Efficient brinzolamide and brimonidine compositions

Abstract

Disclosed herein are pharmacologically acceptable and ophthalmologically suitable compositions and methods of their use in treating ophthalmic diseases or related conditions. In aspects, the invention provides compositions comprising effective amounts of carbonic anhydrase inhibitor(s) and alpha-2-adrenergic agonist(s). In facets, compositions comprise a penetration enhancer component comprising one or more penetration enhancer compound(s)/molecule(s). In aspects, the invention provides compositions comprising effective amounts of brimonidine compound(s) and brinzolamide compound(s) capable of being administered once or twice daily for the treatment of elevated intraocular pressure, but which provide similar efficacy to a similar or substantially identical reference product requiring administration three times per day. In facets, the invention provides compositions capable of being administered at a frequency resulting in providing a lower total dose of both brinzolamide and brimonidine compound(s) to a recipient, but nonetheless are as or more effective in IOP control as such similar or substantially identical reference products.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This patent application claims priority to U.S. Provisional Patent Application No. 63 / 087,657 filed Oct. 5, 2020, entitled “Brinzolamide and Brimonidine Ophthalmic Composition”. This application claims the benefit of priority to, and incorporates by reference the entirety of, this above-referenced priority application.FIELD OF THE INVENTION[0002]The invention primarily relates to the field of topical compositions and methods of their use in reducing elevated intraocular pressure and other ophthalmic conditions.BACKGROUND OF THE INVENTION[0003]About 10 out of every 100 people over the age of 40 years of age suffer from elevated intraocular pressure (IOP). A subset of this population experiences elevated IOP, or ocular hypertension, in association with glaucoma, most commonly open-angle glaucoma. Left untreated, ocular hypertension can itself lead to glaucoma, as increased ocular pressure can cause erosion of the optic nerve. Often times su...

AI Technical Summary

Benefits of technology

[0055]In specific embodiments, the invention provides pharmaceutically acceptable and ophthalmologically suitable compositions comprising brinzolamide compound in an amount of between about 0.1 wt. %-about 10 wt. % of the composition and a brimonidine compound in an amount of between about 0.01 wt. %-about 0.5 wt. % of the composition. In aspects, the brimonidine compound is brimonidine tartrate. In aspects, compositions further comprise an effective amount of a borate-polyol complex. In aspects, the total of one or more borate-polyol complexes present in composition make(s) up about 0.5 wt. %-about 6 wt. % of the composition. In aspects, compositions further comprise an effective penetration enhancer component.

[0056]In certain facets, the invention provides pharmaceutically acceptable and ophthalmologically suitable compositions comprising: (a) a brinzolamide compound in an amount of between about 0.1 wt. %-about 10 wt. % of the composition; (b) a brimonidine compound in an amount of between about 0.01 wt. %-about 0.5 wt. % of the composition; (c) one or more borate-polyol complexes, wherein the total of the one or more borate-polyol complexes are present in an amount of between about 0.5 wt. %-about 6 wt. % of the composition; and (d) benzalkonium chloride in an amount between 0.005-about 0.02 wt. % of the composition. In aspects, the brimonidine compound is brimonidine tartrate.

[0057]The invention provides a composition comprising any of the active ingredient(s) and optionally other ingredient(s)/component(s) described above in this section, wherein the composition, when administered to a subject, once or twice per 24-hour period, demonstrates bioequivalence to; or demonstrate detectably or significantly improved pharmacokinetic properties or clinical results over; a similar or substantially identical reference product administered three times per day. In aspects, the reference product is an FDA approved reference product including brinzolamide and brimonidine for ophthalmologic application(s). In aspects, the FDA reference product is the currently FDA approved and marketed version of Simbrinza® (ALCON) (the details of which are described below). In aspects, bioequivalence is determined by the performance of an FDA-approved clinical endpoint study. In aspects, bioequivalence is determined by the performance of a clinical endpoint study performed substantially in accordance with FDA guidance/recommendations, except with respect to frequency of administration of the composition and the reference product. In aspects, the invention provides improved brinzolamide and brimonidine ophthalmic composition demonstrating greater bioavailability, tolerability, retention time, patient compliance, and reduced dosing frequency over that of reference product(s).

[0058]In embodiments, the invention provides methods of treating ocular hypertension or elevated intraocular pressure (IOP), comprising administration of a pharmaceutically acceptable and ophthalmologically suitable composition comprising a brinzolamide compound in an amount of between about 0.1 wt. %-about 10 wt. % of the composition and a brimonidine compound in an amount of between about 0.01 wt. %-about ...

Problems solved by technology

Left untreated, ocular hypertension can itself lead to glaucoma, as increased ocular pressure can cause erosion of the optic nerve.

Often times such erosion of the optic nerve leads to vision loss and even blindness.

Brimonidine tartrate is known for its somewhat significant side effects.

As monotherapy may be insufficient to successfully treat elevated IOP, multidrug regimens have been proposed.

However, as described in, e.g., Nguyen, “Combination of brinzolamide and brimonidine for glaucoma and ocular hypertension: critical appraisal and patient focus,” (Patient Prefer Adherence; 2014; 8: 853-864), multidrug regimens can be complex and introduce significant risks, such as preservative-related effects and may potentially reduce overall drug exposure as a consequence of drug washout during closely t...

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