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. A stable solid pharmaceutical composition which is free of animal 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.
2. The composition of claim 1 , wherein the Clostridial botulinum toxin active ingredient is botulinum toxin serotype E (BoNT/E).
3. The composition of claim 1 , wherein the Clostridial botulinum toxin active ingredient comprises the approximately 150 kDa neurotoxin unassociated with complex proteins.
4. The composition of claim 1 , wherein the composition further comprises a salt.
5. The composition of claim 4 , wherein the salt comprises NaCl.
6. The composition of claim 1 , wherein the poloxamer surfactant comprises poloxamer 188.
7. The composition of claim 1 , wherein the composition further comprises a disaccharide.
8. The composition of claim 7 , wherein the disaccharide is selected from sucrose or trehalose.
9. The composition of claim 7 , where the disaccharide comprises trehalose.
10. The composition of claim 1 , wherein the aqueous carrier comprises a buffer.
11. The composition of claim 10 , wherein the buffer comprises histidine buffer.
12. The composition of claim 1 , 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.
13. The composition of claim 1 , 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.
14. The composition of claim 1 , wherein the composition comprises:
(i) botulinum toxin serotype E (BoNT/E);
(ii) histidine buffer;
(iii) about 0.5 to 8 wt % Poloxamer 188; and
(iv) about 0.01 to 5 wt % methionine.
15. The composition of claim 4 , wherein the composition comprises:
(i) botulinum toxin serotype E (BoNT/E);
(ii) histidine buffer;
(iii) about 0.5 to 8 wt % Poloxamer 188;
(iv) about 0.01 to 5 wt % methionine; and
(v) NaCl.
16. The composition of claim 7 , wherein the composition comprises:
(i) botulinum toxin serotype E (BoNT/E);
(ii) histidine buffer;
(iii) about 0.5 to 8 wt % Poloxamer 188;
(iv) about 0.01 to 5 wt % methionine; and
(v) trehalose.
17. The composition of claim 1 , wherein the composition comprises:
(i) botulinum toxin serotype E (BoNT/E);
(ii) 20 mM histidine buffer;
(iii) about 4 wt % Poloxamer 188;
(iv) about 0.2 wt % methionine;
(v) about 8 wt % trehalose; and
(vi) about 0.2 wt % NaCl.
18. The composition of claim 1 , wherein the composition comprises:
(i) botulinum toxin serotype E (BoNT/E);
(ii) 20 mM histidine buffer;
(iii) about 4 wt % Poloxamer 188;
(iv) about 0.2 wt % methionine;
(v) about 2 wt % trehalose; and
(vi) about 0.2 wt % NaCl.
19. The composition of claim 1 , wherein the composition comprises:
(i) botulinum toxin serotype E (BoNT/E);
(ii) 20 mM histidine buffer;
(iii) about 4 wt % Poloxamer 188;
(iv) about 0.2 wt % methionine;
(v) about 8 wt % trehalose; and
(vi) about 0.6 wt % NaCl.
20. The composition of claim 1 , wherein the composition is lyophilized.
21. The composition of claim 1 , wherein the composition is vacuum dried.
22. The composition of claim 17 , wherein the composition is lyophilized.
23. The composition of claim 18 , wherein the composition is lyophilized.
24. The composition of claim 19 , wherein the composition is lyophilized.