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.

What is claimed is: 
     
         1 . A method for treating rhinitis, the method comprising
 intranasally administering a topical botulinum toxin composition to a patient in need of treatment; wherein said topical botulinum toxin composition comprises   a purified botulinum neurotoxin;   a carrier molecule comprising a positively charged backbone with positively charged efficiency groups attached thereto; and   a viscosity modifier.   
     
     
         2 . The method according to  claim 1 , wherein the purified botulinum neurotoxin is isolated from a botulinum serotype selected from the group consisting of botulinum toxin type A, B, C1, D, E, F, and G. 
     
     
         3 . The method according to  claim 1 , wherein the purified botulinum neurotoxin is isolated from botulinum toxin type A. 
     
     
         4 . The method according to  claim 1 , wherein the positively charged backbone comprises a polypeptide. 
     
     
         5 . The method according to  claim 4 , wherein the polypeptide comprises polylysine. 
     
     
         6 . The method according to  claim 1  or  4 , where the positively charged efficiency groups are selected from the group consisting of -(gly) n1 -(arg) n2 , (gly)p-RGRDDRRQRRR-(gly)q, (gly)p-YGRKKRRQRRR-(gly)q, (gly)p-RKKRRQRRR-(gly)q 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. 
     
     
         7 . The method according to  claim 1 , wherein the viscosity modifier is selected from the group consisting of polyoxyethylene glycol alkyl ethers, polyoxypropylene glycol alkyl ethers, glucoside alkyl ethers, polyoxyethylene glycol octylphenol ethers, polyoxyethylene glycol alkylphenol ethers, glycerol alkyl esters, polyoxyethylene glycol sorbitan alkyl esters, sorbitan alkyl esters, dodecyldimethylamine oxide, block copolymers of polyethylene glycol and polypropylene glycol (polyoxamers) 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 1 , wherein the topical botulinum toxin composition is administered to a patient's inferior turbinates. 
     
     
         12 . The method according  claim 1 , wherein said topical botulinum toxin composition contains botulinum toxin at a concentration in the range of 1,000 U/mL to 20,000 U/mL. 
     
     
         13 . The method according to  claim 1 , wherein the concentration of botulinum toxin in the topical botulinum toxin composition is 5,500 U/mL, 5,750 U/mL, 6,000 U/mL, 6,250 U/mL, 6,500 U/mL, 6,750 U/mL or 7,000 U/mL. 
     
     
         14 . The method according to  claim 1 , wherein the topical botulinum toxin is applied using an applicator. 
     
     
         15 . The method according to  claim 14 , wherein the applicator is a swab. 
     
     
         16 . The method according to  claim 1 , wherein the rhinitis selected from the group consisting of infectious 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 vasomotor rhinitis. 
     
     
         18 . The method according to  claim 1 , wherein the purified botulinum neurotoxin is 10-fold to 90-fold less toxic with respect to oral ingestion by test animals than botulinum toxin complexed with native accessory proteins expressed by  C. botulinum.    
     
     
         19 . The method according to  claim 1 , wherein the purified botulinum neurotoxin is 50-fold to 95-fold less toxic with respect to oral ingestion by test animals than botulinum toxin complexed with native accessory proteins expressed by  C. botulinum.    
     
     
         20 . The method according to  claim 1 , wherein the purified botulinum neurotoxin is 30-fold less toxic with respect to oral ingestion by test animals than botulinum toxin complexed with native accessory proteins expressed by  C. botulinum.    
     
     
         21 . The method according to  claims 18 - 20 , wherein the test animals are guinea pigs. 
     
     
         22 . The method according to  claims 18 - 20 , wherein the test animals are rats.