Pharmaceutical compositions containing
This invention relates to compositions including Clostridium difficile toxins and/or toxoids and corresponding methods. The compositions of the invention include one or more excipients that increase stability and/or decrease aggregation of the toxins.
1. A composition comprising:
(a) a toxoid of Clostridium difficile toxin A and B;
(b) a sugar or sugar alcohol selected from sucrose, sorbitol, dextrose, and trehalose, at a concentration of 1-30%; and
(c) a surfactant at a concentration of up to 0.5%.
2. The composition of claim 1 , wherein the sugar or sugar alcohol is selected from sucrose, sorbitol, and trehalose at a concentration of 1-30%.
3. The composition of claim 1 , wherein the C. difficile toxoids A and B are present in the composition in a ratio of 5:1 (A:B) to 1:5 (A:B), or are present in the composition in a ratio of 3:1 to 3:2, or 1:1 (A:B).
4. The composition of claim 1 , wherein the sugar or sugar alcohol is at a concentration of 5-10%.
5. The composition of claim 1 , wherein the composition further comprises a buffer selected from a citrate, phosphate, glycine, histidine, carbonate, bicarbonate, and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer at a concentration of 5-100 mM.
6. The composition of claim 5 , wherein the buffer is a citrate buffer or a phosphate buffer at a concentration of 5-100 mM.
7. The composition of claim 5 , wherein the buffer is sodium citrate or potassium citrate.
8. The composition of claim 5 , wherein the buffer is sodium phosphate or potassium phosphate.
9. The composition of claim 5 , wherein the buffer is at a concentration of 10-30 mM.
10. The composition of claim 6 , wherein the buffer is at a concentration of 10-30 mM.
11. The composition of claim 1 , wherein the composition further comprises formaldehyde.
12. The composition of claim 1 , wherein the pH of the composition is 5.5-8.0.
13. The composition of claim 12 , wherein the pH of the composition is 6.5-8.0.
14. The composition of claim 1 , wherein the composition is a pharmaceutical composition.
15. The composition of claim 1 , wherein the composition further comprises an adjuvant.
16. The composition of claim 15 , wherein the adjuvant comprises an aluminum compound.
17. The composition of claim 16 , wherein the aluminum compound is an aluminum hydroxide compound.
18. The composition of claim 1 , wherein the composition is in liquid form.
19. A composition that is produced by drying the composition of claim 18 .
20. The composition of claim 5 , wherein the buffer and/or the sugar or sugar alcohol of the composition increases thermal stability of the toxoid and/or reduces aggregation of the toxoid, relative to a composition lacking the buffer and/or sugar or sugar alcohol.
21. The composition of claim 1 , wherein the surfactant is selected from the group consisting of polysorbate 80, polysorbate 20, and poloxamers.
22. The composition of claim 21 , wherein the surfactant is polysorbate 80 at a concentration of 0.05-0.1%.
23. The composition of claim 21 , wherein the surfactant is polysorbate 20 at a concentration of 0.01-0.05%.