Aortic dissection treatment drug delivery device based on double-layer balloon

Abstract

The invention relates to the field of medical instruments, and discloses an aortic dissection treatment drug delivery device based on a double-layer balloon, the aortic dissection treatment drug delivery device comprises an outer balloon, a blood vessel repair coating is arranged on the outer wall of the outer balloon, injection structures are uniformly arranged on one side of the outer balloon, and a catheter structure is fixedly arranged in the middle of the outer balloon. A catheter seat is fixedly arranged at one end of the catheter structure, an inner balloon is fixedly arranged at the other end of the catheter structure, the inner balloon is located in an outer balloon, drug gel is arranged between the inner balloon and the outer balloon, and a medical protective sleeve is arranged in the catheter structure. The device is conveyed through the catheter structure and the guide wire, and in the conveying process of the device, the vascular repair coating and the drug gel can only generate activation reaction and viscidity fixation under the action of light, so that the vascular repair coating and the drug gel do not react under the condition of no light emission, and the integrity and effectiveness of the drug are ensured.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and specifically to an aortic dissection treatment drug delivery device based on a double-layer balloon. Background Art

[0002] The technical field of medical devices is constantly evolving, aiming to develop more efficient, safe and innovative treatment devices to address various disease challenges, which is particularly crucial in the field of aortic dissection treatment. As a critical and severe disease in the cardiovascular field, aortic dissection seriously threatens the life and health of patients. Its pathogenesis mainly stems from the tearing of the aortic intima, causing blood to rush into the media layer, forming a separation of true and false lumens. The development of the false lumen can compress the true lumen, hinder blood flow, and cause organ ischemia. The risk of thrombosis and blood vessel rupture in the false lumen is also extremely high.

[0003] Traditional drug delivery devices are mostly balloons and catheters, with drugs loaded on their outer walls and sent to the aortic dissection site for drug delivery. However, after the balloon or catheter enters the body, it does not immediately start drug release to exert a therapeutic effect. Instead, it needs to go through a variable transportation and difficult correction operation process to achieve precise positioning. The contact between the drugs on its surface and blood vessels or natural channels will inevitably trigger drug release and corrosion, and it is more likely to exacerbate drug disintegration in a curved and narrow transportation path, resulting in the formation of large particles and sharp-edge shedding substances on the initial drug coating, which not only weakens the treatment effect but also increases the risk of systemic adverse reactions, restricting the safety and effectiveness of treatment. Summary of the Invention

[0004] Aiming at the deficiencies of the prior art, the present invention provides an aortic dissection treatment drug delivery device based on a double-layer balloon, which solves the problem that after the traditional drug delivery device enters the human body, the contact between the drugs on its surface and blood vessels or natural channels will inevitably trigger drug release and corrosion, and it is more likely to exacerbate drug disintegration in a curved and narrow transportation path, resulting in the formation of large particles and sharp-edge shedding substances on the initial drug coating, which not only weakens the treatment effect but also increases the risk of systemic adverse reactions, restricting the safety and effectiveness of treatment.

[0005] To achieve the above object, the present invention is realized by the following technical solutions: A drug delivery device for treating aortic dissection based on a double-layer balloon, including an outer balloon, the outer wall of the outer balloon is provided with a vascular repair coating, the outer balloon is evenly provided with injection structures on one side, a catheter structure is fixedly arranged in the middle of the outer balloon, one end of the catheter structure is fixedly provided with a catheter seat, the other end of the catheter structure is fixedly provided with an inner balloon, the inner balloon is located inside the outer balloon, a drug gel is arranged between the inner balloon and the outer balloon, a medical protective sleeve is arranged inside the catheter structure, a cladding sleeve is fixedly connected inside the medical protective sleeve, an optical fiber is fixedly connected inside the cladding sleeve, one end of the optical fiber is fixedly provided with a microlens, the microlens is located inside the inner balloon, the microlens is used for emitting light to the vascular repair coating and the drug gel, the vascular repair coating is used for activating a reaction under the action of light, and the drug gel is used for activating a reaction and sticky fixation under the action of light.

[0006] Preferably, the catheter structure includes a first catheter, the outer wall of the first catheter is evenly provided with fourth catheters, a second catheter is arranged inside the first catheter, and a third catheter is arranged inside the second catheter. One ends of the first catheter, the second catheter, and the third catheter are fixedly arranged on one side of the catheter seat.

[0007] Preferably, the other ends of the second catheter and the third catheter are fixedly arranged in the middle of the inner balloon, the other end of the first catheter is fixedly arranged in the middle of the outer balloon, and a one-way valve is arranged between the first catheter and the second catheter, and the one-way valve is located inside one end of the first catheter.

[0008] Preferably, the fourth catheter is used to guide the blood flow of the aorta, the gap between the second catheter and the third catheter is communicated with the inside of the inner balloon, and the gap between the first catheter and the second catheter is communicated with the gap between the outer balloon and the inner balloon.

[0009] Preferably, the inside of the injection structure is communicated with the inside of the outer balloon, a cavity is arranged in the middle of the catheter seat, the inside of the cavity is communicated with the inside of the third catheter, and one side of the medical protective sleeve is arranged inside the third catheter.

[0010] Preferably, the catheter seat is evenly provided with first balloon filling ports inside, the inside of the first balloon filling ports is communicated with the gap between the second catheter and the third catheter, the catheter seat is evenly provided with second balloon filling ports inside, and the inside of the second balloon filling ports is communicated with the gap between the first catheter and the second catheter.

[0011] Vascular repair coating, comprising raw materials in the following parts by weight: 15-25 parts of vascular endothelial growth factor, 10-20 parts of fibroblast growth factor, 15-25 parts of pentaerythritol tetraacrylate, 10-20 parts of dipropylene glycol diacrylate, 30-45 parts of chitosan, and 25-40 parts of hyaluronic acid.

[0012] Preparation method of the vascular repair coating, comprising the following steps:

[0013] S1. Raw material pretreatment: Dissolve vascular endothelial growth factor in a phosphate buffer solution at 4°C containing 0.1% bovine serum albumin to prepare a vascular endothelial growth factor solution with a concentration of 1-5 mg / mL. Dissolve fibroblast growth factor in PBS containing 0.1% human serum albumin to form a fibroblast growth factor solution with a concentration of 1-5 mg / mL. Prepare a pentaerythritol tetraacrylate solution and a dipropylene glycol diacrylate solution with concentrations of 50-100 mg / mL respectively by dissolving pentaerythritol tetraacrylate and dipropylene glycol diacrylate in acetone. Dissolve chitosan in a 1% acetic acid solution, adjust the concentration to a chitosan solution of 50-100 mg / mL, and stir until transparent. Dissolve hyaluronic acid in deionized water to prepare a hyaluronic acid solution with a concentration of 50-100 mg / mL;

[0014] S2. Solution mixing: Then, add the vascular endothelial growth factor solution and the fibroblast growth factor solution to a sterile container according to parts by weight, stir on a magnetic stirrer at a speed of 100-200 rpm for 10-15 minutes, then add the pentaerythritol tetraacrylate solution and the dipropylene glycol diacrylate solution, increase the stirring speed to 300-400 rpm, continue stirring for 20-30 minutes, then add the chitosan solution and the hyaluronic acid solution, and stir at a speed of 400-500 rpm for 30-45 minutes to form a uniform mixed solution. During the stirring process, the container is placed in an ice bath;

[0015] S3. Solution coating: Immerse the outer balloon in the mixed solution, lift it at a speed of 5-10 cm / min to uniformly coat the coating on its surface, repeat the dipping coating 2-3 times, and after each dipping coating, place it in a fume hood;

[0016] S4. Photocuring: Use an ultraviolet light source with a wavelength of 400-500 nm to irradiate the coated outer balloon, control the light intensity at 20-50 mW / cm 2 , and the irradiation time is 60-120 seconds to cause a cross-linking reaction initiated by a photoinitiator to form a vascular repair coating.

[0017] Drug gel, comprising raw materials in the following parts by weight: 30 - 40 parts of collagen, 15 - 25 parts of fibronectin, 5 - 10 parts of benzoin dimethyl ether, 3 - 8 parts of benzophenone, 10 - 15 parts of rapamycin, 8 - 12 parts of sirolimus, 12 - 20 parts of heparin, and 8 - 15 parts of urokinase.

[0018] Preparation method of the drug gel, comprising the following steps:

[0019] S1. Pretreatment: Dissolve collagen in a 0.05M acetic acid solution at 4°C with stirring to prepare a collagen solution with a concentration of 50 - 100 mg / mL. Dissolve fibronectin in PBS containing 0.1% human serum albumin to form a fibronectin solution with a concentration of 20 - 50 mg / mL. Dissolve benzoin dimethyl ether and benzophenone in ethanol respectively to form a benzoin dimethyl ether solution and a benzophenone solution with a concentration of 20 - 50 mg / mL. Dissolve rapamycin and sirolimus in dimethyl sulfoxide to form a rapamycin solution and a sirolimus solution with a concentration of 10 - 30 mg / mL. Dissolve heparin in physiological saline to prepare a heparin solution with a concentration of 50 - 100 mg / mL. Dissolve urokinase in a Tris-HCl buffer solution with a pH of 7.2 - 7.4 to form a urokinase solution with a concentration of 20 - 50 mg / mL.

[0020] S2. Mixing: Then mix the collagen solution and the fibronectin solution by weight in a sterile container, stir with a magnetic stirrer at a speed of 100 - 200 rpm for 10 - 15 minutes, then add the benzoin dimethyl ether solution and the benzophenone solution, increase the stirring speed to 300 - 400 rpm, stir for 20 - 30 minutes, then add the rapamycin solution and the sirolimus solution, continue to stir for 20 - 30 minutes, keep the stirring speed at 300 - 400 rpm, then add the heparin solution and the urokinase solution, stir at a speed of 400 - 500 rpm for 30 - 45 minutes, and during the stirring process, the whole container needs to be placed in an environment of 4 - 8°C to form a drug gel solution.

[0021] S3. Molding: Then inject the drug gel solution into a sterile mold and freeze it in an environment of -20°C for 2 - 4 hours to form the drug gel.

[0022] Working principle: During use, the device is delivered through the catheter structure and guide wire. During the delivery of the device, since the vascular repair coating and the drug gel can only undergo activation reaction and adhesive fixation under the action of light, they will not react in the absence of light emission. When the device is delivered to the aortic dissection, the space between the second catheter and the third catheter is filled through the first balloon filling port, thereby filling the interior of the inner balloon, causing the inner balloon to expand, and then driving the outer balloon to expand through the expansion of the inner balloon, fixing the device at the aortic dissection, making the vascular repair coating fit with the aorta, and at the same time, the fourth catheter guides the blood flow in the aorta.

[0023] Moreover, through the expansion of the outer balloon, the injection structure on its surface penetrates into the aortic dissection as it expands. Then, the drug gel is sent into the interior of the outer balloon through the space between the first catheter and the second catheter through the second balloon filling port, enabling the drug gel to move into the aortic dissection through the injection structure. At the same time, the microlens receives the optical signal through the optical fiber and emits light to the vascular repair coating and the drug gel, causing the vascular repair coating to undergo an activation reaction under the action of light, promoting the repair of the damaged blood vessel wall. The one-way valve prevents the drug gel from entering the first catheter, enabling it to move towards the aortic dissection under the pressure exerted by the expansion of the inner balloon. It undergoes an activation reaction and adhesive fixation under the action of light, thereby achieving local drug delivery to the aortic dissection.

[0024] The present invention provides an aortic dissection treatment and drug delivery device based on a double-layer balloon. It has the following

[0025] Beneficial effects:

[0026] 1. The present invention delivers the device through the catheter structure and guide wire. During the delivery of the device, since the vascular repair coating and the drug gel can only undergo activation reaction and adhesive fixation under the action of light, they will not react in the absence of light emission, ensuring the integrity and effectiveness of the drug, avoiding the weakening of the treatment effect caused by the premature release of the drug, and avoiding the release and corrosion of the drug during the delivery process, which may lead to the formation of large particles and sharp-edge shedding of the initial drug coating.

[0027] 2. The present invention fills the outer balloon through the second balloon filling port, fixes the device at the aortic dissection site, fills the inner balloon through the first balloon filling port, and the microlens receives the optical signal through the optical fiber to emit light to the vascular repair coating and the drug gel, so that the vascular repair coating undergoes an activation reaction under the action of light, promoting the repair of the damaged vascular wall. The drug gel moves to the aortic dissection site through the injection structure by the expansion of the inner balloon, and it undergoes an activation reaction and viscous fixation under the action of light, delivering the drug accurately to the lesion site of the aortic dissection, achieving local treatment and reducing systemic adverse reactions.

[0028] 3. The outer wall of the outer balloon of the present invention is provided with a vascular repair coating. Under the action of light, pentaerythritol tetraacrylate and dipropylene glycol diacrylate act as photoinitiators for crosslinking reaction, and at the same time other active ingredients play a role in promoting vascular repair, thus realizing the activation reaction of the vascular repair coating under the action of light, promoting the repair of the damaged vascular wall, enhancing the stability of the vascular wall, and reducing the risk of further development of the dissection.

[0029] 4. The expansion of the inner balloon of the present invention enables the drug gel to move to the aortic dissection site through the injection structure of the outer balloon. Under the action of light, using benzoin dimethyl ether and benzophenone as photoinitiators, the drug gel undergoes an activation reaction and viscous fixation under the action of light, and at the same time other drug components play their respective therapeutic roles, thereby performing local drug delivery to the aortic dissection, improving the utilization efficiency of the drug, reducing the adverse effects of the drug on other parts of the body, concentrating efforts on treating the aortic dissection, enhancing the treatment effect while ensuring the medication safety of the patient. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 is a perspective view of the present invention;

[0031] Figure 2 is a schematic diagram of the internal structure of the inner balloon of the present invention;

[0032] Figure 3 is Figure 2 an enlarged view of part A in

[0033] Figure 4 is a schematic diagram of the partial structure of the medical protective sheath of the present invention;

[0034] Figure 5 is Figure 4 an enlarged view of part B in

[0035] Figure 6 is a schematic diagram of the partial structure of the catheter seat of the present invention;

[0036] Figure 7 is a schematic diagram of the inside of the catheter seat of the present invention;

[0037] Figure 8 Flow chart of the preparation method of the vascular repair coating of the present invention;

[0038] Figure 9 Flow chart of the preparation method of the drug gel of the present invention.

[0039] Wherein, 1. outer balloon; 2. vascular repair coating; 3. injection structure; 4. first catheter; 5. catheter seat; 6. inner balloon; 7. microlens; 8. medical protective sheath; 9. second catheter; 10. third catheter; 11. cladding sleeve; 12. optical fiber; 13. first balloon filling port; 14. second balloon filling port; 15. cavity; 16. one-way valve; 17. drug gel; 18. fourth catheter. Detailed implementation manners

[0040] Next, the technical solutions of the present invention will be clearly and completely described in conjunction with the drawings of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without making creative efforts belong to the scope of protection of the present invention.

[0041] Embodiment:

[0042] Please refer to the attached Figure 1 - attached Figure 7 , an aortic dissection treatment drug delivery device based on a double-layer balloon provided by an embodiment of the present invention includes an outer balloon 1, a vascular repair coating 2 is provided on the outer wall of the outer balloon 1, an injection structure 3 is evenly arranged on one side of the outer balloon 1, a catheter structure is fixedly arranged in the middle of the outer balloon 1, one end of the catheter structure is fixedly provided with a catheter seat 5, the other end of the catheter structure is fixedly provided with an inner balloon 6, the inner balloon 6 is located inside the outer balloon 1, a drug gel 17 is arranged between the inner balloon 6 and the outer balloon 1, a medical protective sheath 8 is arranged inside the catheter structure, a cladding sleeve 11 is fixedly connected inside the medical protective sheath 8, an optical fiber 12 is fixedly connected inside the cladding sleeve 11, one end of the optical fiber 12 is fixedly provided with a microlens 7, the microlens 7 is located inside the inner balloon 6, the microlens 7 is used to emit light to the vascular repair coating 2 and the drug gel 17, the vascular repair coating 2 is used to undergo an activation reaction under the action of light, and the drug gel 17 is used to undergo an activation reaction and sticky fixation under the action of light.

[0043] The catheter structure includes a first catheter 4, a fourth catheter 18 is evenly arranged on the outer wall of the first catheter 4, a second catheter 9 is arranged inside the first catheter 4, a third catheter 10 is arranged inside the second catheter 9, and one ends of the first catheter 4, the second catheter 9, and the third catheter 10 are fixedly arranged on one side of the catheter seat 5.

[0044] The other end of the second catheter 9 and the third catheter 10 is fixedly arranged in the middle of the inner balloon 6, and the other end of the first catheter 4 is fixedly arranged in the middle of the outer balloon 1. A one-way valve 16 is arranged between the first catheter 4 and the second catheter 9, and the one-way valve 16 is located inside one end of the first catheter 4.

[0045] The fourth catheter 18 is used to guide the blood flow in the aorta. The gap between the second catheter 9 and the third catheter 10 is communicated with the inside of the inner balloon 6, and the gap between the first catheter 4 and the second catheter 9 is communicated with the gap between the outer balloon 1 and the inner balloon 6.

[0046] The inside of the injection structure 3 is communicated with the inside of the outer balloon 1. A cavity 15 is arranged in the middle of the catheter seat 5, and the inside of the cavity 15 is communicated with the inside of the third catheter 10. One side of the medical protective sleeve 8 is arranged inside the third catheter 10.

[0047] The inner part of the catheter seat 5 is evenly provided with a first balloon filling port 13, and the inside of the first balloon filling port 13 is communicated with the gap between the second catheter 9 and the third catheter 10. The inner part of the catheter seat 5 is evenly provided with a second balloon filling port 14, and the inside of the second balloon filling port 14 is communicated with the gap between the first catheter 4 and the second catheter 9.

[0048] Specifically, the device is sent to the aortic dissection through the catheter structure and the guide wire. The gap between the second catheter 9 and the third catheter 10 is filled through the first balloon filling port 13, so as to fill the inside of the inner balloon 6, so that the inner balloon 6 expands, and then drives the outer balloon 1 to expand through the expansion of the inner balloon 6, so as to fix the device at the aortic dissection, and at the same time make the vascular repair coating 2 fit with the aorta. The blood flow in the aorta is guided by the fourth catheter 18, and through the expansion of the outer balloon 1, the injection structure 3 on its surface penetrates into the aortic dissection as it expands.

[0049] The drug gel 17 is sent into the inside of the outer balloon 1 through the gap between the first catheter 4 and the second catheter 9 through the second balloon filling port 14. The microlens 7 receives the optical signal through the optical fiber 12 and emits light to the vascular repair coating 2 and the drug gel 17, so that the vascular repair coating 2 undergoes an activation reaction under the action of light, thereby promoting the repair of the damaged blood vessel wall, enhancing the stability of the blood vessel wall, reducing the risk of further development of the dissection, preventing the drug gel 17 from entering the first catheter 4 through the one-way valve 16, and making the drug gel 17 move into the aortic dissection through the injection structure 3. It undergoes an activation reaction and sticky fixation under the action of light, so as to perform local drug delivery to the aortic dissection, deliver the drug accurately to the diseased site of the aortic dissection, achieve local treatment, and reduce systemic adverse reactions.

[0050] During the transportation of the device, since the vascular repair coating 2 can only undergo an activation reaction under the action of light, and the drug gel 17 can only undergo an activation reaction and sticky fixation under the action of light, they will not react in the absence of light emission, thus avoiding the release and corrosion of drugs during transportation, which may lead to the formation of large particles and sharp-edge debris from the initial drug coating. This solves the problem that in traditional drug delivery devices, the contact between the surface drug and blood vessels or natural body cavities after entering the human body will inevitably trigger the release and corrosion of drugs, and the drug disintegration is more likely to be aggravated in curved and narrow delivery pathways, resulting in the formation of large particles and sharp-edge debris from the initial drug coating, which not only weakens the therapeutic effect but also increases the risk of systemic adverse reactions, restricting the safety and effectiveness of treatment.

[0051] The vascular repair coating comprises the following raw materials in parts by weight: 15 - 25 parts of vascular endothelial growth factor, 10 - 20 parts of fibroblast growth factor, 15 - 25 parts of pentaerythritol tetraacrylate, 10 - 20 parts of dipropylene glycol diacrylate, 30 - 45 parts of chitosan, and 25 - 40 parts of hyaluronic acid.

[0052] Specifically, by adding vascular endothelial growth factor, protease is stimulated to be produced by endothelial cells, which degrades the extracellular matrix, promotes the migration and proliferation of endothelial cells, and thus contributes to the repair and regeneration of damaged vascular endothelium.

[0053] By adding fibroblast growth factor, the activity of fibroblasts is stimulated, promoting the proliferation, differentiation, and synthesis of extracellular matrix by fibroblasts. During the vascular repair process, fibroblasts can synthesize extracellular matrix components such as collagen to strengthen the strength of the blood vessel wall.

[0054] By adding pentaerythritol tetraacrylate and dipropylene glycol diacrylate as photoinitiating crosslinking agents, under the action of light, pentaerythritol tetraacrylate and dipropylene glycol diacrylate respectively undergo crosslinking reactions, crosslink with other polymer chains to form a three-dimensional network structure, which helps to stabilize the structure of the vascular repair coating, enabling it to maintain good adhesion and stability on the blood vessel surface, and ensuring that the coating can firmly adhere to the blood vessel wall and is not easily detached.

[0055] By using chitosan, biocompatibility and antibacterial properties are provided. It has good biocompatibility and will not cause an immune response in the body. At the same time, chitosan itself has certain antibacterial activity, which can prevent the attachment and growth of bacteria on the surface of the vascular repair coating, reduce the risk of infection, and chitosan can interact with other components to enhance the overall performance of the coating.

[0056] By adding hyaluronic acid, the growth and differentiation environment of cells is regulated. Hyaluronic acid is an important component of the extracellular matrix, which can retain the moisture around cells, provide a moist environment for cells, facilitate cell growth and differentiation, and interact with other extracellular matrix components to regulate cell behavior, contributing to the smooth progress of the blood vessel repair process.

[0057] Through the synergistic action of these raw materials, when irradiated with light, pentaerythritol tetraacrylate and dipropylene glycol diacrylate act as photoinitiators for cross-linking reactions, while other active ingredients play a role in promoting blood vessel repair. Thus, the blood vessel repair coating undergoes an activation reaction under the action of light, promoting the repair of damaged blood vessel walls, enhancing the stability of blood vessel walls, and reducing the risk of further development of dissections.

[0058] Please refer to the attached Figure 8 , a method for preparing a blood vessel repair coating, comprising the following steps:

[0059] S1. Raw material pretreatment: Dissolve vascular endothelial growth factor in a phosphate buffer solution at 4°C containing 0.1% bovine serum albumin to prepare a vascular endothelial growth factor solution with a concentration of 1 - 5 mg / mL. Dissolve fibroblast growth factor in PBS containing 0.1% human serum albumin to form a fibroblast growth factor solution with a concentration of 1 - 5 mg / mL. Prepare a pentaerythritol tetraacrylate solution and a dipropylene glycol diacrylate solution with concentrations of 50 - 100 mg / mL respectively by dissolving pentaerythritol tetraacrylate and dipropylene glycol diacrylate in acetone. Dissolve chitosan in a 1% acetic acid solution, adjust the concentration to a chitosan solution of 50 - 100 mg / mL, and stir until transparent. Dissolve hyaluronic acid in deionized water to prepare a hyaluronic acid solution with a concentration of 50 - 100 mg / mL.

[0060] S2. Solution mixing: Then, add the vascular endothelial growth factor solution and the fibroblast growth factor solution to a sterile container by weight. Stir on a magnetic stirrer at a speed of 100 - 200 rpm for 10 - 15 minutes, then add the pentaerythritol tetraacrylate solution and the dipropylene glycol diacrylate solution, increase the stirring speed to 300 - 400 rpm, and continue stirring for 20 - 30 minutes. Then add the chitosan solution and the hyaluronic acid solution, and stir at a speed of 400 - 500 rpm for 30 - 45 minutes to form a uniform mixed solution. During the stirring process, the container is placed in an ice bath.

[0061] S3. Solution coating: Immerse the outer balloon 1 in the mixed solution, lift it at a speed of 5 - 10 cm / min to uniformly coat the coating on its surface, repeat the dipping coating 2 - 3 times, and after each dipping coating, place it in a fume hood.

[0062] S4. Photo-curing: The coated outer balloon 1 is irradiated with an ultraviolet light source having a wavelength of 400 - 500 nm, and the light intensity is controlled at 20 - 50 mW / cm 2 , and the irradiation time is 60 - 120 seconds to cause a cross-linking reaction by a photoinitiator cross-linking agent to form a vascular repair coating.

[0063] The following is a further introduction in combination with specific embodiments:

[0064] Example 1:

[0065] The vascular repair coating comprises the following raw materials in parts by weight: 25 parts of vascular endothelial growth factor, 20 parts of fibroblast growth factor, 25 parts of pentaerythritol tetraacrylate, 20 parts of dipropylene glycol diacrylate, 45 parts of chitosan, and 40 parts of hyaluronic acid.

[0066] The preparation method of the vascular repair coating comprises the following steps:

[0067] S1. Raw material pretreatment: The vascular endothelial growth factor is dissolved in a phosphate buffer solution at 4°C containing 0.1% bovine serum albumin to prepare a vascular endothelial growth factor solution with a concentration of 3 mg / mL. The fibroblast growth factor is dissolved in PBS containing 0.1% human serum albumin to form a fibroblast growth factor solution with a concentration of 3 mg / mL. Pentaerythritol tetraacrylate and dipropylene glycol diacrylate are respectively prepared into a pentaerythritol tetraacrylate solution and a dipropylene glycol diacrylate solution with a concentration of 70 mg / mL using acetone. Chitosan is dissolved in a 1% acetic acid solution, and the concentration is adjusted to a chitosan solution of 70 mg / mL and stirred until transparent. Hyaluronic acid is dissolved using deionized water to prepare a hyaluronic acid solution with a concentration of 70 mg / mL;

[0068] S2. Solution mixing: Then, the vascular endothelial growth factor solution and the fibroblast growth factor solution are added to a sterile container by weight, stirred on a magnetic stirrer at a speed of 150 rpm for 12.5 minutes, then the pentaerythritol tetraacrylate solution and the dipropylene glycol diacrylate solution are added, the stirring speed is increased to 350 rpm, and stirring is continued for 25 minutes. Then, the chitosan solution and the hyaluronic acid solution are added, and stirring is carried out at a speed of 450 rpm for 40 minutes to form a uniform mixed solution. During the stirring process, the container is placed in an ice bath;

[0069] S3. Solution coating: The outer balloon 1 is immersed in the mixed solution and pulled up at a speed of 7.5 cm / min to uniformly coat the coating on its surface. The dipping coating is repeated 2 times, and after each dipping coating, it is placed in a fume hood;

[0070] S4. Photo-curing: Use a UV light source with a wavelength of 450 nm to irradiate the coated outer balloon 1, control the light intensity at 35 mW / cm 2 , and the irradiation time is 90 seconds to cause the photoinitiator cross-linking agent to initiate a cross-linking reaction to form a vascular repair coating.

[0071] Example 2:

[0072] The difference between this example and the above Example 1 is:

[0073] The vascular repair coating includes the following raw materials in parts by weight: 15 parts of vascular endothelial growth factor, 10 parts of fibroblast growth factor, 15 parts of pentaerythritol tetraacrylate, 10 parts of dipropylene glycol diacrylate, 30 parts of chitosan, and 25 parts of hyaluronic acid.

[0074] Example 3:

[0075] The difference between this example and the above Example 1 is:

[0076] The vascular repair coating includes the following raw materials in parts by weight: 20 parts of vascular endothelial growth factor, 15 parts of fibroblast growth factor, 20 parts of pentaerythritol tetraacrylate, 15 parts of dipropylene glycol diacrylate, 37.5 parts of chitosan, and 32.5 parts of hyaluronic acid.

[0077] Table 1:

[0078] Comparison Example 1 Example 2 Example 3 Standard value Cell proliferation rate 95％ 75％ 85％ 60％ Coating adhesion 15 N / mm 8 N / mm 10 N / mm 8 N / mm Aging weight loss 10％ 20％ 15％ 50％

[0079] The comparison in the above table is for traditional vascular repair coatings. It can be seen from Table 1 that different amounts of vascular endothelial growth factor, fibroblast growth factor, pentaerythritol tetraacrylate, dipropylene glycol diacrylate, chitosan, and hyaluronic acid can affect the cell proliferation rate, coating adhesion, and aging weight loss of the vascular repair coating, thereby affecting the effectiveness and durability of the vascular repair coating, enhancing the performance stability of the vascular repair coating, enabling the vascular repair coating to be highly activated under the action of light, accurately acting on the lesion site, avoiding premature drug release and corrosion, and thus solving the problem that traditional vascular repair coatings cause drug release and corrosion when delivered through a balloon, weakening the treatment effect.

[0080] The drug gel includes the following raw materials in parts by weight: 30 - 40 parts of collagen, 15 - 25 parts of fibronectin, 5 - 10 parts of benzoin dimethyl ether, 3 - 8 parts of benzophenone, 10 - 15 parts of rapamycin, 8 - 12 parts of zotarolimus, 12 - 20 parts of heparin, and 8 - 15 parts of urokinase.

[0081] Specifically, the addition of collagen provides structural support for the drug gel. As one of the main components of the extracellular matrix, it can form a fibrous network structure, endowing the drug gel with certain strength and toughness, which helps to maintain the gel's shape in the body and can also serve as a carrier for other drug components.

[0082] The addition of fibronectin promotes cell adhesion. It can bind to receptors on the cell surface, guiding cell adhesion, migration, and proliferation on the gel, which helps to form a microenvironment conducive to tissue repair at the lesion site.

[0083] The addition of benzoin dimethyl ether and benzophenone serves as a photoinitiator. Under light irradiation, benzoin dimethyl ether and benzophenone generate free radicals, initiating the cross-linking reaction within the gel, transforming the drug gel from a liquid state to a solid state, achieving viscous fixation, and activating the drug release process, ensuring that the drug gel can be rapidly and stably activated and fixed under the action of light.

[0084] The addition of rapamycin and zotarolimus inhibits the excessive proliferation of vascular smooth muscle cells, the abnormal proliferation of vascular smooth muscle cells and intimal cells at the aortic dissection lesion site, prevents the excessive growth of vascular smooth muscle cells, reduces the risk of further development of the dissection, helps to maintain the stability of the vascular structure, and prevents complications such as restenosis.

[0085] The addition of heparin exerts an anticoagulant effect, inhibiting multiple links in the blood coagulation process, preventing thrombus formation, and ensuring smooth blood flow in the blood vessels.

[0086] The addition of urokinase achieves thrombolytic function. When small thrombi have formed at the lesion site, urokinase can activate the conversion of plasminogen to plasmin, and plasmin can degrade fibrin and dissolve the thrombus, restoring vascular patency.

[0087] Through the synergistic effect of these raw materials, under light irradiation, with benzoin dimethyl ether and benzophenone as photoinitiators, while other drug components exert their respective therapeutic effects, the drug gel undergoes an activation reaction and viscous fixation under the action of light, thereby performing local drug delivery for aortic dissection, precisely delivering the drug to the aortic dissection lesion site, achieving local treatment, and reducing systemic adverse reactions.

[0088] Please refer to the appendix Figure 9 , for the preparation method of the drug gel, which includes the following steps:

[0089] S1. Pretreatment: Stir and dissolve collagen in a 0.05 M acetic acid solution at 4°C to prepare a collagen solution with a concentration of 50 - 100 mg / mL. Dissolve fibronectin in PBS containing 0.1% human serum albumin to form a fibronectin solution with a concentration of 20 - 50 mg / mL. Dissolve benzoin dimethyl ether and benzophenone in ethanol respectively to form a benzoin dimethyl ether solution and a benzophenone solution with a concentration of 20 - 50 mg / mL. Dissolve rapamycin and sirolimus in dimethyl sulfoxide to form a rapamycin solution and a sirolimus solution with a concentration of 10 - 30 mg / mL. Dissolve heparin in physiological saline to prepare a heparin solution with a concentration of 50 - 100 mg / mL. Dissolve urokinase in a Tris-HCl buffer solution with a pH of 7.2 - 7.4 to form a urokinase solution with a concentration of 20 - 50 mg / mL;

[0090] S2. Mixing: Then mix the collagen solution and the fibronectin solution by weight in a sterile container, and use a magnetic stirrer to stir at a speed of 100 - 200 rpm for 10 - 15 minutes. Then add the benzoin dimethyl ether solution and the benzophenone solution, increase the stirring speed to 300 - 400 rpm, and stir for 20 - 30 minutes. Then add the rapamycin solution and the sirolimus solution, and continue to stir for 20 - 30 minutes with the stirring speed maintained at 300 - 400 rpm. Then add the heparin solution and the urokinase solution, and stir at a speed of 400 - 500 rpm for 30 - 45 minutes. During the stirring process, the entire container needs to be placed in an environment of 4 - 8°C to form a drug gel solution;

[0091] S3. Molding: Then inject the drug gel solution into a sterile mold and freeze it in an environment of -20°C for 2 - 4 hours to form a drug gel.

[0092] The following is a further introduction in combination with specific embodiments:

[0093] Example 4:

[0094] The drug gel comprises the following raw materials by weight: 30 - 40 parts of collagen, 15 - 25 parts of fibronectin, 5 - 10 parts of benzoin dimethyl ether, 3 - 8 parts of benzophenone, 10 - 15 parts of rapamycin, 8 - 12 parts of sirolimus, 12 - 20 parts of heparin, and 8 - 15 parts of urokinase.

[0095] The preparation method of the drug gel comprises the following steps:

[0096] S1. Pretreatment: Collagen is stirred and dissolved in a 0.05 M acetic acid solution at 4°C to prepare a collagen solution with a concentration of 50 - 100 mg / mL. Fibronectin is dissolved in PBS containing 0.1% human serum albumin to form a fibronectin solution with a concentration of 20 - 50 mg / mL. Benzoin dimethyl ether and benzophenone are respectively dissolved in ethanol to form a benzoin dimethyl ether solution and a benzophenone solution with a concentration of 20 - 50 mg / mL. Rapamycin and sirolimus are dissolved in dimethyl sulfoxide to form a rapamycin solution and a sirolimus solution with a concentration of 10 - 30 mg / mL. Heparin is dissolved in physiological saline to prepare a heparin solution with a concentration of 50 - 100 mg / mL. Urokinase is dissolved in a Tris-HCl buffer at pH 7.2 - 7.4 to form a urokinase solution with a concentration of 20 - 50 mg / mL;

[0097] S2. Mixing: Then, the collagen solution and the fibronectin solution are mixed in a sterile container by weight. Using a magnetic stirrer, stir at a speed of 100 - 200 rpm for 10 - 15 minutes, then add the benzoin dimethyl ether solution and the benzophenone solution, increase the stirring speed to 300 - 400 rpm, and stir for 20 - 30 minutes. Then add the rapamycin solution and the sirolimus solution, continue to stir for 20 - 30 minutes, and keep the stirring speed at 300 - 400 rpm. Then add the heparin solution and the urokinase solution, and stir at a speed of 400 - 500 rpm for 30 - 45 minutes. During the stirring process, the entire container needs to be placed in an environment of 4 - 8°C to form a drug gel solution;

[0098] S3. Molding: Then, the drug gel solution is injected into a sterile mold and frozen at -20°C for 2 - 4 hours to form a drug gel.

[0099] Example 5:

[0100] The difference between this example and Example 4 above is that:

[0101] The drug gel comprises the following raw materials in parts by weight: 30 parts of collagen, 15 parts of fibronectin, 5 parts of benzoin dimethyl ether, 3 parts of benzophenone, 10 parts of rapamycin, 8 parts of sirolimus, 12 parts of heparin, and 8 parts of urokinase.

[0102] Example 6:

[0103] The difference between this example and Example 4 above is that:

[0104] The drug gel comprises the following raw materials in parts by weight: 35 parts of collagen, 20 parts of fibronectin, 7.5 parts of benzoin dimethyl ether, 5.5 parts of benzophenone, 12.5 parts of rapamycin, 10 parts of sirolimus, 16 parts of heparin, and 11.5 parts of urokinase.

[0105] Table 2:

[0106]

[0107] The comparison in the above table is with a traditional drug gel. It can be seen from Table 2 that different amounts of collagen, fibronectin, benzoin dimethyl ether, benzophenone, rapamycin, zotarolimus, heparin, and urokinase can affect the elastic modulus of the drug gel, the adhesion area of adherent cells, and the cell proliferation rate, thereby affecting the stability and therapeutic effect of the drug gel, enhancing the performance of the drug gel in the complex in vivo environment, achieving precise regulation of drug release and cell behavior through light irradiation, ensuring the precise onset of the drug at the lesion site, and improving the precision of the therapeutic effect.

[0108] Although the embodiments of the present invention have been shown and described, for those of ordinary skill in the art, it can be understood that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A drug delivery device for treating aortic dissection based on a double-layer balloon, comprising an outer balloon (1), characterized in that: The outer wall of the outer balloon (1) is provided with a blood vessel repair coating (2), one side of the outer balloon (1) is evenly provided with an injection structure (3), a catheter structure is fixedly provided in the middle of the outer balloon (1), a catheter seat (5) is fixedly provided at one end of the catheter structure, an inner balloon (6) is fixedly provided at the other end of the catheter structure, the inner balloon (6) is located inside the outer balloon (1), a drug gel (17) is provided between the inner balloon (6) and the outer balloon (1), and a medical protective cover (8) is provided inside the catheter structure. The medical protective sleeve (8) is fixedly connected to a cladding sleeve (11) inside, and an optical fiber (12) is fixedly connected to the cladding sleeve (11) inside. A microlens (7) is fixedly provided at one end of the optical fiber (12). The microlens (7) is located inside the inner balloon (6). The microlens (7) is used to emit light to the blood vessel repair coating (2) and the drug gel (17). The blood vessel repair coating (2) is used to undergo an activation reaction under the action of light, and the drug gel (17) is used to undergo an activation reaction and adhesive fixation under the action of light.

2. The drug delivery device for treating aortic dissection based on a double-layer balloon according to claim 1, characterized in that: The catheter structure comprises a first catheter (4), a fourth catheter (18) is evenly arranged on the outer wall of the first catheter (4), a second catheter (9) is arranged inside the first catheter (4), a third catheter (10) is arranged inside the second catheter (9), and one end of the first catheter (4), the second catheter (9), and the third catheter (10) is fixedly arranged on one side of a catheter seat (5).

3. The drug delivery device for treating aortic dissection based on a double-layer balloon according to claim 2, characterized in that: The other ends of the second catheter (9) and the third catheter (10) are fixedly arranged in the middle of the inner balloon (6), and the other end of the first catheter (4) is fixedly arranged in the middle of the outer balloon (1). A one-way valve (16) is arranged between the first catheter (4) and the second catheter (9), and the one-way valve (16) is located inside one end of the first catheter (4).

4. The drug delivery device for treating aortic dissection based on a double-layer balloon according to claim 2, characterized in that: The fourth catheter (18) is used to guide the blood circulation in the aorta, the gap between the second catheter (9) and the third catheter (10) is connected to the interior of the inner balloon (6), and the gap between the first catheter (4) and the second catheter (9) is connected to the gap between the outer balloon (1) and the inner balloon (6).

5. The drug delivery device for treating aortic dissection based on a double-layer balloon according to claim 1, characterized in that: The interior of the injection structure (3) is connected to the interior of the outer balloon (1), a cavity (15) is provided in the middle of the catheter seat (5), the interior of the cavity (15) is connected to the interior of the third catheter (10), and one side of the medical protective cover (8) is provided inside the third catheter (10).

6. The drug delivery device for treating aortic dissection based on a double-layer balloon according to claim 1, characterized in that: The interior of the catheter seat (5) is uniformly provided with a first balloon filling port (13), the interior of the first balloon filling port (13) is connected to the gap between the second catheter (9) and the third catheter (10), and the interior of the catheter seat (5) is uniformly provided with a second balloon filling port (14), the interior of the second balloon filling port (14) is connected to the gap between the first catheter (4) and the second catheter (9).

7. A vascular repair coating, characterized in that: A double-layer balloon-based drug delivery device for treating aortic dissection as described in any one of claims 1 to 6, comprising the following raw materials in parts by weight: 15-25 parts of vascular endothelial growth factor, 10-20 parts of fibroblast growth factor, 15-25 parts of pentaerythritol tetraacrylate, 10-20 parts of tripropylene glycol diacrylate, 30-45 parts of chitosan, and 25-40 parts of hyaluronic acid.

8. A method for preparing a vascular repair coating, characterized in that: The vascular repair coating according to claim 7 comprises the following steps: S1. Raw material pretreatment: dissolving vascular endothelial growth factor in a phosphate buffer at 4°C containing 0.1% bovine serum albumin to prepare a vascular endothelial growth factor solution with a concentration of 1-5 mg / mL, dissolving fibroblast growth factor in PBS containing 0.1% human serum albumin to prepare a fibroblast growth factor solution with a concentration of 1-5 mg / mL, respectively preparing pentaerythritol tetraacrylate and tripropylene glycol diacrylate with acetone to prepare pentaerythritol tetraacrylate solution and tripropylene glycol diacrylate solution with a concentration of 50-100 mg / mL, dissolving chitosan in 1% acetic acid solution to adjust the chitosan solution to a concentration of 50-100 mg / mL, and stirring until transparent, dissolving hyaluronic acid in deionized water to prepare a hyaluronic acid solution with a concentration of 50-100 mg / mL; S2, solution mixing: then add vascular endothelial growth factor solution and fibroblast growth factor solution to a sterile container by weight, stir at a speed of 100-200 rpm on a magnetic stirrer for 10-15 minutes, then add pentaerythritol tetraacrylate solution and tripropylene glycol diacrylate solution, increase the stirring speed to 300-400 rpm, continue stirring for 20-30 minutes, then add chitosan solution and hyaluronic acid solution, stir at a speed of 400-500 rpm for 30-45 minutes to form a uniform mixed solution, and during the stirring process, the container is placed in an ice bath; S3, solution coating: immerse the outer balloon (1) in the mixed solution, pull it up at a speed of 5-10 cm / min, so that the coating is evenly coated on its surface, repeat the dipping 2-3 times, and place it in a fume hood after each dipping; S4. Photocuring: irradiate the coated outer balloon (1) with an ultraviolet light source with a wavelength of 400-500 nm, and control the light intensity at 20-50 mW / cm 2 The irradiation time is 60-120 seconds, so that the photoinitiator cross-linking agent triggers a cross-linking reaction to form a vascular repair coating.

9. A pharmaceutical gel, characterized in that: A double-layer balloon-based aortic dissection treatment drug delivery device as described in any one of claims 1 to 6, comprising the following raw materials in parts by weight: 30-40 parts of collagen, 15-25 parts of fibronectin, 5-10 parts of dimethyl benzoate, 3-8 parts of benzophenone, 10-15 parts of rapamycin, 8-12 parts of zotarolimus, 12-20 parts of heparin, and 8-15 parts of urokinase.

10. A method for preparing a drug gel, characterized in that: The pharmaceutical gel according to claim 9 comprises the following steps: S1. Pretreatment: Dissolve collagen in a 0.05M acetic acid solution at 4°C by stirring to prepare a collagen solution with a concentration of 50-100 mg / mL; dissolve fibronectin in PBS containing 0.1% human serum albumin to prepare a fibronectin solution with a concentration of 20-50 mg / mL; dissolve benzoin dimethyl ether and benzophenone in ethanol to prepare a benzoin dimethyl ether solution and a benzophenone solution with a concentration of 20-50 mg / mL, respectively; dissolve rapamycin and zotarolimus in dimethyl sulfoxide to prepare a rapamycin solution and a zotarolimus solution with a concentration of 10-30 mg / mL; dissolve heparin in physiological saline to prepare a heparin solution with a concentration of 50-100 mg / mL; and dissolve urokinase in a Tris-HCl buffer at pH 7.2-7.4 to prepare a urokinase solution with a concentration of 20-50 mg / mL; S2, mixing: then the collagen solution and the fibronectin solution are mixed in a sterile container by weight, and stirred at a speed of 100-200 rpm for 10-15 minutes using a magnetic stirrer, and then the benzoin dimethyl ether solution and the benzophenone solution are added, and the stirring speed is increased to 300-400 rpm, and stirred for 20-30 minutes, and then the rapamycin solution and the zotarolimus solution are added, and the stirring is continued for 20-30 minutes, and the stirring speed is maintained at 300-400 rpm, and then the heparin solution and the urokinase solution are added, and stirred at a speed of 400-500 rpm for 30-45 minutes, and during the stirring process, the entire container needs to be placed in an environment of 4-8°C, so as to form a drug gel solution; S3, molding: The drug gel solution is then injected into a sterile mold and frozen at -20°C for 2-4 hours to mold it into a drug gel.

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