Heat-stable dry powder pharmaceutical compositions and methods

• US 9,925,144 B2
• Filed: 07/18/2014
• Issued: 03/27/2018
• Est. Priority Date: 07/18/2013
• Status: Active Grant

• Current Assignee: Mannkind Corporation
• Original Assignee: Mannkind Corporation
• Inventors: Fabio, Karine, Guarneri, Joseph J., Curley, Kieran, Grant, Marshall L., Leone-Bay, Andrea
• Primary Examiner(s): GUDIBANDE, SATYANARAYAN R
• Application Number:
  US14/905,236
• Publication Number:
  US 20160158156A1
• Time in Patent Office: 1,348 Days
• Field of Search: None
• 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 31/198 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 31/4172 Imidazole-alkanecarboxylic acids, e.g. histidine
• CPC Class Codes: A61K 38/095 Oxytocins; Vasopressins; Related peptides
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/23 Calcitonins
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/10 of the posterior pituitary hormones, e.g. oxytocin, ADH
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents

Abstract

Disclosed herein are heat-stable dry powders which include peptides or protein such as oxytocin for use as a pharmaceutical composition. The composition is highly stable at increased temperatures and relatively high humid environments, and are intended for storage at room temperature with an improved shelf-life. In particular, the dry powders are intended for inhalation, however, other routes of administration can be used when reconstituted in solution.

Claims

1. An inhalable spray-dried powder pharmaceutical formulation comprising an oxytocin synthetic peptide, a derivative or analog of said peptide;

zinc citrate or zinc chloride, and/or a pharmaceutically acceptable carrier or excipient, wherein the formulation is stable for at least 40 weeks at 40°

C. and 75% relative humidity.

2. The inhalable spray-dried powder pharmaceutical formulation of claim 1, wherein the formulation comprises zinc chloride.

3. The inhalable spray-dried powder pharmaceutical formulation of claim 1, wherein the pharmaceutically acceptable carrier or excipient is a sugar selected from mannose, mannitol, trehalose, or sorbitol.

4. The inhalable spray-dried powder pharmaceutical formulation of claim 1, wherein the pharmaceutically acceptable carrier or excipient is polyvinylpyrrolidone, polyethylene glycol, or a diketopiperazine.

5. The inhalable spray-dried powder pharmaceutical formulation of claim 4, wherein the diketopiperazine is fumaryl diketopiperazine or succinyl diketopiperazine.

6. The inhalable spray-dried powder pharmaceutical formulation of claim 1, wherein the zinc citrate or zinc chloride is in an amount ranging from 100 to 20 equivalents per mole of the oxytocin, the oxytocin analog or derivative thereof.

7. The inhalable spray-dried powder pharmaceutical formulation of claim 1, wherein said oxytocin synthetic peptide, a derivative, or an analog of said peptide is in an amount comprising up to 200 IU.

8. The inhalable spray-dried powder pharmaceutical formulation of claim 7, wherein said oxytocin synthetic peptide, a derivative, or an analog of said peptide is in an amount comprising up to 150 IU.

9. The inhalable spray-dried powder pharmaceutical formulation of claim 7, wherein said oxytocin synthetic peptide, a derivative, or an analog of said peptide is in an amount comprising up to 100 IU.

10. The inhalable spray-dried powder pharmaceutical formulation of claim 1, wherein said oxytocin synthetic peptide, a derivative, or an analog of said peptide is in an amount comprising up to 200 IU.

11. The inhalable spray-dried powder pharmaceutical formulation of claim 1, wherein said oxytocin synthetic peptide, a derivative, or an analog of said peptide is in an amount comprising up to 150 IU.

12. The inhalable spray-dried powder pharmaceutical formulation of claim 1, wherein said oxytocin synthetic peptide, a derivative, or an analog of said peptide is in an amount comprising up to 100 IU.

13. The inhalable spray-dried powder pharmaceutical formulation of claim 1, wherein said oxytocin synthetic peptide, a derivative, or an analog of said peptide is in an amount comprising up to 50 IU.

14. The inhalable spray-dried powder pharmaceutical formulation of claim 1, wherein the formulation comprises zinc citrate.

15. The inhalable spray-dried powder pharmaceutical formulation of claim 1, further comprising an amino acid selected from leucine, isoleucine, trileucine, cysteine, lysine, glycine, arginine, methionine, and histidine.

16. The inhalable spray-dried powder pharmaceutical formulation of claim 15, wherein the amino acid is leucine.

17. The inhalable spray-dried powder pharmaceutical formulation of claim 15, wherein the amino acid is isoleucine.

18. The inhalable spray-dried powder pharmaceutical formulation of claim 15, wherein the amino acid is trileucine.

19. The inhalable spray-dried powder pharmaceutical formulation of claim 15, wherein the amino acid is cysteine.

20. The inhalable spray-dried powder pharmaceutical formulation of claim 15, wherein the amino acid is lysine.

21. The inhalable spray-dried powder pharmaceutical formulation of claim 15, wherein the amino acid is glycine.

22. The inhalable spray-dried powder pharmaceutical formulation of claim 15, wherein the amino acid is arginine.

23. The inhalable spray-dried powder pharmaceutical formulation of claim 15, wherein the amino acid is methionine.

24. The inhalable spray-dried powder pharmaceutical formulation of claim 15, wherein the amino acid is histidine.