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/or B;
(b) a buffer selected from a citrate, phosphate, glycine, histidine, carbonate, bicarbonate, and HEPES buffer at a concentration of 5-100 mM; and
(c) a sugar or sugar alcohol selected from sucrose, sorbitol, dextrose, and trehalose at a concentration of 1-30%;
wherein the pH of the composition is 5.5-8.0.
2. The composition of claim 1 , wherein the buffer is a citrate buffer or a phosphate buffer at a concentration of 5-100 mM; and the sugar or sugar alcohol is selected from sucrose, sorbitol, and trehalose at a concentration of 1-30%.
3. The composition of claim 2 , wherein the composition comprises a toxoid of Clostridium difficile toxins A and B.
4. The composition of claim 3 , 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).
5. The composition of claim 2 , wherein the buffer is sodium citrate or potassium citrate.
6. The composition of claim 2 , wherein the buffer is sodium phosphate or potassium phosphate.
7. The composition of claim 5 , wherein the buffer is at a concentration of 10-30 mM.
8. The composition of claim 6 , wherein the buffer is at a concentration of 10-30 mM.
9. The composition of claim 2 , wherein the sugar or sugar alcohol is at a concentration of 5-10%.
10. The composition of claim 2 , further comprising formaldehyde.
11. The composition of claim 2 , wherein the pH of the composition is 6.5-8.0.
12. The composition of claim 2 , wherein the composition is a pharmaceutical composition.
13. The composition of claim 2 , further comprising an adjuvant.
14. The composition of claim 13 , wherein the adjuvant comprises an aluminum compound.
15. The composition of claim 14 , wherein the aluminum compound is an aluminum hydroxide compound.
16. The composition of claim 2 , wherein the composition is in liquid form.
17. A composition that is produced by drying the composition of claim 16 .
18. The composition of claim 2 , wherein the buffer and/or the sugar or sugar alcohol increase thermal stability of the toxoid and/or reduce aggregation of the toxoid, relative to a composition lacking the buffer and/or sugar or sugar alcohol.
19. A composition comprising
(a) a toxoid of Clostridium difficile toxin A and/or B;
(b) sodium or potassium citrate (5-100 mM);
(c) sucrose (2-20%); and
(d) formaldehyde;
wherein the pH of the composition is 5.5-8.5.
20. The composition of claim 19 , comprising sodium or potassium citrate in the amount of 10-30 mM, sucrose in the amount of 2-10%, and formaldehyde in the amount of 0.01-0.018%, wherein the pH of the composition is 6.5-8.0.
21. The composition of claim 19 , comprising a toxoid of Clostridium difficile toxin A and toxin B.
22. The composition of claim 19 , wherein the composition is in liquid form.
23. A composition that is produced by drying the composition of claim 22 .
24. A composition comprising
(a) a toxoid of Clostridium difficile toxin A and/or B;
(b) sodium or potassium phosphate (5-100 mM);
(c) sucrose (2-20%); and
(d) formaldehyde;
wherein the pH of the composition is 5.5-8.5.
25. The composition of claim 24 , comprising sodium or potassium phosphate in the amount of 10-30 mM, sucrose in the amount of 2-10%, and formaldehyde in the amount of 0.01-0.018%, wherein the pH of the composition is 6.5-8.0.
26. The composition of claim 24 , comprising a toxoid of Clostridium difficile toxin A and toxin B.
27. The composition of claim 24 , wherein the composition is in liquid form.
28. A composition that is produced by drying the composition of claim 27 .
29. A method of making the composition of claim 1 , the method comprising providing a toxoid of Clostridium difficile toxin A and/or B, and admixing the toxoid with (a) a buffer selected from a citrate, phosphate, glycine, histidine, carbonate, bicarbonate, and HEPES buffer at a concentration of 5-100 mM, and (b) a sugar or sugar alcohol selected from sucrose, sorbitol, dextrose, and trehalose at a concentration of 1-30%.