Preparation method of a temperature-sensitive cyclodextrin metal-organic framework carrier carrying nutrient factors

Abstract

The present invention belongs to the technical field of biomaterials and provides a method for preparing a temperature-sensitive cyclodextrin metal-organic framework carrier carrying a nutrient factor. The method comprises the following steps: dissolving cyclodextrin in an alkali metal ion solution, filtering the solution through an organic filter membrane and placing the solution in a closed system filled with methanol, adding a poor solvent to allow the solution to stand to promote crystal formation, and obtaining the cyclodextrin metal-organic framework after centrifugal separation, washing, and drying; impregnating the nutrient factor into the cyclodextrin metal-organic framework to obtain a cyclodextrin metal-organic framework carrying the nutrient factor; and dispersing the cyclodextrin metal-organic framework carrying the nutrient factor into a composite solution of a temperature-sensitive polymer and soybean seed coat polysaccharide, slowly stirring, washing, and drying to obtain the temperature-sensitive cyclodextrin metal-organic framework carrier carrying the nutrient factor, which can enhance the hydrophilicity of the nutrient factor.

Description

Technical Field

[0001] The present invention relates to the technical field of biofunctional material preparation, and in particular to a method for preparing a nutrient factor-carrying temperature-sensitive cyclodextrin metal organic framework carrier. Background Art

[0002] Nutritional factors have multiple biological activities, and various delivery systems have been developed to package, protect, and release them. However, some nutritional factors face challenges such as strong hydrophobicity, susceptibility to oxidation, poor stability, and low oral bioavailability, which hinder their application.

[0003] The hydrophilicity of the carrier prepared by the related technology is poor. Therefore, there is an urgent need to develop a carrier with enhanced hydrophilicity of nutritional factors. Summary of the Invention

[0004] The purpose of the present invention is to provide a method for preparing a temperature-sensitive cyclodextrin metal organic framework carrier carrying a nutritional factor, so as to solve the problem of poor hydrophilicity of the nutritional factors in the prior art.

[0005] According to a first aspect of the present invention, a method for preparing a temperature-sensitive cyclodextrin metal-organic framework carrier loaded with a nutrient factor is provided, comprising the following steps: dissolving cyclodextrin in an alkali metal ion solution, filtering through an organic filter membrane and placing it in a closed system filled with methanol, adding a poor solvent to stand to promote crystal formation, and obtaining a cyclodextrin metal-organic framework after centrifugal separation, washing, and drying; impregnating the nutrient factor into the cyclodextrin metal-organic framework to obtain a cyclodextrin metal-organic framework loaded with the nutrient factor; dispersing the cyclodextrin metal-organic framework loaded with the nutrient factor into a composite solution of a temperature-sensitive polymer and soybean seed coat polysaccharide, slowly stirring, washing, and drying to obtain a temperature-sensitive cyclodextrin metal-organic framework carrier loaded with the nutrient factor.

[0006] Furthermore, the cyclodextrin is selected from at least one of α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin; and the nutritional factor is curcumin, lycopene or resveratrol.

[0007] Furthermore, the cyclodextrin is dissolved in an alkali metal ion solution by a vapor diffusion method, a hydrothermal method, a solvothermal method, a microwave-assisted method or a seed growth method.

[0008] Furthermore, the alkali metal ion solution is potassium hydroxide solution, sodium hydroxide solution or rubidium hydroxide solution.

[0009] Furthermore, the poor solvent is methanol, ethanol, acetone or chloroform.

[0010] Furthermore, the temperature-sensitive polymer is N-isopropylacrylamide, N-acryloylasparagine, N-acryloylglycineamide or N-acryloylglutamine.

[0011] Furthermore, the alkali metal ion solution is 1 mmol to 8 mmol; the molar ratio of cyclodextrin to alkali metal ion solution is 1:6 to 1:10; the poor solvent is 50 mL to 100 mL; and the organic filter membrane is selected to be 0.2 μm to 0.8 μm.

[0012] Furthermore, when the nutritional factors are impregnated into the cyclodextrin metal organic framework, the impregnation is carried out at 25° C. to 55° C. for 6 h to 48 h, and the mass ratio of the cyclodextrin metal organic framework to the nutritional factors is 1:1 to 1:5.

[0013] Furthermore, the concentration of the temperature-sensitive polymer is 10-30 mg / mL; the concentration of soybean seed coat polysaccharide is 0.05-1 wt %; and the mass ratio of the temperature-sensitive polymer to soybean seed coat polysaccharide is 1:5-1:10.

[0014] According to the second aspect of the present invention, a nutrient factor-loaded temperature-sensitive cyclodextrin metal-organic framework carrier is provided, and the nutrient factor-loaded temperature-sensitive cyclodextrin metal-organic framework carrier is prepared using the above-mentioned preparation method of the nutrient factor-loaded temperature-sensitive cyclodextrin metal-organic framework carrier.

[0015] Experimental verification shows that the nutrient factor-loaded temperature-sensitive cyclodextrin metal-organic framework carrier obtained by the preparation method of the nutrient factor-loaded temperature-sensitive cyclodextrin metal-organic framework carrier provided by the present invention can enhance the hydrophilicity of the nutrient factor.

[0016] Based on the implementation methods provided in the above aspects, this application can also be further combined to provide more implementation methods. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0018] Figure 1 Schematic diagram of the curcumin-loaded temperature-sensitive cyclodextrin metal-organic framework carrier of the present invention;

[0019] Figure 2 is the water contact angle of the support;

[0020] Figure 3 The loading capacity of curcumin at different temperatures (A), different times (B), and different mass ratios of curcumin to cyclodextrin metal-organic frameworks (C); LC (%) is the encapsulation efficiency of Cur; EE (%) is the amount of Cur loaded;

[0021] Figure 4 is the Fourier infrared transform spectrum of the material;

[0022] Figure 5 is the X-ray diffraction spectrum of the material;

[0023] Figure 6 TG curve of the material's thermogravimetric change;

[0024] Figure 7 DTA curve of the thermogravimetric change of the material;

[0025] Figure 8 The release curves of curcumin under different temperature conditions. DETAILED DESCRIPTION

[0026] In order to enable those skilled in the art to better understand the solutions of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work should fall within the scope of protection of the present invention. Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art.

[0027] The present invention provides a method for preparing a temperature-sensitive cyclodextrin metal-organic framework carrier loaded with nutrient factors, comprising the following steps: dissolving cyclodextrin in an alkali metal ion solution, filtering through an organic filter membrane and placing it in a closed system filled with methanol, adding a poor solvent to allow it to stand to promote crystal formation, centrifuging, washing, and drying to obtain a cyclodextrin metal-organic framework; impregnating the nutrient factor into the cyclodextrin metal-organic framework to obtain a cyclodextrin metal-organic framework loaded with the nutrient factor; dispersing the cyclodextrin metal-organic framework loaded with the nutrient factor into a composite solution of a temperature-sensitive polymer and soybean seed coat polysaccharide, slowly stirring, washing, and drying to obtain a temperature-sensitive cyclodextrin metal-organic framework carrier loaded with the nutrient factor. The method for preparing the temperature-sensitive cyclodextrin metal-organic framework carrier loaded with the nutrient factor provided by the present invention has simple steps, and the prepared temperature-sensitive cyclodextrin metal-organic framework carrier loaded with the nutrient factor can enhance the hydrophilicity of the nutrient factor.

[0028] Among them, metal-organic frameworks (MOFs) are porous crystalline materials formed by the self-assembly of metal ions or ion clusters with organic ligands. As functional molecular materials, they have rich topological structures, controllable sizes, adjustable pore sizes, large specific surface areas, and are easy to adsorb, embed, and functionalize. They have a wide range of applications in gas adsorption and storage, chemical sensing, catalysis, separation, and drug delivery. The functionalization of MOFs allows them to be modified with soft materials such as polymers to form flexible composite materials. Coating MOFs with smart, sensitive polymers not only protects the material but also enables intelligent responsive release, improving the bioavailability of bioactive substances. Soybean seed coat polysaccharides have excellent biocompatibility, high biodegradability, high permeability, hydrophilicity, and specific biological activities. The polysaccharide structure chain contains a large number of free hydroxyl, carboxyl, amino, and sulfate groups. These functional groups provide ample sites for chemical modification, showing great application potential in the preparation of functional factor delivery systems. Soybean seed coat polysaccharide is stable under acidic conditions and unstable under alkaline conditions. Therefore, when carrying drugs and food functional factors, it remains stable in the gastric environment and can be released in the intestine.

[0029] In this application, a cyclodextrin metal-organic framework loaded with nutritional factors is dispersed into a composite solution of a temperature-sensitive polymer and soybean seed coat polysaccharide, so that the temperature-sensitive polymer is grafted onto the surface of the cyclodextrin metal-organic framework loaded with nutritional factors. When the temperature is higher than the lower critical transition temperature, the molecular chain of the temperature-sensitive polymer shrinks, squeezing out the nutritional factors, thereby promoting the release of the nutritional factors. As the temperature changes, targeted release can be achieved.

[0030] Optionally, the cyclodextrin is selected from at least one of α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin.

[0031] Preferably, the cyclodextrin is γ-cyclodextrin. After ingestion, α-cyclodextrin and β-cyclodextrin are largely resistant to hydrolysis by α-amylase and have low absorption rates in the gastrointestinal tract. In contrast, γ-cyclodextrin is more readily hydrolyzed and utilized by digestive enzymes such as salivary amylase and pancreatic amylase. Furthermore, compared to α-cyclodextrin and β-cyclodextrin, γ-cyclodextrin is more hydrophobic, has the best water solubility, and is more bioavailable, leading to increasing demand in industries such as food, biopharmaceuticals, and daily chemicals.

[0032] Optionally, the nutritional factor is curcumin, lycopene or resveratrol.

[0033] Alternatively, the cyclodextrin is dissolved in an alkali metal ion solution by vapor diffusion, hydrothermal, solvothermal, microwave-assisted, or seeded growth methods.

[0034] Preferably, the cyclodextrin is dissolved in the alkali metal ion solution by the vapor diffusion method. The vapor diffusion method is a typical method for preparing cyclodextrin metal organic frameworks, which can obtain crystals with good properties and the reaction is easy to control.

[0035] Alternatively, the alkali metal ion solution is a potassium hydroxide solution, a sodium hydroxide solution or a rubidium hydroxide solution.The strong metal-ligand coordination bond produces a cyclodextrin metal-organic framework with high chemical and thermal stability.

[0036] Optionally, the poor solvent is methanol, ethanol, acetone or chloroform. The cyclodextrin metal organic framework has a certain morphological stability in organic solvents such as methanol, ethanol, acetone or chloroform.

[0037] Optionally, the temperature-sensitive polymer is N-isopropylacrylamide, N-acryloylasparagine, N-acryloylglycineamide or N-acryloylglutamine.

[0038] Preferably, the temperature-sensitive polymer is N-isopropylacrylamide. The molecular chain of N-isopropylacrylamide contains both a hydrophobic isopropyl group and a hydrophilic amide group. Changes in temperature will lead to changes in the interaction between the groups.

[0039] Optionally, the alkali metal ion solution is 1 mmol to 8 mmol. Alkali metal ions can generate sufficient alkalinity in aqueous solution to deprotonate the hydroxyl groups in γ-cyclodextrin and promote the growth rate of crystals. If the alkali metal ion concentration is too low, the crystal growth rate will be slow, and if the alkali metal ion concentration is too high, it will lead to larger crystals and too large crystal size. Experimental verification shows that when the amount of alkali metal ion solution added is within the above numerical range, the alkali metal ion concentration is within an appropriate range, which can ensure that the crystal growth rate is within a reasonable range and the crystal size is within an appropriate range.

[0040] Optionally, the molar ratio of cyclodextrin to alkali metal ion solution is 1:6 to 1:10. Adjusting the molar ratio of cyclodextrin to alkali metal ion solution can adjust the size of the cyclodextrin metal-organic framework. A high ratio results in overly large crystals, while a low ratio prevents crystal formation. Experimental results show that when the molar ratio of cyclodextrin to alkali metal ion solution is within this range, crystals can be formed while maintaining a reasonable size.

[0041] Optionally, the poor solvent is 50 mL to 100 mL. Poor solvents promote crystal formation; too low a concentration slows crystal growth, while too high a concentration results in unnecessary waste of the poor solvent. Experimental results show that when the amount of poor solvent added is within the above range, it can maintain a high crystal growth rate while avoiding unnecessary waste.

[0042] Optionally, the organic filter membrane is selected to be 0.2μm to 0.8μm. If the organic filter membrane is too small, cyclodextrin and alkali metal ions cannot pass through the membrane, and most substances cannot participate in the reaction. However, if the organic filter membrane is too high, large particles of substances can pass through, which in turn affects the size of the crystals. Experimental verification shows that when the organic filter membrane size is within the above numerical range, it can ensure that cyclodextrin and alkali metal ions can pass through the aluminum membrane while preventing unnecessary large particles from passing through, which is conducive to ensuring that the crystal size is within a reasonable range.

[0043] Optionally, the nutrient factor is impregnated into the cyclodextrin metal-organic framework at a temperature between 25°C and 55°C. The reaction temperature affects the encapsulation of the nutrient factor. As the temperature increases, molecular motion intensifies, promoting the binding of the nutrient factor to the cyclodextrin metal-organic framework. However, excessively high temperatures can hinder complex formation, as the binding of the nutrient factor to the porous material is an exothermic process. Experimental studies have shown that a reaction temperature within this range promotes both the binding of the nutrient factor to the cyclodextrin metal-organic framework and the formation of the complex.

[0044] Optionally, the nutrient factors are impregnated into the cyclodextrin metal-organic framework for 6 to 48 hours. If the impregnation time is too short, the nutrient factors are not fully incorporated into the cyclodextrin metal-organic framework. If the impregnation time is too long, some of the nutrient factors that have been impregnated into the cyclodextrin metal-organic framework may be lost. Experimental studies have shown that when the impregnation time is within the above range, the nutrient factors can be fully incorporated into the cyclodextrin metal-organic framework.

[0045] Optionally, when impregnating the nutrient factor into the cyclodextrin metal-organic framework, the mass ratio of the cyclodextrin metal-organic framework to the nutrient factor is 1:1 to 1:5. If the mass ratio of the cyclodextrin metal-organic framework to the nutrient factor is too low, the nutrient factor cannot be completely encapsulated within the cyclodextrin metal-organic framework. If the mass ratio is too high, some excess space will remain. Experimental verification has shown that when the mass ratio of the cyclodextrin metal-organic framework to the nutrient factor is within the above range, the nutrient factor can be completely encapsulated within the cyclodextrin metal-organic framework.

[0046] Preferably, it has been verified experimentally that the loading effect of the cyclodextrin metal organic framework on the nutritional factor is best when the cyclodextrin metal organic framework is immersed for 24 hours at a mass ratio of 1:3 to the nutritional factor.

[0047] Optionally, the concentration of the temperature-sensitive polymer is 10 to 30 mg / mL. If the concentration is too low, the surface of the cyclodextrin metal-organic framework will not be fully covered, affecting the temperature-sensitive response characteristics. If the concentration is too high, the crystallization performance of the crystal will be affected. Experimental verification shows that a temperature-sensitive polymer concentration within the above range can ensure complete coverage of the cyclodextrin metal-organic framework surface while avoiding affecting the crystallization performance of the crystal.

[0048] Optionally, the soybean seed coat polysaccharide concentration is 0.05-1 wt %. A low concentration of soybean seed coat polysaccharide can affect the surface coating, while a high concentration can cause severe particle agglomeration, as soybean seed coat polysaccharide is a macromolecule. Experimental studies have shown that a soybean seed coat polysaccharide concentration within this range can avoid affecting the surface coating, prevent severe particle agglomeration, and achieve intestinal release.

[0049] Optionally, the mass ratio of the temperature-sensitive polymer to soybean seed coat polysaccharide is 1:5 to 1:10. A too low mass ratio of the temperature-sensitive polymer to soybean seed coat polysaccharide concentration leads to particle agglomeration, while a too high mass ratio results in incomplete cross-linking of the soybean seed coat polysaccharide. Experimental results have shown that a mass ratio of the temperature-sensitive polymer to soybean seed coat polysaccharide within this range can prevent particle agglomeration and ensure complete cross-linking of the soybean seed coat polysaccharide.

[0050] The present invention also provides a temperature-sensitive cyclodextrin metal-organic framework carrier loaded with nutrient factors. The temperature-sensitive cyclodextrin metal-organic framework carrier loaded with nutrient factors is prepared using the above-mentioned preparation method of the temperature-sensitive cyclodextrin metal-organic framework carrier, which can enhance the hydrophilicity of the nutrient factors.

[0051] like Figure 1 As shown, taking curcumin (Cur) as an example, the present invention proposes a method for preparing a curcumin-loaded temperature-sensitive cyclodextrin metal-organic framework carrier, comprising the following steps:

[0052] (1) Dissolve γ-cyclodextrin (γ-CD) in alkali metal (K +) ion solution, and filtered through an organic filter membrane and placed in a closed system filled with methanol (mathauol), and then a poor solvent was added to promote crystal formation, centrifuged, washed, and dried to obtain cyclodextrin metal organic framework crystals (γ-CD-MOF); (2) Curcumin (Cur) was loaded into the cyclodextrin metal organic framework (γ-CD-MOF) to obtain a cyclodextrin metal organic framework loaded with curcumin (γ-CD-MOF-Cur); (3) Then, a mixed solution of N-isopropylacrylamide (PNIPAm) and soybean seed coat polysaccharide (SHP) was introduced on the basis of the cyclodextrin metal organic framework, and the mixture was prepared by cross-linking and reaction solvent precipitation to obtain a temperature-sensitive cyclodextrin metal organic framework carrier loaded with curcumin (γ-CD-MOF-PNIPAm@SHP). This renewable composite material shows potential advantages in the fields of food, environmental protection and pharmaceutical formulation. In addition, due to the safety, biodegradability and easy availability of raw materials, it is low in price and easy to commercialize.

[0053] In an embodiment of the present invention not shown in the figure, Figure 1 The curcumin (Cur) in the formula can be replaced with lycopene or resveratrol.

[0054] The specific embodiments of the present invention are described in detail below:

[0055] Example 1

[0056] Control group: Preparation of curcumin-loaded temperature-sensitive cyclodextrin metal-organic framework carrier.

[0057] (1) γ-cyclodextrin (γ-CD) and potassium hydroxide were mixed in a 10 mL beaker at a ratio of 1:8 mmol to obtain a colorless, transparent solution. The solution was filtered through a 0.45 μm organic filter membrane into another beaker containing 1 mL of methanol. The solution was then placed in a large beaker containing 120 mL of methanol and sealed with plastic wrap. The sealed large beaker was placed in a 50°C water bath and allowed to stand for 12 h. The solution was then removed and an equal volume of methanol solution was added to the mother liquor. The solution was allowed to stand overnight to promote crystallization. White needle-shaped crystals were produced in the solution. Finally, the precipitate was washed three times with methanol and freeze-dried in a vacuum oven to obtain γ-CD-MOF.

[0058] (2) Cur was impregnated into the γ-CD-MOF obtained in step (1), 10 mg of Cur was dissolved in 10 mL of anhydrous ethanol to prepare a 1% Cur solution, and then 30 mg of γ-CD-MOF was added. The mixture was slowly stirred at 35 ° C for 24 h to prepare a curcumin-loaded cyclodextrin metal organic framework (γ-CD-MOF-Cur).

[0059] (3) 10 mg / mL PNIPAm was dissolved in 0.5 wt% SHP solution, and then 30 mg γ-CD-MOF-Cur was dispersed in the composite solution of PNIPAm and SHP and slowly stirred, washed, and dried.

[0060] Example 2

[0061] Preparation of curcumin-loaded temperature-sensitive cyclodextrin metal-organic framework carrier.

[0062] (1) γ-CD and potassium hydroxide were mixed in a 10 mL beaker at a ratio of 1:8 mmol to obtain a colorless, transparent solution. The solution was filtered through a 0.45 μm organic filter membrane into another beaker containing 1 mL of methanol. The solution was then placed in a large beaker containing 120 mL of methanol and sealed with plastic wrap. The sealed large beaker was placed in a 50°C water bath and allowed to stand for 12 h. The solution was then removed and an equal volume of methanol solution was added to the mother liquor. The solution was allowed to stand overnight to promote crystallization. White needle-shaped crystals were produced in the solution. Finally, the precipitate was washed three times with methanol and freeze-dried in a vacuum oven to obtain γ-CD-MOF.

[0063] (2) Cur was impregnated into the γ-CD-MOF obtained in step (1). 10 mg of Cur was dissolved in 10 mL of anhydrous ethanol to prepare a 1% Cur solution. 30 mg of γ-CD-MOF was then added and slowly stirred at 25°C for 24 h to prepare γ-CD-MOF-Cur.

[0064] (3) 20 mg / mL PNIPAm was dissolved in 0.5 wt% SHP solution, and then 30 mg γ-CD-MOF-Cur was dispersed in the composite solution of PNIPAm and SHP and slowly stirred, washed, and dried.

[0065] Example 3

[0066] Preparation of curcumin-loaded temperature-sensitive cyclodextrin metal-organic framework carrier.

[0067] (1) γ-CD and potassium hydroxide were mixed in a 10 mL beaker at a ratio of 1:8 mmol to obtain a colorless, transparent solution. The solution was filtered through a 0.45 μm organic filter membrane into another beaker containing 1 mL of methanol. The solution was then placed in a large beaker containing 120 mL of methanol and sealed with plastic wrap. The sealed large beaker was placed in a 50°C water bath and allowed to stand for 12 h. The solution was then removed and an equal volume of methanol solution was added to the mother liquor. The solution was allowed to stand overnight to promote crystallization. White needle-shaped crystals were produced in the solution. Finally, the precipitate was washed three times with methanol and freeze-dried in a vacuum oven to obtain γ-CD-MOF.

[0068] (2) Cur was impregnated into the γ-CD-MOF obtained in step (1). 10 mg of Cur was dissolved in 10 mL of anhydrous ethanol to prepare a 1% Cur solution. 30 mg of γ-CD-MOF was then added and slowly stirred at 55 °C for 24 h to prepare γ-CD-MOF-Cur.

[0069] (3) 30 mg / mL PNIPAm was dissolved in 0.5 wt% SHP solution, and then 30 mg γ-CD-MOF-Cur was dispersed in the composite solution of PNIPAm and SHP and slowly stirred, washed, and dried.

[0070] Example 4

[0071] Preparation of curcumin-loaded temperature-sensitive cyclodextrin metal-organic framework carrier.

[0072] (1) γ-CD and potassium hydroxide were mixed in a 10 mL beaker at a ratio of 1:8 mmol to obtain a colorless, transparent solution. The solution was filtered through a 0.45 μm organic filter membrane into another beaker containing 1 mL of methanol. The solution was then placed in a large beaker containing 120 mL of methanol and sealed with plastic wrap. The sealed large beaker was placed in a 50°C water bath and allowed to stand for 12 h. The solution was then removed and an equal volume of methanol solution was added to the mother liquor. The solution was allowed to stand overnight to promote crystallization. White needle-shaped crystals were produced in the solution. Finally, the precipitate was washed three times with methanol and freeze-dried in a vacuum oven to obtain γ-CD-MOF.

[0073] (2) Cur was impregnated into the γ-CD-MOF obtained in step (1). 10 mg of Cur was dissolved in 10 mL of anhydrous ethanol to prepare a 1% Cur solution. 10 mg of γ-CD-MOF was then added and slowly stirred at 35 °C for 6 h to prepare γ-CD-MOF-Cur.

[0074] (3) 10 mg / mL PNIPAm was dissolved in 0.05 wt% SHP solution, and then 30 mg γ-CD-MOF-Cur was dispersed in the composite solution of PNIPAm and SHP and slowly stirred, washed, and dried.

[0075] Example 5

[0076] Preparation of curcumin-loaded temperature-sensitive cyclodextrin metal-organic framework carrier.

[0077] (1) γ-CD and potassium hydroxide were mixed in a 10 mL beaker at a ratio of 1:8 mmol to obtain a colorless, transparent solution. The solution was filtered through a 0.45 μm organic filter membrane into another beaker containing 1 mL of methanol. The solution was then placed in a large beaker containing 120 mL of methanol and sealed with plastic wrap. The sealed large beaker was placed in a 50°C water bath and allowed to stand for 12 h. The solution was then removed and an equal volume of methanol solution was added to the mother liquor. The solution was allowed to stand overnight to promote crystallization. White needle-shaped crystals were produced in the solution. Finally, the precipitate was washed three times with methanol and freeze-dried in a vacuum oven to obtain γ-CD-MOF.

[0078] (2) Cur was impregnated into the γ-CD-MOF obtained in step (1). 10 mg of Cur was dissolved in 10 mL of anhydrous ethanol to prepare a 1% Cur solution. 20 mg of γ-CD-MOF was then added and the mixture was slowly stirred at 35 °C for 12 h to prepare γ-CD-MOF-Cur.

[0079] (3) 10 mg / mL PNIPAm was dissolved in 0.1 wt% SHP solution, and then 30 mg γ-CD-MOF-Cur was dispersed in the composite solution of PNIPAm and SHP and slowly stirred, washed, and dried.

[0080] Example 6

[0081] (1) γ-CD and potassium hydroxide were mixed in a 10 mL beaker at a ratio of 1:8 mmol to obtain a colorless, transparent solution. The solution was filtered through a 0.45 μm organic filter membrane into another beaker containing 1 mL of methanol. The solution was then placed in a large beaker containing 120 mL of methanol and sealed with plastic wrap. The sealed large beaker was placed in a 50°C water bath and allowed to stand for 12 h. The solution was then removed and an equal volume of methanol solution was added to the mother liquor. The solution was allowed to stand overnight to promote crystallization. White needle-shaped crystals were produced in the solution. Finally, the precipitate was washed three times with methanol and freeze-dried in a vacuum oven to obtain γ-CD-MOF.

[0082] (2) Cur was impregnated into the γ-CD-MOF obtained in step (1). 10 mg of Cur was dissolved in 10 mL of anhydrous ethanol to prepare a 1% Cur solution. 40 mg of γ-CD-MOF was then added and slowly stirred at 35 °C for 36 h to prepare γ-CD-MOF-Cur.

[0083] (3) 10 mg / mL PNIPAm was dissolved in 1 wt% SHP solution, and then 30 mg γ-CD-MOF-Cur was dispersed in the composite solution of PNIPAm and SHP and slowly stirred, washed, and dried.

[0084] Example 7

[0085] (1) γ-CD and potassium hydroxide were mixed in a 10 mL beaker at a ratio of 1:8 mmol to obtain a colorless, transparent solution. The solution was filtered through a 0.45 μm organic filter membrane into another beaker containing 1 mL of methanol. The solution was then placed in a large beaker containing 120 mL of methanol and sealed with plastic wrap. The sealed large beaker was placed in a 50°C water bath and allowed to stand for 12 h. The solution was then removed and an equal volume of methanol solution was added to the mother liquor. The solution was allowed to stand overnight to promote crystallization. White needle-shaped crystals were produced in the solution. Finally, the precipitate was washed three times with methanol and freeze-dried in a vacuum oven to obtain γ-CD-MOF.

[0086] (2) Cur was impregnated into the γ-CD-MOF obtained in step (1). 10 mg of Cur was dissolved in 10 mL of anhydrous ethanol to prepare a 1% Cur solution. 50 mg of γ-CD-MOF was then added and slowly stirred at 35 °C for 48 h to prepare γ-CD-MOF-Cur.

[0087] (3) 10 mg / mL PNIPAm was dissolved in 0.5 wt% SHP solution, and then 30 mg γ-CD-MOF-Cur was dispersed in the composite solution of PNIPAm and SHP and slowly stirred, washed, and dried.

[0088] Example 8

[0089] Preparation of lycopene-loaded temperature-sensitive cyclodextrin metal-organic framework carrier.

[0090] (1) γ-CD and potassium hydroxide were mixed in a 10 mL beaker at a ratio of 1:8 mmol to obtain a colorless, transparent solution. The solution was filtered through a 0.45 μm organic filter membrane into another beaker containing 1 mL of methanol. The solution was then placed in a large beaker containing 120 mL of methanol and sealed with plastic wrap. The sealed large beaker was placed in a 50°C water bath and allowed to stand for 12 h. The solution was then removed and an equal volume of methanol solution was added to the mother liquor. The solution was allowed to stand overnight to promote crystallization. White needle-shaped crystals were produced in the solution. Finally, the precipitate was washed three times with methanol and freeze-dried in a vacuum oven to obtain γ-CD-MOF.

[0091] (2) Lycopene was impregnated into the γ-CD-MOF obtained in step (1). 10 mg of lycopene was dissolved in 10 mL of anhydrous ethanol to prepare a 1% lycopene solution. 10 mg of γ-CD-MOF was then added and slowly stirred at 35°C for 6 h to prepare a lycopene-loaded cyclodextrin metal-organic framework.

[0092] (3) 10 mg / mL PNIPAm was dissolved in 0.5 wt% SHP solution, and then 30 mg of lycopene-loaded cyclodextrin metal organic framework was dispersed in the composite solution of PNIPAm and SHP and slowly stirred, washed, and dried.

[0093] Example 9

[0094] Preparation of resveratrol-loaded temperature-sensitive cyclodextrin metal-organic framework carrier.

[0095] (1) γ-CD and potassium hydroxide were mixed in a 10 mL beaker at a ratio of 1:8 mmol to obtain a colorless, transparent solution. The solution was filtered through a 0.45 μm organic filter membrane into another beaker containing 1 mL of methanol. The solution was then placed in a large beaker containing 120 mL of methanol and sealed with plastic wrap. The sealed large beaker was placed in a 50°C water bath and allowed to stand for 12 h. The solution was then removed and an equal volume of methanol solution was added to the mother liquor. The solution was allowed to stand overnight to promote crystallization. White needle-shaped crystals were produced in the solution. Finally, the precipitate was washed three times with methanol and freeze-dried in a vacuum oven to obtain γ-CD-MOF.

[0096] (2) Resveratrol was impregnated into the γ-CD-MOF obtained in step (1), 10 mg of resveratrol was dissolved in 10 mL of anhydrous ethanol to prepare a 1% resveratrol solution, and then 50 mg of γ-CD-MOF was added. The mixture was slowly stirred at 35°C for 48 hours to prepare a cyclodextrin metal organic framework loaded with resveratrol.

[0097] (3) 10 mg / mL PNIPAm was dissolved in 0.5 wt% SHP solution, and then 30 mg of resveratrol-loaded cyclodextrin metal organic framework was dispersed in the composite solution of PNIPAm and SHP and slowly stirred, washed, and dried.

[0098] Depend on Figure 2 The water contact angle of the γ-CD-MOF-Cur composite is significantly lower than that of Cur. The smaller the contact angle, the easier it is for the release medium to wet the carrier surface, leading to carrier disintegration and subsequent release of curcumin. This suggests that loading Cur with γ-CD-MOF significantly improves its hydrophilicity. The γ-CD-MOF-Cur-PNIPAm@SHP composite has the lowest water contact angle (15.5°). This is due to the hydrophilic phthalamide (-CONH-) groups on the PNIPAm macromolecular side chains. Furthermore, SHP contains a large number of -OH and -COOH groups, which promote interaction or coordination with curcumin.

[0099] By comparing Example 1, Example 2, and Example 3, the loading capacity of γ-CD-MOF-Cur prepared at different temperatures for curcumin was obtained. Figure 3 As shown in A.

[0100] Depend on Figure 3 A shows that at 35 °C, the prepared γ-CD-MOF-Cur has the best loading effect on curcumin.

[0101] By comparing Example 1, Example 4, Example 5, Example 6, and Example 7, the loading capacity of γ-CD-MOF-Cur prepared at different mass ratios of Cur and γ-CD-MOF was obtained, as shown in FIG. Figure 3 As shown in C.

[0102] Depend on Figure 3 Taking into account the encapsulation efficiency LC (%) and drug loading EE (%) of Cur in C, when the mass ratio of Cur to γ-CD-MOF carrier is 1:3, the prepared γ-CD-MOF-Cur has the best loading effect on curcumin.

[0103] Comparing Example 2, Example 4, Example 5, Example 6, and Example 7, the loading capacity of γ-CD-MOF-Cur prepared at different times for curcumin was obtained. Figure 3 As shown in B.

[0104] Depend on Figure 3 B shows that when immersed for 24 h, the prepared γ-CD-MOF-Cur has the best loading effect on curcumin.

[0105] Depend on Figure 4 The Fourier transform infrared spectra of γ-CD-MOF, γ-CD-MOF-Cur and γ-CD-MOF-Cur-PNIPAm@SHP are shown in (1020-1150cm -1 ) has a subtle broad absorption peak, which comes from the stretching vibration of COC. The γ-CD-MOF-Cur spectrum shows that some of the Cur peaks disappear, indicating that Cur is successfully encapsulated in the carrier. The stretching vibration peak of OH in γ-CD-MOF (3394cm -1 ) and γ-CD-MOF-Cur(3373cm -1 ), indicating that the hydrogen bond in γ-CD-MOF-Cur is stronger and hydrogen bond is the main driving force for the combination of Cur and γ-CD-MOF. In the spectrum of γ-CD-MOF-Cur-PNIPAm@SHP, the hydrogen bond in γ-CD-MOF-Cur is stronger at 1347 cm -1 and 1593cm -1 There is a peak at 1740-1630cm -1) is sharper, indicating that PNIPAm and SHP are successfully cross-linked to the surface of γ-CD-MOF-Cur.

[0106] like Figure 5 As shown in Figure 3, powder XRD shows that surface grafting of PNIPAm and SHP does not introduce phase changes and still retains the crystal structure of γ-CD-MOF.

[0107] like Figure 6 As shown, the thermogravimetric data show that, except for Cur, the thermogravimetric curves in the embodiments are close to each other, indicating that the surface grafting of PNIPAm and SHP does not cause the loss of the thermal stability of γ-CD-MOF, thus ensuring the thermal stability of the material.

[0108] like Figure 7 As shown in the figure, from the analysis of the thermogravimetric change DTA curve, it can be seen that the thermal decomposition temperature of the surface grafted PNIPAm and SHP is lower than the thermal decomposition temperature of γ-CD-MOF, which further shows that the surface grafting of PNIPAm and SHP does not cause the loss of the thermal stability of γ-CD-MOF, thus ensuring the thermal stability of the material.

[0109] Figure 8 Figure 3 is the release curve of curcumin in γ-CD-MOF-PNIPAm@SHP at different temperatures. The release at different temperatures is different. There is a significant difference in the release of curcumin below the lower critical transition temperature (LCST) and above the lower critical transition temperature, which proves the controllability of curcumin release.

[0110] Specifically, if Figure 8As shown, Cur release from γ-CD-MOF-Cur-PNIPAm@SHP at different temperatures shows low Cur release at 25°C, while higher release rates are observed at 37°C and 45°C. This is due to the expansion of the grafted PNIPAm at temperatures below the liquid crystal standstill (LCST) (32°C). In this state, the pores of the γ-CD-MOF-Cur-PNIPAm@SHP are covered by the expanded PNIPAm, resulting in slow Cur release. Conversely, at temperatures above the LCST, the grafted PNIPAm shrinks. This contraction of PNIPAm opens the pores of the SHP, reducing the capacity of the γ-CD-MOF-Cur-PNIPAm@SHP and accelerating Cur release. The combined release of Cur shows slight variations between 37°C and 45°C, likely due to the sample reaching sufficient contraction conditions. Therefore, targeted release can be effectively controlled with temperature fluctuations. These results demonstrate that the PNIPAm chains attached to the pore surface effectively act as a thermosensitive valve for Cur release. The temperature-dependent “on / off” behavior of γ-CD-MOF-Cur-PNIPAm@SHP facilitates the regulated release of the functional agent by simply changing the surrounding temperature, which allows the reversible release of the functional agent by temperature changes.

[0111] In the related art, there is research on enhancing the bioavailability of curcumin by embedding curcumin with cyclodextrin to generate cyclodextrin-curcumin inclusion complex. For example, the patent application document with publication number CN104873983A discloses a curcumin cyclodextrin inclusion complex and its preparation method. However, due to the poor stability of curcumin under alkaline conditions, it needs to be adjusted to neutrality in time with hydrochloric acid after inclusion, and the process is relatively cumbersome. The patent application document with publication number CN112870371A discloses the application of cyclodextrin-metal organic framework in the preparation of inhalants. Inhalants can achieve good drug lung delivery efficiency, but their application range is small and the effect cannot meet actual needs. U.S. published patent application 20060067998 describes a colloidal drug delivery system for parenteral administration of curcumin. The inventor discloses a liposome drug delivery system and polymer-based nanoparticles and micron particles. Generally, water-insoluble drugs like curcumin are incorporated into the lipid membrane of the liposome rather than the aqueous phase inside the liposome, which can limit the amount of incorporated drugs and their stability. None of the above related technologies discloses the preparation method of the present invention and the curcumin-loaded temperature-sensitive cyclodextrin metal-organic framework carrier prepared by the present invention that can enhance the hydrophilicity of curcumin.

[0112] The beneficial technical effects of the present invention are:

[0113] The preparation method of the temperature-sensitive cyclodextrin metal organic framework carrier loaded with nutrient factors and the prepared temperature-sensitive cyclodextrin metal organic framework carrier loaded with nutrient factors provided by the present invention enhance the hydrophilicity of the nutrient factors and make the release rate more controllable.

[0114] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included in the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. A method for preparing a temperature-sensitive cyclodextrin metal organic framework carrier loaded with nutrient factors, characterized in that: The following steps are involved: The cyclodextrin is dissolved in an alkali metal ion solution, filtered through an organic filter membrane, placed in a closed system filled with methanol, a poor solvent is added to promote crystal formation, and the cyclodextrin metal organic framework is obtained after centrifugal separation, washing, and drying. impregnating the nutritional factors into the cyclodextrin metal-organic framework to obtain a cyclodextrin metal-organic framework loaded with the nutritional factors; Dispersing the cyclodextrin metal organic framework loaded with nutritional factors into a composite solution of a temperature-sensitive polymer and soybean seed coat polysaccharide, slowly stirring, washing, and drying to obtain a nutrient factor-loaded temperature-sensitive cyclodextrin metal organic framework carrier; Wherein, the temperature-sensitive polymer is N-isopropylacrylamide, and the temperature-sensitive polymer is grafted onto the surface of the cyclodextrin metal-organic framework loaded with nutritional factors; When the nutritional factors are impregnated into the cyclodextrin metal organic framework, the immersion temperature is 25°C to 55°C for 6 h to 48 h, and the mass ratio of the cyclodextrin metal organic framework to the nutritional factors is 1:1 to 1:5; The concentration of the temperature-sensitive polymer is 10-30 mg / mL; The concentration of the soybean seed coat polysaccharide is 0.05-1 wt %; The mass ratio of the temperature-sensitive polymer to soybean seed coat polysaccharide is 1:5 to 1:

10.

2. The method for preparing the temperature-sensitive cyclodextrin metal organic framework carrier loaded with nutrient factors according to claim 1, characterized in that: The cyclodextrin is selected from at least one of α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin; The nutritional factor is curcumin, lycopene or resveratrol.

3. The method for preparing the temperature-sensitive cyclodextrin metal organic framework carrier loaded with nutrient factors according to claim 1, characterized in that: The cyclodextrin is dissolved in an alkali metal ion solution by a vapor diffusion method, a hydrothermal method, a solvothermal method, a microwave-assisted method or a seed growth method.

4. The method for preparing the temperature-sensitive cyclodextrin metal organic framework carrier loaded with nutrient factors according to claim 1, characterized in that: The alkali metal ion solution is potassium hydroxide solution, sodium hydroxide solution or rubidium hydroxide solution.

5. The method for preparing the temperature-sensitive cyclodextrin metal organic framework carrier loaded with nutrient factors according to claim 1, characterized in that: The poor solvent is methanol, ethanol, acetone or chloroform.

6. The method for preparing the temperature-sensitive cyclodextrin metal organic framework carrier loaded with nutrient factors according to claim 1, characterized in that: The alkali metal ion solution is 1 mmol to 8 mmol; The molar ratio of the cyclodextrin to the alkali metal ion solution is 1:6 to 1:10; The poor solvent is 50 mL to 100 mL; The organic filter membrane is selected to be 0.2µm~0.8µm.

7. A temperature-sensitive cyclodextrin metal organic framework carrier loaded with nutritional factors, characterized in that: The nutrient factor-loaded temperature-sensitive cyclodextrin metal-organic framework carrier is prepared using the preparation method of the nutrient factor-loaded temperature-sensitive cyclodextrin metal-organic framework carrier according to any one of claims 1 to 6.

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