Claims
- 1. A pharmaceutical formulation comprising at least one antineoplastic agent or a pharmaceutically acceptable salt thereof, at least one aqueous diluent, and at least one dissolution enhancing agent sufficient to substantially dissolve said antineoplastic agent, wherein said dissolution enhancing agent is urea, L-histidine, L-threonine, L-asparagine, L-serine, L-glutamine or mixtures thereof.
- 2. The pharmaceutical formulation according to claim 1, wherein said antineoplastic agent is Temozolomide, Uracil Mustard, Chlormethine, Cyclophosphamide, Ifosfamide, Melphalan, Chlorambucil, Pipobroman, Triethylenemelamine, Triethylenethiophosphoramine, Busulfan, Carmustine, Lomustine, Streptozocin, Dacarbazine, Methotrexate, 5-Fluorouracil, Floxuridine, Cytarabine, 6-Mercaptopurine, 6-Thioguanine, Fludarabine phosphate, Pentostatine, Gemcitabine, Vinblastine, Vincristine, Vindesine, Bleomycin, Dactinomycin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Paclitaxel, Mithramycin, Deoxycoformycin, Mitomycin-C, L-Asparaginase, Interferons, Etoposide, Teniposide 17.alpha.-Ethinylestradiol, Diethylstilbestrol, Testosterone, Prednisone, Fluoxymesterone, Dromostanolone propionate, Testolactone, Megestrolacetate, Tamoxifen, Methylprednisolone, Methyltestosterone, Prednisolone, Triamcinolone, Chlorotrianisene, Hydroxyprogesterone, Aminoglutethimide, Estramustine, Medroxyprogesteroneacetate, Leuprolide, Flutamide, Toremifene, Goserelin, Cisplatin, Carboplatin, Hydroxyurea, Amsacrine, Procarbazine, Mitotane, Mitoxantrone, Levamisole, Navelbene, Anastrazole, Letrazole, Capecitabine, Reloxafine, Droloxafine, Hexamethylmelamine or mixtures thereof.
- 3. The pharmaceutical formulation according to claim 2, wherein said antineoplastic agent is Temozolomide.
- 4. The pharmaceutical formulation according to claim 1, further comprising an excipient selected from polysorbate, polyethylene glycol, propylene glycol, polypropylene glycol, or mixtures thereof.
- 5. The pharmaceutical formulation according to claim 4, wherein said excipient is polysorbate 20, polysorbate 80, or mixtures thereof.
- 6. The pharmaceutical formulation according to claim 1, further comprising at least one bulking agent.
- 7. The pharmaceutical formulation according to claim 6, wherein said bulking agent is mannitol, lactose, sucrose, sodium chloride, trehalose, dextrose, starch, hetastarch, cellulose, cyclodextrins, glycine, or mixtures thereof.
- 8. The pharmaceutical formulation according to claim 7, wherein said bulking agent is mannitol.
- 9. The pharmaceutical formulation according to claim 1, further comprising at least one buffer.
- 10. The pharmaceutical formulation according to claim 9, wherein said buffer is lithium citrate monohydrate, sodium citrate monohydrate, potassium citrate monohydrate, calcium citrate monohydrate, lithium citrate dihydrate, sodium citrate dihydrate, potassium citrate dihydrate, calcium citrate dihydrate, lithium citrate trihydrate, sodium citrate trihydrate, potassium citrate trihydrate, calcium citrate trihydrate, lithium citrate tetrahydrate, sodium citrate tetrahydrate, potassium citrate tetrahydrate, calcium citrate tetrahydrate, lithium citrate pentahydrate, sodium citrate pentahydrate, potassium citrate pentahydrate, calcium citrate pentahydrate, lithium citrate hexahydrate, sodium citrate hexahydrate, potassium citrate hexahydrate, calcium citrate hexahydrate, lithium citrate heptahydrate, sodium citrate heptahydrate, potassium citrate heptahydrate, calcium citrate heptahydrate, lithium lactate, sodium lactate, potassium lactate, calcium lactate, lithium phosphate, sodium phosphate, potassium phosphate, calcium phosphate, lithium maleate, sodium maleate, potassium maleate, calcium maleate, lithium tartarate, sodium tartarate, potassium tartarate, calcium tartarate, lithium succinate, sodium succinate, potassium succinate, calcium succinate, lithium acetate, sodium acetate, potassium acetate, calcium acetate, or mixtures thereof.
- 11. The pharmaceutical formulation according to claim 10, wherein said buffer is lithium citrate monohydrate, sodium citrate monohydrate, potassium citrate monohydrate, calcium citrate monohydrate, lithium citrate dihydrate, sodium citrate dihydrate, potassium citrate dihydrate, calcium citrate dihydrate, lithium citrate trihydrate, sodium citrate trihydrate, potassium citrate trihydrate, calcium citrate trihydrate, lithium citrate tetrahydrate, sodium citrate tetrahydrate, potassium citrate tetrahydrate, calcium citrate tetrahydrate, lithium citrate pentahydrate, sodium citrate pentahydrate, potassium citrate pentahydrate, calcium citrate pentahydrate, lithium citrate hexahydrate, sodium citrate hexahydrate, potassium citrate hexahydrate, calcium citrate hexahydrate, lithium citrate heptahydrate, sodium citrate heptahydrate, potassium citrate heptahydrate, calcium citrate heptahydrate or mixtures thereof.
- 12. The pharmaceutical formulation according to claim 1, further comprising a pH adjuster.
- 13. The pharmaceutical formulation according to claim 12, wherein said pH adjuster is hydrochloric acid, sodium hydroxide, citric acid, phosphoric acid, lactic acid, tartaric acid, succinic acid, or mixtures thereof.
- 14. The pharmaceutical formulation according to claim 13, wherein said pH adjuster is hydrochloric acid.
- 15. The pharmaceutical formulation according to claim 1, wherein the pH of said formulation ranges from about 2.5 to about 6.0.
- 16. The pharmaceutical formulation according to claim 15, wherein the pH of said formulation ranges from about 3.0 to about 4.5.
- 17. The pharmaceutical formulation according to claim 16, wherein the pH of said formulation ranges from about 3.8 to about 4.2.
- 18. The pharmaceutical formulation according to claim 1 wherein said aqueous diluent is water, normal saline, 5% dextrose solution, or mixtures thereof.
- 19. The pharmaceutical formulation according to claim 3, wherein said dissolution enhancing agent is urea and wherein said pharmaceutical formulation further comprises hydrochloric acid, at least one citrate buffer, and mannitol.
- 20. The pharmaceutical formulation according to claim 18, wherein said antineoplastic agent is present in an amount ranging from about 1 wt % to about 50 wt %, said hydrochloric acid is present in an amount ranging from about 1 wt % to about 20 wt %, said citrate buffer(s) is present in an amount ranging from about 5 wt % to about 60 wt %, said urea is present in an amount ranging from about 4 wt % to about 60 wt %, and said mannitol is present in an amount ranging from about 10 wt % to about 85 wt %.
- 21. The pharmaceutical formulation according to claim 3, wherein said dissolution enhancing agent is L-histidine, L-threonine, L-asparagine, L-serine, L-glutamine or mixtures thereof, and wherein said pharmaceutical formulation further comprises polysorbate, hydrochloric acid, at least one citrate buffer, mannitol, and water.
- 22. The pharmaceutical formulation according to claim 21, wherein said Temozolomide is present in an amount ranging from about 1 wt % to about 50 wt %, said hydrochloric acid is present in an amount ranging from about 1 wt % to about 20 wt %, said citrate buffer(s) is present in an amount ranging from about 5 wt % to about 60 wt %, said polysorbate is present in an amount ranging from about 1 wt % to about 50 wt %, said L-histidine, L-threonine, L-asparagine, L-serine, L-glutamine, or mixtures thereof, is present in an amount ranging from about 2 wt % to about 60 wt %, and said mannitol is present in an amount ranging from about 15 wt % to about 85 wt %.
- 23. A process of making a pharmaceutical formulation comprising the steps of:
(i) dissolving at least one dissolution enhancing agent in at least one aqueous diluent wherein said dissolution enhancing agent is urea, L-histidine, L-threonine, L-asparagine, L-serine, L-glutamine or mixtures thereof; and (ii) adding at least one antineoplastic agent or a pharmaceutically acceptable salt thereof.
- 24. The process according to claim 23 further comprising:
a) adding at least one bulking agent; b) adding at least one buffer; c) adding at least one pH adjuster to form a solution; and d) filtering said solution.
- 25. The process according to claim 24, further comprising lyophilizing said solution from step (d) to form a lyophilized powder.
- 26. The lyophilized powder, produced by the process of claim 25.
- 27. An article of manufacture comprising a container containing the lyophilized powder of claim 26.
- 28. The article of manufacture according to claim 27, wherein said container is a syringe or vial.
- 29. The article of manufacture according to claim 27, further comprising a volume of at least one aqueous diluent suitable for reconstitution of said lyophilized powder.
- 30. A pharmaceutical formulation suitable for administration to a patient, said formulation prepared by reconstituting the lyophilized powder of claim 26 in a volume of at least one aqueous diluent.
- 31. A process for treating or preventing disease in a patient comprising administering a therapeutically effective amount of the pharmaceutical formulation of claim 1 to a patient in need thereof.
- 32. The process for treating or preventing disease according to claim 31, wherein said disease is carcinoma, sarcoma, melanoma, glioma, glioblastoma, brain cancer, lung cancer, thyroid follicular cancer, pancreatic cancer, breast cancer, bladder cancer, myelodysplasia, prostate cancer, testicular cancer, anaplastic astrocytoma, colon and rectal cancer, lymphoma, leukemia, or mycosis fungoides.
- 33. The process for treating or preventing disease according to claim 31, wherein said patient is an animal.
- 34. The process for treating or preventing disease according to claim 31, wherein said patient is a mammal.
- 35. The process for treating or preventing disease according to claim 31, wherein said patient is a human.
- 36. A process for treating or preventing disease in a patient comprising administering a therapeutically effective amount of the pharmaceutical formulation of claim 30 to a patient in need thereof.
- 37. The process for treating or preventing disease according to claim 36, wherein said disease is carcinoma, sarcoma, melanoma, glioma, glioblastoma, brain cancer, lung cancer, thyroid follicular cancer, pancreatic cancer, breast cancer, bladder cancer, myelodysplasia, prostate cancer, testicular cancer, anaplastic astrocytoma, colon and rectal cancer, lymphoma, leukemia, or mycosis fungoides.
- 38. The process for treating or preventing disease according to claim 36, wherein said patient is an animal.
- 39. The process for treating or preventing disease according to claim 36, wherein said patient is a mammal.
- 40. The process for treating or preventing disease according to claim 36, wherein said patient is a human.
Parent Case Info
[0001] This application claims priority from U.S. provisional patent application, Serial No. 60/359,198 filed Feb. 22, 2002.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60359198 |
Feb 2002 |
US |