Method for the manufacture of compositions containing low concentrations of salts
View Patent ↗Method for desalting an aqueous liquid containing a charged substance comprising the steps of: (i) contacting liquid (I) with an ion-exchanger (1) under conditions permitting binding between ion-exchanger and substance, said ion-exchanger comprising a base matrix carrying an ion-exchange ligand (Ligand 1) with the opposite charge compared to the substance, (ii) desorbing said substance from said ion-exchanger by the use of a liquid (liquid (II)). Wherein: (A) ion-exchanger (1) is an ion-exchanger: (a) that can bind the substance in an aqueous reference liquid at ionic strength corresponding to 0.1 M NaCl, preferably 0.25 M NaCl; and (b) permits a breakthrough capacity at the pH provided by liquid (I) which is more than 2 mg/ml of gel, at a breakthrough of 10% and linear flow velocity of 300 cm/h; and (B) in step (ii) the pH of liquid (11) is adjusted to a pH value where the charge difference between the substance, the ligand and/or the ion-exchanger is lowered.
1. A method for desalting an aqueous liquid containing a charged substance comprising the steps of:
(i) contacting liquid (I) with an ion-exchanger (1) under conditions permitting binding between the ion-exchanger and the substance, said ion exchanger comprising a base matrix carrying an ion-exchange ligand (Ligand 1) that has the opposite charge compared to the substance,
(ii) desorbing said substance from said ion-exchanger by the use of a liquid (liquid (II)),
wherein
(A) ion-exchanger (1) is selected among ion-exchangers that:
(a) are capable of binding the substance of interest in an aqueous reference liquid at an ionic strength corresponding to 0.1 M NaCl; and
(b) permit a breakthrough capacity at the pH provided by liquid (I) which is more than 2 mg/ml of gel (sedimented), at a breakthrough of 10% and a linear flow velocity of 300 cm/h;
and
(B) step (ii) comprises that the pH of liquid (II) is adjusted to a pH value that means that the charge difference between the substance and the ligand and/or the ion-exchanger is lowered.
2. The method of claim 1 , wherein the substance is bio-organic and amphoteric with two or more charged groups and a molecular weight above 1,000 Dalton.
3. The method of claim 1 , wherein the adjustment leads to zero charge on the substance and/or on Ligand 1/ion-exchanger or to a charge of the same kind for both of them (either negative or positive).
4. The method of claim 1 , wherein Ligand 1 is a cation-exchange ligand a mixed mode cation-exchange ligand.
5. The method of claim 1 , wherein Ligand 1 is an anion-exchange ligand a mixed mode anion-exchange ligand.
6. The method of claim 1 , wherein Ligand 1 have a pH-independent charge or can be decharged by a pH-switch.
7. The method of claim 1 , wherein the ion-exchanger is stochastic and comprises also a second ligand (Ligand 2).
8. The method of claim 7 , wherein Ligand 2 at the condition provided by liquid (I) is (a) uncharged but chargeable by a pH switch, or (b) uncharged and not chargeable, or (c) charged by a pH-independent charge, or (d) charged by a pH-dependent charge.
9. The method of claim 7 , wherein Ligand 2 is a mixed mode ligand.
10. The method of claim 1 , wherein
(a) in liquid (I) the ionic strength is at least the ionic strength corresponding to 0.1 M NaCl, and
(b) in liquid (II) the ionic strength contribution from non-buffering components and their associated counter-ions is at most 10% of the ionic strength of liquid (I), with preference for said ionic strength contribution in liquid (II) being at most the ionic strength of a 0.01 M NaCl.
11. The method of claim 1 , wherein the buffer used in step (ii) is volatile and is evaporated in a step preceding step (ii).
12. The method of claim 1 , wherein the substance to be desalted is present in liquid (II) after step (ii) in a concentration that is at least 10 times the concentration in liquid (I).
13. The method of claim 1 , wherein
(a) the substance is present in liquid (I) together with other substances comprising a structure selected amongst peptide structure nucleic acid structure, carbohydrate structure, lipid structure, steroid structure, amino acid structure, nucleotide structure, and
(b) the total amount of these other substances are reduced with at least a factor 10 after step (ii) in a fraction of liquid (II) that also contains the substance to be desalted.
14. The method of claim 1 , wherein liquid (I) consists essentially of the substance to be desalted, salts and an aqueous solvent.
15. The method of claim 1 , wherein liquid II containing the substance after step (ii) is further processed to a dry form, either directly or indirectly.
16. The method of claim 1 , wherein the method is a part of an analytical procedure or of a process for manufacturing a composition containing the desalted substance or a derivative thereof,
said composition being intended to be used as a pharmaceutical or within the food industry.
17. The method of claim 1 , wherein the ion exchanger has been selected amongst those ion exchangers that permit a maximal breakthrough capacity in the pH interval 2-12 for the substance which is ≧100% of the breakthrough capacity of the substance for the corresponding ion-exchanger in which the ion-exchange ligands are
(i) sulphopropyl groups when the substance has a positive charge (reference ion-exchanger 2a), and
(ii) quaternary ammonium groups when the substance has a negative charge (reference ion-exchanger 2b); the measurements being performed under essentially the same conditions for ion-exchanger (I) and (2a) and for ion-exchanger (I) and (2b).