Ocular therapy using alpha-2 adrenergic receptor anterior compounds having enhanced clearance rates

Abstract

Ophthalmically therapeutic materials, such as liquid-containing compositions and polymeric drug delivery systems, include a therapeutic component which includes an alpha 2 adrenergic receptor agonist that is cleared from the anterior segment of an individual's eye to which the material is administered. The alpha 2 adrenergic receptor agonist may have a vitreal half-life greater than about three hours. The present materials are effective in treating an ocular condition(s) that affect the anterior segment of an eye, or the anterior and posterior segment of the eye. The materials are suitable for intravitreal or periocular administration and can provide prolonged drug delivery and therapeutic benefits to patients to which the materials have been administered. The alpha 2 adrenergic receptor agonists can be provided in liquid-containing formulations and/or bioerodible and/or non-bioerodible polymeric implants and microparticles. Methods of making and using the present materials are also described.

1 - 24 . (canceled)  
     
     
         25 . A method of improving or maintaining vision of an eye of a patient, comprising the step of administering an ophthalmically therapeutic material to an eye of an individual, wherein said ophthalmically therapeutic material comprises: 
 a therapeutic component comprising a therapeutically effective amount of an alpha 2 adrenergic receptor agonist having a structure effective in providing elimination of the agonist from the anterior chamber of an eye to which the agonist is administered.    
     
     
         26 . The method of  claim 25 , wherein the method is effective to treat an ocular condition selected from the group consisting of anterior ocular condition, posterior ocular conditions, and combinations thereof.  
     
     
         27 . The method of  claim 25 , wherein the method is effective to provide neuroprotection to ocular neuronal cells and to reduce elevated intraocular pressure.  
     
     
         28 . The method of  claim 25 , wherein the method is effective in treating glaucoma.  
     
     
         29 . The method of  claim 25 , wherein the material is administered by a step selected from the group consisting of intraocular administration, periocular administration, and combinations thereof.  
     
     
         30 . The method of  claim 25 , wherein the material is administered by intravitreal injection of the material into the eye.  
     
     
         31 . The method of  claim 25 , wherein the administering comprises subconjunctival administration or periocular administration to deliver the alpha 2 adrenergic receptor agonist to a posterior structure of the eye selected from the group consisting of: the uveal tract, the vitreous, the retina, the choroid, the retinal pigment epithelium, and combinations thereof.  
     
     
         32 . The method of  claim 25 , wherein the administering comprises administering the material to a location in the eye selected from the group consisting of the anterior chamber, the posterior chamber, and combinations thereof.  
     
     
         33 . The method of  claim 25 , wherein the administering comprises using a syringe or a trocar to administer the material to the eye.  
     
     
         34 . The method of  claim 25 , wherein said ophthalmically therapeutic material further comprises a polymeric component associated with a therapeutic component in the form of a polymeric drug delivery system suitable for administration to a patient by at least one of intravitreal administration and periocular administration.  
     
     
         35 . The method of  claim 34 , wherein the polymeric drug delivery system is selected from the group consisting of biodegradable polymeric implants, non-biodegradable polymeric implants, biodegradable polymeric microparticles, and combinations thereof.  
     
     
         36 . The method of  claim 34 , wherein the polymeric component comprises a poly(lactide-co-glycolide) polymer.  
     
     
         37 . The method of  claim 34 , wherein the polymeric component comprises a polymer selected from the group consisting of poly-lactic acid (PLA), poly-glycolic acid (PGA), poly-lactide-co-glycolide (PLGA), polyesters, poly(ortho ester), poly(phosphazine), poly(phosphate ester), polycaprolactones, gelatin, collagen, derivatives thereof, and combinations thereof.  
     
     
         38 . The method of  claim 34 , wherein the therapeutic component and the polymeric component are associated in the form of an implant selected from the group consisting of solid implants, semisolid implants, and viscoelastic implants.  
     
     
         39 . The method of  claim 25 , wherein the alpha 2 adrenergic receptor agonist is provided in an amount to provide a therapeutic effect selected from the group consisting of neuroprotection, reduction in intraocular pressure, and combinations thereof.  
     
     
         40 . The method of  claim 25 , wherein the alpha 2 adrenergic receptor agonist is coupled to a polyethylene glycol.  
     
     
         41 . The method of  claim 25 , wherein the alpha 2 adrenergic receptor agonist has a structure effective in providing substantially equal elimination rates from the anterior chamber of the eye and the posterior segment of the eye.  
     
     
         42 . The method of  claim 25 , wherein the alpha 2 adrenergic receptor agonist has a structure effective in providing a greater enhanced anterior elimination rate relative to a posterior elimination rate.