Pharmaceutical preparations and methods to manage weight and to modulate the gut microbiota

Abstract

A pharmaceutical preparation, comprising: A) A plurality of particles, each particle comprising: 1) a core comprising at least one agent that increases oxygen tension and/or redox potential and/or pH in the colon of a subject following administration to the subject, and 2) an enteric coating encasing the core; and B) a capsule or sachet encasing the plurality of particles. Methods of weight management for a subject, comprising administering the pharmaceutical preparation to a subject in need thereof.

1 - 41 . (canceled) 
     
     
         42 . A composition comprising a plurality of particles, each particle comprising:
 1) a core comprising an oxygen-releasing agent, and   2) an enteric coating encasing the core.   
     
     
         43 . The composition of  claim 42 , wherein the composition comprises a capsule or sachet encasing the plurality of particles. 
     
     
         44 . The composition of  claim 43 , wherein the oxygen-releasing agent is characterized in that it increases the oxygen tension of a solution of phosphate buffered saline. 
     
     
         45 . The composition of  claim 43 , wherein the composition is characterized in that it achieves release of oxygen when assayed in PBS buffer at pH 7.4 after immersion at pH 1.2 for 2 hours. 
     
     
         46 . The composition of  claim 44  or  45 , wherein enteric coating dissolves at a pH above 5.5, 5.6, 6.0, 6.5, 6.8, 7.0, or 7.4. 
     
     
         47 . The composition of  claim 44  or  45 , wherein enteric coating dissolves at a pH between 6.8 and 7.2. 
     
     
         48 . The composition of  claim 44  or  45 , wherein enteric coating dissolves at a pH above 7.0. 
     
     
         49 . The composition of  claim 44  or  45 , wherein enteric coating comprises Eudragit FS 30D or Eudragit S100. 
     
     
         50 . The composition of  claim 44  or  45 , wherein the enteric coating comprises methacrylic acid copolymers, polyvinyl acetate phthalate, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, or hydroxypropyl methylcellulose acetylsuccinate. 
     
     
         51 . The composition of  claim 44  or  45 , wherein the enteric coating comprises a solid powder of an anionic copolymer matrix based on methacrylic acid and methyl methacrylate. 
     
     
         52 . The composition of  claim 44  or  45 , wherein the composition is characterized in that, when orally administered to a human subject, at least 50% of the oxygen-releasing agent is released over a period of 4 hours after contacting the small intestine. 
     
     
         53 . The composition of  claim 44  or  45 , wherein the oxygen-releasing agent comprises a peroxide. 
     
     
         54 . The composition of  claim 53 , wherein the peroxide is selected from the group consisting of:
 (i) hydrogen peroxide;   (ii) an organic peroxide selected from acetyl acetone peroxide, acetyl benzoyl peroxide, ascaridole, benzoyl peroxide, di-(1-naphthoyl)peroxide, diacetyl peroxide, ethyl hydroperoxide, ergesterol peroxide, and methyl isobutyl ketone peroxide;   (iii) an inorganic peroxide selected from ammonium persulfate, calcium peroxide, magnesium peroxide, Potassium persulfate, and sodium percarbonate; and   (iv) carbamide peroxide.   
     
     
         55 . The composition of  claim 53 , wherein the peroxide is selected from carbamide peroxide and sodium percarbonate. 
     
     
         56 . The composition of  claim 42 , wherein the oxygen-releasing agent comprises sodium percarbonate. 
     
     
         57 . The composition of  claim 44  or  45 , wherein the composition does not comprise an enzyme that oxidizes ethanol to acetate. 
     
     
         58 . The composition of  claim 44  or  45 , wherein the composition does not comprise an enzyme that catalyzes decomposition of hydrogen peroxide. 
     
     
         59 . The composition of  claim 44  or  45 , wherein the composition does not comprise catalase. 
     
     
         60 . The composition of  claim 44  or  45 , wherein the cores of the particles have a maximum dimension of from 0.1 to 2 mm. 
     
     
         61 . The composition of  claim 44  or  45 , wherein the cores of the particles have a maximum dimension of from 0.2 to 1.0 mm. 
     
     
         62 . The composition of  claim 44  or  45 , wherein the particles have a maximum dimension of 3.0 mm or less. 
     
     
         63 . The composition of  claim 44  or  45 , wherein the composition comprises from 25 to 500 mg of the oxygen-releasing agent. 
     
     
         64 . The composition of  claim 44  or  45 , wherein the composition comprises from 50 to 200 mg of the oxygen-releasing agent. 
     
     
         65 . The composition of  claim 44  or  45 , wherein the composition comprises a dose of 5 mg to 100 mg of hydrogen peroxide equivalent. 
     
     
         66 . The composition of  claim 44  or  45 , wherein the composition comprises a dose of 20 mg to 40 mg of hydrogen peroxide equivalent. 
     
     
         67 . The composition of  claim 44  or  45 , wherein the weight ratio of the enteric coating to the core of the particles is from 5% to 50%. 
     
     
         68 . The composition of  claim 44  or  45 , wherein the particles comprise a subcoat layer that encases the core and is disposed between the core and the enteric coating. 
     
     
         69 . The composition of  claim 68 , wherein the subcoat layer comprises a release rate modifier. 
     
     
         70 . The composition of  claim 68 , wherein the subcoat layer comprises HPMC. 
     
     
         71 . The composition of  claim 44  or  45 , wherein the composition is formulated for oral administration and release of the oxygen-releasing agent from the particles in the human small intestine and/or colon. 
     
     
         72 . The composition of  claim 44  or  45 , wherein the composition is formulated for oral administration and release of the oxygen-releasing agent from the particles in the human ileum. 
     
     
         73 . The composition of  claim 44  or  45 , wherein the composition is formulated for oral administration and release of the oxygen-releasing agent from the particles in the human distal ileum. 
     
     
         74 . The composition of  claim 44  or  45 , wherein the composition is formulated for oral administration and release of oxygen from the particles in the human small intestine and/or colon. 
     
     
         75 . The composition of  claim 44  or  45 , wherein the composition is formulated for oral administration and release of oxygen from the particles in the human ileum. 
     
     
         76 . The composition of  claim 44  or  45 , wherein the composition is formulated for oral administration and release of oxygen from the particles in the human distal ileum.