VASOPRESSIN FORMULATIONS FOR USE IN TREATMENT OF HYPOTENSION

• US 20160220676A1
• Filed: 05/20/2015
• Published: 08/04/2016
• Est. Priority Date: 01/30/2015
• Status: Active Grant

• Current Assignee: Par Pharmaceutical, Inc. (Endo International PLC)
• Original Assignee: Par Pharmaceutical, Inc. (Endo International PLC)
• Inventors: Kenney, Matthew, Kannan, Vinayagam
• Granted Patent: US 9,744,239 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 38/095 Oxytocins; Vasopressins; Related peptides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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

Provided herein are peptide formulations comprising polymers as stabilizing agents. The peptide formulations can be more stable for prolonged periods of time at temperatures higher than room temperature when formulated with the polymers. The polymers used in the present invention can decrease the degradation of the constituent peptides of the peptide formulations.

Claims

1-15. -15. (canceled)

16. A method of increasing blood pressure in a human in need thereof, the method comprising:

a) providing a pharmaceutical composition for intravenous administration comprising, in a unit dosage form;

i) from about 0.01 mg/mL to about 0.07 mg/mL of vasopressin or a pharmaceutically-acceptable salt thereof;

chlorobutanol;

acetic acid; and

iv) water, wherein the unit dosage form has a pH of 3.4 to 3.6;

b) storing the unit dosage form at 2-8°

C.; and

c) administering the unit dosage form to the human;

wherein;

the administration provides to the human from about 0.01 units of vasopressin or the pharmaceutically-acceptable salt thereof per minute to about 0.1 units of vasopressin or the pharmaceutically-acceptable salt thereof per minute; and

the human is hypotensive

wherein the unit dosage form exhibits less than about 5% degradation after storage at 2-8°

C. for about four weeks.

17. The method of claim 16, wherein the unit dosage form further comprises SEQ ID NO.:

2 in an amount of about 0.01% after storage for about 4 weeks at 2-8°

C.

18. The method of claim 16, wherein the unit dosage form further comprises SEQ ID NO.:

3 in an amount of about 0.01% after storage for about 4 weeks at 2-8°

C.

19. The method of claim 16, wherein the unit dosage form further comprises SEQ ID NO.:

4 in an amount of about 0.01% after storage for about 4 weeks at 2-8°

C.

20. The method of claim 16, wherein the human'"'"'s mean arterial blood pressure is increased within 15 minutes of administration.

21. The method of claim 16, wherein the human'"'"'s hypotension is associated with vasodilatory shock.

22. The method of claim 21, wherein the vasodilatory shock is post-cardiotomy shock.

23. The method of claim 22, wherein the administration provides to the human from about 0.03 units of vasopressin or the pharmaceutically-acceptable salt thereof per minute to about 0.1 units of vasopressin or the pharmaceutically-acceptable salt thereof per minute

24. The method of claim 21, wherein the vasodilatory shock is septic shock.

25. The method of claim 24, wherein the administration provides to the human from about 0.01 units of vasopressin or the pharmaceutically-acceptable salt thereof per minute to about 0.07 units of vasopressin or the pharmaceutically-acceptable salt thereof per minute

26. The method of claim 16, the method further comprising attaining a target blood pressure in the human and continuing the administration for a period of about 8 hours.

27. The method of claim 26, the method further comprising, after the period of about 8 hours, reducing the administration by about 0.005 units per minute.

28. The method of claim 16, the method further comprising reaching a target increase in blood pressure of the human, wherein if the target increase in blood pressure is not attained, the administration is increased by about 0.005 units per minute at 10-15 minute intervals until the target increase in blood pressure is attained.

33. A method of increasing blood pressure in a human in need thereof, the method comprising:

a) providing a pharmaceutical composition for intravenous administration comprising, in a unit dosage form;

i) from about 0.01 mg/mL to about 0.07 mg/mL of vasopressin or a pharmaceutically-acceptable salt thereof;

chlorobutanol;

acetic acid; and

iv) water, wherein the unit dosage form has a pH of 3.4 to 3.6;

b) storing the unit dosage form at 2-8°

C. for 24 hours; and

c) thereafter administering the unit dosage form to the human;

wherein;

the administration provides to the human from about 0.01 units of vasopressin or the pharmaceutically-acceptable salt thereof per minute to about 0.1 units of vasopressin or the pharmaceutically-acceptable salt thereof per minute; and

the human is hypotensive.