Highly concentrated stabilized IgM solution
The present inventors discovered that stable and highly concentrated IgM solutions can be prepared by using, as an additive, a compound comprising a polyvalent cationic ion, such as magnesium chloride or arginine hydrochloride, to suppress IgM aggregation in solutions.
1. An aqueous solution of IgM comprising at least 1 mg/mL IgM, citrate buffer, and a polyvalent cation that is Mg++ or arginine ion, wherein the polyvalent cation is present at a concentration that suppresses by at least 10% the increase of water-soluble IgM aggregates produced during storage of the solution at a temperature selected from 4° C., 25° C., and 40° C., compared to the increase of water-soluble IgM aggregates seen with the same solution without the polyvalent cation.
2. The solution of claim 1 , wherein the polyvalent cation is Mg++.
3. The solution of claim 1 , wherein the polyvalent cation is arginine ion.
4. The solution of claim 1 , wherein the degree of suppression is at least 30%.
5. The solution of claim 1 , wherein the degree of suppression is at least 50%.
6. The solution of claim 1 , wherein the degree of suppression is at least 80%.
7. The solution of claim 1 , wherein the IgM concentration is 1-200 mg/mL.
8. The solution of claim 1 , wherein the concentration of IgM in the solution is higher than 10 mg/mL.
9. The solution of claim 1 , wherein the concentration of IgM in the solution is 20 mg/mL or more.
10. The solution of claim 1 , wherein the concentration of IgM in the solution is 25 mg/mL or more.
11. The solution of claim 1 , wherein the concentration of IgM in the solution is 40 mg/mL or more.
12. The solution of claim 1 , wherein the concentration of IgM in the solution is 50 mg/mL or more.
13. The solution of claim 1 , wherein the concentration of the polyvalent cation in the solution is 1 mM to 1000 mM.
14. The solution of claim 1 , wherein the concentration of the polyvalent cation in the solution is 10 mM to 500 mM.
15. The solution of claim 1 , wherein the concentration of the polyvalent cation in the solution is 50 mM to 200 mM.
16. The solution of claim 1 , wherein the pH of the solution is 5 to 8.
17. The solution of claim 1 , wherein the solution does not comprise proteins other than IgM.
18. A method for preparing the solution of claim 1 , the method comprising adding the polyvalent cation to a first solution comprising the IgM to form a second solution comprising the IgM at 1 mg/mL or more, citrate buffer, and the polyvalent cation.
19. The method of claim 18 , wherein the concentration of the IgM in the second solution is 20 mg/mL or more.
20. The method of claim 18 , further comprising storing the second solution at 4° C. to 25° C. for at least one month.
21. The method of claim 18 , further comprising freezing or lyophilizing the second solution.