CN103641868B - A kind of method utilizing daunorubicin fermentation liquor to produce daunorubicin hydrochloride - Google Patents
A kind of method utilizing daunorubicin fermentation liquor to produce daunorubicin hydrochloride Download PDFInfo
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- 229960003109 daunorubicin hydrochloride Drugs 0.000 title claims abstract description 27
- 238000000855 fermentation Methods 0.000 title claims abstract description 23
- 230000004151 fermentation Effects 0.000 title claims abstract description 23
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- 239000000463 material Substances 0.000 claims description 24
- 239000004695 Polyether sulfone Substances 0.000 claims description 12
- 229920006393 polyether sulfone Polymers 0.000 claims description 12
- 238000001694 spray drying Methods 0.000 claims description 12
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 10
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- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
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- Separation Using Semi-Permeable Membranes (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
Abstract
The present invention relates to a kind of method utilizing daunorubicin fermentation liquor to produce daunorubicin hydrochloride, its technological process is: by pH4 ~ 5, first the daunorubicin fermentation liquor that temperature 50 ~ 60 DEG C and viscosity are less than 600cp adopts porous metal membrane filtration, membrane filtration filtrate uses hollow fiber film assembly ultrafiltration after being cooled to 20 ~ 30 DEG C again, after ultrafiltration, filtrate adopts rolled film nanofiltration process, add acetone after gained nanofiltration filtrate is cooled to 5 ~ 10 DEG C and carry out crystallization, leave standstill after crystal is separated out completely, solid-liquid separation, hydrochloric acid soln is added after the solid daunorubicin purified water washing obtained, to pH4 ~ 6, concentration spraying dry after 20 ~ 25% obtains daunorubicin hydrochloride.The present invention can realize daunorubicin and stablize, produces efficiently.Utilize the method simultaneously, improve extract yield, shorten the production cycle, reduce costs, improve daunorubicin output.
Description
Technical field
The invention belongs to microbiotic extraction, synthesis technical field, particularly relate to a kind of method utilizing daunorubicin fermentation liquor to produce daunorubicin hydrochloride.
Background technology
Daunorubicin has another name called zhengdingmeisu, is a kind of very important antitumor drug in anthracycline antibiotics.Main in order to treat acute leukemia clinically, to acute lymphoblastic leukemia and acute myeloblastic leukemia, daunorubicin can be used as choice drug, but suitable and other drug conbined usage.Daunorubicin can also treat lymphosarcoma, neuroblastoma, rhabdosarcoma etc.
At present, the domestic documents and materials for daunorubicin extraction process report are less.Domesticly declare the patent of invention using absorption with macroporous adsorbent resin and elution technique Isolation and purification daunorubicin, but the subject matter existed is that fermented liquid need through pre-treatment, and purifying and extraction production technology route complexity, extend the production time, product yield is on the low side, general about 70%, cause production cost high.
Summary of the invention
The object of the invention is just the defect overcoming above-mentioned prior art, there is provided one effectively to improve product yield, shorten the production time, reduce costs, reduce environmental pollution, realize that daunorubicin is stablized, the daunorubicin fermentation liquor that utilizes of High-efficient Production produces the method for daunorubicin hydrochloride.
Technical scheme taked for achieving the above object is:
A kind of method utilizing daunorubicin fermentation liquor to produce daunorubicin hydrochloride, it is characterized in that its technological process is: by pH4 ~ 5, first the daunorubicin fermentation liquor that temperature 50 ~ 60 DEG C and viscosity are less than 600cp adopts porous metal membrane filtration, membrane filtration filtrate uses hollow fiber film assembly ultrafiltration after being cooled to 20 ~ 30 DEG C again, after ultrafiltration, filtrate adopts rolled film nanofiltration process, add acetone after gained nanofiltration filtrate is cooled to 5 ~ 10 DEG C and carry out crystallization, leave standstill after crystal is separated out completely, solid-liquid separation, hydrochloric acid soln is added after the solid daunorubicin purified water washing obtained, to pH4 ~ 6, concentration spraying dry after 20 ~ 25% obtains daunorubicin hydrochloride.
Described porous metal membrane filtration adopts cross-flow mode to carry out circulating filtration, pressure-controlling 0.1 ~ 0.2MPa; In membrane filtration processes, add water-dialyzing, this water-dialyzing is the filtrate of daunorubicin membrane filtration, when the filtrate volume of membrane filtration first reaches 10 ~ 20% of fermentating liquid volume, as water-dialyzing after being diluted 3 ~ 5 times, join in fermented liquid, operate continuously 2 ~ 3 times.
Described porous metal membrane material is titanium dioxide or stainless steel membrane, and aperture is 0.1 μm.
In described ultra-filtration process, pressure-controlling is at 0.1 ~ 0.2MPa, and the material of hollow-fibre membrane used is polyethersulfone or polymeric amide, and it can the material of molecular weight cut-off more than 800.
In described nanofiltration process, pressure-controlling is at 1 ~ 1.2MPa, and the flow rate control of nanofiltration is at 400 ~ 500L/h, and the concentrated volume multiple of nanofiltration is 3 ~ 5 times; Nanofiltration terminates, and adopts purified water top to wash 5 ~ 10min; The material of rolled film used is polyethersulfone, and aperture is 0.5nm, can the material of molecular weight cut-off more than 300.
During described crystallization, the add-on of acetone is 5 ~ 10 times of nanofiltration filtrate volume.
Described solid daunorubicin purified water washes 2 times, and the consumption of each purified water is solid daunorubicin weight 3 ~ 5 times.
The mass concentration of described hydrochloric acid soln is 10 ~ 30%.
In described spray-drying process, control inlet temperature 140 ~ 150 DEG C, air outlet temperature 50 ~ 60 DEG C, feed rotation is 150 ~ 180r/min.
Technique effect of the present invention:
1) final product quality meets 2010 editions Chinese Pharmacopoeias.
2) yield of finished product is more than 85%.
3) adopt membrane technique to extract daunorubicin, achieve minimizing process procedure, shorten the production time, the target reduced costs.
4) production cost is reduced.
Embodiment
Be explained the present invention with example below, it should be understood that example is for illustration of the present invention instead of limitation of the present invention.Scope of the present invention and core content are determined according to claims.
In the present invention, daunorubicin fermentation liquor utilizes ripple plug streptomycete or streptomyces coeruleorubidus, to adopt three grade fermemtation mode of manufacture, its substratum and composition respectively: carbon source mainly W-Gum, the wheat bran of daunorubicin substratum; Organic nitrogen source is protein powder, peptone and soybean cake powder mainly; Inorganic nitrogen-sourced mainly ammonium sulfate; Inorganic salt are potassium primary phosphate, calcium carbonate and sodium-chlor mainly.
embodiment 1
Daunorubicin fermentation liquor is tired 3.43g/L, and volume is 10m
3.Start fermentor tank to stir, rotating speed controls at 10r/min, with the salt acid for adjusting pH to 4.1 of 20%, then fermented liquid is warming up to 75 ~ 76 DEG C, continues to stir 20min.Add tap water dilution fermented liquid, its viscosity is 576cp, solid content 9.3%, total reducing sugar 1.72%, amino nitrogen 1.85%.In dilution, the temperature of fermented liquid controls at 50 ~ 52 DEG C.
Select porous metal membrane filter plant, membrane material is titanium dioxide, and aperture is 0.1 μm.
Cross-flow mode is adopted to carry out circulating filtration, pressure-controlling 0.1 ~ 0.2MPa.Membrane filtration filtrate ingress mounting heat exchanger, filtrate temperature controls, at 50 ~ 52 DEG C, in membrane filtration processes, to add water-dialyzing, and its source is the filtrate of daunorubicin membrane filtration, when the filtrate volume of membrane filtration first reaches 1m
3time, as water-dialyzing after being diluted 3 times, operate continuously like this 2 times.Membrane filtration terminates, and tires as 2.33g/L, and volume is 14.3m
3, yield is 97.3%.
Filtrate temperature through membrane filtration is down to 20 ~ 22 DEG C, and then filtrate enters ultrafiltration apparatus, and the assembly of its film is hollow-fibre membrane, and material is polyethersulfone.In ultra-filtration process, pressure-controlling is at 0.1 ~ 0.2MPa.Ultrafiltration terminates, and filtrate volume is 14.1m
3, tire as 2.32g/L, yield is 98.2%.
Filtrate after ultrafiltration is by nanofiltration equipment.Nanofiltration membrane adopts rolled film, and its material is polyethersulfone, and aperture is 0.5nm.In nanofiltration process, pressure-controlling is at 1 ~ 1.2MPa, and filtrate temperature controls at 20 ~ 22 DEG C, and the flow rate control of nanofiltration is at 400 ~ 420L/h.The concentrated volume multiple of nanofiltration is 3 times.Nanofiltration terminates, and adopts purified water top to wash 5min.Its filtrate volume is 5.2m
3, tire as 6.24g/L, yield is 99.3%.
Start and stir, rotating speed controls at 10r/min, and the filtrate temperature through nanofiltration is down to 8 ~ 10 DEG C, adds acetone, and its add-on is 5 times of filtrate volume.Crystal leaves standstill 1h after separating out.Leave standstill after terminating and carry out solid-liquid separation, the solid daunorubicin purified water obtained washes 2 times, and the consumption of each purified water is solid daunorubicin weight 3 times.Crystallization terminates, and daunorubicin solid weight is 31.3kg, and crystallization yield is 96.4%.
With the hydrochloric acid soln of purified water configuration 10%, join in the reactor that daunorubicin crystal is housed, start and stir, regulate pH to 4.2, its concentration is controlled 20%.Then this daunorubicin hydrochloride solution is entered spray-drying tower.In spray-drying process, control inlet temperature 140 ~ 150 DEG C, air outlet temperature 50 ~ 60 DEG C, feed rotation is 150 ~ 180r/min.Spraying dry terminates, and obtains solid daunorubicin hydrochloride 32.8kg, and yield is 97.2%.
Daunorubicin extracts, the total recovery of synthesis is about 88.9%.
embodiment 2
Daunorubicin fermentation liquor is tired 3.21g/L, and volume is 10m
3.Start fermentor tank to stir, rotating speed controls at 15r/min, with the salt acid for adjusting pH to 4.3 of 20%, then fermented liquid is warming up to 77 ~ 78 DEG C, continues to stir 22min.Add tap water dilution fermented liquid, its viscosity is 560cp, solid content 8.9%, total reducing sugar 1.63%, amino nitrogen 1.78%.In dilution, the temperature of fermented liquid controls at 53 ~ 54 DEG C.
Select porous metal membrane filter plant, membrane material is
stainless steel, aperture is 0.1 μm.
Cross-flow mode is adopted to carry out circulating filtration, pressure-controlling 0.1 ~ 0.2MPa.Membrane filtration filtrate ingress mounting heat exchanger, filtrate temperature controls, at 53 ~ 54 DEG C, in membrane filtration processes, to add water-dialyzing, and its source is the filtrate of daunorubicin membrane filtration, when the filtrate volume of membrane filtration first reaches 1m
3time, as dialyzate after being diluted 3.5 times, operate continuously like this 2 times.Membrane filtration terminates, and tires as 2.11g/L, and volume is 14.8m
3, yield is 97.7%.
Filtrate temperature through membrane filtration is down to 23 ~ 24 DEG C, and then filtrate enters ultrafiltration apparatus, and the assembly of its film is hollow-fibre membrane, and material is polymeric amide.In ultra-filtration process, pressure-controlling is at 0.1 ~ 0.2MPa.Ultrafiltration terminates, and filtrate volume is 14.6m
3, tire as 2.09g/L, yield is 98.2%.
Filtrate after ultrafiltration is by nanofiltration equipment.Nanofiltration membrane adopts rolled film, and its material is polyethersulfone, and aperture is 0.5nm.In nanofiltration process, pressure-controlling is at 1 ~ 1.2MPa, and filtrate temperature controls at 23 ~ 24 DEG C, and the flow rate control of nanofiltration is at 430 ~ 440L/h.The concentrated volume multiple of nanofiltration is 3.5 times.Nanofiltration terminates, and adopts purified water top to wash 6min.Its filtrate volume is 4.6m
3, tire as 6.59g/L, yield is 99.4%.
Start and stir, rotating speed controls at 12r/min, and the filtrate temperature through nanofiltration is down to 7 ~ 8 DEG C, adds acetone, and its add-on is 6 times of filtrate volume.Crystal leaves standstill 1h after separating out.Leave standstill after terminating and carry out solid-liquid separation, the solid daunorubicin purified water obtained washes 2 times, and the consumption of each purified water is solid daunorubicin weight 3.5 times.Crystallization terminates, and daunorubicin solid weight is 29.28kg, and crystallization yield is 96.6%.
With the hydrochloric acid soln of purified water configuration 15%, join in the reactor that daunorubicin crystal is housed, start and stir, regulate pH to 4.7, its concentration is controlled 22%.Daunorubicin hydrochloride solution enters spray-drying tower.In spray-drying process, control inlet temperature 140 ~ 150 DEG C, air outlet temperature 50 ~ 60 DEG C, feed rotation is 150 ~ 180r/min.Spraying dry terminates, and obtains solid daunorubicin hydrochloride 30.55kg, and yield is 97.6%.
Daunorubicin extracts, the total recovery of synthesis is about 89.9%.
embodiment 3
Daunorubicin fermentation liquor is tired 3.18g/L, and volume is 10m
3.Start fermentor tank to stir, rotating speed controls at 20r/min, with the salt acid for adjusting pH to 4.5 of 20%, then fermented liquid is warming up to 79 ~ 81 DEG C, continues to stir 25min.Add tap water dilution fermented liquid, its viscosity is 551cp, solid content 8.6%, total reducing sugar 1.60%, amino nitrogen 1.72%.In dilution, the temperature of fermented liquid controls at 55 ~ 56 DEG C.
Select porous metal membrane filter plant, membrane material is titanium dioxide, and aperture is 0.1 μm.
Cross-flow mode is adopted to carry out circulating filtration, pressure-controlling 0.1 ~ 0.2MPa.Membrane filtration filtrate ingress mounting heat exchanger, filtrate temperature controls, at 55 ~ 56 DEG C, in membrane filtration processes, to add water-dialyzing, and its source is the filtrate of daunorubicin membrane filtration, when the filtrate volume of membrane filtration first reaches 1.5m
3time, as water-dialyzing after being diluted 4 times, operate continuously 3 times.Membrane filtration terminates, and tires as 1.70g/L, and volume is 18.3m
3, yield is 97.9%.
Filtrate temperature through membrane filtration is down to 24 ~ 26 DEG C, and then filtrate enters ultrafiltration apparatus, and the assembly of its film is hollow-fibre membrane, and material is polyethersulfone.In ultra-filtration process, pressure-controlling is at 0.1 ~ 0.2MPa.Ultrafiltration terminates, and filtrate volume is 18.1m
3, tire as 1.69g/L, yield is 98.5%.
Filtrate after ultrafiltration is by nanofiltration equipment.Nanofiltration membrane adopts rolled film, and its material is polyethersulfone, and aperture is 0.5nm.In nanofiltration process, pressure-controlling is at 1 ~ 1.2MPa, and filtrate temperature controls at 24 ~ 25 DEG C, and the flow rate control of nanofiltration is at 440 ~ 460L/h.The concentrated volume multiple of nanofiltration is 4 times.Nanofiltration terminates, and adopts purified water top to wash 7min.Its filtrate volume is 4.9m
3, tire as 6.21g/L, yield is 99.5%.
Start and stir, rotating speed controls at 15r/min, and the filtrate temperature through nanofiltration is down to 6 ~ 7 DEG C, adds acetone, and its add-on is 7 times of filtrate volume.Crystal leaves standstill 1h after separating out.Leave standstill after terminating and carry out solid-liquid separation, the solid daunorubicin purified water obtained washes 2 times, and the consumption of each purified water is solid daunorubicin weight 4 times.Crystallization terminates, and daunorubicin solid weight is 29.58kg, and crystallization yield is 97.2%.
With the hydrochloric acid soln of purified water configuration 20%, join in the reactor that daunorubicin crystal is housed, start and stir, regulate pH to 5.1, its concentration is controlled 23%.Daunorubicin hydrochloride solution enters spray-drying tower.In spray-drying process, control inlet temperature 140 ~ 150 DEG C, air outlet temperature 50 ~ 60 DEG C, feed rotation is 150 ~ 180r/min.Spraying dry terminates, and obtains solid daunorubicin hydrochloride 30.90kg, and yield is 97.7%.
Daunorubicin extracts, the total recovery of synthesis is about 91.1%.
embodiment 4
Daunorubicin fermentation liquor is tired 3.22g/L, and volume is 10m
3.Start fermentor tank to stir, rotating speed controls at 25r/min, with the salt acid for adjusting pH to 4.7 of 20%, then fermented liquid is warming up to 82 ~ 83 DEG C, continues to stir 27min.Add tap water dilution fermented liquid, its viscosity is 541cp, solid content 8.1%, total reducing sugar 1.52%, amino nitrogen 1.63%.In dilution, the temperature of fermented liquid controls at 56 ~ 57 DEG C.
Select porous metal membrane filter plant, membrane material is
stainless steel, aperture is 0.1 μm.
Cross-flow mode is adopted to carry out circulating filtration, pressure-controlling 0.1 ~ 0.2MPa.Membrane filtration filtrate ingress mounting heat exchanger, filtrate temperature controls, at 56 ~ 57 DEG C, in membrane filtration processes, to add water-dialyzing, and its source is the filtrate of daunorubicin membrane filtration, when the filtrate volume of membrane filtration first reaches 1.5m
3time, diluted 4.5 times as water-dialyzing, operate continuously 2 times.Membrane filtration terminates, and tires as 1.88g/L, and volume is 16.7m
3, yield is 97.4%.
Filtrate temperature through membrane filtration is down to 27 ~ 28 DEG C, and then filtrate enters ultrafiltration apparatus, and the assembly of its film is hollow-fibre membrane, and material is polymeric amide.In ultra-filtration process, pressure-controlling is at 0.1 ~ 0.2MPa.Ultrafiltration terminates, and filtrate volume is 16.3m
3, tire as 1.89g/L, yield is 98.2%.
Filtrate after ultrafiltration is by nanofiltration equipment.Nanofiltration membrane adopts rolled film, and its material is polyethersulfone, and aperture is 0.5nm.In nanofiltration process, pressure-controlling is at 1 ~ 1.2MPa, and filtrate temperature controls at 26 ~ 27 DEG C, and the flow rate control of nanofiltration is at 460 ~ 480L/h.The concentrated volume multiple of nanofiltration is 4.5 times.Nanofiltration terminates, and adopts purified water top to wash 8min.Its filtrate volume is 4.1m
3, tire as 7.45g/L, yield is 99.2%.
Start and stir, rotating speed controls at 17r/min, and the filtrate temperature through nanofiltration is down to 5 ~ 6 DEG C, adds acetone, and its add-on is 8 times of filtrate volume.Crystal leaves standstill 1h after separating out.Leave standstill after terminating and carry out solid-liquid separation, the solid daunorubicin purified water obtained washes 2 times, and the consumption of each purified water is solid daunorubicin weight 4.5 times.Crystallization terminates, and daunorubicin solid weight is 29.6kg, and crystallization yield is 97.0%.
With the hydrochloric acid soln of purified water configuration 25%, join in the reactor that daunorubicin crystal is housed, start and stir, regulate pH to 5.5, its concentration is controlled 24%.Daunorubicin hydrochloride solution enters spray-drying tower.In spray-drying process, control inlet temperature 140 ~ 150 DEG C, air outlet temperature 50 ~ 60 DEG C, feed rotation is 150 ~ 180r/min.Spraying dry terminates, and obtaining solid daunorubicin hydrochloride 30.8kg yield is 97.4%.
Daunorubicin extracts, the total recovery of synthesis is about 89.6%.
embodiment 5
Daunorubicin fermentation liquor is tired 3.08g/L, and volume is 10m
3.Start fermentor tank to stir, rotating speed controls at 30r/min, with the salt acid for adjusting pH to 4.9 of 20%, then fermented liquid is warming up to 83 ~ 85 DEG C, continues to stir 30min.Add tap water dilution fermented liquid, its viscosity is 532cp, solid content 7.8%, total reducing sugar 1.47%, amino nitrogen 1.58%.In dilution, the temperature of fermented liquid controls at 58 ~ 60 DEG C.
Select porous metal membrane filter plant, membrane material is titanium dioxide, and aperture is 0.1 μm.
Cross-flow mode is adopted to carry out circulating filtration, pressure-controlling 0.1 ~ 0.2MPa.Membrane filtration filtrate ingress mounting heat exchanger, filtrate temperature controls, at 58 ~ 60 DEG C, in membrane filtration processes, to add water-dialyzing, and its source is the filtrate of daunorubicin membrane filtration, when the filtrate volume of membrane filtration first reaches 2m
3time, diluted 5 times as water-dialyzing, operate continuously 3 times.Membrane filtration terminates, and tires as 1.27g/L, and volume is 23.6m
3, yield is 97.1%.
Filtrate temperature through membrane filtration is down to 29 ~ 30 DEG C, and then filtrate enters ultrafiltration apparatus, and the assembly of its film is hollow-fibre membrane, and material is polyethersulfone.In ultra-filtration process, pressure-controlling is at 0.1 ~ 0.2MPa.Ultrafiltration terminates, and filtrate volume is 23.3m
3, tire as 1.26g/L, yield is 98.3%.
Filtrate after ultrafiltration is by nanofiltration equipment.Nanofiltration membrane adopts rolled film, and its material is polyethersulfone, and aperture is 0.5nm.In nanofiltration process, pressure-controlling is at 1 ~ 1.2MPa, and filtrate temperature controls at 28 ~ 30 DEG C, and the flow rate control of nanofiltration is at 480 ~ 500L/h.The concentrated volume multiple of nanofiltration is 5 times.Nanofiltration terminates, and adopts purified water top to wash 10min.Its filtrate volume is 5.3m
3, tire as 5.48g/L, yield is 99.0%.
Start and stir, rotating speed controls at 20r/min, and the filtrate temperature through nanofiltration is down to 5 ~ 6 DEG C, adds acetone, and its add-on is 10 times of filtrate volume.Crystal leaves standstill 1h after separating out.Leave standstill after terminating and carry out solid-liquid separation, the solid daunorubicin purified water obtained washes 3 times, and the consumption of each purified water is solid daunorubicin weight 5 times.Crystallization terminates, and daunorubicin solid weight is 28.2kg, and crystallization yield is 97.2%.
With the hydrochloric acid soln of purified water configuration 30%, join in the reactor that daunorubicin crystal is housed, start and stir, regulate pH to 5.5, its concentration is controlled 24%.Daunorubicin hydrochloride solution enters spray-drying tower.In spray-drying process, control inlet temperature 140 ~ 150 DEG C, air outlet temperature 50 ~ 60 DEG C, feed rotation is 150 ~ 180r/min.Spraying dry terminates, and obtains solid daunorubicin hydrochloride 29.3kg, and yield is 97.1%.
Daunorubicin extracts, the total recovery of synthesis is about 88.9%.
Claims (8)
1. the method utilizing daunorubicin fermentation liquor to produce daunorubicin hydrochloride, it is characterized in that its technological process is: by pH4 ~ 5, first the daunorubicin fermentation liquor that temperature 50 ~ 60 DEG C and viscosity are less than 600cp adopts porous metal film to carry out circulating filtration with cross-flow mode, pressure-controlling 0.1 ~ 0.2MPa, in membrane filtration processes, add water-dialyzing, this water-dialyzing is the filtrate of daunorubicin membrane filtration, when the filtrate volume of membrane filtration first reaches 10 ~ 20% of fermentating liquid volume, as water-dialyzing after being diluted 3 ~ 5 times, join in fermented liquid, operate continuously 2 ~ 3 times, afterwards, hollow fiber film assembly ultrafiltration is used again after membrane filtration filtrate is cooled to 20 ~ 30 DEG C, after ultrafiltration, filtrate adopts rolled film nanofiltration process, add acetone after gained nanofiltration filtrate is cooled to 5 ~ 10 DEG C and carry out crystallization, standing, solid-liquid separation after crystal is separated out completely, add hydrochloric acid soln after the solid daunorubicin purified water washing obtained, to pH4 ~ 6, concentration spraying dry after 20 ~ 25% obtain daunorubicin hydrochloride.
2., according to the method utilizing daunorubicin fermentation liquor to produce daunorubicin hydrochloride according to claim 1, it is characterized in that described porous metal membrane material is titanium dioxide or stainless steel membrane, aperture is 0.1 μm.
3., according to the method utilizing daunorubicin fermentation liquor to produce daunorubicin hydrochloride according to claim 1, it is characterized in that in described ultra-filtration process, pressure-controlling is at 0.1 ~ 0.2MPa, and the material of hollow-fibre membrane used is polyethersulfone or polymeric amide.
4. according to the method utilizing daunorubicin fermentation liquor to produce daunorubicin hydrochloride according to claim 1, it is characterized in that in described nanofiltration process, pressure-controlling is at 1 ~ 1.2MPa, and the flow rate control of nanofiltration is at 400 ~ 500L/h, and the concentrated volume multiple of nanofiltration is 3 ~ 5 times; Nanofiltration terminates, and adopts purified water top to wash 5 ~ 10min; The material of rolled film used is polyethersulfone, and aperture is 0.5nm.
5., according to the method utilizing daunorubicin fermentation liquor to produce daunorubicin hydrochloride according to claim 1, when it is characterized in that described crystallization, the add-on of acetone is 5 ~ 10 times of nanofiltration filtrate volume.
6., according to the method utilizing daunorubicin fermentation liquor to produce daunorubicin hydrochloride according to claim 1, it is characterized in that described solid daunorubicin purified water washes 2 times, the consumption of each purified water is solid daunorubicin weight 3 ~ 5 times.
7., according to the method utilizing daunorubicin fermentation liquor to produce daunorubicin hydrochloride according to claim 1, it is characterized in that the mass concentration of described hydrochloric acid soln is 10 ~ 30%.
8., according to the method utilizing daunorubicin fermentation liquor to produce daunorubicin hydrochloride according to claim 1, it is characterized in that in described spray-drying process, control inlet temperature 140 ~ 150 DEG C, air outlet temperature 50 ~ 60 DEG C, feed rotation is 150 ~ 180r/min.
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