Injectable multimodal polymer depot compositions and uses thereof

Abstract

Injectable depot compositions are provided that include a polymer matrix having a plurality of bioerodible, biocompatible polymers wherein each polymer of the plurality of polymers has a specified weight average molecular weight; and the polymer matrix has a broad molecular weight distribution of the plurality of polymers; a solvent having a miscibility in water of less than or equal to 7 wt. % at 25° C., in an amount effective to plasticize the polymer and form a gel therewith; and a beneficial agent. The compositions are have substantially improved the shear thinning behavior and reduced injection force, rendering the compositions readily implanted beneath a patient's body surface by injection.

1 .- 84 . (canceled) 
     
     
         85 . A composition comprising:
 (a) a polymer matrix comprising a plurality of polymers, wherein a first of said plurality of polymers is a low molecular weight (LMW) polymer having a weight average molecular weight ranging from about 3000 to about 10,000 and a second is a high molecular weight (HMW) polymer having a weight average molecular weight of greater than about 30,000;   (b) a solvent having a miscibility in water of less than or equal to 7% at 25° C.; and   (c) a beneficial agent.   
     
     
         86 . The composition of  claim 85 , further comprising a medium molecular weight (MMW) polymer having a weight average molecular weight ranging from 10,000 to 30,000. 
     
     
         87 . The composition of  claim 85 , wherein the polymer matrix comprises about 20 wt % to about 90 wt % of the low molecular weight (LMW) polymer. 
     
     
         88 . The composition of  claim 85 , wherein each polymer comprises a lactic acid-based polymer. 
     
     
         89 . The composition of  claim 85 , wherein each polymer is a copolymer of lactic acid and glycolic acid. 
     
     
         90 . The composition of  claim 85 , comprising about 5 wt % to about 90 wt % of the polymers. 
     
     
         91 . The composition of  claim 85 , comprising about 25 wt % to about 80 wt % of the polymers. 
     
     
         92 . The composition of  claim 85 , wherein the solvent is selected from aromatic alcohol, ester of aromatic acid, aromatic ketone, and mixtures thereof. 
     
     
         93 . The composition of  claim 85 , wherein the solvent comprises aromatic alcohol. 
     
     
         94 . The composition of  claim 85 , wherein the solvent is present in an amount effective to plasticize the plurality of polymers and form a gel therewith. 
     
     
         95 . The composition of  claim 85 , wherein the solvent has a miscibility in water of less than or equal to 5 wt % at 25° C. 
     
     
         96 . The composition of  claim 85 , wherein the solvent has a miscibility in water of less than or equal to 1 wt % at 25° C. 
     
     
         97 . The composition of  claim 85 , wherein the solvent is an aromatic alcohol that has the structural formula (I)
   Ar-(L) n -OH  (I)
   in which Ar is a substituted or unsubstituted aryl or heteroaryl group, n is zero or 1, and L is a linking moiety.   
     
     
         98 . The composition of  claim 97 , wherein Ar is monocyclic aryl or heteroaryl, n is 1, and L is lower alkylene optionally containing at least one heteroatom. 
     
     
         99 . The composition of  claim 97 , wherein Ar is monocyclic aryl and L is lower alkylene. 
     
     
         100 . The composition of  claim 97 , wherein Ar is phenyl and L is methylene. 
     
     
         101 . The composition of  claim 85 , wherein the solvent comprises at least one of lower alkyl ester and aralkyl ester of benzoic acid. 
     
     
         102 . The composition of  claim 85 , wherein the solvent comprises at least one of benzyl benzoate and ethyl benzoate. 
     
     
         103 . The composition of  claim 85 , wherein the solvent is a mixture of an aromatic alcohol and an ester of an aromatic acid. 
     
     
         104 . The composition of  claim 85 , wherein the solvent is selected from triacetin, diacetin, tributyrin, triethyl citrate, tributyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, triethylglycerides, triethyl phosphate, diethyl phthalate, diethyl tartrate, mineral oil, polybutene, silicone fluid, glycerin, ethylene glycol, polyethylene glycol, octanol, ethyl lactate, propylene glycol, propylene carbonate, ethylene carbonate, butyrolactone, ethylene oxide, propylene oxide, N-methyl-2-pyrrolidone, 2-pyrrolidone, glycerol formal, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decylmethylsulfoxide, oleic acid, and 1-dodecylazacyclo-heptan-2-one, and mixtures thereof.