Stable liquid formulations of botulinum toxin
The invention includes liquid formulations of botulinum toxin that are stable to storage in liquid form at standard refrigerator temperatures for at least 1-2 years and to storage at higher temperatures for at least 6 months. The invention also includes methods of treatment using such formulations for various therapeutic and cosmetic purposes.
1. A stable liquid pharmaceutical botulinum toxin formulation for therapeutic use in humans, comprising
a pharmaceutically acceptable buffer capable of providing a buffered pH range to the formulation of between about pH 5 and about pH 6;
sodium chloride;
a therapeutic concentration of a purified botulinum toxin suitable for use in humans, wherein said purified botulinum toxin has not been dried or lyophilized; and
serum albumin;
wherein the formulation is stable as a liquid when stored for at least one year at a temperature of about 5 degrees centigrade, or for at least 6 months at a temperature between about 10 and about 30 degrees centigrade.
2. The formulation of claim 1 , wherein said buffered pH is between about pH 5.4 and about pH 5.8.
3. The formulation of claim 1 , wherein said formulation is stable in liquid form for at least two years at a temperature of about 5 degrees centigrade.
4. The formulation of claim 1 , wherein said buffer is selected from the group consisting of phosphate buffer, phosphate-citrate buffer, and succinate buffer.
5. The formulation of claim 1 , wherein said botulinum toxin is a botulinum toxin serotype selected from the group consisting of serotypes A, B, C, D, E, F and G.
6. The formulation of claim 5 , wherein said botulinum toxin is botulinum toxin Type B present at said therapeutic concentration in the range of about 100 to about 20,000 U/ml.
7. The formulation of claim 6 , wherein said botulinum toxin Type B is present in a high molecular weight complex of about 700 kilodaltons (kD).
8. The formulation of claim 6 , wherein said botulinum toxin Type B is present at said therapeutic concentration between about 1000 to about 5000 U/ml.
9. The formulation of claim 5 , wherein said botulinum toxin is botulinum toxin Type A, present at said therapeutic concentration in the range of about 20-2000 U/ml.
10. The formulation of claim 9 , wherein said botulinum toxin Type A is present at said therapeutic concentration in the range of about 100-1000 U/ml.
11. A stable liquid pharmaceutical botulinum toxin formulation for therapeutic use in humans, comprising
about 0.5 mg/mL human serum albumin,
a pharmaceutically acceptable buffer capable of providing a buffered pH range between about pH 5 and about pH 6;
sodium chloride; and
botulinum toxin type B, wherein said botulinum type B is present at a concentration of about 5,000±1000 U/ml in said formulation;
wherein said botulinum toxin is stable in said formulation for at least about 6 months at a temperature between about 10 and about 30 degrees centigrade; and
wherein the stable liquid pharmaceutical botulinum toxin formulation is suitable for use without reconstitution of said botulinum toxin from a dried or lyophilized state prior to administration.
12. A stable liquid pharmaceutical botulinum toxin formulation for therapeutic use in humans, comprising
a pharmaceutically acceptable buffer capable of providing a buffered pH range to the formulation of between about pH 5 and pH 6;
sodium chloride;
a therapeutic concentration of a purified botulinum toxin suitable for use in humans, wherein said purified botulinum toxin has not been dried or lyophilized; and
serum albumin;
wherein said formulation is stable as a liquid when stored for at least one year at a temperature of between about 0 and 10 degrees centigrade, or for at least 6 months at a temperature of between about 10 and 30 degrees centigrade.
13. The formulation of claim 12 , wherein said buffer is selected from the group consisting of phosphate buffer, phosphate-citrate buffer, and succinate buffer.
14. The formulation of claim 12 , wherein said botulinum toxin comprises botulinum serotype B.