Stable Aerosolizable Suspensions of Proteins in Ethanol

Abstract

Stable suspensions of a biologically active protein are disclosed that are suited for aerosol delivery to the lungs of a patient in need of treatment, which comprise particles of biologically active protein suspended in ethanol. In a preferred embodiment, the invention describes a stable suspension of insulin useful for aerosol delivery to the lungs of a patient in need of treatment comprising particles of a pharmaceutically effective amount of insulin suspended in ethanol. A method of delivering a therapeutically effective amount of a protein to the respiratory tract of a patient is described which comprises producing an aerosol of a stable liquid suspension of a protein using an electrohydrodynamic spraying means wherein the liquid suspension comprises particles of the protein suspended in ethanol. The stable ethanol suspensions of the invention may optionally contain up to about 20% (V/V) of a pharmaceutically acceptable formulation additive such as glycerol, propylene glycol and polyethylene glycol as well as minor amounts (from about 0.05% to about 5.0% W/V) of a pharmaceutically acceptable excipient.

1 . A stable suspension of a biologically active protein suited for aerosol delivery to the respiratory tract of a patient in need of treatment comprising particles of said protein suspended in ethanol. 
     
     
         2 . A stable suspension according to  claim 1  wherein said ethanol is substantially anhydrous. 
     
     
         3 . A stable suspension according to  claim 1  wherein said ethanol contains less than 5% water. 
     
     
         4 . A stable suspension according to  claim 1  wherein said ethanol contains less than 3% water. 
     
     
         5 . A stable suspension according to  claim 1  wherein said biologically active protein is selected from the group comprising enzymes, antibodies, antigens, hormones and cytokines. 
     
     
         6 . A stable suspension according to  claim 5  wherein said therapeutically active protein is a hormone. 
     
     
         7 . A stable suspension according to  claim 6  wherein said therapeutically active protein is insulin. 
     
     
         8 . A stable suspension according to  claim 5  wherein said therapeutically active protein is a cytokine. 
     
     
         9 . A stable suspension according to  claim 5  wherein said therapeutically active protein is Factor VIII. 
     
     
         10 . A stable suspension according to  claim 1  wherein the particle size of said protein is from about 0.01μ to about 10.0μ. 
     
     
         11 . A stable suspension according to  claim 10  wherein the particle size of said protein is from about 5.0μ to about 10.0μ. 
     
     
         12 . A stable suspension according to  claim 11  wherein the particle size of said protein is from about 0.01μ to about 3.0μ. 
     
     
         13 . A stable suspension according to  claim 1  wherein said suspension contains up to 20% V/V of a formulation additive. 
     
     
         14 . A stable suspension according to  claim 13  wherein said suspension formulation additive is selected from the group consisting of glycerol, propylene glycol and polyethylene glycol. 
     
     
         15 . A stable suspension according to  claim 1  wherein said suspension contains from about 0.5% to about 5.0% of a pharmaceutically acceptable excipient. 
     
     
         16 . A stable suspension of insulin useful for aerosol delivery to the lungs of a patient in need of treatment comprising particles of a pharmaceutically effective amount of insulin suspended in ethanol. 
     
     
         17 . A stable suspension according to  claim 16  wherein said insulin is present in the suspension at a concentration of from about 1.0 mg/ml to about 200.0 mg/ml of suspension. 
     
     
         18 . A stable suspension according to  claim 16  wherein the particle size of said insulin is from about 0.01μ to about 5.0μ. 
     
     
         19 . A stable suspension according to  claim 16  wherein said suspension contains up to 20% V/V of a formulation additive. 
     
     
         20 . A stable suspension according to  claim 19  wherein said suspension formulation additive is selected from the group consisting of glycerol, propylene glycol and polyethylene glycol. 
     
     
         21 . A stable suspension according to  claim 16  wherein said suspension contains from about 0.5% to about 5.0% of a pharmaceutically acceptable excipient. 
     
     
         22 . A method of delivering a therapeutically effective amount of a protein to the respiratory tract of a patient in need of treatment which comprises producing an aerosol of a stable liquid suspension of said protein using an electrostatic spraying means wherein said liquid suspension comprises particles of said protein suspended in ethanol. 
     
     
         23 . A method according to  claim 22  wherein said protein is selected from the group comprising enzymes, antibodies, antigens, hormones and cytokines. 
     
     
         24 . A method according to  claim 23  wherein said therapeutically active protein is a hormone. 
     
     
         25 . A method according to  claim 24  wherein said hormone is insulin. 
     
     
         26 . A method according to  claim 23  wherein said protein is a cytokine. 
     
     
         27 . A method according to  claim 26  wherein said cytokine is Factor VIII. 
     
     
         28 . A method according to  claim 22  wherein the particle size of said protein is from about 0.01μ to about 10.0μ. 
     
     
         29 . A method according to  claim 28  wherein the particle size of said protein is from about 5.0μ to about 10.0μ. 
     
     
         30 . A method according to  claim 29  wherein the particle size of said protein is from about 0.01μ to about 3.0μ. 
     
     
         31 . A stable suspension according to  claim 22  wherein said suspension contains up to 20% V/V of a formulation additive. 
     
     
         32 . A stable suspension according to  claim 31  wherein said suspension formulation additive is selected from the group consisting of glycerol, propylene glycol and polyethylene glycol. 
     
     
         33 . A stable suspension according to  claim 22  wherein said suspension contains from about 0.5% to about 5.0% of a pharmaceutically acceptable excipient.