Biodegradable drug delivery compositions

Abstract

A biodegradable drug delivery compositions comprising a triblock copolymer containing a polyester and a polyethylene glycol and a diblock copolymer containing a polyester and an end-capped polyethylene glycol, as well as a pharmaceutically active principle is disclosed.

1 . (canceled) 
     
     
         2 . An injectable biodegradable drug delivery composition comprising:
 (a) a biodegradable triblock copolymer having the formula:
   polylactic acid v -poly(ethylene glycol) w -polylactic acid x    
   wherein v and x are the number of repeat units ranging from 24 to 682 and w is the number of repeat units ranging from 4 to 273 and v=x or v≠x;   (b) a biodegradable diblock copolymer having the formula:
   methoxy poly(ethylene glycol) y -polylactic acid z    
   wherein y and z are the number of repeat units y ranging from 3 to 45 and z ranging from 7 to 327, wherein the ratio of the biodegradable triblock copolymer of (a) and the biodegradable diblock copolymer of (b) is 1:3 to 1:8 or 1:1 to 1:19 or 3:2 to 1:19 in said biodegradable drug composition; and   (c) at least one pharmaceutically active principle.   
     
     
         3 . An injectable biodegradable drug delivery composition comprising:
 (a) a biodegradable triblock copolymer present in an amount of 3.0% to 45% (w %/w %) of the total composition having the formula:
   polylactic acid v -poly(ethylene glycol) w -polylactic acid x    
   wherein v and x are the number of repeat units ranging from 24 to 682 and w is the number of repeat units ranging from 4 to 273 v and x being lactyl or lactoyl repeat units and w being ethylene oxide repeat units and v=x or v≠x; (b) a biodegradable diblock copolymer present in an amount of 8.0% to 50% (w %/w %) of the total composition having the formula:
   methoxy poly(ethylene glycol) y -polylactic acid z    
   wherein y and z are the number of repeat units y ranging from 3 to 45 and z ranging from 7 to 327, y being the number of ethylene oxide repeat units and z the number of lactyl or lactoyl repeat units wherein the ratio of the biodegradable triblock copolymer of (a) and the biodegradable diblock copolymer of (b) is 1:3 to 1:8 or 1:1 to 1:19 or 3:2 to 1:19 in said biodegradable drug composition, which is insoluble in water; and (c) at least one pharmaceutically active principle present in an amount of 1% to 20% (w %/w %) of the total composition.   
     
     
         4 . The injectable biodegradable drug delivery composition according to  claim 2 , wherein said composition forms an implant when injected into the body. 
     
     
         5 . The injectable biodegradable drug composition according to  claim 2 , wherein the ratio of the biodegradable triblock copolymer of (a) and the biodegradable diblock copolymer of (b) is selected from the group of 1:1, 1:2,1:3, 1:4 and 1:5. 
     
     
         6 . The injectable biodegradable drug delivery composition according to  claim 2 , wherein the size of the polyethylene glycol chain ranges from 200 Da to 12 kDa or 194 Da to 12 kDa and the size of the methoxy polyethylene glycol chain ranges from 100 Da to 2 kDa or 164 Da to 2 kDA. 
     
     
         7 . The injectable biodegradable drug delivery composition according  claim 2 , further comprising a pharmaceutically acceptable vehicle. 
     
     
         8 . The biodegradable drug delivery composition according to  claim 2 , wherein the pharmaceutically active principle is present in an amount of 1% to 20% (w %/w %) of the total composition. 
     
     
         9 . The injectable biodegradable drug delivery composition according to  claim 2 , wherein the copolymers are present in an amount of 20% to 50% (w %/w %) of the total composition. 
     
     
         10 . The injectable biodegradable drug delivery composition according to  claim 2 , wherein the triblock copolymer is present in an amount of 3.0% to 45% (w %/w %) of the total composition. 
     
     
         11 . The injectable biodegradable drug delivery composition according to  claim 2 , wherein the diblock copolymer is present in an amount of 8.0% to 50% (w %/w %) of the total composition. 
     
     
         12 . The injectable biodegradable drug delivery composition according to  claim 2 , wherein the polylactic repeat unit to ethylene oxide molar ratio in the composition is between 0.5 to 3.5 or 0.5 to 22.3 in the triblock copolymer and 2 to 6 or 0.8 to 13 in the diblock copolymer. 
     
     
         13 . The injectable biodegradable drug delivery composition according to  claim 2 , further comprising an organic solvent selected from the group of: benzyl alcohol, benzyl benzoate, diethylene glycol dimethyl ether (Diglyme), diethylene glycol monoethyl ether (DEGMEE), dimethyl isosorbide (DMI), dimethyl sulfoxide (DMSO), ethyl acetate, ethyl benzoate, ethyl lactate, ethylene glycol monoethyl ether acetate, glycerol formal, methyl ethyl ketone, methyl isobutyl ketone, N-ethyl-2-pyrrolidone, N-methyl-2-pyrrolidinone (NMP), pyrrolidone-2, tetraglycol, triacetin, tributyrin, tripropionin, or triethylene glycol dimethyl ether (triglyme) and mixtures thereof. 
     
     
         14 . The injectable biodegradable drug delivery according to  claim 13 , wherein the organic solvent is present in an amount of 40% to 74% (w %/w %) of the total composition. 
     
     
         15 . An injectable biodegradable drug delivery composition comprising:
 (a) a biodegradable triblock copolymer having the formula:
   polylactic acid v -poly(ethylene glycol) w -polylactic acid x    
   wherein v and x are the number of repeat units ranging from 24 to 682 and w is the number of repeat units ranging from 4 to 273 and v=x or v≠x;   (b) a biodegradable diblock copolymer having the formula:
   methoxy polyethylene glycol) y -polylactic acid z    
   wherein y and z are the number of repeat units y ranging from 3 to 45 and z ranging from 7 to 327, wherein the ratio of the biodegradable triblock copolymer of (a) and the biodegradable diblock copolymer of (b) is 1:3 to 1:8 or 1:1 to 1:19 or 3:2 to 1:19 in said biodegradable drug composition;   (c) an organic solvent; and   (d) at least one pharmaceutically active principle.   
     
     
         16 . An injectable biodegradable drug delivery composition comprising:
 (a) a biodegradable triblock copolymer having the formula:
   polylactic acid v -poly(ethylene glycol) w -polylactic acid x    
   wherein v and x are the number of repeat units ranging from 24 to 682 and w is the number of repeat units ranging from 4 to 273 and v=x or v≠x;   (b) a biodegradable diblock copolymer having the formula:
   methoxy poly(ethylene glycol) y -polylactic acid z    
   wherein y and z are the number of repeat units y ranging from 3 to 45 and z ranging from 7 to 327, wherein the ratio of the biodegradable triblock copolymer of (a) and the biodegradable diblock copolymer of (b) is 1:3 to 1:8 or 1:1 to 1:19 or 3:2 to 1:19 in said biodegradable drug composition;   (c) dimethyl sulfoxide; and   (d) at least one pharmaceutically active principle.   
     
     
         17 . A biodegradable drug delivery composition, which upon injection the organic solvent diffuses away from the formulation and the remaining copolymers form a solid degradable implant comprising:
 (a) a biodegradable triblock copolymer having the formula:
   polylactic acid v -poly(ethylene glycol) w -polylactic acid x    
   wherein v and x are the number of repeat units ranging from 24 to 682 and w is the number of repeat units ranging from 4 to 273 and v=x or v≠x;   (b) a biodegradable diblock copolymer having the formula:
   methoxy poly(ethylene glycol) y -polylactic acid z    
   wherein y and z are the number of repeat units y ranging from 3 to 45 and z ranging from 7 to 327, wherein the ratio of the biodegradable triblock copolymer of (a) and the biodegradable diblock copolymer of (b) is 1:3 to 1:8 or 1:1 to 1:19 or 3:2 to 1:19 in said biodegradable drug composition;   (c) an organic solvent; and   (d) at least one pharmaceutically active principle, wherein said biodegradable drug delivery composition is an injectable composition.   
     
     
         18 . The biodegradable drug composition according to  claim 16 , wherein said organic solvent is selected from the group of benzyl alcohol, benzyl benzoate, dimethyl isosorbide (DMI), dimethyl sulfoxide (DMSO), ethyl acetate, ethyl benzoate, ethyl lactate, glycerol formal, methyl ethyl ketone, methyl isobutyl ketone, N-ethyl-2-pyrrolidone, N-methyl-2-pyrrolidinone (NMP), pyrrolidone-2, tetraglycol, triacetin, tributyrin, tripropionin and mixtures thereof. 
     
     
         19 . The biodegradable drug composition according to  claim 17 , wherein said organic solvent is selected from the group of benzyl alcohol, benzyl benzoate, dimethyl isosorbide (DMI), dimethyl sulfoxide (DMSO), ethyl acetate, ethyl benzoate, ethyl lactate, glycerol formal, methyl ethyl ketone, methyl isobutyl ketone, N-ethyl-2-pyrrolidone, N-methyl-2-pyrrolidinone (NMP), pyrrolidone-2, triacetin, tributyrin, tripropionin and mixtures thereof. 
     
     
         20 . A method to administer in animals a biodegradable drug delivery composition comprising injecting in said animal said biodegradable drug delivery composition according to  claim 15 , wherein upon injection the organic solvent diffuses away from the formulation and the remaining copolymers form a solid degradable implant.