Ophthalmic formulations including selective alpha 1 antagonists

Abstract

Ophthalmic formulations are provided. The ophthalmic formulations include one or more active agents that act to optimize pupil light reflex while minimizing, or effectively eliminating, any undesired eye redness in response to application thereof. The active agents include, for example, alpha 1 antagonists, such as alpha 1a selective antagonists.

The invention is claimed as follows: 
     
         1 . An ophthalmic formulation in an emulsified form for topical administration, the ophthalmic formulation comprising:
 a sterile aqueous carrier including an ophthalmic artificial tear solution, and   a therapeutically effective amount of an alpha 1 antagonist that selectively effects an iris alpha adrenergic receptor over a vascular alpha adrenergic receptor for optimizing a pupil diameter in a reduced light while minimizing eye redness,   wherein the alpha 1 antagonist is selected from the group consisting of sulfonamides including tamsulosin; uracils including A-131701, fiduloxasin, Ro-70-004, urapidil and 5-methyl urapidil; piperidines including 4-oxospiro benzopyran-2,4-piperidine; arylpiperazines including RWJ-38063, RWJ-68141, RWJ-68157, RWJ-69736, Ro-70-004, REC 15/2739, SB216469, urapidil and 5-methyl urapidil; dihydropyridines including SNAP 5089 and niguldipine; aminobenzodioxanes including WB 4101; dihydroindoles including RS 17053; n-alkylated saccharins; and derivatives thereof.   
     
     
         2 . The ophthalmic formulation of  claim 1 , wherein the alpha 1 antagonist is selective for an iris dilator smooth muscle alpha adrenergic receptor. 
     
     
         3 . The ophthalmic formulation of  claim 2 , wherein the alpha 1 antagonist effectively reduces activity of the iris dilator smooth muscle. 
     
     
         4 . The ophthalmic formulation of  claim 3 , wherein the alpha 1 antagonist reduces activity of the iris dilator muscle effectively without constriction of an iris sphincter muscle. 
     
     
         5 . The ophthalmic formulation of  claim 1 , wherein the alpha 1 antagonist is selective for an alpha 1a adrenergic receptor over an alpha 1b adrenergic receptor. 
     
     
         6 . The ophthalmic formulation of  claim 1 , wherein the ophthalmic formulation is in an eye dropper. 
     
     
         7 . The ophthalmic formulation of  claim 1 , wherein the ophthalmic artificial tear solution includes hydroxypropyl methylcellulose in an amount of about 0.2% to 1.5% by weight of the ophthalmic artificial tear solution. 
     
     
         8 . The ophthalmic formulation of  claim 1 , wherein the pupil diameter is 6 mm or greater. 
     
     
         9 . The ophthalmic formulation of  claim 1 , wherein the pupil diameter is optimized to 6 mm or less. 
     
     
         10 . The ophthalmic formulation of  claim 1 , wherein the pupil diameter ranges from about 3 mm to about 5 mm. 
     
     
         11 . The ophthalmic formulation of  claim 1 , wherein the ophthalmic formulation does not affect a pupil diameter at about 2 mm or less in a bright light. 
     
     
         12 . The ophthalmic formulation of  claim 1 , wherein a pupil diameter is optimized by reduction by about 1 mm or more. 
     
     
         13 . The ophthalmic formulation of  claim 1 , wherein a pupil diameter is optimized by reduction by about 20% or more. 
     
     
         14 . The ophthalmic formulation of  claim 1 , wherein the ophthalmic formulation reduces an adverse visual effect. 
     
     
         15 . The ophthalmic formulation of  claim 14 , wherein the adverse visual effect is at least one of a perceived light scattering, a reduced contrast sensitivity and a reduced acuity. 
     
     
         16 . The ophthalmic formulation of  claim 14 , wherein the adverse visual effect is due to at least one of an imperfect aspheric peripheral corneal curvature; a higher order aberration of the eye selected from the group consisting of a coma, a secondary astigmatism, a spherical aberration, a trifoil, a quadrafoil, and a tetrafoil; an uncorrected spherocylindrical correction contributed to by peripheral zones of a cornea; and combinations thereof. 
     
     
         17 . The ophthalmic formulation of  claim 1 , wherein the ophthalmic formulation promotes corneal absorption over vascular effect via a chemical modulation of a vascular tissue. 
     
     
         18 . The ophthalmic formulation of  claim 17 , wherein the chemical modulation includes a temporary shielding or binding to a conjunctiva of the eye. 
     
     
         19 . The ophthalmic formulation of  claim 17 , wherein the chemical modulation increases corneal absorption without effect on vascular absorption. 
     
     
         20 . The ophthalmic formulation of  claim 17 , wherein the chemical modulation occurs through exposure to one or more substances selected from the group consisting of a bioflavonoid, vitamin A, and substances derived from fruits and vegetables in order to reduce capillary permeability, including herbal extracts including aescin. 
     
     
         21 . The ophthalmic formulation of  claim 17 , wherein the chemical modulation occurs through use of one or more substances selected from the group consisting of a bioflavonoids, vitamin A, substances derived from fruits and vegetables in order to reduce capillary permeability, herbal extracts including aescin demulcents, horse chestnut extracts, a substance containing mucilage, azone, a collagen corneal shield, a cyclodextrin including a charged cyclodextrin and a sulfated cyclodextrin, a bioadhesive polymer, a microsphere, a chitosan, a captisol; and combinations thereof. 
     
     
         22 . The ophthalmic formulation of  claim 1 , wherein the ophthalmic formulation protects a mucous membrane of the eye from chemical irritants, to soothe the eye and/or to reduce redness, burning, stinging, or dryness by a method selected from the group of binding a protective layer to the mucous membrane of the eye and the conjunctiva; by reducing a capillary permeability of the eye and increasing a venous tone by using bioflavonoids; and combinations thereof. 
     
     
         23 . The ophthalmic formulation of  claim 1 , wherein the ophthalmic formulation increases chemical absorption via one or more carrier particles selected from the group consisting of nanoparticles including liposomes and emulsions, dendrimers, and buckeyballs. 
     
     
         24 . A method of modulating pupil dilation, the method comprising: administering to an eye of an individual an ophthalmic formulation in an emulsified form comprising a sterile aqueous carrier including an ophthalmic artificial tear solution, and a therapeutically effective amount of an alpha 1 antagonist that selectively effects an iris alpha adrenergic receptor over a vascular alpha adrenergic receptor; and allowing the ophthalmic formulation to remain in contact with the eye for a period of time in a reduced light where a dilator muscle of the eye receives greater stimulation in absence of the ophthalmic formulation and eye redness is minimized, wherein the alpha 1 antagonist is selected from the group consisting of sulfonamides including tamsulosin; uracils including A-131701, fiduloxasin, Ro-70-004, urapidil and 5-methyl urapidil; piperidines including 4-oxospiro benzopyran-2,4-piperidine; arylpiperazines including RWJ-38063, RWJ-68141, RWJ-68157, RWJ-69736, Ro-70-004, REC 15/2739, SB216469, urapidil and 5-methyl urapidil; dihydropyridines including SNAP 5089 and niguldipine; aminobenzodioxanes including WB 4101; dihydroindoles including RS 17053; n-alkylated saccharins; and derivatives thereof. 
     
     
         25 . A method of administering an ophthalmic formulation comprising a sterile aqueous carrier including an ophthalmic artificial tear solution to an eye of an individual comprising administering a therapeutically effective amount of an alpha 1 antagonist within the ophthalmic formulation that selectively effects an iris alpha adrenergic receptor over a vascular alpha adrenergic receptor wherein the ophthalmic formulation optimizes a pupil diameter while effectively minimizing eye redness, wherein the alpha 1 antagonist is selected from the group consisting of sulfonamides including tamsulosin; uracils including A-131701, fiduloxasin, Ro-70-004, urapidil and 5-methyl urapidil; piperidines including 4-oxospiro benzopyran-2,4-piperidine; arylpiperazines including RWJ-38063, RWJ-68141, RWJ-68157, RWJ-69736, Ro-70-004, REC 15/2739, SB216469, urapidil and 5-methyl urapidil; dihydropyridines including SNAP 5089 and niguldipine; aminobenzodioxanes including WB 4101; dihydroindoles including RS 17053; n-alkylated saccharins; and derivatives thereof.