CN112679560A - Kasugamycin crystallization process - Google Patents
Kasugamycin crystallization process Download PDFInfo
- Publication number
- CN112679560A CN112679560A CN202110123577.1A CN202110123577A CN112679560A CN 112679560 A CN112679560 A CN 112679560A CN 202110123577 A CN202110123577 A CN 202110123577A CN 112679560 A CN112679560 A CN 112679560A
- Authority
- CN
- China
- Prior art keywords
- kasugamycin
- filtrate
- temperature
- controlled
- crystallization
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a kasugamycin crystallization process, which comprises the following steps: and adsorbing the fermentation filtrate containing kasugamycin to saturation by using cation exchange resin at the pH value of 3.0-5.0, concentrating by using a nanofiltration membrane, further decoloring by using activated carbon fibers, concentrating the filtrate in vacuum, introducing the concentrated filtrate into a crystallization reaction kettle, cooling, precipitating crystals, and finally separating to obtain the high-purity kasugamycin. The method has the advantages of high operation degree, simple process, low production cost, small environmental pollution and great popularization, and improves the equipment utilization rate and the product yield.
Description
Technical Field
The invention belongs to the field of extraction of agricultural antibiotics, and particularly relates to a kasugamycin crystallization process.
Background
Kasugamycin as an agricultural bactericide has the outstanding advantages of high efficiency, low toxicity, strong systemic property and the like, and is widely applied to diseases of rice, melons and fruits and the like. At present, the core steps of the kasugamycin purification process mainly adopt resin separation, the impurity content of a product is high, and the stability of the product is poor.
The Chinese patent application with the application patent number of 201910875502.1 discloses a preparation method of high-purity kasugamycin, which comprises the steps of ceramic membrane separation, resin separation, nanofiltration concentration, activated carbon adsorption decoloration, cooling crystallization and crystal separation in sequence to obtain the high-purity kasugamycin, and the product has stable quality and high yield.
Although the technical scheme obtains the kasugamycin with higher purity and has overhigh production cost, a large amount of industrial solid wastes are generated by adopting activated carbon for decolorization, the decolorization time is too long, the activated carbon is difficult to separate from the stock solution, crystals are separated out by vacuum evaporation, the control point is difficult to control, the crystal property is unstable, the stability of subsequent crystals is influenced, the control period of high and low temperature is too long, the stirring is opened, secondary nucleation is easily caused, the particle size distribution of the crystals is uneven, the accumulation degree is low, the mobility is poor, and the separation of subsequent products is not facilitated. The method adopts the activated carbon fiber to replace the activated carbon, reduces the cost of the decoloring process, reduces the solid waste amount, improves the product yield, shortens the decoloring time, recovers the solvent from the filtrate by decompression and concentrates the filtrate in vacuum, improves the product quality, strictly controls the cooling time and the stirring speed, accelerates the product crystallization speed, stabilizes the crystal quality, can prepare the product with good integrity, uniform granularity and high purity, can improve the yield, and is suitable for industrial production.
Disclosure of Invention
In order to solve the technical problems in the prior art, the invention provides a kasugamycin crystallization process, which has the advantages of high operation degree, small environmental pollution, simple process, low production cost, stable and uniform product properties and great popularization, and improves the equipment utilization rate and the product yield.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows: a kasugamycin crystallization process comprises the following steps: adsorbing the fermentation filtrate containing kasugamycin to saturation by using cation exchange resin at the pH value of 3.0-5.0, concentrating by using a nanofiltration membrane, further decoloring by using activated carbon fibers, concentrating the filtrate in vacuum, introducing the concentrated filtrate into a crystallization reaction kettle, cooling, precipitating crystals, and finally separating to obtain the high-purity kasugamycin.
More specifically, the process comprises the following steps:
1) ion exchange adsorption: adsorbing the fermentation filtrate containing kasugamycin to saturation by using cation exchange resin at the pH of 3.0-5.0, controlling the adsorption flow rate to be 0.3-1.5 BV/h, washing by using saline-free water with the resin content not less than 1.5 times of the resin content after the adsorption is saturated, starting elution, and collecting eluent;
2) nanofiltration and concentration: controlling the titer of the concentrated solution to 55000-65000 units according to the properties of the eluent, and stopping concentration;
3) active carbon fiber decoloration: decolorizing nanofiltration concentrated solution containing kasugamycin by adopting activated carbon fiber, and collecting filtrate with transmittance of over 60%;
4) and (3) vacuum concentration: concentrating the filtrate obtained after decolorization by a vacuum film concentrator until obvious crystals appear, adding part of dilute solution, and then introducing into a crystallization kettle;
5) cooling and crystallizing: slowly cooling, controlling the crystallization temperature to 45 +/-0.05 ℃ by using circulating water, continuously stirring, growing crystals for 1-2 hours after nucleation, rapidly cooling to 5-10 ℃, growing crystals for 1-2 hours, and filtering and drying to obtain the finished product of kasugamycin.
In a preferred embodiment of the invention, in step (1), the unit of kasugamycin fermentation filtrate is 4500 or more, and the eluent is 2.5-4.0 wt% of ammonium chloride.
In a preferred embodiment of the invention, nanofiltration concentration is performed in the step (2), the membrane pressure is controlled to be 0.5MPa to 1.5MPa, pure water is supplemented, the unit of the concentrated solution is controlled to be 55000 to 70000 units, water with the volume of 0.5 to 1.5BV is supplemented in the middle for dialysis, the conductivity of the feed liquid is controlled to be relatively stable, and the temperature is stabilized to be 30 ℃ to 40 ℃.
In a preferred embodiment of the invention, in the step (3), the nanofiltration concentrated solution is decolorized by 3-5 grade activated carbon fibers, the decolorization temperature is controlled to be 30-45 ℃, the treatment time is 1-2 hours, and the feed solution passes through a fine filter and OD26010-20, and the light transmittance is more than 60%.
In a preferred embodiment of the invention, in the step (3), the activated carbon fibers are regenerated by steam desorption and continuously used, and the activated carbon fibers can be repeatedly used for 120-150 batches.
In a preferred embodiment of the present invention, in the step (4), the filtrate after decolorization is concentrated under reduced pressure to 30 to 40 ten thousand units at 50 to 70 ℃ under-0.06 to 0.095 MPa.
In a preferred embodiment of the invention, in the step (5), the temperature is slowly reduced, the rate of temperature reduction is controlled to be 0.15-0.25 ℃/min, the mixture is stirred at the speed of 90-120 rpm, the temperature is reduced to 45 +/-0.05 ℃ for 1-2 h, the temperature is rapidly reduced after crystal growth is carried out for 1-2 h, the rate of temperature reduction is controlled to be 0.3-0.5 ℃/min, the mixture is rapidly cooled to be 5-10 ℃, and a kasugamycin finished product is obtained after filtration and drying after crystallization is completed.
Compared with the prior art, the invention has the beneficial effects that: the invention provides a method for improving purity of kasugamycin, which adopts activated carbon fiber for decolorization, reduces cost of a decolorization process, reduces solid waste amount, improves product yield, shortens decolorization time, recovers a solvent from filtrate through reduced pressure, concentrates the filtrate through a vacuum film, improves product quality, strictly controls the temperature reduction time, controls stirring speed, accelerates product crystallization speed, stabilizes crystal quality, can prepare crystals with good integrity, uniform granularity and high purity, can improve yield, and is suitable for industrial production. The method has the advantages of simple process, strong operability, small environmental pollution and great popularization significance.
Drawings
The following is further described with reference to the accompanying drawings:
FIG. 1 is a process flow diagram of the present invention.
Detailed Description
The present invention will be further described with reference to the following examples, but the present invention is not limited to the following examples. Unless otherwise defined, all terms of art used hereinafter have the same meaning as commonly understood by one of ordinary skill in the art. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention.
The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.
Example 1
1) And (2) statically adsorbing the kasugamycin-containing fermentation filtrate at the pH value of 3.0-5.0 by using cation exchange resin at the stirring speed of 50rpm until the fermentation filtrate is saturated, washing the fermentation filtrate with brine which is not less than 2 times of the resin amount to remove polar substances, and eluting the kasugamycin at the flow rate which is 3 times of the resin amount by using ammonium chloride which is 2.5wt% of 4 times of the resin amount.
2) Controlling the membrane pressure to be 0.5-1.5 Mpa, supplementing pure water, and controlling the concentration unit to be 58000 +/-300 units.
3) Decolorizing with activated carbon fiber at 30 deg.c for 1-2 hr, filtering with fine liquid filter to obtain decolorized material with yield up to 99.2%, filtrate with light transmittance of 65 +/-2% and OD260Between 10 and 20.
4) And (3) introducing the decolorized filtrate into a vacuum film concentrator through a pipeline, decompressing, controlling the pressure to be-0.06 Mpa and the temperature to be 50 +/-0.5 ℃, decompressing, recovering the solvent, and concentrating the filtrate to 30 ten thousand units.
5) The temperature is slowly reduced, the temperature reduction rate is controlled to be 0.25 ℃/min, the stirring speed is 90rpm, the temperature is reduced to 45 +/-0.05 ℃ after 1 hour, the temperature is rapidly reduced after 2 hours of crystal growth, the temperature reduction rate is 0.5 ℃/min, the temperature is rapidly reduced to 5-10 ℃, the feed liquid is finished after a large amount of needle crystals appear, and the kasugamycin finished product is obtained after filtration and drying. The average yield of the product is 85% and the purity of the product is 90% through determination.
Example 2
1) And (3) dynamically adsorbing the kasugamycin-containing fermentation filtrate at the pH value of 3.0-5.0 by using cation exchange resin at the rate of 1.05 BV/h until the fermentation filtrate is saturated, washing polar substances by using water with the amount not less than 2 times that of the resin, and then eluting the kasugamycin at the rate of 1.5BV/h by using ammonium chloride with the amount not less than 3 times that of the resin and 3.5 percent.
2) Controlling the membrane pressure to be 0.5-1.5 Mpa, supplementing pure water, and controlling the concentration unit to be 60000 +/-300 units.
3) Decolorizing with activated carbon fiber at 35 deg.C for 2 hr, filtering with liquid fine filter to obtain filtrate with decolorization yield of 99.2%, light transmittance of 70% +/-2%, and OD260Between 10 and 20.
4) And (3) after decolorization, introducing the filtrate into a vacuum film concentrator through a pipeline, decompressing, controlling the pressure to be 0.075Mpa at 60 ℃, decompressing, recovering the solvent, and concentrating the filtrate to 40 ten thousand units.
5) Slowly cooling, controlling the cooling rate to be 0.25 ℃/min, stirring at 90rpm, cooling to 45 +/-0.05 ℃ after 1h, growing the crystals for 2 hours, rapidly cooling, controlling the cooling rate to be 0.5 ℃/min, rapidly cooling to 10 ℃, completing the formation of a large amount of needle crystals in the feed liquid, and filtering and drying to obtain the kasugamycin finished product. The average yield of the product is determined to be 90 percent, and the purity of the product is determined to be 92 percent.
Example 3
1) And (3) dynamically adsorbing the kasugamycin-containing fermentation filtrate at the pH value of 3.0-5.0 by using cation exchange resin at the rate of 1.5BV/h until the fermentation filtrate is saturated, washing polar substances by using water with the amount not less than 2 times that of the resin, and then eluting the kasugamycin at the rate of 1.5BV/h by using ammonium chloride with the amount not less than 3 times that of the resin and 3.5 percent.
2) Controlling the membrane pressure to be 0.5-1.5 Mpa, supplementing pure water, and controlling the concentration unit to be 60000 +/-300 units.
3) Decolorizing with activated carbon fiber at 37 deg.C for 1 hr, filtering with liquid fine filter to obtain filtrate with decolorization yield of 99.8%, light transmittance of 60 + -5 and OD260Between 10 and 20.
4) And (3) introducing the decolorized filtrate into a vacuum film concentrator through a pipeline, decompressing, controlling the pressure to be 0.095Mpa at 70 ℃, decompressing, recovering the solvent, and concentrating the filtrate to 40 ten thousand units.
5) The temperature is slowly reduced, the temperature reduction rate is controlled to be 0.25 ℃/min, the stirring speed is 120rpm, the temperature is reduced to 45 +/-0.05 ℃ after 1.5 hours, the temperature is rapidly reduced after 2 hours of crystal growth, the temperature reduction rate is 0.5 ℃/min, the temperature is rapidly reduced to 5 ℃, the feed liquid is completely crystallized in a large number of needle-shaped crystals, the kasugamycin finished product is obtained after filtration and drying, the average yield of the product is determined to be 90%, and the purity of the product is determined to be 85%.
Example 4
1) And (3) dynamically adsorbing the kasugamycin-containing fermentation filtrate at the pH value of 3.0-5.0 by using cation exchange resin at the rate of 1.05 BV/h until the fermentation filtrate is saturated, washing polar substances by using water with the amount not less than 2 times that of the resin, and then eluting the kasugamycin at the rate of 1.5BV/h by using ammonium chloride with the amount not less than 3 times that of the resin and 3.5 percent.
2) Controlling the membrane pressure to be 0.5-1.5 Mpa, adding pure water, controlling the concentration unit to be 65000 +/-300 units, and controlling the concentration yield to be 90-95%.
3) Decolorizing with activated carbon fiber at 40 deg.C for 2 hr, filtering with liquid fine filter to obtain filtrate with decolorization yield of 99.5% and transmittance of 70% or more and OD260Between 10 and 20.
4) And (3) feeding the decolorized filtrate into a vacuum film concentrator through a pipeline, decompressing, controlling the pressure to be 0.06MPa below zero and the temperature to be 50 ℃, decompressing, recovering the solvent, and concentrating the filtrate to 40 ten thousand units.
5) Slowly cooling, controlling the cooling rate to be 0.15 ℃/min, stirring at 120rpm, cooling to about 45 ℃ after 0.5 hour, growing the crystals for 2 hours, rapidly cooling, controlling the cooling rate to be 0.3 ℃/min, rapidly cooling, cooling to 10 ℃ after 2 hours, finishing the feed liquid after a large amount of needle crystals appear, and filtering and drying to obtain the kasugamycin finished product. The average yield of the product is 92% and the purity of the product is 90% through determination.
Example 5
1) And (3) dynamically adsorbing the fermentation filtrate containing kasugamycin to saturation at the pH value of 3.0-5.0 by using cation exchange resin at the rate of 1.05 BV/h, washing polar substances by using water with the amount not less than 2 times of the resin, and then eluting the kasugamycin at the rate of 1.5BV/h by using ammonium chloride with the amount 3 times of the resin and 3.5 percent of the resin.
2) Controlling the membrane pressure to be 0.5-1.5 MPa, supplementing pure water, and controlling the concentration unit to be 58000 +/-300 units.
3) Decolorizing with activated carbon fiber at 40 deg.c for 1-2 hr, filtering with fine liquid filter to obtain filtrate with decolorizing yield up to 99.0%, light transmittance over 60% and OD260Between 10 and 20.
4) And (3) introducing the decolorized filtrate into a vacuum film concentrator through a pipeline, decompressing, controlling the pressure to be 0.095Mpa at 70 ℃, decompressing, recovering the solvent, and concentrating the filtrate to 40 ten thousand units.
5) Slowly cooling, controlling the cooling rate to be 0.15 ℃/min, stirring at 100rpm, cooling 2xi to be about 45 ℃, growing crystals for 1 hour, rapidly cooling, controlling the cooling rate to be 0.5 ℃/min, rapidly cooling to be 5 ℃, finishing the feed liquid after a large amount of needle crystals appear, and filtering and drying to obtain the kasugamycin finished product. The average yield of the product is 85% and the purity of the product is 90% through determination.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art will understand that various changes, modifications and substitutions can be made without departing from the spirit and scope of the invention as defined by the appended claims. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (8)
1. A kasugamycin crystallization process is characterized by comprising the following steps: adsorbing the fermentation filtrate containing kasugamycin to saturation by using cation exchange resin at the pH value of 3.0-5.0, concentrating by using a nanofiltration membrane, further decoloring by using activated carbon fibers, concentrating the filtrate in vacuum, introducing the concentrated filtrate into a crystallization reaction kettle, cooling, precipitating crystals, and finally separating to obtain the high-purity kasugamycin.
2. The process according to claim 1, characterized in that it comprises the following steps:
1) ion exchange adsorption: adsorbing the fermentation filtrate containing kasugamycin to saturation by using cation exchange resin at the pH of 3.0-5.0, controlling the adsorption flow rate to be 0.3-1.5 BV/h, washing by using saline-free water with the resin content not less than 1.5 times of the resin content after the adsorption is saturated, starting elution, and collecting eluent;
2) nanofiltration and concentration: controlling the titer of the concentrated solution to 55000-65000 units according to the properties of the eluent, and stopping concentration;
3) active carbon fiber decoloration: decolorizing nanofiltration concentrated solution containing kasugamycin by adopting activated carbon fiber, and collecting filtrate with transmittance of over 60%;
4) and (3) vacuum concentration: concentrating the filtrate obtained after decolorization by a vacuum film concentrator until obvious crystals appear, adding part of dilute solution, and then introducing into a crystallization kettle;
5) cooling and crystallizing: slowly cooling, controlling the crystallization temperature to 45 +/-0.05 ℃ by using circulating water, continuously stirring, growing crystals for 1-2 hours after nucleation, rapidly cooling to 5-10 ℃, growing crystals for 1-2 hours, and filtering and drying to obtain the finished product of kasugamycin.
3. The process as claimed in claim 2, wherein in step (1), the kasugamycin fermentation filtrate unit is above 4500, and the eluent is 2.5-4.0 wt% ammonium chloride.
4. The process according to claim 2, wherein in the step (2), nanofiltration concentration is performed, the membrane pressure is controlled to be 0.5MPa to 1.5MPa, pure water is supplemented, the unit of the concentrated solution is controlled to be 55000 to 70000 units, water with the volume of 0.5 to 1.5BV is supplemented in the middle for dialysis, the conductivity of the feed liquid is controlled to be relatively stable, and the temperature is controlled to be stable to be 30 ℃ to 40 ℃.
5. The process according to claim 2, wherein in the step (3), the nanofiltration concentrate is decolorized by 3-5 grade activated carbon fibers, the decolorization temperature is controlled to be 30-45 ℃, the treatment time is 1-2 hours, and the feed liquid passes through a fine filter and OD26010-20, and the light transmittance is more than 60%.
6. The process according to claim 2, wherein in the step (3), the activated carbon fibers are regenerated by steam desorption and are continuously used for 120-150 batches.
7. The process as claimed in claim 2, wherein in the step (4), the decolorized filtrate is concentrated under reduced pressure to 30-40 ten thousand units at-0.06-0.095 MPa and 50-70 ℃.
8. The process according to claim 2, wherein in the step (5), the temperature is slowly reduced, the temperature reduction rate is controlled to be 0.15-0.25 ℃/min, the stirring is carried out at the speed of 90-120 rpm, the temperature is reduced to 45 +/-0.05 ℃ for 1-2 h, the temperature is rapidly reduced after the crystal is grown for 1-2 h, the temperature reduction rate is controlled to be 0.3-0.5 ℃/min, the temperature is rapidly reduced to be 5-10 ℃, and the finished kasugamycin product is obtained after the crystallization is finished and the filtration and the drying.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110123577.1A CN112679560A (en) | 2021-01-29 | 2021-01-29 | Kasugamycin crystallization process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110123577.1A CN112679560A (en) | 2021-01-29 | 2021-01-29 | Kasugamycin crystallization process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112679560A true CN112679560A (en) | 2021-04-20 |
Family
ID=75459464
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110123577.1A Pending CN112679560A (en) | 2021-01-29 | 2021-01-29 | Kasugamycin crystallization process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112679560A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114230622A (en) * | 2021-11-12 | 2022-03-25 | 陕西麦可罗生物科技有限公司 | Method for decoloring kasugamycin concentrated solution |
| CN116715709A (en) * | 2023-08-03 | 2023-09-08 | 中国远大集团有限责任公司 | Compound hydrochloride crystal form and application thereof |
-
2021
- 2021-01-29 CN CN202110123577.1A patent/CN112679560A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114230622A (en) * | 2021-11-12 | 2022-03-25 | 陕西麦可罗生物科技有限公司 | Method for decoloring kasugamycin concentrated solution |
| CN116715709A (en) * | 2023-08-03 | 2023-09-08 | 中国远大集团有限责任公司 | Compound hydrochloride crystal form and application thereof |
| CN116715709B (en) * | 2023-08-03 | 2023-10-27 | 中国远大集团有限责任公司 | Compound hydrochloride crystal form and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102363594B (en) | Method for separating and purifying succinic acid from fermentation broth | |
| CN112679560A (en) | Kasugamycin crystallization process | |
| CN113004320B (en) | Method for reducing consumption of desorbent in production of inositol | |
| WO2023124395A1 (en) | System and method for co-producing xylitol and caramel color by using xylose mother liquor | |
| CN114933288A (en) | High-purity monopotassium phosphate and preparation method thereof | |
| CN113004347B (en) | Method for separating and purifying 2' -fucosyllactose | |
| CN110452275B (en) | Preparation method of high-purity kasugamycin | |
| CN101100437A (en) | Method for preparing high-purity beta-alanine | |
| CN114436816B (en) | Method for efficiently extracting shikimic acid by ion exchange technology | |
| KR100864673B1 (en) | Method of recovering L-Threonine from L-Threonine fermentation broth using a nonsolvent | |
| CN113135965A (en) | System and method for producing crystalline xylose by using xylose mother liquor | |
| CN110407388B (en) | Recycling treatment method of glutamic acid concentrated isoelectric extraction waste liquid | |
| CN111115936A (en) | Membrane method treatment process of gallic acid crystallization mother liquor | |
| CN215049793U (en) | System for utilize xylose mother liquor production crystallization xylose | |
| CN115626882B (en) | Purification method of creatine monohydrate | |
| CN113185397B (en) | Method for recovering malic acid from fermentation broth | |
| CN114105849B (en) | Extraction method of L-hydroxyproline | |
| US4588818A (en) | Method for recovery of optically active tryptophane | |
| CN216614473U (en) | System for utilize xylose mother liquor coproduction xylitol and caramel pigment | |
| CN117800523A (en) | Preparation method of byproduct industrial salt in riboflavin production process | |
| CN115088829B (en) | Production process for improving chromaticity of monosodium glutamate product | |
| CN114213241B (en) | Method for extracting shikimic acid from shikimic acid fermentation liquor | |
| CN118084655A (en) | Method for purifying L-malic acid from fermentation broth | |
| CN117902974A (en) | Method for recovering succinic acid and malic acid from succinic acid mother liquor | |
| CN117736122A (en) | Separation and purification method of arginine fermentation liquor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |