Multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film and preparation method thereof

Abstract

The present invention relates to the technical field of composite film preparation, specifically to a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film and a preparation method thereof, comprising a substrate layer, a gas barrier layer, an adhesive transition layer, and a nano-ceramic functional coating; the substrate layer comprises the following components by mass: 80-100 parts of biaxially oriented polypropylene; 20-30 parts of metallocene linear low-density polyethylene; 5-8 parts of nano-titanium dioxide; 0.5-1 parts of β-(3,5-di-tert-butyl-4-hydroxyphenyl)propionic acid; and 0.3-0.6 parts of calcium stearate. The present invention utilizes multi-layer co-extrusion and gradient curing technology, a three-layer co-extrusion process to ensure uniform base film thickness and firm interlayer bonding, plasma surface treatment to enhance coating adhesion, and a segmented curing strategy for the nano-ceramic coating to ensure active retention and uniform distribution of functional components. Compared with the hot pressing composite or solvent coating processes of traditional composite films, the present invention significantly reduces energy consumption and the risk of solvent residue, while improving production efficiency and product consistency, providing large-scale application for pharmaceutical packaging.

Description

Technical Field

[0001] The present invention relates to the technical field of composite film preparation, in particular to a multi-layer co-extruded nano-ceramic coating high-barrier composite film for pharmaceutical packaging and a preparation method thereof. Background Art

[0002] Composite films are thin film structures formed by combining multiple layers of functional materials through precision processing technology. They are specifically designed to meet the stringent requirements of pharmaceutical packaging for high barrier properties, antimicrobial properties, and mechanical stability. Their core value lies in the synergistic effect of the various layers, effectively blocking external factors such as oxygen and water vapor while also inhibiting microbial contamination. They are widely used in applications such as vaccine vial stoppers, injection packaging, and biologics sealing, ensuring the safety and effectiveness of drugs during storage and transportation.

[0003] Traditional medical composite films are mostly made of simple composites of basic polymers such as polyethylene and polypropylene with aluminum foil or ordinary barrier layers (such as ethylene-vinyl alcohol copolymer). These materials have significant defects: the barrier performance is easily attenuated by humidity, the aluminum foil layer has poor flexibility and is easily corroded and perforated, and the lack of antibacterial function on the surface leads to the risk of microbial growth. In addition, insufficient bonding between layers can easily cause peeling, and high temperature and high pressure during processing may destroy active drug ingredients. These problems directly threaten the stability of drugs and even cause secondary pollution.

[0004] Based on this, the present invention provides a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film and a preparation method thereof to solve the above-mentioned technical problems. Summary of the Invention

[0005] The purpose of the present invention is to provide a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film and a preparation method thereof, so as to solve the problems mentioned in the above background technology.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] Multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film, including substrate layer, gas barrier layer, adhesive transition layer and nano-ceramic functional coating;

[0008] The substrate layer comprises the following components by mass: 80-100 parts of biaxially oriented polypropylene; 20-30 parts of metallocene linear low-density polyethylene; 5-8 parts of nano-titanium dioxide; 0.5-1 parts of β-(3,5-di-tert-butyl-4-hydroxyphenyl) propionic acid; and 0.3-0.6 parts of calcium stearate.

[0009] The gas barrier layer comprises the following components by mass: 40-60 parts of ethylene-vinyl alcohol copolymer; 15-25 parts of polyvinylidene chloride emulsion; 10-15 parts of nano boron nitride sheet; and 8-12 parts of modified montmorillonite.

[0010] The bonding transition layer comprises the following components by mass: maleic anhydride grafted polypropylene: 100 parts; nano silicon carbide whiskers: 3-5 parts;

[0011] The nano ceramic functional coating comprises the following components by mass: 8-12 parts of nano zinc oxide / silver composite particles; 5-8 parts of fumed silica; 2-4 parts of KH-550 silane coupling agent; 1-2 parts of polyhexamethylene biguanide hydrochloride; and 3-5 parts of perfluoroalkyl ethyl acrylate copolymer.

[0012] Preferably, the nano titanium dioxide is prepared by reacting tetrabutyl titanate in an acidic aqueous solution with a pH of 1-3 at 180-220° C. for 6-8 hours through a hydrothermal synthesis method, with a purity of ≥99.5% and a particle size of 20-50 nm.

[0013] Preferably, the nano boron nitride sheet is prepared by mixing boron powder and urea in a molar ratio of 1:3, reacting at 1200-1400° C. for 2-4 hours under an ammonia protective atmosphere by high-temperature vapor deposition, with a purity of ≥99.9% and a thickness of <10 nm.

[0014] Preferably, the modified montmorillonite is prepared by treating natural sodium montmorillonite and hexadecyltrimethylammonium bromide in a mass ratio of 1:0.5 in an aqueous solution at 60-80° C. through an ion exchange reaction for 12-24 hours, and the cation exchange capacity is ≥100 mmol / 100 g.

[0015] Preferably, the maleic anhydride grafted polypropylene is prepared by extruding and granulating isotactic polypropylene and maleic anhydride at a mass ratio of 100:5 at 180-200° C. by a melt grafting method in the presence of dicumyl peroxide initiator, with a grafting rate of 1.2-1.8%.

[0016] Preferably, the nano zinc oxide / silver composite particles are prepared by dissolving zinc nitrate and silver nitrate in a molar ratio of 10:1, generating a precursor by coprecipitation under alkaline conditions of pH = 10-12, and then calcining at 400-500° C. for 2 hours, with a silver loading of 8-12 wt%.

[0017] Preferably, the fumed silicon dioxide is produced by instantaneously reacting silicon tetrachloride with a hydrogen / oxygen mixed gas in a hydrogen-oxygen flame high-temperature hydrolysis reactor at 1200-1500°C, with a specific surface area of 200-400m 2 / g.

[0018] Preferably, the polyhexamethylene biguanide hydrochloride is prepared by polymerizing guanidine hydrochloride and hexamethylene diamine in a molar ratio of 1:1.2 at 140-160° C. for 4-6 hours under nitrogen protection through a condensation reaction, and the degree of polymerization n is 20-30.

[0019] Based on the above composite film formula, the present invention also proposes a method for preparing a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film, comprising the following steps:

[0020] S1. The following polymer particles are used for the substrate layer, barrier layer and adhesive layer:

[0021] Biaxially oriented polypropylene, metallocene linear low-density polyethylene, ethylene-vinyl alcohol copolymer, polyvinylidene chloride emulsion and maleic anhydride grafted polypropylene are placed in a vacuum dryer respectively and dried at 80-100°C for 4-6 hours to reduce the water content to ≤0.02%.

[0022] At the same time, nano-titanium dioxide, nano-boron nitride flakes, modified montmorillonite, and nano-silicon carbide whisker powder materials are placed in a nitrogen-protected ball mill and dispersed at a speed of 300-400 rpm for 30-60 minutes to ensure uniform particle size distribution;

[0023] S2. Use three-layer co-extrusion film blowing unit for melt co-extrusion:

[0024] Substrate layer: 80-100 parts of pretreated biaxially oriented polypropylene, 20-30 parts of metallocene linear low-density polyethylene, 5-8 parts of nano-titanium dioxide, 0.5-1 part of β-(3,5-di-tert-butyl-4-hydroxyphenyl) propionic acid, and 0.3-0.6 parts of calcium stearate are mixed and melt-extruded through a main extruder at 190-210°C;

[0025] Barrier layer: 40-60 parts of ethylene-vinyl alcohol copolymer, 15-25 parts of polyvinylidene chloride emulsion, 10-15 parts of nano-boron nitride sheet, and 8-12 parts of modified montmorillonite are extruded through a second extruder at 200-230°C;

[0026] Adhesive layer: Maleic anhydride grafted polypropylene: 100 parts and nano silicon carbide whiskers: 3-5 parts are melted at 180-200°C through a third extruder;

[0027] After the melt layers are compounded by the distributor, they are extruded from the annular die at a pressure of 0.8-1.2 MPa. The film bubble is cooled and shaped by the air ring. The winding speed is 8-12 m / min, and finally a three-layer composite base film with a total thickness of 80-120 μm is formed.

[0028] S3. The co-extruded base film is introduced into an atmospheric plasma treatment machine and corona treated in an oxygen / argon mixed gas environment with a treatment power density of 100-150 watts / m2 and a dwell time of 0.5-1.2 seconds to increase the surface tension to 50-55 mN / m and a dyne value ≥40;

[0029] After treatment, the basement membrane needs to be placed in a constant temperature and humidity chamber for 10-15 minutes to stabilize the surface state;

[0030] S4. Use a micro-gravure roll coater to evenly coat the nano-ceramic functional coating slurry on the surface of the base film:

[0031] Mix 8-12 parts of nano zinc oxide / silver composite particles, 5-8 parts of fumed silica, 2-4 parts of KH-550 silane coupling agent, 1-2 parts of polyhexamethylene biguanide hydrochloride, and 3-5 parts of perfluoroalkyl ethyl acrylate copolymer with anhydrous ethanol in a mass ratio of 1:4, and treat with an ultrasonic disperser for 30-40 minutes to form a stable suspension with a solid content of 20-25%;

[0032] Set the coating roller speed ratio to 1:1.2-1.5 and the base film tension to 8-10N / cm 2 , wet film thickness 10-15μm, after coating, the film material immediately enters the infrared pre-drying zone to make the solvent volatilization rate ≥85%;

[0033] S5. Place the film in a hot air circulation curing oven and cure it in three stages of gradient temperature increase. After curing, it is quickly cooled to room temperature using a cold roller. The final coating thickness is controlled at 2-3 μm.

[0034] S6. Finally, use a CNC slitting machine to cut the wide film into the specified width, with a slitting speed of 20-30 meters / minute and a tension control of 5-8N / cm 2 .

[0035] Preferably, the three stages of gradient temperature rise curing in step S5 are:

[0036] The first stage: keep warm at 80-100℃ for 2-3 minutes to promote cross-linking of silane coupling agent;

[0037] The second stage: treatment at 120-140°C for 5-8 minutes to achieve melt leveling of the perfluoroalkyl ethyl acrylate copolymer;

[0038] The third stage: rapid curing at 160-180℃ for 30-60 seconds to form a dense nano-ceramic coating.

[0039] Compared with the prior art, the present invention has the following beneficial effects:

[0040] The substrate layer of the present invention adopts biaxially oriented polypropylene and metallocene polyethylene to synergistically enhance the mechanical properties. The gas barrier layer introduces nano-boron nitride sheets and modified montmorillonite to construct a multi-level barrier network. The surface nano-ceramic coating integrates zinc oxide / silver composite particles and perfluoropolymers to give the membrane material self-cleaning and long-lasting antibacterial properties. It not only solves the defects of unstable barrier performance and easy contamination of traditional materials, but also avoids the imbalance between mechanical properties and flexibility through the precise dispersion of nano-fillers. At the same time, through multi-layer co-extrusion and gradient curing technology, the three-layer co-extrusion process ensures that the base film thickness is uniform and the interlayer bonding is firm. Plasma surface treatment enhances coating adhesion. The segmented curing strategy of the nano-ceramic coating ensures the active retention and uniform distribution of functional components. Compared with the hot pressing composite or solvent coating process of traditional composite films, it greatly reduces energy consumption and solvent residue risks, while improving production efficiency and product consistency, providing large-scale application for pharmaceutical packaging. DETAILED DESCRIPTION

[0041] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts shall fall within the scope of protection of the present invention.

[0042] 1. Materials:

[0043] The components of the multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film of the present invention are all commercially available unless otherwise specified.

[0044] The present invention provides a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film, comprising a substrate layer, a gas barrier layer, an adhesive transition layer and a nano-ceramic functional coating;

[0045] It should be noted that the substrate layer includes the following components by mass: biaxially oriented polypropylene: 80-100 parts; metallocene linear low-density polyethylene: 20-30 parts; nano titanium dioxide: 5-8 parts; β-(3,5-di-tert-butyl-4-hydroxyphenyl) propionic acid: 0.5-1 part; calcium stearate: 0.3-0.6 parts;

[0046] The gas barrier layer comprises the following components by mass: ethylene-vinyl alcohol copolymer: 40-60 parts; polyvinylidene chloride emulsion: 15-25 parts; nano boron nitride sheet: 10-15 parts; modified montmorillonite: 8-12 parts;

[0047] The bonding transition layer comprises the following components by mass: maleic anhydride grafted polypropylene: 100 parts; nano silicon carbide whiskers: 3-5 parts;

[0048] The nano ceramic functional coating comprises the following components by mass: 8-12 parts of nano zinc oxide / silver composite particles; 5-8 parts of fumed silica; 2-4 parts of KH-550 silane coupling agent; 1-2 parts of polyhexamethylene biguanide hydrochloride; and 3-5 parts of perfluoroalkyl ethyl acrylate copolymer.

[0049] It should be noted that nano titanium dioxide is prepared by hydrothermal synthesis of tetrabutyl titanate in an acidic aqueous solution with a pH of 1-3 at 180-220° C. for 6-8 hours, with a purity of ≥99.5% and a particle size of 20-50 nm.

[0050] It should also be noted that the nano boron nitride sheet is prepared by mixing boron powder and urea in a 1:3 molar ratio, and reacting them at 1200-1400°C for 2-4 hours under an ammonia protective atmosphere through high-temperature vapor deposition. The purity is ≥99.9% and the thickness is <10nm.

[0051] It should also be noted that the modified montmorillonite is prepared by treating natural sodium montmorillonite and hexadecyltrimethylammonium bromide in a mass ratio of 1:0.5 in an aqueous solution at 60-80°C through an ion exchange reaction for 12-24 hours, and the cation exchange capacity is ≥100mmol / 100g.

[0052] It should also be noted that the maleic anhydride grafted polypropylene is prepared by extruding and granulating isotactic polypropylene and maleic anhydride at a mass ratio of 100:5 at 180-200°C through a melt grafting method under the action of dicumyl peroxide initiator, with a grafting rate of 1.2-1.8%.

[0053] It should also be noted that the nano zinc oxide / silver composite particles are prepared by dissolving zinc nitrate and silver nitrate in a 10:1 molar ratio, generating a precursor by a coprecipitation method under alkaline conditions of pH = 10-12, and then calcining at 400-500°C for 2 hours, with a silver loading of 8-12 wt%.

[0054] Among them, it should be noted that fumed silica is produced by the instantaneous reaction of silicon tetrachloride and hydrogen / oxygen mixed gas at 1200-1500℃ in a hydrogen-oxygen flame high-temperature hydrolysis reactor, with a specific surface area of 200-400m 2 / g.

[0055] It should be noted that polyhexamethylene biguanide hydrochloride is prepared by polymerizing guanidine hydrochloride and hexamethylenediamine in a molar ratio of 1:1.2 at 140-160° C. for 4-6 hours under nitrogen protection through a condensation reaction, with a degree of polymerization n=20-30.

[0056] 2. Process:

[0057] Based on the above composite film formula, the present invention also proposes a method for preparing a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film, comprising the following steps:

[0058] S1. The following polymer particles are used for the substrate layer, barrier layer and adhesive layer:

[0059] Biaxially oriented polypropylene, metallocene linear low-density polyethylene, ethylene-vinyl alcohol copolymer, polyvinylidene chloride emulsion and maleic anhydride grafted polypropylene are placed in a vacuum dryer respectively and dried at 80-100°C for 4-6 hours to reduce the water content to ≤0.02%.

[0060] At the same time, nano-titanium dioxide, nano-boron nitride flakes, modified montmorillonite, and nano-silicon carbide whisker powder materials are placed in a nitrogen-protected ball mill and dispersed at a speed of 300-400 rpm for 30-60 minutes to ensure uniform particle size distribution;

[0061] S2. Use three-layer co-extrusion film blowing unit for melt co-extrusion:

[0062] Substrate layer: 80-100 parts of pretreated biaxially oriented polypropylene, 20-30 parts of metallocene linear low-density polyethylene, 5-8 parts of nano-titanium dioxide, 0.5-1 part of β-(3,5-di-tert-butyl-4-hydroxyphenyl) propionic acid, and 0.3-0.6 parts of calcium stearate are mixed and melt-extruded through a main extruder at 190-210°C;

[0063] Barrier layer: 40-60 parts of ethylene-vinyl alcohol copolymer, 15-25 parts of polyvinylidene chloride emulsion, 10-15 parts of nano-boron nitride sheet, and 8-12 parts of modified montmorillonite are extruded through a second extruder at 200-230°C;

[0064] Adhesive layer: Maleic anhydride grafted polypropylene: 100 parts and nano silicon carbide whiskers: 3-5 parts are melted at 180-200°C through a third extruder;

[0065] After the melt layers are compounded by the distributor, they are extruded from the annular die at a pressure of 0.8-1.2 MPa. The film bubble is cooled and shaped by the air ring. The winding speed is 8-12 m / min, and finally a three-layer composite base film with a total thickness of 80-120 μm is formed.

[0066] S3. The co-extruded base film is introduced into an atmospheric plasma treatment machine and corona treated in an oxygen / argon mixed gas environment with a treatment power density of 100-150 watts / m2 and a dwell time of 0.5-1.2 seconds to increase the surface tension to 50-55 mN / m and a dyne value ≥40;

[0067] After treatment, the basement membrane needs to be placed in a constant temperature and humidity chamber for 10-15 minutes to stabilize the surface state;

[0068] S4. Use a micro-gravure roll coater to evenly coat the nano-ceramic functional coating slurry on the surface of the base film:

[0069] Mix 8-12 parts of nano zinc oxide / silver composite particles, 5-8 parts of fumed silica, 2-4 parts of KH-550 silane coupling agent, 1-2 parts of polyhexamethylene biguanide hydrochloride, and 3-5 parts of perfluoroalkyl ethyl acrylate copolymer with anhydrous ethanol in a mass ratio of 1:4, and treat with an ultrasonic disperser for 30-40 minutes to form a stable suspension with a solid content of 20-25%;

[0070] Set the coating roller speed ratio to 1:1.2-1.5 and the base film tension to 8-10N / cm 2 , wet film thickness 10-15μm, after coating, the film material immediately enters the infrared pre-drying zone to make the solvent volatilization rate ≥85%;

[0071] S5. Place the film in a hot air circulation curing oven and cure it in three stages of gradient temperature increase. After curing, it is quickly cooled to room temperature using a cold roller. The final coating thickness is controlled at 2-3 μm.

[0072] S6. Finally, use a CNC slitting machine to cut the wide film into the specified width, with a slitting speed of 20-30 meters / minute and a tension control of 5-8N / cm 2 .

[0073] It should be noted that the three stages of gradient temperature rise and curing in step S5 are:

[0074] The first stage: keep warm at 80-100℃ for 2-3 minutes to promote cross-linking of silane coupling agent;

[0075] The second stage: treatment at 120-140°C for 5-8 minutes to achieve melt leveling of the perfluoroalkyl ethyl acrylate copolymer;

[0076] The third stage: rapid curing at 160-180℃ for 30-60 seconds to form a dense nano-ceramic coating.

[0077] Example 1: In this example, a method for preparing a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film comprises the following steps:

[0078] S1. Raw material pretreatment: The polymer particles were dried in a vacuum dryer at 90°C for 5 hours; the powder material was dispersed in a nitrogen-protected ball mill at 350 rpm for 45 minutes.

[0079] S2 co-extrusion: main extruder temperature 200 ℃, second extruder temperature 215 ℃, third extruder temperature 190 ℃; die pressure 1.0 MPa, wind ring wind speed 18 m / s, winding line speed 10 m / min;

[0080] S3. Plasma treatment: power density 125 W / m², dwell time 0.8 s;

[0081] S4 coating: slurry solid content 22.5%, coating roller speed ratio 1:1.3, pre-drying temperature 70 ° C;

[0082] S5. Gradient curing: first stage at 90°C for 2.5 minutes; second stage at 130°C for 6 minutes; third stage at 170°C for 45 seconds;

[0083] Example 2: The amount of nano-titanium dioxide is 8 parts, and the other process parameters and component parameters are the same as those in Example 1;

[0084] Example 3: The amount of the nano-boron nitride sheet is 15 parts, and the other process parameters and component parameters are the same as those in Example 1;

[0085] Example 4: The modified montmorillonite is 12 parts, and the other process parameters and component parameters are the same as those in Example 1;

[0086] Example 5: The amount of nano zinc oxide / silver composite particles is 12 parts, and the other process parameters and component parameters are the same as those in Example 1;

[0087] The component parameters in Examples 1 to 5 are shown in Table 1:

[0088] Material name Example 1 Example 2 Example 3 Example 4 Example 5 Biaxially oriented polypropylene 90 80 100 90 90 Metallocene linear low-density polyethylene 25 30 20 25 25 Nano-titanium dioxide 6 8 5 6 6 Nano-boron nitride sheets 12 10 15 12 12 Modified montmorillonite 10 8 12 10 10 Nano zinc oxide / silver composite particles 10 8 12 10 10

[0089] Table 1 Component parameters in Examples 1 to 5

[0090] Comparative Example 1: The amount of nano-titanium dioxide is 3 parts, which is lower than the lower limit of the interval. Other process parameters and component parameters are the same as those in Example 1.

[0091] Comparative Example 2: The amount of nano-titanium dioxide is 10 parts, which is higher than the upper limit of the range. Other process parameters and component parameters are the same as those in Example 1.

[0092] Comparative Example 3: The amount of the nano-boron nitride sheet is 18 parts, which is higher than the upper limit of the range. Other process parameters and component parameters are the same as those in Example 1.

[0093] Comparative Example 4: The modified montmorillonite was 5 parts, which was lower than the lower limit of the interval, and the other process parameters and component parameters were the same as those in Example 1;

[0094] Comparative Example 5: The amount of nano zinc oxide / silver composite particles was 5 parts, which was lower than the lower limit of the range. Other process parameters and component parameters were the same as those in Example 1.

[0095] The component parameters in Comparative Examples 1 to 5 are shown in Table 2:

[0096] Table 2 Component parameters of Comparative Examples 1 to 5

[0097] Material name Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Biaxially oriented polypropylene 90 90 90 90 90 Metallocene linear low-density polyethylene 25 25 25 25 25 Nano-titanium dioxide 3 10 6 6 6 Nano-boron nitride sheets 12 12 18 12 12 Modified montmorillonite 10 10 10 5 15 Nano zinc oxide / silver composite particles 10 10 10 10 5

[0098] 3. Performance test:

[0099] Composite film samples were prepared according to the embodiment and the comparative example, and the samples were tested for oxygen transmission rate, water vapor transmission rate, Escherichia coli inhibition rate and tensile strength, the steps of which are as follows:

[0100] a. Oxygen Transmission Rate (OTR) Test:

[0101] The standard is based on international standards: ISO15105-1 (differential pressure method) or ASTMD3985 (isobaric method), which measures the rate at which oxygen penetrates a unit area of film at constant temperature and humidity;

[0102] a1. Sample preparation:

[0103] Size: Circular specimen with a diameter of ≥100mm, uniform thickness and no defects;

[0104] Quantity: at least 3 parallel samples;

[0105] a2. Test conditions:

[0106] Temperature: 23±1°C; Relative humidity: 0%RH (dry method) or 50%RH (wet method);

[0107] a3. Equipment operation:

[0108] The sample was clamped in the test chamber, with pure oxygen (pressure 0.1 MPa) introduced into one side and nitrogen carrier gas into the other side;

[0109] Use a gas sensor to detect the amount of oxygen permeation and record stable data within 24 hours;

[0110] Result calculation: Oxygen transmission rate = permeation amount / (time × area × pressure difference), unit: cm 3 / (m 2 ·day·atm);

[0111] b. Water Vapor Transmission Rate (WVTR) Test:

[0112] The standard is based on international standards: ASTM E96 (cup method) or ISO 15106-3 (infrared sensor method), which measures the mass of water vapor passing through a unit area of film per unit time;

[0113] b1. Sample preparation:

[0114] Size: Circular specimen with a diameter of ≥70mm, with sealed edges and no leakage;

[0115] Quantity: at least 5 parallel samples;

[0116] b2. Test conditions:

[0117] Temperature: 38 ± 0.5°C; relative humidity gradient: 90% RH (inside) → 50% RH (outside);

[0118] b3. Equipment operation (cup method):

[0119] Seal the sample in a moisture-permeable cup filled with desiccant (anhydrous calcium chloride) and weigh it regularly;

[0120] Continue measuring until the weight change stabilizes (48-72 hours);

[0121] Result calculation: Water vapor transmission rate = (weight change × 24) / (time × area), unit: g / (m 2 day);

[0122] c. E. coli inhibition rate test:

[0123] The standard is based on the international standard: ISO22196 (Determination of antibacterial properties of plastic surfaces). The antibacterial effect is calculated by comparing the bacterial survival rate of the test sample with that of the control sample.

[0124] c1. Sample preparation:

[0125] Size: 50mm×50mm square specimen, thickness consistent with actual use;

[0126] Pretreatment: UV sterilization for 30 minutes;

[0127] c2. Bacterial liquid inoculation:

[0128] Escherichia coli (ATCC25922) suspension was used at a concentration of 1×10 5 ~5×10 5 CFU / mL;

[0129] Add 0.4 mL of bacterial solution to the sample surface and cover with polyethylene film to prevent evaporation;

[0130] c3. Culture conditions:

[0131] Temperature 37±1℃, humidity ≥90%, incubate for 24 hours;

[0132] c4. Colony count:

[0133] Elute the bacteria with neutralizing solution, spread on agar plates after dilution, and incubate at 37°C for 24 hours to count the colonies;

[0134] Calculation of results: Inhibition rate = [(number of colonies in control sample - number of colonies in test sample) / number of colonies in control sample] × 100%;

[0135] d. Tensile strength test:

[0136] The standard is based on international standards: ASTM D882 (film tensile properties test) or ISO 527-3, measuring the maximum stress of the film before it breaks;

[0137] d1. Sample preparation:

[0138] Size: Dumbbell-shaped specimen (Type V), gauge length 25mm, width 5mm, total length ≥150mm;

[0139] Direction: Cut 5 specimens along the longitudinal direction (MD) and transverse direction (TD) of the film;

[0140] d2. Test conditions:

[0141] Temperature: 23±2℃, stretching speed: 500mm / min;

[0142] d3. Equipment operation:

[0143] Clamp the specimen in the tensile testing machine fixture and start the test until it breaks;

[0144] Record the maximum tensile force and elongation at break;

[0145] Result calculation: Tensile strength = maximum tensile force (N) / sample cross-sectional area (mm 2 ), unit: MPa; the performance parameters of the composite membranes prepared in Examples 1 to 5 are shown in Table 3:

[0146] Table 3 Performance parameters of composite membranes prepared in Examples 1 to 5

[0147]

[0148] The performance parameters of the composite membranes prepared in Comparative Examples 1 to 5 are shown in Table 4:

[0149] Table 4 Performance parameters of composite membranes prepared in Comparative Examples 1 to 5

[0150]

[0151] 4. Analysis Conclusions:

[0152] Combining the data in Tables 1 to 4, we can see that:

[0153] The oxygen and water vapor permeabilities of the examples were superior to those of the comparative examples, demonstrating that the components within this range can balance the dispersibility of the nanofiller and the density of the polymer matrix. The antibacterial rate of the examples was stable at ≥99.5%, while the antibacterial rate of comparative example 5 dropped sharply to 95.0% due to insufficient silver content. The brittleness of comparative example 3 increased due to excessive boron nitride, resulting in a tensile strength of 55 MPa, but the film material was easily broken. The 48 MPa of example 1 better met the requirements of flexible packaging. Therefore, in the process of preparing the multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film of the present invention, the process parameters and components of examples 1-5 were more advantageous within the range.

[0154] Furthermore, the values of the various materials in Example 1 avoid agglomeration due to excess or functional loss due to deficiency. The plasma treatment power density of 125 watts / square meter precisely activates the surface. The coating solid content of 22.5% achieves uniform coverage. The oxygen permeability is 0.04, the antibacterial rate is 99.9%, and the tensile strength is 48 MPa, all of which meet the core requirements of pharmaceutical packaging for high barrier, strong antibacterial, and mechanical stress resistance. In summary, Example 1 is the best embodiment of the present invention.

[0155] Throughout this specification, references to terms such as "one embodiment," "example," or "specific example" indicate that the specific features, structures, materials, or characteristics described in conjunction with that embodiment or example are included in at least one embodiment or example of the present invention. In this specification, schematic representations of these 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 any one or more embodiments or examples.

[0156] The preferred embodiments of the present invention disclosed above are intended only to help illustrate the present invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the present invention to the specific embodiments described. Obviously, many modifications and variations are possible based on the content of this specification. These embodiments are selected and described in detail in this specification to better explain the principles and practical applications of the present invention, thereby enabling those skilled in the art to better understand and utilize the present invention. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. A method for preparing a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film, characterized in that: It includes a substrate layer, a gas barrier layer, an adhesive transition layer and a nano-ceramic functional coating; The substrate layer comprises the following components by mass: biaxially oriented polypropylene: 80-100 parts; metallocene linear low-density polyethylene: 20-30 parts; nano titanium dioxide: 5-8 parts; β-(3,5-di-tert-butyl-4-hydroxyphenyl)propionic acid: 0.5-1 part; Calcium stearate: 0.3-0.6 parts; The gas barrier layer comprises the following components by mass: 40-60 parts of ethylene-vinyl alcohol copolymer; 15-25 parts of polyvinylidene chloride emulsion; Nano boron nitride flakes: 10-15 parts; modified montmorillonite: 8-12 parts; The bonding transition layer comprises the following components in parts by mass: maleic anhydride grafted polypropylene: 100 parts; Nano silicon carbide whiskers: 3-5 parts; The nano ceramic functional coating comprises the following components in parts by mass: 8-12 parts of nano zinc oxide / silver composite particles; Fumed silica: 5-8 parts; KH-550 silane coupling agent: 2-4 parts; polyhexamethylene biguanide hydrochloride: 1-2 parts; perfluoroalkyl ethyl acrylate copolymer: 3-5 parts; The following preparation steps are also included: S1. The following polymer particles are used for the substrate layer, barrier layer and adhesive layer: Biaxially oriented polypropylene, metallocene linear low-density polyethylene, ethylene-vinyl alcohol copolymer, polyvinylidene chloride emulsion and maleic anhydride grafted polypropylene are placed in a vacuum dryer respectively and dried at 80-100°C for 4-6 hours to reduce the water content to ≤0.02%. At the same time, nano-titanium dioxide, nano-boron nitride flakes, modified montmorillonite, and nano-silicon carbide whisker powder materials are placed in a nitrogen-protected ball mill and dispersed at a speed of 300-400 rpm for 30-60 minutes to ensure uniform particle size distribution; S2. Use three-layer co-extrusion film blowing unit for melt co-extrusion: Substrate layer: 80-100 parts of pretreated biaxially oriented polypropylene, 20-30 parts of metallocene linear low-density polyethylene, 5-8 parts of nano-titanium dioxide, 0.5-1 part of β-(3,5-di-tert-butyl-4-hydroxyphenyl) propionic acid, and 0.3-0.6 parts of calcium stearate are mixed and melt-extruded through a main extruder at 190-210°C; Barrier layer: 40-60 parts of ethylene-vinyl alcohol copolymer, 15-25 parts of polyvinylidene chloride emulsion, 10-15 parts of nano-boron nitride sheet, and 8-12 parts of modified montmorillonite are extruded through a second extruder at 200-230°C; Adhesive layer: Maleic anhydride grafted polypropylene: 100 parts and nano silicon carbide whiskers: 3-5 parts are melted at 180-200°C through a third extruder; After the melt layers are compounded by the distributor, they are extruded from the annular die at a pressure of 0.8-1.2 MPa. The film bubble is cooled and shaped by the air ring. The winding speed is 8-12 m / min, and finally a three-layer composite base film with a total thickness of 80-120 μm is formed. S3. The co-extruded base film is introduced into an atmospheric plasma treatment machine and corona treated in an oxygen / argon mixed gas environment with a treatment power density of 100-150 watts / m2 and a dwell time of 0.5-1.2 seconds to increase the surface tension to 50-55 mN / m and a dyne value ≥40; After treatment, the basement membrane needs to be placed in a constant temperature and humidity chamber for 10-15 minutes to stabilize the surface state; S4. Use a micro-gravure roll coater to evenly coat the nano-ceramic functional coating slurry on the surface of the base film: Mix 8-12 parts of nano zinc oxide / silver composite particles, 5-8 parts of fumed silica, 2-4 parts of KH-550 silane coupling agent, 1-2 parts of polyhexamethylene biguanide hydrochloride, and 3-5 parts of perfluoroalkyl ethyl acrylate copolymer with anhydrous ethanol in a mass ratio of 1:4, and treat with an ultrasonic disperser for 30-40 minutes to form a stable suspension with a solid content of 20-25%; Set the coating roller speed ratio to 1:1.2-1.5 and the base film tension to 8-10N / cm 2 , wet film thickness 10-15μm, after coating, the film material immediately enters the infrared pre-drying zone to make the solvent volatilization rate ≥85%; S5. Place the film in a hot air circulation curing oven and cure it in three stages of gradient temperature increase. After curing, it is quickly cooled to room temperature using a cold roller. The final coating thickness is controlled at 2-3 μm. S6. Finally, use a CNC slitting machine to cut the wide film into the specified width, with a slitting speed of 20-30 meters / minute and a tension control of 5-8N / cm 2 ; The three stages of gradient temperature rise and curing in step S5 are: The first stage: keep warm at 80-100℃ for 2-3 minutes to promote cross-linking of silane coupling agent; The second stage: treatment at 120-140°C for 5-8 minutes to achieve melt leveling of the perfluoroalkyl ethyl acrylate copolymer; The third stage: rapid curing at 160-180℃ for 30-60 seconds to form a dense nano-ceramic coating.

2. The method for preparing a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film according to claim 1, characterized in that: The nano titanium dioxide is prepared by reacting tetrabutyl titanate in an acidic aqueous solution with a pH of 1-3 at 180-220° C. for 6-8 hours through a hydrothermal synthesis method, with a purity of ≥99.5% and a particle size of 20-50 nm.

3. The method for preparing a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film according to claim 2, characterized in that: The nano boron nitride sheet is prepared by mixing boron powder and urea in a molar ratio of 1:3, reacting at 1200-1400°C for 2-4 hours under an ammonia protective atmosphere through a high-temperature vapor deposition method, with a purity of ≥99.9% and a thickness of <10nm.

4. The method for preparing a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film according to claim 1, characterized in that: The modified montmorillonite is prepared by treating natural sodium montmorillonite and hexadecyltrimethylammonium bromide in a mass ratio of 1:0.5 in a 60-80° C. aqueous solution through an ion exchange reaction for 12-24 hours, and the cation exchange capacity is ≥100 mmol / 100 g.

5. The method for preparing a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film according to claim 4, characterized in that: The maleic anhydride grafted polypropylene is prepared by extruding and granulating isotactic polypropylene and maleic anhydride at a mass ratio of 100:5 at 180-200° C. through a melt grafting method under the action of dicumyl peroxide initiator, with a grafting rate of 1.2-1.8%.

6. The method for preparing a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film according to claim 4, characterized in that: The nano zinc oxide / silver composite particles are prepared by dissolving zinc nitrate and silver nitrate in a molar ratio of 10:1, generating a precursor by a coprecipitation method under alkaline conditions of pH = 10-12, and then calcining at 400-500° C. for 2 hours, with a silver loading of 8-12 wt%.

7. The method for preparing a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film according to claim 1, characterized in that: The fumed silica is produced by instantaneously reacting silicon tetrachloride with a hydrogen / oxygen mixed gas in a hydrogen-oxygen flame high-temperature hydrolysis reactor at 1200-1500°C, with a specific surface area of 200-400m 2 / g, purity ≥99.8%.

8. The method for preparing a multi-layer co-extruded nano-ceramic coating high-barrier pharmaceutical packaging composite film according to claim 1, characterized in that: The polyhexamethylene biguanide hydrochloride is prepared by polymerizing guanidine hydrochloride and hexamethylene diamine in a molar ratio of 1:1.2 at 140-160° C. for 4-6 hours under nitrogen protection through a polycondensation reaction, with a polymerization degree n=20-30 and a purity of ≥98%.

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