A multi-layer embedding areca alkaloid sustained-release system, and a preparation method and application thereof

Abstract

The application discloses a multi-layer embedding areca alkaloid sustained-release system and a preparation method and application thereof, relates to the technical field of areca alkaloid, and the sustained-release system comprises an areca alkaloid core layer, an antioxidation layer and a protective layer. The areca alkaloid sustained-release core layer is located in the innermost layer, the antioxidation layer is wrapped outside the sustained-release core layer, and the protective layer is wrapped outside the antioxidation layer. The areca alkaloid is wrapped by the sustained-release core layer, the antioxidation layer and the protective layer in sequence, can effectively resist the damage of gastric acid and other environmental conditions to the structure of the areca alkaloid, prevents the oxidation inactivation of the areca alkaloid, realizes the target of targeting the intestinal tract of the active areca alkaloid, and meanwhile, can avoid the contact of the areca alkaloid with other organ tissues, and reduces the side effects of the areca alkaloid.

Description

Technical Field

[0001] This invention relates to the field of arecoline technology, specifically to a multilayer encapsulated arecoline sustained-release system, its preparation method, and its applications. Background Technology

[0002] Arecoline is an active natural compound that, after ingestion, exerts various effects in the human body, including promoting colonic motility, anti-inflammation, stimulating nerve activity, and improving memory. It influences the gut microbiota and helps maintain overall health. However, it is important to note that arecoline intake should be moderately controlled to avoid negative effects. Excessive arecoline intake can cause oral diseases and reproductive toxicity. Therefore, to ensure an appropriate amount of arecoline enters the body and is released in the intestines, and to protect its activity and stability while providing a controlled release method to enhance its effects in the intestines, a multilayer encapsulated arecoline sustained-release system, its preparation method, and its applications are proposed to address the aforementioned problems. Summary of the Invention

[0003] The purpose of this invention is to overcome the shortcomings of the prior art and provide a multilayer encapsulated arecoline sustained-release system, its preparation method and application, which can maintain the activity of arecoline for a long time.

[0004] The present invention achieves the above objectives through the following technical solutions:

[0005] The first objective of this invention is to provide a multilayer encapsulated arecoline sustained-release system, wherein the arecoline sustained-release system comprises, from the inside out, an arecoline sustained-release core layer, an antioxidant layer, and a protective layer;

[0006] The arecoline sustained-release core layer is composed of arecoline and metal-organic framework (MOF) to controllably release arecoline; the antioxidant layer is a polyphenol-protein complex to prevent structural changes in arecoline during storage and digestion, thus maintaining its activity; and the protective layer is a polysaccharide layer to protect the active structure of arecoline in the acidic environment of the stomach, allowing it to reach the intestines and exert its effects.

[0007] A further improvement is that the metal-organic framework (MOF) is a zirconium-based MOF.

[0008] A further improvement is that the zirconium-based MOF is one of UiO-66-PDC and UiO-66-NH2.

[0009] A further improvement is that the polyphenol is at least one of catechin, gallic acid, chlorogenic acid, and ferulic acid, and the protein is at least one of soy protein isolate, pea protein, wheat gliadin, zein, and whey protein.

[0010] A further improvement is that the polysaccharide in the polysaccharide layer is at least one of citrus high-methoxyl pectin, gum arabic, sodium alginate, and xanthan gum.

[0011] The second objective of this invention is to provide a method for preparing the above-mentioned multilayer encapsulated arecoline sustained-release system, comprising the following steps:

[0012] (1) Dissolve arecoline in a solvent to obtain arecoline solution. Mix arecoline solution with metal-organic framework (MOF), stir thoroughly, filter or centrifuge, collect the precipitate, and vacuum dry the precipitate into powder to obtain arecoline sustained-release core layer powder.

[0013] (2) The arecoline sustained-release core layer powder is added to the polyphenol-protein complex and stirred at room temperature to form a complete antioxidant layer on the outside of the arecoline sustained-release core layer. The core layer-antioxidant layer powder is obtained by freeze drying.

[0014] (3) The core layer-antioxidant layer powder is mixed with polysaccharide aqueous solution and stirred at 40-55°C to form a protective layer on the outside of the arecoline sustained-release core layer-antioxidant layer complex. The final encapsulated material, i.e., the multilayer encapsulated arecoline sustained-release system, is obtained by freeze drying.

[0015] A further improvement is that, in step (1), the solvent includes any one of water, ethanol or ethyl acetate, and the mixed mass concentration of the metal-organic framework (MOF) is 1 wt%-5 wt%.

[0016] A further improvement is that, in step (2), the mass ratio of the arecoline sustained-release core layer powder to the polyphenol-protein complex is 10:1-20:1;

[0017] The preparation process of the polyphenol-protein complex is as follows: a polyphenol water / alcohol solution with a mass concentration of 5%-15% is dispersed and dissolved in a protein solution with a mass concentration of 10%-30% at a volume ratio of 1:2-1:5, reacted at room temperature, and then subjected to high-pressure homogenization or high-pressure microfluidic treatment to form a polyphenol-protein complex.

[0018] A further improvement is that, in step (3), the mass ratio of the core layer-antioxidant layer powder to the polysaccharide aqueous solution is 1:5-1:15;

[0019] The preparation process of the polysaccharide aqueous solution is as follows: dissolve the polysaccharide in deionized water, stir in a water bath, and prepare an aqueous solution with a mass concentration of 10%-30%.

[0020] The third objective of this invention is to provide the application of the above-mentioned multilayer encapsulated arecoline sustained-release system in the preparation of an active arecoline drug that targets the intestine.

[0021] The present invention has the following beneficial effects:

[0022] This multi-layered arecoline sustained-release system effectively reduces the irritation and damage of arecoline to the oral mucosa, protecting oral health. During digestion, it effectively protects the active structure of arecoline from damage by gastric acid and other environmental factors, ensuring its targeted action on the intestines and enhancing its physiological activity. The multi-layered encapsulation structure controls the release rate and location of arecoline, allowing it to exert its effects at specific sites in the body, achieving precise control over the target site of arecoline action. Furthermore, the multi-layered encapsulation structure allows for precise control of the arecoline release rate and dosage, reducing its adverse effects on the human body and possessing practical application value. This multi-layered encapsulation technology promotes the rational utilization of arecoline resources, offering health, environmental, and economic benefits. Detailed Implementation

[0023] The present application will now be described in further detail. It should be noted that the following specific embodiments are only used to further illustrate the present application and should not be construed as limiting the scope of protection of the present application. Those skilled in the art can make some non-essential improvements and adjustments to the present application based on the above application content.

[0024] 1. Materials

[0025] Unless otherwise specified, all reagents used in this experiment are conventional reagents and were prepared using deionized water. All instruments used are standard laboratory instruments, and all methods used in this experiment are standard methods in this field unless otherwise specified.

[0026] 2. Method

[0027] 2.1 Preparation process of multilayer encapsulated arecoline sustained-release system

[0028] 2.1.1 Preparation of arecoline sustained-release core layer

[0029] The sustained-release core layer is a composite porous material layer. Metal-organic frameworks (MOFs) are porous materials composed of metal ions / clusters and organic ligands. Zirconium-based MOFs are suitable for biological applications. Using zirconium (Zr) ion clusters as the center and different organic ligands, metal-organic frameworks such as UiO-66-PDC and UiO-66-NH2 can be synthesized for core layer encapsulation of arecoline.

[0030] UiO-66-PDC can be prepared by weighing 2,6-dicarboxylic acid and zirconium oxychloride octahydrate, adding formic acid, dissolving, adding deionized water, stirring until homogeneous, and refluxing for 3 hours. After obtaining a milky white mixture, centrifuge at 10000 rpm for 5 minutes, collect the precipitate, wash the precipitate with anhydrous ethanol with ultrasonic assistance, centrifuge at 6000 rpm for 10 minutes, collect the precipitate, and repeat three times. Then, dry in a vacuum drying oven at 30-40℃ to obtain UiO-66-PDC.

[0031] The preparation of UiO-66-NH2 involves weighing out a certain amount of 2-amino-14-phthalic acid and zirconium chloride, adding N,N-dimethylformamide (DMF) and glacial acetic acid as solvents, shaking to dissolve, adding deionized water, stirring evenly, and then carrying out an oil bath reaction. After the reaction is complete, the reaction solution is centrifuged at 10000 r / min for 8 min, the precipitate is collected, washed with anhydrous ethanol, and dried under vacuum at 30-40℃ to obtain UiO-66-NH2.

[0032] When encapsulating arecoline using MOF (Metal-Oxide-Factory), firstly, a certain amount of arecoline is dissolved in an appropriate solvent, such as water, ethanol, or ethyl acetate. Next, the arecoline solution is mixed with an appropriate amount of MOF composite material, with a concentration ranging from 1 wt% to 5 wt%. The mixture is stirred thoroughly at 300-600 rpm for 1-3 hours to ensure complete mixing and the formation of a uniform core layer. The mixture is then filtered or centrifuged at 6000-12000 rpm for 5-15 minutes, and the precipitate, i.e., the arecoline core layer, is collected. This arecoline core layer is then vacuum-dried at 30-50°C until it becomes powder. It should be noted that the numerical ranges of the above preparation conditions are not absolute and can be adjusted appropriately according to actual needs.

[0033] 2.1.2 Preparation of Antioxidant Layer

[0034] The antioxidant layer is a polyphenol-protein composite layer, wherein the polyphenols can be selected from catechins, gallic acid, chlorogenic acid, ferulic acid, etc. to achieve antioxidant properties, and the proteins can be selected from soy protein isolate, pea protein, wheat gliadin, zein, whey protein, etc. to achieve emulsification and film-forming properties.

[0035] For example, one or more of the following water / alcohol solutions with a mass concentration of 5%-15% catechin, gallic acid, ferulic acid, or chlorogenic acid are selected and dispersed in a volume ratio of 1:2-1:5 in one of the following protein solutions with a mass concentration of 10%-30%: soy protein isolate, pea protein, wheat gliadin, zein, whey protein, etc. The mixture is reacted at 300-600 r / min for 60-120 min at room temperature, and then subjected to high-pressure homogenization or high-pressure microfluidic treatment to form a polyphenol-protein complex.

[0036] The core layer powder was added to the polyphenol-protein complex (the mass-to-volume ratio of the core layer to the polyphenol-protein complex was 10:1-20:1), and the mixture was stirred at 300-600 rpm for 60-180 min at room temperature to form a complete antioxidant layer coating the arecoline-releasing core layer. The core layer-antioxidant layer powder was obtained by freeze-drying. It should be noted that the composition of the above composite layers can be adjusted according to the actual film-forming requirements. Specific step parameters may vary depending on the choice of materials.

[0037] 2.1.3 Preparation of protective layer

[0038] The protective layer is a polysaccharide layer, which can be made from citrus high-methoxyl pectin, gum arabic, sodium alginate, xanthan gum, etc. For example, prepare one or more of citrus high-methoxyl pectin, gum arabic, sodium alginate, and xanthan gum, dissolve them in a certain volume of deionized water, and stir thoroughly for 10-60 minutes at 30-50℃ water bath and 300-600 rpm to prepare an aqueous solution with a mass concentration of 10%-30%.

[0039] The core layer-antioxidant layer powder was mixed with a polysaccharide aqueous solution at a mass ratio of 1:5 to 1:15, and stirred at 300-600 rpm for 30-100 min at 40-55℃ until a protective layer was formed on the arecoline sustained-release core layer-antioxidant layer complex. The final encapsulation was obtained by freeze-drying.

[0040] 2.2 Effect Verification

[0041] 2.2.1 Acquisition of different multilayer encapsulated arecoline sustained-release systems

[0042] 2.2.1.1 Example 1

[0043] Preparation of UiO-66-PDC composite material: Weigh 10g of 2,6-dicarboxylic acid and 2g of zirconium oxychloride octahydrate, add 50mL of formic acid, dissolve, then add 100mL of deionized water, and reflux and heat for 3h. After obtaining a milky white mixture, centrifuge at 10000r / min for 5min, collect the precipitate, wash with anhydrous ethanol, and dry under vacuum at 35℃ to obtain UiO-66-PDC.

[0044] Preparation of arecoline core layer: Weigh 10g arecoline, dissolve it in 100mL ethanol, mix it with 3g UiO-66-PDC composite material, react at 500r / min for 2.5h, centrifuge at 12000r / min for 10min or filter through a filter membrane to collect the precipitate, and vacuum dry at 35℃ to powder.

[0045] Preparation of the antioxidant layer: 0.5g of gallic acid was dissolved in deionized water to prepare a 10% solution, and 10g of soy protein isolate was dissolved in deionized water to prepare a 20% solution. The two solutions were mixed evenly at a volume ratio of 1:2, and then subjected to high-pressure homogenization and microfluidic treatment to form a polyphenol-protein complex. The core layer powder was added to the polyphenol-protein complex (the mass ratio of core layer to polyphenol-protein complex was 20:1), and reacted at 450 rpm for 100 min at room temperature to form a complete antioxidant layer encapsulating the arecoline-releasing core layer. The core layer-antioxidant layer powder was obtained by freeze-drying.

[0046] Preparation of the protective layer: Weigh 10g of citrus high-methoxyl pectin and dissolve it in 50mL of deionized water. Heat and stir at 45℃ until completely dissolved to prepare a 20% solution. Dissolve 10g of the previously prepared antioxidant layer powder in 100mL of the citrus high-methoxyl pectin solution. Stir at 350r / min at 40℃ for 80min until a protective layer forms on the arecoline sustained-release core-antioxidant layer complex. Freeze-dry for 54h to obtain the final encapsulation.

[0047] 2.2.1.2 Example 2

[0048] Preparation of UiO-66-NH2 composite material: A certain amount of 2-amino-14-phthalic acid and zirconium chloride were weighed, added to the solvents DMF and glacial acetic acid, and dissolved by shaking. Deionized water was then added, and the mixture was stirred until homogeneous before reacting in an oil bath for 1 hour. After the reaction was complete, the reaction solution was centrifuged at 6000 r / min, and the precipitate was collected. This process was repeated three times: washing with anhydrous ethanol with ultrasonic assistance and centrifuging at 6000 r / min. The precipitate was then dried in a vacuum drying oven at 40℃ to obtain UiO-66-NH2.

[0049] Preparation of arecoline core layer: Weigh 10g arecoline, dissolve it in 100mL of deionized water, mix it with 2g of UiO-66-NH2 composite material, react at 500r / min for 2h, centrifuge at 8000r / min for 12min or filter through a filter membrane to collect the precipitate, and vacuum dry at 35℃ to powder.

[0050] Preparation of the antioxidant layer: Weigh 3g of chlorogenic acid and 5g of ferulic acid and dissolve them in ethanol to prepare a 15% solution. Weigh 4g of wheat gliadin and 6g of zein and dissolve them in ethanol to prepare a 12% solution. Mix the two solutions at a volume ratio of 1:2. Homogenize the mixture under high pressure at 150 MPa to form a polyphenol-protein complex. Add the prepared arecoline sustained-release core layer powder to the polyphenol-protein complex (the mass ratio of core layer to polyphenol-protein complex is 20:1). React at room temperature at 350 rpm for 120 min to form a complete antioxidant layer encapsulating the arecoline sustained-release core layer.

[0051] Preparation of the protective layer: Weigh 10g of gum arabic and dissolve it in 40mL of deionized water. Heat in a 50℃ water bath and stir at 500r / min until completely dissolved, preparing a 25% solution. Mix 10g of the previously prepared antioxidant powder with 100mL of the gum arabic solution and stir at 350r / min for 50min at 40℃ until a protective layer forms on the arecoline sustained-release core-antioxidant complex. Freeze-dry for 48h to obtain the final encapsulation.

[0052] 2.2.1.3 Example 3

[0053] Preparation of UiO-66-PDC composite material: 10g of 2,6-dicarboxylic acid and 2g of zirconium oxychloride octahydrate were weighed, dissolved in 50mL of formic acid, and 100mL of deionized water were added. After stirring evenly, the mixture was refluxed and heated for 3h. After obtaining a milky white mixture, it was centrifuged at 10000r / min for 5min, the precipitate was collected, washed with anhydrous ethanol, and dried under vacuum at 35℃ to obtain UiO-66-PDC.

[0054] Preparation of arecoline core layer: Weigh 10g arecoline, dissolve it in 100mL ethanol, mix it with 1g UiO-66-PDC composite material, react at 500r / min for 1h, centrifuge at 8000r / min for 15min or filter through a filter membrane to collect the precipitate, and vacuum dry at 35℃ to powder.

[0055] Preparation of the antioxidant layer: 12g of catechin was dissolved in deionized water to prepare a 12% solution, and 10g of whey protein was dissolved in deionized water to prepare a 10% solution. The two were mixed uniformly at a volume ratio of 1:2. The mixture was then treated with a high-pressure microfluidic jet at 135 MPa to form a polyphenol-protein complex. The prepared arecoline sustained-release core layer powder was added to the polyphenol-protein complex (the mass ratio of the core layer to the polyphenol-protein complex was 12:1), and the mixture was reacted at 350 r / min for 90 min at room temperature to form a complete antioxidant layer encapsulating the UiO-66-PDC core layer.

[0056] Preparation of the protective layer: Weigh 12g of sodium alginate and dissolve it in 50mL of deionized water. Stir at 450rpm in a 50℃ water bath until completely dissolved, preparing a 24% solution. Mix 10g of the previously prepared antioxidant powder with 80mL of polysaccharide aqueous solution. Stir at 350rpm for 80min at 40℃ until a protective layer forms outside the core-antioxidant complex. Obtain the final embedded material by freeze-drying for 48h.

[0057] 2.2.1.4 Example 4

[0058] Preparation of UiO-66-NH2 composite material: A certain amount of 2-amino-14-phthalic acid and zirconium chloride were weighed, added to the solvents DMF and glacial acetic acid, and dissolved by shaking. Deionized water was then added, and the mixture was stirred until homogeneous before reacting in an oil bath for 1 hour. After the reaction was complete, the reaction solution was centrifuged at 6000 r / min, and the precipitate was collected. This process was repeated three times: washing with anhydrous ethanol with ultrasonic assistance and centrifuging at 6000 r / min. The precipitate was then dried in a vacuum drying oven at 40℃ to obtain UiO-66-NH2.

[0059] Preparation of arecoline core layer: Weigh 8g arecoline, dissolve it in 100mL ethanol, mix it with 2g UiO-66-NH2 composite material, react at 500r / min for 2h, centrifuge at 10000r / min for 15min or filter the mixture through a filter membrane to collect the precipitate, and dry it with hot air at 40℃ to powder.

[0060] Preparation of the antioxidant layer: Weigh 10g of catechin and dissolve it in deionized water to prepare a 15% solution. Weigh 10g of pea protein and dissolve it in deionized water to prepare a 20% solution. Mix the two solutions at a volume ratio of 1:2. Homogenize the mixture under high pressure at 150 MPa to form a polyphenol-protein complex. Add the prepared arecoline sustained-release core layer powder to the polyphenol-protein complex (the mass ratio of the core layer to the polyphenol-protein complex is 10:1). React at room temperature at 400 rpm for 100 min to form a complete antioxidant layer encapsulating the arecoline sustained-release core layer.

[0061] Preparation of the protective layer: Weigh 10g of xanthan gum and dissolve it in 50mL of deionized water. Heat in a 50℃ water bath at 450r / min until completely dissolved, preparing a 20% solution. Mix 10g of the previously prepared antioxidant powder with 100mL of gum arabic solution and stir at 350r / min for 60min at 40℃ until a protective layer forms on the arecoline sustained-release core-antioxidant complex. Freeze-dry for 48h to obtain the final encapsulation.

[0062] 2.2.2 In vitro gastrointestinal tract simulated digestion experiment

[0063] The bioavailability of arecoline embeddings in Examples 1-4 was compared using in vitro gastric, small intestinal, and colon models.

[0064] Specifically, the following methods were used: Following the reference method (Yajuan Bai, Yue Zhou, Ruifen Zhang, Yanxia Chen, Fengzhong Wang, Zhang, Mingwei Zhang. Gut microbial fermentation promotes the intestinal anti-inflammatory activity of Chinese yam polysaccharides. Food Chemistry, 2023, 402, 134003), in vitro simulated gastric digestive fluid, small intestinal digestive fluid, and human fecal fermentation broth were prepared. Arecoline encapsulated materials from Examples 1-4 were placed in these experimental solutions and reacted for 2 hours, 4 hours, and 12 hours respectively. After the reaction, the arecoline content in the reaction solution was measured, and the arecoline release effect of the encapsulated material in the stomach, small intestine, and colon was calculated. The results are shown in Table 1.

[0065] Table 1. Arecoline release rate from arecoline-encapsulated compounds in the stomach, small intestine, and colon in vitro.

[0066]

[0067] As shown in Table 1, after 2 hours of simulated gastric digestion in Examples 1, 2, 3, and 4, the arecoline release rate was less than 10%, indicating that the encapsulation technology can effectively protect arecoline release in a low pH environment. After 4 hours of simulated small intestinal digestion in Examples 1, 2, 3, and 4, the arecoline release rate was less than 15%, indicating that the encapsulation technology can effectively protect arecoline release in a protease-rich environment. After 12 hours of simulated colonic fermentation in Examples 1, 2, 3, and 4, the arecoline release rate was greater than 85%, indicating that the encapsulation technology can effectively protect most of the arecoline from passing through the stomach and small intestine, reaching the target site in the colon for effective release. This effectively protects the active structure of arecoline from damage by gastric acid and other environmental factors, protecting its active structure to target the intestine and improve physiological activity, which is of great significance for the preparation of arecoline-targeted drugs.

[0068] 2.2.3 Comparative Experiment on the Effect of Multi-Layer Embedding

[0069] The effects of each layer of embedding material on the arecoline embedding effect in Example 4, which showed the best embedding effect, were compared using in vitro gastric, small intestine, and colon models.

[0070] Specifically, the comparative examples of Example 4 are as follows: Comparative Example 1: Arecoline; Comparative Example 2: Arecoline sustained-release core layer; Comparative Example 3: Arecoline sustained-release core layer + antioxidant layer; Comparative Example 4: Arecoline sustained-release core layer + polysaccharide layer. The same in vitro simulated gastric digestive fluid, small intestinal digestive fluid, and human fecal fermentation broth were prepared. The arecoline encapsulated material of Example 4 and Comparative Examples 1-4 were placed in the above experimental solutions and reacted for 2 hours, 4 hours, and 12 hours, respectively. After the reaction, the arecoline content in the reaction solution was measured, and the arecoline release effect of the encapsulated material in the stomach, small intestine, and colon was calculated. The results are shown in Table 2.

[0071] Table 2. Arecoline release rate from arecoline-encapsulated compounds in the stomach, small intestine, and colon in vitro.

[0072]

[0073] Note: In Comparative Example 1, the release rate of arecoline in simulated gastric digestive fluid was 100%, and it could not be detected subsequently, so it is indicated by "-".

[0074] Table 2 shows that after 2 hours of simulated gastric digestion in comparison examples 1, 2, and 3, the arecoline release rate was greater than 35%, indicating a certain protective effect on arecoline. However, the arecoline release rate was significantly higher than that of example 4, while the arecoline release rate of comparison example 4 was similar to that of example 4, suggesting that the polysaccharide layer plays an important protective role for arecoline in a low pH environment. After simulated gastric and small intestinal digestion in comparison example 4, there was no significant difference in the arecoline release rate between comparison example 4 and example 4, indicating that the polysaccharide layer is an important material for protecting arecoline in its active form as it passes through the stomach and small intestine to reach the colon. After 12 hours of simulated colonic fermentation, the arecoline release rate of comparison example 4 was significantly lower than that of example 4, indicating that the antioxidant layer formed by the phenol-protein complex plays an important role in maintaining the active form of arecoline. Based on the above verifications, the multilayer encapsulation technology of arecoline sustained-release core layer + antioxidant layer + polysaccharide layer can effectively protect most of the arecoline as it passes through the gastric and small intestinal digestive tract, ensuring effective release after reaching the target site in the colon. This is of great significance for the preparation of drugs that target the intestine with arecoline.

[0075] The embodiments described above are merely examples of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention.

Claims

1. A multilayer encapsulated arecoline sustained-release system, characterized in that, The arecoline sustained-release system targets the human intestine, and the arecoline sustained-release system comprises, from the inside out, an arecoline sustained-release core layer, an antioxidant layer, and a protective layer. The arecoline sustained-release core layer is composed of arecoline and a metal-organic framework (MOF), wherein the metal-organic framework (MOF) is a zirconium-based MOF. The antioxidant layer is a polyphenol-protein composite layer, wherein the polyphenol is at least one of catechin, gallic acid, chlorogenic acid, and ferulic acid, and the protein is at least one of soy protein isolate, pea protein, wheat gliadin, zein, and whey protein. The protective layer is a polysaccharide layer, which is at least one of citrus high-methoxyl pectin, gum arabic, sodium alginate, and xanthan gum.

2. The multilayer encapsulated arecoline sustained-release system according to claim 1, characterized in that: The zirconium-based MOF is one of UiO-66-PDC and UiO-66-NH2.

3. A method for preparing a multilayer encapsulated arecoline sustained-release system according to any one of claims 1-2, characterized in that: Includes the following steps: (1) Dissolve arecoline in a solvent to obtain arecoline solution. Mix arecoline solution with metal-organic framework (MOF), stir thoroughly, filter or centrifuge, collect the precipitate, and vacuum dry the precipitate into powder to obtain arecoline sustained-release core layer powder. (2) Add the arecoline sustained-release core layer powder to the polyphenol-protein complex and continue stirring at room temperature to form a complete antioxidant layer on the outside of the arecoline sustained-release core layer, and obtain the core layer-antioxidant layer powder by freeze drying. (3) The core layer-antioxidant layer powder is mixed with polysaccharide aqueous solution and stirred at 40-55°C to form a protective layer on the outside of the arecoline sustained-release core layer-antioxidant layer complex. The final encapsulated material is obtained by freeze drying, namely the multilayer encapsulated arecoline sustained-release system.

4. The method for preparing a multilayer encapsulated arecoline sustained-release system according to claim 3, characterized in that: In step (1), the solvent includes any one of water, ethanol or ethyl acetate, and the mixed mass concentration of the metal-organic framework (MOF) is 1wt%-5wt%.

5. The method for preparing a multilayer encapsulated arecoline sustained-release system according to claim 3, characterized in that: In step (2), the mass ratio of the arecoline sustained-release core layer powder to the polyphenol-protein complex is 10:1-20:1; The preparation process of the polyphenol-protein complex is as follows: a polyphenol water / alcohol solution with a mass concentration of 5%-15% is dispersed and dissolved in a protein solution with a mass concentration of 10%-30% at a volume ratio of 1:2-1:5, reacted at room temperature, and then subjected to high-pressure homogenization or high-pressure microfluidic treatment to form a polyphenol-protein complex.

6. The method for preparing a multilayer encapsulated arecoline sustained-release system according to claim 3, characterized in that: In step (3), the mass ratio of the core layer-antioxidant layer powder to the polysaccharide aqueous solution is 1:5-1:15; The preparation process of the polysaccharide aqueous solution is as follows: dissolve the polysaccharide in deionized water, stir in a water bath, and prepare an aqueous solution with a mass concentration of 10%-30%.

7. The use of the multilayer encapsulated arecoline sustained-release system according to any one of claims 1-2 in the preparation of an active arecoline drug that targets the intestine.

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