An illite@γ-CD-MOF composite drug delivery material, its preparation method and application

Abstract

This invention discloses an illite@γ-CD-MOF composite drug-loaded material, its preparation method, and its applications. The illite@γ-CD-MOF composite drug-loaded material is obtained by reacting illite, γ-CD-MOF, and minoxidil in an ethanol solution. The illite@γ-CD-MOF composite drug-loaded material provided by this invention not only has a good appearance but also high drug loading capacity and high potassium ion release rate. When the illite@γ-CD-MOF composite drug-loaded material is blended with PVA to form an illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film, its use not only reduces scalp damage from direct application but also allows for safer and more effective drug delivery, with a high drug release rate, demonstrating significant application value.

Description

Technical Field

[0001] This invention relates to an illite@γ-CD-MOF composite drug-loaded material, its preparation method, and its application, belonging to the field of drug-loaded material technology. Background Technology

[0002] Currently available medications for treating hair loss include finasteride, spironolactone, and minoxidil. Finasteride is only suitable for male patients, and some patients may experience side effects such as decreased prostate-specific antigen (PSA) and allergic reactions. Spironolactone is only suitable for some female patients with androgenetic alopecia (AGA), and it takes more than a year to see results; it may also cause adverse reactions such as menstrual irregularities and breast tenderness. Minoxidil, as an effective topical medication that promotes hair growth, is well-tolerated, with a low incidence and mild symptoms of adverse reactions. However, minoxidil has extremely poor water solubility, which limits its application.

[0003] Metal-organic frameworks (MOFs) are a new type of hybrid material composed of metal ions linked to organic ligands. They are synthesized using numerous methods, exhibiting diverse structures and compositions, and possessing many properties suitable for drug delivery, such as: (1) the relatively unstable coordination bonds between metal ions and ligands make them biodegradable, and most of their components are non-toxic to humans, thus enabling their application in the biomedical field; (2) they possess regular pores and relatively stable structures, and the size, structure, and chemical properties of the pores can be adjusted by selecting different metals and organic ligands; (3) their large surface area and adjustable pore size allow them to load a large number of different drug molecules; (4) they have structural modifiability, enabling slow or controlled release of the loaded drug molecules, and also increasing biocompatibility and targeting. In 2010, Smallone et al. successfully obtained an edible cyclodextrin-MOF through a simple slow evaporation method, thus opening up the application of MOFs in the biomedical field.

[0004] γ-CD-MOF (γ-cyclodextrin metal-organic framework) is a three-dimensional ordered green material mainly formed by the coordination of alkali metals (such as potassium K) with γ-CD. The components of this material are safe and non-toxic, exhibiting good biocompatibility. It can address the shortcomings of MOFs in practical drug delivery. Furthermore, it possesses both hydrophilic and hydrophobic pores, allowing it to encapsulate both hydrophobic and hydrophilic drugs. It can also effectively improve the stability of guest drug molecules and enhance efficacy, making it a highly promising drug carrier.

[0005] Using γ-CD-MOF as a drug carrier to load minoxidil, a drug for treating hair loss, would be significant for improving its pharmacokinetic properties, increasing bioavailability, reducing toxicity, and achieving controlled release. However, γ-CD-MOF currently has low drug loading capacity and potassium ion release rate, which cannot meet the requirements for drug delivery applications. Therefore, it is necessary to develop a novel drug-loaded material with high drug loading capacity and controllable minoxidil release. Summary of the Invention

[0006] In view of the above-mentioned problems and needs of the existing technology, the purpose of this invention is to provide an illite@γ-CD-MOF composite drug-loaded material containing minoxidil, a drug for treating hair loss, as well as its preparation method and application.

[0007] To achieve the above-mentioned objectives, the technical solution adopted by the present invention is as follows:

[0008] An illite@γ-CD-MOF composite drug delivery material is obtained by reacting illite, γ-CD-MOF and minoxidil ethanol solution.

[0009] In a preferred embodiment, the concentration of the minoxidil ethanol solution is 1–5 mg / mL.

[0010] In a preferred embodiment, the addition ratio of illite:γ-CD-MOF:minoxidil ethanol solution is (1-5g):(1-5g):(100-300mL).

[0011] In a preferred embodiment, the illite is illite purified by gravity separation or illite calcined at high temperature.

[0012] One implementation scheme, gravity separation for purifying illite, includes the following steps:

[0013] The raw illite powder is evenly dispersed in water and allowed to stand for 6 to 10 hours. The supernatant is then discarded, and the remaining material is separated into solid and liquid components by centrifugation. The separated solid is then washed by centrifugation and dried at 90 to 110°C to obtain purified illite.

[0014] In a preferred embodiment, the virgin illite powder is uniformly dispersed in water. The specific operation is as follows: the virgin illite powder is added to water, ultrasonically dispersed for 10 to 50 minutes, and then stirred to make it uniformly dispersed in water. The ratio of virgin illite powder to water is (10 to 50 g): (200 to 1000 mL).

[0015] One embodiment involves high-temperature calcination of illite, comprising the following steps:

[0016] The raw illite powder is placed in a muffle furnace (specifically, the raw illite powder is first placed in a crucible, and then the crucible containing the raw illite powder is placed in the muffle furnace), and the temperature is raised to 300-800°C at a heating rate of 5-10°C / min. After calcination for 3-8 hours, it is naturally cooled to room temperature to obtain the high-temperature calcined illite.

[0017] In one embodiment, the γ-CD-MOF is obtained by vapor diffusion reaction of γ-cyclodextrin with a water-soluble potassium salt, wherein the molar ratio of γ-cyclodextrin to water-soluble potassium salt is 1:(6-12).

[0018] In a preferred embodiment, the water-soluble potassium salt is any one of potassium carbonate, potassium hydroxide, potassium chloride, and potassium sulfate.

[0019] A preferred embodiment of the vapor diffusion method for preparing γ-CD-MOF includes the following steps:

[0020] γ-Cyclodextrin and a water-soluble potassium salt are dissolved in water to obtain a mixed solution. The mixed solution is filtered through a filter membrane into a reaction vessel (e.g., a glass tube). The reaction vessel is then placed in a methanol vapor atmosphere to allow the methanol vapor to diffuse into the solution for 3–8 hours (specifically, the reaction vessel containing the mixed solution is placed in a methanol container containing methanol, the methanol container is then sealed, and the methanol container is heated to allow the methanol vapor to diffuse into the solution in the reaction vessel for 3–8 hours). The supernatant is then removed, and an aqueous solution of hexadecyltrimethylammonium bromide and methanol are added to the supernatant. The resulting suspension is incubated at room temperature for 3–8 hours, and the precipitate is collected by centrifugation. The collected precipitate is washed with methanol and then vacuum dried at 40–60°C for 8–12 hours to obtain crystalline γ-CD-MOF.

[0021] In a preferred embodiment, the feeding ratio of γ-cyclodextrin:water-soluble potassium salt:water in the mixed solution is (3-7g):(1-5g):(80-120mL).

[0022] In a preferred embodiment, the concentration of the hexadecyltrimethylammonium bromide aqueous solution is 5-10 mg / mL, the volume ratio of the hexadecyltrimethylammonium bromide aqueous solution to the supernatant is 10 mL:(80-120 mL), and the volume ratio of methanol to the supernatant is (80-120 mL):(80-120 mL).

[0023] A method for preparing an illite@γ-CD-MOF composite drug delivery material includes the following steps:

[0024] Illite, γ-CD-MOF and minoxidil ethanol solution were stirred and reacted at 20-60℃ for 1-9 hours. After the reaction was completed, the solid product was collected (specifically, after the reaction was completed, the obtained product was centrifuged and the centrifuged product was vacuum dried at 40-60℃ for 8-12 hours) to obtain the illite@γ-CD-MOF composite drug-loaded material.

[0025] An application of an illite@γ-CD-MOF composite drug-loaded material involves using water as a solvent to blend the illite@γ-CD-MOF composite drug-loaded material with PVA (polyvinyl alcohol) to form a film, thereby obtaining an illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film.

[0026] One embodiment of the preparation of illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film includes the following steps:

[0027] First, PVA is dissolved in water to obtain a PVA aqueous solution. Then, illite@γ-CD-MOF composite drug-loaded material is added to the PVA aqueous solution and stirred to mix evenly. Then, ultrasonic degassing is performed for 10-30 minutes. Finally, it is poured into a mold and air-dried to obtain an illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film.

[0028] In a preferred embodiment, the concentration of the PVA aqueous solution is 8–12 wt%.

[0029] In a preferred embodiment, the amount of illite@γ-CD-MOF composite drug delivery material added is 1-9 wt% of PVA.

[0030] Compared with the prior art, the present invention has the following significant advantages:

[0031] 1. This invention prepares an illite@γ-CD-MOF composite drug-loaded material by reacting illite, γ-CD-MOF and minoxidil ethanol solution. The material not only has a good appearance (cubic shape), but also has a high drug loading capacity (up to 253.14 mg / g) and a high potassium ion release rate (the released potassium ion concentration exceeds 2 mg / L).

[0032] 2. The preparation method of this invention is simple, the conditions are mild, and it is suitable for large-scale production;

[0033] 3. The present invention uses illite@γ-CD-MOF composite drug-loaded material and PVA to form an illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film. When used, it can not only reduce the damage to the scalp caused by direct application, but also exert the drug effect more safely and effectively. Moreover, the drug release is high (the maximum drug release is close to 40%), which has significant application value. Attached Figure Description

[0034] Figure 1 This is a scanning electron microscope image of the illite@γ-CD-MOF composite drug-loaded material prepared in Example 3 of this invention;

[0035] Figure 2 This is the drug release curve of the illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film prepared in Example 3 of the present invention;

[0036] Figure 3 This is the drug release curve of the γ-CD-MOF drug-loaded material / PVA composite drug-loaded film prepared in Comparative Example 1 of this invention;

[0037] Figure 4 This is the drug release curve of the illite drug-loaded material / PVA composite drug-loaded film prepared in Comparative Example 2 of this invention. Detailed Implementation

[0038] The technical solution of the present invention will be further described in detail and completely below with reference to the embodiments.

[0039] Example 1

[0040] I. Preparation of illite@γ-CD-MOF composite drug delivery material:

[0041] a) Add the raw illite powder to water, first ultrasonically disperse for 30 minutes, then magnetically stir to make it evenly dispersed in the water. The ratio of raw illite powder to water is 20g:400mL. Then let it stand for 8 hours, discard the supernatant, and separate the remaining material (intermediate suspension and bottom impurities) into solid and liquid by centrifugation. After centrifugation and washing, the separated solid is dried at 100℃. The dried solid is ground into fine powder using a mortar and pestle to obtain the purified illite.

[0042] b) Dissolve γ-cyclodextrin and potassium hydroxide in water to obtain a mixed solution, wherein the feeding ratio of γ-cyclodextrin:potassium hydroxide:water is 3g:1g:100mL; filter the mixed solution through a 0.45μm organic filter membrane into a glass tube, then place the glass tube in a beaker containing methanol, seal the beaker and place it in a 60℃ water bath to allow methanol vapor to diffuse into the solution in the reaction vessel for 3 hours; after the reaction is completed, take out the supernatant, add an 8mg / mL hexadecyltrimethylammonium bromide aqueous solution and methanol to the supernatant to trigger rapid precipitation of the crystalline substance, wherein the volume ratio of hexadecyltrimethylammonium bromide aqueous solution:supernatant is 10mL:100mL, and the volume ratio of methanol:supernatant is 100mL:100mL; incubate the resulting suspension at room temperature for 3 hours, centrifuge to collect the precipitate, wash the collected precipitate with methanol, and then vacuum dry it at 50℃ for 12 hours to obtain crystalline γ-CD-MOF;

[0043] c) Add a 2.5 mg / mL minoxidil ethanol solution to the reaction vessel, then add purified illite and γ-CD-MOF to the minoxidil ethanol solution. The ratio of illite:γ-CD-MOF:minoxidil ethanol solution is 5 g:1 g:200 mL. After the addition is complete, stir the mixture at 30 °C for 3 hours to stop the reaction. Centrifuge the product and vacuum dry it at 50 °C for 12 hours to obtain the illite@γ-CD-MOF composite drug-loaded material.

[0044] The drug loading capacity of the illite@γ-CD-MOF composite drug-loaded material prepared in this embodiment for minoxidil was tested using an ultraviolet spectrophotometer. The test results are shown in Table 1.

[0045] II. Preparation of illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film:

[0046] First, PVA is dissolved in water at 80℃ to obtain a 10wt% PVA aqueous solution. Then, illite@γ-CD-MOF composite drug-loaded material (5wt% of PVA) is added to the PVA aqueous solution and stirred to mix evenly. The mixture is then ultrasonically degassed at room temperature for 30 minutes. Finally, it is poured into a mold and air-dried to obtain an illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film.

[0047] Example 2

[0048] I. Preparation of illite@γ-CD-MOF composite drug delivery material:

[0049] a) Add the raw illite powder to water, first ultrasonically disperse for 30 minutes, then magnetically stir to make it evenly dispersed in the water. The ratio of raw illite powder to water is 20g:400mL. Then let it stand for 8 hours, discard the supernatant, and separate the remaining material (intermediate suspension and bottom impurities) into solid and liquid by centrifugation. After centrifugation and washing, the separated solid is dried at 100℃. The dried solid is ground into fine powder using a mortar and pestle to obtain the purified illite.

[0050] b) Dissolve γ-cyclodextrin and potassium hydroxide in water to obtain a mixed solution, wherein the feeding ratio of γ-cyclodextrin:potassium hydroxide:water is 3g:1g:100mL; filter the mixed solution through a 0.45μm organic filter membrane into a glass tube, then place the glass tube in a beaker containing methanol, seal the beaker and place it in a 60℃ water bath to allow methanol vapor to diffuse into the solution in the reaction vessel for 3 hours; after the reaction is completed, take out the supernatant, add an 8mg / mL hexadecyltrimethylammonium bromide aqueous solution and methanol to the supernatant to trigger rapid precipitation of the crystalline substance, wherein the volume ratio of hexadecyltrimethylammonium bromide aqueous solution to supernatant is 10mL:100mL, and the volume ratio of methanol:supernatant is 100mL:100mL; incubate the resulting suspension at room temperature for 3 hours, centrifuge to collect the precipitate, wash the collected precipitate with methanol, and then vacuum dry it at 50℃ for 12 hours to obtain crystalline γ-CD-MOF;

[0051] c) Add a 2.5 mg / mL minoxidil ethanol solution to the reaction vessel, then add purified illite and γ-CD-MOF to the minoxidil ethanol solution. The ratio of illite:γ-CD-MOF:minoxidil ethanol solution is 5 g:1 g:200 mL. After the addition is complete, stir the mixture at 20 °C for 3 hours to stop the reaction. Centrifuge the product and vacuum dry it at 50 °C for 12 hours to obtain the illite@γ-CD-MOF composite drug-loaded material.

[0052] The drug loading capacity of the illite@γ-CD-MOF composite drug-loaded material prepared in this embodiment for minoxidil was tested using an ultraviolet spectrophotometer. The test results are shown in Table 1.

[0053] II. Preparation of illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film:

[0054] First, PVA is dissolved in water at 80℃ to obtain a 10wt% PVA aqueous solution. Then, illite@γ-CD-MOF composite drug-loaded material (5wt% of PVA) is added to the PVA aqueous solution and stirred to mix evenly. The mixture is then ultrasonically degassed at room temperature for 30 minutes. Finally, it is poured into a mold and air-dried to obtain an illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film.

[0055] Example 3

[0056] I. Preparation of illite@γ-CD-MOF composite drug delivery material:

[0057] a) First, put the raw illite powder into a crucible, then place the crucible containing the raw illite powder into a muffle furnace, heat it to 300°C at a heating rate of 10°C / min, calcine for 3 hours, and then cool it naturally to room temperature to obtain the illite after high-temperature calcination.

[0058] b) Dissolve γ-cyclodextrin and potassium hydroxide in water to obtain a mixed solution, wherein the feeding ratio of γ-cyclodextrin:potassium hydroxide:water is 3g:1g:100mL; filter the mixed solution through a 0.45μm organic filter membrane into a glass tube, then place the glass tube in a beaker containing methanol, seal the beaker and place it in a 60℃ water bath to allow methanol vapor to diffuse into the solution in the reaction vessel for 3 hours; after the reaction is completed, take out the supernatant, add an 8mg / mL hexadecyltrimethylammonium bromide aqueous solution and methanol to the supernatant to trigger rapid precipitation of the crystalline substance, wherein the volume ratio of hexadecyltrimethylammonium bromide aqueous solution:supernatant is 10mL:100mL, and the volume ratio of methanol:supernatant is 100mL:100mL; incubate the resulting suspension at room temperature for 3 hours, centrifuge to collect the precipitate, wash the collected precipitate with methanol, and then vacuum dry it at 50℃ for 12 hours to obtain crystalline γ-CD-MOF;

[0059] c) Add a 2.5 mg / mL minoxidil ethanol solution to the reaction vessel, then add purified illite and γ-CD-MOF to the minoxidil ethanol solution. The ratio of illite:γ-CD-MOF:minoxidil ethanol solution is 2 g:4 g:200 mL. After the addition is complete, stir the mixture at 30 °C for 3 hours to stop the reaction. Centrifuge the product and vacuum dry it at 50 °C for 12 hours to obtain the illite@γ-CD-MOF composite drug-loaded material.

[0060] The illite@γ-CD-MOF composite drug-loaded material prepared in this embodiment was adhered to a conductive adhesive, sputter-coated with gold, and the appearance of the sample was observed using a TESCAN MIRA LMS scanning electron microscope. The test results... Figure 1 As shown.

[0061] Figure 1 Here is a scanning electron microscope (SEM) image of the illite@γ-CD-MOF composite drug-loaded material prepared in this embodiment; Figure 1 As can be seen, the microstructure of the illite@γ-CD-MOF composite drug-loaded material exhibits an irregular cubic shape. Some of the drug is adsorbed into the pores of γ-CD-MOF, some into the interlayer spacing of illite, and some remains on the surface of the illite@γ-CD-MOF composite material. Therefore, the illite@γ-CD-MOF composite material prepared by this invention has a good appearance and excellent drug loading capacity.

[0062] The drug loading capacity of the illite@γ-CD-MOF composite drug-loaded material prepared in this embodiment for minoxidil was tested using an ultraviolet spectrophotometer. The test results are shown in Table 1.

[0063] II. Preparation of illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film:

[0064] First, PVA is dissolved in water at 80℃ to obtain a 10wt% PVA aqueous solution. Then, illite@γ-CD-MOF composite drug-loaded material (5wt% of PVA) is added to the PVA aqueous solution and stirred to mix evenly. The mixture is then ultrasonically degassed at room temperature for 30 minutes. Finally, it is poured into a mold and air-dried to obtain an illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film.

[0065] Example 4

[0066] I. Preparation of illite@γ-CD-MOF composite drug delivery material:

[0067] a) First, put the raw illite powder into a crucible, then place the crucible containing the raw illite powder into a muffle furnace, heat it to 300°C at a heating rate of 10°C / min, calcine for 3 hours, and then cool it naturally to room temperature to obtain the illite after high-temperature calcination.

[0068] b) Dissolve γ-cyclodextrin and potassium hydroxide in water to obtain a mixed solution, wherein the feeding ratio of γ-cyclodextrin:potassium hydroxide:water is 3g:1g:100mL; filter the mixed solution through a 0.45μm organic filter membrane into a glass tube, then place the glass tube in a beaker containing methanol, seal the beaker and place it in a 60℃ water bath to allow methanol vapor to diffuse into the solution in the reaction vessel for 3 hours; after the reaction is completed, take out the supernatant, add an 8mg / mL hexadecyltrimethylammonium bromide aqueous solution and methanol to the supernatant to trigger rapid precipitation of the crystalline substance, wherein the volume ratio of hexadecyltrimethylammonium bromide aqueous solution:supernatant is 10mL:100mL, and the volume ratio of methanol:supernatant is 100mL:100mL; incubate the resulting suspension at room temperature for 3 hours, centrifuge to collect the precipitate, wash the collected precipitate with methanol, and then vacuum dry it at 50℃ for 12 hours to obtain crystalline γ-CD-MOF;

[0069] c) Add a 2.5 mg / mL minoxidil ethanol solution to the reaction vessel, and add purified illite and γ-CD-MOF to the minoxidil ethanol solution. The addition ratio of illite:γ-CD-MOF:minoxidil ethanol solution is 4 g:2 g:200 ml. After the addition is complete, the mixture is stirred at 30 °C for 3 hours to stop the reaction. The resulting product is then centrifuged and dried under vacuum at 50 °C for 12 hours to obtain the illite@γ-CD-MOF composite drug-loaded material.

[0070] The drug loading capacity of the illite@γ-CD-MOF composite drug-loaded material prepared in this embodiment for minoxidil was tested using an ultraviolet spectrophotometer. The test results are shown in Table 1.

[0071] II. Preparation of illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film:

[0072] First, PVA is dissolved in water at 80℃ to obtain a 10wt% PVA aqueous solution. Then, illite@γ-CD-MOF composite drug-loaded material (5wt% of PVA) is added to the PVA aqueous solution and stirred to mix evenly. The mixture is then ultrasonically degassed at room temperature for 30 minutes. Finally, it is poured into a mold and air-dried to obtain an illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film.

[0073] Comparative Example 1

[0074] I. Preparation of γ-CD-MOF drug-loaded materials

[0075] a) Dissolve γ-cyclodextrin and potassium hydroxide in water to obtain a mixed solution, wherein the feeding ratio of γ-cyclodextrin:potassium hydroxide:water is 3g:1g:100mL; filter the mixed solution through a 0.45μm organic filter membrane into a glass tube, then place the glass tube in a beaker containing methanol, seal the beaker and place it in a 60℃ water bath to allow methanol vapor to diffuse into the solution in the reaction vessel for 3 hours; after the reaction is completed, take out the supernatant, add an 8mg / mL hexadecyltrimethylammonium bromide aqueous solution and methanol to the supernatant to trigger rapid precipitation of the crystalline substance, wherein the volume ratio of hexadecyltrimethylammonium bromide aqueous solution:supernatant is 10mL:100mL, and the volume ratio of methanol:supernatant is 100mL:100mL; incubate the resulting suspension at room temperature for 3 hours, centrifuge to collect the precipitate, wash the collected precipitate with methanol, and then vacuum dry at 50℃ for 12 hours to obtain crystalline γ-CD-MOF;

[0076] b) Add γ-CD-MOF and a 2.5 mg / mL minoxidil ethanol solution to a reaction vessel, wherein the ratio of γ-CD-MOF to minoxidil ethanol solution is 6 g: 200 mL. After the addition is complete, the mixture is stirred at 30 °C for 6 hours to stop the reaction. The resulting product is then centrifuged and dried under vacuum at 50 °C for 12 hours to obtain the γ-CD-MOF drug-loaded material.

[0077] The loading capacity of minoxidil on the γ-CD-MOF drug-loaded material prepared in this comparative example was tested using an ultraviolet spectrophotometer. The test results are shown in Table 1.

[0078] II. Preparation of γ-CD-MOF drug-loaded material / PVA composite drug-loaded film

[0079] First, PVA is dissolved in water at 80℃ to obtain a 10wt% PVA aqueous solution. Then, γ-CD-MOF drug-loaded material (the amount of γ-CD-MOF drug-loaded material added is 5wt% of PVA) is added to the PVA aqueous solution and stirred to mix evenly. Then, it is ultrasonically degassed at room temperature for 30 minutes. Finally, it is poured into a mold and air-dried to obtain a γ-CD-MOF drug-loaded material / PVA composite drug-loaded film.

[0080] Comparative Example 2

[0081] I. Preparation of illite drug-loaded materials

[0082] a) Add the raw illite powder to water, first ultrasonically disperse for 30 minutes, then magnetically stir to make it evenly dispersed in the water. The ratio of raw illite powder to water is 20g:400mL. Then let it stand for 8 hours, discard the supernatant, and separate the remaining material (intermediate suspension and bottom impurities) into solid and liquid by centrifugation. After centrifugation and washing, the separated solid is dried at 100℃. The dried solid is ground into fine powder using a mortar and pestle to obtain the purified illite.

[0083] b) The purified illite and a 2 mg / mL minoxidil ethanol solution were added to a reaction vessel, wherein the ratio of illite to minoxidil ethanol solution was 6 g: 200 mL. After the addition was complete, the mixture was stirred at 30 °C for 6 hours to stop the reaction. The product was then centrifuged and dried under vacuum at 50 °C for 12 hours to obtain the illite drug-loaded material.

[0084] The drug loading of minoxidil on the illite-loaded material prepared in this comparative example was tested using an ultraviolet spectrophotometer. The test results are shown in Table 1.

[0085] II. Preparation of illite-loaded drug-loaded materials / PVA composite drug-loaded films

[0086] First, PVA is dissolved in water at 80℃ to obtain a 10wt% PVA aqueous solution. Then, illite drug-loaded material (5wt% of PVA) is added to the PVA aqueous solution and stirred to mix evenly. Then, it is ultrasonically degassed at room temperature for 30 minutes. Finally, it is poured into a mold and air-dried to obtain an illite drug-loaded material / PVA composite drug-loaded film.

[0087] Performance testing

[0088] 1) Testing of the drug loading capacity of minoxidil in drug-loaded materials:

[0089] The drug loading of the illite@γ-CD-MOF composite drug-loaded materials prepared in Examples 1-4, the γ-CD-MOF drug-loaded material prepared in Comparative Example 1, and the illite drug-loaded material prepared in Comparative Example 2 were tested, and the test results are shown in Table 1.

[0090] Table 1. Drug loading of drug-loaded materials prepared in the examples and comparative examples.

[0091] Test Project Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Comparative Example 2 Drug loading (mg / g) 246.20 241.00 253.14 242.75 238.72 191.79

[0092] As shown in Table 1, the illite@γ-CD-MOF composite drug-loaded material prepared in this invention has a higher drug loading capacity for minoxidil compared with γ-CD-MOF drug-loaded materials and illite drug-loaded materials.

[0093] 2) Test of potassium ion release rate of drug-loaded material:

[0094] The potassium ion release rate (based on the concentration of released potassium ions) of the illite@γ-CD-MOF composite drug-loaded material prepared in Example 3, the γ-CD-MOF drug-loaded material prepared in Comparative Example 1, and the illite drug-loaded material prepared in Comparative Example 2 were tested, and the test results are shown in Table 2.

[0095] Table 2. Potassium ion release rate of drug-loaded materials prepared in the examples and comparative examples.

[0096] Test Project Example 3 Comparative Example 1 Comparative Example 2 Potassium ion concentration (mg / L) 2.425 2.320 0.699

[0097] As shown in Table 2, the illite@γ-CD-MOF composite drug-loaded material prepared in this invention has a higher potassium ion release rate compared with γ-CD-MOF drug-loaded materials and illite drug-loaded materials. When used as a drug-loaded material for minoxidil, it will release more potassium ions that are beneficial to hair growth while releasing the drug, which can further enhance the effect of minoxidil in treating hair loss.

[0098] 3) Testing the drug release performance of the drug-loaded film:

[0099] The drug release performance of the illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film prepared in Example 3, the γ-CD-MOF drug-loaded material / PVA composite drug-loaded film prepared in Comparative Example 1, and the illite drug-loaded material / PVA composite drug-loaded film prepared in Comparative Example 2 were tested, and the test results are as follows: Figure 2 , Figure 3 and Figure 4 As shown.

[0100] Figure 2 The drug release curve of the illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film prepared in Example 3 is shown. Figure 3 The drug release curve of the γ-CD-MOF drug-loaded material / PVA composite drug-loaded film prepared in Comparative Example 1 is shown. Figure 4 The drug release curves of the illite drug-loaded material / PVA composite drug-loaded film prepared in Comparative Example 2 are shown. Figures 2 to 4 As can be seen, the drugs in the drug-loaded films are released slowly and can be completely released within about 8 hours. The highest cumulative release amounts are 37.3%, 36.4%, and 35.7%, respectively. Therefore, the illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film prepared in this invention has a better drug release amount compared with the γ-CD-MOF drug-loaded material / PVA composite drug-loaded film and the illite drug-loaded material / PVA composite drug-loaded film.

[0101] Finally, it should be noted that the above are only some preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-essential improvements and adjustments made by those skilled in the art based on the above content of the present invention shall fall within the scope of protection of the present invention.

Claims

1. A illite γ-CD-MOF composite drug-loaded material, characterized in that: is obtained by reacting illite, γ-CD-MOF and minoxidil ethanol solution, and the γ-CD-MOF is obtained by reacting γ-cyclodextrin and water-soluble potassium salt by a vapor diffusion method, wherein the molar ratio of γ-cyclodextrin to water-soluble potassium salt is 1: (6-12).

2. The illite γ-CD-MOF composite drug-loaded material according to claim 1, characterized in that: The illite is illite purified by a gravity separation method or illite calcined at high temperature.

3. The illite γ-CD-MOF composite drug-loaded material according to claim 2, characterized in that, The illite purified by the gravity separation method comprises the following steps: The raw illite powder is uniformly dispersed in water, and after standing for 6-10 hours, the supernatant is discarded, and the remaining solid is separated by a centrifugal machine. The separated solid is washed by centrifugation and dried at 90-110℃ to obtain the purified illite.

4. The illite γ-CD-MOF composite drug-loaded material according to claim 2, characterized in that, The illite calcined at high temperature comprises the following steps: The raw illite powder is placed in a muffle furnace and heated to 300-800℃ at a heating rate of 5-10℃ / min, and after calcination for 3-8 hours, it is naturally cooled to room temperature to obtain the illite calcined at high temperature.

5. The illite γ-CD-MOF composite drug-loaded material according to claim 1, characterized in that, The γ-CD-MOF prepared by the vapor diffusion method comprises the following steps: The γ-cyclodextrin and water-soluble potassium salt are dissolved in water to obtain a mixed solution, the mixed solution is filtered through a filter membrane into a reaction container, and then the reaction container is placed in a methanol vapor atmosphere, and methanol vapor is diffused into the solution for 3-8 hours. After the supernatant is taken out, cetyltrimethylammonium bromide and methanol are added to the supernatant to obtain a suspension, which is incubated at room temperature for 3-8 hours, and then the precipitate is collected by centrifugation. The collected precipitate is washed with methanol and vacuum dried at 40-60℃ for 8-12 hours to obtain crystalline γ-CD-MOF.

6. A method of preparing the illite γ-CD-MOF composite drug-loaded material of claim 1, characterized in that, The following steps are included: The illite, γ-CD-MOF and minoxidil ethanol solution are stirred and reacted at 20-60℃ for 1-9 hours, and after the reaction is completed, the solid product is collected to obtain the illite@γ-CD-MOF composite drug-loaded material.

7. Use of the illite γ-CD-MOF composite drug-loaded material according to claim 1, characterized in that: The illite@γ-CD-MOF composite drug-loaded material is blended with PVA into a film with water as the solvent to prepare the illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film.

8. Use according to claim 7, characterized in that, The preparation of the illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film comprises the following steps: First, PVA is dissolved in water to obtain a PVA aqueous solution, then illite@γ-CD-MOF composite drug-loaded material is added to the PVA aqueous solution, stirred to mix uniformly, ultrasonically defoamed for 10-30 minutes, and finally poured into a mold and naturally air dried to obtain the illite@γ-CD-MOF composite drug-loaded material / PVA composite drug-loaded film.

9. Use according to claim 8, characterized in that: The addition amount of the illite@γ-CD-MOF composite drug-loaded material is 1-9 wt% of PVA.

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