Method for preparing delayed drug based on microdroplet template limited domain assisted self-assembly

Abstract

The application is a preparation method of a delay composition based on microdroplet template limited domain assisted self-assembly. The method comprises the following steps: (1) preparing a continuous phase solution: weighing a surfactant and dissolving it in deionized water to obtain a continuous phase solution; (2) preparing a dispersed phase solid-liquid system containing delay composition ingredient particles: weighing a binder and dissolving it in an ethyl acetate solvent to obtain a dispersed phase solution; weighing any one of tungsten-based, boron-based, silicon-based, silicon-iron-based, titanium-based, zirconium-based and molybdenum-based delay composition and adding it to the dispersed phase solution to obtain a dispersed phase solid-liquid system containing delay composition ingredient particles; (3) preparing a delay composition composite particle based on a microdroplet template generation device. The application uses a microdroplet template limited domain assisted self-assembly method to prepare a delay composition based on microfluidic technology, improves the delay precision of the delay composition, and solves the sedimentation problem of solid particles in a conventional microchannel.

Description

Technical Field

[0001] The present invention belongs to the field of energetic materials, and in particular relates to a method for preparing a delay spray based on micro-droplet template confinement-assisted self-assembly. Background Art

[0002] Delay charge is a composite energetic material that leverages its constant burning rate and stable combustion characteristics to provide a precise delay time for a detonation or ignition sequence. It is widely used in pyrotechnic devices such as time fuses, self-destruct mechanisms, release mechanisms, delay detonators, and delayed ignition devices to achieve functions such as delayed detonation, micro-difference blasting, or delayed ignition of the next level of pyrotechnic devices. Due to its special role in pyrotechnic devices, although its usage in pyrotechnic devices is very small, its quality requirements are high. Traditional methods for preparing delay charge include mechanical mixing, manual mixing, and chemical co-precipitation. However, the mixing effects of these methods are all limited by macroscopic spatial scale conditions, which gradually leads to a bottleneck in improving the delay accuracy. Therefore, a new technology and method that can break free from the limitations of macroscopic conditions is urgently needed to achieve ultra-uniform mixing of composite energetic materials.

[0003] Self-assembly systems involve the synergistic interaction of weak, non-directional, non-covalent bonds, such as hydrogen bonds, van der Waals forces, and weak ionic bonds, linking atoms, ions, molecules, or nanomaterials. This allows these building blocks to spontaneously organize or aggregate into stable, geometrically regular structures. A key characteristic of the self-assembly process is that once initiated, it automatically proceeds to a desired endpoint, with the molecules and other building blocks automatically arranging themselves into an ordered pattern. Self-assembly methods have been relatively understudied in the preparation of composite energetic materials. For energetic materials, such as composite materials, which often require the formation of ordered, large-scale structures, the coordinated self-assembly of macromolecules and nanoparticles can achieve a controlled, ordered distribution of nanoparticles, effectively improving the uniformity of mixing within the composite energetic material within the large-scale structure. One essential step in the self-assembly of large-scale structures is identifying a template of suitable shape and size. This template, as the primary matrix for forming the ordered structure, is a crucial prerequisite for the preparation of large-scale, structurally controllable self-assembled structures.

[0004] Microfluidics is a system technology for microfluidics composed of microchannels and microstructures on the micrometer scale, with functionality and the ability to accomplish specific tasks. It is characterized by continuous flow and primarily manifests itself in microfluidic chips. Common microfluidic chip configurations include T-shaped, Y-shaped, and cross-shaped ones. However, these simple reactor configurations are no longer able to meet the growing experimental needs of researchers. Consequently, researchers have developed a variety of microreactors for droplet dispersion based on these configurations, including microporous devices. Microporous devices have proven to be effective microdispersors in various fields. Researchers have used microporous array chips to prepare spherical polymer particles with good monodispersity, narrow particle size distribution, and adjustable microstructure. These studies provide new insights into the generation of self-assembly templates for large-scale structures. Summary of the Invention

[0005] The purpose of the present invention is to provide a method for preparing a delay spray based on micro-droplet template confinement-assisted self-assembly.

[0006] The technical solution to achieve the purpose of the present invention is: a method for preparing a delay spray based on micro-droplet template confinement-assisted self-assembly, comprising the following steps:

[0007] Step (1): preparing a continuous phase solution: weighing either sodium dodecyl sulfate or sodium dodecylbenzenesulfonate as a surfactant and dissolving it in deionized water to obtain a continuous phase solution;

[0008] Step (2): preparing a dispersed phase solid-liquid system containing particles of the delay drug formula component: weighing any one of shellac or nitrocellulose as a binder and dissolving it in ethyl acetate solvent to obtain a dispersed phase solution; weighing any one of the delay drug formulas of tungsten, boron, silicon, ferrosilicon, titanium, zirconium, and molybdenum to add to the dispersed phase solution to obtain a dispersed phase solid-liquid system containing particles of the delay drug formula component;

[0009] Step (3): preparing delay drug composite particles based on a micro-droplet template generating device: the micro-droplet template generating device includes a stainless steel-based microporous array chip and a micro-sieve disperser for fixing the chip; a dispersed phase solid-liquid system containing delay drug formula component particles uniformly mixed by ultrasound flows into the micro-sieve disperser; the dispersed phase solid-liquid system reaches the top of the stainless steel-based microporous array chip through the fluid channel in the micro-sieve disperser; the continuous phase solution reaches the bottom of the stainless steel-based microporous array chip through the fluid channel in the micro-sieve disperser; after the dispersed phase solid-liquid system passes through the stainless steel-based microporous array chip, it is sheared by the continuous phase solution to form micro-droplets, and the delay drug solid particles in the micro-droplets immediately start a self-assembly process to obtain delay drug composite particles.

[0010] Furthermore, the concentration of the surfactant in step (1) is in the range of 0.5% to 2%.

[0011] Furthermore, the concentration of the binder dissolved in the dispersed phase solution in step (2) is in the range of 0.5% to 5%.

[0012] Furthermore, in step (2), the solid content of the delay drug formulation component particles in the dispersed phase solution is in the range of 25 to 100 mg / mL.

[0013] Furthermore, the flow rate of the continuous phase solution in step (3) is 5 to 40 mL / min.

[0014] Furthermore, the ultrasonic frequency of the ultrasonic uniform mixing in step (3) is 10 to 30 kHz.

[0015] Furthermore, the dimensions of the stainless steel-based micropore array chip used in step (3) are specifically as follows: length 25±0.1 mm, width 20±0.1 mm, thickness 1±0.1 mm, number of micropores 20-30, micropores arranged in regular rows and columns, and the micropore diameter is the same, 0.8±0.01 mm.

[0016] Furthermore, the micro-droplet template generation device used in step (3) also includes a high-pressure constant-flow infusion pump for driving the continuous phase solution, an ultrasonic crusher and a liquid holding container for ultrasonicating the dispersed phase solid-liquid system, a glass surface dish for collecting the delay drug composite particles flowing out of the micro-sieve disperser, a droplet online monitoring module for photographing the shape and size of the droplets formed in the micro-sieve disperser; and a connecting assembly for connecting the various components.

[0017] Furthermore, the droplet online monitoring module also includes a bottom light source for illumination and a high-speed camera located below the glass watch glass;

[0018] The ultrasonic crusher is also equipped with a controller. The dispersed phase solid-liquid system containing the particles of the delayed drug formula components is placed in a liquid holding container. The dispersed phase solid-liquid system containing the particles of the delayed drug formula components is ultrasonicated through the high-frequency vibration of the controller and the ultrasonic crusher.

[0019] Furthermore, the connection assembly includes a connecting pipe and a stainless steel ferrule ball valve;

[0020] The bottom of the liquid holding container is connected to a micro-sieve disperser through a stainless steel sleeve ball valve.

[0021] Compared with the prior art, the present invention has the following significant advantages:

[0022] 1. The combination of a liquid holding container and an ultrasonic disruptor solves the sedimentation problem of solid particles in conventional microchannels. By controlling the ultrasonic frequency, the flow of solid composite particles with high density and obvious gravity, such as those with delayed drug flow, in the microreactor is achieved.

[0023] 2. Self-assembly process based on microdroplet template confinement. The binder, typically a polymer containing multiple reactive groups, utilizes this structural property to uniformly assemble the delay agent components into microparticles. The delay agent suspension in the liquid holding vessel enters the microdroplet template generation module simultaneously with ultrasonic high-frequency dispersion. Due to shear induction in the continuous phase and the interfacial tension between the ethyl acetate and water phases, suspended droplets containing the delay agent form within the continuous phase. Since ethyl acetate is slightly soluble in water, after droplet formation, ethyl acetate diffuses into the water through the interphase interface. Simultaneously, water also penetrates the droplet through the interphase interface. This diffusion of ethyl acetate into water gradually increases the concentration of the binder dissolved in ethyl acetate to supersaturation, leading to nucleation and crystallization. Non-covalent forces, such as van der Waals forces and hydrogen bonds, gradually form between the molecules on the surface of the binder crystals. Simultaneously, the surface tension of the liquid maintains the droplet's spherical shape. This creates a spherical network of forces between the binder molecules, while the delay agent components are uniformly dispersed among them. As the solvent exchange process progresses, the droplet size gradually shrinks, the number of binder crystals increases, the number of non-covalent bonds increases, and the stability of the spherical network force system increases. Ultimately, while maintaining good dispersion, the delay agent components are tightly wrapped in a spherical network force system through the coupling of liquid surface tension and intermolecular forces, completing the self-assembly process. This method has a higher mixing uniformity than traditional mixing methods, which can further improve the delay agent's delay accuracy.

[0024] 3. By changing parameters such as the binder type, binder concentration, and continuous phase solution flow rate, the morphology of the delay agent composite particles obtained based on the microdroplet template confinement-assisted self-assembly process can be made to tend towards spheres of uniform size. The spherical composite energetic material can improve the fluidity of the agent and thus enhance the charging performance.

[0025] 4. This system can be used to quickly screen and optimize preparation conditions, and experimental conditions are easy to adjust.

[0026] 5. The system can achieve batch preparation of supermixed delayed release drugs by parallel connection of ultrasonic mixing module and microdroplet template generation module. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 Schematic diagram of the delayed release drug preparation system based on micro-droplet template confinement-assisted self-assembly in this application.

[0028] Figure 2 Schematic diagram of droplet generation for this application.

[0029] Figure 3 This is a schematic diagram of the process of preparing a supermixed boron / barium chromate delay agent based on the microdroplet template confinement assisted self-assembly method in Example 1 of the present application.

[0030] Figure 4 This is a morphology diagram of the super mixed boron / barium chromate delay spray particles obtained in Example 1 of the present application.

[0031] Figure 5 This is a comparison of the thermal performance curves of the supermixed boron / barium chromate delay agent obtained in Example 1 of the present application and the boron / barium chromate delay agent prepared by conventional manual stirring; wherein (a) is conventional manual stirring, and (b) is Example 1.

[0032] Figure 6 This is a combustion process diagram of the super mixed boron / barium chromate delay powder obtained in Example 1 of the present application.

[0033] Description of reference numerals:

[0034] 1- High-pressure constant-flow infusion pump, 2- Continuous phase solution, 3- Ultrasonic crusher, 4- Liquid holding container, 5- Dispersed phase solid-liquid system containing particles of delayed-release drug formulation, 6- Stainless steel-based microporous array chip, 7- Micro-mesh disperser, 8- Glass watch glass, 9- Delay-release drug composite particles, 10- Ultrasonic crusher controller, 11- High-speed camera. DETAILED DESCRIPTION

[0035] The present invention is further described in detail below with reference to the accompanying drawings.

[0036] like Figure 1 As shown, the present invention provides a delay drug preparation system based on the micro-droplet template confinement assisted self-assembly method, including a continuous phase driving module, an ultrasonic mixing module, a micro-droplet template generation module, a sample collection module, a droplet online monitoring module and a connection component.

[0037] Among them, the continuous phase driving module includes a high-pressure constant-current infusion pump 1, which is used to drive the continuous phase solution 2 required for the experiment. By adjusting the flow rate of the high-pressure constant-current infusion pump 1, the continuous phase solution 2 can be accurately driven and flowed into the micro-droplet template generation module.

[0038] The ultrasonic mixing module includes an ultrasonic crusher 3 and its controller 10, as well as a liquid holding container 4. Through the high-frequency vibration of the ultrasonic crusher 3, the dispersed phase solid-liquid system 5 containing the particles of the delay drug formula components is ultrasonicated, so that the particles of the delay drug formula components are evenly distributed in the dispersed phase, paving the way for the process of preparing supermixed delay drugs based on microdroplet template confinement-assisted self-assembly.

[0039] The droplet online monitoring module includes a high-speed camera 11, a bottom light source for illumination, and corresponding computer control software. The computer control software can be used to observe the fluid channel at the bottom of the micro-droplet template generation module, and then the shape and size of the droplets formed in the micro-sieve disperser can be photographed.

[0040] The microdroplet template generation module comprises a stainless steel-based microporous array chip 6 and a micromesh disperser 7 for securing the chip. The dispersed solid-liquid system, uniformly mixed by the ultrasonic mixing module, flows through a 304 stainless steel ferrule ball valve into the micromesh disperser 7. After passing through the stainless steel-based microporous array chip 6, the dispersed solid-liquid system 5 containing the delay agent formulation particles is sheared by the continuous phase solution 2 to form microdroplets. The delay agent solid particles within the microdroplets then begin self-assembly and flow into a glass watch glass 8, the sample collection module. The self-assembly process ultimately completes within the glass watch glass 8, yielding delay agent composite particles 9.

[0041] The present invention provides a method for preparing a delay spray by ultra-uniform mixing using the above system, comprising the following specific steps:

[0042] Step 1: Prepare the continuous phase solution 2, i.e., weigh a certain amount of surfactant and dissolve it in deionized water until the surfactant is completely dissolved, and set aside;

[0043] Step 2: Weigh a certain amount of delay spray formula component granules and set aside;

[0044] Step 3, preparing a dispersed phase solution, that is, weighing a certain amount of binder and dissolving it in ethyl acetate solvent for later use;

[0045] Step 4: Add the dispersed phase solution and the delay drug formulation component particles into the liquid holding container 4 and ensure that it is well sealed;

[0046] Step 5: Turn on the high-speed camera 11 and the bottom light source in the droplet online monitoring module, and observe the fluid channel at the bottom of the micro-droplet template generation module through computer control software;

[0047] Step 6: Turn on the continuous phase driving module and allow the continuous phase solution 2 to flow into the micro-droplet template generation module through the high-pressure constant-current infusion pump 1;

[0048] Step 7: Turn on the ultrasound through the controller 10 of the ultrasonic crusher to ultrasonicate the dispersed solid-liquid system 5 containing the particles of the delay spray formulation;

[0049] Step 8: Open the 304 stainless steel ferrule ball valve. The high-frequency vibration of the ultrasonic disruptor 3 creates periodic disturbances in the liquid, allowing the dispersed solid-liquid system to flow out regularly and evenly. The microdroplet template generation module comprises a stainless steel-based microporous array chip 6 and a micromesh disperser 7 that secures the chip. The dispersed solid-liquid system, uniformly mixed by the ultrasonic mixing module, flows through the 304 stainless steel ferrule ball valve and into the micromesh disperser 7. The dispersed solid-liquid system 5 containing the delay agent formulation particles passes through the fluid channels within the micromesh disperser 7 to the top of the stainless steel-based microporous array chip 6. The continuous phase solution 2 passes through the fluid channels within the micromesh disperser 7 to the bottom of the stainless steel-based microporous array chip 6. After passing through the stainless steel-based microporous array chip 6, the dispersed solid-liquid system 5 containing the delay agent formulation particles is sheared by the continuous phase solution 2 to form microdroplets. The delay agent solid particles within the microdroplets then begin self-assembly and flow into a glass watch glass 8, the sample collection module. Finally, the self-assembly process is completed in the glass watch glass 8, and the delay spray composite particles 9 are obtained.

[0050] In step nine, the delay drug composite particles 9 obtained from the micro-droplet template generation module are collected into a sample collection module, washed, filtered, and dried to finally obtain the super-mixed delay drug.

[0051] The surfactant dissolved in deionized water is any one of sodium dodecyl sulfate and sodium dodecylbenzene sulfonate, and the dissolved concentration range is 0.5% to 2%; the weighed delay agent formula is any one of tungsten-based, boron-based, silicon-based, ferrosilicon-based, titanium-based, zirconium-based, and molybdenum-based delay agents; the binder dissolved in ethyl acetate solvent is any one of shellac and nitrocellulose, and the dissolved concentration range is 0.5% to 5%; the solid content of the delay agent formula component particles in the dispersed phase solution is in the range of 25 to 100 mg / mL; the continuous phase solution flow rate range is 5 to 40 mL / min, and the ultrasonic frequency range of the ultrasonic crusher controller is 10 to 30 kHz.

[0052] The following examples are only used to further illustrate the present invention and should not be construed as limiting the present invention. Example 1: Preparation of Supermixed Boron / Barium Chromate Delay Agent Based on Microdroplet Template Confinement Assisted Self-Assembly Method

[0053] The experimental process is as follows Figure 1As shown. 10 g of sodium dodecyl sulfate (SDS) was weighed and dissolved in 500 mL of deionized water to prepare a 2% aqueous SDS solution as continuous phase solution 2. 75 mg of boron powder (B) and 425 mg of barium chromate (BaCrO4) were weighed and added to 10 mL of 5% shellac in ethyl acetate to prepare a dispersed phase solid-liquid system 5 containing particles of the delay spray formulation ingredients and a solid content of 50 mg / mL. This suspension was then transferred to a liquid holding container 4. After the liquid holding container 4 is connected to the ultrasonic crusher 3, the continuous phase solution 2 and the dispersed phase solid-liquid system 5 containing the delay drug formulation component particles can be controlled respectively by the high-pressure constant-current infusion pump 1 and the high-frequency vibration of ultrasound. The flow rate of the high-pressure constant-current infusion pump 1 is set to 10 mL / min, and the ultrasonic frequency of the ultrasonic crusher controller is selected to be 20 kHz. After passing through the stainless steel-based microporous array chip 6 in the micro-mesh disperser 7, the self-assembly process begins and super-mixed B / BaCrO4 delay drug composite particles 9 are obtained and collected in a glass watch glass 8. Finally, the suspension containing the super-mixed B / BaCrO4 delay drug composite particles 9 is transferred to a vacuum filtration device and washed with deionized water. After drying in a vacuum oven at 60°C for 8 hours, dried super-mixed B / BaCrO4 delay drug composite particles 9 are obtained. Figure 3 Schematic diagram of the process for preparing supermixed B / BaCrO4 delay agent based on microdroplet template confinement-assisted self-assembly. Figure 4 This is the electron microscope image of the supermixed B / BaCrO4 delay agent prepared under these experimental conditions. Figure 5 B / BaCrO4 delay agent prepared by conventional manual stirring ( Figure 5 (a)) and the super mixed B / BaCrO4 delay agent prepared under the above experimental conditions ( Figure 5 (b) shows a comparison of thermal performance curves. The sample prepared by manual stirring released a cumulative heat of 2994 J / g, while the sample prepared using the microdroplet template confinement-assisted self-assembly method released a cumulative heat of 3943 J / g, which is much higher than the former. The sharp and single exothermic peak in its DSC curve reflects the excellent combustion results of the composite structure, proving that the particles in the microspheres are evenly dispersed and tightly bound, which is conducive to the mass and heat transfer between B and BaCrO4 in the reaction, thereby releasing a huge amount of heat. Figure 6 A combustion diagram of a supermixed B / BaCrO4 delay charge prepared under these experimental conditions shows that the burning surfaces remain essentially parallel throughout the combustion process, demonstrating the sustained and stable heat transfer and further demonstrating the uniform mixing of B and BaCrO4. The combustion diagram can be used to determine the charge burning rate. By measuring different samples with the same charge and testing conditions, the delay accuracy of the B / BaCrO4 delay charge prepared using the microdroplet template confinement-assisted self-assembly method was determined to be 3.44%, significantly higher than that prepared using manual stirring.

Claims

1. A method for preparing a delay spray based on micro-droplet template confinement-assisted self-assembly, characterized in that: The steps include: Step (1): preparing a continuous phase solution: weighing either sodium dodecyl sulfate or sodium dodecylbenzene sulfonate as a surfactant and dissolving it in deionized water to obtain a continuous phase solution; Step (2): preparing a dispersed phase solid-liquid system containing particles of the delay drug formula component: weighing any one of shellac or nitrocellulose as a binder and dissolving it in ethyl acetate solvent to obtain a dispersed phase solution; weighing particles of the delay drug formula component of any one of tungsten, boron, silicon, ferrosilicon, titanium, zirconium, and molybdenum to obtain particles of the delay drug formula component and adding them to the dispersed phase solution to obtain a dispersed phase solid-liquid system containing particles of the delay drug formula component; Step (3): preparing delay drug composite particles based on a micro-droplet template generating device: the micro-droplet template generating device includes a stainless steel-based microporous array chip and a micro-mesh disperser for fixing the chip; a dispersed phase solid-liquid system containing delay drug formulation particles uniformly mixed by ultrasound flows into the micro-mesh disperser; The dispersed phase solid-liquid system reaches the top of the stainless steel-based microporous array chip through the fluid channel in the micromesh disperser; The continuous phase solution passes through the fluid channel in the micro-mesh disperser and reaches the bottom of the stainless steel-based microporous array chip. After passing through the stainless steel-based microporous array chip, the dispersed phase solid-liquid system is sheared by the continuous phase solution to form microdroplets. The delay drug solid particles in the microdroplets then begin to self-assemble, forming delay drug composite particles. The dimensions of the stainless steel-based micropore array chip used in step (3) are as follows: length 25±0.1 mm, width 20±0.1 mm, thickness 1±0.1 mm, number of micropores 20-30, micropores arranged in regular rows and columns, and micropore diameters of the same size, 0.8±0.01 mm; The micro-droplet template generating device used in step (3) further includes a high-pressure constant-flow infusion pump for driving the continuous phase solution, an ultrasonic crusher and a liquid holding container for ultrasonicating the dispersed phase solid-liquid system, a glass surface dish for collecting the delay drug composite particles flowing out of the micro-mesh disperser, a droplet online monitoring module for photographing the morphology and size of the droplets formed in the micro-mesh disperser; and a connecting assembly for connecting the various components; The concentration of the surfactant in step (1) ranges from 0.5% to 2%; The concentration range of the binder dissolved in the dispersed phase solution in step (2) is 0.5% to 5%; The solid content of the delay drug formulation component particles in the dispersed phase solution in step (2) is in the range of 25 to 100 mg / mL; The flow rate of the continuous phase solution in step (3) is 5-40 mL / min; The ultrasonic frequency of the ultrasonic uniform mixing in step (3) is 10 to 30 kHz; The droplet online monitoring module also includes a bottom light source for illumination and a high-speed camera located below the glass watch glass; The ultrasonic crusher is also equipped with a controller. The dispersed phase solid-liquid system containing the particles of the delayed-release drug formulation is placed in a liquid holding container. The dispersed phase solid-liquid system containing the particles of the delayed-release drug formulation is ultrasonicated by the high-frequency vibration of the controller and the ultrasonic crusher. The connection components include connecting pipes and stainless steel ferrule ball valves; The bottom of the liquid holding container is connected to a micro-sieve disperser through a stainless steel sleeve ball valve.

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