Therapeutic preparation for inhalation

• US 5,658,878 A
• Filed: 06/06/1995
• Issued: 08/19/1997
• Est. Priority Date: 06/24/1993
• Status: Expired due to Term

• Current Assignee: Ab Astra
• Original Assignee: Ab Astra
• Inventors: Edman, Peter, Johansson, Ann Charlotte Birgit, Backstrom, Kjell Goran Erik, Dahlback, Carl Magnus Olof
• Primary Examiner(s): Woodward, Michael P.
• Assistant Examiner(s): PELLEGRINO, SUSAN
• Application Number:
  US08/471,488
• Time in Patent Office: 805 Days
• Field of Search: 514/3, 530/303
• US Class Current: 424/489
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin

Abstract

A therapeutic preparation for inhalation which comprises insulin and a substance which enhances the absorption of insulin in the lower respiratory tract, is provided in the form of a powder preparation suitable for inhalation.

Claims

1. A process for the manufacture of a therapeutic composition comprising insulin, comprising

forming, in a solvent, a solution of insulin and a substance which enhances the absorption of insulin in the lower respiratory tract;

removing the solvent to obtain a solid comprising said insulin and said substance; and

processing said solid to obtain a powder of which at least 50% of the total mass consists of particles which have a diameter of up to 10 microns.

2. A process as claimed in claim 1, comprising adding to said solution, in addition to said substance which enhances the absorption of insulin in the lower respiratory tract, a pharmaceutically acceptable carrier.

5. A process as claimed in claim 1, wherein the processing step comprises micronising the solid.

6. A process as claimed in claim 2, comprising the additional step of preparing an ordered mixture of said powder with a pharmaceutically acceptable carrier.

9. A process as claimed in claim 1, characterised in that the weight ratio of said insulin to said substance in said powder is in the range 9:

1 to 1;

1.

11. A process as claimed in claim 1, characterised in that the insulin is semisynthetic or biosynthetic human insulin.

13. A process as claimed in claim 1, characterised in that the substance is an anionic surfactant.

15. A process as claimed in claim 1, characterised in that said substance is a salt of a fatty acid.

17. A process as claimed in claim 15, characterised in that the fatty acid is capric acid.

19. A process as claimed in claim 1, characterised in that said substance is a bile salt.

21. A process as claimed in claim 19, characterised in that said bile salt is sodium taurocholate.

23. A process as claimed in claim 1, characterised in that said substance is a phospholipid, alkyl glycoside, cyclodextrin, or cyclodextrin derivative.

25. A process as claimed in claim 2, characterised in that said carrier is selected from a monosaccharide, a disaccharide, a polysaccharide, and a sugar alcohol.

27. A process as claimed in claim 2, characterized in that said carrier is selected from raffinose, melezitose, lactitol, maltitol, trehalose, sucrose, mannitol, and starch.

29. A process as claimed in claim 1, characterized in that said substance is a salt of ursodeoxycholate or glycocholate.

31. A process as claimed in claim 1, characterized in that said substance is a salt of taurocholate.

3. A process for the manufacture of a therapeutic composition comprising insulin, comprising dry-mixing insulin together with a substance which enhances the absorption of insulin in the lower respiratory tract, and processing said mixture to obtain a powder of which at least 50% consists of particles which have a diameter of up to 10 microns.

4. A process as claimed in claim 3, further comprising dry-mixing a pharmaceutically acceptable carrier together with the insulin and the substance which enhances the absorption of insulin in the lower respiratory tract.

7. A process as claimed in claim 3, wherein the processing step comprises micronising the mixture.

8. A process as claimed in claim 4, comprising the additional step of preparing an ordered mixture of said powder with a pharmaceutically acceptable carrier.

10. A process as claimed in claim 3, characterised in that the weight ratio of said insulin to said substance in said powder is in the range 9:

1 to 1;

1.

12. A process as claimed in claim 3, characterised in that the insulin is semisynthetic or biosynthetic human insulin.

14. A process as claimed in claim 3, characterised in that said substance is an anionic surfactant.

16. A process as claimed in claim 3, characterised in that said substance is a salt of a fatty acid.

18. A process as claimed in claim 16, characterised in that the fatty acid is capric acid.

20. A process as claimed in claim 3, characterised in that said substance is a bile salt.

22. A process as claimed in claim 20, characterised in that said bile salt is sodium taurocholate.

24. A process as claimed in claim 3, characterised in that said substance is a phospholipid, alkyl glycoside, cyclodextrin, or cyclodextrin derivative.

26. A process as claimed in claim 4, characterised in that said carrier is selected from a monosaccharide, a disaccharide, a polysaccharide, and a sugar alcohol.

28. A process as claimed in claim 4, characterized in that said carrier is selected from raffinose, melezitose, lactitol, maltitol, trehalose, sucrose, mannitol, and starch.

30. A process as claimed in claim 3, characterized in that said substance is a salt of ursodeoxycholate or glycocholate.

32. A process as claimed in claim 3, characterized in that said substance is a salt of taurocholate.