Injectable ready-to-use solutions containing an antitumor anthracycline glycoside

Abstract

A sealed glass container containing therein a stable, injectable, sterile, pyrogen-free doxorubicin anti-tumor composition in a solution which consists essentially of a physiologically acceptable salt of doxorubicin dissolved in a physiologically acceptable solvent therefor, wherein said solution has not been reconstituted from a lyophilizate, and wherein said solution has a pH of from 2.5-3.5 and a concentration of said doxorubicin of from 0.1 to 100 mg/ml.

What is claimed as new and desired to be secured by Letters of patent of the United States is:  
     
         1 - 17 . (Cancelled)  
     
     
         18 . A physiologically acceptable solution of doxorubicin hydrochloride dissolved in a physiologically acceptable solvent, having a pH adjusted to from about 2.5 to 5.0 with a physiologically acceptable acid and has a concentration of doxorubicin of from 0.1 to 100 mg/ml.  
     
     
         19 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18 , wherein said solution has not been reconstituted from a lyophilizate.  
     
     
         20 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18 , wherein said solution is contained in a sealed container.  
     
     
         21 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18 , wherein said solution has not been reconstituted from a lyophilizate and is contained in a sealed container.  
     
     
         22 . A physiologically acceptable solution of doxorubicin hydrochloride dissolved in a physiologically acceptable solvent, having a pH adjusted to from 2.5 to 5.0 with a physiologically acceptable acid selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, acetic acid, succinic acid, tartaric acid, ascorbic acid, citric acid, glutamic acid, benzoic acid, methane sulfonic acid, and ethane sulfonic acid and the concentration of said doxorubicin hydrochloride being from 0.1 to 100 mg/ml.  
     
     
         23 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 22 , wherein said solution has not been reconstituted from a lyophilizate.  
     
     
         24 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 22 , wherein said solution is contained in a sealed container.  
     
     
         25 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 22 , wherein said solution has not been reconstituted from a lyophilizate and is contained in a sealed container.  
     
     
         26 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18  or  22 , wherein the physiologically acceptable solvent is selected from the group consisting of water, physiological saline, dextrose, polyethylene glycol, N,N-dimethylacetamide, N-hydroxy-2-ethyl-lactamide, ethanol, benzyl alcohol, propylene glycol, glycerin, diacetine, triacetine, polyethylene glycol 400, propylene glycol methylether, isopropylidenglycerin, dimethylisosorbide, 2-pyrrolidone, N-methyl-2-pyrrolidone, Brij®, Cremophor®, Myrj®, Tween® and Pluronics® and mixtures thereof.  
     
     
         27 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18  or  22 , wherein the physiologically acceptable solvent is water.  
     
     
         28 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18  or  22 , wherein said physiologically acceptable solvent is a saline solution.  
     
     
         29 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18  or  22 , wherein said physiologically acceptable solvent is a dextrose solution.  
     
     
         30 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18  or  22 , wherein said physiologically acceptable solvent is sterile water.  
     
     
         31 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18  or  22 , further comprising a tonicity adjusting agent.  
     
     
         32 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18  or  22 , wherein the concentration of doxorubicin hydrochloride is from 0.1 to 50 mg/ml.  
     
     
         33 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18  or  22 , wherein the concentration of doxorubicin hydrochloride is from 1 to 20 mg/ml.  
     
     
         34 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18  or  22 , wherein the pH of said solution is from about 2.5 to about 3.5.  
     
     
         35 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18  or  22 , wherein the pH of said solution is from about 2.7 to about 3.3.  
     
     
         36 . The physiologically acceptable solution of doxorubicin hydrochloride of  claim 18  or  22 , wherein said solution is storage stable, intravenously injectable, sterile and pyrogen-free.  
     
     
         37 . A physiologically acceptable solution of anthracycline glycoside selected from the group consisting of doxorubicin hydrochloride, epirubicin hydrochloride and idarubicin hydrochloride dissolved in a physiologically acceptable solvent, having a pH adjusted to from about 2.5 to 5.0 with a physiologically acceptable acid and has a concentration of idarubicin of from 0.1 to 100 mg/ml.  
     
     
         38 . The physiologically acceptable solution of anthracycline glycoside of  claim 37 , wherein said solution has not been reconstituted from a lyophilizate.  
     
     
         39 . The physiologically acceptable solution of anthracycline glycoside of  claim 37 , wherein said solution is contained in a sealed container.  
     
     
         40 . The physiologically acceptable solution of anthracycline glycoside of  claim 37 , wherein said solution has not been reconstituted from a lyophilizate and is contained in a sealed container.  
     
     
         41 . A physiologically acceptable solution of anthracycline glycoside selected from the group consisting of doxorubicin hydrochloride, epirubicin hydrochloride and idarubicin hydrochloride dissolved in a physiologically acceptable solvent, having a pH adjusted to from 2.5 to 5.0 with a physiologically acceptable acid selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, acetic acid, succinic acid, tartaric acid, ascorbic acid, citric acid, glutamic acid, benzoic acid, methane sulfonic acid, and ethane sulfonic acid and the concentration of said idarubicin hydrochloride being from 0.1 to 100 mg/ml.  
     
     
         42 . The physiologically acceptable solution of anthracycline glycoside of  claim 41 , wherein said solution has not been reconstituted from a lyophilizate.  
     
     
         43 . The physiologically acceptable solution of anthracycline glycoside of  claim 41 , wherein said solution is contained in a sealed container.  
     
     
         44 . The physiologically acceptable solution of anthracycline glycoside of  claim 41 , wherein said solution has not been reconstituted from a lyophilizate and is contained in a sealed container.  
     
     
         45 . The physiologically acceptable solution of anthracycline glycoside of  claim 37  or  41  wherein the physiologically acceptable solvent is selected from the group consisting of water, physiological saline, dextrose, polyethylene glycol, N,N-dimethylacetamide, N-hydroxy-2-ethyl-lactamide, ethanol, benzyl alcohol, propylene glycol, glycerin, diacetine, triacetine, polyethylene glycol 400, propylene glycol methylether, isopropylidenglycerin, dimethylisosorbide, 2-pyrrolidone, N-methyl-2-pyrrolidone, Brij®, Cremophor®, Myrj®, Tween® and Pluronics® and mixtures thereof.  
     
     
         46 . The physiologically acceptable solution of anthracycline glycoside of  claim 37  or  41  wherein the physiologically acceptable solvent is water.  
     
     
         47 . The physiologically acceptable solution of anthracycline glycoside of  claim 37  or  41  wherein said physiologically acceptable solvent is a saline solution.  
     
     
         48 . The physiologically acceptable solution of anthracycline glycoside of  claim 37  or  41  wherein said physiologically acceptable solvent is a dextrose solution.  
     
     
         49 . The physiologically acceptable solution of anthracycline glycoside of  claim 37  or  41  wherein said physiologically acceptable solvent is sterile water.  
     
     
         50 . The physiologically acceptable solution of anthracycline glycoside of  claim 37  or  41  further comprising a tonicity adjusting agent.  
     
     
         51 . The physiologically acceptable solution of anthracycline glycoside of  claim 37  or  41  wherein the concentration of anthracycline glycoside selected from the group consisting of doxorubicin hydrochloride, epirubicin hydrochloride and idarubicin hydrochloride is from 0.1 to 50 mg/ml.  
     
     
         52 . The physiologically acceptable solution of anthracycline glycoside of  claim 37  or  41  wherein the concentration of anthracycline glycoside selected from the group consisting of doxorubicin hydrochloride, epirubicin hydrochloride and idarubicin hydrochloride is from 1 to 20 mg/ml.  
     
     
         53 . The physiologically acceptable solution of anthracycline glycoside of  claim 37  or  41  wherein the pH of said solution is from about 2.5 to about 3.5.  
     
     
         54 . The physiologically acceptable solution of anthracycline glycoside of  claim 37  or  41  wherein the pH of said solution is from about 2.7 to about 3.3.  
     
     
         55 . The physiologically acceptable solution of anthracycline glycoside of  claim 37  or  41  wherein said solution is storage stable, intravenously injectable, sterile and pyrogen-free.