Compositions and Methods for Safe Treatment of Rhinitis

Abstract

Methods for treating rhinitis in a subject are provided herein. The methods of the present invention comprise intranasal administration of a topical composition comprising a purified botulinum neurotoxin, a carrier and a viscosity modifier to one or more inner surfaces of the nose. The methods disclosed herein provide alternative methods for delivery of botulinum neurotoxin to the nasal anatomy for the treatment of rhinitis.

1 . A method for treating rhinitis, the method comprising
 intranasally administering a therapeutically effective amount of a topical botulinum toxin composition to a patient in need of treatment; wherein said topical botulinum toxin composition comprises   a purified 150 kDa botulinum neurotoxin isolated from botulinum toxin type A;   a carrier molecule comprising a positively charged backbone with positively charged efficiency groups attached thereto; and   a viscosity modifier in the form of a gel or a solution that forms a gel upon an increase in temperature;   wherein the positively charged backbone comprises a polypeptide; and   a pharmaceutically acceptable diluent;   wherein said intranasal administration provides a dose of the purified botulinum neurotoxin of 250 U to 12,500 U to said patient.   
     
     
         2 - 4 . (canceled) 
     
     
         5 . The method according to  claim 1 , wherein the polypeptide comprises polylysine; and
 wherein the positively charged efficiency groups are selected from the group consisting of -(gly) n1 -(arg) n2  (SEQ ID NO:1) (gly)p-RGRDDRRQRRR-(gly)q (SEQ ID NO:2), (gly)p-YGRKKRRQRRR-(gly)q (SEQ ID NO:3), (gly)p-RKKRRQRRR-(gly)q (SEQ ID NO:4) wherein the subscripts p and q are each independently an integer of from 0 to 20, and wherein n1 is an integer of from 0 to 20 and the subscript n2 is independently an odd integer of from about 5 to about 25.   
     
     
         6 . The method according to  claim 5 , wherein said carrier molecule comprises the amino acid sequence RKKRRQRRRG-(K) 15 -GRKKRRQRRR. 
     
     
         7 . The method according to  claim 6 , wherein the viscosity modifier is selected from the group consisting of poloxamer 188 and poloxamer 407 and combinations thereof. 
     
     
         8 . The method according to  claim 7 , wherein the viscosity modifier agent is poloxamer 407. 
     
     
         9 . The method according to  claim 8 , wherein the poloxamer 407 is present in the botulinum toxin composition at a concentration of 10-25%. 
     
     
         10 . The method according to  claim 9 , wherein the poloxamer 407 is present in the botulinum toxin composition at a concentration of 15-20%. 
     
     
         11 . The method according to  claim 6 , wherein the topical botulinum toxin composition is administered to a patient's inferior turbinates. 
     
     
         12 . The method according  claim 6 , wherein said topical botulinum toxin composition contains botulinum toxin at a concentration in the range of 5,500 to 7,000 U/mL. 
     
     
         13 . The method according to  claim 1 , wherein the concentration of botulinum toxin in the topical botulinum toxin composition is 6,250 U/mL. 
     
     
         14 . The method according to  claim 6 , wherein the topical botulinum toxin composition is applied using an applicator. 
     
     
         15 . The method according to  claim 14 , wherein the applicator is a swab. 
     
     
         16 . The method according to  claim 6 , wherein the rhinitis is selected from the group consisting of infectious rhinitis, non-allergic rhinitis, vasomotor rhinitis, allergic rhinitis, rhinitis medicamentosa, atrophic rhinitis, rhinitis sicca, and polypous rhinitis. 
     
     
         17 . The method according to  claim 16 , wherein the rhinitis is non-allergic rhinitis or vasomotor rhinitis. 
     
     
         18 - 22 . (canceled) 
     
     
         23 . The method according to  claim 12 , wherein said topical botulinum toxin composition is applied using a single intranasal application for a duration of 5 seconds to 60 minutes. 
     
     
         24 . The method according to  claim 23 , wherein said duration is 30 seconds to 45 minutes. 
     
     
         25 . The method according to  claim 24 , wherein said duration is 1 minute to 30 minutes. 
     
     
         26 . The method according to  claim 25 , wherein said duration is 30 minutes. 
     
     
         27 . A method for treating rhinitis, the method comprising
 intranasally administering a therapeutically effective amount of a topical botulinum toxin composition to a patient in need of treatment; wherein said topical botulinum toxin composition comprises   a purified 150 kDa botulinum neurotoxin isolated from botulinum toxin type A;   a carrier molecule comprising the amino acid sequence RKKRRQRRRG-(K) 15 -GRKKRRQRRR; and   poloxamer 407.   
     
     
         28 . A method for treating rhinitis, the method comprising
 intranasally administering a therapeutically effective amount of a topical botulinum toxin composition to a patient in need of treatment; wherein said topical botulinum toxin composition comprises   a purified 150 kDa botulinum neurotoxin isolated from botulinum toxin type A;   a carrier molecule comprising the amino acid sequence RKKRRQRRRG-(K) 15 -GRKKRRQRRR; and   wherein said intranasal administration provides a dose of the purified botulinum neurotoxin of 250 U to 12,500 U to said patient.