CN102399205A - Mycophenolic acid purification process - Google Patents
Mycophenolic acid purification process Download PDFInfo
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- CN102399205A CN102399205A CN2011104122023A CN201110412202A CN102399205A CN 102399205 A CN102399205 A CN 102399205A CN 2011104122023 A CN2011104122023 A CN 2011104122023A CN 201110412202 A CN201110412202 A CN 201110412202A CN 102399205 A CN102399205 A CN 102399205A
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Abstract
The invention relates to a mycophenolic acid purification process, which is applied to mycophenolic acid purification. The process comprises the following steps of: dissolving crude mycophenolic acid in methanol, decoloring, filtering by using a plate frame, concentrating, and crystallizing to obtain refined mycophenolic acid. The process is simple, easy to operate and suitable for industrial production.
Description
Technical field
The present invention relates to a kind of mycophenolic acid purifying process, be applied to the mycophenolic acid purifying.
Background technology
Mycophenolic acid has another name called Mycophenolic Acid; English name Mycophenolic Acid, chemical name: 6-(4-hydroxyl-6-methoxyl group-different band benzo of 7-methyl-3-oxo-5-mutter base)-4-methyl-4-is olefin(e) acid, molecular formula: C17H20O6; Molecular weight: 320.34; White or off-white color crystalline powder are soluble in methylene dichloride, trichloromethane; Be dissolved in acetone, acetate, ethyl ester; Slightly be dissolved in methyl alcohol, micro dissolution is in ethanol, and is almost insoluble in the water.Mycophenolic acid is a kind of low-molecular-weight bioactive compounds, to gram positive bacterium, dermatophytes and viral biologically active, and has the selectivity immunosuppressive action, and this mechanism is with mycophenolic acid Nucleotide synthetic selectivity to be suppressed relevant.Mycophenolic acid forms mycophenolate through esterification, is mainly used in kidney and other organs and transplants the anti-prevention of repelling.
It is less that present domestic mycophenolic acid extracts purifying research; At paper aspect the mycophenolic acid purifying " development of neotype immunosuppressant mycophenolic acid and mycophenlate mofetil " arranged; Wherein mention the ETHYLE ACETATE that the mycophenolic acid bullion is dissolved in fully 2 times of volumes, add 5% activated carbon decolorizing, the filtering gac; Destainer concentrates-4 ℃ and places 24h, separates out a large amount of light brown mycophenolic acid needle-like crystals; Be dissolved in bullion fully in 5 times of volume of ethanol at 40 ℃, place 24h for-4 ℃, filtration, drying have obtained content and have reached 99% the pure article of mycophenolic acid, and its purification yield is about 60%.It is consuming time oversize that this technology can not solve repeatedly the recrystallization method of purification, can't reduce defectives such as ETHYLE ACETATE, alcoholic acid waste.
Summary of the invention
In order to overcome the above problems, developed a kind of mycophenolic acid purifying process, the purpose of this invention is to provide the technology that a kind of mycophenolic acid purifying was not only simple but also be convenient to operate.
The present invention is dissolved in methyl alcohol with the bullion mycophenolic acid, through decolouring, Plate Filtration, concentrate, crystallization gets the mycophenolic acid elaboration, only needs a primary purification can reach purity more than 99%.The present invention has avoided repeatedly the recrystallization method of purification consuming time oversize, can't reduce defectives such as ETHYLE ACETATE, alcoholic acid waste, can reduce cost greatly again simultaneously.
The present invention provides a kind of mycophenolic acid purifying process, mainly handles through following operation:
1. mycophenolic acid dissolving crude product: press bullion weight and add the times solvent, hot water is heated to dissolving, stirs and guarantees that bullion dissolves fully, adds gac by a certain percentage and stirs, leaves standstill;
2. vertical Plate Filtration: the mycophenolic acid solvent solutions is crossed vertical sheet frame after pressurizeing, collect filtered liq;
3. vacuum rises membrane-concentrated: filtered liq is pumped into rise the film device and concentrate;
4. elaboration mycophenolic acid crystallization: the liquid concentrator cooling, leave standstill crystallization;
5. settling centrifuge separates: separate mother liquor and mycophenolic acid with settling centrifuge.
The present invention provides a kind of mycophenolic acid purifying process, and wherein to gather 1 indication solvent be methyl alcohol the step.
The present invention provides a kind of mycophenolic acid purifying process, and wherein going on foot the amount of gathering 1 indication adding gac is the 6%--10% of mycophenolic acid bullion quality.
The present invention provides a kind of mycophenolic acid purifying process, and wherein the step gathers 1 indication to add the solvent amount be 18-22 times of bullion weight.
The present invention provides a kind of mycophenolic acid purifying process, wherein the step gather be heated in 1 solvent temperature be 50-90 the degree.
The present invention provides a kind of mycophenolic acid purifying process, vertical Plate Filtration in the step 3 wherein, and used pressure is 0.3-0.8MPa, preferentially selects 0.4-0.6Mpa; The flow of mycophenolic acid solvent solutions in vertical Plate Filtration system is 10-50L/m2.h, preferentially selects 15-20L/m2.h.
The present invention provides a kind of mycophenolic acid purifying process, and wherein vacuum rises membrane-concentrated in the step 2, and the used film device flow that rises is 300-800 L/h, preferentially selects 500-600 L/h; Be concentrated to 30%-50% of original volume.
The present invention provides a kind of mycophenolic acid purifying process, and wherein the step gathers in 3 cooling temperature and is-5-0 degree.
The present invention provides a kind of mycophenolic acid purifying process, and wherein the step gathers that to leave standstill crystallization time in 3 be 10-15 hours.
The present invention provides a kind of mycophenolic acid purifying process, and wherein to gather 4 used settling centrifuge specifications be φ 600, rotating speed 1600rpm the step, and flow control 300-500 was Shenged ∕ hour.
Compare with existing Technology, the present invention has outstanding feature:
1, this technology has solved the repeatedly crystallization long problem that expends time in, and only needs primary crystallization can make the above mycophenolic acid of 99% purity, takes to be merely the half the of original process time;
2, this technology greatly reduces the waste of solvent, has reduced cost;
3, this technological operation is simple, and working condition is easy to realize control, helps suitability for industrialized production.
Embodiment
In order better to set forth a kind of mycophenolic acid purifying process proposed by the invention, adopt embodiment that the present invention is further specified below.
Embodiment 1
A certain amount of mycophenolic acid is added in the dissolving vessel, again in mycophenolic acid: the ratio of methyl alcohol=1:20 adds methyl alcohol, and control material system temperature is dissolving about 90 degree, treats that the mycophenolic acid dissolving finishes, and adds 6% gac stirring 30 minutes, immediately with hot soln with 17L/m
2.h through vertical Plate Filtration, the vacuum of will filtrating again rises 40% of membrane-concentrated to original volume, and the used film device flow that rises is 600 L/h;, again liquid concentrator is put in encloses container, under room temperature 30 degree, be cooled to 0 degree with frozen water; Left standstill 12 hours, and obtained purity and reach 99.3% mycophenolic acid.
Embodiment 2
A certain amount of mycophenolic acid is added in the dissolving vessel, again in mycophenolic acid: the ratio of methyl alcohol=1:19 adds methyl alcohol, and control material system temperature is dissolving about 70 degree, treats that the mycophenolic acid dissolving finishes, and adds 6% gac stirring 50 minutes, immediately with hot soln with 20L/m
2.h through vertical Plate Filtration, the vacuum of will filtrating again rises 40% of membrane-concentrated to original volume, and the used film device flow that rises is 550 L/h;, again liquid concentrator is put in encloses container, under room temperature 30 degree, be cooled to-4 degree with frozen water; Left standstill 10 hours, and obtained purity and reach 99.4% mycophenolic acid.
Embodiment 3
A certain amount of mycophenolic acid is added in the dissolving vessel, again in mycophenolic acid: the ratio of methyl alcohol=1:21 adds methyl alcohol, and control material system temperature is dissolving about 60 degree, treats that the mycophenolic acid dissolving finishes, and adds 8% gac stirring 40 minutes, immediately with hot soln with 20L/m
2.h through vertical Plate Filtration, the vacuum of will filtrating again rises 30% of membrane-concentrated to original volume, and the used film device flow that rises is 600 L/h;, again liquid concentrator is put in encloses container, under room temperature 30 degree, be cooled to-1 degree with frozen water; Left standstill 14 hours, and obtained purity and reach 99.6% mycophenolic acid.
Embodiment 4
A certain amount of mycophenolic acid is added in the dissolving vessel, again in mycophenolic acid: the ratio of methyl alcohol=1:18 adds methyl alcohol, and control material system temperature is dissolving about 80 degree, treats that the mycophenolic acid dissolving finishes, and adds 10% gac stirring 30 minutes, immediately with hot soln with 18L/m
2.h through vertical Plate Filtration, the vacuum of will filtrating again rises 35% of membrane-concentrated to original volume, and the used film device flow that rises is 500 L/h;, again liquid concentrator is put in encloses container, under room temperature 30 degree, be cooled to-3 degree with frozen water; Left standstill 15 hours, and obtained purity and reach 99.4% mycophenolic acid.
Claims (10)
1. a mycophenolic acid purifying process is dissolved in methyl alcohol with the bullion mycophenolic acid, through decolouring, Plate Filtration, concentrate, crystallization gets the mycophenolic acid elaboration, be primarily characterized in that:
A. mycophenolic acid dissolving crude product: press bullion weight and add the times solvent, hot water is heated to dissolving, stirs and guarantees that bullion dissolves fully, adds gac by a certain percentage and stirs;
B. vertical Plate Filtration: the mycophenolic acid solvent solutions is crossed vertical sheet frame after pressurizeing, collect filtered liq;
C. elaboration mycophenolic acid crystallization: the liquid concentrator cooling, leave standstill crystallization;
D. settling centrifuge separates: separate mother liquor and mycophenolic acid with settling centrifuge.
2. according to 1 one kinds of mycophenolic acid purifying process of claims, it is characterized in that the indication solvent is a methyl alcohol in the mycophenolic acid dissolving crude product.
3. according to 1 one kinds of mycophenolic acid purifying process of claims, it is characterized in that in the mycophenolic acid dissolving crude product adding the solvent amount and be 18-22 times of bullion weight.
4. the present invention provides a kind of mycophenolic acid purifying process, and wherein going on foot the amount of gathering 1 indication adding gac is the 6%--10% of mycophenolic acid bullion quality.
5. according to 1 one kinds of mycophenolic acid purifying process of claims, it is characterized in that being heated in the mycophenolic acid dissolving crude product solvent temperature is 50-90 degree.
6. according to 1 one kinds of mycophenolic acid purifying process of claims, its characteristic is at vertical Plate Filtration, and used pressure is 0.3-0.8MPa, preferentially selects 0.4-0.6Mpa; The flow of mycophenolic acid solvent solutions in vertical Plate Filtration system is 10-50L/m
2.h, preferentially select 15-20L/m
2.h.
7. according to 1 one kinds of mycophenolic acid purifying process of claims, its characteristic rises membrane-concentrated in vacuum, and the used film device flow that rises is 300-800 L/h, preferentially selects 500-600 L/h; Be concentrated to 30%-50% of original volume.
8. according to 1 one kinds of mycophenolic acid purifying process of claims, it is characterized in that elaboration mycophenolic acid crystallization cooling temperature is-5-0 degree.
9. according to 1 one kinds of mycophenolic acid purifying process of claims, it is characterized in that it is 10-15 hours that crystallization time is left standstill in the crystallization of elaboration mycophenolic acid.
10. according to 1 one kinds of mycophenolic acid purifying process of claims, it is characterized in that used settling centrifuge specification is φ 600, rotating speed 1600rpm, centrifugal flow control 300-500 rose ∕ hour.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011104122023A CN102399205A (en) | 2011-12-13 | 2011-12-13 | Mycophenolic acid purification process |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011104122023A CN102399205A (en) | 2011-12-13 | 2011-12-13 | Mycophenolic acid purification process |
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| CN102399205A true CN102399205A (en) | 2012-04-04 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103664848A (en) * | 2012-09-13 | 2014-03-26 | 北大方正集团有限公司 | Extracting method of mycophenolic acid |
| CN103880798A (en) * | 2012-12-19 | 2014-06-25 | 北大方正集团有限公司 | Mycophenolic acid purification method |
| CN107903228A (en) * | 2017-12-01 | 2018-04-13 | 焦作健康元生物制品有限公司 | A kind of high-purity mycophenolic acid production technology |
| CN108727317A (en) * | 2017-04-25 | 2018-11-02 | 鲁南制药集团股份有限公司 | A kind of crystal form object of Mycophenolic Acid |
| CN116041293A (en) * | 2023-02-08 | 2023-05-02 | 丽珠集团新北江制药股份有限公司 | Method for purifying mycophenolic acid |
-
2011
- 2011-12-13 CN CN2011104122023A patent/CN102399205A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| 高兴蓉: "新型免疫抑制剂酶酚酸及酶酚酸酯的研制", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103664848A (en) * | 2012-09-13 | 2014-03-26 | 北大方正集团有限公司 | Extracting method of mycophenolic acid |
| CN103664848B (en) * | 2012-09-13 | 2016-03-23 | 北大方正集团有限公司 | A kind of extracting method of mycophenolic acid |
| CN103880798A (en) * | 2012-12-19 | 2014-06-25 | 北大方正集团有限公司 | Mycophenolic acid purification method |
| CN103880798B (en) * | 2012-12-19 | 2016-04-20 | 北大方正集团有限公司 | A kind of method of purifying mycophenolic acid |
| CN108727317A (en) * | 2017-04-25 | 2018-11-02 | 鲁南制药集团股份有限公司 | A kind of crystal form object of Mycophenolic Acid |
| CN107903228A (en) * | 2017-12-01 | 2018-04-13 | 焦作健康元生物制品有限公司 | A kind of high-purity mycophenolic acid production technology |
| CN116041293A (en) * | 2023-02-08 | 2023-05-02 | 丽珠集团新北江制药股份有限公司 | Method for purifying mycophenolic acid |
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Application publication date: 20120404 |