Injection vehicle for polymer-based formulations

Abstract

The invention provides injection vehicles suitable for administering particulate suspensions, such as polymer-based formulations, as well as associated pharmaceutical formulations, articles of manufacture, and kits. Other aspects of the invention included methods for producing and administering pharmaceutical formulations. The injection vehicles of the invention are superior to conventional injection vehicles in that they include a pseudoplastic composition that improves injectability, which facilitates delivery of the desired dose. The injection vehicles of the invention also allow the use of smaller-bore needles than are usually necessary to inject polymer-based formulations, reducing the pain associated with injection of such formulations.

1 . An injection vehicle comprising hyaluronic acid or a derivative thereof at a concentration of about 0.01 to about 0.8 percent by volume. 
     
     
         2 . The injection vehicle of  claim 1 , wherein the injection vehicle comprises hyaluronic acid. 
     
     
         3 . The injection vehicle of  claim 1 , wherein the hyaluronic acid or derivative thereof is dissolved in physiological saline. 
     
     
         4 . A pharmaceutical formulation comprising:
 (a) an effective amount of a biologically active agent in particulate form or coated on, dispersed within, or accompanied by particles; and   (b) an injection vehicle comprising hyaluronic acid or a derivative thereof.   
     
     
         5 . The pharmaceutical formulation of  claim 4  wherein the biologically active agent dispersed within particles comprising a biocompatible polymeric matrix. 
     
     
         6 . The pharmaceutical formulation of  claim 5 , wherein the injection vehicle comprises hyaluronic acid. 
     
     
         7 . The pharmaceutical formulation of  claim 6 , wherein the concentration of hyaluronic acid is between about 0.01 and about 0.8 percent weight per volume. 
     
     
         8 . The pharmaceutical formulation of  claim 6 , wherein the hyaluronic acid is dissolved in physiological saline. 
     
     
         9 . The pharmaceutical formulation of  claim 6 , wherein the polymer matrix comprises a polymer selected from the group consisting of a biodegradable polymer, a non-biodegradable polymer, a mixture of biodegradable and non-biodegradable polymers, and a copolymer comprising biodegradable and non-biodegradable units. 
     
     
         10 . The pharmaceutical formulation of  claim 6 , wherein the polymeric matrix comprises a polymer selected from the group consisting of blocked polymers, unblocked polymers, and mixtures thereof. 
     
     
         11 . The pharmaceutical formulation of  claim 6 , wherein the polymeric matrix comprises a polymer selected from the group consisting of a poly(glycolide); a poly(lactide-co-glycolide); a poly(lactic acid); a poly(glycolic acid); a poly(lactic acid-co-glycolic acid); a polyanhydride; a polyorthoester; a polyetherester; a polycaprolactone; a polyesteramide; a block copolymer of polyethylene glycol and lactide or glycolide; and a blend or copolymer thereof. 
     
     
         12 . The pharmaceutical formulation of  claim 11 , wherein the polymer is a poly(lactide-co-glycolide) polymer. 
     
     
         13 . The pharmaceutical formulation of  claim 6 , wherein the biologically active agent is a polypeptide. 
     
     
         14 . The pharmaceutical formulation of  claim 11 , wherein the polypeptide is selected from the group consisting of a growth hormone, a hepatocyte growth factor (HGF), a vascular endothelial growth factor (VEGF), an anti-vascular endothelial growth factor Fab (anti-VEGF Fab), a glucagon-like peptide I (GLP-I), a nerve growth factor, and an insulin-like growth factor. 
     
     
         15 . The pharmaceutical formulation of  claim 6 , wherein the concentration of the polymeric matrix comprising the biologically active agent is between at least about 1 mg/mL to about 500 mg/mL of formulation. 
     
     
         16 . The pharmaceutical formulation of  claim 15 , wherein the concentration of the polymeric matrix comprising the biologically active agent is between at least about 1 mg/mL to about 300 mg/mL of formulation. 
     
     
         17 . A pharmaceutical formulation comprising:
 (a) particles comprising a biocompatible polymeric matrix comprising a poly(lactide-co-glycolide) polymer;   (b) an effective amount of a biologically active polypeptide dispersed within the polymeric matrix; and   (c) an injection vehicle comprising hyaluronic acid or a derivative thereof.   
     
     
         18 . A method for producing a pharmaceutical formulation comprising:
 adding an effective amount of a biologically active agent in particulate form or coated on, dispersed within, or accompanied by particles   to an injection vehicle comprising hyaluronic acid or a derivative thereof.   
     
     
         19 . The method of  claim 18  wherein the injection vehicle comprises hyaluronic acid. 
     
     
         20 . A method for administering a pharmaceutical formulation of  claim 17  comprising injecting the pharmaceutical formulation through a 23-gauge or smaller needle.