Compositions and methods for the treatment of intraocular neovascularization and/or leakage
The invention provides compositions and methods for the treatment of intraocular neovascularization and/or leakage including wet age-related macular degeneration. The compositions preferably use tyrosine kinase inhibitors with an IC50 for VEGFR2 of 20 nanomolars or less and an IC50 for c-MET of 20 nanomolars or less.
1. A method for treating a disease caused by intraocular neovascularization or leakage selected from the group consisting of diabetic macular edema and diabetic proliferative retinopathy, comprising administering to a patient in need thereof an ophthalmological composition comprising an active ingredient consisting of one or more tyrosine kinase inhibitors selected from the group consisting of axitinib, cabozantinib, foretinib, regorafenib, ponatinib, motesanib, cediranib, tivozanib, sorafenib, LY2457546, MGCD-265, MGCD-510, tivantinib, AMG458, JNJ-3887, EMD1214063, BMS794833, PHI1665752, SGX-523 and INCB280 or any pharmaceutically acceptable salts or esters thereof, wherein the route of administration is topical, subconjunctival injection, intravitreal injection or a combination thereof.
2. The method of claim 1 wherein the ophthalmological composition further comprises a surfactant.
3. The method of claim 1 wherein the ophthalmological composition further comprises propanediol at a concentration from about 1% to about 10% weight by total volume of the composition.
4. The method of claim 3 further comprising one or more surfactants or lipid solubilizers each at a concentration from about 1% to about 21% weight by total volume of the composition.
5. The method of claim 4 wherein the one or more surfactants or lipid solubilizers is selected from the group consisting of sodium lauryl ether sulfate, sodium lauryl sulfate, dimethyl isosorbide, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan monooleate, polysorbate 20-80, a cyclodextrin, squalene, a second propylene glycol, a polyethylene glycol, a poloxamer, a polyoxyl and a combination thereof.
6. The method of claim 5 wherein the one or more surfactants or lipid solubilizers is sodium lauryl sulfate at a concentration from about 0.5% to about 10.0% weight by total volume of the composition.
7. The method of claim 6 further comprising a viscosity enhancer selected from the group consisting of carboxymethyl cellulose, carboxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, and hydroxypropylmethyl cellulose and a combination thereof.
8. The method of claim 1 wherein the one or more tyrosine kinase inhibitors is one tyrosine kinase inhibitor selected from the group consisting of cabozantinib, foretinib, MGCD-265 and MGCD-510.