Preparation process of high-barrier-property composite film for medicine

Abstract

The invention relates to the technical field of medicine packaging materials, and discloses a preparation technology of a high-barrier-property composite film for medicine. Comprising the steps of preparation of a degradable base material, coating of a bio-based pressure-sensitive adhesive, distribution of a gradient inhibitor, interface ion exchange activation, construction of an ion immobilization network, temperature and humidity gradient control curing, formation of a phase interface dehydration protection layer and the like. Through a dual action mechanism of pressure-sensitive adhesion and ion exchange and a synergistic effect of biological activity inhibition and ion migration blocking, efficient compounding of a degradable base material and an inorganic barrier layer is realized, and the technical problems of both environmental protection property and high barrier property, attenuation of interface bonding stability and long-term use performance and the like are solved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical packaging materials technology, and more specifically, to a process for preparing a high-barrier composite film for pharmaceuticals. Background Technology

[0002] With increasingly stringent environmental requirements for pharmaceutical packaging materials, the application of biodegradable materials in the pharmaceutical packaging field has become an industry trend. However, traditional biodegradable materials generally suffer from insufficient barrier properties, making it difficult to meet the stringent requirements of pharmaceuticals for isolation from external factors such as oxygen and water vapor. While traditional high-barrier composite films offer excellent barrier properties, they are typically difficult to degrade, resulting in a severe environmental burden after use. Currently, the composite of biodegradable substrates with inorganic barrier layers is the main technical approach to resolving these contradictions, but the following technical problems in existing technologies urgently need to be addressed: The poor compatibility and weak interfacial bonding between biodegradable substrates and inorganic barrier layers make the composite membrane prone to interlayer separation during use. The interfacial bonding formed by traditional composite processes is unstable under temperature and humidity cycling conditions, affecting the reliability of barrier performance. Bio-based components are prone to degradation during long-term storage, and interfacial ion migration accelerates this process, resulting in a significant decline in the long-term barrier performance of the composite membrane.

[0003] Especially for pharmaceutical packaging distributed globally, maintaining stable barrier properties over long periods under varying climatic conditions is crucial. Therefore, developing a composite membrane preparation process that combines environmental friendliness, high barrier performance, and long-term stability has significant technological value and application prospects. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides a process for preparing a high-barrier composite membrane for pharmaceuticals.

[0005] A process for preparing a high-barrier composite film for pharmaceuticals includes the preparation of a biodegradable substrate, the preparation of an inorganic barrier layer, and a post-processing step for the composite film. The process further includes the following steps: A bio-based pressure-sensitive adhesive containing an enzyme activity inhibitor is coated on a biodegradable substrate, wherein the concentration of the enzyme activity inhibitor increases layer by layer from the biodegradable substrate side to the inorganic barrier layer side, forming a concentration gradient distribution structure. The surface of a biodegradable substrate coated with a bio-based pressure-sensitive adhesive is subjected to low-temperature plasma treatment and then immersed in a multivalent metal salt solution to form exchangeable ions on the surface. A solution of macromolecular chains with multiple coordination groups is sprayed onto the surface of an ion-modified substrate, so that the coordination macromolecular chains form coordination complexes with surface metal ions to construct an ion immobilization network. An inorganic barrier layer and an ion-fixed network layer are laminated and cured under a temperature and humidity gradient, wherein the temperature and humidity gradient is as follows: the temperature on the biodegradable substrate side is 60-70℃ and the relative humidity is 20-30%, and the temperature on the inorganic barrier layer side is 30-40℃ and the relative humidity is 70-80%. A superhydrophobic modified chitosan solution is sprayed onto the surface of the cured composite film. The solvent evaporation rate is controlled to allow the hydrophobic groups to self-assemble into a superhydrophobic micro-region structure. Then, a stable phase interface dehydration protective layer is formed by heat treatment.

[0006] Preferably, the biodegradable substrate is selected from one or more of polylactic acid, polycaprolactone, or polyhydroxyalkanoate.

[0007] Preferably, the bio-based pressure-sensitive adhesive is prepared by mixing rosin ester resin obtained by reacting natural rosin with polyols and vegetable oil, and then adding diisocyanate crosslinking agent to react.

[0008] Preferably, the enzyme activity inhibitor is selected from one or more of curcumin, green tea polyphenols, and rosemary extract.

[0009] Preferably, the concentration gradient of the enzyme activity inhibitor is: 0.5% for the first layer, 1.0% for the second layer, 2.0% for the third layer, and 5.0% for the fourth layer, with each layer having a thickness of 1-2 μm.

[0010] Preferably, the polyvalent metal salt is selected from one or more of calcium chloride, zinc chloride, and magnesium chloride.

[0011] Preferably, the macromolecular chain having multiple coordinating groups is selected from one or more of carboxymethyl cellulose, sodium alginate, and polyacrylic acid.

[0012] Preferably, the material of the inorganic barrier layer is selected from one or more of alumina, silicon oxide, and zinc oxide.

[0013] Preferably, the thickness of the inorganic barrier layer is 10-100 nm.

[0014] Preferably, the superhydrophobic modified chitosan is prepared by hydrophobic modification of chitosan with octadecyl isocyanate, and the water contact angle of the superhydrophobic micro-region structure is not less than 150°.

[0015] Preferably, the heat treatment temperature is 120-130℃ and the time is 5-10 minutes.

[0016] This invention utilizes the dual effects of pressure-sensitive adhesion and ion exchange, combined with the synergistic effects of bioactivity inhibition and ion migration blocking, to prepare a high-barrier composite membrane for pharmaceutical use that is environmentally friendly, has high barrier properties, and long-term stability. The main technical effects are as follows: Environmental performance: This composite film achieves efficient bonding between a biodegradable substrate and an inorganic barrier layer, improving the material's environmental characteristics while maintaining the barrier properties of pharmaceutical packaging. Experimental verification shows that after 90 days under standard composting conditions (58℃, 60% relative humidity), the biodegradable portion of the film achieves a degradation rate of over 90%, while the inorganic barrier layer can be recycled.

[0017] Interfacial bonding strength: Through a sequential composite process of "physical bonding followed by chemical bonding", the interfacial peel strength of the composite film reaches 2.5-3.0 N / cm (tested according to GB / T 2790-1995), which is more than 50% higher than that of conventional composite processes, and the interfacial bonding strength decreases by no more than 10% after repeated bending 200 times.

[0018] Barrier performance: The composite membrane has an oxygen permeability of less than 0.5 cm³ / (m²·day·atm) (tested according to GB / T 1038-2000) and a water vapor permeability of less than 0.5 g / (m²·day) (tested according to GB / T 26253-2010), meeting the packaging requirements for highly sensitive drugs.

[0019] Environmental stability: After experimental testing under simulated different climatic conditions, the barrier performance of the composite film does not decrease by more than 5% under temperature and humidity cycling conditions (-20℃ to 40℃, relative humidity 20% to 80%, 100 cycles), which is better than the more than 30% decrease of traditional processes. It is suitable for pharmaceutical packaging stored and transported under different climatic conditions.

[0020] Long-term stability: Accelerated aging tests verified that the composite membrane prepared using a synergistic technology of bioactivity inhibition and ion migration blocking showed a barrier performance decrease of no more than 10% after 24 months of storage at 25°C and 60% relative humidity, while traditional composite membranes typically exhibited performance degradation of over 40% under the same conditions. Even under extreme conditions (40°C and 80% relative humidity), the composite membrane maintained excellent barrier performance stability, with a barrier performance degradation of no more than 15% within 3 months.

[0021] In summary, this invention successfully solves the technical problems of traditional technologies, such as the difficulty in balancing environmental friendliness and high barrier performance, unstable interfacial bonding, and long-term performance degradation, providing an innovative material solution for the pharmaceutical packaging field that combines environmental friendliness, high barrier performance, and long-term stability. Attached Figure Description

[0022] Figure 1 This is a fluorescence imaging analysis diagram; Figure 2 These are the results of temperature and humidity cycling stability tests; Figure 3 This is a SEM image of the initial interface morphology of sample C. Figure 4 This is a SEM image of the interface morphology of the sample after C72h hydrothermal treatment; Figure 5 This is an EDS line scan analysis - interface element distribution diagram; Figure 6 This is an EDS energy dispersive spectroscopy analysis - interface location diagram; Figure 7 This is a graph showing the depth of water molecule penetration. Figure 8 It is a three-dimensional image of the surface morphology of the superhydrophobic micro-region; Figure 9 This is a top view of the surface morphology of the superhydrophobic micro-region; Figure 10 This is a graph showing the change in barrier performance under accelerated aging conditions. Detailed Implementation

[0023] The subject matter described herein will now be discussed with reference to exemplary embodiments. It should be understood that these embodiments are discussed only to enable those skilled in the art to better understand and implement the subject matter described herein, and changes may be made to the function and arrangement of the elements discussed without departing from the scope of this specification. Various processes or components may be omitted, substituted, or added as needed in the examples. Furthermore, some features described in the examples may be combined in other examples.

[0024] Example 1

[0025] This embodiment proposes a preparation process for a high-barrier composite film for pharmaceuticals, including the preparation of a biodegradable substrate, the preparation of an inorganic barrier layer, and a post-processing step for the composite film. The process further includes the following steps: A bio-based pressure-sensitive adhesive containing an enzyme activity inhibitor is coated on a biodegradable substrate, wherein the concentration of the enzyme activity inhibitor increases layer by layer from the biodegradable substrate side to the inorganic barrier layer side, forming a concentration gradient distribution structure. The biodegradable substrate is selected from polylactic acid; Bio-based pressure-sensitive adhesives are made by mixing rosin ester resin (obtained by reacting natural rosin with polyols) with vegetable oil, and then adding diisocyanate crosslinking agents. Enzyme activity inhibitors are selected from curcumin; The concentration gradient of the enzyme activity inhibitor was as follows: 0.5% for the first layer, 1.0% for the second layer, 2.0% for the third layer, and 5.0% for the fourth layer, with each layer having a thickness of 1.5 μm.

[0026] The surface of a biodegradable substrate coated with a bio-based pressure-sensitive adhesive is subjected to low-temperature plasma treatment and then immersed in a multivalent metal salt solution to form exchangeable ions on the surface. The polyvalent metal salts are selected from calcium chloride.

[0027] A solution of macromolecular chains with multiple coordination groups is sprayed onto the surface of an ion-modified substrate, so that the coordination macromolecular chains form coordination complexes with surface metal ions to construct an ion immobilization network. The macromolecular chain with multiple coordinating groups is selected from carboxymethyl cellulose.

[0028] An inorganic barrier layer and an ion-fixed network layer are laminated and cured under a temperature and humidity gradient, wherein the temperature and humidity gradient is: 65°C and 25% relative humidity on the biodegradable substrate side, and 5°C and 75% relative humidity on the inorganic barrier layer side. The inorganic barrier layer is made of alumina. The thickness of the inorganic barrier layer is 55 nm.

[0029] A superhydrophobic modified chitosan solution is sprayed onto the surface of the cured composite film. The solvent evaporation rate is controlled to allow the hydrophobic groups to self-assemble and form a superhydrophobic micro-region structure. Then, a stable phase interface dehydration protective layer is formed by heat treatment. Superhydrophobic modified chitosan is prepared by hydrophobic modification of chitosan with octadecyl isocyanate, and the water contact angle of the superhydrophobic micro-region structure is not less than 150°. The heat treatment temperature was 125℃ and the time was 8 minutes.

[0030] Example 2

[0031] The difference between this embodiment and Embodiment 1 is that: The biodegradable substrate is selected from polycaprolactone; Enzyme activity inhibitors are selected from green tea polyphenols; The concentration gradient of the enzyme activity inhibitor was as follows: 0.5% for the first layer, 1.0% for the second layer, 2.0% for the third layer, and 5.0% for the fourth layer, with each layer having a thickness of 1 μm.

[0032] The polyvalent metal salt is selected from zinc chloride.

[0033] The macromolecular chain with multiple coordinating groups is selected from sodium alginate.

[0034] An inorganic barrier layer and an ion-fixed network layer are laminated and cured under a temperature and humidity gradient, wherein the temperature and humidity gradient is: 60°C and 20% relative humidity on the biodegradable substrate side, and 30°C and 70% relative humidity on the inorganic barrier layer side. The inorganic barrier layer is made of silicon dioxide. The thickness of the inorganic barrier layer is 10 nm.

[0035] The heat treatment temperature is 120℃ and the time is 5 minutes.

[0036] Example 3

[0037] The difference between this embodiment and Embodiment 1 is that: The biodegradable substrate is selected from polycaprolactone and polyhydroxyalkanoates; Enzyme activity inhibitors were selected from green tea polyphenols and rosemary extract; The concentration gradient of the enzyme activity inhibitor was as follows: 0.5% for the first layer, 1.0% for the second layer, 2.0% for the third layer, and 5.0% for the fourth layer, with each layer having a thickness of 2 μm.

[0038] The polyvalent metal salts are selected from zinc chloride and magnesium chloride.

[0039] The macromolecular chain with multiple coordinating groups is selected from sodium alginate and polyacrylic acid.

[0040] An inorganic barrier layer and an ion-fixed network layer are laminated and cured under a temperature and humidity gradient, wherein the temperature and humidity gradient is: 70°C and 30% relative humidity on the biodegradable substrate side, and 40°C and 80% relative humidity on the inorganic barrier layer side. The inorganic barrier layer is made of silicon dioxide and zinc oxide. The thickness of the inorganic barrier layer is 100 nm.

[0041] The heat treatment temperature was 130℃ and the time was 10 minutes.

[0042] Example 4

[0043] This embodiment presents a process for preparing a high-barrier composite membrane for pharmaceuticals, which mainly includes the following specific implementation steps: 1. Preparation of biodegradable substrates Biodegradable polymer materials such as polylactic acid (PLA, molecular weight range 80,000-200,000 Daltons, melting point 155-170℃), polycaprolactone (PCL, molecular weight range 40,000-80,000 Daltons, melting point 58-65℃), or polyhydroxyalkanoate (PHA, molecular weight range 50,000-100,000 Daltons, melting point 160-175℃) are selected and substrate films with a thickness of 20-100μm are prepared by extrusion, casting, or blow molding processes.

[0044] The process parameters are controlled as follows: Extrusion temperature: PLA 180-220℃, PCL 90-120℃, PHA 170-200℃; Extrusion rate: 15-30 kg / h; Traction speed: 5-15 m / min; Cooling temperature: 15-25℃.

[0045] During the substrate preparation process, additives such as citrate ester plasticizers (3-8% of the substrate mass) and ethylene-vinyl acetate (EVA) toughening agents (5-10% of the substrate mass) can be added to adjust the mechanical properties of the substrate. The prepared substrate film should have the following performance indicators: tensile strength ≥30 MPa (determined according to GB / T 1040.1-2006), elongation at break ≥200% (determined according to GB / T 1040.1-2006), and haze ≤3% (determined according to GB / T 2410-2008).

[0046] 2. Preparation and Coating of Bio-based Pressure-sensitive Adhesives 2.1 Preparation of Bio-based Pressure-sensitive Adhesive Pressure-sensitive bio-based adhesives are prepared using renewable resources such as natural rosin (acid value 165-185 mg KOH / g, softening point 70-80℃, camphor rosin or Qishan rosin), castor oil (iodine value 82-90, viscosity 950-1050 mPa·s, acid value ≤2.0 mg KOH / g), or citrus essential oil (d-limonene content ≥95%) as main raw materials through esterification, polymerization, and other reactions. The specific steps are as follows: 1) Mix rosin and polyol (pentaerythritol, purity ≥98%, melting point 250-260℃) in a 500-1000ml four-necked flask at a molar ratio of 3:1, and add p-toluenesulfonic acid at a mass fraction of 0.05-0.1% as a catalyst; 2) Under nitrogen protection, use mechanical stirring (200-300 rpm) and heat to 150-180℃ for 4-6 hours for esterification reaction. During the process, measure the acid value every 30 minutes. When the acid value drops to 25-35 mg KOH / g, the reaction is complete and rosin ester resin is obtained. 3) Mix rosin ester resin and vegetable oil (castor oil) in a stainless steel reactor at a mass ratio of 2:1, add 2-3% diisocyanate crosslinking agent (toluene diisocyanate or hexamethylene diisocyanate), and react at 80-100℃ for 2-3 hours using a paddle stirrer (150-200 rpm). Take samples every 30 minutes to test the viscosity. When the viscosity reaches 3000-5000 mPa·s (25℃, measured by a Brookfield viscometer), a pressure-sensitive adhesive bio-based adhesive is obtained. 4) Add 1-5% of cyclic monoterpenoids (such as limonene, purity ≥95%) to the bio-based adhesive, stir at 60-70℃ for 30-60 minutes, adjust its viscosity to 2000-3000 mPa·s (25℃), and its flowability index to 0.8-1.2 (as determined by ASTM D1238) to make it suitable for coating processes.

[0047] The prepared bio-based pressure-sensitive adhesive should have the following characteristics: viscosity: 2000-3000 mPa·s (25℃, determined according to GB / T 10247-2008); initial tack: ≥8 N / 25mm (determined according to FINAT FTM9); holding power: ≥24 hours (determined according to FINAT FTM8); bio-based carbon content: ≥50% (determined according to ASTM D6866).

[0048] 2.2 Gradient distribution of enzyme activity inhibitors A multi-layer continuous coating process was used to combine the enzyme activity inhibitor with the bio-based pressure-sensitive adhesive prepared in Section 2.1, forming a concentration gradient distribution in the adhesive layer. The specific steps are as follows: 1) Select natural inhibitors that selectively inhibit microbial enzymes without affecting the biodegradability of materials: curcumin (purity ≥95%, antioxidant activity ≥80%, soluble in ethanol); green tea polyphenols (EGCG content ≥40%, total polyphenol content ≥90%, water-soluble); rosemary extract (total content of rosmarinic acid and carrageenan acid ≥20%, soluble in vegetable oil). Rosemary extract is preferred because it has the best compatibility with bio-based pressure-sensitive adhesives. 2) Divide the bio-based pressure-sensitive adhesive prepared in Section 4.2.1 into four equal parts. Add different concentrations of inhibitor to each part using a high-shear mixer (1000-1500 rpm) at 65-75℃: Part 1: 0.5% (by weight of adhesive), mix for 15-20 minutes until homogeneous; Part 2: 1.0% (by weight of adhesive), mix for 15-20 minutes until homogeneous; Part 3: 2.0% (by weight of adhesive), mix for 15-20 minutes until homogeneous; Part 4: 5.0% (by weight of adhesive), mix for 15-20 minutes until homogeneous. The criteria for judging homogeneity are: no obvious particles or agglomerates are observed under a microscope (100x), and the absorbance difference between different parts of the sample, as detected by a UV spectrophotometer, does not exceed 5%. 3) A four-layer synchronous precision coating machine (accuracy ±0.1μm) is used to sequentially coat adhesive layers containing different concentrations of inhibitors onto the biodegradable substrate. The coating temperature is controlled at 55-65℃, the coating speed is 5-8 m / min, and the coating pressure is 0.2-0.3 MPa. 4) Coating process: First, coat an adhesive layer containing 0.5% inhibitor with a thickness of 1-2 μm on the biodegradable substrate. Then, coat an adhesive layer containing 1.0% inhibitor with a thickness of 1-2 μm. Next, coat adhesive layers containing 2.0% and 5.0% inhibitor in sequence, each with a thickness of 1-2 μm. The time interval between each layer should be controlled at 10-15 seconds to ensure good fusion but not complete mixing between the layers. Finally, a gradient adhesive layer with a total thickness of 4-8 μm is formed.

[0049] 5) Precisely controlled drying process after coating: Use a three-stage hot air drying tunnel with a temperature gradient of 40℃→55℃→45℃; drying time is 1.5-2.5 minutes, controlling solvent evaporation to 60-70% (monitored in real time by an infrared thickness gauge); maintain appropriate fluidity, with a fluidity index between 1.0 and 1.5 (measured according to ASTM D1238); the viscosity of the dried coating should be 4000-6000 mPa·s (25℃, measured according to GB / T 10247-2008).

[0050] The prepared gradient-distribution adhesive layer should have the following characteristics: interlayer bonding strength: ≥1.5 N / cm (determined according to GB / T 2792-2014); inhibitor concentration gradient: confirmed by high performance liquid chromatography (HPLC) that the inhibitor concentration from the bottom layer to the surface layer is distributed in a gradient of 0.5%→1.0%→2.0%→5.0%, with the concentration error of each layer not exceeding ±10%; enzyme activity inhibition rate: under the conditions of 25℃ and 60% relative humidity, the inhibition rate of microbial lipase in the bottom layer is 30-40%, and that in the surface layer is 90-95% (determined according to GB / T 24253-2009).

[0051] This process creates a gradient distribution structure of inhibitor concentration from low to high: low concentration on the biodegradable substrate side maintains the biodegradability of the substrate (degradation rate ≥85%), while high concentration on the inorganic barrier layer side provides interfacial biostability (enzyme activity inhibition rate ≥90%), thus solving the problem of balancing environmental protection and long-term stability.

[0052] 3. Interface ion exchange activation process 3.1 Ion modification of biodegradable substrate surface The surface of a biodegradable substrate coated with a gradient adhesive layer is subjected to ion modification treatment to introduce exchangeable ions, preparing it for subsequent ion exchange reactions. 1) Low-temperature plasma treatment technology is adopted (equipment parameters: power density 40-60 W / cm², frequency 13.56MHz). The treatment conditions are: working gas: oxygen and argon mixture (volume ratio 1:4); gas pressure: 30-50 Pa; treatment time: 20-40 seconds; substrate temperature: not exceeding 40℃ (water-cooled temperature control). Through this treatment, active functional groups such as carboxyl and hydroxyl groups are generated on the surface of the adhesive layer. The functional group density should reach 3.5-4.5 μmol / cm² (measured by XPS). 2) Immerse the activated substrate in a polyvalent metal salt aqueous solution using an impregnation device (speed controlled at 2-3 m / min): Metal salt selection: calcium chloride (CaCl2·2H2O, analytical grade ≥99%), zinc chloride (ZnCl2, analytical grade ≥98%), or magnesium chloride (MgCl2·6H2O, analytical grade ≥99%); Solution concentration: 0.5-2.0% (w / v); Solution pH: 5.0-6.0 (adjusted with citric acid); Impregnation temperature: 20-25℃; Impregnation time: 1-3 minutes. This process allows the surface-active functional groups to combine with metal ions, and the metal ion loading should reach 1.0-1.5 mg / cm² (determined by atomic absorption spectrometry). 3) Rinse the surface with deionized water (conductivity <0.5 μS / cm) at a pressure of 0.2-0.3 MPa for 10-15 seconds to remove unbonded metal salts; then dry the material with a hot air drying device (temperature 40-50℃, wind speed 10-15 m / s) for 30-60 seconds to reduce the moisture content to less than 1% (measured by a Karl Fischer moisture analyzer).

[0053] The surface modified with metal ions should have the following characteristics: contact angle: 35-45° (measured according to GB / T 30693-2014); surface energy: 58-65 mJ / m² (measured according to ASTM D7490); ion exchange capacity: 2.5-3.5 meq / g (measured according to GB / T7324-2000).

[0054] 3.2 Ion Immobilization Network Construction Process By introducing macromolecular chains that can form stable coordination structures with mobile ions, active ions are fixed at the target positions: 1) Select macromolecular chains with multiple coordinating groups: carboxymethyl cellulose (CMC, degree of substitution 0.7-0.9, viscosity 300-500 mPa·s, 1% aqueous solution); sodium alginate (viscosity 150-250 mPa·s, 1% aqueous solution, M / G ratio 1.5-1.8); polyacrylic acid (PAA, molecular weight 50,000-70,000, degree of crosslinking <1%). Carboxymethyl cellulose is preferred because it has the best coordination ability and stability. 2) Prepare an aqueous solution of the selected macromolecular chain: concentration: 0.1-0.5% (w / v); dissolution method: stir in deionized water at 60-70℃ using a variable frequency stirrer (300-400 rpm) for 1-2 hours until completely dissolved; adjust the pH value to 5.5-6.5 using a citric acid / sodium bicarbonate buffer system; filter (5 μm filter membrane) to remove insoluble matter.

[0055] 3) Add crosslinking agent to the solution: Crosslinking agent type: glutaraldehyde (purity ≥25%, aqueous solution) or diglycidyl dimethylmalonate (purity ≥98%); Amount added: 0.05-0.2% (relative to the mass of the macromolecular chain); Addition method: Add slowly dropwise after dilution, stirring speed 450-500 rpm; Reaction conditions: Stir at room temperature (20-25℃) for 30-60 minutes. This process allows a suitable crosslinking network to form between the macromolecular chains, and the solution viscosity should increase by 30-50% (monitored by rotational viscometer). 4) A precision micro-spraying process is used to uniformly spray the coordination macromolecular chain solution onto the surface of the ion-modified substrate: Spraying equipment: ultrasonic atomizing nozzle (frequency 80-120 kHz); spraying distance: 10-15 cm; spraying pressure: 0.15-0.25 MPa; spraying speed: 0.5-1.0 ml / cm² / min; substrate temperature: 35-40℃. A coordination layer with a wet film thickness of 5-10 μm is formed, and the thickness uniformity is controlled within ±5% (monitored in real time by a laser thickness gauge). 5) Control the drying parameters for precise curing: Temperature: 45-55℃; Relative humidity: 40-60% (controlled by steam injection); Curing time: 3-5 minutes; Curing condition monitoring: Real-time monitoring of the formation of carboxyl group and metal ion coordination peaks by Fourier transform infrared spectroscopy (FTIR). Through this process, the coordination macromolecular chain and the surface metal ions form coordination complexes to construct an ion fixation network.

[0056] The ion immobilization network layer should have the following characteristics: thickness: 2-4 μm (dry film, determined by microsection and optical measurement); degree of crosslinking: 25-35% (determined by swelling experiment); binding rate of coordinating metal ions: ≥85% (determined by ICP-AES); ion immobilization stability: after immersion in water at 80℃ for 24 hours, the ion release rate is <5% (determined by atomic absorption spectrometry).

[0057] This process creates an ion-fixed network structure: surface metal ions are fixed in stable positions by the coordination groups of macromolecular chains, while retaining 15-20% ion exchange activity. It can form a stable ion exchange balance with the inorganic barrier layer and resist ion migration under humid and hot conditions (ion migration rate <3% after 72 hours at 80℃ and 85% relative humidity), thus solving the long-term stability problem of the interface bonding network of traditional composite membranes.

[0058] 4. Preparation and composite of inorganic barrier layers 4.1 Preparation of Inorganic Barrier Layer Inorganic barrier layers were prepared using physical vapor deposition (PVD) or chemical vapor deposition (CVD) methods: 1) Select inorganic barrier materials: Alumina (Al2O3, purity ≥99.99%): excellent water vapor barrier performance; Silicon oxide (SiO2, purity ≥99.99%): excellent transparency and stability; Zinc oxide (ZnO, purity ≥99.99%): has certain antibacterial properties. Alumina is preferred because it has the best overall barrier performance. 2) Use one of the following deposition processes: magnetron sputtering: target material: high-purity alumina (or metallic aluminum + reactive oxygen); power density: 2-4 W / cm²; working pressure: 0.2-0.5 Pa; substrate temperature: not exceeding 60℃; sputtering time: adjusted according to thickness requirements, generally 5-15 minutes.

[0059] Electron beam evaporation: Evaporation source material: high-purity alumina (or metallic aluminum + oxygen atmosphere); Electron beam power: 3-5 kW; Working air pressure: 0.01-0.05 Pa; Evaporation rate: 0.2-0.5 nm / s; Substrate temperature: not exceeding 50℃; Plasma-enhanced chemical vapor deposition (PECVD): Precursor: Trimethylaluminum (TMA) + Oxygen / Ozone; Plasma power: 100-300 W; Frequency: 13.56 MHz; Working air pressure: 10-30 Pa Base temperature: not exceeding 80℃.

[0060] 3) Deposition on a temporary storage carrier: Temporary storage carrier: polyethylene terephthalate (PET) film, 12-25 μm thick, surface tension 38-42 mN / m; Temporary storage carrier pretreatment: low-intensity corona treatment (power 100-150 W) to increase surface energy to 46-50 mN / m; Deposition thickness control: 10-100 nm, thickness uniformity requirement ±5% (real-time monitoring via quartz crystal microbalance); Deposition rate control: 0.2-0.5 nm / s; Substrate temperature control: not exceeding 60℃ (temperature controlled by water cooling system).

[0061] 4) Precise control of the deposition process to form a dense and uniform barrier structure: oxygen partial pressure control (for reactive deposition) 0.05-0.1 Pa; substrate rotation speed: 5-10 rpm (to ensure uniformity); deposition interval cooling: 1-2 minutes of cooling after every 30 nm deposition; online thickness monitoring: using an ellipsometer or optical thickness monitor.

[0062] 5) Post-deposition processing: Preparation of roll A: Use a cooling stripping roller system (temperature 10-15℃, linear speed 1-2m / min) to peel the inorganic barrier layer from the temporary carrier; Preparation of roll B: Directly use the temporary carrier side to perform subsequent lamination with the biodegradable substrate treated with ion fixation network.

[0063] The inorganic barrier layer should possess the following performance characteristics: Thickness: preferably 30-60 nm (verified by cross-sectional measurement using scanning electron microscopy); Transparency: visible light transmittance ≥90% (determined according to GB / T 2410-2008); Density: ≥95% (evaluated by cross-sectional SEM observation); Crystallinity: amorphous or nanocrystalline structure (confirmed by X-ray diffraction analysis); Surface roughness: Ra value ≤2 nm (determined by atomic force microscopy); Refractive index: Al2O3 1.62-1.65, SiO2 1.45-1.47 (determined by ellipsometer). 4.2 Temperature and Humidity Gradient Controlled Curing Process Utilizing temperature and humidity gradients to promote the directional migration of active groups in pressure-sensitive adhesives and enhance interfacial bonding: 1) The prepared ion-fixed network layer and inorganic barrier layer are laminated using a precision laminating machine: Lamination method: four-roll lamination system (two sets of hard rubber rollers + steel rollers); Pressure control: 5-10 N / cm² (monitored in real time by pressure sensor); Roller temperature control: 50-55℃; Linear speed: 2-3 m / min; Tension control: 50-60 N / m on the biodegradable substrate side, 30-40 N / m on the inorganic barrier layer side. Through this step, the two layers are initially in full contact, with a contact area of ​​over 98% (detected by optical microscope). 2) The composite system is transported to a specially designed temperature and humidity gradient control chamber: Chamber structure: Dual-zone independent temperature and humidity control, temperature control accuracy ±1℃, humidity control accuracy ±3%RH - Chamber parameter settings: Biodegradable substrate side: temperature 60-70℃, relative humidity 20-30% (controlled by hot air circulation and desiccant); Inorganic barrier layer side: temperature 30-40℃, relative humidity 70-80% (controlled by condensation temperature control and atomized water); Gradient monitoring: a temperature and humidity sensor is set every 10 cm to ensure uniform gradient; Transport speed: 0.5-1.0 m / min; 3) Maintain under gradient conditions for 30-60 minutes (adjust according to substrate thickness). During this process, the following changes occur: hydrophilic groups (carboxyl groups, hydroxyl groups, etc.) in the pressure-sensitive adhesive migrate directionally along the temperature and humidity gradient (from high temperature and low humidity to low temperature and high humidity); the migration process is monitored by fluorescently labeled molecules, and the migration distance should reach 0.5-1.5 μm; hydrophilic groups are enriched at the interface of the inorganic barrier layer, with the concentration increasing by 50-80% (analyzed by ATR-FTIR); a network of hydrogen bonds and ionic bonds is formed at the interface, and the binding strength gradually increases; 4) After the gradient treatment is completed, the entire system is transported to the curing zone: Heating method: infrared heating, heating rate 2-3℃ / min; final temperature: 80-90℃; holding time: 10-20 minutes; cooling method: natural cooling to room temperature, cooling rate controlled at 1-2℃ / min to complete the final curing. During this process, the interfacial chemical bonds are further formed and stabilized.

[0064] By controlling the curing process through temperature and humidity gradients, the directional migration and alignment of active groups in pressure-sensitive adhesives were achieved, resulting in an interfacial bonding strength of 2.0-2.5 N / cm (measured according to GB / T 2790-1995), which is 40-60% higher than that of conventional isothermal curing. The key feature of this process is that it utilizes the surface energy difference generated by the temperature and humidity gradient to drive the directional alignment of molecules, forming a more stable interfacial structure. Under cyclic temperature and humidity conditions, the interfacial bonding strength decreases by no more than 10%.

[0065] 5. Process for forming the dehydration protective layer at the phase interface By forming superhydrophobic interface microdomains, water molecule-mediated ion migration and biodegradation are blocked: 1) Preparation of hydrophobically modified chitosan solution: Basic parameters of chitosan: molecular weight 80,000-120,000 Da, degree of deacetylation 85-95%, viscosity 200-400 mPa·s (1% solution); Hydrophobic modification method: grafting reaction using octadecyl isocyanate, grafting rate controlled at 15-25% (determined by NMR); Solvent system: acetic acid / water mixed solution (V:V=1:20), pH 4.5-5.0; Solution concentration: 0.2-0.5% (w / v); Dissolution conditions: stirring at room temperature (20-25℃) for 6-12 hours, homogenizing using a high shear disperser (10,000-15,000 rpm) for 5 minutes; Filtration: removing insoluble matter using a 5 μm pore size filter. 2) Addition and preparation of superhydrophobic modifier: Selection of superhydrophobic modifier: perfluorooctyltrichlorosilane (FOTS, purity ≥97%) or perfluorodecyltriethoxysilane (FDTS, purity ≥95%); Addition amount: 0.05-0.1% (relative to solution mass); Addition method: first dissolve the modifier in a small amount of anhydrous ethanol (1:10 ratio), and slowly add it dropwise to the chitosan solution; Mixing conditions: mix at 30-35℃ using magnetic stirring (400-500 rpm) for 30-60 minutes; Ultrasonic treatment: frequency 40kHz, power 100-150 W, treatment for 5-10 minutes to ensure complete dispersion of the modifier. The prepared solution should have a low surface tension (≤25 mN / m, determined according to ASTM D1331).

[0066] 3) Employing a microphase separation process to control the solvent evaporation rate and form a specific microphase separation structure: Using a precision micro-spray system (nozzle diameter 50-100 μm, working pressure 0.15-0.25 MPa) to uniformly spray the solution onto the surface of the composite film that has undergone temperature and humidity gradient curing: Spraying amount: 0.5-1.0 g / m²; Spraying distance: 15-20 cm; Spraying speed: 5-10 m² / min; Spraying pattern: cross grid pattern to ensure uniform coverage.

[0067] Precisely controlled drying conditions are employed. Temperature: 35-45℃ (controlled by an infrared heating system); Relative humidity: 20-30% (controlled by a dry air system); Airflow velocity: 0.5-1.0 m / s (laminar flow); Drying time: 3-5 minutes; During controlled solvent evaporation, hydrophobic and hydrophilic groups spontaneously separate, forming a nanoscale phase-separated structure: Perfluoroalkyl chains form hydrophobic microregions (50-200 nm in diameter) with long-chain alkyl side groups. Chitosan backbone forms hydrophilic microdomains (10-30 nm wide). Forming micro- and nano-structures similar to the "lotus leaf effect" (verified by atomic force microscopy). Surface morphology parameters: roughness (Ra) is 30-50 nm, and surface fractal dimension is 2.5-2.8.

[0068] 4) Heat treatment and structural stabilization: Heat treatment equipment: precision hot air circulating oven or infrared tunnel furnace; heat treatment temperature: 120-130℃ (monitored in real time by thermocouple array); heat treatment time: 5-10 minutes; heat treatment atmosphere: dry nitrogen (relative humidity <5%); cooling conditions: slow cooling to room temperature (cooling rate 2-3℃ / min). This process fixes the microphase separation structure through cross-linking reaction, forming a stable superhydrophobic interface structure.

[0069] The completed dehydration protective layer at the phase interface should have the following characteristics: Thickness: 0.3-0.5 μm (measured by confocal microscopy); Water contact angle: ≥150° (measured according to GB / T 30693-2014); Roll-off angle: ≤5° (measured according to ASTM D7334); Surface energy: ≤15 mJ / m² (measured according to ASTM D7490); Water vapor permeability rate: ≤0.1 g / (m²·24h) (measured according to ASTM F1249); Durability: Tape peel test (ASTM D3359) peel rate <5%; Chemical resistance: Contact angle change <5% after immersion in pH 3-11 for 24 hours.

[0070] This process forms a superhydrophobic protective layer with a special microstructure in the interface region. These hydrophobic microregions can maintain a local low humidity environment (local relative humidity <30%, measured by a micro humidity sensor) even in environments with a relative humidity as high as 95%, effectively blocking water molecules from penetrating to the interface (water resistance >95%, measured by a tracer method), preventing water molecule-mediated ion migration (ion mobility <2%) and biodegradation processes (enzyme activity reduction >90%), and protecting the long-term stability of the composite membrane.

[0071] 6. Post-processing of composite membranes 1) The prepared composite film is laminated with other functional layers (such as printing layers, protective layers, etc.) using a roll-to-roll lamination process; 2) Perform subsequent processing on the composite film, such as cutting and punching; 3) Conduct quality testing on the product, including testing of indicators such as barrier properties, mechanical properties, and interfacial bonding strength.

[0072] Experiments have shown To verify the technical effects of the present invention, the following experiments were conducted: Experiment 1: Test of the effect of gradient distribution of enzyme activity inhibitors.

[0073] Experimental Objective The gradient distribution structure of enzyme activity inhibitors was verified to simultaneously achieve biodegradability on the biodegradable substrate side and biostability on the inorganic barrier layer side.

[0074] Experimental materials The gradient distribution enzyme activity inhibitor composite membrane (sample A) prepared according to embodiment 1. A composite membrane with 0.5% enzyme activity inhibitor evenly distributed (control sample B1). A composite membrane with 5.0% enzyme activity inhibitor evenly distributed (control sample B2). Composite membrane without enzyme activity inhibitors (control sample B3); Lipase solution (5 U / ml, pH 7.0 phosphate buffer). Standard composting medium (prepared according to ISO 14855-1:2012); Experimental steps Each sample was cut into 5cm×5cm pieces, with 5 parallel samples per group.

[0075] Enzyme activity inhibition test: The sample was placed in a lipase solution and incubated at a constant temperature of 37°C. Samples were taken at 0h, 24h, 48h, and 72h to determine enzyme activity (according to GB / T 24253-2009 method).

[0076] Local degradation test: The samples were buried in standard composting medium at 58°C and 60% relative humidity. Samples were taken at 30, 60, and 90 days to determine the degradation rate of each layer.

[0077] Fluorescent labeling imaging: The distribution of lipase in the composite membrane was observed using FITC-labeled lipase. The degradation products were labeled with Rhodamine B, and the degradation process was observed.

[0078] Experimental results Table 1-1 Enzyme activity inhibition rate (%) of different samples in enzyme solution

[0079] Table 1-2 Degradation rate (%) of different samples under composting conditions

[0080] Figure 1 A fluorescence imaging analysis diagram is shown.

[0081] Experimental conclusions Experimental results showed that the composite film with gradient-distributed enzyme activity inhibitors (sample A) maintained good biodegradability on the degradable substrate side (degradation rate reached 89.2% after 90 days) while exhibiting excellent biostability on the inorganic barrier layer side (enzyme activity inhibition rate reached 92.3%). Fluorescence imaging analysis further confirmed the gradient distribution characteristics of the inhibitors. Compared with the control sample with uniformly distributed inhibitors, the gradient distribution structure successfully achieved a balance between biodegradability and biostability.

[0082] Experiment 2: Damp-heat stability test of ion fixation network.

[0083] Experimental Objective The stability of the ion immobilization network structure under humid and hot conditions was verified, demonstrating that it can effectively prevent ion migration and maintain interfacial bonding strength.

[0084] Experimental materials An ion-fixed network composite membrane (sample C) prepared according to Embodiment 1. Traditional ion-exchange composite membrane (control sample D1). Conventional hot-pressed composite film (control sample D2); Constant temperature and humidity chamber; Inductively coupled plasma atomic emission spectrometer (ICP-AES); Interface peel strength tester (configured according to GB / T 2790-1995); Transparent sink; A device for simulating temperature and humidity circulation during cross-border transportation.

[0085] Experimental steps Each sample was cut into 10cm×10cm pieces, with 5 parallel samples per group; Ion migration test in humid and hot environment: Place the sample in a constant temperature and humidity chamber (80℃, relative humidity 85%). Samples were taken at 0h, 24h, 48h, and 72h respectively; ICP-AES was used to analyze changes in metal ion content in the interface region. Calculate ion mobility; Interface bonding strength test: The peel strength before and after wet heat treatment was determined using an interfacial peel strength tester. Calculate the strength retention rate; Temperature and humidity cycling stability test: The sample was placed in a device simulating cross-border transportation temperature and humidity circulation. Cyclic conditions: -20℃ to 40℃, relative humidity 20% to 80%; Cycle duration: 4 hours, total number of cycles: 100; The interfacial bonding strength was measured after every 10 cycles. Experimental results Table 2-1 Ion mobility (%) of different samples under humid and hot conditions

[0086] Table 2-2 Retention rate of interfacial bond strength after damp heat treatment (%)

[0087] Table 2-3 Changes in interfacial bonding strength of different samples over time at 80℃ / 85%RH (N / cm)

[0088] Figure 2 The results of temperature and humidity cycling stability tests are presented.

[0089] Figure 3 The results of scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) are presented.

[0090] Experimental conclusions Experimental results show that the ion-fixed network structure (sample C) exhibits excellent stability under humid and hot conditions: the ion mobility after 72 hours is only 2.8%, far lower than the 35.2% of the traditional ion-exchange composite membrane (control sample D1). SEM and EDS analyses further confirm that the ion-fixed network effectively anchors metal ions at specific locations, preventing ion migration under humid and hot conditions. Interfacial bonding strength tests show that the ion-fixed network structure retains 91.0% of its strength after humid and hot treatment, while the traditional ion-exchange and thermo-pressed composite membranes only retain 61.4% and 52.2%, respectively. Temperature and humidity cycling tests further confirm the long-term stability of the ion-fixed network; after 100 cycles, the strength retention rate is still as high as 94.2%, while the control samples D1 and D2 decreased to 56.8% and 43.5%, respectively. This significant advantage in humid and hot stability stems from a unique ion-fixed network construction process, which uses macromolecular chain coordinating groups to anchor metal ions at stable positions while retaining some ion exchange activity, achieving a significant improvement in interfacial bonding strength and environmental stability.

[0091] Experiment 3: Test on the water-blocking effect of superhydrophobic interface micro-regions.

[0092] Experimental Objective The study verified the barrier effect of the superhydrophobic interface micro-region structure on water molecules, demonstrating that it can effectively block water molecules from penetrating to the interface, prevent water molecule-mediated ion migration and biodegradation processes, and thus protect the long-term stability of the composite membrane.

[0093] Experimental materials The composite membrane containing superhydrophobic interface microregions prepared according to Embodiment 1 (sample E). Composite membrane without superhydrophobic protective layer (control sample F1); Conventional hydrophobic coating composite membrane (control sample F2); Water contact angle tester (configured according to GB / T 30693-2014); Water vapor transmission rate tester (configured according to GB / T 26253-2010); Miniature humidity sensor (0.5mm diameter, accuracy ±2%RH); High humidity environment simulation chamber (relative humidity can be controlled at 95±1%). Transparent water sample permeability testing device; Fluorescent tracer (FITC-labeled water molecule tracer); Confocal laser scanning microscope (CLSM).

[0094] Experimental steps Cut each sample to an appropriate size, with 5 parallel samples per group; Water contact angle and roll-off angle test: The static water contact angle of each sample surface was determined using a water contact angle tester. Measure the roll angle of each sample surface; Characterization of superhydrophobic micro-region structure: The surface microstructure was observed using atomic force microscopy (AFM); Calculate surface roughness parameters; Local humidity environment test: Place miniature humidity sensors on the surfaces of different samples; The sample was placed in a high humidity environment simulation chamber (relative humidity 95%). Record real-time humidity changes around the sensor.

[0095] Water molecule permeation test: Use fluorescent tracers to label water molecules; Exposing samples to high humidity environments; The penetration depth and distribution of water molecules in the sample were observed using CLSM.

[0096] Long-term barrier stability test: The water vapor transmission rate of each sample was measured under different humidity conditions. Changes in interfacial bonding strength and barrier properties after long-term exposure (0, 30, 60, 90 days) in a high-humidity environment were tested.

[0097] Experimental results Table 3-1 Surface hydrophobicity of different samples

[0098] Table 3-2 Results of localized humidity test at the interface under high humidity conditions (%RH)

[0099] Table 3-3 Changes in water vapor transmission rate of different samples in high humidity environment (g / (m²·day))

[0100] Table 3-4 Results of water droplet rolling test on different samples

[0101] Figure 7 A graph showing the depth of water molecule penetration is displayed.

[0102] Figure 8 A three-dimensional image of the surface morphology of the superhydrophobic micro-region is shown.

[0103] Figure 9 A top view of the surface morphology of the superhydrophobic micro-region is shown.

[0104] Figure 10 The graph shows the changes in barrier performance under accelerated aging conditions.

[0105] Experimental conclusions Experimental results show that the superhydrophobic interface microstructure (sample E) exhibits excellent water-blocking performance: the water contact angle is as high as 153.5°, meeting the requirement of ≥150° in the implementation method, which is much higher than that of conventional hydrophobic coatings (112.6°) and samples without protective layers (72.3°); the roll-off angle is only 3.2°, meeting the characteristic of ≤5° in the implementation method, demonstrating excellent self-cleaning effect. Microscopic morphology analysis confirms that its surface has multi-scale structural features, with a roughness in the range of 30-50 nm, forming a typical Cassie-state superhydrophobic surface.

[0106] High humidity environment testing showed that even under conditions of 95% relative humidity, the superhydrophobic interface microregion could still maintain the local humidity at a low level of 27.5% (consistent with the "local relative humidity <30%" described in the implementation method), while the local humidity of the interface of the unprotected and conventional hydrophobic coating samples reached 92.3% and 65.7%, respectively. Water molecule penetration experiments further demonstrated that after 72 hours of exposure to high humidity, the water molecule penetration depth of the superhydrophobic interface microregion was only 0.6 μm, while the unprotected and conventional hydrophobic coating samples reached 28.7 μm and 13.5 μm, respectively.

[0107] Long-term barrier performance testing showed that the water vapor permeability of the superhydrophobic interface micro-structure increased from the initial 0.38 g / (m²·day) to 0.46 g / (m²·day) after 90 days in a high-humidity environment, an increase of only 21%, consistently remaining below the 0.5 g / (m²·day) specified in the implementation method. In contrast, the unprotected and conventional hydrophobic coating samples increased by 345% and 163% respectively, significantly exceeding the standard of the implementation method. Accelerated aging testing also showed that under extreme conditions (40°C, 80% relative humidity) for 90 days, the barrier performance of the superhydrophobic interface micro-structure decreased by no more than 15%, completely consistent with the description of the implementation method.

[0108] These results fully demonstrate that the superhydrophobic interface micro-region structure can effectively block water molecules from penetrating to the interface (water resistance > 95%), thereby preventing water molecule-mediated ion migration and biodegradation, and providing a long-term stable protective layer for the composite membrane. This technology achieves highly efficient water molecule blocking by precisely controlling the solvent evaporation rate, utilizing the self-assembly of hydrophobic groups to form nanoscale superhydrophobic micro-regions, and forming a stable structure (completely consistent with claim 11) through heat treatment at 120-130℃ for 5-10 minutes.

[0109] The embodiments of the present invention have been described above. However, the embodiments are not limited to the specific implementation methods described above. The specific implementation methods described above are merely illustrative and not restrictive. Those skilled in the art can make more equivalent embodiments under the guidance of the present embodiments, and all of them are within the protection scope of the present embodiments.

Claims

1. A process for preparing a high-barrier composite film for pharmaceuticals, comprising the preparation of a biodegradable substrate, the preparation of an inorganic barrier layer, and a post-processing step for the composite film, characterized in that, The process also includes the following steps: A bio-based pressure-sensitive adhesive containing an enzyme activity inhibitor is coated on a biodegradable substrate, wherein the concentration of the enzyme activity inhibitor increases layer by layer from the biodegradable substrate side to the inorganic barrier layer side, forming a concentration gradient distribution structure. The surface of a biodegradable substrate coated with a bio-based pressure-sensitive adhesive is subjected to low-temperature plasma treatment and then immersed in a multivalent metal salt solution to form exchangeable ions on the surface. A solution of macromolecular chains with multiple coordination groups is sprayed onto the surface of an ion-modified substrate, so that the coordination macromolecular chains form coordination complexes with surface metal ions to construct an ion immobilization network. An inorganic barrier layer and an ion-fixed network layer are laminated and cured under a temperature and humidity gradient, wherein the temperature and humidity gradient is as follows: the temperature on the biodegradable substrate side is 60-70℃ and the relative humidity is 20-30%, and the temperature on the inorganic barrier layer side is 30-40℃ and the relative humidity is 70-80%. A superhydrophobic modified chitosan solution is sprayed onto the surface of the cured composite film. The solvent evaporation rate is controlled to allow the hydrophobic groups to self-assemble into a superhydrophobic micro-region structure. Then, a stable phase interface dehydration protective layer is formed by heat treatment.

2. The preparation process of the high-barrier composite membrane for pharmaceuticals according to claim 1, characterized in that, The biodegradable substrate is selected from one or more of polylactic acid, polycaprolactone, or polyhydroxyalkanoates.

3. The preparation process of the high-barrier composite membrane for pharmaceuticals according to claim 1, characterized in that, The bio-based pressure-sensitive adhesive is prepared by mixing rosin ester resin (obtained by reacting natural rosin with polyols) with vegetable oil, and then adding a diisocyanate crosslinking agent.

4. The preparation process of the high-barrier composite membrane for pharmaceuticals according to claim 1, characterized in that, The enzyme activity inhibitor is selected from one or more of curcumin, green tea polyphenols, and rosemary extract.

5. The preparation process of the high-barrier composite membrane for pharmaceuticals according to claim 1, characterized in that, The concentration gradient of the enzyme activity inhibitor is as follows: 0.5% for the first layer, 1.0% for the second layer, 2.0% for the third layer, and 5.0% for the fourth layer, with each layer having a thickness of 1-2 μm.

6. The preparation process of the high-barrier composite membrane for pharmaceuticals according to claim 1, characterized in that, The multivalent metal salt is selected from one or more of calcium chloride, zinc chloride, and magnesium chloride.

7. The preparation process according to claim 1, characterized in that, The macromolecular chain having multiple coordinating groups is selected from one or more of carboxymethyl cellulose, sodium alginate, and polyacrylic acid.

8. The preparation process of the high-barrier composite membrane for pharmaceuticals according to claim 1, characterized in that, The inorganic barrier layer is made of one or more of alumina, silicon oxide, and zinc oxide.

9. The preparation process of the high-barrier composite membrane for pharmaceuticals according to claim 1, characterized in that, The thickness of the inorganic barrier layer is 10-100 nm.

10. The preparation process of the high-barrier composite membrane for pharmaceuticals according to claim 1, characterized in that, The superhydrophobic modified chitosan is prepared by hydrophobic modification of chitosan with octadecyl isocyanate, and the water contact angle of the superhydrophobic micro-region structure is not less than 150°.

11. The preparation process of the high-barrier composite membrane for pharmaceuticals according to claim 1, characterized in that, The heat treatment is performed at a temperature of 120-130℃ for 5-10 minutes.

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