Double-load core-shell nanofiber membrane as well as preparation method and application thereof
By loading rutin and triptyrene on the dual-loaded core-shell nanofiber membrane and coating polylysine on the surface, the limitations and low bioavailability of traditional drug treatment were solved, and the effective inhibition of inflammation and fibrosis in the target tissue was achieved.
Patent Information
- Application Number
- CN202510113549.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-24
- Publication Date
- 2025-05-13
AI Technical Summary
Traditional drug treatments used to inhibit inflammation and fibrosis have many limitations and side effects, and the bioavailability of local administration methods is extremely low, making it difficult to achieve effective concentrations in target tissues.
Dual-loaded core-shell nanofiber membranes were used to load rutin and triptyrene onto the nanofiber membranes through coaxial electrospinning technology, and polylysine was coated on the surface to improve their apparent solubility and bioavailability.
This achieves increasing the concentration of rutin and triptyrene in the target tissue, significantly reducing the degree of subconjunctival inflammation and fibrosis, and provides an alternative drug formula that continuously administers and reduces the frequency of administration.
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Figure CN119970611A_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the field of bio-nano medical materials and medical intersection technology, and specifically relates to a double-loaded core-shell nanofiber membrane and a preparation method and application thereof. Background Art
[0002] Inflammation and fibrosis are key pathological processes in many diseases. Their occurrence and development can lead to severe damage to tissue structure and function, and have a profound impact on the health of patients. In ocular diseases, subconjunctival injury is a complex and multidimensional challenge, often leading to subconjunctival inflammation. If left untreated, persistent inflammation will further induce subconjunctival fibrosis, which may eventually lead to symblepharon, recurrence of pterygium, and failure of glaucoma filtration surgery, thus seriously affecting vision. However, the pathological development process of inflammation and fibrosis is not only limited to the eye, but also widely exists in various organ and system diseases, such as pulmonary fibrosis, liver fibrosis, renal fibrosis, cardiovascular disease, inflammatory bowel disease, etc., which brings a heavy disease burden to patients. Traditional drug treatments used to inhibit inflammation and fibrosis have many limitations and side effects. For example, although glucocorticoids have a strong anti-inflammatory effect, their long-term use may cause a series of serious side effects such as glaucoma, cataracts, osteoporosis, increased blood sugar, and increased risk of infection, which limits their wide clinical application; although there are many types of conventional non-steroidal anti-inflammatory drugs, some drugs may cause adverse reactions such as gastrointestinal reactions, renal damage, and corneal toxicity; although 5-fluorouracil (5-FU) is often used to inhibit subconjunctival fibrosis, its rapid metabolism and poor dose controllability lead to poor anti-subconjunctival fibrosis effect, and it also faces similar problems in the treatment of fibrosis in other tissues; although mitomycin C used during surgery can inhibit the proliferation of subconjunctival fibroblasts, it is easy to cause corneal epithelial toxicity and scleral dissolution, and its application in other tissues is also limited by cytotoxicity. In addition, the bioavailability of local administration is extremely low. For example, the bioavailability of local eye drops is less than 5%, which makes it difficult for the drug to reach an effective concentration in the target tissue, greatly reducing the therapeutic effect. Therefore, how to overcome drug delivery barriers, increase drug concentration in target tissues, and provide alternative drug formulations for continuous delivery and reduced frequency of delivery has always been a hot topic and difficulty in pharmaceutical research, and is also a key problem that needs to be solved urgently in the medical field.
[0003] Rutin is a flavonoid compound widely found in plants. 27 H 30 O 16, with a molecular weight of 610.52. Rutin has a variety of biological activities, including anti-oxidation, anti-inflammatory, anti-tumor, and inhibition of angiogenesis, showing powerful biological functions. Rutin can reduce inflammatory responses by inhibiting the release of inflammatory mediators and regulating inflammatory signaling pathways. Celastrol is a biologically active monomer extracted from the traditional Chinese medicine Tripterygium wilfordii, with a molecular formula of C 29 H 38 O4, with a molecular weight of 450.61. Studies have shown that tripterygium wilfordii performs well in inhibiting bleomycin-induced pulmonary fibrosis and systemic sclerosis, as well as renal and liver fibrosis in rats. However, despite the strong biological activity of these two natural products, their extremely poor water solubility (the solubility of rutin in water is only 12.5 mg / 100 mL, while tripterygium wilfordii is almost insoluble in water) limits their further application. So far, there have been no reports on the combined use of rutin and tripterygium wilfordii in surgery to inhibit inflammation and fibrosis. Therefore, enhancing the water solubility of these two substances and improving their bioavailability are the primary problems that researchers need to solve. Summary of the invention
[0004] In order to overcome the deficiencies of the prior art, the present invention aims to provide a double-loaded core-shell nanofiber membrane and a preparation method and application thereof.
[0005] To achieve the above purpose, the technical solution adopted by the present invention is as follows: A double-loaded core-shell nanofiber membrane comprises a core-shell nanofiber membrane coated or impregnated with polylysine or chitosan; the core-shell nanofiber membrane is composed of core-shell nanofibers, the shell layer of the core-shell nanofibers is a first degradable biomaterial nanofiber, and the core layer is a second degradable biomaterial nanofiber, the first degradable biomaterial nanofiber is loaded with a drug with anti-inflammatory function, and the second degradable biomaterial nanofiber is loaded with a drug with fibrosis inhibition function.
[0006] Preferably, the first degradable biomaterial and the second degradable biomaterial are the same or different, and the first degradable biomaterial and the second degradable biomaterial are independently one of polylactic acid and zein.
[0007] Preferably, the loading amount of the drug having anti-inflammatory function on the first degradable biomaterial nanofibers is 5-9wt% as a percentage by mass of the first degradable biomaterial nanofibers; and the loading amount of the drug having anti-fibrosis function on the second degradable biomaterial nanofibers is 0.125-0.325wt% as a percentage by mass of the second degradable biomaterial nanofibers.
[0008] Preferably, the drug with anti-inflammatory function and the drug with anti-fibrosis function are both natural drugs.
[0009] Preferably, the drug with anti-inflammatory function is rutin, and the drug with fibrosis inhibition function is tripterygium wilfordii.
[0010] A method for preparing the dual-loaded core-shell nanofiber membrane comprises the following steps: S1. Preparation of shell layer spinning solution and core layer spinning solution: Shell spinning solution: dissolving the first degradable biomaterial and the drug with anti-inflammatory function in the first solvent, stirring evenly, to obtain the shell spinning solution; Core layer spinning solution: dissolving the second degradable biomaterial and the drug having the function of inhibiting fibrosis in the second solvent, stirring evenly, to obtain the core layer spinning solution; S2, coaxial electrospinning: The shell layer spinning solution and the core layer spinning solution are coaxially electrospun and then dried to obtain a core-shell nanofiber membrane; S3, coating or impregnation: The core-shell nanofiber membrane is immersed in a polylysine aqueous solution or a chitosan aqueous solution or the polylysine aqueous solution or the chitosan aqueous solution is sprayed on the core-shell nanofiber membrane and then dried to prepare a dual-loaded core-shell nanofiber membrane.
[0011] Preferably, when the first degradable biomaterial or the second degradable biomaterial is polylactic acid, the corresponding first solvent or the second solvent is chloroform; when the first degradable biomaterial or the second degradable biomaterial is zein, the corresponding first solvent or the second solvent is glacial acetic acid; the concentration of the first degradable biomaterial in the shell spinning solution is 10~14wt%, and the concentration of the second degradable biomaterial in the core spinning solution is 20~25wt%; the concentration of the polylysine aqueous solution or the chitosan aqueous solution is 15~25μg / mL.
[0012] Preferably, the conditions for coaxial electrospinning are: temperature 25~30℃, relative humidity 45~50%, voltage 18~22kV, using a coaxial needle and the shell needle specification is 18G, the core needle specification is 22G, the shell spinning speed is 0.0002~0.0005mm / s, the core spinning speed is 0.0001~0.0003mm / s and the shell spinning speed is greater than the core spinning speed, and the receiving distance is 12~15cm.
[0013] An application of the double-loaded core-shell nanofiber membrane in the preparation of a drug with anti-inflammatory and fibrosis inhibiting functions.
[0014] Preferably, the double-loaded core-shell nanofiber membrane is used in the preparation of a drug for treating subconjunctival lesions.
[0015] Beneficial effects: The present invention adopts coaxial electrospinning technology to make the drug exist in the fiber in an amorphous state, and the prepared core-shell nanofiber has a very high specific surface area, which greatly increases the contact area between the drug and water, and improves the dissolution rate and solubility of the drug in water; the prepared double-loaded core-shell nanofiber membrane is coated with lysine or chitosan on the surface, which can enhance its apparent solubility and reduce the risk of bacterial infection in the early stage of injury, the shell layer is loaded with rutin to achieve early anti-inflammatory effect, and the core layer is loaded with tripterygium wilfordii to achieve late inhibition of fibrosis, ultimately effectively intervening in inflammation and fibrosis during the injury process; at the same time, the obtained double-loaded core-shell nanofiber membrane has good safety. BRIEF DESCRIPTION OF THE DRAWINGS
[0016] Figure 1 : FTIR images (A), water contact angle characterization (B), and XRD patterns (C) of each raw material, dual-loaded core-shell nanofibrous membrane (PRZCE), blank core-shell nanofibrous membrane without lysine coating (PZ), and dual-loaded core-shell nanofibrous membrane without lysine coating (PRZC).
[0017] Figure 2 : TEM images of the dual-loaded core-shell nanofibrous membrane (PRZCE).
[0018] Figure 3 : Representative eye images of rats in the blank core-shell nanofibrous membrane (PZE) group and the blank core-shell nanofibrous membrane without lysine coating (PZ) group 3 to 7 days after surgery.
[0019] Figure 4 : 7 days after surgery, slit lamp photos (A), subconjunctival H&E images (B), and inflammatory cell infiltration statistics (C) of the blank control group (Control), blank core-shell nanofibrous membrane group (PZE), and double-loaded core-shell nanofibrous membrane treatment group (PRZCE).
[0020] Figure 5 : Eight weeks after surgery, slit lamp photographs (A), subconjunctival H&E images (B), Masson staining images (C), inflammatory cell infiltration statistics images (D) and Masson staining statistics images (E) of the blank control group (Control), blank core-shell nanofibrous membrane group (PZE) and double-loaded core-shell nanofibrous membrane treatment group (PRZCE).
[0021] Figure 6 : H&E images of eye tissues in the normal group (Normol), blank control group (Control), blank core-shell nanofibrous membrane group (PZE) and double-loaded core-shell nanofibrous membrane treatment group (PRZCE) 8 weeks after surgery. DETAILED DESCRIPTION
[0022] In order to enable those skilled in the art to better understand the technical solution of the present invention, the present invention is further described below in conjunction with specific embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all the embodiments. Based on the described embodiments, all other embodiments obtained by those skilled in the art without creative work belong to the protection scope of the present invention.
[0023] Example 1
[0024] The preparation method of the dual-loaded core-shell nanofiber membrane (PRZCE) is as follows: S1. Preparation of shell layer spinning solution and core layer spinning solution: Shell spinning solution: polylactic acid and rutin were dissolved in CHCL3 and magnetically stirred for 5 h to obtain a uniform shell spinning solution; in the shell spinning solution, the mass concentration of polylactic acid was 12 wt%, and rutin accounted for 5 wt% of the mass of polylactic acid; Core layer spinning solution: Zein and celastrol were dissolved in glacial acetic acid and stirred with magnetic force for 2 hours to obtain a uniform core layer spinning solution; in the core layer spinning solution, the mass concentration of zein was 25wt%, and celastrol accounted for 0.125wt% of the mass of zein; S2, coaxial electrospinning: The shell layer spinning solution and the core layer spinning solution were coaxially electrospun: the temperature was 30°C, the relative humidity was 45%, the voltage was 22kV, a coaxial needle was used, and the shell layer needle specification was 18G, and the core layer needle specification was 22G; the shell layer spinning speed was 0.0005mm / s, the core layer spinning speed was 0.0003mm / s, the distance between the needle and the collecting plate was 15cm, and then placed in a vacuum drying oven for drying to obtain a core-shell nanofiber membrane; S3, coating or impregnation: A poly-lysine aqueous solution with a concentration of 15 μg / mL was sprayed on the core-shell nanofiber membrane and then dried in a vacuum drying oven to prepare a dual-loaded core-shell nanofiber membrane (PRZCE).
[0025] Comparative Example 1 The preparation method of blank core-shell nanofiber membrane (PZE) is as follows: S1. Preparation of shell layer spinning solution and core layer spinning solution: Shell spinning solution: polylactic acid was dissolved in CHCL3 and magnetically stirred for 5 h to obtain a uniform shell spinning solution; the mass concentration of polylactic acid in the shell spinning solution was 12 wt%; Core layer spinning solution: Zein was dissolved in glacial acetic acid and magnetically stirred for 2 h to obtain a uniform core layer spinning solution; the mass concentration of zein in the core layer spinning solution was 25wt%; S2, coaxial electrospinning: The shell layer spinning solution and the core layer spinning solution were coaxially electrospun: the temperature was 30°C, the relative humidity was 45%, the voltage was 22kV, a coaxial needle was used, and the shell layer needle specification was 18G, and the core layer needle specification was 22G; the shell layer spinning speed was 0.0005mm / s, the core layer spinning speed was 0.0003mm / s, the distance between the needle and the collecting plate was 15cm, and then placed in a vacuum drying oven for drying to obtain a core-shell nanofiber membrane; S3, coating or impregnation: A 15 μg / mL polylysine aqueous solution was sprayed on the core-shell nanofiber membrane, and then dried in a vacuum drying oven to prepare a blank core-shell nanofiber membrane (PZE).
[0026] Comparative Example 2 The method for preparing the blank core-shell nanofiber membrane (PZ) not coated with lysine is different from that of the control example 1 in that step S3 is omitted, and the rest is the same as that of the embodiment 1.
[0027] The product obtained after step S2 is a blank core-shell nanofiber membrane (PZ) not coated with lysine.
[0028] Comparative Example 3 The method for preparing the dual-loaded core-shell nanofiber membrane (PRZC) without lysine coating is different from that of Example 1 in that step S3 is omitted, and the rest is the same as that of Example 1.
[0029] The product obtained after step S2 is a double-loaded core-shell nanofiber membrane (PRZC) not coated with lysine.
[0030] Product structure characterization Figure 1 FTIR images (A), water contact angle characterization (B), and XRD spectra (C) of each raw material, the double-loaded core-shell nanofiber membrane (PRZCE) prepared in Example 1, the blank core-shell nanofiber membrane (PZ) without lysine coating prepared in Control Example 2, and the double-loaded core-shell nanofiber membrane (PRZC) without lysine coating prepared in Control Example 3. In the figure, PLA represents polylactic acid, Zein represents zein, Ru represents rutin, EPL represents polylysine, Cel represents tripterygium wilfordii, PZ represents the blank core-shell nanofiber membrane without lysine coating (prepared in Control Example 2), and PRZC represents the double-loaded core-shell nanofiber membrane without lysine coating (prepared in Control Example 3). FTIR observed: 881cm -1 The characteristic absorption peak at 1300-1200 cm -1 The characteristic absorption peaks appearing near the region (derived from the multiple ring structures in Cel) are 3500cm -1There is an NH vibration absorption peak (derived from the characteristic absorption peak of lysine), indicating that rutin and tripterygium wilfordii have been successfully loaded in the core-shell fiber membrane, and lysine has also been successfully coated on the core-shell fiber membrane. At the same time, the water contact angle changes from 121.8° before polylysine is coated to 59°, proving that PRZCE changes from a hydrophobic membrane to a hydrophilic membrane, which is beneficial to improve the apparent solubility. It can be observed from the XRD spectrum that the diffraction peak of Ru crystalline drugs disappears in PRZCE, indicating that Ru is dispersed in the fiber carrier in an amorphous state during the electrospinning process.
[0031] Figure 2 TEM image of the dual-loaded core-shell nanofiber membrane (PRZCE) prepared in Example 1. The TEM image clearly reveals its unique core-shell structure.
[0032] Performance Testing 1. Animal experiments The subconjunctival injury animal model of SD rats was used to evaluate the inhibitory effects on inflammation and fibrosis. The detailed steps are as follows: The experimental animals were randomly divided into six groups: Normal group (Normol): no treatment including no subconjunctival injury model; Blank control group: a subconjunctival injury model was made, and no implant was placed under the conjunctiva during the operation; Blank core-shell nanofiber membrane (PZE) group: a subconjunctival injury model was prepared, and the blank core-shell nanofiber membrane (PZE) prepared in control example 1 was implanted under the conjunctiva during surgery; Blank core-shell nanofiber membrane (PZE) group': a subconjunctival injury model was made, and the blank core-shell nanofiber membrane (PZE) prepared in control example 1 was implanted under the conjunctiva during surgery; Double-loaded core-shell nanofiber membrane (PRZCE) group: a subconjunctival injury model was prepared, and the double-loaded core-shell nanofiber membrane (PRZCE) prepared in Example 1 was implanted subconjunctivally during surgery; Blank core-shell nanofiber membrane (PZ) not coated with lysine group: A subconjunctival injury model was prepared, and the blank core-shell nanofiber membrane (PZ) not coated with lysine prepared in Control Example 2 was implanted subconjunctivally during surgery.
[0033] The steps of making subconjunctival injury model were as follows: 10% (W / V, g / mL) chloral hydrate solution was intraperitoneally injected into SD rats at a dosage standard of 0.4 mL / 100 g, the eye area was disinfected with iodine, and the conjunctival sac of the operated eye was rinsed with sterile saline after disinfection. 0.5% (15 mL: 75 mg) proparacaine hydrochloride eye drops were used for local anesthesia of the ocular surface. Under a microscope, a 3 mm*6 mm corneal limbal incision was made on the temporal side of the subconjunctival injury, and the corresponding fiber membrane of 1.5 mm*5 mm was implanted under the conjunctiva, and the wound was closed automatically. In the blank control group (Control), the blank core-shell nanofiber membrane (PZE) group, and the double-loaded core-shell nanofiber membrane (PRZCE) group, gatifloxacin eye gel was applied to the conjunctival sac three times a day for seven days to prevent infection. In order to exclude the interference of other anti-infective drugs, the blank core-shell nanofiber membrane (PZE) group and the blank core-shell nanofiber membrane (PZ) group without lysine coating were not coated with gatifloxacin eye gel. All surgeries were performed on the right eye of the animals.
[0034] The animal's operated eyes were observed under the slit lamp after surgery, and the conjunctiva, cornea, anterior chamber and eye conditions were recorded. The observation period was 8 weeks. After the experiment, euthanasia was induced by intraperitoneal injection of overdose anesthesia, and the animal eye specimens were fixed and H&E and Masson staining were performed to evaluate the treatment effect.
[0035] 2. Animal Experiment Results Figure 3 These are representative eye images of rats in the blank core-shell nanofiber membrane (PZE) group and the blank core-shell nanofiber membrane (PZ) group without lysine coating 3 to 7 days after surgery. It can be seen intuitively that compared with the PZ group, the eyeballs of rats in the PZE group were clearer and more transparent, indicating that spraying lysine can reduce the risk of bacterial infection in the early stage of subconjunctival injury.
[0036] Figure 4 The slit lamp photos (A), subconjunctival H&E images (B), and inflammatory cell infiltration statistics (C) of the blank control group (Control), blank core-shell nanofiber membrane group (PZE), and double-loaded core-shell nanofiber membrane treatment group (PRZCE) 7 days after surgery. On the 7th day after surgery, slit lamp examination showed that the conjunctiva of the Control group and the PZE group was severely congested and edematous ( Figure 4 A), H&E staining showed extensive inflammatory cell infiltration ( Figure 4 B), the severity of conjunctival congestion and edema in the PRZCE group was significantly reduced, and H&E showed that inflammatory cell infiltration was significantly reduced, and statistical analysis was significant ( Figure 4 C), indicating that the release of rutin in the early shell can indeed alleviate the inflammatory response.
[0037] Figure 5The slit lamp photos (A), subconjunctival H&E photos (B), Masson staining photos (C), inflammatory cell infiltration statistics photos (D) and Masson staining statistics photos (E) of the blank control group (Control), blank core-shell nanofiber membrane group (PZE) and double-loaded core-shell nanofiber membrane treatment group (PRZCE) 8 weeks after surgery. 8 weeks after surgery, no postoperative infection occurred in any group, no obvious inflammation was found in the anterior chamber of any group, and the lens was transparent; no obvious congestion was found in any group ( Figure 5 A). H&E further showed that there was no obvious inflammatory cell infiltration in each group ( Figure 5 B and 5C). In contrast, Masson staining showed that a large amount of collagen deposition and subconjunctival fibrosis were present in the Control and PZE groups ( Figure 5 C), the collagen synthesis in the PRZCE group was significantly reduced, indicating that tripterygium wilfordii can inhibit the formation of subconjunctival collagen. Compared with the Control group and the PZE group, the difference was statistically significant ( Figure 5 E, P<0.05). The results showed that implantation of double-loaded core-shell nanofiber membrane under the conjunctiva could significantly inhibit subconjunctival inflammation and fibrosis.
[0038] Figure 6 H&E images of eye tissues in the normal group (Normol), blank control group (Control), blank core-shell nanofiber membrane group (PZE), and double-loaded core-shell nanofiber membrane treatment group (PRZCE) were taken 8 weeks after surgery. The results showed that there were no significant differences in the cornea, iris, lens, and retina structure in the PRZCE group compared with the Normal group and the Control group. This shows that the double-loaded core-shell nanofiber membrane is eye-safe.
[0039] In summary, rutin and tripterygium wilfordii are hydrophobic drugs. The present invention first adopts a coaxial electrospinning process to prepare a double-loaded core-shell nanofiber membrane with rutin loaded in the shell layer and tripterygium wilfordii loaded in the core layer. The surface of the membrane is coated with polylysine, which can further improve its apparent solubility and reduce the risk of bacterial infection in the early stage of subconjunctival injury. The administration method of direct implantation under the conjunctiva during surgery allows tripterygium wilfordii to continue to act slowly on the target tissue, thereby improving the bioavailability of rutin and tripterygium wilfordii. Animal experiments have shown that implantation of a double-loaded core-shell nanofiber membrane can significantly reduce the degree of subconjunctival inflammation and fibrosis, and can achieve efficient intervention in subconjunctival inflammation and fibrosis. This innovative research provides new ideas and methods for the treatment of ocular inflammation and fibrosis, and is expected to break through the limitations of traditional treatments and open up new paths for the clinical treatment of related eye diseases.
Claims
1. A dual-loaded core-shell nanofiber membrane, characterized in that: It includes a core-shell nanofiber membrane, which is coated or impregnated with polylysine or chitosan; the core-shell nanofiber membrane is composed of core-shell nanofibers, the shell layer of the core-shell nanofibers is a first degradable biomaterial nanofiber, and the core layer is a second degradable biomaterial nanofiber, the first degradable biomaterial nanofiber is loaded with a drug with anti-inflammatory function, and the second degradable biomaterial nanofiber is loaded with a drug with anti-fibrosis function.
2. The dual-loaded core-shell nanofiber membrane according to claim 1, characterized in that: The first degradable biomaterial and the second degradable biomaterial may be the same or different, and the first degradable biomaterial and the second degradable biomaterial may be independently one of polylactic acid and zein.
3. The dual-loaded core-shell nanofiber membrane according to claim 1, characterized in that: Calculated as a percentage by mass of the first degradable biomaterial nanofibers, the loading amount of the drug with anti-inflammatory function on the first degradable biomaterial nanofibers is 5~9wt%; calculated as a percentage by mass of the second degradable biomaterial nanofibers, the loading amount of the drug with anti-fibrosis function on the second degradable biomaterial nanofibers is 0.125~0.325wt%.
4. The dual-loaded core-shell nanofiber membrane according to claim 1, characterized in that: Drugs with anti-inflammatory function and drugs with anti-fibrosis function are both natural medicines.
5. The dual-loaded core-shell nanofiber membrane according to claim 4, characterized in that: The drug with anti-inflammatory function is rutin, and the drug with fibrosis inhibition function is tripterygium wilfordii.
6. A method for preparing a dual-loaded core-shell nanofiber membrane according to any one of claims 1 to 5, characterized in that: Here are the steps: S1. Preparation of shell layer spinning solution and core layer spinning solution: Shell spinning solution: dissolving the first degradable biomaterial and the drug with anti-inflammatory function in the first solvent, stirring evenly, to obtain the shell spinning solution; Core layer spinning solution: dissolving the second degradable biomaterial and the drug having the function of inhibiting fibrosis in the second solvent, stirring evenly, to obtain the core layer spinning solution; S2, coaxial electrospinning: The shell layer spinning solution and the core layer spinning solution are coaxially electrospun and then dried to obtain a core-shell nanofiber membrane; S3, coating or impregnation: The core-shell nanofiber membrane is immersed in a polylysine aqueous solution or a chitosan aqueous solution or the polylysine aqueous solution or the chitosan aqueous solution is sprayed on the core-shell nanofiber membrane and then dried to prepare a dual-loaded core-shell nanofiber membrane.
7. The method for preparing a dual-loaded core-shell nanofiber membrane according to claim 6, characterized in that: When the first degradable biomaterial or the second degradable biomaterial is polylactic acid, the corresponding first solvent or the second solvent is chloroform; when the first degradable biomaterial or the second degradable biomaterial is zein, the corresponding first solvent or the second solvent is glacial acetic acid; the concentration of the first degradable biomaterial in the shell layer spinning solution is 10~14wt%, and the concentration of the second degradable biomaterial in the core layer spinning solution is 20~25wt%; the concentration of the polylysine aqueous solution or the chitosan aqueous solution is 15~25μg / mL.
8. The method for preparing the dual-loaded core-shell nanofiber membrane according to claim 6, characterized in that: The conditions for coaxial electrospinning are: temperature 25~30℃, relative humidity 45~50%, voltage 18~22kV, using a coaxial needle with a shell needle specification of 18G and a core needle specification of 22G, shell spinning speed 0.0002~0.0005mm / s, core spinning speed 0.0001~0.0003mm / s and shell spinning speed > core spinning speed, receiving distance 12~15cm.
9. Use of the double-loaded core-shell nanofiber membrane as claimed in any one of claims 1 to 5 in the preparation of drugs with anti-inflammatory and anti-fibrosis functions.
10. Use of the double-loaded core-shell nanofiber membrane according to claim 9 in preparing a drug for treating subconjunctival lesions.