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 liquid pharmaceutical composition which is free of protein excipients, the composition comprising:
(i) a Clostridial botulinum toxin active ingredient;
(ii) an aqueous carrier;
(iii) a poloxamer surfactant; and
(iv) methionine in an amount between about 0.01 to 5 wt %;
wherein the composition is suitable for subcutaneous or intramuscular injection; and wherein the composition is stable for at least one month at 40° C.
2. The liquid pharmaceutical composition of claim 1 , wherein the composition further comprises trehalose.
3. The liquid pharmaceutical composition of claim 2 , wherein trehalose is present in an amount between about 1 to 15 wt %.
4. The liquid pharmaceutical composition of claim 1 , wherein the poloxamer is poloxamer P188.
5. The liquid pharmaceutical composition of claim 1 , wherein the poloxamer is present in an amount between about 0.5 to 8 wt %.
6. The liquid pharmaceutical composition of claim 1 , wherein methionine is present in an amount between about 0.01 to 0.5 wt %.
7. The liquid pharmaceutical composition of claim 1 , wherein the composition comprises trehalose and poloxamer P188.
8. A liquid pharmaceutical composition which is free of protein excipients, the composition comprising:
(i) a Clostridial botulinum toxin active ingredient;
(ii) trehalose in an amount between about 1-15 wt %;
(iii) a poloxamer in an amount between about 0.5-8 wt %; and
(iv) methionine in an amount between about 0.05-5 wt %,
wherein the composition is suitable for subcutaneous or intramuscular injection; and wherein the composition is stable for at least one month at 40° C.
9. The liquid pharmaceutical composition of claim 8 , wherein methionine is present in an amount between about 0.05-2 wt %.
10. The liquid pharmaceutical composition of claim 8 , wherein the poloxamer is present in an amount between about 2-6 wt %.
11. The liquid pharmaceutical composition of claim 8 , wherein trehalose is present in an amount between about 5-12 wt %.
12. A method for treating depression, comprising: providing for administration a composition of claim 1 .
13. A method for treating cardiac arrhythmia, comprising: providing for administration a composition of claim 1 .
14. A method for treating depression, comprising: providing for administration a composition of claim 8 .
15. A method for treating cardiac arrhythmia, comprising: providing for administration a composition of claim 8 .
16. A liquid pharmaceutical composition which is free of protein excipients, the composition comprising:
a Clostridial botulinum toxin active ingredient,
poloxamer P188 in an amount between about 0.6-4 wt %,
trehalose in an amount between about 2-8 wt %,
methionine in an amount between about 0.05-5 wt %, and
a 20 mM histidine buffer.
17. The liquid pharmaceutical composition of claim 16 , wherein the composition comprises
trehalose in an amount of about 8 wt %,
poloxamer P 188 in an amount of about 4 wt %,
methionine in an amount of about 0.2 wt %, and
a 20 mM histidine buffer at a pH of about 6.0.
18. The liquid pharmaceutical composition of claim 16 , wherein the composition comprises
trehalose in an amount of about 2 wt %,
poloxamer P188 in an amount of about 4 wt %,
sodium chloride in an amount of about 0.6 wt %,
methionine in an amount of about 0.2 wt %, and
a 20 mM histidine buffer at a pH of about 6.0.
19. The liquid pharmaceutical composition of claim 16 , wherein the composition comprises
trehalose in an amount of about 8 wt %,
poloxamer P 188 in an amount of about 4 wt %,
methionine in an amount of about 0.2 wt %,
EDTA in an amount of about 0.03 wt %, and
a 20 mM histidine buffer at a pH of about 6.0.