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 glutathione-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 - 137 . (canceled)  
     
     
         138 . A composition, comprising: 
 an oxidized glutathione-based compound 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, the compound being stabilized with a metal material comprising a metal selected from the group consisting of platinum and palladium.    
     
     
         139 . The composition of  claim 138 , wherein the metal is platinum.  
     
     
         140 . The composition of  claim 139 , wherein the platinum material is selected from the group consisting of a platinum salt, a coordination compound, and an organometallic compound.  
     
     
         141 . The composition of  claim 140 , wherein the platinum material is a platinum coordination compound.  
     
     
         142 . The composition of  claim 141 , wherein the coordination compound is cis-platin.  
     
     
         143 . The composition of  claim 139 , wherein the platinum is present in an amount of between about 0.0003 molar equivalent to about 1 molar equivalent relative to the oxidized glutathione-based compound.  
     
     
         144 . The composition of  claim 143 , wherein the platinum is present in an amount of between about 0.001 molar equivalent to about 0.01 molar equivalent relative to the oxidized glutathione-based compound.  
     
     
         145 . The composition of  claim 138 , wherein the oxidized glutathione-based compound is a salt selected from the group consisting of alkali metal salts, alkaline earth metal salts, and transition metal salts.  
     
     
         146 . The composition of  claim 138 , wherein the oxidized glutathione-based compound is a salt selected from the group consisting of lithium salts, sodium salts, potassium salts, magnesium salts, calcium salts, vanadium salts, manganese salts, iron salts, molybdenum salts, and zinc salts.  
     
     
         147 . The composition of  claim 138 , wherein the composite is present in a dosage form for composition use.  
     
     
         148 . The composition of  claim 147 , wherein the dosage is between about 0.10 mg/kg to about 1.0 mg/kg by body weight.  
     
     
         149 . The composition of  claim 148 , wherein the dosage is between about 1 mg/m 2  to about 100 mg/m 2  by body surface.  
     
     
         150 . The composition of  claim 148 , wherein the composite is capable of being introduced in injectable form in a concentration between about 1% to about 10% by weight/volume.  
     
     
         151 . The composition of  claim 150 , wherein the composite is capable of being introduced in injectable form in a concentration between about 0.01% to about 3.0% by weight/volume.  
     
     
         152 . A method of stimulating endogenous production of cytokines and hemopoietic factors comprising introducing to a mammalian body in need of stimulation of cytokines or hemopoietic factors or both, an effective amount of a composition comprising an oxidized glutathione-based compound 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, the compound being stabilized with a metal material comprising a metal selected from the group consisting of platinum and palladium.  
     
     
         153 . The method of  claim 152 , wherein the metal is platinum.  
     
     
         154 . The method of  claim 153 , wherein the material is cis-platin.  
     
     
         155 . The method of  claim 152 , wherein the composition is administered orally.  
     
     
         156 . The method of  claim 152 , wherein the disease is selected from the group consisting of oncological, infectious, immunological, ischemic, neurodegenerative, metabolic, endocrinal, and other diseases.  
     
     
         157 . The method of  claim 152 , wherein the composition 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.