Role of N-2-Hydroxy-Ethyl-Piperazine-N'-2-Ethane Sulfonic Acid (HEPES) in Pain Control and Reversal of Demyelinization Injury

Abstract

Compositions and therapeutic uses of HEPES and derivatives in the treatment of pain associated with cancers and side-effects including post-chemotherapy cognitive impairment are disclosed herein. HEPES is also used to treat neurodegenerative and neurological diseases, demyelinization injuries, and side-effects and withdrawal symptoms associated with benzodiazepines, anti-depressants, and other neurological agents.

What is claimed is: 
     
         1 . A method of treating neurological impairment caused by one or more demyelination diseases, withdrawal symptoms, side-effects or both following treatment with anti-depressants, selective serotonin inhibitors (SSRI), or other neurological agents that cause demyelination in a subject in a human subject comprising the steps of:
 identifying a subject in need for treatment against the neurological impairment caused by one or more demyelination diseases, withdrawal symptoms, side-effects or both following treatment with anti-depressants, selective serotonin inhibitors (SSRI), or other neurological agents that cause demyelination; and   administering a pharmaceutical composition comprising N-2-hydroxy-ethyl-piperazine-N′-2-ethane sulfonic acid (HEPES) and derivatives thereof dissolved in sterile water, buffer, saline or other pharmaceutically acceptable carriers once daily at a dosage of 10-100 mg/kg of body weight, wherein the pharmaceutical composition is administered orally, subcutaneously, parenterally, intravenously, peritoneally, or intramuscularly.   
     
     
         2 . The method of  claim 1 , wherein the anti-depressants are selected from the group consisting of benzodiazepines, SSRIs, Serotonin-norepinephrine reuptake inhibitors (SNRIs), Noradrenergic and specific serotonergic antidepressants (NaSSAs), Norepinephrine (noradrenaline) reuptake inhibitors (NRIs), Norepinephrine-dopamine reuptake inhibitors (NDRIs), Selective serotonin reuptake enhancers (SSREs), Melatonergic agonists, Tricyclic antidepressants (TCAs), and Monoamine oxidase inhibitor (MAOIs), citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, zimelidine or any combinations thereof. 
     
     
         3 . The method of  claim 1 , wherein the HEPES is dissolved in sterile water for injection for oral, subcutaneous, parenteral, intravenous, peritoneal, or intramuscular administration. 
     
     
         4 . The method of  claim 1 , wherein the composition is administered once daily on a body weight basis at 10-100 mg/kg. 
     
     
         5 . The method of  claim 1 , wherein the composition treats the one or more demyelination diseases by restoring, repairing, and/or regenerating a myelin sheath. 
     
     
         6 . A pharmaceutical composition for treating neurological impairment caused by one or more demyelination diseases, withdrawal symptoms, side-effects following treatment with anti-depressants, selective serotonin inhibitors (SSRI), or other neurological agents that cause demyelination in a subject in a human subject comprising:
 N-2-hydroxy-ethyl-piperazine-N′-2-ethane sulfonic acid (HEPES) and derivatives thereof dissolved in sterile water, buffer, saline or other pharmaceutically acceptable carriers in an amount sufficient to treat the neurological impairment caused by one or more demyelination diseases, withdrawal symptoms, side-effects following treatment with anti-depressants, selective serotonin inhibitors (SSRI), or other neurological agents that cause demyelination; and   one or more excipients, diluents, extended or controlled release agents, coloring agents, preservatives or any combinations thereof.   
     
     
         7 . The composition of  claim 6 , wherein the one or more demyelination diseases comprise multiple sclerosis, transverse myelitis, Devic's disease, progressive multifocal leukoencephalopathy, optic neuritis, Leukodystrophies, Guillain-Barré syndrome, Charcot-Marie-Tooth Disease or any combinations thereof. 
     
     
         8 . The composition of  claim 6 , wherein the one or more demyelination diseases comprise Parkinson's disease, Alper's disease, Alzheimer's disease, Lou Gehrig's Disease Corticobasal degeneration, Creutzfeldt-Jakob disease, Frontotemporal lobar degeneration Huntington's disease, Krabbe's disease, Multiple System Atrophy, Multiple sclerosis, Pick's disease, Primary lateral sclerosis, Progressive Supranuclear Palsy, Refsum's disease, Sandhoff disease, Schilder's disease, Spinal muscular atrophy, Steele-Richardson-Olszewski disease or any combinations thereof. 
     
     
         9 . The composition of  claim 6 , wherein the composition treats the one or more demyelination diseases by restoring, repairing, and/or regenerating a myelin sheath. 
     
     
         10 . The composition of  claim 6 , wherein the pharmaceutical composition for treating symptoms associated with one or more demyelination disease in a subject comprising:
 N-2-hydroxy-ethyl-piperazine-N′-2-ethane sulfonic acid (HEPES) and derivatives thereof dissolved in sterile water, buffer, saline or other pharmaceutically acceptable carriers in an amount sufficient to treat the one or more demyelination diseases; and   one or more excipients, diluents, extended or controlled release agents, coloring agents, preservatives or any combinations thereof.   
     
     
         11 . The composition of  claim 6 , wherein the one or more demyelination diseases comprise cerebral palsy, Tourette's syndrome, choreia, athetosis, bipolar disorder, schizophrenia or any combinations thereof. 
     
     
         12 . A pharmaceutical composition for treating pain associated with a cancer, side-effects following cancer treatment including post-chemotherapy cognitive impairment caused by demyelination in a subject comprising:
 N-2-hydroxy-ethyl-piperazine-N′-2-ethane sulfonic acid (HEPES) and derivatives thereof dissolved in sterile water, buffer, saline or other pharmaceutically acceptable carriers in an amount sufficient to treat the pain associated with the cancer, side-effects following the cancer treatment including post-chemotherapy cognitive impairment or both caused by demyelination; and   one or more excipients, diluents, extended or controlled release agents, coloring agents, preservatives or any combinations thereof.   
     
     
         13 . The composition of  claim 12 , wherein the composition is used to treat pain associated with pancreatic cancer, breast cancer, colorectal cancer, ovarian cancer, lung cancer, cervical cancer, gastric cancer, liver cancer, melanomas, brain tumors, multiple myeloma, prostate cancer, or bladder cancer. 
     
     
         14 . The composition of  claim 12 , wherein the composition is used to treat post-chemotherapy cognitive impairment following a breast cancer treatment. 
     
     
         15 . The composition of  claim 12 , wherein the HEPES is dissolved in sterile water for injection for oral, subcutaneous, parenteral, intravenous, peritoneal, or intramuscular administration. 
     
     
         16 . The composition of  claim 12 , wherein the composition is administered once daily on a body weight basis at 10-100 mg/kg. 
     
     
         17 . A method of treating pain associated with a cancer, side-effects following cancer treatment including post-chemotherapy cognitive impairment or both caused by demyelination in a human subject comprising the steps of:
 identifying a subject in need for treatment against the pain associated with the cancer, side-effects following cancer treatment including post-chemotherapy cognitive impairment or both caused by demyelination; and   administering a pharmaceutical composition comprising N-2-hydroxy-ethyl-piperazine-N′-2-ethane sulfonic acid (HEPES) and derivatives thereof dissolved in sterile water, buffer, saline or other pharmaceutically acceptable carriers once daily at a dosage of 10-100 mg/kg of body weight, wherein the pharmaceutical composition is administered orally, subcutaneously, parenterally, intravenously, peritoneally, or intramuscularly.   
     
     
         18 . The method of  claim 17 , wherein the composition is used to pain associated with a pancreatic cancer, breast cancer, colorectal cancer, ovarian cancer, lung cancer, cervical cancer, gastric cancer, liver cancer, melanomas, brain tumors, multiple myeloma, prostate cancer, or bladder cancer. 
     
     
         19 . The method of  claim 17 , wherein the composition is used to treat post-chemotherapy cognitive impairment following a breast cancer treatment. 
     
     
         20 . The method of  claim 17 , wherein the HEPES is dissolved in sterile water for injection for oral, subcutaneous, parenteral, intravenous, peritoneal, or intramuscular administration.