Botulinum toxin formulations

Abstract

The invention provides for the use of a presynaptic neurotoxin (for example a bacterial neurotoxin such as botulinum toxin A) for the manufacture of a medicament for the treatment of cerebral palsy in juvenile patients. The juvenile patients are preferably juveniles of up to 6 years in age.

1 - 16 . (canceled)  
     
     
         17 . A method for making a  botulinum  toxin formulation suitable for use in a child seven years of age or younger comprising the steps of: 
 (a) establishing a culture of an anaerobic bacterium of  Clostridium botulinum;      (b) growing a culture of the  Clostridium botulinum  in a fermenter;    (c) harvesting a  botulinum  toxin type A mixture from the fermenter, wherein the  botulinum  toxin type A harvested comprises; 
 (i) a neurotoxic polypeptide component with 
 (1) a molecular weight of about 150 kilodaltons,  
 (2) a short polypeptide chain of about 50 kD, and  
 (3) a larger polypeptide chain of about 100 kD,  
 (4) the two chains being linked together by a disulphide bridge,  
 
 (ii) a complex comprising 
 (5) non-toxic proteins and  
 (6) haemagglutinins,  
 (7) the complex having a molecular weight of about 900 kD;  
 
   (d) purifying the  botulinum  toxin type A from the fermented mixture;    (e) adding human serum albumin as a stabilizer to the  botulinum  toxin type A;    (f) adding a tonicity adjusting agent, selected from the group consisting of sodium chloride, glycerol and a sugar, to the  botulinum  toxin type A to form a solution;    (g) sterile filtering the solution;    (h) vacuum drying the solution to form a powder;    (i) preparing the powder in a unit dosage form selected from the group consisting of (1) a sterile solution in a vial made by reconstituting the powder with sterile unpreserved normal saline to thereby form a sterile, pyrogen-free aqueous solution or dispersion of a  botulinum  toxin type A, and; (2) a vial or sachet containing a lyophilised powder for reconstitution with a carrier, thereby making a high potency  botulinum  toxin formulation suitable for use in a child seven years of age or younger, the high potency of the  botulinum  toxin formulation being expressed in multiple LD 50  units per nanogram of the formulation.    
     
     
         18 . A high potency  botulinum  toxin formulation made by the method of  claim 17 .  
     
     
         19 . A high potency  botulinum  toxin formulation suitable for use in a child seven years of age or younger comprising: 
 (a) a  botulinum  toxin type A, the  botulinum  toxin type A being made by 
 (i) establishing a culture of an anaerobic bacterium of  Clostridium botulinum;    
 (ii) growing a culture of the  Clostridium botulinum  in a fermenter, and;  
 (iii) harvesting a  botulinum  toxin type A mixture from the fermenter;  
 (iv) purifying the  botulinum  toxin type A from the fermented mixture, wherein the  botulinum  toxin type A comprises;  
 (A) a neurotoxic polypeptide component with 
 (1) a molecular weight of about 150 kilodaltons,  
 (2) a short polypeptide chain of about 50 kD, and  
 (3) a larger polypeptide chain of about 100 kD,  
 (4) the two chains being linked together by a disulphide bridge, and  
 
 (B) a complex comprising 
 (5) non-toxic proteins and  
 (6) haemagglutinins,  
 (7) the complex having a molecular weight of about 900 kD;  
 
   (b) human serum albumin to act as a stabilizer to the  botulinum  toxin type A;    (c) a tonicity adjusting agent, selected from the group consisting of sodium chloride, glycerol and a sugar, thereby making a high potency  botulinum  toxin formulation suitable for use in a child seven years of age or younger, the high potency of the  botulinum  toxin formulation being expressed in multiple LD 50  units per nonogram of the formulation.