US2016213695A1PendingUtilityA1

Phosphaplatins as neuroprotective agents

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Assignee: BOSE RATHINDRA NPriority: Feb 22, 2013Filed: Apr 5, 2016Published: Jul 28, 2016
Est. expiryFeb 22, 2033(~6.6 yrs left)· nominal 20-yr term from priority
Inventors:Rathindra N. BoseShadi MoghaddasHoma Dezvareh
A61P 3/10A61P 35/00A61P 43/00A61P 25/16A61P 25/02A61P 25/08A61P 25/14A61P 25/28A61P 27/02A61P 25/00A61P 17/02A61K 31/69A61K 45/06A61K 31/519A61K 31/675A61K 31/427A61N 5/10A61K 31/6615A61K 31/555A61K 31/255A61K 31/337A61K 33/243
37
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Claims

Abstract

The present disclosure provides for compositions for the treatment of neurodegenerative diseases comprising one or more isolated phosphate complexes of platinum and methods of uses thereof for treating neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease, stroke, epilepsy, Parkinsons, Huntington's disease and diabetes associated peripheral neuropathy The present disclosure is also directed towards an anti-angiogenic composition useful for inhibiting angiogenesis related to age-related macular degeneration, diabetic retinopathy and tumor-associated angiogenesis. An embodiment of the present disclosure is also directed towards a method for modulating the expression of Pigment Epithelial Derived Factor (PEDF) gene in an individual in need thereof. The present disclosure also provides for a method of reducing neurotoxicity associated with the administration of a cancer therapy in a subject in need thereof comprising administering to the individual in need thereof a therapeutically effective amount of at least one or more isolated monomeric phosphate complexes of platinum described herein.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of treatment of a neurodegenerative disease comprising:
 administering to a subject in need thereof a therapeutically effective amount of a composition comprising at least one isolated platinum complex selected from
 diammine(dihydrogen pyrophosphato)platinum(II), or 
 one or more isolated monomeric platinum complexes comprising a platinum center selected from Pt(II) and Pt(IV) and having a formula selected from I, II, III and IV: 
   
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  each is independently selected from substituted or unsubstituted aliphatic or aromatic amines, and wherein when one of R 1  and R 2  is NH 3 , the other of R 1  and R 2  is not NH 3 ; wherein each R 3  is selected from substituted or unsubstituted aliphatic or aromatic diamines; wherein S is independently selected from hydroxide, acetic acid, butyric acid, and alpha-hydroxy acids; or pharmaceutically acceptable salts thereof; and 
         at least one pharmaceutically acceptable carrier, diluent, adjuvant, or vehicle, wherein the composition is effective in modulating the Pigment Epithelial derived factor (PEDF) gene expression. 
       
     
     
         2 . The method of  claim 1 , wherein the neurodegenerative disease is selected from the group consisting of amyotrophic lateral sclerosis, Alzheimer's disease, stroke, epilepsy, Parkinsons, Huntington's disease, diabetes associated peripheral neuropathy, leg and foot ulcerations associated with diabetes and pain and sleep loss induced by diabetes associated neuropathy. 
     
     
         3 . The method of  claim 1 , administration is intravenously, orally, subcutaneously, intramuscularly, intraocularly or transdermally. 
     
     
         4 . The method of  claim 1 , wherein R 1  and R 2  are each independently selected from ammine, methyl amine, ethyl amine, propyl amine, isopropyl amine, butyl amine, cyclohexane amine, aniline, pyridine, and substituted pyridine. 
     
     
         5 . The method of  claim 1  wherein R 3  is selected from ethylenediamine and cyclohexanediamine. 
     
     
         6 . The method of  claim 1 , wherein the isolated monomeric platinum complex is 1,2-Ethanediamine(dihydrogen pyrophosphato)platinum(II). 
     
     
         7 . The method of  claim 1 , wherein the isolated monomeric platinum complex is (trans-1,2-cyclohexanediamine)(dihydrogen pyrophosphato)platinum(II). 
     
     
         8 . The method of  claim 1 , wherein the isolated monomeric platinum complex is cis-diammine-trans-dihydroxo(dihydrogen pyrophosphato)platinum(IV). 
     
     
         9 . The method of  claim 1 , wherein the isolated monomeric platinum complex is 1,2-Ethanediamine-trans-dihydroxo(dihydrogen pyrophosphato)platinum(IV). 
     
     
         10 . The method of  claim 1 , wherein the isolated monomeric platinum complex is trans-1,2-cyclohexanediamine)-trans-dihyroxo(dihydrogen pyrophosphato)platinum(IV). 
     
     
         11 . A method of reducing neurotoxicity associated with administration of a cancer therapy in a subject in need thereof comprising:
 administering to an individual in need thereof a therapeutically effective amount of a composition comprising at least one isolated monomeric platinum complex selected from
 diammine(dihydrogen pyrophosphato)platinum(II), or 
 one or more isolated monomeric platinum complexes comprising a platinum center selected from Pt(II) and Pt(IV) and having a formula selected from I, II, III and IV: 
   
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 2  each is independently selected from substituted or unsubstituted aliphatic or aromatic amines, and wherein when one of R 1  and R 2  is NH 3 , the other of R 1  and R 2  is not NH 3 ; wherein each R 3  is selected from substituted or unsubstituted aliphatic or aromatic diamines; wherein S is independently selected from hydroxide, acetic acid, butyric acid, and alpha-hydroxy acids; or pharmaceutically acceptable salts thereof; and
 at least one pharmaceutically acceptable carrier, diluent, adjuvant, or vehicle, and wherein the composition is effective in modulating the Pigment Epithelial derived factor (PEDF) gene expression. 
 
     
     
         12 . The method of  claim 11 , wherein the cancer therapy is a chemotherapeutic drug. 
     
     
         13 . The method of  claim 11 , wherein the chemotherapeutic drug is selected from paclitaxel, bortezomib, cyclophosphamide, eribulin mesylate, ixabepilone, cisplatin & oxaliplatin, methotrexate, and busulfan. 
     
     
         14 . The method of  claim 11 , wherein the cancer therapy is radiation therapy. 
     
     
         15 . The method of  claim 11 , wherein the cancer therapy is administered simultaneously. 
     
     
         16 . The method of  claim 11 , wherein R 1  and R 2  are each independently selected from ammine, methyl amine, ethyl amine, propyl amine, isopropyl amine, butyl amine, cyclohexane amine, aniline, pyridine, and substituted pyridine. 
     
     
         17 . The method of  claim 11 , wherein R 3  is selected from ethylenediamine and cyclohexanediamine. 
     
     
         18 . The method of  claim 11 , wherein the isolated monomeric platinum complex is 1,2-Ethanediamine(dihydrogen pyrophosphato)platinum(II). 
     
     
         19 . The method of  claim 11 , wherein the isolated monomeric platinum complex is (trans-1,2-cyclohexanediamine)(dihydrogen pyrophosphato)platinum(II). 
     
     
         20 . The method of  claim 11 , wherein the isolated monomeric platinum complex is cis-diammine-trans-dihydroxo(dihydrogen pyrophosphato)platinum(IV). 
     
     
         21 . The method of  claim 11 , wherein the isolated monomeric platinum complex is 1,2-Ethanediamine-trans-dihydroxo(dihydrogen pyrophosphato)platinum(IV). 
     
     
         22 . The method of  claim 11 , wherein the isolated monomeric platinum complex is trans-1,2-cyclohexanediamine)-trans-dihyroxo(dihydrogen pyrophosphato)platinum(IV).

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