WO2010115377A1 - 微通道套管式装置及其应用 - Google Patents

微通道套管式装置及其应用 Download PDF

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Publication number
WO2010115377A1
WO2010115377A1 PCT/CN2010/071651 CN2010071651W WO2010115377A1 WO 2010115377 A1 WO2010115377 A1 WO 2010115377A1 CN 2010071651 W CN2010071651 W CN 2010071651W WO 2010115377 A1 WO2010115377 A1 WO 2010115377A1
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WIPO (PCT)
Prior art keywords
microchannel
nozzle core
inner nozzle
drugs
channel
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PCT/CN2010/071651
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English (en)
French (fr)
Inventor
沈志刚
甄崇礼
陈建峰
初广文
Original Assignee
北京化工大学
新加坡纳米材料科技公司
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Application filed by 北京化工大学, 新加坡纳米材料科技公司 filed Critical 北京化工大学
Priority to US13/263,833 priority Critical patent/US9156015B2/en
Publication of WO2010115377A1 publication Critical patent/WO2010115377A1/zh

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00Mixers with shaking, oscillating, or vibrating mechanisms
    • B01F31/80Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations
    • B01F31/86Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations with vibration of the receptacle or part of it
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30Micromixers
    • B01F33/301Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions
    • B01F33/3012Interdigital streams, e.g. lamellae
    • B01F33/30121Interdigital streams, e.g. lamellae the interdigital streams being concentric lamellae
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00Other mixers; Mixing plants; Combinations of mixers
    • B01F33/80Mixing plants; Combinations of mixers
    • B01F33/82Combinations of dissimilar mixers
    • B01F33/821Combinations of dissimilar mixers with consecutive receptacles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/90Heating or cooling systems
    • B01F35/92Heating or cooling systems for heating the outside of the receptacle, e.g. heated jackets or burners
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0093Microreactors, e.g. miniaturised or microfabricated reactors
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781Aspects relating to microreactors
    • B01J2219/00788Three-dimensional assemblies, i.e. the reactor comprising a form other than a stack of plates
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781Aspects relating to microreactors
    • B01J2219/00889Mixing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B22CASTING; POWDER METALLURGY
    • B22FWORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
    • B22F2998/00Supplementary information concerning processes or compositions relating to powder metallurgy
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00Fluid handling
    • Y10T137/0318Processes

Definitions

  • Microchannel cannula device and its application This application claims priority to Chinese Patent Application No. 200910131858.0, filed on April 9, 2009, entitled “Microchannel cannula device and its application” The entire contents of which are incorporated herein by reference.
  • Technical field
  • the present invention relates to an apparatus for enhancing mixing, mass transfer, heat transfer and reaction.
  • it relates to a microchannel cannula device that enhances mixing, mass transfer, heat transfer and reaction, and applications thereof.
  • Nano- and micro-structured particles such as metal oxides, organic compounds, inorganic compounds, and drug particles have great applications in microelectronics, information, aerospace, chemical, mechanical, automotive, and pharmaceutical fields.
  • the preparation methods of nano- and micro-structured particles are divided into physical methods and chemical methods, whether physical or chemical, and the precipitation method is most commonly used.
  • the conventional precipitation method usually uses a stirred tank as a reactor or a sedimentation device. Since the characteristics of the stirred tank itself are difficult to ensure rapid mixing, mass transfer and heat transfer between the reactant materials, the particle size generated after the precipitation is not Both, the precipitation or reaction time is too long, and the production efficiency is not high. The reason is due to the uneven mixing of ML in the main reactor or sedimentation equipment.
  • the present invention provides a microchannel cannula device comprising an inner nozzle channel (4), an outer nozzle channel (5) and a mechanical probe (8), wherein the outer nozzle channel (5) substantially concentrically surrounds a nozzle passage (4), the inner nozzle passage (4) substantially concentrically surrounds the mechanical probe (8), and the inner nozzle passage (4) is extended at its outlet portion to form an inner nozzle core (9), and an outer nozzle passage (5) After the outlet portion is contracted, an outer nozzle core (10) is formed, the outer nozzle core (10) substantially concentrically surrounds the inner nozzle core (9), and the mechanical probe (8) is configured to intermittently empty the inner nozzle core (9) .
  • microchannel tube-type device wherein the mechanical probe (8) is a hollow structure to allow high pressure gas to enter and clear the inner nozzle core (9) intermittently through the mechanical probe (8).
  • microchannel tube-type device wherein the mechanical probe (8) is a solid structure configured to intermittently enter and empty the inner nozzle core (9).
  • microchannel cannula device according to the present invention, wherein the mechanical probe
  • the frequency of emptying the inner nozzle core (9) is 1 ⁇ 200 times/min.
  • microchannel cannula device wherein the inner nozzle core
  • the outlet of (9) is substantially flush with the outlet of the outer nozzle core (10), or the outlet of the inner nozzle core (9) is located within the outlet of the outer nozzle core (10).
  • the microchannel cannula device further includes a temperature control jacket (6) surrounding the outer nozzle channel (5).
  • the microchannel cannula device further comprises a collector (11) surrounding the outlet of the outer nozzle core (10) and the outlet of the inner nozzle core (9) .
  • the microchannel cannula device further includes an ultrasonic probe disposed outside the end of the collector (11) to prevent particle condensation in the collector (11) And/or ⁇ : formed particle agglomerates.
  • the inner nozzle core (9) has a circular hole, a square hole or a regular triangular hole, and the inner nozzle core (9) has a diameter or a side of the passage hole
  • the length is 0.01 ⁇ 5mm
  • the outer nozzle core (10) surrounds the inner nozzle core
  • the gap size of (9) is 0.01 ⁇ 5mm.
  • Some embodiments of the microchannel tube-type device according to the present invention wherein the two fluids at the outlets through the inner nozzle core (9) and the outer nozzle core (10) each independently have a flow rate of 0.01 to 50 m/s, Volume flow from 0.01 to 500 L/min, and 1000 to 100,000 Reynolds number.
  • the present invention also provides a microchannel cannula device comprising a plurality of microchannel cannula devices in parallel as described above.
  • the invention provides the use of the microchannel cannula device according to any of the above, in the preparation of inorganic, organic or pharmaceutical particles having a nano or micro structure using a liquid-liquid system.
  • the metal oxide nanoparticle is prepared by a liquid-liquid precipitation method
  • the metal ion salt solution is introduced into the inner nozzle channel (4)
  • the precipitant solution is introduced into the outer nozzle
  • the channel (5), the metal ion salt solution and the precipitant solution are mixed after exiting the outlet of the inner nozzle core (9) and the outlet of the outer nozzle core (10), reacting to form a suspension, and optionally, the suspension is dried to obtain A powder product of metal oxide nanoparticles.
  • microchannel cannula device wherein the drug particles are prepared by a liquid-liquid precipitation method, and the drug solution in which the drug is dissolved is introduced into the inner nozzle channel (4) to contain an anti-solvent which is miscible with the drug solution.
  • the solution passes into the outer nozzle passage (5), and the drug solution and the anti-solvent dissolve 3 ⁇ 4 ⁇ away from the inner nozzle core (9) outlet and the outer nozzle core (10) outlet, mix, precipitate to form a suspension, and optionally, the suspension After drying, a powder product of drug particles is obtained.
  • microchannel tube-type device wherein one or more auxiliaries are added to the suspension.
  • microchannel tube-type device wherein the drying is in-line spray drying or in-line freeze drying.
  • microchannel cannula device wherein the drug is selected from the group consisting of: analgesics, anti-inflammatory drugs, anti-angina drugs, antiarrhythmic drugs, antibiotic drugs, antiparasitic drugs, anticoagulant drugs , antidepressant, antidiabetic, anti Fungal drugs, antihistamines, antihypertensive drugs, antimuscarinic drugs, anticonvulsants, antimigraine drugs, antiparasitic drugs, antiparkinson drugs, antipsychotics, hypnotics, sedatives, antibiotics Stroke drugs, antithrombotic drugs, anti-cough drugs, antiviral drugs, ⁇ -adrenergic receptor blockers, calcium channel blockers, vasoconstrictors, birth control pills, corticosteroids, dermatology drugs, disinfectants , diuretics, gastrointestinal drugs, general anesthetics, hemostatic agents, local anesthetics, opioid analgesics, parasympathomimetic drugs
  • microchannel cannula device wherein the drug is selected from the group consisting of: filbertib, cefuroxime axetil, azithromycin, lopinavir, cyclosporin, bikaru Amine, sedative acetate, levodopa, ciprofloxacin, camptothecin, danazol, naproxen, silybin, itraconazole and ruthenium.
  • the drug is selected from the group consisting of: filbertib, cefuroxime axetil, azithromycin, lopinavir, cyclosporin, bikaru Amine, sedative acetate, levodopa, ciprofloxacin, camptothecin, danazol, naproxen, silybin, itraconazole and ruthenium.
  • microchannel cannula device wherein the adjuvant is selected from the group consisting of: a filler, a diluent, a binder, a lubricant and a disintegrant.
  • the adjuvant is selected from the group consisting of: a filler, a diluent, a binder, a lubricant and a disintegrant.
  • the microchannel cannula device includes a first inlet tube, a second inlet tube, an inner nozzle, an outer nozzle, a temperature control jacket, and a collector; wherein the inner nozzle is configured by the inner nozzle fluid passage and the inner nozzle a nozzle core, the inner nozzle is a first microchannel carrying a raw material liquid stream; the outer nozzle is composed of an outer nozzle fluid passage and an outer nozzle core, the outer nozzle is a second microchannel carrying a raw material liquid stream; the outer nozzle nozzle core is fitted a nozzle core surrounding the inner nozzle, the inner and outer nozzles form a sleeve structure; the temperature control jacket is disposed outside the outer nozzle for controlling the temperature of the whole device and the two streams before and after mixing; a collector is arranged at the lower end of the device One of the two different liquid streams passes through the first inlet tube, the inner nozzle fluid passage and the inner nozzle core, and the other liquid stream passes through the second inlet tube, the outer nozzle fluid
  • the passage of the inner nozzle core is a hole
  • the hole is one of a circular hole, a square hole or a regular triangular hole, and the diameter or the side length of the inner nozzle core passage hole is generally
  • the gap size of the outer nozzle core around the inner nozzle core is 0.01 ⁇ 5mm.
  • the fluid flow rate through the inner and outer nozzle core outlets is generally 0.01 ⁇ 50m / s, the fluid volume flow rate is 0.01 ⁇ 500 L / min, and the Reynolds number is 1000 ⁇ 100 000.
  • the collector is an annular conical tube structure.
  • the medium in the temperature control jacket may be selected according to the requirements of a specific process.
  • a mechanical probe is further provided to effectively prevent or remove particles on the nozzle core to ensure that the microchannels in the device are always unblocked, thereby continuously preparing nanometer-sized structural particles.
  • the mechanical probe in the apparatus is a hollow structure that periodically presses the microchannels of the nozzle core under high pressure by nitrogen to effectively prevent or remove particulate matter on the nozzle core and avoid clogging of the nozzle core.
  • the mechanical probe in the device is of a solid construction, in which case the probe is passed through the nozzle core by timing to achieve the purpose of unblocking the nozzle core. Whether it is a hollow structure or a solid structure, the speed at which the mechanical probe empties the nozzle core is as needed, usually 1 to 200 times/min.
  • the working principle of the mechanical probe is: for the solid structure mechanical probe, the control part of the mechanical probe is a spring device, the spring device is coupled with a gas passage, the gas passage is connected with a gas valve, and the other end of the valve is connected with high pressure nitrogen gas.
  • the valve is controlled by a computer program to be turned on and off periodically, and the opening time and the closing time can also be automatically controlled by the program. Once set, the power is turned on.
  • the gas valve is opened, the mechanical probe can probe down and clear the nozzle core due to pressure, avoiding and clearing the particles on the nozzle core.
  • the gas valve is closed, due to gas pressure Normal pressure is restored and the mechanical probe is restored to its original state due to the action of the spring.
  • the mechanical probe can periodically clear the nozzle core to achieve the continuous operation of the entire device.
  • the hollow probe tip is connected to a gas valve, and the other end of the valve is connected with high-pressure nitrogen.
  • the valve is controlled by a computer program to be turned on and off periodically, and the opening time and the closing time can also be automatically controlled by the program.
  • the power is turned on.
  • the gas valve is opened, the high-pressure nitrogen rapidly squeezes the nozzle core in an instant, avoiding and removing the particles on the nozzle core, and reaching the timing to clear the nozzle. Achieve continuous operation of the entire device.
  • an ultrasonic probe is placed externally at the end of the annular cone collector to further avoid and disperse agglomerates formed by the particles in the collector.
  • the collected streams in the collector are subjected to a further post-treatment operation to obtain a powder product having nano- and micro-structured particles.
  • the post-treatment operations include, but are not limited to, filtration and drying.
  • the invention provides a method for operating a microchannel cannulated device.
  • the invention provides a method of continuously preparing nano, micro-structured inorganic, organic or pharmaceutical particles.
  • the microchannel tube type micro-mixing and reacting device provided by the invention has the advantages of replacing the stirring tank and the like with a microchannel sleeve type device, effectively strengthening the liquid-liquid micro-mixing and subsequent reaction, and forming the particles formed by the precipitation reaction.
  • Uniform size in particular, further mechanical probes are provided to prevent or remove particulate matter on the nozzle core to ensure that the microchannels are always clear, and the ultrasonic probe is further arranged to further avoid agglomerates formed by dispersing and dispersing the particles, thereby achieving continuous production.
  • FIG. 1 is a schematic longitudinal sectional view showing a preferred microchannel cannula device for achieving the second object of the present invention.
  • Fig. 2 is a schematic longitudinal sectional view showing a multi-microchannel cannula device for realizing the second object of the present invention.
  • microchannel tube-type device of the present invention and the method of preparing the nano- and micro-structured particles are based on the theoretical and experimental results of the present inventors in the field.
  • the formation of nano- and micro-sized particles is first a phase change process, including two stages of nucleation and growth.
  • concentration of the new phase generated exceeds the critical nucleation concentration, a large number of new nuclei will be rapidly formed; at the same time, the concentration of the substance that causes the formation of the new phase will rapidly decrease, and the concentration at this time is insufficient to continue to form a new nuclei, but only maintain Nuclear growth.
  • a liquid stream rapidly enters the inner nozzle passage 4 from the first inlet pipe 2, and then the liquid flow is accelerated at the inner nozzle core 9 because the passage is further reduced.
  • the liquid stream quickly enters the outer nozzle channel 5 from the second inlet tube 3, where the liquid stream at the outer nozzle core 10 is further reduced due to the passage of the liquid stream.
  • the two fluids flow at the outlet of the nozzle core to form a high-speed micro-liquid flow, collide and rapidly micro-mix and precipitate, and finally merge into the annular cone collector 11 and then flow out.
  • the shape of the passage holes of the inner nozzle core 9 can be varied, including but not limited to circular holes, square holes or regular triangular holes. If it is a circular hole, then The diameter of the hole ranges from 0.01 to 5 mm. If the hole is a square hole, the length of the hole ranges from 0.01 to 5 mm. If the hole is a regular triangular hole, the length of the hole ranges from 0.01 to 5 mm. The shape of the outer nozzle core microchannel is matched and surrounds the inner nozzle core, and the gap size ranges from 0.01 to 5 mm.
  • the nozzle core of the outer nozzle cooperates with the nozzle core of the inner nozzle, and the flow formed by the rapid fluid micro-mixing of the fluid from the inner nozzle core with the fluid from the outer nozzle core maintains the mixing zone formed by the main direction of the raw material liquid stream of the first microchannel .
  • the flow rate (V) of the two fluids at the outlet of the inner nozzle core 9 and the outer nozzle core 10 ranges from 0.01 to 50 m/s, and the volume flow rate (Q) ranges from 0.01 to 500 L/min.
  • the Reynolds number (Re) ranges from 1000 to 100 000.
  • Re p vL/ ⁇ , where ⁇ , ⁇ and V are the density, viscosity and flow rate of the fluid, respectively, and L is the diameter or equivalent diameter of the microchannel pores.
  • the outlet of the inner nozzle core (9) and the outlet of the outer nozzle core (10) are substantially flush, or the outlet of the inner nozzle core (9) is located within the outlet of the outer nozzle core (10) for more efficient Enables rapid micro-mixing of fluids.
  • the nozzle core is blocked, thereby ensuring continuous normal operation of the microchannel cannula device, and the device is provided with an organic probe 8 .
  • the mechanical probe can be either a solid structure or a hollow structure.
  • a hollow structure maintaining the continuous normal operation of the nozzle core is achieved by squeezing the microchannel of the nozzle core under high pressure by nitrogen timing.
  • the mechanical probe 8 is passed through the nozzle core by timing to achieve the purpose of unblocking the nozzle core. Whether it is a hollow structure or a solid structure, the mechanical probe 8 empties the nozzle core at a speed of 1 to 200 times/min.
  • the ultrasonic probe 13 is externally disposed at the end of the annular cone collector 11 to disperse the captured suspension. And anti-agglomeration.
  • a plurality of microchannel cannula devices can also be connected in parallel, so that in the industrial implementation, a liquid and b liquid achieve the same microscopic mixing effect, and can reliably Realize the industrial production of products.
  • the a liquid and the b liquid in the present invention are mixed A solution in which a reaction occurs to form a precipitate.
  • a liquid may be a metal salt solution
  • b liquid is a precipitant solution
  • the metal salt solution may be a metal acetate, a chloride salt, a nitrate salt, a phosphate salt, a sulfate salt or a carbonate salt, or a mixture of the above various metal salts.
  • the precipitating agent solution may be an alkali solution such as an inorganic alkali solution such as sodium hydroxide, potassium hydroxide or ammonium hydroxide, or an organic alkali solution such as tetradecyl ammonium hydroxide or a mixture of the above various alkali solutions.
  • an alkali solution such as an inorganic alkali solution such as sodium hydroxide, potassium hydroxide or ammonium hydroxide, or an organic alkali solution such as tetradecyl ammonium hydroxide or a mixture of the above various alkali solutions.
  • a liquid is a mixed solution of BaCl 2 and TiCl 4 and b liquid is a NaOH solution.
  • the molar ratio of Ba/Ti in a liquid is 1.05, and the concentration of Ti 4+ particles in solution a is 0.5 mol L. b
  • the concentration of Off in the liquid is 3.0 mol L.
  • the volumetric flow ratio of a liquid and b liquid into the respective inlet pipes is 1:1, the volume flow rate is 20 L/h, and the flow rate is 2 m/s.
  • the reaction temperature is controlled at 90 by the temperature control jacket 6.
  • the suspension which is recirculated from the annular cone collector 11 is filtered and dried to obtain a powder product of BaTiO 3 nanoparticles.
  • the particle size of the barium titanate particles was measured by TEM to be 30 ⁇ 10 legs.
  • a liquid is a drug solution and b liquid is an anti-solvent.
  • the anti-solvent solution means that the solvent in the anti-solvent solution and the solvent in the drug solution are mutually soluble, but the solubility of the drug solution in the anti-solvent solution is extremely low or almost insoluble. When the drug solution and the anti-solvent solution are mixed, precipitation may occur due to a change in solubility.
  • the drugs are selected from the following drugs: analgesics, anti-inflammatory drugs, anti-angina drugs, antiarrhythmic drugs, antibiotic drugs, antiparasitic drugs, anticoagulants, antidepressants, antidiabetic drugs, antifungals Drugs, antihistamines, antihypertensives, antimuscarinic drugs, anti-praline drugs, anti-migraine drugs, anti-parasitic drugs, anti-Parkinson drugs, antipsychotics, hypnotics, sedatives, anti-stroke Drugs, antithrombotic drugs, anti-cough drugs, antiviral drugs, P-adrenergic receptor blockers, calcium channel blockers, vasoconstrictors, birth control pills, corticosteroids, dermatological drugs, disinfectants, diuretic Agent, gastrointestinal drug, general anesthetic, hemostatic, local anesthetic, opioid analgesic, parasympathomimetic, peptide, sex hormone, steroid, inducer, vasodilator,
  • the drug in drug solution a is selected from the group consisting of: filbertib, cefuroxime axetil, azithromycin, lopinavir, cyclosporine, sedative acetate Karruzide, levodopa, ciprofloxacin, camptothecin, danazol, naproxen, silybin, itraconazole.
  • the solvent in the drug solution a is one of a mixture of decyl alcohol, ethanol, acetone, n-propanol, isopropanol or the above solvent.
  • the anti-solvent in the anti-solvent solution is water.
  • At least one or more auxiliaries are added to the drug solution 3, the anti-solvent solution b, or the suspension formed by micro-channel cannula micro-mixing and the reaction device to form a precipitate.
  • the additive is added to the solution of the solution drug solution a, the anti-solvent solution b or the micro-channel cannulated micro-mixing and reaction device to form a precipitate, the self-filling agent (diluent) , additives such as binders, lubricants and disintegrants are selected.
  • the additive is added to the solution of the solution drug solution a, the anti-solvent solution b or the suspension formed by the microchannel cannula micro-mixing and the reaction device, from the lactose, the microcrystalline cellulose , mannitol, dextrin, hydroxypropyl hydrazine, povidone, sodium carboxycarboxylated cellulose, conjugated povidone, polyvinyl alcohol, magnesium lauryl sulfate and sodium dodecyl sulfate And so on.
  • the drug solution a is formed by dissolving 20 g of filbertib and 0.5 g of sodium lauryl sulfate in 200 ml of ethanol, before entering the inlet tube I(2), the drug solution a
  • the temperature is controlled at 35 °C.
  • the anti-solvent solution b is prepared by dissolving 76 g of lactose, 2 g of hydroxypropionin-E3 and 1.5 g of sodium lauryl sulfate in 2 L of water, and the temperature of the anti-solvent solution b is controlled before entering the inlet tube II (3). 4 °C.
  • the flow ratio of the drug solution a and the anti-solvent solution b to the respective inlet tubes was 1:10.
  • the flow rate of the filbertib solution into the inlet tube I ( 2 ) was 2 L/hr.
  • the flow rate of the filbertib solution into the inlet tube I ( 2 ) was lm/s.
  • the suspension which flows into the annular cone collector (11) and then flows out is dried by a spray dryer to obtain particles containing nano-Filobert particles and auxiliary agents.
  • Powder. Flobeite in powder The particle size SEM test was 300 ⁇ 100 nm. The filocate granules in the powder are well dispersed in the auxiliaries.
  • the final filbertib powder can be used in the formulation to improve the bioavailability of the filbertibide formulation.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Medicinal Preparation (AREA)

Description

微通道套管式装置及其应用 本申请要求于 2009 年 4 月 9 日提交中国专利局、 申请号为 200910131858.0.发明名称为"微通道套管式装置及其应用 "的中国专 利申请的优先权, 其全部内容通过引用结合在本申请中。 技术领域
本发明涉及一种强化混合、传质、传热与反应的装置。具体而言, 涉及一种强化混合、传质、传热与反应的微通道套管式装置及其应用。 背景技术
纳、 微米结构的颗粒如金属氧化物、 有机化合物、 无机化合物、 药物颗粒在微电子、 信息、 航天、 化工、 机械、 汽车、 药物等诸多领 域都有着巨大的应用。纳、微米结构颗粒的制备方法分为物理法和化 学法, 无论是物理法还是化学法, 其中沉淀法最为常用。 然而, 常规 的沉淀法通常采用搅拌釜作为反应器或沉淀设备,由于搅拌釜本身的 特点很难保证反应物物料之间快速的混合、传质和传热, 因此导致沉 淀后生成的颗粒大小不均, 沉淀或反应的时间过长, 生产效率不高。 究其原因, 主要 应器或沉淀设备内 ML混合不均所致。
针对搅拌釜上述问题的缺陷,为了强化沉淀法中涉及的混合和传 质, 陈建峰等人借鉴 Ramshaw等人发明的采用旋转填充床用于提高 气-液传质效率的一种工艺 ( US. Pat. No. 4283255 ), 通过采用并改 进旋转填充床(也称为超重力反应器, 中国专利号 ZL95215430.7 ) 作为反应器, 发明了一种制备超细碳酸钙的方法 (中国专利号 ZL95105343.4 )„ 该方法缩短了碳化反应时间, 并使颗粒纳米化, 粒 径可以控制在 10 ~ 40nm之间, 粒径分布均匀。 然而, 由于超重力反 应器中转子多采用填料层的形式,对于高粘度物料的沉淀、结晶过程, 运行过程会出现堵塞状况, 需要经常清洗, 不利于连续操作。
因此有必要提供一种强化液-液微观混合与反应,可连续制备具 有纳、 微米结构的无机、 有机或药物颗粒的装置。 发明内容
在一个方面,本发明提供一种微通道套管式装置, 包括内喷嘴通 道(4)、 外喷嘴通道(5)和机械探针(8), 其中外喷嘴通道(5)基 本同心地环绕内喷嘴通道(4), 内喷嘴通道(4)基本同心地环绕机 械探针(8), 内喷嘴通道(4)在其出口部收缩后延伸形成内喷嘴芯 (9), 外喷嘴通道(5)在其出口部收缩后延伸形成外喷嘴芯 (10), 外喷嘴芯(10)基本同心地环绕内喷嘴芯 (9), 机械探针(8) 经配 置能够间歇地清空内喷嘴芯(9)。
根据本发明的微通道套管式装置的一些实施方案,其中机械探针 ( 8 )是空心结构以允许高压气体间歇地通过机械探针 ( 8 )进入并清 空内喷嘴芯(9)。
根据本发明的微通道套管式装置的一些实施方案,其中机械探针 (8)是实心结构, 经配置能够间歇地进入并清空内喷嘴芯(9)。
根据本发明的微通道套管式装置的一些实施方案,其中机械探针
(8)清空内喷嘴芯 (9)的频率是 1~200次 /分钟。
根据本发明的微通道套管式装置的一些实施方案,其中内喷嘴芯
(9) 的出口和外喷嘴芯 (10)的出口基本平齐, 或者内喷嘴芯 (9) 的出口位于外喷嘴芯(10) 的出口以内。
根据本发明的微通道套管式装置的一些实施方案,所述微通道套 管式装置还包括环绕在外喷嘴通道(5)周围的控温夹套(6)。
根据本发明的微通道套管式装置的一些实施方案,所述微通道套 管式装置还包括环绕在外喷嘴芯 (10) 的出口和内喷嘴芯 (9)的出 口周围的收集器(11)。
根据本发明的微通道套管式装置的一些实施方案,所述微通道套 管式装置还包括设置在收集器( 11 )末端外置的超声探头以在收集器 (11) 中避免颗粒的凝并和 /或^:已形成的颗粒团聚体。
根据本发明的微通道套管式装置的一些实施方案,其中所述内喷 嘴芯 (9)的通道为圆形孔、 正方形孔或正三角形孔, 内喷嘴芯 (9) 通道孔的直径或边长为 0.01~5mm, 外喷嘴芯 (10)环绕内喷嘴芯 ( 9 ) 的间隙尺寸为 0.01 ~ 5mm。
根据本发明的微通道套管式装置的一些实施方案,其中通过所述 内喷嘴芯(9 )和外喷嘴芯 (10 ) 出口处的两股流体各自独立地具有 0.01 ~ 50m/s的流速, 0.01 ~ 500 L/min的体积流量,和 1000 ~ 100000 雷诺数。
在另一方面,本发明还提供一种微通道套管式装置,其由多个根 据上述的所述微通道套管式装置并联在一起组成。
在另一方面,本发明还提供根据上述任意一项的所述微通道套管 式装置在利用液-液体系制备具有纳、微米结构的无机、有机或药物 颗粒中的用途。
根据本发明的所述微通道套管式装置的用途,其中采用液 -液沉 淀法制备金属氧化物纳米颗粒, 将金属离子盐溶液通入内喷嘴通道 ( 4 ), 将沉淀剂溶液通入外喷嘴通道( 5 ),金属离子盐溶液和沉淀剂 溶液在离开内喷嘴芯 (9 ) 出口和外喷嘴芯 (10 ) 出口后混合、 反应 形成悬浮液, 以及任选地,该悬浮液经干燥后得到金属氧化物纳米颗 粒的粉体产品。
根据本发明的所述微通道套管式装置的用途,其中采用液 -液沉 淀法制备药物颗粒, 将溶解有药物的药物溶液通入内喷嘴通道(4 ), 将含有与药物溶液互溶的反溶剂溶液通入外喷嘴通道( 5 ), 药物溶液 和反溶剂溶¾ ^离开内喷嘴芯 (9 ) 出口和外喷嘴芯 (10 ) 出口后混 合、 沉淀形成悬浮液, 以及任选地, 该悬浮液干燥后得到药物颗粒的 粉体产品。
根据本发明的所述微通道套管式装置的用途,其中在所述悬浮液 中添加一种或多种助剂。
根据本发明的所述微通道套管式装置的用途,其中所述干燥是在 线喷雾干燥或在线冷冻干燥。
根据本发明的所述微通道套管式装置的用途, 其中所述药物选 自: 镇痛药物, 消炎药物, 抗心绞痛药物, 抗心律失常药物, 抗生素 药物, 抗寄生虫药物, 抗凝血药物, 抗抑郁药物, 抗糖尿病药物, 抗 真菌药物,抗组胺药物,抗高血压药物,抗毒蕈碱药物,抗赘疣药物, 抗偏头痛药物, 抗寄生物药物, 抗帕金森药物, 抗精神病药物, 催眠 药, 镇静药, 抗中风药物, 抗血栓药物, 抗咳散药物, 抗病毒药物, β -肾上腺素受体阻断剂,钙离子通道阻断剂,血管收缩药,避孕药, 皮质甾体,皮肤科药物, 消毒药物, 利尿剂, 胃肠道用药,全麻药物, 止血剂,局麻药, 阿片类镇痛药, 拟副交感神经药物, 肽类, 性激素, 甾体, 诱导剂, 血管扩张剂, 一氧化氮制剂, 制剂可用的酸、 碱及盐 衍生物, 空间异构衍生物。
根据本发明的所述微通道套管式装置的用途, 其中所述药物选 自: 菲洛贝特, 头孢呋辛酯, 阿奇審素, 洛匹那韦, 环孢審素, 比卡 鲁胺, 醋酸曱地孕酮, 左旋多巴, 环丙沙星, 喜树碱, 达那唑, 奈普 生, 水飞蓟宾, 伊曲康唑和罗红審素。
根据本发明的所述微通道套管式装置的用途, 其中所述助剂选 自: 填充剂、 稀释剂, 黏合剂, 润滑剂和崩解剂。
在另一方面, 本发明的目的是提供一种强化混合、传质、传热及 反应的微通道套管式装置。
在一个实施方案中,微通道套管式装置包括第一进液管、第二进 液管、 内喷嘴、 外喷嘴、 控温夹套和收集器; 其中, 内喷嘴由内喷嘴 流体通道和内喷嘴芯构成, 内喷嘴为承载原料液体物流的第一微通 道; 外喷嘴由外喷嘴流体通道和外喷嘴芯构成,外喷嘴为承载原料液 体物流的第二微通道; 外喷嘴的喷嘴芯配合并环绕内喷嘴的喷嘴芯, 内、外喷嘴形成套管式结构; 控温夹套设置在外喷嘴的外面, 用于控 制整个装置和两股物流混合前、后的温度; 装置下端设一收集器, 两 股不同液体物流的其中一股通过第一进液管、内喷嘴流体通道和内喷 嘴芯, 另外一股液体物流通过第二进液管、外喷嘴流体通道和外喷嘴 芯,快速微观混合,混合后的物流被收集器捕集、緩冲和进一步混合。
在一个实施方案中, 内喷嘴芯的通道为孔, 该孔为圆形孔、正方 形孔或正三角形孔中的一种孔,内喷嘴芯通道孔的直径或边长一般为
0.01 ~ 5mm, 外喷嘴芯环绕内喷嘴芯的间隙尺寸为 0.01 ~ 5mm。 通过所述内、 外喷嘴芯出口处的流体流速一般为 0.01 ~ 50m/s, 流体体积流量为 0.01 ~ 500 L/min, 雷诺数为 1000 ~ 100 000。
在一个优选实施方案中, 收集器为环形锥管结构。
所述控温夹套中的介质根据具体过程的要求进行选择即可。 在另一方面,本发明的目的是提供一种可以连续操作的具有强化 混合、 传质、 与传热及反应的微通道套管式装置。
在一个实施方案中,在实现前述目的装置基础上,进一步设置有 机械探针,有效预防或清除喷嘴芯上的颗粒物, 以保证装置中的微通 道一直畅通, 从而连续制备纳微米结构颗粒的目的。
在一个实施方案中,装置中机械探针为空心结构,该探针通过氮 气定时在高压作用下挤压喷嘴芯的微通道,有效预防或清除喷嘴芯上 的颗粒物,避免喷嘴芯的堵塞。在所述第二目的的一个更详细的实施 方案中,装置中机械探针为实心结构,此时该探针通过定时向下探伸 穿过喷嘴芯来达到疏通喷嘴芯的目的。 无论是空心结构还是实心结 构, 机械探针清空喷嘴芯的速度根据需要而定, 通常为 1 ~ 200 次 /min.
所述机械探针的工作原理是:对于实心结构机械探针,在机械探 针顶端控制部分为一弹簧装置,该弹簧装置联接有一气体通道, 气体 通道联接一气体阀门, 阀门另一端联接高压氮气,该阀门由计算机程 序控制可以定时开启和关闭,同时开启时间和关闭时间也可以由程序 自动控制。 一 呈序设定, 接通电源, 当气体阀门开启时, 机械探针 由于压力作用可以向下探伸、疏通喷嘴芯,避免和清除喷嘴芯上的颗 粒, 当气体阀门关闭时, 由于气体压力恢复常压, 机械探针因为弹簧 作用恢复原状。这样,机械探针就可以定时疏通喷嘴芯来达到整个装 置连续运行的目的。对于空心结构的机械探针, 空心的探针顶端联接 一气体阀门, 阀门另一端联接高压氮气,该阀门由计算机程序控制可 以定时开启和关闭, 同时开启时间和关闭时间也可以由程序自动控 制。 一旦程序设定, 接通电源, 当气体阀门开启时, 高压氮气在瞬间 迅速挤压喷嘴芯, 避免和清除喷嘴芯上的颗粒, 达到定时疏通喷嘴, 实现整个装置连续运行。在所述第二目的的一个实施方案中,在环形 锥管收集器末端外置超声探头,进一步避免和分散收集器中颗粒凝并 形成的团聚体。
在一个实施方案中,对收集器中汇集的物流进行进一步的后处理 操作, 得到具有纳、微米结构颗粒的粉体产品。 所述后处理操作包括 但不限于过滤和干燥。
在另一方面, 本发明提供一种用于操作微通道套管式装置的方 法。
在另一方面, 本发明提供一种连续制备纳、微米结构无机、有机 或药物颗粒的方法。
本发明提供的微通道管式微观混合与反应装置的优点表现在:用 微通道套管式装置替代搅拌釜等设备,有效地强化了液 -液微观混合 及后续反应,使沉淀反应生成的颗粒大小均匀;特别是进一步设置机 械探针预防或清除喷嘴芯上颗粒物以保证微通道一直畅通,设置超声 探头进一步避免和分散颗粒凝并形成的团聚体, 从而实现连续化生 产。 附图说明
通过阅读以下参照附图对非限制性实施例所作的详细描述,本发 明的其它特征、 目的和优点将会变得更明显。
图 1 所示为实现本发明第二目的的优选的微通道套管式装置的 纵剖面结构示意图。
图 2 所示为实现本发明第二目的的具有多重微通道套管式装置 的纵剖面结构示意图。
图中: 1.机械探针控制部分, 2.第一进液管, 3.第二进液管, 4. 内喷嘴通道, 5.外喷嘴通道, 6.控温夹套, 7.夹套介质入口, 8.机械探 针, 9.内喷嘴芯, 10.外喷嘴芯, 11.环形锥管收集器, 12.夹套介质出 口, 13·超声探头。 具体实施方式
在下面描述和图解本发明的示例性实施方案。该方案已包括在微 通道套管式装置及其使用方法中, 更具体地, 已包括在用于连续制备 纳微米结构无机、有机或药物颗粒的方法中。 当然, 对于本领域普通 技术人员来说显而易见的是,下面讨论的优选实施方案在本质上是示 例性的, 并且可以在没有偏离本发明的范围和精神的情况下被改变。 但是,为了清楚和准确, 下面讨论的所述示例性实施方案可以包括优 选的步骤、 方法和特征, 本领域普通技术人员将可以认识到, 这些优 选的步骤、 方法和特征不是落在本发明范围内的必要
本发明中微通道套管式装置以及涉及到的制备纳、微米结构颗粒 的方法是基于本发明人在该领域的理论和实验结果而来。
对于液相沉淀法制备纳、微米结构颗粒而言, 纳、微米结构颗粒 的形成过程, 首先是一个相变过程, 也包括成核和生长两个阶段。 当 两种能快速形成沉淀的溶液相遇时,在两种新鲜溶液的界面处,将伴 随扩散和相变的发生。 当生成的新相浓度超过临界成核浓度时,将迅 速形成大量新核; 同时成核导致形成新相的物质的浓度迅速下降,这 时的浓度不足以继续形成新核, 而只能维持已有核的生长。 因此要想 通过液 -液沉淀法制备纳、微米结构颗粒,就要保证液 -液相在混合 瞬间提供尽可能多的新鲜溶液相界面,这样生成的原生核总数目就越 多, 提供给核继续生长的浓度就低, 也为缩短颗粒生长时间、 减小粒 径提供条件。 而这一要求可以通过强化微观混合和传质来得以实现。 本发明正是以上述理论和原理为依据的。
下面参照附图 1和图 2进行详细描述。
具体操作时, a液体物流从第一进液管 2快速进入内喷嘴通道 4, 然后在内喷嘴芯 9处 a液体物流由于通道进一步变小而流速加快。 b 液体物流从第二进液管 3快速进入外喷嘴通道 5,在外喷嘴芯 10处 b 液体物流由于通道进一步变小而流速加快。两股流体在喷嘴芯出口处 并流形成高速微液流,撞击而迅速微观混合并沉淀,最后汇流于环形 锥管收集器 11再流出。
前述具体实施方式中,内喷嘴芯 9的通道孔的形状可以有多种变 化, 包括但不限于圆形孔、 正方形孔或正三角形孔。 若为圆形孔, 则 孔的直径大小范围为 0.01 ~ 5mm; 若孔为正方形孔, 则孔的边长大 小范围为 0.01 ~ 5mm; 若孔为正三角孔, 则孔的边长大小范围为 0.01 ~ 5mm。 而外喷嘴芯微通道的形状配合并环绕内喷嘴芯, 其间隙 尺寸范围为 0.01 ~ 5mm。 外喷嘴的喷嘴芯配合内喷嘴的喷嘴芯, 从 内喷嘴芯出来的流体与外喷嘴芯出来的流体快速微观混合后形成的 物流, 保持第一微通道的原料液体物流主方向所形成的混合区。
为达到快速微观混合的目的,两股流体在内喷嘴芯 9和外喷嘴芯 10出口处的流速(V ) 范围为 0.01 ~ 50 m/s, 体积流量(Q ) 范围为 0.01 - 500 L/min, 雷诺数 ( Re ) 范围为 1000 ~ 100 000。 这里 Re = p vL/ μ , 其中 ρ 、 μ和 V分别为流体的密度、 粘度和流速, L为微 通道孔的直径或当量直径。
在一些实施方案中, 内喷嘴芯 (9 ) 的出口和外喷嘴芯 (10 ) 的 出口基本平齐, 或者内喷嘴芯 (9 ) 的出口位于外喷嘴芯(10 ) 的出 口以内以便更加有效地使流体实现快速的微观混合。
为有效预防或清除喷嘴芯上因混合和沉淀而生成的颗粒物堵塞 喷嘴芯,从而保证微通道套管式装置的连续正常运行,装置设置有机 械探针 8。
机械探针可以是实心结构, 也可以是空心结构。 若为空心结构, 维持喷嘴芯连续正常运行是通过氮气定时在高压作用下挤压喷嘴芯 的微通道来实现。若为实心结构,则机械探针 8是通过定时向下探伸 穿过喷嘴芯来达到疏通喷嘴芯的目的。 无论是空心结构还是实心结 构, 机械探针 8清空喷嘴芯的速度为 1 ~ 200次 /min。
为使自内、外喷嘴芯出来的液流混合后沉淀生成的颗粒不发生或 少发生团聚, 在环形锥管收集器 11末端外置超声探头 13, 来对其捕 集到的悬浮液进行分散和抗团聚。
在其中的一个实施方案中, 参见图 2, 多个微通道套管式装置也 可以并联在一起, 以便于该装置在工业实施中, a液体和 b液体获 得相同的微观混合效果, 能够可靠地实现产品的工业化生产。
在其中的一个实施方案中,本发明中的 a液体和 b液体是混合后 发生反应产生沉淀的溶液。
其中, a液体可以是金属盐溶液, b液体为沉淀剂溶液。
金属盐溶液可以是金属的乙酸盐、 氯盐、硝酸盐、磷酸盐、硫酸 盐或碳酸盐, 或者上述多种金属盐的混合物。
沉淀剂溶液可以是碱溶液, 比如氢氧化钠、氢氧化钾或氢氧化铵 等无机碱溶液,或者四曱基氢氧化铵等有机碱溶液,或者上述多种碱 溶液的混合物。
在其中的一个更具体的实施方案中, a液体为 BaCl2和 TiCl4混 合溶液, b液体为 NaOH溶液。 其中 a液体中 Ba/Ti摩尔比为 1.05, Ti4+粒子在溶液 a 中浓度为 0.5 mol L。 b液体中 Off的浓度为 3.0 mol L。 a液体和 b液体进入各自进液管的体积流量比为 1:1,体积流 量均为 20L/h, 流速均为 2m/s。 反应温度通过控温夹套 6控制在 90 。 汇流于环形锥管收集器 11再流出的悬浮液经过滤、 干燥后得到 BaTi03纳米颗粒的粉体产品。 钛酸钡颗粒的粒径经 TEM 测试为 30±10腿。
在其中的一个实施方案中, a液体为药物溶液, b液体为反溶剂。 反溶剂溶液是指反溶剂溶液中的溶剂和药物溶液中的溶剂互溶, 但药物溶液在反溶剂溶液中的溶解度极低或几乎不溶。这样药物溶液 和反溶剂溶液混和后, 由于溶解度的变化, 会导致沉淀产生。
其中药物自以下描述的药物中选出: 镇痛药物, 消炎药物, 抗心 绞痛药物, 抗心律失常药物, 抗生素药物, 抗寄生虫药物, 抗凝血药 物, 抗抑郁药物, 抗糖尿病药物, 抗真菌药物, 抗组胺药物, 抗高血 压药物,抗毒蕈碱药物,抗赞疣药物,抗偏头痛药物,抗寄生物药物, 抗帕金森药物, 抗精神病药物, 催眠药, 镇静药, 抗中风药物, 抗血 栓药物, 抗咳嗽药物, 抗病毒药物, P -肾上腺素受体阻断剂, 钙离 子通道阻断剂, 血管收缩药, 避孕药, 皮质甾体, 皮肤科药物, 消毒 药物, 利尿剂, 胃肠道用药, 全麻药物, 止血剂, 局麻药, 阿片类镇 痛药, 拟副交感神经药物, 肽类, 性激素, 甾体, 诱导剂, 血管扩张 剂,一氧化氮制剂,制剂可用的酸、碱及盐衍生物, 空间异构衍生物。 在其中的一个实施方案中, 药物溶液 a中的药物选自于: 菲洛贝 特, 头孢呋辛酯, 阿奇審素, 洛匹那韦, 环孢審素, 醋酸曱地孕酮, 比卡鲁胺, 左旋多巴, 环丙沙星, 喜树碱, 达那唑, 奈普生, 水飞蓟 宾, 伊曲康唑。
在其中的一个实施方案中, 药物溶液 a中的溶剂是曱醇、 乙醇、 丙酮、 正丙醇、 异丙醇或上述溶剂的混和物中的一种。
在其中的一个实施方案中, 反溶剂溶液中的反溶剂是水。
在其中的一个实施方案中, 药物溶液3、反溶剂溶液 b或经过微 通道套管式微观混和与反应装置后形成沉淀后的悬浮液中至少添加 一种或一种以上助剂。
在其中的一个实施方案中, 添加于溶液药物溶液 a、 反溶剂溶液 b或经过微通道套管式微观混和与反应装置后形成沉淀后的悬浮液 中的助剂, 自填充剂 (稀释剂)、 黏合剂、 润滑剂和崩解剂等助剂中 选出。
在其中的一个实施方案中, 添加于溶液药物溶液 a、 反溶剂溶液 b或经过微通道套管式微观混和与反应装置后形成沉淀后的悬浮液 中的助剂, 自乳糖、 微晶纤维素、 甘露醇、 糊精、 羟丙曱纤维素、 聚 维酮、胶联羧曱基纤维素钠、胶联聚维酮、 聚乙烯醇、 十二烷基硫酸 镁和十二烷^ ¾酸钠等中选出。
在其中一个更具体的实施方案中,药物溶液 a通过将 20g菲洛贝 特和 0.5g十二烷基硫酸钠溶解于 200ml乙醇中形成, 在进入进液管 I ( 2 )之前, 药物溶液 a的温度控制在 35 °C。 反溶剂溶液 b通过 将 76g乳糖、 2g羟丙曱纤维素 -E3和 1.5g十二烷基硫酸钠溶于 2L水 中, 在进入进液管 II ( 3 )之前, 反溶剂溶液 b的温度控制在 4 °C。 药物溶液 a和反溶剂溶液 b进入各自进液管的流量比为 1:10。 菲洛 贝特溶液进入进液管 I ( 2 ) 的流量为 2L/hr。 菲洛贝特溶液进入进 液管 I ( 2 ) 的流速为 lm/s。 两股液流经喷嘴芯(9, 10 )微观混和 后, 汇流于环形锥管收集器(11 )再流出的悬浮液在线经喷雾干燥器 干燥得到含有纳米菲洛贝特颗粒和助剂的的粉体。粉体中菲洛贝特颗 粒大小 SEM测试为 300±100nm。该粉体中菲洛贝特颗粒很好地分散 于助剂中。最终的菲洛贝特粉体可以用于制剂、改善菲洛贝特制剂后 的生物利用度。

Claims

权 利 要 求
1、 一种微通道套管式装置, 包括内喷嘴通道(4)、 外喷嘴通道 (5)和机械探针(8), 其中外喷嘴通道(5)基本同心地环绕内喷嘴 通道(4), 内喷嘴通道(4)基本同心地环绕机械探针(8), 内喷嘴 通道( 4 )在其出口部收缩后延伸形成内喷嘴芯( 9 ), 外喷嘴通道( 5 ) 在其出口部收缩后延伸形成外喷嘴芯(10), 外喷嘴芯 (10)基本同 心地环绕内喷嘴芯 (9), 机械探针 (8)经配置能够间歇地清空内喷 嘴芯(9)。
2、根据权利要求 1的微通道套管式装置, 其中机械探针(8)是 空心结构以允许高压气体间歇地通过机械探针 (8)进入并清空内喷 嘴芯(9)。
3、根据权利要求 1的微通道套管式装置, 其中机械探针(8)是 实心结构, 经配置能够间歇地进入并清空内喷嘴芯 (9)。
4、 根据权利要求 1~3中任意一项的微通道套管式装置, 其中机 械探针 (8)清空内喷嘴芯 (9) 的频率是 1~200次 /分钟。
5、 根据权利要求 1~4中任意一项的微通道套管式装置, 还包括 环绕在外喷嘴通道(5)周围的控温夹套(6)。
6、根据权利要求 1 ~ 5中任意一项的微通道套管式装置,还包括 环绕在外喷嘴芯 (10) 的出口和内喷嘴芯 (9) 的出口周围的收集器
(11 )。
7、根据权利要求 1 ~ 6中任意一项的微通道套管式装置,还包括 设置在收集器( 11 )末端外置的超声探头以在收集器( 11 )中避免颗 粒的凝并和 /或分散已形成的颗粒团聚体。
8、根据权利要求 1 ~ 7中任意一项的微通道套管式装置,其中所 述内喷嘴芯 (9) 的通道为圆形孔、 正方形孔或正三角形孔, 内喷嘴 芯(9)通道孔的直径或边长为 0.01 ~ 5mm, 外喷嘴芯(10)环绕内 喷嘴芯 (9)的间隙尺寸为 0.01 ~5mm。
9、根据权利要求 1 ~ 8中任意一项的微通道套管式装置,其中通 过所述内喷嘴芯 (9)和外喷嘴芯 (10) 出口处的两股流体各自独立 地具有 0.01 ~ 50m/s的流速, 0.01 ~ 500 L/min的体积流量,和 1000 ~ 100000雷诺数。
10、一种微通道套管式装置,其特征是,由多个根据权利要求 1 ~ 9中任意一项的所述微通道套管式装置并联在一起组成。
11、根据权利要求 1 ~ 10中任意一项的所述微通道套管式装置在 利用液-液体系制备具有纳、微米结构的无机、有机或药物颗粒中的 用途。
12、 根据权利要求 11的所述微通道套管式装置的用途, 其中采 用液-液沉淀法制备金属氧化物纳米颗粒,将金属离子盐溶液通入内 喷嘴通道(4 ), 将沉淀剂溶液通入外喷嘴通道(5 ), 金属离子盐溶液 和沉淀剂溶液在离开内喷嘴芯 (9 ) 出口和外喷嘴芯 (10 ) 出口后混 合、反应形成悬浮液, 以及任选地, 该悬浮液经干燥后得到金属氧化 物纳米颗粒的粉体产品。
13、 根据权利要求 11的所述微通道套管式装置的用途, 其中采 用液-液沉淀法制备药物颗粒,将溶解有药物的药物溶液通入内喷嘴 通道( 4 ),将含有与药物溶液互溶的反溶剂溶液通入外喷嘴通道( 5 ), 药物溶液和反溶剂溶液在离开内喷嘴芯 (9 ) 出口和外喷嘴芯 (10 ) 出口后混合、沉淀形成悬浮液, 以及任选地, 该悬浮液干燥后得到药 物颗粒的粉体产品。
14、根据权利要求 12或 13的所述微通道套管式装置的用途,其 中在所述悬浮液中添加一种或多种助剂。
15、根据权利要求 12或 13的所述微通道套管式装置的用途,其 中所述干燥是在线喷雾干燥或在线冷冻干燥。
16、 根据权利要求 13的所述微通道套管式装置的用途, 其中所 述药物选自:镇痛药物, 消炎药物,抗心绞痛药物,抗心律失常药物, 抗生素药物, 抗寄生虫药物, 抗凝血药物, 抗抑郁药物, 抗糖尿病药 物, 抗真菌药物, 抗组胺药物, 抗高血压药物, 抗毒蕈碱药物, 抗赘 疣药物, 抗偏头痛药物, 抗寄生物药物, 抗帕金森药物, 抗精神病药 物, 催眠药, 镇静药, 抗中风药物, 抗血栓药物, 抗咳散药物, 抗病 毒药物, p -肾上腺素受体阻断剂, 钙离子通道阻断剂, 血管收缩药, 避孕药, 皮质甾体, 皮肤科药物, 消毒药物, 利尿剂, 胃肠道用药, 全麻药物, 止血剂, 局麻药, 阿片类镇痛药, 拟副交感神经药物, 肽 类, 性激素, 甾体, 诱导剂, 血管扩张剂, 一氧化氮制剂, 制剂可用 的酸、 碱及盐衍生物, 空间异构衍生物。
17、根据权利要求 13或 16的所述微通道套管式装置的用途,其 中所述药物选自: 菲洛贝特, 头孢呋辛酯, 阿奇審素, 洛匹那韦, 环 孢審素, 比卡鲁胺, 醋酸曱地孕酮, 左旋多巴, 环丙沙星, 喜树碱, 达那唑, 奈普生, 水飞蓟宾, 伊曲康唑和罗红審素。
18、 根据权利要求 14的所述微通道套管式装置的用途, 其中所 述助剂选自: 填充剂、 稀释剂、 黏合剂、 润滑剂和崩解剂。
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