Iodothyronine polymers

• US 5,767,227 A
• Filed: 11/22/1994
• Issued: 06/16/1998
• Est. Priority Date: 11/03/1989
• Status: Expired due to Term

• Current Assignee: Shire LLC (Shire plc)
• Original Assignee: Lotus Biochemical Corporation
• Inventors: Latham, Vincent Ernest, Latham, Keith Roger
• Primary Examiner(s): Tsang, Cecilia J.
• Assistant Examiner(s): Lukton, David
• Application Number:
  US08/347,104
• Time in Patent Office: 1,302 Days
• Field of Search: 514/5, 514/12-17, 424/78.08, 530/324-328
• US Class Current: 530/324
• CPC Class Codes: C07D 263/44 Two oxygen atoms

Abstract

Iodothyronine polymers having a plurality of recurring units of formula I ##STR1## in which A is iodo and B, C and D are independently H or iodo are described. Polymers in which A and C are iodo and B and D are independently H or iodo and in which substantially all of the recurring units are L-stereoisomers, have utility in treating thyroid hormone deficiencies.

Claims

1. A substantially pure synthetic iodothyronine polymer having 5 to 400 recurring units, which may be the same or different, of the formula I ##STR7## in which A is iodo and B, C and D are independently H or iodo with a hydrogen atom at the N-terminus and a hydroxy group at the C-terminus and N=5-400.

2. An iodothyronine polymer as claimed in claim 1 in which substantially all of the recurring units of formula I are L-stereoisomers.

3. An iodothyronine polymer as claimed in claim 1 in which A and C are iodo and B and D are independently H or iodo.

4. An iodothyronine polymer as claimed in claim 3 in which at least one of B and D is iodo.

5. An iodothyronine polymer as claimed in claim 1 in which the number of recurring units in the polymer is in the range 10 to 400.

6. The iodothyronine polymer of claim 1 in which A and C are both iodo and in which B and D are both iodo in 70 to 90% of the monomers and only one of B and D is iodo in the remaining 10 to 30% of the monomers.

7. An iodothyronine polymer as claimed in claim 6 in which R is the side chain from one or more amino acids selected from the group consisting of lysine, arginine, aspartic acid, glutamic acid, serine or threonine.

8. A pharmaceutical composition suitable for treating thyroid hormone deficiencies comprising a pharmaceutically acceptable diluent or carrier and a pharmaceutically effective amount sufficient to raise blood levels of thyroid hormones the polymer of claim 1, in which polymer substantially all of the recurring units of formula I are L-stereoisomers with a hydrogen atom at the N-terminus and hydroxy group at the C-terminus.

9. The pharmaceutical composition of claim 8 in in which A and C are both iodo and in which B and D are both iodo in 70 to 90% of the monomers and only one of B and D is iodo in the remaining 10 to 30% of the monomers.

10. A pharmaceutical composition as claimed in claim 8, in which at least one of B or D is iodo.

11. A pharmaceutical composition as claimed in claim 8, in which the pharmacologically active ingredient comprises a mixture of pharmaceutically effective amounts of a first iodothyronine polymer in which B, C and D are iodo and a second iodothyronine polymer in which B and C are iodo and D is H.

12. A pharmaceutical composition as claimed in claim 11, in which the molar ratio of the amount of the first iodothyronine polymer to the amount of the second iodothyronine polymer lies in the range 7:

3 to 9;

1.

13. A pharmaceutical composition as claimed in claim 11, which also comprises a pharmaceutically effective amount sufficient to raise blood levels of thyroid hormones, of a further iodothyronine polymer in which B is H and C and D are iodo.

14. A pharmaceutical composition as claimed in claim 13, in which the ratio of the amount of the first iodothyronine polymer to the amount of the second iodothyronine polymer to the amount of the further iodothyronine polymer is apporoximately 80:

15;

5.

15. A method of treating thyroid hormone deficiencies comprising administering to a patient a therapeutically effective amount of the synthetic iodothyronine polymer of claim 8 sufficient to raise levels of thyroid hormones.

16. The method of claim 15 in which A and C are both iodo and in which B and D are both iodo in 70 to 90% of the monomers and only one of B and D is iodo in the remaining 10 to 30% of the monomers.

17. A method of treating thyroid hormone deficiencies as claimed in claim 15 in which at least one of B or D is iodo.

18. An N-carboxyanhydride compound of formula III ##STR8## in which A is iodo and B, C and D are independently H or iodo provided that at least one of B, C or D is H.

19. The N-carboxyanhydride compound of claim 18 in which said N-carboxyanhydride is an L-stereoisomer and in which A and C are iodo and at least one of B and D is iodo.

20. An N-carboxyanhydride compound as claimed in claim 19, in which A and C are iodo and at least one of B and D is iodo.