Elutable medicine electronic balloon as well as preparation method and application thereof

Abstract

The invention discloses an elutable medicine electronic balloon as well as a preparation method and application thereof, and belongs to the technical field of medical instruments. The medicine electronic balloon provided by the invention comprises a balloon body and a functional film attached to the balloon body, the functional film comprises a flexible electronic film and a medicine functional layer which are stacked from the balloon body; the flexible electronic film comprises a flexible substrate and a conductive circuit embedded in the flexible substrate; the conductive circuit is in contact with the medicine function layer; the medicine functional layer comprises a biodegradable spinning layer and paclitaxel loaded in the biodegradable spinning layer. The medicine electronic balloon provided by the invention can effectively improve the absorption efficiency of cells at a restenosis position in a stent to paclitaxel medicine, and the balloon body can be repeatedly utilized. The invention further provides a preparation method and application of the medicine electronic balloon.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and in particular to a washable electronic drug balloon, its preparation method, and its application. Background Technology

[0002] Coronary atherosclerosis, or coronary heart disease for short, is the number one disease threatening people's health and safety worldwide, especially in developed and developing countries, where its prevalence is gradually increasing. Therefore, the development of new treatment tools is urgently needed.

[0003] Patients with atherosclerosis often require the placement of vascular stents at the site of vascular stenosis to restore normal blood flow and prevent problems such as myocardial ischemia, hypoxia, and necrosis. However, in-stent restenosis (ISR) can occur within several years after stent placement. Statistics show that the incidence of ISR can reach 20%–30% in bare-metal stents (BMS), while it is lower in drug-eluting stents (DES), but still carries a risk of 5%–10%. Restenosis mainly occurs due to excessive intimal proliferation, smooth muscle cell proliferation, and inflammatory response following vascular wall damage, leading to gradual narrowing of the stent lumen and potentially causing serious consequences such as angina, myocardial infarction, or even heart failure.

[0004] Traditional solutions involve restoring blood flow by mechanically dilating the narrowed area. However, this often leads to excessive proliferation of the vascular intima post-procedure, resulting in a high restenosis rate. The restenosis rate within 6 months after simple balloon angioplasty can reach 30%–50%, severely impacting treatment efficacy and long-term patient prognosis. Due to its poor treatment outcome and prognosis, this method is no longer recommended in clinical practice. Other treatment options include intravascular brachytherapy (IVBT), which involves locally delivering radioactive strontium-90 or yttrium-90 to inhibit fibroblast proliferation. However, this method also damages normal cells, leading to indiscriminate damage and a high rate of late-stage thrombosis. Another option is intravascular lithotripsy (IVL), which uses acoustic shock waves emitted through a balloon system to selectively induce the breakage of calcium deposits in the vessel wall, altering vascular compliance and improving vascular lumen gain and stent expansion. However, IVL also has many problems and limitations. High-energy shock waves can damage the drug polymer coating in drug-eluting stents (DES) or the stent frame itself, thereby impairing the stent's support and the mid-term drug release therapy effect, thus worsening the condition.

[0005] Currently, drug-eluting balloons are the most recommended approach. This involves inserting an interventional balloon, expanding it at the site of stenosis, and placing it close to the blood vessel to uniformly deliver medication—such as paclitaxel—to inhibit smooth muscle cell proliferation. Current balloons need to be held at the affected site for 30–60 seconds. While the released medication provides some therapeutic effect, it is not long-lasting: the recurrence rate within 6 months to 1 year is approximately 5%–10%. Furthermore, the passive diffusion of this drug significantly limits the efficiency of drug uptake by the vessel wall; increasing the balloon's placement time increases the risk of myocardial ischemia. Therefore, increasing the amount of paclitaxel entering the cells within a short timeframe is beneficial for a longer-term and more effective inhibition of proliferation, thereby addressing the problem of in-stent restenosis.

[0006] In summary, traditional methods are not very effective in treating in-stent restenosis. Considering the shortcomings of drug-eluting balloons, there is an urgent need for a method that can deliver drugs quickly and in large quantities, allowing the vascular endothelium to take up enough drugs in a short time, thereby inhibiting intimal hyperplasia and achieving a lower recurrence rate and better treatment results. Summary of the Invention

[0007] This invention aims to address at least one of the technical problems existing in the prior art. To this end, this invention proposes an elutable drug-eluting electronic balloon that can effectively improve the absorption efficiency of drugs such as paclitaxel by cells at the restenosis site within the stent, and the balloon itself is reusable.

[0008] The present invention also provides a method for preparing the above-mentioned drug electronic balloon.

[0009] The present invention also provides the application of the above-mentioned electronic drug balloon.

[0010] According to an embodiment of a first aspect of the present invention, a washable electronic drug balloon is provided, the electronic drug balloon comprising a balloon body and a functional film attached to the balloon body;

[0011] The functional film includes a flexible electronic film and a drug functional layer superimposed from the balloon body;

[0012] The flexible electronic thin film includes a flexible substrate and conductive lines embedded in the flexible substrate; the conductive lines are in contact with the drug functional layer.

[0013] The drug functional layer includes a biodegradable spun layer and a drug loaded therein.

[0014] The electronic drug-eluting balloon according to embodiments of the present invention has at least the following beneficial effects:

[0015] The flexible substrate possesses high elasticity, thereby ensuring the flexible electronic film exhibits electrical stability that allows for repeated stretching. This, in turn, ensures that the functional film can adapt to the significant deformation caused by the contraction and expansion of the balloon body.

[0016] The biodegradable spun layer provided by this invention not only encapsulates the conductive circuit to prevent it from being scratched, but also has a loose and porous structure to load more drugs, while allowing electric fields to pass through; thereby enabling the rapid release of the drugs and stimulating the cells to rapidly absorb drugs such as paclitaxel through electroosmosis, achieving better therapeutic effects.

[0017] After use, the functional membrane can be washed off with organic solvents such as ethanol, thus completing the recycling of the balloon body.

[0018] In summary, the drug-eluting electronic balloon provided by this invention, through structural and material design, can significantly improve the loading capacity of drugs such as paclitaxel, enhance the mechanical adaptability of the balloon body and functional membrane, increase the uptake of drugs such as paclitaxel in the stenotic portion of the blood vessel per unit time (high delivery efficiency), improve the treatment effect of vascular stenosis, and the balloon body can be reused, saving costs.

[0019] According to some embodiments of the present invention, the pattern of the conductive circuit includes an interdigitated electrode pattern. This allows for the balance of electric field uniformity in the conductive circuit, precise stimulation localization, and control of the number of wires, ultimately achieving efficient and stable electrical stimulation.

[0020] According to some embodiments of the present invention, the conductive circuit includes liquid metal.

[0021] According to some embodiments of the present invention, the liquid metal comprises a gallium-indium alloy.

[0022] According to some embodiments of the present invention, the flexible substrate material includes at least one selected from polyurethane, polyvinyl butyral, nitrocellulose, and cellulose acetate butyrate. Films made from these materials all possess high flexibility and high tensile elasticity, allowing the resulting flexible substrate to maintain its integrity and good mechanical properties after repeated stretching and contraction.

[0023] According to some embodiments of the present invention, the flexible substrate is alcohol-soluble; specifically, it can be an alcohol-soluble polyurethane. This allows the functional film to be removed by alcohol washing after the drug delivery balloon has been used, enabling the balloon body to be reused.

[0024] According to some embodiments of the present invention, the thickness of the flexible electronic film is 10–30 μm. Specifically, it can be approximately 15 μm, 20 μm, or approximately 25 μm. The thickness of the flexible electronic film directly affects the adhesion effect between the functional film and the balloon body; within the above thickness range, under the action of van der Waals forces, the functional film is more likely to adhere to the surface of the balloon body. However, if the flexible electronic film is too thick, the size of the balloon body adapted to the blood vessel diameter, combined with the thick functional film, will result in an excessively large overall size of the resulting drug-eluting balloon, increasing pressure on the blood vessel. Simultaneously, this thickness also affects its ability to pass through the catheter sheath; excessive thickness can lead to difficulty in sheath insertion, making delivery via interventional surgery challenging.

[0025] According to some embodiments of the present invention, the biodegradable spun layer is made of at least one of polylactic acid-caprolactone, polylactic acid, polycaprolactone, polyglycolic acid, and polylactic acid-glycolic acid copolymer. These polymers have similar biocompatibility and mechanical properties.

[0026] According to some embodiments of the present invention, the biodegradable spun layer is made of polylactic acid-caprolactone. This material, combined with a specific spinning diameter, can achieve a Young's modulus similar to that of vascular tissue, thereby reducing vascular damage due to mechanical mismatch.

[0027] According to some embodiments of the present invention, the diameter of the spun fibers in the biodegradable spinning layer is between 0.5 and 3.0 μm. Specifically, it can be 0.8 μm, 1 μm, 1.2 μm, 1.4 μm, 1.6 μm, 1.8 μm, 2.0 μm, 2.2 μm, 2.5 μm, 2.8 μm, or a range consisting of any two of the above values.

[0028] According to some embodiments of the present invention, the drug loading in the drug functional layer is 0.15–0.25 mg / cm³. 2 For example, it could be 0.2 mg / cm³. 2 0.22 mg / cm 2 , or the range of values ​​formed by any two of the above point values.

[0029] According to some embodiments of the present invention, the drug in the drug functional layer includes at least one of paclitaxel, rapamycin, and aspirin. In actual use, a suitable drug can be selected according to needs; paclitaxel is commonly used, but the present invention does not impose strict limitations.

[0030] According to some embodiments of the present invention, the balloon body has a catheter; the catheter is connected to a power source via a wire. The wire comprises a copper wire; the diameter of the copper wire is 0.05 to 0.1 mm; specifically, it can be about 0.08 mm.

[0031] According to an embodiment of a second aspect of the present invention, a method for preparing the drug-eluting electronic balloon described in the first aspect of the present invention is provided, the method comprising the following steps:

[0032] S1. A first water-soluble sacrificial layer, conductive lines, and a flexible substrate are sequentially disposed on a first substrate;

[0033] The first water-soluble sacrificial layer is dissolved, and the resulting flexible electronic thin film is transferred onto a second substrate having a second water-soluble sacrificial layer, with the conductive lines facing away from the second substrate.

[0034] S2. In the component obtained in step S1, the biodegradable spun layer is spun on one side surface of the conductive circuit;

[0035] S3. Dissolve the second water-soluble sacrificial layer and transfer the resulting film onto the surface of the balloon body, with the flexible substrate side of the resulting film in contact with the balloon body;

[0036] S4. Load the drug into the biodegradable spinning layer.

[0037] Since the preparation method adopts all the technical solutions of the drug electronic balloon of the above embodiments, it has at least all the beneficial effects brought about by the technical solutions of the above embodiments.

[0038] This invention employs electrospinning technology in the preparation of the biodegradable spun layer. This technology can fabricate ultrafine fiber networks with diameters ranging from a few nanometers to tens of micrometers. By changing the applied voltage parameters, fiber networks of different diameters can be prepared. Lower diameters correspond to higher specific surface areas, allowing for the loading of more drugs. Furthermore, electrospinning technology can also be used to prepare ultrathin functional films on a large scale and in large quantities.

[0039] According to some embodiments of the present invention, in step S1, the first substrate and the second substrate are PET (polyethylene terephthalate).

[0040] According to some embodiments of the present invention, in step S1, the materials of the first and second water-soluble sacrificial layers include at least one of dextran, polyvinyl alcohol (PVA), and polyvinylpyrrolidone (PVP). In actual production, any material that can form a film and remains water-soluble after film formation is acceptable; no strict limitation is imposed here.

[0041] According to some embodiments of the present invention, in step S1, the method for setting the first water-soluble sacrificial layer and the second water-soluble sacrificial layer includes spin coating.

[0042] The slurry used is a 3-8% aqueous solution of dextran; the specific concentration can be about 5%.

[0043] The spin coating speed is 450-550 rpm; specifically, it can be about 500 rpm.

[0044] The spin coating time is 25-35 seconds; specifically, it can be about 30 seconds.

[0045] According to some embodiments of the present invention, in step S1, the conductive lines are arranged by screen printing.

[0046] The raw material for screen printing is liquid metal ink.

[0047] The method for synthesizing the liquid metallic ink is as follows: a liquid alloy and an organic solvent are ultrasonically mixed; the liquid alloy includes at least one of gallium-indium alloy, gallium metal, gallium-zinc alloy, and gallium-indium-tin alloy; the organic solvent includes at least one of n-decanol, ethanol, and N,N-dimethylformamide; the ultrasonic mixing is performed using an ultrasonic probe; the duration of ultrasonic mixing is 2–5 minutes; specifically, it can be approximately 3 minutes. Thus, the liquid alloy is dispersed into nanoparticles during the ultrasonic process, and its surface is oxidized to form an oxide layer, exhibiting a core-shell structure.

[0048] According to some embodiments of the present invention, in step S1, the method for setting the flexible substrate includes spin coating. Wherein,

[0049] The spin coating speed is 700-900 rpm; specifically, it can be about 800 rpm.

[0050] The spin coating time is 30 to 90 seconds; for example, it can be about 50 seconds, 60 seconds or about 70 seconds.

[0051] According to some embodiments of the present invention, in step S2, the spinning voltage is 5 to 20 kV. For example, it can be 5 kV, 8 kV, 10 kV, 12 kV, 15 kV, 18 kV, 20 kV; or a range of values ​​composed of any two of the above points.

[0052] According to some embodiments of the present invention, in step S4, the loading method includes spraying.

[0053] The raw material used for spraying is an aqueous solution of a drug;

[0054] The concentration of the aqueous solution of the drug is 0.8 to 1.2 mg / mL; for example, it can be about 1 mg / mL.

[0055] The spraying rate of the drug aqueous solution is 0.2–0.25 mL / cm². 2 .

[0056] The aqueous solution of the drug exhibits red fluorescence, thus its concentration and penetration depth in blood vessels can be observed through subsequent fluorescence testing.

[0057] According to an embodiment of a third aspect of the present invention, the application of the drug-eluting electronic balloon described in the first aspect of the present invention in the preparation of medical devices for coronary heart disease is provided.

[0058] Since the application employs all the technical solutions of the drug electronic balloon of the above embodiments, it has at least all the beneficial effects brought about by the technical solutions of the above embodiments.

[0059] Unless otherwise specified, the term "about" in this invention actually means that the error is allowed to be within ±2%, for example, about 100 is actually 100 ± 2% × 100.

[0060] Unless otherwise specified, "between" in this invention includes the number itself, for example, "between 2 and 3" includes the endpoint values ​​2 and 3.

[0061] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. Attached Figure Description

[0062] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which:

[0063] Figure 1 This is a schematic diagram of the preparation process of liquid metal ink in step S1 of Embodiment 1 of the present invention.

[0064] Figure 2 The diagram shows the design of the interdigitated conductive circuit in Embodiment 1 of the present invention (left) and the physical image of the resulting flexible electronic thin film (right).

[0065] Figure 3 This is a step diagram of water transfer printing in step S1d of embodiment 1 of the present invention.

[0066] Figure 4 This is a cross-sectional SEM image of the component obtained in step S1c of Embodiment 1 of the present invention.

[0067] Figure 5 This is a repeated stretching test diagram of the flexible electronic thin film obtained in Embodiment 1 of the present invention.

[0068] Figure 6 The image shows the design drawing (left) and the actual electron microscope test image (right) of the biodegradable spinning layer in step S2 of embodiment 1 of the present invention.

[0069] Figure 7 This is a statistical chart of the spinning diameter in the biodegradable spinning layer in Examples 1 to 4 of the present invention.

[0070] Figure 8This is a Young's modulus test diagram of the biodegradable spinning layer in Embodiment 1 of the present invention.

[0071] Figure 9 This is a step diagram of water transfer printing in step S3 of embodiment 1 of the present invention.

[0072] Figure 10 This is a schematic diagram (left) of the paclitaxel-loaded drug in step S4 of embodiment 1 of the present invention, and a physical image (right) of the resulting drug-loaded electronic balloon.

[0073] Figure 11 This is a schematic diagram of the extracorporeal circulation system in Test Example 2 of the present invention.

[0074] Figure 12 This is a graph showing the results of voltage magnitude and drug concentration in blood vessels in Test Example 2 of the present invention.

[0075] Figure 13 This is a tissue staining image of blood vessels with HE (hematoxylin and eosin) in Test Example 3 of this invention.

[0076] Figure 14 This is a statistical chart of the results for different groups in Test Example 3 of this invention. Detailed Implementation

[0077] The following will describe the concept and technical effects of the present invention clearly and completely with reference to embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention.

[0078] Example 1

[0079] refer to Figures 1-4 In this example, a drug-eluting electronic balloon was prepared, and the specific steps are as follows:

[0080] S1. Preparation of flexible electronic thin films:

[0081] S1a. Spin-coating 5% water-soluble dextran onto polyethylene terephthalate (PET, first substrate) at 500 rpm for 30 s; forming the first water-soluble sacrificial layer;

[0082] S1b. Mix 3g of gallium-indium alloy (gallium:indium = 75:25 molar ratio) with 1mL of n-decanol and treat under ultrasonic probe for 3min. Due to its high surface tension, the gallium-indium alloy vibrates and breaks into spherical particles with diameters reaching the nanometer scale under the action of sound waves. During the preparation process, the surface of the gallium-indium alloy particles is slowly oxidized to form a gallium oxide shell (process as follows). Figure 1 (As shown), forming liquid metallic ink;

[0083] Design the circuit diagram using AutoCAD software, specifically as follows: Figure 2 The interdigitated electrode pattern shown on the left.

[0084] Screen printing conductive circuits: Interdigitated circuit patterns are engraved on a screen, forming a structure in which liquid metal ink is allowed to pass through only the patterned areas.

[0085] By moving the squeegee, liquid metallic ink is patterned into interdigitated conductive lines on the surface of the first water-soluble sacrificial layer.

[0086] S1c. Spin-coat a layer of alcohol-soluble polyurethane (APU) (flexible substrate) onto the surface of the conductive circuit at a speed of 800 rpm for 60 seconds (see the image of the resulting product). Figure 2 (As shown in the right figure). The slurry used had a solid content of 50% and was purchased from Jining Zhongjian Chemical Co., Ltd., model PU-3514.

[0087] The flexible electronic thin film, consisting of a flexible substrate and conductive circuitry, has a thickness of approximately 25 μm. The thickness was measured using scanning electron microscopy (SEM). Figure 4 As shown.

[0088] S1d. After drying the component obtained in step S1c, soak it in water. The first water-soluble sacrificial layer dissolves in the water, and the ultra-thin flexible electronic film floats and unfolds on the water surface due to the surface tension of the water. It is then transferred via water transfer to another PET substrate (second substrate) containing dextran (the second water-soluble sacrificial layer). After the transfer, the conductive lines face away from the second substrate (conductive lines facing upwards, exposed). The specific water transfer process is as follows... Figure 3 As shown.

[0089] S2. The designed structure and actual electron microscope image of the biodegradable spun layer prepared in this step are shown below. Figure 6 As shown.

[0090] First, we dissolved 10% polylactic acid-caprolactone (PLCL) in hexafluoroisopropanol to prepare a spinning solution, and then spun it onto the surface of a conductive circuit at a voltage of 15kV to obtain a biodegradable spun layer.

[0091] S3. Immerse the component obtained in step S2 in water. After the dextran (second water-soluble sacrificial layer) dissolves in water, a composite film is released. This film is then conformally attached to the surface of the balloon body (Abbott coronary balloon dilation catheter 1012447-15) via water transfer printing (process as follows). Figure 9 As shown in the diagram, after the transfer, the biodegradable spun layer is exposed (away from the balloon matrix). The balloon body used in this example has a conduit.

[0092] S4. Finally, a paclitaxel solution (PTX-Cy5, 1 mg / mL, red fluorescence) dissolved in deionized water is uniformly sprayed onto the surface of the biodegradable spun layer by spraying at a rate of 0.21 mL / cm². 2 The schematic diagram and the resulting physical diagram for this step are as follows: Figure 10 As shown.

[0093] After the above steps are completed, a 0.08mm copper wire is wound around the conduit, and the other end of the copper wire is connected to an external power source to provide power during use.

[0094] Example 2

[0095] This example demonstrates the preparation of a drug-eluting electronic balloon, which differs from Example 1 in that:

[0096] In step S2, the voltage for electrospinning is 5kV.

[0097] Example 3

[0098] This example demonstrates the preparation of a drug-eluting electronic balloon, which differs from Example 1 in that:

[0099] In step S2, the voltage for electrospinning is 10kV.

[0100] Example 4

[0101] This example demonstrates the preparation of a drug-eluting electronic balloon, which differs from Example 1 in that:

[0102] In step S2, the voltage for electrospinning is 20kV.

[0103] Comparative Example

[0104] This example demonstrates the preparation of a drug-eluting electronic balloon, which differs from Example 1 in that:

[0105] Steps S1 to S4 are excluded; the paclitaxel solution is directly sprayed onto the balloon body.

[0106] Test Example 1

[0107] The first aspect of this example tested the repeatable stretch stability of the flexible electronic film obtained in step S1 of Example 1. Specifically, the flexible electronic film was fixed to a cyclically stretchable guide rail using a clamp and stretched tens of thousands of times. The film was connected to a resistance meter for real-time recording. Each stretch was performed by 100% of the original distance; for example, if the initial stretch was 5mm, the maximum stretch distance was 10mm. The test results showed that within the operational range of the drug-eluting electronic balloon, after tens of thousands (approximately 80,000) of repeated stretching, the voltage of the flexible electronic film remained stable within a certain range. This indicates that, benefiting from the shrinkability of polyurethane, the obtained flexible electronic film exhibits good electrical stability. Specific test results are as follows: Figure 5 As shown.

[0108] The second aspect of this example tested the spinning diameter in the biodegradable spun layer obtained in step S2 of Examples 1-4. The specific testing method was as follows: the spinning diameter was statistically analyzed by taking scanning electron microscope (SEM) images. The results showed that when the spinning voltage was 5 kV, the spinning diameter was distributed between 2 and 3 μm; when the spinning voltage was 10 kV, the spinning diameter was distributed between 1.25 and 2 μm; when the spinning voltage was 15 kV, the spinning diameter was distributed between 0.2 and 1.2 μm; and when the spinning voltage was 20 kV, the spinning diameter was distributed between 1.25 and 2 μm. Specific test results are as follows: Figure 7 As shown. Since a low diameter corresponds to a high specific surface area, it can load more drugs; therefore, subsequent performance verifications were all performed using the drug-eluting electronic balloon obtained in Example 1. However, it is known that although the performance of other embodiments is slightly worse (mainly in terms of drug loading capacity and drug loading uniformity), good data transmission results can still be achieved.

[0109] The third aspect of this example tested the Young's modulus of the biodegradable spun layer obtained in Example 1. The specific testing method was as follows: the Young's modulus was measured by stretching using a universal testing instrument. The test results showed that the biodegradable spun layer has a Young's modulus similar to that of vascular tissue, which can reduce vascular damage caused by mechanical mismatch. Specific test results are as follows: Figure 8 As shown.

[0110] Test Example 2

[0111] In this example, the in vitro testing of the drug-eluting electronic balloon obtained in Example 1 promoted drug absorption by vascular cells. The specific testing method is as follows:

[0112] The abdominal aorta (blood vessel) isolated from SD rats was used as the electrical stimulation target. An extracorporeal circulation system was constructed using a peristaltic pump, the specific components of which are as follows: Figure 11As shown. Electrical stimulation was applied to the drug delivery balloon using an external power supply (UDP33025s DC regulated power supply) to evaluate its promoting effect on drug delivery. During the test, the pressure on the abdominal aorta was consistent with the pressure on the blood vessels inside the body, approximately between 85-115 mmHg.

[0113] Because the interdigitated conductive circuitry used in the electronic balloon can create a stable, intersecting electric field, and given the need for continuous, stable electric field drug delivery in atherosclerosis treatment, direct current stimulation was chosen in this case. The optimal stimulation parameters were screened within a safe human voltage range (less than 36V) to provide a basis for subsequent in vivo animal experiments. The stimulation device was connected to the electronic balloon system, ensuring close contact between the outer wall of the drug-eluting balloon and the blood vessel wall. The stimulation parameters were set as follows: voltage range of 0–20V, duration of 1 minute. Different voltage values ​​were tested to screen for the optimal stimulation parameters. After stimulation, saline was circulated in the extracorporeal circulation system for 10 minutes to ensure sufficient drug penetration into the blood vessel wall.

[0114] After electrical stimulation, the vascular segment was removed from the extracorporeal circulation system, rinsed thoroughly with saline to remove any residual drug solution from the surface, and then immobilized in 4% paraformaldehyde for 1 hour.

[0115] The fixed vascular segment was cut into 5 μm thick sections using a cryostat (Leica CM1950, Leica Microsystems, Germany) and placed on glass slides. Fluorescence labeling in the sections was observed using a fluorescence microscope (NIKON, A1). The excitation wavelength was set to 633 nm, and the emission wavelength to 650–700 nm to detect the fluorescence signal of PTX-Cy5. Fluorescence images were captured at different voltages and analyzed to assess the drug distribution in the vascular wall. Fluorescence intensity was directly proportional to the depth and concentration of drug penetration. The results showed that the fluorescence intensity was highest at a voltage around 10 V, indicating the highest drug penetration depth and concentration; this also demonstrated the therapeutic effect of direct current stimulation. Specific test results are as follows: Figure 12 As shown. A voltage of 10V was selected as the electrical stimulation parameter for subsequent animal experiments.

[0116] Test Example 3

[0117] This example demonstrates an in vivo animal study of the drug-eluting electronic balloon obtained in Example 1 to verify its therapeutic effect on atherosclerosis. The specific method is as follows:

[0118] A coronary artery stenosis model was established using healthy male New Zealand white rabbits (weighing 2.8–3.2 kg, aged 4–5 months). The model was constructed using a high-fat diet combined with vascular injury. Eight weeks prior to surgery, rabbits were given a customized diet (formula: 1.5% cholesterol, 15% lard, 0.5% sodium cholate), with a daily intake controlled at 150 g / rabbit. At week 6, under general anesthesia (midazolam 0.5 mg / kg + fentanyl 10 μg / kg), balloon injury of the left anterior descending artery was performed via the femoral artery: a 2.5 mm × 15 mm non-compliant balloon was used, inflated three times at 8 atm, each time lasting 30 seconds, with a 2-minute interval. A high-fat diet was continued for two weeks post-surgery to promote plaque formation.

[0119] The experimental group (electro-assisted balloon group) received paclitaxel-treated electro-assisted balloon therapy at week 9 after successful modeling, with a direct current of 10V applied for 1 minute. The untreated group underwent only conventional balloon dilation; a separate untreated balloon group was also set up, the difference from the experimental group being that no direct current was applied.

[0120] Postoperative evaluation used optical coherence tomography (OCT) and tissue sections to assess the area of ​​restenosis and intimal hyperplasia, and to verify the therapeutic effect of the electronic drug-eluting balloon.

[0121] The results showed that plaque formation was indeed present on the vascular wall in the first control group, indicating successful modeling, and that the plaque would not disappear automatically without intervention. The second control group did show some degree of delay in arterial stenosis, but the arterial wall remained relatively thick. The experimental group, using a drug-eluting electronic balloon combined with electrical stimulation, not only temporarily delayed arterial stenosis but also eliminated some degree of arterial wall hyperplasia, fundamentally resolving the problem of arterial stenosis. Specific test results are as follows: Figure 13 As shown; the short black line in the figure represents a scale, representing a length of 200μm.

[0122] The percentage of narrowed areas and the area of ​​newly proliferating endometrium in the three groups showed that the experimental group had a significant advantage and was statistically significantly different from the other two groups. The statistical results are as follows: Figure 14 As shown.

[0123] The embodiments of the present invention have been described in detail above with reference to the accompanying drawings. However, the present invention is not limited to the above embodiments, and various changes can be made within the scope of knowledge possessed by those skilled in the art without departing from the spirit of the present invention. Furthermore, the embodiments of the present invention and the features thereof can be combined with each other unless otherwise specified.

Claims

1. A drug eluting electronic balloon, characterized in that, The drug electronic balloon comprises a balloon body and a functional film attached to the balloon body; The functional film comprises a flexible electronic film and a drug functional layer stacked from the balloon body; The flexible electronic film comprises a flexible substrate and a conductive circuit embedded in the flexible substrate; the conductive circuit is in contact with the drug functional layer; The drug functional layer comprises a biodegradable spinning layer and a drug loaded in the biodegradable spinning layer.

2. The drug eluting balloon according to claim 1, characterized in that The thickness of the flexible electronic film is 10-30 μm; and / or the material of the flexible substrate comprises at least one of polyurethane, polyvinyl butyral, nitrocellulose and cellulose acetate butyrate.

3. The drug eluting balloon of claim 1, wherein, The pattern of the conductive circuit comprises an interdigital electrode pattern; and / or the conductive circuit comprises a liquid metal.

4. The drug eluting balloon of claim 1, wherein, The material of the biodegradable spinning layer comprises at least one of polylactic acid-caprolactone, polylactic acid, polycaprolactone, polyglycolic acid and poly(lactic-co-glycolic acid); and / or the diameter of the spinning is 0.5-3.0 μm.

5. The drug eluting balloon according to any one of claims 1 to 4, characterized in that, The drug functional layer has a drug loading amount of 0.15-0.25 mg / cm 2 ; and / or the drug includes at least one of paclitaxel, rapamycin, and aspirin.

6. A method of manufacturing a drug eluting balloon according to any one of claims 1 to 5, characterized in that, The preparation method comprises the following steps: S1. sequentially arranging a first water-soluble sacrificial layer, a conductive circuit and a flexible substrate on a first substrate; dissolving the first water-soluble sacrificial layer and transferring the obtained flexible electronic film to a second substrate with a second water-soluble sacrificial layer, the conductive circuit facing away from the second substrate; S2. spinning the biodegradable spinning layer on the surface of the conductive circuit of the component obtained in step S1; S3. dissolving the second water-soluble sacrificial layer and transferring the obtained film to the surface of the balloon body, the surface of the flexible substrate of the obtained film being in contact with the balloon body; S4. loading the drug in the biodegradable spinning layer.

7. The preparation method according to claim 6, characterized in that, In step S1, the material of the first water-soluble sacrificial layer and the second water-soluble sacrificial layer comprises at least one of dextran, polyvinyl alcohol and polyvinylpyrrolidone.

8. The preparation method according to claim 6, characterized in that, In step S1, the conductive circuit is arranged by screen printing; and / or in step S1, the flexible substrate is arranged by spin coating.

9. The preparation method according to claim 6, characterized in that, In step S2, the voltage for spinning is 5-20 kV; and / or in step S4, the loading method comprises spraying.

10. Use of the drug electronic balloon according to any one of claims 1-5 in the preparation of a drug device for coronary heart disease.

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