Polysaccharide-based nano-microcapsule and preparation method thereof

Abstract

The invention relates to the technical field of preparation of polysaccharide-based nano microcapsules, in particular to a polysaccharide-based nano microcapsule and a preparation method thereof. The method comprises the following steps: respectively conveying a polysaccharide polymer aqueous solution and a target load oil phase solution through a peristaltic pump, and premixing to obtain a water-oil mixed system; the obtained water-oil mixed system is pushed through a peristaltic pump and enters a continuous flowing ultrasonic environment for ultrasonic treatment, the ultrasonic power is 100-1000 W, and the ultrasonic time is 5-60 min; collecting a product at a discharge port of the equipment after ultrasonic treatment to obtain a polysaccharide-based nano-microcapsule dispersion liquid; and performing drying treatment to obtain the polysaccharide-based nano-microcapsule. The method has the advantages that the process is simple, the production efficiency is high, the cost is low, continuous production in a closed environment can be realized, the production efficiency is effectively improved, the product pollution risk is reduced, and the prepared polysaccharide-based nano-microcapsule is uniform in particle size distribution and high in encapsulation efficiency.

Description

Technical Field

[0001] This invention relates to the field of polysaccharide-based nanocapsule preparation technology, and in particular to a polysaccharide-based nanocapsule and its preparation method. Background Technology

[0002] Microencapsulation encapsulates active ingredients (solid / liquid) within a polymer shell, forming irregular spherical particles. This aims to prolong the storage of active substances and control their release. Physical methods for preparing microcapsules have been widely used since the 1950s when researchers first began researching them. From initial basic physical encapsulation processes such as extrusion and spray drying, modern advanced technologies such as electrospray deposition, sonochemistry, and microfluidics are at the forefront.

[0003] Natural polysaccharides, due to their excellent macromolecular structure, biocompatibility, modifiability, and diversity, have become the raw materials for the synthesis of many microcapsules. The numerous groups on the polysaccharide backbone can directly participate in dynamic covalent / non-covalent reactions, providing a rich selection of functional modifications. Among them, the Chinese invention patent application CN105326810A, published on February 17, 2016, entitled "A Folic Acid-Modified Reduction-Responsive Chitosan Microcapsules and Preparation Method Thereof," and the article "Multi-stimuli responsive smart chitosan-based microcapsules for targeted drug delivery and triggered drug release," report a sonochemical method using folic acid-functionalized thiolated chitosan as a raw material. By inserting an ultrasonic probe into the water-oil interface, ultrasound is used to promote bonding, resulting in polysaccharide-based nanocapsules. However, this method involves direct contact between the ultrasonic probe and the sample during preparation, making it susceptible to contamination and compromising the safety of the sample production process. Furthermore, the reported sonochemical method produces very small yields per batch and has poor size uniformity, which seriously affects the production efficiency of nanocapsules for practical application and greatly limits their application in food, cosmetics, and biomedicine.

[0004] In conclusion, it is necessary to find a low-cost physical preparation method that can effectively improve the safety of the preparation process of polysaccharide-based nanocapsules and increase their production efficiency. Summary of the Invention

[0005] To address the aforementioned problems, this invention provides a polysaccharide-based nanocapsule and its preparation method.

[0006] The primary objective of this invention is to provide a method for preparing polysaccharide-based nanocapsules, specifically comprising the following steps: S1. The polysaccharide polymer aqueous solution and the target loading oil phase solution are respectively delivered and premixed using a peristaltic pump to obtain a water-oil mixture system; S2. The water-oil mixture obtained in step S1 is pushed into a continuous flow ultrasonic environment by a peristaltic pump for ultrasonic treatment. The ultrasonic power is 100~1000W and the ultrasonic time is 5~60min. S3. Collect the product from the equipment outlet after ultrasonic treatment in step S2 to obtain a polysaccharide-based nano-microcapsule dispersion; perform drying treatment to obtain polysaccharide-based nano-microcapsules.

[0007] Preferably, the polysaccharide polymer aqueous solution is a polysaccharide polymer aqueous solution or a thiol polysaccharide polymer aqueous solution, wherein the mass fraction of the polysaccharide polymer is 0.01~5%.

[0008] Preferably, the target loading oil phase solution has a concentration of 0.1~10 mg / ml.

[0009] Preferably, the target loading material is a fat-soluble active substance such as curcumin, quercetin, resveratrol, epigallocatechin gallate, or lutein; the oil phase solution of the target loading material is an ethyl acetate solution of the fat-soluble active substances curcumin, quercetin, resveratrol, epigallocatechin gallate, or lutein.

[0010] Preferably, the speed ratio of the two peristaltic pumps for conveying the polysaccharide polymer aqueous solution and the target loading oil phase solution is 1:10 to 10:1.

[0011] Preferably, the speed ratio of the two peristaltic pumps for conveying the polysaccharide polymer aqueous solution and the target loading oil phase solution is 5:1 to 10:1.

[0012] Preferably, the ultrasonic power in step S2 is 400~1000W and the ultrasonic time is 10~30min.

[0013] Preferably, the drying process in step S3 is spray drying or freeze drying; the particle size of the polysaccharide-based nanocapsules is 100~5000nm.

[0014] The second objective of this invention is to provide a polysaccharide-based nanocapsule, prepared using the aforementioned method for preparing a polysaccharide-based nanocapsule; the particle size of the polysaccharide-based nanocapsule is 100~5000 nm.

[0015] Compared with the prior art, the present invention can achieve the following beneficial effects: This invention provides a continuous flow sonochemical method for preparing polysaccharide-based nanocapsules. Addressing the shortcomings of existing technologies, such as uneven particle size distribution, expensive equipment, and low production efficiency in traditional sonochemical methods, this invention offers a green and efficient method for preparing polysaccharide-based water / oil nanocapsules. The preparation method of this invention can produce polysaccharide-based nanocapsules with a simple process, high production efficiency, and low cost. The duration of online continuous flow ultrasonic treatment or the discharge of the water-oil mixture can be controlled by valve switching, enabling continuous production and effectively improving production efficiency. The resulting polysaccharide-based nanocapsules have a uniform particle size distribution and high encapsulation efficiency. The unencapsulated portion of the target loading oil phase solution can also be recycled for the next cycle, avoiding raw material waste and facilitating subsequent production. Attached Figure Description

[0016] Figure 1 This describes the particle size distribution of polysaccharide-based nanocapsules provided in Examples 1-9 of the present invention.

[0017] Figure 2 These are optical microscope images of polysaccharide-based nanocapsules provided according to embodiments of the present invention; in the figures, AF represent polysaccharide-based nanocapsules prepared in Examples 1, 2, 3, 4, 7 and 8, respectively.

[0018] Figure 3 These are scanning electron microscope images of polysaccharide-based nanocapsules provided according to embodiments of the present invention; in the figures, A, B, and C represent polysaccharide-based nanocapsules prepared in Examples 5, 6, and 9, respectively. Detailed Implementation

[0019] In the following description, embodiments of the invention will be described with reference to the accompanying drawings. In the description below, the same modules are denoted by the same reference numerals. Where the same reference numerals are used, their names and functions are also the same. Therefore, their detailed description will not be repeated.

[0020] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and specific embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and do not constitute a limitation thereof.

[0021] This invention provides a method for preparing polysaccharide-based nanocapsules, aiming to utilize a high-power CNC ultrasonic device with adjustable power and a peristaltic pump to provide a continuous flow ultrasonic environment, thereby preparing polysaccharide-based nanocapsules under continuous flow sonochemical conditions; specifically, it includes the following steps: S1. Premixing: The aqueous solution of polysaccharide polymer and the oil phase solution of the target loading are respectively transported and premixed by peristaltic pumps to obtain an oil-water mixture system; the mixing ratio of the aqueous solution of polysaccharide polymer and the oil phase solution of the target loading is controlled by adjusting the speed ratio of the two peristaltic pumps. Specifically, the polysaccharide polymer aqueous solution is either a polysaccharide polymer aqueous solution or a thiol polysaccharide polymer aqueous solution, and the mass fraction of the polysaccharide polymer is 0.01~5%; Specifically, the target loading material is a fat-soluble active substance such as curcumin, quercetin, resveratrol, epigallocatechin gallate, or lutein; the oil phase solution of the target loading material is an ethyl acetate solution of the fat-soluble active substances curcumin, quercetin, resveratrol, epigallocatechin gallate, or lutein, with a concentration of 0.1~10 mg / ml. Specifically, the speed ratio of the two peristaltic pumps conveying the polysaccharide polymer aqueous solution and the target loading oil phase solution is 1:10 to 10:1; preferably, the speed ratio of the two peristaltic pumps conveying the polysaccharide polymer aqueous solution and the target loading oil phase solution is 5:1 to 10:1. In some embodiments, the polysaccharide polymer aqueous solution is a chitosan solution, sodium alginate solution, carboxymethyl cellulose solution, or starch solution; the thiol polysaccharide polymer aqueous solution is a thiol chitosan solution, thiol sodium alginate solution, thiol carboxymethyl cellulose solution, or thiol starch solution; the target loading oil phase solution is an ethyl acetate solution of 10 mg / ml curcumin, quercetin, resveratrol, epigallocatechin gallate, or lutein.

[0022] S2. Continuous flow ultrasonic treatment: The water-oil mixture obtained in step S1 is pushed into a continuous flow ultrasonic environment by a peristaltic pump for ultrasonic treatment. The ultrasonic power is 100~1000W and the ultrasonic time is 5~60min. Preferably, the ultrasonic power is 400~1000W and the ultrasonic time is 10~30min.

[0023] S3. Product collection: Collect the product from the equipment outlet after ultrasonic treatment in step S2 to obtain a polysaccharide-based nano-microcapsule dispersion; then dry it to obtain a polysaccharide-based nano-microcapsule solid powder. Specifically, the drying methods are spray drying or freeze drying; Specifically, the particle size of the polysaccharide-based nanocapsules is 100~5000nm.

[0024] Example 1 This embodiment provides a method for preparing polysaccharide-based nanocapsules, specifically including the following steps: S1. Premixing: Mix 0.125wt% chitosan solution and 10mg / ml curcumin ethyl acetate solution using a peristaltic pump at a speed ratio of 10:1; S2. Continuous flow ultrasonic treatment: The premixed water-oil mixture is driven by a peristaltic pump into the continuous flow ultrasonic environment of a high-power CNC ultrasonic device for continuous ultrasonic treatment. The ultrasonic power is adjusted to 1000W and the online ultrasonic duration is 30min. S3. Product Collection: The product outlet was collected to obtain a chitosan-based nano-microcapsule dispersion with a particle size of 1503.7 nm; after drying, polysaccharide-based nano-microcapsule solid powder was obtained. The encapsulation efficiency of the polysaccharide-based nano-microcapsules was determined to be 94.67%.

[0025] Example 2 This embodiment provides a method for preparing polysaccharide-based nanocapsules, specifically including the following steps: S1. Premixing: Mix 0.25wt% sodium alginate solution and 10mg / ml curcumin ethyl acetate solution using a peristaltic pump at a speed ratio of 5:1; S2. Continuous flow ultrasonic treatment: The premixed water-oil mixture is driven by a peristaltic pump into the continuous flow ultrasonic environment of a high-power CNC ultrasonic device for continuous ultrasonic treatment. The ultrasonic power is adjusted to 1000W and the online ultrasonic duration is 30min. S3. Product Collection: The product outlet was collected to obtain a sodium alginate-based nano-capsule dispersion with a particle size of 3077.4 nm; after drying, polysaccharide-based nano-capsule solid powder was obtained. The encapsulation efficiency of the polysaccharide-based nano-capsules was determined to be 91.65%.

[0026] Example 3 This embodiment provides a method for preparing polysaccharide-based nanocapsules, specifically including the following steps: S1. Premixing: Mix 0.125wt% carboxymethyl cellulose solution and 10mg / ml curcumin ethyl acetate solution using a peristaltic pump at a speed ratio of 10:1; S2. Continuous flow ultrasonic treatment: The premixed water-oil mixture is driven by a peristaltic pump into the continuous flow ultrasonic environment of a high-power CNC ultrasonic device for continuous ultrasonic treatment. The ultrasonic power is adjusted to 800W and the online ultrasonic duration is 30min. S3. Product Collection: The product outlet was collected to obtain a dispersion of carboxymethyl cellulose-based nanocapsules with a particle size of 2231.7 nm; after drying, polysaccharide-based nanocapsule solid powder was obtained. The encapsulation efficiency of the polysaccharide-based nanocapsules was determined to be 92.65%.

[0027] Example 4 This embodiment provides a method for preparing polysaccharide-based nanocapsules, specifically including the following steps: S1. Premixing: Mix 0.125wt% starch solution and 10mg / ml curcumin ethyl acetate solution using a peristaltic pump at a speed ratio of 10:1; S2. Continuous flow ultrasonic treatment: The premixed water-oil mixture is driven by a peristaltic pump into the continuous flow ultrasonic environment of a high-power CNC ultrasonic device for continuous ultrasonic treatment. The ultrasonic power is adjusted to 1000W and the online ultrasonic duration is 20min. S3. Product Collection: The product outlet was collected to obtain a starch-based nano-microcapsule dispersion with a particle size of 2491.5 nm; after drying, polysaccharide-based nano-microcapsule solid powder was obtained. The encapsulation efficiency of the polysaccharide-based nano-microcapsules was determined to be 91.3%.

[0028] Example 5 This embodiment provides a method for preparing polysaccharide-based nanocapsules, specifically including the following steps: S1. Premixing: Mix 0.125wt% thiolated chitosan solution and 10mg / ml curcumin ethyl acetate solution using a peristaltic pump at a speed ratio of 10:1; S2. Continuous flow ultrasonic treatment: The premixed water-oil mixture is driven by a peristaltic pump into the continuous flow ultrasonic environment of a high-power CNC ultrasonic device for continuous ultrasonic treatment. The ultrasonic power is adjusted to 1000W and the online ultrasonic duration is 10min. S3. Product Collection: The product outlet was collected to obtain a dispersion of thiolized chitosan-based nanocapsules with a particle size of 652.2 nm; after drying, polysaccharide-based nanocapsule solid powder was obtained. The encapsulation efficiency of the polysaccharide-based nanocapsules was determined to be 90.43%.

[0029] Example 6 This embodiment provides a method for preparing polysaccharide-based nanocapsules, specifically including the following steps: S1. Premixing: Mix 0.125wt% sodium alginate solution with 10mg / ml curcumin ethyl acetate solution using a peristaltic pump at a speed ratio of 10:1; S2. Continuous flow ultrasonic treatment: The premixed water-oil mixture is driven by a peristaltic pump into the continuous flow ultrasonic environment of a high-power CNC ultrasonic device for continuous ultrasonic treatment. The ultrasonic power is adjusted to 800W and the online ultrasonic duration is 30min. S3. Product Collection: The product outlet was collected to obtain a dispersion of thiolized sodium alginate-based nanocapsules with a particle size of 425.4 nm; after drying, polysaccharide-based nanocapsule solid powder was obtained. The encapsulation efficiency of the polysaccharide-based nanocapsules was determined to be 94.99%.

[0030] Example 7 This embodiment provides a method for preparing polysaccharide-based nanocapsules, specifically including the following steps: S1. Premixing: Mix 2wt% mercapto-starch solution and 10mg / ml curcumin ethyl acetate solution using a peristaltic pump at a speed ratio of 5:1; S2. Continuous flow ultrasonic treatment: The premixed water-oil mixture is driven by a peristaltic pump into the continuous flow ultrasonic environment of a high-power CNC ultrasonic device for continuous ultrasonic treatment. The ultrasonic power is adjusted to 1000W and the online ultrasonic duration is 30min. S3. Product Collection: The product outlet was collected to obtain a dispersion of thiolized starch-based nanocapsules with a particle size of 2091.2 nm; after drying, polysaccharide-based nanocapsule solid powder was obtained. The encapsulation efficiency of the polysaccharide-based nanocapsules was determined to be 90.47%.

[0031] Example 8 This embodiment provides a method for preparing polysaccharide-based nanocapsules, specifically including the following steps: S1. Premixing: Mix 0.125wt% mercapto-carboxymethyl cellulose solution and 10mg / ml curcumin ethyl acetate solution using a peristaltic pump at a speed ratio of 10:1; S2. Continuous flow ultrasonic treatment: The premixed water-oil mixture is driven by a peristaltic pump into the continuous flow ultrasonic environment of a high-power CNC ultrasonic device for continuous ultrasonic treatment. The ultrasonic power is adjusted to 400W and the online ultrasonic duration is 30min. S3. Product Collection: The product outlet was collected to obtain a dispersion of thiolated carboxymethyl cellulose-based nanocapsules with a particle size of 896.4 nm; after drying, polysaccharide-based nanocapsule solid powder was obtained. The encapsulation efficiency of the polysaccharide-based nanocapsules was determined to be 91.85%.

[0032] Example 9 This embodiment provides a method for preparing polysaccharide-based nanocapsules, specifically including the following steps: S1. Premixing: Mix 0.125wt% thiolated chitosan solution and 10mg / ml epigallocatechin gallate ethyl acetate solution using a peristaltic pump at a speed ratio of 10:1; S2. Continuous flow ultrasonic treatment: The premixed water-oil mixture is driven by a peristaltic pump into the continuous flow ultrasonic environment of a high-power CNC ultrasonic device for continuous ultrasonic treatment. The ultrasonic power is adjusted to 1000W and the online ultrasonic duration is 30min. S3. Product Collection: The product outlet was collected to obtain a dispersion of thiol-chitosan-based nanocapsules with a particle size of 562.8 nm; after drying, polysaccharide-based nanocapsule solid powder was obtained. The encapsulation efficiency of the polysaccharide-based nanocapsules was determined to be 92.26%.

[0033] Figure 1 The figures show the particle size distribution of the polysaccharide-based nanocapsules prepared in Examples 1-9. As can be seen, the particle size distribution of each sample is relatively concentrated, without significant polydispersion. The peak positions of the nanocapsules prepared in different examples are slightly different, indicating that the particle size can be controlled by adjusting process parameters (such as ultrasonic conditions and material ratios).

[0034] The obtained nanocapsules were characterized using an optical microscope. Figure 2 Optical microscope images of the polysaccharide-based nanocapsules prepared in Examples 1, 2, 3, 4, 7, and 8 are shown. Because the nanocapsules obtained in Examples 5, 6, and 9 have relatively small particle sizes, the microscopic imaging results are not ideal; nanocapsules smaller than a certain particle size appear as only black dots when photographed using an optical microscope. Therefore, the nanocapsules obtained in Examples 5, 6, and 9 were characterized using scanning electron microscopy (SEM). Furthermore, the SEM images are of dry samples, and the particle size is significantly smaller than that obtained using a laser particle size analyzer and optical microscope. Examples 5, 6, and 9 were characterized using SEM, and the results are as follows: Figure 3 . Figure 2 and Figure 3 The results show that the nanocapsules exhibit a regular spherical shape, indicating that the preparation process of this invention can produce nanocapsules with uniform morphology; and there is no obvious agglomeration between the capsule particles, with good dispersion.

[0035] It should be understood that the various forms of processes shown above can be used to reorder, add, or delete steps. For example, the steps described in this invention disclosure can be executed in parallel, sequentially, or in different orders, as long as the desired result of the technical solution disclosed in this invention can be achieved, and this is not limited herein.

[0036] The specific embodiments described above do not constitute a limitation on the scope of protection of this invention. Those skilled in the art should understand that various modifications, combinations, sub-combinations, and substitutions can be made according to design requirements and other factors. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this invention should be included within the scope of protection of this invention.

Claims

1. A process for the preparation of polysaccharide-based nanocapsules, characterized in that: Specifically comprising the following steps: S1. The polysaccharide polymer aqueous solution and the target load oil phase solution are respectively transported by peristaltic pumps and pre-mixed to obtain a water-oil mixed system; S2. The water-oil mixed system obtained in step S1 is pushed by a peristaltic pump into a continuous flow ultrasonic environment for ultrasonic treatment, the ultrasonic power is 100-1000 W, and the ultrasonic time is 5-60 min; S3. The product at the equipment discharge port after ultrasonic treatment in step S2 is collected to obtain a polysaccharide-based nano-microcapsule dispersion liquid; drying treatment is performed to obtain a polysaccharide-based nano-microcapsule.

2. A process for the preparation of polysaccharide-based nano-microcapsules according to claim 1, characterized by: The polysaccharide polymer aqueous solution is a polysaccharide polymer aqueous solution or a thiol polysaccharide polymer aqueous solution, and the mass fraction of the polysaccharide polymer is 0.01-5%.

3. The method for preparing polysaccharide-based nano-microcapsules according to claim 1, characterized in that: The target load oil phase solution has a concentration of 0.1-10 mg / ml.

4. A process for the preparation of polysaccharide-based nano-microcapsules according to claim 3, characterized by: The target load is a fat-soluble active substance curcumin, quercetin, resveratrol, epigallocatechin gallate or lutein; and the target load oil phase solution is an ethyl acetate solution of the fat-soluble active substance curcumin, quercetin, resveratrol, epigallocatechin gallate or lutein.

5. The method of claim 1, wherein the method is characterized by: The rotation speed ratio of the two peristaltic pumps for transporting the polysaccharide polymer aqueous solution and the target load oil phase solution is 1:10-10:

1.

6. A process for the preparation of polysaccharide-based nano-microcapsules according to claim 5, characterized by: The rotation speed ratio of the two peristaltic pumps for transporting the polysaccharide polymer aqueous solution and the target load oil phase solution is 5:1-10:

1.

7. The method of claim 1, wherein the method is characterized by: The ultrasonic power in step S2 is 400-1000 W, and the ultrasonic time is 10-30 min.

8. The process for the preparation of polysaccharide based nano-microcapsules as claimed in claim 1, wherein: The drying treatment mode in step S3 is spray drying or freeze drying; and the particle size of the polysaccharide-based nano-microcapsule is 100-5000 nm.

9. A polysaccharide-based nanocapsule prepared by the method of claim 1, wherein the polysaccharide-based nanocapsule is characterized by: The particle size of the polysaccharide-based nano-microcapsule is 100-5000 nm.

Images