Method for sterilizing liquid chromatography resins highly resistant to oxidation and a sterilization solution for use therein

• US 5,676,837 A
• Filed: 06/07/1996
• Issued: 10/14/1997
• Est. Priority Date: 05/31/1994
• Status: Expired due to Term

• Current Assignee: Pall Corporation (Danaher Corporation)
• Original Assignee: BioSepra, Inc. (Danaher Corporation)
• Inventors: Lettner, Hans Peter, Jungbauer, Alois
• Primary Examiner(s): Therkorn, Ernest G.
• Application Number:
  US08/662,262
• Time in Patent Office: 494 Days
• Field of Search: 210/635, 210/656, 210/759, 210/764, 210/198.2, 210/501, 210/502.1, 422/28, 422/30
• US Class Current: 210/635
• CPC Class Codes: A01N 2300/00 Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
• CPC Class Codes: A01N 25/02 containing liquids as carriers, diluents or solvents
• CPC Class Codes: A01N 31/02 Acyclic compounds
• CPC Class Codes: A01N 37/16 containing the group; Thio analogues thereof
• CPC Class Codes: A61L 2/18 Liquid substances or solutions comprising solids or dissolved gases
• CPC Class Codes: B01D 15/08 Selective adsorption, e.g. chromatography
• CPC Class Codes: B01J 20/281 Sorbents specially adapted for preparative, analytical or investigative chromatography
• CPC Class Codes: B01J 2220/54 Sorbents specially adapted for analytical or investigative chromatography
• CPC Class Codes: G01N 30/50 Conditioning of the sorbent material or stationary liquid

Abstract

A method for sterilizing liquid chromatography resins that are highly resistant to oxidation by strongly oxidizing agents and a sterilization solution for use therein. In a preferred embodiment, the invention comprises contacting an oxidant-resistant chromatographic resin with an aqueous solution of peracetic acid and up to 40% ethanol. In particular, where the solution is to be used to sterilize a positively charged ion-exchange resin, the solution preferably additionally includes an acetate buffer of a sufficient ionic strength to prevent adsorption of the peracetic acid ions on the resin.

Claims

1. A method for sterilizing a chromatography resin that is highly resistant to oxidation by strongly oxidizing agents without generation of toxic end products, said method comprising the step of washing the chromatography resin with an aqueous solution of a percarboxylic acid, said aqueous solution including an acetate buffer in a concentration of about 0.1 to 2M.

2. The method as claimed in claim 1 wherein said percarboxylic acid is peracetic acid.

3. The method as claimed in claim 2 wherein said acetate buffer has a concentration of about 0.5M.

4. The method as claimed in claim 3 wherein said aqueous solution has a pH of about 5.

5. The method as claimed in claim 4 wherein said peracetic acid has a concentration of about 500 mg/l to about 5000 mg/l.

6. The method as claimed in claim 5 wherein said peracetic acid has a concentration of about 1500 mg/l to about 5000 mg/l.

7. The method as claimed in claim 2 wherein said peracetic acid has a concentration of about 500 mg/l to about 5000 mg/l.

8. The method as claimed in claim 7 wherein said peracetic acid has a concentration of about 1500 mg/l to about 5000 mg/l.

9. The method as claimed in claim 2 wherein said washing step is performed at about 4°

C. to about 25°

C.

10. The method as claimed in claim 1 wherein said aqueous solution has a pH of about 5.

11. The method as claimed in claim 1 wherein the chromatography resin comprises a passivated porous support comprising (i) a porous mineral oxide matrix having interior and exterior surfaces substantially covered by a thin, protective polymer surface coating having innate hydrophobic groups that render said coating susceptible to undesirable non-specific interaction with one or more biological molecules, and (ii) a polymer network derived from a passivation mixture comprising a main monomer, a passivated monomer different from said main monomer, and a crosslinking agent, said mixture having been allowed to come into intimate contact with said surfaces of said coating such that on polymerization of said mixture said innate groups of said coating become deactivated, resulting in the substantial elimination of said undesirable non-specific interaction.

12. A method for sterilizing a chromatography resin that is highly resistant to oxidation by strongly oxidizing agents without generation of toxic end products, said method comprising the step of washing the chromatography resin with an aqueous solution of a percarboxylic acid, said aqueous solution including an acetate buffer in a concentration of about 0.1 to 2M and an alcohol.

13. The method as claimed in claim 12 wherein said percarboxylic acid is peracetic acid.

14. The method as claimed in claim 13 wherein said alcohol is ethanol.

15. The method as claimed in claim 14 wherein the concentration of ethanol in said aqueous solution is no greater than about 40%.

16. The method as claimed in claim 15 wherein the concentration of ethanol in said aqueous solution is about 20%.

17. The method as claimed in claim 13 wherein said acetate buffer has a concentration of about 0.5M.

18. The method as claimed in claim 17 wherein said aqueous solution has a pH of about 5.

19. The method as claimed in claim 18 wherein said peracetic acid has a concentration of about 500 mg/l to about 5000 mg/l.

20. The method as claimed in claim 19 wherein said peracetic acid has a concentration of about 1500 mg/l to about 5000 mg/l.

21. The method as claimed in claim 20 wherein the alcohol in said aqueous solution is ethanol in a concentration of about 20%.

22. The method as claimed in claim 21 wherein said washing step is performed at about 4°

C. to about at 25°

C.

23. The method as claimed in claim 13 wherein said peracetic acid has a concentration of about 500 mg/l to about 5000 mg/l.

24. The method as claimed in claim 23 wherein said peracetic acid has a concentration of about 1500 mg/l to about 5000 mg/l.

25. The method as claimed in claim 13 wherein said washing step is performed at about 4°

C. to about 25°

C.

26. The method as claimed in claim 12 wherein said aqueous solution has a pH of about 5.

27. The method as claimed in claim 12 wherein the chromatography resin comprises a passivated porous support comprising (i) a porous mineral oxide matrix having interior and exterior surfaces substantially covered by a thin, protective polymer surface coating having innate hydrophobic groups that render said coating susceptible to undesirable non-specific interaction with one or more biological molecules, and (ii) a polymer network derived from a passivation mixture comprising a main monomer, a passivated monomer different from said main monomer, and a crosslinking agent, said mixture having been allowed to come into intimate contact with said surfaces of said coating such that on polymerization of said mixture said innate groups of said coating become deactivated, resulting in the substantial elimination of said non-specific interaction.