Methods, Compositions and Articles of Manufacture for Enhancing Survivability of Cells, Tissues, Organs, and Organisms

Abstract

The present invention concerns the use of oxygen antagonists and other active compounds for inducing stasis or pre-stasis in cells, tissues, and/or organs in vivo or in an organism overall, in addition to enhancing their survivability. It includes compositions, methods, articles of manufacture and apparatuses for enhancing survivability and for achieving stasis or pre-stasis in any of these biological materials, so as to preserve and/or protect them. In specific embodiments, there are also therapeutic methods and apparatuses for organ transplantation, hyperthermia, wound healing, hemorrhagic shock, cardioplegia for bypass surgery, neurodegeneration, hypothermia, and cancer using the active compounds described.

1 .- 66 . (canceled) 
     
     
         67 . A method for enhancing survivability of biological matter comprising administering to the matter an effective amount of an compound having Formula I and/or Formula IV, or a salt or prodrug thereof, wherein Formula I and IV comprise: 
       
         
           
           
               
               
           
         
         wherein X is N, O Po, S, Se, or Te; 
         wherein Y is N or O; 
         wherein R 1  is H, C, lower alkyl, a lower alcohol, or CN; 
         wherein R 1  is H, C, lower alkyl, or a lower alcohol, or CN; 
         wherein n is 0 or 1; 
         wherein m is 0 or 1; 
         wherein k is 0, 1, 2, 3, or 4; and, 
         wherein p is 1 or 2; 
       
       
         
           
           
               
               
           
         
       
       wherein:
 X is N, O, P, Po, S, Se, Te, O—O, Po—Po, S—S, Se—Se, or Te—Te, 
 n and m are independently 0 or 1; and 
 wherein R 21  and R 22  are independently hydrogen, halo, cyano, phosphate, thio, alkyl, alkenyl, alkynyl, alkoxy, aminoalkyl, cyanoalkyl, hydroxyalkyl, haloalkyl, hydroxyhaloalkyl, alkylsulfonic acid, thiosulfonic acid, alkylthiosulfonic acid, thioalkyl, alkylthio, alkylthioalkyl, alkylaryl, carbonyl, alkylcarbonyl, haloalkylcarbonyl, alkylthiocarbonyl, aminocarbonyl, aminothiocarbonyl, alkylaminothiocarbonyl, haloalkylcarbonyl, alkoxycarbonyl, aminoalkylthio, hydroxyalkylthio, cycloalkyl, cycloalkenyl, aryl, aryloxy, heteroaryloxy, heterocyclyl, heterocyclyloxy, sulfonic acid, sulfonic alkyl ester, thiosulfate, or sulfonamido; and 
 Y is cyano, isocyano, amino, alkyl amino, aminocarbonyl, aminocarbonyl alkyl, alkylcarbonylamino, amidino, guanidine, hydrazino, hydrazide, hydroxyl, alkoxy, aryloxy, hetroaryloxy, cyloalkyloxy, carbonyloxy, alkylcarbonyloxy, haloakylcarbonyloxy, arylcarbonyloxy, carbonylperoxy, alkylcarbonylperoxy, arylcarbonylperoxy, phosphate, alkylphosphate esters, sulfonic acid, sulfonic alkyl ester, thiosulfate, thiosulfenyl, sulfonamide, —R 23 R 24 , wherein R 23  is S, SS, Po, Po—Po, Se, Se—Se, Te, or Te—Te, and R 24  is defined as for R 21  herein, or Y is 
 
       
         
           
           
               
               
           
         
         wherein X, R 21  and R 22 , are as defined herein. 
       
     
     
         68 .- 149 . (canceled) 
     
     
         150 . The method of  claim 67 , wherein X is sulfur. 
     
     
         151 . The method of  claim 67 , wherein said salt is a sulfide salt selected from the group consisting of sodium sulfide (Na 2 S), sodium hydrogen sulfide (NaHS), potassium sulfide (K 2 S) potassium hydrogen sulfide (KHS), lithium sulfide (Li 2 S), rubidium sulfide (Rb 2 S), cesium sulfide (Cs 2 S), ammonium sulfide ((NH 4 ) 2 S), ammonium hydrogen sulfide (NH 4 )HS, beryllium sulfide (BeS), magnesium sulfide (MgS), calcium sulfide (CaS), strontium sulfide (SrS), barium sulfide (BaS). 
     
     
         152 . The method of  claim 67 , wherein the compound is H 2 S, H 2 Se, H 2 Te, or H 2 Po. 
     
     
         153 . The method of  claim 152 , wherein the compound is H 2 S. 
     
     
         154 . The method of  claim 67 , wherein the compound is provided to the biological as a gas, semi-solid liquid, liquid, or solid. 
     
     
         155 . The method of  claim 67 , wherein the biological matter is a patient. 
     
     
         156 . The method of  claim 155 , wherein the patient is provided with the compound before, during, or after an injury, the onset or progression of a disease, or hemorrhaging in the patient. 
     
     
         157 . The method of  claim 156 , wherein the injury involves hemorrhaging. 
     
     
         158 . The method of  claim 154 , wherein the active compound is bubbled into a liquid. 
     
     
         159 . The method of  claim 154 , wherein the active compound is dissolved into the liquid. 
     
     
         160 . The method of  claim 155 , wherein the patient is provided the compound by administration to the biological matter intravenously, intradermally, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostatically, intrapleurally, intratracheally, intranasally, intrathecally, intravitreally, intravaginally, intrarectally, topically, intratumorally, intramuscularly, intraperitoneally, intraocularly, subcutaneously, subconjunctival, intravesicularlly, mucosally, intrapericardially, intraumbilically, intraocularally, orally, topically, locally, by inhalation, by injection, by infusion, by continuous infusion, by localized perfusion, via a catheter, or via a lavage. 
     
     
         161 . The method of  claim 160 , wherein the compound is administered to the patient intravenously. 
     
     
         162 . The method of  claim 161 , wherein the patient has a disease or adverse medical condition. 
     
     
         163 . The method of  claim 162 , wherein the disease or adverse medical condition is selected from the group consisting of hemorrhagic shock, myocardial infarction, cardiac arrest, ischemia/reperfusion injury, unstable angina, post-angioplasty, aneurysm, trauma, stroke, coronary artery bypass graft (CABG) surgery, and blood loss. 
     
     
         164 . The method of  claim 162 , wherein the patient is identified as in need of treatment.