Non-protein clostridial toxin compositions

Abstract

Pharmaceutical compositions that stabilize a Clostridial toxin active ingredient are described. The compositions can be liquid or solid compositions, and comprise a surfactant and an antioxidant. In some embodiments, the compositions comprise a surfactant selected from a poloxamer and a polysorbate; an antioxidant selected from methionine, N-acetyl cysteine, ethylenediaminetetraacetic acid and combinations thereof, and, optionally, a tonicity agent and/or a lyoprotector selected from, for example, trehalose, sucrose.

1 - 19 . (canceled) 
     
     
         20 . A solid pharmaceutical composition which is free of protein excipients, the composition comprising:
 (i) a Clostridial botulinum toxin active ingredient;   (ii) a poloxamer surfactant; and   (iii) about 0.01 to 5 wt % methionine;   wherein the composition is suitable for subcutaneous or intramuscular injection after reconstitution with an aqueous carrier; and wherein the solid composition is stable for at least one month at 40° C.   
     
     
         21 . The composition of  claim 20 , wherein the Clostridial botulinum toxin active ingredient is selected from the group consisting of botulinum toxin serotype A (BoNT/A), botulinum toxin serotype B (BoNT/B), and botulinum toxin serotype E (BoNT/E). 
     
     
         22 . The composition of  claim 20 , wherein the Clostridial botulinum toxin active ingredient is botulinum toxin serotype E (BoNT/E). 
     
     
         23 . The composition of  claim 20 , wherein the Clostridial botulinum toxin active ingredient comprises the approximately 150 kDa neurotoxin unassociated with complex proteins. 
     
     
         24 . The composition of  claim 20 , wherein the composition further comprises a salt. 
     
     
         25 . The composition of  claim 24 , wherein the salt comprises NaCl. 
     
     
         26 . The composition of  claim 20 , wherein the poloxamer surfactant comprises poloxamer 188 (P188). 
     
     
         27 . The composition of  claim 20 , wherein the composition further comprises a disaccharide. 
     
     
         28 . The composition of  claim 27 , wherein the disaccharide is selected from sucrose or trehalose. 
     
     
         29 . The composition of  claim 27 , where the disaccharide comprises trehalose. 
     
     
         30 . The composition of  claim 20 , wherein the aqueous carrier comprises a buffer. 
     
     
         31 . The composition of  claim 30 , wherein the buffer comprises histidine buffer. 
     
     
         32 . The composition of  claim 20 , wherein the composition comprises:
 (i) botulinum toxin serotype E (BoNT/E);   (ii) about 0.5 to 8 wt % of a poloxamer surfactant; and   (iii) about 0.01 to 5 wt % methionine.   
     
     
         33 . The composition of  claim 20 , wherein the composition comprises:
 (i) botulinum toxin serotype E (BoNT/E);   (ii) histidine buffer;   (iii) about 0.5 to 8 wt % of a poloxamer surfactant; and   (iv) about 0.01 to 5 wt % methionine.   
     
     
         34 . The composition of  claim 20 , wherein the composition comprises:
 (i) botulinum toxin serotype E (BoNT/E);   (ii) histidine buffer;   (iii) about 0.5 to 8 wt % P188; and   (iv) about 0.01 to 5 wt % methionine.   
     
     
         35 . The composition of  claim 24 , wherein the composition comprises:
 (i) botulinum toxin serotype E (BoNT/E);   (ii) histidine buffer;   (iii) about 0.5 to 8 wt % P188;   (iv) about 0.01 to 5 wt % methionine; and   (v) NaCl.   
     
     
         36 . The composition of  claim 27 , wherein the composition comprises:
 (i) botulinum toxin serotype E (BoNT/E);   (ii) histidine buffer;   (iii) about 0.5 to 8 wt % P188;   (iv) about 0.01 to 5 wt % methionine; and   (v) trehalose.   
     
     
         37 . The composition of  claim 20 , wherein the composition comprises:
 (i) botulinum toxin serotype E (BoNT/E);   (ii) 20 mM histidine buffer;   (iii) about 4 wt % P188;   (iv) about 0.2 wt % methionine;   (v) about 8 wt % trehalose; and   (vi) about 0.2 wt % NaCl.   
     
     
         38 . The composition of  claim 20 , wherein the composition comprises:
 (i) botulinum toxin serotype E (BoNT/E);   (ii) 20 mM histidine buffer;   (iii) about 4 wt % P188;   (iv) about 0.2 wt % methionine;   (v) about 2 wt % trehalose; and   (vi) about 0.2 wt % NaCl.   
     
     
         39 . The composition of  claim 20 , wherein the composition comprises:
 (i) botulinum toxin serotype E (BoNT/E);   (ii) 20 mM histidine buffer;   (iii) about 4 wt % P188;   (iv) about 0.2 wt % methionine;   (v) about 8 wt % trehalose; and   (vi) about 0.6 wt % NaCl.   
     
     
         40 . The composition of  claim 20 , wherein the composition is lyophilized or vacuum dried.