Uses of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid

Abstract

The present invention relates to a method for maintaining a healthy bone structure by administering to a patient a bone health promoting effective amount of a medicament containing 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates.

What is claimed is:  
     
         1 . Use of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, for the manufacture of a medicament for selective modulation of osteoblasts.  
     
     
         2 . Use according to  claim 1  wherein the selective modulation comprises a stimulation of the cellular activities of the osteoblasts.  
     
     
         3 . Use according to  claim 1  or  claim 2  wherein the selective modulation comprises influencing the Ca 2+ -homeostasis of the osteoblasts.  
     
     
         4 . Use according to any of the foregoing claims wherein the selective modulation comprises a transient increase of the Ca 2+ -levels in the osteoblasts.  
     
     
         5 . Use of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, for the manufacture of a medicament for the maintenance of a healthy bone structure.  
     
     
         6 . Use according to  claim 5  wherein the medicament is applied in healthy patients.  
     
     
         7 . Use according to  claim 5  or  claim 6  wherein the medicament is applied in patients without osteopathies.  
     
     
         8 . Use according to any of  claims 5  to  7  wherein the medicament is applied in human beings or vertebrate animals.  
     
     
         9 . Use according to any of  claims 5  to  8  wherein the medicament is applied in human beings at or above the age of 40 years.  
     
     
         10 . Use according to any of  claims 5  to  8  wherein the medicament is applied in children.  
     
     
         11 . Use of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, for the manufacture of a medicament for the prevention of osteopathies in healthy patients.  
     
     
         12 . Use according to  claim 11  wherein the osteopathy is selected from the group comprising osteoporosis, Paget's disease, arthritis, periodontal osteopenia, adolescent scoliosis, fracture, disuse osteopenia, post-transplant osteopenia, hyper-parathyroidism-associated osteopenia, drug-induced osteopenia, nutritional osteopenia, metabolic bone disease, osteopenia of prematurity and ossification disorder.  
     
     
         13 . Use of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, for the manufacture of a medicament for the treatment of patients who have recently undergone treatment with corticosteroids.  
     
     
         14 . Use of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, for the manufacture of a medicament for post-treatment of osteopathies wherein an anti-resorptive activity is not desired.  
     
     
         15 . Use of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, for the manufacture of a medicament for the treatment of children having an osteopathy.  
     
     
         16 . Use according to  claim 15  wherein the osteopathy is selected from the group comprising osteoporosis, Paget's disease, arthritis, periodontal osteopenia, adolescent scoliosis, fracture, disuse osteopenia, post-transplant osteopenia, hyper-parathyroidism-associated osteopenia, drug-induced osteopenia, nutritional osteopenia, metabolic bone disease, osteopenia of prematurity and ossification disorder.  
     
     
         17 . Use according to any of the foregoing claims wherein 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, or any of its soluble salts or any of its hydrates, will—after the application of the medicament in a patient—be present at extracellular concentrations in a range between 10 −6 M and 10 −10 M.  
     
     
         18 . Use according to  claim 17  wherein 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, or any of its soluble salts or any of its hydrates, will—after the application of the medicament in a patient—be present at extracellular concentrations in a range between 10 −7 M and 10 −9 M.  
     
     
         19 . Use according to  claim 17  wherein 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, or any of its soluble salts or any of its hydrates, will—after the application of the medicament in a patient—be present at an extracellular concentration of about 10 −8 M.  
     
     
         20 . Use of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, for the manufacture of a medicament for the stimulation of those signaling cascades and reaction mechanisms mediating the action of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, which can be blocked by Ca 2+ -channel blockers.  
     
     
         21 . Use according to  claim 20  wherein the Ca 2+ -channel blockers are selected from the group comprising nifedipine and verapamil.  
     
     
         22 . Use according to any of the foregoing claims wherein 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, is used in doses of 0.01 to 1000 mg/oral application.  
     
     
         23 . Use according to  claim 22  wherein 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, is used in doses of 12.5 to 75 mg/oral application.  
     
     
         24 . Use according to any of the foregoing claims wherein 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, is used in doses of 0.02 to 200 mg/parenteral application.  
     
     
         25 . Use according to  claim 24  wherein 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, is used in doses of 2.5 to 15 mg/parenteral application.  
     
     
         26 . Use of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, for the manufacture of a medicament for the mobilization of Ca 2+ -ions from IP 3 -sensitive stores.  
     
     
         27 . Use of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, according to any of the foregoing claims wherein 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid or any of its soluble salts or any of its hydrates is combined with at least one substance selected from the group comprising calcium salts, calcium citrate, calcium carbonate, other amino-substituted bisphosphonates, pharmaceutically active fluorine-containing salts, vitamins of the D-Group and their metabolites, cholecalciferol, calcifediol, calcitriol, ergocalciferol, PTH, anabolic hormones, estrogens, substances with estrogenic activity on the bone, progestogens, androgens, growth hormones, peptides with growth hormone activity, selective modulators of the estrogenic receptor, raloxifene.  
     
     
         28 . Use of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, according to any of the foregoing claims, wherein the medicament is applied before, during or after treatment with other amino-substituted bisphosphonates.  
     
     
         29 . A method for screening for Ca 2+ -channel blockers comprising the steps: 
 treatment of cells having Ca 2+ -channels with a putative Ca 2+ -channel blocker;    contacting the cells with 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates;    measuring a response as a result of the contacting step.    
     
     
         30 . A method for screening for functional analogues of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid, any of its soluble salts or any of its hydrates, comprising the steps: 
 treatment of cells having Ca 2+ -channels with Ca 2+ -channel blockers;    contacting the cells with the putative functional analogue which, in the absence of any Ca 2+ -channel blockers, is known to cause a Ca 2+ -ion influx into the cells;    measuring a response as a result of the contacting step.    
     
     
         31 . A method for the selective modulation of osteoblasts and/or for the maintenance of a healthy bone structure and/or for the prevention of osteopathies in healthy patients and/or for the treatment of patients who have recently undergone treatment with corticosteroids, and/or for post-treatment of osteopathies where an anti-resorptive activity is not desired, and/or for the treatment of children having an osteopathy and/or for the stimulation of those signaling cascades and reaction mechanisms mediating the action of 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid or any of its soluble salts or any of its hydrates, which can be blocked by Ca 2+ -channel blockers, and/or for the mobilization of Ca 2+  ions from IP 3 -sensitive stores, comprising 
 administering 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid or any of its soluble salts or any of its hydrates alone or in combination with a pharmaceutical carrier to a patient, the 1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid or any of its soluble salts or any of its hydrates being administered in doses of 0.1 to 1000 mg/oral application or 0.02 to 200 mg/parenteral application.