CN106350550B - A method of phenol sodium is examined from Mycophenolic Acid bacterial strain preparation wheat - Google Patents
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Abstract
The present invention provides a kind of methods for examining phenol sodium from Mycophenolic Acid bacterial strain preparation wheat, comprising: takes Mycophenolic Acid bacterial strain producing strains spore suspension, is inoculated on seed culture medium and cultivates 2~4 days at 26~28 DEG C；Seed culture medium is inoculated in fermentor and adds fermentation medium, ferments 9~11 days at 26~28 DEG C；Acid is added into fermentation liquid makes the pH of fermentation liquid in 3~4, and sodium hydroxide solution is then added into fermentation liquid makes the pH of fermentation liquid be in 8~9, obtains Mycophenolic Acid after decoloration recrystallization；Mycophenolic Acid and sodium hydroxide or sodium methoxide are synthesized wheat in alcohols solvent and examine phenol sodium.In the present invention, fermentation liquid Mai Kaofen acid bacterial strain obtained after culture is handled by soda acid, and is synthetically generated wheat with sodium hydroxide or sodium methoxide and is examined phenol sodium, has preparation route short, operation sequence is simple, the lower advantage of manufacturing cost；Meanwhile avoiding reducing harm to environment and human body using organic solvent of ketone.
Description
Technical field
The present invention relates to biopharmaceutical technology more particularly to a kind of sides that phenol sodium is examined from Mycophenolic Acid bacterial strain preparation wheat
Method.
Background technique
Wheat examines phenol sodium also known as mycophenolate sodium, be it is a kind of from Mycophenolic Acid by the obtained immunosuppressor of synthesis, molecular formula:
C17H19NaO6, molecular weight: 342.3.Wheat is examined shown in the chemical structural formula such as following formula (1) of phenol sodium.
Wheat examines the sodium salt that phenol sodium (MPS) is Mycophenolic Acid (MPA).Mycophenolic Acid is a kind of selective, noncompetitive, reversible
Hypoxanthine monophosphate dehydrogenase (IMPDH) inhibitor, be able to suppress the classical route of synthesis of guanylic acid without damaging
Hurt the synthesis of DNA.Wheat examine phenol sodium be suitable for shared with cyclosporine and corticosteroid, for receive allograft renal transplantation at
The prevention of year patients acuity rejection.The research and development and application of immunosuppressor are that one in organ transplant development history is important
Milestone, it promotes and has pushed the raising of clinical renal transplantation quantity and the improvement of quality.Kidney transplant is set to become current because each
Kind primary disease causes the conventional treatments of renal failure.
Currently, it mainly includes solid state fermentation and liquid fermentation method that preparation wheat, which examines phenol sodium,.But there is conjunction in solid state fermentation
At the low defect of stability.Phase, culture medium can be collapsed collapse and be hardened liquid fermentation method after incubation, be unfavorable for mass transfer and passed
Heat.The Chinese invention patent of notification number CN101348810B discloses " solid state fermentation of Mai Kaofen acid ", needs using non-
Inert carrier.This non-inert carrier is crossed in industrial application can generate a large amount of waste material in vehicle, cause so as to cause to environment
Certain pollution；On the other hand this it is existing whole product " wheat examines phenol sodium " also can not directly be prepared, so as to cause synthetic route compared with
It is long.Meanwhile in current liquid fermentation method, the metabolite and microbial environment of microbial cell can also examine wheat phenol sodium
Precursor (i.e. " Mycophenolic Acid ") causes adverse effect.
In view of this, it is necessary to which the preparation method for examining phenol sodium to wheat in the prior art is improved, to solve above-mentioned ask
Topic.
Summary of the invention
It is an object of the invention to disclose a kind of method for examining phenol sodium from Mycophenolic Acid bacterial strain preparation wheat, shorten to realize
Synthetic route reduces manufacturing cost, and generated byproduct is to dirt caused by environment during reduction preparation wheat examines phenol sodium
Dye, and improve reproducibility.
For achieving the above object, the present invention provides the methods for examining phenol sodium from Mycophenolic Acid bacterial strain preparation wheat, including
Following steps:
Step (1) takes Mycophenolic Acid bacterial strain producing strains spore suspension, is inoculated on seed culture medium at 26~28 DEG C
Culture 2~4 days；
Step (2), seed culture medium are inoculated in fermentor and add fermentation medium, fermentation 9~11 at 26~28 DEG C
It, carries out putting tank after fermentation to extract fermentation liquid；
Step (3) adds the sour pH for making fermentation liquid into fermentation liquid in 3~4, and sodium hydroxide is then added into fermentation liquid
Solution makes the pH of fermentation liquid in 8~9, and plate-frame filtering, filtrate is adjusted to pH in 2~3 with acid again, and filtering obtains Mycophenolic Acid crude product,
Mycophenolic Acid crude product is dissolved in alcohols solvent rear decoloring, obtains Mycophenolic Acid after recrystallization；
Mycophenolic Acid and sodium hydroxide or sodium methoxide are synthesized in alcohols solvent wheat and examine phenol sodium by step (4), wherein anti-
Answering temperature is 40~60 DEG C, the reaction time 1~3 hour；
Step (5) crystallizes after the reaction solution that step (4) obtains is concentrated, and filters, dry.
As a further improvement of the present invention, the composition of the seed culture medium in the step (1) are as follows: soybean cake powder 5~
15g/L, 40~60g/L of lactose, 20~40g/L of Dried Corn Steep Liquor Powder, 1~3g/L of ammonium nitrate, 1~3g/L of potassium dihydrogen phosphate, carbonic acid
1~3g/L of calcium.
As a further improvement of the present invention, the composition of the fermentation medium in the step (2) are as follows: soybean cake powder 15~
25g/L, 5~15g/L of cornstarch, 45~65g/L of glucose, 70~90g/L of fructose, 45~55g/L of Dried Corn Steep Liquor Powder, carbonic acid
1~3g/L of calcium, 2~4g/L of methionine, 0.5~1.5g/L of potassium dihydrogen phosphate.
As a further improvement of the present invention, the acid in the step (3) be selected from hydrochloric acid or sulfuric acid, concentration be 6~
12mol/L, the alcohols solvent in the step (3) are selected from ethyl alcohol or methanol.
As a further improvement of the present invention, the alcohols solvent in the step (4) be selected from methanol, ethyl alcohol, normal propyl alcohol or
N-butanol.
As a further improvement of the present invention, the crystallization mode in the step (5) is condensing crystallizing or crystallisation by cooling；Its
In, the temperature of condensing crystallizing is 40~60 DEG C, and the temperature of crystallisation by cooling is 0~10 DEG C.
As a further improvement of the present invention, the drying mode in the step (5) is vacuum drying, vacuum drying temperature
Degree is 40~50 DEG C, and vacuum drying vacuum degree is 0.1~0.5MPa.
Compared with prior art, the beneficial effects of the present invention are: in the present invention, Mai Kaofen acid bacterial strain obtains after culture
The fermentation liquid arrived is handled by soda acid, and is synthetically generated wheat with sodium hydroxide or sodium methoxide and is examined phenol sodium, has preparation route short,
Operation sequence is simple, the lower advantage of manufacturing cost；Meanwhile it avoiding reducing using organic solvent of ketone to environment and human body
Harm.
Specific embodiment
Below with reference to each embodiment, the present invention is described in detail, but it should be stated that, these embodiments are simultaneously
Non- limitation of the present invention, those of ordinary skill in the art are according to these embodiments in made function, method or structure
Equivalent transformation or substitution, all belong to the scope of protection of the present invention within.
Unless there is specified otherwise in specification, it is pure that the component in each embodiment in the present invention, raw material are all made of analysis
Rank.In addition, " g " in each embodiment is unit of weight " gram "；" h " is chronomere " hour "；" ml " is volume unit " milli
It rises "；" room temperature " is 23 DEG C；" HPLC " is " high performance liquid chromatography ".
Embodiment one:
This includes the following steps from the method that Mycophenolic Acid bacterial strain preparation wheat examines phenol sodium.
Step (1) takes Mycophenolic Acid producing strains spore suspension, is inoculated on seed culture medium, cultivates 4 days at 28 DEG C.It should
Each group in seed culture medium is divided into (unit: g/L): soybean cake powder 5, lactose 40, Dried Corn Steep Liquor Powder 20, ammonium nitrate 1, di(2-ethylhexyl)phosphate
Hydrogen potassium 1, calcium carbonate 1, surplus are water.
Step (2), seed culture medium are inoculated in fermentor and add fermentation medium, and 26 DEG C are cultivated 10 days.Fermentation training
Support each component (unit: g/L) in base: soybean cake powder 15, cornstarch 5, glucose 45, fructose 70, Dried Corn Steep Liquor Powder 45, carbon
Sour calcium 1, methionine 2, potassium dihydrogen phosphate 0.5, surplus are water.It carries out putting tank after fermentation to extract fermentation liquid.
Step (3), into fermentation liquid, addition acid makes fermentation liquid be acidified to pH in 3.0, and hydrogen-oxygen is then added into fermentation liquid
Changing sodium solution makes the pH of fermentation liquid in 8.0.Plate-frame filtering, filtrate are adjusted to pH in 2.0 with acid again, and it is thick to obtain Mycophenolic Acid for filtering
Product；Mycophenolic Acid crude product is dissolved in alcohols solvent rear decoloring, obtains Mycophenolic Acid after recrystallization.In the present embodiment, acid used
The dilute sulfuric acid for being 10wt% for mass concentration.
Mycophenolic Acid and sodium hydroxide are carried out synthetic reaction in methanol by step (4), examine phenol sodium, reaction temperature to generate wheat
50 DEG C, the reaction time 2 hours of degree.
Step (5), by step (4) reaction solution crystallize, filtering is dry to examine phenol sodium to get whole product wheat.In the present embodiment
In, crystallization mode is 0 DEG C of crystallisation by cooling.40 DEG C of drying temperature.
Through Physico-chemical tests, fusing point meets as defined in pertinent literature solid obtained by the present embodiment (i.e. " wheat examines phenol sodium ")
189~191 DEG C, and fusing point is 189.5~190.1 DEG C, is detected through HPLC, the purity that the wheat as made from this method examines phenol sodium is
99.91%.
Embodiment two:
This includes the following steps from the method that Mycophenolic Acid bacterial strain preparation wheat examines phenol sodium.
Step (1) takes Mycophenolic Acid producing strains spore suspension, is inoculated on culture medium, cultivates 3 days at 26 DEG C；The seed
Each group in culture medium is divided into (unit: g/L): soybean cake powder 10, lactose 50, Dried Corn Steep Liquor Powder 25, ammonium nitrate 2, biphosphate
Potassium 2, calcium carbonate 2, surplus are water.
Step (2), seed culture medium are inoculated in fermentor and add fermentation medium, and 26 DEG C are cultivated 9 days.Fermented and cultured
Each group in base is divided into (unit: g/L): soybean cake powder 20, cornstarch 10, glucose 50, fructose 80, Dried Corn Steep Liquor Powder 50,
Calcium carbonate 1, methionine 3, potassium dihydrogen phosphate 0.5, surplus are water.It carries out putting tank after fermentation to extract fermentation liquid.
Step (3), into fermentation liquid, addition acid makes fermentation liquid be acidified to pH in 4.0, and hydrogen-oxygen is then added into fermentation liquid
Changing sodium solution makes the pH of fermentation liquid in 9.0.Plate-frame filtering, filtrate are adjusted to pH in 3.0 with acid again, and it is thick to obtain Mycophenolic Acid for filtering
Product；Mycophenolic Acid crude product is dissolved in alcohols solvent rear decoloring, obtains Mycophenolic Acid after recrystallization.In the present embodiment, acid used
The dilute sulfuric acid for being 5wt% for mass concentration.
Mycophenolic Acid and sodium hydroxide are carried out synthetic reaction in ethyl alcohol to produce wheat and examine phenol sodium, reaction temperature by step (4)
40 DEG C, the reaction time 3 hours of degree.
Step (5), the reaction solution for obtaining step (4) are concentrated, and crystallization is dry to examine phenol sodium to get whole product wheat.Crystallization mode
For 40 DEG C of condensing crystallizings.Vacuum drying temperature is 40 DEG C, and vacuum drying vacuum degree is 0.1MPa.
For solid obtained by the present embodiment (i.e. " wheat examines phenol sodium ") through Physico-chemical tests, fusing point meets pertinent literature regulation 189
~191 DEG C, fusing point is 189.9~190.5 DEG C, is detected through HPLC, the purity that the wheat as made from this method examines phenol sodium is
99.83%.
Embodiment three:
This includes the following steps from the method that Mycophenolic Acid bacterial strain preparation wheat examines phenol sodium.
Step (1) takes Mycophenolic Acid producing strains spore suspension, is inoculated on culture medium, cultivates 4 days at 28 DEG C；The seed
Each group in culture medium is divided into (unit: g/L) soybean cake powder 15, lactose 60, Dried Corn Steep Liquor Powder 40, ammonium nitrate 3, potassium dihydrogen phosphate
3, calcium carbonate 3, surplus is water.
Step (2), seed culture medium are inoculated in fermentor and add fermentation medium, and 28 DEG C are cultivated 11 days.Fermentation training
The each group supported in base is divided into (unit: g/L): soybean cake powder 25, cornstarch 15, glucose 65, fructose 90, Dried Corn Steep Liquor Powder
55, calcium carbonate 3, methionine 4, potassium dihydrogen phosphate 1.5, surplus is water.It carries out putting tank after fermentation to extract fermentation liquid.
Step (3), into fermentation liquid, addition acid makes fermentation liquid be acidified to pH in 4.0, and hydrogen-oxygen is then added into fermentation liquid
Changing sodium solution makes the pH of fermentation liquid in 8.5.Plate-frame filtering, filtrate are adjusted to pH in 2.5 with acid again, and it is thick to obtain Mycophenolic Acid for filtering
Product；Mycophenolic Acid crude product is dissolved in alcohols solvent rear decoloring, obtains Mycophenolic Acid after recrystallization.In the present embodiment, acid used
The dilute hydrochloric acid for being 10wt% for mass concentration.
Step (4), obtained Mycophenolic Acid and sodium methoxide carry out synthetic reaction in methanol, examine phenol sodium to generate wheat, instead
Answer temperature 60 C, the reaction time 3 hours.
The resulting reaction solution of step (4) is concentrated step (5), and crystallization is dry to examine phenol sodium to get whole product wheat.Crystallization mode
For 10 DEG C of crystallisation by cooling.Vacuum drying temperature is 50 DEG C, and vacuum drying vacuum degree is 0.5MPa.
For solid obtained by the present embodiment (i.e. " wheat examines phenol sodium ") through Physico-chemical tests, fusing point meets pertinent literature regulation 189
~191 DEG C, fusing point is 190.3~190.9 DEG C, is detected through HPLC, the purity that the wheat as made from this method examines phenol sodium is
99.85%.
Example IV:
This includes the following steps from the method that Mycophenolic Acid bacterial strain preparation wheat examines phenol sodium.
Step (1) takes Mycophenolic Acid producing strains spore suspension, is inoculated on culture medium, cultivates 3 days at 26 DEG C.Seed training
The each group supported in base is divided into (unit: g/L): soybean cake powder 10, lactose 50, Dried Corn Steep Liquor Powder 25, ammonium nitrate 2, potassium dihydrogen phosphate
2, calcium carbonate 2, surplus is water.
Step (2), seed culture medium are inoculated in fermentor and add fermentation medium, and 26 DEG C are cultivated 9 days.Fermentation medium
In each group be divided into (unit: g/L): soybean cake powder 20, cornstarch 10, glucose 50, fructose 80, corn pulp 50, calcium carbonate
1, methionine 3, potassium dihydrogen phosphate 0.5, surplus is water.It carries out putting tank after fermentation to extract fermentation liquid.
Step (3), into fermentation liquid, addition acid makes fermentation liquid be acidified to pH in 3.0, and hydrogen-oxygen is then added into fermentation liquid
Changing sodium solution makes the pH of fermentation liquid in 9.Plate-frame filtering, filtrate are adjusted to pH in 2.0 with acid again, and filtering obtains Mycophenolic Acid crude product；
Mycophenolic Acid crude product is dissolved in alcohols solvent rear decoloring, obtains Mycophenolic Acid after recrystallization.In the present embodiment, acid used is matter
Measure the dilute hydrochloric acid that concentration is 8wt%.
Mycophenolic Acid and sodium methoxide are carried out synthetic reaction by step (4) in ethanol, examine phenol sodium, reaction temperature to generate wheat
40 DEG C, the reaction time 3 hours of degree.
The resulting reaction solution of step (4) is concentrated step (5), crystallizes, dry.Crystallization mode is 60 DEG C of condensing crystallizings.Very
The dry temperature of sky is 50 DEG C, and vacuum drying vacuum degree is 0.2MPa.
For solid obtained by the present embodiment (i.e. " wheat examines phenol sodium ") through Physico-chemical tests, fusing point meets pertinent literature regulation 189
~191 DEG C, fusing point is 190.2~190.9 DEG C, is detected through HPLC, the purity that the wheat as made from this method examines phenol sodium is
99.89%.
Embodiment five:
This includes the following steps from the method that Mycophenolic Acid bacterial strain preparation wheat examines phenol sodium.
Step (1) takes Mycophenolic Acid producing strains spore suspension, is inoculated on culture medium, cultivates 3 days at 26 DEG C.Seed training
The each group supported in base is divided into (unit: g/L): soybean cake powder 10, lactose 50, Dried Corn Steep Liquor Powder 25, ammonium nitrate 2, potassium dihydrogen phosphate
2, calcium carbonate 2, surplus is water.
Step (2), seed culture medium are inoculated in fermentor and add fermentation medium, and 26 DEG C are cultivated 9 days；Fermentation medium
In each group be divided into (unit: g/L): soybean cake powder 20, cornstarch 10, glucose 50, fructose 80, Dried Corn Steep Liquor Powder 50, carbon
Sour calcium 1, methionine 3, potassium dihydrogen phosphate 0.5, surplus are water.It carries out putting tank after fermentation to extract fermentation liquid.
Step (3), into fermentation liquid, addition acid makes fermentation liquid be acidified to pH in 4.0, and hydrogen-oxygen is then added into fermentation liquid
Changing sodium solution makes the pH of fermentation liquid in 8.8.Plate-frame filtering, filtrate are adjusted to pH in 2.2 with acid again, and it is thick to obtain Mycophenolic Acid for filtering
Product；Mycophenolic Acid crude product is dissolved in alcohols solvent rear decoloring, obtains Mycophenolic Acid after recrystallization.In the present embodiment, acid used
The dilute sulfuric acid for being 5wt% for mass concentration.
Mycophenolic Acid and sodium hydroxide are carried out synthetic reaction by step (4) in normal propyl alcohol, examine phenol sodium to generate wheat.Instead
Answer 40 DEG C of temperature, the reaction time 3 hours.
The resulting reaction solution of step (4) is concentrated step (5), and crystallization is dry to examine phenol sodium to get whole product wheat.Crystallization mode
For 40 DEG C of condensing crystallizings.Vacuum drying temperature is 45 DEG C, and vacuum drying vacuum degree is -0.15MPa.
For solid obtained by the present embodiment (i.e. " wheat examines phenol sodium ") through Physico-chemical tests, fusing point meets pertinent literature regulation 189
~191 DEG C, fusing point is 189.7~190.3 DEG C, is detected through HPLC, the purity that the wheat as made from this method examines phenol sodium is
99.88%.
Embodiment six:
This includes the following steps from the method that Mycophenolic Acid bacterial strain preparation wheat examines phenol sodium.
Step (1) takes Mycophenolic Acid producing strains spore suspension, is inoculated on culture medium, cultivates 4 days at 28 DEG C；Seed training
It supports base component (g/L): soybean cake powder 15, lactose 60, Dried Corn Steep Liquor Powder 40, ammonium nitrate 3, potassium dihydrogen phosphate 3, calcium carbonate 3.
Step (2), seed culture medium are inoculated in fermentor and add fermentation medium, and 28 DEG C are cultivated 11 days.Fermented and cultured
Each group in base is divided into (unit: g/L): soybean cake powder 25, cornstarch 15, glucose 65, fructose 90, Dried Corn Steep Liquor Powder 55,
Calcium carbonate 3, methionine 4, potassium dihydrogen phosphate 1.5, surplus are water.It carries out putting tank after fermentation to extract fermentation liquid.
Step (3), into fermentation liquid, addition acid makes fermentation liquid be acidified to pH in 2.1, and hydrogen-oxygen is then added into fermentation liquid
Changing sodium solution makes the pH of fermentation liquid in 8.7.Plate-frame filtering, filtrate are adjusted to pH in 2.6 with acid again, and it is thick to obtain Mycophenolic Acid for filtering
Product；Mycophenolic Acid crude product is dissolved in alcohols solvent rear decoloring, obtains Mycophenolic Acid after recrystallization.In the present embodiment, acid used
The dilute hydrochloric acid for being 5wt% for mass concentration.
Mycophenolic Acid and sodium methoxide are carried out synthetic reaction by step (4) in n-butanol, examine phenol sodium to generate wheat.Reaction
Temperature 60 C, the reaction time 3 hours.
Step (5), by step (4) reaction solution be concentrated, crystallize, it is dry.Crystallization mode is 10 DEG C of crystallisation by cooling.Vacuum
Dry temperature is 42 DEG C, and vacuum drying vacuum degree is 0.32MPa.
For solid obtained by the present embodiment (i.e. " wheat examines phenol sodium ") through Physico-chemical tests, fusing point meets pertinent literature regulation 189
~191 DEG C, fusing point is 190.2~190.8 DEG C, is detected through HPLC, the purity that the wheat as made from this method examines phenol sodium is
99.86%.
The series of detailed descriptions listed above only for feasible embodiment of the invention specifically
Protection scope bright, that they are not intended to limit the invention, it is all without departing from equivalent implementations made by technical spirit of the present invention
Or change should all be included in the protection scope of the present invention.
It is obvious to a person skilled in the art that invention is not limited to the details of the above exemplary embodiments, Er Qie
In the case where without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, the present embodiments are to be considered as illustrative and not restrictive, and the scope of the present invention is by appended power
Benefit requires rather than above description limits, it is intended that all by what is fallen within the meaning and scope of the equivalent elements of the claims
Variation is included within the present invention.
In addition, it should be understood that although this specification is described in terms of embodiments, but not each embodiment is only wrapped
Containing an independent technical solution, this description of the specification is merely for the sake of clarity, and those skilled in the art should
It considers the specification as a whole, the technical solutions in the various embodiments may also be suitably combined, forms those skilled in the art
The other embodiments being understood that.
Claims (7)
1. the method for examining phenol sodium from Mycophenolic Acid bacterial strain preparation wheat, which comprises the following steps:
Step (1) takes Mycophenolic Acid bacterial strain producing strains spore suspension, is inoculated on seed culture medium and cultivates at 26~28 DEG C
2~4 days；
Step (2), seed culture medium are inoculated in fermentor and add fermentation medium, ferment 9~11 days at 26~28 DEG C, send out
It carries out putting tank to extract fermentation liquid after the completion of ferment；
Step (3) adds the sour pH for making fermentation liquid into fermentation liquid in 3~4, and sodium hydroxide solution is then added into fermentation liquid
Make the pH of fermentation liquid in 8~9, plate-frame filtering, filtrate is adjusted to pH in 2~3 with acid again, and filtering obtains Mycophenolic Acid crude product, by wheat
It examines phenolic acid crude product and is dissolved in alcohols solvent rear decoloring, obtain Mycophenolic Acid after recrystallization；
Mycophenolic Acid and sodium hydroxide or sodium methoxide are synthesized in alcohols solvent wheat and examine phenol sodium by step (4), wherein reaction temperature
Degree is 40~60 DEG C, the reaction time 1~3 hour；
Step (5) crystallizes after the reaction solution that step (4) obtains is concentrated, and filters, dry.
2. according to the method described in claim 1, the composition of the seed culture medium in the step (1) are as follows: soybean cake powder 5~
15g/L, 40~60g/L of lactose, 20~40g/L of Dried Corn Steep Liquor Powder, 1~3g/L of ammonium nitrate, 1~3g/L of potassium dihydrogen phosphate, carbonic acid
1~3g/L of calcium.
3. according to the method described in claim 1, the composition of the fermentation medium in the step (2) are as follows: soybean cake powder 15~
25g/L, 5~15g/L of cornstarch, 45~65g/L of glucose, 70~90g/L of fructose, 45~55g/L of Dried Corn Steep Liquor Powder, carbonic acid
1~3g/L of calcium, 2~4g/L of methionine, 0.5~1.5g/L of potassium dihydrogen phosphate.
4. concentration is 6~12mol/ according to the method described in claim 1, the acid in the step (3) is selected from hydrochloric acid or sulfuric acid
L, the alcohols solvent in the step (3) are selected from ethyl alcohol or methanol.
5. according to the method described in claim 1, alcohols solvent in the step (4) is selected from methanol, ethyl alcohol, normal propyl alcohol or just
Butanol.
6. according to the method described in claim 1, the crystallization mode in the step (5) is condensing crystallizing or crystallisation by cooling；Its
In, the temperature of condensing crystallizing is 40~60 DEG C, and the temperature of crystallisation by cooling is 0~10 DEG C.
7. according to the method described in claim 1, the drying mode in the step (5) is vacuum drying, vacuum drying temperature
Degree is 40~50 DEG C, and vacuum drying vacuum degree is 0.1~0.5MPa.
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| CN106866594A (en) * | 2017-02-17 | 2017-06-20 | 上海华源医药科技发展有限公司 | The optimize technique of phenol sodium industrialized production is examined suitable for wheat |
| CN112645912B (en) * | 2020-12-27 | 2022-05-13 | 广东蓝宝制药有限公司 | Preparation method of high-purity M2 crystal form meclofenol sodium |
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| CN101014584A (en) * | 2004-07-20 | 2007-08-08 | 特瓦药厂私人有限公司 | Crystalline mycophenolate sodium |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101014584A (en) * | 2004-07-20 | 2007-08-08 | 特瓦药厂私人有限公司 | Crystalline mycophenolate sodium |
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| "麦考酚酸产生菌液体发酵条件的优化";高兴蓉等;《中国医药工业杂志》;20070410;第38卷(第4期);第274页 |
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