Methods for production of the oxidized glutathione composite with cis-diamminedichloroplatinum and pharmaceutical compositions based thereof regulating metabolism, proliferation, differentiation and apoptotic mechanisms for normal and transformed cells

Abstract

The present invention relates to a composite for the treatment of a variety of medical conditions, the composite comprising an oxidized gluthathione-based compound, which has a disulfide bond, and a metal material, in particular where the metal is either platinum or palladium. The oxidized glutathione-based compound and metal material can be present in a ratio of 3000 to 1 and preferably 1000 to 1. The oxidized glutathione-based compound can be oxidized glutathione itself or salts or derivatives. A feature of the invention is that the composite has a more stabilized disulfide bond than the oxidized glutathione-based compound itself. Methods for preparing the composite are provided, such methods being beneficial in that the composite is provided in high yields and at high purity. Methods for treating various medical conditions with the composites of the present invention are also disclosed.

1 . A method, comprising:
 introducing, to a subject in need of alteration of cellular redox potential, an effective amount of a composite comprising an oxidized glutathione-based compound and a metal material wherein the metal material comprises platinum or palladium, for a period of time sufficient alter a redox state of a cell within the immune system, thereby altering gene expression of immunologically significant genes within the subject.   
     
     
         2 . The method of  claim 1 , wherein the oxidized glutathione-based compound is formed from two monomers, each monomer comprising a glutamic acid bonded to a cysteine bonded to a glycine, the two monomers being linked through a disulfide bond bridging the sulfur atoms of each respective cysteine of each monomer. 
     
     
         3 . The method of  claim 1 , wherein the oxidized glutathione-based compound is selected from the group consisting of the formula: 
       
         
           
           
               
               
           
         
       
       and salts of said formula, wherein A, B, D, E, G and H can be the same or different and each is selected from the group consisting of an organic unit and salts of the organic unit. 
     
     
         4 . The method of  claim 1 , wherein the metal material is cis-platin. 
     
     
         5 . The method of  claim 1 , wherein the composite is administered orally. 
     
     
         6 . The method of  claim 1 , wherein the composite is administered as a solution form selected from the group consisting of inhalation solutions, local instillations, eye drops, intranasal introductions, ointment for epicutaneous applications, intravenous solutions, injection solutions, and suppositories. 
     
     
         7 . A method, comprising:
 introducing, to a subject in need of an increase in proliferation and/or differentiation of platelets, white blood cells, red blood cells, T lymphocytes, neutrophils, monocytes, macrophages, natural killer cells and/or B lymphocytes, an effective amount of a composite comprising an oxidized glutathione-based compound and a metal material wherein the metal material comprises platinum or palladium.   
     
     
         8 . The method of  claim 7 , wherein the oxidized glutathione-based compound is formed from two monomers, each monomer comprising a glutamic acid bonded to a cysteine bonded to a glycine, the two monomers being linked through a disulfide bond bridging the sulfur atoms of each respective cysteine of each monomer. 
     
     
         9 . The method of  claim 7 , wherein the oxidized glutathione-based compound is selected from the group consisting of the formula: 
       
         
           
           
               
               
           
         
       
       and salts of said formula, wherein A, B, D, E, G and H can be the same or different and each is selected from the group consisting of an organic unit and salts of the organic unit. 
     
     
         10 . The method of  claim 7 , wherein the metal material is cis-platin. 
     
     
         11 . The method of  claim 7 , wherein the composite is administered orally. 
     
     
         12 . The method of  claim 7 , wherein the composite is administered as a solution form selected from the group consisting of inhalation solutions, local instillations, eye drops, intranasal introductions, ointment for epicutaneous applications, intravenous solutions, injection solutions, and suppositories. 
     
     
         13 . A method, comprising:
 introducing, to a subject in need of alteration of a cellular protein, an effective amount of a composite comprising an oxidized glutathione-based compound and a metal material wherein the metal material comprises platinum or palladium.   
     
     
         14 . The method of  claim 13 , wherein the oxidized glutathione-based compound is formed from two monomers, each monomer comprising a glutamic acid bonded to a cysteine bonded to a glycine, the two monomers being linked through a disulfide bond bridging the sulfur atoms of each respective cysteine of each monomer. 
     
     
         15 . The method of  claim 13 , wherein the oxidized glutathione-based compound is selected from the group consisting of the formula: 
       
         
           
           
               
               
           
         
       
       and salts of said formula, wherein A, B, D, E, G and H can be the same or different and each is selected from the group consisting of an organic unit and salts of the organic unit. 
     
     
         16 . The method of  claim 13 , wherein the composite is introduced for a period of time sufficient to stimulate an increase in the phosphorylation of a cellular protein to obtain a therapeutic effect. 
     
     
         17 . The method of  claim 13 , wherein the composite is introduced for a period of time sufficient to stimulate an increase in the phosphorylation of tyrosine on a cytosolic protein to obtain a therapeutic effect. 
     
     
         18 . The method of  claim 13 , wherein the metal material is cis-platin. 
     
     
         19 . The method of  claim 13 , wherein the composite is administered orally. 
     
     
         20 . The method of  claim 13 , wherein the composite is administered as a solution form selected from the group consisting of inhalation solutions, local instillations, eye drops, intranasal introductions, ointment for epicutaneous applications, intravenous solutions, injection solutions, and suppositories. 
     
     
         21 - 34 . (canceled)