Canagliflozin monohydrate and its crystalline forms, preparation methods and uses thereof

Abstract

The present invention relates to canagliflozin Monohydrate and its crystalline forms. Compared to the prior art, canagliflozin Monohydrate and its crystalline forms have higher stability in water or aqueous system, is more suitable for wet granulation processes or suspension preparations and have good storage stability. The present invention also relates to preparation methods of canagliflozin Monohydrate and its crystalline forms, pharmaceutical compositions thereof and uses thereof in preparation of drugs for treating diseases such as diabetes, diabetes complications, obesity and so on.

What is claimed is: 
     
         1 . A method of treating type II diabetes comprising administering to a patient in need of treatment, an oral dosage form comprising a therapeutically effective amount of canagliflozin monohydrate. 
     
     
         2 . The method according to  claim 1 , wherein the therapeutically effective amount of canagliflozin monohydrate is in the range of 0.1 to 30 mg/kg/d. 
     
     
         3 . The method according to  claim 2 , wherein the therapeutically effective amount of canagliflozin monohydrate is about 100 mg. 
     
     
         4 . The method according to  claim 2 , wherein the therapeutically effective amount of canagliflozin monohydrate is about 300 mg. 
     
     
         5 . The method according to  claim 1 , wherein the oral dosage form is a tablet. 
     
     
         6 . The method according to  claim 5 , wherein the tablet is a delayed-release tablet. 
     
     
         7 . The method according to  claim 5 , wherein the tablet is a controlled-release tablet. 
     
     
         8 . The method according to  claim 1 , wherein canagliflozin monohydrate is in crystalline form. 
     
     
         9 . A delayed-release tablet comprising canagliflozin monohydrate and one or more polymers selected from the group consisting of hydroxypropyl cellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, ethyl cellulose, methacrylic polymer, and starch. 
     
     
         10 . The delayed-release tablet according to  claim 9 , wherein canagliflozin monohydrate is in crystalline form. 
     
     
         11 . A controlled-release tablet comprising canagliflozin monohydrate and one or more polymers selected from the group consisting of hydroxypropyl cellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, ethyl cellulose, methacrylic polymer, and starch. 
     
     
         12 . The controlled-release tablet according to  claim 11 , wherein canagliflozin monohydrate is in crystalline form. 
     
     
         13 . The method according to  claim 1 , wherein the oral dosage form further comprises an active pharmaceutical ingredient selected from the group consisting of an antidiabetic agent, an anti-hyperglycemic agent, an anti-obesity agent, an antihypertensive agent, an antiplatelet agent, an anti-atherosclerotic agent, and a hypolipidemic agent. 
     
     
         14 . The method according to  claim 13 , wherein the active pharmaceutical ingredient is an antidiabetic agent. 
     
     
         15 . The method according to  claim 13 , wherein the active pharmaceutical ingredient is an anti-hyperglycemic agent.