Anti-inflammatory poly (lactic-co-glycolic acid) anti-adhesion fiber membrane and preparation method thereof

The preparation of modified polyethylene lactide fiber membrane and spraying of pH-responsive drug-loading polymer vesicles, an anti-inflammatory polyethylene lactide anti-adhesion fiber membrane was formed, which solved the poor flexibility and degradation of polyethylene lactide materials. The postoperative wound inflammation caused by acidity during the process has achieved the effect of reducing the postoperative recovery cycle and improving patient comfort.

CN119455143APending Publication Date: 2025-02-18ENERGY RESOURCES INST HEBEI ACADEMY OF SCI +1
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Patent Information

Application Number
CN202411671368.0
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-11-21
Publication Date
2025-02-18

AI Technical Summary

Technical Problem

The existing polyethylene lactide materials have poor flexibility and long degradation cycle. The acid produced during the degradation process can easily cause postoperative inflammation of wound tissue.

Method used

By preparing modified polyethylene lactide fiber membranes, L-alanine-diol-L-alanine monomer products are prepared using small molecule diol and L-alanine, and cross them with glycolide and alanine. The esters and the like are copolymerized to form a diol-L-alanine-polyethylene lactide modified copolymer, and a modified fiber membrane is prepared by electrospinning. At the same time, electrostatic spraying method was used to spray the pH-responsive drug-loading polymer vesicles onto the fiber membrane to form an anti-inflammatory polyethylene lactide anti-adhesion fiber membrane.

Benefits of technology

The Tg of the modified fiber membrane is within the range of 36-39℃, and the surface wettability is significantly improved. The acid produced during the degradation process promotes the opening of the pH-responsive vesicle membrane pores, and the release of anti-inflammatory drugs to prevent inflammation of wound tissue after surgery. , reduce the postoperative recovery cycle and improve patient comfort.

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Abstract

The invention discloses an anti-inflammatory poly (lactic-co-glycolic acid) anti-adhesion fiber membrane and a preparation method thereof, the preparation method comprises the following steps: A, preparing a micromolecular diol modified poly (lactic-co-glycolic acid) copolymer and poly (lactic-co-glycolic acid) into an electrostatic spinning solution, and preparing a modified poly (lactic-co-glycolic acid) fiber membrane through electrostatic spinning; b, adopting a reversible addition-fragmentation chain transfer dispersion polymerization method to prepare a pH responsive drug-loaded polymer vesicle; and C, spraying the pH-responsive drug-loaded polymer vesicle aqueous solution onto the modified poly (lactic-co-glycolic acid) fiber membrane by adopting an electrostatic spraying method to obtain the anti-inflammatory poly (lactic-co-glycolic acid) anti-adhesion fiber membrane. According to the anti-inflammatory poly (lactic-co-glycolic acid) anti-adhesion fiber membrane prepared by the method, the hydrophilicity of a membrane material is remarkably improved, meanwhile, adhesion and inflammation of tissues at a postoperative wound are prevented, and the comfort of a patient is improved; the pH value of acid generated in the degradation process of the fiber membrane is 5-6.5, membrane holes of the pH-responsive vesicles are just promoted to be opened, the degradation period is shortened, and meanwhile the anti-inflammatory drug is slowly released.
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Description

Technical Field

[0001] The invention relates to an anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane and a preparation method thereof, and belongs to the field of medical polymer materials. Background Art

[0002] Poly(lactic acid) is widely used in the field of biodegradable materials such as postoperative isolation membranes due to its excellent biodegradability, biocompatibility and mechanical properties. However, the glass transition temperature (Tg) of conventional poly(lactic acid) materials is 50-55°C, the flexibility is poor, the acidic pH range produced after degradation is wide, the degradation cycle is long, the patient is uncomfortable after implantation in the human body, and the acid produced during the degradation process is prone to cause inflammation of postoperative wound tissue. Although the poly(lactic acid) drug-loaded fiber membrane prepared by CN114470322A alleviates the problem of slow degradation rate of poly(lactic acid) to a certain extent, and improves the sustained release performance of poly(lactic acid) fiber membrane drug loading, its drug loading is mainly used for early treatment, and the problem of tissue inflammation caused by late poly(lactic acid) degradation has not been solved, and the patient will still feel uncomfortable after implantation in the body after surgery. Summary of the invention

[0003] The present invention aims to provide an anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane and a preparation method thereof, so as to solve the problems that the existing poly(lactide-glycol) material has poor flexibility, a long degradation period, and the acid generated during the degradation process easily causes inflammation of postoperative wound tissue.

[0004] The object of the present invention is achieved in that:

[0005] A method for preparing an anti-inflammatory poly(lactide-glycol)-anti-adhesion fiber membrane comprises the following steps:

[0006] A. Preparation of modified poly(lactide-glycolide) fiber membrane:

[0007] A L-alanine-diol-L-alanine monomer product is prepared using a small molecule diol and L-alanine as raw materials, specifically, the small molecule diol, L-alanine, p-toluenesulfonic acid monohydrate, and toluene are refluxed at 120-150° C., purified after precipitation, and washed and dried with a sodium carbonate aqueous solution to obtain an L-alanine-diol-L-alanine monomer product;

[0008] The diol-L-alanine-poly(glycol-lactide) modified copolymer is prepared using L-alanine-diol-L-alanine monomer product, glycolide and lactide as raw materials, specifically, L-alanine-diol-L-alanine monomer product, glycolide, lactide, stannous octoate and toluene are reacted at 110-140° C. for 12-18 hours to obtain the diol-L-alanine-poly(glycol-lactide) modified copolymer;

[0009] The modified copolymer of glycol-L-alanine-poly(lactide-glycol) and poly(lactide-glycol) are added into a mixed solvent to prepare an electrospinning solution, and the modified poly(lactide-glycol) fiber membrane is prepared by electrospinning.

[0010] The pH of the acid produced during the degradation of the obtained modified poly(lactide-glycol) fiber membrane is 5-6.5.

[0011] B. Preparation of pH-responsive drug-loaded polymer vesicles:

[0012] 2-(diisopropylamino)ethyl methacrylate, 2-methacryloyloxyethyl phosphorylcholine, N-isopropylacrylamide, glycidyl methacrylate, a self-made macromolecular chain transfer agent, an initiator and a solvent are added to a reactor, sealed after deoxygenation, and reacted at 30-80°C for 5-8h to obtain a polymer vesicle emulsion; after diluting the polymer vesicle emulsion, a diamine is added, and the reaction is stirred to obtain a cross-linked polymer vesicle; the cross-linked polymer vesicle is dispersed in an acidic buffer solution, an anti-inflammatory drug is added, and the drug is loaded, stirred for 12-24h, and then the solution is adjusted to alkaline, and the unloaded drug is removed by dialysis to obtain a pH-responsive drug-loaded polymer vesicle;

[0013] The preparation method of the self-made macromolecular chain transfer agent is detailed in Example 1 of CN117045603A. N-isopropylacrylamide monomer units are introduced during the preparation of polymer vesicles to better combine with the modified poly(lactide-glycolide) fiber membrane.

[0014] C. Preparation of anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane:

[0015] The pH-responsive drug-loaded polymer vesicle aqueous solution is sprayed onto the modified poly(lactide-glycol) fiber membrane obtained in step A by electrostatic spraying. The anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane is obtained after drying through the hydrogen bond interaction between the alcohol hydroxyl group and amide group on the modified fiber membrane and the amide group and phosphorylcholine group in the polymer vesicle structure.

[0016] Furthermore, the small molecule diol in step A is any one of ethylene glycol, propylene glycol and butanediol.

[0017] Furthermore, the molar ratio of the small molecule diol to L-alanine in step A is 1:(2-2.2).

[0018] Furthermore, in step A, the molar ratio of the L-alanine-diol-L-alanine monomer product, glycolide, and lactide is 1:(1-1.5):(2.5-3.5).

[0019] Furthermore, in step A, the molar ratio of the monomers lactide to glycolide in the poly(lactide-glycolide) is (2.5-3.5):1.

[0020] Furthermore, in the electrospinning solution of step A, the glycol-L-alanine-poly(lactide-glycol) modified copolymer accounts for 0-20% of the sum of the mass of the glycol-L-alanine-poly(lactide-glycol) and poly(lactide-glycol) by weight, preferably 10% to 20%, and more preferably 15%.

[0021] Furthermore, the spinning solution concentration in step A is 0.35-0.55 g / mL; the electrospinning conditions are: spinning voltage is 12-28 kV, injection speed is 0.4-1.8 mL / h, and receiving distance is 10-18 cm.

[0022] Furthermore, in step B, the molar ratio of the monomers 2-(diisopropylamino)ethyl methacrylate, 2-methacryloyloxyethyl phosphorylcholine, N-isopropylacrylamide, and glycidyl methacrylate is (1-19):(0.01-5):(0.1-1):1; and the solid content of the polymer vesicle emulsion is 5-30%.

[0023] Furthermore, in step B, the concentration of the anti-inflammatory drug is 5-20 mg / mL; the anti-inflammatory drug is any one of penicillin, doxorubicin hydrochloride, and streptomycin.

[0024] Furthermore, the concentration of the pH-responsive drug-loaded polymer vesicle aqueous solution in step C is 0.5-5 mg / mL; the electrostatic spraying conditions are: voltage 12-28 kV, injection speed 0.6-1.5 mL / h, and receiving distance 12-18 cm.

[0025] The present invention also provides an anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane prepared according to the method.

[0026] Beneficial effects of the present invention:

[0027] The present invention obtains an anti-inflammatory poly(lactic acid)-lactide anti-adhesion fiber membrane by hydrogen bonding interaction between the polyhydroxyl groups and amide groups on the modified copolymer and the amide groups and phosphorylcholine groups in the molecular structure of the polymer vesicle. First, the poly(lactic acid)-lactide fiber membrane modified with small molecule diol is prepared by electrospinning technology. g It can be in the range of 36-39℃, which matches the human body temperature, and the surface wettability is significantly improved, further preventing adhesion of tissue at the wound; then the pH-responsive vesicle aqueous solution is sprayed onto the modified fiber membrane by electrostatic spraying. The acid produced during the degradation of the modified fiber membrane prompts the pH-responsive vesicle membrane pores to open, slowly releasing anti-inflammatory drugs such as penicillin antibiotics, preventing inflammation of tissue near the wound, reducing the postoperative recovery period, and improving patient comfort. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is the particle size spectrum of responsive drug-loaded polymer vesicles at different pH.

[0029] Figure 2 This is a graph of the particle size of responsive drug-loaded polymer vesicles under alternating pH cycles.

[0030] Figure 3 TEM images of responsive drug-loaded polymer vesicles at different pH values.

[0031] Figure 4 This is the degradation test spectrum of modified poly(lactide-glycol) fiber membrane. Figure 5 It is the in vitro drug release spectrum of the anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane. DETAILED DESCRIPTION

[0032] The specific implementation method is further described in detail below in conjunction with the embodiments.

[0033] The preparation method of the anti-inflammatory poly(lactic acid)-glycolide anti-adhesion fiber membrane of the present invention comprises the following steps: poly(lactic acid)-glycolide is compounded with a modified polymer, an anti-adhesion fiber membrane is obtained by electrostatic spinning, and then a pH-responsive drug-loaded polymer vesicle aqueous solution with a concentration of 0.5-5 mg / mL is sprayed onto the modified fiber membrane by an electrostatic spray method, that is, the anti-inflammatory poly(lactic acid)-glycolide anti-adhesion fiber membrane is obtained by hydrogen bond interaction between the alcohol hydroxyl group and the amide group in the molecular structure of the modified fiber membrane and the amide group and the phosphorylcholine group in the molecular structure of the polymer vesicle. The Tg of the modified fiber membrane can be within the range of 36-39°C, and the surface wettability is significantly improved; the acid generated during the degradation of the modified fiber membrane prompts the pH-responsive vesicle membrane pores to open, and slowly releases anti-inflammatory drugs such as penicillin antibiotics, thereby preventing postoperative wound tissue adhesion and inhibiting inflammation of wound healing tissue, thereby improving patient comfort.

[0034] Example 1

[0035] The method for preparing the anti-inflammatory poly(lactide-glycol)-anti-adhesion fiber membrane of this embodiment comprises the following steps:

[0036] A. Preparation of modified poly(lactide-glycolide) fiber membrane:

[0037] 0.01 mol ethylene glycol, 0.02 mol L-alanine, 0.02 mol p-toluenesulfonic acid monohydrate (TsOH·H2O) and 100 mL toluene were refluxed at 130°C for 20 h, precipitated, purified by petroleum ether-isopropanol-petroleum ether, washed and dried by adding 1 mol / L sodium carbonate aqueous solution, and amino group was deprotected to obtain L-alanine-diol-L-alanine monomer product;

[0038] 0.01 mol of the above monomer product, 0.01 mol of glycolide, 0.03 mol of lactide, 5 mL of stannous octoate and 50 mL of purified toluene were reacted at 120° C. for 12 h, precipitated, purified by petroleum ether-isopropanol-petroleum ether, and dried for 12 h to obtain a glycol-L-alanine-poly(glycolide)-lactide modified copolymer;

[0039] Weigh 1.913g of poly(lactide-glycol) and 0.337g of diol-L-alanine-poly(lactide-glycol) modified copolymer and place them in a sealed bottle (the mass of diol-L-alanine-poly(lactide-glycol) modified copolymer accounts for 15% of the total mass of the polymer), and then add 5mL of a mixed solvent of acetone and N,N-dimethylformamide, the volume ratio of acetone and N,N-dimethylformamide in the mixed solvent is 1:1, stir thoroughly, and obtain 0.45g / mL of spinning solution; the conditions of electrospinning are: spinning voltage of 20kV, injection distance of 16cm, injection speed of 1.2mL / h, injection time of 220min, and obtain a modified poly(lactide-glycol) fiber membrane.

[0040] B. Preparation of pH-responsive drug-loaded polymer vesicles: A reversible addition-fragmentation chain transfer dispersion polymerization method was used. Specifically, 1.034 g of 2-(diisopropylamino)ethyl methacrylate, 0.2045 g of 2-methacryloyloxyethyl phosphorylcholine, 0.0785 g of N-isopropylacrylamide, 0.1970 g of glycidyl methacrylate, 0.1162 g of a homemade macromolecular chain transfer agent, 0.04 g of potassium persulfate, 6.1851 g of ethanol and 2.6458 g of water were added to a reaction bottle, sealed after deoxygenation, and reacted at 30°C. The polymer vesicle emulsion is obtained after 7 hours; the polymer vesicle emulsion is diluted 20 times, ethylenediamine is added to react with the epoxy groups on the polymer vesicles, and cross-linked polymer vesicles are obtained after stirring at room temperature for 24 hours; 1.0-5.0g of the above cross-linked polymer vesicle emulsion is weighed, dispersed in a phosphate buffered saline solution with a pH of 5.0-6.0 after centrifugation, 5-20mg / mL of penicillin antibiotics and anti-inflammatory drugs are added, and the solution is stirred at room temperature for 12-24 hours for drug encapsulation, and the pH value of the phosphate buffered saline solution is adjusted to 8.0, and dialyzed for 3-5 days to obtain pH-responsive drug-loaded polymer vesicles.

[0041] C. Preparation of anti-inflammatory poly(lactic acid)-binding lactide anti-adhesion fiber membrane: 1 mg / mL pH-responsive drug-loaded polymer vesicle aqueous solution was sprayed onto the modified poly(lactic acid)-binding lactide fiber membrane by electrostatic spraying, wherein the volume ratio of the drug-loaded polymer vesicle aqueous solution to the modified fiber membrane spinning solution in step A was 1:2. At 25°C, the spray voltage was 20 kV, the injection distance was 16 cm, and the injection speed was 1.2 mL / h. After collection, the membrane was dried at room temperature for 24 h to obtain the anti-inflammatory poly(lactic acid)-binding lactide anti-adhesion fiber membrane.

[0042] The T of the obtained anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane g The temperature of the membrane surface is 37.6℃, which is consistent with the human body temperature. The surface wetting time of the membrane is only 55s. The introduction of polyhydroxy groups significantly enhances the surface wettability of the modified polymer membrane, which enhances the comfort of patients. In addition, the average fiber diameter is 2200-2300nm, the elongation at break is 190-210%, and the degradation cycle is 2-3 months. While reducing the degradation cycle of poly(lactide-glycolide) materials, it regulates the sustained release of penicillin antibiotics and anti-inflammatory drugs in polymer vesicles to prevent inflammation of tissues at the wound healing site after surgery.

[0043] pH responsiveness test of drug-loaded polymer vesicles:

[0044] The size change of drug-loaded polymer vesicles was monitored by adjusting the pH value of the solution (see Figure 1 ), when the solution pH is higher than 6.5, the particle size of the cross-linked vesicles is about 800nm ​​because the tertiary amine groups on the polymer vesicle segments are not protonated. When the solution pH is less than 6.0, the tertiary amine groups on the segments are protonated, the cross-linked vesicle walls are swollen, and the particle size increases to about 1600nm, and Figure 1 To further illustrate the pH responsiveness of the drug-loaded polymer vesicles, the polymer vesicles were alternately cycled for 5 times in pH = 5.0 and pH = 8.0 phosphate buffer solutions (adjusted by adding 0.1 mmol sodium hydroxide aqueous solution and 0.1 mmol hydrochloric acid aqueous solution), and the particle size of the polymer vesicles was observed (see Figure 2 ), which showed good reversibility, stability and pH responsiveness. In addition, the morphology of drug-loaded polymer vesicles in pH = 5.0 and pH = 8.0 solvents was observed by transmission electron microscopy (see Figure 3 ), showing a larger vesicle structure at pH = 5.0.

[0045] Degradability test of modified poly(lactide-glycol) fiber membrane:

[0046] At 180°C and 10MPa, a 1.0mm thick polymer sheet was obtained by hot pressing on a flat vulcanizer and cut into 20mm×20mm×1.0mm samples. The sample was placed in 10mL of phosphate buffer (pH=7.4) and the material degradation experiment was carried out in a 37°C constant temperature incubator shaker. After the preset sampling time, the pH value of the solution was recorded until the sample was completely degraded. The acid pH produced after complete degradation was 5-6.5 (see Figure 4 ).

[0047] In vitro drug release test of anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane:

[0048] Weigh 12 mg of the above anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane and 12 mL of phosphate buffered saline solution with a pH of 7.4 into a 25 mL centrifuge tube to prepare 3 parallel samples; then place the sample on a 37°C shaker to mix evenly, take 2 mL of samples at intervals of 1 h, 2 h, 4 h, 8 h, 16 h, 24 h, 36 h, 48 h, 60 h, 72 h, 96 h and 120 h, respectively, and replenish the pH of 7.4 phosphate buffered saline solution (2 mL) to 25 mL in time; test the concentration of the sample by ultraviolet spectrophotometer, and further calculate the cumulative release of the drug to be 25.1 μg (see Figure 5 ).

[0049] Example 2

[0050] This embodiment is based on the embodiment 1 with the following changes.

[0051] Weigh 1.594 g of poly(lactide-glycol) and 0.281 g of a glycol-L-alanine-poly(lactide-glycol) modified copolymer and place them in a sealed bottle (the mass of the glycol-L-alanine-poly(lactide-glycol) modified copolymer accounts for 15% of the total mass of the polymer), and then add 5 mL of a mixed solvent of acetone and N,N-dimethylformamide, wherein the volume ratio of the mixed solvent acetone and N,N-dimethylformamide is 1:1, stir well, and obtain a spinning solution of 0.375 g / mL; the electrospinning conditions are the same as those in Example 1 to obtain a modified poly(lactide-glycol) fiber membrane.

[0052] A 0.5 mg / mL pH-responsive vesicle aqueous solution was sprayed onto the modified poly(lactide-glycol) fiber membrane by electrostatic spraying, and the spraying conditions were the same as those in Example 1 to obtain an anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane.

[0053] T of anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane g The temperature is 37.6℃, which is consistent with human body temperature; the average fiber diameter is 1200-1500nm, the elongation at break is 135-155%, and the degradation cycle is 1-2 months.

[0054] Example 3

[0055] This embodiment is based on the embodiment 1 with the following changes.

[0056] Weigh 2.025 g of poly(lactide-glycol) and 0.225 g of a glycol-L-alanine-poly(lactide-glycol) modified copolymer and place them in a sealed bottle (the mass of the glycol-L-alanine-poly(lactide-glycol) modified copolymer accounts for 10% of the total mass of the polymer), and then add 5 mL of a mixed solvent of acetone and N,N-dimethylformamide, wherein the volume ratio of the mixed solvent of acetone and N,N-dimethylformamide is 1:1, stir well, and obtain a spinning solution of 0.45 g / mL; the electrospinning conditions are the same as those in Example 1 to obtain a modified poly(lactide-glycol) fiber membrane.

[0057] A 5 mg / mL pH-responsive vesicle aqueous solution was sprayed onto the modified poly(lactide-glycol) fiber membrane by electrostatic spraying at 25°C under the same spraying conditions as in Example 1. After collection, the membrane was dried at room temperature for 24 hours to obtain an anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane.

[0058] The obtained anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane has a wetting time of 170-190s, T g The temperature is 40.4°C, the average fiber diameter is 2200-2350nm, the elongation at break is 180-200%, and the degradation period is 3-4 months.

[0059] Example 4

[0060] Weigh 0.45 g of diol-L-alanine-poly(lactide-glycol) modified copolymer and 1.8 g of poly(lactide-glycol) into a sealed bottle (the mass of the modified copolymer accounts for 20% of the total mass of the polymer), and then add 5 mL of a mixed solvent of acetone and N,N-dimethylformamide, wherein the volume ratio of the mixed solvent acetone and N,N-dimethylformamide is 1:1, stir well, and obtain a spinning solution of 0.45 g / mL; the electrospinning conditions are the same as those in Example 1 to obtain a poly(lactide-glycol) anti-adhesion fiber film.

[0061] A 5 mg / mL pH-responsive vesicle aqueous solution was sprayed onto the modified poly(lactide-glycol) fiber membrane by electrostatic spraying at 25°C under the same spraying conditions as in Example 1. After collection, the membrane was dried at room temperature for 24 hours to obtain an anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane.

[0062] The T of the obtained anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane g The temperature is 31.3°C, the wetting time is 10s, the average fiber diameter is 2200-2400nm, the elongation at break is 180-200%, and the degradation period is 1-2 months.

[0063] Example 5

[0064] Weigh 2.25 g of poly(lactide-glycol) (without adding glycol-L-alanine-poly(lactide-glycol) modified copolymer) and place it in a sealed bottle, add 5 mL of mixed solvent acetone and N,N-dimethylformamide, the volume ratio of the mixed solvent acetone and N,N-dimethylformamide is 1:1, stir well to obtain 0.45 g / mL spinning solution; the conditions of electrospinning are the same as those in Example 1 to obtain a modified poly(lactide-glycol) fiber membrane.

[0065] 5 mg / mL pH-responsive vesicle aqueous solution was sprayed onto the modified poly(lactic acid) glycolide fiber membrane by electrostatic spraying at 25°C under the same spraying conditions as in Example 1. After collection, it was dried at room temperature for 24 hours to obtain an anti-inflammatory poly(lactic acid) glycolide anti-adhesion fiber membrane.g It is 52.2℃, which is quite different from human body temperature. The membrane surface wetting time is greater than 300s. The average fiber diameter is 2200-2400nm, the elongation at break is 140-160%, and the degradation period is greater than 6 months.

[0066] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing an anti-inflammatory poly(lactide-glycol)-anti-adhesion fiber membrane, characterized in that: The steps include: A. Preparation of modified poly(lactide-glycolide) fiber membrane: The monomer product of L-alanine-diol-L-alanine is prepared by using small molecule diol and L-alanine as raw materials; the monomer product of L-alanine-diol-L-alanine, glycolide and lactide are prepared by using diol-L-alanine-polyglycolide-lactide modified copolymer as raw materials; Adding glycol-L-alanine-poly(lactide-glycol) modified copolymer and poly(lactide-glycol) into a mixed solvent to prepare an electrospinning solution, and preparing a modified poly(lactide-glycol) fiber membrane by electrospinning; B. Preparation of pH-responsive drug-loaded polymer vesicles: 2-(diisopropylamino)ethyl methacrylate, 2-methacryloyloxyethyl phosphorylcholine, N-isopropylacrylamide, glycidyl methacrylate, macromolecular chain transfer agent, initiator and solvent are added to a reactor, sealed after deoxygenation, and reacted to obtain a polymer vesicle emulsion; after diluting the polymer vesicle emulsion, a diamine is added, and the reaction is stirred to obtain a cross-linked polymer vesicle; the cross-linked polymer vesicle is dispersed in an acidic buffer solution, an anti-inflammatory drug is added, and the drug is loaded, stirred for 12-24 hours, and then the solution is adjusted to alkaline, and the unloaded drug is dialyzed to obtain a pH-responsive drug-loaded polymer vesicle; C. Preparation of anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane: The pH-responsive drug-loaded polymer vesicle aqueous solution is sprayed onto the modified poly(lactide-glycol) fiber membrane obtained in step A by an electrostatic spray method, and the anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane is obtained after drying.

2. The method for preparing the anti-inflammatory poly(lactide-glycol)-anti-adhesion fiber membrane according to claim 1, characterized in that: The small molecule diol in step A is any one of ethylene glycol, propylene glycol and butylene glycol.

3. The method for preparing the anti-inflammatory poly(lactide-glycol)-anti-adhesion fiber membrane according to claim 1, characterized in that: The molar ratio of lactide to glycolide in the poly(lactide-glycolide) in step A is (2.5-3.5):

1.

4. The method for preparing the anti-inflammatory poly(lactide-glycol)-anti-adhesion fiber membrane according to claim 1, characterized in that: In the electrospinning solution of step A, the glycol-L-alanine-poly(lactide-glycol) modified copolymer accounts for 0-20% of the sum of the mass of the glycol-L-alanine-poly(lactide-glycol) modified copolymer and poly(lactide-glycol) modified copolymer.

5. The method for preparing the anti-inflammatory poly(lactide-glycol)-anti-adhesion fiber membrane according to claim 1, characterized in that: In the electrospinning solution of step A, the glycol-L-alanine-poly(lactide-glycol) modified copolymer accounts for 10%-20% of the sum of the mass of the glycol-L-alanine-poly(lactide-glycol) modified copolymer and the poly(lactide-glycol) modified copolymer.

6. The method for preparing the anti-inflammatory poly(lactide-glycol)-anti-adhesion fiber membrane according to claim 1, characterized in that: The spinning solution concentration in step A is 0.35-0.55 g / mL; the electrospinning conditions are: spinning voltage is 12-28 kV, injection speed is 0.4-1.8 mL / h, and receiving distance is 10-18 cm.

7. The method for preparing the anti-inflammatory poly(lactide-glycol)-anti-adhesion fiber membrane according to claim 1, characterized in that: In step B, the molar ratio of the monomers 2-(diisopropylamino)ethyl methacrylate, 2-methacryloyloxyethyl phosphorylcholine, N-isopropylacrylamide, and glycidyl methacrylate is (1-19):(0.01-5):(0.1-1):1; and the solid content of the polymer vesicle emulsion is 5-30%.

8. The method for preparing the anti-inflammatory poly(lactide-glycol)-anti-adhesion fiber membrane according to claim 1, characterized in that: In step B, the concentration of the anti-inflammatory drug is 5-20 mg / mL; the anti-inflammatory drug is any one of penicillin, doxorubicin hydrochloride, and streptomycin.

9. The method for preparing the anti-inflammatory poly(lactide-glycol)-anti-adhesion fiber membrane according to claim 1, characterized in that: The concentration of the pH-responsive drug-loaded polymer vesicle aqueous solution in step C is 0.5-5 mg / mL; the electrostatic spraying conditions are: voltage 12-28 kV, injection speed 0.6-1.5 mL / h, and receiving distance 12-18 cm.

10. The anti-inflammatory poly(lactide-glycol) anti-adhesion fiber membrane prepared according to the method described in any one of claims 1 to 9.

Citation Information

Patent Citations

  • PLGA nano drug-loaded fiber membrane and preparation method thereof

    CN114470322A

  • Preparation method of pH-responsive drug-loaded polymer vesicles

    CN117045603A