Ophthalmic formulations of tyrosine kinase inhibitors, methods of use thereof, and preparation methods thereof
Inventors
Assignees
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Publication Number
US-10154994-B2
Publication Date
2018-12-18
Expiration Date
Abstract
Ophthalmic formulations containing tyrosine kinase inhibitors, such as Nintedanib, Axitinib, Sorafenib, and Pazopanib are described. The ophthalmic formulations can contain microparticles or nanoparticles of the tyrosine kinase inhibitor. Also described are methods of using the ophthalmic formulations for treating ocular surface diseases, such pterygium, including recurrent pterygium, and hyperemia associated with pterygium.
Core Innovation
The invention relates to ophthalmic formulations and therapeutic methods using tyrosine kinase inhibitors for treating pterygium or a symptom thereof. It provides aqueous suspensions for topical administration to an eye, where the active ingredient is nintedanib in the form of particles or a pharmaceutically acceptable salt thereof. The formulations further include tyloxapol and a viscosity regulator.
A central aspect of the disclosed core is delivering nintedanib as microparticles or nanoparticles in an aqueous suspension. The disclosed formulations include aqueous microsuspensions and aqueous nanosuspensions, with particle-size criteria expressed via D10/D50/D90 and, for nanosuspensions, additional parameters such as pH and tonicity/isotonicity.
The therapeutic concept is to treat pterygium and pterygium-associated symptoms such as hyperemia and anterior-segment lesion neovascularization. The document indicates treatment outcomes including regression of pterygium lesions, prevention of recurrence and/or reduced recurrence rate, and inhibition or reduction of lesion neovascularization.
Claims Coverage
Three independent claims define the claimed treatment methods. Across the independent claims, the inventive features center on topical administration of an aqueous suspension or nanosuspension containing nintedanib particles, tyloxapol, and a specified viscosity regulator, together with quantitative composition and particle-size criteria.
Topical aqueous suspension with nintedanib particles, tyloxapol, and viscosity regulator
A method of treating pterygium or a symptom thereof in a subject in need thereof by administering to an eye an aqueous suspension comprising nintedanib particles or a pharmaceutically acceptable salt thereof, tyloxapol, and a viscosity regulator in specified concentration ranges.
Topical aqueous nanosuspension with nintedanib nanoparticles, tyloxapol, and HPMC
A method of treating pterygium or a symptom thereof in a subject in need thereof by topically administering to an eye an aqueous nanosuspension comprising nintedanib nanoparticles or nanoparticles of a pharmaceutically acceptable salt thereof, tyloxapol, and hydroxypropylmethylcellulose (HPMC) in specified concentration ranges.
Topical aqueous suspension of nintedanib ethanesulfonate nanoparticles with D90 criterion
A method of treating pterygium or a symptom thereof in a subject in need thereof by topically administering to an eye an aqueous suspension comprising nintedanib ethanesulfonate nanoparticles and at least one pharmaceutically acceptable excipient, wherein the particles have a D90 particle size of less than 1.5 μm as measured by dynamic light scattering.
Overall claim coverage focuses on topical treatment of pterygium using aqueous particle suspensions of nintedanib, including nintedanib ethanesulfonate nanoparticles, combined with tyloxapol and viscosity regulators including HPMC. The independent-claim boundaries are enforced by specified component concentration ranges and, in at least one independent claim, a particle-size criterion based on D90 measured by dynamic light scattering.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Topical treatment of pterygium, including recurrent pterygium, and pterygium-associated hyperemia in a subject.
Treatment aims including regression of corneal pterygium lesions, prevention of recurrence and/or reduction in recurrence rate, and inhibition or reduction of anterior-segment lesion neovascularization.
Efficacy assessment using a cornea suture-induced neovascularization model and ocular tolerability assessment in rabbits.
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