Preservative free ocular compositions and methods for using the same for treating dry eye disease and other eye disorders
Inventors
Jain, Sandeep • Kompella, Uday Bhaskar • Musunuri, Shankar
Assignees
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Publication Number
US-10751337-B2
Publication Date
2020-08-25
Expiration Date
Abstract
The present invention provides a preservative free ophthalmic formulation. In particular, the ophthalmic formulations of the invention are aqueous formulations comprising nanoemulsion of oil. The present invention also provides a method for treating an eye disorder. In one particular embodiment, the invention provides methods for treating dry eye syndrome using an preservative free formulation comprising a nanoemulsion of oil and alpha 2 adrenergic agonist, pharmaceutically acceptable salt thereof or a mixture thereof. In particular, the alpha 2 adrenergic agonist of the invention has a higher alpha 2A agonist activity compared to alpha 2B agonist activity. This invention also provides a preservative free ophthalmic composition comprising a nanoemulsion of oil, a therapeutically effective amount of an alpha 2 adrenergic agonist, a pharmaceutically acceptable salt thereof or a combination thereof as an active ingredient for treating a dry eye syndrome.
Core Innovation
The invention provides a preservative free aqueous ophthalmic solution that consists of an alpha 2 adrenergic agonist, a nanoemulsion of oil, a pharmaceutically acceptable excipient, and water. The formulation is preservative free and is based on an oil nanoemulsion in an aqueous ophthalmic solution context, with embodiments in which the alpha 2 adrenergic agonist is a pharmaceutically acceptable salt and is used in combination forms.
A key aspect of the invention is combining the alpha 2 adrenergic agonist with the oil nanoemulsion, including embodiments where the brimonidine is largely in the nanoemulsion oil phase or mainly in the aqueous phase. The disclosed embodiments include selecting excipients and using a nanoemulsion with droplet size targets, including droplet sizes around 200 nm or less.
The invention is directed to treating dry eye disorders and related ocular conditions using the preservative free formulation. The disclosed dry eye targets include aqueous tear-deficient dry eye (ADDE), evaporative dry eye (EDE), mixed mechanism dry eye, Meibomian gland dysfunction, ocular GVHD, Sjogren's dry eye syndrome, and LASIK-related dry eye, as well as administration concepts including direct administration to the eyelid margin.
Claims Coverage
The patent includes two independent claims, covering a preservative free aqueous ophthalmic solution composition and a method of treating dry eye syndrome by administering the formulation. Across the dependent claims, the inventive features refine alpha 2 adrenergic agonist selectivity and identity, nanoemulsion oil characterization including droplet size, excipient selection categories, and treatment targeting and administration context for dry eye subtypes and etiologies.
Preservative free aqueous ophthalmic solution with alpha 2 adrenergic agonist and oil nanoemulsion
A preservative free aqueous ophthalmic solution consisting of an alpha 2 adrenergic agonist, a pharmaceutically acceptable salt thereof, or a combination thereof; a nanoemulsion of oil; a pharmaceutically acceptable excipient; and water.
Higher alpha 2A agonist activity than alpha 2B agonist activity
The alpha 2 adrenergic agonist has higher alpha 2A agonist activity than alpha 2B agonist activity.
Nanoemulsion droplet size less than 200 nm
The nanoemulsion has a droplet size of less than 200 nm.
Brimonidine as the alpha 2 adrenergic agonist
The alpha 2 adrenergic agonist is brimonidine, a pharmaceutically acceptable salt of brimonidine, or a combination of them.
Selected oils in the nanoemulsion oil phase
The nanoemulsion of oil contains one or more selected oils from castor, olive, soy, corn, mineral, cottonseed, safflower, and sesame.
Excipient chosen from specified excipient categories
The pharmaceutically acceptable excipient is chosen from crosslinking agents, surfactants, gums, resins, pH adjusters, stabilizers, antioxidants, ultraviolet absorbents, wetting agents, or combinations thereof.
Treating dry eye syndrome by administering a preservative free oil nanoemulsion formulation with alpha 2 adrenergic agonist
A method of treating a patient suffering from a dry eye syndrome comprising administering to an eye of the patient in need of such a treatment a preservative free ophthalmic formulation consisting of nanoemulsion of oil, and a therapeutically effective amount of an alpha 2 adrenergic agonist, a pharmaceutically acceptable salt thereof, or a combination thereof.
Administering directly to the eyelid margin
The formulation is administered directly to the patient’s eyelid margin.
Treatment targeted to aqueous tear-deficient dry eye (ADDE)
Where the dry eye syndrome is aqueous tear-deficient dry eye (ADDE).
Dry eye syndrome causes including LASIK-related and specified contributory causes
The dry eye syndrome is caused by LASIK refractive surgery or by one or more specified causes including vitamin A deficiency, ocular surface disorders, allergy, aging, contact lens usage, medication usage, and disorders of eyelid aperture.
Overall, the claims cover a preservative free aqueous ophthalmic formulation combining an alpha 2 adrenergic agonist with an oil nanoemulsion and specified excipients, with dependent features including alpha 2A activity preference, brimonidine identity, droplet size, selected oils, and excipient categories. The method claims use the same formulation to treat dry eye syndrome, refined by target subtype, eyelid margin administration, and etiologies including LASIK-related and listed contributory causes.
Stated Advantages
Avoiding preservative-associated corneal and conjunctival toxicity.
Improving patient symptoms and eyelid margin and Meibomian gland dysfunction (MGD) signs.
Providing dry eye disorder treatment for aqueous tear-deficient dry eye (ADDE), evaporative dry eye (EDE), and mixed mechanism dry eye, including Meibomian gland dysfunction.
Documented Applications
Treating dry eye syndrome, including aqueous tear-deficient dry eye (ADDE), evaporative dry eye (EDE), and mixed mechanism dry eye.
Treating Meibomian gland dysfunction (MGD).
Treating ocular GVHD and Sjogren's dry eye syndrome.
Treating LASIK-related dry eye.
Treatment embodiments include administration concepts directed to the eyelid margin.
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