CN107151328B

CN107151328B - Sucralose-loaded cyclodextrin-metal organic framework compound and preparation method thereof

Info

Publication number: CN107151328B
Application number: CN201610125454.0A
Authority: CN
Inventors: 张继稳; 吕娜娜; 王彩芬; 伍丽; 郭桢
Original assignee: Shanghai Institute of Materia Medica of CAS
Current assignee: Shanghai Institute of Materia Medica of CAS
Priority date: 2016-03-04
Filing date: 2016-03-04
Publication date: 2020-11-06
Anticipated expiration: 2036-03-04
Also published as: CN107151328A

Abstract

The invention relates to a sucralose-loaded cyclodextrin-metal organic framework compound and a preparation method thereof. Specifically, the method takes cyclodextrin-metal organic framework materials (CD-MOFs) as carriers, sucralose is loaded, the CD-MOF compound carrying sucralose is prepared, and the loading efficiency and the thermal stability of sucralose are improved by controlling the feeding ratio of the CD-MOFs to sucralose and carrying out acidification treatment on the CD-MOFs. The CD-MOF compound carrying the sucralose can obviously improve the thermal stability of the sucralose, and the method is quick, simple, convenient, high in yield, safe, cheap and easily available in used raw materials and solvents, and beneficial to industrial production.

Description

Sucralose-loaded cyclodextrin-metal organic framework compound and preparation method thereof

Technical Field

The invention relates to the field of biological materials, and in particular relates to a sucralose-loaded cyclodextrin-metal organic framework compound and a preparation method thereof.

Background

The cyclodextrin-metal organic framework mainly utilizes the fact that cyclodextrin can form a new crystal with first and second main group metal ions in an organic coordination mode in an aqueous solution, and the crystal has the characteristics of being porous, large in surface area, capable of storing gas and the like. The green and porous material can adsorb some medicine with unstable structure, and its huge cavity can protect medicine, so that it can be used for commercial development, in particular, the cyclodextrin-metal organic skeleton is edible derivative, and is suitable for human being. The cyclodextrin is taken as an organic ligand, and the metal ion is taken as an inorganic metal center, so that a novel cyclodextrin-metal organic framework which has higher safety and is used for medicine, namely CD-MOFs, can be formed.

Sucralose (Sucralose) is a novel sweetener developed by telai corporation of great britain (Tate & Lyle) together with university of london and patented in 1976. The non-nutritive intense sweetener is prepared by chlorination of sucrose serving as a raw material, has the sweetness of 400-800 times that of the sucrose, has the characteristics of no energy, high sweetness, pure sweetness, high safety and the like, and is one of the most excellent functional sweeteners at present. Sucralose is very soluble in water, ethanol and methanol, is slightly soluble in ethyl acetate, and is stable to light, heat and pH value changes. In aqueous solution, the sucralose is the most stable in nature of all strong sweeteners in the pH range (pH 3-5) of soft drinks and at normal temperature, and can be stored for more than one year without any change in nature. However, sucralose crystals have poor stability under high-temperature drying conditions and are prone to color change, for example, sucralose changes from colorless to grayish brown within 2min at a temperature of 100 ℃. In order to ensure the quality of the product, the thermal stability of sucralose must be improved. Cherukuri et al, 1990, have proposed a method of including sucralose with a cyclodextrin to prepare a co-crystal of sucralose and cyclodextrin to improve the thermal stability of sucralose. However, the preparation of the inclusion compound is complicated, organic solvents such as methanol and ethyl acetate are required, and the stability of sucralose is not significantly improved.

In view of the foregoing, there is a strong need in the art to develop materials and methods for improving the stability of sucralose.

Disclosure of Invention

The invention aims to provide a sucralose-loaded cyclodextrin-metal organic framework compound and a preparation method thereof.

In a first aspect of the present invention, there is provided a method of preparing a sucralose-loaded cyclodextrin-metal-organic framework complex, comprising the steps of:

(I) providing a cyclodextrin-metal organic framework material;

(II) adding the cyclodextrin-metal organic framework material into an organic solvent A containing sucralose, and performing shaking incubation treatment to obtain a sucralose-loaded cyclodextrin-metal organic framework compound,

the feeding mol of the cyclodextrin-metal organic framework material and the sucralose is 1 (1-10), preferably 1 (3-8), more preferably 1 (5-7), wherein the molar amount of the cyclodextrin-metal organic framework material is calculated according to the molar amount of the cyclodextrin; and

(III) optionally separating and/or drying the sucralose-loaded cyclodextrin-metal-organic framework complex precipitated in step (II).

In another preferred embodiment, the sucralose-loaded cyclodextrin-metal-organic framework complex has one or more characteristics selected from the group consisting of:

(1) the thermal decomposition temperature of the sucralose in the compound is 200-500 ℃, preferably 210-300 ℃;

(2) heat treatment is carried out for 24 hours at the temperature of 90 ℃, and the degradation of the sucralose in the compound is less than or equal to 60 percent, preferably less than or equal to 20 percent, and more preferably less than or equal to 5 percent;

(3) the molar ratio of cyclodextrin to sucralose in the complex is 1 (0.3-2), preferably 1 (0.5-1.8), more preferably 1 (0.8-1.5);

(4) the content (w/w) of the sucralose in the compound is more than or equal to 5 percent, preferably more than or equal to 15 percent, and more preferably more than or equal to 25 percent;

(5) the thermal decomposition temperature of the sucralose in the compound is increased by more than or equal to 80 ℃, preferably by more than or equal to 88 ℃ compared with the thermal decomposition temperature of the free sucralose.

In another preferred embodiment, the cyclodextrin-metal-organic framework material comprises a nanoscale cyclodextrin-metal-organic framework material and a microscale cyclodextrin-metal-organic framework material.

In a further preferred embodiment, the cyclodextrin-metal-organic framework material comprises an acidified cyclodextrin-metal-organic framework material and/or a basic cyclodextrin-metal-organic framework material.

In another preferred embodiment, the cyclodextrin-metal-organic framework material is an acidified nanoscale cyclodextrin-metal-organic framework material.

In another preferred embodiment, the basic cyclodextrin-metal-organic framework material has the following characteristics: when the basic cyclodextrin-metal organic framework material is dissolved in water to prepare 10mg/mL aqueous solution, the pH value of the aqueous solution is 11-13.

In another preferred embodiment, the acidified cyclodextrin-metal-organic framework material has the following characteristics: when the acidified cyclodextrin-metal organic framework material is dissolved in water to prepare a 10mg/mL aqueous solution, the pH of the aqueous solution is 5-8, preferably 5.5-7.5.

In another preferred example, the basic cyclodextrin-metal-organic framework material is subjected to an acidification treatment, thereby obtaining the acidified cyclodextrin-metal-organic framework material.

In another preferred example, the acidification treatment comprises the steps of:

adding the cyclodextrin-metal organic framework material into an acid-containing organic solvent B, and performing shaking incubation treatment to obtain the acidified cyclodextrin-metal organic framework material.

In another preferred embodiment, in the acidification treatment, the time of the shaking incubation treatment is 0.5-6h, preferably 1-2 h.

In another preferred example, the acidification treatment further comprises a step of separating and/or drying the obtained acidified cyclodextrin-metal organic framework material.

In another preferred embodiment, the acid is an organic acid or an inorganic acid.

In another preferred embodiment, the organic acid is selected from the group consisting of: glacial acetic acid, formic acid, citric acid, fumaric acid, tartaric acid, malic acid, or adipic acid, or combinations thereof.

In another preferred embodiment, the organic acid is selected from the group consisting of: formic acid, acetic acid, or a combination thereof.

In another preferred embodiment, the volume ratio of the organic acid to the organic solvent B is 1 (5-20), preferably 1 (10-15).

In another preferred embodiment, the inorganic acid is selected from the group consisting of: hydrochloric acid, phosphoric acid, sulfuric acid, or a combination thereof.

In another preferred embodiment, the organic solvent a and the organic solvent B are each independently selected from the group consisting of: methanol, ethanol, isopropanol, acetone, acetonitrile

In another preferred example, the organic solvent a and the organic solvent B are ethanol.

In another preferred embodiment, the temperature of the shaking incubation treatment is 25-45 ℃, preferably 30-42 ℃.

In another preferred embodiment, the rotation speed of the shaking incubation treatment is 80-200rpm, preferably 100-150 rpm.

In another preferred embodiment, in step (II), the treatment time of the shaking incubation treatment is 12-72h, preferably 18-48h, more preferably 20-24 h.

In another preferred embodiment, in step (I), the method further comprises the step of preparing the basic cyclodextrin-metal organic framework material:

(1) providing a first mixed solution, wherein the first mixed solution is a solution containing metal ions and cyclodextrin;

(2) adding a first organic solvent into the first mixed solution to obtain a second mixed solution,

wherein the volume ratio of the first organic solvent to the first mixed solution is (0.01-5):1, preferably (0.1-2):1, and most preferably (0.5-1): 1;

(3) pretreating the second mixed solution to obtain a pretreated first mixture, wherein the pretreatment is selected from the group consisting of: solvothermal treatment, microwave treatment, ultrasonic treatment, or a combination thereof;

(4) optionally, when the precipitated basic cyclodextrin-metal organic framework material is contained in the first mixture, separating the precipitated basic cyclodextrin-metal organic framework material from the first mixture;

(5) when a part or all of the solution is separated from the first mixture, the solution is used as a third mixed solution; adding a second organic solvent and/or a size regulator into the third mixed solution, so as to precipitate the alkaline cyclodextrin-metal organic framework material; and

(6) optionally separating and/or drying the basic cyclodextrin-metal-organic framework material precipitated in step (5).

In another preferred embodiment, the total time T of step (3) and step (5) is 0.1 to 24 hours, preferably 0.2 to 12 hours, more preferably 0.5 to 6 hours, and most preferably 0.5 to 3 hours (e.g., about 1 hour).

In another preferred embodiment, the first organic solvent and the second organic solvent are each independently selected from the group consisting of: methanol, ethanol, isopropanol, acetone, acetonitrile, or combinations thereof.

In another preferred embodiment, the first organic solvent and the second organic solvent are the same or different.

In another preferred embodiment, the first organic solvent and the second organic solvent are methanol.

In another preferred embodiment, the step (4) may or may not be performed.

In another preferred embodiment, the prepared basic cyclodextrin-metal-organic framework material has one or more characteristics selected from the group consisting of:

(i) average particle size: 50nm-50 μm, preferably 100 nm-1000 nm (nanometer scale) or 1-10 μm (micrometer scale)

(ii) In the basic cyclodextrin-metal organic framework material, the molar ratio of CD to metal ions is 1: 8;

(iii) the alkaline cyclodextrin-metal organic framework material is a pharmaceutically acceptable carrier;

(iv) the alkaline cyclodextrin-metal organic framework material can have a good protection effect on heat-labile drugs.

In another preferred embodiment, the temperature of the pretreatment is 25 to 100 ℃, preferably 30 to 80 ℃, more preferably 40 to 60 ℃.

In another preferred embodiment, the time of the pretreatment is 10min to 24h, preferably 15min to 1h, and more preferably 20 to 30 min.

In another preferred embodiment, the solvent heat treatment is water bath heating or oil bath heating of the mixed solution.

In another preferred embodiment, the power of the microwave treatment is 20-1000W, preferably 25-100W.

In another preferred embodiment, the radiation frequency of the microwave treatment is 916-2450MHz, preferably 2450 MHz.

In another preferred embodiment, the power of the ultrasonic treatment is 20-1000W, preferably 40W.

In another preferred embodiment, the radiation frequency of the ultrasonic treatment is 22-100KHz, preferably 30-50 KHz.

In another preferred embodiment, in step (5), the volume ratio of the second organic solvent to the third mixed solution is (0.01-5):1, preferably (0.5-2):1, and more preferably 1:1.

In another preferred embodiment, the third mixed solution is a supernatant.

In another preferred embodiment, in step (5), the size-regulating agent is added in an amount of 1-20mg/mL, preferably 5-10 mg/mL.

In another preferred example, in the step (5), the first mixture is centrifuged to separate a part of the solution from the first mixture.

In another preferred embodiment, the rotation speed of the centrifugal treatment is 1000-5000rpm, preferably 2000-3000 rpm.

In another preferred embodiment, the time for the centrifugation treatment is 3-10min, preferably 5-8 min.

In another preferred example, in the step (6), the method comprises the steps of:

(a) centrifuging the pretreated mixed solution to never obtain a precipitate;

(b) washing the precipitate; and

(c) and (3) drying the washed precipitate in vacuum to obtain the crystallized basic cyclodextrin-metal organic framework material.

In another preferred example, in step (b), the precipitate is washed with ethanol.

In another preferred embodiment, in step (c), the temperature of the vacuum drying is 40-60 ℃.

In another preferred embodiment, in step (c), the vacuum drying time is 6-24 h.

In another preferred example, in the step (1), an aqueous solution of the metal compound and an aqueous solution of cyclodextrin are mixed to obtain the first mixed solution.

In another preferred example, in the step (1), the metal compound and the cyclodextrin are dissolved in water, thereby obtaining the first mixed solution.

In another preferred embodiment, the metal compound comprises a metal salt and a metal base.

In another preferred embodiment, the metal compound is KOH.

In another preferred embodiment, the concentration of the metal ions in the first mixed solution is 0.05-0.4M, preferably 0.1-0.3M, and more preferably 0.2M.

In another preferred embodiment, the concentration of cyclodextrin in the first mixed solution is 0.013-0.05M, preferably 0.02-0.03M, more preferably 0.025M.

In another preferred embodiment, the molar ratio of cyclodextrin to metal ion in the first mixed solution is 1: (6-10), preferably 1: 8.

In another preferred embodiment, the metal ion is selected from the group consisting of: li⁺、K⁺、Rb⁺、Cs⁺、Na⁺、Mg²⁺、Cd²⁺、 Sn²⁺、Ag⁺、Yb⁺、Ba²⁺、Sr²⁺、Ca²⁺、Pb²⁺、La³⁺Or a combination thereof.

In another preferred embodiment, the metal ion is K⁺。

In another preferred embodiment, the cyclodextrin is selected from the group consisting of: alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, hydroxypropyl-beta-cyclodextrin, sulfobutyl-beta-cyclodextrin, methyl-beta-cyclodextrin, carboxymethyl-beta-cyclodextrin, or a combination thereof.

In another preferred embodiment, the cyclodextrin is gamma-cyclodextrin.

In another preferred embodiment, the size-adjusting agent comprises polyethylene glycol, povidone, polysorbate, sorbitan monolaurate, polyoxyethylene lauryl ether, emulsifier OP (nonylphenol polyoxyethylene ether condensate), lacto-butrin a (polyoxyethylene fatty alcohol ether), pluronic (polyoxyethylene polypropylene glycol condensate), sodium lauryl sulfate, sodium dodecylbenzenesulfonate, dodecyldimethylbenzyl ammonium bromide (benzalkonium bromide), or a combination thereof.

In another preferred embodiment, the polyethylene glycol comprises PEG200, PEG400, PEG600, PEG800, PEG1000, PEG1500, PEG2000, PEG4000, PEG6000, PEG8000, PEG10000, PEG20000, or a combination thereof.

In another preferred example, the povidone comprises PVP K12, PVP K15, PVP K17, PVP K25, PVPK30, PVP K60, PVP K90, PVP K120, or a combination thereof.

In another preferred embodiment, the polysorbate comprises tween 20, tween 40, tween 60, tween 80, tween 85, or a combination thereof.

In another preferred embodiment, the sorbitan monolaurate comprises span 20, span 40, span 60, span 80, or a combination thereof.

In another preferred embodiment, the size-adjusting agent comprises PEG2000, PEG4000, PEG6000, PEG8000, PEG10000, PEG20000, or a combination thereof, preferably PEG 20000.

(1') providing a first mixed solution, wherein the first mixed solution is a solution containing metal ions and cyclodextrin;

(2') adding a first organic solvent to said first mixed solution to obtain a second mixed solution,

wherein the volume ratio of the first organic solvent to the first mixed solution is (0.01-0.5):1, preferably (0.03-0.3):1, and most preferably (0.05-0.2): 1;

(3') pretreating said second mixed solution to obtain a pretreated first mixture, wherein said pretreatment is selected from the group consisting of:

(a) carrying out solvent thermal volatilization treatment;

(b) a combination of solvothermal volatilization treatment with any one of the treatment modalities selected from group a, wherein group a comprises solvothermal treatment, microwave treatment, ultrasonication, or a combination thereof;

(4') when the first mixture contains precipitated basic cyclodextrin-metal organic framework material, separating the precipitated basic cyclodextrin-metal organic framework material from the first mixture;

or separating part or all of the solution from the first mixture to serve as a third mixed solution; adding a second organic solvent and/or a size regulator into the third mixed solution, so as to precipitate the alkaline cyclodextrin-metal organic framework material; and

(5') optionally separating and/or drying the basic cyclodextrin-metal-organic framework material precipitated in step (4').

In another preferred embodiment, in step (3'), the solvent thermal volatilization treatment comprises the steps of:

(a') placing the mixed solution in an open container I;

(b') providing an open container II containing an organic solvent, and placing the open container I and the open container II together in a closed system; and

(c') heating/maintaining the temperature of the organic solvent in the open container II so that the organic solvent is evaporated and diffused into the mixed solution.

In another preferred example, in the step (c'), the closed system is subjected to an overall heating treatment to heat the organic solvent in the open vessel II

In another preferred example, in step (c'), the heating treatment includes water bath heating, and oil bath heating.

In another preferred embodiment, in step (c'), the temperature of the heat treatment is 25 to 100 ℃, preferably 30 to 80 ℃, more preferably 40 to 60 ℃.

In another preferred embodiment, in step (c'), the time of the heat treatment is 4 to 48 hours, preferably 6 to 24 hours.

In a second aspect of the invention, there is provided a complex comprising (a) a cyclodextrin-metal organic framework material; and (b) sucralose supported on the framework material.

In a third aspect of the invention, there is provided a sucralose-loaded cyclodextrin-metal-organic framework complex prepared by the method of the first aspect of the invention.

Preferably, the composite of the second or third aspect of the invention further has one or more features selected from the group consisting of:

(5) the thermal decomposition temperature of the sucralose in the compound is increased by more than or equal to 80 ℃ (such as 80-100 ℃) compared with the thermal decomposition temperature of the free sucralose, and the thermal decomposition temperature of the sucralose in the compound is preferably increased by more than or equal to 88 ℃.

The invention prepares the cyclodextrin-metal organic framework based on cyclodextrin and alkali metal and alkaline earth metal by using a rapid and simple method, and prepares the micron-scale and nano-scale cyclodextrin-metal organic framework materials by adding a crystal size regulator. Dispersing the obtained cyclodextrin-metal organic framework into an organic solvent containing organic acid, incubating for a certain time, and collecting solid to obtain acidified cyclodextrin-metal organic framework (neutral cyclodextrin-metal organic framework material); preparing a sucralose solution by using an organic solvent, placing a cyclodextrin-metal organic framework or a neutral cyclodextrin metal organic framework in the sucralose organic solution, incubating for a certain time at a certain temperature, collecting solids, and drying to obtain the sucralose-loaded cyclodextrin-metal organic framework.

The methods described herein include methods for rapidly preparing micro-and nano-sized cyclodextrin-metal organic frameworks. The preparation method of the micron-sized cyclodextrin-metal organic framework comprises the following steps: preparing metal salt and cyclodextrin water solution, adding a part of organic solvent in advance, reacting for a period of time by a solvothermal volatilization method, taking supernatant fluid, adding a size regulator, and then separating out a cyclodextrin-metal organic framework; the nanometer level cyclodextrin-metal organic skeleton is prepared through compounding metal salt and cyclodextrin aqua, adding partial organic solvent, thermal volatilizing to obtain supernatant, adding partial organic solvent, adding size regulator and separating out cyclodextrin-metal organic skeleton. Or mixing a metal salt solution and a cyclodextrin aqueous solution, adding a part of organic solvent in advance, placing the mixture in a closed container, heating a reaction medium by using solvothermal/microwave/ultrasonic waves to enable reactants to react quickly, taking out supernatant after reacting for a certain time, and adding a size regulator to obtain the cyclodextrin-based metal organic framework material. In addition, the method also comprises the steps of centrifuging the reaction solution after the reaction is finished, collecting and washing the precipitate and drying in vacuum.

The method for preparing the neutral cyclodextrin-metal organic framework comprises the following steps: dispersing the obtained micron-sized cyclodextrin-metal organic framework or nano-sized cyclodextrin-metal organic framework into an organic solvent containing organic acid, incubating for a certain time, and collecting solids, namely the neutral micron-sized cyclodextrin-metal organic framework or the neutral nano-sized cyclodextrin-metal organic framework.

The method for incubating sucralose by using the cyclodextrin-metal organic framework comprises the following steps: preparing a sucralose solution by using an organic solvent, weighing a cyclodextrin-metal organic framework (micron-scale/nanometer-scale) or a neutral cyclodextrin-metal organic framework (micron-scale/nanometer-scale) according to a certain feeding ratio, placing the cyclodextrin-metal organic framework (micron-scale/nanometer-scale) or the neutral cyclodextrin-metal organic framework (micron-scale/nanometer-scale) in the sucralose solution, incubating for a certain time at a certain temperature, collecting a solid after the incubation is finished, and drying the obtained solid in vacuum.

The organic solvent used for preparing the neutral cyclodextrin-metal organic framework is methanol and ethanol. Ethanol is preferred.

When the sucralose-loaded cyclodextrin-metal organic framework is prepared, the feeding proportion of the cyclodextrin metal organic framework (micron-scale/nanometer-scale) or the neutral cyclodextrin-metal organic framework (micron-scale/nanometer-scale) and sucralose is 1mol:1 mol-7 mol.

When the sucralose-loaded cyclodextrin-metal organic framework is prepared, the incubation method is shaking incubation or stirring incubation. Preferably, the incubation is performed with shaking.

It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.

Drawings

FIG. 1 is an optical micrograph of CD-MOF I prepared by the solvent evaporation method in example 1.

FIG. 2 is an optical micrograph of CD-MOF II obtained by the solvent evaporation method in example 2.

FIG. 3 is a scanning electron micrograph of CD-MOF II obtained by the solvent evaporation method in example 2.

FIG. 4 is a scanning electron micrograph of CD-MOF Nano obtained by the solvent evaporation method in example 3.

FIG. 5 is an X-ray powder diffraction pattern of CD-MOF I obtained by the solvent evaporation method in example 1.

FIG. 6 is an X-ray powder diffraction pattern of CD-MOF II obtained by the solvent evaporation method in example 2.

FIG. 7 is an X-ray powder diffraction pattern of CD-MOF Nano obtained by the solvent evaporation method in example 3.

FIG. 8 is a graph showing the distribution of the particle size of CD-MOF II obtained by the solvent evaporation method in example 2.

FIG. 9 is an optical micrograph of CD-MOF II obtained by the solvothermal method in example 4.

FIG. 10 is an optical micrograph of CD-MOF II obtained by the solvothermal method in example 5.

FIG. 11 is an optical micrograph of CD-MOF II obtained by the solvothermal method in example 6.

FIG. 12 is an optical micrograph of CD-MOF II obtained by the solvothermal method in example 7.

FIG. 13 is a scanning electron micrograph of CD-MOF II obtained by the solvothermal method in example 4.

FIG. 14 is a scanning electron micrograph of CD-MOF Nano obtained by the solvothermal method in example 8.

FIG. 15 is an X-ray powder diffraction pattern of CD-MOF II obtained by the solvothermal method in example 4.

FIG. 16 is an X-ray powder diffraction pattern of CD-MOF Nano obtained by the solvothermal method in example 8.

FIG. 17 is a graph showing the distribution of the particle size of CD-MOF II obtained by the solvothermal method in example 4.

FIG. 18 is a graph showing the distribution of the particle size of CD-MOF II obtained by the solvothermal method in example 5.

FIG. 19 is a graph showing the distribution of the particle size of CD-MOF II obtained by the solvothermal method in example 6.

FIG. 20 is a graph showing the distribution of the particle size of CD-MOF II obtained by the solvothermal method in example 7.

FIG. 21 is an optical micrograph of CD-MOF II obtained by the microwave method in example 9.

FIG. 22 is a scanning electron micrograph of CD-MOF II obtained by the microwave method in example 9.

FIG. 23 is a scanning electron micrograph of the CD-MOF Nano obtained by the microwave method in example 10.

FIG. 24 is an X-ray powder diffraction pattern of CD-MOF II obtained by the microwave method in example 9.

FIG. 25 is an X-ray powder diffraction pattern of CD-MOF Nano obtained by the microwave method in example 10.

FIG. 26 is an optical micrograph of CD-MOF II obtained by ultrasonication in example 11.

FIG. 27 is a scanning electron micrograph of CD-MOF II obtained by the ultrasonication in example 11.

FIG. 28 is a scanning electron micrograph of a CD-MOF Nano obtained by the ultrasonication in example 12.

FIG. 29 is an X-ray powder diffraction pattern of CD-MOF II obtained by the ultrasonication in example 11.

FIG. 30 is an X-ray powder diffraction pattern of CD-MOF Nano obtained by the ultrasonication in example 12.

FIG. 31 is a graph of the degradation curves of sucralose and sucralose-loaded alkaline microscale CD-MOF complexes of example 13.

FIG. 32 is a graph of the degradation curves of sucralose and sucralose-loaded basic nanoscale CD-MOF complexes of example 14.

FIG. 33 shows the results of thermal analysis of sucralose.

FIG. 34 is the results of thermal analysis of sucralose-loaded basic nanoscale CD-MOF complexes from example 14.

FIG. 35 is a graph of the degradation curves of sucralose and sucralose-loaded neutral micrometer sized CD-MOF complexes from example 15.

FIG. 36 is a graph of the degradation curves of sucralose and sucralose-loaded neutral nanoscale CD-MOF complexes of example 16.

FIG. 37 is the results of thermal analysis of sucralose-loaded neutral nanoscale CD-MOF complexes from example 16.

FIG. 38 is an X-ray diffraction pattern of basic micro-scale CD-MOFs, basic nano-scale CD-MOFs, neutral micro-scale CD-MOFs, and neutral nano-scale CD-MOFs.

FIG. 39 is a scanning electron micrograph of basic micro-scale CD-MOFs, basic nano-scale CD-MOFs, neutral micro-scale CD-MOFs, and neutral nano-scale CD-MOFs.

FIG. 40 is a graph showing the degradation curves of sucralose and sucralose-loaded neutral nanoscale CD-MOF complexes of examples 16, 17, 18, 19, and 20, wherein the molar ratios of CD-MOF to sucralose as charged during the preparation of the complexes are 1:1, 1:3, 1:5, 1:7, and 1:28, respectively, as calculated from the ratio of cyclodextrin to sucralose.

FIG. 41 is a graph showing the degradation curves of sucralose and sucralose-loaded neutral micro-sized CD-MOF complexes of examples 15, 21, 22, and 23, wherein the molar ratios of CD-MOF to sucralose during the preparation of the complexes are respectively 1:1, 1:3, 1:5, and 1:7, calculated according to the ratio of cyclodextrin to sucralose.

FIG. 42 is a graph showing the degradation curves of sucralose and sucralose-loaded basic nanoscale CD-MOF complexes of examples 14, 24, 25, and 26, wherein the molar ratios of CD-MOF to sucralose during the preparation of the complexes are 1:1, 1:3, 1:5, and 1:7, respectively, as calculated from the ratio of cyclodextrin to sucralose.

FIG. 43 is a graph showing the degradation curves of sucralose and sucralose-loaded alkaline microscale CD-MOF complexes of examples 13, 27, 28, and 29, wherein the molar ratios of CD-MOF to sucralose during the preparation of the complexes are 1:1, 1:3, 1:5, and 1:7, respectively, as calculated from the ratio of cyclodextrin to sucralose.

FIG. 44 shows the thermal analysis results of sucralose/beta-cyclodextrin inclusion compound in example 30.

FIG. 45 shows the thermal analysis results of sucralose/γ -cyclodextrin inclusion compound of example 31.

FIG. 46 is a Thermogravimetric (TGA) curve of sucralose and sucralose-loaded basic nanoscale CD-MOF complexes, sucralose-loaded neutral nanoscale CD-MOF complexes, sucralose/β -cyclodextrin inclusion compounds, sucralose/γ -cyclodextrin inclusion compounds, and sucralose in examples 14, 16, 30, 31.

FIG. 47 is a Differential Scanning Calorimetry (DSC) curve for sucralose and sucralose-loaded basic nanoscale CD-MOF complexes, sucralose-loaded neutral nanoscale CD-MOF complexes, sucralose/β -cyclodextrin inclusion compounds, sucralose/γ -cyclodextrin inclusion compounds, and sucralose in examples 14, 16, 30, 31.

Detailed Description

The inventor of the present invention has extensively and deeply studied, and unexpectedly found a sucralose-loaded cyclodextrin-metal organic framework complex and a preparation method thereof for the first time. Specifically, the method takes cyclodextrin-metal organic framework materials (CD-MOFs) as carriers, sucralose is loaded, the CD-MOF compound carrying sucralose is prepared, and the loading efficiency and the thermal stability of sucralose are improved by controlling the feeding ratio of the CD-MOFs to sucralose and carrying out acidification treatment on the CD-MOFs. The CD-MOF compound carrying the sucralose can obviously improve the thermal stability of the sucralose, and the method is quick, simple, convenient, high in yield, safe, cheap and easily available in used raw materials and solvents, and beneficial to industrial production.

Sucralose

Sucralose (Sucralose) is a novel sweetener developed by telai corporation of great britain (Tate & Lyle) together with university of london and patented in 1976. The non-nutritive intense sweetener is prepared by chlorination of sucrose serving as a raw material, has the sweetness of 400-800 times that of the sucrose, has the characteristics of no energy, high sweetness, pure sweetness, high safety and the like, and is one of the most excellent functional sweeteners at present. Sucralose is very soluble in water, ethanol and methanol, is slightly soluble in ethyl acetate, and is stable to light, heat and pH value changes. In aqueous solution, the sucralose is the most stable in nature of all strong sweeteners in the pH range (pH 3-5) of soft drinks and at normal temperature, and can be stored for more than one year without any change in nature. However, sucralose crystals have poor stability under high-temperature drying conditions and are prone to color change, for example, sucralose changes from colorless to grayish brown within 2min at a temperature of 100 ℃.

Cyclodextrin-metal organic framework compound carrying sucralose

As used herein, the terms "sucralose-loaded cyclodextrin-metal organic framework complex", "sucralose-loaded cyclodextrin-metal organic framework", "sucralose-loaded CD-MOF complex", "sucralose-loaded CD-MOF", "CD-MOF-sucralose", all of which are used interchangeably, represent the sample resulting from the incubation of CD-MOF with a sucralose solution.

The cyclodextrin-metal organic framework compound carrying the sucralose can obviously improve the stability of the sucralose at high temperature, and the used raw materials and solvents are cheap and easy to obtain, thereby being beneficial to industrial production.

Cyclodextrin-metal organic framework material

As used herein, the terms "cyclodextrin-based metal-organic framework material", "cyclodextrin-metal-organic framework compound" are used interchangeably and utilize the ability of cyclodextrin to form a new crystal in an organic coordination with first and second main group metal ions in aqueous solution, such a crystal being porous, having a large surface area, and storing a gas. The green and porous material can adsorb some medicine with unstable structure, and its huge cavity can protect medicine, so that it can be used for commercial development, in particular, the cyclodextrin-metal organic skeleton is edible derivative, and is suitable for human being. The cyclodextrin is taken as an organic ligand, and the metal ion is taken as an inorganic metal center, so that a novel cyclodextrin-metal organic framework which has higher safety and is used for medicine, namely CD-MOFs, can be formed.

As used herein, the term "CD-MOF I" refers to first stage CD-MOF crystals, meaning that γ -CD is mixed with KOH and the resulting crystals are precipitated directly by evaporation from methanol vapor over time; the first stage CD-MOF crystals produced by the process of the invention are about 40 to 500 μm in size.

As used herein, the term "CD-MOF II" refers to second stage CD-MOF crystals, meaning that γ -CD is mixed with KOH, evaporated by methanol vapor, and when no or only a small amount of first stage crystals are produced, the supernatant is removed, size-adjusting agent is added, and then the resulting crystals are re-precipitated; the second stage CD-MOF crystals produced by the process of the invention are about 1-10 μm in size.

As used herein, the term "CD-MOF Nano" refers to Nano-sized CD-MOF crystals, meaning that γ -CD is mixed with KOH, evaporated by methanol vapor, and when no or only a small amount of first stage crystals are produced, the supernatant is taken out, a large amount of methanol is added according to the volume of the supernatant, a size-adjusting agent is added, and then the resulting crystals are separated out; the size of the CD-MOF Nano prepared by the method is about 200-500 nm.

As used herein, the term "basic cyclodextrin-metal organic framework material" refers to a cyclodextrin-metal organic framework material prepared from an alkali metal and cyclodextrin as starting materials, which is basic and has a pH of about 11 to 13 when dissolved in water to form a 10mg/mL aqueous solution.

As used herein, the terms "neutral cyclodextrin-metal organic framework material" and "acidified cyclodextrin-metal organic framework material" are used interchangeably and refer to a near neutral cyclodextrin-metal organic framework material obtained by acidifying a basic cyclodextrin-metal organic framework material, which has a pH of about 5 to about 8 when dissolved in water to form a 10mg/mL aqueous solution. One preferred method of acidification is as follows: weighing a certain amount of cyclodextrin-metal organic framework, placing in ethanol, adding a certain amount of glacial acetic acid, incubating at 25 deg.C under shaking for a certain time, and washing the obtained solid with ethanol to obtain near-neutral cyclodextrin-metal organic framework.

Metal organic framework material

Metal-organic frameworks (MOFs) are crystalline materials formed by connecting inorganic Metal centers by organic bridging ligands through coordination bonds. Due to the ultrahigh porosity and huge specific surface area of the MOFs and the structure consisting of different inorganic and organic components, the structure of the MOFs is diversified and adjustable, so that the MOFs have potential application values in various fields such as gas storage, catalysis, drug carriers and the like.

Cyclodextrin

Cyclodextrin is a generic name for a series of cyclic oligosaccharides produced from amylose by the action of glucosyltransferase, and generally contains 6 to 12D-glucopyranose units. Among them, the more studied and of great practical significance are molecules containing 6, 7, 8 glucose units, called α, β -and γ -cyclodextrins, respectively. Cyclodextrins are ideal host molecules found to date to resemble enzymes and have the properties of an enzyme model in their own right.

Pre-adding organic solvent

In the method, a certain amount of organic solvent is added in advance in a reaction system before the reaction, so that the obtained CD-MOFs crystals can be separated out more quickly, meanwhile, the excessive organic solvent cannot be added, otherwise, the dissolved cyclodextrin is easy to be directly separated out, and finally, the obtained CD-MOFs are doped with a part of cyclodextrin.

Pretreatment of

In the method of the present invention, for the purpose of achieving a rapid reaction, a mixed solution containing a metal salt and cyclodextrin, which is pre-added with an organic solvent, is subjected to a pretreatment including a solvothermal treatment, a microwave treatment, and/or an ultrasonic treatment.

The solvothermal method is the optimization of the hydrothermal method, microwave treatment can enable substance molecules to generate high-frequency vibration, so that heat is generated, the temperature is quickly raised, substance transfer is enhanced, reaction activation energy is reduced, the reaction between potassium hydroxide and gamma-cyclodextrin is promoted, heating is uniform, heat conduction time is shortened, and the defect of nonuniform heating in the traditional method is avoided. The ultrasonic treatment is mainly to utilize ultrasonic cavitation to enable the reaction solution to generate a series of actions such as expansion, compression, collapse and the like, and the generated chemical effect and mechanical effect can improve the reaction condition and accelerate the reaction speed. The generation and the closing of the microwave and the ultrasonic energy are instantaneous, have no thermal inertia, are safe and reliable, and are convenient for automatic control.

The main advantages of the invention include:

(a) the method is simple, convenient and quick, does not need large-scale equipment, does not have harsh conditions in the synthesis process, and saves energy.

(b) The cyclodextrin-based metal organic framework material prepared by the method has regular size and high yield.

(c) The method can avoid the waste of the organic solvent and reduce the damage to the environment.

(d) The cyclodextrin used in the invention is harmless to human body and is beneficial to industrial production and preparation.

(e) The ethanol used for incubating the sucralose by the cyclodextrin-metal organic framework is nontoxic and harmless to human bodies, and is suitable for industrial production.

(f) The method for incubating and carrying the sucralose by the cyclodextrin-metal organic framework is simple and convenient, and can be realized by simple shaking or stirring

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out under conventional conditions or conditions recommended by the manufacturers. Unless otherwise indicated, percentages and parts are by weight.

Example 1

Preparation of first-stage CD-MOF crystals by solvothermal volatilization method

163.0mg of γ -CD and 56.0mg of KOH mixture (molar ratio of γ -CD to KOH: 0.125) were dissolved in 5mL of water, sonicated for 10 minutes to allow sufficient dissolution, and filtered through a 0.45 μm filter. Then 0.5mL of methanol is added into the mixed solution of the gamma-CD and the KOH in advance, and the methanol is heated in a closed container at the temperature of 50 ℃ (the whole closed container is heated), so that the methanol steam is evaporated into the mixed system of the gamma-CD and the KOH. And (3) generating a small amount of crystals after reacting for 6 hours, obtaining a large amount of colorless transparent crystals after reacting for 24 hours, discarding supernatant, centrifuging for 5min at 3000rpm, washing with ethanol (10mL multiplied by 3), and vacuum-drying the obtained crystals for 12 hours at 50 ℃ to obtain the first-stage CD-MOF crystals (CD-MOF I) which can be stored for a long time, wherein the size of the first-stage CD-MOF crystals is 40-500 mu m, and the yield is 76.3% as shown in figures 1 and 5.

Example 2

Method for preparing second-stage micron-sized CD-MOF crystals by solvothermal volatilization method

163.0mg of γ -CD and 56.0mg of KOH mixture (molar ratio of γ -CD to KOH: 0.125) were weighed out and dissolved in 5mL of water, sonicated for 10 minutes to dissolve it thoroughly, and filtered through a 0.45 μm filter. Then 0.5mL of methanol is added into the mixed solution of the gamma-CD and the KOH in advance, and the methanol is heated in a closed container at the temperature of 50 ℃ (the whole closed container is heated), so that the methanol steam is evaporated into the mixed system of the gamma-CD and the KOH. After 6 hours of reaction, taking out the supernatant, adding PEG20000 according to the proportion of 8mg/mL of the supernatant, standing for half an hour, centrifuging for 5min at 3000rpm, respectively washing with ethanol (10mL multiplied by 2) and dichloromethane (10mL multiplied by 2), and vacuum drying the obtained crystals for 12 hours at 50 ℃ to obtain second-stage micron-sized CD-MOF crystals (CD-MOF II) which can be stored for a long time and have the size of 1-10 mu m, such as figure 2, figure 3, figure 6 and figure 8, wherein the yield is 85.1%.

Example 3

Method for preparing second-stage nanoscale CD-MOF crystals by solvothermal volatilization method

163.0mg of γ -CD and 56.0mg of KOH mixture (molar ratio of γ -CD to KOH: 0.125) were dissolved in 5mL of water, sonicated for 10 minutes to allow sufficient dissolution, and filtered through a 0.45 μm filter. Then 0.5mL of methanol is added into the mixed solution of the gamma-CD and the KOH in advance, and the methanol is heated in a closed container at the temperature of 50 ℃ (the whole closed container is heated), so that the methanol steam is evaporated into the mixed system of the gamma-CD and the KOH. After 6 hours of reaction, taking out the supernatant, adding methanol with the same volume, adding PEG20000 according to the proportion of 8mg/mL of the supernatant, standing for half an hour, centrifuging at 3000rpm for 5min, respectively washing with ethanol (10mL multiplied by 2) and dichloromethane (10mL multiplied by 2), and vacuum drying the obtained crystal for 1 hour at 50 ℃ to obtain the second-stage nanoscale CD-MOF crystal (CD-MOF Nano) with the size of 200 plus 500nm, as shown in figures 4 and 7, the yield is 90.3%.

Example 4

Solvothermal method for preparing second-stage micron-sized CD-MOF crystals

And directly heating a mixed system of the gamma-cyclodextrin, KOH aqueous solution and a part of organic solvent by using a solvothermal mode. Weighing 163.0mg of gamma-CD and 56.0mg of KOH mixture (the molar ratio of the gamma-CD to the KOH is 0.125) to be dissolved in 5mL of water, adding 3mL of methanol into the mixed solution in advance, heating in a water bath at 50 ℃ for 20min, taking out the solution, adding 64mg of PEG20000, standing for half an hour, centrifuging at 3000rpm for 5min, washing with ethanol (10mL multiplied by 2) and dichloromethane (10mL multiplied by 2) respectively, and drying the obtained crystals in vacuum at 50 ℃ for 12h to obtain second-stage micron-sized CD-MOF crystals (CD-MOF II) with the size of 1-10 mu m, as shown in the figure 9, the figure 13, the figure 15 and the figure 17, wherein the yield is 87.0%.

Example 5

Solvothermal method for preparing second-stage micron-sized CD-MOF crystals

And directly heating a mixed system of the gamma-cyclodextrin, KOH aqueous solution and a part of organic solvent by using a solvothermal mode. Weighing 163.0mg of gamma-CD and 56.0mg of KOH mixture (the molar ratio of the gamma-CD to the KOH is 0.125) to be dissolved in 5mL of water, adding 3mL of methanol into the mixed solution in advance, heating in a water bath at 50 ℃ for 20min, taking out the solution, adding 16mg of PEG20000, standing for half an hour, centrifuging at 3000rpm for 5min, washing with ethanol (10mL multiplied by 2) and dichloromethane (10mL multiplied by 2) respectively, and drying the obtained crystals in vacuum at 50 ℃ for 12h to obtain second-stage micron-sized CD-MOF crystals (CD-MOF II) with the size of 1-10 mu m, as shown in the graph 10 and the graph 18, wherein the yield is 58.3%.

Example 6

Solvothermal method for preparing second-stage micron-sized CD-MOF crystals

And directly heating a mixed system of the gamma-cyclodextrin, KOH aqueous solution and a part of organic solvent by using a solvothermal mode. Weighing 163.0mg of gamma-CD and 56.0mg of KOH mixture (the molar ratio of the gamma-CD to the KOH is 0.125), dissolving in 5mL of water, adding 3mL of methanol into the mixed solution, heating in a water bath at 50 ℃ for 20min, taking out the solution, adding 64mg of PEG2000, standing for half an hour, centrifuging at 3000rpm for 5min, washing with ethanol (10mL multiplied by 2) and dichloromethane (10mL multiplied by 2), respectively, and drying the obtained crystals in vacuum at 50 ℃ for 12h to obtain second-stage micron-sized CD-MOF crystals (CD-MOF II) with the size of 1-10 mu m, as shown in FIGS. 11 and 19, and the yield is 83.0%.

Example 7

Solvothermal method for preparing second-stage micron-sized CD-MOF crystals

And directly heating a mixed system of the gamma-cyclodextrin, KOH aqueous solution and a part of organic solvent by using a solvothermal mode. Weighing 163.0mg of gamma-CD and 56.0mg of KOH mixture (the molar ratio of the gamma-CD to the KOH is 0.125), dissolving in 5mL of water, adding 3mL of methanol into the mixed solution, heating in a water bath at 50 ℃ for 20min, taking out the solution, adding 64mg of PEG10000, standing for half an hour, centrifuging at 3000rpm for 5min, washing with ethanol (10mL multiplied by 2) and dichloromethane (10mL multiplied by 2), respectively, and drying the obtained crystals in vacuum at 50 ℃ for 12h to obtain second-stage micron-sized CD-MOF crystals (CD-MOF II) with the size of 1-10 mu m, as shown in figures 12 and 20, the yield is 87.4%.

Example 8

Solvothermal method for preparing second-stage nanoscale CD-MOF crystals

And directly heating a mixed system of the gamma-cyclodextrin, KOH aqueous solution and a part of organic solvent by using a solvothermal mode. 163.0mg of gamma-CD and 56.0mg of KOH mixture (the molar ratio of gamma-CD to KOH is 0.125) are weighed and dissolved in 5mL of water, 3mL of methanol is added into the mixed solution in advance, after the mixture is heated in a water bath at 50 ℃ for 20min, the solution is taken out, methanol with the same volume is added, 64mg of PEG20000 is added, after the mixture is kept still for half an hour, the mixture is centrifuged at 3000rpm for 5min, the mixture is respectively washed by ethanol (10mL multiplied by 2) and dichloromethane (10mL multiplied by 2), and the obtained crystals are dried in vacuum at 50 ℃ for 12h to obtain second-stage nano-scale CD-MOF crystals (CD-MOano), the size of which is 200 and 500nm, as shown in figures 14 and 16, the yield is 90.

Example 9

Microwave method for preparing second-stage micron-sized CD-MOF crystals

And (3) microwave heating is carried out on the mixed system of the gamma-cyclodextrin, KOH aqueous solution and a part of organic solvent by using a microwave mode. Weighing 163.0mg of gamma-CD and 56.0mg of KOH mixture (the molar ratio of the gamma-CD to the KOH is 0.125), dissolving in 5mL of water, adding 3mL of methanol into the mixed solution, setting the power of a microwave reactor at 2450MHz to 25W, setting the temperature to 50 ℃, reacting for 20min, taking out the solution, adding 64mg of PEG20000, standing for half an hour, centrifuging at 3000rpm for 5min, washing with ethanol (10mL multiplied by 2) and dichloromethane (10mL multiplied by 2), respectively, and vacuum-drying the obtained crystals at 50 ℃ for 12h to obtain second-stage micron-sized CD-MOF crystals (CD-MOF II) with the size of 1-10 mu m, as shown in figure 21, figure 22 and figure 24, wherein the yield is 82.2%.

Example 10

Preparation of second-stage nano-scale CD-MOF crystal by microwave method

And (3) microwave heating is carried out on the mixed system of the gamma-cyclodextrin, KOH aqueous solution and a part of organic solvent by using a microwave mode. 163.0mg of gamma-CD and 56.0mg of KOH mixture (the molar ratio of gamma-CD to KOH is 0.125) are weighed and dissolved in 5mL of water, 3mL of methanol is added into the mixed solution in advance, a microwave reactor with 2450MHz is used, the power is set to 25W, the temperature is set to 50 ℃, after 20min of reaction, the solution is taken out, methanol with the same volume is added, 64mg of PEG20000 is added, after standing for half an hour, the solution is centrifuged at 3000rpm for 5min, the solution is respectively washed by ethanol (10mL multiplied by 2) and dichloromethane (10mL multiplied by 2), and the obtained crystals are dried in vacuum at 50 ℃ for 12h to obtain second-stage nanoscale CD-MOF crystals (CD-MOF Nano), the size of which is 200-500nm, as shown in figures 23 and 25, the yield of 90.1%.

Example 11

Preparation of second-stage micron-sized CD-MOF crystals by ultrasonic method

And (3) ultrasonically heating a mixed system of the gamma-cyclodextrin, KOH aqueous solution and a part of organic solvent by using an ultrasonic mode. Weighing 163.0mg of gamma-CD and 56.0mg of KOH mixture (the molar ratio of the gamma-CD to the KOH is 0.125), dissolving in 5mL of water, adding 3mL of methanol into the mixed solution in advance, using a 40KHz ultrasonic reactor with the power set at 40W and the temperature of 50 ℃, taking out supernatant after 20min of reaction, adding 64mg of PEG20000, standing for half an hour, centrifuging for 5min at 3000rpm, washing with ethanol (10mL multiplied by 2) and dichloromethane (10mL multiplied by 2), respectively, and drying the obtained crystals in vacuum at 50 ℃ for 12h to obtain second-stage micron-sized CD-MOF crystals (CD-MOF II) with the size of 1-10 mu m, as shown in figures 26, 27 and 29, and the yield is 79.7%.

Example 12

Rapid synthesis of nano-scale CD-MOF crystal by ultrasonic method

And (3) ultrasonically heating a mixed system of the gamma-cyclodextrin, KOH aqueous solution and a part of organic solvent by using an ultrasonic mode. 163.0mg of gamma-CD and 56.0mg of KOH mixture (the molar ratio of gamma-CD to KOH is 0.125) are weighed and dissolved in 5mL of water, 3mL of methanol is added into the mixed solution in advance, a 40KHz ultrasonic reactor is used, the power is set to 40W, the temperature is 50 ℃, the supernatant is taken out after 20min of reaction, 8mL of methanol is added, 64mg of PEG20000 is added, after the mixture is kept stand for half an hour, the mixture is centrifuged at 3000rpm for 5min, ethanol (10mL multiplied by 2) and dichloromethane (10mL multiplied by 2) are respectively used for washing, and the obtained crystals are dried in vacuum at 50 ℃ for 12h to obtain second-stage nanoscale CD-MOF crystals (CD-MOF Nano), wherein the size is 200 and 500nm, and the yield is 85.2% as shown in FIGS. 28 and 30.

As described in the above examples, the method of the present invention can be completed in a few minutes to a few hours, and has the advantages of rapidness, simplicity, safety, high yield, etc.

The dimensional and yield data for the portions of the product produced in the above examples are summarized in the table below.

Example 13

Preparation of alkaline micron-sized CD-MOF crystals for improving thermal stability of sucralose

Dissolving gamma-CD and KOH in water, adding a proper amount of methanol into the mixed solution of the gamma-CD and the KOH, and heating in a closed container to evaporate methanol steam into a mixed system of the gamma-CD and the KOH. After reacting for a certain time, taking out the supernatant, adding polyethylene glycol 4000, standing for a certain time, washing with ethanol and dichloromethane, and vacuum drying the obtained crystals to obtain the alkaline micron-sized CD-MOF with the yield of about 80%.

Weighing the prepared alkaline micron-sized CD-MOF, adding a sucralose ethanol solution (the feeding molar ratio of the CD-MOF to the sucralose is 1:7 according to the ratio of cyclodextrin to sucralose), shaking and incubating for a certain time at 37 ℃, centrifuging, and vacuum-drying the lower-layer precipitate to obtain the sucralose-loaded alkaline micron-sized CD-MOF compound. Weighing a certain amount of sucralose-loaded alkaline micron-sized CD-MOF compound in a penicillin bottle, placing the penicillin bottle in an oven at 90 ℃, precisely weighing a certain amount of samples respectively at 0 hour, 1 hour, 2 hours, 4 hours, 8 hours, 16 hours and 24 hours, dissolving the samples in a certain amount of water, and determining the content of sucralose by using a high performance liquid chromatography-evaporative light scattering detector method (HPLC-ELSD). Calculating the residual rate of the sucralose content in the heated sample, wherein the residual rate is the sucralose content after heating/the sucralose content before heating multiplied by 100%.

The thermal stability results are shown in FIG. 31, where sucralose degraded 90% at 90 ℃ for 2 h. Under the same conditions, sucralose in the sucralose-loaded alkaline micron-sized CD-MOF composite degrades by 13% in 2 hours and by 45% in 24 hours. Compared with sucralose, the sucralose-loaded alkaline micron-sized CD-MOF compound has obviously improved thermal stability.

The sucralose-loaded alkaline micro-sized CD-MOF complex of this example was determined to have a sucralose content of 18% (w/w), wherein the molar ratio of cyclodextrin to sucralose was 1: 0.8.

Example 14

Preparation of alkaline nanoscale CD-MOF crystals for improving thermal stability of sucralose

Dissolving gamma-CD and KOH in water, adding a proper amount of methanol into the mixed solution of the gamma-CD and the KOH, and heating in a closed container to evaporate methanol steam into a mixed system of the gamma-CD and the KOH. After reacting for a certain time, taking out the supernatant, adding methanol with the same volume, adding polyethylene glycol 4000, standing for a certain time, washing with ethanol and dichloromethane, and vacuum drying the obtained crystals to obtain the alkaline nanoscale CD-MOF with the yield of about 80%.

Weighing the prepared alkaline nanoscale CD-MOF, adding a sucralose methanol solution (the feeding molar ratio of the CD-MOF to the sucralose is 1:7 according to the ratio of cyclodextrin to sucralose), shaking and incubating for a certain time at 37 ℃, centrifuging, and vacuum-drying the lower-layer precipitate to obtain the sucralose-carrying alkaline nanoscale CD-MOF compound. The complex was subjected to thermal analysis: weighing a certain amount of sample, putting the sample into an alumina crucible, introducing high-purity nitrogen for purging, heating to 400 ℃ from 30 ℃ at a heating rate of 10 ℃/min, monitoring the weight loss percentage of the sample, and carrying out thermogravimetric analysis (TGA) on the sample; weighing a certain amount of sample, using a Differential Scanning Calorimeter (DSC), heating to 300 ℃ from 40 ℃ at a heating rate of 10 ℃/min, monitoring the change of heat flow, and recording a DSC curve.

The thermal stability results are shown in FIG. 32, where sucralose degraded 90% at 90 ℃ for 2 h. Under the same conditions, sucralose in the sucralose-loaded basic nanoscale CD-MOF complex degrades by 45% at 2h and by 53% at 24 h. Compared with sucralose, the sucralose-loaded alkaline nanoscale CD-MOF compound has obviously improved thermal stability.

In addition, the thermal analysis results showed that the thermal decomposition temperature of sucralose was 124.2 ℃ (as shown in fig. 33), while the thermal decomposition temperature of sucralose-loaded basic nanoscale CD-MOF complex was 206.2 ℃ (as shown in fig. 34), and the thermal stability of sucralose-loaded basic nanoscale CD-MOF complex was significantly improved compared to sucralose.

The sucralose-loaded basic nanoscale CD-MOF complex of this example was determined to have a sucralose content of 28% (w/w), wherein the molar ratio of cyclodextrin to sucralose was 1: 1.4.

The results show that the sucralose-loaded basic nanoscale CD-MOF compound obtained under the same feeding ratio and incubation conditions has higher sucralose loading than the sucralose-loaded basic microscale CD-MOF compound. However, the thermal stability of sucralose-loaded basic microscale CD-MOF complexes is superior to sucralose-loaded basic nanoscale CD-MOF complexes.

Example 15

Neutral micron-sized CD-MOF compound for improving thermal stability of sucralose

Weighing a certain amount of the alkaline micron-sized CD-MOF prepared in the example 13, dispersing the alkaline micron-sized CD-MOF into absolute ethyl alcohol containing glacial acetic acid, shaking and incubating for a certain time in a shaking table, washing with ethyl alcohol, collecting solids, and drying in vacuum to obtain the neutral micron-sized CD-MOF. The preparation method and stability investigation method of the sucralose-loaded neutral micron-sized CD-MOF compound are the same as in example 13.

The thermal stability results are shown in FIG. 35, where sucralose degraded 90% at 90 ℃ for 2 h. Under the same conditions, the sucralose in the sucralose-loaded neutral micron-sized CD-MOF compound is not degraded in 4 hours, is degraded in 4 hours and is degraded in 27 percent in 24 hours. Compared with sucralose, the sucralose-loaded neutral micron-sized CD-MOF compound has obviously improved thermal stability.

The sucralose-loaded neutral micro-sized CD-MOF complex of this example was determined to have a sucralose content of 15% (w/w), wherein the molar ratio of cyclodextrin to sucralose was 1: 0.6.

The results show that the sucralose-loaded neutral micron-sized CD-MOF complexes obtained under the same charge ratio and incubation conditions have substantially the same sucralose loading as the sucralose-loaded basic micron-sized CD-MOF complexes. However, the thermal stability of the sucralose-loaded neutral microscale CD-MOF complexes was significantly improved compared to the sucralose-loaded basic microscale CD-MOF complexes.

Example 16

Neutral nanoscale CD-MOF complexes for enhancing sucralose thermal stability

Weighing a certain amount of the alkaline nanoscale CD-MOF prepared in the example 14, dispersing the alkaline nanoscale CD-MOF into absolute ethyl alcohol containing glacial acetic acid, shaking and incubating for a certain time in a shaking table, washing with ethyl alcohol, collecting solids, and performing vacuum drying to obtain the neutral nanoscale CD-MOF. The preparation method and stability of the neutral nanometer CD-MOF compound carrying the sucralose are the same as in example 13, but the incubation temperature is 25 ℃, wherein the feeding molar ratio of the CD-MOF to the sucralose is 1:7 according to the ratio of the cyclodextrin to the sucralose.

The content (w/w) of sucralose in the obtained complex is 23%, wherein the molar ratio of cyclodextrin to sucralose is 1: 1.1. The thermal stability results are shown in FIG. 36, where sucralose degraded 90% at 90 ℃ for 2 h. Under the same conditions, the sucralose in the sucralose-loaded neutral nano-sized CD-MOF compound is degraded by 3% in 8 hours and 14% in 24 hours. Compared with sucralose, the sucralose-loaded neutral nanoscale CD-MOF compound has obviously improved thermal stability. In addition, the thermal decomposition temperature of the sucralose-loaded neutral nanoscale CD-MOF complex was 212.0 ℃, and the thermal stability of the sucralose-loaded neutral nanoscale CD-MOF complex was significantly improved compared to sucralose, as shown in fig. 37 and 43.

After the alkaline micro-scale CD-MOFs and the alkaline nano-scale CD-MOFs are respectively acidified into corresponding neutral micro-scale CD-MOFs and neutral nano-scale CD-MOFs, the crystallinity and the crystal morphology of the CD-MOFs are not changed, as shown in FIGS. 38 and 39.

The results show that the sucralose-loaded neutral nanoscale CD-MOF complex obtained under the same charge ratio and incubation conditions has slightly lower sucralose loading than the sucralose-loaded basic nanoscale CD-MOF complex. However, the thermal stability of the sucralose-loaded neutral nanoscale CD-MOF complexes was significantly improved compared to the sucralose-loaded basic nanoscale CD-MOF complexes (example 14). In addition, compared with the neutral micro-sized CD-MOF compound carrying the sucralose, the loading capacity and the thermal stability of the neutral nano-sized CD-MOF compound carrying the sucralose are obviously improved.

In summary, the thermostability of the sucralose-loaded CD-MOF complex under the same feed ratio and incubation conditions was as follows:

sucralose-loaded neutral nanoscale CD-MOF complexes > sucralose-loaded neutral microscale CD-MOF complexes > sucralose-loaded basic nanoscale CD-MOF complexes

Example 17

Neutral nanoscale CD-MOF complexes for enhancing sucralose thermal stability

The sucralose-loaded neutral nanoscale CD-MOF complex was prepared as in example 16, but the charged molar ratio of CD-MOF to sucralose was 1:1, calculated as the ratio of cyclodextrin to sucralose.

The content (w/w) of sucralose in the obtained complex is 5%, wherein the molar ratio of cyclodextrin to sucralose is 1: 0.2. The thermal stability results show that sucralose in the complex degrades by 53% at 24 h. The thermal stability of the sucralose-loaded neutral nanoscale CD-MOF complexes was significantly improved compared to sucralose, as shown in figure 40.

Example 18

Neutral nanoscale CD-MOF complexes for enhancing sucralose thermal stability

The sucralose-loaded neutral nanoscale CD-MOF complex was prepared as in example 16, but the charged molar ratio of CD-MOF to sucralose was 1:3, calculated as the ratio of cyclodextrin to sucralose.

The content (w/w) of sucralose in the obtained complex is 12%, wherein the molar ratio of cyclodextrin to sucralose is 1: 0.5. The thermal stability results show that sucralose in the complex degrades by 22% at 24 h. The thermal stability of the sucralose-loaded neutral nanoscale CD-MOF complexes was significantly improved compared to sucralose, as shown in figure 40.

Example 19

Neutral nanoscale CD-MOF complexes for enhancing sucralose thermal stability

The sucralose-loaded neutral nanoscale CD-MOF complex was prepared as in example 16, but the charged molar ratio of CD-MOF to sucralose was 1:5, calculated as the ratio of cyclodextrin to sucralose.

The content (w/w) of sucralose in the obtained complex was 17%, wherein the molar ratio of cyclodextrin to sucralose was 1: 0.8. The thermal stability results show that sucralose in the complex degrades by 17% at 24 h. The thermal stability of the sucralose-loaded neutral nanoscale CD-MOF complexes was significantly improved compared to sucralose, as shown in figure 40.

When the neutral nano-scale CD-MOF compound carrying the sucralose is prepared, the charging molar ratio of the CD-MOF to the sucralose is 1:5 and 1:7 according to the ratio of the cyclodextrin to the sucralose, the thermal stability of the sucralose in the obtained compound is highest, and the thermal stability is higher when the ratio is 1: 3. The thermal stability of the sucralose-loaded neutral nanoscale CD-MOF complexes was significantly improved compared to sucralose, as shown in figure 40.

The following table summarizes the thermal stability data (sucralose residual rate) for sucralose-loaded neutral nanoscale CD-MOF complexes for different CD-MOF to sucralose feed molar ratios

It can also be seen from the above table that when the charged molar ratio of CD-MOF to sucralose is calculated as 1:5 and 1:7 according to the ratio of cyclodextrin to sucralose, the sucralose content in the resulting composite is 17% and 23%, respectively, and the sucralose thermal stability in the composite is the highest. The feeding molar ratio is calculated as 1:1 and 1:3 according to the ratio of cyclodextrin to sucralose, the content of sucralose in the obtained compound is 5% and 12% respectively, the thermal stability of sucralose in the compound is relatively poor, and the feeding molar ratio is lower than the stability of the compound obtained by calculating as 1:5 and 1:7 according to the ratio of cyclodextrin to sucralose. The above results are quite unexpected, and according to the conventional knowledge of those skilled in the art, the carrier CD-MOF has a protective effect on sucralose, and the higher the proportion of the carrier CD-MOF, i.e. cyclodextrin, in the composite, the more sufficient the protection on sucralose is, the better the stability of sucralose in the composite should be, however, the opposite is true, and the higher the content of sucralose in the composite is rather beneficial to improve the stability of sucralose in the composite.

Example 20

Neutral nanoscale CD-MOF complexes for enhancing sucralose thermal stability

The sucralose-loaded neutral nanoscale CD-MOF complex was prepared as in example 16, but the charged molar ratios of CD-MOF to sucralose were 1:11, 1:14, 1:21, and 1:28, respectively, as calculated from the ratio of cyclodextrin to sucralose.

The content (w/w) of sucralose in the obtained complex is 23%, 24%, 25% and 24%, respectively, wherein the molar ratio of cyclodextrin to sucralose is 1:1.1, 1:1.2 and 1:1.1, respectively. The thermal stability results indicated that sucralose in the complex degraded 11%, 17%, 13%, and 12% at 24 h. Compared with the neutral nano-scale CD-MOF compound (the content of sucralose in the compound is 23 percent, and the sucralose is degraded by 14 percent at 24 hours) obtained by adding the compound with the molar ratio of 1:7 according to the ratio of cyclodextrin to sucralose, the compound obtained by further increasing the adding amount of sucralose has no remarkable increase in the loading amount of sucralose and no remarkable increase in the stability of sucralose, as shown in FIG. 40.

Example 21

The sucralose-loaded neutral micro-sized CD-MOF complex was prepared in the same manner as in example 15, except that the charge molar ratio of CD-MOF to sucralose was 1:1, calculated as the ratio of cyclodextrin to sucralose.

The content (w/w) of sucralose in the obtained complex is 3%, wherein the molar ratio of cyclodextrin to sucralose is 1: 0.1. The thermal stability results indicated that sucralose in the complex degraded 52% at 24 h. The thermal stability of sucralose-loaded neutral micrometer-sized CD-MOF complexes was significantly improved compared to sucralose, as shown in fig. 41.

Example 22

The sucralose-loaded neutral micro-sized CD-MOF complex was prepared in the same manner as in example 15, except that the charge molar ratio of CD-MOF to sucralose was 1:3, calculated as the ratio of cyclodextrin to sucralose.

The content (w/w) of sucralose in the obtained complex was 9%, wherein the molar ratio of cyclodextrin to sucralose was 1: 0.4. The thermal stability results show that sucralose in the complex degrades by 30% at 24 h. The thermal stability of sucralose-loaded neutral micrometer-sized CD-MOF complexes was significantly improved compared to sucralose, as shown in fig. 41.

Example 23

The sucralose-loaded neutral micro-sized CD-MOF complex was prepared in the same manner as in example 15, except that the charge molar ratio of CD-MOF to sucralose was 1:5, calculated as the ratio of cyclodextrin to sucralose.

The content (w/w) of sucralose in the obtained complex is 14%, wherein the molar ratio of cyclodextrin to sucralose is 1: 0.6. The thermal stability results show that sucralose in the complex degrades by 2% at 24 h. The thermal stability of sucralose-loaded neutral micrometer-sized CD-MOF complexes was significantly improved compared to sucralose, as shown in fig. 41.

When the charging molar ratio of the CD-MOF to the sucralose is 1:5 according to the ratio of the cyclodextrin to the sucralose when preparing the sucralose-carrying neutral micron-sized CD-MOF composite, the thermal stability of the sucralose in the obtained composite is the highest, and the ratios are 1:3 and 1: the thermal stability at 7 is also relatively high. The thermal stability of sucralose-loaded neutral micrometer-sized CD-MOF complexes was significantly improved compared to sucralose, as shown in fig. 41.

The following table summarizes the thermal stability data (sucralose residual rate) of sucralose-loaded neutral micro-sized CD-MOF complexes for different CD-MOF to sucralose feed molar ratios

Example 24

Basic nanoscale CD-MOF complex for improving thermal stability of sucralose

Sucralose-loaded basic nanoscale CD-MOF complexes were prepared as in example 14, but with the charge molar ratio of CD-MOF to sucralose being 1:1, calculated as the ratio of cyclodextrin to sucralose.

The content (w/w) of sucralose in the obtained complex is 5%, wherein the molar ratio of cyclodextrin to sucralose is 1: 0.2. The thermal stability results show that sucralose in the complex degrades by 91% at 24 h. The thermal stability of sucralose-loaded neutral micrometer-sized CD-MOF complexes was significantly improved compared to sucralose, as shown in fig. 42.

Example 25

Basic nanoscale CD-MOF complex for improving thermal stability of sucralose

Sucralose-loaded basic nanoscale CD-MOF complexes were prepared as in example 14, but with the charge molar ratio of CD-MOF to sucralose being 1:3, calculated as the ratio of cyclodextrin to sucralose.

The content (w/w) of sucralose in the obtained complex is 12%, wherein the molar ratio of cyclodextrin to sucralose is 1: 0.5. The thermal stability results show that sucralose in the complex degrades by 63% at 24 h. The thermal stability of sucralose-loaded neutral micrometer-sized CD-MOF complexes was significantly improved compared to sucralose, as shown in fig. 42.

Example 26

Basic nanoscale CD-MOF complex for improving thermal stability of sucralose

Sucralose-loaded basic nanoscale CD-MOF complexes were prepared as in example 14, but with the charge molar ratio of CD-MOF to sucralose being 1:5, calculated as the ratio of cyclodextrin to sucralose.

The content (w/w) of sucralose in the obtained complex was 17%, wherein the molar ratio of cyclodextrin to sucralose was 1: 0.7. The thermal stability results indicated that sucralose in the complex degraded 54% at 24 h. The thermal stability of sucralose-loaded neutral micrometer-sized CD-MOF complexes was significantly improved compared to sucralose, as shown in fig. 42.

When the basic nanometer CD-MOF compound carrying the sucralose is prepared, the thermal stability of the sucralose in the obtained compound is higher when the charging molar ratio of the CD-MOF to the sucralose is 1:3, 1:5 or 1:7 according to the ratio of the cyclodextrin to the sucralose. The thermal stability of sucralose-loaded basic nanoscale CD-MOF complexes was significantly improved compared to sucralose, as shown in figure 42.

The following table summarizes the thermal stability data (sucralose residual rate) for sucralose-loaded basic nanoscale CD-MOF complexes for different CD-MOF to sucralose feed molar ratios

Molar ratio/time	1h	8h	24h
				1:1	80.1	25.7	8.9
1:3	90.0	38.4	37.3
				1:5	90.3	49.4	46.2
1:7	91.2	49.8	47.3

Example 27

Alkaline micron-sized CD-MOF compound for improving thermal stability of sucralose

Sucralose-loaded alkaline microscale CD-MOF complexes were prepared as in example 13, but with the charge molar ratio of CD-MOF to sucralose being 1:1, calculated as the ratio of cyclodextrin to sucralose.

The content (w/w) of sucralose in the obtained complex is 6%, wherein the molar ratio of cyclodextrin to sucralose is 1: 0.2. The thermal stability results indicated that sucralose in the complex degraded 84% at 24 h. The thermal stability of sucralose-loaded neutral micrometer-sized CD-MOF complexes was significantly improved compared to sucralose, as shown in fig. 43.

Example 28

Sucralose-loaded alkaline microscale CD-MOF complexes were prepared as in example 13, except that the charge molar ratio of CD-MOF to sucralose was 1:3, calculated as the ratio of cyclodextrin to sucralose.

The content (w/w) of sucralose in the obtained complex is 10%, wherein the molar ratio of cyclodextrin to sucralose is 1: 0.4. The thermal stability results indicated that sucralose in the complex degraded 68% at 24 h. The thermal stability of sucralose-loaded neutral micrometer-sized CD-MOF complexes was significantly improved compared to sucralose, as shown in fig. 43.

Example 29

Sucralose-loaded alkaline microscale CD-MOF complexes were prepared as in example 13, but with a molar ratio of CD-MOF to sucralose of 1:5, calculated as the ratio of cyclodextrin to sucralose.

The content (w/w) of sucralose in the obtained complex is 13%, wherein the molar ratio of cyclodextrin to sucralose is 1: 0.5. The thermal stability results show that sucralose in the complex degrades by 63% at 24 h. The thermal stability of sucralose-loaded neutral micrometer-sized CD-MOF complexes was significantly improved compared to sucralose, as shown in fig. 43.

When the molar ratio of the charged CD-MOF to the sucralose is 1:7 calculated according to the ratio of the cyclodextrin to the sucralose when preparing the sucralose-loaded alkaline micron-sized CD-MOF composite, the sucralose in the obtained composite has the highest thermal stability, and the stability is also higher when the ratio is 1:3 or 1: 5. The thermal stability of sucralose-loaded alkaline microscale CD-MOF complexes was significantly improved compared to sucralose, as shown in fig. 43.

The following table summarizes the thermal stability data (sucralose residual rate) of sucralose-loaded alkaline microscale CD-MOF complexes for different CD-MOF to sucralose charge molar ratios

Molar ratio/time	1h	8h	24h
				1:1	78.8	29.0	16.3
1:3	91.4	53.9	32.3
				1:5	90.8	59.2	37.3
1:7	91.0	65.7	55.5

Example 30

Preparation of sucralose/beta-cyclodextrin inclusion compound

1135mg of beta-cyclodextrin (1mmol) is weighed and dissolved in 30mL of water, 397mg of sucralose (1mmol) is weighed and dissolved in 15mL of ethanol, the sucralose solution is dropwise added into the beta-cyclodextrin aqueous solution in a stirring state, the temperature is maintained at 40 ℃, the stirring is continued at 500rpm for 3 hours, and the ethanol is removed. And freeze-drying the rest liquid to obtain the sucralose/beta-cyclodextrin inclusion compound. The thermal analysis method was the same as in example 14.

The thermal gravimetric analysis result shows that the thermal decomposition temperature of the sucralose/beta-cyclodextrin inclusion compound is 127.5 ℃, as shown in fig. 44. The sucralose/beta-cyclodextrin inclusion compound had little protective effect on sucralose, as shown in fig. 46 and 47.

Example 31

Preparation of sucralose/gamma-cyclodextrin inclusion compound

1297mg of gamma-cyclodextrin (1mmol) is weighed and dissolved in 30mL of water, 397mg of sucralose (1mmol) is weighed and dissolved in 15mL of ethanol, the sucralose solution is dripped into the gamma-cyclodextrin aqueous solution under stirring, the temperature is maintained at 40 ℃, the stirring is continued at 500rpm for 3h, and the ethanol is removed. And freeze-drying the rest liquid to obtain the sucralose/gamma-cyclodextrin inclusion compound. The thermal analysis method was the same as in example 14.

The results of thermogravimetric analysis showed that the decomposition temperature of the sucralose/γ -cyclodextrin inclusion compound was 173.4 ℃, as shown in fig. 45. Sucralose/gamma-cyclodextrin inclusion compounds can improve the thermal stability of sucralose, as shown in fig. 46 and 47.

The above results indicate that sucralose cannot be protected or is not well protected by the cyclodextrin alone to encapsulate sucralose.

All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims

1. A method for preparing a sucralose-loaded cyclodextrin-metal-organic framework complex, comprising the steps of:

(I) providing a cyclodextrin-metal organic framework material;

the feeding mol of the cyclodextrin-metal organic framework material and the sucralose is 1 (1-10), wherein the molar weight of the cyclodextrin-metal organic framework material is calculated according to the molar weight of the cyclodextrin; and

(III) optionally separating and/or drying the sucralose-loaded cyclodextrin-metal-organic framework complex precipitated in step (II);

wherein the metal ions of the cyclodextrin-metal organic framework material are selected from the group consisting of: li⁺、K⁺、Rb⁺、Cs⁺、Na⁺、Mg²⁺、Cd²⁺、Sn²⁺、Ag⁺、Yb⁺、Ba²⁺、Sr²⁺、Ca²⁺、Pb²⁺、La³⁺Or a combination thereof.

2. The method of claim 1, wherein the molar ratio of cyclodextrin-metal organic framework material to sucralose is 1 (3-8).

3. The method of claim 1, wherein the molar charge of the cyclodextrin-metal organic framework material and the sucralose is 1 (5-7).

4. The method of claim 1, wherein the sucralose-loaded cyclodextrin-metal-organic framework complex has one or more characteristics selected from the group consisting of:

(1) the thermal decomposition temperature of the sucralose in the compound is 200-500 ℃;

(2) heat treatment is carried out for 24 hours at the temperature of 90 ℃, and the degradation of the sucralose in the compound is less than or equal to 60 percent;

(3) the mol ratio of cyclodextrin to sucralose in the compound is 1 (0.3-2);

(4) the content (w/w) of the sucralose in the compound is more than or equal to 5 percent;

(5) the thermal decomposition temperature of the sucralose in the compound is increased by more than or equal to 80 ℃ compared with the thermal decomposition temperature of the free sucralose.

5. The method of claim 4, wherein the thermal decomposition temperature of sucralose in said complex is 210-300 ℃.

6. The method of claim 4, wherein the sucralose in said complex degrades by less than or equal to 20%.

7. The method of claim 4, wherein the sucralose in said complex degrades by less than or equal to 5%.

8. The method of claim 4, wherein the molar ratio of cyclodextrin to sucralose in the complex is 1 (0.5-1.8).

9. The method of claim 4, wherein the molar ratio of cyclodextrin to sucralose in the complex is 1 (0.8-1.5).

10. The method of claim 4, wherein the sucralose content (w/w) of said complex is greater than or equal to 15%.

11. The method of claim 4, wherein the sucralose content (w/w) of said complex is greater than or equal to 25%.

12. The method of claim 4, wherein the thermal decomposition temperature of sucralose in said complex is increased by greater than or equal to 88 ℃ from the thermal decomposition temperature of free sucralose.

13. The method of claim 1, wherein the cyclodextrin-metal-organic framework material comprises a nanoscale cyclodextrin-metal-organic framework material and a microscale cyclodextrin-metal-organic framework material.

14. The method of claim 1, wherein the cyclodextrin-metal-organic framework material comprises an acidified cyclodextrin-metal-organic framework material and/or a basic cyclodextrin-metal-organic framework material;

wherein the acidified cyclodextrin-metal organic framework material has the following characteristics: dissolving the acidified cyclodextrin-metal organic framework material in water to prepare 10mg/mL aqueous solution, wherein the pH value of the aqueous solution is 5-8;

the basic cyclodextrin-metal organic framework material has the following characteristics: when the basic cyclodextrin-metal organic framework material is dissolved in water to prepare 10mg/mL aqueous solution, the pH value of the aqueous solution is 11-13.

15. The method of claim 14, wherein the basic cyclodextrin-metal organic framework material is acidified to obtain the acidified cyclodextrin-metal organic framework material.

16. The method of claim 15, wherein said acidizing comprises the steps of:

17. The method of claim 16, wherein the acid is an organic acid or an inorganic acid.

18. The method of claim 1, wherein the temperature of the shaking incubation treatment is 25-45 ℃.

19. The method of claim 1, wherein in step (II), the treatment time of the shaking incubation treatment is 12-72 h.

20. The method of claim 1, wherein in step (I), further comprising the step of preparing a basic cyclodextrin-metal organic framework material:

wherein the volume ratio of the first organic solvent to the first mixed solution is (0.01-5) to 1;

21. The method of claim 20, wherein the concentration of metal ions in the first mixed solution is between 0.05M and 0.4M.

22. The method of claim 20, wherein the concentration of metal ions in the first mixed solution is between 0.1M and 0.3M.

23. The method of claim 20, wherein the concentration of cyclodextrin in the first mixed solution is 0.013 to 0.05M.

24. The method of claim 20, wherein the concentration of cyclodextrin in the first mixed solution is 0.02 to 0.03M.

25. The method of claim 20, wherein the molar ratio of cyclodextrin to metal ion in the first mixed solution is from 1: (6-10).

26. The method of claim 20, wherein the metal ion is selected from the group consisting of: li⁺、K⁺、Rb⁺、Cs⁺、Na⁺Or a combination thereof.

27. The method according to claim 20, wherein in the step (5), the volume ratio of the second organic solvent to the third mixed solution is (0.01-5): 1.

28. The method according to claim 20, wherein in the step (5), the volume ratio of the second organic solvent to the third mixed solution is (0.5-2): 1.

29. The method of claim 20, wherein the size-adjusting agent comprises polyethylene glycol, povidone, polysorbate, sorbitan monolaurate, polyoxyethylene lauryl ether, emulsifier OP (polyoxyethylene nonyl phenol ether condensate), lactofen a (polyoxyethylene fatty alcohol ether), pluronic (polyoxyethylene polypropylene glycol condensate), sodium lauryl sulfate, sodium dodecylbenzenesulfonate, dodecyldimethylbenzyl ammonium bromide (benzalkonium bromide), or a combination thereof.

30. The method of claim 1, wherein in step (I), further comprising the step of preparing a basic cyclodextrin-metal organic framework material:

wherein the volume ratio of the first organic solvent to the first mixed solution is (0.01-0.5) to 1;

(a) carrying out solvent thermal volatilization treatment;

31. A complex comprising (a) a cyclodextrin-metal organic framework material; and (b) sucralose supported on said framework material;

wherein the molar ratio of cyclodextrin to sucralose in the complex is 1 (0.3-2);

wherein the metal ion of the cyclodextrin-metal organic framework materialAnd is selected from the group consisting of: li⁺、K⁺、Rb⁺、Cs⁺、Na⁺、Mg²⁺、Cd²⁺、Sn²⁺、Ag⁺、Yb⁺、Ba²⁺、Sr²⁺、Ca²⁺、Pb²⁺、La³⁺Or a combination thereof.

32. A sucralose-loaded cyclodextrin-metal-organic framework complex prepared by the method of claim 1.

33. The complex of claim 31 or 32, wherein the complex further has one or more characteristics selected from the group consisting of:

(3) the mol ratio of cyclodextrin to sucralose in the compound is 1 (0.5-1.8);