Patent EA-003936-B1 (EA)
Title: Formulations for parenteral use of estramustine phosphate and sulfoalkyl ether cyclodextrins
Inventor: MUGGETTI LORENA
IPC: A61K9/127
Filed: 2000-08-03
Abstract: 1. A pharmaceutical formulation which comprises a parenterally acceptable carrier or diluent and estramustine phosphate and a sulfoalkyl ether cyclodextrin. 2. A formulation according to claim 1 wherein the weight ratio of estramustine phosphate to the sulfoalkyl ether cyclodextrin is from about 1: 1 to about 1: 5. 3. A formulation according to claim 1 or 2 which is in single infusion dosage form comprising at least 1300 mg of the estramustine phosphate. 4. A formulation according to any one of the preceding claims which is in single infusion dosage form comprising at least 950mg/m<2> of the estramustine phosphate. 5. A formulation according to any one of the preceding claims wherein the sulfoalkyl ether cyclodextrin is a straight or branched C1-C6 sulfoalkyl ether cyclodextrin. 6. A formulation according to claim 5 wherein the sulfoalkyl ether cyclodextrin is sulfobutyl ether beta-cyclodextrin. 7. A formulation according to any one of the preceding claims for intravenous use. 8. A formulation according to any one of the preceding claims wherein the estramustine phosphate is in the form of a pharmaceutically acceptable salt for intravenous use. 9. A formulation according to claim 8 wherein the estramustine phosphate is in the form of N-methyl glucamine salt. 10. A formulation according to any one of the preceding claim for use in the treatment of cancer. 11. A formulation as claimed in claim 10 wherein the cancer is prostate cancer, breast cancer, melanoma, lung cancer, pancreatic cancer, colorectal cancer, ovarian cancers or cancer of the brain. 12. A formulation according to claim 1 wherein the parenterally acceptable carrier is a physiological solution for parenteral use which contains the sulfoalkyl ether cyclodextrin, and the estramustine phosphate is in lyophilised form. 13. A formulation according to claim 1 wherein the estramustine phosphate is in admixture with the sulfoalkyl ether cyclodextrin. 14. A product which comprises (i) a pharmaceutical formulation which comprises a parenterally acceptable carrier or diluent, estramustine phosphate and a sulfoalkyl ether cyclodextrin, and (ii) one or more chemotherapeutic agents; as a combined preparation for simultaneous, separate or sequential use in anticancer therapy. 15. A product according to claim 14 wherein the sulfoalkyl ether cyclodextrin is sulfobutyl ether beta-cyclodextrin. 16. A product according to claim 14 or 15 wherein the chemotherapeutic agent, optionally encapsulated within liposomes, is selected from taxane, taxane derivatives, CPT-11, camptothecin and derivatives thereof, doxorubicin, idarubicin or epirubicin, etoposide, navelbine, vinblastine, carboplatin, cisplatin, Sugen SU 6668 and Sugen SU 5416. 17. A product according to claim 14 for intravenous use. 18. A product according to claim 14 for use in the treatment of prostate cancer, breast cancer, melanoma, lung cancer, pancreatic cancer, colorectal cancer, ovarian cancer or cancer of the brain. 19. A formulation as defined in claim 7 for use in suppressing or reducing the side-effects associated with the intravenous administration of estramustine phosphate and pharmaceutically acceptable salts thereof. 20. A formulation according to claim 19 wherein the side effects comprise ulcerative lesions and thrombophlebitis at the site of injection. 21. A product which comprises estramustine phosphate in lyophilised form and a physiological solution for parenteral use containing a sulfoalkyl ether cyclodextrin. 22. Use, in the manufacture of a medicament for parenteral administration, of estramustine phosphate and a sulfoalkyl ether cyclodextrin. 23. Use according to claim 22 wherein the medicament is for intravenous administration.