Injectable botulinum toxin formulations

Abstract

This invention provides novel injectable compositions comprising botulinum toxin that may be administered to a subject for various therapeutic, aesthetic and/or cosmetic purposes. The injectable compositions contemplated by the invention exhibit one or more advantages over conventional botulinum toxin formulations, including reduced antigenicity, a reduced tendency to undergo unwanted localized diffusion following injection, increased duration of clinical efficacy or enhanced potency relative, faster onset of clinical efficacy, and/or improved stability.

What is claimed is: 
     
         1 . A kit for providing a sterile injectable botulinum toxin for administration by injection to achieve a therapeutic or cosmetic effect in a subject in need thereof, the kit comprising:
 a botulinum toxin component present in an amount suitable for injection, the   
       botulinum toxin component selected from the group consisting of a botulinum toxin complex, reduced botulinum toxin complex, and botulinum toxin, and
 a positively charged carrier comprising the amino acid sequence RKKRRQRRRG-(K) 15 -GRKKRRQRRR, wherein the positively charged carrier is non-covalently associated with the botulinum toxin component; 
 a pharmaceutically acceptable diluent suitable for injection; and 
 a delivery device for injecting said botulinum toxin component. 
 
     
     
         2 . The kit according to  claim 1 , wherein the botulinum toxin component is obtained from serotypes A, B, C, D, E, F, or G of  C. botulinum.    
     
     
         3 . The kit according to  claim 2 , wherein the botulinum toxin component is a type A botulinum toxin component. 
     
     
         4 . The kit according to  claim 3 , wherein said delivery device is a syringe and a needle. 
     
     
         5 . The kit according to  claim 3 , wherein the botulinum toxin component and the positively charged carrier are pre-formulated in said kit. 
     
     
         6 . The kit according to  claim 5 , wherein the pre-formulated botulinum toxin component and positively charged carrier are provided separately from said pharmaceutically acceptable diluent in said kit. 
     
     
         7 . The kit according to  claim 3 , wherein the botulinum toxin component is provided separately from the positively charged carrier in said kit. 
     
     
         8 . The kit according to  claim 3 , wherein the therapeutic or cosmetic effect results from local muscle paralysis following injection of said botulinum toxin component, said positively charged carrier, and said pharmaceutically acceptable diluent, and wherein said local muscle paralysis lasts longer than local muscle paralysis following injection of the same dose of botulinum toxin units from a formulation of 100 U of type A botulinum toxin with accessory protein, 0.5 mg of human albumin, and 0.9 mg of sodium chloride. 
     
     
         9 . The kit according to  claim 8 , wherein said muscle paralysis lasts approximately twice as long as muscle paralysis following injection of the same dose of botulinum toxin units from a formulation of 100 U of type A botulinum toxin with accessory protein, 0.5 mg of human albumin, and 0.9 mg of sodium chloride. 
     
     
         10 . The kit according to  claim 3 , wherein antibody generation following injection of said botulinum toxin component, said positively charged carrier, and said pharmaceutically acceptable diluent into the subject's body is reduced compared to antibody generation following injection of the same dose of botulinum toxin units from a formulation of 100 U of type A botulinum toxin with accessory protein, 0.5 mg of human albumin, and 0.9 mg of sodium chloride. 
     
     
         11 . The kit according to  claim 3 , wherein the positively charged carrier reduces local diffusion of the botulinum toxin component following injection. 
     
     
         12 . The kit according to  claim 3 , wherein the positively charged carrier stabilizes the botulinum toxin component against degradation. 
     
     
         13 . The kit according to  claim 12 , wherein the positively charged carrier stabilizes the botulinum toxin component against degradation to retain potency after 6 months aging at 4° C. 
     
     
         14 . The kit according to  claim 3 , wherein the therapeutic effect is reducing or enhancing immune response or reducing a symptom associated with a disorder selected from the group consisting of muscular tension, muscular spasm, hemifacial spasm, adult onset spasmodic torticollis, anal fissure, blepharospasm, cerebral palsy, headache, migraine headache, strabismus, temporomandibular joint disorder, neurologic pain, overactive bladder, rhinitis, sinusitis, acne, dystonia, dystonic contractions, cervical dystonia, hyperhidrosis, and hypersecretion of a gland controlled by the cholinergic nervous system. 
     
     
         15 . The kit according to  claim 3 , wherein the cosmetic effect is selected from the group consisting of decreasing the appearance of fine lines and/or wrinkles, adjusting facial appearance in a desirable way, widening the eyes, lifting corners of the mouth, and smoothing lines that fan out from the upper lip. 
     
     
         16 . The kit according to  claim 3 , wherein said botulinum toxin component is present in a single dose amount. 
     
     
         17 . The kit according to  claim 3 , wherein said botulinum toxin component is present in an amount from 10 to 350 U. 
     
     
         18 . The kit according to  claim 17 , wherein said botulinum toxin component is present in an amount from 30 to 250 U. 
     
     
         19 . The kit according to  claim 3 , wherein said botulinum toxin component is present in an amount from 10 to 200 U. 
     
     
         20 . The kit according to  claim 19 , wherein said botulinum toxin component is present in said composition in an amount from 30 to 200 U.