A heat-seal medicine packaging film, a preparation method thereof and application thereof in low-temperature heat sealing of medicines

Abstract

The application belongs to the technical field of medicine packaging film, and discloses a heat-sealing medicine packaging film, a preparation method thereof and application of the heat-sealing medicine packaging film in low-temperature heat-sealing of medicines. The packaging film comprises an outer layer, a barrier layer and a heat-sealing layer which are sequentially compounded. The heat-sealing surface of the heat-sealing layer is provided with a super-hydrophobic micro-nano layer, and pressure-temperature dual-triggered color-developing microcapsules are uniformly dispersed in the heat-sealing layer. The preparation method comprises the steps of raw material mixing, melt extrusion casting, solvent-free compounding and curing and cutting. When applied, the heat-sealing temperature is 68-78 DEG C. The packaging film can effectively prevent the contents from adhering, realize heat-sealing quality visualization, is safe and non-toxic, simple in process, suitable for industrialized production, and can be widely applied to low-temperature heat-sealing packaging of various heat-sensitive medicines.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical packaging film technology, specifically relating to a heat-sealing pharmaceutical packaging film, its preparation method, and its application in low-temperature heat sealing of pharmaceuticals. Background Technology

[0002] Pharmaceutical packaging is a crucial component of the pharmaceutical quality assurance system, directly impacting the storage stability and safety of medications. Heat sealing, as a core process in the production of flexible pharmaceutical packaging, directly determines the sealing performance of the packaging. With the rapid development of biopharmaceuticals and the modernization of traditional Chinese medicine, an increasing number of heat-sensitive drugs (such as probiotics, vitamins, and traditional Chinese medicine extracts) are placing stringent requirements on heat sealing temperatures. Low-temperature heat-sealing pharmaceutical packaging films have become the mainstream direction for industry development.

[0003] Currently, low-temperature heat-sealing pharmaceutical packaging films on the market mainly reduce the heat-sealing temperature by adding low-melting-point resin to the heat-sealing layer, which can basically meet the low-temperature heat-sealing requirements of 70-80℃. However, in actual production applications, there are still some problems that need to be solved by the existing technology.

[0004] Firstly, for traditional Chinese medicine granules, syrups, ointments, and other easily adhesive contents, the contents are very likely to adhere to the sealing surface during the heat sealing process, forming a layer of trapped material, leading to incomplete sealing and leakage, which seriously affects the shelf life and safety of the medicine. To solve this problem, the industry usually adopts the method of adding a slip agent to the heat sealing layer. However, the slip agent will gradually migrate to the surface, which will not only reduce the heat sealing strength, but also pose a safety risk of migrating into the medicine.

[0005] Secondly, current heat-sealing quality inspection mainly relies on manual sampling and online visual inspection equipment. Manual sampling is inefficient and has a high rate of missed inspections, making it impossible to guarantee the sealing quality of every package. Online visual inspection equipment is expensive and easily affected by environmental factors such as light and dust, resulting in a high rate of misjudgment.

[0006] Furthermore, existing testing methods can only detect surface defects and cannot determine the adhesion inside the seal, posing a significant quality hazard. Summary of the Invention

[0007] In view of the problems raised in the background art above, the purpose of this invention is to provide a heat-sealing pharmaceutical packaging film, its preparation method, and its application in low-temperature heat sealing of pharmaceuticals.

[0008] To achieve the above-mentioned technical objectives, the technical solution adopted by the present invention is as follows: A heat-sealable pharmaceutical packaging film includes an outer layer, a barrier layer, and a heat-sealable layer sequentially laminated together. The heat-sealable layer has a superhydrophobic micro / nano layer on its heat-sealable surface, and pressure-temperature dual-trigger colorimetric microcapsules are uniformly dispersed inside the heat-sealable layer. A method for preparing a heat-sealable pharmaceutical packaging film includes the following steps: S1. Mix the heat-sealing layer material evenly; S2. Melt extrusion casting to form a film, and at the same time, the structure is replicated onto the heat-sealing layer heat-sealing surface through a cooling roller with the superhydrophobic micro-nano layer; S3. Solvent-free composite of the outer layer, the barrier layer and the heat-sealing layer; S4. After ripening, the product is cut to obtain the finished product; An application of a heat-sealing pharmaceutical packaging film in low-temperature heat sealing of pharmaceuticals, wherein the heat sealing temperature is 68-78℃.

[0009] Further specifying, the outer layer is a PET, BOPP, or PA film with a thickness of 10-25μm; the barrier layer is an aluminum foil, alumina-plated PET, silicon oxide-plated PET, or EVOH film with a thickness of 6-15μm. This expands the material selection range for the outer layer and barrier layer, covering all mainstream pharmaceutical packaging composite film structures currently on the market. This avoids the reduction in protection range caused by limiting to a single material, while ensuring the mechanical and barrier properties of the product.

[0010] Further specifying, the heat-sealing layer matrix is ​​a blend of metallocene linear low-density polyethylene and ethylene-vinyl acetate copolymer, wherein the vinyl acetate content of the ethylene-vinyl acetate copolymer is 16-24%, and the blending mass ratio is 8:2-5:5. This clarifies the composition and parameters of the heat-sealing layer matrix resin. The metallocene linear low-density polyethylene provides good mechanical strength and heat-sealing performance, while the ethylene-vinyl acetate copolymer further reduces the heat-sealing temperature. This ratio range has been verified through industrial production and can achieve the best low-temperature heat-sealing effect.

[0011] Further defined, the superhydrophobic micro / nano layer has a water contact angle ≥145° and a roll-off angle ≤12°, and is composed of an array of micro-protrusions with a height of 3-12μm and a spacing of 15-35μm. This defines the key performance parameters and structural features of the superhydrophobic micro / nano layer. The water contact angle and roll-off angle ensure the anti-sticking effect, and the height and spacing range of the micro-protrusions take into account both the anti-sticking performance and the fabrication difficulty, making it easy for industrial production.

[0012] Further specified, the pressure-temperature dual-trigger colorimetric microcapsules have a particle size of 0.5-4μm, a shell made of food-grade polyurea or melamine-formaldehyde resin, and a core material made of a mixture of colorless crystal violet lactone and an acidic colorimetric agent. The amount of the pressure-temperature dual-trigger colorimetric microcapsules added is 4-9wt% of the total mass of the heat-sealing layer. The particle size, shell material, core material composition, and addition amount of the microcapsules are clearly defined. The food-grade shell material ensures the safety of the drug. This particle size range can ensure that the microcapsules are uniformly dispersed in the resin and can also ensure smooth rupture under heat-sealing pressure. The addition amount range takes into account both the colorimetric effect and the production cost.

[0013] Further specified, the thickness of the heat-sealing layer is 20-40μm, and the heat-sealing layer also contains 0.1-0.6wt% antioxidant and 0.05-0.4wt% slip agent, which account for 0.1-0.6wt% of the total mass of the heat-sealing layer. This limits the thickness of the heat-sealing layer and the amount of additives. This thickness range can provide sufficient heat-sealing strength and processing performance. The antioxidant prevents the resin from aging during processing, and the slip agent improves the opening properties of the film. The addition amounts are all within the industry's optimal range.

[0014] Further specified, in step S1, mixing is carried out at 300-500 rpm for 5-10 minutes; in step S2, the extrusion temperature is 115-145℃ and the cooling roller temperature is 15-30℃; in step S3, the coating amount is 1.2-2.3 g / m² and the compounding temperature is 45-65℃; in step S4, curing is carried out at 35-50℃ for 12-72 hours. The key process parameters of the preparation method are clearly defined, and all parameters are within the actual feasible range for industrial production, which can ensure the stability and consistency of product quality, while avoiding the limitation of protection range caused by overly narrow parameters.

[0015] Further specified, the heat sealing pressure is 0.15-0.35 MPa, the heat sealing time is 0.2-0.6 seconds, and the drugs include traditional Chinese medicine granules, syrups, ointments, vitamin preparations, probiotic preparations and antibiotic preparations, clarifying the application process parameters and applicable drug types.

[0016] The beneficial effects of using the present invention are as follows: 1. By constructing a superhydrophobic micro-nano layer on the surface of the heat-sealing layer, the contents such as Chinese medicine granules, syrups, and ointments cannot adhere to the sealing surface, fundamentally solving the problem of sealing failure caused by material trapping. The sealing qualification rate has been increased from 85% of the existing technology to over 99.5%, effectively preventing the adhesion of contents and significantly reducing the leakage rate of trapped materials.

[0017] 2. After heat sealing, the seal will automatically show color, allowing workers to judge the heat sealing quality with the naked eye. The defect rate is reduced by more than 98%, and expensive online inspection equipment is eliminated, significantly reducing production costs and realizing visualization of heat sealing quality without the need for additional inspection equipment.

[0018] 3. This method does not add any migratory chemical additives. The microcapsules are completely encapsulated inside the heat-sealing layer and will not come into direct contact with the drug. Accelerated aging test verification shows that the migration of microcapsules is below the detection limit, which meets the requirements of YBB00152002 "General Rules for Pharmaceutical Composite Films and Bags".

[0019] 4. This solution can be produced directly using existing casting composite equipment. Only the cooling roller with micro-nano structure needs to be replaced. The equipment modification cost is low, and the production efficiency is comparable to that of ordinary heat-sealing film, making it suitable for large-scale promotion and application.

[0020] 5. The heat sealing starting temperature of this solution is 68℃, and the heat sealing strength is ≥8N / 15mm. It can meet the low-temperature heat sealing requirements of various heat-sensitive drugs, with a wide heat sealing window and strong process adaptability. Attached Figure Description

[0021] The present invention can be further illustrated by the non-limiting embodiments given in the accompanying drawings; Figure 1 This is a cross-sectional structural diagram of an embodiment of a heat-sealed pharmaceutical packaging film according to the present invention; The symbols for the main components are explained below: Outer layer 1; Barrier layer 2; Heat-sealing layer 3; Superhydrophobic micro / nano layer 4; Pressure-temperature dual-trigger colorimetric microcapsule 5. Detailed Implementation

[0022] To enable those skilled in the art to better understand the present invention, the technical solution of the present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[0023] like Figure 1 As shown, a heat-sealed pharmaceutical packaging film of the present invention includes an outer layer 1, a barrier layer 2 and a heat-sealing layer 3 sequentially laminated together. The heat-sealing layer 3 has a superhydrophobic micro-nano layer 4 on its heat-sealing surface, and pressure-temperature dual-trigger color-developing microcapsules 5 are uniformly dispersed inside the heat-sealing layer 3. A method for preparing a heat-sealable pharmaceutical packaging film includes the following steps: S1. Mix the heat-sealing layer 3 materials evenly; S2, melt extrusion casting to form a film, and at the same time, the structure is replicated onto the heat-sealing layer 3 heat-sealing surface through a cooling roller with superhydrophobic micro-nano layer 4; S3. Solvent-free composite of outer layer 1, barrier layer 2 and heat-sealing layer 3; S4. After ripening, the product is cut to obtain the finished product; An application of a heat-sealing pharmaceutical packaging film in low-temperature heat sealing of pharmaceuticals, wherein the heat sealing temperature is 68-78℃. Example

[0024] This embodiment provides a heat-sealable pharmaceutical packaging film, which is composed of an outer layer 1, a barrier layer 2, and a heat-sealing layer 3 sequentially laminated together. The outer layer 1 is a 12μm thick PET film, the barrier layer 2 is an 7μm thick aluminum foil, and the heat-sealing layer 3 is 30μm thick. The heat-sealing layer 3 has an integrally formed superhydrophobic micro / nano layer 4, which is composed of an array of micro-protrusions with a height of 8μm and a spacing of 25μm, with a water contact angle of 150° and a roll-off angle of 8°. Pressure-temperature dual-trigger colorimetric microcapsules 5 are uniformly dispersed inside the heat-sealing layer 3. The microcapsules 5 have a particle size of 2 μm, a food-grade polyurea shell, and a core material that is a mixture of colorless crystal violet lactone and bisphenol A, with an addition amount of 6 wt% of the total mass of the heat-sealing layer. The matrix resin of the heat-sealing layer 3 is a blend of metallocene linear low-density polyethylene and ethylene-vinyl acetate copolymer, wherein the vinyl acetate content of the ethylene-vinyl acetate copolymer is 18%, and the blending mass ratio is 7:3. The heat-sealing layer 3 also contains 0.3 wt% antioxidant 1010 and 0.2 wt% slip agent erucamide, accounting for 0.3 wt% of the total mass of the heat-sealing layer.

[0025] The preparation method is as follows: S1. Accurately weigh 70 parts of metallocene linear low-density polyethylene, 30 parts of ethylene-vinyl acetate copolymer, 5-6.4 parts of pressure-temperature dual-trigger colorimetric microcapsules, 0.3 parts of antioxidant 1010, and 0.2 parts of slip agent erucamide. Add all raw materials to a high-speed mixer and mix at 400 rpm for 8 minutes at an ambient temperature of 25°C to obtain a mixture. S2. Add the mixture to the twin-screw extruder. Set the temperatures of each zone of the extruder to 115℃, 120℃, 125℃, 130℃, 135℃, and 130℃ respectively. Control the die temperature at 130℃. After the material is melted and plasticized, it is cast to the surface of the cooling roller through the T-die. Set the temperature of the cooling roller to 20℃. Control the production line speed at 15m / min. The surface of the cooling roller is pre-engraved with micro-protrusions corresponding to the superhydrophobic micro-nano layer 4 using laser engraving. During the casting process, the structure is directly copied to the heat-sealing layer 3. After cooling and shaping, the heat-sealing layer 3 master roll is obtained by winding. S3. The outer layer 1, barrier layer 2 and heat-sealing layer 3 are bonded together by a solventless bonding process. The solventless adhesive is polyurethane type, the amount of adhesive applied is controlled at 1.8g / m², the bonding temperature is 55℃ and the bonding pressure is 0.3MPa. S4. The composite film roll is sent into the curing chamber and cured at 40°C for 24 hours. Finally, it is cut into finished film rolls with a width of 1000mm by a slitting machine. Example

[0026] This embodiment provides a heat-sealing pharmaceutical packaging film, which is composed of an outer layer 1, a barrier layer 2, and a heat-sealing layer 3 sequentially laminated together. The outer layer 1 is a 25μm thick BOPP film, the barrier layer 2 is a 15μm thick alumina-coated PET film, and the heat-sealing layer 3 is 40μm thick. A superhydrophobic micro / nano layer 4 is integrally formed on the heat-sealing surface of the heat-sealing layer 3. The superhydrophobic micro / nano layer 4 is composed of an array of micro-protrusions with a height of 12μm and a spacing of 35μm, exhibiting a water contact angle of 145° and a roll-off angle of 12°. Pressure-temperature dual-trigger display elements are uniformly dispersed within the heat-sealing layer 3. Microcapsules 5 have a particle size of 4 μm, a food-grade polyurea shell, and a core material that is a mixture of colorless crystal violet lactone and salicylic acid. The amount added is 9 wt% of the total mass of the heat-sealing layer. The matrix resin of the heat-sealing layer 3 is a blend of metallocene linear low-density polyethylene and ethylene-vinyl acetate copolymer, wherein the vinyl acetate content of the ethylene-vinyl acetate copolymer is 24%, and the blending mass ratio is 5:5. The heat-sealing layer 3 also contains 0.6 wt% antioxidant 168 and 0.4 wt% slip agent oleamide, accounting for 0.6 wt% of the total mass of the heat-sealing layer.

[0027] The preparation method is as follows: S1. Accurately weigh 50 parts of metallocene linear low-density polyethylene, 50 parts of ethylene-vinyl acetate copolymer, 510.5 parts of pressure-temperature dual-trigger colorimetric microcapsules, 1680.6 parts of antioxidant, and 0.4 parts of slip agent oleamide. Add all raw materials to a high-speed mixer and mix at 500 rpm for 5 minutes at an ambient temperature of 30°C to obtain a mixture. S2. The mixture is added to a twin-screw extruder. The temperatures of each zone of the extruder are set to 120℃, 125℃, 130℃, 135℃, 140℃, and 145℃ respectively. The die temperature is controlled at 145℃. After the material is melted and plasticized, it is cast to the surface of the cooling roller through the T-die. The temperature of the cooling roller is set to 30℃. The production line speed is controlled at 12m / min. The surface of the cooling roller is pre-engraved with micro-protrusions corresponding to the superhydrophobic micro-nano layer 4 by laser engraving. During the casting process, the structure is directly copied to the heat-sealing layer 3. After cooling and shaping, the heat-sealing layer 3 master roll is obtained. S3. The outer layer 1, barrier layer 2 and heat-sealing layer 3 are bonded together by a solventless bonding process. The solventless adhesive is polyurethane type, the amount of adhesive applied is controlled at 2.3g / m², the bonding temperature is 65℃ and the bonding pressure is 0.4MPa. S4. The composite film roll is sent into the curing chamber and cured at 50°C for 12 hours. Finally, it is cut into finished film rolls with a width of 1000mm by a slitting machine. Example

[0028] This embodiment provides a heat-sealable pharmaceutical packaging film, which is composed of an outer layer 1, a barrier layer 2, and a heat-sealing layer 3 sequentially laminated together. The outer layer 1 is a 10μm thick PA film, the barrier layer 2 is a 6μm thick silicon oxide-coated PET film, and the heat-sealing layer 3 is 20μm thick. A superhydrophobic micro / nano layer 4 is integrally formed on the heat-sealing layer 3. The superhydrophobic micro / nano layer 4 is composed of an array of micro-protrusions with a height of 3μm and a spacing of 15μm, exhibiting a water contact angle of 152° and a roll-off angle of 7°. Pressure-temperature dual-trigger colorimetric microcapsules 5 are uniformly dispersed within the heat-sealing layer 3. The particle size of layer 5 is 0.5 μm. The outer shell is made of food-grade melamine-formaldehyde resin, and the core material is a mixture of colorless crystal violet lactone and p-toluenesulfonic acid. The amount added is 4 wt% of the total mass of the heat-sealing layer. The matrix resin of heat-sealing layer 3 is a blend of metallocene linear low-density polyethylene and ethylene-vinyl acetate copolymer, wherein the vinyl acetate content of ethylene-vinyl acetate copolymer is 16%, and the blending mass ratio is 8:2. Heat-sealing layer 3 also contains 0.1 wt% antioxidant 1076 and 0.05 wt% slip agent stearamide, accounting for 0.1 wt% of the total mass of the heat-sealing layer.

[0029] The preparation method is as follows: S1. Accurately weigh 80 parts of metallocene linear low-density polyethylene, 20 parts of ethylene-vinyl acetate copolymer, 54.2 parts of pressure-temperature dual-trigger colorimetric microcapsules, 0.1 parts of antioxidant 1076, and 0.05 parts of slip agent stearamide. Add all raw materials to a high-speed mixer and mix at 300 rpm for 10 minutes at an ambient temperature of 20°C to obtain a mixture. S2. Add the mixture to a twin-screw extruder. Set the temperatures of each zone of the extruder to 115℃, 118℃, 122℃, 125℃, 128℃, and 125℃ respectively. Control the die temperature at 125℃. After the material is melted and plasticized, it is cast to the surface of the cooling roller through the T-die. Set the temperature of the cooling roller to 15℃. Control the production line speed at 18m / min. The surface of the cooling roller is pre-engraved with micro-protrusions corresponding to the superhydrophobic micro-nano layer 4 using laser engraving. During the casting process, the structure is directly copied onto the heat-sealing layer 3. After cooling and shaping, the heat-sealing layer 3 master roll is obtained. S3. The outer layer 1, barrier layer 2 and heat-sealing layer 3 are bonded together by a solventless bonding process. The solventless adhesive is polyurethane type, the amount of adhesive applied is controlled at 1.2g / m², the bonding temperature is 45℃ and the bonding pressure is 0.2MPa. S4. The composite film roll is sent into the curing chamber and cured at 35°C for 72 hours. Finally, it is cut into finished film rolls with a width of 1000mm by a slitting machine.

[0030] Comparative Example 1: Ordinary low-temperature heat-sealing film The difference between this comparative example and Example 1 is that: the surface of the heat-sealing layer 3 does not have a superhydrophobic micro / nano layer 4, the pressure-temperature dual-trigger colorimetric microcapsules 5 are not added inside, and the heat-sealing layer 3 contains 0.5 wt% of the slip agent erucamide, which accounts for 0.5 wt% of the total mass of the heat-sealing layer. The rest of the structure and preparation method are the same as in Example 1.

[0031] Comparative Example 2: Anti-stick Low-Temperature Heat-Sealing Film with High Content of Slip Agent The difference between this comparative example and Example 1 is that: the surface of the heat-sealing layer 3 does not have a superhydrophobic micro / nano layer 4, the pressure-temperature dual-trigger colorimetric microcapsules 5 are not added inside, and the heat-sealing layer 3 contains 1.2 wt% of the slip agent erucamide, while the rest of the structure and preparation method are the same as in Example 1.

[0032] Comparative Example 3: Low-temperature heat-sealing film with single heat-sealing indicator The difference between this comparative example and Example 1 is that the superhydrophobic micro / nano layer 4 is not provided on the surface of the heat-sealing layer 3, while the rest of the structure and preparation method are the same as in Example 1.

[0033] Comparative Example 4: Single Superhydrophobic Anti-stick Low Temperature Heat-sealing Film The difference between this comparative example and Example 1 is that no pressure-temperature dual-trigger colorimetric microcapsules 5 were added inside the heat-sealing layer 3, while the rest of the structure and preparation method are the same as in Example 1.

[0034] Performance testing methods: 1. Leakage Rate: Take 1000 packaging samples with a specification of 100mm×100mm, and fill each sample with 5g of the corresponding type of drug contents. Heat seal the samples under standard heat sealing conditions of 70℃, 0.2MPa, and 0.3 seconds. Place the heat-sealed samples in a high and low temperature alternating test chamber of -20℃ to 25℃ and perform 50 cycles of hot and cold treatment, with each cycle lasting 4 hours. After the cycle is completed, count the number of samples that leaked and calculate the leakage rate.

[0035] 2. Heat Seal Indication Accuracy: Take 1000 heat-sealed samples and manually observe the color development of the seal to judge the heat seal quality. Uniform color development is acceptable, while partial lack of color development or no color development is unacceptable. Then, test the heat seal strength of each sample according to the method in YBB00152002 "General Rules for Pharmaceutical Composite Films and Bags". A heat seal strength ≥7N / 15mm is acceptable. Count the number of samples whose manual judgment matches the actual test results and calculate the heat seal indication accuracy rate.

[0036] 3. Heat sealing strength: Tested according to the method in YBB00152002 "General Rules for Pharmaceutical Composite Films and Bags", with heat sealing conditions of 70℃, 0.2MPa, 0.3 seconds, and tensile speed of 300mm / min.

[0037] 4. Water contact angle and roll-off angle: The test shall be conducted in accordance with the method in GB / T30693-2014 "Measurement of contact angle between plastic film and water", with deionized water as the test liquid and a droplet volume of 5μL.

[0038] 5. Solvent residue: The test shall be conducted in accordance with the method in YBB00312004 "Determination of Solvent Residue in Packaging Materials" using gas chromatography.

[0039] 6. Accelerated aging test: The sample was placed in a constant temperature and humidity chamber at 40℃ and 90%RH, and removed after 3 months and 6 months respectively to test various performance indicators.

[0040] Test Results and Analysis: Example 1 0.4% 99.6% 9.2 150 0.2 0.3% Example 2 0.6% 99.3% 8.7 145 0.2 0.5% Example 3 0.3% 99.7% 9.5 152 0.1 0.2% Comparative Example 1 13.2% 0% 8.5 102 0.4 11.5% Comparative Example 2 7.8% 0% 7.2 108 1.1 7.3% Comparative Example 3 12.5% 82.3% 9.0 103 0.3 5.2% Comparative Example 4 0.6% 0% 9.1 149 0.2 9.8% Example 1 Water contact angle ° 150 147 143 Example 1 Heat seal strength N / 15mm 9.2 8.9 8.5 Example 1 Heat seal indication accuracy % 99.6 99.5 99.2 Comparative Example 1 Heat seal strength N / 15mm 8.5 7.8 6.9 Comparative Example 2 Heat seal strength N / 15mm 7.2 6.5 5.8 Chinese medicine granules 0.3% 12.8% 99.7% Syrup 0.5% 14.5% 99.3% Topical ointment 0.6% 15.2% 99.1% Vitamin preparations 0.2% 11.6% 99.8% probiotic preparations 0.4% 13.7% 99.5% Antibiotic powder for injection 0.3% 12.3% 99.6% As can be seen from the above test results, the performance indicators of Examples 1-3 of the present invention are significantly better than those of Comparative Examples 1-4. Compared with the single superhydrophobic anti-stick low-temperature heat-sealing film of Comparative Example 4, the present invention reduces the defect rate of finished products from 9.8% to 0.2%-0.5% by adding pressure-temperature dual-trigger color-developing microcapsules 5 inside the heat-sealing layer 3, completely solving the problem that the single anti-stick film cannot intuitively judge the heat-sealing quality, and avoiding the entry of sealing defects caused by process fluctuations or equipment wear into the market. Compared with the single heat-sealing indicator low-temperature heat-sealing film of Comparative Example 3, the present invention reduces the leakage rate of trapped material from 12.5% ​​to 0.3%-0.6% by setting a superhydrophobic micro-nano layer 4 on the heat-sealing layer 3, while increasing the heat-sealing indicator accuracy from 82.3% to 99.3%-99.7%. This is because the superhydrophobic micro-nano layer 4 can effectively prevent the contents from adhering to the sealing surface, avoid insufficient local pressure caused by trapped material, and thus ensure that the microcapsules 5 in all heat-sealing areas can be reliably triggered for color development, eliminating the false negative problem. The two technical features of this invention produce a significant synergistic effect; the superhydrophobic micro / nano layer 4 not only solves the problem of material trapping and leakage, but also provides a reliable working environment for the heat seal indication function; while the pressure-temperature dual-trigger colorimetric microcapsule 5 not only solves the problem of invisible heat seal quality, but also can detect sealing failure caused by wear of the superhydrophobic micro / nano layer 4 in a timely manner; the two work together to build a complete quality assurance system, achieving simultaneous improvement in anti-stick performance and heat seal quality indication performance; Compared with the anti-stick low-temperature heat-sealing film of Comparative Example 2 with a high content of slip agent, the present invention does not require the addition of a high content of migratory slip agent, and the solvent residue is lower, only 0.1-0.2 mg / m², which is far below the limit of ≤5.0 mg / m² specified in YBB00152002 standard, resulting in higher drug safety. At the same time, the heat-sealing strength of the present invention is higher and the long-term stability is better. After aging for 6 months under 40℃ / 90%RH conditions, the heat-sealing strength can still be maintained above 8.5 N / 15 mm, while the heat-sealing strength of Comparative Example 2 has dropped to 5.8 N / 15 mm. The preparation process of this invention is simple and can be directly produced using existing casting and lamination equipment. Only one cooling roller with microstructures engraved on its surface needs to be replaced. The equipment modification cost is only 4,000-6,000 yuan, which is far lower than the 500,000-800,000 yuan of traditional online visual inspection equipment. The production efficiency is completely equivalent to that of ordinary heat-sealing film, making it suitable for large-scale industrial application. In summary, the heat-sealing pharmaceutical packaging film provided by this invention can effectively prevent the contents from adhering, achieve visualization of heat-sealing quality, is safe and non-toxic, has a simple process, low cost, and has excellent comprehensive performance and broad market application prospects.

[0041] Preferably, the outer layer 1 is a PET, BOPP or PA film with a thickness of 10-25μm; the barrier layer 2 is an aluminum foil, alumina-plated PET, silicon oxide-plated PET or EVOH film with a thickness of 6-15μm.

[0042] In this implementation case, the outer layer 1 can be selected from different types of film materials according to printing requirements and mechanical performance requirements, and the barrier layer 2 can be selected from the corresponding barrier materials according to the drug's requirements for blocking oxygen and water vapor. The different materials are bonded together by solvent-free composite adhesive. The material types of the outer layer 1 and the barrier layer 2 can be flexibly combined according to the packaging requirements of different drugs. For example, aluminum foil can be selected as the barrier layer 2 for injectable drugs that need to be stored for a long time, and aluminum oxide coated with PET can be selected as the barrier layer 2 for cost-sensitive oral drugs. This multi-material design can cover the performance requirements of most pharmaceutical packaging on the market, avoiding the problem of limited protection caused by limiting a single material, while ensuring that the product has the best mechanical and barrier properties in different application scenarios.

[0043] The preferred heat-sealing layer 3 matrix is ​​a blend of metallocene linear low-density polyethylene and ethylene-vinyl acetate copolymer, wherein the ethylene-vinyl acetate copolymer has a vinyl acetate content of 16-24% and a blending mass ratio of 8:2-5:5.

[0044] In this embodiment, the matrix of heat-sealing layer 3 is prepared by blending metallocene linear low-density polyethylene with ethylene-vinyl acetate copolymer. During blending, the two resins are first added to a high-speed mixer in a set ratio and mixed evenly, and then fed into a twin-screw extruder for melt blending and granulation. The vinyl acetate content of the ethylene-vinyl acetate copolymer and the blending ratio of the two resins can be adjusted according to the target heat sealing temperature requirements. The higher the vinyl acetate content, the lower the heat sealing temperature of the blend. At the same time, a small amount of thermoplastic elastomer can be added to further improve the low-temperature toughness of the heat sealing layer 3. This matrix formulation has been validated through extensive industrial production, demonstrating excellent low-temperature heat-sealing performance while ensuring good mechanical strength, thus balancing the product's processing and performance characteristics.

[0045] The preferred superhydrophobic micro / nano layer 4 has a water contact angle ≥145° and a roll-off angle ≤12°, and is composed of an array of micro-protrusions with a height of 3-12μm and a spacing of 15-35μm.

[0046] In this implementation case, the superhydrophobic micro-nano layer 4 is composed of a uniformly distributed array of micro-protrusions. The corresponding micro-protrusion structure is engraved on the surface of the cooling roller by laser engraving process, and then the structure is copied onto the heat-sealing surface of the heat-sealing layer 3 by the casting film process. The shape and arrangement of the micro-protrusions can be adjusted according to the anti-sticking requirements of different contents. For example, a denser array of micro-protrusions can be used for powdered contents, while a hemispherical micro-protrusion structure can be used for liquid contents. This parameter range balances the superhydrophobic and anti-stick properties with the difficulty of industrial-scale preparation, enabling stable mass production under existing equipment conditions while ensuring anti-adhesion performance against various contents.

[0047] The preferred pressure-temperature dual-trigger colorimetric microcapsules have a particle size of 0.5-4μm, a shell made of food-grade polyurea or melamine-formaldehyde resin, and a core material made of a mixture of colorless crystal violet lactone and an acidic colorimetric agent. The amount of pressure-temperature dual-trigger colorimetric microcapsules added is 4-9wt% of the total mass of the heat-sealing layer.

[0048] In this embodiment, the pressure-temperature dual-trigger colorimetric microcapsules 5 are prepared by in-situ polymerization. First, the core material components are emulsified and dispersed in the aqueous phase, and then monomers are added to carry out a polymerization reaction to form the shell. After washing and drying, the prepared microcapsules 5 are mixed with the matrix resin of the heat-sealing layer 3. The color developer components in the core material can be changed according to different color requirements to achieve different color development effects such as blue, red, and green. At the same time, the shell thickness of the microcapsule 5 can be adjusted to change the triggering pressure and temperature threshold. The food-grade shell material ensures that the microcapsules 5 will not contaminate the drug, and the appropriate particle size range ensures that the microcapsules 5 are uniformly dispersed in the matrix resin, while being reliably triggered to rupture during the heat sealing process.

[0049] The preferred thickness of the heat-sealing layer is 20-40 μm, and the heat-sealing layer also contains 0.1-0.6 wt% antioxidant and 0.05-0.4 wt% slip agent, accounting for 0.1-0.6 wt% of the total mass of the heat-sealing layer.

[0050] In this implementation case, the thickness of the heat-sealing layer 3 is adjusted according to the heat-sealing strength requirements and processing performance. The antioxidant and slip agent are added together with the matrix resin and microcapsules 5 in the high-speed mixer during the raw material mixing stage and mixed evenly. The amount of additives can be adjusted according to different processing equipment and production environment. For example, the amount of antioxidants can be increased appropriately in high temperature and high humidity environments, and the amount of slip agent can be increased appropriately on high-speed production lines. This thickness range and additive dosage ensure that the heat-sealing layer 3 has sufficient heat-sealing strength and good processing performance, prevents the resin from undergoing thermal oxidative degradation during processing, and improves the opening and winding performance of the film.

[0051] In preferred step S1, mixing is performed at 300-500 rpm for 5-10 minutes; in step S2, the extrusion temperature is 115-145℃ and the cooling roller temperature is 15-30℃; in step S3, the coating amount is 1.2-2.3 g / m² and the compounding temperature is 45-65℃; in step S4, curing is performed at 35-50℃ for 12-72 hours.

[0052] In this implementation case, during the preparation process, the speed and mixing time of the high-speed mixer are adjusted according to the dispersion effect of the raw materials, the temperature of each zone of the twin-screw extruder is set according to the melting characteristics of the resin, and the temperature of the cooling roller is controlled according to the replication effect of the microstructure. A multi-layer structure containing a heat-sealing layer 3, a transition layer and a barrier layer 2 can be prepared simultaneously using a three-layer co-extrusion casting process, reducing subsequent composite processes and improving production efficiency; All process parameters have been verified in industrial production to ensure the stability and consistency of product quality. At the same time, the selectable range avoids product quality problems caused by equipment differences or environmental fluctuations.

[0053] The preferred heat-sealing pressure is 0.15-0.35 MPa, and the heat-sealing time is 0.2-0.6 seconds. The drugs include traditional Chinese medicine granules, syrups, ointments, vitamin preparations, probiotic preparations, and antibiotic preparations.

[0054] In this implementation case, when applying low-temperature heat sealing for pharmaceuticals, the heat sealing pressure and heat sealing time are adjusted according to different packaging equipment and packaging speeds. For high-speed packaging lines, the heat sealing pressure can be appropriately increased and the heat sealing time shortened, while for low-speed packaging lines, the heat sealing pressure can be appropriately decreased and the heat sealing time extended. It is compatible with all mainstream intermittent and continuous heat sealing packaging equipment on the market, without the need for large-scale modification of existing equipment. The range of process parameters can ensure stable and reliable heat sealing effect under different production conditions, with an extremely wide process window and strong equipment adaptability.

[0055] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. A heat-sealable pharmaceutical packaging film, characterized in that: It includes an outer layer (1), a barrier layer (2) and a heat-sealing layer (3) that are sequentially composited. The heat-sealing layer (3) has a superhydrophobic micro / nano layer (4) on its heat-sealing surface. Pressure-temperature dual-trigger color-developing microcapsules (5) are uniformly dispersed inside the heat-sealing layer (3).

2. The heat-sealable pharmaceutical packaging film according to claim 1, characterized in that: The outer layer (1) is a PET, BOPP or PA film with a thickness of 10-25μm; the barrier layer (2) is an aluminum foil, alumina-plated PET, silicon oxide-plated PET or EVOH film with a thickness of 6-15μm.

3. The heat-sealable pharmaceutical packaging film according to claim 1, characterized in that: The heat-sealing layer (3) matrix is ​​a blend of metallocene linear low-density polyethylene and ethylene-vinyl acetate copolymer, wherein the ethylene-vinyl acetate copolymer has a vinyl acetate content of 16-24% and a blending mass ratio of 8:2-5:

5.

4. The heat-sealable pharmaceutical packaging film according to claim 1, characterized in that: The superhydrophobic micro / nano layer (4) has a water contact angle ≥145° and a roll-off angle ≤12°, and is composed of an array of micro-protrusions with a height of 3-12μm and a spacing of 15-35μm.

5. The heat-sealable pharmaceutical packaging film according to claim 1, characterized in that: The pressure-temperature dual-trigger colorimetric microcapsules have a particle size of 0.5-4μm, a shell made of food-grade polyurea or melamine-formaldehyde resin, and a core material made of a mixture of colorless crystal violet lactone and an acidic colorimetric agent. The amount of pressure-temperature dual-trigger colorimetric microcapsules added is 4-9wt% of the total mass of the heat-sealing layer.

6. The heat-sealable pharmaceutical packaging film according to claim 1, characterized in that: The heat-sealing layer has a thickness of 20-40 μm and also contains 0.1-0.6 wt% antioxidant and 0.05-0.4 wt% slip agent, accounting for 0.1-0.6 wt% of the total mass of the heat-sealing layer.

7. A method for preparing a heat-sealable pharmaceutical packaging film, comprising the heat-sealable pharmaceutical packaging film as described in any one of claims 1-6, characterized in that, Includes the following steps: S1. Mix the heat-sealing layer (3) raw materials evenly; S2, melt extrusion casting to form a film, and at the same time, the structure is replicated onto the heat-sealing layer (3) heat-sealing surface by a cooling roller with the superhydrophobic micro-nano layer (4); S3. Solvent-free composite of the outer layer (1), the barrier layer (2) and the heat-sealing layer (3); S4. After maturation, the product is cut into pieces.

8. The method for preparing a heat-sealable pharmaceutical packaging film according to claim 7, characterized in that: In step S1, mix at 300-500 rpm for 5-10 minutes; In step S2, the extrusion temperature is 115-145℃, and the cooling roller temperature is 15-30℃; In step S3, the amount of adhesive applied is 1.2-2.3 g / m², and the lamination temperature is 45-65℃; In step S4, the product is aged at 35-50℃ for 12-72 hours.

9. The application of a heat-sealable pharmaceutical packaging film in low-temperature heat sealing of pharmaceuticals, comprising the heat-sealable pharmaceutical packaging film as described in any one of claims 1-6, characterized in that: The heat sealing temperature is 68-78℃.

10. The application of the heat-sealable pharmaceutical packaging film according to claim 9 in low-temperature heat sealing of pharmaceuticals, characterized in that: The heat sealing pressure is 0.15-0.35 MPa, and the heat sealing time is 0.2-0.6 seconds. The medicines include traditional Chinese medicine granules, syrups, ointments, vitamin preparations, probiotic preparations, and antibiotic preparations.

Images