Medical packaging composite film and preparation method thereof

Abstract

The invention provides a medical packaging composite film and a preparation method thereof. The preparation method of the medical composite membrane comprises the following steps: S100, coating a first surface of an aluminum foil layer with an adhesive, attaching the first surface to a barrier material, and sequentially carrying out primary drying treatment and calendering treatment to obtain a barrier layer, an adhesive layer and the aluminum foil layer; s200, the second surface of the aluminum foil layer is coated with heat sealing slurry, secondary drying treatment is conducted, and the medical packaging composite film is obtained. The medical packaging composite film has excellent barrier property, biological safety, mechanical property and heat sealing property, and can provide reliable packaging protection for medical drugs.

Description

Technical Field

[0001] The invention relates to the field of medical film packaging, and in particular to a medical packaging composite film and a preparation method thereof. Background Art

[0002] Packaging film is widely used in all walks of life and is suitable for packaging goods of various shapes. Sealed and packaged goods are hygienic, clean, dustproof and moisture-proof, and can also give products good protection. The barrier performance of packaging film is an important indicator to measure the quality of packaging film, and it will also directly affect the packaging effect of the product. When using packaging film to package products, most of the changes in its contents are due to the poor barrier properties of the packaging film, which is affected by moisture, oxygen, and microorganisms. In order to improve the sealing of packaging, aluminum foil and aluminum-plastic composite materials are widely used as barrier functional packaging materials in the packaging field.

[0003] Medical packaging requires that the packaging film has good retort and corrosion resistance. Therefore, how to obtain a packaging film that is both retort and corrosion resistant is an issue that the medical packaging industry must consider. Summary of the invention

[0004] Therefore, the present invention provides a medical packaging composite film and a preparation method thereof, so that the medical packaging composite film has excellent barrier properties, biosafety, mechanical properties and heat sealing properties, and can provide reliable packaging protection for medical drugs.

[0005] The invention provides a method for preparing a medical packaging composite film, which comprises the following steps: S100: coating an adhesive on a first surface of an aluminum foil layer, laminating the adhesive with a barrier material, and sequentially performing a drying process and a calendering process to obtain a barrier layer, an adhesive layer, and an aluminum foil layer; S200: coating a heat-sealing slurry on a second surface of the aluminum foil layer and performing a secondary drying process to obtain a medical packaging composite film; wherein the method for preparing the barrier material comprises the following steps: S110: mixing chitosan, alanine, potassium sorbate, wheat germ, and succinic acid with deionized water; The maltitol is fully dissolved to obtain a pretreatment solution; S120: Poloxamer 188 is further fully dissolved in the pretreatment solution to obtain a barrier material; the adhesive includes: a polyurethane adhesive or an acrylate adhesive; the heat sealing slurry includes the following raw material content components by weight: 20-35 parts of modified heat-resistant particles, 0.01-1 parts of a dispersant, 1-5 parts of an adhesive, 0.1-3 parts of a thickener and 50-75 parts of water; the modified heat-resistant particles are obtained by modifying the modified heat-resistant particles with a modifier; the modifier includes polyetheretherketone and polyimide.

[0006] Compared with the prior art, the technical effect achieved by adopting the technical scheme is as follows: the preparation method of the barrier material of the present application firstly uses deionized water to fully dissolve chitosan, alanine, potassium sorbate and maltitol to obtain a pretreatment solution, wherein chitosan as a natural polymer material has good biocompatibility and antibacterial properties, and can improve the biosafety of the composite film; alanine as an amino acid can enhance the toughness and softness of the material and increase the biocompatibility of the material; potassium sorbate as a preservative can effectively inhibit the growth of microorganisms and extend the service life of the composite film; maltitol as a humectant can maintain the humidity of the composite film to prevent drying and cracking; finally, poloxamer 188 is fully dissolved in the pretreatment solution to obtain a barrier material, and poloxamer 188 as a surfactant can improve the uniformity and stability of the solution and improve the processing performance of the material; the adhesive is used to firmly bond the materials of different layers together to ensure the integrity and strength of the composite film;

[0007] The modified heat-resistant particles in the heat-sealing slurry of the present application can provide heat-sealing properties for the composite film, ensuring that the material will not melt or deform during the heat-sealing process; the modifiers of the modified heat-resistant particles include polyetheretherketone and polyimide, which have excellent heat resistance and mechanical strength; the dispersant helps the modified heat-resistant particles to be evenly dispersed in water to prevent particle agglomeration; the adhesive further enhances the bonding properties of the heat-sealing layer with other layers; the thickener adjusts the viscosity of the slurry to make it easier to coat on the aluminum foil layer; water is used as a solvent to help mix the other ingredients into a uniform slurry.

[0008] Therefore, the medical packaging composite film of the present application can effectively block water vapor, oxygen, etc., protect the internal medicines from the influence of the external environment, and extend the shelf life of the medicines; and because the natural ingredients such as chitosan and alanine in the composite film have good biocompatibility and antibacterial properties, the safety of the medicines is guaranteed; on the one hand, through reasonable material combination and processing technology, the composite film has good toughness, strength and heat resistance, and can adapt to various packaging and storage conditions; on the other hand, the excellent heat sealing performance provided by the modified heat-resistant particles ensures that the packaging will not be deformed or damaged during the heat sealing process, thereby ensuring the sealing effect; in summary, the medical packaging composite film of the present application has excellent barrier properties, biosafety, mechanical properties and heat sealing properties, and can provide reliable packaging protection for medical drugs.

[0009] In one technical solution of the present invention, the following raw material components are included in S110 by weight: 0.1-5 parts of chitosan, 0.01-1 parts of alanine, 0.1-0.2 parts of potassium sorbate, 0.1-1 parts of maltitol and 0.01-1 parts of poloxamer 188.

[0010] Compared with the prior art, the technical effects achieved by adopting this technical scheme are as follows: in step S110, the chitosan in the barrier material is a natural polymer material with good biocompatibility and antibacterial properties, which can form a film with good barrier properties, prevent the penetration of moisture and oxygen, and protect the stability of the internal drugs; alanine is a natural amino acid with good biocompatibility, which can enhance the flexibility and mechanical strength of the material and improve the physical properties of the composite film; potassium sorbate is a medical preservative, which is safe and non-toxic, and can effectively inhibit the growth of bacteria and mold, extend the service life of the composite film and maintain the safety of drugs; maltitol is a humectant with low hygroscopicity and high stability, which can maintain the wettability of the composite film, prevent drying and cracking, and ensure the integrity of the film; poloxamer is a non-ionic surfactant with good solubility and stability, which can improve the uniformity of the solution, help other components to be evenly dispersed, and improve the processing performance of the material and the quality of the composite film. Therefore, the combination of the above components can provide a medical composite film with high barrier properties, good mechanical properties and biocompatibility, ensuring the reliability of medical packaging and the safety of drugs, enabling it to effectively block moisture and oxygen in the environment, inhibit the growth of microorganisms, while maintaining the flexibility and stability of the film.

[0011] In one technical solution of the present invention, the following raw material components are included in S110 by weight: 2 parts of chitosan, 0.5 parts of alanine, 0.15 parts of potassium sorbate, 0.5 parts of maltitol and 0.5 parts of poloxamer 188.

[0012] Compared with the existing technology, the technical effect achieved by adopting this technical solution is as follows: through appropriate ratios, a medical packaging composite film with excellent performance can be provided, so that the components in the medical packaging composite film cooperate with each other to achieve an optimal mass ratio, thereby effectively protecting the stability and safety of the internal drugs.

[0013] In one technical solution of the present invention, a method for preparing a heat-sealing slurry comprises the following steps: A. mixing a thickener and water to obtain a thickener solution, and mixing a dispersant and water to obtain a first premixed liquid; B. mixing the first premixed liquid and the thickener solution to obtain a second premixed liquid; C. adding modified heat-resistant particles to the second premixed liquid to obtain a third premixed liquid; D. mixing the third premixed liquid with an adhesive to prepare a heat-sealing slurry.

[0014] Compared with the existing technology, the technical effects achieved by adopting this technical scheme are as follows: each step of the mixing and dispersing process is finely controlled to ensure the uniformity and stability of the slurry; the modified heat-resistant particles provide good heat resistance to ensure that the slurry will not deform or melt during the heat sealing process; the reasonable ratio of the thickener and the adhesive gives the slurry sufficient mechanical strength to ensure the heat sealing effect; the addition of the adhesive improves the adhesion properties of the slurry to ensure the sealing effect of the medical composite film.

[0015] In one technical scheme of the present invention, the preparation method of modified heat-resistant particles includes: mixing heat-resistant particles, water and a modifier, conducting a hydrothermal reaction at 160°C-200°C for 2h-8h, then cooling and solid-liquid separation, and drying the obtained solid material to obtain modified heat-resistant particles.

[0016] Compared with the prior art, the technical effect achieved by adopting this technical solution is as follows: heat-resistant particles, water and modifiers are mixed, and the modifiers are evenly distributed on the surface of the heat-resistant particles to promote full contact between the modifiers and the heat-resistant particles, thereby improving the modification efficiency; subsequently, a hydrothermal reaction is carried out at 160°C-200°C for 2h-8h. The high-temperature and high-pressure hydrothermal reaction is helpful for chemical bonding between the modifier and the heat-resistant particles, thereby improving the heat resistance and stability of the particles. The modifier can effectively penetrate and adhere to the surface of the heat-resistant particles, thereby making the modified heat-resistant particles have better heat resistance and mechanical strength, and can remain stable in a high temperature environment without deformation. The particles are then cooled and solid-liquid separated to effectively prevent internal stress and cracks caused by rapid cooling, and unreacted modifiers and other by-products are removed to obtain pure modified heat-resistant particles, thereby ensuring the structural integrity and purity of the particles, and obtaining a uniform and pure solid material; thereby making the modified heat-resistant particles stable at high temperatures, free from deformation and degradation, and suitable for heat-sealing slurries that require high-temperature processing, and having higher strength and toughness, and being able to remain stable in various applications. In addition, the purity and uniformity of the particles are ensured to ensure consistency in performance, and the dried particles are not prone to moisture absorption and deterioration, and are suitable for long-term storage and use.

[0017] In one technical solution of the present invention, the modified heat-resistant particles include at least one of aluminum oxide, zirconium oxide, and silicon dioxide; and / or the particle size of the modified heat-resistant particles is 0.2 μm-2.0 μm; and / or the thickener is a carboxymethyl cellulose thickener; and / or the dispersant is an aqueous polymer dispersant.

[0018] Compared with the existing technology, the technical effects achieved by adopting this technical solution are as follows: the modified heat-resistant particles can remain stable in a high temperature environment, improving the heat sealing performance and mechanical strength of the composite film; the reasonable particle size and high-quality dispersant ensure the uniform distribution of the particles in the slurry, prevent agglomeration, and improve the stability of the slurry; the use of carboxymethyl cellulose thickeners and aqueous dispersants ensures that the materials are environmentally friendly and non-toxic, and meet the safety requirements of medical packaging; by selecting suitable heat-resistant particles, the barrier properties of the composite film can be improved, and the stability and safety of the internal drugs can be protected; the above components can significantly improve the overall performance of the medical packaging composite film, ensuring the safety and stability of the drugs during storage and use.

[0019] In one technical solution of the present invention, in S100, the temperature of the primary drying treatment is 60-100°C; and / or in S100, the temperature of the calendering treatment is 50-150°C; and / or in S100, the pressure of the calendering treatment is 10-100MPa; and / or in S200, the temperature of the secondary drying treatment is 60-100°C.

[0020] Compared with the existing technology, the technical effect achieved by adopting this technical solution is as follows: through the above-mentioned appropriate process parameters, the composite film exhibits excellent barrier properties, mechanical properties and heat sealing properties in actual use, and the medical packaging composite film can meet the expected performance requirements, ensuring its reliability and durability in various application environments.

[0021] In one technical solution of the present invention, the aluminum foil layer includes aluminum, iron and nickel; wherein the mass ratio of aluminum, iron and nickel is (97.8-98.2):(0.4-0.6):(0.4-0.6).

[0022] Compared with the existing technology, the technical effects achieved by adopting this technical solution are as follows: aluminum as the main component in the aluminum foil layer provides excellent barrier properties, effectively blocks the penetration of oxygen, water vapor and other gases, and protects the items in the package; an appropriate amount of iron and nickel can enhance the mechanical strength of the aluminum foil, making it more resistant to external physical damage, and can improve the stability and heat resistance of the aluminum foil layer, so that it maintains its performance under high temperature or other harsh environments; in addition, nickel is an effective anti-corrosion material that can increase the corrosion resistance of the aluminum foil layer and extend its service life; this ratio of aluminum foil layer not only meets the requirements of medical packaging, but can also be used in more scenarios that require high strength, corrosion resistance and high temperature stability, and has wide applicability and excellent comprehensive performance.

[0023] In one technical solution of the present invention, the thickness of the barrier layer is 5 μm to 25 μm; and / or the thickness of the adhesive layer is 1 μm to 10 μm; and / or the thickness of the aluminum foil layer is 5 μm to 20 μm; and / or the thickness of the heat sealing layer is 20 μm to 50 μm.

[0024] Compared with the prior art, the technical effects achieved by adopting this technical solution are as follows: the thickness of the barrier layer is between 5μm and 25μm, and the thickness of the barrier layer directly affects its barrier ability to gas, moisture and light. The appropriate thickness improves the mechanical strength, stability and consistency of the barrier layer, and avoids damage or failure during processing and use; the thickness of the adhesive layer is between 1μm and 10μm, and the thickness of the adhesive layer determines its adhesion to other layers. The appropriate thickness can avoid deformation or failure of the adhesive layer under high temperature or pressure, and prevent the adhesive layer from falling off or Failure ensures the integrity of the package; the thickness of the aluminum foil layer is between 5μm and 20μm, and the thickness of the aluminum foil layer determines its ability to resist stretching and tearing. The aluminum foil layer can provide excellent barrier properties to protect internal items from the influence of the external environment; the thickness of the heat sealing layer is between 20μm and 50μm, and the thickness of the heat sealing layer affects the sealing effect formed during the heat sealing process. The heat sealing layer can provide effective sealing during the heat sealing process to ensure the safety and stability of the package. The increase in thickness makes the heat sealing layer have better durability and damage resistance, and is suitable for various harsh use environments.

[0025] Compared with the existing technology, the technical effect achieved by adopting this technical solution is: it does not rely on a large number of trial and error adjustments, and the number of trials can be reduced through intelligent algorithms. During the optimization process, the algorithm can continuously approach the optimal process conditions through iteration and learning, thereby greatly reducing the cost and time of experiments. The intelligent control algorithm can monitor and adjust the key parameters of the production process in real time to ensure the consistency of product quality.

[0026] A medical packaging composite film is prepared by the above-mentioned preparation method, and thus includes the beneficial effects possessed by any of the above-mentioned technical solutions, which will not be described in detail here.

[0027] After adopting the technical solution of the present invention, the following technical effects can be achieved:

[0028] (1) The medical packaging composite film of the present application can effectively block water vapor, oxygen, etc., protect the internal drugs from the influence of the external environment, and extend the shelf life of the drugs; and because the natural ingredients such as chitosan and alanine in the composite film have good biocompatibility and antibacterial properties, the safety of the drugs is guaranteed; on the one hand, through reasonable material combination and processing technology, the composite film has good toughness, strength and heat resistance, and can adapt to various packaging and storage conditions; on the other hand, the excellent heat sealing performance provided by the modified heat-resistant particles ensures that the packaging will not be deformed or damaged during the heat sealing process, ensuring the sealing effect; in summary, the medical packaging composite film of the present application has excellent barrier properties, biosafety, mechanical properties and heat sealing properties, and can provide reliable packaging protection for medical drugs;

[0029] (2) The modified heat-resistant particles can remain stable in high temperature environments, improve the heat sealing properties and mechanical strength of the composite film, and the reasonable particle size and high-quality dispersant ensure the uniform distribution of the particles in the slurry, prevent agglomeration, and improve the stability of the slurry. The use of carboxymethyl cellulose thickeners and aqueous dispersants ensures that the materials are environmentally friendly and non-toxic, and meet the safety requirements of medical packaging. By selecting suitable heat-resistant particles, the barrier properties of the composite film can be improved, and the stability and safety of the internal drugs can be protected. The above components can significantly improve the overall performance of the medical packaging composite film, ensuring the safety and stability of the drugs during storage and use.

[0030] (3) Intelligent control algorithms can quickly and efficiently explore the optimal combination of raw material ratios and process parameters by simulating mechanisms such as natural selection and genetic variation. This optimization process can significantly improve the barrier properties, biosafety and heat resistance of materials while controlling costs. Traditional material research and development usually relies on a large number of trial and error adjustments, and intelligent algorithms can reduce the number of trials. During the optimization process, the algorithm can continuously approach the optimal process conditions through iteration and learning, thereby significantly reducing experimental costs and time. Intelligent control algorithms can monitor and adjust key parameters in the production process in real time to ensure the consistency of product quality. Through intelligent control of parameters such as temperature, pressure, and viscosity, the volatility of the production process can be effectively controlled, thereby improving the qualified rate of the final product. Intelligent control algorithms can dynamically adjust production parameters based on real-time feedback, making the system more sensitive and adaptable to external changes. Intelligent control algorithms optimize in a systematic and data-driven manner, making every step of the R&D and production process traceable and repeatable. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 It is a flow chart of the intelligent control algorithm in the present invention. DETAILED DESCRIPTION

[0032] In order to make the above-mentioned purposes, features and advantages of the present invention more obvious and understandable, the technical solutions in the embodiments of the present invention are described clearly and completely. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0033] Medical packaging requires that the packaging film has good retort and corrosion resistance. Therefore, how to obtain a packaging film that is both retort and corrosion resistant is an issue that the medical packaging industry must consider.

[0034] The present invention provides a method for preparing a medical packaging composite film, the preparation method comprising the following steps:

[0035] S100: coating an adhesive on the first surface of the aluminum foil layer, laminating it with a barrier material, and sequentially performing a drying process and a calendering process to obtain a barrier layer, an adhesive layer, and an aluminum foil layer;

[0036] The preparation method of the barrier material comprises the following steps:

[0037] S110: fully dissolving chitosan, alanine, potassium sorbate, and maltitol with deionized water to obtain a pretreatment solution;

[0038] Furthermore, the following raw material components are included by weight: 0.1-5 parts of chitosan, 0.01-1 parts of alanine, 0.1-0.2 parts of potassium sorbate, 0.1-1 parts of maltitol and 0.01-1 parts of poloxamer 188.

[0039] Preferably, chitosan is a natural polymer material with good biocompatibility and antibacterial properties, and can form a film with good barrier properties to prevent the penetration of moisture and oxygen and protect the stability of the internal medicine; alanine is a natural amino acid with good biocompatibility, and can enhance the flexibility and mechanical strength of the material and improve the physical properties of the composite film; potassium sorbate is a medical preservative, which is safe and non-toxic, and can effectively inhibit the growth of bacteria and mold, prolong the service life of the composite film and maintain the safety of the medicine; maltitol is a humectant with low hygroscopicity and high stability, which can maintain the wettability of the composite film, prevent drying and cracking, and ensure the integrity of the film;

[0040] S120: fully dissolving poloxamer 188 in the pretreatment solution to obtain a barrier material;

[0041] Preferably, poloxamer is a nonionic surfactant with good solubility and stability, which can improve the uniformity of the solution, help other components to be evenly dispersed, and improve the processing performance of the material and the quality of the composite film. Thus, the combination of the above components can provide a medical composite film with high barrier properties, good mechanical properties and biocompatibility, ensure the reliability of medical packaging and the safety of drugs, enable it to effectively block moisture and oxygen in the environment, inhibit the growth of microorganisms, and maintain the flexibility and stability of the film.

[0042] S200: coating a heat-sealing slurry on the second surface of the aluminum foil layer and performing secondary drying to obtain a medical packaging composite film;

[0043] Adhesives include: polyurethane adhesive or acrylate adhesive;

[0044] The heat sealing slurry comprises the following raw material components by weight: 20-35 parts of modified heat-resistant particles, 0.01-1 parts of dispersant, 1-5 parts of adhesive, 0.1-3 parts of thickener and 50-75 parts of water; the modified heat-resistant particles are obtained by modifying the modified heat-resistant particles with a modifier; the modifier includes polyetheretherketone and polyimide.

[0045] Preferably, the modified heat-resistant particles can provide heat-sealing properties for the composite film, ensuring that the material will not melt or deform during the heat-sealing process; the modifiers of the modified heat-resistant particles include polyetheretherketone and polyimide, which have excellent heat resistance and mechanical strength; the dispersant helps the modified heat-resistant particles to be evenly dispersed in water to prevent particle agglomeration; the adhesive further enhances the bonding properties of the heat-sealing layer with other layers; the thickener adjusts the viscosity of the slurry to make it easier to coat on the aluminum foil layer; water acts as a solvent to help mix the other ingredients into a uniform slurry.

[0046] Furthermore, the preparation method of the heat sealing slurry comprises the following steps:

[0047] A. Mix a thickener and water to obtain a thickener solution, and mix a dispersant and water to obtain a first premixed liquid; thereby forming a stable thickener solution, which improves the consistency and stability of the slurry, making the slurry easy to mix and handle in subsequent steps, ensuring the uniformity of the slurry coating during application; mix a dispersant and water, the dispersant can reduce the surface tension between particles, prevent particle agglomeration, and form a stable first premixed liquid. At the same time, the dispersant ensures that the modified heat-resistant particles are evenly dispersed in subsequent steps, improving the uniformity and stability of the slurry.

[0048] B. Mix the first premixed liquid and the thickener solution to obtain a second premixed liquid; combined with the effect of the dispersant, the thickener solution can further stabilize the dispersed particles to form a uniform second premixed liquid, laying the foundation for the subsequent addition of modified heat-resistant particles and adhesives, and ensuring the uniformity of the entire heat-sealing slurry.

[0049] C. Adding modified heat-resistant particles into the second premixed liquid to obtain a third premixed liquid; this can ensure that the particles are evenly dispersed, improve the overall performance of the heat-sealing slurry, and ensure that the heat-sealing slurry has good heat resistance and mechanical strength.

[0050] D. Mixing the third premixed liquid with an adhesive to prepare a heat-sealing slurry can enhance the adhesion and stability of the slurry, so that it can firmly adhere to the aluminum foil layer during the heat-sealing process, so that the final heat-sealing slurry has excellent adhesion, heat resistance and mechanical strength, and can ensure the sealing effect and stability of the packaging material during the heat-sealing process.

[0051] Furthermore, the heat-resistant particles, water and a modifier are mixed, and a hydrothermal reaction is carried out at 160°C-200°C for 2h-8h, followed by cooling and solid-liquid separation, and the obtained solid material is dried to obtain modified heat-resistant particles.

[0052] Preferably, the heat-resistant particles, water and the modifier are mixed, and the modifier is evenly distributed on the surface of the heat-resistant particles to promote full contact between the modifier and the heat-resistant particles, thereby improving the modification efficiency; then a hydrothermal reaction is carried out at 160°C-200°C for 2h-8h. The high temperature and high pressure hydrothermal reaction is conducive to chemical bonding between the modifier and the heat-resistant particles, thereby improving the heat resistance and stability of the particles. The modifier can effectively penetrate and adhere to the surface of the heat-resistant particles, so that the modified heat-resistant particles have better heat resistance and mechanical strength, and can remain stable in a high temperature environment without deformation or degradation; then a cooling Cooling and solid-liquid separation can effectively prevent the particles from generating internal stress and cracks due to rapid cooling, and remove unreacted modifiers and other by-products to obtain pure modified heat-resistant particles, thereby ensuring the structural integrity and purity of the particles, and the obtained solid materials are uniform and pure; thereby making the modified heat-resistant particles stable at high temperatures, without deformation or degradation, and suitable for heat-sealing slurries that require high-temperature processing, and having higher strength and toughness, and being able to remain stable in various applications, and also ensuring the purity and uniformity of the particles, ensuring the consistency of performance, and the dried particles are not easy to absorb moisture and deteriorate, and are suitable for long-term storage and use.

[0053] Furthermore, the modified heat-resistant particles include at least one of aluminum oxide, zirconium oxide, and silicon dioxide, which can improve the heat resistance and mechanical properties of the heat-sealing layer, so that it remains stable in a high-temperature environment, does not deform, and does not degrade, increases the barrier properties of the composite film, prevents the external environment from affecting the internal drugs, extends the shelf life of the drugs, ensures the biosafety of the material, is non-toxic and harmless to the drugs, and is suitable for medical packaging requirements;

[0054] The particle size of the modified heat-resistant particles is 0.2μm-2.0μm. The fine particle size can provide a larger specific surface area and enhance the surface activity of the material. The particle size is within the range of 0.2μm-2.0μm, which can ensure that the particles are evenly dispersed in the slurry to avoid agglomeration.

[0055] The thickener is a carboxymethyl cellulose thickener, which has good thickening effect and water solubility, can significantly increase the viscosity of the slurry, and also has good stability and biodegradability, is environmentally friendly, can increase the consistency of the heat-sealing slurry, make it more uniform and easier to control during the coating process, enhance the stability of the slurry, prevent stratification or precipitation, and increase the service life and reliability of the product. It is environmentally friendly and non-toxic, and meets the safety requirements of medical packaging;

[0056] The dispersant is a water-based polymer dispersant, which can significantly reduce the surface tension of the particles, prevent particle agglomeration, and ensure the uniform dispersion of the particles in the aqueous medium, thereby improving the uniformity and stability of the heat-sealing slurry, ensuring the uniform distribution of the modified heat-resistant particles in the slurry, preventing particle agglomeration, and enhancing the mechanical properties and heat resistance of the heat-sealing layer. In addition, the water-based dispersant is environmentally friendly and non-toxic, and has a positive effect on the safety and environmental protection requirements of medical packaging.

[0057] The modified heat-resistant particles can remain stable in high temperature environments, improve the heat-sealing properties and mechanical strength of the composite film, and the reasonable particle size and high-quality dispersant ensure the uniform distribution of the particles in the slurry, prevent agglomeration, and improve the stability of the slurry; the use of carboxymethyl cellulose thickeners and aqueous dispersants ensures that the materials are environmentally friendly and non-toxic and meet the safety requirements of medical packaging; by selecting suitable heat-resistant particles, the barrier properties of the composite film can be improved to protect the stability and safety of the internal drugs; the above components can significantly improve the overall performance of the medical packaging composite film to ensure the safety and stability of the drugs during storage and use.

[0058] Preferably, the aluminum foil layer includes aluminum, iron, and nickel; wherein the mass ratio of aluminum, iron, and nickel is (97.8-98.2): (0.4-0.6): (0.4-0.6). Aluminum, as the main component in the aluminum foil layer, provides excellent barrier properties, effectively blocks the penetration of oxygen, water vapor, and other gases, and protects the items in the package; an appropriate amount of iron and nickel can enhance the mechanical strength of the aluminum foil, making it more resistant to physical damage from the outside, and can improve the stability and heat resistance of the aluminum foil layer, so that it maintains its performance under high temperature or other harsh environments; in addition, nickel is an effective anti-corrosion material that can increase the corrosion resistance of the aluminum foil layer and extend its service life; this ratio of aluminum foil layer not only meets the requirements of medical packaging, but can also be used in more scenarios that require high strength, corrosion resistance, and high temperature stability, and has a wide range of applicability and excellent comprehensive performance.

[0059] Furthermore, the preparation method of the barrier material and the preparation method of the modified heat-resistant particles are optimized and controlled by an intelligent control algorithm. The specific steps are as follows:

[0060] Step 1: Installation of sensor;

[0061] Component concentration sensor: Install high-precision electrochemical concentration sensors in the chitosan, alanine, potassium sorbate, maltitol, and poloxamer 188 raw material dissolution tanks to monitor the concentration of each raw material in real time to ensure accurate raw material ratios during the mixing process;

[0062] Temperature sensor: High-precision temperature sensors are installed in the dissolving tank, mixing tank and hydrothermal reactor to monitor and control the temperature in each process step to ensure the stability of the dissolving and mixing process;

[0063] Viscosity sensor: A rotational viscometer is installed in the final mixing tank to monitor the viscosity of the mixed barrier material solution to ensure that it meets the process requirements;

[0064] Pressure sensor: Install a piezoelectric pressure sensor in the reactor;

[0065] Particle size sensor: An online detection device equipped with a laser particle size analyzer after the reaction to detect the particle size distribution of the modified heat-resistant particles in real time;

[0066] Step 2: Collection of sensor parameters;

[0067] The concentration of each raw material can be expressed by the following formula:

[0068]

[0069] Among them, C i (t) represents the concentration of the i-th raw material at time t, m i (t) represents the mass of the i-th raw material at time t, and V(t) represents the volume of the solution at time t;

[0070] Temperature control is calculated using the following heat transfer equation:

[0071] Q=mcΔT

[0072] Where Q represents the amount of heat transferred, m represents the mass of the solution, c represents the specific heat capacity of the solution, and ΔT represents the temperature change;

[0073] The calculation formula of dynamic viscosity is:

[0074]

[0075] Where η(t) represents the dynamic viscosity of the fluid at time t, τ represents the shear stress, represents the shear rate;

[0076] Step 3: Preparation and optimization of barrier materials;

[0077] The optimization algorithm GA based on natural selection and genetic mechanism generates different raw material ratio combinations through operations such as selection, crossover, and mutation. The improved sparrow search algorithm ISSA is used to enhance the local search ability of GA to avoid falling into the local optimum. It improves the optimization efficiency by adaptively adjusting the step size and direction.

[0078] Initial population generation:

[0079] X0={x i,0},x i,0 ∈[a i ,b i ]

[0080] Among them, X0 represents the initial population, x i,0 represents the raw material ratio of the i-th individual in its initial state, 0 represents the 0th generation individual of the initial population, and a i Indicates the lower limit of the raw material ratio, b i Indicates the upper limit of the raw material ratio;

[0081] Comprehensive objective function definition:

[0082]

[0083] Among them, F(X) represents the comprehensive objective function, which is used to evaluate the advantages and disadvantages of different material ratios; X represents the material ratio scheme; OTR(X) is the oxygen permeability, which indicates the speed at which the material allows oxygen to pass through; WVTR(X) is the water vapor permeability, which indicates the speed at which the material allows water vapor to pass through. The lower the water vapor permeability, the better the barrier performance of the material; Bio(X) is biosafety, which indicates the compatibility of the material with the biological system. The higher the biosafety, the better; Cost(X) is the material cost, which indicates the cost of manufacturing the material; w1, w2, w3, and w4 are weight coefficients, which are used to adjust the relative importance of each target in the comprehensive objective function;

[0084] In the selection phase, the genetic algorithm determines which individuals will be retained for crossover operations through the selection operator, and the selection probability P i Based on individual fitness F(X i )Sure:

[0085]

[0086] Among them, P i represents the probability of the i-th individual being selected; F(X i ) represents the fitness value of the i-th individual, represents the sum of the fitness values ​​of all individuals, j represents the index of an individual in the current population, and N represents the total number of individuals in the population;

[0087] In the crossover phase, the selected individuals generate new offspring through the crossover operation. There are two parent individuals x i and x j The linear combination of is:

[0088]

[0089] in, represents the new individual after crossover, which means the new offspring individual generated by the crossover operation, inheriting the genetic information of the two parent individuals; x irepresents one of the parent individuals, indicating the first parent individual selected for crossover operation in the genetic algorithm, and its genetic information will be partially passed to the offspring; x j represents the second parent individual, which means the second parent individual selected for crossover operation in the genetic algorithm, and its genetic information will also be partially passed on to the offspring; α represents the crossover ratio coefficient, which controls the proportion of genetic information inherited by the new individual from the two parent individuals; its value range is [0,1]. When α is equal to 0.5, the new individual will inherit the genetic information of the two parents on average; when α is close to 1, the new individual is closer to x i ; When α is close to 0, the new individual is closer to x j ; i and j represent the indexes of the first parent individual and the second parent individual respectively;

[0090] In the mutation stage, the genes of individuals will generate new gene combinations through random mutation operations, thereby enhancing population diversity. It is expressed as:

[0091]

[0092] in, represents the new individual obtained after mutation operation in genetic algorithm, x i represents the original individual before the mutation operation in the genetic algorithm, δ is a random variable, indicating the amplitude of the mutation; x max represents the maximum value allowed for the gene, x min Indicates the minimum allowed value of the gene, δ~N(0,σ 2 ) represents a normal distribution with a mean of 0 and a variance of σ 2 ; σ 2 The variance of the normal distribution, which indicates the magnitude of random variation in the mutation process;

[0093] Step 4: Optimize the preparation control operation of the barrier material;

[0094] According to the optimal ratio obtained by genetic algorithm optimization, the actuator controls the amount of raw materials added:

[0095]

[0096] Among them, Q i (t) represents the instantaneous amount of the i-th raw material at time t, m i (t) represents the total input mass of the i-th raw material at time t;

[0097] Mixing speed and time are controlled based on real-time viscosity feedback, and the mixing speed v(t) is adjusted based on the current viscosity and the target viscosity η * Ratio of:

[0098]

[0099] Where v(t) represents the stirring speed, η(t) represents the real-time viscosity of the mixed solution at time t, represents the function of stirring speed, η * Indicates the set target viscosity;

[0100] The barrier properties and viscosity of the mixed solution are calculated using the formula:

[0101] F(X new )=f(OTR,WVTR,Bio,Cost)

[0102] Among them, F(X new ) represents the fitness value of the new individual; X new represents the new generation of individuals generated by genetic operations such as crossover and mutation during the optimization process, f(OTR, WVTR, Bio, Cost) represents the objective function, OTR represents oxygen permeability, WVTR represents water vapor permeability, Bio represents biosafety, and Cost represents cost;

[0103] Step 5: Preparation of modified heat-resistant particles;

[0104] The temperature change in the reactor is expressed by the heat transfer equation:

[0105]

[0106] Among them, T react (t) represents the temperature in the reactor at time t, T0 represents the initial temperature of the reaction, Q represents the amount of heat transferred, m represents the mass of the solution, and c represents the specific heat capacity of the solution;

[0107] The pressure P(t) in the reactor is expressed according to the ideal gas state equation:

[0108]

[0109] Where P(t) represents the pressure in the reactor at time t, n represents the amount of the reaction gas, R represents the gas constant of the reaction gas, and T react (t) represents the temperature in the reactor at time t, and V represents the volume of the reactor;

[0110] The average particle size of the particles p (t) By detecting the particle size d of various particles i and its number n i The calculation results are:

[0111]

[0112] Among them, dp (t) represents the average particle size at time t, d i represents the particle size of the i-th type of particles, n i represents the number of particles of the i-th category, i represents the index variable, and n represents the total number of particle categories;

[0113] Effect of reaction temperature, time and pressure on the modification effect M p The impact of is predicted by the SVM model:

[0114] M p =f(T react (t),t react ,P(t))

[0115] Among them, M p Indicates the modification effect of particles, t react represents the reaction time, P(t) represents the pressure in the reactor at time t, T react (t) represents the temperature in the reactor at time t, f(T react (t),t react ,P(t)) represents the objective function for evaluating the modification effect of particles under different reaction conditions;

[0116] Effect of reaction conditions on particle size d p The influence of (t) is also predicted by the SVM model:

[0117] d p (t) = g(T react (t),t react ,P(t))

[0118] Among them, d p (t) represents the average particle size at time t, g(T react (t),t react , P(t)) represents the objective function of the reaction conditions affecting the particle size, t react represents the reaction time, P(t) represents the pressure in the reactor at time t, T react (t) represents the temperature in the reactor at time t;

[0119] Combining ant colony algorithm and differential evolution algorithm to optimize the parameters of SVM model:

[0120] The ant colony algorithm simulates the foraging process of ants and performs a global search in the parameter space to find a set of preliminary suitable C and γ parameter combinations;

[0121] Pheromone update: Ants use the accumulation and volatilization of pheromones to guide the next search during the search process:

[0122] τ i(t+1)=(1-ρ)τ i (t)+Δτ i (t)

[0123] Among them, τ i (t+1) represents the pheromone concentration on the i-th path at the t+1-th iteration; τ i (t) represents the pheromone concentration on the i-th path at the t-th iteration; ρ represents the pheromone volatility; Δτ i (t) represents the pheromone increment on the i-th path in the t-th iteration;

[0124] Probabilistic selection: Each ant chooses a path based on the pheromone concentration, that is, it chooses different parameter combinations:

[0125]

[0126] Among them, P i represents the probability of the i-th individual or path being selected, τ i (t) represents the pheromone concentration on the i-th path at the t-th iteration; τ k (t) represents the pheromone concentration on the kth path at the tth iteration, η i (t), η k (t) represents the heuristic information of the i-th and k-th paths, α represents the influencing factor of pheromone concentration, β represents the influencing factor of heuristic information, and m represents the total number of paths;

[0127] After the ant colony algorithm finds the initial suitable C and γ, the differential evolution algorithm further optimizes these parameters to find the final optimal value:

[0128]

[0129] in, represents the vector of the i-th individual in the g-th generation; represents the new vector generated after mutation, represents the vector of two different individuals randomly selected from the current population, F represents the mutation factor, which is between 0≤F≤20 and controls the amplitude of the mutation; rand represents a random number uniformly distributed between 0 and 1, which is used to decide whether to perform a crossover operation; CR represents the crossover probability, represents the new vector of the i-th individual in the g+1th generation, i.e., the solution for the next generation;

[0130] Minimize the objective function:

[0131]

[0132] Among them, Minimize(C,γ) means that the optimization goal is to minimize the function C represents the penalty parameter of SVM, γ represents the kernel function parameter, Represents the total error of the model on the training set; Represents the difference between the model prediction value and the actual value; y i Represents the true output of the i-th sample in the data set; Represents the predicted output of the model on the i-th sample; N represents the number of samples contained in the data set;

[0133] Step 6: Preparation control operation of optimized modified heat-resistant particles;

[0134] The reaction temperature is maintained in the optimal range by a PID controller:

[0135]

[0136] Where u(t) represents the control signal, which adjusts the output of the heating system, e(t) represents the error between the set temperature and the current temperature, and ∫e(t)dt represents the integral of the error signal. represents the differential of the error signal, K p , K i , K d Respectively represent the proportional, integral, and differential coefficients of the PID controller;

[0137] Reaction time t react The choice of is based on minimizing the error in the particle modification effect:

[0138]

[0139] Among them, t react represents the optimal response time, Represents the objective function The minimum time point, M p (t) represents the actual modification effect at time t; Indicates the target modification effect;

[0140] The temperature drop rate during the cooling process is expressed as:

[0141] T cool (t) = T react -k cool t

[0142] Among them, T cool (t) represents the temperature at time t during the cooling process, T react represents the temperature at the end of the reaction, k cool represents the cooling rate constant.

[0143] Example 1

[0144] This embodiment provides a medical packaging composite film and a preparation method thereof, which comprises the following raw material components by weight: 2 parts of chitosan, 0.5 parts of alanine, 0.15 parts of potassium sorbate, 0.5 parts of maltitol and 0.5 parts of poloxamer 188;

[0145] S110: fully dissolving 2 parts of chitosan, 0.5 parts of alanine, 0.15 parts of potassium sorbate, and 0.5 parts of maltitol in deionized water to obtain a pretreatment solution;

[0146] S120: dissolving 0.5 parts of poloxamer 188 in the pretreatment solution to obtain a barrier material;

[0147] S100: coating DP604NS on the first surface of the aluminum foil layer, laminating it with the barrier material, performing a drying process at a temperature of 75° C., and performing a calendering process at a temperature of 100° C. and a pressure of 75 MPa to obtain a barrier layer, an adhesive layer, and an aluminum foil layer;

[0148] A. mixing sodium carboxymethyl cellulose and water to obtain a thickener solution, and mixing polyacrylamide and water to obtain a first premix solution;

[0149] B. mixing the first premix solution and the thickener solution to obtain a second premix solution;

[0150] C. adding the modified heat-resistant particles into the second premixed liquid to obtain a third premixed liquid;

[0151] D. Mix the third premixed liquid with DP604NS to prepare a heat-sealing slurry.

[0152] S200: coating a heat-sealing slurry on the second surface of the aluminum foil layer, and performing a secondary drying process at a temperature of 75° C. to obtain a medical packaging composite film;

[0153] The preparation method of the heat-resistant particles includes: mixing alumina, water and polyetheretherketone, performing a hydrothermal reaction at 180°C for 6 hours, cooling, solid-liquid separation, and drying the obtained solid material to obtain modified heat-resistant particles, wherein the particle size of the modified heat-resistant particles is 1.0 μm;

[0154] The mass ratio of aluminum, iron and nickel in the aluminum foil layer is 99:0.5:0.5.

[0155] Example 2

[0156] This embodiment provides a medical packaging composite film and a preparation method thereof, which comprises the following raw material components by weight: 0.1 part of chitosan, 0.01 part of alanine, 0.1 part of potassium sorbate, 0.1 part of maltitol and 0.01 part of poloxamer 188;

[0157] S110: fully dissolving 0.1 parts of chitosan, 0.01 parts of alanine, 0.1 parts of potassium sorbate, and 0.1 parts of maltitol in deionized water to obtain a pretreatment solution;

[0158] S120: dissolving 0.01 parts of poloxamer 188 in the pretreatment solution to obtain a barrier material;

[0159] S100: coating DP604NS on the first surface of the aluminum foil layer, laminating it with a barrier material, performing a drying process at a temperature of 60° C., and performing a calendering process at a temperature of 50° C. and a pressure of 10 MPa to obtain a barrier layer, an adhesive layer, and an aluminum foil layer;

[0160] A. mixing sodium carboxymethyl cellulose and water to obtain a thickener solution, and mixing polyacrylamide and water to obtain a first premix solution;

[0161] B. mixing the first premix solution and the thickener solution to obtain a second premix solution;

[0162] C. adding the modified heat-resistant particles into the second premixed liquid to obtain a third premixed liquid;

[0163] D. Mix the third premixed liquid with DP604NS to prepare a heat-sealing slurry.

[0164] S200: coating a heat-sealing slurry on the second surface of the aluminum foil layer, and performing a secondary drying process at a temperature of 60° C. to obtain a medical packaging composite film;

[0165] The preparation method of the heat-resistant particles includes: mixing zirconium oxide, water and polyimide, performing a hydrothermal reaction at 160°C for 8 hours, cooling, solid-liquid separation, and drying the obtained solid material to obtain modified heat-resistant particles, wherein the particle size of the modified heat-resistant particles is 0.2 μm;

[0166] The mass ratio of aluminum, iron and nickel in the aluminum foil layer is 98.8:0.6:0.6.

[0167] Example 3

[0168] This embodiment provides a medical packaging composite film and a preparation method thereof, which comprises the following raw material components by weight: 5 parts of chitosan, 1 part of alanine, 0.2 parts of potassium sorbate, 1 part of maltitol and 1 part of poloxamer 188;

[0169] S110: fully dissolving 5 parts of chitosan, 1 part of alanine, 0.2 parts of potassium sorbate, and 1 part of maltitol in deionized water to obtain a pretreatment solution;

[0170] S120: fully dissolving one portion of poloxamer 188 in the pretreatment solution to obtain a barrier material;

[0171] S100: coating DP604NS on the first surface of the aluminum foil layer, laminating with the barrier material, performing a drying process at a temperature of 100° C., and performing a calendering process at a temperature of 150° C. and a pressure of 100 MPa to obtain a barrier layer, an adhesive layer, and an aluminum foil layer;

[0172] A. mixing sodium carboxymethyl cellulose and water to obtain a thickener solution, and mixing polyacrylamide and water to obtain a first premix solution;

[0173] B. mixing the first premix solution and the thickener solution to obtain a second premix solution;

[0174] C. adding the modified heat-resistant particles into the second premixed liquid to obtain a third premixed liquid;

[0175] D. Mix the third premixed liquid with DP604NS to prepare a heat-sealing slurry.

[0176] S200: coating a heat-sealing slurry on the second surface of the aluminum foil layer, and performing a secondary drying process at a temperature of 100° C. to obtain a medical packaging composite film;

[0177] The preparation method of the heat-resistant particles includes: mixing zirconium oxide, water and polyimide, performing a hydrothermal reaction at 200°C for 2 hours, cooling, solid-liquid separation, and drying the obtained solid material to obtain modified heat-resistant particles, wherein the particle size of the modified heat-resistant particles is 2 μm;

[0178] The mass ratio of aluminum, iron and nickel in the aluminum foil layer is 99.2:0.4:0.4.

[0179] In order to verify whether the medical packaging composite film of the present invention achieves the expected effect, the performance test of the present invention was carried out, and the results are as follows:

[0180] The specific thicknesses of the barrier layer, adhesive layer, aluminum foil layer, and heat-sealing layer of Examples 1-3 are shown in Table 1.

[0181] Table 1

[0182] project Barrier layer Adhesive layer Aluminum foil layer Heat seal layer Example 1 12μm 5μm 15μm 30μm Example 2 5μm 1μm 5μm 20μm Example 3 25μm 10μm 20μm 50μm

[0183] The moisture permeability, oxygen permeability, heat shrinkage rate and long-term use temperature of the medical composite packaging films of Examples 1-3 are shown in Table 1 and Table 2.

[0184] Table 2

[0185]

[0186] It can be seen from the above table that the moisture permeability of the present application is between 200-230gm-2h-1, the heat shrinkage rate is as low as 1.3%, it has excellent heat sealing performance, the oxygen permeability is as low as 0.4cm3 / m2·24h·0.1MPa or less, it has high barrier properties, and the maximum long-term use temperature is above 220°C. Therefore, it has excellent heat resistance and can meet the use of pharmaceutical packaging materials.

[0187] Example 4

[0188] Assume that the target ratio is chitosan 5 mg / L, alanine 0.5 mg / L, potassium sorbate 0.2 mg / L, maltitol 1 mg / L, and poloxamer 1880.5 mg / L;

[0189] The temperature of the dissolving tank is set to 50°C, the temperature of the mixing tank is set to 60°C, the temperature of the hydrothermal reactor is set to 160°C, the desired viscosity is 10Pa·s, the pressure in the reactor is set to 1MPa, and the average particle size of the target particles is 1μm;

[0190] Collection of sensor parameters;

[0191] According to the following formula, it can be calculated:

[0192]

[0193] Q=mcΔT

[0194]

[0195] The mass of chitosan m1(t) is 10 mg, and the volume of solution V(t) is 2 L, so the concentration of chitosan is 5 mg / L;

[0196] The heat transferred Q = 1000 J, the mass of the solution m = 0.5 kg, the specific heat c = 4.18 J / (kg·℃), the initial temperature T0 = 20℃, then the temperature after 10 minutes is: 67.87℃

[0197] Shear stress τ(t) = 50 Pa, shear rate Then the dynamic viscosity is: 10Pa·s;

[0198] Initial population generation:

[0199] X0={x i,0},x i,0 ∈[a i ,b i ]

[0200] The initial population size is 5, and the raw material ratio of each individual in the initial state is in the range [a i ,b i] were randomly generated within , and the range of chitosan was [4,6] mg / L; each individual contained the proportion of chitosan (mg / L), alanine (mg / L), potassium sorbate (mg / L), maltitol (mg / L), and poloxamer 188 (mg / L);

[0201] X1=(5.0,0.5,0.15,0.8,0.4)

[0202] X2=(4.8, 0.6, 0.1, 0.9, 0.5)

[0203] X3=(5.2,0.4,0.2,0.7,0.6)

[0204] X4=(5.1,0.45,0.18,0.75,0.55)

[0205] X5=(4.9,0.55,0.12,0.85,0.45)

[0206] According to the comprehensive objective function definition:

[0207]

[0208] Assuming that the OTR of the ratio combination is 0.2, WVTR is 0.5, Bio is 95%, and Cost is 10, the objective function value is:

[0209]

[0210] Through operations such as selection, crossover, and mutation, we can obtain:

[0211]

[0212]

[0213] In the crossover phase, the selected individuals generate new offspring through the crossover operation. Suppose we select individuals 1 and 4 for crossover, and the crossover ratio coefficient is α = 0.6. The new individual X after crossover is new .

[0214] X new =(5.06,0.48,0.162,0.78,0.46)

[0215] In the mutation phase, the genes of individuals will generate new gene combinations through random mutation operations. Suppose we have the individual X generated after crossover. new Perform mutation operation, assuming the mutation rate is 10%, random variable δ~N(0,σ 2 ), where σ = 0.05, the allowed chitosan concentration range is [4.5, 5.5] mg / L, and δ = 0.03.

[0216] The new individual after the final mutation:

[0217] X mut =(5.09,0.48,0.162,0.78,0.46)

[0218] According to the optimal ratio obtained by genetic algorithm optimization, the actuator controls:

[0219]

[0220]

[0221] F(X new )=f(OTR,WVTR,Bio,Cost)

[0222] The optimal ratio is chitosan 5 mg / L, alanine 0.5 mg / L, potassium sorbate 0.2 mg / L, maltitol 1 mg / L, and poloxamer 1880.5 mg / L; the instantaneous chitosan dosage Q1(t) of the control system is 0.05 kg / h, and the total dosage m1(t) is 0.1 kg; the mixing speed is adjusted based on viscosity feedback, the current viscosity is 9 Pa·s, and the target viscosity is 10 Pa·s, then the stirring speed increases; after mixing, the OTR, WVTR, Bio and Cost of the barrier material are tested. If the objective function value reaches 2.4, the ratio is considered qualified.

[0223] Preparation of modified heat-resistant particles;

[0224] The state information after a period of reaction can be calculated according to the following formula:

[0225]

[0226]

[0227]

[0228] The initial reaction temperature is 160°C, the mass of the solution is 1kg, the specific heat capacity is 4.18J / (kg·°C), and the heat transferred is 2000J. Then the temperature after 20 minutes is: 176.87°C;

[0229] The pressure is calculated according to the ideal gas state equation, assuming that the amount of the reaction gas n = 1 mol, the gas constant R = 8.314 J / (mol·K), and the reactor volume V = 0.01 m 3 , then the pressure is: 0.374MPa;

[0230] Assuming that most of the particles in the initial particle size are concentrated around 1.5 μm, at 20 seconds, the average particle size of the particles is 1.0105 μm, which is close to the target particle size.

[0231] The model uses temperature, time and pressure as input to predict the modification effect M p as output.

[0232] Initial setting parameter range: C is between [0.1, 100], γ is between [0.001, 10]. Assuming the initial C = 1 and γ = 0.1, use ACO and DE to optimize these parameters. After several iterations, the optimal parameters C = 10, γ = 0.05 are found;

[0233] After optimization by ant colony algorithm and differential algorithm: a global search is performed in the parameter space to find a set of preliminary suitable C and γ parameter combinations;

[0234] τ i (t+1)=(1-ρ)τ i (t)+Δτ i (t)

[0235]

[0236]

[0237] Assuming that the initial pheromone concentration of the four paths is 1.0, the pheromone volatilization rate ρ=0.1, the pheromone increments of each path after the first iteration are 0.5, 0.3, 0.7, and 0.2 respectively; through the pheromone update formula, the pheromone concentrations of the second iteration are calculated to be 1.4, 1.2, 1.6, and 1.1 respectively;

[0238] Assume that the heuristic information η of the four paths i (t) is 0.8, 0.7, 0.9, 0.6; pheromone influence factor α = 1.0, heuristic information influence factor β = 2.0; the calculated probability of each path being selected is 0.338, 0.222, 0.489, 0.149; through probabilistic selection, path 3 has the highest probability of being selected, which means that the current ant is more likely to choose the parameter combination of path 3 in the next iteration.

[0239] Assume that the optimal parameter combination initially determined in ACO is: C = 15 and γ = 0.1;

[0240] The differential evolution algorithm (DE) was further optimized, assuming that the mutation factor F = 0.5, the crossover probability CR = 0.9 and the random number was 0.8 (less than CR) to obtain the optimal parameters C = 10 and γ = 0.05;

[0241] Under the optimal parameters C = 10 and γ = 0.05, the SVM model predicted the following optimal reaction conditions: optimal reaction temperature: 165 ° C, optimal reaction time: 60 minutes, optimal pressure: 7.2 MPa. Under these conditions, the modification effect predicted by the model is Close to the target value.

[0242] The optimized preparation control operation of modified heat-resistant particles is inferred according to the following formula:

[0243]

[0244]

[0245] T cool (t) = T react -k cool t

[0246] Assume that the target temperature is 180°C and the current temperature is 170°C, so the error is 10°C; the output signal u(t) of the PID controller is calculated by the formula:

[0247] u(t)=u p (t)+u i (t)+u d (t) = 20 + 0 + 0.1 = 20.1 units

[0248] Under PID control (by manually adjusting PID related parameters), the temperature reaches 179°C after 5 minutes; at this time, the error is 1°C, and the control signal is reduced to: 2.02 units; finally, after 10 minutes, the temperature stabilizes at 180°C, and the control signal u(t) is reduced to the minimum value required to maintain temperature stability

[0249] In order to ensure the best modification effect of the particles, the reaction time was set to 60 minutes. The target modification effect was: After 60 minutes of reaction, the modification effect reached 0.9025, close to the target effect;

[0250] The temperature drop during cooling, T react =180℃, cooling rate k cool =0.5℃ / min;

[0251] Through PID control, the reaction temperature was precisely maintained at 180°C. After 60 minutes of reaction, the modification effect of the particles was close to the target value of 0.95. Subsequently, during the cooling process, the temperature decreased at a rate of 0.5°C / min, and after 10 minutes the temperature dropped to 175°C.

[0252] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a medical packaging composite film, characterized in that: The preparation method of the medical composite membrane comprises the following steps: S100: coating an adhesive on the first surface of the aluminum foil layer, laminating it with a barrier material, and sequentially performing a drying process and a calendering process to obtain a barrier layer, an adhesive layer, and an aluminum foil layer; S200: coating a heat-sealing slurry on the second surface of the aluminum foil layer and performing secondary drying to obtain the medical packaging composite film; The method for preparing the barrier material comprises the following steps: S110: fully dissolving chitosan, alanine, potassium sorbate, and maltitol with deionized water to obtain a pretreatment solution; S120: fully dissolving poloxamer 188 in the pretreatment solution to obtain the barrier material; The adhesive includes: polyurethane adhesive or acrylate adhesive; The heat sealing slurry comprises the following raw material components by weight: 20-35 parts of modified heat-resistant particles, 0.01-1 parts of dispersant, 1-5 parts of binder, 0.1-3 parts of thickener and 50-75 parts of water; The modified heat-resistant particles are obtained by modifying the modified heat-resistant particles with a modifier; the modifier includes polyetheretherketone and polyimide.

2. The preparation method according to claim 1, characterized in that: S110 includes the following raw material components by weight: 0.1-5 parts of chitosan, 0.01-1 parts of alanine, 0.1-0.2 parts of potassium sorbate, 0.1-1 parts of maltitol and 0.01-1 parts of poloxamer 188; S110 includes the following raw material components by weight: 2 parts of chitosan, 0.5 parts of alanine, 0.15 parts of potassium sorbate, 0.5 parts of maltitol and 0.5 parts of poloxamer 188.

3. The preparation method according to claim 1, characterized in that: The preparation method of the heat sealing slurry comprises the following steps: A. mixing the thickener and water to obtain a thickener solution, and mixing the dispersant and water to obtain a first premix solution; B. mixing the first premix solution and the thickener solution to obtain a second premix solution; C. adding the modified heat-resistant particles into the second premixed liquid to obtain a third premixed liquid; D. Mixing the third premixed liquid with the adhesive to prepare the heat sealing slurry.

4. The preparation method according to claim 3, characterized in that: The preparation method of the modified heat-resistant particles comprises: The heat-resistant particles, water and the modifier are mixed, and a hydrothermal reaction is carried out at 160° C.-200° C. for 2 h-8 h, followed by cooling and solid-liquid separation, and the obtained solid material is dried to obtain the modified heat-resistant particles.

5. The preparation method according to claim 1, characterized in that: The modified heat-resistant particles include at least one of aluminum oxide, zirconium oxide and silicon dioxide; and / or The particle size of the modified heat-resistant particles is 0.2 μm-2.0 μm; and / or The thickener is a carboxymethyl cellulose thickener; and / or The dispersant is an aqueous polymer dispersant.

6. The preparation method according to claim 1, characterized in that: In S100, the temperature of the primary drying process is 60-100°C; and / or In S100, the temperature of the calendering treatment is 50-150°C; and / or In S100, the pressure of the calendering treatment is 10-100 MPa; and / or In S200, the temperature of the secondary drying process is 60-100°C.

7. The preparation method according to claim 1, characterized in that: The aluminum foil layer includes aluminum, iron, and nickel; wherein the mass ratio of the aluminum, iron, and nickel is (98.8-99.2):(0.4-0.6):(0.4-0.6).

8. The preparation method according to claim 1, characterized in that: The thickness of the barrier layer is 5 μm to 25 μm; and / or The thickness of the adhesive layer is 1 μm to 10 μm; and / or The thickness of the aluminum foil layer is 5 μm to 20 μm; and / or The thickness of the heat sealing layer is 20 μm to 50 μm.

9. The preparation method according to claim 1, characterized in that: It also includes optimizing and controlling the preparation method of the barrier material and the preparation method of the modified heat-resistant particles through an intelligent control algorithm. The specific steps are as follows: Step 1: Installation of sensor; Component concentration sensor: Install high-precision electrochemical concentration sensors in the chitosan, alanine, potassium sorbate, maltitol, and poloxamer 188 raw material dissolution tanks to monitor the concentration of each raw material in real time to ensure accurate raw material ratios during the mixing process; Temperature sensor: High-precision temperature sensors are installed in the dissolving tank, mixing tank and hydrothermal reactor to monitor and control the temperature in each process step to ensure the stability of the dissolving and mixing process; Viscosity sensor: A rotational viscometer is installed in the final mixing tank to monitor the viscosity of the mixed barrier material solution to ensure that it meets the process requirements; Pressure sensor: Install a piezoelectric pressure sensor in the reactor; Particle size sensor: An online detection device equipped with a laser particle size analyzer after the reaction to detect the particle size distribution of the modified heat-resistant particles in real time; Step 2: Collection of sensor parameters; The concentration of each raw material can be expressed by the following formula: Among them, C i (t) represents the concentration of the i-th raw material at time t, m i (t) represents the mass of the i-th raw material at time t, and V(t) represents the volume of the solution at time t; Temperature control is calculated using the following heat transfer equation: Q=mcΔT Where Q represents the amount of heat transferred, m represents the mass of the solution, c represents the specific heat capacity of the solution, and ΔT represents the temperature change; The calculation formula of dynamic viscosity is: Where η(t) represents the dynamic viscosity of the fluid at time t, τ represents the shear stress, represents the shear rate; Step 3: Preparation and optimization of barrier materials; The optimization algorithm GA based on natural selection and genetic mechanism generates different raw material ratio combinations through operations such as selection, crossover, and mutation. The improved sparrow search algorithm ISSA is used to enhance the local search ability of GA to avoid falling into the local optimum. It improves the optimization efficiency by adaptively adjusting the step size and direction. Initial population generation: X0={x i,0 },x i,0 ∈[a i ,b i ] Among them, X0 represents the initial population, x i,0 represents the raw material ratio of the i-th individual in its initial state, 0 represents the 0th generation individual of the initial population, and a i Indicates the lower limit of the raw material ratio, b i Indicates the upper limit of the raw material ratio; Comprehensive objective function definition: Among them, F(X) represents the comprehensive objective function, which is used to evaluate the advantages and disadvantages of different material ratios; X represents the material ratio scheme; OTR(X) is the oxygen permeability, which indicates the speed at which the material allows oxygen to pass through; WVTR(X) is the water vapor permeability, which indicates the speed at which the material allows water vapor to pass through. The lower the water vapor permeability, the better the barrier performance of the material; Bio(X) is biosafety, which indicates the compatibility of the material with the biological system. The higher the biosafety, the better; Cost(X) is the material cost, which indicates the cost of manufacturing the material; w1, w2, w3, and w4 are weight coefficients, which are used to adjust the relative importance of each target in the comprehensive objective function; In the selection phase, the genetic algorithm determines which individuals will be retained for crossover operations through the selection operator, and the selection probability P i Based on individual fitness F(X i )Sure: Among them, P i represents the probability of the i-th individual being selected; F(X i ) represents the fitness value of the i-th individual, represents the sum of the fitness values ​​of all individuals, j represents the index of an individual in the current population, and N represents the total number of individuals in the population; In the crossover phase, the selected individuals generate new offspring through the crossover operation. There are two parent individuals x i and x j The linear combination of is: in, represents the new individual after crossover, which means the new offspring individual generated by the crossover operation, inheriting the genetic information of the two parent individuals; x i represents one of the parent individuals, indicating the first parent individual selected for crossover operation in the genetic algorithm, and its genetic information will be partially passed to the offspring; x j represents the second parent individual, which means the second parent individual selected for crossover operation in the genetic algorithm, and its genetic information will also be partially passed on to the offspring; α represents the crossover ratio coefficient, which controls the proportion of genetic information inherited by the new individual from the two parent individuals; its value range is [0,1]. When α is equal to 0.5, the new individual will inherit the genetic information of the two parents on average; when α is close to 1, the new individual is closer to x i ; When α is close to 0, the new individual is closer to x j ; i and j represent the indexes of the first parent individual and the second parent individual respectively; In the mutation stage, the genes of individuals will generate new gene combinations through random mutation operations, thereby enhancing population diversity. It is expressed as: in, represents the new individual obtained after mutation operation in genetic algorithm, x i represents the original individual before the mutation operation in the genetic algorithm, δ is a random variable, indicating the amplitude of the mutation; x max represents the maximum value allowed for the gene, x min Indicates the minimum allowed value of the gene, δ~N(0,σ 2 ) represents a normal distribution with a mean of 0 and a variance of σ 2 ; σ 2 The variance of the normal distribution, which indicates the magnitude of random variation in the mutation process; Step 4: Optimize the preparation control operation of the barrier material; According to the optimal ratio obtained by genetic algorithm optimization, the actuator controls the amount of raw materials added: Among them, Q i (t) represents the instantaneous amount of the i-th raw material at time t, m i (t) represents the total input mass of the i-th raw material at time t; Mixing speed and time are controlled based on real-time viscosity feedback, and the mixing speed v(t) is adjusted based on the current viscosity and the target viscosity η * Ratio of: Where v(t) represents the stirring speed, η(t) represents the real-time viscosity of the mixed solution at time t, is a function of the stirring speed, η * Indicates the set target viscosity; The barrier properties and viscosity of the mixed solution are calculated using the formula: F(X new )=f(OTR,WVTR,Bio,Cost) Among them, F(X new ) represents the fitness value of the new individual; X new represents the new generation of individuals generated by genetic operations such as crossover and mutation during the optimization process, f(OTR, WVTR, Bio, Cost) represents the objective function, OTR represents oxygen permeability, WVTR represents water vapor permeability, Bio represents biosafety, and Cost represents cost; Step 5: Preparation of modified heat-resistant particles; The temperature change in the reactor is expressed by the heat transfer equation: Among them, T react (t) represents the temperature in the reactor at time t, T0 represents the initial temperature of the reaction, Q represents the amount of heat transferred, m represents the mass of the solution, and c represents the specific heat capacity of the solution; The pressure P(t) in the reactor is expressed according to the ideal gas state equation: Where P(t) represents the pressure in the reactor at time t, n represents the amount of the reaction gas, R represents the gas constant of the reaction gas, and T react (t) represents the temperature in the reactor at time t, and V represents the volume of the reactor; The average particle size of the particles p (t) By detecting the particle size d of various particles i and its number n i The calculation results are: Among them, d p (t) represents the average particle size at time t, d i represents the particle size of the i-th type of particles, n i represents the number of particles of the i-th category, i represents the index variable, and n represents the total number of particle categories; Effect of reaction temperature, time and pressure on the modification effect M p The impact of is predicted by the SVM model: M p =f(T react (t),t react ,P(t)) Among them, M p Indicates the modification effect of particles, t react represents the reaction time, P(t) represents the pressure in the reactor at time t, T react (t) represents the temperature in the reactor at time t, f(T react (t),t react ,P(t)) represents the objective function for evaluating the modification effect of particles under different reaction conditions; Effect of reaction conditions on particle size d p The influence of (t) is also predicted by the SVM model: d p (t)=g(T react (t),t react ,P(t)) Among them, d p (t) represents the average particle size at time t, g(T react (t),t react , P(t)) represents the objective function of the reaction conditions affecting the particle size, t react represents the reaction time, P(t) represents the pressure in the reactor at time t, T react (t) represents the temperature in the reactor at time t; Combining ant colony algorithm and differential evolution algorithm to optimize the parameters of SVM model: The ant colony algorithm simulates the foraging process of ants and performs a global search in the parameter space to find a set of preliminary suitable C and γ parameter combinations; Pheromone update: Ants use the accumulation and volatilization of pheromones to guide the next search during the search process: t i (t+1)=(1-ρ)τ i (t)+Δτ i (t) Among them, τ i (t+1) represents the pheromone concentration on the i-th path at the t+1-th iteration; τ i (t) represents the pheromone concentration on the i-th path at the t-th iteration; ρ represents the pheromone volatility; Δτ i (t) represents the pheromone increment on the i-th path in the t-th iteration; Probabilistic selection: Each ant chooses a path based on the pheromone concentration, that is, it chooses different parameter combinations: Among them, P i represents the probability of the i-th individual or path being selected, τ i (t) represents the pheromone concentration on the i-th path at the t-th iteration; τ k (t) represents the pheromone concentration on the kth path at the tth iteration, η i (t), η k (t) represents the heuristic information of the i-th and k-th paths, α represents the influencing factor of pheromone concentration, β represents the influencing factor of heuristic information, and m represents the total number of paths; After the ant colony algorithm finds the initial suitable C and γ, the differential evolution algorithm further optimizes these parameters to find the final optimal value: in, represents the vector of the i-th individual in the g-th generation; represents the new vector generated after mutation, represents the vector of two different individuals randomly selected from the current population, F represents the mutation factor, which is between 0≤F≤20 and controls the amplitude of the mutation; rand represents a random number uniformly distributed between 0 and 1, which is used to decide whether to perform a crossover operation; CR represents the crossover probability, represents the new vector of the i-th individual in the g+1th generation, i.e., the solution for the next generation; Minimize the objective function: Among them, Minimize(C,γ) means that the optimization goal is to minimize the function C represents the penalty parameter of SVM, γ represents the kernel function parameter, Represents the total error of the model on the training set; Represents the difference between the model prediction value and the actual value; y i Represents the true output of the i-th sample in the data set; Represents the predicted output of the model on the i-th sample; N represents the number of samples contained in the data set; Step 6: Preparation control operation of optimized modified heat-resistant particles; The reaction temperature is maintained in the optimal range by a PID controller: Where u(t) represents the control signal, which adjusts the output of the heating system, e(t) represents the error between the set temperature and the current temperature, and ∫e(t)dt represents the integral of the error signal. represents the differential of the error signal, K p , K i , K d Respectively represent the proportional, integral, and differential coefficients of the PID controller; Reaction time t react The choice of is based on minimizing the error in the particle modification effect: Among them, t react represents the optimal response time, Represents the objective function The minimum time point, M p (t) represents the actual modification effect at time t; Indicates the target modification effect; The temperature drop rate during the cooling process is expressed as: T cool (t)=T react -k cool t Among them, T cool (t) represents the temperature at time t during the cooling process, T react represents the temperature at the end of the reaction, k cool represents the cooling rate constant.

10. A medical packaging composite film, characterized in that: The medical packaging composite film is prepared according to the preparation method according to any one of claims 1 to 9.

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