Compositions of stable T3 and methodes of use thereof

• US 20050059574A1
• Filed: 11/30/2001
• Published: 03/17/2005
• Est. Priority Date: 12/21/2000
• Status: Abandoned Application

• Current Assignee: Resuscitation Technologies LLC (Bristol-Myers Squibb Company), The Feinstein Institute for Medical Research (Northwell Health, Inc.)
• Original Assignee: The Feinstein Institute for Medical Research (Northwell Health, Inc.)
• Inventors: Ojamaa, Kaie, Rubin, Leo, Klein, Irwin
• Application Number:
  US09/998,346
• Publication Number:
  US 20050059574A1
• Time in Patent Office: Days
• US Class Current: 530/363
• 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 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 47/643 Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00

Abstract

This invention provides a stable composition containing T₃, serum albumin and water, wherein the T₃ has a half-life of at least five days, particularly at neutral pH. This invention further provides a method for emergency treatment of a patient with cardiac arrest and with cardiac electrical standstill to restore effective cardiac function, comprising administering to the patient a therapeutically effective amount of the stable composition.

Claims

1. A composition comprising T₃, serum albumin and water wherein the stability of T₃ is increased.

2. The composition according to claim 1, wherein the T₃ has a half-life of at least five days at a temperature range of about −

30°

C. to 70°

C.

3. The composition according to claim 1, wherein further comprising a pharmaceutically acceptable excipient.

4. The composition according to claim 3, suitable for use in intravenous administration.

5. The composition according to claim 3, suitable for use in direct cardiac administration.

6. The composition according to claim 3, suitable for use in parenteral administration.

7. The composition according to claim 3, suitable for use in mucosal administration.

8. The composition according to claim 7, wherein the mucosal administration is selected from the group consisting of intranasal, by-inhalation and buccal.

9. The composition according to claim 8, wherein the T₃ has a half-life of at least two weeks.

10. The composition according to claim 1, wherein the T₃ has a half-life of at least one month.

11. The composition according to claim 1, wherein the T₃ has a half-life of at least three months.

12. The composition according to claim 1, wherein the T₃ has a half-life of at least six months.

13. The composition according to claim 1, wherein the T₃ has a half-life of at least twelve months.

14. The composition according to claim 1, wherein the ratio of T₃ and the serum albumin is between about 0.001 and 0.1.

15. The composition according to claim 1, wherein the ratio of T₃ and the serum albumin is between 0.002 and 0.05.

16. The composition according to claim 3, wherein the serum albumin is human serum albumin.

17. The composition according to claim 3, wherein the serum albumin is bovine serum albumin.

18. The composition according to claim 1, wherein the T₃ has a concentration of between 0.02 mg/ml and 0.8 mg/ml.

19. The composition according to claim 1, wherein the T₃ has a concentration of between 0.01 mg/ml and 1.0 mg/ml.

20. The composition according to claim 1, wherein the T₃ has a concentration of between 0.1 mg/ml and 0.5 mg/ml.

21. The composition according to claim 1, wherein the T₃ has a concentration of about 0.1 mg/ml.

22. The composition according to claim 1, wherein the pH range is about 2.5 to 11.5.

23. The composition according to claim 1, wherein the pH range is about 4.0 to 10.

24. The composition according to claim 1, wherein the pH range is about 6.0 to 8.0.

25. The composition according to claim 1, wherein the pH range is about 6.5 to 7.5.

26. A method of treating of a patient with cardiac arrest, or with cardiac electrical standstill, to restore effective cardiac function, comprising administering to the patient a therapeutically effective amount of the composition according to claim 1.

27. The method according to claim 26, wherein the cardiac arrest is caused by electromechanical dissociation.

28. The method according to claim 26, wherein the cardiac electrical standstill is caused by a disease.

29. The method according to claim 26, wherein the composition is administered by direct injection to a heart cavity of the patient, or direct parenteral injection into a central venous line of the patient.

30. The method according to claim 26, wherein the composition is administered by parenteral injection or parenteral intravenous injection.

31. The method according to claim 26, wherein the composition is administered directly to the pulmonary system of the patient.

32. The method according to claim 26, wherein the composition is administered directly to the pulmonary system by direct endotracheal injection.

33. The method according to claim 26, wherein the composition is administered directly to the pulmonary system by infusion through a respiratory airway of the patient.

34. The method according to claim 26, wherein the composition is administered in at least one rapid bolus injection.

35. The method according to claim 26, wherein the composition is administered at between 0.1 and 20 μ

g T₃ per kg of body weight.

36. The method according to claim 26, wherein the composition is administered at between 0.2 and 10 μ

g T₃ per kg of body weight.

37. The method according to claim 26, wherein the composition is administered at between 0.3 and 5 μ

g T₃ per kg of body weight.

38. The method according to claim 26, wherein the composition is administered at 100 μ

g T₃ per kg of body weight.

39. The method according to claim 26, wherein the composition is administered via intravenous drip.

40. The method according to claim 26, wherein the composition is administered via mucosal delivery.