Intrapulmonary delivery of polypeptide growth factors and cytokines

Abstract

Polypeptides selected from the group of growth factors and cytokines are administered by intrapulmonary inhalation. Disclosed are novel compositions and devices for effecting the intrapulmonary administration of these polypeptides.

1 . A device for delivering to the blood stream of a patient a therapeutic dose of a polypeptide selected from the group of growth factors or cytokines, said device comprising reservoir means for storing the polypeptide; a therapeutic dosage form of the polypeptide disposed in the reservoir means; dispersing means for forming in a gas a suspension of particles comprising the polypeptide wherein the size of the particles is sufficiently small to permit their penetration into the alveoli of the patient's lungs upon inhalation; means for transporting the polypeptide to the dispersing means and means for delivering the particle suspension to the alveoli of the patient's lungs.  
     
     
         2 . The device of  claim 1  wherein the dispersing means is capable of producing particles having a size of about from 0.5 mm to 4 mm.  
     
     
         3 . The device of  claim 1  wherein the polypeptide is somatropin, somatrem, interleukin 1, interleukin 2, tumor necrosis factor-a, tumor necrosis factor-b, a combination of tumor necrosis factor-a or tumor necrosis factor-b plus an interferon; or a combination of an interferon and interleukin-2.  
     
     
         4 . The device of  claim 1  wherein the dispersing means is a means for hydraulic atomization or means for ultrasonic dispersion.  
     
     
         5 . The device of  claim 1  wherein the reservoir means is capable of containing an aqueous solution of the polypeptide.  
     
     
         6 . The device of  claim 1  wherein the reservoir means is capable of containing a powder comprising the polypeptide suspended in a dry fluorocarbon.  
     
     
         7 . The device of  claim 1  wherein the means for delivering the suspension to the alveoli is a mouthpiece for sealably engaging the oral cavity.  
     
     
         8 . A method for delivering to the blood stream of a patient a therapeutic dose of a polypeptide selected from the group of growth factors and cytokines comprising delivering a therapeutically effective dose of the polypeptide into the lungs of the patient.  
     
     
         9 . The method of  claim 8  wherein the polypeptide is somatropin, somatrem, interleukin 1, interleukin 2, tumor necrosis factor-a, tumor necrosis factor-b, a combination of tumor necrosis factor-a or tumor necrosis factor-b plus an interferon; or a combination of an interferon and interleukin-2.  
     
     
         10 . The method of  claim 8  wherein the polypeptide is unaccompanied by an absorption enhancing agent.  
     
     
         11 . The method of  claim 8  wherein the polypeptide is present in particulates having a mean average diameter of about from 0.5 to 4 mm.  
     
     
         12 . The method of  claim 11  wherein the particulates are an aerosol of an aqueous solution of the polypeptide.  
     
     
         13 . The method of  claim 8  wherein the dose is delivered into the alveoli of the lungs without substantial contact with the nasal passages.  
     
     
         14 . A dispersion of polypeptide containing particles wherein greater than about 15% of the particles have a mean average diameter of about from 0.5 to 4 mm and wherein the polypeptide is selected from a therapeutically effective dosage of a growth factor or cytokine.  
     
     
         15 . The dispersion of  claim 14  wherein the particles contain an aqueous solution of the polypeptide.  
     
     
         16 . The dispersion of  claim 15  wherein the dispersion is free of ether, antigens, histamines, zinc oxide, methacholine, amphophilic steroids, chelating agents, bile salts or water-absorbing water-insoluble polymers in amounts sufficient to