Polymer composite membrane for medicine and preparation method of polymer composite membrane

Abstract

The invention relates to the field of medicine composite membranes, in particular to a polymer composite membrane for medicines and a preparation method thereof, which are used for solving the problems of insufficient barrier property and solvent migration pollution risk of the composite membrane. A modified inner-layer film, a modified middle-layer film and an outer-layer film are respectively subjected to corona treatment, then the middle-layer film and the inner-layer film are compounded to obtain a double-layer film, and then the outer-layer film is compounded onto the double-layer film to obtain the polymer composite film. The modified inner-layer film in the preparation method has good moisture-proof barrier property, enhanced mechanical property, good transparency and anti-adhesion property, and the modified middle-layer film remarkably improves the water resistance of the material, improves the mechanical toughness, optimizes the interlayer cohesive force and enhances the chemical resistance, so that the obtained polymer composite film meets the drug contact safety standard, and has good application prospects. The packaging film has high oxygen and water vapor barrier properties so as to prolong the shelf life of drugs, is high in mechanical property and good in adaptability, and can meet the packaging requirements of the drugs such as capsules and tablets.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of pharmaceutical composite film, in particular to a high molecular composite film for pharmaceuticals and a preparation method thereof. BACKGROUND

[0002] As a key protective carrier for drug storage and transportation, the pharmaceutical packaging film plays a vital role in the whole life cycle of the drug. It not only needs to meet the core requirements of blocking oxygen, moisture and light to prevent the drug from deteriorating due to oxidation, deliquescence or photolysis, but also needs to have the performance of no harmful substance migration and good mechanical strength. Among them, no harmful substance migration is to avoid the migration of ingredients in the packaging material to the drug, thereby affecting the quality and safety of the drug; good mechanical strength can protect the packaging film from external forces such as extrusion and collision during drug storage and transportation, and prevent the packaging from being damaged to expose the drug to the external environment.

[0003] However, the existing high molecular film for pharmaceuticals is mostly single-layer structure or simple double-layer composite film, which has the defects of insufficient barrier property and solvent migration pollution risk.

[0004] Therefore, it is an urgent need in the current pharmaceutical packaging field to develop a high molecular composite film for pharmaceuticals with good barrier property, high safety and good mechanical property. SUMMARY

[0005] In order to overcome the above technical problems, the purpose of the present application is to provide a high molecular composite film for pharmaceuticals and a preparation method thereof.

[0006] The purpose of the present application can be achieved by the following technical solutions: In a first aspect, the present application provides a preparation method of a high molecular composite film for pharmaceuticals, comprising the following steps: Step one: mica powder and coupling agent solution are added to a three-necked flask equipped with a stirrer, a thermometer and a gas inlet tube, nitrogen is introduced for protection, and stirring is carried out at a temperature of 25-30 DEG C and a stirring rate of 250-300 r / min for 2-3 h, then it is placed in a vacuum drying box and dried at a temperature of 55-60 DEG C for 4-5 h, then it is crushed by a planetary ball mill at a speed of 470-500 r / min for 10-12 min, and sieved through a 200 mesh screen to obtain modified mica powder; Step two: the coupling agent KH-570 is dissolved in anhydrous ethanol and ultrasonically dispersed for 5-7 min at a power of 280-300 W, then the nano-silica is added, and the mixture is placed in an ultrasonic cleaner and ultrasonically treated for 1-2 h at a temperature of 37-40℃ and a power of 480-500 W, then placed in a vacuum drying oven and dried for 6-7 h at a temperature of 75-80℃, then dispersed with a high-speed dispersing machine at a speed of 9000-10000 r / min for 5-7 min to obtain modified nano-silica; Step three: the low-density polyethylene, modified mica powder, and modified nano-silica are separately vacuum dried for 2-3 h at a temperature of 75-80℃, then blended and granulated using a twin-screw extruder, and then blown into a film on a film blowing machine to obtain a modified inner layer film; Step four: the ethylene-vinyl alcohol copolymer is placed in a vacuum drying oven and dried for 9-10 h at a temperature of 75-80℃, then transferred to a four-necked flask equipped with a stirrer, a thermometer, a spherical condenser, and a dropping funnel, anhydrous ethanol is added, and the mixture is stirred for 2-3 h at a temperature of 55-60℃ and a stirring rate of 150-200 r / min, antioxidant 1010 and a catalyst are added and stirred for 5-7 min, then the four-necked flask is placed in a constant-temperature water bath and heated to 70℃, and acetic anhydride is added dropwise while stirring at a stirring rate of 200-250 r / min, with a dropwise rate of 1-2 drops / s, after the addition is completed, the temperature is maintained at 68-70℃ for 3 h of reaction, after the reaction is completed, the temperature of the flask is reduced to 40℃, and sodium hydroxide solution is added dropwise at a rate of 1-2 drops / s until the pH is 7, and the stirring is continued for 30-35 min, then transferred to a separatory funnel, washed with purified water, and after oscillation for 10-12 min, the layers are separated, the lower layer of salt water is removed, and the water washing operation is repeated for 3-5 times, then transferred to a rotary evaporator and evaporated for 3-4 h at a temperature of 45-50℃ and a rotation speed of 75-80 r / min, then placed in a vacuum drying oven and dried for 7-9 h at a temperature of 55-60℃, then pulverized with a high-speed pulverizer and sieved through an 80-mesh sieve, then cast into a film using a single-screw casting machine to obtain a modified middle layer film; Step five: the polypropylene is placed in a vacuum drying oven and dried at a temperature of 75-80℃ for 4-5h, then added to a single screw extruder, extruded, and then pressed into a thick sheet by a cooling roller, the thick sheet is sent to a longitudinal stretching machine, the preheating temperature is 120-130℃, the stretching temperature is 135-145℃, the stretching ratio is 3.5-4.5 times, and then cooled to 40℃, the longitudinally stretched film is sent to a transverse stretching machine, the preheating temperature is 140-150℃, the stretching temperature is 155-165℃, the stretching ratio is 7-8 times, the heat setting temperature is 160-170℃, then cooled to 40℃, then sent to a corona treatment machine, the treatment power is 30-40W, the treatment speed is 8-10m / min, the surface tension of the film is ≥40mN / m, and an outer layer film is obtained; Step six: the two-component polyurethane adhesive and the mixed solvent are placed in a sealed container and stirred at a stirring rate of 450-500r / min for 15-17min, and then left to stand for 30-32min to remove bubbles, to obtain an adhesive; Step seven: one side of the modified inner layer film is subjected to corona treatment, the treatment power is 30-35W, the treatment speed is 5-6m / min, and the surface tension is ≥38mN / m, to obtain a pretreated inner layer film; Step eight: both sides of the modified middle layer film are subjected to corona treatment, the first side: the power is 25-30W, the speed is 5-6m / min, and the surface tension is ≥36mN / m, the second side: the power is 30-35W, the speed is 5-6m / min, and the surface tension is ≥38mN / m, to obtain a pretreated middle layer film; Step nine: the pretreated middle layer film is installed on the unwinding station of the laminating machine with the first side facing up, the glue roller is set to have a coating amount of 3.0-3.5g / m 2 , to ensure that the adhesive is coated on the first side of the pretreated middle layer film, the laminating parameters are adjusted, the laminating temperature is 65-70℃, the laminating pressure is 0.35-0.4MPa, and the laminating speed is 5-6m / min, the pretreated inner layer film with the corona treated side facing down is laminated with the pretreated middle layer film coated with the adhesive by the laminating roller, and a double-layer laminated film is obtained by winding; Step ten: the double-layer film is unwound, the second side of the pretreated middle layer film faces up, and the adhesive is coated again, the coating amount is 2.5-3.0g / m 2 , the laminating parameters are adjusted, the laminating temperature is 60-65℃, the laminating pressure is 0.3-0.35MPa, and the laminating speed is 4-5m / min, the outer layer film with the corona treated side facing down is laminated with the double-layer film coated with the adhesive, and a three-layer laminated film is obtained by winding, which is placed in a curing room at a temperature of 40-45℃ for 48h to obtain a high molecular laminated film.

[0007] As a preferred embodiment of the present application, the amount ratio of the mica powder and the coupling agent solution in step one is 100-110g:200-220mL.

[0008] As a preferred embodiment of the present application, the coupling agent solution in step one is a solution of coupling agent KH-550 and anhydrous ethanol mixed in a volume ratio of 1:10.

[0009] As a preferred embodiment of the present application, the particle size of the mica powder in step one is 500-1000 mesh.

[0010] As a preferred embodiment of the present application, the amount ratio of the coupling agent KH-570, anhydrous ethanol and nano-silica in step two is 15-17mL:300-330mL:50-55g.

[0011] As a preferred embodiment of the present application, the particle size of the nano-silica in step two is 10-20nm.

[0012] As a preferred embodiment of the present application, the amount ratio of the low-density polyethylene, modified mica powder and modified nano-silica in step three is 92-184g:5-10g:2-4g.

[0013] As a preferred embodiment of the present application, the low-density polyethylene in step three is LD26D of Lanzhou Petrochemical.

[0014] As a preferred embodiment of the present application, the amount ratio of the ethylene-vinyl alcohol copolymer, anhydrous ethanol, antioxidant 1010, catalyst and acetic anhydride in step four is 10-12g:80-95mL:0.01-0.02g:10-12mL:1.2-1.4mL.

[0015] As a preferred embodiment of the present application, the catalyst in step four is a solution of p-toluenesulfonic acid and anhydrous ethanol mixed in an amount ratio of 0.05g:10mL.

[0016] As a preferred embodiment of the present application, the mass fraction of the sodium hydroxide solution in step four is 4%.

[0017] As a preferred embodiment of the present application, the ethylene-vinyl alcohol copolymer in step four is EVAL F101B of Japan Kuraray.

[0018] As a preferred embodiment of the present application, the polypropylene in step five is medical grade, Yanshan Petrochemical, model K4912.

[0019] As a preferred embodiment of the present application, the ratio of the two-component polyurethane adhesive to the mixed solvent in step six is 10-20 mL: 20-40 mL.

[0020] As a preferred embodiment of the present application, the mixed solvent in step six is a solvent formed by mixing ethyl acetate and butanone in a volume ratio of 3:1.

[0021] As a preferred embodiment of the present application, the two-component polyurethane adhesive in step six is HANGO LOCTITE LIOFOL LA 7835 / LA 6256.

[0022] In a second aspect, the present application provides a polymer composite film for pharmaceuticals, which is prepared according to the preparation method of the polymer composite film of the first aspect.

[0023] The present application has the following advantages: The present application provides a polymer composite film for pharmaceuticals and a preparation method thereof. The modified inner layer film, the modified middle layer film, and the outer layer film are subjected to corona treatment, respectively. Then, the middle layer film and the inner layer film are combined to obtain a double-layer film. Finally, the outer layer film is combined to the double-layer film to obtain the polymer composite film. The modified inner layer film has good moisture-proof barrier, mechanical property enhancement, good transparency, and anti-blocking performance. The modified middle layer film significantly improves the water resistance, mechanical toughness, interlayer adhesion, and chemical resistance of the material. The obtained polymer composite film meets the safety standards for pharmaceutical contact, has high oxygen and water vapor barrier properties to prolong the shelf life of the pharmaceuticals, and has strong mechanical properties and good adaptability, which can meet the packaging requirements of capsules, tablets, and other pharmaceuticals.

[0024] In the preparation process of the polymer composite film for pharmaceuticals, a modified inner layer film is first prepared. Mica powder and a coupling agent solution are stirred and reacted to fully react the amino groups of the coupling agent with the hydroxyl groups on the surface of the mica (to form Si-O-Al bonds), thereby obtaining modified mica powder. The coupling agent KH-570, anhydrous ethanol, and nano-silicon dioxide are subjected to ultrasonic treatment to react the double bonds of the coupling agent KH-570 with the hydroxyl groups on the surface of the silicon dioxide. The modified nano-silicon dioxide is obtained after drying and dispersing. Low-density polyethylene, modified mica powder, and modified nano-silicon dioxide are blended and granulated using a twin-screw extruder, and then blown into a film to obtain the modified inner layer film. Mica is a layered silicate that forms a sheet-shaped barrier network when dispersed in low-density polyethylene, thereby prolonging the water vapor permeation path. Nano-silicon dioxide can fill the small gaps between the mica layers, further blocking water vapor. The combination of the two improves the moisture-proof and barrier properties of low-density polyethylene. Mica enhances the rigidity of the material, and nano-silicon dioxide improves the toughness of the material. Both fillers are chemically inert and do not release harmful substances to pollute the pharmaceuticals, thereby meeting the pharmaceutical contact regulations. The modified inner layer film has good moisture-proof barrier, mechanical property enhancement, good transparency, and anti-blocking performance.

[0025] In the process of preparing a high molecular composite film for pharmaceutical products, a modified middle layer film is prepared. First, ethylene-vinyl alcohol copolymer and anhydrous ethanol are stirred and reacted, then antioxidant 1010 and a catalyst are added, and acetic anhydride is added dropwise for reaction. Acetic anhydride acts as an esterifying agent and, under the action of the catalyst, acylates the hydroxyl groups on the molecular chain of the ethylene-vinyl alcohol copolymer to form acetic ester groups. The product is then filtered, washed, dried, and crushed, and then cast into a film to obtain the modified middle layer. The oxygen barrier property of ethylene-vinyl alcohol copolymer depends on the dense hydrogen bond network formed by the hydroxyl groups in the molecular chain. However, the hydroxyl groups have strong hydrophilicity, and in a high-humidity environment, water molecules will combine with the hydroxyl groups, disrupting the hydrogen bond network and causing a sharp increase in oxygen transmission rate, directly causing the softening of pharmaceutical products due to moisture absorption and the oxidative degradation of active pharmaceutical ingredients. However, after the introduction of ester groups, the hydrophobicity of the ester groups can replace some of the hydroxyl groups, reducing the interaction between water molecules and ethylene-vinyl alcohol copolymer and improving water resistance and barrier stability in a high-humidity environment. The spatial structure of the acetic ester group is more flexible, which can weaken the hydrogen bond force between the molecular chains of ethylene-vinyl alcohol copolymer, increase the chain segment mobility, improve the mechanical toughness, and reduce the risk of damage during processing and transportation. The ester group has better resistance to acidic substances than the hydroxyl group and will not undergo proton exchange to cause degradation, enhancing the chemical resistance. The introduction of ester groups can improve the compatibility of ethylene-vinyl alcohol copolymer with other layers, optimize the interlayer adhesion, and ensure the sealing integrity of the multi-layer composite film. The modified middle layer has excellent chemical stability and no safety risks, and is suitable for pharmaceutical contact requirements. DETAILED DESCRIPTION

[0026] The technical solutions in the embodiments of the present application will be clearly and completely described below in combination with the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative labor fall within the scope of the present application.

[0027] Embodiment 1 The present embodiment is a preparation method of a high molecular composite film for pharmaceutical products, comprising the following steps: Step s1: 100g of mica powder (the particle size of the mica powder is 500 mesh), 200mL of a coupling agent solution (the coupling agent solution is a solution prepared by mixing a coupling agent KH-550 and anhydrous ethanol in a volume ratio of 1:10) are added to a three-necked flask equipped with a stirrer, a thermometer, and a gas inlet tube, nitrogen is introduced for protection, and stirring is carried out at a temperature of 25℃ and a stirring speed of 250r / min for 2h, then the product is placed in a vacuum drying oven and dried at a temperature of 55℃ for 4h, then it is crushed by a planetary ball mill at a speed of 470r / min for 10min, and sieved through a 200 mesh sieve to obtain modified mica powder; Step s2: 15 mL of coupling agent KH-570 was dissolved in 300 mL of anhydrous ethanol, ultrasonic dispersion was carried out for 5 min under the condition of power of 280 W, then 50 g of nano-silica (particle size of nano-silica was 10 nm) was added, and placed in an ultrasonic cleaner, ultrasonic treatment was carried out for 1 h under the condition of temperature of 37 ℃ and power of 480 W, then placed in a vacuum drying oven, dried for 6 h under the condition of temperature of 75 ℃, dispersed by a high-speed dispersion machine under the condition of rotating speed of 9000 r / min for 5 min, to obtain modified nano-silica; Step s3: 92 g of low-density polyethylene (low-density polyethylene was Lanzhou Petrochemical brand LD26D), 5 g of modified mica powder and 2 g of modified nano-silica were vacuum dried at a temperature of 75 ℃ for 2 h, then blended and granulated by using a double-screw extruder, then blown into a film in a film blowing machine, to obtain a modified inner layer film; Step s4: 10 g of ethylene-vinyl alcohol copolymer (ethylene-vinyl alcohol copolymer brand was Japan Kao Lai EVALF101B) was placed in a vacuum drying oven, dried for 9 h under the condition of temperature of 75 ℃, then transferred to a four-necked flask equipped with a stirrer, a thermometer, a spherical condenser and a dropping funnel, 80 mL of anhydrous ethanol was added, stirred for 2 h under the condition of temperature of 55 ℃ and stirring speed of 150 r / min, 0.01 g of antioxidant 1010 and 10 mL of catalyst (the catalyst was a solution of p-toluenesulfonic acid and anhydrous ethanol mixed in a ratio of 0.05 g:10 mL) were added and stirred for 5 min, then the four-necked flask was placed in a constant-temperature water bath, heated to 70 ℃, 1.2 mL of acetic anhydride was added dropwise under the condition of stirring speed of 200 r / min, the dropping rate was controlled to be 1 drop / s, after the addition was completed, the temperature was maintained at 68 ℃ for 3 h, after the reaction was completed, the temperature of the flask was reduced to 40 ℃, a 4% sodium hydroxide solution was added dropwise, the dropping rate was controlled to be 1 drop / s, and the addition was stopped until pH=7, and stirring was continued for 30 min, then transferred to a separatory funnel, washed with purified water, oscillated for 10 min, then separated, the lower layer of salt water was removed, the water washing operation was repeated for 3 times, then transferred to a rotary evaporator, evaporated for 3 h under the condition of temperature of 45 ℃ and rotating speed of 75 r / min, then placed in a vacuum drying oven, dried for 7 h under the condition of temperature of 55 ℃, then crushed by a high-speed crusher, passed through an 80-mesh sieve, then cast into a film by using a single-screw casting machine, to obtain a modified middle layer film; Step s5: Place the polypropylene (medical grade, Yanshan Petrochemical, model K4912) in a vacuum drying oven and dry it at 75℃ for 4 hours. Then, feed it into a single-screw extruder. After extrusion, press it into a thick sheet by cooling rollers. Feed the thick sheet into a longitudinal stretching machine. The preheating temperature is 120℃, the stretching temperature is 135℃, and the stretching ratio is 3.5 times. After stretching, cool it to 40℃. Feed the longitudinally stretched film into a transverse stretching machine. The preheating temperature is 140℃, the stretching temperature is 155℃, the stretching ratio is 7 times, and the heat setting temperature is 160℃. After cooling to 40℃, feed it into a corona treatment machine with a processing power of 30W and a processing speed of 8m / min to make the film surface tension reach ≥40mN / m to obtain the outer film. Step s6: Place 10 mL of two-component polyurethane adhesive (the two-component polyurethane adhesive is Henkel LOCTITELIOFOL LA 7835 / LA 6256) and mixed solvent (the mixed solvent is a mixture of ethyl acetate and butanone in a volume ratio of 3:1) in a sealed container, stir for 15 min at a stirring speed of 450 r / min, and let stand for 30 min to remove bubbles to obtain the adhesive. Step s7: Perform corona treatment on one side of the modified inner layer film. The treatment power is 30W, the treatment speed is 5m / min, and the surface tension is ≥38mN / m to obtain the pretreated inner layer film. Step s8: Corona treatment is performed on both sides of the modified interlayer membrane. First side: power is 25W, speed is 5m / min, surface tension is ≥36mN / m; Second side: power is 30W, speed is 5m / min, surface tension is ≥38mN / m, to obtain the pretreated interlayer membrane. Step s9: Install the pretreated interlayer film at the unwinding station of the laminating machine with its first side facing upwards, and set the coating amount of the coating roller to 3.0 g / m. 2 Ensure that the adhesive is applied to the first side of the pretreated intermediate layer film. Adjust the lamination parameters: lamination temperature is 65℃, lamination pressure is 0.35MPa, and lamination speed is 5m / min. Place the pretreated inner layer film with the corona-faced side down and bond it to the pretreated intermediate layer film after adhesive application using a lamination roller. Then, roll it up to obtain a double-layer composite film. Step s10: Unwind the double-layer film so that the second side of the pretreated middle layer film faces upwards, and apply adhesive as well, with an adhesive application amount of 2.5 g / m. 2 The composite parameters were adjusted to a composite temperature of 60℃, a composite pressure of 0.3MPa, and a composite speed of 4m / min. The outer layer film with the corona-treated side facing down was bonded to the double-layer film after coating. The film was then rolled up and placed in a curing chamber at 40℃ for 48 hours to obtain a polymer composite film.

[0028] Example 2: This embodiment describes a method for preparing a polymer composite membrane for pharmaceutical use, comprising the following steps: Step s1: Add 105g of mica powder (mica powder particle size of 700 mesh) and 210mL of coupling agent solution (coupling agent solution is a mixture of coupling agent KH-550 and anhydrous ethanol at a volume ratio of 1:10) to a three-necked flask equipped with a stirrer, thermometer and gas delivery tube. Purge with nitrogen for protection and stir at 27℃ and 270r / min for 2.5h. Then place in a vacuum drying oven and dry at 57℃ for 4.5h. After that, pulverize with a planetary ball mill at 490r / min for 11min and pass through a 200-mesh sieve to obtain modified mica powder. Step s2: Dissolve 16 mL of coupling agent KH-570 in 310 mL of anhydrous ethanol and ultrasonically disperse for 6 min at a power of 290 W. Then add 53 g of nano silica (the particle size of nano silica is 15 nm), place it in an ultrasonic cleaner, and ultrasonically treat it for 1.5 h at a temperature of 38 °C and a power of 490 W. Then place it in a vacuum drying oven and dry it for 6.5 h at a temperature of 77 °C. Disperse it for 6 min at a speed of 9500 r / min using a high-speed disperser to obtain modified nano silica. Step s3: 137g of low-density polyethylene (Low-density polyethylene is Lanzhou Petrochemical brand LD26D), 7g of modified mica powder and 3g of modified nano silica were vacuum dried at 77℃ for 2.5h. Then, they were blended and granulated using a twin-screw extruder, and then blown into film in a blown film machine to obtain a modified inner layer film. Step s4: Place 11g of ethylene-vinyl alcohol copolymer (ethylene-vinyl alcohol copolymer brand name: Kuraray EVALF101B) in a vacuum drying oven and dry at 77℃ for 9.5h. Then transfer it to a four-necked flask equipped with a stirrer, thermometer, spherical condenser and dropping funnel, add 88mL of anhydrous ethanol, and stir at 58℃ and a stirring rate of 180r / min for 2.5h. Add 0.015g of antioxidant 1010 and 11mL of catalyst (catalyst is a solution of p-toluenesulfonic acid and anhydrous ethanol mixed at a ratio of 0.05g:10mL) and stir for 6min. Then place the four-necked flask in a constant temperature water bath, heat to 70℃, and stir at a stirring rate of 230r / min. 1.3 mL of acetic anhydride was added dropwise, with a dropping rate of 1 drop / s. After the addition was complete, the reaction was maintained at a constant temperature of 69 °C for 3 hours. After the reaction was completed, the temperature of the flask was lowered to 40 °C, and a 4% sodium hydroxide solution was added dropwise, with a dropping rate of 1 drop / s, until the pH reached 7. The addition was then stopped, and the mixture was stirred for 33 minutes. The mixture was then transferred to a separatory funnel, washed with purified water, shaken for 11 minutes, and allowed to stand to separate into layers. The lower layer of brine was removed, and the washing operation was repeated 4 times. The mixture was then transferred to a rotary evaporator and evaporated at 47 °C and a rotation speed of 77 r / min for 3.5 hours. After that, it was placed in a vacuum drying oven and dried at 57 °C for 8 hours. The mixture was then pulverized with a high-speed pulverizer, passed through an 80-mesh sieve, and then cast into a film using a single-screw casting machine to obtain a modified middle layer film. Step s5: Place the polypropylene (medical grade, Yanshan Petrochemical, model K4912) in a vacuum drying oven and dry it at 77℃ for 4.5 hours. Then, feed it into a single-screw extruder. After extrusion, press it into a thick sheet by cooling rollers. Feed the thick sheet into a longitudinal stretching machine. The preheating temperature is 125℃, the stretching temperature is 140℃, and the stretching ratio is 4 times. After stretching, cool it to 40℃. Feed the longitudinally stretched film into a transverse stretching machine. The preheating temperature is 145℃, the stretching temperature is 160℃, the stretching ratio is 7 times, and the heat setting temperature is 165℃. After cooling to 40℃, feed it into a corona treatment machine with a processing power of 35W and a processing speed of 9m / min to make the film surface tension reach ≥40mN / m to obtain the outer film. Step s6: Place 15 mL of two-component polyurethane adhesive (the two-component polyurethane adhesive is Henkel LOCTITELIOFOL LA 7835 / LA 6256) and 30 mL of mixed solvent (the mixed solvent is a solvent composed of ethyl acetate and butanone in a volume ratio of 3:1) in a sealed container, stir for 16 min at a stirring speed of 470 r / min, and let stand for 31 min to remove bubbles to obtain the adhesive. Step s7: One side of the modified inner layer film is subjected to corona treatment with a treatment power of 33W, a treatment speed of 5.5m / min, and a surface tension of ≥38mN / m to obtain the pretreated inner layer film; Step s8: Corona treatment is performed on both sides of the modified interlayer membrane. First side: power is 27W, speed is 5.5m / min, surface tension is ≥36mN / m; Second side: power is 33W, speed is 5.5m / min, surface tension is ≥38mN / m, to obtain the pretreated interlayer membrane. Step s9: Install the pretreated interlayer film at the unwinding station of the laminating machine with its first side facing upwards, and set the coating amount of the coating roller to 3.3 g / m. 2 Ensure that the adhesive is applied to the first side of the pretreated intermediate layer film. Adjust the lamination parameters: lamination temperature is 67℃, lamination pressure is 0.37MPa, and lamination speed is 5.5m / min. Place the pretreated inner layer film with the corona-faced side down and bond it to the pretreated intermediate layer film after adhesive application using a lamination roller. Then, roll it up to obtain a double-layer composite film. Step s10: Unwind the double-layer film so that the second side of the pretreated middle layer film faces upwards, and apply adhesive as well, with an adhesive application amount of 2.7 g / m. 2 The composite parameters were adjusted to a composite temperature of 63℃, a composite pressure of 0.33MPa, and a composite speed of 4.5m / min. The outer layer film with the corona-treated side facing down was bonded to the double-layer film after coating, and then rolled up. The three-layer composite film was placed in a curing chamber at 43℃ and cured for 48 hours to obtain a polymer composite film.

[0029] Example 3: This embodiment describes a method for preparing a polymer composite membrane for pharmaceutical use, comprising the following steps: Step s1: Add 110g of mica powder (mica powder with a particle size of 1000 mesh) and 220mL of coupling agent solution (coupling agent solution is a mixture of coupling agent KH-550 and anhydrous ethanol at a volume ratio of 1:10) to a three-necked flask equipped with a stirrer, thermometer and gas delivery tube. Purge with nitrogen for protection and stir at 30℃ and 300r / min for 3h. Then place in a vacuum drying oven and dry at 60℃ for 5h. After that, pulverize with a planetary ball mill at 500r / min for 12min and pass through a 200-mesh sieve to obtain modified mica powder. Step s2: Dissolve 17 mL of coupling agent KH-570 in 330 mL of anhydrous ethanol and ultrasonically disperse for 7 min at a power of 300 W. Then add 55 g of nano silica (nano silica with a particle size of 20 nm), place it in an ultrasonic cleaner, and ultrasonically treat it for 2 h at a temperature of 40 °C and a power of 500 W. Then place it in a vacuum drying oven and dry it for 7 h at a temperature of 80 °C. Disperse it for 7 min at a speed of 10000 r / min using a high-speed disperser to obtain modified nano silica. Step s3: 184g of low-density polyethylene (Low-density polyethylene is Lanzhou Petrochemical brand LD26D), 10g of modified mica powder and 4g of modified nano silica were vacuum dried at 80℃ for 3h. Then, they were blended and granulated using a twin-screw extruder, and then blown into a film in a blown film machine to obtain a modified inner layer film. Step s4: Place 12g of ethylene-vinyl alcohol copolymer (ethylene-vinyl alcohol copolymer brand name: Kuraray EVALF101B) in a vacuum drying oven and dry at 80℃ for 10h. Then transfer it to a four-necked flask equipped with a stirrer, thermometer, spherical condenser, and dropping funnel. Add 95mL of anhydrous ethanol and stir at 60℃ and a stirring rate of 200r / min for 3h. Add 0.02g of antioxidant 1010 and 12mL of catalyst (catalyst is a solution of p-toluenesulfonic acid and anhydrous ethanol mixed at a ratio of 0.05g:10mL) and stir for 7min. Then place the four-necked flask in a constant temperature water bath and heat to 70℃. Stir at a stirring rate of 250r / min. Add 1.4 mL of acetic anhydride dropwise, controlling the dropping rate at 2 drops / s. After the addition is complete, maintain a constant temperature of 70℃ for 3 hours. After the reaction is complete, lower the temperature of the flask to 40℃ and add 4% sodium hydroxide solution dropwise, controlling the dropping rate at 2 drops / s, until the pH=7 and stop adding. Continue stirring for 35 minutes, then transfer to a separatory funnel, wash with purified water, shake for 12 minutes, and allow to stand to separate into layers. Remove the lower salt layer and repeat the washing operation 5 times. Then transfer to a rotary evaporator and evaporate for 4 hours at 50℃ and 80 r / min. Then place in a vacuum drying oven and dry at 60℃ for 9 hours. Then pulverize with a high-speed pulverizer, pass through an 80-mesh sieve, and then cast into a film using a single-screw casting machine to obtain a modified middle layer film. Step s5: Place the polypropylene (medical grade, Yanshan Petrochemical, model K4912) in a vacuum drying oven and dry it at 80℃ for 5 hours. Then, feed it into a single-screw extruder. After extrusion, press it into a thick sheet by a cooling roller. Feed the thick sheet into a longitudinal stretching machine. The preheating temperature is 130℃, the stretching temperature is 145℃, and the stretching ratio is 4.5 times. After stretching, cool it to 40℃. Feed the longitudinally stretched film into a transverse stretching machine. The preheating temperature is 150℃, the stretching temperature is 165℃, the stretching ratio is 8 times, and the heat setting temperature is 170℃. After cooling to 40℃, feed it into a corona treatment machine with a processing power of 40W and a processing speed of 10m / min to make the film surface tension reach ≥40mN / m, thus obtaining the outer film. Step s6: Place 20 mL of two-component polyurethane adhesive (the two-component polyurethane adhesive is Henkel LOCTITELIOFOL LA 7835 / LA 6256) and 40 mL of mixed solvent (the mixed solvent is a mixture of ethyl acetate and butanone in a volume ratio of 3:1) in a sealed container, stir for 17 min at a stirring speed of 500 r / min, and let stand for 32 min to remove bubbles to obtain the adhesive. Step s7: Perform corona treatment on one side of the modified inner layer film with a treatment power of 35W, a treatment speed of 6m / min, and a surface tension of ≥38mN / m to obtain the pretreated inner layer film; Step s8: Corona treatment is performed on both sides of the modified interlayer membrane. First side: power is 30W, speed is 6m / min, surface tension is ≥36mN / m; Second side: power is 35W, speed is 6m / min, surface tension is ≥38mN / m, to obtain the pretreated interlayer membrane. Step s9: Install the pretreated interlayer film at the unwinding station of the laminating machine with its first side facing upwards, and set the coating amount of the coating roller to 3.5 g / m. 2 Ensure that the adhesive is applied to the first side of the pretreated intermediate layer film. Adjust the lamination parameters: lamination temperature is 70℃, lamination pressure is 0.4MPa, and lamination speed is 6m / min. Place the pretreated inner layer film with the corona-faced side down and bond it to the pretreated intermediate layer film after adhesive application using a lamination roller. Then, roll it up to obtain a double-layer composite film. Step s10: Unwind the double-layer film so that the second side of the pretreated middle layer is facing upwards, and apply adhesive as well, with an adhesive application amount of 3.0 g / m. 2 The composite parameters were adjusted to a composite temperature of 65℃, a composite pressure of 0.35MPa, and a composite speed of 5m / min. The outer layer film with the corona-treated side facing down was bonded to the double-layer film after coating, and then rolled up. The three-layer composite film was placed in a curing chamber at 45℃ and cured for 48 hours to obtain a polymer composite film.

[0030] Comparative Example 1: This comparative example illustrates a method for preparing a pharmaceutical polymer composite membrane, comprising the following steps: Step s1: 184g of low-density polyethylene (LD26D from Lanzhou Petrochemical) was vacuum dried at 80℃ for 3h, then blended and granulated using a twin-screw extruder, and then blown into a film in a blown film machine to obtain a modified inner layer film. Step s2: Place 12g of ethylene-vinyl alcohol copolymer (ethylene-vinyl alcohol copolymer brand name: Kuraray EVALF101B) in a vacuum drying oven and dry at 80℃ for 10h. Then transfer it to a four-necked flask equipped with a stirrer, thermometer, spherical condenser and dropping funnel, add 95mL of anhydrous ethanol, and stir at 60℃ and a stirring rate of 200r / min for 3h. Add 0.02g of antioxidant 1010 and 12mL of catalyst (catalyst is a solution of p-toluenesulfonic acid and anhydrous ethanol mixed at a ratio of 0.05g:10mL) and stir for 7min. Then place the four-necked flask in a constant temperature water bath, heat to 70℃, and stir continuously at a stirring rate of 250r / min. Add 1.4 mL of acetic anhydride dropwise, controlling the dropping rate at 2 drops / s. After the addition is complete, maintain a constant temperature of 70℃ for 3 hours. After the reaction is complete, lower the temperature of the flask to 40℃ and add 4% sodium hydroxide solution dropwise, controlling the dropping rate at 2 drops / s, until the pH=7 and stop adding. Continue stirring for 35 minutes, then transfer to a separatory funnel, wash with purified water, shake for 12 minutes, and allow to stand to separate into layers. Remove the lower salt layer and repeat the washing operation 5 times. Then transfer to a rotary evaporator and evaporate for 4 hours at 50℃ and 80 r / min. Then place in a vacuum drying oven and dry at 60℃ for 9 hours. Then pulverize with a high-speed pulverizer, pass through an 80-mesh sieve, and then cast into a film using a single-screw casting machine to obtain a modified middle layer film. Step s3: Place the polypropylene (medical grade, Yanshan Petrochemical, model K4912) in a vacuum drying oven and dry it at 80℃ for 5 hours. Then, feed it into a single-screw extruder. After extrusion, press it into a thick sheet through a cooling roller. Feed the thick sheet into a longitudinal stretching machine. The preheating temperature is 130℃, the stretching temperature is 145℃, and the stretching ratio is 4.5 times. After stretching, cool it to 40℃. Feed the longitudinally stretched film into a transverse stretching machine. The preheating temperature is 150℃, the stretching temperature is 165℃, the stretching ratio is 8 times, and the heat setting temperature is 170℃. After cooling to 40℃, feed it into a corona treatment machine with a processing power of 40W and a processing speed of 10m / min to make the film surface tension reach ≥40mN / m, thus obtaining the outer film. Step s4: Place 20 mL of two-component polyurethane adhesive (the two-component polyurethane adhesive is Henkel LOCTITELIOFOL LA 7835 / LA 6256) and 40 mL of mixed solvent (the mixed solvent is a mixture of ethyl acetate and butanone in a volume ratio of 3:1) in a sealed container, stir for 17 min at a stirring speed of 500 r / min, and let stand for 32 min to remove bubbles to obtain the adhesive. Step s5: Perform corona treatment on one side of the modified inner layer film. The treatment power is 35W, the treatment speed is 6m / min, and the surface tension is ≥38mN / m to obtain the pretreated inner layer film. Step s6: Corona treatment is performed on both sides of the modified interlayer membrane. First side: power is 30W, speed is 6m / min, surface tension is ≥36mN / m; Second side: power is 35W, speed is 6m / min, surface tension is ≥38mN / m, to obtain the pretreated interlayer membrane. Step s7: Install the pretreated interlayer film at the unwinding station of the laminating machine with its first side facing upwards, and set the coating amount of the coating roller to 3.5 g / m. 2 Ensure that the adhesive is applied to the first side of the pretreated intermediate layer film. Adjust the lamination parameters: lamination temperature is 70℃, lamination pressure is 0.4MPa, and lamination speed is 6m / min. Place the pretreated inner layer film with the corona-faced side down and bond it to the pretreated intermediate layer film after adhesive application using a lamination roller. Then, roll it up to obtain a double-layer composite film. Step s8: Unwind the double-layer film so that the second side of the pretreated middle layer film faces upwards, and apply adhesive as well, with an adhesive application amount of 3.0 g / m. 2 The composite parameters were adjusted to a composite temperature of 65℃, a composite pressure of 0.35MPa, and a composite speed of 5m / min. The outer layer film with the corona-treated side facing down was bonded to the double-layer film after coating, and then rolled up. The three-layer composite film was placed in a curing chamber at 45℃ and cured for 48 hours to obtain a polymer composite film.

[0031] Comparative Example 2: This comparative example illustrates a method for preparing a pharmaceutical polymer composite membrane, comprising the following steps: Step s1: Add 110g of mica powder (mica powder with a particle size of 1000 mesh) and 220mL of coupling agent solution (coupling agent solution is a mixture of coupling agent KH-550 and anhydrous ethanol at a volume ratio of 1:10) to a three-necked flask equipped with a stirrer, thermometer and gas delivery tube. Purge with nitrogen for protection and stir at 30℃ and 300r / min for 3h. Then place in a vacuum drying oven and dry at 60℃ for 5h. After that, pulverize with a planetary ball mill at 500r / min for 12min and pass through a 200-mesh sieve to obtain modified mica powder. Step s2: Dissolve 17 mL of coupling agent KH-570 in 330 mL of anhydrous ethanol and ultrasonically disperse for 7 min at a power of 300 W. Then add 55 g of nano silica (nano silica with a particle size of 20 nm), place it in an ultrasonic cleaner, and ultrasonically treat it for 2 h at a temperature of 40 °C and a power of 500 W. Then place it in a vacuum drying oven and dry it for 7 h at a temperature of 80 °C. Disperse it for 7 min at a speed of 10000 r / min using a high-speed disperser to obtain modified nano silica. Step s3: 184g of low-density polyethylene (Low-density polyethylene is Lanzhou Petrochemical brand LD26D), 10g of modified mica powder and 4g of modified nano silica were vacuum dried at 80℃ for 3h. Then, they were blended and granulated using a twin-screw extruder, and then blown into a film in a blown film machine to obtain a modified inner layer film. Step s4: Place 12g of ethylene-vinyl alcohol copolymer (ethylene-vinyl alcohol copolymer brand name is Kuraray EVALF101B from Japan) in a vacuum drying oven and dry it at 80℃ for 10h. Then, pulverize it with a high-speed pulverizer, pass it through an 80-mesh sieve, and then cast it into a film using a single screw casting machine to obtain a modified middle layer film. Step s5: Place the polypropylene (medical grade, Yanshan Petrochemical, model K4912) in a vacuum drying oven and dry it at 80℃ for 5 hours. Then, feed it into a single-screw extruder. After extrusion, press it into a thick sheet by a cooling roller. Feed the thick sheet into a longitudinal stretching machine. The preheating temperature is 130℃, the stretching temperature is 145℃, and the stretching ratio is 4.5 times. After stretching, cool it to 40℃. Feed the longitudinally stretched film into a transverse stretching machine. The preheating temperature is 150℃, the stretching temperature is 165℃, the stretching ratio is 8 times, and the heat setting temperature is 170℃. After cooling to 40℃, feed it into a corona treatment machine with a processing power of 40W and a processing speed of 10m / min to make the film surface tension reach ≥40mN / m, thus obtaining the outer film. Step s6: Place 20 mL of two-component polyurethane adhesive (the two-component polyurethane adhesive is Henkel LOCTITELIOFOL LA 7835 / LA 6256) and 40 mL of mixed solvent (the mixed solvent is a mixture of ethyl acetate and butanone in a volume ratio of 3:1) in a sealed container, stir for 17 min at a stirring speed of 500 r / min, and let stand for 32 min to remove bubbles to obtain the adhesive. Step s7: Perform corona treatment on one side of the modified inner layer film with a treatment power of 35W, a treatment speed of 6m / min, and a surface tension of ≥38mN / m to obtain the pretreated inner layer film; Step s8: Corona treatment is performed on both sides of the modified interlayer membrane. First side: power is 30W, speed is 6m / min, surface tension is ≥36mN / m; Second side: power is 35W, speed is 6m / min, surface tension is ≥38mN / m, to obtain the pretreated interlayer membrane. Step s9: Install the pretreated interlayer film at the unwinding station of the laminating machine with its first side facing upwards, and set the coating amount of the coating roller to 3.5 g / m. 2 Ensure that the adhesive is applied to the first side of the pretreated intermediate layer film. Adjust the lamination parameters: lamination temperature is 70℃, lamination pressure is 0.4MPa, and lamination speed is 6m / min. Place the pretreated inner layer film with the corona-faced side down and bond it to the pretreated intermediate layer film after adhesive application using a lamination roller. Then, roll it up to obtain a double-layer composite film. Step s10: Unwind the double-layer film so that the second side of the pretreated middle layer is facing upwards, and apply adhesive as well, with an adhesive application amount of 3.0 g / m. 2 The composite parameters were adjusted to a composite temperature of 65℃, a composite pressure of 0.35MPa, and a composite speed of 5m / min. The outer layer film with the corona-treated side facing down was bonded to the double-layer film after coating, and then rolled up. The three-layer composite film was placed in a curing chamber at 45℃ and cured for 48 hours to obtain a polymer composite film.

[0032] Comparative Example 3: This comparative example illustrates a method for preparing a pharmaceutical polymer composite membrane, comprising the following steps: Step s1: 184g of low-density polyethylene (LD26D from Lanzhou Petrochemical) was vacuum dried at 80℃ for 3h, then blended and granulated using a twin-screw extruder, and then blown into a film in a blown film machine to obtain a modified inner layer film. Step s2: Place 12g of ethylene-vinyl alcohol copolymer (ethylene-vinyl alcohol copolymer brand name is Kuraray EVALF101B from Japan) in a vacuum drying oven and dry it at 80℃ for 10h. Then, pulverize it with a high-speed pulverizer, pass it through an 80-mesh sieve, and then cast it into a film using a single screw casting machine to obtain a modified middle layer film. Step s3: Place the polypropylene (medical grade, Yanshan Petrochemical, model K4912) in a vacuum drying oven and dry it at 80℃ for 5 hours. Then, feed it into a single-screw extruder. After extrusion, press it into a thick sheet through a cooling roller. Feed the thick sheet into a longitudinal stretching machine. The preheating temperature is 130℃, the stretching temperature is 145℃, and the stretching ratio is 4.5 times. After stretching, cool it to 40℃. Feed the longitudinally stretched film into a transverse stretching machine. The preheating temperature is 150℃, the stretching temperature is 165℃, the stretching ratio is 8 times, and the heat setting temperature is 170℃. After cooling to 40℃, feed it into a corona treatment machine with a processing power of 40W and a processing speed of 10m / min to make the film surface tension reach ≥40mN / m, thus obtaining the outer film. Step s4: Place 20 mL of two-component polyurethane adhesive (the two-component polyurethane adhesive is Henkel LOCTITELIOFOL LA 7835 / LA 6256) and 40 mL of mixed solvent (the mixed solvent is a solvent composed of ethyl acetate and butanone in a volume ratio of 3:1) in a sealed container, stir for 17 min at a stirring speed of 500 r / min, and let stand for 32 min to remove bubbles to obtain the adhesive. Step s5: Perform corona treatment on one side of the modified inner layer film. The treatment power is 35W, the treatment speed is 6m / min, and the surface tension is ≥38mN / m to obtain the pretreated inner layer film. Step s6: Corona treatment is performed on both sides of the modified interlayer membrane. First side: power is 30W, speed is 6m / min, surface tension is ≥36mN / m; Second side: power is 35W, speed is 6m / min, surface tension is ≥38mN / m, to obtain the pretreated interlayer membrane. Step s7: Install the pretreated interlayer film at the unwinding station of the laminating machine with its first side facing upwards, and set the coating amount of the coating roller to 3.5 g / m. 2 Ensure that the adhesive is applied to the first side of the pretreated intermediate layer film. Adjust the lamination parameters: lamination temperature is 70℃, lamination pressure is 0.4MPa, and lamination speed is 6m / min. Place the pretreated inner layer film with the corona-faced side down and bond it to the pretreated intermediate layer film after adhesive application using a lamination roller. Then, roll it up to obtain a double-layer composite film. Step s8: Unwind the double-layer film so that the second side of the pretreated middle layer film faces upwards, and apply adhesive as well, with an adhesive application amount of 3.0 g / m. 2 The composite parameters were adjusted to a composite temperature of 65℃, a composite pressure of 0.35MPa, and a composite speed of 5m / min. The outer layer film with the corona-treated side facing down was bonded to the double-layer film after coating, and then rolled up. The three-layer composite film was placed in a curing chamber at 45℃ and cured for 48 hours to obtain a polymer composite film.

[0033] Performance testing

[0034] Examples 1-3 and Comparative Examples 1-3 were tested according to the following methods: Safety test: Take a 10cm×10cm membrane sample, soak it in 4% acetic acid and 50% ethanol at 60℃ for 2 hours, evaporate the soaking solution, weigh it, and calculate the migration amount.

[0035] Barrier performance test: Using an oxygen permeability meter, the test area was 50 cm² under conditions of 23°C and 65% relative humidity. 2 Nitrogen flow rate was 10 mL / min; oxygen permeability was tested using a water vapor permeability meter at 38℃ and 90% relative humidity over an area of ​​50 cm². 2 Test the water vapor transmission rate.

[0036] Mechanical property testing: Using an electronic tensile testing machine, the sample size is 150mm×15mm, the tensile speed is 50mm / min, and the tensile strength and elongation at break are tested; Using an electronic tensile testing machine, the T-strip method is adopted, the sample width is 15mm, the peeling speed is 300mm / min, and the composite strength of the inner layer-middle layer and the middle layer-outer layer interface is tested.

[0037] The test results are shown in the table below:

[0038] Referring to the table above, based on the comparison between Examples 1-3 and Comparative Examples 1-3, it can be seen that the polymer composite film meets the drug contact safety standards, has high oxygen and water vapor barrier properties, and has strong mechanical properties and good adaptability.

[0039] Based on the comparison between Example 3 and Comparative Example 1, it can be seen that the polymer composite film in Example 3 is obtained by compositing three layers of film: the inner layer is modified polyethylene, the middle layer is modified ethylene-vinyl alcohol copolymer, and the outer layer is polypropylene. The polymer composite film in Comparative Example 1 is also obtained by compositing three layers of film: the inner layer is polyethylene, the middle layer is modified ethylene-vinyl alcohol copolymer, and the outer layer is polypropylene. Therefore, the polymer composite film in Example 3 has better performance than the polymer composite film in Comparative Example 1. Based on the comparison between Example 3 and Comparative Example 2, it can be seen that the polymer composite film in Example 3 is obtained by compositing three layers of film: the inner layer is modified polyethylene, the middle layer is modified ethylene-vinyl alcohol copolymer, and the outer layer is polypropylene. The polymer composite film in Comparative Example 2 is also obtained by compositing three layers of film: the inner layer is modified polyethylene, the middle layer is ethylene-vinyl alcohol copolymer, and the outer layer is polypropylene. Therefore, the polymer composite film in Example 3 has better performance than the polymer composite film in Comparative Example 2. Based on the comparison between Example 3 and Comparative Example 3, it can be seen that the polymer composite membrane in Example 3 is obtained by compositing three layers of membrane: the inner layer is modified polyethylene, the middle layer is modified ethylene-vinyl alcohol copolymer, and the outer layer is polypropylene. The polymer composite membrane in Comparative Example 3 is also obtained by compositing three layers of membrane: the inner layer is polyethylene, the middle layer is ethylene-vinyl alcohol copolymer, and the outer layer is polypropylene. Therefore, the polymer composite membrane in Example 3 has better performance than the polymer composite membrane in Comparative Example 3.

[0040] In the description of this specification, references to terms such as "an embodiment," "example," "specific example," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0041] The above description is merely an example and illustration of the present invention. Those skilled in the art can make various modifications or additions to the specific embodiments described or use similar methods to replace them, as long as they do not deviate from the invention or exceed the scope defined in this application, they should all fall within the protection scope of the present invention.

Claims

1. A method for preparing a polymeric composite membrane for pharmaceutical use, characterized in that, Includes the following steps: Step 1: Stir the mica powder and coupling agent solution, dry, pulverize, and sieve to obtain modified mica powder; Step 2: Dissolve coupling agent KH-570 in anhydrous ethanol, disperse by ultrasonication, then add nano-silica, sonicate, dry, and disperse to obtain modified nano-silica; Step 3: Vacuum dry low-density polyethylene, modified mica powder and modified nano silica respectively, then blend and granulate them, blown into film to obtain modified inner layer film. Step 4: Dry the ethylene-vinyl alcohol copolymer, then transfer it to a four-necked flask, add anhydrous ethanol and stir, add antioxidant 1010 and catalyst and stir, add acetic anhydride and react at a constant temperature, cool down, add sodium hydroxide solution dropwise until pH=7 and stop adding, continue stirring, wash with water and filter, rotary evaporate, then dry, pulverize, sieve, and then cast into a film to obtain the modified middle layer film. Step 5: Dry the polypropylene, then add it to a single screw extruder for extrusion, roll it and send it to a longitudinal stretching machine for stretching, then send it to a transverse stretching machine for stretching, cool it, corona discharge it to obtain the outer film. Step 6: Stir the two-component polyurethane adhesive and mixed solvent, let it stand to remove bubbles, and obtain the adhesive. Step 7: Perform corona treatment on one side of the modified inner layer membrane to obtain the pretreated inner layer membrane; Step 8: Perform corona treatment on both sides of the modified interlayer membrane to obtain the pretreated interlayer membrane; Step 9: Apply adhesive to the pretreated middle layer film, and then bond the pretreated inner layer film and the pretreated middle layer film with adhesive through a composite roller to obtain a double-layer composite film. Step 10: Apply adhesive to the pretreated middle layer of the double-layer film with the second side facing up, and then bond the outer layer film with the corona-treated side facing down to the adhesive-coated double-layer film. Roll it up and cure it to obtain a polymer composite film.

2. The method for preparing a pharmaceutical polymer composite membrane according to claim 1, characterized in that, The ratio of mica powder to coupling agent solution in step one is 100-110g: 200-220mL.

3. The method for preparing a pharmaceutical polymer composite membrane according to claim 1, characterized in that, The coupling agent solution in step one is a solution of coupling agent KH-550 and anhydrous ethanol mixed in a volume ratio of 1:10; the mica powder has a particle size of 500-1000 mesh.

4. The method for preparing a pharmaceutical polymer composite membrane according to claim 1, characterized in that, In step two, the ratio of coupling agent KH-570, anhydrous ethanol, and nano silica is 15-17 mL: 300-330 mL: 50-55 g; the particle size of the nano silica is 10-20 nm.

5. The method for preparing a pharmaceutical polymer composite membrane according to claim 1, characterized in that, In step three, the ratio of low-density polyethylene, modified mica powder, and modified nano-silica is 92-184g: 5-10g: 2-4g.

6. The method for preparing a pharmaceutical polymer composite membrane according to claim 1, characterized in that, In step four, the ratio of the amount of ethylene-vinyl alcohol copolymer, anhydrous ethanol, antioxidant 1010, catalyst, and acetic anhydride is 10-12g: 80-95mL: 0.01-0.02g: 10-12mL: 1.2-1.4mL.

7. The method for preparing a pharmaceutical polymer composite membrane according to claim 1, characterized in that, The catalyst in step four is a solution of p-toluenesulfonic acid and anhydrous ethanol mixed in a ratio of 0.05 g: 10 mL; the sodium hydroxide solution has a mass fraction of 4%.

8. The method for preparing a pharmaceutical polymer composite membrane according to claim 1, characterized in that, In step six, the ratio of the two-component polyurethane adhesive to the mixed solvent is 10-20 mL: 1-2 mL: 20-40 mL.

9. The method for preparing a pharmaceutical polymer composite membrane according to claim 1, characterized in that, The mixed solvent in step six is ​​a solvent composed of ethyl acetate and butanone mixed in a volume ratio of 3:

1.

10. A polymeric composite membrane for pharmaceutical use, characterized in that, The polymer composite membrane is prepared by the method for preparing polymer composite membrane according to any one of claims 1-9.

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