Anthracycline formulations

Abstract

The invention relates to reconstituted formulations comprising an anthracycline compound, ethanol, and water. The invention also relates to injectable compositions comprising the reconstituted formulation and Lactated Ringer's solution. Additionally, the invention relates to methods of using the formulations and compositions.

What is claimed is: 
     
         1 . A reconstituted formulation comprising an anthracycline compound, and a reconstitution liquid, wherein said reconstituted formulation is prepared by reconstituting a lyophilized composition of the anthracycline compound in a reconstitution liquid comprising ethanol and water. 
     
     
         2 . The reconstituted formulation of  claim 1 , wherein the anthracycline compound is DOXO-EMCH. 
     
     
         3 . The reconstituted formulation of  claim 1  or  2 , wherein the volume:volume ratio of ethanol:water is about 10:90 to about 90:10. 
     
     
         4 . The reconstituted formulation of  claim 3 , wherein the volume:volume ratio of ethanol:water is about 40:60 to about 60:40. 
     
     
         5 . The reconstituted formulation of  claim 4 , wherein the volume:volume ratio of ethanol:water is about 45:55 to about 55:45. 
     
     
         6 . The reconstituted formulation of  claim 5 , wherein the volume:volume ratio of ethanol:water is about 50:50. 
     
     
         7 . The reconstituted formulation of any one of  claims 1 - 6 , wherein the concentration of the anthracycline compound in the reconstituted formulation is from about 1 mg/ml to about 30 mg/ml. 
     
     
         8 . The reconstituted formulation of  claim 7 , wherein the concentration of the anthracycline compound in the reconstituted formulation is from about 5 mg/ml to about 25 mg/ml. 
     
     
         9 . The reconstituted formulation of  claim 8 , wherein the concentration of the anthracycline compound in the reconstituted formulation is about 10 mg/ml. 
     
     
         10 . An injectable composition of an anthracycline compound comprising the reconstituted formulation of any one of  claims 1 - 9  and Lactated Ringer's solution. 
     
     
         11 . The injectable composition of  claim 10 , wherein the anthracycline compound is DOXO-EMCH. 
     
     
         12 . The injectable composition of  claim 10 , wherein the concentration of the anthracycline compound in the injectable composition is from about 0.1 mg/ml to about 25 mg/ml. 
     
     
         13 . The injectable composition of  claim 10 , wherein the concentration of the anthracycline compound in the injectable composition is from about 7 mg/ml to about 17 mg/ml. 
     
     
         14 . The injectable composition of  claim 10 , wherein the concentration of the anthracycline compound in the injectable composition is from about 0.1 mg/ml to about 5 mg/ml. 
     
     
         15 . The injectable composition of  claim 14 , wherein the concentration of the anthracycline compound in the injectable composition is from about 0.25 mg/ml to about 4.5 mg/ml. 
     
     
         16 . The injectable composition of  claim 15 , wherein the concentration of the anthracycline compound in the injectable composition is about 2.4 mg/ml. 
     
     
         17 . The reconstituted formulation of any one of  claims 1 - 9 , or the injectable composition of any one of  claims 10 - 16 , for use in treating cancer in a patient. 
     
     
         18 . The reconstituted formulation or the injectable composition of  claim 17 , wherein the cancer is selected from: a solid tumor cancer, breast cancer, lung cancer, endometrial cancer, ovarian cancer, pancreatic cancer, cancer of the adrenal cortex, non-Hodgkin's lymphoma, multiple myeloma, leukemia, Kaposi's sarcoma, Ewing's sarcoma, soft tissue sarcoma, nephroblastoma, glioblastoma, prostate cancer, liver cancer, bone cancer, chondrosarcoma, renal cancer, bladder cancer, and gastric cancer. 
     
     
         19 . The reconstituted formulation or the injectable composition of  claim 18 , wherein the cancer is selected from: a solid tumor cancer and a soft tissue sarcoma. 
     
     
         20 . The reconstituted formulation or the injectable composition of  claim 18 , wherein the pancreatic cancer is pancreatic ductal adenocarcinoma. 
     
     
         21 . Use of the reconstituted formulation of any one of  claims 1 - 9 , or the injectable composition of any one of  claims 10 - 16 , in the manufacture of a medicament for treating cancer in a patient. 
     
     
         22 . The use according to  claim 21 , wherein the cancer is selected from: a solid tumor cancer, breast cancer, lung cancer, endometrial cancer, ovarian cancer, pancreatic cancer, cancer of the adrenal cortex, non-Hodgkin's lymphoma, multiple myeloma, leukemia, Kaposi's sarcoma, Ewing's sarcoma, soft tissue sarcoma, nephroblastoma, glioblastoma, prostate cancer, liver cancer, bone cancer, chondrosarcoma, renal cancer, bladder cancer, and gastric cancer. 
     
     
         23 . The use according to  claim 22 , wherein the cancer is selected from: a solid tumor cancer and a soft tissue sarcoma. 
     
     
         24 . The use according to  claim 22 , wherein the pancreatic cancer is pancreatic ductal adenocarcinoma. 
     
     
         25 . A method for treating cancer in a patient, comprising administering the reconstituted formulation of any one of  claims 1 - 9 , or the injectable composition of any one of  claims 10 - 16 , to a patient. 
     
     
         26 . The method of  claim 25 , wherein the reconstituted formulation or the injectable composition is administered intravenously. 
     
     
         27 . The method of any one of  claim 25  or  26 , wherein the cancer is selected from: a solid tumor cancer, breast cancer, lung cancer, endometrial cancer, ovarian cancer, pancreatic cancer, cancer of the adrenal cortex, non-Hodgkin's lymphoma, multiple myeloma, leukemia, Kaposi's sarcoma, Ewing's sarcoma, soft tissue sarcoma, nephroblastoma, glioblastoma, prostate cancer, liver cancer, bone cancer, chondrosarcoma, renal cancer, bladder cancer, and gastric cancer. 
     
     
         28 . The method according to  claim 27 , wherein the cancer is selected from: a solid tumor cancer and a soft tissue sarcoma. 
     
     
         29 . The method according to  claim 27 , wherein the pancreatic cancer is pancreatic ductal adenocarcinoma. 
     
     
         30 . A method of preparing a reconstituted formulation of an anthracycline compound, comprising reconstituting a lyophilized composition of the anthracycline compound in a reconstitution liquid comprising ethanol and water. 
     
     
         31 . The method of  claim 30 , wherein the anthracycline compound is DOXO-EMCH. 
     
     
         32 . The method of  claim 30  or  31 , wherein the volume:volume ratio of ethanol:water is about 10:90 to about 90:10. 
     
     
         33 . The method of  claim 32 , wherein the volume:volume ratio of ethanol:water is about 40:60 to about 60:40. 
     
     
         34 . The method of  claim 33 , wherein the volume:volume ratio of ethanol:water is about 45:55 to about 55:45. 
     
     
         35 . The method of  claim 34 , wherein the volume:volume ratio of ethanol:water is about 50:50. 
     
     
         36 . The method of any one of  claims 25 - 35 , wherein the concentration of the anthracycline compound in the reconstituted formulation is from about 1 mg/ml to about 30 mg/ml. 
     
     
         37 . The method of  claim 36 , wherein the concentration of the anthracycline compound in the reconstituted formulation is from about 5 mg/ml to about 25 mg/ml. 
     
     
         38 . The method of  claim 37 , wherein the concentration of the anthracycline compound in the reconstituted formulation is about 10 mg/ml. 
     
     
         39 . A method of preparing an injectable composition of an anthracycline compound comprising diluting the reconstituted formulation of any one of  claims 1 - 9  with Lactated Ringer's solution. 
     
     
         40 . The method of  claim 39 , wherein the anthracycline compound is DOXO-EMCH. 
     
     
         41 . The method of  claim 39  or  40 , wherein the concentration of the anthracycline compound in the injectable composition is from about 1 mg/ml to about 25 mg/ml. 
     
     
         42 . The method of  claim 41 , wherein the concentration of the anthracycline compound in the injectable composition is from about 1 mg/ml to about 5 mg/ml. 
     
     
         43 . The method of  claim 42 , wherein the concentration of the anthracycline compound in the injectable composition is from about 7 mg/ml to about 17 mg/ml.