Controlled release preparation

Abstract

A controlled release preparation wherein the release of active ingredient is controlled, which releases an active ingredient for an extended period of time by staying or slowly migrating in the gastrointestinal tract, is provided by means such as capsulating a tablet, granule or fine granule wherein the release of active ingredient is controlled and a gel-forming polymer. Said tablet, granule or fine granule has a release-controlled coating-layer formed on a core particle containing an active ingredient.

1 . A capsule comprising a tablet, granule or fine granule and a gel-forming polymer, wherein a release of an active ingredient is controlled. 
     
     
         2 . The capsule according to  claim 1 , wherein the release of the active ingredient is controlled by a release-controlled coating-layer formed on a core particle containing the active ingredient. 
     
     
         3 . The capsule according to  claim 2 , wherein the release-controlled coating-layer contains a pH-dependently soluble polymer. 
     
     
         4 . The capsule according to  claim 2 , wherein the release-controlled coating-layer is a diffusion-controlled layer. 
     
     
         5 . The capsule according to  claim 1 , wherein the release of the active ingredient is controlled by dispersing the active ingredient into a release-controlled matrix composing the tablet, granule or fine granule. 
     
     
         6 . The capsule according to  claim 2 , wherein the tablet, granule or fine granule in which the release of the active ingredient is controlled has a disintegrant layer containing di sintegrant formed on the core particle containing the active ingredient and the release-controlled coating-layer formed on said disintegrant layer, and a release of the active ingredient is initiated after a certain lag time. 
     
     
         7 . The capsule according to  claim 1 , wherein the tablet, granule or fine granule in which the release of the active ingredient is controlled is coated with the gel-forming polymer. 
     
     
         8 . The capsule according to  claim 7  which further contains a gel-forming polymer. 
     
     
         9 . The capsule according to  claim 1 , which comprises two kinds of tablet, granule or fine granule having different release properties of the active ingredient. 
     
     
         10 . The capsule according to  claim 9 , which comprises the tablet, granule or fine granule having an enteric coat that releases the active ingredient at the pH of about 5.5 and the tablet, granule or fine granule having a release-controlled coating-layer that releases the active ingredient at the pH of about 6.0 or above. 
     
     
         11 . The capsule according to  claim 1 , wherein the gel-forming polymer is a polymer whose viscosity of 5% aqueous solution is about 3,000 mPa·s or more at 25° C. 
     
     
         12 . The capsule according to  claim 1 , wherein the gel-forming polymer is a polymer having molecular weight of 400,000 to 10,000,000. 
     
     
         13 . The capsule according to  claim 2 , wherein the release-controlled coating-layer is a layer containing one or more kinds of polymeric substances selected from the group consisting of hydroxypropylmethyl cellulose phthalate, cellulose acetate phthalate, carboxymethylethyl cellulose, methyl methacrylate-methacrylic acid copolymer, methacrylic acid-ethyl acrylate copolymer, ethyl acrylate-methyl methacrylate-trimethylammoniumethyl methacrylate chloride copolymer, methyl methacrylate-ethyl acrylate copolymer, methacrylic acid-methyl acrylate-methyl methacrylate copolymer, hydroxypropyl cellulose acetate succinate and polyvinyl acetate phthalate. 
     
     
         14 . The capsule according to  claim 13 , wherein the release-controlled coating-layer is comprised of 2 or more kinds of the layers. 
     
     
         15 . The capsule according to  claim 1 , wherein the release-controlled granule or fine granule has a particle size of about 100-1,500 μm. 
     
     
         16 . The capsule according to  claim 1 , wherein the active ingredient is a proton pump inhibitor (PPI). 
     
     
         17 . The capsule according to  claim 16 , wherein the PPI is an imidazole compound represented by formula (I′): 
       
         
           
           
               
               
           
         
       
       wherein ring C′ is an optionally substituted benzene ring or an optionally substituted aromatic monocyclic heterocyclic ring, R 0  is a hydrogen atom, an optionally substituted aralkyl group, acyl group or acyloxy group, R 1 , R 2  and R 3  are the same or different and are a hydrogen atom, an optionally substituted alkyl group, an optionally substituted alkoxy group or an optionally substituted amino group, and Y represents a nitrogen atom or CH; or a salt thereof or an optically active isomer thereof. 
     
     
         18 . The capsule according to  claim 17 , wherein the imidazole compound is lansoprazole. 
     
     
         19 . The capsule according to  claim 17 , wherein PPI is an optically active R-isomer of lansoprazole. 
     
     
         20 . The capsule according to any one of  claim 1 , wherein the gel-forming polymer is one or more kinds of substances selected from the group consisting of polyethylene oxide (PEO, molecular weight: 400,000-10,000,000), hydroxypropylmethyl cellulose (HPMC), carboxymethyl cellulose (CMC-Na), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose and carboxyvinyl polymer. 
     
     
         21 . The capsule according to any one of  claim 1 , wherein the gel-forming polymer is polyethylene oxide (molecular weight: 400,000-10,000,000). 
     
     
         22 . The capsule according to  claim 1 , wherein the gel-forming polymer is added as a powder, fine granule or granule. 
     
     
         23 . The capsule according to  claim 3 , wherein the pH-dependently soluble polymer is methyl methacrylate-methacrylic acid copolymer. 
     
     
         24 - 49 . (canceled)