Anti-methanogenic compositions and uses thereof

Abstract

The present invention relates to, in part, methods and compositions for the treatment of methanogen-associated disorders such as, for example, Irritable Bowel Syndrome (IBS). Particularly, modified-release formulations comprising at least one antimethanogenic statin are provided which release the antimethanogenic statin in the intestines.

1 . A modified-release formulation comprising at least one antimethanogenic statin, wherein the formulation releases at least 60% of the antimethanogenic statin after the stomach and into one or more regions of the intestinal tract. 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The formulation of  claim 1 , wherein the antimethanogenic statin is selected from atorvastatin, cerivastatin, dalvastatin, eptastatin, fluindostatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, velostatin, and pharmaceutically acceptable salts, stereoisomers, or prodrug derivatives thereof. 
     
     
         5 . The formulation of  claim 1 , wherein the antimethanogenic statin is lovastatin and pharmaceutically acceptable salts, stereoisomers, or prodrug derivatives thereof. 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . The formulation of  claim 1 , wherein the antimethanogenic statin is released in the small intestine, the duodenum, jejunum, the ileum, the ileocecal junction, the large intestine or combinations thereof. 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . The formulation of  claim 1 , wherein the antimethanogenic statin is released one or more of the cecum, ascending, transverse, descending or sigmoid portions of the colon, and rectum. 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . The formulation of  claim 1 , wherein the formulation comprises a modified-release coating that is substantially stable in gastric fluid, or a modified-release coating that is degraded by a microbial enzyme present in the gut flora. 
     
     
         17 . (canceled) 
     
     
         18 . The formulation of  claim 1 , wherein the formulation comprises a modified-release coating having a solubility that is pH-dependent, or wherein the formulation comprises a modified-release coating having a time-dependent erosion profile. 
     
     
         19 . (canceled) 
     
     
         20 . The formulation of  claim 1 , comprising:
 a first dose of at least one antimethanogenic statin; and   a second dose of at least one antimethanogenic statin; and   wherein the first dose and the second dose of at least one antimethanogenic statin are released at different times and/or at different pHs.   
     
     
         21 - 60 . (canceled) 
     
     
         61 . The formulation of  claim 20 , wherein the first and/or second dose of at least one antimethanogenic statin is encapsulated in a core particle. 
     
     
         62 . The formulation of  claim 20 , wherein a modified-release coating is disposed over the core particle to form a modified-release particle, or wherein the formulation comprises a plurality of modified-release particles. 
     
     
         63 . The formulation of  claim 20 , wherein the first and/or second dose of at least one antimethanogenic statin are encapsulated in a layer. 
     
     
         64 . The formulation of  claim 63 , wherein a modified-release coating is disposed over the layer to form a modified-release layer. 
     
     
         65 . The formulation of  claim 20 , wherein the formulation comprises a plurality of layers. 
     
     
         66 . The formulation of  claim 20 , wherein the first dose of at least one antimethanogenic statin is released at the duodenum, and the second dose of at least one antimethanogenic statin is released at the ileum. 
     
     
         67 . The formulation of  claim 20 , wherein the first dose of at least one antimethanogenic statin is released at the small intestine, and the second dose of at least one antimethanogenic statin is released at the large intestine. 
     
     
         68 . The formulation of  claim 20 , wherein the modified-release coating is substantially stable in gastric fluid, is degraded by a microbial enzyme present in the gut flora, has a solubility that is pH-dependent, or has a time-dependent erosion profile. 
     
     
         69 . A method of inhibiting or reducing methanogenesis in a human subject in need thereof, comprising administering a formulation  claim 1  to the subject. 
     
     
         70 . The method of  claim 69 , wherein the subject suffers from irritable bowel syndrome. 
     
     
         71 . The method of  claim 70 , wherein the subject suffers from, constipation constipation-associated IBS (IBS-C), the subject suffers from obesity, or the subject suffers from diabetes. 
     
     
         72 . A method of reducing or eliminating enteric methane production comprising administering a formulation of  claim 1  to a subject in need thereof.