Pharmaceutical formulations of amyloid inhibiting compounds

Abstract

Therapeutic formulations and methods for inhibiting amyloid deposition in a subject, whatever its clinical setting, are described. Therapeutic formulations and methods for preventing or treating amyloidosis and/or amyloid-related disease are also described.

1 - 6 . (canceled)  
     
     
         7 . A method of treating or preventing an amyloid-related disease in a subject comprising administering to a subject a therapeutic amount of a therapeutic formulation comprising a therapeutic compound formulated to significantly reduce or prevent gastrointestinal intolerance, such that the amyloid-related disease is treated or prevented.  
     
     
         8 - 9 . (canceled)  
     
     
         10 . The method of  claim 7 , wherein the amyloid-related disease is selected from the group consisting of Alzheimer's disease, cerebral amyloid angiopathy, inclusion body myositis, macular degeneration, Down's syndrome, Mild Cognitive Impairment, and hereditary cerebral hemorrhage.  
     
     
         11 . The method of  claim 7 , wherein the amyloid-related disease is Alzheimer's disease type II diabetes.  
     
     
         12 - 14 . (canceled)  
     
     
         15 . The method of  claim 7 , wherein the therapeutic compound is a substituted or unsubstituted alkylsulfonic acid, substituted or unsubstituted alkylsulfuric acid, substituted or unsubstituted alkylthiosulfonic acid, substituted or unsubstituted alkylthiosulfuric acid, or a pharmaceutically acceptable salt thereof.  
     
     
         16 - 19 . (canceled)  
     
     
         20 . The method of  claim 7 , wherein the therapeutic compound has the following structure  
       
         
           
           
               
               
           
         
       
       where Y is —NR a R b  or —SO 3   − X + , wherein n is an integer from 1 to 5; X +  is hydrogen or a cationic group; and R a  and R b  are each independently selected from the group consisting of hydrogen, alkyl, aryl, or heterocyclyl, or R a  and R b , taken together with the nitrogen atom to which they are attached, form a cyclic moiety having from 3 to 8 atoms in the ring.  
     
     
         21 . (canceled)  
     
     
         22 . The method of  claim 7 , wherein the therapeutic compound is 3-amino-1-propanesulfonic acid.  
     
     
         23 . The method of  claim 7 , wherein the therapeutic formulation is formulated as described in Example 1, Example 2, Example 3, or Example 4.  
     
     
         24 . The method of  claim 7 , wherein the therapeutic compound is administered orally.  
     
     
         25 - 42 . (canceled)  
     
     
         43 . The method of  claim 7 , wherein the therapeutic compound is administered with an agent selected from the group consisting of an agent that modifies the release of the therapeutic compound, a glidant/diluent, a filler, a binder/desintegrant, a lubricant, a subcoat, a topcoat, an enteric coat, and any combination thereof.  
     
     
         44 - 54 . (canceled)  
     
     
         55 . A pharmaceutical composition for treating or preventing an amyloid-related disease comprising a therapeutic formulation comprising a therapeutic compound formulated to significantly reduce or prevent gastrointestinal intolerance, in an amount sufficient to prevent or treat an amyloid-related disease in a subject, and a pharmaceutically acceptable vehicle.  
     
     
         56 . (canceled)  
     
     
         57 . The pharmaceutical composition of  claim 55 , wherein the amyloid-related disease is selected from the group consisting of Alzheimer's disease, cerebral amyloid angiopathy, inclusion body myositis, macular degeneration, Down's syndrome, Mild Cognitive Impairment, and hereditary cerebral hemorrhage.  
     
     
         58 . The pharmaceutical composition of  claim 57  wherein the amyloid-related disease is Alzheimer's disease diabetes.  
     
     
         59 - 62 . (canceled)  
     
     
         63 . The pharmaceutical composition of  claim 55 , wherein the therapeutic compound is a substituted or unsubstituted alkylsulfonic acid, substituted or unsubstituted alkylsulfuric acid, substituted or unsubstituted alkylthiosulfonic acid, substituted or unsubstituted alkylthiosulfuric acid, or a pharmaceutically acceptable salt thereof.  
     
     
         64 - 67 . (canceled)  
     
     
         68 . The pharmaceutical composition of  claim 55 , wherein the therapeutic compound has the following structure  
       
         
           
           
               
               
           
         
       
       where Y is —NR a R b  or —SO 3   − X + , wherein n is an integer from 1 to 5; X +  is hydrogen or a cationic group; and R a  and R b  are each independently selected from the group consisting of hydrogen, alkyl, aryl, or heterocyclyl, or R a  and R b , taken together with the nitrogen atom to which they are attached, form a cyclic moiety having from 3 to 8 atoms in the ring.  
     
     
         69 . (canceled)  
     
     
         70 . The pharmaceutical composition of  claim 55 , wherein the therapeutic compound is 3-amino-1-propanesulfonic acid.  
     
     
         71 . The pharmaceutical composition of  claim 55 , wherein the therapeutic formulation is formulated as described in Example 1, Example 2, Example 3, or Example 4.  
     
     
         72 . The pharmaceutical composition of  claim 70 , wherein the therapeutic formulation is formulated with an agent selected from the group consisting of an agent that modifies the release of the therapeutic compound, a glidant/diluent, a filler, a binder/desintegrant, a lubricant, a subcoat, a topcoat, an enteric coat, and any combination thereof.  
     
     
         73 . The pharmaceutical composition of  claim 72 , wherein the agent that modifies the release of the therapeutic compound is hydroxypropylmethylcellulose (HPMC).  
     
     
         74 . The pharmaceutical composition of  claim 72 , wherein the glidant/diluent is silicated mycrocrystalline.  
     
     
         75 . The pharmaceutical composition of  claim 72 , wherein the filler is dibasic calcium phosphate.  
     
     
         76 . The pharmaceutical composition of  claim 72 , wherein the binder/desintegrant is Starch 1500.  
     
     
         77 . The pharmaceutical composition of  claim 72 , wherein the lubricant is stearic acid powder.  
     
     
         78 . The pharmaceutical composition of  claim 72 , wherein the lubricant is magnesium stearate.  
     
     
         79 . The pharmaceutical composition of  claim 72 , wherein the subcoat is Opadry® II White.  
     
     
         80 . The pharmaceutical composition of  claim 72 , wherein the topcoat is Opadry® II White or Opadry® Clear.  
     
     
         81 . The pharmaceutical composition of  claim 72 , wherein the enteric coat is Acryleze®.  
     
     
         82 - 89 . (canceled)  
     
     
         90 . The method of  claim 7 , wherein the amyloid-related disease is cerebral amyloid angiopathy.  
     
     
         91 - 101 . (canceled)  
     
     
         102 . A pharmaceutical formulation comprising greater than 5% by weight of 3-amino-1-propanesulfonic acid.  
     
     
         103 - 108 . (canceled)  
     
     
         109 . The pharmaceutical formulation of  claim 102  further comprising greater than 1% by weight of an additional agent.  
     
     
         110 - 113 . (canceled)  
     
     
         114 . The pharmaceutical formulation of  claim 109 , wherein the additional agent is an enteric-coating or an agent that modifies the release of the therapeutic compound.  
     
     
         115 - 121 . (canceled)  
     
     
         122 . The method of  claim 7  wherein the therapeutic compound is formulated with an enteric-coating, or an agent that modifies the release of the therapeutic compound.  
     
     
         123 - 125 . (canceled)  
     
     
         126 . A method of preventing, treating or inhibiting Alzheimer's disease in a subject, comprising administering to the subject an effective amount of a therapeutic formulation comprising a therapeutic compound formulated to significantly reduce or prevent gastrointestinal intolerance, such that Alzheimer's disease is prevented, treated, or inhibited.  
     
     
         127 . A packaged pharmaceutical composition for treating Alzheimer's disease in a subject, comprising a container holding a therapeutically effective amount of a therapeutic formulation comprising a therapeutic compound formulated to significantly reduce or prevent gastrointestinal intolerance; and instructions for using the compound for treating Alzheimer's disease in a subject.  
     
     
         128 . The method of  claim 126 , wherein the therapeutic compound is 3-amino-1-propanesulfonic acid.  
     
     
         129 . A pharmaceutical composition for preventing, treating or inhibiting Alzheimer's disease in a subject comprising a therapeutic formulation comprising a therapeutic compound formulated to significantly reduce or prevent gastrointestinal intolerance, in an amount sufficient to prevent, treat or inhibit Alzheimer's disease in a subject, and a pharmaceutically acceptable vehicle.  
     
     
         130 . The pharmaceutical composition of  claim 129 , wherein the therapeutic compound is 3-amino-1-propanesulfonic acid.  
     
     
         131 . The method of  claim 7 , wherein the therapeutic formulation comprises a therapeutic compound having the formula 3-amino-1-propanesulfonate/X in an amount sufficient to prevent or treat an amyloid-related disease, wherein X is a counter cation or forms an ester with the sulfonate, wherein the ester or counter cation includes alcohol radicals or positively charged atoms and moieties, respectively, that do not significantly affect the ability of the therapeutic formulation to reduce or prevent gastrointestinal intolerance.  
     
     
         132 . The pharmaceutical composition of  claim 55 , wherein the therapeutic formulation comprises a therapeutic compound having the formula 3-amino-1-propanesulfonate/X in an amount sufficient to prevent or treat an amyloid-related disease, and a pharmaceutically acceptable vehicle, wherein X is a counter cation or forms an ester with the sulfonate, wherein the ester or counter cation includes alcohol radicals or positively charged atoms and moieties, respectively, which do not significantly affect the ability of the therapeutic formulation to reduce or prevent gastrointestinal intolerance.  
     
     
         133 . The pharmaceutical composition of  claim 55 , wherein the therapeutic compound is formulated with an enteric-coating or an agent that modifies the release of the therapeutic compound.