Injectable, Non-Aqueous Suspension with High Concentration of Therapeutic Agent

Abstract

An injectable, nonaqueous suspension including at least one therapeutic agent suspended in a single component vehicle. The single component vehicle is a single amphiphilic material, such as a polyethoxylated castor oil or derivative thereof a polyoxyethylene alkyl ether, a polyoxyethylene sorbitan fatty acid ester, a polyoxyethylene stearate, a block copolymer of polyethylene oxide-polypropylene oxide-polyethylene oxide, a block copolymer of polypropylene oxide-polyethylene oxide-polypropylene oxide, a tetra-functional block copolymer of polyethylene oxide-polypropylene oxide, or a tetra-functional block copolymer of polypropylene oxide-polyethylene oxide. A dosage kit that includes the injectable, nonaqueous suspension and a method of administering the injectable, nonaqueous suspension are also disclosed.

What is claimed is: 
     
         1 . An injectable, nonaqueous suspension comprising at least one therapeutic agent suspended in a single component vehicle having an amphiphilic material. 
     
     
         2 . The injectable, nonaqueous suspension of  claim 1 , wherein the single component vehicle comprises a polyethoxylated castor oil or derivative thereof, a polyoxyethylene alkyl ether, a polyoxyethylene sorbitan fatty acid ester, a polyoxyethylene stearate, a block copolymer of polyethylene oxide-polypropylene oxide-polyethylene oxide, a block copolymer of polypropylene oxide-polyethylene oxide-polypropylene oxide, a tetra-functional block copolymer of polyethylene oxide-polypropylene oxide, or a tetra-functional block copolymer of polypropylene oxide-polyethylene oxide. 
     
     
         3 . The injectable, nonaqueous suspension of  claim 1 , wherein the single component vehicle comprises a reaction product of castor oil with ethylene oxide in a molar ratio of 1 to 35 or a reaction product of castor oil with ethylene oxide in a molar ratio of 1 to 45. 
     
     
         4 . The injectable, nonaqueous suspension of  claim 1 , wherein the at least one therapeutic agent comprises a small molecule, protein, antibody, mimetibody, monoclonal antibody, antibody fragment, peptide, nucleotide, DNA fragment, RNA fragment, plasmid fragment, nucleotide fragment, or mixtures thereof. 
     
     
         5 . The injectable, nonaqueous suspension of  claim 1 , wherein the at least one therapeutic agent is present at a concentration that ranges from greater than or equal to approximately 50 mg/ml to approximately 500 mg/ml. 
     
     
         6 . The injectable, nonaqueous suspension of  claim 1 , wherein the at least one therapeutic agent comprises from approximately 5% by weight of a total weight of the injectable, nonaqueous suspension to approximately 50% by weight of the total weight of the injectable, nonaqueous suspension. 
     
     
         7 . The injectable, nonaqueous suspension of  claim 1 , further comprising at least one antioxidant. 
     
     
         8 . The injectable, nonaqueous suspension of  claim 1 , wherein the suspension has an injection force that is less than or equal to about 50 lbf. 
     
     
         9 . The injectable, nonaqueous suspension of  claim 1 , wherein the single component vehicle comprises a polyethoxylated castor oil or derivative thereof and the at least one therapeutic agent comprises a monoclonal antibody. 
     
     
         10 . A dosage kit comprising a syringe and an injectable, nonaqueous suspension, the injectable, nonaqueous suspension comprising at least one therapeutic agent suspended in a single component vehicle having an amphiphilic material. 
     
     
         11 . The dosage kit of  claim 10 , wherein the single component vehicle comprises a polyethoxylated castor oil or derivative thereof, a polyoxyethylene alkyl ether, a polyoxyethylene sorbitan fatty acid ester, a polyoxyethylene stearate, a block copolymer of polyethylene oxide-polypropylene oxide-polyethylene oxide, a block copolymer of polypropylene oxide-polyethylene oxide-polypropylene oxide, a tetra-functional block copolymer of polyethylene oxide-polypropylene oxide, or a tetra-functional block copolymer of polypropylene oxide-polyethylene oxide. 
     
     
         12 . The dosage kit of  claim 10 , wherein the at least one therapeutic agent comprises a small molecule, protein, antibody, mimetibody, monoclonal antibody, antibody fragment, peptide, nucleotide, DNA fragment, RNA fragment, plasmid fragment, nucleotide fragment, or mixtures thereof. 
     
     
         13 . A method of administering a therapeutic agent, comprising:
 suspending at least one therapeutic agent in a single component amphiphilic vehicle to form an injectable, nonaqueous suspension; and   injecting the injectable, nonaqueous suspension into a patient in need thereof.   
     
     
         14 . The method of  claim 13 , wherein suspending at least one therapeutic agent in a single component vehicle comprises suspending the at least one therapeutic agent in a single component vehicle selected from the group consisting of a polyethoxylated castor oil or derivative thereof, a polyoxyethylene alkyl ether, a polyoxyethylene sorbitan fatty acid ester, a polyoxyethylene stearate, a block copolymer of polyethylene oxide-polypropylene oxide-polyethylene oxide, a block copolymer of polypropylene oxide-polyethylene oxide-polypropylene oxide, a tetra-functional block copolymer of polyethylene oxide-polypropylene oxide, and a tetra-functional block copolymer of polypropylene oxide-polyethylene oxide. 
     
     
         15 . The method of  claim 13 , wherein suspending at least one therapeutic agent in a single component vehicle comprises suspending the at least one therapeutic agent in a reaction product of castor oil with ethylene oxide in a molar ratio of 1 to 35 or in a reaction product of castor oil with ethylene oxide in a molar ratio of 1 to 45. 
     
     
         16 . The method of  claim 13 , wherein suspending at least one therapeutic agent in a single component vehicle comprises suspending a small molecule, protein, antibody, mimetibody, monoclonal antibody, antibody fragment, peptide, nucleotide, DNA fragment, RNA fragment, plasmid fragment, nucleotide fragment, or mixtures thereof in the single component vehicle. 
     
     
         17 . The method of  claim 13 , wherein the at least one therapeutic agent is present at a concentration that ranges from greater than or equal to approximately 50 mg/ml to approximately 500 mg/ml. 
     
     
         18 . The method of  claim 13 , wherein the at least one therapeutic agent comprises from approximately 5% by weight of a total weight of the injectable, nonaqueous suspension to approximately 50% by weight of the total weight of the injectable, nonaqueous suspension. 
     
     
         19 . The method of  claim 13 , further comprising adding at least one antioxidant to the injectable, nonaqueous suspension. 
     
     
         20 . The method of  claim 13 , wherein the single component amphiphilic vehicle comprises a polyethoxylated castor oil or derivative thereof and the at least one therapeutic agent comprises a monoclonal antibody.