CN205838893U - A kind of isolated and purified device of cyclosporin homologue - Google Patents
A kind of isolated and purified device of cyclosporin homologue Download PDFInfo
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- CN205838893U CN205838893U CN201620713866.1U CN201620713866U CN205838893U CN 205838893 U CN205838893 U CN 205838893U CN 201620713866 U CN201620713866 U CN 201620713866U CN 205838893 U CN205838893 U CN 205838893U
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Abstract
This utility model provides the isolated and purified device of a kind of cyclosporin homologue, described isolated and purified device includes a sample injector and at least isolated and purified unit of the tangential chromatographic column of two-stage, the isolated and purified unit of tangential chromatographic column at different levels include chromatographic column, eluant storage tank, compression pump, collect liquid storage tank, described compression pump is connected with eluant storage tank, described eluant storage tank is connected to chromatographic column upper end, described sample feeding device is connected to the upper end of chromatographic column, the lower end of described chromatographic column is provided with two flow exports, one of them flow export accesses collects liquid storage tank, the chromatographic column of another flow export next stage isolated and purified unit of tangential chromatographic column is connected.The separation preparation amount of this utility model cyclosporin homologue is big, and separating degree is high, it is thus achieved that target product purity high, separation process is the most convenient, be suitable for automated production.
Description
[technical field]
This utility model relates to the isolated and purified device of a kind of cyclosporin homologue.
[background technology]
Cyclosporin be 20 century 70s find by Beauveria nivea, (beauveria bassiana, original name is many
Hole trichoderma tolypocladium inflatum) one group of ring-type 11 peptide material producing.One of them key component--
Ciclosporin A is widely used in transplant operation as efficient immunosuppressant.Its appearance causes filed of organ transplantation
One revolution.In addition to immunosuppressive action, ciclosporin also has other biological activity a series of, such as treatment lupus erythematosus, psoriasis
Deng autoimmune pathologies, suppression HIV-1 virus, reverse multiple drug resistance of tumor etc..
From Beauveria nivea, it has been separated to the homologue of more than 20 cyclosporin at present, and in the generation of up to 17 kinds of funguses
Thank and product is separated to various cyclosporins.Industrial the fermentable such as Beauveria nivea is generally utilized to produce ring
Spore element A, is often accompanied with different types of impurity during the fermentation, including producing more than 20 the similar homology of structural property
Thing, existing isolated and purified device, the single tangential chromatographic column of many employings carries out sample separation with conversion solvent ratios, but this
There is following drawback in separate mode.
(1) separating for the cyclosporin homologue that polarity is close, use single chromatography column apparatus, applied sample amount is little, or
Being to need longer height and diameter proportion, can be only achieved separating effect, this is increased by the cost of industrial mass production.
(2), in order to obtain highly purified cyclosporin homologue, use single chromatography column apparatus to separate, need repeated collection,
Sample introduction, separation, cause that operating procedure is numerous and diverse, the operating time is long, causes some component damages of degrading.
[summary of the invention]
The technical problems to be solved in the utility model, is to provide the isolated and purified device of a kind of cyclosporin homologue,
It is big to the separation preparation amount of cyclosporin homologue, and separating degree is high, it is thus achieved that target product purity high, separation process is the most just
Automated production prompt, applicable.
This utility model is achieved in that
A kind of isolated and purified device of cyclosporin homologue, described isolated and purified device include a sample injector and
At least isolated and purified unit of the tangential chromatographic column of two-stage, the isolated and purified unit of tangential chromatographic column at different levels include that chromatographic column, eluant store up
Tank, compression pump, collection liquid storage tank, described compression pump is connected with eluant storage tank, and described eluant storage tank is connected on chromatographic column
End, described sample feeding device is connected to the upper end of chromatographic column, and the lower end of described chromatographic column is provided with two flow exports, one of them
Flow export accesses collects liquid storage tank, and the chromatographic column of another flow export next stage isolated and purified unit of tangential chromatographic column is connected.
Further, described eluant storage tank is provided with one first on-off valve, described sample in the connecting tube of chromatographic column
Being provided with one second on-off valve below product injector, the flow export being connected with collection liquid storage tank is provided with the 3rd on-off valve,
The flow export being connected with next stage chromatographic column is provided with the 4th on-off valve.
Further, the height of described chromatographic column and internal diameter are than for 10:1～20:1.
Further, the packing layer of described chromatographic column is silica gel or acidic alumina packing layer.
Further, the particle diameter of described chromatographic column packing layer reduces step by step.
The utility model has the advantage of:
This utility model is the tangential chromatographic column combined separation and purification device of a kind of plural serial stage, and the sample of first order post enters
Sample device single injected sampling, every one-level has the blood circulation of independent driving, can individually control, and arranging chromatographic column according to actual needs can fill
Fill out different filler, also or same packing material size can reduce step by step；Chromatographic column lower ends at different levels are provided with two flow exports, each outflow
Mouth is both provided with on-off valve, according to the purity of effluent compound, accesses sample collection liquid storage tank or accesses subordinate's chromatographic column
Separate further.
Cyclosporin homologue can be efficiently separated and purification by this utility model rapidly, and applied sample amount increases,
Can realize single injected sampling, multistage chromatography, collect different cyclosporin homologue, sample loss amount is little, and can work continuously, subtracts
Few operating time, improve work efficiency；It addition, it is big to the separation preparation amount of cyclosporin homologue, separating degree is high, it is thus achieved that
Target product purity is high, and separation process is the most convenient, be suitable for automated production.
[accompanying drawing explanation]
This utility model is further described the most in conjunction with the embodiments.
Fig. 1 is the structural representation of the isolated and purified device of this utility model a kind of cyclosporin homologue.
Fig. 2 is the HPLC-UV detection of this utility model embodiment cyclosporin homologue sample solution.
[detailed description of the invention]
Refer to shown in Fig. 1 and Fig. 2, embodiment of the present utility model is described in detail.
As it is shown in figure 1, the isolated and purified device of a kind of cyclosporin homologue involved by this utility model, described separation
Purification devices includes a sample injector 1 and at least isolated and purified unit of the tangential chromatographic column of two-stage 2, and tangential chromatographic columns at different levels divide
Be connected with each other between purification unit 2, the isolated and purified unit of tangential chromatographic column 2 at different levels include chromatographic column 21, eluant storage tank 22,
Compression pump 23, collection liquid storage tank 24, described compression pump 23 is connected with eluant storage tank 22, and described eluant storage tank 22 is connected to layer
Analysis post 21 upper end, described sample feeding device 1 is connected to the upper end of chromatographic column 21, and the lower end of described chromatographic column 21 is provided with two streams
Outlet 25, one of them flow export 25 accesses collects liquid storage tank 24, and another flow export 25 tangential chromatographic column of next stage separates pure
The chromatographic column 21 changing unit 2 is connected.
Described eluant storage tank 22 is provided with one first on-off valve 26 in the connecting tube of chromatographic column 21, and described sample enters
Being provided with one second on-off valve 27 below sample device 1, the flow export 25 being connected with collection liquid storage tank 24 is provided with the 3rd on-off valve
Door 28, the flow export 25 being connected with next stage chromatographic column 21 is provided with the 4th on-off valve 29 and one the 5th on-off valve 30,
Described 4th on-off valve 29 is near flow export 25, and described 5th on-off valve 30 is near next stage chromatographic column 21.
The height of described chromatographic column 21 and internal diameter are than for 10:1～20:1.
The packing layer of described chromatographic column 21 is silica gel or acidic alumina packing layer.
The particle diameter of described chromatographic column 21 packing layer reduces step by step.
Shown in specifically used mode below embodiment of the present utility model:
Respectively 200-300 mesh silica gel 200L dry method is loaded one-level chromatographic column 21,300-400 mesh silica gel 200L dry method loads
Two grades of chromatographic columns 21, chromatograph the height of 21 posts and internal diameter than for 10:1；Take 2 kilograms of cyclosporin dissolving crude products in proper amount of acetone,
Filter, load sample feeding device 1, open the second on-off valve 27, close the first on-off valve 26, single injected sampling；Sample introduction is complete,
Closing the second on-off valve 27, open the first on-off valve 26, eluant storage tank 22, equipped with petroleum ether, starts compression pump 23, will
Petroleum ether pumps into chromatographic column 21, opens the 3rd on-off valve 28, closes the 4th on-off valve 29, after 1 times of column volume of eluting, uses instead
Acetone: petroleum ether (1:8) eluting, fraction collection, collect the efficient Liquid Detection of liquid, (purity is more than to collect Cyclosporin D successively
95%), CYCLOSPORIN G (purity is more than 95%)；Collect complete to CYCLOSPORIN G, when detection has cyclosporin A to occur, use instead
Acetone: petroleum ether (1:7) eluting, closes the 3rd on-off valve 28, opens the 4th on-off valve 29 and the 5th on-off valve 30, make
Eluent proceeds to the next stage isolated and purified unit of tangential chromatographic column 2；Timing simultaneously detects the eluent of one-level chromatographic column 21, works as inspection
When survey does not has cyclosporin A, close the 4th on-off valve 29 and the 5th on-off valve 30, the isolated and purified lists of tangential chromatographic column at different levels
Unit 2 will individually control.The isolated and purified unit of the tangential chromatographic column of one-level 2 uses acetone instead: petroleum ether (1:6) eluting, branch receives
Collection, collects the efficient Liquid Detection of liquid, collects Ala2-cyclosporine (purity is more than 95%) successively, and (purity is more than cyclosporin E
90%), cyclosporins C (purity is more than 95%)；Two grades of tangential chromatographic column isolated and purified unit 2 blood circulation alone, single
Solely control, eluant acetone: petroleum ether (1:7) eluting, fraction collection, collect the efficient Liquid Detection of liquid, collect ring spore bacterium successively
Element T (purity is more than 95%), Cyclosporin H (purity is more than 95%), cyclosporin A (purity is more than 98%).
Owing to have employed said structure, it is to avoid existing Conventional chromatography device, the problem that applied sample amount is little, can shorten simultaneously
Preparation time, reduces the usage amount of solvent；Under conditions of identical applied sample amount, the purity of each homologue is significantly increased, pure group
Yield is divided to improve 5～15%；Existing Conventional chromatography device, it is impossible to first use difference filler, for homologue polarity extremely
Close to the separation of compound, need to carry out secondary the most repeatedly column chromatography for separation, need repeated collection, sample introduction, separation, cause behaviour
Make that step is numerous and diverse, the operating time is long, cause some component damages of degrading.Have employed said structure separation cyclosporin homology
Thing, the cyclosporin T that middle polarity and polarity are very close to, Cyclosporin H, cyclosporin A fitting through one-level chromatographic column
Degree separates, and pumps into two grades of chromatographic columns and uses thinner filler again to separate, it is possible to obtain optimal preparation effect.
Referring to shown in Fig. 2, the eluate that above-described embodiment eluting obtains uses HPLC detection, and HPLC testing conditions is:
C18 chromatographic column；Volume ratio be (430:520:50:1) acetonitrile-water-t-butyl methyl ether-phosphoric acid for flowing phase, detect wavelength
210nm, temperature 70 C.
This utility model is big to the separation preparation amount of cyclosporin homologue, and separating degree is high, it is thus achieved that target product purity
Height, separation process is the most convenient, be suitable for automated production.And the target product purity height obtained after purifying, the present invention fits simultaneously
Close automated production, there is the highest economic benefit.
Although the foregoing describing detailed description of the invention of the present utility model, but those familiar with the art should
Working as understanding, our described specific embodiment is merely exemplary rather than for the limit to scope of the present utility model
Fixed, those of ordinary skill in the art, in the equivalent modification made according to spirit of the present utility model and change, should
Contain in scope of the claimed protection of the present utility model.
Claims (5)
1. the isolated and purified device of a cyclosporin homologue, it is characterised in that: described isolated and purified device includes a sample
The isolated and purified unit of the tangential chromatographic column of injector and at least two-stage, the isolated and purified unit of tangential chromatographic column at different levels include chromatography
Post, eluant storage tank, compression pump, collection liquid storage tank, described compression pump is connected with eluant storage tank, and described eluant storage tank connects
To chromatographic column upper end, described sample feeding device is connected to the upper end of chromatographic column, and the lower end of described chromatographic column is provided with two outflows
Mouthful, one of them flow export accesses collects liquid storage tank, the layer of another flow export next stage isolated and purified unit of tangential chromatographic column
Analysis post is connected.
The isolated and purified device of a kind of cyclosporin homologue the most as claimed in claim 1, it is characterised in that: described eluant
Storage tank is provided with one first on-off valve in the connecting tube of chromatographic column, is provided with one second break-make below described sample feeding device
Valve, the flow export being connected with collection liquid storage tank is provided with the 3rd on-off valve, on the flow export being connected with next stage chromatographic column
It is provided with the 4th on-off valve.
The isolated and purified device of a kind of cyclosporin homologue the most as claimed in claim 1, it is characterised in that: described chromatographic column
Height and internal diameter than for 10:1～20:1.
The isolated and purified device of a kind of cyclosporin homologue the most as claimed in claim 3, it is characterised in that: described chromatographic column
Packing layer be silica gel or acidic alumina packing layer.
The isolated and purified device of a kind of cyclosporin homologue the most as claimed in claim 4, it is characterised in that: described chromatographic column
The particle diameter of packing layer reduces step by step.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201620713866.1U CN205838893U (en) | 2016-07-08 | 2016-07-08 | A kind of isolated and purified device of cyclosporin homologue |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201620713866.1U CN205838893U (en) | 2016-07-08 | 2016-07-08 | A kind of isolated and purified device of cyclosporin homologue |
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| CN205838893U true CN205838893U (en) | 2016-12-28 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108148118A (en) * | 2017-12-12 | 2018-06-12 | 陈秀明 | A kind of isolation and purification method of Cyclosporin H |
| CN114072217A (en) * | 2019-06-28 | 2022-02-18 | 信达生物制药(苏州)有限公司 | Combined chromatography device, seamless connection chromatography method and biological agent purification method |
-
2016
- 2016-07-08 CN CN201620713866.1U patent/CN205838893U/en active Active
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108148118A (en) * | 2017-12-12 | 2018-06-12 | 陈秀明 | A kind of isolation and purification method of Cyclosporin H |
| CN114072217A (en) * | 2019-06-28 | 2022-02-18 | 信达生物制药(苏州)有限公司 | Combined chromatography device, seamless connection chromatography method and biological agent purification method |
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