CN106853295A - One kind is based on the scattered method for crystallising of film - Google Patents
One kind is based on the scattered method for crystallising of film Download PDFInfo
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- CN106853295A CN106853295A CN201510907289.XA CN201510907289A CN106853295A CN 106853295 A CN106853295 A CN 106853295A CN 201510907289 A CN201510907289 A CN 201510907289A CN 106853295 A CN106853295 A CN 106853295A
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- membrane
- crystallized
- crystallising
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D9/00—Crystallisation
Abstract
The scattered method for crystallising of film is based on the invention provides one kind, dispersant is evenly dispersed into the solution containing material to be crystallized by the scattered method of film, make material to be crystallized solubility reduction in the solution, so as to crystallize out.The membrane material can be reverse osmosis membrane, NF membrane, milipore filter, ceramic membrane, porous metal film etc..The method for crystallising can obtain crystal formation more preferably, and segregative crystal improves crystal product quality；The product larger to molecular weight may also function as improving the effect of crystallization operation speed.
Description
Technical field
The present invention relates to crystallization technique, can be used for chemical industry, pharmacy etc. needs to obtain the field of product using method for crystallising,
The scattered method for crystallising of film is based in particular to one kind.
Background technology
Crystallization technique is the conventional method for obtaining solid product of chemical industry, medicine and other fields, and usual crystallization process can go
The removal of impurity, improve product quality.
Method for crystallising has many kinds and continues to bring out out new crystalline technology and new technology.Following two methods are crystallization techniques
Through frequently with method：
One is that the material for needing crystallization is dissolved in a kind of solvent (hereinafter referred to as solvent one), adds another solvent
(hereinafter referred to as solvent two, in the present invention also referred to as dispersant), makes the material that needs are crystallized in the mixed of two kinds of solvents
Solubility is gradually reduced during conjunction, separates out crystal.Solvent one and solvent two can be water, organic solvent, some products
Product use water with the mixture of organic solvent or the mixture of organic solvent as solvent one, by different solvents to difference
The different principle of impurity solvability, reaches the purpose for removing different type impurity simultaneously.
Two is that the material that will need crystallization is dissolved in the mixed solution of water or water with organic solvent, adds acid, alkali, salt
The aqueous solution, reaching to reduce by the pH value or salinity that adjust crystallizing system needs the purpose of crystalline material solubility,
So as to obtain crystal.
Both method for crystallising identical places are to need to add dispersant molten toward the crystallizing system of the dissolving of solvent one
Agent two reduces whole system to needing the solubility of crystalline material, in most cases, can obtain good crystal.
But it is being difficult to obtain good crystal in some cases using the method, is causing follow-up separation of solid and liquid difficult, product quality
Decline, crystal cannot be even obtained sometimes causes crystallization to fail.Cause crystallization difficult or be the reason for failure, addition
During dispersant, because dispersant is very low to the Solubility of Substances for needing crystallization, the part that dispersant is contacted with crystallization solution
Region needs the Solubility of Substances of crystallization drastically to decline, and precipitates rather than crystallizing out rapidly, wherein wrapping up a large amount of impurity.
On the other hand, some impurities exhibits are smaller with the Solubility of Substances gap for needing to crystallize, also molten with crystallization in dispersant
The regional area of liquid contact precipitates pollution finished product.
In order to solve the problem, a kind of method being commonly used is to reduce the speed for adding dispersant, makes what is be precipitated out
Crystalline material or impurity slow mechanism dissolved again are needed, then makes to need crystalline material slowly to be given birth in the plane of crystal for producing before this
It is long, but the method causes crystallization time significantly to extend, and the slow-growing product of partial crystals wants a couple of days even longer
Time can just can be easily separated, up-to-standard product.Another method be by the way of similar shower nozzle,
Dispersant is dispersed into droplet as far as possible when adding dispersant, the region that making local solubility quickly reduces reduces, but
This method effect is limited.
The content of the invention
To solve above-mentioned problems of the prior art, the present invention proposes a kind of side of utilization membrane technology dispersed crystalline
Method.
Technical scheme is as follows：
A kind of method for crystallising, is to add dispersant in the solution containing material to be crystallized, makes material to be crystallized in solution
In solubility reduction, so as to crystallize out, it is characterised in that the dispersant by the scattered method of film equably
It is distributed in the solution containing material to be crystallized.
The scattered method of film is equably to pass through dispersant using the permeability of membrane material.Dispersant can pass through institute
State membrane material, but material to be crystallized molecule can not or denier pass through the membrane material.According to material to be crystallized and point
The characteristic of powder, selects specific membrane material, selectable membrane material include but is not limited to reverse osmosis membrane, NF membrane,
Milipore filter, ceramic membrane, porous metal film etc..
The material of needs crystallization is dissolved in water, organic solvent, water and organic solvent mixed solution or various organic solvents are mixed
Close in solution, as contain the solution of material to be crystallized.
The dispersant is typically the poor solvent of material to be crystallized, can be organic solvent, or water or water
Acid, alkali, salting liquid, due to the obvious principle of this method, however not excluded that ORGANIC SOLVENT MIXTURES, water-organic solvent
Solution, and organic solution and water and acid, alkali, the mixture of salt, suitable for method for crystallising of the present invention.
When above-mentioned method for crystallising is implemented, the present invention is devised crystallisation vessel, dispersion agent container and membrane material group
Device altogether, crystallisation vessel and dispersion agent container is separated with membrane material, the solution containing material to be crystallized
It is placed in crystallisation vessel, storage or dropwise addition dispersant in agent container is disperseed, dispersant uniformly enter knot through membrane material
In brilliant container.
Present invention also offers a kind of crystallization apparatus, including crystallisation vessel, dispersion agent container and membrane material, the crystallization
Container and dispersion agent container are separated by membrane material, and the edge of membrane material is sealed with two container junctions with encapsulant.
Membrane material described in above-mentioned crystallization apparatus can be reverse osmosis membrane, NF membrane, milipore filter, ceramic membrane or porous gold
Category film etc..
Preferably, the crystallisation vessel and dispersion agent container carry agitator.
Membrane technology is at present that, in the new technology that the fields such as chemical industry, medicine, environmental protection are widely used, its core material is can
So that by the membrane material of different size molecule, the material commonly used at present has reverse osmosis membrane, NF membrane, milipore filter, ceramics
Film, porous metal film etc..Film method is applied to crystallization technique by the present invention, achieves very big achievement.Membrane material
Bore dia below micron, even up to below nanometer, and every square millimeter be dispersed with it is up to tens thousand of, hundreds thousand of very
To more through-hole, relative to existing shower nozzle dispersing mode, the inventive method can obtain by a larger margin point
Dissipate, and smaller local low solubility region.The present invention adds dispersant to be crystallized using film method, can obtain
To crystal formation more preferably and can be easily separated crystal, improve crystal product quality, the product larger to molecular weight may also function as carrying
The effect of highly crystalline service speed.
Brief description of the drawings
Fig. 1 is the structural representation of the crystallization apparatus used by the embodiment of the present invention, wherein：1- crystallisation vessels, 2- dispersion agent containers,
3- membrane materials.
Specific embodiment
Below by way of the description of specific embodiment, the invention will be further described, but this is not to limit of the invention
System, those skilled in the art's basic thought of the invention, various modifications may be made or improves, but as long as not
Depart from basic thought of the invention, within the scope of the present invention.
The present invention crystallize the trial of technological change, and membrane material is introduced in the crystallization experiment for adding dispersant,
Verified by many experiments and found, dispersant is added by the scattered mode of film, can obtain crystal formation more preferably, can be easily separated
Crystal, improve crystal product quality effect, macromolecular product crystallization can also improve crystallization rate.Wherein, film
Material has attempted reverse osmosis membrane, NF membrane, milipore filter, ceramic membrane, porous metal film, the solvent that crystallization process is attempted
One mixed solution for having water, ethanol and acetone and water, the solvent two (i.e. dispersant) that crystallization process is attempted has water, second
Alcohol, acetum, ammonia spirit, sodium-chloride water solution.
Method for crystallising of the invention can not be passed through or few through the material for needing crystallization for membrane material requirement used
Molecule, but dispersant molecule can be passed through.
The method of dispersant can have：Directly dispersant is stored in dispersion agent container, crystallization is progressively distributed to
In container；A small amount of solvent one is first added in dispersion cup, dispersant is slowly added to wherein, in our experiment,
The product crystal formation and quality that second method is obtained are more preferable than first method.
In the present invention, the experiment that all of membrane material is carried out can obtain crystalline substance more more preferable than conventional dispersant feed postition
Type and more preferable product quality, but help less even reduce to improving service speed through the less membrane material of molecular weight
Service speed, and can pass through the bigger film of molecule can more improve service speed.
Present invention is further explained and described below by way of example, but these examples are understood not to the present invention
The limitation of protection domain.
To carry out the experiment, we have made crystallizer as shown in Figure 1：Dispersion cup and band including band stirring
Crystallisation vessel two parts of stirring, are separated between them by membrane material, and with encapsulant by membrane material edge and two
Container is tightly connected.
Embodiment 1
Certain fat-soluble antibiotic production crystal solution is taken, its solvent is ethanol and acetone and the mixed solution of water.Need to add
Dispersant be water, use conventional dropwise addition mode to crystallize be No. 1 experiment；In adding water to dispersion cup, by reverse osmosis
Permeable membrane is crystallized as No. 2 experiments in being diffused into crystallisation vessel.It was found that conventional knot during many experiments
Crystal type is most fast can about to obtain separable crystal in 5 hours, and due to the antibiotic molecule only has reverse osmosis membrane can
To stop, and water is too low through the speed of reverse osmosis membrane, and No. 2 experiments need to complete for about 11.5 hours.Therefore I
No. 1 experiment is divided into 2 groups, numbering is 1-1,1-2 respectively, and the time for adding of equal control water is small for 5,11.5
When, the finished product that obtains is separated, dry after detect purity.To judge separating difficulty, we are filtered and are washed with crystal
The time that suction filtration to 1 minute no liquid is dripped afterwards is used as the standard for judging to separate difficulty or ease.The experiment whole result such as institute of table 1
Show：
Table 1
| Experiment numbers | Crystallization time | Crystal separates situation | Finished product detection purity |
| 1-1 | 5 hours | Suction filtration 10 hour 57 minutes | 93.87% |
| 1-2 | 11.5 hours | Suction filtration 3 hour 21 minutes | 95.79% |
| No. 2 | 11.5 hours | Suction filtration 13 minutes | 97.22% |
Experiment can be seen that the reverse osmosis membrane dispersed crystalline mode that uses more than, and crystal separating difficulty reduction, product quality is improved,
But the crystallization operation time is without advantage.
Embodiment 2
Certain water soluble antibiotics production crystal solution is taken, its solvent is water.It is 95% ethanol to need the dispersant for adding,
It is No. 1 experiment to use conventional dropwise addition mode to crystallize；Directly by 95% ethanol addition dispersion cup, expanded by NF membrane
It is scattered to be tested as No. 2 in crystallisation vessel；A small amount of water is first added in dispersion cup, then 95% ethanol is added dropwise thereto
As No. 3 experiments.The membrane material for using is the NF membrane of nominal 350~450D.No. 2 and No. 3 experiments are carried out respectively
About 4.5 hours and 6.5 hours, No. 1 experiment can most obtain time about 4.5 hours of separable crystal, therefore I soon
No. 1 experiment is divided into 2 groups, numbering is 1-1,1-2 respectively, the ethanol time for adding of equal control 95% 4.5,
6.5 hours, the finished product that obtains is separated, dry after detect purity.Experiment whole result is as shown in table 2：
Table 2
| Experiment numbers | Crystallization time | Crystal separates situation | Finished product detection purity |
| 1-1 | 4.5 hours | Suction filtration 5 hour 46 minutes | 97.87% |
| 1-2 | 6.5 hours | Suction filtration 2 hour 37 minutes | 97.99% |
| No. 2 | 4.5 hours | Suction filtration 11 minutes | 98.43% |
| No. 3 | 6.5 hours | Suction filtration 9 minutes | 98.72% |
Experiment can be seen that the NF membrane dispersed crystalline mode that uses more than, and crystal separating difficulty reduction, product quality is improved,
The crystallization operation time is without clear superiority.
Embodiment 3
Certain macromolecular water soluble antibiotics production crystal solution is taken, its solvent is water, pH5.5.Need the dispersant for adding
For 2% ammonia spirit, it is necessary to by terminal pH controls 7.5.It is No. 1 experiment to use conventional dropwise addition mode to crystallize；Directly
It is connected in dispersion cup and adds 2% ammoniacal liquor as No. 2 experiments；A small amount of water is first added in dispersion cup, then thereto
2% ammoniacal liquor is added dropwise as No. 3 experiments.The membrane material for using is the milipore filter of nominal 1000D.No. 2 and No. 3 experiments
Carry out respectively 45 minutes about 2 hours and 15 minutes 4 hours, No. 1 experiment most obtains the time of separable crystal soon
About 5 hours.The finished product that obtains is separated, dry after detect purity.Experiment whole result is as shown in table 3：
Table 3
| Experiment numbers | Crystallization time | Crystal separates situation | Finished product detection purity |
| No. 1 | 5 hours | Suction filtration 7 hour 35 minutes | 93.25% |
| No. 2 | 45 minutes 2 hours | Suction filtration 19 minutes | 95.88% |
| No. 3 | 15 minutes 4 hours | Suction filtration 14 minutes | 96.24% |
Experiment can be seen that the milipore filter dispersed crystalline mode that uses more than, and crystal separating difficulty reduction, product quality is improved,
The crystallization operation time has shortened.
Embodiment 4
When the proteinaceous impurities that certain antibiotic fermentation is produced are separated, crystallization of protein liquid is obtained, its solvent is water,
pH6.0.It is 30% ammonium sulfate to need the dispersant for adding.It is No. 1 experiment to use conventional dropwise addition mode to crystallize；
30% ammonium sulfate is directly added in dispersion cup as No. 2 experiments；A small amount of water is first added in dispersion cup,
30% ammonium sulfate is added dropwise thereto again as No. 3 experiments.The membrane material for using is the flaky pottery of nominal 20nm
Film.No. 2 and No. 3 experiments have been carried out 25 minutes about 1 hour and 10 minutes 2 hours respectively, and No. 1 experiment most soon may be used
Obtain the about 6.5 hours time of separable crystal.The finished product that obtains is separated, dry after detect protein content.Experiment
Whole result is as shown in table 4：
Table 4
| Experiment numbers | Crystallization time | Crystal separates situation | Detection protein content |
| No. 1 | 6.5 hours | Suction filtration 11 hours | 25.73% |
| No. 2 | 25 minutes 1 hour | Suction filtration 35 minutes | 40.77% |
| No. 3 | 10 minutes 2 hours | Suction filtration 27 minutes | 50.92% |
Experiment can be seen that the ceramic membrane dispersed crystalline mode that uses more than, and crystal separating difficulty reduction, product quality is improved,
The crystallization operation time is greatly shortened.
Embodiment 5
With embodiment 4, when proteinaceous impurities separation is carried out, crystallization of protein liquid is obtained, its solvent is water, pH9.0.
It is 5% acetum to need the dispersant for adding, and final pH is reached 6.0.It is 1 to use conventional dropwise addition mode to crystallize
Number experiment；5% acetum is directly added in dispersion cup as No. 2 experiments；First added in dispersion cup few
Amount water, then 5% acetum is added dropwise thereto as No. 3 experiments.The membrane material for using is the porous of nominal 20nm
Titanium metal film.No. 2 and No. 3 experiments have been carried out 20 minutes about 1 hour and 15 minutes 2 hours respectively, No. 1 experiment
The about 7 hours time of separable crystal can be most obtained soon.The finished product that obtains is separated, dry after detect protein content.
Experiment whole result is as shown in table 5：
Table 5
| Experiment numbers | Crystallization time | Crystal separates situation | Detection protein content |
| No. 1 | 7 hours | Suction filtration 10 hour 35 minutes | 26.28% |
| No. 2 | 20 minutes 1 hour | Suction filtration 32 minutes | 41.53% |
| No. 3 | 15 minutes 2 hours | Suction filtration 24 minutes | 51.90% |
The experiment more than is as can be seen that use porous metal film dispersed crystalline mode, crystal separating difficulty reduction, product quality is carried
Height, the crystallization operation time is greatly shortened.
Claims (10)
1. a kind of method for crystallising, dispersant is added in the solution containing material to be crystallized, makes material to be crystallized molten
Solubility reduction in liquid, so as to crystallize out, it is characterised in that the dispersant is uniform by the scattered method of film
Be distributed in the solution containing material to be crystallized.
2. method for crystallising as claimed in claim 1, it is characterised in that the scattered method of film is to utilize membrane material
The permeability of material equably passes through dispersant.
3. method for crystallising as claimed in claim 2, it is characterised in that the membrane material is reverse osmosis membrane, nanofiltration
Film, milipore filter, ceramic membrane or porous metal film.
4. method for crystallising as claimed in claim 2, it is characterised in that the molecule of material to be crystallized can not or pole
It is micro to pass through the membrane material.
5. method for crystallising as claimed in claim 1, it is characterised in that the solution containing material to be crystallized is
Refer to that need the material of crystallization to be dissolved in water, organic solvent, water mixes with organic solvent mixed solution or various organic solvents
The solution that solution is formed.
6. method for crystallising as claimed in claim 1, it is characterised in that the dispersant be material to be crystallized not
Good solvent.
7. the method for crystallising as described in claim 1~6 is any, it is characterised in that using membrane material by crystallisation vessel
It is separated with dispersion agent container, the solution containing material to be crystallized is placed in crystallisation vessel, then in dispersion
Dispersant is stored or is added dropwise in agent container, and dispersant uniformly enters in crystallisation vessel through membrane material, makes material to be crystallized
Crystallize out.
8. a kind of crystallization apparatus, including crystallisation vessel, dispersion agent container and membrane material, the crystallisation vessel and dispersion
Agent container is separated by membrane material, and the edge of membrane material is sealed with two container junctions with encapsulant.
9. crystallization apparatus as claimed in claim 8, it is characterised in that the membrane material is reverse osmosis membrane, nanofiltration
Film, milipore filter, ceramic membrane or porous metal film.
10. crystallization apparatus as claimed in claim 8, it is characterised in that the crystallisation vessel and dispersion agent container are equal
With agitator.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1326803A (en) * | 2000-05-26 | 2001-12-19 | 辉瑞产品公司 | Reaction crystallizing method for improving grain size |
| US20060182808A1 (en) * | 2003-04-29 | 2006-08-17 | Akzo Nobel N.V. | Antisolvent solidification process |
| CN103648634A (en) * | 2011-07-13 | 2014-03-19 | M技术株式会社 | Method for manufacturing microparticles with regulated crystallite diameter |
| CN105031963A (en) * | 2015-07-08 | 2015-11-11 | 华南理工大学 | Crystallization method integrating anti-solvent crystallization, vacuum evaporation and cooling or anti-solvent crystallization |
-
2015
- 2015-12-09 CN CN201510907289.XA patent/CN106853295A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1326803A (en) * | 2000-05-26 | 2001-12-19 | 辉瑞产品公司 | Reaction crystallizing method for improving grain size |
| US20060182808A1 (en) * | 2003-04-29 | 2006-08-17 | Akzo Nobel N.V. | Antisolvent solidification process |
| CN103648634A (en) * | 2011-07-13 | 2014-03-19 | M技术株式会社 | Method for manufacturing microparticles with regulated crystallite diameter |
| CN105031963A (en) * | 2015-07-08 | 2015-11-11 | 华南理工大学 | Crystallization method integrating anti-solvent crystallization, vacuum evaporation and cooling or anti-solvent crystallization |
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Application publication date: 20170616 |
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