Molecularly imprinted polymers for the treatment and diagnosis of medical conditions

Abstract

Improved molecularly imprinted polymers (MIPs) with both higher and more specific binding capacity for particular bile acids and/or salts, including the synthesis of such MIPs, the compounds themselves, and specific applications thereof. As an example of a particularly preferred specific application of these compounds, the present invention encompasses the use of the MIPs as sequestrants in the gastrointestinal tract, particularly in order to bind and therefore remove toxins from the gastrointestinal tract. In addition, the present invention is also useful for treatment of various diseases which are related to, and/or characterized by, an effect of bile acids and salts, such as atherosclerosis, liver disease and various diseases of the gastrointestinal tract. The MIP compounds of the present invention are also useful for combination therapy with other medications and for diagnosis and monitoring of diseases.

What is claimed is:  
     
         1 . A method for treating a subject for a disease selected from the group consisting of heart disease, gallstone disease, colorectal cancer, a precursor of colorectal cancer, gastroesophageal reflux diseases, esophageal cancer, COX-2 mediated inflammatory conditions and cholestatic liver disease, the method comprising: 
 orally administering a molecularly imprinted polymer to the subject.    
     
     
         2 . The method of  claim 1 , wherein the subject is treated for at least two of the above diseases concurrently.  
     
     
         3 . The method of  claim 1 , wherein said molecularly imprinted polymer is capable of binding to the toxin and sequestering the toxin.  
     
     
         4 . The method of  claim 3 , wherein said molecularly imprinted polymer comprises at least one functional monomer selected from the group consisting of: 2-, 3- and 4-vinyl-2-hydroxypyridine and N,N′-diethyl(4-vinylphenyl)amidine.  
     
     
         5 . The method of  claim 4 , wherein said molecularly imprinted polymer further comprises a cross-linking agent for cross-linking said at least one functional monomer, wherein said crosslinking agent is selected from the group consisting of ethyleneglycol dimethacrylate, N,N′-diacryloyl- or N,N′-dimethacryloyl ethylenediamine, N,N′-diacryloyl- or N,N′-dimethacryloyl 1,3-diaminobenzene, N,N′-diacryloyl- or N,N′-dimethacryloyl 1,4-diaminobenzene, a diacrylate or dimethacrylate of 1,2-, 1,3-, or 1,4-dihydroxybenzene, N,N′-(4-vinylbenzoyl)-1,ω-diaminoalkane, and an N,N′-diacryloyl- or N,N′-dimethacryloyl 1,ω-diaminoalkane.  
     
     
         6 . The method of  claim 3 , wherein the toxin comprises at least one bile acid or salt, or a combination thereof.  
     
     
         7 . A method for treating a subject for a heart disease, the method comprising: 
 administering a molecularly imprinted polymer (MIP) compound to the subject.    
     
     
         8 . The method of  claim 7 , wherein the heart disease is characterized by a condition selected from the group consisting of high cholesterol and oxidized LDL, or a combination thereof.  
     
     
         9 . The method of  claim 8 , wherein said molecularly imprinted polymer is capable of binding to the toxin and sequestering the toxin.  
     
     
         10 . The method of  claim 9 , wherein said molecularly imprinted polymer comprises at least one functional monomer selected from the group consisting of: 2-, 3- and 4-vinyl-2-hydroxypyridine and N,N′-diethyl(4-vinylphenyl)amidine.  
     
     
         11 . The method of  claim 10 , wherein said molecularly imprinted polymer further comprises a cross-linking agent for cross-linking said at least one functional monomer, wherein said crosslinking agent is selected from the group consisting of ethyleneglycol dimethacrylate, N,N′-diacryloyl- or N,N′-dimethacryloyl ethylenediamine, N,N′-diacryloyl- or N,N′-dimethacryloyl 1,3-diaminobenzene, N,N′-diacryloyl- or N,N′-dimethacryloyl 1,4-diaminobenzene, a diacrylate or dimethacrylate of 1,2-, 1,3-, or 1,4-dihydroxybenzene, N,N′-(4-vinylbenzoyl)-1,ω-diaminoalkane, and an N,N′-diacryloyl- or N,N′-dimethacryloyl 1,ω-diaminoalkane.  
     
     
         12 . The method of  claim 9 , wherein the toxin comprises at least one bile acid or salt, or a combination thereof.  
     
     
         13 . A method for treating a subject for a disease of the gastrointestinal tract, the method comprising the step of administering a molecularly imprinted polymer (MIP) compound to the subject.  
     
     
         14 . The method of  claim 13 , wherein the disease of the gastrointestinal tract is selected from the group consisting of colorectal cancer, a precursor to colorectal cancer, gastroesophageal disease, esophageal cancer, cholestatic liver disease and gallstone disease.  
     
     
         15 . A method for treating a subject for a disease characterized by a COX-2 mediated inflammatory condition, the method comprising the step of administering a molecularly imprinted polymer (MIP) compound to the subject.  
     
     
         16 . A method for performing combination therapy for treating a subject for a disease, the method comprising the step of administering a combination of a molecularly imprinted polymer (MIP) compound and at least one additional drug to the subject.  
     
     
         17 . The method of  claim 16 , wherein the disease is selected from the group consisting of heart disease, colorectal cancer, gastrointestinal reflux disease liver disease and a disease characterized by a Cox-2 mediated inflammation.  
     
     
         18 . The method of  claim 16 , wherein said at least one additional drug alters at least one of the level or composition of the bile in at least a portion of the body.  
     
     
         19 . The method of  claim 18 , wherein said at least one additional drug is selected from the group consisting of a non-specific toxic bile acid or salt sequestrant, ursodeoxycholic acid and bile acid or salt transport inhibitors.  
     
     
         20 . The method of  claim 16 , wherein said molecularly imprinted polymer is capable of binding to the toxin and sequestering the toxin.  
     
     
         21 . The method of  claim 20 , wherein said molecularly imprinted polymer comprises at least one functional monomer selected from the group consisting of: 2-, 3- and 4-vinyl-2-hydroxypyridine and N,N′-diethyl(4-vinylphenyl)amidine.  
     
     
         22 . The method of  claim 21 , wherein said molecularly imprinted polymer further comprises a cross-linking agent for cross-linking said at least one functional monomer, wherein said crosslinking agent is selected from the group consisting of ethyleneglycol dimethacrylate, N,N′-diacryloyl- or N,N′-dimethacryloyl ethylenediamine, N,N′-diacryloyl- or N,N′-dimethacryloyl 1,3-diaminobenzene, N,N′-diacryloyl- or N,N′-dimethacryloyl 1,4-diaminobenzene, a diacrylate or dimethacrylate of 1,2-, 1,3-, or 1,4-dihydroxybenzene, N,N′-(4-vinylbenzoyl)-1,ω-diaminoalkane, and an N,N′-diacryloyl- or N,N′-dimethacryloyl 1,ω-diaminoalkane.  
     
     
         23 . The method of  claim 22 , wherein the toxin comprises at least one bile acid or salt, or a combination thereof.