Compositions for inhalation

Abstract

A pharmaceutical composition including a mixture of active compounds (A) a pharmaceutically active polypeptide, and (B) an enhancer compound which enhances the systemic absorption of the polypeptide in the lower respiratory tract of a patient, the mixture being in the form of a dry powder for inhalation in which at least 50% of the total mass of the active compounds consists of primary particles having a diameter less than or equal to about 10 microns, the primary particles optionally being formed into agglomerates.

What is claimed is:  
     
         1 . A pharmaceutical composition, comprising a mixture of active compounds (A) a pharmaceutically active polypeptide, and (B) an enhancer compound which enhances the systemic absorption of said polypeptide in the lower respiratory tract of a patient, said mixture being in the form of a dry powder for inhalation, in which at least 50% of the total mass of active compounds consists of primary particles having a diameter less than or equal to about 10 microns, said primary particles optionally being formed into agglomerates.  
     
     
         2 . A pharmaceutical composition as claimed in  claim 1 , additionally comprising a pharmaceutically acceptable carrier, which comprises either 
 (a) particles having a diameter of less than about 10 microns, such that at least 50% of the resultant powder consists of optionally agglomerated primary particles having a diameter of less than about 10 microns; or    (b) coarse particles, such that an ordered mixture is formed between the active compounds and the said carrier.    
     
     
         3 . The composition of  claim 1 , wherein said polypeptide is a polypeptide hormone.  
     
     
         4 . The composition of  claim 3 , wherein said hormone is vasopressin, a vasopressin analogue, desmopressin, glucagon, corticotropin (ACTH), gonadotrophin (luteinizing hormone, or LHRH), calcitonin, C-peptide of insulin, parathyroid hormone (PTH), human growth hormone (hGH), growth hormone (HG), growth hormone releasing hormone (GHRH), oxytocin, corticotropin releasing hormone (CRH), somatostatin analogs, gonadotropin agonist analogs (GnRHa), atrial natriuretic peptide (hANP), thyroxine releasing hormone (TRHrh), follicle stimulating hormone (FSH), or prolactin.  
     
     
         5 . The composition of  claim 1 , wherein said polypeptide is a growth factor, interleukin, polypeptide vaccine, enzyme, endorphin, glycoprotein, lipoprotein, or polypeptide involved in the blood coagulation cascade, that exerts its pharmacological effect systemically.  
     
     
         6 . The composition of  claim 1 , wherein said polypeptide has a molecular weight of less than 30 kD.  
     
     
         7 . The composition of  claim 1 , wherein said polypeptide has a molecular weight of less than 25 kD.  
     
     
         8 . The composition of  claim 1 , wherein said polypeptide has a molecular weight of less than 20 kD.  
     
     
         9 . The composition of  claim 1 , wherein said polypeptide has a molecular weight of less than 15 kD.  
     
     
         10 . The composition of  claim 1 , wherein said polypeptide has a molecular weight of less than 10 kD.  
     
     
         11 . The composition of  claim 1 , wherein said enhancer compound is a surfactant.  
     
     
         12 . The composition of  claim 11 , wherein said surfactant is a bile salt, a bile salt derivative, an alkyl gycoside, a cyclodextrin or derivative thereof, or a phospholipid.  
     
     
         13 . The composition of  claim 11 , wherein said surfactant is a salt of a fatty acid.  
     
     
         14 . The composition of  claim 11 , wherein said fatty acid has 10-14 carbon atoms.  
     
     
         15 . The composition of  claim 14 , wherein said fatty acid is capric acid.  
     
     
         16 . The composition of  claim 11 , wherein said surfactant is sodium caprate.  
     
     
         17 . An inhaler device containing the composition of  claim 1 .  
     
     
         18 . The inhaler device of  claim 17 , wherein said composition is in the form of said agglomerates, said device being configured to induce the majority of said agglomerates to break down into particles having a diameter less than or equal to about 10 microns, upon inhalation of said agglomerates from said device.  
     
     
         19 . The inhaler device of  claim 17 , which inhaler device is a unit dose, breath actuated, dry powder inhaler for single use.  
     
     
         20 . The inhaler device of  claim 17 , which inhaler device is a multi-dose, breath actuated, dry powder inhaler for multiple use.