Claims for Patent: 7,005,421

Summary for Patent: 7,005,421

Title:	Injectable ready-to-use solutions containing an antitumor anthracycline glycoside
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.
Inventor(s):	Gatti; Gaetano (Sesto San Giovanni, IT), Oldani; Diego (Robecco sul Naviglio, IT), Bottoni; Giuseppe (Bergamo, IT), Confalonieri; Carlo (Cusano Milanino, IT), Gambini; Luciano (Cornaredo, IT), De Ponti; Roberto (Milan, IT)
Assignee:	Pharmacia & Upjohn Company (Kalamazoo, MI)
Application Number:	10/454,275
Patent Claims:	1. A physiologically acceptable solution of doxorubicin hydrochloride dissolved in a physiologically acceptable solvent, having a pH adjusted to from 2.5 to 3.5 with a physiologically acceptable acid selected from the group consisting of hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, and tartaric acid, the concentration of said doxorubicin hydrochloride being from 0.1 to 100 mg/ml, wherein said solution is in a sealed container. 2. 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 3.5 with a physiologically acceptable acid selected from the group consisting of hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, tartaric acid, acetic acid, succinic acid, ascorbic acid, citric acid, and glutamic acid and the concentration of said anthracycline glycoside being from 0.1 to 100 mg/ml. 3. The solution of claim 2, wherein the physiologically acceptable solvent is selected from the group consisting of water, ethanol, polyethylene glycol, dimethyl acetamide, and mixtures thereof. 4. The solution of claim 2, wherein the physiologically acceptable solvent is water. 5. The solution of claim 2, further comprising a tonicity adjusting agent. 6. The solution of claim 2, 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. 7. The solution of claim 2, 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. 8. The solution of claim 2, wherein the pH of said solution is from about 2.7 to about 3.3. 9. The solution of claim 2, wherein said physiologically acceptable solvent is a saline solution. 10. The solution of claim 2, wherein said physiologically acceptable solvent is a dextrose solution. 11. The solution of claim 2, wherein said physiologically acceptable solvent is sterile water. 12. A physiologically acceptable aqueous 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 3.5 with a physiologically acceptable acid and the concentration of said anthracycline glycoside being from 0.1 to 100 mg/ml. 13. 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 3.5 with a physiologically acceptable acid selected from the group consisting of hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, tartaric acid, and acetic acid and the concentration of said anthracycline glycoside being from 0.1 to 100 mg/ml. 14. A storage stable physiologically acceptable aqueous solution of idarubicin hydrochloride dissolved in a physiologically acceptable solvent, having a pH adjusted to from about 2.7 to about 3.5 with a physiologically acceptable acid and the concentration of said idarubicin hydrochloride being from 0.1 to 100 mg/ml. 15. A storage stable 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 2.7 to 3.3 with a physiologically acceptable acid selected from the group consisting of hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, tartaric acid and acetic acid and the concentration of said anthracycline glycoside being from 0.1 to 100 mg/ml. 16. 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 aqueous solvent, having a pH adjusted to from 2.5 to 3.5 with a physiologically acceptable acid selected from the group consisting of hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, tartaric acid, acetic acid, succinic acid, ascorbic acid, citric acid, and glutamic acid and the concentration of said anthracycline glycoside being from 0.1 to 100 mg/ml. 17. The solution of claim 16, further comprising a tonicity adjusting agent. 18. The solution of claim 16, 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. 19. The solution of claim 16, 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. 20. The solution of claim 16, wherein the pH of said solution is from about 2.7 to about 3.3. 21. The solution of claim 16, wherein said physiologically acceptable solvent is a saline solution. 22. The solution of claim 16, wherein said physiologically acceptable solvent is a dextrose solution. 23. The solution of claim 16, wherein said physiologically acceptable solvent is sterile water. 24. 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 3.5 with a physiologically acceptable acid selected from the group consisting of hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, and tartaric acid, the concentration of said anthracycline glycoside being from 0.1 to 100 mg/ml, wherein said solution is in a sealed container. 25. The solution of claim 12, wherein the pH of said solution is from about 2.7 to about 3.3. 26. The solution of claim 13, wherein the pH of said solution is from about 2.7 to about 3.3. 27. The solution of claim 24, wherein the pH of said solution is from about 2.7 to about 3.3. 28. The solution of claim 12, 13, or 24, wherein said physiologically acceptable solvent is a saline solution. 29. The solution of claim 12, 13, or 24, wherein said physiologically acceptable solvent is a dextrose solution. 30. The solution of claim 12, 13, or 24, wherein said physiologically acceptable solvent is sterile water. 31. The solution of claim 2, 12, 13, or 16, wherein said solution is contained in a sealed container. 32. The solution of claim 2, 12, 13, 16, or 24, wherein said physiologically acceptable solvent is selected from the group consisting of water, physiological saline, aliphatic amides, alcohols, glycols and polyalcohols, esters of polyalcohols, polyglycols and polyethers, dioxolanes, dimethylisosorbide, pyrrolidone derivatives, polyoxyethylenated fatty alcohols, esters of polyoxyethylenated fatty alcohols, polysorbates, and polyoxyethylene derivatives of polypropyleneglycols. 33. The solution of claim 2, 12, 13, 16, or 24, further comprising a co-solubilizing agent selected from the group consisting of water, physiological saline, aliphatic amides, alcohols, glycols and polyalcohols, esters of polyalcohols, polyglycols and polyethers, dioxolanes, dimethylisosorbide, pyrrolidone derivatives, polyoxyethylenated fatty alcohols, esters of polyoxyethylenated fatty alcohols, polysorbates, and polyoxyethylene derivatives of polypropyleneglycols. 34. The solution of claim 33, wherein the aliphatic amide is selected from the group consisting of N,N-dimethylacetamide and N-hydroxy-2-ethyl-lactamide. 35. The solution of claim 33, wherein the alcohol is selected from the group consisting of ethanol and benzyl alcohol. 36. The solution of claim 33, wherein the glycols and polyalcohols are selected from the group consisting of propyleneglycol and glycerin. 37. The solution of claim 33, wherein the ester of polyalcohols is selected from the group consisting of diacetine and triacetine. 38. The solution of claim 33, wherein the ester polyglycols and polyethers are selected from the group consisting of polyethyleneglycol 400 and propyleneglycol methylesters. 39. The solution of claim 33, wherein the dioxolane is isopropylidenglycerin. 40. The solution of claim 33, wherein the pyrrolidone derivative is selected from the group consisting of 2-pyrrolidone, N-methyl-2-pyrrolidone and polyvinylpyrrolidone. 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 aqueous solvent, having a pH adjusted to from 2.5 to 3.5 with a physiologically acceptable acid selected from the group consisting of hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, tartaric acid, acetic acid, succinic acid, ascorbic acid, citric acid, and glutamic acid and the concentration of said anthracycline glycoside being from 0.1 to 100 mg/ml, wherein said solution is in a sealed container. 42. The solution of claim 41, wherein said physiologically acceptable solvent is selected from the group consisting of water, physiological saline, aliphatic amides, alcohols, glycols and polyalcohols, esters of polyalcohols, polyglycols and polyethers, dioxolanes, dimethylisosorbide, pyrrolidone derivatives, polyoxyethylenated fatty alcohols, esters of polyoxyethylenated fatty alcohols, polysorbates, and polyoxyethylene derivatives of polypropyleneglycols. 43. The solution of claim 41, wherein the physiologically acceptable solvent is water. 44. The solution of claim 41, further comprising a co-solubilizing agent selected from the group consisting of water, physiological saline, aliphatic amides, alcohols, glycols and polyalcohols, esters of polyalcohols, polyglycols and polyethers, dioxolanes, dimethylisosorbide, pyrrolidone derivatives, polyoxyethylenated fatty alcohols, esters of polyoxyethylenated fatty alcohols, polysorbates, and polyoxyethylene derivatives of polypropyleneglycols. 45. The solution of claim 44, wherein the aliphatic amide is selected from the group consisting of N,N-dimethylacetamide and N-hydroxy-2-ethyl-lactamide. 46. The solution of claim 44, wherein the alcohol is selected from the group consisting of ethanol and benzyl alcohol. 47. The solution of claim 44, wherein the glycols and polyalcohols are selected from the group consisting of propyleneglycol and glycerin. 48. The solution of claim 44, wherein the ester of polyalcohols is selected from the group consisting of diacetine and triacetine. 49. The solution of claim 44, wherein the polyglycols and polyethers are selected from the group consisting of polyethyleneglycol 400 and propyleneglycol methylesters. 50. The solution of claim 44, wherein the dioxolane is isopropylidenglycerin. 51. The solution of claim 44, wherein the pyrrolidone derivative is selected from the group consisting of 2-pyrrolidone, N-methyl-2-pyrrolidone and polyvinylpyrrolidone. 52. The solution of claim 41, wherein the anthracycline glycoside is idarubicin hydrochloride. 53. The solution of claim 52, wherein said physiologically acceptable solvent is selected from the group consisting of water, physiological saline, aliphatic amides, alcohols, glycols and polyalcohols, esters of polyalcohols, polyglycols and polyethers, dioxolanes, dimethylisosorbide, pyrrolidone derivatives, polyoxyethylenated fatty alcohols, esters of polyoxyethylenated fatty alcohols, polysorbates, and polyoxyethylene derivatives of polypropyleneglycols. 54. The solution of claim 52, wherein the physiologically acceptable solvent is water. 55. The solution of claim 52, further comprising a co-solubilizing agent selected from the group consisting of water, physiological saline, aliphatic amides, alcohols, glycols and polyalcohols, esters of polyalcohols, polyglycols and polyethers, dioxolanes, dimethylisosorbide, pyrrolidone derivatives, polyoxyethylenated fatty alcohols, esters of polyoxyethylenated fatty alcohols, polysorbates, and polyoxyethylene derivatives of polypropyleneglycols. 56. The solution of claim 55, wherein the glycols and polyalcohols are selected from the group consisting of propyleneglycol and glycerin. 57. The solution of claim 41, wherein the pH is adjusted to about 3.5. 58. The solution of claim 41, wherein the physiologically acceptable acid is hydrochloric acid.

Details for Patent 7,005,421

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2005-08-02