Injectable aqueous ophthalmic composition and method of use therefor

Abstract

The present invention is directed to the provision of an ophthalmic composition suitable for intravitreal injection. The composition includes an amount of complexing agent that reacts with one or more endogenous components (e.g., hyaluronic acid) in the eye to form a mass of enhanced viscosity. This mass can aid in creating a desirable release profile of therapeutic agent.

What is claimed is: 
     
         1 : An injectable ophthalmic composition, comprising:
 a therapeutic agent;   complexing agent in the composition at a concentration that is at least 0.01 w/v % but no greater than 10 w/v % of the composition wherein, upon injection into a vitreous humor of an eye of a human, the complexing agent forms a complex with endogenous hyaluronic acid, collagen or both to form a mass of enhanced viscosity within the vitreous humor and wherein the complexing agent is positively charged and the complexing agent is selected from the group consisting of a polyamino acid, a cationic derivatized galactomannan polymer and a quaternary copolymer; and   water;   wherein the mass of enhanced viscosity breaks down in the vitreous humor to release the therapeutic agent and/or the therapeutic agent diffuses out of the mass of is enhanced viscosity over an extended period of time of at least 8 hours and wherein, upon formation, the mass of enhanced viscosity has a viscosity greater than the viscosity of the injectable composition at the time of injection and wherein the composition is contained within a syringe, the syringe having a needle suitable for intravitreal injection.   
     
     
         2 : The composition as in  claim 1  wherein the therapeutic agent is a protein or peptide. 
     
     
         3 : The composition as in  claim 1  wherein the therapeutic agent is hydrophilic. 
     
     
         4 : The composition as in  claim 1  wherein the therapeutic agent is hydrophobic and entrapped as nanoparticles, submicron particles, microparticles or a combination thereof 
     
     
         5 : The composition as in  claim 1  wherein the density of the mass, upon formation, is less than 5% higher or lower than the density of the vitreous fluid. 
     
     
         6 : The composition as in  claim 5  wherein the mass moves no more than 5 millimeters during at least 50% of the extended period of time. 
     
     
         7 : The composition as in  claim 1  wherein the extended period of time is at least 20 days. 
     
     
         8 : The composition as in  claim 1  wherein the composition is free of hyaluronic acid. 
     
     
         9 : An injectable ophthalmic composition, comprising:
 a therapeutic agent;   complexing agent in the composition at a concentration that is at least 0.01 w/v % but no greater than 10 w/v % of the composition wherein, upon injection into a vitreous humor of an eye of a human, the complexing agent forms a complex with endogenous hyaluronic acid, collagen or both to form a mass of enhanced viscosity within the vitreous humor and wherein the complexing agent is positively charged and the complexing agent is selected from the group consisting of a polyamino acid, a cationic derivatized galactomannan polymer and a quaternary copolymer; and   water;   wherein the composition is contained within a syringe, the syringe having a needle is suitable for intravitreal injection and wherein the mass of enhanced viscosity breaks down in the vitreous humor to release the therapeutic agent and/or the therapeutic agent diffuses out of the mass of enhanced viscosity over an extended period of time and wherein the extended time period is at least 20 days and wherein, upon formation, the mass of enhanced viscosity has a viscosity greater than the viscosity of the injectable composition at the time of injection.   
     
     
         10 : The composition as in  claim 9  wherein the therapeutic agent is a protein or peptide. 
     
     
         11 : The composition as in  claim 9  wherein the therapeutic agent is hydrophilic. 
     
     
         12 : The composition as in  claim 9  wherein the therapeutic agent is hydrophobic and entrapped as nanoparticles, submicron particles, microparticles or a combination thereof and wherein the composition is free of hyaluronic acid. 
     
     
         13 : The composition as in  claim 9  wherein the complexing agent is such that the mass forms with a density that enables the mass to remain substantially stationary relative to the eye for a substantial portion of the extended period of time and wherein the substantial portion is at least 50% of the extended period of time and wherein substantially stationary means that a center of the mass moves no more than 5 millimeters during the substantial portion of the extended period of time. 
     
     
         14 : A method or forming and/or administering an intravitreal injection, the method comprising:
 filling a syringe with a composition, the composition including:
 i. a therapeutic agent; 
 ii. an amount of complexing agent sufficient to form a mass of enhanced viscosity within a vitreous humor of an eye of a human upon injection of the composition into the eye; and 
 iii. water; and 
   injecting the composition into an eye of a human with the syringe and allowing the io mass of enhanced viscosity to break down in the vitreous humor to release the therapeutic agent and/or allow the therapeutic agent to diffuses out of the mass of enhanced viscosity over an extended period of time.   
     
     
         15 : A method as in  claim 14  wherein:
 i. the complexing agent is positively charged and is selected from galactomannan polymer, a poly-amino acid, a quaternary ammonium compound, a cellulosic polymer or a combination thereof; 
 ii. the amount of complexing agent is at least 0.01 w/v % but no greater than 10 w/v % of the composition; 
 iii. the complexing agent forms a complex with endogenous hyaluronic acid, collagen or both for forming the mass; and 
 iv. the extended time period is at least 20 days.