Efflux inhibitor compositions and methods of treatment using the same
OwnerAntonius Martinus Gustave Bunt, Olaf van Tellingeninventors
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Abstract
The present invention relates to efflux inhibitor compositions and methods of using these agents for treating conditions where the activity of efflux transporter proteins (e.g., Breast Cancer Resistance Protein (BCRP) and P-Glycoprotein (P-GP)) inhibit effective delivery of a therapeutic agent to a target tissue (e.g., brain, spinal cord, nerves, cerebrospinal fluid, testis, eyeballs, retina, inner ear, placenta, mammary gland, liver, biliary tract, kidney, intestines, lung, adrenal cortex, endometrium, hematopoietic cells, and/or stem cells).
Claims48
A composition comprising an efflux inhibitor, wherein the efflux inhibitor is formulated to achieve one or more of:
- a. a Cmax of at least 500 ng/ml;
- b. bioavailability of at least 0.2;
- c. an AUC(0-48h) of at least 900 ug/ml*min;
- d. an AUC(0-∞) of at least 1100 ug/ml*min;
- and
- e. an elimination half-life (T1/2) of at least 10 h;
- when the composition is administered by oral gavage at 100 mg/kg to fasted, female Sprague-Dawley rats.
The composition of 16, wherein the solubility enhancer is selected from the group consisting of TPGS, polyethylene glycol 300, polyethylene glycol 400, ethanol, propylene glycol, glycerin, N-methyl-2-pyrrolidone, di methylacetamide, and dimethylsulfoxide, Cremophor EL, Cremophor RH 40, Cremophor RH 60, polysorbate 20, polysorbate 80, Solutol HS 15, sorbitan monooleate, poloxamer 407, Labrafil M-1944CS, Labrafil M-2125CS, Labrasol, Gellucire 44/14, Softigen 767, mono- and di-fatty acid esters of PEG 300, 400, or 1750, water-insoluble lipids, organic liquids/semi-solids, and cyclodextrins.
The composition of 16, wherein the solubility enhancer is poloxamer 407.
The composition of 17, wherein the composition or nanoparticle formulation comprises at least about 5% poloxamer 407 w/w.
A composition comprising a nanoparticle formulation of elacridar, wherein the nanoparticle formulation comprises elacridar and TPGS.
A composition comprising a nanoparticle formulation of elacridar, wherein the nanoparticle formulation comprises elacridar and poloxamer 407.
Dependencies are inferred from the claim text.