3,5,3'-TRIIODOTHYRONINE SULFATE AS THYROMIMETIC AGENT AND PHARMACEUTICAL FORMULATIONS THEREOF

• US 20110245342A1
• Filed: 04/08/2011
• Published: 10/06/2011
• Est. Priority Date: 11/13/2002
• Status: Abandoned Application

• Current Assignee: Bracco SPA
• Original Assignee: Bracco SPA
• Inventors: Santini, Ferruccio, Maisano, Federico, PINCHERA, Aldo, Vella, Fulvia, Cavalieri, Livio, Rivolta, Giovanni
• Application Number:
  US13/083,047
• Publication Number:
  US 20110245342A1
• Time in Patent Office: Days
• US Class Current: 514/562
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/28 Compounds containing heavy metals
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: G01N 21/76 Chemiluminescence; Bioluminescence
• CPC Class Codes: G01N 33/561 Immunoelectrophoresis
• CPC Class Codes: G01N 33/78 Thyroid gland hormones , e.g. T3, T4, TBH, TBG or their receptors

Abstract

The invention regards the use of triiodothyronine sulfate, commonly named T₃S, as a medicament having thyromimetic activity for the treatment of pathologies due to organic deficiency of triiodothyronine (T₃), as such or in association with thyroxine (T₄), and pharmaceutical formulations for oral administration thereof.

Claims

1. A solid oral dosage composition comprising T₃S as the active principle, in a quantity ranging from 1 to 1000 μ

g and further comprising diluents, glidants or lubricants and disintegrants.

2. The solid dosage of claim 1 wherein T₃S comprises 2.5 to 500 μ

g.

3. The solid dosage of claim 2 wherein T₃S comprises 5-250 μ

g.

4. The solid dosage of claim 2 further comprising 5-800 μ

g T₄ (thyroxine).

5. The solid dosage of claim 1 wherein said diluent is selected in the group consisting of:

cellulose and derivatives thereof, kaolin, starch and derivatives thereof and alkaline inorganic salts.

6. The solid dosage of claim 5 wherein the cellulose derivative is selected from the group consisting of:

microcrystalline cellulose or salts thereof, powdered cellulose, silicified microcrystalline cellulose, cellulose acetate or salts thereof, and ethyl cellulose or salts thereof.

7. The solid dosage of claim 5 wherein the alkaline inorganic salt is selected in the group consisting of:

tri-sodium phosphate, tri-calcium phosphate, calcium sulphate, and calcium or magnesium carbonate.

8. The solid dosage of claim 1 wherein the disintegrant is selected in the group consisting of:

corn starch, croscarmellose or salts thereof, crospovidone or salts thereof, polymethacrylates and maltodextrin or salts thereof.

9. The solid dosage of claim 8 wherein the disintegrant is croscarmellose or salts thereof.

10. The solid dosage of claim 1 wherein the lubricant is selected from the group consisting of:

silicates, including hydrate silicon dioxide, hydrate colloidal silica;

magnesium stearate;

zinc stearate; and

talc.

11. The solid dosage of claim 1 wherein the glidant is selected in the group consisting of:

glycerol dibehenate, tri-basic calcium phosphate, starch derivatives, talc, magnesium stearate and zinc stearate.

12. The solid dosage of claim 11 wherein the glidant is glycerol dibehenate or tribasic calcium phosphate.

13. The solid dosage of claim 1 in the form of a tablet.

14. The solid dosage composition of claim 1, comprising calcium carbonate, glycerol dibehenate, croscarmellose sodium salt, hydrate colloidal silica, magnesium stearate and microcrystalline cellulose.

15. The solid dosage form of any one of claims 1 or 4 which comprises:

22. A kit comprising a container for a solid oral dosage composition according to any one of claims 2 or 4 and, optionally, a container for a non-radioactive immunoassay for T₃S quantitation comprising a non radioactive T₃S-conjugate.

25. A therapeutic treatment method for a hypothyroid condition comprising administering a composition according to any one of claims 1, 4, 13 or 14.

26. The therapeutic treatment method of claim 25 wherein said hypothyroid condition is selected form the group consisting of:

asthenia, fatigue, skin dryness, somnolence, speech fluency impairment, cold intolerance, weight gain and memory deficit.

27. The solid dosage of claim 1 administered as a daily dose.

16. A non radioactive immunoassay for T₃S quantitation comprising a non radioactive T₃S-conjugate.

17. The immunoassay of claim 16 wherein the non radioactive conjugate is T₃S-biotin.

18. The immunoassay of claim 17 wherein the immunoassay is a competitive ELISA.

19. The immunoassay of claim 16 wherein the non radioactive conjugate is a T₃S conjugate comprising the compound of Formula I as a Lanthanide chelating agent

20. The immunoassay of claim 16 comprising a DELFIA®

assay.

21. A kit comprising a container for a non radioactive immunoassay according to claim 16 and a container for a solid oral dosage composition comprising T₃S as the active principle, in a quantity ranging from 1 to 1000 μ

g and further comprising diluents, glidants or lubricants and disintegrants.

23. A therapeutic or prophylactic treatment method for a hypothyroid condition due to total thyroid hormone depletion before ¹³¹I radiotherapy comprising administering a thyroidectomised patient T₃S as the sole thyroid hormone replacement up to 5 days before radioactive isotope administration.

24. The therapeutic treatment method of claim 23 wherein said hypothyroid condition is selected form the group consisting of:

asthenia, fatigue, skin dryness, somnolence, speech fluency impairment, cold intolerance, weight gain and memory to deficit.