Novel compositions comprising a phosphodiesterase-5 inhibitor and their use in methods of treatment

Abstract

The invention relates generally to novel pharmaceutical methods for the treatment of various conditions. Compositions comprising: at least one phosphodiesterase-5-inhibitor in combination with one or more of the following medications: a selective serotonin reuptake inhibitor; a serotonin-norepinephrine reuptake inhibitor; a cholinesterase inhibitor; a dopamine agonist; or a medication suitable to increase the chemical concentrations of the neurotransmitters, selected from amino acids, monoamines, neuropeptides and other agents capable of primary neurotransmission in the synaptic clefts, and their use for treating a neurodegenerative disease in a subject. The invention also relates to: Compositions comprising: at least one phosphodiesterase-5-inhibitor in combination with one or more of the following medications: a selective serotonin reuptake inhibitor; or a cholinesterase inhibitor, and their use for treating damaged skin in a subject.

1 . A composition for treating a neurodegenerative disease in a subject comprising: at 
       least one phosphodiesterase-5 inhibitor in combination with one or more of the following medications:
 a selective serotonin reuptake inhibitor; 
 a serotonin-norepinephrine reuptake inhibitor; 
 a cholinesterase inhibitor; 
 a dopamine agonist; or 
 
       a medication suitable to increase the chemical concentrations of other neurotransmitters, selected from amino acids, monoamines, neuropeptides and other agents capable of primary neurotransmission in the synaptic clefts. 
     
     
         2 . The composition of  claim 1 , comprising at least one phosphodiesterase-5 inhibitor selected from the group consisting of tadalafil, vardenafil and sildenafil. 
     
     
         3 . The composition of  claim 1 , comprising at least one selective serotonin reuptake inhibitor selected from the group consisting of fluvoxamine, paroxetine, citalopram, sertraline and paroxetine. 
     
     
         4 . The composition of  claim 1 , comprising at least one serotonin-norepinephrine reuptake inhibitor selected from the group consisting of reboxatine venlafaxine and duloxetine. 
     
     
         5 . The composition of  claim 1 , comprising at least one cholinesterase inhibitor selected from the group consisting of tacrine and donepezil. 
     
     
         6 . The composition of  claim 1 , comprising at least one dopamine agonist selected from the group consisting of bromocryptine, carbidopa/levodopa and pramipexole. 
     
     
         7 . The composition of  claim 1 , wherein the medication suitable to increase the chemical concentrations of other neurotransmitters is selected from the group consisting of epinephrine, norepinephrine, dopamine, serotonin, melatonin, glutamic acid, gamma aminobutyric acid, aspartic acid, glycine, adenosine, ATP, GTP, vasopressin, somatostatin, neurotensin, leuteinizing hormone, insulin, histamine, nitrogen monoxide, carbon monoxide, acetylcholine. octopamine, tyramine, gastrin, cholecystokinin, oxytocin, neurophysin I, neurophysin II, neuropeptides Y, pancreatic polypeptide, peptide YY, corticotrophin, dynorphin, endorphin, enkephaline, secretin, motilin, glucagons, vasoactive intestinal peptide, growth hormone releasing factor, neurokinin A, neurokinin B, substance P, bombesin, gastrin releasing peptide, and anandamide. 
     
     
         8 . The composition of  claim 1 , wherein the medications are administered individually. 
     
     
         9 . The composition of  claim 1 , wherein the medications are in a combined from selected from the following:
 a once-weekly patch;   a monthly patch;   a long-term injection;   a combined pill; and   an implant.   
     
     
         10 . A method of treating neurodegenerative disease in a subject in need thereof comprising administering to the subject a pharmaceutically acceptable amount of a phosphodiesterase-5 inhibitor (PI-5) and one or more of the following medications:
 a selective serotonin reuptake inhibitor;   a serotonin-norepinephrine reuptake inhibitor;   a cholinesterase inhibitor;   a dopamine agonist; or   any suitable medication to increase the chemical concentrations of other neurotransmitters selected from amino acids, monoamines, neuropeptides and other agents capable of primary neurotransmission in the synaptic clefts.   
     
     
         11 . The method of  claim 10 , wherein the medications are formulated to be administered separately. 
     
     
         12 . The method of  claim 10 , wherein the medications are formulated to be administered in the same composition. 
     
     
         13 . The method of  claim 10 , wherein the neurodegenerative disease is Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, fronto-temporal dementia with Parkinson's features, progressive supranuclear palsies, essential dyskinesias, or dementia. 
     
     
         14 . The method of  claim 13 , wherein the disease is Alzheimer's disease. 
     
     
         15 . The method of  claim 13 , wherein the disease is Parkinson's disease. 
     
     
         16 . The method of  claim 13 , wherein the disease is multiple sclerosis. 
     
     
         17 . The method of  claim 13 , wherein the disease is amyotrophic lateral sclerosis. 
     
     
         18 . The method of  claim 13 , wherein the disease is fronto-temporal dementia with Parkinson's features. 
     
     
         19 . The method of  claim 13 , wherein the disease is progressive supranuclear palsies essential dyskinesias or dementia. 
     
     
         20 . The method of  claim 13 , wherein the disease is essential dyskinesias or dementia. 
     
     
         21 . The method of  claim 13 , wherein the disease is dementia. 
     
     
         22 - 59 . (canceled)