A breathable and permeable transdermal patch and its preparation method

Abstract

This invention discloses a breathable and permeable transdermal patch and its preparation method, relating to the field of pharmaceutical technology. The method includes the following steps: S1: Adding a drug-loaded MOF and an acrylic-polyethylene glycol copolymer to a gelatin aqueous solution and stirring until homogeneous to obtain a drug-loaded gel solution; S2: Applying the drug-loaded gel solution to a substrate surface and allowing it to stand at room temperature to form a drug-loaded gel layer; attaching a protective film to obtain the transdermal patch. The transdermal patch prepared in this application, through a specific synergistic effect between the drug-loaded MOF and the acrylic-polyethylene glycol copolymer, can not only inhibit the crystallization of berberine hydrochloride but also significantly improve the penetration efficiency of the berberine hydrochloride hydrogel transdermal patch into the stratum corneum of the skin, ensuring stable and long-lasting release of berberine hydrochloride. It exhibits good permeability and breathability, meeting the requirements of hydrogel transdermal patches.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a breathable and permeable transdermal patch and its preparation method. Background Technology

[0002] Transdermal patches are a novel type of formulation that delivers medication locally by loading the medication into a patch and applying it to the skin. The medication then penetrates the stratum corneum and enters the body's circulation. Compared to traditional oral or injectable routes of administration, transdermal patches offer several advantages. They avoid the first-pass effect in the liver, minimizing impact on organs such as the liver and reducing systemic toxicity. Furthermore, transdermal patches are convenient to use and offer significant advantages for chronic diseases requiring long-term medication, such as hypertension, pain management, and localized inflammation.

[0003] With the continuous development of pharmaceutics, transdermal drug delivery systems have become one of the main research directions in drug delivery, and the core technology lies in achieving efficient and sustained drug release.

[0004] Berberine hydrochloride is an isoquinoline alkaloid extracted from traditional Chinese medicinal herbs such as Coptis chinensis and Phellodendron amurense. It possesses antibacterial, anti-inflammatory, and analgesic properties and is primarily used clinically to treat intestinal infections and bacillary dysentery. In recent years, it has been discovered that berberine hydrochloride can be administered not only orally but also topically, leading to increased interest in its applications in skin disease treatment and local inflammation control.

[0005] CN120305373B discloses a traditional Chinese medicine gel patch, which is formed by components such as azide-polyethylene glycol-carboxylic acid and silk fibroin to reduce swelling and promote stable drug release. However, the gel network is a dense, non-porous network and lacks air permeability.

[0006] However, actual research has found that berberine hydrochloride has poor stability in hydrogels and is prone to crystallization. At the same time, its quaternary ammonium salt molecular structure makes it difficult to effectively penetrate the skin's stratum corneum barrier, resulting in low transdermal efficiency and inability to maintain long-term effective release. The precipitated drug crystals block or even destroy the gel network structure, further reducing the permeability of the hydrogel transdermal patch and seriously affecting its use and development.

[0007] In summary, the development of a breathable and permeable transdermal patch and its preparation method are of great significance in addressing the aforementioned issues. Summary of the Invention

[0008] The purpose of this invention is to provide a breathable and permeable transdermal patch and its preparation method, so as to solve the problems mentioned in the background art.

[0009] To solve the above-mentioned technical problems, the present invention provides the following technical solution: A method for preparing a breathable and permeation-enhancing transdermal patch includes the following steps: S1: Add the drug-loaded MOF and acrylic acid-polyethylene glycol copolymer to the gelatin aqueous solution and stir evenly to obtain the drug-loaded gel solution; S2: Apply the drug-loaded gel liquid to the surface of the substrate, let it stand at room temperature to form a drug-loaded gel layer; attach a protective film to obtain a transdermal patch.

[0010] More preferably, the drug-loaded gel liquid comprises the following raw materials: by weight, 2-3 parts drug-loaded MOF, 0.5-0.8 parts acrylic acid-polyethylene glycol copolymer, and 6-7 parts gelatin; The concentration of gelatin in the gelatin aqueous solution is 6-7 wt%.

[0011] Ideally, the drug-loaded MOF is ZIF-90.

[0012] In a more optimized manner, the preparation method of the drug-loaded MOF is as follows: S1-1: ZIF-90 and sodium borohydride are added to methanol and reacted at 55~65℃ for 2~3h, purified and dried to obtain reduced ZIF-90; S1-2: Reduced ZIF-90, 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane, and methoxy polyethylene glycol silane were added to an aqueous ethanol solution and reacted at 50-60°C for 8-10 hours; then berberine hydrochloride was added, stirred evenly, and dried to obtain the drug-loaded MOF.

[0013] Ideally, the molecular weight of the methoxy polyethylene glycol silane is 1000~2000 Da.

[0014] In a more optimized manner, the mass ratio of ZIF-90 to sodium borohydride in the reduced ZIF-90 is 4:(1~1.5); In the drug-loaded MOF, the mass ratio of reduced ZIF-90, 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane, methoxy polyethylene glycol silane, and berberine hydrochloride is 1:(0.03~0.05):(0.015~0.025):(0.08~0.1).

[0015] A more optimized method for preparing the acrylic acid-polyethylene glycol copolymer is as follows: under a nitrogen atmosphere, methacrylic acid, polyethylene glycol methyl ether methacrylate, and azobisisobutyronitrile are added to anhydrous ethanol, reacted at 80-90°C for 4-6 hours, purified and dried to obtain the acrylic acid-polyethylene glycol copolymer.

[0016] Ideally, the molecular weight of the polyethylene glycol methyl ether methacrylate is 3000~5000 Da.

[0017] In a more optimized manner, the mass ratio of methacrylic acid, polyethylene glycol methyl ether methacrylate, and azobisisobutyronitrile in the acrylic acid-polyethylene glycol copolymer is (0.5~0.6):(10~12):(0.32~0.36).

[0018] Compared with the prior art, the beneficial effects achieved by the present invention are: This application uses drug-loaded MOF, acrylic acid-polyethylene glycol copolymer, and gelatin as raw materials to form a stable drug-loaded gel layer through compounding. The drug-loaded MOF inhibits drug crystallization, and the copolymer stabilizes the gel network, synergistically achieving long-lasting permeability and good breathability of the transdermal patch.

[0019] Using ZIF-90 as the basic framework, after reduction with sodium borohydride, sulfonic acid groups and polyethylene glycol chains of a specific molecular weight (1000~2000 Da) are grafted onto it to form a drug-loaded MOF (Medium-Oxygen Fiber) containing berberine hydrochloride. The porous structure of the MOF provides high drug loading, stable mechanical properties, and inhibits crystal formation. The sulfonic acid groups can form specific electrostatic interactions with the cationic structure of berberine hydrochloride, enhancing the stability of berberine hydrochloride within the MOF. The specific molecular weight polyethylene glycol (smaller molecule) avoids excessive grafting that could lead to excessive MOF clogging, improves hydrophilicity, and enhances the dispersibility and stability of the drug-loaded MOF in the hydrogel substrate. Simultaneously, the introduction of specific hydrophilic flexible segments can improve the interfacial interaction with the stratum corneum of the skin, promoting product permeability.

[0020] However, although drug-loaded MOFs can improve the stability and permeability of drugs to some extent, drug-loaded MOFs in hydrogel networks still affect their stability, leading to a decrease in overall mechanical properties. Drug-loaded MOF particles cannot be evenly dispersed or even agglomerate, which in turn affects air permeability and long-term permeability.

[0021] Therefore, this application further introduces an acrylic acid-polyethylene glycol copolymer. By introducing a small amount of polyethylene glycol chains with a specific molecular weight (3000~4000Da), the compatibility with gelatin and drug-loaded MOF is improved, while the hydrogel network is adjusted to prevent drug-loaded MOF aggregation, improve dispersibility, and enhance breathability. Acrylic acid and gel molecules interact through hydrogen bonds, thereby improving the compatibility of each component, enhancing interfacial interaction, and improving the mechanical stability of the gel network. This improves the long-lasting penetration and breathability of the transdermal patch.

[0022] It is important to note that the polyethylene glycol segments in both the drug-loaded MOF and the acrylic-polyethylene glycol copolymer in this application require specific molecular weights. This is because: if the molecular weight of the polyethylene glycol segments in the drug-loaded MOF is too large (5000 Da), it will excessively clog the MOF pores, failing to prevent berberine hydrochloride aggregation and reducing drug loading efficiency; conversely, if the polyethylene glycol segments in the acrylic-polyethylene glycol copolymer are too small, it will be difficult to form a stable hydrophilic network in the hydrogel matrix, thus affecting the long-term permeability of berberine hydrochloride in the transdermal patch and failing to meet the permeability requirements for topical administration. Detailed Implementation

[0023] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0024] It should be noted that the following quantities are by weight. There are no special restrictions on the manufacturers of the raw materials involved in this invention. Exemplary examples include: methoxy polyethylene glycol silane with a molecular weight of 1000; methoxy polyethylene glycol silane with a molecular weight of 5000; polyethylene glycol methyl ether methacrylate with a molecular weight of 4000, catalog number P675693-250mg, purchased from Maclean's; polyethylene glycol methyl ether methacrylate with a molecular weight of 2000, catalog number P675699-250mg, purchased from Maclean's; ZIF-90 with catalog number 6678157, purchased from Maclean's; 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane with CAS number 126519-89-9; berberine hydrochloride with CAS number 633-65-8, purchased from Shaanxi Kehong Health Industry Co., Ltd.; and other raw materials are all commercially available.

[0025] Example 1: A method for preparing a breathable and permeable transdermal patch, comprising the following steps: S1: Add 2 parts of drug-loaded MOF and 0.5 parts of acrylic acid-polyethylene glycol copolymer to a gelatin aqueous solution (6.5 parts gelatin; the concentration of gelatin in the gelatin aqueous solution is 6.5 wt%), stir evenly to obtain a drug-loaded gel solution; S2: Apply the drug-loaded gel liquid to the surface of the substrate, let it stand at room temperature to form a drug-loaded gel layer; attach a protective film to obtain a transdermal patch; The preparation method of drug-loaded MOF is as follows: S1-1: 4 parts ZIF-90 and 1.3 parts sodium borohydride are added to methanol and reacted at 60℃ for 2.5h. After purification and drying, reduced ZIF-90 is obtained. S1-2: 1 part of reduced ZIF-90, 0.04 parts of 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane, and 0.02 parts of methoxy polyethylene glycol silane (1000 Da) were added to a 70 wt% aqueous ethanol solution and reacted at 55 °C for 9 h; then 0.08 parts of berberine hydrochloride were added, stirred evenly, and dried to obtain the drug-loaded MOF; The preparation method of acrylic acid-polyethylene glycol copolymer is as follows: under nitrogen atmosphere, 0.55 parts of methacrylic acid, 11 parts of polyethylene glycol methyl ether methacrylate (4000 Da) and 0.34 parts of azobisisobutyronitrile are added to anhydrous ethanol and reacted at 85°C for 5 h. After purification and drying, acrylic acid-polyethylene glycol copolymer is obtained.

[0026] Example 2: A method for preparing a breathable and permeation-enhancing transdermal patch, comprising the following steps: S1: Add 2.3 parts of drug-loaded MOF and 0.6 parts of acrylic acid-polyethylene glycol copolymer to a gelatin aqueous solution (6.5 parts of gelatin; the concentration of gelatin in the gelatin aqueous solution is 6.5 wt%), stir evenly to obtain a drug-loaded gel solution; S2: Apply the drug-loaded gel liquid to the surface of the substrate, let it stand at room temperature to form a drug-loaded gel layer; attach a protective film to obtain a transdermal patch; The preparation method of drug-loaded MOF is as follows: S1-1: 4 parts ZIF-90 and 1.3 parts sodium borohydride are added to methanol and reacted at 60℃ for 2.5h. After purification and drying, reduced ZIF-90 is obtained. S1-2: 1 part of reduced ZIF-90, 0.04 parts of 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane, and 0.02 parts of methoxy polyethylene glycol silane (1000 Da) were added to a 70 wt% aqueous ethanol solution and reacted at 55 °C for 9 h; then 0.085 parts of berberine hydrochloride were added, stirred evenly, and dried to obtain the drug-loaded MOF; The preparation method of acrylic acid-polyethylene glycol copolymer is as follows: under nitrogen atmosphere, 0.55 parts of methacrylic acid, 11 parts of polyethylene glycol methyl ether methacrylate (4000 Da) and 0.34 parts of azobisisobutyronitrile are added to anhydrous ethanol and reacted at 85°C for 5 h. After purification and drying, acrylic acid-polyethylene glycol copolymer is obtained.

[0027] Example 3: A method for preparing a breathable and permeable transdermal patch, comprising the following steps: S1: Add 2.8 parts of drug-loaded MOF and 0.7 parts of acrylic acid-polyethylene glycol copolymer to a gelatin aqueous solution (6.5 parts of gelatin; the concentration of gelatin in the gelatin aqueous solution is 6.5 wt%), stir evenly, and obtain a drug-loaded gel solution; S2: Apply the drug-loaded gel liquid to the surface of the substrate, let it stand at room temperature to form a drug-loaded gel layer; attach a protective film to obtain a transdermal patch; The preparation method of drug-loaded MOF is as follows: S1-1: 4 parts ZIF-90 and 1.3 parts sodium borohydride are added to methanol and reacted at 60℃ for 2.5h. After purification and drying, reduced ZIF-90 is obtained. S1-2: 1 part of reduced ZIF-90, 0.04 parts of 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane, and 0.02 parts of methoxy polyethylene glycol silane (1000 Da) were added to a 70 wt% aqueous ethanol solution and reacted at 55 °C for 9 h; then 0.092 parts of berberine hydrochloride were added, stirred evenly, and dried to obtain the drug-loaded MOF; The preparation method of acrylic acid-polyethylene glycol copolymer is as follows: under nitrogen atmosphere, 0.55 parts of methacrylic acid, 11 parts of polyethylene glycol methyl ether methacrylate (4000 Da) and 0.34 parts of azobisisobutyronitrile are added to anhydrous ethanol and reacted at 85°C for 5 h. After purification and drying, acrylic acid-polyethylene glycol copolymer is obtained.

[0028] Example 4: A method for preparing a breathable and permeation-enhancing transdermal patch, comprising the following steps: S1: Add 3 parts of drug-loaded MOF and 0.8 parts of acrylic acid-polyethylene glycol copolymer to a gelatin aqueous solution (6.5 parts of gelatin; the concentration of gelatin in the gelatin aqueous solution is 6.5 wt%), stir evenly to obtain a drug-loaded gel solution; S2: Apply the drug-loaded gel liquid to the surface of the substrate, let it stand at room temperature to form a drug-loaded gel layer; attach a protective film to obtain a transdermal patch; The preparation method of drug-loaded MOF is as follows: S1-1: 4 parts ZIF-90 and 1.3 parts sodium borohydride are added to methanol and reacted at 60℃ for 2.5h. After purification and drying, reduced ZIF-90 is obtained. S1-2: 1 part of reduced ZIF-90, 0.04 parts of 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane, and 0.02 parts of methoxy polyethylene glycol silane (1000 Da) were added to a 70 wt% aqueous ethanol solution and reacted at 55 °C for 9 h; then 0.1 parts of berberine hydrochloride were added, stirred evenly, and dried to obtain the drug-loaded MOF; The preparation method of acrylic acid-polyethylene glycol copolymer is as follows: under nitrogen atmosphere, 0.55 parts of methacrylic acid, 11 parts of polyethylene glycol methyl ether methacrylate (4000 Da) and 0.34 parts of azobisisobutyronitrile are added to anhydrous ethanol and reacted at 85°C for 5 h. After purification and drying, acrylic acid-polyethylene glycol copolymer is obtained.

[0029] Comparative Example 1: The drug-loaded MOF was adjusted to use only ZIF-90 and berberine hydrochloride physically blended; the rest was the same as in Example 3; the specific differences are as follows: S1: Add 3 parts of drug-loaded MOF and 0.8 parts of acrylic acid-polyethylene glycol copolymer to a gelatin aqueous solution (6.5 parts of gelatin; the concentration of gelatin in the gelatin aqueous solution is 6.5 wt%), stir evenly to obtain a drug-loaded gel solution; S2: Apply the drug-loaded gel liquid to the surface of the substrate, let it stand at room temperature to form a drug-loaded gel layer; attach a protective film to obtain a transdermal patch; The preparation method of drug-loaded MOF is as follows: 10 parts of ZIF-90 and 0.85 parts of berberine hydrochloride are added to a 70wt% ethanol aqueous solution, stirred evenly, and dried to obtain drug-loaded MOF; The preparation method of acrylic acid-polyethylene glycol copolymer is as follows: under nitrogen atmosphere, 0.55 parts of methacrylic acid, 11 parts of polyethylene glycol methyl ether methacrylate (4000 Da) and 0.34 parts of azobisisobutyronitrile are added to anhydrous ethanol and reacted at 85°C for 5 h. After purification and drying, acrylic acid-polyethylene glycol copolymer is obtained.

[0030] Comparative Example 2: The methoxy polyethylene glycol silane (1000 Da) was changed to methoxy polyethylene glycol silane (5000 Da); the rest was the same as in Example 3; the specific differences are as follows: S1: Add 3 parts of drug-loaded MOF and 0.8 parts of acrylic acid-polyethylene glycol copolymer to a gelatin aqueous solution (6.5 parts of gelatin; the concentration of gelatin in the gelatin aqueous solution is 6.5 wt%), stir evenly to obtain a drug-loaded gel solution; S2: Apply the drug-loaded gel liquid to the surface of the substrate, let it stand at room temperature to form a drug-loaded gel layer; attach a protective film to obtain a transdermal patch; The preparation method of drug-loaded MOF is as follows: S1-1: 4 parts ZIF-90 and 1.3 parts sodium borohydride are added to methanol and reacted at 60℃ for 2.5h. After purification and drying, reduced ZIF-90 is obtained. S1-2: 1 part of reduced ZIF-90, 0.04 parts of 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane, and 0.02 parts of methoxy polyethylene glycol silane (5000 Da) were added to a 70 wt% aqueous ethanol solution and reacted at 55 °C for 9 h; then 0.1 parts of berberine hydrochloride were added, stirred evenly, and dried to obtain the drug-loaded MOF; The preparation method of acrylic acid-polyethylene glycol copolymer is as follows: under nitrogen atmosphere, 0.55 parts of methacrylic acid, 11 parts of polyethylene glycol methyl ether methacrylate (4000 Da) and 0.34 parts of azobisisobutyronitrile are added to anhydrous ethanol and reacted at 85°C for 5 h. After purification and drying, acrylic acid-polyethylene glycol copolymer is obtained.

[0031] Comparative Example 3: The polyethylene glycol methyl ether methacrylate (4000 Da) was changed to polyethylene glycol methyl ether methacrylate (1000 Da); the rest was the same as in Example 3; the specific differences are as follows: S1: Add 3 parts of drug-loaded MOF and 0.8 parts of acrylic acid-polyethylene glycol copolymer to a gelatin aqueous solution (6.5 parts of gelatin; the concentration of gelatin in the gelatin aqueous solution is 6.5 wt%), stir evenly to obtain a drug-loaded gel solution; S2: Apply the drug-loaded gel liquid to the surface of the substrate, let it stand at room temperature to form a drug-loaded gel layer; attach a protective film to obtain a transdermal patch; The preparation method of drug-loaded MOF is as follows: S1-1: 4 parts ZIF-90 and 1.3 parts sodium borohydride are added to methanol and reacted at 60℃ for 2.5h. After purification and drying, reduced ZIF-90 is obtained. S1-2: 1 part of reduced ZIF-90, 0.04 parts of 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane, and 0.02 parts of methoxy polyethylene glycol silane (1000 Da) were added to a 70 wt% aqueous ethanol solution and reacted at 55 °C for 9 h; then 0.1 parts of berberine hydrochloride were added, stirred evenly, and dried to obtain the drug-loaded MOF; The preparation method of acrylic acid-polyethylene glycol copolymer is as follows: under nitrogen atmosphere, 0.55 parts of methacrylic acid, 11 parts of polyethylene glycol methyl ether methacrylate (1000 Da) and 0.34 parts of azobisisobutyronitrile are added to anhydrous ethanol and reacted at 85°C for 5 h. After purification and drying, acrylic acid-polyethylene glycol copolymer is obtained.

[0032] Comparative Example 4: Without acrylic acid-polyethylene glycol copolymer; otherwise the same as Example 3; specific differences are as follows: S1: Add 3 parts of drug-loaded MOF to a gelatin aqueous solution (6.5 parts gelatin; the concentration of gelatin in the gelatin aqueous solution is 6.5 wt%), stir evenly, and obtain a drug-loaded gel solution; S2: Apply the drug-loaded gel liquid to the surface of the substrate, let it stand at room temperature to form a drug-loaded gel layer; attach a protective film to obtain a transdermal patch; The preparation method of drug-loaded MOF is as follows: S1-1: 4 parts ZIF-90 and 1.3 parts sodium borohydride are added to methanol and reacted at 60℃ for 2.5h. After purification and drying, reduced ZIF-90 is obtained. S1-2: 1 part of reduced ZIF-90, 0.04 parts of 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane, and 0.02 parts of methoxy polyethylene glycol silane (1000 Da) were added to a 70 wt% aqueous ethanol solution and reacted at 55 °C for 9 h; then 0.1 parts of berberine hydrochloride were added, stirred evenly, and dried to obtain the drug-loaded MOF.

[0033] Performance Test 1: The transdermal patches prepared in Examples 1-4 and Comparative Examples 1-4 were tested for the transdermal effect of berberine hydrochloride in the transdermal patches using the Franz diffusion cell method. The cumulative permeation amount of berberine hydrochloride after 4h, 12h and 24h was tested respectively. The test results are shown in Table 1. Table 1

[0034] Performance Test 2: The drug-loaded gel layer of the transdermal patch prepared in Examples 1-4 and Comparative Examples 1-4 was covered on the mouth of the moisture-permeable cup, sealed, and tested for 24 hours at a relative humidity of 50% to test its water vapor permeability and determine its air permeability; the test results are shown in Table 2. Table 2

[0035] Conclusion: As shown in Tables 1 and 2 above, the transdermal patch prepared in this application has good air permeability and penetration properties. In Examples 1-4, the drug loading increased from low to high, the cumulative permeation of berberine hydrochloride increased from low to high, while the water vapor permeability decreased from high to low. This is because a higher drug loading allows for a higher total amount of drug available for transdermal penetration, thus increasing the cumulative permeation of berberine hydrochloride and the long-lasting permeability. However, at the same time, the drug and carrier occupy more pores, resulting in a relative reduction in water vapor permeability channels, thus slightly decreasing air permeability.

[0036] As shown in the data from Comparative Example 1, when the drug-loaded MOF is modified to use only ZIF-90 and berberine hydrochloride in physical blending, the lack of small molecule polyethylene glycol segments and sulfonic acid groups results in a lack of specific electrostatic interaction with berberine hydrochloride. The drug relies solely on physical adsorption between the drug and the MOF carrier, leading to a decrease in drug loading and stability. At the same time, the unmodified ZIF-90 surface has insufficient hydrophilicity, resulting in decreased compatibility with the hydrophilic gel matrix. Ultimately, this leads to a significant decrease in the long-term permeability and breathability of the transdermal patch. As can be seen from the data of Comparative Example 2, when the methoxy polyethylene glycol silane (1000 Da) is adjusted to methoxy polyethylene glycol silane (5000 Da), the excessively long polyethylene glycol segments will excessively block the MOF surface, which not only hinders the effective loading and release of berberine hydrochloride, but also reduces the dispersion uniformity of MOF in the hydrogel matrix, leading to local drug aggregation, and ultimately reducing the long-term stability and breathability of the transdermal patch. The data from Comparative Example 3 show that when polyethylene glycol methyl ether methacrylate (4000 Da) is adjusted to polyethylene glycol methyl ether methacrylate (1000 Da), the shorter hydrophilic segments cannot form a stable hydrophilic network in the gel, resulting in decreased stability in the hydrogel matrix, affecting the long-term permeability of the drug, and slightly reducing air permeability. The data from Comparative Example 4 show that without the addition of acrylic acid-polyethylene glycol copolymer, the lack of specific amounts of large-molecule polyethylene glycol segments and acrylic acid segments makes the drug-loaded MOF prone to aggregation, significantly reducing dispersion uniformity and long-term stability. Simultaneously, the lack of hydrogen bond interactions between the acrylic acid segments and the gelatin network decreases the mechanical stability of the gel network and the stability of the drug, resulting in a significant decline in the overall performance of the transdermal patch.

[0037] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a breathable and permeable transdermal patch, characterized in that: Includes the following steps: S1: Add the drug-loaded MOF and acrylic acid-polyethylene glycol copolymer to the gelatin aqueous solution and stir evenly to obtain the drug-loaded gel solution; S2: Apply the drug-loaded gel liquid to the surface of the substrate, let it stand at room temperature to form a drug-loaded gel layer; attach a protective film to obtain a transdermal patch; The drug-loaded gel liquid comprises the following raw materials: by weight, 2-3 parts drug-loaded MOF, 0.5-0.8 parts acrylic acid-polyethylene glycol copolymer, and 6-7 parts gelatin; The concentration of gelatin in the gelatin aqueous solution is 6-7 wt%; The preparation method of the drug-loaded MOF is as follows: S1-1: ZIF-90 and sodium borohydride are added to methanol and reacted at 55~65℃ for 2~3h, purified and dried to obtain reduced ZIF-90; S1-2: Reduced ZIF-90, 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane, and methoxy polyethylene glycol silane were added to an aqueous ethanol solution and reacted at 50-60°C for 8-10 hours; then berberine hydrochloride was added, stirred evenly, and dried to obtain the drug-loaded MOF; The molecular weight of the methoxy polyethylene glycol silane is 1000~2000 Da.

2. The method for preparing a breathable and permeation-enhancing transdermal patch according to claim 1, characterized in that: In the reduced ZIF-90, the mass ratio of ZIF-90 to sodium borohydride is 4:(1~1.5); In the drug-loaded MOF, the mass ratio of reduced ZIF-90, 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane, methoxy polyethylene glycol silane, and berberine hydrochloride is 1:(0.03~0.05):(0.015~0.025):(0.08~0.1).

3. The method for preparing a breathable and permeation-enhancing transdermal patch according to claim 1, characterized in that: The acrylic acid-polyethylene glycol copolymer is prepared by adding methacrylic acid, polyethylene glycol methyl ether methacrylate, and azobisisobutyronitrile to anhydrous ethanol under a nitrogen atmosphere, reacting at 80-90°C for 4-6 hours, purifying and drying to obtain the acrylic acid-polyethylene glycol copolymer.

4. The method for preparing a breathable and permeation-enhancing transdermal patch according to claim 3, characterized in that: The molecular weight of the polyethylene glycol methyl ether methacrylate is 3000~5000 Da.

5. The method for preparing a breathable and permeation-enhancing transdermal patch according to claim 3, characterized in that: In the acrylic acid-polyethylene glycol copolymer, the mass ratio of methacrylic acid, polyethylene glycol methyl ether methacrylate, and azobisisobutyronitrile is (0.5~0.6):(10~12):(0.32~0.36).

6. The transdermal patch prepared by the method for preparing a breathable and permeable transdermal patch according to any one of claims 1 to 5.

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