JPWO2020018778A5 - - Google Patents

Claims (25)

a) Poly(lactic acid)-poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) (PLA-PEG-PPG-PEG) tetrablock copolymer , poly(lactic acid)-poly(ethylene glycol)- Poly(propylene glycol)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PPG-PEG-PLA) pentablock copolymer or poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) A pharmaceutical composition comprising polymeric nanoparticles comprising a block copolymer ; and b) salinomycin; and c) a pharmaceutically acceptable carrier. 2. The pharmaceutical composition of claim 1 , wherein said PLA-PEG-PPG-PEG tetrablock copolymer is formed from a chemical conjugation of a PEG-PPG-PEG triblock copolymer and PLA. 3. The pharmaceutical composition of claim 1 or 2 , wherein the PLA has a molecular weight of about 10,000 to about 100,000 Daltons. The pharmaceutical composition according to any one of claims 1-3 , wherein the PLA has a molecular weight of about 20,000-90,000 Daltons. The pharmaceutical composition according to any one of claims 1-4 , wherein the PLA has a molecular weight of about 30,000-80,000 Daltons. The pharmaceutical composition according to any one of claims 1-5 , wherein the PEG-PPG-PEG has a molecular weight of about 8,000 Daltons to 18,000 Daltons. The pharmaceutical composition according to any one of claims 1-6 , wherein the PEG-PPG-PEG has a molecular weight of about 12,000 Daltons to 17,000 Daltons. Claims 1-7 , wherein the molecular weight of PLA in the copolymer is about 30,000-80,000 Daltons and the molecular weight of PEG-PPG-PEG is about 12,000-17,000 Daltons. The pharmaceutical composition according to any one of The pharmaceutical composition according to any one of claims 1-8 , wherein the polymeric nanoparticles have an average diameter of about 80 to about 120 nm. The pharmaceutical composition according to any one of claims 1-9 , wherein the polymeric nanoparticles have an average diameter of about 90 to about 110 nm. The pharmaceutical composition according to any one of claims 1-10 , wherein the polymeric nanoparticles have an average diameter of about 95 to about 105 nm. The pharmaceutical composition according to any one of claims 1-11 , further comprising a second therapeutic agent or targeted anti-cancer agent. 13. The pharmaceutical composition of any one of claims 1-12, wherein the polymeric nanoparticles further comprise a targeting moiety attached to the exterior of the polymeric nanoparticles. A dosage form comprising from about 12.5 mg to about 500 mg of the pharmaceutical composition of any one of claims 1-13. 15. A pharmaceutical composition or dosage form according to any one of claims 1 to 14 for use in reducing the proliferation, survival, migration or colony forming ability of rapidly proliferating cells in a subject in need thereof. 16. The pharmaceutical composition or dosage form of claim 15, for administration to a subject from about 0.025 mg/kg to about 5 mg/kg. to administer to the subject from about 0.03 mg/kg to about 0.5 mg/kg, from about 0.5 mg/kg to about 0.8 mg/kg, or from about 0.8 mg/kg to about 1.1 mg/kg; 17. A pharmaceutical composition or dosage form according to claim 15 or 16. A pharmaceutical composition or dosage form for use according to any one of claims 15-17, wherein said cells are cancer cells and/or cancer stem cells . A pharmaceutical composition or dosage form according to any one of claims 1 to 14 for use in treating cancer in a subject in need thereof. 20. The pharmaceutical composition or dosage form of claim 19, for administration to a subject from about 0.025 mg/kg to about 5 mg/kg. to administer to the subject from about 0.03 mg/kg to about 0.5 mg/kg, from about 0.5 mg/kg to about 0.8 mg/kg, or from about 0.8 mg/kg to about 1.1 mg/kg; 21. A pharmaceutical composition or dosage form according to claim 19 or 20. The cancer is breast cancer, triple-negative breast cancer, ovarian cancer, pancreatic cancer, leukemia, lymphoma, osteosarcoma, gastric cancer, prostate cancer, colon cancer, non-small cell lung cancer and small cell lung cancer, liver cancer, kidney A pharmaceutical composition or dosage form for use according to any one of claims 19 to 21 , selected from the group consisting of cancer, head and neck cancer, and cervical cancer. A pharmaceutical composition for use according to any one of claims 19 to 22, wherein said cancer is metastatic or said cancer is resistant or refractory to chemotherapeutic agents or dosage form . 24. A pharmaceutical composition or dosage form according to any one of claims 19 to 23 for use in combination with an additional anti-cancer therapy , optionally wherein said additional anti-cancer therapy is , surgery, chemotherapy, radiation, hormone therapy, immunotherapy, or a combination thereof . A pharmaceutical composition or dosage form for use according to any one of claims 15-24, wherein said subject is a human.