Trans carotenoids, their synthesis, formulation and uses

Abstract

The invention relates to trans carotenoid compounds and salts thereof as well as compositions thereof, methods for making 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 - 75 . (canceled) 
     
     
         76 . A method of treating a cancer of the pancreas in a mammal comprising:
 a) administering to the mammal a bipolar trans carotenoid salt having the formula:
   YZ-TCRO-ZY 
   where:   Y=a cation which can be the same or different,   Z=a polar group which can be the same or different and which is associated with the cation, and   TCRO=a linear trans carotenoid skeleton with conjugated carbon-carbon double bonds and single bonds, and having pendant groups X, wherein the pendant groups X, which can be the same or different, are a linear or branched hydrocarbon group having 10 or less carbon atoms, or a halogen; and   b) administering to the mammal chemotherapy, wherein said bipolar trans carotenoid salt is administered prior to administration of said chemotherapy and wherein the absorbency of the highest peak which occurs in the visible wavelength range of the bipolar trans carotenoid salt divided by the absorbency of the peak which occurs in the UV wavelength range is greater than 7.0.   
     
     
         77 . A method as in  claim 76 , wherein the method further comprises administering radiation to said mammal. 
     
     
         78 . A method of treating a cancer of the brain in a mammal comprising
 a) administering to the mammal a bipolar trans carotenoid salt having the formula:
   YZ-TCRO-ZY 
   where:   Y=a cation which can be the same or different,   Z=a polar group which can be the same or different and which is associated with the cation, and   TCRO=a linear trans carotenoid skeleton with conjugated carbon-carbon double bonds and single bonds, and having pendant groups X, wherein the pendant groups X, which can be the same or different, are a linear or branched hydrocarbon group having 10 or less carbon atoms, or a halogen, and   b) administering to the mammal radiation therapy, wherein said bipolar trans carotenoid salt is administered prior to administration of said radiation therapy and wherein the absorbency of the highest peak which occurs in the visible wavelength range of the bipolar trans carotenoid salt divided by the absorbency of the peak which occurs in the UV wavelength range is greater than 7.0.   
     
     
         79 . A method as in  claim 78 , wherein the method further comprises administering chemotherapy to said mammal. 
     
     
         80 . A method of treating cancer in a mammal comprising:
 a) administering to the mammal a bipolar trans carotenoid salt having the formula:
   YZ-TCRO-ZY 
   where:   Y=a cation which can be the same or different,   Z=a polar group which can be the same or different and which is associated with the cation, and   TCRO=a linear trans carotenoid skeleton with conjugated carbon-carbon double bonds and single bonds, and having pendant groups X, wherein the pendant groups X, which can be the same or different, are a linear or branched hydrocarbon group having 10 or less carbon atoms, or a halogen, and   b) administering to the mammal radiation therapy, and   c) administering to the mammal chemotherapy,   wherein said bipolar trans carotenoid salt is administered prior to administration of said radiation therapy and administration of said chemotherapy and wherein the absorbency of the highest peak which occurs in the visible wavelength range of the bipolar trans carotenoid salt divided by the absorbency of the peak which occurs in the UV wavelength range is greater than 7.0.   
     
     
         81 . A method as in  claim 80 , wherein the cancer is selected from the group consisting of squamous cell carcinomas, melanomas, lymphomas, sarcomas, sarcoids, osteosarcomas, skin cancer, breast cancer, head and neck cancer, gynecological cancer, urological and male genital cancer, bladder cancer, prostate cancer, bone cancer, cancers of the endocrine glands, cancers of the alimentary canal, cancers of the major digestive glands/organs, CNS cancer, and lung cancer. 
     
     
         82 . A method as in  claim 76 , wherein the bipolar trans carotenoid salt is trans sodium crocetinate (TSC) having the structure: 
       
         
           
           
               
               
           
         
         and is in the form of a lyophilized composition with a cyclodextrin. 
       
     
     
         83 . A method as in  claim 78 , wherein the bipolar trans carotenoid salt is trans sodium crocetinate (TSC) having the structure: 
       
         
           
           
               
               
           
         
         and is in the form of a lyophilized composition with a cyclodextrin. 
       
     
     
         84 . A method as in  claim 80 , wherein the bipolar trans carotenoid salt is trans sodium crocetinate (TSC) having the structure: 
       
         
           
           
               
               
           
         
         and is in the form of a lyophilized composition with a cyclodextrin.