Preparation method of damp-proof and antibacterial medicine packaging composite material with multiple barrier functions

Abstract

The invention relates to a preparation method of a damp-proof antibacterial medicine packaging composite material with multiple barrier functions, and belongs to the technical field of medicine packaging materials. Enabling the composite complexing nano-silver, polyethylene and zinc stearate to pass through a double-screw extruder to obtain nano-silver antibacterial master batches; adding the nano-silver antibacterial master batch, a mixture of linear polyethylene and an ethylene-vinyl alcohol copolymer, an antioxidant 1010 and silicon dioxide into a single-screw extruder to obtain a damp-proof antibacterial film layer; uniformly coating a polyurethane adhesive on the surface of the damp-proof and antibacterial film layer, compounding an aluminum foil and the film layer coated with the adhesive on a compounding machine, and curing to obtain an aluminum foil-damp-proof and antibacterial film layer; the surface of the aluminum foil-damp-proof antibacterial film layer is coated with a polyurethane adhesive, and then the aluminum foil-damp-proof antibacterial film layer is compounded with a biaxially oriented polypropylene film and cured. The packaging composite material prepared by the invention has excellent moisture resistance, antibacterial ability, barrier property and mechanical property.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical packaging materials, in particular to a method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions. Background Art

[0002] Pharmaceuticals are often chemically active and easily affected by external environmental factors such as moisture, oxygen, and microorganisms. For example, some antibiotics are prone to hydrolysis in humid environments, resulting in reduced efficacy. Drugs containing unsaturated bonds are easily oxidized by oxygen, causing deterioration. Therefore, pharmaceutical packaging materials must possess excellent barrier properties to prevent external factors from eroding the drugs and ensure the stability of their quality throughout their shelf life.

[0003] Chinese Patent CN119431746A relates to the field of pharmaceutical packaging, specifically cycloolefin polymer hydrides, resin compositions, resin molded articles, and pharmaceutical packaging materials. The cycloolefin polymer hydrides provided by the present invention, wherein the repeating units of monocyclic structures and repeating units containing bridged ring structures are present in specific proportions, exhibit high moisture and grease resistance, and exhibit good flowability during further melt molding into resin molded articles. Furthermore, the polymer hydrides have low residual metal content and a relatively high glass transition temperature, making them highly suitable for use in the preparation of pharmaceutical packaging materials.

[0004] Chinese patent CN119039744A: discloses a method for preparing medical packaging materials from degradable plastics, relating to the technical field of packaging materials; includes S1-S7; by modifying PBS during the preparation process, the PBS is made to have good flexibility, the film-forming effect of the prepared medical packaging material is improved, and the degradation performance and barrier properties of the medical packaging material are improved; by modifying PBS and degradable polyester during the preparation process, the compatibility between the degradable polyester and PBS is improved, the binding force of the two phases is enhanced, and the preparation efficiency of the medical packaging material is improved; by adding antioxidants and antibacterial agents during the preparation process, the medical packaging material has good antioxidant and antibacterial properties, which can effectively inhibit the generation of free radicals and reduce the occurrence of oxidation reactions, thereby improving the antioxidant and antibacterial properties of the medical packaging material.

[0005] Chinese patent CN106147084A: discloses an antibacterial pharmaceutical packaging material and a preparation method thereof. The antibacterial pharmaceutical packaging material is made of the following raw materials in parts by weight: 20-45 parts of polyvinyl chloride, 12-25 parts of permethrin, 8-18 parts of polyethylene terephthalate, 3-10 parts of nano-titanium dioxide, 2-8 parts of nano-silver, 12-25 parts of polyimide, 10-22 parts of polyglycolic acid, 3-8 parts of zinc oxide, 5-12 parts of acrylamide, 3-10 parts of ammonium dihydrogen phosphate, 6-14 parts of polyester fiber, 1-2.5 parts of trichlorofluoromethane, 2.5-7 parts of polyethersulfone, 4-11 parts of diphenyldichlorosilane, 2-7 parts of calcium carbonate, 2-6 parts of titanate coupling agent, 5-12 parts of dicumyl peroxide, 3-9 parts of calcium alkylbenzene sulfonate, 2-8 parts of dimethylaminopropylamine, and 3-13 parts of ethylene-vinyl acetate copolymer.

[0006] Existing pharmaceutical packaging materials, such as ordinary plastic film and paper packaging, have relatively weak moisture-proof properties. In high-humidity environments, such as shipping, storage, and transportation in humid areas, moisture can easily penetrate the packaging material, causing the drugs to clump and deteriorate.

[0007] Lack of antimicrobial properties: Typical packaging materials lack inherent antimicrobial properties and are unable to inhibit the growth and reproduction of microorganisms within the packaging. During production, storage, and transportation, pharmaceuticals may come into contact with various microorganisms. If the packaging materials are not effective in resisting microorganisms, microorganisms may grow within the packaging, contaminating the pharmaceuticals and affecting their safety and effectiveness. Summary of the Invention

[0008] In order to solve the above problems, the present invention provides a method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions, the operating steps of which are as follows:

[0009] S1. Preparation of antibacterial masterbatch: 1-5 parts of composite complex nanosilver with a particle size of 20-50 nanometers, 35-45 parts of polyethylene, and 0.1-0.5 parts of dispersant zinc stearate are stirred and uniformly mixed; using a twin-screw extruder, the nanosilver antibacterial masterbatch is obtained by thorough mixing and extrusion granulation;

[0010] S2: Preparation of moisture-proof and antibacterial film layer: 1-5 parts of nano-silver antibacterial masterbatch, 75-95 parts of a mixture of linear polyethylene and ethylene-vinyl alcohol copolymer, 0.2-0.5 parts of antioxidant 1010, and 0.3-0.6 parts of anti-blocking silica with a particle size of 10-20 μm are added to a single-screw extruder and extruded through a T-die to form a moisture-proof and antibacterial film layer with a thickness of 30-40 μm. During the extrusion process, a stable screw speed of 150-200 rpm and a melt pressure of 8-12 MPa are maintained to ensure uniform film thickness.

[0011] S3 aluminum foil lamination: Using a dry lamination process, the extruded moisture-proof and antibacterial film layer is laminated with aluminum foil with a thickness of 10-15 microns. First, a polyurethane adhesive is evenly coated on the surface of the moisture-proof and antibacterial film layer at a coating amount of 3-5 grams per square meter. The aluminum foil and the adhesive-coated film layer are then laminated on a laminating machine at a lamination temperature of 60-70°C and a lamination pressure of 0.3-0.5 MPa. After lamination, the materials are aged at 40-50°C for 24-48 hours to fully cure the adhesive and ensure a firm bond between the aluminum foil and the moisture-proof and antibacterial film layer.

[0012] Preparation of S4 outer protective layer: A biaxially oriented polypropylene film with a thickness of 20-30 microns is selected as the outer protective layer; a dry composite process is used to apply a thin layer of polyurethane adhesive on the surface of the composite aluminum foil-moisture-proof and antibacterial film layer, with a coating amount of 2-3 g / m2; then it is composited with the biaxially oriented polypropylene film at a composite temperature of 50-60°C and a composite pressure of 0.2-0.4 MPa; after composite, it is aged at 35-45°C for 12-24 hours to obtain a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions.

[0013] As a preferred embodiment of the present invention, the feeding section temperature of the twin-screw extruder is 160-170°C, the compression section temperature is 170-180°C, the metering section temperature is 180-190°C, the die head temperature is 190-200°C, and the screw speed is 200-300 rpm.

[0014] As a preferred embodiment of the present invention, the mixture of linear polyethylene and ethylene-vinyl alcohol copolymer has a mass ratio of 5-7:3.

[0015] As a preferred embodiment of the present invention, the temperature of the feeding section of the single-screw extruder is 150-160°C, the temperature of the plasticizing section is 160-170°C, the temperature of the homogenizing section is 170-180°C, and the die head temperature is 180-190°C.

[0016] As a preferred embodiment of the present invention, the preparation method of the composite complexed nanosilver is:

[0017] A1: Mix reactants in a clean glass reaction container. Measure and add the corresponding solutions of nanosilver-thioglycolic acid coordination complex: polyoxyethylene diamine: ficin: citrate buffer in a mass ratio of 0.5:1-2:1:0.004-0.05:100-120.

[0018] A2 performs acylation reaction: Place the reaction vessel in a thermostatic shaker and stir continuously at 100-300 rpm at a temperature of 30-37°C for 4-8 hours;

[0019] A3 Post-treatment: After the reaction is completed, select an ultrafiltration membrane with a molecular weight cutoff of 10-100 kDa, centrifuge and ultrafilter at a speed of 3000-5000 rpm for 10-30 minutes, and distill to remove the liquid to obtain composite complexed nanosilver.

[0020] As a preferred embodiment of the present invention, the preparation method of the nano silver-thioglycolic acid coordination complex is:

[0021] H1: Add silver nanoparticles to thioglycolic acid in a molar ratio of 1:5-1:20 into a clean glass reaction vessel. Place the reaction vessel on a magnetic stirrer and stir at 200-500 rpm for 1-3 hours at room temperature (20-25°C) to allow for a complete complexation reaction.

[0022] H2 separation and purification complex: After the complexation reaction is completed, the reaction solution is transferred to a centrifuge tube and centrifuged at a speed of 5000-10000 rpm for 10-30 minutes. The precipitate is washed 2-3 times with deionized water to obtain a nanosilver-thioglycolic acid coordination complex.

[0023] Reaction mechanism

[0024] Formation of the nanosilver-thioglycolic acid coordination complex: In the thioglycolic acid (HS-CH2-COOH) molecule, the sulfur atom on the thiol group (-SH) has a lone pair of electrons, while the silver atoms on the surface of the nanosilver particles have empty orbitals. According to the principles of coordination chemistry, the lone pair of electrons of the sulfur atom fills the empty orbitals of the silver atoms, forming a coordination bond. This coordination effect allows the thioglycolic acid to bind tightly to the surface of the nanosilver particles, forming the nanosilver-thioglycolic acid coordination complex.

[0025] Formation of the composite silver nanocomplex: In the stable acid-base environment provided by citrate buffer, the carboxyl groups (-COOH) in the silver nanocomplex-thioglycolic acid coordination complex exhibit a certain degree of electrophilicity. The amino groups (-NH2) at both ends of the polyoxyethylenediamine molecule are nucleophilic reagents. The nitrogen atom on the amino group carries a lone pair of electrons and attacks the carbonyl carbon atom in the carboxyl group, causing a nucleophilic addition-elimination reaction, i.e., an acylation reaction, to form an amide bond (-CONH-).

[0026] At the same time, the active groups on the ficin molecule (such as amino, carboxyl, etc.) will also participate in a similar acylation reaction, thereby connecting polyoxyethylene diamine and ficin to the nanosilver-thioglycolic acid coordination complex to form a composite complex nanosilver.

[0027] Technical Effects

[0028] The present invention provides a method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions. Compared with the prior art, the present invention has the following significant effects:

[0029] 1. Anti-agglomeration: The complexation of thioglycolic acid with the nanosilver particles, followed by the subsequent connection with polyoxyethylene diamine and ficin, creates a multilayered structure on the surface of the nanosilver particles. Thioglycolic acid initially forms a first layer of coating on the surface of the nanosilver particles, increasing the steric hindrance between the particles and hindering direct contact between the nanosilver particles. The subsequent connection with polyoxyethylene diamine and ficin further increases the steric hindrance. These hydrophilic molecules form a hydration layer around the nanosilver particles, effectively preventing the nanosilver particles from agglomerating and maintaining their stable dispersion in the solution.

[0030] 2. Multifunctionality: Polyoxyethylene diamine increases the hydrophilicity and modifiability of the complex. The hydrophilicity makes the composite complexed nanosilver have good dispersibility and compatibility in the body or in aqueous solution, which is conducive to its application in the biomedical field.

[0031] 3. Improved barrier effect: The formation of the nanosilver-thioglycolic acid coordination complex has a positive impact on the barrier properties of the subsequently prepared packaging materials. On the one hand, the coating formed by thioglycolic acid on the surface of the nanosilver changes the surface properties of the nanosilver particles, making them more compatible with the packaging material matrix (such as polyethylene) and more evenly dispersed within the matrix. Evenly dispersed nanosilver particles can form more tortuous paths within the packaging material. When gases (such as oxygen and carbon dioxide) or water molecules attempt to penetrate the packaging material, they need to bypass these nanosilver particles, thereby increasing their diffusion path length, effectively reducing the permeability of gases and moisture, and improving the barrier properties of the packaging material. DETAILED DESCRIPTION

[0032] In order to further illustrate the technical means and effects adopted by the present invention to achieve the predetermined purpose of the invention, the specific implementation methods, structures, features and effects of the present invention are described in detail below in combination with preferred embodiments.

[0033] 1. Antibacterial performance test: Using the plate colony counting method, the composite material was cut into samples of a certain size and placed in a culture medium containing Escherichia coli and Staphylococcus aureus. After incubation at 37°C for 24 hours, the colony growth on the culture medium was observed and the antibacterial rate was calculated.

[0034] 2. Moisture-proof performance test: Using the moisture-permeable cup method, seal the composite material in a moisture-permeable cup filled with desiccant and place it in an environment with a temperature of 38°C and a relative humidity of 90%. Measure the weight change of the moisture-permeable cup over a certain period of time and calculate the water vapor transmission rate.

[0035] 3. Barrier performance test: Use differential pressure gas permeometer to test the barrier performance of composite materials to oxygen.

[0036] 4. Mechanical properties testing: Use a universal material testing machine to test the tensile strength of the composite material.

[0037] Example 1

[0038] A method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions, the operating steps of which are as follows:

[0039] Preparation of S1 antibacterial masterbatch: 1g of composite complex nanosilver with a particle size of 20 nanometers, 35g of polyethylene, and 0.1g of dispersant zinc stearate were stirred and uniformly mixed; a twin-screw extruder was used to obtain nanosilver antibacterial masterbatch through thorough mixing and extrusion granulation;

[0040] Preparation of S2 moisture-proof and antibacterial film layer: 1 g of nano-silver antibacterial masterbatch, 75 g of a mixture of linear polyethylene and ethylene-vinyl alcohol copolymer, 0.2 g of antioxidant 1010, and 0.3 g of 10 μm particle size anti-blocking agent silica were added to a single-screw extruder and extruded through a T-die to form a moisture-proof and antibacterial film layer with a thickness of 30 μm. During the extrusion process, a stable screw speed of 150 rpm and a melt pressure of 8 MPa were maintained to ensure uniform film thickness.

[0041] S3 aluminum foil lamination: Using a dry lamination process, an extruded moisture-proof and antibacterial film layer is laminated with a 10-micron-thick aluminum foil. First, a polyurethane adhesive is evenly coated on the surface of the moisture-proof and antibacterial film layer at a coating amount of 3 grams per square meter. The aluminum foil and the adhesive-coated film layer are then laminated on a laminating machine at a lamination temperature of 60°C and a lamination pressure of 0.3 MPa. After lamination, the materials are aged at 40°C for 24 hours to fully cure the adhesive and ensure a firm bond between the aluminum foil and the moisture-proof and antibacterial film layer.

[0042] Preparation of S4 outer protective layer: A biaxially oriented polypropylene film with a thickness of 20 microns was selected as the outer protective layer; a dry composite process was used to apply a thin layer of polyurethane adhesive on the surface of the composite aluminum foil-moisture-proof and antibacterial film layer, with a coating amount of 2 grams per square meter; then the composite was composited with the biaxially oriented polypropylene film at a composite temperature of 50°C and a composite pressure of 0.2 MPa; after composite, the composite was aged at 35°C for 12 hours to obtain a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions.

[0043] The feeding section temperature of the twin-screw extruder is 160°C, the compression section temperature is 170°C, the metering section temperature is 180°C, the die head temperature is 190°C, and the screw speed is 200 rpm.

[0044] The mass ratio of the mixture of linear polyethylene and ethylene-vinyl alcohol copolymer is 5:3.

[0045] The temperature of the feeding section of the single-screw extruder is 150°C, the temperature of the plasticizing section is 160°C, the temperature of the homogenizing section is 170°C, and the temperature of the die head is 180°C.

[0046] The preparation method of the composite complexed nanosilver is as follows:

[0047] A1: Mix reactants in a clean glass reaction container. Measure and add the corresponding solutions of nanosilver-thioglycolic acid coordination complex, polyoxyethylene diamine, ficin, and citrate buffer (CAS No. 13754-17-1) in a mass ratio of 0.5:1:1:0.004:100.

[0048] A2: Acylation reaction was carried out by placing the reaction vessel in a thermostatic shaker at 30°C and stirring at 100 rpm for 4 hours.

[0049] A3 Post-treatment: After the reaction is completed, select an ultrafiltration membrane with a molecular weight cutoff of 10 kDa, centrifuge and ultrafilter at a speed of 3000 rpm for 10 minutes, and distill to remove the liquid to obtain composite complexed nanosilver.

[0050] The preparation method of the nano silver-thioglycolic acid coordination complex is as follows:

[0051] H1: Add silver nanoparticles to thioglycolic acid in a molar ratio of 1:5 into a clean glass reaction vessel. Place the reaction vessel on a magnetic stirrer and stir at 200 rpm for 1 hour at room temperature (20°C) to allow for a complete complexation reaction.

[0052] H2 separation and purification of the complex: After the complexation reaction is completed, the reaction solution is transferred to a centrifuge tube, centrifuged at 5000 rpm for 10 minutes, and the precipitate is washed twice with deionized water to obtain the nanosilver-thioglycolic acid coordination complex.

[0053] Example 2

[0054] A method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions, the operating steps of which are as follows:

[0055] Preparation of S1 antibacterial masterbatch: 2g of composite complex nanosilver with a particle size of 30 nanometers, 38g of polyethylene, and 0.2g of dispersant zinc stearate were stirred and uniformly mixed; using a twin-screw extruder, the nanosilver antibacterial masterbatch was obtained by thorough mixing and extrusion granulation;

[0056] Preparation of S2 moisture-proof and antibacterial film layer: 2 g of nano-silver antibacterial masterbatch, 80 g of a mixture of linear polyethylene and ethylene-vinyl alcohol copolymer, 0.3 g of antioxidant 1010, and 0.4 g of 15 μm particle size anti-blocking agent silica were added to a single-screw extruder and extruded through a T-die to form a moisture-proof and antibacterial film layer with a thickness of 35 μm. During the extrusion process, a stable screw speed of 160 rpm and a melt pressure of 9 MPa were maintained to ensure uniform film thickness.

[0057] S3 aluminum foil lamination: Using a dry lamination process, an extruded moisture-proof and antibacterial film layer is laminated with a 12-micron-thick aluminum foil. First, a polyurethane adhesive is evenly coated on the surface of the moisture-proof and antibacterial film layer at a coating amount of 4 grams per square meter. The aluminum foil and the adhesive-coated film layer are then laminated on a laminating machine at a lamination temperature of 65°C and a lamination pressure of 0.4 MPa. After lamination, the materials are aged at 45°C for 30 hours to fully cure the adhesive and ensure a firm bond between the aluminum foil and the moisture-proof and antibacterial film layer.

[0058] Preparation of S4 outer protective layer: A biaxially oriented polypropylene film with a thickness of 25 microns was selected as the outer protective layer; a dry composite process was used to apply a thin layer of polyurethane adhesive on the surface of the composite aluminum foil-moisture-proof and antibacterial film layer, with a coating amount of 2 grams / square meter; then it was composited with the biaxially oriented polypropylene film at a composite temperature of 55°C and a composite pressure of 0.3 MPa; after composited, it was aged at 8°C for 18 hours to obtain a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions.

[0059] The feeding section temperature of the twin-screw extruder is 165°C, the compression section temperature is 175°C, the metering section temperature is 185°C, the die head temperature is 195°C, and the screw speed is 250 rpm.

[0060] The mass ratio of the mixture of linear polyethylene and ethylene-vinyl alcohol copolymer is 6:3.

[0061] The temperature of the feeding section of the single-screw extruder is 155°C, the temperature of the plasticizing section is 165°C, the temperature of the homogenizing section is 175°C, and the temperature of the die head is 185°C.

[0062] The preparation method of the composite complexed nanosilver is as follows:

[0063] A1: Mix reactants in a clean glass reaction vessel. Measure and add the corresponding solutions of nanosilver-thioglycolic acid coordination complex, polyoxyethylene diamine, ficin, and citrate buffer (CAS No. 13754-17-1) in a mass ratio of 0.5:1.3:1:0.02:105.

[0064] A2 Acylation reaction: Place the reaction vessel in a thermostatic shaker and stir at 33°C and 200 rpm for 5 hours;

[0065] A3 Post-treatment: After the reaction is completed, select an ultrafiltration membrane with a molecular weight cutoff of 50 kDa, centrifuge and ultrafilter at a speed of 4000 rpm for 15 minutes, and distill to remove the liquid to obtain composite complexed nanosilver.

[0066] The preparation method of the nano silver-thioglycolic acid coordination complex is as follows:

[0067] H1: Add silver nanoparticles to thioglycolic acid in a molar ratio of 1:10 into a clean glass reaction vessel. Place the reaction vessel on a magnetic stirrer and stir at 300 rpm for 2 hours at room temperature (22°C) to allow for a complete complexation reaction.

[0068] H2 separation and purification of the complex: After the complexation reaction is completed, the reaction solution is transferred to a centrifuge tube and centrifuged at 6000 rpm for 15 minutes. The precipitate is washed twice with deionized water to obtain the nanosilver-thioglycolic acid coordination complex.

[0069] Example 3

[0070] A method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions, the operating steps of which are as follows:

[0071] Preparation of S1 antibacterial masterbatch: 4g of composite complex nanosilver with a particle size of 40 nanometers, 43g of polyethylene, and 0.4g of dispersant zinc stearate were stirred and uniformly mixed; using a twin-screw extruder, the nanosilver antibacterial masterbatch was obtained by thorough mixing and extrusion granulation;

[0072] Preparation of S2 moisture-proof and antibacterial film layer: 4 g of nano-silver antibacterial masterbatch, 90 g of a mixture of linear polyethylene and ethylene-vinyl alcohol copolymer, 0.4 g of antioxidant 1010, and 0.5 g of 15 μm particle size anti-blocking agent silica were added to a single-screw extruder and extruded through a T-die to form a moisture-proof and antibacterial film layer with a thickness of 35 μm. During the extrusion process, a stable screw speed of 180 rpm and a melt pressure of 11 MPa were maintained to ensure uniform film thickness.

[0073] S3 aluminum foil lamination: Using a dry lamination process, an extruded moisture-proof and antibacterial film layer is laminated with a 14-micron-thick aluminum foil. First, a polyurethane adhesive is evenly coated on the surface of the moisture-proof and antibacterial film layer at a coating amount of 4 grams per square meter. The aluminum foil and the adhesive-coated film layer are then laminated on a laminating machine at a lamination temperature of 65°C and a lamination pressure of 0.4 MPa. After lamination, the materials are aged at 45°C for 45 hours to fully cure the adhesive and ensure a firm bond between the aluminum foil and the moisture-proof and antibacterial film layer.

[0074] Preparation of S4 outer protective layer: A biaxially oriented polypropylene film with a thickness of 25 microns was selected as the outer protective layer; a dry composite process was used to apply a thin layer of polyurethane adhesive on the surface of the composite aluminum foil-moisture-proof and antibacterial film layer, with a coating amount of 3 g / m2; then the composite was composited with the biaxially oriented polypropylene film at a composite temperature of 55°C and a composite pressure of 0.3 MPa; after composite, the composite was aged at 43°C for 20 hours to obtain a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions.

[0075] The feeding section temperature of the twin-screw extruder is 165°C, the compression section temperature is 175°C, the metering section temperature is 185°C, the die head temperature is 195°C, and the screw speed is 250 rpm.

[0076] The mass ratio of the mixture of linear polyethylene and ethylene-vinyl alcohol copolymer is 6:3.

[0077] The temperature of the feeding section of the single-screw extruder is 155°C, the temperature of the plasticizing section is 165°C, the temperature of the homogenizing section is 175°C, and the temperature of the die head is 185°C.

[0078] The preparation method of the composite complexed nanosilver is as follows:

[0079] A1: Mix reactants in a clean glass reaction vessel. Measure and add the corresponding solutions of nanosilver-thioglycolic acid coordination complex, polyoxyethylene diamine, ficin, and citrate buffer (CAS No. 13754-17-1) in a mass ratio of 0.5:1.8:1:0.04:115.

[0080] A2: Acylation reaction was carried out by placing the reaction vessel in a thermostatic shaker at 36°C and stirring at 200 rpm for 7 hours.

[0081] A3 Post-treatment: After the reaction is completed, select an ultrafiltration membrane with a molecular weight cutoff of 80 kDa, centrifuge and ultrafilter at a speed of 4000 rpm for 25 minutes, and distill to remove the liquid to obtain composite complexed nanosilver.

[0082] The preparation method of the nano silver-thioglycolic acid coordination complex is as follows:

[0083] H1: Add silver nanoparticles to thioglycolic acid in a molar ratio of 1:15 into a clean glass reaction vessel. Place the reaction vessel on a magnetic stirrer and stir at 400 rpm for 2 hours at room temperature (24°C) to allow for a complete complexation reaction.

[0084] H2 separation and purification of the complex: After the complexation reaction is completed, the reaction solution is transferred to a centrifuge tube and centrifuged at 8000 rpm for 25 minutes. The precipitate is washed three times with deionized water to obtain the nanosilver-thioglycolic acid coordination complex.

[0085] Example 4

[0086] A method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions, the operating steps of which are as follows:

[0087] Preparation of S1 antibacterial masterbatch: 5g of composite complex nanosilver with a particle size of 50 nanometers, 45g of polyethylene, and 0.5g of dispersant zinc stearate were stirred and uniformly mixed; using a twin-screw extruder, the nanosilver antibacterial masterbatch was obtained by thorough mixing and extrusion granulation;

[0088] Preparation of S2 moisture-proof and antibacterial film layer: 5 g of nano-silver antibacterial masterbatch, 95 g of a mixture of linear polyethylene and ethylene-vinyl alcohol copolymer, 0.5 g of antioxidant 1010, and 0.6 g of 20 μm particle size anti-blocking agent silica were added to a single-screw extruder and extruded through a T-die to form a moisture-proof and antibacterial film layer with a thickness of 40 μm. During the extrusion process, a stable screw speed of 200 rpm and a melt pressure of 12 MPa were maintained to ensure uniform film thickness.

[0089] S3 aluminum foil lamination: Using a dry lamination process, the extruded moisture-proof and antibacterial film layer is laminated with a 15-micron-thick aluminum foil. First, a polyurethane adhesive is evenly coated on the surface of the moisture-proof and antibacterial film layer at a coating amount of 5 grams per square meter. The aluminum foil and the adhesive-coated film layer are then laminated on a laminating machine at a lamination temperature of 70°C and a lamination pressure of 0.5 MPa. After lamination, the materials are aged at 50°C for 48 hours to fully cure the adhesive and ensure a firm bond between the aluminum foil and the moisture-proof and antibacterial film layer.

[0090] Preparation of S4 outer protective layer: A biaxially oriented polypropylene film with a thickness of 30 microns was selected as the outer protective layer; a dry composite process was used to apply a thin layer of polyurethane adhesive on the surface of the composite aluminum foil-moisture-proof and antibacterial film layer, with a coating amount of 3 g / m2; then the composite was composited with the biaxially oriented polypropylene film at a composite temperature of 60°C and a composite pressure of 0.4 MPa; after composite, the composite was aged at 45°C for 24 hours to obtain a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions.

[0091] The feeding section temperature of the twin-screw extruder is 170°C, the compression section temperature is 180°C, the metering section temperature is 190°C, the die head temperature is 200°C, and the screw speed is 300 rpm.

[0092] The mass ratio of the mixture of linear polyethylene and ethylene-vinyl alcohol copolymer is 7:3.

[0093] The temperature of the feeding section of the single-screw extruder is 160°C, the temperature of the plasticizing section is 170°C, the temperature of the homogenizing section is 180°C, and the temperature of the die head is 190°C.

[0094] The preparation method of the composite complexed nanosilver is as follows:

[0095] A1: Mix reactants in a clean glass reaction vessel. Measure and add the corresponding solutions of nanosilver-thioglycolic acid coordination complex, polyoxyethylene diamine, ficin, and citrate buffer (CAS No. 13754-17-1) in a mass ratio of 0.5:2:1:0.05:120.

[0096] A2: Acylation reaction was carried out by placing the reaction vessel in a thermostatic shaker at 37°C and stirring at 300 rpm for 8 hours.

[0097] A3 Post-treatment: After the reaction is completed, an ultrafiltration membrane with a molecular weight cut-off of 100 kDa is selected, and ultrafiltration is performed at a speed of 5000 rpm for 30 minutes. The liquid is distilled off to obtain composite complexed nanosilver.

[0098] The preparation method of the nano silver-thioglycolic acid coordination complex is as follows:

[0099] H1: Add silver nanoparticles to thioglycolic acid at a molar ratio of 1:20 into a clean glass reaction vessel. Place the reaction vessel on a magnetic stirrer and stir at 500 rpm for 3 hours at 25°C to allow for a complete complexation reaction.

[0100] H2 separation and purification complex: After the complexation reaction is completed, the reaction solution is transferred to a centrifuge tube, centrifuged at a speed of 10,000 rpm for 30 minutes, and the precipitate is washed three times with deionized water to obtain the nanosilver-thioglycolic acid coordination complex.

[0101] Comparative Example 1

[0102] Without adding the composite complexed nanosilver, nanosilver was added, and the rest was the same as in Example 1.

[0103] Comparative Example 2

[0104] The nano silver-thioglycolic acid coordination complex was not added, and the other steps were the same as in Example 1.

[0105] Comparative Example 3

[0106] Without adding polyoxyethylene diamine, the other steps were the same as in Example 1.

[0107] Table 1: Test data results of examples and comparative examples

[0108]

[0109]

[0110] Through the data analysis of the above examples and comparative examples, the moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions prepared by the present invention has excellent moisture-proof performance, outstanding antibacterial ability, excellent barrier performance, and good mechanical properties.

[0111] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Although the present invention has been disclosed as above in terms of a preferred embodiment, it is not intended to limit the present invention. Any person skilled in the art can, without departing from the scope of the technical solution of the present invention, make some changes or modifications to equivalent embodiments using the technical contents disclosed above. However, any brief modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions, the operating steps of which are as follows: S1. Preparation of antibacterial masterbatch: 1-5 parts of composite complex nanosilver with a particle size of 20-50 nanometers, 35-45 parts of polyethylene, and 0.1-0.5 parts of dispersant zinc stearate are stirred and uniformly mixed; using a twin-screw extruder, the nanosilver antibacterial masterbatch is obtained by thorough mixing and extrusion granulation; S2: Preparation of moisture-proof and antibacterial film layer: 1-5 parts of nano-silver antibacterial masterbatch, 75-95 parts of a mixture of linear polyethylene and ethylene-vinyl alcohol copolymer, 0.2-0.5 parts of antioxidant 1010, and 0.3-0.6 parts of anti-blocking silica with a particle size of 10-20 μm are added to a single-screw extruder and extruded through a T-die to form a moisture-proof and antibacterial film layer with a thickness of 30-40 μm. During the extrusion process, a stable screw speed of 150-200 rpm and a melt pressure of 8-12 MPa are maintained to ensure uniform film thickness. S3 aluminum foil lamination: Using a dry lamination process, the extruded moisture-proof and antibacterial film layer is laminated with aluminum foil with a thickness of 10-15 microns. First, a polyurethane adhesive is evenly coated on the surface of the moisture-proof and antibacterial film layer at a coating amount of 3-5 grams per square meter. The aluminum foil and the adhesive-coated film layer are then laminated on a laminating machine at a lamination temperature of 60-70°C and a lamination pressure of 0.3-0.5 MPa. After lamination, the materials are aged at 40-50°C for 24-48 hours to fully cure the adhesive and ensure a firm bond between the aluminum foil and the moisture-proof and antibacterial film layer. Preparation of S4 Outer Protective Layer: A biaxially oriented polypropylene film with a thickness of 20-30 microns is selected as the outer protective layer. Using a dry lamination process, a thin layer of polyurethane adhesive is applied to the surface of the laminated aluminum foil-moisture-proof and antibacterial film layer at a coating amount of 2-3 g / m2. The layer is then laminated with the biaxially oriented polypropylene film at a lamination temperature of 50-60°C and a lamination pressure of 0.2-0.4 MPa. After lamination, the layer is aged at 35-45°C for 12-24 hours to obtain a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions. The composite complex nano silver is prepared by reacting a nano silver-thioglycolic acid coordination complex, polyoxyethylene diamine, ficin and citrate buffer.

2. The method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions according to claim 1, characterized in that: The feeding section temperature of the twin-screw extruder is 160-170°C, the compression section temperature is 170-180°C, the metering section temperature is 180-190°C, the die head temperature is 190-200°C, and the screw speed is 200-300 rpm.

3. The method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions according to claim 1, characterized in that: The mass ratio of the mixture of linear polyethylene and ethylene-vinyl alcohol copolymer is 5-7:

3.

4. The method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions according to claim 1, characterized in that: The temperature of the feeding section of the single-screw extruder is 150-160°C, the temperature of the plasticizing section is 160-170°C, the temperature of the homogenizing section is 170-180°C, and the temperature of the die head is 180-190°C.

5. The method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions according to claim 1, characterized in that: The preparation method of the composite complexed nanosilver is as follows: A1: Mix reactants in a clean glass reaction container. Measure and add the corresponding solutions of nanosilver-thioglycolic acid coordination complex: polyoxyethylene diamine: ficin: citrate buffer in a mass ratio of 0.5:1-2:1:0.004-0.05:100-120. A2 performs acylation reaction: Place the reaction vessel in a thermostatic shaker and stir continuously at 100-300 rpm at a temperature of 30-37°C for 4-8 hours; A3 Post-treatment: After the reaction is completed, select an ultrafiltration membrane with a molecular weight cutoff of 10-100 kDa, centrifuge and ultrafilter at a speed of 3000-5000 rpm for 10-30 minutes, and distill to remove the liquid to obtain composite complexed nanosilver.

6. The method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions according to claim 5, characterized in that: The preparation method of the nano silver-thioglycolic acid coordination complex is as follows: H1: Add silver nanoparticles to thioglycolic acid in a molar ratio of 1:5-1:20 into a clean glass reaction vessel. Place the reaction vessel on a magnetic stirrer and stir at 200-500 rpm for 1-3 hours at room temperature (20-25°C) to allow for a complete complexation reaction. H2 separation and purification complex: After the complexation reaction is completed, the reaction solution is transferred to a centrifuge tube and centrifuged at a speed of 5000-10000 rpm for 10-30 minutes. The precipitate is washed 2-3 times with deionized water to obtain a nanosilver-thioglycolic acid coordination complex.

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