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 - 20 . (canceled)  
     
     
         21 . A method of producing an ophthalmically therapeutic material comprising: 
 selecting an alpha 2 adrenergic receptor agonist that has a vitreous half-life greater than about 3 hours; and    combining the selected alpha 2 adrenergic receptor agonist with a liquid carrier component or a polymeric component to form a material suitable for administration to an eye, and further comprising at least one step selected from the group consisting of:    administering an alpha 2 adrenergic receptor agonist to an eye of a subject and determining the concentration of the alpha 2 adrenergic receptor agonist in at least one of the vitreous humor and aqueous humor as a function of time; and    administering an alpha 2 adrenergic receptor agonist to an eye of a subject and determining at least one of the vitreous half-life and clearance of the alpha 2 adrenergic receptor agonist from the eye.    
     
     
         22 - 33 . (canceled)  
     
     
         34 . The method of  claim 21 , wherein said agonist is associated with a polymeric 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 35 , 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 agonist 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 34 , 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 34 , wherein the alpha 2 adrenergic receptor agonist is coupled to a polyethylene glycol.  
     
     
         41 . The method of  claim 34 , wherein the alpha 2 adrenergic receptor agonist has a molecular weight greater than the molecular weight of a different alpha 2 adrenergic receptor agonist that is eliminated from the posterior segment of an eye of an individual.  
     
     
         42 . The method of  claim 34 , 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.  
     
     
         43 . The method of  claim 34 , 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.  
     
     
         44 . The method of  claim 34 , wherein the material is suitable for administration to an eye and delivers the alpha 2 adrenergic receptor agonist to a region of the eye selected from the group consisting of the anterior chamber of the eye, the posterior chamber of the eye, or combination thereof.  
     
     
         45 . The method of  claim 34 , wherein the alpha 2 adrenergic receptor agonist is an organic cation having a pKa less than about 7.  
     
     
         46 . The method of  claim 34 , wherein the alpha 2 adrenergic receptor agonist is a non-cationic agent in the interior of an eye.