A method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions

Abstract

This invention relates to a method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions, belonging to the technical field of pharmaceutical packaging materials. The method involves extruding a composite complex of nano-silver, polyethylene, and zinc stearate through a twin-screw extruder to obtain a nano-silver antibacterial masterbatch. A mixture of the nano-silver antibacterial masterbatch, linear polyethylene and ethylene-vinyl alcohol copolymer, antioxidant 1010, and silica are then added to a single-screw extruder to obtain a moisture-proof and antibacterial film layer. A polyurethane adhesive is uniformly coated onto the surface of the moisture-proof and antibacterial film layer. An aluminum foil is then laminated with the adhesive-coated film layer on a laminating machine and cured to obtain an aluminum foil-moisture-proof and antibacterial film layer. Finally, a polyurethane adhesive is coated onto the surface of the aluminum foil-moisture-proof and antibacterial film layer, which is then laminated with a biaxially oriented polypropylene film and cured. The packaging composite material prepared by this invention exhibits excellent moisture-proof performance, antibacterial ability, barrier properties, and mechanical properties.

Description

Technical Field

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

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

[0003] Chinese Patent CN119431746A relates to the field of pharmaceutical packaging, specifically cyclic olefin polymer hydrides, resin compositions, resin molded articles, and pharmaceutical packaging materials. The cyclic olefin polymer hydrides provided by this invention, wherein the repeating units with monocyclic structures and repeating units containing bridged ring structures, at a specific content ratio, exhibit high moisture and oil resistance. Furthermore, during the further melt molding process to form a resin molded article, it demonstrates good flowability, low metal residue, and a relatively high glass transition temperature, making it highly suitable for application in the preparation of pharmaceutical packaging materials.

[0004] Chinese Patent CN119039744A discloses a method for preparing pharmaceutical packaging materials from biodegradable plastics, relating to the field of packaging materials technology; including steps S1-S7; by modifying PBS during the preparation process, PBS is made to have good flexibility, improving the film-forming effect of the prepared medical packaging material, and at the same time improving the degradation performance and barrier properties of the medical packaging material; by modifying PBS and biodegradable polyester during the preparation process, the compatibility between biodegradable polyester and PBS is improved, the bonding force between 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 its preparation method. The antibacterial pharmaceutical packaging material is made from the following raw materials in parts by weight: 20-45 parts polyvinyl chloride, 12-25 parts permethrin, 8-18 parts polyethylene terephthalate, 3-10 parts nano titanium dioxide, 2-8 parts nano silver, 12-25 parts polyimide, 10-22 parts polyglycolic acid, 3-8 parts zinc oxide, 5-12 parts acrylamide, 3-10 parts ammonium dihydrogen phosphate, 6-14 parts polyester fiber, 1-2.5 parts trichlorofluoromethane, 2.5-7 parts polyethersulfone, 4-11 parts diphenyl dichlorosilane, 2-7 parts calcium carbonate, 2-6 parts titanate coupling agent, 5-12 parts dicumyl peroxide, 3-9 parts calcium alkylbenzene sulfonate, 2-8 parts dimethylaminopropylamine, and 3-13 parts ethylene-vinyl acetate copolymer.

[0006] Existing pharmaceutical packaging materials, such as ordinary plastic films and paper packaging, have relatively weak moisture-proof properties. In high-humidity environments, such as sea freight, warehousing and transportation in humid areas, moisture can easily penetrate the packaging material and enter the interior, causing the medicine to become damp, clump, and deteriorate.

[0007] Insufficient antibacterial properties: General packaging materials do not possess antibacterial functions and cannot inhibit the growth and reproduction of microorganisms inside the packaging. During the production, storage, and transportation of pharmaceuticals, they may come into contact with various microorganisms. If the packaging materials are not effectively antibacterial, microorganisms may proliferate inside the packaging, thereby contaminating the pharmaceuticals and affecting their safety and efficacy. Summary of the Invention

[0008] To address the above problems, this invention provides a method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions, the operation steps of which are as follows:

[0009] Preparation of S1 antibacterial masterbatch: 1-5 parts of composite complexed nano-silver 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 mixed evenly; the nano-silver antibacterial masterbatch is obtained by fully mixing and extruding granulation using a twin-screw extruder.

[0010] Preparation of S2 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 silica (an anti-blocking agent with a particle size of 10-20 micrometers) 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 micrometers. 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: A dry lamination process is used to laminate an extruded moisture-proof and antibacterial film layer with an aluminum foil 10-15 micrometers thick. First, a polyurethane adhesive is evenly coated onto the surface of the moisture-proof and antibacterial film layer, with a coating amount of 3-5 grams per square meter. Then, the aluminum foil and the adhesive-coated film layer are laminated on a laminating machine at a lamination temperature of 60-70℃ and a lamination pressure of 0.3-0.5 MPa. After lamination, the material is cured at 40-50℃ for 24-48 hours to fully cure the adhesive and ensure a strong bond between the aluminum foil and the moisture-proof and antibacterial film layer.

[0012] Preparation of the S4 outer protective layer: A biaxially oriented polypropylene film with a thickness of 20-30 micrometers is selected as the outer protective layer; a dry lamination process is used to coat a thin layer of polyurethane adhesive on the surface of the laminated aluminum foil-moisture-proof and antibacterial film layer, with a coating amount of 2-3 grams per square meter; then it is laminated with the biaxially oriented polypropylene film at a lamination temperature of 50-60℃ and a lamination pressure of 0.2-0.4 MPa; after lamination, it is cured at 35-45℃ 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 temperature of the feeding section of the twin-screw extruder is 160-170℃, the temperature of the compression section is 170-180℃, the temperature of the metering section is 180-190℃, the temperature of the die head is 190-200℃, 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℃, the temperature of the plasticizing section is 160-170℃, the temperature of the homogenizing section is 170-180℃, and the temperature of the die head is 180-190℃.

[0016] As a preferred embodiment of the present invention, the method for preparing the composite complexed silver nanoparticles is as follows:

[0017] A1 Mixed Reactants: In a clean glass reaction vessel, measure out the corresponding solutions according to the mass ratio of nano-silver-mercaptoacetic acid coordination complex: polyoxyethylene diamine: fig protease: citrate buffer of 0.5:1-2:1:0.004-0.05:100-120 and add them to the vessel.

[0018] A2 undergoes acylation reaction: The reaction vessel is placed in a constant temperature shaker and stirred continuously at 100-300 rpm for 4-8 hours at a temperature of 30-37℃.

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

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

[0021] H1: Add the nano-silver particles to a clean glass reaction vessel at a molar ratio of 1:5 to 1:20 for mercaptoacetic acid; place the reaction vessel on a magnetic stirrer and stir continuously at a stirring speed of 200-500 rpm for 1-3 hours at room temperature of 20-25℃ to allow the two to fully complex and react.

[0022] 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 5000-10000 rpm for 10-30 minutes. The precipitate is washed 2-3 times with deionized water to obtain the nano silver-mercaptoacetic acid coordination complex.

[0023] Reaction mechanism

[0024] Formation of the nano-silver-mercaptoacetic acid coordination complex: In the mercaptoacetic 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 nano-silver particles have empty orbitals. According to the principles of coordination chemistry, the lone pair of electrons from the sulfur atom fills the empty orbitals of the silver atom, forming a coordinate bond. This coordination interaction allows mercaptoacetic acid to bind tightly to the surface of the nano-silver particles, forming the nano-silver-mercaptoacetic acid coordination complex.

[0025] Formation of the complex silver nanoparticles: Under the stable acid-base environment provided by citrate buffer, the carboxyl group (-COOH) in the silver nanoparticle-mercaptoacetic acid coordination complex exhibits a certain degree of electrophilicity. The amino groups (-NH2) at both ends of the polyoxyethylene diamine molecule are nucleophiles. The nitrogen atom on the amino group carries a lone pair of electrons, which will attack the carbonyl carbon atom in the carboxyl group, resulting in a nucleophilic addition-elimination reaction, i.e., an acylation reaction, to form an amide bond (-CONH-).

[0026] Meanwhile, the active groups (such as amino and carboxyl groups) on the fig protease molecule also participate in similar acylation reactions, thereby linking polyoxyethylene diamine and fig protease to the nano-silver-thioglycolic acid coordination complex to form a complex nano-silver.

[0027] Technical effect

[0028] The present invention discloses 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 advantages:

[0029] 1. Prevention of Agglomeration: The complexation of mercaptoacetic acid with silver nanoparticles, and the subsequent linkage of polyoxyethylene diamine and fig protease, creates a multi-layered structure on the surface of the silver nanoparticles. Mercaptoacetic acid first forms a coating on the surface of the silver nanoparticles, increasing the steric hindrance between particles and preventing direct contact between them. The subsequent linkage of polyoxyethylene diamine and fig protease further increases the steric hindrance, and these molecules are hydrophilic, forming a hydration layer around the silver nanoparticles, effectively preventing aggregation and ensuring stable dispersion in the solution.

[0030] 2. Multifunctionality: Polyoxyethylene diamine increases the hydrophilicity and modifiability of the complex. The hydrophilicity enables the composite complexed silver nanoparticles to exhibit good dispersibility and compatibility in vivo or in aqueous solutions, which is beneficial for their application in the biomedical field.

[0031] 3. Enhanced Barrier Performance: The formation of the nano-silver-thioglycolic acid coordination complex has a positive impact on the barrier performance of the subsequently prepared packaging materials. On one hand, the coating layer formed by thioglycolic acid on the surface of nano-silver alters the surface properties of the nano-silver particles, improving their compatibility with the packaging material matrix (such as polyethylene) and resulting in more uniform dispersion within the matrix. The uniformly dispersed nano-silver 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 nano-silver particles, thereby increasing their diffusion path length, effectively reducing the permeability of gases and moisture, and improving the barrier performance of the packaging material. Detailed Implementation

[0032] To further illustrate the technical means and effects of the present invention in achieving the intended purpose, the following detailed description of the specific implementation methods, structures, features and effects of the present invention, in conjunction with preferred embodiments, is provided below.

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

[0034] 2. Moisture-proof performance test: Using the moisture permeation cup method, the composite material is sealed on the moisture permeation cup, the cup is filled with desiccant, and placed in an environment with a temperature of 38℃ and a relative humidity of 90%. The weight change of the moisture permeation cup is measured over a certain period of time, and the water vapor transmission rate is calculated.

[0035] 3. Barrier performance testing: The oxygen barrier performance of the composite material was tested using a differential pressure gas permeation analyzer.

[0036] 4. Mechanical property testing: The tensile strength of the composite material is tested using a universal testing machine.

[0037] Example 1

[0038] A method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions, comprising the following steps:

[0039] Preparation of S1 antibacterial masterbatch: 1g of composite complexed nano-silver with a particle size of 20 nanometers, 35g of polyethylene, and 0.1g of dispersant zinc stearate were stirred and mixed evenly; the nano-silver antibacterial masterbatch was obtained by fully mixing and extruding granulation using a twin-screw extruder.

[0040] Preparation of S2 moisture-proof and antibacterial film layer: 1g of nano-silver antibacterial masterbatch, 75g of a mixture of linear polyethylene and ethylene-vinyl alcohol copolymer, 0.2g of antioxidant 1010, and 0.3g of silica (an anti-blocking agent with a particle size of 10 micrometers) 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 micrometers. During the extrusion process, a stable screw speed of 150 rpm and a melt pressure of 8 MPa are maintained to ensure uniform film thickness.

[0041] S3 Aluminum Foil Lamination: A dry lamination process is used to laminate an extruded moisture-proof and antibacterial film layer with a 10-micron thick aluminum foil. First, a polyurethane adhesive is evenly coated onto the surface of the moisture-proof and antibacterial film layer at a coating amount of 3 grams per square meter. Then, the aluminum foil and the adhesive-coated film layer are laminated on a laminating machine at a lamination temperature of 60℃ and a lamination pressure of 0.3 MPa. After lamination, the material is cured at 40℃ for 24 hours to fully solidify the adhesive and ensure a strong bond between the aluminum foil and the moisture-proof and antibacterial film layer.

[0042] Preparation of the S4 outer protective layer: A 20-micron thick biaxially oriented polypropylene film was selected as the outer protective layer; a dry lamination process was used to coat a thin layer of polyurethane adhesive on the surface of the laminated aluminum foil-moisture-proof and antibacterial film layer, with a coating amount of 2 g / m²; then it was laminated with the biaxially oriented polypropylene film at a lamination temperature of 50℃ and a lamination pressure of 0.2 MPa; after lamination, it was cured at 35℃ for 12 hours to obtain a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions.

[0043] The twin-screw extruder has a feeding section temperature of 160℃, a compression section temperature of 170℃, a metering section temperature of 180℃, a die head temperature of 190℃, and a screw speed of 200 rpm.

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

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

[0046] The preparation method of the aforementioned composite complexed silver nanoparticles is as follows:

[0047] A1 Mixed Reactants: In a clean glass reaction vessel, measure out the corresponding solutions according to the mass ratio of nano-silver-mercaptoacetic acid coordination complex: polyoxyethylene diamine: fig protease: citrate buffer (CAS No. 13754-17-1) of 0.5:1:1:0.004:100 and add them to the vessel.

[0048] A2 undergoes acylation reaction: The reaction vessel is placed in a constant temperature shaker and stirred continuously at 100 rpm for 4 hours at 30°C.

[0049] A3 Post-processing: After the reaction was completed, an ultrafiltration membrane with a molecular weight cutoff of 10 kDa was selected, and the membrane was centrifuged at 3000 rpm for 10 minutes. The liquid was then removed by distillation to obtain composite complexed silver nanoparticles.

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

[0051] H1: Add the nano-silver particles to a clean glass reaction vessel at a molar ratio of 1:5; place the reaction vessel on a magnetic stirrer and stir continuously at 200 rpm for 1 hour at room temperature of 20°C to allow the two to fully complex and react.

[0052] H2 separation and purification of the complex: After the complexation reaction was completed, the reaction solution was transferred to a centrifuge tube and centrifuged at 5000 rpm for 10 minutes. The precipitate was washed twice with deionized water to obtain the nano-silver-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, comprising the following steps:

[0055] Preparation of S1 antibacterial masterbatch: 2g of composite complexed nano-silver with a particle size of 30 nanometers, 38g of polyethylene, and 0.2g of dispersant zinc stearate were stirred and mixed evenly; the nano-silver antibacterial masterbatch was obtained by fully mixing and extruding granulation using a twin-screw extruder.

[0056] Preparation of S2 moisture-proof and antibacterial film layer: 2g of nano-silver antibacterial masterbatch, 80g of a mixture of linear polyethylene and ethylene-vinyl alcohol copolymer, 0.3g of antioxidant 1010, and 0.4g of silica (15 micrometer particle size) anti-blocking agent 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 micrometers. 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: A dry lamination process is used to laminate an extruded moisture-proof and antibacterial film layer with a 12-micron thick aluminum foil. First, a polyurethane adhesive is evenly coated onto the surface of the moisture-proof and antibacterial film layer at a coating amount of 4 grams per square meter. Then, the aluminum foil and the adhesive-coated film layer are laminated on a laminating machine at a lamination temperature of 65℃ and a lamination pressure of 0.4 MPa. After lamination, the material is cured at 45℃ for 30 hours to fully solidify the adhesive and ensure a strong bond between the aluminum foil and the moisture-proof and antibacterial film layer.

[0058] Preparation of the S4 outer protective layer: A 25-micron thick biaxially oriented polypropylene film was selected as the outer protective layer; a dry lamination process was used to coat a thin layer of polyurethane adhesive on the surface of the laminated aluminum foil-moisture-proof and antibacterial film layer, with a coating amount of 2 g / m²; then it was laminated with the biaxially oriented polypropylene film at a lamination temperature of 55℃ and a lamination pressure of 0.3 MPa; after lamination, it was cured at 8℃ for 18 hours to obtain a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions.

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

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

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

[0062] The preparation method of the aforementioned composite complexed silver nanoparticles is as follows:

[0063] A1 Mixed Reactants: In a clean glass reaction vessel, measure out the corresponding solutions according to the mass ratio of nano-silver-thioglycolic acid coordination complex: polyoxyethylene diamine: fig protease: citrate buffer (CAS No. 13754-17-1) of 0.5:1.3:1:0.02:105 and add them to the vessel.

[0064] A2 undergoes acylation reaction: The reaction vessel is placed in a constant temperature shaker and stirred continuously at 200 rpm for 5 hours at 33°C.

[0065] A3 Post-processing: After the reaction was completed, an ultrafiltration membrane with a molecular weight cutoff of 50 kDa was selected, and the membrane was centrifuged at 4000 rpm for 15 minutes. The liquid was then removed by distillation to obtain composite complexed silver nanoparticles.

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

[0067] H1: Add the nano-silver particles to a clean glass reaction vessel at a molar ratio of 1:10; place the reaction vessel on a magnetic stirrer and stir continuously at 300 rpm for 2 hours at room temperature of 22°C to allow the two to fully complex and react.

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

[0069] Example 3

[0070] A method for preparing a moisture-proof and antibacterial pharmaceutical packaging composite material with multiple barrier functions, comprising the following steps:

[0071] Preparation of S1 antibacterial masterbatch: 4g of composite complexed nano-silver with a particle size of 40 nanometers, 43g of polyethylene, and 0.4g of dispersant zinc stearate were stirred and mixed evenly; the nano-silver antibacterial masterbatch was obtained by fully mixing and extruding granulation using a twin-screw extruder.

[0072] Preparation of S2 moisture-proof and antibacterial film layer: 4g of nano-silver antibacterial masterbatch, 90g of a mixture of linear polyethylene and ethylene-vinyl alcohol copolymer, 0.4g of antioxidant 1010, and 0.5g of silica (15 micrometer particle size) anti-blocking agent 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 micrometers. 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: A dry lamination process is used to laminate an extruded moisture-proof and antibacterial film layer with a 14-micron thick aluminum foil. First, a polyurethane adhesive is uniformly coated on the surface of the moisture-proof and antibacterial film layer at a coating amount of 4 grams per square meter. Then, the aluminum foil and the adhesive-coated film layer are laminated on a laminating machine at a lamination temperature of 65°C and a lamination pressure of 0.4 MPa. After lamination, the material is cured at 45°C for 45 hours to fully cure the adhesive and ensure a strong bond between the aluminum foil and the moisture-proof and antibacterial film layer.

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

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

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

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

[0078] The preparation method of the aforementioned composite complexed silver nanoparticles is as follows:

[0079] A1 Mixed Reactants: In a clean glass reaction vessel, measure out the corresponding solutions according to the mass ratio of nano-silver-mercaptoacetic acid coordination complex: polyoxyethylene diamine: fig protease: citrate buffer (CAS No. 13754-17-1) of 0.5:1.8:1:0.04:115 and add them to the vessel.

[0080] A2 undergoes acylation reaction: The reaction vessel is placed in a constant temperature shaker and stirred continuously at 200 rpm for 7 hours at 36°C.

[0081] A3 Post-processing: After the reaction was completed, an ultrafiltration membrane with a molecular weight cutoff of 80 kDa was selected, and the membrane was centrifuged at 4000 rpm for 25 minutes. The liquid was then removed by distillation to obtain composite complexed silver nanoparticles.

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

[0083] H1: Add the nano-silver particles to a clean glass reaction vessel at a molar ratio of 1:15; place the reaction vessel on a magnetic stirrer and stir continuously at 400 rpm for 2 hours at room temperature of 24°C to allow the two to fully complex and react.

[0084] H2 separation and purification of the complex: After the complexation reaction was completed, the reaction solution was transferred to a centrifuge tube and centrifuged at 8000 rpm for 25 minutes. The precipitate was washed three times with deionized water to obtain the nano-silver-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, comprising the following steps:

[0087] Preparation of S1 antibacterial masterbatch: 5g of composite complexed nano-silver with a particle size of 50 nanometers, 45g of polyethylene, and 0.5g of dispersant zinc stearate were stirred and mixed evenly; the nano-silver antibacterial masterbatch was obtained by fully mixing and extruding granulation using a twin-screw extruder.

[0088] Preparation of S2 moisture-proof and antibacterial film layer: 5g of nano-silver antibacterial masterbatch, 95g of a mixture of linear polyethylene and ethylene-vinyl alcohol copolymer, 0.5g of antioxidant 1010, and 0.6g of silica (particle size 20 micrometers) as an anti-blocking agent 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 micrometers. 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: A dry lamination process is used to laminate an extruded moisture-proof and antibacterial film layer with a 15-micron thick aluminum foil. First, a polyurethane adhesive is uniformly coated on the surface of the moisture-proof and antibacterial film layer at a coating amount of 5 grams per square meter. Then, the aluminum foil and the adhesive-coated film layer are laminated on a laminating machine at a lamination temperature of 70°C and a lamination pressure of 0.5 MPa. After lamination, the material is cured at 50°C for 48 hours to fully cure the adhesive and ensure a strong bond between the aluminum foil and the moisture-proof and antibacterial film layer.

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

[0091] The twin-screw extruder has a feeding section temperature of 170℃, a compression section temperature of 180℃, a metering section temperature of 190℃, a die head temperature of 200℃, and a screw speed of 300 rpm.

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

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

[0094] The preparation method of the aforementioned composite complexed silver nanoparticles is as follows:

[0095] A1 Mixed Reactants: In a clean glass reaction vessel, measure out the corresponding solutions according to the mass ratio of nano-silver-thioglycolic acid coordination complex: polyoxyethylene diamine: fig protease: citrate buffer (CAS No. 13754-17-1) of 0.5:2:1:0.05:120 and add them to the vessel.

[0096] A2 undergoes acylation reaction: The reaction vessel is placed in a constant temperature shaker and stirred continuously at 300 rpm for 8 hours at 37°C.

[0097] A3 Post-processing: After the reaction was completed, an ultrafiltration membrane with a molecular weight cutoff of 100 kDa was selected, and the membrane was centrifuged at 5000 rpm for 30 minutes. The liquid was then removed by distillation to obtain composite complexed silver nanoparticles.

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

[0099] H1: Add the nano-silver particles to a clean glass reaction vessel at a molar ratio of 1:20; place the reaction vessel on a magnetic stirrer and stir continuously at 500 rpm for 3 hours at room temperature of 25°C to allow the two to fully complex and react.

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

[0101] Comparative Example 1

[0102] Without adding composite complexed silver nanoparticles, or with adding silver nanoparticles, the rest is the same as in Example 1.

[0103] Comparative Example 2

[0104] Without adding the nano-silver-mercaptoacetic acid coordination complex, everything else is the same as in Example 1.

[0105] Comparative Example 3

[0106] Polyoxyethylene diamine was not added; otherwise, it was the same as in Example 1.

[0107] Table 1: Test Data Results of Examples and Comparative Examples

[0108]

[0109]

[0110] Based on the data analysis of the above embodiments 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 is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A method for preparing a moisture-proof and antibacterial medical packaging composite material with multiple barrier functions, comprising the following steps: S1: preparing an antibacterial master batch by mixing 1-5 parts of complexed nano-silver with a particle size of 20-50 nm, 35-45 parts of polyethylene, and 0.1-0.5 parts of a dispersing agent zinc stearate; S2: preparing a moisture-proof and antibacterial film layer by mixing 1-5 parts of the nano-silver antibacterial master batch, 75-95 parts of a mixture of linear polyethylene and ethylene-vinyl alcohol copolymer, 0.2-0.5 parts of an antioxidant 1010, and 0.3-0.6 parts of an anti-blocking agent silicon dioxide with a particle size of 10-20 microns in a single screw extruder and extruding through a T-shaped die to form a moisture-proof and antibacterial film layer with a thickness of 30-40 microns; S3: aluminum foil compounding by using a dry compounding process to compound the extruded moisture-proof and antibacterial film layer with an aluminum foil with a thickness of 10-15 microns; first, uniformly coating a polyurethane adhesive on the surface of the moisture-proof and antibacterial film layer at a coating amount of 3-5 g / m2; then, compounding the aluminum foil and the film layer coated with the adhesive on a compounding machine at a compounding temperature of 60-70 DEG C and a compounding pressure of 0.3-0.5 MPa; after compounding, curing the material at an environment of 40-50 DEG C for 24-48 hours to fully solidify the adhesive and ensure the firm combination of the aluminum foil and the moisture-proof and antibacterial film layer; S4: preparing an outer protective layer by selecting a biaxially stretched polypropylene film with a thickness of 20-30 microns as the outer protective layer; using a dry compounding process to coat a thin layer of polyurethane adhesive on the surface of the compounded aluminum foil-moisture-proof and antibacterial film layer at a coating amount of 2-3 g / m2; then, compounding the biaxially stretched polypropylene film at a compounding temperature of 50-60 DEG C and a compounding pressure of 0.2-0.4 MPa; after compounding, curing at an environment of 35-45 DEG C for 12-24 hours to obtain a moisture-proof and antibacterial medical packaging composite material with multiple barrier functions. The complexed nano-silver is prepared by a reaction of nano-silver-mercaptoacetic acid coordination complex, polyoxyethylene diamine, ficin, and citrate buffer. The temperature of the feeding section of the double screw extruder is 160-170 DEG C, the temperature of the compression section is 170-180 DEG C, the temperature of the metering section is 180-190 DEG C, the temperature of the head is 190-200 DEG C, and the screw rotation speed is 200-300 rpm. The mixture of linear polyethylene and ethylene-vinyl alcohol copolymer has a mass ratio of 5-7:

3. The temperature of the feeding section of the single screw extruder is 150-160 DEG C, the temperature of the plasticizing section is 160-170 DEG C, the temperature of the homogenizing section is 170-180 DEG C, and the temperature of the die is 180-190 DEG C. The preparation method of the complexed nano-silver is:

2. The method for preparing a moisture-proof and antibacterial medical packaging composite material with multiple barrier functions according to claim 1, characterized in that: ​ 3. The method for preparing the moisture-proof and antibacterial medical packaging composite material with multiple barrier functions according to claim 1, characterized in that: ​ 4. The method for preparing the moisture-proof and antibacterial medical packaging composite material with multiple barrier functions according to claim 1, characterized in that: ​ 5. The method for preparing the moisture-proof and antibacterial medical packaging composite material with multiple barrier functions according to claim 1, characterized in that: ​ A1 mixing reactants: in a clean glass reaction vessel, according to the mass ratio of nano-silver-mercapto acetic acid coordination complex: polyoxyethylene diamine: ficin: citrate buffer is 0.5:1-2:1:0.004-0.05:100-120, the corresponding solution is added to the container respectively; A2 acylation reaction: the reaction vessel is placed in a constant temperature shaker, and the reaction is continuously stirred at a speed of 100-300 rpm for 4-8 hours at a temperature of 30-37℃; A3 post-processing: after the reaction is completed, an ultrafiltration membrane with a molecular weight cut-off of 10-100 kDa is selected, and centrifugal ultrafiltration is performed at a speed of 3000-5000 rpm for 10-30 minutes, and the liquid is removed by distillation to obtain the complex coordination nano-silver.

6. The method for preparing a moisture-proof and antibacterial medical packaging composite material with multiple barrier functions according to claim 5, characterized in that: The preparation method of the nano-silver-mercapto acetic acid coordination complex is: H1: according to the molar ratio of nano-silver particles to mercapto acetic acid is 1:5-1:20, add clean glass reaction container; the reaction vessel is placed on a magnetic stirrer, and continuously stirred at a speed of 200-500 rpm for 1-3 hours at room temperature of 20-25℃, so that the two are fully complexed; H2 separation and purification of complex: after the complexation reaction is completed, the reaction liquid is transferred to a centrifuge tube, centrifuged at a speed of 5000-10000 rpm for 10-30 minutes, and the precipitate is washed with deionized water for 2-3 times to obtain the nano-silver-mercapto acetic acid coordination complex.

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