Drug-loaded artificial pericardium and preparation method thereof

Abstract

The present invention relates to the field of medical material technology, and in particular to a drug-loaded artificial pericardium and a preparation method thereof. The drug-loaded artificial pericardium provided by the invention can be used to reduce adhesion between the heart and surrounding tissues and reduce postoperative inflammatory reactions and fibrosis after cardiac surgery, and has good biosafety; in addition, according to drug concentration detection, it is proved that the film has the effect of sustained drug release, and can maintain a relative drug concentration for a period of time after surgery, reducing inflammatory reactions and fibrosis. The film of the present invention also has good water reactivity and biodegradability. After being moistened, it can rely on intermolecular forces to completely adhere to cardiac tissue, and does not rely on viscosity to adhere to the heart, avoiding secondary damage to the tissue caused by tearing again, and can be completely degraded within a certain period of time after being implanted in a living body. In addition, compared with traditional anti-adhesion flushing solutions, this film can be cut as needed and attached to the required part to avoid the impact of excessive flushing on other tissues.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, and in particular to a drug-loaded artificial pericardium and a preparation method thereof. Background Art

[0002] In recent years, with the continuous advancement of cardiac surgical technology, the rate of secondary surgeries has gradually increased, and adhesions have become a major factor affecting the effectiveness of secondary surgeries. For example, during coronary artery bypass grafting, adhesions can significantly increase the incidence of severe bleeding-related complications.

[0003] Currently, anti-adhesion materials can be divided into two categories: non-absorbable materials and bioabsorbable materials. Non-absorbable materials include synthetic membranes and xenograft membranes. Synthetic membranes include silicone rubber, expanded polytetrafluoroethylene membranes, polyethylene films, and polyester mesh. Bioabsorbable materials include polylactic acid, carboxymethyl cellulose, and hyaluronic acid films.

[0004] Current non-absorbable materials used as anti-adhesion materials act as permanent foreign bodies in the body and may cause inflammatory reactions. Single films designed to prevent cardiac adhesions only provide isolation and are ineffective in promoting tissue healing, reducing myocardial fibrosis and inflammation, or improving cardiac function recovery. Furthermore, current postoperative adhesion prevention gels or films cannot be cut and applied as needed. Once adhered to the heart, the film is difficult to remove, potentially causing secondary tissue damage.

[0005] Chinese patent CN201711425189 discloses an absorbable anti-adhesion material and a membrane prepared therefrom for use after cardiac surgery. The isolation film is made of chitosan, gelatin, glycerol, collagen, and silk fibroin, has good biocompatibility and is absorbable and degradable. It can prevent adhesion between the heart and surrounding tissues after surgery and protect heart function. However, this anti-adhesion membrane can only physically prevent adhesions and does not have anti-inflammatory and antioxidant capabilities.

[0006] Chinese patent CN201310214708.2 discloses a wound irrigation and anti-adhesion fluid for surgical operations, as well as its preparation method and application. The fluid uses sodium carboxymethyl cellulose, brown algal oligosaccharides, hydroxyethyl starch, polyethylene glycol, and sodium chloride, which are mixed with injection water by stirring or cross-linking to form a film or liquid with multiple functions such as hemostasis, antibacterial, anti-adhesion, and healing promotion. However, this anti-adhesion irrigation fluid cannot be used to irrigate specific areas as needed, may affect areas outside the surgical area, and does not have anti-inflammatory and antioxidant capabilities.

[0007] In view of this, the present invention is proposed. Summary of the Invention

[0008] In order to solve the above technical problems, the present invention provides an artificial pericardium that can prevent postoperative tissue adhesion and alleviate cardiac fibrosis and inflammatory response.

[0009] Specifically, the technical solution of the present invention is as follows:

[0010] In a first aspect, the present invention provides a drug-loaded artificial pericardium, which is prepared from the following raw materials in parts by weight: 0.575-0.625 parts of polyethylene oxide (PEO), 0.09-0.11 parts of polyethylene glycol (PEG), 0.9-1.1 parts of α-cyclodextrin (α-CD), 0.160-0.240 parts of sodium carboxymethyl cellulose (NaCMC), and 0.005-0.015 parts of colchicine.

[0011] The materials used in the drug-loaded artificial pericardium provided by the present invention are all absorbable materials with good biocompatibility, are not easy to cause inflammatory reactions in the body, and can be degraded and absorbed; they can promote the recovery of the heart to a certain extent through a sustained release effect, and have a better effect on promoting tissue healing, reducing myocardial fibrosis and inflammatory reactions, and improving cardiac function recovery; they can also be cut as needed and attached to specific parts of the heart. After being moistened with water, they can completely wrap the heart without causing contusion to the tissue.

[0012] Preferably, the drug-loaded artificial pericardium is prepared from the following raw materials in parts by weight: 0.600 parts of polyethylene oxide, 0.1 parts of polyethylene glycol, 1.0 parts of α-cyclodextrin, 0.200 parts of sodium carboxymethyl cellulose, and 0.01 parts of colchicine.

[0013] Preferably, the molecular weight of polyethylene oxide is 1×10 6 -3×10 6 .

[0014] Preferably, the molecular weight of polyethylene glycol is 1500-2500.

[0015] In a second aspect, the present invention provides a method for preparing the drug-loaded artificial pericardium described in the first aspect, comprising the following steps: adding α-cyclodextrin to a polyethylene glycol aqueous solution at 50-70°C and mixing; then successively adding a polyethylene oxide aqueous solution and colchicine and mixing; after drying at 50-70°C for 12-24 hours, adding a sodium carboxymethyl cellulose aqueous solution to the surface of the mixture and continuing to dry at 50-70°C for 12-24 hours.

[0016] The present invention uses α-cyclodextrin, polyethylene glycol, and polyethylene oxide as main materials for preparing a device for preventing postoperative cardiac adhesion. The device has good water reactivity and complete tissue wrapping properties and can be tailored as needed. The present invention uses colchicine as a drug loaded on the artificial pericardium, which can slowly release the drug efficacy through the film to reduce the degree of cardiac fibrosis and inflammatory response. The present invention prepares a double-layer artificial pericardium, uses NaCMC as the outer physical isolation layer to prevent adhesion between the heart and surrounding tissues, and releases drugs in the inner layer to promote cardiac function recovery.

[0017] Preferably, the mass fraction of the polyethylene oxide aqueous solution is 3.5%-4.5%.

[0018] Preferably, the mass fraction of the polyethylene glycol aqueous solution is 1.5%-2.5%.

[0019] Preferably, the mass fraction of the sodium carboxymethyl cellulose aqueous solution is 1.6%-2.4%.

[0020] More preferably, the preparation method comprises the following steps: adding 0.575-0.625 parts by mass of a molecule having a molecular weight of 1×10 6 -3×10 6 The polyethylene oxide is dissolved in 14-16 parts by volume of ultrapure water to prepare a polyethylene oxide aqueous solution with a mass fraction of 3.5%-4.5%; 0.09-0.11 parts by mass of polyethylene glycol with a molecular weight of 1500-2500 is dissolved in 4-6 parts by volume of ultrapure water, vortexed and mixed, and then 0.9-1.1 parts by mass of α-cyclodextrin is slowly added in a 55-65°C water bath to dissolve, and ultrasonicated in 55-65°C water bath for 50-70s to obtain a mixture of polyethylene oxide and α-cyclodextrin; then 14-16 parts by volume of a polyethylene oxide aqueous solution with a mass fraction of 3.5%-4.5% is added to prepare α - a mixed solution of cyclodextrin, polyethylene oxide, and polyethylene glycol; then adding 0.005-0.015 parts by mass of colchicine, and centrifuging and stirring for 1.5-2.5 minutes using a mixing and degassing machine at 1500-2500 rpm, repeating 2-4 times to obtain a thick mixture; adding the thick mixture to a glass-bottomed culture dish, sealing it in a 55-65°C oven overnight to remove bubbles in the mixture; then adding 4-6 parts by volume of a 1.6%-2.4% sodium carboxymethyl cellulose solution to the surface of the mixture, and drying it in a 55-65°C oven overnight; wherein the ratio of the parts by mass to the parts by volume is g:mL.

[0021] The preparation method provided by the present invention is simple, and the prepared drug-loaded artificial pericardium has good biocompatibility, is absorbable and degradable, is convenient to implement (water-responsive and can be trimmed on demand), and can alleviate cardiac fibrosis and inflammatory response.

[0022] Beneficial effects:

[0023] The present invention provides a drug-loaded artificial pericardium and a preparation method thereof. The drug-loaded artificial pericardium provided by the present invention can be used to reduce adhesion between the heart and surrounding tissues and reduce postoperative inflammatory reactions and the degree of fibrosis after cardiac surgery. By comparing the experimental group and the control group 28 days after simulating myocardial infarction in an animal experiment, it was found that the film of the present invention has the effect of reducing cardiac adhesion, and according to in vitro cell experiments, the biosafety of the film and the ability of the anti-adhesion layer to resist fibroblast adhesion were proved. In addition, according to drug concentration detection, it was proved that the film has the effect of sustained drug release, can maintain a relative drug concentration for a period of time after surgery, and reduce inflammatory reactions and the degree of fibrosis. The film of the present invention also has good water reactivity and biodegradability. After being wetted, it can rely on intermolecular forces to completely adhere to the heart tissue, and does not rely on viscosity to adhere to the heart, avoiding secondary damage to the tissue caused by tearing again, and can be completely degraded within a certain period of time after implantation in the organism. In addition, compared with traditional anti-adhesion flushing solutions, this film can be cut as needed and attached to the required part to avoid the impact of excessive flushing on other tissues. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the technical solutions of the present invention or the prior art, the drawings required for use in the embodiments or the description of the prior art will be described below.

[0025] Figure 1 This is the anti-adhesion result of the artificial pericardium in Experimental Example 1 of the present invention.

[0026] Figure 2 This is the drug release curve of the artificial pericardium in Experimental Example 1 of the present invention.

[0027] Figure 3 This is an electron microscope image of the artificial pericardium in Experimental Example 1 of the present invention.

[0028] Figure 4 This is the water reactivity result of the artificial pericardium in Experimental Example 1 of the present invention.

[0029] Figure 5 This is the biosafety result of the artificial pericardium in Experimental Example 1 of the present invention.

[0030] Figure 6 This is the degradability result of the artificial pericardium in Experimental Example 1 of the invention.

[0031] Figure 7 This is the manufacturing process and actual picture of the artificial pericardium of the present invention. DETAILED DESCRIPTION

[0032] In order to prevent tissue adhesion after cardiac surgery, the present invention provides an artificial pericardium with good biocompatibility, absorbable and degradable properties, convenient implementation (water responsiveness and trimmability on demand), and the ability to reduce cardiac fibrosis and inflammatory response.

[0033] The present invention adopts the following technical solutions:

[0034] An artificial pericardium is designed to prevent postoperative tissue adhesion and alleviate cardiac fibrosis and inflammatory reactions. The membrane is made from the following ingredients: α-cyclodextrin (α-CD), polyethylene glycol (PEG), polyethylene oxide (PEO), sodium carboxymethylcellulose (NaCMC), and colchicine. All ingredients are biodegradable and absorbable, exhibiting excellent biocompatibility and preventing autoinflammatory reactions.

[0035] The artificial pericardium provided by the present invention uses α-CD, PEG, and PEO as the main materials for preparing the inner layer of the film, wherein α-CD and PEG serve as the skeleton part of the film, and PEO serves as the cross-linking part of the film. After preparation, the film can be cut as needed and has good water reactivity. After being wetted by water, the film can shrink and completely wrap the attached tissue, and will not cause contusion to the tissue after being uncovered.

[0036] The artificial pericardium provided by this invention uses NaCMC as the outer layer of the membrane. NaCMC provides a physical barrier to tissue, preventing fibrin produced by surrounding tissue from adhering to the heart, effectively preventing postoperative cardiac adhesions. NaCMC also exhibits excellent biocompatibility with tissue and does not induce autoinflammatory reactions.

[0037] In one of the more specific and preferred embodiments provided by the present invention, the preparation method is: 0.600g of a molecule with a molecular weight of 2×10 6 Dissolve 15 mL of PEO in 15 mL of ultrapure water to prepare a 4% PEO solution. Dissolve 0.1 g of PEG (molecular weight: 2000) in 5 mL of ultrapure water. Vortex and mix thoroughly. Slowly add 1 g of α-CD to dissolve in a 60°C water bath. Ultrasonicate in a 60°C water bath for 1 minute to obtain a PEG-α-CD mixture. Add 15 mL of a 4% PEO solution to create an α-CD / PEG / PEO solution. Add 10 mg of colchicine and centrifuge at 2000 rpm for 2 minutes using a mixing degassing machine. Repeat twice. The resulting thick mixture is added to a glass-bottomed culture dish and sealed in a 60°C oven overnight (12 hours) to remove air bubbles. Then, add 10 mL of a 2% NaCMC solution to the surface of the mixture and dry in a 60°C oven overnight (12 hours) to obtain the final drug-loaded artificial pericardium.

[0038] The artificial pericardium provided by the present invention uses colchicine as the drug loaded in the inner layer of the film, which can effectively reduce the degree and area of ​​cardiac fibrosis after surgery or myocardial infarction, help restore cardiac function, and also help reduce cardiac inflammatory response and reduce adhesion between the heart and surrounding tissues after surgery.

[0039] To make the objectives, technical solutions, and advantages of the present invention more clear, the technical solutions of the present invention are described clearly and completely below. Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. All other embodiments derived by persons of ordinary skill in the art based on the embodiments of the present invention without inventive effort are also within the scope of protection of the present invention.

[0040] The endpoints and any values ​​of the ranges disclosed in this specification are not limited to the exact ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be considered to be specifically disclosed herein.

[0041] In the description of this specification, the reference terms "one embodiment", "some embodiments", "specific implementation methods", or "some specific implementation methods" and the like mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the embodiments of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and features of different embodiments or examples without contradiction.

[0042] In the examples provided herein, if specific techniques or conditions are not specified, the experiments were performed according to those described in literature in the field or according to the product instructions. Reagents or instruments used without manufacturer specified are conventional products available through regular channels.

[0043] Example 1

[0044] This embodiment provides a drug-loaded artificial pericardium that can prevent postoperative tissue adhesion and alleviate cardiac fibrosis and inflammatory response. The preparation method thereof is as follows:

[0045] 0.600g of molecular weight is 2×10 6Dissolve 100 mL of PEO in 15 mL of ultrapure water to prepare a 4% PEO solution. Dissolve 0.1 g of PEG (molecular weight: 2000) in 5 mL of ultrapure water. Vortex mix thoroughly, then slowly add 1 g of α-CD to dissolve in a 60°C water bath. Ultrasonicate in the 60°C water bath for 1 minute to obtain a PEG-α-CD mixture. Add 15 mL of a 4% PEO solution to create an α-CD / PEG / PEO solution. Add 10 mg of colchicine and centrifuge at 2000 rpm for 2 minutes using a mixer / degasser. Repeat twice. The resulting thick mixture is placed in a glass-bottomed Petri dish, sealed, and placed in a 60°C oven overnight (12 hours) to remove air bubbles. Then, add 10 mL of a 2% NaCMC solution to the surface of the mixture, which is then dried in a 60°C oven overnight (12 hours) to obtain the final drug-loaded artificial pericardium.

[0046] Example 2

[0047] This embodiment provides a drug-loaded artificial pericardium that can prevent postoperative tissue adhesion and alleviate cardiac fibrosis and inflammatory response. The preparation method thereof is as follows:

[0048] 0.625g molecular weight is 3×10 6 Dissolve 16 mL of PEO in 16 mL of ultrapure water to prepare a 3.9% PEO solution. Dissolve 0.11 g of PEG (molecular weight: 2000) in 5.5 mL of ultrapure water. Vortex mix thoroughly, then slowly add 1.1 g of α-CD in a 65°C water bath. Ultrasonicate in the water at 65°C for 1 minute to obtain a PEG-α-CD mixture. Add 16 mL of a 3.9% PEO solution to create an α-CD / PEG / PEO solution. Add 10 mg of colchicine, and centrifuge at 2000 rpm for 2 minutes using a mixer / degasser. Repeat three times. The resulting thick mixture is placed in a glass-bottomed Petri dish, sealed, and placed in a 65°C oven overnight (12 hours) to remove air bubbles. Then, add 10 mL of a 2% NaCMC solution to the surface of the mixture, which is then dried in a 65°C oven overnight (12 hours) to obtain the final drug-loaded artificial pericardium.

[0049] Example 3

[0050] This embodiment provides a drug-loaded artificial pericardium that can prevent postoperative tissue adhesion and alleviate cardiac fibrosis and inflammatory response. The preparation method thereof is as follows:

[0051] 0.575g of molecular weight is 2×10 6Dissolve 14 mL of PEO in 14 mL of ultrapure water to prepare a 4.1% PEO solution. Dissolve 0.09 g of PEG (molecular weight: 2000) in 4.5 mL of ultrapure water. Vortex mix thoroughly, then slowly add 0.9 g of α-CD in a 60°C water bath. Ultrasonicate in 55°C water for 1 minute to obtain a PEG-α-CD mixture. Then, add 14 mL of a 4.1% PEO solution to create an α-CD / PEG / PEO solution. Then, add 10 mg of colchicine. Centrifuge at 2000 rpm for 2 minutes using a mixer / degasser, repeat three times. The resulting thick mixture is placed in a glass-bottomed Petri dish, sealed, and placed in a 55°C oven overnight (12 hours) to remove air bubbles. Then, add 10 mL of a 2% NaCMC solution to the surface of the mixture, and dry in a 55°C oven overnight (12 hours) to obtain the final drug-loaded artificial pericardium.

[0052] Experimental Example 1

[0053] In this experimental example, the drug-loaded artificial pericardium prepared in Example 1 was used as the experimental material to test its anti-adhesion ability, drug release concentration, microstructure, water reaction characteristics, biosafety, and degradability.

[0054] The specific detection methods are as follows:

[0055] Anti-adhesion ability: A myocardial infarction model was established by ligating the anterior descending branch of the mouse coronary artery. A cut artificial pericardium patch was implanted in the ligated area. 28 days after implantation, the patch was photographed and compared with the non-implanted group to observe the adhesion effect between the heart and surrounding tissues.

[0056] Drug Release Concentration: The artificial pericardium was placed in a 24-well Transwell chamber with the drug-loaded layer facing downward, simulating drug release from the artificial pericardium attached to the cardiac surface. Ultrapure water was added to the lower well of the chamber, and the absorbance of the solution in the well was measured every 1, 2, 3, and 4 days. A colchicine standard concentration reagent was prepared and its absorbance was measured to generate a colchicine absorbance-concentration standard curve. The measured absorbances were substituted into the curve to determine the drug release concentration at different days, and the drug release curve was plotted.

[0057] Microstructure: A 1 mm x 1 mm piece of artificial pericardium was attached to a sample carrier with conductive tape, and its microscopic double-layer film structure was observed using a scanning electron microscope.

[0058] Water reaction characteristics: The prepared artificial pericardium was cut into a 1 cm x 0.5 cm rectangle and placed in a culture dish filled with ultrapure water. The reaction of the film after contact with water was observed within an hour.

[0059] Biosafety: Primary mouse fibroblasts were transplanted onto 6-well plates containing artificial pericardium and 6-well plates without artificial pericardium to form experimental and control groups, respectively. The cells were immunofluorescently stained with F-actin and DAPI to observe cell growth status.

[0060] Degradability: Artificial pericardium was implanted on the surface of mouse heart, and the thorax was opened 7 days later to observe the degradation of the artificial pericardium.

[0061] Test results are shown in Figure 1-6 .

[0062] Depend on Figure 1 It can be seen that the adhesion between the heart and surrounding tissues in the experimental group implanted with artificial pericardium was less severe than that in the control group without treatment.

[0063] Depend on Figure 2 It can be seen that the drug concentration of the drug-loaded artificial pericardium gradually reached equilibrium within 4 days, indicating the drug sustained-release effect of the film.

[0064] Depend on Figure 3 It can be seen that the artificial pericardium has a double-layer structure under a scanning electron microscope. The drug-loading layer has a relatively loose structure, which is conducive to drug release, and the anti-adhesion layer has a dense structure, which can prevent drug release and ensure the directional release of colchicine to a certain extent.

[0065] Depend on Figure 4 It can be seen that the artificial pericardium reacts quickly to water and shrinks within 2 seconds, which shows that the film has rapid water responsiveness and can quickly adhere to the tissue on the moist heart surface.

[0066] Depend on Figure 5 It can be seen that cells grow well on the artificial pericardium, and compared with the control group, fewer cardiac fibroblasts adhere to the artificial pericardium, indicating that the film's anti-fibroblast adhesion ability reflects its anti-adhesion property.

[0067] Depend on Figure 6 It can be seen that 7 days after the artificial pericardium was implanted on the surface of the heart, most of the film was degraded, proving its degradability.

[0068] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A drug-loaded artificial pericardium, characterized in that: The drug-loaded artificial pericardium is prepared from the following raw materials in parts by weight: 0.575-0.625 parts of polyethylene oxide, 0.09-0.11 parts of polyethylene glycol, 0.9-1.1 parts of α-cyclodextrin, 0.160-0.240 parts of sodium carboxymethyl cellulose, and 0.005-0.015 parts of colchicine. The drug-loaded artificial pericardium is prepared by the following method: adding α-cyclodextrin to a polyethylene glycol aqueous solution at 50-70°C and mixing; then adding the polyethylene oxide aqueous solution and colchicine in sequence and mixing; drying at 50-70°C for 12-24 hours, adding the sodium carboxymethyl cellulose aqueous solution on the surface of the mixture, and continuing to dry at 50-70°C for 12-24 hours.

2. The drug-loaded artificial pericardium according to claim 1, characterized in that: The preparation method is prepared from the following raw materials in parts by weight: 0.600 parts of polyethylene oxide, 0.1 parts of polyethylene glycol, 1.0 parts of α-cyclodextrin, 0.200 parts of sodium carboxymethyl cellulose, and 0.01 parts of colchicine.

3. The drug-loaded artificial pericardium according to claim 1 or 2, characterized in that: The molecular weight of polyethylene oxide is 1×10 6 -3×10 6 .

4. The drug-loaded artificial pericardium according to claim 1 or 2, characterized in that: The molecular weight of polyethylene glycol is 1500-2500.

5. The drug-loaded artificial pericardium according to claim 3, characterized in that: The molecular weight of polyethylene glycol is 1500-2500.

6. The drug-loaded artificial pericardium according to claim 1, characterized in that: The mass fraction of the polyethylene oxide aqueous solution is 3.5%-4.5%.

7. The drug-loaded artificial pericardium according to claim 1, characterized in that: The mass fraction of the polyethylene glycol aqueous solution is 1.5%-2.5%.

8. The drug-loaded artificial pericardium according to claim 1, characterized in that: The mass fraction of the sodium carboxymethyl cellulose aqueous solution is 1.6%-2.4%.

9. The drug-loaded artificial pericardium according to claim 8, characterized in that: The mass fraction of the sodium carboxymethyl cellulose aqueous solution is 2.0%.

10. The method for preparing the drug-loaded artificial pericardium according to claim 1, characterized in that: The steps include: adding 0.575-0.625 parts by mass of a 1×10 6 -3×10 6 The polyethylene oxide is dissolved in 14-16 parts by volume of ultrapure water to prepare a polyethylene oxide aqueous solution with a mass fraction of 3.5%-4.5%; 0.09-0.11 parts by mass of polyethylene glycol with a molecular weight of 1500-2500 is dissolved in 4-6 parts by volume of ultrapure water, vortexed and mixed, and then 0.9-1.1 parts by mass of α-cyclodextrin is slowly added in a 55-65°C water bath to dissolve, and ultrasonicated in 55-65°C water bath for 50-70s to obtain a mixture of polyethylene oxide and α-cyclodextrin; then 14-16 parts by volume of a polyethylene oxide aqueous solution with a mass fraction of 3.5%-4.5% is added to prepare α - a mixed solution of cyclodextrin, polyethylene oxide, and polyethylene glycol; then adding 0.005-0.015 parts by mass of colchicine, and centrifuging and stirring for 1.5-2.5 minutes using a mixing and degassing machine at 1500-2500 rpm, repeating 2-4 times to obtain a thick mixture; adding the thick mixture to a glass-bottomed culture dish, sealing it in a 55-65°C oven overnight to remove bubbles in the mixture; then adding 4-6 parts by volume of a 1.6%-2.4% sodium carboxymethyl cellulose solution to the surface of the mixture, and drying it in a 55-65°C oven overnight; wherein the ratio of the parts by mass to the parts by volume is g:mL.

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