Methods for maintaining effective plasma concentrations of a pharmaceutical

Abstract

The present invention provides a sustained-release pharmaceutical composition, characterized in that there are contained tamsulosin or a pharmaceutically acceptable salt thereof and a carrier for a sustained-release pharmaceutical composition and the ratio (C min /C max ratio) of the plasma tamsulosin concentration at 24 hours after the administration of the preparation per os (C min ) to the maximum plasma tamsulosin concentration after the administration (C max ) is about 0.4 or more.

1 . A method for maintaining an effective plasma concentration of tamsulosin or a pharmaceutically acceptable salt thereof, said method comprising:
 orally administering a controlled-release preparation comprising:   a) tamsulosin or a pharmaceutically acceptable salt thereof;   b) a hydrophilic base having a solubility where the amount of water necessary for dissolving 1 g of the substrate is not more than 5 mL; and   c) a hydrogel-forming polymer having a viscosity of not less than 1000 cps and/or an average molecular weight of not less than 2,000,000,   wherein even for 8 to 24 hours after administration, said preparation releases tamsulosin to be absorbed in vivo; and   maintaining an effective plasma concentration of tamsulosin or a pharmaceutically acceptable salt thereof, said effective plasma concentration indicated by a ratio (C min /C max  ratio) of the plasma tamsulosin concentration at 24 hours after the administration of the preparation per os (C min ) to the maximum plasma tamsulosin concentration after the administration (C max ) being about 0.4 to less than about 1.   
     
     
         2 . The method according to  claim 1 , wherein the tamsulosin pharmaceutically acceptable salt is tamsulosin hydrochloride. 
     
     
         3 . The method according to  claim 1 , wherein the hydrophilic base is selected from the group consisting of polyethylene glycol 400, polyethylene glycol 1500, polyethylene glycol 4000, polyethylene glycol 6000, and polyethylene glycol 20,000. 
     
     
         4 . The method according to  claim 1 , wherein the hydrogel forming polymer is selected from the group consisting of hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose sodium, hydroxyethyl cellulose, a carboxyvinyl polymer, polyethylene oxide (PEO) and a mixture thereof. 
     
     
         5 . The method according to  claim 4 , wherein the hydrogel forming polymer is PEO having an average molecular weight of not less that 4,000,000. 
     
     
         6 . The method according to  claim 1 , wherein said preparation further comprises ferric oxide. 
     
     
         7 . The method according to  claim 1 , wherein the value of C min  normalized by the dose of tamsulosin or a pharmaceutically acceptable salt thereof is more than about 10×10 −6  mL −1 . 
     
     
         8 . The method according to  claim 1 , wherein the value of C min  is about 4 ng/mL or more. 
     
     
         9 . The method according to  claim 1 , wherein the value of C max  normalized by the dose of tamsulosin or a pharmaceutically acceptable salt thereof is about 40×10 −6  mL −1  or less. 
     
     
         10 . The method according to  claim 1 , wherein the value of C max  normalized by the dose of tamsulosin or a pharmaceutically acceptable salt thereof is about 30×10 −6  mL −1  or less. 
     
     
         11 . The method according to  claim 1 , wherein a value of C max  is about 20 ng/mL or less. 
     
     
         12 . A controlled-release preparation, said preparation comprising:
 a) tamsulosin or a pharmaceutically acceptable salt thereof;   b) a hydrophilic base having a solubility where the amount of water necessary for dissolving 1 g of the substrate is not more than 5 mL; and   c) a hydrogel-forming polymer having a viscosity of not less than 1000 cps and/or an average molecular weight of not less than 2,000,000.   
     
     
         13 . The controlled-release preparation according to  claim 12 , wherein the tamsulosin pharmaceutically acceptable salt is tamsulosin hydrochloride. 
     
     
         14 . The controlled-release preparation according to  claim 12 , wherein the hydrophilic base is selected from the group consisting of polyethylene glycol 400, polyethylene glycol 1500, polyethylene glycol 4000, polyethylene glycol 6000, and polyethylene glycol 20,000. 
     
     
         15 . The method according to  claim 12 , wherein the hydrogel forming polymer is selected from the group consisting of hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose sodium, hydroxyethyl cellulose, a carboxyvinyl polymer, polyethylene oxide (PEO) and a mixture thereof. 
     
     
         16 . The controlled-release preparation according to  claim 15 , wherein the hydrogel forming polymer is PEO having an average molecular weight of not less that 4,000,000. 
     
     
         17 . The controlled-release preparation according to  claim 12 , further comprising ferric oxide. 
     
     
         18 . A method for maintaining an effective plasma concentration of tamsulosin or a pharmaceutically acceptable salt thereof, said method comprising:
 orally administering a controlled-release pharmaceutical composition, said composition comprising:   a) a water-soluble, hydrogel-forming polymer matrix in a concentration of about 10% to about 90% by weight; and   b) tamsulosin, or a pharmaceutically acceptable salt thereof, uniformly dispersed in said matrix, wherein even for 8 to 24 hours after administration, said composition still releases tamsulosin to be absorbed in vivo; and   maintaining an effective plasma concentration of tamsulosin or a pharmaceutically acceptable salt thereof, said effective plasma concentration indicated by a ratio (C min /C max  ratio) of the plasma tamsulosin concentration at 24 hours after the administration of the preparation per os (C min ) to the maximum plasma tamsulosin concentration after the administration (C max ) being about 0.4 to less than about 1 in said individual to reduce postural hypotension.   
     
     
         19 . The method according to  claim 18 , wherein the tamsulosin pharmaceutically acceptable salt is tamsulosin hydrochloride. 
     
     
         20 . The method according to  claim 18 , wherein the polymer matrix comprises a polymer selected from the group consisting of hydroxypropylmethyl cellulose (HPMC), hydroxymethyl cellulose, hydroxyethylcellulose, carboxymethyl cellulose, ethyl cellulose, methylcellulose, carboxyvinyl polymer and a mixture thereof. 
     
     
         21 . The method according to  claim 18 , wherein the value of C min  normalized by the dose of tamsulosin or a pharmaceutically acceptable salt thereof is more than about 10×10 −6  mL −1 . 
     
     
         22 . The method according to  claim 18 , wherein the value of C min  is about 4 ng/mL or more. 
     
     
         23 . The method according to  claim 18 , wherein the value of C max  normalized by the dose of tamsulosin or a pharmaceutically acceptable salt thereof is about 40×10 −6  mL −1  or less. 
     
     
         24 . The method according to  claim 18 , wherein the value of C max  normalized by the dose of tamsulosin or a pharmaceutically acceptable salt thereof is about 30×10 −6  mL −1  or less. 
     
     
         25 . The method according to  claim 18 , wherein the value of C max  is about 20 ng/mL or less. 
     
     
         26 . A controlled-release pharmaceutical composition, said composition comprising:
 a) a water-soluble, hydrogel-forming polymer matrix in a concentration of about 10% to about 90% by weight; and   b) tamsulosin, or a pharmaceutically acceptable salt thereof, uniformly dispersed in said matrix.   
     
     
         27 . The controlled-release pharmaceutical composition according to  claim 26 , wherein the tamsulosin pharmaceutically acceptable salt is tamsulosin hydrochloride. 
     
     
         28 . The controlled-release pharmaceutical composition according to  claim 26 , wherein the polymer matrix comprises a polymer selected from the group consisting of hydroxypropylmethyl cellulose (HPMC), hydroxymethyl cellulose, hydroxyethylcellulose, carboxymethyl cellulose, ethyl cellulose, methylcellulose, carboxyvinyl polymer and a mixture thereof. 
     
     
         29 . The controlled-release pharmaceutical composition according to  claim 26 , wherein the polymer matrix comprises hydroxypropylmethyl cellulose.