CN107185273A - The method and its equipment of a kind of continuous chromatography - Google Patents
The method and its equipment of a kind of continuous chromatography Download PDFInfo
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- CN107185273A CN107185273A CN201710450149.3A CN201710450149A CN107185273A CN 107185273 A CN107185273 A CN 107185273A CN 201710450149 A CN201710450149 A CN 201710450149A CN 107185273 A CN107185273 A CN 107185273A
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/265—Adsorption chromatography
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/12—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the preparation of the feed
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/18—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns
- B01D15/1814—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns recycling of the fraction to be distributed
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/18—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns
- B01D15/1864—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns using two or more columns
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/18—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns
- B01D15/1892—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns the sorbent material moving as a whole, e.g. continuous annular chromatography, true moving beds
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- Life Sciences & Earth Sciences (AREA)
- Sustainable Development (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
Abstract
The invention provides a kind of method of continuous chromatography and its equipment, it is characterised in that：Described to be equipped for multicolumn continuous chromatography system, the system is divided into Liang great Qu：Crude separation area and smart Disengagement zone；Crude separation area is made up of five subprovinces：Loading area, Qu Qianza areas, the areas of Qu Houza 1, sample elution area, the areas of Qu Houza 2, are defined as I, II, III, IV and V area successively；Smart Disengagement zone is made up of two subprovinces：Smart Disengagement zone and sample elution area, are defined as VI and VII area successively；The subprovince is constituted by 1 to branched Coupled columns, is connected between chromatographic column and chromatographic column by pipeline or/and valve interface；Chromatographic process is on this system：Many component samples are in I area's Pulsed Sampling；After single injected sampling, through valve transfer, Ith area end post carry is the first post in IIth area, miscellaneous before being removed in IIth area（Target compound is eluted to and just breaks through IIth area）；Through valve transfer, IIth area end post carry is the first post in IVth area, and target compound is eluted to just completely into the last post in IVth area in IVth area；It is miscellaneous after being removed in III and V area；Through valve transfer, IVth area end post carry is the first post in VIth area, and sample is finely separated in VIth area（Target compound is eluted to and just penetrates VIth area）；Through valve transfer, the last post carry in VIth area is the first post in VIIth area, Fractional Collections target compound is eluted in VIIth area and containing a small amount of rear miscellaneous target compound；Methods described is realized by intelligent controls such as valve transfer, the start and stop of pump or/and flow velocity regulation and control.
Description
Technical field
The present invention relates to a kind of method of continuous chromatography and its equipment, the method for more particularly to a kind of multicolumn continuous chromatography and
It is equipped.
Background technology
Chromatographic separation and purification technology is to obtain the indispensable important means of high-purity compound.In all separating and purifying technologies
In, chromatogram is minimum production capacity, cost highest, operator quality requirement height, operates fine, time-consuming, effort technology.For many years
Come, people are directed to lifting the production capacity of chromatographic technique always, reduce its cost, and make its simple to operate.
Separation object typically contains preceding miscellaneous, target compound and rear miscellaneous.According to the difficulty or ease of separation, chromatogram is divided into displcement chromatography
（Displacement Chromatography）And elution chromatography（Elution Chromatography）.Displcement chromatography is suitable to
The separation of retention and the widely different impurity of target compound retention, is generally used for the enrichment or preliminary pure of target compound
Change.Elution chromatography is suitable to target compound and separated with the fine of other impurities.According to the continuity of chromatographic process, chromatogram is divided into again
Continuous chromatography（Continuous Chromatography）And single column chromatographic（Batch Chromatography）.Continuous elution
Chromatogram is subdivided into Simulation moving bed（Simulated Moving Bed, SMB）With continuous single column chromatographic（Continuous
Batch Chromatography, CBC）.Comparatively, continuous chromatography has higher separating capacity, higher production capacity and more
Low consumption.
SMB technologies are initiated by doctor Broughton, oil product company of the U.S. in 1961（UOP）SMB is disclosed in petrochemical industry
Upper application（United States Patent (USP) 2985589）.Hereafter, SMB technologies are obtained constantly improving and improved【United States Patent (USP) 3706812,
4157267、4267054、4293346、4312678、4313015、4332623、4359430、4379751、4402832、
4412866、4461649、4533398、5064539、5127957、5387347、6331250、6896811、7229558、
7479228th, 8282831,8496836 etc., its attention has Varicol technologies（WO-A-2004/039468）、
Powerfeed technologies（Journal of Chromatography A, 2003, 1006:87-99）, Modicon technologies (WO
2004/014511) with Solvent Gradient pattern（United States Patent (USP) 4031155）Deng】So that SMB turns into most widely used chromatogram mould
Formula.
Although once SMB is used for the report that many mixtures are separated（United States Patent (USP) 6331250,7479228 and
8282831 etc.）, however, it is difficult to high production capacity obtain high-purity target compound, this kind of technology typically utilizes SMB powerful production
Crude separation can be carried out to many mixtures, to reduce the load of follow-up chromatogram, strengthen the production capacity of follow-up chromatogram.In principle, SMB
Only it is suitable to the separation of 2 mixtures, when SMB is used for the separation of three mixtures, otherwise separate two on same device
It is secondary, otherwise linked with 2 sets of SMB devices.SMB production capacity is generally 2~10 times of single column chromatographic, and the production capacity of continuous single column chromatographic is
2~4 times of single column chromatographic.Thus, for the separation of many mixtures, SMB not necessarily has more advantage than continuous single column chromatographic.
For the separation of some 2 mixtures, continuous single column chromatographic has more advantage than SMB.This has evoked people to continuous single-column color
The research of spectrum.
Single column chromatographic is met at one carries out loading, preceding miscellaneous, the elution mesh of elution successively in the chromatographic column of length needed for separation
Miscellaneous wait after compound and elution is marked to operate.The filler utilization rate of single column chromatographic is low, solvent load is big, time-consuming, production capacity is low.Can be with
Under software control, above-mentioned single column chromatographic process is made automatically continuously to carry out.But, the production capacity of this continuous process depends on sample introduction
Frequency, and sample introduction frequency is determined by total peak width of many mixtures（The rear of previous sample miscellaneous can not cover latter sample
Target peak, the preceding of latter sample miscellaneous can not cover the target peak of previous sample）.Thus, this continuous single column chromatographic is to single-column color
The defect of spectrum does not have essential improvement.
Snyder etc.（United States Patent (USP) 4204952,1980）By length needed for short two chromatographic column composition separation of a length
Chromatographic column, substantial amounts of pre-impurity and post-impurity are removed on short column, the target mixture by rough segmentation is finely divided by long column again
From；Thus total peak width is significantly reduced, sample introduction frequency is improved, enhances chromatogram separating capacity, production capacity is improved one
More than times.The technical equipment is simple, can use the filler of two kinds of different stalling characteristics.But, entered on short column and long column
The operation such as miscellaneous is still carried out successively after miscellaneous, elution target compound and elution before capable loading, elution, takes still longer, production
The space that can be lifted is limited.
Aumann etc.（United States Patent (USP) 8496836,2013）A multiple column system is built, system is divided into 5 areas：Loading is removed
Qian Za areas, Disengagement zone, target compound elution zone, target compound-rear hybrid compound elution zone and rear miscellaneous elution zone.Its feature
It is that loading is except preceding miscellaneous, separation, target compound elution, target compound-rear hybrid compound elution and rear miscellaneous elution etc. are in difference
Area carry out simultaneously, the time required to reducing chromatographic process.But, in the technology, the sample into Disengagement zone is only eliminated
Miscellaneous before a large amount of, miscellaneous after not removing, the reduction to total peak width and chromatogram load is limited, to sample introduction frequency, separating capacity and production
The lifting of energy is not notable.The technical equipment is relative complex, and can not use the filler of two kinds of different stalling characteristics.
In summary, the continuous single column chromatographic method that separation field active demand sample introduction frequency is higher, separating capacity is stronger
With equipment, further to improve production capacity, reduce cost.
The content of the invention
In view of the above-mentioned problems, it is an object of the invention to provide a kind of sample introduction frequency is higher, that separating capacity is stronger is continuous
Single column chromatographic method and equipment, can further improve production capacity, reduce cost.
To achieve the above object, the present invention uses following technical scheme：Continuous chromatography system is built by branched shorter chromatogram column,
The system is divided into Liang great Qu：Crude separation area and smart Disengagement zone.Crude separation area is made up of five subprovinces：Loading area, Qu Qianza areas, go
The areas of Hou Za 1, sample elution area, the areas of Qu Houza 2, are defined as I, II, III, IV and V area successively.Smart Disengagement zone is by two subprovince groups
Into：Smart Disengagement zone and sample elution area, are defined as VI and VII area successively.Subprovince by 1~n（n=1,2,3,4,5,6 or 7）Branch color
Compose post in series, connected between chromatographic column and chromatographic column by pipeline or/and valve interface；Chromatographic process on this system
For：Many component samples are in I area's Pulsed Sampling；After single injected sampling, through valve transfer, Ith area end post carry is the first post in IIth area, in IIth area
It is miscellaneous before removing（Target compound is eluted to and just penetrates IIth area）；Through valve transfer, IIth area end post carry is the first post in IVth area, sample
Target compound is eluted to just completely into the last post in IVth area in IVth area；It is miscellaneous after being removed in III and V area；Through valve transfer, IV
Area end post carry is the first post in VIth area, and sample is finely separated in VIth area（Target compound is eluted to and just penetrates VIth area）；Through
Valve transfer, the last post carry in VIth area is the first post in VIIth area, Fractional Collections target compound is eluted in VIIth area and containing a small amount of rear miscellaneous
Target compound；The above method is realized by intelligent controls such as valve transfer, the start and stop of pump or/and flow velocity regulation and control.
In the above method provided by the present invention and its equipment, using the chromatographic column of same physical dimension.The chromatogram
A diameter of 10~2000mm of post, column diameter size directly determines the height of production capacity.The total length of each subprovince chromatographic column with
The function of each subprovince is related, is mainly determined by sample properties, filler attribute and filler particle size, and column length is closed with filler particle size in inverse ratio
System, and influenceed by homogeneity filling technology；The length of chromatographic column is 50~600mm in subprovince, and most short column length should be able to accommodate one
All target compounds in secondary applied sample amount.
In the above method provided by the present invention and its equipment, the chromatographic column can all load same filler, also may be used
A kind of chromatographic column in filler, smart Disengagement zone is all loaded with the chromatographic column in crude separation area and all loads another filler, such as rough segmentation
From in area chromatographic column filling filler absorption property be：Chromatographic column loads the absorption property of filler in A ＜ B ＜ C, smart Disengagement zone
For：A ＜ C ＜ B.
In the above method provided by the present invention and its equipment, the valve is many stream rotary valves, many mouthfuls of rotations of single-flow-path
Rotary valve or/and stop valve, wherein the most succinct with many stream rotary valves.
In the above method provided by the present invention and its equipment, the connected mode between the chromatographic column is：Valve body-valve connects
Mouth-chromatographic column-valve interface-valve body-valve interface-chromatographic column-valve interface-valve body-, or valve body-valve interface-chromatographic column-pipeline-
(chromatographic column) n - pipeline-chromatographic column-valve interface-valve body-.When the connected mode of subprovince chromatographic column is：Valve body-valve interface-chromatogram
Post-pipeline-(chromatographic column) n During-pipeline-chromatographic column-valve interface-valve body, between first post and last postnBranch chromatographic column is not involved in color
Compose post circulation；NownBranch shorter chromatogram column can be substituted with an isometric long chromatographic column.
In the above method provided by the present invention and its equipment, many component samples at least include miscellaneous A before 1, after 1
Miscellaneous C and 1 target compound B totally 3 components.
In the above method provided by the present invention and its equipment, frequency and the valve transfer frequency phase of the Pulsed Sampling
Deng, sample introduction once, switching once, or switches once, and sample introduction is once.
In the above method provided by the present invention and its equipment, the mobile phase for eluting each area can be with identical, can not also phase
Together, mobile phase can be isocratic or linear, pseudo-linear or nonlinear.
The above method and its equipment provided by the present invention, can carry out a variety of adaptations according to specific separation object,
Such as：Ith area is merged with IIth area, IIIth area, VIIth area and IIth area is saved and has connecting pipe（For circulating containing a small amount of rear miscellaneous target chemical combination
Thing）, VIIth area eluted using adverse current, and crude separation area with smart Disengagement zone be configured to two sets of independent systems, two systems are led to
Cross synchronous interaction and realize separation process etc..
The present invention is due to taking above technical scheme, and it has advantages below：1st, many component samples are removed in crude separation area
After substantial amounts of pre-impurity and post-impurity, then finely separated through smart Disengagement zone, thus significantly reduce smart Disengagement zone chromatogram load
With total peak width, enhance chromatogram separating capacity, improve sample introduction frequency, improve production capacity；2nd, crude separation area and smart Disengagement zone
Each chromatographic process carried out simultaneously in each different subprovince, reduce further chromatographic process required time, improve production capacity；
3rd, the crude separation area filler different with the usable unbundled attribute in smart Disengagement zone, can further lift the separating capacity of chromatogram.
, can the invention provides a kind of continuous single column chromatographic method that sample introduction frequency is higher, separating capacity is stronger and equipment
Further improve production capacity, reduce cost, the practical demand of separation field can be met.
Brief description of the drawings
Fig. 1 is method provided by the present invention and its structure and the principle schematic of chromatographic process of equipment；
Fig. 2 is the signal of the structure and chromatographic process of the filling system of -12 post of 10 7 stream rotary valves provided by the present invention -1
Figure；
Fig. 3 is the signal of the structure and chromatographic process of the filling system of -12 post of 12 7 stream rotary valves provided by the present invention -2
Figure；
Fig. 4 is the structure of the filling system of -8 post of 86 stream rotary valves provided by the present invention -2 and the schematic diagram of chromatographic process；
Fig. 5 is single-flow-path rotary valve provided by the present invention（End valve group）The structure of the filling system of -8 post -2 and chromatographic process
Schematic diagram；
Fig. 6 is single-flow-path rotary valve provided by the present invention（End valve group）The structure and chromatographic process of the filling system of -12 post -1
Schematic diagram；
Fig. 7 is single-flow-path rotary valve provided by the present invention-structure of the filling system of the post of stop valve-12-1 and showing for chromatographic process
It is intended to.
Embodiment
The present invention is described in detail with reference to the accompanying drawings and examples.
Embodiment one
As shown in figure 1, the change system that the present embodiment is provided is by 1 12 7 stream rotary valves, 12 same fillers of filling
Chromatographic column, 7 pumps, 2 detectors and 1 collector build, the system is divided into Liang great Qu：Crude separation area and smart Disengagement zone.
Crude separation area is made up of five subprovinces：Loading area（No. 1 post）, Qu Qianza areas（2 and No. 4 posts）, the areas of Qu Houza 1（No. 3 posts）, sample
Elution zone（5 and No. 7 posts）, the areas of Qu Houza 2（No. 6 posts）, I, II, III, IV and V area is defined as successively（Dotted line frame）.Smart Disengagement zone
It is made up of two subprovinces：Smart Disengagement zone（8th, 9,10 and No. 11 posts）With sample elution area（No. 12 posts）, VI and VII are defined as successively
Area.Subprovince is made up of 1~4 Coupled columns, is connected between chromatographic column and chromatographic column by pipeline by the interface of valve.7
Pump independently conveys many component sample liquid F and 6 kinds of mobile phase S2~S7.6 kinds of mobile phases can be completely or partially identical, can also be complete
It is complete different；Mobile phase can be isocratic or linear, pseudo-linear or nonlinear.The II column outlet end of area 4 and detection
Device is connected, with detector signal control mobile phase S2The start and stop of solution feed pump.The VI column outlet end of area 11 and detector phase
Even, the switching of rotary valve is controlled with detector signal.I area's sampling pump and IV area mobile phase S4Solution feed pump be timing start and stop control
System.The VII column outlet end of area 12 is connected with collector, and collector is controlled using timed collection.The system is suitable to many component samples
Separation.
Chromatographic process on this system is：Many component sample Fs are in I area's Pulsed Sampling, sample introduction frequency and valve transfer frequency
Rate is equal, and once, switching is once for sample introduction；After single injected sampling, through valve transfer, the I post carry of area 1 is the post of IIth area 2, in IIth area
By mobile phase S2Elution is miscellaneous before removing（Target compound is eluted to and just breaks through No. 4 posts）；Through valve transfer, II post of area 4
Carry is the post of IVth area 5, in IVth area by mobile phase S4Target compound is eluted to just completely into No. 7 posts；Through valve transfer,
The IV post carry of area 7 is the post of VIth area 8, and sample is in VIth area by mobile phase S6Elution is carried out by No. 8, No. 9, No. 10 and No. 11 posts
Fine separation（Target compound is eluted to and just penetrates No. 11）；Through valve transfer, the VI post carry of area 11 is the post of VIIth area 12,
In VIIth area by mobile phase S7Elution, and Fractional Collections target compound and contain it is a small amount of after miscellaneous target compound；In III and V
Area is respectively by mobile phase S3With mobile phase S5It is miscellaneous after removing.Stepping of the above method by rotary valve along dotted arrow direction switches
And realize, stepping stride is 30 °, and chromatographic column is circulated in 12 chromatographic columns, after such as switching first：Ith area is No. 12 posts, and IIth area is
No. 1 and No. 3 posts, IIIth area are No. 2 posts, and IVth area is No. 4 and No. 6 posts, and Vth area is No. 5 posts, and VIth area is No. 7, No. 8, No. 9 and No. 10
Post, VIIth area is No. 11 posts.On this system, each chromatographic process in crude separation area and smart Disengagement zone is carried out simultaneously in each subprovince.
Embodiment two
The present embodiment shown in Fig. 2 be equally as the system constructed by the chromatographic columns of 12 same fillers of filling, its structure with
It is essentially identical that embodiment one provides system, and chromatographic process and function provide that system is identical with embodiment one, they
Difference is：1st, the present embodiment is with 1 10 7 stream rotary valve constructing systems, and valve position is than embodiment one few 2；2nd, 4, VIth area color
Compose in post, it is middle 2（62 and 63）Connect, be placed in outside valve with first post and last post, valve position is not accounted for, be not involved in chromatographic column circulation；3、
The stepping stride of the present embodiment is 36 °.
The change system that the present embodiment is provided is characterised by：Economizing valve position can reduce rotary valve diameter；Valve is outer 2 short
Chromatographic column can be substituted with an isometric chromatographic column.
Embodiment three
As shown in figure 3, the change system that the present embodiment is provided is by 1 12 7 stream rotary valves, 12 chromatographic columns, 7 pumps, 2
Individual detector and 1 collector are built；The system is divided into Liang great Qu：Crude separation area and smart Disengagement zone.Crude separation area is by five Asias
District's groups into：Loading area（No. 1 post）, Qu Qianza areas（2 and No. 4 posts）, the areas of Qu Houza 1（No. 3 posts）, sample elution area（5 and 1 ' number
Post）, the areas of Qu Houza 2（No. 6 posts）, I, II, III, IV and V area is defined as successively（Dotted line frame）.Smart Disengagement zone is by two subprovince groups
Into：Smart Disengagement zone（2 ', 3 ', 4 ' and 5 ' numbers posts）With sample elution area（6 ' numbers posts）, VI and VII area is defined as successively.Subprovince is by 1
~4 Coupled columns are constituted, and are connected between chromatographic column and chromatographic column by pipeline by the interface of valve.7 pumps are independently conveyed
Many component sample liquid F and 6 kinds of mobile phase S2~S7.6 kinds of mobile phases can be completely or partially identical, can also be entirely different；Flowing
Can be mutually isocratic or linear, pseudo-linear or nonlinear.The II column outlet end of area 4 is connected with detector, to examine
Survey device signal control mobile phase S2The start and stop of solution feed pump.The VI column outlet end of area 5 ' is connected with detector, with detector
Signal controls the switching of rotary valve.I area's sampling pump and IV area mobile phase S4Solution feed pump be timing start-up and shut-down control.VII post of area 6 '
The port of export is connected with collector, and collector is controlled using timed collection.The system is suitable to the separation of many component samples.
Chromatographic process on this system is：Many component sample Fs are in I area's Pulsed Sampling, sample introduction frequency and valve transfer frequency
Rate is equal, and once, switching is once for sample introduction；After single injected sampling, through valve transfer, the I post carry of area 1 is the post of IIth area 2, in IIth area
By mobile phase S2Elution is miscellaneous before removing（Target compound is eluted to and just breaks through No. 4 posts）；Through valve transfer, II post of area 4
Carry is the post of IVth area 5, in IVth area by mobile phase S4Target compound is eluted to just completely into 1 ' number post；Cut through valve
Change, the IV post carry of area 1 ' is the post of VIth area 2 ', and sample is in VIth area by mobile phase S6Elution passes through 2 ' numbers, 3 ' numbers, 4 ' numbers and 5 '
Number post is finely separated（Target compound is eluted to and just penetrates 5 ' numbers）；Through valve transfer, the VI post carry of area 5 ' is VII
The post of area 6 ', in VIIth area by mobile phase S7Elution, and Fractional Collections target compound and contain it is a small amount of after miscellaneous target compound；
In III and V area respectively by mobile phase S3With mobile phase S5It is miscellaneous after removing.The above method is by rotary valve along dotted arrow direction
Stepping switches and realized, stride is 60 °.After switching first：Ith area is No. 6 posts, and IIth area is No. 1 and No. 3 posts, and IIIth area is No. 2
Post, IVth area is No. 4 and 6 ' numbers posts, and Vth area is No. 5 posts, and VIth area is 1 ' number, 2 ' numbers, 3 ' numbers and 4 ' numbers post, and VIIth area is 5 ' numbers posts.
In the system, each chromatographic process in crude separation area and smart Disengagement zone is carried out simultaneously in each subprovince.
The present embodiment provides chromatographic column number and system operation in component, subregion, subprovince number and the subprovince of change system
Pattern is all identical with embodiment one, and their difference is：1st, the present embodiment is using 2 kinds of different fillers, and 1~No. 6 post is a kind of
Filler, 1 '~6 ' numbers another fillers of post；2nd, the chromatographic column of two kinds of different fillers distributes alternately；3rd, the stepping step of the present embodiment
Width is 60 °.The present embodiment provides change system and is characterised by：The circulation of chromatographic column is carried out only on filler identical post.
Example IV
As shown in figure 4, the change system that the present embodiment is provided is by 186 stream rotary valves, 8 chromatographic columns（2 kinds of filling is not
Same filler, a kind of 1~No. 4 filler of post, 1 '~4 ' numbers another fillers of post）, 6 pumps, 2 detectors and 1 collection
Device is built；The system is divided into Liang great Qu：Crude separation area and smart Disengagement zone.Crude separation area is made up of five subprovinces：Loading area（No. 1
Post）, Qu Qianza areas（No. 2 posts）, sample elution area（3 and 1 ' number post）, Qu Houza areas（No. 4 posts）, I, II, III and is defined as successively
IVth area（Dotted line frame）.Smart Disengagement zone is made up of two subprovinces：Smart Disengagement zone（2 ' and 3 ' numbers posts）With sample elution area（4 ' numbers posts）,
V and VI area is defined as successively.Subprovince is made up of 1~2 Coupled columns, and valve is passed through by pipeline between chromatographic column and chromatographic column
The interface connection of door.6 pumps independently convey many component sample liquid F and 5 kinds of mobile phase S2~S6.5 kinds of mobile phases can whole or portion
Split-phase is same, can also be entirely different；Mobile phase can be isocratic or linear, pseudo-linear or nonlinear.II area 2
Number column outlet end is connected with detector, with detector signal control mobile phase S2The start and stop of solution feed pump.V post of area 3 '
The port of export is connected with detector, and the switching of rotary valve is controlled with detector signal.I area's sampling pump and III area mobile phase S3Feed flow
Pump is timing start-up and shut-down control.The VI column outlet end of area 4 ' is connected with collector, and collector is controlled using timed collection.The system is fitted
It is few or without rear miscellaneous sample separation in rear miscellaneous amount（Sample typically Jing Guo SMB crude separation, or passed through again after displcement chromatography preliminary purification
Sample after the non-chromatographic technique processing such as crystallization）.
Chromatographic process on this system is：Many component sample Fs are cut in the post Pulsed Sampling of Ith area 1, sample introduction frequency with valve
Change frequency equal, once, switching is once for sample introduction；After single injected sampling, through valve transfer, the I post carry of area 1 is the post of IIth area 2,
IIth area is by mobile phase S2Elution is miscellaneous before removing（Target compound is eluted to and just breaks through No. 2 posts）；Through valve transfer, II area 2
Number post carry is the post of IIIth area 3, in IIIth area by mobile phase S3Target compound is eluted to just completely into 1 ' number post；Through valve
Switching, the III post carry of area 1 ' is the post of Vth area 2 ', and sample is in Vth area by mobile phase S5Elution passes through 2 ' numbers and 3 ' numbers posts are carried out
Fine separation（Target compound is eluted to and just penetrates 3 ' numbers posts）；Through valve transfer, the V post carry of area 3 ' is VIth area 4 '
Post, in VIth area by mobile phase S6Elution, and Fractional Collections target compound and contain it is a small amount of after miscellaneous target compound；IV by
Mobile phase S4Elution is miscellaneous after removing.
Stepping of the above method by rotary valve along dotted arrow direction switches and realized, stride is 90 °, chromatographic column circulation
Carried out only on filler identical post.After switching first：Ith area is No. 4 posts, and IIth area is No. 1 post, and IIIth area is No. 2 and 4 ' numbers posts,
IVth area is No. 3 posts, and Vth area is 1 ' number and 2 ' numbers posts, and VIth area is 3 ' numbers posts.On this system, crude separation area and smart Disengagement zone are assorted
Spectrum process is carried out simultaneously in each subprovince.
Embodiment five
The present embodiment is built and example IV identical system by many mouthfuls of rotary valves of stop valve or a kind of single-flow-path.The present embodiment
The component of the chromatographic system provided is：8 chromatographic columns（2 kinds of different fillers of filling, a kind of 1~No. 4 filler of post, 1 '~
Another filler of 4 ' numbers posts）, 6 pumps, 2 detectors and 1 collector, stop valve 60,12 5 lead to, and 44 lead to, or 12
Only 4 enter 1 and go out rotary valve and 43 are entered 1 and go out rotary valve；I.e. with 60 stop valves, 12 5 it is logical and 44 it is logical, or 12 4 entered 1 and go out rotation
Rotary valve and 43 enter the 1186 stream rotary valves gone out in rotary valve alternate embodiment four.60 stop valves, 12 it is 5 logical and 4
Part, which can build 4 and enter 1, to be gone out（Also it can be considered that 1 enters 4 and goes out）12 groups of valve valve group, 3, which enter 1, goes out（Also it can be considered that 1 enters 3 and goes out）4 groups of valve valve group.4 enter 1
Go out valve valve group and 3 to enter 1 and go out valve valve group to enter 1 with 4 respectively and go out rotary valve and 3 to enter 1 to go out rotary valve function phase same.
Above-mentioned component can the chromatographic system that is provided of construction cost embodiment, the function and chromatographic process of the system by Fig. 5
Identical with apply that example four provided, it, which is distinguished, is that switching method is different：1st, the chromatographic system that the present embodiment is provided is to pass through
The "ON" " closing " of stop valve, which is realized, opens overall stepping 1 from right to left of state valve in switching, such as Fig. 5, just realize sub- chromatographic column
Stepping switching；2nd, the chromatographic system that the present embodiment is provided can be considered two sets of independent systems, and two systems pass through synchronous
It is dynamic to realize separation process.
Embodiment six
The present embodiment is built and the identical system of embodiment one by many mouthfuls of rotary valves of stop valve or a kind of single-flow-path.The present embodiment
The component of the chromatographic system provided is：12 chromatographic columns（Load filler of the same race）, 7 pumps, 2 detectors and 1 collection
Device, stop valve 192,12 8 lead to, and 12 10 lead to, or 12 7 are entered 1 and go out rotary valve and 12 1 are entered 9 and go out rotary valve；I.e. with 192
Stop valve, 12 8 it is logical and 12 10 it is logical, or 12 7 entered 1 and go out rotary valve and 12 1 are entered 9 and gone out in rotary valve alternate embodiment one
1 12 7 stream rotary valves.192 stop valves, 12 8 it is logical and 12 10 it is logical, 7 can be built enter 1（Also it can be considered that 1 enters 7
Go out）12 groups of valve valve group, 1, which enters 9, goes out（Also it can be considered that 9 enter 1 and go out）12 groups of valve valve group.7 enter 1 go out valve valve group and 1 enter 9 go out valve valve group difference
Enter 1 with 7 and go out rotary valve and 1 to enter 9 to go out rotary valve function phase same.
The chromatographic system provided by above-mentioned component by Fig. 6 construction cost embodiments, the function and chromatographic process of the system
Identical with apply that example one provided, it, which is distinguished, is that switching method is different：The chromatographic system that the present embodiment is provided is by cutting
Only the "ON" " closing " of valve, which is realized, opens overall stepping 1 from right to left of state valve in switching, such as Fig. 6, just realize sub- chromatographic column
Stepping switches.
Embodiment seven
The present embodiment is built and the identical system of embodiment one by many mouthfuls of rotary valves of another single-flow-path.The present embodiment is provided
The component of chromatographic system be：12 chromatographic columns（Load filler of the same race）, 7 pumps, 2 detectors and 1 collector, 14
12 enter 1 go out rotary valve, 24 13 it is logical and 12 2 enter 1 and go out valve；I.e. with 14 12 enter 1 go out rotary valve, 24 13 it is logical and 12 2 enter 1
The 1 12 7 stream rotary valves gone out in valve alternate embodiment one.
Entering 1 for 7 12, to go out rotary valve logical in parallel with position by same sequence with 12 13（No. 1 position such as 7 valves connects from left to right
Mouth presses F, S2、S3、S4、S5、S6、S7Order it is logical in parallel with one 13, No. 2 positions of 7 valves from left to right interface by F, S2、S3、
S4、S5、S6、S7Order it is logical in parallel with second 13）, by 84 path in parallel, 12 paths of 7 valves, constitute one big valve
Group.Enter 1 for 14 12 and go out that rotary valve and 24 13 are logical can be built into 2 big valve group.
2 big valve group, 12 2 enter 1 go out valve and above-mentioned other components just can the color that is provided of construction cost embodiment by Fig. 7
Spectra system.The function and chromatographic process of the chromatographic system are identical with apply that example one provided, and it, which is distinguished, is that switching method is different：
The chromatographic system that the present embodiment is provided is to realize to open state valve entirety in switching, such as Fig. 7 by the "ON" " closing " of stop valve
Stepping 1, just realizes the stepping switching of sub- chromatographic column from right to left.
The present invention is only illustrated with above-described embodiment, the structure of equipment provided by the present invention and the embodiment party of chromatographic process
Method can be all varied from.It is all equipment to be built according to the principle of the invention and real on the basis of technical solution of the present invention
Improvement or equivalents that applying method is carried out, should not be excluded outside protection scope of the present invention.
Claims (10)
1. the method and its equipment of a kind of continuous chromatography, it is characterised in that：It is described to be equipped for multicolumn continuous chromatography system, the system
System is divided into Liang great Qu：Crude separation area and smart Disengagement zone；The crude separation area is made up of five subprovinces：Loading area, Qu Qianza areas, go
The areas of Hou Za 1, sample elution area, the areas of Qu Houza 2, are defined as I, II, III, IV and V area successively；The smart Disengagement zone is by two Asias
District's groups into：Smart Disengagement zone and sample elution area, are defined as VI and VII area successively；The subprovince is by 1~n（n =1、2、3、4、5、6
Or 7）Branch Coupled columns are constituted, and are connected between chromatographic column and chromatographic column by pipeline or/and valve interface；Methods described is：It is many
Component sample is in I area's Pulsed Sampling；After single injected sampling, through valve transfer, Ith area end post carry is the first post in IIth area, in the flowing of IIth area
Mutually elution is miscellaneous before removing（Target compound is eluted to and just penetrates IIth area）；Through valve transfer, IIth area end post carry is that IVth area is first
Target compound, is eluted to just completely into the last post in IVth area by post in IV area's mobile phase；Removed in III and V area's mobile phase elution
It is miscellaneous afterwards；Through valve transfer, IVth area end post carry is the first post in VIth area, and sample is finely separated in VIth area（Mobile phase is by targeted
Compound, which is eluted to, just penetrates VIth area）；Through valve transfer, VIth area end post carry is the first post in VIIth area, in the mobile phase elution segmentation of VIIth area
Collect target compound and containing a small amount of rear miscellaneous target compound；Methods described passes through valve transfer, the start and stop of pump or/and stream
The intelligent controls such as velocity modulation control are realized.
2. the method as described in claim 1 and its equipment, it is characterised in that：The chromatographic column is all same physical dimension, directly
Footpath is 10~2000mm, and length is 50~600mm.
3. the method as described in claim 1 and its equipment, it is characterised in that：What the chromatographic column was all loaded is same fill out
Material.
4. the method as described in claim 1 and its equipment, it is characterised in that：What chromatographic column was all loaded in the crude separation area is
What chromatographic column was all loaded in same filler, the smart Disengagement zone is another filler.
5. the method as described in claim 1 and its equipment, it is characterised in that：The valve is many stream rotary valves, single-flow-path
Many mouthfuls of rotary valves or/and stop valve.
6. the method as described in claim 1 and its equipment, it is characterised in that：Connected mode between the chromatographic column is：Color
Compose post-valve interface-valve body-valve interface-chromatographic column, or chromatographic column-pipeline-chromatographic column.
7. the method as described in claim 1 and its equipment, it is characterised in that：Mobile phase used in the elution be it is isocratic or/
With gradient.
8. method and its equipment as described in claim 1 and 6, it is characterised in that：Gradient mobile phase used in the elution is
Linearly, pseudo-linear or/and nonlinear.
9. the method as described in claim 1 and its equipment, it is characterised in that：The frequency of described Pulsed Sampling and the switching of valve
Frequency is equal.
10. the method as described in claim 1 and its equipment, it is characterised in that：Described crude separation area and smart Disengagement zone can structures
Two sets of independent systems are built up, separation process is realized by the series connection linkage of this two systems.
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Cited By (1)
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