Fiber-optic-containing arteriovenous catheter device for image-guided navigation of interventional delivery of photosensitizers

Abstract

The application discloses a kind of optical fiber-containing arteriovenous catheter device for interventional delivery of photosensitizer under image navigation, comprising: catheter body, with the distal end of arteriovenous blood vessel insertable and the proximal end located outside the body;Medicine delivery channel, along the axial direction of catheter body, for delivering photosensitizer to target blood vessel;Optical fiber channel, arranged in catheter body and independent of medicine delivery channel, for accommodating optical fiber assembly;Optical fiber assembly, arranged in optical fiber channel, with the distal end forming light outlet, for guiding laser into blood vessel to activate photosensitizer;Balloon, arranged outside the distal end of catheter body, balloon has independent filling cavity, filling cavity is communicated with balloon filling port arranged on catheter body, for filling to block blood flow before photosensitizer release.The application integrates image navigation, photosensitizer targeted delivery, laser activation and blood flow blocking functions, significantly improves the accuracy and efficiency of tumor vascular embolization, reduces operation steps and patient trauma.

Description

Technical Field

[0001] This invention belongs to the field of medical device technology, specifically relating to an arteriovenous catheter system that integrates image navigation and photosensitizer delivery. It is particularly suitable for embolization treatment of blood supply arteries for solid tumors, and can also be applied to hemostasis, treatment of varicose veins, and the construction of animal models of stroke or vascular stenosis. Background Technology

[0002] In the fields of interventional radiology and photodynamic therapy, the comprehensive treatment of solid tumors has always been a focus of clinical research. With the development of image-guided technology and precision medicine, interventional therapy is evolving towards minimally invasive, precise, and multifunctional integration. However, existing technologies still have significant limitations in terms of multimodal treatment synergy, device integration, and operational safety.

[0003] Photodynamic therapy (PDT), as an integrated treatment approach, is gaining increasing attention in fields such as cancer treatment. PDT involves delivering a photosensitizer to target tissue cells, followed by irradiation with a specific wavelength of laser light. This activates the photosensitizer, generating reactive oxygen species (ROS). Excessive ROS can cause oxidative damage to the mitochondria and DNA of cancer cells, thereby killing them. However, current methods of photosensitizer delivery have several limitations. Traditional photosensitizers are primarily delivered systemically via intravenous injection. This method makes it difficult to precisely concentrate the photosensitizer in diseased tissues, resulting in low concentrations at the lesion site, affecting the effectiveness of the photodynamic response and failing to cause sufficient damage to diseased cells. Furthermore, systemic administration may trigger phototoxic reactions, causing additional suffering and risks for patients.

[0004] In recent years, interventional targeted delivery of photosensitizers or drugs has become a research hotspot. For example, Chinese patent CN119971268A discloses a fiber optic balloon catheter, which loads drugs on the balloon surface and has a foldable or inflatable slow-flow component on the delivery side to reduce drug loss due to blood flow. After balloon expansion, a 400-500 nm laser is introduced via optical fiber to activate the photosensitizer, promoting cross-linking of vascular wall proteins to form a natural scaffold, thus combining the functions of expansion, drug loading, and photodynamic-support. In addition, Chinese patent CN221384913U proposes a treatment device for photodynamic therapy. Its core function is to achieve directional and uniform irradiation of light through the conical needle-like structure at the end of the optical fiber and the aspherical lens design of the sheath, thereby activating the photosensitizer pre-delivered to the local tissue via an interventional route to complete photodynamic therapy (PDT). However, PDT still faces several limitations in clinical application: First, the limited depth of light penetration into tissue restricts its therapeutic effect on deep tumors; second, solid tumors are often in a hypoxic state (oxygen partial pressure is often below 5 mmHg), far below the threshold required for PDT to generate ROS, resulting in a significant reduction in therapeutic efficacy; third, the immune and inflammatory responses induced by PDT have a "double-edged sword" nature, although appropriate acute inflammation can activate a systemic immune response, excessive reactions may lead to serious adverse reactions, and its regulation strategies are still immature; in addition, the high cost of treatment equipment and related consumables further restricts the widespread clinical application of PDT.

[0005] In summary, existing photosensitizer delivery technologies and photodynamic therapy strategies still have significant limitations, mainly including low delivery efficiency, insufficient targeting precision, limited tissue penetration, and significant systemic side effects. Therefore, there is an urgent need to develop a novel integrated arteriovenous catheter device capable of precise micro-delivery of photosensitizers, integrating real-time image-guided technology to improve treatment efficiency and reduce patient suffering. Summary of the Invention

[0006] The purpose of this invention is to provide an arteriovenous catheter device containing optical fibers for image-guided interventional delivery of photosensitizers. Through an integrated structural design, it aims to precisely deliver photosensitizers to tumor-supplying vessels or other diseased vessels. Laser activation of the photosensitizer induces intravascular embolization, blocking tumor blood supply to kill tumors, stop visceral bleeding, treat varicose veins, and create animal models of vascular embolization. This invention addresses problems in existing technologies such as insufficient drug delivery targeting, low embolization efficiency, severe invasiveness, and significant systemic side effects.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] An arteriovenous catheter device containing optical fibers for image-guided interventional delivery of photosensitizers, comprising:

[0009] The catheter body has a distal end that can be inserted into an artery or vein and a proximal end located outside the body;

[0010] A drug delivery channel, arranged along the axial direction of the catheter body, is used to deliver a photosensitizer to the target blood vessel;

[0011] An optical fiber channel, located within the catheter body and independent of the drug delivery channel, is used to house the optical fiber assembly.

[0012] An optical fiber assembly is disposed within the optical fiber channel, with its distal end forming a light outlet for introducing laser light into the blood vessel to activate the photosensitizer.

[0013] A balloon is disposed on the distal outer side of the catheter body. The balloon has an independent inflation chamber that communicates with the balloon inflation port disposed on the catheter body. It is used to inflate the balloon before the photosensitizer is released to block blood flow.

[0014] Furthermore, the arrangement of the drug delivery channel and the optical fiber channel is selected from any of the following:

[0015] Method 1: The catheter body includes an inner tube and an outer tube that are coaxially inserted. The inner tube has a cavity along its axial direction to form the drug delivery channel. The outer tube is sleeved outside the inner tube. An annular space is formed between the inner tube and the outer tube to form the optical fiber channel. Multiple solid quartz optical fibers or polymer optical fibers are evenly distributed in the annular space along the circumference. The distal ends of each optical fiber converge to form a tapered light guide and penetrate the distal end face of the outer tube to form the light outlet.

[0016] Method 2: The catheter body includes a first inner tube and a second inner tube arranged parallel and coaxially. The first inner tube has a cavity along its axial direction to form the drug delivery channel, and the second inner tube has a cavity along its axial direction to form the optical fiber channel. Multiple solid quartz optical fibers or polymer optical fibers are evenly distributed circumferentially in the cavity of the second inner tube. The distal ends of each optical fiber converge to form a tapered light guide and penetrate the distal end of the catheter body to form a light outlet. A gap of 0.1 mm to 0.2 mm is left between the first inner tube and the second inner tube.

[0017] Furthermore, in Method 1, the distal end of the inner tube extends 0.5mm to 2.0mm beyond the distal end face of the outer tube, and the extended distal end is hemispherical, with or without a cap.

[0018] Furthermore, in Method 1, the inner tube is provided with at least two lateral drug outlet holes on its distal sidewall, and a micro valve is provided at the drug outlet hole for releasing the photosensitizer at an adjustable flow rate of 0.1 to 2.0 mL / min under a pressure of 0.1 to 0.5 MPa.

[0019] Furthermore, in Method 2, the distal end of the first inner tube extends 0.5mm to 2.0mm beyond the distal end face of the second inner tube, and the extended distal end is hemispherical, with or without a cap.

[0020] Furthermore, in Method 2, the first inner tube is provided with a drug outlet at its distal end, and a micro valve is provided at the drug outlet for releasing the photosensitizer at an adjustable flow rate of 0.1 to 2.0 mL / min under a pressure of 0.1 to 0.5 MPa.

[0021] Furthermore, the fiber optic assembly also includes a diffusion lens fitted outside the tapered light guide portion. The diffusion lens is a concave lens or a Powell prism, used to adjust the emitted laser to a divergence angle of 15° to 60°.

[0022] Furthermore, the balloon is a compliant balloon with an outer diameter of 3mm to 12mm and a length of 10mm to 30mm after inflation, and the distal outer surface of the balloon is provided with a hydrophilic coating.

[0023] Furthermore, the proximal end of the drug delivery channel is provided with a Y-type connector, which communicates with the drug delivery channel and is equipped with a one-way valve to prevent backflow; the proximal end of the optical fiber channel is provided with a lead wire socket, and the proximal end of the optical fiber assembly is connected to a tunable laser via a quick-release connector. The output wavelength of the laser is 600±200nm, and the power is 0.2W~3.0W. The laser is also equipped with a foot switch to allow the surgeon to synchronously control the timing of illumination under image navigation; the photosensitizer is Bengal rose red or its derivatives, hypericin or its derivatives, or porphyrin-based photosensitizers.

[0024] Furthermore, the catheter body is a flexible tubular structure composed of three co-extruded tubular materials, consisting of a polytetrafluoroethylene layer, a stainless steel braided reinforcement layer, and a thermoplastic polyurethane outer layer from the inside out, with an outer diameter of 1.8mm to 3.0mm and an inner diameter of 1.0mm to 1.5mm. The outer surface of the catheter body is provided with multiple radiopaque markings distributed along its axial direction, with a spacing of 5mm, for precise positioning under X-ray fluoroscopy.

[0025] Beneficial effects: This invention significantly improves the accuracy and efficiency of tumor vascular embolization by integrating image navigation, photosensitizer targeted delivery, laser activation and blood flow blocking functions, reducing operation steps and patient trauma. It is applicable to vascular embolization treatment of solid tumors such as liver cancer and lung cancer, hemostasis of visceral bleeding, treatment of varicose veins, or preparation of animal vascular embolization models, etc.

[0026] Compared with the prior art, the present invention has the following advantages:

[0027] (1) Precise targeted delivery: By temporarily blocking blood flow with a balloon, the photosensitizer is prevented from spreading throughout the body with the blood flow, thereby achieving local high concentration enrichment of the photosensitizer in the target blood vessel and significantly reducing systemic phototoxic side effects.

[0028] (2) Integrated design: The three major functions of photosensitizer delivery, laser activation and vascular embolization are integrated into a single catheter device, which can complete the entire treatment process without changing the device, greatly reducing operation steps and patient trauma.

[0029] (3) Two structural designs: Two parallel implementation schemes are provided: inner tube + outer tube and double inner tube. Both can realize the independent setting of drug delivery channel and fiber optic channel without interference, adapting to different clinical scenarios and operating habits.

[0030] (4) Uniform and controllable illumination: The laser divergence angle is adjusted to 15° to 60° by using a diffusion lens (concave lens or Powell prism) to achieve uniform distribution of light energy in blood vessels and ensure full activation of photosensitizer; the foot switch, in conjunction with image navigation, enables precise control of the timing of illumination.

[0031] (5) High operational safety: The hemispherical design of the distal end of the inner tube and the control of the extension length (0.5-2.0mm) reduce mechanical damage to the vascular endothelium; the hydrophilic coating reduces the resistance of balloon retraction and reduces traction damage to the vascular wall; and the non-transmissive marking enables precise intraoperative positioning.

[0032] (6) Wide range of applications: It is not only applicable to vascular embolization treatment of solid tumors such as liver cancer and lung cancer, but also to hemostasis of visceral bleeding, treatment of varicose veins, and construction of animal vascular embolization models for research on ischemic diseases, screening of therapeutic drugs and evaluation of interventional device performance. Attached Figure Description

[0033] Figure 1 This is an overall appearance view of the device of the present invention;

[0034] Figure 2 Figure A is a front view of the device of the present invention, wherein Figure B is a schematic diagram of the inner tube + outer tube structure with a cap at the far end; Figure C is a schematic diagram of the inner tube + outer tube structure without a cap at the far end; and Figure D is a schematic diagram of the double inner tube structure.

[0035] Figure 3 This is a cross-sectional structural diagram of the distal region of the device of the present invention, wherein Figure A shows the inner tube + outer tube structure, and Figure B shows a schematic diagram of the double inner tube structure;

[0036] Figure 4 The diagrams are schematic diagrams of the intravascular working state of the device of the present invention, wherein Figure A is a schematic diagram of the inner tube + outer tube structure; and Figure B is a schematic diagram of the double inner tube structure.

[0037] Figure 5This is a schematic diagram illustrating an embodiment of the device of the present invention in the blood vessels of a living rabbit ear;

[0038] In the diagram: 1-Catheter body, 2-Fiber optic assembly, 3-Balloon, 4-Y-connector, 5-Inner tube, 6-Outer tube, 7-First inner tube, 8-Second inner tube, 9-Gap, 10-Leader socket, 11-Quick-release connector, 12-Tunable laser, 13-Balloon filling port, 14-Fiber optic cable, 15-Conical light guide, 16-Guide wire inlet / outlet, 17-Drug delivery channel, 18-Non-transmissive marker, 19-Guide wire, 20-Lateral drug outlet, 21-Cap, 22-End drug outlet, 23-Epoxy resin, 24-Annular space. Detailed Implementation

[0039] The technical solutions in the embodiments of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are merely some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0040] The present invention provides a fiber optic arteriovenous catheter device for image-guided interventional delivery of photosensitizers, the specific structure of which is as follows:

[0041] (a) Catheter body

[0042] The catheter body 1 is a flexible tubular structure that can be inserted into arteries and veins. It is made of three layers of medical co-extruded tubing, consisting of a polytetrafluoroethylene (PTFE) inner layer, a stainless steel braided reinforcement layer, and a thermoplastic polyurethane (TPU) outer layer from the inside out. The PTFE inner layer reduces drug delivery resistance and vascular endothelial damage; the stainless steel braided reinforcement layer improves anti-kinking performance and delivery force, ensuring smooth arrival at the target artery or vein in complex vascular pathways; and the TPU outer layer has good biocompatibility and flexibility, reducing friction and irritation to the vascular wall.

[0043] The catheter body 1 has an overall outer diameter of 1.8–3.0 mm and an inner diameter of 1.0–1.5 mm. The diameter of the catheter increases accordingly for veins. The distal end has a tapered transition structure to facilitate puncture and intravascular advancement. The proximal end is located outside the body and has multiple interfaces for connecting to external devices. Multiple radiopaque markers 18 (such as platinum-iridium alloy rings) are distributed axially on the outer surface, spaced 5 mm apart, which can accurately locate the distal end of the catheter under X-ray fluoroscopy to ensure precise access to the target vascular branch.

[0044] (ii) Combination structure of inner tube and outer tube (or double inner tube)

[0045] Both designs have independently set up drug delivery channel 17 and fiber optic channel to avoid mutual interference and ensure that photosensitizer delivery and laser transmission do not affect each other.

[0046] First design (inner tube + outer tube):

[0047] The inner tube 5 is coaxially inserted within the catheter body 1, using the same three-layer co-extruded material as the catheter body 1. It has an axially extending cavity, namely the drug delivery channel 17 (inner diameter can be 0.5–0.8 mm), for delivering the photosensitizer. The distal end of the inner tube 5 extends 0.5 mm–2.0 mm beyond the distal end face of the outer tube 6, and the extended end is hemispherical to reduce mechanical damage to the vascular endothelium; the distal end may or may not have a cap 21. The distal sidewall of the inner tube 5 has at least two lateral drug outlet holes 20 (diameter can be 0.2–0.5 mm). Microvalves (made of shape memory alloy) can be integrated at these outlet holes to release the photosensitizer at an adjustable flow rate of 0.1–2.0 mL / min under a pressure of 0.1–0.5 MPa, opening only after reaching the target blood vessel to avoid premature leakage. A Y-type connector 4 is located at the proximal end of the inner tube 5, with a built-in one-way valve to prevent drug backflow and ensure accurate dosage.

[0048] The outer tube 6 is fitted outside the inner tube 5, forming an annular space 24 (the width of which can be 0.3 to 0.8 mm) with the inner tube 5, serving as a channel for accommodating the fiber optic assembly 2. The distal end of the outer tube 6 smoothly transitions to the hemispherical end of the inner tube 5 to avoid obstruction within the blood vessel; a lead wire seat 10 is provided at the proximal end to fix the fiber optic assembly 2 and connect it to an external laser device.

[0049] Second design (double inner tube):

[0050] The first inner tube 7 functions identically to the inner tube 5 in the first design. The distal end of the first inner tube 7 extends 0.5mm to 2.0mm beyond the distal end face of the second inner tube 8, and its hemispherical shape reduces mechanical damage to the vascular endothelium. A cap may or may not be provided at the distal end. The first inner tube 7 has a drug outlet 22 at its distal end for delivering photosensitizer. Parameters such as microvalve performance and the design of the Y-connector 4 are identical to those of the inner tube in the inner tube + outer tube device.

[0051] The second inner tube 8 is parallel and coaxially inserted into the main body of the conduit 1. Its cavity (with an inner diameter of 0.3 to 0.8 mm) encloses the optical fiber 14, replacing the annular space 24. A small gap 9 of 0.1 mm to 0.2 mm is left between the first inner tube 7 and the second inner tube 8. A lead wire seat 10 is provided at the proximal end to ensure a stable connection between the optical fiber 14 and the laser source.

[0052] (III) Fiber Optic Assembly

[0053] Fiber optic component 2 is used to guide laser light into the target blood vessel, activating a photosensitizer to induce vascular embolism, specifically including:

[0054] Optical fiber body: Multiple solid silica optical fibers 14 are used, evenly distributed circumferentially in the annular space 24 (first design) or the cavity of the second inner tube 8 (second design). The silica optical fiber 14 has low optical loss (transmission efficiency >90%), high mechanical strength, and good biocompatibility. Its outer diameter can be 0.1–0.3 mm, allowing it to adapt to the bending path of the guide tube. Another alternative is polymer optical fiber.

[0055] Conical light guide 15: The distal ends of each optical fiber 14 converge and fuse to form a conical light guide 15 (the cone angle can be 15° to 30°), which penetrates the distal end face of the outer tube 6 (or the catheter body 1) to form a light outlet, reducing light reflection loss and ensuring that the laser energy is concentrated in the target blood vessel.

[0056] Diffusion lens: Fitted outside the tapered light guide 15, using a concave lens or Powell prism structure, the divergence angle of the emitted laser is adjusted to 15°~60°, so that the laser energy is evenly distributed in the blood vessel (energy deviation <10%), ensuring full activation of the photosensitizer.

[0057] Connection components: The proximal end of the fiber optic assembly 2 connects to the tunable laser 12 via a quick-release connector 11. The connector features a snap-fit ​​design, allowing for installation and removal within 3 seconds, and includes a mis-insertion prevention structure. The tunable laser 12 outputs a wavelength of 600±200nm (matching the photosensitizer absorption peak), with a power range of 0.2~3.0W. It supports continuous wave or pulsed modes and is equipped with a foot switch, facilitating operator control of illumination timing under image-guided guidance for precise activation of the photosensitizer within the blood vessel.

[0058] (iv) Balloon

[0059] Balloon 3 is positioned distal to the outer side of catheter body 1. If necessary, it can block blood flow to the target vessel before photosensitizer delivery, prevent photosensitizer reflux, increase local photosensitizer concentration, and enhance the embolization effect. Its structural features include:

[0060] Materials and morphology: Adaptable materials (such as polyamide elastomer) are used, with a thickness of <0.1mm when unfilled, which fits tightly against the outer wall of the catheter body 1; after filling, it is cylindrical with an outer diameter of 3-12mm (to adapt to different blood vessel diameters) and a length of 10-30mm to ensure complete blockage of tumor blood supply.

[0061] Inflation system: The balloon 3 has an independent inflation chamber, which is connected to an external syringe through the balloon inflation port 13 on the outer tube 6 (or the catheter body 1) to inject contrast agent (such as iohexol) or normal saline at a pressure of 1.0 atm to 3.0 atm, making the operation convenient.

[0062] Surface treatment: The distal outer surface is coated with a hydrophilic coating (such as polyvinylpyrrolidone) to reduce the coefficient of friction by more than 50% during retraction and reduce traction damage to the blood vessel wall.

[0063] (V) Collaborative Working Principle

[0064] The device achieves the treatment of tumors, varicose veins, and bleeding, or the preparation of animal vascular embolization models, through a process of "blocking blood flow - delivering photosensitizer - laser activation - vascular embolization".

[0065] Under image-guided navigation, the distal end of the catheter body 1 is pushed to the target blood vessel, and the position is confirmed under image-guided navigation.

[0066] If necessary, contrast agent (such as iohexol) or normal saline is injected through the balloon inflation port 13 to inflate balloon 3 and block blood flow, preventing photosensitizer from spreading to other blood vessels with the blood flow;

[0067] The photosensitizer is injected through the Y-type connector 4 of the inner tube 5 (or the first inner tube 7), the micro valve is opened, and the drug is released into the target blood vessel through the lateral drug outlet 20 or the end drug outlet 22.

[0068] The tunable laser 12 is activated, and the laser is transmitted to the tapered light guide 15 through the fiber optic assembly 2. The laser is uniformly irradiated into the photosensitizer in the blood vessel through the diffusion lens, which activates the photosensitizer and causes a photochemical reaction, which stimulates the coagulation mechanism and forms embolic substances to block the target blood vessel.

[0069] After embolization, the pressure of balloon 3 is released to retract it, and the catheter body 1 is withdrawn to achieve permanent occlusion of tumor vessels, blocking the blood supply to the tumor to kill the tumor; bleeding stops; varicose veins are embolized; and ischemic models of animal organs are established.

[0070] Combination Figures 1 to 4 The device structure and operating state of the present invention are further illustrated below:

[0071] Figure 1 The overall structure of the arteriovenous catheter device is shown, including the relative positions and overall shape of the catheter body, balloon, Y-type connector, balloon filling port, etc.

[0072] Figure 2 The device structure is presented from a frontal view, clearly showing the coaxial arrangement of the inner and outer tubes, and the position of the balloon on the distal outer side of the catheter body. Figure A shows a schematic diagram of the inner and outer tube arteriovenous catheter device with a cap at the distal end; Figure B shows a schematic diagram of the inner and outer tube arteriovenous catheter device without a cap at the distal end; Figure C is a schematic diagram of the dual inner tube arteriovenous catheter device, showing the parallel coaxial arrangement of the first and second inner tubes.

[0073] Figure 3This is a cross-sectional structural diagram of the distal region of the device of the present invention, showing the internal structure of the cavity of the inner tube, the annular space between the inner tube and the outer tube, the optical fiber assembly in the annular space, and the specific structure of the tapered light guide and the diffusion lens at the distal light outlet; in addition, it also includes a comparative illustration of different types of optical fibers (such as dot fiber, nested fiber, ring fiber, double ring fiber, and diffusion fiber).

[0074] Figure 4 This diagram illustrates the intravascular operation of the device, including scenarios such as balloon inflation to block blood flow, photosensitizer application to target tissue, and laser irradiation, as well as its positional relationship with adjacent branch vessels. Figure A shows the intravascular operation of an arteriovenous catheter device with an inner and outer tubing structure; Figure B shows the intravascular operation of an arteriovenous catheter device with a double inner tubing structure.

[0075] The following examples use rabbit ear arteries to test the vascular embolism model prepared by the device of the present invention to verify the principle.

[0076] This embodiment utilizes the device of the present invention to construct a rabbit ear artery embolism model, simulating the pathological state of vascular stenosis or occlusion. This model can be used for research on the mechanisms of ischemic diseases, screening of therapeutic drugs, and performance evaluation of interventional devices. The specific operation is as follows:

[0077] Model preparation

[0078] Experimental animals: Healthy New Zealand white rabbits, weighing 2.5 kg–3.0 kg, of any sex, were selected; they were fasted for 12 hours before the procedure but had free access to water. Anesthesia was administered via the marginal ear vein using a 3% sodium pentobarbital solution at a dose of 30 mg / kg. After anesthesia, the animals were secured in a rabbit stand, both ears were exposed, shaved, and routinely disinfected. The rabbit ear's vascular anatomy is clear, the procedure is simple, and real-time observation is convenient, making it an ideal site for constructing a vascular embolization model.

[0079] Instrument configuration: The arteriovenous catheter device adopts the first design method of this invention (inner tube + outer tube structure), and is adapted and adjusted according to the diameter of the central artery of rabbit ear (approximately 0.8-1.2 mm): the outer diameter of the catheter body is 1.8 mm, the inner diameter is 1.0 mm, and the distal end has a gradually tapered transition structure; the distal end of the inner tube is provided with a drug outlet with a diameter of 0.2 mm, and the micro-valve at the drug outlet is set with an opening pressure of 0.2 MPa and a flow rate adjustment range of 0.3-0.8 mL / min; it is equipped with a tunable laser with an output wavelength of 532 nm±5 nm and a power of 200 mW, as well as conventional interventional surgical instruments.

[0080] Reagent preparation: Prepare an aqueous solution of Rose Bengal photosensitizer with a concentration of 3 mg / mL, and store it in the dark for later use; prepare physiological saline as a control reagent.

[0081] Following the central auricular artery on the dorsal side of the rabbit ear, temporarily occlude the proximal blood flow with a vascular clamp 2 cm from the ear root. Using the Seldinger technique, insert the distal end of the catheter body into the vessel lumen via arterial puncture and slowly advance it along the vessel lumen, reaching approximately 1 cm anterior to the distal branch of the central auricular artery, ensuring precise positioning of the target vessel segment. Continuously flush the lumen with saline during catheter advancement to prevent blood reflux and thrombus formation.

[0082] After confirming the catheter is correctly positioned, connect the proximal Y-connector of the inner tube to the microinfusion pump and slowly inject the Bengal rose red photosensitizer aqueous solution. The microvalve opens at 0.2 MPa pressure, releasing the drug at a flow rate of 0.5 mL / min through the distal outlet of the inner tube into the target segment of the central auricular artery. The total dosage is 0.3-0.5 mL, calculated based on the length and diameter of the target vessel, ensuring uniform diffusion of the drug within the local blood vessel. Observe the color change within the blood vessel during administration; the photosensitizer will turn red, confirming that the target vessel segment has been filled with the drug.

[0083] After the photosensitizer delivery was completed, the surgeon activated the tunable laser at a wavelength of 532 nm, a power of 0.2 W, in continuous wave mode. The laser light was transmitted through an optical fiber assembly to the tapered light guide, and the irradiation time was 4 minutes. Under 532 nm laser excitation, the photosensitizer underwent a photochemical reaction: Bengal rose red absorbed photons and produced singlet oxygen (…). 1 O2 and other reactive oxygen species (ROS). Excessive ROS induce lipid peroxidation, protein cross-linking, and DNA damage in vascular endothelial cells, leading to endothelial cell necrosis and shedding. This exposes subendothelial collagen, activates platelet aggregation, and initiates a coagulation cascade, ultimately forming a red thrombus composed mainly of fibrin-encapsulated erythrocytes, completely obstructing the vascular lumen (see [link to article]). Figure 5 ).

[0084] Five minutes after laser irradiation, the vascular status was observed in real time using a light microscope: In the control group (saline ear artery administration + laser irradiation group), blood flow was unobstructed throughout the entire course of the blood vessels, with no signs of congestion or occlusion. Figure 5 In the experimental group (Bangladesh rose otolith administration via ear artery + laser irradiation), blood flow interruption occurred after 5 minutes of irradiation, and significant purple ecchymosis was observed on the second day due to vascular occlusion. Figure 5 (A′) On the second day after laser irradiation, the ear artery in the control group appeared normal red, with no abnormal skin temperature, uniform auricle color, clear arterial course, and no signs of thrombosis. Figure 5 (B) In the experimental group, a stable occlusive thrombus had formed. The skin temperature in the ischemic area was about 5°C lower on average than that in the saline control group. The auricle showed obvious cyanosis, and the target artery area appeared dark red to purplish-black, indicating that the intravascular thrombus formation was stable and blood flow was completely blocked. Figure 5(B′). Pathological examination of the rabbit ear intervention segment tissue was performed. HE staining results showed that the control group had normal lumen morphology, normal and continuous endothelial cell morphology, and intact intima, media, and adventitia structures, with no thrombosis or inflammatory damage. Figure 5 (C, D); In the experimental group, the blood vessel lumen was filled with dense red thrombus, composed of an eosinophilic fibrin network, a large number of red blood cells and a small number of white blood cells. The arterial intima endothelial cells were necrotic and sloughed off, the vessel wall was edematous and accompanied by focal inflammatory infiltration, and the arterial lumen was occluded, which is consistent with the characteristics of acute thrombosis. Figure 5 (C′, D′). Figure 5 In the diagram, A, B, C, and D represent the saline auricular artery administration + laser irradiation group (control group); A′, B′, C′, and D′ represent the Bengal rose auricular artery administration + laser irradiation group (experimental group). The scale bar is 1.0 cm.

[0085] Besides verifying the working principle of the invention and suggesting numerous clinical applications, the embolization model has the following applications: a) screening of drugs for neurological function repair after ischemic stroke; b) performance testing of interventional devices for vascular recanalization and research on the mechanism of embolization treatment. This device allows for precise control of the embolization site and extent, improving the model's uniformity and reproducibility.

[0086] This embodiment verifies the effectiveness of the device of the present invention in precise vascular embolization and animal model construction, demonstrating the advantages of the device in precise delivery, efficient activation, and safe operation. In practical applications, parameters such as catheter size, photosensitizer type, and laser parameters can be adjusted according to treatment or research goals to meet different needs.

[0087] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A fiber-optic arteriovenous catheter device for image-guided interventional delivery of photosensitizers, characterized in that, include: The catheter body has a distal end that can be inserted into an artery or vein and a proximal end located outside the body; A drug delivery channel, arranged along the axial direction of the catheter body, is used to deliver a photosensitizer to the target blood vessel; An optical fiber channel, located within the catheter body and independent of the drug delivery channel, is used to house the optical fiber assembly. An optical fiber assembly is disposed within the optical fiber channel, with its distal end forming a light outlet for introducing laser light into the blood vessel to activate the photosensitizer. A balloon is disposed on the distal outer side of the catheter body. The balloon has an independent inflation chamber that communicates with the balloon inflation port disposed on the catheter body. It is used to inflate the balloon before the photosensitizer is released to block blood flow.

2. The apparatus according to claim 1, characterized in that, The arrangement of the drug delivery channel and the optical fiber channel is selected from any of the following: Method 1: The catheter body includes an inner tube and an outer tube that are coaxially inserted. The inner tube has a cavity along its axial direction to form the drug delivery channel. The outer tube is sleeved outside the inner tube. An annular space is formed between the inner tube and the outer tube to form the optical fiber channel. Multiple solid quartz optical fibers or polymer optical fibers are evenly distributed in the annular space along the circumference. The distal ends of each optical fiber converge to form a tapered light guide and penetrate the distal end face of the outer tube to form the light outlet. Method 2: The catheter body includes a first inner tube and a second inner tube arranged parallel and coaxially. The first inner tube has a cavity along its axial direction to form the drug delivery channel, and the second inner tube has a cavity along its axial direction to form the optical fiber channel. Multiple solid quartz optical fibers or polymer optical fibers are evenly distributed circumferentially in the cavity of the second inner tube. The distal ends of each optical fiber converge to form a tapered light guide and penetrate the distal end of the catheter body to form a light outlet. A gap of 0.1 mm to 0.2 mm is left between the first inner tube and the second inner tube.

3. The apparatus according to claim 2, characterized in that, In Method 1, the distal end of the inner tube extends 0.5mm to 2.0mm beyond the distal end face of the outer tube, and the extended distal end is hemispherical. The distal end may or may not be covered.

4. The apparatus according to claim 2 or 3, characterized in that, In Method 1, the inner tube has at least two lateral drug outlet holes on its distal sidewall, and a micro valve is provided at the drug outlet hole for releasing photosensitizer at an adjustable flow rate of 0.1 to 2.0 mL / min under a pressure of 0.1 to 0.5 MPa.

5. The apparatus according to claim 2, characterized in that, In Method 2, the distal end of the first inner tube extends 0.5mm to 2.0mm beyond the distal end face of the second inner tube, and the extended distal end is hemispherical. The distal end may or may not be covered.

6. The apparatus according to claim 2 or 5, characterized in that, In Method 2, the first inner tube is provided with a drug outlet at its distal end, and a micro valve is provided at the drug outlet for releasing the photosensitizer at an adjustable flow rate of 0.1 to 2.0 mL / min under a pressure of 0.1 to 0.5 MPa.

7. The apparatus according to claim 1, characterized in that, The fiber optic assembly also includes a diffusion lens fitted outside the tapered light guide section. The diffusion lens is a concave lens or a Powell prism, used to adjust the emitted laser to a divergence angle of 15° to 60°.

8. The apparatus according to claim 1, characterized in that, The balloon is a compliant balloon with an outer diameter of 3mm to 12mm and a length of 10mm to 30mm after inflation, and the distal outer surface of the balloon is provided with a hydrophilic coating.

9. The apparatus according to claim 1, characterized in that, The drug delivery channel has a Y-type connector at its proximal end, which communicates with the drug delivery channel and is equipped with a one-way valve to prevent backflow. The fiber optic channel has a lead wire socket at its proximal end, and the fiber optic assembly is connected to a tunable laser via a quick-release connector. The laser has an output wavelength of 600±200nm and a power of 0.2W to 3.0W. The laser is equipped with a foot switch to allow the surgeon to synchronously control the timing of illumination under image navigation. The photosensitizer is Bengal rose red or its derivatives, hypericin or its derivatives, or porphyrin-based photosensitizers.

10. The apparatus according to claim 1, characterized in that, The catheter body is a flexible tubular structure composed of three co-extruded tubular materials, consisting of a polytetrafluoroethylene layer, a stainless steel braided reinforcement layer, and a thermoplastic polyurethane outer layer from the inside out. The outer diameter is 1.8mm to 3.0mm, and the inner diameter is 1.0mm to 1.5mm. The outer surface of the catheter body is provided with multiple radiopaque marks distributed along its axial direction, with a spacing of 5mm, for precise positioning under X-ray fluoroscopy.

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