Environment-control double-layer composite microbe removal microsphere and preparation method thereof
By designing a double-layer composite microbial removal microsphere with a polylactic acid shell, the problems of poor long-term effectiveness and high environmental risk of existing disinfectants have been solved, achieving efficient and long-lasting disinfection of pathogens and environmental friendliness.
Patent Information
- Application Number
- CN202511688444.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-18
- Publication Date
- 2025-12-16
AI Technical Summary
Existing chemical disinfectants have problems such as poor long-term effectiveness and high risks to the environment and biosafety when eliminating pathogens such as African swine fever virus. Moreover, the disinfection effect is greatly affected by environmental factors.
The product employs an environmentally controlled, dual-layer composite microbial scavenging microsphere. The core consists of nano-sterilization microspheres and stabilizers, while the outer shell is composed of organic solvents and polylactic acid. Through specific ratios and particle size design, a microsphere structure with optimized stability and sustained-release performance is formed.
It achieves long-term and highly effective elimination of pathogens, especially showing sustained inhibitory effects on African swine fever virus, influenza virus, Gram-positive and Gram-negative bacteria, and is environmentally friendly and harmless.
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Figure CN121128734A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of disinfectants, in particular to an environment-controlled double-layer composite microorganism-removing microsphere and a preparation method thereof. BACKGROUND
[0002] African swine fever, zoonotic viruses and aquaculture microorganisms and other pathogens have caused great threat to global livestock and aquaculture industry. African swine fever virus has strong environmental adaptability and transmission ability, can survive in blood for up to 18 months, and even maintain infectivity in frozen pork for many years. In aquaculture, high-density farming environment is easy to cause the spread of pathogens, including bacteria, fungi, viruses and parasites, which pose a serious threat to the health and growth of farmed organisms.
[0003] At present, the chemical disinfectants for these pathogenic environments include aldehyde disinfectants, phenolic disinfectants and halogen disinfectants, etc. Although these chemical disinfectants have broad-spectrum disinfection effect, they have potential risks of carcinogenesis, mutation and respiratory allergy. In aquaculture, chemical disinfectants may affect the balance of bacterial flora in the biological filter, and their residues may endanger the safety of farmed organisms. In addition, the disinfection effect of these chemical disinfectants is greatly affected by environmental factors (such as temperature, pH and organic matter concentration), resulting in their lack of long-term effect and unsatisfactory disinfection effect. SUMMARY
[0004] The present application provides an environment-controlled double-layer composite microorganism-removing microsphere and a preparation method thereof, to solve the problem of lack of long-term effect of existing disinfectants.
[0005] According to a first aspect of the present application, an environment-controlled double-layer composite microorganism-removing microsphere is provided, comprising a core and a shell wrapping the core, the preparation raw materials of the core comprising water, nano disinfection microspheres and a stabilizer, and the preparation raw materials of the shell comprising an organic solvent and polylactic acid. The nano disinfection microspheres are prepared from oil phase raw materials and water phase raw materials; the oil phase raw materials comprise hydrogenated lecithin, distearoyl phosphatidylcholine and cholesterol; and the water phase raw materials comprise polyethyleneimine, polyhexamethylene biguanide and benzalkonium chloride.
[0006] Further, the molar ratio of the hydrogenated lecithin, the distearoyl phosphatidylcholine and the cholesterol is (45-55):(8-12):(35-45).
[0007] Further, the mass ratio of the polyethyleneimine, the polyhexamethylene biguanide and the benzalkonium chloride is (0.5-3):(1-5):(2-8).
[0008] Further, the volume ratio of the oil phase raw material to the water phase raw material is 1: (2-4).
[0009] Further, the weight average molecular weight of the polyethylene imine is 2000-30000.
[0010] Further, the amount of the stabilizer is 1-2% of the mass percentage of the preparation raw material of the inner core.
[0011] Further, the stabilizer is polyvinyl alcohol or cetyltrimethylammonium bromide; the weight average molecular weight of the polyvinyl alcohol is 5000-15000.
[0012] Further, the amount of the polylactic acid is 5%-10% of the mass volume percentage of the preparation raw material of the shell.
[0013] Further, the weight average molecular weight of the polylactic acid is 20000-200000.
[0014] Further, the organic solvent is selected from one or more of dichloromethane, chloroform, benzene, acetone, dimethyl sulfoxide and ethanol.
[0015] Further, the particle size of the environment-controlled disinfection microspheres is 8-15 μm, and the particle size of the nanometer disinfection microspheres is 100-150 nm.
[0016] According to the second aspect of the present application, the present application further provides a preparation method of the above-mentioned environment-controlled double-layer composite microorganism removal microspheres, comprising the following steps: mixing water, nanometer disinfection microspheres and a stabilizer to prepare a continuous phase; mixing an organic solvent and polylactic acid to prepare a dispersed phase; mixing the continuous phase and the dispersed phase to form an emulsion; and stirring, solvent evaporation and freeze-drying the emulsion to obtain the environment-controlled double-layer composite microorganism removal microspheres.
[0017] Further, the preparation method of the environment-controlled double-layer composite microorganism removal microspheres is based on a preparation system of liposome polymer microspheres, and specifically comprises the following steps: injecting the continuous phase and the dispersed phase into the inner flow channel and the outer flow channel of the preparation system of liposome polymer microspheres, respectively; introducing a protective gas into the outer flow channel to push the dispersed phase to pass through the micropores of the preparation system of liposome polymer microspheres, form emulsion droplets in the inner flow channel, and mix with the continuous phase to form an emulsion; after the emulsification is completed, storing the emulsion in the inner flow channel; stirring, solvent evaporation and freeze-drying the emulsion to obtain the environment-controlled double-layer composite microorganism removal microspheres.
[0018] Furthermore, the preparation method of the nano-sterilization microspheres is carried out using a liposome polymer nanosphere preparation system based on Laval nozzle impact jet technology, specifically including the following steps: Hydrogenated lecithin, distearate phosphatidylcholine, and cholesterol were mixed to prepare an oil phase; polyethyleneimine, polyhexamethylene biguanide, and benzalkonium chloride were mixed to prepare an aqueous phase. The oil phase is delivered to one Laval nozzle of the liposome polymer nanosphere preparation system based on Laval nozzle collision jet technology, and the aqueous phase is delivered to another Laval nozzle. The oil phase and the aqueous phase form a high-speed jet through the corresponding Laval nozzles in the liposome polymer nanosphere preparation system based on Laval nozzle collision jet technology. The two high-speed jets collide and mix in the mixing chamber of the liposome polymer nanosphere preparation system based on Laval nozzle collision jet technology to obtain the nano-sterilized microspheres.
[0019] This invention provides an environmental control bilayer composite microbial removal microsphere. Through a unique structural design, the core nano-disinfectant microspheres are prepared from specific types and proportions of oil-phase and aqueous-phase raw materials, effectively killing various pathogens. The outer shell, composed of polylactic acid, provides the microspheres with excellent stability and sustained-release properties, extending the duration of the disinfection effect. Optimized raw material ratios and particle size ranges further enhance the performance of the microspheres, enabling them to maintain high disinfection efficiency in various environments. The environmental control disinfection microspheres of this invention are non-corrosive, possess long-lasting disinfection capabilities, and can effectively kill fungi, algae, and bacteria in various environments. Even after 30 days, they still exhibit high inhibitory effects on bacteria and viruses such as African swine fever ASFV virus, influenza H1S1 virus, Gram-positive Staphylococcus aureus, and Gram-negative Escherichia coli.
[0020] The environmental control dual-layer composite microbial removal microspheres of this invention can provide organisms with an "invisible mask," limiting viral penetration while spraying to kill African swine fever virus and other pathogens in livestock environments. These environmental control dual-layer composite microbial removal microspheres are non-toxic, effectively purifying pathogenic microorganisms in aquatic environments, and are environmentally friendly and harmless.
[0021] The present invention provides a method for preparing environmental control double-layer composite microbial scavenging microspheres, which precisely controls the formation process of the microspheres, ensuring the consistency and stability of product quality, and facilitating large-scale production and application. Attached Figure Description
[0022] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.
[0023] Figure 1 This is a schematic diagram of the structure of the liposome polymer microsphere preparation system provided by the present invention.
[0024] Figure 2 This is a top-view schematic diagram of the membrane emulsification device of the liposome polymer microsphere preparation system provided by the present invention.
[0025] Figure 3 This is a schematic diagram of the filter membrane structure of the membrane emulsification device provided by the present invention.
[0026] Figure 4 yes Figure 3 A magnified structural diagram of point A in the middle.
[0027] Figure 5 This is a flowchart of the preparation method of liposome polymer microspheres provided by the present invention.
[0028] Figure 6 This is an electron micrograph of the liposome polymer microspheres prepared in Example 1.
[0029] Figure 7 This is a schematic diagram of a filter membrane processing system based on a traditional Bessel beam.
[0030] Figure 8 This is a schematic diagram of the filter membrane processing system provided by the present invention.
[0031] Figure 9 This is a schematic diagram illustrating the principle of the reflective axial pyramid provided by the present invention reflecting incident light rays to form a Bessel beam; wherein, The reflectivity of the reflective axial pyramid. The base angle of the reflective axial pyramid. The diffraction angle of the Bessel region; The focal depth of the non-diffraction region of the Bessel beam; Represents the incident laser. The wavelength representing the incident laser light. Represents the radius of the incident laser beam.
[0032] Figure 10 It is the image of the incident laser after passing through the reflective axial pyramid and the spot image at the processing station.
[0033] Figure 11These are simulation diagrams of the transverse and longitudinal light intensity distribution of Bessel and Gaussian beams: (a) and (b) are simulation diagrams of the light field of the Bessel beam; (c) and (d) are simulation diagrams of the light field of the Gaussian beam.
[0034] Figure 12 This invention describes the use of a filter membrane processing system to create 1-micron pores in stainless steel.
[0035] Figure 13 This is a schematic diagram of the structure of the liposome polymer nanosphere preparation system based on Laval nozzle impact jet technology provided by the present invention.
[0036] Figure 14 This is one of the schematic diagrams of the jet mixer in the preparation system of liposome polymer nanospheres based on Laval nozzle collision jet technology provided by the present invention.
[0037] Figure 15 This is the second schematic diagram of the jet mixer structure of the liposome polymer nanosphere preparation system based on Laval nozzle collision jet technology provided by the present invention.
[0038] Figure 16 This is a transmission electron microscope image of the nano-sterilization microspheres obtained in Example 1 of the present invention.
[0039] Figure 17 The diagram shows the bactericidal effect of the environmental control double-layer composite microbial scavenging microspheres obtained in Examples 1 and 2 of this invention on Escherichia coli and Staphylococcus aureus.
[0040] Figure label: 110. Beam shaping assembly; 120. Transmission assembly; 121. Lens; 122. Field lens; 130. Galvanometer assembly; 140. Beam expander; 150. Polarization assembly; 151. Half-wave plate; 152. Polarizer; 160. Laser source; 170. Mirror; 210. Membrane emulsification device; 211. Filter membrane; 212. External flow channel; 213. Internal flow channel; 214. Micropores; 215. Outer shell; 220. Dispersed phase supply device; 221. First dispersed phase storage unit; 222. Second dispersed phase storage unit; 223. First valve body unit; 230. Continuous phase supply device; 231. Continuous phase storage module; 2311. First continuous phase storage unit; 2312. Second continuous phase storage unit; 2313. Second three-way valve; 2314. Fourth three-way valve; 232. Circulation power source; 2321. Circulation pump; 2322. Flow detection unit; 240. Emulsion storage device; 250. Pressure supply device; 251. Air pump; 252. Pressure gauge; 253. Third three-way valve; 254. Sixth three-way valve; 260. Third valve body unit; 310. Jet mixer; 311. Collision mixing unit; 312. Laval nozzle; 320. Oil phase supply device; 330. Aqueous phase supply device. Detailed Implementation
[0041] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.
[0042] In a first typical embodiment of the present invention, the present invention provides an environmental control bilayer composite microbial scavenging microsphere, comprising a core and a shell encapsulating the core, wherein the raw materials for preparing the core include water, nano-sterilization microspheres and a stabilizer, and the raw materials for preparing the shell include an organic solvent and polylactic acid; The nano-sterilization microspheres are prepared from oil-phase raw materials and aqueous-phase raw materials; the oil-phase raw materials include hydrogenated lecithin, distearate phosphatidylcholine and cholesterol; the aqueous-phase raw materials include polyethyleneimine, polyhexamethylene biguanide and benzalkonium chloride.
[0043] This invention encapsulates nano-sterilizing microspheres within a shell composed of organic solvents and polylactic acid, forming an environmentally controlled, bilayered composite microbial scavenging microsphere. This structural design gives the sterilizing microspheres better stability and sustained-release properties. The nano-sterilizing microspheres in the core provide highly efficient sterilization, while the shell protects the active ingredients within the core, preventing premature release or inactivation during storage and transportation. Simultaneously, it controls the release rate of the sterilizing components, extending the duration of the sterilization effect and maintaining good sterilization performance under various environments.
[0044] According to some specific embodiments of the present invention, the molar ratio of the hydrogenated lecithin, the distearate phosphatidylcholine, and the cholesterol is (45~55):(8~12):(35~45). This optimized ratio helps to form a stable oil-phase structure. This stable oil-phase structure can better mix with aqueous raw materials, thereby improving the quality and performance of the nano-sterilization microspheres, enabling them to release the active ingredients more uniformly during sterilization, and enhancing the stability and reliability of the sterilization effect.
[0045] The preferred molar ratio of the hydrogenated lecithin, the distearate phosphatidylcholine, and the cholesterol is (48~52):(9~11):(38~42). In some specific embodiments, the molar ratio of the hydrogenated lecithin, the distearate phosphatidylcholine, and the cholesterol is 50:10:40.
[0046] According to some specific embodiments of the present invention, the mass ratio of the polyethyleneimine, the polyhexamethylene biguanide, and the benzalkonium chloride is (0.5~3):(1~5):(2~8). This specific mass ratio enables the three components to have a synergistic effect, fully utilize their respective disinfection properties, improve the killing ability of disinfection microspheres against different pathogens, enhance the broad-spectrum and high-efficiency of disinfection effect, and at the same time help to optimize the physicochemical properties of the nano-disinfection microspheres, such as particle size and dispersibility, thereby improving their performance in practical applications.
[0047] The preferred mass ratio of the polyethyleneimine, the polyhexamethylene biguanide, and the benzalkonium chloride is (1~2.5):(2.5~4):(4~5).
[0048] In some specific embodiments, the mass ratio of the polyethyleneimine, the polyhexamethylene biguanide, and the benzalkonium chloride is 2.5:2.5:5. In other specific embodiments, the mass ratio of the polyethyleneimine, the polyhexamethylene biguanide, and the benzalkonium chloride is 1:4:4.
[0049] According to some specific embodiments of the present invention, the volume ratio of the oil phase raw material to the aqueous phase raw material is 1:(2~4), which is crucial for the preparation process of nano-sterilization microspheres. A suitable volume ratio ensures sufficient contact and reaction between the oil and aqueous phases during mixing, forming uniform and stable nano-sterilization microspheres. An improper ratio may lead to problems such as uneven particle size, poor dispersibility, or uneven component distribution of the microspheres, thereby affecting the sterilization effect.
[0050] The preferred volume ratio of the oil phase raw material to the aqueous phase raw material is 1:(2.5~3.5). In some specific embodiments, the volume ratio of the oil phase raw material to the aqueous phase raw material is 1:3.
[0051] The molecular weight of polyethyleneimine has a significant impact on its performance in nano-sterilization microspheres. To further improve the sterilization performance of the nano-sterilization microspheres, the weight-average molecular weight of the polyethyleneimine is further set to 2000-30000.
[0052] The weight-average molecular weight of the polyethyleneimine is preferably 3000-6000. Within this molecular weight range, polyethyleneimine can better interact with other components to form stable nanostructures while maintaining good solubility and dispersibility. Lower molecular weight polyethyleneimine may have better solubility but may be slightly less stable; while higher molecular weight polyethyleneimine has better stability, but its solubility may be affected. Therefore, limiting the molecular weight range achieves a balance between stability and solubility, allowing polyethyleneimine to exert its optimal performance in nano-sterilization microspheres, improving the sterilization effect and durability of the microspheres.
[0053] According to some specific embodiments of the present invention, the amount of stabilizer is 1-2% of the mass percentage of the raw materials used to prepare the core. This ratio can effectively stabilize the nano-sterilization microspheres in the core, preventing them from agglomerating or precipitating during preparation and storage, thereby ensuring the uniformity and stability of the sterilization microspheres.
[0054] According to some specific embodiments of the present invention, the stabilizer is polyvinyl alcohol or hexadecyltrimethylammonium bromide; polyvinyl alcohol or hexadecyltrimethylammonium bromide, as a stabilizer, has good stability and compatibility.
[0055] The polyvinyl alcohol has a weight-average molecular weight of 5,000-15,000, which allows it to stabilize the nano-sterilization microspheres without affecting other properties of the microspheres, such as particle size and dispersibility. This further ensures the quality and performance of the environmental control sterilization microspheres, giving them better stability and reliability in practical applications.
[0056] The weight-average molecular weight of the polyvinyl alcohol is preferably 8000-12000. In some specific embodiments, the weight-average molecular weight of the polyvinyl alcohol is 10000.
[0057] According to some specific embodiments of the present invention, the amount of polylactic acid used accounts for 5%-10% of the mass-volume percentage of the raw materials used to prepare the shell. This range enables the polylactic acid to have appropriate thickness and strength when forming the shell, effectively encapsulating the core while ensuring the overall performance of the microspheres.
[0058] Optionally, the amount of polylactic acid used as a percentage of the mass volume of the raw materials used to prepare the shell can be 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, or 10%, etc., or other values within the above range, which are not limited here.
[0059] According to some specific embodiments of the present invention, the polylactic acid has a weight-average molecular weight of 20,000-200,000. Polylactic acid in this weight-average molecular weight range has good biocompatibility and biodegradability, while also providing sufficient mechanical strength to protect the core.
[0060] According to some specific embodiments of the present invention, the organic solvent is selected from one or more of dichloromethane, chloroform, benzene, acetone, dimethyl sulfoxide, and ethanol, preferably dichloromethane. The wide range of organic solvents provides various options for the dissolution and dispersion of polylactic acid. Appropriate solvents can be selected based on the actual preparation process and requirements to ensure uniform shell formation and quality control, thereby improving the overall performance and application effect of the environmental control bilayer composite microbial scavenging microspheres.
[0061] According to some specific embodiments of the present invention, the particle size of the environmental control bilayer composite microbial removal microspheres is 8-15 μm, and the particle size of the nano-disinfectant microspheres is 100-150 nm. The limitation of the above particle size range is of great significance to the performance and application effect of the microspheres. Smaller nano-disinfectant microsphere particle size allows for a larger specific surface area, thereby improving the release efficiency of disinfectant components and the opportunity for contact with pathogens, thus enhancing the disinfection effect. The particle size of the environmental control bilayer composite microbial removal microspheres ensures effective encapsulation of the nano-disinfectant microspheres while maintaining good dispersibility and suspension, facilitating uniform distribution and use in practical applications. Furthermore, a suitable particle size range also helps control the sedimentation rate and stability of the microspheres, enabling them to maintain good performance during storage and use, and extending their service life.
[0062] In a second typical embodiment of the present invention, the present invention also provides a system for preparing liposome polymer microspheres, such as... Figures 1 to 4 As shown, a specific embodiment of the first aspect of the present invention provides a system for preparing liposome polymer microspheres. The system includes a membrane emulsification device 210; the membrane emulsification device 210 includes a plurality of filter membranes 211; the plurality of filter membranes 211 are arranged in parallel; an external flow channel 212 is formed between two adjacent filter membranes 211; an internal flow channel 213 is formed within the filter membrane 211 along its own axial direction; a plurality of micropores 214 are formed on the wall of the filter membrane 211; the external flow channel 212 communicates with the internal flow channel 213 through the micropores 214.
[0063] In this embodiment, by arranging multiple filter membranes 211 in parallel, a large amount of raw materials can be processed simultaneously, significantly increasing the microsphere yield per unit time. This overcomes the bottleneck of low efficiency in traditional single filter membranes, making it suitable for industrial-scale production. It also solves the problem of limited output of existing membrane emulsification devices 210, which require multiple devices 210 to participate simultaneously in the emulsification process in large-scale emulsification scenarios, leading to high costs. Furthermore, the filter membrane in this embodiment is free of dead pores, solving the problem of dead pores in existing ceramic-sintered SPG membranes, which makes thorough cleaning and backwashing difficult.
[0064] Furthermore, the outer flow channels 212 between adjacent filter membranes 211 form directional fluid channels, which, together with the micropores 214, enable a more uniform transmembrane pressure distribution, avoiding localized eddies or dead zones. The inner flow channels 213 and outer flow channels 212, through the micropores 214, form controllable cross-flow shear forces, which is beneficial for generating microspheres with better dispersion. The parallel modular design allows for flexible increases or decreases in the number of filter membranes 211, satisfying both small-scale process optimization and scaling up to large-scale production. Filter membranes 211 can be maintained or replaced individually, reducing overall downtime losses due to localized blockage or damage. The collaborative work of multiple filter membranes 211 maintains more stable transmembrane pressure, and combined with the uniformity of the micropore size 214, ensures uniform microsphere particle size.
[0065] Optionally, adjacent filter membranes 211 are arranged at intervals. The interval arrangement of filter membranes 211 can reduce vibration interference and avoid the risk of mechanical damage to filter membranes 211 caused by dense arrangement.
[0066] Furthermore, the micropores 214 on the filter membrane 211 can be formed by laser processing. The micropores 214 formed by laser processing have a uniform pore distribution, which improves the uniformity of emulsification and solves the problem of random pore distribution and limited emulsification uniformity in existing SPG membranes formed by ceramic sintering.
[0067] Preferably, the micropores 214 on the filter membrane 211 are formed using a reflective Bezier beam processing method. In the prior art, micropores are typically formed by ceramic sintering, resulting in randomly distributed channels. This limits the emulsification uniformity of the membrane emulsification device. Furthermore, because random channels are prone to dead pores, thorough cleaning and backflushing are difficult, posing challenges for use in GMP (cleanroom) facilities. In this embodiment, the micropores 214 on the filter membrane 211 are preferably formed using a reflective Bezier beam processing method, which avoids dead pores and provides better pore size uniformity for the micropores 214.
[0068] It should be noted that reflective Bessel beams can be generated by a filter membrane processing system.
[0069] Optionally, the micropores 214 on the filter membrane 211 can be made of... Figure 8The filter membrane processing system shown is used for processing. The structure and working principle of the filter membrane processing system of the present invention will be described in detail below.
[0070] In the late 1980s, Durnin of the University of Rochester formally proposed the concept of a diffraction-free beam. He essentially discovered a set of rigorous solutions to the zeroth-order Bessel function form of Maxwell's wave equation and experimentally proved, using simple optical components, that the corresponding wave of this particular solution is a Bessel beam, exhibiting diffraction-free characteristics. Due to the excellent optical propagation properties of diffraction-free Bessel beams, their research quickly attracted widespread attention from research groups both domestically and internationally.
[0071] The wave equation for an ideal Bessel beam is given by formula (1): Formula (1).
[0072] In formula (1), t represents electric field intensity; r represents spatial position coordinates; t represents time; c is the speed of light in vacuum. For the second-order partial derivative with respect to time; It is the Laplace operator.
[0073] A particular solution along the Z-axis can be expressed as formula (2):
[0074] In formula (2), ε represents the electric field strength; r represents the spatial coordinates; t represents time; exp is the natural exponential function; i is the imaginary unit; For the longitudinal component of the propagation constant; ω is the angular frequency; z is the spatial coordinate along the main propagation direction of the beam (i.e., the Z-axis); For the transverse component of the propagation constant; The azimuth angle is x; x and y are rectangular coordinates in a plane perpendicular to the beam propagation direction (i.e., the Z-axis). Radial coordinates; This is a Bessel function.
[0075] For an ideal Bessel beam, its cross-sectional intensity distribution A Bessel beam is characterized by a central spot (main lobe) and numerous concentric rings (side lobes). The energy density of the main lobe is much higher than that of the side lobes, and the light intensity decreases sequentially from the inside out. However, the energy carried by the main lobe is equal to that of the side lobes, and the intensity distribution does not change with increasing propagation distance. The intensity of a Bessel beam does not change with propagation distance; this is commonly referred to as its "diffraction-free characteristic." Since the laser beam emitted from a laser in a real optical system is limited by an aperture, its beam width and energy are finite. In experiments, only an approximate Bessel beam can be obtained; that is, its "diffraction-free characteristic" manifests in practice as a limited distance along the propagation direction. Within this range, the lateral light intensity distribution remains essentially constant. Once this maximum distance is exceeded, the beam diverges and loses its "non-diffraction characteristic".
[0076] like Figure 11 These are simulation diagrams of the transverse and longitudinal light intensity distribution of Bessel and Gaussian beams: (a) and (b) are simulation diagrams of the light field of the Bessel beam; (c) and (d) are simulation diagrams of the light field of the Gaussian beam.
[0077] Figure 7 This is a schematic diagram of a filter film processing system based on a traditional Bessel beam. The laser source emits a laser beam, which, after passing through a beam expander, is incident on a transmission axial pyramid. The transmission axial pyramid transmits the incident Gaussian beam and converts it into a Bessel beam. This Bessel beam is then focused onto the processing station by a lens to drill holes in the workpiece. However, this transmission axial pyramid is not suitable for high-power laser drilling requirements.
[0078] like Figure 8 As shown in the figure, a specific embodiment of the present invention provides a filter membrane processing system. The filter membrane processing system includes a beam shaping component 110 and a transmission component 120; the beam shaping component 110 is used to reflect the incident laser and convert it into a Bessel beam; the transmission component 120 is disposed in the optical path of the Bessel beam and is used to transmit the non-diffraction region of the Bessel beam to the processing station.
[0079] In this embodiment, the incident laser beam is reflected and converted into a Bessel beam by the beam shaping component 110, instead of being transmitted to form a Bessel beam. Then, the non-diffraction region of the Bessel beam is transmitted to the processing station by the transmission component 120, allowing drilling of the workpiece placed at the processing station. The reflective design avoids energy absorption by the transmission element, making it suitable for long-term high-power processing. The reflective design does not require consideration of the material's transmittance, supporting incident lasers from the ultraviolet to the infrared band. The reflective design eliminates the thermal lensing effect, resulting in high focal depth stability in the non-diffraction region of the Bessel beam, and also avoids the aperture inconsistency problem caused by heat accumulation in the transmission method.
[0080] Furthermore, the incident laser is a pulsed laser.
[0081] Furthermore, the beam shaping assembly 110 includes a reflective axial pyramid; the reflective axial pyramid is positioned in the optical path of the incident laser to reflect the incident laser and convert it into a Bessel beam. The reflective design avoids the dispersion problems of the transmitting material and is suitable for multi-wavelength / ultrafast lasers. The metal reflective film of the reflective axial pyramid (such as a gold film with an infrared reflectivity >98%) can withstand kilowatt-level lasers without thermal lensing effects. The reflection angle allows for a foldable optical path, saving space and making it suitable for integrated equipment.
[0082] As Figure 10 The images shown, including the incident laser after passing through the reflective axial pyramid and the spot image at the machining station, demonstrate that the reflective axial pyramid can convert the incident laser into a Bessel beam, and the transmission component can transmit the Bessel beam to the machining station.
[0083] like Figure 9 As shown, the base angle α of the reflective axial pyramid is further ranging from 0.5° to 15°. This design allows for flexible adaptation to different precision machining requirements while avoiding the limitations of traditional transmission-type axial pyramids. For example, Preferably, the base angle α of the reflective axial pyramid is 2° to 5°, which is suitable for long focal depths and wide-range processing.
[0084] like Figure 9 As shown, furthermore, the angle γ between the incident laser and the normal of the reflecting axial pyramid is half the base angle α. This further ensures the quality of the Bessel beam formed after passing through the reflecting axial pyramid.
[0085] Furthermore, the focal depth of the non-diffraction region is greater than the thickness of the filter membrane tube wall, ensuring that the non-diffraction region can cover the filter membrane tube wall, and micropores that penetrate the filter membrane tube wall can be punched on the filter membrane.
[0086] like Figure 9 As shown, after passing through the reflective axial pyramid, the focal depth of the Bessel beam is... The focal spot diameter of the Bessel beam is... ,in Let be the focal radius of the Bessel beam.
[0087] in, The diffraction angle in the Bessel region can also be described as follows: The angle between the Bessel region and the optical axis of the reflected beam is π; π is 3.1415926. Represents the radius of the incident laser beam; The focal depth is the non-diffraction region of the Bessel beam.
[0088] For example, if the actual diameter of the emitted Bessel spot is 100 micrometers, but the required spot diameter for processing is 20 micrometers, then the focal length ratio of the field lens to the lens is 1:5.
[0089] In some embodiments, the filter membrane processing system further includes a galvanometer assembly 130; the galvanometer assembly 130 is disposed in the optical path of the Bessel beam and is used to adjust the deflection direction of the Bessel beam. By setting the galvanometer assembly 130, the deflection of the Bessel beam can be controlled, enabling rapid movement of the light spot on the workpiece. The operating speed of the galvanometer can generally reach 10 m / s, for example, the ExtraScan10 galvanometer.
[0090] Furthermore, the transfer assembly 120 includes a lens 121 and a field lens 122; the lens 121 is disposed at the incident end of the galvanometer assembly 130 and is used to focus the Bessel beam onto the galvanometer assembly 130; the field lens 122 is disposed at the exit end of the galvanometer assembly 130 and forms a 4F system with the lens 121, so that the field lens 122 transfers the non-diffraction region of the Bessel beam to the processing station.
[0091] In this embodiment, lens 121 and field lens 122 follow a 4F system to ensure that the diffraction-free characteristics of the Bessel beam are not compromised during scanning; wavefront distortion caused by traditional field lenses is avoided; and the depth of focus retention in the diffraction-free region is higher in this embodiment compared to non-4F systems. The galvanometer is placed on the central image plane of the 4F system, and its deflection only changes the beam angle rather than the focusing position, achieving zero field distortion and dynamic processing consistency.
[0092] Optionally, lens 121 is positioned at a distance from the optical center of the Bessel beam reflected and converged by beam shaping assembly 110, equal to the focal length of lens 121. In other words, the optical center of lens 121 must coincide with the optical axis of the Bessel beam, and the distance between lens 121 and the reflective axial pyramid must be equal to the focal length of lens 121. This allows the non-diffraction region of the Bessel beam to be effectively transferred to the processing station.
[0093] Furthermore, the filter membrane processing system also includes a beam expander 140; the beam expander 140 is disposed in the optical path of the incident laser and is used to adjust the beam size and / or divergence angle of the incident laser. Specifically, the beam expander 140 is disposed at the incident end of the reflective axial pyramid, and the incident laser passes through the beam expander 140 and is incident on the reflective axial pyramid; the reflective axial pyramid is used to reflect the incident laser and convert it into a Bessel beam.
[0094] Optionally, the beam expander 140 can be a 1x to 8x beam expander 140.
[0095] Furthermore, the filter membrane processing system also includes a laser source 160; the laser source 160 is used to emit incident laser light; the wavelength of the incident laser light... satisfy: In other words, the incident laser wavelength of the filter membrane processing system in this embodiment covers a broad band from deep ultraviolet (DUV) to terahertz (THz).
[0096] Optionally, the laser source 160 includes, but is not limited to, a picosecond laser.
[0097] Furthermore, the filter membrane processing system also includes a reflector 170; the reflector 170 is disposed at the exit end of the beam expander 140 and is used to reflect the beam emitted from the beam expander 140 to the reflective axial pyramid. By setting the reflector 170, the direction of the incident laser can be changed, making the layout of the entire system more flexible.
[0098] Furthermore, the filter membrane processing system also includes a polarization component 150; the polarization component 150 is positioned between the beam expander 140 and the laser source 160; the incident laser passes through the polarization component 150 and is directed towards the beam expander 140. This design can further optimize the polarization state of the incident laser to improve system efficiency and energy distribution; it also allows control of the shape of the filter membrane perforations by preset polarization direction. The polarization component 150 can block back-reflected light (such as laser light reflected from the processing station) from returning to the laser source 160, preventing instability or damage to the light source.
[0099] Optionally, the polarization assembly 150 includes a polarizer 152 and a half-wave plate 151; the half-wave plate 151 is disposed between the laser source 160 and the polarizer 152.
[0100] It should be noted that the material of the filter membrane is not limited in the specific embodiments of the present invention. Optionally, the filter membrane can be made of metal. Metals include, but are not limited to, stainless steel, copper, and aluminum. Figure 12 The filter membrane processing system of this embodiment is used to drill 1-micron pores in stainless steel.
[0101] A specific embodiment of the present invention provides a filter membrane processing method. This filter membrane processing method employs the filter membrane processing system described in any of the above embodiments. The filter membrane processing method includes: S100. Place the workpiece to be processed in the processing station of the filter membrane processing system.
[0102] S200, the incident laser is emitted into the beam shaping assembly 110, and the beam shaping assembly 110 reflects the incident laser and converts it into a Bessel beam.
[0103] Specifically, the laser source 160 is activated to emit an incident laser. The incident laser passes through a half-wave plate 151, a polarizer 152, a beam expander 140, and a reflector 170 before being incident on a reflective axial pyramid. The reflective axial pyramid reflects the incident laser and converts it into a Bessel beam.
[0104] S300 and the transfer component 120 transfer the non-diffraction region of the Bessel beam to the processing station to process micropores on the workpiece to obtain a filter membrane.
[0105] Specifically, the Bessel beam is focused by lens 121 onto galvanometer assembly 130; the Bessel beam emitted from galvanometer assembly 130 is focused by field lens 122 to transmit the non-diffraction region of the Bessel beam to the processing station, thereby realizing the drilling of the workpiece to be processed; the deflection of the Bessel beam is adjusted by galvanometer assembly 130 to achieve dynamic drilling, and finally the filter membrane is obtained.
[0106] Furthermore, the pore size of the micropore 214 is from 0.1 micrometers to 40 micrometers. In other words, the pore size of the micropore 214 can be 0.1 micrometers, 40 micrometers, or any value between 0.1 micrometers and 40 micrometers. The specific value of the pore size of the micropore 214 is not limited in the specific embodiments of the invention.
[0107] like Figure 2 As shown, the membrane emulsification device 210 further includes a housing 215; the housing 215 has a receiving cavity inside; multiple filter membranes 211 are arranged in parallel in the receiving cavity; and an outer flow channel 212 is located in the receiving cavity. The housing 215 has a dispersed phase inlet, a continuous phase inlet, and a continuous phase outlet; the dispersed phase inlet is connected to the outer flow channel 212, the continuous phase inlet is connected to one end of the inner flow channel 213, and the continuous phase outlet is connected to the other end of the inner flow channel 213.
[0108] In this embodiment, the receiving cavity provides installation space for the filter membrane 211, and the outer shell 215 isolates the filter membrane 211 from the outside world to prevent environmental particles or microorganisms from contaminating the microsphere product. This is especially suitable for pharmaceutical-grade liposomes with sterility requirements (such as vaccine carriers and nucleic acid delivery systems).
[0109] Optionally, multiple filter membranes 211 are arranged in a periodic array within the receiving cavity.
[0110] Optionally, the outer casing 215 is also provided with a vent for venting air; the vent is connected to the outer flow channel 212. When the dispersed phase is injected into the outer flow channel 212, the vent can be opened to vent the air in the outer flow channel 212 and the inner flow channel 213.
[0111] In some embodiments, the liposome polymer microsphere preparation system further includes an emulsion storage device 240; the emulsion storage device 240 is connected to an inner flow channel 213 and is used to store the emulsion discharged from the inner flow channel 213. Specifically, a continuous phase outlet is connected to the emulsion storage device 240 and is used to discharge the emulsion from the inner flow channel 213 into the emulsion storage device 240 for storage.
[0112] In this embodiment, the continuous phase outlet is directly connected to the emulsion storage device 240 (such as a buffer tank with stirring) to achieve immediate collection and stable storage of the emulsion and avoid droplet aggregation.
[0113] Furthermore, the emulsion storage device 240 includes a third storage tank and a third agitator; the third storage tank is connected to the inner flow channel 213 and is used to store the emulsion. The third agitator is installed in the third storage tank to reduce the risk of emulsion droplet aggregation in the emulsion.
[0114] In some embodiments, the liposome polymer microsphere preparation system further includes a pressure supply device 250; the pressure supply device 250 is connected to the outer channel 212 and is used to introduce a protective gas into the outer channel 212 to push the dispersed phase through the micropores 214 to form droplets in the inner channel 213.
[0115] In this embodiment, by setting up a pressure supply device 250, the speed at which the dispersed phase (such as the oil phase) permeates through the micropores 214 can be controlled by adjusting the gas pressure (such as nitrogen or air), thereby achieving dynamic control of droplet formation. Compared to mechanical pumping, gas pressure drive is more stable and avoids uneven droplet size caused by pulsed flow. The gas forms an "air cushion" barrier in the outer flow channel 212, reducing direct contact between the two phases and preventing component mixing (such as surfactant migration). Gas-assisted propulsion can reduce the retention of high-viscosity dispersed phase in the micropores 214, reducing the probability of clogging.
[0116] Furthermore, the pressure supply device 250 includes a gas tank (not shown in the figure), an air pump 251, and a pressure regulator 252. The gas tank stores protective gas. The inlet of the air pump 251 is connected to the outlet of the gas tank, and the outlet of the air pump 251 is connected to the outer flow channel 212 for supplying protective gas to the outer flow channel 212. The pressure regulator 252 is located at the outlet of the air pump 251 and is used to adjust the gas pressure entering the outer flow channel 212. The gas pressure entering the outer flow channel 212 can be adjusted by adjusting the pressure regulator 252 according to the viscosity of the dispersed phase and the target particle size of the microspheres to prepare microspheres that meet the target particle size.
[0117] Optional, the protective gas includes, but is not limited to, nitrogen.
[0118] Furthermore, the pressure supply device 250 also includes a sixth three-way valve 254 and a third three-way valve 253; the inlet of the sixth three-way valve 254 is connected to the outlet of the air pump 251, and the first outlet of the sixth three-way valve 254 is connected to the outer flow channel 212; the second outlet of the sixth three-way valve 254 is connected to the inlet of the third three-way valve 253, the first outlet of the third three-way valve 253 is connected to the inlet of the first dispersed phase storage unit 221, and the second outlet of the third three-way valve 253 is connected to the inlet of the second dispersed phase storage unit 222. When it is necessary to inject the dispersed phase of the first dispersed phase storage unit 221 into the outer flow channel 212, the gas discharged by the air pump 251 can enter the inlet of the third three-way valve 253 through the second outlet of the sixth three-way valve 254, and enter the first dispersed phase storage unit 221 from the first outlet of the third three-way valve 253, so as to force the dispersed phase into the outer flow channel 212. When it is necessary to inject the dispersed phase from the second dispersed phase storage unit 222 into the outer flow channel 212, the gas discharged by the air pump 251 can enter the inlet of the third three-way valve 253 through the second outlet of the sixth three-way valve 254, and then enter the second dispersed phase storage unit 222 from the second outlet of the third three-way valve 253, so as to force the dispersed phase into the outer flow channel 212. When it is necessary to pressurize the outer flow channel 212, the protective gas discharged by the air pump 251 is discharged into the outer flow channel 212 through the first outlet of the sixth three-way valve 254.
[0119] In some embodiments, the liposome polymer microsphere preparation system further includes a dispersed phase supply device 220 and a continuous phase supply device 230; the dispersed phase supply device 220 is connected to the outer channel 212 for injecting the dispersed phase into the outer channel 212; the continuous phase supply device 230 is connected to the inner channel 213 to form a continuous phase circulation loop.
[0120] In this embodiment, the flow pattern of the dispersed phase in the outer channel 212 and the continuous phase in the inner channel 213 enhances the turbulence effect, reduces the risk of micropore 214 clogging, and increases flux. Furthermore, the two phases mix rapidly near the inner surface of the filter membrane 211, avoiding pre-emulsification and reducing batch variations caused by phase separation.
[0121] Furthermore, the dispersed phase supply device 220 includes a dispersed phase storage module; the dispersed phase storage module includes a first dispersed phase storage unit 221, a second dispersed phase storage unit 222, and a first valve body unit 223; both the first dispersed phase storage unit 221 and the second dispersed phase storage unit 222 are used to store dispersed phase; the first valve body unit 223 has a first conducting state and a second conducting state; in the first conducting state, the first dispersed phase storage unit 221 injects dispersed phase into the outer flow channel 212; in the second conducting state, the second dispersed phase storage unit 222 injects dispersed phase into the outer flow channel 212. This design ensures continuous production of the system. For example, after the dispersed phase stored in the first dispersed phase storage unit 221 is used up, the first valve body unit 223 can be switched from the first conducting state to the second conducting state, so that the dispersed phase in the second dispersed phase storage unit 222 is injected into the outer flow channel 212, thereby ensuring the continuity of production.
[0122] Furthermore, the first dispersed phase storage unit 221 includes a first storage tank and a first stirrer; the first stirrer is installed inside the first storage tank, which contains the dispersed phase. By providing the first stirrer, the dispersiond phase can be prevented from accumulating inside the first storage tank.
[0123] Optionally, the first dispersed phase storage unit 221 and the second dispersed phase storage unit 222 may have the same structure.
[0124] It should be noted that, in this embodiment, there is no limitation on the number of the first dispersed phase storage unit 221 and the second dispersed phase storage unit 222.
[0125] Furthermore, the first valve body unit 223 includes a first three-way valve; the outer flow channel 212 is connected to the first dispersed phase storage unit 221 and the second dispersed phase storage unit 222 respectively through the first three-way valve. Specifically, the first inlet of the first three-way valve is connected to the outlet of the first dispersed phase storage unit 221, the second inlet of the first three-way valve is connected to the outlet of the second dispersed phase storage unit 222, and the outlet of the first three-way valve is connected to the outer flow channel 212 through the dispersion inlet.
[0126] Preferably, the first three-way valve is an electromagnetic three-way valve, which facilitates automated control.
[0127] Furthermore, the continuous phase supply device 230 includes a continuous phase storage module 231 and a circulation power source 232. The continuous phase storage module 231 is used to store the continuous phase. The inlet of the continuous phase storage module 231 is connected to the outlet of the inner flow channel 213, and the outlet of the continuous phase supply device 230 is connected to the inlet of the inner flow channel 213 to form a continuous phase circulation loop. The circulation power source 232 is disposed in the continuous phase circulation loop. When it is necessary to inject the continuous phase into the inner flow channel 213, the circulation power source 232 is activated, and the continuous phase in the continuous phase storage module 231 enters the inner flow channel 213. The continuous phase injected into the inner flow channel 213 washes the inner surface of the filter membrane 211, causing the emulsion droplets to peel off from the micropores 214 and disperse into the continuous phase, and finally return to the continuous phase storage module 231. After the emulsification process is completed, the emulsion in the inner flow channel 213 can be discharged into the emulsion storage device 240 for storage.
[0128] Furthermore, the continuous phase storage module 231 includes a first continuous phase storage unit 2311, a second continuous phase storage unit 2312, and a second valve body unit. Both the first and second continuous phase storage units 2311 and 2312 are used to store the continuous phase. The second valve body unit has a third open state and a fourth open state. In the third open state, the first continuous phase storage unit 2311 injects the continuous phase into the inner flow channel 213; in the fourth open state, the second continuous phase storage unit 2312 injects the continuous phase into the inner flow channel 213. This design ensures continuous production of the system. For example, after the continuous phase stored in the first continuous phase storage unit 2311 is used up, the second valve body unit can be switched from the third open state to the fourth open state, allowing the continuous phase in the second continuous phase storage unit 2312 to be injected into the inner flow channel 213, thus ensuring the continuity of production.
[0129] Optionally, the second continuous phase storage unit 2312 includes a second storage tank and a second stirrer; the second stirrer is installed inside the second storage tank, which contains the continuous phase. The second stirrer helps prevent the accumulation of emulsion droplets within the second storage tank.
[0130] Optionally, the first continuous phase storage unit 2311 and the second continuous phase storage unit 2312 may have the same structure.
[0131] Optionally, the second valve body unit includes a second three-way valve 2313 and a fourth three-way valve 2314; the inlet of the inner flow channel 213 is connected to the outlet of the first continuous phase storage unit 2311 and the outlet of the second continuous phase storage unit 2312 through the second three-way valve 2313; the outlet of the inner flow channel 213 is connected to the inlet of the first continuous phase storage unit 2311 and the inlet of the second continuous phase storage unit 2312 through the fourth three-way valve 2314. Specifically, the first inlet and outlet of the second three-way valve 2313 are connected to the outlet of the first continuous phase storage unit 2311, the second inlet of the second three-way valve 2313 is connected to the outlet of the second continuous phase storage unit 2312, and the outlet of the second three-way valve 2313 is connected to the inlet of the inner flow channel 213 through the circulating power source 232. The first outlet of the fourth three-way valve 2314 is connected to the inlet of the first continuous phase storage unit 2311, the second outlet of the second three-way valve 2313 is connected to the inlet of the second continuous phase storage unit 2312, and the inlet of the second three-way valve 2313 is connected to the outlet of the inner flow channel 213.
[0132] Preferably, the second three-way valve 2313 is an electromagnetic three-way valve, which facilitates automated control.
[0133] Preferably, the fourth three-way valve 2314 is an electromagnetic three-way valve, which facilitates automated control.
[0134] Furthermore, the circulating power source 232 includes a circulating pump 2321 and a flow detection unit 2322; the flow detection unit 2322 is located at the outlet of the circulating pump 2321 and is used to detect the flow rate of the continuous phase.
[0135] Optionally, the flow detection unit 2322 includes a flow meter.
[0136] In some embodiments, the liposome polymer microsphere preparation system further includes a third valve unit 260; an emulsion storage device 240 is connected to the outlet of an inner flow channel 213; the third valve unit 260 has a fifth open state and a sixth open state; in the fifth open state, a continuous phase supply device 230 is connected to the inner flow channel 213 to form a continuous phase circulation loop; in the sixth open state, the inlet of the inner flow channel 213 is connected to the emulsion storage device 240 for discharging the emulsion.
[0137] Specifically, the third valve body unit 260 includes a fifth three-way valve; the inlet of the fifth three-way valve is connected to the outlet of the inner flow channel 213, the first outlet of the fifth three-way valve is connected to the emulsion storage device 240, and the second outlet of the fifth three-way valve is connected to the inlet of the fourth three-way valve 2314.
[0138] Optionally, the fifth three-way valve can be a solenoid three-way valve for easy automated control.
[0139] It should be noted that liposome polymer microspheres are an advanced drug delivery carrier that combines the advantages of both liposomes and polymer microspheres, possessing a unique "core-shell" or "hybrid network" structure. Liposome polymer microspheres consist of a liposome portion and a polymer portion.
[0140] like Figure 5 As shown, in a third typical embodiment of the present invention, the present invention also provides a method for preparing liposome polymer microspheres. This preparation method uses the liposome polymer microsphere preparation system described in any of the above embodiments. The preparation method includes: S10. Inject the dispersed phase into the outer channel 212 and inject the continuous phase into the inner channel 213.
[0141] Specifically, the dispersed phase in the dispersed phase storage module is circulated and injected into the outer flow channel 212 to fill the outer flow channel 212; the circulation power source 232 is started to circulate and inject the continuous phase in the continuous phase storage module 231 into the inner flow channel 213.
[0142] S20. A protective gas is introduced into the outer flow channel 212 to push the dispersed phase through the micropores 214, forming droplets in the inner flow channel 213, and mixing with the continuous phase to form an emulsion.
[0143] Specifically, when the pressure supply device 250 is turned on, protective gas enters the outer flow channel 212. The dispersed phase will pass through the micropores 214 under the push of the high-pressure gas, form droplets in the inner flow channel 213, and disperse into the continuous phase under the scouring of the continuous phase to form an emulsion.
[0144] S30. After emulsification is completed, the emulsion in the inner channel 213 is discharged into the emulsion storage device 240 for storage.
[0145] Specifically, after emulsification is completed, the circulating power source 232 is stopped, the conduction state of the third valve body unit 260 is switched, and the emulsion in the inner flow channel 213 is discharged into the emulsion storage device 240 for storage.
[0146] S40. The emulsion is stirred, the solvent is evaporated, and the emulsion is freeze-dried to obtain liposome polymer microspheres.
[0147] Specifically, the emulsion storage device 240 stirs the emulsion at low speed, evaporates the solvent, and finally freeze-dries it to obtain microspheres.
[0148] In this embodiment, the liposome polymer microsphere preparation system of any of the above embodiments is used, thus possessing at least the aforementioned advantages. Furthermore, the liposome polymer microsphere preparation system of any of the above embodiments can also successfully prepare liposome polymer microspheres with uniform particle size.
[0149] In a fourth typical embodiment of the present invention, the present invention also provides a system for preparing liposome polymer nanospheres based on Laval nozzle impact jet technology. For example... Figures 13-15 As shown, the preparation system includes a jet mixer 310; the jet mixer 310 includes a collision mixing unit 311 and at least two Laval nozzles 312; the collision mixing unit 311 has a mixing chamber, and at least one liquid outlet channel and at least two liquid inlet channels are formed in the collision mixing unit 311; the liquid inlet channels and the liquid outlet channels are both connected to the mixing chamber; a plurality of Laval nozzles 312 are arranged one-to-one in the liquid inlet channels.
[0150] In this embodiment, by setting a Laval nozzle 312 in the inlet channel, the Laval nozzle 312 can accelerate the passing fluid to a supersonic state through its own contraction-expansion structure, forming a high-energy jet. Two high-speed jets are ejected from different jet outlets and meet and collide violently in the mixing chamber. This not only increases the contact area of the fluid but also significantly enhances the mixing uniformity by shear force and turbulence, rapidly disrupting the stable interface in laminar flow and achieving nanoscale dispersion of the fluid. Furthermore, the instantaneous jet mixing (completed in milliseconds) avoids batch variations caused by traditional droplet addition, making it suitable for continuous production. Therefore, the preparation system of this embodiment can prepare liposome polymer nanospheres with uniform particle size, solving the problem of uneven microsphere particle size that exists in the prior art when using microfluidic systems to prepare liposome polymer nanospheres.
[0151] By directly embedding the Laval nozzle 312 into the inlet channel, external pressurization equipment (such as a high-pressure pump) is eliminated, reducing pipeline connection points, lowering the risk of leakage, and improving system compactness. With at least two inlet channels, each corresponding to a specific inlet channel and positioned within it, flexible configurations of multiple inlet channels are possible. This allows for the simultaneous processing of various raw materials (such as lipid phases, aqueous phases, and drug solutions), adapting to complex formulation requirements.
[0152] The Laval Nozzle 312 utilizes fluid pressure energy to convert it into kinetic energy, making it more energy-efficient than mechanical stirring and reducing maintenance costs due to the absence of moving parts and wear. The improved mixing efficiency also reduces the amount of surfactant needed, meeting the demands of low-cost pharmaceutical manufacturing. The jet mixing process generates no significant temperature rise, preventing the inactivation of heat-sensitive drugs (such as proteins), and the reduced metal contact area lowers the risk of heavy metal contamination.
[0153] Furthermore, the design of the Laval nozzle 312 allows for precise control of the fluid flow state as needed. For example, the conversion between subsonic and supersonic flow can be achieved by changing the geometric parameters of the Laval nozzle 312 (such as throat diameter, inlet and outlet cross-sectional area ratio, etc.). Through precise control, the jet mixer 310 can optimize the jet velocity and turbulence intensity, thereby optimizing the mixing and formation process of liposome polymer nanospheres. The expanding section of the Laval nozzle 312 helps alleviate the back pressure generated by the high-speed jet. Typically, high-speed jets in a mixer lead to an increase in local pressure, thus affecting the flow of subsequent fluids and mixing efficiency. Through the gradually expanding section design of the Laval nozzle 312, the back pressure can be eliminated to a certain extent, resulting in smoother fluid flow and more uniform mixing. Therefore, the preparation system of this embodiment can produce liposome polymer nanospheres with uniform particle size.
[0154] Furthermore, the collision mixing unit 311 comprises one outlet channel and two inlet channels; the outlet channel and the two inlet channels are arranged circumferentially around the collision mixing unit 311; the two inlet channels are symmetrically arranged along the central axis of the outlet channel. The symmetrical circumferential distribution and symmetrical arrangement of the two inlet channels along the central axis of the outlet channel allow the high-speed jet to collide head-on within the mixing chamber, generating stronger turbulence and shear force, significantly improving the dispersion uniformity of lipids and polymers. The outlet channel and the inlet channel are at a certain angle, allowing for rapid removal of the mixed product, preventing the retention of insufficiently mixed materials, and ensuring the stability of continuous flow. The circumferential layout shortens the path of the jet from inlet to collision, reducing pressure loss and lowering energy consumption compared to a straight channel. The symmetrical inlet channels balance the jet pressure, avoiding uneven mixing caused by unilateral flow deviation. By independently controlling the flow rates of the two inlet jets, gradient mixing can be achieved, adapting to complex process requirements. The circumferential liquid outlet design shortens the residence time of the product in the cavity.
[0155] Furthermore, the expansion ratio of the expansion section of the Laval nozzle 312 is 2 to 3. This design not only directly affects the maximum Mach number that the flow velocity inside the Laval nozzle 312 can reach, but also affects the distribution of the Mach number and the stability of axial Mach number and velocity variations. At this point, the flow field inside the Laval nozzle 312 can achieve relatively good results. The greater the deviation of the expansion ratio from this range, the worse the overall flow field quality.
[0156] Preferably, the expansion ratio of the expansion section of the Laval nozzle 312 is 2 or 3.
[0157] It should be noted that the expansion ratio of the expansion section of the Laval nozzle 312 used for jet oil phase can be the same as or different from the expansion ratio of the expansion section of the Laval nozzle 312 used for jet water phase.
[0158] It is understandable that the expansion ratio of the expansion section of the Laval nozzle 312 is the ratio of the area of the cross-section at the exit of the expansion section to the area of the minimum cross-section at the throat of the Laval nozzle 312.
[0159] Understandably, the section of the Laval nozzle 312 closest to the mixing chamber is the expansion section, the section furthest from the mixing chamber is the contraction section, and the area between the expansion and contraction sections is the throat.
[0160] like Figure 13 As shown, in some embodiments, the liposome polymer nanosphere preparation system based on Laval nozzle impact jet technology further includes an oil phase supply device 320 and an aqueous phase supply device 330; the oil phase supply device 320 is used to store the oil phase; the oil phase supply device 320 is connected to the inlet of a Laval nozzle 312; the aqueous phase supply device 330 is used to store the aqueous phase; the aqueous phase supply device 330 is connected to the inlet of another Laval nozzle 312. By setting up the oil phase supply device 320 and the aqueous phase supply device 330, continuous production can be achieved, improving production efficiency.
[0161] Furthermore, the oil phase supply device 320 includes at least two oil phase storage tanks; the two oil phase storage tanks are connected to the inlet of a Laval nozzle via a first three-way valve. After the oil phase in one of the oil phase storage tanks is used up, the oil phase in the other oil phase storage tank can be supplied to the inlet of the Laval nozzle by switching the first three-way valve.
[0162] Furthermore, the aqueous phase supply device 330 includes at least two aqueous phase storage tanks; the two aqueous phase storage tanks are connected to the inlet of another Laval nozzle via a second three-way valve. After the oil phase in one of the aqueous phase storage tanks is used up, the oil phase in the other aqueous phase storage tank can be supplied to the inlet of the Laval nozzle by switching the second three-way valve.
[0163] In a fifth typical embodiment of the present invention, a specific embodiment of the present invention also provides a method for preparing liposome polymer nanospheres based on Laval nozzle collision jet technology. This preparation method employs the liposome polymer nanosphere preparation system based on Laval nozzle collision jet technology described in any of the above embodiments. The preparation method includes: supplying an oil phase to one Laval nozzle 312 and a water phase to another Laval nozzle 312; the oil phase and water phase forming a high-speed jet through the corresponding Laval nozzle 312; the two high-speed jets colliding and mixing in a mixing chamber to obtain liposome polymer nanospheres.
[0164] Furthermore, the flow rate of the oil phase is 5-7 mL / min, and the flow rate of the aqueous phase is 15-20 mL / min.
[0165] Furthermore, the mixing time is 2-5 minutes.
[0166] Furthermore, the inlet pressure of both Laval nozzles in the liposome polymer nanosphere preparation system based on Laval nozzle impact jet technology is controlled between 0.1 and 15 MPa.
[0167] Preferably, the inlet pressure of both Laval nozzles in the liposome polymer nanosphere preparation system based on Laval nozzle impact jet technology is controlled at 1-1.5 MPa.
[0168] In a sixth typical embodiment of the present invention, the present invention also provides a method for preparing the above-mentioned environmental control bilayer composite microbial scavenging microspheres, comprising the following steps: mixing water, nano-disinfecting microspheres and a stabilizer to prepare a continuous phase; mixing an organic solvent and polylactic acid to prepare a dispersed phase; forming an emulsion from the continuous phase and the dispersed phase; stirring, evaporating the solvent and freeze-drying the emulsion to obtain the environmental control bilayer composite microbial scavenging microspheres.
[0169] The present invention discloses a method for preparing environmental control bilayer composite microbial scavenging microspheres, comprising the preparation of a continuous phase and a dispersed phase, the operation of a microsphere preparation system, and subsequent processing steps. This method enables precise control of the microsphere preparation process, ensuring uniform mixing and formation of the core and shell.
[0170] According to some specific embodiments of the present invention, the preparation method of the environmental control bilayer composite microbial scavenging microspheres is based on the liposome polymer microsphere preparation system in the second typical embodiment and is carried out using the liposome polymer microsphere preparation method in the third typical embodiment, specifically including the following steps: The continuous phase and the dispersed phase are respectively injected into the inner and outer channels of the liposome polymer microsphere preparation system; a protective gas is introduced into the outer channel to push the dispersed phase through the micropores of the liposome polymer microsphere preparation system, forming droplets in the inner channel and mixing with the continuous phase to form an emulsion; After emulsification is complete, the emulsion in the inner flow channel is stored. The emulsion was stirred, the solvent was evaporated, and the emulsion was freeze-dried to obtain environmental control bilayer composite microbial scavenging microspheres.
[0171] By injecting the continuous phase and dispersed phase into the inner and outer channels of liposome polymer microspheres, respectively, and then introducing a protective gas to drive the dispersed phase to form droplets that mix with the continuous phase, the emulsification process can be effectively controlled, resulting in a uniform and stable emulsion. Subsequent stirring, solvent evaporation, and freeze-drying steps further remove the solvent, allowing the microspheres to solidify and form a high-performance environmental control bilayer composite microbial scavenging microsphere. This preparation method ensures the consistency of microsphere quality and performance, improves production efficiency and product stability, enabling large-scale production and application in practical disinfection scenarios.
[0172] According to some specific embodiments of the present invention, the nano-sterilization microspheres of the present invention can be prepared independently using conventional microsphere preparation systems and methods in the art, such as emulsification, suspension polymerization, seeding, microfluidics, solvothermal methods, nanosphere etching, ultrasonic spray pyrolysis, membrane emulsification, crosslinking, and spray drying.
[0173] According to some specific embodiments of the present invention, the preparation method of the nano-sterilization microspheres is based on the liposome polymer nanosphere preparation system based on Laval nozzle impact jet technology in the fourth typical embodiment of the present invention, and is carried out using the liposome polymer nanosphere preparation method based on Laval nozzle impact jet technology in the fifth typical embodiment of the present invention, specifically including the following steps: Hydrogenated lecithin, distearate phosphatidylcholine, and cholesterol were mixed to prepare an oil phase; polyethyleneimine, polyhexamethylene biguanide, and benzalkonium chloride were mixed to prepare an aqueous phase. The oil phase is delivered to one Laval nozzle of the liposome polymer nanosphere preparation system based on Laval nozzle collision jet technology, and the aqueous phase is delivered to another Laval nozzle. The oil phase and the aqueous phase form a high-speed jet through the corresponding Laval nozzles in the liposome polymer nanosphere preparation system based on Laval nozzle collision jet technology. The two high-speed jets collide and mix in the mixing chamber of the liposome polymer nanosphere preparation system based on Laval nozzle collision jet technology to obtain the nano-sterilized microspheres.
[0174] The aforementioned method for preparing nano-sterilizing microspheres includes the preparation of an oil phase and an aqueous phase, as well as a mixing process within a liposome polymer nanosphere preparation system based on Laval nozzle collision jet technology. By separately feeding the oil and aqueous phases into a Laval nozzle to form a high-speed jet, and then colliding and mixing them in the mixing chamber, the two phases can be fully contacted and reacted to form uniform nano-sterilizing microspheres. This preparation method allows for precise control of the particle size and composition distribution of the nano-sterilizing microspheres, improving their quality and performance. Uniform nano-sterilizing microspheres can better exert their sterilization effect and also help improve the quality and performance of subsequent environmentally controlled sterilization microsphere preparations, ensuring the sterilization effect and long-lasting effect of the final product.
[0175] The control parameters in the liposome polymer nanosphere preparation system based on Laval nozzle impact jet technology used in the following examples and comparative examples are as follows: the expansion ratio of the expansion section of the Laval tube is 3.
[0176] The control parameters of the liposome polymer microsphere preparation system are as follows: the pore size of micropore 214 is 5 micrometers, and the base angle α of the reflective axial pyramid is 2°. The base angle α of the reflective axial pyramid is 3°.
[0177] Example 1 This embodiment provides an environmental control bilayer composite microbial scavenging microsphere, comprising a core and a shell encapsulating the core. The core is prepared from water, nano-sterilization microspheres, and a stabilizer. The shell is prepared from dichloromethane and polylactic acid. The stabilizer is polyvinyl alcohol with a weight average molecular weight of 10,000, and the amount of stabilizer accounts for 1% of the mass percentage of the core preparation materials. The amount of polylactic acid accounts for 5% of the mass volume percentage of the shell preparation materials. The weight average molecular weight of polylactic acid is 50,000-100,000.
[0178] The nano-sterilization microspheres are prepared from oil-phase and aqueous-phase raw materials. The oil-phase raw materials include hydrogenated lecithin, distearate phosphatidylcholine, and cholesterol; the molar ratio of hydrogenated lecithin, distearate phosphatidylcholine, and cholesterol is 50:10:40. The aqueous-phase raw materials include polyethyleneimine, polyhexamethylene biguanide, and benzalkonium chloride. The weight-average molecular weight of polyethyleneimine is 3000. The mass ratio of polyethyleneimine, polyhexamethylene biguanide, and benzalkonium chloride is 2.5:2.5:5. The volume ratio of oil-phase raw materials to aqueous-phase raw materials is 1:3.
[0179] This embodiment also provides a method for preparing the environmental control bilayer composite microbial scavenging microspheres, including the following steps: Hydrogenated lecithin, distearate phosphatidylcholine, and cholesterol were mixed to prepare an oil phase; polyethyleneimine, polyhexamethylene biguanide, and benzalkonium chloride were mixed to prepare an aqueous phase. An oil phase was supplied to one Laval nozzle of a liposome polymer nanosphere preparation system based on Laval nozzle collision jetting technology, while an aqueous phase was supplied to the other. The oil and aqueous phases formed high-speed jets through their respective Laval nozzles in the system. These two high-speed jets collided and mixed in the mixing chamber of the system to obtain sterile nanospheres. The inlet pressure of the two Laval nozzles was controlled at approximately 1.5 MPa, the aqueous phase flow rate was controlled at 18 mL / min, the oil phase flow rate was controlled at 6 mL / min, and the mixing time was 5 min. Transmission electron microscopy (TEM) images of the sterile nanospheres are shown below. Figure 16 As shown, its particle size is 131.5±3.8nm and PDI is 0.09.
[0180] Water, nano-sterilization microspheres, and stabilizers were stirred and mixed at 600 rpm to prepare a continuous phase; dichloromethane and polylactic acid were mixed and dissolved until completely transparent to prepare a dispersed phase.
[0181] The air pump delivers protective gas into the first dispersed phase storage unit of the dispersed phase supply device, injecting the dispersed phase from the first dispersed phase storage unit into the outer channel of the membrane emulsification device, filling the outer channel with dispersed phase. The circulation power source is then activated, and the continuous phase stored in the second continuous phase storage unit is drawn into the inner channel, forming a continuous phase circulation loop. By adjusting the conduction state of the sixth three-way valve, the gas path is switched, allowing protective gas to enter the outer channel, increasing the pressure in the outer channel to 0.02 MPa. This causes the dispersed phase to permeate through the micropores to form droplets, and the continuous phase in the inner channel scours and disperses the droplets into the continuous phase to form an emulsion.
[0182] After emulsification, the emulsion in the inner channel is stored, then stirred, the solvent is evaporated and freeze-dried. The dried microspheres are then subjected to high-temperature complexation at 90°C for 60 minutes to obtain environmental control double-layer composite microbial scavenging microspheres.
[0183] The obtained scanning electron microscope image of the environmental control bilayer composite microbial scavenging microspheres is shown below. Figure 6 As shown, its particle size is 11.5±1.7μm.
[0184] Example 2 This embodiment provides an environmental control bilayer composite microbial scavenging microsphere, which differs from Example 1 only in that the weight-average molecular weight of polyethyleneimine is 6000. The resulting environmental control bilayer composite microbial scavenging microsphere has a particle size of 12.1 ± 1.2 μm.
[0185] Example 3 This embodiment provides an environmental control bilayer composite microbial scavenging microsphere, which differs from Example 1 only in that the weight-average molecular weight of polyethyleneimine is 18,000. The resulting environmental control bilayer composite microbial scavenging microsphere has a particle size of 12.4 ± 0.9 μm.
[0186] Example 4 This embodiment provides an environmental control bilayer composite microbial scavenging microsphere, which differs from Example 1 only in that the weight-average molecular weight of polyethyleneimine is 25,000. The resulting environmental control bilayer composite microbial scavenging microsphere has a particle size of 11.6 ± 1.9 μm.
[0187] Experimental Example 1. Nano-sterilization microspheres (named microsphere 600, microsphere 1800, microsphere 3000, microsphere 6000, microsphere 18000, microsphere 25000, microsphere 50000, and microsphere 100000, respectively) prepared using PEI with different molecular weights (600, 1800, 3000, 6000, 18000, 25000, 50000, and 100000, respectively) as raw materials were prepared with water to form a 0.05% nano-sterilization solution. This solution was applied to RT-PCR experiments. Seven days after the disinfectant was sprayed, African swine fever (ASFV) virus was coated onto the microspheres. The nucleic acid results are shown in Table 1 below. NA in the table indicates low viral load or no viral load.
[0188] Table 1
[0189] The experimental results in Table 1 show that PEI nanospheres prepared with a molecular weight range of 3000-25000 have advantages in terms of disinfection effect and durability.
[0190] 2. Nano-disinfectant solutions prepared using PEI with different molecular weights (3000, 6000, 18000, and 25000, respectively) as raw materials, and environmental control bilayer composite microbial removal microspheres from Examples 1-4 were respectively mixed with water to prepare 0.05% disinfectant. These were then applied to RT-PCR experiments. After 30 days of disinfectant spraying, African swine fever (ASFV) virus was coated onto the surface. The nucleic acid results are shown in Table 2 below.
[0191] Table 2
[0192] As shown in Table 2, the uncoated nanospheres exhibited poor inhibitory effects against African swine fever (ASFV) virus after 30 days, and viral nucleic acid was detectable. In contrast, the environmental control bilayer composite microbial scavenging microspheres prepared using PEI with a specific molecular weight (3000-6000) and coated with a shell, maintained a high inhibitory effect against ASFV virus after 30 days. This indicates that the environmental control bilayer composite microbial scavenging microspheres of this invention have superior long-term disinfection efficacy and durability.
[0193] 3. Nano-disinfectant solutions prepared using PEI with different molecular weights (3000, 6000, 18000, and 25000, respectively) as raw materials, and environmental control bilayer composite microbial removal microspheres from Examples 1-4 were respectively mixed with water to prepare 0.05% disinfectant. These were then applied to RT-PCR experiments. Thirty days after the disinfectant was sprayed, influenza H1S1 virus was coated on the surface, and the nucleic acid results are shown in Table 3 below.
[0194] Table 3
[0195] As shown in Table 3, the uncoated nano-disinfectant solution exhibited poor inhibitory effects against the H1S1 influenza virus after 30 days, and viral nucleic acid could be detected. In contrast, the environmental control bilayer composite microbial scavenging microspheres prepared using PEI with a specific molecular weight (3000-6000) of this invention, which encapsulate the nano-disinfectant microspheres, still showed high inhibitory effects against the H1S1 influenza virus after 30 days. This indicates that the environmental control bilayer composite microbial scavenging microspheres of this invention have superior long-term disinfection effects and durability.
[0196] 4. Nano-disinfecting microspheres prepared using PEI with different molecular weights (3000 and 6000, respectively) as raw materials, and environmental control bilayer composite microbial removal microspheres from Examples 1-2, were respectively diluted with water to prepare 0.05% disinfectant solutions. These solutions were then applied to RT-PCR experiments. Seven days after disinfectant spraying, influenza H1S1 virus or ASFV virus was coated onto the microspheres. The nucleic acid results for influenza H1S1 virus are shown in Table 4, and the nucleic acid results for ASFV virus are shown in Table 5. Thirtieth day after disinfectant spraying, influenza H1S1 virus or ASFV virus was coated onto the microspheres again. The nucleic acid results for influenza H1S1 virus are shown in Table 6, and the nucleic acid results for ASFV virus are shown in Table 7.
[0197] Table 4
[0198] Table 5
[0199] Table 6
[0200] Table 7
[0201] As can be seen from the experimental results in Tables 4-7, compared with nano-sterilization microspheres without a shell, the environmental control sterilization microspheres of the present invention have a better and longer-lasting sterilization effect on influenza H1S1 virus or ASFV virus, and can still completely kill influenza H1S1 virus and ASFV virus after 30 days.
[0202] 5. Prepare 0.05% disinfectant by adding water to the environmental control double-layer composite microbial removal microspheres of Examples 1-2, and apply them to the sterilization experiments of Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. The experimental method is as follows: (1) Take 1 ml of disinfectant solution and spread it on a solid culture medium, and seal it with sealing film; (2) On the 7th day and the 30th day, respectively, 100 μl of Escherichia coli (10 6 CFU was spread onto a solid culture medium, incubated overnight, photographed, counted, and analyzed. The experimental results are as follows: Figure 17 As shown, the environmental control double-layer composite microbial removal microspheres of the present invention can still completely kill Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli after 30 days.
[0203] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims
1. A bilayer composite microbial scavenging microsphere for environmental control, characterized in that, It includes a core and a shell enclosing the core. The raw materials for preparing the core include water, nano-sterilized microspheres, and stabilizers. The raw materials for preparing the shell include organic solvents and polylactic acid. The nano-sterilization microspheres are prepared from oil-phase raw materials and aqueous-phase raw materials; the oil-phase raw materials include hydrogenated lecithin, distearate phosphatidylcholine and cholesterol; the aqueous-phase raw materials include polyethyleneimine, polyhexamethylene biguanide and benzalkonium chloride.
2. The environmental control bilayer composite microbial scavenging microspheres according to claim 1, characterized in that, The molar ratio of the hydrogenated lecithin, the distearate phosphatidylcholine and the cholesterol is (45~55):(8~12):(35~45).
3. The environmental control bilayer composite microbial scavenging microspheres according to claim 1 or 2, characterized in that, The mass ratio of the polyethyleneimine, the polyhexamethylene biguanide, and the benzalkonium chloride is (0.5~3):(1~5):(2~8). And / or, the volume ratio of the oil phase raw material to the aqueous phase raw material is 1:(2~4).
4. The environmental control bilayer composite microbial scavenging microspheres according to claim 1, characterized in that, The weight-average molecular weight of the polyethyleneimine is 2000-30000.
5. The environmental control bilayer composite microbial scavenging microspheres according to claim 1, characterized in that, The amount of the stabilizer is 1-2% of the mass of the raw materials used to prepare the core. And / or, the stabilizer is polyvinyl alcohol or hexadecyltrimethylammonium bromide; the weight-average molecular weight of the polyvinyl alcohol is 5000~15000.
6. The environmental control bilayer composite microbial scavenging microspheres according to claim 1, characterized in that, The amount of polylactic acid used accounts for 5% to 10% of the mass volume percentage of the raw materials used to prepare the outer shell; And / or, the polylactic acid has a weight-average molecular weight of 20,000 to 200,000; And / or, the organic solvent is selected from one or more of dichloromethane, chloroform, benzene, acetone, dimethyl sulfoxide, and ethanol.
7. The environmental control bilayer composite microbial scavenging microspheres according to claim 1, characterized in that, The particle size of the environmental control bilayer composite microbial removal microspheres is 8~15μm, and the particle size of the nano-disinfection microspheres is 100~150nm.
8. The method for preparing the environmental control bilayer composite microbial scavenging microspheres according to any one of claims 1-7, characterized in that, Includes the following steps: A continuous phase was prepared by mixing water, nano-sterilization microspheres, and a stabilizer; a dispersed phase was prepared by mixing an organic solvent and polylactic acid; the continuous phase and the dispersed phase were mixed to form an emulsion; the emulsion was stirred, the solvent was evaporated, and the emulsion was freeze-dried to obtain environmental control bilayer composite microbial scavenging microspheres.
9. The method for preparing the environmental control bilayer composite microbial scavenging microspheres according to claim 8, characterized in that, The method for preparing the environmental control bilayer composite microbial scavenging microspheres is based on a liposome polymer microsphere preparation system and specifically includes the following steps: The continuous phase and the dispersed phase are respectively injected into the inner and outer channels of the liposome polymer microsphere preparation system; a protective gas is introduced into the outer channel to push the dispersed phase through the micropores of the liposome polymer microsphere preparation system, forming droplets in the inner channel and mixing with the continuous phase to form an emulsion; After emulsification is complete, the emulsion in the inner flow channel is stored. The emulsion was stirred, the solvent was evaporated, and the mixture was freeze-dried to obtain environmental control and disinfection microspheres.
10. The method for preparing the environmental control bilayer composite microbial scavenging microspheres according to claim 8 or 9, characterized in that, The method for preparing the nano-sterilization microspheres employs a liposome polymer nanosphere preparation system based on Laval nozzle impact jet technology, and specifically includes the following steps: Hydrogenated lecithin, distearate phosphatidylcholine, and cholesterol were mixed to prepare an oil phase; polyethyleneimine, polyhexamethylene biguanide, and benzalkonium chloride were mixed to prepare an aqueous phase. The oil phase is delivered to one Laval nozzle of the liposome polymer nanosphere preparation system based on Laval nozzle collision jet technology, and the aqueous phase is delivered to another Laval nozzle. The oil phase and the aqueous phase form a high-speed jet through the corresponding Laval nozzles in the liposome polymer nanosphere preparation system based on Laval nozzle collision jet technology. The two high-speed jets collide and mix in the mixing chamber of the liposome polymer nanosphere preparation system based on Laval nozzle collision jet technology to obtain the nano-sterilized microspheres.