Bipolar trans carotenoid salts and their uses

Abstract

The invention relates to trans carotenoid salt compounds, methods for making them, methods for solubilizing them and uses thereof. These compounds are useful in improving diffusivity of oxygen between red blood cells and body tissues in mammals including humans.

1 .- 8 . (canceled) 
     
     
         9 . A method of solubilizing a BTCS having the structure
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton 
   comprising the steps of:   a) preparing a dilute solution of sodium carbonate or sodium bicarbonate,   b) adding said dilute solution to deionized water to raise the pH to 7 or above,   c) adding a BTCS to the solution of step b).   
     
     
         10 . A method of solubilizing a BTCS having the structure
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton 
   comprising the steps of:   a) adding a BTCS to a saline solution,   b) removing undissolved material.   
     
     
         11 . A method of solubilizing a BTCS having the structure
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and, 
 TCRO=trans carotenoid skeleton. 
   comprising the steps of:   a) adding a base to water to make a basic solution,   c) adding a BTCS to said solution.   
     
     
         12 . A method of solubilizing a BTCS having the structure
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton 
   comprising the steps of:   a) preparing deionized water,   b) adding a BTCS to the solution of step a).   
     
     
         13 . A method as in  claim 9 , 10 , 11  or  12  wherein said compound is trans sodium crocetinate. 
     
     
         14 . A method of increasing the diffusivity of oxygen in a mammal comprising administering to a mammal a therapeutically effective amount of a compound having the formula:
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton, 
   wherein said compound is not TSC.   
     
     
         15 . A method as in  claim 14  wherein said administration is by inhalation. 
     
     
         16 . A method of treating respiratory disease comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula:
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and p 2  TCRO=trans carotenoid skeleton, 
   wherein said compound is not TSC.   
     
     
         17 . A method of treating emphysema comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton, 
   wherein said compound is not TSC.   
     
     
         18 . A method of treating hemorrhagic shock comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton, 
   wherein said compound is not TSC.   
     
     
         19 . A method of treating cardiovascular disease comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton, 
   wherein said compound is not TSC.   
     
     
         20 . A method of treating atherosclerosis comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton, 
   wherein said compound is not TSC.   
     
     
         21 . A method of treating asthma comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton, 
   wherein said compound is not TSC.   
     
     
         22 . A method of treating spinal cord injuries comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton, 
   wherein said compound is not TSC.   
     
     
         23 . A method of treating cerebral edema comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton, wherein said compound is not TSC. 
   
     
     
         24 . A method of treating papillomas comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton, 
   wherein said compound is not TSC.   
     
     
         25 . A method of treating hypoxia comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton, 
   wherein said compound is not TSC.   
     
     
         26 .- 39 . (canceled) 
     
     
         40 . A method of increasing the diffusivity of oxygen in a mammal comprising administering to a mammal by inhalation a therapeutically effective amount of TSC. 
     
     
         41 . An inhaler containing a BTCS compound having the structure:
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton. 
   
     
     
         42 . An inhaler as in  claim 40  wherein said BTCS compound is TSC. 
     
     
         43 . A method of converting an isomeric mixture of olefinic dialdehydes into the all trans aldehyde comprising isomerizing said isomeric mixture of dialdehydes with a sulfinic acid in a solvent. 
     
     
         44 . A method as in  claim 43  wherein said sulfinic acid has the formula RSO2H where R is C1 through C10 straight or branched alkyl group or an aryl group. 
     
     
         45 . A method as in  claim 43  where the solvent is selected from the group consisting of 1,4-dioxane, tetrahydrofuran or dialkyl ether wherein the alkyl group is a C1 through C10 straight or branched alkyl group. 
     
     
         46 . A method as in claim wherein said sulfinic acid is para-toluenesulfinic acid and said solvent is 1,4-dioxane. 
     
     
         47 . A method as in  claim 43  wherein said olefinic dialdehyde is 2,7-dimethyl-2,4,6-ocatrienedial. 
     
     
         48 . A method as in  claim 43  wherein said olefinic dialdehyde is 2,7-dimethyl-2,4,6-ocatrienedial, said sulfinic acid is para-toluenesulfinic acid and said solvent is 1,4-dioxane. 
     
     
         49 . A method of treating ischemia comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula:
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton, 
   wherein said compound is not TSC.   
     
     
         50 . A method of treating traumatic brain injury comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton, 
   wherein said compound is not TSC.   
     
     
         51 . A method of enhancing performance of a mammal comprising administering to said mammal a therapeutically effective amount of a compound having the formula:
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton. 
   
     
     
         52 . A method of treating complications of diabetes comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton. 
   
     
     
         53 . A method of treating Alzheimer's disease comprising administering to a mammal in need of treatment a therapeutically effective amount of a compound having the formula
   YZ-TCRO—ZY
   where:
 Y=a cation 
 Z=a polar group which is associated with the cation, and 
 TCRO=trans carotenoid skeleton. 
   
     
     
         54 .- 59 . (canceled)