US2012095099A1PendingUtilityA1

Trans carotenoids, their synthesis, formulation and uses

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Assignee: GAINER JOHN LPriority: Feb 24, 2005Filed: Aug 5, 2011Published: Apr 19, 2012
Est. expiryFeb 24, 2025(expired)· nominal 20-yr term from priority
A61P 9/06A61P 43/00A61P 9/12A61P 3/06A61P 9/00A61P 35/00A61P 25/02A61P 25/00A61P 25/28A61P 29/00A61K 9/19A61N 5/10C07C 69/602A61K 31/202C07C 57/13A61K 31/11C07C 57/03A61K 41/0038A61K 45/06C07C 59/185C07F 1/04C07C 69/52
54
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Claims

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.

Claims

exact text as granted — not AI-modified
1 . A compound having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         2 . A compound having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         3 . A compound having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         4 . A compound having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         5 . A compound having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         6 . A compound having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         7 . A compound having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . A lyophilized composition of a bipolar trans carotenoid. 
     
     
         25 . A composition as in  claim 24  wherein the bipolar trans carotenoid is TSC. 
     
     
         26 . A method of synthesizing a BTCS 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, 
   comprising the steps of:   coupling a symmetrical dialdehyde containing conjugated carbon-carbon double bonds with a Wittig agent, and   saponifying the product of the coupling step.   
     
     
         27 . A method as in  claim 26  wherein the product of the coupling step is reacted with a second Wittig agent. 
     
     
         28 . A method as in  claim 26  wherein the symmetrical dialdehyde containing conjugated carbon-carbon double bonds is a C10 or C20 dial. 
     
     
         29 . A method as in  claim 26  wherein the coupling reaction is made in a pH neutral solvent system. 
     
     
         30 . A method as in  claim 29  wherein said pH neutral system is a butylene oxide solvent system. 
     
     
         31 . A method as in  claim 29  wherein said pH neutral system includes toluene, or methylene chloride/sodium hydroxide and sodium ethylate or sodium methylate. 
     
     
         32 . A method as in  claim 26  wherein the Wittig agent is a triphenylphosphorane. 
     
     
         33 . A method as in  claim 32  wherein the Wittig agent is [3-carbomethoxy-2-buten-1-ylidene]triphenylphosphorane. 
     
     
         34 . A method as in  claim 26  wherein the Wittig agent is a triphenyl phosphonium bromide or triphenyl phosphonium chloride or a mixture of the two. 
     
     
         35 . A method as in  claim 34  wherein the Wittig agent is D (2-(Ethoxycarbonyl)-2-buten-4-yl-triphenyl-phosphoniumbromide). 
     
     
         36 . A method as in  claim 26  wherein the Wittig agent is a C2, C3, C5, C10 or C15 Wittig ester halogenide. 
     
     
         37 . A method as in  claim 26  wherein the Wittig agent is a C2, C3, or C5 phosphonoester. 
     
     
         38 . A method as in  claim 37  wherein the phosphonoester is triphenyl phosphono acetate. 
     
     
         39 . A method as in  claim 26  wherein the coupling of step is made using butylene oxide as the solvent system. 
     
     
         40 . A method as in  claim 26  wherein after the coupling step is the step of isolating the desired product of the coupling reaction. 
     
     
         41 . A method as in  claim 26  wherein the product is saponified using a solution of NaOH, LiOH, KOH and methanol, ethanol or isopropanol as the solvent. 
     
     
         42 . A method as in  claim 26  wherein the product of the coupling step is saponified using NaOH and ethanol. 
     
     
         43 . A method as in  claim 26  wherein the product of the coupling step is saponified using a solution of NaOH and methanol. 
     
     
         44 . A method as in  claim 26  wherein the step of saponifying the product of the coupling step comprises the steps of:
 a) solubilizing the coupling product in ethanol, and 
 b) mixing the solution of step a) with a base. 
 
     
     
         45 . A method as in  claim 44  wherein the base is selected from the group consisting of NaOH, KOH, and LiOH. 
     
     
         46 . A method as in  claim 44  wherein the coupling product is saponified using ethanol and NaOH. 
     
     
         47 . A method as in  claim 26  wherein after the saponifying step, the desired product is washed with ethanol. 
     
     
         48 . A method as in  claim 26  wherein after the saponifying step, the desired product is washed with water. 
     
     
         49 . A method as in  claim 26  wherein the desired product is TSC. 
     
     
         50 . A method of synthesizing a BTC compound having the formula
   YZ-TCRO-ZY   where:
 Y=H 
 Z=a polar group which is associated with the H, and 
 TCRO=trans carotenoid skeleton, 
   comprising the steps of:   coupling a symmetrical dialdehyde containing conjugated carbon-carbon double bonds with a Wittig agent.   
     
     
         51 . A method as in  claim 50  wherein the coupling reaction is made in a pH neutral solvent system. 
     
     
         52 . A method as in  claim 51  wherein said pH neutral system is a butylene oxide solvent system. 
     
     
         53 . A method as in  claim 51  wherein said pH neutral system includes toluene, or methylene chloride/sodium hydroxide and sodium ethylate or sodium methylate. 
     
     
         54 . A method as in  claim 50  wherein the Wittig agent is a triphenylphosphorane. 
     
     
         55 . A method as in  claim 54  wherein the Wittig agent is [3-carbomethoxy-2-buten-1-ylidene]triphenylphosphorane. 
     
     
         56 . A method as in  claim 50  wherein the Wittig agent is a triphenyl phosphonium bromide or triphenyl phosphonium chloride or a mixture thereof. 
     
     
         57 . A method as in  claim 50  wherein the Wittig agent is a C5 Wittig ester halogenide. 
     
     
         58 . A method as in  claim 50  wherein the Wittig agent is D (2-(Ethoxycarbonyl)-2-buten-4-yl-triphenyl-phosphoniumbromide). 
     
     
         59 . A method as in  claim 50  wherein the coupling of step is made using butylene oxide as the solvent system. 
     
     
         60 . A method as in  claim 50  wherein after the coupling step is the step of isolating the desired product of the coupling reaction. 
     
     
         61 . A method as in  claim 60  wherein the desired product is washed with ethanol. 
     
     
         62 . A method as in  claim 60  wherein the desired product is washed with water. 
     
     
         63 . A method as in  claim 50  wherein the desired product is crocetin. 
     
     
         64 . (canceled) 
     
     
         65 . (canceled) 
     
     
         66 . (canceled) 
     
     
         67 . (canceled) 
     
     
         68 . (canceled) 
     
     
         69 . (canceled) 
     
     
         70 . (canceled) 
     
     
         71 . A method of treating hypertension in a mammal comprising administering to the mammal in need of treatment an amount of a trans carotenoid sufficient to reduce the hypertension. 
     
     
         72 . A method of treating ventricular fibrillations or tachycardia in a mammal comprising administering to a mammal in need of treatment an amount of a trans carotenoid sufficient to stop the ventricular fibrillations or tachycardia. 
     
     
         73 . A compound having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         74 . A compound selected from the group consisting of TPC and TLC. 
     
     
         75 . A compound selected from the group consisting of Compounds AA and CC.

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