Chitosan coated gamma-cyclodextrin metal organic framework delivery system as well as preparation method and application thereof

Abstract

According to the chitosan-coated gamma-cyclodextrin metal organic framework delivery system and the preparation method and application thereof, hippophae rhamnoides polyphenol serving as an active component is efficiently loaded through a hydrophobic cavity of the chitosan-coated gamma-cyclodextrin metal organic framework delivery system, and encapsulation and release of the hippophae rhamnoides polyphenol can be achieved through the hydrophilic surface of the chitosan-coated gamma-cyclodextrin metal organic framework delivery system; chitosan is adopted as a protective layer to coat the cyclodextrin metal organic framework and the sea-buckthorn polyphenol, so that the carrier and the active components are prevented from being damaged by gastric acid and small intestine digestive enzymes, and the sea-buckthorn polyphenol can be accurately positioned to the colon part through the targeted positioning effect of the chitosan, so that the treatment on the colitis is realized, and the treatment effect is good. The invention provides a more effective and safer inflammation treatment means.

Description

Technical Field The present invention belongs to the field of biomedicine technology, and in particular relates to a chitosan-coated gamma-cyclodextrin metal organic framework delivery system and a preparation method and application thereof. Background Art Seabuckthorn (scientific name: Hippophae rhamnoides), also known as sand date and vinegar willow, is a deciduous shrub or small tree of the Elaeagnaceae family. Seabuckthorn polyphenols, as a class of natural compounds extracted from seabuckthorn, mainly include flavonoids, phenolic acids and other polyphenols with biological activity. They are widely present in the fruits, leaves and seeds of seabuckthorn and are one of the important functional components of seabuckthorn. Modern medical research shows that seabuckthorn polyphenols can reduce the production of proinflammatory cytokines (such as TNF-α) by inhibiting key molecules in the inflammatory signaling pathway such as COX-2 (cyclooxygenase-2), thereby alleviating inflammation in the colon.

[0003] At present, commonly used carriers for loading active ingredients include nanosystems, hydrogels, cyclodextrin-metal organic frameworks, etc. However, the targeting of nanoparticles and nanocapsules may be limited by the biological barriers and clearance mechanisms in the body, resulting in the inability to accurately deliver the active ingredients to the colon. The release rate and biodegradability of hydrogels may also affect their stability and durability in the body. The physical structure of cyclodextrin-metal organic frameworks is fragile, highly soluble in aqueous solutions, and easily degraded or destroyed in the body, resulting in reduced release and bioavailability of active ingredients.

[0004] Therefore, although sea buckthorn polyphenols have potential therapeutic value, how to accurately deliver sea buckthorn polyphenols to the colon and ensure the bioavailability of sea buckthorn polyphenols remains a difficult problem. Summary of the invention The purpose of the present invention is to provide a chitosan-coated γ-cyclodextrin metal organic framework delivery system to solve the current problem of difficulty in transporting seabuckthorn polyphenols in the body.

[0006] The present invention is achieved by the following technical solutions: The chitosan-coated gamma-cyclodextrin metal organic framework delivery system comprises a cyclodextrin metal organic framework used as a carrier, seabuckthorn polyphenol loaded on the cyclodextrin metal organic framework, and chitosan coating the cyclodextrin metal organic framework and the seabuckthorn polyphenol.

[0007] The present invention adopts a cyclodextrin metal organic framework with dual properties as a carrier, and efficiently loads seabuckthorn polyphenol as an active component through its hydrophobic cavity, and can achieve the encapsulation and release of seabuckthorn polyphenol through its hydrophilic surface; chitosan is then used as a protective layer to coat the cyclodextrin metal organic framework and seabuckthorn polyphenol, thereby ensuring that the carrier and the active component are protected from damage by gastric acid and small intestinal digestive enzymes, and through the targeted positioning effect of chitosan, the seabuckthorn polyphenol can be accurately positioned to the colon.

[0008] Preferably, the method for preparing the cyclodextrin metal organic framework comprises the following steps: S11, dissolving: adding cyclodextrin and alkali metal cations to deionized water in proportion, dissolving with the aid of ultrasound to obtain a mixed stock solution; S12, filtration: filtering the mixed stock solution in step S11 using an organic filter membrane to obtain a filtrate; S13, diffusion crystallization: the filtrate in step S12 is transferred to a small container, and the small container is placed in a sealed container filled with methanol at room temperature for natural diffusion and crystallization to obtain crude crystals; S14, impurity removal: collecting the crude crystals described in step S13, washing the crude crystals with methanol, and then immersing them with dichloromethane to obtain pure crystals; S15, drying: placing the pure crystals in step S14 in a vacuum drying oven for drying to obtain a cyclodextrin metal organic framework.

[0009] The present invention uses cyclodextrin as an organic ligand and alkali metal cations as coordinating ions, and obtains high-purity and high-stability cyclodextrin metal organic frameworks (CD-MOFs) through methanol vapor diffusion method. Such CD-MOFs can improve the solubility of seabuckthorn polyphenols and be used as a carrier for controlled or sustained release. Furthermore, it has a hydrophobic cavity and a hydrophilic surface, which can load and deliver the active component seabuckthorn polyphenols, thereby achieving encapsulation, protection and controlled release of the active component, thereby improving the stability, bioavailability and therapeutic effect of the active component.

[0010] Preferably, the cyclodextrin in step S11 is γ-cyclodextrin, and the alkali metal cation is potassium ion.

[0011] Specifically, the γ-cyclodextrin has a larger cavity size, which can accommodate more hydrophobic seabuckthorn polyphenols and improve the solubility of seabuckthorn polyphenols. The potassium ions can form coordination bonds with the oxygen atoms in the γ-cyclodextrin, enhance the stability of the delivery skeleton, and prevent it from premature degradation in the body. Furthermore, in the alkaline environment of the colon, both γ-cyclodextrin and potassium ions have good stability, so that the delivery skeleton can remain intact in the colon, thereby achieving the release of seabuckthorn polyphenols.

[0012] Preferably, the specification of the organic filter membrane in step S12 is 0.45 μm.

[0013] Specifically, filtering the mixed stock solution with a 0.45μm organic filter membrane can effectively remove the incompletely dissolved cyclodextrin, alkali metal cation precipitates or other insoluble impurities in the solution, thereby reducing the occurrence of side reactions and improving the purity and yield of CD-MOFs. The filtered samples are easier to characterize various physical and chemical properties, such as X-ray diffraction (XRD), scanning electron microscopy (SEM), etc.

[0014] Preferably, the crystallization temperature in step S13 is 25-100° C. More preferably, the crystallization temperature in step S13 is 50° C.

[0015] Specifically, a complete organic metal framework can be generated in methanol vapor at 25-100°C. Since the nucleation rate is inversely proportional to the temperature during the crystallization process, the number of nucleation sites formed decreases as the temperature increases. Therefore, the higher the crystallization temperature, the larger the crystal size, and the lower the yield of MOFs. While appropriately increasing the temperature helps to quickly form crystal nuclei, 50°C is preferred as the crystallization temperature, considering the crystal quality, material cost and time cost.

[0016] In addition, step S14 uses a non-polar organic solvent, dichloromethane, to immerse the crude crystals, which can remove unreacted cyclodextrin, residual alkali metal ions and some by-products, and can also gradually replace the methanol solvent molecules in the crystals, reducing the residual solvent content in the crystals, thereby improving the purity and performance stability of MOFs, while ensuring the integrity of the MOFs structure to prevent impurities from clogging the pores of MOFs and affecting subsequent operations and applications.

[0017] The present invention also aims to provide a method for preparing a chitosan-coated γ-cyclodextrin metal organic framework delivery system.

[0018] The preparation method of the chitosan-coated γ-cyclodextrin metal organic framework delivery system comprises the following steps: S1. Loading: uniformly mixing the cyclodextrin metal organic framework and the anhydrous ethanol solution of seabuckthorn polyphenol to obtain a mixed solution, and subjecting the mixed solution to ultrasonic treatment; S2, centrifugal collection: centrifuging the mixed solution treated with ultrasound in step S1, discarding the supernatant to obtain a load, washing the load with anhydrous ethanol, collecting the load and vacuum drying to obtain a cyclodextrin metal organic framework-sea buckthorn polyphenol complex; S3, coating: gradually adding the cyclodextrin metal organic framework-sea buckthorn polyphenol complex described in step S2 to the chitosan acetic acid solution to obtain a mixture, subjecting the mixture to ultrasonic treatment, using the mixture as an aqueous phase, and keeping it warm for later use; S4, emulsification and dispersion: under low-speed stirring, slowly drip the water phase in step S3 into the oil phase using a syringe, and after the water phase is dripped, stir and emulsify to obtain an emulsion; S5, cross-linking: adding a cross-linking agent to the emulsion in step S4 for cross-linking and curing. After the curing is completed, centrifugation is performed and the supernatant is discarded to obtain coarse microspheres; S6, washing and drying: the crude microspheres described in step S5 are repeatedly washed with petroleum ether, isopropanol and ultrapure water, respectively, filtered and vacuum dried to obtain a chitosan-coated γ-cyclodextrin metal organic framework delivery system.

[0019] The present invention uses natural carbohydrate cyclodextrin and alkali metal cations as raw materials, adopts methanol vapor diffusion method to synthesize cyclodextrin metal organic frameworks (CD-MOFs), adopts impregnation method to load seabuckthorn polyphenols into the cavity of CD-MOF to form a host-guest structure, and finally adopts emulsification dispersion cross-linking method to modify the system into microspheres with chitosan (CS) to obtain a stable CS-CD-MOFs delivery system.

[0020] Preferably, in step S1, the loading rate of seabuckthorn polyphenol in the cyclodextrin metal organic framework is greater than 20%.

[0021] Specifically, the bioavailability of seabuckthorn polyphenols is improved by ensuring the loading rate of the seabuckthorn polyphenols, thereby ensuring that the seabuckthorn polyphenols can effectively exert their anti-inflammatory effects when being transported to the colon.

[0022] Preferably, the method for preparing the anhydrous ethanol solution of seabuckthorn polyphenol in step S1 is: adding seabuckthorn polyphenol into a 2 mg / ml ethanol solution and fully dissolving it.

[0023] Specifically, seabuckthorn polyphenols, as a natural plant extract, are hydrophobic. The use of anhydrous ethanol, an organic solvent, can efficiently dissolve seabuckthorn polyphenols to obtain a uniformly distributed anhydrous ethanol solution of seabuckthorn polyphenols, thereby increasing the subsequent loading rate of seabuckthorn polyphenols in CD-MOFs. In addition, anhydrous ethanol has good compatibility with CD-MOFs and will not affect the structure and performance of CD-MOFs.

[0024] Preferably, the insulation temperature of the water phase in step S3 and the oil phase in step S4 is 40°C.

[0025] Preferably, the oil phase in step S4 is liquid paraffin containing Span-80.

[0026] Specifically, by using liquid paraffin as the oil phase, it has low volatility and high chemical stability, can provide a stable oil phase environment, and can also serve as a protective layer to isolate the active components in the water phase from the external environment. By adding non-ionic emulsifier Span-80 to the oil phase, the interfacial tension between the water phase and the oil phase can be reduced, promoting the mixing and emulsification of the two.

[0027] Preferably, the cross-linking agent in step S5 is glutaraldehyde, and the concentration of the glutaraldehyde is 50%.

[0028] Preferably, the cross-linking and curing time in step S5 is 2-2.5 hours.

[0029] The present invention also aims to provide an application of a chitosan-coated γ-cyclodextrin metal organic framework delivery system.

[0030] The chitosan-coated cyclodextrin metal organic framework delivery system is used in the treatment of colon inflammation.

[0031] The beneficial effects of the present invention are as follows: The present invention adopts a cyclodextrin metal organic framework with dual properties as a carrier, and efficiently loads seabuckthorn polyphenol as an active component through its hydrophobic cavity, and can achieve the encapsulation and release of seabuckthorn polyphenol through its hydrophilic surface; chitosan is then used as a protective layer to coat the cyclodextrin metal organic framework and seabuckthorn polyphenol, thereby ensuring that the carrier and the active component are protected from damage by gastric acid and small intestinal digestive enzymes, and through the targeted positioning effect of chitosan, the seabuckthorn polyphenol can be accurately positioned to the colon.

[0032] The present invention uses natural carbohydrate cyclodextrin and alkali metal cations as raw materials, adopts methanol vapor diffusion method to synthesize cyclodextrin metal organic frameworks (CD-MOFs), adopts impregnation method to load seabuckthorn polyphenols into the cavity of CD-MOF to form a host-guest structure, and finally adopts emulsification dispersion cross-linking method to modify the system into microspheres with chitosan (CS) to obtain a stable CS-CD-MOFs delivery system.

[0033] The chitosan-coated cyclodextrin metal organic framework delivery system of the present invention can achieve the treatment of colon inflammation by targeted release of seabuckthorn polyphenols, thereby providing a more effective and safer means of treating inflammation. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is the SEM image of γ-CD-MOFs; Figure 2 is the SEM image of Example 1; Figure 3 This is the SEM image of Example 2. DETAILED DESCRIPTION The specific technical scheme of the present invention is described below in conjunction with Examples 1-2: The preparation method of γ-cyclodextrin metal organic framework comprises the following steps: S11, dissolving: adding 1.297 g of γ-cyclodextrin and 0.448 g of potassium ions in a ratio of 1:8 mol to 20 mL of deionized water, and dissolving by ultrasound to obtain a mixed stock solution; S12, filtration: filtering the mixed stock solution in step S11 using a 0.45 μm organic filter membrane to obtain a filtrate; S13, diffusion crystallization: the filtrate in step S12 is transferred to a small container, and the small container is placed in a sealed container filled with 50 mL of methanol at room temperature for natural diffusion and crystallization for 2-3 days to obtain crude crystals; S14, impurity removal: collect the crude crystals described in step S13, wash the crude crystals with 15 mL of methanol for 3 times, and then immerse them in dichloromethane for 2 days to obtain pure white and clean crystals; S15, drying: placing the pure crystals in step S14 in a 50° C. vacuum drying oven for 24 hours to obtain a γ-cyclodextrin metal organic framework.

[0036] The preparation method of α-cyclodextrin metal organic framework comprises the following steps: S11, dissolving: adding 0.973 g of α-cyclodextrin and 0.448 g of potassium ions in a ratio of 1:8 mol to 20 mL of deionized water, and dissolving by ultrasound to obtain a mixed stock solution; S12, filtration: filtering the mixed stock solution in step S11 using a 0.45 μm organic filter membrane to obtain a filtrate; S13, diffusion crystallization: the filtrate in step S12 is transferred to a small container, and the small container is placed in a sealed container filled with 50 mL of methanol at room temperature for natural diffusion and crystallization for 2-3 days to obtain crude crystals; S14, impurity removal: collect the crude crystals described in step S13, wash the crude crystals with 15 mL of methanol for 3 times, and then immerse them in dichloromethane for 2 days to obtain pure white and clean crystals; S15, drying: placing the pure crystals in step S14 in a 50° C. vacuum drying oven for 24 hours to obtain an α-cyclodextrin metal organic framework.

[0037] The preparation method of the anhydrous ethanol solution of seabuckthorn polyphenol is as follows: 20 mg of seabuckthorn polyphenol is added into 10 mL of 2 mg / ml ethanol solution and fully dissolved.

[0038] The preparation method of chitosan acetic acid solution is as follows: 0.3 g of chitosan is added into 20 mL of 2% acetic acid solution and fully dissolved to obtain 15 g / mL chitosan acetic acid solution.

[0039] Example 1 The preparation method of the chitosan-coated γ-cyclodextrin metal organic framework delivery system comprises the following steps: S1. Loading: uniformly mix 100 mg of cyclodextrin metal organic framework and 10 ml of seabuckthorn polyphenol anhydrous ethanol solution to obtain a mixed solution, and perform ultrasonic treatment on the mixed solution at 60° C.; S2, centrifugal collection: centrifuge the mixed solution treated with ultrasound in step S1 at 4500 r / min for 10 min, discard the supernatant to obtain a load, wash the load twice with anhydrous ethanol, collect the load and vacuum dry it at 50° C. to obtain a cyclodextrin metal organic framework-sea buckthorn polyphenol complex; S3, coating: gradually adding the cyclodextrin metal organic framework-sea buckthorn polyphenol complex described in step S2 into the 15 g / mL chitosan acetic acid solution to obtain a mixture, subjecting the mixture to ultrasonic treatment, using the mixture as an aqueous phase, and keeping it warm at 40° C. for later use; S4, emulsification and dispersion: under low-speed stirring, slowly drip the aqueous phase of step S3 into the liquid paraffin containing Span-80 using a syringe, and after the aqueous phase is dripped, stir and emulsify to obtain an emulsion; S5, cross-linking: adding 50% glutaraldehyde to the emulsion in step S4 for cross-linking curing for 2 hours. After curing, centrifuging at 4000 r / min for 15 minutes, discarding the supernatant, and obtaining coarse microspheres; S6, washing and drying: the crude microspheres described in step S5 are repeatedly washed three times with petroleum ether, isopropanol and ultrapure water respectively, filtered, and vacuum dried for 24 hours to obtain a chitosan-coated γ-cyclodextrin metal organic framework delivery system.

[0040] Example 2 The preparation method of the chitosan-coated γ-cyclodextrin metal organic framework delivery system comprises the following steps: S1. Loading: 100 mg of cyclodextrin metal organic framework and 10 ml of seabuckthorn polyphenol anhydrous ethanol solution were placed in a 50 mL container and mixed evenly, and oscillated at 40° C. for 48 h using a constant temperature water bath oscillator to obtain a mixed solution; S2, centrifugal collection: centrifuge the mixed solution treated with ultrasound in step S1 at 4500 r / min for 10 min, discard the supernatant to obtain a load, wash the load twice with anhydrous ethanol, collect the load and vacuum dry it at 50° C. to obtain a cyclodextrin metal organic framework-sea buckthorn polyphenol complex; S3, coating: gradually adding the cyclodextrin metal organic framework-sea buckthorn polyphenol complex described in step S2 into the 15 g / mL chitosan acetic acid solution to obtain a mixture, subjecting the mixture to ultrasonic treatment, using the mixture as an aqueous phase, and keeping it warm at 40° C. for later use; S4, emulsification and dispersion: under low-speed stirring, slowly drip the aqueous phase of step S3 into the liquid paraffin containing Span-80 using a syringe, and after the aqueous phase is dripped, stir and emulsify to obtain an emulsion; S5, cross-linking: adding 50% glutaraldehyde to the emulsion in step S4 for cross-linking curing for 2 hours. After curing, centrifuging at 4000 r / min for 15 minutes, discarding the supernatant, and obtaining coarse microspheres; S6, washing and drying: the crude microspheres described in step S5 are repeatedly washed three times with petroleum ether, isopropanol and ultrapure water respectively, filtered, and vacuum dried for 24 hours to obtain a chitosan-coated γ-cyclodextrin metal organic framework delivery system.

[0041] Comparative Example 1 The preparation method of the γ-cyclodextrin metal organic framework delivery system comprises the following steps: S1, preparation of γ-cyclodextrin metal organic framework; S2, loading: 100 mg of γ-cyclodextrin metal organic framework and 10 ml of seabuckthorn polyphenol anhydrous ethanol solution were uniformly mixed to obtain a mixed solution, and the mixed solution was subjected to ultrasonic treatment at 60° C.; S3, centrifugal collection: centrifuge the mixed solution treated with ultrasound in step S3 at 4500 r / min for 10 min, discard the supernatant to obtain a load, wash the load twice with anhydrous ethanol, collect the load and vacuum dry it at 50° C. to obtain a γ-cyclodextrin metal organic framework-sea buckthorn polyphenol complex.

[0042] Comparative Example 2 The preparation method of the α-cyclodextrin metal organic framework delivery system comprises the following steps: S1, preparation of α-cyclodextrin metal organic framework; S2, loading: 100 mg of γ-cyclodextrin metal organic framework and 10 ml of seabuckthorn polyphenol anhydrous ethanol solution were uniformly mixed to obtain a mixed solution, and the mixed solution was subjected to ultrasonic treatment at 60° C.; S3, centrifugal collection: centrifuge the mixed solution treated with ultrasound in step S3 at 4500 r / min for 10 min, discard the supernatant to obtain a load, wash the load twice with anhydrous ethanol, collect the load and vacuum dry it at 50° C. to obtain an α-cyclodextrin metal organic framework-sea buckthorn polyphenol complex.

[0043] Comparative Example 3 is an anhydrous ethanol solution of seabuckthorn polyphenols.

[0044] The above-mentioned Examples 1-2 and Comparative Examples 1-2 were subjected to performance tests under the following test conditions: 1) Appearance: Scanning electron microscopy (SEM) was used to observe the morphology, structure and surface characteristics of the delivery system.

[0045] 2) In vitro simulated gastrointestinal digestion test: Through the INFOGEST 2.0 digestion model, the simulated delivery system is digested in the mouth, stomach and intestines in turn, and then the simulated digestion of the delivery system in the gastrointestinal tract is evaluated.

[0046] Oral cavity: Mix the sample solution with simulated saliva to obtain a mixture; Gastric phase: simulated gastric fluid is added to the above oral mixture to obtain food gruel with a highly acidic pH, the food gruel is incubated at a simulated body temperature of 37°C, and then the pH value is adjusted to neutral to terminate gastric digestion; Intestinal phase: the above stop solution is mixed and incubated with simulated intestinal fluid to obtain a total digestive fluid, which is centrifuged under certain conditions to obtain a mixed micellar phase from the total digestive fluid, and finally processed through a 0.45 μm filter to quantitatively detect seabuckthorn polyphenols.

[0047] Bioaccessibility = concentration of seabuckthorn polyphenols in the system / concentration of seabuckthorn polyphenols in the total digestive juice × 100%.

[0048] Table 1 In vitro simulated gastrointestinal digestion

[0049] Depend on Figure 1 As shown in Figure 2, pure γ-CD-MOFs present a standard cubic structure. Figure 2 As shown, the delivery system of Example 1 still maintains the cubic structure of γ-CD-MOFs, and white granular substances remain on the surface, which may be residual seabuckthorn polyphenols. Figure 3 As shown, the delivery system of Example 2 has an incomplete shape and an irregular surface, but still maintains the cubic structure of γ-CD-MOFs. The CS-γ-CD-MOFs of Examples 1-2 have a stable structure and can effectively deliver seabuckthorn polyphenols to the colon.

[0050] As can be seen from Table 1, compared with the delivery system of Comparative Example 1 without chitosan coating, the delivery system of Comparative Example 2 using α-CD-MOFs and the seabuckthorn polyphenol solution of Comparative Example 3, the CS-γ-CD-MOFs delivery system of Example 1-2 has higher bioaccessibility, can effectively resist gastrointestinal digestion, and improves the bioavailability of seabuckthorn polyphenols.

[0051] The above examples are only used to further illustrate the technical content of the present invention, so that readers can understand it more easily, but it does not mean that the implementation of the present invention is limited to this. Any technical extension or re-creation made according to the present invention is protected by the present invention. The protection scope of the present invention shall be subject to the claims.

Claims

1. Chitosan-coated γ-cyclodextrin metal organic framework delivery system, characterized in that: The chitosan-coated cyclodextrin metal organic framework delivery system comprises a cyclodextrin metal organic framework used as a carrier, sea buckthorn polyphenol loaded on the cyclodextrin metal organic framework, and chitosan coating the cyclodextrin metal organic framework and the sea buckthorn polyphenol.

2. The chitosan-coated cyclodextrin metal organic framework delivery system according to claim 1, characterized in that: The preparation method of the cyclodextrin metal organic framework comprises the following steps: S11, dissolving: adding cyclodextrin and alkali metal cations to deionized water in proportion, dissolving with the aid of ultrasound to obtain a mixed stock solution; S12, filtration: filtering the mixed stock solution in step S11 using an organic filter membrane to obtain a filtrate; S13, diffusion crystallization: the filtrate in step S12 is transferred to a small container, and the small container is placed in a sealed container filled with methanol at room temperature for natural diffusion and crystallization to obtain crude crystals; S14, impurity removal: collecting the crude crystals described in step S13, washing the crude crystals with methanol, and then immersing them with dichloromethane to obtain pure crystals; S15, drying: placing the pure crystals in step S14 in a vacuum drying oven for drying to obtain a cyclodextrin metal organic framework.

3. The chitosan-coated cyclodextrin metal organic framework delivery system according to claim 2, characterized in that: In step S11, the cyclodextrin is γ-cyclodextrin, and the alkali metal cation is potassium ion.

4. The method for preparing the chitosan-coated γ-cyclodextrin metal organic framework delivery system according to claims 1-3, characterized in that: The following steps are involved: S1. Loading: uniformly mixing the cyclodextrin metal organic framework and the anhydrous ethanol solution of seabuckthorn polyphenol to obtain a mixed solution, and subjecting the mixed solution to ultrasonic treatment; S2, centrifugal collection: centrifuging the mixed solution treated with ultrasound in step S1, discarding the supernatant to obtain a load, washing the load with anhydrous ethanol, collecting the load and vacuum drying to obtain a cyclodextrin metal organic framework-sea buckthorn polyphenol complex; S3, coating: gradually adding the cyclodextrin metal organic framework-sea buckthorn polyphenol complex described in step S2 to the chitosan acetic acid solution to obtain a mixture, subjecting the mixture to ultrasonic treatment, using the mixture as an aqueous phase, and keeping it warm for later use; S4, emulsification and dispersion: under low-speed stirring, slowly drip the water phase in step S3 into the oil phase using a syringe, and after the water phase is dripped, stir and emulsify to obtain an emulsion; S5, cross-linking: adding a cross-linking agent to the emulsion in step S4 for cross-linking and curing. After the curing is completed, centrifugation is performed and the supernatant is discarded to obtain coarse microspheres; S6, washing and drying: the crude microspheres described in step S5 are repeatedly washed with petroleum ether, isopropanol and ultrapure water, respectively, filtered and vacuum dried to obtain a chitosan-coated γ-cyclodextrin metal organic framework delivery system.

5. The method for preparing the chitosan-coated γ-cyclodextrin metal organic framework delivery system according to claim 4, characterized in that: The preparation method of the anhydrous ethanol solution of seabuckthorn polyphenols in step S1 is as follows: adding seabuckthorn polyphenols into a 2 mg / ml ethanol solution and fully dissolving the seabuckthorn polyphenols.

6. The method for preparing the chitosan-coated γ-cyclodextrin metal organic framework delivery system according to claim 4, characterized in that: The insulation temperature of the water phase in step S3 and the oil phase in step S4 is 40°C.

7. The method for preparing the chitosan-coated γ-cyclodextrin metal organic framework delivery system according to claim 4, characterized in that: The oil phase in step S4 is liquid paraffin containing Span-80.

8. The method for preparing the chitosan-coated γ-cyclodextrin metal organic framework delivery system according to claim 4, characterized in that: In step S5, the cross-linking agent is glutaraldehyde, and the concentration of the glutaraldehyde is 50%.

9. The method for preparing the chitosan-coated γ-cyclodextrin metal organic framework delivery system according to claim 4, characterized in that: The cross-linking and curing time in step S5 is 2-2.5 hours.

10. Use of the chitosan-coated cyclodextrin metal organic framework delivery system according to claims 1-3 in the treatment of colon inflammation.

Images