Animal protein-free pharmaceutical compositions

Abstract

Animal protein-free, solid-form Clostridial toxin pharmaceutical compositions comprising a Clostridial toxin active ingredient and at least two excipients.

1 - 2 . (canceled) 
     
     
         3 . A method to stabilize a Clostridial neurotoxin, comprising:
 providing an aqueous solution comprising a Clostridial neurotoxin and a non-mammalian protein excipient; and   compounding the solution with one or more additional non-protein excipients to provide a formulation comprising the neurotoxin in stable form.   
     
     
         4 . The method of  claim 3 , wherein compounding comprises adding the one or more additional non-protein excipients to water to form a solution and adding the aqueous solution thereto. 
     
     
         5 . A powder pharmaceutical composition, comprising:
 a  botulinum  toxin, wherein the  botulinum  toxin is a type A serotype;   a surfactant;   at least one disaccharide selected from the group consisting of sucrose and trehalose; and   a buffer sufficient to maintain a pH of from about 5 to about 7.3 upon reconstitution with sterile normal saline or water;   wherein the composition is suitable for intramuscular or subcutaneous injection following reconstitution with sterile normal saline or water,   wherein the composition is animal protein free, and   wherein the composition retains at least about 75% of the theoretical maximum potency of the  botulinum  toxin following storage as a powder for three months at room temperature.   
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the pharmaceutical composition is produced by lyophilization or vacuum-drying. 
     
     
         7 . The pharmaceutical composition of  claim 5 , wherein the  botulinum  toxin has a molecular weight of about 150 kD. 
     
     
         8 . The pharmaceutical composition of  claim 5 , wherein the surfactant is poloxamer 188. 
     
     
         9 . The pharmaceutical composition of  claim 5 , wherein the disaccharide is sucrose. 
     
     
         10 . The pharmaceutical composition of  claim 5 , wherein the buffer is citrate buffer. 
     
     
         11 . The pharmaceutical composition of  claim 5 , wherein the buffer is an amino acid buffer. 
     
     
         12 . The pharmaceutical composition of  claim 5 , wherein the room temperature is about 20° C. 
     
     
         13 . The pharmaceutical composition of  claim 5 , wherein the pH is from about 5.5 to about 6.5. 
     
     
         14 . The pharmaceutical composition of  claim 5 , wherein the disaccharide is trehalose. 
     
     
         15 . The pharmaceutical composition of  claim 5 , wherein the buffer is a phosphate buffer. 
     
     
         16 . The pharmaceutical composition of  claim 5 , wherein the disaccharide is present in an amount of about 5 mg to about 250 mg for each about 100 units of the  botulinum  toxin. 
     
     
         17 . The pharmaceutical composition of  claim 5 , comprising about 100 units to about 200 units of the  botulinum  toxin. 
     
     
         18 . A powder pharmaceutical composition, comprising:
 a 150 kD  botulinum  toxin, wherein the  botulinum  toxin is a serotype A;   a surfactant;   about 5 mg to about 250 mg of sucrose or trehalose for each about 100 units of the  botulinum  toxin; and   a buffer sufficient to maintain a pH of from about 5.5 to about 6.5 upon reconstitution with sterile normal saline or water;   wherein the composition is suitable for intramuscular or subcutaneous injection following reconstitution with sterile normal saline or water,   wherein the composition is animal protein free, and   wherein the composition retains at least about 75% of the theoretical maximum potency of the  botulinum  toxin following storage as a powder for three months at room temperature.   
     
     
         19 . The pharmaceutical composition of  claim 18 , comprising about 100 units to about 200 units of the  botulinum  toxin. 
     
     
         20 . The pharmaceutical composition of  claim 18 , wherein the buffer is a citrate or a phosphate buffer. 
     
     
         21 . The pharmaceutical composition of  claim 18 , wherein the surfactant is poloxamer 188. 
     
     
         22 . The pharmaceutical composition of  claim 18 , wherein the room temperature is from about 20° C.