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) botulinum toxin serotype A (BoNT/A);
(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 composition comprises about 1 unit to about 1000 mouse LD 50 units of BoNT/A.
3. The composition of claim 1 , wherein the composition comprises about 1 ng to about 1 ug of BoNT/A.
4. The compositin of claim 1 , wherein the botulinum toxin serotype A (BoNT/A) comprises the approximately 150 kDa neurotoxin unassociated with complex proteins.
5. The composition of claim 1 , wherein the poloxamer surfactant comprises poloxamer 188.
6. The composition of claim 1 , wherein the composition further comprises a disaccharide.
7. The composition of claim 6 , wherein the disaccharide is selected from sucrose or trehalose.
8. The composition of claim 6 , wherein the disaccharide comprises trehalose.
9. The composition of claim 1 , wherein the aqueous carrier coprises a buffer.
10. The composition of claim 9 , wherein the buffer comprises histidine buffer.
11. The composition of claim 1 , wherein the composition comprises:
(i) botulinum toxin serotype A (BoNT/A);
(ii) about 0.5 to 8 wt % of a poloxamer surfactant; and
(iii) about 0.01 to 5 wt % methionine.
12. The composition of claim 1 , wherein the composition comprises:
(i) botulinum toxin serotype A (BoNT/A);
(ii) histidine buffer;
(iii) about 0.5 to 8 wt % of a poloxamer surfactant; and
(iv) about 0.01 to 5 wt % methionine.
13. The composition of claim 1 , wherein the composition comprises:
(i) botulinum toxin serotype A (BoNT/A);
(ii) histidine buffer;
(iii) about 0.5 to 8 wt % Poloxamer 188; and
(iv) about 0.01 to 5 wt % methionine.
14. The composition of claim 1 , wherein the composition comprises:
(i) botulinum toxin serotype A (BoNT/A);
(ii) histidine buffer;
(iii) about 0.5 to 8 wt % Poloxamer 188;
(iv) about 0.01 to 5 wt % methionine; and
(v) trehalose.
15. The composition of claim 1 , wherein the composition comprises:
(i) botulinum toxin serotype A (BoNT/A);
(ii) 20 mM histidine buffer;
(iii) about 4 wt % Poloxamer 188;
(iv) about 0.2 wt % methionine;
(v) about 8 wt % trehalose.
16. The composition of claim 15 , wherein the composition comprises:
(i) botulinum toxin serotype A (BoNT/A);
(ii) 20 mM histidine buffer;
(iii) about 4 wt % methionine;
(iv) about 0.2 wt % methionine;
(v) about 8 wt % trehalose, and
wherein the composition comprises about 1 ng to about 1 ug of BoNT/A, and
wherein the composition is lyophilized.
17. The composition of claim 1 , wherein the composition is lyophilized.
18. The composition of claim 1 , wherein the compositoin is vacuum dried.