Controlled release compositions of agents that reduce circulating levels of platelets and methods therefor

Abstract

Provided are prophylactic and therapeutic methods of treatment of subjects for the purpose of inhibiting vaso-occlusive events, including embolism, by administering agents, including anagrelide and anagrelide derivatives, which reduce the number of circulating platelets to low normal or to below normal levels. Methods and pharmaceutical preparations comprising such agents are provided.

1 . A composition, comprising:
 a solid support core of a substantially water soluble, swellable or insoluble material, wherein the solid support is from 85-95% by weight of the composition;   an optional preparatory coat, wherein the preparatory coat is from 0-5% by weight of the composition;   a substrate layer comprising a binder and a platelet number reducing agent in the form of microparticles, wherein:
 the platelet number reducing agent is present in a form that has a shelf stability of at least three months and is in an amount that is from 0.01-0.6% or 0.05-0.45% or 0.075-0.35% by weight of the composition or 10 ng to 10 mg or 50 μg to 10 mg or 50 μg to 1000 μg; 
 at least 90% of the microparticles are 25 microns or less; and 
 the binder is present at a weight of 0.1-5% by weight of the composition; 
   a release control component effective for controlled release of the platelet number reducing agent, wherein the release control component is present at a weight of 0-10% by weight of the composition; and   an optional finishing coat and/or enteric coating, wherein the finishing coat and/or enteric coating is present at a weight of 0.25-10% by weight of the composition.   
     
     
         2 .- 44 . (canceled) 
     
     
         45 . A method for reducing platelet count in a subject, comprising:
 administering to a subject a controlled release composition of  claim 1 , wherein:   the composition delivers an amount of the platelet number reducing agent effective to reduce platelet count in the subject by at least 10% of pre-treatment levels.   
     
     
         46 .- 65 . (canceled)