Low-temperature heat-sealed medicinal packaging composite film

Abstract

The invention relates to a low-temperature heat-sealing medicinal packaging composite film, and belongs to the technical field of medicinal packaging. The invention provides a low-temperature heat-sealed medicinal packaging composite film which is prepared by laminating a mussel mucin inner layer, a polyester film middle layer and an aluminum foil outer layer and then drying in a gradient heating manner, the aluminum foil outer layer of the prepared medicinal packaging composite film resists oxygen and moisture, and the polyester film middle layer provides mechanical support. And the inner layer of the mussel mucin is in direct contact with the medicine, so that the prepared medicinal packaging composite film can realize heat sealing at a relatively low temperature, and the medicine is effectively preserved.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical packaging, and relates to a pharmaceutical packaging composite film with low-temperature heat sealing. Background Art

[0002] Pharmaceutical packaging films are usually composed of aluminum foil and polymer plastic films, and are widely used in the packaging and protection of drugs, aiming to avoid the adverse effects of the external environment on drugs, improve the stability of drugs, and extend the shelf life. Polyester film is one of the most commonly used packaging films at present. In actual application, the heat-sealing temperature of polyester film is relatively high. For special packaging items such as drugs, in order to avoid the degradation of drug thermosensitive components caused by traditional heat sealing above 130°C, there is still a need to improve the existing polyester film pharmaceutical packaging film. Summary of the Invention

[0003] The purpose of the present invention is to provide a pharmaceutical packaging composite film with low-temperature heat sealing. The present invention prepares a pharmaceutical packaging film with a multi-layer composite structure, where the outer aluminum foil layer blocks oxygen and moisture, the middle polyester film layer provides mechanical support, and the inner mussel adhesive protein layer directly contacts the drug. The prepared pharmaceutical packaging composite film can achieve heat sealing at a lower temperature and effectively preserve the drug.

[0004] The purpose of the present invention can be achieved by the following technical solutions:

[0005] A pharmaceutical packaging composite film with low-temperature heat sealing, the pharmaceutical packaging composite film includes a mussel adhesive protein inner layer, a polyester film middle layer, and an aluminum foil outer layer stacked in sequence;

[0006] Among them, the way to achieve the stacking is that the mussel adhesive protein inner layer, the polyester film middle layer, and the aluminum foil outer layer are dried by a gradient heating method.

[0007] Further, the thickness of the mussel adhesive protein inner layer is 6-8 μm; the thickness of the polyester film middle layer is 10-14 μm; the thickness of the aluminum foil outer layer is 7-9 μm.

[0008] Further, the adhesive used to achieve the stacking is waterborne polyurethane, and the bonding pressure is 0.3-0.5 MPa; the gradient heating method for drying means that it is first cured at 55-65°C for 11-13 h, and then heated to 70-80°C and maintained for 5-7 h.

[0009] Further, the preparation method of the mussel adhesive protein inner layer includes the following steps:

[0010] Step A1: Mix the modified mussel adhesive protein powder, aqueous polyurethane, tributyl acetylcitrate, nano-silica with an average particle size of 10 - 30 nm, vitamin E, and deionized water according to the mass ratio of 1 - 1.5:0.5 - 0.8:0.2 - 0.3:0.1 - 0.2:0.04 - 0.06:8.1 - 8.5. Set the ultrasonic frequency to 30 - 50 kHz, the ultrasonic power to 100 - 200 W, and ultrasonic for 15 - 25 min, then coat it on the surface of the polyester film with a coating thickness of 1.2 - 1.8 μm, and then dry it at 60 °C to obtain the mussel adhesive protein inner layer.

[0011] Further, the preparation method of the modified mussel adhesive protein powder described in Step A1 includes the following steps:

[0012] Step B1: Add mussel adhesive protein into PBS buffer solution, then add acrylic acid and potassium persulfate, and at the same time, dropwise add hydrochloric acid to adjust the pH to 4.8 - 5.2, and water bath at 58 - 62 °C for 3 - 4 h to obtain a primary product;

[0013] Step B2: Add genipin accounting for 0.5 - 1 wt% of the mass of the primary product to the primary product, let it stand at room temperature for 10 - 14 h, dialyze to remove unreacted monomers, and freeze-dry to obtain the modified mussel adhesive protein powder.

[0014] Further, the mass ratio of the mussel adhesive protein, acrylic acid, potassium persulfate, and PBS buffer solution described in Step B1 is 1:0.03 - 0.07:0.004 - 0.006:10 - 12; the concentration of the PBS buffer solution is 0.01 - 0.02 mol / L; the concentration of the hydrochloric acid is 0.1 - 0.2 mol / L.

[0015] Further, the polyester film described in Step A1 is treated by plasma. The specific operation is to introduce argon and oxygen according to a ratio of 4:1, set the power to 200 - 300 W, and perform plasma treatment for 86 - 94 s.

[0016] The beneficial effects of the present invention:

[0017] (1) The present invention provides a multi-layer composite structure medicinal packaging film. The aluminum foil outer layer has oxygen and moisture barrier properties, the polyester film intermediate layer provides mechanical support, and the mussel adhesive protein inner layer directly contacts the drug. The prepared medicinal packaging composite film can be heat-sealed at a lower temperature and effectively preserve the drug.

[0018] (2) In the present invention, the hydrophobic surface of the mussel adhesive protein inner layer can reduce the moisture absorption of drugs. The mussel adhesive protein itself has good adhesiveness, and the mussel adhesive protein contains dopa residues. The dopa residues have phenolic hydroxyl groups that may form molecular hydrogen bonds with the carboxyl groups on the polyacrylic acid formed by the polymerization of acrylic acid monomers to form a complex, thereby introducing flexible chain ends on the protein molecular chain. Combined with the plasticization of tributyl acetylcitrate, the temperature requirement for heat sealing is reduced, promoting interfacial diffusion and flow to achieve an adhesion effect. On this basis, genipin is used to react with the mussel adhesive protein to form a heat-resistant crosslinked network, inhibiting the movement of protein molecular chains and reducing the creep risk during use. In addition, a gradient heating drying process is adopted during the preparation process to ensure the curing of the adhesive while avoiding the long-term high-temperature exposure of the mussel adhesive protein during the early preparation stage. Detailed implementation manners

[0019] To further elaborate on the technical means and effects adopted by the present invention to achieve the predetermined invention purpose, the following, in combination with embodiments, details the specific implementation manners, structures, features, and their effects according to the present invention as follows.

[0020] The mussel adhesive proteins in all the embodiments and comparative examples of the present invention are directly purchased from the market, all purchased from Hubei Langbowan Biopharmaceutical Co., Ltd.; acrylic acid, potassium persulfate, PBS buffer solution, hydrochloric acid, and genipin are all directly purchased from the market, all purchased from Sigma-Aldrich (Shanghai) Trading Co., Ltd.; waterborne polyurethane is all directly purchased from the market, all purchased from Anhui Femtosecond Chemical Co., Ltd.; tributyl acetylcitrate is all directly purchased from the market, all purchased from Weifang Hanghao New Material Technology Co., Ltd.; nano-silica is all directly purchased from the market, all purchased from Hubei Xinyuhong Biopharmaceutical Technology Co., Ltd.; vitamin E is all directly purchased from the market, all purchased from Jiangsu Huace Biotechnology Co., Ltd.; aluminum foil is all directly purchased from the market, all purchased from Gongyi Boyu Aluminum Materials Sales Co., Ltd.

[0021] Example 1

[0022] A pharmaceutical packaging composite film with low-temperature heat sealing. The pharmaceutical packaging composite film of this example includes a mussel adhesive protein inner layer, a polyester film intermediate layer, and an aluminum foil outer layer laminated in sequence;

[0023] Among them, the way to achieve the lamination is that the mussel adhesive protein inner layer, the polyester film intermediate layer, and the aluminum foil outer layer are dried by a gradient heating method.

[0024] The thickness of the mussel adhesive protein inner layer in this example is 6 μm; the thickness of the polyester film intermediate layer is 10 μm; the thickness of the aluminum foil outer layer is 7 μm.

[0025] The adhesive used to achieve the lamination in this embodiment is aqueous polyurethane, and the bonding pressure is 0.3 MPa; the gradient heating drying method means that it is first cured at 55 °C for 11 h, and then heated to 70 °C and maintained for 5 h.

[0026] The preparation method of the mussel adhesive protein inner layer in this embodiment includes the following steps:

[0027] Step A1: After mixing the modified mussel adhesive protein powder, aqueous polyurethane, tributyl acetylcitrate, nano-silica with an average particle size of 10 nm, vitamin E, and deionized water according to a mass ratio of 1:0.5:0.2:0.1:0.04:8.1, set the ultrasonic frequency to 30 kHz, the ultrasonic power to 100 W, coat it on the surface of the polyester film after ultrasonic treatment for 15 min, with a coating thickness of 1.2 μm, and then dry it at 60 °C to obtain the mussel adhesive protein inner layer.

[0028] The preparation method of the modified mussel adhesive protein powder in step A1 of this embodiment includes the following steps:

[0029] Step B1: Add mussel adhesive protein to PBS buffer solution, then add acrylic acid and potassium persulfate, and at the same time dropwise add hydrochloric acid to adjust the pH to 4.8, and carry out a water bath at 58 °C for 34 h to obtain a primary product;

[0030] Step B2: Add 0.5 wt% of genipin based on the mass of the primary product to the primary product, let it stand at room temperature for 10 h, dialyze to remove unreacted monomers, and freeze-dry to obtain the modified mussel adhesive protein powder.

[0031] In step B1 of this embodiment, the mass ratio of mussel adhesive protein, acrylic acid, potassium persulfate, and PBS buffer solution is 1:0.03:0.004:10; the concentration of PBS buffer solution is 0.01 mol / L; the concentration of hydrochloric acid is 0.1 mol / L.

[0032] In step A1 of this embodiment, the polyester film is treated by plasma. The specific operation is to introduce argon and oxygen according to a ratio of 4:1, set the power to 200 W, and carry out plasma treatment for 86 s.

[0033] Example 2

[0034] A pharmaceutical packaging composite film with low-temperature heat sealing. The pharmaceutical packaging composite film in this embodiment includes a mussel adhesive protein inner layer, a polyester film intermediate layer, and an aluminum foil outer layer laminated in sequence;

[0035] Among them, the way to achieve the lamination is that the mussel adhesive protein inner layer, the polyester film intermediate layer, and the aluminum foil outer layer are dried by a gradient heating method.

[0036] The thickness of the mussel adhesive protein inner layer in this embodiment is 6.7 μm; the thickness of the polyester film intermediate layer is 11 μm; the thickness of the aluminum foil outer layer is 7.5 μm.

[0037] The adhesive used for the lamination in this embodiment is waterborne polyurethane, and the bonding pressure is 0.35 MPa; the drying by gradient temperature rise means that it is first cured at 57 °C for 11.6 h, and then the temperature is raised to 73 °C and maintained for 5.5 h.

[0038] The preparation method of the mussel adhesive protein inner layer in this embodiment includes the following steps:

[0039] Step A1: After mixing the modified mussel adhesive protein powder, waterborne polyurethane, tributyl acetylcitrate, nano-silica with an average particle size of 15 nm, vitamin E, and deionized water according to a mass ratio of 1.2:0.6:0.23:0.12:0.04:8.2, set the ultrasonic frequency to 35 kHz, the ultrasonic power to 120 W, coat it on the surface of the polyester film after ultrasonic treatment for 18 min, with a coating thickness of 1.4 μm, and then dry it at 60 °C to obtain the mussel adhesive protein inner layer.

[0040] The preparation method of the modified mussel adhesive protein powder in step A1 of this embodiment includes the following steps:

[0041] Step B1: Add mussel adhesive protein to PBS buffer solution, then add acrylic acid and potassium persulfate, and simultaneously add hydrochloric acid dropwise to adjust the pH to 4.9, and carry out a water bath at 59 °C for 3.2 h to obtain a primary product;

[0042] Step B2: Add genipin accounting for 0.6 wt% of the mass of the primary product to the primary product, let it stand at room temperature for 11 h, dialyze to remove unreacted monomers, and freeze-dry to obtain the modified mussel adhesive protein powder.

[0043] In step B1 of this embodiment, the mass ratio of mussel adhesive protein, acrylic acid, potassium persulfate, and PBS buffer solution is 1:0.04:0.004:10.8; the concentration of PBS buffer solution is 0.01 mol / L; the concentration of hydrochloric acid is 0.1 mol / L.

[0044] In this embodiment, the polyester film in step A1 is treated by plasma. The specific operation is to introduce argon and oxygen according to a ratio of 4:1, set the power to 220 W, and carry out plasma treatment for 88 s.

[0045] Example 3

[0046] A pharmaceutical packaging composite film with low-temperature heat sealing. The pharmaceutical packaging composite film in this embodiment includes a mussel adhesive protein inner layer, a polyester film intermediate layer, and an aluminum foil outer layer laminated in sequence;

[0047] Among them, the way to achieve the lamination is to dry the mussel adhesive protein inner layer, the polyester film intermediate layer, and the aluminum foil outer layer by gradient heating.

[0048] In this embodiment, the thickness of the mussel adhesive protein inner layer is 7 μm; the thickness of the polyester film intermediate layer is 12 μm; the thickness of the aluminum foil outer layer is 8 μm.

[0049] The adhesive used to achieve the lamination in this embodiment is waterborne polyurethane, and the bonding pressure is 0.4 MPa; the gradient heating drying means that it is first cured at 60 °C for 12 h, and then heated to 75 °C and maintained for 6 h.

[0050] The preparation method of the mussel adhesive protein inner layer in this embodiment includes the following steps:

[0051] Step A1: Mix the modified mussel adhesive protein powder, waterborne polyurethane, tributyl acetylcitrate, nano-silica with an average particle size of 20 nm, vitamin E, and deionized water according to a mass ratio of 1.25:0.65:0.25:0.15:0.05:8.3. Then set the ultrasonic frequency to 40 kHz, the ultrasonic power to 150 W, and ultrasonicate for 20 min. After that, coat it on the surface of the polyester film with a coating thickness of 1.5 μm, and then dry it at 60 °C to obtain the mussel adhesive protein inner layer.

[0052] The preparation method of the modified mussel adhesive protein powder in step A1 of this embodiment includes the following steps:

[0053] Step B1: Add mussel adhesive protein to PBS buffer solution, then add acrylic acid and potassium persulfate, and at the same time add hydrochloric acid dropwise to adjust the pH to 5, and carry out a water bath at 60 °C for 3.5 h to obtain a primary product;

[0054] Step B2: Add genipin accounting for 0.75 wt% of the mass of the primary product to the primary product, let it stand at room temperature for 12 h, dialyze to remove unreacted monomers, and freeze-dry to obtain the modified mussel adhesive protein powder.

[0055] In step B1 of this embodiment, the mass ratio of mussel adhesive protein, acrylic acid, potassium persulfate, and PBS buffer solution is 1:0.05:0.005:11; the concentration of PBS buffer solution is 0.015 mol / L; the concentration of hydrochloric acid is 0.15 mol / L.

[0056] In this embodiment, the polyester film in step A1 is treated by plasma. The specific operation is to introduce argon and oxygen according to a ratio of 4:1, set the power to 250 W, and carry out plasma treatment for 90 s.

[0057] Example 4

[0058] A pharmaceutical packaging composite film with low-temperature heat sealing. The pharmaceutical packaging composite film of this embodiment includes a mussel adhesive protein inner layer, a polyester film intermediate layer, and an aluminum foil outer layer that are laminated in sequence;

[0059] Among them, the way to achieve the lamination is that the mussel adhesive protein inner layer, the polyester film intermediate layer, and the aluminum foil outer layer are dried by a gradient heating method.

[0060] In this embodiment, the thickness of the mussel adhesive protein inner layer is 7.5 μm; the thickness of the polyester film intermediate layer is 13 μm; the thickness of the aluminum foil outer layer is 8.2 μm.

[0061] The adhesive used to achieve the lamination in this embodiment is waterborne polyurethane, and the bonding pressure is 0.45 MPa; the gradient heating method for drying means that it is first cured at 62 °C for 12.6 h, and then heated to 77 °C and maintained for 6.5 h.

[0062] The preparation method of the mussel adhesive protein inner layer in this embodiment includes the following steps:

[0063] Step A1: After mixing the modified mussel adhesive protein powder, waterborne polyurethane, tributyl acetyl citrate, nano-silica with an average particle size of 25 nm, vitamin E, and deionized water according to a mass ratio of 1.4:0.72:0.28:0.17:0.06:8.4, set the ultrasonic frequency to 45 kHz, the ultrasonic power to 180 W, ultrasonic for 22 min, then coat it on the surface of the polyester film, with a coating thickness of 1.6 μm, and then dry it at 60 °C to obtain the mussel adhesive protein inner layer.

[0064] The preparation method of the modified mussel adhesive protein powder in step A1 of this embodiment includes the following steps:

[0065] Step B1: Add mussel adhesive protein to PBS buffer solution, then add acrylic acid and potassium persulfate, and at the same time dropwise add hydrochloric acid to adjust the pH to 5.1, and carry out a water bath at 61 °C for 3.6 h to obtain a primary product;

[0066] Step B2: Add genipin accounting for 0.87 wt% of the mass of the primary product to the primary product, let it stand at room temperature for 13 h, dialyze to remove unreacted monomers, and freeze-dry to obtain the modified mussel adhesive protein powder.

[0067] In step B1 of this embodiment, the mass ratio of mussel adhesive protein, acrylic acid, potassium persulfate, and PBS buffer solution is 1:0.06:0.006:11.7; the concentration of PBS buffer solution is 0.02 mol / L; the concentration of hydrochloric acid is 0.2 mol / L.

[0068] In this embodiment, the polyester film in step A1 is treated by plasma. The specific operation is to introduce argon and oxygen according to a ratio of 4:1, set the power to 280 W, and carry out plasma treatment for 92 s.

[0069] Example 5

[0070] A pharmaceutical packaging composite film with low-temperature heat sealing. The pharmaceutical packaging composite film of this example includes a mussel adhesive protein inner layer, a polyester film intermediate layer, and an aluminum foil outer layer that are laminated in sequence.

[0071] Among them, the way to achieve the lamination is that the mussel adhesive protein inner layer, the polyester film intermediate layer, and the aluminum foil outer layer are dried by a gradient heating method.

[0072] In this example, the thickness of the mussel adhesive protein inner layer is 8 μm; the thickness of the polyester film intermediate layer is 14 μm; the thickness of the aluminum foil outer layer is 9 μm.

[0073] The adhesive used to achieve the lamination in this example is waterborne polyurethane, and the bonding pressure is 0.5 MPa; the gradient heating method for drying means that it is first cured at 65 °C for 13 h, and then the temperature is raised to 80 °C and maintained for 7 h.

[0074] The preparation method of the mussel adhesive protein inner layer in this example includes the following steps:

[0075] Step A1: After mixing the modified mussel adhesive protein powder, waterborne polyurethane, tributyl acetyl citrate, nano-silica with an average particle size of 30 nm, vitamin E, and deionized water according to a mass ratio of 1.5:0.8:0.3:0.2:0.06:8.5, set the ultrasonic frequency to 50 kHz, the ultrasonic power to 200 W, ultrasonic for 25 min, then coat it on the surface of the polyester film, the coating thickness is 1.8 μm, and then dry it at 60 °C to obtain the mussel adhesive protein inner layer.

[0076] The preparation method of the modified mussel adhesive protein powder in step A1 of this example includes the following steps:

[0077] Step B1: Add mussel adhesive protein to PBS buffer solution, then add acrylic acid and potassium persulfate, and at the same time dropwise add hydrochloric acid to adjust the pH to 5.2, and carry out a water bath at 62 °C for 4 h to obtain a primary product;

[0078] Step B2: Add 1 wt% of genipin to the primary product, let it stand at room temperature for 14 h, dialyze to remove unreacted monomers, and freeze-dry to obtain the modified mussel adhesive protein powder.

[0079] In step B1 of this example, the mass ratio of mussel adhesive protein, acrylic acid, potassium persulfate, and PBS buffer solution is 1:0.07:0.006:12; the concentration of PBS buffer solution is 0.02 mol / L; the concentration of hydrochloric acid is 0.2 mol / L.

[0080] In this embodiment, the polyester film in step A1 is treated by plasma. The specific operation is to introduce argon and oxygen in a ratio of 4:1, set the power to 300 W, and perform plasma treatment for 94 s.

[0081] Example 6

[0082] On the basis of Example 3, the mussel adhesive protein powder is not modified, and other conditions are the same as those in Example 3.

[0083] Example 7

[0084] On the basis of Example 3, tributyl acetylcitrate in the preparation of the mussel adhesive protein inner layer is removed and replaced with deionized water of equal weight, and other conditions are the same as those in Example 3.

[0085] Example 8

[0086] On the basis of Example 3, nano-silica in the preparation of the mussel adhesive protein inner layer is removed and replaced with deionized water of equal weight, and other conditions are the same as those in Example 3.

[0087] Comparative Example 1

[0088] On the basis of Example 3, while keeping other conditions the same, the preparation method of the modified mussel adhesive protein powder is changed to the following steps:

[0089] Step B1: Add mussel adhesive protein into PBS buffer solution, then add acrylic acid and potassium persulfate, and simultaneously add hydrochloric acid to adjust the pH to 5. Heat in a water bath at 60 °C for 3.5 h, dialyze to remove unreacted monomers, and freeze-dry to obtain the modified mussel adhesive protein powder.

[0090] Comparative Example 2

[0091] On the basis of Example 3, the drying step of gradient temperature increase is changed to curing at 75 °C for 18 h, and other conditions are the same as those in Example 3.

[0092] Comparative Example 3

[0093] On the basis of Example 3, the polyester film in step A1 is not treated by plasma, and other conditions are the same as those in Example 3.

[0094] Comparative Example 4

[0095] On the basis of Example 3, while keeping other conditions the same, the operation of treating the polyester film in step A1 by plasma is changed to introducing argon, setting the power to 250 W, and performing plasma treatment for 90 s.

[0096] Comparative Example 5

[0097] On the basis of Example 3, while keeping other conditions the same, the operation of plasma treating the polyester film in step A1 was changed to introducing argon and oxygen in a ratio of 1:1, setting the power to 250 W, and performing plasma treatment for 90 s.

[0098] Taking the pharmaceutical packaging composite films prepared in Examples 1 - 8 and Comparative Examples 1 - 5 as samples, the heat seal strength obtained by heat sealing the samples at 180 kPa and 100 °C for 1 s was tested. Five parallel tests were conducted for each group of samples, and the average value was recorded as shown in Table 1 below.

[0099] Table 1

[0100]

[0101]

[0102] As can be seen from Table 1, the pharmaceutical packaging composite film prepared by the present invention can still obtain good heat seal strength at a relatively low heat seal temperature, and can reduce the influence of high temperature on the drug stability during actual application.

[0103] The above are only the preferred embodiments of the present invention, and do not impose any form of limitation on the present invention. Although the present invention has been disclosed as above with preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or equivalent variations within the scope of the technical solution of the present invention. However, any indirect modification, equivalent variation and modification made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A low-temperature heat-sealed composite film for pharmaceutical packaging, characterized in that: The medicinal packaging composite film comprises a mussel mucin inner layer, a polyester film middle layer and an aluminum foil outer layer which are stacked in sequence; The stacking is achieved by drying the inner layer of mussel mucin, the middle layer of polyester film and the outer layer of aluminum foil in a gradient temperature rising manner.

2. The low-temperature heat-sealed composite film for pharmaceutical packaging according to claim 1, characterized in that: The thickness of the inner layer of mussel mucin is 6-8 μm; the thickness of the middle layer of polyester film is 10-14 μm; and the thickness of the outer layer of aluminum foil is 7-9 μm.

3. The low-temperature heat-sealed composite film for pharmaceutical packaging according to claim 1, characterized in that: The adhesive used to achieve the lamination is water-based polyurethane, and the bonding pressure is 0.3-0.5MPa; the gradient temperature drying method means first curing at 55-65°C for 11-13h, and then heating to 70-80°C and maintaining for 5-7h.

4. The low-temperature heat-sealed composite film for pharmaceutical packaging according to claim 1, characterized in that: The method for preparing the mussel mucin inner layer comprises the following steps: Step A1, the modified mussel mucin powder, water-based polyurethane, acetylcitrate tributyl, nano-silicon dioxide with an average particle size of 10-30 nm, vitamin E, and deionized water are mixed in a mass ratio of 1-1.5: 0.5-0.8: 0.2-0.3: 0.1-0.2: 0.04-0.06: 8.1-8.5, the ultrasonic frequency is set to 30-50 kHz, the ultrasonic power is 100-200 W, and the ultrasonic is applied to the surface of the polyester film after 15-25 minutes, the coating thickness is 1.2-1.8 μm, and then dried at 60° C. to obtain the mussel mucin inner layer.

5. The low-temperature heat-sealed composite film for pharmaceutical packaging according to claim 4, characterized in that: The method for preparing the modified mussel mucin powder in step A1 comprises the following steps: Step B1, adding mussel mucin to PBS buffer, then adding acrylic acid and potassium persulfate, and simultaneously adding hydrochloric acid dropwise to adjust the pH to 4.8-5.2, and bathing at 58-62° C. in water for 3-4 hours to obtain a primary product; Step B2, adding 0.5-1wt% of genipin to the initial product, standing at room temperature for 10-14 hours, dialyzing to remove unreacted monomers, and freeze-drying to obtain modified mussel mucin powder.

6. The low-temperature heat-sealed composite film for pharmaceutical packaging according to claim 5, characterized in that: In step B1, the mass ratio of mussel mucin, acrylic acid, potassium persulfate and PBS buffer is 1:0.03-0.07:0.004-0.006:10-12; the concentration of the PBS buffer is 0.01-0.02 mol / L; and the concentration of the hydrochloric acid is 0.1-0.2 mol / L.

7. The low-temperature heat-sealed composite film for pharmaceutical packaging according to claim 4, characterized in that: In step A1, the polyester film is subjected to plasma treatment. The specific operation is to introduce argon and oxygen in a ratio of 4:1, set the power to 200-300W, and perform plasma treatment for 86-94s.

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