Low immunogenicity corticosteroid compositions

Abstract

Triamcinolone compositions, and methods of using such compositions, useful for injection into the vitreous of human eyes or into a joint are provided. Such compositions can include triamcinolone particles present in a therapeutically effective amount, a viscosity inducing component, and an aqueous carrier component. The compositions have viscosities of at least about 10 cps or about 100 cps at a shear rate of 0.1/second. In a preferred embodiment, the viscosity is in the range of from about 80,000 cps to about 300,000 cps. In a most preferred embodiment, the viscosity is in the range of from about 140,000 cps to about 280,000 cps t a shear rate of 0.1/second at 25° C. The compositions advantageously suspend the triamcinolone particles for prolonged periods of time.

1 . A pharmaceutical composition for treating a posterior ocular condition, the pharmaceutical composition comprising: 
 (a) a plurality of corticosteroid particles mixed with;    (b) a viscous polymer, wherein the pharmaceutical composition has a viscosity of between about 130,000 cps and about 300,000 cps at a shear rate of about 0.1/second at about 25° C., and the pharmaceutical composition can be injected into the vitreous of a human eye through a 25 to 33 gauge needle.    
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the corticosteroid particles have a substantially uniform diameter.  
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein substantially all the corticosteroid particles are embedded within the viscous polymer.  
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the corticosteroid is a triamcinolone.  
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the viscous polymer is a polymeric hyaluronate or a polymeric hyaluronic acid.  
     
     
         6 . A pharmaceutical composition for treating a posterior ocular condition, the composition comprising: 
 (a) a plurality of triamcinolone particles with a substantially uniform diameter, and;    (b) a viscous polymeric hyaluronate or polymeric hyaluronic acid, wherein the pharmaceutical composition has a viscosity of between about 130,000 cps and about 300,000 cps at a shear rate of about 0.1/second at about 25° C. and can be injected into the vitreous of a human eye through a 25 to 33 gauge needle, wherein the triamcinolone particles are mixed with the viscous polymer substantially all the corticosteroid particles are embedded within and coated by the viscous polymeric hyaluronate or a polymeric hyaluronic acid.    
     
     
         7 . A method for treating a posterior ocular condition, the method comprising the step of injecting into the vitreous of a patient's eye with a posterior ocular condition a viscous pharmaceutical composition comprising a plurality of corticosteroid particles mixed into a viscous polymeric matrix, wherein the pharmaceutical composition has a viscosity of between about 130,000 cps and about 300,000 cps at a shear rate of about 0.1/second at about 25° C., such that about one hour after the intravitreal injection only about 10% or less of the corticosteroid particles are present in the vitreous free of the polymeric matrix.  
     
     
         8 . The method of  claim 7 , wherein about one hour after the intravitreal injection only about 5% or less of the corticosteroid particles are present in the vitreous free of the is polymeric matrix.  
     
     
         9 . The method of  claim 7 , wherein about one hour after the intravitreal injection only about 3% or less of the corticosteroid particles are present in the vitreous free of the polymeric matrix.  
     
     
         10 . A process for making an intraocular pharmaceutical composition, the method comprising the step of mixing an aqueous suspension of a plurality of corticosteroid particles and an aqueous solution of a viscous polymeric matrix, so that the resulting pharmaceutical composition has a viscosity of between about 130,000 cps and about 300,000 cps at a shear rate of about 0.1/second at about 25° C.  
     
     
         11 . The process of  claim 10 , wherein the corticosteroid particles have a median particle size of between about 4 microns and about 5 microns.  
     
     
         12 . The process of  claim 10 , wherein the corticosteroid particles have a stable diameter for at least three months after the pharmaceutical has been made and stored for three months in a syringe placed horizontally at about 25° C. at about 60% relative humidity.  
     
     
         13 . The pharmaceutical composition made by the method of  claim 10 .  
     
     
         14 . A pharmaceutical composition for treating an articular pathology, the pharmaceutical composition comprising: 
 (a) a plurality of corticosteroid particles mixed with;    (b) a viscous polymer, wherein the pharmaceutical composition has a viscosity of between about 130,000 cps and about 300,000 cps at a shear rate of about 0.1/second at about 25° C.,    
     
     
         15 . A method for treating an articular pathology, the method comprising the step of is injecting into a joint of a patient with an articular pathology a viscous pharmaceutical composition comprising a plurality of corticosteroid particles mixed into a viscous polymeric matrix, wherein the pharmaceutical composition has a viscosity of between about 130,000 cps and about 300,000 cps at a shear rate of about 0.1/second at about 25° C.