Enterically coated cysteamine, cystamine and derivatives thereof

Abstract

The disclosure provides oral cysteamine and cystamine formulations useful for treating cystinosis and neurodegenerative diseases and disorders. The formulations provide controlled release compositions that improve quality of life and reduced side-effects.

1 - 24 . (canceled) 
     
     
         25 . A composition comprising cysteamine or cystamine, or pharmaceutically acceptable salts thereof, and one or more materials that provide increased delivery of cysteamine or cystamine to the small intestine, wherein the composition is formulated as a tablet or a capsule. 
     
     
         26 . The composition of  claim 25 , wherein the tablet or capsule further comprises a coating selected from the group consisting of polymerized gelatin, shellac, methacrylic acid copolymer type CNF, cellulose butyrate phthalate, cellulose hydrogen phthalate, cellulose proprionate phthalate, polyvinyl acetate phthalate (PVAP), cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate, dioxypropyl methylcellulose succinate, carboxymethyl ethylcellulose (CMEC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), and acrylic acid polymers and copolymers formed from methyl acrylate, ethyl acrylate, methyl methacrylate and/or ethyl methacrylate with copolymers of acrylic and methacrylic acid esters. 
     
     
         27 . The composition of  claim 25 , wherein the material increases delivery of the cystamine or cysteamine to a region of the gastrointestinal tract of a subject in which the pH is greater than pH 4.5. 
     
     
         28 . The composition of  claim 25 , wherein the material increases delivery of the cystamine or cysteamine to a region of the gastrointestinal tract of a subject in which the pH is between 4.5 and 6.5. 
     
     
         29 . The composition of  claim 25 , wherein the materials increase delivery to the proximal or mid-small intestine or both. 
     
     
         30 . The composition of  claim 25 , wherein the materials increase delivery to one or more of the duodenum, jejunum or mid-ileum. 
     
     
         31 . The composition of  claim 26 , wherein the coating material begins to dissolve in an aqueous solution at pH between about 4.5 to about 5.5. 
     
     
         32 . The composition of  claim 25 , wherein the composition is formulated as a tablet. 
     
     
         33 . The composition of  claim 32 , wherein the tablet further comprises a stabilizer. 
     
     
         34 . The composition of  claim 32 , wherein the tablet further comprises a filler. 
     
     
         35 . The composition of  claim 32 , wherein the tablet further comprises a binding agent. 
     
     
         36 . A method of administering cysteamine or cystamine, or pharmaceutically acceptable salts thereof, to a patient in need thereof comprising administering to said patient a pharmaceutical composition comprising cysteamine or cystamine, or pharmaceutically acceptable salts thereof, twice per day, wherein the composition increases delivery of cysteamine or cystamine, or pharmaceutically acceptable salts thereof, to the small intestine, wherein the cysteamine or cystamine is formulated as a tablet or capsule. 
     
     
         37 . The method of  claim 36 , wherein each dose of cysteamine or cystamine is about 0.5-1.0 g/m2. 
     
     
         38 . The method of  claim 36 , wherein the patient is suffering from cystinosis. 
     
     
         39 . The method of  claim 36 , wherein the patient is suffering from a neurodegenerative disease 
     
     
         40 . The method of  claim 36 , wherein the patient is in need of a hepato-protectant agent. 
     
     
         41 . A method of administering cysteamine or cystamine, or pharmaceutically acceptable salts thereof, to a patient in need thereof comprising administering to said patient a pharmaceutical composition comprising cysteamine or cystamine, or pharmaceutically acceptable salts thereof, wherein the composition increases delivery of cysteamine or cystamine, or pharmaceutically acceptable salts thereof, to the small intestine and wherein the frequency of administering is less than four times daily, wherein the cysteamine or cystamine is formulated as a tablet or capsule. 
     
     
         42 . The method of  claim 36  or  41 , wherein the composition increases delivery to the proximal or mid-small intestine or both. 
     
     
         43 . The method of  claim 36  or  41 , wherein the composition increases delivery to one or more of the duodenum, jejunum or mid-ileum. 
     
     
         44 . The method of  claim 36  or  41 , wherein the composition increases delivery to a region of the gastrointestinal tract of a subject in which the pH is greater than pH 4.5. 
     
     
         45 . The method of  claim 41 , wherein the patient is suffering from cystinosis. 
     
     
         46 . The method of  claim 41 , wherein the patient is suffering from a neurodegenerative disease. 
     
     
         47 . The method of  claim 46 , wherein the neurodegenerative disease is Huntington's disease or Parkinson's disease. 
     
     
         48 . The method of  claim 41 , further comprising treating the patient with a second therapeutic agent. 
     
     
         49 . The method of  claim 41 , wherein the patient is suffering from a metabolic disorder. 
     
     
         50 . The method of  claim 41 , wherein the patient is suffering from free radical damage. 
     
     
         51 . The method of  claim 36  or  41 , further comprising treating the patient with a second therapeutic agent.