Dry-Powder Peptide Medicament

• US 20170087207A1
• Filed: 03/17/2015
• Published: 03/30/2017
• Est. Priority Date: 03/18/2014
• Status: Active Grant

• Current Assignee: Apeptico Forschung und Entwicklung GmbH
• Original Assignee: Apeptico Forschung und Entwicklung GmbH
• Inventors: Fischer, Bernhard
• Granted Patent: US 10,925,924 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 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/7012 Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid gluconic acid A61K31/191; ascorbic acid A61K31/375
• 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 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Disclosed is a dry-powder peptide medicament with a non-typical concentration of carbohydrate excipient, as well as said medicament for use in treatment or prevention of a disease or condition, as well as methods for manufacturing said medicament.

Claims

1. A dry-powder peptide medicament, wherein the medicament comprises

a peptide as active agent, wherein the peptide consists of 7-17 amino acids and includes the hexamer TX₁EX₂X₃E, wherein X₁, X₂ and X₃ can be any natural or non-natural amino acid, and wherein the peptide does not exhibit TNF-receptor-binding activity;

and

wherein the total carbohydrate concentration (w/w) in the medicament is less than 5%.

3. The medicament according to claim 1, wherein the medicament does not contain any excipient.

4. The medicament according to claim 1, wherein the total concentration (w/w) of sugars and sugar alcohols is less than 5%.

5. The medicament according to claim 1, wherein the peptide includes the amino-acid hexamer TPEGAE and/or the peptide is cyclic.

6. The medicament according to claim 1, wherein the peptide is cyclic and contains a sequence of consecutive amino acids selected from the group comprising

7. The medicament according to claim 1, wherein the peptide consists of the amino acid sequence CGQRETPEGAEAKPWYC and is cyclised via the C residues, preferably by a disulfide bond between the C residues.

8. The medicament according to claim 1, wherein the medicament consists of powder particles of a mean diameter of 0.5 to 10 micrometres.

9. The medicament according to claim 1, for use in treatment or prevention of a disease or condition, wherein the medicament is administered to a patient by inhalation.

10. The medicament according to claim 9, for use in treatment or prevention of a disease or condition selected from the group consisting of treatment of edema, preferably pulmonary edema;

and

vascular complications in diabetes patients such as micro- and macroangiopathy, myocardial infarction, microvascular cardiac hyperpermeability, stroke, neuropathy, retinopathy, nephropathy or diabetic foot disease; and

prevention of edema due to reduction in hyperpermeability, caused by injury of endothelial and/or epithelial layers, preferably edema occurring during treatment of pneumonia, acute lung injury, ARDS, bacterial or viral lung disease, more preferably edema occurring during infection by Listeria monocytogenes, Streptococcus pneumoniae, SARS virus, RSV or Influenza virus; and

the pulmonary form of altitude sickness.

11. The medicament according to claim 9, for use in treatment or prevention of influenza, wherein the medicament is administered together with an inhibitor of viral neuraminidase wherein the inhibitor is administered to said patient via a mode selected from the group consisting of oral, parenteral, intranasal, inhalation, rectal and topical administration.

12. The medicament according to claim 1, further comprising an inhibitor of viral neuraminidase for use in treatment or prevention of influenza, wherein the medicament is administered to a patient by inhalation.

16. The medicament according to claim 1, wherein the total carbohydrate concentration (w/w) in the medicament is less than 1%.

17. The medicament according to claim 1, wherein the total carbohydrate concentration (w/w) in the medicament is less than 0.1%.

18. The medicament according to claim 1, wherein the total carbohydrate concentration (w/w) in the medicament is less than 0.01%.

19. The medicament according to claim 8, wherein the medicament consists of powder particles of a mean diameter of 1 to 5 micrometres.

20. The medicament according to claim 8, wherein the medicament consists of powder particles of a mean diameter of 1 to 3.5 micrometres.

29. The medicament according to claim 1, substantially consisting of said peptide.

30. The medicament according to claim 29, wherein said peptide is a peptide with the sequence CGQRETPEGAEAKPWYC.

2. A dry-powder peptide medicament, wherein the medicament comprises

a peptide as single active agent, wherein the peptide consists of 7-17 amino acids and includes the hexamer TX₁EX₂X₃E, wherein X₁, X₂ and X₃ can be any natural or non-natural amino acid, and wherein the peptide does not exhibit TNF-receptor-binding activity;

and

wherein the total carbohydrate concentration (w/w) in the medicament is less than 5%

13. A method for manufacturing a dry-powder medicament comprising the steps of:

providing a peptide as an active agent, wherein the peptide consists of 7-17 amino acids and includes the hexamer TX₁EX₂X₃E, wherein X₁, X₂ and X₃ can be any natural or non-natural amino acid, and wherein the peptide does not exhibit TNF-receptor-binding activity;

dissolving or diluting the active agent in a liquid, yielding a solution wherein the carbohydrate content of total solids in solution is less than 5% (w/w); and

removing the solvent from said solution by spray drying, spray-freeze-drying, supercritical fluid precipitation, air-jet milling, lyophilisation or rotary evaporation to obtain the dry-powder medicament.

14. The method according to claim 13, wherein the sugar content and sugar alcohol content of total solids in solution is less than 5% (w/w).

15. The method according to claim 13, wherein

the total solids concentration before removal of the solvent is between 1-10% (w/v), and/or

the solvent is removed by spray drying and the inlet temperature of the spray dryer is between 50-110°

C., and the outlet temperature of the spray dryer is between 20-80°

C.

21. The method according to claim 13, wherein carbohydrate content of total solids in solution in the medicament is less than 1% (w/w).

22. The method according to claim 13, wherein carbohydrate content of total solids in solution in the medicament is less than 0.1% (w/w).

23. The method according to claim 13, wherein carbohydrate content of total solids in solution in the medicament is less than 0.01% (w/w).

24. The method according to claim 15, wherein the total solids concentration before removal of the solvent is between 2-4% (w/v).

25. The method according to claim 15, wherein the solvent is removed by spray drying and the inlet temperature of the spray dryer is between 70-90°

C.

26. The method according to claim 15, wherein the solvent is removed by spray drying and the inlet temperature of the spray dryer is between 75-85°

C.

27. The method according to claim 15, wherein the solvent is removed by spray drying and the outlet temperature of the spray dryer is between 40-60°

C.

28. The method according to claim 15, wherein the solvent is removed by spray drying and the outlet temperature of the spray dryer is between 45-55°

C.