Composition for the treatment of disease

Abstract

A composition for use in the treatment of a condition or disorder related to mucosal barrier dysfunction in the gut, the composition comprising activated carbon. The condition may be, for example, pouchitis or proctitis.

1 . A composition for use in the treatment of a condition or disorder related to mucosal barrier dysfunction in the gut, the composition comprising activated carbon, wherein:
 (A) the composition is for oral administration and comprises:
 (a) a core comprising activated carbon; 
 (b) a first layer around the core, the first layer comprising an insoluble semipermeable material; and 
 (c) a second layer around the first layer which breaks down rapidly at a predetermined pH and/or which dissolves at a predetermined location in the gastrointestinal tract; 
   Or (B) the composition is for rectal administration and comprises a dry powder of activated carbon of particle size 0.001 to 1 mm.   
     
     
         2 . A composition according to  claim 1  for use in the treatment of proctitis, radiation proctitis, or pouchitis. 
     
     
         3 . A composition according to  claim 1  or  claim 2 , the composition comprising a dry powder of activated carbon of particle size 0.02 to 1 mm, wherein the composition is for administration (to be administered) rectally as a dry powder. 
     
     
         4 . A composition according to any preceding claim wherein the activated carbon is of average particle size 0.05 mm to 1 mm, for example average particle size 0.15 mm to 1 mm, for example 0.15 mm to 0.3 mm. 
     
     
         5 . A composition according to any preceding claim comprising 450 μg to 10 g activated carbon. 
     
     
         6 . A composition according to any preceding claim comprising granular activated carbon. 
     
     
         7 . A composition for use in the treatment of proctitis (e.g. radiation proctitis) or pouchitis, the composition comprising a dry powder of activated carbon of particle size 0.02 to 1 mm, wherein the composition is for administration (to be administered) rectally as a dry powder. 
     
     
         8 . A composition according to  claim 1  for oral administration, the composition comprising:
 (a) a core comprising activated carbon; 
 (b) a first layer around the core, the first layer comprising an insoluble semipermeable material; and 
 (c) a second layer around the first layer which dissolves at a predetermined pH. 
 
     
     
         9 . A composition according to  claim 1  or  8  wherein the core is activated carbon. 
     
     
         10 . A composition according to  claim 1 ,  8  or  9  wherein the activated carbon is sanded or deburred. 
     
     
         11 . A composition according to  claim 1 ,  8 ,  9  or  10  wherein the activated carbon is of particle size 0.02 to 5.0 mm, for example of particle size 0.6 to 1.2 mm. 
     
     
         12 . A composition according to  claim 1 ,  8 ,  9 ,  10  or  11  wherein the insoluble semipermeable material comprises one or more of ethyl cellulose, glycerylmonostearate, cellulose acetate butyrate, dipolylactic acid, polyvinyl chloride, and a poly(meth)acrylate polymer such as EUDRAGIT® RL 100, EUDRAGIT® RL PO, EUDRAGIT® RL 30D, EUDRAGIT® RL 12.5, EUDRAGIT® RS 100, EUDRAGIT® RS PO, EUDRAGIT® RS 30D, EUDRAGIT® RS 12.5, EUDRAGIT® NE 30D, EUDRAGIT® NE 40D. 
     
     
         13 . A composition according to  claim 1 ,  8 ,  9 ,  10 ,  11  or  12  wherein the first layer further comprises a water soluble material. 
     
     
         14 . A composition according to  claim 1 ,  8 ,  9 ,  10 ,  11 ,  12  or  13  wherein the first layer further comprises a water soluble material comprising hydroxypropylmethyl cellulose (HPMC). 
     
     
         15 . A composition according to  claim 1 ,  8 ,  9 ,  10 ,  11 ,  12 ,  13  or  14  wherein the water soluble material is mixed with the insoluble semipermeable material. 
     
     
         16 . A composition according to  claim 1 ,  8 ,  9 ,  10 ,  11 ,  12 ,  13 ,  14  or  15  wherein the water soluble material comprises 0.1 to 30% by weight of the amount of the insoluble semipermeable material, for example 2 to 25% by weight of the amount of the insoluble semipermeable material. 
     
     
         17 . A composition according to  claim 1 ,  8 ,  9 ,  10 ,  11 ,  12 ,  13 ,  14 ,  15  or  16  wherein the second layer comprises a material which dissolves at pH 5 to pH 7. 
     
     
         18 . A composition according to  claim 1 ,  8 ,  9 ,  10 ,  11 ,  12 ,  13 ,  14 ,  15 ,  16  or  17  wherein the second layer is an enteric layer comprising a material which remains substantially intact at pH 1 to 4.9, but which breaks down rapidly at pH 5 to 7. 
     
     
         19 . A composition according to  claim 1 ,  8 ,  9 ,  10 ,  11 ,  12 ,  13 ,  14 ,  15 ,  16 ,  17  or  18  wherein the second layer is selected from Hypromellose-Acetate-Succinate, cellulose acetate trimellitate (CAT), cellulose acetate phthalate (CAP), anionic copolymers based on methylacrylate, methylmethacrylate and methacrylic acid, hydroxypropyl methylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose acetate succinate (HPMCAS), methacrylic acid and ethyl acrylate copolymers, methacrylic acid and ethyl acrylate copolymers, methacrylic acid and methyl methacrylate copolymers (1:1 ratio), methacrylic acid and methyl methacrylate copolymers (1:2 ratio), Polyvinyl acetate phthalate (PVAP) and Shellac resins. 
     
     
         20 . A composition according to any preceding claim wherein the activated carbon is the sole active pharmaceutical ingredient. 
     
     
         21 . A composition for use according to  claim 1  comprising:
 (a) a core comprising activated carbon; 
 (b) a first layer around the core, the first layer comprising an insoluble semipermeable material in the form of ethyl cellulose, and optionally further comprising a water soluble material comprising hydroxypropylmethylcellulose (HPMC); 
 (c) a second layer comprising hydroxypropylmethylcellulose acetate succinate (HPMC AS). 
 
     
     
         22 . A method of treatment of proctitis or pouchitis comprising a step of administering (to a subject in need thereof) a pharmaceutically effective amount of a composition comprising activated carbon. 
     
     
         23 . A method according to  claim 22  comprising a step of administering a pharmaceutically effective amount of a composition comprising a dry powder (a dry dose) of activated carbon of particle size 0.02 to 1 mm, preferably 0.05 to 1 mm. 
     
     
         24 . A method according to  claim 22  or  23 , in which the step of administering comprises administering the composition rectally as a dry powder. 
     
     
         25 . A method according to  claim 22  wherein the step of administration comprises oral administration of a composition as defined in any of  claims 8  to  21 . 
     
     
         26 . A composition for use in the treatment of proctitis, the composition comprising activated carbon. 
     
     
         27 . A dry powder (a dry dose) of activated carbon of particle size 0.02 to 1 mm for use in the treatment of proctitis or pouchitis, or for use in the manufacture of a pharmaceutical composition for the treatment of proctitis or pouchitis.