NON-PROTEIN CLOSTRIDIAL TOXIN COMPOSITIONS
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.