Sustained release thyroactive composition

• US 5,324,522 A
• Filed: 12/28/1992
• Issued: 06/28/1994
• Est. Priority Date: 12/30/1991
• Status: Expired due to Term

• Current Assignee: AKZO NV (Nouryon BV)
• Original Assignee: AKZO NV (Nouryon BV)
• Inventors: Hennemann, Georg, Krenning, Eric P.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): BENSTON JR, WILLIAM E
• Application Number:
  US07/997,474
• Time in Patent Office: 547 Days
• Field of Search: 562/447, 562/464, 562/424, 562/447, 424/426, 424/475, 424/482, 424/456, 514/567
• US Class Current: 424/456
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61P 5/12 for decreasing, blocking or antagonising the activity of the posterior pituitary hormones
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4

Abstract

Disclosed are sustained release dosage forms of liothyronine, in combination with normal or sustained release of thyroxine in a molar ratio of about 1 to 50:1, especially 5 to 20:1, useful in thyroid hormone replacement therapy. Surprisingly, it is found that by incorporating liothyronine and optionally thyroxine into a prolonged action dosage form in the described ratios, that the side effects associated with thyroid hormone replacement therapy are greatly reduced or eliminated. The preparation can be a dosage form containing salts of both thyroxine and liothyronine which release in a sustained manner. The preparations will typically contain 5 to 25 μg of liothryronine. Also disclosed are processes of manufacturing the pharmaceutical preparations. The compositions are useful in treating disease states such as hypothyroidism, hyperthyroidism (in combination with thyrostatic drugs), so-called "TSH" suppressive therapy, and depression.

Claims

1. A pharmaceutical composition for thyroid hormone replacement therapy comprising thyroxine and a controlled release form of 3,5,3'"'"'-triiodothyronine, said preparation containing from 1 to 50 parts of thyroxine to one part of 3,5,3'"'"'-triiodothyronine or pharmaceutically acceptable salts thereof.

2. The pharmaceutical composition of claim 1, which releases therefrom 5 to 25 μ

g of 3,5,3'"'"'-triiodothyronine.

3. The pharmaceutical composition of claim 2, wherein the thyroxine is levo-thyroxine in a form that releases in a controlled manner from said pharmaceutical composition.

4. The pharmaceutical composition of claim 2, wherein the 3,5,3'"'"'-triiodothyronine releases over a 1.5 to 24 hour period.

5. A pharmaceutical composition according to claim 1, comprising from 1 to 50 parts of thyroxine to one part of 3,5,3'"'"'-triiodothyronine, which releases thyroxine and 3,5,3'"'"'-triiodothyronine in a controlled release manner over a period of 1.5 to 24 hour.

6. A pharmaceutical composition according to claim 1, comprising salts of both levo-thyroxine and 3,5,3'"'"'-triidothyronine that are released in a molar ratio of about 1:

1 to 50;

1, respectively, and at least the 3,5,3'"'"'-triiodothyronine is in said preparation in a controlled release form.

7. A pharmaceutical dosage unit comprising levo-thyroxine and 3,5,3'"'"'-triiodothyronine, wherein the dosage unit releases from 25 to 200 μ

g of levothyroxine, and further releases, in a controlled manner, from 5 to 25 μ

g of 3,5,3'"'"'-triidothyronine, said levothyroxine and 3,5,3'"'"'-triidothyronine being released, in total, in a molar ratio of about 1;

1 to 50;

1.

8. A method of hormone replacement therapy comprising administering a pharmaceutical composition comprising 3,5,3'"'"'-triiodothyronine which releases, over a twelve hour period, 5 to 25 μ

g of 3,5,3'"'"'-triiodothyronine.