4.
27 . Val-T4.
28 . Pro-Pro-T4.
29 . Phe-Phe-T4.
30 . T4-Glu.
31 . T4-Glu-Glu.
32 . T4-Lys.
33 . Glu-T4.
34 . Glu-Glu-T4.
35 . Lys-T4.