Formulations for oral delivery of adsorbents in the gut

Abstract

The invention relates to a formulation for the delayed and controlled delivery of an adsorbent into the lower intestine of mammals. The formulation includes a carrageenan and an adsorbent, such as activated charcoal. The invention further relates to uses of this formulation, in particular to pharmaceutical uses. In one embodiment, the formulation is used to eliminate or reduce the side effects in the intestine, in particular in the colon, of pharmaceutical agents that are administered as a treatment for a disorder, but that have side effects when they reach the late ileum, the caecum or the colon.

1 - 22 . (canceled) 
     
     
         23 . A composition comprising an adsorbent mixed with carrageenan. 
     
     
         24 . The composition of  claim 23 , in the form of a pellet. 
     
     
         25 . The composition of  claim 23 , wherein the adsorbent is activated charcoal. 
     
     
         26 . The composition of  claim 23 , wherein the carrageenan is a kappa-carrageenan. 
     
     
         27 . The composition of  claim 23 , wherein the amount of carrageenan is between 5% and 25% by weight of the composition. 
     
     
         28 . A formulation comprising:
 a core containing a composition according to  claim 23 , and b) a layer of an external coating formed around the core such that the adsorbent is released from the formulation in a desired part of the intestine.   
     
     
         29 . The formulation of  claim 28 , wherein the desired part of the intestine is the lower part of the intestine. 
     
     
         30 . The formulation of  claim 28 , wherein the external coating is a pH-dependent enterosoluble polymer. 
     
     
         31 . The formulation of  claim 30 , wherein the pH-dependent enterosoluble polymer is selected from the group consisting of 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 copolymer, 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.   
     
     
         32 . The formulation of  claim 30 , wherein the polymer dissolves at a pH equal to 6.0 and above. 
     
     
         33 . The formulation of  claim 30 , wherein the pH-dependent polymer is selected in the group consisting of shellac, hydroxypropylmethylcellulose acetate succinate, hydroxypropylmethylcellulose phthalate, anionic copolymers based on methyl acrylate, methyl methacrylate and methacrylic acid, and methacrylic acid and methyl methacrylate copolymers (1:2 ratio). 
     
     
         34 . The formulation of  claim 28 , wherein the external coating is a mixture of methyl methacrylate and methacrylic acid, and methacrylic acid and ethyl acrylate copolymer, in a ratio between 99:1 and 80:20. 
     
     
         35 . The formulation of  claim 28 , wherein a further coating is provided between the core and the external pH-dependent layer, and wherein said further coating is selected from the group consisting of pH-dependent polymers, pH-independent water soluble polymers, pH-independent insoluble polymers, and mixtures of a pH-dependent polymer and a water insoluble, pH-independent polymer. 
     
     
         36 . The formulation of  claim 35 , wherein the pH-dependent polymer is selected from the group consisting of shellac-type polymers, anionic copolymers based on methylacrylate, methylmethacrylate and methacrylic acid, methacrylic acid and ethyl acrylate copolymer, hydroxypropyl methylcellulose phthalate (HPMCP), and hydroxypropylmethylcellulose acetate succinate (HPMCAS). 
     
     
         37 . The formulation of  claim 35 , wherein the pH-independent water soluble polymer is selected from the group consisting of PVP and high molecular weight cellulose polymers. 
     
     
         38 . The formulation of  claim 37 , wherein the high molecular weight cellulose polymers are selected from the group consisting of hydroxypropylmethylcellulose (HPMC) and hydroxypropylcellulose (HPC). 
     
     
         39 . The formulation of claim  13 , wherein the pH-independent insoluble polymers are selected from the group consisting of ethylcellulose polymers and ethyl acrylate methyl methacrylate copolymers. 
     
     
         40 . The formulation of  claim 35  wherein the mixtures of the pH-dependent polymer and the water insoluble, pH-independent polymer comprise ethylcellulose or ethyl acrylate methyl methacrylate copolymer (NE30D). 
     
     
         41 . The formulation according to  claim 34 , wherein the polymer layer that dissolves in a pH-independent manner comprises at least one cellulose derivative selected from the group consisting of hydroxypropylcellulose or ethylcellulose. 
     
     
         42 . The formulation according to  claim 34 , wherein the polymer layer that dissolves in a pH-independent manner is made of a 1:9 to 9:1 mixture of a methacrylic acid and ethyl acrylate copolymer and an ethyl acrylate methyl methacrylate copolymer. 
     
     
         43 . A method of eliminating or reducing the side effects in the intestine of pharmaceutical agents that are administered as a treatment for a disorder, but that have side effects when they, or a metabolite or derivative thereof, reach the late ileum, the caecum or the colon, comprising administering an effective amount of the formulation of  claim 28  to a patient in need of treatment thereof. 
     
     
         44 . The method of  claim 43 , wherein the method is used for eliminating or reducing the antibiotic-associated adverse effects of antibiotic agents. 
     
     
         45 . The method of  claim 44 , wherein the antibiotic-associated adverse effects of antibiotic agents include the emergence of antibiotic resistance or diarrhea. 
     
     
         46 . The method of  claim 43 , wherein the antibiotic and the formulation of claim  6  are administered simultaneously by the oral route. 
     
     
         47 . The method of  claim 43 , wherein said pharmaceutical agents are selected from the group consisting of antineoplastic agents, anti-inflammatory agents, interleukin-1 inhibitors, selective phosphodiesterase 4 inhibitors, compounds with anti-inflammatory and anti-mitotic activities, and metabolites thereof. 
     
     
         48 . The method of  claim 43 , wherein the method is used to eliminate the effects in the intestine of bacterial or fungal toxins before they reach the colon. 
     
     
         49 . The method of  claim 48 , wherein the toxins are mycotoxins, endotoxins, enterotoxins, or toxins produced by  Clostridium difficile.    
     
     
         50 . The method of  claim 43 , wherein the pharmaceutical agents are agents used to treat chronic kidney disease (CKD), inflammatory bowel diseases (IBDs), or hepatic encephalopathy. 
     
     
         51 . The method of  claim 43 , wherein the method is used to eliminate or reduce the amount of AGEs, phenols, indols, nitric oxide, oxygen radicals, prostaglandins, leucotrienes, histamine, proteases, matrix metallo proteinases or nitrogenous compounds, in the lower part of the intestine. 
     
     
         52 . The method of  claim 43 , wherein the method is used to reduce flatulence, stool smell, halitosis or food intolerance. 
     
     
         53 . The method of  claim 43 , wherein the method is used to treat pets or farm animals.