A supercritical carbon dioxide process equipment for preparing α / β mixed crystal porous lactose microparticles and a preparation method thereof

Abstract

The present invention relates to a supercritical carbon dioxide process equipment for preparing α / β mixed crystal porous lactose particles, comprising a supercritical fluid preparation unit, an atomization unit, a collection unit, a vibrating screen and a control unit; the supercritical fluid preparation unit is used for heating carbon dioxide to a supercritical temperature and pressurizing it to a supercritical pressure, and the supercritical fluid preparation unit includes a heater, a high-pressure pump, a pressure regulating valve and a flow meter; the atomization unit is used for mixing the heated carbon dioxide with a lactose solution and spraying it to form a mist, and the atomization unit includes a nozzle, a mixing chamber and a lactose solution heater; the collection unit is used for collecting and cooling the sprayed mist to generate α / β mixed crystal porous lactose particles, and the collection unit includes a collection cylinder and a cooling device; the vibrating screen is used for sorting the generated lactose particles, and the vibrating screen includes a screen body and a screen mesh; the control unit includes a temperature and pressure sensor and a controller. The technical solution of the present application can reliably prepare α / β mixed crystal porous lactose particles.

Description

Technical Field

[0001] The present invention relates to the field of preparing α / β mixed crystal porous lactose particles, and in particular to an apparatus and method for preparing α / β mixed crystal porous lactose particles using supercritical fluid technology. Background Art

[0002] Lactose is an important natural polysaccharide and is widely used in the fields of pharmaceuticals, food, and cosmetics. Lactose particles have good moisture retention, stability, and adsorption properties, and are thus widely used in fields such as skin care, drug delivery, and the preparation of nanomaterials.

[0003] Furthermore, α-lactose and β-lactose are two isomers with very similar chemical structures but different molecular configurations. Specifically, the difference between them lies in the positions of their hydroxyl groups. When preparing α / β lactose composite particles, due to the limitations of traditional preparation methods, the quality of the product is usually affected by environmental pollution, and at the same time, the degradability and drug delivery performance of the composite particles also need to be improved. Summary of the Invention

[0004] To solve the above technical problems, the object of the present invention is to provide a supercritical carbon dioxide process apparatus for preparing α / β mixed crystal porous lactose particles:

[0005] Comprising a supercritical fluid preparation unit, an atomization unit, a collection unit, a vibrating screen, and a control unit;

[0006] The supercritical fluid preparation unit is used to heat carbon dioxide to supercritical temperature and pressurize it to supercritical pressure. The supercritical fluid preparation unit includes: a heater, a high-pressure pump, a pressure regulating valve, and a flow meter;

[0007] The atomization unit is used to mix the heated carbon dioxide with a lactose solution and spray it out to form a mist. The atomization unit includes a nozzle, a mixing chamber, and a lactose solution heater;

[0008] The collection unit is used to collect and cool the sprayed mist to generate α / β mixed crystal porous lactose particles. The collection unit includes a collection cylinder and a cooling device;

[0009] The vibrating screen is used to sort the generated lactose particles. The vibrating screen includes a screen body and a screen mesh;

[0010] The control unit is used to monitor and adjust the temperature, pressure, and nozzle outlet velocity of the supercritical fluid preparation unit and the atomization unit in real time. The control unit includes a temperature and pressure sensor and a controller.

[0011] Preferably, the heater of the supercritical fluid preparation unit has an operating temperature range of 30 to 100 °C, and the high-pressure pump has an operating pressure range of 7.38 to 30 MPa. The supercritical fluid preparation unit further includes a carbon dioxide storage tank and an interface connector that cooperate with the heater, the high-pressure pump, the pressure regulating valve, and the flow meter.

[0012] Preferably, the nozzle of the atomization unit has an outlet velocity range of 0.1 to 10 m / s, and the spray droplet size range is 1 to 100 μm. The atomization unit further includes a lactose solution delivery pump and a lactose solution storage tank that cooperate with the nozzle, the mixing chamber, and the lactose solution heater.

[0013] Preferably, the cooling device of the collection unit uses a refrigerant circulation system. The collection unit further includes a gas recovery device and a collection base that cooperate with the collection cylinder and the cooling device. The collection cylinder is a porous lactose particle collection device.

[0014] Preferably, the vibrating screen has a screen body with an adjustable vibration frequency, and the screen mesh is a multi-layer screen mesh structure. The vibrating screen further includes a screen mesh fixing frame and a screening base that cooperate with the screen body and the screen mesh.

[0015] Preferably, the control unit has a programmable logic controller (PLC) and a human-machine interface (HMI), which are used to monitor and adjust the temperature and pressure of supercritical carbon dioxide, the outlet velocity of the nozzle, and the vibration frequency of the vibrating screen in real time. The control unit further includes a display screen, operation buttons, and a housing.

[0016] A method for preparing α / β mixed crystal porous lactose particles includes the following steps:

[0017] a: Feed supercritical carbon dioxide into the supercritical fluid preparation unit and adjust the temperature and pressure to the required range;

[0018] b: Spray the lactose solution into the atomization unit to form a mist, and mix it with the supercritical carbon dioxide in the supercritical fluid preparation unit 1;

[0019] c: Feed the mixed mist into the collection unit and collect and cool it through the collection cylinder and the cooling device;

[0020] d: Feed the collected porous lactose particles into the vibrating screen for separation and collection;

[0021] e: Monitor and adjust the process parameters in real time through the control unit to achieve the preparation of α / β mixed crystal porous lactose particles with different ratios.

[0022] Preferably, in step a, the temperature range of the supercritical carbon dioxide is 30 to 100 °C, and the pressure range is 7.38 to 30 MPa.

[0023] Preferably, in step b, the outlet velocity range of the nozzle is 0.1 - 10 m / s, and the spray droplet size range is 1 - 100 μm.

[0024] By means of the above solution, the present invention has at least the following advantages:

[0025] In the technical solution of the present invention, by spraying a lactose solution into the atomization unit and mixing it with supercritical carbon dioxide to form a mixed mist, and then collecting and cooling it through the collection unit, α / β mixed crystal porous lactose microparticles are finally obtained;

[0026] At the same time, by controlling process parameters such as the temperature and pressure of supercritical carbon dioxide, the size of the spray droplets, and the outlet velocity of the nozzle, the preparation of α / β mixed crystal porous lactose microparticles with different ratios can be achieved;

[0027] And the supercritical fluid technology is a widely used green chemical technology, which has high solvent capacity, controllability, and selectivity. Under the action of supercritical fluids, particulate materials with special properties can be prepared, such as those with porous structures, high specific surface areas, and special crystal forms, etc.;

[0028] The present invention mainly relates to fields such as supercritical fluid technology, nanomaterial preparation, lactose microparticle preparation, and biomedical materials. The supercritical fluid technology is a widely used green chemical technology and has broad application prospects in fields such as nanomaterial preparation, drug delivery, and catalysts;

[0029] And the preparation of nanomaterials has been one of the research hotspots in recent years. Lactose microparticles are an important type of nanomaterial, which have special properties such as porous structures, high specific surface areas, and special crystal forms, and are widely used in fields such as skin care, drug delivery, and nanomaterial preparation. The preparation of lactose microparticles is an important branch in the field of lactose research. By preparing lactose microparticles with different morphologies, sizes, and structures, new products such as drug delivery systems, antibacterial agents, and chewing gums can be developed. Biomedical materials are an important research field with broad application prospects. As a biomedical material, lactose microparticles have good biocompatibility and biodegradability and can be used in applications such as drug delivery systems and tissue engineering materials.

[0030] The technical solution of the present invention provides a method for preparing α / β mixed crystal porous lactose microparticles. Through devices such as a supercritical fluid preparation unit, an atomization unit, a collection unit, and a vibrating screen, the mixing of a lactose solution and supercritical carbon dioxide to form a mist is realized, and porous lactose microparticles are formed under the action of a collector and a cooling device; and by real-time monitoring and adjustment of process parameters, α / β mixed crystal porous lactose microparticles with different ratios can also be prepared.

[0031] The function of real-time monitoring and adjusting process parameters is to ensure the quality and performance of porous lactose microparticles, such as particle size, porosity, crystal form, etc. The size distribution, morphology, structure, etc. of lactose microparticles can be detected by an online dust particle counter or other instruments, and parameters such as the concentration, temperature, pH value, spraying rate, etc. of the lactose solution can be adjusted according to the real-time data. This can improve production efficiency and quality consistency, and reduce costs and risks.

[0032] Real-time monitoring and adjusting process parameters is to ensure the quality and performance of porous lactose microparticles, such as particle size, porosity, crystal form, etc., and an online dust particle counter or other instruments can detect the size distribution, morphology, structure, etc. of lactose microparticles, and adjust parameters such as the concentration, temperature, pH value, spraying rate, etc. of the lactose solution according to the real-time data. This can improve production efficiency and quality consistency, and reduce costs and risks.

[0033] The technical solution of this application includes a supercritical fluid preparation unit, an atomization unit, a collection unit, a vibrating screen and a control unit.

[0034] The heater in the supercritical fluid preparation unit heats carbon dioxide to the supercritical temperature and pressurizes it to the supercritical pressure through a high-pressure pump. The pressure regulating valve and flowmeter are used to regulate and measure the pressure and flow rate of carbon dioxide. Supercritical carbon dioxide acts as a solvent and reaction medium in this process.

[0035] The nozzle in the atomization unit mixes the heated carbon dioxide with the lactose solution and sprays it out to form a mist. The outlet velocity of the nozzle and the size of the spray droplets can be adjusted and controlled.

[0036] The collection unit is used to collect and cool the sprayed mist to generate α / β mixed crystal porous lactose microparticles. The porous lactose microparticle collector and the cooling device are used to collect and cool the mist.

[0037] The vibrating screen is used to sort and collect the generated lactose microparticles. The vibration frequency of the screen body and the multi-layer structure of the screen mesh help to effectively separate the microparticles.

[0038] The control unit real-time monitors and adjusts the temperature, pressure and nozzle outlet velocity of the supercritical fluid preparation unit and the atomization unit. It uses temperature and pressure sensors and controllers to monitor and adjust parameters to achieve precise control of the preparation process.

[0039] The technical solution of the present application has the following advantages: Using supercritical carbon dioxide as a solvent avoids the environmental pollution and the impact on product quality caused by the commonly used organic solvents in traditional methods; By means of atomization and deposition, porous lactose microparticles can be prepared, which can have a porous structure and a high specific surface area, improving their biodegradability and drug delivery performance; By real-time monitoring and adjusting process parameters, the preparation of α / β mixed crystal porous lactose microparticles with different ratios can be realized, improving the controllability and stability of the product. Therefore, the method provided by the invention has the advantages of simple preparation, environmental friendliness, stable product quality and broad application prospects

[0040] The above description is only an overview of the technical solution of the present invention. In order to be able to understand the technical means of the present invention more clearly and to be implemented in accordance with the content of the description, the following takes the preferred embodiments of the present invention and combines the attached drawings to elaborate in detail as follows Brief Description of the Drawings

[0041] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required to be used in the embodiments. It should be understood that the following drawings only show a certain embodiment of the present invention, so it should not be regarded as a limitation of the scope. For those of ordinary skill in the art, without creative efforts, other related drawings can also be obtained based on these drawings

[0042] Figure 1 It is a schematic structural diagram of the device for preparing α / β mixed crystal porous lactose microparticles of the present invention

[0043] Figure 2 It is an electron micrograph of the α / β mixed crystal porous lactose microparticles prepared in the first embodiment of the present invention

[0044] Figure 3 It is an electron micrograph of the α / β mixed crystal porous lactose microparticles prepared in the first embodiment of the present invention

[0045] Figure 4 It is an electron micrograph of the α / β mixed crystal porous lactose microparticles prepared in the second embodiment of the present invention

[0046] Figure 5 It is an electron micrograph of the α / β mixed crystal porous lactose microparticles prepared in the second embodiment of the present invention

[0047] Figure 6 It is an electron micrograph of the α / β mixed crystal porous lactose microparticles prepared in the third embodiment of the present invention

[0048] Figure 7 It is an electron micrograph of the α / β mixed crystal porous lactose microparticles prepared in the third embodiment of the present invention Detailed Description of the Embodiments

[0049] The following further describes in detail the specific implementation manners of the present invention in conjunction with the accompanying drawings and embodiments. The following embodiments are used to illustrate the present invention, but are not used to limit the scope of the present invention.

[0050] A supercritical carbon dioxide process equipment for preparing α / β mixed crystal porous lactose particles according to a preferred embodiment of the present invention:

[0051] It includes a supercritical fluid preparation unit 1, an atomization unit 2, a collection unit 3, a vibrating screen 4 and a control unit 5;

[0052] The supercritical fluid preparation unit 1 is used to heat carbon dioxide to the supercritical temperature and pressurize it to the supercritical pressure. The supercritical fluid preparation unit 1 includes: a heater 1-1, a high-pressure pump 1-2, a pressure regulating valve 1-3 and a flowmeter 1-4;

[0053] The atomization unit 2 is used to mix the heated carbon dioxide with the lactose solution and spray it to form a mist. The atomization unit 2 includes a nozzle 2-1, a mixing chamber 2-2 and a lactose solution heater 2-3;

[0054] The collection unit 3 is used to collect and cool the sprayed mist to generate α / β mixed crystal porous lactose particles. The collection unit 3 includes a collection cylinder 3-1 and a cooling device 3-2;

[0055] The vibrating screen 4 is used to sort the generated lactose particles. The vibrating screen 4 includes a screen body 4-1 and a screen mesh 4-2;

[0056] The control unit 5 is used to monitor and adjust in real time the temperature, pressure and the outlet speed of the nozzle 2-1 of the supercritical fluid preparation unit 1 and the atomization unit 2. The control unit 5 includes temperature and pressure sensors 5-1, 5-2 and a controller 5-3.

[0057] Preferably, the working temperature range of the heater 1-1 of the supercritical fluid preparation unit 1 is 30 to 100 °C, the working pressure range of the high-pressure pump 1-2 is 7.38 to 30 MPa. The supercritical fluid preparation unit 1 further includes a carbon dioxide storage tank 1-5 and an interface connector 1-6 that cooperate with the heater 1-1, the high-pressure pump 1-2, the pressure regulating valve 1-3 and the flowmeter 1-4.

[0058] Preferably, the outlet speed range of the nozzle 2-1 of the atomization unit 2 is 0.1 to 10 m / s, the spray droplet size range is 1 to 100 μm. The atomization unit 2 further includes a lactose solution delivery pump 2-4 and a lactose solution storage tank 2-5 that cooperate with the nozzle 2-1, the mixing chamber 2-2 and the lactose solution heater 2-3.

[0059] Preferably, the cooling device 3-2 of the collection unit 3 adopts a refrigerant circulation system. The collection unit 3 further includes a gas recovery device 3-3 and a collection base 3-4 that cooperate with the collection cylinder 3-1 and the cooling device 3-2. The collection cylinder 3-1 is a porous lactose particle collection device.

[0060] Preferably, the sieve body 4-1 of the vibrating screen 4 has an adjustable vibration frequency, and the sieve mesh 4-2 has a multi-layer sieve mesh structure. The vibrating screen 4 further includes a sieve mesh fixing frame 4-3 and a screening base 4-4 that cooperate with the sieve body 4-1 and the sieve mesh 4-2.

[0061] The vibrating screen 4 adopts a multi-layer sieve mesh structure and an adjustable vibration frequency to achieve the separation and collection of porous lactose particles of different sizes.

[0062] Preferably, the control unit 5 has a programmable logic controller PLC and a human-machine interface HMI, which are used to monitor and adjust the temperature, pressure of supercritical carbon dioxide, the outlet speed of the nozzle 2-1, and the vibration frequency of the vibrating screen 4 in real time. The control unit 5 further includes a display screen 5-4, operation buttons 5-5, and a housing 5-6.

[0063] The control unit 5 can monitor and adjust process parameters such as nozzle diameter, feeding rate, and inlet temperature in real time, or control process parameters such as air intake volume and outlet temperature, (the technical parameters of spray drying also affect the properties of the particles, such as nozzle diameter, feeding rate, air intake volume, inlet temperature, and outlet temperature. Generally speaking, increasing the nozzle diameter, feeding rate, and inlet temperature, or decreasing the air intake volume and outlet temperature, will increase the average particle size of the particles. Specific parameter settings need to be optimized according to the actual situation.) to achieve the preparation of α / β mixed crystal porous lactose particles in different proportions

[0064] A method for preparing α / β mixed crystal porous lactose particles includes the following steps:

[0065] a: Feed supercritical carbon dioxide into the supercritical fluid preparation unit 1 and adjust the temperature and pressure to the required range;

[0066] b: Spray the lactose solution into the atomization unit 2 to form a mist, and mix it with the supercritical carbon dioxide in the supercritical fluid preparation unit (1);

[0067] c: Feed the mixed mist into the collection unit 3 and collect and cool it through the collection cylinder 3-1 and the cooling device 3-2;

[0068] d: Feed the collected porous lactose particles into the vibrating screen 4 for separation and collection;

[0069] e: Monitor and adjust the process parameters in real time through the control unit 5 to achieve the preparation of α / β mixed crystal porous lactose particles in different proportions.

[0070] Preferably, in step a, the temperature range of the supercritical carbon dioxide is 30 to 100 °C, and the pressure range is 7.38 to 30 MPa.

[0071] Preferably, in step b, the outlet velocity range of the nozzle 2-1 is 0.1 to 10 m / s, and the spray droplet size range is 1 to 100 μm.

[0072] Example 1:

[0073] Refer to Figure 2 and Figure 3 , feed the supercritical carbon dioxide into the supercritical fluid preparation unit 1, adjust the temperature and pressure, the temperature range of the supercritical carbon dioxide is 30 °C, and the pressure range is 7.38 MPa;

[0074] Spray the lactose solution into the atomization unit to form a mist, and mix it with the supercritical carbon dioxide in the supercritical fluid preparation unit 1. The outlet velocity of the nozzle 2-1 is 0.1 m / s, and the spray droplet size range is 1 μm;

[0075] Feed the mixed mist into the collection unit 3, and collect and cool it through the porous lactose microparticle collector 3-1 and the cooling device 3-2;

[0076] Feed the collected porous lactose microparticles into the vibrating screen 4 for separation and collection;

[0077] Example 1 can achieve the preparation of α / β mixed crystal porous lactose microparticles with a ratio of 9:1.

[0078] Example 2:

[0079] Refer to Figure 4 and Figure 5 , feed the supercritical carbon dioxide into the supercritical fluid preparation unit 1, adjust the temperature and pressure, the temperature range of the supercritical carbon dioxide is 65 °C, and the pressure range is 18.69 MPa;

[0080] Spray the lactose solution into the atomization unit to form a mist, and mix it with the supercritical carbon dioxide in the supercritical fluid preparation unit 1. The outlet velocity of the nozzle 2-1 is 5.05 m / s, and the spray droplet size range is 50.5 μm;

[0081] Feed the mixed mist into the collection unit 3, and collect and cool it through the porous lactose microparticle collector 3-1 and the cooling device 3-2;

[0082] Feed the collected porous lactose microparticles into the vibrating screen 4 for separation and collection;

[0083] Example 2 can achieve the preparation of α / β mixed crystal porous lactose microparticles with a ratio of 7:3.

[0084] Example 3:

[0085] Refer to Figure 6 and Figure 7 , feed supercritical carbon dioxide into the supercritical fluid preparation unit 1, adjust the temperature and pressure, the temperature range of the supercritical carbon dioxide is 100 °C, and the pressure range is 30 MPa;

[0086] Spray the lactose solution into the atomization unit to form a mist, and mix it with the supercritical carbon dioxide in the supercritical fluid preparation unit 1. The outlet speed of the nozzle 2-1 is 10 m / s, and the spray droplet size range is 100 μm;

[0087] Feed the mixed mist into the collection unit 3, and collect and cool it through the porous lactose particle collector 3-1 and the cooling device 3-2;

[0088] Feed the collected porous lactose particles into the vibrating screen 4 for separation and collection;

[0089] Example 3 can achieve the preparation of α / β mixed crystal porous lactose particles with a ratio of 9:1.

[0090] Furthermore, lactose is a disaccharide composed of one molecule of galactose and one molecule of glucose linked by a β-1,4-glycosidic bond. Lactose has two configurations, α-lactose and β-lactose, and their difference lies in whether the hemiacetal hydroxyl group of the galactose part and the terminal hydroxymethyl group of the glucose part are on the same side or the opposite side of the ring plane 1. The solubility of α-lactose and β-lactose in water also varies with temperature. When α-lactose dissolves in water, it gradually turns into the β-form. Since β-lactose is more soluble in water than α-lactose, the initial solubility of lactose is not stable but gradually increases until the α-form and β-form reach equilibrium 2.

[0091] The technical solution of this application uses supercritical carbon dioxide process equipment to prepare α / β mixed crystal porous lactose particles. Supercritical carbon dioxide is a fluid with characteristics such as high density, low viscosity, high diffusion coefficient, and low surface tension. In the supercritical state, it can be used as a solvent or carrier to process various substances. The supercritical carbon dioxide process equipment mainly includes parts such as a supercritical fluid preparation unit, an atomization unit, a collection unit, and a vibrating screen. The supercritical fluid preparation unit is used to heat carbon dioxide to the supercritical temperature and pressurize it to the supercritical pressure; the atomization unit is used to mix the heated carbon dioxide with the lactose solution and spray it to form a mist; the collection unit is used to collect and cool the sprayed mist to generate α / β mixed crystal porous lactose particles; the vibrating screen is used to sort the generated lactose particles.

[0092] The main factors affecting the ratio of α / β mixed crystal porous lactose particles are as follows:

[0093] Temperature and pressure of carbon dioxide: These two parameters determine the density and solubility of carbon dioxide, as well as its influence on the transformation between α / β configurations in the lactose solution. Generally speaking, the higher the temperature and the lower the pressure, the closer carbon dioxide is to the gaseous state and the weaker its solubility; the lower the temperature and the higher the pressure, the closer carbon dioxide is to the liquid state and the stronger its solubility. At the same time, temperature and pressure also affect the equilibrium of α / β configurations in the lactose solution, and may promote or inhibit the transformation from α-form to β-form. Therefore, under different temperature and pressure conditions, porous lactose microparticles with different proportions of α / β mixed crystals may be obtained.

[0094] Outlet velocity of the nozzle and size of the spray droplets: These two parameters determine the mixing degree and contact time between the lactose solution and carbon dioxide in the atomization unit, as well as the cooling rate of the ejected mist. Generally speaking, the higher the outlet velocity and the larger the size of the spray droplets, the lower the mixing degree between the lactose solution and carbon dioxide and the shorter the contact time; the lower the outlet velocity and the smaller the size of the spray droplets, the higher the mixing degree between the lactose solution and carbon dioxide and the longer the contact time. At the same time, the outlet velocity and the size of the spray droplets also affect the cooling rate of the ejected mist, and may affect the fixation or transformation of α / β configurations in the lactose solution. Therefore, under different outlet velocities and sizes of spray droplets, porous lactose microparticles with different proportions of α / β mixed crystals may be obtained.

[0095] Surface coating of the collection unit and cooling device: These two parameters determine the collection efficiency and cooling effect of the porous lactose microparticles in the collection unit, as well as their influence on the structure and properties of the porous lactose microparticles. Generally speaking, the smoother the surface coating and the more powerful the cooling device, the higher the collection efficiency of the porous lactose microparticles and the better the cooling effect; the rougher the surface coating and the weaker the cooling device, the lower the collection efficiency of the porous lactose microparticles and the worse the cooling effect. At the same time, the surface coating and the cooling device also affect the structure and properties of the porous lactose microparticles, and may cause adhesion or fusion between the porous lactose microparticles or with the collector, or change the stability of α / β configurations in the porous lactose microparticles. Therefore, under different surface coatings and cooling devices, porous lactose microparticles with different proportions of α / β mixed crystals may be obtained.

[0096] In summary, in the above three embodiments:

[0097] In Example 1, the lowest temperature, pressure, outlet velocity and size of the spray droplets were used, which may result in the weakest solubility of carbon dioxide in the lactose solution, the lowest mixing degree between the lactose solution and carbon dioxide, the shortest contact time, and the slowest cooling rate of the ejected mist. This means that under such conditions, the chance of transformation between α / β configurations in the lactose solution is the smallest, and it is not easy to change when fixed in the porous lactose microparticles.

[0098] In Example 2, medium temperature, pressure, outlet velocity, and spray droplet size conditions were used, which resulted in a relatively strong dissolution ability of carbon dioxide in the lactose solution, a relatively high degree of mixing between the lactose solution and carbon dioxide, a relatively long contact time, and a relatively fast cooling rate of the ejected mist. This may mean that under such conditions, there is a relatively high chance of transformation between the α / β configurations in the lactose solution, and it is also prone to change when fixed in the porous lactose microparticles.

[0099] In Example 3, the highest temperature, pressure, outlet velocity, and spray droplet size conditions were used, which resulted in the strongest dissolution ability of carbon dioxide in the lactose solution, the highest degree of mixing between the lactose solution and carbon dioxide, the longest contact time, and the fastest cooling rate of the ejected mist. This may mean that under such conditions, there is the highest chance of transformation between the α / β configurations in the lactose solution, and it is also most prone to change when fixed in the porous lactose microparticles.

[0100] Therefore, the proportion of α / β mixed crystal porous lactose microparticles obtained in Example 1 is most likely to be close to the proportion in the original lactose solution. The proportion of α / β mixed crystal porous lactose microparticles obtained in Example 2 has a certain degree of change, and the proportion of α / β mixed crystal porous lactose microparticles obtained in Example 3 has a large degree of change.

[0101] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. It should be noted that for those of ordinary skill in the art, without departing from the technical principle of the present invention, several improvements and modifications can be made, and these improvements and modifications should also be regarded as the protection scope of the present invention.

Claims

1. A method for preparing α / β mixed crystal porous lactose microparticles using a supercritical carbon dioxide device, characterized in that, The specific preparation steps are as follows: a: Feed supercritical carbon dioxide into the supercritical fluid preparation unit (1), and adjust the temperature and pressure to the required range; b: Spray the lactose solution into the atomization unit (2) to form a mist, and mix it with the supercritical carbon dioxide in the supercritical fluid preparation unit (1); c: Feed the mixed mist into the collection unit (3), and collect and cool it through the collection cylinder (3-1) and the cooling device (3-2); d: Feed the collected porous lactose particles into the vibrating screen (4) for separation and collection; e: Real-time monitor and adjust the process parameters through the control unit (5) to achieve the preparation of α / β mixed crystal porous lactose particles with different ratios; The supercritical carbon dioxide equipment includes a supercritical fluid preparation unit (1), an atomization unit (2), a collection unit (3), a vibrating screen (4) and a control unit (5); The supercritical fluid preparation unit (1) is used to heat carbon dioxide to the supercritical temperature and pressurize it to the supercritical pressure. The supercritical fluid preparation unit (1) includes: a heater (1-1), a high-pressure pump (1-2), a pressure regulating valve (1-3) and a flow meter (1-4); The atomization unit (2) is used to mix the heated carbon dioxide with the lactose solution and spray it to form a mist. The atomization unit (2) includes a nozzle (2-1), a mixing chamber (2-2) and a lactose solution heater (2-3); The collection unit (3) is used to collect and cool the sprayed mist to generate α / β mixed crystal porous lactose particles. The collection unit (3) includes a collection cylinder (3-1) and a cooling device (3-2); The vibrating screen (4) is used to sort the generated lactose particles. The vibrating screen (4) includes a screen body (4-1) and a screen mesh (4-2); The control unit (5) is used to real-time monitor and adjust the temperature, pressure of the supercritical fluid preparation unit (1) and the atomization unit (2), and the outlet speed of the nozzle (2-1). The control unit (5) includes temperature and pressure sensors (5-1, 5-2), a controller (5-3); The working temperature range of the heater (1-1) in the supercritical fluid preparation unit (1) is 30-100°C, and the working pressure range of the high-pressure pump (1-2) is 7.38-30 MPa. The supercritical fluid preparation unit (1) also includes a carbon dioxide storage tank (1-5) and an interface connector (1-6) that cooperate with the heater (1-1), the high-pressure pump (1-2), the pressure regulating valve (1-3) and the flow meter (1-4); The outlet speed range of the nozzle (2-1) in the atomization unit (2) is 0.1-10 m / s, and the spray droplet size range is 1-100 μm. The atomization unit (2) also includes a lactose solution delivery pump (2-4) and a lactose solution storage tank (2-5) that cooperate with the nozzle (2-1), the mixing chamber (2-2) and the lactose solution heater (2-3).

2. The method for preparing α / β mixed crystal porous lactose particles by using a supercritical carbon dioxide device according to claim 1, wherein: The collection unit (3) is equipped with a cooling device (3-2) that adopts a refrigerant circulation system. The collection unit (3) also includes a gas recovery device (3-3) and a collection base (3-4) that cooperate with the collection cylinder (3-1) and the cooling device (3-2). The collection cylinder (3-1) is a porous lactose particle collection device.

3. A method for preparing α / β mixed crystalline porous lactose microparticles using a supercritical carbon dioxide apparatus according to claim 1, characterized in that: The vibrating screen (4) has a screen body (4-1) with an adjustable vibration frequency, and the screen mesh (4-2) is a multi-layer screen mesh structure. The vibrating screen (4) also includes a screen mesh fixing frame (4-3) and a screening base (4-4) that cooperate with the screen body (4-1) and the screen mesh (4-2).

4. A method for preparing α / β mixed crystal porous lactose particles using a supercritical carbon dioxide device according to claim 1, characterized in that: The control unit (5) has a programmable logic controller (PLC) and a human-machine interface (HMI), which are used to monitor and adjust the temperature and pressure of supercritical carbon dioxide, the outlet velocity of the nozzle (2-1), and the vibration frequency of the vibrating screen (4) in real time. The control unit (5) also includes a display screen (5-4), operation buttons (5-5), and a housing (5-6).

5. A method for preparing α / β mixed crystal porous lactose microparticles using a supercritical carbon dioxide device according to claim 1, characterized in that: In step a, the temperature range of supercritical carbon dioxide is 30 to 100 °C, and the pressure range is 7.38 to 30 MPa.

6. A method for preparing α / β mixed crystal porous lactose microparticles using a supercritical carbon dioxide device according to claim 1, characterized in that: In step b, the outlet velocity range of the nozzle (2-1) is 0.1 to 10 m / s, and the spray droplet size range is 1 to 100 μm.

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