Systems and methods related to degradation of uremic toxins

Abstract

The present invention generally relates to the treatment of uremic toxins in vivo using uremic toxin-treating enzymes, and/or cells capable of producing uremic toxin-treating enzymes or otherwise reacting with uremic toxins. Non-limiting examples of cases where the treatment of uremic toxins is desired include renal disease or dysfunction, gout, subjects receiving chemotherapy, or the like. In one aspect, the treatment includes an oral delivery composition able to reduce the blood concentration of one or more non-protein nitrogen compounds in vivo. The composition, in some cases, may comprise one, two, or more uremic toxin-treating enzymes, such as urease, uricase or creatininase. The oral delivery composition may be able to deliver the uremic toxin-treating enzymes, substantially undigested, to the intestines, where the enzymes can interact with uremic toxins transported to the intestines from the bloodstream. In another aspect, the treatment includes an oral delivery composition comprising a cell able to reduce the concentration of one or more uremic toxins in vivo. In some cases, the cell may be designed to overexpress one, two, or more uremic toxin-treating enzymes, such as urease, uricase or creatininase, for example, by transfecting the cell with a corresponding gene. In some embodiments, a species able to react with or otherwise sequester by-products of the uremic toxin-treating enzyme reactions may be included with the oral delivery composition. For example, if the by-product is ammonium, the species may be a sorbent able to adsorb ammonium, an enzyme able to react with the ammonium, or the like.

1 - 98 . (canceled)  
     
     
         99 . A method, comprising: 
 administering, to a subject, an oral delivery composition comprising a capsule, wherein the capsule comprises an enteric coating comprising a polymer, and the capsule contains isolated urease and an ammonium uptake species in an effective amount to treat a disease characterized by elevated levels of at least one non-protein nitrogen compound.    
     
     
         100 . The method of  claim 99 , wherein the polymer comprises cellulose acetate.  
     
     
         101 . The method of  claim 99 , wherein the capsule, when ingested by the subject, does not substantially release the isolated urease externally of the capsule.  
     
     
         102 . The method of  claim 99 , wherein the capsule does not substantially impede mass transport of urea therethrough.  
     
     
         103 . The method of  claim 99 , wherein the ammonium uptake species is able to adsorb ammonium.  
     
     
         104 . The method of  claim 103 , wherein the ammonium uptake species comprises a sorbent.  
     
     
         105 . The method of  claim 104 , wherein the sorbent comprises zirconium phosphate.  
     
     
         106 . The method of  claim 104 , wherein the sorbent comprises at least one of carbon and oxystarch.  
     
     
         107 . The method of  claim 99 , wherein the ammonium uptake species comprises at least one enzyme able to react with ammonium.  
     
     
         108 . The method of  claim 99 , wherein the subject is susceptible to or exhibits symptoms of a disease characterized by elevated levels of at least one non-protein nitrogen compound.  
     
     
         109 . The method of  claim 108 , wherein the subject is susceptible to or exhibits symptoms of a disease characterized by elevated levels of more than one non-protein nitrogen compounds.  
     
     
         110 . The method of  claim 99 , wherein the subject has end stage renal disease.  
     
     
         111 . The method of  claim 99 , wherein the subject has renal dysfunction.  
     
     
         112 . The method of  claim 99 , wherein the subject has gout.  
     
     
         113 . The method of  claim 99 , wherein the subject has been treated with chemotherapy.  
     
     
         114 . The method of  claim 99 , further comprising administering dialysis to the subject.  
     
     
         115 . An article, comprising: 
 an oral delivery composition comprising a capsule comprising isolated urease and an ammonium uptake species, wherein the capsule comprises an enteric coating comprising a polymer.    
     
     
         116 . The article of  claim 115 , wherein the polymer comprises cellulose acetate.  
     
     
         117 . The article of  claim 115 , wherein the ammonium uptake species comprises a sorbent.  
     
     
         118 . The article of  claim 115 , wherein the sorbent comprises zirconium phosphate.