Method for preparing vaterite based on continuous instantaneous nano precipitation technology

Abstract

The invention provides a method for preparing vaterite based on a continuous instantaneous nano precipitation technology. According to the invention, carboxymethylated xylan (CMX) is used as an organic matrix for calcium carbonate nucleation and a crystal growth inhibitor, the carboxymethylated xylan (CMX) and carbonate are co-precipitated in a multi-channel vortex mixer (MIVM), and stable vaterite (CaCO3 (at) CMX) is generated through an instantaneous nano-precipitation technology; the vaterite has the advantages of narrow particle size distribution range and high specific surface area, the particle size range is 1-1.5 mu m, and the specific surface area reaches 97.28 m < 2 > / g; the vaterite has potential application value in the aspect of active ingredient delivery, can be used as an agricultural chemical loading platform, and has good practicability.

Description

Technical Field

[0001] The invention belongs to the technical field of inorganic porous material preparation, and in particular relates to a method for preparing vaterite based on continuous instantaneous nano precipitation technology. Background Art

[0002] Calcium carbonate (CaCO3) is an important inorganic mineral in biological and geological systems. It has excellent biocompatibility and biodegradability and is widely used in plastics, papermaking, inks, building materials, textiles, cosmetics, and food. Crystalline CaCO3 presents three polymorphs: rhombic calcite, orthorhombic aragonite, and hexagonal vaterite, arranged in order of decreasing thermodynamic stability. Vaterite has high loading capacity and low manufacturing cost, and is a very promising inorganic platform for drug delivery. However, vaterite is extremely unstable and can be easily converted into calcite, so it is necessary to explore a preparation method that can stabilize vaterite.

[0003] When polysaccharides and other polymers contain carboxyl, hydroxyl and amino groups, they can be used as additives to induce the preferential formation of metastable crystalline forms of calcium carbonate, such as aragonite and vaterite. Xylan is the second most abundant polysaccharide, which has biodegradability, potential film-forming properties and good biocompatibility. It is a recognized huge renewable resource of biopolymers that is currently underutilized; carboxymethylation modification can give polysaccharides excellent adhesion, antioxidant, antibacterial, chelating and coordination capabilities, etc. It is a common method to improve the biological activity and water solubility of natural polysaccharides, but few studies have used it as an inhibitor of calcium carbonate crystal growth.

[0004] High supersaturation is a necessary condition for the successful synthesis of vaterite because high supersaturation is conducive to the nucleation process, while low supersaturation promotes crystal growth. Traditional stirring is difficult to provide extremely high supersaturation in a short period of time, and new technical means such as transient nanoprecipitation technology (FNP) are needed to enhance mixing. FNP technology is a cost-effective, high-throughput, controllable and reproducible technology that can achieve high Reynolds numbers and high supersaturation levels in a multi-inlet vortex mixer (MIVM), promoting the nucleation of calcium carbonate within milliseconds and producing a metastable phase. The vortex environment in the MIVM further ensures uniform conditions that are conducive to the controlled growth of hydrovaterite, resulting in a narrower particle size distribution range for the product. Currently, there are few methods for preparing vaterite using FNP technology. Summary of the invention

[0005] In view of some deficiencies in the prior art, the present invention provides a method for preparing vaterite based on continuous instantaneous nanoprecipitation technology. The present invention uses carboxymethylated xylan (CMX) as an organic matrix and crystal growth inhibitor for calcium carbonate nucleation, and co-precipitates it with carbonate in a multi-channel vortex mixer (MIVM) to generate stable vaterite (CaCO3@CMX) by instantaneous nanoprecipitation technology. The vaterite has the advantages of narrow particle size distribution range and high specific surface area. The particle size range is 1-1.5 μm, and the specific surface area reaches 97.28 m 2 / g; the vaterite has potential application value in the delivery of active ingredients, and can be used as a drug delivery platform for agricultural chemicals with good practicality.

[0006] In order to achieve the above technical objectives, the present invention adopts the following technical means: The present invention first provides a method for preparing vaterite based on continuous instantaneous nanoprecipitation technology, the method comprising: Two parts of CMX aqueous solution and two parts of Ca 2+ Staggered into MIVM to obtain CMX-Ca 2+ Solution; Two parts of CMX-Ca 2+ and two parts CO3 2- The solution is passed into MIVM in a staggered manner to obtain a CaCO3 polymorph solution, which is continuously stirred and subjected to Ostwald ripening after the stirring is completed. After the ripening is completed, the solution is centrifuged, washed, and dried to obtain the vaterite.

[0007] Preferably, the structural formula of the CMX is: , wherein R is H or CH2COONa.

[0008] Preferably, the concentration of the CMX aqueous solution is 0.1-5 mg / mL; 2+ The concentration is 10~100mM.

[0009] Preferably, the CMX aqueous solution and Ca 2+ The inlet flow rates were 10 mL / min~75 mL / min.

[0010] Preferably, the CMX aqueous solution and Ca 2+ The dosage ratio is 10:1~1:10.

[0011] Preferably, CMX-Ca 2+ and CO3 2- The molar ratio of CMX-Ca is 1:1. 2+ and CO3 2-The concentrations were all between 10 and 100 mM.

[0012] Preferably, the conditions for continuing the stirring reaction are: stirring at 100-1000 rpm for 8-24 hours.

[0013] Preferably, the Ostwald ripening conditions are: ripening at 25° C. for 6 to 24 hours.

[0014] The present invention also provides vaterite prepared by the above method, wherein the vaterite is an inorganic hybrid porous spherical material with a particle size of 1 to 1.5 μm.

[0015] The present invention also provides the use of the vaterite as a drug-carrying platform for agricultural chemicals.

[0016] Compared with the prior art, the present invention has the following beneficial effects: (1) The preparation method of vaterite of the present invention is simple, the reaction conditions are mild, the raw materials are pure natural and abundant, and the price is low; the flux is large, and the preparation process is continuous; no organic solvent is used in the preparation process, and it is environmentally friendly and pollution-free.

[0017] (2) The crystal inhibitor CMX used in the preparation process of vaterite in the present invention is a natural renewable resource with good biodegradability and biocompatibility. Its structure is rich in carboxyl and hydroxyl groups and can react with Ca 2+ Complexation forms nucleation sites, thereby reducing the critical nucleation radius and energy barrier, and can provide functional groups that are easy to interact strongly with the wax layer on the leaf surface of crops for the design of agricultural chemical delivery platforms.

[0018] (3) The FNP technology of the present invention can provide a high Reynolds number within milliseconds, providing a high supersaturation required for CaCO3 nucleation to be superior to growth from a kinetic point of view; the vortex pattern formed in the microreactor MIVM provides a uniform reaction space that is conducive to the formation of vaterite, ensuring uniform mixing of materials during the entire reaction process. The vaterite prepared using the FNP technology has a particle size of about 1.11 μm, a narrow particle size distribution range, and a high specific surface area of ​​97.28 m 2 / g.

[0019] (4) The vaterite described in the present invention has good pH responsiveness, biodegradability and biocompatibility, and has broad development potential in the construction of sustainable biopharmaceutical delivery platforms. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 Schematic diagram of the preparation process of CaCO3@CMX.

[0021] Figure 2 CMX-Ca 2+ Particle size distribution of the complex.

[0022] Figure 3 This is the scanning electron microscope image of CaCO3@CMX.

[0023] Figure 4 is the particle size of CaCO3@CMX.

[0024] Figure 5 is the N2 adsorption-desorption curve.

[0025] Figure 6 This is a scanning electron microscope image of CaCO3 prepared in Comparative Example 1. DETAILED DESCRIPTION

[0026] The present invention is further described below in conjunction with the accompanying drawings and specific embodiments, but the protection scope of the present invention is not limited thereto.

[0027] Embodiment 1: (1) 500 mg of carboxymethyl xylan (CMX) was dissolved in 100 mL of deionized water, stirred at 80 °C and 300 rpm for 30 min, allowed to cool to room temperature, and then divided into two equal portions to obtain solutions A1 and A2. 1.76 g of calcium acetate monohydrate was dissolved in 100 mL of deionized water and divided into two equal portions to obtain solutions B1 and B2. A1, B1, A2, and B2 were respectively loaded into 50 mL microinjectors, and four microinjectors were connected to the four inlets of MIVM in the order of A1, B1, A2, and B2. The mixture was mixed under the drive of a peristaltic pump to obtain CMX-Ca 2+ , divided into two equal portions, recorded as solutions C1 and C2.

[0028] (2) Dissolve 1.06 g of sodium carbonate in 100 mL of deionized water and divide into two equal parts to obtain solutions D1 and D2. Load C1, D1, C2, and D2 into 50 mL micro-injectors respectively. Connect the four micro-injectors to the four inlets of MIVM in the order of C1, D1, C2, and D2 to control the CMX-Ca 2+ and CO3 2- The molar ratio of the two compounds was 1:1, and the mixture was mixed under the drive of a peristaltic pump to obtain a polymorph solution. The calcium carbonate polymorph solution was then stirred at 500 rpm for 16 h, aged at room temperature for 12 h, centrifuged, washed and freeze-dried at -18 °C to obtain a milky white powder, vaterite CaCO3@CMX.

[0029] Figure 1 The schematic diagram of the preparation process of CaCO3@CMX shows that CaCO3@CMX is prepared by a two-step FNP method. The first step is CMX-Ca 2+ The second step of the complex preparation process is to use CMX-Ca2+ The complex is a nucleation site, and CO3 2- Combined to form CaCO3@CMX.

[0030] Figure 2 CMX-Ca 2+ The particle size distribution of the complex shows that CMX-Ca 2+ The average diameter of the complex is 50 nm.

[0031] Figure 3 This is a scanning electron microscope image of CaCO3@CMX. It can be seen from the image that CaCO3@CMX is a spherical micron particle with a rough surface and uniform particle size distribution.

[0032] Figure 4 is the particle size of CaCO3@CMX. It can be seen from the figure that the average particle size of CaCO3@CMX is 1.25±0.25 μm.

[0033] Figure 5 It is the N2 adsorption-desorption curve. It can be seen from the figure that the curve presents a type IV curve and an H2 hysteresis loop, which proves that the microspheres are in the form of particle accumulation.

[0034] Embodiment 2: (1) Dissolve 10 mg of carboxymethyl xylan (CMX) in 100 mL of deionized water, stir at 20 °C and 500 rpm for 30 min, let it cool to room temperature, and divide it into two equal parts to obtain solutions A1 and A2; dissolve 0.176 g of calcium acetate monohydrate in 100 mL of deionized water and divide it into two equal parts to obtain solutions B1 and B2; load A1, B1, A2, and B2 into 50 mL microinjectors respectively, and connect the four microinjectors to the four inlets of MIVM in the order of A1, B1, A2, and B2. Set the flow rates of A1 and A2 to 10 mL / min, and the flow rates of B1 and B2 to 10 mL / min. Mix them under the drive of a peristaltic pump to obtain CMX-Ca 2+ , divided into two equal portions, recorded as solutions C1 and C2.

[0035] (2) Dissolve 0.106 g of sodium carbonate in 100 mL of deionized water and divide it into two equal parts to obtain solutions D1 and D2. Load C1, D1, C2, and D2 into 50 mL micro-injectors respectively. Connect the four micro-injectors to the four inlets of MIVM in the order of C1, D1, C2, and D2 to control the CMX-Ca 2+ and CO3 2-The molar ratio of the two substances was 1:1, and the mixture was mixed under the drive of a peristaltic pump to obtain a polymorph solution; the calcium carbonate polymorph solution was then stirred at 1000 rpm for 8 h, aged at room temperature for 8 h after the stirring, centrifuged, washed and freeze-dried at -18°C to obtain a milky white powder, vaterite CaCO3@CMX.

[0036] Embodiment 3: (1) 300 mg of carboxymethyl xylan (CMX) was dissolved in 100 mL of deionized water, stirred at 80 °C and 300 rpm for 30 min, allowed to cool to room temperature, and then divided into two equal portions to obtain solutions A1 and A2. 0.96 g of calcium acetate monohydrate was dissolved in 100 mL of deionized water and divided into two equal portions to obtain solutions B1 and B2. A1, B1, A2, and B2 were respectively loaded into 50 mL microinjectors. Four microinjectors were connected to the four inlets of MIVM in the order of A1, B1, A2, and B2. Mixed under the drive of a peristaltic pump, the flow rates of A1 and A2 were set to 10 mL / min, and the flow rates of B1 and B2 were set to 10 mL / min. CMX-Ca 2+ , divided into two equal portions, recorded as solutions C1 and C2.

[0037] (2) Dissolve 0.53 g of sodium carbonate in 100 mL of deionized water and divide into two equal parts to obtain solutions D1 and D2. Load C1, D1, C2, and D2 into 50 mL micro-injectors respectively. Connect the four micro-injectors to the four inlets of MIVM in the order of C1, D1, C2, and D2, so that CMX-Ca 2+ and CO3 2- The molar ratio of the two compounds was 1:1, and the mixture was mixed under the drive of a peristaltic pump to obtain a polymorph solution. The calcium carbonate polymorph solution was then stirred at 100 rpm for 24 h, aged at room temperature for 24 h, centrifuged, washed and freeze-dried at -18°C to obtain a milky white powder, vaterite CaCO3@CMX.

[0038] Comparative Example 1: In this comparative example, CaCO3 was prepared by a stirring method in the absence of CMX. The preparation method of CaCO3 is as follows: 1.76 g of calcium acetate monohydrate was dissolved in 100 mL of deionized water, and the mixture was stirred with the CMX solution, which was recorded as solution E; 1.06 g of sodium carbonate was dissolved in 100 mL of deionized water, which was recorded as solution F; E and F were mixed at the same time under stirring conditions of 1000 rpm, magnetically stirred for 12 h, centrifuged, washed and freeze-dried at -18°C to obtain the CaCO3.

[0039] Figure 6The scanning electron microscope image of CaCO3 obtained in the comparative example shows that the obtained product is rhombohedral calcite, which shows that the presence of CMX has a significant effect on the growth of calcium carbonate crystals: the CMX in the solution in Example 1 provides nucleation sites that can bind to calcium ions, so that calcium carbonate crystals grow in a controlled manner at the nucleation sites; at the same time, the high supersaturation provided by FNP also makes the nucleation of calcium carbonate better than the growth; the dual control of kinetics and thermodynamics reduces the Gibbs free energy, so that the calcium carbonate crystals are stable in the vaterite state. When there is no crystal inhibitor, the calcium carbonate crystals undergo nucleation, growth and Ostwald ripening to generate the most thermodynamically stable calcite.

[0040] In summary, the present invention uses carboxymethylated xylan (CMX) as an organic matrix and crystal growth inhibitor for calcium carbonate nucleation, co-precipitates it with carbonate in MIVM, and generates stable vaterite by instantaneous nanoprecipitation technology; the vaterite has the advantages of narrow particle size distribution range and high specific surface area, with a particle size range of 1-1.5 μm and a specific surface area of ​​97.28 m 2 / g; the vaterite has potential application value in the delivery of active ingredients, and can be used as a drug delivery platform for agricultural chemicals with good practicality.

[0041] The embodiments are preferred implementations of the present invention, but the present invention is not limited to the above-mentioned implementations. Any obvious improvements, substitutions or modifications that can be made by those skilled in the art without departing from the essential content of the present invention belong to the protection scope of the present invention.

Claims

1. A method for preparing vaterite based on continuous instantaneous nanoprecipitation technology, characterized in that: The method comprises: Two parts of CMX aqueous solution and two parts of Ca 2+ Staggered into MIVM to obtain CMX-Ca 2+ Solution; Two parts of CMX-Ca 2+ and two parts CO3 2- The solution is passed into MIVM in a staggered manner to obtain a CaCO3 polymorph solution, which is continuously stirred and subjected to Ostwald ripening after the stirring is completed. After the ripening is completed, the solution is centrifuged, washed, and dried to obtain the vaterite.

2. The method for preparing vaterite based on continuous instantaneous nanoprecipitation technology according to claim 1, characterized in that: The structural formula of the CMX is: , wherein R is H or CH2COONa.

3. The method for preparing vaterite based on continuous instantaneous nanoprecipitation technology according to claim 1, characterized in that: The concentration of the CMX aqueous solution is 0.1-5 mg / mL; the Ca 2+ The concentration is 10~100mM.

4. The method for preparing vaterite based on continuous instantaneous nanoprecipitation technology according to claim 1, characterized in that: The CMX aqueous solution and Ca 2+ The inlet flow rates were 10 mL / min~75 mL / min.

5. The method for preparing vaterite based on continuous instantaneous nanoprecipitation technology according to claim 1, characterized in that: The CMX aqueous solution and Ca 2+ The dosage ratio is 10:1~1:

10.

6. The method for preparing vaterite based on continuous instantaneous nanoprecipitation technology according to claim 1, characterized in that: CMX-Ca 2+ and CO3 2- The molar ratio of CMX-Ca is 1:

1. 2+ and CO3 2- The concentrations were all between 10 and 100 mM.

7. The method for preparing vaterite based on continuous instantaneous nanoprecipitation technology according to claim 1, characterized in that: The conditions for continuing the stirring reaction are: stirring at 100-1000 rpm for 8-24 hours.

8. The method for preparing vaterite based on continuous instantaneous nanoprecipitation technology according to claim 1, characterized in that: The Ostwald ripening conditions are: ripening at 25° C. for 6 to 24 hours.

9. The vaterite prepared by the method according to any one of claims 1 to 8, characterized in that The vaterite is an inorganic hybrid porous spherical material with a particle size of 1-1.5 μm.

10. Use of the vaterite according to claim 9 as a drug delivery platform for agricultural chemicals.

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