US 7,837,881 B2 · Method and device for chromatographic purification

wherein the multi-component mixture (F) at least comprises light impurities (A), an intermediate product (B) to be purified and heavy impurities (C),

wherein columns are grouped into at least four sections (α,β,γ,δ), and wherein pairs of sequential functions of the sections (α;

β;

γ;

δ/δg,δf,δr) are combined within one column or a group of columns, the process comprising:

running alternatingly in a batch mode and an interconnected mode as follows:

A. in a batch mode,

(1) operating a first section (α), with at least one column in a batch mode position, wherein said first section (α) has at least one inlet for solvent (s) and at least one outlet for purified intermediate product (B), such that said first section (α) washes the purified intermediate product (B) out of the system, but keeps the heavy impurities (C) inside the first section (α);

(2) operating a first sub-section (δf) of the fourth section (δ), with at least one column in a batch mode position, wherein said first sub-section (δf) has at least one inlet for feeding in the multi-component mixture (F), and at least one outlet for direct removal of light impurities (A) out of the system;

(3) operating a third section (γ), with at least one column in a batch mode position, wherein said third section (γ) has at least one inlet for solvent (s) and an outlet for heavy impurities (C), such that said third section (γ) washes the heavy impurities (C) through said outlet out of the third section (γ) and cleans the chromatographic column(s) of the third section (γ),

wherein the functions of the sections (α,γ) and of the first sub-section (δf) are fulfilled synchronously;

and

B. in an interconnected mode

(1) operating a second section (β), with at least one column in an interconnected mode position, wherein said second section (β) has at least one inlet for solvent (s) and at least one outlet connected to an inlet of a second sub-section (δg) of a fourth section (δ), such that said second section (β) washes the intermediate product (B), which is contaminated with heavy impurities (C) into the second sub-section (δg) of the fourth section (δ) through said outlet, but keeps the pure heavy impurities (C) inside the second section (β);

(2) operating a third sub-section (δr) of the fourth section (δ), with at least one column, in an interconnected mode position wherein said third sub-section (δr) has at least one inlet for taking up output of the second sub-section (δg), and at least one outlet;

(3) operating a second sub-section (δg) of the fourth section (δ), with at least one column, in an interconnected mode position wherein said second sub-section (δg) has at least one inlet for taking up output of the second section (β) and at least one outlet connected to at least one input of the third sub-section (δr),

wherein the functions of the second section (β) and of the of the sub-sections (δg, δr) are fulfilled synchronously;

and

C. wherein after or within a switch time (t*) for switching from the batch mode to the interconnected mode the process further comprises:

moving the columns in their function in a counter direction to the general direction of flow of the solvent, in that:

the columns of the first section (α) are moved to become the second section (β),

the columns of the third section (γ) are moved to become the third sub-section (δr) of the fourth section (δ), and

the columns of the first sub-section (δf) are moved to become the second sub-section (δg) of the fourth section (δ);

and

D. wherein after or within a switch time (t*) for switching from the interconnected mode to the batch mode the columns are moved in their function in a counter direction to the general direction of flow of the solvent, in that:

the columns of the second section (β) are moved to become the third section (γ),

the columns of the third sub-section (δr) are moved to become the first sub-section (δf), and

the columns of the second sub-section (δg) are moved to become the first section (α), and

provided that, where a section comprises two columns, after or within a switch time (t*), the columns are moved in that:

(1) in case the section with two columns is one of second section (β), second sub-section (δg) or third sub-section (δr),

when switching from the batch mode to the interconnected mode:

the last column from the preceding section, is moved to the first position of the section with two columns,

a column of the section with two columns previously at a position where the flow rate is zero is moved to the second position of the section with two columns, and

when switching from the interconnected mode to the batch mode:

the first column of the section with two columns is moved to a position where the flow rate is zero, and

the last column of the section with two columns is moved to the next section;

and

(2) in case the section with two columns is one of first section (α), first sub-section (δf), or third section (γ),

when switching from the interconnected mode to the batch mode,

the last column from the preceding section, is moved to the first position of the section with two columns, and

a column of the section with two columns previously at a position where the flow rate is zero is moved to the second position of the section with two columns, and

when switching from the batch mode to the interconnected mode,

the first column of the section with two columns is moved to a position where the flow rate is zero, and

the last column of the section with two columns is moved to the next section.

Method and device for chromatographic purification

Life of this patent

Method and device for chromatographic purification

Life of this patent

Abstract

Claims18