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 liquid pharmaceutical composition, the composition comprising:
(i) a Clostridial botulinum serotype A toxin active ingredient in an amount of about 1.0 U/ml to about 1,000 U/ml;
(ii) a tonicity agent selected from trehalose, sucrose, sodium chloride, mannitol, sorbitol, glucose, and combinations thereof;
(iii) a poloxamer surfactant;
(iv) methionine in an amount between about 0.01 to 5 wt %; and
(v) a buffering agent,
wherein the composition has a pH of between about 5 and 8; wherein the composition is suitable for subcutaneous or intramuscular injection; and wherein the composition is stable for at least one month at 5° C.
2 . (canceled)
3 . The stable liquid pharmaceutical composition of claim 1 , wherein the composition further comprises trehalose.
4 . The stable liquid pharmaceutical composition of claim 3 , wherein trehalose is present in an amount between about 1 to 15 wt %.
5 . The stable liquid pharmaceutical composition of claim 1 , wherein the poloxamer surfactant is poloxamer 188 (P188).
6 . The stable liquid pharmaceutical composition of claim 5 , wherein the poloxamer surfactant is present in an amount between about 0.5 to 8 wt %.
7 . (canceled)
8 . (canceled)
9 . The stable liquid pharmaceutical composition of claim 1 , wherein the composition comprises trehalose and poloxamer 188 (P188).
10 . (canceled)
11 . A stable liquid pharmaceutical composition, the composition comprising:
(i) a Clostridial botulinum serotype A toxin active ingredient in an amount of about 1.0 U/ml to about 1,000 U/ml;
(ii) an aqueous carrier;
(iii) at least one tonicity agent;
(iv) poloxamer 188 (P188) in an amount between about 0.5-8 wt %;
(v) methionine in an amount between about 0.05-5 wt %; and
(vi) a buffer,
wherein the composition is isotonic and has a pH of between about 5-8, wherein the composition is suitable for subcutaneous or intramuscular injection, and wherein the composition is stable for at least one month at 5° C.
12 . (canceled)
13 . The stable liquid pharmaceutical composition of claim 11 , wherein methionine is present in an amount between about 0.05-2 wt %.
14 . The stable liquid pharmaceutical composition of claim 11 , wherein the P188 is present in an amount between about 2-6 wt %.
15 . The stable liquid pharmaceutical composition of claim 11 , wherein the at least one tonicity agent comprises NaCl and/or trehalose in an amount between about 1-15 wt %.
16 - 19 . (canceled)
20 . A stable liquid pharmaceutical composition, the composition comprising:
(i) a Clostridial botulinum serotype A toxin active ingredient in an amount of between about 1.0 U/ml to about 1,000 U/ml;
(ii) an aqueous carrier;
(iii) at least one tonicity agent;
(iii) P188 in an amount between about 0.6-4 wt %;
(iv) trehalose in an amount between about 2-8 wt %;
(v) methionine in an amount between about 0.05-5 wt %; and
(vi) histidine buffer,
wherein the composition has a pH of between about 5-8; wherein the composition is suitable for subcutaneous or intramuscular injection; and wherein the composition is stable for at least one month at 5° C.
21 . The stable liquid pharmaceutical composition of claim 20 , wherein the composition comprises:
a Clostridial botulinum serotype A toxin active ingredient in an amount of about 40 U/ml,
trehalose in an amount of about 8 wt %,
P188 in an amount of about 4 wt %,
methionine in an amount of about 0.2 wt %, and
about 20 mM histidine buffer,
wherein the composition has a pH of about 6.0.
22 . The stable liquid pharmaceutical composition of claim 20 , wherein the composition comprises:
a Clostridial botulinum serotype A toxin active ingredient in an amount of about 40 U/ml,
trehalose in an amount of about 2 wt %,
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
about 20 mM histidine buffer,
wherein the composition has a pH of about 6.0.
23 . The stable liquid pharmaceutical composition of claim 20 , wherein the composition comprises
a Clostridial botulinum serotype A toxin active ingredient in an amount of about 40 U/ml,
trehalose in an amount of about 8 wt %,
poloxamer P188 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.
24 . The stable liquid pharmaceutical composition of claim 1 , wherein the composition retains at least 50% potency after one month of storage at 5° C.
25 . The stable liquid pharmaceutical composition of claim 11 , wherein the composition retains at least 50% potency after one month of storage at 5° C.
26 . The stable liquid pharmaceutical composition of claim 20 , wherein the composition retains at least 50% potency after one month of storage at 5° C.