CN100441285C - Hypergravity-supercritical reaction/crystallizing device and application/crystallizing technique - Google Patents
Hypergravity-supercritical reaction/crystallizing device and application/crystallizing technique Download PDFInfo
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Abstract
The present invention relates to a hypergravity supercritical reaction/crystallisation device which comprises a reaction chamber, a rotor, a magnetic force driver, an input pipe for supercritical fluid, at least one input pipe for materials, a filter core and a decompression port, wherein the reaction chamber is limited by a hermetical casing with pressure resistance; the rotor with a hollow circular cylinder is positioned in the reaction chamber, the inner wall and the outer wall of the circular cylinder are provided with small pores as liquid passages, and filling materials are filled between the inner wall and the outer wall of the circular cylinder; the magnetic force driver is fixed on the casing and is used for driving the rotation of the rotor by the connection of a shaft and the rotor; the input pipe is used for the supercritical fluid, and consequently, the supercritical fluid is sprayed to the inner wall of the circular cylinder of the rotor in the basically vertical direction; the input pipes are used for materials, and consequently, the materials are sprayed to the inner wall of the circular cylinder of the rotor in the basically vertical direction and are converged with the supercritical fluid; the filter core is arranged at the bottom of the reaction chamber; the decompression port is arranged on the casing to make the supercritical fluid gasified, and the liquid in the reaction chamber is carried away and exhausted by the filtration of the filter core; consequently, a dried product is obtained.
Description
Technical field
The present invention relates to a kind of reaction/crystallization apparatus, more particularly, relate to a kind of hypergravity-supercritical reaction/crystallization apparatus.The invention still further relates to the technology of in hypergravity-supercritical reaction/crystallization apparatus, carrying out chemical reaction/crystallization.
Background technology
In recent years, revolving bed (rotor) centrifugal force reinforcement transmission that produces and the technology of reacting had appearred utilizing.It has improved the area that contacts in the unit container, has greatly strengthened mass transfer intensity.This is breakthrough progress for traditional mass transfer technology.
People's such as James W.Wem U.S. Pat 4,382,900 discloses a kind of centrifugal gas-liquid contact apparatus.The disc-like rotor that is contained on the fixing casing is done rotation at a high speed, the ring packing layer is housed on the rotor, raw material liq enters from the center feed tube, stretch into the liquid distribution trough (that is: spray hole) of bed mid portion by feed tube lower end, center, spray to the inner ring surface of ring packing, in the ring packing, have gas on the outer ring surface, the liquid hole, it is airtight that other parts keep, and liquid enters filler from the hole of filler inner ring surface, under super gravity field, radially diffusion, the air inlet pipe of gas slave shell-side face enters, and under the effect of barometric gradient, enters filler by the ring packing outer ring surface, in filler, gas-liquid phase counter current contacting, behind the transfer reaction, gas is discharged by blast pipe, liquid is thrown out of filler, discharges from the discharging tube (13) of bottom of shell.This device is claimed the problem that the liquid of carrying secretly in the air-flow enters internal rotor that solved.
This device is the structure of single-phase cloth liquid.Can not satisfy multiphase flow, the reaction that particularly exists two kinds of different liquids raw materials to participate in.For this reason, people's such as Chen Jianfeng Chinese utility model patent 95215430.7 discloses a kind of rotating bed super gravity field device, in airtight casing, one rotor rotated is arranged, be fixed with the ring packing layer on the rotor, be furnished with liquid distribution trough in the packing layer annular space, liquid distribution trough and raw material feed tube join, it is characterized in that: be furnished with two groups of liquid distribution troughs in the packing layer annular space, the raw material feed tube is made up of interior pipe and outer tube, inside and outside sleeve pipe is connected with two groups of liquid distribution troughs respectively, and internal and external casing one end is respectively equipped with the raw material inlet.This device can carry out the reaction of liquid-liquid phase.A series of nano-powder materials have been obtained.Also referring to Chinese patent application: 95105343.3.
Along with further research in depth, the applicant finds, though high-gravity rotating bedly can provide Rapid and uniform microcosmic to mix, can control effectively to the reaction nucleation stage, if but rate of crystalline growth is slower, and the time of staying of material in revolving bed is shorter, causes in follow-up separation, dry run crystal still in growth, and this is unfavorable for preparing, and particle diameter is little, the product of narrow particle size distribution.This is because after said apparatus carries out reactive liquid solution, the product of separating out need be shifted out reactor, separates then, obtains final product through washing, drying.Because through these steps, the particle that the particle diameter that produces in the said apparatus is very little (primary diameter) is constantly grown up.With respect to primary diameter, the granularity of final product increases.Particularly, all the more so for macromolecular substances such as medicine or polymer substance.
At such situation, need seek to realize the apparatus and method that effectively to control nucleation and growth course.
Supercritical technology grew up in recent years, particularly adopted carbon dioxide as supercritical fluid media, and supercritical temperature is greatly reduced, and had improved the security reliability of equipment, made supercritical technology be transformed into possibility to the practicability direction.Supercritical fluid is that a kind of temperature and pressure is in the above no gas-liquid interface difference of critical point and has the material phase of liquid property and gas property concurrently, it has special solubility, the density of easy modulation, lower viscosity, demonstrate unique advantage and using value (mutually grand ZhongBing etc. as solvent and drying medium, Materials Science and Engineering, 1995,13 (2): 38-42).Chinese patent (ZL94193201.X) provides a kind of method that adopts supercritical technology to prepare the new naphthalene Fitow of the salmeterol that is easy to handle the crystal form that is easy to fluidisation (salmeterol xinafoate) of the size and dimension with control.In this patent, adopt coaxial nozzle, the dispersion of guaranteeing to deposit the carrier that contains valuable solid through the shear action of high speed supercritical fluid with special angle.In addition, compare with a conventional oven seasoning, adopt the methyl hydride combustion catalyst LaMnAl11O19 of supercritical drying drying method preparation can keep the aluminium dispersed uniform, make that the decomposition temperature of manganese carbonate and lanthanum carbonate obviously reduces in the complex catalyst precursor thing, and the dehydration temperaturre of aluminium hydroxide maintains in the suitable scope; After the roasting, easily form the hexa-aluminate phase.And catalytic activity is apparently higher than the catalyst that makes with a conventional oven drying means.(Xu Jinguang, Tian Zhijian etc., catalysis journal, 2002,23 (5): 477-480).But all the hypergravity rotation is combined crystallization and/or the reaction that is used for material with supercritical fluid technique in the prior art without any attempting.
Through deep research, the inventor finds to carry out the hypergravity reaction under the supercritical fluid effect, can obtain the material that particle diameter is littler, product purity is higher effectively.Based on this, the inventor has finished the present invention.
Therefore, one of purpose of the present invention provides a kind of new crystallization/reaction unit, and it can realize the effective control to nucleation and growth course.
Another object of the present invention provides a kind of new technology, and it can realize the effective control to nucleation and growth course.
Another purpose of the present invention is the above-mentioned application of device in purifying substances.
Summary of the invention
A kind of hypergravity-supercritical reaction/crystallization apparatus, it comprises:
The reative cell that limits by withstand voltage sealing shell;
Be positioned at the rotor with first hollow circular cylinder of reative cell, have aperture and/or groove on the first hollow circular cylinder inside and outside wall, fill filler between the first hollow circular cylinder inside and outside wall as fluid passage;
Be fixed on the shell, be connected with rotor to drive the magnetic driver of rotor rotation by axle;
The input pipe of shooting flow body and function, its end have one group of opening and extend into the hollow region of first hollow circular cylinder, thereby make supercritical fluid spray to the cylindrical inwall of rotor with the perpendicular direction;
At least one input pipe that material is used, its end has one group of opening and extends into the hollow region of first hollow circular cylinder, thereby makes material flow spray to the cylindrical inwall of rotor with the perpendicular direction and converge at inwall with supercritical fluid from the ejection of the input pipe of shooting flow body and function basically;
Be arranged on the filter core of reative cell bottom;
Be arranged on the relief port on the shell, make supercritical fluid gasification and through the filter core filter bag walk and/discharge the liquid in the reative cell, thereby obtain dry product.
The invention still further relates to the technology that adopts said apparatus to carry out chemical reaction/crystallization.
Description of drawings:
Fig. 1 is the schematic diagram of hypergravity-supercritical reaction of the present invention/a kind of embodiment of crystallization apparatus.
Fig. 2 is the structure chart of hypergravity-supercritical reaction of the present invention/crystallization apparatus rotor.
Fig. 3 is the another kind of structure chart of hypergravity-supercritical reaction of the present invention/crystallization apparatus rotor.
Fig. 4 is the structure chart of the filter core among Fig. 1 of the present invention.
Fig. 5 A-5D is the schematic cross-section of the relative position of supercritical fluid in hypergravity-supercritical reaction of the present invention/crystallization apparatus and material woven hose.
Fig. 6 is used for single flow chart of planting material for hypergravity-supercritical reaction of the present invention/crystallization apparatus.
Fig. 7 is used for the flow chart of two kinds/various materials for hypergravity-supercritical reaction of the present invention/crystallization apparatus.
Fig. 8 is a kind of preferred structure of magnetic drive unit in hypergravity-supercritical reaction of the present invention/crystallization apparatus.
Wherein Reference numeral is as follows:
20 turret head plug-in units, 21 upper bearing (metal)s, 22 outer magnets
24 times ball bearings of 23 inner magnets, 25 O-shapes ring
26 cooling agent refluxing openings 1/8 " NPT (F) 27 liners
Ball bearing on the 28 29 O-shape rings 30
31 bearing chambers, 32 intermediate bearings, 33 cooling agent supply ports 1/8 " NPT (F)
34 water collars, 35 lower bearings, 36 reactor caps
Fig. 9 is that the product pork insulin 1000 that the technology of employing hypergravity-supercritical reaction of the present invention/crystallization apparatus obtains shows little photo.
Figure 10 A-9,10B adopt 1000 of product bovine serum albumin that the technology of hypergravity-supercritical reaction of the present invention/crystallization apparatus obtains and bovine serum albumin raw material to show little photo.
Figure 11 is that the product papain 1000 that the technology of employing hypergravity-supercritical reaction of the present invention/crystallization apparatus obtains shows little photo.
Figure 12 A-9,12B adopt 1000 of product Cefradine that the technology of hypergravity-supercritical reaction of the present invention/crystallization apparatus obtains and Cefradine to show little photo.
Figure 13 A is that the concentration when Cefradine is 3%, and when system temperature was 35 ℃, pressure was to the influence of particle diameter.
The concentration that Figure 13 B works as Cefradine is 3%, 1.00MPa when system pressure is, and temperature is seen Figure 10 to the influence of particle diameter.
1.00MPa when Figure 13 C system pressure is, during 35 ℃ of temperature, the concentration of Cefradine is seen Figure 11 to the influence of particle diameter.
The specific embodiment
Term used herein " supercritical fluid " refers to the fluid that is in simultaneously or is higher than its critical pressure (Pc) and critical-temperature (Tc), and in fact, the pressure of fluid can be 1.01Pc～7.0Pc.Its temperature is 1.01Tc～4.0Tc.
The term of Shi Yonging " hypergravity " is meant the centrifugal force that is produced by the rotor rotation except that gravity in this article, and this centrifugal force is greater than gravity.
The term of Shi Yonging " high-gravity rotating bed " is meant and can rotates the equipment that produces centrifugal force in this article.It with " rotor " but trans-substitution mutually.
Term " entrainer " is that those of skill in the art are known in the prior art.Be also referred to as and guide and support agent, cosolvent, dressing agent or improver.Be a kind of a small amount of solvent that is added in the shooting flow system, its adding can change the phase behavior of shooting flow system significantly, particularly for the very little solute of solubility in supercritical fluid, may increase its solubility widely.
The invention provides a kind of hypergravity-supercritical reaction/crystallization apparatus, it comprises:
The reative cell that limits by withstand voltage sealing shell;
Be positioned at the rotor with first hollow circular cylinder of reative cell, have aperture and/or groove on the first hollow circular cylinder inside and outside wall, fill filler between the first hollow circular cylinder inside and outside wall as fluid passage;
Be fixed on the shell, be connected with rotor to drive the magnetic driver of rotor rotation by axle;
The input pipe of shooting flow body and function, its end have one group of opening and extend into the hollow region of first hollow circular cylinder, thereby make supercritical fluid spray to the cylindrical inwall of rotor with the perpendicular direction;
At least one input pipe that material is used, its end has one group of opening and extends into the hollow region of first hollow circular cylinder, thereby makes material flow spray to the cylindrical inwall of rotor with the perpendicular direction and converge at inwall with supercritical fluid from the ejection of the input pipe of shooting flow body and function basically;
Be arranged on the filter core of reative cell bottom;
Be arranged on the relief port on the shell, make supercritical fluid gasification and through the filter core filter bag walk and/discharge the liquid in the reative cell, thereby obtain dry product.
In reaction/crystallization apparatus of the present invention, described rotor also has and coaxial mounted second hollow circular cylinder of first hollow circular cylinder, the internal diameter of described second hollow circular cylinder is greater than the external diameter of first hollow circular cylinder, have aperture and/or groove on the described second hollow circular cylinder inside and outside wall as fluid passage, fill filler between the second hollow circular cylinder inside and outside wall.
In reaction/crystallization apparatus of the present invention, described rotor can also have and coaxial mounted the 3rd hollow circular cylinder of first and second hollow circular cylinders, the internal diameter of described the 3rd hollow circular cylinder is greater than the external diameter of second hollow circular cylinder, and have aperture and/or groove on described the 3rd hollow circular cylinder inside and outside wall as fluid passage, fill filler between the 3rd hollow circular cylinder inside and outside wall.According to actual needs, also can comprise the 4th, the 5th or the more and coaxial mounted hollow circular cylinder of first hollow circular cylinder.
Filler can be woven wire, foam metal, video disc, bead and spiral filling, wherein preferable alloy silk screen, the more preferably ripple silk net in the woven wire.The reaction that this depends in the device to be carried out.
The groove of opening at the inner surface of above-mentioned hollow circular cylinder can be helicla flute, thread groove, wave groove, circumferential slot and axial groove, and the combination of various forms fluting.
In the present invention, rotor is connected with the method for driving shaft with magnetic force.This magnetic connects can guarantee device sealing under high pressure.Driving shaft of the present invention can be a kind of magnetic driver, sees Fig. 8, can be from Reaction Engineering, and Inc. obtains with M-series.
In the present invention, for a kind of material, adopt a material input pipe.For two or more materials, can two or many material input pipes of corresponding employing.
In above-mentioned device, supercritical fluid can be carbon dioxide, ethane, ethene, propane, the third rare and freon-13 (CClF
3) etc., preferably carbon dioxide especially, and randomly have modifier or entrainer.
Filter core of the present invention can be multiple shape, and preferably a kind of reverse frustoconic can filter so most effectively.Filter core can be active carbon filter core, ceramic element, doughnut filter core, also can be the filter core that coats one or more layers membrane material, and membrane material comprises general membrane material, milipore filter material and NF membrane material.The object lesson of material for core comprises: poly tetrafluoroethylene (PTFE) filter core, PS membrane (HE) filter core, polypropylene screen (PP) filter core, nylon membrane (N66) filter core, cellulose acetate film (CA-CN) filter core, melt and spray film (PPC) filter core.It can obtain with 321000 models from Shuande city round trip flight filtering core device factory.
The present invention also provides a kind of and carry out chemical reaction/crystallization processes in hypergravity-shooting flow precursor reactant/crystallization apparatus, and this device comprises:
The reative cell that limits by withstand voltage sealing shell;
Be positioned at the rotor with first hollow circular cylinder of reative cell, have aperture and/or groove on the first hollow circular cylinder inside and outside wall, fill filler between the first hollow circular cylinder inside and outside wall as fluid passage;
Be fixed on the shell, be connected with rotor to drive the magnetic driver of rotor rotation by axle;
The input pipe of shooting flow body and function, its end have one group of opening and extend into the hollow region of first hollow circular cylinder, thereby make supercritical fluid spray to the cylindrical inwall of rotor with the perpendicular direction;
At least one input pipe that material is used, its end has one group of opening and extends into the hollow region of first hollow circular cylinder, thereby makes material flow spray to the cylindrical inwall of rotor with the perpendicular direction and converge at inwall with supercritical fluid from the ejection of the input pipe of shooting flow body and function basically;
Be arranged on the filter core of reative cell bottom;
Be arranged on the relief port on the shell, make supercritical fluid gasification and through the filter core filter bag walk and/discharge the liquid in the reative cell, thereby obtain dry product;
This method may further comprise the steps:
Open magnetic driver and drive the rotor rotation;
Supercritical fluid is sprayed to the inwall of first hollow circular cylinder of rotor with the perpendicular direction through the input pipe of described shooting flow body and function; Simultaneously with material flow pressurization after the input pipe that material is used, on the inwall of first hollow circular cylinder that sprays to the perpendicular direction, and converge with supercritical fluid;
Open the relief port, make supercritical fluid gasification and through the filter core filter bag walk and/discharge the liquid in the reative cell, thereby obtain dry product.
Be suitable for including, but are not limited to this, carbon dioxide, methane, ethane, ethene, propane, propylene and freon-13 (CClF as the material of supercritical fluid
3) etc., preferably carbon dioxide especially.
Some fluid critical properties that are commonly used for the supercritical fluid extraction solvent see the following form
| Material | Critical temperature Tc, K | Critical pressure Pc, MPa |
| Carbon dioxide | 304.2 | 7.37 |
| Ethane | 305.4 | 4.88 |
| Ethene | 282.4 | 5.04 |
| Propane | 369.8 | 4.25 |
| Propylene | 365.0 | 4.62 |
| Freon-13 (CClF 3) | 302.0 | 3.92 |
Supercritical fluid can at random contain one or more entrainers, for example, but is not limited thereto methyl alcohol, ethanol, isopropyl alcohol, acetone, chloroform, 1,1,1-trichloroethanes, 2,2,2-trifluoroethanol, triethylamine and 1,2-Bromofume etc.If you are using, entrainer preferably is no more than 30% of supercritical fluid, more preferably between 1～20%.
In the present invention, hypergravity is meant the centrifugal force that is produced by the rotor rotation except that gravity, be expressed from the next:
α=ω
2R, wherein ω is meant the angular speed of rotor, R is meant the mean radius of rotor.In reaction, the hypergravity level that the rotor rotation produces is controlled at 1.01-10000g, and (g is an earth acceleration, 9.8m/s
2), preferred 5-5000g, more preferably, 20-3000g, further preferred 100-500g.
In above-mentioned technology, fluid pressure is 1.01～7.0P
c, preferred 1.5-5P
c, temperature is 1.01～5.0T
c, preferred 1.5～3.0T
cP wherein
c, T
cBe respectively the supercritical pressure and the temperature of supercritical fluid.
In described technology, material liquid can be metallic particles, metallic compound, inorganic matter or organic matter (containing organic macromolecule), and high molecular solution is preferably organic matter, more preferably the solution of medicine or pharmaceutical carrier.
The rotating speed of the rotor of described hypergravity-supercritical reaction/crystallization apparatus is at about 500-5000r/min, and this depends on desired hypergravity level.
In above-mentioned technology, material can be a kind of material, also can be various materials charging simultaneously, and what be used with it is single fluid nozzle, two-fluid spray nozzle or multithread body nozzle.
In embodiments of the invention, material to be crystallized can be medical compounds or its mixture, for example, but is not limited thereto, and the cephalo-type chemical synthetic drug is as CEFUROXIME AXETIL, Cefixime, Cefepime, Cefradine; Protein and peptide medicament are as insulin, natural interferon, recombinant human interferon alpha 2, human growth hormone recombinant, human serum albumins, leuprolide acetate and salmon calcitonin; Salbutamol, lactose, gossypose, the dried alcohol etc. that reveals.In this case, appropriate solvent can be for example, but to be not limited thereto methyl alcohol, ethanol, isopropyl alcohol, acetone, N, dinethylformamide, N, N-dimethylacetylamide, 1,4-dioxane and dimethyl sulfoxide (DMSO) etc. or its any mixture.
Specifically, the invention provides a kind of crystallization processes in said apparatus, this technology may further comprise the steps:
Open magnetic driver and drive the rotor rotation;
Supercritical fluid sprays to the inwall of first hollow circular cylinder of rotor through the input pipe of shooting flow body and function; Simultaneously with the pressurization of the liquid of material to be crystallized after the input pipe that material is used, on the inwall of first hollow circular cylinder that sprays to the perpendicular direction, and converge with supercritical fluid;
Open the relief port, make supercritical fluid gasification and through the filter core filter bag walk and/discharge the liquid in the reative cell, thereby obtain dry crystalline material.
The solution of material to be crystallized be material to be crystallized as solute, as medicine, be dissolved in and obtain in the solvent.The scope that the concentration of material is more suitable is that doubly (S=0.01～0.99Sc), preferred 0.1-0.7 doubly, more preferably 0.2-0.5 doubly for the 0.01-0.99 of its saturation solubility Sc.
Used solvent depends on material to be crystallized in this technology, includes, but not limited to water, acetone, ethanol, isopropyl alcohol, ethyl acetate, ether, hexane and composition thereof.
The present invention also provides a kind of technology of reacting in said apparatus, this technology may further comprise the steps:
Open magnetic driver and drive the rotor rotation;
With supercritical fluid through the input pipe of shooting flow body and function inwall with first hollow circular cylinder that sprays to rotor; Simultaneously with the input pipe of using through first and second materials respectively after the pressurization of first reactant liquor and second reactant liquor, on the inwall of first hollow circular cylinder that sprays to the perpendicular direction, and converge with supercritical fluid;
After reaction finishes, open the relief port, make the supercritical fluid gasification and through the filter core filter bag walk and/discharge the liquid in the reative cell, thereby obtain dry crystalline material.
Below in conjunction with accompanying drawing the present invention is carried out concrete description.
A kind of concrete scheme of hypergravity-supercritical reaction of the present invention/crystallization apparatus as shown in Figure 1, it comprises upper end cover 7, bottom end cover 1, shell 6, filter core 2, high-gravity rotating bed 4, nozzle 5, magnetic driver 8, belt 9, belt pulley 10, motor 11.The cavity that upper end cover 7, bottom end cover 1 and shell 6 limit is a reaction/crystallisation chamber 12.The bottom section of reaction/crystallisation chamber 12 is a product jar 3.High-gravity rotating bed 4 are positioned at reaction/crystallisation chamber 12, and the upper end links to each other with the axle head of magnetic driver 8, and motor 11 rotates by the belt pulley that belt pulley 10 and belt 9 drive magnetic driver 8, and the rotating speed of motor 8 can be regulated by frequency modulation meter.
On upper end cover 7, be provided with on-condensible gas atmospheric valve interface/pressure tap a and be used for discharging the on-condensible gas of supercritical fluid.On upper end cover 7, be provided with relief valve connection g and prevent that chamber pressure is excessive.Also have temperature-measuring port h.On shell 6, be provided with supercritical fluid (supercritical fluid and entrainer or modifier) import b and material inlet e (and f).On bottom end cover 1, be provided with relief port c.
High-gravity rotating bed structure of the present invention as shown in Figures 2 and 3.Rotor is made of rotary drum 4-1, filler 4-2, core tube 4-3 and end cap 4-4.In Fig. 2, rotary drum 4-1, filler 4-2 and core tube 4-3 have constituted the cylinder of hollow.In Fig. 3, be one group of perforate cylinder of installing with one heart for the core tube, filler 4-2 is seated in the core tube at interval, be unkitted the again distributed area of the gap of filler as liquid phase, the core tube surface in distributed area has the combination of helicla flute, thread groove, wave groove, circumferential slot and axial groove or above several flutings again, helps liquid phase and is evenly distributed.Simultaneously, this structure helps making full use of the end effect of each layer filler, is suitable for the situation of big liquid measure.
The structure of filter core 2 of the present invention is rounding bench-type structure as shown in Figure 4, and the sealing surface of this structure is big, be easy to installation and removal.Filter core can adopt active carbon filter core, ceramic element, doughnut filter core, also can be the filter core that coats one or more layers membrane material.
Fig. 5 A-5D is the position sectional view of supercritical fluid and material flow input pipe.
In Fig. 5 A, supercritical fluid 5-2 and material flow 5-3 spray to direction of the first cylindrical inner surface 5-1, then spray to two positions of the first cylindrical inner surface 5-1 simultaneously among Fig. 5 B.
The spray regime schematic diagram of explanation supercritical fluid and two kinds of material flow among Fig. 5 C and the 5D.In Fig. 5 C, supercritical fluid 5-2 and two gangs of material flow 5-3 and 5-4 spray to a position of first cylindrical inner surface; And in Fig. 5 D, supercritical fluid 5-2 and two gangs of material flow 5-3 and 5-4 spray to two positions of first cylindrical inner surface.
Below with reference to technology of the present invention being described as Fig. 1 and Fig. 2.As shown in Figure 1, the material with certain pressure and temperature enters from material inlet e (and f) by certain flow, is sprayed onto the inner surface of high-gravity rotating bed 4 core tube 4-3 uniformly from the nozzle that links to each other with feed pipe; Meanwhile, supercritical fluid (supercritical fluid and modifier or entrainer) enters through supercritical fluid import b, and the nozzle through linking to each other with the supercritical fluid inlet tube sprays uniformly, and inner surface and the material of the core tube 4-3 high-gravity rotating bed 4 meet.Motor 11 drives magnetic driver 8 rotations by drive disk assembly belt pulley 10 and belt 9.Because high-gravity rotating bed 4 link together with the axle of magnetic driver 8, will be with the same rotating speeds rotation of magnetic driver 8, the rotating speed of motor 11 can be regulated by frequency modulation meter, the range of speeds 500～5000r/min.Under the effect of the high-gravity rotating bed 4 centrifugal and shearing forces that applied, two strands of materials reach desirable microcosmic admixture in filler 4-2, realize quick, homogeneous nucleation, and the material after the reaction/crystallization rests on reaction/crystallisation chamber bottom.After the regular hour, stop to enter of material and supercritical fluid, open the pressure-relief valve release at relief port c place, supercritical fluid moment this moment gasifies fast and takes away solvent, makes dry materials.Material (product) filters through filter core 2, is retained in the product jar 3.
The present invention joins together hypergravity and supercritical technology, has realized the dry integrated from being prepared into of ultra-fine/nano particle, and equipment volume is little, technological process is short.Can be used for the preparation of ultra-fine/Nano medication and pharmaceutical carrier etc.
When implementing method of the present invention, in concrete production the control parameter for example size and dimension depend on operating condition.Variable comprises supercritical fluid and/or contains the flow velocity of the carrier of material, material concentration and the particle in carrier and forms temperature and pressure in the container.
Fig. 6 is that hypergravity-supercritical reaction/crystallization apparatus is used for single flow chart of planting material.The CO that recycles in the system
2Gas with from CO
2The make-up gas of steel cylinder 1 is mixed mutually, goes into clarifier 2, the CO after the purification through filter is laggard
2Enter cooler 3 after the digital spinner flowmeter metering of gas through bearing high pressure, add modifier or entrainer if desired, then need to open modifier or entrainer pump 5, the modifier or the entrainer that come from modifier or entrainer jar 4 filter through filter, after the glass rotameter metering, be pressed into the import of supercritical fluid force (forcing) pump 6 by modifier or entrainer pump 5, together enter surge tank 7, after preheater 8 is preheating to the temperature of setting, enter hypergravity-supercritical reaction/crystallization apparatus 13 again; Meanwhile, material from material pot 9, after filtration, after the glass rotameter metering, enter the inlet of product pump 10, after the product pump pressurization, enter equalizer tank 11, and then be preheating to the temperature of setting through preheater 12 after, enter hypergravity-supercritical reaction/crystallization apparatus 13, with the supercritical fluid effect.The CO of entrapment solvent
2Gas flows out from the top of hypergravity-supercritical reaction/crystallization apparatus 13, after heat exchanger 14 heat exchange, after separator separates, recycles in system again.The product that obtains after reaction/crystallization, the drying is collected in the bottom of hypergravity-supercritical reaction/crystallization apparatus 13.
Fig. 7 is the flow chart that hypergravity-supercritical reaction/crystallization apparatus is used for two kinds/various materials.Charging is two kinds of materials as different from Example 1.Respectively from the material of material pot 9A and 9B, after filtration, after the glass rotameter metering, enter the inlet of product pump 10A and 10B, after the product pump pressurization, enter equalizer tank 11A and 11B, and then after preheater 12A and 12B are preheating to the temperature of setting, enter hypergravity-supercritical reaction/crystallization apparatus 13, with the supercritical fluid effect.The CO of entrapment solvent
2Gas flows out from the top of hypergravity-supercritical reaction/crystallization apparatus 13, after heat exchanger 14 heat exchange, after separator separates, recycles in system again.The product that obtains after reaction/crystallization, the drying is collected in the bottom of hypergravity-supercritical reaction/crystallization apparatus 13.If require the various materials charging, principle and operation are gone up identical with two kinds of material charging situations, and different is need add the corresponding material-transporting system identical with 9B, 10B, 11B and 12B can realize.
Process implementing example of the present invention
(1%, aqueous solution W/V) is after pressurizeing and CO will to be dissolved with pork insulin
2At 0.95MPa and 30 ℃ of inner surfaces (rotor as shown in Figure 2) that descend the while as the rotor of accompanying drawing 1 described equipment, the internal diameter of its core tube and the external diameter of rotary drum are respectively 20 and 70 millimeters.The control about 1000r/min of rotating speed (the hypergravity level be about 30g) (referring to 30 times of gravity, same down).Above-mentioned aqueous solution flow is 0.1ml/min, supercritical CO
2Flow is 10ml/min.After 30 minutes, open the relief port, filter, the average grain diameter of gained sample is 3.9 μ m, and it 1000 shows little photo and see Fig. 9.
Adopt embodiment 1 identical equipment and technology, will be dissolved with bovine serum albumin (1%, W/V) DMF solution and CO
2Under 1.00MPa and 30 ℃, be sprayed onto the inner surface of rotor simultaneously.The control rotating speed is about 1800r/min (the hypergravity level is about 100g).Solution flow rate is 0.1ml/min, supercritical CO
2Flow velocity is 10ml/min.The average grain diameter of gained sample is 3.8 μ m, and it 1000 shows little photo and see Figure 10 A.Bovine serum albumin raw material 1000 shows little photo and sees Figure 10 B.
Adopt embodiment 1 identical equipment and technology, will be dissolved with bovine serum albumin (1%, ethanolic solution W/V) and CO
2Under 1.00MPa and 30 ℃, be sprayed onto the inner surface of rotor simultaneously.The control rotating speed is about 2300r/min (the hypergravity level is about 150g).Solution flow rate is 0.1ml/min, supercritical CO
2Flow velocity is 10ml/min.The average grain diameter of gained sample is 3.8 μ m.
Adopt embodiment 1 identical equipment and technology, will be dissolved with papain (1%, W/V) DMF solution and CO
2Under 0.80MPa and 30 ℃, be sprayed onto the inner surface of rotor simultaneously.The control rotating speed is about 1800r/min (the hypergravity level is about 100g).Solution flow rate is 0.1ml/min, supercritical CO
2Flow velocity is 10ml/min.The average grain diameter of gained sample is 5 μ m, and it 1000 shows little photo and see Figure 11.
Adopt embodiment 1 identical equipment and technology, will be dissolved with Cefradine (3%, methanol solution W/W) and CO
2Under 1.00MPa and 35 ℃, be sprayed onto the inner surface of rotor simultaneously.The control rotating speed is about 2600r/min (the hypergravity level is about 200g).Solution flow rate is 0.1ml/min, supercritical CO
2Be 10ml/min.The average grain diameter of gained sample is 4.2 μ m, and it 1000 shows little photo and see Figure 12 A.Cefradine raw material 1000 shows little photo and sees Figure 12 B.
When the concentration of Cefradine is 3%, when system temperature was 35 ℃, pressure was seen Figure 13 A to the influence of particle diameter.When the concentration of Cefradine is 3%, 1.00MPa when system pressure is, temperature is seen Figure 13 B to the influence of particle diameter.1.00MPa when system pressure is, during 35 ℃ of temperature, the concentration of Cefradine is seen Figure 13 C to the influence of particle diameter.
Claims (17)
1. hypergravity-supercritical reaction/crystallization apparatus, it comprises:
The reative cell that limits by withstand voltage sealing shell;
Be positioned at the rotor with first hollow circular cylinder of reative cell, have aperture and/or groove on the first hollow circular cylinder inside and outside wall, fill filler between the first hollow circular cylinder inside and outside wall as fluid passage;
Be fixed on the shell, be connected with rotor to drive the magnetic driver of rotor rotation by axle;
The input pipe of shooting flow body and function, its end have one group of opening and extend into the hollow region of first hollow circular cylinder, thereby make supercritical fluid spray to the cylindrical inwall of rotor with the perpendicular direction;
At least one input pipe that material is used, its end has one group of opening and extends into the hollow region of first hollow circular cylinder, thereby makes material flow spray to the cylindrical inwall of rotor with the perpendicular direction and converge at inwall with supercritical fluid from the ejection of the input pipe of shooting flow body and function basically;
Be arranged on the filter core of reative cell bottom;
Be arranged on the relief port on the shell, make supercritical fluid gasification and through the filter core filter bag walk and/discharge the liquid in the reative cell, thereby obtain dry product.
2. reaction/crystallization apparatus according to claim 1, wherein said rotor also has and coaxial mounted second hollow circular cylinder of first hollow circular cylinder, the internal diameter of described second hollow circular cylinder is greater than the external diameter of first hollow circular cylinder, have aperture and/or groove on the described second hollow circular cylinder inside and outside wall as fluid passage, fill filler between the second hollow circular cylinder inside and outside wall.
3. reaction/crystallization apparatus according to claim 2, wherein said filler are woven wire, foam metal, plastic silk screen, foamed plastics, video disc, bead or spiral filling.
4. reaction/crystallization apparatus according to claim 2, wherein said filler are woven wire.
5. reaction/crystallization apparatus according to claim 2, wherein said filler are the ripple silk net in the woven wire.
6. reaction/crystallization apparatus according to claim 2, the groove that the wherein said first and/or second hollow circuit cylinder surface is opened is helicla flute, thread groove, wave groove, circumferential slot, axial groove, or the combination of various forms fluting.
7. reaction/crystallization apparatus according to claim 1, wherein: rotor is connected with the axle of magnetic driver.
8. reaction/crystallization apparatus according to claim 1, wherein: supercritical fluid is carbon dioxide, ethane, ethene, propane, propylene or a freon-13, and randomly has modifier or entrainer.
9. reaction/crystallization apparatus according to claim 1, wherein: supercritical fluid is a carbon dioxide.
10. reaction/crystallization apparatus according to claim 1, wherein: the filter core of product pot bottom can be active carbon filter core, ceramic element, doughnut filter core, also can be the filter core that coats one or more layers membrane material, membrane material comprises general membrane material, milipore filter material or NF membrane material.
11. one kind is carried out chemical reaction/crystallization processes in hypergravity-shooting flow precursor reactant/crystallization apparatus, this device comprises:
The reative cell that limits by withstand voltage sealing shell;
Be positioned at the rotor with first hollow circular cylinder of reative cell, have aperture and/or groove on the first hollow circular cylinder inside and outside wall, fill filler between the first hollow circular cylinder inside and outside wall as fluid passage;
Be fixed on the shell, be connected with rotor coaxial to drive the rotor drive shaft rotating;
The input pipe of shooting flow body and function, its end have one group of opening and extend into the hollow region of first hollow circular cylinder, thereby make supercritical fluid spray to the cylindrical inwall of rotor with the perpendicular direction;
At least one input pipe that material is used, its end has one group of opening and extends into the hollow region of first hollow circular cylinder, thereby makes material flow spray to the cylindrical inwall of rotor with the perpendicular direction and converge at inwall with supercritical fluid from the ejection of the input pipe of shooting flow body and function basically;
Be arranged on the filter core of reative cell bottom;
Be arranged on the relief port on the shell, make supercritical fluid gasification and through the filter core filter bag walk and/discharge the liquid in the reative cell, thereby obtain dry product;
This method may further comprise the steps:
Open magnetic driver and drive the rotor rotation;
Supercritical fluid is sprayed to the inwall of first hollow circular cylinder of rotor with the perpendicular direction through the input pipe of described shooting flow body and function; Simultaneously with material flow pressurization after the input pipe that material is used, on the inwall of first hollow circular cylinder that sprays to the perpendicular direction, and converge with supercritical fluid;
Open the relief port, make supercritical fluid gasification and through the filter core filter bag walk and/discharge the liquid in the reative cell, thereby obtain dry product.
12. technology according to claim 11, the hypergravity level that its rotor rotation produces is controlled at 1.01～10000g, and g is an acceleration of gravity, 9.8m/s
2
13. technology according to claim 11, the hypergravity level that its rotor rotation produces is controlled at 5-5000g, and g is an acceleration of gravity, 9.8m/s
2
14. technology according to claim 11, the hypergravity level that its rotor rotation produces is controlled at 20-3000g, and g is an acceleration of gravity, 9.8m/s
2
15. according to the technology of claim 12, wherein the pressure of supercritical fluid is 1.01～7.0P
c, temperature is 1.01～5.0T
cP wherein
c, T
cBe respectively the supercritical pressure and the temperature of supercritical fluid.
16. technology according to claim 11, wherein: supercritical fluid is carbon dioxide, ethane, ethene, propane, propylene or a freon-13, and randomly has modifier or entrainer.
17. technology according to claim 11, wherein: supercritical fluid is a carbon dioxide.
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| CN101549274B (en) * | 2008-04-01 | 2011-12-21 | 北京化工大学 | Supergravity revolving bed device and application in carbon dioxide collecting and purification process |
| CN106693858B (en) * | 2015-07-22 | 2019-09-13 | 北京化工大学 | A kind of block-resistant type is high-gravity rotating bed and contains the high-gravity rotating bed system and device of the block-resistant type and application |
| CN108283624B (en) * | 2017-01-10 | 2021-01-12 | 北京化工大学 | Sorafenib nano liposome preparation and preparation method thereof |
| CN112774611B (en) * | 2021-01-18 | 2024-01-30 | 广西大学 | Super-gravity micro-interface mass transfer strengthening reaction-crystallization drying coupling integrated machine |
| CN114082391B (en) * | 2021-11-12 | 2023-04-07 | 武汉科技大学 | Self-stabilizing baffling type super-gravity rotating bed |
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| CN1038578C (en) * | 1995-05-26 | 1998-06-03 | 北京化工大学 | Ultra-fine calcium carbonate preparation method |
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| CN1038578C (en) * | 1995-05-26 | 1998-06-03 | 北京化工大学 | Ultra-fine calcium carbonate preparation method |
| CN1428189A (en) * | 2001-12-28 | 2003-07-09 | 中国石油化工股份有限公司 | High-pressure rotary bed gas-liquid mass-transferring and reaction equipment in superheavy force field |
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