Claims for Patent: 6,004,574

Summary for Patent: 6,004,574

Title:	Powder formulations containing melezitose as a diluent
Abstract:	A powder formulation for the administration of medically useful polypeptides, comprising a medically useful polypeptide with melezitose as diluent.
Inventor(s):	Backstrom; Kjell (Lund, SE), Johansson; Ann (Lund, SE), Linden; Helena (Lund, SE)
Assignee:	Astra Aktiebolag (SE)
Application Number:	08/617,753
Patent Claims:	1. A powder formulation for the administration of a medically useful polypeptide by inhalation, consisting of a powder comprising a medically useful polypeptide with melezitose as diluent. 2. A powder formulation as claimed in claim 1, wherein the melezitose comprises D-melezitose (.alpha.-D-melezitose); 0-.alpha.-D-glucopyranosyl-1,3-.beta.-D-fructofuranosyl-.beta.-D-glucopyra noside (.beta.-D-melezitose); or isomelezitose. 3. A powder formulation as claimed in claim 1, wherein the melezitose is in the form of a monohydrate or dihydrate. 4. A powder formulation as claimed in claim 1, wherein the powder includes an enhancer which enhances the absorption of the medically useful polypeptide in the lower respiratory tract. 5. A powder formulation as claimed in claim 4, wherein the enhancer is selected from the group consisting of C.sub.8-16 fatty acids and salts thereof, bile salts, phospholipids and alkyl saccharides. 6. A powder formulation as claimed in claim 4, wherein the enhancer is selected from the sodium, potassium and lysine salts of caprylate (C.sub.8), caprate (C.sub.10), laurate (C.sub.12) and myristate (C.sub.14). 7. A powder formulation as claimed in claim 4, wherein the enhancer is a bile salt selected from the group consisting of salts of cholic acid, chenodeoxycholic acid, glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, deoxycholic acid, glycodeoxycholic acid, taurodeoxycholic acid, lithocholic acid, and ursodeoxycholic acid. 8. A powder formulation as claimed in claim 4, wherein the enhancer is a trihydroxy bile salt. 9. A powder formulation as claimed in claim 4, wherein the enhancer is selected from the group consisting of salts of cholic, glycocholic and taurocholic acids. 10. A powder formulation as claimed in claim 4, wherein the enhancer is selected from the group consisting of sodium and potassium salts of cholic, glycocholic and taurocholic acids. 11. A powder formulation as claimed in claim 4, wherein the enhancer is sodium taurocholate. 12. A powder formulation as claimed in claim 4, wherein the enhancer is a single-chain phospholipid. 13. A powder formulation as claimed in claim 4, wherein the enhancer is selected from the group consisting of lysophosphatidylcholines, lysophosphatidylglycerols, lysophosphatidylethanolamines, lysophosphatidylinositols and lysophosphatidylserines. 14. A powder formulation as claimed in claim 4, wherein the enhancer is a double-chain phospholipid. 15. A powder formulation as claimed in claim 4, wherein the enhancer is selected from the group consisting of diacylphosphatidylcholines, diacylphosphatidylglycerols, diacylphosphatidylethanolamines, diacylphosphatidylinositols and diacylphosphatidylserines. 16. A powder formulation as claimed in claim 4, wherein the enhancer is selected from the group consisting of dioctanoylphosphatidylglycerol, and dioctanoylphosphatidylcholine. 17. A powder formulation as claimed in claim 4, wherein the enhancer is selected from the group consisting of alkyl glucosides and alkyl maltosides. 18. A powder formulation as claimed in claim 1, wherein the polypeptide is selected from insulin, glucagon, C-peptide of insulin, vasopressin, desmopressin, corticotropin (ACTH), corticotropin releasing hormone (CRH), gonadotropin releasing hormone (GnRH), gonadotropin releasing hormone agonists and antagonists, gonadotrophin (luteinizing hormone, or LHRH), calcitonin, parathyroid hormone (PTH), bioactive fragments of PTH, growth hormone (GH), growth hormone releasing hormone (GHRH), somatostatin, oxytocin, atrial natriuretic factor (ANF), thyrotropin releasing hormone (TRH), deoxyribonuclease (DNase), prolactin, follicle stimulating hormone (FSH), and analogues thereof. 19. A powder formulation as claimed in claim 1, wherein the polypeptide is of molecular weight (MW) up to about 40 kD. 20. A powder formulation as claimed in claim 19, wherein the polypeptide has a molecular weight of up to 30 kD. 21. A powder formulation as claimed in claim 19, wherein the polypeptide has a molecular weight of up to 25 kD. 22. A powder formulation as claimed in claim 19, wherein the polypeptide has a molecular weight of up to 20 kD. 23. A powder formulation as claimed in claim 19, wherein the polypeptide has a molecular weight of up to 15 kD. 24. A powder formulation as claimed in claim 19, wherein the polypeptide has a molecular weight of up to 10 kD. 25. A powder formulation as claimed in claim 19, wherein the polypeptide has a molecular weight of up to 5 kD. 26. A powder formulation as claimed in claim 1, wherein the polypeptide is insulin. 27. A powder formulation as claimed in claim 1, wherein the melezitose is present in an amount of between 20% and almost 100% by weight of the powder. 28. A powder formulation as claimed in claim 27, wherein the melezitose is present in an amount of between 30% and almost 100% by weight of the powder. 29. A powder formulation as claimed in claim 28, wherein the melezitose is present in an amount of between 40% and almost 100% by weight of the powder. 30. A powder formulation as claimed in claim 29, wherein the melezitose is present in an amount of between 50% and almost 100% by weight of the powder. 31. A powder formulation as claimed in claim 30, wherein the melezitose is present in an amount of between 60% and almost 100% by weight of the powder. 32. A powder formulation as claimed in claim 31, wherein the melezitose is present in an amount of between 65% and almost 100% by weight of the powder. 33. A powder formulation as claimed in claim 32, wherein the melezitose is present in an amount of between 65% and 99% by weight of the powder. 34. A powder formulation as claimed in claim 33, wherein the melezitose is present in an amount of between 70% and 99% by weight of the powder. 35. A powder formulation as claimed in claim 34, wherein the melezitose is present in an amount of between 80% and 98% by weight of the powder. 36. A powder formulation as claimed in claim 1, wherein at least 50% of the polypeptide in the formulation consists of (a) primary particles having a diameter of between 0.01 and 10 microns, or (b) agglomerates of said particles. 37. A powder formulation as claimed in claim 1, wherein at least 50% of the polypeptide in the formulation consists of (a) primary particles having a diameter of between 1 and 6 microns, or (b) agglomerates of said particles. 38. A powder formulation as claimed in claim 36, wherein at least 60% of the polypeptide in the formulation consists of (a) primary particles having a diameter of between 0.01 and 10 microns, or (b) agglomerates of said particles. 39. A powder formulation as claimed in claim 38, wherein at least 70% of the polypeptide in the formulation consists of (a) primary particles having a diameter of between 0.01 and 10 microns, or (b) agglomerates of said particles. 40. A powder formulation as claimed in claim 39, wherein at least 80% of the polypeptide in the formulation consists of (a) primary particles having a diameter of between 0.01 and 10 microns, or (b) agglomerates of said particles. 41. A powder formulation as claimed in claim 40, wherein at least 90% of the polypeptide in the formulation consists of (a) primary particles having a diameter of between 0.01 and 10 microns, or (b) agglomerates of said particles. 42. A powder formulation as claimed in claim 1, wherein the melezitose consists essentially of particles having a diameter of less than about 10 microns. 43. A powder formulation as claimed in claim 1, wherein the melezitose consists essentially of particles of diameter over 20 microns. 44. A powder formulation as claimed in claim 43, wherein the melezitose consists essentially of particles having a diameter of 60-800 microns. 45. A powder formulation as claimed in claim 1, wherein no enhancer is included in the powder. 46. A method for the manufacture of a powder formulation as claimed in claim 1, comprising the steps of drying mixing the polypeptide and melezitose, and micronising the substances together. 47. A method for the manufacture of a powder formulation as claimed in claim 1, comprising the steps of micronising the polypeptide to produce a micronised polypeptide powder; separately micronising the melezitose to produce a micronised melezitose powder; and mixing the micronised powders. 48. A method for the manufacture of a powder formulation as claimed in claim 1, comprising the steps of dissolving the components in a solvent to produce a solution: and removing the solvent from the solution to produce a solid. 49. A method for the manufacture of a powder formulation as claimed in claim 43, comprising dry mixing the melezitose and a micronised polypeptide powder. 50. A method for the treatment of a patient in need of therapy, comprising administering to said patient a therapeutically effective amount of a powder formulation as claimed in claim 1. 51. The method of claim 50, wherein the medically useful polypeptide is insulin. 52. The method of claim 50, wherein the powder formulation is administered by providing it to the patient for inhalation. 53. The method of claim 50, wherein the powder formulation is administered from a dry powder inhaler device. 54. The method of claim 50, wherein the powder formulation is provided suspended in a propellant, and is administered from an aerosol inhaler device. 55. The method of claim 50, wherein the powder includes an enhancer which enhances the absorption of the medically useful polypeptide in the lower respiratory tract. 56. The method of claim 55, wherein the enhancer is selected from the group consisting of C.sub.8-16 fatty acids and salts thereof, bile salts, phospholipids and alkyl saccharides. 57. The method of claim 55, wherein the enhancer is selected from the sodium, potassium and lysine salts of caprylate (C.sub.8), caprate (C.sub.10), laurate (C.sub.12), and myristate (C.sub.14). 58. The method of claim 55, wherein the enhancer is a bile salt selected from the group consisting of salts of cholic acid, chenodeoxycholic acid, glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, deoxycholic acid, glycodeoxycholic acid, taurodeoxycholic acid, lithocholic acid, and ursodeoxycholic acid. 59. The method of claim 55, wherein the enhancer is selected from the group consisting of sodium and potassium salts of cholic, glycocholic and taurocholic acids. 60. The method of claim 55, wherein the enhancer is sodium taurocholate. 61. The method of claim 55, wherein the enhancer is a single-chain phospholipid. 62. The method of claim 55, wherein the enhancer is a double-chain phospholipid. 63. The method of claim 55, wherein the enhancer is selected from the group consisting of alkyl glucosides and alkyl maltosides. 64. The method of claim 50, wherein the polypeptide is selected from the group consisting of insulin, glucagon, C-peptide of insulin, vasopressin, desmopressin, corticotropin (ACTH), corticotropin releasing hormone (CRH), gonadotropin releasing hormone (GnRH), gonadotropin releasing hormone agonists and antagonists, gonadotrophin (luteinizing hormone, or LHRH), calcitonin, parathyroid hormone (PTH), bioactive fragments of PTH, growth hormone (GH), growth hormone releasing hormone (GHRH), somatostatin, oxytocin, atrial natriuretic factor (ANF), thyrotropin releasing hormone (TRH), deoxyribonuclease (DNase), prolactin, follicle stimulating hormone (FSH), and analogues thereof. 65. The method of claim 50, wherein the polypeptide is of molecular weight (MW) up to about 15 kD. 66. The method of claim 50, wherein the melezitose is present in an amount of between 20% and almost 100% by weight of the powder. 67. The method of claim 50, wherein at least 80% of the polypeptide in the formulation is in the form of (a) primary particles having a diameter of between 0.01 and 10 microns, or (b) agglomerates of said particles. 68. The method of claim 50, wherein the melezitose consists essentially of particles having a diameter of less than about 10 microns. 69. The method of claim 50, wherein the melezitose consists essentially of particles of diameter over 20 microns. 70. The powder formulation of claim 1, said powder formulation being suspended in a propellant suitable for aerosol delivery. 71. The method of claim 48, comprising the additional step of adjusting the pH of the solution prior to removing the solvent. 72. The method of claim 48, comprising the additional step of micronising the solid to produce a micronised powder.

Details for Patent 6,004,574

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2014-12-22