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

• US 6,107,285 A
• Filed: 01/29/1992
• Issued: 08/22/2000
• Est. Priority Date: 08/02/1985
• Status: Expired due to Fees

• Current Assignee: Pharmacia & Upjohn Company (Pfizer Inc.)
• Original Assignee: Pharmacia & Upjohn Company (Pfizer Inc.)
• Inventors: Bottoni, Giuseppe, Gambini, Luciano, De Ponti, Roberto, Oldani, Diego, Gatti, Gaetano, Confalonieri, Carlo
• Primary Examiner(s): Peselev, Elli
• Application Number:
  US07/827,742
• Time in Patent Office: 3,128 Days
• Field of Search: 536/6.4, 536/34, 424/78, 514/34
• US Class Current: 514/34
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: C07H 15/252 Naphthacene radicals, e.g. daunomycins, adriamycins

Abstract

According to the invention there is provided a sterile, pyrogen-free, ready-to-use solution of an anthracycline glycoside, especially doxorubicin, which consists essentially of a physiologically acceptable salt of an anthracycline glycoside dissolved in a physiologically acceptable solvent therefor, which has not been reconstituted from a lyophilizate and which has a pH of from 2.5 to 6.5. The solution of the invention is particularly advantageous for the administration by injection of the anthracycline glycoside drugs, e.g. doxorubicin, in the treatment of both human and animal tumors.

Claims

1. A physiologically acceptable solution of anthracycline glycoside selected from the group consisting of idarubicin hydrochloride, doxorubicin hydrochloride and epirubicin hydrochloride dissolved in a physiologically acceptable aqueous 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, sulfuric acid, phosphoric acid, methane sulfonic acid, and tartaric acid, the concentration of said anthracycline glycoside being from 0.1 to 100 mg/ml, wherein said solution is contained in a sealed container.

2. The solution of claim 1 wherein said physiologically acceptable aqueous solvent is selected from the group consisting of water, ethanol, polyethylene glycol, dimethylacetamide, and mixtures thereof.

3. The solution of claim 1 wherein the physiologically acceptable aqueous solvent is water.

4. The solution of claim 1 wherein the concentration of the doxorubicin is from 0.1 to 50 mg/ml.

5. The solution of claim 4 wherein the concentration of doxorubicin is from 1 to 20 mg/ml.

6. The solution of claim 1 wherein the concentration of doxorubicin is about 2 mg/ml.

7. The solution of claim 1 wherein the concentration of doxorubicin is about 5 mg/ml.

9. The anthracycline glycoside solution of claim 1, wherein said solution exhibits storage stability as a result of said pH being adjusted to the said pH range using said acids.

11. The solution of claim 1 wherein the concentration of anthracycline glycoside is about 1 mg/ml.

12. The solution of claim 11 wherein the physiologically acceptable acid is hydrochloric acid.

13. The solution of claim 12 wherein the anthracycline glycoside is idarubicin hydrochloride.

8. A sealed container containing a stable, intravenously injectable, sterile, pyrogen-free doxorubicin solution which consists essentially of doxorubicin hydrochloride dissolved in a physiologically acceptable solvent therefore, wherein said solution has a pH adjusted to 2.71 to 3.14 with a physiologically acceptable acid and has a concentration of doxorubicin of from 0.1 to 100 mg/ml.

10. The container of claim 8, wherein said doxorubicin solution exhibits storage stability as a result of said pH being adjusted to the said pH range using said acids.