Pharmaceutical composition useful for treating chronic myeloid leukemia

Abstract

The present invention relates to a pharmaceutical composition useful for treating chronic myeloid leukemia where Bcr-Abl kinase is constitutively expressed in animals and humans, said composition comprising an effective amount of analogs of chlorogenic acid such as neochlorogenic acid (5-O-caffeoyl quinic acid), cryptochlorogenic acid (4-O-Caffeoyl quinic acid), 3-O-(3′-methylcaffeoyl) quinic acid and 5-O-(Caffeoyl-4′-methyl) quinic acid and/or its salts such as sodium, potassium and ammonium together with pharmaceutically acceptable additives.

1 . A pharmaceutical composition useful for treating chronic myeloid leukemia where Bcr-Abl kinase is constitutively expressed in animals and humans, said composition comprising an effective amount of analogs of chlorogenic acid and/or its salts along with pharmaceutically acceptable additives.  
     
     
         2 . A composition as claimed in  claim 1 , wherein said composition is also useful for diseases caused by over expression of Abl type of kinase  
     
     
         3 . The composition as claimed in  claim 1 , wherein the analogs of chlorogenic is selected from a group consisting of neochlorogenic acid (5-O-caffeoyl quinic acid), cryptochlorogenic acid (4-O-Caffeoyl quinic acid), 3-O-(3′-methylcaffeoyl) quinic acid and 5-O-(Caffeoyl-4′-methyl) quinic acid.  
     
     
         4 . The composition as claimed in  claim 1 , wherein the analogs of chlorogenic acid are obtained either from natural sources or synthetically prepared.  
     
     
         5 . The composition as claimed in  claim 1 , wherein the salt of chlorogenic acid analog is selected from sodium, potassium and ammonium.  
     
     
         6 . The composition as claimed in  claim 1  wherein, the additive is selected from a group consisting of nutrients such as proteins, carbohydrates, sugars, talc, magnesium stearate, cellulose, calcium carbonate, starch-gelatin paste and/or pharmaceutically acceptable carriers, excipient, diluents or solvents.  
     
     
         7 . The composition as claimed in  claim 1  is administered through oral, intravenous, intramuscular or subcutaneous routes.  
     
     
         8 . The composition as claimed in  claim 1  is administered at a dose level ranging between 1 and 20 mg per kg body weight/day.  
     
     
         9 . The composition as claimed in  claim 1 , which is administered for at least four weeks and up to twelve weeks.  
     
     
         10 . The composition as claimed in  claim 1 , wherein said composition is also useful for relapsed conditions of CML.  
     
     
         11 . The composition as claimed in  claim 1  wherein, the said composition inhibits the growth of leukemic cell types K562 and Molt-4.  
     
     
         12 . The composition as claimed in  claim 1  IC 50  value for in vitro activity against K562 cells of concentration of 10 4 /well is up to 27.0 nanomole/ml.  
     
     
         13 . Use of pharmaceutical composition as claimed in  claim 1  for the treatment of chronic myeloid leukemia in a subject where Bcr-Abl kinase is constitutively expressed in animals and humans, said composition comprising an effective amount of analogs of chlorogenic acid and/or its salts along with pharmaceutically acceptable additives.  
     
     
         14 . A use as claimed in  claim 13  wherein the subject is selected from a mammal preferably a human being.  
     
     
         15 . A use as claimed in  claim 13 , wherein said composition is also useful for diseases caused by over expression of Abl type of kinase.  
     
     
         16 . A use as claimed in  claim 13 , wherein the analogs of chlorogenic is selected from a group consisting of neochlorogenic acid (5-O-caffeoyl quinic acid), cryptochlorogenic acid (4-O-Caffeoyl quinic acid), 3-O-(3′-methylcaffeoyl) quinic acid and 5-O-(Caffeoyl-4′-methyl) quinic acid.  
     
     
         17 . A use as claimed in  claim 13 , wherein the analogs of chlorogenic acid are obtained either from natural sources or synthetically prepared.  
     
     
         18 . A use as claimed in  claim 13 , wherein the salt of chlorogenic acid analog is selected from sodium, potassium and ammonium.  
     
     
         19 . A use as claimed in  claim 13  wherein, the additive is selected from a group consisting of nutrients such as proteins, carbohydrates, sugars, talc, magnesium stearate, cellulose, calcium carbonate, starch-gelatin paste and/or pharmaceutically acceptable carriers, excipient, diluents or solvents.  
     
     
         20 . A use as claimed in  claim 13 , wherein said composition is administered through oral, intravenous, intramuscular or subcutaneous routes.  
     
     
         21 . A use as claimed in  claim 13  wherein the said composition is administered at a dose level ranging between 1 and 20 mg per kg body weight/day.  
     
     
         22 . A use as claimed in  claim 13  wherein the said composition is administered for at least four weeks and up to twelve weeks.  
     
     
         23 . A use as claimed in  claim 13  wherein said composition is also useful for relapsed conditions of CML.  
     
     
         24 . A use as claimed in  claim 13  wherein, the said composition inhibits the growth of leukemic cell types K562 and Molt-4.  
     
     
         25 . A use as claimed in  claim 13  wherein IC 50  value of the composition for in vitro activity against K562 cells of concentration of 10 4 /well is up to 27.0 nanomole/ml.  
     
     
         26 . A method of treating chronic myeloid leukemia CML where Bcr-Abl kinase is constitutively expressed in animals and humans, said method comprising administering a pharmaceutical composition comprising an effective amount of analogs of chlorogenic acid and/or its salts along with pharmaceutically acceptable additives.  
     
     
         27 . A method as claimed in  claim 26 , wherein the said composition is also useful for diseases caused by over expression of Abl type of kinase.  
     
     
         28 . The method as claimed in  claim 26 , wherein the analogs of chlorogenic is selected from a group consisting of neochlorogenic acid (5-O-caffeoyl quinic acid), cryptochlorogenic acid (4-O-Caffeoyl quinic acid), 3-O-(3′-methylcaffeoyl) quinic acid and 5-O-(Caffeoyl-4′-methyl) quinic acid.  
     
     
         29 . The method as claimed in  claim 26 , wherein the analogs of chlorogenic acid are obtained either from natural sources or synthetically prepared.  
     
     
         30 . The method as claimed in  claim 26 , wherein the salt of chlorogenic acid analog is selected from sodium, potassium and ammonium.  
     
     
         31 . The method as claimed in  claim 26 , wherein, the additive is selected from a group consisting of nutrients such as proteins, carbohydrates, sugars, talc, magnesium stearate, cellulose, calcium carbonate, starch-gelatin paste and/or pharmaceutically acceptable carriers, excipient, diluents or solvents.  
     
     
         32 . The method as claimed in  claim 26 , wherein the said composition is administered through oral, intravenous, intramuscular or subcutaneous routes.  
     
     
         33 . The method as claimed in  claim 26 , wherein the said composition is administered at a dose level ranging between 1 and 20 mg per kg body weight/day.  
     
     
         34 . The method as claimed in  claim 26 , wherein the said composition is administered for at least four weeks and up to twelve weeks.  
     
     
         35 . The method as claimed in  claim 26 , wherein the said composition is also useful for relapsed conditions of CML.  
     
     
         36 . The method as claimed in  claim 26  wherein, the said composition inhibits the growth of leukemic cell types K562 and Molt-4.  
     
     
         37 . The method as claimed in  claim 26 , wherein IC 50  value of the composition for in vitro activity against K562 cells of concentration of 10 4 /well is up to 27.0 nanomole/ml.