Injectable Depot Compositions and Uses Thereof

Abstract

Injectable depot compositions are provided that include a bioerodible, biocompatible polymer, 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, a thixotropic agent, and a beneficial agent. The solvent comprises an aromatic alcohol, an ester of an aromatic acid, an aromatic ketone, or mixtures thereof. The compositions have substantially improved the shear thinning behavior and reduced injection force, rendering the compositions readily implanted beneath a patients body surface by injection.

1 .- 118 . (canceled) 
     
     
         119 . A composition comprising:
 a bioerodible, biocompatible polymer;   a solvent having a miscibility in water of less than or equal to 7% at 25° C., wherein the solvent is selected from an aromatic alcohol, an ester of an aromatic acid, and mixtures thereof;   a lower alkanol present in an amount of less than 15 weight percent of the combined weight of the solvent and the lower alkanol; and   a beneficial agent.   
     
     
         120 . The composition of  claim 119 , wherein the aromatic alcohol has the structural formula (I)
   Ar-(L) n -OH   
       wherein Ar is aryl or heteroaryl, n is zero or 1, and L is a linking moiety. 
     
     
         121 . The composition of  claim 120 , wherein Ar is monocyclic aryl or heteroaryl, n is 1, and L is lower alkylene optionally containing at least one heteroatom. 
     
     
         122 . The composition of  claim 121 , wherein Ar is monocyclic aryl and L is lower alkylene. 
     
     
         123 . The injectable depot composition of  claim 122 , wherein Ar is phenyl and L is methylene. 
     
     
         124 . The composition of  claim 119 , wherein the lower alkanol comprises ethanol. 
     
     
         125 . The composition of  claim 124 , wherein an amount of the ethanol is greater than or equal to 0.01 weight percent and less than or equal to 15 weight percent of the combined weight of the solvent and the lower alkanol. 
     
     
         126 . The composition of  claim 124 , wherein an amount of the ethanol is greater than or equal to 0.1 weight percent and less than or equal to 5 weight percent of the combined weight of the solvent and the lower alkanol. 
     
     
         127 . The injectable depot composition of  claim 124 , wherein an amount of the ethanol is greater than or equal to 0.5 weight percent and less than or equal to 5 weight percent of the combined weight of the solvent and the lower alkanol. 
     
     
         128 . The composition of  claim 119 , wherein the polymer is selected from polylactides, polyglycolides, polycaprolactones, polyanhydrides, polyamines, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyphosphoesters, polyorthocarbonates, polyphosphazenes, succinates, poly(malic acid), poly(amino acids), polyvinylpyrrolidone, polyethylene glycol, polyhydroxycellulose, chitin, chitosan, hyaluronic acid, and copolymers, terpolymers, and mixtures thereof. 
     
     
         129 . The composition of  claim 119 , wherein the polymer is a lactic acid-based polymer. 
     
     
         130 . The composition of  claim 119 , wherein the polymer is a copolymer of at least two of the following monomers: lactic acid, glycolic acid, and caprolactone. 
     
     
         131 . The composition of  claim 119 , further including at least one of a pore former, a solubility modulator for the beneficial agent, and an osmotic agent. 
     
     
         132 . The composition of  claim 119 , wherein the beneficial agent is selected from a drug, proteins, enzymes, hormones, polynucleotides, nucleoproteins, polysaccharides, glycoproteins, lipoproteins, polypeptides, steroids, analgesics, local anesthetics, antibiotic agents, chemotherapeutic agents, immunosuppressive agents, anti-inflammatory agents, antiproliferative agents, antimitotic agents, angiogenic agents, anticoagulants, fibrinolytic agents, growth factors, antibodies, ocular drugs, and metabolites, analogs, derivatives, and fragments thereof. 
     
     
         133 . The composition of  claim 119 , wherein the beneficial agent is present in an amount of from 0.1 to 50% by weight of the combined amounts of the polymer, the solvent and the beneficial agent. 
     
     
         134 . The composition of  claim 119 , wherein the beneficial agent is dissolved. 
     
     
         135 . The composition of  claim 119 , wherein the beneficial agent comprises particles. 
     
     
         136 . The composition of  claim 119 , wherein the beneficial agent comprises particles having an average particle size of from 0.1 micron to 250 microns.