CN219539494U - Micafungin mother nucleus FR179642 column chromatography system - Google Patents
Micafungin mother nucleus FR179642 column chromatography system Download PDFInfo
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- CN219539494U CN219539494U CN202320600445.8U CN202320600445U CN219539494U CN 219539494 U CN219539494 U CN 219539494U CN 202320600445 U CN202320600445 U CN 202320600445U CN 219539494 U CN219539494 U CN 219539494U
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Abstract
The utility model provides a micafungin mother nucleus FR179642 column chromatography system, which comprises a small chromatography column and a large chromatography column; the inlet of the small chromatographic column is respectively connected with the outlets of the feeding tank and the regenerant tank through a pipeline, the inlet of the small chromatographic column is also connected with a deionized water pipe I, and the outlet of the small chromatographic column is respectively connected with the inlet of the waste liquid tank and the inlet of the large chromatographic column through a pipeline; the inlet of the large chromatographic column is respectively connected with the outlets of the charging tank, the regenerant tank and the eluent tank through pipelines, the inlet of the large chromatographic column is also connected with a deionized water pipe II, and the outlet of the large chromatographic column is respectively connected with the inlets of the waste liquid tank and the eluent storage tank through pipelines; and the ion water pipe I, the deionized water pipe II and each pipeline are connected with a control valve. The transmittance of the eluent detection solution prepared by the system is 90.3%, the transmittance of the comparative single-column eluent is 22.3%, and the pigment of the eluent is greatly reduced, so that the subsequent purification production process is facilitated.
Description
Technical Field
The utility model relates to the field of separation and purification of biopharmaceuticals, in particular to a micafungin mother nucleus FR179642 column chromatography system.
Background
In the field of separation and purification of biopharmaceuticals, resin column chromatography separation technology is a common and very important means. In the traditional resin column chromatography, single column separation is adopted, and in the process of loading fermentation filtrate into a column, the resin adsorbs a great amount of fermentation byproducts such as pigment, protein, polysaccharide and the like while adsorbing the products. In the subsequent elution process, the byproducts are eluted together with the product, so that the impurity content of the byproducts in the eluent is high, and the purification effect is not ideal.
The micafungin mother nucleus FR179642 is a fermentation conversion product of the genus coleophomax (coleopomasp.), and is the most important raw material for synthesizing the antifungal drug micafungin. Chinese patents CN102952178, CN106518980, CN106755221, etc. adopt macroporous resin column single column separation and purification, the product purification effect is better, but there is the problem that pigment is too deep, which is unfavorable for the production of subsequent procedures.
Disclosure of Invention
The utility model provides a micafungin mother nucleus FR179642 column chromatography system, which solves the problems that the existing micafungin mother nucleus FR179642 adopts macroporous resin column single column separation and purification, and the pigment is too deep and is unfavorable for the subsequent procedures.
The technical scheme of the utility model is realized as follows:
a micafungin mother nucleus FR179642 column chromatography system comprises a charging tank, a regenerant tank, an eluent tank, a small chromatographic column, a large chromatographic column, a waste liquid tank and an eluent storage tank; the inlet of the small chromatographic column is respectively connected with the outlets of the feeding tank and the regenerant tank through a pipeline, the inlet of the small chromatographic column is also connected with a deionized water pipe I, and the outlet of the small chromatographic column is respectively connected with the inlet of the waste liquid tank and the inlet of the large chromatographic column through a pipeline; the inlet of the large chromatographic column is respectively connected with the outlets of the charging tank, the regenerant tank and the eluent tank through pipelines, the inlet of the large chromatographic column is also connected with a deionized water pipe II, and the outlet of the large chromatographic column is respectively connected with the inlets of the waste liquid tank and the eluent storage tank through pipelines; and the ion water pipe I, the deionized water pipe II and each pipeline are connected with a control valve.
Further, the volume ratio of the small chromatographic column to the large chromatographic column is 1:4-1:5.
Further, the control valve is an automatic control valve.
Further, the charging tank is used for charging fermentation filtrate; the regenerant tank is used for containing regenerant; the eluent tank is used for containing eluent.
Further, the feeding tank is connected with an inlet of the small chromatographic column through a first discharging pipe, and a first control valve is connected to the first discharging pipe; the outlet of the regenerant tank is connected with a first discharging main pipe, the first discharging main pipe is connected with a first main control valve, the first discharging main pipe is respectively connected with the inlet of the small chromatographic column and the inlet of the large chromatographic column through a second discharging pipe and a third discharging pipe, the second discharging pipe is connected with a second control valve, and the third discharging pipe is connected with a third control valve; the outlet of the eluent tank is connected with the inlet of the large chromatographic column through a fourth discharging pipe, and a fourth control valve is connected to the fourth discharging pipe; the ion water pipe I is connected with an ion water control valve I, and the ion water pipe I is connected with an ion water control valve II; the outlet of the small chromatographic column is connected with the inlet of the waste liquid tank through a fifth discharge pipe, a fifth control valve is connected to the fifth discharge pipe, the outlet of the small chromatographic column is connected with the inlet of the large chromatographic column through a sixth discharge pipe, and a sixth control valve is connected to the sixth discharge pipe; the outlet second discharging main pipe of the large chromatographic column is connected with a second main control valve, the second discharging main pipe is connected with the inlet of the waste liquid tank and the inlet of the eluent storage tank through a seventh discharging pipe and an eighth discharging pipe, the seventh discharging pipe is connected with a seventh control valve, and the eighth discharging pipe is connected with an eighth control valve.
The utility model has the beneficial effects that:
in the system, during the process of serially connecting fermentation filtrate to a column, impurities such as pigment, protein and the like are mainly enriched in a small chromatographic column; the micafungin mother nucleus FR179642 is mainly enriched in a large chromatographic column, after the loading is finished, the small chromatographic column contains few products, and is directly added with a regenerant for regeneration and water washing for repeated use, and the large chromatographic column is eluted by the water washing and then added with an eluent to obtain the high-purity eluent with few pigments. After the elution of the large chromatographic column is finished, adding a regenerant for regeneration and washing with water, and then repeatedly using;
the transmittance (430 nm) of the eluent detection solution prepared by the system is 90.3%, the transmittance of the contrast single-column eluent is 22.3%, and the pigment of the eluent is greatly reduced, so that the subsequent purification production process is facilitated.
Drawings
In order to more clearly illustrate the embodiments of the utility model or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, it being obvious that the drawings in the following description are only some embodiments of the utility model, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
Fig. 1 is a schematic structural view of the present utility model.
In the figure: 1-charging tank, 2-regenerant tank, 3-eluent tank, 4-small chromatographic column, 5-large chromatographic column, 6-waste liquid tank, 7-eluent storage tank, 8-first control valve, 9-second control valve, 10-first main control valve, 11-third control valve, 12-fourth control valve, 13-ionized water control valve I, 14-ionized water control valve II, 15-fifth control valve, 16-sixth control valve, 17-second main control valve, 18-seventh control valve and 19-eighth control valve.
Detailed Description
The following description of the embodiments of the present utility model will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present utility model, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the utility model without making any inventive effort, are intended to be within the scope of the utility model.
Referring to fig. 1, a micafungin mother nucleus FR179642 column chromatography system comprises a loading tank 1, a regenerant tank 2, an eluent tank 3, a small chromatographic column 4, a large chromatographic column 5, a waste liquid tank 6 and an eluent storage tank 7; the inlet of the small chromatographic column 4 is respectively connected with the outlets of the feeding tank 1 and the regenerant tank 2 through a pipeline, the inlet of the small chromatographic column 4 is also connected with a deionized water pipe I, and the outlet of the small chromatographic column 4 is respectively connected with the inlet of the waste liquid tank 6 and the inlet of the large chromatographic column 5 through a pipeline; the inlet of the large chromatographic column 5 is respectively connected with the outlets of the feeding tank 1, the regenerant tank 2 and the eluent tank 3 through pipelines, the inlet of the large chromatographic column 5 is also connected with a deionized water pipe II, and the outlet of the large chromatographic column 5 is respectively connected with the inlets of the waste liquid tank 2 and the eluent storage tank 3 through pipelines; and the ion water pipe I, the deionized water pipe II and each pipeline are connected with a control valve.
Wherein the control valve can be an automatic control valve, and concretely can be an electromagnetic control valve.
Wherein the feeding tank 1 is used for containing fermentation filtrate; the regenerant tank 2 is used for containing regenerant, and can be sodium hydroxide solution; the eluent tank 3 is used for containing eluent, in particular, the eluent can be ethanol water solution.
In some embodiments, the volume ratio of the small chromatographic column 4 to the large chromatographic column 5 is 1:4-1:5.
In some embodiments, the charging tank is connected with the inlet of the small chromatographic column 4 through a first discharging pipe 1, and a first control valve 8 is connected to the first discharging pipe; the outlet of the regenerant tank 2 is connected with a first discharging main pipe, the first discharging main pipe is connected with a first main control valve 10, the first discharging main pipe is respectively connected with the inlet of the small chromatographic column 4 and the inlet of the large chromatographic column 5 through a second discharging pipe and a third discharging pipe, the second discharging pipe is connected with a second control valve 9, and the third discharging pipe is connected with a third control valve 11; the outlet of the eluent tank 3 is connected with the inlet of the large chromatographic column 5 through a fourth discharging pipe, and a fourth control valve 12 is connected to the fourth discharging pipe; the ion water pipe I is connected with an ion water control valve I13, and the ion water pipe I is connected with an ion water control valve II14; the outlet of the small chromatographic column 4 is connected with the inlet of the waste liquid tank through a fifth discharging pipe, a fifth control valve 15 is connected to the fifth discharging pipe, the outlet of the small chromatographic column 4 is connected with the inlet of the large chromatographic column 5 through a sixth discharging pipe, and a sixth control valve 16 is connected to the sixth discharging pipe; the second discharge main pipe of the outlet of the large chromatographic column 5 is connected with a second main control valve 17, the second discharge main pipe is respectively connected with the inlet of the waste liquid tank 6 and the inlet of the eluent storage tank 7 through a seventh discharge pipe and an eighth discharge pipe, the seventh discharge pipe is connected with a seventh control valve 18, and the eighth discharge pipe is connected with an eighth control valve 19.
The application process of the utility model is as follows:
before use, adding fermentation filtrate into the feeding tank 1 according to the production process requirement; preparing sodium hydroxide solution in a regenerant tank 2; the eluent tank 3 prepares an ethanol aqueous solution.
When in use, the chromatographic system operates according to the following steps:
1. and (3) column loading adsorption: the first control valve 8, the sixth control valve 16, the second main control valve 17 and the seventh control valve 18 are opened, fermentation filtrate in the feeding tank 1 is adsorbed in series through the small chromatographic column 4 and the large chromatographic column 5, adsorption waste liquid is discharged into the waste liquid tank 6, and after the feeding is finished, the first control valve 8, the sixth control valve 16, the second main control valve 17 and the seventh control valve 18 are closed.
2. Regeneration of the small chromatographic column: after the adsorption of the upper column is finished, the small chromatographic column 4 is directly regenerated, a first main control valve 10, a second control valve 9 and a fifth control valve 15 are opened, sodium hydroxide solution in the regenerant tank 2 is added into the small chromatographic column 4 to regenerate resin, regenerated wastewater is discharged into a wastewater tank, the second control valve 9 and the first main control valve 10 are closed, an ionized water control valve I13 is opened, deionized water is added to wash the resin to neutrality, a washing liquid is discharged into the wastewater tank 6, after the washing is finished, the ionized water control valve I13 and the fifth control valve 15 are closed, and the regeneration of the small chromatographic column 4 is finished for later use.
3. Washing and eluting the large chromatographic column: after the loading of the large chromatographic column 5 is finished, an ionized water control valve II14, a second main control valve 17 and a seventh control valve 18 are opened, deionized water is added to wash the resin, the washing waste liquid is discharged from a waste liquid tank 6, after the washing is finished, the ionized water control valve II14 and the seventh control valve 18 are closed, a fourth control valve 12, the second main control valve 17 and an eighth control valve 19 are opened, the ethanol solution in the eluent tank 3 is added into the large chromatographic column 5 to elute the resin, the eluent is stored in an eluent storage tank 7, after the elution is finished, the fourth control valve 12, the second main control valve 17 and the eighth control valve 19 are closed, and the resin is ready for regeneration.
4. Regeneration of large chromatographic column: the first main control valve 10, the third control valve 11, the second main control valve 17 and the seventh control valve 18 are opened, sodium hydroxide solution in the regenerant tank 2 is added into the large chromatographic column 5 to regenerate resin, waste liquid is discharged into the waste liquid tank 6, after the regeneration process is finished, the first main control valve 10 and the third control valve 11 are closed, the ionized water control valve II14 is opened, deionized water is added to clean the resin to neutrality, cleaning solution is discharged into the waste liquid tank 6, after the water washing is finished, the ionized water control valve II14, the second main control valve 17 and the seventh control valve 18 are closed, and the resin regeneration is finished for later use.
5. And the operation of the whole column chromatography system is finished, and the next batch of production can be performed.
In the system, during the process of serially connecting fermentation filtrate to a column, impurities such as pigment, protein and the like are mainly enriched in a small chromatographic column; the micafungin mother nucleus FR179642 is mainly enriched in a large chromatographic column, after the loading is finished, the small chromatographic column contains few products, and is directly added with a regenerant for regeneration and water washing for repeated use, and the large chromatographic column is eluted by the water washing and then added with an eluent to obtain the high-purity eluent with few pigments. After the elution of the large chromatographic column is finished, adding a regenerant for regeneration and washing with water, and then repeatedly using; the transmittance (430 nm) of the eluent detection solution prepared by the system is 90.3%, the transmittance of the contrast single-column eluent is 22.3%, and the pigment of the eluent is greatly reduced, so that the subsequent purification production process is facilitated.
The foregoing description of the preferred embodiments of the utility model is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the utility model.
Claims (5)
1. A micafungin mother core FR179642 column chromatography system, characterized in that:
comprises a charging tank, a regenerant tank, an eluent tank, a small chromatographic column, a large chromatographic column, a waste liquid tank and an eluent storage tank;
the inlet of the small chromatographic column is respectively connected with the outlets of the feeding tank and the regenerant tank through a pipeline, the inlet of the small chromatographic column is also connected with a deionized water pipe I, and the outlet of the small chromatographic column is respectively connected with the inlet of the waste liquid tank and the inlet of the large chromatographic column through a pipeline;
the inlet of the large chromatographic column is respectively connected with the outlets of the charging tank, the regenerant tank and the eluent tank through pipelines, the inlet of the large chromatographic column is also connected with a deionized water pipe II, and the outlet of the large chromatographic column is respectively connected with the inlets of the waste liquid tank and the eluent storage tank through pipelines;
and the ion water pipe I, the deionized water pipe II and each pipeline are connected with a control valve.
2. A micafungin mother core FR179642 column chromatography system according to claim 1, wherein: the volume ratio of the small chromatographic column to the large chromatographic column is 1:4-1:5.
3. A micafungin mother core FR179642 column chromatography system according to claim 1, wherein: the control valve is an automatic control valve.
4. A micafungin mother core FR179642 column chromatography system according to claim 1, wherein: the feeding tank is used for containing fermentation filtrate; the regenerant tank is used for containing regenerant; the eluent tank is used for containing eluent.
5. A micafungin mother core FR179642 column chromatography system according to any one of claims 1 to 4, wherein:
the feeding tank is connected with an inlet of the small chromatographic column through a first discharging pipe, and a first control valve is connected to the first discharging pipe;
the outlet of the regenerant tank is connected with a first discharging main pipe, the first discharging main pipe is connected with a first main control valve, the first discharging main pipe is respectively connected with the inlet of the small chromatographic column and the inlet of the large chromatographic column through a second discharging pipe and a third discharging pipe, the second discharging pipe is connected with a second control valve, and the third discharging pipe is connected with a third control valve;
the outlet of the eluent tank is connected with the inlet of the large chromatographic column through a fourth discharging pipe, and a fourth control valve is connected to the fourth discharging pipe;
the ion water pipe I is connected with an ion water control valve I, and the ion water pipe I is connected with an ion water control valve II;
the outlet of the small chromatographic column is connected with the inlet of the waste liquid tank through a fifth discharge pipe, a fifth control valve is connected to the fifth discharge pipe, the outlet of the small chromatographic column is connected with the inlet of the large chromatographic column through a sixth discharge pipe, and a sixth control valve is connected to the sixth discharge pipe;
the outlet second discharging main pipe of the large chromatographic column is connected with a second main control valve, the second discharging main pipe is connected with the inlet of the waste liquid tank and the inlet of the eluent storage tank through a seventh discharging pipe and an eighth discharging pipe, the seventh discharging pipe is connected with a seventh control valve, and the eighth discharging pipe is connected with an eighth control valve.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202320600445.8U CN219539494U (en) | 2023-03-23 | 2023-03-23 | Micafungin mother nucleus FR179642 column chromatography system |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202320600445.8U CN219539494U (en) | 2023-03-23 | 2023-03-23 | Micafungin mother nucleus FR179642 column chromatography system |
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| Publication Number | Publication Date |
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| CN219539494U true CN219539494U (en) | 2023-08-18 |
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| CN202320600445.8U Active CN219539494U (en) | 2023-03-23 | 2023-03-23 | Micafungin mother nucleus FR179642 column chromatography system |
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- 2023-03-23 CN CN202320600445.8U patent/CN219539494U/en active Active
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