Methods and compositions 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.

What is claimed: 
     
         1 . A pharmaceutical composition comprising Formula I or IV, or salt thereof and a pharmaceutically acceptable excipient, wherein Formula I and IV comprise: 
       
         
           
           
               
               
           
         
         wherein X is Se; 
         wherein Y is N or O; 
         wherein R 1  is H, C, lower alkyl, a lower alcohol, or CN; 
         wherein R 2  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 Se or Se—Se; 
         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 Se or Se—Se, and R 24  is defined as for R 21  herein, or Y is 
       
       
         
           
           
               
               
           
         
         wherein X, R 21  and R 22 , are as defined herein. 
       
     
     
         2 . A method for enhancing survivability comprising providing to a subject in need thereof an effective amount of the pharmaceutical composition according to  claim 1 . 
     
     
         3 . The method of  claim 2 , wherein said chalcogenide is H 2 Se. 
     
     
         4 . A method of reducing cellular damage due to a disease or adverse medical condition, comprising providing to a subject in need thereof an effective amount of the pharmaceutical composition according to  claim 1 . 
     
     
         5 . The method of  claim 4 , wherein said pharmaceutical composition is a liquid. 
     
     
         6 . The method of  claim 4 , wherein said pharmaceutical composition is a gas. 
     
     
         7 . The method of  claim 4 , 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. 
     
     
         8 . A method of protecting biological matter from an injury, the onset or progression of a disease, or death comprising providing to the matter, before the injury, the onset or progression of a disease, or death, an effective amount of thereof an effective amount of the pharmaceutical composition according to  claim 1 , wherein the effective amount is less than an amount that can induce stasis in the biological matter. 
     
     
         9 . An article of manufacture comprising packaging material and, contained within the packaging material thereof, the pharmaceutical composition according to  claim 1 , wherein the packaging material comprises a label that indicates that the pharmaceutical composition can be used for inducing stasis in in vivo biological matter. 
     
     
         10 . A method of reducing cellular damage from a surgery, comprising providing to a subject in need thereof an effective amount of the pharmaceutical composition according to  claim 1 . 
     
     
         11 . A method for treating hemorrhagic shock in a patient comprising providing an effective amount of the pharmaceutical composition according to  claim 1 . 
     
     
         12 . The method of  claim 11 , wherein pharmaceutical composition is provided to the patient using a nebulizer. 
     
     
         13 . The method of  claim 11 , wherein the patient is provided with more than 3,000 ppm of Formula I. 
     
     
         14 . The method of  claim 11 , wherein the patient is provided with Formula I for about five minutes or less. 
     
     
         15 . A method of enhancing survivability under hypoxic or ischemic conditions, comprising providing to a subject in need thereof the pharmaceutical composition of  claim 1 . 
     
     
         16 . The method of  claim 15 , wherein the pharmaceutical composition comprises H 2 Se. 
     
     
         17 . The method of  claim 15 , wherein the ischemic or hypoxic condition is due to myocardial infarction, stroke, blood loss, coronary artery bypass graft (CABG) surgery, or angioplasty. 
     
     
         18 . A method for enhancing survivability of biological matter comprising providing to the matter to an effective amount of i) the pharmaceutical composition of  claim 1  and ii) hypoxic conditions. 
     
     
         19 . A method for enhancing survivability of biological matter comprising providing to the matter an effective amount the pharmaceutical composition of  claim 1 . 
     
     
         20 . A method for enhancing survivability of biological matter comprising administering to the matter an effective amount the pharmaceutical composition of  claim 1 . 
     
     
         21 . A method for preventing or reducing damage to biological matter under adverse conditions comprising providing to the biological matter an effective amount of the pharmaceutical composition of  claim 1 , wherein damage is prevented or reduced. 
     
     
         22 . A method for creating a preserved stock of organisms comprising exposing the organisms to an effective amount the pharmaceutical composition of  claim 1 . 
     
     
         23 . A method of protecting biological matter from an injury, the onset or progression of a disease, or death comprising providing to the matter, before the injury, the onset or progression of a disease, or death, an effective amount the pharmaceutical composition of  claim 1 , wherein the effective amount is less than an amount that can induce stasis in the biological matter and wherein the biological matter is hemorrhaging. 
     
     
         24 . A method of preventing an organism from bleeding to death comprising providing to the bleeding organism an effective amount of the pharmaceutical composition of  claim 1  to prevent death. 
     
     
         25 . The method of  claim 24 , wherein the organism goes into hemorrhagic shock. 
     
     
         26 . A method for inducing stasis in biological matter comprising:
 a. identifying biological matter in which stasis is desired; and,   b. providing to the biological matter an effective amount of the pharmaceutical composition of  claim 1  to induce stasis of the in vivo biological matter.   
     
     
         27 . The method of  claim 26 , wherein the biological matter is provided with an effective amount of a combination of different active compounds. 
     
     
         28 . An article of manufacture comprising packed together: the pharmaceutical composition of  claim 1 , instructions for use of the pharmaceutical composition, comprising: (a) identifying in vivo tissue in need of stasis treatment; and (b) administering an effective amount of the pharmaceutical composition to the in vivo biological matter. 
     
     
         29 . An article of manufacture comprising a medical gas comprising the pharmaceutical composition of  claim 1  and details or use and administration for inducing stasis in a biological matter. 
     
     
         30 . The method of  claim 29 , wherein the medical procedure is selected from elective surgery, planned surgery, or emergency surgery. 
     
     
         31 . The method of  claim 29 , wherein the pharmaceutical composition is administered intravenously. 
     
     
         32 . The method of  claim 29 , wherein the pharmaceutical composition is administrated by inhalation. 
     
     
         33 . The method of  claim 29 , wherein the surgery is cardiopulmonary surgery.