CN110452275A - A kind of preparation method of high-purity kasugarnycin - Google Patents
A kind of preparation method of high-purity kasugarnycin Download PDFInfo
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- CN110452275A CN110452275A CN201910875502.1A CN201910875502A CN110452275A CN 110452275 A CN110452275 A CN 110452275A CN 201910875502 A CN201910875502 A CN 201910875502A CN 110452275 A CN110452275 A CN 110452275A
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- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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Abstract
The step of the present invention relates to a kind of preparation methods of high-purity kasugarnycin, successively separate and dry by ceramic clear liquid, resin adsorption separation, nanofiltration concentration, active carbon processing, vacuum evaporation, decrease temperature crystalline, crystal.The present invention is on the basis of existing production technology, it is once decolourized using traditional active carbon to concentrate, solubility is gradually decreased using the concentration of double-effect evaporation low boiling point and controlling temperature, the method that crystallization is precipitated, design the preparation method and production technology of the separation of high-purity kasugarnycin, the purity of kasugarnycin original powder is increased to 90% or more, 85% or more yield, the quality index such as the stable crystal form of raw medicine and purity further increase, the quality control cost of downstream industry chain is greatly reduced, is conducive to enhance pharmaceutical manufacturer's sustainable development.
Description
Technical field
The invention belongs to farm antibiotics extractive technique fields, and in particular to a kind of preparation side of high-purity kasugarnycin
Method.
Background technique
Kasugarnycin is as a kind of green, less toxic, low-residual farm antibiotics class fungicide, before having good market
Scape, current main production process core procedure are resin method separation, and index of central control is relatively fewer, and stable product quality is not
Height produces bigger effect the product quality of the production of the raw medicine in downstream and preparation, aqua, composite pesticide.
Application No. is 201810817180.0 Chinese patent applications to disclose a kind of method for improving kasugarnycin content,
The kasugarnycin raw medicine pesticide is obtained after acidified, ceramic membrane filter, ion exchange resin and spray drying, by these
The resulting kasugarnycin raw medicine mass percent containing kasugarnycin of isolation and purification technique is 60-70%, each isolation and purification workshop section
It is all made of ultrasonication, ultrasonic frequency 10-35KHz, ultrasonic power 1.0-3.0Kw.The program realizes kasugarnycin
Drug effect improve, further decrease production cost, promote the product quality of the kasugarnycin, obtained high-content kasugarnycin is former
Medicine drug effect is efficient, safe and environment-friendly and be conducive to germ resistance management.
Application No. is the Chinese patent applications of 201710965305.X to disclose a kind of purification process of kasugarnycin, described
Method include the following steps: 1) containing kasugarnycin clear liquid preparation.2) chromatography media pre-processes.3) loading.4) it elutes.5)
Condensing crystallizing.Kasugarnycin is purified using the present invention, there is purity is high, high income, environmentally protective beneficial effect.
The index of central control of above-mentioned technical proposal is relatively fewer, and stable product quality is not high, and obtained purity is not also high.Cause
This, is badly in need of developing a kind of more optimal technique in this field, to meet the requirement of product stability of crystal form and high-purity, together
Shi Heli controls production cost.The present invention carries out single treatment to concentrate using active carbon, and vacuum evaporation passes through high and low temperature
It controls solubility and crystal is precipitated, can effectively improve the quality of material, stablize the matter such as stable crystal form and the purity raising of raw medicine
Figureofmerit greatly reduces the quality control cost of downstream industry chain.Product quality further increases simultaneously, increases production enterprise
The productivity effect of industry and domestic and international competitiveness are conducive to enhance pharmaceutical manufacturer's sustainable development.
Summary of the invention
In order to solve the above-mentioned technical problem, the object of the present invention is to provide a kind of preparation method of high-purity kasugarnycin,
Successively by ceramic clear liquid, resin adsorption separation, nanofiltration concentration, active carbon processing, vacuum evaporation, decrease temperature crystalline, crystal
The step of separation and drying.The present invention carries out concentrate on the basis of existing production technology, using traditional active carbon primary
Decoloration gradually decreases solubility using the concentration of double-effect evaporation low boiling point and controlling temperature, and the method that crystallization is precipitated designs high-purity
The preparation method and production technology of kasugarnycin separation, the technique can be effectively reduced production waste amount and ammonia nitrogen input amount.
More specifically, the technical solution used in the present invention is as follows:
A kind of preparation method of high-purity kasugarnycin includes its following processing step:
1) ceramic clear liquid resin adsorption separation: absorption feed flow rate is that 0.3-0.6BV/h is first carried out with pure water after saturation absorption
Backwash ion-exchange column, then starts to elute, and collects eluent；
2) nanofiltration is concentrated: membrane pressure is controlled in 0.5-1.0Mpa, and pure water is added in centre, is down to 1/10 or so to volume, nanofiltration concentration
Terminate；
3) active carbon is handled: being stopped stirring than qualitative activity charcoal, stir process 2-3h is added by ceramic supernatant volume, is stood
0.5-1h, feed liquid are squeezed into sheet frame and are filtered, and filtrate, filtrate light transmittance > 55% are collected；
4) double-effect evaporation: after sheet frame filtrate enters evaporator, temperature is controlled at 80-95 DEG C, after there is obvious nucleus, prepares
Material；
5) decrease temperature crystalline: concentrate is beaten to crystallizing tank, recirculated water slow cooling, and midfeather opens stirring, is cooled to 5-10
DEG C, educate brilliant 2-3h；
6) crystal separates: being filtered using geosyncline or centrifuge carries out crystallized stock separation；
7) dry: crystal is dried, and into lower road preparation process, or after sieving, original powder is packed.
In step (1), eluted with 3.5% sodium chloride.
In step (2), nanofiltration concentration process, concentrate unit reaches 60,000-8 ten thousand units.
In step (2), nanofiltration concentration process adds 0.5-1BV water and dialyses, and control electric conductivity value is relatively stable.
In step (3), active carbon treatment process, temperature is controlled at 35-65 DEG C.
In step (3), according to feed liquid temperature difference, by volume be added 0.3-0.5% active carbon, OD280 10-20,
Light transmittance is greater than 55%.
In step (4), it is concentrated by evaporation to more than 250,000 unit of theoretical concentration, highest theoretical concentration to ten thousand unit of 40-45.
In step (5), normal temperature circulation water slow cooling is first used, after 6h-8h is down to room temperature, opens chilled water, fast prompt drop
Temperature is to 5-10 DEG C.
In step (6), the later period is separated in geosyncline or centrifuge, carries out washing crystalline substance with a small amount of 95% ethyl alcohol, until efflux is colourless
It is transparent.
Compared with prior art, the invention has the benefit that
1) present invention provides the preparation method and production technology of a kind of high-purity kasugarnycin, on the basis of original production process,
It is once decolourized, is gradually decreased using the concentration of double-effect evaporation low boiling point and controlling temperature molten to concentrate using traditional active carbon
Xie Du, the method that crystallization is precipitated design the preparation method and production technology of the separation of high-purity kasugarnycin.Technique of the invention
Stablize easy to operate, production investment is less, and intermediate mass index controllability is higher, can effectively improve every technique of intermediate material
Quality index, the active compound content of production are increased to 90% or more by the 65-70% of original process, and yield is 85% or more, raw medicine
The quality index such as stable crystal form and purity raising further increase.
(2) the more uniform stabilization of kasugarnycin raw medicine crystal form that the present invention produces, pulvis mobility significantly improve, have
Conducive to the raw medicine production in downstream, the stable product quality of preparation, aqua, composite pesticide, downstream industry chain can be reduced
Quality control cost, while product quality further increases, and increases the productivity effect and domestic and international competitiveness of manufacturing enterprise, has
Conducive to enhancing pharmaceutical manufacturer's sustainable development.
Detailed description of the invention
It is described further with reference to the accompanying drawing:
Fig. 1 is high-purity kasugarnycin preparation technology flow chart.
Specific embodiment
It is explained below substantive distinguishing features of the present invention with example, it is understood that, example is not intended to limit for illustrating
The embodiment of the invention, the scope of the present invention are determined with core content according to claims.
Kasugarnycin ceramics clear liquid source in following embodiments:
The acquisition of kasugarnycin ceramics clear liquid: three grade fermemtation generates kasugarnycin fermentation liquid, and every batch of content is 8-14g/L, fermentation
After liquid acidification, it is separated by solid-liquid separation into microfiltration membranes, kasugarnycin ceramics clear liquid can be obtained.
High-purity kasugarnycin preparation process flow is as shown in Figure 1.
Embodiment 1
1) ceramic clear liquid resin adsorption separation: single-column is used, feed flow rate is set as 0.6BV/h early period, and the later period is set as
0.3BV/h first carries out backwash ion-exchange column with pure water, then starts to elute, eluted with 3.5% sodium chloride after saturation absorption,
Eluent is collected, elutes material mean titre between 1.5 ten thousand -2.5 ten thousand units, elutes yield between 90-93%.
2) nanofiltration is concentrated: membrane pressure control adds pure water among 0.5-1.0Mpa, nanofiltration concentration process, adds 0.5-1BV
Water is dialysed, and is down to 1/10 or so to volume, and concentrate unit reaches 60,000-8 ten thousand units, and nanofiltration concentrate conductance is stablized,
Nanofiltration concentration terminates, and condenses liquid yield between 93-95%.
3) active carbon is handled: being controlled at 60-65 DEG C, at stirring by ceramic supernatant volume than 0.3% active carbon, temperature is added
2-3h is managed, stands 0.5-1h after stopping stirring, feed liquid squeezes into plate-frame filtering, collects filtrate, between 10 and 20, filtrate is saturating by OD280
Light rate > 55%, the yield that decolourizes is in 98-99%.
4) double-effect evaporation: after sheet frame filtrate enters evaporator, temperature is controlled at 80-95 DEG C, is concentrated into theoretical concentration 250,000
More than unit, after there is obvious nucleus, prepare discharging, highest theoretical concentration to ten thousand unit of 40-45, evaporation yield 99-100% steams
Send out yield 99-100%.
5) decrease temperature crystalline: concentrate is beaten to crystallizing tank, first uses normal temperature circulation water slow cooling, and midfeather is opened
Stirring after 6-8h is down to room temperature, opens chilled water, and fast cooling educates brilliant 2-3h to 5-10 DEG C, and crystal is at single-size in material
Powdery or elongated piece.
6) crystal separates: being filtered using geosyncline or centrifuge carries out crystallized stock separation, separate the later period in geosyncline or centrifugation
It in machine, carries out washing crystalline substance with a small amount of 95% ethyl alcohol, until efflux is colorless and transparent, crystalline mother solution content is in ten thousand unit of 0.6-0.8, mother liquor
The rate of recovery is between 3-4%, and crystalline deposit rate is between 96-97%.
7) dry: crystal is dried, and into lower road preparation process, or after sieving, original powder is packed.Sample original powder is white
Or pure white, have glossy, granular size is uniform, and mobility is obvious, it is micro- it is lower be systematicness acicular crystal.First drying material is total
Yield is between 80-83%, and original powder content is between 88-92%.
Embodiment 2
1) ceramic clear liquid resin adsorption separation: 2-3 serial column absroption is used, feed flow rate is set as 0.6BV/h early period, and the later period sets
0.4BV/h is set to first to carry out backwash ion-exchange column after saturation absorption with pure water, then start to elute, carried out with 3.5% sodium chloride
Eluent is collected in elution, elutes material mean titre between 2.5 ten thousand -3 ten thousand units, elutes yield between 95-97%.
2) nanofiltration is concentrated: membrane pressure control adds pure water among 0.5-1.0Mpa, nanofiltration concentration process, adds 0.5-1BV
Water is dialysed, and is down to 1/10 or so to volume, and concentrate unit reaches 60,000-8 ten thousand units, and nanofiltration concentrate conductance is stablized,
Nanofiltration concentration terminates, and condenses liquid yield between 94-97%.
3) active carbon is handled: being controlled at 60-65 DEG C, at stirring by ceramic supernatant volume than 0.3% active carbon, temperature is added
2-3h is managed, stands 0.5-1h after stopping stirring, feed liquid squeezes into plate-frame filtering, collects filtrate, between 10 and 20, filtrate is saturating by OD280
Light rate > 55%, the yield that decolourizes is in 98-99%.
4) double-effect evaporation: after sheet frame filtrate enters evaporator, temperature is controlled at 80-95 DEG C, is concentrated into theoretical concentration 250,000
More than unit, after there is obvious nucleus, prepare discharging, highest theoretical concentration to ten thousand unit of 40-45, evaporation yield 99-100%.
5) decrease temperature crystalline: concentrate is beaten to crystallizing tank, first uses normal temperature circulation water slow cooling, and midfeather is opened
Stirring after 6h-8h is down to room temperature, opens chilled water, and fast cooling educates brilliant 2-3h, crystal is at uniform in material to 5-10 DEG C
Grain powdery or elongated piece.
6) crystal separates: being filtered using geosyncline or centrifuge carries out crystallized stock separation, separate the later period in geosyncline or centrifugation
It in machine, carries out washing crystalline substance with a small amount of 95% ethyl alcohol, until efflux is colorless and transparent, crystalline mother solution content is in ten thousand unit of 0.6-0.8, mother liquor
The rate of recovery is between 3-4%, and crystalline deposit rate is between 96-97%.
7) dry: crystal is dried, and into lower road preparation process, or after sieving, original powder is packed.Sample original powder is white
Or pure white, have glossy, granular size is uniform, and mobility is obvious, it is micro- it is lower be systematicness acicular crystal.First drying material is total
Yield is between 83-85%, and original powder content is between 90-95%.
Embodiment 3
1) ceramic clear liquid resin adsorption separation: single-column is used, feed flow rate is set as 0.6BV/h early period, and the later period is set as
0.3BV/h first carries out backwash ion-exchange column with pure water, then starts to elute, eluted with 3.5% sodium chloride after saturation absorption,
Eluent is collected, elutes material mean titre between 1.5 ten thousand -2.5 ten thousand units, elutes yield between 90-93%.
2) nanofiltration is concentrated: membrane pressure control adds pure water among 0.5-1.0Mpa, nanofiltration concentration process, adds 0.5-1BV
Water is dialysed, and is down to 1/10 or so to volume, and concentrate unit reaches 60,000-8 ten thousand units, and nanofiltration concentrate conductance is stablized,
Nanofiltration concentration terminates, and condenses liquid yield between 93-95%.
3) active carbon is handled: being controlled at 45-50 DEG C, at stirring by ceramic supernatant volume than 0.3% active carbon, temperature is added
2-3h is managed, stands 0.5-1h after stopping stirring, feed liquid squeezes into plate-frame filtering, collects filtrate, between 10 and 20, filtrate is saturating by OD280
Light rate > 55%, the yield that decolourizes is in 98-99%.
4) double-effect evaporation: after sheet frame filtrate enters evaporator, temperature is controlled at 80-95 DEG C, is concentrated into theoretical concentration 250,000
More than unit, after there is obvious nucleus, prepare discharging, highest theoretical concentration to ten thousand unit of 40-45, evaporation yield 99-100%.
5) decrease temperature crystalline: concentrate is beaten to crystallizing tank, first uses normal temperature circulation water slow cooling, and midfeather is opened
Stirring after 6h-8h is down to room temperature, opens chilled water, and fast cooling educates brilliant 2-3h to 5-10 DEG C, in material crystal at particle or
Needle-like crystal grain.
6) crystal separates: being filtered using geosyncline or centrifuge carries out crystallized stock separation, separate the later period in geosyncline or centrifugation
It in machine, carries out washing crystalline substance with a small amount of 95% ethyl alcohol, until efflux is colorless and transparent, crystalline mother solution content is in ten thousand unit of 0.6-0.8, mother liquor
The rate of recovery is between 3-4%, and crystalline deposit rate is between 96-97%.
7) dry: crystal is dried, and into lower road preparation process, or after sieving, original powder is packed.Sample original powder is white
Or pure white, have glossy, granular size is uniform, and mobility is obvious, it is micro- it is lower be systematicness acicular crystal.First drying material is total
Yield is between 80-83%, and original powder content is between 88-92%.
Embodiment 4
1) ceramic clear liquid resin adsorption separation: single-column is used, feed flow rate is set as 0.6BV/h early period, and the later period is set as
0.3BV/h first carries out backwash ion-exchange column with pure water, then starts to elute, eluted with 3.5% sodium chloride after saturation absorption,
Eluent is collected, elutes material mean titre between 1.5 ten thousand -2.5 ten thousand units, elutes yield between 90-93%.
2) nanofiltration is concentrated: membrane pressure control adds pure water among 0.5-1.0Mpa, nanofiltration concentration process, adds 0.5-1BV
Water is dialysed, and is down to 1/10 or so to volume, and concentrate unit reaches 60,000-8 ten thousand units, and nanofiltration concentrate conductance is stablized,
Nanofiltration concentration terminates, and condenses liquid yield between 93-95%.
3) active carbon is handled: being controlled than 0.5% active carbon, temperature is added at 35 DEG C by ceramic supernatant volume, stir process
3h stands 0.5-1h after stopping stirring, and feed liquid squeezes into plate-frame filtering, collects filtrate, OD280 between 10 and 20, filtrate light transmittance
> 55%, the yield that decolourizes is in 97-98%.
4) double-effect evaporation: after sheet frame filtrate enters evaporator, temperature is controlled at 80-95 DEG C, is concentrated into theoretical concentration 250,000
More than unit, after there is obvious nucleus, prepare discharging, highest theoretical concentration to ten thousand unit of 40-45, evaporation yield 99-100%.
5) decrease temperature crystalline: concentrate is beaten to crystallizing tank, first uses normal temperature circulation water slow cooling, and midfeather is opened
Stirring after 6h-8h is down to room temperature, opens chilled water, and fast cooling educates brilliant 2-3h to 5-10 DEG C, in material crystal at particle or
Needle-like crystal grain.
6) crystal separates: being filtered using geosyncline or centrifuge carries out crystallized stock separation, separate the later period in geosyncline or centrifugation
It in machine, carries out washing crystalline substance with a small amount of 95% ethyl alcohol, until efflux is colorless and transparent, crystalline mother solution content is in ten thousand unit of 0.6-0.8, mother liquor
The rate of recovery is between 3-4%, and crystalline deposit rate is between 96-97%.
7) dry: crystal is dried, and into lower road preparation process, or after sieving, original powder is packed.Sample original powder is white
Or pure white, have glossy, granular size is uniform, and mobility is obvious, it is micro- it is lower be systematicness acicular crystal.First drying material is total
Yield is between 80-83%, and original powder content is between 88-92%.
Embodiment 5
1) ceramic clear liquid resin adsorption separation: 2-3 serial column absroption is used, feed flow rate is set as 0.6BV/h early period, and the later period sets
0.4BV/h is set to first to carry out backwash ion-exchange column after saturation absorption with pure water, then start to elute, carried out with 3.5% sodium chloride
Eluent is collected in elution, elutes material mean titre between 2.5 ten thousand -3 ten thousand units, elutes yield between 93-96%.
2) nanofiltration is concentrated: membrane pressure control adds pure water among 0.5-1.0Mpa, nanofiltration concentration process, adds 0.5-1BV
Water is dialysed, and is down to 1/10 or so to volume, and concentrate unit reaches 60,000-8 ten thousand units, and nanofiltration concentrate conductance is stablized,
Nanofiltration concentration terminates, and condenses liquid yield between 94-97%.
3) active carbon is handled: being controlled at 45-50 DEG C, at stirring by ceramic supernatant volume than 0.3% active carbon, temperature is added
Manage 2h, stand 0.5-1h after stopping stirring, feed liquid squeezes into plate-frame filtering, collect filtrate, OD280 between 10 and 20, filtrate light transmission
Rate > 55%, the yield that decolourizes is in 98-99%.
4) double-effect evaporation: after sheet frame filtrate enters evaporator, temperature is controlled at 80-95 DEG C, is concentrated into theoretical concentration 250,000
More than unit, after there is obvious nucleus, prepare discharging, highest theoretical concentration to ten thousand unit of 40-45, evaporation yield 99-100%.
5) decrease temperature crystalline: concentrate is beaten to crystallizing tank, first uses normal temperature circulation water slow cooling, and midfeather is opened
Stirring after 6h-8h is down to room temperature, opens chilled water, and fast cooling educates brilliant 2-3h to 5-10 DEG C, in material crystal at particle or
Needle-like crystal grain.
6) crystal separates: being filtered using geosyncline or centrifuge carries out crystallized stock separation, separate the later period in geosyncline or centrifugation
In machine, carry out washing crystalline substance with a small amount of 95% ethyl alcohol, until efflux is colorless and transparent, after mother liquor is collected, feed back to crystallizing tank, crystalline mother solution
In ten thousand unit of 0.6-0.8, disposing mother liquor rate is applied to down and criticizes between 3-4% content, is cooled to 5-10 DEG C, secondary crystallization is tied
Brilliant rate of deposition is between 97-98%.
(7) dry: crystal is dried, and into lower road preparation process, or after sieving, original powder is packed.Sample original powder is white
Or pure white, have glossy, granular size is uniform, and mobility is obvious, it is micro- it is lower be systematicness acicular crystal.First drying material is total
Yield is between 85-87%, and original powder content is between 92-95%.
Embodiment 6
1) ceramic clear liquid resin adsorption separation: 2-3 serial column absroption is used, feed flow rate is set as 0.6BV/h early period, and the later period sets
0.4BV/h is set to first to carry out backwash ion-exchange column after saturation absorption with pure water, then start to elute, carried out with 3.5% sodium chloride
Eluent is collected in elution, elutes material mean titre between 2.5 ten thousand -3 ten thousand units, elutes yield between 93-96%.
2) nanofiltration is concentrated: membrane pressure control adds pure water among 0.5-1.0Mpa, nanofiltration concentration process, adds 0.5-1BV
Water is dialysed, and is down to 1/10 or so to volume, and concentrate unit reaches 60,000-8 ten thousand units, and nanofiltration concentrate conductance is stablized,
Nanofiltration concentration terminates, and condenses liquid yield between 94-97%.
3) active carbon is handled: being controlled than 0.5% active carbon, temperature is added at 35 DEG C by ceramic supernatant volume, stir process
3h stands 0.5-1h after stopping stirring, and feed liquid squeezes into plate-frame filtering, collects filtrate, OD280 between 10 and 20, filtrate light transmittance
> 55%, the yield that decolourizes is in 97-98%.
4) double-effect evaporation: after sheet frame filtrate enters evaporator, temperature is controlled at 80-95 DEG C, is concentrated into theoretical concentration 250,000
More than unit, after there is obvious nucleus, prepare discharging, highest theoretical concentration to ten thousand unit of 40-45, evaporation yield 99-100%.
5) decrease temperature crystalline: concentrate is beaten to crystallizing tank, first uses normal temperature circulation water slow cooling, and midfeather unlatching is stirred
It mixes, after 6h-8h is down to room temperature, opens chilled water, fast cooling educates brilliant 2-3h, crystal is at particle or needle in material to 5-10 DEG C
Type crystal grain.
6) crystal separates: being filtered using geosyncline or centrifuge carries out crystallized stock separation, separate the later period in geosyncline or centrifugation
It in machine, carries out washing crystalline substance with a small amount of 95% ethyl alcohol, until efflux is colorless and transparent, crystalline mother solution content is in ten thousand unit of 0.6-0.8, mother liquor
The rate of recovery is between 3-4%, and crystalline deposit rate is between 96-97%.
7) dry: crystal is dried, and into lower road preparation process, or after sieving, original powder is packed.Sample original powder is white
Or pure white, have glossy, granular size is uniform, and mobility is obvious, it is micro- it is lower be systematicness acicular crystal.First drying material is total
Yield is between 83-85%, and original powder content is between 90-93%.
Embodiment 7
1) ceramic clear liquid resin adsorption separation: 2-3 serial column absroption is used, feed flow rate is set as 0.6BV/h early period, and the later period sets
0.3-0.4BV/h is set to first to carry out backwash ion-exchange column after saturation absorption with pure water, then start to elute, with 3.5% sodium chloride
Or ammonium chloride is eluted, and eluent is collected, and elutes material mean titre between 2.5 ten thousand -3 ten thousand units, elutes yield in 93-
Between 96%.
2) nanofiltration is concentrated: membrane pressure control adds pure water among 0.5-1.0Mpa, nanofiltration concentration process, adds 0.5-1BV
Water is dialysed, and is down to 1/10 or so to volume, and concentrate unit reaches 60,000-8 ten thousand units, and nanofiltration concentrate conductance is stablized,
Nanofiltration concentration terminates, and condenses liquid yield between 94-97%.
3) active carbon is handled: being controlled at 40-45 DEG C, at stirring by ceramic supernatant volume than 0.4% active carbon, temperature is added
2-3h is managed, stands 0.5-1h after stopping stirring, feed liquid squeezes into plate-frame filtering, collects filtrate, between 10 and 20, filtrate is saturating by OD280
Light rate > 55%, the yield that decolourizes is in 97-98%.
4) double-effect evaporation: after sheet frame filtrate enters evaporator, temperature is controlled at 80-95 DEG C, is concentrated into theoretical concentration 250,000
More than unit, after there is obvious nucleus, prepare discharging.
5) decrease temperature crystalline: concentrate is beaten to crystallizing tank, first uses normal temperature circulation water slow cooling, and midfeather is opened
Stirring after 6h-8h is down to room temperature, opens chilled water, and fast cooling educates brilliant 2-3h to 5-10 DEG C, in material crystal at particle or
Needle-like crystal grain.
6) crystal separates: being filtered using geosyncline or centrifuge carries out crystallized stock separation, separate the later period in geosyncline or centrifugation
In machine, carry out washing crystalline substance with a small amount of 95% ethyl alcohol, until efflux is colorless and transparent, after mother liquor is collected, feed back to crystallizing tank, crystalline mother solution
In ten thousand unit of 0.6-0.8, disposing mother liquor rate is applied to down and criticizes between 3-4% content, is cooled to 5-10 DEG C, secondary crystallization is tied
Brilliant rate of deposition is between 97-98%.
7) dry: crystal is dried, and into lower road preparation process, or after sieving, original powder is packed.Sample original powder is white
Or pure white, have glossy, granular size is uniform, and mobility is obvious, it is micro- it is lower be systematicness acicular crystal.First drying material is total
Yield is between 85-87%, and original powder content is between 90-93%.
Embodiment 8
1) ceramic clear liquid resin adsorption separation: 2-3 serial column absroption is used, feed flow rate is set as 0.6BV/h early period, and the later period sets
0.3-0.4BV/h is set to first to carry out backwash ion-exchange column after saturation absorption with pure water, then start to elute, with 3.5% sodium chloride
Or ammonium chloride is eluted, and eluent is collected, and elutes material mean titre between 2.5 ten thousand -3 ten thousand units, elutes yield in 93-
Between 96%.
2) nanofiltration is concentrated: membrane pressure control adds pure water among 0.5-1.0Mpa, nanofiltration concentration process, adds 0.5-1BV
Water is dialysed, and is down to 1/10 or so to volume, and concentrate unit reaches 60,000-8 ten thousand units, and nanofiltration concentrate conductance is stablized,
Nanofiltration concentration terminates, and condenses liquid yield between 94-97%.
3) active carbon is handled: being controlled than 0.5% active carbon, temperature is added at 35 DEG C by ceramic supernatant volume, stir process
2-3h stands 0.5-1h after stopping stirring, and feed liquid squeezes into plate-frame filtering, collects filtrate, OD280 between 10 and 20, filtrate light transmission
Rate > 55%, the yield that decolourizes is in 97-98%.
4) double-effect evaporation: after sheet frame filtrate enters evaporator, temperature is controlled at 80-95 DEG C, is concentrated into theoretical concentration 250,000
More than unit, after there is obvious nucleus, small-sized single effect evaporator is gone to, be concentrated into theoretical ten thousand unit of 40-45, prepares discharging.
5) decrease temperature crystalline: concentrate is beaten to crystallizing tank, first uses normal temperature circulation water slow cooling, and midfeather is opened
Stirring after 6h-8h is down to room temperature, opens chilled water, and fast cooling educates brilliant 2-3h, crystal is at uniform in material to 5-10 DEG C
Grain powdery or elongated piece.
6) crystal separates: being filtered using geosyncline or centrifuge carries out crystallized stock separation, separate the later period in geosyncline or centrifugation
It in machine, carries out washing crystalline substance with a small amount of 95% ethyl alcohol, until efflux is colorless and transparent, crystalline mother solution content is in ten thousand unit of 0.6-0.8, mother liquor
The rate of recovery is between 3-4%, and crystalline deposit rate is between 96-97%.
7) dry: crystal is dried, and into lower road preparation process, or after sieving, original powder is packed.Sample original powder is white
Or pure white, have glossy, granular size is uniform, and mobility is obvious, it is micro- it is lower be systematicness acicular crystal.First drying material is total
Yield is between 83-85%, and original powder content is between 90-93%.
Embodiment 9
1) ceramic clear liquid resin adsorption separation: 2-3 serial column absroption is used, feed flow rate is set as 0.6BV/h early period, and the later period sets
0.3-0.4BV/h is set to first to carry out backwash ion-exchange column after saturation absorption with pure water, then start to elute, with 3.5% sodium chloride
Or ammonium chloride is eluted, and eluent is collected, and elutes material mean titre between 2.5 ten thousand -3 ten thousand units, elutes yield in 93-
Between 96%.
2) nanofiltration is concentrated: membrane pressure control adds pure water among 0.5-1.0Mpa, nanofiltration concentration process, adds 0.5-1BV
Water is dialysed, and is down to 1/10 or so to volume, and concentrate unit reaches 60,000-8 ten thousand units, and nanofiltration concentrate conductance is stablized,
Nanofiltration concentration terminates, and condenses liquid yield between 93-95%.
3) active carbon is handled: being controlled at 45-50 DEG C, at stirring by ceramic supernatant volume than 0.4% active carbon, temperature is added
2-3h is managed, stands 0.5-1h after stopping stirring, feed liquid squeezes into plate-frame filtering, collects filtrate, between 10 and 20, filtrate is saturating by OD280
Light rate > 55%, the yield that decolourizes is in 98-99%.
4) double-effect evaporation: after sheet frame filtrate enters evaporator, temperature is controlled at 80-95 DEG C, is concentrated into theoretical concentration 250,000
More than unit, after there is obvious nucleus, small-sized single effect evaporator is gone to, be concentrated into theoretical ten thousand unit of 40-45, prepares discharging.
5) decrease temperature crystalline: concentrate is beaten to crystallizing tank, first uses normal temperature circulation water slow cooling, and midfeather is opened
Stirring, after 6h-8h is down to room temperature, educates brilliant 2-3h.
6) crystal separates: being filtered using geosyncline or centrifuge carries out crystallized stock separation, separate the later period in geosyncline or centrifugation
In machine, carry out washing crystalline substance with a small amount of 95% ethyl alcohol, until efflux is colorless and transparent, after mother liquor is collected, feed back to crystallizing tank, crystalline mother solution
In ten thousand unit of 0.6-0.8, disposing mother liquor rate is applied to down and criticizes between 3-4% content, is cooled to 5-10 DEG C, secondary crystallization is tied
Brilliant rate of deposition is between 97-98%.
7) dry: crystal is dried, and into lower road preparation process, or after sieving, original powder is packed.Sample original powder is white
Or pure white, have glossy, granular size is uniform, and mobility is obvious, it is micro- it is lower be systematicness acicular crystal.First drying material is total
Yield is between 85-87%, and original powder content is between 90-93%.
The above content is combine it is specific/further detailed description of the invention for preferred embodiment, cannot recognize
Fixed specific implementation of the invention is only limited to these instructions.Without departing from the inventive concept of the premise, these have been described
Some replacements or modifications that embodiment is made, all shall be regarded as belonging to protection scope of the present invention.
Claims (10)
1. a kind of preparation method of high-purity kasugarnycin, which is characterized in that successively separated by ceramic clear liquid, resin adsorption,
The step of nanofiltration concentration, active carbon processing, vacuum evaporation, decrease temperature crystalline, crystal separation and drying.
2. preparation method according to claim 1, which is characterized in that include its following processing step:
1) ceramic clear liquid resin adsorption separation: absorption feed flow rate is that 0.3-0.6BV/h is first carried out with pure water after saturation absorption
Backwash ion-exchange column, then starts to elute, and collects eluent；
2) nanofiltration is concentrated: membrane pressure is controlled in 0.5-1.0Mpa, and pure water is added in centre, is down to 1/10 or so to volume, nanofiltration concentration
Terminate；
3) active carbon is handled: being stopped stirring than qualitative activity charcoal, stir process 2-3h is added by ceramic supernatant volume, is stood
0.5-1h, feed liquid are squeezed into sheet frame and are filtered, and filtrate, filtrate light transmittance > 55% are collected；
4) double-effect evaporation: after sheet frame filtrate enters evaporator, temperature is controlled at 80-95 DEG C, after there is obvious nucleus, prepares
Material；
5) decrease temperature crystalline: concentrate is beaten to crystallizing tank, recirculated water slow cooling, and midfeather opens stirring, is cooled to 5-10
DEG C, educate brilliant 2-3h；
6) crystal separates: being filtered using geosyncline or centrifuge carries out crystallized stock separation；
7) dry: crystal is dried, and into lower road preparation process, or after sieving, original powder is packed.
3. preparation method according to claim 2, which is characterized in that in step (1), eluted with 3.5% sodium chloride.
4. preparation method according to claim 2, which is characterized in that in step (2), nanofiltration concentration process, concentrate list
Position reaches 60,000-8 ten thousand units.
5. preparation method according to claim 2, which is characterized in that in step (2), nanofiltration concentration process adds 0.5-
1BV water is dialysed, and control electric conductivity value is relatively stable.
6. preparation method according to claim 2, which is characterized in that in step (3), active carbon treatment process, temperature control
System is at 35-65 DEG C.
7. preparation method according to claim 2, which is characterized in that in step (3), according to feed liquid temperature difference, by body
Active carbon of the product than 0.3-0.5% is added, OD280 10-20, light transmittance are greater than 55%.
8. preparation method according to claim 2, which is characterized in that in step (4), be concentrated by evaporation to theoretical concentration 250,000
It is more than unit, highest theoretical concentration to ten thousand unit of 40-45.
9. preparation method according to claim 2, which is characterized in that in step (5), first slowly dropped using normal temperature circulation water
Temperature after 6h-8h is down to room temperature, opens chilled water, fast cooling is to 5-10 DEG C.
10. preparation method according to claim 2, which is characterized in that in step (6), separate the later period in geosyncline or centrifugation
In machine, carry out washing crystalline substance with a small amount of 95% ethyl alcohol, until efflux is colorless and transparent.
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