Regeneration of chromatographic stationary phases

• US 9,364,772 B2
• Filed: 04/07/2008
• Issued: 06/14/2016
• Est. Priority Date: 04/08/2003
• Status: Active Grant

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Rasmussen, Eigil Schroder, Larsen, Per, Schou, Ole
• Primary Examiner(s): Zalasky, Katherine
• Application Number:
  US12/098,779
• Publication Number:
  US 20080312131A1
• Time in Patent Office: 2,990 Days
• Field of Search: 210/635, 210/638, 210/656, 210/659, 210/674
• US Class Current: 1/1
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: B01D 15/20 relating to the conditioning of the sorbent material
• CPC Class Codes: B01D 15/203 Equilibration or regeneration
• CPC Class Codes: B01J 20/283 based on silica
• CPC Class Codes: B01J 20/285 based on polymers
• CPC Class Codes: B01J 20/34 Regenerating or reactivating
• CPC Class Codes: B01J 20/3425 of sorbents or filter aids comprising organic materials
• CPC Class Codes: B01J 20/3433 of sorbents or filter aids other than those covered by B01J20/3408 - B01J20/3425
• CPC Class Codes: B01J 20/3475 in the liquid phase
• CPC Class Codes: C07K 1/20 Partition-, reverse-phase or hydrophobic interaction chromatography

Abstract

Process for regenerating a chromatographic stationary phase.

Claims

1. A process for regenerating a silica material or a substituted silica material chromatographic stationary phase comprising contacting said silica material or a substituted silica material chromatographic stationary phase at a temperature in the range from about 0°

C. to about 70°

C. with a regeneration solution comprising at least one organic acid and less than about 75% w/w water, wherein said organic acid is formic acid, wherein the concentration of formic acid is at least 25% w/w, and wherein said chromatographic stationary phase is a Reverse Phase-High Pressure Liquid Chromatography (RP-HPLC) matrix.

2. The process according to claim 1, wherein the regeneration solution comprises at least one organic acid and less than about 1% w/w water.

3. The process according to claim 1, wherein said regeneration solution contains less than 0.5% water.

4. The process according to claim 1, wherein said chromatographic stationary phase is contacted with said regeneration solution inside the chromatographic column.

5. The process according to claim 4, wherein said chromatographic stationary phase is regenerated without repacking the column.

6. The process according to claim 4, wherein said chromatographic stationary phase is fluidized during said regeneration.

7. The process according to claim 4, wherein a chromatographic eluent or equilibrium buffer is displaced by a water miscible organic solvent before said chromatographic stationary phase is contacted with said regeneration solution.

8. The process according to claim 7, wherein said organic solvent is also present in the chromatographic eluent or equilibrium buffer.

9. The process according to claim 8, wherein said water miscible organic solvent is also present in the regeneration solution.

10. The process according to claim 1, wherein said chromatographic stationary phase is contacted with said regeneration solution outside the chromatographic column.

11. The process according to claim 1, wherein said chromatographic stationary phase is C16 or C18 substituted silica.

12. The process according to claim 1, wherein said chromatographic stationary phase is C4, C8 or phenyl-substituted silica.

13. The process according to claim 1, wherein said chromatographic stationary phase is contacted with said regeneration solution for at least 1 minute.

14. The process according to claim 1, wherein said chromatographic stationary phase is contacted with said regeneration solution until the pressure drop over the length of the chromatographic column at normal flow rate decreases by at least 10%.

15. The process according to claim 1, wherein contacting of said chromatographic stationary phase with said regeneration solution is performed at a temperature in the range from about 5°

C. to 50°

C.

16. The process according to claim 1, wherein the life time of said chromatographic stationary phase is at least 500 chromatographic cycles.

17. The process according to claim 1, wherein said process is applied to said chromatographic stationary phase for every chromatographic cycle.

18. The process according to claim 1, wherein said process is applied to said chromatographic stationary phase at least once every 100 chromatographic cycles.