Pharmaceutical compositions for intraocular administration and methods for fabricating thereof

Abstract

Pharmaceutical compositions for intraocular injection are described, the compositions consisting essentially of a therapeutically effective quantity of an anti-bacterial agent (such as moxifloxacin), a therapeutically effective quantity of an anti-inflammatory agent (such as triamcinolone), at least one pharmaceutically acceptable excipient and a pharmaceutically acceptable carrier. Methods for fabricating the compositions and using them for intraocular injections are also described.

What is claimed is: 
     
         1 . An ophthalmological pharmaceutical composition, comprising:
 (a) a therapeutic component consisting essentially of:
 (a1) a therapeutically effective quantity of an anti-inflammatory agent independently selected from the group consisting of corticosteroids and pharmaceutically acceptable salts, hydrates, solvates, ethers, esters, acetals and ketals thereof; and 
 (a2) a therapeutically effective quantity of non-steroid anti-inflammatory drug that is free of bromfenac; 
   (b) optionally, at least one pharmaceutically acceptable excipient; and   (c) optionally, a pharmaceutically acceptable carrier therefor.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the therapeutic component further comprises a therapeutically effective quantity of a primary anti-bacterial agent independently selected from the group consisting of quinolone, a fluorinated quinolone and pharmaceutically acceptable salts, hydrates, solvates or N-oxides thereof. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the primary anti-bacterial agent is a fluorinated quinolone. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein the fluorinated quinolone is selected from the group consisting of moxifloxacin and gatifloxacin. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the fluorinated quinolone is moxifloxacin. 
     
     
         6 . The pharmaceutical composition of  claim 2 , wherein the primary anti-bacterial agent is a fluorinated quinolone having the chemical structure (A): 
       
         
           
           
               
               
           
         
       
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the corticosteroid is selected from the group consisting of triamcinolone, triamcinolone acetonide, triamcinolone diacetate, triamcinolone benetonide, triamcinolone furetonide, triamcinolone hexacetonide, betamethasone acetate, dexamethasone, fluorometholone, fluocinolone acetonide, prednisone, prednisolone, methylprednisone, corticol, cortisone, fluorocortisone, deoxycorticosterone acetate, aldosterone, budesonide and derivatives, analogs or combinations thereof. 
     
     
         8 . The pharmaceutical composition of  claim 2 , wherein:
 (a) the anti-bacterial agent is moxifloxacin; and   (b) the corticosteroid is triamcinolone or a derivative thereof.   
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the corticosteroid is triamcinolone. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the corticosteroid has the chemical structure (B): 
       
         
           
           
               
               
           
         
       
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the non-steroid anti-inflammatory drug is selected from the group consisting of ketorolac, etodolac, sulindac, diclofenac, aceclofenac, nepafenac, tolmetin, indomethacin, nabumetone, ketoprofen, dexketoprofen, ibuprofen, flurbiprofen, dexibuprofen, fenoprofen, loxoprofen, oxaprozin, naproxen, aspirin, salicylic acid, diflunisal, salsalate, mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamic acid, meloxicam, piroxicam, ternoxicam, droxicam, lornoxicam, isoxicam, celecoxib, rofecoxib, valdecoxib, parecoxib, lumiracoxib, etoricoxib, firocoxib, nimesulide, clonixin, licofelone, pharmaceutically acceptable salts, hydrates, solvates, ethers, esters, acetals and ketals thereof and a combination thereof. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the excipient is a solubilizing and suspending agent selected from the group consisting of non-ionic polyoxyethylene-polyoxypropylene block copolymers. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the excipient is Poloxamer 407®. 
     
     
         14 . The pharmaceutical composition of  claim 1 , wherein the therapeutic component further comprises a therapeutically effective quantity of a secondary anti-bacterial agent selected from the group consisting of vancomycin, teicoplanin, telavancin, decaplanin, ramoplanin, gentamicin, tobramycin, amikacin, cefuroxime and a combination thereof. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the anti-bacterial agent is vancomycin. 
     
     
         16 . The pharmaceutical composition of  claim 2 , wherein the therapeutic component further comprises a therapeutically effective quantity of a secondary anti-bacterial agent selected from the group consisting of vancomycin, teicoplanin, telavancin, decaplanin, ramoplanin, gentamicin, tobramycin, amikacin, cefuroxime and a combination thereof. 
     
     
         17 . The pharmaceutical composition of  claim 16 , wherein the anti-bacterial agent is vancomycin. 
     
     
         18 . An ophthalmological pharmaceutical composition, comprising:
 (a) a therapeutic component consisting essentially of:
 (a1) a therapeutically effective quantity of a primary anti-bacterial agent independently selected from the group consisting of quinolone, a fluorinated quinolone and pharmaceutically acceptable salts, hydrates, solvates or N-oxides thereof; and 
 (a2) a therapeutically effective quantity of non-steroid anti-inflammatory drug that is free of bromfenac; 
   (b) optionally, at least one pharmaceutically acceptable excipient; and   (c) optionally, a pharmaceutically acceptable carrier therefor.   
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein the primary anti-bacterial agent is a fluorinated quinolone. 
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein the fluorinated quinolone is selected from the group consisting of moxifloxacin and gatifloxacin. 
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein the fluorinated quinolone is moxifloxacin. 
     
     
         22 . The pharmaceutical composition of  claim 18 , wherein the primary anti-bacterial agent is a fluorinated quinolone having the chemical structure (A): 
       
         
           
           
               
               
           
         
       
     
     
         23 . The pharmaceutical composition of  claim 18 , wherein the non-steroid anti-inflammatory drug is selected from the group consisting of ketorolac, etodolac, sulindac, diclofenac, aceclofenac, nepafenac, tolmetin, indomethacin, nabumetone, ketoprofen, dexketoprofen, ibuprofen, flurbiprofen, dexibuprofen, fenoprofen, loxoprofen, oxaprozin, naproxen, aspirin, salicylic acid, diflunisal, salsalate, mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamic acid, meloxicam, piroxicam, ternoxicam, droxicam, lornoxicam, isoxicam, celecoxib, rofecoxib, valdecoxib, parecoxib, lumiracoxib, etoricoxib, firocoxib, nimesulide, clonixin, licofelone, pharmaceutically acceptable salts, hydrates, solvates, ethers, esters, acetals and ketals thereof and a combination thereof. 
     
     
         24 . The pharmaceutical composition of  claim 18 , wherein the excipient is a solubilizing and suspending agent selected from the group consisting of non-ionic polyoxyethylene-polyoxypropylene block copolymers. 
     
     
         25 . The pharmaceutical composition of  claim 24 , wherein the excipient is Poloxamer 407®. 
     
     
         26 . The pharmaceutical composition of  claim 18 , wherein the therapeutic component further comprises a therapeutically effective quantity of a secondary anti-bacterial agent selected from the group consisting of vancomycin, teicoplanin, telavancin, decaplanin, ramoplanin, gentamicin, tobramycin, amikacin, cefuroxime and a combination thereof. 
     
     
         27 . The pharmaceutical composition of  claim 26 , wherein the secondary anti-bacterial agent is vancomycin. 
     
     
         28 . An ophthalmological pharmaceutical composition, comprising:
 (a) a therapeutic component consisting essentially of:
 (a1) a therapeutically effective quantity of an anti-inflammatory agent independently selected from the group consisting of corticosteroids and pharmaceutically acceptable salts, hydrates, solvates, ethers, esters, acetals and ketals thereof; and 
 (a2) a secondary anti-bacterial agent selected from the group consisting of vancomycin, teicoplanin, telavancin, decaplanin, ramoplanin, gentamicin, tobramycin, amikacin, cefuroxime and a combination thereof; 
   (b) optionally, at least one pharmaceutically acceptable excipient; and   (c) optionally, a pharmaceutically acceptable carrier therefor.   
     
     
         29 . The pharmaceutical composition of  claim 28 , wherein the secondary anti-bacterial agent is vancomycin. 
     
     
         30 . The pharmaceutical composition of  claim 28 , wherein the corticosteroid is selected from the group consisting of triamcinolone, triamcinolone acetonide, triamcinolone diacetate, triamcinolone benetonide, triamcinolone furetonide, triamcinolone hexacetonide, betamethasone acetate, dexamethasone, fluorometholone, fluocinolone acetonide and a combination thereof. 
     
     
         31 . The pharmaceutical composition of  claim 30 , wherein the corticosteroid is triamcinolone. 
     
     
         32 . The pharmaceutical composition of  claim 28 , wherein the corticosteroid has the chemical structure (B): 
       
         
           
           
               
               
           
         
       
     
     
         33 . A method for treating an ophthalmological disease, condition or pathology in a mammalian subject in need of such treatment comprising delivery to the subject the composition of  claim 1 , wherein the method of delivery is selected from the group consisting of intravitreal injection, intraocular intracameral injection, intra-lesional injection, intra-articular injection, subconjunctival injection, sub-tenon injection, delivery via eye drops, delivery via spray and intra-canalicular delivery, to treat the ophthalmological disease, condition or pathology thereby. 
     
     
         34 . A method for treating an ophthalmological disease, condition or pathology in a mammalian subject in need of such treatment comprising delivery to the subject the composition of  claim 2 , wherein the method of delivery is selected from the group consisting of intravitreal injection, intraocular intracameral injection, intra-lesional injection, intra-articular injection, subconjunctival injection, sub-tenon injection, delivery via eye drops, delivery via spray and intra-canalicular delivery, to treat the ophthalmological disease, condition or pathology thereby. 
     
     
         35 . A method for treating an ophthalmological disease, condition or pathology in a mammalian subject in need of such treatment comprising delivery to the subject the composition of  claim 18 , wherein the method of delivery is selected from the group consisting of intravitreal injection, intraocular intracameral injection, intra-lesional injection, intra-articular injection, subconjunctival injection, sub-tenon injection, delivery via eye drops, delivery via spray and intra-canalicular delivery, to treat the ophthalmological disease, condition or pathology thereby. 
     
     
         36 . A method for treating an ophthalmological disease, condition or pathology in a mammalian subject in need of such treatment comprising delivery to the subject the composition of  claim 28 , wherein the method of delivery is selected from the group consisting of intravitreal injection, intraocular intracameral injection, intra-lesional injection, intra-articular injection, subconjunctival injection, sub-tenon injection, delivery via eye drops, delivery via spray and intra-canalicular delivery, to treat the ophthalmological disease, condition or pathology thereby.