A compound nano piezoelectric material loaded with maslinic acid external application and a preparation method and application thereof

Abstract

The application relates to the technical field of composite piezoelectric materials, and particularly discloses a composite nano piezoelectric material loaded with maslinic acid, a preparation method and application thereof, which comprises the following steps: adding barium titanate nano powder and maslinic acid into a solvent in sequence, performing ultrasonic treatment, then stirring and treating at 50-70 DEG C for 1.5-3h to obtain a mixture; adding PVDF powder into the mixture, stirring and treating at 50-70 DEG C for 4-6h to obtain a final mixed solution; meanwhile, washing and drying a glass slide to obtain a treated glass slide substrate; coating the mixed solution on the glass slide to form a film, drying to obtain a precursor film; and performing polarization treatment on the film to obtain the composite nano piezoelectric material loaded with maslinic acid. By introducing the barium titanate and the maslinic acid, the application effectively induces the PVDF to form a high-content polar beta crystal phase, thereby significantly improving the piezoelectric performance of the PVDF, and meanwhile, the flexibility of the PVDF film is also enhanced, the wearable patch substrate is suitable, and the application exhibits good drug controlled release potential.

Description

Technical Field

[0001] This invention relates to the field of composite piezoelectric materials technology, and in particular to a composite nanopiezoelectric material external patch loaded with hawthorn acid, its preparation method and application. Background Technology

[0002] For symptoms such as pain, swelling, and fever caused by muscle strain, chronic inflammation, bone and joint diseases, and various soft tissue injuries, topical patches have become an important means of relief due to their advantages such as convenient use, localized drug delivery, and few side effects. However, traditional medicated patches mostly rely on passive diffusion and penetration of drugs. Their transdermal efficiency is limited by the stratum corneum barrier, the outermost layer of human skin, resulting in low drug penetration and low bioavailability (especially for many active ingredients that are poorly water- and lipid-soluble). They generally suffer from slow onset of action and poor therapeutic effects.

[0003] To improve transdermal drug delivery efficiency, researchers have developed various physical permeation enhancement techniques, such as iontophoresis, electroporation, and ultrasound-guided delivery. While these methods effectively increase transdermal rates, they typically rely on external power sources, resulting in bulky, costly, and inconvenient systems that fail to meet the growing demand for wearable, self-powered smart drug delivery systems. Piezoelectric materials can directly convert minute external mechanical stresses (such as body movements, muscle vibrations, or slight pressure) into weak surface charges and pulsed electric fields, making it possible to construct self-powered drug delivery systems. Among them, polyvinylidene fluoride (PVDF), a typical piezoelectric polymer, generates electricity based on the directional alignment and changes of dipoles (such as -CF2- groups) within the material under external force, thereby generating a piezoelectric potential on the material surface. This potential can be used to drive drug release.

[0004] PVDF exists in various crystalline phases (α, β, γ, δ, and ε phases), with its excellent piezoelectric properties primarily derived from the polar β phase exhibiting an all-trans (TTTT) conformation. However, under conventional processing conditions, PVDF more readily forms a thermodynamically stable, nonpolar α phase, which lacks piezoelectricity. Although the α phase can be partially transformed into the β phase through subsequent polarization treatment, the piezoelectric coefficient (d) of pure PVDF remains low. 33 The pC / N ratio (usually below 30) is still relatively low, which limits its practical application effectiveness.

[0005] To further enhance the piezoelectric properties of PVDF, introducing inorganic ceramic nanoparticles with high piezoelectric coefficients (such as lead-free barium titanate (BaTiO3)) is a commonly used and effective strategy. This type of composite strategy aims to combine the high piezoelectricity of the inorganic filler with the good flexibility of the polymer matrix. However, inorganic nanoparticles are prone to agglomeration in the polymer matrix, making uniform dispersion difficult. This agglomeration not only weakens the final piezoelectric properties of the composite material but also impairs its flexibility and mechanical integrity, thus limiting its application potential in flexible wearable devices. Summary of the Invention

[0006] To address the above shortcomings, this invention provides a method for preparing a composite nanopiezoelectric material patch loaded with hawthorn acid. This method effectively combines high-voltage electrical properties with good flexibility, making it suitable for permeable patch substrates and possessing good controlled drug release capabilities. The specific technical solution is as follows:

[0007] A method for preparing a topical patch of composite nanopiezoelectric material loaded with hawthorn acid includes the following steps:

[0008] (1) Add barium titanate nanopowder and hawthorn acid to the solvent in sequence, sonicate for 20-40 min, and then stir at 50-70℃ for 1.5-3 h to obtain a homogeneous mixture;

[0009] (2) Then add PVDF powder to the mixture obtained in step (1), stir at 50~70℃ for 4~6h, and then degas to obtain a homogeneous mixed solution;

[0010] (3) Clean and dry the glass slide to obtain a clean glass slide substrate;

[0011] (4) Coat the mixed solution obtained in step (2) onto the glass slide substrate after the treatment in step (3), and then dry it to obtain the precursor film;

[0012] (5) The precursor film obtained in step (4) is subjected to polarization treatment to finally obtain a ceramic nanopiezoelectric composite film loaded with hawthorn acid, which is the ceramic nanopiezoelectric material external patch loaded with hawthorn acid.

[0013] Preferably, in the above-mentioned method for preparing the composite nanopiezoelectric material patch loaded with hawthorn acid, the mass of hawthorn acid is 15-30% of the total mass of barium titanate nanopowder and hawthorn acid, and the mass of barium titanate nanopowder is 1-5% of the mass of PVDF.

[0014] Preferably, in the above-mentioned method for preparing the composite nanopiezoelectric material patch loaded with hawthorn acid, in step (1), the ultrasonic power is 850~1200W and the ultrasonic frequency is 15~25kHz.

[0015] Preferably, in the above-mentioned method for preparing the composite nanopiezoelectric material patch loaded with hawthorn acid, the mass percentage of PVDF in the mixed solution is 12-17%.

[0016] Preferably, in the above-mentioned method for preparing the composite nanopiezoelectric material patch loaded with hawthorn acid, the solvent is NN-dimethylacetamide (DMAc).

[0017] Preferably, in the above-mentioned method for preparing the composite nanopiezoelectric material patch loaded with hawthorn acid, the cleaning process of the glass slide in step (3) is as follows: ultrasonically cleaned in acetone, isopropanol and deionized water for 10-15 min each, and then dried. To further improve the film-forming effect, a small amount of acetone can be quickly wiped on the cleaned and dried glass slide with degreased cotton to form an activated surface.

[0018] Preferably, in the above-mentioned method for preparing the composite nanopiezoelectric material patch loaded with hawthorn acid, the drying process in step (4) is as follows: first, dry at 45℃~55℃ for 1~1.5h; then raise to 75~85℃ and continue drying for 1.5~2.5h.

[0019] Preferably, in the above-mentioned method for preparing the composite nanopiezoelectric material patch loaded with hawthorn acid, in step (4), the film is sandwiched between a pair of planar electrodes, immersed in silicone oil, heated to 80~90℃, polarized for 20~60min under the condition of applying a voltage of 50~85V / μm between the two electrodes, and then cooled to room temperature while keeping the voltage constant.

[0020] Preferably, in the above-mentioned preparation method of the composite nanopiezoelectric material patch loaded with hawthorn acid, in step (2), degassing is performed by vacuuming at room temperature for 15-20 minutes.

[0021] On the other hand, the present invention also provides a ceramic nanopiezoelectric material external patch, which is prepared by the above-described preparation method.

[0022] On the other hand, the present invention also provides the application of the above-mentioned ceramic nanopiezoelectric material external application in the preparation of drug patches.

[0023] Compared with the prior art, the beneficial effects of the present invention are:

[0024] 1. The present invention provides a method for preparing a composite nanopiezoelectric material patch loaded with hawthorn acid. By introducing barium titanate and hawthorn acid, barium titanate and hawthorn acid are introduced to effectively induce PVDF to form a high content of polar β crystal phase, thereby significantly improving the piezoelectric properties of PVDF. This strategy also enhances the flexibility of the PVDF film. The prepared ceramic nanopiezoelectric material has the characteristics of flexibility and good compatibility, making it suitable for wearable patch substrates and possessing good drug controlled release capability.

[0025] 2. The method for preparing the composite nanopiezoelectric material overlay loaded with hawthorn acid of the present invention simultaneously modifies the surface of barium titanate with hawthorn acid, which improves the dispersibility of barium titanate nanoparticles in the PVDF matrix, prevents agglomeration, and has a surface modification effect on barium titanate nanoparticles; the combination of hawthorn acid and barium titanate nanoparticles has a synergistic effect of inducing β-phase enhancement and strong interfacial coupling in PVDF, significantly improving the piezoelectric coefficient d of the composite film. 33 This allows it to generate stronger piezoelectric signals in the physiological microenvironment; it also has pharmacological activity and improves biological activity, and can reduce inflammation and relieve pain, thus helping to alleviate discomfort. Attached Figure Description

[0026] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0027] Figure 1 Characterization images of the piezoelectric material external application of the present invention: A is a SEM image of the PVDF film prepared in Comparative Example 1; B is a SEM image of barium titanate powder (BTO); C is a SEM image of the ceramic nanopiezoelectric material external application (MA-PF@BTO) prepared in Example 1.

[0028] Figure 2 XRD patterns of ceramic nanopiezoelectric material patch (MA-PF@BTO) in Example 1, PVDF film (PF), barium titanate (BTO), and succinic acid (MA) in Comparative Example 1 are compared.

[0029] Figure 3 Raman spectra of the ceramic nanopiezoelectric material external application in Example 1, the pure PVDF film (PF) in Comparative Example 1, barium titanate (BTO), and succinic acid (MA) are compared.

[0030] Figure 4 This is an EDS-mapping image of the ceramic nanopiezoelectric material applied in Example 1 of the present invention.

[0031] Figure 5 The image shows the X-ray photoelectron spectroscopy (XPS) spectrum of the ceramic nanopiezoelectric material applied in Example 1 of this invention.

[0032] Figure 6 Comparison of the piezoelectric coefficients of the three films prepared in Example 1, Comparative Example 1, Comparative Example 2 and Comparative Example 3;

[0033] Figure 7The ultrasonic drug release curve of the ceramic nanopiezoelectric material prepared in Example 1 is shown.

[0034] Figure 8 A represents the relative cell viability of the ceramic nanopiezoelectric material patch (MA-PF@BTO) of Example 1, the PVDF membrane (PVDF) of Comparative Example 1, and the membrane (PF@BTO) of Comparative Example 2; B represents the cell absorbance (OD450nm) of the ceramic nanopiezoelectric material patch (MA-PF@BTO) of Example 1, the PVDF membrane (PVDF) of Comparative Example 1, and the membrane (PF@BTO) of Comparative Example 2.

[0035] Figure 9 This is an image of a knee joint tissue section stained with hematoxylin and eosin, and stained with Safranin O-Fast Green, as shown in Example 1 of the present invention.

[0036] Figure 10 This is a bar chart of TNF-α levels in Application Example 1 of the present invention;

[0037] Figure 11 This is a bar chart showing the interleukin-6 (IL-6) content in Application Example 1 of the present invention;

[0038] Figure 12 ALP staining and Alizarin Red (ARS) staining images of BMSCs in Application Example 2 of this invention;

[0039] Figure 13 This is a bar chart of ALP staining quantitative analysis in Application Example 2 of the present invention;

[0040] Figure 14 This is a WB analysis band diagram of osteoblast-specific markers (RUNX2, OCN) in Application Example 2 of the present invention;

[0041] Figure 15 This is a comparison of the quantitative bar graphs of the band intensity of RUNX2, an osteoblast-specific index, in WB analysis in Example 2 of this invention.

[0042] Figure 16 This is a comparison of the quantitative bar graphs of the band intensity of OCN, an osteoblast-specific indicator, in application example 2 of this invention. Detailed Implementation

[0043] The specific embodiments of the present invention are described in detail below, but it should be understood that the scope of protection of the present invention is not limited to the specific embodiments. Unless otherwise defined, all technical terms used below have the same meaning as commonly understood by those skilled in the art. The technical terms used herein are for the purpose of describing specific embodiments only and are not intended to limit the scope of protection of the present invention. Unless otherwise specifically stated, all raw materials, reagents, instruments, and equipment used in the present invention are commercially available or can be prepared by existing methods.

[0044] Source of materials:

[0045] Table 1 Source of Raw Materials

[0046]

[0047] Maslinic acid is a natural pentacyclic triterpenoid compound widely found in plants such as olives and hawthorns. Numerous studies have shown that maslinic acid possesses remarkable anti-inflammatory, antioxidant, antibacterial, antitumor, and collagen-synthesizing promoting activities, demonstrating significant effects in treating inflammatory pain and promoting wound healing. However, maslinic acid itself has poor water and lipid solubility, resulting in low transdermal absorption efficiency, which severely limits its application in topical formulations.

[0048] The structure of hawthorn acid is as follows:

[0049]

[0050] Maslinic acid (MA).

[0051] Example 1

[0052] A method for preparing a topical patch of composite nanopiezoelectric material loaded with hawthorn acid includes the following steps:

[0053] (1) Weigh 0.009g of barium titanate nanoparticles and 3mg of hawthorn acid and add them to a small glass bottle. Add a total of 0.9g of N,N-dimethylacetamide (DMAc) solvent (approximately 0.96ml) to the glass bottle. After sealing the glass bottle, place it in an ultrasonic cleaner and sonicate for 30min. The ultrasonic power is 1000W and the ultrasonic frequency is 20kHz. Then place the glass bottle on a magnetic stirrer and stir continuously at 60℃ for 2h at a stirring speed of 500rpm. This allows the hawthorn acid to fully modify the surface of the barium titanate particles, resulting in a modified barium titanate suspension. Modification with hawthorn acid improves the dispersibility of barium titanate nanoparticles in the PVDF matrix and prevents agglomeration, which is the way to obtain a high-performance composite film.

[0054] (2) Pour all the modified barium titanate suspension obtained in step (1) into a clean weighing bottle, add 0.788 g of approximately 0.84 ml of DMAc solvent; place the container on a magnetic stirrer and stir at low speed; slowly and in batches sprinkle 0.300 g of PVDF powder into the solvent to avoid clumping. After all the powder has been added, seal the container and stir continuously at 60°C for 5 hours at a stirring speed of 500 rpm to obtain a homogeneous mixed solution;

[0055] Place the mixed solution along with the container into a vacuum drying oven and evacuate at room temperature (-0.095MPa) for 20 minutes, or until no bubbles are generated on the surface of the solution;

[0056] (3) Clean the glass slides sequentially with acetone, isopropanol and deionized water for 10 minutes to remove any grease, organic contaminants and other impurities that may be attached to the surface of the glass slides, ensuring that the substrate is clean. Then dry them in a clean oven. Since the surface of the glass slides is smooth, the PVDF film can usually be peeled off directly after drying without the need for a release agent. To ensure better film formation, you can quickly wipe the cleaned glass slides with a small amount of acetone using a cotton swab, let them stand for 2 minutes to form an activated surface, which is more conducive to film formation and obtain the treated glass slides.

[0057] (4) Use a pipette to take an appropriate amount of the degassed mixed solution and drop it evenly onto the glass slide treated in step (3) to coat it; place the glass slide with the wet film horizontally in an oven at 50°C and let it stand for 1 hour; this mild evaporation condition is conducive to the exchange of solvent and non-solvent (moisture in the air), inducing liquid-solid phase separation, thereby effectively inducing the formation of β crystals in PVDF molecular chains; raise the oven temperature to 80°C and continue drying for 2 hours to completely remove residual solvent and obtain a film with a thickness of 50 μm;

[0058] The purpose of using a 50°C oven for the first time here is to achieve vapor-induced phase separation (VIPS). In this mild initial drying stage at 50°C, the key driving force is not thermal energy, but chemical potential. DMAc molecules on the solution surface will evaporate into the air. At the same time, a large number of water vapor molecules contained in the air inside the oven are also constantly and slowly diffusing and dissolving into the solution film. Since DMAc and water are infinitely miscible, the water molecules entering the solution will reduce the solubility of PVDF in the local area. This process is like quietly adding a "non-solvent" dropwise to a solution, causing the solution to gradually transition from a homogeneous, stable state to a metastable phase-separated region. This process is dynamic and slow, achieving an "exchange" between the solvent and the non-solvent. This slow, water vapor-induced phase separation process provides ideal conditions for the PVDF molecular chains to transform from a disordered solution state into an ordered crystal structure. It allows the molecular chains sufficient time to stretch and orient themselves, thus preferentially forming the thermodynamically metastable but piezoelectrically superior β-type crystal. If rapid drying is initiated at 80°C or even higher temperatures, the solvent evaporates too quickly, and the molecular chains do not have enough time to rearrange, making it easier to form the common α-type crystal.

[0059] (5) Polarize the membrane obtained in step (4):

[0060] Electrode preparation: Cut the film into a 2cm×2cm square sample, apply conductive silver paste to the center area of ​​the upper and lower surfaces of the film with a fine brush or toothpick, and dry to form a circular electrode with a diameter of about 0.8-1cm.

[0061] Polarization device setup: Pour an appropriate amount of silicone oil into a small beaker (to prevent arc breakdown); hold the thin film sample with tweezers and immerse it in the silicone oil; attach a copper electrode to the top and bottom of the thin film and connect it to the output line of the high-voltage power supply.

[0062] Polarization conditions: Place the beaker in an 80℃ oven and apply a DC electric field of 80V / μm; for a 50μm thick film, the required voltage is 80×50=4000V (4 kV); polarize for 30 minutes at 80℃ and 4 kV; keep the voltage constant, turn off the oven, and allow the sample to cool naturally to room temperature; disconnect the high voltage power supply, remove the sample, and use filter paper to absorb the surface silicone oil to obtain the ceramic nanopiezoelectric material external coating, denoted as MA-PF@BTO.

[0063] Comparative Example 1 (pure PVDF membrane)

[0064] A method for preparing a piezoelectric material external patch includes the following steps:

[0065] (1) Slowly and in batches add 0.300g of PVDF powder to 1.7g of DMAc solvent to avoid clumping; after all the powder has been added, seal the container and stir continuously at 60℃ for 5h at a stirring speed of 500rpm; place the solution and container in a vacuum drying oven and vacuum (-0.095MPa) at room temperature for about 20min, or until no bubbles are generated on the surface of the solution to obtain the solution;

[0066] (3) Clean the glass slides in acetone, isopropanol and deionized water by ultrasonic cleaning for 10 minutes in sequence, and dry them in a clean oven. Since the surface of the glass slides is smooth, the PVDF film can usually be peeled off directly after drying without the need for a release agent. After cleaning, use a small amount of acetone to quickly wipe the glass slides with degreased cotton, let them stand for 2 minutes to form an activated surface, which is more conducive to film formation, and obtain the treated glass slides.

[0067] (4) Use a pipette to take an appropriate amount of the degassed solution and drop it evenly onto the glass slide treated in step (3) to coat the film; place the glass slide with the wet film horizontally in an oven at 50°C and let it stand for 1 hour; raise the oven temperature to 80°C and continue drying for 2 hours to completely remove the residual solvent and obtain a film with a thickness of 50 μm.

[0068] (5) Electrode preparation: Cut the film into a square sample of 2cm×2cm, apply conductive silver paste to the central area of ​​the upper and lower surfaces of the film with a fine brush or toothpick, dry it to form a circular electrode with a diameter of about 0.8-1cm.

[0069] Polarization device setup: Pour an appropriate amount of silicone oil into a small beaker (to prevent arc breakdown); hold the thin film sample with tweezers and immerse it in the silicone oil; attach a copper electrode to the top and bottom of the thin film and connect it to the output line of the high-voltage power supply.

[0070] Polarization conditions: Place the beaker in an 80℃ oven and apply a DC electric field of 80V / μm; for a 50μm thick film, the required voltage is 80×50=4000V (4 kV); polarize for 30 minutes at 80℃ and 4 kV; keep the voltage constant, turn off the oven, and allow the sample to cool naturally to room temperature; disconnect the high voltage power supply, remove the sample, and use filter paper to absorb the surface silicone oil to obtain the piezoelectric material coating, denoted as PVDF.

[0071] Comparative Example 2

[0072] A method for preparing a piezoelectric material external patch includes the following steps:

[0073] (1) Weigh 0.012g of barium titanate nanoparticles and add them together to a small glass bottle containing a total of 0.9g of DMAc solvent (approximately 0.96ml); after sealing the glass bottle, place it in an ultrasonic cleaner and sonicate for 30min at an ultrasonic power of 1000W and an ultrasonic frequency of 20kHz; then place the glass bottle on a magnetic stirrer and stir continuously at 60℃ for 2h at a stirring speed of 500rpm to obtain a barium titanate suspension;

[0074] (2) Pour all the barium titanate suspension obtained in step (1) into a clean weighing bottle, add 0.788 g of approximately 0.84 ml of DMAc solvent; place the container on a magnetic stirrer and stir at low speed; slowly and in batches sprinkle 0.300 g of PVDF powder into the solvent to avoid clumping. After all the powder has been added, seal the container and stir continuously at 60°C for 5 hours at a stirring speed of 500 rpm to obtain a mixed solution;

[0075] Place the solution and container in a vacuum drying oven and evacuate at room temperature (-0.095 MPa) for about 20 minutes, or until no bubbles are generated on the surface of the solution, to obtain a mixed solution;

[0076] (3) Clean the glass slides in acetone, isopropanol and deionized water by ultrasonic cleaning for 10 minutes in sequence, and dry them in a clean oven. Since the surface of the glass slides is smooth, the PVDF film can usually be peeled off directly after drying without the need for a release agent. To ensure that nothing goes wrong, you can use a small amount of acetone to wipe the cleaned glass slides quickly with degreased cotton, let them stand for 2 minutes to form an activated surface, which is more conducive to film formation and to obtain the treated glass slides.

[0077] (4) Use a pipette to take an appropriate amount of the degassed mixed solution and drop it evenly onto the glass slide treated in step (3) to coat the film; place the glass slide with the wet film horizontally in an oven at 50°C and let it stand for 1 hour; raise the oven temperature to 80°C and continue drying for 2 hours to completely remove the residual solvent and obtain a film with a thickness of 50 μm.

[0078] (5) Electrode preparation: Cut the film into a square sample of 2cm×2cm, apply conductive silver paste to the central area of ​​the upper and lower surfaces of the film with a fine brush or toothpick, dry it to form a circular electrode with a diameter of about 0.8-1cm.

[0079] Polarization device setup: Pour an appropriate amount of silicone oil into a small beaker (to prevent arc breakdown); hold the thin film sample with tweezers and immerse it in the silicone oil; attach a copper electrode to the top and bottom of the thin film and connect it to the output line of the high-voltage power supply.

[0080] Polarization conditions: Place the beaker in an 80℃ oven and apply a DC electric field of 80V / μm; for a 50μm thick film, the required voltage is 80×50=4000V (4 kV); polarize for 30 minutes at 80℃ and 4 kV; keep the voltage constant, turn off the oven, and allow the sample to cool naturally to room temperature; disconnect the high voltage power supply, remove the sample, and use filter paper to absorb the surface silicone oil to obtain the piezoelectric material external coating, denoted as PF@BTO.

[0081] Comparative Example 3

[0082] A method for preparing a piezoelectric material external patch includes the following steps:

[0083] (1) Slowly and in batches, add 0.300g of PVDF powder to 1.688g of DMAc solvent and stir slowly to avoid clumping; then add 0.009g of barium titanate nanoparticles and 3mg of hawthorn acid in sequence; after all the powders have been added, seal the container and stir continuously at 60℃ for 5h at a stirring speed of 500rpm; place the solution and container in a vacuum drying oven and vacuum (-0.095MPa) at room temperature for about 20min, or until no bubbles are generated on the surface of the solution to obtain a mixed solution;

[0084] (2) Clean the glass slides in acetone, isopropanol and deionized water by ultrasonic cleaning for 10 minutes in sequence, and dry them in a clean oven. Since the surface of the glass slides is smooth, the PVDF film can usually be peeled off directly after drying without the need for a release agent. After cleaning, use a small amount of acetone to wipe the glass slides with degreased cotton, let them stand for 2 minutes to form an activated surface, and obtain the treated glass slides.

[0085] (3) Use a pipette to take an appropriate amount of the degassed mixed solution and drop it evenly onto the glass slide treated in step (3) to coat the film; place the glass slide with the wet film horizontally in an oven at 50°C and let it stand for 1 hour; raise the oven temperature to 80°C and continue drying for 2 hours to completely remove the residual solvent and obtain a film with a thickness of 50 μm.

[0086] (4) Polarize the membrane obtained in step (3):

[0087] Electrode preparation: Cut the film into a 2cm×2cm square sample, apply conductive silver paste to the center area of ​​the upper and lower surfaces of the film with a fine brush or toothpick, and dry to form a circular electrode with a diameter of about 0.8-1cm.

[0088] Polarization device setup: Pour an appropriate amount of silicone oil into a small beaker (to prevent arc breakdown); hold the thin film sample with tweezers and immerse it in the silicone oil; attach a copper electrode to the top and bottom of the thin film and connect it to the output line of the high-voltage power supply.

[0089] Polarization conditions: Place the beaker in an 80℃ oven and apply a DC electric field of 80V / μm; for a 50μm thick film, the required voltage is 80×50=4000V (4 kV); polarize for 30 minutes at 80℃ and 4 kV; keep the voltage constant, turn off the oven, and allow the sample to cool naturally to room temperature; disconnect the high voltage power supply, remove the sample, and use filter paper to absorb the surface silicone oil to obtain the piezoelectric material external coating.

[0090] (a) Characterization of piezoelectric materials by XRD, SEM, etc.:

[0091] Figure 1 The images shown are SEM characterization images of the piezoelectric materials prepared in Example 1, Comparative Example 1, and Comparative Example 2. Figure 1 The AC image presents scanning electron microscope (SEM) images of PVDF (prepared in Comparative Example 1), BTO, and MA-PF@BTO (prepared in Example 1). Microscopic observation shows that BTO is uniformly distributed. The characteristic elemental distribution features of BTO (TiBaO3) and MA are clearly distinguishable and highly consistent with the microscopic morphological observation results. This preliminarily proves the successful synthesis of MA-PF@BTO piezoelectric films.

[0092] Figure 2 The XRD patterns of the corresponding samples show that pure BTO exhibits typical perovskite crystal structure peaks. After the formation of the MA-PF@BTO composite, diffraction peaks of both BTO and PVDF appear in the spectrum. Notably, in the final MA-PF@BTO composite, the characteristic peak positions of PVDF change significantly. In particular, the intensity of the diffraction peak at ~20.6° is significantly enhanced, corresponding to the (110) / (200) crystal plane of PVDF, which is a characteristic peak of the β phase. This result indicates that the introduction of BTO induces a transformation of the PVDF matrix from a nonpolar α phase to a highly polar β phase. The increase in β phase content is a key factor in enhancing the piezoelectric properties of the material.

[0093] Raman spectroscopy ( Figure 3 The results showed that, compared with simple PVDF, the stretching vibration peak of the C=O double bond usually appears at ~840 cm⁻¹. -1 Nearby (marked by the blue line in the image), in the spectrum of MA-PF@BTO (pink curve), this was originally at 840 cm⁻¹ -1 The nearby peaks have clearly shifted towards lower wavenumbers (redshift), reaching approximately 830 cm⁻¹. -1 Location (as shown by the pink line).

[0094] Scientific Significance: This "redshift" phenomenon is the gold standard for judging intermolecular interactions in Raman spectroscopy. It indicates that the chemical bond of the C=O group on the PVDF chain is weakened. This is usually because the oxygen atom on the C=O group forms an intermolecular hydrogen bond with the hydroxyl group (-OH) on the sorbic acid (MA) molecule. The formation of the hydrogen bond pulls the electron cloud of the C=O double bond, causing its vibrational frequency to decrease, which is thus manifested in the spectrum as a peak shift to a lower wavenumber.

[0095] The above results confirm that the successfully prepared material is not a simple physical mixture, but a composite material with strong interactions. Hydrogen bonds exist between PVDF and MA, which is one of the key driving forces inducing the transformation of PVDF from the α phase to the piezoelectric β phase. In the MA-PF@BTO composite, MA acts as a "molecular bridge": one end of MA is modified on the surface of BTO particles, while the other end is bonded to the PVDF matrix via hydrogen bonds, thereby improving the dispersion of BTO nanoparticles in the PVDF matrix and enhancing interfacial bonding. Synergistic effect: The introduction of BTO provides heterogeneous nucleation sites, while the interfacial modification of MA further optimizes interfacial interactions. Together, they more effectively induce the formation of PVDF β crystals. This formation of β crystals, and the resulting "β-wave enhancement" phenomenon, directly leads to the strengthening of the material's macroscopic polarization effect. This enhanced polarization capability is crucial for biological applications such as regulating cell behavior through piezoelectric signals, laying a solid materials science foundation for subsequent biological experimental performance.

[0096] Figure 4 The figure shows the EDS-mapping diagram of the MA-PF@BTO piezoelectric material prepared in Example 1. As can be seen from the figure, the mapping diagrams of all elements (C, O, F, Ti, Ba) exhibit highly consistent and uniform distribution signals, covering the entire observation area. This indicates that the barium titanate nanoparticles have achieved uniform nanoscale dispersion in the PVDF matrix, without significant macroscopic agglomeration. This uniform dispersion is crucial for avoiding stress concentration and ensuring uniform material properties. Although the C and O signals in MA overlap with those in PVDF and BTO, the uniform distribution of O suggests that MA molecules have been successfully integrated into the composite material system and have good compatibility with the matrix, without phase separation. The elemental analysis results further confirm the successful loading of PVDF and MA.

[0097] Figure 5X-ray photoelectron spectroscopy (XPS) of the MA-PF@BTO piezoelectric material prepared in Example 1 confirmed the presence of C, O, F, Ba, and Ti elements in the material, corresponding to the characteristic compositions of PVDF, BTO, and sorbic acid (MA). The high-resolution C 1s spectrum can be decomposed into two main components: a CC / C=C bond (graphitized carbon skeleton) at 284.8 eV, and an OC=O bond at 288.4 eV (a characteristic functional group of MA, originating from MA molecules and possible interfacial interactions). The strong peak at 688.5 eV in the F 1s spectrum is attributed to the -CF2- group in PVDF, while the Ba 3d and Ti 2p spectra clearly show the characteristic peak positions of BTO, confirming the successful retention of BaTiO3. These results collectively confirm the successful composite of MA, PF (polyvinylidene fluoride), and BTO, forming a MA-PF@BTO ternary system. The most crucial evidence comes from the detailed analysis of the PVDF phase state in the C 1s spectrum. In the C 1s spectrum of MA-PF@BTO, signal intensities were observed at 284.8 eV (C=C) and 288.4 eV (OC=O). This is not a simple superposition of MA signals; the underlying mechanism lies in the strong intermolecular interactions (such as hydrogen bonds) between the polar functional groups (-COOH, -OH) in the MA molecule and the PVDF chain segments. This interaction effectively guides the alignment of the PVDF molecular chains, prompting a transition from a random helical conformation (nonpolar α phase) to a fully trans conformation (highly polar β phase). XPS's sensitivity to the outermost layer allows it to capture this MA-induced interfacial polarization and phase transition behavior. This significant increase in β phase content, the so-called "β-wave enhancement" effect, is the direct structural source of the enhanced piezoelectricity. The O 1s spectrum further supports the aforementioned interfacial interactions. The peaks at 529.0 eV and 531.5 eV in the spectrum can be attributed to the O ions in the BTO lattice, respectively. 2- And C=O and CO in MA and PVDF. Notably, the O 1s spectrum of MA-PF@BTO shows a certain degree of broadening and binding energy shift, which strongly suggests the formation of a new chemical environment at the three-phase interface of MA, PF, and BTO, and the existence of strong interfacial coupling between MA…FC(PVDF) and MA…O-BTO. This coupling not only stabilizes the structure of the composite material, but more importantly, it establishes an efficient charge transfer pathway. Under external stress, the piezoelectric polarization field generated by BTO can more effectively drive the directional rearrangement of the PVDF β-phase dipoles through this pathway, thereby amplifying the overall piezoelectric output.

[0098] The successful synthesis of MA-PF@BTO and its unique electronic structure have led to the following key roles and effects:

[0099] Piezoelectric properties: The synergistic effect of MA-induced β-wave enhancement and strong interfacial coupling significantly improves the piezoelectric constant d of the composite film. 33 This allows it to generate stronger piezoelectric signals in the physiological microenvironment.

[0100] Promoting osteogenic differentiation: This piezoelectric signal can mimic the natural electrical microenvironment of bone and act directly on mesenchymal stem cells (BMSCs) as a physical stimulation signal, upregulating the expression of osteogenic-related genes (such as Runx2, OCN), accelerating calcium nodule deposition, and thus efficiently guiding bone regeneration (see Application Example 1).

[0101] Improved bioactivity: The bioactivity of MA itself, together with the enhanced polarity of the material surface, promotes the expression of proteins (RUNX2 and OPN) and the adhesion and spread of osteoblasts, creating favorable conditions for bone integration (see Application Example 2).

[0102] (ii) Testing the piezoelectric coefficient of piezoelectric materials

[0103] The piezoelectric coefficient d of the piezoelectric materials prepared in Example 1, Comparative Example 1, Comparative Example 2, and Comparative Example 3 was measured. 33 The determination of [specific value], specifically the test method is as follows:

[0104] The quasi-static method is used for testing. Its core principle is that a low-frequency alternating dynamic force F is applied to the sample, causing the material to generate a charge Q due to the positive piezoelectric effect. The piezoelectric constant d... 33 Defined as the ratio of the electric displacement generated in the direction of stress to the applied stress, in direct measurement, it can be simplified to the ratio of the amount of charge generated to the applied force, i.e., d. 33 =Q / F. The instrument measures F and Q using high-precision sensors, directly calculates and displays d. 33 value.

[0105] Core equipment: High-precision piezoelectric diode 33 Tester: PEAI1000.

[0106] Select measurement function (d) 33 / d 31 / d 15 ), select d 33 Measurement; Select static clamping force 10N; select dynamic force magnitude, select 110Hz / 0.25N; place the sample, click motor control to allow the upper motor to clamp the sample. Wait for the instrument to automatically adjust to ensure that a static force of 10-60N and a dynamic force of 110Hz / 0.25N are applied to the sample; wait for the measurement to complete, the result is generally the true measurement value of the sample after 60 seconds;

[0107] piezoelectric coefficient d 33 See results Figure 6As shown in the figure, the piezoelectric coefficient of Example 1 is significantly higher than that of pure PVDF in Comparative Example 1, indicating that the piezoelectric coefficient (the ability to convert mechanical energy into electrical energy) of the barium titanate (BTO) and ursolic acid (MA) materials is enhanced. Compared with Comparative Example 3, the piezoelectric coefficient of Example 1 is improved, indicating that the modification of barium titanate with ursolic acid can improve the dispersibility of barium titanate nanoparticles in the PVDF matrix, prevent agglomeration, and have a surface modification effect on barium titanate nanoparticles. This enhances the synergistic effect of ursolic acid and barium titanate nanoparticles in inducing β-wave enhancement and strong interfacial coupling in PVDF, significantly improving the piezoelectric coefficient of the composite film. The piezoelectric coefficient of Comparative Example 2 is higher than that of Example 1 because of the higher amount of barium titanate added in Comparative Example 2. However, as can be seen from the figure, the data deviation is large when barium titanate is added directly, indicating poor dispersibility of barium titanate. In summary, the present invention can improve the piezoelectric coefficient of externally applied nanopiezoelectric materials, enabling them to respond to external mechanical stimuli (such as ultrasound) and exert biological functions.

[0108] (III) Ultrasonic drug dynamic release test of piezoelectric materials

[0109] Ultrasonic drug dynamics release testing method for piezoelectric materials: The drug release curve is measured using the dialysis method. The testing principle is based on separating the drug and carrier using a semi-permeable membrane; small molecule drugs can pass through the dialysis membrane into the release medium. The specific steps are as follows:

[0110] (1) Drug loading: In the material preparation step, the model drug MA is dissolved together with PVDF powder in DMAc solvent to uniformly load the drug into the PF@BTO membrane, as shown in the membrane prepared in Example 1.

[0111] (2) Release medium: PBS buffer (pH 7.4) was selected as the release medium to simulate the human body fluid environment. To ensure that the "leakage condition" (i.e., the volume of the release medium is large enough so that the drug concentration is always far below its saturation solubility) is met, the medium volume is usually 50 mL. 0.1% w / v Tween 80 was added to the medium to increase drug solubility.

[0112] (3) Dialysis apparatus: Place the drug-loaded membrane in the dialysis bag. The molecular weight cutoff of the bag should be much larger than the molecular weight of the drug but much smaller than the molecular weight of the material carrier (10 kDa). Immerse the dialysis bag in the release medium.

[0113] (4) Treatment group setup: Experimental group: received ultrasound stimulation (US), control group (non-US group): placed at rest throughout or only oscillated at constant temperature to examine the basal diffusion release of the drug.

[0114] (5) Initial baseline release: The entire dialysis apparatus was placed in a constant temperature shaking incubator (37°C, 100 rpm) and run for 1-2 hours without turning on the sonication. Samples were taken to determine the baseline release concentration of the drug.

[0115] Ultrasound stimulation intervention: Equipment: Ultrasound probe.

[0116] Key parameters:

[0117] Frequency: 1.0 MHz.

[0118] Power / Intensity: Initially set to 0.5-2.0 W / cm², but optimization is required to avoid overheating and damaging cells or materials.

[0119] Mode and time: Pulse mode is used (e.g., 2 seconds of operation followed by 5 seconds of rest), with a total stimulation time of 5 minutes to prevent the medium from overheating. Multiple ultrasonic stimulation time points can be set throughout the entire release cycle (1 hour apart).

[0120] Sampling and replenishment: Take samples before, immediately after, and at longer intervals after ultrasonic stimulation, each time taking 0.5-1 mL of sample and immediately replenish with an isothermal and equal volume of fresh release medium.

[0121] Figure 7 The ultrasonic drug release curve of the piezoelectric material in Example 1 shows that the drug release rate increases significantly under ultrasonic action. The piezoelectric material prepared by this invention can be used as a "smart drug carrier", and its drug release behavior can be remotely and precisely controlled by non-invasive ultrasound.

[0122] (iv) Effects of piezoelectric materials on cell activity

[0123] Assay method for cell viability (CCK-8 assay):

[0124] BMSCs were assessed for viability and virulence by seeding them into 96-well plates (6000-8000 cells per well) with different extracts (each extracted by soaking in complete culture medium for two days) and culturing for 24-120 hours. After treatment, CCK-8 reagent was added to each well and the cells were incubated for 60 minutes. Cell viability was assessed by measuring the absorbance at 450 nm using a microplate reader.

[0125] The results are as follows Figure 8 As shown in AB, Figure 8 A represents the relative viability of cells after 120 hours of culture (the percentage of absorbance of each group relative to the absorbance of the blank control group). Figure 8B represents the absorbance of cells after 24, 72, and 120 hours of culture. The results showed that MA-PF@BTO did not affect cell viability. Moreover, compared with pure PVDF (Comparative Example 1) and PF@BTO (Comparative Example 2), MA-PF@BTO (Example 1) could improve cell viability, indicating that MA-PF@BTO has good biocompatibility.

[0126] Application Example 1: External Application Effect Test

[0127] Osteoarthritis model was established in 6-8 week old SD rats by sodium iodoacetate (MIA) injection (prepared with sterile physiological saline at a concentration of 2 mg / 50 μL).

[0128] Experimental groups: Sham group (sham surgery group), OA group (osteoarthritis model group), OA+MA group, and OA+MA-PF@BTO group.

[0129] The specific steps of the test method include:

[0130] (1) Preoperative preparation

[0131] Rats were acclimatized for one week to confirm the absence of joint disease and infection. MIA working solution was prepared fresh for immediate use, with the required volume calculated based on rat weight and injection dosage (typically 50 μL for a single knee joint injection).

[0132] (2) Intra-articular injection

[0133] Anesthetize rats: Intraperitoneal injection of 1% sodium pentobarbital, and fix the rats in a prone position with the knee joints of the hind limbs exposed after the rats lose consciousness and pain reflexes disappear.

[0134] Local disinfection: Remove hair from the knee joint area, and disinfect the skin with iodine solution and 75% alcohol in turn, covering an area with a diameter of 3-5cm.

[0135] Injection positioning: Fix the knee joint with your left hand and flex it slightly (about 90°). Touch the depression between the lower edge of the patella and the tibial plateau (lateral or medial side of the patellar tendon). Insert the 30 G needle vertically into the joint cavity (the needle depth is about 3-5 mm, and you will feel a sense of emptiness when you have reached the joint cavity).

[0136] Injection procedure: Slowly inject 50 μL of MIA working solution (containing 2 mg MIA), hold for 5 seconds after injection before withdrawing the needle to avoid backflow of the drug solution; the control group (Sham group) was injected with an equal volume of sterile saline.

[0137] Postoperative care: After the rats recover, put them back in their cages and allow them free access to food and water. Keep them in individual cages to avoid fighting. Observe them for 1-2 days to confirm that there is no joint infection (such as redness, swelling, or suppuration).

[0138] Sham group and OA group: No special treatment is performed after modeling;

[0139] OA+MA group: MA (15 mg / kg) was administered by gavage after modeling, once every other day for 4 weeks;

[0140] OA+MA-PF@BTO group: After modeling, an external dressing was applied to the knee joint (Example 1), and the dressing was changed every other day for 4 weeks;

[0141] Experimental results: Rats were sacrificed 4 weeks post-surgery, and knee joint specimens were collected, decalcified, paraffin-embedded, sectioned, and stained with hematoxylin and eosin O-. Results are shown below. Figure 9 ,like Figure 9 As shown:

[0142] Sham group (sham surgery group): The cartilage surface was smooth, the cartilage layer was thick, and the Safranin O staining showed a uniform and dense red color.

[0143] OA group (osteoarthritis model group):

[0144] Results: The cartilage surface was severely worn and incomplete, the cartilage layer was thinned, and the Safranin O staining was very faint or even absent. This indicates that the osteoarthritis model was successfully established, but the cartilage showed severe degenerative changes and a large amount of proteoglycans were lost.

[0145] OA + MA group:

[0146] Results: Cartilage damage was reduced compared to the OA group, and some red staining was visible with Safranin O, but the cartilage surface remained uneven, and the thickness recovery was not ideal. MA had some therapeutic effect, but the effect was limited.

[0147] OA + MA-PF@BTO Team:

[0148] Results: The cartilage surface was much smoother than that of the OA group, and the cartilage thickness was significantly restored. Safranin O staining showed a deep red color similar to that of the Sham group. MA-PF@BTO treatment achieved the best results, effectively promoting the synthesis and deposition of cartilage matrix (proteoglycans) and repairing cartilage structure.

[0149] Figure 10 and Figure 11 (ELISA test)

[0150] Figure 10 The results showed that TNF-α levels in the OA group were significantly higher than those in the Sham group. After treatment with MA-PF@BTO, TNF-α levels decreased significantly, approaching normal levels, demonstrating better efficacy than the OA + MA group.

[0151] Figure 11The results for interleukin-6 (IL-6) levels were completely consistent with the trend of TNF-α. IL-6 levels were extremely high in the OA group, while MA-PF@BTO treatment significantly reduced them.

[0152] The above results indicate that MA-PF@BTO can also effectively inhibit the production of TNF-α and IL-6, and reduce the inflammatory response.

[0153] Structurally, MA-PF@BTO effectively repairs damaged articular cartilage, bringing its morphology and composition closer to normal cartilage. At the inflammatory level, MA-PF@BTO significantly reduces the levels of two key pro-inflammatory factors in osteoarthritis joints, effectively controlling the intra-articular inflammatory environment.

[0154] Application Example 2: Improving Bioactivity Tests

[0155] BMSCs (bone marrow mesenchymal stem cells) were aseptically extracted from the tibia and femur of 4- to 5-week-old C57BL / 6 mice. The bone marrow cavity was flushed with α-MEM medium, and the resulting cell suspension was filtered through a 70-micron cell filter, centrifuged at 1000 rpm, resuspended, and seeded into intact α-MEM medium containing 15% fetal bovine serum (FBS) and 1% penicillin-streptomycin. The cells were then cultured in a humidified incubator at 37°C and 5% CO2.

[0156] Osteogenic induction medium (OIM): prepared from DMEM complete medium supplemented with 10 nmol / L dexamethasone, 50 μg / mL vitamin C, and 5 mmol / L sodium β-glycerophosphate, used to induce osteogenic differentiation. Alkaline phosphoric acid (ALP) activity was measured 7 days after induction; mineralized nodule formation was observed 14 days after induction using Alizarin Red S (ARS) staining.

[0157] The experimental groups are as follows:

[0158] Control group: cultured using OIM only.

[0159] PF@BTO group: cultured using an extract of PF@BTO material (Comparative Example 2) prepared by soaking PF@BTO material in OIM for two days.

[0160] MA-PF@BTO group: cultured using an extract of MA-PF@BTO material (Example 1) prepared by soaking MA-PF@BTO material in OIM for two days.

[0161] Western Blot (WB): Cells were lysed using RIPA lysis buffer containing a 1% protease / phosphatase inhibitor mixture and 1% PMSF. The lysis buffer was centrifuged at 12,000 rpm for 15 minutes at 4°C, and the supernatant was collected as total protein. Proteins were separated by 10% SDS-polyacrylamide gel electrophoresis (SDS-PAGE) at an initial voltage of 80 V, adjusted to 120 V after the sample entered the separating gel, and held for approximately 50 minutes. Subsequently, the protein was transferred to a PVDF membrane (as a carrier) using a wet transfer method. The membrane was blocked with 5% skim milk at room temperature for 120 minutes, then incubated overnight at 4°C with primary antibodies against RUNX-2 (Runt-associated transcription factor 2), osteocalcin (OCN), and β-Actin. After washing with TBST, the membrane was incubated with infrared-labeled goat anti-rabbit IgG (H+L) secondary antibody at room temperature for 50 minutes. Protein bands were detected using an Odyssey infrared imaging system (LI-CORBiosciences), and band intensity was quantitatively analyzed using ImageJ software (v1.8.0, NIH).

[0162] Experimental results: The experimental results are shown in [link to experiment]. Figures 12-16 , Figure 12 Alkaline phosphatase (ALP) staining and Alizarin Red (ARS) staining of BMSCs. Figure 13 For ALP staining and quantitative analysis, Figures 14-16 Western blot analysis of osteoblast-specific markers (RUNX2, OCN). The figure shows that the proliferation and differentiation of MA-PF@BTOergic osteoblasts (BMSCs) create favorable conditions for bone integration.

[0163] In summary, the MA-PF@BTO composite material of this invention successfully combines enhanced piezoelectric properties, ultrasonically responsive controlled drug release, excellent biosafety, and positive cell proliferation-promoting activity, making it a promising advanced biomaterial for smart tissue engineering and controlled drug release.

[0164] The foregoing description of specific exemplary embodiments of the invention is for illustrative and explanatory purposes. These descriptions are not intended to limit the invention to the precise forms disclosed, and it will be apparent that many changes and variations can be made in accordance with the foregoing teachings. The exemplary embodiments were chosen and described in order to explain the specific principles of the invention and its practical application, thereby enabling those skilled in the art to implement and utilize various different exemplary embodiments of the invention, as well as various different choices and variations. The scope of the invention is intended to be defined by the claims and their equivalents.

Claims

1. A method for preparing a topical patch of composite nanopiezoelectric material loaded with hawthorn acid, characterized in that, Includes the following steps: (1) Add barium titanate nanopowder and hawthorn acid to N,N-dimethylacetamide in sequence. The mass of hawthorn acid is 15-30% of the total mass of barium titanate nanopowder and hawthorn acid. Sonicate for 20-40 min, and then stir at 50-70℃ for 1.5-3 h to fully modify the surface of barium titanate particles with hawthorn acid to obtain modified barium titanate suspension. (2) Then, PVDF powder is added to the modified barium titanate suspension obtained in step (1), and the mixture is stirred at 50~70℃ for 4~6h, and then degassed to obtain a mixed solution; the mass percentage of PVDF in the mixed solution is 12~17%, and the mass of barium titanate nanopowder is 1~5% of the mass of PVDF; (3) Clean and dry the glass slide to obtain a pre-treated glass slide substrate; (4) Coat the mixed solution obtained in step (2) onto the glass slide substrate treated in step (3), and then dry it. The drying process is as follows: first dry at 45℃~55℃ for 1~1.5h; then raise to 75~85℃ and continue drying for 1.5~2.5h; to obtain the precursor film; (5) The precursor film obtained in step (4) is polarized to obtain a nano-piezoelectric composite film, which is a ceramic nano-piezoelectric material external patch loaded with hawthorn acid.

2. The method for preparing the composite nanopiezoelectric material patch loaded with hawthorn acid according to claim 1, characterized in that, In step (1), the ultrasonic power is 850~1200W and the ultrasonic frequency is 15~25kHz.

3. The method for preparing the composite nanopiezoelectric material patch loaded with hawthorn acid according to claim 1, characterized in that, In step (3), the glass slide is ultrasonically cleaned in acetone, isopropanol and deionized water for 10-15 minutes in sequence, and then dried.

4. The method for preparing the composite nanopiezoelectric material patch loaded with hawthorn acid according to claim 1, characterized in that, In step (4), the membrane is sandwiched between a pair of planar electrodes, immersed in silicone oil, heated to 80~90℃, polarized for 20~60min under a voltage of 50~85V / μm applied between the two electrodes, and then cooled to room temperature while keeping the voltage constant.

5. A ceramic nanopiezoelectric material external patch, characterized in that, The external dressing is prepared by the preparation method according to any one of claims 1 to 4.

6. The application of the ceramic nanopiezoelectric material as described in claim 5 in the preparation of drug patches.

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