Ophthalmic compositions and methods of use
Inventors
Musunuri, Shankar • Jain, Sandeep • Arumugham, Rasappa • Upadhyay, Arun K. • Nudell, Matthew • Somasekhar, Gopalam
Assignees
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Publication Number
US-10555947-B2
Publication Date
2020-02-11
Expiration Date
Abstract
The present invention provides a composition comprising two or more of the following pharmaceutically active compounds: (i) an alpha 2 adrenergic agonist; (ii) a corticosteroid; (iii) a lymphocyte function-associated antigen antagonist; (iv) a non-steroidal anti-inflammatory drug (NSAID); (v) a sodium channel blocker; and (vi) an antibiotic, provided at least one of the pharmaceutically active compound is selected from the group consisting of (i) alpha 2 adrenergic agonist and (ii) corticosteroid. The present invention also provides a method for using such composition to treat an eye disorder such as a dry eye syndrome; ocular graft-versus-host-disease; ocular rosacea; allergic conjunctivitis; autoimmune ocular surface disease; thygeson's superficial punctuate keratopathy; herpes zoster keratitis; Stevens-Johnson syndrome; keratitis; conjunctivitis; blepharitis; blepharochalasis; conjunctivochalasis; blepharoconjunctivitis; blepharokeratoconjunctivitis; post-operative inflammation or pain from ocular surgery; scleritis; episcleritis; anterior uveitis; iritis; cyclitis; ocular surface vascular disorder; ulcerative keratitis; photokeratitis; dacryocystitis; eyelid disorder; congenital alacrima; xerophthalmia; dacryoadenitis; vernal keratoconjunctivitis; pinguecula; and/or ocular surface disorder induced by chemical burns, thermal burns, or physical insult to the ocular surface.
Core Innovation
The invention relates to ophthalmic compositions and topical administration for treating dry eye syndrome and other eye disorders, including aqueous tear deficient dry eye, evaporative dry eye, ocular surface and eyelid disorders, ocular graft-versus-host disease, ocular rosacea, allergic conjunctivitis, and autoimmune ocular surface disease. The compositions include an alpha 2 adrenergic agonist and cyclosporin, and the alpha 2 adrenergic agonist is associated with alpha-2A adrenergic receptor and alpha-2B adrenergic receptor activity.
The invention addresses limitations of single-agent approaches for these disorders and provides combination therapeutics. The disclosed compositions may be homogeneous or heterogeneous aqueous solutions, including emulsions and suspensions, with particular discussion of oil-in-water nanoemulsions/suspensions and heterogeneous aqueous solutions.
The disclosed compositions may also include additional agents such as a lymphocyte function-associated antigen antagonist, lifitegrast, corticosteroids, loteprednol etabonate, NSAIDs, sodium channel blockers, ENaC inhibitors including amiloride and derivatives, and antibiotics. Multi-API formulations are described as yielding synergistic effects and reduced side effects.
Claims Coverage
The provided independent claim set centers on an ophthalmic composition that combines an alpha 2 adrenergic agonist with cyclosporin, with dependent claims refining the identity, concentration, and formulation type, and additional dependent claims directing topical treatment of selected eye disorders using a therapeutically effective amount.
Alpha 2 adrenergic agonist and cyclosporin ophthalmic composition
An ophthalmic composition comprising an alpha 2 adrenergic agonist and cyclosporin.
Brimonidine selection for the alpha 2 adrenergic agonist
The alpha 2 adrenergic agonist is selected from brimonidine, a pharmaceutically acceptable salt of brimonidine, or a combination of these.
Alpha-2 adrenergic agonist concentration range
The composition contains the alpha-2 adrenergic agonist at about 0.01% to about 0.5% w/w of the total composition.
Heterogeneous aqueous solution formulation
The composition is a heterogeneous aqueous solution.
Nanoemulsion emulsion formulation
The composition is an emulsion that is specifically a nanoemulsion.
Topical treatment of a selected eye disorder with a therapeutically effective amount
A method for treating a selected eye disorder, including dry eye syndrome or an ocular surface and eyelid disorder, by administering to a subject a therapeutically effective amount of the composition.
Overall, the claim coverage is anchored in a combination ophthalmic composition of an alpha 2 adrenergic agonist with cyclosporin, and is further narrowed by specifying brimonidine as a representative agonist, a defined w/w concentration range, heterogeneous aqueous formulations including nanoemulsions, and topical therapeutic use for specified classes of eye disorders using a therapeutically effective amount.
Stated Advantages
The multi-API formulations are described as yielding synergistic effects versus single-agent therapy.
The multi-API formulations are described as yielding reduced side effects versus single-agent therapy.
In a mouse dry-eye disease model, statistically significant reductions in corneal inflammation and/or fluorescein staining are reported compared with placebo and marketed cyclosporine/lifitegrast products.
Documented Applications
Treatment of dry eye syndrome, including aqueous tear deficient dry eye and evaporative dry eye, using the disclosed ophthalmic compositions with topical administration.
Treatment of ocular graft-versus-host disease, ocular rosacea, allergic conjunctivitis, and autoimmune ocular surface disease.
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