Oral sustained-release preparation of fasudil hydrochloride

Abstract

Disclosed is an oral sustained-release preparation which contains at least one active-ingredient selected from the group consisting of fasudil hydrochloride and a hydrate thereof, the preparation comprising at least one sustained-release coated particle comprising a core having a surface and a coating formed on the surface of the core, wherein the core contains the active ingredient and the coating comprises a coating base material and a specific insoluble auxiliary material, and wherein the preparation exhibits, with respect to the active ingredient, a specific dissolution rate, as measured by the dissolution test. By using the oral sustained-release preparation of the present invention, it becomes possible to surely control the release of fasudil hydrochloride from the preparation, so that the effect of the active ingredient is maintained for a long period of time. Therefore, the burden of the patient who has to take the preparation can be decreased and the compliance with respect to the administration of the preparation can be improved. Also disclosed is a method for evaluating an oral sustained-release preparation containing the active ingredient, wherein the evaluation is conducted with respect to the sustained-release ability of the active ingredient.

1 . An oral sustained-release preparation of fasudil, wherein the preparation is sufficient when administered once to maintain a concentration in the blood of an active metabolite of fasudil in a desired range for a period of time between about two hours and at least about twelve hours after administering the preparation.  
   
   
       2 . The oral sustained-release preparation of  claim 1 , wherein the concentration in the blood of the active metabolite is at least about 20 ng/ml.  
   
   
       3 . The oral sustained-release preparation of  claim 1 , wherein the preparation comprises a coated particle comprising fasudil.  
   
   
       4 . The oral sustained-release preparation of  claim 3 , wherein the coated particle comprises a core having a surface and a coating formed on the surface, wherein the core comprises the fasudil.  
   
   
       5 . The oral sustained-release preparation of  claim 4 , wherein the amount of fasudil in the core_is at least about 30% by weight of the fasudil in_the preparation.  
   
   
       6 . The oral sustained-release preparation of  claim 5 , wherein the coating comprises a coating base material and an insoluble auxiliary material.  
   
   
       7 . The oral sustained-release preparation of  claim 6 , wherein the coating base material comprises a pharmaceutically acceptable hydrophobic polymer or a hydrophilic polymer capable of forming a coating.  
   
   
       8 . The oral sustained-release preparation of  claim 7 , wherein the hydrophobic polymer is selected from the group consisting of ethylcellulose, cellulose acetate and a copolymer of ethyl acrylate/methyl methacrylate/trimethylammonioethyl methacrylate chloride.  
   
   
       9 . The oral sustained-release preparation of  claim 6 , wherein the insoluble auxiliary material is selected from the group consisting of magnesium stearate, calcium stearate, talc, titanium oxide and light anhydrous silicic acid.  
   
   
       10 . An oral sustained-release preparation for providing a vasodilative activity to a mammal in need thereof, wherein the preparation comprises a coated particle comprising fasudil, and wherein the preparation provides a reliable therapeutic effect by providing a frequency of administration of not more than twice a day and maintaining a concentration in the blood of active metabolite in a desired range for a period of between about 2 hours and at least about twelve hours after administration.  
   
   
       11 . The oral sustained-release preparation of  claim 10 , wherein the coated particle comprises a core having a surface and a coating formed on the surface, wherein the core comprises the fasudil.  
   
   
       12 . The oral sustained-release preparation of  claim 11 , wherein the fasudil present in the core is_at least about 30% by weight of the fasudil in_the preparation.  
   
   
       13 . The oral sustained-release preparation of  claim 12 , wherein the coating comprises a coating base material and an insoluble auxiliary material.  
   
   
       14 . The oral sustained-release preparation of  claim 13 , wherein the coating base material comprises a pharmaceutically acceptable hydrophobic polymer or a hydrophilic polymer capable of forming a coating.  
   
   
       15 . The oral sustained-release preparation of  claim 14 , wherein the hydrophobic polymer is selected from the group consisting of ethylcellulose, cellulose acetate and a copolymer of ethyl acrylate/methyl methacrylate/trimethylammonioethyl methacrylate chloride.  
   
   
       16 . The oral sustained-release preparation of  claim 13 , wherein the insoluble auxiliary material is selected from the group consisting of magnesium stearate, calcium stearate, talc, titanium oxide and light anhydrous silicic acid.  
   
   
       17 . An oral sustained-release preparation of fasudil, wherein the preparation is sufficient when administered once to maintain a desired concentration of active metabolite in the blood for a period of between about two hours and at least about twelve hours after administration, wherein the desired concentration is at least about one third of a maximal concentration of active metabolite reached in the blood during said period.  
   
   
       18 . An oral sustained-release preparation comprising fasudil, wherein the preparation exhibits a dissolution rate of fasudil into 900 ml of distilled water at 37±0.50° C. with a paddle revolution rate of 100±4 rpm of about 5 to 40% by weight after 3 hours, and when administered once to a mammal, the preparation provides a concentration of an active metabolite of fasudil in the blood within a desired range for a period of between about two hours and at least about twelve hours after administration.  
   
   
       19 . A method for treating a mammal having an ischemic condition, comprising administering the oral sustained-release preparation according to  claim 1 .  
   
   
       20 . A method for maintaining a concentration in the blood of an active metabolite of fasudil of at least about 20 ng/ml for a period of between about 2 hours and at least about twelve hours after administering a single dose of the fasudil, comprising administering said dose in the form of an oral sustained-release preparation comprising a coated particle comprising the fasudil.