A device for enhanced epithelial permeation of y2 receptor-binding peptides

Abstract

A pharmaceutical device comprising a composition comprising an aqueous solution of PYY(3-36), a cyclodextrin, and a compound selected from phosphatidylcholine or diglyceride, wherein the cyclodextrin and the compound selected from phosphatidylcholine or diglyceride are present in an amount sufficient to enhance epithelial permeation, and wherein the composition is present in a container; and an actuator fluidly connected to the container, wherein the actuator has a tip which defines a passage through which the solution is ejected to produce a spray of the solution.

1 . A pharmaceutical device comprising: 
 a. a composition comprising an aqueous solution of PYY(3-36), a cyclodextrin, and a compound selected from phosphatidylcholine or diglyceride, wherein the cyclodextrin and the compound selected from phosphatidylcholine or diglyceride are present in an amount sufficient to enhance epithelial permeation, and wherein the composition is present in a container;    b. an actuator fluidly connected to the container, wherein the actuator has a tip which defines a passage through which the solution is ejected to produce a spray of the solution.    
   
   
       2 . The device of  claim 1 , wherein the phosphatidylcholine is L-α-phosphatidylcholine didecanoyl (DDPC).  
   
   
       3 . The device of  claim 1 , wherein the cyclodextrin is selected from the group consisting of hydroxypropyl-β-cyclodextrin, sulfobutylether-β-cyclodextrin, and methyl-β-cyclodextrin.  
   
   
       4 . The device of  claim 3 , wherein the cyclodextrin is methyl-β-cyclodextrin.  
   
   
       5 . The device of  claim 1 , wherein the solution has a pH of from about 3 to about 6.  
   
   
       6 . The device of  claim 5 , wherein the pH is 5.0±0.5.  
   
   
       7 . The device of  claim 1 , the composition further comprising a polyol.  
   
   
       8 . The device of  claim 7 , wherein the polyol is selected from the group consisting of sucrose, mannitol, sorbitol, lactose, L-arabinose, D-erythrose, D-ribose, D-xylose, D-mannose, trehalose, D-galactose, lactulose, cellobiose, gentibiose, glycerin and polyethylene glycol.  
   
   
       9 . The device of  claim 7 , wherein the polyol is sorbitol.  
   
   
       10 . The device of  claim 7 , further comprising a chelating agent.  
   
   
       11 . The device of  claim 10 , wherein the chelating agent is ethylene diamine tetraacetic acid (EDTA) or ethylene glycol tetraacetic acid (EGTA).  
   
   
       12 . The device of  claim 10 , wherein the chelating agent is ethylene diamine tetraacetic acid (EDTA).  
   
   
       13 . The device of  claim 7 , further comprising one or more sustained release-enhancing agent(s).  
   
   
       14 . The device of  claim 13 , wherein the sustained release-enhancing agent is polyethylene glycol (PEG).  
   
   
       15 . The device of  claim 1 , wherein the PYY(3-36) is present in solution at a concentration of at least 200 μg/mL.  
   
   
       16 . The device of  claim 1 , wherein the actuator produces a spray having a volume of between 20 and 200 microliters per actuation.  
   
   
       17 . The device of  claim 1 , wherein the spray is comprised of droplets, and wherein less than 10% of the droplets are smaller than 10 microns in size.  
   
   
       18 . The device of  claim 17 , wherein less than 5% of the droplets are smaller than 10 microns in size.  
   
   
       19 . The device of  claim 17 , wherein less than 1% of the droplets are smaller than 10 microns in size.  
   
   
       20 . The device of  claim 17 , wherein the droplets are between 25 and 700 micrometers in size.  
   
   
       21 . The device of  claim 1 , wherein each spray from the actuator contains at least 100 micrograms of PYY(3-36).  
   
   
       22 . The device of  claim 1 , wherein the spray has a spray pattern having major and minor axes of from 10 to 50 mm when measured at a height of from 0.5 cm to 10 cm from the actuator tip.  
   
   
       23 . The device of  claim 1 , wherein the spray is an aerosol with a spray pattern ellipticity ratio of from 1.00 to 1.40 when measured at a height of from 0.5 cm to 10 cm from the actuator tip.  
   
   
       24 . The device of  claim 23 , wherein the ellipticity ratio is from 1.00 to 1.30.  
   
   
       25 . The device of  claim 23 , wherein the ellipticity ratio is from 1.15 to 1.25.