Preparation method of multi-chamber microcapsule

Abstract

The invention discloses a preparation method of a multi-chamber microcapsule, which comprises the following steps: 1) mixing a water phase containing a surface modifier and an oil phase containing a non-polar solvent and a pesticide, and carrying out ultrasonic emulsification to obtain an emulsion as a soft template for preparing a nanocapsule; (2) adding an acid-base regulator and a polymer into the template solution to react, so as to obtain a primary product of the nanocapsule; 3) washing to remove the residual polymer and surfactant in the primary product of the nanocapsule to obtain the nanocapsule; and 4) dispersing the nanocapsule obtained in the step 3) in a solvent to obtain a dispersion liquid, then carrying out spray drying on the dispersion liquid, and preparing the multi-chamber microcapsule by taking the nanocapsule as a shell layer. According to the preparation method, the nanocapsule which is regular in morphology, uniform in particle size distribution and capable of loading multiple drugs can be simply and rapidly obtained; the generation of damaged particles, agglomeration and solid microspheres can be reduced; the particle size of the multi-chamber microcapsule prepared by the preparation method is 500 nm to 10 [mu] m.

Description

Technical Field

[0001] The present invention relates to the technical field of microcapsule preparation. More specifically, it relates to a method for preparing multi-chamber microcapsules. Background Art

[0002] Due to the advantages of its unique structure and preparation method, multi-chamber microcapsules have a wider range of applications in many fields compared to ordinary microcapsules.

[0003] Since 1966, when Iler proposed the self-assembly method of alternately depositing positively and negatively charged substances through electrostatic attraction, this method has developed into an effective method for preparing multi-chamber microcapsules. [R K Iler. J. Colloid Interf. Sci, 1966, 6(21): 569~594.].

[0004] In the early 1990s, Decher et al. used the LbL technology of polymer anion-cation electrostatic interaction to perform layer-by-layer self-assembly of polymers on template microparticles to prepare microcapsules with a solid core-shell structure. The template microparticles in the microcapsules were then dissolved using a solvent to obtain hollow core-shell microcapsules. Through this method, precise control of the microcapsule particle size, shell thickness, and permeability was achieved, providing the possibility for preparing multifunctional microscale delivery systems on solid matrices. [Decher G. Fuzzy nanoassemblies: toward layered polymeric multicomposites [J]. Science, 1997, 277(5330): 1232-1237.].

[0005] Chen et al. used TiO2 precursor Ti(OBu)4 sol as the shell fluid and liquid paraffin as the two-core fluid to prepare double-chamber microcapsules with independently encapsulated liquid paraffin through a composite fluid electrospray method. [H Y Chen, Y Zhao, L Jiang. Chin. Sci. Bull., 2009, 54: 1338~1343.].

[0006] Sun et al. used two active components, blue Wright stain (Wright stain(blue)) and red Rhodamine B (Rhodamine B(red)), as the cores and prepared solid-phase double-chamber microcapsules encapsulating two immiscible active components and separated from each other using the microfluidic double emulsification method, which is expected to be applied in the fields of multifunctional microcapsules and microreactors. [B J Sun, H C Shum, C Holtze et al. ACS Appl. Mater. Interf., 2010, 2(12): 3411~3416.].

[0007] Swiston et al. proposed the application of microcapsule drug delivery systems on living cells. As a drug carrier system, multi-chamber microcapsules will develop in the direction of precisely controlling the release of drugs at specified times and specific sites. [A J Swiston, J B Gilbert, D J Irvine et al. Biomacromolecules, 2010, 11(7): 1826~1832.].

[0008] Kreft et al. embedded gold nanoparticles into the wall of PSS / PAH polyelectrolyte microcapsules to prepare "shell-in-shell" concentric double-chamber microcapsules with photo-responsive properties, with the inner core loaded with TRITC-dextran (dextra) and the outer core loaded with fluorescein isocyanate dextran (FITC). [A J Swiston, J B Gilbert, D J Irvine et al. Biomacromolecules, 2010, 11(7): 1826~1832.].

[0009] Arghya et al. used alginate-chitosan (AC) as the wall material and polyethylene glycol (PEG) as the core material to prepare AC-PEG multi-chamber microcapsules encapsulating baculovirus cells. The encapsulated virus cells can not only survive, but also achieve the expression of transgenes, and are expected to be used for stem cell delivery and gene therapy, especially having unique application prospects in the field of myocardial failure tissue regeneration. [A J Swiston, J B Gilbert, D J Irvine et al. Biomacromolecules, 2010, 11(7): 1826~1832.].

[0010] However, the current preparation methods of multi-chamber microcapsules still have the following problems: 1) The operation of encapsulating multiple active components is cumbersome; 2) The encapsulation efficiency is low; 3) The encapsulated components are inactivated; 4) The sample morphology is relatively uncontrollable. Summary of the Invention

[0011] The technical problem to be solved by the present invention is to provide a preparation method of multi-chamber microcapsules. In the stage of preparing nano-capsules, this preparation method can simply and quickly obtain nano-capsules with regular morphology, uniform particle size distribution, and loaded with multiple drugs; in the stage of preparing multi-chamber microcapsules, the spray drying technology can effectively reduce particle breakage, aggregation, and the generation of solid microspheres. The multi-chamber microcapsules prepared by this preparation method have regular particle morphology, and the size of the microcapsules is 500nm - 10μm.

[0012] To solve the above technical problems, the technical solutions adopted by the present invention are as follows :

[0013] A preparation method of multi-chamber microcapsules, comprising the following steps:

[0014] 1) Mix the aqueous phase containing a surface modifier with the oil phase containing a non-polar solvent and a pesticide, and perform ultrasonic emulsification to obtain an emulsion as the soft template for preparing nano-capsules;

[0015] 2) Add an acid-base regulator and a polymer to the above template solution for reaction to obtain a crude nano-capsule product;

[0016] 3) After washing to remove the residual polymer and surfactant in the crude nano-capsule product, nano-capsules are obtained;

[0017] 4) Disperse the nano-capsules obtained in step 3) in a solvent to obtain a dispersion liquid, and then spray-dry the dispersion liquid to prepare multi-chamber micro-capsules with the nano-capsules as the shell layer.

[0018] Preferably, in step 1), the surface modifier is selected from one of the following substances: sodium dodecyl sulfate, cetyltrimethylammonium bromide, cetylmethylammonium chloride, sodium dodecylbenzenesulfonate, fatty alcohol polyoxyethylene ether sulfate, secondary alkyl sulfonate sodium chloride, alcohol ether carboxylate.

[0019] Preferably, in step 1), the non-polar solvent is selected from one or more of the following substances: hexadecane, dodecane, octadecane.

[0020] Preferably, in step 1), the oil phase of the non-polar solvent is selected from one or more of the following substances: dimethyl sulfoxide, isopropyl alcohol, n-butanol, acetone, acetonitrile, tetrahydrofuran, toluene.

[0021] Preferably, in step 1), the pesticide is selected from one or more of the following substances: abamectin, pyraclostrobin, pinoxaden, prothioconazole, chlorantraniliprole, clothianidin, thiamethoxam, imidacloprid; more preferably, the pesticide is: abamectin, pyraclostrobin.

[0022] Preferably, in step 1), the dosage of the surface modifier is 0.1-1 wt% of the total mass of the aqueous phase; more preferably, the dosage of the surface modifier is 0.2-0.8 wt% of the total mass of the aqueous phase.

[0023] Preferably, in step 1), the dosage of the non-polar solvent is 10-20 wt% of the total mass of the oil phase; more preferably, the dosage of the non-polar solvent is 10-15 wt% of the total mass of the oil phase.

[0024] Preferably, in step 1), the ultrasonic emulsification power is 100-300 W; more preferably, the ultrasonic emulsification power at different levels is 200-250 W; the temperature of the ultrasonic emulsification is 20-80 °C; more preferably, the temperature of the ultrasonic emulsification is 30-40 °C.

[0025] Preferably, in step 2), the mass ratio of the acid-base regulator to the polymer is 1:1 - 1:5; more preferably, the mass ratio of the acid-base regulator to the polymer is 1:1 - 1:2.

[0026] Preferably, in step 2), the reaction time is 12 - 48 h; more preferably, the reaction time is 20 - 28 h.

[0027] Preferably, in step 2), the acid-base regulator is selected from one or more of sodium hydroxide, sodium bicarbonate, and disodium hydrogen phosphate.

[0028] Preferably, in step 2), the polymer is selected from one or more of chitosan, polydopamine, and lignin.

[0029] Preferably, in step 3), the washing method is suction filtration or dialysis.

[0030] Preferably, in step 4), the inlet temperature of the spray drying is 80°C - 180°C; more preferably, the inlet temperature of the spray drying is 100°C - 140°C.

[0031] Preferably, in step 4), the outlet temperature of the spray drying is 40°C - 100°C; more preferably, the outlet temperature of the spray drying is 60°C - 90°C.

[0032] Preferably, in step 4), the feeding rate of the spray drying is 20 - 40 mL / min; more preferably, the feeding rate of the spray drying is 23 - 35 mL / min.

[0033] Preferably, in step 4), the velocity of the compressed gas for the spray drying is 6 - 10 L / min; more preferably, the velocity of the compressed gas for the spray drying is 7 - 9 L / min.

[0034] Any range described in the present invention includes the end values, any value between the end values, and any sub-range formed by any value between the end values or the end values.

[0035] Unless otherwise specified, each raw material in the present invention can be obtained by commercial purchase, and the equipment used in the present invention can be conventional equipment in the field or can be referred to the existing technology in the field.

[0036] Compared with the prior art, the present invention has the following beneficial effects:

[0037] 1) The nano-capsules prepared by the present invention have small particle size and uniform distribution, which are 18 nm - 200 nm, their morphology can be regulated, and the dispersibility of the capsules is relatively good;

[0038] 2) The present invention can flexibly control the size and wall thickness of the nanocapsules by varying the particle size of the template particles, the reaction solution, the reaction time, etc., so as to achieve the performance of loading and sustained release of different drugs;

[0039] 3) The multi-chamber microcapsule particles prepared by the present invention have a stable particle morphology, and ≥99% of the microcapsule particles are regular, with a particle size between 1 μm and 10 μm;

[0040] 4) The preparation method of the multi-chamber microcapsule particles of the present invention has a higher yield, low cost, is simple and fast compared with the traditional preparation method, and is easy to industrialize. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] The following further describes in detail the specific embodiments of the present invention with reference to the drawings

[0042] Figure 1 SEM image of the multi-chamber microcapsules prepared at a feed temperature of 120 °C in Example 1;

[0043] Figure 2 SEM image of the multi-chamber microcapsules prepared at a feed temperature of 140 °C in Example 1;

[0044] Figure 3 SEM image of the multi-chamber microcapsules prepared at a feed temperature of 160 °C in Example 1;

[0045] Figure 4 SEM image of the multi-chamber microcapsules loaded with the pesticide abamectin in Example 2;

[0046] Figure 5 Confocal microscopy image of the multi-chamber microcapsules loaded with the pesticide abamectin and congo red dye in Example 3;

[0047] Figure 6 SEM image of the multi-chamber microcapsules embedded with congo red dye in Example 3;

[0048] Figure 7 SEM image of the multi-chamber microcapsules prepared at a feed rate of 16 mL / min in Comparative Example 1;

[0049] Figure 8 SEM image of the multi-chamber microcapsules prepared at a feed rate of 32 mL / min in Comparative Example 2;

[0050] Figure 9 SEM image of the multi-chamber microcapsules prepared at a compressed gas velocity of 6 L / min in Comparative Example 4. SPECIFIC EMBODIMENTS

[0051] To illustrate the present invention more clearly, the present invention will be further described below in conjunction with preferred embodiments and the accompanying drawings. Similar components in the drawings are denoted by the same reference numerals. Those skilled in the art should understand that the content specifically described below is illustrative rather than restrictive, and should not limit the protection scope of the present invention.

[0052] Various cross-sectional views according to the disclosed embodiments of the present invention are shown in the drawings. These figures are not drawn to scale, where for the purpose of clear illustration, certain details are enlarged and certain details may be omitted. The shapes of various regions and layers shown in the figures, as well as their relative sizes and positional relationships, are merely exemplary, and may deviate in practice due to manufacturing tolerances or technical limitations. And those skilled in the art can design regions / layers with different shapes, sizes, and relative positions according to actual needs.

[0053] As an aspect of the present invention, a method for preparing a multi-chamber microcapsule of the present invention includes the following steps:

[0054] 1) Mix an aqueous phase containing a surface modifier with an oil phase containing a non-polar solvent and a pesticide and ultrasonically emulsify to obtain an emulsion as a soft template for preparing nano-capsules;

[0055] 2) Add an acid-base regulator and a polymer to the above template solution for reaction to obtain a crude nano-capsule;

[0056] 3) Wash and remove the residual polymer and surfactant in the crude nano-capsule to obtain nano-capsules;

[0057] 4) Disperse the nano-capsules obtained in step 3) in a solvent to obtain a dispersion, and then spray-dry the dispersion to prepare a multi-chamber microcapsule with the nano-capsules as the shell layer.

[0058] According to certain embodiments of the present invention, in step 1), the surface modifier is selected from one of the following substances: sodium dodecyl sulfate, cetyltrimethylammonium bromide, cetylmethylammonium chloride, sodium dodecylbenzenesulfonate, fatty alcohol polyether sulfate, secondary alkyl sulfonate sodium chloride, alcohol ether carboxylate; the presence of the surfactant reduces the oil-water interfacial tension, which can make the emulsification process proceed better and form more dispersed emulsion droplets. Selecting other surfactants cannot stabilize the emulsion droplets or improve the dispersion of the emulsion droplets.

[0059] According to certain embodiments of the present invention, in step 1), the non-polar solvent is selected from one or more of the following substances: hexadecane, dodecane, octadecane; selecting other solvents cannot form an obvious hollow structure.

[0060] According to certain embodiments of the present invention, in step 1), the oil phase of the non-polar solvent is selected from one or more of the following substances: dimethyl sulfoxide, isopropyl alcohol, n-butanol, acetone, acetonitrile, tetrahydrofuran, toluene; selecting other oil phases is not suitable for miscibility with the solvent or not suitable for dissolving pesticides.

[0061] According to certain embodiments of the present invention, in step 1), the pesticide is selected from one or more of the following substances: abamectin, pyraclostrobin, pinoxaden, prothioconazole, chlorantraniliprole, clothianidin, thiamethoxam, imidacloprid; more preferably, the different types of pesticides are: abamectin, pyraclostrobin; selecting other pesticides will affect the morphology and dispersibility of the nanocapsules.

[0062] According to certain embodiments of the present invention, in step 1), the dosage of the surface modifier is 0.1-1 wt% of the total mass of the aqueous phase; more preferably, the dosage of the surface modifier is 0.2-0.8 wt% of the total mass of the aqueous phase; outside this dosage range, if it is less, the dispersion degree of the nanocapsules is poor; if it is more, the morphology of the prepared nanocapsules is poor.

[0063] According to certain embodiments of the present invention, in step 1), the dosage of the non-polar solvent is 10-20 wt% of the total mass of the oil phase; more preferably, the dosage of the non-polar solvent is 10-15 wt% of the total mass of the oil phase; outside this dosage range, if it is less, the hollow structure of the nanocapsules is not obvious; if it is more, the size of the prepared nanocapsules is uncontrollable.

[0064] According to certain embodiments of the present invention, in step 1), the ultrasonic emulsification power is 100-300 W; more preferably, the different degrees of ultrasonic emulsification power are 200-250 W; the temperature of the ultrasonic emulsification is 20-80 °C; more preferably, the temperature of the ultrasonic emulsification is 30-40 °C; outside this emulsification power range, the emulsion will be unevenly emulsified or the emulsion droplets will be too small, affecting the pesticide loading; outside this temperature range, the loaded drug will lose its activity.

[0065] According to certain embodiments of the present invention, in step 2), the mass ratio of the acid-base regulator to the polymer is: 1:1-1:5; more preferably, the mass ratio of the acid-base regulator to the polymer is: 1:1-1:2; outside this ratio range, the polymerization ability of the polymer will decrease or it will polymerize too fast and self-polymerize into spheres, unable to form a better hollow state.

[0066] According to certain embodiments of the present invention, in step 2), the reaction time is 12-48 h; more preferably, the reaction time is 20-28 h; outside this time range, the polymer has not reacted completely or the reaction time is too long, which will cause the wall thickness of the obtained nanocapsules to be too low or too high.

[0067] According to certain embodiments of the present invention, in step 3), the washing method is suction filtration or dialysis; other washing methods may cause damage to the structure of the nanocapsules outside the aforementioned washing methods.

[0068] According to certain embodiments of the present invention, in step 4), the inlet temperature of the spray drying is 80°C - 180°C; more preferably, the inlet temperature of the spray drying is 100°C - 140°C; outside this temperature range, if it is too low, large voids will be generated on the wall of the microcapsule, and if it is too high, the microcapsule will be damaged and the morphology will become uncontrollable.

[0069] According to certain embodiments of the present invention, in step 4), the outlet temperature of the spray drying is 40°C - 100°C; more preferably, the outlet temperature of the spray drying is 60°C - 90°C; outside this temperature range, if it is too low, the particle size of the microcapsule will increase and agglomeration will occur, and if it is too high, the microcapsule will be damaged and the morphology will become uncontrollable.

[0070] According to certain embodiments of the present invention, in step 4), the feeding rate of the spray drying is 20 - 40 mL / min; more preferably, the feeding rate of the spray drying is 23 - 35 mL / min; outside this rate range, if it is too low, the particle size of the microcapsule will be small and the particle size difference will be large, and if it is too high, the particle size of the microcapsule will be large and the morphology will become uncontrollable.

[0071] According to certain embodiments of the present invention, in step 4), the speed of the compressed gas for the spray drying is 6 - 10 L / min; more preferably, the speed of the compressed gas for the spray drying is 7 - 9 L / min; outside this rate range, if it is too low, the sphericity of the microcapsule will be low, and if it is too high, the microcapsule will be easily damaged and not formed, and the morphology will be irregular.

[0072] Example 1

[0073] A method for preparing a multi-chamber microcapsule, comprising the following steps:

[0074] Step 1: Preparation of nanocapsules as wall materials

[0075] Dissolve 0.024 g of hexadecane in 0.15 g of toluene as the oil phase; dissolve 0.024 g of sodium dodecylbenzenesulfonate in 10 mL of deionized water as the water phase. After mixing the water phase and the oil phase, use a cell crusher to continuously emulsify the water phase and the oil phase in an ice-water bath for 10 min at a power of 250 W to obtain an emulsion. After diluting the emulsion 20 times with deionized water, add 0.18 g of hydrochloric acid dopamine and 0.115 g of Tris to the diluted solution, and continuously stir for 24 h under magnetic stirring at a rotation speed of 600 rpm. Obtain nanocapsules by suction filtration washing and vacuum drying at 40°C for 12 h;

[0076] Step 2: Preparation of multi-chamber microcapsules by spray drying

[0077] Disperse 0.18 g of nano-capsules in 200 ml of deionized water. Divide 200 mL of the above dispersion into three portions and perform spray drying separately. The inlet temperature of the feed is set at 120 °C, 140 °C, and 160 °C respectively, the feed rate is 24 mL / min, the compressed gas rate is 8 L / min, and then perform spray drying. After the spray drying is completed, take out the microcapsule product in the collection chamber.

[0078] Figure 1 Scanning electron micrograph of multi-chamber microcapsules prepared at a feed temperature of 120 °C, with a particle size of approximately 1.25 μm;

[0079] Figure 2 Scanning electron micrograph of multi-chamber microcapsules prepared at a feed temperature of 140 °C, with a particle size of approximately 1.64 μm;

[0080] Figure 3 Scanning electron micrograph of multi-chamber microcapsules prepared at a feed temperature of 160 °C, with a particle size of approximately 1.88 μm.

[0081] Example 2

[0082] A preparation method of multi-chamber microcapsules loaded with the pesticide abamectin, comprising the following steps:

[0083] Step 1: Preparation of nano-capsules as the wall material

[0084] Dissolve 0.024 g of hexadecane and 0.02 g of abamectin in 0.15 g of toluene as the oil phase; dissolve 0.024 g of sodium dodecylbenzenesulfonate in 10 mL of deionized water as the water phase. After mixing the water phase and the oil phase, use a cell crusher to continuously emulsify the water phase and the oil phase in an ice-water bath at a power of 250 W for 10 min to obtain an emulsion. Dilute the emulsion 20 times with deionized water, then add 0.18 g of hydrochloric acid dopamine and 0.115 g of Tris to the diluted solution, and continuously stir for 24 h under magnetic stirring at a rotation speed of 600 rpm. Obtain the abamectin-loaded nano-capsules by suction filtration, washing, and drying;

[0085] Step 2: Preparation of multi-chamber microcapsules by spray drying

[0086] Disperse 0.18 g of nano-capsules loaded with the pesticide abamectin in 200 ml of deionized water. Take the above mixed liquid loaded with abamectin for spray drying. Set the inlet temperature of the feed at 140 °C, the outlet temperature at 80 °C, the feed rate at 24 mL / min, the compressed gas rate at 8 L / min, and then perform spray drying. After the spray drying is completed, take out the microcapsule product in the collection chamber.

[0087] Figure 4 Scanning electron microscope image of a multi - chamber microcapsule with abamectin pesticide loaded in the nanocapsule, and the particle size is about 1.68 μm.

[0088] Example 3

[0089] A preparation method of a multi - chamber microcapsule loaded with abamectin pesticide and congo red, comprising the following steps:

[0090] Step 1: Preparation of nanocapsules as wall materials

[0091] Dissolve 0.024 g of hexadecane and 0.02 g of abamectin in 0.15 g of toluene as the oil phase; dissolve 0.024 g of sodium dodecylbenzenesulfonate in 10 mL of deionized water as the water phase. After mixing the water phase and the oil phase, use a cell crusher to continuously emulsify the water phase and the oil phase in an ice - water bath for 10 min at a power of 250 W to obtain an emulsion. Dilute the emulsion 20 times with deionized water, then add 0.18 g of hydrochloric acid dopamine and 0.115 g of Tris to the diluted solution, and continuously stir for 24 h under magnetic stirring at a speed of 600 rpm. Obtain the abamectin - loaded nanocapsules by suction filtration, washing, and drying;

[0092] Step 2: Preparation of multi - chamber microcapsules by spray drying

[0093] Dissolve 0.18 g of abamectin - loaded nanocapsules and 0.02 g of congo red in 200 ml of deionized water and dissolve them fully. Take the above - mentioned mixed liquid loaded with abamectin nanocapsules for spray drying, set the inlet temperature to 140 °C, the outlet temperature to 80 °C, the feeding rate to 24 mL / min, and the compressed gas rate to 8 L / min, and then carry out spray drying. After spray drying is completed, take out the microcapsule product in the collection chamber.

[0094] Figure 5 Confocal microscope image of a multi - chamber microcapsule loaded with abamectin pesticide and congo red dye. It can be seen from the figure that the cavity of the microcapsule shows red, indicating that the congo red dye has been successfully embedded into the microcapsule;

[0095] Figure 6 Scanning electron microscope image of a multi - chamber microcapsule embedded with congo red dye. It can be seen from the figure that the microcapsules have a high sphericity and good morphology.

[0096] Example 4

[0097] A preparation method of a multi - chamber microcapsule loaded with abamectin pesticide and urea, comprising the following steps:

[0098] Step 1: Preparation of nanocapsules as wall materials

[0099] 0.024g hexadecane and 0.02g avermectin were dissolved in 0.15g toluene as the oil phase; 0.024g sodium dodecylbenzene sulfonate was dissolved in 10mL deionized water as the water phase. After the water phase and the oil phase were mixed, a cell crusher was used to continuously emulsify the water phase and the oil phase in an ice water bath at a power of 250W for 10min to obtain an emulsion. After the emulsion was diluted 20 times with deionized water, 0.18g dopamine hydrochloride and 0.115g Tris were added to the diluted solution, and the magnetic stirring was continued for 24h at a speed of 600rpm, and the nanocapsules loaded with avermectin were obtained by suction filtration, washing and drying;

[0100] Step 2: Preparation of multi-chamber microcapsules by spray drying

[0101] 0.18g of nanocapsules loaded with pesticide avermectin and 0.2g of urea were dissolved in 200ml of deionized water and fully dissolved. The mixed liquid loaded with avermectin nanocapsules was spray dried, the feed inlet temperature was set to 140°C, the outlet temperature was 80°C, the feed rate was 24mL / min, the compressed gas rate was 8L / min, and then spray dried, and the microcapsule product in the collection chamber was taken out after spray drying.

[0102] Example 5

[0103] A method for preparing a multi-chamber microcapsule comprises the following steps:

[0104] Step 1: Preparation of nanocapsules as capsule wall materials

[0105] 0.024g hexadecane was dissolved in 0.15g toluene as the oil phase; 0.024g sodium dodecylbenzene sulfonate was dissolved in 10mL deionized water as the water phase. After the water phase and the oil phase were mixed, the water phase and the oil phase were continuously emulsified in an ice water bath at 250W power for 10 minutes using a cell crusher to obtain an emulsion. After the emulsion was diluted 20 times with deionized water, 0.18g dopamine hydrochloride and 0.115g Tris were added to the diluted solution, and the solution was continuously stirred for 24 hours under magnetic stirring at a speed of 600rpm, and the nanocapsules were obtained by suction filtration, washing, and vacuum drying at 40°C for 12 hours;

[0106] Step 2: Preparation of multi-chamber microcapsules by spray drying

[0107] Disperse 0.18 g of nano-capsules in 200 ml of deionized water. Divide 200 mL of the above-mentioned dispersion into four portions and conduct spray drying respectively. Set the inlet temperature of the feed to 140 °C, the outlet temperature to 80 °C, the feed rates to 24 mL / min respectively, and the compressed gas rates for spray drying of the four portions of the dispersion to 6 L / min, 7 L / min, 8 L / min, and 9 L / min respectively. Then conduct spray drying respectively, and take out the micro-capsule products in the collection chamber after spray drying is completed.

[0108] Example 6

[0109] A method for preparing multi-chamber micro-capsules, comprising the following steps:

[0110] Step 1: Preparation of nano-capsules as wall materials

[0111] Dissolve 0.024 g of hexadecane in 0.15 g of toluene as the oil phase; dissolve 0.024 g of sodium dodecylbenzenesulfonate in 10 mL of deionized water as the water phase. After mixing the water phase and the oil phase, use a cell crusher to continuously emulsify the water phase and the oil phase in an ice-water bath at a power of 250 W for 10 min to obtain an emulsion. Dilute the emulsion 20 times with deionized water, then add 0.18 g of dopamine hydrochloride and 0.115 g of Tris to the diluted solution, and continuously stir for 24 h under magnetic stirring at a rotation speed of 600 rpm. Obtain nano-capsules through suction filtration, washing, and vacuum drying at 40 °C for 12 h;

[0112] Step 2: Preparation of multi-chamber micro-capsules by spray drying

[0113] Disperse 0.18 g of nano-capsules in 200 ml of deionized water. Divide 200 mL of the above-mentioned dispersion into three portions and conduct spray drying respectively. Set the inlet temperature of the feed to 140 °C, the outlet temperature to 80 °C, the feed rates to 16 mL / min, 24 mL / min, and 32 mL / min respectively, and the compressed gas rate to 8 L / min. Then conduct spray drying respectively, and take out the micro-capsule products in the collection chamber after spray drying is completed.

[0114] Comparative Example 1

[0115] Repeat Example 1: The difference is only that the feed rate is 16 mL / min;

[0116] For the multi-chamber micro-capsules of this comparative example, due to the low feed rate in the spray drying stage, fewer particles enter in the same time, and the particle size distribution of the prepared micro-capsules is non-uniform. The multi-chamber micro-capsules prepared with a feed rate of 16 mL / min are as Figure 7 shown.

[0117] Comparative Example 2

[0118] Repeat Example 1, with the only difference being that the feeding rate is 32 mL / min.

[0119] In this comparative example, due to the high feeding rate during the spray drying stage, more particles entered within the same time, resulting in microcapsules with overly large and non-uniform particle sizes. The multi-chamber microcapsules prepared at a feeding rate of 32 mL / min are as shown in Figure 8 shown.

[0120] Comparative Example 3

[0121] Repeat Example 1, with the only difference being that the inlet temperature is 80 °C.

[0122] When comparing the microcapsule product of this comparative example with that of Example 1, the microcapsule product of this comparative example has good dispersibility. However, under the condition of an inlet temperature of 80 °C, the microcapsule wall particles have low adhesiveness and the product has a low ball formation rate.

[0123] Comparative Example 4

[0124] Repeat Example 1, with the only difference being that the compressed gas speed of the spray dryer is 6 L / min.

[0125] The ball formation rate of the microcapsule product in this comparative example is less than 60%, and the particle sizes of the microcapsules are non-uniform. The scanning electron microscope image of the multi-chamber microcapsules prepared at a compressed gas speed of 6 L / min is as shown in Figure 9 .

[0126] Comparative Example 5

[0127] Repeat Example 1, with the only difference being that the compressed gas speed of the spray dryer is 10 L / min.

[0128] During the preparation of the microcapsules in this comparative example, due to the too low pressure, the efficiency of spraying the feed liquid into droplets is too low, and even a state of flowing down in a stream occurs, making it impossible to carry out the synthesis of microcapsules in the droplet drying stage.

[0129] Comparative Example 6

[0130] Repeat Example 1, with the only difference being that after mixing the aqueous phase and the oil phase, a cell crusher is used for emulsification at a power of 150 W.

[0131] The particle morphology of the multi-chamber microcapsules in this comparative example is severely shrunk and not formed.

[0132] Comparative Example 7

[0133] Repeat Example 1: The only difference is that after mixing the aqueous phase and the oil phase, a cell crusher is used for emulsification at a power of 300 W.

[0134] In this comparative example, the particle sizes of the multi-chamber microcapsule particles are not uniform, and the drug loading amount is too low.

[0135] Comparative Example 8

[0136] Repeat Example 1: The only difference is that after mixing the aqueous phase and the oil phase, a cell crusher is used for emulsification at a power of 250 W for 5 min.

[0137] In this comparative example, the emulsification stage in the preparation of the nanocapsules is incomplete, demulsification occurs, the sphericity of the multi-chamber microcapsule particles is low, and the particle sizes are not uniform.

[0138] Comparative Example 9

[0139] Repeat Example 1: The only difference is that the continuous stirring time in the preparation stage of the nanocapsules is 12 h.

[0140] In this comparative example, the reaction in the preparation stage of the nanocapsules is insufficient, the forming rate of the nanocapsules is low, the morphology of the multi-chamber microcapsules is irregular, and the sphericity is low.

[0141] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, rather than limitations on the implementation manners of the present invention. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is impossible to list all the implementation manners here. Any obvious changes or modifications derived from the technical solutions of the present invention still fall within the protection scope of the present invention.

Claims

1. A method for preparing a multi-chamber microcapsule, characterized in that: The steps include: 1) mixing an aqueous phase containing a surface modifier with an oil phase containing a non-polar solvent and a pesticide and ultrasonically emulsifying the obtained emulsion as a soft template for preparing nanocapsules; 2) adding an acid-base regulator and a polymer to the template solution to react and obtain a preliminary product of nanocapsules; 3) washing to remove the residual polymer and surfactant in the initial nanocapsule product to obtain the nanocapsule; 4) dispersing the nanocapsules obtained in step 3) in a solvent to obtain a dispersion, and then spray-drying the dispersion to prepare multi-chamber microcapsules using the nanocapsules as a shell layer.

2. The method for preparing the multi-chamber microcapsule according to claim 1, characterized in that: In step 1), the surface modifier is selected from one of the following substances: sodium dodecyl sulfate, hexadecyltrimethylammonium bromide, hexadecylmethylammonium chloride, sodium dodecylbenzene sulfonate, sodium sulfate of fatty alcohol ether, sodium chloride of secondary alkyl sulfonate, and alcohol ether carboxylate.

3. The method for preparing the multi-chamber microcapsule according to claim 1, characterized in that: In step 1), the non-polar solvent is selected from one or more of the following substances: hexadecane, dodecane, and octadecane.

4. The method for preparing the multi-chamber microcapsule according to claim 1, characterized in that: In step 1), the oil phase of the non-polar solvent is selected from one or more of the following substances: dimethyl sulfoxide, isopropanol, n-butanol, acetone, acetonitrile, tetrahydrofuran, and toluene.

5. The method for preparing the multi-chamber microcapsule according to claim 1, characterized in that: In step 1), the pesticide is selected from one or more of the following substances: avermectin, pyraclostrobin, pinoxaden, prothioconazole, chlorfenapyr, clothianidin, thiamethoxam, and imidacloprid; more preferably, the pesticide is: avermectin and pyraclostrobin.

6. The method for preparing the multi-chamber microcapsule according to claim 1, characterized in that: In step 1), the amount of the surface modifier is 0.1-1 wt% of the total mass of the aqueous phase; more preferably, the amount of the surface modifier is 0.2-0.8 wt% of the total mass of the aqueous phase.

7. The method for preparing the multi-chamber microcapsule according to claim 1, characterized in that: In step 1), the amount of the non-polar solvent is 10-20 wt% of the total mass of the oil phase; more preferably, the amount of the non-polar solvent is 10-15 wt% of the total mass of the oil phase; Preferably, in step 1), the ultrasonic emulsification power is 100-300W; more preferably, the ultrasonic emulsification power of different degrees is 200-250W; the ultrasonic emulsification temperature is 20-80°C; more preferably, the ultrasonic emulsification temperature is 30-40°C.

8. The method for preparing the multi-chamber microcapsule according to claim 1, characterized in that: In step 2), the mass ratio of the acid-base regulator to the polymer is 1:1-1:5; more preferably, the mass ratio of the acid-base regulator to the polymer is 1:1-1:2; Preferably, in step 2), the reaction time is 12-48 hours; more preferably, the reaction time is 20-28 hours; Preferably, in step 2), the acid-base regulator is selected from one or more of sodium hydroxide, sodium bicarbonate, and disodium hydrogen phosphate; Preferably, in step 2), the polymer is selected from one or more of chitosan, polydopamine and lignin.

9. The method for preparing the multi-chamber microcapsule according to claim 1, characterized in that: Preferably, in step 3), the washing method is suction filtration or dialysis.

10. The method for preparing the multi-chamber microcapsule according to claim 1, characterized in that: In step 4), the inlet temperature of the spray drying is 80°C-180°C; more preferably, the inlet temperature of the spray drying is 100°C-140°C; Preferably, in step 4), the outlet temperature of the spray drying is 40°C-100°C; more preferably, the outlet temperature of the spray drying is 60°C-90°C; Preferably, in step 4), the feed rate of the spray drying is 20-40 mL / min; more preferably, the feed rate of the spray drying is 23-35 mL / min; Preferably, in step 4), the compressed gas rate of the spray drying is 6-10 L / min; more preferably, the compressed gas rate of the spray drying is 7-9 L / min.

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