Inhalation administration of bisphosphonates

Abstract

The present invention relates to the treatment and prevention of bone diseases in humans, including osteoporosis in postmenopausal women, Paget's Disease and hypercalcemia, by administration of a bisphosphonate in an inhalation form. The invention also relates to pharmaceutical inhalation compositions suitable for the treatment and prevention of bone diseases.

What is claimed is:  
     
         1 . A method for treating or preventing bone reabsorption in a human in need thereof comprising administering to the respiratory tract of said human a therapeutically effective amount of a bisphosphonic acid, its pharmaceutically acceptable salts, or mixtures thereof.  
     
     
         2 . A method for the treatment and prevention of osteoporosis in postmenopausal women by administration to the respiratory tract of a therapeutically effective amount of a bisphosphonic acid, its pharmaceutically acceptable salts, or mixtures thereof.  
     
     
         3 . A method for treating or preventing bone reabsorption in a human in need thereof according to  claim 1  wherein the bisphosphonic acid is selected from the group consisting of alendronate, 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid; tiludronate, 4-chlorophenylthiomethylene bisphosphonatic acid; pamidronate, (3-amino-hydroxypropylidnen) bisphosphonic acid; etidronate, (1-hydroxy ethylidene) bisphosphonic acid; residronate, 1-hydroxy-2-(3-pyridinyl)ethylidene bisphosphonic acid; zoledronate, 2-(imidazol-1-yl)-1-hydroxyethane-1,1-bisphosphonic acid; and the pharmaceutically acceptable salts of the above compounds.  
     
     
         4 . A method for treating or preventing bone reabsorption in a human in need thereof according to  claim 1  wherein the bisphosphonic acid is alendronate, 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid, its pharmaceutically acceptable salts and mixtures thereof.  
     
     
         5 . A method for the treatment and prevention of osteoporosis in postmenopausal women according to  claim 2  wherein the bisphosphonic acid is selected from the group consisting of alendronate, 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid; tiludronate, 4-chlorophenylthiomethylene bisphosphonatic acid; pamidronate, (3-amino-hydroxypropylidnen) bisphosphonic acid; etidronate, (1-hydroxy ethylidene) bisphosphonic acid; residronate, 1-hydroxy-2-(3-pyridinyl)ethylidene bisphosphonic acid; zoledronate, 2-(imidazol-1-yl)-1-hydroxyethane-1,1-bisphosphonic acid; and the pharmaceutically acceptable salts of the above compounds.  
     
     
         6 . A method for the treatment and prevention of osteoporosis in postmenopausal women according to  claim 2  wherein the bisphosphonic acid is alendronate, 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid, its pharmaceutically acceptable salts and mixtures thereof.  
     
     
         7 . A pharmaceutical inhalation composition comprising bisphosphonic acid, its pharmaceutically acceptable salts, or mixtures thereof.  
     
     
         8 . A pharmaceutical inhalation composition according to  claim 7  comprising 50-100 micrograms of bisphosphonic acid for daily administration.  
     
     
         9 . A pharmaceutical inhalation composition according to  claim 7  comprising: 
 (a) bisphosphonic acid, its pharmaceutically acceptable salts, or mixtures thereof,  
 (b) propellant,  
 (c) optional lubricant, and  
 (d) optional surfactant.  
 
     
     
         10 . A pharmaceutical inhalation composition according to  claim 7  wherein the bisphosphonic acid is selected from the group consisting of alendronate, 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid; teludronate, 4-chlorophenyl thiomethylene bisphosphonatic acid; pamidronate, (3-amino-hydroxy propylidnen) bisphosphonic acid; etidronate, (1-hydroxyethylidene) bisphosphonic acid; residronate, 1-hydroxy-2-(3-pyridinyl)ethylidene bisphosphonic acid; zoledronate, 2-(imidazol-1-yl)-1-hydroxyethane-1,1-bisphosphonic acid; and the pharmaceutically acceptable salts of the above compounds.  
     
     
         11 . A pharmaceutical inhalation composition according to  claim 7  wherein the bisphosphonic acid is alendronate, 4-amino-1-hydroxy butylidene-1,1-bisphosphonic acid, its pharmaceutically acceptable salts, or mixtures thereof.  
     
     
         12 . A pharmaceutical inhalation composition according to  claim 7  wherein the bisphosphonic acid is coated with an enteric polymer.  
     
     
         13 . A pharmaceutical inhalation composition according to  claim 12  wherein the bisphosphonic acid is coated with an enteric polymer selected from the group consisting of sureteric, cellulose acetate phthalate, methacrylic acid copolymer, hydroxypropyl methylcellulose phthalate, aquacoat ECD 30, shellac and zein.  
     
     
         14 . A pharmaceutical inhalation composition according to  claim 12  wherein the bisphosphonic acid is selected from the group consisting of alendronate, 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid; teludronate, 4-chlorophenyl thiomethylene bisphosphonatic acid; pamidronate, (3-amino-hydroxy propylidnen) bisphosphonic acid; etidronate, (1-hydroxyethylidene) bisphosphonic acid; residronate, 1-hydroxy-2-(3-pyridinyl)ethylidene bisphosphonic acid; zoledronate, 2-(imidazol-1-yl)-1-hydroxyethane-1,1-bisphosphonic acid; and the pharmaceutically acceptable salts of the above compounds.  
     
     
         15 . A pharmaceutical inhalation composition according to  claim 12  wherein the bisphosphonic acid is alendronate, 4-amino-1-hydroxy butylidene-1,1-bisphosphonic acid, its pharmaceutically acceptable salts, or mixtures thereof.